US3166074A

US3166074A - Aldehyde, chrome and polyhydric alcohol tanned collagen articles and their production

Info

Publication number: US3166074A
Application number: US284244A
Authority: US
Inventors: Kurilla John
Original assignee: Ethicon Inc
Current assignee: Ethicon Inc
Priority date: 1963-05-29
Filing date: 1963-05-29
Publication date: 1965-01-19
Anticipated expiration: 1982-01-19

Description

Jan. 19, 1965 J. KURILLA CHROME AN ALDEHYDE D POLYHYDRIC ALCOHOL TANNE COLLAGEN ARTICLES AND THEIR PRODUCTION 2 Sheets-Sheefl Filed May 29, 1963 INVENTOR. Aw/v Af/E/AAA KURILLA 9 POLYHYDRIC ALCOHOL TANNED 2 Sheets-Sheet 2 Jan. 19, 1965 Filed May 29, 1963 INVENTOR. 7oA9v 17/244,:

1 g %//A/- ORNEYS United States Patent 3,l66,tl74 nnnnrnznn, orator r: AND eorrnrnnro Asco- HQL TANNED (IQLLAGEN ARTIQLEfi) AND The present invention relates to the treatment of protein material and the product so obtained with particular emphasis on the method of chemically treating substantially pure collagen filaments and strands for surgical uses such as suturing and ligating.

This application is a continuation-in-part of application Serial No. 85,362, filed January 27, 1961.

For the sake of clarity, the terms used herein are defined as follows:

The term tendon collagen fibril as used herein means a thread-like collagen structure derived from beef tendon that is round in cross section. These fibrils in the completely dehydrated state measure about 500 to 2000 Angstroms in diameter.

The term swollen tendon collagen fibril as used herein means a collagen fibril derived from beef tendon that has been swollen in acid solution. The diameters of swollen collagen fibrils range from less than 5000 Angstroms to about 90,000 Angstroms.

The term monofilarnent as used herein means a single thread of oriented collagen fibrils as extruded through a single orifice in a spinnerette.

The term multifilament as used herein means a group of individual separate filaments extruded through a spinnerette.

The term strand as used herein means a group of filaments that have been united to form a unitary structure.

The protein collagen has exceptional tensile strength and is essentially non-antigenic, which properties have resulted in the wide use of substantially pure collagen strands in surgery. It is well known that collagen sutures which have been implanted in the human body are slowly attacked by proteolytic enzymes with a resulting decrease in tensile strength and ultimate absorption. It is also known that the rate of absorption can be controlled by treating the collagen strand with chemical reagents such as chromium salts. Thus, chromium treated sutures have been prepared from sheep intestines which retain onehalf of their original tensile strength from 7 to 10 days after implantation.

A particular problem exists, however, in the case 0 extruded collagen strands. lthas been noted that collagen strands obtained by extruding a dispersion of'collagen fibrils into a coagulating bath are characterized by a rapid in vivo digestion. Thus, a collagen suture prepared under conditions that involve swelling collagen fibrils in acid solution, extruding the swollen collagen fibrils to form a filament and subsequently dehydrating the swollen collagen fibrils is more rapidly attacked by proteolytic enzymes than sutures prepared from sheep intestines.

' It is an object of the present invention, therefore, to chemically modify collagen and thereby increase its resistance to enzymatic degradation.

it is another object of the invention to provide 'a chemically treated extruded colagen suture having a suitable wet tensile strength.

Still another object of the invention is to produce an extruded chemically treated absorbable collagen suture that will retain sufficient tensile strength under the conditions of use to accomplish its purpose and be absorbed in the body after the wound has healed when the suture is no longer necessary. 7

The present invention provides a method of'chem-ically treating a continuously extruded collagen strand to provide the desired strength, in vivo digestion time and uniformity of product. The process is characterized by treating a bonded collagen multifilament consecutively with at least two different solutions. The first solution is a solution of a polyhydric phenol such as pyrogallol and/or an oxidized polyhydric phenol such as 1,4-naphthaquinone and the second solution is an acid solution of a chromium salt and an aldehyde such as formaldehyde. The use of a third solution containing an alkaline solution of formaldehyde to treat the moving strand is optional.

