US2484813A - Spun suture - Google Patents

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US2484813A
US2484813A US597949A US59794945A US2484813A US 2484813 A US2484813 A US 2484813A US 597949 A US597949 A US 597949A US 59794945 A US59794945 A US 59794945A US 2484813 A US2484813 A US 2484813A
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suture
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    • DTEXTILES; PAPER
    • D01NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01FCHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F4/00Monocomponent artificial filaments or the like of proteins; Manufacture thereof

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  • This invention relates to surgical sutures manufactured from animal blood, and preferably from human blood. Sutures of this type have been disclosed in prior applications filed by me, to be more fully identified hereinafter. In general, the present invention is concerned primarily with improvements both in the methods heretofore disclosed, and in the sutures produced thereby.
  • the sutures referred to include at least some constituents of the red blood residue remaining after the extraction of serum or plasma from whole blood, and especially preferred are those made from the entire blood residue remaining after the centrifugal extraction of plasma, as that process is presently performed.
  • the conventional method of extracting plasma removes approximately 54% of the whole blood, leaving a residue which consists primarily of the red blood cells and their content.
  • application 502,503 I describe, inter alia, the use of repeated washings, ether, and dialysis to form a solution comprising disintegrated blood cell material and the liquid content of the cells.
  • application 519,686 I have disclosed a method of doing this by the use of intense cold, so rapidly applied as to explode the cells, so to speak. In either case the result is a solution which is so nearly homogeneous that it will pass unchanged through a Hormann filter (used for removing micro-organisms from plasma), and will not reveal the presence of discrete particles under microscopic examination, even at a magnification of 400 diameters.
  • a mixture of Dry Ice (solid CO2) and kerosene or the like is adequate.
  • the temperature of such a mixture may be adjusted by varying the proportions of its components. Dry Ice sublimes at atmospheric pressure at '78.5 0., which is about 109 F., and melts (under pressure) at 56.6 C. which is about "10 F. Temperatures somewhat higher than that last named may be used, but at substantially higher temperatures, such as 50 F., the desired result is not achieved, even after prolonged freezing.
  • a conventional catgut suture When a conventional catgut suture,
  • the body mobilizes its resources to isolate the suture, and simultaneously it mobilizes an army of leu'cocytes to digest, destroy, and expel the material of the suture.
  • the suture is made from blood, or from red blood residue, in accordance with my discoveries, the body does not act to isolate and cast out the suture material. Instead, the structure of the suture is utilized in the formation of new tisse.
  • the major steps may be outlined as follows.
  • blood taken from a donor in the usual manner is subjected to centrifugal extraction in the conventional way to separate and remove plasma. This step, as noted above, yields approximately 54% plasma and 46% residue.
  • Sterile technique is utilized throughout.
  • the blood is withdrawn directly into the conventional donor bottle, and is centrifuged therein. Precautions are taken at all times to prevent the access of air to the blood being treated.
  • solution produced as above described is colloidal or subcolloidal in form, or it may literally be true that the intense cold referred to breaks down the substances of the cell walls to such a degree as to render them literally and completely soluble in the liquid content of the red blood residue.
  • solution is used in this connection herein, it is intended to refer to the product produced by the deep-freezing technique referred to, or by the etherizing technique referred to, whether the solution be colloidal, subcolloidal, or utterly homogeneous.
  • This solution consists primarily of hemoglobin, electrolytes, and the disintegrated elements of stroma.
  • I shall refer to it as an hemoglobin-electrolyte-stroma solution. It will undoubtedly contain a minor amount of plasma, since the blood cell residue contains a certain amount of this constituent even after centrifugal extraction as above described.
  • the next step is preparation of the material for spinning. This step is largely a matter of establishing a viscosity or texture suitable to the ready formation of a filament upon extrusion. To 70 ,of the process.
  • grams of the hemoglobin-electrolyte-stroma solution I gradually add 55 grams of a 20% solution of sodium sulfide, constantly stirring the mixture with a glass rod. Conveniently, approximately halfsay 30 grams-of the sodium sulfide solution is first added (establishing a ratio of sodium sulfide to blood solution of approximately .6 to 7), and this produces a pronounced thickening. In about three minutes a uniform jelly is produced. This is followed by a step-wise addition of increments of 10 or 15 grams each of NazS solution. Instead of increasing the stiffness of the material, these additional increments tend to reduce its viscosity.
  • the spinning solution now consists of a jellylike material comprising blood solution thickened by the addition of sodium sulfide.
  • This is picked up with a hypodermic syringe of large capacity having a 22 gauge hypodermic needle, and the suture filaments are formed by exerting a uniform pressure on the plunger and extruding the spinning solution into a precipitating medium.
  • a caustic soda bath as the precipitating medium, and to keep the point of the needle below the surface of the bath during extrusion.
  • this bath which I shall call bath No. 1, is a 17.6% solution of sodium hydroxide.
  • it may be contained in a Pyrex trough, say possibly 20 long, 4" or 5" wide and about two inches deep.
  • the spinning solution As the spinning solution is extruded from the point of the syringe, it is set in filamentary form upon contact with the alkaline bath. Quite a number of lengths of filaments may thus be spun, merely by moving the syringe back and forth to form one loop after another. In such manner, I have formed continuous lengths of filament between 200" and 400" long, and comprising ten or a dozen loops.
