Biomimetic of fruit extract for amelioration of inflammation
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-031/497
A61K-031/44
출원번호
UP-0660283
(2005-08-11)
등록번호
US-7655659
(2010-03-31)
국제출원번호
PCT/US2005/028630
(2005-08-11)
§371/§102 date
20070215
(20070215)
국제공개번호
WO06/023377
(2006-03-02)
발명자
/ 주소
Yarosh, Daniel B.
Brown, David A.
Canning, Matthew T.
출원인 / 주소
Applied Genetics Incorporated Dermatics
인용정보
피인용 횟수 :
0인용 특허 :
5
초록▼
Compositions and methods are provided for reversing and/or inhibiting inflammation, e.g., by inhibiting prostaglandin and/or COX-2 production, using one or more indolequinazoline alkaloids, preferably in combination with butylated hydroxytoluene. The preferred indolequinazoline alkaloids are rutaeca
Compositions and methods are provided for reversing and/or inhibiting inflammation, e.g., by inhibiting prostaglandin and/or COX-2 production, using one or more indolequinazoline alkaloids, preferably in combination with butylated hydroxytoluene. The preferred indolequinazoline alkaloids are rutaecarpine, evodiamine, and dehydroevodiamine, which are naturally found in unpurified form in the traditional Chinese medicine Wu Chu Yu made from the fruit of the herb, Evodia rutaecarpa.
대표청구항▼
What is claimed is: 1. A composition comprising: a. one or more indolequinazoline alkaloids; b. butylated hydroxytoluene; and c. one or more solvents and/or one or more carriers; wherein: (i) the combined concentrations of the one or more indolequinazoline alkaloids in the composition is at least
What is claimed is: 1. A composition comprising: a. one or more indolequinazoline alkaloids; b. butylated hydroxytoluene; and c. one or more solvents and/or one or more carriers; wherein: (i) the combined concentrations of the one or more indolequinazoline alkaloids in the composition is at least 0.02 μg/ml and the concentration of butylated hydroxytoluene is at least 0.01 mg/ml; and/or (ii) the sum of the dry weights of (a) and (b) in the composition is at least 10 percent of the weight of total solids in the composition; and/or (iii) the quotient of the light absorption of the composition at 550 nanometers divided by its absorption at 270 nanometers is less than or equal to 0.01; and/or (iv) the quotient of the light absorption of the composition at 450 nanometers divided by its absorption at 400 nanometers is less than or equal to 0.1. 2. The composition of claim 1 wherein the sum of the dry weights of(a) and (b) in the composition is at least 90 weight percent of the total solids in the composition. 3. The composition of claim 1 wherein the dry weight of (b) in the composition is at least 50 weight percent of the total solids in the composition. 4. The composition of claim 1 wherein the one or more solvents and/or one or more carriers comprises butylene glycol. 5. A composition comprising: a. one or more indolequinazoline alkaloids; and b. butylene glycol. 6. The composition of claim 5 further comprising butylated hydroxytoluene. 7. The composition of claim 1, 5, or 6 wherein: (i) the combined concentrations of the one or more indolequinazoline alkaloids in the composition is approximately 400-600 μg/ml; and/or (ii) the one or more indolequinazoline alkaloids are individually selected from the group consisting of rutaecarpine, evodiamine, dehydroevodiamine, and their salts; and/or (iii) the composition further comprises evodine; and/or (iv) the composition further comprises one or more agents which inhibit the production of prostaglandins; and/or (v) the composition further comprises one or more agents which have the potential to stimulate the production of prostaglandins; and/or (vi) the combined concentrations of the one or more indolequinazoline alkaloids in the composition are effective to at least partially reverse and/or at least partially inhibit inflammation; and/or (vii) the composition is in the form of an emulsion; and/or (viii) the composition is suitable for application to mammalian skin; and/or (ix) the composition is suitable for application to human skin. 8. The composition of claim 1 or 5 wherein: (i) the concentration of butylated hydroxytoluene is at least 0.05 mg/ml; and/or (ii) the concentration of butylated hydroxytoluene is 4-6 mg/ml and the combined concentrations of the one or more indolequinazoline alkaloids in the composition is approximately 400-600 μg/ml; and/or (iii) the combined concentrations of the one or more indolequinazoline alkaloids and the butylated hydroxytoluene in the combination are effective to at least partially reverse and/or at least partially inhibit inflammation. 9. A method for at least partially reversing and/or at least partially inhibiting skin inflammation of a mammal comprising applying to the skin of a mammal in need of such a reversal and/or inhibition a composition comprising (a) one or more indolequinazoline alkaloids having a purity greater than or equal to 50% when used to formulate the composition; and (b) butylated hydroxytoluene. 