JPH0622591B2 - Method for manufacturing blood contact medical device - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a blood contact medical treatment in which a blood contact portion is made of a novel antithrombotic material having a remarkably excellent antithrombotic property, which is formed by forming an interpenetrating network structure of polyurethane and a crosslinked silicon-containing polymer. The present invention relates to a method of manufacturing a device.

Conventionally, polydialkylsiloxane-polyurethane block copolymers have been known as polydialkylsiloxane-polyurethane antithrombogenic substances (Japanese Patent Publication No.
9-29350, JP-B-55-8177), the former proposes a block copolymer in which a polyurethane block and a polydialkylsiloxane block are bonded by a silicon-nitrogen bond. On the other hand, in the latter case, it is argued that the antithrombogenicity is exhibited when the blood contact surface coated with the polydimethylsiloxane-polyurethane block copolymer has a micro-heterogeneous structure in which particles having a diameter of 0.1 to 3 μ are dispersed almost uniformly. , It is preferable that the polymer substance is a block copolymer in order to have such a micro heterogeneous structure. Further, it is said that the above block copolymer exhibits far superior antithrombotic properties than polydimethylsiloxane and polyurethane homopolymer.

All of these conventionally known antithrombogenic materials are produced by using a polyurethane polymer or polysiloxane polymer as a starting material. That is, in the antithrombotic material by a known blend (mixture), the starting materials, polyurethane and polysiloxane, are provided as polymers, respectively, while in the case of a copolymer, even random copolymerization is possible. In the case of a block copolymer or a graft copolymer, the block units constituting the copolymer are high molecular weight polymers.

The present inventor, while searching for an antithrombogenic material of polyurethane-silicon-containing polymer system, found an epoch-making method for producing an antithrombotic material by a method completely different from the conventionally known technique, and completed the present invention.

The present invention provides a method for producing a blood contact medical device in which a blood contact part is composed of a novel antithrombotic material in which a polyurethane and a crosslinked silicon-containing polymer form an interpenetrating network structure. The present inventor has found that the substance produced by this method is novel, which is not found in the known art, and exhibits an excellent antithrombotic property.

The present inventor was conceived not to be a mere blend of polyurethane and a silicon-containing polymer, but to form an interpenetrating network structure between the both polymers to express a microdomain structure in which both polymers are entangled with each other, To a solution of polyurethane dissolved in a solvent, a solution containing a low-molecular silicon-containing compound capable of converting into a cross-linked polymer by generating a cross-linking ability by a suitable method is prepared.
The present invention was attempted by embodying the above idea by forming a film on the film. As the silicon-containing polymer used in the present invention, a polysiloxane is most preferable as a silicon-containing polymer from a low-molecular silicon-containing compound having a functional group which is activated by water to generate a crosslinking ability (hereinafter referred to as a silicon-containing crosslinking agent).

As the silicon-containing cross-linking agent used in the present invention, a so-called room temperature cross-linking agent or a silane coupling agent usually used in the production of silicone resins and the like can be used. These are low molecular weight compounds and are soluble in the solvent of the above polyurethane, so that the polyurethane solution containing the silicon-containing crosslinking agent can be obtained as a uniform transparent solution. In this respect, the present invention is largely different from the polyurethane-polysiloxane mixed system solution composition already proposed. Since the polyurethane-polysiloxane mixed system does not dissolve in each other, micro phase separation occurs and the solution It has been known that the polysiloxane in the composition is dispersed as fine particles to form emulsion, which causes a problem in stability of the composition. Since these are emulsions in which the two components are microscopically dispersed, the solution is opaque and cloudy, and the polyurethane and polysiloxane dope is usually 0.1 to 50 .mu.m.

On the contrary, in the solution composition used in the present invention, the silicon-containing crosslinking agent has a low molecular weight and is completely compatible with polyurethane. This system can be considered to be one in which polyurethane is dissolved in a mixed solvent system consisting of a polyurethane solvent and a silicon-containing crosslinking agent, and the silicon-containing crosslinking agent is characterized in that it is mixed with polyurethane molecules on a molecular order. is doing.

