阅读说明：本技术 一种生物医用材料防钙化的方法 (Anti-calcification method for biomedical material ) 是由 陈大凯 于 2020-02-24 设计创作，主要内容包括：本发明公开了一种生物医用材料防钙化的方法,包括：S1.将戊二醛进行处理,得到高纯度的单体戊二醛；S2.将第一种单体戊二醛溶液的pH调节至5.0-9.0,并将生物医用材料浸泡于第一种单体戊二醛溶液中,保持一定温度且持续保存一定时间；S3.将第一种醇类溶液的pH调节至5.0-9.0,将步骤S2中得到的生物医用材料浸泡于第一种醇类溶液中,保持一定温度且持续保存一定时间；S4.将第二种单体戊二醛溶液的pH调节至5.0-9.0,将步骤S3中得到的生物医用材料浸泡于第二种单体戊二醛溶液中,保持一定温度且持续保存一定时间；S5.将第三种单体戊二醛溶液的pH调节至5.0-9.0,将步骤S4中得到的生物医用材料浸泡于第三种单体戊二醛溶液中,保持一定温度且持续保存,得到防钙化的生物医用材料。(The invention discloses a method for preventing calcification of biomedical materials, which comprises the following steps: s1, treating glutaraldehyde to obtain high-purity monomer glutaraldehyde; s2, adjusting the pH value of the first monomer glutaraldehyde solution to 5.0-9.0, soaking the biomedical material in the first monomer glutaraldehyde solution, keeping the temperature and keeping the biomedical material for a certain time; s3, adjusting the pH value of the first alcohol solution to 5.0-9.0, soaking the biomedical material obtained in the step S2 in the first alcohol solution, keeping the temperature and keeping the temperature for a certain time; s4, adjusting the pH value of the second monomer glutaraldehyde solution to 5.0-9.0, soaking the biomedical material obtained in the step S3 in the second monomer glutaraldehyde solution, keeping the temperature and keeping the temperature for a certain time; s5, adjusting the pH value of the third monomer glutaraldehyde solution to 5.0-9.0, soaking the biomedical material obtained in the step S4 in the third monomer glutaraldehyde solution, keeping the temperature and continuously storing to obtain the calcification-preventing biomedical material.)

1. A method of preventing calcification of a biomedical material, comprising:

s1, treating glutaraldehyde to obtain high-purity monomer glutaraldehyde;

s2, adjusting the pH value of the first monomer glutaraldehyde solution to 5.0-9.0, soaking the biomedical material in the first monomer glutaraldehyde solution, keeping the temperature and keeping the biomedical material for a certain time;

s3, adjusting the pH value of the first alcohol solution to 5.0-9.0, soaking the biomedical material obtained in the step S2 in the first alcohol solution, keeping the temperature and keeping the temperature for a certain time;

s4, adjusting the pH value of the second monomer glutaraldehyde solution to 5.0-9.0, soaking the biomedical material obtained in the step S3 in the second monomer glutaraldehyde solution, keeping the temperature and keeping the temperature for a certain time;

s5, adjusting the pH value of the third monomer glutaraldehyde solution to 5.0-9.0, soaking the biomedical material obtained in the step S4 in the third monomer glutaraldehyde solution, keeping the temperature and continuously storing to obtain the calcification-preventing biomedical material.

2. The method for preventing calcification of a biomedical material as claimed in claim 1, wherein the step S1 of treating glutaraldehyde specifically includes subjecting glutaraldehyde to gas membrane separation, reduced-pressure fractional distillation, and nanofiltration membrane separation, and removing polymeric substances of glutaraldehyde dimer, glutaraldehyde trimer, and glutaraldehyde tetramer in glutaraldehyde to obtain high-purity monomeric glutaraldehyde.

3. The method for preventing calcification of a biomedical material as claimed in claim 1, wherein said first monomeric glutaraldehyde solution in step S2 includes one or more of phosphoric acid buffer solution and glutaraldehyde; the concentration of the first monomer glutaraldehyde solution is 0.1% -2%; the pH of the first monomeric glutaraldehyde solution is adjusted to 7.1-7.8; the temperature of the first glutaraldehyde solution is adjusted to 3-50 ℃; the biomedical material is continuously soaked in the first glutaraldehyde solution for 4 hours to 10 days.

