Polyester staple fiber-microsphere composite medical filling material as well as preparation method and application thereof

Abstract

The invention provides a composite composition containing polyester staple fibers and polyester microspheres and application of the composite composition as a medical beauty filling material. The invention also provides a method for preparing the polyester staple fiber. The invention provides a brand-new medical beauty filling material solution by utilizing good biocompatibility, biodegradability and unique linear structure after the polyester staple fibers and the microspheres are compounded.

Description

(19) State Intellectual Property Office (12) Invention Patent Application (10) Application Publication Number (43) Application Publication Date (21) Application Number 202511573530.X (22) Application Date 2025.10.30 (71) Applicant Beijing Puri Biotechnology Co., Ltd. Address Room A209, 2nd Floor, No. 5, Kaituo Road, Haidian District, Beijing 100085 (72) Inventor Lu Yunfeng (74) Patent Agency Beijing Zhongzi Law Firm 11247 Patent Attorneys Chen Runjie and Huang Gesheng (51) Int.Cl. D01D 5 / 08 (2006.01) A61K 8 / 85 (2006.01) A61Q 19 / 08 (2006.01) A61L 27 / 26 (2006.01) A61L 27 / 58 (2006.01) D01F 6 / 62 (2006.01) D01G 1 / 04 (2006.01) (54) Invention Title: A Polyester Short Fiber-Microsphere Composite Medical Filler Material and Its Preparation Method and Application (57) Abstract: This disclosure provides a composite composition comprising polyester short fibers and polyester microspheres and its application as a medical aesthetic filler material. This disclosure also provides a method for preparing polyester short fibers. This disclosure utilizes the good biocompatibility, biodegradability, and unique linear structure of polyester short fibers and microspheres to provide a novel medical aesthetic filler material solution. Claims (2 pages), Description (12 pages), Drawings (4 pages), CN 121473010 A 2026.02.06 CN 1 21 47 30 10 A 1. A method for preparing polyester staple fibers, comprising the following steps: S1, preparing polyester continuous fiber material from polyester raw materials by melt spinning or solution spinning; S2, freezing and fixing the continuous fiber material obtained in step S1 in the presence of an embedding agent; S3, freezing and slicing the fixed material obtained in step S2 to obtain staple fiber slices of a certain size; and optionally S4, post-processing the staple fiber slices obtained in step S3. 2. The method of claim 1, wherein step S1 is carried out by melt spinning, wherein the polyester raw material is selected from one or more of polylactic acid (PLA), poly-L-lactide (PLLA), poly(ε-caprolactone) (PCL), polyvalerol (PVL), polyglycolic acid (PGA), polylactic acid-glycolic acid (PLGA) copolymer, and polyhydroxybutyrate (PHB), and / or heated at a temperature of about 200-250°C, and / or spun using a spinneret with an aperture of about 200-400 μm, and / or cooled at about 20-25°C. 3. The method of claim 1 or 2, wherein the diameter of the continuous polyester fiber material obtained in step S1 is about 1-50 μm, for example, about 2-20 μm.4. The method of any one of claims 1-3, wherein the embedding agent in step S2 is an OCT embedding agent or an aqueous solution of a PEG and PVA blend, and / or the freezing conditions are freeze-fixation at about -30 to -20°C for about 0.5 to 1.5 hours. 5. The method of any one of claims 1-4, wherein in step S3, the length of the short fiber slices is about 5 to 300 μm, for example, about 80 to 250 μm. 6. The method of any one of claims 1-5, wherein in step S4, the short fiber slices are washed with an aqueous solvent, centrifuged at about 5000 to 15000 rpm for about 2 to 10 minutes, and dried for about 20 to 30 hours. 7. A biomedical composite composition comprising polyester staple fibers and polyester microspheres, and optionally one or more pharmaceutical excipients, wherein the polyester staple fibers have a fiber diameter ranging from about 1 to 50 μm, for example, about 2 to 20 μm, and a length of about 5 to 300 μm; preferably, the polyester staple fibers have a fiber diameter ranging from about 2 to 15 μm, 2 to 10 μm, or 5 to 10 μm, and a length of about 50 to 250 μm or 80 to 250 μm. 8. The biomedical composite composition of claim 7, wherein the polyester staple fibers are polyester staple fibers prepared according to the method of any one of claims 1 to 6. 9. The biomedical composite composition of claim 7 or 8, wherein the polyester microspheres are selected from one or more of PLA microspheres, PCL microspheres, PLGA microspheres, and PGA microspheres, preferably PLA microspheres, and / or the polyester microspheres have a diameter of about 1 to 200 μm, for example, about 20 to 60 μm. 10. The biomedical composite composition of any one of claims 7-9, wherein the mass ratio of the polyester microspheres to the polyester short fibers is about 50:1 to 1:50, for example about 5:1 to 2:1, for example about 5:1 to 3:1. 11. The biomedical composite composition of any one of claims 7-10, wherein the total content of the polyester short fibers and polyester microspheres is about 2-30%, preferably about 2-5%. 12. The biomedical composite composition of any one of claims 7-11, which is in the form of an injection solution, further comprising a thickener, a filler carrier, a buffer, and an injection medium; preferably further comprising sodium carboxymethyl cellulose, hyaluronic acid, mannitol, and water for injection.13. The biomedical composite composition according to any one of claims 7-12, wherein the diameter of the PLA short fibers ranges from about 2-15 μm, 2-10 μm, or 5-10 μm, and the length is about 50-250 μm or 80-250 μm; the mass ratio between PLA microspheres and PLA short fibers is about 5:1 to 2:1, preferably about 5:1 to 3:1; the mass percentage of PLA microspheres and PLA short fibers is about 2-10%, preferably about 2-5%; the mass percentage of sodium carboxymethyl cellulose is about 2-10%, preferably about 2-6%; the mass percentage of hyaluronic acid is about 0.5-5%, preferably about 0.5-3%; the mass percentage of mannitol is about 10-20%, preferably about 10-15%; and the mass percentage of water for injection is about 60-90%, preferably about 75-85%. 14. The use of polyester staple fibers prepared according to any one of claims 1-6, alone or in combination with other materials, for medical aesthetic purposes, such as for promoting collagen formation, for example for skin rejuvenation or anti-skin aging, such as improving wrinkles and fine lines, enhancing skin firmness, improving skin texture and radiance, or for medical aesthetic filling such as soft tissue filling and contouring, or for skin repair or regeneration, or as a collagen stimulant in combination with other medical aesthetic procedures. 15. The use of the biomedical composite composition according to any one of claims 7-13 for medical aesthetic purposes, such as for promoting collagen formation, for example for skin rejuvenation or anti-skin aging such as improving wrinkles and fine lines, enhancing skin firmness, improving skin texture and radiance, or for medical aesthetic filling such as soft tissue filling and contouring, or for skin repair or regeneration, or as a collagen stimulant in combination with other medical aesthetic procedures. 16. Use of the polyester staple fiber prepared according to any one of claims 1-6 or the biomedical composite composition according to any one of claims 7-13 in the preparation of biomedical materials for medical aesthetics, for example, for promoting collagen production, specifically for skin rejuvenation or anti-skin aging such as improving wrinkles and fine lines, enhancing skin firmness, improving skin texture and radiance, or for medical aesthetic filling such as soft tissue filling and contouring, or for skin repair or regeneration, or as a collagen stimulant used in combination with other medical aesthetic procedures. 17. A method for promoting collagen formation, comprising applying the biomedical composite composition according to any one of claims 7-13 to an individual in need. 18. A medical aesthetic method, specifically a skin rejuvenation or anti-skin aging method such as improving wrinkles and fine lines, enhancing skin firmness, improving skin texture and radiance, or a medical aesthetic filling method such as soft tissue filling and contouring, or a method for skin repair or regeneration, comprising applying the biomedical composite composition according to any one of claims 7-13 to an individual in need.Claims 2 / 2 Page 3 CN 121473010 A Polyester Short Fiber-Microsphere Composite Medical Filler Material and Its Preparation Method and Application Technical Field

