CA1045548A

CA1045548A - Tissue absorbable polymer sponge

Info

Publication number: CA1045548A
Application number: CA219,627A
Authority: CA
Inventors: Donald J. Casey
Original assignee: American Cyanamid Co
Current assignee: Wyeth Holdings LLC
Priority date: 1974-03-25
Filing date: 1975-02-07
Publication date: 1979-01-02
Also published as: US3902497A; BR7531268A; JPS51116079A; IT1050278B; AR205109A1; FR2265412B1; FR2265412A1; AU7822275A; GB1490425A; DE2513159A1

Abstract

ABSTRACT OF THE INVENTION

A conformable tissue absorbable surgical sponge is formed by dissolving a tissue absorbable polymer is hexa-fluoroisopropyl alcohol or hexafluoroacetone sesquihydrate, filtering, freezing and subliming off the solvent to give a tissue conformable flexible sponge which rapidly absorbs blood and other body fluids. The sponge may be used to absorb blood or other liquids during a surgical procedure or may be used as a hemostat and allowed to remain in a closed wound with the polymer being absorbed by living tissue.

Description

25,013 ~o45s48 BACKGROUND OF ~HE I~ENTION
Surgical sponges find many uses in which an ab~
sorbent sponge is desirable to soak up blood, serum, or other body fluids, which sponges are removed and discarded. Cotton gauze sponges are used in many instances. When used inter-nally, there is a problem of part of the sponge coming off -and leaving threads or larger portions of the sponge in the wound. Concern over leaving a sponge in a patient complicates operating room practice and involves extremely rigorous count-ing procedures to insure that no sponge is accidentally left in a closed wound.
In many surgical procedures reguiring a hemostat to control bleeding sutures and tieoffs can be used. In some in-stances it is highly desirable that additional methods of controlling bleeding be made available. More or less success-ful efforts have been made to secure conformable hemostats which can be used to control bleeding and then left in the wound. The problem is well recognized and more acceptable - devices are in constant demand. ~
DESCRIP~ION 0~ TH~ PRIOR AR~ ~ -The use of polyglycolic acid is disclosed in a series of patents and applications to Schmitt, et al: -. .
U. S. Patent 3,297,033, Schmitt and Polistina, January 10, 1967, SURGICAL SUTURES, discloses polyhydroxy--acetic ester absorbable sutures. ~he material is also called polyglycolic acid, and is disclosed as permitting small quan- ~ -tities of comonomers to be present, such as dl-lactic acid, its optically active forms, homologs and analogs. A small - ~-quantity is recognized by the art as up to 15%, as shown by : , ~- 30 U. S. Patent 2,668,162, ~owe, ~ebruary 2, 1954, PREPARATION
0~ HIGH MO~ECU~AR WEIGH~ PO~YHYDROXY-ACETIC ES~ER. -~ ~

