US20090042833A1 - Pharmaceutical formulation for the treatment of osteoarthritis containing clodronic acid and hyaluronic acid - Google Patents
Pharmaceutical formulation for the treatment of osteoarthritis containing clodronic acid and hyaluronic acid Download PDFInfo
- Publication number
- US20090042833A1 US20090042833A1 US12/159,222 US15922206A US2009042833A1 US 20090042833 A1 US20090042833 A1 US 20090042833A1 US 15922206 A US15922206 A US 15922206A US 2009042833 A1 US2009042833 A1 US 2009042833A1
- Authority
- US
- United States
- Prior art keywords
- hyaluronic acid
- compositions
- acid
- salts
- treatment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
- A61K31/663—Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- 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
Definitions
- This invention relates to pharmaceutical formulations containing hyaluronic acid and clodronic acid or their salts, especially their sodium salts, as active constituents.
- Osteoarthritis is a progressive chronic illness which particularly affects the joints most subject to mechanical stresses, such as the hips and knees. When this condition arises, the whole joint is affected by a series of degradation and repair processes which eventually alter the anatomy and function of the joint, affecting all the joint components such as the cartilage, subchondral bone and synovial tissues. OA is therefore the result of a set of interrelations between systemic factors (e.g. advanced age or obesity) and local factors (e.g. trauma or excessive use) which are modulated in turn by numerous predisposing factors, possibly combined with infectious and inflammatory events with various aetiologies. In the past, the cartilage was considered to be responsible for OA, and its only target. However, extensive evidence has recently been obtained that the subchondral bone may be the pathogenetic factor responsible for the onset and progress of OA.
- systemic factors e.g. advanced age or obesity
- local factors e.g. trauma or excessive use
- bisphosphonates are well known substances for inhibiting bone resorption and are used in the treatment of postmenopausal osteoporosis, Paget's disease, and tumour osteolysis.
- sodium clodronate which belongs to the category of bisphosphonates, proved able to inhibit damaging effects on the joint structures by Freund's adjuvant, which suggests a possible use in joint disease, especially gonarthritis and coxarthritis, in view of its effects on the inflammatory cytokines, its inhibiting effect on the macrophages and the production of metalloproteases, and its stabilising effect on the subchondral bone.
- clodronate treatment determined a significant improvement of patient's symptomatology (R. Cocco et al.—J. Biol. Res., 1999 September N. 11-12-Vol LXXV) suggesting a possible role of bisphosphonate in the treatment of osteoarthritis.
- EP 0203649 discloses the use of clodronic acid at the concentration from 10 ⁇ 1 to 10 ⁇ 6 M for the preparation of a medicament to be administered intra-articularly for the treatment of osteoarthritis.
- Hyaluronan products include Hyalgan® (sodium hyaluronate, molecular weight [MW] 500-730 kDa), Supartz® (sodium hyaluronate, MW 630-1170 kDa), Artz® (sodium hyaluronate, MW 700- 1,200 kDa) and others of higher molecular weight (MW from 1100 to 6000 kDa) such as Orthovisc® (MW 1100-2900), Nuflexxa® (MW 2400-3500 kDa) and Synviscg (hylan G-F 20, approx MW 6000 kDa).
- Hyalgan® sodium hyaluronate, molecular weight [MW] 500-730 kDa
- Supartz® sodium hyaluronate, MW 630-1170 kDa
- Artz® sodium hyaluronate, MW 700- 1,200 kDa
- others of higher molecular weight MW
- Sodium hyaluronate (MW 500-730 kDa) is administered as three or five weekly 2ml, 10 mg/ml injections ( Hyalgan—Prescribing Information. NY Sanofi - Synthelabo Inc. 2001); similarly sodium hyaluronate (MW 630-1170 kDa; 700-1200 kDa) is administered as a weekly 2.5 ml, 10 mg/ml injection for 5 weeks ( Supartz—package insert; Seikagaku Corporation 2001; Artz—Prescribing Information ) and higher molecular weight hyaluronans are employed as at least three to five weekly 2 ml, from 8 to 25 mg/ml (M. Pagnano, G. Westrich; Osteoarthritis and Cartilage (2005), 13, 751-761; L. Stefan et al. Ann Rheum Dis, 1996, 55:424-431).
