WO1989007117A1 - Hydrogels de polyurethane thermiquement reversibles et leurs applications cosmetiques, biologiques et medicales - Google Patents

Hydrogels de polyurethane thermiquement reversibles et leurs applications cosmetiques, biologiques et medicales Download PDF

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Publication number
WO1989007117A1
WO1989007117A1 PCT/US1988/000280 US8800280W WO8907117A1 WO 1989007117 A1 WO1989007117 A1 WO 1989007117A1 US 8800280 W US8800280 W US 8800280W WO 8907117 A1 WO8907117 A1 WO 8907117A1
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Prior art keywords
glycol
hydrogel
weight
diisocyanate
mixture
Prior art date
Application number
PCT/US1988/000280
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English (en)
Inventor
Francis E. Gould
Christian W. Johnston
George E. Seems
Original Assignee
Tyndale Plains-Hunter, Ltd.
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 Tyndale Plains-Hunter, Ltd. filed Critical Tyndale Plains-Hunter, Ltd.
Priority to EP19880902003 priority Critical patent/EP0401210A4/en
Priority to PCT/US1988/000280 priority patent/WO1989007117A1/fr
Publication of WO1989007117A1 publication Critical patent/WO1989007117A1/fr

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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
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04—Dispersions; Emulsions
    • A61K8/042—Gels
    • 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
    • A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
    • A61K8/87—Polyurethanes
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • 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
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0019—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A61L26/008—Hydrogels or hydrocolloids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q13/00—Formulations or additives for perfume preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q15/00—Anti-perspirants or body deodorants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • 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
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/40—High-molecular-weight compounds
    • C08G18/48—Polyethers
    • C08G18/4833—Polyethers containing oxyethylene units
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/65—Low-molecular-weight compounds having active hydrogen with high-molecular-weight compounds having active hydrogen
    • C08G18/66—Compounds of groups C08G18/42, C08G18/48, or C08G18/52
    • C08G18/6666—Compounds of group C08G18/48 or C08G18/52
    • C08G18/667—Compounds of group C08G18/48 or C08G18/52 with compounds of group C08G18/32 or polyamines of C08G18/38
    • C08G18/6674—Compounds of group C08G18/48 or C08G18/52 with compounds of group C08G18/32 or polyamines of C08G18/38 with compounds of group C08G18/3203
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
    • C08G18/72—Polyisocyanates or polyisothiocyanates
    • C08G18/74—Polyisocyanates or polyisothiocyanates cyclic
    • C08G18/75—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic
    • C08G18/758—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing two or more cycloaliphatic rings
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G2210/00—Compositions for preparing hydrogels

