US20090197807A1 - Sulphated hyaluronic acid for treating degenerative osteoarthritis - Google Patents

Sulphated hyaluronic acid for treating degenerative osteoarthritis Download PDF

Info

Publication number
US20090197807A1
US20090197807A1 US12/302,511 US30251107A US2009197807A1 US 20090197807 A1 US20090197807 A1 US 20090197807A1 US 30251107 A US30251107 A US 30251107A US 2009197807 A1 US2009197807 A1 US 2009197807A1
Authority
US
United States
Prior art keywords
pharmaceutical composition
hyaluronic acid
sulphated
treatment
degenerative osteoarthritis
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
Application number
US12/302,511
Other languages
English (en)
Inventor
Lanfranco Callegaro
Davide Renier
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fidia Farmaceutici SpA
Original Assignee
Fidia Farmaceutici SpA
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Fidia Farmaceutici SpA filed Critical Fidia Farmaceutici SpA
Assigned to FIDIA FARMACEUTICI S.P.A. reassignment FIDIA FARMACEUTICI S.P.A. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: CALLEGARO, LANFRANCO, RENIER, DAVIDE
Publication of US20090197807A1 publication Critical patent/US20090197807A1/en
Abandoned legal-status Critical Current

Links

Images

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
    • A61K31/70—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
    • A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/01—Hydrolysed proteins; Derivatives thereof
    • A61K38/012—Hydrolysed proteins; Derivatives thereof from animals
    • A61K38/014—Hydrolysed proteins; Derivatives thereof from animals from connective tissue peptides, e.g. gelatin, collagen
    • 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
    • A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds
    • 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
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease

Definitions

  • the present invention relates to oral and intra-articular formulations based on sulphated hyaluronic acid which are effective in the treatment of degenerative osteoarthritis.
  • Osteoarthritis is a very common disorder, characterised by progressive degeneration of the joint cartilage which thins and deteriorates following loss of the cellular and extracellular component, and can even disappear entirely.
  • the causes of the disease are only partly clear. They basically seem to involve a series of processes triggered by a mechanical imbalance that affects the entire joint, for example after a trauma or mechanical stress. Inside the cartilage there is a delicate balance between destruction of the exhausted extracellular matrix and formation of intact matrix. All this depends largely on enzymes produced by the chondrocytes, a cellular component of joint matrix. In the event of an excessive or unbalanced load on the joint, an inflammatory situation arises.
  • degenerative osteoarthritis can be defined as a chronic disease which normally occurs after an initial acute stage of inflammation, known as inflammatory osteoarthritis.
  • inflammatory osteoarthritis The presence or absence of an inflammatory state in the joint (caused by cytokines and MMPs together with other substances) distinguishes the acute inflammatory stage of the disease (inflammatory osteoarthritis) from the chronic non-inflammatory stage (degenerative osteoarthritis).
  • Degenerative osteoarthritis does not only occur as the chronic stage of inflammatory osteoarthritis, but also results from physiological aging of the joint cartilage.
  • the integrity of the extracellular matrix is therefore crucial to the survival of the chondrocytes, and consequently essential for healthy cartilage.
  • the cartilage matrix is a three-dimensional structure consisting of collagen molecules and aggregated complexes of proteoglycans, which in turn are formed by
  • HA is a polysaccharide molecule with considerable viscoelastic properties. It is present in the joint cavities as a fundamental component of synovial fluid, where it acts as a lubricant and shock-absorbing agent, and protects the chondrocytes against the action of the inflammatory cytokines (Asari et al., Arch Histol Cytol, 1995, 58:65-76; Brun et al., Osteoarthr Cartil, 2003, 11:208-16; Stove et al., J Orthop Res, 2002, 20:551-5). HA, as such or in derivatised form, has long been used to treat degenerative osteoarthritis, either as a “viscosupplement” or a lubricant.
  • Hyalgan® HA purified from rooster combs according to EP 138572 B1
  • Synvisc® Hylan G-F20, namely HA crosslinked with formaldehyde and divinyl sulphone, as described in U.S. Pat. No. 4,713,448
  • Artz® HA with a MW of between 620 and 1200 KDa
  • the oral treatments according to the prior art involve the administration of sulphated GAGs such as glucosamine sulphate and chondroitin sulphate in association with HA and hydrolysed collagen, in order to promote HA synthesis in the joint cavity, reduce inflammation, and protect the chondrocytes in an osteoarthritic joint (U.S. Pat. No. 6,645,948; U.S. Pat. No. 6,476,005).
  • GAGs such as glucosamine sulphate and chondroitin sulphate
  • HA glucosamine sulphate and chondroitin sulphate
  • HA sulphated as described in the prior art, to which anti-inflammatory, anticoagulant and cell-adhesion-inhibiting effects are attributed.
  • HA-S sulphated hyaluronic acid
  • autoimmune disease rheumatoid arthritis
  • EP 754460 B1 claims the use of HA-S in the parenteral injectable treatment of inflammatory states, including joint rheumatism.
  • the present invention supersedes the prior art because it relates to formulations based on chemically sulphated HA, for oral administration or intra-articular injection, which effectively slow joint degeneration and promote reconstruction of the extracellular matrix in joints affected by chronic degenerative osteoarthritis, which is consequently not at the inflammatory stage (these compositions therefore cannot be used to treat inflammatory osteoarthritis).
  • the present invention relates to formulations based on HA chemically modified by sulphation as described in EP 702699 B1: the Applicant has demonstrated the therapeutic efficacy of HA-S by comparison with a standard treatment based on sulphated glycosaminoglycans in the treatment of osteoarthritic cartilage deficiency, and compared its efficacy with non-sulphated HA to demonstrate the clear pharmacological superiority of HA-S over both GAGs and HA.
  • the present invention relates to formulations based on HA chemically modified by sulphation, which are effective in the (preferably oral) treatment of chronic forms of degenerative osteoarthritis without inflammatory sequelae.
  • the process of degenerative osteoarthritis causes progressive damage to the extracellular matrix in the joint cartilage. This damage is manifested by thinning of the matrix and loss of the chondrocyte component; the process culminates with the total destruction of the joint cartilage.
  • the disorder can be manifested as chronicisation of inflammatory osteoarthritis or represent the physiological development of the joint aging process.
  • the cartilage can be divided into four different zones, from the joint surface to the subchondral bone, namely:
  • This invention demonstrates that the administration of sulphated hyaluronic acid represents a valid therapeutic approach for these purposes because it increases, within the joint, the presence of the material that constitutes the “scaffolding” of the cartilage matrix and, by ensuring its structural integrity, prevents its decellularisation.
  • the formulations of the invention can therefore also be used for the prevention of cartilage damage.
  • HA-S slows degradation and stimulates regeneration of the basic structure of the extracellular matrix to a surprisingly greater extent than other GAGs and non-sulphated HA.
  • the sulphated hyaluronic acid suitable for the purpose of this invention is prepared according to a process described in EP 702699 B1: sulphation is performed with the SO 3 -pyridine complex, and involves the alcoholic hydroxyls present in the polysaccharide chain.
  • the degree of sulphation can range between 0.5 and 3.5 (EP 0940410 B1), and is preferably between 0.5 and 1.5 (the average grade is defined as 1:1 sulphate group to disaccharide group), starting from HA with different molecular weights, ranging from 50.000 to 800.000 D, preferably 100.000 to 230.000 D, using HA produced by extraction, fermentation or technological means.
  • the derivative obtained maintains all the physical characteristics of the starting polymer; in particular, the molecular weight of HA is not changed by the sulphation process, consequently allowing the same viscosity as the starting polysaccharide to be maintained.
