Compositions and methods for treating bone diseases and broken bones
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IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-031/575
A61K-045/06
A61K-038/18
출원번호
US-0842582
(2015-09-01)
등록번호
US-9694019
(2017-07-04)
발명자
/ 주소
Genberg, Carl
Savage, Paul B.
출원인 / 주소
BRIGHAM YOUNG UNIVERSITY
대리인 / 주소
Workman Nydegger
인용정보
피인용 횟수 :
0인용 특허 :
39
초록▼
Disclosed herein are methods of promoting osteogenesis in a subject, comprising administering a composition comprising a therapeutically effective amount of at least one cationic steroid antimicrobial (CSA). Also disclosed herein are methods of promoting osteogenesis in a subject in need of such pro
Disclosed herein are methods of promoting osteogenesis in a subject, comprising administering a composition comprising a therapeutically effective amount of at least one cationic steroid antimicrobial (CSA). Also disclosed herein are methods of promoting osteogenesis in a subject in need of such promotion, comprising administering a composition comprising a therapeutically effective amount of at least one CSA. Additionally, disclosed herein are compounds and compositions comprising at least one CSA, or a pharmaceutically acceptable salt thereof, for use in the treatment of bone disease or the treatment of broken bones. Kits comprising such compositions and instructions on such methods are also contemplated herein.
대표청구항▼
1. A method of promoting osteogenesis in a subject in need of treatment for a bone disease or healing of a broken bone, comprising: identifying a subject in need of treatment for a bone disease or healing of a broken bone; andadministering to the subject an amount ranging from about 0.1 μg/g to abou
1. A method of promoting osteogenesis in a subject in need of treatment for a bone disease or healing of a broken bone, comprising: identifying a subject in need of treatment for a bone disease or healing of a broken bone; andadministering to the subject an amount ranging from about 0.1 μg/g to about 50 μg/g of body weight and/or an amount ranging from about 0.001 mg to about 1000 mg of at least one cationic steroid antimicrobial (CSA) compound of Formula V, or a pharmaceutically acceptable salt thereof: wherein, rings A, B, C, and D are independently saturated;m, n, p, and q are independently 0 or 1;R1, R2, R4, R5, R6, R8, R9, R10, R11, R13, R14, R15, R16, and R17 are independently selected from the group consisting of hydrogen and substituted or unsubstituted (C1-C6) alkyl;R3, R7, and R12 are independently selected from the group consisting of hydrogen, hydroxyl, substituted or unsubstituted (C1-C18) alkyl, substituted or unsubstituted (C1-C18) hydroxyalkyl, substituted or unsubstituted (C1-C18) alkyloxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylcarboxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkyl amino, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkylamino-(C1-C18) alkylamino, substituted or unsubstituted (C1-C18) aminoalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylamino-(C1-C18) alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted (C2-C6) alkenyl, substituted or unsubstituted (C2-C6) alkynyl, oxo, linking group attached to a second CSA compound, substituted or unsubstituted (C1-C18) aminoalkyloxy, substituted or unsubstituted (C1-C18) aminoalkyloxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) aminoalkylcarboxy, substituted or unsubstituted (C1-C18) aminoalkylaminocarbonyl, substituted or unsubstituted (C1-C18) aminoalkylcarboxamido, substituted or unsubstituted di(C1-C18 alkyl) aminoalkyl, substituted or unsubstituted C-carboxy-(C1-C18) alkyl, H2N—HC(Q5)-C(O)—O—, H2N—HC(Q5)-C(O)—N(H)—, substituted or unsubstituted (C1-C18) azidoalkyloxy, substituted or unsubstituted (C1-C18) cyanoalkyl oxy, P.G.