JPH0558445B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Field of Application] The present invention relates to a polyester elastomer containing an organosilicon polymer moiety in its main chain, which has the property of having little interaction with blood and biological soft tissue, and a method for producing the same. [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, polyesters using compounds containing polysiloxane moieties as long-chain diol compounds (Japanese Patent Publication No. 48-4117, Japanese Patent Application Laid-open No. 58-2325) are also known in order to improve the coefficient of friction and slippage. [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 elastomer that has excellent moldability and mechanical properties, has low interaction with blood and biological soft tissue, and is suitable for medical materials. This was developed with the aim of providing a polyester elastomer with low blood pressure and excellent antithrombotic properties. [Means for Solving the Problems] The present invention provides a solution by incorporating an organosilicon polymer moiety into the main chain of a polyester elastomer.
This was done based on the discovery that the interaction with blood and biological soft tissues is reduced, and as a soft segment, the general formula (1): (In the formula, R ₁ and R ₂ are 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 an organosilicon polymer moiety having a molecular weight of 200 to 10,000, which is a group obtained by fluorinating these groups, where R ₁ and R ₂ may be the same or different, and n is an integer of 1 or more. General formula (2) containing: X-A-Y (2) (wherein A is an organosilicon polymer moiety, X and Y are -
(R ₇ ) _f -(OR ₈ ) _g -OH (R ₇ and R ₈ are alkylene groups having 2 or more carbon atoms, f is 0 or 1, and g is an integer from 0 to 30), and the same and polyethylene glycol, polypropylene glycol, polytetramethylene glycol, a glycol consisting of a block polymer thereof, or general formula (3): (In the formula, R is an alkylene group having 2 to 6 carbon atoms, and h is an integer of 1 or more).
Polyester elastomers containing the following diol compound moieties and dicarboxylic acid compound moieties, in which the proportion of the organosilicon polymer moieties contained in the elastomers is 1 to 50% (wt%, the same shall apply hereinafter), and general polyester elastomers. Formula (1): (In the formula, R ₁ and R ₂ are 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 an organosilicon polymer moiety having a molecular weight of 200 to 10,000, which is a group obtained by fluorinating these groups, where R ₁ and R ₂ may be the same or different, and n is an integer of 1 or more. General formula (2) containing: X-A-Y (2) (wherein A is an organosilicon polymer moiety, X and Y are -
(R ₇ ) _f -(OR ₈ ) _g -OH (R ₇ and R ₈ are alkylene groups having 2 or more carbon atoms, f is 0 or 1, and g is an integer from 0 to 30), and the same diol compounds represented by (may be or may be different), polyethylene glycol, polypropylene glycol, polytetramethylene glycol with a molecular weight of 500 or more, glycols consisting of block polymers thereof, or general formula (3): (In the formula, R is an alkylene group having 2 to 6 carbon atoms, and h is an integer of 1 or more.) A method for producing a polyester elastomer in which a long-chain diol compound represented by the formula, a diol compound with a molecular weight of 300 or less, and a dicarboxylic acid compound are reacted. The present invention relates to a method for producing a polyester elastomer in which the proportion of the organosilicon polymer moiety contained in the elastomer is 1 to 50. [Example] The organosilicon polymer moiety in this specification refers to a silicon atom to which an organic group such as an alkyl group, a phenyl group, an alkylphenyl group, a phenylalkyl group, or a fusorated group of these groups is bonded. It is a part that contains at least two or more organosilicon groups and has silicon atoms at both ends. As for the bonding method of silicon atoms, from the viewpoint of antithrombotic properties, general formula (1) is used: (In the formula, R ₁ and R ₂ are 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) Alternatively, it is preferably a polysiloxane moiety which is a group obtained by fluorinating these groups, where R ₁ and R ₂ may be the same or different, and n is an integer of 1 or more. 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. (In the formula, R ₃ to _{R 6} each have 2 or more carbon atoms, preferably an ethylene group, a propylene group, a butylene group,
2 to 6 alkylene groups such as hexamethylene groups, a and e are integers of 0 to 30, preferably 0 to 20;
b and d are 0 or 1, and c is an integer from 2 to 134. ) The above b and d are 0 or 1, but considering long-term use in the body, Si-O is susceptible to hydrolysis.