In the present invention, it is preferable to dehydrate the water of the system as much as possible to make it anhydrous. When a silicon-containing cross-linking agent activated by water is used, as long as the silicon-containing cross-linking agent is kept anhydrous. It remains inactive and extremely stable over time.
When the solution is formed into a film, as the solvent evaporates, the high boiling point silicon-containing cross-linking agent remains in the film formation, and the amount of the solvent decreases due to evaporation. Aggregate to form independent microdomains, absorb moisture in the air and activate the functional groups in the crosslinker to cause mutual condensation reaction, and finally the crosslinker becomes crosslinked polysiloxane. Change. The polysiloxane thus produced constitutes micro domains and
Naturally, polyurethane molecules are entangled therein to form an interpenetrating network structure.

In the practice of the present invention, water may be intentionally added to activate the silicon-containing cross-linking agent immediately before film (thin film) molding (by a method such as casting, coating, dipping, spraying, etc.). The surface of the film thus produced shows a surprisingly high degree of antithrombotic property as described in the later examples, and since it is a transparent and homogeneous solution by nature, the film surface is smooth without any unevenness. This is in sharp contrast to the surface of a film formed from a mixed system of polyurethane and polysiloxane, which has 0.1 to 50μ of protrusions and depressions, and this smooth smooth surface also serves as an antithrombosis. It seems to have contributed.

In the present invention, as these silicon-containing crosslinking agents, those having a functional group activated by water are used.
Typical examples of these functional groups are ≡SiO-COCR,
≡Si—OR (R: CH ₃ , C ₂ H ₅ , C ₃ H ₇ , C ₄
Hydrocarbons), ≡Si-OX such as H _9, ≡Si-X
(X: halogen such as Cl and Br), ≡Si—NR
₂ (R: same as above). The crosslinked silicon-containing polymer produced when such a silicon-containing crosslinking agent is used has a polysiloxane structure.

A feature of the present invention is that, as a silicon-containing compound having a crosslinkability, the silicon atom has two hydrocarbon groups, and the molecule has a functional group that is activated by water to generate a crosslinkability. For example, general formula (I) (In the formula, R _{1 to} R ₄ are the same or different hydrocarbon groups, n is a positive integer such as 0, 1, 2, 3 and Y and Y ′ are crosslinks activated by the same or different water. A silicon-containing compound represented by the formula (1) and a silicon-containing compound [component (1)] having at least three crosslinkable functional groups in the molecule as an essential component. ], For example, the general formula
(II), (III) and (IV) (Wherein R ₁ is the same as above, Y, Y ′, Y ″ and Y represent a crosslinkable functional group which is activated by the same or different types of water), RnY _3-n —Si—O—Si —RmY ′ _3-m (IV) (wherein R is the same or different hydrocarbon group, Y and Y ′ are the same as above, n and n are 0, 1, 2, 3 and n + m = 0,
Which represents an integer of 1, 2, or 3) is used in the form of a mixture with at least one crosslinkable compound represented by

Hydrocarbons that are activated by water and exert a crosslinking ability to form a silicon-containing crosslinked polymer having a polysiloxane structure, which is the first component (1) and has two non-crosslinkable silicon atoms. Examples of the silicon-containing compound containing a group and two crosslinkable functional groups in the molecule include dimethyldiacetoxysilane, diethyldiacetoxysilane, dimethyldiethoxysilane, dimethyldimethoxysilane, diethyldiethoxysilane, diethyldimethoxysilane, Methylethyldimethoxysilane, dimethyldichlorosilane, methylphenyldiacetoxysilane, diphenylacetoxysilane, dibenzylacetoxysilane, divinyldiethoxysilane, 1,1,3,3-tetramethyl-1,3-dimethoxysilane,
1,1,3,3-tetraethyl-1,3-diacexisilane, 1,1,
3,3-tetomethyl-1,3-diethoxysilane, 1,1,3,3,5,
5-hexamethyl-1,5-diacetoxysilane, 1,1,3,3,
5,5-hexaethyl-1,5-diethoxysilane, 1,1,3,3,
5,5-hexamethyl-1,5-dimethoxysilane, 1,1,1,5,
5,5-hexamethyl-3,3-diacetoxysilane, 1,1,1,
3,5,5-Hesasamethyl-3,3-diacetoxysilane and the like can be mentioned.

