Title of Invention

A DOSAGE FORM CONTAINING POWER OF NUT KERNEL OF CAESALPINIA BONDUC(L.)ROXB. AND PROCESS OF ITS PREPARATION

Abstract

An oral dosage form, including a capsule, and a process of preparing the same from seed kernel powder of Cesalpinia bonduc (L.) Roxb. has been described for treatment of diabetes and diabetic disorders. The process includes specialized device for removing seed coat from intact seed kernels, rejecting the kernels affected by insects and pets, powdering them and preparing an oral dosage form from the seed kernel powder

Full Text

COMPLg-TE AFTER PROVISIONAL LEFT OH A FORM 2 THE PATENTS ACT. 1970 (39 of 1970) & THE PATENS RULES, 2003 COMPLETE SPECIFICATION [See section 10, Rule 13] A MEDICINAL COMPOSITION OF NUT KERNEL OF Caesalpinia bonduc (L.) Roxb. FOR DIABETES IN MAMMALS; DIXIT SHAMKANT PRABHAKAR AN INDIAN NATIONAL OF 15, MUKTAI, MODKESHWAR MARG, NEAR BAPU BUNGLOW, INDIRA NAGAR, NASHIK 422009, MAHARASHTRA, INDIA, AND KANK KISHOR LAXMAN AN INDIAN NATIONAL OF 4, JASH CO-OP. HSG. SOC, OPP. SHRIJAY NAGAR, INDIRANAGAR, NASHIK 422 009, MAHARASHTRA, INDIA. THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED. TECHNICAL FIELD This invention relates to a process and a product of preparing dosage form from Caesalpinia bonduc (L) Roxbjn the treatment of diabetes. BACKGROUND OF THE INVENTION Caesalpinia bonduc (L.) Roxb, a hedge plant is popularly known world wide as "Nicker Nut" or in India in many Indian languages by various names including Kant karanj / kuberakshi and in State of Maharashtra in local language Marathi as "Sagargota". In Ayurveda, the Indian traditional system of therapy to treat diseases based predominantly on use of medicinal herbs, this plant is a valuable medicine prescribed as an effective remedy for many diseases and physical disorders in human beings described in Ayurveda under the names "Cough", "Wata", "Prameha", and against worms, leprosy, fever etc. It is also prescribed in The Indian Materia Medica for treatment in simple, continued and intermittent fevers, asthma, colic disorders etc. The above mentioned nuts are antipyretic, antispasmodic, tonic, antihelementic and fabrifuge. Powder of the seeds is considered as tonic. The seeds of the plant are also known to be used in the treatment of fevers, asthma, colic disorders and also diabetes. It has been reported by Ayurvedic medicine practioners {Vaidyas) that its oral administration lowers the blood sugar level and even reduces risk of other physical damages that generally occur in diabetic patients. It is claimed to be equally as effective as its allopathic counterparts in control of this disorder and also acts as a tonic. In Ayurvedic practice of using seeds for diabetes, the nuts of Caesalpinia are required to be collected either from the wild or the seeds can be purchased 2 .from the market. The plant is a thorny climber. It has sharp spines all over the plant including the cover of the pods containing the seed. The seed available in the market is generally collected by local tribals from the wild. It is preferred to collect the seeds from authentic source and the large size seed. The hard seed coat is required to be removed, and the kernel is made into a paste of fine particles by rubbing the kernel held in hand by reciprocating or circular motion repeatedly against a grinding stone or against a rough surface in appropriate quantity of water or any alternative liquid suitable for ingestion and administer this extremely bitter paste by oral route by licking it as such or with some taste masking or taste modifying agents to make its bitterness bearable. However, the paste is so much bitter and the smell of the paste so offensive that even the person making the paste gets a feel of vomiting and patient compliance with such a remedy was seen to be practically absent. This was one major hurdle in the use of the seeds of Cesalpinia in the treatment. It must be mentioned here that no diversion in fundamental principles of a method of production of a remedy is permitted in Ayurveda. Consequently, the treatment of diabetes as known in prior art as per Ayurveda has been limited / confined to making a paste by rubbing against a grinding stone / a rough surface in a liquid; and this method is not amenable for commercial production and consequently this very useful remedy has remained outside the reach of those who need it, except a few who could produce such a paste manually and take it orally. This was another hurdle in use of Caesalpinia seeds for diabetes treatment. Other logical method to use of medicinal plants applying modern science and technology comprises extraction of the active principles and making pharmaceutical^ applicable compositions from them in suitable dosage forms. 