U.S. patent application number 17/504405 was filed with the patent office on 2022-09-08 for collagen powder.
This patent application is currently assigned to INNOCOLL PHARMACEUTICALS LIMITED. The applicant listed for this patent is INNOCOLL PHARMACEUTICALS LIMITED. Invention is credited to Alexandra DIETRICH, Michael Myers, Stefan Schneid.
Application Number | 20220281953 17/504405 |
Document ID | / |
Family ID | 1000006351565 |
Filed Date | 2022-09-08 |
United States Patent
Application |
20220281953 |
Kind Code |
A1 |
DIETRICH; Alexandra ; et
al. |
September 8, 2022 |
COLLAGEN POWDER
Abstract
There is a need to provide a collagen powder having desirable
product characteristics, such as high fluid absorption capacity,
while also having processing characteristics that allow commercial
manufacturing and handling of the collagen powder. The present
invention relates to a collagen powder, a method of manufacture
thereof, and uses thereof. In particular, the present invention
relates to a process for preparing a collagen powder, the process
comprising the steps of providing a collagen source; adjusting the
concentration of the collagen source; adjusting the pH of the
collagen source; freezing the collagen source; dehydrating the
frozen collagen; and degrading the dehydrated collagen to a
powder.
Inventors: |
DIETRICH; Alexandra; (Saal,
DE) ; Myers; Michael; (Ashburn, VA) ; Schneid;
Stefan; (Saal, DE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
INNOCOLL PHARMACEUTICALS LIMITED |
ATHLONE |
|
IE |
|
|
Assignee: |
INNOCOLL PHARMACEUTICALS
LIMITED
ATHLONE
IE
|
Family ID: |
1000006351565 |
Appl. No.: |
17/504405 |
Filed: |
October 18, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
13858382 |
Apr 8, 2013 |
|
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17504405 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
C07K 14/78 20130101 |
International
Class: |
C07K 14/78 20060101
C07K014/78 |
Claims
1-20. (canceled)
21. A collagen powder prepared by a method comprising the steps of:
(a) obtaining collagen from a collagen source; (b) adjusting a
concentration of the collagen to be in a range from 1.5% to 5.0%
and a pH of less than 4.5 to obtain adjusted collagen; (c) freeze
drying the adjusted collagen to obtain dried collagen; and (d)
mechanically processing the dried collagen to obtain the collagen
powder, wherein the collagen powder has a bulk density in a range
from 25 mg/cm.sup.3 to 35 mg/cm.sup.3 and a water uptake capacity
of absorbing at least 20 times more water in weight than a weight
of the collagen powder.
22. The collagen powder of claim 21, wherein in step (b), the
concentration of collagen is adjusted prior to adjusting the pH of
collagen.
23. The collagen powder of claim 21, wherein in step (b), the pH of
collagen is adjusted prior to adjusting the concentration of
collagen.
24. The collagen powder of claim 21, wherein in step (b), the
concentration of collagen and pH of collagen are adjusted
simultaneously.
25. The collagen powder of claim 21, wherein in step (b), adjusting
the pH comprises introducing acetic acid.
26. The collagen powder of claim 21, wherein step (c) comprises
freezing to a temperature of about -33.degree. C. to about
-42.degree. C.
27. The collagen powder of claim 21, wherein step (c) comprises
removing water substance from the adjusted collagen by reducing
pressure to be in a range from 0.05 mbar to 1 mbar.
28. The collagen powder of claim 21, wherein step (c) comprises
increasing the temperature to about +30.degree. C. at a rate of
about 0.3.degree. C. to about 1.5.degree. C. per minute.
29. The collagen powder of claim 21, wherein step (c) comprises
increasing the temperature to about +40.degree. C. at a rate of
about 0.3.degree. C. to about 1.5.degree. C. per minute.
30. The collagen powder of claim 21, wherein step (c) comprises at
least one equilibrating step, and wherein the at least one
equilibrating step comprises maintaining the temperature at a
constant temperature, sufficient to allow the frozen collagen to
reach a desired temperature.
