EP2459162A2 - Injizierbare zusammensetzung mit einer kombination aus einem füller und einem fibroblastenwachstumsmedium - Google Patents

Injizierbare zusammensetzung mit einer kombination aus einem füller und einem fibroblastenwachstumsmedium

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Publication number
EP2459162A2
EP2459162A2 EP10742206A EP10742206A EP2459162A2 EP 2459162 A2 EP2459162 A2 EP 2459162A2 EP 10742206 A EP10742206 A EP 10742206A EP 10742206 A EP10742206 A EP 10742206A EP 2459162 A2 EP2459162 A2 EP 2459162A2
Authority
EP
European Patent Office
Prior art keywords
composition according
fibroblast growth
composition
growth medium
skin
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Withdrawn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
EP10742206A
Other languages
English (en)
French (fr)
Inventor
Jean-Noël THOREL
Hugues Gatto
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
Priority to EP13198504.6A priority Critical patent/EP2727581B1/de
Publication of EP2459162A2 publication Critical patent/EP2459162A2/de
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
    • 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
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • 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
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A61K8/673—Vitamin B group
    • A61K8/675—Vitamin B3 or vitamin B3 active, e.g. nicotinamide, nicotinic acid, nicotinyl aldehyde
    • 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
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/20—Polysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/52—Hydrogels or hydrocolloids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/91—Injection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/06—Flowable or injectable implant compositions

