JPS6142755B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to medical devices and materials suitable therefor. More particularly, the present invention relates to adhesive compositions particularly useful for attaching medical devices to living animals.

To attach a medical brace or device,
It is necessary to adhesively bond to an animal living body, especially a human living body. Although many adhesive compositions are known to date, few are suitable for application to human skin. Adhesives of this type have strict requirements: they must bond strongly to human skin, but they must also be able to be removed without damaging the skin surface. Furthermore, it should not cause irritation even if it is worn for a long time.
Allergenicity should be extremely low. Also, it must not contain carcinogenic substances. The requirement to be non-allergenic is particularly difficult to meet, and the majority of adhesives currently on the market are prone to significant rates of allergy.
If a patient is prone to allergies, many adhesives may have to be tested before finding one that is compatible. This is a waste of time for the doctor, while the patient suffers from the allergic reaction.

According to one aspect of the invention, the invention comprises (i) a poly(lower alkyl) methacrylate, (ii) a physiologically compatible liquid plasticizer, (iii) an inert particulate excipient, and (iv) An adhesive composition comprising a gelled mixture of chlorinated rubber is provided.

The lower alkyl group of the poly(lower alkyl) methacrylate contains 1 to 4 carbon atoms, and the preferred polymer is polyethyl methacrylate. Poly(lower alkyl) methacrylates are brittle solids with molecular weights preferably between 50,000 and 1,000,000;
100,000-500,000, for example about 200,000, is particularly preferred.

The plasticizer component is a physiologically compatible liquid that serves to plasticize the poly(lower alkyl) methacrylate. A preferred group of plasticizers are ester plasticizers, especially esters of dicarboxylic acids. Although diesters of fatty acid dicarboxylic acids may also have suitable properties, diesters of aromatic dicarboxylic acids, especially diesters of phthalic acid, are preferred. The alcohol component of such phthalic acid diesters can be chosen, for example, from alkanols, alkoxycarbonyl-substituted alkanols and aralkanols. Alkanols have, for example, 1 to 8 carbon atoms and may be substituted with lower alkoxycarbonyl radicals. A plasticizer which is particularly satisfactory in all respects is butylphthalyl butyl glycolate. This compound is commercially available from Monsanto as "Santicizer B 16". Other phthalate diesters that can be used include butylbendiphthalate, also available as "Santicizer 160" from Monsanto.

Other groups of plasticizers that can be used in the present invention include:
There are N-substituted arylsulfonamides. Aryl groups include, for example, phenyl optionally substituted with lower alkyl, such as tolyl. The N-substitution rate is preferably lower alkyl. An example of a plasticizer of this type is N-ethyl-o,p-toluenesulfonamide. This is commercially available from Monsanto as "Santicizer 8".

Although the precise chemical nature of the plasticizer is not an issue in the present invention, it must be physically compatible with the other components of the composition and physiologically compatible. . It should be as non-allergenic as possible. Approval by the FDA for addition to food and pharmaceutical formulations indicates that the substance is physiologically compatible.

The inert particulate excipient serves to stabilize the composition in the form of a cohesive gel. Excipients also reduce the tackiness of the composition, so the proportion and nature of the excipients are selected to provide the desired tackiness. Without excipients, the adhesive is too strong to cause harm to human skin, but it is difficult to remove.
A preferred excipient is silica. The excipient preferably has a colloidal particle size. Other excipients may include pulverulent calcium carbonate, diatomaceous earth, silicates such as powdered glass, especially barium glass, lithium aluminum silicate or talc.

Chlorinated rubber improves the tack and cohesive properties of the composition. Preferred chlorinated rubbers are manufactured by Imperial Chemical
Highly chlorinated hydrocarbons such as highly chlorinated polyisoprene available as Alloprene 20 from Industries.