4. The method for preventing calcification of a biomedical material as claimed in claim 3, wherein the substance of the first alcohol solution in step S3 includes one or more of alcohol, phosphoric acid buffer solution, HEPES buffer solution; the alcohol comprises one or more of ethanol, n-propanol, isopropanol, n-butanol and isobutanol; the volume of the alcohol in the first alcohol solution accounts for 10-100%; the pH of the first alcohol solution is adjusted to 7.1-7.8; the temperature of the first alcohol solution is adjusted to 3-40 ℃; the biomedical material is continuously soaked in the first alcohol solution for 10 hours to 3 days.

5. The method for preventing calcification of a biomedical material as claimed in claim 4, wherein said second glutaraldehyde solution in step S4 includes one or more of phosphate buffer solution and glutaraldehyde; the concentration of the second glutaraldehyde is 0.05% -2%; the pH of the second glutaraldehyde solution is adjusted to 7.1-7.8; the temperature of the second glutaraldehyde solution is adjusted to 3-45 ℃; the biomedical material is continuously soaked in the second glutaraldehyde solution for 4 hours to 7 days.

6. The method for preventing calcification of a biomedical material as claimed in claim 5, wherein the substance of the third glutaraldehyde solution in step S5 includes one or more of phosphate buffer solution and glutaraldehyde; the concentration of the third glutaraldehyde is 0.1% -1%; the pH of the third glutaraldehyde solution is adjusted to 7.1-7.8; the temperature of the third glutaraldehyde solution is adjusted to 3-40 ℃; the biomedical material is continuously soaked in a third glutaraldehyde solution and stored for a long time.

7. The method of claim 6, wherein the first alcohol solution comprises 60% to 100% alcohol by volume.

8. The method of claim 1, wherein the biomedical material is mammalian tissue; the mammal tissue is one or more of pericardial tissue, valve tissue, vascular tissue, adventitia, pleura, peritoneum, achilles tendon, and ligament.

9. The method for preventing calcification of a biomedical material as claimed in claim 1, wherein said step S2 and/or step S3 and/or step S4 and/or step S5 are performed under non-oxidizing conditions, said non-oxidizing conditions including keying of antioxidants, inert gas shielding, dim light, for enhancing the performance of the biomedical material.

10. The method for preventing calcification of a biomedical material as claimed in claim 1, wherein an antioxidant is added to said first monomeric glutaraldehyde solution and/or said first alcohol solution and/or said second monomeric glutaraldehyde solution and/or said third monomeric glutaraldehyde solution, said antioxidant comprising ascorbic acid.

11. The method for preventing calcification of a biomedical material as claimed in claim 10, wherein one or more of formaldehyde, surfactant, ethanol and isopropanol are added to the first monomeric glutaraldehyde solution and/or the second monomeric glutaraldehyde solution and/or the third monomeric glutaraldehyde solution to improve the actual efficacy of the solution.

12. The method of claim 1, wherein the first alcohol solution comprises one or more of formaldehyde, a surfactant, glutaraldehyde, and isopropanol to improve the effective efficacy of the solution.

13. The method for preventing calcification of a biomedical material as claimed in claim 1, wherein a phosphoric acid buffer solution and/or a HEPES buffer solution is/are used in the preparation of the first glutaraldehyde solution, the first alcohol solution, the second glutaraldehyde solution and the third glutaraldehyde solution.

Technical Field

The invention relates to the technical field of medical methods, in particular to a method for preventing calcification of a biomedical material.

Background

Biomedical materials are used as a foundation for researching artificial organs and medical instruments, become important branches of modern material disciplines, and particularly become hot spots for research and development by competition among scientists of various countries along with the vigorous development and major breakthrough of biotechnology, and related reports of application and research of related medical materials and medical materials in the field of high and new medical technology are endless in recent years.