- hyaluronic acid involves not only some interference with the synovial cells, but also a mechanical effect of lubrication of the cartilage structures. Its efficacy in the relief of pain and improvement in joint function has been shown in numerous clinical studies.
- oligosaccharide fragments of hyaluronic acid deriving from the degradation activity of the endogenous enzyme hyaluronidase also posses an angiogenetic action as well as stimulating the production of proinflammatory cytokines (TNF ⁇ and IL-1 ⁇ ) by the macrophages (M. Fiorini et al.—Rivista Italiana di Tissue Banking 51-52; D. C West et al.—Science 1985, 228:1324-1326; A. Sattar et al.—J. Invest Dermatol, 1994, 103:576-9), events which can occur after the intra-articular application of hyaluronic acid and that can certainly be harmful to a cartilage if not suitably counteracted.
- the present formulation thanks to the buffered and masking effect of hyaluronic acid, permits the administration of clodronate thus reducing the pain commonly related to intra-articular administration.
- the formulations of invention therefore surprisingly represent a new improved solution for the treatment of OA which is particularly advantageous in terms of efficacy, compliance and reduction of adverse effects compared with the prior art.
- the object of the present invention is a pharmaceutical composition
- clodronic acid and hyaluronic acid or their salts as active ingredients.
- the sodium clodronate concentration can range between 0.5 mg and approx. 1.5-2.0 mg.
- the preferred concentration is 1 mg/ampoule in 1 or 2 ml of hyaluronic acid.
- Higher doses of clodronate (approx 3-5 mg) can be used, provided that they are suitably buffered with appropriate amounts of hyaluronic acid. Said amounts can reasonably range between 5 and 30 mg/ampoule and final volumes of between 0.5 and 5.0 ml, to be used according to the joint affected.
- Hyaluronic acid in all its different forms with different molecular weights (MW from 0.4 ⁇ 10 3 kDa to approx 6 ⁇ 10 3 kDa) as known from the present prior art or which could be developed in the future can be used to perform the present invention.
- Preferred hyaluronic acids or sodium salt thereof are those with a molecular weight (MW) of between 0.4 and 1.5 ⁇ 10 3 kDa.
- Sodium clodronate and sodium hyaluronan solutions generally have a pH of between 4.8 and 6.0.
- a preferred solution of the invention consists in a composition of 1 mg of sodium clodronate in 1 or 2 ml of hyaluronic acid sodium salt, with a molecular weight of approx 0.6 ⁇ 10 3 kDa (10-20 mg).
- a further preferred solution of the invention consists in a composition of 3 mg of sodium clodronate in 2-3 ml of hyaluronic acid sodium salt, with a molecular weight of approx 0.9 ⁇ 10 3 kDa (25 mg).
- compositions according to the invention may contain the usual preservatives, especially for the formulation of the combined product in disposable syringes.
- the invention therefore improved efficacy as measured by both Womac 20 and Womac 50.
- composition of the present invention resolves the symptomatology of a major number of patients, but three weekly administrations are enough to give better results than cycles of five weekly infiltrations of the two substances administered separately.
- the composition of the invention resolves the patient's symptomatology also in a shorter time than the two active principles given separately.
- composition of the invention gives better response in term of time and number of responders by means a total reduced quantity of each single drug (60 mg of sodium hyaluronate towards 100 mg of the same, and 3 mg of clodronic acid towards 5 mg of the same).
- the tolerability of the combined treatment was excellent; in particular, no cases of acute microcrystalline arthritis or knee pain were observed in the hours following the injection.
- composition of the invention in another experimental analysis two patients suffering from severe gonarthritis , as assessed by radiological analysis, received an infiltration of a high clodronic acid concentration (3 mg) together with sodium hyaluronate (Artz) 25 mg/2.5 ml.
