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WO2006067608A1 - Formulations aqueuses a base de hyaluronate de sodium a usage parenteral - Google Patents

Formulations aqueuses a base de hyaluronate de sodium a usage parenteral Download PDF

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Publication number
WO2006067608A1
WO2006067608A1 PCT/IB2005/003918 IB2005003918W WO2006067608A1 WO 2006067608 A1 WO2006067608 A1 WO 2006067608A1 IB 2005003918 W IB2005003918 W IB 2005003918W WO 2006067608 A1 WO2006067608 A1 WO 2006067608A1
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WO
WIPO (PCT)
Prior art keywords
naoh
aqueous formulation
naci
acid
sodium hyaluronate
Prior art date
Application number
PCT/IB2005/003918
Other languages
English (en)
Inventor
Stefano Carlino
Original Assignee
Laboratoire Medidom S.A.
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 Laboratoire Medidom S.A. filed Critical Laboratoire Medidom S.A.
Publication of WO2006067608A1 publication Critical patent/WO2006067608A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • 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
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • 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

Definitions

  • the present invention concerns aqueous formulations based on sodium hyaluronate for parenteral use.
  • Sodium hyaluronate is the sodium salt of hyaluronic acid, a mucoid polysaccharide of biological origin, which is known as one of the major components of synovial fluid and which is also present in various connective tissues such as skin and cartilage.
  • hyaluronic acid is a member of glycosaminoglycans and it is constituted by alternating and repeating units of D-glucuronic acid and N-acetyl- D-glucosamine, to form a linear chain having a molecular weight up to 13 x 10 6 Daltons.
  • aqueous formulations based on sodium hyaluronate for intra-articular use are usually composed of sodium hyaluronate as active ingredient, and further of some salts as sodium chloride for obtaining the physiological osmolarity of 270 - 330 mOsm/l and sodium phosphate as a buffer for maintaining the pH in the range of 6.8 to 7.6, preferably at a physiological pH of 7.4.
  • WO-A-89 01777 discloses a lubricant composition for intra-articular use, which is useful to reduce the coefficient of kinetic friction imparted to the boundary surface of a joint upon articulation, said lubricant composition comprising at least one phospholipid in a relatively high concentration and hyaluronic acid or a water soluble salt thereof in phosphate-buffered saline solution.
  • HA with a high molecular weight in particular with an average molecular weight above 500'0OO Daltons, is preferred in many applications in view of the superior visco-elastic properties, residence time and tolerance in the body compared to lower molecular weight HA.
  • Known aqueous HA formulations however suffer from degradation by hyaluronidase enzymes, and as a consequence a deterioration of the sought after properties of the HA.
  • An object of this invention is to provide an aqueous high molecular weight HA formulation for parenteral uses, such as for intra-articular use or for tissue augmentation, that is stable over a long period of time, in particular that is resistant to degradation by enzymes.
  • hyaluronate polymer by hyaluronidase In order to overcome the problem of degradability of hyaluronate polymer by hyaluronidase, the inventors of the present invention have made extensive studies to provide an aqueous formulation based on sodium hyaluronate for parenteral use, such as for intra-articular use or for soft tissue augmentation, which has an improved resistance to degradation of hyaluronate polymer by hyaluronidase and consequently which has, inter alia, an increased residence time at the site of application.
  • the inventors have found that the presence of sodium chloride in known aqueous HA formulations, which is primarily intended to provide a physiological osmolarity for parenteral use, surprisingly has an adverse influence on the resistance to hyaluronidase degradation of the HA polymer.
  • the inventors have further found that in the absence of sodium chloride, a wide range of amphoters - which includes fatty acids, fatty acid esters, phospholipids, sphingolipids, and gangliosides - inhibit hyaluronidase enzyme activity very effectively.
  • the object of the invention has been achieved as a result of the unexpected findings that sodium chloride, which is usually contained in known aqueous sodium hyaluronate formulations for parenteral use, may be advantageously replaced by a non saline physiologically acceptable osmogen, to provide an aqueous formulation having physiological osmolarity.
  • a suitable buffer can be added, unless the osmogen itself can act as a buffer in the physiological range.
  • the hyaluronate polymer In combination with an amphoter, acting as a hyaluronidase activity inhibitor, the hyaluronate polymer has a resistance to hyaluronidase that is, in vitro, more than 30 times greater than hyaluronate polymer contained in the known formulations containing sodium chloride.
  • the non saline osmogen may advantageously be an amino acid selected from a group comprising histidine, valine, proline and cysteine.
