Medical adhesive

Details Medical adhesive Medical adhesive

1999-04-22

2001-03-13

Williamson, Michael A. (Department: 1616)

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Web, sheet or filament bases; compositions of bandages; or...

C424S443000, C424S444000

Reexamination Certificate

active

06200595

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a medical adhesive which comprises a polyion complex film formed from a polycationic substance and a polyanionic substance. The medical adhesive of the present invention, which is in the form of film, absorbs blood or exudate from living tissues at the affected part and sticks to the tissue surface as it gels. It is particularly suitable for use as a tissue adhesive for surgical operations.
2. Discussion of the Background
Conventional tissue adhesives for surgical operations are illustrated below.
A typical one is so-called fibrin glue composed of fibrinogen, blood coagulation factor XIII, and thrombin. It is commercially available from several producers. Containing fibrinogen derived from human plasma, it has a disadvantage of being possibly infected with pathogenic organisms. In addition, it necessitates a step of mixing several materials immediately before use. This is troublesome.
Another one is cyanoacrylate-based tissue adhesive, which is also commercially available. It cures fast and provides high bond strength, but it has a disadvantage of evolving harmful formaldehyde upon decomposition in the living body.
A new product in the Japanese market is a tissue adhesive composed of gelatin, resorcinol, and formaldehyde. It also poses a problem with toxicity due to formaldehyde. In addition, it necessitates a step of mixing several reagents immediately before use. This is troublesome.
A tissue adhesive based on diisocyanate-urethane prepolymer is disclosed in Japanese Patent Laid-open No. 290465/1985, U.S. Pat. No. 4740534, and U.S. Pat. No. 4806614. It has not yet been put to practical use because it evolves, upon decomposition, diisocyanate which may be carcinogenic.
Conventional tissue adhesives shown above have many problems with biological safety (e.g., infection, sensitization, and toxicity) and handling properties.
In the meantime, it is well known that a polyion complex is formed rapidly when a polycationic substance and a polyanionic substance are mixed together in the presence of water. The polyion complex finds use in many application areas including drugs and medical instruments. An example of it is a polymeric composite material obtained by reaction between an anionic partial substitution product of dextran and a cationic partial substitution product of polysaccharide, which is used as a hemostatic in the form of powder, granules, or tablets, as disclosed in Japanese Patent Laid-open No. 110693/1978. Another example is aqueous solutions of polyanionic material and polycationic material (containing a calcium salt solution) which form a wound protecting layer when sprayed together on a wound, as disclosed in Japanese Patent Laid-open No. 73665/1986. The above-mentioned conventional polyion complex is applied in the form of powder or formed in situ on the wound from two solutions mixed together. On gelation, it merely gives rise to a gel which is not strong enough to be used as a tissue adhesive.
Another application of the polyion complex is in the active ingredient of an agent to promote regeneration of periodontal tissues by injection into periodontal pockets, as disclosed in Japanese Patent Laid-open No. 287538/1991. However, nothing is disclosed about use as a tissue adhesive.
A multilayered body for wound treatment is disclosed in Japanese Patent Laid-open No. 224293/1996. It is composed of chitosan, alginic acid, and chitin which arc arranged one over another on a substrate. It is produced by coating the substrate with chitin (or chitin dispersion) and then with a previously prepared chitosan-alginic acid complex, and finally drying the thus formed laminate. Since chitosan and alginic acid are not dissolved in water when they are made into a complex, they do not form a polyion complex in the multilayer body for wound treatment.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a medical adhesive which, after application to an affected part, absorbs blood or tissue exudate from the affected part, thereby turning into a gel which sticks to the affected part and firmly bonds tissues together.
It is another object of the present invention to provide an easy-to-use medical adhesive which dispenses with such pretreatment as mixing and dissolution during operations.
It is further another object of the present invention to provide a medical adhesive which is safe for the living body without possibility of infection and sensitization.
After their intensive studies, the present inventors found that the above-mentioned objects are achieved by a medical adhesive which comprises a polyion complex film formed from a polycationic substance and a polyanionic substance. The present invention was completed on the basis of this finding.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The polycationic substance used in the present invention is not specifically restricted so long as it meets the requirement that it have a plurality of cationic groups in the molecule so as to form a gel-like polyion complex with the polyanionic substance (explained later) in the presence of water, with the polyion complex functioning as an adhesive for living tissues, causing little harmful reaction to the living body. It should preferably be one which is decomposed and absorbed by the living body after the affected part has healed.
Another condition for the polycationic substance is that it have sufficient hydrophilic groups to dissolve or swell in water and be positively charged in water due to its cationic groups formed by dissociation.
Examples of the cationic group include amino group, monoalkylamino groups (such as methylamino group, and ethylamino group), dialykylamino groups (such as dimethylamino group and diethylamino-group), imino groups, and guanidino groups. The polycationic substance should preferably contain more than one amino group in its molecule.
Any known polycationic substance may be used in the present invention. Preferred examples include basic polysaccharides (such as chitosan and aminated cellulose), homopolymers or co-polymers of basic amino acids (such as polylysine, polyarginine, and lysine-arginine copolymer), basic vinyl polymers (such as polyvinylamine and polyallylamine), and their salts (such as hydrochloride and acetate). Of these examples, basic polysaccharides and their derivatives (such as acetylated products) and salts are particularly preferable. A preferred example of the basic polysaccharides is chitosan. Chitosan is a deacetylation product of chitin. For chitosan to have good water solubility and an ability to be absorbed by the living body, its degree of deacetylation should be in the range of 40-100%, preferably 45-90%, more preferably 50-80%.
The polycationic substance may be used in its crosslinked form. If it has amino groups, it may be crosslinked by condensation of the amino groups with a dicarboxylic acid. Any other known methods may be used for crosslinking.
The polycationic substance is not specifically restricted in molecular weight. However, it should have a molecular weight such that its 1% aqueous solution at 20° C. has a viscosity of 10,000 cp or lower, preferably 5,000 cp or lower. This viscosity increases accordingly as the molecular weight increases. With a higher viscosity, the solution is difficult to cast into film, and the resulting film becomes hard when dried and is poor in ability to be absorbed by the living body.
The polycationic substance that can be used in the invention may be a low-molecular weight diamine or polyamine. They include, for example, diaminoalkanes having 2 amino groups in one molecule (such as diaminoethane, diaminopropane, diaminobutane, diaminopentane, and diaminohexane), mono- or dilysylaminoalkanes having 3-4 amino groups in one molecule (such as N-(lysyl)-diaminoethane, N,N′-(dilysyl)-diaminoethane, N-(lysyl)-diaminohexane, and N,N′-(dilysyl)-diaminohexane), and those compounds having 5 or more amino groups in one molecule.
More than one kind of polycationic substance may be used f

Affiliated with

Also associated with

Rating

Medical adhesive does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Medical adhesive, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Medical adhesive will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2462804