The proportions of each component in the composition are, for example, 16-84 g, preferably 20-45 g, of poly(lower alkyl) methacrylate and 6 g of excipient per 100 ml of plasticizer.
-16g, preferably 8-12g, and chlorinated rubber 16-
67g, preferably 20-40g. The relative ratio of each component is adjusted within this range so as to obtain desired properties. Optimal component ratios for a particular desired property combination can be determined by simple experimentation.

The composition of the present invention can be produced by dispersing powdered poly(lower alkyl) methacrylate in a plasticizer and dissolving this powder in the plasticizer in the form of a gel. The excipient and chlorinated rubber may be added at any stage, but it is preferable to add them when the viscosity is low and they can be mixed completely. A preferred mixing order is to first mix the excipient with the plasticizer, then add the poly(lower alkyl) methacrylate, and finally add the chlorinated rubber.

The mixture is initially a hard paste, but as the plasticizer dissolves the poly(lower alkyl) methacrylate, it turns into a homogeneous gel. This conversion occurs slowly at room temperature, but is accelerated by heating to, for example, 40-80°C. It can be used at high or low temperatures depending on convenience. At 60°C, conversion is usually complete in about 4 to 5 hours. The conversion time is primarily determined by the particle size of the poly(lower alkyl) methacrylate. Preferably, this material is a powder in the range 50-400 mesh (British standard), particularly less than 200 mesh.

At the end of the conversion, the composition becomes a clear, flexible gel with a rubbery consistency and tackiness to the touch. Shows good adhesion to human skin. The composition is stable, remains cohesive, exhibits no flowability even at high excipient concentrations, and retains tack and adhesive properties over long periods of storage and use.

Conveniently, the composition gels in situ on the surface to be adhered. The composition may also be spread over a release coated surface and gelled in a layer prior to conversion, and this layer then placed on the material to be made into an adhesive composition. Alternatively, the composition may be dispersed in an organic solvent such as chloroform or a chlorinated hydrocarbon such as methylene dichloride, which dissolves all components of the composition except for excipients, and the dispersed composition may be used as an adhesive composition. The solvent may be evaporated. Suitable solvents include lower aliphatic ketones such as acetone, aliphatic esters such as diethyl ether, and lower alkanols such as ethanol. Because some patients have allergic reactions to common organic solvents, it is often preferable to avoid their use. That is, it is preferred to roll the pasty composition into a thin layer between surfaces provided with a release coating and to apply this mixture onto the material for the adhesive composition, either before or after converting it into a gel.

The compositions of the present invention have wide application as adhesives, particularly, but not exclusively, for application to human skin. for example,
Can be used as an adhesive part of surgical tape and other medical and surgical bandages, covers and braces. Surgical tape or plaster is made by supporting the adhesive of the present invention on one surface of a flexible support. The support used is a textile or a plastic film, in particular a microporous plastic film. If a drug-containing plaster is desired, the drug can be added to the adhesive. For example, antibiotics, fungicides, coal tar derivatives (which are useful for certain skin diseases) and anti-inflammatory compounds such as steroids can be added. This type of plaster can be used to cover skin wounds or other injury sites, such as leg ulcers, such as varicose ulcers. In this case, the adhesive of the invention has the advantage that it exhibits no adhesive properties in its presence.
That is, when a bandage is used to cover a damaged or wet area of the skin, the bandage adheres only to the surrounding uninjured skin and does not adhere to the damaged area.

A particularly advantageous use of the invention is when used to secure a drainage collection bladder around a skin opening in a patient during a fistula placement procedure. After a fistula is placed in the ileum, colon, ureter, etc., an opening is left to drain waste products. Waste products are collected in sacs that are periodically converted. It has been quite difficult to secure this sac in a manner that is comfortable for the patient and does not leak.

As another aspect of the present invention, in an adhesive component for fixing a drainage fluid collection bag to the skin around the opening of a patient when a fistula is installed, a hole communicating with the opening is provided,
An adhesive component comprising a flexible pad having an adhesive composition of the present invention supported on its surface is provided. The other surfaces may be formed integrally with the wall of the bladder or may be attached by suitable mechanical means such as adhesives.

