CN111973797B

CN111973797B - Non-invasive implantation high-viscosity adhesive material for orthopedics department and preparation method and application thereof

Info

Publication number: CN111973797B
Application number: CN202010919018.7A
Authority: CN
Inventors: 曹建中; 曹宏
Original assignee: Hunan Aoxing Biomedical Co ltd
Current assignee: Cao Jianzhong
Priority date: 2020-09-04
Filing date: 2020-09-04
Publication date: 2022-06-03
Anticipated expiration: 2040-09-04
Also published as: WO2022048126A1; CN111973797A

Abstract

The invention discloses a non-invasive implantation high-viscosity adhesive material for orthopedics department, which has high viscosity, good plastic film property, stable storage property and convenient operation site preparation and implantation, and a preparation method and application thereof, wherein the adhesive material is prepared from the raw materials of PLGA, beta-TCP, sodium chloride, ethyl acetate, distilled water, medical adhesive, hydroxypropyl polyfumarate and N-vinyl propyl pyrrolidone in proportion; or PLGA, beta-TCP, phosphate buffer solution, etc.; respectively preparing high-viscosity glue water dispersible granules and a glue solution; adding an organic acid solvent and an adhesive solution into the high-viscosity glue dispersing granule to obtain a noninvasive implanting high-viscosity glue solution for orthopedics; the invention utilizes the field random matching and use of prefabricated materials, accurately controls the curing time and ensures the time interval of the surgical implantation; the bone cement is quickly cured at body temperature, has good biocompatibility and controllable biodegradation, accelerates bone healing, forms a plastic film material, has high viscosity, and improves the reconstruction and repair strength; the minimally invasive implantation is accurate and convenient.

Description

Non-invasive implantation high-viscosity adhesive material for orthopedics department and preparation method and application thereof

Technical Field

The invention relates to the technical field of biological preparations, in particular to a non-invasive implantation high-viscosity adhesive material for orthopedics, a preparation method and application thereof.

Background

The history of applying medical adhesives by human beings is long, the complexity of operations is reduced in recent decades, and the medical adhesives are rapidly developed and widely applied. In surgery, medical adhesives are used for the local adhesion and repair of certain organs and tissues; stopping the capillary blood leakage at the suture position after the operation; the gynecological department is used for sticking and blocking the oviduct to finish ligation; dental use for dental restorations; the combination and positioning of bones and joints in orthopedic surgery.

The adhesive for bones has good biocompatibility, degradability, no organ toxicity, no cytotoxicity and no carcinogenic teratogenesis, can realize rapid adhesion at normal temperature, does not influence callus growth, can be degraded within a certain time, and has good adhesion strength and durability to ensure fracture healing. Various adhesives for orthopedics at present mainly comprise alpha-cyanoacrylate; bone cement-based adhesives (bone cement, calcium phosphate-based bone cement, magnesium phosphate-based bone cement); composite adhesive (composite coagulant, composite water (blood) solvent, composite reinforcing agent, composite plasticizer and composite bioactive factor); fibrin class; sodium alginate mixed gel. Biomaterials are classified by their application properties into anticoagulant materials (cardiovascular materials), dental materials, orthopedic materials, ophthalmic materials, adsorption detoxification materials (for blood perfusion), prosthetic materials, sustained release materials, bioadhesive materials, membrane materials for dialysis and ultrafiltration, disposable medical materials, and the like. Classifying according to the use requirements of medical materials: non-implantable materials, blood-contacting materials, degradable and absorbable materials.

The newly developed materials are polyglycolic acid (Polyglycolide) and polylactic acid (polylactade) based polymers, which are made into screws and internal fixation rods for internal fixation of clinical fractures. Can be degraded and absorbed in vivo after fracture healing, and is not needed to be taken out after operation. After the polymer material is implanted into a body for 48 hours, the screw and the rod absorb water and expand, can strengthen themselves and have better internal fixation property. And does not interfere fracture healing and has no phenomenon of bone dissolution. Has become a commercial market at present, and a plurality of countries are abroad used for internally fixing the fracture in and around the joint and the fracture of the hand. Of these, finland has accumulated over 2 million cases in 1990, and china has started to use it since 1993.

However, the mechanical strength and degradation rate vary from polymer to polymer. In addition, repeated in vivo biological animal experiments show that the polymer implanted into the body is easy to cause edema around the implantation, inflammatory cell infiltration and multinucleated giant cells occur, and fibroblasts proliferate to form fibers; meanwhile, the particles formed by degrading the polymer are swallowed by macrophages, and have delayed inflammatory reaction when being implanted into bones, and the incidence is still high.

Although, the biodegradable material is finally decomposed into H in the human body₂O₂And CO₂The toxicity is extremely low, but the irritation to tissues is large, so that effusion and swelling of the tissues can be caused; the particles degraded by the material can be considered as foreign body stimulation by human body to induce rejection reaction-macrophage reaction. Therefore, the tissue compatibility is still not as good as the internal fixation performance of the currently applied metal.

The clinical common fracture and bone defect of various diseases such as trauma, infection, tumor, osteonecrosis, congenital deformity and the like makes more and more important the minimally invasive injectable biomaterial for fracture and bone defect repair, and various injectable materials such as bone cement, natural derivatives, synthetic polymers and the like are developed.

The existing fracture in-situ mineral phase forming material is prepared by injecting a viscous wetting agent prepared from inorganic calcium and inorganic phosphorus into a fracture gap, wherein the viscous wetting agent becomes hard within a few minutes to form phosphorus calcium carbonate, and the phosphorus calcium carbonate is completely cured within 12 hours to enable fracture to be firmly connected. Before the fracture is completely cured, the bonded rigidity and hardness of the fracture are insufficient, and plaster is still required to be externally fixed to prevent the fracture from being dislocated.

The bone cement is a bone repair material which is convenient to operate in clinical surgical operations, can be randomly shaped and automatically solidified as cement, and has wide application in the fields of bone repair and the like. One material currently available as bone cement is polymethyl methacrylate (PMMA), which has a significant problem with biocompatibility due to its composition completely different from natural bone tissue. Although the traditional inorganic calcium phosphate bone cement has good biocompatibility and high bioactivity, the mechanical strength is too low, the compressive strength is small, the tensile strength is low, the brittleness is high, and the elastic modulus is greatly higher than that of natural bone. In addition, it has poor injectability, cannot fill and repair precisely the place to be treated according to the defect site, and has problems in that it is difficult to solidify body fluid and blood, etc.

