JPH0148777B2 - - Google Patents

Description

BACKGROUND OF THE INVENTION (Technical Field) The present invention relates to medical devices. Specifically, the present invention relates to a medical device having a highly biocompatible hydrophilic surface.

(Prior art) Artificial organs, artificial blood vessels, contact lenses, blood circuits, blood bags, plasma separators, blood tubes,
In medical devices such as tissue or cell culture shears, the surfaces of these devices come into direct contact with living tissue or body fluids, so the original functions of the medical device can be performed without causing any interaction with the living tissues or fluids that these surfaces come into contact with. It is required to be able to perform satisfactorily under conditions of contact with living organisms, that is, to have so-called biocompatibility.

In order to improve the biocompatibility of such medical devices, many studies have been conducted and put into practical use regarding the materials and properties of medical devices, especially the materials and properties of their surfaces. There is. For example, negatively charged surfaces such as anionic polymers or suitably oriented electret polymers, surfaces coated with the natural anticoagulant heparin or synthetic heparin analogs, charged surfaces with an inherently low surface free energy. surface coated with albumin, etc. However, these do not provide fully satisfactory biocompatibility, and the reaction between living organisms and these contact surfaces remains problematic. Recently, since biological membranes are composed of a matrix of phospholipid bilayers, lipids, especially polymerizable lipids, have been used to impart biocompatibility or hydrophilicity to the surfaces of medical devices, especially from the viewpoint of stability. (S.L. Risien, Macromolecules 16 335 (1983) [SL
Regen, Macromol. 16 335 (1983)], Japanese Patent Application Publication No. 1986-
See No. 135, 492. ). As such polymerizable lipids, polyacetylene type lipids having a conjugated diyne as a polymerizable functional group in a hydrophobic acyl chain have been synthesized and numerous studies have been conducted. Regarding the manufacturing method of polyacetylene type lipids, see US Pat. No. 2,816,149, US Pat. No. 2,941,041, and US Pat. Macromol, Chem.,] 180 , 1059
(1979)]. However, in the case of currently developed polyacetylene type lipids,
The conjugated diyne in the molecule is synthesized through numerous reaction steps using pure organic chemistry based on extremely detailed molecular design, and the yield is low, making it difficult to synthesize in large quantities from a practical standpoint. Not only that, but the polystyrene type lipids are very expensive, so medical devices having a polymer coating of these polystyrene type lipids on their surfaces are subject to considerable quantitative and economical constraints. I end up. In addition, this polymerized film of polystyrene-type lipids is formed by polymerization using a chemical initiator or various electromagnetic waves, especially irradiation with ultraviolet rays. If they remain, toxicity problems arise, and with ultraviolet irradiation, for example, when the medical device is a catheter, it has been impossible to form a polymeric film because the ultraviolet rays do not reach the inner surface of the catheter.

OBJECTS OF THE INVENTION It is therefore an object of the present invention to provide a novel medical device. Another object of the present invention is to provide a medical device with high biocompatibility.

A further object of the present invention is to provide a medical device that utilizes a novel polymerizable lipid.

The above objectives are achieved by applying the general formula () as a hydrophobic acyl chain on the surface of at least the part that contacts the living body This is achieved by a medical device characterized by having a hydrophilic surface formed by forming a polymerized film of a polymerizable lipid having at least one acyl chain derived from eleostearic acid represented by:

The present invention also provides that the polymerizable lipid has the general formula () [However, in the formula, R is -(CH ₂ -) ₂ N (CH ₃ ) ₃ , -(
CH ₂ −) ₂ N H ₃ or −CH ₂ −CH(NH ₃ )−
He is the COO. ] This indicates a medical device consisting of a phospholipid represented by the following. The present invention further provides that R in the general formula () is -(CH ₂ -) ₂ N
(CH ₃ ) ₃ indicates a medical device. The present invention further provides a medical device in which the polymer coating is formed by cross-linking and polymerizing a polymerizable lipid by irradiating electromagnetic waves. The present invention also provides a medical device in which the polymer coating is formed by crosslinking and polymerizing a polymerizable lipid by contacting it with oxygen. The present invention further provides a medical device in which the polymeric coating is formed by crosslinking and polymerizing a polymerizable lipid by exposing it to electromagnetic waves and contacting it with oxygen.

DETAILED DESCRIPTION OF THE INVENTION The present invention will now be described in more detail based on embodiments.

