Title of Invention

COSMETIC COMPOSITIONS COMPRISING A CYCLODIPEPTIDE COMPOUND

Abstract

An antiperspirant composition comprising: i) an antiperspirant active material ii) a continuous phase which comprises water-immiscible liquid carrier, and iii) a structurant therein which comprises a cyclodipeptide derivative, hereinafter DOPAD, having II the general formula in which RA represents a carbocyclic or heterocyclic group containing not more than; 2 rings, other than II unsubstituted cyclohexyl.

Full Text

FORM -2 THE PATENTS ACT, 1970 (39 of 1970) COMPLETE SPECIFICATION (See Section 10) COSMETIC COMPOSITIONS COMPRISING A CYCLODIPEPTIDE COMPOUND HINDUSTAN LEVER LIMITED, a company incorporated under the slndian Companies Act, 1913 and having its registered office at Hindustan Lever House, 165/166, Backbay Reclamation, Mumbai -400 020, Maharashtra, India The following specification particularly describes the nature of the invention and the manner in which it is to be performed. WO 03/059307 PCT/EP02/I4525 COSMETIC COMPOSITIONS COMPRISING A CYCLODIPEPTIDE COMPOUND FIELD OF THE INVENTION \ The present invention relates to cosmetic compositions for application to human skin, to the preparation and use of such compositions and to structurants for incorporation in such compositions and their preparation. 10 BACKGROUND OF THE INVENTION AND SUMMARY OF PRIOR ART 15 20 A wide var'iety of cosmetic compositions for application to human skin make use of a structured liquid carrier to deliver colour or some other active material to the surface of the skin. Significant examples of such cosmetic compositions include antiperspirant or deodorant compositions which are widely used in order to enable their users to avoid or minimise wet patches on their skin, especially emission of 'in axillary regions or to control or prevent the malodours, which could otherwise arise when the user perspires. Other examples of cosmetic compositions include lipsticks. Although structuring is a term that has often been employed 25 in respect of materials which structure a carrier liquid, I1 various othejr terms have been employed alternatively, including solidifying and gelling. Antiperspirant or deodorant formulations have been provided 30 with a range of different product forms. One of these is a so-called "stick" which is usually a bar of an apparently WO 03/059307 PCT/EP02/14525 firm solid material held within a dispensing container and which retains being applied its structural integrity and shape whilst In that respect they are representative, of cosmetic comp'ositions in stick form containing other active constituents. When a portion of the stick is drawn across the skin surface, a film of the stick composition is transferred to the skin surface. Although the stick has the appearance of a solid article capable of retaining its own shape for a period of time, the material often has a structured liquid phase so that a film of the composition is readily transferred from the stick to another surface upon contact. Antiperspirant Suspension sti sticks can be divided into three categories. rks contain a particulate antiperspirant active material suspended in a structured carrier liquid phase which often is anhydrous and/or in many instances may be water-immiseible. Emulsion sticks normally have a hydrophilic phase, commonly containing the antiperspirant active in solution, this phase forming an emulsion with a second, more hydrophobic, liquid phase. The continuous phase of the emulsion is structured. Solution sticks typically have the antiperspirant active dissolved in a structured liquid phase which is polar and may comprise a I polar organic solvent, which is often water-miscible, and the polar phase can contain water. There is substantial literature on structuring, of...cosmetic compositions, for example as represented by antiperspirant or deodorant compositions. WO 03/059307 PCT/EP02/14525 Conventionally, many sticks have been structured using naturally-occurring or synthetic waxy materials, in which term we include materials which resemble beeswax, in that they soften progressively with increase in temperature until they are fluid, generally by about 95°C. Examples of wax-structured sticks are described in an article in Cosmetics and Toiletries, 1990, Vol 105, P75478, in US patents 5169626 and 4725432 and in many other publications, in some of which such material s are called solidifying agents, More specifically, it has been common practice for sticks to be structured or solidified by incorporating fatty alcohol 15 of castor wax J alcohol tend t to human skin; clothing when into the composition, often accompanied by a smaller amount Sticks which are structured with fatty b leave visible white deposits on application moreover the deposits can also transfer onto it comes into contact .with the skin and the wearer can, for example, find white marks at the armhole of the sleeveless garment. Fatty alcohols are often regarded as coming within the general category of waxy materials, but we have observed that they are a more significant source of white deposits than various other waxy materials Some alternative structurants or solidifying agents to waxy-materials have been proposed. For example, the use of dibenzylidene sorbitol (DBS) or derivatives thereof as gellant for a polar or hydrophylic carrier liquid has been proposed in a number of publications such as EP-A-5-1-277-0-, 11 WO-92/19222, US!4954333, US 4822602 and US 4725430. Formulations containing such gellants can suffer from a number of disadvantages, including instability m the WO 03/059307 PCT/EP02/14525 presence oflacidic antiperspirants,.and comparatively high processing temperatures needed in the production of sticks. Other alternative proposed structurants include various classes of esters or amides that are solid at ambient temperature and are capable of solidifying a hydrophobic or water-immiscible liquid carrier. One such class comprises ester or amide derivatives of 12-hydroxystearic acid, as described in inter alia US-A-5750096. Another class of such esters or amides comprises N-acyl amino acid amides and esters, of which N-Lauroyl-L-glutamic acid di-n-butylamide is commercially available from Ajinomoto under their designation GP-1. They are described in US patent 3969087. A further class which has been disclosed as gelling agents comprises the amide derivatives of di and tribasic . carboxylic acids set forth in WO 98/27954 notably alkyl N,N'-dialkyl succinamides. Yet other amide structurants for water-immiscible liquid carriers are described in EP-A- 1305604. hough many amido-structurants have been identified already, it remains an objective to locate others which may meet the exacting standards of the cosmetic industry and ameliorate or eliminate one or more of the difficulties or disadvantages associated with the various amido structurants that have already been proposed or used. One further class of compounds which contain a -CO-NH- group 11' comprises cyclodipeptides, which are cyclic derivatives of aminoacids. Various cyclodipeptides has been described in an article by K Hanabusa et al entitled Cyclo(dipeptide)s as WO 03/059307 PCT/EP02/14525 low molecular-mass Gelling Agents to harden Organic Fluids, J. Chem Soc. Commun., 1994 ppl40l/2. The cyclodipeptides satisfied the general formula R2 in which Rx and R2 are designated organic residues. The selection exemplified included two materials (8 and 9) in which Ri represented alkyl esters, being either -CH2C02CH2CH2CH2Me or -CH2C02CH2CH2CHMeCH2CH2CH2CHMe2 and R2 represented -CH2Ph. This paper is herein referred to as Hanabusa I. In an introductory section, Hanabusa states that the most difficult problem for the development of low molecular mass gelling agents is how to stabilise the formed gel, in other words how to prevent the transformation from the metastable II qel to a crystalline state. Having conducted an extensive II research programme into gels formed using low molecular mass gellants, the Applicants are able to,confirm that the stabilisation of such gels often does indeed represent a be exacerbated other cosmetic serious and difficult problem, and indeed a problem that can in cosmetic compositions by the presence of ingredients. Hanabusa I subsequently makes a general assertion that the formed gels (sic. employing" the exemplified cyclodipeptides in the list of organic fluids given in Table 1) were stable even after several months. WO 03/059307 PCT/EP02/14?2? Various other cyclo(dipeptides) satisfying formula 1 above were described in a second article by Hanabusa et al entitled Low Molecular Weight Gelators for Organic Fluids: Gelation using a Family of Cyclo(dipeptide)s, in the Journal of Colloid and Interface Science 224, 231-244 (2000), hereiln called Hanabusa II. The text disclosed materials no 22 to 28, which were further esters like those of materials :8 and 9 in Hanabusa I, except that they were derived from different alkanols. Applicants have found that such esters, and in particular 27 and 28 in Hanabusa II, produced gels that were only poorly stable. Applicants tested a number of materials as gellants in oils that are common in cosmetic formulations in accordance with Formula 1 in Hanabusa I, 11-27 and 11-28, which seemed to be Hanabusa's best gellants. Unfortunately, the resultant products demonstrated inferior storage characteristics, at laboratory ambient temperatures-. Applicants deduced- that at best, the capability of cyclodipeptides to gel organic fluid stably could vary significantly, depending on the chemical nature of the substituent residues Ri and R2 • ii A number of cyclic dipeptide derivatives have been described as gellants in Japanese kokai No 2001-247451, in the name of Pola Chemical Industries Inc and Nisshin Oil Mills Ltd. These were either alkyl derivatives, which had already been described by Hanabusa or the unsubstituted cyclohexyl derivative which likewise showed inferior stability when I tested in the same manner as those proposed by Hanabusa. WO 03/059307 PCT/EP02/14525 SUMMARY OF THE INVENTION Applicants have now found that selected cyclodipeptide derivatives can be used as structurants for cosmetic compositions I When used as a modest percentage of the composition, typically not more than 15% by weight and often less than 10% by weight, they are able to structure the composition in a manner that is superior to that achieved by material 11-27 and 11-28 of Hanabusa. Indeed, at the same ! be recognised! alternatively time, and where appropriate, the composition can yield a deposit with [no worse than a low visible residue. It will that cyclodipeptide derivatives herein may be called diketopiperazine derivatives. It is an object of the present invention to provide structured cosmetic compositions, in which a liquid carrier material is ste ructured using a structuring agent which is different from those mentioned above. A further object" of" the invention is to provide a structurant which can exhibit a superior property to at least structurants 11-27 and 11-28 of Hanabusa identified above. A yet further object of some embodiments of the invention is to provide compositions which exhibit low visible deposits. It has been found that the properties of gels in hydrophobic carrier liquids can be improved by esterifying a cyclo(dipeptidej) acid with an alcohol producing a cyclic residue. WO 03/059307 PCT/EP02/14525 - 8 - Broadly, in La first aspect of the,present invention, there is provided a cosmetic composition comprising: (i) an antiperspirant active material 5 (ii) a continuous phase which comprises water-immiscible liquid carrier, and II (ii) a strucfcurant therein which comprises a cyclodipeptide derivative having the general formula O 10 in which RA represents a carbocyclic, or heterocyclic group containing not||more than 2 rings, other than unsubstituted cyclohexyl. Such cyclodipepjtide compounds are sometimes referred to 15 herein as DOPA derivatives or DOPAD and the residue containing the cyclodipeptide and the carboxyl group is ! sometimes called herein a DOPA residue. WO 03/059307 PCT/EP02/14525 For the avoidance of doubt, in the DOPA derivatives employed herein, the DOPA residue cyclic group within RA is directly bonded to the 10 A DOPA derivative as above serves as a structuring agent for the water^immiscible liquid carrier and when used in a sufficient amount, which is likely to be less than 15% of the total composition, is able to structure this liquid into a gel with sufficient rigidity to sustain its own shape. ii We have observed that the structuring compounds used in this invention form fibres or strands within the liquid phase. Without being bound to any specific theory or explanation, 15 we believe that upon gel formation a network of such fibres is formed which extends throughout the liquid phase. Upon heating the gel to the gel melting temperature, the strands of structurant dissolve and the liquid phase becomes more mobile. 