WO2018057624A4 - Methods and compositions for stimulation and enhancement of regeneration of tissues - Google Patents

Methods and compositions for stimulation and enhancement of regeneration of tissues Download PDF

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Publication number
WO2018057624A4
WO2018057624A4 PCT/US2017/052516 US2017052516W WO2018057624A4 WO 2018057624 A4 WO2018057624 A4 WO 2018057624A4 US 2017052516 W US2017052516 W US 2017052516W WO 2018057624 A4 WO2018057624 A4 WO 2018057624A4
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Prior art keywords
aminosterol
tissue
dose
active agent
substitution
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Application number
PCT/US2017/052516
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French (fr)
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WO2018057624A1 (en
Inventor
Michael Alan Zasloff
Viravuth Pho YIN
Kevin B. Strange
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Mount Desert Island Biological Laboratory
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Priority claimed from US15/272,098 external-priority patent/US20170007624A1/en
Application filed by Mount Desert Island Biological Laboratory filed Critical Mount Desert Island Biological Laboratory
Priority to CA3037712A priority Critical patent/CA3037712A1/en
Priority to EP17853814.6A priority patent/EP3515450A4/en
Priority to JP2019537034A priority patent/JP2019529558A/en
Publication of WO2018057624A1 publication Critical patent/WO2018057624A1/en
Publication of WO2018057624A4 publication Critical patent/WO2018057624A4/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

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  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Neurology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Steroid Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
  • Materials For Medical Uses (AREA)

Abstract

Methods and pharmaceutical compositions are provided for enhancing or stimulating regeneration of a tissue in a subject. In one aspect, the invention provides a method including administering to a subject in need thereof a therapeutically effective amount of an aminosterol or a pharmaceutically acceptable salt thereof to stimulate or enhance regeneration of a tissue. In another aspect, the invention provides a method including administering to a subject a therapeutically effective amount of an aminosterol or a pharmaceutically acceptable salt thereof to stimulate or enhance regeneration of a tissue to treat or prevent a disease, disorder, trauma, or condition resulting from an injury of the tissue. In an additional aspect, the invention provides a pharmaceutical composition comprising a therapeutically effective amount of an aminosterol to stimulate or enhance regeneration of a tissue.

