DE2513159A1 - HEMISTIC SPOOLS AND METHOD FOR PRODUCING THEM - Google Patents

Description

MAAS - SE ¹ LSR

ϊ £ ί .. '. Ι .... νϊτϊ. -99

Case 25 013

American Cyanamid Company, Wayne, Mew Jersey / USA

Hemostatic sponges and processes for their manufacture

The invention relates to a method for producing surgical Sponges made from synthetic polymers that can be absorbed by the tissue, as well as the sponges formed in the process.

Surgical sponges are widely used for soaking up blood, serum, and other body fluids, and then removed and discarded. Cotton gauze sponges are used in many cases. When the sponges are used inside the body there is a risk that part of the sponge will peel off and that threads or larger pieces of the sponge will get into the wound lag behind. The hatreds used to prevent a sponge from being left in a patient's closed wound, complicate operations in the operating room and require extremely strict counting measures to ensure that not accidentally leaving a sponge in a closed wound. · ■ _; .

50984 1/0686

In many surgical methods, the blood vessels can be sutured or tied to stop the blood. In certain In some cases it is highly desirable to have additional bleeding control methods available. There are more or less successful attempts have been made to create hemostatics that adapt to the wound and are used for treatment the bleeding and then left in the wound. The problem is well known and persistent Need for more satisfying products of this kind.

Hemostatic sponges and tissue absorbable materials j synthetic polymers are well known. For example, US Pat. No. 3,297,033 describes the use of polyglycolic acid described. The patent specifically describes absorbable sutures, sponges, prosthetic devices and the like from polyhydroxyacetic acid esters. The material is also referred to as polyglycolic acid and it is stated that small amounts of comonomers may be present, such as dl-lactic acid, the optically active forms of this compound as well as homologous and analogous substances. As small amounts are dated Prior art up to 15% understood what from U.S. Patent 2,668,162 to Lowe (February 2, 1954) "Preparation of High Molecular Weight Polyhydroxy-Acetic Ester ".

U.S. Patent 3,463,158 to Schmitt and Polistina (Aug. 26, 1969), "Polyglycolic Acid Prosthetic Devices" discloses the surgical technique Use of Polyglycolsäux-e and contains the definition some technical terms.

U.S. Patent 3,620,218 to Schmitt and Polistina (Nov. 1971), "Cylindrical Prosthetic Devices of Polyglycolic Acid", counts a number of uses for polyglycolic acid on.

U.S. Patent No. 3,736,646 to Schmitt and Epstein (June 5, 1973), "Method of Attaching Surgical Needles to Multifilament Poly-

5098 41/0686

Glycolic Acid Absorbable Sutures, "deals with surgical Elements made of a copolymer containing 15 to 85 mol% Contains glycolic acid and 85-15 mol% lactic acid.

In U.S. Patent No. 3,739,773 to Schmitt and Polistina (June 19, 1973), "Polyglycolic Acid Prosthetic Devices" are pins, plates, nails and screws especially intended for bone treatment from polyglycolic acid claimed.

In the above-mentioned US Pat. No. 3,739,773 there are a number of US patents indicated, which deals with processes for the preparation of polyglycolic acid and the starting materials suitable therefor deal.

Column 2 of the aforementioned US Pat. No. 3,620,218 shows a number of medical uses for polyglycolic acid listed, namely at line 52 knitted or woven fiber products, including velor, and processes, at line 53 Bandages for burn wounds, in line 57 felts or sponges for hemostasis in the liver, in line 63 absorbable foams prosthetic materials, and at lines 74 and 75, bandages for burn wounds (in combination with others Polymer films).

In U.S. Patent 3,737,440 to Schmitt and Bailey (June 5, 1973), "Polyglycolic Acid in Solutions," are solutions of polyglycolic acid in hexafluoroisopropyl alcohol and hexafluoroacetone sesquihydrate, the manufacture of threads by wet and dry spinning these solutions and the production of foils and films by casting these solutions.