Definitions

  • This invention relates to thermally reversi ⁇ ble hydrogels and, in particular, to thermally rever ⁇ sible hydrogels produced from certain hydrophilic polyurethane polymers.
  • the invention is also con ⁇ cerned with cosmetic, biological and medical applica- tions of the polyurethane hydrogels such as carrier and delivery systems for active agents, including 1 iving cells.
  • U.S. Patent Nos.3,822,238 and 3,975,350 describe an active agent carrier system comprising an active agent and as a carrier vehicle therefor, a hydrophilic, preferably cross-linked polyurethane pol ⁇ ymer.
  • the carrier system is utilized by subjecting it to aqueous conditions whereby the polyurethane carrier undergoes hydration and swelling with concomitant formation of an insoluble hydrogel from which the active agent is leached out by and into the aqueous medium.
  • the rate and duration of release can be controlled by employing a carrier polymer of the req- uisite water absorptivity.
  • poly ⁇ urethane polymers prepared from water soluble active hydrogen resins will exhibit the highest water absorptivity.
  • Polymers having diminished water absorptivity can be produced from less soluble resins, or by cross- linking.
  • the carrier system aforesaid is useful as a means for delivering various active agents, such as medicinal or cosmetic agents, to a treatment zone.
  • shaped articles made of the carrier system can be inserted into the body to provide preci ⁇ sion administering of drugs or serums over extended periods of time.
  • hydrophilic polyurethanes that form insoluble hydrogels in the hydrated state is disclosed in U.S. Patent Nos. 4,156,066 and 4,156,067. These polyurethanes are characerized by the presence of lactone groups in the polymer backbone. The lac- tone may be opened by hydrolytic cleavage to form carboxylic acid groups which render the polymer sol ⁇ uble in al kali ne medium.
  • Other specialized hydrophil- ic polyurethanes are the polyurethane diacrylates of
  • the active agent carrier vehicle of the invention is a thermally reversible hydrogel compri ⁇ sing water and a gel-forming, hydrophilic polyurethane polymer which is produced by reacting under anhydrous conditions an organic diisocyanate with a glycol com ⁇ ponent comprising a polyoxye thy lene glycol or mixture of glycol s in an NCO/OH weight ratio of from about 0.5/1 to about 1/1 and wherein the percentage by weight of the diisocyanate in the anhydrous reaction mixture exclusive of catalyst is from about 2% to about 25%, preferably from about 5% to about 17%.
  • Anhydrous as used in this specification means that the reaction mixture is sufficiently free of water so that the polymer product will be thermally reversible between a gel state and a sol state as further described below.
  • Anhydrous conditions may be produced in any known manner of providing a dry reac ⁇ tion environment. Typical drying procedures include subjecting reactants to heat, vacuum, azeotropic dis ⁇ tillation or contact with dessi eating agents. Drying of the glycol component is especially important since glycols commonly contain residual moisture, often in amounts sufficient to deleteriously affect the proper- ties of the herein gel compositions. The dried gly ⁇ cols, which tend to be hygroscopic, should be protec ⁇ ted from atmospheric moisture. Other reactants, i.e., isocyanates and catalysts, can ordinarily be used without drying, owing to their lack or near lack of associated moisture. Precautions should also be taken to ensure that all reaction vessels and apparatus are free of moisture.
  • the polyurethane polymer compo ⁇ nent preferably granulated or in small pieces, is added to an aqueous medium such as water or an aqueous solution.
  • an aqueous medium such as water or an aqueous solution.
  • the resulting mixture is allowed to stand until the polymer undergoes hydration and concomitant swelling. This generally takes about one to four hours, depending on the particular polymer and its state of subdivision.
  • the aqueous medium containing the swollen polymer is then heated at mildly elevated temperatures with vigorous agitation.
  • the heating is conducted at temperatures of from about 37 °C to about
  • the polymer is gradually assimilated into the aqueous medium. At this point, heating and stirring are discontinued.
  • the resulting liquid may be described as the sol state of the thermally reversible hydrogels of the invention. No necessary limitation to colloidal character is intended, however, since the sol state of the polymer in some respects appears to behave more like a true solution than a colloidal dispersion.
  • the assimila- tion of the polyurethane polymer into the aqueous medium involves both dissolution and dispersion of the polymer. As the temperature of the sol is lowered, it is believed that aggregation of the polymer particles occurs with ensuing reversion to the gel state. But whatever the mechanism of the sol/gel transition, the aqueous polyurethane polymers of the invention consti ⁇ tute a thermally reversible sol/hydrogel-type system.
  • the temperature at which the sol reverts to the gel and vice versa will depend on the particular polyurethane polymer and its concentration in the aqueous medium. Hydrogels have been obtained after equilibration in which the sol/gel transition occurs in the temperature region of about 30°C to about 45°C in general, the concentration by weight of the polymer component in the hydrogel is about 1% to about 15%, preferably about 3% to about 7%.
  • the polyurethane polymer used in forming the thermally reversible hydrogels of the invention is prepared by the reaction of the diisocyanate and gly ⁇ col component (s) in the presence of a catalyst for the polyurethane reaction.
  • Suitable catalysts include tin salts; organic tin esters as exemplified by dibutyl tin dilaurate; tertiary amines of which triethyl di ⁇ amine (DABCO) and N,N,N * ,N'-tetramethyl-l,3 butane diamine are representative, as well as other known catalysts for such reaction.
  • the glycol component is freed of moisture prior to reacting it with the diiso ⁇ cyanate. Drying is conveniently effected by heating the glycol component i vacuo (8 mm of Hg or less absolute) at mildly elevated temperatures, typically about 50°C to about 70°C.
  • the moisture-free glycol component, diisocyanate and catalyst are brought together at about room tempera ⁇ ture or slightly higher but usually not above about 60°C. Where more than one glycol is used, these are preferably formed into a homogeneous mixture or melt before reacting with the diisocyanate. Following mixing of the glycol and diisocyanate components in the presence of the catalyst, a mildly exothermic reaction occurs, the temperature rising to about 50°C
  • Representative commercial polyoxyethylene glycols are CARBCWAX 0 1450, CARBOWAX* 4500 and CARBOWAX* 8000 in which the numbers refers to number average molecular weights. These products are manu ⁇ factured by union Carbide Corporation.
  • diisocyanates are methyl ene- bis(cyclohexy 1-4 ,4 '-isocyanate) , trimethyl hexameth- ylene diisocyanate, isophorone diisocyanate, cyclohex- yl diisocyanate and dissocyanate precursors or equiva- lents such as the nitrile carbonates, e.g., the adipo- nitril e carbonate of the formul a:
  • the mol ecul ar weight (in the case of glycol s, hereinafter number av erage mol ecul ar weight) of the glycol component such as polyoxyethyl ene glycol must be such that the stated diisocyanate percentage and NCO/OH mole ratio is pre ⁇ served in the reaction mixture.
  • the glycol will have a molecular weight that is about 9 times the molecular weight of the diisocya ⁇ nate.
  • the diisocyanate aforesaid is methyl ene- bis(cycl ohexy 1-4,4 '-isocyanate) , which has a molecular weight of 260, then the molecular weight of the glycol will be 9 times 260 or 2340. Glycol molecular weights for other diisocyanate percentages and NCO/OH mole ratios are computed in like manner.
