WO1995011697A1 - Accelerateur de guerison utilise en chondroplastie - Google Patents
Accelerateur de guerison utilise en chondroplastie Download PDFInfo
- Publication number
- WO1995011697A1 WO1995011697A1 PCT/JP1994/001803 JP9401803W WO9511697A1 WO 1995011697 A1 WO1995011697 A1 WO 1995011697A1 JP 9401803 W JP9401803 W JP 9401803W WO 9511697 A1 WO9511697 A1 WO 9511697A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- pth
- cartilage
- bone
- human
- parathyroid hormone
- Prior art date
Links
- 239000000199 parathyroid hormone Substances 0.000 claims abstract description 50
- 102000003982 Parathyroid hormone Human genes 0.000 claims abstract description 48
- 108090000445 Parathyroid hormone Proteins 0.000 claims abstract description 48
- 229960001319 parathyroid hormone Drugs 0.000 claims abstract description 48
- 239000004480 active ingredient Substances 0.000 claims abstract description 5
- 210000000845 cartilage Anatomy 0.000 claims description 46
- 230000009467 reduction Effects 0.000 claims description 23
- 238000001356 surgical procedure Methods 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 11
- 229940124597 therapeutic agent Drugs 0.000 claims description 5
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- 101001135770 Homo sapiens Parathyroid hormone Proteins 0.000 claims description 3
- 101001135995 Homo sapiens Probable peptidyl-tRNA hydrolase Proteins 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 102000058004 human PTH Human genes 0.000 claims description 3
- 230000001737 promoting effect Effects 0.000 claims description 3
- 238000002271 resection Methods 0.000 claims description 2
- OGBMKVWORPGQRR-UMXFMPSGSA-N teriparatide Chemical group C([C@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)[C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CNC=N1 OGBMKVWORPGQRR-UMXFMPSGSA-N 0.000 claims 2
- 210000000988 bone and bone Anatomy 0.000 description 13
- 230000008439 repair process Effects 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 11
- 210000005065 subchondral bone plate Anatomy 0.000 description 9
- 210000001188 articular cartilage Anatomy 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 108090000765 processed proteins & peptides Proteins 0.000 description 8
- 210000001612 chondrocyte Anatomy 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000008929 regeneration Effects 0.000 description 6
- 238000011069 regeneration method Methods 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 4
- 230000007547 defect Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000035876 healing Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 230000002980 postoperative effect Effects 0.000 description 4
- 210000000689 upper leg Anatomy 0.000 description 4
- 241000272875 Ardeidae Species 0.000 description 3
- 101000958041 Homo sapiens Musculin Proteins 0.000 description 3
- 230000032683 aging Effects 0.000 description 3
- 230000010478 bone regeneration Effects 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 3
- 102000046949 human MSC Human genes 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 206010061762 Chondropathy Diseases 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 206010017076 Fracture Diseases 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 208000024429 articular cartilage disease Diseases 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000002308 calcification Effects 0.000 description 2
- 208000015100 cartilage disease Diseases 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000003412 degenerative effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000005553 drilling Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 210000004349 growth plate Anatomy 0.000 description 2
- 230000001338 necrotic effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 208000006820 Arthralgia Diseases 0.000 description 1
- 206010068975 Bone atrophy Diseases 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- 206010023201 Joint contracture Diseases 0.000 description 1
- 206010023230 Joint stiffness Diseases 0.000 description 1
- 102000055008 Matrilin Proteins Human genes 0.000 description 1
- 108010072582 Matrilin Proteins Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 101100518501 Mus musculus Spp1 gene Proteins 0.000 description 1
- 208000002565 Open Fractures Diseases 0.000 description 1
- 241000906034 Orthops Species 0.000 description 1
- 206010031252 Osteomyelitis Diseases 0.000 description 1
- 206010031264 Osteonecrosis Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 201000007327 bone benign neoplasm Diseases 0.000 description 1
- 210000002449 bone cell Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 230000004097 bone metabolism Effects 0.000 description 1
- 230000008416 bone turnover Effects 0.000 description 1
- 238000001804 debridement Methods 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 210000002745 epiphysis Anatomy 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 210000001621 ilium bone Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 208000008798 osteoma Diseases 0.000 description 1
- 230000000803 paradoxical effect Effects 0.000 description 1
- 210000002990 parathyroid gland Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000009645 skeletal growth Effects 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/29—Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/635—Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
Definitions
- the present invention relates to a therapeutic accelerator in cartilage reduction. More particularly, the present invention relates to a drug that promotes healing, ie, bone regeneration and cartilage repair, in cartilage reduction surgery in which a defect is formed in the subchondral bone and articular cartilage.
