EP2029107A2 - Utilisation de copolymères acétate de vinyle-sulfonate comme solubilisant pour des composés difficilement solubles dans l'eau - Google Patents

Utilisation de copolymères acétate de vinyle-sulfonate comme solubilisant pour des composés difficilement solubles dans l'eau

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Publication number
EP2029107A2
EP2029107A2 EP07729716A EP07729716A EP2029107A2 EP 2029107 A2 EP2029107 A2 EP 2029107A2 EP 07729716 A EP07729716 A EP 07729716A EP 07729716 A EP07729716 A EP 07729716A EP 2029107 A2 EP2029107 A2 EP 2029107A2
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EP
European Patent Office
Prior art keywords
copolymers
water
soluble
use according
preparations
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Withdrawn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
EP07729716A
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German (de)
English (en)
Inventor
Rainer Dobrawa
Nathalie Bouillo
Ronald Frans Maria Lange
Kathrin MEYER-BÖHM
Murat Mertoglu
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BASF SE
Original Assignee
BASF SE
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Priority to EP07729716A priority Critical patent/EP2029107A2/fr
Publication of EP2029107A2 publication Critical patent/EP2029107A2/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/30—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests characterised by the surfactants
    • 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
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
    • A61K8/8147—Homopolymers or copolymers of acids; Metal or ammonium salts thereof, e.g. crotonic acid, (meth)acrylic acid; Compositions of derivatives of such polymers
    • 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
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
    • A61K8/8152—Homopolymers or copolymers of esters, e.g. (meth)acrylic acid esters; Compositions of derivatives of such polymers
    • 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
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F218/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an acyloxy radical of a saturated carboxylic acid, of carbonic acid or of a haloformic acid
    • C08F218/02—Esters of monocarboxylic acids
    • C08F218/04—Vinyl esters
    • C08F218/08—Vinyl acetate
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
    • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
    • C08F220/10—Esters
    • C08F220/38—Esters containing sulfur
    • C08F220/382—Esters containing sulfur and containing oxygen, e.g. 2-sulfoethyl (meth)acrylate
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F228/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a bond to sulfur or by a heterocyclic ring containing sulfur
    • C08F228/02—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a bond to sulfur or by a heterocyclic ring containing sulfur by a bond to sulfur

Definitions

  • the invention relates to the use of vinyl acetate-sulfonate copolymers as solubilizers of sparingly soluble in water biologically active substances. Furthermore, the invention relates to corresponding preparations for human, animal and plant use and to specific copolymers.
  • Solubilization is understood to mean the solubilization of substances which are soluble or insoluble in a particular solvent, in particular water, by surface-active compounds, the solubilizers. Such solublisers are able to convert poorly water-soluble or water-insoluble substances into clear, at most opalescent aqueous solutions, without the chemical structure of these substances undergoing any change (cf. Römpp Chemie Lexikon, 9th edition, Bd.5. P. 4203, Thieme Verlag, Stuttgart, 1992).
  • solubilizates prepared are characterized in that the poorly water-soluble or water-insoluble substance is colloidally dissolved in the molecular associates of the surface-active compounds which form in aqueous solution-for example the so-called micelles.
  • the resulting solutions are stable single-phase systems that appear optically clear to opalescent and can be prepared without energy input.
  • solubilizers can improve the appearance of cosmetic formulations as well as food preparations by rendering the formulations transparent.
  • the bioavailability and thus the effect of drugs can be increased by the use of solubilizers.
  • solubilizers for pharmaceutical drugs and cosmetic active ingredients surfactants such as ethoxylated (hydrogenated) castor oil, ethoxylated sorbitan fatty acid esters or ethoxylated hydroxystearic acid are mainly used.
  • solubilizers described above, used so far show a number of application disadvantages.
  • the known solubilizers have only a small solubilizing effect for some sparingly soluble drugs such as clotrimazole.
  • solubilizers are usually liquid or semi-solid compounds, which have unfavorable processing properties as a result.
  • Vinyl acetate-sulfonate copolymers are known per se. Corresponding copolymers and their use as textile finishing agents are described, for example, in US Pat. No. 2,834,759.