20 25 In order to promote good sensory properties at the time of use it is preferred to include a silicone oil as at least a Ifraction of the water-immiscible carrier liquid. The amount of silicone oil may be at least 10%"by weight of the composition and/or at least 25% by weight of the water- immiscible carrier liquid. 30 Fatty alcohols which are solid at room temperature of 20°C, such as stearyjl alcohol, lead to deposits with an opaque white appearance and are preferably substantially absent, by which we mean present in an amount of no more than 3% by WO 03/059307 PCT/EP02/14525 weight of the composition, more preferably less than 1% and ji ! ' most preferably 0%. As already mentioned, fatty alcohols are often regarded as coming within the general category of. waxy materials. More generally the term "wax" is conventionally applied to a variety of materials and diversity in properties. mixtures (including some fatty alcohols) which have some (chemical structure but similarity in physical jThe term generally denotes materials which are solid at 30°GI, often also solid up to 40°C, having a waxy 10 appearance ori feel, but which gradually soften and eventually melt to a mobile liquid at a temperature below 95°C usually below 90°C. ii Possibly the composition does not include more than 3% of any material which is a wax, ie a solid at 3 0°C but softens II at an elevated temperature and at 95°C is molten and soluble l| in the water-immiscible liquid, yet which is unable to form a network of fjibres therein on cooling to 20°C. As^w-ill be explained in more detail below, in cosmetic compositions herein, the structured water-immiscible carrier liquid may be the continuous phase in the presence of a dispersed second phase, which may comprise a suspension of II particulate solid forming a suspension stick or a dispersion of droplets ofjja lypohobic liquid. Such a solid may be a particulate antiperspirant or deodorant active or pigment. II . aforementioned hydrophilic ie Such a disperse liquid phase may comprise a solution of the active or actives in water or other lypophobic solvent. WO 03/059307 PCT/EP02/14525 more stable, compositions Hanabusa. Further advantages of preferred structurant materials of this invention are that the gels they produce are physically both during processing and in the resultant by comparison with gellants 11-27 and 11-28 of f A composition of this invention will generally be marketed in a container by means of.which it can be applied at time II ' of use. This container may be of conventional type. A second aspect of the invention therefore provides a cosmetic product comprising a dispensing container having an aperture for delivery of. the contents of the container, means for urging the contents of the container through the said aperture i and a composition of the first aspect of the invention in the container. Means for urging the contents of the container to the said II aperture or apertures, for flow through them, may be moving parts operable by the user or an orifice in the container opposite the aperture providing digital access. The compositions of this invention can be produced by conventional processes for making cosmetic solids. Thus, according to a third aspect of the present invention there is provided a process for the production of a cosmetic composition comprising the steps of: • ai) incorporating into a water-immiscible liquid carrier a!structurant which is one or more structurant compounds las defined in the first aspect, WO 03/0*9307 PCT/EP02/14525 a2) mixing the liquid carrier with a solid or a disperse liquid phase comprising cosmetic active in particulate or dissolved form;to be suspended in the water-immiscible liquid, !' a3) heating the liquid carrier or a mixture containing it to ari elevated temperature at which the structurant is dissolved or dispersed in the water-immiscible liquid carrier, • steps al) a2) and a3) being conducted in any order followed by: • bl) introducing the mixture into a mould which preferably is a dispensing container, and then • cl) cooling or permitting the mixture to cool to a temperature at which the liquid carrier is solidified. A^suspended solid may be any cosmetic active that is at least partly insoluble in the lypophilic water-immiscible liquid carrier in the amount incorporated therein and a disperse liquid phase may be a solution of such an active in a hydrophilic or polar solvent. Lrfa fourth aspect of the present invention, the cosmetic active comprises an antiperspirant or deodorant active. According to the fourth aspect, there is provided a cosmetic method for preventing or reducing perspiration or odour formation on human skin comprising topically applying to the skin..a composition comprising an antiperspirant ..or....deodorant active, a waterl|immiscible liquid carrier and a structurant compound as defined above in the first aspect. WO 03/059307 PO7EP02/14525 13 - In a fifth aspect of the present invention there are provided novel ester derivatives of DOPA according to the general formula given in the first, aspect. In a sixth aspect of the present invention there is provided a process for making the novel esters of the fifth aspect in which DOPA acid is reacted with at1least an equimolar amount II of an alcohol of formula RAOH in the presence of at least 0.5 II moles of promoter per mole of DOPA acid in a reaction medium 0 comprising di methyl sulphoxide. DETAILED DESCRIPTION AND EMBODIMENTS As mentioned hereinabove, in accordance with the first aspect, the invention requires a structurant compound within a water-immiscible liquid phase. Other materials may also be present depending on the nature of the composition. The II various materials will now be discussed by turn and II ; preferred features and possibilities will be indicated. The structurant compounds of the present invention satisfy the general formula: WO 03/059307 PCT/EP02/14525 14 in which group contain! unsubstituted RA represents a carbocyclic or heterocyclic ng not more than 2 rings, other than cyclohexyl. Desirably, the substituted by carbocyclic or heterocyclic group in RA is at least one alkyl, ether or ester unsaturation. aromatic group substituent and/or contains at least! one degree of ring The ring unsaturation may result in a non-, for example comprising 1 or 2 degrees of unsaturation or an aromatic group. Although gels made using the derivative in which RA represents an unsubstituted cyclohexyl group are relatively unstable during storage under normal storage conditions, stability can be improved by distributing one or more substituents around the ll cyclohexyl group or by introducing unsaturation or a hetero atom. Herein, RA can comprise two fused rings, but preferably comprises a single six membered ring, either carbocyclic or WO 03/059307 PCT/EP02/14525 15 heterocyclic!, or a bridged ring. When A is carbocylic, it can be either saturated or unsaturated, preferably unsaturated or aromatic. When RA is heterocyclic, it is preferably saturated. Although the cyclic group within Rft can be unsubstituted, with the exception of cyclohexyl, it is preferably substituted by at least one alkyl substituent, which preferably contains no more that 16 carbon atoms. In some highly desirable embodiments the alkyl substituent has a longest chain length of up to 4 carbon atoms, and in certain or those a total carbon content of up to 5 carbon-atoms. II The alkyl substituent may be linear' or branched. Preferred examples include methyl, ethyl, propyl, isopropyl, butyl isobutyl or t-butyl or isopentyl. In a number of very suitable DOPA derivatives, RA contains two or more alkyl substituents and especially those selected from the above II list of preferred examples. The alkyl substituents may be the same, such a combination as two or more methyl substituents, or may be of different substituents such as a methyl and I isopropyl substituents. When RA is saturated, the substituents may depend from the same carbon atom in the ring, such as two methyl groups, or from different carbon atoms. In several highly desirable derivatives, two alkyl substituents are meta or para to each other, for example meta methyl groups or a para methyl and isopropyl group. In yet other derivatives, the ring may include a methylene bridge, which preferably likewise completes a six membered ring. WO 03/059307 PCT/EP02/14525 In some suitable DOPA derivatives, ' the or one alkyl li substituent may be ortho or para to the bond with the DOPA residue, as in 4-methyl-phenyl-. In some or other DOPA derivatives, the bond with the DOPA residue is-met a-to one- 5 or preferably two methyl substituents. When RA is heterocyclic, the heterocyclic atom is suitably nitrogen. Conveniently, the heterocyclic atom can be para to the bond with the DOPA residue. ; Moreover, in a number of desirable derivatives, the heteroatom is ortho to at least one alkyl group, better in a saturated ring and especially to up to 4 ortho methyl groups. The group RA is often most easily referred to as the residue II from the corresponding alcohol which may be reacted with RA include the phenol, and 2, DOPA to form the ester linkage. Thus, desirable examples of residues from 4-alkyl; phenol, such as 4-nonyl- 6-dialkyl- or 2,2, 6, 6-tetraalkyl*-4- piperidinol, such as 2 , 2,6,6-tetramethyl-4-piperidinol. In some especially preferred DOPA derivatives, the ring in Rfl is carbocyclicl and is substituted by at least two alkyl groups of which at least one is methyl and the other or one of the others is isopropyl. Examples of such RA residues include menthol, thymol, isopinocamphenol and 3,5-dialkyl cyclohexanol such as 3,5-dimethyl cyclohexanol. Especially desirably, the Lmethyl group is para to the isopropyl group as in the derivatives from carvacrol. The DOPAD from thymol i.s_paj£ticularlyj suitable, because of,.:i.t.s.jza.pability to.form hard, clear and! stable sticks. WO 03/059307 PCT/EP02/14525 17 Although many suitable DOPAD compounds described herein are substituted by an alkyl substituent or substituents, at least one of the substituents can itself be ethylinically unsaturated ie comprise an alkenyl!' group which in many instances contains from 2 to 6 carbons. Suitable examples I! include isopropenyl and isobutenyl. Such an unsaturated group may be employed instead of the corresponding saturated alkyl group containing the same number of carbon atoms as described hereinabove. One suitable DOPAD compound 10 comprises the derivative from carveol 15 In further compositions, the DOPAD compound may be substituted by an ether or ester, particular in respect of aromatic derivatives, such as benzoate esters. Such esters I : typically contain up to 10 carbons in the ester substituent Suitable DOPAD groups containing an ester substituent include ethyl benzoate, butyl benzoate, and hexyl benzoate. The DOPA derivatives used in this invention may be a mixture 20 of compounds within the general formulae given, or may be a single compound. These DOPA derivatives can be prepared by reacting the respective alcohol with DOPA in acid form (DOPAA), or 25 possibly with an acid chloride, or possibly an anhydride or an ester containing a DOPA residue. DOPAA can be obtained by li cyclising aspartame. The amount of the said DOPA derivatives in a composIt.ian .of 3 0 this invention is likely to be from 0.1 to 15% by weight of the whole composition and preferably from 0.1 up to 10%, and WO 03/059307 PCT/EP02/14525 18 - more commonly at least 0.3% and in many instances not'more than 5'- In some especially desirable embodiments, the amount of DQPA structurant is from 0.5% to 3.5* Herein, unless other wise stated, a % is by weight based on the entire composition. If the composition is an emulsion with a separate disperse phase, the amount of structurant compound(s) is likely to be from 0.15 to 20% by weight of the continuous phase, more likely from 0.4% to 8% of this phase. In some highly desirable embodiments the hydrophobic 10 carrier phase contains from 1.5 to'4.5% by weight based on that phase ofj the DOPAD. It will be recognised that the invention DOPA structurants are particularly advantageous because they are able to produce hard gels at even low concentrations of structurant. This is beneficial, not only II 15 because reduces the cost of the structurant, often a relatively expensive ingredient, but also releases formulation space for incorporating other desirable ingredients in the composition and reduces the amount of ingredient which might contribute to visible deposits. Use 20 of a smaller amount of structurant can also assist during II the preparation of gelled compositions, offering more flexibility to the step forming a carrier liquid with well dispersed or dissolved gellant. 25 Carrier liquid! 