GB1586182A

GB1586182A - Adhesive compositions suitable for application to the skin and surgical products incorporating same

Info

Publication number: GB1586182A
Application number: GB9326/77A
Authority: GB
Original assignee: Individual
Current assignee: Individual
Priority date: 1977-03-04
Filing date: 1977-03-04
Publication date: 1981-03-18
Also published as: SE8304112L; JPS53109538A; DK149734C; ES469762A1; DK148408B; JPS6142755B2; SE8304112D0; ATA148178A; FR2400907A1; FR2400907B1; FR2390171A1; DK597483A; DK597483D0; DK149734B; DK149733B; ATA312679A; DK405380A; DK148408C; DK149733C; BE864568A

Abstract

Adhesive preparations for medical purposes contain a gelatinous mixture of a poly(lower alkyl) methacrylate, a physiologically acceptable liquid plasticiser, an inert, particulate filler and a chlorinated rubber. Medical auxiliaries contain adhesive preparations of this type. The adhesive preparations are prepared by mixing the components of the preparation and allowing the resultant paste to be converted into a homogeneous gelatinous preparation at elevated temperature.

Description

(54) ADHESIVE COMPOSITIONS SUITABLE FOR APPLICATION TO THE SKIN AND SURGICAL PRODUCTS INCORPORATING SAME (71) I, JOHN RHODES, a British Subject, of 25 Nant Fawr Road, Cyncoed, Cardiff, Wales, do hereby declare the invention for which I pray that a patent may be granted to me, and the method by which it is to be performed, to be particularly described in and by the following statement: This invention is concerned with surgical products and materials suitable therefor.

More particularly it is concerned with an adhesive composition which inter alia is useful for adhering surgical products to an animal body.

It is often necessary to make an adhesive bond to an animal body, usually a human body, in order to attach a surgical product or device. Although many adhesive compositions are known, very few of these are suitable for application to human skin. The requirements for such an adhesive are stringent; it must bond strongly to human skin, yet be peelable without damage to the skin's surface. Furthermore it must cause no inflammation, even on prolonged contact, and should have a minimal tendency to provoke allergy. It must be free of any substances which may be carcinogenic. The requirement to be non-allergenic is particularly difficult to meet, and most adhesives currently available are prone to cause allergies in a significant proportion of patients.

When the patient has a tendency to allergy, it may be necessary to test a number of adhesives before one is found which is compatible. This is time-consuming for the doctor and in the meantime the patient is caused distress by allergic reactions.

One aspect of this invention provides an adhesive composition comprising a gelled mixture of: (i) a poly (C, álkyl) methacrylate, ii) a physiologically compatible liquid plasticizer, (iii) an inert particular filler, and (iv) a chlorinated rubber.

A preferred poly (C álkyl) methacrylate polymer is polyethyl methacrylate. The poly (C1 álkyl) methacrylate is a brittle solid, preferably having a molecular weight in the range 50,000-1,000,000, more preferably in the range 100,000-500,000, e.g.

about 200,000.

The plasticizer component is a liquid which is physiologically compatible and serves to plasticize the poly (Cl álkyl) methacrylate. A preferred group of plasticizers are ester plasticizers, particularly esters of dicarboxylic acids. Although diesters of aliphatic dicarboxylic acids may be found with suitable properties, we prefer diesters of aromatic dicarboxylic acids, especially phthalate diesters. The alcoholic components of such phthalate di esters may e.g. be selected from alkanols, alkoxycarbonyl-substituted alkanols and aralkanols. The alkanols may e.g. have 1-8 carbon atoms and be optionally substituted by a (C, álkoxy) carbonyl residue. A plasticizer which is particularly satisfactory in all respects is butyl phthalyl butyl glycollate.

This compound is currently available from Monsanto as "Santicizer B16". Other phthalate diesters which can be used include butyl benzyl phthalate, also available from Monsanto as "Santicizer 160". "Santicizer" is a registered Trade Mark.