Molecular design of polymers is an important issue for biomacromolecule scientists at present, and the problems of inference, prediction, constituent atoms of macromolecular biomaterials, molecular species, binding and aggregation states and the like are analyzed, and the specific conformation of the structure, the organization and the form of the molecules is described. Molecular design of medical biopolymer polymers has been carried out with the goal of how to synthesize and manufacture a high molecular biomaterial with specified properties and structure. The further practical connection of molecular design is "material design", which belongs to the field of objective science and is the subject of engineering.

The biodegradable polymer has the advantages of excellent mechanical property, good biocompatibility and the like, and is more and more convenient to be applied in the biomedical field such as bone transplantation, bone cement, drug controlled release, tissue engineering scaffolds and the like. At present, autograft and synthetic material implantation methods are mostly adopted for treating bone defects, but the autograft bone quantity is limited by sources, so that the pain of secondary operation is caused, accurate modeling is difficult according to defect parts, and allograft transplantation can become a disease infection source. Synthetic materials such as PMMA bone cement are permanently implanted, but may cause many side effects such as infection, bone corrosion, etc., and for artificial bone materials implanted into the human body, it is required that she can withstand corrosion and dissolution of body fluids, have good biocompatibility and bioactivity, and also have good chemical stability and mechanical properties.

beta-TCP (beta-tricalcium phosphate), a powder, has been used clinically since the 70 s as an artificial bone substitute material. The components of the beta-TCP are similar to the composition of bone minerals, the ratio of Ca ions to P ions in the beta-TCP is 1.5:1, the beta-TCP is degraded into Ca ions and P ions in vivo and then provided for new bone tissues to be gradually replaced by the new bone tissues, and the beta-TCP has good biocompatibility. As an implant material, the beta-TCP has good biodegradability. In general, there are two pathways for biodegradation processes, i.e., humoral and cell-mediated processes. And the beta-TCP has a communicated macroporous structure which is beneficial to the immersion of body fluid and a microporous structure which is beneficial to the growth of tissue cells. After being implanted into a body for a period of time, the beta-TCP is subjected to ceramic biodegradation, no foreign matter is finally left, the material is completely absorbed to form a new strand of plastic, the plastic is not affected by the material, and the strength of the new bone is changed by different preparation processes due to the bonding strength of the new bone and the material, so that the pore mechanism and the physical and chemical properties (biological absorptivity, mechanical strength, pore structure and the like) of the material can meet different clinical application requirements. However, the beta-TCP has low fatigue strength, large brittleness and fracture resistance and impact resistance which can not meet the requirements of high-load artificial bones.

The degradable biomaterials applied to the rice-in-tube at present comprise polyglycolic acid (PGA) and polylactic acid (PLA), but the degradable biomaterials have the defects of no hydrophilicity and the like due to the lack of reactive functional groups in chemical structures, so that the application of the degradable biomaterials as bone repair materials is greatly limited. Therefore, the synthesis of a new biodegradable material is a subject of development in the medical field.

Generally, such bone adhesives are used as one-component, industrial, solvent-free adhesives, which are rapidly cured at ordinary temperatures in use and cured within 10 to 30 seconds by tissue fluid and blood polymerization after being implanted in the body. The curing time is not easy to control. According to different bone injury conditions, the dosage of the bone cement used in the operation process is different, and sometimes the dosage is small, so that the rest bone cement is not beneficial to storage, and even the bone cement is rapidly solidified due to untimely use or storage, thereby causing waste. Therefore, there is a need for a bone cement that is stable in storage and easy to apply during use.

PLGA, a polylactic acid-glycolic acid copolymer, is a degradable functional polymer organic compound formed by random polymerization of two monomers, lactic acid and glycolic acid, has good biocompatibility, no toxicity, and good properties of encapsulation and film formation, and is widely applied to the fields of pharmacy, medical engineering materials and modern industry. PLGA is certified by FDA in the united states and is officially incorporated into the united states pharmacopeia as a pharmaceutical excipient. The degradation products of PLGA are lactic acid and glycolic acid, which are also byproducts of human metabolic pathways, and thus it has no toxic side effects when applied in medicine and biomaterials. Of course, lactose deficient ones are excluded. The method is widely applied to the biomedical field, such as skin transplantation, wound suture, in-vivo implantation, micro-nano particles and the like, by adjusting the monomer ratio and further changing the degradation time of PLGA.

Poly (hydroxypropyl) fumarate (PPF) is an unsaturated linear polyester, belongs to water degradable substances, is an ideal biodegradable material, can be degraded in a living body to generate fumaric acid and Propylene Glycol (PG) degradation products, can be discharged out of the body through normal metabolism, and has no influence on in-vivo systems such as pH value and the like. PPF with proper polymerization degree can be solidified at body temperature, and a material with good mechanical property can be obtained by controlling the molecular weight of the PPF. And the fumaric acid unsaturated double bond of the PPF can react with other cross-linking agent molecules to generate a cross-linked reticular polymer material which is used as a scaffold material to induce the regeneration of bones. Degradable propylene glycol fumarate. The PPG is biodegradable and can be molded at random at body temperature, and the PPF has good fluidity before curing, so that the PPG can be used as an injectable filling material and can be well used for repairing and reconstructing the kneeling-free bone defect part.

N-vinyl pyrrolidone, i.e., N-vinyl pyrrolidone. N-ethyl-2-pyridone, a Chinese synonym; 1-vinyl-2-pyrrolidone; 1-vinyl-2-pyridone; 1-vinyl-2-pyrrolidone; 99% STAB. WITH0.1% SODIUMHYDROXID; chemical book 1-vinyl-2-pyrrolidone (containing stabilizer N, N' -di-sec-butyl-p-phenylenediamine); 1-vinyl-2-pyrrolidone, 99% STAB. WITH0.1% SODIUMHYDROXIDE; vinyl-2-pyrrolidone. English name: N-Vinyl-2-pyrollidone. Chemical formula C6H9NO, molecular weight 111.142. The density is 20 ℃, and the concentration is 1.030-1.060 g/mL; 25 ℃ and 1.04 g/mL. Molar volume: 97.1 cm³And/mol. A colorless liquid. Easy to polymerize into polyvinylpyrrolidone. Can be mixed with water, ethanol, ether and other organic solvents, and can be easily copolymerized with other vinyl compounds. The ultraviolet curing coating is mainly used for polymers or copolymers, and can also be used for reactive diluents of polymer systems, and ultraviolet curing coatings for wall, floor and other decorations.

The ultrafine particles are fine powder materials having a diameter of 1 μm or less. Particles having a size of 0.5nm to 100nm and located in a region where an atomic cluster and a macroscopic object intersect are generally called ultrafine particles. The ultrafine particle material has the characteristics of electricity, heat, optics and the like, and has good application in the fields of electronics, chemical engineering, nuclear technology rights and the like.