The first solution of polyhydric phenol and/ or quinone, if used alone, provides a collagen strand which has inadequate initial wet strength and which has an excessively rapid rate of in vivo tensile strength loss. However, when this treatment is followed by the second solution containing formaldehyde, the said rate is decreased. It is known that formaldehyde alone will increase the intial wet strength of collagen, but if formaldehyde alone is used in the amount required for adequate in vivo properties, the strand is embrittled and the knot strength is lowered. By treating the strand consecutively with a polyhydric phenol and/or quinone solution and a formaldehyde solution, the rate of tensile strength loss may be greatly improved without embrittling the strand.

The purpose of the chromium in the second bath is to increase the intial wet tensile strength of the final strand. Chromium alone has only a minor effect on the rate of tenshe strength loss of the collagen at the concentration employed in the present invention.

a it will be understood by those skilled in the art that equivalent results would be obtained if the order of the solutions were reversed and the collagen was first treated with a chromium formaldehyde solution and then treated with the polyhydric phenol and/0r quinone solution. Also, the formaldehyde and chromium can be applied separately in different solutions. 7

The invention will appear more clearly from the following detailed deseription when taken in connection with the accompanying drawings, which show by way of example, preferred embodiments of the inventive idea. Referring now to the drawings,

FIGURE 1 illustrates a machine designed to continuously tan a bonded collagen multifilament.

FIGURE 2 is a detailed perspective view of apart of the machine illustrated in FIGURE 1 showing the godet 21 which takes up the tape from the supply reel. This figure also shows the auxiliary roller 31 which is associated with the godet 21. 7

FIGURE 3 is a perspective view of a false twister which is used to round and shape the strand.

The starting material for the process of the present invention is a bonded collagen multifilament which will be referred to hereafter ascollagen tape. This material is ribbon-like in form and is made up of from about 20 to about 500 individual collagen'multifilaments. Collagen tape may be prepared by extruding a dispersion of substantially pure swollen tendon collagen fibrils through a multi-orifice spinnerette into an alkaline acetone dehydrat ing bath. The multifilaments, as they emerge from the spin bath, are very loosely united and are approximately circular in cross-section; however, the filaments are drawn from the spin bath by a rotating godet and the tension on the still Wet filaments as they pass over the godet sur- I face bonds the individual filaments together to form a ribbon-like strand. When the bonded multifilament is dried, the ribbon-like shape is retained. it will be understood from the foregoing that the individual filaments are a bonded together by cohesive forces to form the collagen tape.

The mechanical handling of the collagen'tape as it passes through the different tanning solutions and is dried and rounded to form a strand of circular cross-section is best illustrated by FIGURE 1. The machine to be described has been designed for the continuous treatment of collagen tape containing about 195 individual filaments and shaping the tanned multifilament to form a rounded strand about 14.5 mils in diameter, but it will be understood that strands of smalleror larger diameter may be produced by varying the number of individual filaments in the collagen tape and such modifications are well within the scope of this invention.

It will be noted from FIGURE 1 that the collagen tape 11 is transferred from the supply reel 12 to the take-up spool 13 by the driven godets 21, 22 and 23. The tape is stretched between godet21 and godet 22, and is stretched again between godets 22 and 23. Directly below each godet are

auxiliary nylon rollers

31, 32 and 33. The rollers 31 and 32 are surrounded by trays 14 and 15 which may be filled with liquids 41 and 42 that are to be applied to the moving collagen strand. Other means of treating the moving collagen strand with liquids are provided by the

jets

20, 24 and 25.

The tubes'l, 17 and 18 are heated and function to dry and warm the moving strand. The desired circular crosssection of the final product cm be accomplished by means of afalse twister 19 which operates to round and dry the strand as it moves through the drying tubes.17 and 13.

The three godets 21, 22 and 23 may be made of nylon and each is preferably 3 inches in circumference. All three godets are driven by a Reeves variable speed gear reduction motor having an output speed range of 3.3 to 32.1 r.p.m. Directly below godet 21 is an auxiliary nylon roller 31, as best shown in FIGURE 2. The

. separation of the collagen tape on godet 21 is controlled by moving the axis of the auxiliary roller 31 with respect to the axis of the godet. The roller 31 pivots on the hinge pin 26 and may be securely fixed in any position by the set screw 28.

