Claims for Patent: 7,569,236

Summary for Patent: 7,569,236

Title:	Sustained-release microgranules containing gingko biloba extract and the process for manufacturing these
Abstract:	The subject of the present invention is a new stable herbal drug formulation in the form of sustained-release microgranules containing Gingko Biloba extract as well as the process for preparing it.
Inventor(s):	Marechal; Dominique (Laval, CA), Yang; Wei-hong (Shanghai, CN), Hu; Yu-zhang (Shanghai, CN)
Assignee:	Ethypharm (Houdan, FR)
Application Number:	10/574,923
Patent Claims:	1. Sustained release microgranules containing a Ginkgo biloba extract, comprising: a neutral core coated with a layer, said layer containing Ginkgo biloba extract with at least one pharmaceutically acceptable excipient; an intermediate water-repellent layer, coating said core, comprising a thermoplastic excipient selected from the group consisting of partially hydrogenated oils, beeswax, carnauba wax, paraffin waxes, silicone waxes, C12-C18 fatty alcohols and fatty acids, solid, semi-synthetic glycerides, glycerol monoesters, diesters or triesters, polyoxyethylene glycols and glycosylated polyoxyethylenated glycerides, monostearate glycerides and mixtures thereof; and an outer polymeric layer which sustains the release of said extract from the active core; wherein the release of total flavone glycosides having the following profile of dissolution rates measured at 37.0.degree. C..+-.0.5.degree. C., with a Dissolution Test Apparatus I (Basket method at 100 rpm, 900 mL of purified water UV Detection: 272 nm): TABLE-US-00010 T (h) DISSOLUTION (w/w) 0.5 hour .sup. .ltoreq.45% 2 hours <75% 8 hours >60%. 2. Sustained release microgranules according to claim 1, wherein the profile is as follows: TABLE-US-00011 T (h) Dissolution (w/w) 0.5 hour .sup. 5-45% 2 hours 30-70% 8 hours >60%. 3. Sustained release microgranules according to claim 1, wherein the neutral core consists of a substance chosen from sugar, starch, mannitol, sorbitol, xylitol, cellulose, talc and mixtures thereof. 4. Sustained release microgranules according to claim 3, wherein the neutral core consists of a starch/sucrose core in 80/20 mass ratios. 5. Sustained release microgranules according to claim 1, wherein the Ginkgo biloba extract contains up to 40% by weight of flavonoids, and up to 10% by weight of terpenes. 6. Sustained release microgranules according to claim 5, wherein the Ginkgo biloba extract preferably contains up to 24% by weight of flavonoids, and up to 6% by weight of terpenes. 7. Sustained release microgranules according to claim 1, wherein the layer containing the Ginkgo biloba extract contains at least one pharmaceutically acceptable excipient, selected from the group comprising a binder, an antistatic agent or a lubricant. 8. Sustained release microgranules according to claim 7, wherein the binder is selected from the group consisting of cellulosic polymers, acrylic polymers, polyacrylate, povidones, copovidones, polyvinylalcohols, shellac, alginic acid, sodium alginate, starch, pregelatinized starch, sucrose and its derivatives, guar gum, polyethylene glycol. 9. Sustained release microgranules according to claim 8, wherein the binder is used in proportions of at most about 50% by weight of Ginkgo biloba extract. 10. Sustained release microgranules according to claim 7, wherein the antistatic agent, which can be used as flow aid, is selected from the group consisting of micronised or non micronised talc, fumed silica, colloidal silica, precipitated silica and mixtures thereof. 11. Sustained release microgranules according to claim 10, wherein the antistatic agent is used in proportions of at most 5% by weight relative to the weight of said granules of Ginkgo biloba. 12. Sustained release microgranules according to claim 7, wherein the lubricant is selected from the group consisting of magnesium stearate, stearic acid, sodium stearyl fumarate, micronised polyoxyethyleneglycol, leukine, sodium benzoate and mixtures thereof. 13. Sustained release microgranules according to claim 1, wherein the outer polymeric layer contains at least one coating agent selected from the group consisting of cellulosic polymers, acrylic polymers, shellac and mixtures thereof. 14. Sustained release microgranules according to claim 13, wherein the cellulosic polymer is selected among ethylcellulose, hydroxypropylcellulose and/or hydroxypropylmethylcellulose. 15. Sustained release microgranules according to claim 13, wherein the acrylic polymer is selected from insoluble acrylate ammonio-methacrylate copolymer, polyacrylate, or methacrylic copolymers, and combinations thereof. 16. Sustained release microgranules according to claim 13, wherein the outer polymeric layer additionally contains a plasticizer, a surfactant, an antistatic agent and/or a lubricant. 17. Sustained release microgranules according to claim 16, wherein the plasticizer is selected in the group consisting of dibutyl sebacate, triacetine, triethylacetate, triethylcitrate, ethylphtalate, or mixtures thereof. 18. Sustained release microgranules according to claim 17, wherein the plasticizer is used in proportions of at most about 30% by weight of the coating agents. 19. Sustained release microgranules according to claim 16, wherein the antistatic agent is selected from the group comprising micronised or non micronised talc, fumed silica, colloidal silica, precipitated silica and mixtures thereof. 20. Sustained release microgranules according to claim 16, wherein the antistatic agent is used in proportions of at most about 10%, by weight. 21. Sustained release microgranules according to claim 20, wherein the thermoplastic excipient comprised in the water-repellent layer is monostearate glyceride. 22. Process for the preparation of sustained release microgranules according to claim 1, comprising the successive steps consisting of: applying over a neutral core, a layer comprising Gingko Biloba extract, and at least one pharmaceutical excipient; coating said core with an intermediate layer over the thus obtained granules by spraying thereon a suspension, or a solution comprising a thermoplastic excipient coating the thus coated granules with an outer polymeric layer by spraying a suspension, a dispersion or a solution of a sustained-release coating composition, drying the thus obtained coated granules. 23. Process for the preparation of sustained release microgranules according to claim 22, wherein the layer is applied over the neutral cores by spraying a coating alcoholic solution containing the Gingko Biloba extracts and the excipient. 24. Process for the preparation of sustained release microgranules according to claim 23, wherein the alcoholic or aqueous alcoholic solution contains isopropylic alcohol. 25. Process for the preparation of sustained release microgranules according to claim 23, wherein the layer applied over the neutral cores is a 10% w/w binding solution of shellac dissolved in isopropyl alcohol. 26. Process for the preparation of sustained release microgranules according to claim 22, wherein the outer coating layer is a water dispersion of ethylcellulose at 16% w/w containing 25% w/w of dibutyl sebacate versus dry polymer. 27. Process for the preparation of sustained release microgranules according to claim 2, comprising the successive steps consisting of: applying over a neutral core, a layer comprising Gingko Biloba extract, and at least one pharmaceutical excipient; coating said core with an intermediate layer over the thus obtained granules by spraying thereon a suspension, or a solution comprising a thermoplastic excipient coating the thus coated granules with an outer polymeric layer by spraying a suspension, a dispersion or a solution of a sustained-release coating composition, drying the thus obtained coated granules.

Details for Patent 7,569,236

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Partner Therapeutics, Inc.	LEUKINE	sargramostim	For Injection	103362	03/05/1991		2023-10-10
Partner Therapeutics, Inc.	LEUKINE	sargramostim	Injection	103362	03/05/1991		2023-10-10