- Articular cartilage has a role as a cushion against loads and impacts, and is also important as guaranteeing mobility in joints.However, even with the same cartilage, growth plate cartilage plays an important role in skeletal growth. Be distinguished. In other words, the growth plate and bone cells present at the epiphysis and other parts achieve their physiological significance by proliferating and differentiating and then calcifying and replacing bone, whereas calcification is a desired function in articular cartilage. Contrary to this and usually does not cause calcification. This is why articular cartilage is called permanent or stationary cartilage.
- Articular cartilage disorders can occur for a variety of reasons. These include joint overuse, joint trauma, fractures, infection, chronic arthritis, endocrine abnormalities, and metabolic abnormalities. It is often thought to be closely related to aging and aging, for which the cause cannot be identified.
- This joint condition which is collectively called osteoarthritis and is based on the degenerative degeneration of joint components centered on articular cartilage, has become a serious social problem due to the aging society and the number of patients is growing rapidly. ing.
- cartilage matrix destruction progresses, the cartilage layer becomes thinner, and subchondral bone hardens in the load area, which further increases the stress on cartilage, and further degenerates and destroys cartilage. Go.
- the cartilage layer is completely lost locally, and the subchondral bone is exposed, and is worn and dentinized by frictional motion.
- cartilage reduction procedures include arthroscopic perforation by drilling the affected area where the cartilage layer is damaged, recurrence to the subchondral bone, and removal of necrotic tissue.
- Chen Yongzhen, Joint Surgery, 8, 113-121 (1989) Ch i 1 der, El ll wo o ⁇ C lin. O rt ho p.. 144, 114—120 (1979)) performed perforation in patients with extra-knee cartilage disorders, and Good results have been obtained.
- S workede et al. (Clin. Orthop., 144, 74—83 (1979)) reported that degenerative arthritic knees were subjected to debridement and resection in 73% of patients. I see joint stiffness and pain relief.
- Surgery to create defects in the bone for surgical treatment includes, for example, benign bone tumors and osteomas, when harvesting bone grafts (eg, iliac bones), joint contractures, open fractures, complex fractures, bone atrophy, It is performed due to osteonecrosis, osteomyelitis, etc., and cartilage reduction can be considered as a surgical technique in which the surgical site is limited to the joint.
- bone grafts eg, iliac bones
- joint contractures eg, open fractures, complex fractures, bone atrophy
- cartilage reduction can be considered as a surgical technique in which the surgical site is limited to the joint.
- the present inventors have continued research on drugs that promote bone regeneration and cartilage repair in surgical cartilage reduction, and as a result, parathyroid hormone ( ⁇ ⁇ ⁇ ⁇ ) showed such a useful effect.
- PTH is the most important hormone involved in bone metabolism secreted by the parathyroid gland, its pharmacological effects are diverse. In short, its effect is to promote bone turnover, and in recent years, in addition to the long-known activity of promoting bone absorption, bone formation has also attracted attention, and its potential as a therapeutic agent for osteoporosis is being investigated. .
- the present inventors suggest that PTH promotes the differentiation of various undifferentiated cells derived from blood in surgical cartilage reduction with hemorrhage, repairs bone defects, and helps regeneration of cartilage tissue.
- Animal experiments were performed based on the hypothesis. In other words, when repairing a hole drilled from the surface of the cartilage at the distal end of the egret femur, the subchondral bone grew faster in the PTH-administered group than in the control group, and the cartilage layer was almost normal in regeneration. Was found to be fast.
- Fig. 1 is a photograph of the HE-stained tissue specimen at the 21st postoperative day in the PTH administration group.
- FIG. 2 is a photograph of the HE-stained tissue specimen of the control group 21 days after the operation.