[0001] This disclosure belongs to the field of biomedical materials, specifically relating to a composition comprising polyester short fibers and polyester microspheres, its preparation method, and its application in preparing medical aesthetic filler materials using this composite as the main functional material. Background Art

[0002] With the rapid development of modern medical aesthetic technology, soft tissue filling treatment has become an important means of non-surgical cosmetic procedures. In the prior art, materials used for soft tissue filling mainly include hyaluronic acid, collagen, and polyester materials. Among them, hyaluronic acid currently dominates the field of medical aesthetic filler due to its good biocompatibility and degradability. However, hyaluronic acid is easily degraded by hyaluronidase in the human body, and its maintenance effect is usually only 3-12 months, belonging to temporary filler materials. This characteristic leads to patients needing to undergo repeated injection treatments frequently, which not only increases the economic burden on patients but also brings the inconvenience of repeated medical operations. Collagen, as another commonly used filler material, can provide a relatively natural filling effect, but it carries the risk of inducing allergic reactions. Some patients may also experience adverse reactions such as granuloma formation, limiting the safety of its clinical application.

[0003] Polyester materials, such as polylactic acid (PLA), polycaprolactone (PCL), and polylactic-glycolic acid copolymer (PLGA), have been widely used in the medical field due to their excellent biocompatibility and controllable biodegradability. In the field of cosmetic fillers, polyester materials are usually applied in the form of microspheres. Their mechanism of action is mainly to stimulate macrophages and fibroblasts in local tissues, promoting the synthesis and secretion of endogenous collagen, thereby improving skin texture and achieving a relatively long-lasting cosmetic effect. However, due to the limitations of their spherical geometry, the effect of polyester microspheres in the prior art in stimulating collagen production still needs further improvement. The contact area between spherical microspheres and cells is relatively limited, and their surface morphology lacks sufficient cell adhesion sites, making it difficult to fully activate the proliferation of fibroblasts and the secretion of collagen. Other polyester filler materials, such as fibrous, sheet-like, or irregularly shaped ones, can clog needles during injection, causing difficulties in injection and pain for patients.

[0004] Therefore, there is an urgent need to develop a new type of medical aesthetic filler material that can maintain the inherent biocompatibility and controllable degradation characteristics of polyester materials, while significantly enhancing the stimulation effect on collagen production through innovative morphological design.Summary of the Invention

[0005] In view of the above-mentioned defects and existing needs of the prior art, the inventors have innovatively designed the morphology of the material and prepared polyester short fibers with uniform diameter and suitable length using a specific preparation process. These fibers are then compounded with polyester microspheres in a suitable dispersion system to obtain an injectable formulation of polyester fiber and polyester microsphere composite. This formulation provides a novel medical aesthetic filler material solution. Utilizing the good biocompatibility, biodegradability, and unique morphological combination of the polyester short fibers and microspheres, it can be uniformly distributed in the dispersion medium, has good injectability, and can also exhibit better biodegradability in vivo, which is more conducive to fibroblast adhesion, thereby better promoting collagen formation. Therefore, the composite provided by this disclosure is expected to break through the bottleneck of collagen stimulation efficiency in existing medical aesthetic filler materials, and provide a more effective technical solution for the field of medical aesthetic fillers.

[0006] Therefore, in a first aspect, this disclosure provides a method for preparing polyester short fibers, comprising the following steps: Specification 1 / 12 page 4 CN 121473010 A

[0007] S1. Preparing polyester continuous fiber material from polyester raw materials by melt spinning or solution spinning;

[0008] S2. Freezing and fixing the continuous fiber material obtained in step S1 in the presence of an embedding agent;

[0009] S3. Freezing and slicing the material fixed in step S2 to obtain short fiber slices of a certain size; and optionally

[0010] S4. Post-processing the short fiber slices obtained in step S3.

[0011] In a second aspect, this disclosure provides a biomedical composite composition comprising polyester short fibers (preferably polyester short fibers prepared by the method of this disclosure) and polyester microspheres; specifically, wherein the polyester short fibers have a fiber diameter ranging from about 2 to 20 μm and a length of about 5 to 300 μm.

[0012] In a third aspect, this disclosure provides a method for preparing a biomedical composite composition, comprising mixing polyester staple fibers (preferably prepared according to the first aspect of this disclosure) with polyester microspheres and optionally one or more pharmaceutical excipients.

[0013] In a fourth aspect, this disclosure provides the use of the polyester staple fibers of this disclosure or the biomedical composite composition of this disclosure in promoting collagen formation, or in the preparation of biomedical materials for promoting collagen formation.

[0014] In a fifth aspect, this disclosure provides the use of the polyester staple fibers of this disclosure or the biomedical composite composition of this disclosure in medical aesthetics, specifically for skin rejuvenation or anti-skin aging, such as improving wrinkles and fine lines, enhancing skin firmness, improving skin texture and radiance, or for medical aesthetic filling such as soft tissue filling and contouring, or for skin repair or regeneration, or as a collagen stimulant used in combination with other medical aesthetic procedures.

