U.S. patent application number 15/406084 was filed with the patent office on 2017-05-11 for biodegradable implant and method for manufacturing same.
The applicant listed for this patent is U&I Corporation. Invention is credited to Sung-Youn Cho, Jong-Tack Kim, Yu-Chan Kim, Ja-Kyo Koo, Hyun-Kwang Seok, Seok-Jo Yang.
Application Number | 20170128620 15/406084 |
Document ID | / |
Family ID | 43011631 |
Filed Date | 2017-05-11 |
United States Patent
Application |
20170128620 |
Kind Code |
A1 |
Koo; Ja-Kyo ; et
al. |
May 11, 2017 |
BIODEGRADABLE IMPLANT AND METHOD FOR MANUFACTURING SAME
Abstract
This invention relates to a biodegradable implant including
magnesium, wherein the magnesium contains, as impurities, (i)
manganese (Mn); and (ii) one selected from the group consisting of
iron (Fe), nickel (Ni) and mixtures of iron (Fe) and nickel (Ni),
wherein the impurities satisfy the following condition:
0<(ii)/(i).ltoreq.5, and an amount of the impurities is 1 part
by weight or less but exceeding 0 parts by weight based on 100
parts by weight of the magnesium, and to a method of manufacturing
the same.
Inventors: |
Koo; Ja-Kyo; (Seoul, KR)
; Seok; Hyun-Kwang; (Seoul, KR) ; Yang;
Seok-Jo; (Daegu, KR) ; Kim; Yu-Chan; (Seoul,
KR) ; Cho; Sung-Youn; (Uijeongbu-Si, KR) ;
Kim; Jong-Tack; (Jeonju-Si, KR) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
U&I Corporation |
Gyeonggi-do |
|
KR |
|
|
Family ID: |
43011631 |
Appl. No.: |
15/406084 |
Filed: |
January 13, 2017 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14824644 |
Aug 12, 2015 |
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15406084 |
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13265694 |
Oct 21, 2011 |
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PCT/KR10/02542 |
Apr 22, 2010 |
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14824644 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61L 27/48 20130101;
B22F 3/1121 20130101; B22F 2998/10 20130101; B22F 7/06 20130101;
C22F 1/06 20130101; A61L 27/047 20130101; A61L 27/427 20130101;
B22F 3/26 20130101; C22C 23/02 20130101; A61L 27/58 20130101; A61L
27/446 20130101; A61L 27/42 20130101; C22C 23/00 20130101; Y10T
29/49 20150115; A61L 27/56 20130101 |
International
Class: |
A61L 27/04 20060101
A61L027/04; A61L 27/56 20060101 A61L027/56; B22F 7/06 20060101
B22F007/06; B22F 3/11 20060101 B22F003/11; B22F 3/26 20060101
B22F003/26; A61L 27/58 20060101 A61L027/58; C22C 23/00 20060101
C22C023/00 |
Foreign Application Data
Date |
Code |
Application Number |
Apr 22, 2009 |
KR |
10-2009-0035267 |
Claims
1-25. (canceled)
26. A method of manufacturing a biodegradable implant, comprising:
i) providing a magnesium alloy represented by Chemical Formula 1
below comprising based on total weight thereof, from 4.51 wt % to
10.8 wt % of Ca; from 0.1 to 5 wt % of X, and a remainder of Mg;
and ii) forming the magnesium alloy: Mg--Ca--X <Chemical Formula
1> wherein X is Mn or Zn.
27. The method of claim 26, wherein i) comprises: i-1) preparing a
porous structure; and i-2) filling pores of the porous structure
with the magnesium alloy.
28. The method of claim 26, wherein ii) is performed using one or
more selected from the group consisting of cooling, extrusion, and
metal processing.
29-36. (canceled)
Description
TECHNICAL FIELD
[0001] The present invention relates to a biodegradable implant and
a method of manufacturing the same, and more particularly to a
biodegradable implant, whose biodegradation rate is easily
controlled, the strength and an interfacial force to bone tissue of
which are high, in which a rate of bone formation is increased, and
that has simultaneously improved corrosion resistance and
mechanical properties, and to a method of manufacturing the
same.
BACKGROUND ART
[0002] Typical materials used in implants to be used in medical
treatment include metal, ceramic and polymer. Among these, metallic
implants have superior mechanical properties and processability.
However, metallic implants are disadvantageous because of stress
shielding, image degradation and implant migration. Also, ceramic
implants have superior biocompatibility compared to the other
implants. However, ceramic implants are easily broken by external
impact, and are difficult to process. Also, polymeric implants have
relatively weak strength compared to the other implant
materials.
[0003] Recently, porous implants are being developed which may
accelerate the formation of bone tissue upon insertion into the
human body and may decrease Young's modulus to prevent stress
shielding. However, such porous implants have low mechanical
strength and are weak to external impact. Also, research and
development is being carried out into biodegradable implants which
need not be removed after being inserted into the human body to
achieve their desired purpose. The study of medical applications
using such a biodegradable material has already begun since the
middle of the 1960s and is mainly focused on using polymers such as
polylactic acids (PLA), polyglycolic acid (PGA) or a copolymer
thereof including PLGA. However, biodegradable polymers have low
mechanical strength, produce acids upon decomposition, and have the
disadvantage that it is difficult to control their biodegradation
rate, and thus they have limited applications. In particular, the
biodegradable polymers are difficult to apply to orthopedic
implants that have to withstand a strong load or dental implants
because of the properties of polymers having low mechanical
strength. Hence, some biodegradable materials are being studied to
overcome the problems of the biodegradable polymers. Typical
examples thereof include ceramic such as tri-calcium phosphate
(TCP), combination materials of biodegradable polymer and
biodegradable hydroxyapatite (HA), etc.
[0004] However, mechanical properties of such materials are not
much higher than those of biodegradable polymers. In particular,
poor impact resistance of the ceramic material is regarded as very
disadvantageous in a biomaterial. Also, the actual usability of
such materials is open to question, because it is difficult to
control the biodegradation rate.
[0005] Meanwhile, biodegradable implants should be very strong
because part or all of it have to withstand a load when used into
the human body. In order to ensure high strength, a biodegradable
implant is further subjected to additional processes including
rapid cooling, extrusion, and heat treatment so that the framework
of the implant is made fine and internal residual stress should be
controlled. Also, the alloy composition of a metal used for a
biodegradable implant should be appropriately designed by changing
constituent elements or content thereof. As such, changing the
alloy composition may be typically performed by adjusting the
amounts of the elements that are added. As the amounts of elements
added to the alloy increase, mechanical strength is enhanced.
[0006] However, when the amounts of added elements are increased,
the metal for the implants may easily create a galvanic circuit
that increases the corrosion rate attributable to an increase in
the non-uniformity of the composition thereof and the
non-uniformity of a fine framework, undesirably increasing the
corrosion rate of implants. Hence, it is very difficult to design
alloy materials which have high strength and low biodegradation
rate to be applied to implants.