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25,013 55~8 U. S. Patent 3,463,158, Schmitt and Polistina, August 26, 1969, PO~YGLYCOLIC ACID PROS~HETIC DEVICES, dis-closes surgical uses of polyglycolic acid, and incorporates definitions of some terms.
U. S. Patent 3,620,218, Schmitt and Polistina, November 16, 1971, CY~INDRICAL PROS~HE~IC DEVICES OF PO~Y-G~YCOLIC ACID, lists many uses of polygl~colic acid.
U. S. Patent 3,736,646, Schmit-t and Epstein, June 5, 1973, METHOD OF A~rlACHING SURGICA~ NEEDLES TO MUL~IFILAMEN~ -PO~YGLYCO~IC ACID ABSORBABIE SUTURES, discloses surgical elements of a copolymer containing from 15 to 8~ mol percent glycolic acid and 85 to 15 mol percent lactic acid.
U. S. Patent 3,739,773, Schmitt and Polistina, June 19, 1973, PO~YG~YCOLI~ ~CID PROS~HEr~IC DEVIC~S, claims particularly bone pins, plates, nails and screws of polygly-colic acid.
U. S. Application Serial No. 365,656, Schmitt and Polistina, May 31, 1973, SURGICA~ DRESSI~GS 0~ ABSORBABLE
POLYMERS, discloses additional subject matter on surgical dressings of polyglycolic acid. ;-~
U. S. Patent 3,739,773, supra, lis-ts a number of U~ S. patents on methods for preparing polyglycolic acid and starting materials therefor.
In U. S. Ratent 3,620,218, supra, in Column 2 are Z5 listed a number of medical uses of polyglycolic acids, in~
cluding in Column 2; line 52, knit-ted or woven fibrillar products, including velours, and mentioning specifically in -line 53, burn dressings; line 57, felt or sponge for liver hemostasis; line 63, foam as absorbable prosthesis; and in -lines 74 and 75~ burn dressings (in combination with other polymeric films).
U. S. Patent 3,737,440, Schmitt and Bailey, June 5 . . . - -3L~45S48 1973, POLYGLYCOLIC ACID IN SOLUTIONS, discloses solutions of polyglycolic acid in hexafluoroisopropyl alcohol and hexa- ~`
fluoroacetone sesquihydrate, as well as wet and dry spinning of filaments and casting of films using t:hese solutions.
U.S Patent 3,783,093, Gallacher, January 1, 1974, FIBROUS POLYETHYLENE MATERIALS, discloses a fibrillated ma-terial, mentioning poly(glycolic acid) among others~ in which one resin is mixed and fibrillated with another, and one resin leached out to give the product, a web of oriented, intercon-nected directional fiber-like strands, membranes, ribbons, branched ribbons and fibrils. These can be used as bandages and for other medical purposes. Example 15 shows 25 parts of poly(glycolic acid) and 75 parts of poly (methyl methacrylate) leached with acetone.
US Patent 2,899,362, Sieger, Valentine, and Weiden-heimer, Augu~t 11, 1959, HEMOSTATIC SPONGES AND METHOD OF PRE-PARING SAME, discloses a whipped starch-gelatin mixture which is aerated and dried to form a sponge which may be used for hemostatic purposes.
US Patent 3,653,383, Wise, April 4, 1972, ALGIN
SPONGE AND PROCESS THEREFOR, discloses algin sponges made by freeze-drying aqueous alginate dispersions or gels which can be used for burn dressings, and other surgical purposes. The product after use is water-disintegrative.
Commercially, an oxidized regenerated cellulose is available, as a gelatin foam distributed in sheet form. Both oE these are absorbable in tissues. Under some conclitions, the gelatin foam causes bile cysts. It is desirably wetted with saline at the time of use.

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The use of gauzes, felts, and knitted fabr;cs as a wound dressing is quite conventional. The use of collagenous products as a sponge or pad has been disclosed. The requirements for surgical hemostats are varied and more satisfactory hemostats than presently available are constantly in demand.
The present invention provides a method of making a hemostat comprising dissolving a ~issue-absorbable polymer seLected from polyglycolic acid, poly~N-acetyl-D-glucosamine), and poly(4-methyl, 1,4-dioxane 2,5-dione) in hexafluoroisopropyl alcohol or hexafluoroacetone sesquihydrate, filtering to remove any insoluble contaminants, freezing the solution and subliming off the solvent, whereby an absorbable sponge fibrillar structure is formed ~ -from ribbons having a thickness within the range of from 1 to 5 microns which is essentially non-directional and is readily conformable to tissue surfaces.
The present invention also provides a hemostatic surgical sponge of a tissue absorbable polymer selected from polyglycolic acid, polyXN-acetyl-D-glucosamine), and poly(~-methyl,1,4-dioxana-2,5-dione) in the form of a fibrillar sheet having interconnected ribbons having a thickness within the range of from 1 to 5 microns oriented anisotropically having a network of connecting elements, and which is sufficiently flexible to be readily con-formable to a wound surface.
Such sponges may be used in procedures in which the foam sponge is to be left in the wound and absorbed by body tissues and also sees great acceptance in sponges which are used to absorb blooa, serum or other liquids with the sponge being Temoved and discarded. Because there is the ever present risk of part of the sponge falling off and being left in the wound or through inadvertence being closed in the wound, it is desirable that tissue absorbable sponges be used for general surgical use, wherever tissue may grow into the sponge.
A sponge should have high absorptive capacity, should absorb :;~ ,.' .'""~:, ~, ..

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fluids, particularly blood, rapidly, should be strong enough to be readily handled in surgical procedures, and conformable enough that it fits into whatever topography and space that is available, and be soft enough so that it does not injure sensitive tissues.
The absorbability of the present sponges by the body reduces the risks from the inadvertent enclosure of portions of a hemostatic sponge in living tissue--because such portions are absorbed and removed by the tissue itself.