31. The collagen powder of claim 21, wherein step (c) comprises six
equilibrating steps, each equilibrating step being conducted when
the temperature is increased by 10.degree. C., and wherein step (c)
comprises freezing to a temperature of about -33.degree. C. to
about -42.degree. C.
32. The collagen powder of claim 21, wherein step (c) comprises at
least one equilibrating step, and wherein the at least one
equilibrating step comprises maintaining the temperature at a
constant temperature, sufficient to allow the frozen collagen to
reach a desired temperature.
33. The collagen powder of claim 21, wherein step (c) comprises six
equilibrating steps, each equilibrating step being conducted when
the temperature is increased by 10.degree. C.
34. The collagen powder of claim 21, wherein step (d) comprises
milling the freeze-dried collagen to a powder using a mesh size of
1 mm.
35. The collagen powder of claim 21, wherein in step (c), an amount
of water substance removed is about 30 times an amount of collagen
in the adjusted collagen.
36. The collagen powder of claim 21, wherein the method further
comprises sterilizing the collagen powder obtained at step (d)
using ethylene oxide.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to a collagen powder, a method
of manufacture thereof, and uses thereof.
BACKGROUND TO THE INVENTION
[0002] Processes for the preparation of collagen-based powders for
use in human and veterinary medicine are well known in the art. One
important performance characteristic of collagen powders is the
ability to absorb fluids, such as blood and/or wound exudate. Given
that collagen powders often show low density, optimized processing
characteristics are also of paramount importance.
[0003] Commonly, the collagen used for subsequent preparation of
the collagen-based powders is first isolated by extraction from
mammalian hide or tendon, purified, enzymatically-treated to remove
non-helical telopeptides, partially solubilised with acid, and
finally precipitated by increasing the pH to provide a source of
purified, fibrillar collagen. Once isolated, the collagen source
may be further processed for the manufacture of collagen-based
materials immediately, or is otherwise stored while waiting further
processing. For storage convenience at commercial scale, the
collagen source is normally concentrated by removal of water using
centrifugation to reduce bulk and thereby create a wet mass. The
wet mass must be stored frozen to preserve the collagen and prevent
bacterial growth. When needed for manufacture of collagen-based
powders, the frozen collagen wet mass is typically thawed and
redispersed. Whether the isolated collagen is used immediately or
frozen and thawed as a wet mass, the collagen source is generally
viscous and difficult to process at commercial scale into
collagen-based powders.
[0004] It is known to prepare collagen powders by milling
pre-formed collagen sponge products. Disadvantageously, this known
method results in collagen powders having low density. Moreover, a
large number of collagen sponges must be formed in order to prepare
a sufficient amount of collagen powder, which makes the collagen
powder preparation process inefficient, particularly given that the
amount of water that needs to be removed during the preparation
process can be approximately 200-fold greater than the equivalent
dry mass of the collagen source. In addition, the resulting
collagen powder is difficult to further process because it exhibits
undesirable processing characteristics, such as poor flow behaviour
and high electrostatic charge properties. These material properties
also lead to difficulties in the application of the resulting
collagen powder, for example, for use in woundcare or implantation.
Due to the low density of the resulting collagen powder, it can
easily be blown away by minor air movements and adheres to
surfaces, which can complicate placement of the collagen powder at
the site of application.
[0005] There is a need to provide a collagen powder having
desirable product characteristics, such as high fluid absorption
capacity, while also having processing characteristics that allow
commercial manufacturing and handling of the collagen powder.
SUMMARY OF THE INVENTION
[0006] According to a first aspect of the present invention, there
is provided a process for preparing a collagen powder, the process
comprising the steps of: [0007] (a) providing a collagen source;
[0008] (b) adjusting the collagen source to a concentration of
1.5-4.0%; [0009] (c) adjusting the collagen source to a pH of
3.5-5.0; [0010] (d) freezing the collagen source; [0011] (e)
dehydrating the frozen collagen; and [0012] (f) degrading the
dehydrated collagen to a powder.
