U.S. patent number 3,902,497 [Application Number 05/454,353] was granted by the patent office on 1975-09-02 for body absorbable sponge and method of making.
This patent grant is currently assigned to American Cyanamid Company. Invention is credited to Donald James Casey.
United States Patent |
3,902,497 |
Casey |
September 2, 1975 |
Body absorbable sponge and method of making
Abstract
A conformable tissue absorbable surgical sponge is formed by
dissolving a tissue absorbable polymer in hexafluoroisopropyl
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.
Inventors: |
Casey; Donald James
(Ridgefield, CT) |
Assignee: |
American Cyanamid Company
(Stamford, CT)
|
Family
ID: |
23804270 |
Appl.
No.: |
05/454,353 |
Filed: |
March 25, 1974 |
Current U.S.
Class: |
604/369; 521/87;
521/97; 521/88; 606/154 |
Current CPC
Class: |
A61L
15/64 (20130101); A61L 15/425 (20130101); A61L
2400/04 (20130101) |
Current International
Class: |
A61L
15/16 (20060101); A61L 15/42 (20060101); A61L
15/64 (20060101); A61F 013/00 () |
Field of
Search: |
;128/155-157,290,296,325,334,335.5 ;260/2.5E |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Trapp; Lawrence W.
Attorney, Agent or Firm: Walker; Samuel Branch
Claims
I claim:
1. A method of making a hemostat comprising dissolving a
tissue-absorbable polymer in hexafluoroisopropyl alcohol or
hexafluoroacetone sesquihydrate, filtering to remove any insoluble
contaminants, freezing the solution and subliming off the solvent,
whereby an absorbable sponge structure is formed, which is
essentially non-directional and is readily conformable to tissue
surfaces.
2. The method of claim 1 in which the tissue absorbable 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 absorbable polymer is
homopolymeric polyglycolic acid.
4. A hemostatic surgical sponge of a tissue absorbable polymer
comprising glycolic acid, having at least 85% of the monomer units
of glycolic acid, whereby it is insoluble in common organic
solvents, in the form of a sheet having interconnected ribbons and
ligaments of a single polymer which is essentially non-directional
having a network of connecting elements, and which is sufficiently
flexible to be readily conformable to a wound surface.
5. The sponge of claim 4 in which the tissue absorbable polymer is
homopolymeric polyglycolic acid.
6. A hemostatic surgical sponge of a tissue absorbable polymer in
the form of a sheet having interconnected ribbons and ligaments of
a single polymer which is essentially non-directional having a
network of connecting elements, and which is sufficiently flexible
to be readily conformable to a wound surface; made by the process
of dissolving a tissue-absorbable polymer in hexafluoroisopropyl
alcohol or hexafluoroacetone sesquihydrate, filtering to remove any
insoluble contaminants, freezing the solution and subliming off the
solvent, whereby an absorbable sponge structure is formed, which is
essentially non-directional and is readily conformable to tissue
surfaces.
Description
BACKGROUND OF THE INVENTION
Surgical sponges find many uses in which an absorbent 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 internally, 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
counting procedures to insure that no sponge is accidentally left
in a closed wound.
In many surgical procedures requiring a hemostat to control
bleeding, sutures and tieoffs can be used. In some instances it is
highly desirable that additional methods of controlling bleeding be
made available. More or less successful 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.
DESCRIPTION OF THE PRIOR ART
The use of polyglycolic acid is disclosed in a series of patents
and applications to Schmitt, et al:
U.S. Pat. No. 3,297,033, Schmitt and Polistina, Jan. 10, 1967,
SURGICAL SUTURES, discloses polyhydroxyacetic ester absorbable
sutures. The material is also called polyglycolic acid, and is
disclosed as permitting small quantities 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 U.S. Pat. No. 2,668,162, Lowe, Feb. 2, 1954,
PREPARATION OF HIGH MOLECULAR WEIGHT POLYHYDROXY-ACETIC ESTER.
U.S. Pat. No. 3,463,158, Schmitt and Polistina, Aug. 26, 1969,
POLYGLYCOLIC ACID PROSTHETIC DEVICES, discloses surgical uses of
polyglycolic acid, and incorporates definitions of some terms.
