US 3435825 A
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April 1, 1969 1 A. 'rl-lol-:NmsA
PLASTIC COLLAGEN SUTURES Filed nec. 1'?,` 1962 CHROM/C XDE INVENTOR.
Jaw/ence sfgoennes BY% Q United States Patent C) 3,435,825 PLASTIC COLLAGEN SUTURES Lawrence A. Thoennes, Chicago, Ill., assignor to The Kendall Company, Boston, Mass., a corporation of Massachusetts Filed Dec. 17, 1962, Ser. No. 245,061 Int. Cl. A61] 17/00; D01f 5/00 U.S. Cl. 12S-335.5 10 `Claims ABSTRACT OF THE DISCLOSURE This application is concerned with plastic collagen sutures, specifically with chrome tanned sutures having the usual strength and body absorption properties characteristic of chromicized sutures but unlike such sutures having sufficient plasticity to permit easy removal of set bends therefrom by the usual stretching procedure employed tby surgeons.
It is a characteristic of collagen sutures, tanned to increase strength and body absorption time, to assume a permanent set when stored in the form of coils or in turns upon a reel in a confined package. Numerous softening agents including water and various plasticizers have been applied to such tanned collagen sutures in attempts to eliminate this tendency or at least to permit the easy removal of set bends when the surgeon stretches the suture. However, all such softening agents or plasticizers when used in suflicient `amounts to be completely effective have seriously weakened collagen sutures so that tanned sutures as sold prior to this invention have been only partially plasticized. If one observes such tanned collagen sutures after stretching in the manner employed by surgeons, the suture begins to retract as soon as the stretching force is removed and soon assumes an elongated form of the configuration it had when stored in the confinement of the suture tube or package.
It is an object of this invention to provide tanned collagen sutures comparable in body absorption time and strength characteristics to usual chromicized `sutures but which, when stretched from a coil-like configuration in the usual manner employed by surgeons, exhibit a very much reduced tendency to return to the original coiled form.
FIGURE l illustrates a coiled suture in a typical suture package.
FIGURE 2 illustrates a portion from a coil as in FIG- URE l of the usual Chromed collagen suture after a 60- inch length has lbeen stretched with a 3-pound pull and allowed to relax for 5 minutes.
FIGURE 3 illustrates a portion from a coil as in FIG- URE 1 of a collagen suture of this invention after a 60- inch length has been stretched with a 3-pound pull and allowed to relax for 5 minutes.
FIGURE 4 illustrates graphically the difference in elongation of coiled tanned collagen sutures of various chrome content, previously stored in water and 90% ethanol, after such stretching.
The objects of this invention are obtained by treatment of raw collagen strands with a combination of two compounds in solution preferably in succession and preferably in a given order. Satisfactory results may be obtained, however, by treatment with the two compounds Patented Apr. 1, 1969 combined and reacted into a single treating solution or by treatment with the compounds successively in the reverse of the preferred order.
In the preferred method of treatment, the raw collagen strand is first treated by immersion in a solution of a dichromate. Sodium dichromate is the preferred dichromate ibut potassium dichromate, calcium dichromate, am monium dichromate or any other dichromate soluble to the extent of .01% in water at room temperature is suitable, it being necessary only that the dichromate ion be in suiiicient concentration in the water. A pH of 5 to 6V: is preferred. In tanning collagen strands according to this method, the ratio of volume of solution to the weight of the strand has little effect provided there is sufficient dichromate and reducing agent in solution. With concentrations of 0.1% sodium dichromate and 0.2% pyrogallic acid, volume-weight ratios between 30-1 and 200-1 give very little difference in the final chrome content of the suture or the degree of plasticity produced when the time of immersion is maintained constant between 1 to 2 hours. With extremely dilute solutions of .01% or less, a longer period of immersion is necessary, being roughly inversely proportional to the concentration of dichromate ions in the solution. With a solution of .0025% dichromate, a l2-hour `bath followed by a 2-hour bath in .034% pyrogallic acid gave a chrome content equivalent to that of an amount of chromic oxide .174% of the dry Chromed suture weight.
After the proper period of immersion in the dichromate bath, the solution is drained and replaced with a second bath of a solution of the phenol derivative defined below preferably having at least a mole to mole relationship with the dichromate in an equal volume bath. The preferred ratio of concentrations of the dichromate and phenol derivative solutions is when the first bath is a solution of sodium dichromate and the second of equal volume is a solution of pyrogallic acid.