- the patients reported a reduced symptomatology in terms of VAS (pain visual analogue scale; Elsevier 1984—Oxford University Press; 1989) 7 days after the treatment, and also no pain response at the time of the injection which instead normally occurs when clodronate alone is administered intra-articularly, especially at high concentration.
- VAS pain visual analogue scale
- the composition of the invention thanks to the presence of hyaluronic acid, also allows to administer high concentration of clodronate in patients in need thereof.
- composition of the present invention represents an improved solution in terms of efficacy and compliance for the treatment of osteoarthritis (OA). Furthermore, it constitutes a new possible approach of treatment especially for those patients in which separate treatments failed.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Biomedical Technology (AREA)
- Vascular Medicine (AREA)
- Anesthesiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT002515A ITMI20052515A1 (it) | 2005-12-29 | 2005-12-29 | Formulazione farmaceutica per il trattamento della osteoartrite |
ITMI2005A002515 | 2005-12-29 | ||
PCT/EP2006/012367 WO2007073921A1 (en) | 2005-12-29 | 2006-12-21 | Pharmaceutical formulation for the treatment of osteoarthritis containing clodronic acid and hyaluronic acid |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2006/012367 A-371-Of-International WO2007073921A1 (en) | 2005-12-29 | 2006-12-21 | Pharmaceutical formulation for the treatment of osteoarthritis containing clodronic acid and hyaluronic acid |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US14/476,521 Continuation US9943540B2 (en) | 2005-12-29 | 2014-09-03 | Pharmaceutical formulation for the treatment of osteoarthritis containing clodronic acid and hyaluronic acid |
Publications (1)
Publication Number | Publication Date |
---|---|
US20090042833A1 true US20090042833A1 (en) | 2009-02-12 |
Family
ID=36648609
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/159,222 Abandoned US20090042833A1 (en) | 2005-12-29 | 2006-12-21 | Pharmaceutical formulation for the treatment of osteoarthritis containing clodronic acid and hyaluronic acid |
US14/476,521 Active US9943540B2 (en) | 2005-12-29 | 2014-09-03 | Pharmaceutical formulation for the treatment of osteoarthritis containing clodronic acid and hyaluronic acid |
US15/907,300 Abandoned US20180185407A1 (en) | 2005-12-29 | 2018-02-28 | Pharmaceutical formulation for the treatment of osteoarthritis containing clodronic acid and hyaluronic acid |
US16/728,378 Abandoned US20200147126A1 (en) | 2005-12-29 | 2019-12-27 | Pharmaceutical formulation for the treatment of osteoarthritis containing clodronic acid and hyaluronic acid |
Family Applications After (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US14/476,521 Active US9943540B2 (en) | 2005-12-29 | 2014-09-03 | Pharmaceutical formulation for the treatment of osteoarthritis containing clodronic acid and hyaluronic acid |
US15/907,300 Abandoned US20180185407A1 (en) | 2005-12-29 | 2018-02-28 | Pharmaceutical formulation for the treatment of osteoarthritis containing clodronic acid and hyaluronic acid |
US16/728,378 Abandoned US20200147126A1 (en) | 2005-12-29 | 2019-12-27 | Pharmaceutical formulation for the treatment of osteoarthritis containing clodronic acid and hyaluronic acid |
