DE1469075B - Process for the production of twisted collagen thread - Google Patents

Description

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Essentially pure swollen collagen fibrils The collagen dispersion can be either vertical or through a slot nozzle into an alkaline precipitation bath, where it is extruded horizontally. In the present case characterized in that one becomes one of one with the aid of the extrusion process flowing acetone-ammonia mixture existing in a horizontally operating extrusion machine Dehydration bath extruded and the resulting 5 described according to the drawing.

Strips or bands individually or several together The machine described is intended for continuous

twists, stretches and dries in the usual way. Extrusion of a tape from an aqueous dis-

According to the method according to the invention, the persion with about 1% pure swollen KoUagen made sterile surgical sutures have a. fibrils determined. The dehydrated tape is about

exceptional strength. io 0.064 mm (64 µ) thick and about 12.7 mm wide; it is

The raw starting material used in the manufacture of but of course that changes are made

extruded collagen sutures according to which can be used to make tapes of various sizes

drive the invention consists of a dispersion of produce.

swollen collagen fibers, which consist of different The collagen dispersion is through a narrow

Animal species or from different tissues individual 15 slot in a circulated dehydration.

Species originate. These collagen fibrils are made of an acetone-ammonia mixture

characterized as having a uniform cross-section, pressed. The tape is at the top with the HMe

have a periodic cross bond that is pulled per unit rollers 101 and 102 from the bath and between

is about 640 angstrom units, and the capabilities of rollers 101 and 102 and rollers 103 and 104

Possess, reversibly stretched in aqueous acidic solutions 20. Provision has been made so that this

to swell. The KoTBrgenfaserchen from the Ochsenwegende belt after leaving the rollers 101 and

Femoral tendons are preferred for this procedure. 102 treated continuously with a liquid

In the preparation of a dispersion it can be swollen. The rollers 105 and 106 give the

For collagen fibrils it is important for the extrusion, tape an additional stretch and alignment,

that the removal of in the mammalian tendon in natural ² 5 According to the drawing, the dehydration flows

Lich state contained impurities and the bath in the container 122 at one end to and at the

Separation of the collagen fibrils to form an extrusion port through the container 122

homogeneous dispersion is effected under conditions concurrent with the extruded collagen 123. The

which dissolves or decomposes collagen.

avoid. The tensile strength of the extruded bath product is around 850 ccm / min, but it can be higher

is increased from maintaining the original collagen than 1200 cc / min. A circulation

fiber structure dependent. speed of about 850 cc / min leads to

During the extrusion process, the homogeneous a rapid change of the bath and the flow

Dispersion of swollen collagen fibers by speed is used to make the freshly extruded tape

a slot in an acetone-ammonia mixture extru- 35 to lead away from the extrusion opening. One

diert, which guides the individual collagen fibers at a circulation rate of 50 ccm / min.

Direction parallel to the surface of the extruded strip. but to a satisfactory change of the spinning bath,

the aligns. The ultimate strength of a collagen band Circulation speeds of over about 1200 ecm /

depends on the side bonds between min cause breaking of the extruded tape,

the collagen fibers. Thus, a parallel exit 4 ° The extrusion opening 124 consists of one

direction of the individual fibrils to a maximum slit about 1.27 cm long and 0.64 mm wide in

Number of side ties and to a maximum of a brass plate about 3.18 cm in diameter

Tear resistance. and 0.64 cm thick. Such an extrusion opening

The extruded tape is produced for further alignment a dehydrated tape about 64 μ thick

of collagen fibers stretched, further twisted and 45 and about 1.3 mm wide. A larger extrusion

dried. The size of the tape used and the opening (approximately 2.54 cm in length and 1.14 mm in width)

The number of ribbons that are twisted together creates a ribbon approximately 2.54mm x 114μ, which is used for

determine the diameter of the end product. On the creation of a sewing thread of size 2/0 (thread

In this way, the present method is particularly suitable for a cross-section of about 0.38 mm) can be twisted.