  • the filaments as so formed are gathered in hanks by their loop ends, and raised out of the setting bath in yarn or thread form. That is,
  • the filaments Upon being withdrawn from bath No. 1, the filaments adhere to one another and begin to consolidate. After holding them in air for several seconds-long enough to drip out excess sodium hydroxide-I immerse the bundle in a setting bath for approximately 30 minutes, and while it is immersed in this bath, stretch it to effect an elongation of at least 20%, maintaining the stretch thereafter. From this point on the strand or filament bundle is so handled as to prevent lengthwise shrinkage.
  • This setting bath which I will refer to as bath No. 2, has the following formula:
  • the suture may desirabl be immersed in a strengthening solution of 2% formaldehyde for a period of from 24 to '72 hours, care being taken, a
  • This final bath is particularly useful as a surface-finishing treatment. Some increase in tensile strength also resultsfrom this final step.
  • sutures of different sizes may be made by using different size needles in the initial spinning step, so as to produce filaments of larger or smaller diameter, or by increasing or diminishing the number of loops formed in the initial setting bath.
  • a suture of any given diameter will be stronger if composed of many fine strands than if made up of relatively few strands of larger diameter.
  • the degree of stretch in the fixing and finishing baths will influence the diameter of the suture.
  • Stretching also influences the tensile strength of the ultimate suture.
  • An increase in the degree of stretch will produce a suture which is stronger per unit of diameter, but which will have a smaller diameter. Accordingly, where a small-diameter suture is desired, it is preferable to proceed as though to make a suture of large diameter and then reduce the diameter by stretching to a higher degree of elongation in the fixing and finishing baths.
  • the strength of the ultimate suture is also influenced by the length of time the suture is permitted to remain in the treating baths which contain formaldehyde. Increasing the concentration of these baths may also increase the tensile strength of the ultimate suture somewhat. It is preferably to use a weaker solution and increase the time of immersion, rather that the converse.- Unfortunately, formaldehyde seems to reduce the flexibility of the ultimate suture.
  • This lubricating effect can be enhanced by admixing the oil with a soft Wax, preferably of animal or vegetable origin.
  • a soft Wax preferably of animal or vegetable origin.
  • the great increase in flexibility which the present process achieves is due, I believe, primarily to utilizing this two-step oil treatment.
  • the sulfonated oil softens the strand, and the unsulfonated oil arrests the softening process, and also lubricates the surface of the suture.
  • the unsulfonated vegetable oil (or oil-plus-wax mixture) is, in other words, a neutral vehiclethat is, it is inert with respect to the suture base.
  • the oils mentioned seem to be best adapted to this work, but apparently any non-drying or semi-drying vegetable oil may be used.
  • I may say that a twentythree filament strand, after a 12 hour air cure, was immersed in sulfonated castor oil for l hours and then in peanut oil (not sulfonated) for 44 hours.
  • This strand after 24 hours of air drying, showed a tensile strength of 42 ozs.more than ample for normal surgical useand yet was abundantly flexible.
  • the sutures After the sutures have been completed, they may, if necessary, be sterilized. Dry heat may conveniently be employed, using the fractional method. In that method the heat is increased, step by step, over a considerable period of time. Other forms of sterilization may be used, such as heating in xylene at F. Lastly, the sutures are tubed in cumene or xylene in the usual way.
  • the suture produced is one in which the strength elements are made from the blood residue remaining after the extraction of serum or plasma from animal blood.
  • the hemoglobin, the electrolytes, and the stroma are all important constituents of the suture.
  • the stroma constituent is largely responsible for the high tensile strength manifested by the completed suture. If the stroma is not reduced to the state of a solution, it will be found that the resulting suture is lacking in tensile strength, and what tensile strength it does possess will not be uniform from end to end of the suture, but will vary considerably from point to point along the length of the suture.
  • the entire process is carried out at temperatures at or below room temperature, except for the final sterilizing step, which may be omitted, if sterile conditions have been maintained, without impairing tensile strength in the least.
  • the reactions which take place involve to a large extent the creation of relatively transitory products, rather than the formation of new compounds from the blood components present.
  • the sodium sulfide added to the original blood solution does not seem to effect any substantial change in the chemical nature of the blood components themselves.
  • sterilization may be omitted if sterile conditions of manufacture are maintained.
  • Conventional sterile techniques such as those employed in removing blood from donors, centrifuging it, etc., will accomplish this, but it is also desirable to provide a sterile atmosphere at the points where the suture is removed from the liquid baths and exposed to the air.
  • the strength of the ultimate suture may be still further increased by twisting the strands forming the initial filament bundle, while they are still soft and cohesive, preferably after removal from bath No. l and before introduction into bath No. 2.
  • twist may be imparted to the filament bundle between bath No. 2 and bath No. 3.
  • a twisted suture is less desirable than one which has not been twisted, because the twisting results in the formation of deep spiral grooves running lengthwise of the suture. Through the tin openings formed by these grooves, after the suture has been implanted, a channel for the entrance of infection may develop.
  • the material of the filaments will, under the stretching imposed, tend to fill in the spiral grooves produced by the twisting, so that the suture, in its final form will be of substan tially uniform diameter throughout its length.
  • Unusually strong sutures may be formed by plaiting or braiding the strands removed from the spinning bath or from bath No. 2, instead of simply twisting them. The remaining steps of the process will consolidate even a plaited suture into a form in which sharply-defined spiral grooves will not be found.
