Title of Invention	A COMPOSITION EFFECTIVE IN THE REMOVAL OF ECTOPARASITES AND A PROCESS FOR THE PREPARATION THEREOF
Abstract	This invention relates to a composition effective in the removal of ectoparasites comprising a) Pediculicidal active agent, typically from 0.02% to 2.5% b) Vegetable oil, typically from 0.1% to about 99.98% c) Mineral oil, typically from 0% to about 99.98% d) Substituted methylene dioxyphenyl compound, typically from 0% to 5% e) Neem extract, typically from 0% to 5%.

Full Text

COMPLETE SPECIFICATION SECTION 10 TITLE "A COMPOSITION EFFECTIVE IN THE REMOVAL OF ECTOPARASITES AND A PROCESS FOR THE PREPARATION THEREOF*. APPLICANT MARICO INDUSTRIES LIMITED, an Indian company of Rang Sttarda, K.C. Marg, Bandra Reclamation, Bandra West, Mumbai-400 050, Maharasthra, INDIA. The following specification particularly describes and ascertains the nature of this invention and the manner -2-Field of the Invention This invention relates to a composition effective in the removal of ectoparasites, more particularly for the extermination of lice and to a process for the preparation of said compositon. Background of the Invention: -Pediculus humanus capitis is an ectoparasite that causes Pediculosis, a term used to describe the condition arising from its infestation. As the lice feed on human skin and blood, they inject their digestive juices and fecal material into the skin which along with the puncture wound itself, cause skin irritation and lesions from the resulting scratching. Lice are also known to be vectors of certain diseases, such as exanthematic or epidemic typhus and recurrent fever. The adult female louse has a life span of about one month, in which it lays up to ten nits a day that are firmly attached to hair through an excreted cement. The nits hatch to release instars in about 7-9 days, which become mature adults in another week. Effective control of Hce requires an approach that eliminates all 3 stages of the louse life cycle. -3- Most currently utilised options for an effective control of lice involve the application of pediculicides, which are toxic pharmaceutical agents that, when interaalized, poison and kill lice. Examples of such pediculicidal agents used to treat lice are "described in EP 0191236 and U.S. Pat. No. 5,288,483. Typically, such pediculicidal agents enter via the respiratory spiracles, and once inside the louse, interfere with the function of a critical metabolic or physiological pathway, leading to death. Malathion, for example, inhibits acetylcholinesterase, disrupting signaling in the nervous system. Some of these compounds are also toxic to humans, for e.g., there are reports in the medical literature, that children treated with lindane have developed seizures. Many of these compounds also have unpleasant odors or other undesirable properties, causing noncompliance by the patient, leading to re-infestation of the individual, and spreading of the infestation to others. In addition, the harshness of these agents make them unsuitable for use as prophylactics. The removal of nits has typically been done by hand using special fine-tooth combs. U.S. Pat. No. 4,927,813 teaches compositions containing formic acid that facilitate removal of nits from the hair; however, formic acid is a known caustic agent which itself could cause skin irritation. -4- Use of combing alone to treat head lice is not completely effective-because the lice can hold onto the hair shafts using their claws or escape by crawling away from the area being combed. Besides, this method is labor intensive requiring daily combing, is painful, and is unpleasant since the lice are active, visible and crawling. Home remedies such as application of corn oil, olive oil, eucalyptus oil, neem oil, coconut oil, mayonnaise, or petroleum jelly for a period of time sufficient to Idll the lice (e.g. overnight) are by themselves not completely effective. Heat has also been suggested as a means of killing head lice but has not been effective, due in part to the fact that crawling lice will rapidly move away from the heat source. Moreover, the temperatures needed to kill the lice, typically 60 degrees Celsius or higher, can burn or scald the scalp. Use of heat in conjunction with pediculicidal compositions is discouraged because some of the solvents used in the pediculicidal compositions are inflammable at the temperatures necessary to kill the lice and the heat may additionally degrade the active pediculicidal agents as well. -5- Use of aqueous based preparations which have been widely covered7 in the state ofithe art through various patents have some limitation due to the "immersion refe" exhibited by lice, whereby the lice become immobilized as a consequence of reflexes thatlflias evolved to avoid suffocation. The lice remain immobilized while in contact with the pediculostatic or pediculicidal agent in its wet form, and do not recover from the immersion reflex once the agent has been dried onto the lice. U.S. patent No. 6,265,384 