MXPA96005422A - Polymeric mixtures containing absorbib polioxaesters - Google Patents

Abstract

The present invention discloses novel aliphatic polyoxaesters and mixtures thereof which can be used to produce surgical devices such as sutures, sutures with attached needles, molded devices, and the like, the invention also contemplates a process for the production of these polyesters, the polyoxaesters aliphatics of the present invention have a first divalent repeat unit of formula I: [OC (O) -C (R1) (R2) -O- (R3) -OC (R1) (R2) -C (O) -] (i), and a second repeat unit selected from the group of formulas consisting of: [- O-R4-] A (ii); [- O-R5-C (O) -] B (iii); [-O-R5-C (O)] PO-) LG (XI), and combinations thereof, these aliphatic polyoxaesters may be mixed with other polymers which are preferably biocompatible.

Description

POLYMERIC MIXTURES CONTAINING ABSORBABLE POLIOXAESTERS FIELD OF THE INVENTION The present invention is a continuation in part of the serial number 08 / 554,011, filed on November 6, 1955, which is a continuation in delivery of the serial number 08 / 399,308, presented the end of 1995 and 1995, now pa + en No. 5,454,929 (and all of which are incorporated herein by reference), The present invention relates to a bioresorbable polymeric material and mixtures thereof and more particularly to absorbable surgical products made from polymers and mixtures thereof. the same.

BACKGROUND OF THE INVENTION From the first Carothers job in the 20s and 30s, aromatic polyesters, often polyethylene terephthalate, have become the most important polyesters commercially. The utility of polymers is intimately linked to the hardening action of the p-femlene group in the polymer chain. The presence of the ptenol group in the base structure of the polymer chain leads to high melting points and good mechanical properties especially for fibers, films and some molded products. In fact, polyethylene terephthalate has become the polymer of choice for many common consumer products, such as one and two liter soda containers. Different related polyester resins have been described in U.S. Patents 4,440,922, 4,552,948 and 4,963,541 which seek to improve the properties of terephthalate or polyethylene by replacing the erephthalic acid with other related dicarboxylated acids containing phenylene groups. These polymers are generally designed to reduce the gas permeability of aromatic polyesters. Other aromatic polyesters have also been developed for special applications such as stable bioabsorbable radiation materials. U.S. Patent Nos. 4,510,295, 4,545,152 and 1,689,424 describe stable aromatic radiation polyesters that can be used to make sutures and the like. These polymers, such as polyethylene terephthalate, have groups of tena wood in the base structure of the polymers. However, less research has been reported on polyesters to fatics. After the first work of Carot-her about polyesters, the polastosteres to the faticos were generally ignored because it was believed that these materials had low melting points and high solubilities. The only polyphenols that have been extensively studied are polylactones such as polylactide, polyglycol, poly (μ-ioxanone) and poly caprolactone. These aliphatic pol lactones have been used mainly for bioresorbable surgical sutures and surgical devices such as staples, Although the polylactones have proven to be useful in many applications, they do not cover all the needs of the medical community. For example, Pol lactone films do not readily transmit water vapor, therefore, they are not ideally suited for use as bandages where the transmission of water vapor would be desirable. Only recently has interest in polyesters alifata eos without lactone been renewed. U.S. Patent 5,349,028 describes the formation of very simple aliphatic polyesters based on the reaction of a diol with a dicarboxylic acid to form prepolymer chains which are then coupled. These polyesters have been promoted for use in fibers and molded articles since these polyesters are L > They are degradable after they are treated as in a field. However, these devices are not described as suitable for use in surgical devices. Thus it is an object of the present invention to provide a new class of aliphatic polyesters and mixtures thereof which are bioabsorbable and can be used in surgical devices such as sutures, molded devices, drug delivery matrices, coatings, lubricants and Similar.

BRIEF DESCRIPTION OF THE INVENTION A new class of synthetic polymeric materials and mixtures thereof have been discovered that can be used to produce surgical devices such as sutures, sutures with added needles, molded devices, drug delivery matrices, coatings, lubricants and the like. The invention also contemplates a process for the production of bioabsorbable polymers and copolymers. The polymer blends of the present invention comprise aliphatic polyoxa esters having a first divalent repeat unit of formula I: C0-C (0) -C (R?) (R2) -O-ÍR3? -O-C (R?) (R2) ~ C (0) -] I and a second repeating unit selected from the group of formulas consisting of: C-0-R «-] A, II G.-O-RS-C (O) -] B, nor ([-0-Rs- C (0)] p ~ 0-) LG XI and combinations thereof, wherein Ri and R2 are independently hydrogen or an alkyl group containing from 1 to 8 carbon atoms; R3 is an alkylene unit containing from 2 to 12 carbon atoms or is an oxyalkylene group of the following formula: ~ C (CH2) C-0-1D- (CH2) E-IV where C is an integer on the scale of 2 to about 5, D is an integer on the scale of about 0 to about 2,000, and E is an integer on the scale of about 2 to about 5, except when D is zero, in which case E will be an integer from 0 to 12; R is an alkylene unit containing from 2 to 8 carbon atoms: D is an integer in the scale from 1 to 2000; R5 is selected from the group consisting of ~ C (R6) (R7) -, - (CH2) 3-0-, -CH2-CH2-O-CH2--, -CR8H-OH2-, - < CH2) «-, - (CH2) F-0-C (0) - and (CH2) F -C (0) ~ CH2-; Re and R7 are independently hydrogen or an alkyl containing from 1 to 8 carbon atoms; Re is hydrogen or methyl; F is an integer on the scale of 2 to 6; B is an integer on the scale of 1 to n so that the number-average molecular weight of formula III is less than about 200,000, preferably less than about 100,000, and most preferably less than 40,000; P is an integer on the scale of 1 to m of + to the form that the number-average molecular weight of formula XI is less than about 1,000,000, preferably less than about 200,000 and most preferably less than 40,000; G represents the residue of at least 1 to L atoms of hydrogen of the hadroxyl group of an alcohol previously containing from 1 to 200 hadroxyl groups to roxamadam nte; and I. is an integer from 1 to 200 approximately; and a second polymer selected from the group consisting of lactone-type polymer homopolymer and copolymer with the repeating units described with formulas III and XI, aliphatic polyurethanes, polyether polyurethanes, polyester polyurethanes, polyethylene copolymers, polyamides, polyvinyl alcohols, poly (ethylene oxide), polypropylene oxide, polyethylene glycol, polypropylene glycol, polytetranethylene oxide, polyvinyl.Ipyrrolidone, polyacrylamide, poly (hydroxyethylacrylate), poly (hydroxyethyl ethacrylate) and combinations thereof ..

