Degradable material as well as preparation method and application thereof

Abstract

The invention discloses a degradable material as well as a preparation method and application thereof. The degradable material comprises aliphatic polyester and / or modified aliphatic polyester, the degradable material is in a sheet shape, and the thickness of the degradable material is 0.1-8 mm, preferably 2-5 mm. The prepared degradable (face filling and shaping) material is controllable in thickness, can be processed into different shapes according to actual requirements, is soft in texture and light and thin in shape, and reduces displacement and bone resorption caused by gravity; the thickness is only 0.1-8mm, the foreign body sensation is not obvious during filling, the implantation operation is simple and convenient, and the consumed time is short; and the tissue integration is good, the postoperative stability is not easy to displace, bulges and granulation are not formed, and the harm to a human body is avoided.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical devices, in particular to a degradable material and a preparation method and use thereof. BACKGROUND

[0002] With the passage of time, the skin will naturally relax and generate wrinkles, especially facial contour aging will gradually increase, including visible skin wrinkles, deep nasolabial folds, frown lines, puppet wrinkles, cheek junction lines, perioral wrinkles, temporal collapse, etc. Similarly, the collapse of the bridge of the nose and the misalignment of the brow bone and the chin caused by congenital or trauma also bring people distress and suffering. Medical cosmetology facial filling refers to using fillers to fill the face, fill in the concave place, and raise the low place, play the role of modifying the features, filling the contour concave and creating the contour line, and realize the state of full and three-dimensional face. At present, the commonly used facial filling and shaping methods mainly have two kinds, namely, filler implantation and injection method. The injection method has higher requirements for material performance and doctor's injection technique, and the operation price is expensive, and single injection is difficult to maintain for a long time, and needs to be injected again for several months, and is easy to cause postoperative redness and swelling and other phenomena, which gives the operation person a bad feeling, and there is a great safety hazard. Therefore, the filler implantation method still occupies a large market.

[0003] The filling implant is manufactured by making an incision on the skin surface through surgery, implanting the filling material into the subcutaneous space of the facial concave area, and the incision is usually selected on the side of the tragus, and a suitable size space is separated forwardly under the skin. There are three kinds of commonly used filling implant materials, which are hyaluronic acid material, silicone and non-degradable bulking material. Hylauronic acid is widely used in microcosmetic filling field, and is injected into facial tissue as a tissue filler, which can support and fill, so as to achieve the purpose of wrinkle removal. The hyaluronic acid material has strong support and can shape, which can play a role similar to the support of cartilage, and has good effect after operation. Pure and chemically uncrosslinked hyaluronic acid has small tissue reaction and fast degradation rate after being injected into human body, but it cannot maintain the effectiveness of increasing tissue volume for a long time. The crosslinked hyaluronic acid filling material not only has crosslinking agent residues, but also has the risk of being free in the face. Moreover, the face needs to be moved frequently, which causes the hyaluronic acid material to be absorbed quickly, so that the number of additional filling is large, the process is complicated and the price is high. Silicone becomes the most commonly used implant material in rhinoplasty, breast augmentation and other plastic and cosmetic surgeries due to its good biocompatibility, easy plasticity and non-absorption by the body in the later stage, but the implant cannot be fixedly connected with the tissue, and problems such as deformation, displacement and exposure may occur in the later stage. The bulking material is a kind of expanded polymer, and the expanded polytetrafluoroethylene is generally used for facial filling. The expanded polytetrafluoroethylene has fiber voids, and after implantation, the surrounding tissue cells and capillaries can grow into its interior, so that it can be better integrated with the tissue. The expanded polytetrafluoroethylene cannot be degraded in the body, can be fixed in the cheek for a long time, and has little inflammatory cell aggregation around and very light foreign body reaction, and has good effect. However, a large number of postoperative analyses show that because the thickness of most bulking materials is 4-8 mm, the implantation will cause the prosthesis to have a false layer and obvious edge feeling, and the bulking material may also have edge feeling after implantation due to the addition of an adhesive during production, thereby causing local distortion. In addition, since the existing bulking material is non-degradable, it exists permanently in the face and subcutaneous tissue, which may cause facial stiffness and bacterial infection.

[0004] Therefore, it is of great significance to develop a new type of biocompatible, non-rejection, soft-textured and non-pressing surrounding tissue degradable sheet-shaped facial filling implant material for the field of medical and cosmetic surgery. SUMMARY

[0005] In order to solve the problems in the prior art, the present application provides a degradable material and a preparation method and application thereof.

[0006] One of the purposes of the present application is to provide a degradable material, including aliphatic polyester and / or modified aliphatic polyester, which is in the form of a sheet with a thickness of 0.1-8 mm, preferably 2-5 mm. According to the requirements of different parts of the face and different depths, it can be cut into different thicknesses. For example, thinner sheet-like materials are used to fill light to moderate depressions such as skin wrinkles, deep nasolabial folds, marionette lines caused by nasal base depression, frown lines, puppet lines, buccal junction lines, perioral wrinkles, temporal collapse, etc., and thicker sheet-like degradable materials are used to fill severe depressions such as nasal bridge collapse, uneven brow and chin, and congenital or traumatic facial depressions.

[0007] According to the present application, the degradable material is in any sheet-like structure, such as round sheet-like, rectangular sheet-like, oval sheet-like, etc., which can be processed into other different shapes according to actual needs.