[0015] In a sixth aspect, this disclosure also provides the use of the polyester staple fibers of this disclosure or the biomedical composite compositions of this disclosure in the preparation of biomedical materials for medical aesthetics, specifically for skin rejuvenation or anti-skin aging, such as improving wrinkles and fine lines, enhancing skin firmness, improving skin texture and radiance, or for medical aesthetic filling such as soft tissue filling and contouring, or for skin repair or regeneration, or as a collagen stimulant used in combination with other medical aesthetic procedures.

[0016] In a seventh aspect, this disclosure provides a method for promoting collagen formation, comprising applying the biomedical composite compositions of this disclosure to an individual in need.

[0017] In an eighth aspect, this disclosure provides a medical aesthetic method, specifically for skin rejuvenation or anti-skin aging, such as improving wrinkles and fine lines, enhancing skin firmness, improving skin texture and radiance, or for medical aesthetic filling such as soft tissue filling and contouring, or for skin repair or regeneration, comprising applying the biomedical composite compositions of this disclosure to an individual in need.

[0018] Figure 1 is a scanning electron microscope (SEM) image of the continuous PLA fibers obtained in step S1 of the embodiment.

[0019] Figure 2 is a scanning electron microscope (SEM) image of the short PLA fibers prepared in the embodiment.

[0020] Figure 3 is a scanning electron microscope (SEM) image of the PLA microspheres used in the application example.

[0021] Figure 4 is an optical microscope photograph of the injection solution obtained in the application example.

[0022] Figure 5 shows the injection force curves and average injection force data of the injection solutions obtained in Application Examples 1, 2, and 3.

[0023] Figure 6 shows the cytotoxicity of the injection solutions obtained in the application examples at different concentrations.

[0024] Figure 7 shows the H&E, Masson, and Sirius red staining results of the tissue in the injection area 28 days after the injection solutions obtained in Application Examples 2-7 were injected subcutaneously into rats. Detailed Description of the Invention

[0025] Definitions

[0026] The terms “a,” “an,” “the,” and similar terms used herein, and in the context of this disclosure (especially in the context of the claims on page 2 / 12 of the specification, CN 121473010 A), shall be construed as covering both the singular and the plural, unless otherwise stated herein or clearly contradicted by the context.

[0027] The term “about” as used herein will fluctuate by ±10% for numerical values ​​used with it, more specifically by ±5%. With respect to proportions, the term “about” is used to define each number of a given proportion. For example, a proportion of about 1:1 means a proportion of 0.9 to 1.1: 0.9 to 1.1.

[0028] The term “individual” as used herein refers to a primate and is not limited to a specific age or sex. In specific embodiments, the individual being referred to is a human being, including children, adolescents, or adults.

[0029] The term "promoting collagen formation" as used herein refers to materials that, through one or more methods, create favorable conditions for the synthesis, deposition, or stabilization of collagen, thereby leading to an increase in the net collagen content.

[0030] The term "cosmetic medicine" as used herein refers to a branch of medicine that uses drugs, surgery, medical devices, and other invasive or traumatic medical techniques to repair and reshape the shape of various parts of the human body in order to maintain, repair, and reshape the body contour.

[0031] The term "cosmetic filler" as used herein refers to a minimally invasive cosmetic procedure that uses injected or implanted materials to immediately increase the volume of soft tissue to fill depressions, smooth wrinkles, shape or repair contours, etc., to achieve normalization, rejuvenation, or beautification of facial or body contours.

[0032] The term "polyester" or "polyester-based materials" as used herein refers to aliphatic polyesters suitable for use in the pharmaceutical field, mainly made of hydroxy acids or their derivatives such as lactones through condensation or ring-opening polymerization, and which are biocompatible and biodegradable in vivo. Representative polyesters of this type include, but are not limited to, polylactic acid (PLA), poly-L-lactide (PLLA), poly(ε-caprolactone) (PCL), polyvalerol (PVL), polyglycolic acid (PGA), polylactic acid-glycolic acid (PLGA) copolymer, and polyhydroxyalkanoates (PHA) such as polyhydroxybutyrate (PHB).

[0033] The term “polyester staple fiber” as used herein refers to fibrous materials made of polyester polymers that are relatively short in length (typically a few micrometers to tens of millimeters).

[0034] The term “melt spinning” as used herein refers to a chemical fiber spinning method in which polymer raw materials are heated to a molten state, extruded through spinnerets, and rapidly cooled and solidified in air or water to form fibers.

[0035] As used herein, the term "solution spinning" refers to a spinning method in which a polymer raw material is dissolved in a solvent to prepare a spinning solution of suitable concentration, and then the spinning solution is extruded through micropores into a coagulation bath (wet process) or a hot gas (dry process), whereby the polymer precipitates into solid fibers.

[0036] As used herein, the term "microsphere" refers to a spherical particle composed of natural or synthetic polymer materials with a size between about 1 and 1000 μm, more typically between about 1 and 250 μm. In the pharmaceutical field, microspheres are commonly used as drug delivery systems or fillers. The term "polyester microsphere" as used herein refers to microspheres made of biodegradable aliphatic polyester materials, such as microspheres made of "polyester" as defined herein, such as PLA microspheres, PLGA microspheres, PCL microspheres, etc.

[0037] As used herein, the term "pharmaceutical excipient" means a substance that can be used in the preparation or use of a medical composition, such as suitable diluents, solvents, dispersion media, surfactants, antioxidants, preservatives, isotonic agents, buffers, suspending agents, thickeners, fillers, and combinations thereof, as known to those skilled in the art (see, for example, Remington, The Science and Practice of Pharmacy, 22nd Ed. Pharmaceutical Press, 2013, pp. 1049-1070).

[0038] Technical and scientific terms not specifically defined herein have the meanings commonly understood by those skilled in the art to which this invention pertains.

[0039] All methods described herein may be performed in any suitable order unless otherwise stated herein or obviously contradicted by the context. The use of any and all embodiments or exemplary language (e.g., "as") provided herein is intended only to better illustrate this disclosure and does not constitute a limitation on the scope of the additionally claimed disclosure.

[0040] This disclosure provides a method for preparing and compounding polyester short fibers and polyester microspheres, and their application as a medical aesthetic filler material, to further improve the collagen-stimulating effect of existing medical aesthetic fillers. The method precisely controls the diameter and length of the fibers, ensuring high uniformity and excellent physical properties while combining the morphological characteristics of both microspheres and fibers. This ensures that the short fibers can be smoothly injected through a 27G or higher injection needle, while simultaneously achieving a synergistic promoting effect of short fibers and microspheres on collagen formation.