-HN—HC(Q5)-C(O)—O, substituted or unsubstituted (C1-C18) guanidinoalkyloxy, substituted or unsubstituted (C1-C18) quaternary ammonium alkylcarboxy, and substituted or unsubstituted (C1-C18) guanidinoalkylcarboxy, where Q5 is a side chain of an amino acid and P.G. is an amino protecting group, provided that at least two of R3, R7, and R12 are independently selected from the group consisting of aminoalkyloxy, aminoalkylcarboxy, alkylaminoalkyl, and di(alkyl)aminoalkyl; andR18 is selected from the group consisting of hydroxyl, substituted or unsubstituted (C1-C18) alkyl, substituted or unsubstituted (C1-C18) hydroxyalkyl, substituted or unsubstituted (C1-C18) alkyloxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylcarboxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkylamino, substituted or unsubstituted amido, substituted or unsubstituted (C1-C18) aminoalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylamino-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) haloalkyl, substituted or unsubstituted (C2-C6) alkenyl, substituted or unsubstituted (C2-C6) alkynyl, linking group attached to a second CSA compound, substituted or unsubstituted (C1-C18) aminoalkyloxy, substituted or unsubstituted (C1-C18) aminoalkyloxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) aminoalkylcarboxy (C1-C18) alkyl, substituted or unsubstituted (C1-C18) aminoalkylaminocarbonyl, substituted or unsubstituted (C1-C18) aminoalkylcarboxamido, substituted or unsubstituted di(C1-C18 alkyl) aminoalkyl, substituted or unsubstituted C-carboxy-(C1-C18) alkyl, H2N—HC(Q5)-C(O)—O—, H2N—HC(Q5)-C(O)—N(H)—, substituted or unsubstituted (C1-C18) azidoalkyloxy, substituted or unsubstituted (C1-C18) cyanoalkyl oxy, P.G.-HN—HC(Q5)-C(O)—O, substituted or unsubstituted (C1-C18) guanidinoalkyloxy, substituted or unsubstituted (C1-C18) quaternary ammonium alkylcarboxy, and substituted or unsubstituted (C1-C18) guanidinoalkylcarboxy, where Q5 is a side chain of an amino acid and P.G. is an amino protecting group. 2. The method of claim 1, wherein R18 has the following structure: —R20—(C═O)—N—R21R22 wherein, R20 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted aryl; andR21 and R22 are independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-C24 alkyl, substituted or unsubstituted C2-C24 alkenyl, substituted or unsubstituted C2-C24 alkynyl, or a substituted or unsubstituted C6 or C10 aryl, 5 to 10 membered heteroaryl, 5 to 10 membered heterocyclyl, C7-C13 aralkyl, (5 to 10 membered heteroaryl)-C1-C6 alkyl, C3-C10 carbocyclyl, C4-C10 (carbocyclyl)alkyl, (5 to 10 membered heterocyclyl)-C1-C6 alkyl, amido, and amine protecting group, provided that at least one of R21 and R22 is not hydrogen. 3. The method of claim 1, further comprising administering to the subject at least one growth factor. 4. The method of claim 3, wherein the at least one growth factor is at least one of BMP-2 or rhBMP-2. 5. The method of claim 1, wherein the at least one CSA compound facilitates healing of a trauma injury. 6. The method of claim 1, further comprising administering to the subject an antimicrobial agent, other than the at least one CSA compound, to treat or prevent infection. 7. The method of claim 1, wherein the at least one CSA compound treats the bone disease or heals the broken bone and treats or prevent infection. 8. The method of claim 1, wherein the at least one CSA compound is administered from a pharmaceutically acceptable device selected from the group consisting of bandages, surgical dressings, gauzes, adhesive strips, surgical staples, clips, hemostats, intrauterine devices, sutures, trocars, catheters, tubes, and implants. 