[0008] In a preferred embodiment of the present application,

[0009] The degradable material is in one or more of the following sheet-like forms: sheet-like without internal pores, sheet-like with pores having an average pore size of 30-100 microns, preferably sheet-like with pores having an average pore size of 30-100 microns; preferably, the porosity of the sheet-like degradable material with pores having an average pore size of 30-100 microns is 15-85%, preferably 57-80%.

[0010] The sheet-like degradable material with pores having an average pore size of 30-100 microns allows rapid ingrowth of fibrous tissue and capillaries, can be integrated with the tissue, has a low risk of displacement, and autologous immune cells are more easily accessed, greatly reducing the risk of infection.

[0011] In a preferred embodiment of the present application,

[0012] The aliphatic polyester includes one, two or more of polylactic acid, polyglycolic acid, polyhydroxyalkanoate, and polycaprolactone; the number average molecular weight of the aliphatic polyester is preferably 10,000-500,000, more preferably 50,000-200,000; and / or,

[0013] The modified aliphatic polyester is obtained by modifying the aliphatic polyester, and the modification method is at least one of chemical grafting, surface modification, copolymerization, physical blending, and coating. The number average molecular weight of the modified aliphatic polyester is preferably 10,000-500,000, more preferably 50,000-200,000. Both the aliphatic polyester and the modified aliphatic polyester can be obtained from commercial sources or prepared by any method disclosed in the prior art in the field.

[0014] The second object of the present application is to provide a preparation method of the degradable material of the first object of the present application, comprising obtaining the degradable material by at least one of solvent evaporation, foaming-solvent evaporation, melt shaping, melt foaming, electrospinning, 3D printing of components including aliphatic polyester and / or modified aliphatic polyester; preferably, the degradable material is obtained by at least one of foaming-solvent evaporation, melt foaming, electrospinning, 3D printing of components including aliphatic polyester and / or modified aliphatic polyester.

[0015] In a preferred embodiment of the present application,

[0016] The solvent evaporation comprises: dissolving the components including aliphatic polyester and / or modified aliphatic polyester in organic solvent 1, then heating to volatilize the organic solvent 1 (preferably placing the solution in a mold with round sheet-shaped, rectangular sheet-shaped or oval sheet-shaped grooves before volatilization), and finally cooling and solidifying to obtain the degradable material. The sheet-shaped degradable (facial filling shaping) material with different thicknesses can be obtained by controlling the concentration of the components including aliphatic polyester and / or modified aliphatic polyester in the organic solvent 1, and the sheet-shaped degradable material with different thicknesses can also be obtained by cutting. The obtained degradable material has no internal pores and the thickness is 0.1-8mm.

[0017] Preferably, the organic solvent 1 is at least one of dichloromethane, trichloromethane, tetrahydrofuran, ethyl acetate, dimethyl sulfoxide, and more preferably dichloromethane or dimethyl sulfoxide; and / or,

[0018] Preferably, the mass concentration of the solution obtained by dissolving the components including aliphatic polyester and / or modified aliphatic polyester in the organic solvent 1 is 0.1-30%, and more preferably 5-10%; and / or,

[0019] Preferably, the temperature for heating to volatilize the organic solvent 1 is 30-90℃, and / or the temperature for cooling and solidifying is 5-25℃, and the cooling and solidifying time is 2-24h.

[0020] In a preferred embodiment of the present application,

[0021] The foaming-solvent volatilization includes: dissolving components including aliphatic polyester and / or modified aliphatic polyester in organic solvent 2, then adding surfactant and / or foaming agent, stirring and foaming, and then placing in a mold (the mold is a mold with circular sheet-shaped, rectangular sheet-shaped or oval sheet-shaped grooves), and then placing the mold in a vacuum environment, and then heating to volatilize the organic solvent 2, and then cooling and solidifying to form the degradable material. The degradable material obtained by the foaming-solvent volatilization method is a porous sheet-shaped material, the thickness of the obtained porous sheet-shaped material is 0.1-8mm, the average pore size is 30-100 microns, and the porosity is 15-85%, preferably 57-80%.

[0022] In the application, the organic solvent 2 is at least one of dichloromethane, trichloromethane, tetrahydrofuran, ethyl acetate, dimethyl sulfoxide, preferably dichloromethane and / or dimethyl sulfoxide; and / or,

[0023] In the application, the mass concentration of the solution obtained by dissolving the components including aliphatic polyester and / or modified aliphatic polyester in the organic solvent 2 is 0.1-30%, preferably 5-10%; and / or,

[0024] In the application, the surfactant is at least one of anionic surfactant, cationic surfactant, amphoteric surfactant, preferably at least one of triton, span80, silicone oil, sodium dodecyl sulfate, sodium dodecyl benzene sulfonate, more preferably span80 and / or sodium dodecyl sulfate; and / or,

[0025] In the application, the foaming agent is sodium carbonate and / or sodium bicarbonate, preferably 1mol / L aqueous solution of sodium carbonate or sodium bicarbonate; and / or,

[0026] In the application, the mass ratio of the total mass of the surfactant and the foaming agent to the mass of the components including aliphatic polyester and / or modified aliphatic polyester is 0.2-1%; and / or,

[0027] In the application, the temperature for volatilizing the organic solvent 2 is 30-90℃, and / or the cooling and solidification temperature is 5-35℃, preferably 5-25℃, and the cooling and solidification time is 6-24h.

[0028] In a preferred embodiment of the application,

[0029] The melt shaping includes: high-temperature melting of the components including aliphatic polyester and / or modified aliphatic polyester, and then obtaining the degradable material by hot pressing, and the thickness of the obtained sheet-shaped degradable material is 0.1-8mm, and there is no porosity inside; preferably, the components including aliphatic polyester and / or modified aliphatic polyester are vacuum dried before high-temperature melting.