30 The water-immiscible carrier liquid comprises one or a mixture of materials which are relatively hydrophobic so as 11 to be immiscible in water. Some hyd'rophilic liquid ..may... be included in the carrier, provided the overall carrier liquid mixture is immiscible with water. It will generally be WO 03/059307 PCT/EP02/14525 19 desired that this carrier is liquid (in the absence of structurant) at temperatures of 15,°C and above. It may have some volatility but its vapour pressure will generally be less than 4kPa (30 mmHg) at 25°C so that the material can be. referred to as an oil or mixture of oils. More specificallyj it is desirable that at least 80% by weight of the hydrophobic carrier liquid should consist of materials with a vapour pressure not over this value of 4kPa at 25°C. 10 It is preferred that the hydrophobic carrier material includes a volatile liquid silicone, i.e. liquid polyorganosiloxane. To class as "volatile" such material should have a measurable vapour pressure at 20 or 25°C. Typically the vapour pressure of a volatile silicone lies in 15 a range from 1 or 10 Pa to 2 kPa at 25°C. 20 25 30 It is desirab'le to include volatile silicone because it gives a "drier" feel to the applied film after the composition is applied to skin. Volatile polyorganosiloxanes can be linear or cyclic or mixtures thereof. Preferred cyclic siloxanes include | polydimethylsiloxanes and particularly those containing from atoms and mos otherwise oft 3 to 9 silicon atoms and preferably hot more than 7 silicon by themselves centistokes), t preferably from 4 to 6 silicon atoms, en referred to as cyclomethicones. Preferred linear siloxanes include polydimethylsiloxanes containing from 3 to 9 silicon atoms. The volatile siloxanes normally exhibit viscosities of below 10"5 m2/sec (10 and particularly above 10"7 m2/sec (0.1 WO 03/059307 PCT/EP02/14525 - 20 centistokes) viscosity of volatile sii , the linear siloxanes normally exhibiting a below 5 x 10"6 m2/sec > (5 centistokes) . The icones can also comprise branched linear or cyclic siloxanes such as the aforementioned linear or cyclic |l siloxanes substituted by one or more pendant -0-Si(CH3)3 include oils and 246 from' groups. Examples of commercially available silicone oils having grade designations 344, 345, 244, 245 Dow Corning Corporation; Silicone 7207 and Silicone 7158 from Union Carbide Corporation; and SF1202 10 from General Electric, The hydrophobic carrier employed in compositions herein can alternatively or additionally comprise non-volatile silicone oils, which include polyalkyl siloxanes, polyalkylaryl 15 siloxanes and polyethersiloxane copolymers. These can suitably be selected from dimethicbne and dimethicone I copolyols. Commercially available non-volatile silicone oils include products available under the trademarks Dow Corning 556 and Dow Corning 200 series. Other non volatile silicone oils Incorporation having a high 20 silicone oils include that bearing the trademark DC704. of at least some non-volatile silicone oil refractive index such as of above 1.5, eg at least 10% by weight (preferably at least 25% to 100% and particularly from 40 to 80%) of the silicone oils is often 25 beneficial in some compositions, because this renders it easier to match the refractive index of the constituents of the composition and thereby easier to produce transparent or translucent formulations. 30 The water-immiscible liquid carrier may contain from 0% to 100% by weight of one or more liquid silicones. Preferably, WO 03/059307 PCT/EP02/14525 - 21 - there is sufficient liquid silicone to provide at least 10%, better at least 15%, by weight of;the whole composition. Silicon-free hydrophobic liquids can be used instead of, or more preferably in addition to liquid silicones. Silicon-free hydrophobic organic liquids which can be incorporated include liquid aliphatic hydrocarbons such as mineral oils or hydrogenated polyisobutene, often selected to exhibit a low viscositjy. Further examples o'f liquid hydrocarbons are polydecene and paraffins and isoparaffins of at least 10 carbon atoms Other suitable hydrophobic carriers comprise liquid aliphatic or aromatic esters. Suitable aliphatic esters 5 contain at least one long chain alkyl group, such as esters derived from Ci to C2o alkanols esterified with a CB to C22 These esters isopropyl pal' adipate. alkanoic acid or C6 to C3.0 alkanedioic. acid.. The. alkanol. and. acid moieties or mixtures thereof are preferably selected such that they each have a melting point of below 2 0°C. include isopropyl myristate, lauryl myristate, mitate, diisopropyl sebacate and diisopropyl Suitable liquid aromatic esters, preferably having a melting i! least a fracti advantageous, point of below 20°C, include fatty alkyl benzoates. Examples of such esters include suitable C8 to C18 alkyl benzoates or mixtures thereof, including in particular Ci2 to C15 alkyl benzoates eg those available under the trademark-Finsolv. Incorporation of such alkyl benzoate esters as at on of the hydrophobic carrier liquid can be because they can raise the average of WO 03/059307 PCT/EP02/14525 - 22 volatile-silicone-containing carriers, and thereby render easier to obtain translucent or transparent formulations. Further instances of suitable hydrophobic carriers comprise liquid aliphatic ethers derived from at least one fatty alcohol, such as myristyl ether derivatives e.g. PPG-3 myristyl ethe r or lower alkyl ethers of polygylcols such as an ether having named as PPG-14 butyl ether by the CTFA. 10 15 20 Aliphatic alcohols which are liquid at 2 0°C may be employed, and it is especially desirable to employ those which are water-immiscible. These include branched chain alcohols of at least 10 carbon atoms such as isostearyl alcohol and II octyl dodecanol. Such alcohols can' assist in the process of 70% or 80% of formulations, II forming a solution of the DOPA derivatives in a water-immiscible carrier liquid during the manufacture of structured gels. Such alcohols can, often constitute from at least 10% or 15% by weight of the water-immiscible liquid carrier mixture, in many desirable mixtures comprising up to the mixture. In a number of convenient jthe proportion of such aliphatic alcohols in said mixture is from 10 or 15% to 30% by weight and in some II :, Y y others, the proportion is greater than 3 0% by weight. 25 30 However, aliphatic alcohols which are solid at 20°C, II normally linear alcohols, such as stearyl alcohol are preferably absent or present in no more than 3% by weight of the whole composition, as indicated"hereinbefore; "since they lead to visible white deposits when a composition is topically applied to skin. WO 03/059307 PCT/EP02/14525 23 - Silicon-free liquids can constitute from 0-100% of the II ■ • water-immiscible liquid carrier, but it is preferred that constituents I up to 80% of silicone oil is present and that the amount of silicon-free preferably constitutes up to 50 or 60% or even water-immiscible carrier liquid and in many instances from 10 to 60% by weight, eg 15 to 3 0% or 30 to 60% by weight, of the carrier liquid. Liquid Disperse Phase in emulsions! II 10 If the composition is an emulsion in which the DOPA derivative acts as a structurant in the hydrophobic continuous phase, the emulsion will contain a more polar or |l lypophobic disperse phase. The disperse phase may be a 15 solution of an active ingredient. The hydrophilic disperse phase in an emulsion commonly comprises water as solvent and can comprise one or more water soluble or water miscible liquids in addition to or in 20 replacement of water. The proportion of water in an emulsion according to the present invention is often selected in the range of up to 60%,; and particularly from . 10% up to 40% or 50% of the whole formulation. 25 One class of water soluble or water-miscible liquids comprises short chain monohydric alcohols, e.g. Ci to C4 and especially ethanol or isopropanol, which can impart a deodorising capability to the formulation. Ethanol gives "a cooling effect on application to skin, because it is very 30 volatile. It is preferred that thel content of ethanol or any other monohydric alcohol with a: vapour pressure above WO 03/059307 PCT/EP02/14525 - 24 - : 1.3kPa (10 mmHq) is not over 15% better not over 8% by II weight of the composition. include ethyl glycol, hexyl A further class of hydrophilic liquids comprises diols or polyols preferably having a melting point of below 40°C, or which are water miscible. Example's of water-soluble or water-miscible liquids with at least one free hydroxy group ene glycol, 1,2-propylene glycol, 1,3-butylene .ene glycol, diethylene glycol, dipropylene 10 glycol, 2-ethoxyethanol, diethylene glycol monomethylether, triethyleneglycol monomethylether and sorbitol. Especially preferred are propylene glycol and glycerol. In an emulsion the disperse phase is likely to constitute 15 from 5 to 80 or 85% of the weight of the composition preferably from 5 to 50 or 65% more, preferably from 25 or 3'5% up to 5'0 or 65%, while the continuous phase with the structurant therein provides the balance from 15 or 35% up to 95% of the weight of the composition. Compositions with 20 high proportion of disperse phase, i.e. from 65 to 85% disperse phase, may be advantageous,;because they can give good hardness even though the concentration of structurant may be only a small percentage of the total composition. However, compositions with a lower proportion of disperse 25 phase can also be advantageous because they tend to offer a drier and warmer feel. II : An emulsion composition will generally include one or more emulsifyinq surfactants which may be anionic, cationic, II 30 zwitterionic and/or nonionic surfactants. The proportion of emulsifier in the composition is often selected in the range WO 03/059307 PCT/EP02/14525 - 25 up to 10% by up to 5% by amount from emulsifiers desirable to weight and in many instances from 0.1 or 0.25 weight of the composition. Most preferred is an 0.1 or 0.25 up to 3% by weight. Nonionic are frequently classified by HLB value. It is use an emulsifier or a mixture of emulsifiers with an overall HLB value in a range from 2 to 10 preferably from 3 to 8. 10 It may be convenient to use a combination of two or more I! emulsifiers which have different HLB values above and below the desired value. By employing the two emulsifiers together in appropriate ratio, it is readily feasible to attain a weighted average HLB value that promotes the formation of an emulsion. 15 Many suitable emulsifiers of high HLB are nonionic ester or ether emulsif especially a about 2 to 8 0 iers comprising a polyoxyalkylene moiety, jpolyoxyethylene moiety, often containing from , and especially 5 to 60 oxyethylene units, 20 I and/or contain a polyhydroxy compound such as glycerol or sorbitol or other alditol as hydrophilic moiety. The hydrophilic moiety can contain polyoxypropylene. The emulsifiers additionally contain a hydrophobic alkyl, alkenyl or aralkyl moiety, normally containing from about 8 25 to 50 carbons and particularly from 10 to 30 carbons. The hydrophobic moiety can be either linear or branched and is often saturated, though it can be unsaturated, and is optionally fluorinated. The hydrophobic moiety can- comprise tallow, lard, Such nonionic 30 a mixture of chain lengths, for example those deriving from palm oil, sunflower seed oil or soya bean oil. surfactants can also be derived from a WO 03/059307 PCT/EP02/14525 - 26 25, ceteth-1 ethoxylated polyhydroxy (compound such as glycerol or sorbitol or other alditols. Examples of emulsifiers include ceteareth-10 to 0-25, steareth-10-25 (i.e. Cx6 to C18 alcohols 'with 10 to 25 ethylene oxide residues) and PEG-15-25 stearate or distearate. Other suitable examples include Cio-O.U fatty acid mono, di or tri-glycerides. Further examples include Ci8-C22 fatty alcohol ethers of polyethylene oxides (8 to 12 EO) 10 Examples of emulsifiers, which typically have a low HLB value, often a value from 2 to 6 are fatty acid mono or possibly diesters of polyhydric alcohols such as glycerol, sorbitol, erythritol or trimethylolpropane. The fatty acyl moiety is often from Ci4 to C22 and is saturated in many 15 instances, including cetyl, stearyl, arachidyl and behenyl. Examples include monoglycerides of palmitic or stearic acid, sorbitol mono or diesters of myristic, palmitic or stearic acid, and trimethylolpropane monoesters of stearic acid. 2 0 A particularly desirable class of emulsifiers comprises dimethicone copolymers, namely polydxyalkylene modified I dimethylpolysiloxanes. The polyoxyalkylene group is often a polyoxyethylene (POE) or polyoxypropylene (POP) or a copolymer of POE and POP. The copolymers often terminate in 25 Ci to C12 alkyl groups 3 0 Emerest™, Lamef Span™, Tween™ Suitable emulsifiers and co-emulsifiers are widely available under many trade names and designations including Abil™, Arlacel™, BrijTf", Cremophor™,-Dehydrol™,- Dehymuls™, orm™, Pluronic™, Prisorine™, Quest PGPH™, SF1228, DC3225C and Q2-5200. WO 03/059307 PCT/EP02/14525 27 - Cosmetic Actlives The cosmetic actives employable herein can comprise antiperspiraht or deodorant actives or pigments. 