CN114917416A

CN114917416A - Absorbable anti-adhesion material and preparation method thereof

Info

Publication number: CN114917416A
Application number: CN202210557287.2A
Authority: CN
Inventors: 胡方; 王晓朋
Original assignee: Beijing Best Life Regenerative Medicine Technology Co ltd
Current assignee: Beijing Best Life Regenerative Medicine Technology Co ltd
Priority date: 2022-05-20
Filing date: 2022-05-20
Publication date: 2022-08-19
Also published as: CN115444992A

Abstract

The invention relates to the technical field of biomedical materials, and provides an absorbable anti-adhesion material and a preparation method thereof. The absorbable anti-adhesion material comprises: the active ingredients of the antibacterial and anti-inflammatory layer A comprise degradable and absorbable high molecular materials of a human body, a plasticizer, a bioactive mineral material, antibacterial and anti-inflammatory ingredients and trace element stock solution; and/or the anti-adhesion layer B, wherein the active ingredients of the anti-adhesion layer B comprise degradable and absorbable high molecular materials of human bodies, plasticizers, bioactive mineral materials and trace element stock solution. The absorbable anti-adhesion material has larger specific surface area, forms a three-dimensional reticular structure after contacting with body fluid, is beneficial to the proliferation and climbing of cells, guides the differentiation of the cells, leads tissues to be tightly combined, can accelerate the healing of wounds and effectively prevents the adhesion of the tissues after the wound surface is repaired. The absorbable anti-adhesion material provided by the invention integrates the advantages of antibiosis, anti-inflammation, acceleration of wound healing, controllable degradation, safety, no stimulation and the like, and provides a multifunctional anti-adhesion material.

Description

Absorbable anti-adhesion material and preparation method thereof

Technical Field

The invention relates to the technical field of biomedical materials, in particular to an absorbable anti-adhesion material and a preparation method thereof.

Background

Postoperative adhesion is a ubiquitous problem in the field of surgical operations and one of the medical problems which have not been solved for a long time in the clinic. Almost all clinical operations involve the problems of adhesion prevention and local anti-inflammation among tissues, and the tissue adhesion generated after the surgical operations of the abdomen, the cardiovascular system, the spine, the bone joint, the legs, the gynecological pelvic cavity and the like of a human body not only brings great pain to patients, but also causes great economic loss; postoperative adhesions can also cause serious complications such as intestinal obstruction, chronic pain, ectopic pregnancy, infertility, etc., increase the chance of secondary operations, and even lead to death.

Infection is one of many factors causing postoperative adhesion, most of the previous researches neglect the influence of bacterial infection on adhesion formation, especially on abdominal cavity adhesion, and because a wound surface is exposed in a humid environment rich in a large amount of abdominal cavity liquid, the probability of bacterial infection is greatly improved, and the incidence rate of postoperative adhesion is increased. For example, exudate resulting from E.coli infection contains a large amount of fibrin and leukocytes, which leads to the formation of tight adhesions.

So far, the antiblocking materials can be roughly classified into three generations. The first generation is mechanical materials which are not degradable and absorbable by human body, such as metal, silk, rubber and the like; the second generation materials are barrier materials which are difficult to absorb by human bodies, such as mineral oil and the like; the third generation material is a biological material which can be degraded and absorbed by human body, such as hyaluronic acid, polylactic acid, polysaccharide substance, etc. Among them, the third generation biomaterials are widely used in clinical practice.

Collagen is an important structural protein with functions of supporting organs and protecting organisms, is a main component of connective tissues in dermis, accounts for more than 75% of the dermis layer of skin, and forms a protective net on the outermost layer of a human body. Collagen has early application in skin wound repair, but the defect of collagen as artificial skin is that the physical and mechanical properties are poor, and in a human body environment rich in enzyme and microenvironment, a collagen membrane material is easy to carry out enzymolysis, so that the failure of an operation is finally caused, and the clinical application of the collagen is limited. The collagen dressing has good biocompatibility, has the effects of stopping bleeding, promoting coagulation and promoting cell division and differentiation, but has weak stability, poor elasticity, crisp texture and water resistance, is derived from animals and has the risk of infection.

Chitosan, also known as chitosan, has obvious effects of promoting wound contraction and healing, and is an implant material with excellent biological properties and great development potential. However, the adhesion and degradation rate of chitosan are controlled, and the problems of inflammation and foreign body reaction in the early stage of implantation are mostly remained in the experiment and the clinical application in a small range.

Hyaluronic acid is a natural component of human connective tissue and has good biocompatibility. However, hyaluronic acid has a short residence time in the body, and thus cannot maintain a high drug concentration on the wound surface for a long time, and thus the anti-adhesion effect is affected, and many studies have focused on the combined use of hyaluronic acid with other high molecular polymers.

The carboxymethyl cellulose is one of cellulose ethers, and as a novel organic anti-adhesion material, the carboxymethyl cellulose can obviously reduce the formation of abdominal adhesion and also has certain hemostatic effect. The carboxymethyl cellulose can be prepared into various forms such as solution, gel and the like, and has the characteristics of good absorbability, no toxicity, no immunogenicity, good biocompatibility and the like. The single carboxymethyl cellulose has good film forming property, but is very soluble in water, and after a period of time in the water, a good film structure cannot be kept, the mechanical property is poor, the tensile strength is low, and the degradation speed is too high.

Chinese patent 201811112155.9 discloses an anti-adhesion hemostatic dressing and a preparation method thereof, the anti-adhesion hemostatic dressing comprises an adsorbed gauze substrate and an anti-adhesion hemostatic composition, the anti-adhesion hemostatic composition comprises hydroxymethyl chitosan and hyaluronic acid, the degradation period of the anti-adhesion hemostatic composition is adjustable, the space is small, and the anti-adhesion effect is to be improved.

In conclusion, an absorbable anti-adhesion material with antibacterial, anti-inflammatory, wound healing accelerating and degradation controllable functions is currently and clinically lacked.

Disclosure of Invention

In view of the above-mentioned disadvantages of the prior art, the present invention aims to provide an absorbable anti-blocking material and a method for preparing the same.

In order to realize the purpose, the invention adopts the technical scheme that:

an absorbable adhesion-prevention material, comprising:

the active ingredients of the antibacterial and anti-inflammatory layer A comprise degradable and absorbable high molecular materials of a human body, a plasticizer, a bioactive mineral material, antibacterial and anti-inflammatory ingredients and trace element stock solution;

and/or the anti-adhesion layer B, wherein the active ingredients of the anti-adhesion layer B comprise degradable and absorbable high molecular materials of human bodies, plasticizers, bioactive mineral materials and trace element stock solution.

In the absorbable anti-blocking material, as a preferred embodiment, the mass ratio of the active ingredients of the antibacterial and anti-inflammatory layer a is that the mass ratio of the human body degradable and absorbable high molecular material: plasticizer: bioactive mineral material: antibacterial and anti-inflammatory components: 1: (0.1-10): (0.01-10): (0.9-15): (0-10) (e.g., 1:3:1:1:1, 1:1:3:1:3, 1:1:3:1:5, 1:1:1:3:9, 1:3:1:1:1, 1:5:1:1, 1:1:5:1:3, 1:1:5:1:5, 1:1:1:5:9, 1:7:1:1:1, 1:1:7:1:3, 1:1:7:1:5, 1:1:1:7:9, 1:1:1:13: 9); the mass ratio of active ingredients of the anti-adhesion layer B is that the anti-adhesion layer B is made of a human degradable and absorbable high polymer material: plasticizer: bioactive mineral material: the microelement stock solution is 1: (0.1-10): (0.01-10): (0-10) (e.g., 1:1:1:1, 1:1:1:3, 1:1:1:5, 1:1:1:7, 1:1:1:9, 1:3:1:1, 1:1:3:3, 1:5:1:5, 1:1:5:7, 1:9:3: 9).

