RU98100111A - ACTIVE OSTEOGENESIS PHARMACEUTICAL COMPOSITION - Google Patents

Claims (1)

1. A pharmaceutical composition comprising a non-peptide osteogenesis activating substance and a biodegradable polymer.  2. The pharmaceutical composition according to claim 1, which further comprises phosphoric acid or its salt.  3. The pharmaceutical composition according to claim 1, where the non-peptide osteogenic activating substance is a non-steroid.  4. The pharmaceutical composition according to claim 1, used for local administration.  5. The pharmaceutical composition according to claim 1, used to activate the healing of bone fractures.  6. The pharmaceutical composition according to claim 1, which is a drug with a slow release. 7. The pharmaceutical composition according to claim 1, where the non-peptide osteogenic activating substance is a compound represented by formula I

where ring A is an optionally substituted benzene ring; R represents a hydrogen atom or an optionally substituted hydrocarbon group; B is an optionally esterified or amidated carboxyl group; X represents —CH (OH) - or —CO—; k represents 0 or 1; and k 'represents 0, 1 or 2, or a salt thereof. 8. The pharmaceutical composition according to claim 7, wherein ring A is a benzene ring which may be substituted with 1 or 2 substituents selected from the group consisting of: halogen, C _1-10 alkyl, C _1-10 alkoxy, - O- (CH ₂ ) _n —O—, where n is 1-3, and C _1-10 -alkylthio. 9. The pharmaceutical composition of claim 7, wherein B is —CON (R ₁ ) (R ₂ ), where R ₁ and R ₂ independently represent a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted 5-7 membered heterocyclic group . 10. The pharmaceutical composition according to claim 9, where R ₁ represents a hydrogen atom or a C _1-10 alkyl group and R ₃ represents (i) a phenyl or phenyl-C _1-3 alkyl group, which may be substituted by halogen, C _1-6 alkoxy, mono or di-C _1-6 alkoxyphosphoryl, mono or di C _1-6 alkoxyphosphoryl C _1-3 alkyl

where p is 2 to 4, or C _1-6 alkoxycarbonyl, or (ii) a 5- or 6-membered heterocyclic group containing 1 or 2 nitrogen atoms or 1 nitrogen atom and 1 sulfur atom, which may be substituted by phenyl. 11. The pharmaceutical composition according to claim 7, where R represents a hydrogen atom, a C _1-6 alkyl group or a phenyl group.  12. The pharmaceutical composition according to claim 7, where k represents 1 and k 'represents 0. 13. The pharmaceutical composition according to claim 1, where the non-peptide osteogenesis activating substance is an optically active compound represented by the formula

where R ₃ represents a lower alkyl group; and R ₄ and R ₅ independently represent a lower alkyl group or are linked together to form a lower alkylene group. 14. The pharmaceutical composition according to claim 13, wherein R ₃ , R ₄ and R ₅ independently represent a C ₁₆ alkyl group.  15. The pharmaceutical composition according to claim 1, wherein the compound is (2R, 4S) - (-) - N- [4- (diethoxyphosphorylmethyl) phenyl] -1,2,4,5-tetrahydro-4-methyl-7, 8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxamide.  16. The pharmaceutical composition according to claim 1, where the weight ratio of biodegradable polymer to non-peptide osteogenesis of the activating substance is approximately 1-100-fold.  17. The pharmaceutical composition according to claim 1, containing (2R, 4S) - (-) - N- [4- (diethoxyphosphorylmethyl) phenyl] -1, 2, 4, 5-tetrahydro-4-methyl-7,8-methylenedioxy -5-oxo-3-benzothiepin-2-carboxamide and a biodegradable polymer.  18. The pharmaceutical composition according to p. 17, which further comprises phosphoric acid or its salt.  19. The pharmaceutical composition according to claim 18, where the phosphoric acid or its salt is sodium phosphate. 20. The pharmaceutical composition according to claim 17, where the relative content of (2R, 4S) - (-) - N- [4- (diethoxyphosphorylmethyl) phenyl] -1,2,4,5-tetrahydro-4-methyl-7.8 -methylenedioxy-5-oxo-3-benzothiepin-2-carboxamide per biodegradable polymer is approximately 5-30 wt.% and the relative content of sodium phosphate based on (2R, 4S) - (-) - N- [4- (diethoxyphosphorylmethyl) phenyl] -1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxamide and a biodegradable polymer is approximately 0.1 -20 wt.%
21. The pharmaceutical composition according to claim 17, wherein the biodegradable polymer is a copolymer of lactic and glycolic acids.  22. The pharmaceutical composition of claim 21, wherein the lactic acid / glycolic acid ratio is about 90/10 to 50/50 by weight and the weight average molecular weight is about 8000-50000.  23. The pharmaceutical composition according to claim 1, wherein the biodegradable polymer is an aliphatic polyester.  24. The pharmaceutical composition of claim 23, wherein the aliphatic polyester is a copolymer of lactic and glycolic acids.  25. The pharmaceutical composition according to claim 1, which is a suspension.  26. The pharmaceutical composition according to claim 1, used for injection.  27. The use of the pharmaceutical composition according to claim 1 for the preparation of agents for the treatment or prevention of bone diseases.  28. Use of a biodegradable polymer to enhance osteogenesis of stimulating activity.  29. A method for treating or preventing bone diseases in mammals, comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition according to claim 1.  30. The method of claim 29, wherein the bone disease is a bone fracture.  31. An agent for the treatment or prevention of bone diseases with increased osteogenesis stimulating activity, which contains a non-peptide osteogenesis activating substance and a biodegradable polymer.