This invention relates to collagen products. In a particular aspect this invention relat to col lagen products made from solubl e col l agen. A n method by which soluble col lagen can be formed in quasi- crystal line structures by preci itation usi soluble polymers is described. The use of an aggrega of this quasi- crystal line col lagen to form a variety col l agen material s which have improved properti compared with existing col lagenous materials descr ibed. Such impro v ed co l l agen ma teria l s ha v appl ication in various fields including the manufactur for example, of products for medical use. Col lagen is an extremely common protein in th anima l kingdom and therefore many uses for product based upon collagen have developed. Many products u col lagen in either its nativ e form (i.e. the tripl helical structure pre-existing in an anima l or huma body), or regenerated into this form, or after denaturatio of the collagen, in the form of gelatine. Native collage is used for various products such as in the productio of leather from animal s ins, or such as the productio of sausage casings in which the col l agen is finel divided and reformed into the desired structure. There are also many uses of col lagen and for item made from col lagen in medical fiel ds such as i artificial arteries, veins, tendons, corneas, hear val ves, skin, or patches or the like which are used a replacement parts for disease or injury affected parts i humans, or in cosmetic applications such as mammar prostheses or injectable collagen, or in collage sponges, sutures or hae ostat materials which may b used during surgery or in the treatment of diseas (Chvapil, 1979). Many of these medical products made fro col lagen are at present unsatisfactory because of a inability to reproduce the native structure, compositio or strength which ex ists in the norma col lagenous tissue or because of the immune respons

el icited by the presence of immunogenic co l l agen or components or other material foreign to the body. In its native form in the body , col lagen exists in many types and in the most common of these types, col l agen e xi sts a s f ibr i l s i n which indi v i du a l co l l a g en mo l ecu l e s are arran ged in a s ta gger ed o v er l ap structure (Bornstein and Traub, 1979). These fibrils a re s t a bi l i s e d a n d m a d e i n s o l u b l e b y i n e r o 1 e c u 1 a r cross links between the non-helical portions (telopeptides) of adjacent collagen molecules (Bornstein and Traub, 1979). If the collagen from normal, mature tissue is to be made soluble the crosslinks must be broken, for example by digestion with an enzyme such as pepsin. Soluble col lagen can be reconstituted in a variety of ordered aggregate forms. Some are fibrous in form, and fibri l s in which the col lagen is arranged in its native staggered way can be reformed. The rate of th fibril reforming process is enhanced if col lagen with intact telopeptides is used. However, results from th use of in ectable soluble col lagen have shown that th telopeptides lead to an antigenic response in humans; collagen lacking telopeptides is relatively non antigenic (L ins enmay er , 1982) but can stil l be made to form fibrils Materia l s f ormed by fibril regeneration are of ten to hydrated and additional methods such as freezedrying o cell-induced contraction must be used to give a functional product. Other non-native fibrous aggregates, terme FLS collagen, can be formed in which the collagen molecule are arranged in various staggered arrangements wit the orientation of the molecules in both directions. Quasi-crystal line aggregates can also be formed These include very smal l crystal lites of col lagen termed SLS collagen, in which the collagen molecules all have the same orientation, but there is no stagge between molecules. These have been of partial use i deducing the native structure of collagen but SLS collage