  • JP-A 51003383 discloses copolymers of vinyl acetate and allylsulfonates and their use as emulsifiers for epoxy resins.
  • Copolymers of vinyl acetate and allylsulfonates and their use as emulsifiers for acrylic resin coating compositions are known from JP-A 50160334.
  • JP-A 09202812 discloses the preparation of polyvinyl esters in the presence of small amounts of allylsulfonates, the allyl sulfonates being known as phase transfer agents.
  • the object was to provide novel solubilizers for pharmaceutical, cosmetic, food-technical as well as agrotechnical applications, which are able to act in aqueous medium as a solubilizer for corresponding sparingly water-soluble active ingredients.
  • the object was achieved by the use of vinyl acetate sulfonate copolymers as solubilizers for sparingly soluble in water substances.
  • Vinyl acetate-sulfonate copolymers according to the invention are copolymers of vinyl acetate and sulfonate-containing monoethylenically unsaturated monomers and optionally further comonomers.
  • Suitable monomers containing sulfonate groups according to the invention are monoethylenically unsaturated sulfonic acid compounds.
  • Suitable sulfonic acid compounds are, for example, sulfonic acid alkyl esters of acrylic acid or methacrylic acid, such as sulfopropyl acrylate or sulfopropyl methacrylate.
  • sulfonic acid-C 1 -C 10 -alkylamides of acrylic acid or of methacrylic acid for example acrylamide-methylpropanesulfonic acid (AMPS).
  • AMPS acrylamide-methylpropanesulfonic acid
  • ⁇ -alkene-1-sulfonic acids having 2 to 10 carbon atoms.
  • Preferred monomers are selected from the group consisting of vinyl sulfonate, allyl sulfonate, methallyl sulfonate (2-methyl-2-propene sulfonate), sulfopropyl acrylate and sulfopropyl methacrylate.
  • the sulfonate monomers are usually used in the form of their salts. Suitable salts are, in particular, the alkali metal salts, for example lithium, potassium or sodium salts, the sodium salts and potassium salts being preferred.
  • the sulfonate monomers are usually fed to the polymerization in the form of aqueous solutions, it being possible for the concentration of the sulfonate monomer to be from 10 to 70% by weight, preferably from 20 to 40% by weight.
  • the sulfonic acid-containing monomers can also be used as solids and dissolved or suspended in the solvent. In the course of the polymerization, the monomer dissolves slowly.
  • the sulfonate group-bearing copolymers are obtainable by copolymerizing a) 80 to 99.5% by weight of vinyl acetate and b) 0.5 to 20% by weight of the sulfonate monomer. Preference is given to using a) 85 to 98% by weight and b) 2 to 15% by weight, particularly preferably a) 85 to 95% by weight and b) 5 to 15% by weight.
  • Suitable solvents are, for example, alcohols, such as methanol, ethanol, n-propanol, and isopropanol, and also glycols, such as ethylene glycol and glycerol. Further suitable solvents are acetic acid esters such as, for example, ethyl acetate or butyl acetate. Preferred solvent is n-propanol.
  • the polymerization is preferably carried out at temperatures of 60 to 100 ° C.
  • the polymerization may be carried out under atmospheric pressure or under an overpressure of up to 1.5 MPa, with atmospheric pressure being preferred.
  • free-radical initiators are used as radical initiators.
  • the amounts of initiator or initiator mixtures used based on the monomer used are between 0.01 and 10 wt .-%, preferably between 0.3 and 5 wt .-%.
  • the polymerization is carried out in such a way that initially an oil-soluble radical initiator, which according to the invention comprises a free-radical initiator which is soluble in organic solvents and insoluble in water, is used. is stood, and at the beginning of the postpolymerization, a water-soluble radical initiator is used.
  • the post-polymerization phase begins in the feed process after the monomer feeds are completely added. In the batch process, the postpolymerization phase is generally considered to account for two-thirds of the total reaction time.