Phosphate Buffered Saline (PBS) is one of the most widely used buffer solutions commonly used in biological research. PBS can be the english abbreviation for three solutions, phosphate buffered saline, phosphate buffered sodium, respectively. Because of their secondary dissociation, buffered pH ranges are wide. The concentration of the buffer solution is easy to configure, the influence of pH value on temperature is small, the buffer capacity is strong, and the change of the pH value after dilution is small. The phosphate buffer adjusts the pH without affecting the chemical reaction to allow the chemical reaction to proceed under optimal conditions. However, phosphate buffers are easily associated with the common calcium ion Ca²⁺、Mg²⁺And some heavy metal ions associate to form a precipitate; can inhibit certain biochemical reaction processes, such as inhibiting catalytic processes of certain enzymes, and the like. The buffer helps to maintain a constant pH, and the solution typically has an osmotic pressure and an ionic concentration that is similar to the pH of the human body (isotonic). For example, PBS is phosphate buffered saline at pH7.4, is fixed at pH and is isotonic with human blood, and is therefore commonly used in molecular cloning and cell culture experiments. The more common pH values used for protein experiments were pH6.8 and pH 8.8. The preparation method is different, the pH value is different, and the biological effects are not completely the same. Biologically commonly used PBS is a neutral phosphate buffer solution unless otherwise specified. The buffer helps to maintain a constant pH. The osmotic pressure and ionic concentration of the solution are generally similar to the pH of the human body (isotonic).

Disclosure of Invention

The invention aims to provide a non-invasive implantation high-viscosity adhesive material for orthopedics, which has high viscosity, good plastic film property, stable storage property and convenient preparation and implantation in an operation site, and a preparation method and application thereof.

The invention adopts the following technical scheme to realize the aim of the invention, and discloses an orthopedic noninvasive implantation high-viscosity adhesive material which is characterized by being prepared from the following raw materials in parts by weight:

PLGA: beta-TCP: sodium chloride: ethyl acetate: distilled water: medical adhesive: polyhydroxypropylfumarate (PPF): n-vinyl pyrrolidone =760mg to 1520 mg: 240 mg-480 mg: 20 mg-40 mg: 8 mL-12 mL: 100 mL-200 mL: 19 mL-38 mL: 3 mL-6 mL: 3 mL-6 mL;

or PLGA: beta-TCP: phosphate buffer solution: sodium chloride: distilled water: medical adhesive: polyhydroxy-propyl polyfumarate: n-vinylpyrrolidone =760mg to 1520 mg: 240 mg-480 mg: 30 mL-50 mL: 10 mg-20 mg: 100 mL-200 mL: 19 mL-38 mL: 3 mL-6 mL: 3mL to 6 mL.

The PLGA ratio (molar ratio) is DL-LA/GA = 75/25; the beta-TCP is nano-powder; the pH value of the phosphate buffer solution is 7.2.

A preparation method of a noninvasive implantation high-viscosity glue material for orthopedics department comprises the following steps:

dissolving PLGA, beta-TCP and sodium chloride in ethyl acetate according to a ratio to obtain a solution A;

or dissolving PLGA and beta-TCP in phosphate buffer solution to obtain solution B; standby;

dissolving PLGA, beta-TCP and sodium chloride in distilled water to obtain a solution C; standby;

thirdly, injecting the solution A or the solution B into the solution C under the stirring of the rotating speed of 1000 revolutions per minute at the temperature of-4-8 ℃, and continuously stirring under the magnetic force condition until the PLGA, the beta-TCP and the sodium chloride become ultrafine particles and are solidified;

fourthly, performing centrifugal separation on the product obtained in the step three at a speed of 1000 rpm, washing with water, drying to obtain high-viscosity glue ultrafine particle powder, adding required amount of distilled water, dispersing uniformly, and packaging to obtain high-viscosity glue water dispersible granules;

fifthly, dissolving the medical adhesive, the poly-hydroxypropyl fumarate (PPF) and the N-vinylpyrrolidone in distilled water according to the ratio, stirring at 6-10 ℃, polymerizing the medical adhesive, the poly-hydroxypropyl fumarate (PPF) and the N-vinylpyrrolidone to obtain a sticky solution, and then performing centrifugal separation at 300 revolutions per minute to obtain an adhesive solution for later use;

sixthly, after the high-viscosity adhesive water dispersible granules obtained in the fourth step and the adhesive solution obtained in the fifth step are subjected to cobalt 60 irradiation sterilization for 6-7 days, the adhesive water dispersible granules and the adhesive solution are combined and packaged according to the proportion to be stored in required specifications, and the spare combined noninvasive implanting high-viscosity adhesive material for orthopedics is obtained.

The solution A in the step of the invention comprises the following raw materials: beta-TCP: sodium chloride: ethyl acetate =380mg to 760 mg: 120 mg-240 mg: 10 mg-20 mg: 8 mL-12 mL;

the solution B is prepared from PLGA: beta-TCP: phosphate buffer =380mg to 760 mg: 120 mg-240 mg: 30 mL-50 mL;

the preparation method comprises the following steps that the raw material ratio of the solution C is PLGA: beta-TCP: sodium chloride: distilled water =380mg to 760 mg: 120 mg-240 mg: 10 mg-20 mg: 50 mL-100 mL;

the diameter of the ultrafine particles in the step three is 0.1-0.2 microns;

the drying in the step four is drying for 2 to 1 hour at 60 to 120 ℃ or freeze drying;

the adhesive solution in the step fifthly is prepared from the following raw materials in parts by weight: polyhydroxypropylfumarate (PPF): n-vinylpyrrolidone: distilled water =19mL to 38 mL: 3 mL-6 mL: 3 mL-6 mL: 50mL to 100 mL.

The step sixteenth is that the bone department implants the high-viscosity adhesive material in a noninvasive mode, and the high-viscosity adhesive water dispersible granules are packaged and proportioned according to the following steps: adhesive solution = 5-10 g/bottle (penicillin bottle): 25-50 mL/bottle.

An application of a noninvasive implantation high-viscosity adhesive material for orthopedics in the operation of treating fracture, osteopathy and bone tumor (minimally invasive injection implantation of fracture, osteopathy part or operation open bone filling) is characterized in that an organic acid solvent and an adhesive solution which have no toxic or side effect on a human body are sequentially added into high-viscosity adhesive water dispersible granules according to a proportion for dissolution, hydroxypropyl polyfumarate (PPF) and N-vinyl pyrrolidone can be biodegraded and are crosslinked with a medical adhesive, and the high-viscosity adhesive water dispersible granules and acetic acid are added to be compounded into a viscous suspension solution, so that the noninvasive implantation high-viscosity adhesive solution for orthopedics is obtained.

The organic acid solvent is acetic acid.

The dissolution proportion of the invention is high viscosity glue water dispersible granule: adhesive solution: acetic acid =5 g: 25mL of: 0.5 mL.

