CN111166941A - Tissue defect repairing agent and preparation method and using method thereof - Google Patents

Tissue defect repairing agent and preparation method and using method thereof Download PDF

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Publication number
CN111166941A
CN111166941A CN202010055422.4A CN202010055422A CN111166941A CN 111166941 A CN111166941 A CN 111166941A CN 202010055422 A CN202010055422 A CN 202010055422A CN 111166941 A CN111166941 A CN 111166941A
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China
Prior art keywords
tissue defect
particles
granules
repairing agent
sterile medium
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CN202010055422.4A
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Chinese (zh)
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王臻
卢霄
卢建熙
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Shanghai Bio Lu Biomaterials Co ltd
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Shanghai Bio Lu Biomaterials Co ltd
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Priority to CN202010055422.4A priority Critical patent/CN111166941A/en
Publication of CN111166941A publication Critical patent/CN111166941A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58Materials at least partially resorbable by the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00Materials characterised by their function or physical properties
    • A61L2400/06Flowable or injectable implant compositions

Abstract

The invention provides a tissue defect repairing agent and a preparation method and a using method thereof, wherein the preparation method of the tissue defect repairing agent comprises the following steps: step S1, respectively providing particles and granules which are biocompatible and can exert controllable biological effect and physical effect, and cleaning, drying and disinfecting the particles and the granules; step S2, performing surface treatment on the particles and the granules by adopting a biocompatible degradable sterile medium; step S3, the micro-particles and/or the granules and the sterile medium are configured into a tissue defect repairing agent according to a preset weight ratio, so that the tissue defect repairing agent has injectability. The technical scheme of the invention ensures that the tissue defect repairing agent has good biocompatibility, injectability and plasticity, can regulate and control tissue growth and reaction, material degradation performance and material bioactivity, and can be widely applied to the fields of biomedicine and veterinarian.

Description

Tissue defect repairing agent and preparation method and using method thereof
Technical Field
The invention relates to the field of biomedical materials, in particular to a tissue defect repairing agent and a preparation method and a use method thereof.
Background
Human tissue defects are caused by changes in tissue due to development and aging. The most common human tissue defect is facial wrinkles, and after the age of a human is increased to 25 years, the skin begins to age, the epidermis and the dermis become thin, the water content is reduced, the elasticity of collagen is lowered, and other factors cause fine skin wrinkles; the skin fine lines can be repaired by sun protection and nutrient supplement, or can be eliminated by adopting methods such as magnetic light waves, pulsed light and the like.
If the skin is further developed, the thinned skin excessively contracts through expression muscles, and dynamic wrinkles such as raised lines, frown lines, crow's feet and the like appear when the expression changes; at this time, local injection of botulinum toxin is commonly used to block the release of acetylcholine, paralyzing neuromuscular junctions to achieve wrinkle reduction. However, the axon can form a new motion end plate finally, meanwhile, the non-functional motion units are absorbed, and the muscle function is gradually recovered, so that the clinical curative effect can only be maintained for 3-6 months. Certainly, the biological wrinkle removing method of injecting platelet derived growth factors, epidermal growth factors, vascular growth factors, autologous skin fibroblasts and the like can achieve certain curative effect, but the method is expensive and has certain potential risks.
With the natural development rule of human aging, the skin can be aged and relaxed further, the collagen fibers and the elastic fibers of the dermis layer become less, and the wrinkles deepen to form irreversible static wrinkles; in this case, the common treatment methods are subcutaneous embedding and injection. The embedding method is that the very thin gold thread is embedded into the subcutaneous layer, and new tissue grows around the gold thread through foreign body reaction; the injection method is to inject a material (silica gel, hyaluronic acid, collagen, autologous fat particles, hydroxyapatite, polycaprolactone, polymethyl methacrylate, polylactic acid, etc.) into the depressions to support the collapsed skin from the inside. Wherein, the silica gel can not be absorbed by skin, and improper use can cause granuloma and persistent inflammation and deform tissues; hyaluronic acid is degraded by tissue metabolism, and the use time of hyaluronic acid is generally 6-12 months. In addition, the Ebefu is a novel injectable medical plastic and cosmetic material and consists of PMMA (polymethyl methacrylate) microspheres and collagen, the PMMA microspheres with smooth surfaces have the diameter of 32-40 micrometers, and a collagen solution with the mass ratio of 3.5% is used as a carrier, and a PMMA microsphere suspension solution is injected into a plastic part; after entering the plastic part, the PMMA microspheres are quickly wrapped by fibrous tissues so as not to move and degrade, the characteristics of the PMMA microspheres ensure that the PMMA microspheres are not digested and absorbed by macrophages and the irritation to the tissues is reduced to the minimum, and the PMMA microspheres can stimulate fibrocytes to synthesize and secrete collagen; after 1-3 months, the injected collagen is gradually degraded and replaced by the collagen of the human body, and the PMMA microspheres cannot be degraded and remain on the plastic part to play a permanent effect. In summary, neither the landfill method nor the injection filling method can control the distribution of the implant material in the skin, for example, the filling of the skin depression cannot be controlled, or the flatness of the skin surface cannot be regulated again, and the material cannot be extracted again after injection, and only waits for metabolic decomposition by the living body.
