Field of the Invention:-
The present invention relates to an implantable device having antimicrobial
coating and a method of manufacturing the same.
In particularly, the present invention relates to an implantable device having
antimicrobial coating having nanotechnological bonding and a method of
manufacturing thereof.
Background of the Invention:-
The polyethylene is used in certain medical devices like the Intra Uterine
Devices (IUDs) due to its excellent mechanical properties and relatively high
biocompatibility. The IUDs are generally classified as copper releasing IUDs
and hormone releasing IUDs. The copper releasing IUDs are generally made
2
of low density polyethylene [LDPE] generally with 220-380mm exposed area
of copper on its arms and stem.
The copper releasing IUDs, inspite of being the second most popular form of
contraception in India today, are unable to prevent Sexually Transmitted
diseases [STDs] and Pelvic Inflammatory diseases [PIDs] which seriously
restrict their usage.
Therefore, the copper releasing IUDs are coated with an antimicrobial
component. However, major drawback of copper releasing IUDs made from
LDPE is that polyethylene show poor adhesive properties to a coating since it
is characterized by low surface energy values, chemical inertness and
smooth surface. For this reason LDPE films need, in many cases, some
additional treatment to raise surface activity, thus enhancing wettability
and, consequently, the adhesive properties.
The US Patent no. 5,984,905 [US'905] describes a process of forming an
antimicrobial coating over a medical implant. In accordance with this prior
art the coating comprising an effective amount of antimicrobial metal atoms
is incorporated in a coating of amorphous carbonaceous material.
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The major limitation of this prior art [US'905] is that it is restricted to metal
atoms of antimicrobial material, which is difficult to be performed.
Another limitation of this prior art [US'905] is that in the process
vaporization of antimicrobial material is needed which alters the properties
of material.
The US Patent no. 7,250,195 [US'195] describes a molecular plasma
discharge deposition method for depositing colloidal suspensions of
biomaterials onto metal or non metal surfaces without the loss of biological
activity/structure. The method is based on generating charged corona
plasma introduced in a vacuum chamber for deposition of biomaterial over a
substrate.
The major drawback of this prior art [US'195] is that the effect of corona is
not always beneficial which has been found to result in arcing.
The US Patent no. 7,264,822 [US'822] describes a system for vascular
conditions, including a catheter, a stent coupled with catheter and a
polymeric coating on the stent comprising at least one conjugated drug.
Each conjugated drug comprises of a bioactive agent and a control agent.
The major limitation of this prior art [US'822] is that it results in formation
of a thin coating, which in-turn results in poor adherence, and hence, very
fast diffusion of coated material, and therefore, has been found to be
ineffective for coating a copper releasing IUDs.
The US Patent 7,282,213 [US'213] describes a method for coating a medical
device requiring application of thermal energy onto crystalline drug
deposited on the surface of a medical device to increase molecular mobility
and form a conformable drug coating with a low density of micro-cracks.
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The major limitation of this prior art [US'213] is that during the process,
overheating has been found to result in degradation of antimicrobial
material.
An attempt has been made by coating a copper releasing IUD with a
contraceptive manufactured under the trademark RISUG® [Reversible
Inhibition of Sperm under Guidance] which is a reversible, and potent
spermicidal and antimicrobial contraceptive and currently undergoing
advanced clinical trials in India, by employing Vacuum Plasma [Plasma
surface modification of Low-Density Polyethylene for functionalization in
medical devices (IUDs), Presented by one of the inventors during International
Symposium on Plasma Chemistry (ISPC-18), Kyoto, Japan, Aug. 27, 2007]. In
accordance with this prior art, antimicrobail material is first smeared over
the copper releasing IUD, and the coated IUD is then directly subjected to
Radio Frequency Plasma treatment.
The major limitation of this prior art [ISPC-18] is that it has been found to
result in formation of a thin film, which in-turn results in poor adherence,
and hence, very fast diffusion of coated material.
Further, drawback of this prior art [ISPC-18] is that it results in poor
adhesion of antimicrobial material with material of IUD.
Another drawback of this prior art [ISPC-18] is that during the process
temperature of the IUD and the material being coated increase even more
than 100°C, which in-turn has been found to result in degradation of the
coated material.
Still another drawback of this prior art [ISPC-18] is that it results in
breakdown of the material being coated, meaning thereby there is probability
of chemistry of the material being coated getting changed.
Therefore, it has been found that even this prior art [ISPC-18] is ineffective
for coating a copper releasing IUDs with antimicrobial material.
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Accordingly, it is clear from the foregoing description that none of the above
described prior arts is suitable for coating an implantable device with a
coating material, preferably a copper releasing IUDs with antimicrobial
material.
Need of the Invention:-
Accordingly, there is a need to have an implantable device having a coating,
preferably an implantable device having an antimicrobial coating and a
method of manufacturing thereof which can overcome some of the
limitations and drawbacks of the prior art as described herein.
Objects of the Invention:-
Therefore, main object of the present invention is to provide an implantable
device having a coating, preferably an antimicrobial coating and a method of
manufacturing thereof which can overcome some of the limitations and
drawbacks of the prior art as described herein, and hence, is also effective
for coating a copper releasing IUDs with antimicrobial material.