The medical adhesive is a commercially available adhesive and is produced by Beijing Kangpi special medical instrument limited company. The product is colorless transparent liquid, the main component is alpha-cyano n-butyl acrylate, and the product is provided with trace additives; according to clinical requirements, the device is provided with a suction tube, a glue spraying bottle and a rotary arm spraying pump. Can be used as glue for operation without suture, can be used for hemostasis of human body, beautifying glue and animal experiment, and has no toxic and side effects.

The N-vinyl pyrrolidone is produced by Jiangsu Nantong Runfeng petrochemical company Limited.

The PLGA is produced by Shenzhen Lushengbao Biotech Limited, and the proportion of DL-LA/GA: 75/25, respectively;

DL-LA, racemic Lactide wood DL-LA, namely racemic Lactide (3,6-Dimethyl-1,4-dioxane-2,5-dione) English name DL-Lactide (3,6-Dimethyl-1,4-dioxane-2,5-dione) CAS. R.NO:95-96-5 molecular formula C6H8O4 molecular weight 144.13 melting point 127 ℃, water content less than or equal to 0.4%, heavy metal less than or equal to 5ppm, free acid (CH3ONa g/kg) less than or equal to 1, ash less than or equal to 0.05% and purity more than or equal to 99.5%;

GA, i.e. Glycolic acid, alias Glycolic acid, english name Glycolic acid, chemical formula C2H4O3, molecular weight 76.05, melting point 78-79 ℃, relative density (water = 1): 1.49, has no boiling point, is heated to decompose into formaldehyde, carbon monoxide and water at 100 ℃, the formaldehyde can further form paraformaldehyde or formic acid, is soluble in water, methanol, ethanol and ethyl acetate, is slightly soluble in diethyl ether and is insoluble in hydrocarbons.

The ethyl acetate of the present invention is commercially available as analytical grade.

The phosphate buffer solution is a commercially available 99.9% phosphate buffer solution, and the pH value is 7.2. It is a water-based salt solution containing sodium chloride, phosphate, and (in some formulations) potassium chloride and potassium phosphate. The sodium chloride gradually dissolves in the bone to form a pore canal, and the fracture healing is promoted. Therefore, the invention adopts the phosphate buffer solution with specific pH value of 7.2 to dissolve PLGA and beta-TCP in the phosphate buffer solution, the phosphate buffer solution with pH value of 7.2 generates a good foaming agent in the material to prepare a porous solidified material, thereby increasing the porosity of the product in bone filling, and enabling the implanted material to have enough pore channels to enable tissues to grow in, thereby promoting bone healing and further effectively shortening the healing time.

When the invention is used, an orthopaedics professional resets the fracture under the operation of a C-shaped arm X-ray machine, and the alignment of the side position sheet is well aligned through the C-shaped arm film and television and the X-ray machine; after acetic acid and an adhesive solution are sequentially added into the prepared high-viscosity glue water dispersible granules which are implanted into the high-viscosity glue material in a non-invasive manner for orthopedics on an operating table for dissolution, the prepared high-viscosity glue water dispersible granules are implanted into the parts of the fracture and the bone disease in a minimally invasive injection manner, and the fracture is effectively fixed by bonding and fixing the parts of the fracture and the bone disease; when the operation is opened, various bone defects with different shapes and sizes can be filled, and the bone defect has proper mechanical properties and physical properties to meet special application. The plastic film type skeleton type fixing material is formed by implantation, and bone tissues are reconstructed. The material can be gradually degraded after a certain time in vivo, and finally metabolized into water and carbon dioxide which are absorbed by human body and then discharged out of body.

By adopting the technical scheme, the invention better realizes the aim of the invention, the high-viscosity glue material for the non-invasive implantation of the orthopaedics is prepared by mixing the high-viscosity glue water dispersible granules with the adhesive solution and acetic acid on site, namely the high-viscosity glue solution for the non-invasive implantation of the orthopaedics is prepared, is used along with preparation, can accurately control the curing time (the curing time can be controlled to be 8 minutes), ensures that the high-viscosity glue solution is not solidified within 5 minutes after the operation implantation time, and is quickly cured at the body temperature;

PLGA and beta-TCP (bone powder) have good biocompatibility, and the PLGA and the beta-TCP (bone powder) can be prepared into porous curing materials, so that the bone tissue can grow in, the bone healing is promoted, the proliferation and the differentiation during the adhesion of chondrocytes are well induced and promoted, the cartilage tissue is formed, the bone tissue grows in and the bone healing is promoted, and no toxicity exists; poly (hydroxypropyl fumarate) (PPF) is a biodegradable material, and the material is gradually degraded and discharged from the body after new bones grow; the poly-hydroxypropyl fumarate (PPF) and the N-vinyl pyrrolidone are biodegradable, when the poly-hydroxypropyl fumarate (PPF) and the N-vinyl pyrrolidone are subjected to crosslinking reaction with a medical adhesive, high-viscosity glue water dispersible granules are added to be compounded into a sticky solution, and the sticky solution and sodium chloride are implanted into a body together and then dissolved and absorbed to form a pore channel again, so that tissues can grow in the pore channel, and the bone healing is accelerated;

the solution can be implanted in a minimally invasive injection mode, is quickly solidified at body temperature to form a plastic film-shaped film block material, and can obtain a material with good mechanical property by controlling the molecular weight of the material, and the fracture and bone disease parts can be directly and firmly fixed at the body temperature; the cross-linked reticular polymer material increases the adsorption force, thereby having the characteristic of high viscosity, simultaneously improving the reconstruction and repair strength, and forming a porous reticular firm protective film on the surface of the damaged tissue to prevent hyperplasia; the biodegradable plastic film stent has certain elasticity and rigidity (hardness), has proper mechanical and physical properties to meet special application, maintains the mechanical properties in the degradation process, has good biocompatibility of degradation products, can be degraded according to an initial shape, maintains the shape of the plastic film stent for a long time, has controllable biodegradation, and has no toxic or side effect; the implantation is realized in a minimally invasive injection mode, and the implantation mode is accurate and convenient; after being implanted, the implant can promote and regulate the growth and differentiation of cells around the periosteum, accelerate the formation of bone matrix and the biological mechanism of mineralization and promote the rapid healing of fracture; the material can be gradually degraded after a certain time in vivo, and finally metabolized into water and carbon dioxide which are absorbed by human body and then discharged out of the body;

the bone can be filled into bone defects with different shapes and sizes after open reduction of the operation, the bone defects are fixed to form a required shape, the bone defects have proper mechanical properties and physical properties, and the reconstructed bone tissue is repaired to meet special application.

Detailed Description

The present invention will be further described with reference to the following examples.

