JPS62285917A - Polyester elastomer and its production - Google Patents

Abstract

PURPOSE:To make a polyester elastomer well applicable to a medical material by improving its moldability and mechanical properties and decreasing its interaction with the blood or the soft tissues of a living body, by introducing an organosilicon polymer part in the main chain of the polymer elastomer. CONSTITUTION:This polyester elastomer contains a diol compound part containing an organosilicon polymer part of an MW of 200-10,000 and a polyester of an MW >=500 and/or a polyester long-chain diol compound part (a) and a diol compound part of an MW <=300 (b) and a dicarboxylic acid compound part (c) as soft segments, wherein the content of said organosilicon polymer in said elastomer is 1-50wt%. The organosilicon polymer part containing a polydimethylsilicone part is desirable in respect of good balance between antithrombotic property and mechanical property.

Description

Detailed Description of the Invention 3 Detailed Description of the Invention [Industrial Field of Application] The present invention relates to a polyester containing an organosilicon polymer moiety in its main chain, which has the property of having little interaction with blood and biological soft tissue. Related to elastomers and their manufacturing methods.

[Prior Art] Polyester elastomers made of dicarboxylic acid compounds, short-chain diol compounds, and polyether or polyester-based long-chain diol compounds are widely used in industry because of their excellent moldability and mechanical properties. There is. In addition, in order to improve the coefficient of friction and slippage, polyesters using compounds containing polysiloxane moieties as long-chain diol compounds (Japanese Patent Publication No. 48-4117, Japanese Patent Application Laid-Open No. 58-1988)
No. 2325) is also known.

[Problems to be Solved by the Invention] However, these polyester elastomers or polyesters have a strong interaction with blood, biological soft tissue, etc., and therefore are not suitable as medical materials that come into contact with these.

The purpose of the present invention is to provide a polyester nylastomer that has excellent moldability and mechanical properties, has low interaction with blood and biological soft tissues, and is suitable for medical materials. The purpose of this invention was to provide a polyester elastomer with low antithrombotic properties and excellent antithrombotic properties.

[Means for Solving the Problems] The present invention is based on the discovery that the interaction with blood and biological soft tissues is reduced by incorporating an organosilicon polymer moiety into the main chain of a polyester elastomer. It contains a diol compound part containing an organosilicon polymer part with a molecular weight of 200 to 10,000 and a polyether and/or polyester long chain diol compound part with a molecular weight of 500 or more as a soft segment, and further has a molecular weight of A polyester elastomer containing a diol compound moiety and a dicarboxylic acid compound moiety of 300 or less, wherein the proportion of the organosilicon polymer moiety contained in the elastomer is 1 to 50% (wt%).
, hereinafter the same), a diol compound containing an organosilicon polymer moiety with a molecular weight of 200 to 10,000, a polyether and/or polyester-based long chain diol compound with a molecular weight of 500 or more,
The present invention relates to a method for producing a polyester elastomer by reacting a diol compound with a molecular weight of 300 or less and a dicarboxylic acid compound, the method for producing a polyester elastomer in which the proportion of the organosilicon polymer portion contained in the elastomer is 1 to 50%.

[Example] The organosilicon polymer moiety in this specification refers to an organosilicon in which an organic group such as an alkyl group, a phenyl group, an alkylphenyl group, a phenylalkyl group, or a fluorinated group of these groups is bonded to a silicon atom. A part that contains at least two groups and has silicon atoms at both ends. Although there is no particular limitation on the method of bonding silicon atoms, from the viewpoint of expressing antithrombotic properties, general formula (1) (wherein R1
, R2 is a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, a phenyl group, a phenyl group having an alkyl group having 1 to 10 carbon atoms, an alkylene group having 1 to 10 carbon atoms having a phenyl group, or a fluorine group of these groups. R+ and R2 may be the same or different, n is 1
A polysiloxane moiety represented by the above integer is preferable. Among these, those containing a polydimethylsiloxane moiety are particularly preferred from the standpoint of having excellent antithrombotic properties and mechanical properties in a well-balanced manner. Most preferably, the polydimethylsiloxane moiety is contained in the main chain of the polyester elastomer in the form of the following formula.