  • Suitable free-radical initiators are both organic and inorganic peroxides such as sodium persulfate or azo initiators such as 2,2'-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride, 2,2'-azobis (2-methylpropionamide) dihydrochloride ), 2,2'-azo bis (2-aminidinopropan) dihydrochloride, 2,2'-azobis (2-methylbutyronitrile), 2,2'-azobis [2- (2-imidazolin-2-yl) propane], 2,2'-azobis (2-methylbutyronitrile), 2,2'-azobisisobutyronitrile, 2,2'-azobis (2,4-dimethylvaleronitrile), dimethyl 2,2'-azobis ( 2-methylpropionate), 2,2'-azobis (4-methoxy-2,4-dimethylvaleronitrile).
  • azo initiators such as 2,2'-azobis [2- (2-imidazolin-2-yl
  • Peroxidic initiators are, for example, dibenzoyl peroxide, diacetyl peroxide, succinic peroxide, tert-butyl perpivalate, tert-butyl 2-ethylhexanoate, tert-butylperneodecanoate, tert-butyl permalate, bis (tert-butylperoxy) cyclohexane, tert.
  • the initiators mentioned can also be used in combination with redox components such as ascorbic acid.
  • Solvent-soluble radical initiators include, for example, 2,2'-azobisisobutyronitrile, 2,2'-azobis (2-methylbutyronitrile), 2,2'-azobis (2,4-dimethylvaleronitrile), dimethyl 2,2'-azobis - (2-methylpropionate), 2,2'-azobis (4-methoxy-2,4-dimethylvaleronitrile), dibenzoyl peroxide, diacetyl peroxide, succinyl peroxide, tert-butyl perpivalate, tert-butyl 2-ethylhexanoate, tert-Butylperneodecanoat, tert Butylpermaleinate, bis (tert-butylperoxy) cyclohexane, tert-butylperoxy-isopropylcarbonate, tert-butylperacetate, 2,2-bis (tert-butylperoxy) -butane, dicumylper
  • the free-radical polymerization can take place in the presence of emulsifiers, if appropriate further protective colloids, if appropriate buffer systems and, if appropriate, subsequent pH adjustment by means of bases or acids.
  • Suitable molecular weight regulators are hydrogen sulfide compounds such as alkyl mercaptans, for example n-dodecyl mercaptan, tert-dodecyl mercaptan, thioglycolic acid and their esters, mercaptoalkanols such as mercaptoethanol. Further suitable regulators are mentioned, for example, in DE 197 12 247 A1, page 4.
  • the required amount of the molecular weight regulator is in the range from 0 to 5% by weight, based on the amount of monomer to be polymerized, in particular 0.05 to 2% by weight, particularly preferably 0.1 to 1.5% by weight.
  • Mercaptoethanol is preferably used.
  • the preparation of the copolymers which can be used according to the invention can also be carried out in the presence of suitable difunctional crosslinker components (crosslinkers) and / or in the presence of suitable regulators.
  • Suitable crosslinkers are those monomers which have a crosslinking function, for example compounds having at least two ethylenically unsaturated, non-conjugated double bonds in the molecule.
  • Examples include acrylic esters, methacrylic esters, allyl ethers or vinyl ethers of at least dihydric alcohols.
  • the OH groups of the underlying alcohols may be completely or partially etherified or esterified; however, the crosslinkers contain at least two ethylenically unsaturated groups.
  • Examples of the underlying alcohols are dihydric alcohols such as 1, 2
  • Ethanediol 1, 2-propanediol, 1, 3-propanediol, 1, 2-butanediol, 1, 3-butanediol, 2,3-butanediol, 1, 4-butanediol, but-2-en-1, 4-diol, 1, 2-pentanediol, 1, 5-pentanediol, 1, 2-hexanediol, 1, 6-hexanediol, 1, 10-decanediol, 1, 2-dodecanediol, 1, 12-dodecanediol, neopentyl glycol, 3-methylpentan-1, 5-diol, 2,5-dimethyl-1,3-hexanediol, 2,2,4-trimethyl-1,3-pentanediol, 1,2-cyclohexanediol, 1,4-cyclohexanediol, 1,4-bis (hydroxymethyl)
  • the ethylene oxide - and Propy contained incorporated lenoxid groups.