  • the osmogen may also be: a polyalchohol phosphoric ester such as glycerophosphate; a polyol such as mannitol, sorbitol, glycerol or xylitol; a monosaccharide such as glucose, galactose, xylose, fructose, galactosamine, glucosamine, neuraminic acid, and glucuronic acid; or a disaccharide such as sucrose, maltose and lactose.
  • a polyalchohol phosphoric ester such as glycerophosphate
  • a polyol such as mannitol, sorbitol, glycerol or xylitol
  • a monosaccharide such as glucose, galactose, x
  • an advantage of the use of an amino acid selected from a group comprising histidine, valine, proline and cysteine, and particularly histidine is that the amino acid itself acts as a buffer in the physiological pH and gives the physiological osmolarity when added in an appropriate amount, thus providing an aqueous formulation for parenteral use comprising sodium hyaluronate having an improved resistance to degradation by hyaluronidase due to the absence of sodium chloride and phosphate buffer and therefore an increased residence time at the site of application.
  • an aqueous formulation for parenteral use such as intra-articular use or soft tissue augmentation, comprising sodium hyaluronate having a very high resistance to degradation by hyaluronidase, and therefore an optimal residence time at the site of application, may be obtained by adding a small amount of an amphoter (amphoteric compound) such as a phospholipid to a non-saline aqueous formulation comprising sodium hyaluronate,or other salt of hyaluronic acid, and a non saline osmogen such as histidine.
  • amphoter amphoteric compound
  • Fig. 1 represents a graph showing elastic module kinetics during incubation at 37°C with hyaluronidase in two different formulations, namely a formulation according to the present invention and a comparative formulation.
  • the aqueous formulation for parenteral use of the present invention comprises between 0.01 to 3 % w/v sodium hyaluronate having a molecular weight from 500,000 to 5,000,000 Daltons.
  • the molecular weight of sodium hyaluronate used in the present invention may be determined by known techniques such as gel permeation chromatography or by measuring intrinsic viscosity.
  • Said aqueous formulation for parenteral use of the present invention is characterized in that it further comprises non saline osmogen in an effective amount to impart to the aqueous formulation a physiological osmolarity of from 270 - 330 mOsm/l and a physiological pH from 6.8 - 7.6, preferably 7.4., or a non saline osmogen plus a suitable buffer capable of maintaining the pH in the physiological range.
  • Sodium hyaluronate of molecular weights lower than 500,000 D are not appropriate for use in the present invention because of the insufficient visco- elastic properties, the lower residence time and reduced tolerance and increased irritation in the body compared to higher molecular weight HA.
  • a formulation having a content of sodium hyaluronate greater than 3 % wt/v is not appropriate for parenteral use since it forms a very high viscosity gel that is difficult to administer by injection, for example.
  • the sodium hyaluronate is used in an amount of 0.2 to 2 % wt/v, based on the total aqueous formulation.
  • Said aqueous formulation for intra-articular use of the present invention comprises both a non saline osmogen in an effective concentration to impart to the aqueous formulation a physiological osmolarity of from 270-330 mOsm/l and a physiological pH of from 6.8-7.6, or a non saline osmogen plus a suitable buffer.
  • the non saline osmogen is preferably an amino acid selected from a group comprising histidine, valine, proline and cysteine, such substances being able to buffer at the physiological pH.
  • a suitable buffer such as an amino acid selected from a group comprising histidine, valine, proline, asparagine and cysteine
  • an osmogen such as a polyalchohol phosphoric ester such as glycerophosphate; a polyol such as mannitol, sorbitol, glycerol or xylitol; a monosaccharide such as glucose, galactose, xylose, fructose, galactosamine, glucosamine, neuraminic acid, and glucuronic acid; or a disaccharide such as sucrose, maltose and lactose.
  • an osmogen such as a polyalchohol phosphoric ester such as glycerophosphate
  • a polyol such as mannitol, sorbitol, glycerol or xylitol
  • a monosaccharide such as glucose, galactose,
  • sodium hyaluronate also contributes to the osmolarity of the formulation, said contribution depending on the concentration and molecular weight of sodium hyaluronate present in the formulation.
  • the effective concentration range of osmogen to impart to the aqueous formulation a physiological osmolarity of from 270-330 mOsm/l will depend on the concentration and molecular weight of the sodium hyaluronate present in the formulation.
  • a solution of 36, 40 and 44 g/l of histidine gives an osmolarity of 220, 246 and 268 mOsm/l, respectively.
  • sodium hyaluronate having a molecular weight of 1'80OOOO D is added in an amount of 1 % w/v to the solution, the osmolarity becomes 271 , 298 and 310 m ⁇ sm/l, respectively.