The phenol derivative is one or more of those selected from the group consisting of compounds corresponding to the formulae where R is a hydroxyl or an amino group and X is any radical chosen from the group consisting of hydrogen, hydroxyl, amino, an alkyl of less than 5 carbon atoms, carboxyl, nitro and carbalkoxyl radicals.
Afer immersion for from l to 3 hours -with 2 hours preferred in the phenol derivative bath in the preferred molar relationship, the collagen strand will have been properly tanned and will be found to have a chrome content equivalent to that of chromic oxide in the range of .1 to .3% of the dry chromed suture. The method of measuring the chrome content of the tanned collagen strand in terms of chromic oxide is as follows:
Ash .8 gram of dried Chromed collagen strand at 500 C. When cooled, boil the ash in an Erlenrneyer fiask with 10 cc. of perchloric acid for 10 minutes after the liquid turns orange. Cool and dilute to about 200 cc. with distilled water. Boil for 20 minutes, then cool to 65 F. Add 15-20 cc. of concentrated hydrochloric acid and 10 cc. of potassium iodide solution made by dissolving grams in 500 cc. of water. Titrate with standardized sodium thiosulphate solution until the solution is pale yellow. Add
a few drops of starch indicator and titrate to the disappearance of any blue coloration. Calculate cc. of Na2S2O3XFactorXl00 Wt. of sample Factor is that obtained by multiplying the normality of Nagsgog The preferred chrome content of the tanned collagen strands of this invention is equivalent to that in an amount of chromic oxide in the range of .15% i.05% of the Weight of such strand. This is in distinct contrast with the chrome content of chrome tanned collagen strands prior to this invention, the chrome content of which was normally equivalent to that of chromic oxide in amounts Percent Chromic Oxide:
4 tionship with the dichromate concentration. Where the bath volume in cc. to the collagen weight in grams is in the range of 200 to 1, a phenol derivative concentration of .2% is preferred. With dichromate concentrations in the range of .05% to .2%, a two-hour bath produces chromicized collagen sutures with chrome contents equivalent to that of chromic oxide in the range of .17 to .2% of the dry chromicized suture. One may reduce the chrome content by reducing the bath period or one may reduce the chrome content by retaining the two-hour bath period and reducing the dichromate concentration below .05% and down to about .03% to obtain sutures with chrome contents equivalent to chromic oxide in amounts as low as .1% of the dry weight of the chromicized suture.
about .5% and frequently in amounts as much as 2% of 15 One may also increase the chrome content above the the dry Weight of the tanned collagen strand. equivalent of .2% chromic oxide without modifying the It has been discovered, however, that the proportion single bath by increasing the period thereof so that at about of chrome equivalent to that of chromic oxide above .3% 3 hours the chrome content will have increased to the of the dry tanned suture weight does not contribute apequivalent of about .3% chromic oxide. Sutures with preciably to its strength and may delay the rate of ab- Z chrome contents in the range of .2% to .3% equivalent sorption in the body undesirably. Such excess above the chromic oxide are increasingly less plastic as the chrome equivalent amount of chrome in chromic oxide above .3% content increases in this range, however until at .3% of the dry tanned gut does have a very adverse effect on chromic oxide equivalent, the plasticity is barely satisfacthe plasticity of the tanned strand. At .3% chromic oxide tory. One-bath chromicization tends to produce sutures or below, equivalent chrome permits removal of configuwith the degree of chromicization increasing from the cenrations by stretching to the point where they are not parter of the suture outwardly whereas two-bath chromicizaticularly obvious or objectionable with the .3% equivalent tion gives a more uniform through and through chromichrome suture being barely satisfactory. With chrome concization. Moreover, the single-bath method tends to Ibe tents above this equivalent, the set configurations become somewhat gummy so that a cleaning problem is involved increasingly more diicult to remove and constitute a most with regard to the bath tanks. objectionable feature as can be easily observed. When the preferred order of treatment is reversed with Examples of the two-bath method with the first bath the two-bath method so that the collagen strand is first constituting the dichrornate solution are as follows: treated with the phenolic derivative, the results are very TABLE I Chrome 1st bath Concentra- Period (hr.) 2nd bath Concentra- Period (hr.) equiv. to
' tion, chromic percent percent oxide, percent Sodium dichromate 1 1 Pyrogaliic acid 2 2 31 .1 1 do .2 2 .24 .1 1 .2 2 .24 .1 1 .2 2 .24 .1 1 .2 2 .13 .1 1 .2 2 .17 .1 1 .2 2 .21 .1 1 in .2 2 .23 1 1 Orthprotocatechuic 2 2 .14
acl 1 1 Orthoveratrlc acid 2 2 17 1 1 Amino phenol 2 2 16 1 1 Chestnut extract. 2 2 21 1 y Pyrogallic acid 2 2 03 .1 d .2 2 .21 .1 1 .2 .29 .025 2 .2 2 .13 .025 1 .2 2 .1 .02 4 .2 2 .3 .01 4 .2 2 .1 .1 1 .1 4 .4 .o5 1 .3 1 .17 .05 1 .1 4 .16 .o5 1 .2 2 .13 .05 1 .2 2 .11 05 1 Hydroquinone 2 2 14 The accompanying graph FIGURE 4 illustrates average increase in length in inches 1 minute after momentarily stretching with a 3-pound pull, 60-inch pieces of collagen suture of various chrome content stored in the form of circular coils of 11/2 inches in diameter for a minimum period of 1 Week in tubing fluid of 10% water and 90% ethanol.