Therefore, as an ideal human tissue defect repair material, in addition to good biocompatibility and safety, the material must also have: (1) the injectability and plasticity of the material are favorable for minimally invasive treatment; (2) the growth and the reaction of the tissues can be regulated and controlled, so that the local tissues can be effectively proliferated; (3) the shape of the implanted material can be regulated, and the material can be shaped and fixed to realize the initial target required by clinical treatment; (4) the material degradation performance can be regulated and controlled, and the materials can be divided into non-degradation, slow degradation and fast degradation types according to the requirements of treatment parts and targets; (5) the biological activity of the material can be regulated and controlled, and the influence on the clinical curative effect caused by the premature absorption or excessive proliferation of the regeneration tissue is avoided. In order to provide the above-mentioned properties to the tissue repair material, a new method for preparing the tissue repair material needs to be provided.
Disclosure of Invention
The invention aims to provide a tissue defect repairing agent, a preparation method and a using method thereof, so that the tissue defect repairing agent has good biocompatibility, injectability and plasticity, can regulate and control tissue growth and reaction, material degradation performance and material bioactivity, and can be widely applied to the fields of biomedicine and veterinarian.
In order to achieve the above object, the present invention provides a method for preparing a tissue defect repair agent, comprising:
step S1, respectively providing particles and granules which are biocompatible and can exert controllable biological effect and physical effect, and cleaning, drying and disinfecting the particles and the granules;
step S2, performing surface treatment on the particles and the granules by adopting a biocompatible degradable sterile medium;
step S3, the micro-particles and/or the granules and the sterile medium are configured into a tissue defect repairing agent according to a preset weight ratio, so that the tissue defect repairing agent has injectability.
Optionally, the preparation method of the tissue defect repairing agent further comprises: step S4, filling the tissue defect repairing agent into a sterile container, and carrying out packaging and disinfection treatment.
Optionally, the material of the particles and the granules comprises inorganic material and/or organic material; the material of the particles and the microparticles comprises degradable material and/or non-degradable material; the shape of the microparticles and the particles comprises regular shapes and/or irregular shapes; the material of the sterile medium comprises at least one of collagen, sodium hyaluronate, chitosan and alginic acid.
Optionally, the degradable material comprises at least one of tricalcium phosphate, calcium sulfate, bioglass, polylactic acid, chitin, collagen, sodium hyaluronate, chitosan and alginic acid; the non-degradable material comprises at least one of hydroxyapatite, alumina, zirconia, polymethyl methacrylate, nylon, polyethylene and caprolactone; the regular shape comprises a sphere.
Optionally, the particle size of the particles is 0.01-50 μm; the particle size of the particles is 50-2000 mu m; the mass concentration of the sterile medium is 0.1-99.99%.
Optionally, in step S1, different cleaning media are selected to clean the particles and the granules according to different physical and chemical properties of the particles and the granules, the drying method is freeze drying, and the sterilization method is at least one of heating, high pressure and radiation irradiation; in the step S2, the surface treatment method is at least one of physical coating, chemical grafting and crosslinking; in the step S3, the injectability of the tissue defect repair agent is achieved by controlling at least one of the molecular weight, viscosity, and concentration of the sterile medium.
Optionally, in step S3, the tissue defect repair agent is prepared by mixing 1-99% by weight of the particles and 1-99% by weight of the sterile medium, and the tissue defect repair agent has a controllable physical effect; preparing the micro-particles with the weight ratio of 0.01-50% and the sterile medium with the weight ratio of 50-99.99% into the tissue defect repairing agent, wherein the tissue defect repairing agent has controllable biological effect; 1-99% of the particles, 0.1-10% of the particles and 1-99.89% of the sterile medium are mixed to prepare the tissue defect repairing agent, and the tissue defect repairing agent has adjustable physical effect and adjustable biological effect.