The medical device of the present invention is suitable for living organisms, that is,
Includes items that may come into contact with tissues or body fluids, such as artificial organs, artificial blood vessels, contact lenses, blood circuits, blood bags, plasma separators, blood tubes, catheters, and tissue or cell culture vessels. However, it is of course not limited to these. Further, the materials constituting these may be any material such as synthetic resin, natural or synthetic rubber, natural or synthetic fiber, glass, metal, ceramics, etc., and the surface thereof may be either hydrophobic or hydrophilic. Good too.

Therefore, the medical device of the present invention has the general formula () as a hydrophobic acyl chain on the surface of at least the part that contacts the living body It is characterized by having a hydrophilic surface formed by forming a polymerized film of a polymerizable lipid having at least one acyl chain derived from eleostearic acid represented by:

As used herein, "lipid" refers to an amphipathic compound having a hydrophilic polar part and a hydrophobic non-polar part consisting of at least one long-chain aliphatic acyl chain, such as phosphatidylcholine, phosphatidylcholine, Phospholipids such as atidyl etheramine, phosphatidylserine and phosphatidylglycerol, sphingolipids such as sphingomyelin, glycolipids such as ceredoside, plant glycolipids and gangliosides, phosphonoglycerides, etc. phosphonolipids, such as glycerides, glycerol ethers, ceramide-2-aminoethylphosphonic acid and phosphonoglycerides;
In addition, alkyl ammonium halides such as dialkyl phosphates, dialkyl phosphonates, alkyl phosphinate monoalkyl esters, N,N-disubstituted dimethyl ammonium halides, trialkyl methyl ammonium halides, tetraalkylammonium halides, etc. , dialkyl sulfosuccinic acid esters,
Refers to substances having a skeleton of lipids or lipid-like green compounds such as 2,3-diacyloxysuccinic acids. Furthermore, among these, those having a skeleton such as alkylammonium halides have a structure in which an acyl chain is bonded to the end or side of the alkyl chain of the compound serving as the skeleton by an ester bond. . In addition, the names of the lipids and lipid-like green compounds mentioned above are intended to indicate the structure that serves as the backbone of lipids, and therefore should be interpreted in a broad sense including substitutes and similar compounds. Also included are compounds in which the moiety represented by "alkyl" is an unsaturated hydrocarbon group such as alkenyl, alkadienyl, alkatrienyl, and alkynyl.

The polymerizable lipid constituting the polymeric film formed as the hydrophilic surface of the medical device of the present invention is a type of "lipid" as described above, and its hydrophobic acyl chain has an acyl chain of the general formula () synthesized. It was introduced in the From the viewpoint of biocompatibility, the polymerizable lipids include naturally occurring lipid skeletons such as phospholipids, sphingolipids, glycolipids, glycerides, glycerol ethers, and phosphonolipids among the skeletons listed above. It is desirable to have the general formula () [In the formula, R is -(CH ₂ -) ₂ N (CH ₃ ) ₃ (phosphatidylcholine), -(CH ₂ -) ₂ N CH ₃ (kephalin) or -CH ₂ -CH (NH ₃ )-COO (phosphatidylserine), and R ₁ and R ₂ are saturated or unsaturated hydrocarbon groups. ] Typical phospholipids as constituent parts of biological membranes, more preferably those having a phosphatidylcholine skeleton are desired.

Introduction of the hydrophobic acyl group represented by the general formula () into a lipid having the above-mentioned skeleton structure can be easily carried out by a known method using eleostearic acid as a starting material. This eleostearic acid has the general formula (') CH ₃ (CH ₂ ) ₃ CH=CHCH=CHCH=CH (CH ⁺ ) ₇ C
It is a natural unsaturated fatty acid with conjugated double bonds at the 9th, 11th, and 13th positions represented by OOH('), and can be easily extracted from tung oil, accounting for 80 to 95% by weight of mixed fatty acids. The tung oil fatty acid obtained by hydrolyzing this tung oil contains 60% by weight or more, preferably 80% by weight or more of eleostearic acid, and the remaining components include saturated acids, oleic acid, linoleic acid, etc. There is. In order to prepare the polymerizable lipid constituting the polymerized coating of the medical device of the present invention, this tung oil fatty acid may be used as it is as a natural unsaturated fatty acid, and if necessary, column chromatography and/or
Alternatively, only eleostearic acid may be extracted and used after purification by recrystallization or the like.