has been of little use in the manufacture of larg structures l ike biomedica l products. Also, quasi crystal line tactoids of col lagen can be prepared, usin conditions simil ar to those used f or reconstitutin fibrils by heat gelation (Leibovich and Weiss, 1970; Le and Piez, 1983) but the technique of production is mor dif ficult than the technique described here as i does not inv o l v e simp l e precipitation. In thes structures the collagen is arranged in a staggered for similar to native fibrils. In the present work th t actoid s ar e produced by a new procedure precipitation by soluble, neutral polymers. bJ h e n collage is precipitated by other procedures, for example salts alcohols or heat, amorphous precipitates are formed. DESCRIPTION OF THE INVENTION During a search f or more ef f ic i ent methods o isolating soluble collagen it was found that the addition o water soluble polymers to a solution of col lagen resulte in an ef ficient precipitation of the col lagen fro solution and the precipitated collagen was found to be muc easier to separate f rom the liquid phase than wit precipitates of col lagen f ormed by the use of salts alcohol or heat. The polymers had other advantages whe compared with these previousl y used precipitant including that they were non-denaturing and did no require removal prior to chromatography o el ec t r oph or e s i s . It was an unexpected finding that the col lage had precipitated in the form of small, needle like, qua si -cr ys ta 11 ine tactoids which were visible unde the light microscope. It was a further unexpected disco v er y that th tactoids could be induced to form into larger assemblage either by al lowing the suspension to mature for a perio of time or by mechanical action, and that the tactoids o their assemblages could be formed into shapes. Accordingly, the present invention provides a metho of producing a col lagen product comprising forming a

aqueous solution containing dissolved collagen and a wate soluble or miscible polymer adapted to precipitate the collagen out of solution in the form of tactoids. The pH of the said solution is pref erably 3.5-1 more preferably 5-8 with 7-8 being still more preferred an about 7.5 being most preferred. The collagen precipitate may be left in the form o a paste or slurry and used in this f orm or afte concentration by any one of the methods gravitationa precipitation, filtration, cen tr if uga ion or the like. Th precipitate may be crosslinkεd, tanned or stabilised b one or more of chemical, physical or biochemical method either bef ore or af ter it has been concentrated C r o s s 1 i n k i n g , tanning or stabilisation applied to th precipitate bef ore concentration makes the tactoid resistant to def orming actions such as heating pressure or biochemical degradation. Cross l inking tanning or stabilisation applied to the precipitat after concentration causes the structure f orme during the concent ation process to become more stable. The so precipitated collagen may also be f ormed for example, into a synthetic body part. Such f ormin into a synthetic body part may be effected b gravitational precipitation, f iltration, centifugation moulding, pressing, shaping or any other way or combinatio of ways. Shapes which may be prepared include sheets tubes, strings and rods. It has been found particularly desirable to form th so precipitated collagen into sheets for use a synthetic dressings for wounds and into tubes for use a synthetic tubular body parts. The sheets can b formed by centrifugation in a large basket centrifuge o the like or by gravitational precipitation or filtration Other methods of producing the sheets are also possible A more compacted sheet is produced by centrifugatio in comparison with gravitational precipitation o filtration. Tubes can also be prepared by cεntrifugatio

or by casting, ou ic'ing or shaping. T he c o l l a g en m a y b e p r e c i p i t a t e d o n t o suitable substrate to form a composite material. Such substrate, onto which the col lagen is precipitated, may ha the form of a particular body part or biomedi;εl product. The substrate may take the form of a matrix. The substrate may take the f orm of a plastic other synthetic surf ace in the f orm of a sheet, tube mesh, onto which the col l agen is directly deposit forming a col lagenous coating. The substrate may a l so take the f orm of a composit f or e x amp l e , v ar ious s y nth et ic l a y er s b onded to a artificial ly or natural ly-produced matrix. The se c o l l agen c o a te d subs tr a te s m a y a l so b chemica l l y modif ied. For examp l e, g l utara l dehyde similar chemicals may be used to stabilise the matrix. The col lagen of the present invention may be used as paste or sl urry. Such a paste or sl urry wou l d ha v e a numbe of applications including as an impl ant material such as t h e f o rm of a n i n j e c t a b l e me di um f or u s e i n co sme t i surgery. Such a slurry may be stabilized chemically such by g l utara l dehyde or irradiation. Such as with gamm radiation. The concentration of this tactoidal col lagen i the paste or sl urry is pref erab l y not l ess than 10 mgm/ml more preferably not less than 30 mgm/ml and most preferabl not less than 40 mgm/ml. The col lagen useful for forming the col lagen product of this invention inc ludes col lagen derived from hides skins or other col lagen containing organs or tissues o humans or other vertebrates or invertebrates and include co l l agens of one type or mixtures of types. So lub l co l l agen can be prepared by enzymic treatment of col l age from those sources. Suitable enzymes include pepsin. The col l agen may a l so be deri ved f rom the cu l tur medium of cel ls, tissues or organs grown in cel l- or tissue culture. The culture medium used to produce the col lage may be a cu l ture medium f rom ce l l or tissue cu l tur deri v ed f rom a person f or whom a synthetic body part i