Claims

AMENDED CLAIMS received by the International Bureau on 02 April 2018 (02.04.2018)
1. A method of treatment for a subj ect in need thereof comprising :
administering to the subject a therapeutically effective amount of an aminosterol or a pharmaceutically acceptable salt thereof to stimulate or enhance regeneration or growth of a tissue;
wherein the tissue is a skeletal muscle tissue or a skeletal system tissue.
2. The method of claim 1 further comprising:
prior to the administering step, identifying the subject having a condition selected from the group consisting of a disorder, a disease, a trauma and a health problem;
wherein the condition affects the tissue.
3. The method of claim 2, wherein the condition comprises muscular dystrophy.
4. The method of claim 1, wherein the aminosterol is MSI-1436.
5. The method of claim 1, wherein the aminosterol is an isomer of MSI-1436.
6. The method of claim 1, wherein the aminosterol comprises a sterol nucleus and a polyamine, attached at any position on the sterol, such that the aminosterol exhibits a net charge of at least + 1, the charge being contributed by the polyamine.
7. The method of claim 1, wherein the aminosterol is modified to include at least one of the following:
a substitution of the sulfate, wherein the substitution is selected from the group consisting of a sulfonate, a phosphate, a carboxylate, and an anionic moiety, and wherein the substitution is chosen to circumvent metabolic removal of the sulfate moiety and oxidation of the cholesterol side chain;
a replacement of a hydroxyl group by a non-metabolizable polar substituent to prevent its metabolic oxidation or conjugation; and
a substitution of at least one ring hydrogen atom to prevent oxidative or reductive metabolism of the steroid ring system.
8. The method of claim 7, wherein the non-metabolizable polar substituent is a fluorine atom.
AMENDED SHEET (ARTICLE 19)
44
9. The method of claim 1, wherein the aminosterol is a derivative of MSI-1436 modified through medical chemistry to improve at least one of bio-distribution, ease of administration, metabolic stability, and a combination of at least two thereof.
10. The method of claim 1, wherein the therapeutically effective amount of the aminosterol is from about 0.07 mg/kg to about 2.67 mg/kg body weight in a human.
1 1. The method claim 1, wherein the therapeutically effective amount of the aminosterol is administered in combination with at least one additional active agent to achieve an additive or synergistic effect.
12. The method of claim 10, wherein the active agent is administered according to one of the group of administration methods consisting of:
i) administering simultaneously but separately at least one dose of the active agent and at least one dose of the aminosterol;
ii) administering together in an admixture at least one dose of the active agent and at least one dose of the aminosterol;
iii) administering sequentially at least one dose of the active agent and at least one dose of the aminosterol, the at least one dose of the active agent being administered prior to administration of the at least one dose of the aminosterol;
iv) administering sequentially at least one dose of the active agent and at least one dose of the aminosterol, the at least one dose of the active agent being administered following administration of the at least one dose of the aminosterol; and
v) administering sequentially and together in an admixture at least one dose of the active agent and at least one dose of the aminosterol.
13. The method of claim 1, wherein the therapeutically effective amount of aminosterol is administered in the form of a liquid, a capsule, a tablet, intravenously, intraperitoneally, inhaled, or topically.
14. The method of claim 1, wherein the subject is a mammal.
15. The method of claim 1 , wherein the subj ect is a human .
16. A method of treatment for a subject in need thereof comprising:
AMENDED SHEET (ARTICLE 19) administering to the subject a therapeutically effective amount of an aminosterol or a pharmaceutically acceptable salt thereof to stimulate or enhance regeneration or growth of a tissue to treat or prevent a condition selected from the group consisting of a disease, a disorder, a trauma and a health problem,
wherein the condition affects the tissue; and
wherein the condition comprises muscular dystrophy.
17. The method of claim 16, further comprising:
prior to the administering step, identifying the subject having the condition.
18. The method of claim 16, wherein the tissue is selected from the group consisting of: a liver tissue, a lung tissue, a skin soft tissue, a skeletal muscle tissue, a cardiac muscle tissue, a vascular tree tissue, a central nervous system tissue, a peripheral nervous system tissue, a gastrointestinal tract tissue, a exocrine and endocrine pancreas tissue, a skeletal system tissue, and a hematopoietic tissue.
19. The method of claim 16, wherein the aminosterol is MSI-1436.
20. The method of claim 16, wherein the aminosterol is an isomer of MSI-1436.
21. The method of claim 16, wherein the aminosterol comprises a sterol nucleus and a polyamine, attached at any position on the sterol, such that the aminosterol exhibits a net charge of at least + 1, the charge being contributed by the polyamine.
22. The method of claim 16, wherein the aminosterol is modified to include at least one of the following:
