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EP3324981A1 - Nouvelle utilisation d'acide hyaluronique - Google Patents

Nouvelle utilisation d'acide hyaluronique

Info

Publication number
EP3324981A1
EP3324981A1 EP16750610.4A EP16750610A EP3324981A1 EP 3324981 A1 EP3324981 A1 EP 3324981A1 EP 16750610 A EP16750610 A EP 16750610A EP 3324981 A1 EP3324981 A1 EP 3324981A1
Authority
EP
European Patent Office
Prior art keywords
hyaluronic acid
crosslinked
use according
periosteum
bone
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.)
Withdrawn
Application number
EP16750610.4A
Other languages
German (de)
English (en)
Inventor
Tracey Lennemann
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.)
Individual
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of EP3324981A1 publication Critical patent/EP3324981A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/728Hyaluronic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61CDENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C19/00Dental auxiliary appliances
    • A61C19/06Implements for therapeutic treatment
    • A61C19/063Medicament applicators for teeth or gums, e.g. treatment with fluorides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/28Bones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02Inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/28Bones
    • A61F2002/2817Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]

Definitions

  • the invention relates to a novel use of a hyaluronic acid in gels crosslinked or in a mixture of crosslinked and uncrosslinked form.
  • Hyaluronic acid or hyaluronan a glucosaminoglycan
  • ECM extracellular matrix
  • CNS central nervous system
  • HA is a polymer consisting of monomeric structural units of the disaccharide of D-glucuronic acid and N-acetyl-D-glucosamine which are polymerized in the body of vertebrates of HA synthases.
  • the chain length of the polymer typically comprises 250 to 50,000 disaccharide units, which corresponds to a molecular weight of about 95 kD to about 19,000 kD.
  • HA has an exceptionally high water binding capacity (up to 6 1 water per 1 g HA) and viscoelasticity, which forms the basis for its importance as a structural component.
  • HA Because of its complex interactions with matrix components and cells because of their physicochemical and biological properties, HA also plays a very diverse role in physiological events, which has not yet been fully elucidated.
  • Some important properties besides the structural properties of HA are a fibroblast activating property in the skin, a significant bacteriostatic effect of high and medium molecular weight HA, an angiogenic effect of low molecular weight HA, and surprisingly an anti-angiogenic effect of high molecular weight HA osteogenic effect.
  • non-animal biotechnological recombinant HA is currently used in uncrosslinked or partially crosslinked form, especially for injection into the joint space of arthritic joints, in dentistry for injection into the periodontal ligament, in hydrogels for wound care Nasal sprays and eye drops, used for wrinkle injection, modeling of lips and other body shaping.
  • Cosmetics mainly use degradation fragments of HA with a relatively low molecular weight (eg 50 to 130 kD).
  • the object of the invention was to improve the efficacy of hyaluronic acid in bone-near tissues and possibly in the bone itself by a suitable supply of hyaluronic acid.
  • the invention relates to the use of a hyaluronic acid-containing gel for healing and / or regenerating bone and bone surrounding tissue in humans or a vertebrate by injecting the hyaluronic acid in crosslinked form or in a mixture of crosslinked and uncrosslinked gels into the periosteum of a bone ,
  • FIG. 1 shows schematically the injection of hyaluronic acid into the periosteum of a
  • Figure 2 shows schematically the injection of hyaluronic acid into the periodontal ligament.
  • hyaluronic acid (HA) used in this invention may be either in crosslinked form or in a mixture of uncrosslinked and crosslinked form.
  • the uncrosslinked form of HA preferably used herein has a molecular weight in the range of about 730 kD to about 1,500 kD.
  • Crosslinked forms of FIA are commercially available in large numbers. They are generally injected in aqueous solution as a gel. Basically, a distinction is made between particulate cross-linked HA and large particles, for example in the range from a few ⁇ m to about 1000 ⁇ m, and homogeneous, nonparticular crosslinked monophasic HA, although this difference may not be as important in practice as often assumed. Numerous cross-linked HA products have been developed, especially for use as dermal fillers. Chain lengths and crosslinking agents can vary widely.
  • Chain length distribution (relatively short chains and long chains), the latter being able to form an interpenetrating network after crosslinking.
  • the chain length is generally 1,000 to 3,000 kD, but in some cases may be lower or higher.
  • Common crosslinking agents are e.g. Glutaraldehyde, 1-ethyl-3- (3-dimethylaminoproyl) carbodiimide (EDC), poly (ethylene glycol) diglycidyl ether (EX 801), divinylsulfone (DVS), 1, 4-butanediol diglycidyl ether (BDDE) and 1, 2, 7, 8 -Diepoxyoctan.
  • EDC 1-ethyl-3- (3-dimethylaminoproyl) carbodiimide
  • EX 801 poly (ethylene glycol) diglycidyl ether
  • DVD divinylsulfone
  • BDDE 4-butanediol diglycidyl ether
  • 1, 2, 7, 8 -Diepoxyoctan 1, 2, 7, 8 -Diepoxyoctan.
  • Crosslinked HA is used in an aqueous medium in gel form.
  • concentration of crosslinked HA in the aqueous medium will generally vary in commercially available products from about 18 to about 26 mg of crosslinked HA / ml aqueous medium, e.g. a phosphate buffer.
  • the ratio (w / v) of hyaluronic acid to aqueous medium, e.g. Phosphate buffer ranging from 1:35 to 1:45.
  • the gel used according to the invention may contain further drugs or adjuvants, such as preservatives or other auxiliaries customary in pharmacy.
  • Some common commercial cross-linked HA products for use as dermal fillers include Restylane ® (Fa. Galderma), Juvederm ® (Fa. Allergan), Belotero ® (Fa. Merz), Hyal ® (Fa. Merz).
  • Fa. Galderma Stylage ® (Fa. Laboraitres Vivacy) Puragen ® (Fa. Menotr Corporation), Emervel ® and Teosyal ® (Fa. Laboratoires Teoxane).
  • Periosyal ® (Laboratoires Teoxane) is used especially in dentistry.
  • the periosteum is a highly vascular connective tissue that surrounds all but the articular and muscular attachments. Its thickness is generally about 0.070 to 0.150 mm. It comprises at least two layers, an inner cambium layer and an outer fiber layer.
  • the inner layer contains numerous osteoblasts and osteogenic progenitor cells, the outer layer is composed of dense collagen fiber, fibroblasts and their progenitor cells.
  • a monophasic gel preparation with crosslinked HA or a gel preparation of crosslinked PIA with very small particles in the range up to the highest 20 ⁇ m is preferred, which may optionally also contain uncrosslinked HA.
  • a preferred product is, for example, with 5.0 to 10.0 wt .-% 1, 4-butanediol diglycidyl ether (BDDE) crosslinked HA shorter chain length with a concentration of 25 mg HA in phosphate buffer pH 7.3 ad 1 ml (commercially available as Periosyal ® Fill the company Laboratoires Teoxane) or with 1.9 to 4.0 wt .-% 1, 4-butanediol diglycidyl ether (BDDE) crosslinked HA long
  • Injection of the HA preparation into the periosteum is performed with a thin pointed needle preferably having an outside diameter of 0.30 - 0.50 mm (EN ISO 9626) or an electronic pen needle of similar diameter.
  • the needle is slowly introduced to the bone, until a resistance of Kompakta is no longer surmountable.
  • the preparation is slowly added e.g. in the course of 10 seconds to 2 minutes, preferably 20 seconds to 60 seconds, pushed through the needle into the periosteum. It is possible that only part of the injected HA preparation remains in the periosteum and excess drug swells into surrounding structures.
  • the same or another HA preparation may also be injected into soft tissue surrounding the periosteum of the bone. This too is described in more detail in the following example by means of an injection into the periodontal ligament of teeth.
  • the effect of the injection into the periosteum is to heal inflammation in the soft tissue surrounding the concha and in the cooking itself as well as to regenerate these structures, as further described below with reference to an example from the dental field. If necessary, the injection can be done every 1 to 2 weeks, e.g. be repeated once or twice.
  • Possible side effects of the injection may be e.g. Swelling, redness, pain, itching and sensitivity at the injection site.
  • Hyaluronic acid but there appear to be other factors, as treating the periodontal ligament alone without injection into the periosteum of the alveolar bone did not or only to a lesser extent observe these treatment successes.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Transplantation (AREA)
  • Cardiology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Vascular Medicine (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Inorganic Chemistry (AREA)
  • Dentistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Materials For Medical Uses (AREA)