to be produced; it is believed that doing this will substantial ly reduce the likel ihood of re ection. Further, it is also possible that a substrate may be introduced into the culture medium such that collagen and other components will be directly produced thereon. Such a substrate may have the form of a particular body part or biomedical product desired. The substrate may take the form of a matrix. The substrate may take the form of a plastic or other synthetic surface in the form of a sheet, tube or mesh, onto which the collagen and other components are directly deposited forming a collagenous coating. The substrate may be formed from aggregates of tactoidal collagen of this invention. The water soluble or miscible polymer is preferably a neutral polymer. Such polymers may be at least one of the synthetic polymers polyvinyl alcohol, polyethylene oxide, pol y v iny 1 py rro lidi non e , po 1 y a cr y 1 ami d e , polyethylene glycol, poly ropylene glycol, polyvinyl methyl ether, maleic anhydride copolymers and the like; or at least one of the modified, natural, neutral polymers hydroxyethyl starches, methyl cel lulose, h d r o x y m e t hy 1 cellulose, hydroxyethyl cellulose, hy dr o xy pr op y 1 cellulose or the like; or at least one of the natural neutral polymers agarose, dextrins , dextrans, starches , pectins , alginates and the like. Mixtures of such polymers may be used and the molecular weight of the polymer or polymers can vary over a wide range provided the polymer remains soluble or miscible with water. This l ist of pol ymers is not exhaustive as the important factor is the use of a water soluble polymer or polymers to precipitate the col lagen. Neutral water soluble or miscible polymers are preferable but charged, water soluble polymers may also be used particularly if they are only mildly charged. The precipitate of collagen is generally found to be improved if it is al lowed to stand in said solution. Such standing is preferable for a period of one hour to six months with one day to one month being more preferred.

Such standing is ef f ected at temperatures betwee the denaturation temperature of the col l agen and th freezing point of the solution; preferably at between zer and 20°C; more preferably between zero and 10°C. I f d e s i r e d , a d d e d m a t e r i a l s s u c h a p l astici sers , co l ourants , bio l ogica l l y acti v m a t e r i a l s s u c h a s p r o t e o g l y c a n s o glycosaminoglycans, proteins, other extracel lula products, hormones, growth factors, antibiotics and agent which affect wound healing or have other beneficia ef f ects, ionic strength modif iers such as sa lts, o solids such as insoluble collagen or the like may b i n c l u d e d w i t h t h e s o p r e c i p i t a t e d c o l l a g e n a n incorporated into material made f rom the col l agen. Thes added materials may also . be incorporated into th solution of soluble col lagen before addition of th polymer or otherwise incorporated into materia l mad f rom the col l agen. Charged, water soluble or wate miscible polymers may be used as part of a mixture wit the neutral polymer or polymers and added to the solubl col lagen with the neutral polymer sol ution. Thes charged polymers may be used to modify the properties o the soluble collagen solution or the material made fro the precipitated collagen. The co l l agen product o f this in v ention may b chemica l l y or biochemica l l y stabi l ised. Biochemica stabilisation may be ef f ected by enzymes such a lysyl oxidase. Chemical s abilisation may be effecte by tanning agents, syntans, other cross-linking agent or chemica l modif iers of co l l a gen. Of particu l a interest are stabilisers which limit proteolysi or the immunogenicity of the co l l agen Glutaraldehyde is a stabiliser of particular interest The product may also be stabilised by dehydration by mil heat, water miscible sol vents, critical point drying or th like. Such stabilisation may be performed before or after shaping operation. The col lagen product of thi invention may be sterilised chemically or by irradiation