[0041] In one aspect, this disclosure provides a method for preparing polyester staple fibers, comprising the following steps:

[0042] S1, preparing polyester raw materials into continuous polyester fiber materials by melt spinning or solution spinning processes;

[0043] S2, freezing and fixing the continuous fiber material obtained in step S1 in the presence of an embedding agent;

[0044] S3, freezing and slicing the material fixed in step S2 to obtain staple fiber slices of a certain size; and optionally

[0045] S4, performing post-processing on the staple fiber slices obtained in step S3.

[0046] In some embodiments, the polyester raw materials used in step S1, as defined herein, are preferably selected from one or more of polylactic acid (PLA), poly-L-lactide (PLLA), poly(ε-caprolactone) (PCL), polyvalerol (PVL), polyglycolic acid (PGA), polylactic acid-glycolic acid (PLGA) copolymers, polyhydroxyalkanoates (PHA) such as polyhydroxybutyrate (PHB), and more preferably polylactic acid (PLA).

[0047] In some embodiments, step S1 is performed using a melt spinning process. The melt spinning process may specifically include the following steps: adding polyester raw materials into the barrel of an extruder such as a screw extruder, melting and plasticizing them at a certain temperature, then conveying the melt to a spinneret via a metering pump, and cooling the nascent fibers obtained by spinning in an air or inert gas environment before winding and stretching to obtain continuous fibers.

[0048] In some embodiments, step S1 may be performed using a solution spinning process. The solution spinning process may specifically include the following steps: dissolving polyester raw materials in a suitable solvent to prepare a spinning solution, filtering and degassing the solution, and then conveying the spinning solution to a spinneret via a metering pump. The nascent fibers obtained by spinning are solidified in a coagulation bath, then washed with water to remove residual solvent, and then wet-stretched (wet method), or solidified by evaporating the solvent in hot air (dry method), and then dried and wound to obtain continuous fibers.

[0049] In some embodiments, in step S1, the heating temperature for melt plasticization in the melt spinning process varies depending on the polymer material, and is generally about 100~300°C, for example about 100~250°C, 150~250°C, 180~250°C, 200~240°C, 220~240°C; preferably about 200~250°C.

[0050] In some embodiments, in step S1, the orifice diameter of the spinneret in the melt spinning process is about 100~500 μm, for example about 200~500 μm, about 200~400 μm, about 100~250 μm, for example about 300 μm.

[0051] In some embodiments, in step S1, the aspect ratio (length to diameter ratio L / D) of the spinneret in the melt spinning process is about (2~10):1, for example, about 2:1 to 10:1, about 2:1 to 8:1, about 2:1 to 6:1, about 2:1 to 5:1, about 2:1 to 4:1, about 2:1 to 3:1, for example, about 2:1, 2.5:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1; preferably about 8:1.

[0052] In some embodiments, in step S1, the cooling temperature of the resulting nascent fiber is about 10~30°C, for example, about 15~25°C, 18~22°C, about 20~25°C, for example, about 25°C.

[0053] In some embodiments, in step S1, the resulting nascent fibers are cooled in an inert gas environment selected from nitrogen, argon, or carbon dioxide, preferably in nitrogen.

[0054] In some embodiments, in step S1, the diameter of the resulting polyester continuous fiber material is about 1 to 50 μm, for example about 1 to 40 μm, 1 to 30 μm, 2 to 20 μm, for example about 2 to 15 μm, 5 to 15 μm, 2 to 10 μm.In some embodiments, in step S1, the crystallinity of the polyester continuous fiber material is about 1 to 60%, for example, about 5 to 60%, about 5 to 50%, about 5 to 40%, about 5 to 30%, about 5 to 20%, about 10 to 60%, about 10 to 50%, about 10 to 40%, about 10 to 30%, about 10 to 20%, about 20 to 60%, about 20 to 50%, about 20 to 40%, about 20 to 30%, about 30 to 60%, about 30 to 50%, about 30 to 40%, about 40 to 60%, about 40 to 50%. This crystallinity can be determined by differential scanning calorimetry, X-ray diffraction, or density gradient method, which are well known to those skilled in the art.

[0056] In some embodiments, in step S1, the elastic modulus of the polyester fiber material is about 2 to 8 GPa, for example, about 2 to 6 GPa, about 3 to 6 GPa, or about 4 to 8 GPa. This elastic modulus can be determined using methods well known to those skilled in the art, such as tensile testing, bending testing, etc.

[0057] In some embodiments, in step S2, the freezing temperature is about -80 to -5°C, for example, it can be about -80 to -10°C, -70 to -10°C, -60 to -10°C, -50 to -10°C, -40 to -10°C, -30 to -10°C, -20 to -10°C, -80 to -20°C, -70 to -20°C, -60 to -20°C, -50 to -20°C, -40 to -20°C, -30 to -20°C, -80 to -30°C, -70 to -30°C, -60 to -30°C, -50 to -30°C, -40 to -30°C; preferably about -30 to -20°C.

[0058] In some embodiments, in step S2, the freezing time is about 0.5 to 5 hours, for example, about 0.5 to 4.5 hours, 0.5 to 4 hours, 0.5 to 3.5 hours, 0.5 to 3 hours, 0.5 to 2.5 hours, 0.5 to 2 hours, 0.5 to 1.5 hours, 0.5 to 1 hour, 1 to 5 hours, 1 to 4.5 hours, 1 to 4 hours, 1 to 3.5 hours, 1 to 3 hours, 1 to 2.5 hours, 1 to 2 hours, 1 to 1.5 hours, 2 to 5 hours, 2 to 4.5 hours, 2 to 4 hours, 2 to 3.5 hours, 2 to 3 hours, 2 to 2.5 hours, 3 to 5 hours, 3 to 4.5 hours, 3 to 4 hours; preferably about 0.5 to 1.5 hours, for example, about 1 hour.

[0059] In some embodiments, in step S2, the embedding agent is a reagent commonly used in immunohistochemistry experiments to support tissue, increase tissue continuity, and reduce wrinkles and fragmentation during frozen sections. Typically, it is an OCT embedding agent, i.e., an aqueous solution of a blend of PEG and PVA, which is commercially available, such as SAKURA, or can be replaced by Tissue-Tek® Cryomold Compound, Cryo-Gel™, Neg-50™, gelatin solution, or sodium carboxymethyl cellulose solution.