  • the glycol component is a blend of a lower polyoxyethylene glycol (sometimes referred to as an "alkylene glycol") with a higher member in which the average molecular weight of the glycol blend satisfies the NCO/OH ratio and diisocyanate percen ⁇ tage.
  • a glycol blend consisting of 1 mole each of CARBOWAX* 1450 and diethylene glycol M.W. 106.12 would have an average molecular weight of (1450 + 106.12/2) or 77 ⁇ * Average molecular weights for other mole ratios of glycol ⁇ are computed similarly.
  • the glycol blend will contain a lower alkylene glycol such as diethylene or triethylene glycol and a higher polyoxyethylene glycol having an average molec ⁇ ular weight up to about 10,000.
  • An especially pre ⁇ ferred glycol blend is a mixture of up to about 95% diethylene glycol and up to about 5% of one or more polyo ye thy lene glycols having an average molecular weight in the range of from about 1450 to about 8000.
  • the thermally reversible hydrogels of the invention provide a highly effective means for the protection, controlled delivery and sustained release of an active agent.
  • the hydrogel is melted to the liquid state and the active agent is mixed with the liquid. The temperature of the mixture is then lowered to promote gelling. The active agent is thereby encapsulated in the gel matrix and thus immobilized and protected.
  • the active material is rendered mobile in the fluidized hydrogel for delivery and application to the treatment area at a rate dependent on its concentration in the gel, the rate at which the gel melts, and other fac ⁇ tors such as the environment in which melting occurs.
  • Active agents may also be first dispersed in an aque ⁇ ous medium used to form the gel state of the polyure ⁇ thane, thereby being incorporated into the hydrogel during formation thereof.
  • the mechanism whereby the active agent is released from the hydrogel of the invention differs in its mode of operation as compared to leaching of the active agent from the water insoluble, water swell able polyurethane polymers of the cited patents.
  • active agents which can be applied singly or in combination by means of the polyurethane hydrogels of the invention, are phar a- ceuticals including anti-cancer drugs; agrichemicals including pesticides of all types such as bacterio- cides, viricides, insecticides, herbicides, larva- cides, fungicides, algaecides and nematocides; topical or dermatological agents such as deodorants, cos- metics, protective screens such as ultraviolet skin coatings, moisturizers and the like; and a host of other substances such as salts, pH regulators, hor ⁇ mones, enzymes and other proteinaceous substances, fragrances, deodorants, humectants, antioxidants, pre- servatives, and food additives such as flavors, essen ⁇ ces and spices.
  • agrichemicals including pesticides of all types such as bacterio- cides, viricides, insecticides, herbicides, larva- cides, fungicides
  • the hydrogels are also useful as non- toxic culture media for the growth of microorganisms and as gel matrices for the immobilization of enzymes, bac ⁇ terial cells or other microorganisms in carrying out fermentation reactions such as the manufacture of citric acid.
  • living cells is intended to mean and include individual animal and plant cells as well as cell clusters, tissues, organs and organisms including microorganisms such as bacteria, molds and fungi.
  • the hydrogels of the invention can also function as non- toxic media for electrophoretic separation of bio ⁇ logical substances such as enzymes, viruses, proteins and nucleic acids in accordance with well known tech ⁇ niques.
  • the hydrogels are useful in a method developed for the treatment of tumors.
  • the thermally reversible polyurethane in gel form and containing an anti-cancer drug is applied to or at the site of a tumor.
  • the tumor is then subjected to a source of radiant heat such as a diathermy machine.
  • a source of radiant heat such as a diathermy machine.
  • the temperature of the tumor reaches the point at which the gel becomes fluid, the entrapped drug is released and brought into contact with the tumor.
  • hydro ⁇ gels are substituted for or used in addition to the gelatinous substances commonly present in such formu- lations.
  • a polyether moiety is prepared by mixing 81.4 parts of CARBOWAX # 4500 polyoxyethylene glycol
  • the reaction mass is then poured into a polypropyl ene pan. During pouring, the temperature of the mass continues to rise and, as the temperature approaches 80 ° C, the mass foams. Upon compl etion of the pouring operation, the pan is pl aced in an air circulating oven at 100 ° C and maintained in the oven for one hour to cure the polymer.
  • the polymer mass i s cut i nto smal l pi eces.
  • a suf f i ⁇ cient amount of the small pieces is mixed with water to form a mixture containing 12% sol ids.
  • the mixture is stirred whil e increasing the temperature of the mixture to 95 °C With continued stirring, the mass begins to homogeniz e and then thickens.
  • the mass Upon cooling to 55 °C, the mass sets into a highly viscous gel.
  • l ower solids concentration hydrogel s may be formed by dil ution with water or with an aqueous culture medium. For storage purposes, the hydrogel may be dri ed.
  • Hydrogel s of any desired sol ids content and of any desired aqueous consistency may be prepared by mixing the required amount of the dry polymer with water and/or an aqueous medium such as a culture medium, and heating the mixture to about 40 °C with stirring.
  • a hydrogel containing 5% of the above- described polymer with an aqueous culture medium is in its sol state, i.e., a flowable, somewhat syrupy liq ⁇ uid at 37 °C But when cooled to room temperature (20°C - 22°C), the mixture sets into a solid gel and thus can be used as an agar substitute for the cultur- ing of cells and organisms.
  • the liquid hydrogel may be brought to the desired pH for specific cells or microorganisms (such as ⁇ . coli) by the addition of a buffer solution or a dilute acid or alkaline solution.
  • the temperature of the polymer- saline system is slowly raised to 75°C to 76°C under vigorous stirring.
  • the polymer dissolves and forms a homogeneous solution.
  • the solution is slowly cooled under constant stirring to 35 °C to 36 °C, when the stirring is discontinued and the mixture allowed to gel.
  • the gel remains solid at temperatures up to 37°C to 38°C, even in water or physiological saline, and releases the entrapped drug only slowly. When heated to 45°C, the gel melts and releases the en- trapped drug rapidly.
  • it is suitable as a carrier for anti-cancer and other drugs, which can be placed at the tumor site or a site of infection and released during hyperthermia; that is, when the site is overheated to 45 °C
  • T j catalyst 0.15 part of T j catalyst is added under con ⁇ stant stirring. The mixture starts to exotherm. When the temperature reaches 70°C, stirring is discontinued and the mixture poured into a polypropylene tray. The tray is placed in a circulating oven and the mixture cured for one hour at 100°C
  • the solid block of polymer is granulated to 1/ 4-inch particles.
  • a gel is prepared therefrom con- taining 25% solids, following the procedure of Example
  • the solvent in this case is 85 parts of distilled water and 15 parts of SDA ethyl alcohol.
  • the gel has a viscosity of 1,200 cP at 25°C, and is used for preparation of face masks, wrinkle creams and as a base for mascara.
  • a gel is prepared from 5 parts of the poly ⁇ mer and 95 parts of water, following the procedure described in Example 1.
  • the gel is easily spreadable on the skin, where it forms an invisible, nongreasy and nontacky film, usable as skin protection for dry skin, psoriasis, etc.
  • the film is easily removed with warm water.