  • sodium hyaluronate having an average molecular weight of 1'800'000 D in an amount of 1 % w/v contributes to about 50 m ⁇ sm/l.
  • An advantage of using an amino acid, and in particular histidine, as an osmogen, is that it results in a physiological pH at all concentrations of histidine if the physiological osmolarity is achieved in the formulation containing sodium hyaluronate. An additional buffer is thus not needed.
  • Presence of histidine in an effective amount to impart a physiological osmolarity in the aqueous formulation containing sodium hyaluronate allows to improve the resistance of hyaluronate to hyaluronidase by 2 - 3 times compared with classical formulations containing sodium chloride and phosphate buffer instead of histidine.
  • the aqueous formulation of the present invention may be prepared according to conventional techniques by adding histidine in water previously heated at a temperature up to 40 0 C and stirring until complete dissolution of histidine into water, and then by further adding thereto sodium hyaluronate and stirring until complete dissolution of sodium hyaluronate into the histidine solution.
  • the aqueous formulation further contains up to 1 % w/v phospholipid based on the total aqueous formulation.
  • Phospholipids which can be used in the present invention may be any naturally or artificially synthesized phospholipids and are preferably selected from phosphatide acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, sphingomyelin and derivatives thereof.
  • Presence of a small amount of phospholipid in the aqueous formulation of the present invention containing sodium hyaluronate and histidine is advantageous in the sense that it allows to impart to hyaluronate a drastically improved resistance to degradation by hyaluronidase.
  • the aqueous formulation of the present invention further containing phospholipid may be prepared according to conventional techniques by adding a suspension of phospholipid, previously prepared by adding phospholipid to water heated at a temperature up to 50 0 C, to the aqueous formulation according to the present invention containing histidine and sodium hyaluronate and stirring until the formulation be homogeneous.
  • buffers including: common buffers such as citric acid, cacodylic acid Sodium salt-HCI, and imidazole-HCI; peptides such as carnosine, amino acid such as histidine, proline, valine or cysteine; and Zwitterionic buffers such as Glycyl-glycine-piperazine ⁇ HCI-NaOH, MES-NaOH-NaCI, TRIS-malic acid-NaOH, ADA-NaOH-NaCI, ACES-NaOH-NaCI, BES-NaOH-NaCI, MOPS- NaOH-NaCI, TES-NaOH-NaCI, MOPS-KOH, HEPES-NaOH-NaCI, TRIS-HCI, HEPPSO-NaOH, and BICINE-NaOH-NaCI.
  • common buffers such as citric acid, cacodylic acid Sodium salt-HCI, and imidazole-HCI
  • peptides such as car
  • the aqueous formulation for parenteral use of the present invention is particularly useful for intra-articular administration or soft tissue augmentation and has the advantage of showing an increased residence time at the site of application for the reason that hyaluronate polymer contained in the formulation has an improved resistance to degradation by hyaluronidase.
  • Example 1 Preparation of a formulation according to a preferred embodiment of the present invention containing 1 % w/v of sodium hvaluronate, in which the formulation contains a single substance that acts as an osmogen and as a buffer.
  • the formulation is prepared as follows:
  • Solution B is poured into Solution A under stirring conditions, to prepare 2 liter of a formulation according to an embodiment of the present invention.
  • Example 2 Preparation of a formulation according to a preferred embodiment of the present invention containing 2 % w/v of sodium hvaluronate. in which the the formulation contains a substance that acts as an osmogen and another substance which acts as a buffer.
  • the formulation is prepared as follows:
  • Solution A and solution B are mixed together and the pH is adjusted at 7.4 with sulfuric acid 10% in water for injection.
  • FIG. 1 the elastic module kinetics of the formulation according to the above example (IF), and a conventional HA saline aqueous formulation (CF) is measured during incubation with hyaluronidase at 37 degrees Celsius.
  • the known formulation is a formulation at 2% concentration of sodium hyaluronate in a saline aqueous solution commercialised by the firm TRB Chemedica SA (Switzerland) under the tradename "VISIOL".

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • General Chemical & Material Sciences (AREA)
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  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Medicinal Preparation (AREA)
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Abstract

L'invention porte sur une formulation aqueuse à usage parentéral qui comprend un hyaluronate de sodium ayant un poids moléculaire compris entre 500 000 et 5 000 000 D dans une quantité comprise entre 0,01 et 3 % w/v, sur la base de la formulation aqueuse, un osmogène non salin acceptable d'un point de vue physiologique dans une quantité effective de façon à conférer à la formulation aqueuse une osmolarité physiologique comprise entre 270 et 330 mOsm/l, et un amphotère agissant comme inhibiteur de l'activité de la hyaluronidase.