9. The method of claim 8, wherein the pharmaceutically acceptable device comprises an implant selected from the group consisting of pills, pellets, rods, screws, wafers, discs, sponges, and tablets. 10. The method of claim 1, wherein the bone disease is selected from the group consisting of bone resorption, osteoarthritis, osteoporosis, osteomalacia, osteitis fibrosa cystica, osteochondritis dissecans, osteomalacia, osteoblastogenesis, osteomyelitis, osteopenia, osteonecrosis, and porotic hyperostosis. 11. The method of claim 1, wherein the broken bone results from one or more of a traumatic fracture; a critical sized bone defect; distraction osteogenesis; spine fusion surgery; joint replacement; an orthopaedic implant; or a biopsy. 12. The method of claim 1, wherein the at least one CSA compound is a compound of Formula (I): 13. The method of claim 12, wherein R3, R7, and R12 are independently selected from the group consisting of hydrogen, unsubstituted (C1-C18) alkyl, unsubstituted (C1-C18) hydroxyalkyl, unsubstituted (C1-C18) alkyloxy-(C1-C18) alkyl, unsubstituted (C1-C18) alkylcarboxy-(C1-C18) alkyl, unsubstituted (C1-C18) alkylamino-(C1-C18)alkyl, unsubstituted (C1-C18) alkylamino-(C1-C18) alkylamino, unsubstituted (C1-C18) alkylamino-(C1-C18) alkylamino-(C1-C18) alkylamino, unsubstituted (C1-C18) aminoalkyl, unsubstituted arylamino-(C1-C18) alkyl, unsubstituted (C1-C18) aminoalkyloxy, unsubstituted (C1-C18) aminoalkyloxy-(C1-C18) alkyl, unsubstituted (C1-C18) aminoalkylcarboxy, unsubstituted (C1-C18) aminoalkylaminocarbonyl, unsubstituted (C1-C18) aminoalkylcarboxamido, unsubstituted di(C1-C18 alkyl)aminoalkyl, unsubstituted C-carboxy(C1-C18)alkyl, unsubstituted (C1-C18) guanidinoalkyloxy, unsubstituted (C1-C18) quaternary ammonium alkylcarboxy, and unsubstituted (C1-C18) guanidinoalkyl carboxy; and R18 is selected from the group consisting of substituted or unsubstituted (C1-C18) alkylcarboxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkyl amino-(C1-C18) alkyl, substituted or unsubstituted amido, substituted or unsubstituted (C1-C18) aminoalkyl, linking group attached to a second CSA compound, substituted or unsubstituted (C1-C18) aminoalkyloxy, substituted or unsubstituted (C1-C18) aminoalkyloxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) aminoalkylcarboxy (C1-C18) alkyl, and substituted or unsubstituted di(C1-C18 alkyl) aminoalkyl. 14. The method of claim 12, wherein R3, R7, and R12 are independently selected from the group consisting of hydrogen, unsubstituted (C1-C6) alkyl, unsubstituted (C1-C6) hydroxyalkyl, unsubstituted (C1-C16) alkyloxy-(C1-C5) alkyl, unsubstituted (C1-C16) alkylcarboxy-(C1-C5) alkyl, unsubstituted (C1-C16) alkylamino-(C1-C5)alkyl, (C1-C16) alkylamino-(C1-C5) alkylamino, unsubstituted (C1-C16) alkylamino-(C1-C16) alkylamino-(C1-C5) alkylamino, unsubstituted (C1-C16) aminoalkyl, unsubstituted arylamino-(C1-C5) alkyl, unsubstituted (C1-C5) aminoalkyloxy, unsubstituted (C1-C16) aminoalkyloxy-(C1-C5) alkyl, unsubstituted (C1-C5) aminoalkylcarboxy, unsubstituted (C1-C5) aminoalkylaminocarbonyl, unsubstituted (C1-C5) aminoalkylcarboxamido, unsubstituted di(C1-C5 alkyl)amino-(C1-C5) alkyl, unsubstituted C-carboxy(C1-C18)alkyl, unsubstituted (C1-C5) guanidinoalkyloxy, unsubstituted (C1-C16) quaternary ammonium alkylcarboxy, and unsubstituted (C1-C16) guanidinoalkylcarboxy. 15. The method of claim 14, wherein R1, R2, R4, R5, R6, R8, R10, R11, R14, R16, and R17 are each hydrogen; and R9 and R13 are each methyl. 16. The method of claim 15, wherein R3, R7, and R12 are independently selected from the group consisting of aminoalkyloxy and aminoalkylcarboxy; andR18 is selected from the group consisting of alkylaminoalkyl; alkoxycarbonylalkyl; alkylcarbonyloxyalkyl; di(alkyl)aminoalkyl; C-carboxyalkyl; alkylaminoalkyl; alkyoxycarbonylalkyl; and alkylcarboxyalkyl. 