DETAILED DESCRIPTION OF THE INVENTION The aliphatic? Oxamples of the present invention are the reaction product of an aliphatic polyoxycarboxylic acid and at least one of the following compounds: a diol (or polydiol), a lactone (or oligome or lactone), a coupling agent or combination thereof. Suitable alpha-oxycarboxylic acids suitable for use in the present invention generally have the following formula: H0-C (0) -C (R?) (R2) -0- (R3) -0-C (R?) (R2) -C (0) -0H V wherein Ri and R2 are independently selected from the group consisting of hydrogen or an alkyl group containing from 1 to 8 carbon atoms and R3 is an alkylene containing from 2 to 12 carbon atoms or is an oxyalkylene group of the following formula: -C (CH2) C-0-1D-ÍCH2) E- IV where C is an integer on the scale of about 2 to about 5, D is an integer on the scale of about 0 to about 2, 000 and preferably from 0 to 12, and E is an integer on the scale of about 2 to about 5. These aliphatic alpha-hydroxycarboxylic acids can be formed by reacting a diol or polydiol with an alpha-halocarboxylic acid such as brornoacetic acid or chloroacetic acid under suitable conditions. Suitable diols or polyidioles for use in the present invention are diols or diol repeating units with up to 8 carbon atoms having the formulas: HC- (0-R «-) A30H VI wherein R 4 is an alkylene unit containing from 2 to 8 methylene units; A is an integer in the range of 1 to about 2,000 and preferably of about 1000. Examples of suitable diols include diols selected from the group consisting of 1, 2, ethanediol (ethylene glycol), 1,2-propanediol (propylene glycol), 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol, 1,3-cyclopentanediol, 1,6-hexanediol, 1,4-cyclohexanediol, 1,8-octanediol and combinations thereof. Examples of preferred polycides include polycides selected from the group consisting of polyethylene glycol (HC-0-CH2-CH2-3AOH) and polypropylene glycol (HC-O-CH2-CH- (CH3) -AOH). The polymer produced by reacting the aliphatic dioxycarboxylic acid with the diols described above should provide a polymer that generally has the formula: C-0-C (0) -C (I) (R) -0- (R3) -O-C (RI) (R2) ~ C (0) - (O-R4) A ~ JN VII wherein Ri, R2, R3 «and A are as described above; and N is an integer on the scale of about 1 to about ,000 and preferably is in the range of about 10 to about 1,000 and most preferred in the range of 50 to about 200. Suitable lactone monomers that can be used in the present invention generally have the formula: rO-Rs-C (0) p, VIII These lactone monomers can be polymerized to provide polymers of the following general structures: HC-0-RS-C (0) -] BOH IX (H [-0 ~ RS-C (0)] p -0-) LG X wherein Rs is selected from the group consisting of C RßHR?) -, - (CH2) 3 ~ 0-, -CH2-CH2-O-CH2-, -CRßH-CH2 ~, - (CH2 ~, - (CH2) F-0-C (0) -, and - (CH 2) F -C (0) -CH 2 -; Re and R 1 are independently hydrogen or an alkyl group containing from 1 to 8 carbon atoms; Re is hydrogen or methyl, F is an integer from about 2 to 5, B is an integer in the scale of 1 an in such a way that the number average molecular weight of formula IX is less than about 200,000, preferably less than 100,000, and most preferably less than 40,000; P is an integer in the 1 am scale such that the number average molecular weight of formula X is less than about 1,000,000, preferably less than 200,000, and most preferably less than 40,000; G represents the residue minus 1 to L hydrogen atoms of the hydroxyl groups of an alcohol previously containing from 1 to 200 hydroxyl groups, and L is an integer from about 1 to 200. In a G mode it is the residue of a dihydroxy alcohol minus both hydroxyl groups. In another embodiment of the present invention, G may be a polymer containing pendant hydroxyl groups (including polysaccharides). Suitable repeating units derived from lactone can be generated from the following monomers including but not limited to lactone monomers selected from the group consisting of glycolide, d-lactide, 1-lactide, eso-lactide, S-caprolactone, p-dioxanone, tri ethylene carbonate, 1,4-dioxe? an-2 -one, 1,5-dioxepan-2-one, and combinations thereof. The polymer formed by reacting the above-described diol (or polydiol) VI and the aliphatic polyoxycarboxylic acid V, can also be copolymerized in a condensation polymerization with the lactone IX polymers described above to form a polymer generally of the formula: [(-C (O) -C (R?) (R2) ~ 0 -R3-0-C (R?) (R2) -C (0) - (0 -R «) A ~ 0) S (C (0) -RS-0) B3W XII or [(-C (O) -C (R?) (R2) ~ 0 ~ R3-0-C (R?) (R2) -C (0) - (0) -R «) A -0) S (C-0-R5 ~ C) 0) J > -0 ~) | _G] W XIII wherein S is an integer on the scale of about 1 to 10,000 and preferably about 1 to 1,000 and U is an integer on the scale of about 1 to about 1,000. These polymers can be made in the form of random copolymers or block copolymers. For the diols, the aliphatic polyoxycarboxylic acids and lactone monomers described above may be added a coupling agent-selected from the group consisting of tri-functional or tetrafunctional polyols, oxycarboxylic acids, and polybasic carboxylic acids (or acid anhydrides thereof). The addition of 1 l The n-coupler causes the branching of long chains, which can impart desirable properties in the molten state to the μoLiester prepolder. Examples of suitable pol a-functional coupling agents include tprnet lol-lropane, l, glycerin, pent a ntol, rnal acid, citric acid, tart rich acid, trunic acid, acid prop no-t ricarbox L co, < ? nh? drado ci clopent ano acarbox il co and combinations of lni nni .. The amount of coupling agent to be added before the gelation is a function of the type of coupling agent used and the polymerization conditions of the loxaest or molecular weight of the Limero prepo to which it is added .. Gene lmen on the scale of approximately Ol to about LO molos porcaento of a copied agent, 1 functional or functional tp can be added based on mole1; pol u u u u u pol pol pol fut fut fut fut fut fut pol pol pol pol pol pol pol Behind the synthesis, the polioxester of the polyoxaester is preferably used to conduct polymer condensation eonutes. fused in pr-essence of an organometallic catalyst at elevated temperatures. The organometallic catalyst is preferably a tin catalyst, for example, a stannous oxide. The catalyst will preferably be present in the mixture in a molar ratio of acid! . > '- μoLiox carbox i The aliphatic and optional lactone-to-catalyst men- toon' - was on the scale of alr-eder- from 15.00!) to approximately 80,000 / 1., The reaction is preferably carried out at a temperature not less than about 1 0T under reduced pressure, higher polymerization temperatures may lead to further increases in the molecular weight of the copolymer, which may be desirable for numerous applications. The exact reaction conditions chosen will depend on numerous factors, including the properties of the desired polymer, the viscose «Jad of the reaction mixture, and the glass transition temperature and polymer softening temperature. The preferred reaction conditions of temperature, time and pressure can be determined to ensure these and other factors. Generally, the reaction mixture is maintained at approximately 2 ° C. The polymerization reaction can Allow this temperature to proceed until the desired molecular weight and percentage conversion is achieved by the copolymer, which will take from about 15 minutes to 24 hours. Rl increase- the reaction temperature generally decreases the reaction time required to achieve a weight molecular partí cu Lar. In another embodiment, the copolymers < The aliphatic polyoxester can be prepared by forming an aliphatic polyoxy ester prepolymer, which is polymerized under the conditions of a polymeric condensation, two phases, or at least one ' > > - monomero de lactona or μrepol uero de lactona. The mixture should then be subjected to the desired temperature conditions and the time to couple the prepolymer? with the lac ona rnoriomeros. 1: 1 Molecular weight of the prepolymer as well as its composite can be varied "Jependando of the desired characteristic 5 that the prepoliner will impart < ? 1 copter uñero. However, it is preferred that the polyolefin wing tips of which the lime flake is prepared have a molecular weight that provides an inherent viscosity of from about 0.02 to about 0.25 deciliters per gram.