DISCLOSURE
Technical Problem
[0007] Accordingly, the present invention has been made keeping in
mind the above problems occurring in the related art, and an object
of the present invention is to provide a biodegradable implant
whose biodegradation rate may be controlled.
[0008] Another object of the present invention is to provide a
biodegradable implant which may overcome problems of conventional
porous implants such as low mechanical strength and poor impact
resistance.
[0009] A further object of the present invention is to provide a
biodegradable implant whose corrosion resistance and mechanical
properties have been simultaneously improved.
[0010] Still a further object of the present invention is to
provide a biodegradable implant in which a rate of bone formation
may be increased, and with the passing of a predetermined period of
time after surgery, a biodegradable metal material charged in pores
has disappeared and an osseous replacement has taken place.
Technical Solution
[0011] In order to accomplish the above objects, an aspect of the
present invention provides a biodegradable implant comprising
magnesium, wherein the magnesium contains as impurities (i)
manganese (Mn); and (ii) one selected from the group consisting of
iron (Fe), nickel (Ni) and mixtures of iron (Fe) and nickel (Ni),
wherein the impurities satisfy the following condition:
0<(ii)/(i).ltoreq.5, and an amount of the impurities is 1 part
by weight or less but exceeding 0 parts by weight based on 100
parts by weight of the magnesium.
[0012] In addition, another aspect of the present invention
provides a method of manufacturing a biodegradable implant,
comprising a) providing magnesium containing as impurities (i)
manganese (Mn); and (ii) one selected from the group consisting of
iron (Fe), nickel (Ni) and mixtures of iron (Fe) and nickel (Ni),
wherein the impurities satisfy the following condition:
0<(ii)/(i).ltoreq.5, and an amount of the impurities is 1 part
by weight or less but exceeding 0 parts by weight based on 100
parts by weight of the magnesium; and b) forming the magnesium.
[0013] In addition, another aspect of the present invention
provides a biodegradable implant, comprising a magnesium alloy
represented by Chemical Formula 1 below comprising based on the
total weight thereof, 23 wt % or less but exceeding 0 wt % of Ca;
10 wt % or less but exceeding 0 wt % of X; and a remainder of
Mg:
Mg--Ca--X <Chemical Formula 1>
[0014] wherein X is Mn or Zn
[0015] In addition, another aspect of the present invention
provides a method of manufacturing a biodegradable implant,
comprising i) providing the magnesium alloy; and ii) forming the
magnesium alloy.
[0016] In addition, another aspect of the present invention
provides a method of manufacturing a biodegradable implant,
comprising applying ultrasound to the biodegradable implant
comprising magnesium.
[0017] In addition, another aspect of the present invention
provides a biodegradable implant, comprising, based on the total
weight thereof, 10 wt % or less but exceeding 0 wt % of manganese;
1 wt % or less but exceeding 0 wt % of iron; and a remainder of a
metal comprising magnesium.
[0018] In addition, another aspect of the present invention
provides a biodegradable implant, comprising, based on the total
weight thereof, 90 wt % or less but exceeding 0 wt % of magnesium
oxide (MgO); and a remainder of a metal comprising magnesium.
Advantageous Effects
[0019] According to the present invention, a biodegradable implant
can be advantageously present for a long period of time in vivo
because its biodegradation rate is controlled to be very low.
[0020] Also according to the present invention, in the case where
the biodegradable implant includes a porous structure, blood
vessels that pass through pores are formed, thus increasing the
rate of bone formation and decreasing Young's modulus thereby
reducing stress shielding.
[0021] Also according to the present invention, the biodegradable
implant can have enhanced mechanical strength and impact
resistance.
[0022] Also according to the present invention, the biodegradable
implant can be simultaneously improved in terms of corrosion
resistance and mechanical properties.
[0023] Thus, the implant according to the present invention is
adapted to be used in bone replacements or treatment for bone, and
can be used for orthopedics, dental care, plastic surgery or blood
vessels.
DESCRIPTION OF DRAWINGS
[0024] FIG. 1 is a graph showing the hydrogen evolution amount in
relation to the immersion time of the implant samples of Example 1
and 2 and Comparative Examples 1;
[0025] FIG. 2 is a graph showing results of evaluating mechanical
strength of the implant samples of Examples 3 and 4 and Comparative
Example 3 before extrusion;
[0026] FIG. 3 is a graph showing results of evaluating mechanical
strength of the implant samples of Examples 3 and 4 and Comparative
Example 3 after extrusion;
[0027] FIG. 4 is a graph showing the hydrogen evolution rate in
relation to the immersion time of the implant samples of Examples 3
and 4 and Comparative Example 3;
[0028] FIG. 5 is a graph showing the hydrogen evolution rate in
relation to the immersion time of the implant samples of Examples 4
to 6.
[0029] FIG. 6 is a graph showing the hydrogen evolution amount in
relation to the immersion time of the implant samples of Examples 7
to 11 and Comparative Examples 2 and 4;
[0030] FIG. 7 is a graph showing the hydrogen evolution amount in
relation to Zn content;
[0031] FIG. 8 is an electron microscope image showing the surface
of the implant sample of Example 7 immersed in abiomimetic solution
for 61 hours;
[0032] FIG. 9 is an image showing the surface of the implant sample
of Example 7 immersed in a biomimetic solution for 61 hours as
analyzed using EDS;
[0033] FIG. 10 is an image showing the implant sample of Example 7
which is immersed in a biomimetic solution for 61 hours and from
which a corrosion material was removed;
[0034] FIG. 11 is an image showing the cross-section of the implant
sample of Example 7 immersed in a biomimetic solution for 61
hours;
[0035] FIG. 12 is an enlarged image of the image of FIG. 11;
[0036] FIG. 13 is of WDS (JXA-8500F, available from JEOL) images
showing the implant sample of Example 7 immersed in a biomimetic
solution for 61 hours;
[0037] FIG. 14 is an image showing the cross-section of the implant
sample of Example 8 immersed in abiomimetic solution for 61
hours;
[0038] FIG. 15 is of WDS (JXA-8500F, available from JEOL) images
showing the implant sample of Example 8 immersed in a biomimetic
solution for 61 hours;
[0039] FIG. 16 is a graph showing the hydrogen evolution rate in
relation to the immersion time in two implant samples of Example 8
one of which is treated with ultrasound and the other one of which
is not treated with ultrasound after which they are immersed in a
biomimetic solution;
[0040] FIG. 17 is a graph showing the hydrogen evolution amount in
relation to the immersion time in the implant sample of Example 8
treated with ultrasound and then immersed in a biomimetic
solution;
[0041] FIG. 18 is a graph showing the hydrogen evolution amount in
relation to the immersion time of the implant samples of Examples
12.about.14;
[0042] FIG. 19 is of images showing the size of crystal grains of
the implant sample of Example 14 before extrusion;
[0043] FIG. 20 is a graph showing the hydrogen evolution amount in
relation to the immersion time before and after extrusion of the
implant sample of Example 14; and
[0044] FIG. 21 is a photograph showing swelling due to the
generation of hydrogen gas in a rat into which the implant sample
of Comparative Example 4 is inserted.
