JPH03501217A - wound dressing - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] wound dressing This invention relates to wound dressings and materials used therein.

Keeping the wound area moist and not allowed to dry may help promote wound healing. Lokoto is recognized. However, poor adhesion of wound dressings When the wound tissue becomes dry and dry due to injury or damage to the dressing after application. , wound exudate adheres to the wound contact layer of the dressing. As a result, the dress Removal of the ring is difficult and painful, and may cause the wound to rupture. These problems are , which is even more serious with respect to dressings made from fibrous or woven materials. Significant trauma can occur with dressings that have a film-like wound contact surface.

As a skin substitute, it has, among other properties, the ability to adhere well to wounds; A method has been proposed that allows for easy scraping without damaging the tissue in the slightest. came. European Patent No. 0091128 describes a thin, tough, elastic hydrophilic membrane. An artificial skin has been disclosed as a synthetic wound cover, and its thickness is 604 m. Below, 2400-80009/m"/24 at 37℃ and 60% relative humidity difference hr water permeability, elastic modulus below 1034N/cwa” (1500Psl) and has an elongation at break of 500% or more. Leave this cover attached and wash it with water. It is taught that it can be removed by

This invention provides a dressing in which the wound adhesive surface has low adhesion to dried exudates. which aims to avoid the disadvantages of known dressings by providing It is. Dressings according to the invention are made from recovered or recovering tissue. , easy to remove by peeling off with minimal and often no wounding Can be done. Something like this has been requested for a long time, but it is possible for the wound* to dry out. This has never been achieved in dressings.

Therefore, the moisture permeability at a relative humidity difference of 10 to 100% when in contact with water vapor is at least Wound pair made of polymer film at 5009/m”/24h/37°C The wound contact surface of the film has an adhesive energy of 30j/m" or less ( provided herein is a low-adhesive wound dressing having a composition (as defined herein).

Adhesive energy as used in this application is defined as the adhesive force between the film and the gelatin substrate. . This adhesive energy (also called "peel energy") is Measured by the method described in Materials, Volume 1 (1986), pages 9-21. , expressed as the θ value in joules per square meter (j/s') at room temperature (22±2° C.).

The desired value of low adhesion energy depends on the internal properties of the film or the wound contact of the film. Controlling the properties of the tactile surface or controlling both properties together It is obtained by

The polymer used in the production of the dressing film of this invention is polyether Polyurethanes, including polyether polyurethanes or polyurethane ureas polyurethane, or polyether polyamide or polyester polyamide It may also be made of polyamide such as polyamide.

In embodiments of the invention, the film-forming polymer includes a moisture-permeable polyurethane; Suitable examples include hydrophilic polyurethanes, which have low mechanical hysteresis properties and Modified to show lysis value. Additionally, the wound contact surface is preferably hydrophobic. stomach.

The hysteresis of the film used for dressing of this invention is -50℃ A dynamic mechanical test method at a frequency of 1 hertz (Hz) in the range ~100°C, e.g. For example, using a polymer laboratory dynamic mechanical analysis analyzer, the length of the dynamic loss angle, kun It is determined by measuring the Zent delta (tan δ).

The peeling energy at temperature T is expressed as: %formula%) (where θ. and S are constants controlled by the surface properties of the film, θ. is the peeling energy at the temperature at which the film exhibits no hysteresis; S is a constant that depends on the thickness of the film. ) It is indicated by.

That is, θ obtained by modifying the surface properties of the film. The value of S is 30j/s" The range of tan δ values related to the adhesive peel energy is as follows:

Suitable hydrophilic polyurethanes for use in this invention have a hydrated water content of about 50% or less, more suitably 10-40%, preferably 15-35%, even more preferably (% of water is the water weight of a polymer immersed in water at 20°C). (calculated based on quantity).

Furthermore, the films used in the dressing of this invention are moisture permeable. It is characterized by a relative humidity difference of 10 to 100 at 37°C and contact with water vapor. Moisture permeability (MVTR) in % of at least 50h/@”/24h, generally 50 0 to 60009/Peng”/24h. Films are appropriate J knee Hough 009/ m" or more, more suitable 1: C has an MVTR of 1100 g/m" or more. good Preferred films have an MVTR of 15009/m” or higher. is measured by the Payne Cup test method (described in European Patent No. 046071). It will be done.