[0013] Optionally, the concentration-adjusting step (b) is
performed prior to the pH-adjusting step (c). Alternatively, the
pH-adjusting step (c) is performed prior to the
concentration-adjusting step (b). Further alternatively, the
concentration-adjusting step (b) and the pH-adjusting step (c) are
performed simultaneously.
[0014] Optionally, the collagen source in the providing step (a) is
fibrillar collagen. Further optionally, the collagen source in the
providing step (a) is selected from Type I collagen, Type II
collagen, Type III collagen, and a mixture thereof. Still further
optionally, the collagen source in the providing step (a) is Type I
collagen.
[0015] Optionally, the collagen source in the providing step (a)
has a collagen concentration of greater than 4.0%. Further
optionally, the collagen source in the providing step (a) has a
collagen concentration of greater than 15.0%. Still further
optionally, the collagen source in the providing step (a) has a
collagen concentration of greater than 30.0%.
[0016] Optionally, the collagen source in the providing step (a)
has a pH greater than 5.0. Further optionally, the collagen source
in the providing step (a) has a collagen concentration of 7.0.
Still further optionally, the collagen source in the providing step
(a) has a collagen concentration of greater than 7.0.
[0017] Optionally, the process comprises the additional step of
mechanically degrading the collagen source prior to the freezing
step (d). Further optionally, the process comprises the additional
step of homogenising the collagen source prior to the freezing step
(d). Still further optionally, the process comprises the additional
step of shear mixing the collagen source prior to the freezing step
(d).
[0018] Optionally, the additional mechanical degrading step is
conducted after the concentration-adjusting step (b) and/or the
pH-adjusting step (c); and prior to the freezing step (d).
[0019] Optionally, the additional mechanical degrading step is
conducted for a period of more than 5 seconds. Further optionally,
the additional mechanical degrading step is conducted for a period
of 5-900 seconds. Still further optionally, the additional
mechanical degrading step is conducted for a period of 5-900
seconds until a homogenous collagen dispersion is formed.
[0020] Optionally, the concentration-adjusting step (b) comprises
introducing a fluid to the collagen source. Further optionally, the
concentration-adjusting step (b) comprises introducing an aqueous
fluid to the collagen source. Still further optionally,
concentration-adjusting step (b) comprises introducing water,
optionally purified water, to the collagen source.
[0021] Optionally, the collagen source is adjusted to an equivalent
concentration of 1.5-4.0% (w/w) dry collagen. Further optionally,
the collagen source is adjusted to an equivalent concentration of
2.0-3.5% (w/w) dry collagen.
[0022] Optionally, the process comprises the step (c) of adjusting
the collagen source to a pH of less than 4.5. Further optionally,
the process comprises the step (c) of adjusting the collagen source
to a pH of 3.8-4.3. Still further optionally, the process comprises
the step (c) of adjusting the collagen source to a pH of 4.0.
[0023] Optionally, the pH-adjusting step (c) comprises introducing
an acid to the collagen source. Further optionally, the
pH-adjusting step (c) comprises introducing an acid solution to the
collagen source. Still further optionally, the pH-adjusting step
(c) comprises introducing an aqueous acid solution to the collagen
source.
[0024] Optionally, the pH-adjusting step (c) comprises introducing
a carboxylic acid to the collagen source. Further optionally, the
pH-adjusting step (c) comprises introducing a carboxylic acid
solution to the collagen source. Still further optionally, the
pH-adjusting step (c) comprises introducing an aqueous carboxylic
acid solution to the collagen source.
[0025] Optionally, the pH-adjusting step (c) comprises introducing
a sulfonic acid to the collagen source. Further optionally, the
pH-adjusting step (c) comprises introducing a sulfonic acid
solution to the collagen source. Still further optionally, the
pH-adjusting step (c) comprises introducing an aqueous sulfonic
acid solution to the collagen source.