BEST MODE
[0045] Hereinafter, a detailed description will be given of the
present invention.
[0046] I. Biodegradable Implant Containing Impurities
[0047] According to the present invention, a biodegradable implant
comprises magnesium (Mg), wherein the Mg contains, as impurities
(i) Mn and (ii) one selected from the group consisting of Fe, Ni
and mixtures of Fe and Ni, wherein the impurities satisfy the
following condition: 0<(ii)/(i)'5, and an amount of the
impurities is 1 part by weight or less but exceeding 0 parts by
weight based on 100 parts by weight of the magnesium.
[0048] Preferably, the impurities satisfy the following condition:
0<(ii)/(i).ltoreq.0.5. If the impurities satisfy the condition,
the biodegradation rate is controlled to be maximally low thus
increasing corrosion resistance. Thereby, implants may be present
for a longer period of time in vivo.
[0049] When Ni and Mn are contained in the impurities, Ni causes an
allergic reaction in the human body and increases the corrosion
rate of pure Mg. Hence, Ni content is preferably 100 ppm or less,
and more preferably 50 ppm or less.
[0050] Also, the Mg may further include aluminum (Al) as an
impurity.
[0051] According to the present invention, there may be provided a
biodegradable implant resulting from charging Mg containing the
above impurities in the pores of a porous structure.
[0052] The pores of the porous structure preferably have a size of
200.about.500 .mu.m, and the pore size may be adjusted depending on
the application field using methods typically used in the art. If
the pore size falls within the above range, it is easy to allow
blood vessels responsible for supplying nutrients, minerals and
ions to pass through the pores.
[0053] The porous structure may have a porosity of 5.about.95%. The
porosity means a volume ratio of pores relative to total volume. In
the case where the strength required of a target is high, the
porosity may be decreased so that the strength of a porous
structure is enhanced. For example, the case where a porous
structure is made of tantalum having high strength or merely
functions to fill the cavities of lost bone, high porosity thereof
does not cause problems.
[0054] The porous structure may comprise one or more selected from
the group consisting of a metal, a ceramic, and a polymer. In the
case where the porous structure is made of a metal, one or more
selected from the group consisting of titanium or a titanium alloy,
a cobalt-chromium alloy and stainless steel may be used. In the
case where the porous structure is made of a ceramic, one or more
selected from the group consisting of calcium phosphate, alumina,
zirconia and magnesia may be used. In the case where the porous
structure is made of a polymer, one or more selected from the group
consisting of polyethylene, polylactic acids (PLA), polyglycolic
acid (PGA) and a copolymer thereof including PLGA may be used. As
such, in the case where the porous structure may comprise the above
polymer, an acid that is biodegradable is generated so that the pH
may decrease. In the case of a polymer composite in which pores are
filled with Mg, Mg may increase the pH while it is decomposing, and
thus when the rate of decomposition of the polymer and Mg is
controlled, an additional effect of arbitrarily adjusting the pH in
vivo may be expected.
[0055] According to the present invention, the biodegradable
implant may be used for orthopedics, dental care, plastic surgery
or blood vessels. Specifically, the above implant may be utilized
for an interbody spacer for the spine, a bone filler, a bone plate,
bone pin, bone screw, scaffold, Stent and artificial dental
root.
[0056] II. Method of Manufacturing the Biodegradable Implant
Containing Impurities
[0057] Below is a description of a method of manufacturing the
biodegradable implant according to the present invention.
[0058] According to the present invention, the method of
manufacturing the biodegradable implant comprises a) providing Mg
containing as impurities (i) Mn and (ii) one selected from the
group consisting of Fe, Ni and mixtures of Fe and Ni, wherein the
impurities satisfy the following condition: 0<(ii)/(i).ltoreq.5,
and an amount of the impurities is 1 part by weight or less but
exceeding 0 parts by weight based on 100 parts by weight of the
magnesium; and b) forming the magnesium.
[0059] In a), Mg is preferably provided in the form of being
molten. Specifically, a) is performed by melting Mg in an inert gas
atmosphere such as argon (Ar) that does not react with Mg or in a
vacuum. Also, providing the molten Mg in a) may be carried out
using a variety of processes, including a resistance heating
process for generating heat by applying electricity to a resistor,
an induction heating process that allows current to flow in an
induction coil, or a laser- or focused light-based process. Among
the above melting processes, a resistance heating process is
particularly useful. It is preferred that the molten alloy (i.e. a
melt) be stirred so that the impurities are well mixed when the Mg
melts.
[0060] According to another embodiment of the present invention, in
the case where there is provided a biodegradable implant obtained
by filling the pores of a porous structure with the Mg alloy, a)
may include a-1) preparing a porous structure; and a-2) filling the
pores of the porous structure with the Mg alloy.
[0061] In a-1), the porous structure may comprise one selected from
the group consisting of a metal, a ceramic and a polymer.
[0062] a-1) is described below for the case when the porous
structure is prepared using only a metal.
[0063] Specifically, a metal is prepared in the form of powder or a
wire. The metal powder or wire is prepared into a preform (a Green
preform). As such, the preform may be obtained using a sintering
process or a modified sintering process.
[0064] The production of the preform using a sintering process is
as follows: first, metal powder or wire is placed in a vessel, or
is pressed by an appropriate force of 100 MPa or less so as to have
weak strength, after which the metal having weak strength is
maintained at a temperature of 2/10.about.9/10 of the melting point
of the metal so that the powder or wire respectively coheres thus
obtaining a preform having mechanical strength.
[0065] Also, the production of the preform using a modified
sintering process is as follows: first, metal powder or wire is
placed in a conductive vessel such as graphite vessel, and high
current is then applied to the conductive vessel so that heat is
instantly generated on the contact portion of the metal powder or
wire thus preparing a sintered body, which is then formed into a
preform.
[0066] a-1) is described below for the case of using a metal and a
polymer to prepare the porous structure.
[0067] Specifically, a metal is prepared in the form of powder or a
wire. Subsequently, the metal powder or wire is mixed with a
polymer, and in the course of increasing the temperature, the
polymer decomposes and disappears at low temperature and the metal
powder or wire is sintered at high temperature, thus obtaining a
preform having the appropriate mechanical strength. As such, the
porosity and the strength of the sintered body are determined by
the sintering temperature, the pressure, the ratio of the polymer
and metal in the mixture, etc., and proper conditions may be
selected as necessary. The sintering temperature may vary depending
on the type of material used to prepare the porous structure, and
is typically set to the level of about 1/2.about.9/10 of the
melting point of the porous structure. Although sintering may occur
even in the absence of pressure, sintering may rapidly progress in
proportion to an increase in pressure. However, as the pressure is
higher, there is a need for additional costs including device cost
and mold cost, and thus the appropriate pressure should be
selected.
[0068] In addition to the above method, a-1) is described below for
the case of using a metal and a polymer to prepare the porous
structure.