Another group of plasticizers of interest for use in this invention are N-substituted arylsulphonamides. The aryl residue may e.g. be phenyl optionally substituted by C álkyl, e.g. tolyl. The N-substituent is preferably C, álkyl. An example of such a plasticizer is N-ethyl-o,p-toluenesulphonamide, available from Monsanto as "Santicizer 8".

The precise chemical nature of the plasticizer is not critical to the invention, but it must be physically compatible with the other components of the composition and it must also be physiologically compatible. So far as possible, it should be non-allergenic.

Approval by the FDA for inclusion in foodstuffs and pharmaceutical preparations is a good indication that a substance is physiologically compatible.

The inert particulate filler serves to stabilise the composition in the form of cohesive gel. The filler also reduces the tackiness of the composition, and the proportion and nature of filler should be selected to produce the degree of tackiness required.

Without any filler, the tack is very aggressive and the adhesion to human skin is difficult to break without damage to the skin.

The preferred filler is silica. The filler is preferably of colloidal particle size. Other fillers include finely divided calcium carbonate, kieselguhr, and silicates such as powdered glass, especially barium glass, lithium aluminium silicates or talc.

The chlorinated rubber improves the tackiness and cohesion of the composition. Preferred chlorinated rubbers are highly chlorinated hydrocarbons such as the highly chlorinated polyisoprene available from Imperial Chemical Industries as Alloprene 20 (Alloprene is a registered Trade Mark).

The proportions of the various components in the composition, per 100 ml of a plasticizer, may e.g. be as follows: poly (C,.,alkyl) methacrylate 16-84 g, prefer ablv 20-45g; filler 6-16 1 referably8-12; and 20-4 chlorinated rubberfi-67 g, preferabivy 20-40 g. The relative proportions of the components should be adjusted within these ranges to give products with the desired properties. Optimum relative proportions for any particular desired combination of properties can be determined by simple experiments.

The composition may be prepared by dispersing the poly (C, álkyl) methacrylate, in powder form, in the plasticizer and causing or allowing the powder to dissolve in the plasticizer to form a gel. The filler and the chlorinated rubber may be added at any stage, preferably while the viscosity is still low enough to enable thorough mixing. In a preferred mixing procedure, the filler is mixed with the plasticizer, the poly (C, alkyl) methacrylate is then added, and finally the chlorinated rubber is added.

The mixture is initially a stiff paste, which converts to a homogeneous gel as the plasticizer dissolves the poly (C, álkyl) methacrylate. This conversion proceeds slowly at room temperature and is accelerated by heating, e.g. to 40-800C. Higher or lower temperatures can be used where convenient.

At 60"C, the conversion may typically be completed in about 4 to 5 hours. The conversion time depends largely on the state of sub-division of the poly (C l álkyl) methac- rylate. Preferably this material is in the form of powder in the range 50-400 mesh (British Standard Sieve), preferably below 200 mesh.

After conversion, the composition is a translucent flexible gel of rubbery consistency and tacky to the touch. It has good adhesion to human skin. The material is stable; that is to say, it remains cohesive, does not flow at higher filler concentrations and retains its tackiness and adhesivity over long periods of storage and use.

It is often convenient to gel the composition in situ on a surface to be rendered adhesive. Alternatively the composition may be spread, prior to conversion, on a surface having a release coating and gelled in the form of a layer which can subsequently be laminated onto the article to be rendered adhesive. Another way of applying the composition is by forming a dispersion of the composition in an organic solvent which dissolves all components of the composition except the filler, e.g. a chlorinated hydrocarbon such as chloroform or methylene dichloride, applying the dispersion to an article to be rendered adhesive, and evaporating the solvent. Other suitable solvents include lower aliphatic ketones, e.g.

acetone; aliphatic ethers, e.g. diethyl ether; and C, álkanols, e.g. ethanol. Often it will be preferred to avoid the use of a solvent, because some patients exhibit allergic reactions to common organic solvents. Thus it may be preferable to roll the composition in paste form into a thin layer between surfaces having a release coating, and apply the composition to the article to be rendered adhesive, either before or after conversion of the mixture to a gel.