PCT/IB2005/003918 2004-12-22 2005-12-14 Formulations aqueuses a base de hyaluronate de sodium a usage parenteral WO2006067608A1 (fr)

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EP04405792 2004-12-22
EP04405792.5 2004-12-22

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* Cited by examiner, † Cited by third party
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FR2918276A1 (fr) * 2007-07-02 2009-01-09 Anteis Sa "utilisation d'un gel de polysaccharide(s)naturel(s)pour la preparation d'une formulation injectable de traitement des degenerescences articulaires"
FR2938187A1 (fr) * 2008-11-07 2010-05-14 Anteis Sa Composition injectable a base d'acide hyaluronique ou l'un de ses sels, de polyols et de lidocaine, sterilisee a la chaleur
ITMI20092256A1 (it) * 2009-12-21 2011-06-22 Solartium Entpr Ltd Uso di una combinazione per il trattamento dell'osteoartrosi
WO2011110894A2 (fr) 2010-03-12 2011-09-15 Allergan Industrie Sas Composition fluide pour l'amélioration d'états cutanés
ITBS20100197A1 (it) * 2010-12-06 2012-06-07 Paoli Ambrosi Gianfranco De Nuovo composto di carnosina
RU2454219C2 (ru) * 2007-07-02 2012-06-27 Антэ С.А. Применение геля из природного полисахарида (природных полисахаридов) для приготовления годной для инъекции композиции при лечении дегенераций суставов
WO2012143876A1 (fr) * 2011-04-19 2012-10-26 Anteis S.A. Formulation aqueuse stérile et injectable pour l'administration dans l'espace intra-articulaire d'une articulation intra-articulaire
WO2013076162A1 (fr) * 2011-11-21 2013-05-30 Université Libre de Bruxelles Formulations utiles dans le traitement de maladies ostéoarticulaires
WO2013076160A1 (fr) * 2011-11-21 2013-05-30 Université Libre de Bruxelles Formulations à libération prolongée utiles dans le traitement de maladies
US8691279B2 (en) 2010-03-22 2014-04-08 Allergan, Inc. Polysaccharide and protein-polysaccharide cross-linked hydrogels for soft tissue augmentation
US8853184B2 (en) 2007-11-30 2014-10-07 Allergan, Inc. Polysaccharide gel formulation having increased longevity
US8883139B2 (en) 2010-08-19 2014-11-11 Allergan Inc. Compositions and soft tissue replacement methods
US8889123B2 (en) 2010-08-19 2014-11-18 Allergan, Inc. Compositions and soft tissue replacement methods
WO2015006460A1 (fr) 2013-07-10 2015-01-15 Matrix Biology Institute Compositions d'acide hyaluronique à haute élasticité et leurs utilisations
US8946192B2 (en) 2010-01-13 2015-02-03 Allergan, Inc. Heat stable hyaluronic acid compositions for dermatological use
US9005605B2 (en) 2010-08-19 2015-04-14 Allergan, Inc. Compositions and soft tissue replacement methods
US9062130B2 (en) 2003-04-10 2015-06-23 Allergan Industrie Sas Cross-linking of low-molecular weight and high-molecular weight polysaccharides, preparation of injectable monophase hydrogels, polysaccharides and hydrogels obtained
US9089519B2 (en) 2008-08-04 2015-07-28 Allergan Industrie Sas Hyaluronic acid-based gels including lidocaine
US9114188B2 (en) 2010-01-13 2015-08-25 Allergan, Industrie, S.A.S. Stable hydrogel compositions including additives
US9149422B2 (en) 2011-06-03 2015-10-06 Allergan, Inc. Dermal filler compositions including antioxidants
US9228027B2 (en) 2008-09-02 2016-01-05 Allergan Holdings France S.A.S. Threads of Hyaluronic acid and/or derivatives thereof, methods of making thereof and uses thereof
US9265761B2 (en) 2007-11-16 2016-02-23 Allergan, Inc. Compositions and methods for treating purpura
US9393263B2 (en) 2011-06-03 2016-07-19 Allergan, Inc. Dermal filler compositions including antioxidants
US9408797B2 (en) 2011-06-03 2016-08-09 Allergan, Inc. Dermal filler compositions for fine line treatment