[0069] Specifically, the surface of a polymer is plated with a
precious metal, such as gold, platinum, and Pd. Subsequently, the
polymer is removed, thus obtaining a metal porous structure having
better biocompatibility.
[0070] a-1) is described below for the case of using an aqueous
salt and a metal to prepare the porous structure.
[0071] Specifically, an aqueous salt and metal powder are mixed and
then formed at high temperature, thus obtaining a preform. The
aqueous salt may include one or more selected from the group
consisting of NaNO.sub.2, KNO.sub.2, NaNO.sub.3, NaCl, CuCl,
KNO.sub.3, KCl, LiCl, KNO.sub.3, PbCl.sub.2, MgCl.sub.2, CaCl.sub.2
and BaCl.sub.3.
[0072] Subsequently, the preform is pressed at a temperature of
2/10.about.9/10 of the melting point of the metal powder. In the
course of pressing, the metal powder coheres via migration of atoms
to form a structure, and the aqueous salt is contained therein,
thus obtaining a composite. When the composite is immersed in
water, only the aqueous salt may dissolve, resulting in a metal
porous structure having pores. Furthermore, a metal porous
structure may be obtained by completely melting a metal material
and then injecting a foaming agent to generate gas.
[0073] a-1) is described below for the case when a polymer and an
electrolyte having metal ions are used to prepare the porous
structure.
[0074] Specifically, the surface of a porous polymer is plated with
a metal using an electrolyte having metal ions. As such, the metal
ions are not particularly limited, but one or more selected from
the group consisting of Ti, Co, Cr and Zr may be used.
Subsequently, the temperature is increased to remove the polymer,
thereby obtaining a metal porous structure.
[0075] a-2) is described below for the case when the porous
structure is prepared using a ceramic.
[0076] Specifically, fine ceramic grains and a binder polymer are
mixed. The resultant mixture is applied on the surface of a
backbone structure made of a foaming agent such as polyurethane
which is removable, and then dried thus preparing a porous
structure. Thereafter, when the temperature is increased, the
polymer is combusted and removed at a temperature near the
combustion temperature of the binder polymer. When the temperature
is further increased, the remaining ceramic grains are mutually
sintered, resulting in a porous structure having mechanical
strength.
[0077] As such, the fine ceramic grains may comprise one or more
selected from the group consisting of hydroxyapatite (HA), zirconia
and alumina.
[0078] a-1) may be a modification or combination of the above
methods of producing the porous structure, or may be a method of
forming a porous structure having different porosities inside and
outside by applying it to some of heterogeneous materials. The
latter method enables the production of a porous structure the
density of the inside of which is high because there are few or no
pores and the porosity of the outside of which is high so that the
porosity is different at different positions. This method may be
employed upon production of an implant that may endure high
external stress throughout its entirety while inducing a high rate
of bone formation on the surface of the implant Furthermore, the
production of the porous structure as above is only an illustration
among a variety of methods of producing a porous structure, and the
scope of the present invention is not limited by variations of the
methods of producing the porous structure.
[0079] a-2) may include one selected from the group consisting of
immersing the porous structure in a molten Mg solution, allowing a
molten Mg solution to flow in the fixed porous structure so that
pores are filled therewith, and applying an external pressure of 1
atm or more in the above two cases so that molten Mg is more easily
charged in the pores of the porous structure. As such, in order to
prevent the molten Mg from solidifying in the course of the pores
being filled therewith, the porous structure may be heated or a
variety of surface contaminants may be removed so that the molten
Mg is easily charged in the pores.
[0080] Also, a-2) may be as follows: Mg is vaporized at high
temperature, preferably 700.degree. C. or more, so that Mg vapor is
deposited on the surface of the pores while passing through the
pores of the porous structure, thus filling the pores of the porous
structure with Mg.
[0081] Also, a-2) may be as follows: an Mg-containing salt is
melted in a liquid, after which Mg is adsorbed on the surface of
the pores of a porous structure while passing the porous structure
through the liquid.
[0082] As another modification in addition to the above filling
processes, only part of pores of the porous structure may be filled
with the Mg alloy, instead of all of them being filled therewith.
Specifically, the molten Mg is charged in the porous structure,
after which high-pressure gas is blown into the porous structure or
the porous structure is rotated or stirred before Mg is completely
solidified. Thereby, non-solidified Mg is removed from the porous
structure and only part of Mg may be left behind in the pores, thus
obtaining a composite in which part of the pores is impregnated
with Mg. In this case, a rate of charging Mg may be differently
controlled at positions of the pores of the porous structure.
[0083] As another modification, the application of Mg is controlled
such that Mg is applied only to the surface of the backbone of the
porous structure and a predetermined portion of the pores may
remain unfilled, and thereby additional effects are expected
including it being easier to form bone by Mg while maintaining
spaces wherein the fine blood vessels necessary to form bone may be
easily formed in the implant.
[0084] In the case of a polymer having a melting point lower than
that of Mg, when a porous structure is first prepared and then
pores thereof are filled with molten Mg, the polymer porous
structure cannot maintain its shape. Thus, the biodegradable
polymer having a polymer and Mg may be manufactured by mixing Mg
powder and the polymer at a volume ratio of 5:95 to 95:5,
increasing the temperature to 150.about.500.degree. C. and applying
pressure in the range of 1 atm to 100 atm. The above conditions are
preferable for the manufacture of the polymer-Mg biodegradable
implant, but under conditions falling outside of the above
conditions, the polymer-Mg biodegradable implant may also be
formed. Thus it will infringe the scope of the present invention to
change the manufacturing conditions for manufacturing the
polymer-Mg biodegradable implant.
[0085] The method of manufacturing the porous structure made of
metal, ceramic and polymer, the method of filling pores of the
porous structure with Mg alloy, and the method of manufacturing the
Mg-filled polymer biodegradable implant are merely illustrative in
the present invention, and the scope of the present invention is
not limited thereto.
[0086] In the method of manufacturing the biodegradable implant
according to the present invention, b) may be forming the molten Mg
alloy for controlling a biodegradation rate using one or more
selected from the group consisting of cooling, extrusion and metal
processing.
[0087] The cooling process may be used to enhance the mechanical
strength of the Mg alloy. Specifically, when Mg is melted in a),
immersing a crucible including molten Mg in water may be utilized.
Also, the molten Mg may be cooled by spraying an inert gas such as
argon. The cooling process using spraying is performed at a much
higher r ate thus obtaining a very fine framework. However, in the
case where Mg is cast in a small size, it should be noted that a
plurality of pores (black portion) be formed therein.
[0088] The extrusion process is used to make the framework of the
Mg uniform and enhance mechanical performance. The extrusion
process may be performed at 300.about.450.degree. C. Furthermore,
the extrusion of Mg may be carried out in a ratio of reduction in
the cross-sectional area before and after extrusion (an extrusion
ratio) of 10:1.about.30:1. As the extrusion ratio becomes higher,
the fine framework of the extrusion material may become uniform,
and defects caused upon casting may be easily removed. In this
case, it is preferred that the capacity of an extrusion device be
increased.
