Note: Descriptions are shown in the official language in which they were submitted.
~ 5iS GBE-435
BACKGROUND OF THE INVENTION
Field of the Invention
This invention relates to a bone sealant, and more par-
ticularly, to an absorbable, semisolid composition for the con-
trol of osseous hemorrhage.
Descri~tion of Prior Art
Various substances and compositions have been employed
by members of the medical profession to control the bleeding
from cut bone surfaces. One class of materials used for the con-
trol of this type of hemorrhage is called bone wax. Bone waxesare used for the purpose of controlling hemorrhages from the cut
surfaces of bones, such as those of the skull, by forcibly smear-
ing the wax over the cut surface so that the material acts
mechanically to occlude and seal the open ends of the bleeding
osseous vessels and sinuses.
Bone waxes used in surgery today are generally prepared
from refined beeswax which has been admixed with other nonabsorb-
able and water insoluble hydrocarbons and vegetable oils. Cer-
tain disadvantages inhere in these bone wax compositions, as for
example, relatively poor adhesion properties, separation of wax
components and the hard, brittle state of the wax at room tem-
peratures requiring use at elevated temperatures.
U.S. Patent No. 3,395,217 discloses nonabsorbable bone
wax compositions comprised of low molecular weight ethylene co-
polymer waxes containing from about 15 to about 40 percent byweight of another unsaturated constituent and having molecular
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weights in the range of 1000 to 4000. These waxes have a semi-
solid consistency such that they can be kneaded between the
fingers when at room temperature and have the right amount of
tack and adhesion so that they can be easily manipulated in the
hands of the surgeon or applied by any suitable applicator such
as a gloved finger, spatula or appropriate disposable applicator.
Absorbable bone waxes have also been suggested. U.S.
Patent No. 2,772,999 describes a bone wax comprised of a water
soluble innocuous base and free acid cellulose glycolic acid
ether or free acid cellulose hydroxypropionic acid ether as a
hemostatic agent. The composition also preferably contains a
tackifier such as cellulose glycolic acid ether salt or cellulose
hydroxypropionic acid ether salt (preferably sodium salt) and
water as a plasticizer.
The Annals of Surgery 132, 1128 (1950) describes an ab-
sorbable hemostatic bone wax containing powdered oxidized cellu-
lose as the hemostatic agent in a base of polyethylene glycol.
The base is a mixture of high and low molecular weight poly-
ethylene glycols selected to provide the malleability and con-
sistency of material desired for this application.
The present invention provides a new absorbable bone
sealant which is a putty-like semisolid at room temperature.
The softness of the composition allows the material to be pack-
aged in a syringe, plastic or coated paper envelope, or aluminum
or glass tube from which it may be extruded or dispensed in de-
sired amounts during use. The sealant has sufficient tack so
that it adheres to bone surfaces, yet is easily manipulated in
the hands of the surgeon without crumbling or sticking to the
surgeon's gloves.
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Absorbable bone sealants of the present invention
comprise a mixture of from about 10 to 50 percent by weight
hemostatic powder in an absorbable, innocuous base containing
a small amount of a tackifying agent. The hemostat comprises
a mixture of fibrin and collagen powders, preferably in subs-
tantially equal proportions. The base is preferably a mixture
of water and poly-ol such as glycerol, and the tackifying
agent is preferably a polyglucoside such as dextran. The
sealant is formulated to the consistency of a semisolid which
is extrudable from a large orifice syringe. The composition is
packaged in a syringe, plastic envelope, or aluminium tube
and sterilized by radiation. During use, small amounts of
the sealant may be extruded from the package as required by the
surgeon. The composition is effective to control osseous
hemorrhage from cut bone and does not interfer with subsequent
healing and rejoining of bone parts.
The invention relates to an absorbable hemostatic
composition for use in the control of osseous hemorrhage
comprising from 10 to 50 percent by weight of a hemostatic
powder in a water-soluble, biocompatible base, said hemostatic
powder comprising a mixture of from about 40 to 95 percent by
weight fibrin powder and from about 5 to 60 percent by weight
collagen powder, the physical consistency of said hemostatic
composition being that of an extrudable semisolid.
The hemostatic compositions of the present invention
comprise a mixture of a hemostatic powder, an innocuous
absorbable base, and a tackifying agent, all formulated to
obtain a semisolid material which may be readily spread upon
the surface of cut bone in order to arrest the flow of blood.
Fibrin powder useful in the present invention may be
obtained from human or animal blood according to the method
disclosed in U.S. Patent No. 3,523,807.
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The fibrin powder is preferably reduced to a
particle size of 500 microns or smaller, and most preferably
to a size of about 200 microns. The fibrin powder thus
obtained comprises from about 10 to 50 percent by weight of
the total hemostatic composition.
Collagen powder, useful in the present invention, is
`a finely divided, fluffy material which may be prepared accord-
ing to the method disclosed in U.S. Patent No. 3,7421955. The
collagen powder is preferably reduced to a particle size of
2 mm or less, and most preferably to less than 1 mm.
The collagen powder and fibrin powder are mixed in
a ratio of 40-95 percent by weight fibrin, 5-60 percent by
weight collagen, in order to obtain a final product having the
desired characteristics of softness and malleability. In a
particularly preferred composition of this invention, subs-
tantially equal proportions of fibrin and collagen powders
are used with good results.