CH3CH3 1] CH3CH3 (wherein R3-R6 are all alkylene groups having 2 or more carbon atoms, preferably 2 to 6 carbon atoms such as ethylene group, propylene group, butylene group, hexamethylene group, axe is 0 to 3
0. Preferably an integer of 0 to 2°, bSd is 0 or 1,
C is an integer from 2 to 134. ) Above, di: 0 or 1, but considering long-term use in the body, it is desirable that it does not contain S 1-0-C bonds that are susceptible to hydrolysis. It is preferable to have one. C is an integer from 2 to 134, determined by the selection of the molecular weight of the polydimethylsiloxane moiety. The molecular weight of the organosilicon polymer portion is 200 to 10,000
However, in consideration of the balance between mechanical properties and the property of having low interaction with blood and biological soft tissues, those with a molecular weight of 400 to 5,000 are preferable, and those with a molecular weight of 500 to 3,000 are particularly preferable. If the molecular weight of the organosilicon polymer portion is less than 200, the interaction with blood and biological soft tissue will not be sufficiently reduced, and if it exceeds 10,000, the mechanical properties will be poor or the interaction with blood and biological soft tissue will not be sufficiently reduced. It may disappear.

The proportion of the organosilicon polymer portion in the polyester elastomer of the invention is 1 to 50%, preferably 3 to 30%, particularly preferably 4 to 20%. If the proportion of the organosilicon polymer portion is less than 1%, the interaction with blood and biological soft tissue will not be sufficiently reduced, and if it exceeds 50%, the mechanical properties will deteriorate or the interaction with blood and biological soft tissue will be reduced. The effect is not small enough.

The organosilicon polymer portion having a molecular weight of 200 to 1000 as described above is contained as a portion of a diol compound, and the polyester elastomer of the present invention is produced using this diol compound.

The diol compound containing the organosilicon polymer moiety has the general formula (2): % formula % (21 (wherein A is the organosilicon polymer moiety,
f-(OR8)g-OII(R),I? a is an alkylene group having 2 or more carbon atoms, preferably 2 to 6 carbon atoms, f is O or 1
, g is an integer of O to 30), and may be the same or different. In order to obtain a polyester elastomer having excellent antithrombotic properties, it is further preferable to use a diol compound represented by the general formula (3): % formula %).

The polyether elastomer of the present invention contains, as a soft segment, a polyether and/or polyester-based long-chain diol compound portion having a molecular it of 500 or more, in addition to the diol compound portion containing the organosilicon polymer portion.

The soft segment as used herein refers to a residue obtained by removing hydrogen from the hydroxyl group of a diol compound containing an organosilicon polymer moiety or a polyether and/or polyester long-chain diol compound with a molecular mouth of 500 or more. be.

The long-chain diol compound is not limited to polyether and/or polyester long-chain diol compounds, but also includes diol compounds that are block polymers of polyether polyesters, and furthermore, the long-chain diol compounds include polyether and/or polyester long-chain diol compounds. The concept also includes compounds that are derivatives and can be used for esterification.

The two hydroxyl groups of the long-chain diol compound are preferably located at both ends of the molecule or as close to both ends of the molecule as possible, and the molecular weight is required to be 500 or more in order to have performance as an elastomer. 50
It is preferably 0 to 8000, especially 500 to 3
Preferably, it is 000. Furthermore, the long-chain diol compound moiety has excellent in-vivo hydrolysis resistance and thermal stability during production.
Taking into account the ease of polycondensation, polyethers are preferable to polyesters.

Specific examples of the long-chain diol compounds include polyethylene glycol, polypropylene glycol, polytetramethylene glycol, glycols composed of block polymers thereof, general formula (4): (wherein, R is a carbon 2-6 carbon Examples include polyethers such as diol compounds represented by an alkylene group (h is an integer of 1 or more, preferably 3 to 21), and polyesters such as polylactone. Considering stability against hydrolysis and ease of polycondensation, among these, polyethers are more preferable, and polytetramethylglycol and the glycol represented by general formula (4) are particularly preferable.