[0089] The metal processing is not particularly limited so long as
it is known in the art. For example, molten Mg may be poured onto a
mold processed to have a shape close to a shape of a final product
and thus directly cast, or may be prepared into an intermediate
material such as a rod or a sheet and then subjected to turning or
milling, and also the Mg alloy may be forged at a higher pressure
thus obtaining a final product.
[0090] III. Biodegradable Implant Represented by Mg--Ca--X
[0091] The biodegradable implant according to the present invention
comprises an Mg alloy which is represented by Chemical Formula 1
below and comprises based on the total weight thereof, 23 wt % or
less but exceeding 0 wt % of Ca, 10 wt % or less but exceeding 0 wt
% of X, and a remainder of Mg.
Mg--Ca--S <Chemical Formula 1>
[0092] In Chemical Formula 1, X is Mn or Zn.
[0093] When the Mg alloy falls within the above range, a
biodegradable implant in which mechanical properties and corrosion
resistance are simultaneously improved and brittleness fractures do
not occur may be provided.
[0094] Also, the Mg alloy preferably comprises, based on the total
weight thereof, 23 wt % or less but exceeding 0 wt % of Ca,
0.1.about.5 wt % of X and the remainder of Mg, and more preferably
23 wt % or less but exceeding 0 wt % of Ca, 0.1.about.3 wt % of X
and the remainder of Mg. When the same corrosion rate is embodied,
the case where the amount of impurities is low is favorable for
fear of the impurities causing side effects.
[0095] According to the present invention there may be provided a
biodegradable implant obtained by filling pores of a porous
structure with the Mg alloy represented by Chemical Formula 1,
comprising, based on the total weight thereof, less than 23 wt %
but exceeding 0 wt % of Ca, less than 10 wt % but exceeding 0 wt %
of X, and a remainder of Mg.
[0096] The size of pores of the porous structure is preferably
200.about.500 Elm. The pore size may be adjusted depending on the
application field using typical methods of the art When the pore
size falls within the above range, it is easy to allow blood
vessels responsible for supplying nutrients, minerals and ions to
pass through the pores.
[0097] The porous structure may have a porosity of 5.about.95%. The
porosity is a volume ratio of pores relative to total volume. In
the case where the required strength of a target is high, the
porosity is decreased so that the strength of the porous structure
may be increased. For example, the case where the porous structure
is a metal such as tantalum having high strength or merely
functions to fill the cavities of lost bone, high porosity thereof
does not cause problems.
[0098] The porous structure may be formed of one or more selected
from the group consisting of a metal, a ceramic and a polymer. The
metal may include one or more selected from the group consisting of
titanium or a titanium alloy, a cobalt-chromium alloy and stainless
steel. The ceramic may include one or more selected from the group
consisting of calcium phosphate, alumina, zirconia and magnesia.
The polymer may include one or more selected from the group
consisting of polyethylene, polylactic acids (PLA), polyglycolic
acid (PGA) and a copolymer thereof such as PLGA. In the case where
the porous structure is made with the above polymer, a
biodegradable acid may be produced thus decreasing the pH. As such,
in the case of a polymer composite comprising pores filled with the
Mg alloy, Mg may increase the pH while it is decomposing, and thus
an additional effect of arbitrarily adjusting the pH in vivo via
control of the rate of decomposition of the polymer and Mg may be
expected.
[0099] The biodegradable implant according to the present invention
may be used for orthopedics, dental care, plastic surgery or blood
vessels. Specifically, the above implant may be utilized for an
interbody spacer for the spine, a bone filler, a bone plate, bone
pin, bone screw, scaffold, and artificial dental root
[0100] IV. Method of Manufacturing the Biodegradable Implant
represented by Mg--Ca--X
[0101] Below is a description of a method of manufacturing the
biodegradable implant according to the present invention.
[0102] The biodegradable implant according to the present invention
is manufactured by i) providing an Mg alloy represented by Chemical
Formula 1 below, comprising based on the total weight thereof less
than 23 wt % but exceeding 0 wt % of Ca, less than 10 wt % but
exceeding 0 wt % of X, and less than 100 wt % but exceeding 67 wt %
of Mg; and ii) forming the Mg alloy.
Mg--Ca--X <Chemical Formula 1>
[0103] In Chemical Formula 1, X is Mn or Zn.
[0104] The description of the Mg alloy is as above and is omitted
herein.
[0105] i) is preferably providing the Mg alloy in a molten state.
The description of i) is the same as that of a) and is thus
omitted.
[0106] According to another embodiment of the present invention, in
the case where there is provided a biodegradable implant resulting
from filling the pores of a porous structure with the above Mg
alloy, i) may comprise i-1) preparing a porous structure and i-2)
filling the pores of the porous structure with the Mg alloy.
[0107] The description of i-1) and i-2) is the same as that of a-1)
and a-2) and is thus omitted.
[0108] In the method of manufacturing the biodegradable implant
according to the present invention, may be forming the molten Mg
alloy for controlling a biodegradation rate using one or more
selected from the group consisting of cooling, extrusion and metal
processing.
[0109] The description of ii) is the same as that of b) and is thus
omitted.
[0110] V. Method of Manufacturing Biodegradable Implant Using
Ultrasound
[0111] The present invention provides a method of manufacturing a
biodegradable implant, comprising applying ultrasound to the
biodegradable implant comprising Mg. When ultrasound is applied to
the biodegradable implant comprising Mg, the corrosion rate may
increase in vivo, so that the implant may disappear within a
shorter period of time.
[0112] The biodegradable implant comprising Mg may be a porous
structure, wherein Mg contains as impurities (i) Mn and (ii) one
selected from the group consisting of Fe, Ni and mixtures of Fe and
Ni, wherein the impurities satisfy the following condition:
0</(i).ltoreq.5, and an amount of the impurities is 1 part by
weight or less but exceeding 0 parts by weight based on 100 parts
by weight of the magnesium. Also, the biodegradable implant may
include an Mg alloy represented by Chemical Formula 1 below,
comprising based on the total weight thereof, less than 23 wt % but
exceeding 0 wt % of Ca, less than 10 wt % but exceeding 0 wt % of
X, and less than 100 wt % but exceeding 67 wt % of Mg.
Mg--Ca--X <Chemical Formula 1>
[0113] In Chemical Formula 1, X is Mn or Zn.
[0114] The biodegradable implant according to the present invention
may be advantageously present in vivo for a long period of time
because the biodegradation rate is controlled to be very low. Also,
in the case where the biodegradable implant according to the
present invention includes a porous structure, blood vessels that
pass through the pores are formed, thus increasing the rate at
which bone is formed and decreasing Young's modulus to thereby
reduce stress shielding. Also, the biodegradable implant according
to the present invention may have enhanced mechanical strength and
impact resistance. Also, the biodegradable implant according to the
present invention may be simultaneously improved in terms of
corrosion resistance and mechanical properties. Thus, the implant
according to the present invention is adapted to be used in bone
replacements or treatment for bone and may be used for orthopedics,
dental care, plastic surgery or blood vessels.