Chemical sterilisation may be conducted by means of suitable solutions of sterilising materials such as lutaral ehyde from between ϋ.5% to 5% concentration. The product may be stored in solutions of sterilant until required f or use. Steri lisation by means of irradiation can be conducted by exposing the col lagen product of this invention to gamma rays from a suitable source. From 0.5 to 5 Mrads of irradiation may be used, preferably 2.5 Mrads of gamma ray irradiation is suitable for satisfactory sterilisation of the product. The tactoids formed by precipitation of the soluble col lagen in this invention are useful in production of synthetic body parts, and other materials for medical or veterinary applications. The collagen tactoids or tactoid assemblages could be stabilised by chemical or biochemical techniques or could be formed into various useful shapes and then stabilised. The tactoidal collagen has potential application in many areas such as the manufacture of collagen sponges or haemostatic agents , of dressings, of membranes, of skin, of tubes and the like and in the treatment of disease such as peridontal disease. The tactoida l collagen can also be used in conjuction with other structural type materials to form composite materials with diff erent properties. For example, a tube of tactoidal collagen can be covered with a woven or knitted mesh of fibre such as Dacron to give the tube additional strength. Alternatively, the tactoidal collagen can be formed into a tube surrounding the mesh to give a more intimate contact with the mesh and better properties. To better utilise the properties of the tactoidal collagen in the formation of artificial body parts it is possible to arrange the tactoids in a preferred orientation by the application of an electric field or by means of mechanical action. Materials made from the oriented tactoids may have beneficial effects in the healing of wounds. Many other methods of utilising the tactoidal collagen in a variety of shapes and forms

and in conjuction with diverse other materials can b envisaged. The product of this invention also has applicatio in areas outside medical and veterinary product including plastics, fabric, leather or as composites or th like . The present inv ention a l so inc l udes suc col lagen products and articles produced therefrom. The col l agen products of this in v ention ha v advantages over presentl y avail abl e products. Thes include, low immunogenicity, ease of preparation, hig collagen content, and strength. The fol lowing examples il lustrate the invention. EXAMPLE 1 Type I collagen was solubilised and extracted fro f oeta l ca l f skin by pepsin digestion and purif ied b fractional salt precipitation according to the metho of Trelstad et al.(1967). This purified collagen wa dissol ved in 200 m Tris-HCl buffer pH 7.5 at 4°C and a a concentration of 10 mg/ml. Polyethylene glycol (PEE 4000 was than added to produce a final concentration o 2.5? (w/v). A precipitate of tactoidal collagen forme which settl ed to the bottom of the container af te standing at 4 ° C f or a few hours or could be concentrate by filtration or c en t r i f u g a t i on . EXAMPLE 2 As for Example 1 except that the concentratio of the collagen was 1 mg/ml. EXAMPLE 3 As for Examp l e 2 except that PEG 400 to a fina concentration of 3.5% (w/v) was used to precipitate th collagen. EXAMPLE 4 Type III collagen, solubilised and extracted as i Exampl e 1 , was dissol ved at a concentration of 1 mg/ml i 200mM Tris- HC1 buffer pH7.6 at 4°C. PEG 400 was added t the solution to a final concentration of .0? (w/v) an the precipitate of tactoidal collagen formed.

