Title of Invention

A PROCESS FOR THE PREPARATION OF A BIOCOMPATIBLE SPONGE

Abstract

ABSTRACT "A PROCESS FOR THE PREPARATION OF A BIOCOMPATIBLE SPONGE" The invention relates to a process for the preparation of a biocompatible sponge comprising the steps of: mixing an aqueous polyvinyl alcohol solution with a surfactant to form a dispersion; crosslinking said dispersion in an acidic medium containing an aldehyde and a plasticizer to form a polymeric composition? curing said composition to form a sponge.

Full Text

This Invention relates to a biocompatible sponge and to a composition used for the production of said sponge,, During surgical procedures, vast quantities of inexpensive high swelling material are required to absorb blood and fluids from an ope r a t i on s i t e » Co 11 on sw ab s or o th e r c e 1 1 ulosic m ate r i al ar e generally preferred for this purpose» In opthalmic siurgery and with particular reference to cataract surgery, high swelling sponges are required to absorb the blood and fluids from the operation site in short period of less than 2 minutes. The sponges empjlcjyed for such applications should be non toxic, non irratatlng, lint free, sterile and non leach out any piarticuiar- matter. Sptonges are preferred as thin pointed strips to get good access to the delicate inner regions of the eye area. The sponges also should remain intract and not fray or fracture during surg i. c a 1 man i pu 1 at i ons. It is known tc-> use cotton buds, but which is attended with the disadvantages that such buds leave behind fibres in the operated area which is undesi rssb 1 e . It is also known to use non woven cellulose sponges. As irrever¬sible sweeling reduction or hornification resulting from drying of cellulose is well known, this could lead to fraying of the sponge on being manipulated freely and extensively by the BurQeon „ Other- d i s ad v an t ages of c e 11 u 1 osi c mat er i a 1 i s th at the cellulose can be of any origin The PVA il^onge is biocompatible and has foeen used as s surgical implant. Varying rts'sult's with this material have been reported, when used as s patch graft or for valve repair. The material has been reported to chan indicate extensive reac¬tion of the sponge in the short term consisting of acute inflsm--mation, and in the long term mature fibrouss tissue with a variable amount of caic H" ication, However, Cobey Accordingly, a primary object of this invention is to propose a biocompatible spcsnge 'for absorbing tissue fluids and which obviates the disadvantages associated with those of the prior art „ Another object of this invention is to propose a biocompatible sponge for absorbing tissue fluids which is inexpensive, highly absorbing and non to>:i*--« Still another object of this invention is to propose a biocom pstible sponge for absorbing tissue fluids, said sponge capable cj f b e i n g s t e r i 1 i s e d . Yet another- object of this invention is to propose a taiocom-patitale sponge for absorbing tissue fluids which does not fray or leave any lint in the operst ion site. A further object of this invention is to propose a composition for the prepa?-ation of s biocompatible sponge. A still further object of this invention is to propose a process for the production of s biocompatible sponge for abscjrbing tissue fluids. Further objects and advantages of this invention will be more apparent from the ensuing description. According to this invention, there is provided s polymeric compo¬sition for producing a bioco0>patibl e sponge for absjorbing tiE>sue fluids comprising s polymer such as polyvinyl alcohol crosslinked by an aldehyde in acidic conditions* in presence of a plastlcizer and sur f ac t an t» Further according to this invention, there is provided a process for the preparation of a biocompatible sponge comprising in the steps of s i, mixing an aqueous polyvinyl alcohol solution with a surfactant t o f o rm a d i sp e r s i on 5 ii, crcjssl ink ing said dispersion in an acidic medium containing an a 1d ehyde to f o rm a p o1yme r i c c ompos i t i on; iii. curing said composition to form a sponge. In