U.S. Patent No. 3,783,093 to Gallacher (Jan. 1, 1974) "Fibrous Polyethylene Materials" discloses a fibrous material to which Manufacture of a resin called polyglycolic acid, mixed with another resin and made into fibers, after which a resin is dissolved out, so that one is a product

5 0 9 8-1 / 0686

Woven fabric made of oriented, interconnected, directed, fiber-like strands, membranes, ribbons, branched ribbons and fibrils. These products can be used as bandages and for other medical purposes. In example 15 a material is leached with acetone, which consists of 25 parts of polyglycolic acid and 75 parts of polymethyl methacrylate.

Hemostatic sponges made from natural polymers are also known. For example, US Pat 2,899,362 to Sieger, Valentine, and Weidenheimer (Aug. 11, 1959), "Hemostatic Sponges and Method of Preparing Same", one Whipped starch-gelatin mixture described, which is aerated and dried to form a sponge, which is used for Hemostasis can be used.

In U.S. Patent 3,653,383 to Wise (April 4, 1972), "Algin Sponge and Process Therefor", algin sponges are identified as being Dressing materials can be used for burns or for other surgical purposes and are obtained thereby, that aqueous alginate dispersions or gels are freeze-dried. After use, the product can be decomposed in water.

The use of gauze, felt and knitted fabrics as Wound dressing materials are common. Also the use of collagen products as sponges or pillows or tampons is has been described. The requirements for surgical hemostatic materials vary and there is an ongoing one Need for more satisfactory hemostatic materials.

It has now been found that a hemostatic sponge can be made by using a synthetic one Polymer that can be absorbed by the tissue in the very strong solvents hexafluoroisopropyl alcohol or Hexafluoroacetone sesquihydrate dissolves - the solution is preferably filtered, if insoluble materials are present, the solution

509841/0686

freezes and sublimates the solvent, leaving a sponge that adapts easily to the wound, has a strong absorbent effect and can be used in a variety of ways. It can be used where the Foam sponge remains in the wound and is absorbed by the body tissue and can also be used there with advantage, where the sponges are used to absorb blood, serum and other fluids and then removed and discarded will. Since there is always the risk that part of the sponge falls off and remains in the wound or inadvertently in When the wound is enclosed, it is desirable that tissue-absorbable sponges always be used for general surgical purposes Purposes are used when the tissue can grow into the sponge.

A sponge should have a high absorbency if it should absorb liquids, especially blood, quickly be stable enough to be easily handled during surgical operations, should be sufficiently malleable to adapt to the existing surface structure and space and should ultimately be so soft that that no damage is caused to sensitive tissues.

The fact that the sponges according to the invention can be absorbed by the body reduces the risks which consist in parts of a hemostatic sponge being enclosed in living tissue as these parts absorbed by the tissue and thus removed.

Although freeze drying is a well known technique, it usually involves the dehydrating drying of frozen compositions, from which the water is to be removed by sublimation. This usually gives a fragile one and fragile product that cannot be easily deformed and easily breaks apart.

509841/0686

In the present case, the solvent that is removed by sublimation is hexafluoroisopropyl alcohol or hexafluoroacetone sesguihydrate or a mixture of these two solvents. The resulting foam is softer and more deformable than products that are usually obtained from aqueous systems. It is of course not possible to use an aqueous one To use the system for the absorbable polymer used according to the invention, since the polymers are not water-soluble are.

Because the solvent is volatile and the majority of the solvent is removed by sublimation, wherein the cake formed is preferably dried to the remainder Eliminating some of the solvent makes the absorbable sponge structure easier than in the case of the leach technique the polymer is leached out of a polymer mixture, freed from other constituents, so that according to the invention not only the leached polymer, but also the leaching one Solvents are not necessary.

Since the term "freeze-drying" is in certain cases an aqueous System is based, the term "sublimation drying" is used in many places in the following to emphasize that the sublimed system is an organic solvent system acts, so that the invention could also be referred to as solvent sublimation for sponge manufacture. The products prepared from aqueous systems are generally brittle. By using hexafluoroisopropyl alcohol or hexafluoroacetone sesquihydrate as a solvent for polyglycolic acid and other tissue absorbable compositions a product is obtained which is easily deformable and adapts to the fabric.