Definitions

  • the present invention is part of the development of injectable solutions for the treatment of wrinkles.
  • the skin is a continuously renewed tissue comprising a plurality of cells and specialized structures. Because of its constant contact with the environment, the skin is a protective barrier for the body. In addition, it is involved in many physiological processes that allow the body to maintain a fixed and constant temperature. In addition, the skin plays an important role in the immune system that protects the body from disease. At the structural level, the skin has three layers:
  • epidermis an outer layer, called epidermis
  • subcutaneous tissue an inner layer, called subcutaneous tissue
  • the natural human epidermis is composed mainly of three types of cells, namely the very major keratinocytes, melanocytes and Langerhans cells.
  • the epidermis as an outer layer, acts as a barrier against external agents.
  • the epidermis itself comprises 5 distinct layers, from the depth to the surface: the basal layer or stratum germinativum,
  • the dermis provides the epidemic with a solid support and acts as a nurturing element vis-à-vis the epidermis.
  • the dermis consists essentially of fibroblasts and an extracellular matrix (ECM), which is mainly composed of collagen, elastin and a substance called the "fundamental substance". All of these components are synthesized by the fibroblasts.
  • ECM extracellular matrix
  • Leukocytes, hematocytes or tissue macrophages are also found in the dermis. In addition, it is crossed by blood vessels and nerve fibers.
  • subcutaneous tissue or hypodermis is a layer of adipose and connective tissue that covers the nerves and large blood vessels.
  • the main signs of aging skin include the appearance of fine lines and / or wrinkles, increasing with age. These wrinkles can be deep, medium or superficial and particularly affect the nasolabial folds, the periorbital area, the contour of the lips, the forehead, the intersurillary zone (lion's wrinkles). These lines and wrinkles result in depression or furrows on the surface of the skin.
  • Deep wrinkles are due to dermo-hypodermic changes, while superficial wrinkles can be explained by dermal and possibly epidermal changes. Wrinkles are often due to the loss of elasticity of the skin, in particular a relaxation of the tissues, as well as the production of fine lines of different thicknesses. When the dermis loses its elasticity, it weakens and begins to form deeper wrinkles. During the production of wrinkles, the collagen fibers, responsible for the elasticity and the structure of the skin, lose their characteristics, with an overproduction of metalloproteinase type enzymes. This abnormal amount of enzymes degrades the collagen matrix and thus leads to the production of deep wrinkles. Thus, over the years, the dermis tends to become thinner, especially at the level of its collagen layer. Other factors, such as free radicals, sun exposure, pollution, smoking, alcohol consumption or ozone, can cause damage to the skin, through the same phenomenon of activation of metalloproteinases and decomposition of collagen.
  • botulinum toxin deactivated Botox ®
  • laser techniques or their use in combination.
  • hyaluronic acid is a preferred compound.
  • hyaluronic acid is a natural constituent of the dermis, where it plays an important role in the hydration and elasticity of the skin. he however decreases in quantity and quality with age, resulting in drying and thinning of the skin that wrinkles. Since hyaluronic acid is also highly hydrous and forms solutions with high viscosity in water, it is one of the most widely used pharmaceutical products.
  • hyaluronic acid used in pharmaceutical products or medical devices for the treatment of wrinkles is in the form of a sodium or potassium hyaluronate gel.
  • sodium or potassium hyaluronate gels have a fairly rapid bioresorbability (typically ranging between 4 and 6 months), which requires that injections be repeated at close and regular intervals.
  • HA hyaluronic acid
  • these are chemically crosslinked HA gels. This crosslinking, via intramolecular or intermolecular bridging, would increase the persistence of the product inside the dermis.
  • hyaluronic acid WO2008 / 147817
  • the Claimant has entered a totally new approach. While the prior art advocated associating a filler, such as hyaluronic acid, with a protective agent thereof, the present invention proposes acting at two distinct levels to restore good skin appearance. , especially to fight against aging.
  • the present invention relates to a composition (dermatological, cosmetic or therapeutic) injectable, combining both a so-called mechanical filler, known as such, and secondly, a fibroblast growth medium.
  • a so-called mechanical filler known as such
  • a fibroblast growth medium In practice, it is therefore both to act physically to fill the asperities or furrows that constitute wrinkles and secondly to stimulate the growth of fibroblasts in the dermis. Fibroblasts can also grow inside furrows and in addition synthesize substances such as elastin and collagens that promote regeneration of the dermis.
  • the growth medium is capable of stabilizing and protecting the filling agent in the presence.
  • the first component of the combination according to the invention is therefore a mechanical filler whose essential function is to create a volume inside the wrinkles.
  • hyaluronic acid can be in various forms: salts, derivatives such as esters or amides, in linear form or crosslinked chemically. All these forms are conceivable in the context of the present invention. While crosslinking can increase the life of hyaluronic acid molecules in the body, these changes affect its physico-chemical characteristics, its biological properties and its potential immunogenicity.
  • biomimetic non-crosslinked hyaluronic acid, as well as its physio-logically acceptable salts, is therefore preferred insofar as this molecule is a natural constituent of dermis.
  • physiologically acceptable salts of hyaluronic acid especially the sodium and potassium salts, and their mixture.
  • the filler advantageously hyaluronic acid
  • the filler represents from 0.07 to 3% of the total weight of the composition, advantageously from 0.8 to 2.5%.