EXAMPLE 5 As for Example 4 except that a final concentration of 2.5? (w/v) PEG 4000 was used. EXAMPLE 6 Type II collagen was isolated by the method of Trelstad et a 1. (1976) from bovine articular cartilage by pepsin so 1 ub i 1 isat ion and fractional salt precipitation. The purified type II collagen was dissolved in 200 mM Tris- H-Cl buffer at pH 7.-6 at 4°C and at a concentration of 1 mg/ml. PEG 400 was then added to produce a final concentration of 3.0? (w/v). The precipitate of tactoidal collagen formed as in Examples above. EXAMPLE 7 As for Example 6 except that PEG 4000 was added to a final concentration of 2.0? (w/v). EXAMPLE 8 As for Example 1 except that PEG 1000 to a f ina l concentration of 5? (w/v ) was used to precipitate the collagen. EXAMPLE 9 As for Example 1 except that PEG 10000 to a f ina l concentration of 5? (w/v ) wa s used to precipitate the collagen. EXAMPLE 10 The suspension of tactoidal collagen from Example 1 was stored at 4°C for 4 weeks and col lected on Whatman No. 1 filter paper in a 125 mm diameter basket centrifuge rotating at 4000 rpm. The resulting collagen sheet was removed from the centrifuge and separated from the filter paper. The collagen sheet was found to have properties similar to those of a thick, wet paper tissue and to be suitable for assisting in the healing of open skin wounds. EXAMPLE 11 The collagen sheet, prepared as in Example 10, was tanned using a solution of 0.01? glutaraldehyde for 18 hours. After drying the sheet was found to have a

tensi l e strength of 6.2N/sq cm and an e l ongati on of 1 at a moisture content of 16?. EXAMPLE 12 The col lagen sheet, prepared as in Example 10 w sealed in a polyethylene bag and subjected to 2.5Mra of gamma ray irradiation. The sheet was found to hav been sterilised and to have improved tensile properti over those of the sheet in Example 10. EXAMPLE 13 As for Example 2 except that the buffer was at pH5. EXAMPLE 14 As for Example 1 except that the collagen extracte from foetal calfskin was not purified by fractio salt preci itation but was used as a crude extract and tha 5? PEG 4000 was used. EXAMPLE 15 As for Example 14 except that 5? polyvinyl alcohol wa used . EXAMPLE 16 As for Example 14 except that 5? dextran of 10,00 average molecular weight was used. EXAMPLE 17 As for Example 14 except that 5? dextran of 40,00 average molecular weight was used. EXAMPLE 18 A collagen sheet prepared as in Example 10 was rolle into a tube and then stabilized by tanning using a solutio of 0.01? glutaral eh de for 18 hours. EXAMPLE 19 A co l l agen sheet prepared as in Examp l e 10 was dried b critical point drying using l iquid carbon dioxide. BIBLIOGRAPHY Ch v api l , M . ( 1979 ) - I n "F ibr ou s P ro teins Scientif ic, Industria l and Medica l Aspects", V o l . 1 (Ed Parry, D.A.D. and Creamer L.K.) Academic Press , London p 247-269. B o r n st e in , P . an d T r a ub , l . ( 1 979 ) I n "Th Pr ot ein s" V o 1 4 ( E d s N eu r a t h , H. a n d H i l l , R.L. Academic Press, New York pp411 -632.

1 Linsenmeyer, T.F. (1982) In "Collagen in Health and

2 Disease" (Eds Weiss, J.B. and Jayson, M.I.V.) Churchill

3 Livingston, Edinburgh pp244-268.

4 Leibo v ich. S.J. and Weiss , J.B. (1970) Biochim.

5 Biophys. Acta 214:445-465. Electron microscope studies of

6 the effects of εndo- and e o - p ep t id a s e digestion on

7 tr opocoll agen .

B Lee, S.L. and Piez, K.A. (1983) Col lagen Rel. Res.

9 3:98-103. Type II col lagen from Lathyritic rat 0 chondr osa rcoma : preparation and in vitro fibril formation. 1 Trelstad, R.L., Catanεse, V . . and Rubin, D.F. (1976) 2 Ana l. Biochem. 71 :114-118. Col lagen f ractionation: 3 Separation of native types I, II and III by dif ferential 4 precipitation. 5 Modifications and adaptations may be made to the 6 above described without departing from the spirit and scope 7 of this invention which includes evεry novεl feature and B combination of fεatures disclosed herein.