5 Antiperspirant Actives . ji ": The composition preferably contains an antiperspirant active. Antiperspirant actives, are preferably incorporated in an amount of from 0.5-60%, particularly from 5 to 3 0% or 40% and especially from 5 or 10% to 30 or 35% of the weight I! 10 of the composition. Antiperspirant actives for use herein are often selected from astringent active salts, including in particular aluminium, zirconium and mixed aluminium/zirconium salts, and complexes zirconium and 15 including both inorganic salts, salts with organic anions Preferred astringent; salts include aluminium, aluminium/zirconium halides and halohydrate salts, such as chlorohydrates and activated aluminium chlorohydrates. 20 Aluminium halohydrates are usually defined by the general formula Al2 (OHi) xQy.wH20 in which Q represents chlorine, bromine or iodine, x is variable from 2 to 5 and x + y = 6 while wH20 represents a variable amoimt of hydration. EP-A-6739 (Uni specification 25 Especially effective aluminium halohydrate salts, known as activated aluminium chlorohydrates, 'are described in lever NV et al), the contents of which is incorporated herein by reference. Some II activated salts do not retain their enhanced activity -in the 30 presence of water but are useful in substantially anhydrous WO 03/059307 PCT/EP02/14525 28 formulations, i.e. formulations which do not contain a II distinct aqueous phase. the range of or positive, Zirconium actives can usually be represented by the empirical-general formula: ZrO (OH) 2n_nzB2. wH20 in which z is a variable in from 0.9 to 2.0 so that the value 2n-nz is zero n is the valency of B, and B is selected from the group consisting of chloride, other halide, sulphamate, sulphate and mixtures thereof. Possible hydration to a 10 variable extent is represented by wH20. Preferable is that B II represents chloride and the variable z lies in the range from I 1.5 to 1.87. Iln practice, such zirconium salts are usually not employed by themselves, but as a component of a combined aluminium andjzirconium-based antiperspirant. 15 The above aluminium and zirconium salts may have co- II ordinated andzor bound water in various quantities and/or may be present as polymeric species1, mixtures or complexes. In particular}! zirconium hydroxy salts often represent a 20 ' range of salts having various amounts of the hydroxy group. Zirconium aluminium chlorohydrate may be particularly preferred. Antiperspirant complexes based on the above-mentioned 25 astringent aluminium and/or zirconium salts can be employed. The complex often employs a compound with a carboxylate group, and advantageously this is an amino acid. Examples of suitable amino acids include dl-tryptophan, dl-j/3-phenylalanine, ..dl-valine ,..._jdi--methionine 30 and /3-alanine, and preferably glycine which has the formula CH2(NH2)COOH. WO 03/059307 PCT/EP02/14525 - 29 It is highly of aluminium together wit disclosed in those Al/Zr literature. desirable to employ complexes of a combination halohydrates and zirconium chlorohydrates a amino acids such as Iglycine, which are US-A-3792068 (Luedders et al). Certain of complexes are commonly called ZAG in the. ZAG actives generally contain aluminium, zirconium and chloride with an Al/Zr ratio in a range from II 2 to 10, especially 2 to 6, an Al/Cl ratio from 2.1 to 0.9 and a variable amount of glycine. Actives of this 1' 10 preferred type are available from Westwood, from Summit and from Reheis. 15 20 Other actives which may be utilised include astringent titanium salts, for example those described in GB 2299506A. hydration and in the solid The proportion of solid antiperspirant salt in a suspension composition normally includes the weight of any water of any complexing agent that may also be present 'active. However, when the active salt is incorporated in solution in a hydrophilic solvent such as a glycol, its weight commonly excludes any water present. If the composi tion is in the form of an emulsion the antiperspirant active will be dissolved in the disperse 25 phase. In thi provide from 3 s case, the antiperspirant active will often to 60% by weight of the disperse phase, 30 Alternatively, suspension in particularly from 10% or 2 0% up to 55% or 60% of that phase the composition may take the form of a which antiperspirant active in particulate form is suspended in the water-immiscible liquid carrier. Such a composition will probably not. have any separate WO 03/059307 PCT/EP02/14525 - 30 - 10 15 20 aqueous phase present and may conveniently be referred to as ]i ; "substantially anhydrous" although it should be understood that some wa 1 active or as immiscible 1 size of the range of 0.1 ter may be present bound to the antiperspirant a small amount of solute within the water-'iquid phase. In such compositions, the particle antiperspirant salts often falls within the I to 200 jxm with a mean particle size often from 3 to 20,um. Both larger and smaller mean particle sizes can also be contemplated such as from 20 to 50/um or 0.1 to 3jum. ii Deodorant Actives Ii Suitable deodorant actives can comprise deodorant effective II ' concentrations of antiperspirant metal salts, deoperfumes, and/or microbicides, including particularly bactericides, derivatives, (triclosan), such as chlorinated aromatics, including biguanide of which materials known as Igasan DP300™ Iricloban™, and Chlorhexidine warrant specific mention. A yet another class comprises biguanide salts such as are available under the trade mark Cosmosil™. Deodorant actives are commonly employed at a concentration of from 0.1 to 25% by weight. Optional ingredients Other optional ingredients include wash-off agents, often 1 25 present in an jamount of up to 10% w/w to assist in the removal of the formulation from skin or clothing. Such wash-off agents are typically nonionic surfactants such as esters or ethers containing a C8 to C22 alkyl moiety and a hydrophilic moiety which can comprise a pblyoxyalkylene 3 0 group (POE or POP) and/or a polyol WO 03/059307 PCT/EP02/14525 31 A further optional constituent of the formulation comprises further structurants which can be employed in the DO PA derivative. Herein, the DOPAD may be structurant, by which is meant that is employed the DOPAD is further struc one or more addition to the primary 5 at a concentration that is higher than that of the further structurant. However, in some advantageous embodiments, the further structurant may be present" in an amount- that is at least that of the DOPAD. In such advantageous embodiments, acting to moderate the properties of the 10 further structurant such that the properties using the combined structurant system are superior in at least one I! ■ desirable respect to using the further structurant alone. The amount of is often from such further structurants in the formulation i zero to not more than 15% of the formulation. 15 In some instances, the further structurant •is present in a II :: weight ratio to the DOPAD of from 10:1 to 1:10. 20 25 30 The further structurants employable herein can be non- II polymeric or polymeric. Solid linear fatty alcohol and/or a wax may be included but are not preferred. In anhydrous compositions notably antiperspirants which are suspension referred to as salts thereof, sticks, non-polymeric further structurants, sometimes gellants, can be selected from fatty acids or such as stearic acid or sodium stearate or 12-hydroxy ste'aric acid. Linear fatty acids are preferably not used in aqueous sticks, e.g. aqueous emulsion sticks because they can form insoluble precipitates with aluminium ions. Other suitable gellants can comprise dibenzylidene alditols, e.g. dibenzylidene sorbitol. Further suitable gellants can comprise selected N-acyl amino acid derivatives, including ester and amide derivatives, such as WO 03/059307 PCT/EP02/14525 - 32 N-lauroyl glutamic acid dibutylamide, which gellants can be contemplated}in conjunction with 12-hydroxy stearic acid or an ester or amide derivative thereof. Still further gellants include amide derivatives' of di or tribasic I! e.g. dodecyl strueturants carboxylic acids, such as alkyl N,N' dialkylsuccinamides, iN,N'-dibutylsuccinamide . When employing further comprising N-acyl amino acid derivatives, in some highly desirably formulations,their weight ratio to DOPAD is selected in the range of 1:1 to 6:1. 10 Polymeric strikcturants which can be employed can comprise organo polysiloxane elastomers such as reaction products of a vinyl terminated polysiloxane and a cross linking agent or alkyl or alkyl polyoxyalkylene-terminated poly (methyl 15 substituted) or poly (phenyl substituted) siloxanes. A number of polyamides have also been .disclosed as 1 structurant'S' f'pr hydrophobic liquids. Polymers containing both siloxane and hydrogen bonding groups, which might be used as secondary structurants, have: been disclosed in 20 WO 97/36572 and WO 99/06473. If an aqueous disperse phase is present, polyacrylamides, polyacrylates or polyalkylene oxides may be used to structure or thicken this aqueous phase. 25 It has also been found that invention formulations can include a dibenzylidene alditol, such as dibenzylidene sorbitol, as additional structurant, possibly in conjunction with an N-acyl amino acid derivative., Desirably;, the proportion of the alditol in the formulation is selected in 3 0 the range of from 0.1 to 0.5% by weight. In such formulations, the weight ratio of DOPAD to the alditol, eg WO 03/059307 PCT/EP02/14525 33 - ii of 3:1 to 10 as GP-1 is al dibenzylidene sorbitol, is often selected within the range 1. When an N-acyl amino acid derivative such so employed, then the .weight ratio of DOPAD to alditol is often selected in the range of from about 4:1 to 10:1 and the derivative to from about 5 weight ratio of GP-1 or other amino acid DOPAD is commonly selected in the range of 2 to 2:3. 10 15 20 25 It is highly desirable that any further structurant employed herein is itself fibre-forming, that is to say forms a II fibrous structure within the. hydrophobic phase. Most preferably the fibre-forming structurant is one in which the fibrous structure is not visible to the human eye. I! J of up to 5%; already menti derivatives, The compositions herein can incorporate one or more cosmetic adjuncts conventionally contemplatable for cosmetic solids or soft solids. Such cosmetic adjuncts can include skin feel improvers, such as talc or finely divided polyethylene, for example in an amount of up to about 10%; skin benefit agents such as allantoin or lipids/ for example in an amount colours; skin cooling,agents other than the Loned alcohols, such a menthol and menthol often in an amount of up to 2%, all of these percentages being by weight of the composition. A commonly employed adjunct is a perfume, which is normally present at a concentration of from 0 to 4% and in many formulations from 0.25 to |2% by weight of the composition. Product Form |j i 3 0 The sticks produced employing the DOPAD structurants can be either opaque^ or translucent or even transparent, depending WO 03/059307 PCT/EP02/14525 - 34 at least partly on the extent to which the refractive indices (RI) of the appropriate ingredients are matched. Translucent or transparent formulations are possible- in respect of th'e invention formulations because the DOPAD It ' . structurant forms a fibrous structure within the liquid hydrophobic carrier that is not seen by the human eye. By matched herein is meant that the difference between the refractive indices is less than 0.005 and preferably less than 0.0 02. In suspension sticks, to achieve at least translucency, it is necessary to match the RI of the suspended cosmetic active, eg the particulate antiperspirant salt, with the RI of the suspending; carrier oil mixture. This can be assisted by a suitable choice of oils, and in 1.46, such as particulates, One comprises particular mixtures containing those having an RI of above 15 1.46, such as from 1.46 to 1.56. In regard to suspended RI matching can be assisted by two factors. crushing or grinding the particulates so as to reduce substantially or ideally eliminate hollow spheres which have a different RI, and the second comprises 20 controlling the particle size during the manufacture process or in a subsequent classification process to produce a particle size distribution having no more than a minor fraction in the region of 1 to 10 uM. Matching can be further assisted by modifying the RI of the suspended 25 cosmetic active, such as an aluminium-containing antiperspirant active by post treating it with water (re¬hydration) or by retaining a comparatively high water content -during -the manu-f actur-e -process .