  • underlying alcohols having more than two OH groups are trimethylolpropane, glycerol, pentaerythritol, 1, 2,5-pentanetriol, 1, 2,6-hexanetriol, triethoxycyanuric acid, sorbitan, sugars such as sucrose, glucose,
  • the polyhydric alcohols can also be used after reaction with ethylene oxide or propylene oxide as the corresponding ethoxylates or propoxylates.
  • the polyhydric alcohols can also be first converted by reaction with epichlorohydrin in the corresponding glycidyl ether.
  • crosslinkers are the vinyl esters or the esters of monohydric, unsaturated alcohols with ethylenically unsaturated C3 to C6 carboxylic acids, for example Acrylic acid, methacrylic acid, itaconic acid, maleic acid or fumaric acid.
  • examples of such alcohols are allyl alcohol, 1-buten-3-ol, 5-hexen-1-ol, 1-octene-3-ol, 9-decene-1-ol, dicyclopentenyl alcohol, 10-undecen-1-ol, cinnamyl alcohol , Citronellol, crotyl alcohol or cis-9-octadecen-1-ol.
  • esterify the monohydric, unsaturated alcohols with polybasic carboxylic acids for example malonic acid, tartaric acid, trimellitic acid, phthalic acid, terephthalic acid, citric acid or succinic acid.
  • crosslinkers are esters of unsaturated carboxylic acids with the polyhydric alcohols described above, for example oleic acid, crotonic acid, cinnamic acid or 10-undecenoic acid.
  • Suitable crosslinkers are also straight-chain or branched, linear or cyclic, aliphatic or aromatic hydrocarbons which have at least two double bonds which may not be conjugated to aliphatic hydrocarbons, e.g. Divinylbenzene, divinyltoluene, 1, 7-octadiene, 1, 9-decadiene, 4-vinyl-1-cyclohexene, trivinylcyclohexane or polybutadienes having molecular weights from 200 to 20,000.
  • crosslinkers are the acrylic acid amides, methacrylic acid amides and N-allylamines of at least dihydric amines.
  • Such amines are, for example, 1,2-diaminomethane, 1,2-diaminoethane, 1,3-diaminopropane, 1,4-diaminobutane, 1,6-diaminohexane, 1,12-dodecanediamine, piperazine, diethylenetriamine or isophoronediamine.
  • amides of allylamine and unsaturated carboxylic acids such as acrylic acid, methacrylic acid, itaconic acid, maleic acid, or at least divalent carboxylic acids, as described above.
  • triallylamine and triallylmonoalkylammonium salts e.g. Triallylmethylammonium chloride or methylsulfate, suitable as a crosslinker.
  • N-vinyl compounds of urea derivatives at least difunctional amides, cyanurates or urethanes, for example of urea, ethylene urea, propylene urea or tartaramide, e.g. N, N'-divinylethyleneurea or N, N'-divinylpropyleneurea.
  • crosslinkers are divinyldioxane, tetraallylsilane or tetravinylsilane.
  • the monomer or a monomer mixture or the monomer (s) emulsion together with the initiator which is usually in solution, in a stirred reactor at the polymerization temperature presents (batch process), or optionally continuously or in several successive stages in the polymerization reactor metered (feed process).
  • feed process it is customary that the reactor before the actual polymerization in addition to the organic solvent or water (to allow stirring of the reactor) already with subsets, rarely the total amount intended for the polymerization, the starting materials such as emulsifiers, protective colloids , Monomeren, regulators etc. or subsets of the feeds (ia monomer or emulsion feed and initiator feed) is filled.
  • the copolymers thus obtained are water-soluble or water-dispersible.
  • the copolymers may have Fikentscher K values, measured at 1% strength by weight in water, of from 4 to 30, preferably from 5 to 25, particularly preferably from 5 to 15.
  • copolymers to be used according to the invention can in principle be used in all fields in which only sparingly soluble or insoluble substances are to be used in water either in aqueous preparations or should have their effect in an aqueous medium.
  • the copolymers accordingly find use as solubilizers of water-sparingly soluble substances, in particular biologically active substances.
  • the term "sparingly soluble in water” also encompasses practically insoluble substances and means that a solution of the substance in water requires at least 30 to 100 g of water per g of substance at 20 ° C. In the case of practically insoluble substances, at least 10,000 g of water per g substance needed.