17. The method of claim 12, wherein R18 has the following structure: —R20—(C═O)—N—R21R22 wherein, R20 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted aryl; andR21 and R22 are independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-C24 alkyl, substituted or unsubstituted C2-C24 alkenyl, substituted or unsubstituted C2-C24 alkynyl, substituted or unsubstituted C6 or C10 aryl, 5 to 10 membered heteroaryl, 5 to 10 membered heterocyclyl, C7-C13 aralkyl, (5 to 10 membered heteroaryl)-C1-C6 alkyl, C3-C10 carbocyclyl, C4-C10 (carbocyclyl)alkyl, (5 to 10 membered heterocyclyl)-C1-C6 alkyl, amido, and amine protecting group, provided that at least one of R21 and R22 is not hydrogen. 18. The method of claim 12, wherein R3, R7, and R12 are aminoalkyloxy. 19. The method of claim 18, wherein R18 is alkylamidoalkyl. 20. The method of claim 12, wherein R18 is alkylaminocarbonylalkyl. 21. The method of claim 12, wherein R18 is di(alkyl)aminoalkyl. 22. The method of claim 12, wherein R18 is alkylcarboxyalkyl. 23. The method of claim 12, wherein R3, R7, and R12 are aminoalkylcarboxy. 24. The method of claim 12, wherein R18 is alkylaminoalkyl. 25. The method of claim 17, wherein R3, R7, and R12 are independently selected from the group consisting of amino-C3-alkyloxy; amino-C3-alkyl-carboxy; C8-alkylamino-C5-alkyl; C8-alkoxycarbonyl-C4-alkyl; C8-alkylcarbonyl-C4-alkyl; di-(C5-alkyl)amino-C5-alkyl; C-carboxy-C4-alkyl; C13-alkylamino-C5-alkyl; C6-alkoxycarbonyl-C4-alkyl; and C6-alkylcarboxy-C4-alkyl. 26. The method of claim 1, wherein the at least one CSA compound is selected from the group consisting of: and pharmaceutically acceptable salts thereof. 27. The method of claim 1, wherein the pharmaceutically acceptable salt is a hydrochloride salt. 28. The method of claim 27, wherein the pharmaceutically acceptable salt is a tri-hydrochloride salt. 29. A method of promoting osteogenesis in a subject in need of treatment for a bone disease or healing of a broken bone, comprising: identifying a subject in need of treatment for a bone disease or healing of a broken bone; andadministering to the subject an amount ranging from about 0.1 μg/g to about 50 μg/g of body weight and/or an amount ranging from about 0.001 mg to about 1000 mg of at least one cationic steroid antimicrobial (CSA) compound of Formula 1a, or a pharmaceutically acceptable salt thereof: wherein, R3, R7, and R12 are independently selected from the group consisting of hydrogen, hydroxyl, substituted or unsubstituted (C1-C18) alkyl, substituted or unsubstituted (C1-C18) hydroxyalkyl, substituted or unsubstituted (C1-C18) alkyloxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylcarboxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkylamino, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkylamino-(C1-C18) alkylamino, substituted or unsubstituted (C1-C18) aminoalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylamino-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) haloalkyl, substituted or unsubstituted (C2-C6) alkenyl, substituted or unsubstituted (C2-C6) alkynyl, oxo, linking group attached to a second CSA compound, substituted or unsubstituted (C1-C18) aminoalkyloxy, substituted or unsubstituted (C1-C18) aminoalkyloxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) aminoalkylcarboxy, substituted or unsubstituted (C1-C18) aminoalkylaminocarbonyl, substituted or unsubstituted (C1-C18) aminoalkylcarboxamido, substituted or unsubstituted di(C1-C18 alkyl) aminoalkyl, substituted or unsubstituted C-carboxy-(C1-C18) alkyl, H2N—HC(Q5)-C(O)—O—, H2N—HC(Q5)-C(O)—N(H)—, substituted or unsubstituted (C1-C18) azidoalkyloxy, substituted or unsubstituted (C1-C18) cyanoalkyloxy, P.G.