In the absorbable anti-adhesion material, as a preferred embodiment, the human body degradable and absorbable polymer material comprises: one or more of hyaluronic acid and derivatives thereof, cellulose ether and derivatives thereof, chitosan and derivatives thereof, and starch and derivatives thereof; preferably, the human degradable and absorbable polymer material comprises: one or more of hyaluronic acid, sodium hyaluronate, carboxymethyl cellulose, sodium carboxymethyl cellulose, chitosan and starch.

In the foregoing absorbable material for preventing adhesion, As a preferred embodiment, the elemental starting solution includes boron (B), iron (Fe), potassium (K), magnesium (Mg), manganese (Mn), sodium (Na), phosphorus (P), titanium (Ti), silicon (Si), aluminum (Al), lithium (Li), beryllium (Be), scandium (Sc), vanadium (V), chromium (Cr), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), gallium (Ga), germanium (Ge), arsenic (As), selenium (Se), (Rb), strontium (Sr), yttrium (Y), zirconium (Zr), niobium (Nb), molybdenum (Mo), silver (Ag), cadmium (Cd) and indium (In).

In the invention, the microelement stock solution is a high-energy multifunctional water-containing complex ion group concentrated solution with micro magnetic moment, and has stronger sterilization and disinfection effects; the described microelement stock solution contains 20 kinds of life-related elements and water-containing complex cation group of life power element, in which the electron transfer free radical reaction of several transition elements can automatically produce hydroxyl free radical [. OH ], and possesses strong oxidation action, its oxidation potential is far higher than that of other oxidant, and is one time higher than that of chlorine, and it can break various chemical bonds, specially has the function of oxidative cracking for active bond of toxic structure, and possesses strong sterilization and disinfection function. In addition, the organic trace elements permeate through the skin, and can participate in cell metabolism and promote skin growth. The microelement stock solution used by the invention is produced by Beijing Jinshan ecological power element manufacturing limited company, the trade name of the microelement stock solution is the life power element, and the academic name of the microelement stock solution is the metal ion linear condensed state magnetized mineral solution.

In the absorbable anti-adhesion material, the bioactive mineral material is an inorganic compound containing silicon, phosphorus and oxygen; as a preferred embodiment, the bioactive mineral material comprises one or more of bioactive glass, Regesi regenerated silica, hydroxyapatite, phosphosilicate and its derivatives, silicate and its derivatives, and phosphate and its derivatives.

The RegeSi regenerated silicon mentioned in the invention is according to the application publication number: CN111017934A, the method of Chinese patent. The RegeSi regenerated silicon comprises: the calcium phosphate silicate compound comprises a bracket with a porous structure formed by stacking nano-scale silicon dioxide particles, and calcium and phosphorus elements uniformly distributed in the bracket, wherein the calcium phosphate compound is a calcium phosphate silicate compound with biological activity; the specific surface area of the regenerated silicon is 200-350 square meters per gram; the corresponding commercial product is regenerated silicon produced by Happy Probiotics and regenerative medicine science and technology Limited.

In the above absorbable anti-blocking material, as a preferred embodiment, when the absorbable anti-blocking material comprises the antibacterial anti-inflammatory layer a and the anti-blocking layer B, the antibacterial anti-inflammatory layer a is attached to one side or both sides of the anti-blocking layer B; or the anti-adhesion layer B is attached to one side or two sides of the antibacterial and anti-inflammatory layer A.

In the absorbable adhesion-preventing material described above, as a preferred embodiment, when the antibacterial/anti-inflammatory layer a is attached to one or both sides of the adhesion-preventing layer B, the mass content of the bioactive mineral material in the antibacterial/anti-inflammatory layer a is lower than the mass content of the bioactive mineral material in the adhesion-preventing layer B.

In the invention, the antibacterial and anti-inflammatory components in the antibacterial and anti-inflammatory layer play a main role, and the bioactive mineral material has small addition amount and plays an auxiliary role; according to the invention, the addition amount of the bioactive mineral material in the anti-adhesion layer B in the AB or ABA double-layer structure is preferably large, the repair promoting effect is gradually increased layer by layer and enhanced layer by layer, and the situation that the organism is not tolerant due to too much addition amount of the bioactive mineral material at one time is avoided. When the anti-blocking material is prepared in a gel form, the gel-form anti-blocking material has a reduced effect of absorbing the permeation solution (i.e., a reduced water absorption) and does not have a gradual progressive effect.

In the above absorbable anti-blocking material, as a preferred embodiment, the arrangement structure type of each layer in the absorbable anti-blocking material is: A. b, AB, ABA or BAB.

In the absorbable material, the average pore diameter of the antibacterial and anti-inflammatory layer A is preferably 20 to 500 μm (for example, 50 μm, 100 μm, 150 μm, 200 μm, 250 μm, 300 μm, 350 μm, 400 μm, 450 μm).

In the absorbable anti-blocking material, as a preferred embodiment, the thickness of the antibacterial and anti-inflammatory layer A is 0-10mm (e.g., 1mm, 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm), and the tensile strength is 10-300N/cm (e.g., 30N/cm, 60N/cm, 90N/cm, 150N/cm, 200N/cm, 250N/cm).

In the absorbable anti-blocking material, as a preferred embodiment, the antibacterial and anti-inflammatory component of the antibacterial and anti-inflammatory layer a comprises: one or more of antibiotic anti-inflammatory component, Chinese medicinal extract and quaternary ammonium salt antibacterial component.

In the absorbable anti-adhesion material, as a preferred embodiment, the antibiotic anti-inflammatory component is one or more of β -lactam antibiotics, aminoglycoside antibiotics, quinolone antibiotics, and macrolide antibiotics.

In the absorbable anti-adhesion material, as a preferred embodiment, the Chinese medicinal extract is one or more of extracts of coptis chinensis, bezoar, scutellaria baicalensis, phellodendron amurense, honeysuckle and forsythia suspensa.

In the above absorbable anti-blocking material, as a preferred embodiment, the quaternary ammonium salt antibacterial component is a quaternary ammonium salt of an aminopolysaccharide and/or a quaternary ammonium salt of chitosan.

In the absorbable anti-blocking material, the average pore diameter of the anti-blocking layer B is preferably in the range of 20 to 500 μm (e.g., 50 μm, 100 μm, 150 μm, 200 μm, 250 μm, 300 μm, 350 μm, 400 μm, 450 μm).

The average pore size in the present invention refers to the average pore size of each void formed on the lyophilized sponge. The smaller the pore diameter is, the more compact the structure is, the higher the water absorption rate is, and the wound dressing can be used for wounds with high exudate; conversely, it is suitable for low-exudative wound. The pore size mainly depends on the type and addition amount of the degradable and absorbable high molecular material of the human body.

Among the above absorbable anti-blocking materials, as a preferred embodiment, the anti-blocking layer B has a thickness of 0 to 10mm (e.g., 1mm, 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm) and a tensile strength of 10 to 300N/cm (e.g., 30N/cm, 60N/cm, 90N/cm, 150N/cm, 200N/cm, 250N/cm).