  • water-sparingly soluble biologically active substances are pharmaceutical active substances for humans and animals, cosmetic or agrochemical active substances or dietary supplements or dietary active substances.
  • Also suitable as the sparingly soluble substances to be solubilized are also dyes such as inorganic or organic pigments.
  • amphiphilic compounds for use as solubilizers for pharmaceutical and cosmetic preparations and food preparations are provided. They have the property of poorly soluble active ingredients in the field of pharmacy and cosmetics, sparingly soluble supplements, for example, vitamins and carotenoids but also to solubilize sparingly soluble active ingredients for use in plant protection products and veterinary active ingredients.
  • the copolymers can be used as solubilizers in cosmetic formulations.
  • they are suitable as solubilizers for cosmetic oils. They have good solubility for fats and oils such as peanut oil, jojoba oil, coconut oil, almond oil, olive oil, palm oil, castor oil, soybean oil or wheat germ oil or for essential oils such as mountain pine oil, lavender oil, rosemary oil, pine needle oil, pine needle oil, eucalyptus oil, peppermint oil, sage oil, bergamot oil , Turpentine oil, lemon balm oil, juniper oil, lemon oil, aniseed oil, cardamom oil; Camphor oil etc. or for mixtures of these oils.
  • fats and oils such as peanut oil, jojoba oil, coconut oil, almond oil, olive oil, palm oil, castor oil, soybean oil or wheat germ oil or for essential oils such as mountain pine oil, lavender oil, rosemary oil, pine needle oil, pine needle oil, eucalyptus oil, peppermint oil, sage oil,
  • the polymers according to the invention can be used as solubilizers for water-insoluble or insoluble UV absorbers such as, for example, 2-hydroxy-4-methoxybenzophenone (Uvinul® M 40, BASF), 2,2 ', 4,4'-tetrahydroxybenzophenone (Uvinul® D 50), 2,2'-dihydroxy-4,4'-dimethoxybenzophenone (Uvinul® D49), 2,4-dihydroxybenzophenone (Uvinul® 400), 2-cyano-3,3-diphenylacrylic acid 2'-ethylhexyl ester (Uvinul ® N 539), 2,4,6-trianilino-p- (carbo-2'-ethylhexyl-1 '-oxi) -1, 3,5-triazine (Uvinul ® T 150), 3- (4-methoxybenzylidene) -camphor (Eusolex ® 6300, Fa.
  • water-insoluble or insoluble UV absorbers such
  • the present invention therefore also cosmetic preparations containing at least one of the copolymers of the invention mentioned above as solubilizers. Preference is given to those preparations which, in addition to the solubilizer, contain one or more sparingly soluble cosmetic active ingredients, for example the abovementioned oils or UV absorbers.
  • formulations are water or water / alcohol based solubilisates.
  • the solubilizers according to the invention are used in a ratio of 0.2: 1 to 20: 1, preferably 1: 1 to 15: 1, more preferably 2: 1 to 12: 1 to the sparingly soluble cosmetic active ingredient.
  • the content of solubilizer according to the invention in the cosmetic preparation is, depending on the active ingredient, in the range of 1 to 50 wt .-%, preferably 3 to 40 wt .-%, particularly preferably 5 to 30 wt .-%.
  • auxiliaries may be added to this formulation, for example nonionic, cationic or anionic surfactants such as alkylpolyglycosides, fatty alcohol sulfates, fatty alcohol ether sulfates, alkanesulfonates, fatty alcohol ethoxylates, fatty alcohol phosphates, alkylbetaines, sorbitan esters, POE sorbitan esters, sugar fatty acid esters, fatty acid polyglycerol esters, fatty acid partial glycerides, fatty acid carboxylates, fatty alcohol sulfosuccinates, fatty acid sarcosinates , Fatty acid isethionates, fatty acid taurinates, citric acid esters, silicone copolymers, fatty acid polyglycol esters, fatty acid amides, fatty acid alkanolamides, quaternary ammonium compounds, alkylphenol oxethylates, fatty oxe
  • natural or synthetic compounds e.g. Lanolin derivatives, cholesterol derivatives, isopropyl myristate, isopropyl palmitate, electrolytes, dyes, preservatives, acids (e.g., lactic acid, citric acid).
