BOSWELLIN COMPOSITIONS ENHANCED WITH 3-beta-ACETYL-11-KETO-beta-BOSWELLIC ACID ("AKBA"), INDUSTRIAL MANUFACTURE AND THEIR USES 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
WO03077860 A2 2003-09-25 [WO200377860]WO03077860 A3 2004-04-08 [WO200377860] / 2003-09-252004-04-08
申请号/申请日
2003WO-US07733 / 2003-03-12
发明人
SELIGSON ALLEN L;TERRY RONALD C;ALEXANDER DANIEL;SOVAK MILOS;
申请人
BIOPHYSICA;
主分类号
IPC分类号
A61K-031/19A61K-031/225A61K-036/324C07C-067/02
摘要
(WO200377860) The biological activity of naturally occurring boswellic acids in specific plant extracts is enhanced by their peracetylation, preferably followed by silica gel treatment, or by per-acetylation and mild oxidation to increase the ratio of 3-beta-acetyl-11-keto-beta-boswellic acid to beta-boswellic acid, 3-beta-acetyl-beta-boswellic acid and 11-keto-beta-boswellic acid.  The enriched compositions compared to the commercial extracts have enhanced biological activity toward a variety of proliferative and/or inflammatory afflictions in mammalian hosts and demonstrate synergism with other phytochemicals.
机翻摘要
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地址
代理人
代理机构
;
优先权号
2002US-60364299 2002-03-13
主权利要求
(WO200377860) 1. We Claim: 1. A therapeutic composition prepared by the method comprising: peracetylating a Boswellia serrata pentacyclic terpene acidic fraction extract to provide a peracetylated product; and optionally oxidizing said peracetylated product with a mild oxidizing agent, to provide a product having a maj or portion by weight of 3 - β -acetoxy - 11 -keto- β -boswellic acid. 2. A composition according to claim 1 , wherein said oxidizing agent is a peroxide. 3. A composition according to Claim 1, wherein said peroxide is tert-butyl hydroperoxide. 4. A composition according to Claim 1 , wherein said oxidizing agent is a metal oxide. 5. A composition according to Claim 4, wherein said metal oxide is chromium trioxide. 6. A composition according to Claim 4, wherein said oxidizing agent is an active halogen. 7. A composition according to Claim 6, wherein said active halogen is an N-substituted halogen. 8. A composition according to Claim 7, wherein said N-substituted halogen is N-bromo succinimide. 9. A method of treating a mammalian host for neoplasia or inflammation, said method comprising: administering to said mammalian host a therapeutically effective amount of a composition or its physiologically acceptable salts, prepared according to the method comprising peracetylating a Boswellia serrata pentacyclic terpene acidic fraction extract to provide a peracetylated product having a ratio of AKBA to the other boswellic acid components in boswellin increased compared to said acidic fraction. 10. A method for treating a mammalian patient for neoplasia, or inflammation, said method comprising: administering to said mammalian host a therapeutically effective amount of a composition according to Claim 1 or its physiologically acceptable salts. 11. A method for enhancing the therapeutic activity of the pentacyclic acidic fraction from Boswellia serrata, said method comprising: peracetylating said acidic fraction with an acetylating agent to provide a peracetylated product; and optionally oxidizing said peracetylated product with a mild oxidizing agent, whereby producing AKBA having enhanced therapeutic activity compared to said pentacyclic acidic fraction. 12. A method according to Claim 11 , wherein said mild oxidant is a peroxide. 13. A method according to Claim 11, wherein said mild oxidant is a metal oxide 14. A method according to Claim 11 , wherein said mild oxidant is an active halogen. 15. A therapeutic composition, comprising: a mixture of boswellic acids having AKBA in an amount greater than about 20% of the total boswellic acids by weight; a solubilizing agent; and a physiologically compatible carrier. 16. The composition of Claim 15, wherein said AKBA is present in an amount greater than about 50% of the total boswellic acids in said mixture. 17. The composition of Claim 15, wherein said AKBA is present in an amount greater than about 85% of the total boswellic acids in said mixture. 18. The composition of Claim 15, wherein said AKBA is increased by a factor of at least about 90% compared to an unenhanced boswellin. 19. The composition of Claim 15, wherein said AKBA is present in an amount of about 100% of the total boswellic acids in said mixture. 20. A tablet comprising the composition of Claim 15 and a binder. 21. A capsule comprising the composition of Claim 15. 22. A solution comprising the composition of Claim 15. 23. A method for treating a mammal suspected of having neoplasia or inflammation, comprising the step of administering to said mammal a therapeutically active amount of a composition of boswellic acids having AKBA or physiologically acceptable salts thereof in an amount greater than about 20% by weight of the total boswellic acids. 24. A method for decreasing production of products of arachidonic acid in a mammal, comprising the step of administering to said mammal a therapeutically effective amount of the composition of Claim 15 or one or more of its physiologically acceptable salt. 25. A method for treating inflammation in a mammal, comprising the step of administering to said mammal a therapeutically effective amount of the composition of Claim 15 or its physiologically acceptable salts. 26. A method for treating neoplasia in a mammal, comprising the step of administering to said mammal a therapeutically effective amount of the composition of Claim 15 or its physiologically acceptable salts. 