The pad, which is generally disc-shaped with a central hole, is preferably manufactured from a plastic material. Suitable plastic materials include plasticized acrylic polymers and plasticized vinyl polymers such as plasticized PVC. Since a portion of the pad will be in contact with the patient, the pad must be made of materials that will not induce undesirable reactions when in contact with human organisms. In particular, this material must be non-allergenic. Suitable plastic materials can be selected from those used in the dental field. The accelerators (such as tertiary amines, peroxides or quinones) used to cure the compositions forming the pads must be selected with particular care in this regard. Preferably, the composition is cured by actinic (ultraviolet or visible) radiation.

Preferably, the pad is relatively rigid around the hole, while the distal portion is more flexible. This configuration can be created by increasing the thickness of the pad toward the center or by placing one or more reinforcing webs around the hole. However, the pad must have sufficient overall flexibility so as not to cause discomfort to the patient and to conform closely to the curved surface of the abdominal wall.

In a particularly preferred embodiment, the surface of the pad hole that contacts the patient is surrounded by a hydrophilic rubber layer that swells when in contact with water. Preferably, it is contained in a groove between two upright webs formed on the pad. A preferred hydrophilic rubber is India rubber. When there is liquid seeping out of the openings, the Indian rubber absorbs moisture and swells. The swollen rubber provides a good seal against the abdominal wall and also effectively prevents fluid from leaking. This can also prevent the adhesive of the invention from coming into contact with moisture.

Instead of Indian rubber, other natural or synthetic swellable hydrophilic rubbers can also be used. For example, agar, alginate or a suitable grade of polyvinyl alcohol can be used.

The other side of the pad may be integrally formed with a drainage collection bladder during stoma installation, or the bladder may be attached by suitable mechanical means, such as clips, or more preferably by adhesive. Since this side of the pad does not contact the skin, any suitable adhesive can be used. Although the adhesive need not be physiologically compatible, the adhesives of the invention are often highly suitable for this purpose as well.

Although the adhesive of the present invention in the form of a cohesive sheet can be applied from the end of the pad to the top of the adhesive sheet and used to secure the bladder to the pad, it may not be used for this purpose. Ba,
It is preferable that the top surface or edges of the adhesive sheet not be adhesive so as not to adhere to clothing or the like.

According to a preferred embodiment, the sac or pouch that collects the discharge from the opening can be replaced without removing the pad from the patient. This avoids having to remove the entire brace from the patient every day. This embodiment is particularly applicable to the case of an ileostomy installation device. In this embodiment, the bladder is preferably secured to the pad by adhesive.

The appliance described above is particularly useful for fistula patients, but is also effective in collecting fistula drainage. If desired, the pad can be provided with means for attaching it to the belt. For example, holes or protrusions may be provided at each end of the pad (or diametrical ends if the pad is circular) for connection to corresponding fastening means at each end of the belt.

One aspect of the invention will be illustrated with reference to the drawings.
The drawing shows a cross-sectional view of the adhesive component of the invention. That is, an opening 2 is provided in the patient's abdominal wall 1 by surgery. The adhesive part of the invention is a disk 3 made of plastic material with a hole 4 in the center. Hole 4 has concentric webs 5 and 6
An india rubber ring 7 is placed in a groove formed within the groove. The outside of the disc is adhered to the abdominal wall by a sheet 8 of adhesive having the following composition; the opposite side 9 of the disc is used for attachment with a sac or pouch for collecting exudates.

The composition of the adhesive is as follows. Parts correspond to ml and g for liquids and solids, respectively.

Butylphthalyl butyl glycolate 6 parts Polyethyl methacrylate 2 parts Alloprene 20 2 parts Colloidal silica 0.65 parts Butylphthalyl butyl glycolate
It is commercially available as Santicizer B16 from Monsanto, but can also be produced by conventional esterification methods.