- 4a -: -25,013 ~ S ~8 Although freeze drying is a well-known technique~
it i5 usually drying of water from frozen compositions in which water is to be removed by sublimation; and the product is usually rather brittle and friable so that it is not readily conformable, and is easily broken.
Here the solvent, which is removed by sublimation, is hexafluoroisopropyl alcohol or hexafluoroace-tone sesqui-hydrate or a mixture of the two. The residual foam is softer and more conformable than products usually secured ``
from aqueous systems. I-t is, of course, not possible to use an aqueous system with the tissue absorbable polymer of this invention. ~he polymers are not water soluble.
Because ~he solvent is volatile, and is sublimed to remove the major portion, and the resulting cake is dried to remove the small remaining portion, the absorbable sponge `
struc-ture is more readily freed from other components than in a leach technique using a mixture of polymers in which ;~
one polymer is leached ou-t, thus requiring elimination of not only the leached polymer, but also the leaching solvent.
Because the term "freeze-drying" sometimes implies an agueous system, the term "sublimation-drying" is used in many places herei~ to accen-tuate tha-t it is an organic sol- ~`
vent system which is being subllmed so tha-t it could be ;
called solven-t-sublimation for sponge manufacture. Products prepared in an aqueous system are generally friable. Using -hexafluoroisopropyl alcohol or hexafluoroacetone sesquihydrate as a solvent for polyglycolic acid, and other tissue absorbable compositions~ yields a product which is readily flexible and tissue conformable.
3 Because homopolymeric polyglycolic acid is currently being used in sutures, has met wi-th the approval of many government agencies in many countries, is commercially avail , .

~)455~3 able, and i5 familiar to chemists, the present invention is primarily described in detail in relation to homopolymeric polyglycolic acid.
Polyglycolic acid containing up to 15~ of other un- -its, such as lac-tic acid units, is considered within the term 'polyglycolic acid'l as used herein unless specified as homopolymeric. Other materials such as poly(N~acetyl-D--glucosamine) and polymers of 4-methyl,1,4-dioxane-2,5-dione may be used.
The present invention is particularly useful with tissue absorbable polymers which are insoluble in common organic solvents.
The foam should conform to the surface of the tissue.
Conformation comprises an assessment of the suppleness, re-siliency, and foam's ability to mimic the topography of the wound in such a fashion that there is a minimum gap between the tissue and the foam which minimizes air gaps and pools of liquid. If pools of liquid build up, whether of serum or blood, such pools may become sites for the growth of unde-sirable microorganisms, particularly for external dressings.
If the foam conforms adequately to the surface of the wound, the body's own defense mechanisms are effective up to the zone of contact with the foam, and bacterial contamination is minimized.
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DRAWINGS
FIGURE 1 shows a scanning electron microscope photo-micrograph at 50 diameters magnification of the surface of a frozen and dried sample produced in accordance with Example .
FIGURE 2 is a portion of the same structure at 300 diameters magnification.

25 ,013 ~. .
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~IGURE 3 is a photomicrograph similar to FIGURE 1 ::
at 50 diameters magnifieation of the reverse side of the same structure.
FIGURE 4 is the same surface as FIGURE 3, but a-t 5 300 diameters magnification.
FIGURE 5 is a razor cut cross section of the same sample as FIGURE 1 at 50 diameters magnification.
FIGURE 6 is the same razor cut cross section as FIGURE 5 at 300 diameters magnification. ;~
A scale on each photomicrograph shows relative sizes.
As exemplified by the drawing, the polyglycolic acid ,-~forms ribbons and shows a fibrillar structure with the ribbons, sheets and fibers intereonnected with many of -the ribbons having eonsiderable greater width than thickness. ~he thiek-ness in general is within the range of~from about 1 to 5mierons. The drled strueture is spongy in eharacter but re-silient so as to be conformable to a wound surfaee and is no-t friable and brittle as are most frozen-dried solids in whieh the solids are dried from an agueous system.
Example 1 Polygl~eolie Aeid in Hexafluoroisoprop~l Aleohol 10.3 Grams of low erystallinity homopolymerie poly-glyeolie aeid was dissolved in 150 milllliters of hexafluoro-isopropyl aleohol by stirring at 36 to 37C. until solution resulted ~about 3 hours). The resulting solution was freed from dust and inadvertent traee eontaminants by fil-tration through a sintered glass filter~ and transferred to a flat bottom dish. An additional 100 milliliters of hexafluoroiso-propyl aleohol was used to dilute the solution to about L~o eoneentration (wt./vol.). The dish was surrounded by a solid earbon dioxide-aeetone mixture until the solution was solidly frozen. The dish in its frozen eondition was plaeed in a resin kettle whieh was sealed and eonneeted to a h-Lgh ~ . .

