Regenerative medical material for promoting tissue in-situ regeneration and preparation method thereof
阅读说明：本技术 一种促进组织原位再生的再生医学材料及其制备方法 (Regenerative medical material for promoting tissue in-situ regeneration and preparation method thereof ) 是由 曹小伍 雷铭轩 于 2020-04-15 设计创作，主要内容包括：本发明公开了一种促进组织原位再生的再生医学材料及其制备方法,属于生物医药技术领域,由如下对应重量份的物质组成：85～90份聚乙二醇、4～10份甘油、1～2份医用级维生素E油、20～25份再生增强材料、2～4份葡萄糖酸内酯。本发明再生医学材料对人体组织的刺激性小,促进组织再生恢复能力强,成分简单、制造方便。(The invention discloses a regenerative medical material for promoting tissue in-situ regeneration and a preparation method thereof, belonging to the technical field of biological medicine and consisting of the following substances in parts by weight: 85-90 parts of polyethylene glycol, 4-10 parts of glycerol, 1-2 parts of medical-grade vitamin E oil, 20-25 parts of a regeneration reinforcing material and 2-4 parts of gluconolactone. The regenerative medical material has the advantages of small irritation to human tissues, strong capability of promoting tissue regeneration and recovery, simple components and convenient manufacture.)
1. A regenerative medical material for promoting tissue in-situ regeneration is characterized by comprising the following substances in parts by weight: 85-90 parts of polyethylene glycol, 4-10 parts of glycerol, 1-2 parts of medical-grade vitamin E oil, 20-25 parts of a regeneration reinforcing material and 2-4 parts of gluconolactone.
2. The regenerative medical material for promoting tissue in-situ regeneration according to claim 1, which is prepared from the following substances in parts by weight: 88 parts of polyethylene glycol, 7 parts of glycerol, 1.5 parts of medical-grade vitamin E oil, 23 parts of a regeneration enhancing material and 3 parts of gluconolactone.
3. The regenerative medical material for promoting tissue in-situ regeneration as claimed in claim 1, wherein the polyethylene glycol is prepared by mixing polyethylene glycol 400 and polyethylene glycol 4000 according to a weight ratio of 4-6: 1.
4. The regenerative medical material for promoting tissue regeneration in situ according to claim 1, wherein the preparation method of the regenerative reinforcing material comprises the following steps:
(1) immersing the bioactive glass powder particles into the composite liquid A, then adding a calcium chloride solution into the composite liquid A, continuously stirring for 45-50 min, and filtering out for later use;
(2) mixing polycaprolactone, degradable aliphatic polyester and an organic solvent together, and uniformly stirring by magnetic force to obtain a mixed solution B for later use;
(3) putting the bioactive glass powder particles treated in the step (1) into the mixed liquid B obtained in the step (2), and performing ultrasonic treatment for 1.5-2 hours to obtain mixed liquid C for later use;
(4) and (4) carrying out electrostatic spinning treatment on the mixed solution C obtained in the step (3) to obtain a spinning membrane, then crushing the spinning membrane, and finally drying and disinfecting to obtain the regenerated reinforced material.
5. A regenerative medical material for promoting tissue regeneration in situ as claimed in claim 4, wherein the bioactive glass powder particles in step (1) are composed of the following materials in parts by weight: 12 to 16 parts of P2O550-55 parts of SiO24-8 parts of Na2O, 15-20 parts of CaO; the bioactive glass powder particles are subjected to particle size classification treatment, wherein the particle size isThe particles with the particle size of 25-30 mu m account for 50-55 percent of the total weight, the particles with the particle size of 1-5 mu m account for 30-35 percent of the total weight, and the particles with the particle size of 300-400 nm account for the rest.
6. The regenerative medical material for promoting tissue in-situ regeneration according to claim 4, wherein the composite liquid A in step (1) is prepared from the following substances in parts by weight: 3-6 parts of nano chitin, 5-10 parts of sodium alginate, 1-3 parts of gelatin, 0.1-0.2 part of antibacterial agent and 120-140 parts of deionized water; the adding amount of the calcium chloride solution is 4-7% of the total mass of the composite liquid A, and the mass fraction of the calcium chloride solution is 2-3%.
7. The regenerative medical material for promoting tissue in-situ regeneration according to claim 4, wherein the weight volume ratio of the polycaprolactone, the degradable aliphatic polyester and the organic solvent in step (2) is as follows: 10-15 g: 6-10 g: 90-100 mL; the organic solvent is any one of trifluoroethanol, trichloromethane and methanol.
8. The regenerative medical material for promoting tissue in-situ regeneration as claimed in claim 4, wherein the weight ratio of the bioactive glass powder particles to the mixed solution B in the step (3) is 1: 9-10; and controlling the frequency of the ultrasonic wave to be 500-550 kHz during ultrasonic treatment.
9. The regenerative medical material for promoting tissue in-situ regeneration according to claim 4, wherein the stainless steel roller is used as a receiving device during the electrostatic spinning treatment in the step (4), the rotating speed of the roller is controlled to be 700-740 rpm, the flow rate of the spinning solution is 7-9 mL/h, the voltage is 16-18 kV, the receiving distance is 20-25 cm, the spinning time is 10-12 h, and the thickness of the formed film is 60-100 μm; the diameter of flaky particles of the spinning film is controlled to be not more than 3mm after the spinning film is crushed.
10. A method for preparing a regenerative medical material for promoting tissue regeneration in situ according to claim 1, comprising the steps of:
firstly, putting polyethylene glycol and glycerol into a container together, heating to keep the temperature in the container at 65-70 ℃, and continuously stirring for 10-15 min;
and (II) adding medical-grade vitamin E oil, a regeneration enhancing material and gluconolactone into the container, heating the temperature in the container to 75-80 ℃, carrying out ultrasonic treatment for 1-1.5 h at 700-800 kHz, taking out, and naturally cooling to room temperature.
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to a regenerative medical material for promoting tissue in-situ regeneration and a preparation method thereof.
Background
At present, most medical dressings for promoting tissue regeneration are dressings containing bioactive glass, the bioactive glass has good bioactivity and biocompatibility, can activate expression of genes related to wound healing, promote proliferation and differentiation of fibroblasts, accelerate angiogenesis, promote growth of granulation tissues, promote repair and regeneration of hard tissues and soft tissues and promote healing of wounds, but after the dressings containing the bioactive glass are applied to wound surfaces, when bioactive glass particles are contacted with liquid, rapid reaction occurs on the surfaces of the dressings, local PH values are rapidly increased, the PH values can reach 13, strong basicity is formed, certain cytotoxicity is achieved, a lot of patients can cause instant severe pain due to stimulation, and certain pain is brought to the patients in the using process. And natural wound repair is a dynamic process involving multiple cellular and biological signals, which can be roughly divided into four phases, a hemostasis phase, an inflammation phase, a cell proliferation phase (or tissue formation phase), and a tissue remodeling phase. Although the repair of tissue wounds by means of common dressings and the like is advanced to a certain extent, most of the repair methods can only meet specific repair stages, and a good scheme meeting the wound repair rule is rarely provided.
Disclosure of Invention
The invention provides a regenerative medical material for promoting tissue in-situ regeneration and a preparation method thereof aiming at the problems brought forward by the background technology, can realize the in-situ regeneration and repair of wound tissues, can relieve the pain of patients in the using process and conforms to the rule of wound repair.
The invention is realized by the following technical scheme:
a regenerative medical material for promoting tissue in-situ regeneration is composed of the following substances in parts by weight: 85-90 parts of polyethylene glycol, 4-10 parts of glycerol, 1-2 parts of medical-grade vitamin E oil, 20-25 parts of a regeneration reinforcing material and 2-4 parts of gluconolactone.
Preferably, the composition consists of the following substances in parts by weight: 88 parts of polyethylene glycol, 7 parts of glycerol, 1.5 parts of medical-grade vitamin E oil, 23 parts of a regeneration enhancing material and 3 parts of gluconolactone.
Further, the polyethylene glycol is prepared by correspondingly mixing polyethylene glycol 400 and polyethylene glycol 4000 according to a weight ratio of 4-6: 1.
Further, the preparation method of the regenerated reinforcing material comprises the following steps:
(1) immersing the bioactive glass powder particles into the composite liquid A, then adding a calcium chloride solution into the composite liquid A, continuously stirring for 45-50 min, and filtering out for later use;
(2) mixing polycaprolactone, degradable aliphatic polyester and an organic solvent together, and uniformly stirring by magnetic force to obtain a mixed solution B for later use;
(3) putting the bioactive glass powder particles treated in the step (1) into the mixed liquid B obtained in the step (2), and performing ultrasonic treatment for 1.5-2 hours to obtain mixed liquid C for later use;
(4) and (4) carrying out electrostatic spinning treatment on the mixed solution C obtained in the step (3) to obtain a spinning membrane, then crushing the spinning membrane, and finally drying and disinfecting to obtain the regenerated reinforced material.
Further, the bioactive glass powder particles in the step (1) are composed of the following substances in parts by weight: 12 to 16 parts of P2O550-55 parts of SiO24-8 parts of Na2O, 15-20 parts of CaO; the bioactive glass powder particles are subjected to particle size grading treatment, wherein the particles with the particle size of 25-30 mu m account for 50-55% of the total weight, the particles with the particle size of 1-5 mu m account for 30-35% of the total weight, and the particles with the particle size of 300-400 nm account for the balance.
Further, the compound liquid A in the step (1) is composed of the following substances in parts by weight: 3-6 parts of nano chitin, 5-10 parts of sodium alginate, 1-3 parts of gelatin, 0.1-0.2 part of antibacterial agent and 120-140 parts of deionized water; the adding amount of the calcium chloride solution is 4-7% of the total mass of the composite liquid A, and the mass fraction of the calcium chloride solution is 2-3%.
Further, the weight-volume ratio of the polycaprolactone, the degradable aliphatic polyester and the organic solvent in the step (2) is as follows: 10-15 g: 6-10 g: 90-100 mL; the organic solvent is any one of trifluoroethanol, trichloromethane and methanol.
Further, the weight ratio of the bioactive glass powder particles to the mixed liquor B in the step (3) is 1: 9-10; and controlling the frequency of the ultrasonic wave to be 500-550 kHz during ultrasonic treatment.
Further, during the electrostatic spinning treatment in the step (4), a stainless steel roller is used as a receiving device, the rotating speed of the roller is controlled to be 700-740 revolutions per minute, the flow rate of the spinning solution is 7-9 mL/h, the voltage is 16-18 kV, the receiving distance is 20-25 cm, the spinning time is 10-12 h, and the thickness of a formed film is 60-100 mu m; the diameter of flaky particles of the spinning film is controlled to be not more than 3mm after the spinning film is crushed.
A method for preparing a regenerative medical material for promoting tissue regeneration in situ according to claim 1, comprising the steps of:
firstly, putting polyethylene glycol and glycerol into a container together, heating to keep the temperature in the container at 65-70 ℃, and continuously stirring for 10-15 min;
and (II) adding medical-grade vitamin E oil, a regeneration enhancing material and gluconolactone into the container, heating the temperature in the container to 75-80 ℃, carrying out ultrasonic treatment for 1-1.5 h at 700-800 kHz, taking out, and naturally cooling to room temperature.
Compared with the prior art, the invention has the beneficial effects that:
the invention provides a regenerative medical material, which is different from the existing material, the invention optimizes and improves the raw material components and the dosage of the compatibility, on the basis of the main materials of polyethylene glycol, glycerol and medical-grade vitamin E oil, the regenerative reinforcing material and the gluconolactone component are also added, wherein, the regenerative reinforcing material is a spinning membrane particle with high biological activity, the main component of the spinning membrane particle is processed by polycaprolactone and degradable aliphatic polyester as main film forming substances, the regenerative reinforcing material has good biological compatibility and degradation performance, can effectively prevent the growth of fibroblast and the like to the tissue defect, simultaneously promotes the regeneration and repair of the tissue, optimizes the process and the rule of the repair, and then adds the biological activity glass powder particles after special treatment, the biological activity glass powder particles have good antibacterial and bacteriostatic properties after being treated by the compound liquid A, the dispersion compatibility of the composite material is improved, and the composite material can be effectively distributed in tissues by matching with self particle grading and carrying of a spinning film, so that the effect of guiding the ordered crawling substitution of the tissues such as cells, extracellular matrixes, blood vessels and the like is improved, and the overall repairing effect is enhanced. The regenerative medical material has the advantages of small irritation to human tissues, strong capability of promoting tissue regeneration and recovery, simple components, convenient manufacture and contribution to popularization and application.
Detailed Description
The technical solutions in the embodiments of the present invention are clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. The specific embodiments described herein are merely illustrative of the invention and do not delimit the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
A regenerative medical material for promoting tissue in-situ regeneration is composed of the following substances in parts by weight: 85-90 parts of polyethylene glycol, 4-10 parts of glycerol, 1-2 parts of medical-grade vitamin E oil, 20-25 parts of a regeneration reinforcing material and 2-4 parts of gluconolactone.
The polyethylene glycol is prepared by correspondingly mixing polyethylene glycol 400 and polyethylene glycol 4000 according to the weight ratio of 4-6: 1.
The preparation method of the regenerated reinforcing material comprises the following steps:
(1) immersing the bioactive glass powder particles into the composite liquid A, then adding a calcium chloride solution into the composite liquid A, continuously stirring for 45-50 min, and filtering out for later use;
(2) mixing polycaprolactone, degradable aliphatic polyester and an organic solvent together, and uniformly stirring by magnetic force to obtain a mixed solution B for later use;
(3) putting the bioactive glass powder particles treated in the step (1) into the mixed liquid B obtained in the step (2), and performing ultrasonic treatment for 1.5-2 hours to obtain mixed liquid C for later use;
(4) and (4) carrying out electrostatic spinning treatment on the mixed solution C obtained in the step (3) to obtain a spinning membrane, then crushing the spinning membrane, and finally drying and disinfecting to obtain the regenerated reinforced material.
The bioactive glass powder particles in the step (1) are composed of the following substances in parts by weight: 12 to 16 parts of P2O550-55 parts of SiO24-8 parts of Na2O, 15-20 parts of CaO; the bioactive glass powder particles are subjected to particle size grading treatment, wherein the particles with the particle size of 25-30 mu m account for 50-55% of the total weight, the particles with the particle size of 1-5 mu m account for 30-35% of the total weight, and the particles with the particle size of 300-400 nm account for the balance.
The compound liquid A in the step (1) is composed of the following substances in parts by weight: 3-6 parts of nano chitin, 5-10 parts of sodium alginate, 1-3 parts of gelatin, 0.1-0.2 part of antibacterial agent and 120-140 parts of deionized water; the adding amount of the calcium chloride solution is 4-7% of the total mass of the composite liquid A, and the mass fraction of the calcium chloride solution is 2-3%.
The polycaprolactone, the degradable aliphatic polyester and the organic solvent in the step (2) correspond to the following weight-volume ratio: 10-15 g: 6-10 g: 90-100 mL; the organic solvent is any one of trifluoroethanol, trichloromethane and methanol.
The weight ratio of the bioactive glass powder particles to the mixed liquid B in the step (3) is 1: 9-10; and controlling the frequency of the ultrasonic wave to be 500-550 kHz during ultrasonic treatment.
During the electrostatic spinning treatment in the step (4), a stainless steel roller is used as a receiving device, the rotating speed of the roller is controlled to be 700-740 revolutions per minute, the flow rate of a spinning solution is 7-9 mL/h, the voltage is 16-18 kV, the receiving distance is 20-25 cm, the spinning time is 10-12 h, and the thickness of a formed film is 60-100 mu m; the diameter of flaky particles of the spinning film is controlled to be not more than 3mm after the spinning film is crushed.
A method for preparing a regenerative medical material for promoting tissue regeneration in situ according to claim 1, comprising the steps of:
firstly, putting polyethylene glycol and glycerol into a container together, heating to keep the temperature in the container at 65-70 ℃, and continuously stirring for 10-15 min;
and (II) adding medical-grade vitamin E oil, a regeneration enhancing material and gluconolactone into the container, heating the temperature in the container to 75-80 ℃, carrying out ultrasonic treatment for 1-1.5 h at 700-800 kHz, taking out, and naturally cooling to room temperature.