  • HA-S produced by fermentation having an average molecular weight of 180/200 KD and an average degree of sulphation of 1, with a reference treatment based on Condral® (galactosaminoglucuronoglycan sulphate, the depolymerised form of chondroitin sulphate) and with a treatment based on HA (with a molecular weight of 180/200 KD) against the untreated control.
  • Condral® galactosaminoglucuronoglycan sulphate, the depolymerised form of chondroitin sulphate
  • the animals were divided into 4 homogenous groups (6 animals per group) and treated orally, 24 hours after surgery, every day for 61 days, with:
  • the animals were killed and examined macroscopically to check for the absence of systemic toxicity.
  • the lateral and medial condyles of the femur with the tibial plate were fixed in formalin buffered to 10% and embedded in paraffin wax.
  • the preparations were then processed, by a method known to one skilled in the art, to obtain sections analysable under the optical microscope after staining with haematoxylin-eosin.
  • the cartilage tissue removed from the medial and lateral femoral condyles was then subjected to semiquantitative histopathological analysis and histomorphometric analysis.
  • parameters relating to degeneration, the structural integrity of the cartilage and the extent of abrasion on the thickness of the cartilage were taken into consideration.
  • Cartilage tissue Group plasma infiltrates plasma infiltrates Control 0 0 HA-S 0 0 HA 0 0 Condral 0 0
  • the total lack of plasma infiltrates in the synovial fluid and the cartilage confirms the complete absence of inflammation in the joint cavity in the controls treated with NaCl and in all the groups studied.
  • FIG. 1 summarises the data collected from the cartilage examination: in the group of animals treated with saline solution (controls), serious degeneration characterised by morphological alteration of the cell component was evident.
  • the situation of the animals treated with Condral® was better; in this case the cartilage degeneration was estimated at 2.8, and was therefore moderate/marked; it is important to note that this result is very similar to that obtained with HA treatment.
  • the cartilage of the animals treated with HA-S was in a much better situation: the level of degradation was slight (1,7). Oral administration of HA-S therefore proved effective in significantly slowing the process of degradation of the cartilage of joints affected by degenerative osteoarthritis.
  • a second, important evaluation relates to analysis of the structural integrity of the cartilage tissue, which is measured, according to recognised standards, in terms of irregularity of the surface and of the cartilage structure ( FIG. 2 ).
  • This graph confirms that treatment with HA-S helps to maintain good structural integrity, to a significant extent compared with the controls, and also compared with Condral® treatment.
  • the group of animals treated with HA-S only presented slight cracks in the transitional cartilage zone, whereas those treated with Condral® presented marked lesions of the radial zone; the finding relating to treatment with HA, which again proved as effective as Condral®, is particularly interesting.
  • FIG. 3 illustrates the depth of the lesion along the entire thickness of the cartilage, the maximum lesion being one which causes exposure of bone tissue following total loss of cartilage.
  • the data illustrate the mean values of the lesions of the lateral and medial condyles; once again it was confirmed that oral treatment with HA-S is more effective than treatment with Condral® or treatment with HA alone in preserving the integrity of the cartilage matrix.
  • HA-S could possibly be associated with other molecules useful to strengthen the extracellular matrix, such as collagen (possibly hydrolysed) or other GAGs, or with other pharmacologically and/or biologically active substances such as growth factors and/or hormones, vitamins (especially vitamins A, C, D, and E, and group B in general), antibiotics and mineral salts (especially calcium, magnesium and selenium salts and other trace elements).
  • growth factors and/or hormones such as growth factors and/or hormones, vitamins (especially vitamins A, C, D, and E, and group B in general), antibiotics and mineral salts (especially calcium, magnesium and selenium salts and other trace elements).
  • HA-S hyaluronic acid derivatives
  • HA-S could possibly be associated with other molecules such as other GAGs or other pharmacologically and/or biologically active substances such as growth factors and/or hormones, vitamins, antibiotics and antivirals.
  • HA-S preparation of the formulations containing HA-S of the invention, for oral and intra-articular administration, are described below by way of example and not of limitation.
  • HA-S can be formulated in all known ways according to the state of the art in association with stabilisers, excipients, preservatives and/or other substance considered useful to obtain the best possible formulation, for the preparation of granulates, suspensions, solutions, capsules and tablets.
  • the HA used in these formulations has an average degree of sulphation of 1, and an average molecular weight of 180/200 KD; the concentration of the Active ingredient ranges between 50 and 400 mg per dose unit.
  • HA-S 400 Excipients Microcrystalline cellulose 65 Corn starch 15.5 Sorbitol 2250 Polyvinylpyrrolidone 47.5 Citric acid 10 Aspartame 32 Orange flavouring 180
  • HAS1, microcrystalline cellulose and corn starch Initially mix the HAS1, microcrystalline cellulose and corn starch. Mix with the binder solution consisting of water and polyvinylpyrrolidone. When the mixture is uniformly moist, granulate through a 2 mm sieve. Dry the granulate, then sieve the dried granulate, forcing it through an 0.8 mm sieve. Mix the granulate powder with sorbitol, citric acid, aspartame and orange flavouring. Fill sachets with the granulate.
  • HA-S grade 1 or 2 having an average molecular weight of 180/200 KD or 500/750 KD, prepared in sterile, pyrogen-free saline solution at the concentration of 1-100 mg/ml, preferably 5-50 mg/ml, and even more preferably 10-20 mg/ml, is preferably used for the injectable intra-articular preparations.
  • the final solution must be sterile and pyrogen-free. It can also be freeze-dried and reconstituted at the time of use.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
US12/302,511 2006-05-31 2007-05-03 Sulphated hyaluronic acid for treating degenerative osteoarthritis Abandoned US20090197807A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
ITPD2006A000219 2006-05-31
IT000219A ITPD20060219A1 (it) 2006-05-31 2006-05-31 Composizioni farmaceutiche contenenti acido ialuronico solfatato nel trattamento dell'osteoartrosi
PCT/EP2007/003920 WO2007137674A1 (en) 2006-05-31 2007-05-03 Sulphated hyaluronic acid for treating degenerative osteoarthritis

