KR100458734B1 - Medical Device - Google Patents

Abstract

The present invention provides a solution having an elongated shaft formed from a thermoplastic elastomer material selected from the group consisting of polyether block amide and styrene block copolymer, containing 0.05 to 40% (w / v) of isocyanate compound and Passage of the body comprising applying a solution containing 0.5 to 50% (w / v) polyvinylpyrrolidone to the surface of the elongated shaft in order and curing at elevated temperature to form a hydrophilic coating on the elongated shaft A method of making a medical device having a hydrophilic surface coated elongated shaft for insertion into a furnace.

Description

Medical Device {Medical Device}

FIELD OF THE INVENTION The present invention relates to medical instruments having elongated shafts coated with outer surfaces for insertion into the passages of a human or animal body, and in particular but not limited to surface coated catheters.

Many medical instruments include elongated shafts, such as tubes, designed for insertion into the passage of a living body, such as those of the urethra and cardiovascular system. The most common form of holistic integration of such medical devices is known as catheter. Examples of catheters are those designed for use in urinary, angioplasty and valve surgery, that is, living bodies, generally adapted for insertion into the urethra, vascular cavity and cardiac passages of the human body, respectively.

Due to the intended use of the medical device, the material used to make the elongated shaft must meet certain requirements. This material must meet requirements such as ductility, good kink suppression, good dimensional stability, processability (e.g., easy to form and adhere to), and sterilization by radiation, steam, ethylene oxide or other means. do. The material also needs to be subjected to a surface treatment that imparts the desired surface properties such as lubricity, hydrophilicity and blood compatibility to the medical device. For the purpose described at the end, the chemistry of the base material is important because it affects the coating properties of the base material.

Because polyvinyl chloride (PVC) meets the requirements mentioned in the preceding paragraph, PVC has been used in recent years for the manufacture of medical devices with elongated shafts for insertion of body passages, such as catheters.

For example, conventional European Patent Application Publication No. 0093093 (Astra Meditec ABS) describes a method of making a hydrophilic coated PVC urethral catheter with an outer surface that exhibits a low coefficient of friction when wet. This method involves a solution containing 0.05-40% (weight / volume, ie kg / l) of isocyanate compound and a solution containing 0.5-50% (weight / volume) of polyvinylpyrrolidone (PVP) of the catheter. Applying (eg, immersing) to the outer surface in order, and then advantageously curing the hydrophilic coating at elevated temperature in the presence of a water-containing gas such as air to form a hydrophilic surface coating on the PVC catheter.

However, the suitability of PVC for medical devices such as catheters is currently questioned due to environmental reasons and also the toxicity of plasticizers added to PVC. Moreover, the coating of PVC catheter, for example by the method of European Patent Application Publication No. 0093093, causes the PVC to shrink significantly (usually 6-7% of its original length) in the longitudinal direction, due to the operating temperature used in this process. The obvious disadvantage of this significant shrinkage is the waste of the material due to the fact that PVC catheter must be used which is longer than the length finally needed in view of the shrinkage. In addition, the quality control of the coating process will be more complicated than one thinks due to this marked shrinkage.

Therefore, there is a need for medical instruments with elongated shafts of hydrophilic surface coated non-PVC for insertion into the body passages, where significant shrinkage does not occur upon application of the hydrophilic surface coating.

To this end, the present invention provides the steps of forming an elongated shaft from a thermoplastic elastomer material selected from the group consisting of polyether block amides and styrene block copolymers, and solutions containing 0.05 to 40% (weight / volume) of isocyanate compounds and Applying a solution containing 0.5 to 50% (weight / volume) of polyvinylpyrrolidone to the surface of the elongated shaft sequentially and curing at elevated temperature to form a hydrophilic coating on the elongated shaft. A method of making a medical instrument with a long, elongated shaft coated with a hydrophilic surface for insertion is provided.

The use of polyether block amides or styrene block copolymers provides an elongated shaft that has virtually no longitudinal shrinkage and has the general properties necessary for insertion into the body passages as compared to PVC in the application of hydrophilic coatings. Therefore, the present invention, which in particular leads to a small waste of starting material, can provide a catheter that compensates for the disadvantages of the PVC based catheter described above and can use a TV monitor for quality control.

The background portion of conventional European patent application publication 0566755 (Cordis Corp.) is known per se that the use of polyether block amides for making medical instrument tubes designed for insertion into body passages. On the other hand, European Patent Application Publication No. 0566755 discloses that, after prolonged storage, undesired blooming may occur on the tube material, such as a coating for imparting lubricity to the tube. It teaches that it happens. The solution to the blooming problem according to European Patent Application Publication No. 0566755 is to mix the polyetheramide with a polyetheramide component which is substantially free of ester bonds.