- In emulsion formulations, the relevant ingredients to RI match comprise 3 0 the disperse and continuous liquid phases. WO 03/059307 PCT/EP02/14525 - 35 - It is highly desirable to employ RI. matching as indicated above in conjunction with the exclusion, to the extent necessary, of additional suspended materials having a different refractive index from the1 suspending medium, such as for example a' suspended filler or additional cosmetic active, to enable the resultant composition to transmit at II least 1% light (in the test described hereinafter) . II container has and means for Mechanical Properties and Product Packages The compositions of this invention are structured liquids and are firm in appearance. A composition of this invention will usually be marketed as a product comprising a container with a quantity of the composition therein, where the an aperture for the delivery of composition, urging the composition in the container towards the delivery aperture. Conventional containers take the form of a barrel of oval cross section with the delivery aperture at one end of the barrel 0 A composition of this invention may be sufficiently rigid that it is not apparently deformable by hand pressure and is suitable for use as a stick product' in which a quantity of the composition in the form of a stick is accommodated within a container barrel having an open end at which an end 5 portion of the stick of composition is exposed for use. The opposite end of the barrel is ofteh closed. Generally thejcontainer will include a cap for its open end and a component part which is sometimes referred to as an elevator or piston fitting within the barrel and capable of relative axiall movement along it. The stick of composition WO 03/059307 PCT/EP02/14525 36 - is accommodated in the barrel between the piston and the II open end of the barrel. The piston is used to urge the stick of composition along the barrjel. The piston and stick of composition may be moved axially along the barrel by finger or rod possibility i manual pressure on the underside of the piston using a inserted within the barrel. Another s that a rod attached to the piston projects through a slot or slots in the barrel and is used to move the piston and stick. Preferably the container also 10 includes a transport mechanism for moving the piston comprising a threaded rod which extends axially into the stick through a correspondingly threaded aperture in the piston, and means mounted on the barrel for rotating the II rod. Conveniently the rod is rotated by means of a hand- 15 wheel mounted on the barrel at its closed end, i.e. the opposite end to the delivery opening. 20 The component thermoplastic polyethylene. which include parts of such containers are often made from materials, for example polypropylene or Descriptions of suitable containers, some of further features, are, found in US patents 4865231, 5000356 and 5573341. 25 30 Composition Preparation I! Compositions of this invention can be produced by conventional processes for making cosmetic solids. Such processes invqlve forming a heated mixture of the composition at; a temperature which is sufficiently elevated I! that all the structurant dissolves, pouring that mixture into a mould, which may take the form of a dispensing WO 03/059307 PCT/EP02/14525 37 container, and] then cooling the mixture whereupon the structurant solidifies into a network of fibres extending II through the waiter-immiscible liquid phase. A convenient process sequence for a composition which is a suspension comprises first forming a solution of the structurant in the water-immiscible;liquid or one of the water-immiscible liquids. This is normally carried out by-agitating the mixture at a temperature sufficiently high that all the structurant dissolves (the dissolution temperature) such as a temperature in a range from 50 to 140°C. Thereafter, the particulate!constituent, for example particulate antiperspirant active, is blended with the hot mixture. This must be done slowly, or the particulate solid must be preheated, in order to avoid premature gelation. The resulting blend is then introduced into a dispensing container such as a stick barrel. This is usually carried out at a temperature 5 to 30°C above the setting temperature of the composition. The container and contents are then cooled to ambient temperature. Cooling may be brought about by nothing more than allowing the container and contents to cool. Cooling may be assisted by blowing ambient or even refrigerated air over the containers and their contents. suspension st conveniently aqueous or hy&rophilic disperse phase is prepared by In a suitable procedure for making emulsion formulations, a solution of the structurant in the water-immiscible liquid phase is prepared at an elevated temperature just as for icks. If any emulsifie.r is being used, this is I :j .mixed into this liquid-phase -Separately- an introduction of antiperspirant active into the liquid part WO 03/059307 PCT/EP02/14525 38 of that phase (if this is necessary": antiperspirant actives can sometime be supplied in aqueous; solution which can be utilised as i s) If possible, this1 solution of antiperspirant active which will become the disperse phase 5 is preferably heated to a temperature similar to that of the continuous phase with structurant therein, but without exceeding the boiling point of the solution, and then mixed 10 15 20 with the continuous phase. Alternatively, the solution is introduced at a rate which maintains the temperature of the mixture. If it is necessary to work at a temperature above the boiling temperature of the disperse phase, or at a temperature where evaporation from this phase is II '! significant, a pressurised apparatus could be used to allow a higher temperature to be reached. With the structurant materials of this invention this isi usually unnecessary. After the two phases are mixed, the resulting mixture is filled into dispensing containers, typically at a temperature 5 to 3 0°C above the setting temperature of the composition, and allowed to cool as, described above for suspension sticks. Many of the cpsmetic composition according to the present invention employ a mixture of hydrophobic carrier fluids. In some convenient preparative routes, it is desirable to II 2 5 dissolve the DOPAD structurant in a liquid component of the composition, such as an alcohol, eg an alcoholic carrier fluid, ie, a branched aliphatic alcohol, eg isostearyl alcohol or octyldodecanol, optionally in conjunction with an alcohol having some water-miscibility and boiling point" 3 0 above the dissolution temperature of DOPAD in the alcoholic fluid. This enables the remainder of the carrier fluids to WO 03/059307 PCT/EP02/14525 39 avoid being taken to the temperature at which the DOPA dissolves or melts. The proportion! of the carrier fluids for dissolving the DOPA is often from 15 to 65% by weight of I! the carrier fluids, and particularly from 20 to 40%. Structurant Preparation i; The DOPA derivatives employed as structurants herein can be made by esterdfying DOPA in acid form with the alcohol corresponding to the residue desired in the DOPA derivative. of a substant alcohol, such period. Desi In one convenient precursor step, the DOPA acid (DOPAA) can be made by cyclising aspartame, preferably in the presence ial excess of a low molecular weight aliphatic reaction, the the resultant as isopropanol, under reflux for a long rably, the alcohol is employed in. a weight ratio to aspartame of greater than 50:1 such as up to 100:1, and the reaction is continued for at least 10 hours at reflux temperature, such as from 15 to 24 hours. During the aspartame gradually dissolves. On cooling, solution yields a white powder. Removal of the solvent from the filtrate yields a solid which, after washing with acetone, provides a further amount of the white product, confirmed by a combined yield of the DOPA acid of 79 %. DOPAA can be[reacted with the relevant alcohol of formula RAOH, preferably in a mole ratio to; the DOPAA of at least 1:1 to 10:1, particularly from 1.5:1 to 7:1 and especially at least 2.-1 in 'dimethyl sulphoxide,..conveniently in a ratio of at least 4 :1 I; (vol :wt) , preferably from 6:1 to 12:1, and preferably in; the presence of a promoter, such as a WO 03/059307 PCT/EP02/14525 - 40 - carbonyldiimidazole, in an amount preferably from 0.5 to 2 moles of promoter per mole of DOPA acid. The reaction is conveniently carried out at a mildly elevated temperature, such as up to 60°C and particularly^ from 40 to 60°C for a 5 period of at least 6 hours and preferably from 9 to 24 hours. The resultant solution is quenched in excess ambient or cooler water, desirably after the solution has cooled to ambient, a solid precipitates and is filtered off, water washed until no residual diimidazole remained and then can 10 be purified by washing with diethyl, ether or toluene, and 11 dried. WO 03/059307 PCT/EP02/14525 41 - EXAMPLES Example 1 and 1Comparisons CA to CI ' |l Preparation of Strueturants ii These Examples and Comparisons werei carried out by the following general method employing (2S-cis)-(-)-5-benzyl-3,6-dioxo-2-piperazine acetic acid (DOPAA) which was reacted with the alcohols and the amounts of reagents and promoter specified in Table 1 below. 10 A 250 ml 3 necked round bottomed flask equipped with a I! i. stirrer was charged with (2S-cis) - (,-) -5-benzyl-3 , 6-dioxo-2- piperazine acetic acid (DOPAA), and;> methyl sulfoxide (8mls per lg of DOPAA) was then introduced at laboratory ambient 15 temperature (about 22°C) with stirring. The DOPAA dissolved only partially. 1,1'-carbonyldiimidazole was then II introduced with stirring in the amount specified in the Table. Vigorous effervescence occurred and the reaction mixture was left stirring at room temperature for 45 minutes 20 after which time the reaction mixture went clear. The specified alcohol was stirred into the clear reaction mixture and maintained at 50°C overnight (between 16 and 2 0 hours), whereupon it was allowed to cool to ambient temperature (about 22°C), and poured into water, producing a 25 ' precipitate which was filtered off and washed with further quantities off water until any residual diimidazole had been removed (as shown by 1Hnmr) . The washed precipitate was then washed with diethyl ether, except for CB which was washed with toluene.; The washed product was'dried in a vacuum oven 30 to constant weight and its melting point determined, the results quoted herein being obtained by DSC with a heating WO 03/059307 PCT/EP02/14525 42 rate of 10 C/min, except for those marked , which were obtained using a an Electrothermal 9109 digital melting point measuri rig apparatus. The purity of certain of the products could be determined by the selected HPLC method, because such derivatives were not elutable. The DOPAD mat on a smaller the DOPAA was in 125ml DMSO by volume to erials in Examples 1.1.6 to 1.18 were produced scale using a modified reaction method in which activated with CDI in a single reaction vessel solution. Once activated, this was transferred 'a reaction tube in a Radleys'™ 12 place reaction carousel containing the appropriate amount of the chosen alcohol. 5 The purity of was measured (UV)detection DOPAD materials Exl. 1. to Ex 1.19 and CA to CK '.by reverse phase HPLC with ultraviolet O.OOlg of CDP made up to vo A mobile phase was made comprising 3 00ml aliquot of deionised water, to which was added a 700ml aliquot of HPLC grade acetonitrile and 1.0ml of trifluoroacetic acid (Aldrich spectrophotometric grade, TFA) and mixed thoroughly. sample was weighed into a 2 ml HPLC vial and .ume with the mobile phase. The sample was then analysed in a Hewlett Packard HPLC analyser equipped with a Hypersil ODS™ 5p.m Ci8, 250 x 4.6mm @ Room Temp column, a Hewlett-Packard 1050 Series Autosampler and Hewlett-Packard 1050 UV Diode Array• @--21Onm Ij Detector. The analysis was carried under the following conditions:- WO 03/059307 PCT/EP02/14525 - 43 - Isocratic/gradient 3 i; Flow rate Run time Temperature I! 5 Injection volume Isocratic 1.2ml/minute 5 minutes Ambient 2 0ul Table 1 Ex or Comp Alcohol I CDI DOPA Yield Purity MP 1 I mmol mmol mmol g % % °C 1.1 (1S,2R,£ Menthol ;s)-(+) 18 4.0 3.68 0.75 49 98. 7 238 1.2 Thymol i 73.6 16.2 14.7 3.3 56 99.3 212 1.3 Menthol (racemit 1 :> 73.6 16.2 '14.7 1.0 17 48.4 216 1.4 3,5-dimethyl- cyclohexanol * II 92 22 18.4 l; 1.5 21 94 212 1.5 2/2/6,6 jT tetramethyl- 4 - piperidinol F II 92 22 1 18.4 1.2 16 97.8 225 1.6 1R,2R,3R,5S- (-)-iS0r i pinocamphenol II 92 22 18.4 4.16 55 68 >200 1.7 Nonylph'e snol 92 22 18.4 4.07 46 83 .6 191 1.8 (1R,2S,E (-)-Ment JS)-.hol 92 22 18.4 7.72 51 85.9 233 1.9 4-t-butiyl phenol Ii 95.3 22.9 19.1 7.13 94 .6 99.1 237 1...1.Q 4-t-amyl phenol Ii 95.3 22.9 19.1 6.86 87.9 100 211 1.11 4-isoprppyl- phenol : Ii | 66.3 26.5 22.9 7.31 83.8 99.4 >230 WO 03/059307 PCT/EP02/14525 - 44 - WO 03/059307 PCT/EP02/]4525 45 Materials The materials used in gel studies or the preparation of cosmetic formulations, and their proprietary names, other than the products of Example 1, were as follows: 1) Isostearyfl. alcohol (ISA) (Pricer'ine 3515 ™ - Uniqema) 2) C12-i5 alky! benzoate (Finsolv TN ™ from Finetex Inc) 3) Octyl dodecanol (Eutanol G ™ - Cognis) 4) Volatile cyclomethicone (DC 245 ™ - Dow Corning Inc) 5) Hydogenatad Polydecene (Silkflo 3 64 NF ™- Albemarle) 6) 1,1,5,5-tetraphenyl trisiloxane (DC7 04™: Dow Corning Inc) 7) N-lauroyl Ajinomoto L-glutamic acid Di-n-butylamide (GP-1™-Co Inc) 8) Dimethicone Copolyol (Abil EM90™ -Th. Goldschmidt AG) 9) Al/Zr Tet'rachlorohydrex glycine, complex (Reach 908™ -Reheis Inc) 10) Milled Macrospherical AACH (A418™ - Summit) 11) 50% aqueous solution of Al/Zr pentachlorohydrate (Zirconal 50™ - BK Giulini) 12) Water-modified AZAG, made in house by freeze drying a solution particula particles 13) PG5 - Al/ Giulini) of AZAG (Rezal 67™) and sieving to obtain te solid free from hollow particles (-37% of 14) BMA - Benzyl alcohol - Acros 15) DBS - Dibenzylidene sorbitol (R'oquette Corp) 16) 12-HSA - 12-hydroxystearic acid (CasChem Inc) WO 03/059307 PCT/EP02/14525 - 46 17) Rezal 36 10 3P (solid Al/Zr tetrah'ydrochlorex glycine salt from Rehe 18) Reach 908 from Rehe 19) Versamid is Inc) (solid Al/Zr tetrahydrochlorex glycine salt is Inc) ' 93 0 - polyamide from Cbgnis 20) DDK H18, Silica from Wacker-Chemie GmbH 21) HDD H30, silica from Wacker-Chemie GmbH 22) HDD H30Rxi silica from Wacker-Chemie GmbH 23) tri (1,2-propanediol) n-butyl ether (Dowanol TPnB™ from Dow Corning Inc 24) propane-1 2-diol from Fisher 15 25) di (propane-1,2-diol) from Acros 26) PEG-3 0 dipolyhydroxystearate (Arlacel P13 5™ from Uniqema ii Example 2 - Structured Gels II !, In this Example, gels were made or attempted to be made in a number of representative organic solvents, having the refractive index shown in Table 2 below, using the structurants produced in Example 1 or the comparisons. 