Polyethyl methacrylate is a powder below 240 mesh (British Standard) and has an average molecular weight of approximately 200,000. ADI Plastics Limited, Marton;
Obtained from Blackpool, England.

Alloprene 20 is manufactured by Imperial Chemical
Industries (Alloprene Section), Runcorn;
Obtained from Cheshire, England.

Silica is of medicinal use with low iron content.

The silica is first mixed with butylphthalyl butyl glycolate and polyethyl methacrylate and alloprene are added sequentially. Mix mechanically as a very viscous paste is obtained. The paste is then rolled between two sheets of silicone-coated paper to a thickness of approximately 1.5 mm and allowed to convert in an oven at 60° C. for 6 hours.

After cooling, the adhesive is obtained as a cohesive, highly tacky dosage form that can be cut into the desired size and shape. This adhesive has high compatibility with human organisms. Even patients who are allergic to many commercially available medical adhesives have not been observed to develop any side effects to this adhesive. Although it cannot be said that this material will never cause allergies, it appears to be superior to most known adhesives in this respect. To ensure complete adhesion of the appliance to the abdominal wall, the adhesive should protrude somewhat outside the disc 3.

Examples of other adhesive compositions are shown below.

Butyl benzyl phthalate 6 ml Polyethyl methacrylate 2 g Alloprene 20 2 g Colloidal silica 0.5 g The polyethyl methacrylate is the same as that used in the first adhesive. Mixing and conversion operations are as described above.

The disc is made of acrylic copolymer and is manufactured by the following method. A liquid mixture 10 containing 16 parts of the polyethyl methacrylate described above having a composition of 2% N,N-dimethyl-p-toluidine, 30% ethylene glycol dimethacrylate (Rohn & Haas) and 68% butylphthalyl butyl glycol.
Mix with parts.

Immediately pour the obtained fluid slurry into a mold and pour it into a mold for 15 minutes.
Cure at 60°C for minutes to form a flexible rubber-like disc. Other suitable tertiary amines may be used in place of the promoter N,N-dimethyl-p-toluidine, but this material is preferred to avoid allergy problems.

The adhesive composition of the present invention and its manufacturing method are as described in the claims, but as described above, the composition can be advantageous in various aspects. Next, an embodiment thereof will be shown.

(1) A composition in which the adhesive composition further contains a medicine.

(2) The composition according to item (1) above, wherein the medicament is selected from antiseptics, bactericides, coal tar derivatives, and anti-inflammatory agents.

(3) A medical fitting containing the adhesive composition.

(4) The fitting device according to item (3) above, wherein the adhesive device is in the form of adhesive surgical tape.

(5) The fitting according to item (3) above, wherein the fitting is in the form of an adhesive plaster.

(6) An adhesive member for fixing a waste collection bag to the skin around the patient's opening during fistula placement,
An adhesive member comprising a flexible pad having a hole communicating with the opening and supporting the adhesive composition of the present invention on the surface.

(7) The adhesive member according to item (6) above, wherein the pad is disc-shaped with a hole in the center.

(8) The adhesive member according to item (6) above, wherein the pad is made of plastic.

(9) The adhesive member according to item (7) above, wherein the portion surrounding the hole of the pad is relatively strong, and the surrounding portion is flexible.

(10) The surface of the hole in the pad that adheres to the patient's skin is surrounded by a hydrophilic rubber layer that adheres to water and swells, according to any one of items (6) to (9) above. Adhesive member.

(11) The adhesive member according to item (10) above, wherein the rubber is contained in a groove between upright webs formed on the pad.

(12) The adhesive member according to item (10) above, wherein the rubber is Indian rubber.

(13) The adhesive member according to item (6) above, wherein the surface of the pad opposite to the adhesive composition supporting surface is integrally molded with the waste collection bag.

(14) The above, wherein the surface of the pad opposite to the adhesive composition supporting surface is adhered to the excrement collection bag.
The adhesive member described in (6).

