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CN110680832B - Wound tissue self-derived regeneration and repair ointment and preparation method thereof - Google Patents

Wound tissue self-derived regeneration and repair ointment and preparation method thereof
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Publication number
CN110680832B
CN110680832BCN201810722993.1ACN201810722993ACN110680832BCN 110680832 BCN110680832 BCN 110680832BCN 201810722993 ACN201810722993 ACN 201810722993ACN 110680832 BCN110680832 BCN 110680832B
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polyethylene glycol
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CN110680832A (en
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王菲
高玉森
胡方
郭创洲
王健
张芷铭
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Beijing Best Life Regenerative Medicine Technology Co ltd
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Beijing Xingfu Yisheng High Tech Co ltd
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Abstract

Translated fromChinese

一种创面组织自源性再生修复软膏,其特征在于,是由以下重量份的原料组成:再生医学材料10‑40份、聚乙二醇4000 5‑20份、聚乙二醇400 30‑80份、甘油5‑25份、医用级维生素E油0.5‑3份,通过将再生医学材料、聚乙二醇、甘油和医用级维生素E油采用特定方式进行配比混合,可以使其达到引导细胞、细胞外基质、血管等组织有序爬行替代的作用,促进伤口愈合加速,对创面的神经系统同步进行修复,实现新生组织纤维层有序生长,毛细血管、毛囊再生,实现创伤内源性组织再生修复,抑制疤痕形成,同时,该混合物的PH值为7.3‑7.8,比较接近人体的PH值,在使用过程中对人体的刺激性小,从而减轻患者的痛苦。A wound tissue autogenous regeneration repair ointment, which is characterized in that it is composed of the following raw materials in parts by weight: 10-40 parts of regenerative medicine materials, 5-20 parts of polyethylene glycol, 400-30-80 parts of polyethylene glycol parts, 5-25 parts of glycerol, and 0.5-3 parts of medical-grade vitamin E oil. By mixing regenerative medicine materials, polyethylene glycol, glycerin, and medical-grade vitamin E oil in a specific way, they can guide cells , The role of extracellular matrix, blood vessels and other tissues in orderly crawling and replacement, promote wound healing and accelerate wound healing, repair the nervous system of the wound synchronously, realize the orderly growth of the new tissue fiber layer, regenerate capillaries and hair follicles, and realize the wound endogenous tissue. Regenerate and repair, and inhibit scar formation. At the same time, the pH value of the mixture is 7.3-7.8, which is relatively close to the pH value of the human body, and it is less irritating to the human body during use, thereby reducing the pain of patients.

Description

Wound tissue self-derived regeneration and repair ointment and preparation method thereof
Technical Field
The invention relates to the technical field of external medicines, in particular to wound tissue self-induced regeneration and repair ointment and a preparation method thereof.
Background
At present, most medical dressings are dressings containing bioactive glass, the bioactive glass has good bioactivity and biocompatibility, and 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 bioactive glass particles, so that local pH value is rapidly increased, the pH value can reach 13, strong alkalinity is formed, certain cytotoxicity is realized, a lot of patients can cause instant severe pain due to stimulation, and certain pain is brought to the patients in the using process.
Disclosure of Invention
The invention provides wound tissue self-induced regeneration and repair ointment and a preparation method thereof, aims to solve the problems in the prior art, and provides wound tissue self-induced regeneration and repair ointment which is beneficial to rapid wound healing, realizes wound endogenous tissue regeneration and repair and can relieve the pain of a patient in the using process and a preparation method thereof.
The technical scheme adopted by the invention for solving the problems is as follows:
the wound tissue self-induced regeneration repair ointment is characterized by comprising the following raw materials in parts by weight: 10-40 parts of regenerative medicine material, 05-20 parts of polyethylene glycol 40005, 30-80 parts of polyethylene glycol 4005-25 parts of glycerol and 0.5-3 parts of medical vitamin E oil.
The regenerative medical material comprises the following components in parts by weight: p2O510-25 parts of SiO220-60 parts of Na2O2-20 parts and CaO 15-45 parts.
90% of the regenerative medical material has a particle size of less than 50 μm.
The particle size of 60-90% of the regenerative medical material is less than 30 μm.