The films used for the dressing of this invention suitably have an opening of 15 to 80μ. thickness, more commonly 20 to 60 μm, preferably 25 to 50 μm It is.

Obtaining low hysteresis values with urethane rubber is not necessarily difficult. molecular hardness A hard segment (geg@ent) separates to form a hard domain (domain). This acts as a crosslink, and the temperature is sufficiently higher than the glass transition temperature (T9). It is fully guaranteed that it will exhibit hysteresis. This film has high moisture permeability. Difficulties arise when this is necessary. This in itself indicates that the hydrophilic soft segment This can be easily achieved by using However, the hard segment is polar (they are bound together by hydrogen bonds) and therefore the hydrophilic soft segments of the molecule. Compatible with other components. As a result, no separation occurs that forms distinct hard domains. No. Rather, phase mixing occurs and the elastomer becomes more like an uncrosslinked rubber. Sea urchin exhibits hysteresis at temperatures higher than the glass transition temperature T9.

The inventors have discovered that hydrophilic polyurethanes suitable for use in the dressings of this invention includes polyester, or more appropriately, polyether polyurethanes or It has been found that polyurethaneureas are included.

The polyether polyurethanes used in this invention include polyols and polymers. Random polymers containing structural units derived from lysocyanates are Appropriate.

Ether units are conceptually ethylene diol, propylene or butylene diol. alkylene diols or triols such as ols or glycerin derived from. Preferably the polyurethane contains one unit of CI, CH, O and -CI l, C1, CIl, 0-1-CBtCH-(CHs)O- or -CHtCH* together with one unit of CIItCHt0. More preferably polyurethane The ether units in are -CEl, CH2O- and C11zCH(CHs)O- or -(CHt)-0- or mixtures thereof, among which poly-CH 2CII(C)Il)0-block is particularly preferred.

In preferred polyurethanes, poly(ethylene) present in the hydrophilic polyurethane glycol) induction block and poly[(propy or buty) glycol] induction block. The molar ratio with the guiding block is 1:1~! =30, more appropriately l:2~1:10 More preferably, the ratio may be changed to 1:2.5 to 1:4. These blocks The molecular weight is suitably between 600 and 60,000, preferably between 900 and 4,000, e.g. 00-2000. Preferred polyols include Britelash Vetro. Liam Chemicals (British Petroleagi Chemical g) Geochemicals commercially available under the trade names of PEG 1500 and PEG 1025. 1' LURACOL TP 440 (1'LURACOL TP 440, commercially available from BASF) Examples include trifunctional polyether polyols such as TP440).

Hydrophilic polyurethanes used as film-forming polymers include 4,4-dife Nylmethane diisocyanate, toluene diisocyanate, 1,6-hexamethi Diisocyanate, 4.4°-dicyclohexylmethane diisocyanate, etc. Diisocyanate residues that are aromatic or aliphatic diisocyanate residues such as includes. Preferred diisocyanates used in the hydrophilic polyurethane of the invention As the salt, 4,4'-dicyclohexylmethane diisocyanate is preferable. and 4.4°-diphenylmethane diisocyanate.

The choice of chain extender for a film-forming polymer influences its internal properties and It was found that this had an effect on the adhesion of the film. For example, ethanediol Conventional chain extenders such as Aliphatic diols, aliphatic diamines or aliphatic aminoalkali containing 4 It is preferable to use coals. αω-diamines such as 1.4-butanediamine films formed from amino-extended polyurethanes have a higher diol content. It has a lower adhesion energy than films made from extended polyurethanes, making it particularly preferred.

The ratio of (number of isocyanate groups): (total number of hydroxyl groups and amino groups present) is Approximately 1=1 must be present to ensure that the isocyanate groups are completely reacted. do not have. However, film-forming polymers are produced by the prepolymer route. If the prepolymers have unreacted isocyanate groups and are Reacts with long-term agents. Unreacted isocyanate groups in such prepolymers The stoichiometric excess of is not more than 5:l on a molar basis, suitably about 2:l. You can.