For example, an acyl chain represented by the general formula () can be introduced from eleostearic acid into the skeleton of a phospholipid as follows. The hydrophilic polar part of the lipid, which is another starting material, is
They can be obtained more easily and in larger quantities than natural phospholipids, many of which have a hydrophobic nonpolar portion of a saturated aliphatic acyl chain. The natural phospholipid is hydrolyzed and subjected to an esterification reaction with eleostearic acid, especially as its metal complex, for example a complex of a metal such as cadmium. In the esterification reaction, a natural phospholipid hydrolyzate or its metal complex is added to a medium such as chloroform, carbon tetrachloride, or methylene chloride and suspended under stirring, and eleostearic acid is added to this suspension. 200 to 400 parts by weight, preferably 300 to 370 parts by weight of an acid anhydride derivative per 100 parts by weight of phospholipid hydrolyzate and an appropriate amount of a catalyst were added, and the inside of the reaction system was replaced with an inert gas such as argon, nitrogen, helium, etc. After that, the reaction is carried out in a dark place at a temperature of 5 to 40°C, preferably 15 to 25°C, for 24 to 90 hours, preferably 40 to 72 hours. Examples of the catalyst include 4-dimethylaminopyridine, and the amount is 50 to 100 parts by weight, preferably 80 parts by weight, per 100 parts by weight of the phospholipid hydrolyzate.
~85 parts by weight are used. After the reaction, white insoluble matter precipitates and is filtered off. The solvent is distilled off under reduced pressure at room temperature, and then redissolved in a mixed solvent of chloroform/methanol/water (volume ratio = 4/5/1) to combine with the ion exchange resin. Contact it and then wash it off. After evaporating the mixed solvent under reduced pressure, it was dissolved in a small amount of chloroform, purified with a chloroform and methanol mixed solvent using a silica gel column, etc., and the general formula () [However, in the formula, R is −(CH ₂ −) ₂ N (CH ₃ ) ₃ , −(
CH ₂ −) ₂ N H ₃ or −CH ₂ −CH(NH ₃ )−
Such as COO. ] An eleostearic acid phospholipid is obtained.

The polymerizable lipid obtained varies depending on the starting material used. For example, when using egg yolk lecithin, eleostearate phosphatidylcholine represented by the general formula (), kephalin, phosphatidylserine, etc. are used. In these cases, polymerizable lipids corresponding to these can be obtained.

The polymerizable lipid obtained in this way has an acyl chain derived from eleostearic acid and has three conjugated double bonds in the chain as represented by the general formula (). When irradiated with electromagnetic waves such as light, ultraviolet rays, β rays, γ rays, and X rays, especially ultraviolet rays, the three conjugated double bonds in this hydrophobic acyl chain easily undergo a crosslinking reaction, causing polymerizable lipids to bond together. Polymerizes and gels to form a stable state. This conjugated triene-type polymerizable lipid has a maximum wavelength of its absorption spectrum at a relatively low-energy position of 270 nm or more (see Figure 2), and because it is polymerized by electromagnetic energy, it cannot be used as a polymerization initiator or sensitizer. , no reducing agent is required,
There is no fear of toxicity due to these additions. Furthermore, it was surprisingly found that a polymerization reaction occurs even when this conjugated triene type polymerizable lipid is simply left in the air. That is, the polymerizable lipid automatically starts an oxidative polymerization reaction in the presence of oxygen, and as a result, forms a stable crosslinked polymer in the same way as when irradiated with electromagnetic waves. Although it is possible that the chemical structure of the polymerized film differs due to such differences in polymerization form, it was clear that all of them exhibited high biocompatibility. Furthermore, the polymerizable lipid is soluble in chloroform, ether, methanol, dimethylformamide, etc. before being exposed to electromagnetic wave irradiation and/or oxygen contact, but when it is polymerized and gelled by irradiation and/or contact, these It is completely insoluble in the solvents, and a significant difference in solubility occurs due to crosslinking polymerization.