It is preferable that it does not contain a -C bond, and from this point of view, it is preferable that b and d are 1. c is 2~134
, which is determined by the selection of the molecular weight of the polydimethylsiloxane moiety. The molecular weight of the organosilicon polymer portion is required to be between 200 and 10,000, but considering the balance between mechanical properties and the property of having little interaction with blood and biological soft tissues, those with a molecular weight of 400 to 5,000 are preferred. Preferably, 500 to 3000 is 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 disappears. The proportion of organosilicon polymer moiety in the polyester elastomer of the present invention is 1 to 50%, preferably 3 to 50%.
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, resulting in
If it exceeds %, the mechanical properties will deteriorate and the interaction with blood and biological soft tissues will not be sufficiently reduced. The organosilicon polymer portion having a molecular weight of 200 to 10,000 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):
(R ₇ ) _f −(OR ₈ ) _g −OH (R ₇ and R ₈ have 2 or more carbon atoms,
Preferably, it is a group represented by an alkylene group of 2 to 6, f is 0 or 1, and g is an integer of 0 to 30),
may be the same or different). In order to obtain a polyester elastomer with excellent antithrombotic properties, the general formula (4): It is preferable to use a diol compound represented by: The polyester elastomer of the present invention contains, as a soft segment, a polyether long-chain diol compound portion having a molecular weight 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 long-chain polyether diol compound having a molecular weight of 500 or more. The concept of the long-chain diol compound includes derivatives thereof that 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. It is preferably from 500 to 6,000, particularly preferably from 500 to 3,000.
Furthermore, polyethers are preferable from the viewpoint of in vivo hydrolysis resistance of the long-chain diol compound moiety, thermal stability during production, and ease of polycondensation. Specific examples of the long-chain diol compounds include polyethylene glycol, polypropylene glycol, polytetramethylene glycol, glycols composed of block polymers thereof, and general formula (3): (In the formula, R is an alkylene group having 2 to 6 carbon atoms, and h is an integer of 1 or more, preferably 3 to 21.) Polyethers such as diol compounds are exemplified. As the dicarboxylic acid compound used in the present invention,
Examples 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 their acid halides or acid anhydrides. It may also be a dialkyl ester. Specific examples of the dicarboxylic acid compound include terephthalic acid, phthalic acid,
Isophthalic acid, 4,4'-biphenyl dicarboxylic acid, 4,4'-sulfonyl dibenzoic acid, 2,6-naphthalene dicarboxylic acid, cyclohexane dicarboxylic acid, adipic acid, sebacic acid, succinic acid, sumalic acid, etc. One or a mixture of two or more of dialkyl esters, acid halides, acid anhydrides, etc. 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,
Examples include 5-pentanediol, 1,6-hexanediol, neopentyl glycol, 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 portion and the diol compound portion containing the organosilicon polymer portion in the polyester elastomer of the present invention is
The ratio is preferably 90/1 to 0.5/1, more preferably 30/1 to 1/1, and particularly preferably 20/1 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 0.5/1, the mechanical properties will deteriorate and the interaction with blood and biological soft tissue will not decrease. arise.
Furthermore, it is preferable that the molecular weights of the long-chain diol compound portion and the diol compound portion containing the organosilicon polymer portion be approximately equal, from the viewpoint of reducing interaction with blood, biological soft tissues, and the like. The soft segment ratio (%) (molecular weight of all soft segment parts/polyester elastomer molecular weight x 100) in the present invention is preferably 10 to 90%, more preferably 20 to 80. 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, when the soft segment ratio is less than 10%, the properties as an elastomer are insufficient, and when 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 by a conventional conventional polyester manufacturing method, such as a direct esterification reaction using a glycol and a polybasic acid.