[0115] VI. Biodegradable Implant Having Controlled Mn Content
[0116] The biodegradable implant according to the present invention
comprises, based on the total weight thereof, 10 wt % or less but
exceeding 0 wt % of Mn; 1 wt % or less but exceeding 0 wt % of Fe;
and 99 wt % to less than 100 wt % of a metal comprising Mg. As
such, the Mn content may be set to 0.3.about.0.6 wt %.
[0117] In the biodegradable implant according to the present
invention, Fe is further included as an impurity.
[0118] The biodegradable implant according to the present invention
includes Mn in the above content range, which is bound with Fe
contained in the metal comprising Mg thus decreasing a difference
in potential to thereby reduce galvanic corrosion. Furthermore, Fe
contained in the metal comprising Mg is enclosed with Mn so that
contact between Mg and Fe is blocked, thus preventing or reducing
the corrosion.
[0119] Here, the metal comprising Mg may be pure Mg, Mg having a
very small amount of impurity, or an Mg alloy. This impurity X may
be selected from the group consisting of zirconium (Zr), molybdenum
(Mo), niobium (Nb), tantalum (Ta), titanium (Ti), strontium (Sr),
chromium (Cr), manganese (Mn), zinc (Zn), silicon (Si), phosphorus
(P) and nickel (Ni).
[0120] VII. Biodegradable Implant Comprising Magnesium Oxide
[0121] The biodegradable implant according to the present invention
comprises, based on the total weight thereof, 90 wt % or less but
exceeding 0 wt % of magnesium oxide (MgO); and 10 wt % to less than
100 wt % of a metal comprising Mg.
[0122] When MgO is contained in the above amount in the
biodegradable implant according to the present invention, the
corrosion properties of the biodegradable implant are controlled,
thus preventing swelling due to hydrogen being generated upon
insertion of the biodegradable implant in vivo.
[0123] As the amount of MgO is higher in the biodegradable implant
according to the present invention, the corrosion of the metal
comprising Mg may be reduced. However, it is very preferred that
MgO be contained in the above amount range.
[0124] The metal comprising Mg may be pure Mg, Mg having a very
small amount of impurity, or an Mg alloy. This impurity X may be
selected from the group consisting of zirconium (Zr), molybdenum
(Mo), niobium (Nb), tantalum (Ta), titanium (Ti), strontium (Sr),
chromium (Cr), manganese (Mn), zinc (Zn), silicon (Si), phosphorus
(P) and nickel (Ni).
[0125] VIII. Biodegradable Implant Having Controlled Corrosion
Properties via Extrusion
[0126] The biodegradable implant according to the present invention
may prevent PCP (Preferred Crystallographic Pitting Corrosion)
caused by coarse crystal grains therein, using extrusion.
Specifically, when crystal grains are coarse, the probability of
corrosion between the crystal grains is high. The size of crystal
grains is decreased via extrusion so that the intervals between
crystal grains are decreased, thereby preventing such
corrosion.
[0127] As such, the ratio of reduction in the cross-sectional area
before and after extrusion (the extrusion ratio) is not
particularly limited so long as it is 2:1 or more, but preferably
exceeds 25:1 or 20:1.
Mode for Invention
[0128] The following examples which are set forth to illustrate but
are not to be construed as limiting the present invention, may
provide a better understanding of the present invention which is
about the manufacturing of biodegradable implants comprising Mg or
an Mg alloy for controlling the biodegradation rate.
EXAMPLES 1, 2 AND COMPARATIVE EXAMPLE 1
Manufacturing of Biodegradable Implant Comprising Mg Alloy for
Controlling Biodegradation Rate Comprising 1 Part by Weight or Less
but Exceeding 0 Parts by Weight of Total of Impurities Including
Mn, Fe and Ni based on 100 parts by weight of Mg and the Impurities
Satisfying the Following Condition: 0<{Fe+Ni}/Mn.ltoreq.5
[0129] Fe, Ni, Al, Mn and Mg in the amounts shown in Table 1 below
were charged in a crucible having an inner diameter of 50 mm made
of stainless steel (SUS 410). Subsequently, while Ar gas was
allowed to flow around the crucible so that Fe, Ni, Mn, Al and Mg
in the crucible did not come into contact with air, the temperature
of the crucible was increased to about 700.about.750.degree. C.
inside a resistance heating furnace so that the Fe, Ni, Al, Mn and
Mg melted. The crucible was stirred so that the molten Fe, Ni, Al,
Mn and Mg were well mixed. The completely molten Mg alloy was
cooled, thus preparing an Mg alloy in the solid phase. Also upon
cooling, the crucible was immersed in water to enhance the
mechanical strength of Mg, whereby the molten Mg alloy was rapidly
cooled.
[0130] The Mg alloy in the solid phase was extruded at 400.degree.
C. under conditions of the ratio of reduction in the
cross-sectional area before and after extrusion (the extrusion
ratio) being setto 15:1.
TABLE-US-00001 TABLE 1 Ni Al Mn Fe (wt (wt (wt Mg (Fe + Ni)/ (wt
part) part) part) part) (wt part) Mn Ex. 1 0.0014 0.0002 0.0021
0.0015 100 2.26 Ex. 2 0.0092 0.0027 0.0043 0.0380 100 0.313 C. Ex.
1 0.0214 0.0027 0.0053 0.0036 100 6.69
Test Example 1
Evaluation of Corrosion Rate of Biodegradable Implant Comprising Mg
Alloy
[0131] The biodegradable implants of Examples 1 and 2 and
Comparative Example 1 were immersed in a solution having a
composition of Table 2 below, and thus the corrosion rate was
evaluated based on the hydrogen evolution amount in relation to the
immersion time. The results are shown in FIG. 1.
TABLE-US-00002 TABLE 2 Molar Concentration [mM/L] Mass [g]
CaCl.sub.2 2H.sub.2O 1.26 0.185 KCl 5.37 0.400 KH.sub.2PO.sub.4
0.44 0.060 MgSO.sub.4.cndot.7H.sub.2O 0.81 0.200 NaCl 136.89 8.000
Na.sub.2HPO.sub.4 2H.sub.2O 0.34 0.060 NaHCO.sub.3 4.17 0.350
D-Glucose 5.55 1.000
[0132] With reference to FIG. 1, in Example 1, hydrogen began to
occur after 50 hours, and in Example 2, hydrogen was not almost
generated from initial immersion to after 200 hours, and thus the
implant was slightly corroded. However, in Comparative Example 1,
hydrogen was generated from initial immersion. Hence, the
biodegradation rate of the biodegradable implants of Examples 1 and
2 satisfying the following condition: 0<{Fe+Ni}/Mn.ltoreq.5 was
slower than that of Comparative Example 1 satisfying the following
condition: {Fe+Ni}/Mn>5
EXAMPLES 3 TO 11 AND COMPARATIVE EXAMPLES 2 TO 5
Manufacturing of Biodegradable Implant
[0133] Mg, Ca, Mn and Zn in the amounts shown in Table 3 below were
charged in a crucible having an inner diameter of 50 mm made of
stainless steel (SUS 410). Subsequently, while Ar gas was allowed
to flow around the crucible so that Mg, Ca, Mn and Zn in the
crucible did not come into contact with air, the temperature of the
crucible was increased to about 700.about.750.degree. C. inside a
resistance heating furnace so that the Mg, Ca, and Mn melted. The
crucible was stirred so that the molten Mg, Ca, and Mn were well
mixed. The completely molten Mg alloy was cooled, thus preparing an
Mg alloy in the solid phase. Also upon cooling, the crucible was
immersed in water to enhance the mechanical strength of Mg, whereby
the molten Mg alloy was rapidly cooled.
