Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1986-01-23
1989-12-12
Griffin, Ronald W.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514 54, 514 59, 514 60, 514 62, 536 551, 536 552, 536 56, 536 58, 536106, 536112, A61K 3170, C07H 300
Patent
active
048867870
DESCRIPTION:
BRIEF SUMMARY
This invention is concerned with a method of preventing adhesions or accretions of body tissues inter se with the aid of a degradable gel of a crosslinked polysaccharide containing carboxyl groups. The invention also comprises a gel product which is suited to this purpose, and a process for producing that gel product.
In many instances of practical surgery, it is highly desirable to have a simple means and method for preventing direct contact between tissues and for maintaining this contact-inhibiting effect also during a postoperative period the length of which will vary according to the actual type of surgery involved. Examples of such surgical procedures are manifold, spanning over a wide field: E.g. operations performed in abdominal regions where it is important to prevent adhesions of the intestine or the mesentery with concomitant gastrointestinal disorders; operations performed in the urogenital apparatus where it is important to ward off adverse effects on the ureter and bladder, and on the functioning of the oviduct and uterus; and nerve surgery operations where it is important to minimize the development of granulation tissue. When tendons are operated on there is generally a tendency towards adhesion between the tendon and the surrounding sheath or other surrounding tissue during the immobilization period following the operation. Essentially unsuccessful attempts have been made to solve this problem by using various kinds of sutures and by means of passive movements of the tendon during the healing process. In ophthalmological surgery it is often desirable to have degradable implants at one' s disposal which are to be applied in the angle of the anterior chamber of the eye for the purpose of preventing synechiae between the cornea and the iris; this applies especially in cases of reconstructions after severe damaging events. Moreover degradable or permanent implants are often desirable means for preventing adhesion in e.g. glaucoma surgery contexts (preventing adhesion in the subconjunctival filtration space) and in strabismus surgery.
Tubular implants may be employed for obtaining an improved flow from the anterior chamber, for thwarting obstruction of the lachrymal duct, and for improving the result of dacryocystorhinostomy.
In one particular type of articular surgery described by Engkvist et al. in Scand. J. Plast. Reconstr Surg. 14 (1980), 71-87, silicone plates Silastic 1/2 (Dow Corning) are introduced surgically in order to prevent accretions of cartilaginous tissue. After some 12 to 16 weeks, however, it is necessary to again remove the implant surgically. Thus, the techniques presently available necessitate removal of the inserted material after a suitable period of time in all cases where this material has to be of a rigid type for the sake of securing a high degree of mechanical stability. In other cases, where mechanical stability is not a major factor, it has been customary to use non-crosslinked dextran or hyaluronic acid. But even if a substance of such high viscosity as hyaluronic acid is used for application to contact surfaces the protection period thus obtained is too short to be satisfactory.
What is needed is therefore a product which is applicable in a suitable form for preventing adhesions and accretions between tissues and which optionally is to have the property of being degradable after a desired period of time.
We have now found that a gel of a crosslinked carboxyl-containing polysaccharide is exceedingly suitable for being used as a degradable implant.
The present invention is thus concerned with a novel degradable gel consisting of a polysaccharide which contains carboxyl groups--such as for example carboxymethyl starch, carboxymethyl dextran, carboxymethyl cellulose and glucosaminoglycans such as e.g. heparin, heparan sulfate, chondroitin sulfate and hyaluronic acid--and which has been crosslinked with a di- or polyfunctional epoxide. Examples of such epoxides are 1, 4-butanediol diglycidyl ether (BDDE), 1, 2-ethanediol diglycidyl ether (EDDE), 1-(2, 3-epoxypropyl)-2
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de Belder Anthony N.
Malson Thomas
Griffin Ronald W.
Peselev Elli
Pharmacia AB
Philpitt Fred
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