a substitution of the sulfate, wherein the substitution is selected from the group consisting of a sulfonate, a phosphate, a carboxylate, and an anionic moiety, and wherein the substitution is chosen to circumvent metabolic removal of the sulfate moiety and oxidation of the cholesterol side chain; and
a replacement of a hydroxyl group by a non-metabolizable polar substituent to prevent its metabolic oxidation or conjugation; and
a substitution of at least one ring hydrogen atom to prevent oxidative or reductive metabolism of the steroid ring system.
AMENDED SHEET (ARTICLE 19)
23. The method of claim 22, wherein the non-metabolizable polar substituent is a fluorine atom.
24. The method of claim 16, wherein the aminosterol is a derivative of MSI-1436 modified through medical chemistry to improve at least one of bio-distribution, ease of administration, metabolic stability, and a combination of at least two thereof.
25. The method of claim 16, wherein the therapeutically effective amount of the aminosterol is from about 0.07 mg/kg to about 2.67 mg/kg body weight in a human.
26. The method claim 16, wherein a therapeutically effective amount of the aminosterol is administered in combination with at least one additional active agent to achieve an additive or synergistic effect.
27. The method of claim 26, wherein the active agent is administered according to one of the group of administration methods consisting of:
i) administering simultaneously but separately at least one dose of the active agent and at least one dose of the aminosterol;
ii) administering together in an admixture at least one dose of the active agent and at least one dose of the aminosterol;
iii) administering sequentially at least one dose of the active agent and at least one dose of the aminosterol, the at least one dose of the active agent being administered prior to administration of the at least one dose of the aminosterol;
iv) administering sequentially at least one dose of the active agent and at least one dose of the aminosterol, the at least one dose of the active agent being administered following administration of the at least one dose of the aminosterol; and
v) administering sequentially and together in an admixture at least one dose of the active agent and at least one dose of the aminosterol.
28. The method of claim 16, wherein the therapeutically effective amount of aminosterol is administered in the form of a liquid, capsule, tablet, intravenously, intraperitoneally, inhaled, or topically.
29. The method of claim 16, wherein the subject is a mammal.
30. The method of claim 16, wherein the subject is a human.
AMENDED SHEET (ARTICLE 19)
47
31. A pharmaceutical composition comprising
a therapeutically effective amount of an aminosterol or a pharmaceutically acceptable salt thereof to stimulate or enhance regeneration or growth of a tissue;
wherein the tissue is a skeletal muscle tissue or a skeletal system tissue.
32. A kit containing the pharmaceutical composition of claim 31.
33. The composition of claim 31, wherein the aminosterol is MSI-1436.
34. The composition of claim 31, wherein the aminosterol is an isomer of MSI-1436.
35. The composition of claim 31, wherein the aminosterol comprises a sterol nucleus and a polyamine, attached at any position on the sterol, such that the aminosterol exhibits a net charge of at least + 1, the charge being contributed by the polyamine.
36. The composition of claim 31, wherein the aminosterol is modified to include at least one of the following:
a substitution of the sulfate, wherein the substitution is selected from the group consisting of a sulfonate, a phosphate, a carboxylate, and an anionic moiety, and wherein the substitution is chosen to circumvent metabolic removal of the sulfate moiety and oxidation of the cholesterol side chain;
a replacement of a hydroxyl group by a non-metabolizable polar substituent to prevent its metabolic oxidation or conjugation; and
a substitution of at least one ring hydrogen atom to prevent oxidative or reductive metabolism of the steroid ring system.
37. The composition of claim 36, wherein the non-metabolizable polar substituent is a fluorine atom.
38. The composition of claim 31, wherein the aminosterol is a derivative of MSI-1436 modified through medical chemistry to improve at least one of bio-distribution, ease of administration, metabolic stability, and a combination of at least two thereof.
39. The composition of claim 31, wherein the composition includes at least one additional active agent to achieve an additive or synergistic effect.
AMENDED SHEET (ARTICLE 19)
48
40. The composition of claim 31, wherein the therapeutically effective amount comprises the aminosterol in a range from about 0.07 mg/kg to about 2.67 mg/kg body weight in a human.
41. A pharmaceutical composition comprising
a therapeutically effective amount of an aminosterol or a pharmaceutically acceptable salt thereof to stimulate or enhance regeneration or growth of a tissue for the treatment or prevention of a condition selected from the group consisting of a disease, disorder, trauma and health problem which affects the tissue; and
wherein the condition comprises muscular dystrophy.
42. A kit containing the pharmaceutical composition of claim 41.
43. The composition of claim 41, wherein the aminosterol is MSI-1436.
44. The composition of claim 41, wherein the aminosterol is an isomer of MSI-1436.