  • degree of crosslinking and the molecular weight of the hyaluronic acid chosen may depend on the intended application, in particular on the depth of the wrinkles to be treated.
  • the second necessary component of the composition according to the invention is therefore a fibroblast growth medium.
  • a fibroblast growth medium is defined as a complete medium allowing not only maintenance of the fibroblasts alive, but also stimulating their multiplication.
  • the implementation of a functional growth test makes it possible to determine whether a given medium corresponds to a fibroblast growth medium according to the invention.
  • a suitable functional test well known to those skilled in the art is the test for the observation of the density of living cells by colorimetric method, using the WST-I reagent and a reading at 450 nm (Berridge, MV et al.
  • a fibroblast growth medium is for example commercially available: it is the standard culture medium DMEM (Sigma) supplemented with cell growth factor SVF (fetal calf serum), at a level of 10% by weight.
  • DMEM standard culture medium
  • SVF cell growth factor
  • such media contain extracts of animal or cellular origin which have a stimulating effect on the growth of fibroblasts, but which have the drawback of not having a specific composition or of containing non-traceable exogenous elements.
  • FCS beef pituitary stem extracts
  • EGF epidermal growth factor
  • FGF fibroblast growth factors
  • insulin or cholera toxin hydrocortisone
  • piperazine ...
  • the fibroblast growth medium used in the context of the present invention does not contain cell growth factor or biological extract of animal or cellular origin, in particular if these are not traced. or traceable and / or not of definite composition.
  • non-traced or “non-traceable” means that the source of the biological material in question and / or the treatment to which it is subjected can not be established or controlled.
  • said medium is advantageously devoid of (free) biological extract of animal or cellular origin, cell growth factor or compound, or a hormone.
  • a fibroblast growth medium as compatible as possible with the natural composition of the skin, namely a medium comprising biodermal constituents (contained in the invention).
  • a medium comprising biodermal constituents obtained in the invention.
  • biodermal constituents obtained in the invention.
  • natural state in the skin biomimetic and / or biocompatible (biological elements mimetic or neutral for the skin).
  • Such a medium makes it possible to provide the fibroblasts with optimized nutritional intake in the form of vitamins, trace elements, amino acids, mineral salts, simple sugars (such as glucose, ribose, deoxyribose) and / or complex (such as than HA), and natural growth factors in the form of nucleic acid constituents (nitrogenous and pentose bases required for the formation nucleotides, as well as nucleosides). It also advantageously has pH characteristics (between 6.5 and 7.9, advantageously between 7.4 and 7.6 and osmolarity (between 280 and 450 mOsm, advantageously between 300 and 350 mOsm) physiological.
  • HA can be both an ingredient of the growth medium and a filler. The difference lies both in the form of HA (necessarily a hyaluronate salt in the medium) and in its quantity (much lower amounts in the medium).
  • all the constituents of the medium are naturally present in the skin (dermal constituents).
  • a medium can be enriched with a substance exogenous to the skin but of natural origin, traceable and well-defined composition.
  • a substance corresponding to this definition is, for example, a mixture of peptides extracted from milk, or MPC complex ("MiIk Peptide Complex"), obtained by successive precipitations of the milk and then separation of certain proteins subjected to enzymatic hydrolysis.
  • MPC complex MPC complex
  • This substance which is in the form of a dehydrated powder, is advantageously added to the medium in an amount of 0.5 to 5 mg / ml, and even more advantageously in the range of 4 to 5 mg / ml.
  • the fibroblast growth medium used in the composition according to the invention is devoid of EDTA and its salts and / or lipoic acid as metalloproteinase inhibiting agents.
  • a composition according to the invention may further contain other ingredients or excipients, commonly used in this application, including derivatives or purified fractions of the HA.
  • the injectable composition comprises only the two components described above.
  • this composition is intended to be injected and is therefore comparable to an injectable implant.
  • the implant according to the present invention is therefore intended to be injected into the superficial, medium or deep dermis, subcutaneously or intradermally, advantageously at the level of the face.
  • the composition is in the form of a gel, because of the injectable application subject of the invention.
  • this constraint is fully compatible with the fibroblast growth media described above, which is formable in gel form, by incorporating HA without the addition of exogenous excipients.
  • the composition is in the form of a monophasic hydrogel, namely a hydrogel in the form of a single homogeneous phase.
  • the viscosity of the composition obtained can be easily adjusted, in particular by adjusting the composition and the amount of the filler.
  • hyaluronic acid one can play both on the concentration which typically varies between 0.07% and 3% by weight of the composition, but also in terms of its degree of crosslinking or its molecular weight.
  • the injectable composition according to the invention may also be the subject of a kit which further comprises syringes that may contain said composition.
  • syringes that may contain said composition.
  • This is for example single-dose syringes of 0.5 to 1.5 ml.
  • the 2 essential components of the composition may be presented as a mixture in one syringe, or in 2 separate syringes for extemporaneous mixing.
  • such a composition is advantageously subjected to sterilization, sterilization taking place advantageously cold so as not to denature the components in the presence.