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Abstract

On forme des hydrogels de polyuréthane thermiquement réversibles en ajoutant de l'eau à un polymère de polyuréthane hydrophile formant un gel, produit par réaction dans des conditions anhydres d'un diisocyanate organique avec un composant glycol, dans un rapport molaire NCO/OH d'environ 0,5/1 à environ 1/1, dans lequel le pourcentage en poids du diisocyanate dans le mélange de réaction est d'environ 2 % à environ 25 %. Les hydrogels sont solides à température ambiante mais se liquéfient à des températures supérieures telles que la température du corps, et par conséquent sont utiles comme supports de protection, d'administration et de libération étalée d'une variété d'agents actifs comprenant des produits pharmaceutiques, des cosmétiques, des cellules et organismes vivants.
PCT/US1988/000280 1988-02-01 1988-02-01 Hydrogels de polyurethane thermiquement reversibles et leurs applications cosmetiques, biologiques et medicales WO1989007117A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP19880902003 EP0401210A4 (en) 1988-02-01 1988-02-01 Thermally reversible polyurethane hydrogels and cosmetic, biological and medical uses
PCT/US1988/000280 WO1989007117A1 (fr) 1988-02-01 1988-02-01 Hydrogels de polyurethane thermiquement reversibles et leurs applications cosmetiques, biologiques et medicales