The dicarboxylic acid compounds used in the present invention include compounds that can form esters with dicarboxylic acids or derivatives thereof, such as aromatic dicarboxylic acids, aliphatic (including alicyclic, hereinafter the same) dicarboxylic acids, and these acids. Examples include halides and acid anhydrides, and dialkyl esters may also be used. Specific examples of the dicarboxylic acid compound include terephthalic acid, phthalic acid,
Isophthalic acid, 4,4-biphenyldicarboxylic acid, 4.
4'-sulfonyl dibenzoic acid, 2,6-naphthalene dicarboxylic acid, cyclohexane dicarboxylic acid, adipic acid,
One or a mixture of two or more of sebacic acid, succinic acid, fumaric acid, dialkyl esters, acid halides, and acid anhydrides thereof may be used. Among these, terephthalic acid and its dialkyl esters are more preferred from the viewpoint of good moldability and physical properties based on the crystallinity of the hard segment.

The diol compound with a molecular weight of 300 or less used in the present invention is a compound that can form an ester with a diol or its derivative with a molecular weight of 300 or less, and specific examples thereof include ethylene glycol, propylene glycol, 1.4- Butanediol, 1,3-butanediol, 2,3-butanediol, diethylene glycol,
Dipropylene glycol, triethylene glycol, 1
．． 5-bentanediol, 1,6-hexanediol,
Examples include neopentyl glycol and hydrogenated bisphenol A, and these may be used alone or in combination of two or more. Among these, ethylene glycol and 1,4-butanediol are preferred in order to obtain excellent mechanical properties. Furthermore, considering that the temperature required during polycondensation and molding is low and the crystallization rate is fast,
Particularly preferred is 1,4-butanediol.

If the molecular weight of the diol compound exceeds 300, the strength and moldability will be insufficient, which is not preferable.

The content ratio of the long chain diol compound part and the diol compound part containing the organic silicon polymer part in the polyester elastomer of the present invention is preferably 90/1 to 0.5, and more preferably 30/1 to 1/1. Preferably, 2
Particularly preferred is 0/1 to 2/1.

If the ratio exceeds 90/1, the interaction with blood and biological soft tissue will not be reduced, and if it is less than 0.5, the mechanical properties will deteriorate, and the interaction with blood and biological soft tissue will tend not to become small. .

Further, it is preferable that the molecular weights of the long-chain diol compound portion and the diol compound portion carrying the organosilicon polymer portion be approximately equal, in order to reduce interaction with blood, biological soft tissues, and the like.

The soft segment ratio ■ in the present invention is 10 to 90%
is preferable, and 20 to 80% is more preferable. If the soft segment ratio is small, the elastomer will be hard, and if it is high, the elastomer will be soft, and each can be used depending on the purpose. However, the soft segment ratio is 1
If it is less than 0%, the properties as an elastomer will be insufficient,
If it exceeds 90%, the strength tends to be poor and the moldability tends to be poor.

The polyester elastomer of the present invention can be produced using conventional and ordinary polyester manufacturing methods, such as direct esterification reaction using glycol and polybasic acid, direct esterification reaction using glycol and acid anhydride, and direct esterification reaction using dicarboxylic acid ester and glycol. It can be produced by various methods such as transesterification, polycondensation of dicarboxylic acid esters, metathesis reaction of dicarboxylic acid chloride and diol, and the like.

The most common of these is the transesterification reaction between dicarboxylic acid diester and glycol, so this method will be specifically explained.

In this method, raw materials are transesterified, and the transesterified products are polycondensed.

The synthetic raw materials may be charged all at once from the beginning, or diol compounds containing organosilicon polymer moieties and long-chain diol compounds with low heat resistance may be added during polycondensation.

In the transesterification reaction, for example, a dicarboxylic acid dialkyl ester, a diol compound with a molecular weight of 300 or less, a diol compound containing an organosilicon polymer portion with a molecular weight of 200 to 10,000, and a polyether and/or polyester long chain diol compound with a molecular weight of 500 or more are used. and in the presence of a catalyst in an inert gas atmosphere such as nitrogen gas for about 15
It is heated to 0 to 250°C. As a catalyst, known transesterification catalysts such as organotitanium compounds and compounds such as antimony, lead, zinc, magnesium, germanium, calcium or manganese can be used.