The human degradable and absorbable high polymer materials in the antibacterial and anti-inflammatory layer A and the anti-adhesion layer B capable of promoting wound healing can adjust the degradation time of products in human bodies through different types and molecular weights of the high polymer materials, and the degradation time is adjusted according to the requirements of different wound parts.

The bioactive mineral materials in the antibacterial and anti-inflammatory layer A and the anti-adhesion layer B capable of promoting wound healing can be sintered at high temperature to adjust the retention time of the bioactive mineral materials in organisms.

In the above absorbable adhesion-preventing material, as a preferred embodiment, the absorbable adhesion-preventing material degrades in vivo for a period of 3 days to 2 years (e.g., 5 days, 10 days, 1 month, 3 months, 6 months, 9 months, 12 months, 18 months).

The preparation method of the absorbable anti-adhesion material comprises the following steps:

(a) dissolving degradable and absorbable high polymer material in water according to the dosage proportion of the active ingredients in the anti-adhesion layer B in the absorbable anti-adhesion material, and then adding a plasticizer, a bioactive mineral material and a trace element stock solution to prepare a first solution group;

(b) dissolving degradable and absorbable high polymer material of a human body with water according to the dosage proportion of the active ingredients in the antibacterial and anti-inflammatory layer A in the absorbable anti-adhesion material, and then adding a plasticizer, a bioactive mineral material, a trace element stock solution and the antibacterial and anti-inflammatory ingredients to prepare a second solution group;

(c) preparing an absorbable anti-adhesion material:

type A: pouring the second solution group into a mold, freezing and condensing to be solid, then vacuumizing, and freezing and drying to be spongy, so as to obtain an A-type absorbable anti-adhesion material;

type B: pouring the first solution group into a mold, freezing and condensing to be solid, then vacuumizing, and freezing and drying to be spongy, so as to obtain a B-type absorbable anti-adhesion material;

AB and ABA types: pouring the first solution group into a mold, freezing and condensing to be solid, then vacuumizing, freezing and drying to be spongy to obtain an anti-adhesion layer B, and spraying the second solution group onto two surfaces or one surface of the anti-adhesion layer B by using a spraying device to obtain an ABA type or AB type absorbable anti-adhesion material;

type BAB: pouring the second solution group into a mold, freezing and coagulating to a solid state, then vacuumizing, and freezing and drying to a spongy state to obtain an antibacterial and anti-inflammatory layer A; and (3) spraying the first solution group on two sides of the antibacterial and anti-inflammatory layer A by using a spraying device to obtain the BAB type absorbable anti-adhesion material.

In the above production method, as a preferred embodiment, the water in step (a) is water for injection or sterilized water for injection.

In the above preparation method, as a preferred embodiment, the water content of the first solution set in step (a) is 40 wt% to 90 wt% (e.g., 50 wt%, 60 wt%, 70 wt%, 80 wt%), preferably 52 wt% to 88.89 wt% (e.g., 55 wt%, 58 wt%, 62.5 wt%, 67.5 wt%, 72.5 wt%, 77.5 wt%, 82.5 wt%, 85 wt%).

In the above-mentioned preparation method, as a preferred embodiment, the water content of the second solution group in the step (b) is 32 wt% to 88 wt% (e.g., 35 wt%, 40 wt%, 50 wt%, 60 wt%, 70 wt%, 80 wt%).

In the above-mentioned production method, as a preferred embodiment, the water content of the absorbable anti-blocking material produced in step (c) is 10% or less (e.g., 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%).

The invention adopts the water for injection as the solvent, on one hand, the harm of the organic solvent to human bodies is avoided, on the other hand, the water with the corresponding grade can be selected according to the difference of wound positions, and when the anti-adhesion material is used in vivo, the water for injection or the sterilized water for injection is selected.

In the above preparation method, as a preferred embodiment, the method further comprises: (d) freezing and condensing the absorbable anti-adhesion material obtained in the step (c) to be solid, then vacuumizing and freeze-drying to be spongy, cutting into different shapes according to different wound positions and wound shapes, packaging in a package, and sealing.

In the above preparation method, as a preferred embodiment, the method further comprises: step (e), sterilizing the sealed absorbable anti-adhesion material obtained in step (d); preferably, the sterilization is one of ethylene oxide sterilization, gamma ray sterilization, electron beam sterilization, dry heat sterilization, and ozone sterilization.

In the above production method, as a preferable embodiment, the stirring speed is 50 to 500rpm/min (e.g., 100rpm/min, 150rpm/min, 200rpm/min, 250rpm/min, 300rpm/min, 350rpm/min, 400rpm/min, 450 rpm/min).

In the above production method, as a preferred embodiment, the temperature of the freezing is-10 ℃ to-100 ℃ (e.g., -20 ℃, -30 ℃, -40 ℃, -50 ℃, -60 ℃, -70 ℃, -80 ℃, -90 ℃); preferably, the degree of vacuum is-0.05 MPa to-0.1 MPa (e.g., -0.06MPa, -0.07MPa, -0.08MPa, -0.09 MPa).

The freezing temperature used in the present invention is preferably below-10 ℃, and too high freezing temperature or too short freezing time can cause bubbling of the product during freeze drying, which affects the final product form of the product.

In the above production method, as a preferred embodiment, the plasticizer is a polyhydric alcohol; preferably, the polyol is glycerol and/or polyethylene glycol.

In the above preparation method, as a preferred embodiment, when the absorbable anti-blocking material has a multilayer structure form of AB type, the mass ratio of the antibacterial and anti-inflammatory layer a to the anti-blocking layer B is 1: (0.01-100) (e.g., 1:1, 1:10, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90), preferably 1: (0.02-50) (e.g., 1:0.05, 1:0.1, 1:0.5, 1:1.5, 1:3, 1:6, 1:9, 1:15, 1:25, 1:35, 1: 45).

In the above production method, as a preferred embodiment, when the absorbable anti-blocking material has an ABA type multilayer structure, the mass ratio of the total mass of the antibacterial and anti-inflammatory layer a to the anti-blocking layer B is 1: (0.01-100) (e.g., 1:1, 1:10, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90), preferably 1: (0.02-50) (e.g., 1:0.05, 1:0.1, 1:0.5, 1:1.5, 1:3, 1:6, 1:9, 1:15, 1:25, 1:35, 1: 45).

The bioactive mineral material used in the invention has repairing and bonding effects on soft tissues and bone tissues, and has good biocompatibility and osteoconductivity; the bioactive mineral material has effects of promoting fibroblast proliferation and collagen matrix regeneration, and its retention time in vivo can be adjusted by high temperature sintering, so as to solve the problem of short injection period of other materials (such as hyaluronic acid).

Compared with the prior art, the invention has the advantages that:

(1) the absorbable anti-adhesion material is prepared by compounding the bioactive mineral material through the specific properties of the bioactive mineral material and the retention time of the bioactive mineral material in a living body. The bioactive mineral material forms a three-dimensional network structure after contacting with body fluid, is beneficial to the proliferation and climbing of cells, guides the differentiation of cells, enables tissues to be tightly combined, accelerates the healing of wounds, and effectively prevents the adhesion of tissues after the wound surface is repaired.

(2) The degradable anti-adhesion material prepared by the invention has controllable degradation period, the degradation time of the product in the human body is adjusted through the type and molecular weight of the degradable and absorbable high molecular material of the human body and the sintering temperature of the bioactive mineral material, and the degradation time is adjusted according to the requirements of different wound parts.