LO (dl / g) as used in a solution of hexafluoroisopropane J from 0.1 g / dl to 25c, 0"Those of ordinary skill in the art will appreciate that the reagents of the polyoxaesther ultrasols described in US Pat. the present can also be made or split from mixtures of more than one diol and di-ox acid LcarL > ox? l ico. L5 One of the beneficial properties of pol loxuester al a f? The fact of the procedure is that it is annealed, that the ester bonds are unstable, and therefore the polymer is babbased because it is livid in small segments when exposed. on the roof, the body of the body. 0 In this regard, it should be noted that the eo-roactives can be incorporated into the leachate mixture of ioxycarboxylic acid and aliphatic acid and the diol for the formation of the aliphatic poloxaester lunar moiety. It is preferable that the reaction mixture does not anchor a concentration of 1! Co-mater iai reacoionable that the prepared non-absorbable polymer can give. Pre f ora blemen e, the leaction mixture is l? Substantially free from any club < only if the resulting polymer is not absorbable. These aliphatic polxaesters described herein and those described in the number of senes 08 / 399,308, l > filed on March 6, 1995 and assigned to Ethicon, now US Patent No. 5,464,929 can be mixed with other copolymers, copolymers and graft copolymers to impart new properties to the material formed by the blend. pol loxaesters aliphatic can The mixtures include, but are not limited to, polypropylene or polyethylene, polyurethane, polyurethane, polyurethane, polyurethane, polyurethane, polyurethane. polaester, flake! full polyethylene umbrellas (such co or co-owners) Lr? of ot acetate Len-vina lo and copoluneros do acp lato do ti len-et a 1 o), pol aamida, pol a va va 1 i eo alcohols, full polymer oxide, polypropylene oxide, polyethylene 1 i co 1 polapropí lengl icol, oxide of pol i tet ramet i leño, pol a vi ni 1 pi r rol idona, poliacra larní da, ucplato de M) pol to hydrox et i Lo, met acp lato de pol i hi drox? Et i lo. The copellers (that is to say, with two or more repeat units) include several copoLunees in blocks and segments. Suitable repeating units derived from lactone can be generated from the following? I? Onomer-os that J include but are not limited to selected Lactone onomeros from the group consisting of laccol, d-laotide, 1-lac? Da, mesolact, capr olotone, p-dioxanone. , carbonate «le tr ~ a rnet i lene, l, 4 ~ d? oxepanone, 1, 5-d? oxe? a-2 ona and combinations of the same. The mixtures may contain about 1% by weight to about 99% by weight of the polyesters to the licit. For some applications it may be desirable to add i ngredaent e < -, added them such as stabilizers, radiopaque, ant? x i before, fillings or similar, The polymer mixtures of this invention may be 1) f) be set up by "" "" "" "" "" "'' '' '' '' '' '' 'methods to prepare a wide range of utale devices. These polymer blends can be injection molded or compression molded to make medical surgical facilities especially ablative, devices for ripping wounds. The devices ?? e f was two LL5 to close- wounds are secure, staples and surgical sutures. Alternatively, the polymer mixtures can be oxidized to prepare fibers. The thus produced Laments can be manufactured in sutures or ridges, pledged to surgical needles, packaged, and sterilized by means of known techniques. The polymers of the present invention can be woven. 11 f 11 ament and weaving or spinning to form sponges or gauzes, (or non-woven savannahs that are designed for use) or used together with other (compression structures as a device--, prosthetic The structure of the body of a human or animal where it is desirable that the structure is designed with desirable levels of docility and / or ductility, useful styles include tubes, which include branched hubs. , for artery, vein, or intestinal repair, nerve joint, tendon joint, sheets to check and • Support damaged surface abrasions, particularly 5 major abrasions, or areas where the skin and underlying tissues are damaged or surgically removed., the polymer blends can be molded to (pee) films which, when sterilized, are useful as adhesion prevention barriers.Other technique The pro-choice alternative for the polymer blends of this invention includes solvento molding, par ti cuiai mont e for those applications where a drug release flask is desired With the detail, Surgical and medical uses of the filaments, pellets, and molded articles of the present invention include, but do not need to be limited as well. Spun products, non-woven fabrics, and molded products, which include: a) bandage for burns 20 b) patches for hernia c "medical bandages" I. facial substitutes and gauzes, cloth, savanna, felt or sponge for he ot asa s of hi ao, >; ', (.. bandages of «jasa g. graft uit era al or substitutes Li. bandages for skin surfaces a, suture knot fastener j, pins, fasteners, turn messes and plates ot opedi cas b I- - safe (for example, for vena cava) L "staples" n "hooks, buttons, and fasteners n. substi tts of bones (for example, prosthesis of rna nula) 0 or .. intrauterine devices (e. Specifics) tubes for drainage or test or capillaries surgical instruments r implants or vascular supports 5 s disks see ebrales t tube ex t raoor poreo for machines of heart and pneumonia - lung skin and fi l catheters (including, but not limited to, the catheters described in North American Patent No. 4, (183,099 which is incorporated herein by reference)? frames for upl i caci Tone engineering, fn ot modality, the attic pneumatic generator can be used? go a surface of a urtjouLo M > surgical? ar < - \ improve the lubricity of the < -uperíae? e coated. The polymer can be applied as a coating lue ut Liza conventional techniques. For example, the polyester can be placed in a diluted solution of a volatile organic solvent by (eg, acetone, methanol, ethyl acetate or toluene, and then the polymer can be immersed in the solution to coat its surface. Once the surface is coated, the surgical article can be removed from the solution where it can be dried at ambient or elevated temperatures, until the oliver is removed and any muting is removed. .. 