Country Status (21)
Country | Link |
---|---|
US (4) | US20090042833A1 (ko) |
EP (1) | EP1976538B1 (ko) |
JP (1) | JP2009522218A (ko) |
KR (2) | KR20140107651A (ko) |
AT (1) | ATE446763T1 (ko) |
AU (1) | AU2006331019B2 (ko) |
CA (1) | CA2646974C (ko) |
CY (1) | CY1109541T1 (ko) |
DE (1) | DE602006010111D1 (ko) |
DK (1) | DK1976538T3 (ko) |
ES (1) | ES2333615T3 (ko) |
HK (1) | HK1123986A1 (ko) |
IT (1) | ITMI20052515A1 (ko) |
NO (1) | NO340794B1 (ko) |
NZ (1) | NZ569420A (ko) |
PL (1) | PL1976538T3 (ko) |
PT (1) | PT1976538E (ko) |
RU (1) | RU2414908C2 (ko) |
SI (1) | SI1976538T1 (ko) |
WO (1) | WO2007073921A1 (ko) |
ZA (1) | ZA200805598B (ko) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6091415B2 (ja) * | 2010-10-07 | 2017-03-08 | ナショナル チェン クン ユニバーシティー | 糖尿病における虚血肢の血流の促進のためのヒアルロナンの使用 |
CN118161444A (zh) | 2014-11-07 | 2024-06-11 | 胞外体干细胞株式会社 | 用于成脂分化诱导、脂肪组织再生、皮肤美白或改善皱纹的包含干细胞来源外泌体的组合物 |
KR101706642B1 (ko) | 2015-02-04 | 2017-02-17 | 주식회사 엑소스템텍 | 연골세포로 분화되고 있는 줄기세포로부터 추출된 엑소좀을 포함하는 연골세포 분화 유도 또는 연골조직 재생용 조성물 |
IT201600123773A1 (it) | 2016-12-06 | 2018-06-06 | Abiogen Pharma Spa | Composizione per il trattamento dell’osteoartrosi |
IT202100023894A1 (it) * | 2021-09-16 | 2023-03-16 | Professional Derma Sa | Composizione per utilizzo in campo ortopedico |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6676970B2 (en) * | 1922-05-05 | 2004-01-13 | Hoffman-La Roche Inc. | Subcutaneous osteoporosis compositions |
WO2005105058A1 (en) * | 2004-05-04 | 2005-11-10 | Amorepacific Corporation | Sustained-releasing injectable formulation for the treatment or prevention of bone-related diseases comprising bisphorenate-containing polymeric microparticles |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1187828B (it) | 1985-05-24 | 1987-12-23 | Gentili Ist Spa | Composizione farmaceutica a base di difosfonati per il trattamento dell aretrosi |
JP2001253827A (ja) * | 2000-02-15 | 2001-09-18 | Pfizer Prod Inc | 骨粗鬆症を治療するための組成物および方法 |
NZ536478A (en) * | 2002-05-17 | 2008-02-29 | Wyeth Corp | Injectable or implantable solid, rod- shaped compositions for intraosseous delivery of osteogenic proteins |
-
2005
- 2005-12-29 IT IT002515A patent/ITMI20052515A1/it unknown
-
2006
- 2006-12-21 EP EP06841087A patent/EP1976538B1/en active Active
- 2006-12-21 JP JP2008547886A patent/JP2009522218A/ja active Pending
- 2006-12-21 CA CA2646974A patent/CA2646974C/en active Active
- 2006-12-21 ZA ZA200805598A patent/ZA200805598B/xx unknown
- 2006-12-21 PL PL06841087T patent/PL1976538T3/pl unknown
- 2006-12-21 SI SI200630473T patent/SI1976538T1/sl unknown
- 2006-12-21 DK DK06841087T patent/DK1976538T3/da active
- 2006-12-21 AU AU2006331019A patent/AU2006331019B2/en active Active
- 2006-12-21 PT PT06841087T patent/PT1976538E/pt unknown
- 2006-12-21 US US12/159,222 patent/US20090042833A1/en not_active Abandoned
- 2006-12-21 ES ES06841087T patent/ES2333615T3/es active Active
- 2006-12-21 AT AT06841087T patent/ATE446763T1/de active
- 2006-12-21 NZ NZ569420A patent/NZ569420A/en unknown
- 2006-12-21 DE DE602006010111T patent/DE602006010111D1/de active Active
- 2006-12-21 WO PCT/EP2006/012367 patent/WO2007073921A1/en active Application Filing
- 2006-12-21 KR KR1020147021224A patent/KR20140107651A/ko active IP Right Grant