The godet 21 is driven at a speed of about 10 r.p.m. At 10 r.p.m., the linear rate of tanning is about'30 inches per minute. The collagen tape from a tensioning device 35 passes three times around godet 21, the three loops providing sufficient time in the bath 41 to wet out the collagen tape well with the tanning solution.

Godet 22 is driven at 11 r.p.m. and, therefore, produces a 10% stretch in the tape between godet 21 and godet 22. The amount of stretch in this stage may be increased or decreased by varying the relationship between the speeds of godet 21 and godet 22. It will be noted that the strand is wrapped around godet 22 three times. The stretching between godet 21 and godet 22 provides orientation of the drying collagen tape and improves the tensile strength.

Conditions may, for example, be controlled so that the godet 21 is operated at 10 r.p.m., godet 22 is operated at 11 r.p.m., and godet 23 is operated at 12 r.p.m. Under these conditions, one would obtain, in addition to the 10% stretch between godets 21 :and 22, another 10% stretch between godets 22 and 23.. The over-all stretch may be varied from about 10% to and at the present time, the upper limit of stretch appears'to be about 20% The moving collagen tape may be continously treated at godet 21 and godet22. The solution 41 in the tray 14 may be an alkaline aqueous solution of a polyhydric phenol and/or quinone such as: pyrogallol; resorcinol; hydroquinone; 2,24,4' '-tetrahydroxybenzophenone; 1,2-, naphthoquinone; l,2-naphthoquinone-4 sulfonic acid sodium salt; 1,4-naphthoquinone; p-toluqu-inone; 1,2-anthraquinone; or mixtures, of these compounds. Polyhydric phenols and quinones that are most effective in the tanning process of the present invention are those which have an unsubstituted position adjacent to the oxygen function.

" In addition to the polyhydric phenol 'or quinone, the.

solution 41 may contain a small amount (about 0.5%)

of a chelating agent, e.g., the disodium salt of ethylene diamine tetraacetic acid, to associate with any metal contaminants. A strong reducing agent such as formaldehyde 7 can be used in the bath to deter oxidation.

Thetconcentration of polyhydric phenol and/ or quinone in the bath (41) is from about 0.2% to about 2.0% and the preferred polyhydric phenol is pyrogallol. If this bath (41) is acidic or neutral, the collagen tape will pick up too much Water. It'is helpful, therefore, to adjust the pH of this bath to about 7.5-10.5 with an alkali such as ammonium hydroxide or sodium hydroxide. Excellent results have been obtained when the pH of this tanning bath is 8.3.

The collagen tape passes from the tanning bath 41 around the idler pulley 30 and then through the drying tube 16. This drying tube has a cross-sectional area of about 2 to 3 square inches and is about 16 inches in length. Air, heated to about 150 F. is circulated through the tube 16 at the rate of about 600 cubic feet per minute.

The dried collagen tape from the tube 16 passes over an idler pulley 29, is wrapped three times around godet 22, and is wet out in the second tanning bath 42. The, bath 42 contains a basic trivalent chromium salt such as chromium (III) sulfate or chloride, the sulfate beingpreferred. Bath 42 also contains an aldehyde such as: form-w aldehyde, acetaldehyde; furfural; glyoxal; succindialdehyde; inalonic dialdehyde; glutaraldehyde; etc. Formaldehyde is preferred. Bath 42 contains, e.g., an aqueous solution of chromium (III) sulfate and an aldehyde such as formaldehyde or glyoxal, or mixtures of the two. The concentration of chromium as chromic oxide is about 10 grams per liter, the concentration of formaldehyde and/ or glyoxal is about 0.10% to about 0.32% and the pH of the bath is about 2.0-3.5 (unbutfered). If the amount of aldehyde is greater than about 0.32%; the tensile strength of the strand drops and if the amount of aldehyde is less than about 0.05%, the in vivo absorption of the strand will be rapid. In pasing through this bath, the collagen tape absorbs about 1% by weight of chromium as chromic oxide. It has been noted that the optimum wet tensile strength and dry knot strength of the finished strand is obtained when the amount of chromic oxide in the strand to about to F. is circulated through the tube 17 at about 300 cubic feet per minute and air-heated to about F. and then circulated through the tube 18 at about 450-600 cubic feet per minute. 7