The adhesive energy of the film material forming the wound contact layer of the dressing is Further reductions can be achieved by implementing other modifications to the film-forming polymer composition. this In such a specific example, a film having an adhesive energy of, for example, 30j/s+” or less is used. Hydrophilic polyurethane film with or without An aqueous component is added. The formulation consists of copolymerizing hydrophobic components with other polyurethane precursors. A single polymer or hydrophobic Mixing or other physical contact with an additive solution consisting of a copolymer containing the components or by other methods.

Contact between two polymers, e.g. a film-forming polymer and an additive, can be achieved by direct mixing. or a polymer solution with hydrophobic additives as a base film in film form. This is done by casting in a casting solution of synthetic polyurethane.

The adhesive energy of the base film is less than about 1003/s', generally about 70J/s'. ＊“Below, but during the production of film-forming polymers or base film formation By incorporating hydrophobic polymer additives into the polymer, e.g. Low adhesion can be achieved by blending before forming. The ingredients of the additive are , e.g. in polymer form and mixed with the base film-forming polymer before film formation. It is preferable that

Therefore, film-forming polymers require incorporation of hydrophobic components before or during polymerization. The hydrophobic component is modified with other polymer precursors in an amount of up to 10% by weight. It is preferable to mix or blend in an amount of . already formed base polymer and When mixing or blending, add hydrophobic component-containing polymer additives to the final polymer. In an amount of 1 to 20% of the mixture or blend, preferably in an amount of 5 to 20% by weight of the mixture It is preferable to use

The present invention comprises a hydrophobic polymer additive in an amount of up to 20% by weight of the polymer blend. Made of a blend with hydrophilic polyurethane, used as a film dressing. The present invention provides polymer compositions suitable for The above additive is a 5-layer polymer blend. Nails with an amount of % or more are appropriate.

Hydrophilic polyurethanes in preferred compositions include polyurethaneureas.

The hydrated polyurethaneurea preferably contains 5 to 50 weight percent water.

Solid additives containing hydrophobic components generally have a glass transition temperature of 40°C or lower, and When used in dressings, water can be easily diffused through the hydrophobic surface layer. Ru.

Preferred additives containing hydrophobic components include polyalkylsiloxanes or their Included are siloxane polymers such as copolymers. Especially suitable siloxane The remer is based on polydimethylsiloxane. Preferred Shiroki Sunpolymer is a block copolymer of polydimethylsiloxane, Polyalkylene glycols such as lene glycol, polypropylene glycol or more preferably polyethylene glycol and polypropylene glycol Contains a mixture of Suitable polyalkylsiloxane used in additive manufacturing Xane/polyalkylene glycol block copolymer from Petrage Chemica It is commercially available from Petrarch Che+aicals.

A suitable additive to blend with the base film-forming polymer is polydimethylsilane. Polyalkylsiloxanes such as xane are combined with polymers such as polyethylene glycol. Block terpolymer capped with real kylene polyol and polyurethane It is an additive.

The inventors also found that when the hydrophobic component is copolymerized with other film-forming polymer components, is used when blending a hydrophobic component-containing polymer with a film-forming base polymer. , hydrophobic components tend to migrate to the surface of the cast polymer or blend. I discovered that. This movement of non-leachable hydrophobic components causes the base polymer to The adhesion energy of films formed with mer is further reduced.

A dress having a wound surface layer of polyurethaneurea modified according to the invention adhesive energy is less than 30j/s", generally less than 2037s+", and It is preferably less than loj/@'. Modified by incorporation of siloxane polymer Dressings produced with polyurethane urea Preferably, the adhesive strength is about 337 m''.

The polymers used in the dressing according to this invention may be polymerized by bulk solution polymerization or reaction polymerization. It can be manufactured by conventional polymerization techniques such as reaction molding. Similarly for making dressings A known casting method is used to manufacture the film used.

The dressings of this invention are used as adhesive dressings, and can be used as adhesive dressings. agents, such as pressure-sensitive adhesives, and are used in medical applications. Suitable adhesives include: Acrylic adhesives (e.g. described in British Patent Specification No. 082070631) and vinyl Adhesives based on nyl ethers (e.g. British Patent Specification No. 1280631 (composition (described in item “A”)).

One type of adhesive dressing is to apply a continuous or puttered adhesive around the periphery. It consists of a single piece of bomber film coated with a thin film. i.e. in the dressing Place the uncoated area of the heart over the wound and place the coated area on the health surrounding the wound. Adheres to skin.