  • a mixture of sulfonated and non-sulfonated oils may be used in softening the suture, prior to treatment with the unsulfonated oil alone. When this is done, the color and clarity of the strand are improved.
  • a mixture of sulfonated oil and xylene may be employed as the softening agent, and this is effective even when it contains as little as 2 /2% of sulfonated oil.
  • Another variation is one which may be made in preparing bath No. 1.
  • Other alkali metal hydroxides may be useful in lieu of sodium hydroxide.
  • Potassium hydroxide seems to be fairly equivalent, for example.
  • ammonium hydroxide cannot be used in equivalent concentrations, and calcium hydroxide is slow in action, possibly because it is difficult to form a sufficiently concentrated solution of this less-soluble alkaline earth.
  • alkaline sulfides having properties similar to the Na2S solution herein described may be substituted therefor, bearing in mind that the proportions must always be adjusted somewhat to secure the best viscosity. If ammonium sulfide is used, for example, it should be used in a rather highly concentrated form.
  • a process for the manufacture of a surgi cal suture from animal blood which process includes extruding a solution of red blood residue into a setting bath and treating the strand so formed with an aldehyde, the step of effecting a controlled increase in the flexibility of the suture by subjecting it, after it has been set, to the ac-* tion of a sulfonated oil, and limiting the extent of such action.
  • the method of producing a suture from a solution of blood residue remaining after centrifugal extraction of plasma from whole blood comprises the steps of thickening the blood solution by the addition of an alkali sulfide in a ratio of approximately 6 parts of alkali sulfide to '70 parts of blood solution, thinning the thickened solution by the addition of increments of alkali sulfide until a suitable spinning viscosity has been attained, and then extruding the solution into an alkaline precipitating me dium.
  • the method of producing a suture from a solution of blood residue remaining after centrifugal extraction of plasma from whole blood comprises the steps of increasing the viscosity of the solution by the addition of a thickening agent, extruding the solution into a precipitating medium so as to form a bundle of precipitated filaments, twisting the bundle of filaments so formed while the filaments are still in a soft and mutually adherent state, and stretching the filament bundle in the presence of a fixing bath to consolidate the bundle of filaments into a unitary strand free of sharplydefined grooves, and thereafter treating the strand so formed so as to cause it to retain the characteristics thus imparted thereto.
  • the method of producing a suture the structural basis of which consists essentially of a consistency of whole blood and a thickening agent, which method comprises: extruding a solution containing at least the elements of stroma and hemoglobin into an alkaline precipitating bath; subjecting the filaments so formed to stretching in an acid setting bath; subjecting the strand so formed to a plasticizing bath containing formaldehyde, glycerine and glue, and further stretching the strand while plastic; setting the strand, and softening the suture so produced.
  • the plasticizing bath consists of glue, formaldehyde solution, glycerine and water, in a ratio of the order of 1:3:4z10.
  • the method of preserving a suture comprising a constituency of blood comprises storing the suture in a tube containing a sterile oil selected from the class which consists of the non-drying and semi-drying oils and mixtures thereof.

Description

Patented Oct. 18, 1949 SPUN SUTURE John 0. Bower, Wyncote, Pa.
No Drawing. Application June 6, 1945, Serial No. 597,949
13 Claims.
This invention relates to surgical sutures manufactured from animal blood, and preferably from human blood. Sutures of this type have been disclosed in prior applications filed by me, to be more fully identified hereinafter. In general, the present invention is concerned primarily with improvements both in the methods heretofore disclosed, and in the sutures produced thereby.
In general, the sutures referred to include at least some constituents of the red blood residue remaining after the extraction of serum or plasma from whole blood, and especially preferred are those made from the entire blood residue remaining after the centrifugal extraction of plasma, as that process is presently performed. The conventional method of extracting plasma removes approximately 54% of the whole blood, leaving a residue which consists primarily of the red blood cells and their content.
My application, Serial No. 502,503, filed September 15, 1943, refers, inter alia, to the production of surgical sutures from blood, and especially from the red cell content of blood. In my application Serial No. 519,686, filed January 25, 1944', an alternative and particularly efiicacious technique is set forth for converting an admixture 01' blood into a solution. The utility of agents such as sodium sulfide in adjusting the viscosity of such a solution so as to facilitate extrusion spinning thereof is also described in that application.
These prior cases are generic in scope, dealing primarily with preparation of a solution from blood and secondarily with various uses to which such solutions may be put. A detailed and comprehensive description of methods for fabricating surgical sutures from such solutions is found in my application 547,317, filed July 29, 1944, now Patent 2,457,804, issued January 4, 1949. The present application represents a still further improvement in the method and in the product produced. Insofar as the subject matter of these prior cases is represented in the present applica tion, the present application is a continuation-inpart of those which have preceded it.
One characteristic of all of the processes disclosed in my prior applications dealing with the formation of a suture from blood is some form of preliminary treatment operative to change the admixture which is blood into a solution. This solution may be colloidal or subcolloidal, but it seems to manifest the characteristics of a true solution. It will readily be understood by those skilled in the art that blood cells themselves, and the material of which they are composed, represent relatively large particles.