U.S. Pat. No. 3,620,218, Schmitt and Polistina, Nov. 16, 1971,
CYLINDRICAL PROSTHETIC DEVICES OF POLYGLYCOLIC ACID, lists many
uses of polyglycolic acid.
U.S. Pat. No. 3,736,646, Schmitt and Epstein, June 5, 1973, METHOD
OF ATTACHING SURGICAL NEEDLES TO MULTIFILAMENT POLYGLYCOLIC ACID
ABSORBABLE SUTURES, discloses surgical elements of a copolymer
containing from 15 to 85 mol percent glycolic acid and 85 to 15 mol
percent lactic acid.
U.S. Pat. No. 3,739,773, Schmitt and Polistina, June 19, 1973,
POLYGLYCOLIC ACID PROSTHETIC DEVICES, claims particularly bone
pins, plates, nails and screws of polyglycolic acid.
U.S. application Ser. No. 365,656, Schmitt and Polistina, May 31,
1973, SURGICAL DRESSINGS OF ABSORBABLE POLYMERS now U.S. Pat. No.
3,875,937, discloses additional subject matter on surgical
dressings of polyglycolic acid.
U.S. Pat. No. 3,739,773, supra, lists a number of U.S. patents on
methods for preparing polyglycolic acid and starting materials
therefor.
In U.S. Pat. No. 3,620,218, supra, in Column 2 are listed a number
of medical uses of polyglycolic acids, including in Column 2; line
52, knitted 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. Pat. No. 3,737,440, Schmitt and Bailey, June 5, 1973,
POLYGLYCOLIC ACID IN SOLUTIONS, discloses solutions of polyglycolic
acid in hexafluoroisopropyl alcohol and hexafluoroacetone
sesquihydrate, as well as wet and dry spinning of filaments and
casting of films using these solutions.
U.S. Pat. No. 3,783,093, Gallacher, Jan. 1, 1974, FIBROUS
POLYETHYLENE MATERIALS, discloses a fibrillated material,
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, interconnected 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.
U.S. Pat. No. 2,899,362, Sieger, Valentine, and Weidenheimer, Aug.
11, 1959, HEMOSTATIC SPONGES AND METHOD OF PREPARING SAME,
discloses a whipped starch-gelatin mixture which is aerated and
dried to form a sponge which may be used for hemostatic
purposes.
U.S. Pat. No. 3,653,383, Wise, Apr. 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 in
a gelatin foam distributed in sheet form. Both of these are
absorbable in tissues. Under some conditions, the gelatin foam
causes bile cysts. It is desirably wetted with saline at the time
of use.
The complete disclosures of the above patents and articles are
hereby herein incorporated by this reference thereto.
The use of gauzes, felts, and knitted fabrics as a wound dressing
is quite conventional. The use of collagenous products as a sponge
or pad has been diclosed. The requirements for surgical hemostats
are varied and more satisfactory hemostats than presently available
are constantly in demand.
SUMMARY OF THE INVENTION
It has now been found that a hemostat can be made by dissolving a
tissue absorbable polymer in the very powerful solvents
hexafluoroisopropyl alcohol or hexafluoroacetone sesquihydrate,
preferably filtering the solution, freezing, and subliming off the
solvent, yielding a sponge which is readily conformable to wound
topography, highly absorbent and versatile. It 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 blood, serum or other liquids with the
sponge being removed 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
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.
Although freeze drying is a well-known technique, it is 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 hexafluoroacetone sesquihydrate or a
mixture of the two. The residual foam is softer and more
conformable than products usually secured from aqueous systems. It
is, of course, not possible to use an aqueous system with the
tissue absorbable polymer of this invention. The polymers are not
water soluble.
Because the 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 structure is more readily
freed from other components than in a leach technique using a
mixture of polymers in which one polymer is leached out, thus
requiring elimination of not only the leached polymer, but also the
leaching solvent.