3 This route has so far yielded dismal results in case of this plant. It has been found that extraction by known methods in every conceivable solvent has resulted in extracts which do not show the efficacy against diabetes (Chopra "I. D.of I. pp 307-308 as mentioned in "Indian Materia Medica with Ayurvedic, Unani and home remedies" page no. 227) which is shown by its paste prepared by above described traditional manual process. This has further aggravated difficulties in evolving a practical method of utilization Commercial application of medicinal properties of Caesalpinia bonducjs thus on a hold so far awaiting solution of above problems. SUMMARY OF THE INVENTION This invention relates to developing a process as well as a product from seed kernel of Caesalpinia bonduc for treatment of diabetes. This invention for the first time discloses that seed kernel powder of Caesalpinia bonducjs an effective remedy against diabetes. This invention also discloses a process for production of powder of kernels of this plant. The process of invention also discloses a device comprising a solid block, preferably made in wood, having a depression to hold an individual seed which is hit with a hammer with a judicious strength just enough to crack the seed coat, remove the cracked seed coat, separate the kernel from the pieces, inspect the kernel for freeness from insects and pests and select sound ones for production of the powder. Further, this invention has for the first time made it possible to use capsule or a coated tablet or an equivalent oral dosage form from kernel powder in which the powder of kernel of Caesalpinia is covered by a barrier which shall make it possible to swallow the extremely bitter oral dosage form without exposing its bitterness in the mouth. 4 PRIOR ART Herbal formulations for treatment of diabetes are disclosed in following patent documents. In a US Patent No. 7,014,872 the present invention relates to a herbal health protective, promotive and disease preventive nutraceutical herbal formulation(s) for diabetics, and also relates to a process for the preparation of a herbal health protective, promotive and disease preventive nutraceutical herbal formulation as food supplement to ameliorate the general health of diabetics, said formulation comprises the base product of microwave roasted seed powders mixture from selected genera of Glycine, Cicer, Phaseolus, Cyamompsis, Mucuna, Hordeum, Amaranthus and Fagopyrum, fortified with herbs/medicinal plants used are selected from the genera of Gymnema, Momordica, Syzgium, Pterocarpus, Trigonella, Cinnamomum, Withania, Coccinia, Pueraria, Asparagus, Boerhaavia and Aegle and also some other ingredients like Piper longum, Chlorophytum tuberosum, Curcuma longa and Elettaria cardamomum were also added to get the final nutraceutical product(s); the nutraceuticals are with optimum nutrition, non toxic, natural herbal plant products, easy to digest, have health protective and promotive properties to ameliorate the general health and vigor of diabetics. In a US Patent No. 5,886,029 a medicinal composition is provided for treatment of diabetes in a human subject. The medicinal composition of the invention induces a significant reduction in serum glucose due to the regeneration of pancreatic islet cells. A medicinal composition according to the invention necessarily includes a pharmacologically significant quantity of (-)epicatechin augmented with a comparable amount of gymnemic acid. For best results smaller quantities of Cinnamomum tamala, Syzygium cumini, Trigonella foenum graceum, Azardichta indica, Ficus racemosa, and Tinospora cordifolia are also included in the composition. One to two grams of the medicinal composition of 5 the invention are administered to a diabetic human subject three times a day before meals. The unique combination of components in the medicinal composition leads to a regeneration of the pancreas cells which then start producing insulin on their own. Since the composition restores normal pancreatic function, treatment can be discontinued after between about four and twelve months. A process for preparation of a dosage form for treatment of diabetes has not disclosed in the patent literature so far wherein Caesalpinia bonduc in general and its seed kernel powder in particular is used as active ingredient. The present invention describes industrially applicable oral dosage form convenient for the administration of the nut kernel of Caesalpinia bonduc to patients and a process for production of the said oral dosage form. DETAILED DESCRIPTION OF THE INVENTION Traditional knowledge of medicinal properties of paste of seed kernels of Caesalpinia bonduc have led attempts of researchers to extract the active principle so that medicinal properties can be applied commercially. However, no method of extraction of active principle in a liquid has succeeded so far because the dried extracts did not show the same medicinal properties as shown by the paste of seed kernels prepared by method described in Ayurveda. This is quite intriguing and held up commercial application of this plant for treatment of diseases. Ayurveda is a very exhaustive study of medicinal plants and except for modern methods of working with medicinally active principles in plants, like extraction of the active principle in pure and concentrated form, characterization, derivatization, synthesis of analogues etc. no one would expect that a simple way of using a medicinal plant, if feasible, would not have been known to Ayurveda. 