The composition has a wide variety of applications as an adhesive, particularly but not exclusively for application to human skin as part of surgical products (sometimes known as hospital supply products), e.g. as the adhesive coating of surgical tape and other medical and surgical dressings, coverings and appliances. Such surgical tape or dressing will comprise a flexible substrate bearing the adhesive of the invention on one face thereof. The substrate may be of fabric or plastics film, especially microporous plastics film. When a medicated dressing is required, the medicament may be incorporated in the adhesive. Examples of such medicaments include antibiotics, antiseptics, coal tar derivatives (which are of value in certain dermatological conditions) and antiinflammatory compounds, e.g. steroids.

Such dressings may be used for covering wounds or other damaged areas of skin, e.g.

leg ulcers such as varicose ulcers. For such applications the adhesive has the merit of not adhering in the presence of water. Thus if a dressing is used to cover a damaged and weeping area of skin, it will not adhere to the damaged area but will only adhere to undamaged skin around the periphery.

A particularly advantageous use for the adhesive of the invention is for securing the pouch of an ostomy appliance to the skin around the stoma of a patient. After an ostomy operation, e.g. ileostomy, colostomy or ureterostomy, the patient is left with a stoma through which waste material is discharged. The discharge is collected in a pouch, which is periodically replaced. It has been a matter of considerable difficulty to secure the pouch to the patient in a comfortable but leakproof manner.

Thus another aspect of my invention provides an adhesive element for securing the pouch of an ostomy appliance to the skin around the stoma of a patient comprising a flexible pad having an aperture through which said stoma can pass, a face of said pad bearing an adhesive composition according to the present invention. The other face may be integral with a wall of the pouch, or the pouch may be attached thereto by any suitable mechanical means, such as by an adhesive.

The pad, which will generally be in the form of a disc having a central aperture, is preferably of plastics material. Suitable plastics materials include plasticized acrylic polymers and plasticized vinyl polymers such as plasticized PVC. Since portions of the pad may come into contact with the patient, it is advisable that the pad should be made of a material which is not liable to provoke any adverse reaction by contact with the human body. In articular the material should preferably be non-allergenic.

Suitable plastics materials may be selected from those used in the dental field. Any accelerator (e.g. tertiary amine, peroxide or quinone) used to cure the composition forming the pad should be selected with particular care from this point of view. It may be preferable to cure the composition by exposure to actinic radiation (UV or visible light).

It is preferable for the portion of the pad surrounding the aperture to be relatively stiff while the peripheral portion is more flexible. These conditions may be secured by increasing the thickness of the pad over a central area, and/or by including one or more stiffening webs surrounding the aperture. However the pad as a whole should be sufficiently flexible to avoid discomfort to the patient and to conform closely to the curvature of the abdominal wall.

In a particularly preferred embodiment, the aperture in the pad, on the face to be adhered to the patient, is surrounded by a layer of hydrophilic gum which swells on contact with water. This is preferably contained in a moat between two upstanding webs formed on the pad. The hydrophilic gum which I prefer is karaya gum. In the presence of fluid seeping from the stoma, karaya gum will take up water and swell.

The swollen gum provides a good seal to the abdominal wall, and will effectively prevent further fluid from leaking out peripherally.

This mechanism protects the adhesive of the invention from moisture.

Instead of karaya gum, other natural or synthetic swellable hydrophilic gums can be used, e.g. agar, alginates or a suitable grade of polyvinyl alcohol.

The other face of the pad may be formed integrally with the ostomy pouch, or the pouch may be attached by any appropriate mechanical means such as clips or more preferably by adhesive. This face of the pad does not come in contact with the skin, and any suitable adhesive can be used. It is not necessary for this adhesive to be physiologically compatible, although the adhesive of the present invention may often be quite suitable for the purpose.