[0134] The Mg alloy in the solid phase was extruded at 400.degree.
C. under conditions of the ratio of reduction in the
cross-sectional area before and after extrusion (the extrusion
ratio) being set to 15:1.
TABLE-US-00003 TABLE 3 Mg (wt %) Ca (wt %) Mn (wt %) Zn (wt %) Ex.
3 89 10 1 -- Ex. 4 88.98 9.99 -- 1.03 Ex. 5 86.29 10.8 -- 2.91 Ex.
6 84.42 10.7 -- 4.88 Ex. 7 94.88 4.62 -- 0.50 Ex. 8 94.52 4.72 --
0.76 Ex. 9 93.86 4.51 -- 1.63 Ex. 10 92.44 4.56 -- 3.00 Ex. 11
91.23 4.65 -- 4.12 C. Ex. 2 95 5 -- -- C. Ex. 3 89.9 10.1 -- -- C.
Ex. 4 100 C. Ex. 5 AZ91: Al: 8.5~9.5%, Zn: 0.45~9%, Mg: the
remainder Mg: purity 99.98% Mg, MP21-31-31 (available from
TIMMINCO)
Test Example 1
Evaluation of Mechanical Strength of Biodegradable Implant using Mg
Alloy
[0135] FIG. 2 shows results of evaluating mechanical strength of
the biodegradable implant before extrusion, and FIG. 3 shows
results of evaluating mechanical strength of the biodegradable
implant before extrusion.
[0136] With reference to FIGS. 2 and 3, before extrusion, Example 3
had a yield strength of 180 Mpa, which was slightly lower than 220
MPa of Comparative Example 3, and also after extrusion, Example 3
had 280 MPa which was slightly lower than 320 MPa of Comparative
Example 3. However, because 280 MPa is a value that is sufficiently
applicable to implant products that undergo loads, the
corresponding implant may be reasonably applied to products. Also,
the elongation did not reach 7.about.10% before extrusion and was
increased to 12.about.16% after extrusion. This means that
performance in terms of enduring a strong external impact is
superior.
[0137] Example 4 had a strength of 170 Mpa which was lower than 220
MPa, but maintained 320 Mpa equal to that of Comparative Example 3
after extrusion. The elongation was increased from 12% before
extrusion to 17% after extrusion and thus mechanical properties
were equal to or better than those of Comparative Example 3.
[0138] Here, the yield strength refers to the strength at the point
in time at which the gradient changes in each graph.
[0139] Test Example 2: Evaluation of Corrosion Rate of
Biodegradable Implant Using Mg Alloy
[0140] The biodegradable implants of Examples 3 to 11 and
Comparative Examples 3 to 6 were immersed in a biomimetic solution
having a composition of Table 2, and thus the corrosion rate was
evaluated based on the hydrogen evolution rate in relation to the
immersion time. This is because the corrosion rate of an implant is
typically determined from the hydrogen evolution rate in the
biomimetic solution because hydrogen is generated upon the
biodegradation of Mg.
[0141] FIG. 4 is a graph showing the hydrogen evolution rate in
relation to the immersion time in Examples 3 and 4 and Comparative
Example 3. FIG. 5 is a graph showing the hydrogen evolution rate in
relation to the immersion time in Examples 4 to 6 before extrusion.
FIG. 6 is a graph showing the hydrogen evolution amount in relation
to the immersion time in Examples 7 to 11 and Comparative Examples
2 and 4 before extrusion. FIG. 7 is a graph showing the hydrogen
evolution amount in relation to the Zn content.
[0142] With reference to FIG. 4, in Comparative Example 3, rapid
decomposition began to occur after 5 hours, but in Example 3 rapid
decomposition began to occur after 17 hours. In Example 4, 30 days
after immersion, drastic corrosion did not take place. Thus the
biodegradable implants according to the present invention exhibited
superior corrosion resistance compared to Comparative Example
3.
[0143] With reference to FIGS. 5 and 6 showing the corrosion rate
in relation to the Zn content, the corrosion rate was increased in
proportion to an increase in the Zn content.
[0144] With reference to FIG. 7, the corrosion rate in relation to
the Zn content was represented when the hydrogen evolution amount
was 0.5 ml/cm.sup.2. In terms of the corrosion rate, the optimal
composition of the present alloy was 0.118 5% and preferably
0.1.about.3%. The reason is that the corrosion rate zone is the
same, but the low Zn content is regarded as good on the assumption
of the same corrosion rate in light of the side effects that Zn has
on the human body.
[0145] On the axis x, 0.5 designates Example 7, 0.76 designates
Example 8, 1.63 designates Example 9, 3 designates Example 10 and
4.12 designates Example 11.
[0146] FIG. 8 is an electron microscope image showing the surface
of the implant sample of Example 7 immersed in the biomimetic
solution for 61 hours, and FIG. 9 is an EDS image showing the
surface of the implant sample of Example 7. FIG. 10 is an image
showing the implant sample of Example 7 from which the corrosion
material was removed.
[0147] With reference to FIGS. 8 and 9, the corrosion material was
produced on the surface. The components of the corrosion material
are given in Table 4 below.
TABLE-US-00004 TABLE 4 Component Mass (%) Atom (%) O 33.076 52.0767
Mg 5.580 5.7816 P 19.398 15.7781 Ca 41.946 26.3635 Total 100.000
100.0000
[0148] As is apparent from Table 4, oxygen was measured as a
component of the corrosion material, from which the implant sample
of Example 7 was oxidized, and phosphorus and calcium were derived
from the biomimetic solution. Thus due to the corrosion material
including phosphorus and calcium, bone binding effects could be
increased.
[0149] FIG. 10 shows the implant sample from which the corrosion
material shown in FIGS. 8 and 9 was removed. The results of
analyzing the implant sample of Example 7 having no corrosion
material are shown in Table 5 below.
TABLE-US-00005 TABLE 5 Component Mass (%) Atom (%) O 7.749 11.4133
Mg 90.178 87.4252 P 0.521 0.3968 Ca 0.903 0.5305 Zn 0.649 0.2342
Total 100.000 100.0000
[0150] With reference to Table 5, even after the corrosion material
was removed, phosphorus and calcium are left behind. Like this,
phosphorus and calcium derived from the biomimetic solution were
not easily removed.