In addition, the anti-adhesion material of the invention is gradually degraded into low molecular weight compounds or monomers in vivo through hydrolysis, enzymolysis and other processes, and the degradation products can be discharged out of the body or can participate in normal metabolism in the body to disappear; avoiding secondary taking-out operation, reducing the pain of the patient and simultaneously avoiding forming foreign matters existing in the human body for a long time.

(3) The invention explores the important value of the trace elements on human structures and organs, adds more than 20 trace elements which are beneficial to human tissues into the anti-adhesion material, promotes the metabolism of tissue cells, enhances the cell activity, improves the immunity, resists the invasion of bacteria and viruses, and prevents and treats various inflammations.

(4) The absorbable anti-adhesion material prepared by the invention is of a porous structure (gaps formed by sublimation in the vacuum freeze drying process and a porous structure possessed by a bioactive mineral material), has a large specific surface area, forms a three-dimensional network structure after contacting with body fluid, is beneficial to proliferation and climbing of cells, guides cell differentiation, enables tissues to be tightly combined, accelerates wound healing, and effectively prevents tissue adhesion after wound repair.

(5) The absorbable anti-adhesion material prepared by the invention integrates the advantages of antibiosis, anti-inflammation, wound healing acceleration, controllable degradation, safety, no stimulation and the like, and provides an anti-adhesion material integrating multifunctionality and convenience for patients.

(6) The absorbable anti-adhesion material prepared by the invention is suitable for in-vivo and in-vitro wound surfaces, such as liver/lung injuries, uterine cavity adhesion, heart operation injuries, caesarean section operation injuries and in-vitro acute and chronic wound surfaces, can accelerate wound healing, and can adjust the degradation period of the anti-adhesion material according to different wound surface parts.

(7) The absorbable anti-adhesion material prepared by the invention is composed of a high polymer material which can be degraded and absorbed by a human body, and the solvent is water, so that the harm caused by using an organic solvent is avoided.

(8) The anti-adhesion material in a single-layer or multi-layer structure form is adopted, so that the anti-adhesion material is suitable for different wound parts; and according to the shape of the wound, a round, rectangular, heart-shaped, polygonal and three-dimensional structure which is suitable for the wound can be made.

(9) The absorbable anti-adhesion material prepared by the invention is soft in texture, has certain tensile strength, is more beneficial to tight combination of tissues, and can improve the comfort of patients.

Drawings

FIG. 1 is an EDX spectrum of bioactive glass, wherein the content of calcium ions in the bioactive glass is 23.5 wt%;

FIG. 2 is an EDX spectrum of Regesi regenerated silicon, wherein the Regesi regenerated silicon has a calcium ion content of 34.3 wt%.

Detailed Description

To better illustrate the objects, technical solutions and advantages of the present invention, the absorbable anti-adhesion material prepared by the present invention with antibacterial, anti-inflammatory, wound healing accelerating and degradation period controlling functions will be further described with reference to the following specific examples and comparative examples, but the present invention is not limited by these specific examples and comparative examples.

The bioactive glass used in the embodiment of the invention is 45S5 of Schottky/Nopont, the EDX energy spectrum of the bioactive glass is shown in figure 1, and the content of calcium ions in the bioactive glass is 23.5 wt%; the Regesi regenerated silicon used in the embodiment of the invention is as follows according to the application publication number: CN111017934A, the method of Chinese patent. The RegeSi regenerated silicon comprises: the calcium phosphate/calcium silicate composite material comprises a bracket which is formed by stacking nano-scale silicon dioxide particles and has a porous structure, and calcium and phosphorus elements which are uniformly distributed in the bracket, wherein the calcium phosphate/calcium silicate composite material is a calcium phosphate/calcium silicate compound with biological activity; the specific surface area of the regenerated silicon is 200-350 square meters per gram; the corresponding commercial product is regenerated silicon produced by Happy probiotic regenerative medicine science and technology Limited, the EDX energy spectrum of the regenerated silicon is shown in figure 2, and the calcium ion content in the Regesi regenerated silicon is 34.3 wt%.

Example 1

Take the preparation of sodium hyaluronate-bioactive glass-glycerin-beta lactam-trace element stock solution anti-adhesion material as an example.

Dissolving 1 g of sodium hyaluronate in 87.89 g of water for injection, heating to 60-80 ℃, stirring and dissolving to obtain a sodium hyaluronate aqueous solution, adding 0.1 g of glycerol, 0.01 g of bioactive glass and 10 g of trace element stock solution, uniformly stirring, dividing into two groups, wherein one group has the mass of 10 g, adding 1 g of beta lactam anti-inflammatory component, uniformly stirring to obtain a second solution group for preparing an antibacterial anti-inflammatory layer, and standing for later use; and the other solution group with the mass of 89 g is the first solution group for preparing the anti-adhesion layer, is injected into a mold and then is placed into a freezing box, the temperature is-10 ℃, the other solution group is taken out after being frozen for 24 hours and then is placed into a vacuum freeze dryer, and the other solution group is taken out after being vacuum-dried for 20 hours, so that the anti-adhesion layer B is obtained. And spraying the second solution group for preparing the antibacterial and anti-inflammatory layer on the front side and the back side of the anti-adhesion layer B, putting the anti-adhesion layer B into a vacuum freeze dryer after spraying, drying for 5 hours, taking out, repeatedly spraying and drying for 3 cycles, and completely spraying the second solution group for preparing the antibacterial and anti-inflammatory layer on the surface of the anti-adhesion layer B to obtain the absorbable anti-adhesion material (hyaluronic acid sodium-bioactive glass-glycerol-beta lactam-trace element stock solution) with antibacterial, anti-inflammatory, wound healing acceleration and controllable degradation.

Example 2

Take the preparation of sodium hyaluronate/sodium carboxymethylcellulose-Regesi regenerated silica-glycerin-beta lactam-microelement stock solution anti-adhesion material as an example.

Dissolving 1 g of sodium hyaluronate and 1 g of sodium carboxymethylcellulose in 72 g of water for injection, heating to 60-80 ℃, stirring and dissolving to obtain a sodium hyaluronate/sodium carboxymethylcellulose aqueous solution, adding 6 g of glycerol, 5 g of Regesi regenerated silicon and 10 g of trace element stock solution, uniformly stirring, dividing into two groups, wherein one group has the mass of 20 g, adding 5 g of beta lactam anti-inflammatory component, uniformly stirring to obtain a second solution group for preparing an antibacterial and anti-inflammatory layer, and standing for later use; the other group, which was 75 g in mass, was the first solution group used to prepare the anti-blocking layer, which was injected into a mold and placed in a freezer at-20 ℃ for 10 hours, after freezing, taken out, placed in a vacuum freeze-dryer, and after vacuum drying for 20 hours, taken out to obtain the anti-blocking layer B. And spraying the second solution group for preparing the antibacterial and anti-inflammatory layer on the front side and the back side of the anti-adhesion layer B, putting the anti-adhesion layer B into a vacuum freeze dryer after spraying, drying for 5 hours, taking out, repeatedly spraying and drying for 3 cycles, and completely spraying the second solution group for preparing the antibacterial and anti-inflammatory layer on the surface of the anti-adhesion layer B to obtain the absorbable anti-adhesion material (sodium hyaluronate/sodium carboxymethylcellulose-Regesi regenerated silicon-glycerol-beta lactam-microelement stock solution anti-adhesion material) with antibacterial and anti-inflammatory effects, wound healing acceleration and controllable degradation.