Example 1:

a non-invasive implantation high-viscosity adhesive material for orthopedics department is prepared from the following raw materials in proportion:

PLGA: beta-TCP: sodium chloride: ethyl acetate: distilled water: medical adhesive: polyhydroxypropylfumarate (PPF): n-vinyl pyrrolidone =760mg to 1520 mg: 240 mg-480 mg: 20 mg-40 mg: 8 mL-12 mL: 100 mL-200 mL: 19 mL-38 mL: 3 mL-6 mL: 3 mL-6 mL; or PLGA: beta-TCP: phosphate buffer solution: sodium chloride: distilled water: medical adhesive: polyhydroxypropylfumarate (PPF): n-vinylpyrrolidone =760mg to 1520 mg: 240 mg-480 mg: 30 mL-50 mL: 10 mg-20 mg: 100 mL-200 mL: 19 mL-38 mL: 3 mL-6 mL: 3 mL-6 mL (the ratio of the raw materials in this example is PLGA: beta-TCP: sodium chloride: ethyl acetate: distilled water: medical adhesive: poly-hydroxypropyl fumarate: N-vinyl-propyl pyrrolidone =1520 mg: 480 mg: 40 mg: 12 mL: 200 mL: 38 mL: 6 mL: 6 mL).

The PLGA ratio (molar ratio) is DL-LA/GA = 75/25;

the beta-TCP is nano-powder; the pH value of the phosphate buffer solution is 7.2.

fifthly, dissolving the medical adhesive, the poly-hydroxypropyl fumarate (PPF) and the N-vinylpyrrolidone in distilled water according to the ratio, stirring, polymerizing the medical adhesive, the poly-hydroxypropyl fumarate (PPF) and the N-vinylpyrrolidone to synthesize a sticky solution, and then performing centrifugal separation at 300 revolutions per minute to obtain an adhesive solution for later use;

sixthly, irradiating the high-viscosity adhesive water dispersible granules obtained in the step four and the adhesive solution obtained in the step fifthly with cobalt 60 for sterilization, combining and packaging according to a ratio to obtain a required specification, and storing to obtain the non-invasive implanting high-viscosity adhesive material for orthopedics department.

The solution A in the step of the invention comprises the following raw materials: beta-TCP: sodium chloride: ethyl acetate =380mg to 760 mg: 120 mg-240 mg: 10 mg-20 mg: 8 mL-12 mL (in this example, the ratio of the raw materials of the solution A is PLGA: beta-TCP: sodium chloride: ethyl acetate =760 mg: 240 mg: 20 mg: 12 mL);

the preparation method comprises the following steps that the raw material ratio of the solution C is PLGA: beta-TCP: sodium chloride: distilled water =380mg to 760 mg: 120 mg-240 mg: 10 mg-20 mg: 50 mL-100 mL (in this example, the ratio of the raw materials of the solution C is PLGA: beta-TCP: sodium chloride: distilled water =760 mg: 240 mg: 20 mg: 100 mL);

the drying in the step four is drying at 60-120 ℃ for 2-1 hour or freeze drying (in this embodiment, drying at 120 ℃ for 2 hours);

the adhesive solution in the step fifthly is prepared from the following raw materials in parts by weight: polyhydroxypropylfumarate (PPF): n-vinylpyrrolidone: distilled water =19mL to 38 mL: 3 mL-6 mL: 3 mL-6 mL: 50 mL-100 mL (in this example, the ratio of the raw materials of the adhesive solution is medical adhesive: poly hydroxy propyl fumarate: N-vinyl pyrrolidone: distilled water =38 mL: 6 mL: 6 mL: 100 mL).

The step sixteenth of the sixteenth is that the high-viscosity glue water dispersible granules are packaged and proportioned according to the combination of the non-invasively implanted high-viscosity glue material used by the orthopedic department: adhesive solution = 5-10 g/bottle (penicillin bottle): 25-50 mL/bottle (in this example, high viscosity glue water dispersible granule: glue solution =5 g/bottle: 25 mL/bottle).

An orthopedic noninvasive implantation high-viscosity adhesive material is applied to operations for treating fractures, bone diseases and bone tumors (or in operation open bone filling), organic acid solvents and adhesive solutions which have no toxic or side effect on a human body are sequentially added into high-viscosity adhesive water dispersible granules according to a proportion to be dissolved, poly hydroxypropyl fumarate (PPF) and N-vinyl pyrrolidone are biodegradable and are crosslinked with medical adhesives, and the high-viscosity adhesive water dispersible granules and acetic acid are added to be compounded into viscous suspension liquid solutions, so that the orthopedic noninvasive implantation high-viscosity adhesive solution is obtained.

The organic acid solvent in the application of the invention is acetic acid.

The dissolution proportion in the application of the invention is high-viscosity glue water dispersible granules: adhesive solution: acetic acid =5 g: 25mL of: 0.5 mL.

Example 2:

the non-invasive implantation high-viscosity glue material for orthopedics department is prepared from the following raw materials in parts by weight:

PLGA: beta-TCP: sodium chloride: ethyl acetate: distilled water: medical adhesive: polyhydroxypropylfumarate (PPF): n-vinyl pyrrolidone =760 mg: 240 mg: 20 mg: 8mL of: 100mL of: 19mL of: 3mL of: 3 mL.

The preparation method of the non-invasive implantation high-viscosity glue material for orthopedics in the embodiment comprises the following steps of: beta-TCP: sodium chloride: ethyl acetate =380 mg: 120 mg: 10 mg: 8 mL;

the preparation method comprises the following steps that the raw material ratio of the solution C is PLGA: beta-TCP: sodium chloride: distilled water =380 mg: 120 mg: 10 mg: 50 mL;

the drying in the step four is drying for 1 hour at 120 ℃;

the adhesive solution in the step fifthly is prepared from the following raw materials in parts by weight: polyhydroxy-propyl polyfumarate: n-vinylpyrrolidone: distilled water =19 mL: 3mL of: 3mL of: 50 mL.

The step sixteenth is that the bone department implants the high-viscosity adhesive material in a noninvasive mode, and the high-viscosity adhesive water dispersible granules are packaged and proportioned according to the following steps: adhesive solution =5 g/bottle: 25 mL/bottle.

The same as in example 1.

Example 3:

PLGA: beta-TCP: sodium chloride: ethyl acetate: distilled water: medical adhesive: polyhydroxypropylfumarate (PPF): n-vinyl pyrrolidone =1520 mg: 400 mg: 40 mg: 10mL of: 100mL of: 38mL of: 6mL of: 6 mL.