Because the term "freeze-drying" sometimes implies an aqueous
system, the term "sublimation-drying" is used in many places herein
to accentuate that it is an organic solvent system which is being
sublimed so that it could be called solvent-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.
Because homopolymeric polyglycolic acid is currently being used in
sutures, has met with the approval of many government agencies in
many countries, is commercially available, and is 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 units, such as
lactic acid units, is considered within the term polyglycolic acid
as used hereien unless specified as homopolymeric. Other materials
such as poly(N-acetyl-D-glucosamine) and polymers of
3-methyl-1,4-dioxane-2,5-dione may be used.
Poly(N-acetyl-D-glycosamine) is described in U.S. Ser. No. 441,717,
filed on or about Feb. 11, 1974, Richard Carl Capozza,
POLY(N-ACETYL-D-GLUCOSAMINE) PRODUCTS.
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, resiliency, 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 undesirable 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.
DRAWINGS
FIG. 1 shows a scanning electron microscope photomicrograph at 50
diameters magnification of the surface of a frozen and dried sample
produced in accordance with Example 1.
FIG. 2 is a portion of the same structure at 300 diameters
magnification.
FIG. 3 is a photomicrograph similar to FIG. 1 at 50 diameters
magnification of the reverse side of the same structure.
FIG. 4 is the same surface as FIG. 3, but at 300 diameters
magnification.
FIG. 5 is a razor cut cross section of the same sample as FIG. 1 at
50 diameters magnification.
FIG. 6 is the same razor cut cross section as FIG. 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
interconnected with many of the ribbons having considerable greater
width than thickness. The thickness in general is within the range
of from about 1 to 5 microns. The dried structure is spongy in
character but resilient so as to be conformable to a wound surface
and is not friable and brittle as are most frozen-dried solids in
which the solids are dried from an aqueous system.
EXAMPLE 1
Polyglycolic Acid in Hexafluoroisopropyl Alcohol
10.3 Grams of low crystallinity homopolymeric polyglycolic acid was
dissolved in 150 milliliters of hexafluoroisopropyl alcohol by
stirring at 36.degree. to 37.degree.C. until solution resulted
(about 3 hours). The resulting solution was freed from dust and
inadvertent trace contaminants by filtration through a sintered
glass filter, and transferred to a flat bottom dish. An additional
100 milliliters of hexafluoroisopropyl alcohol was used to dilute
the solution to about 4% concentration (wt./vol.). The dish was
surrounded by a solid carbon dioxide-acetone mixture until the
solution was solidly frozen. The dish in its frozen condition was
placed in a resin kettle which was sealed and connected to a high
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 percent residual hexafluoroisopropyl alcohol
therein, the foam cake was removed, cut into 1/8 inch thick slices
and further subjected to vacuum and heat at about 55.degree.C.
until substantially all of the hexafluoroisopropyl alcohol was
removed.
The solvent free foam was placed in strippable packages, sterilized
with 12% ethylene oxide in dichlorodifluoromethane and thus kept
dry and sterile until time of use.
As a hemostatic sponge, the foam conforms well to a wound and
arrests the flow of blood immediately. The initial arresting of
bleeding is largely mechanical. Blood then coagulates 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. The foam is
usable in a wound which is to be closed, such as, for example, on
the surface of the liver with 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 required by a particular surgical procedure.
In test animals on sacrifice, the foam is found to be essentially
absorbed within 90 days.
EXAMPLE 2
Polyglycolic Acid in Hexafluoroacetone Sesquihydrate
1.9 Grams of homopolymeric polyglycolic acid was dissolved in 45
ml. of hexafluoroacetone sesquihydrate by heating the mixture of
50.degree.C. with stirring 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 set in
a solid carbon dioxide-acetone mixture 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. After 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 80.degree.C. for several 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 routinely employed for polyglycolic acid
sutures.
The sponge was an effective absorbent for blood and served as an
effective hemostat on wound surfaces.
In accordance with conventional usage in the polymer 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 described as glycolyl linkages. Particularly,
when considered with the incorporated cited prior art, and
commercial usage in the field, such nomenclature is regarded as
historically the most significant and the least ambiguous.
* * * * *