6 In addition to that, in the context of the knowledge that although paste of kernel is effective in Ayurveda the dried contents of liquid extracts did not work, success achieved in getting efficacy of kernel powder of Caesalpinia in this invention came as a big unexpected surprise and is one of the main embodiments of this invention. Further, it must be mentioned here that in the context of medicinal plants, the form of the medicinal preparation is very specific. In the context of this peculiarity too, the knowledge that paste prepared from kernel is efficacious, does not automatically suggest that kernel powder shall also be efficacious. Such anticipations have never worked in Ayurveda. Had this been not so, when paste is effective, dried extracts would not have failed to show the same medicinal properties. Thus in this case at least, the prior knowledge that paste of the kernel has anti-diabetic property does not inherently suggest that kernel powder shall also be effective. Lack of its mention in Ayurveda and total absence of seed kernel powder as medicine for diabetes or diabetic disorders in market so far are further proofs of fact that anti-diabetic efficacy of seed kernel powder of Caesalpinia bonduc was never anticipated. This finding, i.e. efficacy of seed kernel powder against diabetes and diabetic disorders, for the first time opened possibilities of commercialization of medicinal properties of this plant. Developing this invention into a process of production was, however, further saddled with a series of further unanticipated problems typical to this product and solutions to them constitute further embodiments of this invention. One problem in using kernel as a powder for commercial production is to produce a powder itself from kernels for this purpose on a commercial scale, because removal of seed coat is one of the most difficult jobs. Known machines capable of removing seed coat do not work on these seeds because the seed 7 coat is fragile and produces fine and sharp pieces in any powdering machine, such pieces get mixed with the broken kernels / kernel powder producing a practically inseparable mixture. Parts of seed coat can not be allowed to be administered to a patient with kernel powder, in addition to sharpness of the fine pieces as a reason, partly because it is an indigestible matter and mainly because it contains oils and other ingredients which have unknown effects on the patient. Even manual cracking of the seeds is difficult by conventionally known techniques because the hard seed coat is slippery too and when hit by a hammer, the seed gets ejected from its place or gets badly smothered again leading to problem of mixing of fragmented kernel and pieces of seed coat. A further problem in mechanical bulk powdering is that the kernels are often infested with insects and pests and they can not be distinguished from outside before the seed coat is removed. Thus, any process of mass scale powdering of the seeds is saddled with the problem of being unable to avoid getting diseased kernels in to the product. Disease infested kernels give rise to yet another reason for which seeds can not be allowed to be broken while removing the seed coat or can not be handled or milled in a bulk making it essential to handle every seed independently on its own merits. At the most a seed can be allowed to be split into two big pieces, which can be easily hand picked and removed from the cracked pieces of seed coat. If any finer pieces are allowed to be produced from the seed kernels, such fine pieces arising from diseased kernels would get inseparably mixed with the bulk of separated seed kernel pieces and shall be impossible to be separated. Thus it is an embodiment of this invention that a process of preparation of the powder of the kernels should essentially involve separation of seed coat of individual seeds with seed kernel essentially intact or in such big pieces that any disease infested 8 kernel can be separately picked out and un-infested clean acceptable pieces of seed kernel be easily separated from the pieces of cracked seed coat. This invention also relates to invent a process to make it possible to separate seed coat from the kernel in a commercial production. One embodiment to make this possible is development of a block, preferably wooden, which has a depression in it made on one of its surfaces, usually in the top surface, which is deep enough to hold an individual seed, expose it to a hit of hammer, preferably a rubber or plastic hammer, made by a judicious force just enough to crack the seed coat but not to crush the seed and the depth of the depression being enough to hold the seed in its place and prevent its ejection after hammering. This basic design and process of removal of seed coat may be mechanized in a scale up, for example by having a block with multiple depressions receiving a hit from a mechanical device calibrated to reproduce the judicious hit given manually by a rubber or plastic hammer or the principle of cracking seed coat of individual seed without crushing the seed be replicated in some way by mechanical means. Other way, for example, to simulate the basic principle of cracking a seed coat individually is to shoot a seed against a stationary surface by a force judicious enough to achieve cracking of the seed coat without disintegrating the kernel to small pieces. In present invention, seeds are being cracked manually and uninfested kernels hand- picked up manually and collected in a heap for further processing. Freshly collected seeds are usually sun dried and then taken up for production of kernel separation and powdering the kernels. The accepted kernels are powdered, sifted and filled in capsules or made into tablets and the said tablets preferably coated to avoid bitter taste. Moisture content of the seed kernel powder at the time of filling a capsule was usually around 5% W/W. 9 Although the seed kernel powder is preferably