20 25 The gels were prepared in 3 0ml clear glass bottles. The solvent and gelling agent were weighed directly into the bottle to give a total mixture weight of lOg. A small Teflon stirrer bar was placed in the bottle and the mixture stirred and heated until the cyclo dipeptide had dissolved. The bottle was then removed from the heat and the solution allowed to cool and gel under quiescent conditions. The gel hardness was determined by a skilled assessor of 30 gels using a qualitative assessment' by comparison with standard gels after the gels had been stored at ambient WO 03/059307 PCT/EP02/14525 47 - temperature for 1 day or 3 days if over a week-end. The clarity was determined by visual assessment by comparison with standards and for some samples, light transmission measurements were made by the general method described in WO 00/61082, incorporated herein by reference. The results are summarised herein in Table 4. Gel stability was assessed of a number of samples employing the structurant at a concentration of 1.5% by weight by ii storing them for a long period at ambient temperature (20 to 25°C) and observing the change, if any in their appearance or properties after the stated length of time, which time month. The results are summarised in Table 5. Table 2 Solvent RI ISA- 1.455.9 Finsolv TN 1.4841 Eutanol G 1.4538 50:50 ISA: DC245 1.4278 50:50 ISA: Finsolv TN 1.4700 50:50 ISA ':' Silkflo 364NF II 1.4552 50:50 ISA:i)C704 1! 1.5059 WO 03/059307 PCT/EP02/14525 48 - Table 3 Transparency Hardness of gel :Descriptor 0 Opaque 0 Very soft G Gel t Translucent li 1 Soft ;;U Undissolved Solids T Transpare: it 2 Soft/Medium ■P Paste * % light transmits 5d 3 Medium L Liquids present 4 Medium/Hard D Did not dissolve 5 Hard nd not determined r Rubbery ■ Table 4 , Product of Ex 1.1 ! CA Ex 1.2 Liquid Carri er wt% Result wt% Result wt% Result ISA 1.5 2.5 5.0 t,3,G t,5,G t,5,G 1.5 2.5; 1' T,3,G t,5,G 1.5 T,5,G Finsolv TN 2.5 T,3,G 2.5' t,5,G Eutanol G 2.5 t,3,G 2.5" t,3;G 50:50 ISA: DC245 1.0 1.5 t,2,G t,3,G 1.0: 1.5, t,2,G t,3,G 1.5 T,5,G 50:50 ISA: Finsolv TN 1.5 2.5 T*93,3,G t,5,G 1.5 2.5'. t,3,G t,5,G 1.5 T*83,5,G 50:50 ISA : Silkflo 364N ? 1.5 t,4,G 1.5 t,3,G 1.5 T*81,5,G 50:50 ISA:DC704 | 1.5 T*91,5,G 1.5 T,5,G WO 03/059307 PCT/EP02/14525 - 49 - i; Product of Ex 1.3 Ex 1.4 Ex 1.5 Liquid Carri er wt% Result wt% ' Result wt% Result ISA 1.5 t,l,G 1-5! T,3,G 1.5 T,r,G+U 50:50 ISA: DC245 1.5 t,1,G+U 1.5; T,3,G+U 1.5 T,r,G+U 50:50 ISA: Finsolv TN 1.5 t,l,G+U 1.5i T*84,3,G 1.5 T,r,G+U 50:50 ISA : Silkflo 364t« F 1.5 t,1,G+U 1.5; T,3,G 1.5 T,r,G+U Product of Ex 1.6 • Ex 1.7 Ex 1.8 Liquid Carri er wt% Result wt% Result s vt% Result ISA 1.5 T,3,G 1.5 T,3,G 1.5 T,3,G 50:50 ISA: DC245 1.5 t;2,G+U 1.5, 0,3,G 1.5 U+L 50:50 ISA: Finsolv TN 1.5 T*68,3,G 1.5 t/0,3,G 1.5 T,3,G 50:50 ISA : Silkflo 364K F 1.5 t,l,G 1.5; 1 0,3,G 1.5 t,3,G ' Product of Ex 1.9 Ex 1.10 Ex 1.11 Liquid Carri er wt% Result wt%' Result wt% Result ISA 1.5 T,3,G 1.5 t,3,G 1.5 T,3,G 50:50 ISA: DC704 1.5 t,3,G 1.5;' T,3,G 25:75 ISA: DC704 i . j 1.5 T,3,G 1.5 T,3,G WO 03/059JO 7 PCT/EP02/14525 - 50 Product of Ex 1.12 Ex 1.13 Ex 1.14 Liquid Carrd er wt% Result wt%, Result wt% Result ISA 1.5 T,3,G 1.5. t,3,G 1.5 T,5,G 25:75 ISA: DC704 1.5. t,3,G 1.5 T,4,G 50:50 ISA: Finsolv TN 1.5 t,3,G Product of Ex 1.15 Ex 1.16 Ex 1.17 Liquid Carrj er wt% Result wt£ Result wt% Result ISA 1.5 t,3,G 1.5.: .i t,3,G 1.5 T,3,G 25:75 ISA: DC704 T,4,G 1.5 T,3,G 50:50 ISA: Finsolv TN t,3,G Product of Ex 1.18 Liquid Carrd er wt% Result ISA 1.5 t,3,G 25:75 ISA: DC704 1.5 T,2,G 50:50 ISA: Finsolv TN 1.5 T,3,G '■ \ WO 03/059307 PCT/EP02/14525 Product of | CB CC CD Liquid Carrier wt% Result wt% ': Result wt% Result ISA | 1.5 t,2,G 1.5' 0,0r,G 1.5 0,P 50:50 ISA: DC245 ! i 1.5 t,3,G 1.5: T,1,G (leaky) 1.5 U+L 50:50 ISA: Finsolv TN i 1.5 t,l,G 1.5 T,lr,G 1.5 0,P 50:50 ISA : Silkflo 3641s i 1.5 t,2,G 1.5,, T,lr,G 1.5 0,P Product of CE CF CG Liquid Carri er wt% ' Result wt% Result wt% Result ISA 1.5 U+L 1.5' 0,P 1.5 0,P 50:50 ISA: DC245 1.5 U+L 1.5| U+S 1.5 0,P •5-0-:-5-0 ISA: Finsolv TN 1.5 U+L .1..5L 0.,P. 1.5. Q,P 50:50 ISA : Silkflo 3641 IF 1.5 U+L 1.5 U+S 1.5 0,P Product of CI ' CJ CK Liquid Carri er wt% Result wt% Result wt% Result ISA 1.5 L+0,P 1.5 0,P 1.5 0,P 50:50 ISA: DC704 1.5 0,0,g 1.5 0,P 1.5 0,P 5 It will be recognised from the foregoing that.the comparison gelators, a number of which have been praised in the prior i art, are manifestly inferior to the gelators employed in the instant invention. WO 03/059307 PCT/EP02/14525 52 Table 5 Product of Ex 1.1 Ini tial Gel Description transparent, medium gels Gel Description after Storage at Room Temperature unchanged after 12 months Ex 1.2 Ex 1.3 transparent, hard gels I transparent, soft unchanged after 12 months unchanged after 12 months gel sol Ex 1.4 Ex 1.5 s + undissolved id transparent, medium gels transparent, soft, rubbery gels + undissolved solid unchanged after 12 months DC245- / Finsolv mixture initially started to turn opaque and leak solvent after 1 day, but did not deteriorate after 8 months. Ex 1.6 Ex 1.7 tra'hs lucent, II sofjt/medium gels transparent/opaque medium gels unchanged after 12 months slight loss of clarity after 3 months, but no further change in next 9 months. Ex 1.8 transparent medium unchanged after 8 months) gel s. No gel with DC2J45 mixture, Exl.9 transparent medium gels unchanged after 6 months WO 03/059307 PCT/EP02/14525 - 53 - ii Ex 1.10 transparent/transl ucent medium qels unchanged after 6 months Ex 1.11 transparent medium gel 1 unchanged after 6 months Ex 1.12 transparent hard gel 1 unchanged after 6 months Ex 1.13 tra'nslucent medium gels l( unchanged after 6 months Ex 1.14 transparent medium/hard gels II unchanged after 3 months Ex 1.15 tra 1 .ge] a 1 .nslucent medium s unchanged after 3 months Ex 1.16 translucent medium | unchanged after 2 months (will update) Ex 1.17 transparent medium gel II unchanged after 2 months (will update) Ex 1.18 transparent medium gel unchanged after 1 month (will update) Ex 1.19 tri or .nsparent medium medium hard gel unchanged after at least 7 months II WO 03/059307 PCT/EP02/14525 54 Product 1! Initial Gel Gel Description after Storage of Description IS * at Room Temperature CA transparent/ gels were unsuitable to make translucent, soft II sticks because they became / medium gels very soft and opaque within 2 weeks and leaky within 4 to 6 weeks CB translucent, gels were unsuitable to make so: t/medium gels sticks because they became very soft and opaque within 2 weeks and leaky within 4 to 6 weeks CC translucent, soft, gels were unsuitable to make rui bery gels sticks because they became opaque and collapsed within 1 day CD opa'que pastes or not a gel 1 whj te precipitates in clear solution : CE no gels not a gel CF die not dissolve not a gel or opi precipitated as ique crystalline slush li CG opa'que pastes not a gel CH tre inslucent medium gel became opaque, often or medium/soft gel i within days and collapsed .. . within 1 to 6 weeks I: WO 03/059307 PCT/EP02/14525 55 From Table 4, it can be seen than the invention structurants were able to produce gels in a wide range of representative hydrophobic liquid carrier systems, whereas various related structurants in RA did not satisfy the criteria of the I 5 ' instant invention were not so able. Some comparative (I structurants produced opaque pastes or simply produced a If , . „ , • . mixture of undissolved solids plus supernatant liquid. From Table 5, it can be seen that even those structurants 10 which produced gels initially, such;as CA, CB and CC, exhibited poor stability, becoming opaque and soft, followed by leaking, and/or collapsed quickly, whereas those gels produced using structurants according to the present invention were considerably more stable. Many of the II 15 invention gels were not showing any discernible change after several months. It will further more be recognised that the invention gellants employing RA that is unsaturated in the ring or a ring that is substituted by an alkyl ether or ester group is superior to a comparison DOPAD in which RA 20 represents cyclohexyl. Likewise, it can be seen that the invention DOPADs in which the ring is a direct substituent of the cyclic dipeptide are superior to comparisons in which an unsaturated (phenyl) ring is separated from the cyclic dipeptide by an intervening methylene group. 25 Examples 3 toll 6 - Cosmetic Stick Formulations A number of cosmetic stick compositions were prepared, containing the ingredients specif led-in-T-abies-S and•• 8 to 10 below. Their?' properties were measured by the "methods 3 0 described hereinafter and at the times indicated in the i; summaries. WO 03/059307 PCT/EP02/14525 - 56 - Example 3 - Opaque Suspension Sticks In Example 3, specified eye opaque sticks were made by dissolving the o dipeptide structuraht in the liquid alcohol or alcohol mixture, eg isostearyl alcohol whilst with heated and stirring using an overhead paddle stirrer until complete dissolution had occurred. In formulations additionally I! approximately desired solid and with gentl containing a further structurant, namely GP1 DBS and/or 12-HSA, the latter was dissolved into solution of the cyclo dipeptide structurant at a temperature of about 5 to 10°C lower. The remaining carrier oils were heated to 50°C and stirred using a stirrer bar and the antiperspirant active;was introduced slowly e stirring into them.: When all the active had been added, the mixture was sheared using a Silverson mixer II at 7000rpm for 5 minutes to ensure the active was fully dispersed. The active/oil mixture was then heated in an II oven to 85°C and mixed into the structurant solution which had been allowed to cool to 90°C. The temperature of the stirred mixture was kept at 85°C until it was poured into conventional commercial 50g stick barrels and allowed to cool except for formulations containing GP1 which were II poured at approximately 75°C. The formulations and properties of the sticks are summarised II 5 in Table 6 below. WO 03/059307 PCT/EP02/14525 - 57 - Table 6 Example No Ex 3.1 Ex 3.2 Ex 3 .3 Ex 3.4 Ex 3.5 Ingredient % by weight Ex 1.2 Product 1! 