The preparation method of the non-invasive implantation high-viscosity glue material for orthopedics in the embodiment comprises the following steps of: beta-TCP: sodium chloride: ethyl acetate =760 mg: 200 mg: 20 mg: 10 mL;

the step two is that the raw material ratio of the solution C is PLGA: beta-TCP: sodium chloride: distilled water =760 mg: 200 mg: 20 mg: 50 mL;

the drying in the step four is drying for 2 hours at 120 ℃;

the adhesive solution in the step fifthly comprises the following raw materials in parts by weight: polyhydroxy-propyl polyfumarate: n-vinylpyrrolidone: distilled water =38 mL: 6mL of: 6mL of: 50 mL.

The step sixteenth is that the bone department implants the high-viscosity adhesive material in a noninvasive mode, and the high-viscosity adhesive water dispersible granules are packaged and proportioned according to the following steps: adhesive solution =10 g/bottle: 50 mL/bottle.

The same as in example 2.

Example 4:

PLGA: beta-TCP: phosphate buffer solution: sodium chloride: distilled water: medical adhesive: polyhydroxy-propyl polyfumarate: n-vinylpyrrolidone =760 mg: 240 mg: 30mL of: 20 mg: 200mL of: 19mL of: 3mL of: 3 mL.

The preparation method of the non-invasive implantation high-viscosity adhesive material for orthopedics includes the steps of dissolving PLGA and beta-TCP in a phosphate buffer solution to obtain a solution B for later use; the solution B is prepared from PLGA: beta-TCP: phosphate buffer =380 mg: 120 mg: 30 mL.

The step in this embodiment is in the middle of solution C's raw materials ratio is PLGA: beta-TCP: sodium chloride: distilled water =380 mg: 120 mg: 20 mg: 100 mL;

the drying in the step four is freeze drying;

the adhesive solution in the step fifthly is prepared from the following raw materials in parts by weight: polyhydroxy-propyl polyfumarate: n-vinylpyrrolidone: distilled water =19 mL: 3mL of: 3mL of: 100mL, and stirring at 7 ℃.

The same as in example 1.

Example 5:

PLGA: beta-TCP: sodium chloride: ethyl acetate: distilled water: medical adhesive: polyhydroxypropylfumarate (PPF): n-vinyl pyrrolidone =1000 mg: 480 mg: 30 mg: 12mL of: 180 mL: 28mL of: 4mL of: 4 mL.

The preparation method of the non-invasive implantation high-viscosity glue material for orthopedics in the embodiment comprises the following steps of: beta-TCP: sodium chloride: ethyl acetate =500 mg: 240 mg: 15 mg: 12 mL;

the preparation method comprises the following steps that the raw material ratio of the solution C is PLGA: beta-TCP: sodium chloride: distilled water =500 mg: 240 mg: 15 mg: 90 mL;

the drying in the step four is drying for 2 hours at 120 ℃;

the adhesive solution in the step fifthly is prepared from the following raw materials in parts by weight: polyhydroxy-propyl polyfumarate: n-vinylpyrrolidone: distilled water =28 mL: 4mL of: 4mL of: 90 mL.

The step sixteenth is that the bone department implants the high-viscosity adhesive material in a noninvasive mode, and the high-viscosity adhesive water dispersible granules are packaged and proportioned according to the following steps: adhesive solution =8 g/bottle: 45 mL/bottle.

The same as in example 3.

Example 6:

PLGA: beta-TCP: phosphate buffer solution: sodium chloride: distilled water: medical adhesive: polyhydroxy-propyl polyfumarate: n-vinylpyrrolidone =1520 mg: 480 mg: 50mL of: 15 mg: 180 mL: 38mL of: 6mL of: 6 mL.

The preparation method of the non-invasive implanting high-viscosity glue material for orthopedics comprises the following steps of mixing PLGA: beta-TCP: phosphate buffer =760 mg: 240 mg: 50 mL.

The step in this embodiment is in the middle of solution C's raw materials ratio is PLGA: beta-TCP: sodium chloride: distilled water =760 mg: 240 mg: 15 mg: 90 mL;

the drying in the step four is freeze drying;

the adhesive solution in the step fifthly is prepared from the following raw materials in parts by weight: polyhydroxy-propyl polyfumarate: n-vinylpyrrolidone: distilled water =38 mL: 6mL of: 6mL of: 90 mL.

The same as in example 4.

Example 7:

PLGA: beta-TCP: phosphate buffer solution: sodium chloride: distilled water: medical adhesive: polyhydroxy-propyl polyfumarate: n-vinylpyrrolidone =1500 mg: 450 mg: 40mL of: 10 mg: 100mL of: 22.8 mL: 4mL of: 4 mL.

The preparation method of the non-invasive implantation high-viscosity glue material for orthopedics in the embodiment comprises the following steps of: beta-TCP: phosphate buffer =750 mg: 225 mg: 40 mL.

The step in this embodiment is in the middle of solution C's raw materials ratio is PLGA: beta-TCP: sodium chloride: distilled water =750 mg: 225 mg: 10 mg: 50 mL;

the drying in the step four is freeze drying;

the adhesive solution in the step fifthly is prepared from the following raw materials in parts by weight: polyhydroxy-propyl polyfumarate: n-vinylpyrrolidone: distilled water =22.8 mL: 4mL of: 4mL of: 50 mL.

The same as in example 4.

Test examples

Test (1): healing action and Properties

It is quick-witted that it makes mould and grouping of clamp dose

Selecting 110 rabbits with the weight of 1.6-2.0 kg; then randomly divided into 5 groups of 22;

(A) as blank control group: 10mL/kg of physiological saline, wherein (B) to (E) are respectively embodiments 1 to 4 of the invention, and the non-invasive implantation high-viscosity glue material for orthopedics department is dissolved by 0.083g/kg of high-viscosity glue water dispersible granules, 0.417mL/kg of adhesive solution and 0.0417mL/kg of acetic acid;

using a steel saw to perform a 3mm defect operation on the left radius of the fracture by interruption and crossing, respectively injecting normal saline or tested drugs at the fracture end according to dosage design, and carefully observing the rabbit wound and the activity condition of the left forelimb continuously for 3 weeks;

observation of catalyst component of a polymer

First, the influence on the time, number and calcification of callus appearance: the 5 groups of animals were subjected to first, second, third and fourth X-ray films after the operation under the same conditions. The bone fracture is characterized in that the bone fracture is divided into two parts, namely a fracture edge and a fracture edge, wherein the bone fracture edge is divided into two parts, namely a bone fracture edge and a fracture edge, the bone fracture edge is divided into two parts, the bone fracture edge is divided into two bone fracture edges, the bone fracture edge is divided into two bone fracture edges, the bone edges are divided into two bone edges, the bone edges are divided bone edges, the bone edges are divided into two bone edges, the bone edges are divided into two bone edges, the bone edges are divided edges, the bone edges are divided edges, the bone edges are divided into two bone edges, the bone edges are divided into two bone edges, the bone edges are divided edges, the bone edges are divided into two bone edges, the bone edges are divided into two bone edges, the bone edges are divided edges, the bone edges are divided into two bone edges.