A silicon-containing compound having one silicon atom in the molecule, which is activated by water as the component (2) and exerts a crosslinking ability to form a crosslinked polysilosan, is represented by the above general formulas (II) and (III). (Wherein R ₁ is a hydrocarbon group such as an alkyl group, an allyl group, an alkenyl group, an aryl group and an arylalkyl group, and Y, ′, Y ″ and Y are an alkoxy group, an acyloxy group, a halooxy group, halogen or Specific examples of (such as an amine acid group are preferable) are, for example, tetraacetoxysilane, methyltriacetoxysilane, ethyltriacetoxysilane, propyltriacetoxysilane, butyltriacetoxysilane, phenyltriacetoxysilane, and methyltriethoxysilane. , Ethyltriethoxysilane, tetraethoxysilane, phenyltriethoxysilane, propyltrieth Xysilane, butyltriethoxysilane, methyltriethoxysilane, tetramethoxysilane, ethyltrimethoxysilane, propyltrimethoxysilane, butyltrimethoxysilane or tetrachlorosilane, methyltrichlorosilane, ethyltrichlorosilane, butyltrichlorosilane, vinyltriacetoxysilane. , Bis- (N-methylbenzylamide)
Representative examples include ethoxymethylsilane, tris- (dimethylamino) methylsilane, tris- (cyclohexylamino) methylsilane, vinyltrichlorosilane, vinyltriethoxysilane, γ-glycidoxypropyltrimethoxysilane, and tetrapropoxysilane. it can. Typical examples of the silicon-containing compound represented by the above general formula (IV) containing two silicon atoms in its molecule include, for example, tetraacetoxydisiloxane, 1,3-dimethyltetraacetoxydisiloxane, 1,3- Examples thereof include divinyltetraethoxydisiloxane.

Examples of silicon-containing compounds containing three silicon atoms in the molecule include 1,3,5-trilimethoxy-1,1,3,5,5 pentamethyltrisiloxane, 1,1,3,3,3 5,5-hexaacetoxy-1,5
-Methyltrisiloxane etc. can be mentioned.

These silicon-containing compounds are known room temperature cross-linkable silas.
Coupling agents are widely used, for example petrarch.
Catalog issued by Petrarch System Inc.
Silicon Compounds, Register & Review 1979 and the same
Company Silicones Requirements for the first half of 1981
A silicon-containing compound satisfying the above can be used.

The silicon-containing compounds of the component (1) and the component (2) are not necessarily limited to one kind and may be a mixture of two or more kinds. Further, two or more kinds of silicon-containing compounds having different reactive groups may be used.

An important feature of the present invention is that the silicon-containing cross-linking agent is in a low-molecular inactive state in the solution composition, and the cross-linking functional group is activated immediately before or during the film formation to cause a cross-linking reaction, and to cause condensation. A reaction occurs to polymerize and change into a silicon-containing polymer compound having a polysiloxane structure, and these form a polyurethane and an interpenetrating network structure as a result of cross-linking, and the polyurethane and the cross-linked silicon-containing polymer have their respective micro domains. To form.

The crosslinked silicon-containing polymer produced in the present invention has a polysiloxane structure. In the present invention, the silicon-containing polymer contains a polydiorganosiloxane component having two hydrocarbon groups in the silicon atom. Is characterized by. That is, it is characterized in that it forms the most hydrophobic silicon-containing polymer. This indicates that the already-obtained cross-linked silicon-containing polymer microdomains are remarkably hydrophobic, and the prominent hydrophobic microdomain structure probably contributes to the development of excellent antithrombotic properties. It seems to be.