Example 3

The preparation of the sodium carboxymethylcellulose-Regesi regenerated silicon-polyethylene glycol-beta lactam-microelement stock solution anti-adhesion material is taken as an example.

Dissolving 2 g of sodium carboxymethylcellulose in 75.98 g of water for injection, heating to 60-80 ℃, stirring and dissolving to obtain a sodium carboxymethylcellulose aqueous solution, adding 10 g of polyethylene glycol, 10 g of Regesi regenerated silicon and 2 g of trace element stock solution, uniformly stirring, dividing into two groups, wherein one group has the mass of 1 g, adding 0.02 g of beta-lactam anti-inflammatory component, uniformly stirring to obtain a second solution group for preparing an antibacterial and anti-inflammatory layer, and standing for later use; and the other group is 98.98 g, is a first solution group for preparing the anti-adhesion layer, is injected into a mold and then is placed into a freezing box at the temperature of minus 50 ℃, is frozen for 4 hours and then is taken out, is placed into a vacuum freeze dryer and is taken out after being vacuum-dried for 20 hours, and the anti-adhesion layer B is obtained. And spraying the second solution group for preparing the antibacterial and anti-inflammatory layer on the front and back surfaces of the anti-adhesion layer B, putting the anti-adhesion layer B into a vacuum freeze dryer after spraying, drying for 5 hours, taking out, repeatedly spraying and drying for 3 cycles, and spraying all the second solution group for preparing the antibacterial and anti-inflammatory layer on the surface of the anti-adhesion layer B to obtain the absorbable anti-adhesion material (sodium carboxymethyl cellulose-Regesi regenerated silicon-polyethylene glycol-beta lactam-trace element stock solution anti-adhesion material) with the effects of resisting bacteria and diminishing inflammation, accelerating wound healing and controlling degradation.

Example 4

The anti-adhesion material of chitosan/sodium hyaluronate-Regesi regenerated silicon-polyethylene glycol-beta lactam-microelement stock solution is prepared as an example.

Dissolving 1 g of chitosan and 1 g of sodium hyaluronate in 75.98 g of water for injection, heating to 60-80 ℃, stirring and dissolving to obtain a chitosan/sodium hyaluronate aqueous solution, adding 10 g of polyethylene glycol, 10 g of Regesi regenerated silicon and 2 g of trace element stock solution, uniformly stirring, dividing into two groups, wherein one group has the mass of 1 g, adding 0.02 g of beta lactam anti-inflammatory component, uniformly stirring to obtain a second solution group for preparing an antibacterial and anti-inflammatory layer, and standing for later use; the other group, which was 98.98 g in mass, was the first solution group for the preparation of the anti-blocking layer, which was injected into a mold and placed in a freezer at-50 ℃ for 4 hours, after freezing, taken out, placed in a vacuum freeze-dryer, and after vacuum drying for 20 hours, taken out to obtain the anti-blocking layer B. And spraying the second solution group for preparing the antibacterial and anti-inflammatory layer on the front side and the back side of the anti-adhesion layer B, putting the anti-adhesion layer B into a vacuum freeze dryer after spraying, drying for 5 hours, taking out, repeatedly spraying and drying for 3 cycles, and completely spraying the second solution group for preparing the antibacterial and anti-inflammatory layer on the surface of the anti-adhesion layer B to obtain the absorbable anti-adhesion material (chitosan/sodium hyaluronate-Regesi regenerated silicon-polyethylene glycol-beta lactam-trace element stock solution anti-adhesion material) with antibacterial and anti-inflammatory effects, wound healing acceleration and controllable degradation.

Example 5

Take the preparation of chitosan/sodium hyaluronate-hydroxyapatite-polyethylene glycol-coptis extract-microelement stock solution anti-adhesion material as an example.

Dissolving 1 g of chitosan and 1 g of sodium hyaluronate in 36 g of water for injection, heating to 60-80 ℃, stirring and dissolving to obtain a chitosan/sodium hyaluronate aqueous solution, adding 20 g of polyethylene glycol, 20 g of hydroxyapatite and 6 g of trace element stock solution, uniformly stirring, dividing into two groups, wherein one group has the mass of 50 g, adding 16 g of coptis extract, uniformly stirring to obtain a second solution group for preparing an antibacterial and anti-inflammatory layer, and standing for later use; the other group, 34 g, was the first solution group for the preparation of the anti-blocking layer, which was injected into a mold and placed in a freezer at a temperature of-80 ℃ for 3 hours, after freezing, taken out, placed in a vacuum freeze-dryer, after vacuum drying for 20 hours, taken out to obtain the anti-blocking layer B. And spraying the second solution group for preparing the antibacterial and anti-inflammatory layer on the front side and the back side of the anti-adhesion layer B, putting the anti-adhesion layer B into a vacuum freeze dryer after spraying, drying for 5 hours, taking out, repeatedly spraying and drying for 3 cycles, and spraying all the second solution group for preparing the antibacterial and anti-inflammatory layer on the surface of the anti-adhesion layer B to obtain the absorbable anti-adhesion material (chitosan/sodium hyaluronate-hydroxyapatite-polyethylene glycol-coptis chinensis extract-trace element stock solution anti-adhesion material) with antibacterial and anti-inflammatory effects, wound healing acceleration and controllable degradation.

Example 6

Take the preparation of starch/chitosan-bioactive glass (45S 5 from Schottky/Nobang) -glycerin-aminopolysaccharide quaternary ammonium salt-microelement stock solution anti-adhesion material as an example.

Dissolving 1 g of starch and 2 g of chitosan in 60 g of water for injection, heating to 60-80 ℃, stirring and dissolving to obtain a starch/chitosan aqueous solution, adding 12 g of glycerol, 15 g of bioactive glass and 2 g of trace element stock solution, uniformly stirring, dividing into two groups, wherein one group has the mass of 20 g, adding 9 g of amino polysaccharide quaternary ammonium salt, uniformly stirring to obtain a second solution group for preparing an antibacterial and anti-inflammatory layer, and standing for later use; the other group, which was 71 g in mass, was the first solution group for the preparation of the anti-blocking layer, which was placed in a freezer at-100 ℃ after being injected into a mold, frozen for 2 hours, taken out, placed in a vacuum freeze-dryer, and taken out after vacuum drying for 20 hours, to obtain the anti-blocking layer B. And spraying the second solution group for preparing the antibacterial and anti-inflammatory layer on the front side and the back side of the anti-adhesion layer B, putting the anti-adhesion layer B into a vacuum freeze dryer after spraying, drying for 5 hours, taking out, repeatedly spraying and drying for 3 cycles, and spraying the second solution group for preparing the antibacterial and anti-inflammatory layer on the surface of the anti-adhesion layer B to obtain the absorbable anti-adhesion material (the starch/chitosan-bioactive glass-glycerol-amino polysaccharide quaternary ammonium salt-trace element stock solution anti-adhesion material) with antibacterial and anti-inflammatory effects, wound healing acceleration and controllable degradation.

Example 7

The preparation of starch/chitosan-bioactive glass (schottky/noconb 45S5) -glycerin-aminopolysaccharide quaternary ammonium salt anti-adhesion material is taken as an example.