[0030] The high-temperature melting temperature is 150-300℃; and / or,

[0031] The hot-pressing temperature is 120-250℃, the pressure is 5-30MPa, and the time is 1-10min; and / or,

[0032] The vacuum drying temperature is 40-60℃.

[0033] In a preferred embodiment of the present application,

[0034] The melt foaming comprises: hot-pressing the components including the aliphatic polyester and / or modified aliphatic polyester into a sheet shape after melting, and then placing the components in an autoclave to inject supercritical CO2 for foaming reaction to obtain the degradable material; preferably, the components including the aliphatic polyester and / or modified aliphatic polyester are vacuum dried to remove excess moisture before being melted and then placed in the autoclave. The degradable material obtained by the melt foaming method is a foamed sheet material, the obtained foamed sheet material has a thickness of 0.1-8mm, an average pore size of 30-100 microns, and a porosity of 15-85%, preferably 57-80%.

[0035] The melting temperature is 150-300℃; and / or,

[0036] The hot-pressing temperature is 120-250℃, the pressure is 5-30MPa, and the time is 1-10min; and / or,

[0037] The operating conditions of the autoclave include: a temperature of 80-150℃ and a pressure of 5-35MPa; and / or,

[0038] The amount of the supercritical CO2 is 0.01-20% of the mass of the components including the aliphatic polyester and / or modified aliphatic polyester, and / or the foaming reaction time is 0.5-2h; and / or,

[0039] The vacuum drying temperature is 40-60℃.

[0040] In a preferred embodiment of the present application,

[0041] The electrospinning comprises: dissolving the components including the aliphatic polyester and / or modified aliphatic polyester in an organic solvent 3, and then performing electrospinning; a mold having a circular sheet shape, a rectangular sheet shape or an elliptical sheet shape groove is attached to a roller shaft opposite to the nozzle, and the electrospun material is collected layer by layer, dried and solidified to obtain the degradable material. The degradable material obtained by the electrospinning method is a spun sheet material, the obtained spun sheet material has a thickness of 0.1-8mm, an average pore size of 30-100 microns, and a porosity of 15-85%, preferably 57-80%.

[0042] Preferably,

[0043] The electrospinning method comprises the following steps: dissolving components including aliphatic polyester and / or modified aliphatic polyester in an organic solvent 3, stirring and mixing uniformly to prepare a mixed solution for standby; selecting a 4-19 needle for electrospinning; adjusting the distance between the voltage generator and the electrospinning nozzle and the receiving plate, adjusting the flow rate for electrospinning; attaching a mold to the roller shaft opposite the nozzle, layer by layer collecting the spinning, drying and curing to obtain the degradable material.

[0044] Preferably, the organic solvent 3 is at least one of dichloromethane, trichloromethane, tetrahydrofuran, ethyl acetate, dimethyl sulfoxide, preferably dichloromethane or dimethyl sulfoxide; and / or,

[0045] Preferably, the mass concentration of the solution obtained by dissolving components including aliphatic polyester and / or modified aliphatic polyester in the organic solvent 3 is 0.1-30%, preferably 5-10%; and / or,

[0046] Preferably, the distance between the voltage generator and the electrospinning nozzle and the receiving plate is 5-20 cm, preferably 8-12 cm; and / or,

[0047] Preferably, the flow rate of the mixed solution is 0.3-2 mL / h; and / or,

[0048] Preferably, the drying and curing temperature is 30-60℃, and the drying and curing time is 6-24 h.

[0049] In a preferred embodiment of the present application,

[0050] The 3D printing comprises at least one of fused deposition 3D printing and low-temperature 3D printing.

[0051] In a preferred embodiment of the present application,

[0052] The fused deposition 3D printing comprises: placing components including aliphatic polyester and / or modified aliphatic polyester in an extruder for melt extrusion and fiber forming, then obtaining a printing wire after temperature reduction and curing, stretching and traction treatment, and finally obtaining the degradable material after layer-by-layer printing by a 3D printer.

[0053] Preferably,

[0054] The melt deposition 3D printing comprises the following steps: vacuum drying water from components including aliphatic polyester and / or modified aliphatic polyester; placing the dried raw material into a double screw extruder for melt extrusion and wire forming; then obtaining a printing wire after cooling and solidification, stretching and traction treatment; adjusting the printing head of the 3D printer to move parallel to the printing platform, and the wire is brought into the high-temperature printing head by a roller, then extruded after melting, and the molded material is obtained after layer-by-layer printing; the molded material is cooled and solidified, and then vacuum dried to obtain the degradable material.

[0055] Further preferably,

[0056] The preparation process of the melt deposition 3D printing method comprises: vacuum drying water from components including aliphatic polyester and / or modified aliphatic polyester at 40-65°C, and the drying time is 8-48h; placing the dried raw material into a double screw extruder for melt extrusion and wire forming at 60-250°C, and the screw rotation speed is 10-100r / min; then obtaining a printing wire after cooling and solidification, stretching and traction treatment; using a 3D printer comprising an x-y-z movement platform, a computer-aided manufacturing system, an injection controller, a temperature controller (-20-200°C) and a nozzle; adjusting the printing head of the 3D printer to move parallel to the printing platform, and the wire is brought into the high-temperature printing head by a roller, then extruded after melting, and the extrusion speed is 0.5-5.5mm / s, the printing head temperature is 60-250°C, and the printing platform temperature is kept at 50-150°C; obtaining a molded material after layer-by-layer printing, and the material is cooled and solidified at 10-30°C, then vacuum dried at 30-60°C for 6-48h to obtain a 3D printing degradable material; the thickness of the 3D printing degradable material is 0.1-8mm, the average pore size is 30-100 microns, and the porosity is 15-85%, preferably 57-80%. The inner diameter of the printing needle can be selected to be 0.2-0.6mm according to the requirement of material size accuracy in actual application.