This is also an object of the present invention to provide an implantable
device having antimicrobial coating which is not restricted to metal atoms of
antimicrobial material, and hence is easier to be performed.
This is also an object of the present invention to provide a method of
manufacturing an implantable device having antimicrobial coating wherein
no vaporization of antimicrobial material is needed, and hence, no alteration
of properties of coated material takes place.
This is also an object of the present invention to provide a method of
manufacturing an implantable device having antimicrobial coating wherein
no arcing takes place.
This is also an object of the present invention to provide a method of
manufacturing an implantable device having antimicrobial coating wherein a
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thick coating can also be formed to have enhanced adherence, and hence,
very slow or no loss of coated material, and therefore, being effective for
coating a copper releasing IUDs.
This is also an object of the present invention to provide an implantable
device having antimicrobial coating wherein the coated material is strongly
adhered with material of IUD.
This is also an object of the present invention to provide a method of
manufacturing an implantable device having antimicrobial coating wherein
no overheating takes place, and hence, no degradation of antimicrobial
material takes place during or after the coating process.
This is also an object of the present invention to provide a method of
manufacturing an implantable device having antimicrobial coating wherein
during the process temperature of the IUD and the material being coated
does not increase more than 40°C, and hence, no degradation of the coated
material takes place.
This is also an object of the present invention to provide a method of
manufacturing an implantable device having antimicrobial coating which
does not result in breakdown of the material being coated, meaning thereby
does not result in change in chemistry of the material being coated.
Other objects and advantages of the present invention will be more apparent
from the following description.
Nature of the invention:-
Accordingly, in one embodiment, the present invention relates to an
implantable device having antimicrobial coating comprising an implantable
device as the substrate and an antimicrobial material as the coating thereon,
wherein the coating has enhanced physical cross-linking at the interface of
the substrate and the coating, and is applied by employing vacuum plasma
treatment under controlled low-pressure conditions.
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Accordingly, in second embodiment, the present invention relates to a
method of manufacturing an implantable device having antimicrobial coating
comprising following steps:-
a) subjecting the surface of the implantable device to the plasma
exposure under controlled conditions;
b) coating the surface of implantable device with antimicrobial material
after treatment of step - a);
c) subjecting the coated surface of the implantable device again to the
plasma exposure under controlled conditions to result in manufacture
of implantable device having antimicrobial coating,
wherein the implantable device is the substrate and antimicrobial material is
the coating thereon having enhanced physical cross-linking at the interface
of the substrate and the coating.
In accordance with present invention, the implantable device can be any
implantable device and the coating can be any coating which are capable of
withstanding the plasma exposure. In accordance with the present invention
the coating is not restricted to metal atoms of antimicrobial material, and
hence it is easier to be performed.
In accordance with one of the preferred embodiments of the present
invention, the implantable device is made of a polymer material, preferably of
polyethylene, polyurethane, polypropylene or alike polymer.
In accordance with one of the preferred embodiments of this invention, the
implantable device is an interuterine device (IUD), preferably a copper
releasing IUD made of low-density polyethylene and comprising a copper
wire.
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In accordance with present invention, the plasma selected is inert argon
plasma, preferably a radio frequency argon plasma.
In accordance with one of the preferred embodiments of this invention, the
surface engineering of the implantable device is achieved by exposure to
radio frequency argon plasma under controlled conditions.
It has been found that exposure to radio frequency argon plasma under
controlled conditions has advantage of causing bombardment on the surface
of the implantable device. In accordance with this invention even the argon
ions, atoms, radicals and electrons under controlled conditions cause
bombardment on the surface of the implantable device resulting in
degassing and cleaning of the surface, and creating micro-pits on its top
layer and activating the surface of the implantable device which in-turn has
been found to have advantage of resulting in enhanced physical cross-
linking of the coating material with the surface of the substrate, and hence
the coated material is strongly adhered with material of substrate.
In accordance with the present invention, it is the implantable device having
its surface having been bombarded with the radio frequency argon plasma
under controlled conditions and having been degassed and cleaned of the
contaminants, and having the micro-pits on its top layer and activated
surface which as described herein has been found to have advantage of
resulting in enhanced physical cross-linking of the coating material with the
surface of the substrate.
In accordance with the present invention, the surface of the implantable
device prepared in preceding step - a) is coated with antimicrobial material.
In accordance with the present invention, the coating of the surface of the
implantable device can be performed by any method known in the art. In one
preferred embodiment, the coating is done by spray coating which has been
found have advantage of providing smooth and uniform coating of the
antimicrobial material.
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In accordance with the present invention, the coated surface of the
implantable device prepared in preceding step - a) and step - b) is subjected
again to the plasma exposure under controlled conditions to result in
manufacture of implantable device having antimicrobial coating, wherein the
coating has been found to have enhanced physical cross-linking at the
interface of the substrate and the coating, which has been found to be
achieved due to degassing and cleaning of the contaminants, and formation
of the micro-pits on top layer and activation of surface of the implantable
device during the bombardment of the surface of the implantable device with
the radio frequency argon plasma under controlled conditions during the
first step - a) of the presently disclosed method.