A preparation method of wound tissue self-induced regeneration repair ointment is characterized by comprising the following steps:
(1) putting polyethylene glycol 400 and polyethylene glycol 4000 into a container, heating to 75 ℃ to melt, and stirring for 10-20min at the same time until the polyethylene glycol 400 and the polyethylene glycol 4000 are uniformly mixed to prepare a solution A;
(2) adding glycerol into the solution A, stirring at 75 deg.C for 20-30min, and mixing glycerol and the solution A to obtain solution B;
(3) adding the regenerated medical material into the solution B for a certain number of times, stirring for 60-90min at 75 ℃, and uniformly mixing the regenerated medical material and the solution B to prepare a solution C;
(4) adding medical-grade vitamin E oil into the solution C, continuously stirring at 75 ℃ for 40-70min, and uniformly mixing the medical-grade vitamin E oil and the solution C to prepare a solution D;
(5) and continuously and uniformly stirring the solution D until the temperature is reduced to the room temperature, thus completing the preparation.
The regenerative medical material was added to solution B in equal amounts in four times.
The pH value of the wound tissue self-induced regeneration repair ointment prepared by the preparation method is 7.3-7.8.
The invention has the beneficial effects that: the regenerative medical material, the polyethylene glycol, the glycerol and the medical vitamin E oil are mixed in a specific mode, so that the effect of guiding the tissues such as cells, extracellular matrixes and blood vessels to climb and replace orderly can be achieved, the wound healing is accelerated, the nervous system of a wound surface is synchronously repaired, the fibrous layer of the regenerated tissue grows orderly, the blood capillaries and the hair follicles are regenerated, the regeneration and repair of the endogenous tissues of the wound are realized, the scar formation is inhibited, meanwhile, the pH value of the mixture is 7.3-7.8 and is relatively close to that of a human body, the irritation to the human body is small in the using process, and the pain of a patient is relieved.
Detailed Description
For a further understanding of the invention, reference will now be made to the following examples, which are included to provide a further understanding of the invention, and are intended to be purely exemplary of the invention, rather than to be exhaustive of the invention.
A wound surface tissue self-induced regeneration repair ointment is composed of the following raw materials in parts by weight: 10-40 parts of regenerative medicine material, 05-20 parts of polyethylene glycol 40005, 30-80 parts of polyethylene glycol 4005-25 parts of glycerol and 0.5-3 parts of medical vitamin E oil, and the components are prepared into the formulaThe regenerative medical material comprises the following components in parts by weight: p2O510-25 parts of SiO220-60 parts of Na2O2-20 parts and CaO 15-45 parts.
90% of the regenerative medical material has the particle size smaller than 50 mu m, the regenerative medical material has large specific surface area and high reaction speed, and can obtain quick treatment effect.
The regenerative medical material has the particle size of more than 60% and less than 90% and less than 30 μm, has large specific surface area and high reaction speed, and can obtain rapid treatment effect.
In the formula of the ointment:
calcium ions and phosphorus ions in the regenerative medical material are uniformly distributed in a three-dimensional network structure with reordered silicon bonds, the degradation speed of the product in vivo is regulated and controlled by regulating the content of phosphorus, the complete creeping substitution of the new tissue is solved, and the comprehensive repair and regeneration of the new tissue from the shape, the structure and the function are realized.
Polyethylene glycol 40005-20 parts, polyethylene glycol 400 polymer polyethylene glycol is adsorbed on the surface of the regenerative medicine material particles, and the surface of the regenerative medicine material does not react, so that the product has good stability during storage and does not lose the treatment effect.
The glycerol has synergistic effect, and has effects of promoting absorption of skin nervous system and healing wound tissue.
The medical vitamin E oil has good moisture retention and repair components, and can enable the regenerative medical material to better play the roles of wound healing, repair and regeneration.
A preparation method of wound tissue self-induced regeneration repair ointment comprises the following steps:
(1) putting polyethylene glycol 400 and polyethylene glycol 4000 into a container, heating to 75 ℃ to melt, and stirring for 10-20min at the same time until the polyethylene glycol 400 and the polyethylene glycol 4000 are uniformly mixed to prepare a solution A;
(2) adding glycerol into the solution A, stirring at 75 deg.C for 20-30min, and mixing glycerol and the solution A to obtain solution B;
(3) adding the regenerated medical material into the solution B for a certain number of times, stirring for 60-90min at 75 ℃, and uniformly mixing the regenerated medical material and the solution B to prepare a solution C;
(4) adding medical-grade vitamin E oil into the solution C, continuously stirring at 75 ℃ for 40-70min, and uniformly mixing the medical-grade vitamin E oil and the solution C to prepare a solution D;
(5) and continuously and uniformly stirring the solution D until the temperature is reduced to the room temperature, thus completing the preparation.
The regenerative medical material was added to solution B in equal amounts in four times.
The pH value of the wound tissue self-induced regeneration repair ointment prepared by the preparation method is 7.3-7.8.
