Title of Invention

A PROCESS FOR PREPARING MODIFIED BIOCOMPATIBLE SPONGE

Abstract

This invention relates to a process for preparing modified biocompatible sponge comprising in the steps of: a. preparing a solution of the polyvinyl alcohol of high-visco- sity; b. adding to the solution of the polyvinyl a surfactant such as herein described; c. mixing solution of PVA and surfactant with an acidic solution chitosan followed by frothing the mixture obtained; d. adding an aldehyde crosslinker such an acid catalyst to crosslink the PVA and the chitosan to obtain the biocompatible sponge.

Full Text

This invention relates to a process for preparing modified bio-compatible sponge. This invention further relates to modified biocompatib Le .sponge Tor unproved absorption of: tissue f lu i ds and y,u rg i rvi I rfvom; I nµ-l ion. During ophthalmic surgical procedures, it is common Lo use vast: quantities of inexpensive and high swelling material to absorb blood and fluids from the opera t ion s i to at; very short { ›‹M i ,ods of time - For the intended application, the materia1s used shouId also be non-toxic, non-irritating and lint-free - There should be no release of particulate contaminants or addi fives either. The cotton swabs or cellulosic material that .ire generaL Ly used are not entirely lint-fret and can hence 1.nterf ero w:i. 111 111e healing process. It is therefore desirable ho use a roam or sponge structure for this application. Sponges "have a I so been used extensively as reconstruction ma tpr La I s I.or si.i;ncl:u ra I support and void filling applications. A sponge of partly denatured gelatin (pelloam) is used as a haemostatic agent during surgery. This sponge has also been used as a seal for the oval window of thcli middle ear to improve T hearing loss. Another sponge which has been used I or the same purpose is made of col lagen. Col lagen Conges have been used as a. matrix for drug delivery and as a haemostatic agent. Rigid polyur ethane foams have been applied to ‹]›r the tics as a i;o place¬ment for wood in artificial limbs and as leasts for bones. f Lexi-ble polyurethane foams have been used for 'disposable appl icat i. ons as wound. dressings. Silicone sponges have been used tor the correction of retinal detachment and to maintain the separation a n d u 1 i g n m e n t of t he d e n t a 1 arch d u r i. n g h c "* a "! i n q of toll \ › a 1 n I - ‹ ^ correction. Polytetrafluoroethylene and high density polyethylene sponges have been used for maxillofacial reconstruction. Polyvinyl alcohol sponges have been used as segments of a r hi Ei~ cial heart valve r blood vessel replacement, hernia repai L; , filter for pulmonary post resection spaces, etc,. A polyvinyl alcohol sponge formed using formaldehyde as crbss-1inker has been used as an opthalmic sponge (1) due to high absorbency of water -900% w/w at 1 minute, high rate of swelling and good compatabi-lity with occular tissues• OBJECTS OF THE INVENTION An object of this invention is to propqse a sponge that is bio¬compatible and has very high absorpti^itv as well as rate of absorption towards blood, water and tissue fluids, and can be used as a swab for opthalmic applications or as an haemostat or as a wound dressing material for burns, surgical or other wounds, ulcers, etc„. Another object of this invention is to propose a sponge which can also be used as any wet absorbent article such as surgical sponge, disposable diaper, sanitary napkin, tampons or the like. Still another object of this invention is to propose a sponge that may be used for surgical reconstruction. A further object of this invention is to propose a process for the production of a biocompatible sponge with high absorptivity towards tissue fluids such as water, blood or other. According to this invention, there is provided a process for preparing modified biocompatible sponge comprising i n thr* stops of : preparing a solution of the polyvinyl alcohol of high visco¬sity; \or. adding to the solution of the poly vinyl alcohol a surfactant ••J such as herein described; ?c. mixing the solution of PVA and surfactant with an acidic solution of chitosan followed by frothing the mixture thus obtained; d• adding an aldehyde cross-linker such as herein described "and an acid catalyst to cross linker' the PVA and the chitosan to obtain the biocompatible sponge. DETAILED DESCRIPTION OF THE INVENTION The present invention also relates to polyvinyl acetal and poly¬aminosaccharide blend compositions, which can be l.ormuia Led in the form of foams or sponges. The natural polyaminosaccharide used in the examples of this invention is chitosan which is found abundantly in nature in crabshell, etc.. The invention is particularly useful for applications where a high absorption rate coupled with higher absorbency towards tissue fluids is desired. The invention includes the methods for making the compo¬sitions , materials and the sponge. The polyaminosaccharide used in this indention, namely chitosan was obtained from chitin by deacetylatipn using strong aqueous alkali. Chitin is a very abundant naturally occurring polysaccha-rides, consisting of B (1-4) 2 acetamido-^-^^oxy-D-glucose units. Chitosan has been used as an anti-thromnogcnio and hnomoc•ompnl: i -ble coating for artificial blood vessels Jand is acid-soluble. In this invention, a dispersion of a hiiahly acidic and viscous aqueous solution of polyvinyl alcohol (JPVA) with viscosity in the range of 500-800 cps is mixed with a‹ surfactant. The surfac¬tant used should have a dissociation constant of the order of -2 10 in highly acidic media. An acidic solution of the chitosan is dispersed in the solution of PVA and the mixture is frothed to its maximum extent by mechanically beating in air with a high speed stirrer. An aqueous solution of the cross linking agent when mixed with the above metioned dispersion is presented to the external surface of the foam bubble at a relatively higher cross linking density at the surface than in the