NL8204162A - EXTRUSIBLE POLYURETHANE FOR PROSTHETIC INSTRUMENTS. - Google Patents

Description

N / 31.177 / Kp / Pf / vdM 1 - * y - 1 -

Extrudable polyurethane for prosthetic instruments.

The invention relates to a highly blood-compatible polymer for use in molding devices.

Significant progress has been made in recent years in the development of vascular prostheses. For example, U.S. Patent 4,131,604 describes a group of polyurethanes with excellent properties that can be used for the manufacture of moldable prosthetic instruments. However, the polyurethane described in said patent falls short because it is not extrudable. There are many prosthetic devices, as well as other types of devices that must be compatible with blood, which can only be efficiently manufactured by extrusion or blow molding.

Of course, instruments such as pacemaker leads, blood bags, catheters, and IV tubes must be made of a material that meets a number of requirements.

Most importantly, the fact that the material from which such instruments are made is compatible with blood. I.e. the material should not induce the formation of a thrombus, which can obstruct peripheral blood flow. Furthermore, the material must of course not be toxic. In addition, it is desirable that instrument materials used in the manufacture of vascular prostheses have high resilience, strength, and an ability to bend without breaking. As already mentioned above, it is moreover desirable for the formation of certain instruments that the material is extrudable.

The present invention relates to a group of extrudable polyurethane polymers, which have been especially developed for use in instruments that are highly compatible with bleed.

Accordingly, according to the invention, the polymer as described in the preamble is characterized in that it is a polyurethane elastomer obtained as a reaction product of: a. A diisocyanate selected from the group 820 4 1 52 4 - 2 - consisting of isophorone diisocyanate, trimethylhexamethylene diisocyanate, dicyclohexylmethane diisocyanate and dimer acid diisocyanate, b. a polytetramethylene ether polyol having a molecular weight in the range of 500-5000; and c. 1,4-butanediο1.

The polymers of the invention are essentially linear, segmented, aliphatic polyurethane elastomers. This group of polymers, which are aliphatic and poly-ether based with 100% urethane bonds in the molecular backbone, exhibit superior flexibility of life, excellent hydrolytic stability and a high degree of blood compatibility. In addition, the polymers can be granulated and extruded into instruments of various shapes, such as cardiac pacemaker leads, blood bags, catheters and IV tubes. This unusual combination of properties makes this group of polymers useful in devices exhibiting surfaces that come in contact with blood.

The polyurethane elastomer of the present invention is a rubbery reaction product of aliphatic organic diisocyanates, high molecular weight polyether polyols and a certain low molecular weight glycol (chain extender). This low molecular weight glycol is 1.4-25 butanediol.

In addition to the above-mentioned necessary constituents, it is also preferred to use a catalyst and, if necessary. an antioxidant and a lubricant for extrusion purposes.

In general, polyurethane polymers are the condensation product of reactions between diisocyanates and compounds containing active hydrogen atoms, such as hydroxyl groups.

A diisocyanate is an isocyanate compound with a functionality of two. The polymerization takes place in the presence of a difunctional hydroxyl compound (this can be either a simple glycol or a macromolecular glycol).

820 4 1 62

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- 3 -. ... cat.alys.ator n Ob = sC == N — R — N == C = 0 + HO · —R —OH ...... ......— n ---> ( diisocyanate) (glycol) -C (= 0) -NH-R-NH-C (= 0) -OR ^ O- (polyurethane)

Examples of aliphatic diisocyanates which can be used according to the invention are: hexamethylene diisocyanate (HDI), OCN (CH2) gNCO; isophorone diisocyanate (IPDI), formula 1; trimethylhexamethylene diisocyanate (TMHDI), formula 2; dicyclohexylmethane diisocyanate (HMDI), formula 103; and dimer acid diisocyanate (DDI), formula 4.

Dicyclohexylmethane diisocyanate (HMDI) is the preferred diisocyanate for forming polymers according to the invention.

Although various aliphatic diisocyanates can be used for the preparation of a polymer according to the present invention, numerous experiments have shown that the selection of the high molecular weight polyol is limited to polytetramethylene ether glycol (PTMEG), 20 H— (0-CH2— CH2 — CH2 — CH2) n — Said, this high molecular weight polyol is the only polyol found to yield a polyurethane that is compatible with blood and also has the other properties discussed above. Generally, this glycol should have an average molecular weight between 500 and 5000, preferably between 1000 and 3000. In a preferred embodiment of the invention, PTMEG having a molecular weight of 20Q0 has been used.

As already mentioned, the polymer chain extender of the present invention is 1,4-butanediol (HO-CH2-CH2-CH2-CH2-OH).

Accordingly, the preferred polyurethane according to the invention has a structure according to formula 5 of the formula sheet, wherein n ^ is an integer chosen such that a molecular weight of the macroglycol 35 is obtained between 500 and 5000, x a integer is from 8204162-4-1-5 and n is an integer chosen to give a molecular weight of the order of 315,000.

As can be seen from formula 5, the polymer of the present invention consists of three repeating units, the diol, the diisocyanate and the macroglycol. The ratio between these repeating units is determined by the desired physical properties. For example, for tubes, which should be soft and elastomer (70 Shore A), there are two diisocyanate units and macroglycol for each diol. To obtain harder material, the ratio of diol to diisocyanate and. macroglycol are increased, yielding a harder material. For example, for catheters (50 Shore D), two butanediol units are repeated per each isocyanate and each macroglycol.