Dissolving 1 g of starch and 2 g of chitosan in 62 g of water for injection, heating to 60-80 ℃, stirring and dissolving to obtain a starch/chitosan aqueous solution, adding 12 g of glycerol and 15 g of bioactive glass, uniformly stirring, dividing into two groups, adding 9 g of aminopolysaccharide quaternary ammonium salt into one group, uniformly stirring to obtain a second solution group for preparing an antibacterial and anti-inflammatory layer, and standing for later use; the other group with the mass of 71 g is used for preparing the first solution group of the anti-adhesion layer, the first solution group is poured into a mold and then is placed into a freezing box at the temperature of-100 ℃, and the second solution group is taken out after being frozen for 2 hours and then is placed into a vacuum freeze dryer, and is taken out after being vacuum dried for 20 hours, so that the anti-adhesion layer B is obtained. And spraying the second solution group for preparing the antibacterial and anti-inflammatory layer on the front and back surfaces of the anti-adhesion layer B, putting the anti-adhesion layer B into a vacuum freeze dryer after spraying, drying for 5 hours, taking out, repeatedly spraying and drying for 3 cycles, and spraying the second solution group for preparing the antibacterial and anti-inflammatory layer on the surface of the anti-adhesion layer B to obtain the absorbable anti-adhesion material (the starch/chitosan-bioactive glass-glycerol-aminopolysaccharide quaternary ammonium salt anti-adhesion material) with the functions of antibiosis, anti-inflammation, wound healing acceleration and controllable degradation.

Comparative example 1

Take the preparation of sodium hyaluronate-glycerin-microelement stock solution anti-adhesion material as an example.

Dissolving 1 g of sodium hyaluronate in 88.9 g of water for injection, heating to 60-80 ℃, stirring to dissolve to obtain a sodium hyaluronate aqueous solution, adding 0.1 g of glycerol and 10 g of trace element stock solution, uniformly stirring, injecting the sodium hyaluronate aqueous solution into a mold, putting the mold into a freezing box, freezing for 24 hours, taking out, putting the mold into a vacuum freeze dryer, and vacuum drying for 20 hours, and taking out to obtain the absorbable anti-adhesion material (sodium hyaluronate-glycerol-trace element stock solution).

Comparative example 2

Take the preparation of sodium hyaluronate/sodium carboxymethylcellulose-glycerin-beta lactam-microelement stock solution anti-adhesion material as an example.

Dissolving 1 g of sodium hyaluronate and 1 g of sodium carboxymethylcellulose in 77 g of water for injection, heating to 60-80 ℃, stirring and dissolving to obtain a sodium hyaluronate/sodium carboxymethylcellulose aqueous solution, adding 6 g of glycerol and 10 g of trace element stock solution, uniformly stirring, dividing into two groups (group 1 and group 2), wherein the mass of the group 1 is 75 g, the group 1 is used for preparing an anti-adhesion layer, injecting the anti-adhesion layer into a mold, then placing the mold into a freezing box, freezing at-20 ℃, taking out after 10 hours, placing the mold into a vacuum freeze dryer, and taking out after 20 hours of vacuum drying to obtain an anti-adhesion layer B; the mass of the group 2 is 20 g, the group is used for preparing an antibacterial and anti-inflammatory layer, 5 g of beta lactam anti-inflammatory component is added, and the mixture is uniformly stirred to obtain an antibacterial and anti-inflammatory solution group 3 which is kept stand for later use. And (3) spraying the antibacterial and anti-inflammatory solution group 3 on the front and back surfaces of the anti-adhesion layer B, putting the anti-adhesion layer B into a vacuum freeze dryer after spraying, drying for 5 hours, taking out, repeatedly spraying and drying for 3 cycles, and completely spraying the antibacterial and anti-inflammatory solution group 3 on the surface of the anti-adhesion layer B to obtain the absorbable anti-adhesion material (sodium hyaluronate/sodium carboxymethylcellulose-glycerol-beta lactam-microelement stock solution anti-adhesion material).

The basic performance evaluation of the absorbable anti-adhesion material prepared in examples 1 to 7, which has the effects of resisting bacteria, diminishing inflammation, accelerating wound healing and controlling degradation, and the absorbable anti-adhesion material prepared in comparative examples 1 to 2 specifically includes the following contents:

(1) water absorption rate

Each of the anti-blocking materials of comparative examples 1 to 2 and examples 1 to 7 was cut into pieces of 3cm by 3cm, weighed to obtain M1, placed in a sterile simulated body fluid at 37 ℃ and weighed to obtain M2 after 12 hours, and then the water absorption was calculated. The water absorption rate is (M2-M1)/M1, and the test result of the water absorption rate is as follows:

from the above results, it is understood that the water absorption rate is highest in example 2 and lowest in examples 6 and 7.

(2) Mechanical properties

Each anti-adhesion material in comparative examples 1-2 and examples 1-7 was cut into 3cm by 3cm, a mechanical property test of the anti-adhesion material was performed using a universal testing machine, and the tensile strength test results were as follows:

from the above results, it is understood that the mechanical properties of comparative example 2 and example 2 are the best, and the mechanical properties of example 5 are the worst, probably due to the excessive addition of powders such as bioactive mineral materials and herbal extracts.

(3) Hemostatic properties

SPF grade SD rats were prepared in 30 groups of 3 animals at random. Using SD rats with bleeding due to liver injury as a model, rats were anesthetized and abdominal hair was shaved, and the abdomen was opened with a scalpel to expose the liver. A wound with a length of 1cm and a depth of 1cm was made on the liver with a scalpel. The samples prepared in comparative examples 1-2 and examples 1-7 were covered on the top of a bleeding liver, covered with a gauze pad, and subjected to a conventional pressing operation. The gauze is lifted every 5s, the bleeding condition is observed until hemostasis is realized, and the bleeding time and the bleeding amount are counted.

The adhesion-preventing materials prepared in comparative examples 1 to 2 and examples 1 to 7 and a control group (gauze) were used for the following liver hemostasis test, respectively. The test results are reported below:

from the above results, it is understood that the anti-adhesion materials prepared in comparative examples 1 to 2 and examples 1 to 7 have a certain hemostatic effect as compared with the control group, and the hemostatic effects of the anti-adhesion materials prepared in comparative example 1 and examples 1 to 7 are in the order of superiority and inferiority: example 4> example 3> example 2> example 6> example 7> example 5> comparative example 2> example 1> comparative example 1> control. Among them, the anti-blocking materials prepared in examples 4 and 3 had the best hemostatic effect, probably because Regesi regenerated silicon was added in the formulations of examples 4 and 3 in a higher amount. The hemostatic effect of the regenerated silicon containing 5% of Regesi in example 2 is not much different from that of the regenerated glass containing 15% of bioactive glass in example 6, which is probably caused by the fact that the content of calcium ions in the Regesi regenerated silicon is higher than that of the bioactive glass, and due to the introduction of a proper amount of calcium ions, the degradation rate of the finally prepared anti-adhesion material can be controlled, the necessary calcium ions can be provided for blood coagulation, and the calcium ions and the anti-adhesion material generate a synergistic effect to accelerate the hemostasis speed.