Production of sewing threads of various sizes, 5 ° The extruded collagen is

especially suitable for thicker sewing threads. driven rollers 101 and 102, 103 and 104 and 105

The invention is continued in detail in FIGS. 16 and 106 below. The lower rollers 101,103 and connection with a drawing, which represents a 105 expediently made of polyamide and the upper schematic view of a machine for rollers 102, 104 and 106 made of hard rubber. Each whale making a continuous collagen ribbon 55 zenpaar is driven together so that the upper one is used by extrusion. and lower rollers at the same speed

The raw material for the products of the invention is running.

is the collagen fiber that is produced from mammalian tendons when spinning at a speed of

is obtained. Whales are an important source of about 2.97 ecm of a 1% collagen dispersion per

Collagen, and the Walsehnenkollagen provides a loading ^6o minutes, the rollers 101 and 102 with a total

A satisfactory starting material. Pig and sheep speed of about 10 rpm. at

and ox tendon are also suitable for this. The best 10 rpm is the linear speed of the

Results are approximately 76.2 cm / min using the lower spinning. The rollers 103 and 104

Cattle flexor tendon preserved. are driven at 14 rpm, and there all the rollers

The source solution may be sawn from an aqueous solution ⁶ 5 have the same extent (about 2.54 cm by standing, from about 0.2% to about 1.0% cyanoacetic diameter), a 4O ° / contains cent, stretching in the band between . The appropriate pH of the swelling solution is 2 to 3 for rollers 101 and 102 and rollers 103 and 104. The degree of stretch at this stage can be

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filtered by varying the ratio between the Ge diatomaceous earth filters. This kieselguhr filter is a

speeds of the driven rollers 101 and 103 inert analytical filter material. That in general

can be increased or decreased. The stretching between the slightly acidic filtrate is adjusted to a pH of 7 with a few drops

sch η the rollers 101 and 102 and the rollers 103 and fen dilute sodium hydroxide set. then

104 leads to alignment of the drying belt 5, the neutral enzyme solution becomes distilled water

and improves tear resistance. added to bring the total volume to 1200 parts

The extrusion conditions can e.g. B. so bring. 400 parts of the cut tendon are cut into

be adjusted so that the roller 101 is immersed at 10 rpm, this solution, which is then treated with a toluene

the roller 103 with 14 rev / min and the roller 105 with a layer to prevent the formation of mold

15 rpm. Under these conditions io is covered. This tendon-enzyme mixture is used at

is obtained in addition to the 40% elongation between 37.5 ° C overnight (15 to 20 hours) in the incubator.

the rollers 101 and 102 and the rollers 103 and 104 hold.

another 10% stretch between the rollers. After the incubator treatment, the tendons are

103 and 104 and rollers 105 and 106. The slices three or four times by decanting with

velvet stretching can be varied from about 20 to 15 times of distilled water and then washed with lOOO

50% and z. Currently, the upper limit of the stretching is len water with 4 g of ethylenediaminetetra-sodium tetra-

at about 58%. acetate treated. The tendon and salt mixture will

The moving belt may be continuously overall almost 2 hours at 37.5 ⁰ C to remove soluble washing and / or 107 proteins, and lipids are tanned kept in the incubator in the containers. After this and 108, or a two-stage tanning by 20 water treatment, the pH is adjusted again, if necessary, treatment of the tape when leaving the roller 101 to 7, since the tendon disks are easier in new and then again when leaving the roller 103 a transparent state (less swelling and hydration). The drawing illustrates a procedure to be dealt with. The tendon disks are again brought into contact with a continuously moving band with a washing solution in the container 107 after being washed with the distilled water by decanting with five to six alternations. The moistened belt returns from a The swelling solution is a 50% aqueous methanol-free rotatable, non-driven roller 132 solution, which is based on about 0.35% perfluorobutyric acid and touches the tanning bath 108 in a second stage. based on total solvent weight. In the all-in its moist state, the tanned tape is mean, the collagen dispersion is easy to handle with about an additional time due to the faster rotating 30 l% solids concentration and rollers 105 and 106 are stretched by 10%. The amount of acid swelling solution can easily be calculated from the tension of the tape using hot air nozzles 133 weight and the solids content of the tendons used and 134th . The acidic solution is through