[0060] In some embodiments, in step S3, the thickness of the short fiber slice is about 5 to 300 μm, for example, about 10 to 300 μm, 20 to 300 μm, 30 to 300 μm, 40 to 300 μm, 50 to 300 μm, 60 to 300 μm, 70 to 300 μm, 80 to 300 μm, 100 to 300 μm, 5 to 250 μm, 50 to 250 μm, 80 to 250 μm, 100 to 250 μm, 150 to 250 μm; preferably about 80 to 250 μm.

[0061] In some embodiments, in step S3, the short fiber slice can be prepared using methods well known to those skilled in the art, for example, using a commercially available cryostat, such as the ZD-LQ3300 or a series of Leica Biosystems cryostats.

[0062] In some embodiments, the method for preparing polyester staple fibers of this disclosure further includes step S4, wherein the staple fibers obtained in step S3 are post-treated, specifically including washing, centrifugation, and drying.

[0063] In some embodiments, in step S4, the washing step is performed using a suitable solvent to remove impurities, such as water, methanol, ethanol, ethylene glycol, isopropanol, preferably water.

[0064] In some embodiments, in step S4, the centrifugation speed of the centrifugation step is about 2000 to 20000 rpm, for example about 5000 to 20000 rpm, 5000 to 15000 rpm, or 8000 to 12000 rpm; preferably about 10000 rpm.

[0065] In some embodiments, in step S4, the centrifugation separation step is performed for about 1 to 20 minutes, for example, about 1 to 15 minutes, 1 to 10 minutes, 1 to 8 minutes, 2 to 20 minutes, 2 to 15 minutes, 2 to 10 minutes, or 2 to 8 minutes; preferably about 5 minutes.

[0066] In some embodiments, in step S4, the drying time is about 5 h to 48 h, for example, about 5 to 40 h, 5 to 35 h, 5 to 30 h, 5 to 25 h, 10 to 48 h, 10 to 40 h, 10 to 30 h, 15 to 48 h, 15 to 40 h, 15 to 30 h, 20 to 48 h, 20 to 40 h, 20 to 30 h; preferably about 20 to 30 h, for example, about 20 to 25 h, for example, about 24 h.

[0067] In some embodiments, in step S4, the drying temperature is 30 to 60°C. Specification 5 / 12 pages 8 CN 121473010 A

[0068] It should be noted that the method for preparing polyester staple fibers disclosed herein includes any combination of the specific or preferred features of any of the above steps and the specific or preferred features of one or more other steps to obtain the method technical solution.

[0069] In a specific embodiment, this disclosure provides a method for preparing polyester staple fibers, comprising the following steps:

[0070] S1' Preparing polyester raw materials into continuous polyester fiber materials by melt spinning, wherein the polyester raw materials are selected from one or more of polylactic acid (PLA), poly-L-lactide (PLLA), poly(ε-caprolactone) (PCL), polyvalve lactone (PVL), polyglycolic acid (PGA), polylactic acid-glycolic acid (PLGA) copolymer, and polyhydroxybutyrate (PHB), wherein the fibers are spun at a temperature of about 200-250°C using a spinneret with an aperture of about 200-400 μm, and cooled at about 20-25°C, resulting in a continuous polyester fiber material with a diameter of about 2-20 μm;

[0071] S2' Freezing and fixing the continuous fiber material obtained in step S1 at about -30--20°C for about 0.5-1.5 hours in the presence of an OCT embedding agent;

[0072] S3' Freeze-slice the material fixed in step S2 to obtain short fiber slices with a length of approximately 80-250 μm; and

[0073] S4' Wash the short fiber slices obtained in step S3 with an aqueous solvent, centrifuge at approximately 5000-15000 rpm for approximately 2-10 minutes, and dry for approximately 20-30 hours.

[0074] It should be noted that the characteristics of each step in this specific method embodiment can also be independently defined by more specific or preferred values ​​for each step characteristic above.

[0075] In a second aspect, this disclosure provides a biomedical composite composition comprising polyester short fibers and polyester microspheres. In a specific embodiment, the polyester short fibers in the biomedical composite composition of this disclosure are polyester short fibers prepared according to the method of the first aspect of this disclosure, as generally or specifically defined in this disclosure.

[0076] In some embodiments, the polyester short fibers in the biomedical composite composition of this disclosure have a fiber diameter range of about 1 to 50 μm and a length of about 5 to 300 μm; specifically, they may be the corresponding general or specific ranges defined by the method technical solution of the first aspect of this disclosure, for example, the fiber diameter range may be about 2 to 20 μm, 2 to 15 μm, 2 to 10 μm, 5 to 10 μm, and the length may be about 50 to 250 μm, 80 to 250 μm.

[0077] In the biomedical composite composition of this disclosure, the polyester microspheres included are microspheres made of biodegradable aliphatic polyester materials, such as one or more of PLA microspheres, PCL microspheres, PLGA microspheres, and PGA microspheres; in one specific embodiment, the polyester microspheres included are PLA microspheres.

[0078] In the biomedical composite composition of this disclosure, the polyester microspheres included are commercially available or can be obtained by those skilled in the art using microsphere preparation methods well known in the art.

[0079] In the biomedical composite composition of this disclosure, the diameter of the included polyester microspheres is between about 1 and 200 μm, more typically between about 1 and 150 μm, and preferably between about 20 and 60 μm.

[0080] In some embodiments, in the biomedical composite composition of this disclosure, the mass ratio of polyester microspheres to polyester short fibers is about 50:1 to 1:50, for example about 40:1 to 1:40, 30:1 to 1:30, 20:1 to 1:20, 10:1 to 1:10, 5:1 to 1:5, and for example about 5:1 to 2:1, for example about 5:1 to 3:1, for example about 5:1, about 4:1, about 3:1 or about 2:1, at which ratio the composition in injectable form can be readily injected through a 27G needle.

[0081] In some embodiments, the biomedical composite composition of this disclosure comprises about 2-30% by mass of polyester staple fibers and polyester microspheres, for example about 2-30%, 2-20%, 2-10%, 2-8%, 3-20%, 3-10%, 3-8%, preferably about 2-10%, 2-8%, 2-5%, for example about 3%.

[0082] In some embodiments, the biomedical composite composition of this disclosure is an injectable preparation, for example, a lyophilized injectable preparation, wherein, in addition to the polyester staple fibers and polyester microspheres, it optionally contains one or more pharmaceutically acceptable excipients, such as, but not limited to, thickeners or suspending agents, filler carriers, buffers and / or injection media.

[0083] In some embodiments, the injectable biomedical composite composition of this disclosure contains a thickener or suspending agent to, for example, prevent the microspheres or staple fibers from settling.Suitable thickeners or suspending agents include, but are not limited to, sodium carboxymethyl cellulose, hydroxyethyl cellulose, and sodium alginate, with sodium carboxymethyl cellulose being preferred.