The medical device of the present invention has such a polymerized coating of a polymerizable lipid on the surface of at least a portion that comes into contact with a living body, and since the polymerizable lipid is an amphiphilic compound, the surface of the medical device When the property is hydrophobic, the hydrophobic non-polar part of the polymerizable lipid, that is, the acyl chain part, is oriented on the surface and shows good adhesion, and the hydrophilic polar part faces outward, so it can be treated. The surface can be made hydrophilic. Note that since the conjugated triene group, which is a sensitive group that causes crosslinking polymerization, is present in the acyl chain, there is no change in the properties of the hydrophilic polar portion even after crosslinking polymerization and formation of a polymer film. The polymeric film formed on the surface of a medical device is formed by forming a monolayer film of such a polymerizable lipid or by using a Langmuir-Blodgeet method to form a monomolecular layer film of such a polymerizable lipid.
In addition to being provided as a cumulative film by methods such as the Blodgett method (LB method), it is also formed in the form of liposomes. In other words, when the above polymerizable lipids are dispersed in an aqueous solvent by ultrasonication,
It automatically forms endoplasmic reticulum, a so-called liposome, with a bilayer structure of lipids. In the liposome, the hydrophobic groups of the polymerizable lipid are oriented on the inside and the hydrophilic groups are oriented on the outside, and therefore the outer surface properties are also hydrophilic. Since a kind of attractive force acts between these liposomes, a membrane can be formed by the liposome aggregate, and even in such a liposome state, a polymerization reaction occurs due to electromagnetic wave irradiation and/or oxygen contact.

Various methods can be considered for manufacturing the medical device of the present invention, but simply, a solution or liposome suspension of the polymerizable lipid is applied to the surface of at least the parts of the medical device that come into contact with a living body, Coating is performed by evaporating the solvent or dispersion medium. Alternatively, the monomolecular layer of the polymerizable lipid formed on the water surface can be accumulated on the surface of a medical device by the Langmuir-Blodget method. The polymerizable lipid coated on the surface in this manner is cross-linked and polymerized by electromagnetic waves and/or oxygen, and a polymer film of the polymerizable lipid can be supported and fixed on the surface. In particular, polymer coatings that are crosslinked and polymerized by oxygen are difficult to irradiate with electromagnetic waves such as ultraviolet rays on the inner surface that comes into contact with a living body, such as when a medical device is a catheter. It can be formed even if a polymeric film cannot be formed or even if the medical device is made of a material that is likely to be deteriorated by electromagnetic waves.

The medical device of the present invention obtained in this way is
A hydrophilic surface formed by forming a polymerized film of a polymerizable lipid having at least one acyl chain derived from eleostearic acid represented by the general formula () as a hydrophobic acyl chain on the surface of at least the part that comes into contact with a living body. Although the detailed structure of the polymer coating is not clear, it is composed of polymeric lipids with a structure similar to phospholipids, which are constituents of biological membranes, and its surface is hydrophilic. It exhibits high biocompatibility, and since it is in a cross-linked polymerized form, it is stable and does not change even when it comes into contact with living organisms or solvents.

Hereinafter, the present invention will be specifically explained with reference to Examples. In addition, as a reference example, a synthesis example of the polymerizable lipid used will also be described.

Reference Examples Next, the present invention will be explained in more detail with reference to Examples.

Production of eleostearic acid anhydride Tung oil fatty acid equivalent to 80 g of eleostearic acid was dissolved in 600 ml of carbon tetrachloride immediately after dehydration and distillation.
Dicyclohexylcarbodiimide 32.6 to this solution
g was added, the inside of the container was replaced with argon gas, the container was sealed, and the container was left as it was at 25° C. for 24 hours (with occasional stirring). Insoluble components were filtered off and distilled to dryness. When this was purified with silica gel using dichloromethane as a developing solvent, eleostearic anhydride was obtained in a yield of 29%.

Production of egg yolk lecithin (phosphatidylcholine) hydrolyzate cadmium complex Dissolve 45 g of egg yolk lecithin (Kewpie PL-100) in 450 ml of dehydrated ether, filter out insoluble materials,
50 ml of a methanol solution of % strength tetrabutylammonium hydroxide were added and shaken vigorously at a temperature of 25°C. As the reaction progresses, the solution becomes cloudy and the layers gradually separate, so let it stand.
A brown oil was allowed to settle out well and the supernatant was decanted. Dissolve the brown oil with 100ml of dehydrated ether.
After washing twice, the mixture was heated and dissolved in 125 ml of dehydrated methanol, 1 g of a decolorizing agent was added under reflux at the boiling point, and the mixture was filtered while hot. After cooling, 250 ml of dehydrated ether was added to the filtrate, the precipitate was left behind and decanted, and the precipitate was dissolved in 40 ml of hot water. To this was added 8 g of cadmium chloride pentahydrate dissolved in 20 ml of pure water, and further added 2.5 g of activated carbon and 2 g of a decolorizing agent, and after refluxing at the boiling point, the mixture was filtered using a filter paper and a 0.25 μm Millipore filter. Add 100 ethanol to this
When I added 150ml, a colored precipitate was formed, so
When only the cloudy solution from which this was removed was collected, 100 to 150 ml of ethanol was added and vigorously shaken, white crystals were precipitated. After standing overnight at a temperature of 0 to 5°C, the precipitated crystals were collected by filtration, washed with dehydrated methanol, dehydrated ether, and dehydrated benzene in this order, and further vacuum-dried over phosphorus pentoxide at a temperature of 80°C overnight. However, a cadmium complex of phosphatidylcholine hydrolyzate was obtained with a yield of 56%.