The adhesive of the present invention, in the form of a cohesive sheet, may extend beyond the periphery of the pad and the exposed face of the adhesive sheet may assist in securing the pouch to the pad. If not used for this purpose, it is preferable to render this exposed face, and the edges of the adhesive sheet, non-tacky to avoid adhesion to clothing and the like.

According to a preferred embodiment, the pouch or bag for collecting the discharge from the stoma may be replaced without removing the pad from the patient. This avoids having to tear the whole device from the patient each day. This embodiment is particularly applicable to colostomy appliances. In this embodiment the pouch is preferably secured to the pad by a contact adhesive.

The device described above is particularly useful for ostomy patients but may also be of value for collecting a fistular discharge. If desired, the pad may include means for attachment to a belt, e.g. in the form of apertures or projections on opposite edges of the pad (or at opposite ends of a diameter when the pad is circular) for attachment to corresponding fixing means on the ends of a belt.

An embodiment of the invention will now be described by way of example with reference to the accompanying drawing, which illustrates an adhesive element according to the invention in cross-section.

Referring to the drawing, the abdominal wall 1 of a patient has been surgically provided with a stoma 2. The adhesive element according to the present invention comprises a disc 3 of plastics material having a central aperture 4. The aperture 4 is surrounded by two concentric webs 5 and 6 forming a moat in which is situated a ring of karaya gum 7. The outer portion of the disc is adhered to the abdominal wall by a sheet of adhesive 8 having the composition given below. The other face 9 of the disc is available for adhesion of the pouch or bag appropriate to the discharge to be collected.

The composition of the adhesive is as follows; "parts" have the relation of ml to g for liquids and solids respectively: Butyl phthalyl butyl glycollate 6 parts Polyethyl methacrylate 2 parts Alloprene 20 2 parts Colloidal silica 0.65 parts The butyl phthalyl butyl glycollate is currently available from Monsanto as Santicizer B16. Otherwise it can be made by standard esterification procedures.

Polyethyl methacrylate was in the form of a powder below 240 mesh (British Standard Sieve) and had a mean molecular weight of about 200,000. It was obtained from ADI Plastics Limited, Marton, Blackpool, England.

The Alloprene 20 is a chlorinated polyisoprene, available from Imperial Chemical Industries, (Alloprene Section), Runcorn, Cheshire, England.

The silica was a pharmaceutical grade having a low iron content.

The silica was first mixed with the butyl phthalyl butyl glycollate, and the polyethyl methacrylate and Alloprene were added in turn. A very viscous paste resulted, which was mixed mechanically. The paste was then rolled out between two sheets of siliconcoated paper to a thickness of approximately 1.5 mm and allowed to convert for 6 hours in an oven at 60"C.

After cooling, the adhesive was in the form of a cohesive, extremely tacky sheet which could be cut to the desired size and shape. This adhesive is highly compatible with the human body. Indeed, we have never yet observed any adverse reaction to it, even in patients who are allergic to many conventional medical adhesives. Although I cannot say that this material will never cause allergy, it appears to be superior in this respect to most known adhesives. The adhesive projects some way beyond the disc 3 in order to assist in keeping the device in good contact with the abdominal wall.

Another adhesive composition is as follows: Butyl benzyl phthalate 6 ml Polyethyl methacrylate 2 g Alloprene 20 2 g Colloidal silica 0.5 g The polyethyl methacrylate was the same as used in the first adhesive. The mixing and conversion procedure was as described.

The disc was composed of an acrylic copolymer which was made as follows. 16 parts of the polyethyl methacrylate described above were mixed with 10 parts of a liquid mixture having the composition 2% N,N-dimethyl-p-toluidine; 30% ethylene glycol dimethacrylate (available from Rohn & Haas); and 68% of butyl phthalyl butyl glycollate.

The resulting fluid slurry was immediately poured into a mould and cured for 15 minutes at 60"C to form a flexible, rubbery disc. The accelerator (N,N-dimethyl-ptoluidine) may be replaced by other suitable tertiary amines, but it is preferable to select this material with care to avoid allergy problems.