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2007/003920 A-371-Of-International WO2007137674A1 (en) 2006-05-31 2007-05-03 Sulphated hyaluronic acid for treating degenerative osteoarthritis

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US13/410,227 Division US8765714B2 (en) 2006-05-31 2012-03-01 Sulphated hyaluronic acid for treating degenerative osteoarthritis

Publications (1)

Publication Number Publication Date
US20090197807A1 true US20090197807A1 (en) 2009-08-06

Family

ID=38353080

Family Applications (3)

Application Number Title Priority Date Filing Date
US12/302,511 Abandoned US20090197807A1 (en) 2006-05-31 2007-05-03 Sulphated hyaluronic acid for treating degenerative osteoarthritis
US13/410,227 Active US8765714B2 (en) 2006-05-31 2012-03-01 Sulphated hyaluronic acid for treating degenerative osteoarthritis
US14/251,318 Expired - Fee Related US9295690B2 (en) 2006-05-31 2014-04-11 Sulphated hyaluronic acid for treating degenerative osteoarthritis

Family Applications After (2)

Application Number Title Priority Date Filing Date
US13/410,227 Active US8765714B2 (en) 2006-05-31 2012-03-01 Sulphated hyaluronic acid for treating degenerative osteoarthritis
US14/251,318 Expired - Fee Related US9295690B2 (en) 2006-05-31 2014-04-11 Sulphated hyaluronic acid for treating degenerative osteoarthritis

Country Status (15)