[0084] In some embodiments, the injectable biomedical composite composition of this disclosure contains about 1 to 40% by weight of a thickener or suspending agent, such as about 1 to 40%, 1 to 30%, 1 to 20%, 1 to 10%, 2 to 10%, 2 to 8%, 2 to 6%, preferably about 2 to 10%, 2 to 6%, or 3 to 5%.

[0085] In some embodiments, the injectable biomedical composite composition of this disclosure includes a filler carrier to, for example, provide a suitable hydration environment immediately and prevent microsphere aggregation. Suitable filler carriers include, but are not limited to, hyaluronic acid, chondroitin sulfate, polyglutamic acid, and collagen solutions, with hyaluronic acid having a molecular weight of 200,000 to 1,000,000 Da being preferred, and hyaluronic acid having a molecular weight of about 300,000 Da being preferred.

[0086] In some embodiments, the injectable biomedical composite composition of this disclosure contains about 0.5 to 40% by weight of a filler carrier, such as about 0.5 to 40%, 0.5 to 20%, 0.5 to 10%, 0.5 to 5%, 0.5 to 3%, 1 to 20%, 1 to 10%, 1 to 5%, 1 to 3%, preferably about 0.5 to 5%, 0.5 to 3%, 1 to 2%.

[0087] In some embodiments, the injectable biomedical composite composition of this disclosure contains a buffer to, for example, adjust the osmotic pressure of the injection and / or provide lyophilization protection. Suitable buffers include, but are not limited to, mannitol, sucrose, trehalose, glycine, sorbitol, etc., with mannitol being preferred.

[0088] In some embodiments, the injectable biomedical composite composition of this disclosure contains about 1 to 30% by weight of a buffer, such as about 1 to 25%, 1 to 20%, 1 to 15%, 5 to 30%, 5 to 20%, 5 to 15%, 10 to 30%, 10 to 25%, 10 to 20%, 10 to 15%, preferably about 10 to 20%, 10 to 15%, or 10 to 13%.

[0089] In some embodiments, the injectable biomedical composite composition of this disclosure contains an injection medium, such as sterile water for injection.

[0090] In some embodiments, the injectable biomedical composite composition of this disclosure contains about 60 to 90% by weight of an injection medium, such as about 70 to 90%, or 75 to 85%.

[0091] In some embodiments, the injectable biomedical composite composition of this disclosure, in addition to polyester staple fibers and polyester microspheres of the types and amounts generally or specifically defined in this disclosure, also includes a thickener of the types and amounts generally or specifically defined in this disclosure, a filler carrier of the types and amounts generally or specifically defined in this disclosure, a buffer of the types and amounts generally or specifically defined in this disclosure, and an injection medium of the types and amounts generally or specifically defined in this disclosure; in more specific embodiments,

[0092] the diameter of the polyester staple fibers ranges from about 1 to 50 μm, for example about 2 to 15 μm, 2 to 10 μm, or 5 to 10 μm, and the length is about 50 to 250 μm or 80 to 250 μm;

[0093] the mass ratio between polyester microspheres and polyester staple fibers is about 50:1 to 1:50, for example about 5:1 to 2:1, for example about 5:1 to 3:1;

[0094] the mass percentage of polyester staple fibers and polyester microspheres is about 2 to 10%, for example about 2 ~ 5%;

[0095] The mass percentage of the thickener is about 2 to 10%, for example, about 2 to 6%;

[0096] The mass percentage of the filler carrier is about 0.5 to 5%, for example, about 0.5 to 3%;

[0097] The mass percentage of the buffer is about 10 to 20%, for example, about 10 to 15%;

[0098] The mass percentage of the injection medium is about 60 to 90%, for example, about 75 to 85%.

[0099] In some specific embodiments, the injectable biomedical composite composition of this disclosure comprises PLA short fibers, PLA microspheres, sodium carboxymethyl cellulose, hyaluronic acid, mannitol, and water for injection as generally or specifically defined in this disclosure (page 7 / 12, CN 121473010 A); in more specific embodiments,

[0100] the diameter of the PLA short fibers ranges from about 1 to 50 μm, for example, about 2 to 15 μm, 2 to 10 μm, or 5 to 10 μm, and the length is about 50 to 250 μm or 80 to 250 μm;

[0101] the mass ratio between PLA microspheres and PLA short fibers is about 50:1 to 1:50, for example, about 5:1 to 2:1, for example, about 5:1 to 3:1;

[0102] the mass percentage of PLA short fibers and PLA microspheres is about 2 to 10%, for example, about 2 to 5%;

[0103] the mass percentage of sodium carboxymethyl cellulose is about 2 to 10%. 10%, for example, about 2 to 6%;

[0104] Hyaluronic acid is about 0.5 to 5% by mass, for example, about 0.5 to 3%;

[0105] Mannitol is about 10 to 20% by mass, for example, about 10 to 15%;

[0106] Water for injection is about 60 to 90% by mass, for example, about 75 to 85%.

[0107] The injectable biomedical composite composition of this disclosure can be successfully injected through a 27G needle.

[0108] In a third aspect, this disclosure provides a method for preparing a biomedical composite composition, comprising mixing polyester short fibers with polyester microspheres and optionally one or more pharmaceutical excipients. In a specific embodiment, the polyester short fibers are prepared according to the method of the first aspect of this disclosure.

[0109] In some embodiments, the biomedical composite composition of this disclosure is an injectable formulation, which can be prepared by methods well known to those skilled in the art, for example by uniformly mixing polyester short fibers (preferably polyester short fibers prepared by the methods generally or specifically defined in the first aspect of this disclosure), polyester microspheres, thickeners, filler carriers, buffers, and injection media to obtain a suspension, which is then filled, capped, and packaged to obtain an injectable formulation. The polyester microspheres, thickeners, filler carriers, buffers, and injection media are reagents conventionally used in such formulations in the art, preferably reagents as defined herein.

[0110] In a fourth aspect, this disclosure provides the use of the polyester staple fibers of this disclosure, alone or in combination with other materials, for promoting collagen formation, or alone or in combination with other materials, for promoting collagen formation, or alone or in combination with other materials, in the preparation of biomedical materials for promoting collagen formation.

[0111] This disclosure also provides biomedical composite compositions of this disclosure for promoting collagen formation, or for use in promoting collagen formation, or for use in the preparation of biomedical materials for promoting collagen formation.