WHAT I CLAIM IS: 1. An adhesive composition comprising a gelled mixture of: (i) a poly (C 1 álkyl) methacrylate, (ii) a physiologically compatible liquid plasticizer, (iii) an inert particulate filler, and (iv) a chlorinated rubber.

2. An adhesive composition according to claim 1 wherein said poly (C,.,alkyl) methacrylate is polyethyl methacrylate.

3. An adhesive composition according to claim 1 or 2 wherein said poly (C, álkyl) methacrylate has a molecular weight in the range 50,000 to 1,000,000.

4. An adhesive composition according to claim 3 wherein said molecular weight is in the range 100,000 to 500,000.

5. An adhesive composition according to any of the preceding claims wherein said plasticizer comprises a phthalate diester.

6. An adhesive composition according to claim 5 wherein the alcoholic components of said phthalate diester are selected from alkanols of 1-8 carbon atoms optionally substituted by an alkoxycarbonyl residue, and aralkanols.

7. An adhesive composition according to claim 5 wherein said plasticizer is butyl phthalyl butyl glycollate.

8. An adhesive composition according to claim 5 wherein said plasticizer is butyl beuzyl phthalate.

9. An adhesive composition according to any of claims 1-4 wherein said plasticizer comprises an N-(C, 4-alkyl) arylsulphonamide.

10. An adhesive composition according to claim 9 wherein said plasticizer is N-ethyl-o,p-toluenesulphonamide.

11. An adhesive composition according to any of the preceding claims wherein said inert particulate filler comprises colloidal silica.

12. An adhesive composition according to any of the preceding claims wherein said chlorinated rubber is a highly chlorinated polyisoprene.

13. An adhesive composition according to any of the preceding claims comprising, per 100 ml of plasticizer, 16-84 g of poly (C, álkyl) methacrylate; 6-16 g of said filler; and 16-67 g of chlorinated rubber.

14. An adhesive composition according to claim 13 comprising, per 100 ml of plasticizer, 20-45 g of poly (C, álkyl) methacrylate; 8-12 g of said filler; and 20-40 g of chlorinated rubber.

15. An adhesive composition according to any of the preceding claims including a medicament.

16. An adhesive composition according

**WARNING** end of DESC field may overlap start of CLMS **.

Claims

**WARNING** start of CLMS field may overlap end of DESC **. Polyethyl methacrylate 2 parts Alloprene 20 2 parts Colloidal silica 0.65 parts The butyl phthalyl butyl glycollate is currently available from Monsanto as Santicizer B16. Otherwise it can be made by standard esterification procedures. Polyethyl methacrylate was in the form of a powder below 240 mesh (British Standard Sieve) and had a mean molecular weight of about 200,000. It was obtained from ADI Plastics Limited, Marton, Blackpool, England. The Alloprene 20 is a chlorinated polyisoprene, available from Imperial Chemical Industries, (Alloprene Section), Runcorn, Cheshire, England. The silica was a pharmaceutical grade having a low iron content. The silica was first mixed with the butyl phthalyl butyl glycollate, and the polyethyl methacrylate and Alloprene were added in turn. A very viscous paste resulted, which was mixed mechanically. The paste was then rolled out between two sheets of siliconcoated paper to a thickness of approximately 1.5 mm and allowed to convert for 6 hours in an oven at 60"C. After cooling, the adhesive was in the form of a cohesive, extremely tacky sheet which could be cut to the desired size and shape. This adhesive is highly compatible with the human body. Indeed, we have never yet observed any adverse reaction to it, even in patients who are allergic to many conventional medical adhesives. Although I cannot say that this material will never cause allergy, it appears to be superior in this respect to most known adhesives. The adhesive projects some way beyond the disc 3 in order to assist in keeping the device in good contact with the abdominal wall. Another adhesive composition is as follows: Butyl benzyl phthalate 6 ml Polyethyl methacrylate 2 g Alloprene 20 2 g Colloidal silica 0.5 g The polyethyl methacrylate was the same as used in the first adhesive. The mixing and conversion procedure was as described. The disc was composed of an acrylic copolymer which was made as follows. 16 parts of the polyethyl methacrylate described above were mixed with 10 parts of a liquid mixture having the composition 2% N,N-dimethyl-p-toluidine; 30% ethylene glycol dimethacrylate (available from Rohn & Haas); and 68% of butyl phthalyl butyl glycollate. The resulting fluid slurry was immediately poured into a mould and cured for 15 minutes at 60"C to form a flexible, rubbery disc. The accelerator (N,N-dimethyl-ptoluidine) may be replaced by other suitable tertiary amines, but it is preferable to select this material with care to avoid allergy problems. WHAT I CLAIM IS:

1. An adhesive composition comprising a gelled mixture of: (i) a poly (C 1 álkyl) methacrylate, (ii) a physiologically compatible liquid plasticizer, (iii) an inert particulate filler, and (iv) a chlorinated rubber.

16. An adhesive composition according

to claim 15 wherein said medicament is selected from antibiotics, antiseptics, coal tar derivatives and anti-inflammatory compounds.

17. An adhesive composition according to claim 1 comprising polyethyl methacrylate, butyl phthalyl butyl glycollate as plasticizer, colloidal silica as filler, and a chlorinated polyisoprene.

18. An adhesive composition according to claim 1 substantially as illustrated herein.

19. A surgical product comprising an adhesive composition according to any one of the preceding claims.

20. A surgical product according to claim 19 in the form of adhesive surgical tape.

21. A surgical product according to claim 19 in the form of an adhesive dressing.

22. An adhesive element for securing the pouch of an ostomy appliance to the skin around the stoma of a patient comprising a flexible pad having an aperture through which said stoma can pass, a face of said pad bearing an adhesive composition according to any of claims 1-18.

23. An adhesive element according to claim 22 wherein said pad is in the form of a disc having a central aperture.

24. An adhesive element according to claim 22 or 23 wherein said pad is of plastics material.

25. An adhesive element according to any of claims 22-24 wherein the portion of the pad surrounding the aperture is relatively stiff while the peripheral portion is more flexible.

26. An adhesive element according to any of claims 22-25 wherein the aperture in the pad, on the face to be adhered to the patient, is surrounded by a layer of hydrophilic gum which swells on contact with water.

27. An adhesive element according to claim 26 wherein said gum is contained in a moat between two upstanding webs formed on the pad.

28. An adhesive element according to claim 26 or 27 wherein said gum is karaya gum.

29. An adhesive element according to any of claims 22-28 wherein the face of said pad opposing said face bearing said adhesive composition is formed integrally with an ostomy pouch.

30. An adhesive element according to any of claims 22-28 wherein the face of said pad opposing said face bearing said adhesive composition is attached to an ostomy pouch.

31. An adhesive element according to claim 30 wherein said ostomy pouch is attached to said pad by a contact adhesive.

32. An adhesive element according to any of claims 22-31 wherein said pad comprises means for attachment to a belt.

33. An adhesive element substantiallv as illustrated in the accompanying drawing.

34. A method of making the adhesive composition of any of claims 1-18 which comprises mixing the components of said composition and allowing the resultant paste to convert to a homogeneous gelled composition at an elevated temperature.

3. A method according to claim 34 wherein said elevated temperature is in the range 40-80 C.

36. A method according to claim 34 or 35 wherein said poly (C,.calkyl) methacrylate has a particle size in the range 50-400 mesh (British Standard Sieve).

37. A method according to any of claims 34-36 wherein said paste is allowed to convert to a homogeneous gelled composition in situ on a surface to be rendered adhesive.

38. A dispersion of the composition of any of claims 1-18 in an organic solvent which dissolves all components of said composition except the filler.