Note: Descriptions are shown in the official language in which they were submitted.
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It has been known that some sclero proteins
as, for example, collagen, keratin, and elas~in
can be transplanted homologously as well as hetero-
logously in humans and in animals, in order to allevi-
ate an existing deficiency of natural body tissues.
The receiving organism is able to recognize, more
or less well depending on the type of implant, that
a foreign protein is present. As a rule, decompo-
sition of the implanted substance takes place.
In a few cases, decomposition of the implant is
so slow that the body simultaneously is able to
produce new binding tissue. At this point we refer
to the "guide track principle" as it has been described,
for example, in German Patent No. 20 04 553.8-09.
It is understandable that the "guide track
principle" must fail when tissue production is slower
than tissue decomposition. Therefore, as a rule,
an increased resistance against tissue decomposition
activity induced by the body is desirable. Thus,
use of the lyophilized hard cerebral meninges of
the human as a transplant is almost essential in
neurosurgery. However, other collagens, which are
obtained from animals, play a useful role.
The brochure published by B. Braun Melsungen
AG: "LyoduraR for the Homoi Plastic Replacement
of Body Structures" in 1978, and the numerous litera-
ture references mentioned therein, establish the
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importance and usefulness placed on implantable
sclero proteins in the medical field.
Presently, freeze-drying and acetone drying
are the principal methods used in preparing trans-
plants from sclero proteins. However, the biological
stability of the products thereby obtained is often
unsatisfactory, especially when used in replacing
the mechanically stressed organs as, for example,
fasciae, bands, and tendons. If the stability of
the implant decreases faster in the body than the
new structure which is produced by the body in healing
the wound, a successful operation is not achieved
and the patient suffers corresponding harm.
An object of the invention is to provide
a process by which the biological stability of the
sclero protein transplants is improved.
By experimental tests, we found, surprising-
ly, that the resistance of sclero proteins to biologi-
cal decomposition can be substantially improved
by a modified drying process.
The attached drawing constitutes a graph
which shows, for example, the advantage obtained
by using the prGcess of the invention. The drawing
illustrates the change in the tensile strength of
10 mm wide strips of hard cerebral meninges of the
human after implantation beneath the skin on the
back of rabbits. 210 of those strips were implanted
and taken out at various times after the operation
to measure the tensile strength of the strips.
The curve A was derived from tests with acetone
dried cerebral meninges, curve B with freeze-dried
cerebral meninges and curve C with cerebral meninges
which had been manufactured according to the process
of the invention.
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While the curves in the drawing show there
was no significant difference in the tensile strength
between the products produced by acetone drying
and freeze drying during the thirty-one day observa-
tion period, the material manufactured according
to the invention showed an increase in tensile strength
by a factor of 1.7 to 7Ø
The desired characteristics can be achieved
by introducing the sclero protein material into
a glycerin solution, after prior conventional proce-
dural steps of purifying and antigen separation.
Water is removed from the material in the glycerin.
Simultaneouslyl glycerin impregnates the transplant
by a diffusion process. During the subsequent drying
process the percentage content of glycerin increases
substantially. Similar results can be obtained
with polyethylene glycol having a molecular weight
of about 400 to 20~0.
Glycerin or polyethylene glycol which
has diffused into the sclero protein material acts
as a protective factor during freezing. However,
this fact, which has been known as such, is not
responsible for the increased biological stability
after it is used as an implantation, for it became
evident that the freeze drying can be substituted
by air drying at room temperature without adversely
affecting the resistance which the sclero protein
has against decomposition in a living organism.
The process is carried out in that one
first wets the sclero proteins as, for example,
collagen, keratin, elastin from humans or animals
and, in particular, raw dura matter from humans,
with water in the usual way. Then one treats it
with H2O2, thereafter one degreases it, rinses it
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with water, dries and sterilizes it, but wherein,
according to the invention, the glycerin or polyethylene
glycol treatment step is inserted between the rinsing
and drying steps.
The glycerin can be used in a 5% to 50%
by weight, preferably in a 20~ to 40% solution,
in water. A 30% glycerin solution in water is par-
ticularly useful.
Polyethylene glycol useful in the process
has a molecular weight of about 400 to 2000 and
it is usually used in a 5% to 50% by weight polyethylene
glycol, in particular in a 20% to 40~ solution,
in water.
The following advantages over the prior
art are achieved by the process according to the
invention:
The product is soft and no rehydration
is necessary prior to its use.
The product is transparent; for example,
during brain operations one can see
the fluid and the brain surface through
the transplant.
The product has increased biological
stability.
The process according to the invention
is explained in detail by means of the following
example describing the manufacture of soft dry dura.
Example
Raw dura matter which was supplied in
concentrated NaCl was watered for 24 hours. Thereupon
it was put into 2% to 20%, preferably 5%, H2O2 for
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48 hours. Then the dura matter was degreased in
a Soxhlet apparatus in acetone-diethylether 1 : 1
for 4 hours. The degreased dura matter was rinsed
for 12 to 24 hours with water.
The dura matter treated in this way was
stirred for 4 hours in a 30~ glycerin solution in
water. The moist dura matter which was obtained
was freeze dried in a lyophilizer. As an alternative,
the moist dura matter was dried at room temperature
in the open air.
After drying for 12 hours, the soft dry
dura matter was taken out and sterilized with 2.5
Mrad. The dura matter was soft, transparent and
had increased biological stability. The dura matter
obtained according to the processes known up to
now was substantially harder, not transparent and
had a lower biological stability.
The following data in connection with
the attached drawing show the surprising resul~s
of the comparative tests.
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Tabular Chart of the Tensile Strength of the Dura
Strips (Width 10 mm) after Implantation.
Data in Kp, (n = 10 per group, each point of the
curve in the drawing is based on 10 individual measure-
ments).
Implantation Time Lyodura Tutoplast Soft Dura
(days) Obtained by Obtained by According to
Freeze Drying Acetone Drying the Invention
0 1.9 + 0.9 2.0 + 0.5 3.2 + 1.3
100% + 47 105% + 26 168% + 68
1 1.9 + 1.7 1.7 + 0.3 3.5 + 0.9
100% + 37 89% + 16 184% + 47
4 1.4 + 0.6 1.2 + 0.4 3.9 + 0.7
74% + 32 63% + 21 205% + 37
7 1.4 + 0.6 0.7 + 0.3 4.4 + 1.6
74% + 32 37% + 16 232% + 84
14 1.3 + 0.6 0.7 + 0.4 3.8 + 1.7
68~ + 32 37% + 21 200% + 90
21 1.0 + 0.5 0.7 + 0.3 2.6 + 1.0
53% + 26 37~ + 16 137% + 53
31 0.9 + 0.8 0.4 + 0.6 2.8 - 1.7
47% + 42 21% + 32 147% + 90
Second line = data in %
O-value Lyodura ~ 100~
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The soft dura matter obtained according
to the invention can be used as transplants in various
areas of medical use which are well known to those
skilled in the art. A great number of those areas
of use are mentioned on page 2 in the above-named
brochure of the firm B. Braun Melsungen.