[0151] FIG. 11 is an image showing the cross-section of the implant
sample of Example 7 immersed in the biomimetic solution for 61
hours, FIG. 12 is an enlarged image of the image of FIG. 11, and
FIG. 13 is of WDS (AA-8500F, available from JEOL) images showing
the implant sample of Example 7 immersed in the biomimetic solution
of Table 2 for 61 hours.
[0152] With reference to FIGS. 11 to 13, the bright line region in
Mg designates Mg.sub.2Ca, and the dark line region designates a
corroded portion. The corrosion was observed to progress while the
black line gradually penetrated in Mg.
[0153] FIG. 14 is an image showing the cross-section of the implant
sample of Example 8 immersed in the biomimetic solution for 61
hours.
[0154] FIG. 15 is of WDS (AA-8500F, available from JEOL) images
showing the implant sample of Example 8 immersed in the biomimetic
solution for 61 hours.
[0155] With reference to FIGS. 14 and 15, Mg.sub.2Ca(Zn) was
enclosed with the Mg--Ca--Zn compound. When the Zn content was
increased, Zn was further contained in Mg.sub.2Ca.
Test Example 3
Evaluation of Corrosion Rate of Biodegradable Implant using Mg
Alloy
[0156] The yield strength, fracture strength and the elongation of
the implant samples of Examples 7 to 11 and Comparative Example 2
were measured. The results are shown in Table 6 below.
TABLE-US-00006 TABLE 6 Yield Strength/Fracture Strength Elongation
(%) Ex. 7 84 .+-. 3/180 .+-. 10 11.8 .+-. 0.4 Ex. 8 107 .+-. 2/240
.+-. 15 13.9 .+-. 1.5 Ex. 9 97 .+-. 2/203 .+-. 10 9.5 .+-. 1 Ex. 10
103 .+-. 2/255 .+-. 14 12.2 .+-. 0.6 Ex. 11 109 .+-. 2/247 .+-. 11
14.6 .+-. 2.sup. C. Ex. 2 87 .+-. 3/180 .+-. 10 10.5 .+-. 0.3
Test Example 4
Evaluation of Corrosion Rate Upon Applying Ultrasound to
Biodegradable Implant Using Mg Alloy
[0157] The implant sample of Example 8 was cut to a width of 9.65
cm, a length of 19.66 cm, and a thickness of 1.18 cm, thus
preparing two samples. Ultrasound was applied to two samples, and
then the samples were immersed in the biomimetic solution of Table
2 for 3 hours and the hydrogen evolution amount was measured. The
results are shown in FIGS. 15 and 16.
[0158] With reference to FIGS. 16 and 17, the sample to which
ultrasound was applied generated a large amount of hydrogen, and
thus was more quickly corroded.
EXAMPLES 12 TO 14
Manufacturing of Biodegradable Implant
[0159] Mg and Mn in the amounts shown in Table 7 below were Charged
in a crucible having an inner diameter of 50 mm that was made of
stainless steel (SUS 410). Subsequently, while Ar gas was allowed
to flow around the crucible so that Mg and Mn in the crucible did
not come into contact with air, the temperature of the crucible was
increased to about 700.about.750.degree. C. inside a resistance
heating furnace, so that the Mg and Mn melted. The crucible was
stirred so that the molten Mg and Mn were well mixed. The
completely molten Mg alloy was cooled, thus preparing an Mg alloy
in the solid phase. Also upon o cooling, the crucible was immersed
in water to enhance the mechanical strength of Mg, whereby the
molten Mg alloy was rapidly cooled, resulting in a biodegradable
implant.
TABLE-US-00007 TABLE 7 Mg (wt %) Mn (wt %) Ex. 12 Remainder 0.0015
Ex. 13 Remainder 0.097 Ex. 14 Remainder 0.51 Mg: purity 99.98% Mg,
MP21-31-31 (available from TIMMINCO)
Test Example 5
Evaluation of Corrosion Rate of Biodegradable Implant in Relation
to Controlled Mn Content
[0160] The implant samples of Examples 12 to 14 were cut to a width
of 9.65 cm, a length of 19.66 cm, and a thickness of 1.18 cm, thus
preparing two samples. Ultrasound was applied to the two samples,
after which the samples were immersed in the biomimetic solution of
Table 2 for 3 hours, and the hydrogen evolution amount was
measured. The results are shown in FIG. 18.
[0161] With reference to FIG. 18, when Mn was added in an amount of
1 wt % or less but exceeding 0 wt %, corrosion began to occur after
50 hours. Corrosion properties were the most efficiently controlled
when Mn was added in an amount of 0.5 wt % or more.
Test Example 6
Evaluation of Corrosion Rate of Extruded Biodegradable Implant
[0162] The biodegradable implant of Example 14 was extruded at
400.degree. C., and the ratio of reduction in the cross-sectional
area before and after extrusion (the extrusion ratio) was set to
25:1.
[0163] The biodegradable implant of Example 14 before and after
extrusion was immersed in the biomimetic solution of Table 2 for 3
hours and the hydrogen evolution amount was measured.
[0164] FIG. 19 is of images showing the crystal grains when the
biodegradable implant of Example 14 was not extruded.
[0165] With reference to FIG. 19, PCP occurred along the crystal
grains.
[0166] FIG. 20 is a graph showing corrosion properties of the
biodegradable implant of Example 14 before and after extrusion.
[0167] With reference to FIG. 20, when extrusion was not performed,
corrosion properties were deteriorated.
EXAMPLE 15
Manufacturing of Biodegradable Implant
[0168] Mg and MgO in the amounts shown in Table 8 below were
charged in a crucible having an inner diameter of 50 mm made of
stainless steel (SUS 410). Subsequently, while Ar gas was allowed
to flow around the crucible so that Mg and MgO in the crucible did
not come into contact with air, the temperature of the crucible was
increased to about 700.about.750.degree. C. inside a resistance
heating furnace, so that the Mg and MgO melted. The crucible was
stirred so that the molten Mg and MgO were well mixed. The
completely molten Mg alloy was cooled, thus preparing an Mg alloy
in the solid phase. Also upon cooling, the crucible was immersed in
water to enhance the mechanical strength of Mg, whereby the molten
Mg alloy was rapidly cooled, resulting in a biodegradable
implant.
TABLE-US-00008 TABLE 8 Mg (wt %) MgO (wt %) Ex. 15 Remainder 10 Mg:
purity 99.98% Mg, MP21-31-31 (available from TIMMINCO)
Test Example 7
Evaluation of Hydrogen Evolution Amount of Biodegradable Implant
Comprising MgO In Vivo
[0169] The biodegradable implant samples of Example 15 and
Comparative Example 4 were inserted into a rat to evaluate the
hydrogen evolution amount in vivo.
[0170] FIG. 21 is a photograph showing the rat having the
biodegradable implant sample of Comparative Example 4 inserted
therein.
[0171] With reference to FIG. 21, hydrogen was generated in the
rat, thus causing swelling.
[0172] However, when the biodegradable implant sample of Example 15
was inserted into the rat, there was no swelling.
* * * * *