27. A therapeutic composition, comprising: a mixture of boswellic acids having BA in an amount less than about 40% of the total boswellic acids by weight and having AKBA in an amount greater than about 20% by weight; and a physiologically compatible carrier. 28. A therapeutic composition, comprising: a mixture of boswellic acids having ABA in an amount less than about 25% of the total boswellic acids by weight and having AKBA in an amount greater than about 20% by weight; and a physiologically compatible carrier. 29. A therapeutic composition, comprising: a mixture of boswellic acids having KBA in an amount less than about 15% of the total boswellic acids by weight and having AKBA in an amount greater than about 20% by weight; and a physiologically compatible carrier. 30. A therapeutic composition, comprising: a mixture of boswellic acids; and one or more compounds selected from the group consisting of resveratrol, resveratrolosides, genistein, licochalcone A and baicalin; wherein the combination of said compounds produces an effect greater than the sum of the effects of each compound individually. 31. The composition of Claim 30, wherein said effect is anti-neoplastic and/or anti- inflammatory. 32. A method for treating neoplasia in a mammal, comprising the step of administering to said mammal a therapeutically effective amount of the composition of Claim 27 or at least one of its physiologically acceptable salts. 33. A method for treating neoplasia in a mammal, comprising the step of administering to said mammal a therapeutically effective amount of the composition of Claim 30 or at least one of its physiologically acceptable salts. 34. The method of claim 32, wherein said neoplasia is selected from the group consisting of lymphoblastic leukemia, prostate cancer, lung cancer, melanoma, and breast cancer. 35. A method for inhibiting the production of tumor necrosis factor alpha (TNF- α), comprising exposing to a TNF-α-producing cell, a pharmacologically effective amount of a boswellic acid. 36. The method of claim 35, wherein said boswellic acid is AKBA-enriched boswellin. 37. A method for treating an mammal for a condition characterized by abnormally increased production of TNF-α, comprising administering to said mammal, a therapeutically effective amount of a boswellic acid composition having a concentration of AKBA greater than that present in a pentacyclic acidic fraction of boswellin. 38. A method for treating an animal suffering from neoplasia, comprising administering to said mammal, an amount of AKBA-enriched boswellin sufficient to produce a therapeutic effect in said mammal. 39. The method of claim 38, wherein said therapeutic effect is a decrease in tumor size. 40. The method of claim 38, wherein said therapeutic effect is increase in survival time. 41. The composition of claim 27, wherein said boswellic acids include at least one salt that is solubilized in cyclodextrin. 42. The composition of claim 30, wherein said boswellic acids include at least one salt that is solubilized in cyclodextrin. 43. A method for commercial production of boswellic acids, comprising: (a) dissolving a crude extract of Boswellia serrata in an organic solvent forming an organic extract; (b) treating said organic extract with a base and water forming an aqueous layer; (c) acidifying said aqueous layer forming an acidified aqueous extract; (d) adding a filtration agent and magnesium sulfate to said acidified aqueous extract; and (e) filtering said extract produced by step (d). 44. A method for commercial peracetylation of a boswellic acid extract, comprising: (a) adding a pyridine and an acetic anhydride to a commercial extract of boswellic acids forming a peracetylated boswellic acid fraction in a solvent; (b) extracting said peracetylated boswellic acid fraction with an inorganic acid and a salt; (c) adding a filtration agent and magnesium sulfate to said peracetylated boswellic acid fraction; (d) exchanging said solvent with acetic acid and water, forming a precipitate; and (d) collecting said precipitate. 45. A method for commercial oxidation of boswellic acids, comprising: (a) adding calcium carbonate to a peracetylated boswellic acid fraction; (b) adding methyl cyclohexene to said preparation obtained in step (a); (c) adding N-bromosuccinimide to the preparation obtained in step (b); and (d) irradiating said preparation obtained in step (c). 46. A method for forming a sodium salt of peracetylated boswellic acid, comprising: (a) adding ethyl acetate and ethanol to a preparation of peracetylated boswellic acid; and (b) adding sodium hydroxide to the preparation obtained in step (a) until a pH of 8 to 9 is reached and a sodium salt of said peracetylated boswellin forms. 47. A method for improving the solubility of boswellic acids, comprising (a) adding (2-hydroxypropyl)-gamma-cyclodextrin to peracetylated boswellin forming a mixture ; (b) finely dividing the mixture obtained in step (a); and (c) adding a solution of saturated sodium bicarbonate in water to said finely divided mixture until said mixture dissolves. 48. A composition, comprising: a mixture of boswellic acids enriched in AKBA compared to an pentacyclic terpene acidic fraction of boswellic acids; at least one other phytochemical selected from the group consisting of resveratrol, resveratrolosides, genistein, licochalcone A and baicalin; and a physiologically compatible lipophilic carrier.