- The collagen tape from the bath 42 is rounded and shaped by contact with a false twister 19 of the type illustrated in FIGURE 3. This device automatically im- 7 parts aso-called false twist to the strand, a false twist being a twist whose direction on one side of a point of contact is reversed on the opposite side, thus cancelling the twist. The twisting cycle is most effective when the collagen tape is in the wet state, and this may be controlled by dripping water on the tape from the jet 20. The strand may' alsobe lubricated just prior to contact with the false twister with distilled water which is added through the jet 2 4. When the twist backs up to the pulley 34, as the wet tape emerges from it, a gradual tapering effect of the strand takes place, which rounds it out. The circular shape of thestrand remains after the twist is cancelled. The false twister is operated in the range of .150 to 1000 r.p.m.

on the apparatus illustrated in FIGURE 1.

It is important that the water added through the jet 20 and the velocity and temperature of the air in the drying tubes 17 and 18 be controlled so that the wet tanned tape is sufficiently dry when the strand contacts the false twister 19 to avoid deformation. This results in an improved circular cross-section.

The round collagen strand passes from the false twister 19 around the idler pulley 36 and may contact with a solution from the jet 25 flowing downwardly in a direction opposite to the direction in which the collagen strand is moving. The solution from jet 25 isan aqueous solution of from about 0.08% to about 0.3% formaldehyde adjusted to a pH of about 9. If the concentration of formaldehyde is less than about 0.08% or if the tanning at jet 25 is eliminated entirely, the finished collagen strand will be absorbed more quickly when implanted in body tissues. If the concentration of formaldehyde is greater than about 0.3%, the finished collagen strand will be brittle and have poor dry knot strength.

The wetted out strand from the jet 25 passes through the drying tubes 18 and 17 around the idler pulley 33 and returns through the drying tubes 1'7 and 18 around idler pulley 40. When the godet 23 is operated at 12 r.p.m. to produce about stretch between godet 22 and godet 23, the tension on the finished strand as measured by the tensiometer 44 is about 1500 grams. The dry tanned and rounded strand is removed from the godet 23 by the take-up spool 13 at about 36 inches per minute. The final strand, under the operating conditions described above, has a diameter of about 14.5 mils (sutures size 2/0).

It has been observed that atmospheric humidity, a variable during the spinning of a strand, plays an important part in the stretch and thefinal tensile strength of the strand. The humidity is preferably controlled by encasing the spinning operation within the smallest practical enclosure into which air of controlled humidity may be introduced. Superior uniform strands may be obtained when the relative humidity is maintained at about 40%.

The continuous processing of collagen tape to obtain a unitary strand of outstanding properties will be illustrated by the following examples. By way of contrast, several additional examples are provided to demonstrate that tanning of collagen with individual reagents, namely, a chromium salt, formaldehyde and pyrogallol, results in products having in vivo tensile strength unsatisfactory for a surgical suture. Throughout the speci: fication, all quantities are expressed in parts by weight unless otherwise indicated.

EXAMPLE I A collagen tape approximately 4 mils thick and 60 mils wide containing 192 individual filaments is processed The speed of the godets 21, 22 and 23 is maintained at 10.0, 11.0 and 12.0 r.p.m., respectively. A solution of 0.4 part of pyrogallol, 0.1 part tetrasodiumethylene diaminotetraacetic acid and 99.5 parts of deionized water is adjusted to pH 8.3 with ammonium hydroxide and placed in the tray 14 (bath 41).

A solution of chromium (III) sulfate comprising 0.8 part of chromium as chromic oxide, 0.5 part of lactic acid (85%), 0.24 part of formaldehyde and 98.46 parts of deionized water is adjusted to pH 2.7 with sodium hydroxide and placed in the tray (bath 42).

A solution of 0.16 part of formaldehyde and 99.84 parts of deionized Water is adjusted to pH 9.0 with ammonium hydroxide and placed in a reservoir feeding the passes to the godet 21 and is wrapped three times around the godet and idler 31, thelatter being immersed in the bath 41. It takes approximately fifteen seconds to travel one wrap so that the total exposure to the solution 41 is about 45 seconds. The pyrogallol treated strand then moves into the drying tube. 16 and is subjected to a current of warm air heated to 60 C. The partially dried strand from the tube 16 then passes over the idler pulley 29 and is wrapped three times around godet 22 and auxiliary roller 32. At this time, the moving strand contacts the solution 42 in container 15.