Optionally, the timeliness of the physical effect of the tissue defect repair agent is regulated according to the degradation performance, the size of the particle size, the concentration and the implantation mode of the particles; the timeliness of the biological effect of the tissue defect repair agent is regulated according to the degradation performance, the size of the particle size, the concentration and the implantation mode of the particles.
The invention also provides a tissue defect repairing agent, which is prepared by the preparation method of the tissue defect repairing agent.
The invention also provides a using method of the tissue defect repairing agent, and the tissue defect repairing agent is filled into a syringe or a special tool and injected into a tissue defect part.
Compared with the prior art, the technical scheme of the invention has the following beneficial effects:
1. the preparation method of the tissue defect repairing agent comprises the steps of respectively providing particles and granules which are biocompatible and can exert controllable biological effect and physical effect, and cleaning, drying and sterilizing the particles and the granules; then, carrying out surface treatment on the microparticles and the granules by adopting a sterile medium which has biocompatibility and is degradable; then, the micro-particles and/or the granules and the sterile medium are prepared into the tissue defect repairing agent according to a preset weight ratio, so that the prepared tissue defect repairing agent has good biocompatibility, injectability and plasticity, can regulate and control tissue growth and reaction, material degradation performance and material bioactivity, and can be widely applied to the fields of biomedicine and veterinarian.
2. The tissue defect repairing agent provided by the invention is prepared by the preparation method of the tissue defect repairing agent, so that the tissue defect repairing agent has good biocompatibility, injectability and plasticity, can regulate and control tissue growth and reaction, material degradation performance and material bioactivity, and can be widely applied to the fields of biomedicine and veterinarian.
3. According to the use method of the tissue defect repairing agent, the tissue defect repairing agent provided by the invention is filled into an injector or a special tool and is injected to a tissue defect part, so that the tissue defect repairing agent can well repair the defect part after being injected to the tissue defect part.
Drawings
Fig. 1 is a flowchart of a method for preparing a tissue defect repair agent according to an embodiment of the present invention.
Detailed Description
In order to make the objects, advantages and features of the present invention more clear, the tissue defect repairing agent proposed by the present invention, its preparation method and its use method are further described in detail with reference to fig. 1. It is to be noted that the drawings are in a very simplified form and are not to precise scale, which is merely for the purpose of facilitating and distinctly claiming the embodiments of the present invention.
An embodiment of the present invention provides a method for preparing a tissue defect repair agent, and referring to fig. 1, fig. 1 is a flowchart of a method for preparing a tissue defect repair agent according to an embodiment of the present invention, the method for preparing a tissue defect repair agent including:
step S1: respectively providing particles and granules which are biocompatible and can exert controllable biological effect and controllable physical effect, and cleaning, drying and sterilizing the particles and the granules;
step S2: subjecting said microparticles and said granules to a surface treatment using a biocompatible, degradable, sterile medium;
step S3: and (b) configuring the microparticles and/or the granules and the sterile medium according to a preset weight ratio so that the tissue defect repairing agent is injectable.
The preparation method of the tissue defect repairing agent provided by the embodiment is described in more detail as follows:
according to step S1, microparticles and particles that are both biocompatible and exert a controllable biological and physical effect are provided, respectively, and the microparticles and the particles are washed, dried and sterilized. The particles and the granules are biocompatible and the biological and physical effects caused by the particles and the granules are controllable, so that the particles and the granules can be well applied to the fields of biomedicine and veterinarian. The material of the particles and the granules comprises inorganic material or organic material, or comprises both inorganic material and organic material. And the material of the microparticle and the particle comprises degradable material or non-degradable material, or comprises degradable material and non-degradable material at the same time. The degradable material may include at least one of tricalcium phosphate, calcium sulfate, bioglass, polylactic acid, chitin, collagen, sodium hyaluronate, chitosan, and alginic acid; the non-degradable material may include at least one of hydroxyapatite, alumina, zirconia, polymethylmethacrylate, nylon, polyethylene, and caprolactone. It should be noted that the degradable material and the non-degradable material are not limited to the above-mentioned materials.