teaches that the immersion reflex is a self-preservation behavior that lice have evolved to protect themselves agamst drowning when, through actions of the host, they are immersed in water. Lice are obligate air breathers and cannot derive oxygen when underwater; the immersion reflex allows them greatly to increase the amount of time that they can survive without access to air. During submersion, the spiracles and tracheoles, through which lice breath, become blocked by water. As the lice become anoxic, they rapidly switch into a state of profound suspended animation, decreasing their need for oxygen, thus prolonging their survival. They become completely immobile, unresponsive to stimuli, and even cease gut motility. If the reflex continues too long, however, the lice eventually run completely out of oxygen and die from anoxia. This "immersion reflex" exhibited by the lice sometimes prevent the pediculostatic or pediculocidal agent from entering into the lice thereby impacting its efficacy. -6-Prior art teaches the use of topical agents that are well known to killllic|^suGji as natural \ pyrethrins, pyrethroids, permethrin, lindane, malathion, carbaryl^vivermegtjn and"? combinations thereof. These agents, once internalized, typically target and iirterfere with, i specific components of metabolic or other physiologic pathways, leading to death of the organism. Prior art also teaches that efficacy of the various aqueous based formulations have been reduced by the "immersion effect" which is a normal endogenous behavioral reflex exhibited by the lice to protect themselves from drowning, when, through the actions of the host, they are immersed in water, wherein the metabolic activity of the lice is drastically reduced thereby reducing the penetration of the pediculicidal agent. Objects of the invention: An object of the invention is to propose a composition for effective control of ectoparasites, more particularly for the extermination of lice, and to a process for the preparation of said composition. Another object of the invention is to propose a composition for effective control of nits. Yet another object of the invention is to propose a composition for effective control of ectoparasites, more particularly for the extermmatioa office. -7- Still another object of the invention is to propose a composition for effectivle conlrof of nits. Summary of the Invention: According to this invention there is provided a synergistic composition effective in controlling ectoparasites, more particularly for the extermination of lice, comprising severally or in certain combinations a) pediculicidal active agent, more particularly permethrin, b) vegetable oil, c) mineral oil, d) substituted methylene dioxyphenyl compound, more particularly piperonyl butoxide e) neem extract. Further according to this invention there is provided a process for manufacture of a hair oil composition comprising a) Pediculicidal active agent, typically from 0.02% to 2.5% b) Vegetable oil, typically from 0.1% to about 99.98% c) Mineral oil, typically from 0% to about 99.88% d) Substituted methylene dioxyphenyl compound, typically from 0% to 5% e) Neem extract, typically from 0% to 5% obtained by mixing the said ingredients with a stirrer at a temperature range from but not limited to 25 - 60 degrees centigrade for a period of but not limited to 60 minutes, applying the said composition for a period ranging from 5 minutes to 8 hours but not limited to this duration. -8- Repeated application of the above composition at an interval not greater than 7 days for a period of 1 month is effective in controlling the lice infestation including nits and instars. Non-limiting examples of suitable pediculicidal agents include natural or other pyrethrins, pyrethroids, permethrins, phenothrins and combinations thereof Non-limiting examples of vegetable oils include coconut oil, cotton seed oil, groundnut oil, linseed oil, olive oil, mahua oil, rapeseed oil, poppy seed oil, saffiower oil, til oil, soyabean oil, corn oil, palm oil, palm kernel oil, palmolein, sunflower seed oil, rice bran oil, water melon seed oil, taramira oil, niger seed oil, almond oil. Non-limiting examples of Mineral oil include light and heavy liquid paraffin of which the most preferred option is light liquid paraffin having a viscosity of about 14 cps. Non-limiting example of substituted methylene dioxyphenyl compound is piperonyl butoxide. Neem extract comprises oil soluble extract of neem obtained by but not limited to extraction in a suitable vegetable oil or mineral oil. -9- The following examples are illustrative of the practice of the invention, but the invention is not limited to the specific illustrations given. It is expected that one skilled in the relevant art would arrive at other variations, which although differing from the following examples, do not depart from the spirit and scope of the invention as described and claimed herein. Example 1. 