From the solution 42, the strand travels to the top of the drying tube 17 Where it contacts a stream of deionized water dripping from the jet 20. This serves to saturate the strand with water for better bonding during twisting and also helps to remove excess chromium salts. As the strand moves downwardly through the drying tubes 17and 18, it meets a countercurrent stream of .warm air at about. 60 C. and is twisted by the false twister 19, which is rotating at approximately 300 r.p.m. Just before the strand enters the false twister, it is lubricated with deionized water from the jet 24. This prevents abrasion during the untwisting process. The now rounded strand is next washed with the alkaline formaldehyde solution from jet 25 and finally dried by a double passage through the drying tubes 17 and 18. The finished strand is taken up on the godet 23, five to ten wraps being required to prevent slipping, and is stored on the take-up spool 13. In the process described above, about 10% stretch is applied between godets 21 and 22 and another 10% stretch is applied between godet 22 and godet 23. The properties of the product so obtained are summarized in Tables I and II.

EXAMPLE II Solution 41 at godet 21 Parts Resorcinol 0.6 Deionized water 99.4

Mixture adjusted to pH 10.3 with ammonium hydroxide.

Solution 42 at godet 22 Parts Chromium (III) sulfate (as chromic oxide) 0.8

Formaldehyde 0.24 Glyoxal 0.32 Water 99.36

Mixture adjusted to pH 3.5 with sodium hydroxide.

Solution dripped on strand from jet 25 Parts Formaldehyde 0.32 Deionized water -i 99.68

'Mixture adjusted to pH 6.0.

The tape was wrapped six times around godet 21, five times at godet 22 and nine times around godet 23. In all other respects, the conditions of Example 11 were identical with those described in Example I above. The properties of the product so obtained are summarized in Tables I and II.

EXAMPLE III A suture material is prepared exactly as described .in Example II above, except that the solution 41 at godet 21 is a solution of 0.6 part of hydroquinone dissolved in 99.4 parts of deionized Water. The pH of this solution is adjusted to 10.3 with'ammonium hydroxide. The properties of the product so obtained are summarized in Tables I and II.

EXAMPLE 1vv I A strand is prepared by the method described at Ex- 7 ample I. The following solutions are used:

Slution 41 at godet 21 I Water atpH 10.3 (ammonium hydroxide).

Solution 42' at godet 22 V Parts Chromium (HI) sulfate'(chromic oxide) 1.0 Formaldehyde 0.32 Deionized water 98.68

Mixture adjusted to pH 3.5 with sodium hydroxide.

Solution dripped on strand fromj jet 25 Parts Formaldehyde -4. 0.32 Water 99.68

Mixture adjusted to pH 5.6 sodium hydroxide.

The strand so obtained is then immersed for one hour in a solution of 1.0 partp-benzoquinone and 99 parts of distilled water. The strand is rinsed in acetone and airdried. The properties of the product so obtained are summarized in Tables I and 11.

EXAMPLE V Extruded collagen multifilament was tanned in a basic chromium sulfate bath containing 1.25 percent Cr O No formaldehyde or polyhydric phenol was used in the tanning process. Properties of the product are set forth in Tables I and II. p

r EXAMPLE v11 Extruded collagen multifilament was tanned ina bath containing 0.15 percent formaldehyde. No chromium or polyhydric phenol was used in the tanning process. Tables I and II reveal properties 'of the product so'obtained.

TABLE I Tensile Strength (Grams/ Denier) Example Denier Diameter Dry Dry Wet Straight Knot Knot 15. 0 3. 93 2. 00 1. 25 15. 5 3. 16 1. 61 1. 55 15. 6 3. 24 1. 36 1. 39 14. 4 3. 40 1. 61' 1. 48 V 15.3 3.31 1.74 1. 33 VI (only C1) 1,390 2. 6 1. 5 1.2 VII (only ECHO) 1, 440 2. 41 1. 39 0. 98 Catg'ut l, 210 14. 0 3. 60 2. 40 1. 20