Production of polymerizable lipids by esterification Egg yolk reticin hydrolyzate cadmium complex 6.74g
160 ml of chloroform immediately after distillation was added to the solution and suspended under stirring. Add to this tung oil fatty acid anhydride 24.70
g and a catalyst. After adding 5.61 g of 4-dimethylaminopyridine and purging the inside of the container with argon gas, the container was tightly stoppered and reacted in the dark with stirring at a temperature of 25° C. for 60 hours. At this time, a white insoluble substance was precipitated, which was filtered and the solvent was distilled off under reduced pressure at room temperature, followed by methanol/chloroform/water=5/4/
1. Redissolve in 100ml of mixed solvent. This solution was filtered again and the filtrate was collected using ion exchange resin AG-501-X8.
(D) (Bio-Red) It was injected into a column and washed off with 500 ml of the above mixed solvent. After distilling off this solvent under reduced pressure at a temperature of 250°C, it was redissolved in chloroform and purified using a silica gel column.
% yield of phosphatidylcholine eleostearate was obtained. Its infrared absorption spectrum is
It was as shown in Figure 1.

Production of liposomes from polymerizable phospholipids Phosphatidylcholine eleostearate 200
mg was dissolved in 6 ml of chloroform. The lipid solution thus obtained was placed in an eggplant-shaped flask, and the solvent was completely removed using an evaporator to form a lipid film on the bottom of the eggplant-shaped flask. After adding 10 ml of Hepes buffer (10 mM, PH8.0) to this and shaking it with a vortex mixer, the mixture was treated with a tip-type ultrasonic irradiator (40 to 50 W) under an argon stream for 10 minutes. The treatment liquid changed from a cloudy state to a transparent dispersion, and the formation of liposomes was confirmed. Furthermore, spherical particles with a diameter of 0.2 to 0.5 μm were observed using a scanning electron microscope, confirming the formation of liposomes.

Example 1 A 1% by weight methanol solution of phosphatidylcholine eleostearate obtained in the above reference example was applied to a polystyrene tissue culture shear dish and dried. 75W for this polystyrene shear
Ultraviolet irradiation was performed using a mercury lamp in air at room temperature for 6 hours. After thoroughly washing the shear dish with distilled water, the contact angle of water droplets on the surface of the polystyrene shear dish was measured. The contact angle was 66° in the control polystyrene Schare without the polymerized coating of phosphatidylcholine eleostearate.
The contact angle of the surface of the shear coat treated as described above was 21°.

Example 2 A 1% by weight methanol solution of phosphatidylcholine eleostearate obtained in the above reference example was applied onto a polystyrene tissue culture shear dish and dried. For this polystyrene shear,
Ultraviolet irradiation was performed for 12 hours at room temperature in a nitrogen atmosphere using a 75W mercury lamp. In this polystyrene shearle
Adjusted to 1×10 ⁵ cells/ml in MEM medium.
5 ml of Hela-S3 cell suspension was dispensed and cultured for 48 hours. After 48 hours, the surface of the sheared surface was observed under a microscope, and it was confirmed that the cells had engrafted, spread, and proliferated.

Example 3 A chloroform solution containing 500 mg of phosphatidylcholine eleostearate obtained in the above reference example was placed in a 100 ml eggplant-shaped flask, and the chloroform was distilled off under reduced pressure using a rotary evaporator to coat the inner surface of the flask with eleostearin. A thin film of acid phosphatidylcholine was formed. This was left in the dark at room temperature for one week. As a result, phosphatidylcholine eleostearate was polymerized and gelled by oxygen in the air, and became completely insoluble in organic solvents such as chloroform, ether, and methanol, and in water.