50g of Perraethrin were mixed with 5 litres of coconut oil at 30 degrees centigrade for a period of 30 minutes under high speed stirring at 200 rpm to obtain a premix which was checked for complete mixing. Resultant premix was added to 94.95 litres of coconut oil containing suitable perfume, and stirred for a further period of 30 minutes. Batch was tested for uniformity of composition. Example 2. 50g of Permethrin and 150g of Piperoriyl butoxide were mixed with 5 litres of coconut oil at 30 degrees centigrade for a period of 30 minutes under high speed stirring at 200 rpm to obtain a premix which was checked for complete mixing. Resultant premix was added to 94.8 litres of coconut oil containing suitable perfbmej -antioxidant and colour and stirred for a further period of 30 minutes. Batch was tested for uniformity of composition. -10- Example 3. 50g of Permethrin and 150g of Piperonyl butoxide and lOOg of neem extract were mixed with 5 litres of coconut oil at 30 degrees centigrade for a period of 30 minutes under high speed stirring at 200 rpm to obtain a premix which was checked for complete mixing. Resultant premix was added to 94.8 litres of coconut oil containing suitable perfume, antioxidant and colour and stirred for a further period of 30 minutes. Batch was tested for uniformity of composition and compliance as per the following specifications- Results based on 1 hour of exposure. N=30 lice for each sample. In-vitro evaluations were performed to test the efficacy using a mixed population of head lice that were harvested and subjected to the test within one hour using the standardised test procedure. Results were as follows- -11- Example 4. 50g of Permethrin, 500g of neem extract and 50g of Piperonyl butoxide wfere mixed with: 5 litres of coconut oil at 45 degrees centigrade for a period of 30 minutesfeuider highf speed stirring at 200 rpm to obtain a premix which was checked for complefe^iabang. Resultant premix was added to 93.9 litres of coconut oil containing 500g camphor, suitable perfume, antioxidant and colour and stirred for a further period of 30 minutes for uniformity of composition. 10 ml of the sample was applied evenly divided into 4 parts on the 2 tempo-parietal regions, the frontal region and the posterior area of the scalp. The scalp was left undisturbed and combed after 30 minute and 60 minute intervals using 10 strokes with a wide toothed comb followed by 20 strokes with a narrow toothed comb. Specifications of the comb are as follows- In-vivo evaluation was done for the following- 1. Base oil composition not containing Permithrin, Piperonyl butoxide and Neem (Group A) 2. Base oil containing 0.05% Permithrin and 0.05% Piperonyl butoxide (Group B) 3. Sample as per above described in Example 4 (Group C) 4. Base oil containing 0.5% Neem (Group D) -12- In-vivo evaluation was done for volunteers having moderate to heavy lice infestation and results were obtained after subtracting baseline counts. Statistical evaluation of the data including ANNOVA evaluation were done. Results of the in-vivo study were as follows- Consolidated data of lice dislodgement after 30 and 60 minutes study The above data and tables are self-explanatory in terms of the synergy involved. Other examples of the invention are as follows- -13-Example 5. 50g of Permethrin, lOOg of neem extract and 150g of Piperonyl butolgdeiwere mixed with 5 litres of coconut oil at 45 degrees centigrade for a period of 30 mmutes,under high speed stirring at 200 rpm to obtain a premix which was checked for complete mixing. Resultant premix was added to 94.5 litres of coconut oil containing 200g camphor, suitable perfume, antioxidant and colour and stirred for a further period of 30 minutes for uniformity of composition. 10 ml of the sample was applied evenly divided into 4 parts on the 2 tempo-parietal regions, the frontal region and the posterior area of the scalp. The scalp was left undisturbed and combed after 30 minute and 60 minute intervals using 10 strokes with a wide toothed comb followed by 20 strokes with a narrow toothed comb. Example 6. 50g of Permethrin, 50g of neem extract and 150g of Piperonyl butoxide were mixed with 5 litres of coconut oil at 45 degrees centigrade for a period of 30 minutes under high speed stirring at 200 rpm to obtain a premix which was checked for complete mixing. Resultant prefnix was added to a mixture of 60 liters of coconut oil, 34.1 liters mineral oil, 200g camphor, suitable perfume, antioxidant and colour and stirred for a further period of 30 minutes for uniformity of composition. 10 ml of the sample was applied evenly divided into 4 parts on the 2 tempo-parietal regions, the frontal region and the posterior area of the scalp. The scalp was left undisturbed and combed after 30 minute and 60 minute intervals using 10 strokes with a wide toothed comb followed by 20 strokes with a narrow toothed comb. -14- Example 7. 