Country Link
US (3) US20090197807A1 (ko)
EP (2) EP2021078B1 (ko)
JP (1) JP5537933B2 (ko)
KR (1) KR20090014359A (ko)
CN (1) CN101454048B (ko)
AU (1) AU2007268195A1 (ko)
CA (1) CA2653660C (ko)
DK (1) DK2021078T3 (ko)
ES (2) ES2619309T3 (ko)
HK (2) HK1123235A1 (ko)
IT (1) ITPD20060219A1 (ko)
MX (1) MX2008015212A (ko)
PL (2) PL2786782T3 (ko)
SI (2) SI2021078T1 (ko)
WO (1) WO2007137674A1 (ko)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100317616A1 (en) * 2008-04-04 2010-12-16 University Of Utah Research Foundation Alkylated semi-synthetic glycosaminoglycan ethers, and methods of making and using thereof
US20120101059A1 (en) * 2009-05-14 2012-04-26 Fidia Farmaceutici S.P.A. Sulphated hyaluronic acids as regulator agents of the cytokine activity
US20120219554A2 (en) * 2009-05-14 2012-08-30 Fidia Farmaceutici S.P.A. Extracellular yaluronidase from streptomyces koganeiensis
US8343942B2 (en) 2008-04-04 2013-01-01 University Of Utah Research Foundation Methods for treating interstitial cystitis
WO2013009102A2 (ko) * 2011-07-13 2013-01-17 (주)차바이오앤디오스텍 콜라겐, 히알루론산 유도체 및 포유류의 탯줄 유래 줄기세포를 포함하는 연골세포치료제
US20130310437A1 (en) * 2009-12-21 2013-11-21 Professional Dietetics S.R.L. Combination for the treatment of osteoarthritis
US8835405B2 (en) 2011-09-16 2014-09-16 China Medical University Inhibiting arthritis via injection of synergistic combination of hyaluronic acid and vitamin C and/or vitamin E
US9522162B2 (en) 2011-03-23 2016-12-20 University Of Utah Research Foundation Methods for treating or preventing urological inflammation
US11337994B2 (en) 2016-09-15 2022-05-24 University Of Utah Research Foundation In situ gelling compositions for the treatment or prevention of inflammation and tissue damage

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5088864B2 (ja) * 2007-03-16 2012-12-05 オリンパス株式会社 生体組織補填材とその製造方法
WO2009101194A1 (en) * 2008-02-15 2009-08-20 Bone Therapeutics Pharmaceutical composition for use in the treatment and/or the prevention of osteoarticular diseases
IT1393945B1 (it) 2009-04-21 2012-05-17 Fidia Farmaceutici Composizioni comprendenti acido ialuronico, acido ialuronico solfatato, calcio e vitamina d3 nel trattamento delle malattie osteoarticolari e muscoloscheletriche
IT1397246B1 (it) * 2009-05-14 2013-01-04 Fidia Farmaceutici Nuovi medicamenti ad uso topico a base di acido ialuronico solfatato come agente attivante o inibente l'attivita' citochinica
EP2384759A1 (en) * 2010-05-06 2011-11-09 Suomen Punainen Risti Veripalvelu Sulphated hyaluronic acid in combination with G-CSF for use in mobilising blood stem cells
US8546353B2 (en) 2010-05-06 2013-10-01 Glykos Finland Oy Compounds and combinations
ITPD20120098A1 (it) * 2012-03-30 2013-10-01 Fidia Farmaceutici "nuove formulazioni faramaceutiche contenenti condroitin solfato e derivati dell'acido ialuronico"
EA030022B1 (ru) 2012-09-20 2018-06-29 Маккей Мемориал Хоспитал Применение pedf-производных полипептидов для лечения остеоартрита
US20140186306A1 (en) * 2012-09-28 2014-07-03 Paul Ronald Plante Novel ampk agonist compositions and methods of use
WO2014165513A2 (en) * 2013-04-02 2014-10-09 The Regents Of The University Of California Ethylsulfonated hyaluronic acid biopolymers and methods of use thereof
KR101895950B1 (ko) * 2015-12-18 2018-09-06 (주)한국비엠아이 골관절염 치료를 위한 친수화된 설파살라진 및 히알루론산을 포함하는 조성물 및 이의제조방법
EP3423920B1 (en) 2016-03-02 2022-02-09 Bortek Bor Teknolojileri Ve Mekatronik Sanayi Ticaret Anonim Sirketi Therapeutic mixtures for treating osteoarthritis comprising nano hexagonal boron nitride composition
TWI632915B (zh) * 2016-05-31 2018-08-21 大江生醫股份有限公司 用以治療關節炎之醫藥組成物
KR20200031058A (ko) * 2018-09-13 2020-03-23 주식회사 엘지화학 황산화 히알루론산 기반의 하이드로겔 및 이를 포함하는 약제학적 조성물
WO2021133000A1 (ko) * 2019-12-23 2021-07-01 주식회사 엘지화학 항염 또는 항혈관신생용 약제학적 조성물