0 used in coating applications or polymer blends must exhibit an inherent viscosity, as measured in 0.1 gram per deciliter (g / dl) of hexa fl uoroi sopropanol 0-IF1P), between about 0.5 to about 2.0 dl / g, preferably from about 0.10 5 to about 0"80 dL / g" If the inherent viscosity was lower than 0.05 dl / g, then the polymer mixtures can not have the necessary integrity for the preparation. «Je movies or re coverings for the assumptions of various surgical and medical articles. On the other hand, although it is possible to use polymer blends with a higher inherent viscosity of about 2.0 dL / g, it can be extremely difficult to do so. However, many quaternary articles (including, but not limited to, endoscopic agents) can be coated with the polymer blends of this invention. f > to improve- the L9 properties superficial of the article, the preferred surgical items are sutures and surgical needles. The article qu? Most preferred rheumatic is a suture, very preferred added to a needle. Pi efep blernent e, the suture is a synthetic absorbable suture. These sutures are derived, for example, from polymer ovens and lactone monomers such as glycol, laccase, γ-caprolactone, L, -dioxanone, and carbonate of untill, the preferred suture is a suture. The same amount of relaxation that is composed of a polygon and a polygon, as well as a "Ja-co lact ida", the amount of imputation that will be applied to the surface of an intertwined suture can be determined empirically, and will depend of the particular uñero copol- and suture chosen. Ideally, the amount of coating applied on the surface of the suture may vary Lar from about 0.5 to about 10% of that < The coated suture, very suitable from about 1.0 to about 20% by weight, was greatly reduced from about 1% to 5% by weight. If I read the amount of coating in the suture was greater than about 30% by weight, then the risk may increase. r uniente ° e descascare when suture passes through the ejido. The sutures rewaxed with the polymer blends of the invention are desirable because they have a more slippery feel, making it easier for the surgeon to slide the suture knot to the trauma site that is urgently needed. In addition, the suture is more flexible, and therefore is easier to manipulate - during use for the surgeon. These advantages are exhibited in conjunction with sutures that do not contain surfaces coated with the polymer of this invention, In another embodiment of the present invention, when the article is a needle that is urgent, the amount of coating or coating is less than one. The surface of the article is a quantity that has a coffee with a thickness that varies preferably between about 2 to 1 redefined 20 microns on the needle, most preferably "4 to about 8 microns if the amount of coating on the needle was such that the thickness of the coating layer was greater than about 20 milligrams, or the thickness was smaller, of approximately 2 millimeters, then the desired performance of the needle as it passed Through the tissue it can not be achieved.In another form of the present invention, the polymer mix can be used as a pharmaceutical vehicle in a drug release matrix. iz, the polymer blends can be mixed with a therapeutic agent to form the matrix. The variety is wide of different therapeutic agents that can be used together with the Loxaest aliphatic pols of the present invention. In general, therapeutic agents that can be administered by means of pharmaceutical compositions of the invention include, without limitation: finishes such as antibiotics and antivalent agents.; analgesics and analgesic combinations; anorexic; arit i helmi nt i eos; antiarthritics; agents ant lasrnati eos; ant i comvulsi vos; anti-repressive; agents an idiuret cos; ant diarrhea; antiha t minicos; anti-lamatop agents; antigraph preparations; antinausea; 5 antineoplastic; antipark drugs to nsoni but; anti prup ta eos; antisacot LCOS; ant I r r-et I eos; antispasnodics; antics synpat ornaments; xanthe derivatives; Cardiovascular cannons that ancludes canal blockers «Jo calcium and bet aL > loqueadores such as pandolol and LO «ntiar p t mi eos; an < Lhi per ensivos; diuretics; vasodilators that include general, perionea and cerebral coronary arteries; stimulate! s of the central nervous system; Cough and flu preparations, which include decongesting him before; hormones such as tradiol and otos est o roí des, which include cor-t i coostero i des; hypnotics; i nrnunosupresivos; The musculoskeletal elements; paru ° J mput the i t o'-; ps i eoest i mu ant e °; sedatives; and t ranqui 1 i zant e; and natural proteins > or genetic engineering, polscap dos, g I i copí ot ot? na. 1 i poprot ei rias. The matrix of drug release can be added to any form of adequate dose, such as orally, parenterally, subcutaneously as an implant, vaguely or as a suppository, and the formulations of the substance containing the substance may be formulated at the same time. mix- one or more therapeutic agents with a pox loxaost er. ,) the therapeutic agent, may I be present as a liquid, a sol or f orily divided, or any other physical form ')') appropriate Typically, but optionally, the matrix will include or not additives, for example, s? b s t a c i a s a u x 11 i a i? S y no t o i cas t a 1 is like i L ument, vehicles, ex c i t ion, stabilizers or similar. Other suitable additives can be formulated with the mixture of polymer and pharmaceutically active or compound agent, however, if the water is to be used it must be added immediately before administration. The amount of therapeutic agent will depend on the particular drug employed and the medical condition that will be treated. Typically, the amount of drug represents approximately 0.001% to about 70%, more typically from about 0.001% to about 50%, very typical of about 0.001% to about 20% by weight of the matrix. The amount and type of polyoxester incorporated in the parenteral type will vary depending on the release and the amount of the device used. The product may contain mixtures of polyneums that have molecular weights to provide the desired release profile or consistency of a given formulation. The poxaester contained in the mixtures, upon close contact with body fluids including blood or the like, undergo gradual degradation (principally through hydrolysis) with concomitant release of the dispersed drug during an extended period of time. or sustained (as compared to the salinity of an ionic saline solution.) This may result in prolonged release (r • "temple, for more> 1 to 2,000 noras, f > refer 2 to 800 hours) of elective quantities (for example, 0.0001 mg / k / hour to 10 mg / kg / hour) of the drug. This dose urine can be admired as necessary depending on the subject The severity of the affliction, the judgment of the prescribing physician, and if my laws, individual formulations of drugs and polymer mixtures can be tested in appropriate models in vitro and in vivo, will be achieved. desired drug release profiles.For example, a drug can be formulated with a po 1 loxaest or- and orally admired an animal. The drug release profile can then be controlled by appropriate means such as, by taking blood samples at specific times and testing the samples for drug recall. After this procedure or similar, those experts at the ethics will be able to formulate a variety of f or-inulacione. In a further embodiment of) the present invention the polxaest? The polymer blends of the present invention can be used in tissue engineering applications. \ n Support for cells. Suitable tissue framework structures are known in the art such as the prostatic articular cartilage described in the North American palette.

