KR101740304B1

KR101740304B1 - Medical catheter comprising hydrophilic oxidized polysaccharide coating layer and manufacturing method thereof

Info

Publication number: KR101740304B1
Application number: KR1020150088805A
Authority: KR
Inventors: 이영우; 임소연
Original assignee: (주)헵틸와이
Priority date: 2015-06-23
Filing date: 2015-06-23
Publication date: 2017-05-29
Also published as: KR20170000081A

Abstract

TECHNICAL FIELD The present invention relates to a technique for improving the hydrophilicity of a medical catheter by coating an oxidized polysaccharide oxidized with an oxidizing agent on the surface of a medical catheter, thereby greatly increasing lubrication upon insertion into a human body.
The medical catheter comprising the hydrophilic oxidized polysaccharide coating layer prepared according to the present invention has excellent biocompatibility and the lubricity is greatly increased upon insertion into the human body, so that it is not necessary to process the pre-insertion lubricant, and the side effects such as arterial puncture and vessel separation It can be applied to various medical conduits including catheters as well as blood vessels.

Description

TECHNICAL FIELD The present invention relates to a medical catheter comprising a hydrophilic oxidizing polysaccharide coating layer and a manufacturing method thereof,

The present invention relates to a medical catheter comprising a hydrophilic oxidizing polysaccharide coating layer and a method of manufacturing the same, and more particularly, to a medical catheter having a hydrophilic oxidizing polysaccharide oxidized by using an oxidizing agent, The present invention relates to a technique for largely increasing the lubricity at the time of use.

In general, a catheter is a thin tube formed by extrusion molding using a medical material, and is generally referred to as a catheter inserted into a human body for the purpose of treating a disease or performing surgery. That is, since the catheter is applied to a variety of clinical fields such as cardiovascular, urinary and digestive machines, it is inserted into a human body such as steel, a tube, and a blood vessel. Particularly, in order to diagnose or treat ischemic cardiovascular diseases such as arteriosclerosis and angina pectoris, a guiding catheter and a balloon catheter are inserted through the femoral or wrist aorta into the narrowed blood vessel region, and then the balloon is inflated to expand the coronary artery Percutaneous transluminal coronary angioplasty.

However, most of the catheters used in intracorporeal catheterization including percutaneous coronary angioplasty are hydrophobic polymers such as polyethylene, polytetrafluoroethylene, polyamide, polyurethane, silicone, etc., Because the lubrication is poor, it is inconvenient to apply lubricant to the catheter prior to the procedure. In the procedure of introducing the catheter, such as the catheter through the aorta, the arterial restenosis occurs in 30 ~ 40% Side effects such as perforation or vascular dissociation have been reported.

Therefore, in order to solve the above-mentioned side effects, there has been proposed a method of securing lubricity by performing a hydrophilic coating having a low wettability coefficient on the surface of a medical catheter to smoothly slide the catheter during insertion. , There was still room for improvement in improvement of biocompatibility and reduction of wettability coefficient (Patent Documents 1 to 3).

Therefore, the present inventor has solved the problem caused by the use of the conventional medical catheter, and at the same time, there has been no example of forming a coating layer based on an oxidizing polysaccharide system on the catheter. When the surface of a conventional medical catheter is coated with an oxidizing polysaccharide, And thus the lubricity can be greatly increased upon insertion into the human body. Thus, the present invention has been accomplished.

Patent Document 1 International Patent Publication No. WO 98/058990 Patent Document 2: Korean Patent Publication No. 10-1124599 Patent Literature 3 US Patent Publication No. US 2014/0249489

SUMMARY OF THE INVENTION The present invention has been made in view of the above problems, and it is an object of the present invention to provide a method and apparatus for osteoarthritis which are excellent in biocompatibility, And a hydrophilic oxidizing polysaccharide coating layer which does not cause side effects such as inflammation and the like, and a method of manufacturing the medical catheter.

In order to achieve the above object, the present invention provides a medical catheter, wherein the surface of the catheter is coated with a hydrophilic oxidizing polysaccharide.

The oxidized polysaccharide may be selected from the group consisting of oxidized carboxymethylcellulose, carboxyethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, dextrin, dextran, dextran sulfate, alginic acid, hyaluronic acid, chitin, chitosan, gellan gum, glucan, And at least one selected from the group consisting of chondroitin sulfate, glycogen, starch, cellulose, regenerated cellulose, maltodextrin, fructan, galactan and mannan.

The oxidized polysaccharide is characterized in that the molecular weight of the polysaccharide before oxidation is 1,000 to 100,000.

The oxidation polysaccharide has an oxidation degree of 5 to 50%.

The present invention also relates to a method for preparing an oxidation reaction mixture, comprising the steps of: I) mixing an oxidant aqueous solution and a polysaccharide aqueous solution to obtain an oxidation reaction mixture; II) washing the oxidation reaction mixture with ethanol for several times, filtering and drying to obtain a powdery oxidized polysaccharide; And III) coating a surface of a pretreated catheter with an aqueous solution of oxidized polysaccharide in which the powdery oxidized polysaccharide is dissolved.

The oxidizing agent is at least one selected from the group consisting of hydrogen peroxide, iron nitrate, ozone, peracetic acid, potassium permanganate, potassium peroxodisulfate, potassium peroxodisulfate, sodium periodate, sodium bromate, sodium perborate and sodium percarbonate .

The polysaccharide may be selected from the group consisting of carboxymethylcellulose, carboxyethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, dextrin, dextran, dextran sulfate, alginic acid, hyaluronic acid, chitin, chitosan, gellan gum, glucan, betaglucan, chondroitin sulfate, And at least one selected from the group consisting of glycogen, starch, cellulose, regenerated cellulose, maltodextrin, fructan, galactan and mannan.

The oxidant aqueous solution has a concentration of 0.5 to 40% by weight.

The polysaccharide aqueous solution has a concentration of 1 to 30% by weight.

The oxidation reaction is performed at 25 to 30 DEG C for 1 to 96 hours in a light-shielded atmosphere.

And the concentration of the oxidized polysaccharide aqueous solution is 10 to 40% by weight.

The pretreatment is characterized in that the surface of the catheter is treated by plasma, gamma ray, electron beam, ultraviolet irradiation or radical initiator.

The coating is characterized in that it is carried out by a dip coating method or a spray coating method.

The medical catheter comprising the hydrophilic oxidized polysaccharide coating layer produced according to the present invention has excellent biocompatibility and the lubricity is greatly increased upon insertion into the human body so that the lubricant treatment process is not required before insertion and the side effects such as the perforation of the artery and the blood vessel separation It can be applied to various medical conduits including catheters as well as blood vessels.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a graph showing the lubricity of a medical catheter comprising a hydrophilic polysaccharide coating layer prepared in Examples 1 to 3 of the present invention and a commercialized medical catheter as a control group.
FIG. 2 is a graph showing the influence of molecular weight of oxidized polysaccharide on lubricity in a medical catheter comprising a hydrophilic oxidizing polysaccharide coating layer according to the present invention. FIG.
3 is a graph showing the effect of the degree of oxidation of polysaccharides on lubricity in a medical catheter comprising a hydrophilic polysaccharide coating layer according to the present invention.

Hereinafter, a medical catheter including a hydrophilic polysaccharide coating layer according to the present invention and a method for producing the same will be described in detail.

The present invention provides a medical catheter characterized in that the surface is coated with a hydrophilic oxidizing polysaccharide.

The oxidized polysaccharide may be selected from the group consisting of carboxymethylcellulose, carboxyethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, dextrin, dextran, dextran sulfate, alginic acid, hyaluronic acid, chitin, chitosan, gellan gum, glucan, betaglucan, chondroitin sulfate Means one in which at least one polysaccharide selected from the group consisting of glycogen, starch, cellulose, regenerated cellulose, maltodextrin, fructan, galactan and mannan is oxidized by oxidation reaction.

Generally, when polysaccharides are oxidized by an oxidizing agent or the like, the aliphatic ring structure is opened (ring-opening), and the hydroxy group of the polysaccharide is changed to an aldehyde group. By using this, it is possible to treat the surface of the substrate by inducing chemical bonding. Since 90% of the blood constituting the blood is composed of water, the surface of the catheter is treated with the oxidizing polysaccharide to form a hydrophilic surface, thereby reducing the friction between the catheter surface and the blood vessel wall. Thus, without using any other lubricant, Allowing insertion and movement to the site of the lesion. In addition, since the oxidized polysaccharide is hydrophilic, the surface-treated catheter not only reduces the risk of thrombosis upon contact with the blood, but also facilitates movement by the formation of the meninges. Therefore, Thus reducing the risk of perforation and damage to the vascular wall. In addition, the oxidized polysaccharide treated on the surface of the catheter can be decomposed by moisture even if it is partially decomposed or separated, and can be decomposed, separated and discharged in vivo without adverse effects on blood cells and blood vessels because it is water-soluble.

The molecular weight of the oxidized polysaccharide before oxidation is preferably 1,000 to 100,000. If the molecular weight of the polysaccharide is less than 1,000, the hydrophilic effect of the surface of the catheter is low and the lubricity may be deteriorated. When the molecular weight exceeds 100,000, It is difficult or slow in decomposition in vivo, so that it is difficult to discharge and the viscosity of blood may be too high.

The degree of oxidation indicating degree of oxidation of the polysaccharide can be defined as a ratio (%) of conversion of the hydroxyl group of the polysaccharide to aldehyde by oxidation reaction with an oxidizing agent and the like. The oxidizing polysaccharide has an oxidation degree of 5 to 50% . When the degree of oxidation is less than 5%, the number of reaction sites is decreased, and it may be difficult to bond to the surface or only a small amount may be combined to exhibit a desired lubricating effect. When the degree of oxidation exceeds 50% Upon contact with blood, the molecular weight may be too low or elution may result in reduced lubricity.

Examples of the oxidizing agent in the above step I) include 1) selected from the group consisting of hydrogen peroxide, iron nitrate, ozone, peracetic acid, potassium permanganate, potassium peroxodisulfate, potassium peroxodisulfate, sodium periodate, sodium bromate, sodium perborate, More than one species may be used, but the present invention is not limited thereto.

Examples of the polysaccharide in step I) include carboxymethyl cellulose, carboxyethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, dextrin, dextran, dextran sulfate, alginic acid, hyaluronic acid, chitin, chitosan, gellan gum, But is not limited to, at least one selected from the group consisting of beta-glucan, chondroitin sulfate, glycogen, starch, cellulose, regenerated cellulose, maltodextrin, fructan, galactan and mannan.

In the step I), the oxidizing agent is mixed with the polysaccharide in an aqueous solution to perform the oxidation reaction. It is preferable that the oxidizing agent solution has a concentration of 0.5 to 40% by weight and the polysaccharide aqueous solution has a concentration of 1 to 30% by weight. At this time, in order to suppress the irritative oxidation due to light or temperature in the process of inducing the oxidation reaction from the oxidation reaction mixture, it is preferable to carry out the oxidation reaction at 25 to 30 ° C for 1 to 96 hours in a light-shielded atmosphere.

Next, the oxidizing reaction mixture is washed several times with ethanol, filtered and dried to obtain powdery oxidized polysaccharide. Then, the powdery oxidized polysaccharide is uniformly coated on the surface of the catheter by using purified water or physiological saline solution To obtain an aqueous solution of oxidized polysaccharide. When the concentration of the oxidized polysaccharide aqueous solution is less than 10% by weight, the effect of the hydrophilic coating is insignificant. When the concentration of the oxidized polysaccharide is more than 40% by weight, It is difficult to coat them uniformly.

The pretreatment of the surface of the catheter may be performed by plasma, gamma ray, electron beam, ultrasound, or the like before the surface of the catheter is pretreated in order to increase the adhesion of the oxidized polysaccharide to the surface of the catheter, Ultraviolet radiation or radical initiator to form reactive functional groups or radicals on the surface of the catheter. After such pretreatment, the reactive functional groups or radicals formed on the surface of the catheter are chemically bonded to the aldehyde groups of the oxidized polysaccharide, thereby enhancing the adhesion of the catheter surface (substrate) to the oxidized polysaccharide aqueous solution (coating liquid).

Finally, a medical catheter comprising the hydrophilic oxidizing polysaccharide coating layer according to the present invention is prepared by coating an aqueous solution of oxidized polysaccharide on the surface of the pretreated catheter. The coating process may be any conventional coating method, , Ease of coating process and uniformity of coating, dip coating or spray coating is preferable.

The hydrophilic surface treatment process of the medical catheter made through steps I) through III) may be applied not only to a general blood vessel catheter but also to various types of catheters inserted into the body such as catheters, percutaneous catheters, Catheters, catheters for intracranial pressure measurement, dura mater, subarachnoid and extensor plexus catheters, tube for trachea, drug delivery catheter, and intrauterine catheter.

Hereinafter, embodiments according to the present invention will be described in detail with reference to the accompanying drawings.

[Production Examples 1 to 3] Preparation of oxidized polysaccharide powders

An oxidizing reaction mixture was obtained by mixing an aqueous solution of an oxidizing agent and a polysaccharide (molecular weight: 100,000) as shown in the following Table 1 at 25 DEG C for 24 hours in a light shaking incubator at a weight ratio of 2: 8. The oxidation reaction mixture was washed three times with ethanol, filtered and dried to prepare oxidized polysaccharide powders.

Manufacturing example Oxidant aqueous solution Polysaccharide aqueous solution Oxidation degree Production Example 1 1% by weight sodium periodate 10% by weight carboxymethylcellulose 30% Production Example 2 1% by weight sodium periodate 20% by weight of alginic acid 40% Production Example 3 30 wt% hydrogen peroxide 5 wt% glucan 35%

[ Example 1 to 3] Preparation of a medical catheter comprising a coating of oxidized polysaccharide

The oxidized polysaccharide powders obtained in Preparation Examples 1 to 3 were dissolved in purified water to obtain a 20 wt% aqueous solution of oxidized polysaccharide. Then, each of the above oxidized polysaccharide aqueous solutions was spray-coated on the surface of a catheter pretreated with plasma to prepare a catheter comprising the oxidized polysaccharide coating layer.

FIG. 1 is a graph showing the lubricity of a medical catheter comprising a hydrophilic oxidative polysaccharide coating layer prepared in Examples 1 to 3 of the present invention and a commercially available medical catheter as a control group. As a result, according to Examples 1 to 3 of the present invention, After the completed catheter was dried at 25 ° C for 1 hour, the lubricity was evaluated from the result of measurement of the trackability force when the catheter was inserted into the tube using a hydrophilic artificial tube.

As shown in FIG. 1, the medical catheter comprising the hydrophilic polysaccharide coating layer prepared in Examples 1 to 3 of the present invention has a significantly lower force when the catheter is inserted into the tube than the commercialized medical catheter, which is a control group, It can be confirmed that the lubricity is significantly improved as compared with the medical catheter.

In order to investigate the effect of the molecular weight of the polysaccharide on the lubricity of the catheter in the medical catheter comprising the hydrophilic oxidative polysaccharide coating layer according to the present invention, the catheter prepared in Example 2, The results of measurement of the trackability force when inserting the tube into the tube are shown in Fig.

As shown in FIG. 2, the higher the molecular weight of the polysaccharide, the higher the force applied when the catheter is inserted into the tube, and the lubricity is lowered.

In order to investigate the effect of the degree of oxidation of the polysaccharide on the lubricity in the medical catheter comprising the hydrophilic oxidizing polysaccharide coating layer according to the present invention, the catheter manufactured according to Example 3, The results of the measurement of the trackability force when inserting the test piece into the test piece are shown in FIG.

As shown in FIG. 3, the lower the degree of oxidation of the polysaccharide, the higher the force applied when the catheter was inserted into the tube, and the lower the lubricity, while the higher the degree of oxidation of the polysaccharide, the higher the lubricity.

Therefore, the medical catheter comprising the hydrophilic oxidized polysaccharide coating layer prepared according to the present invention is excellent in biocompatibility, and the lubricity is greatly increased upon insertion into the human body, so that the lubricant treatment process is not required before insertion, It can be applied to various medical ducts including catheters as well as blood vessels because side effects do not occur.

Claims

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I) at least one oxidant aqueous solution selected from the group consisting of hydrogen peroxide, iron nitrate, ozone, peracetic acid, potassium permanganate, potassium peroxodisulfate, potassium peroxodisulfate, sodium periodate, sodium bromate, sodium perborate and sodium percarbonate Obtaining an oxidation reaction mixture by mixing an aqueous solution of a polysaccharide and performing an oxidation reaction at 25 to 30 ° C for 1 to 96 hours in a light-blocked atmosphere;
II) washing the oxidation reaction mixture with ethanol for several times, filtering and drying to obtain a powdery oxidized polysaccharide; And
III) coating a surface of a catheter pretreated with plasma with an aqueous solution of oxidized polysaccharide in which the powdery oxidizing polysaccharide is dissolved.

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The composition of claim 5, wherein the polysaccharide is selected from the group consisting of carboxymethylcellulose, carboxyethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, dextrin, dextran, dextran sulfate, alginic acid, hyaluronic acid, chitin, chitosan, gellan gum, Wherein the at least one drug is at least one selected from the group consisting of beta-glucan, chondroitin sulfate, glycogen, starch, cellulose, regenerated cellulose, maltodextrin, fructan, galactan and mannan.

The method of manufacturing a medical catheter according to claim 5, wherein the oxidant aqueous solution has a concentration of 0.5 to 40% by weight.

6. The method according to claim 5, wherein the polysaccharide aqueous solution has a concentration of 1 to 30% by weight.

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6. The method of claim 5, wherein the oxidized polysaccharide aqueous solution has a concentration of 10 to 40% by weight.

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6. The method of claim 5, wherein the coating is performed by a dip coating method or a spray coating method.