  • This step may, for example, be carried out by filtration on a 0.22 ⁇ m membrane for the growth medium of the fibroblasts, and by separate sterilization according to a process known to those skilled in the art for HA.
  • the two constituents of the composition according to the invention can be administered simultaneously, separately or spread over time.
  • a composition according to the invention is intended to correct all cutaneous irregularities, and in particular to the treatment, improvement and / or prevention of skin aging. This includes wrinkles, fine lines, fibroblastic depressions and scars, especially in the areas of the face or forehead marked by expression lines.
  • a composition according to the invention relates both to dermatology and to reconstructive surgery.
  • the present invention relates to a cosmetic or therapeutic treatment method of injecting the composition defined in the present application.
  • the mixture of the two essential constituents of this composition can be done extemporaneously. Likewise, their injection can take place in a non-simultaneous manner.
  • composition according to the present invention two complementary physiological actions are therefore targeted and obtained: on the one hand a mechanical action of filling irregularities, but also the action of promoting cellular renewal and, in fact, the synthesis of constituents neo-synthesized by fibroblasts, including collagen and elastin. This results in a remodeling of the extracellular matrix and a revitalization of the dermis.
  • such a composition is completely biocompatible with the skin, insofar as it consists essentially of constituents naturally present in the dermis. In fact, it does not disturb the microenvironment of the skin, thus reducing the risk of inflammatory or allergic reactions.
  • biomimetic and biocompatible media allow stimulated fibroblast growth in the presence of serum. They are therefore particularly suitable candidates in the context of a dermal injection, since the dermis is richly vascularized.
  • FIG. 1 illustrates the comparative growth of human fibroblasts in culture in a fibroblast growth medium according to the invention and the standard medium.
  • DMEM DMEM (sigma), without growth factor.
  • FIG. 2 represents the collagen levels in the superficial and middle dermis of healthy skin, altered by UV radiation and after treatment with a fibroblast growth medium according to the invention.
  • Figure 3 corresponds to histological sections showing the marking of collagen fibers in healthy skin, altered by irradiation and after treatment with a fibroblast growth medium according to the invention.
  • FIG. 4 illustrates the dosage of elastin in healthy skins, then modified by UV radiation and then after treatment with the fibroblast growth medium according to the invention.
  • Figure 5 corresponds to histological sections showing the labeling of elastin fibers in healthy skin, skin altered by irradiation and then treated with the fibroblast growth medium according to the invention.
  • FIG. 6 represents the GAG levels in the superficial and middle dermis of healthy skin, skin damaged by UV radiation and after treatment with the fibroblast growth medium according to the invention.
  • Figure 7 corresponds to histological sections showing the labeling of GAGS in healthy skin, skin altered by UV irradiation and after treatment with the fibroblast growth medium according to the invention. Examples of realization
  • the culture medium according to the invention supports, alone, the growth of fibroblasts over a period of 9 days. From the 7th day, a slowing down of cell growth is observed, explained by the non-renewal of the medium (Fig. 1).
  • Medium according to the invention added to the surface of the skin from D3 to D14 (imbibed paper).
  • Collagen (Sirius Red) and elastic fibers (Catechin)>% surface area occupied at the level of the superficial and average dermis (computer-assisted image analysis).
  • GAGs Glycosaminoglycans
  • semiquantitative score intensity of the staining
  • Total collagen on skin fragments after enzymatic digestion and grinding.
  • GAGs on fragments of ground skin.
  • This model made it possible to quantify, on histological sections, the connective tissue repair properties of the fibroblast growth medium used.
  • this medium stimulates the repair and restoration of essential components of the dermis (collagen fibers, elastin, GAGs) during tissue alterations.
  • HA added up to 3% by weight of the total composition, with preferentially: 0.8% for the treatment of superficial wrinkles, 1.6% for the treatment of middle wrinkles and 2% for the treatment of deep wrinkles .
  • Formulation of a gel HA is dissolved in the fibroblast culture medium. The concentration of HA determines the viscosity of the final preparation.
  • the HA used is sodium hyaluronate, the molecular weight of which is between 1.3 and 1.8 MDa.
  • the injectable gel according to the invention does not contain any additive, all of the components of the formula acting both as excipients and active ingredients.
  • Sterilization by 0.22 ⁇ m membrane filtration for the fibroblast growth medium, and by separate sterilization according to a process known to those skilled in the art for HA.
  • Injection protocol Depending on the area to be treated and the depth of the wrinkles one or more sessions are envisaged. To maintain the results, it may be necessary to perform biannual retouching, the filling of wrinkles for as long as the skin is younger.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Dermatology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Transplantation (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Birds (AREA)
  • Inorganic Chemistry (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Dispersion Chemistry (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Cosmetics (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Polymers & Plastics (AREA)
EP10742206A 2009-07-27 2010-07-06 Injizierbare zusammensetzung mit einer kombination aus einem füller und einem fibroblastenwachstumsmedium Withdrawn EP2459162A2 (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP13198504.6A EP2727581B1 (de) 2009-07-27 2010-07-06 Injizierbare zusammensetzung mit einer kombination aus einer füllsubstanz und einem fibroblastenwachstumsmedium