TABLE I Effect of the invention on callus formation

Table I shows that more callus with more than medium and equal amount appears in the group of the invention in the second week, most fracture edges disappear in the third week, the proportion of the fracture edges completely connected into normal bone is large, most fracture lines disappear in the fourth week, the fracture healing is good, and the effect of promoting the fracture healing of the invention is obvious.

The influence on the biomechanics is as follows: 6 patients are randomly sampled and killed in the first, second, third and fourth postoperative groups, the left total radius is taken, and the fracture strength of the radius shaft is tested by a hydraulic universal tester.

TABLE II Effect of the invention on the flexural Strength of the backbone (unit: kg)

Table II shows that the group of the present invention has a greatly increased flexural strength, especially almost three times as much as the latter strength at the final stage of fracture healing, and has high rigidity and hardness after fracture healing, compared with the blank group.

Performing histological observation: after the fracture strength is measured, the samples with the callus are taken, fixed by 10 percent formaldehyde and sent to pathological examination.

Obvious fibrous callus appears in each group of the invention in the first week, and new bone trabecula can be seen at the broken end of the fracture;

no obvious callus connection is seen in the A level in the second week, other callus groups are continuously connected with the fracture broken ends, and osteoblasts and cartilage hyperplasia are active;

the trabeculae of the group A are slightly thickened and enlarged in the third week, and the trabeculae of other groups are thickened and enlarged;

the trabecular bone in the B, C, D, E th week was significantly thickened and enlarged, however, the formation of osteoblasts and cartilage in the blank group was reduced in the first two weeks, and the morphological changes in each phase were at least one week slower than the healing process of the fracture according to the present invention.

The experiments prove that the invention has the advantages of shortening the fracture healing time, enhancing the fracture strength and better promoting the fracture healing.

Test (2): sticking and fixing time and fixing effect

Sampling specimen with driving device

Firstly, 1 sheep rib is taken, mutton and periosteum are removed, and the rib is complete and has no defect.

The length is 23cm, the intermediate width is 2cm, the thickness is 1.3cm, and the net weight is 26 g.

Cutting the sheep rib into three sections by a steel knife, and artificially causing the transverse fracture of the sheep rib; the fracture site at the near end is 3cm away from the adjacent joint at the one end, and the fracture site at the far end is 5cm away from the joint at the other end (namely, the three-section fracture lengths are respectively 3cm for the fracture site at the near end, 15 cm for the middle bone and 5cm for the fracture site at the far end); the width of the proximal fracture part is 2.5cm, and the thickness is 1.3 cm; the width of the fracture part at the far end is 2cm, and the thickness is 1.2 cm;

putting into a porcelain basin with the number of No. 1 for standby.

② 2 pig ribs are taken, pork and periosteum are removed, and the ribs are complete and have no defect.

Respectively 29.5 cm in length, 6 cm in ambient diameter and 50.18 g in net weight; the length is 25 cm, the surrounding diameter is 5.6 cm, and the net weight is 31.56 g;

the method is characterized in that a steel saw is used for sawing one pig rib (close to the spine when the pig is in the original pig body) into two sections (namely, the section of proximal fracture is 10 cm, the section of distal fracture is 19.5 cm), the transverse fracture of the pig rib is artificially caused, and the number is No. 2 for later use;

the pig rib fracture is sawed into two sections at the position 12 cm near the joint of another pig rib by using a steel saw, and the crushed pig rib fracture is artificially caused and is numbered as No. 3 for later use.

Method of capsule wall processing and dosing

Firstly, pouring 5g of high-viscosity glue water dispersible granules into a vessel, adding 0.5mL of acetic acid, uniformly mixing with a glass rod, adding 25mL of adhesive solution, and further uniformly mixing to obtain the noninvasive high-viscosity glue solution for orthopedics, and then quickly implanting into the fractured bone cortex of the No. 1 sample.

The proximal (proximal fracture) broken end of sample No. 1 was fixed only on the dorsal side, with an implant dose of 1.3g, and no material was implanted on the ventral side (convex side of rib is dorsal side, concave side is ventral side); the material was implanted all around the distal (distal fracture) fracture site at an implant dose of 2.7g, and the net weight of sample No. 1 after fixation (second fixation) was 31 g.

And secondly, respectively taking 5g of high-viscosity glue water dispersible granules, pouring the high-viscosity glue water dispersible granules into a vessel, adding 0.5mL of acetic acid, uniformly mixing the granules with a glass rod, adding 25mL of adhesive solution, further uniformly mixing the mixture to obtain the noninvasive implantation high-viscosity glue solution for orthopedics, and rapidly implanting the solution into the bone cortex of the fractured bone of the No. 2 sample and the No. 3 sample within 8 minutes.

The No. 2 sample is implanted on the back side and two sides (two side surfaces in the thickness direction of the pig rib) of the fracture broken end, and the implantation dose is 2 g; the No. 3 sample is implanted on the dorsal side and both sides of the fractured end of the fracture, and the implantation dose is 3 g.

⒊ results

Firstly, a sample I is implanted at the room temperature of 15 ℃ and then is timed, the sample I is immediately placed in a porcelain basin at the time of 3 minutes, the suspended distance between the middle parts of the fracture is 2.5cm, and the following are observed: the broken ends of the two bones are not loosened, and the proximal ends of the fractures are fixed only on the back side and are not loosened;

after 2 minutes of standing in the pot (5 minutes of cumulative implantation time) the middle bone segment was left suspended in the air and observed: the two broken ends have no crack and loose;

after 1 minute of suspension (6 minutes of cumulative implantation time) the median bone segment was lifted laterally and observed: the broken ends of the two parts of the fracture are not loosened;

after the bone fracture is transversely held for 2 minutes (the accumulated implantation time is 8 minutes), the bone marrow outside the fracture adhesion nodule is upwards implanted from the back side (convex surface) of the proximal end (2 cm) of the proximal fracture part, and the following observations are made: the fracture end is not loosened, and the fracture end is not loosened at the far end (3 cm) away from the far end of the fracture and is firmly fixed;

after 2 minutes (cumulative implantation time 10 minutes) the sample was inverted to bring the dorsal side of the cortical bone down, hold the proximal end of the fracture, and rock up and down tens of times, observed: the fracture end has no looseness and is firmly fixed;

cumulative implantation time 24 hours, it was observed that: the fracture end is not abnormally loosened, the fracture is firmly fixed, and the proximal end is fixed at the back side without loosening;

from a 2m high throw, it was observed that: the fracture end has no looseness and fracture, the proximal end only fixes the bone on the dorsal side and has no looseness, and the bone cortex on the dorsal side of the fracture can also play a role in firm fixation.