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5872109A (en) * 1995-02-07 1999-02-16 Shiseido Company, Ltd. Anti-inflammatory agent
US20030060448A1 (en) * 1997-07-28 2003-03-27 Alberto Rivarossa Use of hyaluronic acid derivatives in the preparation of biomaterials with a physical haemostatic and plugging activity and a preventive activity in the formation of adhesions following anastomosis
US6579978B1 (en) * 1997-04-04 2003-06-17 Fidia Farmaceuti S.P.A. Biomaterials comprising N-sulphated hyaluronic acid compounds or derivatives thereof

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2553099B1 (fr) 1983-10-11 1989-09-08 Fidia Spa Fractions d'acide hyaluronique ayant une activite pharmaceutique, procedes pour leur preparation et compositions pharmaceutiques les contenant
US4713448A (en) 1985-03-12 1987-12-15 Biomatrix, Inc. Chemically modified hyaluronic acid preparation and method of recovery thereof from animal tissues
ITPD940054A1 (it) 1994-03-23 1995-09-23 Fidia Advanced Biopolymers Srl Polisaccaridi solfatati
US6645948B2 (en) 1998-03-24 2003-11-11 George D. Petito Nutritional composition for the treatment of connective tissue
US6476005B1 (en) 1998-03-24 2002-11-05 George D. Petito Oral and injectable nutritional composition
IT1302534B1 (it) * 1998-12-21 2000-09-05 Fidia Advanced Biopolymers Srl Composizioni iniettabili, biocompatibili e biodegradabili comprendentialmeno un derivato dell'acido ialuronico, cellule condrogeniche, per
IT1306644B1 (it) 1999-04-08 2001-10-02 Fidia Advanced Biopolymers Srl Strutture tridimensionali comprendenti derivati dell'acido ialuronicoottenibili mediante la tecnica antisolvente supercritico.
US6288043B1 (en) * 1999-06-18 2001-09-11 Orquest, Inc. Injectable hyaluronate-sulfated polysaccharide conjugates
JP2001163789A (ja) * 1999-12-13 2001-06-19 Maruho Co Ltd マトリックスメタロプロテアーゼ阻害用医薬組成物
US6924273B2 (en) * 2000-10-03 2005-08-02 Scott W. Pierce Chondroprotective/restorative compositions and methods of use thereof
DE10053053A1 (de) 2000-10-19 2002-05-16 Knoell Hans Forschung Ev Pharmazeutische Formulierungen zur Hemmung von entzündlichen Arthritiden
US6607745B2 (en) 2001-05-18 2003-08-19 Harry Leneau Ingestion of hyaluronic acid for improved joint function and health
MXPA01011542A (es) 2001-11-13 2003-05-22 Alcon Inc Regeneracion del cartilago articular da°ado por la osteoartritis de grado i y ii, mediante la aplicacion intra-articular de una mezcla de hialuronato de sodio y de condroitin sulfato en un vehiculo de gel.
CN103638040A (zh) * 2002-07-03 2014-03-19 派瑞克科学公司 透明质酸组合物以及使用方法
CZ13928U1 (cs) 2003-10-08 2004-01-20 Cpn Spol. S R.O. Dietetický přípravek pro prevenci a léčbu osteoporózy
ITPD20040053A1 (it) * 2004-02-27 2004-05-27 Fidia Advanced Biopolymers Srl Biomateriali costituiti da derivati dell'acido ialuronico come nuova terapia di cura per la protezione e la la riparazione della cartilagine articolare danneggiata per osteoartrosi