50g of Permethrin, 100g of neem extract and 250g of Piperonyl butoxide were mixed with 5 litres of coconut oil at 30 degrees centigrade for a period of 30 minutes under high speed stirring at 200 rpm to obtain a premix which was checked for complete mixing. Resultant premix was added to a mixture containing 35 liters of coconut oil, 59.6 liters mineral oil, suitable perfume, antioxidant and colour and stirred for a further period of 30 minutes for uniformity of composition. 10 ml of the sample was applied evenly divided into 4 parts on the 2 tempo-parietal regions, the frontal region and the posterior area of the scalp. The scalp was left undisturbed and combed after 30 minute and 60 minute intervals using 10 strokes with a wide toothed comb followed by 20 strokes with a narrow toothed comb. Example 8. 20g of Permethrin, lOOg of neem extract and 50g of Piperonyl butoxide were mixed with 5 litres of coconut oil at 30 degrees centigrade for a period of 30 minutes under high speed stirring at 200 rpm to obtain a premix which was checked for complete mixing. Resultant premix was added to a mixture containing 35 liters of coconut oil, 59.8 liters mineral oil, suitable perfume, antioxidant and colour and stirred,for a further period of 30 minutes for uniformity of composition. 10 ml of the sample was applied evenly divided -15- into 4 parts on the 2 tempo-parietal regions, the frontal region and the posterior area of the scalp. The scalp was left undisturbed and combed after 30 minute and 60 minute intervals using 10 strokes with a wide toothed comb followed by 20 strokes with a narrow toothed comb. Example 9. 50g of Permethrin, 50g of neem extract and 150g of Piperonyl butoxide were mixed with 5 litres of sunflower oil at 45 degrees centigrade for a period of 30 minutes under high speed stirring at 200 rpm to obtain a premix which was checked for complete mixing. Resultant premix was added to a mixture of 60 liters of sunflower oil, 34.5 liters mineral oil, 200g camphor, suitable perfume, antioxidant and colour and stirred for a further period of 30 minutes for uniformity of composition. 10 ml of the sample was applied evenly divided into 4 parts on the 2 tempo-parietal regions, the frontal region and the posterior area of the scalp. The scalp was left undisturbed and combed after 30 minute and 60 minute intervals using 10 strokes with a wide toothed comb followed by 20 strokes with a narrow toothed comb. -16-Example 10. 150g of Permethrin, 500g of neem extract and 150g of Piperonyl butoxide were mixed with 5 litres of groundnut oil at 45 degrees centigrade for a period of 30 minutes under high speed stirring at 200 rpm to obtain a premix which was checked for complete mixing. Resultant premix was added 94.0 liters mineral oil, 200g camphor, suitable perfume, antioxidant and colour and stirred for a further period of 30 minutes for uniformity of composition. 10 ml of the sample was applied evenly divided into 4 parts on the 2 tempo-parietal regions, the frontal region and the posterior area of the scalp. The scalp was left undisturbed and combed after 30 minute and 60 minute intervals using 10 strokes with a wide toothed comb followed by 20 strokes with a narrow toothed comb. Example 11. 50g of Permethrin, 500g of neem extract and 50g of Piperonyl butoxide were mixed with 5 litres of ricebran oil at 45 degrees centigrade for a period of 30 minutes under high speed stirring at 200 rpm to obtain a premix which was checked for complete mixing. Resultant premix was added 94.4 liters mineral oil, 200g camphor, suitable perfume, antioxidant and colour and stirred for a further period of 30 minutes for uniformity of composition. 10 ml of the sample was applied evenly divided into 4 parts on the 2 tempo-parietal regions, the frontal region and the posterior area of the scalp. The scalp was left undisturbed and combed after 30 minute and 60 minute intervals using 10 strokes with a wide toothed comb followed by 20 strokes with a narrow toothed comb. -17-Example 12. 150g of Permethrin, lOOg of neem extract and 150g of Piperonyl butoxide were^mked.-,^ ; with 15 litres of coconut oil at 45 degrees centigrade for a period of 30 minutes under high spefd stirring at 200 rpm to obtain a premix which was checked-for.complete mixing. Resultant premix was added 84.6 liters mineral oil, 200g camphor, suitable perfume, antioxidant and colour and stirred for a further period of 30 minutes for uniformity of composition. 10 ml of the sample was applied evenly divided into 4 parts on the 2 tempo-parietal regions, the frontal region and the posterior area of the scalp. The scalp was left undisturbed and combed after 30 minute and 60 minute intervals using 10 strokes with a wide toothed comb followed by 20 strokes with a narrow toothed comb. Example 13. 20g of Permethrin, 500g of neem extract and 50g of Piperonyl butoxide were mixed with 25 litres of sunflower oil at 45 degrees centigrade for a period of 30 minutes under high speed stirring at 200 rpm to obtain a premix which was checked for complete mixing. Resultant premix was added 74.2 liters mineral oil, 200g camphor, suitable perfume, antioxidant and colour and stirred for a further period of 30 minutes for uniformity of composition. 