- 2006-12-21 RU RU2008126108/15A patent/RU2414908C2/ru active
-
2008
- 2008-06-26 KR KR1020087015583A patent/KR101470608B1/ko active IP Right Grant
- 2008-06-26 NO NO20082848A patent/NO340794B1/no unknown
-
2009
- 2009-04-03 HK HK09103213.6A patent/HK1123986A1/xx unknown
- 2009-12-03 CY CY20091101271T patent/CY1109541T1/el unknown
-
2014
- 2014-09-03 US US14/476,521 patent/US9943540B2/en active Active
-
2018
- 2018-02-28 US US15/907,300 patent/US20180185407A1/en not_active Abandoned
-
2019
- 2019-12-27 US US16/728,378 patent/US20200147126A1/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6676970B2 (en) * | 1922-05-05 | 2004-01-13 | Hoffman-La Roche Inc. | Subcutaneous osteoporosis compositions |
WO2005105058A1 (en) * | 2004-05-04 | 2005-11-10 | Amorepacific Corporation | Sustained-releasing injectable formulation for the treatment or prevention of bone-related diseases comprising bisphorenate-containing polymeric microparticles |
Non-Patent Citations (5)
Title |
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"Dispersion", Wikipedia, also available at "http://en.wikipedia.org/wiki/Dispersion_(chemistry)"; viewed 27 February 2014. * |
Filipponi, P. et al., Bone, "Intermittent Versus Continuous Clodronate Administration in Postmenopausal Women With Low Bone Mass", 2000, vol. 26, no. 3, pp.269-274 * |
Kinne, R. W. et al., Arthritis & Rheumatism, "Long-Term Amelioration of Rat Adjuvant Arthritis Following Systemic Elimination of Macrophages by Clodronate-Containing Liposomes", 1995, vol. 38, no. 12, pp.1777-1790 * |
Pearlgood, M. et al., The Journal of the Royal College of General Practitioners, "Intra-articular corticosteroid therapy in general practice", 1971, vol. 21, pp.410-413 * |
Vemula, V. R. et al., International Journal of Pharmaceutical Sciences Review and Research, "Solubility Enhancement Techniques", November-December 2010, vol. 5, no.1, pp.41-51 * |
Also Published As
Publication number | Publication date |
---|---|
CA2646974C (en) | 2013-06-11 |
AU2006331019A2 (en) | 2009-01-22 |
KR101470608B1 (ko) | 2014-12-09 |
RU2008126108A (ru) | 2010-01-10 |
ES2333615T3 (es) | 2010-02-24 |
KR20140107651A (ko) | 2014-09-04 |
US20200147126A1 (en) | 2020-05-14 |
NO340794B1 (no) | 2017-06-19 |
US20140371170A1 (en) | 2014-12-18 |
US20180185407A1 (en) | 2018-07-05 |
PT1976538E (pt) | 2009-12-07 |
AU2006331019A1 (en) | 2007-07-05 |
ITMI20052515A1 (it) | 2007-06-30 |
DK1976538T3 (da) | 2010-01-11 |
ZA200805598B (en) | 2009-11-25 |
CY1109541T1 (el) | 2014-08-13 |
AU2006331019B2 (en) | 2012-03-22 |
NO20082848L (no) | 2008-08-27 |
PL1976538T3 (pl) | 2010-03-31 |
HK1123986A1 (en) | 2009-07-03 |
KR20080082657A (ko) | 2008-09-11 |
CA2646974A1 (en) | 2007-07-05 |
RU2414908C2 (ru) | 2011-03-27 |
JP2009522218A (ja) | 2009-06-11 |
WO2007073921A1 (en) | 2007-07-05 |
EP1976538A1 (en) | 2008-10-08 |
NZ569420A (en) | 2010-05-28 |
ATE446763T1 (de) | 2009-11-15 |
SI1976538T1 (sl) | 2010-01-29 |
EP1976538B1 (en) | 2009-10-28 |
US9943540B2 (en) | 2018-04-17 |
DE602006010111D1 (de) | 2009-12-10 |
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Owner name: ABIOGEN PHARMA S.P.A., ITALY Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:ROSINI, SERGIO;TRASCIATTI, SILVIA;REEL/FRAME:021153/0381 Effective date: 20080606 |
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