US9795711B2 (en) 2011-09-06 2017-10-24 Allergan, Inc. Hyaluronic acid-collagen matrices for dermal filling and volumizing applications
US10004824B2 (en) 2015-05-11 2018-06-26 Laboratoires Vivacy Compositions comprising at least one polyol and at least one anesthetic
US10028976B2 (en) * 2007-07-02 2018-07-24 Aptissen Sa Injectable formulation of natural polysaccharide and polyol for treatment of osteoarthritis
US10722444B2 (en) 2014-09-30 2020-07-28 Allergan Industrie, Sas Stable hydrogel compositions including additives
US11083684B2 (en) 2011-06-03 2021-08-10 Allergan Industrie, Sas Dermal filler compositions
US11260015B2 (en) 2015-02-09 2022-03-01 Allergan Industrie, Sas Compositions and methods for improving skin appearance
CN114317497A (zh) * 2021-12-14 2022-04-12 华熙生物科技股份有限公司 一种检测用透明质酸酶液体制剂及其应用
US11844878B2 (en) 2011-09-06 2023-12-19 Allergan, Inc. Crosslinked hyaluronic acid-collagen gels for improving tissue graft viability and soft tissue augmentation

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0138572A2 (fr) * 1983-10-11 1985-04-24 FIDIA S.p.A. Fractions d'acide hyaluronique ayant une activité pharmaceutique, méthodes pour leur préparation et compositions pharmaceutiques les contenant
WO1989001777A1 (fr) * 1987-08-25 1989-03-09 Macnaught Pty. Limited Composition lubrifiante pour le traitement d'affections rhumatismales
AU2320888A (en) * 1987-08-25 1989-03-31 Macnaught Pty Limited Hyaluronic acid lubricating compounds
US4957744A (en) * 1986-10-13 1990-09-18 Fidia, S.P.A. Cross-linked esters of hyaluronic acid
EP0499164A1 (fr) * 1991-02-12 1992-08-19 C.R. Bard, Inc. Compositions injectables pour remplacer les fluides lubrifiants corporels
US5234914A (en) * 1991-06-11 1993-08-10 Patent Biopharmaceutics, Inc. Methods of treating hemorrhoids and anorecial disease
US5679655A (en) * 1993-08-04 1997-10-21 Patent Biopharmaceutics, Inc. Method of treating lesions resulting from genital herpes with hyaluronic acid-urea pharmaceutical compositions
US20010041671A1 (en) * 2000-04-07 2001-11-15 Napoli Guido Di Ophthalmic formulations

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0138572A2 (fr) * 1983-10-11 1985-04-24 FIDIA S.p.A. Fractions d'acide hyaluronique ayant une activité pharmaceutique, méthodes pour leur préparation et compositions pharmaceutiques les contenant
US4957744A (en) * 1986-10-13 1990-09-18 Fidia, S.P.A. Cross-linked esters of hyaluronic acid
WO1989001777A1 (fr) * 1987-08-25 1989-03-09 Macnaught Pty. Limited Composition lubrifiante pour le traitement d'affections rhumatismales
AU2320888A (en) * 1987-08-25 1989-03-31 Macnaught Pty Limited Hyaluronic acid lubricating compounds
EP0499164A1 (fr) * 1991-02-12 1992-08-19 C.R. Bard, Inc. Compositions injectables pour remplacer les fluides lubrifiants corporels
US5234914A (en) * 1991-06-11 1993-08-10 Patent Biopharmaceutics, Inc. Methods of treating hemorrhoids and anorecial disease
US5679655A (en) * 1993-08-04 1997-10-21 Patent Biopharmaceutics, Inc. Method of treating lesions resulting from genital herpes with hyaluronic acid-urea pharmaceutical compositions
US20010041671A1 (en) * 2000-04-07 2001-11-15 Napoli Guido Di Ophthalmic formulations

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US11045490B2 (en) 2003-04-10 2021-06-29 Allergan Industrie, Sas Injectable monophase hydrogels
US9062130B2 (en) 2003-04-10 2015-06-23 Allergan Industrie Sas Cross-linking of low-molecular weight and high-molecular weight polysaccharides, preparation of injectable monophase hydrogels, polysaccharides and hydrogels obtained
US10080767B2 (en) 2003-04-10 2018-09-25 Allergan Industrie Sas Injectable monophase hydrogels