In other embodiments, the adhesive dressing is applied over the entire body-facing side of the film. It has a pattern-cast coating of adhesive. Glue pattern dots , stripes or net-like structures. i.e. dressing area are closed with adhesive, but open areas of the dressing cover the entire surface of the dressing. approximately 90%, generally 60-70%.

Further, in the pond embodiment, the dressing is comprised of a single polymeric film; Adhesive tape is glued over the edge of the side of the film that does not come into contact with the body, and its adhesion Agent coated protrusions extend beyond the edges of the film. Suitable for medical use Hypal and Hybalfix (Hypal) are suitable adhesive tapes. Examples include commercially available products under the trade name ypafex.

Other applications include a simple film to cover burns, bed sores, etc. This includes the use of absorbent dressings with a larger total surface area. Excess exudate is allowed to leak out at the edges in order to contain it. Therefore, the wound contact The absorbent layer can be replaced again and again without disturbing the film. The film itself is Once the wound begins to heal, it can be replaced without rupture or pain. be Alternatively, the film may be perforated to allow excess exudate to drain into the absorbent covering. can be done.

The above holes are arranged at irregular intervals to reduce the effect of adhesion at these discharge points. It can also be a pinhole.

Dressings according to the invention are suitable for use on wounds such as burns, bedsores, surgical sites or skin grafts. It can be used to cover wounds or wounds caused by disease or mechanical trauma. Wear.

Therefore, skin injuries on the animal's body can be cured by applying the dressing of the present invention. Wear.

The dressing of this invention is packaged and sterilized using conventional methods, such as ethylene oxide sterilization. It may also be sterilized. The dressing of this invention can be used as an adhesive dressing. If necessary, the adhesive surface may be covered with a removable protective paper.

The invention will be illustrated by the following examples.

Example 1 The composition of the linear polyurethaneurea base film consists of dichloromethane and t-butane. The presence of di-n-butyltin dilaurate (Tl*) as a catalyst in the mixture of Currently, polypropylene glycol (PPG 1025) 3 mole polyethylene Glycol (PPG 1500) 1 mol 1.4-diaminobutane 6 mol hexamethylene diisocyanate (Desmoto Wool W) Manufactured by polymerizing 10.46 mol of components.

The additive block terpolymer (terpolymer) consists of the following components: Xane/PEG-block copolymer diol (Petradi siloxane diol) Molecule file 70) Butane-1,4-diol 0.015 Moldesmoto ru W 0.035 thousand ru TI! Catalyst 0.050 mol It was produced by bulk polymerization of The film is made of dichloromethane with the above additive polymer. Add Tan/INS (5:4v/v) to make a 25% solution, and add this to the above base. The terpolymer is mixed with a dichloromethylene/l-butanol solution of the polymer. It was manufactured at a concentration of 8%. The mixture was then cast onto release paper and allowed to dry. Got the film.

Attach the film to the gelatin model as a unitary film dressing and Journal Iso Clinical Materials (J, Cl1nteal Mate Adhesive energy of 20j/m' or less at the test site using the method described in Volume 1 showed ghee.

Example 2-8 Polyethylene glycol (PE01500), polypropylene glycol (P PG 1025), butanediol, desmotowool W and molecule fi9500 or from 5900 terminal monohydroxy polydimethyl/siloxane (PDMS) A solution of the polymer precursor in a dichloromethane/l-butanol mixture, was manufactured. The amount of both glycols and the amount of siloxane are varied as shown in the table below. while maintaining constant amounts of 3 mol and 1 mol, respectively. butanediol and des The amount of Motowool W maintains a total NC010)I ratio of 1.1:1.0 I adjusted it as follows.

The reactants were polymerized in the presence of di-n-butyltin dilaurate catalyst. Then Po The reamer solution was cast onto release paper and dried to obtain a film.

Gelatinize film sample as one unitary film wound dressing J C11nical Materials.

Adhesion energy was measured by the method described in Volume 1, (1986) pages 9-2I. It was. The following table shows the adhesive energy values.

Examples 2 and 6 are presented for comparison purposes only.