The shape of the microparticles and the particles may each comprise a regular shape or an irregular shape, or both a regular shape and an irregular shape. The regular shape includes a spherical shape, an elliptical shape, and the like. The fine particles may have a particle size of 0.01 to 50 μm (e.g., 0.1 μm, 1 μm, 10 μm, etc.); the particles may have a particle size of 50 μm to 2000 μm (e.g., 100 μm, 500 μm, 1000 μm, etc.). It should be noted that the particle size of the fine particles and the particles is not limited to the above range, and the particle size may be selected as appropriate according to the performance requirements of the tissue defect repair agent.
After the microparticles and the granules are provided, the microparticles and the granules may be subjected to a cleaning, drying, and sterilization process for subsequent use. Wherein, according to the difference of the physicochemical properties of the particles and the particles, different cleaning media (such as pure water, ethanol and the like) can be selected for cleaning the particles and the particles; the drying method can be freeze drying, and the freeze drying process conditions can be as follows: the freezing temperature is-90 ℃ to-20 ℃ (for example, -80 ℃, 50 ℃, 30 ℃ and the like), and the freezing time is 1h to 72h (for example, 10h, 30h, 60h and the like); the sterilization method may be at least one of heating, high pressure and radiation irradiation.
The microparticles and the granules are surface treated with a biocompatible degradable sterile medium according to step S2. The biocompatibility of the sterile medium enables its good application in the biomedical and veterinary fields; the particles and the granules are subjected to surface treatment through the sterile medium, so that when the particles and the granules are subsequently prepared into the tissue defect repairing agent with the sterile medium, the particles and the granules can be well combined with the sterile medium, the prepared tissue defect repairing agent has good stability, and the tissue defect repairing agent can be better applied to the fields of biomedicine and veterinarian.
The material of the sterile medium can comprise at least one of collagen, sodium hyaluronate, chitosan and alginic acid; it should be noted that the material of the sterile medium is not limited to the above-mentioned kind, and may include any biocompatible degradable material. The mass concentration of the sterile medium can be 0.1-99.99% (e.g., 1%, 10%, 50%, etc.); it should be noted that the mass concentration of the sterile medium is not limited to the above range, and an appropriate concentration may be selected according to the performance requirements of the tissue defect repairing agent.
The method of surface treating the microparticles and the particles with the sterile medium may be at least one of physical coating, chemical grafting, and crosslinking. The physical coating is to coat the sterile medium on the surfaces of the particles and granules by a physical method, so that the particles and the granules can be wrapped; chemical grafting is to utilize the reactive groups on the particles and the particles to chemically react with molecular chains in the sterile medium; the crosslinking is that molecular chains in the sterile medium are respectively connected with molecular chains in the particles and the particles by covalent bonds to form a net-shaped or body-shaped high molecular polymer.
According to step S3, the microparticles and/or the granules and the sterile medium are configured with a tissue defect repair agent according to a preset weight ratio, so that the tissue defect repair agent is injectable. The sterile medium is injectable, and the injectability of the tissue defect repair agent can be achieved by controlling at least one of the molecular weight, viscosity, and concentration of the sterile medium. The tissue defect repairing agent has injectability, so that the tissue defect repairing agent can be injected to a treatment part to immediately play roles of filling, extruding, pushing and the like, and further achieve a treatment target.
The step of deploying the tissue defect repair agent may comprise: configuring 1-99% (e.g., 10%, 50%, 90%, etc.) by weight of the particles to 1-99% (e.g., 10%, 50%, 90%, etc.) by weight of the sterile medium into the tissue defect repair agent, the tissue defect repair agent having a controllable physical effect, e.g., configuring 30% by weight of tricalcium phosphate particles to 70% by weight of collagen liquid into the tissue defect repair agent; alternatively, 0.01% to 50% (e.g., 0.1%, 1%, 10%, etc.) by weight of the microparticles and 50% to 99.99% (e.g., 60%, 90%, etc.) by weight of the sterile medium are formulated into the tissue defect repair agent, which has a controllable biological effect, e.g., 20% by weight of the hydroxyapatite microparticles and 80% by weight of the sodium hyaluronate solution are formulated into the tissue defect repair agent; alternatively, 1% to 99% (e.g., 10%, 50%, 90%, etc.) by weight of the particles, 0.1% to 10% (e.g., 1%, 5%, etc.) by weight of the microparticles, and 1% to 99.89% (e.g., 10%, 50%, 80%, etc.) by weight of the sterile medium are formulated into the tissue defect repair agent, which has a controllable physical effect and a controllable biological effect, i.e., has a dual effect, e.g., 20% by weight of tricalcium phosphate particles, 5% by weight of hydroxyapatite microparticles, and 75% by weight of collagen protein fluid are formulated into the tissue defect repair agent. Wherein the required tissue defect repair agent can be obtained by adjusting the weight ratio of at least one of the particles, the microparticles and the sterile medium; the tissue defect repairing agent with a proper proportion can be selected and prepared according to the treatment requirement. The weight ratio is the weight of each of the particles, microparticles, sterile medium to the total mixture (i.e., the tissue defect repair agent as disposed).