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0955235A FR2948286B1 (fr) 2009-07-27 2009-07-27 Composition injectable associant un agent de comblement et un milieu de croissance des fibroblastes
PCT/FR2010/051421 WO2011015744A2 (fr) 2009-07-27 2010-07-06 Composition injectable associant un agent de comblement et un milieu de croissance des fibroblastes

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Publications (1)

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EP2459162A2 true EP2459162A2 (de) 2012-06-06

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EP10742206A Withdrawn EP2459162A2 (de) 2009-07-27 2010-07-06 Injizierbare zusammensetzung mit einer kombination aus einem füller und einem fibroblastenwachstumsmedium
EP13198504.6A Active EP2727581B1 (de) 2009-07-27 2010-07-06 Injizierbare zusammensetzung mit einer kombination aus einer füllsubstanz und einem fibroblastenwachstumsmedium

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Country Link
US (1) US9339450B2 (de)
EP (2) EP2459162A2 (de)
JP (1) JP5735965B2 (de)
KR (1) KR101779905B1 (de)
BR (1) BR112012001497B1 (de)
ES (1) ES2648391T3 (de)
FR (1) FR2948286B1 (de)
WO (1) WO2011015744A2 (de)

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FR2979539B1 (fr) * 2011-09-05 2013-09-27 Teoxane Composition sterile dermo-injectable
TWI466675B (zh) 2011-09-16 2015-01-01 Univ China Medical 用於抑制發炎之醫藥組合物
US20150216781A1 (en) 2012-07-18 2015-08-06 Sebastien Pierre Hyaluronic acid formulation containing pyruvate
CN102973495A (zh) * 2012-11-15 2013-03-20 上海景峰制药股份有限公司 一种减缓玻璃酸钠在体内降解的方法
BE1022012B1 (fr) * 2013-04-26 2016-02-04 Auriga International Gel stable d'acide hyaluronique et d'une forme libre de vitamine c et/ou de l'un de ses sels
US9597271B2 (en) 2013-10-24 2017-03-21 The Procter & Gamble Company Cosmetic compositions and methods
US9226890B1 (en) 2013-12-10 2016-01-05 Englewood Lab, Llc Polysilicone base for scar treatment
SG11201704423SA (en) * 2014-12-04 2017-06-29 Professional Dietetics Spa Aminoacid-based composition for fibroelastin recovery in dermal connective tissues
US11013678B2 (en) 2015-06-29 2021-05-25 The Procter & Gamble Company Multi-component skin care product
RU2697671C1 (ru) * 2015-11-24 2019-08-16 БиЭмАй КОРЕЯ КО., ЛТД Композиция для инъекций гиалуроновой кислоты, содержащей производное гиалуроновой кислоты и ДНК фракцию, и ее применение
US10918585B2 (en) 2015-12-22 2021-02-16 Showa Denko K.K. Anti-aging agent and anti-aging composition for skin
CN108430449B (zh) 2016-01-11 2023-01-24 宝洁公司 处理皮肤状况的方法以及用于其的组合物
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JP5735965B2 (ja) 2015-06-17
CN102497851A (zh) 2012-06-13
KR20120089433A (ko) 2012-08-10
JP2013500315A (ja) 2013-01-07
EP2727581B1 (de) 2017-11-15
US20120121534A1 (en) 2012-05-17
FR2948286B1 (fr) 2011-08-26
FR2948286A1 (fr) 2011-01-28
ES2648391T3 (es) 2018-01-02
BR112012001497B1 (pt) 2022-04-26
EP2727581A1 (de) 2014-05-07
US9339450B2 (en) 2016-05-17
WO2011015744A2 (fr) 2011-02-10
WO2011015744A3 (fr) 2011-12-08
KR101779905B1 (ko) 2017-09-19
BR112012001497A2 (pt) 2019-09-24

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