|Publication number||US3331814 A|
|Publication date||Jul 18, 1967|
|Filing date||Jul 15, 1963|
|Priority date||Aug 24, 1962|
|Publication number||US 3331814 A, US 3331814A, US-A-3331814, US3331814 A, US3331814A|
|Inventors||Arthur Randall Alan|
|Original Assignee||Courtaulds Ltd|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (3), Referenced by (17), Classifications (22)|
|External Links: USPTO, USPTO Assignment, Espacenet|
United States Patent 3,331,814 SYNTHETIC POLYPEPTTDES OF AN L-IMINO ACID AND AN L-AMINO ACID Alan Arthur Randall, Maidenhead, England, assignor to Courtaulds Limited, London, England, a British com- P y N0 Drawing. Filed July 15, 1963, Ser. No. 295,223 Claims priority, application Great Britain, Aug. 24, 1962, 32,561/62 4 Claims. (Cl. 260-78) This invention is concerned with synthetic polypeptides which are hydrolysable by enzymes and which may be formed into filaments or films.
In the practice of surgery, a strand or filament used to sew together the open parts of a Wound, is referred to as a suture; when used to tie blood vessels it is known as a ligature. The word suture is used in this specification to refer to both sutures and ligatures.
Sutures are either absorbable or non-absorbable. The only completely absorbable suture is of animal origin and is known, generically, as cat-gut. This material is composed largely of the protein collagen, which is absorbed o digested, during the healing process, by the tissues in which it is embedded. The absorption is brought about by proteolytic enzymes in the tissues which hydrolyse the collagen into its component amino acids which are readily metabolised.
The rate of proteolysis of collagen can be slowed by tanning the protein, as is done, for example, in the production of chromicised cat-gut. In this way, a number of sutures having difierent life-spans in proteolytic environments, may be derived :from a single sample of raw cat-gut, simply by varying the severity of the tanning process.
We have made a fibre-forming synthetic polypeptide which has a property similar to that of collagen, in that it is subject to proteolysis.
Accordingly, the present invention is a polypeptide subject to proteolysis, comprising a copolymer of an L-imino acid and an L-amino acid.
L-proline and L-hydroxyproline are the preferred imino acids and they may be used in conjunction with such amino acids as L-glutamic acid and L-alanine in forming the polypeptide.
The rate of proteolysis of the polypeptide increases with the proportion of the imino acid component and it is merely a matter of experiment to discover the ratio of imino acid to amino acid residues which endows the polypeptide with a desirable resistance or susceptibility to proteolysis.
For use in sutures, the polypeptide need contain no more than from 5 to 15 percent of the imino acid, but it is also possible to slow the rate of proteolysis of the polypeptide containing this amount or more of the imino acid by tanning, as is done for cat-gut by transforming it to chromicised cat-gut for example.
We have made the polypeptide from a mixture of the N-carboxyanhydride derivatives of the amino-acid and the imino acid. The mixture is reacted in an inert solvent for the polypeptide to form a viscous solution with evolution of carbon dioxide. The solution of polypeptide may then be extruded to form filaments or films by contact with a coagulant o1- evaporation of the solvent, i.e. using ice wet spinning or dry-spinning techniques. The films and filaments are strengthened and rendered less soluble by stretching.
The filaments are useful sutures and the films may be sliced to form sutures or used as absorbable panels in surgery.
The invention is illustrated by the following example.
EXAMPLE A mixture of 1 gram of L-proline N-carboxy anhydride and 11.93 grams of 'y-methyl L- glutamate N-carboxy anhydride was dissolved with warming in a mix ture of ethyl acetate (19.4 ml.) and methylene chloride (35.8 ml.). The initiator, 9.5 ml. of N/lO tri-n-butylamine in methylene chloride, was added and the polymerisation took place over a period of 15 hours at 40 C.
The polypeptide solution could be cast into films or spun into filaments by extrusion into coagulants such as ether or ether/ acetone mixtures. The unstretched filaments were found to be insoluble in water, readily soluble in dichloroacetic acid and trifluoracetic acid, and sparingly soluble in glacial acetic acid, formic acid, chloroform, methylene chloride and N,N-dimethyl formamide. The filaments were stretched by 400 percent and this has the effect of reducing their solubility in all the above-mentioned solvents, as well as increasing the filament tenacity to 1.6- gram/ denier.
The absovbability of the sutures of the filamentary polypeptide was tested in vitro by incubation in media containing proteolytic enzymes such as trypsin and papain. The method used was that employed by Lennox & Forss (Journal of the Society of Leather Trades Chemists, 36, 322) in their examination of the digestion of tanned collagen by enzymes. The results of these determinations showed that the polypeptide had a rate of proteolysis similar to that of chromicised cat-gut.
When a strand of the polypeptide was immersed in the papain solution at 50 C. for one hour, it sutfered a loss of weight of 11.4 percent.
What Iclaim is:
' 1. A solid, fiber forming, water insoluble polypeptide copolymer capable of proteolysis consisting essentially of an L-imino acid selected from the group consisting of L-proline and L-hydroxy proline and an L-amino acid selected from the group consisting of L-glutamic acid and L-alanine.
2. The copolymer claimed in claim 1 in which the proportion of L-imino acid is between about 5 and about 15% by weight and the proportion of L-amino acid is between about and about by weight.
3. A filament formed from the copolymer of claim 1.
4. A film formed from the copolymer of claim 1.
References Cited UNITED STATES PATENTS 3,052,655 9/1962 Fox et al. 26078 3,076,790 2/1963 Fox et al. 260 78 3,089,749 5/1963 Ballard 260'-78 WILLIAM H. SHORT, Primary Examiner.
H. D. ANDERSON, Assistant Examiner.
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|U.S. Classification||528/327, 528/310, 606/231, 528/315, 528/318, 528/328|
|International Classification||D01F6/58, C08G69/10, C08G69/00, C07K1/02, D01F6/68, A61L17/00, C07K1/00, A61L17/10|
|Cooperative Classification||C07K1/02, D01F6/68, C08G69/10, A61L17/10|
|European Classification||D01F6/68, C08G69/10, C07K1/02, A61L17/10|