When the one-bath method of chromicization is utilized in accordance with the invention, the phenol derivative concentration is preferably in excess of the molar relacomparable with the results obtained when the strand is first treated with the dichromate but it takes less dichromate to accomplish the same results. That is, where the period and concentration of each bath is unchanged but the order is reversed, the procedure in which the phenolic derivative bath is first, produces sutures with higher chrome content. For that reason it is preferred to use the dichromate bath first since any error is less significant.
Typical of two-bath methods involving a phenolic derivative first bath are the following:
TABLE II Concentra- Concentra- Chrome 1st bath 'on, Period (hr.) 2nd bath tion, Period (hr.) equiv. to
percent percent chromic oxide, percent Pyrogallic acid 2 2 05 1 32 Do 2 2 025 1 21 Do 2 2 01 1 09 The particular tubing fluid used in storing collagen sutures of this invention has considerable effect upon the plasticization of the suture. Water is normally considered a good plasticizer for collagen sutures but both ethyl and methyl alcohol in that order are superior plasticizers for such sutures when plasticity is measured by plastic elongation. Thus sutures chromicized in accordance with this invention may be obtained in more plastic condition with higher percentages of ethyl or methyl alcohol combined with lower percentages o'f water than are usual in 0 tubing fluids. A tubing Huid made up of a solution of 98% ethyl alcohol and 2% water to which is added .3% of ethylene oxide as a sterilizing agent is preferred. The sutures of this invention in the preferred range of chrome content equivalent to that in chromic oxide in the range of .1% to .2% of the dry weight of the suture are more plastic than plain untanned or non-chromicized sutures. Thus in the tubing solution of FIGURE 4 which was 90% ethyl alcohol, 10% water to which was added .3% ethylene oxide, 60-inch plain sutures averaged 1 inch increase in length when stretched for a minute with a 3-pound pull whereas sutures with chrome content equivalent to .1 to .2% of the dry weight of the suture stretched more. As a more dramatic:` illustration of the superiority of chromicized sutures of this invention over plain sutures in the matter of plasticity an experiment was performed using ive 10-foot strands of #1 catgut. The strands were cut in half and half of each strand was left untreated or plain and packaged in 2. cc. of preferred tubing solution. The other half of each strand was treated with a solution of .04% sodium dichromate for one hour after which the solution was drained and replaced by a solution of .034% pyrogallic acid solution for two hours which was also drained. These treated sutures were later determined to have a chrome content equal to that in chromic oxide in the amount of .17% of the dry weight of the suture. These suture halves of the 10-foot original strands were then packaged in 2 cc. of the same tubing iiuid as the plain halves. After one week the packages were opened and the sutures were tested for plasticity by stretching the G10-inch lengths for l minute with a -pound pull and measuring the increase of length after release. The plain suture halves had an increase in length of 1.15 inches whereas the suture halves treated in accordance with this invention had an increase of 2.16 inches. With 45 sutures of greater chrome content, the eiect of tubing uid is less pronounced. A suture having a chrome content equivalent to that of chromic oxide in an amount .3% of the dry weight of the suture was elongated .9 inch under the test conditions when tubed in 90% ethyl alcohol and 10% water to which .3% ethylene oxide was added as in FIGURE 4. When a similar suture was tubed in the preferred solution, its elongation under the same conditions was 1.3 inches.