(4) Surface adhesion

SPF grade SD rats were prepared in 27 groups of 3 animals at random. The back skin of SD rat is cut into a wound surface with 1cm x 1cm, then the anti-adhesion material samples in comparative examples 1-2 and examples 1-7 are attached to the wound surface area, after being pressed for 10min, the anti-adhesion material samples are peeled from the side surfaces of the material, the measured pulling force value is the surface adhesion strength of the wound surface, and each sample is tested for 3 times and the average value is taken. The measured surface adhesion results are as follows:

from the above results, it is understood that the surface adhesion of the anti-blocking materials prepared in comparative examples 1 to 2 and examples 1 to 7 is in the order of: comparative example 2> example 1> example 4> comparative example 1> example 4> example 5> example 6 ═ example 7. The adhesion-preventing material prepared in the comparative example 2 has the largest adhesion force, and the possible reason is that the adhesion force of the human degradable and absorbable polymer material adopted in the formula is stronger; the adhesion was minimal for examples 6 and 7, probably because the synergy of the bioactive glass in the formulation with the starch/chitosan reduced the surface adhesion of the material.

(5) In vitro degradation

Each sample of the anti-adhesion material prepared in comparative examples 1-2 and examples 1-7 was cut into 2cm × 2cm, weighed to obtain a0, and then the anti-adhesion material was put into 20ml of human body simulated body fluid, and put in a constant temperature shaking table at 37 ℃ for simulated degradation, the simulated body fluid was changed every day, and the change of the sample in the simulated body fluid was observed. After 72 hours, the anti-blocking material was taken out, dried and weighed to obtain An.

The degradation rate (degradation rate ═ a0-An)/a0) was calculated and the test results were recorded as follows:

from the above results, it can be seen that the samples prepared in comparative examples 1 to 2 and examples 1 to 7 had degradation rates ranging from large to small in the in vitro degradation test in the following order: comparative example 1> comparative example 2> example 1> example 2> example 3> example 4> example 5> example 6-example 7, the addition of bioactive mineral material greatly reduced the degradation rate of the anti-blocking material of the present invention.

(6) Biocompatibility

Test groups: 108 SD rats were selected, the anti-adhesion materials prepared in comparative examples 1 to 2 and examples 1 to 7 were placed in subcutaneous tissues on the backs of rats, sacrificed (3/time) in 3 days, 7 days, 14 days, and 21 days, respectively, local reactions were observed, the materials and surrounding tissues were taken out, HE stained sections were observed, and inflammatory reactions around the tissues of the anti-adhesion materials were further observed to evaluate the biocompatibility of the anti-adhesion materials.

Control group: 12 SD rats were selected, the dorsal wound was directly closed with surgical sutures, sacrificed (3/time) on 3 days, 7 days, 14 days, 21 days and observed for local reactions.

Criteria for wound healing: the wound healing area is greater than 95% of the original wound area or the wound area is less than 5% of the original wound area, i.e. complete healing.

And (3) test results: SD rats in the test group and the control group completely survive, wounds completely heal, and tissues at the positions where the anti-adhesion materials are placed have no suppuration, edema, hyperemia and necrosis, which shows that the anti-adhesion materials prepared in the comparative examples 1-2 and the examples 1-7 are harmless to the rats and have good biocompatibility.

(7) Bacteriostasis test

The test bacteria are selected from Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger. Preparing the prepared anti-adhesion material and water according to the mass ratio of 1:20 to obtain a test sample, taking 4 parts of the test sample (5 ml/sample), and directly inoculating test bacteria; 1ml of the sample was transferred to 4 sterile containers, each of which was inoculated with one of the test bacteria (inoculum 10) ⁸ 0.05ml bacterial liquid of cfu/ml), 1ml test sample is inoculatedThe bacterial count is 10 ⁵ ～10 ⁶ cfu, the volume of the inoculated bacteria liquid is not more than 1 percent of the volume of the test sample, and the inoculated bacteria liquid and the test sample are fully mixed to ensure that the test bacteria in the test sample are uniformly distributed. Inoculating staphylococcus aureus and pseudomonas aeruginosa in trypticase soy peptone agar culture medium at the culture temperature of 30-35 ℃ for 18-24 hours; inoculating Candida albicans in a glucose agar culture medium of Saccharum sinensis Roxb, and culturing at 20-25 deg.C for 2-3 days; inoculating Aspergillus niger in a Sabouraud's glucose agar culture medium, and culturing at 20-25 deg.C for 5-7 days.

The anti-adhesion materials prepared in comparative examples 1-2 and examples 1-7 were selected as test samples, and the control group was a blank of the culture medium.

The test results show that the anti-adhesion materials prepared in the comparative examples 1-2 have the phenomenon of inhibiting the growth of bacterial colonies, and the trace element stock solution has the effects of sterilization and inflammation diminishing; the samples of examples 1-7 all had good inhibition of colony growth, with the best inhibition of example 2 (minimal number of colonies in the medium).

(8) Anti-adhesion effect test

Test groups: SD rats were selected at 27 and randomly divided into 9 groups of 3 rats each. After one week of acclimatization, an intestinal adhesion wound model was prepared on the small intestine of rats, the anterior serosal surface of the cecum was gently scraped with a surgical brush to cause slight bleeding, the test material (the adhesion-preventing material prepared in comparative examples 1-2 and examples 1-7) was directly wrapped on the wound surface, and the adhesion condition and histological morphology of the wound surface were observed after 3 weeks.

Control group: selecting 3 SD rats, adaptively feeding for one week, making an intestinal adhesion wound surface model on the small intestine of the rat, lightly scraping the serosal surface of the cecum by using an operation brush to cause slight blood leakage, directly suturing the wound without treatment, and observing the adhesion condition and the histological morphology of the wound surface after 3 weeks.

The experimental results are as follows: the surface of the rat wound of the control group and the surrounding mesentery are adhered in a large area, are difficult to separate and belong to III-grade adhesion; the experimental group shows that the anti-adhesion material in the proportion 1-2 slightly adheres between the acting part and the surrounding mesentery; experimental group the adhesion-preventing materials of examples 1 to 7 did not adhere to the abdominal wall and the surrounding mesentery at the site of action, and a part of the test material remained on the wound surface.

It can be seen that the materials of examples 1-7 adhere well to wounds and inhibit the occurrence of post-operative adhesions.

(9) Wound healing efficacy test

30 SPF-grade SD rats were prepared and, after one week of acclimatization, were randomly divided into 10 groups, including a test group and a control group, of 3 rats each. After anaesthetizing, the rat is cut off hair on the back, the skin is disinfected, a full-layer skin wound model with the diameter of 1.6cm is respectively established at the same position of two sides of the spine, and the rat is bred in a single cage after model building. Taking a sterile ruler to measure the diameter of the wound every 2 days, taking a picture to record and observe the healing condition of the wound, and calculating the wound healing rate within 14 days.

The experimental group used the anti-adhesion materials prepared in comparative examples 1-2 and examples 1-7 to treat the skin wound of rats;

the control group was exposed to wound and was routinely hemostatic and fluid-exudative cleansed.

The calculation formula of the wound healing rate is as follows: rate of healing ═ (original wound area-non-healed wound area)/original wound area 100%.

The recorded results of the wound healing rate were as follows:

from the above results, it can be seen that the samples prepared in comparative examples 1-2 and examples 1-7 had superior wound healing effects on rat skin to the control group. The samples of comparative examples 1-2 had better healing effect on the skin wounds of rats than the control group, probably because trace elements had healing-promoting effect on the wounds; the good and bad order of the healing effect of the samples of examples 1-7 on the wound skin is: example 3> example 2> example 6> example 7> example 5> example 1, the wound healing effect of which may be related to the type and amount of bioactive mineral material added. According to the results, the healing promoting effect of the anti-adhesion material prepared by using the Regesi regenerated silicon as the bioactive mineral material on the wound surface of the rat is better than that of the bioactive glass and the hydroxyapatite.

Claims

1. An absorbable adhesion-prevention material, comprising:

the active ingredients of the antibacterial and anti-inflammatory layer A comprise degradable and absorbable high polymer materials of a human body, a plasticizer, bioactive mineral materials, antibacterial and anti-inflammatory ingredients and trace element stock solution;

and/or the anti-adhesion layer B, wherein the active ingredients of the anti-adhesion layer B comprise degradable and absorbable high polymer materials of human bodies, plasticizers, bioactive mineral materials and trace element stock solution.

2. The absorbable anti-adhesion material according to claim 1, wherein the mass ratio of the active ingredients of the antibacterial and anti-inflammatory layer A is that the active ingredients of the human body degradable and absorbable high molecular material: plasticizer: bioactive mineral material: antibacterial and anti-inflammatory components: the microelement stock solution is 1: (0.1-10): (0.01-10): (0.9-15): (0-10); the anti-adhesion layer B comprises the following active components in percentage by mass: plasticizer: bioactive mineral material: 1: (0.1-10): (0.01-10): (0-10).

3. An absorbable anti-adhesion material according to claim 1, wherein the human degradable and absorbable polymer material comprises: one or more of hyaluronic acid and derivatives thereof, cellulose ether and derivatives thereof, chitosan and derivatives thereof, and starch and derivatives thereof; preferably, the human degradable and absorbable polymer material comprises: one or more of hyaluronic acid, sodium hyaluronate, carboxymethyl cellulose, sodium carboxymethyl cellulose, chitosan and starch.

4. An absorbable anti-adhesion material as claimed in claim 1, wherein the stock solution of trace elements comprises boron, iron, potassium, magnesium, manganese, sodium, phosphorus, titanium, silicon, aluminum, lithium, beryllium, scandium, vanadium, chromium, cobalt, nickel, copper, zinc, gallium, germanium, arsenic, selenium, , strontium, yttrium, zirconium, niobium, molybdenum, silver, cadmium and indium; preferably, the bioactive mineral material refers to an inorganic compound containing silicon, phosphorus and oxygen; preferably, the bioactive mineral material comprises one or more of bioactive glass, Regesi regenerated silicon, hydroxyapatite, phosphosilicate and derivatives thereof, silicate and derivatives thereof, and phosphate and derivatives thereof.

5. The absorbable anti-adhesion material according to claim 1, wherein when the absorbable anti-adhesion material comprises the anti-bacterial and anti-inflammatory layer a and the anti-adhesion layer B, the anti-bacterial and anti-inflammatory layer a is attached to one or both sides of the anti-adhesion layer B; or the anti-adhesion layer B is attached to one side or two sides of the antibacterial and anti-inflammatory layer A; preferably, when the antibacterial and anti-inflammatory layer A is attached to one side or both sides of the anti-adhesion layer B, the mass content of the bioactive mineral material in the antibacterial and anti-inflammatory layer A is lower than that in the anti-adhesion layer B; preferably, the arrangement structure of each layer in the absorbable anti-blocking material is as follows: A. b, AB, ABA or BAB; preferably, the average pore diameter of the antibacterial and anti-inflammatory layer A is 20-500 μm; preferably, the thickness of the antibacterial and anti-inflammatory layer A is 0-10mm, and the tensile strength is 10-300N/cm.

6. The absorbable adhesion-preventing material according to claim 1, wherein the anti-bacterial and anti-inflammatory component of the anti-bacterial and anti-inflammatory layer a comprises: one or more of antibiotic anti-inflammatory component, Chinese medicinal extract and quaternary ammonium salt antibacterial component; preferably, the antibiotic anti-inflammatory component is one or more of beta-lactam antibiotics, aminoglycoside antibiotics, quinolone antibiotics and macrolide antibiotics; preferably, the traditional Chinese medicine extract is one or more of extracts of coptis chinensis, bezoar, scutellaria baicalensis, golden cypress, honeysuckle and fructus forsythiae; preferably, the quaternary ammonium salt antibacterial component is amino polysaccharide quaternary ammonium salt and/or chitosan quaternary ammonium salt.

7. An absorbable adhesion-preventing material according to claim 1, wherein the average pore diameter of the adhesion-preventing layer B is in the range of 20 to 500 μm; preferably, the thickness of the anti-adhesion layer B is 0-10mm, and the tensile strength is 10-300N/cm; preferably, the period of degradation of the absorbable anti-adhesion material in a living body is 3 days to 2 years.

8. The process for preparing an absorbable anti-adhesion material according to any one of claims 1 to 7, comprising the steps of:

(a) according to the dosage proportion of the active ingredients in the anti-adhesion layer B in the absorbable anti-adhesion material, the degradable and absorbable high polymer material is dissolved by water, and then the plasticizer, the bioactive mineral material and the trace element stock solution are added to prepare a first solution group;

(b) according to the dosage proportion of the active ingredients in the antibacterial and anti-inflammatory layer A in the absorbable anti-adhesion material, the degradable and absorbable high polymer material in a human body is dissolved by water, and then the plasticizer, the bioactive mineral material, the trace element stock solution and the antibacterial and anti-inflammatory ingredients are added to prepare a second solution group;

(c) preparing the absorbable anti-adhesion material:

type BAB: pouring the second solution group into a mold, freezing and condensing to be solid, then vacuumizing, and freezing and drying to be spongy, so as to obtain an antibacterial and anti-inflammatory layer A; and (3) spraying the first solution group on two sides of the antibacterial and anti-inflammatory layer A by using a spraying device to obtain the BAB type absorbable anti-adhesion material.

9. The method according to claim 8, wherein the water in step (a) is water for injection or sterilized water for injection; preferably, the water content of the first solution set in step (a) is from 40 wt% to 90 wt%, preferably from 52 wt% to 88.89 wt%; preferably, the water content of the second solution set in step (b) is from 32 wt% to 88 wt%; preferably, the water content of the absorbable anti-blocking material prepared in the step (c) is less than or equal to 10 percent; preferably, the method further comprises: (d) freezing and condensing the absorbable anti-adhesion material obtained in the step (c) to be solid, then vacuumizing and freeze-drying the material to be spongy, cutting the material into different shapes according to different wound parts and wound shapes, packaging the materials in a package, and sealing the package; preferably, the method further comprises: step (e), sterilizing the sealed absorbable anti-adhesion material obtained in the step (d); preferably, the sterilization is one of ethylene oxide sterilization, gamma ray sterilization, electron beam sterilization, dry heat sterilization, and ozone sterilization.

10. The method according to claim 8 or 9, wherein the stirring speed is 50rpm/min to 500 rpm/min; preferably, the freezing temperature is-10 ℃ to-100 ℃; preferably, the vacuum degree is-0.05 MPa to-0.1 MPa; preferably, the plasticizer is a polyol; preferably, the polyol is glycerol and/or polyethylene glycol; preferably, when the absorbable anti-adhesion material is in an AB type multilayer structure, the mass ratio of the antibacterial and anti-inflammatory layer A to the anti-adhesion layer B is 1: (0.01-100), preferably 1: (0.02-50); preferably, when the absorbable anti-adhesion material is in an ABA type multilayer structure, the mass ratio of the total mass of the antibacterial and anti-inflammatory layer A to the anti-adhesion layer B is 1: (0.01-100), preferably 1: (0.02-50).