A suitable tanning bath 109 is prepared by mixing 6000 parts of methanol with 3.987 parts

Addition of 4 ml of a 40% strength aqueous formaldehyde 35 distilled water produced. This aqueous metha-

solution and 1 g of aluminum ammonium sulfate to 1 linol mixture are added 42 parts of perfluorobutyric acid

ter water. The Alunümumammoniumsulfat acts as sets.

Buffer and creates a pH of about 4.2. 2 liters of the acidic aqueous methanol solution is on under

The tanning solution tans almost 300 m of the tape. 25 ⁰ C cooled, in a dispersing vessel of ge

It must be noted that, although of sufficient horizontal 40 capacity and handled

The extrusion process described in the valley is mixed with slices of collagen while stirring

the same principles were added to the dispersing kettle at a slight decrease - about 60 rpm. It is

Change for a vertical down or vertical up- important that the remaining stages of the process

Windwärts performed extrusion advertising applied at temperatures below 25 ⁰ C are performed

the can. 45 and that the temperature of the collagen dispersion is this

Extruding a dispersion of swollen limit does not exceed.

Collagen fibers to produce a uniform. Stirring is continued for 3 hours while-

Strand with excellent properties will swell in the end of the individual collagen slices.

the following examples. In the description, the dispersion is then repeated by

Exercise, all amounts are given in parts by weight, 50 press through a running stainless steel measuring pump

unless otherwise stated. Steel and through series-connected nozzles made of rustproof

_. . - free steel with openings of 0.76 and 1.02 mm

^Beis P ^everal homogenized.

1. Preparation of a collagen dispersion _D j _e dispersion is, as described below,

The cattle lower flexor tendon is extruded to form collagen bands.

of fat, non-collagenous protein and others _ “. , _T. ",.

Foreign substances cleaned and spinning the collagen ^{dispersion on an electric 2 ".}

Meat cutting machine with rotating knife in the above-described collagen dispersion is 4 hours

cut frozen state. The tendon sections are vented under vacuum for 31 hours at 25 ° C and

are aged perpendicular to their longitudinal axis to a thickness of 60 for 16 hours at 5 ° C and then in the horizontal

cut from about 0.38 to 0.64 mn \ . working extrusion machine according to the drawing

The cut tendon is then enzymatically immersed in an acetone ammonia dehydration bath

solution treated to dissolve the elastin. The extrudes that continuously through the container 122

Enzyme solution is made by stirring for 10 minutes at a rate of about 900 ml / min.

40 parts of malt diastase with 400 parts of water is produced. At this stage of the process, the ammo

represents. The homogeneous dispersion is 20 minutes with niac content of the dehydration bath to 138 mg / Li-

Centrifuged 2000 rpm and the clear aqueous solution ter and the water content kept at 53 g / liter,

from the centrifugation stage in vacuum through a speed of rollers 101 and 102, 103

and 104 as well as 105 and 106 becomes 10.0; Held at 13.5 and 14 rpm. The tape is continuously washed in container 107 and tanned in bath 109 , which consists of an aqueous solution of 4 ml of 40% aqueous formaldehyde and 1 g of aluminum ammonium sulfate per liter. The relative humidity is maintained at 26% during the extrusion. Blowers 133 and 134 are operated so that the tension on the take-up roll is about 175 to 180 grams. A number of the ribbons thus obtained are moistened and twisted together and dried under tension to form a sewing thread.