The biomedical materials are also called biological materials, the traditional fields mainly comprise artificial organs (orthopedic implants, artificial bones, artificial joints, artificial prostheses and the like) supporting the movement function, artificial organs (artificial blood vessels, artificial heart valves and the like) having the blood circulation function, artificial organs having the plastic and cosmetic functions, artificial organs having the sensory functions (artificial crystals, artificial cochlea and the like) and the like, and the novel fields mainly comprise molecular diagnosis, 3D printing and the like.

Although biomedical materials have been applied with great success, a lot of problems are exposed in long-term clinical application, and the outstanding effects are that the requirements of clinical application cannot be well met in terms of functionality, immunity, service life and the like. For example, the death rate of the heart valve reaches 58 percent after the heart valve is implanted for 12 years, the restenosis rate of the blood vessel reaches about 10 percent after the blood vessel stent is implanted, the validity period of the artificial joint is 12 to 15 years for the old group, and the middle-young group only reaches about 5 years. Among other things, calcification of the material seriously affects the functionality of the material. At present, the principle of the calcification rate of biomedical materials has not been fully studied. However, factors that are thought to affect the rate of calcification include the age of the patient, the presence of metabolic disturbances, dietary factors, the presence of infection, parenteral calcium administration, dehydration, in situ deformation of the bioprosthesis, inadequate anticoagulant therapy during the initial period of surgical implantation, and immune host-tissue response.

In recent years, much effort has been made to prevent calcification of biomedical materials. The technologies that have been harvested from these efforts can be broadly divided into two categories: it relates to the pre-or post-treatment of glutaraldehyde-fixed tissue with one or more compounds that inhibit calcification, as described in the literature: Carpentier-Edwards thermal Process A Method for extracting Calcium Binding Sites from Perical Tissue and involves fixing the Tissue with a compound other than glutaraldehyde, thereby reducing calcification.

The biological valve material is generally tanned and preserved by glutaraldehyde, glutaraldehyde can increase the thermal shrinkage temperature and mechanical tensile strength of tissues and reduce immunogenicity, but free aldehyde groups have a cytotoxic effect and reduce calcium-dependent ATPase activity on cell membranes, so that the calcium content in cells is increased, and tissues are calcified.

Although some of these techniques have proven effective in reducing material calcification, there remains a need in the art for further improvements to the prior art or for the development of new anti-calcification techniques.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provides a method for preventing calcification of a biomedical material.

In order to achieve the purpose, the invention adopts the following technical scheme:

a method of preventing calcification of a biomedical material, comprising:

s1, treating glutaraldehyde to obtain high-purity monomer glutaraldehyde;

s2, adjusting the pH value of the first monomer glutaraldehyde solution to 5.0-9.0, soaking the biomedical material in the first monomer glutaraldehyde solution, keeping the temperature and keeping the biomedical material for a certain time;

s3, adjusting the pH value of the first alcohol solution to 5.0-9.0, soaking the biomedical material obtained in the step S2 in the first alcohol solution, keeping the temperature and keeping the temperature for a certain time;

s4, adjusting the pH value of the second monomer glutaraldehyde solution to 5.0-9.0, soaking the biomedical material obtained in the step S3 in the second monomer glutaraldehyde solution, keeping the temperature and keeping the temperature for a certain time;

s5, adjusting the pH value of the third monomer glutaraldehyde solution to 5.0-9.0, soaking the biomedical material obtained in the step S4 in the third monomer glutaraldehyde solution, keeping the temperature and continuously storing to obtain the calcification-preventing biomedical material.

Further, the step S1 of treating glutaraldehyde specifically includes subjecting glutaraldehyde to gas membrane separation, reduced-pressure fractional distillation, and nanofiltration membrane separation, to remove polymeric substances of glutaraldehyde dimer, glutaraldehyde trimer, and glutaraldehyde tetramer in glutaraldehyde, and obtain high-purity monomeric glutaraldehyde.

Further, the first monomer glutaraldehyde solution in step S2 includes one or more of phosphoric acid buffer solution and glutaraldehyde; the concentration of the first monomer glutaraldehyde solution is 0.1% -2%; the pH of the first monomeric glutaraldehyde solution is adjusted to 7.1-7.8; the temperature of the first glutaraldehyde solution is adjusted to 3-50 ℃; the biomedical material is continuously soaked in the first glutaraldehyde solution for 4 hours to 10 days.