10 ml of the sample was applied evenly divided into 4 parts on the 2 tempo-parietal regions, the frontal region and the posterior area of the scalp. The scalp was left undisturbed and combed after 30 minute and 60 minute intervals using 10 strokes with a wide toothed comb followed by 20 strokes with a narrow toothed comb. -17- Example 14. lOOg of Permethrin, 500g of neem extract and lOOg of Piperonyl butoxide were mixed with 15 litres of sunflower oil at 45 degrees centigrade for a period of 30 minutes under high speed stirring at ,200 rpm to obtain a premix which was checked for complete mixing. Resultant premix was added 84.1 liters mineral oil, 200g camphor, suitable perfume, antioxidant and colour and ^stirred for a further period of 30 minutes for uniformity of composition. 10 ml of the sample was applied evenly divided into 4 parts on the 2 tempo-parietal regions, the frontal region and the posterior area of the scalp. The scalp was left undisturbed and combed after 30 minute and 60 minute intervals using 10 strokes with a wide toothed comb followed by 20 strokes with a narrow toothed comb. -19-WE CLAIM: 1. A composition effective in the removal of ectoparasites comprising a) Pediculicidal active agent, typically from 0.02% to 2.5% b) Vegetable oil, typically from 0.1% to about 99.98% c) Mineral oil, typically from 0% to about 99.88% \ d) Substituted methylene dioxyphenyl compound, typically from 0% to 5% i \ e) Neem extract, typically from 0% to 5% 2. A composition as claimed in claim 1, wherein the said pediculicidal active agent is selected from natural or other pyrethrins, pyrethroids, permethrins, phenothrins and combinations thereof. 3. A composition as claimed in claim 1, wherein the said" vegetable includes coconut oil, cotton seed oil, groundnut oil, linqeed oil, olive oil, mahua oil, rapeseed oil, poppy seed oil, safflower oil, til oil, soyabean oil, corn oil, palm oil, palm kernel oil, » palmolein, sunflower seed oil, rice bran oil, water melon seed oil, taramira oil, niger seed oil, almond oil and combinations thereof. 4. A composition as claimed in claim 1, wherein the said mineral oil is selected from light or heavy liquid paraffin or combinations thereof. -20- 5. A composition as claimed in claim 1, wherein the said substitued methylene dioxyphenyl compound is piperonyl butoxide. 6. A compos^ipn as claimed in claim 1, wherein the said Neem extract comprises oil soluble Extract of neem obtained by extraction in a vegetable oil comprising any of coconut oil, cotton seed oil, groundnut oil, linseed oil, olive oil, mahua oil, rapeseed oil, poppy seed oil, safflower oil, til oil, soyabean oil, corn oil, palm oil palm kernel oil, palmolein, sunflower seed oil, rice bran oil, water melon seed oil, taramira oil, niger seed oil, almond oil or mineral oil or combinations thereof. 7. A process for producing a composition effective in the removal of ectoparasites comprising a) Pediculicidal active agent, typically from 0.02% to 2.5% b) Vegetable oil, typically from 0.1% to about 99.98% c) Mineral oil, typically from 0% to about 99.88% d) Substituted methylene dioxyphenyl compound, typically from 0% to 5% e) Neem extract, typically from 0% to 5% obtained by mixing the said ingredients with a stirrer at a temperature range of 25 -60 degrees centigrade. -21- 8. A process as claimed in claim 7, wherein the said pediculicidal active agent is selected from natural or other pyrethrins, pyrethroids, permethrins, phenothrins and combinations thereof. 9. A process as claimed in claim 7, wherein the said vegetable includes coconut oil, cotton seed oil, groundnut oil, linseed oil, olive oil, mahua oil, rapeseed oil, poppy seed oil, safflower oil, til oil, soyabean oil, corn oil, palm oil, palm kernel oil, palmolein, sunflower seed oil, rice bran oil, water melon seed oil, taramira oil, niger seed oil, almond oil and combinations thereof. 10. A process as claimed in claim 7, wherein the said mineral oil is selected from light or heavy liquid paraffin or combinations thereof 11. A process as claimed in claim 7, wherein the said substituted methylene dioxyphenyl compound is piperonyl butoxide. -22- 12. A process as claimed in claim 7, wherein the said Neem extract comprises oil soluble extract of neem obtained by extraction in a vegetable oil comprising any of coconut oil, cotton seed oil, groundnut oil, linseed oil, olive oil, mahua oil, rapeseed oil, poppy seed oil, safflower oil, til oil, soyabean oil, corn oil, palm oil, palm kernel oil, palmolein, sunflower seed oil, rice bran oil, water melon seed oil, taramira oil, niger seed oil, almond oil or mineral oil or combinations thereof. 13. A composition effective in the removal of ectoparasites substantially as herein described. 14. A process for producing a composition effective in the removal of ectoparasites substantially as herein described. DATED THIS 9™ DAY OF OCTOBER, 2002.