45. The composition of claim 41, wherein the aminosterol comprises a sterol nucleus and a polyamine, attached at any position on the sterol, such that the aminosterol exhibits a net charge of at least + 1, the charge being contributed by the polyamine.
46. The composition of claim 41, wherein the aminosterol is modified to include at least one of the following:
a substitution of the sulfate, wherein the substitution is selected from the group consisting of a sulfonate, a phosphate, a carboxylate, and an anionic moiety, and wherein the substitution is chosen to circumvent metabolic removal of the sulfate moiety and oxidation of the cholesterol side chain;
a replacement of a hydroxyl group by a non-metabolizable polar substituent to prevent its metabolic oxidation or conjugation; and
a substitution of at least one ring hydrogen atom to prevent oxidative or reductive metabolism of the steroid ring system.
47. The composition of claim 46, wherein the non-metabolizable polar substituent is a fluorine atom.
48. The composition of claim 41, wherein the aminosterol is a derivative of MSI-1436 modified through medical chemistry to improve at least one of bio-distribution, ease of administration, metabolic stability, and a combination of at least two thereof.
AMENDED SHEET (ARTICLE 19)
49
49. The composition of claim 41, wherein the composition includes at least one additional active agent to achieve an additive or synergistic effect.
50. The composition of claim 41, wherein the therapeutically effective amount comprises the aminosterol in a range from about 0.07 mg/kg to about 2.67 mg/kg body weight in a human.
51. A method of treatment for a subject in need thereof comprising:
administering to the subject a therapeutically effective amount of an aminosterol or a pharmaceutically acceptable salt thereof to stimulate or enhance regeneration or growth of a plurality of stem cells to treat or prevent a condition selected from a disease, a disorder, a trauma, and a health problem.
52. The method of claim 51, further comprising:
prior to the administering step, identifying the subject having the condition.
53. The method of claim 51, wherein the plurality of the stem cells form at least part of a tissue selected from the group consisting of: a liver tissue, a lung tissue, a skin soft tissue, a skeletal muscle tissue, a cardiac muscle tissue, a vascular tree tissue, a central nervous system tissue, a peripheral nervous system tissue, a gastrointestinal tract tissue, a exocrine and endocrine pancreas tissue, a skeletal system tissue, and a hematopoietic tissue.
54. The method of claim 51, wherein the aminosterol is MSI-1436.
55. The method of claim 51, wherein the aminosterol is an isomer of MSI-1436.
56. The method of claim 51, wherein the aminosterol comprises a sterol nucleus and a polyamine, attached at any position on the sterol, such that the aminosterol exhibits a net charge of at least + 1, the charge being contributed by the polyamine.
57. The method of claim 51, wherein the aminosterol is modified to include at least one of the following:
a substitution of the sulfate, wherein the substitution is selected from the group consisting of a sulfonate, a phosphate, a carboxylate, and an anionic moiety, and wherein the substitution is chosen to circumvent metabolic removal of the sulfate moiety and oxidation of the cholesterol side chain;
a replacement of a hydroxyl group by a non-metabolizable polar substituent to prevent its metabolic oxidation or conjugation; and
AMENDED SHEET (ARTICLE 19)
50 a substitution of at least one ring hydrogen atom to prevent oxidative or reductive metabolism of the steroid ring system.
58. The method of claim 57, wherein the non-metabolizable polar substituent is a fluorine atom.
59. The method of claim 51, wherein the aminosterol is a derivative of MSI-1436 modified through medical chemistry to improve at least one of bio-distribution, ease of administration, metabolic stability, and a combination of at least two thereof.
60. The method of claim 51, wherein the therapeutically effective amount of the aminosterol is from about 0.07 mg/kg to about 2.67 mg/kg body weight in a human.
61. The method claim 51 , wherein the therapeutically effective amount of the aminosterol is administered in combination with at least one additional active agent to achieve an additive or synergistic effect.
62. The method of claim 60, wherein the active agent is administered according to one of the group of administration methods consisting of:
i) administering simultaneously but separately at least one dose of the active agent and at least one dose of the aminosterol;
ii) administering together in an admixture at least one dose of the active agent and at least one dose of the aminosterol;
iii) administering sequentially at least one dose of the active agent and at least one dose of the aminosterol, the at least one dose of the active agent being administered prior to administration of the at least one dose of the aminosterol;
iv) administering sequentially at least one dose of the active agent and at least one dose of the aminosterol, the at least one dose of the active agent being administered following administration of the at least one dose of the aminosterol; and
v) administering sequentially and together in an admixture at least one dose of the active agent and at least one dose of the aminosterol.
63. The method of claim 51, wherein the therapeutically effective amount of aminosterol is administered in the form of a liquid, a capsule, a tablet, intravenously, intraperitoneally, inhaled, or topically.