,, JÜb.311, the porous b i odegraduble framework described in WO 9 < ? / 2bU / q, and the prevasculap zades implants described in UO '.3 / U0850 (all incorporated herein by reference).

Methods for seeding and / or culturing cells in tissue frames are also known in the art as those methods described in l_PO 2? 2 9 [SI, WO 90/03785, WO 90/12604 and WO 95/33821 (all incorporated herein by reference). The examples set forth below are for the purposes of the IRA, and are not intended to limit the scope of the problem and to what extent. Numerous additional techniques within the scope and scope of the invention will be clear to those skilled in the art.

Example 1 Preparation of 3,6-dioxaoctanedioic acid dimethyl ester The diacid, acid, 6-ioxaoctanod lo i co, was synthesized by oxidation of triethylene glacol. The oxidation was carried out in a three-necked flask of 500 milliliters with a thermometer, an additional funnel, a gas absorption tube and a magnetic rod of heat. The reaction flask was immersed in an oil bath placed on a magnetic stirrer. For the bottle (Je reaction were added L57..3 ml of a nitric acid solution of hfl%, 37 ..0 g of tiletto gel was added to the additional funnel, the contents of the bottle were heated, at 7 ° C-00 ° C. -1 test containing 0"5 g of glycol and the concentration of concentrated nitric acid was heated in a water bath (to which carbon gases appear to appear.

They were added to the reaction bottle. The mixture was stirred for a few minutes; the glycol was then added carefully.

HQ HO. HNOg OH ^ OH 3,6-dioxaoctanedioic acid triethylene glycol Dimethyl esters of 3,6-dioxaoctanedioic acid The rate of adhesion had to be controlled with extreme care to keep the reaction under control. The adherence rate was low enough so that the 1-to-1 ratio of 1 excretion was 1%. 1 da - \ 70 - 8 ° 0. After it was finished adding (80 ml), the temperature of the leaction mixture was maintained at 7 ° -0 ° C for an additional hour. Rl continued maintaining this temperature scale, the excess of nitric acid and water after distilled under pressure reduced the (suction of water). The residue ti or syrup was cooled; some sounds appeared. The product had the IR and I1N spec (expected for the 1-dicarboxylic acid, the crude product was used as such to be fi xed.) The acidification of the acid 3, dioxaoct crude anodiocio was achieved as follows: To the reaction bottle containing 36 g of the crude diacid, 100 ml of methanol was added, which was stirred for 3 days at room temperature after L5 g of water. The sodium bicarbonate was added and stirred overnight, the mixture was filtered to remove solids, an additional 10 g of sodium bicarbonate was added to the liquid, this mixture was stirred overnight. filtered once more, the liquid was a reactant, and the RfN analysis of the product was mixed with a mixture of d-gland glycollate (70.4 mol%) and t pg the content of inonomethalo (21. ( 5 molar%)., No significant condensation of diacid was observed.

L5 Example 2 Preparation of polyoxaester from the methyl esters of 3,6-dioxaoctanedioic acid and ethylene glycol.

POLY OXA "ESTER 77 A 50 ml glass reactor, mechanically stirred, flame-dried, suitable for the reaction of the pol to condensation, was charged with 20. (2 g (approximately 0.1 mole) of the methyl esters of acid 3, 6-dioxaoctin. "Jel example l, lii.p"? g (0.3 molos) of glycol of the full distillate, and 0.0606 ml of a -elution of 0.33M and stannous octoate in toluene. When the reactor was ventilated with nitrogen, the gradual temperature was increased over the course of 2 hours at 1 ° C. A temperature of 180 ° C. was maintained afterwards.

«Jurante o ras 20 hours; During all these periods, the heating of nitrogen to an atmosphere, the methanol formed was collected. The reaction flask was allowed to cool to room temperature; then it was (encouraged) Slowly under pressure induced (O.Ql? j-l.O min) on the course At approximately 32 hours at 0 °, during this time, samples were collected at "J". conal is A temperature "ib ((C C i i manten manten manten manten ante ante ante 4 4 4 4 4 4 ante ante ante ante Una Una Una Una Una Una Una Una Una Una Una Una Una Una Una Una Una Una Una Una Una Una Una 4 的 r (的 r (的 r (的 r (的 r (r viscos. Se Je Una temperatura 的 r (r viscos 的 r (r r in 0.20 dl / g, as determined in hexa fl uoroi sopropanol (II TP) at 25 ° C or a concentration of 0.1 g. The polymerization continued under reduced pressure with increasing temperature, on the course «le api ox a dame nt o Ib hours, from 160 ° C to 1Ü0" C; a temperature of 180 ° r maintained for 0 hours At the end of the day, a polymer sample is shown at the same time. was discovered or had a 1 ... V. of 0.34 of 1 / g. The reaction continued under reduced pressure for another 8 hours at 1 ° 0 °. The resulting particle has an inherent viscosity of 0.40 dl / g, as determined in HF1P at 25 ° C and at a concentration of tl.l g / dl.

Example 3 Preparation of polyoxaester with 3,6,9-trioxa-ndecanedioic acid and ethylene glycol.

Acid 3,6,9-trioxaun ecanodióico POLY "OXA" ESTERES A 250 milliliter, mechanically stirred, glass-dried reactor, suitable for poly condensation reaction, was charged with 44.44 g (0.2 moles) of acid, b-, t-poxaundecandioic, b2./7 g (lU). moles) of distilled full glycol, and 9.96 mg of di butyltin oxide, after which the reactor is charged, and the nitrogen contents are ventilated with 2 '. of the bottle of water were grlly encouraged under nitrogen to an atmosphere, in about 32 hours, at around 100 ° C, during that time or in the collected water. The reaction mass was allowed to cool to ambient atmosphere. The mass of the reaction was heated under reduced pressure (0.015- LO mm), grlly increasing the temperature to 180 ° C in about 40 hours, during which time additional distillates were collected.Continuous polymerization under reduced pressure while maintaining at 180 ° C dur-ante for an additional 16 hours, the polymer resin antc-e has an inherent viscosity of 0.63 dl / g as determined in HFTP at 25 ° C and a concentration of 0.1 g / dl.

Example 4 Preparation of polyoxaester with polyglycol diacid and ethylene glycol.

HQ t fo- - ° -J-aH HO-CH2-CH2-OH polyglycol diacid (n = 10-12) POLY "OXA" ESTERES A 500 milliliter, mechanically stirred, flame-dried glass reactor (suitable for polycondensation reaction) was charged with L23..Ü g (0.2 mole) of polyacrylate diacid (weight The product of Leader «Je 619), 62. Of g (1.0 mole) of ethylene glycol destabilized, and 9.96 g of dibutyltin oxide. After purging the reactor and purging (ion or nitrogen), the contents of the reaction flask were heated under nitrogen to an atmosphere, grlly increasing the temperature to 200 ° C for about i hours, during this time the water formed was eco-labeled The reaction flask was heated grlly under reduced pressure (0.015 1.0 ml) of ambient temperature to 140 ° F-approximately 24 hours, during which time additional distillates were collected. 10 g was <or auu at this stage, and it was discovered that a foolish IT). (Je 0.14 dl / g in HF I at 25pO, 0.1 g? It.) The continuous polymerization under reduced pressure when heating from 140 ° C to 180 ° C for about 8 hours, and then maintained at 180 ° C (during 0 Additional hours A polymer sample was taken once more and it was found to have an IV of 0.1 μg / g The reaction temperature was then increased to 190 ° C and maintained under reduced pressure for 0 h The additional polymer 1.1 has an inherent viscosity of 0.711 dl / g as defined in HFFP a 2b "C and a concentation of 0..1 g / dl.