By the freeze-drying or used according to the invention Sublimation drying process results in a hemostatic

509841/0686

~ π -

the surgical sponge made of a synthetic tissue absorbable Polymer in the form of a sheet, which comprises anisotropically arranged ribbons and threads, which form a network have connecting elements. The sponge is essentially non-directional and sufficiently flexible to move without further adapt to the surface of a wound.

Since the homopolymeric polyglycolic acid is currently used for sutures, it is recognized by the authorities in many countries, commercially available and familiar to the chemist, the invention will be described in more detail below with reference to the homopolymeric polyglycolic acid described.

Polyglycolic acid, which contains up to 15% other units, such as lactic acid units, is also encompassed by the term "polyglycolic acid" as used herein, when not as is called homopolymer. Other materials can also be used as synthetic polymers to be absorbed by the tissue such as poly (N-acetyl-D-glucosamine) and polymers of 4-methyl-1,4-dioxane-2,5-dione.

The teaching according to the invention is particularly suitable for tissue-absorbable Polymers which are insoluble in common organic solvents.

The foam should adapt to the surface of the fabric. The adaptability depends on the softness, the elasticity and the ability of the foam to conform to the surface shape of the wound so that there is minimal clearance is present between the fabric and the foam, eliminating the presence of air bubbles and fluid build-up is kept to a minimum. If fluid builds up, it can, whether it is serum or blood acts, which form places for the growth of undesirable microorganisms, which is particularly the case with external associations of the

.5 09841/0688

Case is. If the foam adheres adequately to the If the surface of the wound adapts, the body's own defense mechanism remains effective up to the area of contact with the foam so that bacterial contamination is kept to a minimum will.

Further embodiments / advantages and objects of the invention result from the following description, the examples and the drawings.

Fig. 1 is one with a scanning electron microscope photomicrograph obtained at a magnification of 50 times (Diameter) of the surface of a sample frozen and dried according to Example 1.

Fig. 2 shows part of the same structure at 300 times magnification (diameter).

FIG. 3, similar to FIG. 1, shows a photomicrograph with 50-fold magnification (diameter) of the rear side of the same structure.

FIG. 4 shows the same surface as FIG. 3, but with a 300-fold magnification (diameter).

FIG. 5 shows a razor blade section through the sample shown in FIG. 1 with a 50-fold magnification (diameter) shown.

FIG. 6 shows the same razor blade cut as the figure, but with a 300-fold magnification (diameter).

A scale is indicated on each photomicrograph that shows the relative proportions.

50 9 84 1/0686

As can be seen from the drawings, it forms polyglycolic acid Ribbons or threads and shows a fiber structure in which the ribbons, sheets and fibers are connected to one another, with a plurality of the ribbons being of a substantially greater width than Own thickness. The thickness is generally in a range from about 1 to 5 µm. The dried structure has a Sponge character, but is elastic so that it can adapt to the surface of the wound and is not brittle or fragile brittle like most freeze-dried solids formed by drying from aqueous systems.

In accordance with customary practice in polymer chemistry, the polymers described herein are prepared using the or denotes the monomers from which the polymers are formed. E.g. the key polymer, polyglycolic acid, referred to in this way, regardless of whether it was formed from glycolic acid or glycolide, although the units of Chain can be referred to as glycolyl bridges.

The following examples serve to further illustrate the invention .

example 1

Polyglycolic acid in hexafluoroisopropyl alcohol

10.3 g of homopolymeric polyglycolic acid with low crystallinity are dissolved in 150 ml of hexafluoroisopropyl alcohol by stirring at 36 to 37 ° C until a solution is obtained (which takes about 3 hours requires). The resulting solution is filtered through a sintered glass filter from dust and other trace contaminants freed and poured into a flat-bottomed bowl. Another 100 ml of hexafluoroisopropyl alcohol is used to dilute the solution to a concentration