[0112] It should be noted that the biomedical composite compositions of this disclosure can be used alone or in combination with other medical repair or cosmetic procedures.

[0113] In a fifth aspect, this disclosure provides the use of the polyester staple fibers of this disclosure, alone or in combination with other materials, in medical aesthetics, or in medical aesthetics; this disclosure also provides the use of the biomedical composite compositions of this disclosure in medical aesthetics, or in medical aesthetics; wherein the medical aesthetics includes, but is not limited to:

[0114] for skin rejuvenation or anti-skin aging, such as improving wrinkles and fine lines, improving skin firmness, improving skin texture and radiance; or for medical aesthetic filling such as soft tissue filling and contour reshaping,

[0115] or for skin repair or regeneration,

[0116] or as a collagen stimulant in combination with other medical aesthetic methods.

[0117] In a sixth aspect, this disclosure also provides the use of the polyester short fibers of this disclosure or the biomedical composite compositions of this disclosure in the preparation of biomedical materials, said biomedical materials being used in medical aesthetics, specifically for skin rejuvenation or anti-skin aging, such as improving wrinkles and fine lines, enhancing skin firmness, improving skin texture and radiance, or for medical aesthetic filling such as soft tissue filling and contouring, or for skin repair or regeneration, or as a collagen stimulant used in combination with other medical aesthetic methods.

[0118] In a seventh aspect, this disclosure provides a method for promoting collagen formation, comprising applying to an individual in need a biomedical composite composition generally or specifically defined in this disclosure.

[0119] In an eighth aspect, this disclosure provides a medical aesthetic method, specifically for skin rejuvenation or anti-skin aging, such as improving wrinkles and fine lines, enhancing skin firmness, improving skin texture and radiance, or for medical aesthetic filling such as soft tissue filling and contour reshaping, or for skin repair or regeneration, comprising applying to an individual in need a biomedical composite composition generally or specifically defined in this disclosure.

[0120] Beneficial Effects

[0121] The polyester short fiber preparation method of this disclosure, by combining spinning technology with cryo-cutting technology, effectively improves the uniformity and preparation efficiency of the fibers, ensures precise control of fiber size, thereby providing a new form of medical aesthetic filling material. In addition, compared with traditional methods, the polyester short fibers disclosed in this invention have significant advantages as medical aesthetic filler materials. They have better biodegradability in vivo and are more conducive to fibroblast adhesion and collagen secretion. Moreover, the use of these short fibers in combination with microspheres can effectively avoid the needle clogging problem that may occur when using pure short fiber materials as fillers, so that the injection of the resulting composite material can be smoothly injected through a 27G needle. At the same time, together with the microspheres, they can enhance the effect of promoting collagen production, thus significantly improving the effect of medical aesthetics.

[0122] The preparation method of this invention has the advantages of controllable operation, mild conditions, and readily available raw materials. It can be conveniently applied to the field of medical aesthetic soft tissue filling and has good market application prospects. Detailed Embodiments

[0123]

[0124] The technical solutions of this invention will be further described in detail below with reference to specific embodiments. It should be understood that the following embodiments are only exemplary illustrations and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technical solutions implemented based on the above content of this invention are covered within the scope of protection intended by this invention.

[0125] Unless otherwise stated, the raw materials and reagents used in the following examples are all commercially available products, or can be prepared by known methods.

[0126] Example: Preparation of polyester staple fiber

[0127] Step S1: High-purity PLA particles (NatureWork 2002D) were added to a laboratory-made melt spinning machine, a suitable heating zone temperature was set, and the particles were fed to a spinneret with a certain aperture. The resulting nascent fibers were cooled and solidified, and collected by high-speed rollers. The fibers were then wound to obtain continuous PLA fibers.

[0128] The continuous PLA fibers obtained in step S1 were measured using a Jeol JSM 7500F scanning electron microscope (accelerating voltage 5.0kV). The results are shown in Figure 1, which shows that the fiber diameter is uniform and the surface is smooth.

[0129] Step S2: Take an appropriate amount of OCT embedding agent to immerse PLA fiber material and freeze-fix it in a low-temperature environment;

[0130] Step S3: Set a certain slice thickness and use a ZD-LQ3300 cryostat (Zhuode Instrument Equipment (Shanghai) Co., Ltd.) to cut the fixed embedding block into short fiber slices of a predetermined thickness;

[0131] Step S4: Wash the short fiber slices with water to remove impurities, centrifuge and collect the precipitate, and dry them to obtain polyester short fiber material.

[0132] Referring to the above general method steps, PLA short fibers of Examples 1 to 4 were prepared according to the conditions shown in the table below: Instruction manual 9 / 12 pages 12 CN 121473010 A

[0133]

[0134] The PLA short fibers obtained in Examples 1-4 were measured with a scanning electron microscope. The results are shown in Figure 2. It shows that the diameter and length of the short fibers in Examples 1 and 2 are uniform, while the short fibers in Examples 3 and 4 are too thin, resulting in uneven length after slicing. In summary, Example 1 was selected for application example preparation.

[0135] Application example: Preparation of injectable solution

[0136] According to the dosage (mass percentage) in the table below, the PLA short fibers obtained in the example, the self-made PLA microspheres (particle size 54.7 ± 7.2 μm, the scanning electron microscope image of which is shown in Figure 3, showing uniform particle size, indicating smoothness) were mixed evenly with sodium carboxymethyl cellulose, hyaluronic acid (molecular weight about 300,000), mannitol and sterile water for injection to obtain a suspension. After filling, capping and packaging, the injectable formulations of Application Examples 1 to 7 were obtained.

[0137]

[0138] An appropriate amount of the injection solution of Application Examples 1, 2 and 3 was taken and observed with a Leica DMLP optical microscope. The photograph is shown in Figure 4. It can be seen that the short fibers and microspheres are evenly mixed and well dispersed in the injection solution.

[0139] Example 1: Injection force test

[0140] For the injection force test, the INSTRON 3400 universal testing machine is used for quantitative detection. It is usually used to evaluate and analyze the injectability of medical aesthetic injection products and can determine the average injection force.