[0026] Optionally, the pH-adjusting step (c) comprises introducing
a mineral acid to the collagen source. Further optionally, the
pH-adjusting step (c) comprises introducing a mineral acid solution
to the collagen source. Still further optionally, the pH-adjusting
step (c) comprises introducing an aqueous mineral acid solution to
the collagen source.
[0027] Optionally, the pH-adjusting step (c) comprises introducing
acetic add to the collagen source. Further optionally, the
pH-adjusting step (c) comprises introducing an acetic acid solution
to the collagen source. Still further optionally, the pH-adjusting
step (c) comprises introducing an aqueous acetic add solution to
the collagen source.
[0028] Optionally, pH-the adjusting step (c) comprises introducing
anhydrous acetic acid to the collagen source.
[0029] Optionally, the concentration-adjusting step (b) and the
pH-adjusting step (c) can be conducted simultaneously by
introducing an acid solution, optionally an aqueous acid solution,
to the collagen source.
[0030] Optionally, the concentration-adjusting step (b) and the
pH-adjusting step (c) can be conducted simultaneously by
introducing an acetic acid solution, optionally an aqueous acetic
acid solution, to the collagen source.
[0031] Optionally, the concentration-adjusting step (b) is
conducted for a period of not less than 0.5 hours. Further
optionally, the concentration-adjusting step (b) is conducted for a
period of 0.5 hours.
[0032] Optionally, the pH-adjusting step (c) is conducted for a
period of 1-180 minutes.
[0033] Optionally, the concentration-adjusting step (b) and the
pH-adjusting step (c) are conducted simultaneously for a period of
more than 1 minute. Further optionally, the concentration-adjusting
step (b) and the pH-adjusting step (c) are conducted simultaneously
for a period of 1-180 minutes.
[0034] Optionally, the freezing step (d) comprises freezing to a
temperature of about -33.degree. C. to about -42.degree. C. Further
optionally, the freezing step (d) comprises freezing to a
temperature of about -38.degree. C. Still further optionally, the
freezing step (d) comprises freezing at a rate of about 0.3.degree.
C. to about 1.5.degree. C. per minute, optionally a rate of about
0.5.degree. C. per minute.
[0035] Optionally, the dehydrating step (e) comprises removing the
aqueous phase. Further optionally, the dehydrating step (e)
comprises removing the aqueous phase by reducing the pressure.
Still further optionally, the dehydrating step (e) comprises
removing the aqueous phase by reducing the pressure to about 0.05
to about 1 mbar. Still further optionally, the dehydrating step (e)
comprises removing the aqueous phase by applying at least a partial
vacuum, optionally by applying a vacuum.
[0036] Optionally or additionally, the dehydrating step (e)
comprises increasing the temperature. Further optionally or
additionally, the dehydrating step (e) comprises increasing the
temperature under vacuum or partial vacuum. Still further
optionally or additionally, the dehydrating step (e) comprises
increasing the temperature to at least +30.degree. C. Still further
optionally or additionally, the dehydrating step (e) comprises
increasing the temperature to at least +30.degree. C. under vacuum
or partial vacuum. Still further optionally or additionally, the
dehydrating step (e) comprises increasing the temperature to at
least +40.degree. C. Still further optionally or additionally, the
dehydrating step (e) comprises increasing the temperature to at
least +40.degree. C. under vacuum or partial vacuum.
[0037] Optionally or additionally, the dehydrating step (e)
comprises increasing the temperature to about +30.degree. C. at a
rate of about 0.3.degree. C. to about 1.5.degree. C. per minute,
further optionally at a rate of about 0.5.degree. C. per minute.
Further optionally or additionally, the dehydrating step (a)
comprises increasing the temperature of the collagen to about
+30.degree. C. at a rate of about 0.3.degree. C. to about
1.5.degree. C. per minute, further optionally at a rate of about
0.5.degree. C. per minute, under vacuum or partial vacuum.
[0038] Optionally or additionally, the dehydrating step (e)
comprises increasing the temperature to about +40.degree. C. at a
rate of about 0.3.degree. C. to about 1.5.degree. C. per minute,
further optionally at a rate of about 0.5.degree. C. per minute.