509841/0686

of about 4% (weight / volume). The peel is made with a mixture of solid carbon dioxide and acetone surrounded until the solution is frozen solid. Then the shell with the frozen Material is placed in a resin flask which is sealed and connected to a high vacuum system. The vacuum will using a cold trap that protects the vacuum pump and is charged with solid carbon dioxide and acetone while Maintain 16 hours, allowing the flask to warm and the hexafluoroisopropyl alcohol through the evaporator Maintains cooling in a solid state, causing melting to occur. After the foam formed in this way only still contains a few percent remaining hexafluoroisopropyl alcohol, the foam cake is removed, cut into 3.17 mm (1/8 inch) thick slices and treated in the Vacuum at about 55 ° C until essentially all of the hexafluoroisopropyl alcohol is removed.

The solvent-free foam is placed in tear-open packs, Sterilized with 12% ethylene oxide in dichlorofluoromethari and so kept dry and sterile until use.

As a hemostatic sponge, the material adapts well to the wound and stops the flow of blood instantly. The initial one Most of the bleeding is stopped mechanically. Then the blood coagulates in the sponge, which at the same time the further Shuts off blood supply and locks the sponge in place. The slices can be cut or broken in the size and shape necessary for the wound in question. The foam is also used for closing wounds suitable, for example on the surface of the liver, wherein the foam is enclosed in the abdominal opening, or the Foam can be applied to the surface of the body and left there until the wound has healed. Of the Foam can also be used as an absorbent to absorb blood and other fluids at the wound site, around the wound

509841/0686

Dry the wound for subsequent suturing or closing, as required for certain surgical procedures is.

By killing the test animals, the foam was found to be substantially absorbed within 90 days.

Example 2

Polyglycolic acid in hexafluoroacetone sesguihydrate

Dissolve 1.9 g of homopolymeric polyglycolic acid in 45 ml of hexafluoroacetone sesquihydrate by heating for 3 hours the mixture with stirring at 50 ⁰ C. A solution was obtained with a concentration of about 4.2% (weight / volume). The solution is filtered through a sintered glass filter and transferred to a shallow dish, after which the clear, amber-colored solution is placed in a mixture of solid carbon dioxide and acetone for about an hour until it is completely frozen solid.

The shell is then placed in a vacuum chamber and the hexafluoroacetone sesguihydrate is removed under reduced pressure from about 1 Torr sublimed. After about 24 hours, the resulting sponge-like foam is removed, in 0.32 cm (1/8 inch) thick slices cut up and placed again for several days in a chamber evacuated to 1 torr and reduced to about 80 ° C heated. The product is then essentially free of solvent. The slices are placed in tear-open packs, sterilized with ethylene oxide and kept dry until use, which is what is customary for polyglycolic acid sutures applied techniques.

The sponge is an effective absorbent for blood and acts as an effective hemostatic material on the surface of wounds.

509 8A 1/0686

Claims (5)

PATENT CLAIMS j; If process for the manufacture of hemostatic sponges, characterized in that one is a synthetic polymer which is absorbed by the tissue can, in hexafluoroisopropyl alcohol or hexafluoroacetone sesguihydrate dissolves, the resulting solution freezes and the solvent to form an absorbable, essentially The non-directional sponge structure that adapts easily to the tissue surface is sublimated. 2. The method according to claim 1, characterized in that that the polymer that can be absorbed by the tissue is polyglycolic acid, poly (N-acetyl-D-glucosamine) and / or polymers of 3-methyl-1,4-dioxane-2,5-dione are used. 3. The method according to claim 2, characterized in that the polymer is a homopolymer used by glycolic acid. 4. Hemostatic surgical sponge made of a synthetic polymer in the form of a sheet that can be absorbed by the tissue made of interconnected, anisotropically arranged threads and ribbons that form a network of connecting elements on iron, and which is essentially non-directional and so flexible that it easily attaches to the surface of the Adapts wound, obtainable by the method of claim 1. 5. Sponge according to claim 4, characterized in that it is polyglycolic acid as the polymer contains. 509841/0686 Sponge according to claim 5, characterized in that that it is homopolymeric polyglycic acid as a polymer contains. 50984 1/0686 Blank page