AMENDED SHEET (ARTICLE 19)
51
64. The method of claim 51, wherein the subject is a mammal.
65. The method of claim 51 , wherein the subj ect is a human.
66. A pharmaceutical composition comprising:
a therapeutically effective amount of an aminosterol or a pharmaceutically acceptable salt thereof for stimulation or enhancement of growth or regeneration of a plurality of stem cells for the treatment or prevention of a condition selected from the group consisting of a disease, disorder, trauma and health problem.
67. A kit containing the pharmaceutical composition of claim 66.
68. The composition of claim 66, wherein the aminosterol is MSI-1436.
69. The composition of claim 66, wherein the aminosterol is an isomer of MSI-1436.
70. The composition of claim 66, wherein the aminosterol comprises a sterol nucleus and a polyamine, attached at any position on the sterol, such that the aminosterol exhibits a net charge of at least + 1, the charge being contributed by the polyamine.
71. The composition of claim 66, wherein the aminosterol is modified to include at least one of the following :
a substitution of the sulfate, wherein the substitution is selected from the group consisting of a sulfonate, a phosphate, a carboxylate, and an anionic moiety, and wherein the substitution is chosen to circumvent metabolic removal of the sulfate moiety and oxidation of the cholesterol side chain;
a replacement of a hydroxyl group by a non-metabolizable polar substituent to prevent its metabolic oxidation or conjugation; and
a substitution of at least one ring hydrogen atom to prevent oxidative or reductive metabolism of the steroid ring system.
72. The composition of claim 71, wherein the non-metabolizable polar substituent is a fluorine atom.
73. The composition of claim 66, wherein the aminosterol is a derivative of MSI-1436 modified through medical chemistry to improve at least one of bio-distribution, ease of administration, metabolic stability, and a combination of at least two thereof.
AMENDED SHEET (ARTICLE 19)
52
74. The composition of claim 66, wherein the composition includes at least one additional active agent to achieve an additive or synergistic effect.
75. The composition of claim 66, wherein the therapeutically effective amount comprises the aminosterol in a range from about 0.07 mg/kg to about 2.67 mg/kg body weight in a human.
76. The composition of claim 66, wherein the plurality of stem cells form at least part of a tissue selected from the group consisting of: a liver tissue, a lung tissue, a skin soft tissue, a skeletal muscle tissue, a cardiac muscle tissue, a vascular tree tissue, a central nervous system tissue, a peripheral nervous system tissue, a gastrointestinal tract tissue, a exocrine and endocrine pancreas tissue, a skeletal system tissue, and a hematopoietic tissue.
77. A method of growing in vitro a plurality of stem cells comprising:
adding an effective amount of an aminosterol or a pharmaceutically acceptable salt thereof to the plurality of stem cells cultured from a tissue extracted from a subject thereby stimulating or enhancing growth in vitro of the plurality of stem cells.
78. The method of claim 77, wherein the tissue is selected from the group consisting of: a liver tissue, a lung tissue, a skin soft tissue, a skeletal muscle tissue, a cardiac muscle tissue, a vascular tree tissue, a central nervous system tissue, a peripheral nervous system tissue, a gastrointestinal tract tissue, a exocrine and endocrine pancreas tissue, a skeletal system tissue, and a hematopoietic tissue.
79. The method of claim 77, wherein the aminosterol is MSI-1436.
80. The method of claim 77, wherein the aminosterol is an isomer of MSI-1436.
81. The method of claim 77, wherein the aminosterol comprises a sterol nucleus and a polyamine, attached at any position on the sterol, such that the aminosterol exhibits a net charge of at least + 1, the charge being contributed by the polyamine.
82. The method of claim 77, wherein the aminosterol is modified to include at least one of the following:
a substitution of the sulfate, wherein the substitution is selected from the group consisting of a sulfonate, a phosphate, a carboxylate, and an anionic moiety, and wherein the substitution is chosen to circumvent metabolic removal of the sulfate moiety and oxidation of the cholesterol side chain;
AMENDED SHEET (ARTICLE 19)
53 a replacement of a hydroxyl group by a non-metabolizable polar substituent to prevent its metabolic oxidation or conjugation; and
a substitution of at least one ring hydrogen atom to prevent oxidative or reductive metabolism of the steroid ring system.
83. The method of claim 82, wherein the non-metabolizable polar substituent is a fluorine atom.
84. The method of claim 77, wherein the subject is a mammal.
85. The method of claim 77, wherein the subject is a human.
AMENDED SHEET (ARTICLE 19)
54
PCT/US2017/052516 2016-09-21 2017-09-20 Methods and compositions for stimulation and enhancement of regeneration of tissues WO2018057624A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
CA3037712A CA3037712A1 (en) 2016-09-21 2017-09-20 Methods and compositions for stimulation and enhancement of regeneration of tissues
EP17853814.6A EP3515450A4 (en) 2016-09-21 2017-09-20 Methods and compositions for stimulation and enhancement of regeneration of tissues
JP2019537034A JP2019529558A (en) 2016-09-21 2017-09-20 Stimulation and promotion of tissue regeneration