The blood contacting medical device obtained by the method of the present invention in which the blood contacting surface is constituted by such an antithrombogenic material has at least the above-mentioned polyurethane having a blood contacting portion and the crosslinked silicon-containing polymer having an interpenetrating network structure. It is composed of the formed antithrombotic material.

The blood contacting medical device obtained by the production method of the present invention should have at least its blood contacting portion composed of an antithrombotic material obtained by using the solution composition used in the present invention, and other materials other than the portion. It may be formed of. Since the anti-hematological material obtained by using the solution composition used in the present invention exhibits an antithrombotic property which can be said to be astonishing, it is used as a blood contact medical device obtained by the production method of the present invention in which the blood contact part is composed of this material. Includes all types of blood contact medical devices such as artificial hearts, blood circuits such as artificial kidney circuits and artificial heart-lung circuits, indwelling catheters, cannulas, various blood bypass tubes, blood bags and the like.

The blood contacting medical device obtained by the production method of the present invention has a blood contacting surface formed by bringing a solution in which polyurethane and a silicon-containing compound are uniformly dissolved into contact with the blood contacting surface to form a coating film. Is. As a method of contact, known methods such as casting, dipping, coating, and spraying can be used, and there is no particular limitation. By sufficiently converting the cross-linking agent in the film into the cross-linked silicon-containing polymer, the blood contact surface is formed.

The method for producing the blood contact medical device of the present invention will be described in detail.

In the present invention, polyurethane is first dissolved in a solvent. In this case, it is preferable to dehydrate the solvent as much as possible. Any solvent may be used as the solvent as long as it can dissolve polyurethane. The silicon-containing crosslinking agent mixture used in the present invention is added to this solution. The term "silicon-containing cross-linking agent" as used herein refers to a compound having one or more silicon atoms in its molecule and having the above-mentioned functional group that is activated by water to produce a cross-linking ability. Known compounds known as room-temperature crosslinking agents for silicone resins and silane coupling agents are widely used.

The polyurethane used in the present invention is not limited at all, and may be polyester type polyurethane and polyether type polyurethane.

Polyester polyurethanes are, for example, glycols such as ethylene glycol and diethylene glycol, or polyhydric alcohols such as trimethylolpropane and glycerin, and polyhydric carboxylic acids such as adipic acid and succinic acid to synthesize polyesters having terminal hydroxyl groups, and ethylene. Diisocyanate, 2,4-tolylene diisocyanate, 4,4'-diphenylmethane diisocyanate, etc. are reacted with an isocyanate group-containing compound that has been conventionally used in the production of polyurethane to give a prepolymer having isocyanate groups at both ends. Alternatively, it may be prepared by chain extension with a known chain extender.

In addition, the polyether polyurethane is obtained by reacting, for example, polyethylene glycol, polypropylene glycol or a copolymer thereof tetramethylene glycol, polytetramethylene glycol or alkylene oxide with polyhydric alcohol such as propylene glycol and 1,2,6-hexanetriol. Alternatively, the resulting polyol may be reacted with the above-mentioned isocyanate group-containing compound to form a terminal isocyanate prepolymer, which may be prepared by extending the molecular chain with a known chain extender.

When preparing the polyurethane used in the present invention,
Diamines as chain extenders, for example ethylenediamine,
Polyurethane urea may be prepared by using diethylenediamine or hexamethylenediamine. Of course, a known diol such as ethylene glycol or butanediol may be used as the chain extender.

The most preferred polyurethane is a polyether polyurethane or polyether polyurethane urea having a soft segment of polyethylene glycol, polypropylene glycol or polytetramethylene glycol having a molecular weight of 800 to 2500.