  • formulations are used, for example, in bath-supplement preparations such as bath oils, shaving waters, face lotions, hair lotions, colognes, toilet water and in sunscreens.
  • bath-supplement preparations such as bath oils, shaving waters, face lotions, hair lotions, colognes, toilet water and in sunscreens.
  • Another field of application is the field of oral care, for example in mouthwashes, toothpastes, denture detersive creams and the like.
  • copolymers are also suitable for industrial applications, for example for preparations of sparingly soluble colorants, in toners, preparations of magnetic pigments and the like.
  • the copolymers according to the invention can be used as a 100% substance or preferably as an aqueous solution.
  • the solubilizer is usually dissolved in water and intensively mixed with the sparingly soluble cosmetic active ingredient to be used in each case.
  • solubilizer it is also possible for the solubilizer to be intensively mixed with the sparingly soluble cosmetic active ingredient to be used in each case and then mixed with demineralized water with constant stirring.
  • Solubilizers for pharmaceutical applications are also suitable for use as solubilizers in pharmaceutical preparations of any kind, which are characterized in that they may contain one or more sparingly soluble in water or insoluble in water drugs and vitamins and / or carotenoids. In particular, these are aqueous solutions or solubilisates for oral administration.
  • the claimed copolymers are suitable for use in oral dosage forms such as tablets, capsules, powders, solutions.
  • oral dosage forms such as tablets, capsules, powders, solutions.
  • solid solutions of active ingredient and solubilizer find use.
  • emulsions for example fat emulsions
  • the claimed copolymers are suitable for processing a sparingly soluble drug.
  • compositions of the above type may be obtained by processing the claimed copolymers with pharmaceutically active agents by conventional methods and using known and novel drugs.
  • the application according to the invention may additionally contain pharmaceutical excipients and / or diluents.
  • adjuvants cosolvents, stabilizers, preservatives are particularly listed.
  • the pharmaceutical active ingredients used are water-insoluble or sparingly soluble substances. According to DAB 9 (German Pharmacopoeia), the solubility of pharmaceutical active ingredients is classified as follows: sparingly soluble (soluble in 30 to 100 parts of solvent); poorly soluble (soluble in 100 to 1000 parts of solvent); practically insoluble (soluble in more than 10,000 parts solvent).
  • the active ingredients can come from any indication.
  • Examples include benzodiazepines, antihypertensives, vitamins, cytostatics - especially taxol, anesthetics, neuroleptics, antidepressants, antibiotics, antimycotics, fungicides, chemotherapeutics, urologics, antiplatelet agents, sulfa drugs, spasmolytics, hormones, immunoglobulins, sera, thyroid drugs, psychotropic drugs, Parkinson's and others Anti-hyperkinetics, ophthalmics, neuropathic preparations, calcium metabolism regulators, muscle relaxants, anesthetics,
  • Lipid-lowering agents liver therapeutics, coronary agents, cardiac drugs, immunotherapeutics, regulatory peptides and their inhibitors, hypnotics, sedatives, gynecologics, gout, fibrinolytics, enzyme preparations and transport proteins, enzyme inhibitors, emetics, circulation-enhancing agents, diuretics, diagnostics, corticoids, cholinergics, gallium pathogens, antiasthmatics , Broncholytics, beta-blockers, calcium antagonists, ACE inhibitors, atherosclerosis agents, antiphlogistics, anticoagulants, antihypotonics, antihypoglycemics, antihypertensives, antifibrinolytics, anticonvulsants, Antiemetics, antidotes, antidiabetics, antiarrhythmics, antianemics, antiallergic drugs, anthelmintics, analgesics, analeptics, aldosterone antagonists, emaciation agents.
  • a possible preparation variant is the dissolution of the solubilizer in the aqueous phase, optionally with gentle heating and the subsequent dissolution of the active ingredient in the aqueous solubilizer solution.
  • the simultaneous dissolution of solubilizer and active ingredient in the aqueous phase is also possible.