TABLE II [In vivo absorptionin pounds] Days Implanted Example 5. 5 3. 2 1. 9 .9 4.5 4.6 '3.6 3.5 0.6 .1 4.8 4.4 3.9 2.9 0.9 .4 4.5 4.6 4.3 4.0 3.9 1.7 V .7 5.6 5.0 3.9 4.3 3.0 0.8 VI (only Cr) .6 1.0 p VII (only ECHO) 4. 0 1. 6 Catgut 8. 2 5. 3 4. 6 3. 9 3. 3 2. 5 1. 4

7 EXAMPLE VIII Another series of experiments was carried out to determine the separate eitects of chromium sulfate, pyrogallol, and formaldehyde'upon an extruded collagen tape. Each reagent was applied' by the procedure described in Example I, above. In experiments 1 through 3, pyrogal- 101 was applied from the bath 41 and distilled water adjusted to pH 3.5 was applied from the bath 42. In experiments 4 through 6, distilled water at pH 8.3 was placed in bath 41 and formaldehyde at pH 3.5 in bath 42. 'In experiments 7 through 9, distilled water at pH 8.3 was placed in bath 41 and chromium sulfate at pH 3.5 in bath 42. In all ten experiments shown below, lactic acid was elminated from bath 42, jets 20 and 24 were not used and the strand was wet out with an aqueous solution of 0.3 percent formaldehyde (pH 8.5) at the jet 25. The following results were obtained:

Experi- Levels of Treatment Bath merit Compound pH Pyrogallol Formaldehyde Chromium sulfate Combination run 1 1 First bath: 1.5% pyrogallol, C12(SO4)s-l-O.3% HCHO, pH 3.5.

Tensile strength pH 8.3; Second bath= 1.0%

Denier et Knot y Straight 1 First bath:1.57 pyrogallol pH 8.3' Second bath-:10? 0r2 s0. 8+0.3% HdHO, pH 3.51 a

In vivo tensile strength Days Sample N o.

2. 08 1. 74 1. 54 I. 66 1.14 1. 90 l. 2. 2 1. 89 1. 96 1. 70 2. 57 2. 1 2. l9 1. 07 2. B6 1; 31 1. 69 2. 12 1.25 4. 59 2. 55 3. 09 2. 21 3. 20 3.84 3. 91 3.10 2. 49 21. 6 2. 81 2. 04 1. 13 1. l8 3. 93 2. 99 3. 1O 1. 97 4. 40 2. 42 2. 56 l. l. 67 6. 66 5. 24 5. 35 4. 65

4 In connection with the data tabulated directly above, it is clear that the in vivo and in vivo tensile strength values for the tanned sample No. 10 are indicative of an excellent material.

EXAMPLE IX Sutures prepared according to the method of the present invention contain polyhydric phenols and/or quinone reduction products that are chemically combined with the collagen. A quantitive determination of the amount of ,polyhydric phenol or quinone that is presentin the finished suture may be made by the following method.

. v A IO-milligram sample of .a polyhydric phenol and/or quinone tanned suture, is placed in a test tube and 1 milliliter of sodium borohydride solution is added- The solution-of sodium borohydride is prepared by dissolving 0.60 gram of sodium borohydride in 20 milliliters of distilled waterand adding one pellet of sodium hydroxide.

This solution is prepared fresh for each group of samples. The test tube containing the suture to be analyzed and borohydride solution is heated over a Bunsen flame until the suture is dissolved. The contents of the test tube are then neutralized with concentrated sulfuric acid and the test tube is heated to decompose any excess sodium borohydride solution. The reaction mixture so obtained is cooled and diluted to 3 milliliters with distilled water. One milliliter of a vanillin reagent, prepared by dissolving 7.5 grams of vanillin in 50 milliliters of ethyl alcohol, is added and the mixture is diluted with 79% sulfuric acid to 23 milliliters. After 20 minutes, the absorbance at 520 mu is compared with a reagent blank using a Beckman D.U. spectrophotometer and four standards containing 0.01, 0.02, 0.03 and 0.04 milliliters of the polyhydric phenol or quinone subject to the analysis, such as a pyrogallol solution, prepared by dissolving 0.130 gram of pyrogallol in 4 N sulfuric acid to a total volume of 100 milliliters.