2.5 2.5 1.5 1 Ex 1.6 Produ fct ■ 1.5 GPl 2.5 3.0 2.5 Prisorine 35 15 35.75 35.75 30 28.2 30 Finsolv TN 35.75 20.9 DC704 35.75 40 40 DC245 20.9 Reach 908 26.0 26.0 26.0 26.0 26.0 J Properties Hardness (mm') 16.5 15.2 13.8 18.6 14.3 pay-off (g)a t0 on WetorC t ry 0.35 0.25 0.31 0.27 0.3 whiteness t=24hr on WetorDry 13 16 14 27 20 pay-off (g)a t0 on wool t 0.99 0.63 !0.82 0.63 1.08 whiteness t=24hr on wo 1! ol 17 17 16 15 20 II Comparative data for a commercial suspension stick 5 structured using GPl (GS) and a commercial wax-structured suspension stick (WS)is given in Table 7 below. WO 03/059307 PCT/EP02/14525 - 58 Table 7 Comparison GS WS Hardness (mm) pay-off (g) at tc on WetorDryj whiteness t;=24hr on WetorDry at t, pay-off (g) on wool whiteness t|=24hr on wool 11.3 0.40 28 0.61 23 10.3 0.39 121 1.10 110 From Table 7, it can be seen that sticks of acceptable firmness can be obtained using the invention structurants at 5 comparatively low concentrations of the structurant. measured by a and therefore Moreover, even though suspension sticks that are structured using the invention structurants are a- little- softer (as- penetrometer) than either the GS or WS sticks might be expected to suffer from a higher pay- off and higher visible deposits, the pay-off is similar to such sticks and the whiteness is, on balance, lower. Example 4 - Transparent Suspension Sticks The sticks in this Example were made using the process of Example 3 together with a preparatory step. In the preparatory st!ep, the RI of the antiperspirant active was first measured using a standard procedure (Becke. line-test)-The proportions of each of the carrier oils were then determined (through calculation and measurement) such that their weight averaged refractive index was closely matched WO 03/059307 PCT7EP02/14525 - 59 - to that of the active. The formulations are summarised in ll Table 8 below. Table 8 ' I! Example No 4.1 4.2 4.3 4.4 ' 4.5 4.6 4.7 4comp Ingredient % by weight Ex 1.2 1.51 1.5 1.5 1.0 Ex 1.4 0.70 Ex 1.7 1.5 Ex 1.1 1.0 GP-1 3.0 4.0 4.05 3.5 4.0 3.0 5.0 ISA 18.34 17.61 17.36 17.55 17.61 17.36 16.71 17.49 DC704 55.03 52.89 52.14 52.7 52.89 52.14 54.29 52.51 A418 25.12 25.0 25.0 25.0 25.0 25.0 25.0 A.2AG H2 25.0 Properties , Hardness (mm) | 23 14.7 13 .1 16.1 14.8 n/d 16.2 15.9 Clarity (%T) 44 12.7 15.4 12 .0 9.9 1.6% 0.7 5.9 Visual Score 8 2 1 3 , 0 pay-off (g)at i on wool 0 nd 0.88 0.54 0.92 0.58 n/d 0.83 0.97 whiteness t=24hr on wool nd 15 17 20 I 17 n/d 17 13 WO 03/059307 PCT/EP02/14525 Table 8 (cont) Example No 4.8 4.9 4.10 4.11 4.12 4.13 Ingredients % by weight Exl.2 2.81 1.5 1.7 1.5 1.5 Exl.9 3.0 GP-1 2.0 4.0 DBS 0.25 0.4 12-HSA 5.0 ISA I 8.81 17.8 18.46 15.51 15.735 DC704 42.36 29.47 53.45 52.48 52.99 53.765 Benzyl Alcohc 1 8.81 19.68 1.96 Finsolv TN 12.21 22.83 A418 25.0 25.0 25.0 25.0 25.0 P5G 25.0 Properties Hardness (mm) 14.0 20.1 13.5 17'.2 13.3 12.1 Clarity (% T) 23 .0 6.1 19.4 15.3 12.2 2.2 Clarity (visual score 1 ) n/d n/d 2 ■ 3 0 -9" WO 03/059307 PCT/EP02/14525 - 61 - I Tabl e 8 (cont) Example No 4.14 4.15 4.16 4 .17 4.18 Ingredients % by weight Exl.2 V i 1.7 2.0 Exl.14 1.0 Exl.15 0,7 Exl.16 [ " 0.4 GP-1 1 2.0 2.0 4.0 4.0 4.0 ISA 1 16.14 17.98 15.848 15.916 15.32 DC704 55.16 51.1 54.152 54.3 84 53.30 Benzyl Alcoho 1 1 1 1.92 1.98 A418 25.0 25.0 25.0 25.0 P5G 25.0 Properties Hardness (mm)' 14.4 14.2 13.7 14.2 16.9 Clarity (% TJ 13.2 26.6 27.5 15.0 8.7 Clarity (visual score1 ) 7 6 4 1 0 nd indicates Jthe property was not determined. From Table 8, it can be seen that a comparatively soft stick was obtainable using an extremely low concentration of structurant according to the present invention, a stick having excel1 ent clarity. Sticks containing GP-1 as co- structurant were harder, and still retained acceptable 10 clarity. Sti cks with similar hardness were obtainable with the incorporation of dibenzylidene sorbitol WO 03/059307 PCT/EP02/14525 - 62 Example 5 - Opjaque Emulsion Sticks In a first step in making opaque emulsion sticks according the present invention, a solution of the selected invention structurant, and if present GP1, in:ISA was made by the same li -'i (Example 3) . together with method as in the process for making,suspension sticks The remaining water immiscible carrier oils an emulsifier, Abil EM 90, were heated to 85°C in an oil bath whilst being shear mixed at 2500 rpm. The solution of antiperspirant active was heated to 8 0°C and 0 introduced gradually into the oil/emulsifier mixture, and the resultant mixture was kept constant by heating at 85°C and sheared at 7500 rpm for 5 minutes. The emulsion was the mixed into the solution of the structurant solution which had been allowed to cool to - 90°C.i The resultant mixture 5 was stirred briefly to achieve complete mixing, poured into commercial 50g stick barrels at approximately 80°C and allowed to cool. The formulations and properties of the sticks are summarised H 0 in Table 9 below. WO 03/059307 PCT/EP02/14525 63 - Table 9 Example No Ex 5.1 EX 5.2 Ingredient % by weight Ex 1.1 Product 1.5 1 Ex 1.2 Prod ■act 1.5 GP-1 4 ISA 29.0 27.0 Finsolv TN 29.0 27.0 Zirconal 50 40.0 40 . 0 Abil EM90 0.5 0.5 Properties Hardness (mm) 27.8 17.1 pay-off (g)at t0 on wool 0.66 0.80 whiteness t=24hr on wool II 17 18 From Table 9, it can be seen that even though the stick in Example 5.1 was comparatively soft for a stick., it had acceptable pay-off and only a low visible deposit. Visually it was slightly translucent. The somewhat harder stick of II Example 5.2 also gave an acceptable pay-off and low visible deposits. 10 15 Example 6 - Clear Emulsion Stick P : In this Example, the general method of making emulsion i i sticks described in Example 5 was followed, preceded by a preparatory s(tep for refractive index matching in order to obtain a translucent emulsion stick. ii In the preparatory step, the refractive indices of the ingredients of the organic and aqueous phases in the emulsion were obtained or measured,; and proportions of those WO 03/059307 PCT/EP02/14525 64 ingredients es such that the indices. The timated, based on calculation and measurement, two phases had roughly matched refractive two phases containingjthe estimated proportions of ingredients were prepared, their refractive indices measured and the proportions of the carrier oils in the continuous (water-immiscible) phase were adjusted to the extent necessary to more closely match the RI of the disperse aqueous phase. 10 15 The Versamid polymer when employed was dissolved simultaneously with the DOPAD. Any silica was incorporated in suspension in a fraction of the water-immiscible oil(s) and any antiperspirant active supplied as a solid was first dissolved in the specified weight of water. In Examples 6 illO and 6.11, a fraction of ISA (7.4 parts for 6.10 and 5.9 parts for 6.11), all of the DC245 and the 20 25 30 Arlacel P135™, were combined in a beaker and warmed to about 40°C to dissolve the Arlacel. The preformed aqueous solution of Reach 908 was then poured into the Arlacel P13 5 solution while stirring with an overhead mixer. The speed of the mixer was increased to 1500 rpm for two minutes to form an emulsion whereupon the aqueous solution forms the internal phase. The emulsion was covered and warmed to 55- 58°C. The DOPAD and the remaining ISA were combined in a ll ■ beaker together with the propane-1,2-diol, di-(propane-1,2- diol), Dowanol TPnB™ and Finsolv TN™ (as appropriate) and heated to 135~140°C on a hotplate, with, stirred to dissolve. the DOPAD. The hotplate was then removed and the solution allowed to cool to 65-70°C without stirring. The resultant solution was then poured into the emulsion and the mixture WO 03/059307 PCT/EP02/14525 65 - stirred briefly to ensure complete mixing. The mixture was then poured into a stick barrel and allowed to cool under ambient condit ions. The formulation and its properties are summarised in Table 10 below, Table 10 - Example No 6.1 6.2 6.3 6.4 6.5 6.6 Ingredients % by weight Ex 1.2 1.5 2.0 2.0 " 1.5 2.0 2.0 ISA 21.14 12.84 18.51 20.92 43.45 42.66 Finsolv TN | 5.71 8.22 5.05 5.65 DC245 i 21.14 26.83 20.44 20.93 11.77 11.56 Glycerol 10.0 17.0 10.0 10.0 Benzyl Alcohc >1 4.61 Zirconal 50 40.0 40.0 40.0 40.0 water 16.52 17.58 Rezal 36GP 24.77 Reach 908 23.71 Abil EM90 0.5 0.5 1.0. 1.0 0.49 0.49 Fragrance ': 1.0 Versamid 93 0 1.0 HDK H3 0RX 1.0 i i Properties■ Hardness (mm1) II 18.6 n/d 13.4 11.9 17.2 14.4 Clarity (% Tj) ll 6.7 n/d n/d n/d n/d 42.0 Clarity (visl score) lal 1 n/d n/d n/d n/d 4 pay-off (g)at; on wool) to 1.39 n/d n/d n/d n/d n/d WO 03/059307 PCT/EP02/14525 - 66 - Example No 6.7 6.8 6.9 6.10 6.11 6.12 Ingredients % by weight Ex 1.2 2.0 2.0 1.5 1.5 1.9 2.0 ISA 41.08 43.05 20.6 21.65 42.7 32.5 Finsolv TN 5.55 3.95 7.4 DC245 11.14 11.67 20.60 21.65 10.6 15.1 Glycerol 10.0 10.0 propane-1,2-diol 4.6 2.1 di(propane-1 diol) 2- 4.1 Dowanol TPnB 4.6 Zirconal 50 4 0.0 40.0 water 17.78 17.78 13.9 14.0 Reach 908 23.71 23.71 '■ 20.7 20.8 Abil EM90 0.49 0.49 0.75 0.75 Arlacel P135 1.0 1.0 Fragrance 1.0 Versamid 93 0 2.0 1.0 1.0 HDK H3 0 0.50 HDK H3 0RX 2.0 HDK HI8 | 0.5 Properties. Hardness (mm)' ll 19.9 17.2 14.8 14.7 17.6 17.1 Clarity (% T), ll 19.0 58.4 0.82 0.74 n/d n/d Clarity (visi score) 1 -i aal i ! -1 7 n/d n/d n/d n/d WO 03/059307 PCT/EP02/14525 67 - Stick Characterisation - Measurement of Properties i) Stick hardness - Penetrometer The hardness solid can be 10 15 20 penetrometer grams) which specified to a flat upper and rigidity of a composition which is a firm determined by penetrometry. If the composition is a softer solid, this will be observed as a substantial lack of any resistance to the penetrometer probe. A suitable procedure is to utilises a lab plant PNT equipped with a Seta wax needle (weight 2.5 has a cone angle at the point of the needle be 9°10' + 15'. A sample of the composition with surface is used. The needle is lowered onto the five seconds Desirably the surface of the composition and then a penetration hardness measurement is conducted by allowing the needle with its holder to drop under a total weight, (i.e. the combined weight of needle and holder) of 50 ,'grams for a period of after which the depth of penetration is noted. test is carried out at a number of points on each sample a'nd the results are averaged. Utilising a test of this nature, an appropriate hardness for use in an open-ended dispensing container is a penetration of less than 3 0 mm in this test, for example in a range from 2 to 30 mm. Preferably the penetration is in a range from 5mm to 20 mm. In a specific protocol for this test measurements on a stick 25 were performed in the stick barrel. The stick was wound up to project from the open end of the barrel, and then cut off l| - to leave a flat, uniform surface. The needle was carefully lowered to the stick surface, and then a "pens t rat "ion hardness measurement was conducted.. This process was 3 0 carried out at six different points on the stick surface. WO 03/059307 PCT/EP02/14525 68 The hardness |jreading quoted is the ^average value of the 6 measurements. ii) Deposition by firm sticks (pay-off) standardised surface is de 5 Another property of a composition is the amount of it which is delivered onto a surface when the composition is drawn across that surface (representing the application of a stick product to human skin), sometimes called the pay-off. To carry out this test of deposition when the composition is a 10 firm stick, able to sustain its own shape, a sample of the composition with standardised shape and size is fitted to apparatus which draws the sample across a test surface under conditions. The amount transferred to the termined as an increase in the weight of the 15 substrate to which it is applied. If desired the colour, opacity or clarity of the deposit may subsequently be determined. A specific procedure for such tests of deposition and whiteness applicable to a firm solid stick used apparatus to apply a deposit from a stick onto a 2 0 substrate under standardised conditions and then measures I! the mean level of white deposits using image analysis. The substrate's used were: a: 12 x 28cm strip of grey abrasive paper (3M™ P800 2 5 WetorDry™ Carborundum paper) b: 12 x 2 8cm strip of black Worsted wool fabric. The substrates were weighed before use. The sticks were previously unused and with domed top surface unaltered. 3 0 The apparatus substrate was comprised a flat base to which a flat attached by a clip at each end. A pillar WO 03/059307 PCT/EP02/14525 - 69 - 10 having a mounting to receive a standard size stick barrel was mounted on an arm that was moveable horizontally across the substrate by means of a pneumatic piston. positioned to standardised stick lateral substrate was The whiteness as described Each stick was kept at ambient laboratory temperature overnight before the measurement was made. The stick was advanced to project a measured amount from the barrel. The barrel was then placed in the apparatus and a spring was biassed the stick against the substrate with a iorce. The apparatus was operated to pass the ly across the substrate eight times. The carefully removed from the rig and reweighed. of the deposit could -subsequently be measured at (v) below. 15 (iii) Whiteness of Deposit The. dep.osits their whitene from the at test (ii) above, were assessed for ss shortly after application (ie within 3 0 minutes) or after an interval of 24 hours approximately. 20 This was done using a Sony XC77 monochrome video camera with a Cosmicar 16mm focal length lens positioned vertically above a black table illuminated from a high angle using fluorescent tubes to remove shadowing. The apparatus was initially calibrated using a reference white card, after the fluorescent tubes had been turned on for long enough to give a steady light output. A cloth or:,Carborundum paper with a deposit there'on from the previous test was placed on the table and the; camera was used to capture an image". An" area 30 of the image of the deposit was selected and analysed using a Kontron IBXs™ image analyser. This notionally divided the WO 03/059307 PCT/EP02/14525 70 - image into a large array of pixels.and measured the grey level of each pixel on a scale of 0 (black) to 255 (white). The average of the grey intensity was calculated. This was a measure of the whiteness of the deposit, with higher numbers indicating a whiter deposit. It was assumed that low numbers show a clear deposit allowing the substrate colour to be seen. I iv Clarity of formulation - Light transmission 10 The translucency of a composition may be. measured by placing a sample of standardised thickness in the light path of a spectrophotometer and measuring transmittance, as a percentage ofii light transmitted in the absence of the gel. 15 This test was carried out using a dual-beam Perkin Elmer methacrylate) temperature o thickness of Lambda 4 0 spectrophotometer. The sample of composition was poured hot into a 4.5 ml cuvette made of poly(methyl-(PMMA) and allowed to cool to an ambient f 20-25°C. Such a cuyette gives a 1 cm 20 thickness of composition. Measurement was carried out at 580 nm, with an identical but empty cuvette in the reference beam of the spectrophotometer, after the sample in the cuvette had been held for 24 hours.