[0057] In a preferred embodiment of the present application,

[0058] The low-temperature 3D printing comprises: dissolving components including aliphatic polyester and / or modified aliphatic polyester in an organic solvent 4, placing into a syringe, and obtaining the degradable material by reciprocating layer-by-layer parallel printing through a needle.

[0059] Preferably,

[0060] The low-temperature 3D printing comprises the following steps:

[0061] The components including aliphatic polyester and / or modified aliphatic polyester are dissolved in organic solvent 4 at room temperature to form a mixed solution with a certain concentration; the mixed solution is placed in a syringe, and static defoaming is performed; the temperature is adjusted, and reciprocating layer-by-layer parallel printing is performed through the injection needle at a certain extrusion rate, and the path of each layer is kept consistent; the printed molding material is vacuum dried, and then placed in a room temperature environment for a certain period of time to obtain the degradable material.

[0062] Further preferably,

[0063] The preparation process of the low-temperature extrusion 3D printing method includes: dissolving components including aliphatic polyester and / or modified aliphatic polyester in organic solvent 4 at room temperature to form a solution with a certain concentration; the mixed solution is placed in a syringe, and static defoaming is performed for 0.5-3h; the temperature is adjusted to 20-25℃, and reciprocating layer-by-layer parallel printing is performed through the injection needle at a certain extrusion rate, and the path of each layer is kept consistent; the printed molding material is placed in a vacuum drying oven at 40-60℃ for 24-48h, and then placed in a room temperature environment for 48-72h to obtain a 3D printed degradable material. The 3D printed degradable material has a thickness of 0.1-8mm, an average pore size of 30-100 microns, and a porosity of 15-85%, preferably 57-80%.

[0064] Preferably, the organic solvent 4 is at least one of dichloromethane, trichloromethane, tetrahydrofuran, ethyl acetate, and dimethyl sulfoxide, and more preferably dichloromethane or dimethyl sulfoxide; and / or,

[0065] Preferably, the mass concentration of the solution obtained by dissolving components including aliphatic polyester and / or modified aliphatic polyester in organic solvent 4 at room temperature is 0.1-35%, and more preferably 15-25%; and / or,

[0066] Preferably, the extrusion rate is in the range of 0.5-100mm / s; and / or,

[0067] Preferably, the inner diameter of the injection needle is selected to be 0.2-0.9mm according to the requirement for material size accuracy in actual application.

[0068] The third object of the present application is to provide a use of aliphatic polyester and / or modified aliphatic polyester as a facial filling and shaping material, especially in facial large-size shaping, wherein the aliphatic polyester and / or modified aliphatic polyester is in a sheet-like form with a thickness of 0.1-8mm, and more preferably 2-5mm.

[0069] In a preferred embodiment of the present application,

[0070] The aliphatic polyester and / or modified aliphatic polyester is in one or more of the following sheet-like morphologies: a non-porous sheet-like morphology, a sheet-like morphology containing pores having an average pore size of 30-100 microns, preferably a sheet-like morphology containing pores having an average pore size of 30-100 microns; preferably, the sheet-like morphology containing pores having an average pore size of 30-100 microns has a porosity of 15-85%, preferably 57-80%; and / or,

[0071] The aliphatic polyester includes one or more of polylactic acid, polyglycolic acid, polyhydroxyalkanoate, polycaprolactone; the number average molecular weight of the aliphatic polyester is preferably 10,000-500,000, more preferably 50,000-200,000; and / or,

[0072] The modified aliphatic polyester is obtained by modifying the aliphatic polyester, and the modification method is at least one of chemical grafting, surface modification, copolymerization, physical blending, coating. The number average molecular weight of the modified aliphatic polyester is preferably 10,000-500,000, more preferably 50,000-200,000.

[0073] In one preferred embodiment of the present application,

[0074] The components including the powder or granules of the aliphatic polyester and / or modified aliphatic polyester are used to obtain the sheet-like morphology of the aliphatic polyester and / or modified aliphatic polyester by at least one of solvent evaporation, foaming-solvent evaporation, melt shaping, melt foaming, electrospinning, 3D printing, preferably by at least one of foaming-solvent evaporation, melt foaming, electrospinning, 3D printing.

[0075] The process conditions of the solvent evaporation, foaming-solvent evaporation, melt shaping, melt foaming, electrospinning, 3D printing are as described above.

[0076] In one preferred embodiment of the present application,

[0077] When the aliphatic polyester and / or modified aliphatic polyester is used as a facial filling and shaping material, for facial soft tissue irreversible defects such as skin wrinkles, deep nasolabial folds, frown lines, puppet wrinkles, buccal junction wrinkles, perioral wrinkles, temporal collapse, etc., the sheet-like shaping material is directly filled into the subcutaneous tissue; for nasal bridge collapse, brow bone, chin defect or misalignment, the shape of the defect site or the corrected shape is obtained by MicroCT or other methods, the sheet-like material is obtained by melt shaping method, and then cut into the target size, or the target size sheet-like material is directly obtained by 3D printing, and then the material is directly filled or fixed at the defect site to achieve repair.

[0078] Advantages of the present application:

[0079] The degradable (facial shaping filling) material prepared by the present application can stimulate the in-situ regeneration of collagen after implantation, and the material will gradually degrade and be completely metabolized and absorbed during the collagen regeneration process, with a degradation period of 1-3 years; the degradation products of the material do not harm the facial tissue, and during the degradation process, cells and capillaries can combine with the material and continuously grow into the material, so that the filled part can be regenerated in-situ at a ratio of 1:1.

[0080] The degradable (facial shaping filling) material prepared by the present application has controllable thickness and can be processed into different shapes according to actual needs, with soft texture and light and thin shape, reducing displacement and bone resorption caused by gravity; the thickness is only 0.1-8 mm, and the foreign body sensation is not obvious during filling, the implantation surgery is simple and time-saving; the material has good tissue integration, is stable and not easy to displace after surgery, does not form a bulge and granulation, and does not harm the human body.

[0081] The degradable (facial shaping filling) material prepared by the present application is prepared by an integrated molding process, does not contain organic reagents or toxic chemical components, has excellent biocompatibility, and has no toxic, carcinogenic, and sensitizing side effects; the material has no edge feeling, the edge transition after implantation is natural and plastic, and there is no reflection and light transmission, X-ray does not show, and the effect is natural and real. BRIEF DESCRIPTION OF DRAWINGS

[0082] Figure 1 Collagen content diagram of the degradable (facial filling shaping) material of Example 1 implanted / filled into the subcutaneous tissue of rats in the initial stage (1 month);

[0083] Figure 2 Collagen content diagram of the degradable (facial filling shaping) material of Example 1 implanted / filled into the subcutaneous tissue of rats after 6 months;

[0084] Figure 3 Photo of the degradable (facial filling shaping) material of Example 1 implanted / filled into the subcutaneous tissue of rats in the initial stage (1 month);

[0085] Figure 4 Photo of the degradable (facial filling shaping) material of Example 1 implanted / filled into the subcutaneous tissue of rats after 6 months. DETAILED DESCRIPTION

[0086] The present application will be specifically described below in combination with specific embodiments and drawings, and it is necessary to point out here that the following embodiments are only used to further illustrate the present application, and cannot be understood as limiting the protection scope of the present application, and some non-essential improvements and adjustments of the present application made by those skilled in the art according to the content of the present application still belong to the protection scope of the present application.

[0087] The raw materials used in the examples are all conventional commercially available raw materials.

[0088] Example 1

[0089] 8 g of polylactic acid (number average molecular weight 80000) was dissolved in 92 g of dichloromethane, stirred to completely dissolve, and made into a polylactic acid solution with a mass fraction of 8%, and then dispersed by an ultrasonic cleaner, and left to stand. At 0°C, the solution was placed in a mold with a rectangular thin sheet-shaped groove with a thickness of 1.5 cm, and left to stand to remove bubbles. The mold was placed in a 70°C vacuum drying oven for 6 h to completely volatilize the dichloromethane. Subsequently, the vacuum drying oven was cooled to 10°C and kept for 3 h to solidify the material in the mold. The shaped material was taken out, cut into a thin sheet with a thickness of 3 mm, and a degradable (facial filling and shaping) material finished product was obtained.

[0090] Figures 1-2 The collagen content of the degradable (facial filling and shaping) material of Example 1 implanted / filled into the subcutaneous tissue of rats at the initial stage and after 6 months is shown in the figure; it can be seen that the collagen content is low at the initial stage of implantation / filling, and the collagen content increases significantly (the collagen staining becomes darker) after 6 months, and there is no difference from the original tissue. Figures 3-4 The photos of the degradable (facial filling and shaping) material of Example 1 implanted / filled into the subcutaneous tissue of rats at the initial stage and after 6 months are shown in the figure; it can be seen that at the initial stage of implantation, defects such as stripes and wrinkles exist in the tissue; after 6 months of implantation, the wrinkles disappear, and the filling effect is obvious. Figures 1-4 It can be seen that the material obtained by the present application does not harm the tissue after implantation, and has good compatibility with the tissue; the material can significantly stimulate the regeneration of subcutaneous type III collagen after 3-6 months of implantation; the material can be significantly degraded during in vitro degradation experiments and animal experiments, and after complete degradation of the material, the implanted site regenerates in situ, and the filling effect is obvious.

[0091] Example 2

[0092] Take 5g polycaprolactone (number average molecular weight 100000), add 95g of chloroform, stir well to dissolve completely, prepare a polycaprolactone mass fraction of 5% solution, disperse well with an ultrasonic cleaner, and stand by. Select a 6 static spinning needle, prepare the solution at a voltage of 18kV, a distance of 10cm between the static spinning needle and the receiving plate, and receive at 20℃. Adjust the flow rate of the mixture to 1.5mL / h for spinning. Place the mold with a rectangular flake-shaped groove on the roller opposite the nozzle, and collect the spinning layer by layer. After collecting the spinning, heat to 40℃, dry and solidify for 4h, and shape to obtain a spinning degradable (facial filling and shaping) material finished product. The obtained degradable (facial filling and shaping) material has a thickness of 2mm, and the degradable (facial filling and shaping) material prepared by spinning has a fiber network structure, a fiber diameter of 18 microns, an average pore size of 30 microns, and a porosity of 66%. The average pore size and porosity in the application are determined by nitrogen adsorption method.

[0093] Example 3

[0094] Take 10g polylactic acid-glycolic acid copolymer (number average molecular weight 100000, LA / GA percentage ratio 50:50) and add 90g of dichloromethane, stir to dissolve uniformly, then use an ultrasonic cleaner to disperse well, and stand by. Add 0.02g of Triton X-100 to the solution, stir well to foam, and then place it in a mold with a rectangular flake-shaped groove with a thickness of 1.5cm. Place the mold in a vacuum drying oven at 50℃ and vacuum dry for 12h to volatilize the dichloromethane, then take out the mold and place it in a cooling solidification oven at 30℃ for 12h. Take out the molded material and cut it into a thin slice-shaped degradable (facial filling and shaping) material finished product with a thickness of 3mm according to requirements, which has an average pore size of 45 microns and a porosity of 17%.

[0095] Example 4

[0096] Polylactic acid (PLA) (number average molecular weight 80,000) and polylactic acid-glycolic acid copolymer (LA / GA ratio 50:50) were vacuum dried in a 40℃ vacuum drying oven for 12 hours to remove excess moisture. 16g of the dried PLA and 4g of the dried LA / GA copolymer were weighed and mixed thoroughly, then melt-blended at 185℃ for 20 minutes. The temperature was raised to 200℃, and the molten blend was hot-pressed (pressure 20MPa, time 5 minutes) into sheets. The sheets were placed in a high-pressure reactor at 100℃ and 20MPa, and 0.8g of supercritical CO2 was injected for 2 hours. After removing the material from the reactor, a sheet-like porous biodegradable (facial filling and shaping) material was obtained. The resulting sheet-like porous biodegradable (facial filling and shaping) material had a thickness of 3mm, an average pore size of 35 micrometers, and a porosity of 38%.

[0097] Example 5

[0098] 20g of polylactic acid (number average molecular weight 80,000) granules were placed in a vacuum drying oven at 40℃ to remove moisture for 12 hours. The dried raw material was then melt-extruded and drawn into filaments at 180℃ using a twin-screw extruder at a screw speed of 100 rpm. The filaments were then cooled to 20℃ for curing and, after stretching and traction treatment, obtained as printed filaments. The printing process used was carried out by Envision TEC GmbH, Germany. A 3D printer was used. The print head was aligned parallel to the printing platform. Filament was drawn into the high-temperature print head by rollers, melted, and extruded. The extrusion speed was 3.5 mm / s, the print head temperature was 175°C, and the printing platform temperature was maintained at 90°C. Layer-by-layer printing yielded a shaped material, which was then placed in a 20°C vacuum drying oven to cool and solidify. The oven was then heated to 40°C and vacuum-dried for 24 hours to obtain the final 3D-printed biodegradable (facial filler / shaping) material. The resulting 3D-printed biodegradable (facial filler / shaping) material was a sheet with a thickness of 5 mm, an average pore size of 95 micrometers, and a porosity of 82%.

[0099] Example 6

[0100] Dissolve 15g of polycaprolactone (number average molecular weight 100,000) in dichloromethane to prepare a 15% (w / w) solution. Place the solution in a syringe and let it stand for 1 hour to defoam. Adjust the temperature to 20℃ and perform reciprocating parallel printing layer by layer through the injection needle at an extrusion rate of 10mm / s, ensuring that the path of each layer is consistent. Place the printed material in a vacuum drying oven at 50℃ for 24 hours, and then place it in a room temperature environment for 48 hours to obtain a 3D printed biodegradable (facial filling and shaping) material with an average pore size of 35 micrometers and a porosity of 70%. Cut it into sheets with a thickness of 5mm according to actual needs.

[0101] Application test example

[0102] Biological safety and implantation effect evaluation was performed on the degradable (facial filling plastic) materials of Examples 1-6, and the biological safety and implantation effect evaluation was performed on the clinical use of expanded polytetrafluoroethylene material (Comparative Example 1), the clinical use of silicone filling material (Comparative Example 2), the clinical use of injectable hyaluronic acid material (Comparative Example 3), and the clinical use of injectable polylactic acid microsphere material (Comparative Example 4).

[0103] (1) Cell viability test

[0104] L929 cells were inoculated into the well plate, and the extract of the degradable (facial filling plastic) material of the example and the material of the comparative example was extracted, and then CCK8 was added after the extract was added to the well plate. The cell viability was detected. According to GB / T16886.5-2017h and GB / T16886.4-2003, the cytotoxicity and hemolysis of the implant material were evaluated, and the results are shown in Table 1.

[0105] Table 1

[0106]

[0107] As can be seen from Table 1, the toxicity evaluation of the filling material prepared by the present application on fibroblasts can reach 0 level, which is non-toxic; the hemolysis rate is less than 5%. The cytotoxicity of Comparative Example 2 is 1 level, and the hemolysis rate of Comparative Examples 1 and 2 is higher than 5%, and the blood compatibility is poor. It can be seen that the filling material prepared in the examples of the present application has good biocompatibility and biological safety.

[0108] (2) Degradation rate and tissue filling effect observation

[0109] The implantation experiment was performed according to the method of GB / T16886.6-2015. SD rats, male, 200-220g. The materials of Examples 1-6 and Comparative Examples 1-4 were implanted into the subcutaneous tissue of rats, respectively, and the degradation of the materials was observed at 3 months, 6 months and 12 months after implantation, respectively. The results are shown in Table 2. All rats were photographed before taking samples at 3 sample time points after implantation, and the inflammation and erythema degree was observed. The macroscopic observation of tissue filling effect was performed at 3 months, 6 months and 9 months after implantation, respectively, and the results are shown in Table 3. The tissue ingrowth degree, fibrosis and inflammatory reaction were observed after 12 weeks of material implantation, and the results are shown in Table 4.