No. 1 sutures prepared by the usual chromicizing meth- 55 ods and having an average chrome content equivalent to that in chromic oxide in amount of 1% of the dry suture weight were compared with No. l sutures prepared in accordance with this invention and having an average chrome content equivalent to that in chromic oxide in amount of .17% of the dry suture weight as follows:
TABLE III Chrome equiv. Straight pull Straight pull Knot strength to chromic oxide, dry (pounds) wet (pounds) (pounds) percent Straight pull after indicated days in animal tissue (pounds) 0 days 7 days 14 days 21 days 28days 42 days 70 Chrome equiv. to chromic oxide, percent I claim:
1. An absorbable chromicized raw collagen suture 75 comprising the reaction product of a raw natural collagen strand of the size and shape of a suture, a dichromate salt having a solubility in water of at least 0.01% at F. and a phenol derivative selected from the group consisting of compounds corresponding to the formulae wherein R is a member selected from the group consisting of hydroxyl and amino, and X is a member selected from the group consisting of hydrogen, hydroxyl, amino, nitro, carboxyl, carbalkoxyl and loweralkyl having 1 to 5 carbon atoms, such that said reaction product has a chrome content equivalent to that in chromic oxide weighing in the range of 0.1% to 0.3% of the dry weight of the suture.
2. An absorbable chromicized raw collagen suture according to claim 1 wherein the dichromate salt is a member selected from the group consisting of sodium dichromate, potassium dichromate, calcium dichromate and ammonium dichromate.
3. An absorbable chromicized raw collagen suture according to claim 1 wherein the chrome content of the reaction product is equivalent to that in chromic oxide in the range of 0.1% to 0.2% of the `dry weight of the suture.
4. An absorbable chromicized fraw collagen suture according to claim 1 wherein the phenol derivative consists of pyrogallic acid.
5. A method of producing an absorbable chromicized raw collagen suture comprising the steps of reacting a strand of ra-w natural collagen with a dichromate salt having a solubility in water of at least .01% at 70 F. and a phenol `derivative selected from the group consisting of compounds corresponding to the formulae X X X R and X X X X wherein R is a member selected from the group consisting of hydroxyl and amino, and X is a member selected from the group consisting of hydrogen, hydroxyl, amino, nitro, carboxyl, carbalkoxyl and loweralkyl having 1 to 5 carbon atoms, such that the reaction product has a chrome content equivalent to that in chromic oxide weighing in the range of 0.1% to 0.3% of the dry weight of the suture.
6. A method in accordance with claim 5 wherein the raw natnural collagen is -rst treated with the dichromate salt followed by treatment with the phenol derivative.
7. A method in accordance with claiml 5 wherein the raw natural collagen is rst treated with the phenol derivative followed by treatment with the dichromate salt.
8. A method in accordance with claim 5 wherein the raw natural collagen is treated with a solution of the reaction product of the dichromate salt and the phenol derivative.
9. A method in accordance with claim 5 wherein the dichromate salt is a mem-ber selected from the group consisting ofsodium dichromate, potassium dichromate, calcium dichromate and ammonium dichromate.
10. A method in accordance with claim 5 wherein the dichromate salt consists of sodium dichromate and the phenol derivative consists of pyrogallic acid.
(References on following page) 7 8 References Cited by British Leather. Manu. Rec. Assoc., London, England,
T5965 B75. UNITED STATES PATENTS Gustavson: The Chemistry and Reactivity of Colla- 542,971 7/1895 Amend 8 9426 gen, pages 171, 172, 192-196, Pub. 1956 by Academic 987,750 3/1911 Seyewitz et a1 8 94.33 5 Press, 111C-, QD 431G8 2,519,404 8/195() Rynkiewicz 12g 335 5 Shuttleworth: J. Int. S-oc. Lea. Trades Chem., pages 2,576,576 11/1951 Cressweu et a1. 12s-335.5 281-282 8/94-27- 2,640,752 6/1953 Davis 8 9411 Wllson: The Chemlstry of Leather Manufacture, pages 3,093,439 6/1963 Borhweu 8 94,11 649-650, 690-696, Pub. 1929, vol. II, by The Chem. 2,475,697 7/1949 Cresswen 264-202 10 Catalog Company, Im, N.Y.C., T5965 W5 1928.
OTHER REFERENCES DONALD LEVY, Primary Examiner.
Dempsey: Progress in Leather Science, Chapter One, l US- C1. X-R- The History of Hides and Skins, pages 3-7, Pub. 1948, g 94 11 UNITED STATES PATENT OFFICE CERTIFICATE 0F CORRECTION Patent No. 3,435,825
April 1, 1969 Lawrence A. Thoennes It is certified that error appears in the above identified stent and that said Letters Patent are hereby corrected as P shown below:
Column 6, line l, before "a" insert applying to line 59, natnural should read natural Signed and sealed this 14th day of April 1970.
WILLIAM E. SCHUYLER, JR.
Edward M. Fletcher, Jr.
Commissioner of Patents Attesting Officer