Example 5 Polyoxaester / caprolactone / trimethylene carbonate copolymer at 5/5/5 wt.

A bottle with a single round neck at the bottom, of 50 milliliters dried to flame, was loaded with 5 grams of polioxaester aliquot "Je L Example 4 which has a T" V of 0.14 dl / g, 5.0 grams (0.0438 moles) «Je f, -caprolactone, 5.0 grams and 0.049 moles)« Carbonate of t runcet i wood, and 0.0094 ml of a molar solution of 0.33 of oct or to < or the t annoso of t ol ueno. After the scratch was adjusted with a magnetic stirrer, the reactor was purged with nitrogen before the venting with nitrogen. The reaction mixture was heated to 10 ° C and kept at this temperature at 12 hours. The copoLunero was dried under vacuum (0.1 mrn hg to 80"O) for - ~ approximately 16 hours to remove any non-reacted monomer, and the codend has an inherent viscosity of 14 dl / g as determined. in l-IFI at ° C and at a concentration of 0.1 g / l Fl Copol to a viscous liquid, t room temperature The molar ratio of poloxates / POL / PTrlO was discovered by RTIN analysis of 47.83 / 23.t 3 / 8. b.

Example 6 Polyoxaester / caprolactone / glycolide copolymer at 6 / B.1 / 0.9 by weight.

A single-neck flask, round in the lower fiarte, 25 ml, flame-dried, was loaded with 6 grams of the polyester IOX laest of example 4 having a T.V. "Je 0.17? Ll / q", 8..1 grams (0.0731 moles) of f acprol act orna, 0.9 grams (0.008) moles of glycol and 0.0080 ml of a solution of oct oat or stannous molar of 0.33 in toluene The scratch was adjusted with a magnetic stir bar. The reactor was flushed with nitrogen three times before venting with nitrogen. The reaction mixture was heated to 160 ° C and maintained at this temperature for about 18 hours. III «. Opolim or t has an inherent viscosity of 0"2f > dl / g in HFTP at 25 ° C and a concentration of 0.1 g / dl. The copolymer is soldered at room temperature. The molar proportion of aoxaester / PCL / PGH / caprolactane was found by means of a 1 to 9 s RNN of b 6.54 / 37.73 / 3. (9 / 1.94" Example 7 In vitro hydrolysis The pox toxoster of Example 3 was purely hydrolysis in v i t ro at 200 ° C and at reflux temperature. A 100-mg sample of the polysaccharide, placed in 100 ml of a buffer solution "Phosphate (0.2 in. In phosphate, pH" Je 7.27), was completely hydrolazed for about 7 days at 50 ° C, where reflux was Completely hydrolysed «Jurante around Ib hours» Example 8 In vitro hydrolysis The poloxaester of Example 2 was tested for hydrolysis in vitro at 50 ° 0 and at reflux temperature. A sample of 100 mg Jel pol loxaester, placed (in a 100 ml buffer solution (pH 7.7), was completely hydrolysed for about 25 lias at 50 ° C, where at reflux i ue Completely has been drilled during approximately 16 hours.

Claims (8)