The absorbance values are plotted against the volume of standard and the percent polyhydric phenol or quinone in the sample is calculated according to the formula K A X 100 Sample weight (mg) Mu 2,2',4,4'-tetrahydroxybenzophenone 520' 1,2-naphthoquinone 570 1,4-naphthoquinne 575 p-Toluquinone 560 1,2-anthraquinone 545 Resorcinol 510 Accurate and reproducible results are obtained with the foregoing procedure with phenols and with quinones, with the exception of benzoquinone. A'separate procedure is followed in determining benzoquinone content of a suture obtained in accordance with this invention. A SOO-milligram sample of a benzoquinone-tanned suture is placed in the test tube. Five (5) milliliters of hydrochloric acid solution (2 N) are added to the tube. The tube and its contents are heated over a Bunsen flame until the suture is dissolved. The contents of the tube are cooled, 5 mls. of ethanol are added thereto, and the resulting solution is shaken. The solution is transferred to a 25 m1. volumetric fiask and is made up to volume with distilled water. The resulting solution is filtered into a 50 ml. beaker. Ten milliliters of the filtrate are added to a 25 ml. volumetric flask, whereupon 1 ml. of pyrogallol solution (1% in water) and 10 ml. of ethanol are added. Distilled water is then added to the 25 ml. level of thefl-ask. After one hour, the absorbance at 425 mu is compared with a reagent blank using the said spectrophotometer and three standards containing 0.01, 0.02 and 0.03 milliliter of a benzoquinone standard solution. The standards are prepared by dissolving 100 milligrams of benzoquinone in 100 milliliters of distilled water.

The absorbance values are plotted against the volume of the standard and the percent benzoquinone in the sample is calculated according to the formula:

Percent benzoquinone:

Density reading at 425 mu Factor Weight of sample (mg) milligrams of benzoquinone Factor: absorben y unit a night.

id 0.92%, and preferably from about 0.30% to about 0.70% polyhydric phenol and/ or quinone as determined by the foregoing analytical methods.

By way of contrast, extruded collagen strand and hide were treated with resorcinol and formaldehyde by the procedures given in the following examples. As shown therein, the products obtained therein contain substantially larger percentages of polyhydric phenol than about 0.25% to about 0.92% characteristic of the sutures of this invention. I

EXAMPLE X Extruded collagen tape (40 grams) was added to a solution containing grams of distilled water, 7 grams of resorcinol, 14 grams of formalin and 5.5 grams of sodium chloride. The pH of the resulting solution was 2.7. The collagen tape was rolled in the solution for 2 hours. The pH of the solution was adjusted to pH 1.5 by slowly adding concentrated sulfuric acid thereto; this was maintained for 3 hours. Additional sulfuric acid was added to bring the pH to 1.0. The collagen tape was rolled in the solution overnight (17 hours). The solution was gradually neutralized with 1.5 grams of sodium acetate and then with 0.75 gram of sodium bicarbonate. The collagen tape was then rolled in the solution, pH 5.5, was washed in tap water for one hour, and was finally dried during a 24-hour interval. The treated collagen tape, on analysis, contains 1.05 percent resorcinol.

EXAMPLE XI The procedure described in Example X, above, was

used in treating 50 grams of wet, fresh, neutral hide. The initial solution contained:

' Grams Distilled water 100 Resorcinol 3.5 Formalin 14 Sodium chloride 2.8

On analysis, it was determined that the/treated hide contains 1.18 percent resorcinol.

EXAMPLE XH Extruded collagen tape (4 grams) and wet, fresh, neutral hide (25 grams) Were tanned concurrently. The tape and hide Were added to a solution of;

The pH of the solution was adjusted to 2.0 with concentrated sulfuric acid. The tape and hide wererolled in the solution for 2 hours. Additional sulfuric acid was added to reduce the pH to 1.5. Again, the tape and hide were rolled for 2 hours, and held in the solution overnight (17 hours). The pH Was adjusted to 1.0 by the addition of sulfuric acid, and the materials were rolled for a 2-hour period. Further adjustment of pH to 0.6 was made with more of the acid. The materials were held in the solution overnight (17 hours). Sodium bicarbonate (l.3 grams) was added slowly to the solu tion, and the tape and hide were rolled in the resulting mixture for 2 hours. The materials were again held overnight. Additional sodium bicarbonate (1.3 grams) was added. The resulting materials were held over- Finally, the tape and hide were washed with distilled water for 3 hours. Upon analysis, it was determined that the resorcinol contents of the tape and hide are, respectively, 1.23% and 1.37%.