[0110] Table 2

[0111]

[0112] Table 3

[0113]

[0114]

[0115] As can be seen from Tables 1-3, the filling material prepared in the embodiment of the present application is implanted into subcutaneous tissue of rats, and has a degradation time of more than 12 months in the tissue; has no obvious adverse reactions such as redness, swelling, subcutaneous nodules, etc.; does not produce sensitization reaction after implantation, and has good filling effect; has good biocompatibility, degradability and tissue integration, and has practical value for clinical application. Although Comparative Example 3 has high biological safety and can be biodegraded, its degradation rate is too fast, and the effect of stimulating regeneration of new tissue is not obvious, so it cannot achieve long-term supporting effect. The material of Comparative Example 4 is also an aliphatic polyester (polylactic acid), but because it is a microspherical material that can be injected, its degradation speed is also fast, and a small amount of nodules will be produced.

[0116] Table 4

[0117]

[0118] The tissue ingrowth degree, fibrosis and inflammatory reaction results of Table 4 show that the embodiments of the present application have no inflammatory reaction and fibrosis, while Comparative Examples 1 and 2 have inflammatory reaction and fibrosis phenomenon to different degrees; Examples 1 and 3 are in the form of thin sheets, have no internal voids or low porosity, and Comparative Example 2 also has no porosity, so the tissue cannot grow in or has low ingrowth degree; Examples 2, 4, 5, 6 and Comparative Examples 1, 3 and 4 contain porosity structure, and can make the tissue grow inside, which can effectively avoid displacement of the implanted body in the later period. However, Comparative Example 1 has low porosity and low tissue ingrowth degree, while Examples 2, 4, 5 and 6 have high porosity, and the tissue can grow in a large amount, and can be degraded, so new tissue continuously grows in during the degradation process, realizes replacement of the material by autologous new tissue, and has good filling safety and effect.

[0119] As can be seen from Examples 1-6, Comparative Examples 1-4 and Tables 1-4, compared with the existing clinical use of expanded polytetrafluoroethylene material, silicone filling material, hyaluronic acid material and polylactic acid microsphere material, the degradable (facial filling and shaping) material with special shape of the present application avoids the defects of the hyaluronic acid material, such as too fast degradation speed, inability to maintain the effectiveness of increasing tissue volume for a long time, too many times of additional filling, complicated process and high price, and avoids the defects of the polytetrafluoroethylene material and the silicone filling material, such as poor blood compatibility, non-degradability, permanent existence in the face and subcutaneous tissue, and causing face stiffness, etc. The degradable (facial filling and shaping) material with special shape of the present application has moderate degradation time in the tissue, up to 12 months or more, no obvious adverse reactions such as redness and swelling, subcutaneous nodules, etc., no sensitization reaction after implantation, and good filling effect. The material of Comparative Example 4 is also an aliphatic polyester (polylactic acid), but since it is an injectable microspherical material, the degradation speed is also fast, a small amount of nodules are produced, and it is not suitable for large size shaping of the face. Therefore, overall, the comprehensive performance of the degradable (facial filling and shaping) material with special structure and adjustable shape of the present application is also superior to the polylactic acid microsphere material of Comparative Example 4.

[0120] Although embodiments of the present application have been shown and described, it is to be understood that various modifications, substitutions, replacements and changes can be made to these embodiments without departing from the principles and spirit of the present application, and the scope of the present application is defined by the appended claims and their equivalents.

Claims

1. A biodegradable material comprising aliphatic polyester and / or modified aliphatic polyester, wherein the biodegradable material is in the form of a sheet with a thickness of 0.1-8 mm, preferably 2-5 mm.

2. The biodegradable material as described in claim 1, characterized in that: The biodegradable material is one or more of the following sheet-like forms: a sheet-like form without internal pores, a sheet-like form containing pores with an average pore size of 30-100 micrometers, preferably a sheet-like form containing pores with an average pore size of 30-100 micrometers; preferably, the porosity of the biodegradable material in the sheet-like form containing pores with an average pore size of 30-100 micrometers is 15-85%, preferably 57-80%; and / or, The aliphatic polyester includes one or more of polylactic acid, polyhydroxyacetic acid, polyhydroxyalkanoate, and polycaprolactone; and / or, The modified aliphatic polyester is obtained by modifying an aliphatic polyester, and the modification method is at least one of chemical grafting, surface modification, copolymerization, physical blending, and coating.

3. A method for preparing a biodegradable material as described in any one of claims 1-2, comprising obtaining the biodegradable material by passing a component including aliphatic polyester and / or modified aliphatic polyester through at least one of solvent evaporation, foaming-solvent evaporation, melt setting, melt foaming, electrospinning, and 3D printing; preferably, the biodegradable material is obtained by passing a component including aliphatic polyester and / or modified aliphatic polyester through at least one of foaming-solvent evaporation, melt foaming, electrospinning, and 3D printing.

4. The preparation method according to claim 3, characterized in that: The solvent evaporation includes: dissolving components including aliphatic polyester and / or modified aliphatic polyester in organic solvent 1, then heating to evaporate organic solvent 1, and finally cooling to solidify to obtain the biodegradable material; preferably, The organic solvent 1 is at least one selected from dichloromethane, trichloromethane, tetrahydrofuran, ethyl acetate, and dimethyl sulfoxide; and / or, The mass concentration of the solution obtained by dissolving the components, including aliphatic polyesters and / or modified aliphatic polyesters, in organic solvent 1 is 0.1-30%, preferably 5-10%; and / or, The temperature at which the organic solvent 1 evaporates is 30-90°C; and / or, The cooling and curing temperature is 5-25℃, and the cooling and curing time is 2-24h.

5. The preparation method according to claim 3, characterized in that: The foaming-solvent evaporation process includes: dissolving components including aliphatic polyester and / or modified aliphatic polyester in organic solvent 2, then adding surfactant and / or foaming agent, stirring and foaming, placing the mixture in a mold, placing the mold under vacuum and heating to evaporate the organic solvent 2, and then cooling and curing to obtain the biodegradable material; preferably, The organic solvent 2 is at least one selected from dichloromethane, trichloromethane, tetrahydrofuran, ethyl acetate, and dimethyl sulfoxide; and / or, The mass concentration of the solution obtained by dissolving components including aliphatic polyesters and / or modified aliphatic polyesters in organic solvent 2 is 0.1-30%, preferably 5-10%; and / or, The surfactant is at least one of anionic surfactants, cationic surfactants, and amphoteric surfactants, and / or the foaming agent is at least one of sodium carbonate and sodium bicarbonate; and / or, The total mass ratio of the surfactant and foaming agent to the components including aliphatic polyester and / or modified aliphatic polyester is 0.2-1%; and / or, The temperature at which the organic solvent 2 evaporates is 30-90℃, and / or the cooling and curing temperature is 5-35℃, and the cooling and curing time is 6-24h.

6. The preparation method according to claim 3, characterized in that: The melt-setting process includes: melting components including aliphatic polyester and / or modified aliphatic polyester at high temperature, and then obtaining the biodegradable material by hot pressing; preferably, The high-temperature melting temperature is 150-300℃; and / or, The hot pressing temperature is 120-250℃, the pressure is 5-30MPa, and the time is 1-10min.

7. The preparation method according to claim 3, characterized in that: The melt foaming process includes: melting components including aliphatic polyester and / or modified aliphatic polyester, hot-pressing them into sheets, then placing them in an autoclave and injecting supercritical CO2 for a foaming reaction to obtain the biodegradable material; preferably, The hot-pressing temperature is 120-250℃, the pressure is 5-30MPa, and the time is 1-10min; and / or, The operating conditions for the autoclave include: temperature 80-150℃, pressure 5-35MPa; and / or, The amount of supercritical CO2 used is 0.01-20% of the mass of the components including aliphatic polyester and / or modified aliphatic polyester, and / or the foaming reaction time is 0.5-2h.

8. The preparation method according to claim 3, characterized in that: The electrospinning process includes: dissolving components including aliphatic polyester and / or modified aliphatic polyester in organic solvent 3, then performing electrospinning, collecting the spun fibers layer by layer, drying, and curing to obtain the biodegradable material; preferably, The organic solvent 3 is at least one selected from dichloromethane, trichloromethane, tetrahydrofuran, ethyl acetate, and dimethyl sulfoxide; and / or, The mass concentration of the solution obtained by dissolving the components, including aliphatic polyester and / or modified aliphatic polyester, in organic solvent 3 is 0.1-30%, preferably 5-10%.

9. The preparation method according to claim 3, characterized in that: The 3D printing includes at least one of fused deposition modeling (FDM) 3D printing and cryogenic 3D printing; preferably, The fused deposition modeling (FDM) 3D printing includes: placing a component comprising aliphatic polyester and / or modified aliphatic polyester in an extruder for melt extrusion and filament drawing; subsequently, after cooling and curing, and stretching treatment, a filament is obtained; and finally, the filament is printed layer by layer by a 3D printer to obtain the biodegradable material; and / or, The low-temperature 3D printing includes: dissolving components including aliphatic polyester and / or modified aliphatic polyester in organic solvent 4, filling a syringe, and reciprocating layer-by-layer parallel printing through an injection needle to obtain the biodegradable material.

10. Use of an aliphatic polyester and / or modified aliphatic polyester as a facial filler and shaping material, wherein the aliphatic polyester and / or modified aliphatic polyester is in sheet form with a thickness of 0.1-8 mm, preferably 2-5 mm.

11. The use as described in claim 10, characterized in that: The aliphatic polyester and / or modified aliphatic polyester are one or more of the following sheet-like forms: sheet-like with no internal pores, sheet-like with pores having an average pore size of 30-100 micrometers, preferably sheet-like with pores having a pore size of 30-100 micrometers; preferably, the porosity of the aliphatic polyester and / or modified aliphatic polyester in the sheet-like form with pores having an average pore size of 30-100 micrometers is 15-85%, preferably 57-80%; and / or, The aliphatic polyester includes one or more of polylactic acid, polyhydroxyacetic acid, polyhydroxyalkanoate, and polycaprolactone; and / or, The modified aliphatic polyester is obtained by modifying an aliphatic polyester, and the modification method is at least one of chemical grafting, surface modification, copolymerization, physical blending, and coating.

12. The use as described in any one of claims 10-11, characterized in that: The aliphatic polyester and / or modified aliphatic polyester in sheet form is obtained by at least one of the following methods: solvent evaporation, foaming-solvent evaporation, melt setting, melt foaming, electrospinning, and 3D printing. Preferably, the aliphatic polyester and / or modified aliphatic polyester in sheet form is obtained by at least one of the following methods: foaming-solvent evaporation, melt foaming, electrospinning, and 3D printing.

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