Despite the fact that sometimes blooming is observed after several months of storage, it is evident that according to the method according to the invention there is no such problem due to the application of a hydrophilic coating to the polyether block amide. This may be due to the way in which the hydrophilic coating is applied to the elongated shaft by the method according to the invention.

The polyether block amide used in the present invention has the following formula.

Wherein PA is polyamide,

PE is polyether,

n represents the number of block copolymer molecular repeating units in the molecular formula of a copolymer, and is an integer greater than one. Representative polyether block amide materials include Pebax® Elf Atochem S.A. polymers.

In an embodiment of the invention, the styrene block copolymer is a styrene-ethylene / butylene-styrene block copolymer, such as Evoprene G (Evode Plastics Ltd.).

Application of an isocyanate solution to the surface of the elongated shaft forms a coating with unreacted isocyanate groups on the surface of the elongated shaft. Application of the polyvinylpyrrolidone solution to the elongated shaft surface forms a hydrophilic polyvinylpyrrolidone-polyurea copolymer coating on the elongated shaft surface. Curing this hydrophilic coating binds together with the isocyanate compound to form a stable non-reactive network that binds the hydrophilic polyvinylpyrrolidone. Advantageously, curing is carried out in the presence of a water-containing gas such as air to cause isocyanate groups to react with water, resulting in amines that react rapidly with other isocyanate groups to form urea crosslinks.

In an aspect of the invention, the method also includes evaporating the solvent of the isocyanate solution before applying the polyvinylpyrrolidone solution and evaporating the solvent of the polyvinylpyrrolidone solution before curing the hydrophilic coating. . This can be done by air drying.

In an embodiment of the invention, the isocyanate compound comprises at least two unreacted isocyanate groups per molecule. Isocyanates are pentamers of 2,4-toluene diisocyanate and 4,4'-diphenylmethane diisocyanate, or toluene diisocyanate of hexamethylene diisocyanate and cyanurate type, or trimerized hexamethylene diisocyanate burette or May be selected from mixtures thereof.

It is preferred that the solvent for the isocyanate compound does not react with the isocyanate group. Preferred solvents are methylene chloride, but it is also possible to use, for example, ethyl acetate, acetone, chloroform, methyl ethyl ketone and ethylene dichloride.

The isocyanate solution is advantageously containing between 0.5 and 10% (weight / volume) of the isocyanate compound, and may preferably contain 1 to 6% (weight / volume) of the isocyanate compound. In general, the isocyanate solution only needs to contact the surface for a short time of 5 to 60 seconds.

In order to increase the adhesion of the hydrophilic coating to the elongated shaft surface, the elongated shaft may be previously wetted with a suitable solvent. Another method is to select a solvent for the isocyanate solution that can wet or dissolve the elongated shaft surface to be coated.

In order to shorten the necessary reaction time and curing time, a catalyst suitable for isocyanate curing may be added. These catalysts can be dissolved in either isocyanate solution or polyvinylpyrrolidone solution, but are preferably dissolved in the latter. Different forms of amines are particularly useful, for example diamines and triethylenediamines. Preference is given to using aliphatic amines which are volatile at the drying and curing temperatures used in the coating and, moreover, nontoxic. Examples of suitable amines are N, N'-diethylethylenediamine, hexamethylenediamine, ethylenediamine, paradiaminobenzene, 1,3-propanediol-para-aminobenzoic acid diester and diaminobicyclo-octane.

If the catalyst is in a polyvinylpyrrolidone solution, the proportion of catalyst in the solution is suitably 0.1 to 50% by weight, preferably 0.1 to 10% by weight, based on the amount of polyvinylpyrrolidone. Some of these amines, especially diamines, can also react with isocyanates, contributing to the crosslinking of isocyanate compounds, which imparts the desired strong adhesion between the hydrophilic coating and the polymer surface.

The average molecular weight of the polyvinylpyrrolidone used is preferably 10 ⁴ to 10 ⁷ , most preferably about 10 ⁵ . Polyvinylpyrrolidone having this molecular weight is commercially available, an example of which is Kollidon (registered trademark, BASF). Suitable solvents for the polyvinylpyrrolidone that may be used are methylene chloride (preferably), ethyl acetate, acetone, chloroform, methyl ethyl ketone and ethylene dichloride. The proportion of polyvinylpyrrolidone in the solution is preferably 0.5 to 10% (weight / volume), most preferably 2 to 8% (weight / volume). Polyvinylpyrrolidone in the solvent is applied, for example, by dipping, spraying or the like for a short time of 5 to 50 seconds.

