阅读说明：本技术 一种柔性聚酯贴片及其制备方法与应用 (Flexible polyester patch and preparation method and application thereof ) 是由 周晶 杨宇恒 罗紫灵 周梓婷 孟月 韩建东 白莹 全大萍 于 2021-08-25 设计创作，主要内容包括：本发明公开了一种柔性聚酯贴片及其制备方法与应用,涉及医学技术领域。本发明所述一种柔性聚酯贴片的制备方法,包括如下步骤：(1)将PCT薄膜裁剪后,包裹在圆管状模具上,加热一段时间后冷却,得到圆管状贴片；(2)将步骤(1)中制备得到的圆管状贴片,加热一段时间后,施加外力捏扁得到临时形状贴片,得到所述柔性聚酯贴片。本发明制备的柔性聚酯贴片片柔性好,通过其形状记忆性能可以较好的贴附在血管内壁,移植过程不容易对血管内壁造成损伤。本发明提供的柔性聚酯贴片相比于血管支架,贴片的厚度薄,容易降解,不会残留在血管中形成新的堵塞物。(The invention discloses a flexible polyester patch and a preparation method and application thereof, and relates to the technical field of medicine. The invention relates to a preparation method of a flexible polyester patch, which comprises the following steps: (1) cutting the PCT film, wrapping the PCT film on a circular tubular mold, heating for a period of time, and cooling to obtain a circular tubular patch; (2) and (2) heating the round tubular patch prepared in the step (1) for a period of time, and then applying external force to knead the patch flat to obtain a temporary-shaped patch, thus obtaining the flexible polyester patch. The flexible polyester patch sheet prepared by the invention has good flexibility, can be well attached to the inner wall of a blood vessel through the shape memory performance of the flexible polyester patch sheet, and is not easy to damage the inner wall of the blood vessel in the transplanting process. Compared with the vascular stent, the flexible polyester patch provided by the invention is thin in thickness, easy to degrade and free from remaining in blood vessels to form new blockage.)

1. A preparation method of a flexible polyester patch is characterized by comprising the following steps:

(1) cutting the PCT film, wrapping the PCT film on a circular tubular mold, heating for a period of time, and cooling to obtain a circular tubular patch;

(2) and (2) heating the round tubular patch prepared in the step (1) for a period of time, and then applying external force to knead the patch flat to obtain a temporary-shaped patch, thus obtaining the flexible polyester patch.

2. The method for preparing a flexible polyester patch according to claim 1, wherein in the step (1), the PCT film is prepared as follows:

(a) purifying and drying 4- (ethylene glycol ketal) -epsilon-caprolactone and epsilon-caprolactone containing side cyclic ether, weighing a certain content of 4- (ethylene glycol ketal) -epsilon-caprolactone and epsilon-caprolactone containing side cyclic ether, adding stannous octoate, a toluene solution and benzyl alcohol, stirring uniformly, reacting under vacuum to obtain a mixed solution A, and sealing a reaction container after no bubbles are generated for 30 min;

(b) stirring the sealed reaction container in an oil bath at 130 ℃ for 24 hours for reaction, purifying after the reaction is finished, and drying to constant weight to obtain a PCT sample;

(c) and adding methylene dichloride to the PCT sample to dissolve the PCT sample, placing the PCT sample in a mould, and air-drying to obtain the PCT film.

3. The method for preparing a flexible polyester patch according to claim 1, wherein in the step (1), the thickness of the PCT film is 0.05 to 0.2mm, and the outer diameter of the circular tubular mold is 2 to 8 mm.

4. The method for preparing a flexible polyester patch according to claim 1, wherein in the step (1), the heating temperature is 46-56 ℃ and the heating time is 5-15 s; cooling to 20-25 deg.C.

5. The method for preparing a flexible polyester patch according to claim 1, wherein the heating temperature in the step (2) is 32-36 ℃ and the heating time is 1-2 min.

6. A flexible polyester patch prepared by the method of any one of claims 1-5.

7. Use of the flexible polyester patch of claim 6 in the manufacture of an anti-thrombotic patch.

Technical Field

The invention relates to the technical field of medicine, in particular to a flexible polyester patch and a preparation method and application thereof.

Background

Ischemic diseases such as thromboembolism are important factors causing death of the global population every year. The main causes of blood embolism are atherosclerosis caused by the pathological changes of blood vessel walls and the reduction of the inner diameter of the blood vessel. Red blood cells, fibrinogen and platelets in blood are easily adhered to the diseased part, so that the blood vessel is obviously narrowed or even blocked. Which in turn causes a reduction in local blood flow or interruption of blood supply, which if not treated in a timely manner, can lead to death.

At present, two methods are mainly used for treating the blood embolism, one method is to implant a vascular stent at the position of the stenotic blockage of a blood vessel, and the stenotic blockage of the blood vessel is propped open by using the higher elastic modulus and strength of the vascular stent, so that the blood vessel is unblocked again, and normal blood supply is realized. However, the method has the problems that after the stent is implanted, the normal flow of blood is ensured, but because the embolus is not taken out, and if the implanted vascular stent can not be degraded in time, endothelial cells can grow into the stent to form new vascular endothelial tissues, and the stent which can not be degraded in time can become a new obstruction, so that secondary blockage is caused. According to statistics, the restenosis rate of the blood vessel of the patient reaches 15 to 20 percent after the vascular stent is implanted. Another method is to take out the embolus blocking the blood vessel outside the body by mechanical method with an embolectomy device. Most of the blockage can be cleared away by the method, but the method does not repair the hardened blood vessel. In addition, the method has great damage to the vessel wall and is easy to cause secondary damage to the vessel.

In order to ensure normal contraction and expansion of the blood vessel after operation and maintain normal blood supply, the breaking elongation of the vascular graft is more than 60%. Meanwhile, the healing period of vascular repair is about 6 months, and in order to avoid secondary blockage, the vascular graft needs to be degradable, and the degradation period of the vascular graft should be identical with the healing period of vascular repair. The current common in vivo transplantation stents such as polytetrafluoroethylene, polyamide and the like cannot meet the requirement.

Disclosure of Invention

Based on the above, the invention aims to overcome the defects of the prior art and provide a flexible polyester patch and a preparation method and application thereof.

In order to achieve the purpose, the technical scheme adopted by the invention is as follows: a preparation method of a flexible polyester patch comprises the following steps:

(1) cutting the PCT film, wrapping the PCT film on a circular tubular mold, heating for a period of time, and cooling to obtain a circular tubular patch;

(2) and (2) heating the round tubular patch prepared in the step (1) for a period of time, and then applying external force to knead the patch flat to obtain a temporary-shaped patch, thus obtaining the flexible polyester patch.

The invention provides a preparation method of a flexible polyester patch, which mainly adopts a mode of heating and cooling twice, better exerts the effect of the flexible polyester patch and achieves a good effect of being attached to blood vessels. The first heating is to soften the PCT film, and the PCT film is cooled to obtain a permanent memory shape; the second heating is to prepare a temporary patch with a small cross section area and a small volume, namely the flexible polyester patch, so that minimally invasive implantation is realized, and the patch is restored to be in a circular tube shape and attached to the inner wall of the blood vessel under the condition of human body temperature after being implanted into a body.

Preferably, in the step (1), the PCT film is prepared as follows:

(a) purifying and drying 4- (ethylene glycol ketal) -epsilon-caprolactone and epsilon-caprolactone containing side cyclic ether, weighing a certain content of 4- (ethylene glycol ketal) -epsilon-caprolactone and epsilon-caprolactone containing side cyclic ether, adding stannous octoate, a toluene solution and benzyl alcohol, stirring uniformly, reacting under vacuum to obtain a mixed solution A, and sealing a reaction container after no bubbles are generated for 30 min;

(b) stirring the sealed reaction container in an oil bath at 130 ℃ for 24 hours for reaction, purifying after the reaction is finished, and drying to constant weight to obtain a PCT sample;

(c) and adding methylene dichloride to the PCT sample to dissolve the PCT sample, placing the PCT sample in a mould, and air-drying to obtain the PCT film.

The preparation method of the PCT film is prepared according to the method in the literature, namely design synthesis of the elastic polycaprolactone based on side cyclic ether modification and application research of the elastic polycaprolactone in soft tissue engineering.

Preferably, in the step (1), the thickness of the PCT film is 0.05-0.2mm, and the outer diameter of the round tubular mould is 2-8 mm. The thickness of the circular tube patch is flexibly selected according to different use scenes, and a proper circular tube-shaped die is selected according to the outer diameter of a blood vessel which is hardened or blocked.

Preferably, in the step (1), the heating temperature is 46-56 ℃, and the heating time is 5-15 s; cooling to 20-25 deg.C. The heating temperature of the invention is 46-56 ℃, and after a large number of creative tests of the inventor, the invention finds that the PCT film has better softening effect and is easier to shape in the temperature range, and a permanent circular tube-shaped patch is easier to obtain after cooling.

Preferably, in the step (2), the heating temperature is 32-36 ℃, and the heating time is 1-2 min. The heating temperature of the invention is 32-36 ℃, and after a great deal of creative experiments and researches of the inventor, the invention finds that in the temperature range, the molecular chain part moves and is pinched flat by applying external force, so that a temporary shape patch is easier to obtain, and the shape of the permanent circular tube patch after being heated and recovered can not be changed greatly.

In addition, the invention provides the flexible polyester patch prepared by the preparation method of the flexible polyester patch. Furthermore, the invention provides application of the flexible polyester patch in preparing an antithrombotic patch.

Compared with the prior art, the invention has the beneficial effects that: the invention provides a flexible polyester patch, and the degradability and the shape memory performance of the flexible polyester patch can be better exerted through the preparation method of the flexible polyester patch. The flexible polyester patch sheet prepared by the invention has good flexibility, can be well attached to the inner wall of a blood vessel through the shape memory performance of the flexible polyester patch sheet, and is not easy to damage the inner wall of the blood vessel in the transplanting process. Compared with the vascular stent, the flexible polyester patch provided by the invention is thin in thickness, easy to degrade and free from remaining in blood vessels to form new blockage.

Drawings

FIG. 1 is a diagram of the preparation process and application of a flexible polyester patch;

figure 2 is a schematic illustration of the implantation application and degradation of a flexible polyester patch.

Detailed Description

To better illustrate the objects, aspects and advantages of the present invention, the present invention will be further described with reference to the accompanying drawings and specific embodiments.

The PCT film used in the embodiment of the invention is prepared according to a method in a literature, namely design synthesis of elastic polycaprolactone based on side cyclic ether modification and application research of elastic polycaprolactone in soft tissue engineering, wherein the mass ratio of CL to TOSUO is 85: 15 linear PCT;

the preparation method comprises the following steps:

(a) purifying and drying 4- (ethylene glycol ketal) -epsilon-caprolactone and epsilon-caprolactone containing side cyclic ether, weighing a certain content of 4- (ethylene glycol ketal) -epsilon-caprolactone and epsilon-caprolactone containing side cyclic ether, adding stannous octoate, a toluene solution and benzyl alcohol, stirring uniformly, reacting under vacuum to obtain a mixed solution A, and sealing a reaction container after no bubbles are generated for 30 min;

(b) stirring the sealed reaction container in an oil bath at 130 ℃ for 24 hours for reaction, purifying after the reaction is finished, and drying to constant weight to obtain a PCT sample;

(c) 1.5g of PCT sample is put into a rectangular mould with the thickness of 90 x 90mm, 20mL of dichloromethane is added for dissolution, and the mixture is placed in a fume hood for 24 hours, and after the solvent is volatilized, a PCT film with the thickness of 0.18mm can be obtained.

The invention provides embodiments 1-3, and the preparation method of the flexible polyester patch of the embodiments 1-3 is as follows, and the preparation flow is shown in fig. 1:

example 1

A preparation method of a flexible polyester patch comprises the following steps:

(1) cutting a PCT film, wrapping the PCT film on a round tubular mold, heating for a period of time, cooling, wherein the outer diameter of the round tubular mold is 2mm, the heating temperature is 46 ℃, and the heating time is 15 s; cooling to 20 ℃ to obtain a circular tube-shaped patch;

(2) and (2) heating the round tubular patch prepared in the step (1) for a period of time, wherein the heating temperature is 32 ℃, the heating time is 1min, and applying external force to knead the patch flat to obtain a temporary-shaped patch so as to obtain the flexible polyester patch.

Example 2

A preparation method of a flexible polyester patch comprises the following steps:

(1) cutting a PCT film, wrapping the PCT film on a round tubular mold, heating for a period of time, cooling, wherein the outer diameter of the round tubular mold is 8mm, the heating temperature is 56 ℃, and the heating time is 5 s; cooling to 25 ℃ to obtain a circular tube-shaped patch;

(2) and (2) heating the round tubular patch prepared in the step (1) for a period of time, wherein the heating temperature is 36 ℃, the heating time is 2min, and applying external force to knead the patch flat to obtain a temporary-shaped patch so as to obtain the flexible polyester patch.

Example 3

A preparation method of a flexible polyester patch comprises the following steps:

(1) cutting a PCT film, wrapping the PCT film on a round tubular mold, heating for a period of time, cooling, wherein the outer diameter of the round tubular mold is 5mm, the heating temperature is 50 ℃, and the heating time is 10 s; cooling to 25 ℃ to obtain a circular tube-shaped patch;

(2) and (2) heating the round tubular patch prepared in the step (1) for a period of time, wherein the heating temperature is 34 ℃, the heating time is 2min, and applying external force to knead the patch flat to obtain a temporary-shaped patch so as to obtain the flexible polyester patch.

Meanwhile, the invention is provided with comparative examples 1-4, and the preparation method of the flexible polyester patch specifically comprises the following steps:

comparative example 1

A preparation method of a flexible polyester patch comprises the following steps:

(1) cutting a PCT film, wrapping the PCT film on a round tubular mold, heating for a period of time, cooling, wherein the outer diameter of the round tubular mold is 5mm, the heating temperature is 60 ℃, and the heating time is 10 s; cooling to 25 ℃ to obtain a circular tube-shaped patch;

(2) and (2) heating the round tubular patch prepared in the step (1) for a period of time, wherein the heating temperature is 34 ℃, the heating time is 2min, and applying external force to knead the patch flat to obtain a temporary-shaped patch so as to obtain the flexible polyester patch.

Comparative example 2

A preparation method of a flexible polyester patch comprises the following steps:

(1) cutting a PCT film, wrapping the PCT film on a round tubular mold, heating for a period of time, cooling, wherein the outer diameter of the round tubular mold is 5mm, the heating temperature is 40 ℃, and the heating time is 10 s; cooling to 25 ℃ to obtain a circular tube-shaped patch;

(2) and (2) heating the round tubular patch prepared in the step (1) for a period of time, wherein the heating temperature is 34 ℃, the heating time is 2min, and applying external force to knead the patch flat to obtain a temporary-shaped patch so as to obtain the flexible polyester patch.

Comparative example 3

A preparation method of a flexible polyester patch comprises the following steps:

(1) cutting a PCT film, wrapping the PCT film on a round tubular mold, heating for a period of time, cooling, wherein the outer diameter of the round tubular mold is 5mm, the heating temperature is 50 ℃, and the heating time is 10 s; cooling to 25 ℃ to obtain a circular tube-shaped patch;

(2) and (2) heating the round tubular patch prepared in the step (1) for a period of time, wherein the heating temperature is 30 ℃, the heating time is 2min, and applying external force to knead the patch flat to obtain a temporary-shaped patch so as to obtain the flexible polyester patch.

Comparative example 4

A preparation method of a flexible polyester patch comprises the following steps:

(1) cutting a PCT film, wrapping the PCT film on a round tubular mold, heating for a period of time, cooling, wherein the outer diameter of the round tubular mold is 5mm, the heating temperature is 50 ℃, and the heating time is 10 s; cooling to 25 ℃ to obtain a circular tube-shaped patch;

(2) and (2) heating the round tubular patch prepared in the step (1) for a period of time, wherein the heating temperature is 42 ℃, the heating time is 2min, and applying external force to knead the patch flat to obtain a temporary-shaped patch so as to obtain the flexible polyester patch.

The preparation methods and application diagrams of the flexible polyester patches of the embodiments and the comparative examples are shown in fig. 1, the flexible polyester patches of the embodiments 1 to 3 are good in flexibility, can be well attached to the inner wall of a blood vessel through the shape memory performance of the flexible polyester patches, and are not easy to damage the inner wall of the blood vessel in the transplanting process. Compared with the vascular stent, the flexible polyester patch prepared in the embodiment 1-3 of the invention has the advantages of thin thickness, easy degradation and no residue in blood vessels to form new blockage.

The temperature of heating in step (1) in comparative example 1 is 60 ℃, and if heating is carried out at 60 ℃, because the temperature is far higher than the melting temperature of the material (Tg ═ 44.3 ℃), the whole molecular chain can move without limitation, so that the film is directly melted into a mass during heating, and a round tube with a permanent shape cannot be obtained; in the comparative example 2, the heating temperature in the step (1) is 40 ℃, when the heating temperature is 40 ℃, the movement degree of molecular chains is small, and the film is difficult to close to form a circular tubular patch; in comparative example 3, the heating temperature in step (2) was 34 ℃, most of the crystals were not melted during the secondary heating and remained crystalline, resulting in fewer rearranged polymer chains, difficulty in fixing the shape, and difficulty in obtaining a patch with a temporary shape; in comparative example 4, step (2) was heated to 42 ℃ and most of the crystals were melted and more polymer chains were released to rearrange. The molecular chains for memorizing the permanent shape are few, the driving force for shape recovery is small, and the permanent shape is difficult to recover, so that the fitting degree is low.

Test example 1 test for degree of adhesion

The test process comprises the following steps: in the preparation of the flexible polyester patches of examples 1-3, the cross-sectional area S1 of the tubular patch obtained in step (1) was recorded; the cross-sectional area S2 of the temporary shape patch obtained in step (2); keeping the temporary shape patch (namely the flexible polyester patch) at 37-40 ℃ for a period of time to obtain a recovered flexible polyester patch, wherein the cross sectional area is marked as S3;

example 1-3 preparation method of flexible polyester patch, in the actual test process, 3 sets of tests were performed respectively;

the test formula is as follows: shape recovery ratio Rr ═ S3-S2)/(S1-S2;

and (3) test results: as described in table 1 below;

table 1 results of the adhesion test

In the practical application process of the flexible polyester patch, the shape recovery rate can reach more than 85 percent.

Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention and not for limiting the protection scope of the present invention, and although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.