By adjusting the proportion and the preparation method among the regenerative medical materials, the polyethylene glycol 400, the polyethylene glycol 4000, the glycerol and the medical-grade vitamin E oil, the pH value of the ointment is 7.3-7.8, when the ointment is used, the regenerative medical materials are in contact with cell body fluid, the pH value is stabilized at about 7.4, and the similar materials can be remarkably reduced, such as: the surface reactions of particles such as bioactive glass, silicon sodium calcium phosphate and the like enable the PH to rise, and the skin tissue is stimulated to pain and brings adverse effects to new cells caused by strong alkalinity, and the adhesion and proliferation of the new cells are facilitated, and the formation of the skin new tissues is facilitated.
The regenerative medical material can realize ion exchange in cells, calcium ions and phosphorus ions in the regenerative medical material are uniformly distributed in a three-dimensional network structure with silicon bonds rearranged to form a three-dimensional network structure consistent with the original skin, OH-negative charge ions generated in the regenerative medical material form a human skin growth machine block by adsorbing growth factors in a large number of cells, are attached to the three-dimensional network structure, crawl to replace the original cells, grow new cells, realize cell proliferation and accelerate skin regeneration.
The regenerative medical material can adsorb and remove wound necrotic tissues at the same time, generate a hydroxyapatite film with bioactivity, maintain the wound healing environment, and play roles in stopping bleeding and resisting inflammation; the wound healing promoting agent can also guide ordered creeping substitution of cells, extracellular matrixes, blood vessels and the like, promote wound healing to be accelerated, synchronously repair a nervous system of a wound surface, realize ordered growth of a fiber layer of a new tissue, regeneration of capillaries and hair follicles, regeneration and repair of endogenous tissues of the wound, and inhibit scar formation.
The wound tissue self-derived regeneration repair ointment has the advantages that the particle size of 90% of powder in the regenerative medical material is smaller than 50 mu m, the particle size of more than 60% of powder is smaller than 30 mu m, the specific surface area of the regenerative medical material is large, the reaction speed is high, and the rapid treatment effect can be obtained.
Example 1
A wound surface tissue self-induced regeneration repair ointment is composed of the following raw materials in parts by weight: 10 parts of regenerative medicine material, 05 parts of polyethylene glycol 40030 parts of polyethylene glycol 400, 5 parts of glycerol and 0.5 part of medical-grade vitamin E oil, wherein each part of the regenerative medicine material comprises the following components: p2O510-25 parts of SiO220-60 parts of Na2O2-20 parts and CaO 15-45 parts.
The preparation method comprises the following steps:
(1) putting 30 parts of polyethylene glycol 400 and 5 parts of polyethylene glycol 4000 into a container, heating to 75 ℃ to melt, and stirring for 10-20min at the same time until the polyethylene glycol 400 and the polyethylene glycol 4000 are uniformly mixed to prepare a solution A;
(2) adding 5 parts of glycerol into the solution A, stirring at 75 ℃ for 20-30min, and uniformly mixing the glycerol and the solution A to prepare a solution B;
(3) dividing 10 parts of regenerative medical materials into four parts, adding the four parts of regenerative medical materials into the solution B, stirring for 60-90min at 75 ℃, wherein the time interval between adjacent addition of the regenerative medical materials is 6-8min, and uniformly mixing the regenerative medical materials with the solution B to prepare solution C;
(4) adding 0.5 part of medical-grade vitamin E oil into the solution C, continuously stirring for 40-70min at 75 ℃, and uniformly mixing the medical-grade vitamin E oil and the solution C to prepare a solution D;
(5) and continuously and uniformly stirring the solution D until the temperature is reduced to the room temperature, thus completing the preparation.
Example 2
Wound surface tissue self-regeneration repair soft tissueThe paste consists of the following raw materials in parts by weight: 40 parts of regenerative medicine material, 400020 parts of polyethylene glycol, 40080 parts of polyethylene glycol, 25 parts of glycerol and 3 parts of medical-grade vitamin E oil, wherein each part of the regenerative medicine material comprises the following components: p2O510-25 parts of SiO220-60 parts of Na2O2-20 parts and CaO 15-45 parts.