Example number 1'DMs ffi Adhesive energy (molecular weight) Weight % j/@ ” (Average value) 3 9500 0.1 25 4 9500 1.0 22 5 9500 5.0 10 7 5900 0.1 29 8 5900 1.0 25 9 5900 5.0 14 A film-forming polymer containing a siloxane hydrophobic component was added to PEG 1500 ( molecule! 11565) 15.90g, PPG 1025 (molecular weight 987) 29 ．． 619, Pluracol 440 (triol with molecular weight 490) 0.229, Mol Hydroxyhexylpolydimethylsiloxane (+3000 to molecule 5) 390 y and 31.4 g of Desmoto Wool W were mixed and reacted, and then the reaction mixture was TI! Produced by heating at 90°C for 2 hours in the presence of a catalyst to obtain a homogeneous prepolymer. Ta.

The prepolymer was dissolved in dichloromethane (Loom) while cold.

While maintaining the temperature of the prepolymer solution at 35°C, add 5.2% of 1,4-diaminobutane. 99 isopropanol 100yQ solution was added and the resulting mixture was stirred and refluxed for 2 hours. did.

A highly viscous polymer solution with a solids content of 25% v/v was obtained. This polymer was cast onto silicone-coated release paper at a coating weight of 40 g/s. did. After annealing at 60°C for 4 hours, a gelatin peel test was performed and the following values were obtained: It was.

Top surface -25j/ Bottom surface -23j/@” Each concentration of polysiloxane residue and triol residue in the polymer is 4. It was 52.0.26% by weight.

Example! 1 The ratio of precursors was varied by increasing the triol residue content to 2.12% by weight. The method of Example 10 was repeated except that

The amounts of reactants are as follows.

Desmoto Wool W 30.89 Blue Lacol T P 440 1.85FDMS-OH3,90 P　E　G　1500　16.80 P P G 1025 29.61 1.4-diaminobutane 5.25 The cast film θ values were as follows.

Top surface -13j/s' Bottom -28j/Fog 1 cold storm sail 12 Except for using the base film-forming polymer in an amount of 11.67 moles of Desmotowool W. was prepared as described in Example 1.

A number of samples of the base polymer were taken and each sample was coated with the system described in Example 1. Blend the loxane-containing polymer additives in amounts of 0.5, 1.5 and 10% by weight. Ta. One of the samples was a control sample containing no additives.

Blending is done by mixing the two polymers on a roller conveyor to create a homogeneous A blend was obtained. Place each blend and control in a thin film on silicone release paper. (40±29/-″), air-dried, and annealed at 60°C for 4 hours. . Control sample and 0.5. Samples with 1 and 5% additives Tested with the lower side of the film facing gelatin on a latin model. More support The samples were aged at 55° C. for 1, 2, 4 and 8 weeks, respectively. each brain In addition, samples of each blend were packaged and dressed for early and late aging. The θ value after sterilization using ethylene oxide sterilization, which is commonly used for sterilization of Shown below.

Example 13 The chain extender used in polyurethane base films is °,1,4-diaminobutylene. The method of Example 12 was repeated except that 1,2-diaminoethane was used instead of ethane. I returned it. Blends containing 5 and 10 wt% additives were prepared and cast. Filmed, annealed and tested. θ of film with 5% additive The value was 13.29, and the θ value of the film with 10% addition was 6.35. Attachment The θ value of the control sample containing no additive was approximately 70.

Example 14 A) Film-forming polymers can be produced by a one-shot polymerization method, Lipropylene glycol (PPG 1025) 18.429 and polyethylene glycol Melt Coal (PEG 1500) 9.83y, Desmoto Wool W2B, 519 and T'1. The reaction was carried out at 90° C. for 1 hour in the presence of a catalyst. prepolymer - Add 3.229 butane-1,4-diol until the reaction material becomes solid. After stirring vigorously, the mixture was cooled to 60°C. The obtained solid material was further heated at 90℃ for 2 hours. harden for a while, then dissolve in a mixture of industrial denatured alcohol and dichloromethane, It was made into a 25v/v% solution. Cast this solution into a film, dry and anneal After that, it was cut into 7x7cm dressings.