After the tissue defect repairing agent is injected into the treatment site, because the sterile medium has degradability, the microparticles and the particles still maintain the physical effect of increasing capacity at the treatment site after the sterile medium is degraded and absorbed, and continue to exert the treatment effect; and the particles can stimulate the proliferation of fiber cells and the secretion of collagen at the treatment part to form the biological effect of fiber tissue proliferation, thereby playing a role in treatment. And, when the tissue defect repair agent has both the particles and the microparticles, then the physical effect and the biological effect act together therapeutically.
In addition, the time effectiveness of the physical effect of the tissue defect repair agent can be regulated according to the degradation performance of the particles (namely the material of the particles comprises degradable materials and/or non-degradable materials), the particle size, the concentration and the implantation mode; the time effectiveness of the biological effect of the tissue defect repair agent can also be regulated according to the degradation performance of the particles (namely, the material of the particles comprises degradable materials and/or non-degradable materials), the granularity, the concentration and the implantation mode. Wherein the microparticles of degradable material are capable of exerting a time-limited tissue-stimulating effect, the material losing its filling and tissue-stimulating effects after degradation; the particles of non-degradable material can exert long-acting filling and tissue stimulation effects, and can also not exert the tissue stimulation effect after being wrapped and fixed by the tissue, but still keep the filling effect.
In addition, the preparation method of the tissue defect repairing agent further comprises the following steps: step S4, filling the tissue defect repairing agent into a sterile container, and carrying out packaging and disinfection treatment. The tissue defect repairing agent can also be directly filled into a syringe and subjected to packaging and sterilization treatment.
As can be seen from steps S1 to S4, the tissue defect repair agent is simple in preparation method, and the prepared tissue defect repair agent has excellent biocompatibility and safety, and also has the following excellent properties: (1) the injectability and plasticity of the material are favorable for minimally invasive treatment; (2) the growth and the reaction of the tissues can be regulated and controlled, so that the local tissues can be effectively proliferated; (3) the shape of the implanted material can be regulated, and the material can be shaped and fixed to realize the initial target required by clinical treatment; (4) the material degradation performance can be regulated and controlled, and the materials can be divided into non-degradation, slow degradation and fast degradation types according to the requirements of treatment parts and targets; (5) the biological activity of the material can be regulated and controlled, and the influence on the clinical curative effect caused by the premature absorption or excessive proliferation of the regeneration tissue is avoided. Therefore, the simplicity of the preparation method of the tissue defect repair agent and the excellence in performance enable the tissue defect repair agent to be widely used in the biomedical and veterinary fields.
In summary, the preparation method of the tissue defect repairing agent of the present invention comprises: step S1, respectively providing particles and granules which are biocompatible and can exert controllable biological effect and physical effect, and cleaning, drying and disinfecting the particles and the granules; step S2, performing surface treatment on the particles and the granules by adopting a biocompatible degradable sterile medium; step S3, the micro-particles and/or the granules and the sterile medium are configured into a tissue defect repairing agent according to a preset weight ratio, so that the tissue defect repairing agent has injectability. The preparation method of the tissue defect repairing agent provided by the invention enables the prepared tissue defect repairing agent to have good biocompatibility, injectability and plasticity, can regulate and control tissue growth and reaction, material degradation performance and material bioactivity, and can be widely applied to the fields of biomedicine and veterinarian.
The tissue defect repairing agent is prepared by the preparation method of the tissue defect repairing agent. The tissue defect repairing agent prepared by the preparation method of the tissue defect repairing agent provided by the invention has good biocompatibility and safety, and also has the following excellent performances: (1) the injectability and plasticity of the material are favorable for minimally invasive treatment; (2) the growth and the reaction of the tissues can be regulated and controlled, so that the local tissues can be effectively proliferated; (3) the shape of the implanted material can be regulated, and the material can be shaped and fixed to realize the initial target required by clinical treatment; (4) the material degradation performance can be regulated and controlled, and the materials can be divided into non-degradation, slow degradation and fast degradation types according to the requirements of treatment parts and targets; (5) the biological activity of the material can be regulated and controlled, and the influence on the clinical curative effect caused by the premature absorption or excessive proliferation of the regeneration tissue is avoided. Therefore, the excellence in the performance of the tissue defect repair agent enables the tissue defect repair agent to be widely used in the biomedical and veterinary fields.