(15) The adhesive member according to item (14) above, wherein the pad and the waste collection bag are bonded together using a pressure-sensitive adhesive.

(16) The adhesive member according to item (6) above, wherein the pad has means for attaching it to a belt.

(17) A dispersion of the adhesive composition of the present invention in an organic solvent, in which all components of the composition except excipients are dissolved.

[Brief explanation of the drawing]

The figure is a cross-sectional view showing an example of the adhesive component of the present invention in use, in which 1 is the patient's abdominal wall, 2 is a drainage collection bag provided in the opening, 3 is a disc-shaped support, and 4 is the The holes provided, 5 and 6 are webs provided concentrically with the edges of the holes, 7 is a ring of india rubber added to the groove between the webs, and 8 is a sheet of adhesive.

Claims (1)

[Claims] 1 (i) poly(lower alkyl) methacrylate,
An adhesive composition comprising a gelling mixture of (ii) a physiologically compatible liquid plasticizer, (iii) an inert particulate excipient, and (iv) a chlorinated rubber. 2. The adhesive composition according to claim 1, wherein the poly(lower alkyl) methacrylate is polyethyl methacrylate. 3. The adhesive composition according to claim 1 or 2, wherein the poly(lower alkyl) methacrylate has a molecular weight of 50,000 to 1,000,000. 4. The adhesive composition according to claim 3, wherein the poly(lower alkyl) methacrylate has a molecular weight of 100,000 to 500,000. 5. The adhesive composition according to any one of claims 1 to 4, wherein the plasticizer is a phthalic acid diester. 6 an alkanol in which the alcohol component of the phthalic acid diester has 1 to 8 carbon atoms optionally substituted with an alkoxycarbonyl residue;
The adhesive composition according to claim 5, which is selected from alkanols. 7. The adhesive composition according to claim 5, wherein the plasticizer is butylphthalyl butyl glycolate. 8. The adhesive composition according to claim 5, wherein the plasticizer is butylbenzyl phthalate. 9. The adhesive composition according to any one of claims 1 to 4, wherein the plasticizer is an N-(lower alkyl)arylsulfonamide. 10. The adhesive composition according to claim 9, wherein the plasticizer is N-ethyl-o,p-toluenesulfonamide. 11. The adhesive composition according to any one of claims 1 to 10, wherein the inert particulate excipient is colloidal silica. 12. Any one of claims 1 to 11, wherein the chlorinated rubber is highly chlorinated polyisoprene.
The adhesive composition described in . 13 For 100 ml of plasticizer, 16-84 g of poly(lower alkyl) methacrylate, 6-16 g of excipient
The adhesive composition according to any one of claims 1 to 12, containing 16 to 67 g of chlorinated rubber. 14 For 100 ml of plasticizer, 20-45 g of poly(lower alkyl) methacrylate, 8-
12 g, and 20-40 g of chlorinated rubber. 15. The adhesive composition according to claim 1, comprising polyethyl methacrylate, butylphthalyl butyl glycolate as a plasticizer, colloidal silica as an excipient, and polyisoprene chloride. 16 Adhesive composition consisting of a gelling mixture of (i) poly(lower alkyl) methacrylate, (ii) a physiologically compatible liquid plasticizer, (iii) an inert particulate excipient, and (iv) a chlorinated rubber. A method for producing an adhesive composition, the method comprising mixing the constituent components of the composition to form a paste, and heating the resulting paste to convert it into a homogeneous gelled composition. Method. 17. The manufacturing method according to claim 16, wherein the heating is performed at a temperature in the range of 40-80°C. 18. The manufacturing method according to claim 16 or 17, wherein the poly(lower alkyl) methacrylate has a particle size in the range of 50-400 mesh (British standard). 19. Claim 16, wherein the homogeneous composition of the paste is carried out in situ on the surface to be bonded.
The manufacturing method according to any one of Items 1 to 18.