The solvent used in the present invention is an organic polar solvent such as cyclic ethers or dimethylformamide, dimethylacetamide, or dimethylsulfoxide that dissolves polyurethane, and from the viewpoint of reaction to a medical device, removal of the solvent from the coating film (evaporation) , Easy to wash with water, etc.,
The boiling point is preferably low, and the boiling point is 160 ° C. or lower, more preferably 110 ° C. or lower. Further, a water-soluble solvent is desirable because it can be easily washed and removed.

Therefore, preferable cyclic ethers include tetrahydrofuran, dioxane and the like.

In the present invention, the solvent may be used alone or in combination. It is most preferable to use a mixture of tetrahydrofuran and dioxane because of providing excellent antithrombogenicity and easy application and solvent removal. The weight ratio of dioxane / tetrahydrofuran is preferably 1 or less, more preferably 1/1 to 1/4, further preferably 1 / 1.5 to 1 /.
3.0. When it is more than 1, the solubility of polyurethane is lowered, and when it is less than 1/4, it is difficult to control the evaporation rate of tetrahydrofuran (low boiling point), and it is difficult to set conditions for obtaining a preferable surface. The excellent antithrombogenicity when the dioxane / tetrahydrofuran mixing ratio is in this range is considered to be due to the delicate influence of the evaporation rate and surface formation of the solvent in this range.

The ethers may contain a small amount of other solvents such as alcohol, acetone, dimethylformamide, etc. within a range that does not significantly affect the practice of the present invention. The mixing ratio of the polyurethane and the silicon-containing crosslinking agent can be widely changed. That is, the amount of the silicon-containing crosslinking agent in the mixture was 100 parts by weight of polyurethane.
It can be used in the range of 0.1 to 200 parts by weight, and preferably 1.0 to
180 parts by weight, more preferably 1.5 to 160 parts by weight, still more preferably 2.0 to 150 parts by weight, still more preferably 20.
Parts to 120 parts.

The amount of silicon-containing crosslinking agent is 100 parts by weight of polyurethane.
When the amount is less than 0.1 parts by weight, no difference is recognized as compared with the case of using polyurethane alone, and the mechanical performance of the film in which the amount of the silicon-containing crosslinking agent exceeds 200 parts by weight is poor, which is not preferable.

The silicon-containing cross-linking agent used in the present invention is cross-linked by being activated by a silicon-containing compound having two hydrocarbons in the silicon atom [the above-mentioned component (1)] and at least three water in the molecule. The weight ratio [component (1) / component (2)] of the silicon-containing compound [component (2)] exhibiting the ability is in the range of 95/5 to 5/95, preferably 90/10 to 10 / 90. This ratio is 95
If it exceeds / 5, the silicon-containing compound does not sufficiently cross-link and condense after being coated with the antithrombotic agent and remains in a liquid state, and the silicon-containing polymer may be separated from the coating surface by water, which is inconvenient. Cause This ratio is 5/9
When it is less than 5, the antithrombogenicity may vary because the hydrophobicity of the silicon polymer decreases.

The concentration of polyurethane in the polyurethane solution in which the silicon-containing crosslinking agent used in the present invention is dissolved is 1 to 50% by weight, preferably 3 to 40% by weight, more preferably 5 to 40% by weight.
It is 30% by weight, more preferably 8 to 20% by weight. If the polyurethane concentration is lower than this range, the viscosity is too low, which causes problems such as an increase in the number of coatings during film formation and the thinness of the formed film. If it exceeds this range, the viscosity is too high and it is difficult to adjust the film thickness. Therefore, the thickness of the coating film becomes uneven.