In application 502,503 I describe, inter alia, the use of repeated washings, ether, and dialysis to form a solution comprising disintegrated blood cell material and the liquid content of the cells. In application 519,686 I have disclosed a method of doing this by the use of intense cold, so rapidly applied as to explode the cells, so to speak. In either case the result is a solution which is so nearly homogeneous that it will pass unchanged through a Hormann filter (used for removing micro-organisms from plasma), and will not reveal the presence of discrete particles under microscopic examination, even at a magnification of 400 diameters.
Where the solution is formed b the use of intense cold alone, it is important to produce temperatures throughout the blood cell mass of the order of F. and preferably lower, and preferably also in less than 3 minutes. This is a problem of heat transfer, involving the selection of suitable refrigerants in relation to the shape and volume of the containers used, so as to insure the rapid transfer of heat from every portion of the liquid content in the shortest possible time. Where large quantities of material are to be treated, I prefer to use liquid air (dew point circa 183 C. or 29'7 F.) or liquid nitrogen (dew point circa C. or 319 F.), since the extremely low temperatures of these substances will insure a very rapid transfer of heat from the blood residue to the refrigerant. With smaller quantities, or with a cooling surface relatively large in proportion to volume of liquid to be frozen, a mixture of Dry Ice (solid CO2) and kerosene or the like is adequate. The temperature of such a mixture may be adjusted by varying the proportions of its components. Dry Ice sublimes at atmospheric pressure at '78.5 0., which is about 109 F., and melts (under pressure) at 56.6 C. which is about "10 F. Temperatures somewhat higher than that last named may be used, but at substantially higher temperatures, such as 50 F., the desired result is not achieved, even after prolonged freezing.
Surgical sutures produced from the blood solutions of the applications referred to above, and comprising, as their main strength elements, at least one of the major components of normal blood,'are fundamentally different from sutures heretofore known in the art. Surgical sutures heretofore manufactured, either from animal tissues, from animal protein derivatives, or from synthetic resins and the like, are treated by the human body as elements foreign to its own constitution. When a conventional catgut suture,
for example, is implanted in human flesh, the body mobilizes its resources to isolate the suture, and simultaneously it mobilizes an army of leu'cocytes to digest, destroy, and expel the material of the suture. Where the suture is made from blood, or from red blood residue, in accordance with my discoveries, the body does not act to isolate and cast out the suture material. Instead, the structure of the suture is utilized in the formation of new tisse.
I believe that it is important, in furthering this process of utilization and replacement, that the suture itself should contain as few elements foreign to the natural substances of the human body as is possible. Consequently, my efforts have been largely devoted to eliminating the need for including elements which are foreign to the human system.
Referring now to the method which I currently employ for the manufacture of suture materials from blood solutions, the major steps may be outlined as follows. In the first place, blood taken from a donor in the usual manner is subjected to centrifugal extraction in the conventional way to separate and remove plasma. This step, as noted above, yields approximately 54% plasma and 46% residue. Sterile technique is utilized throughout. The blood is withdrawn directly into the conventional donor bottle, and is centrifuged therein. Precautions are taken at all times to prevent the access of air to the blood being treated.
The blood residue remaining after this step of plasma extraction, still in sterile containers, is then subjected to treatment which will reduce the blood cell structure to a state of complete dissolution. I prefer to accomplish this by ultra refrigeration, that is, by the sudden application of intense cold, rather than by the use of chemical reagents. After freezing, the material is permitted to thaw gradually.
It is important that the resulting solution should not contain any fragments of cell structure visible under a laboratory microscope, and that it be entirely homogeneous. ,A solution of this sort is different in kind from that produced by ordinary hemoly sis, in which, although the blood cells are disrupted, yet the resulting fluid none the less plainly reveals under microscopic examination the presence of relatively large particles of stroma, or cell-wall material.
It may be that the solution produced as above described is colloidal or subcolloidal in form, or it may literally be true that the intense cold referred to breaks down the substances of the cell walls to such a degree as to render them literally and completely soluble in the liquid content of the red blood residue. Wherever the term solution is used in this connection herein, it is intended to refer to the product produced by the deep-freezing technique referred to, or by the etherizing technique referred to, whether the solution be colloidal, subcolloidal, or utterly homogeneous.
This solution consists primarily of hemoglobin, electrolytes, and the disintegrated elements of stroma. For convenience, I shall refer to it as an hemoglobin-electrolyte-stroma solution. It will undoubtedly contain a minor amount of plasma, since the blood cell residue contains a certain amount of this constituent even after centrifugal extraction as above described.
The next step is preparation of the material for spinning. This step is largely a matter of establishing a viscosity or texture suitable to the ready formation of a filament upon extrusion. To 70 ,of the process.
grams of the hemoglobin-electrolyte-stroma solution I gradually add 55 grams of a 20% solution of sodium sulfide, constantly stirring the mixture with a glass rod. Conveniently, approximately halfsay 30 grams-of the sodium sulfide solution is first added (establishing a ratio of sodium sulfide to blood solution of approximately .6 to 7), and this produces a pronounced thickening. In about three minutes a uniform jelly is produced. This is followed by a step-wise addition of increments of 10 or 15 grams each of NazS solution. Instead of increasing the stiffness of the material, these additional increments tend to reduce its viscosity. In application 547,317 the addition of 11.6 grams of LePages Liquid Glue to the thickened solution was recommended at this point. I have discovered that the addition of glue to the spinning solution can be eliminated if other and new techniques are employed at later stages This is desirable because glue is a foreign protein, and its presence tends to offset to some extent the non-irritant characteristics of the ultimate suture.