- FIG. 3 is a photograph of the HE-stained tissue specimen of the control group on day 42 after the operation.
- Figure 4 is a photograph of the 21st post-operative Alshan blue stained tissue specimen in the PTH-administered group.
- FIG. 5 is a photograph of the 21st post-operative Alshan blue stained tissue specimen of the control group.
- FIG. 6 is a photograph of the Alshambre single-stained tissue specimen of the control group on day 42 after the operation.
- the parathyroid hormone (PTH) in the present invention includes natural PTH, PTH produced by a genetic method, and PTH chemically synthesized, and preferably comprises human PTH comprising 84 amino acid residues.
- the PTH derivative means a peptide having the same activity as the above-mentioned partial peptide of PTH or a peptide in which the amino acid constituting PTH itself or its partial peptide is partially replaced with another amino acid.
- Examples of the partial peptide of PTH include, for example, human 1-34PTH and peptide 1-34PTH.
- 1-34 PTH means the partial peptide of PTH consisting of 34 amino acids from the N-terminal to the 34th amino acid of PTH.
- Parathyroid hormone used as a therapeutic accelerator in bone reduction according to the present invention is used as a therapeutic accelerator in bone reduction according to the present invention.
- Preferred examples of (PTH) or PTH derivatives human 1-84PTH, human 1 one 34PTH, human 1 one 38PTH, human 1 one 37 PTH, such as human 1-34P TH- NH 2 and the like, More preferred are human 1-84 PTH and human 1-34 PTH, and most preferred is human 1-84 PTH.
- Cartilage repair such as drilling a hole in the affected area where the cartilage layer is damaged under arthroscopic vision, recurrence to the subchondral bone, and removal of necrotic tissue. It means the intended surgical treatment of cartilage and subchondral bone.
- the dosage form of the drug of the present invention in addition to an injection prepared by a usual preparation method of a peptide, localization and delayed action such as encapsulation in a microcapsule or inclusion in a gel sheet were expected. Dosage forms are also possible. In the case of a liquid preparation, it is preferable to add an appropriate protein or an appropriate anti-adhesion agent.
- the method of administering the agent of the present invention can be performed by systemic administration or local administration. Preferred examples include whole injection such as local injection into the joint cavity or into a lesion by injection, or subcutaneous administration.
- the dosage of PTH of the present invention, the adaptive diseases, varies depending on such conditions, 10 7 M from 10-15 at the tissue level by topical administration, from 10 to 1000 gZ head is preferable than systemic administration.
- the administration timing may be either before or after cartilage reduction surgery, but administration after surgery is more preferable.
- PTH used in the examples was prepared by using a modified method of the method described in Japanese Patent Publication No. 505259/1992 and J. Biol. Chem., 265, 15854 (1990).
- the following experiment was performed as an experiment using an animal model of cartilage reduction.
- JWZCSK Japanese White Heron
- the darkly stained portion with HE staining in Fig. 1, Fig. 2 and Fig. 3 is the bone (subchondral bone), and the darkly stained portion with Alshan blue staining in Fig. 4, Fig. 5 and Fig. 6.
- the repair of the hole drilled from the ⁇ distal end of the heron's femur ⁇ bone surface was performed in the PTH-administered group not only at the same time as the control group (21 after surgery) but also in the control group. 42 Compared to 42 days after the operation, ⁇ the growth of the subosseous bone was faster, near normal, and the regeneration of the cartilage layer was much faster '.