It can be applied to various methods such as direct esterification reaction using glycol and acid anhydride, transesterification reaction between dicarboxylic acid ester and glycol, polycondensation reaction of dicarboxylic acid ester, metathesis reaction between dicarboxylic acid chloride and diol, etc. It can be manufactured by 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 long-chain diol compound with a molecular weight of 500 or more are combined in the presence of a catalyst. Approximately 150 mL under an inert gas atmosphere such as nitrogen gas
This is done by heating 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 approximately 1 mmHg or less and at a temperature range from the melting point of the resulting copolymer to 300°C. The melting point of the copolymer is preferably in the range of 260°C. Also,
Also in this polycondensation reaction step, a compound such as lead, titanium, antimony, niobium, germanium or the like may be added as a catalyst, if necessary. The reduction ratio clay (η _sp /C) of the polyester elastomer of the present invention thus obtained is 0.5 to 3.0 (mixture of phenol/tetrachloroethane = 1/1 (volume ratio)) from the viewpoint of practical strength. (Measured using a solvent, polymer concentration C=0.5g/dl, 25℃)
It is preferably 0.7 to 2.0, and more preferably 0.7 to 2.0. The polyester elastomer produced in this way can be used in medical devices that come into contact with blood or biological soft tissue, such as blood circuits, blood bags, etc., by extrusion molding, injection molding, or coating methods.
It can be suitably used for applications such as catheters, blood pumps, blood transfusion sets, housings for various artificial organs, artificial blood vessels, and sutures. The present invention will be explained below using Examples. Note that "parts" in Examples and Comparative Examples mean parts by weight, and the reduction ratio clay (η _sp /C) uses a mixed solvent of phenol/tetrachloroethane = 1/1 (volume ratio), and the polymer concentration C = 0.5g/dl,
This is a value measured at 25℃. 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) was added to an autoclave at a jacket temperature of 160° C. under a nitrogen gas atmosphere and stirred. It takes 100 minutes to raise the temperature to 250℃ under normal pressure, and when the transesterification reaction is completed, 62 parts of polytetramethylene glycol with a molecular weight of 2000 and polydimethylsiloxane with polyethylene glycol at both ends (molecular weight about 2400, polydimethylsiloxane) are combined. 1080 and 13 parts of polyethylene glycol, each having a molecular weight of approximately 660, were added, and the pressure in the system was gradually reduced to remove methanol and 1,4-butanediol. The temperature was reduced to 0.5 mmHg or less, and polycondensation was continued for 100 minutes to obtain a polyester elastomer. The reduced specific viscosity of this elastomer was 1.2.
A JIS No. 3 dumbbell type test piece was prepared and the tensile strength measured using Shimadzu Autograph IS-2000 was 320Kg/
cm ² , the elongation was 710%. Next, the interaction of this elastomer with blood was measured by the following method. That is, producing a sheet of the elastomer,
It was cut into squares of 3 cm x 3 cm and placed on a watch glass with a lid maintained at 37°C. Add dog ACD blood (soda citrate,
After placing a certain amount of a holding plate made non-coagulable by adding glucose, etc., an aqueous calcium chloride solution is added, and the amount of clotted blood (thrombus) is measured at predetermined intervals. Thrombus formation rate (%) = The weight of the thrombus formed on the sheet after a certain period of time/the weight of the final thrombus formed on the glass x 100 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, 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.

[Table] 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 a molecular weight of 1025, (average molecular weight 1030) 75 parts, tetra-n-butyl titanate 1.5 parts, antioxidant (Irganox
1010 (manufactured by Ciba Geigy) was added to an autoclave at a jacket temperature of 200°C under a nitrogen gas atmosphere and stirred. The temperature was raised to 250°C over 100 minutes at normal pressure, and methanol was distilled off. After reaching 250℃, gradually reduce the pressure to 0.5mmHg for 30 minutes.