The spinning solution now consists of a jellylike material comprising blood solution thickened by the addition of sodium sulfide. This is picked up with a hypodermic syringe of large capacity having a 22 gauge hypodermic needle, and the suture filaments are formed by exerting a uniform pressure on the plunger and extruding the spinning solution into a precipitating medium. I- prefer to employ a caustic soda bath as the precipitating medium, and to keep the point of the needle below the surface of the bath during extrusion. Preferably this bath, which I shall call bath No. 1, is a 17.6% solution of sodium hydroxide. For convenience, it may be contained in a Pyrex trough, say possibly 20 long, 4" or 5" wide and about two inches deep.
As the spinning solution is extruded from the point of the syringe, it is set in filamentary form upon contact with the alkaline bath. Quite a number of lengths of filaments may thus be spun, merely by moving the syringe back and forth to form one loop after another. In such manner, I have formed continuous lengths of filament between 200" and 400" long, and comprising ten or a dozen loops.
The filaments as so formed are gathered in hanks by their loop ends, and raised out of the setting bath in yarn or thread form. That is,
twenty or more filaments ultimatel form a single suture.
Upon being withdrawn from bath No. 1, the filaments adhere to one another and begin to consolidate. After holding them in air for several seconds-long enough to drip out excess sodium hydroxide-I immerse the bundle in a setting bath for approximately 30 minutes, and while it is immersed in this bath, stretch it to effect an elongation of at least 20%, maintaining the stretch thereafter. From this point on the strand or filament bundle is so handled as to prevent lengthwise shrinkage.
This setting bath, which I will refer to as bath No. 2, has the following formula:
Grams Sulfuric acid (0. P.) 40%- formaldehyde 50 Dextrose 200 Distilled water 670 The evolution of gas usually follows immersion of the strand in this setting bath. The tendency of the strands to adhere to one another and to 3, comprises the following ingredients:
Grams 40% formaldehyde 240 Glycerine 320 LePages Liquid Glue 80 Distilled water 800 The thread, its elongation being maintained by the use of a frame or by applying controlled tension, is immersed in this finishing solution for from to 30 minutes, depending upon the degree of elasticity desired in the completed suture. Further consolidation of the strands into a single filament takes place, with general unifying of the diameter.
The now completed thread is removed, and is permitted to dry for periods varying from 12 to 72 hours, taking steps to prevent linear shrinkage. This drying process seems to have an effect similar to that of curing, as it is known in cloth processing trades. After it is completed, the suture may desirabl be immersed in a strengthening solution of 2% formaldehyde for a period of from 24 to '72 hours, care being taken, a
as before, to prevent shrinkage. This final bath is particularly useful as a surface-finishing treatment. Some increase in tensile strength also resultsfrom this final step.
It will be obvious that sutures of different sizes may be made by using different size needles in the initial spinning step, so as to produce filaments of larger or smaller diameter, or by increasing or diminishing the number of loops formed in the initial setting bath. A suture of any given diameter will be stronger if composed of many fine strands than if made up of relatively few strands of larger diameter. Furthermore, the degree of stretch in the fixing and finishing baths will influence the diameter of the suture.
Stretching also influences the tensile strength of the ultimate suture. An increase in the degree of stretch will produce a suture which is stronger per unit of diameter, but which will have a smaller diameter. Accordingly, where a small-diameter suture is desired, it is preferable to proceed as though to make a suture of large diameter and then reduce the diameter by stretching to a higher degree of elongation in the fixing and finishing baths.
The strength of the ultimate suture is also influenced by the length of time the suture is permitted to remain in the treating baths which contain formaldehyde. Increasing the concentration of these baths may also increase the tensile strength of the ultimate suture somewhat. It is preferably to use a weaker solution and increase the time of immersion, rather that the converse.- Unfortunately, formaldehyde seems to reduce the flexibility of the ultimate suture.
I have found that the effects of the formaldehyde in reducing flexibility, may, to some extent, be counteracted by the following procedure. First, soak the completed suture in a sterile sulfonated vegetable oil, such olive oil, castor oil, peanut oil, or cottonseed oil, for several hours.
Then remove the suture and soak it for several more hours in a similar (i. e. non-volatile) vegetable oil, not sulfonated. The sulfonated oil softens the strand, and, if the thread is permitted to remain in this liquid for too long a time, undesirable changes in its structure, accompanied by a loss of tensile strength, will ensue. Unsuifonated vegetable oils will arrest this softening process and preserve the degree of flexibility established thereby. Moreover, vegetable oils which have not been sulfonated serve as lubricants and thereby greatly facilitate the work of implanting the suture, while at the same time restricting the extent of physical injury done to the tissues which are traversed by the suture. This lubricating effect can be enhanced by admixing the oil with a soft Wax, preferably of animal or vegetable origin. The great increase in flexibility which the present process achieves is due, I believe, primarily to utilizing this two-step oil treatment. The sulfonated oil softens the strand, and the unsulfonated oil arrests the softening process, and also lubricates the surface of the suture. The unsulfonated vegetable oil (or oil-plus-wax mixture) is, in other words, a neutral vehiclethat is, it is inert with respect to the suture base. secondarily, I believe that the elimination of glue from the spinning solution reduces brittleness in the final product. The oils mentioned seem to be best adapted to this work, but apparently any non-drying or semi-drying vegetable oil may be used.