- A transmittance measured at any temperature in the range from 20-25°C is 25 usually adequately accurate, but measurement is made at 22°C if more precision is required. 30 v) Clarity of Formulation - Visual assessment score A gel contained within a 1cm thick cuvette-was placed directly on to a sheet of white paper on which 21 sets of figures where printed in black. The size and thickness of WO 03/059307 PCT/EP02/14525 - 71 (the largest, thinnest set) the figures varied systematically and were numbered from -12 thickest set) through 0 to 8 (the smallest The score given to each gel was the highest numbered set which could be read cl'early through the- gel, the higher the number, the higher the clarity. CLAIMS An antiperspirant composition comprising: i) an antiperspirant active material ii) a continuous phase which comprises water-immiscible liquid carrier, and iii) a structurant therein which comprises a cyclodipeptide derivative, hereinafter DOPAD, having II the general formula in which RA represents a carbocyclic or heterocyclic group containing not more than; 2 rings, other than II unsubstituted cyclohexyl. A composition as claimed in claim 1 in which the carbocyclic or heterocyclic group in RA is substituted by at least one alkyl, alkenyl, ether or ester substituent and/or contains at least one degree of ring unsaturation. 72 A c DOPAD other I! omposition as claimed in "claim 1 or 2 in which- RA in represents a six membered ring, optionally, bridged, than unsubstituted cyclfohexyl. A composition as claimed in. any preceding claim in which RA in DOPAD represents ,a substituted carbocyclic satura ted, unsaturated non-aromatic or aromatic ring. II A comp which A composition as claimed in claim 4 in which RA in. DOPAD represents a single ring. osition as claimed in any one of claims 1 to 5 in the ring in RA is a substituted cyclohexyl group. A composition as claimed in any one of claims 1 to 5 in which the ring in RA is a cyplohexenyl group, optionally substituted which substi A composition as claimed in any one of claims 1 to 5 in the ring in RA is a .phenyl group, optionally tuted. J which substi A composition as claimed in any one of claims 1 to 4 in the ring in RA is a naphthenyl group, optionally tuted. A composition as claimed in claim 1 2 or 3 in which RA in DOPAD represents a saturated heterocyclic ring, A comp'osition as claimed in "claim 5 in which the hetero atom iln the ring in Rfl is nitrogen. 73 12. A comp'bsition as claimed in any preceding claim in which the ring in RA is substituted .by at least one alkyl group. 13. A compasition as claimed in claim 12 in which the alkyl group is methyl or isopropyl. 14. A composition as claimed in claim 12 or 13 in which the ring in RA is substituted by t'wo to four alkyl groups. 15. A composition as claimed in claim 12,13 or 14 in which at least one of the alkyl groups .,is methyl. 16. A composition as claimed in claim 15 in which the ring in RA is a lso substituted by an isopropyl group. RA is methyl other. A composition as claimed in claim 16 in which the ring in a cyclohexane or benzene ring substituted by a and an isopropyl group that are para to each A composition as claimed in any- preceding claim in which the ri'ng in RA is substituted by an hydroxyl, ether or ester substituent. 19. A composition as claimed in claim 15 in which the DOPAD is derivable from methyl substituted piperidinol. 20. A composition as claimed-in claim 13 in which the residue RA is derivable from thymol, isopinocamphenol and a 3,5-dialkyl cyclohexanol. ; 74 21. A composition as claimed in' claim 20 in which the 3,5-dialkyl cyclohexanol is 3,5-dimethyl cyclohexanol. 22. A composition as claimed in claim 20 in which the residue Rft is derivable from thymol 23. A composition as claimed in claim 7 in which the residue Rfl is derivable from carveol, 24. A composition as claimed in claim 8 in which the residue RA is derivable from carvacrol 25. A composition as claimed in any preceding claim in which the DOPAD is present at a concentration of from 0.1 to 15% by weight of the composition, 26. A composition as claimed in claim 25 in which the DOPAD is present at a concentration of from 0.3 to 10% by weight of the composition, 27. A composition as claimed in claim 2 6 in which the DOPAD I is present at a concentration of from 0.5 to 3.5% by weight of the composition. 28. A composition as claimed in claim 27 in which the DOPAD II is present at a concentration of from 0.4 to 8% by weight of the continuous phase. 29, A compo'sition as claimed in claim 28 in which the DOPAD II is present at a concentration of from 1.5 to 2.5% by weight pf the continuous phase.' .75 30. A composition as claimed in any one of the preceding claims characterised in that the water-immiscible liquid carrier contains a silicone oil and/or a non-silicone hydrophobic organic liquid .selected from hydrocarbons, hydrophobic aliphatic esters, aromatic esters, hydrophobic alcohols and hydrophobic ethers. 31. A composition as claimed in any one of the preceding claims wherein the water-immiscible carrier liquid contains silicone oil in an amount which is at least 10% by weight of the composition.;, I F j' claims fatty 32. A composition as claimed in any one of the preceding which contains not more than 3% by weight of any alcohol which is solid at 20°C. 33. A composition as claimed in any one of the preceding claims which does not contain more than 3% of any wax material which is solid at !30 C, softens and is molten I :' ■■ and soluble in the water-immiscible liquid at 95°C. 34. A composition as claimed in any preceding claim in which the DOPAD is employed in ^conjunction with a further structurant. 35. A composition as claimed in claim 34 in which the further structurant is an- N-acyl amino acid derivative, and/or an hydroxystearic acid and/or a dibenzylidene alditol. 36. A composition as claimed in claim 35 in which the further structurant is N-lauroyl glutamic acid dibutylamide. 76 which ratio 37. A composition as claimed in ; any of claims 34 to 36 in the further structurant is employed in a weight to DOPAD of from 1: 10 to 10: 1. 38 A composition as claimed in claims 37 in which the further structurant comprises N-lauroyl glutamic acid dibutylamide or 12-hydroxy stearic acid in a weight ratio to DOPAD of from 1: 1 to 6: 1.' 39. A composition as claimed in claim 37 in which the further structurant comprises dibenzylidene sorbitol in a weight ratio to DOPAD of from 1: 3 to 1: 10. 40. A composition as claimed in any preceding claim in which the composition comprises a 'suspension of the cosmetic active in the structured hydrophylic-carrier liquid. 41. A composition as claimed in claim 40 in which the carrier liquid and the suspended cosmetic active have matched refractive indices and has a light transmission of at least 1% II 42. A composition as claimed in 'any one of claims 1 to 39 II ' wherein the composition is ah' emulsion with the cosmetic active in solution in a hydrophilic, preferably water- miscibie, disperse phase. 43. A composition as claimed in claim 42 wherein the disperse phase contains a diol or polyol. 44. A composition as claimed in claim 43 wherein the disperse 77 phase contains glycerol or 12-propane diol, 45, A composition as claimed in any of claims 42 to 44 in which the composition contains from 0.1% to 10% by weight of a nonionic emulsifier. 46. A composition as claimed in claim 45 in which the emulsifier is an alkyl dimethicone copolyol. 47. A composition as claimed in, any of claims 42 to 46 in which the refractive indices of the disperse and continuous phases of the emul'sion are matched. 48 A cosmetic composition as claimed in any preceding claim in which the cosmetic active is an antiperspirant or deodoE ant active. 49. A composition as claimed in claim 48 in which the antiperspirant active comprises an aluminium and/or zirconium halohydrate, an activated aluminium and/or. zirconium halohydrate, or an aluminium and/or zirconium complex or an activated aluminium and/or zirconium complex. 50. A composition as claimed in claim 48 in which the complex contains both aluminium and zirconium. 51. A comp claims osition as claimed in, any one of the preceding which contains from 5 to 40% by weight of the antiperspirant active. 78 52. An cosmetic product comprising a dispensing container having urging I or ape an aperture for delivery of a stick, means for the contents of the container to the said aperture rtures, and a composition as claimed in any one of the preceding claims accommodated within the container. 53. A product as claimed in claim 52 wherein the composition ll [- is a firm gel such that a penetrometer needle with a cone angle of 9 degrees 10 minutes, drops into the gel for no more than 30mm when allowed to drop under a total weight I! '; of 50 grams for 5 seconds. 54 A process for the production of a composition as claimed in any jone of claims 1 to 51 comprising the steps of:- ai) incorporating into a water-immiscible liquid carrier a structurant which is one or more structurant compounds II as defined in claim 1, a2) mixing the liquid carrier with a solid or a disperse liquid phase comprising cosmetic active in particulate or dissolved form to be suspended in the water- immiscible liquid! a3) heating the liquid carrier or a mixture containing it to an elevated temperature at which the structurant is dissolved or dispersed - in the water-immiscible liquid carrier steps al) a2) and a3) being conducted in any order followed by: bl) introducing the mixture into a mould which I! : preferably is a dispensing container, and then cl) cooling or permitting the > mixture to cool to a 79 55, 56, temperature at which the liquid carrier is solidified. A process as claimed in claim 54 in which the DOPAD structurant is dissolved in one component of the liquid hydrophobic carrier at- a temperature that is higher than that attained by the remainder of hydrophobic carrier. i A proc'ess as claimed in claim 54 or 55 which includes a step of pouring the mixture at elevated temperature into a dispensing container and allowing it to cool therein so as to produce a product as claimed in claim 51 or 52, 57. A cosmetic method for preventing or reducing perspiration on human skin comprising topically applying to the skin a composition as claimed in any rone of claims 1 to 50. 58. A new compound, a cyclodipeptide derivative (DOPAD) as described in any one of claims 1 to 24 wherein RA in the said compound is not residue of menthol. 59. A cyclodipeptide as claimed' in claim 58 in which RA comprises a saturated or; unsaturated 6 membered carbocyiclic ring substituted '! by two CI to C3 alkyl or I alkenyU substituents. 6CK A cycl the res odipeptide as claimed in claim 59 in which RA is idue from thymol. 80 1. A process for making cyclopepeptide derivative comprising the step of reacting DOPA acid (DOPAA) having the formula 0 with at least an equimolar1' amount of an alcohol of II formula RAOH in which Rft is as defined in claim 58 in the |j presence of at least 0.5 moles of promoter per mole of DOPA acid in a reaction medium comprising dimethyl sulphoxide. " 2. A process as claimed in claim161 in which the promoter is II a carbonyldiimidazole. 3. A process as claimed in clainr 61 or 62 in which the mole ratio of DOPAA to the alcohol RAOH is from 2: 1 to 7: 1. 4. A process as claimed in any of claims 61 to 63 employing from 0 5 to 2 moles of promoter per mole of DOPAA, 65. A process as claimed in any of claims 61 to 64 which is conducted at a temperature of from 4 0 to 60.°C for a period of from 9 to 24 hours, 66. A gel comprising a water-immiscible oil gelled with an effective concentration of a cyclodipeptide derivative (DOPAD) described in any one of claims 1 to 24 other than the compound in which RA is the residue of menthol, optionally in conjunction with a further structurant. 82

Documents:

00371-mumnp-2004-cancelled pages(21-02-2006).pdf

00371-mumnp-2004-claims(granted)-(21-02-2006).doc

00371-mumnp-2004-claims(granted)-(21-02-2006).pdf

00371-mumnp-2004-correspondence 1(14-11-2005).pdf

00371-mumnp-2004-correspondence 2(12-01-2007).pdf

00371-mumnp-2004-correspondence(ipo)-(31-08-2007).pdf

00371-mumnp-2004-form 18(14-11-2005).pdf

00371-mumnp-2004-form 1a(07-07-2004).pdf

00371-mumnp-2004-form 2(granted)-(21-02-2006).doc

00371-mumnp-2004-form 2(granted)-(21-02-2006).pdf

00371-mumnp-2004-form 3(07-07-2004).pdf

00371-mumnp-2004-form 5(07-07-2004).pdf

00371-mumnp-2004-form-pct-ipea-409(07-07-2004).pdf

00371-mumnp-2004-form-pct-isa-210(07-07-2004).pdf

00371-mumnp-2004-power of attorney(15-02-2006).pdf

371-MUMNP-2004-CORRESPONDENCE(8-2-2012).pdf