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5872109A (en) * 1995-02-07 1999-02-16 Shiseido Company, Ltd. Anti-inflammatory agent
US6579978B1 (en) * 1997-04-04 2003-06-17 Fidia Farmaceuti S.P.A. Biomaterials comprising N-sulphated hyaluronic acid compounds or derivatives thereof
US6833363B2 (en) * 1997-04-04 2004-12-21 Fidia Farmaceutici S.P.A. N-sulphated hyaluronic acid compounds, derivatives thereof and a process for their preparation
US20030060448A1 (en) * 1997-07-28 2003-03-27 Alberto Rivarossa Use of hyaluronic acid derivatives in the preparation of biomaterials with a physical haemostatic and plugging activity and a preventive activity in the formation of adhesions following anastomosis

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8399430B2 (en) 2008-04-04 2013-03-19 University Of Utah Research Foundation Alkylated semi synthetic glycosaminoglycosan ethers, and methods for making and using thereof
US7855187B1 (en) 2008-04-04 2010-12-21 University Of Utah Research Foundation Alkylated semi-synthetic glycosaminoglycosan ethers, and methods of making and using thereof
US20110082104A1 (en) * 2008-04-04 2011-04-07 University Of Utah Research Foundation Alkylated semi synthetic glycosaminoglycosan ethers, and methods for making and using thereof
US20100317616A1 (en) * 2008-04-04 2010-12-16 University Of Utah Research Foundation Alkylated semi-synthetic glycosaminoglycan ethers, and methods of making and using thereof
US9549945B2 (en) 2008-04-04 2017-01-24 University Of Utah Research Foundation Use of alkylated semi-synthetic glycosaminoglycosan ethers for the treatment of inflammation
US8329673B2 (en) 2008-04-04 2012-12-11 University Of Utah Research Foundation Alkylated semi synthetic glycosaminoglycosan ethers, and methods for making and using thereof
US8343942B2 (en) 2008-04-04 2013-01-01 University Of Utah Research Foundation Methods for treating interstitial cystitis
US9808482B2 (en) * 2009-05-14 2017-11-07 Fidia Farmaceutici S.P.A. Sulphated hyaluronic acids as regulator agents of the cytokine activity
US20120219554A2 (en) * 2009-05-14 2012-08-30 Fidia Farmaceutici S.P.A. Extracellular yaluronidase from streptomyces koganeiensis
US20120101059A1 (en) * 2009-05-14 2012-04-26 Fidia Farmaceutici S.P.A. Sulphated hyaluronic acids as regulator agents of the cytokine activity
US10208300B2 (en) 2009-05-14 2019-02-19 Fidia Farmaceutici S.P.A. Extracellular hyaluronidase from Streptomyces koganeiensis
US10548918B2 (en) 2009-05-14 2020-02-04 Fidia Farmaceutici S.P.A. Sulphated hyaluronic acids as regulator agents of the cytokine activity
US20130310437A1 (en) * 2009-12-21 2013-11-21 Professional Dietetics S.R.L. Combination for the treatment of osteoarthritis
US9040575B2 (en) * 2009-12-21 2015-05-26 Professional Dietetics, S.R.L. Combination for the treatment of osteoarthritis
US9522162B2 (en) 2011-03-23 2016-12-20 University Of Utah Research Foundation Methods for treating or preventing urological inflammation
US10226481B2 (en) 2011-03-23 2019-03-12 University Of Utah Research Foundation Pharmaceutical compositions composed of low molecular weight sulfated hyaluronan
WO2013009102A2 (ko) * 2011-07-13 2013-01-17 (주)차바이오앤디오스텍 콜라겐, 히알루론산 유도체 및 포유류의 탯줄 유래 줄기세포를 포함하는 연골세포치료제
WO2013009102A3 (ko) * 2011-07-13 2013-04-11 (주)차바이오앤디오스텍 콜라겐, 히알루론산 유도체 및 포유류의 탯줄 유래 줄기세포를 포함하는 연골세포치료제
US8835405B2 (en) 2011-09-16 2014-09-16 China Medical University Inhibiting arthritis via injection of synergistic combination of hyaluronic acid and vitamin C and/or vitamin E
US11337994B2 (en) 2016-09-15 2022-05-24 University Of Utah Research Foundation In situ gelling compositions for the treatment or prevention of inflammation and tissue damage