The polycondensation reaction is carried out under reduced pressure of about 1 mmHg or less and at a temperature range from the melting point of the resulting copolymer to 300°C, but considering the thermal decomposition of long-chain diol compounds and diol compounds containing organosilicon polymer moieties, Melting point of produced copolymer ~260
A range of 0.degree. C. is preferred.

Further, in this polycondensation reaction step, a compound such as lead, titanium, antimony, niobium, germanium, etc. may be added as a catalyst, if necessary.

The reduced specific viscosity (η/C) of the polyester elastomer of the present invention thus obtained is 0.5 to 3.0 (phenol/tetrachloroethane-1/1) from the viewpoint of practical strength. Measured at 25℃ using a mixed solvent with a polymer concentration of C-0.5g/dΩ (volume ratio))
It is preferable that it is, and it is more preferable that it is 0.7-2.0.

Polyester elastomers produced in this way can be used in medical devices that come into contact with blood or biological soft tissues by extrusion molding, injection molding, or coating.
For example, it can be suitably used for blood circuits, blood bags, catheters, blood pumps, blood transfusion sets, housings for various artificial organs, artificial blood vessels, sutures, and the like.

The present invention will be explained below using Examples.

In addition, "parts" in Examples and Comparative Examples mean parts by weight, and the reduced specific viscosity (η/C) is calculated using a mixed solvent of phenol/tetrachloroethane-1/1 (volume ratio) and the polymer concentration C. -0.5g/rHJ
, is a value measured at 25°C.

Example 1 19.4 parts of dimethyl terephthalate, 18 parts of 1,4-butanediol, 0.09 part of tetra-n-butyl titanate as a catalyst, antioxidant (Irganox 1330.
(manufactured by Ciba Geigy) O, Lll jacket temperature 160
The mixture was placed in an autoclave under a nitrogen gas atmosphere and stirred. The temperature was raised to 250°C over 100 minutes at normal pressure, and when the transesterification reaction was completed, 62 parts of polytetramethylene glycol with a molecular weight of 2,000 and polydimethylsiloxane (with a molecular weight of about 2,400
, the molecular weight of the polydimethylsiloxane portion is approximately 1080, and the molecular weight of the polyethylene glycol portion is approximately 880) 13
1,000 methanol, 1,000 methanol,
While removing 4-butanediol, the inside of the system was brought to 0.5a+mHg or less over 30 minutes, and polycondensation was continued for 100 minutes to obtain a polyester elastomer.

The reduced specific viscosity of this elastomer was 1.2. J.I.
A No. S3 dumbbell-shaped test piece was prepared and the tensile strength measured using Shimabara Autograph Is-2000 was 320 kg.
/cd, and the elongation was 710%.

Next, the interaction of this elastomer with blood was measured by the following method.

That is, a sheet of the elastomer was prepared, and 3<em>
It was cut into squares of 3 cm x 3 cm and placed on a watch glass with a lid maintained at 37°C. After placing a certain amount of dog ACD blood (preserved blood that has been made non-coagulable by adding sodium citrate, glucose, etc.) on the sheet and the glass of another watch glass, an aqueous calcium chloride solution is added, and a predetermined amount is added. The amount of coagulated blood (thrombus) was measured every time, and the final weight of the thrombus formed on the glass was determined. The results are shown in Table 1.

Comparative Examples 1 to 2 From the composition of Example 1, polydimethylsiloxane with polyethylene glycol at both ends was removed, and the molar amount of polytetramethylene glycol corresponding to this molar amount was increased, and the other conditions were the same as in Example 1. A polyester elastomer was produced, and the thrombus formation rate was determined in the same manner as in Example 1. The thrombus formation rate was also determined for glass.

The results are shown in Table 1.

[Margin below] From the results in Table 1, it can be seen that the sheet made of the polyester elastomer of the present invention has excellent antithrombotic properties.