-HN—HC(Q5)-C(O)—O, substituted or unsubstituted (C1-C18) guanidinoalkyloxy, substituted or unsubstituted (C1-C18) quaternary ammonium alkylcarboxy, and substituted or unsubstituted (C1-C18) guanidinoalkylcarboxy, where Q5 is a side chain of an amino acid and P.G. is an amino protecting group, provided that at least two of R3, R7, and R12 are independently selected from the group consisting of aminoalkyloxy, aminoalkylcarboxy, alkylaminoalkyl, and di(alkyl)aminoalkyl; andR18 is selected from the group consisting of hydroxyl, substituted or unsubstituted (C1-C18) alkyl, substituted or unsubstituted (C1-C18) hydroxyalkyl, substituted or unsubstituted (C1-C18) alkyloxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylcarboxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkylamino, substituted or unsubstituted amido, substituted or unsubstituted (C1-C18) aminoalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylamino-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) haloalkyl, substituted or unsubstituted (C2-C6) alkenyl, substituted or unsubstituted (C2-C6) alkynyl, linking group attached to a second CSA compound, substituted or unsubstituted (C1-C18) aminoalkyloxy, substituted or unsubstituted (C1-C18) aminoalkyloxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) aminoalkylcarboxy (C1-C18) alkyl, substituted or unsubstituted (C1-C18) aminoalkylaminocarbonyl, substituted or unsubstituted (C1-C18) aminoalkylcarboxamido, substituted or unsubstituted di(C1-C18 alkyl) aminoalkyl, substituted or unsubstituted C-carboxy-(C1-C18) alkyl, H2N—HC(Q5)-C(O)—O—, H2N—HC(Q5)-C(O)—N(H)—, substituted or unsubstituted (C1-C18) azidoalkyloxy, substituted or unsubstituted (C1-C18) cyanoalkyloxy, P.G.-HN—HC (Q5)-C(O)—O, substituted or unsubstituted (C1-C18) guanidinoalkyloxy, substituted or unsubstituted (C1-C18) quaternary ammonium alkylcarboxy, and substituted or unsubstituted (C1-C18) guanidinoalkylcarboxy, where Q5 is a side chain of an amino acid and P.G. is an amino protecting group. 30. The method of claim 29, wherein Rig has the following structure: —R20—(C═O)—N—R21R22 wherein, R20 is omitted or substituted or unsubstituted alkyl, alkenyl, alkynyl, or aryl; andR21 and R22 are independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted aryl, provided that at least one of R21 and R22 is not hydrogen. 31. A method of promoting osteogenesis in a subject in need of treatment for a bone disease or healing of a broken bone, comprising: identifying a subject in need of treatment for a bone disease or healing of a broken bone; andadministering to the subject, by means of a pharmaceutically acceptable device, an effective amount of at least one cationic steroid antimicrobial (CSA) compound of Formula V, or a pharmaceutically acceptable salt thereof, and wherein the pharmaceutically acceptable device or a coating applied to the pharmaceutically acceptable device includes about 0.1% to about 50% by weight of the at least one CSA compound: wherein, rings A, B, C, and D are independently saturated;m, n, p, and q are independently 0 or 1;R1, R2, R4, R5, R6, R8, R9, R10, R11, R13, R14, R15, R16, and R17 are independently selected from the group consisting of hydrogen and substituted or unsubstituted (C1-C6) alkyl;R3, R7, and R12 are independently selected from the group consisting of hydrogen, hydroxyl, substituted or unsubstituted (C1-C18) alkyl, substituted or unsubstituted (C1-C18) hydroxyalkyl, substituted or unsubstituted (C1-C18) alkyloxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylcarboxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkyl amino, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkylamino-(C1-C18) alkylamino, substituted or unsubstituted (C1-C18) aminoalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylamino-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) haloalkyl, substituted or unsubstituted (C2-C6) alkenyl, substituted or unsubstituted (C2-C6) alkynyl, oxo, linking group attached to a second CSA compound, substituted or unsubstituted (C1-C18) aminoalkyloxy, substituted or unsubstituted (C1-C18) aminoalkyloxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) aminoalkylcarboxy, substituted or unsubstituted (C1-C18) aminoalkylaminocarbonyl, substituted or unsubstituted (C1-C18) aminoalkylcarboxamido, substituted or unsubstituted di(C1-C18 alkyl) aminoalkyl, substituted or unsubstituted C-carboxy-(C1-C18) alkyl, H2N—HC(Q5)-C(O)—O—, H2N—HC(Q5)-C(O)—N(H)—, substituted or unsubstituted (C1-C18) azidoalkyloxy, substituted or unsubstituted (C1-C18) cyanoalkyloxy, P.G.-HN—HC(Q5)-C(O)—O, substituted or unsubstituted (C1-C18) guanidinoalkyloxy, substituted or unsubstituted (C1-C18) quaternary ammonium alkylcarboxy, and substituted or unsubstituted (C1-C18) guanidinoalkylcarboxy, where Q5 is a side chain of an amino acid and P.G. is an amino protecting group, provided that at least two of R3, R7, and R12 are independently selected from the group consisting of aminoalkyloxy, aminoalkylcarboxy, alkylaminoalkyl, and di(alkyl)aminoalkyl; andR18 is selected from the group consisting of hydroxyl, substituted or unsubstituted (C1-C18) alkyl, substituted or unsubstituted (C1-C18) hydroxyalkyl, substituted or unsubstituted (C1-C18) alkyloxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylcarboxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkylamino, substituted or unsubstituted amido, substituted or unsubstituted (C1-C18) aminoalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylamino-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) haloalkyl, substituted or unsubstituted (C2-C6) alkenyl, substituted or unsubstituted (C2-C6) alkynyl, linking group attached to a second CSA compound, substituted or unsubstituted (C1-C18) aminoalkyloxy, substituted or unsubstituted (C1-C18) aminoalkyloxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) aminoalkylcarboxy (C1-C18) alkyl, substituted or unsubstituted (C1-C18) aminoalkylaminocarbonyl, substituted or unsubstituted (C1-C18) aminoalkylcarboxamido, substituted or unsubstituted di(C1-C18 alkyl) aminoalkyl, substituted or unsubstituted C-carboxy-(C1-C18) alkyl, H2N—HC(Q5)-C(O)—O—, H2N—HC(Q5)-C(O)—N(H)—, substituted or unsubstituted (C1-C18) azidoalkyloxy, substituted or unsubstituted (C1-C18) cyanoalkyloxy, P.G.-HN—HC(Q5)-C(O)—O, substituted or unsubstituted (C1-C18) guanidinoalkyloxy, substituted or unsubstituted (C1-C18) quaternary ammonium alkylcarboxy, and substituted or unsubstituted (C1-C18) guanidinoalkylcarboxy, where Q5 is a side chain of an amino acid and P.G. is an amino protecting group. 32. The method of claim 31, wherein Rig has the following structure: —R20—(C═O)—N—R21R22 wherein, R20 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted aryl; andR21 and R22 are independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-C24 alkyl, substituted or unsubstituted C2-C24 alkenyl, substituted or unsubstituted C2-C24 alkynyl, substituted or unsubstituted C6 or C10 aryl, 5 to 10 membered heteroaryl, 5 to 10 membered heterocyclyl, C7-C13 aralkyl, (5 to 10 membered heteroaryl)-C1-C6 alkyl, C3-C10 carbocyclyl, C4-C10 (carbocyclyl)alkyl, (5 to 10 membered heterocyclyl)-C1-C6 alkyl, amido, and amine protecting group, provided that at least one of R21 and R22 is not hydrogen. 