If the suture thread thus obtained is diluted in a mixer with an excess of Bringing aqueous acidic solution and stirring vigorously, the sewing thread turns into a dispersion of swollen Collagen fibers that have the shape and shape as they were in the original collagen dispersion are present prior to extrusion.

3. A piece of the dried and tanned tape according to Example 1 (64 * ji thickness and 1.3 mm width) is made y 1 to 3 minutes in an aqueous solution of 10 g of dextran sulfate (sulfate of a grape sugar polymer) per liter immersed. Other polysaccharides can also be used as binders alone or in combination be used with dextran sulfate.

The moistened tape is twisted under tension (about 5 twists per 2.54 cm length) and allowed to dry at room temperature under tension with a weight of about 136 to 227 g. The relative humidity during this drying step is maintained at about 50 ° / ₀ . Under these conditions, the twisted tape will stretch to a length of about 10% more than the original length of the dried tape. When the twisted tape has dried thoroughly (about 15 hours), the strand can be polished in a grinding device to a thread cross-section of about 0.17 mm (size 5/0).

The sewing thread size 2/0 (thread cross-section approx. 0.38 mm) can be made by twisting 5 ribbons together 64 μ thick and 1.3 mm wide can be achieved using dextran sulfate solution as prescribed ) have been moistened. The tension applied to the twisted ribbon (approximately 4 twists in 2.54 cm Length) during drying is about 1135 g.

Plasticizers such as diethylene glycol, crosslinking agents such as the acetal condensation product can be used according to US Pat. No. 2,786,081 and tanning agents such as chromium compounds in the strip treatment bath added before the twisting process. The twisted strand is in the after polishing Grinding device round and flexible and has tear resistance properties that meet the requirements of the Pharmacopeia of the United States, Volume XV, p. 708.

4. Any samples from different sections of the continuous, from a single one

ίο Cut out the strand made of the ribbon and ground to a circumference of 5/0 (thread cross-section 0.17 mm) as described in Example 3. Each sample is five feet long. These samples are packed in tubes made of a trifluorochloroethylene polymer with 90% isopropyl alcohol and 10% by volume of water and the samples are _{sterilized by means of electron beams (3 · 10 6} RAD). The RAD unit is the unit of measurement of the radiation absorbed and is equal to 100 ergs / g. The average dry tensile strength of these

ao any sample is 907 g. The average dry knot strength is 580 g. The average Wet knot strength is 431 g.

According to the method described above, absorbable sutures are obtained which are better than those from Sewing thread made from casings, both in terms of strength and evenness. The sutures according to the method of the present invention retain more than half their strength (tear resistance) up to 6 or 7 days after implantation in the animal body. the The rate of dissolution in animal tissues is of course dependent on the degree of tanning. Chrome-tanned strands retain more than half their tear strength for about 15 days after implantation in the carcass.

The collagen band, which, as stated, is twisted to form the strand, is itself made of collagen fibers composed, which are rectilinear and aligned in a direction parallel to the longitudinal

axis of the belt runs. The 640 angstrom distance, which is characteristic of the collagen fibers in their original condition, can be easily distinguished by examining the collagen ligaments or strands in the electron microscope. This is important for noting that di & collagen fibrils not any morphological change throughout the process of the present invention have suffered.

1 sheet of drawings

209 535/519

Claims (1)