It will be understood that the process described above may be utilized in the preservation or" other collagenous materials such as leather, the useful life of which is frequently'shortened by the attack of micro-organisms and enzymes produced by such micro-organisms.

' The method of treating collagen articles with quinones .those skilled in the art that changes and modifications can be made without departing from the spirit or scope of the invention, and it is intended in the appended claims to cover such changes and modifications.

What is claimed is:

1. In a method of tanning collagen that has been acidswollen, extruded and reconstituted; the steps of conphenol is pyrogallol.

3. The method of claim 1 in which said polyhydric phenol is hydroquinone.

4. The method of claim 1 in which said polyhydric phenol is resorcinol.

5. The method of claim 1 in which said aldehyde is formaldehyde.

6. The method of claim 1 in which said aldehyde is glyoxal.

7. The method of claim 1 in the form of a tape.

8. In a method of tanning collagen that has been swollen, extruded and reconstituted; the steps of contacting said. collagen with a solution of a polyhydric phenol selected from the group consisting of monocyclic and dicyclic polyhydric phenols, and subsequently contacting said collagen with a solution of an aldehyde and 'a basic trivalent chromium salt.

9. In a method of tanning collagen that has been swollen, extruded and reconstituted; the steps of contacting saidcollagen with a solution of an aldehyde and a basic trivalent chromium salt, and subsequently contacting said collagen with a solution of a polyhydric phenol selecte'dfrom the group consisting of monocyclic and dicyclic polyhydric phenols.

10. In a method of tanning a collagen suture obtained which the collagen is by extruding and reconstituting acid-swollen collagen; the steps of contacting said suture with an alkaline solution containing pyrogallol and'subsequently contacting said suture with an aqueous solution containing about 0.24 part of formaldehyde, about 0.8 part of chromium III sulfate calculated as chromic oxide, and having a pH of about 2.7. I

11. An aldehyde, phenol and chrometanned collagen article obtained by extruding and reconstituting acidswollen collagen, said article analyzing from about 0.25% to about 0.92% by weight of a polyhydric phenol selected from the group consisting of monocyclic and dicyclic polyhydric phenols, and characterized by a chromiurn analysis from about 0.5% to about 1.5% by weight chromic oxide.

12. An aldehyde, phenol and chrome tanned collagen suture obtained by extruding and reconstituting acidswollen collagen, said suture analyzing from about 0.25 to about 0.92% by weight of pyrogallol, and characterized by a chromium analysis of from 0.5% to about 1.5% by weight chromic oxide.

13. An aldehyde, phenol and chrome tanned collagen suture obtained by extruding and reconstituting acidswollen collagen, said suture analyzing from about 0.25% to about 0.92% by weight of resorcinol, and characterized by a chromium analysis of from 0.5% to about 1.5% by weight chromic oxide.

14. An aldehyde, phenol and chrome tanned collagen suture obtained by extruding and reconstituting acidswollen collagen, said suture analyzing from about 0.25

.to about 0.92% by Weight of hydroquinone, and characterized by a chromium analysis of from 0.5% to about 1.5 by weight chromic oxide.

7 References Cited in the file of this patent UNITED STATES PATENTS OTHER REFERENCES OFlaherty et al.: The Chemistry and Technology of Leather, pages 91-94, 254-255, 261, 267 and 273-275, published 1958 by Reinhold Pub. Co., N.Y.C.

Chen: Syntans and Newer Methods of Tanning, The Chemical Elements, South Lancaster, Mass., 1950, pp. 87-96.

Claims

1. IN A METHOD OF TANNING COLLAGEN THAT HAS BEEN ACIDSWOLLEN, EXTRUDED AND RECONSTITUTED; THE STEPS OF CONTACTING SAID COLLAGEN WITH AT LEAST TWO DIFFERENT SOLUTIONS, ONE OF SAID SOLUTIONS CONTAINING A POLYHDRIC PHENOL SELECTED FROM THE GROUP CONSISTING OF MONOCYCLIC AND DICYCLIC POLYHYDRIC PHENOLS, AND ANOTHER OF SAID SOLUTIONS CONTAINING AN ALDEHYDE AND A BASIC TRIVALENT CHROMIUM SALT.