33. The method of claim 31, wherein the at least one CSA compound is selected from the group consisting of: and pharmaceutically acceptable salts thereof. 34. A method of promoting osteogenesis in a subject in need of treatment for a bone disease or healing a broken bone, comprising: identifying a subject in need of treatment for a bone disease or healing a broken bone; andadministering to the subject an effective amount of at least one cationic steroid antimicrobial (CSA) compound for promoting osteogenesis selected from the group consisting of: and pharmaceutically acceptable salts thereof. 35. The method of claim 34, wherein the effective amount of at least one CSA compound is in a range from about 0.1 μg/g to about 50 μg/g of body weight and/or in a range from about 0.001 mg to about 1000 at least one CSA compound. 36. A method of promoting osteogenesis in a subject in need of treatment for a bone disease or healing a broken bone, comprising: identifying a subject in need of treatment for a bone disease or healing a broken bone; andadministering to the subject at least one cationic steroid antimicrobial (CSA) compound of Formula Ia, or a pharmaceutically acceptable salt thereof, in an effective amount (i) ranging from about 0.1 μg/g to about 50 μg/g of body weight, and/or (ii) ranging from about 0.001 mg to about 1000 mg, and/or (iii) by means of a pharmaceutically acceptable device and/or a coating applied thereto thaty includes about 0.1% to about 50% by weight of the at least one CSA compound: wherein, R3, R7, and R12 are independently selected from the group consisting of independently selected from the group consisting of hydrogen, unsubstituted (C1-C22) alkyl, unsubstituted (C1-C22) hydroxyalkyl, unsubstituted (C1-C22) alkyloxy-(C1-C22) alkyl, unsubstituted (C1-C22) alkylcarboxy-(C1-C22) alkyl, unsubstituted (C1-C22) alkylamino-(C1-C22)alkyl, unsubstituted (C1-C22) alkylamino-(C1-C22) alkylamino, unsubstituted (C1-C22) alkylamino-(C1-C22) alkylamino-(C1-C18) alkylamino, unsubstituted (C1-C22) aminoalkyl, unsubstituted arylamino-(C1-C22) alkyl, unsubstituted (C1-C22) aminoalkyloxy, unsubstituted (C1-C22) aminoalkyloxy-(C1-C22) alkyl, unsubstituted (C1-C22) aminoalkylcarboxy, unsubstituted (C1-C22) aminoalkyl-aminocarbonyl, unsubstituted (C1-C22) aminoalkylcarboxamido, unsubstituted di(C1-C22 alkyl)aminoalkyl, unsubstituted (C1-C22) guanidinoalkyloxy, unsubstituted (C1-C22) quaternary ammonium alkylcarboxy, and unsubstituted (C1-C22) guanidinoalkyl carboxy; andR18 is selected from the group consisting of substituted or unsubstituted (C1-C18) alkylcarboxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkyl, substituted or unsubstituted amido, substituted or unsubstituted (C1-C18) aminoalkyl, linking group attached to a second CSA compound, substituted or unsubstituted (C1-C18) aminoalkyloxy, substituted or unsubstituted (C1-C18) aminoalkyloxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) aminoalkylcarboxy (C1-C18) alkyl, and substituted or unsubstituted di(C1-C18 alkyl) aminoalkyl. 37. The method of claim 36, wherein R18 has the following structure: —R20—(C═O)—N—R21R22 wherein, R20 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted aryl; andR21 and R22 are independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-C24 alkyl, substituted or unsubstituted C2-C24 alkenyl, substituted or unsubstituted C2-C24 alkynyl, or substituted or unsubstituted C6 or C10 aryl, 5 to 10 membered heteroaryl, 5 to 10 membered heterocyclyl, C7-C13 aralkyl, (5 to 10 membered heteroaryl)-C1-C6 alkyl, C3-C10 carbocyclyl, C4-C10 (carbocyclyl)alkyl, (5 to 10 membered heterocyclyl)-C1-C6 alkyl, amido, and amine protecting group, provided that at least one of R21 and R22 is not hydrogen.
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