- the drug containing the PTH or PTH derivative of the present invention as an active ingredient is useful for promoting healing in surgical cartilage reduction surgery.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Endocrinology (AREA)
- Chemical & Material Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Toxicology (AREA)
- Immunology (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU80029/94A AU8002994A (en) | 1993-10-27 | 1994-10-27 | Cure accelerator in chondroplasty |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5/303204 | 1993-10-27 | ||
| JP30320493 | 1993-10-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1995011697A1 true WO1995011697A1 (fr) | 1995-05-04 |
Family
ID=17918138
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP1994/001803 WO1995011697A1 (fr) | 1993-10-27 | 1994-10-27 | Accelerateur de guerison utilise en chondroplastie |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU8002994A (de) |
| TW (1) | TW273513B (de) |
| WO (1) | WO1995011697A1 (de) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998024471A1 (en) * | 1996-12-05 | 1998-06-11 | Société De Conseils De Recherches Et D'applications Scientifiques S.A.; | Treatment of bone fracture |
| WO1999012561A2 (en) * | 1997-09-09 | 1999-03-18 | F. Hoffman-La Roche Ag | FRACTURE HEALING USING PTHrP ANALOGS |
| EP0811383A4 (de) * | 1995-02-20 | 2000-02-09 | Yukio Kato | Heilmittel für arthrosis deformans und entzündliche gelenkerkrankungen |
| WO2010045229A2 (en) | 2008-10-13 | 2010-04-22 | University Of Rochester | Protecting and repairing cartilage and musculoskeletal soft tissues |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0532696A (ja) * | 1990-09-28 | 1993-02-09 | Takeda Chem Ind Ltd | 副甲状腺ホルモン誘導体 |
| JPH05320193A (ja) * | 1992-03-19 | 1993-12-03 | Takeda Chem Ind Ltd | 副甲状腺ホルモン誘導体 |
| JPH0687897A (ja) * | 1991-05-23 | 1994-03-29 | Allelix Biopharmaceut Inc | 本質的に純粋なヒト副甲状腺ホルモン |
| JPH06184198A (ja) * | 1992-07-15 | 1994-07-05 | Sandoz Ag | ペプチド類 |
-
1994
- 1994-10-27 AU AU80029/94A patent/AU8002994A/en not_active Abandoned
- 1994-10-27 WO PCT/JP1994/001803 patent/WO1995011697A1/ja active Application Filing
- 1994-10-27 TW TW83109910A patent/TW273513B/zh active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0532696A (ja) * | 1990-09-28 | 1993-02-09 | Takeda Chem Ind Ltd | 副甲状腺ホルモン誘導体 |
| JPH0687897A (ja) * | 1991-05-23 | 1994-03-29 | Allelix Biopharmaceut Inc | 本質的に純粋なヒト副甲状腺ホルモン |
| JPH05320193A (ja) * | 1992-03-19 | 1993-12-03 | Takeda Chem Ind Ltd | 副甲状腺ホルモン誘導体 |
| JPH06184198A (ja) * | 1992-07-15 | 1994-07-05 | Sandoz Ag | ペプチド類 |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0811383A4 (de) * | 1995-02-20 | 2000-02-09 | Yukio Kato | Heilmittel für arthrosis deformans und entzündliche gelenkerkrankungen |
| WO1998024471A1 (en) * | 1996-12-05 | 1998-06-11 | Société De Conseils De Recherches Et D'applications Scientifiques S.A.; | Treatment of bone fracture |
| WO1999012561A2 (en) * | 1997-09-09 | 1999-03-18 | F. Hoffman-La Roche Ag | FRACTURE HEALING USING PTHrP ANALOGS |
| WO1999012561A3 (en) * | 1997-09-09 | 1999-05-14 | Hoffmann La Roche | FRACTURE HEALING USING PTHrP ANALOGS |
| AU752925B2 (en) * | 1997-09-09 | 2002-10-03 | F. Hoffmann-La Roche Ag | Fracture healing using PTHrP analogs |
| US6583114B2 (en) | 1997-09-09 | 2003-06-24 | Roche Palo Alto Llc | Fracture healing using pthrp analogs |
| WO2010045229A2 (en) | 2008-10-13 | 2010-04-22 | University Of Rochester | Protecting and repairing cartilage and musculoskeletal soft tissues |
| EP2349325A4 (de) * | 2008-10-13 | 2012-08-29 | Univ Rochester | Schutz und reparatur von knorpel und muskuloskeletalen weichgeweben |
| US8513193B2 (en) | 2008-10-13 | 2013-08-20 | University Of Rochester | Protecting and repairing cartilage and musculoskeletal soft tissues |
| US9192653B2 (en) | 2008-10-13 | 2015-11-24 | University Of Rochester | Protecting and repairing cartilage and musculoskeletal soft tissues |
Also Published As
| Publication number | Publication date |
|---|---|
| TW273513B (de) | 1996-04-01 |
| AU8002994A (en) | 1995-05-22 |
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