Polycondensation was carried out as follows. A polyester elastomer was obtained by carrying out a polycondensation reaction for 100 minutes. The reduction ratio clay of this elastomer was 1.0.
A JIS No. 3 Bendal type test piece was prepared and the tensile strength measured using Shimadzu Autograph IS-2000 was 400Kg/
cm ² , the 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 3-4 From the composition of Example 2 (average molecular weight 1030), the molar amount corresponding to this molar amount polytetramethylene glycol (molecular weight
A polyester elastomer was produced under the same conditions as in Example 1, except that the amount of 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.

[Table] Example 3 In Example 2, instead of polytetramethylene glycol with a molecular weight of 1025, the same number of moles of polytetramethylene glycol with a molecular weight of 1000 was used. When used, a polyester elastomer with a reduced specific viscosity of 0.95 was obtained. Example 4 When the same number of moles of ethylene glycol was used in place of 1,4-butanediol in Example 3, 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 the sheet etc. made of the polyester elastomer of the present invention comes into contact with blood or biological soft tissue,
It has little interaction with these substances and exhibits excellent antithrombotic properties. This property is due to the microphase separation structure in which the soft segment becomes a hydrophobic domain and the hard segment becomes a hydrophilic domain, and because a part of the soft segment contains an organosilicon polymer moiety, it is possible to mutually interact with living tissues. This is presumed to be due to the formation of a microphase-separated structure with low effectiveness. 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 suitably used for medical devices that come into contact with blood or biological soft tissue, such as blood circuits, blood bags, catheters, blood pumps, blood transfusion sets, housings for various artificial organs, artificial blood vessels, sutures, etc. It can be done.

Claims (1)

[Claims] 1. As a soft segment, general formula (1): (In the formula, R ₁ and R ₂ are 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 an organosilicon polymer moiety having a molecular weight of 200 to 10,000, which is a group obtained by fluorinating these groups, where R ₁ and R ₂ may be the same or different, and n is an integer of 1 or more. General formula (2) containing: X-A-Y (2) (wherein A is an organosilicon polymer moiety, X and Y are -
(R ₇ ) _f -(OR ₈ ) _g -OH (R ₇ and R ₈ are alkylene groups having 2 or more carbon atoms, f is 0 or 1, and g is an integer from 0 to 30), and the same and polyethylene glycol, polypropylene glycol, polytetramethylene glycol, a glycol consisting of a block polymer thereof, or general formula (3): (In the formula, R is an alkylene group having 2 to 6 carbon atoms, and h is an integer of 1 or more).
A polyester elastomer containing the following diol compound portion and dicarboxylic acid compound portion, wherein the proportion of the organosilicon polymer portion contained in the elastomer is 1 to 50% by weight. 2 General formula (1): (In the formula, R ₁ and R ₂ are 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 an organosilicon polymer moiety having a molecular weight of 200 to 10,000, which is a group obtained by fluorinating these groups, where R ₁ and R ₂ may be the same or different, and n is an integer of 1 or more. General formula (2) containing: X-A-Y (2) (wherein A is an organosilicon polymer moiety, X and Y are -
(R ₇ ) _f -(OR ₈ ) _g -OH (R ₇ and R ₈ are alkylene groups having 2 or more carbon atoms, f is 0 or 1, and g is an integer from 0 to 30), and the same diol compounds represented by (may be or may be different), polyethylene glycol, polypropylene glycol, polytetramethylene glycol with a molecular weight of 500 or more, glycols consisting of block polymers thereof, or general formula (3): (In the formula, R is an alkylene group having 2 to 6 carbon atoms, h is an integer of 1 or more) A polyester elastomer made by reacting a polyether long chain diol compound, a diol compound with a molecular weight of 300 or less, and a dicarboxylic acid compound moiety. 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.