By way of example, I may say that a twentythree filament strand, after a 12 hour air cure, was immersed in sulfonated castor oil for l hours and then in peanut oil (not sulfonated) for 44 hours. This strand, after 24 hours of air drying, showed a tensile strength of 42 ozs.more than ample for normal surgical useand yet was abundantly flexible.
After the sutures have been completed, they may, if necessary, be sterilized. Dry heat may conveniently be employed, using the fractional method. In that method the heat is increased, step by step, over a considerable period of time. Other forms of sterilization may be used, such as heating in xylene at F. Lastly, the sutures are tubed in cumene or xylene in the usual way.
The foregoing description illustrates a preferred process for the production of the sutures of the present invention. It will be seen that the suture produced is one in which the strength elements are made from the blood residue remaining after the extraction of serum or plasma from animal blood. I believe that the hemoglobin, the electrolytes, and the stroma are all important constituents of the suture. I believe that the stroma constituent is largely responsible for the high tensile strength manifested by the completed suture. If the stroma is not reduced to the state of a solution, it will be found that the resulting suture is lacking in tensile strength, and what tensile strength it does possess will not be uniform from end to end of the suture, but will vary considerably from point to point along the length of the suture.
I believe that the presence of the hemoglobin, which constitutes approximately 26.6% of the blood solution before the addition of sodium sulflde, is extremely important in its physiological effects. I believe that this component of the blood residue largely accounts for the fact that the sutures of the present invention will be utilized by the body in the formation of new tissue, and will notbe isolated, destroyed and excreted. The physiological effects of the electrolytes are not clear to me, beyond the fact that the body seems to absorb and utilize the material of the suture somewhat more readily when the electrolytes are present than it does if the electrolytes are removed. These electrolytes consist primarily of the salts of sodium, potassium and magnesium. They are present in the red blood residue in almost twice as high a degree of concentration as they are in whole blood.
I am aware that various proposals have been made for utilizing animal blood in the formation of What have come to be known as plastics. In these processes, the essential character of the blood itself is rather thoroughly destroyed. It serves primarily as a source from which chemical constituents of new materials quite different from blood may be derived. In my process, it has been my aim throughout to preserve the essential character of the constituents of normal blood to as great a degree as possible.
It is to be noted that the entire process is carried out at temperatures at or below room temperature, except for the final sterilizing step, which may be omitted, if sterile conditions have been maintained, without impairing tensile strength in the least. I believe that, because of the moderate temperatures employed, the reactions which take place involve to a large extent the creation of relatively transitory products, rather than the formation of new compounds from the blood components present. For example, the sodium sulfide added to the original blood solution does not seem to effect any substantial change in the chemical nature of the blood components themselves. I believe that the action of the sodium sulfide may be compared to that of surface-active agents, and that in ratios of 3 Na'zS solution or less to 7 of blood solution it acts as a coagulant, and in higher ratios as a dispersing agent. I believe it is almost, if not wholly removed in the solutions of bath N0. 1 and bath No. 2. Certainly the volume of thread leaving the spinning bath is noticeably less than the volume of spinning solution extruded into it.
Similarly, I do not believe that the temperature employed is sufi'icient to effect the formation of any large amount of resin, in spite of the fact that formaldehyde has long been used to form resins with phenols, urea, etc. Some such reaction may occur, indeed, but if so, it is probably only incidental and superficial, and does not convert the entire suture base into a plastic. There are several reasons for believing that the essential character of the blood is not greatl modified by the steps of the process. One of these is the color of the suture, which persists without substantial change, except that a slight darkening, similar to that which follows exposure of normal blood to air for a few hours sometimes occurs. Another and very compellin reason is that the body reaction to the presence of these filamented sutures is almost negligible and is difi'erent in kind from that which results from the presence of any other type of suture, as is substantiated by repeated experiments. That is, the body gradually utilizes the structure of my sutures in the formation of new tissue, and does not mobilize its pathogenic resources to isolate and destroy them.
Using a number of rabbits as subjects, a different suture has been implanted beneath the peritoneal coating of the stomach of each. The animals have been sacrificed after a given interval-say 30 days-and sections have been taken to show a portion of the suture in each subject. Under microscopic examination it is invariably seen that animal tissue sutures impregnated with blood solution according to my previous applications, and sutures made in accordance with the present disclosure, have been well received by the body, and have begun to be utilized in the creation of new tissue which replaces the suture material. Other sutures, e. g., catgut, either plain or chromicized, are not well received, but are isolated, digested and thrown off, leaving a tubular defect lined with scar tissue. I have on occasion used a single subject and have used a different suture material for each of several stitches. The reaction of the body to the respective types of suture materials has been the same as where different subjects have been used.
From this it seems evident that the process herein disclosed does not impair or destroy the essential character of Whatever components of the blood may be responsible for this new body tolerance, since the body reaction to sutures formed entirely of blood in accordance with the present disclosure is even more favorable than the reaction to sutures made with catgut and impregnated with a blood solution which has been ultra-refrigerated and thawed; and is fundamentally and profoundly difierent from the bodily reaction to sutures of the prior art.