25,013 ~ ~ 4 5 ~ ~ ~

vacuum system. Vacuum was maintained using a solid carbon dioxide acetone cooled trap to protect -the vacuum pump for 16 hours during which time the kettle was allowed to warm up with the hexafluoroisopropyl alcohol being maintained in its ;
solid state by evaporative cooling, and with no meltbacks.
After the thus formed foam had only a few percen-t residual hexafluoroisopropyl alcohol therein, the foam cake was re-moved, cut into 1/8 inch thick slices and further subjected to vacuum and heat at about 55C. until substantiall~ all of .,. , the hexafluoroisopropyl alcohol was removed.
m e solvent free foam was placed in strippable packages, sterilized with 12~o ethylene oxide in dichlorodi-fluoromethane and thus kept dry and sterile untll -time of use.
~ s a hemostatic sponge, the foam conEorms well to a wound and arrests the flow of blood immediately. ~he initial arresting of bleeding is largely mechanical. Blood then coagu- -lates in the sponge, which both arrests the further flow of blood, and tends to hold the sponge in position. The slices can be cut or broken into a size and shape adapted to cover a particular wound. ~he foam is usable in a wound whlch is to be closed, such as, for example, on the surface of the liver wi-th the foam being closed into -the abdominal cavity, or it may be used on the surface of the body as protection, and allowed to remain until the wound is healed. The foam may be used as an absorbent to absorb blood and other fluids at the site of a wound to dry the wound for subsequent suturing or closing as reguired by a particular surgical procedure.
In test animals on sacrifice, the foam is found to be essentially absorbed within 90 days.

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5~8 'Example 2 Polyglycollc Acid in Hexafluoroacetone Sesquihydrate 1.9 Grams of homopolymeric polyglycolic acid was dissolved in 45 ml. of hexafluoroacetone sesquihydrate by heating the mixture of 50C with stirrinq for three hours, yielding a solution having a concentration of approximately 4~2%(wt./vol.). The solution was filtered through a sintered glass filter and transferred to a flat dish and the clear ' amber solution was qet in a solid carbon dioxide-acetone mix-ture for about an hour until frozen completely solid.
The dish was then placed in a vacuum chamber and the hexafluoroacetone sesquihydrate was sublimed off at a reduced pressure of about 1 torr. A~ter about 24 hours, the spongelike foam obtained was removed, sliced into 1/8 inch thick slices, and again placed in a closed chamber evacuated '~
at 1 torr. with heating to about 80C for seyeral days. The product was then essentially free from solvent. The slices were sealed in strippable packages, sterilized with ethylene oxide and kept dry until time for use, using techniques rou-tinely employed for polyglycolic acid sutures.
The sponge was an effective absorbent for blood and served as an effeckive hemostat on wound surfaces.
In accordance with conventional usage in the poly-mer field, the polymers herein described are named from the monomer or monomers from which the polymers can be considered as formed. For instance, the key polymer, polyglycolic acid, is so~named whether made from glycolic acid or glycolide, ~ ' even though the units in the chain could properly be describ-ed as glyco1yl linkage~. Particularly, when considered with the prior art, and commercial usage in the field, such nomen-clature is regarded as historically the most signiEicant and the least ambiguous.
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Claims

The embodiments of the invention in which an exclusive pro-perty or privilege is claimed are defined as follows:

1. A method of making a hemostat comprising dis-solving a tissue-absorbable polymer selected from polygly--colic acid, poly(N-acetyl-D-glucosamine), and poly(4-methyl, 1,4-dioxane-2,5-dione) in hexafluoroisopropyl alcohol or hexafluoroacetone sesquihydrate, filtering to remove any in-soluble contaminants, freezing the solution and subliming off the solvent, whereby an absorbable sponge fibrillar struc-ture is formed from ribbons having a thickness within the range of from 1 to 5 microns which is essentially non-direc--tional and is readily conformable to tissue surfaces.

2. The method of Claim 1 in which the tissue ab-sorbable polymer comprises glycolic acid, having such a high glycolic acid content that it is insoluble in common organic solvents.

3. The method of Claim 2 in which the tissue ab-sorbable polymer is homopolymeric polyglycolic acid.

4. A hemostatic surgical sponge of a tissue ab-sorbable polymer selected from polyglycolic acid, poly(N--acetyl-D-glucosamine), and poly(4-methyl,1,4-dioxane-2,5--dione) in the form of a fibrillar sheet having interconnec-ted ribbons having a thickness within the range of from 1 to 5 microns oriented anisotropically having a network of con-necting elements, and which is sufficiently flexible to be readily conformable to a wound surface.

5. The sponge of Claim 4 in which the tissue ab-sorbable polymer comprises glycolic acid, having such a high glycolic acid content that it is insoluble in common organic solvent.

6. The sponge of Claim 4 in which the tissue ab-sorbable polymer is homopolymeric polyglycolic acid.