10. The method of claim 9 wherein the one or more indolequinazoline alkaloids has a purity greater than or equal to 90% when used to formulate the composition. 11. A method for at least partially reversing and/or at least partially inhibiting skin inflammation of a mammal comprising applying to the skin of a mammal in need of such a reversal and/or inhibition a composition comprising: a. one or more indolequinazoline alkaloids; and b. butylated hydroxytoluene; wherein the anti-inflammatory activity of the composition when tested using a methyl nicotinate induced erythema on human skin is substantially the same or greater than the anti-inflammatory activity of a composition which consists of butylene glycol in which is dissolved the same percentage weights by volume of the one or more indolequinazoline alkaloids and the butylated hydroxytoluene in the composition. 12. The method of claim 9 or 10 wherein: (i) the composition comprises butylene glycol; and/or (ii) the combined concentrations of the one or more indolequinazoline alkaloids in the composition is approximately 400-600 μg/ml; and/or (iii) the one or more indolequinazoline alkaloids are individually selected from the group consisting of rutaecarpine, evodiamine, dehydroevodiamine, and their salts; and/or (iv) the concentration of butylated hydroxytoluene in the composition is at least 0.05 mg/ml; and/or (v) the concentration of butylated hydroxytoluene in the composition is 4-6 mg/ml and the combined concentrations of the one or more indolequinazoline alkaloids in the composition is approximately 400-600 μg/ml; and/or (vi) the composition further comprises evodine; and/or (vii) the composition further comprises one or more agents which inhibit the production of prostaglandins; and/or (viii) the composition further comprises one or more agents which have the potential to stimulate the production of prostaglandins; and/or (ix) the composition is in the form of an emulsion; and/or (x) the skin is human skin. 13. A method for at least partially inhibiting the activity of cyclo-oxygenase-2 comprising administering to mammalian skin in need of such inhibition a composition comprising butylated hydroxytoluene, or tricyclo(3,3,1,1(3,7)-decane-1-carboxylic acid ethyl ester, or a combination of butylated hydroxytoluene and tricyclo(3,3,1,1(3,7)-decane-1-carboxylic acid ethyl ester, wherein the concentration of butylated hydroxytoluene, or tricyclo(3,3,1,1(3,7)-decane-1-carboxylic acid ethyl ester, or the combination of butylated hydroxytoluene and tricyclo(3,3,1,1(3,7)-decane-1-carboxylic acid ethyl ester in the composition is effective in at least partially inhibiting the activity of cyclo-oxygenase-2. 14. The method of claim 13 wherein: (i) the composition comprises butylene glycol; and/or (ii) the composition is in the form of an emulsion. 15. A method for inducing the skin of a mammal to produce nitric oxide comprising administering a composition comprising an effective amount of methyl nicotinate to the skin of a mammal which exhibits symptoms of impaired circulation. 16. The method of claim 15 wherein: (i) the skin exhibits erythromelalgia; or (ii) the skin exhibits Reynaud's syndrome. 17. A method for preparing a composition which can be used in a formulation which is to be applied to mammalian skin comprising: a. providing a first component comprising an indolequinazoline alkaloid; b. providing a second component comprising butylated hydroxytoluene; c. providing a carrier and/or a solvent suitable for application to mammalian skin; and d. using the first component, the second component, and the carrier and/or solvent to prepare the composition; wherein the purity of the indolequinazoline alkaloid in the first component is greater than or equal to 50 percent. 18. A method for preparing a formulation for application to mammalian skin comprising: a. providing a first component comprising an indolequinazoline alkaloid; b. providing a second component comprising butylated hydroxytoluene; c. providing a carrier and/or a solvent suitable for application to mammalian skin; and d. using the first component, the second component, and the carrier and/or solvent to prepare the formulation; wherein the purity of the indolequinazoline alkaloid in the first component is greater than or equal to 50 percent. 19. The method of claim 17 or 18 wherein: (i) the purity of the indolequinazoline alkaloid in the first component is greater than or equal to 90 percent; and/or (ii) the indolequinazoline alkaloid is selected from the group consisting of rutaecarpine, evodiamine, dehydroevodiamine, and their salts; and/or (iii) the carrier and/or solvent comprises butylene glycol.
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