The process as outlined above is purely illustrative. Many variations in detail have been used, and many more will suggest themselves to persons skilled in the making of synthetic fibers.
It has been suggested, for instance, that sterilization may be omitted if sterile conditions of manufacture are maintained. Conventional sterile techniques, such as those employed in removing blood from donors, centrifuging it, etc., will accomplish this, but it is also desirable to provide a sterile atmosphere at the points where the suture is removed from the liquid baths and exposed to the air.
I have discovered that the strength of the ultimate suture may be still further increased by twisting the strands forming the initial filament bundle, while they are still soft and cohesive, preferably after removal from bath No. l and before introduction into bath No. 2. Alternatively, twist may be imparted to the filament bundle between bath No. 2 and bath No. 3. Ordinarily a twisted suture is less desirable than one which has not been twisted, because the twisting results in the formation of deep spiral grooves running lengthwise of the suture. Through the tin openings formed by these grooves, after the suture has been implanted, a channel for the entrance of infection may develop. However, where the filament bundle is twisted before the strand has been finally consolidated, in accordance with my invention, the material of the filaments will, under the stretching imposed, tend to fill in the spiral grooves produced by the twisting, so that the suture, in its final form will be of substan tially uniform diameter throughout its length. Unusually strong sutures may be formed by plaiting or braiding the strands removed from the spinning bath or from bath No. 2, instead of simply twisting them. The remaining steps of the process will consolidate even a plaited suture into a form in which sharply-defined spiral grooves will not be found.
Some of the other phases of the process which may be modified if desired, should be noted. Within reasonable limits, it is possible to vary the proportions of ingredients of bath No. 2 and bath No. 3, or even to combine these baths in such a way as to secure their several results in a single step.
Although tubing the completed suture in xylene I or cumene has been suggested, I have discovered that the suture does not deteriorate if tubed dry. However, where the suture has been tubed dry and stored for a long interval it loses something of that flexibility which I regard as being of the greatest importance. I have discovered that this flexibility will be maintained if the suture be stored in sterile oils, particularly vegetable oils of the non-drying or semi-drying type, and especially peanut oil or olive oil. These also act as preservatives, yet do not detrimentally affect the suture material nor impair its non-irritant characteristics. Johnson's Baby Oil, which seems to be an emulsion incorporating a mineral oil component, has proved very satisfactory. My work in this connection has been so recently completed, that I am not able at this time to say whether hydrocarbons such as xylene may in every case be replaced by sterile oils such as those named. So far as my present knowledge goes, this seems to be the case.
A mixture of sulfonated and non-sulfonated oils may be used in softening the suture, prior to treatment with the unsulfonated oil alone. When this is done, the color and clarity of the strand are improved. Alternatively, a mixture of sulfonated oil and xylene may be employed as the softening agent, and this is effective even when it contains as little as 2 /2% of sulfonated oil.
It will be noted that in carrying out the preferred process discussed above, I use the blood residue remaining after plasma extraction. The whole blood may be used with comparable results, and is so used for preference when the final sterilization is to be omitted. An advantage gained is that an operation involving handling of the material is eliminated, and the risk of contamination is proportionately reduced. On the other hand, it is somewhat more costly, since much energy is wasted in freezing plasma which is neither improved nor degraded by that step.
Another variation is one which may be made in preparing bath No. 1. Other alkali metal hydroxides may be useful in lieu of sodium hydroxide. Potassium hydroxide seems to be fairly equivalent, for example. On the other hand, ammonium hydroxide cannot be used in equivalent concentrations, and calcium hydroxide is slow in action, possibly because it is difficult to form a sufficiently concentrated solution of this less-soluble alkaline earth.
Similarly, alkaline sulfides having properties similar to the Na2S solution herein described may be substituted therefor, bearing in mind that the proportions must always be adjusted somewhat to secure the best viscosity. If ammonium sulfide is used, for example, it should be used in a rather highly concentrated form.
It must be remembered that blood varies widely in its composition, depending not only on the source, but also on varying physical condition in a single source. The ratio of red cells to White, and of total cells to total liquid is seldom constant in any man or animal. It is an advantage of the present invention that the various baths are operative in spite of considerable variation in the composition of the blood, and, as a corollary, that the composition of these baths may be varied within fairly wide limits to secure optimum re- 10 sults from any particular batch of raw material.
I claim:
1. In a process for the manufacture of a surgi cal suture from animal blood, which process includes extruding a solution of red blood residue into a setting bath and treating the strand so formed with an aldehyde, the step of effecting a controlled increase in the flexibility of the suture by subjecting it, after it has been set, to the ac-* tion of a sulfonated oil, and limiting the extent of such action.
2. The process of claim 1 in which the exent of increase in flexibility is controlled by employing an admixture of sulfonated oil with a vehicle which is inert with respect to the suture base, and adjusting the proportion of sulfonated oil to that required to produce the degree of flexibility desired.
3. The process of claim 1 in which the extent of increase in flexibility is controlled by applying a non-sulfonated oil or neutral hydrocarbon to the suture when the desired degree of flexibility has been attained.
4. The method of flexibilizing a suture spun from a solution of animal blood, which method comprises the step of soaking the suture in a sul-= fonated oil for a period of from 15 minutes to 8 hours, followed by thefurther step of immersing the suture in a non-volatile vegetable oil not sulfonated to arrest the action of the sulfonated oil and preserve the degree of flexibility attained in the preceding step.