US10653716B2 (en) 2003-04-10 2020-05-19 Allergan Industrie, Sas Injectable monophase hydrogels
EP3498262A1 (fr) * 2007-07-02 2019-06-19 Aptissen SA Gel injectable d'acide hyaluronique
JP2010531863A (ja) * 2007-07-02 2010-09-30 アンタイス エス．エイ． 関節変性の治療のための注射用製剤の製造のための天然ポリサッカライドゲルの使用
EP3498262B1 (fr) 2007-07-02 2021-09-01 Aptissen SA Gel injectable d'acide hyaluronique
FR2918276A1 (fr) * 2007-07-02 2009-01-09 Anteis Sa "utilisation d'un gel de polysaccharide(s)naturel(s)pour la preparation d'une formulation injectable de traitement des degenerescences articulaires"
EP2173324B1 (fr) 2007-07-02 2019-04-10 Aptissen SA Gel injectable d'acide hyaluronique pour le traitement des degenerescences articulaires
RU2454219C2 (ru) * 2007-07-02 2012-06-27 Антэ С.А. Применение геля из природного полисахарида (природных полисахаридов) для приготовления годной для инъекции композиции при лечении дегенераций суставов
EP2173324A2 (fr) 2007-07-02 2010-04-14 Anteis SA Gel injectable d'acide hyaluronique pour le traitement des degenerescences articulaires
US10028976B2 (en) * 2007-07-02 2018-07-24 Aptissen Sa Injectable formulation of natural polysaccharide and polyol for treatment of osteoarthritis
US9138405B2 (en) 2007-07-02 2015-09-22 Aptissen Sa Use of a natural polysaccharide gel for the preparation of an injectable formulation for treatment of articular degeneration
CN104825482A (zh) * 2007-07-02 2015-08-12 爱体神有限公司 天然多糖凝胶剂在制备用于治疗关节退行性变的可注射制剂中的应用
WO2009024670A3 (fr) * 2007-07-02 2009-04-23 Anteis Sa Gel injectable d ' acide hyaluronique pour le traitement des degenerescences articulaires
US9265761B2 (en) 2007-11-16 2016-02-23 Allergan, Inc. Compositions and methods for treating purpura
US8853184B2 (en) 2007-11-30 2014-10-07 Allergan, Inc. Polysaccharide gel formulation having increased longevity
US10391202B2 (en) 2008-08-04 2019-08-27 Allergan Industrie Sas Hyaluronic acid-based gels including lidocaine
US9089519B2 (en) 2008-08-04 2015-07-28 Allergan Industrie Sas Hyaluronic acid-based gels including lidocaine
US9238013B2 (en) 2008-08-04 2016-01-19 Allergan Industrie, Sas Hyaluronic acid-based gels including lidocaine
US11173232B2 (en) 2008-08-04 2021-11-16 Allergan Industrie, Sas Hyaluronic acid-based gels including lidocaine
US10328180B2 (en) 2008-08-04 2019-06-25 Allergan Industrie, S.A.S. Hyaluronic acid-based gels including lidocaine
US9089517B2 (en) 2008-08-04 2015-07-28 Allergan Industrie Sas Hyaluronic acid-based gels including lidocaine
US9089518B2 (en) 2008-08-04 2015-07-28 Allergan Industrie Sas Hyaluronic acid-based gels including lidocaine
US9358322B2 (en) 2008-08-04 2016-06-07 Allergan Industrie Sas Hyaluronic acid-based gels including lidocaine
US11020512B2 (en) 2008-08-04 2021-06-01 Allergan Industrie, Sas Hyaluronic acid-based gels including lidocaine
US10485896B2 (en) 2008-08-04 2019-11-26 Allergan Industrie Sas Hyaluronic acid-based gels including lidocaine
US9228027B2 (en) 2008-09-02 2016-01-05 Allergan Holdings France S.A.S. Threads of Hyaluronic acid and/or derivatives thereof, methods of making thereof and uses thereof
US9861570B2 (en) 2008-09-02 2018-01-09 Allergan Holdings France S.A.S. Threads of hyaluronic acid and/or derivatives thereof, methods of making thereof and uses thereof
US11154484B2 (en) 2008-09-02 2021-10-26 Allergan Holdings France S.A.S. Threads of hyaluronic acid and/or derivatives thereof, methods of making thereof and uses thereof
FR2938187A1 (fr) * 2008-11-07 2010-05-14 Anteis Sa Composition injectable a base d'acide hyaluronique ou l'un de ses sels, de polyols et de lidocaine, sterilisee a la chaleur