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US15/272,098 2016-09-21
US15/272,098 US20170007624A1 (en) 2012-12-20 2016-09-21 Methods and compositions for stimulation and enhancement of regeneration of tissues

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WO2018057624A4 true WO2018057624A4 (en) 2018-05-17

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KR101799214B1 (en) * 2016-12-01 2017-11-20 재단법인 전남생물산업진흥원 Pharmaceutical composition and functional food having anti-depressant activity, and preparation method of the same.
WO2022007894A1 (en) * 2020-07-08 2022-01-13 北京荣祥再生医学研究所有限公司 Method for regulating expression level of musashi1 in cells

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US6596712B2 (en) * 1996-04-26 2003-07-22 Genaera Corporation Treatment of carcinomas using squalamine in combination with other anti-cancer agents or modalities
JP2002522501A (en) * 1998-08-12 2002-07-23 ジェネーラ・コーポレーション Aminosterol compounds and their uses
CN1827766B (en) * 2001-06-28 2010-08-25 徐荣祥 In vitro cell cultivation method
JP4750697B2 (en) * 2003-06-25 2011-08-17 オタワ ヘルス リサーチ インスティテュート Methods and compositions for regulating stem cell growth and differentiation
US8852938B2 (en) * 2006-11-01 2014-10-07 Rutgers, The State University Of New Jersey Lithium stimulation of cord blood stem cell proliferation and growth factor production
WO2010011185A1 (en) * 2008-07-21 2010-01-28 Agency For Science, Technology And Research Stem cells obtained through in vitro culture with heparan sulfate
EP2934543B1 (en) * 2012-12-20 2018-10-31 Mount Desert Island Biological Laboratory Stimulation and enhancement of regeneration of tissues
US20170007624A1 (en) * 2012-12-20 2017-01-12 Mount Desert Island Biological Laboratory Methods and compositions for stimulation and enhancement of regeneration of tissues

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WO2018057624A1 (en) 2018-03-29
CA3037712A1 (en) 2018-03-29
EP3515450A1 (en) 2019-07-31
JP2019529558A (en) 2019-10-17
EP3515450A4 (en) 2020-07-29

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