法律状态
(WO200377860) LEGAL DETAILS FOR WO03077860  Actual or expected expiration date=2005-09-13    Legal state=DEAD    Status=LAPSED     Event publication date=2003-03-12  Event code=WO/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=WO WOUS0307733  Application date=2003-03-12  Standardized application number=2003WO-US07733     Event publication date=2003-09-25  Event code=WO/A2  Event type=Examination events  International application published without international search report  Publication country=WO  Publication number=WO03077860  Publication stage Code=A2  Publication date=2003-09-25  Standardized publication number=WO200377860     Event publication date=2003-09-25  Event code=WO/AL  Event indicator=Pos  Event type=Designated states  Designated countries for regional patents GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG    Event publication date=2003-09-25  Event code=WO/AK  Event indicator=Pos  Event type=Designated states  Designated states AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PH PL PT RO RU SC SD SE SG SK SL TJ TM TN TR TT TZ UA UG UZ VC VN YU ZA ZM ZW    Event publication date=2004-04-08  Event code=WO/A3  Event indicator=Pos  Event type=Examination events  Later publication of ISR with revised front page  Publication country=WO  Publication number=WO03077860  Publication stage Code=A3  Publication date=2004-04-08  Standardized publication number=WO200377860     Event publication date=2005-09-13  Event code=WO/EETL  Event type=Event indicating Not In Force  PCT Application validity period expired. LEGAL DETAILS FOR DESIGNATED STATE AU2003220240  Actual or expected expiration date=2004-12-02    Legal state=DEAD    Status=LAPSED   Corresponding cc:  Designated or member state=AU Corresponding appl: AU2003220240  Application date in the designated or member state=2003-03-12   Application number in the designated or member state=2003AU-0220240 Corresponding cc:  Designated or member state=AU Corresponding pat: AU2003220240  Publication stage code in the designated or member state=A1  Publication date in the designated or member state=2003-09-29   Publication number in the designated or member state=AU2003220240    Event publication date=2004-12-02  Event code=AU/STCHG  Patent Status changed by the national office Corresponding cc:  Designated or member state=AU  LEGAL DETAILS FOR DESIGNATED STATE JP  Actual or expected expiration date=2006-06-22    Legal state=DEAD    Status=LAPSED   Corresponding cc:  Designated or member state=JP     Event publication date=2006-06-22  Event code=WO/NENP  Event type=Event indicating Not In Force  Non-entry into the national phase in: Corresponding cc:  Designated or member state=JP     Event publication date=2006-06-22  Event code=WO/WWW  Event indicator=Neg  Event type=Event indicating Not In Force  Wipo information: withdrawn in national office Corresponding cc:  Designated or member state=JP  LEGAL DETAILS FOR DESIGNATED STATE SE0302923  Actual or expected expiration date=2005-11-08    Legal state=DEAD    Status=LAPSED   Corresponding cc:  Designated or member state=SE Corresponding appl: SE0302923  Application date in the designated or member state=2003-11-06   Application number in the designated or member state=2003SE-0002923 Corresponding cc:  Designated or member state=SE Corresponding pat: SE0302923  Publication stage code in the designated or member state=D0  Publication date in the designated or member state=2003-11-06   Publication number in the designated or member state=SE200302923    Event publication date=2003-11-06  Event code=WO/WWE  Event indicator=Pos  Event type=Entry into national phase  Wipo information: entry into national phase Corresponding cc:  Designated or member state=SE     Event publication date=2003-12-22  Event code=WO/WWP  Event indicator=Pos  Event type=Examination events  Wipo information: published in national office Corresponding cc:  Designated or member state=SE     Event publication date=2005-11-08  Event code=SE/STCHG  Patent Status changed by the national office Corresponding cc:  Designated or member state=SE
专利类型码
A2A3
国别省市代码
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