filled alone with no other ingredients in a capsule, the practice may include to fill it with one or more of the other pharmaceutically active ingredients, excipients, taste modifying agents, flavour modifying agents, taste masking agents, taste modifying agents, a sweetening agent and the like; the said tablet is preferably coated to avoid the bitter taste; the said capsule preferably is a hard gelatin capsule. The capsule may also be made with various other alternative ingredients. The capsules and tablets may also be such as to provide a controlled release mechanism. This invention has for the first time made an oral dosage form available for antidiabetic application of medicinal properties of Caesalpinia bonduc, more particularly so for its extremely bitter kernel powder and is one of the embodiments of this invention. A capsule of the seed kernel powder of Caesalpinia bonduc has observed to be a dosage form found particularly convenient by patients for use as well as maintaining compliance. Most obvious alternative for a capsule is pressing the powder into a tablet, with additional ingredients if necessary, and coating the same in such a way that bitter taste is avoided during administration of the medicine; and this form is also covered in the scope of this invention. It has been noted that a dosage of one capsule one time a day with 500 mg of the kernel powder per capsule lowered blood sugar level from 200 mg to 135 mg in 20 days. The dosage required per day of the kernel powder per person will vary from person to person, usually from 50 mg to 1000 mg per day. It was seen that as compared to the fact that in conventional process of making a paste by rubbing against a grinding stone is repulsive even for the person making such a paste due to highly repulsive odour inducing a vomiting sensation too at times, method of this invention comprising extracting and handling the kernels up 10 40 powder making as well as filling in capsules or making a tablet is easily bearable in a production set up for people working on the process of production. The trial use of above described capsules of kernel powder of Caesalpinia in the diabetes affected persons have resulted in lowering of the blood sugar. The other benefit the patients obtained includes increase in general vigour and improvement in appetite. The dosage form was found to be very well accepted by the patients as reflected in good compliance in continuing the treatment. Described in the following are examples, which illustrate working of this invention without limiting the scope of this invention in any manner including a process of procuring the plant material, a process of removal of seed coat, a process and machine used for powdering the kernels or kernel pieces, a process of making an oral dosage form capable of masking the bitterness of the kernel powder, material of a capsule and the like, given in the example are for the purpose of illustration and any adaptation of equivalents normally obvious to the people skilled in use of medicinal plants for disease treatment, making pharmaceutical compositions and oral dosage forms are also included within the scope of this invention. Further, mention in singular is construed to cover its plural also, including all equivalent alternatives encompassed by that expression, unless the context does not permit so, viz: mention of "an other pharmaceutically active ingredient, an excipient, a taste modifying agent, a flavour modifying agent, a taste masking agent, a taste modifying agent, a sweetening agent and the like" shall include mention of one or more of, individually or in a mixture of, unless not compatible with the seed kernel powder, of all the known pharmaceutically active ingredients, excipients, taste modifying agents, flavour modifying agents, sweetening agents including high intensity sweeteners and any other ingredient that is used to formulate a more acceptable pharmaceutical composition. II EXAMPLE 1 The seed collected from the wild was dried in the sun. The seed coat was manually and carefully broken to take out the intact kernel. Each seed was individually cracked open by keeping it in a pit / depression of about 1.5 cm diameter made in to the center of a block of a size preferably of 2.5 cm height, 25 cm length and 15 cm width made preferably in wood, the pit being made on the top surface, the top surface measuring 25 cm length and 15 cm width. When seed is kept in this pit and hammered with a rubber hammer, the seed coat cracks open yielding an intact kernel. The separated kernels were then segregated from the seed coat pieces. The separated kernels were powdered in hammer mill and sifted to remove coarse particles. The powder was then filled in the hard gelatin capsule. Each capsule was filled with 500 mg of the powder. The results taken on the diabetic patients showed that the sugar level was dropped from 200 mg to 135 mg after shifting on this new drug in a period of 20 days. The patients felt improvement in general health. 