Further optionally or additionally, the dehydrating step (e)
comprises increasing the temperature of the collagen to about
+40.degree. C. at a rate of about 0.3.degree. C. to about
1.5.degree. C. per minute, further optionally at a rate of about
0.5.degree. C. per minute, under vacuum or partial vacuum.
[0039] Optionally, the dehydrating step (e) comprises at least one
equilibrating step.
[0040] Optionally, the at least one equilibrating step comprises
maintaining the temperature at a constant temperature, sufficient
to allow the frozen collagen to reach a desired temperature.
Further optionally, the at least one equilibrating step comprises
maintaining the temperature at a constant temperature for a
sufficient period of time to allow the frozen collagen to reach a
desired temperature. Still further optionally, the at least one
equilibrating step comprises maintaining the temperature at a
constant temperature for at least 10 mins, optionally at least 20
mins, further optionally at least 30 mins, still further optionally
at least 45 mins, still further optionally at least 60 mins; to
allow the frozen collagen to reach a desired temperature.
[0041] Optionally, the at least one equilibrating step is conducted
when the temperature is increased to at least -20.degree. C.
Optionally or additionally, the at least one equilibrating step is
conducted when the temperature is increased to at least -10.degree.
C. Optionally or additionally, the at least one equilibrating step
is conducted when the temperature is increased to at least
0.degree. C. Optionally or additionally, the at least one
equilibrating step is conducted when the temperature is increased
to at least +10.degree. C. Optionally or additionally, the at least
one equilibrating step is conducted when the temperature is
increased to at least +20.degree. C. Optionally or additionally,
the at least one equilibrating step is conducted when the
temperature is increased to at least +30.degree. C. Optionally or
additionally, the at least one equilibrating step is conducted when
the temperature is increased to at least +40.degree. C.
[0042] Optionally, the dehydrating step (e) comprises six
equilibrating steps, each equilibrating step being conducted when
the temperature is increased by about 10.degree. C. Further
optionally, the dehydrating step (e) comprises six equilibrating
steps, each equilibrating step being conducted when the temperature
is increased to about -20.degree. C., about -10.degree. C., about
0.degree. C., about +10.degree. C., about +20.degree. C., and about
+30.degree. C.
[0043] Optionally, the collagen source can be formed into collagen
layers prior to the freezing step (d).
[0044] Optionally, the collagen dispersion can be filled into
moulds to form collagen layers prior to the freezing step (d).
Further optionally, the collagen dispersion can be filled into
moulds to form collagen layers having an average thickness of 1-5
mm prior to the freezing step (d). Still further optionally, the
collagen dispersion can be filled into moulds to form collagen
layers having an average thickness of 1-3 mm prior to the freezing
step (d). Still further optionally, the collagen dispersion can be
filled into moulds having an average thickness of 1-5 mm and
dimensions of 50.times.40 cm to form collagen layers prior to
either or both of the freezing step (d) and the dehydrating step
(e).
[0045] Optionally, the degrading step (f) comprises mechanically
degrading the dehydrated collagen to a powder. Further optionally,
the degrading step (f) is selected from milling, cutting, grinding,
granulating, and a mixture thereof. Still further optionally, the
degrading step (f) comprises milling the dehydrated collagen to a
powder. Still further optionally, the degrading step (f) comprises
milling the dehydrated collagen to a powder using a mesh size of 1
mm.
[0046] Optionally, the collagen powder is filled into a
container.
[0047] Optionally, the collagen powder is sterilized. Further
optionally, the collagen powder is sterilized after being filled
into a container.
BRIEF DESCRIPTION OF E DRAWINGS
[0048] Embodiments of the invention will now be described by way of
non-limiting examples, and with reference to the accompanying
drawings, in which:
[0049] FIG. 1 is a graph illustrating water uptake of collagen
powders prepared at different pH and collagen concentrations;
and
[0050] FIG. 2 is a graph illustrating bulk density of collagen
powders prepared at different pH and collagen concentrations.