NOVELTY OF THE INVENTION CLAIMS 5 1.- A mixture of polymers < That includes poloxa are alafat? cos that have a first divaionte repeat unit of formula T: ro -0 (0) -C (Ri) < 2) -0- < R3) 0 0 (Ri) (R2) -C (0) -1 (1); and a second repetition unit selected from the group of Fói muías consisting of: I "0 LO R-V- IA (TT); r-O-Rs -C (0) -1B (111); (C -O-R5 -0 (0)] P -0-) LG (XI) and combinations of the same, where Ri and R2 are independently hydrogen or an alkyl group containing "1 to 8 atoms" e lime bonus; R3 is a unit of aliLeno that contains 2 to 12 carbon atoms or is a group of Ib ox lalqu filled with the following formula: l "(CH2) c -u- ID - (H2) E - (IV), where C is an integer in the scale of 2 or approximately 5,? Is an integer on ( u scale from about 0 to about 2,000, and E is an integer on the scale of about 2 to about 5, except when]) is zero, 30 in which case E will be an integer from 0 to 12; R4 is a unit to the uileno that contains from 2 to 8 carbon atoms :: (1 is an integer in the scale of L to 2000; Rs so selec of the gr-upo quo co siste of -C (R6) (R7) - , - (H2) 3 -0 -, -OH2-Cl12 -0-CH2 -, 0Rs H - OH2 -, - (0H2) -; -. --ÍCH2) F-0 -0 (0) - y ( 0l-l2> F - C (0) 0U2 -; ey 7 • '&nt; n 2b independently hydrogen or an alkyl containing 1 to 1! carbon atoms »»; Ps is either hydrogen or methyl; F o an environment on the scale «Je 2 to 6; is an integer in the scale of 1 to n so that the molecular weight- number in formula 1T1 is less than about 200,000, preferably less than about 100,000 and most preferably less than 40,000; b P is an integer in the scale of 1 to m such that the number-average molecular weight of the formula XT is less than about 1,000,000, preferably less than about 200,000 and most preferably less than 40,000; 0 represents the residue monkeys from L to L hydrogen atoms of L LU gr-upo hidroxilo of an alcohol that previously has 1 a 200 hydroxyl groups approximately; and
1. I. an integer from about 1 to 200 and a second polymer selected from the group consisting of homopolymer and copolymer of polymers ipoctone with the repeating units described with the Ib formulas ITT and XI, aliphatic polyurethanes, poly methanes of polyethylene, po 1 and polyester urethanes, polyester and liter counting. polyamides, polyvinyl alcohols,? ol? (ox? do of et full), oxide and polypropylene, pol? et? longlicol, pol i ropilengl icol, poli tet umet 1 eno, 0 poLi vi ni 1 pyrro 1 i dona, poliacp lamí da, poL i (hidroxieti l cp lat o), pol i (has «Jroxi et i Lmet ucp lato ) and combinations of the same.
2. 2.- The pollutants are aliphatic according to the definition 1, where the polymer has the formula l ~ - b 0 -0 (0) ~ C (I) (R2) -0- (R3) -0 -0 (R?) (R) 0 (0) - (0 -R4) A - IN, n where M is an integer on the scale from 1 to 10,000, af > ? approximately. 3 b
3. 3. - The polioxaest are aliphatic in accordance with claim l, where the polymer has the form I "(- 0 (0) - 0 (Ri) (R2 -0 -R3 - 0 - 0 (Ri) (R2) - 0 (0) - (0- R4) A ~ 0) S (0 () - Rs -0) B Jw, where 5 b is an integer in the scale from 1 to 10,000 approximatively and W is an integer in the scale from about 1 to 1,000,
4. 4. The polyoxaesters according to claim 1, wherein the polymer has the formula I "(-0 (0) -0 (R?) (R2) -0-R3 - 0-C (R?) (R2) -0 (0) - (0-l-) A -0) s 10 (L-Rs -) 0)] p -0-)? _ 03w; where is an integer in the scale "Je around" Je 1 to 10,000 and U is an integer in the scale "Je approximately one to 1,000. 5 »- A device made of a polymer mixture < It comprises aliphatic polyesters having an Lb first davant repeating unit "Je formula 1: f" 0-0 (0) - C (R?) (R2) -0 (R3) -0-0 ( R?) (R2) - C (0) -] (I); and a second repeating unit selected from the group "le las foi muías < μ,? or consist of: T-O-R ^ -IA (TT); ["-0 -R5 -0 (0) - 1B (? 3T); (Y-O-Rs 0 (0) a> -0-) L0 fj) and combinations thereof, wherein Ri and 20 R2 They are either hydrogen or an alkyl group containing 8 atoms, the carbon, R3 <= "•• a unit of aluil« was with 2 to 12 carbon atoms or a group or ox ia 1 qui le o do the «-iguionte lorrnula. -! ~ (OH2) c -0-1D (0H2) E ~ (TV), --- n where an integer on the scale of 2 to 2b approximately 5, is an integer on the scale «Je around do 0 to approximately 2,000, and F an integer on the scale of about 2 to about 5, except when ü is zero, in which case F will be an integer from 0 to 12; R4 is an alkyl ene unit containing from 2 to 8 carbon atoms: - it is an integer in the scale from 1 to 2000; R5 is selected from the group 5, which consists of -C (R6) (R7) -, (0H2) 3 -0-, CH2 -CH2 -0 -Cl-I2 -, -CRßH- 0H2-, -CH2 - , - (OH2) F - -0 (0) - and (OH2) F-0 (0) -CH2-; Re and 7 are independently hydrogen or an alkyl containing from 1 to 8 carbon atoms; Re is hydrogen or metallo; F- is an integer on the scale from 2 to b; Ti is an integer on the scale of l to n of 10 so that the number average molecular weight of the lower Til os formula- < μ 200,000 approximately, preferably less than about 100,000, and most preferably less than 40,000; Give an integer on the scale of 1 to m in such a way that the average molecular weight in numei or "the photic mule XI is less than Ib 1,000,000 approximately, preferably less than 200,000 approximately and very much less than 40,000; 0 represents the residue less than 1 to L hydrogen atoms of the bi roxyl group of an alcohol which previously contains from 1 to 200 hydroxyl groups approximately and I. is an integer from 1 to 0 200 approximately; and a second polymer selected from the group consisting "Je homopol unoro and copol amero of lactone-type polymers with the repeating units described with the formulas [11 and XI, aliphatic polyurethanes, polyurethanes" le polieter, pol 1 urethanes of polyester, copol irneros of full polyethylene, polyamides, alcohols, pol 1 va n L eo, pol (oxido do «« Eet ileno), polypropylene oxide, poliet 1 lengLicol, pol i propí lenyli col, oxado c e f > ol i tetramef i Leño, pol av i ni 1 pin or 1 idona, poliacp larní du, pol i (hidro iet i lacr ilato), pol t (ha droxiet i l etacp lato) and combinations thereof. 6. The device of consistency with claim 5 further characterized in that the device is in an absorbable surgical device. 7. 1-11 absorbable surgical device in accordance with claim 6 also characterized in that the absorbable surgical device is selected from the group consisting of bandage for burns, hernia patches, medicinal bandages, facial substitutes, gauze, fabrics, sheets, felts , sponges, gauze bandages, arterial graft, bandages for skin surfaces, bra «Je suture knot, pins, fasteners, turn 1 The, plates, insurance, spellings, hooks, buttons, sujot adores, bone substitutes, Intrauterine devices, tubes, instruments < U rurgical, vascular implants, vascular supports, e everal e ver, and artificial skin. 8. p ubsoihible surgical device in accordance with the claim, ": bristle also because the device is a filament. < -) .. - 1 filament of the i et i ndi cation 0, characterized in that the filament is attached to a needle. 10, .