EP2349203B2 (fr) † 2008-11-07 2020-02-26 Anteis S.A. Composition injectable a base d'acide hyaluronique ou l'un de ses sels, de polyols et de lidocaïne, sterilisée à la chaleur
EP2676658B1 (fr) 2008-11-07 2015-09-16 Anteis SA Composition injectable à base d'acide hyaluronique, de polyol(s) et de lidocaïne, stérilisée à la chaleur
ITMI20092256A1 (it) * 2009-12-21 2011-06-22 Solartium Entpr Ltd Uso di una combinazione per il trattamento dell'osteoartrosi
WO2011076596A1 (fr) * 2009-12-21 2011-06-30 Professional Dietetics S.R.L. Combinaison pour le traitement de l'ostéoarthrite
US20130310437A1 (en) * 2009-12-21 2013-11-21 Professional Dietetics S.R.L. Combination for the treatment of osteoarthritis
CN102665708B (zh) * 2009-12-21 2014-11-05 专业营养有限公司 用于治疗骨关节炎的组合
US9040575B2 (en) 2009-12-21 2015-05-26 Professional Dietetics, S.R.L. Combination for the treatment of osteoarthritis
CN102665708A (zh) * 2009-12-21 2012-09-12 专业营养有限公司 用于治疗骨关节炎的组合
US10806821B2 (en) 2010-01-13 2020-10-20 Allergan Industrie, Sas Heat stable hyaluronic acid compositions for dermatological use
US10220113B2 (en) 2010-01-13 2019-03-05 Allergan Industrie, Sas Heat stable hyaluronic acid compositions for dermatological use
US8946192B2 (en) 2010-01-13 2015-02-03 Allergan, Inc. Heat stable hyaluronic acid compositions for dermatological use
US9855367B2 (en) 2010-01-13 2018-01-02 Allergan Industrie, Sas Heat stable hyaluronic acid compositions for dermatological use
US9114188B2 (en) 2010-01-13 2015-08-25 Allergan, Industrie, S.A.S. Stable hydrogel compositions including additives
US10449268B2 (en) 2010-01-13 2019-10-22 Allergan Industrie, S.A.S. Stable hydrogel compositions including additives
US9655991B2 (en) 2010-01-13 2017-05-23 Allergan Industrie, S.A.S. Stable hydrogel compositions including additives
US9333160B2 (en) 2010-01-13 2016-05-10 Allergan Industrie, Sas Heat stable hyaluronic acid compositions for dermatological use
AU2010348090B2 (en) * 2010-03-12 2015-09-03 Allergan Industrie Sas A fluid composition comprising a hyaluronan polymer and mannitol for improving skin condition
JP2015164948A (ja) * 2010-03-12 2015-09-17 アラーガン・アンデュストリー・ソシエテ・パール・アクシオン・サンプリフィエＡｌｌｅｒｇａｎ Ｉｎｄｕｓｔｒｉｅ Ｓａｓ 皮膚状態を改善するための流体組成物
CN102905677A (zh) * 2010-03-12 2013-01-30 阿勒根工业有限公司 用于改善皮肤状况的包含透明质烷聚合物和甘露糖醇的流体组合物
WO2011110894A2 (fr) 2010-03-12 2011-09-15 Allergan Industrie Sas Composition fluide pour l'amélioration d'états cutanés
US8921338B2 (en) 2010-03-12 2014-12-30 Allergan Industrie, Sas Fluid compositions for improving skin conditions
WO2011110894A3 (fr) * 2010-03-12 2011-11-24 Allergan Industrie Sas Composition fluide pour l'amélioration d'états cutanés
US9585821B2 (en) 2010-03-12 2017-03-07 Allergan Industrie Sas Methods for making compositions for improving skin conditions
US9125840B2 (en) 2010-03-12 2015-09-08 Allergan Industrie Sas Methods for improving skin conditions
KR101764451B1 (ko) * 2010-03-12 2017-08-02 알러간 인더스트리 에스에이에스 피부 상태 개선을 위한 히알루론안 폴리머 및 만니톨을 포함하는 유체 조성물
JP2013522283A (ja) * 2010-03-12 2013-06-13 アラーガン・アンデュストリー・ソシエテ・パール・アクシオン・サンプリフィエ 皮膚状態を改善するための流体組成物
US10905797B2 (en) 2010-03-22 2021-02-02 Allergan, Inc. Polysaccharide and protein-polysaccharide cross-linked hydrogels for soft tissue augmentation
US9012517B2 (en) 2010-03-22 2015-04-21 Allergan, Inc. Polysaccharide and protein-polysaccharide cross-linked hydrogels for soft tissue augmentation
US9480775B2 (en) 2010-03-22 2016-11-01 Allergan, Inc. Polysaccharide and protein-polysaccharide cross-linked hydrogels for soft tissue augmentation
US8691279B2 (en) 2010-03-22 2014-04-08 Allergan, Inc. Polysaccharide and protein-polysaccharide cross-linked hydrogels for soft tissue augmentation
US8889123B2 (en) 2010-08-19 2014-11-18 Allergan, Inc. Compositions and soft tissue replacement methods