5. The method of claim 4 in which the sulfonated oil is a vegetable oil.
6. The method of producing a suture from a solution of blood residue remaining after centrifugal extraction of plasma from whole blood, which method comprises the steps of thickening the blood solution by the addition of an alkali sulfide in a ratio of approximately 6 parts of alkali sulfide to '70 parts of blood solution, thinning the thickened solution by the addition of increments of alkali sulfide until a suitable spinning viscosity has been attained, and then extruding the solution into an alkaline precipitating me dium.
'7. The method of producing a suture from a solution of blood residue remaining after centrifugal extraction of plasma from whole blood, which method comprises the steps of increasing the viscosity of the solution by the addition of a thickening agent, extruding the solution into a precipitating medium so as to form a bundle of precipitated filaments, twisting the bundle of filaments so formed while the filaments are still in a soft and mutually adherent state, and stretching the filament bundle in the presence of a fixing bath to consolidate the bundle of filaments into a unitary strand free of sharplydefined grooves, and thereafter treating the strand so formed so as to cause it to retain the characteristics thus imparted thereto.
8. The method of producing a suture the structural basis of which consists essentially of a consistency of whole blood and a thickening agent, which method comprises: extruding a solution containing at least the elements of stroma and hemoglobin into an alkaline precipitating bath; subjecting the filaments so formed to stretching in an acid setting bath; subjecting the strand so formed to a plasticizing bath containing formaldehyde, glycerine and glue, and further stretching the strand while plastic; setting the strand, and softening the suture so produced.
9. The method of claim 8, in which the amount 11 .of formaldehyde in the plasticizing bath is equal to approximately one-third of the amount of glycerine.
10. The method of claim 8, in which the ratio of glue to formaldehyde solution to glycerine in the plasticizing bath is of the order .of 1:3:4.
11. The method of claim 8, in which the plasticizing bath consists of glue, formaldehyde solution, glycerine and water, in a ratio of the order of 1:3:4z10.
12. The method of preserving a suture comprising a constituency of blood, which method comprises storing the suture in a tube containing a sterile oil selected from the class which consists of the non-drying and semi-drying oils and mixtures thereof.
13. The method of preserving a suture comprising a constituency of blood, which method comprises storing the suture in a tube containing a non-drying sterile vegetable oil.
JOHN O. BOW ER.
REFERENCES CITED The following references are of record in the file of this patent:
12 UNITED STATES PATENTS Number Name Date 505,148 Weaver Sept. 19, 1893 1,168,174 Davis Jan. 11, 1916 1,999,641 Sharp Apr. 30, 1935 2,280,603 Plambeck Apr. 21, 1942 2,298,424 Schreiber Oct. 13, 1942 2,339,562 Eustis Jan. 18, 1944 FOREIGN PATENTS Number Country Date 26,155 Great Britain 1908 165,832 Great Britain July 11, 1921 455,899 Germany Feb. 11, 1928 OTHER REFERENCES Technology of Cellulose Ethers, by Worden, published in 1933 by Worden Laboratory and Library, Millburn, New Jersey, pages 696 and 2175.
Page 210 .of Rideal, Disinfection and Disinfectants, Second edition, published in 1898 by The Sanitary Publishing Co., Ltd., 5 Fetter Lane, Fleet Street, London, England. (Available in Div. of Patent Ofilce.)
Article, Fatty Alcohols and Their Sulphonated Products, page 999 of The Melliland Textile Monthly for March 1932'. (This article is avail able in Div. 55 of U. S. Patent Oflice.)
US597949A 1945-06-06 1945-06-06 Spun suture Expired - Lifetime US2484813A (en)

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US5891167A (en) * 1996-06-19 1999-04-06 United States Surgical Corporation Collagen coated gut suture
US5954748A (en) * 1996-07-15 1999-09-21 United States Surgical Corporation Gelatin coated gut suture
US20020193829A1 (en) * 2001-03-26 2002-12-19 Tyco Healthcare Group Lp Oil coated sutures
US7972376B1 (en) 2007-12-21 2011-07-05 Edwards Lifesciences Corporation Capping bioprosthetic tissue to reduce calcification
US8007992B2 (en) 2006-10-27 2011-08-30 Edwards Lifesciences Corporation Method of treating glutaraldehyde-fixed pericardial tissue with a non-aqueous mixture of glycerol and a C1-C3 alcohol
US8236241B2 (en) 1998-09-21 2012-08-07 Edwards Lifesciences Corporation Treating biological tissues to mitigate post-implantation calcification
US8632608B2 (en) 2002-01-03 2014-01-21 Edwards Lifesciences Corporation Treatment of bioprosthetic tissues to mitigate post implantation calcification
US8846390B2 (en) 2010-03-23 2014-09-30 Edwards Lifesciences Corporation Methods of conditioning sheet bioprosthetic tissue
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US20020193829A1 (en) * 2001-03-26 2002-12-19 Tyco Healthcare Group Lp Oil coated sutures
US20070265660A1 (en) * 2001-03-26 2007-11-15 Kennedy John J Oil coated sutures
US8632608B2 (en) 2002-01-03 2014-01-21 Edwards Lifesciences Corporation Treatment of bioprosthetic tissues to mitigate post implantation calcification
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