Example 4 A hepes buffer suspension containing 1% by weight of the liposome of eleostearate phosphatidylcholine obtained in the above reference example was applied onto a glass shear dish and dried. This was irradiated with ultraviolet rays for 6 hours in air at room temperature using a 75W mercury lamp. As a result, it was confirmed that a film completely insoluble in water and organic solvents such as chloroform, ether, and methanol was formed on the surface of the sheared surface.

Separately, liposomes were added at a sample concentration of 10mg/
ml, and the irradiation distance using a 75W mercury lamp as the light source.
When the sample was irradiated with ultraviolet rays in a deaerated water bath with a water temperature of 25℃ as a 12cm sample, as shown in Figure 2, the absorbance at 272nm based on triene decreased with the passage of irradiation time, indicating that polymerization was progressing. was confirmed.

Specific Effects of the Invention As described above, the present invention provides hydrophobic acyl chains on the surface of at least the parts that come into contact with living bodies.
Since it is a medical device characterized by having a hydrophilic surface formed by forming a polymerized film of a polymerizable lipid having at least one acyl chain derived from eleostearic acid represented by the general formula (), it is suitable for living organisms, i.e. Surfaces that come into contact with tissues or body fluids, etc.
It is composed of polymerizable lipids that have a structure almost similar to the components that make up biological membranes, and its surface is hydrophilic, so it is extremely biocompatible, and the surface is cross-linked and polymerized. Because it is in the form of a polymeric film, it is in a stable state, and it is an extremely excellent medical device without causing any change even when it comes into contact with a living body during use or with a solvent or the like before use. In addition, the polymerizable lipids constituting such a polymer film are
Since it can be synthesized easily, in large quantities, and at low cost using naturally-obtained eleostearic acid and naturally-obtained lipids as starting materials, there is a risk that the final product, a medical device, will be limited in terms of quantity and cost. Nor. Furthermore, after applying the polymerizable lipid to the surface of the medical device using an appropriate method, the medical device irradiates the coated surface with electromagnetic waves such as light, ultraviolet rays, β rays, γ rays, and X-rays, and/or contacts the surface with oxygen. It can be produced by a simple method of cross-linking polymerizable lipids to form a polymer film, and in particular, it can also be produced only by contacting with oxygen.
For example, medical devices that require the formation of a polymeric film on areas where electromagnetic waves such as ultraviolet rays cannot reach, such as the inner surface of catheters, which was not possible using conventional polyacetylene-type lipids, or that are susceptible to deterioration due to electromagnetic irradiation. It is possible to provide a medical device having excellent biocompatibility even in the case of a medical device constructed of a material that is likely to cause an accident.

Such effects can be obtained when the polymerizable lipid having at least one acyl chain derived from eleostearic acid represented by the general formula () is eleostearic acid phospholipid, more preferably eleostearic acid phosphatidylcholine. becomes more prominent.

[Brief explanation of drawings]

Figure 1 is a chart of an infrared absorption spectrum of an example of a polymerizable lipid constituting the polymerized coating of the medical device of the present invention, and Figure 2 shows the degree of polymerization of this polymeric lipid in liposome form by ultraviolet irradiation. This is a chart of the absorption spectrum.

Claims (1)

[Claims] 1 At least on the surface of the site that comes into contact with the living body, as a hydrophobic acyl chain, a compound of the general formula () A medical device characterized by having a hydrophilic surface formed by forming a polymerized film of a polymerizable lipid having at least one acyl chain derived from eleostearic acid represented by: 2 The polymerizable lipid has the general formula () [However, in the formula, R is −(CH ₂ −) ₂ N (CH ₃ ) ₃ , −(
CH ₂ −) ₂ N H ₃ or −CH ₂ −CH(NH ₃ )−
He is the COO. ] The medical device according to claim 1, which is made of a phospholipid represented by the following. 3 R in general formula () is -(CH ₂ -) ₂ N (CH ₃ ) ₃
The medical device according to claim 2. 4. The medical device according to any one of claims 1 to 3, wherein the polymeric film is formed by cross-linking and polymerizing polymerizable lipids by irradiating electromagnetic waves. 5. The medical device according to any one of claims 1 to 3, wherein the polymeric film is formed by crosslinking and polymerizing a polymerizable lipid by bringing it into contact with oxygen. 6. The medical device according to any one of claims 1 to 3, wherein the polymeric film is formed by crosslinking and polymerizing a polymerizable lipid by exposing it to electromagnetic waves and contacting it with oxygen.