Abstract

Acide hyaluronique sous forme réticulée ou dans un mélange de gel contenant une forme réticulée et une forme non réticulée pour guérir et/ou régénérer des os et du tissu entourant les os, chez l'homme ou un vertébré, par injection du gel contenant l'acide hyaluronique dans le périoste d'un os.
EP16750610.4A 2015-07-19 2016-07-18 Nouvelle utilisation d'acide hyaluronique Withdrawn EP3324981A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102015009271.5A DE102015009271A1 (de) 2015-07-19 2015-07-19 Neue Verwendung von Hyaluronsäure
PCT/EP2016/001253 WO2017012711A1 (fr) 2015-07-19 2016-07-18 Nouvelle utilisation d'acide hyaluronique

Publications (1)

Publication Number Publication Date
EP3324981A1 true EP3324981A1 (fr) 2018-05-30

Family

ID=56683880

Family Applications (1)

Application Number Title Priority Date Filing Date
EP16750610.4A Withdrawn EP3324981A1 (fr) 2015-07-19 2016-07-18 Nouvelle utilisation d'acide hyaluronique

Country Status (4)

Country Link
US (1) US10449214B2 (fr)
EP (1) EP3324981A1 (fr)
DE (1) DE102015009271A1 (fr)
WO (1) WO2017012711A1 (fr)

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002504083A (ja) 1996-03-05 2002-02-05 オーケスト インコーポレイテッド ヒアルロン酸および増殖因子による骨の増殖を促進する方法
FR2865737B1 (fr) * 2004-02-03 2006-03-31 Anteis Sa Gel reticule biocompatible
US20050226936A1 (en) * 2004-04-08 2005-10-13 Q-Med Ab Method of soft tissue augmentation
EP2647649A1 (fr) * 2012-04-04 2013-10-09 Andreas Witt Gel d'acide hyaluronique, procédé de fabrication de ce gel et produit médical contenant ce gel
WO2014138897A1 (fr) * 2013-03-14 2014-09-18 Anacoti Ltd. Dérivés d'acide hyaluronique

Also Published As

Publication number Publication date
WO2017012711A1 (fr) 2017-01-26
US20180207199A1 (en) 2018-07-26
DE102015009271A1 (de) 2017-01-19
US10449214B2 (en) 2019-10-22

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