accordance with this invention, an aqueous polyvinyl alcohol solution is first intimately mixed with an aqueous surfactant B.nd t h e n c r o s s 1 i n k e d i n a h i g h 1 y acidic (n e d i u m. The resultincj dispersion comprises of a highly acidic aqueous solution of polyvinyl alcohol, intimately mixed with a surfsctant, When an aldehyde crosslinking agent is introduced into the dispersion, prefersbly as an aqueous solution at suffi--ciently large quantities, the crosslinking agent is presented initially to the external surface of the foam bubbles, thereby cresting a relatively higher crosslinking density at the surface of the bubbles than in the interior. This causes the bubbles to be crosslinked without considerable collapse and leads to the formation of s sponge or foam with uniformly small pores. Any suitable aldehyde capable of being dispersed in aqueouss polyvinyl alcohol solution capable of formincj the sponge is employed. Suitable aldehydes ar-B by way of example formaldehyde, a c e t a 1 d e h y d e , b u t y r^ a 1 d e h y d e g 1 u t a r a 1 d e h y d e , e t c , . Further other macromol ecul es;. may be incorporated into the p>oly-" vinyl alcohol solution, even if they do not participate in the cross!inking reaction. These may be added to the polyvinyl alcohol in the aqueous phase, in concentrations ranging from 0.1 to 50*^ by weight, or more and become entrapped during the cross--linking process. Such added macromolecules include, for example polyethylene glycol, cartaoxymethyl dextran, carboxymethy1-cellulose, cellulose, starch, dextran, glycerol. The polyvinyl alcohol solution may be prepared by adding poly¬vinyl alcohol to water, stirring continuously to avoid the formation of lumps. The polyvinyl alcohol to be used is prefe¬rably of the fully hydrolysed grades, and can be of any molecular weight in the range 10,000 to 2,50,000. The temperature of the o aqueous phase can be any temperature from 25 C„ The polyvinyl alcohol solution produced is generally s viscous solution. The concentration of the polyvinyl alcohol varies between 5 to 2.0% depending on the molecular weight of the F'VA used to produce the desired viscosity. The surfactants are next added and should be capable of forming froth in a highly acidic media. Typical of such surfactants are sodium 1 aurylsulphate, tween, etc. and mixtures thereof, Ccjncen-tr-ation of the surfactant varies from 2% to 20% by weight. The acids used ss catalysts should preferably be strong acids capable of forming highly acidic media without undue dilution of the viscosity of the media. Examples of such acids are sulfuric acid, h y d roc h 1 o r i c a c i d a n d m i >; t u r e s t h e r e o f uj i t h a c on c e n t r a t i on of 10 to 30% by volume. The invention further includes s method for producing a foam or sponge. The method comprising first preparing the sponge by crosslinking the polyvinyl alcohol in acidic media using the suitable concentrations of the aldehyde in pcjlyethyl ene molds of suitable sizes. The sponge is cleaned in war-m tap water and methanol. The sponge is then dried and cut into desired shapess which may be parallelograms or spear shape or any other shape for medical applications. The cut sponges are then cleaned with distilled water using an Ultrasonicator till no particulate matter is observed in the extracted water when observed through a microscope. The sponge is then squeezed dry and allowed to swell in 2 to 20f4 aqueous solution of polyethylene glycol cjr other glycols with molecular weights ranging from 400 to 1000 until equilibrium absor^ption is attained. The swollen sponges may be 'dried at room tefnperature and used SB such, although more absorp¬tion may be obtained by dring in compressed conditions. Further objecrbs and advantages of this invention will be more apparent from the ensuing examples, which are not intended to imply any limitation on the scope of the invention. EXAMPLE 1 Preparation of formaldehyde crossiinked polyvinyl alcohol sponge, A solution of polyvinyl alcohol jurepared by dissolving polyvinyl alcohol in water using a high speed stirrer at a temperature of o o 25 C to £10 C so that the final concentration of polymer is 10y^ by weight. 