Secondly, the second sample and the third sample are implanted at the room temperature of 20 ℃ and then are timed, and the fracture distal end is transversely hung in the air at 3 minutes and observed: the fracture is not loosened and is firmly fixed;

at 5 minutes of implantation, it was observed that: the fracture is fixed, the fracture is not loosened and is firmly fixed;

after 24 hours of implantation, it was observed that: the fracture ends are firmly fixed and completely cured.

And (4) conclusion:

1. the invention is suitable for minimally invasive implantation treatment of traumatic fracture and other (pathological fracture and osteoporotic fracture) bone tumors (benign bone tumors).

2. The fracture adhesion part can be simultaneously implanted with materials at the back side and two sides of the fracture for satisfactory fixation, and is equal to the fixation of the implanted materials of the sheep rib fracture far-end periphery, the pig rib transverse fracture and the comminuted fracture. It is proved that 1.2g of material is implanted into the proximal fracture end of the sheep rib, the fixation part is the dorsal side of the bone, the ventral side is not implanted with the material, and 2.7g of material is implanted into the distal end, and the bonding strength (hardness) is equivalent in the test. The two different parts are implanted with different materials in 24 hours, the two fractures are not loosened and fractured when the patient is thrown at 2m high altitude, and the external fixation is carried out on the limbs after the minimally invasive surgery is completed, so that the material is considered to meet the requirements of clinical tests, but the trial material of a No. three sample of a pig rib is 3g, and the material applied to the comminuted fracture is proved to be increased by 33 percent compared with the material applied to the transverse fracture. The strength (hardness) of the fracture fixation bond measured within 24 hours was both comparable. It is also considered that, in order to protect the ventral surface of the bone from damage to the large vascular nerve due to implantation, the bone may be fixed by implanting a material on the dorsal side of the fracture. Thus, the high viscosity and good moldability of the present invention were demonstrated.

3. The invention is suitable for minimally invasive implantation to treat various fractures, osteoporotic fracture and creative fracture (far bone fracture, double ankle fracture, finger fracture, toe fracture and the like) of the old.

4. The product is shown by material analysis research and animal test combination: the material can be quickly agglutinated and fixed in 3-5 minutes under the action of body temperature when entering the body, is stable in fracture, is cured within 10-12 hours, is completely cured within 24 hours, and can effectively control fracture displacement or loosening.

5. The invention has stable storage property, and the fracture fixation is firm after ten minutes at room temperature of 15 ℃ in an in vitro bonding fixation test of the sheep ribs. The external adhesion fixation test of the pig rib is carried out at the room temperature of below 20 ℃, and the time interval from the configuration of the operation space for obtaining the noninvasive implanting high-viscosity glue solution for orthopaedics to the implantation of the pig rib is 8 minutes. Is convenient for preparation and implantation in the operation field.

Claims

1. A preparation method of a non-invasive implantation high-viscosity adhesive material for orthopedics department is characterized by comprising the following steps:

the preparation method comprises the steps of dissolving PLGA, beta-TCP and sodium chloride in ethyl acetate according to a ratio to obtain a solution A;

fourthly, carrying out centrifugal separation on the product obtained in the third step at 1000 revolutions per minute, washing with water, drying to obtain high-viscosity glue ultrafine particle powder, adding distilled water with required amount, dispersing uniformly, and packaging to obtain the high-viscosity glue water dispersible granule;

fifthly, dissolving the medical adhesive, the poly-hydroxypropyl fumarate and the N-vinylpyrrolidone in distilled water according to the ratio, stirring to obtain a sticky solution, and then performing centrifugal separation at 300 revolutions per minute to obtain an adhesive solution for later use;

sixthly, irradiating the high-viscosity adhesive water dispersible granules obtained in the step four and the adhesive solution obtained in the step fifthly with cobalt 60 for sterilization, and packaging the components according to a ratio to obtain a required specification for storage, so as to obtain the noninvasive implantation high-viscosity adhesive material for orthopedics;

the PLGA: beta-TCP: sodium chloride: ethyl acetate: distilled water: medical adhesive: polyhydroxy-propyl polyfumarate: n-vinylpyrrolidone =760mg to 1520 mg: 240 mg-480 mg: 20 mg-40 mg: 8 mL-12 mL: 100 mL-200 mL: 19 mL-38 mL: 3 mL-6 mL: 3mL to 6mL, or PLGA: beta-TCP: phosphate buffer solution: sodium chloride: distilled water: medical adhesive: polyhydroxy-propyl polyfumarate: n-vinylpyrrolidone =760mg to 1520 mg: 240 mg-480 mg: 30 mL-50 mL: 10 mg-20 mg: 100 mL-200 mL: 19 mL-38 mL: 3 mL-6 mL: 3 mL-6 mL;

the PLGA ratio is DL-LA/GA = 75/25; the pH value of the phosphate buffer solution is 7.2.

2. The preparation method of the non-invasive implantation high-viscosity adhesive material for orthopedics department according to the claim 1, is characterized in that:

the solution A in the step is prepared from the following raw materials in percentage by weight: beta-TCP: sodium chloride: ethyl acetate =380mg to 760 mg: 120 mg-240 mg: 10 mg-20 mg: 8 mL-12 mL;

the solution B is prepared from the following raw materials in percentage by weight: beta-TCP: phosphate buffer =380mg to 760 mg: 120 mg-240 mg: 30 mL-50 mL;

the adhesive solution in the step fifthly is prepared from the following raw materials in parts by weight: polyhydroxy-propyl polyfumarate: n-vinylpyrrolidone: distilled water =19mL to 38 mL: 3 mL-6 mL: 3 mL-6 mL: 50 mL-100 mL;

the step sixteenth is that the bone department implants the high-viscosity adhesive material in a noninvasive mode, and the high-viscosity adhesive water dispersible granules are packaged and proportioned according to the following steps: adhesive solution = 5-10 g/bottle: 25-50 mL/bottle.

3. The application of the noninvasive implantable high-viscosity glue material for orthopedics obtained by the preparation method of the noninvasive implantable high-viscosity glue material for orthopedics as claimed in claim 1 or 2 is characterized in that an organic acid solvent and an adhesive solution are sequentially added into the high-viscosity glue water dispersible granules according to a proportion for dissolution to obtain the noninvasive implantable high-viscosity glue solution for orthopedics; the organic acid solvent is acetic acid; the dissolution proportion is high-viscosity glue water dispersible granules: adhesive solution: acetic acid =5 g: 25mL of: 0.5 mL.