  • copolymers according to the invention as a solubilizer can also be carried out, for example, by dispersing the active ingredient in the solubilizer, if appropriate with heating, and mixing it with water while stirring.
  • solubilizers can also be processed in the melt with the active ingredients.
  • solid solutions can be obtained in this way.
  • the method of melt extrusion is suitable for this purpose.
  • Another possibility for the preparation of solid solutions is also to prepare solutions of solubilizer and active ingredient in suitable organic solvents and then to remove the solvent by conventional methods.
  • injection molding processes and melt granulation processes are also suitable for the production of solid solutions.
  • the invention therefore also relates generally to pharmaceutical preparations which contain at least one of the copolymers according to the invention as a solubilizer. Preference is given to those preparations which, in addition to the solubilizer, contain a sparingly soluble or water-insoluble pharmaceutical active substance, for example from the above-mentioned indications.
  • Particularly preferred of the abovementioned pharmaceutical preparations are those which are orally administrable formulations.
  • the content of solubilizer according to the invention in the pharmaceutical preparation is, depending on the active ingredient, in the range of 1 to 75 wt .-%, preferably 5 to 60 wt .-%, particularly preferably 5 to 50 wt .-%.
  • Another particularly preferred embodiment relates to pharmaceutical preparations in which the active ingredients and the solubilizer are present as a solid solution.
  • the weight ratio of solubilizer to active ingredient is preferably from 1: 1 to 4: 1.
  • copolymers according to the invention are also suitable as solubilizers in the food industry for nutrients, auxiliaries or additives which are sparingly soluble in water or which are insoluble in water, for example.
  • fat-soluble vitamins or carotenoids examples include clear, colored with carotenoids drinks.
  • compositions include pesticides, herbicides, fungicides or insecticides, especially those preparations of pesticides used as spray or pouring broths.
  • the sulfonate copolymers used according to the invention are distinguished by a particularly good solubilizing effect.
  • Feed 1 156.9 g of sodium vinyl sulfonate (25% strength by weight in water)
  • Feed 2 1.2 g of tert-butylperneodecanoate, 50 g of methanol
  • the preparation was carried out in a 2 liter stirred tank under a nitrogen atmosphere.
  • the original was heated to 65 ° C at a stirrer speed of 100 rpm.
  • feed 1 was added over a period of 2 hours and feed 2 over a period of 3 hours.
  • it was postpolymerized for 2 hours.
  • the organic solvent was removed by steam distillation and a cloudy aqueous solution having a solids content of 25.4 wt .-% was obtained.
  • the K value of the polymer was 25.5 (1 wt% in water).
  • the preparation was carried out analogously to Example 2. After the steam distillation, the polymer was isolated by freeze-drying. The K value was 7.6 (1% strength by weight in water).
  • Feed 1 250 g of methanol, 20 g of potassium sulfopropyl methacrylate (25% strength by weight in water)
  • Feed 2 1.5 g of tert-butylperneodecanoate, 50 g of methanol
  • Feed 3 1.5 g of tert-butyl perneodecanoate
  • the preparation was carried out in a 2 liter stirred tank under a nitrogen atmosphere.
  • the original was heated to 64 ° C internal temperature at a stirrer speed of 100 rpm. Then Feed 1 was added over a period of 4 hours and Feed 2 over a period of 5 hours. Subsequently, feed 3 was added for 2 hours at 64 ° C postpolymerized. Thereafter, the organic solvent was removed by means of steam distillation and a white turbid aqueous solution having a solids content of 27.8 wt .-% was obtained.
  • Feed 1 114, 3 g of sodium allylsulfonate (35% by weight in water)
  • Feed 4 4.00 g of 2,2'-azobis (2-amidinopropane) dihydrochloride
  • Example 6 The preparation of Example 6 was carried out analogously to Example 5, except that the sodium allylsulfonate solution used was not neutralized with sulfuric acid.
  • the resulting aqueous solution has a solids content of 22.1%, the K value of the polymer was 9.1 (1 wt .-% in water).
  • Each batch of drug is given as follows to obtain a supersaturated solution. (If the weighed mass dissolved in the medium, the weight was increased until the formation of a sediment).