Also Published As

Publication number Publication date
WO2007137674A1 (en) 2007-12-06
CA2653660A1 (en) 2007-12-06
ES2534763T3 (es) 2015-04-28
SI2021078T1 (sl) 2015-05-29
MX2008015212A (es) 2008-12-09
US9295690B2 (en) 2016-03-29
EP2786782A1 (en) 2014-10-08
CN101454048A (zh) 2009-06-10
KR20090014359A (ko) 2009-02-10
US20140221294A1 (en) 2014-08-07
US8765714B2 (en) 2014-07-01
ES2619309T3 (es) 2017-06-26
JP2009538840A (ja) 2009-11-12
HK1197040A1 (en) 2015-01-02
PL2786782T3 (pl) 2017-08-31
US20120165254A1 (en) 2012-06-28
SI2786782T1 (sl) 2017-06-30
HK1123235A1 (en) 2009-06-12
EP2786782B1 (en) 2017-03-08
AU2007268195A1 (en) 2007-12-06
ITPD20060219A1 (it) 2007-12-01
CA2653660C (en) 2014-07-29
PL2021078T3 (pl) 2015-08-31
DK2021078T3 (en) 2015-04-27
EP2021078A1 (en) 2009-02-11
CN101454048B (zh) 2013-06-19
JP5537933B2 (ja) 2014-07-02
EP2021078B1 (en) 2015-02-25

Similar Documents

Publication Publication Date Title
US9295690B2 (en) Sulphated hyaluronic acid for treating degenerative osteoarthritis
ES2374157T3 (es) Tratamiento para la sinovitis traumática y el cartílago articular dañado.
EP1423081A2 (en) Composition comprising glycosaminogycans and hyaluronidase inhibitors for the treatment of arthritic joints
Kamarul et al. A preliminary study of the effects of glucosamine sulphate and chondroitin sulphate on surgically treated and untreated focal cartilage damage
Agiba Nutraceutical formulations containing glucosamine and chondroitin sulphate in the treatment of osteoarthritis: Emphasis on clinical efficacy and formulation challenges
Sayed Aly Intra-articular drug delivery: a fast growing approach
TWI516269B (zh) 使用於炎症性腸疾病（ｉｂｄ）治療和預防之透明質酸混合物
JP2011037849A (ja) 消化性潰瘍及び十二指腸潰瘍の治療及び予防に使用されるヒアルロン酸混合物
WO2010121700A1 (en) Compositions containing hyaluronic acid, sulphated hyaluronic acid, calcium and vitamin d3 for the treatment of osteoarticular and musculoskeletal disorders
US9993496B1 (en) Method of administering hyaluronan formulation for supporting joint health
US20070142326A1 (en) Treatment of a condition in a mammal with administration of aminosugar and uses thereof
US10583153B1 (en) Method of administering hyaluronan formulation for maintaining and supporting joint health
WO2005034961A1 (en) Treatment of a condition in a mammal with adminisration of aminosugar and uses thereof
EP4360619A1 (en) Dosage form for intra-articular injection comprising colchicine and an anesthesic agent in the treatment of crystal-and non-crystal associated acute inflammatory arthritis
WO2023080853A1 (en) Rheologically synovial fluid-like hydrogel formulations for using in intra-articular applications
EP2318014B1 (en) New composition for treating autoimmune disorders
Volk Connective tissue Part 4: Glycosaminoglycans
AU2002312564A1 (en) Composition comprising glycosaminogycans and hyaluronidase inhibitors for the treatment of arthritic joints
CA2779838A1 (en) Treatment of cytokine mediated conditions

Legal Events

Date Code Title Description
AS Assignment

Owner name: FIDIA FARMACEUTICI S.P.A., ITALY

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:CALLEGARO, LANFRANCO;RENIER, DAVIDE;REEL/FRAME:021894/0361

Effective date: 20081021

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION