CN116139339A - A kind of artificial blood vessel with coating and preparation method thereof - Google Patents

Abstract

The present application discloses a preparation method of a coated artificial blood vessel and its coating. The preparation method of the artificial blood vessel coating includes the following steps: heating and melting the polyhydroxyalkanoate polymer to obtain a molten polymer; The molten polymer is mixed with glycerin to obtain a coating solution; the coating solution is applied to the surface of the artificial blood vessel to be coated through the coating operation to obtain the artificial blood vessel coating; the artificial blood vessel The coating is subjected to natural cooling operation. The artificial blood vessel obtained by the above preparation method of the artificial blood vessel coating has the performance of anti-leakage and anti-blood seepage, and has the advantages of better biocompatibility and compliance, and higher safety.

Description

A kind of artificial blood vessel with coating and preparation method thereof

technical field

The invention relates to the technical field of artificial blood vessels, in particular to a coated artificial blood vessel and a preparation method of the coating thereof.

Background technique

Vascular replacement is one of the methods widely used in the treatment of atherosclerotic diseases, infection and traumatic vascular injury. At present, hundreds of thousands of coronary and peripheral arterial vascular replacements are performed every year in the world. The replaced vessel must function immediately without any "maturation period" to be fully competent in terms of mechanical strength or inflammatory properties. Vascular substitutes include autologous vessels, xenografts, allografts, and artificial vessels. Autologous blood vessels have many problems such as limited supply of blood vessels, infection, and diameter mismatch.

The artificial blood vessel woven with polybutylene terephthalate (PET) fibers is a kind of artificial blood vessel widely used at present, and it has good mechanical properties and compliance. A PET fiber consists of multiple strands of PET monofilaments. Because there are sub-micron to micron-sized pores between PET monofilaments and PET fiber bundles, there are problems of blood leakage and bleeding in artificial blood vessels woven directly from PET fibers. The first solution is to clean the PET artificial blood vessels before surgery Pre-coagulation is to pre-infiltrate the artificial blood vessel with the patient's blood. After the artificial blood vessel is taken out, the blood will coagulate on the surface of the artificial blood vessel and block the pores of the artificial blood vessel. This method increases the work of the doctor and brings inconvenience to the operation. The risk of blood vessels being polluted by the environment has basically eliminated this method so far. The second method is to coat the artificial blood vessel. After the coating material forms a film, it completely covers the pores on the surface of the artificial blood vessel. At present, the commonly used coating materials for artificial blood vessel products on the market include collagen, gelatin (decomposition of collagen) plasticized with glycerin. material) and silk fibroin. Current sources of medical collagen and gelatin mainly come from traceable cattle or pigs, which are expensive, difficult to prepare, and there are risks of animal-derived viruses. Artificial blood vessels after silk fibroin coating have the problem of hardening, so there is a problem of poor adaptability to human blood vessels. In addition, the artificial blood vessel coating is prone to trace residual solvents, which may cause potential harm to the human body.

Contents of the invention

The purpose of the present invention is to overcome the deficiencies in the prior art and provide a coated artificial Process for the preparation of blood vessels and coatings thereof.

The purpose of the present invention is achieved through the following technical solutions:

A preparation method for an artificial blood vessel coating, comprising the following steps:

heating and melting the polyhydroxyalkanoate polymer to obtain a molten polymer;

Adding the molten polymer to glycerin for mixing operation to obtain a coating solution;

Spraying the coating solution onto the outer surface of the artificial blood vessel to be coated to obtain the artificial blood vessel coating;

A natural cooling operation is performed on the artificial blood vessel coating.

In one of the embodiments, the coating operation adopts a spraying method or a pouring method.

In one embodiment, the polyhydroxyalkanoate polymer is polyhydroxyalkanoate homopolymer or polyhydroxyalkanoate copolymer.

In one embodiment, the polyhydroxyalkanoate polymer has a molecular weight of 1000Da to 1000000Da.

In one of the embodiments, the hydroxyalkanoate monomers in the polyhydroxyalkanoate polymer include short-chain hydroxyalkanoate monomers, medium-chain hydroxyalkanoate monomers and long-chain hydroxyalkanoate monomers .

In one embodiment, the melting temperature in the heating and melting operation is 38°C-200°C.

In one embodiment, the mass fraction of the polyhydroxyalkanoate polymer in the coating solution is 1%-100%.

In one embodiment, the mass fraction of glycerin in the coating solution is 0%-99%.

In one embodiment, the weight ratio of the artificial blood vessel coating to the PET substrate in the artificial blood vessel to be coated is 5% to 200%.

The present application also provides a coated artificial blood vessel, which is prepared by the preparation method of the artificial blood vessel coating described in any one of the above embodiments.

Compared with the prior art, the present invention has at least the following advantages:

(1) In the preparation method of the artificial blood vessel coating of the present invention, the polyhydroxyalkanoate polymer is heated and melted first, so that the polyhydroxyalkanoate polymer reaches a uniform melting state, thereby facilitating the formation of an artificial blood vessel that is easy to spray. Blood vessel coating liquid; then the polyhydroxyalkanoate polymer in molten state is added to glycerol for mixing operation, on the one hand, it can enhance the fluidity and film-forming property of polyhydroxyalkanoate polymer, and facilitate the formation of tightness and stability. Good artificial blood vessel coating; on the other hand, using glycerin as a solvent instead of other various chemical solvents can effectively avoid the potential harm of trace residual solvents to the human body and improve the safety of artificial blood vessels; then use the coating operation to coat the coating The solution is sprayed onto the surface of the artificial blood vessel to be coated, and then the natural cooling operation can effectively improve the uniformity and stability of the artificial blood vessel coating; in addition, the coating can make the artificial blood vessel realize no bleeding and no bleeding during the operation , and the coated artificial blood vessel has suitable softness and compliance.

(2) In the preparation method of the artificial blood vessel coating of the present invention, the polyhydroxyalkanoate polymer solution is adopted as the coating material of the artificial blood vessel, so that the artificial blood vessel has the advantages of biodegradability and good biocompatibility; and the above-mentioned Coating materials are available from a wide variety of sources.

Description of drawings

Fig. 1 is a flow chart of the preparation method of the artificial blood vessel coating in the embodiment of the present application.

Detailed ways

The application is described in detail below. While specific embodiments of the present application have been shown, it should be understood that the application can be implemented in various forms and should not be limited by the embodiments set forth herein. Rather, these embodiments are provided so that the present application can be more thoroughly understood, and the scope of the present application can be fully conveyed to those skilled in the art.

It should be noted that "comprising" or "including" mentioned throughout the specification and claims is an open term, so it should be interpreted as "including but not limited to". The subsequent description of the specification is a preferred implementation mode for implementing the present application, but the description is for the purpose of the general principle of the specification, and is not intended to limit the scope of the present invention. The scope of protection of the present application should be defined by the appended claims.

The present application provides a preparation method of an artificial blood vessel coating. The preparation method of the above artificial blood vessel coating comprises the following steps: heating and melting the polyhydroxyalkanoate polymer to obtain a molten polymer; adding the molten polymer to glycerin for a mixing operation to obtain a coating solution; The coating solution is sprayed onto the outer surface of the artificial blood vessel to be coated to obtain the artificial blood vessel coating; and the artificial blood vessel coating is naturally cooled.

In the preparation method of the above-mentioned artificial blood vessel coating, the polyhydroxyalkanoate polymer is heated and melted first, so that the polyhydroxyalkanoate polymer reaches a uniform melting state, which is conducive to the formation of an easy-to-spray artificial blood vessel coating liquid ; Then add the polyhydroxyalkanoate polymer in the molten state to glycerin for mixing operation, on the one hand, it can enhance the fluidity and film-forming properties of the polyhydroxyalkanoate polymer, and facilitate the formation of artificial blood vessels with better tightness and stability Coating; on the other hand, using glycerin as a solvent instead of other various chemical solvents can effectively avoid the potential harm of trace residual solvents to the human body and improve the safety of artificial blood vessels; Coating the outer surface of the artificial blood vessel, and then performing natural cooling operation, can effectively improve the uniformity and stability of the artificial blood vessel coating; in addition, the coating can make the artificial blood vessel realize no blood leakage or bleeding during the operation, and the coating The artificial blood vessel after layering has suitable softness and compliance. Further, in the preparation method of the artificial blood vessel coating of the present application, the polyhydroxyalkanoate polymer solution is used as the coating material of the artificial blood vessel, so that the artificial blood vessel has the advantages of biodegradability and good biocompatibility; and the above-mentioned Coating materials are available from a wide variety of sources.

Please refer to Fig. 1, in order to better understand the preparation method of the artificial blood vessel coating of the present application, the preparation method of the artificial blood vessel coating of the present application is further explained below, the preparation method of the artificial blood vessel coating of one embodiment includes Follow the steps below:

S100, heating and melting the polyhydroxyalkanoate polymer to obtain a molten polymer.

It should be noted that polyhydroxyalkanoates (PHAs) are the only bioplastics that are completely synthesized by a variety of microorganisms under unbalanced growth conditions. According to the total number of carbon atoms present in the side chains of the PHA monomers, PHAs are broadly classified into three types, short-chain (SCL), medium-chain (MCL) and long-chain (LCL) PHAs. The SCL-PHA monomer contains no more than 5 carbon atoms, the MCL-PHA monomer contains 6-14 carbon atoms, and the LCL-PHA monomer has more than 14 carbon atoms. Bioplastics such as PHAs have attracted extensive attention due to their biodegradable, biocompatible, and thermoplastic properties, and can be used as bioimplant materials, manufacturing of bone marrow scaffolds, orthopedic needles, sutures, adhesion barriers, scaffolds, repairs, etc. patch etc. Experimental studies have shown that PHAs materials support cell adhesion, migration, proliferation, and improve the interaction between cells and material interfaces, support the endothelialization of artificial blood vessels, and have good film-forming properties. Therefore, PHAs coated on the surface of artificial blood vessels, It has good anti-leakage and anti-seepage functions. Following is the chemical structural formula of PHA in the present embodiment:

In short-chain PHA (SCL-PHA), R is an alkyl chain containing 0-2 C atoms, n is 0-3; in medium-chain PHA (MCL-PHA), R is an alkyl chain containing 3-11 C atoms The alkyl chain of atoms, n is 0-1; in the long-chain PHA (LCL-PHA), R is an alkyl chain containing 12-15 C atoms, n is 1.

In this embodiment, the polyhydroxyalkanoate polymer solution is used as the coating material of the artificial blood vessel, which can make the artificial blood vessel have the advantages of biodegradability and good biocompatibility; and the above-mentioned coating materials come from a wide range of sources, Easy access. Further, the polyhydroxyalkanoate polymer is heated and melted first, so that the polyhydroxyalkanoate polymer reaches a uniform melting state, thereby facilitating the formation of an easy-to-spray artificial blood vessel coating liquid.

S200, adding the melted polymer into glycerin to perform a mixing operation to obtain a coating solution.

It is understandable that glycerin, also known as glycerol, has a chemical formula of C3H8O3, is colorless, odorless, sweet, and has a clear and viscous liquid appearance. It is an organic substance that can absorb moisture from the air, as well as hydrogen sulfide, hydrogen cyanide and sulfur dioxide. Most of the existing artificial blood vessel coating solutions use various chemical solvents, so there is a problem of potential harm to the human body caused by trace residual solvents after the coating solution is formed into a film. In order to further improve the safety of the artificial blood vessel coating solution, in this embodiment, the molten polymer is added to glycerin for mixing operation, on the one hand, the fluidity and film-forming properties of the polyhydroxyalkanoate polymer can be enhanced, and it is convenient to form a compact Artificial blood vessel coating with better stability and stability; on the other hand, using glycerin as a solvent instead of other various chemical solvents can effectively avoid the potential harm of trace residual solvents to the human body and improve the safety of artificial blood vessels.

S300. Apply the coating solution to the surface of the artificial blood vessel to be coated through a coating operation to obtain an artificial blood vessel coating.

It can be understood that the artificial blood vessel woven with polybutylene terephthalate (PET) fibers is a widely used artificial blood vessel at present, and it has good mechanical properties and compliance. A PET fiber consists of multiple strands of PET monofilaments. Because there are sub-micron to micron-sized pores between PET monofilaments and PET fiber bundles, there are problems of blood leakage and bleeding in artificial blood vessels woven directly from PET fibers. The first solution is to clean the PET artificial blood vessels before surgery Pre-coagulation is to pre-infiltrate the artificial blood vessel with the patient's blood. After the artificial blood vessel is taken out, the blood will coagulate on the surface of the artificial blood vessel and block the pores of the artificial blood vessel. This method increases the work of the doctor and brings inconvenience to the operation. The risk of blood vessels being polluted by the environment has basically eliminated this method so far. The second method is to coat the artificial blood vessel. After the coating material forms a film, it completely covers the pores on the surface of the artificial blood vessel. At present, the commonly used coating materials for artificial blood vessel products on the market include collagen, gelatin (decomposition of collagen) plasticized with glycerin. material) and silk fibroin. Current sources of medical collagen and gelatin mainly come from traceable cattle or pigs, which are expensive, difficult to prepare, and there are risks of animal-derived viruses. In order to further improve the safety of artificial blood vessels and the effect of preventing blood leakage and blood seepage, in this embodiment, the specific method of coating operation is to disperse the coating solution into uniform and fine mist droplets through a spray gun, and then spray on the surface to be coated. layer of the outer surface of the artificial blood vessel, so that the polyhydroxyalkanoate coating material has better uniformity in the blood vessel, and can effectively improve the film-forming efficiency of the artificial blood vessel coating, and effectively improve the anti-leakage and anti-leakage properties of the artificial blood vessel. Anti-seepage effect, and at the same time avoid the hardening of artificial blood vessels caused by silk fibroin coating, thereby further improving the safety of artificial blood vessels.

S400, performing a natural cooling operation on the coating of the artificial blood vessel.

It can be understood that the coating solution is dispersed into uniform and fine droplets by a spray gun, and then sprayed on the outer surface of the artificial blood vessel to be coated, so that the polyhydroxyalkanoate coating material has better uniformity in the blood vessel , and can effectively improve the film-forming efficiency of the artificial vascular coating. In order to further promote the film-forming effect of polyhydroxyalkanoate polymers in artificial blood vessels, in this embodiment, the artificial blood vessel coating is subjected to natural cooling operation, which can effectively volatilize the solvent in the coating solution, and at the same time ensure that the coating The components in the solution will not be destroyed, thereby effectively improving the film-forming effect of the polyhydroxyalkanoate polymer in the artificial blood vessel, and at the same time effectively improving the tightness and stability of the coating in the artificial blood vessel to achieve better anti-corrosion Leakage anti-seepage blood effect.

In one embodiment, the artificial blood vessel to be coated is a PET artificial blood vessel. It can be understood that the PET artificial blood vessel is an artificial blood vessel woven from polybutylene terephthalate (PET) fibers, and the PET artificial blood vessel has good mechanical properties and compliance. However, PET fibers are composed of multiple strands of PET monofilaments, and there are submicron to micron pores between PET monofilaments and PET fiber bundles, and there are problems of blood leakage and bleeding in artificial blood vessels woven directly from PET fibers . In order to ensure that the artificial blood vessel has good mechanical properties and compliance, and at the same time solve the problem of blood leakage and bleeding in the artificial blood vessel, in this embodiment, the artificial blood vessel to be coated is a PET artificial blood vessel, and the PET The artificial blood vessel is immersed in the polyhydroxyalkanoate polymer solution, and the fiber and monofilament of the artificial blood vessel are fully infiltrated by the solution, and then dried to form a polyhydroxyalkanoate coating, which is effectively combined with the PET artificial blood vessel, so as to ensure the artificial While the blood vessel has good mechanical properties and compliance, it also solves the problems of blood leakage and bleeding in the artificial blood vessel.

In one embodiment, the coating operation is by spraying or pouring. In this embodiment, the coating liquid is evenly sprayed on the outer surface of the artificial blood vessel by spraying, and the artificial blood vessel is continuously and slowly rotated along the axis during spraying to ensure that the coating liquid is evenly sprayed on the outer surface of the artificial blood vessel and penetrates into the inner surface , so that the coating liquid can penetrate from the outside to the inside to form a film, and spraying from the outside is easier to operate, ensuring that every part of the artificial blood vessel, even the corners and edges, can fully spray the coating liquid, thereby improving the film formation of the artificial blood vessel coating Consistency; further, the coating liquid can also be evenly coated on the inner surface of the artificial blood vessel in a perfusion manner and spread to the outer surface, so that the coating liquid can penetrate from the inside to the outside to form a film, so that the basal layer of the artificial blood vessel The coating liquid is more uniform and compact, thereby further improving the anti-leakage and anti-seepage effect of the coating, and at the same time improving the durability of the artificial blood vessel to be coated.

In one embodiment, the polyhydroxyalkanoate polymer is polyhydroxyalkanoate homopolymer or polyhydroxyalkanoate copolymer. Understandably, polyhydroxyalkanoates (PHAs) are the only bioplastics that are entirely synthesized by diverse microorganisms under unbalanced growth conditions. According to the total number of carbon atoms present in the side chains of the PHA monomers, PHAs are broadly classified into three types, short-chain (SCL), medium-chain (MCL) and long-chain (LCL) PHAs. The SCL-PHA monomer contains no more than 5 carbon atoms, the MCL-PHA monomer contains 6-14 carbon atoms, and the LCL-PHA monomer has more than 14 carbon atoms. Bioplastics such as PHAs have attracted extensive attention due to their biodegradable, biocompatible, and thermoplastic properties, and can be used as bioimplant materials, manufacturing of bone marrow scaffolds, orthopedic needles, sutures, adhesion barriers, scaffolds, repairs, etc. patch etc. Using the polyhydroxyalkanoate polymer solution as the coating material of the artificial blood vessel can make the artificial blood vessel have the advantages of biodegradability and good biocompatibility. In order to improve the processability of polyhydroxyalkanoate polymers in artificial blood vessels, in this embodiment, polyhydroxyalkanoate polymers are polyhydroxyalkanoate homopolymers or polyhydroxyalkanoate copolymers, preferably , the polyhydroxyalkanoate polymer is a polyhydroxyalkanoate copolymer. The polymerization reaction involving two or more monomers is called copolymerization, and the resulting product contains two or more monomer units, which is called copolymer. The polyhydroxyalkanoate copolymer has good processing and use performance, so that the processing performance of the polyhydroxyalkanoate polymer in artificial blood vessels can be improved.

In order to further improve the stability of the polyhydroxyalkanoate homopolymer or copolymer, in one embodiment, the molecular weight of the polyhydroxyalkanoate homopolymer or copolymer in the polyhydroxyalkanoate coating is 1000Da-1000000Da . In this embodiment, when the molecular weight of the polyhydroxyalkanoate homopolymer or copolymer is 1000Da-1000000Da, it can be more conducive to the interweaving between polyhydroxyalkanoate polymer molecules, and it is also conducive to improving the artificial blood vessel. Coating biodegradability.

In one embodiment, the hydroxyalkanoate monomers in the polyhydroxyalkanoate polymer include short-chain hydroxyalkanoate monomers, medium-chain hydroxyalkanoate monomers and long-chain hydroxyalkanoate monomers. It should be noted that, according to the monomer composition of PHA, it can be divided into: short chain PHA (scl-PHA: short chain length PHA), whose monomer composition is 3-5 C atoms; medium and long chain PHA (mcl-PHA). :medium chain lengthPHA), whose monomer composition is 6-16C atoms; short-chain medium- and long-chain copolymerized PHA (scl-mcl-PHA), formed by copolymerization of short-chain and medium-long-chain monomers. In this embodiment, the hydroxyalkanoate monomers in the polyhydroxyalkanoate polymer include short-chain hydroxyalkanoate monomers, medium-chain hydroxyalkanoate monomers and long-chain hydroxyalkanoate monomers, and the PHA The physical properties are closely related to its molecular composition and monomer structure. Short-chain PHA has high crystallinity and exhibits good rigidity; medium- and long-chain PHA has low crystallinity and exhibits good elasticity.

In one embodiment, the melting temperature in the heating and melting operation is 38°C-200°C. It can be understood that by heating and melting the polyhydroxyalkanoate polymer first, the polyhydroxyalkanoate polymer can reach a uniform molten state, which is beneficial to the formation of an easy-to-spray artificial blood vessel coating liquid. However, if the melting temperature in the heating and melting operation is too low, the polyhydroxyalkanoate polymer is likely to fail to reach a molten state; if the melting temperature in the heating and melting operation is too high, the structure of the polyhydroxyalkanoate polymer is easily destroyed. . In order to further improve the stability of the heating and melting operation of the polyhydroxyalkanoate polymer, in this embodiment, the melting temperature in the heating and melting operation is 38°C to 200°C, so that the polyhydroxyalkanoate polymer is fully melted to achieve a uniform The melting state of the polyhydroxyalkanoate polymer is guaranteed at the same time, so as to further improve the stability of the heating and melting operation of the polyhydroxyalkanoate polymer.

In one embodiment, the mass fraction of the polyhydroxyalkanoate polymer in the coating solution is 1%-100%. It can be understood that if the mass fraction of the polyhydroxyalkanoate polymer in the coating solution is too low, it is easy to make the film-forming property of the artificial blood vessel coating poor, the spray adhesion is poor, and it is easy to cause the anti-leakage of the artificial blood vessel coating. The anti-bleeding effect is poor; if the mass fraction of polyhydroxyalkanoate polymer in the coating solution is too high, it is not conducive to the spraying operation of the coating solution, making it difficult for the spray gun to disperse the coating solution into a uniform and fine mist Drops are not conducive to the combination of the coating and the artificial blood vessel. In order to further improve the spraying effect and film-forming effect of the polyhydroxyalkanoate polymer solution, in this embodiment, the mass fraction of the polyhydroxyalkanoate polymer in the coating solution is 1% to 100%, so that the polyhydroxyalkanoate The ester polymer solution has better uniformity and atomization, so that the coating solution can be evenly sprayed on the outer surface of the artificial blood vessel, and has better adhesion and film-forming properties, and further improves the polyhydroxyalkanoic acid. Spraying and filming effects of ester polymer solutions.

In one embodiment, the mass fraction of glycerin in the coating solution is 0%-99%. It can be understood that if the mass fraction of glycerin in the coating solution is too low, the uniformity of the polyhydroxyalkanoate polymer in the coating solution is likely to be poor, thereby affecting the anti-seepage and anti-leakage effect of the artificial blood vessel coating; If the mass fraction of glycerin in the coating solution is too high, the viscosity of the coating solution is likely to be low, resulting in low adhesion of the coating solution after it is sprayed on the surface of the artificial blood vessel. In order to further improve the spraying effect and adhesion stability of the polyhydroxyalkanoate polymer solution, in this embodiment, the mass fraction of glycerin in the coating solution is 0% to 99%, so that the uniformity of the coating solution is better, Moreover, the viscosity is good, and it is easy to spray, so that the spraying effect and adhesion stability of the polyhydroxyalkanoate polymer solution can be further improved, thereby improving the anti-seepage and anti-leakage effect of the artificial blood vessel coating.

In one embodiment, the weight ratio of the artificial blood vessel coating to the PET base material in the artificial blood vessel to be coated is 5% to 200%. By controlling the weight ratio of the coating and the PET base material of the artificial blood vessel, the combination of the coating and the PET base material of the artificial blood vessel can be effectively improved, so that the coating has good film-forming property, and can be coated on the surface of the artificial blood vessel with good Excellent anti-leakage and anti-seepage function.

In one of the embodiments, the temperature in the free cooling operation does not exceed 37°C. It can be understood that the coating solution is dispersed into uniform and fine mist droplets by a spray gun, and then sprayed on the outer surface of the artificial blood vessel to be coated to form a polyhydroxyalkanoate coating, which is effectively combined with the PET artificial blood vessel, thereby While ensuring that the artificial blood vessel has good mechanical properties and compliance, it also solves the problems of blood leakage and bleeding in the artificial blood vessel. However, if the temperature in the natural cooling operation is too high, it is easy to cause damage to the artificial blood vessel, especially the suitable temperature of the artificial blood vessel is within the normal body temperature range of a person. In order to ensure the safety and stability of the artificial blood vessel while ensuring the film-forming effect of the coating, in this embodiment, the temperature in the natural cooling operation does not exceed 37°C. On the one hand, the solvent in the coating solution can be Fully dry and volatilize; on the other hand, it can also ensure the stability and safety of artificial blood vessels.

The present application also provides a coated artificial blood vessel, which is prepared by the preparation method of the artificial blood vessel coating described in any one of the above embodiments.

Artificial blood vessel test:

The water permeability test of artificial blood vessels refers to "YY/T 0500-2021 Cardiovascular Implants, Vascular Prostheses, Tubular Vascular Grafts and Vascular Patches". One end of the artificial blood vessel is fixed on the transparent silicone tube with visible water surface. No water leakage is enough, the other end is closed with a metal clip, and tap water is injected into the silicone tube. Counting from the joint between the artificial blood vessel and the silicone tube, the vertical height of the water column is guaranteed to be 163cm (the corresponding water pressure is 16.0KPa). To test the replenishment of the water column, insert a small-diameter hose connected to the faucet into the top of the silicone tube (unsealed, open to the atmosphere), and measure the volume of water seeping from the artificial blood vessel wall within 10 minutes.

The compliance test of artificial blood vessels refers to "YY/T 0500-2021 Cardiovascular Implants, Vascular Prostheses, Tubular Vascular Grafts and Vascular Patches", and is carried out on the artificial blood vessel compliance tester. Change in inner diameter during shrinkage. The calculation method is as follows: %Compliance=[(RP2-RP1)/RP1]/(P2-P1)×104, where R is the inner diameter of the artificial blood vessel, RP1 is the inner diameter when the pressure is 80mmHg, and RP2 is the inner diameter when the pressure is 120mmHg Inner diameter, P1=80mmHg, P2=120mmHg.

The following describes the coating process by taking a PET artificial blood vessel coating as an example.

Embodiment key factor explanatory table

Example 1

Melt poly-3-hydroxynonanoate homopolymer (P3HN) with a molecular weight of 100,000Da at 90°C to prepare a coating liquid; spray the coating liquid onto the outer surface of the artificial blood vessel, and keep the artificial blood vessel rotating slowly along the axis during spraying ; When the weight of the coating liquid received by the artificial blood vessel reaches the expected weight and accounts for 5% of the blood vessel base material, stop spraying, keep the artificial blood continuously rotating along the axis, and cool naturally.

The prepared artificial blood vessel has a water penetration rate of 0.06ml/cm2/min at 16kPa, which is better than the most widely used imported coated artificial blood vessel on the market (the test value is 0.10ml/cm2/min).

The prepared artificial blood vessel has a compliance of 4.4% at a diastolic pressure of 120mmHg and a systolic pressure of 80mmHg, which is better than the 4.1% measured compliance of the most widely used imported coated artificial blood vessel currently on the market under the same conditions.

Example 2

Melt poly-3-hydroxypentadecanoate (P3HPD) with a molecular weight of 1,000,000Da at 70°C, add glycerin and mix evenly to obtain a coating solution with a ratio of polymer/glycerol (wt)=1:99; spray the coating solution To the outer surface of the artificial blood vessel, the artificial blood vessel keeps rotating slowly along the axis when spraying; when the weight of the coating liquid received by the artificial blood vessel reaches the expected weight and accounts for 200% of the blood vessel base material, stop spraying and keep the artificial blood continuously rotating along the axis , natural cooling.

The prepared artificial blood vessel has a water penetration rate of 0.07ml/cm2/min at 16kPa, which is better than the most widely used imported coated artificial blood vessel on the market (the test value is 0.10ml/cm2/min).

The prepared artificial blood vessel has a compliance of 4.4% at a diastolic pressure of 120mmHg and a systolic pressure of 80mmHg, which is better than the 4.1% measured compliance of the most widely used imported coated artificial blood vessel currently on the market under the same conditions.

Example 3

Melt 3-hydroxybutyric acid/3-hydroxycapric acid copolymer (P(3HB-co-3HD) with a molecular weight of 10000Da at 80°C, add glycerin and mix evenly to obtain a ratio of polymer/glycerin (wt) = 10:90 coating liquid; spray the coating liquid onto the outer surface of the artificial blood vessel, and keep the artificial blood vessel rotating slowly along the axis during spraying; when the weight of the coating liquid received by the artificial blood vessel reaches 100% of the expected weight and accounts for 100% of the blood vessel base material, stop Spraying, keeping the artificial blood continuously rotating along the axis, and cooling naturally.

The prepared artificial blood vessel has a water permeability of 0 at 16kPa, which is better than the most widely used imported artificial blood vessel with coating on the market (the test value is 0.10ml/cm2/min).

The prepared artificial blood vessel has a compliance of 4.2% at a diastolic pressure of 120mmHg and a systolic pressure of 80mmHg, which is comparable to the 4.1% level of compliance measured by the most widely used imported artificial blood vessel with coating on the market under the same conditions .

Example 4

3-hydroxypentanoic acid/3-hydroxyoctadecanoic acid copolymer with a molecular weight of 2000Da

(P(3HV-co-3HOD) was melted at 75°C, added glycerin and mixed uniformly to obtain a coating liquid with a ratio of polymer/glycerin (wt) = 30:70; the coating liquid was sprayed onto the outer surface of the artificial blood vessel, and when spraying The artificial blood vessel keeps rotating slowly along the axial direction; when the weight of the coating liquid received by the artificial blood vessel reaches 70% of the expected weight of the blood vessel base material, the spraying is stopped, and the artificial blood is kept rotating along the axial direction and cooled naturally.

The prepared artificial blood vessel has a water permeability of 0 at 16kPa, which is better than the most widely used imported artificial blood vessel with coating on the market (the test value is 0.10ml/cm2/min).

The prepared artificial blood vessel has a compliance of 4.2% at a diastolic pressure of 120mmHg and a systolic pressure of 80mmHg, which is comparable to the 4.1% level of compliance measured by the most widely used imported artificial blood vessel with coating on the market under the same conditions .

Example 5

3-hydroxydodecanoic acid/3-hydroxyhexadecanoic acid copolymer with a molecular weight of 50000Da

(P(3HDD-co-3HHxD) was melted at 50°C, added glycerin and mixed uniformly to obtain a coating liquid with a ratio of polymer/glycerin (wt) = 50:50; the coating liquid was sprayed on the outer surface of the artificial blood vessel, and when spraying The artificial blood vessel keeps rotating slowly along the axis; when the weight of the coating liquid received by the artificial blood vessel reaches the expected weight and accounts for 30% of the blood vessel base material, stop spraying, keep the artificial blood continuously rotating along the axis, and cool naturally.

The prepared artificial blood vessel has a water permeability of 0 at 16kPa, which is better than the most widely used imported artificial blood vessel with coating on the market (the test value is 0.10ml/cm2/min).

The prepared artificial blood vessel has a compliance of 4.1% at a diastolic pressure of 120mmHg and a systolic pressure of 80mmHg, which is comparable to the 4.1% level of compliance measured by the most widely used imported artificial blood vessel with coating on the market under the same conditions .

It can be seen from Examples 1 to 5 that the artificial blood vessel prepared by the preparation method of the artificial blood vessel coating of the present invention has the lowest water penetration of 0 at 16kPa, which is better than the most widely used imported artificial blood vessel with coating on the market. product (test value 0.10ml/cm2/min). Moreover, the compliance tested under diastolic pressure of 120mmHg and systolic pressure of 80mmHg is 4.1%-4.4%. Under the same conditions, the compliance of the most widely used imported coated artificial vascular product on the market is 4.1%. It shows that the artificial blood vessel prepared by the preparation method of the artificial blood vessel coating of the present invention has better anti-leakage and anti-bleed performance, and has the advantages of better biocompatibility and compliance.

Compared with the prior art, the present invention has at least the following advantages:

(1) In the preparation method of the artificial blood vessel coating of the present invention, the polyhydroxyalkanoate polymer is heated and melted first, so that the polyhydroxyalkanoate polymer reaches a uniform melting state, thereby facilitating the formation of an artificial blood vessel that is easy to spray. Blood vessel coating liquid; then the polyhydroxyalkanoate polymer in molten state is added to glycerol for mixing operation, on the one hand, it can enhance the fluidity and film-forming property of polyhydroxyalkanoate polymer, and facilitate the formation of tightness and stability. Good artificial blood vessel coating; on the other hand, using glycerin as a solvent instead of other various chemical solvents can effectively avoid the potential harm of trace residual solvents to the human body and improve the safety of artificial blood vessels; then spray the coating The solution is sprayed onto the outer surface of the artificial blood vessel to be coated, and then the natural cooling operation can effectively improve the uniformity and stability of the artificial blood vessel coating; in addition, the coating can enable the artificial blood vessel to achieve no blood leakage and no seepage during the operation. blood, and the coated artificial blood vessel has suitable softness and compliance.

(2) In the preparation method of the artificial blood vessel coating of the present invention, the polyhydroxyalkanoate polymer solution is adopted as the coating material of the artificial blood vessel, so that the artificial blood vessel has the advantages of biodegradability and good biocompatibility; and the above-mentioned Coating materials are available from a wide variety of sources.

The above is only a preferred embodiment of the application, and it is not intended to limit the application to other forms. Any skilled person who is familiar with this field may use the technical content disclosed above to change or modify the equivalent of the equivalent change. Example. However, any simple modifications, equivalent changes and modifications made to the above embodiments according to the technical essence of the present application without departing from the content of the technical solution of the present application still belong to the protection scope of the technical solution of the present application.

Claims (10)

1. a preparation method of artificial blood vessel coating, is characterized in that, comprises the following steps: heating and melting the polyhydroxyalkanoate polymer to obtain a molten polymer; Adding the molten polymer to glycerin for mixing operation to obtain a coating solution; Applying the coating solution to the surface of the artificial blood vessel to be coated through a coating operation to obtain the artificial blood vessel coating; A natural cooling operation is performed on the artificial blood vessel coating. 2. The preparation method of artificial blood vessel coating according to claim 1, characterized in that, the coating operation adopts a spraying method or a pouring method. 3 . The preparation method of artificial blood vessel coating according to claim 1 , characterized in that, the polyhydroxyalkanoate polymer is a polyhydroxyalkanoate homopolymer or a polyhydroxyalkanoate copolymer. 4. The preparation method of artificial blood vessel coating according to claim 1, characterized in that, the molecular weight of the polyhydroxyalkanoate polymer is 1000Da to 1000000Da. 5. The preparation method of artificial blood vessel coating according to claim 1, it is characterized in that, the hydroxyalkanoate monomer in the polyhydroxyalkanoate polymer comprises short-chain hydroxyalkanoate monomer, medium-chain hydroxyl Alkanoate monomers and long chain hydroxyalkanoate monomers. 6 . The preparation method of artificial blood vessel coating according to claim 1 , characterized in that, the melting temperature in the heating and melting operation is 38° C. to 200° C. 6 . 7. The preparation method of artificial blood vessel coating according to claim 1, characterized in that, the mass fraction of the polyhydroxyalkanoate polymer in the coating solution is 1%-100%. 8. The preparation method of artificial blood vessel coating according to claim 1, characterized in that, the mass fraction of glycerin in the coating solution is 0%-99%. 9 . The method for preparing an artificial blood vessel coating according to claim 2 , wherein the weight ratio of the artificial blood vessel coating to the PET substrate in the artificial blood vessel to be coated is 5% to 200%. 10. A coated artificial blood vessel, characterized in that it is prepared by the method for preparing artificial blood vessel coating according to any one of claims 1 to 9.

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