1 2 collagen instruments, tennis rackets, etc. known, which is characterized in that animal Tendons are advantageously frayed while keeping the temperature cool, that Process for the production of twisted collagen fiber material by incorporating acids and threads, in particular for use as surgical 5, if necessary, water with thorough mixing on gisches suture material, by extruding from pH values of about 2.5 to 4.5, preferably about 3 , 5, animal tendons obtained in the usual way, the evenly swollen mass, homogenized dispersions of essentially no more after homogenization and incorporation of pure swollen collagen fibrils through a water, in more or less wide ribbons transferred-slot nozzle into an alkaline precipitation bath, thereby io and these are twisted into threads. Characterized at the outset that one from a product for the manufacture of the threads are made of the flowing acetone-ammonia mixture - cast collagen fiber slurry, which are extruded into strips of the dehydration bath and which are cut and twisted into threads without holding strips or ¹ single or multiple straps, the mass is previously twisted, stretched and subjected to dehydration treatment in a certain coagulation and together in the usual way. It dries. Threads produced in this way are very unsatisfactory in terms of their tensile strength and are very unsuitable for - use in surgery. The German patent specification 842 825 describes an ao process for the production of artificial structures, The invention relates to a method of manufacturing such as threads, hoses or films, from homogeneous, a string-like material made of animal tendons, gel-like, water-containing dispersions of animal _ such as absorbable sutures and ligatures for surgical, skin and tendon collagen, which is characterized by gical purposes. net is that one animal collagen material, which To explain the invention, the following no or only slight chemical pretreatment is carried out. The terms used are defined as follows: drive has, shredded or fiberized, the received The expression "swollen collagen fiber" is a mass with the addition of known chemicals, in particular means a thread-like collagen structure, which in acidic special acids, by swelling in an aqueous one Solution homogeneously distributed over a cross-section of about 5000 to about medium, possibly the swollen 90,000 angstrom units is swollen. 30 lene mass by means of sieving, rolling, pressing, stirring The term "band" used here denotes, etc., further refined mechanically, with the a long thin flat strip of aligned- avoiding thermal damage to the material th collagen fibrils. all operations at temperatures below 40 ⁰ C, The term "strand" denotes one or preferably kept below 25 °, and this dispersion several ribbons that are twisted together and then deformed into a shape. Here, too, coagulation or formation of a uniform structure of circular a special, the tensile strength of the end product Cross-section were united. treatment that does not have any significant influence At the moment, practically the entire production is planned. absorbable sutures or ligatures from sheep- Finally from the German patent specification or ox intestine produced by a process, 40 685 685 a process for the production of webs, which is time consuming and costly. This process weaves and other textiles by spinning, the manufacture of a uniform product does not involve weaving or other processing of skin fibers, suitable. The percentage of production resulting from the coarse fiberization of swelling agents of defects such as insufficient tear resistance and treated skin, treatment of the coarse fiber material lack of uniformity is useless is great. 45 with changing the colloidal properties of the fibers- The starting material, i.e. H. Sheep intestines, is only in the, especially adhesions and cornifications limited quantities available and you can use the water deprivation preventive agents such. B. Do not predict the thickness of the end product. with water-miscible organic liquids Major drawbacks are also known to the best that have been obtained from gut and fine fiberization manufactured sewing threads available. The individual 5 ° is characterized in that the coarse fiberization Threads vary greatly in cross-section, and the length by pressing out the swollen, known per se such a thread is due to the length of the skin or the skin fiber material obtained from it then worked limited. Furthermore by long, gradually tapering pipes or an intestinal thread becomes brittle and its pliable nozzle occurs, and that the strands obtained in this way, strength and strength decrease with aging when 55 threads or ribbons are immediately Fats and other impurities while avoiding air drying with the colloidal properties processing have not been completely removed. treated shafts of the fibers modifying agents In view of these obvious disadvantages, i. that is, the threads running out of the press are surgical catgut and the disadvantages of currently being tanned in a tanning bath, The manufacturing processes used were many 60 The threads manufactured in this way also have no Attempts have been made to obtain strength from other collagen-rich so that they can be used in particular as chi- well to make a better product. Collagen is surgical sewing material that cannot be used present in all connective tissues and can be in planar. Quemer way obtained from skins and sinews, the subject matter of the invention is therefore a method for will. 65 Production of twisted collagen threads, in particular From the German patent specification 875 389 is a ver for use as surgical suture material by drive to the production of threads and strings, extrusion of from animal tendons in usual special surgical sewing threads, strings for music-wise made homogeneous dispersions