The preparation method comprises the following steps:
(1) putting 80 parts of polyethylene glycol 400 and 20 parts of polyethylene glycol 4000 into a container, heating to 75 ℃ to melt, and stirring for 10-20min at the same time until the polyethylene glycol 400 and the polyethylene glycol 4000 are uniformly mixed to prepare a solution A;
(2) adding 25 parts of glycerol into the solution A, stirring at 75 ℃ for 20-30min, and uniformly mixing the glycerol and the solution A to prepare a solution B;
(3) dividing 40 parts of regenerative medical materials into four parts, adding into the solution B in four times, stirring at 75 ℃ for 60-90min, wherein the time interval between adjacent addition of the regenerative medical materials is 6-8min, and uniformly mixing the regenerative medical materials with the solution B to prepare solution C;
(4) adding 3 parts of medical-grade vitamin E oil into the solution C, continuously stirring for 40-70min at 75 ℃, and uniformly mixing the medical-grade vitamin E oil and the solution C to prepare a solution D;
(5) and continuously and uniformly stirring the solution D until the temperature is reduced to the room temperature, thus completing the preparation. .
Example 3
A wound surface tissue self-induced regeneration repair ointment is composed of the following raw materials in parts by weight: 25 parts of regenerative medicine material, 400012.5 parts of polyethylene glycol, 40055 parts of polyethylene glycol, 12.5 parts of glycerol and 1.5 parts of medical vitamin E oil, wherein each part of the regenerative medicine material comprises the following components: p2O510-25 parts of SiO220-60 parts of Na2O2-20 parts and CaO 15-45 parts.
The preparation method comprises the following steps:
(1) putting 55 parts of polyethylene glycol 400 and 12.5 parts of polyethylene glycol 4000 into a container, heating to 75 ℃ to melt, and stirring for 10-20min at the same time until the polyethylene glycol 400 and the polyethylene glycol 4000 are uniformly mixed to prepare a solution A;
(2) adding 12.5 parts of glycerol into the solution A, stirring at 75 ℃ for 20-30min, and uniformly mixing the glycerol and the solution A to prepare a solution B;
(3) equally dividing 25 parts of regenerative medical materials into four parts, adding the four parts of regenerative medical materials into the solution B, stirring for 60-90min at 75 ℃, wherein the time interval between adjacent addition of the regenerative medical materials is 6-8min, and uniformly mixing the regenerative medical materials with the solution B to prepare solution C;
(4) adding 1.5 parts of medical-grade vitamin E oil into the solution C, continuously stirring for 40-70min at 75 ℃, and uniformly mixing the medical-grade vitamin E oil and the solution C to prepare a solution D;
(5) and continuously and uniformly stirring the solution D until the temperature is reduced to the room temperature, thus completing the preparation.
And (3) testing:
the ointment prepared by the invention is subjected to cytotoxicity experiment, animal experiment and stability experiment verification.
Cytotoxicity was evaluated by using human epidermal fibroblasts and MTT method.
Animal experiments:
selecting 9 healthy and qualified ordinary-grade Wistar rats which are both male and female, randomly dividing the Wistar rats into 3 groups according to the weight, wherein each group comprises 3 Wistar rats, each group comprises one embodiment, each embodiment comprises 3 Wistar rats, and starting an experiment:
(1) carrying out conventional sterile treatment on all Wistar rats for experiments;
(2) marking round holes with the diameter of 2cm at 2cm beside two sides of a spinal column of Wistar rats, removing epidermis, dermis and subcutaneous connective tissue by using a scalpel, wherein 2 wounds are formed on each side, 4 wounds are formed on each Wistar rat, the four wounds are marked as A, B, Cl and C2 respectively, A is not processed and is marked as a blank control mark; b, applying a proper amount of similar marketed products containing bioactive glass skin wound dressings, uniformly smearing the dressings, and marking as a positive control mark; applying wound surface tissue self-derived regeneration repair ointments with the contents of the three examples to the Cl and C2 marks of Wistar rats in 3 groups respectively, and marking the wound surface tissue self-derived regeneration repair ointments as experimental marks; finally, wrapping with sterile gauze, adding the medicine once a day, and observing the healing condition of the wound surface.
The method for stability experiments comprises the steps of placing the prepared wound surface tissue self-derived regeneration and repair ointment for 0 month, 6 months, 12 months and 24 months, respectively using the wound surface tissue self-derived regeneration and repair ointment placed for the corresponding month for carrying out animal experiments of the first embodiment, the second embodiment and the third embodiment when the prepared wound surface tissue self-derived regeneration and repair ointment is placed for 0 month, 6 months, 12 months and 24 months, detecting performance indexes of the wound surface tissue self-derived regeneration and repair ointment, and carrying out animal experiments and cytotoxicity experiments.
The specific test results are as follows:
first, efficacy comparison of wound surface tissue self-induced regeneration repair ointment
Figure 316187DEST_PATH_IMAGE002
It can be seen from the above experimental comparison results that the wound tissue self-induced regeneration repair ointments prepared in the first, second and third embodiments have good biocompatibility and obvious healing promotion effect, and the third embodiment, namely, the best embodiment of adding 25 parts of regenerative medical materials, is compared with the blank control marker and the positive control marker, and the test group using the wound tissue self-induced regeneration repair ointment can obviously shorten the period of wound healing, and the healed wound has no scar and hyperplasia.