Curing of the coating is preferably carried out at a temperature of 50 to 130 ° C., for example in an oven for 5 to 300 minutes.

According to the invention, there is also provided a medical device in which there is a hydrophilic surface coated elongated shaft for insertion into a body passage made by the method of the invention.

According to the invention, there is also an elongated shaft for insertion into the body passages, which is made of polyether block amide or styrene block copolymers and is provided with a hydrophilic outer coating formed from a mutually permeable network of polyvinylpyrrolidone and polyurea. Provide a medical instrument that exists.

According to the present invention, a medical device having an elongated shaft for insertion into the body passages, which is made of polyether block amide or styrene block copolymer and is provided with a polyvinylpyrrolidone hydrophilic outer coating having increased osmolality To provide.

In an embodiment of the invention, the hydrophilic coating contains an osmolality-increasing compound, for example, an inorganic salt selected from sodium chloride, potassium chloride, sodium iodide, potassium iodide, sodium citrate, potassium citrate, sodium benzoate and potassium benzoate. Osmolality-increasing compounds can be used in the manner described in detail in the prior European Patent Application Publication No. 0217771.

In an aspect of the present invention, the medical device is a catheter, for example designated for urinary, angioplasty and valve surgery use and the like. In this case, the polyether block amide or styrene block copolymer selected for the elongate shaft has hardness in the range of 25 Sh D to 70 Sh D and 40 shore A to 70 Shore D, respectively. When the medical device is a urethral catheter, the hardness of the polyether block amide and styrene block copolymer is ideally 25 Sh D to 45 Sh D and 40 Shore A to 45 Shore D, respectively, which is greater than the hardness desired for intravenous catheter.

Also in accordance with the present invention, there is provided the use of styrene block copolymers in the manufacture of medical devices in which there is an elongated shaft for insertion into the body pathway.

The invention is illustrated by, but not limited to, the following examples.

<Example 1>

Diisocyanate (called Desmodur IL) was dissolved in methylene chloride at a concentration of 2% (weight / volume). A urethral catheter (hereafter referred to as 'urethral pebox catheter') formed solely or essentially of a pebox with a hardness of 70 Shore D (hereinafter referred to as 'urethral pebox catheter') was dipped in the solution for 15 seconds and then dried at ambient temperature for 60 seconds. This catheter was then immersed in methylene chloride for 1 second in a solution of polyvinylpyrrolidone (K90; average molecular weight ˜360,000) at 6% (weight / volume). The catheter was then left to dry at ambient temperature for 60 seconds and finally cured at 100 ° C. for 50 minutes. Finally, the catheter was allowed to cool to room temperature and then rinsed with water. The surface of the catheter was smooth and sticky in the wet state.

This experiment was repeated with various immersion times in an isocyanate bath in the range of 5 seconds to 1 minute, but there was no benefit from increasing the immersion time.

<Example 2>

Diisocyanate (called Desmodur IL) was dissolved in ethyl acetate at a concentration of 2% (weight / volume). A urethral pebox catheter of 35 Shore D hardness was immersed in this solution for 15 seconds and then dried at ambient temperature for 60 seconds. It was then immersed in a solution in which polyvinylpyrrolidone (K90; average molecular weight ˜360,000) in 6% (weight / volume) dissolved in ethyl lactate (50%) and ethyl acetate (50%) for 1 second. The catheter was then left to dry at ambient temperature for 60 seconds and finally cured at 80 ° C. for 50 minutes. Finally, the catheter was allowed to cool to room temperature and then rinsed with water. The surface of the catheter was smooth and sticky when wet.

<Example 3>

Diisocyanate (called Desmodur IL) was dissolved in methylene chloride (75%) and trichloro ethylene (25%) at a concentration of 2% (weight / volume). A urethral pebox catheter of 63 Shore D hardness was immersed in this solution for 15 seconds and then dried at ambient temperature for 60 seconds. The catheter was then immersed in a solution in which polyvinylpyrrolidone (K90; average molecular weight ˜360,000) was dissolved in 6% (weight / volume) in methylene chloride (75%) and trichloroethylene (25%) for 1 second. The catheter was then left to dry at ambient temperature for 60 seconds and finally cured at 100 ° C. for 50 minutes. Finally, the catheter was allowed to cool to room temperature and then rinsed with water. The surface of the catheter was smooth and sticky when wet.

<Example 4>

Diisocyanate (called Desmodur IL) was dissolved in ethyl acetate at a concentration of 2% (weight / volume). A urethral catheter made from Evoprene G with a hardness of 65 Shore A was immersed in this solution for 15 seconds and then dried at ambient temperature for 60 seconds. The catheter was then immersed in a solution in which polyvinylpyrrolidone (K90; average molecular weight ˜360,000) dissolved in methylene chloride at 6% (weight / volume) for 1 second. The catheter was then left to dry at ambient temperature for 60 seconds and finally cured at 100 ° C. for 50 minutes. Finally, the catheter was allowed to cool to room temperature and then rinsed with water. The surface of the catheter was smooth and sticky when wet.