The base component of the hemostatic composition may
be an aqueous solution of a single substance or a mixture of
two or more water-soluble innocuous substances. Substances
suitable as bases include nonvolatile compatible poly-ol
compounds such as glycerol, propylene glycol, polymerized low
molecular weight aliphatic glycols such as polymerized ethylene
glycol and low molecular weight ethers or esters of polyglycols
such as the
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methyl, ethyl, or propyl ethers of polyethylene glycols and the
acetic or propionic esters of polyethylene or polypropylene
glycols. Glycerol and polyethylene glycols are the preferred
base materials, and polymerized ethylene glycols having a
molecular weight in the range of 200 to 4000 and a consistency
varying from a liquid of low viscosity to that of a waxy solid
may be found suitable. If desired, a polymerized ethylene glycol
having a molecular weight of 1000 to 4000 may be used in combina-
tion with a polymerized ethylene glycol having a molecular weight
of 200 to 600.
In addition to the hemostatic agent and innocuous base,
the bone wax composition also contains a tackifier such as a
polyglucoside, gelatin or collagen gels, polyvinyl pyrrolidone,
cellulose esters or other derivatives of cellulose such as oxi-
dized ceilulose, certain water soluble starches, or sugars. A
preferred polyglucoside is dextran while a preferred cellulose
derivative is cellulose glycolic acid ether salt or cellulose
hydroxypropionic acid ether salt, most preferably the sodium salt.
The powdered fibrin hemostatic material and tackifying
agent are thoroughly dispersed in the aqueous base to provide a
semisolid composition which is readily spreadable on the surface
of cut bone. The desired consistency of the composition is ob-
tained by proper selection of the base material and the amount of
water admixed therewith.
The following examples are provided to further illustrate
preferred embodiments of the present invention.
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~1~9S15 GBE-435
EXP~LE I
A hemostatic composition was prepared by thoroughly
dispersing the following materials in the indicated proportions:
Hemostatic Agent
Fibrin powder (200 microns~ - 17.5 g
Collagen powder (2 mm) - 17.5 g
Tackifying Agent
Dextran (MW 60,000-90,000) - 8.0 g
Base
Glycerol - 30.0 g
Water - 27.0 g
Total 100 g
The composition had a semisolid,putty-like,slightly
sticky consistency. When loaded in a 1 cc hypodermic syringe
with the needle removed, the mixture was readily extruded through
the 1.6 mm diameter-opening of the syringe to form a ribbon of
material ready for use.
EXA~LE II
An extruded ribbon, 10 mm in length by 1.6 mm in dia-
meter of the hemostatic composition of Example I was implanted
in the lumbar muscles of 12 CFY strain rats weighing 250-300 kg.
Two rats were sacrificed after 3, 7, 14, 28, 49, and 70 days,
and the implant sites examined to determine absorption rates and
tissue reaction to the bone sealant. The bone sealant was sub-
stantially completely absorbed by the 14th day with only few
remnan~s of collagen being detectable. No trace of the sealant
was found after 28 days. No abnor~al tissue reaction was ob-
served during the test.
1119515 G~E-435
EXAMPLE III
Fourteen white male CFY rats, weighing 200-250 g, were
anesthetized, and under surgically sterile conditions, the frontal
and parietal bones of the skull were exposed. Four holes were
made, one in each quadrant of the skull, using a 2 mm burr on
an electric drill. The parietal hole on one side was filled with
a complete plug of the bone sealan of Example I, and the pari-
etal hole on the other side plugged with a commercial bone wax
control. One frontal hole was treated by spreading a small
amount of the bone séalant of Example I on the cut surface, while
the other hole was similarly treated with the bone wax control.
After 14 days, 12 rats were sacrificed and the wounds
examined to determine the histological effects of the bone seal-
ant and bone wax. The remaining 2 rats were sacrificed and ex-
amined after 28 days. The following results were noted with nosignificant differences between the 14- and 28-day examination
periods.
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A. Bone Sealant of Example I
i. Plugged holes. Holes filled with tissue
and bony edges lined with a layer of
osteoblasts. There was considerable evi-
dence of new bone formation in the area.
ii. Smeared holes. Similar to plugged holes,
but connective tissue depressed below the
level of the skull surface.
B. Bone Wax Control
i. Plugged holes. ~oles remained filled with
a solid plug of wax which was easily re-
moved. Hole was thickly roofed by connec-
tive tissue with evidence of a much thinner
tissue floor. There was no indication of
any significant tissue activity in plug
area.
ii. Smeared holes. Generally filled with con-
nective tissue, but with fragments of wax
- visible in many cases.
The composition of Example I is a specific illustration
of a generally preferred hemostatic composition having the fol-
lowing range of formulation:
Fibrin powder - 15-25%
Collagen powder - 15-25%
Dextran - 5-10%
Glycerol - 20~40%
Water - 20-30%
The precise composition illustrated in Example I was
selected from the above general formulation to provide a desir-
able combination of properties, particularly consistency and
adhesion or tack. Optimum formulations may vary somewhat from
that given in Example I depending upon the particular properties
of the individual ingredients.
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The preceding Examples are given by way of illustration
and are not limiting of the invention. As will be apparent to
those skilled in the art from the foregoing description of the
invention, a variety of bone sealant compositions may be formu-
S lated in accordance with the present invention utilizing a hemo-
static agent which is a mixture of fibrin and collagen powders
in a water soluble, biocompatible base. All such compositions,
whether explicitly or implicitly disclosed, are accordingly en-
compassed by the present invention.
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