- A device coated with a mixture of polymers (was comprised of pol toxaest is ulifatieos < | uo 3 < 1 they have a first divalent repeat unit of formula I. LO 0 (0) -0 (R?) (R2) -0- (R3) -0-C (R) (R2) -0 (0) -] (D; and a second uni «Repeating Jad selected from the group of formulas consisting of: G-0-R «-1A (IT); TO-Rs - (0) - IB ÍTIT); (T -O-RS- b (0) lp -0- 1 | _G (XT) and combinations thereof, wherein Ri and R2 are independently hydrogen or a group of at least 1 to 8 atoms; carbon; R3 is a unit of alkyl ene containing from 2 to 12 carbon atoms or is an oxyalkylene group -the following formula: -H-l-tet-c or-lD-LO (H2) E ~ (IV ), where 0 is an integer in the scale from 2 to approximately 5, 1) is an integer in La (scale of about 0 c? approximately 2,000, and F is an integer in the scale of about 2 to about 5 , except when i) is zero, in which case F is an integer from 0 to 12; R¿ is a unit Ib alkylene containing 2 to 8 atoms "Ue carbon :: fl is an integer on the scale of 1 to 2000; Rs is selected from the group consisting of -C (R6) (R7) ~, - (Cl-I2) 3 -0-, -OH2 -CH2 -O -CH2-, CRβH-OI-I2-, -CCH2U- , ~ (CH2) F- 0-0 (0) - and (0112) F-0 (0) -CH2-; Re and R7 are not independently hydrogen or an alkyl or contains from L to 8 carbon atoms; Re is hydrogen or methyl; F is an integer on the scale of 2 to 6; II is an integer on the Jo l a n scale so that the number average molecular weight of the formula 111 is less than 200,000, | substantially less than about 100,000 and most preferably less than 40,000; 5 P is an integer in the 1 am scale so that the average molecular weight in the formula XT is less than 1,000,000 approximately, preferably less than 200,000 approximate and very much less than 40,000; G represents the residue less than 1 to L hydrogen atoms of the hydroxyl group of an aleono L < ue that previously contains 1 ab 200 hydroxyl groups approximately, and L is an integer from 1 to 200 approximately, and a second polymer selected from the group <? ue consisting of homopolymer and lime-flake of lactone-type polymers with the repeating units described with the ITT and XI formulas, aliphatic polyurethanes, polyurethane or polyester urethane, polyester polyurethanes, copolders « Full polyethylene, polyarnides, polyvinyl alcohols, poly (polyethylene oxide), polypropylene oxide, polyethylene glycol, polypropylene, polyvinyl alcohol tet ra et i leño, pol i vi ni 1 rrol i dona, pol lacp l arn i da, 5 pol i (hi droxiet i lacril to), pol i (h i drox? et i írnet aeri 1 ato) and «ombj nations of ours, where the viscocity? nt r? nsecc > The mixture of polymers is in the range of 0.05 to 2.0 deciliters per gram (dl / g), approximately, measured in a solution of 0.1 g / dL of hexaf Luoroisolespanol (IIF1P) at 25 ° 0. The device coated with the polymers mixture is in accordance with claim 10, characterized in that the device is a suture 12. The device is coated with the polymer mixture of the indicator, characterized by The suture is attached to a needle 13 .. A Drug Release mat that comprises a drug and a polymer mixture containing an eleventh-year-old drug that has a drug. a pr imei-a divalent repetition type of formula I: ro -0 (0) -C (Ri) (R2) -0 - (R3) -0- 0 (Ri) (R2) -0 ( 0) - 1 (I), and a second repetition unit 5 selected from the group of formulas consisting of: f ~ 0 ~ R «- 1A (ID; rO-Rs-C (O) -IB (III ); (l "-0- Re-O (O)] P -0-) LG (XI) and combinations of the same, where Ri and R are ndependi ent ment and a hydrogen group or an alkyl group containing-) from 1 to 8 atoms "Je car-bono; R3 is an alkylene unit that 10 contains from 2 to 12 carbon atoms or is an oxyalkylone group of the following formula: - T (OH2) c -Ü-] D (CH2) E - (TV), where 0 is an environment in which scale of 2 to about 5, D is an integer on a scale of about 0 or about 2,000, and L is an integer on the scale of 15 about 2 to about 5, except when T) is zero, (in which case F will be an integer from ü to 12; "it is an alkyl unit containing 2 to 8 atoms". whole on the scale from 1 to 2000; R5 is selected from the group "? uo with 1 te of - C (Re) (R7) -, (CH2) 3 - -, -CH2 -OH2 - -CH2 -, - 0R8 H 2 OH 2 -, - (CH 2 -, (CH 2) F - 0 - 0 (0) and (OH 2) F 0 (0) - 0 - 1 - 2 - Re and R 7 are independently hydrogen or an alkyl containing 1 to 0 carbon atoms, Ps is hydrogen or methyl, F is an onteium on the 2-year scale, an integer on the scale of 1 an, so that the number-average molecular weight of formula III : > *, is less than about 200,000, preferably less than about 100,000 and most preferably less than 40,000; P is an enter-o on the (scale of L am dc-e ul that the number average molecular weight of the formula XI is less than L, 000, 000 approximately, preferably less than about 200,000 and most preferably less than 40,000 G represents the residue of less than 1 to L atoms of the hydroxyl group hydroxide of an alcohol previously containing from 1 to 200 hydroxyl groups, and L is a (enter-o from 1 to 200 approximately, and a second polymer : the product of the group that consists of homopolymer and flake Lunero "Je polymers ipo lactona with the repeating units described with the formulas TIT and XT, pol i uret nos al if ti eos, poli i uret anos de pol ioter , polyester polyurethanes, copolymers of polystyrene, polymers, polyvinyl alcohols, polyethylene oxide), polypropylene oxide, polyethylene glycol, or 11 p 1 eng 1 i coi, ox i do de poi t te < i -ame t 11 ene, polivini lpp rol tdona, poliacp lamid a, fio Ji (htd oxiot i iucr i lato 1, pol i (hi d o ie i i met acp Lato) and comb i na de i o m i rno s. 14, - The device (Je claim 5 further characterized because the polioxaes are al lf atices have the formula [-0-0 (0) -0 (RI) (R2) -0- (R3) ~ 0 ~ 0 (Ri ) (R2) -0 (0) (0-4) A ~ 1N, where N is an integer on the scale of 1 to 10,000, ap or a dame nt e 1
5. 5 .. - Fl dispositive of The claim nb , also characterized by «the poloxes * you are aLi fatieos t lorien the 1 1 mui a [(- 0 (0) -0 (R?) (R2) -0-K3-0-C (R?) R2) - 0 (0) - (0 - R «) A -0) S (C (0) - Rs - O) B 1 w, in do n of b (it is a (enter-o (at a scale from about 1 to 10,000 and an integer in the range from about 1 to about 1,000. The device according to claim 5, further characterized by the fact that the polyoxestives are fatfined have the formula I (- 0 (0) -C (R?) (R2) -0 ~ R3-0-0 (R?) (R2) -C (0) - (0 -R «) ft-0) s ([-O- R5 - OO) TP 0-) L03W; where 10 b is an integer in the scale of about 1 to 10,000 and W is a (.11 te or in the scale of aproximadament 1 to 1, 000 »17.- E- 1 device coated with a mixture of polyolines according to claim 10, characterized in that the polyesters ali falteres have the formula! ~ -0-0 (0) 0 (R) (R2) - - (R3) - -0 (Ri) (R2) -0 (O) - (0-R4) A-1H, «• 11 where N o uri 'integer e The scale of the 10, 000, uprox iinudament o. 18.- [-1] Device coated with a mixture of polymers according to claim 10, '-) also characterized because the pol toxaest is at i fat j eos t tin the fn r nul ar (-0 (0) -0 (Ra) (R) - -R3 -0-C (R?) (R2) 0 (0) -ÍO-R *) A 0) S (0 (0) Rs -0) B 3W, where b is an enter-o (at a scale of 1 to 10,000 at the same time and U 2b is an integer The scale (from 1 to 1, 000, suitably, L (-) "- The liquid device": is a mixture of polymers according to claim 10, further characterized by the aliphatic polyoxaesters in Formula l "( -0 (0) -0 (R?) (R2) -O-R3 - -OÍRi) (R2) -C (0) - (O-R4) A -0) S (TO R5-0) 0)] P-0-) L0] W; where b is an integer on the scale "Je around" and the 10,000 and Ul is an enter-o (-TI the scale of approximately 1 to 1,000 .20., - the drug release mat of ", on foi I nd with the rei ind cation 13, also characterized by the fact that the polyphexosis aliphatic has the forrnuLu [-0-0 (0) - 0 (RI) (R2) -0- (R3) -0-0 (R?) (R2) "0 (0) - (0 ~ F?) A-TN where N is an enter-o on the scale from 1 to 10,000, approximately 21.- The drug release matrix of condominium with Claim 13, characterized by -.larges Ib because the altyphatic poloxaester has the formula r (-0 (0) -C (R?) (R2) -0-R3-0-0 (R?) (R2) -0 (0) - (O-R) ,) A 0) S (0 (0) RS-0) B1W, where we find an integer on the scale "from 1 to 10,000 approximately" and an integer on the scale "approximately 1,000. 22. The drug release matrix according to claim 13, further car- tepti-ed, because the polosexest aliphatic has the formula [(-0 (0) 0 (Ri) (R2) "- R3"0 -0 (Ri) (R2)" 0 (0) • (0 - R '«) A - 0) sl [-0 RS-0) 0) 1P-0-) LG1W; or where 1 S is an integer on the scale of A around L to LO, 000 and U is a nero ». , - n The o s c a 1 a d a a p r o x a n d a n d 1 to 1, 000.