interior. This phenomena causes the bubbles to be cross linked without conside¬rable collapse and leads to the formation of a sponge or foavn with uniformly small pores and proper phase mixing. While any * aldehyde that is capable of being dispersed in aqueous media is also capable of forming the sponge for greater phase mixing, it is desirable to use an aldehyde with a high reaction as glu- taraldehyde or formaldehyde, etc.. Glutaraldehyde is having the added advantage that it can crosslink the chitosan moieties also effectively resulting in a better1 phase mixing for the PVA-chitosan blend. The structure formed is ak i.n to ‹-m i nl ‹M pom-trating polymer network. In preparing the1sponges of this invention, the polyvinyl alcohol solution is prepared in a concentration of 5-2 0% by weight of PVA depending on the molecular weight used, so that the final solution viscosity is between 500-800 cps. The molecular weight of the PVA may hence vary from 10,000 to 1,25,000. For the typi¬cal medical application, the more hydrolysed grades of PVA are preferred for the invention to avoid solution formation in cold water. The aqueous acidic solution of chitosan is prepared in the range of 1-3% by weight in dilute acid. Volumes of the chito¬san solution to be added will vary with the actual desired compo¬sition. Examples of acids that may be used to dissolve the chito¬san are hydrochloric acid, acetic acid, etc.. In order to obtain the sponges of the high absorptivity as claimed in this invention, the surfactants used should bo capable of decreasing the surface tension of the solution in a strongly acidic media. Examples of such surfactants are sodium lauryl sulphate, polyoxyethylene sorbitnto, oho.. Tho rniu'pnl mI i on of the surfactants used are in the range of less than 2% by weight of polyvinyl alcohol in the case of polyoxyethylene sorbi-tate, whereas higher concentrations of around 20% are required in the case of sodium lauryl sulphate, for obtaining self-sus¬taining cross linked foams of minimum shrinkage. The PVA cross-linking reaction is acid catalysed. In the produc¬tion of self-sustaining foams, the typical concentrations of the concentrated acids (35% hydrochlori,c acid) used are upto 5% of the volume of the PVA solution. The foams hence produced in the invention are light and have least amount of shrinkage. The role of the cross linker is to crosjslink the froth in the form of a self-sustaining sponge before! the forces of aravitv and interlamellar forces of the liquid films cnuao l:ho 1 ".roth to col lapse. Use of higher concentrations of nlclohy‹los I;PSW 1 I: in ef f inient cross linking but can al so resu ! t i n Hio !' Characteristic examples of the composition of the different reactants used for the preparation of the!self-sustaining foams. WE CLAIM: 1. A process for preparing modified bio£ompatible sponge compri¬sing in the steps of : a• preparing a solution of the polyvin^l alcohol of high visco- sity ; ! bj adding to the solution of the poly vinyl a sur f nct:nn t such as herein described; ;"c. mixing the solution of PVA and surfactant with an acidic "Solution of chitosan followed by frothing the mixture thus obtained; d. adding an aldehyde crosslinker such as herein described and an acid catalyst to crosslink the PVA and the chitosan to obtain the biocompatible sponge. 2 • The process as claimed in claim 1 wherein the average molecu¬lar weight of the PVA used is in the range of 10,000 and 1,25,000. 3. The process as claimed in claim 1 wherein the solution of PVA in water has a concentration of 5-20% by weight of PVA. 4. The process as claimed in claim 1 wherein the viscosity of the PVA solution is in the range of 500-800 cps. 5. The process as claimed in claim 1 wherein the surfactant -2 has a siddociation constant of 10 in highly acidic media. 6. The process as claimed in claim 1 wherein the surfactant is selected from sodium lauryl sulphate, polyoxyethylene sorbi-tate, etc.. 7. The process as claimed in claim 1 wherein the concentration of surfactant used is in the range of less than 2% by weight of PVA in the case of polyoxyethylene sorbitate, upto about l 20% in the case of sodiumlauryl sulphate. 8. The process as claimed in claim 1 wherein the solution of chitosan is prepared in a concentraticbn of 1-3% by weight in a dilute acid. 9. The process as claimed in claim 8 wherein said acid is selec¬ ted from hydrochloric acidr acetic acid, etc.. 10. The process as claimed in claim 8 wherein a 0.01N hydrochlo¬ric acid is used as the dilute acid. 11. The process as claimed in claim 1 wherein frothing the PVA-chitosan solution is effected by mechanically beating in air with a high speed stirrer. 12. The process as claimed in claim 1 [wherein the proportion of PVA:Chitosan in the solution is in 'the range of 100:0 to 70:30 by weight. 13. The process as claimed in claim 1 whein said acid catalyst is a mineral acid such as hydrochloric acild. 14. The process as claimed in claim 131 wherein said acid is preferably 35% hydrochloric acid. 15. The process as claimed in claim I3l wherein the acid used is upto 5% of the volume of the PVA solution. 16. The process as claimed in claim 1 wherein said aldehyde crosslinker is selected from glutaraldehyde, formaldehydef etc. . 17. The process as claimed in claim 1 wherein the aldehyde cross- linker is glutaraldehyde. 18. The process as claimed in claim 1 wherein a crosslinker concentration is of upto 2 mg/dl. 19. A process for preparing modified biocompatibl c spon‹jo sub¬stantially as herein described and illustrated in the accompany¬ing examples.

Documents:

1296-mas-1997-abstract.pdf

1296-mas-1997-claims filed.pdf

1296-mas-1997-claims granted.pdf

1296-mas-1997-correspondnece-others.pdf

1296-mas-1997-correspondnece-po.pdf

1296-mas-1997-description(complete)filed.pdf

1296-mas-1997-description(complete)granted.pdf

1296-mas-1997-description(provisional).pdf

1296-mas-1997-form 1.pdf

1296-mas-1997-form 26.pdf

1296-mas-1997-form 4.pdf

1296-mas-1997-form 5.pdf