EXAMPLES
Example 1
Manufacturing Process
[0051] Collagen can be isolated from a number of sources, for
example, animal hides and animal tendons. In a preferred
embodiment, the collagen is isolated from animal tendon, for
example equine or bovine tendon; although any known source of
collagen, including fibrous tissue, optionally connective tissue,
may be used and selected by one skilled in the art. Preferably, the
collagen is isolated from equine tendon. In the method of
isolation, equine tendons were milled to degrade the collagen
source. The milled equine tendons were treated with a number of
reagents, including 1N sodium hydroxide (NaOH) to remove
microbiological contamination such as prions at the beginning of
the process. Treatment steps with hydrogen peroxide and washing
steps at different pH values were conducted, followed by a milling
step, which was used to increase the surface for the next treatment
step. The molecular weight of the collagen source was additionally
reduced by treatment with the proteolytic enzyme pepsin at an
approximate pH of 2.5. The pH was adjusted using an aqueous
solution of 1N HCl. The pepsin was used to degrade contaminating
serum components such as equine serum albumin (ESA) and resulted in
the detachment of non-helical portions of the collagen molecule
(telopeptides). During this process, the collagen material was also
partially solubilised in the acidic medium. After filtration, the
pH level was increased from 2.5 to 7.5 by addition of 1N sodium
hydroxide (NaOH). This pH adjustment resulted in precipitation of
the fibrillar collagen out of solution, which was then concentrated
by means of centrifugation to provide a collagen dispersion having
a concentration of about 3-30% (w/w). The resulting material was
designated fresh collagen. The fresh collagen can be processed in
several ways.
[0052] The fresh collagen can be packaged in suitable portions and
frozen to -20.degree. C. to be stored in a freezer until required
for use. The resulting material was designated frozen collagen. The
frozen collagen is thawed prior to use in the same manner as fresh
collagen.
[0053] An amount of 63.3 g of frozen collagen source having an
equivalent concentration of 28.4% dry content was thawed to room
temperature and provided in a suitably sized stainless steel
container. An amount of 20 g of 1N acetic acid was introduced to
the collagen source to adjust the pH to 4.2. Purified water was
introduced to the collagen dispersion to disperse the collagen
source to a concentration of 1.5-4.0%.
[0054] After 5 minutes of soaking, a non-homogeneous semi-solid
collagen dispersion was obtained and transferred into a cutting
device (Heavy Duty Blender 39BL10, Waring Laboratory Services,
Winsted, Conn., USA). The collagen dispersion was homogenized for a
short period of time (5 seconds to 15 minutes) until a uniform
semi-solid collagen dispersion with homogeneously hydrated and
swollen collagen was obtained. The viscous collagen dispersion was
weighed in amounts of 280 g onto suitable moulds or trays, for
example stainless steel trays or large blister moulds with a size
of 32.times.22 cm, and distributed to obtain a collagen layer
having a thickness of 1-5 mm.
[0055] The distributed collagen dispersion was placed into a freeze
dryer (Christ Epsilon I 15), where it was first frozen and then
dehydrated under vacuum by sublimation. The freezing and
dehydrating conditions include chamber pressures between 50 and 500
.mu.bar, and shelf temperatures that start at about -40.degree. C.
and are sequentially increased to +40.degree. C. Typically, the
freeze drying process (the freezing and dehydrating steps) has a
total duration time of 18-30 hours. When the collagen is
dehydrated, the freeze dryer chamber is brought to atmospheric
pressure. The resultant collagen is in the form of collagen layers
with slightly lower thickness than in the collagen dispersion layer
(for example, the resultant collagen is in the form of collagen
layers having a thickness of 1-4 mm).