  • phosphate buffer pH 7.0 was added until solubilizer and phosphate buffer in the weight ratio of 1:10 were present. With the aid of a magnetic stirrer, this mixture was stirred at 20 ° C for 72 hours. Then at least a 1 hour rest period. After filtration of the batch, this was measured photometrically and determines the content of active ingredient.
  • Piroxicam Copolymer according to Example no. / Solubilization at 20 ° C. in [g / 100 ml]
  • the active ingredient and the polymer were weighed into a suitable glass vessel in a weight ratio of 1: 1 (in each case 2 g) and then 16 ml of dimethylformamide were added as solvent.
  • the batch was stirred at 20 ° C for 24 hours on a magnetic stirrer.
  • the solution was then pulled out on a glass plate with the aid of a 120 ⁇ m doctor blade. This was dried for 0.5 hours at RT in a fume hood and then dried in a drying oven at 50 ° C. and 10 mbar for a further 0.5 hours in order to remove the solvent quantitatively.
  • the samples were then visually inspected.

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Abstract

Utilisation de copolymères, obtenus par copolymérisation initiée de manière radicalaire de a) 80 à 99,5 % en poids d'acétate de vinyle et b) 0,5 à 20 % en poids d'un monomère monooléfiniquement insaturé portant un groupe sulfonate, comme solubilisant pour des substances difficilement solubles dans l'eau.
EP07729716A 2006-06-07 2007-05-31 Utilisation de copolymères acétate de vinyle-sulfonate comme solubilisant pour des composés difficilement solubles dans l'eau Withdrawn EP2029107A2 (fr)

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EP07729716A EP2029107A2 (fr) 2006-06-07 2007-05-31 Utilisation de copolymères acétate de vinyle-sulfonate comme solubilisant pour des composés difficilement solubles dans l'eau

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EP06115089 2006-06-07
PCT/EP2007/055309 WO2007141182A2 (fr) 2006-06-07 2007-05-31 Utilisation de copolymères acétate de vinyle-sulfonate comme solubilisant pour des composés difficilement solubles dans l'eau
EP07729716A EP2029107A2 (fr) 2006-06-07 2007-05-31 Utilisation de copolymères acétate de vinyle-sulfonate comme solubilisant pour des composés difficilement solubles dans l'eau

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US8025899B2 (en) 2003-08-28 2011-09-27 Abbott Laboratories Solid pharmaceutical dosage form
MX2009013810A (es) * 2007-07-06 2010-01-27 Basf Se Uso de homo y copolimeros para la estabilizacion de formulaciones de principios activos.
AU2008334580A1 (en) * 2007-12-12 2009-06-18 Basf Se Salts of active ingredients with polymeric counter-ions
US20090163449A1 (en) * 2007-12-20 2009-06-25 Eastman Chemical Company Sulfo-polymer powder and sulfo-polymer powder blends with carriers and/or additives
CN103158206A (zh) * 2013-03-19 2013-06-19 太仓市佳玲塑料制品有限公司 一种醋酸乙烯造粒的制备工艺
US11254620B2 (en) * 2013-08-05 2022-02-22 Verdesian Life Sciences U.S., Llc Micronutrient-enhanced polymeric seed coatings
GB201405624D0 (en) 2014-03-28 2014-05-14 Synthomer Uk Ltd Method of making a branched polymer, a branched polymer and uses of such a polymer
US10647793B2 (en) 2014-03-28 2020-05-12 Synthomer (Uk) Limited Use of a sulphur or phosphorous-containing polymer as a processing aid in a polyvinyl chloride polymer composition
CN106133009B (zh) 2014-03-28 2019-04-30 辛色姆（英国）有限公司 用于悬浮聚合反应的二级悬浮剂
WO2017032651A1 (fr) 2015-08-21 2017-03-02 Basf Se Sels de principes actifs ayant des contre-ions polymères
AU2016317605B2 (en) * 2015-09-04 2021-01-07 Sumitomo Chemical Company, Limited Composition, method for producing composition, and pesticide composition
CN107793520B (zh) * 2016-09-07 2020-10-23 中国石油化工股份有限公司 一种制备聚乙烯-聚乙酸乙烯酯弹性体无皂微乳液的方法
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