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Application Number Priority Date Filing Date Title
PCT/US1988/000280 WO1989007117A1 (fr) 1988-02-01 1988-02-01 Hydrogels de polyurethane thermiquement reversibles et leurs applications cosmetiques, biologiques et medicales

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2235462A (en) * 1989-08-15 1991-03-06 Nat Res Dev Polymeric materials
EP0511570A1 (fr) * 1991-05-01 1992-11-04 Bayer Ag Gels, leur préparation et leur utilisation
GB2260986A (en) * 1991-10-29 1993-05-05 Armstrong World Ind Inc Polyurethane-urea/polyethylene oxide polymers
FR2840907A1 (fr) * 2002-06-14 2003-12-19 Polymerexpert Sa Polymere thermo-sensible ameliore susceptible de former des gels thermoreversibles a haut indice de viscosification
US7033571B2 (en) 2000-06-23 2006-04-25 Battelle Memorial Institute Multiple stimulus reversible hydrogels
US7794657B2 (en) 2003-06-03 2010-09-14 Cantimer, Inc. Phase change sensor
US8460707B2 (en) 2004-08-05 2013-06-11 Ferring B.V. Stabilised prostaglandin composition
US8974813B2 (en) 2006-07-05 2015-03-10 Ferring B.V. Hydrophilic polyurethane compositions
US9987364B2 (en) 2002-09-27 2018-06-05 Ferring B.V. Water-swellable polymers

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US3975350A (en) * 1972-08-02 1976-08-17 Princeton Polymer Laboratories, Incorporated Hydrophilic or hydrogel carrier systems such as coatings, body implants and other articles
US4235980A (en) * 1979-10-19 1980-11-25 E. I. Du Pont De Nemours And Company Elastomeric terionomer blends
US4439585A (en) * 1980-11-12 1984-03-27 Tyndale Plains-Hunter, Ltd. Polyurethane diacrylate compositions as carrier for pharmacological agents
US4496535A (en) * 1980-11-12 1985-01-29 Tyndale Plains-Hunter, Ltd. Polyurethane polyene compositions

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Publication number Priority date Publication date Assignee Title
DE3026575A1 (de) * 1980-07-12 1982-02-04 Bayer Ag, 5090 Leverkusen Antitumoral wirkende mittel
FR2539135B1 (fr) * 1983-01-11 1986-02-28 Essilor Int Hydrogels de polyurethane et procede de fabrication
FR2612194A1 (fr) * 1987-03-27 1988-09-16 Tyndale Plains Hunter Ltd Polyurethane hydrophile et son procede de preparation

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GB2235462A (en) * 1989-08-15 1991-03-06 Nat Res Dev Polymeric materials
GB2235462B (en) * 1989-08-15 1992-12-16 Nat Res Dev Polymeric materials
EP0511570A1 (fr) * 1991-05-01 1992-11-04 Bayer Ag Gels, leur préparation et leur utilisation
US5362834A (en) * 1991-05-01 1994-11-08 Bayer Aktiengesellschaft Gel compounds, their production and use
GB2260986A (en) * 1991-10-29 1993-05-05 Armstrong World Ind Inc Polyurethane-urea/polyethylene oxide polymers
US7033571B2 (en) 2000-06-23 2006-04-25 Battelle Memorial Institute Multiple stimulus reversible hydrogels
FR2840907A1 (fr) * 2002-06-14 2003-12-19 Polymerexpert Sa Polymere thermo-sensible ameliore susceptible de former des gels thermoreversibles a haut indice de viscosification
US9987364B2 (en) 2002-09-27 2018-06-05 Ferring B.V. Water-swellable polymers
US7794657B2 (en) 2003-06-03 2010-09-14 Cantimer, Inc. Phase change sensor
US8460707B2 (en) 2004-08-05 2013-06-11 Ferring B.V. Stabilised prostaglandin composition
US8709482B2 (en) 2004-08-05 2014-04-29 Ferring B.V. Stabilised prostaglandin composition
US8974813B2 (en) 2006-07-05 2015-03-10 Ferring B.V. Hydrophilic polyurethane compositions
US10105445B2 (en) 2006-07-05 2018-10-23 Ferring B.V. Hydrophilic polyurethane compositions

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EP0401210A4 (en) 1990-12-27

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