12 A process of preparation of an oral dosage form, comprising seed kernel powder of Cesalpinia bonduc (L.) Roxb. as at least one ingredient, further comprising removing the seed coat from the seeds from essentially intact seed kernel without allowing them to get disintegrated in to finer pieces, removing the seed kernels from pieces of seed coat, rejecting insect infested and pest infested kernels, powdering the kernels and preparing a unit oral dosage form from them capable of avoiding bitter taste and repulsive flavour during oral administration. A process of claim 1 wherein: a. removing the seed coat from the seed is achieved preferably by cracking open the same by applying a judicious hit to a seed just enough to crack it open but not allowing to crush the kernel into pieces finer than one or two pieces from each and removing the cracked open seed coat by hand or by a mechanical device; the said judicious hit being applied, amongst one or more of a possible way to get the same effect, preferably by keeping the seed in a pit of a size enough to hold it and yet keep it accessible for receiving a hit and by hitting the same by a hammer which preferably is a rubber or plastic hammer further preferably manually by hand, or alternatively by mechanically simulating this process comprising hitting a seed in a block by a hammer or by shooting a seed on to a stationary surface by a force just enough to crack the seed coat without disintegrating the kernel into smaller pieces, and the like, b. if cracked open seed coat is not automatically removed, removing the cracked seed coat from the kernel individually by hand or by mechanical means, 13 c. inspecting each kernel individually and rejecting the kernels infested by insects and pests and collecting the clean kernels separately, d. powdering the kernels, e. subjecting the kernel powder to one or more of a process of preparing one or more of an oral dosage form, with or without a controlled release mechanism, comprising filling in a capsule, or pressing in to a tablet, and the like; wherein the said kernel powder may be used alone or with one or more of the other pharmaceutically active ingredients, excipients, taste modifying agents, flavour modifying agents, taste masking agents, taste modifying agents, a sweetening agent and the like; the said tablet is preferably coated to avoid the bitter taste; the said capsule preferably is a hard gelatin capsule. 3. A process of claim 2 wherein the said capsule is a hard gelatin capsule containing kernel powder, each capsule containing 50 mg to 1000 mg preferably 500 mg of the kernel powder. 4. A process of claim 3 comprising steps of: a. placing a seed in to a shallow pit of about 1.5 cm. diameter made in to the center of a block of a size preferably of 2.5 cm height, 25 cm length and 15 cm width made preferably in wood, the pit being made on the top surface measuring 25 cm length and 15 cm width, b. hammering the seed judiciously to achieve cracking opening of the seed coat leaving the kernel intact, the said hammer preferably being made from rubber or plastic, c. segregating the seed kernels from the separated seed coat pieces, 14 d. picking out and rejecting the seed kernels affected by insects and pests, e. powdering the seed kernels in a hammer mill and sifting the powder, and f. filling the fine powder in a capsule in a per capsule quantity of 50mg to 1000 mg, preferably with 500 mg and the capsule being preferably a hard gelatin capsule. 5. An oral dosage form, with or without a controlled release mechanism, containing seed kernel powder of Cesalpinia bonduc (L.) Roxb. as at least one ingredient with or without one or more of an other pharmaceutical^ active ingredient, an excipient, a taste modifying agent, a flavour modifying agent, a taste masking agent, a taste mofifying agent, a sweetening agent and the like. 6. A product of claim 5 wherein the said dosage form is a capsule or a tablet; the said capsule being preferably a hard gelatin capsule, the said tablet being preferably a coated tablet capable to avoid bitter taste and offensive flavour during oral administration. 7. A product of claim 6 containing kernel powder 50 mg to 1000 mg, preferably 500 mg. 8. An oral dosage form including a capsule prepared by process of claim 1, or claim 2 or claim 3 or claim 4. 9. A product of claim 7 prepared by any one of a process of claim 1, or claim 2 or claim 3 or claim 4. 15 10. A process of administering an oral dosage form of any one of the claim 1, to claim 9 for treatment or prevention of diabetes and diabetic disorders in mammals in general and in a human being in particular. Dated this 25th day of October, 2005. FOR DIXIT SHAMKANT PRABHAKAR and KANK KISHOR LAXMAN By their Agent (VASANT ANANTRAO SAVANGIKAR) KRISHNA &SAURASTRI 16 ABSTARCT An oral dosage form, including a capsule, and a process of preparing the same from seed kernel powder of Cesalpinia bonducjl.) Roxb. has been described for treatment of diabetes and diabetic disorders. The process includes specialized device for removing seed coat from intact seed kernels, rejecting the kernels affected by insects and pets, powdering them and preparing an oral dosage form from the seed kernel powder. 17

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1342-MUM-2005-ABSTRACT(GRANTED)-(13-3-2009).pdf

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1342-MUM-2005-DESCRIPTION(GRANTED)-(13-3-2009).pdf

1342-MUM-2005-DESCRIPTION(PROVISIONAL)-(25-10-2005).pdf

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1342-MUM-2005-FORM 2(PROVISIONAL)-(25-10-2005).pdf

1342-MUM-2005-FORM 2(TITLE PAGE)-(COMPLETE)-(17-10-2006).pdf

1342-MUM-2005-FORM 2(TITLE PAGE)-(GRANTED)-(13-3-2009).pdf

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1342-MUM-2005-SPECIFICATION(AMENDED)-(21-5-2008).pdf