In accordance with the present invention, the plasma exposure acts as a
micro-hammer to enhance adhesion of the coated antimicrobial molecules
on the micro pitted surface by initiating physical cross-linking at the
interface.
In accordance with the present invention the plasma exposure is carried out
under controlled low-pressure conditions.
It may be noted that present method has advantage of avoiding vaporization
of coating material, i.e. of antimicrobial material, and hence, has advantage
of avoiding alteration of properties of coated material.
Further, during the present method no arcing takes place.
In accordance with the present invention, the coated material may be coated
to any thickness, i.e. from thin coating to thick coating, which has been
found to have enhanced adherence, i.e. strongly adhered with material of
substrate, and hence, having very slow or no loss of coated material, and
therefore, being effective for coating a copper releasing IUDs.
In accordance with present invention, the plasma exposure is carried out
with radio frequency argon plasma under controlled conditions, which are
low-pressure controlled conditions, which has been found to have advantage
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of avoiding overheating, and hence, degradation of antimicrobial material
during or after the coating process.
In accordance with present invention, during the entire process, that is
during step - a) and step - c), the temperature of the surface of the
implantable device and the coating material does not increase more than
40°C, and hence, the present method has been found to have advantage of
avoiding degradation of the coated material.
Further, in accordance with present invention, during the entire process,
that is during step - a) and step - c), no breakdown of the coating material
has been observed, and therefore, no change in chemistry of the coating
material has been observed.
A patterned surface morphology of the coated implanted device prepared in
accordance with present invention by employing the RF argon plasma
treatment under low-pressure controlled conditions reveals the enhanced
physical bonding of the coated material, which for illustration was a
reversible contraceptive manufactured under the trade name RISUG® on the
activated micro-pits formed on the surface of the implantable device, which
for illustration was a copper releasing IUD.
It has been observed that controlled plasma exposure in accordance with
present invention initiates a process similar to micro-hammering in first step
- a) and in third step - c) it initiates a pushing process to push the material
being coated into the micro-pits formed in first step - a) and such close
physical proximity has been found to promote physical cross linking. The
physical cross-linking promoted by the controlled RF argon plasma
treatment of the present invention has been found to enhance the adhesion
of the coated material on the surface of the substratewhich in-turn has been
found to have advantage of resulting in enhanced physical cross-linking of
the coating material with the surface of the substrate, which has been
observed on conducting the peeling force test.
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It has also been observed that the antimicrobial coating material surprisingly
shows enhanced antimicrobial property, which may be attributed to
formation of new charge centers in the coating layer during the third step of
the present invention, that is during the step of subjecting the coated
surface of the implantable device again to the plasma exposure under
controlled conditions.
It has been surprisingly observed that the energy requirement or
temperature increase during the step of bombarding the coated surface of
the implantable device with plasma exposure under controlled conditions
[that is during third step, i.e. during the process step - c) of the present
method] is very low, and hence, it has been observed by IR thermometry and
FTIR and DSC that the low-pressure controlled plasma exposure when
carried out with radio frequency argon plasma in accordance with present
invention does not cause overheating, and hence, does not cause
degradation of antimicrobial material during or after the coating process. It
has also been observed that during the entire process, i.e. during the step -
a) and step - c), the temperature of the surface of the implantable device and
the coating material does not increase more than 40°C, and hence, the
present method has been found to have advantage of avoiding overheating
and degradation of the coated material as well as substrate, and breakdown
of the coating material, and therefore, no change in chemistry of the coating
material was observed.
It is clear from the foregoing description that present invention provides a
new avenue to enhance adhesion of the coating by incorporating the applied
material at the nano-pits by a controlled plasma exposure without changing
the chemistry of the deposited antimicrobial compound as well as not
affecting the chemistry of the coating material and the substrate. A near
ambient condition with inert argon plasma accomplishes such enhancement
of adhesion of the coating material on the surface of the substrate.
It may be noted that present invention has been illustrated by employing a
copper releasing IUD as an implantable device and RISUG® as an
antimicrobial coating, that is as a coating material. However, as described
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herein, the present invention can also be industrialized for coating of any
coating material on any implantabe device which are capable of withstanding
the plasma exposure under controlled conditions.
Dated 27th December 2007.
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Implantable Device having Antimicrobial Coating and a Method of
Manufacturing Thereof.
An implantable device having antimicrobial coating comprising an
implantable device as the substrate and an antimicrobial material as the
coating thereon and a method of manufacturing thereof are provided
wherein the coating has enhanced physical cross-linking at the interface of
the substrate and the coating and is applied by employing vacuum plasma
treatment under controlled low-pressure conditions comprising steps of a)
subjecting the surface of the implantable device to the plasma exposure
under controlled conditions; b) coating the surface of implantable device
with antimicrobial material after treatment of step - a); c) subjecting the
coated surface of the implantable device again to the plasma exposure under
controlled conditions to result in manufacture of implantable device having
antimicrobial coating.