Secondly, comparing the stability experiment effect of the wound tissue self-induced regeneration repair ointment
Figure 46246DEST_PATH_IMAGE004
From the comparison effect of the experiments, it can be seen that the wound tissue self-induced regeneration repair ointment prepared in the second and third embodiments has good stability, and after being placed for 24 months, each performance index of the ointment has no significant change, and can still obviously promote the healing of the wound, which indicates that the dressing prepared by the method has good stability and can be stored for a long time.
In order to verify the superiority of the wound tissue self-regeneration repair ointment in the formula, the following experiments are carried out.
Third, the difference comparison of wound tissue self-induced regeneration and repair ointment in the formula
Figure 387229DEST_PATH_IMAGE006
Fourth, the comparison of the experimental effects of the third step
Figure DEST_PATH_IMAGE008
The experimental comparison results show that the wound tissue self-derived regeneration repair ointment prepared by the invention has superiority in the formula and has synergistic effect among the components, wherein a control group 1 and a control group 4 show that the regenerative medical material can be uniformly dispersed in the regenerative medical material under the condition that polyethylene glycol 4000 and polyethylene glycol 400 exist, and the polyethylene glycol is adsorbed on the surfaces of the regenerative medical material particles, so that the reaction can not occur on the surfaces of the regenerative medical material, and the stability of the product is maintained; the control group 2 shows that the glycerol and the regenerative medical material/polyethylene glycol 4000 have good compatibility, and comprehensively exert the advantage of inhibiting scars in the wound healing process after synergistic use; the control group 3 can find that the medical vitamin E oil has good moisture retention and repair components, and can enable the regenerative medical material to better play the roles of wound healing, repair and regeneration.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the scope of the present invention.

Claims (6)

1. The wound tissue self-induced regeneration repair ointment is characterized by comprising the following raw materials in parts by weight: 10-40 parts of regenerative medicine material, 05-20 parts of polyethylene glycol 40005, 30-80 parts of polyethylene glycol 4005-25 parts of glycerol and 0.5-3 parts of medical vitamin E oil;
each of the regenerative medical materialsThe components of the composition are as follows: p2 O510-25 parts of SiO220-60 parts of Na2O2-20 parts and CaO 15-45 parts.
2. The wound tissue self-induced regeneration repair ointment of claim 1, which is prepared from the following raw materials: 90% of the regenerative medical material has a particle size of less than 50 μm.
3. The wound tissue self-induced regeneration repair ointment of claim 1, which is prepared from the following raw materials: the particle size of 60-90% of the regenerative medical material is less than 30 μm.
4. The method for preparing the wound tissue self-derived regenerative repair ointment of claim 1, which comprises:
(1) putting polyethylene glycol 400 and polyethylene glycol 4000 into a container, heating to 75 ℃ to melt, and stirring for 10-20min at the same time until the polyethylene glycol 400 and the polyethylene glycol 4000 are uniformly mixed to prepare a solution A;
(2) adding glycerol into the solution A, stirring at 75 deg.C for 20-30min, and mixing glycerol and the solution A to obtain solution B;
(3) adding the regenerated medical material into the solution B for a certain number of times, stirring for 60-90min at 75 ℃, and uniformly mixing the regenerated medical material and the solution B to prepare a solution C;
(4) adding medical-grade vitamin E oil into the solution C, continuously stirring at 75 ℃ for 40-70min, and uniformly mixing the medical-grade vitamin E oil and the solution C to prepare a solution D;
(5) and continuously and uniformly stirring the solution D until the temperature is reduced to the room temperature, thus completing the preparation.
5. The method for preparing wound tissue self-induced regeneration and repair ointment according to claim 4, wherein the ointment comprises the following components: the regenerative medical material was added to solution B in equal amounts in four times.
6. The wound tissue self-derived regenerative repair ointment prepared by the preparation method of the wound tissue self-derived regenerative repair ointment as claimed in claim 4, wherein: the pH value of the wound tissue self-induced regeneration repair ointment is 7.3-7.8.
CN201810722993.1A2018-07-042018-07-04Wound tissue self-derived regeneration and repair ointment and preparation method thereofActiveCN110680832B (en)

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CN111529749B (en)*2020-04-152021-11-09杭州憶盛医疗科技有限公司Regenerative medical material for promoting tissue in-situ regeneration and preparation method thereof
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