One embodiment of the invention provides a use method of a tissue defect repairing agent, wherein the tissue defect repairing agent provided by the invention is filled into a syringe or a special tool and is injected into a tissue defect part. The tissue defect repairing agent is prepared by the preparation method of the tissue defect repairing agent provided by the invention, so that the tissue defect repairing agent has excellent performance, and the tissue defect repairing agent can well repair the defective part after being injected into the tissue defect part.
The above description is only for the purpose of describing the preferred embodiments of the present invention, and is not intended to limit the scope of the present invention, and any variations and modifications made by those skilled in the art based on the above disclosure are within the scope of the appended claims.

Claims (10)

1. A method of preparing a tissue defect repair agent, comprising:
step S1, respectively providing particles and granules which are biocompatible and can exert controllable biological effect and physical effect, and cleaning, drying and disinfecting the particles and the granules;
step S2, performing surface treatment on the particles and the granules by adopting a biocompatible degradable sterile medium;
step S3, the micro-particles and/or the granules and the sterile medium are configured into a tissue defect repairing agent according to a preset weight ratio, so that the tissue defect repairing agent has injectability.
2. The method of preparing a tissue defect repair agent according to claim 1, further comprising: step S4, filling the tissue defect repairing agent into a sterile container, and carrying out packaging and disinfection treatment.
3. The method of preparing a tissue defect repair agent according to claim 1, wherein the material of the microparticles and the particles comprises an inorganic material and/or an organic material; the material of the particles and the microparticles comprises degradable material and/or non-degradable material; the shape of the microparticles and the particles comprises regular shapes and/or irregular shapes; the material of the sterile medium comprises at least one of collagen, sodium hyaluronate, chitosan and alginic acid.
4. The method of claim 3, wherein the degradable material comprises at least one of tricalcium phosphate, calcium sulfate, bioglass, polylactic acid, chitin, collagen, sodium hyaluronate, chitosan, and alginic acid; the non-degradable material comprises at least one of hydroxyapatite, alumina, zirconia, polymethyl methacrylate, nylon, polyethylene and caprolactone; the regular shape comprises a sphere.
5. The method for producing a tissue defect repair agent according to claim 1, wherein the particle size of the fine particles is 0.01 μm to 50 μm; the particle size of the particles is 50-2000 mu m; the mass concentration of the sterile medium is 0.1-99.99%.
6. The method for preparing a tissue defect repair agent according to claim 1, wherein in step S1, different cleaning media are selected for cleaning the particles and the granules according to the difference of physicochemical properties of the particles and the granules, the drying method is freeze-drying, and the sterilization method is at least one of heating, high pressure and radiation irradiation; in the step S2, the surface treatment method is at least one of physical coating, chemical grafting and crosslinking; in the step S3, the injectability of the tissue defect repair agent is achieved by controlling at least one of the molecular weight, viscosity, and concentration of the sterile medium.
7. The method of claim 1, wherein in step S3, the tissue defect repair agent is prepared by mixing 1-99% by weight of the particles and 1-99% by weight of the sterile medium, and has a controllable physical effect; preparing the micro-particles with the weight ratio of 0.01-50% and the sterile medium with the weight ratio of 50-99.99% into the tissue defect repairing agent, wherein the tissue defect repairing agent has controllable biological effect; 1-99% of the particles, 0.1-10% of the particles and 1-99.89% of the sterile medium are prepared into the tissue defect repairing agent, and the tissue defect repairing agent has a controllable physical effect and a controllable biological effect.
8. The method of claim 7, wherein the time effectiveness of the physical effect of the tissue defect repair agent is controlled according to the degradation performance, the size of the particles, the concentration of the particles, and the implantation mode; the timeliness of the biological effect of the tissue defect repair agent is regulated according to the degradation performance, the size of the particle size, the concentration and the implantation mode of the particles.
9. A tissue defect repair agent produced by the production method for a tissue defect repair agent according to any one of claims 1 to 8.
10. A method of using the tissue defect repair agent of claim 9, wherein the tissue defect repair agent is loaded into a syringe or a special tool and injected into the tissue defect site.
CN202010055422.4A 2020-01-17 2020-01-17 Tissue defect repairing agent and preparation method and using method thereof Pending CN111166941A (en)

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