Further, the substance of the first alcohol solution in step S3 includes one or more of alcohols, phosphoric acid buffer solution, HEPES buffer solution; the alcohol comprises one or more of ethanol, n-propanol, isopropanol, n-butanol and isobutanol; the volume of the alcohol in the first alcohol solution accounts for 10-100%; the pH of the first alcohol solution is adjusted to 7.1-7.8; the temperature of the first alcohol solution is adjusted to 3-40 ℃; the biomedical material is continuously soaked in the first alcohol solution for 10 hours to 3 days.

Further, the second glutaraldehyde solution in step S4 includes one or more of a phosphate buffer solution and glutaraldehyde; the concentration of the second glutaraldehyde is 0.05% -2%; the pH of the second glutaraldehyde solution is adjusted to 7.1-7.8; the temperature of the second glutaraldehyde solution is adjusted to 3-45 ℃; the biomedical material is continuously soaked in the second glutaraldehyde solution for 4 hours to 7 days.

Further, the third glutaraldehyde solution in step S5 includes one or more of a phosphate buffer solution and glutaraldehyde; the concentration of the third glutaraldehyde is 0.1% -1%; the pH of the third glutaraldehyde solution is adjusted to 7.1-7.8; the temperature of the third glutaraldehyde solution is adjusted to 3-40 ℃; the biomedical material is continuously soaked in a third glutaraldehyde solution and stored for a long time.

Further, the volume of the alcohol in the first alcohol solution is 60-100%.

Further, the biomedical material is mammalian tissue; the mammal tissue is one or more of pericardial tissue, valve tissue, vascular tissue, adventitia, pleura, peritoneum, achilles tendon, and ligament.

Further, the step S2 and/or the step S3 and/or the step S4 and/or the step S5 are performed under non-oxidizing conditions including keying of an antioxidant, inert gas shielding, dark light for enhancing the performance of the biomedical material.

Further, an antioxidant is added into the first monomer glutaraldehyde solution and/or the first alcohol solution and/or the second monomer glutaraldehyde solution and/or the third monomer glutaraldehyde solution, and the antioxidant comprises ascorbic acid.

Furthermore, one or more of formaldehyde, a surfactant, ethanol and isopropanol are added into the first monomer glutaraldehyde solution and/or the second monomer glutaraldehyde solution and/or the third monomer glutaraldehyde solution so as to improve the practical efficacy of the solution.

Further, one or more of formaldehyde, a surfactant, glutaraldehyde and isopropanol are included in the first alcohol solution to improve the practical efficacy of the solution.

Furthermore, phosphoric acid buffer solution and/or HEPES buffer solution are/is adopted when the first monomer glutaraldehyde solution, the first alcohol solution, the second monomer glutaraldehyde solution and the third monomer glutaraldehyde solution are prepared.

Compared with the prior art, the glutaraldehyde adopted by the invention is high-purity monomer glutaraldehyde which is obtained by removing polymer substances such as glutaraldehyde dimers, glutaraldehyde trimers, glutaraldehyde tetramers and the like through gas membrane separation, reduced-pressure fractional distillation and nanofiltration membrane separation. The biomedical material is cross-linked by monomer glutaraldehyde with a certain concentration, then is processed by alcohol, and is stored in monomer glutaraldehyde solution after sterilization. Thereby obtaining the biomedical material with excellent calcification-preventing effect.

Drawings

Fig. 1 is a flowchart of a method for preventing calcification of a biomedical material according to an embodiment.

Detailed Description

The embodiments of the present invention are described below with reference to specific embodiments, and other advantages and effects of the present invention will be easily understood by those skilled in the art from the disclosure of the present specification. The invention is capable of other and different embodiments and of being practiced or of being carried out in various ways, and its several details are capable of modification in various respects, all without departing from the spirit and scope of the present invention. It is to be noted that the features in the following embodiments and examples may be combined with each other without conflict.

The invention aims to provide a method for preventing calcification of biomedical materials, aiming at the defects of the prior art.