Urethral catheters prepared according to the examples show low friction, good kink suppression, good dimensional stability and sterilization. Moreover, the longitudinal shrinkage of the catheter as a result of the coating process was less than 1% of the original length.

Although the embodiments relate to the manufacture of a urethral catheter, the present invention is not limited to this one use but is a medical instrument (eg, erectile) having a different type of catheter and moreover an elongated shaft suitable for insertion into the body passage as a whole. It should be understood that the same can be used for other structures within the broad field of disinfecting urinary instruments and wound drains for insertion of body passages in the form of wound cavity.

Claims (22)

Forming an elongated shaft from a thermoplastic elastomer material selected from the group consisting of polyether block amides and styrene block copolymers, and solutions containing 0.05 to 40% (w / v) isocyanate compounds and polyvinyl Inserting a solution containing 0.5 to 50% (w / v) of pyrrolidone into the surface of the elongated shaft in order and curing at elevated temperature to form a hydrophilic coating on the elongated shaft; A method of making a medical instrument having a hydrophilic surface coated elongated shaft for the purpose of. The method of claim 1 wherein the isocyanate compound contains at least two unreacted isocyanate groups per molecule. The method according to claim 1 or 2, wherein the solvent of the isocyanate solution is an organic solvent which does not react with the isocyanate. The method of claim 1 or 2, further comprising evaporating the solvent of the isocyanate solution prior to application of the polyvinylpyrrolidone solution, and evaporating the solvent of the polyvinylpyrrolidone solution prior to curing. How to. The process according to claim 1 or 2, wherein the curing is carried out in the presence of a water-containing gas. The process of claim 1 or 2, wherein the curing is performed at a temperature of about 50 to 130 ° C. The process according to claim 1 or 2, wherein the styrene block copolymer is a styrene-ethylene / butylene-styrene block copolymer. The process according to claim 1 or 2, wherein the polyether block amide selected for the elongate shaft has a hardness in the range of 25 Sh D to 70 Sh D. 8. The method of claim 7, wherein the styrene-ethylene / butylene-styrene block copolymer selected for the elongated shaft has a hardness in the range of 40 Sh A to 70 Sh D. The pentameric according to claim 1 or 2, wherein the isocyanate is 2,4-toluene diisocyanate, 4,4'-diphenylmethane diisocyanate, or hexamethylene diisocyanate and toluene diisocyanate of cyanurate type, Or trimerized hexamethylene diisocyanate biuret or mixtures thereof. The method of claim 1 or 2, comprising using a solution containing an osmolality-increasing compound for the hydrophilic coating, and evaporating a solution containing the osmolality-increasing compound. How to. The method of claim 11, wherein the osmolality-increasing compound is an inorganic salt selected from sodium chloride, potassium chloride, sodium iodide, potassium iodide, sodium citrate, potassium citrate, sodium benzoate and potassium benzoate. A medical device having a hydrophilic surface coated elongated shaft for insertion into a body passage made by the method according to any one of claims 1 to 12. A medical device having an elongated shaft for insertion into a body passage, characterized by being provided from a polyether block amide or styrene block copolymer and provided with a hydrophilic outer coating formed from a mutually permeable network of polyvinylpyrrolidone and polyurea. A medical device having an elongated shaft for insertion into a body passage, which is made from a polyether block amide or styrene block copolymer and is provided with a polyvinylpyrrolidone hydrophilic outer coating having an increased osmolality. The medical device according to claim 14 or 15, wherein the styrene block copolymer is a styrene-ethylene / butylene-styrene block copolymer. The medical instrument of claim 14 or 15, wherein the elongated shaft is formed from a polyether block amide having a hardness in the range of 25 Sh D to 70 Sh D. 17. The medical device of claim 16, wherein the elongated shaft is formed from styrene-ethylene / butylene styrene block copolymer having a hardness in the range of 40 Sh A to 70 Sh D. The medical device of claim 14 or 15, wherein the hydrophilic coating contains an osmolality-increasing compound. 20. The medical device of claim 19, wherein the osmolality-increasing compound is an inorganic salt selected from sodium chloride, potassium chloride, sodium iodide, potassium iodide, sodium citrate, potassium citrate, sodium benzoate and potassium benzoate. The medical instrument of claim 14 or 15, which is a catheter. The medical instrument of claim 21, which is a urethral catheter.