B) Example! producing a second film-forming polymer by the method described in 7. I made it into a 7cm x 7cm dressing. The amount of additive polymer in the final film is approximately 10 parts The amount was %. Wound dressings are made from squares of film and Apply a strip of Hyparix pressure-sensitive adhesive tape on opposing edges. The adhesive side of the tape extends beyond the edge of the film. did. Place 4 layers of gauze on top of the film part of the dressing, and Supported with Hyperfix tape on the back or top side.

A 5X5 cm partially enlarged wound on the flank of a pig was treated with Polymer A (control) and Covered with a dressing made from polymer sun. For each type of dressing Six types of tests were conducted.

The dressing was removed after a certain period of time.

When the dressing was removed after 2 days, the wound appeared generally healthy with only a few small wounds. It was just a case of bleeding. When the control dressing was removed after 4 days, the fill Several wounds were damaged due to dry exudate adhering to the surface of the wound.

When the dressing made with Polymer B was removed, the dried exudate layer remained intact. The remaining.

After 6 days, when I tried to remove some control films, the films tore. Some of the dressing remained attached to the dry wound surface. Poly For dressings made with Mar B, all dressings were completely non-adhesive. The dried wound exudate layer remained intact.

international search report -renal sentinel-mMla-mcah@11I+11PCT/GB8B10O667 International Investigation report

Claims (23)

[Claims] 1. The polymer film is brought into contact with water vapor at 37°C with a relative humidity of 10-100%. The differential moisture permeability of the film is at least 500 g/m2/24 h, and The wound contacting surface has an adhesive energy (as defined herein) of 30 i/m2 or less A low-adhesion wound dressing having a wound surface layer consisting of. 2. The dressing according to claim 1, wherein the adhesive energy is 20j/m2 or less. 3. The dress according to claim 1 or 2, wherein the film polymer comprises polyurethane. Ng. 4. 4. A dressing according to claim 3, wherein the polyurethane is a hydrophilic polyurethane. 5. According to any one of claims 1 to 4, the film is made from a polymer blend. Dressing as described. 6. Is the blend a film-forming hydrophilic polyurethane and a hydrophobic polymer additive? 6. The dressing according to claim 5, comprising: 7. A dressing according to claim 5 or 6, wherein the additive comprises a siloxane polymer. . 8. The siloxane polymer is a block copolymer of polyalkylsiloxane Dressing according to claim 7. 9. Block copolymer is polyalkylsiloxane, polyalkylene polyol and a terpolymer of additives having residues derived from polyurethane. The dressing according to item 8. 10. Claims 6 to 9, wherein the additive is present in an amount of 5 to 20% by weight of the polymer blend. Dressing as described in any one. 11. Any one of claims 3 to 10, wherein the polyurethane is a polyurethaneurea. Dressing as described. 12. A dressing according to claim 11, wherein the urea moiety is derived from an αω alkylamine. Ng. 13. 13. The dressing of claim 12, wherein the amine is 1,4-diaminobutane. 14. When the blend is formed into a film, it has a surface energy of 100 J/m2 or less. a film-forming base polymer having a The dressing according to any one of claims 5 to 14, comprising a blend with an additive. Gu. 15. Claims that the adhesive energy of the base polymer film is 70j/m2 or less The dredge render according to item 14. The moisture permeability in contact with water vapor at 16.37°C and a relative humidity difference of 10 to 100% is 1. 500g/m2/24h or more according to any one of claims 1 to 15. dressing. 17. Any one of claims 1 to 16, having a body contact surface coated with a pressure sensitive adhesive. Dressing as described in 1. 18. 18. The dressing of claim 17, wherein the adhesive is on the periphery of the dressing. 19. The adhesive passes as a discontinuous coating over substantially the entire surface of the wound contacting surface. 18. The dressing of claim 17, which is cast into turns. 20. 20. The dressing of claim 19, wherein 90% or less of the wound surface is adhesive-free. Thing. 21. A hydrophilic polyester in which the hydrophobic additive is less than 20% by weight of the polymer blend. Claims 1-1 comprising a blend of urethane and a compatible hydrophobic polymer additive. 21. The polymer composition for use in the film-like dressing according to any one of 20. 22. 22. A composition according to claim 21, wherein the polyurethane is a polyurethaneurea. 23. Additives include polyalkylsiloxanes, polyalkylene polyols and polyurethanes. 23. The composition according to claim 21 or 22, which is a block terpolymer of lettane.