The reagents are collected in approximately the molar amounts necessary to obtain the said polymer.

In order to obtain fully cured polyurethane castings in a reasonably short period of time, it is usual to include a suitable catalyst in the mixture to promote the polymerization reaction. Suitable catalysts are N-methylmorpholine, trimethylamine, triethylamine, zinc octoate, dibutyltin dilaurate and dioctyltin dilaurate. Dioctyltin dilaurate is the preferred catalyst.

The method according to the present invention is schematically shown in the accompanying drawing.

The polyurethane is prepared from two components, designated Part A and Part B. Part A is the aliphatic diisocyanate. Part B includes the other ingredients: a macroglycol (the polyether base), the low molecular weight chain extender, the catalyst, the antioxidant and the lubricant. Of course, the catalyst, antioxidant and lubricant are not chemically part of the polymer.

For the formation of a polyurethane element, the appropriate stoichiometric proportions of Part A and Part B are emulsified at room temperature by means of a mixer to form a moderately reactive thixotropic 8204162 * - 5 mixture with a viscosity below about 2. , 5 Pa.s.

Since air is introduced into the reaction mixture by the emulsification, this air must be removed. The air bubbles are removed by placing a vessel containing the emulsion 5 under a bell jar and exhausting the air from the bell jar by means of a suction device. evacuate. The bell is evacuated to a pressure of about 0.3 microns and the mixture is kept under the bell for about 8 minutes, whereby the mixture appears to be boiling. After the emulsion has been removed from under the bell jar, it is left to stand until the exothermic reaction that takes place has brought it to a temperature of about 400 ° C.

At that time, the emulsion is preferably poured into a pan into which the emulsion flows, forming uncured sheets. The sheet pan is then placed on the fire and heated at a temperature of at least 110 ° C for 4 h or more until the elastomer has cured. The sheets are then cut or granulated in a normal granulator, yielding granules about 6.4 mm in length. These granules are then used in equipment suitable for extrusion to the desired product.

According to an alternative embodiment of the invention, it is also possible to dissolve the granules in a solvent, such as dimethylacetamide, tetrahydrofuran, 1,4-dioxane or m-pyrrole. The solution can then be used to make an article by the solvent casting method.

The invention is now further elucidated by means of the following non-limiting example.

30 EXAMPLE.

Dicyclohexylmethane diisocyanate (HMDI) in an amount of 67.75 g was reacted with the mixture of the following five components: 229.2 g of 2000 molecular weight polytetramethylene ether glycol, and 12.35 g of 1,4-butanediol. This reaction mixture also contained 3.0 g of antioxidant. The antioxidant used is available under the brand name IRGANOX 1010 from Ciba-Geigy. The chemical name of this antioxidant is tetrakis / methylene (3,5-di-tert-butyl-4-8204162-6-hydroxyhydrocinnamate) 7 methane. Also contained in this reaction mixture was 0/5 g of lubricant, which is available under the brand name GLYCOLUBE VL from Glyco Chemical Company of New York, USA Finally, 0.006 g of a tin-based catalyst was also available, which is available under the trade name COTIN 430 from Cosan Chemical Corporation of Carlstadt, New Jersey, U.S.A.

The above components were mixed with the HMDI, vented until all trapped gases were out

10 removed. The mixture was then placed at 110 ° C for 3 h

cured in the form of sheets under a nitrogen atmosphere.

The sheets were then cut into pieces in a standard pelletizer to form pellets suitable for extrusion. The physical properties of the cured elastomer were as follows: tensile strength 315 kg / cm, elongation 650%, hardness (Shore A) 70-75.

The granules were then processed in a laboratory extruder. The processing conditions of the used 24/1 screw with a diameter of 25 mm, were 20 as follows:

behind; 149 ° C

middle: 160 ° C

for: 160 ° C

mold: 166 ° C

25 neck: water cooling.

Tubing with dimensions suitable for use as pacemaker leads has been extruded. The hoses exhibited all the desired physical properties required for the desired application.

30 820 4 1 62

Claims (5)

1. A highly blood-compatible polymer for use in molding devices, characterized in that the polymer is a polyurethane elastomer and is obtained as a reaction product of; a. A diisocyanate selected from the group consisting of isophorone diisocyanate, trimethylhexamethylene diisocyanate, dicyclohexylmethane diisocyanate and dimer acid diisocyanate; 10 b. a polytetramethylene ether polyol with a molecular weight in the range of 500-5000; and c. 1,4-butanediol. 2. A polymer according to claim 1, characterized in that the diisocyanate is dicyclohexylmethanediiso-cyanate. 3. Polymer according to claim 2, characterized in that the polymer is dissolved in a solvent. 4. Polymer according to claim 2, characterized in that the polymer is in the form of granules. Two-component system for forming a polyurethane elastomer, characterized in that the system comprises as first component a) dicyclohexylmethane diisocyanate and as second component b) a stoichiometric amount of polytetramethylene ether polyol and 1,4-butanediol. 30 8204162