As described above, the blood contact portion is coated with the solution used in the present invention by the known contact method, and the coating film is formed by evaporating the solvent. The temperature for evaporating the solvent is not particularly limited as long as bubbles are not formed in the coating film or the blood contact portion is dissolved and deformed by the coating solution, but is preferably in the range of room temperature to 60 ° C. Moisture is indispensable for activating the silicon-containing cross-linking agent during film formation to promote cross-linking. Usually, moisture in the air is sufficient, but if water can be replenished, the humidity is 0 ( (For example, in a nitrogen stream) ~
65% R.I. H. Is preferred. In order to promote the crosslinking of the crosslinking agent in the presence of water, water is sprayed on the formed coating surface, or the blood contact part is immersed in water to perform hydration, and the temperature is from room temperature to 100 ° C. Usually within 1 hour ~
Sufficiently carry out crosslinking and condensation in the range of 1 month.

In this way, a blood contact medical device having a blood contact portion composed of an antithrombogenic material in which polyurethane and a crosslinked silicon-containing polymer form an interpenetrating network structure is manufactured.

According to the present invention, the above-mentioned silicon-containing cross-linking agent having a cross-linking ability is dissolved in a polyurethane solution, and a film is formed from this solution by a suitable method to form a blood contact part. It is characterized by forming microdomains of the crosslinking agent and activating the crosslinking reaction to cause a three-dimensional addition or condensation reaction to form an interpenetrating network structure of the crosslinked silicon-containing polymer and polyurethane. is there.

The formation of the interpenetrating network structure (referred to as IPN) in the present invention forms a crosslinked polymer (II) from a linear polymer (I), which is one of the general methods for forming an interpenetrating network structure. A method of dissolving in a monomer to form a crosslinked polymer (II) [for example, ENCYCLOPEDIA OF POLMER SCIENCE AND TECHNOLO
GY, Supplement 1, Vol. 288-306 (1976, John
Wiley & Sone))), wherein a linear polyurethane and a crosslinked silicon-containing polymer form an interpenetrating network structure.

In the production method of the present invention, the surface formed from a polyurethane solution containing a silicon-containing cross-linking agent not only exhibits antithrombotic properties which can be said to be quite anomalous, but the film is a strong string and also has excellent elasticity. Since it has properties, it is suitable for forming a blood contacting portion that constantly beats like an artificial heart or an intra-aortic balloon pump.

The present invention will be specifically described below with reference to examples.

The examples given below are for illustration only and are not intended to limit the invention in any way.

Example 1 100 parts by weight of a polyether polyurethane prepared by a known method using polypropylene glycol (average molecular weight 2100) and methylenebis (4-phenylisocyanate) and ethylenediamine as a chain extender was used to obtain a water content of 7 parts.
The mixture was dissolved in a mixed solvent of dioxane / tetrahydrofuran dehydrated to ppm or less (weight mixing ratio of 1/2) at 35 ° C. under stirring to prepare a viscous solution (polymer concentration 10% by weight). This solution finally contained 9.2 ppm of water.

A dimethyldiacetoxysilane / methyltriacexysilane mixture immediately after distillation (mixing ratio 95/5, 90
/ 10, 80/20, 70/30, 50/50, 20 /
80, 5/95, 3/97) is 1, 2, 4, 6, 8, 12, 14, 20, 3 per 100 parts by weight of polyurethane.
0, 40, 50, 60, 75, 80, 100, 120,
140, 160, 180 and 200 parts by weight were added respectively to prepare a coating solution.

1- (1), 1- (2), ..., 1- (10)
And so on.

All of these solutions were colorless and transparent and remained stable even after storage for one month.

Speaking of the film formed on the glass plate from these solutions, the film formed from Solution 1- (1),-(2),-(3) is almost colorless and transparent, and from Solution 1- (4). The film thus formed is slightly opalescent, and the whitening degree increases as the content of the silicon-containing crosslinking agent in the solution increases.

When these surfaces were observed with a scanning electron microscope, they were extremely smooth.