US9005605B2 (en) 2010-08-19 2015-04-14 Allergan, Inc. Compositions and soft tissue replacement methods
US8883139B2 (en) 2010-08-19 2014-11-11 Allergan Inc. Compositions and soft tissue replacement methods
WO2012076961A3 (fr) * 2010-12-06 2012-11-01 Gianfranco De Paoli Ambrosi Nouveau composé de carnosine
ITBS20100197A1 (it) * 2010-12-06 2012-06-07 Paoli Ambrosi Gianfranco De Nuovo composto di carnosina
RU2602297C2 (ru) * 2010-12-06 2016-11-20 ПАОЛИ АМБРОЗИ Джанфранко ДЕ Смеси карнозина и гиалуроновой кислоты и их применение
CN103282032A (zh) * 2010-12-06 2013-09-04 詹弗兰科·德保利安布罗西 肌肽-透明质酸混合物及它们的用途
US9475887B2 (en) 2010-12-06 2016-10-25 Gianfranco De Paoli Ambrosi Carnosine hyaluronic acid mixtures and their use
WO2012143876A1 (fr) * 2011-04-19 2012-10-26 Anteis S.A. Formulation aqueuse stérile et injectable pour l'administration dans l'espace intra-articulaire d'une articulation intra-articulaire
US9149422B2 (en) 2011-06-03 2015-10-06 Allergan, Inc. Dermal filler compositions including antioxidants
US9408797B2 (en) 2011-06-03 2016-08-09 Allergan, Inc. Dermal filler compositions for fine line treatment
US9737633B2 (en) 2011-06-03 2017-08-22 Allergan, Inc. Dermal filler compositions including antioxidants
US11083684B2 (en) 2011-06-03 2021-08-10 Allergan Industrie, Sas Dermal filler compositions
US10624988B2 (en) 2011-06-03 2020-04-21 Allergan Industrie, Sas Dermal filler compositions including antioxidants
US9393263B2 (en) 2011-06-03 2016-07-19 Allergan, Inc. Dermal filler compositions including antioxidants
US11000626B2 (en) 2011-06-03 2021-05-11 Allergan Industrie, Sas Dermal filler compositions including antioxidants
US10994049B2 (en) 2011-06-03 2021-05-04 Allergan Industrie, Sas Dermal filler compositions for fine line treatment
US9962464B2 (en) 2011-06-03 2018-05-08 Allergan, Inc. Dermal filler compositions including antioxidants
US9795711B2 (en) 2011-09-06 2017-10-24 Allergan, Inc. Hyaluronic acid-collagen matrices for dermal filling and volumizing applications
US11844878B2 (en) 2011-09-06 2023-12-19 Allergan, Inc. Crosslinked hyaluronic acid-collagen gels for improving tissue graft viability and soft tissue augmentation
US11833269B2 (en) 2011-09-06 2023-12-05 Allergan, Inc. Hyaluronic acid-collagen matrices for dermal filling and volumizing applications
US9821086B2 (en) 2011-09-06 2017-11-21 Allergan, Inc. Hyaluronic acid-collagen matrices for dermal filling and volumizing applications
US10434214B2 (en) 2011-09-06 2019-10-08 Allergan, Inc. Hyaluronic acid-collagen matrices for dermal filling and volumizing applications
WO2013076160A1 (fr) * 2011-11-21 2013-05-30 Université Libre de Bruxelles Formulations à libération prolongée utiles dans le traitement de maladies
WO2013076162A1 (fr) * 2011-11-21 2013-05-30 Université Libre de Bruxelles Formulations utiles dans le traitement de maladies ostéoarticulaires
WO2015006460A1 (fr) 2013-07-10 2015-01-15 Matrix Biology Institute Compositions d'acide hyaluronique à haute élasticité et leurs utilisations
US10722444B2 (en) 2014-09-30 2020-07-28 Allergan Industrie, Sas Stable hydrogel compositions including additives
US11260015B2 (en) 2015-02-09 2022-03-01 Allergan Industrie, Sas Compositions and methods for improving skin appearance
US12011500B2 (en) 2015-02-09 2024-06-18 Allergan Industrie, Sas Compositions and methods for improving skin appearance
US10004824B2 (en) 2015-05-11 2018-06-26 Laboratoires Vivacy Compositions comprising at least one polyol and at least one anesthetic
CN114317497A (zh) * 2021-12-14 2022-04-12 华熙生物科技股份有限公司 一种检测用透明质酸酶液体制剂及其应用

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