Example 2 960 parts of dimethyl terephthalate, 810 parts of 1,4-butanediol, 375 parts of polytetramethylene glycol with molecule ffi 1025, -CIhCH2CHz-0-CH2CH2-Of ((average molecular weight 1030) 75 parts, tetra-n-butyl Titanate 1.5 parts, antioxidant (Irganox 1010
, manufactured by Ciba Geigy) at a jacket temperature of 200
The mixture was placed in an autoclave under a nitrogen gas atmosphere and stirred.

The temperature was raised to 250°C over 100 minutes at normal pressure, and methanol was removed by distillation. After reaching 250° C., the pressure was gradually reduced and polycondensation was carried out at 0.5a+ml or less in 30 minutes. Polycondensation reaction was carried out for 100 minutes to obtain a polyester elastomer.

The reduced specific viscosity of this elastomer was 1.0. J.I.
S No. 3 dumbbell type test piece was prepared and the expansion force determined by Igj using Shimabara Autograph 15-2000 was 4QQk
g/cd, elongation was 450%.

The interaction of this elastomer with blood was measured in the same manner as in Example 1. The results are shown in Table 2.

Comparative Examples 3 to 4 From the composition of Example 2 -CII2CH2C11z-0-CH2CH2-0ff
(average molecular weight 1030), the molar amount of polytetramethylene glycol (molecules ff
A polyester elastomer was produced under the same conditions as in Example 1, except that the amount of i 1025) used was increased, and the thrombus formation rate was determined in the same manner as in Example 1. The thrombus formation rate was also determined for glass. The results are shown in Table 2.

Example 3 In Example 2, instead of polytetramethylene glycol having a molecular weight of 1025, the same number of moles of polytetramethylene glycol having a molecular weight of 1000 was used.
When H3 was used, a polyester elastomer with a reduced specific viscosity of 069°5 was obtained.

Example 4 Instead of 1,4-butanediol in Example 3,
When the same number of moles of ethylene glycol was used and the temperature during polycondensation was set to 270°C, a polyester elastomer with a reduced specific viscosity of 0.86 was obtained.

[Effects of the Invention] When a sheet made of the polyester elastomer of the present invention comes into contact with blood or biological soft tissue, the interaction with these is small and exhibits excellent antithrombotic properties.

This property exists in a microphase-separated structure in which the soft segment becomes a hydrophobic domain and the 1-dosegment becomes a hydrophilic domain, and the organosilicon polymer part is included in a part of the soft segment. This is presumed to be due to a microphase-separated structure with low interaction. In addition, since the polyester elastomer of the present invention uses an organosilicon polymer part as a part of the soft segment, there is little deterioration in tensile strength and moldability, and it has a tensile strength comparable to that of a polyester elastomer that does not contain an organosilicon polymer part. Since it has moldability, it has excellent moldability in extrusion molding, injection molding, etc. Therefore, the polyester elastomer of the present invention can be used in medical devices that come into contact with blood and biological soft tissue, such as blood circuits, blood bags, catheters, blood pumps, and blood transfusion sets. , housing artificial blood vessels for various artificial organs,
It can be suitably used for sutures, etc.

Claims (1)

[Claims] 1. Molecular weight as a soft segment of 200 to 10,000
A diol compound portion containing an organosilicon polymer portion and a polyether having a molecular weight of 500 or more and/or
A polyester elastomer containing a polyester long-chain diol compound portion, and further containing a diol compound portion with a molecular weight of 300 or less and a dicarboxylic acid compound portion, wherein the proportion of the organosilicon polymer portion contained in the elastomer is 1 to 50% by weight. % polyester elastomer. 2 A polyester elastomer made by reacting a diol compound containing an organosilicon polymer portion with a molecular weight of 200 to 10,000, a polyether and/or polyester long chain diol compound with a molecular weight of 500 or more, a diol compound with a molecular weight of 300 or less, and a dicarboxylic acid compound. A method for producing a polyester elastomer, wherein the proportion of the organosilicon polymer portion contained in the elastomer is 1 to 50% by weight.