3»5Q surfactant (sodium Isurylsulphate) was added tcs the poly¬vinyl alcohol solution with stirring st rotation control 800 to 2000 rpm, 50*'! to obtain good froth. The miKture is made strongly acidic by adding a mixture of 99^* sulphuric acid and 3&/i hydro- i chloric acid. Approximately 15ml of glycerol is next added to the mixture with stirring. 37% aqueous solution of formaldehyde entire rtiixture poured into polyethylene molds and allowed to cure. Curing period can be varied from 2 to 10 hrs.. Cleaning of the sponge The sponge is removed from the mold and washed with warm tap water till excess acid formaldehyde and surfactant are completely removed. Complete surfactant removal is checked by reaction of extract with barium chloride solution, till no precipitate of barium sulfate is observed. Cleamed sponge :i.s further cleaned with 50% methanol for one cycle. The sponge is then dried and cut into desired shape before extracting with distilled water„ Distilled water extraction is carried out using an ultrasonicator till no particulate mstter or fibres are seen in the water with the help of a microscope or a particle size analyser. The sponge is then squeezed dry and allowed to swell in 2-40% polyethylene glycol with molecular weight ranging from 400-1000 till equilibrium absorption is obtained. / where W ~ Weight of sponge in swollen state Wo = Original dry weight The sponge is dried by compressing between clean glass plates. The dried sf: polymer handles by biomedical grade cyanoacrylate glue. The final dry sponges are packed and sterilised by ethylene oxide s t e ?" i 1 i s a t i on . Pore size obtained 0.05 to 500 nucrons We 11 ability at 1 minute = 9005i E Saline extract and cotton seed oil extract of the sponge has passed the eye irratation test protocol. WE CLAIM: i- A process for the preparation of a biocompatible sponge comprising in the steps of: i. mixing an aqueous polyvinyl alcohol solution with a surfactant to form a dispersion; ii. crosslinking said dispersion in an acidic medium containing an aldehyde and a plasticizer to form a polymeric composition; iii. curing said composition to form a sponge. 2. A process as claimed in claim i wherein said plasticizer is glycerol. 3. A process as claimed in claim 1 wherein polyvinyl alcohol solution is stirred in order to avoid formation of lumps. 4. A process as claimed in claim 1 wherein said polyvinyl alcohol has molecular weight in the range of 10,000 to 2,50,000. 5. A process as claimed in claim 1 wherein said alcohol o o solution is heated to a temperature of 25 C to 100 C. 6. A process as claimed in claim i wherein said surfactant is, for example, sodium laurylsulphate. 7. A process as claimed in claim 1 wherein the concentration of said surfactant is 5 to 50% by weight of polyvinyl alcohol. 8. A process as claimed in claim 1 wherein said aldehyde is selected from formaldehyde, acetaldehyde, butyraldehyde, glutaraldehyde, and is present in a volume ratio of 1:2 to 6 with respect to polyvinyl alcohol. 9. A process as claimed in claim 1 wherein said sponge is cleaned in water and methanol. 10. A process as claimed in clain i wherein said cleaned sponge is cut into desired shapes, the cut sponge being further subjected to the step of cleansing for removal of particulate matter, squeezing the sponge and allowing it to swell in a swelling agent such as herein described, drying the swollen sponges. 11. A process as claimed in claim 10 wherein said swelling agent comprises 2 to 40% aqueous solution of glycol, such as polyethylene glycol. 12. A process for the preparation of biocompatible sponge substantially as herein described.

Documents:

2099-mas-1996 abstract.pdf

2099-mas-1996 claims duplicate.pdf

2099-mas-1996 claims.pdf

2099-mas-1996 correspondence others.pdf

2099-mas-1996 correspondence po.pdf

2099-mas-1996 description (complete) duplicate.pdf

2099-mas-1996 description (complete).pdf

2099-mas-1996 form-1.pdf

2099-mas-1996 form-26.pdf

2099-mas-1996 form-4.pdf

2099-mas-1996 petition.pdf