[0056] The collagen layers were cut using scissors to units with
dimensions that allow suitable feeding into a mill (Retsch ZM 100),
for example layers having dimensions 1.times.1 cm, or 10.times.10
cm, depending on the milling equipment. For the Retsch ZM 100 mill,
the collagen layers were cut using scissors to layers having
dimensions 0.5.times.0.5 cm. The cut collagen layers were collected
in a stainless steel container and milled, for example using an
ultracentrifugal mill (Retsch ZM 100 at 18000 rpm at room
temperature) with a mesh size of 1 mm using air cooling. The
degraded collagen powder is collected and filled into polyethylene
(polythene; PE) containers or bags for intermediary storage.
[0057] Subsequently, the collagen powder was a quoted into final
packaging configuration of 5 g per unit, optionally sterilized
using ethylene oxide (EO) gas, and tested as described in Example
2.
Example 2
Analytical Characterization (Water Uptake)
[0058] Fluid absorption (water uptake) capacity of non-sterile
collagen powder was tested by soaking a defined mass of 100-500 mg
of collagen powder in purified water for a defined period of time
(for example, 5 minutes); removing excess surface water by placing
a sieve flat onto a tissue for 10 seconds and weighing the hydrated
sample. The water uptake was analyzed under consideration of the pH
and collagen concentration in the mixture prior to the freezing and
dehydrating steps.
[0059] The pH of the collagen dispersion prior to the freezing and
dehydrating steps strongly influenced the fluid absorption
capacity. The water uptake is shown in FIG. 1 in dependence of pH
of the collagen dispersion prior to the freezing and dehydrating
steps. The concentration of the collagen dispersion is indicated by
the area of the circles. The collagen powder prepared by the
process of the present invention is shown at pH 3.5-5.0 and having
collagen concentrations of 1.5-5.0%. Collagen powders having a
lower collagen concentration exhibited comparable water uptake, but
poor processing characteristics. The water uptake properties appear
to be primarily defined by the pH; and a pH of <4.5 appears to
provide a water absorption value of at least 20-fold greater than
the sample weight.
[0060] A direct comparative test was conducted between a collagen
powder prepared by the process according to the present invention,
and sterile samples of two commercially available products. In each
case, the water uptake was determined using the method described
herein above.
[0061] A microfibrillar collagen hemostat (MCH), indicated for all
surgical procedures including neurosurgery and urology, available
from Davol, a Bard Company (RI, USA), and known as Avitene.TM.
Flour MCH; exhibited a water uptake of 6.5-fold greater than the
sample weight tested.
[0062] A collagen powder made of sterile (gamma-irradiated),
native, bioabsorbable bovine corium collagen, manufactured by
Holphar Arzneimittel, von Fournier Pharma GmbH (Sulzbach, Germany)
and known as PANGEN.TM. Puder exhibited a water uptake of 9.2-fold
greater than the sample weight tested.
[0063] For both commercially-sourced products tested, the water
uptake is significantly lower than for the collagen powder prepared
according to the process of the present invention.
Example 3
Analytical Characterization (Bulk Density)
[0064] The bulk density of collagen powders was determined by
filling a weighed amount of collagen powder (e.g. 1 g) into a
graduated cylinder and determining the volume (e.g. 10-50 mL). The
bulk density significantly increased with a higher collagen
concentration in the collagen dispersion prior to the freezing and
dehydrating steps.
[0065] Collagen powder prepared according to the process of the
present invention exhibited bulk density values of 20-30
mg/cm.sup.3 compared to collagen powders having a lower collagen
concentration, which exhibited bulk density values of approximately
4 mg/cm.sup.3.
[0066] The relationship between the pH of the collagen dispersion,
the concentration of the collagen dispersion; and the bulk density
is shown in FIG. 2. The bulk density appears to be influenced by
the collagen concentration.
[0067] The present invention therefore provides a collagen powder
having an improved bulk density, improved processing
characteristics, and increased fluid uptake.
[0068] The process of preparation according to the present
invention also provides a preparation process having improved
efficiency by removing the amount of water that needs to be removed
during the preparation process (the amount of water that needs to
be removed in the process of preparation according to the present
invention is approximately 30-fold greater than the mass of
collagen compared to 200-fold greater than the mass of collagen of
known methods). This allows reduction of process time and increased
throughput.
* * * * *