Using these films, a white test (Clinical Test Method Recommendation VI-86, edited by Izumi Kanai and Masamitsu Kanai, published by Kanehara Publishing Co., Ltd.) was performed to measure blood coagulation time. The results are shown in Table 1. For reference, glass, silicone-treated (coated with polydimethylsiloxane) glass, and polyurethane results of this example are also shown. The test film was prepared by coating a glass watch glass with each of the above-mentioned solutions and leaving it in an atmosphere of room temperature and 65% RH for 10 days or more to sufficiently cross-link dimethyldiacetoxysilane and methyltriacetoxysilane.
It was submitted to the test.

As shown in Table 1, as a result of the Lee White test, the solution 1-
It was found that when (14) to (20) were used, blood did not coagulate for 180 minutes or more, and had epoch-making performance beyond the conventional wisdom.

Example 2 A polyethylene polyurethane was prepared by using polyethylene glycol (average molecular weight 1800) and tolylene diisocyanate and butanediol as a chain extender. 100 parts by weight of this polyether polyurethane was dissolved in sufficiently dehydrated dioxane tetrahydrofuran (weight ratio 1/3) at room temperature with stirring to obtain a viscous solution having a polymer concentration of 9.0%. A mixture of dimethyldimethoxysilane and methyltrimethoxysilane was added to this solution at a ratio shown in the following table to obtain a uniform transparent solution. As in Example 1, the results obtained by performing the white-white test on the film and the test tube which were cast on a glass plate to form a film are summarized in Table 2.

Example 3 Commercially available polyether polyurethane (Ethicon product Bio
mer) of 12% by weight in dimethylacetamide was prepared and thoroughly dehydrated. To this solution, purified dimethoxydimethylfuran, tetramethoxysilane, and tetraethoxysilane immediately after distillation were added in the amounts shown in Table 3 to obtain 8 kinds of solutions. The white film test was carried out using films formed from these solutions. The results are also shown in Table 3.

Comparative Example 1 A film was formed into a film in the same manner as in Example 3 except that only 1 part by weight of tetramethoxysilane was added per 100 parts by weight of urethane, and a white test was performed using this film. The results are also shown in Table 3.

Example 4 To the same polyurethane solution as in Example 1 was added diacetoxydimethylsilane and tetraacetoxysilane in the amounts shown in Table 4 (parts by weight per 100 parts by weight of polyurethane), and 6
A seed solution was obtained. The white film test was carried out using films formed from these solutions. The results are shown in Table 4.

Comparative Example 2 A film was formed in the same manner as in Example 4 except that only tetraacetoxysilane was added in the amount shown in Table 4, and a white test was performed using this film. The fourth result
It is also shown in the table.

Example 5 An artificial heart of the sask type was made of soft polyvinyl chloride.
The soft polyvinyl chloride contained 80% by weight dioctyl phthalate. The capacity of the artificial heart is 9
It is 0 ml.

The solutions obtained in Examples 1, 2, 3, and 4 were applied to the blood-contacting portion on the inner surface of each, and allowed to stand for two weeks or more in an atmosphere of a humidity of 65% RH for sufficient crosslinking, and goat was used for each. The left ventricular assist was performed at a low discharge rate of 1.0 or less per minute. In all cases, no thrombus formation was observed in the 3-week experiment.

On the other hand, for reference, in an experiment using a similar pump coated with a commercially available antithrombotic material Cardiosan 1, 2.0 /
Although the generation of thrombus was not observed in the case of discharge of more than 2 minutes, 2.0
When the discharge rate was less than 1 minute, a small amount of thrombus was found in a part of the suck, although there was almost no thrombus over the whole period after 1 week.

Claims (1)

[Claims] 1. A solution prepared by dissolving polyurethane in a solvent, which comprises (1) a functional group having two hydrocarbon groups on a silicon atom and having a crosslinkability when activated by two water in the molecule. A silicon-containing compound having (1) and (2) a weight ratio of (1) and (2) is 95/5. ~ 5/95 homogeneous solution, and using this solution to form a coating on at least the blood contact part of the blood contact medical device, and the above (1) and (2)
A method for producing a blood contact medical device, which comprises converting the above silicon-containing compound into a crosslinked silicon-containing polymer.