Documents:

960-mum-2001-claims(complete)-(14-10-2002).pdf

960-mum-2001-claims(granted)-(14-10-2002).pdf

960-mum-2001-claims(granted)-(14-9-2002).doc

960-mum-2001-claims(granted)-(21-2-2008).pdf

960-MUM-2001-CORRESPONDENCE(24-1-2011).pdf

960-mum-2001-correspondence(26-10-2007).pdf

960-mum-2001-correspondence(3-10-2001).pdf

960-mum-2001-correspondence(ipo)-(26-10-2006).pdf

960-mum-2001-correspondence(ipo)-(7-4-2008).pdf

960-MUM-2001-CORRSPONDENCE(13-7-2010).pdf

960-mum-2001-description(complete)-(14-10-2002).pdf

960-mum-2001-description(granted)-(21-2-2008).pdf

960-mum-2001-description(provisional)-(3-10-2001).pdf

960-mum-2001-form 1(13-11-2002).pdf

960-mum-2001-form 1(3-10-2001).pdf

960-mum-2001-form 18(12-5-2005).pdf

960-mum-2001-form 2(complete)-(14-10-2002).pdf

960-mum-2001-form 2(granted)-(14-10-2002).pdf

960-mum-2001-form 2(granted)-(14-9-2002).doc

960-mum-2001-form 2(granted)-(21-2-2008).pdf

960-mum-2001-form 2(provisional)-(3-10-2001).pdf

960-mum-2001-form 2(title page)-(complete)-(14-10-2002).pdf

960-mum-2001-form 2(title page)-(granted)-(21-2-2008).pdf

960-mum-2001-form 2(title page)-(provisional)-(3-10-2001).pdf

960-mum-2001-form 3(3-10-2001).pdf

960-mum-2001-form 4(14-10-2002).pdf

960-mum-2001-form 5(13-11-2002).pdf

960-mum-2001-form 5(14-10-2002).pdf

960-mum-2001-power of attorney(13-11-2002).pdf

960-mum-2001-power of attorney(13-11-2003).pdf

960-MUM-2001-POWER OF ATTORNEY(8-3-2007).pdf

960-MUM-2001CORRESPONDENCE(09-11-2009).pdf