[0141] Specifically, the sample to be tested is taken out from the storage environment and equilibrated in a test environment of 23±2°C for at least 2 hours; the product is drawn out using a 1 mL sterile syringe equipped with a 27G needle, and the syringe is gently flicked vertically upward to remove air bubbles; a small amount of product is ejected to confirm patency; the universal testing machine is turned on and preheated for 30 minutes to perform zero-point calibration and range calibration of the force sensor; the test speed is set to 100 mm / min, the trigger force is 0.05 N, and the data acquisition frequency is 50-200 Hz; the syringe containing the sample is vertically fixed in the fixture with the needle pointing downward, ensuring that the syringe axis is consistent with the probe pushing direction; the push probe is adjusted so that its center is aligned with the piston center to ensure complete vertical contact without tilting; the test program is started, the probe pushes the piston at the set speed, and the force-displacement curve is recorded in real time; the injection stops automatically after reaching the set distance; the average injection force data is extracted from the curve; at least 5 parallel samples are tested repeatedly; finally, the data are statistically analyzed, the average value, standard deviation, and relative standard deviation are calculated, the results are determined to meet the acceptance criteria, and a test report is issued. Instructions for Use, Pages 10 / 12, 13 CN 121473010 A

[0142] The test results are shown in Figure 5. As can be seen from the figure, the injection solution prepared from pure short fibers in Application Example 1 could not be smoothly injected through a 27G needle, while the injection solutions in Application Examples 2 and 3 could be smoothly injected. The injection force meets the requirements of injectable medical aesthetic products.

[0143] Effect Example 2: Cytotoxicity Test

[0144] L929 cells from Wuhan Pronosai Life Science Technology Co., Ltd. were thawed and passaged at least 2-3 times before being used in the experiment. The cultured L929 cells were removed from the culture flask using enzymatic digestive enzymes (trypsin / EDTA). The cell suspension was centrifuged at 200g for 3min and resuspended in DMEM medium containing 10% fetal bovine serum and 1% penicillin-streptomycin. The density was adjusted to 1×105 cells / mL. 100 μL of culture medium was added to the outer wells of a 96-well microtiter plate using a multichannel pipette, and 100 μL of cell suspension at a density of 1 x 10⁵ cells / mL was added to the remaining wells. Cells were incubated for 24 h to form a semi-confluent monolayer. The culture medium was then aspirated, and culture medium containing different concentrations and application examples of the injection solution was added. For the control group, only an equal volume of culture medium was added. After 24 h of incubation, 50 μL of MTT solution was added to each well, and the plate was incubated at 37 °C for another 2 h. The MTT solution was then discarded, and 100 μL of isopropanol solution was added to each well. The plates were shaken, and the absorbance of each well was measured at 570 nm using a Thermo Scientific Multiskan FC microplate reader.Cell viability was calculated according to the following formula:

[0145] Viability (%) =

[0146] Where:

[0147] OD570e——average optical density of 100% extract of test sample;

[0148] OD570b——average optical density of blank.

[0149] The test results are shown in Figure 6. As can be seen from the figure, the injection solutions of each application example at different concentrations did not have cytotoxicity.

[0150] Effect Example 3: Collagen formation staining test

[0151] The injection solution of the application example disclosed in this disclosure (100 μL / mouse) was subcutaneously injected into the sacral region of the back of Balb / c female 6-week-old mice. In application example 1, the needle was blocked during injection, while the injection was successfully completed in application examples 2-7. Twenty-eight days after injection, tissue from the injection area was taken, tissue sections were prepared, and H&E (hematoxylin-eosin staining), Masson and Sirius red staining tests were used to compare and examine the collagen stimulating activity of application examples 2-7.

[0152] For H&E staining, fix the slide for 30s-1min, rinse briefly with water for 1-2s; immerse the slide in a staining jar containing hematoxylin for about 3-5min, then rinse with water for about 5-10s to remove the hematoxylin; then immerse the slide in 1% hydrochloric acid ethanol for 2s, then rinse with water for 1-2s. At this time, the cell nuclei appear purple-blue and the cytoplasm is colorless under the microscope; use a blue-promoting solution (water or 1% ammonia) to restore the blue color for 5-10s, rinse briefly with water for 1-2s, and the cell nuclei appear blue under the microscope; then immerse the slide in a staining jar containing eosin for 30-60s, then rinse the surface clean with water. Under the microscope, the cell nuclei appear blue, and the cytoplasm, muscle fibers, collagen fibers, and erythrocytes appear in varying shades of red.

[0153] For Masson staining, multiple dyes are used for compound staining. It is usually used to observe and analyze collagen fibers in tissues and can distinguish collagen fibers, muscle fibers, and other cell structures. Specifically, the tissue is fixed in Bouin's solution or Zenker's solution, rinsed with running water, and then dehydrated and embedded using standard methods. The sections are dewaxed and returned to the aqueous solution. They are stained with prepared Weigert iron-hematoxylin staining solution for 5-10 minutes. Differentiation is performed using acidic ethanol differentiation solution, followed by rinsing with running water. The sections are then treated with Masson's blue solution for a bluing effect, followed by rinsing with distilled water for 1 minute. Staining is done with Ponceau S and fuchsin for 5-10 minutes. The sections are then rinsed with a weak acid working solution prepared in a 2:1 ratio of distilled water and weak acid for 1 minute. The sections are then rinsed with phosphomolybdic acid solution for 1-2 minutes. Finally, the sections are dehydrated, cleared, and mounted.Instructions 11 / 12 pages 14 CN 121473010 A

[0154] For the Sirius red staining test, it is a more specific staining method that, in addition to showing the total amount of collagen, also distinguishes the main types of collagen. Specifically, the paraffin sections are dewaxed to water: the sections are placed in xylene I for 20 min - xylene II for 20 min - anhydrous ethanol I for 10 min - anhydrous ethanol II for 10 min - 95% alcohol for 5 min - 90% alcohol for 5 min - 80% alcohol for 5 min - 70% alcohol for 5 min - distilled water for washing; then the washed sections are immersed in Sirius red staining solution for 1 h; the sections are directly immersed in pure alcohol for differentiation and dehydration; then placed in xylene I for 5 min - xylene II for 5 min for dehydration and clearing, and mounted with neutral resin.

[0155] The staining results are shown in Figure 7. As can be seen from the figure, the injection solutions of Application Examples 3-7, which contain the short fibers and microspheres of this disclosure, can more effectively stimulate collagen formation compared to the injection solution of Application Example 2, which is prepared from pure microspheres. Among them, the injection solution obtained in Application Example 3 showed the best effect in stimulating collagen formation.

[0156] The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiments. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.Instruction manual, 12 / 12 pages, 15 CN 121473010 A, Figure 1, Figure 2, Figure 3; Instruction manual drawing, 1 / 4 pages, 16 CN 121473010 A, Figure 4, Figure 5; Instruction manual drawing, 2 / 4 pages, 17 CN 121473010 A, Figure 6; Instruction manual drawing, 3 / 4 pages, 18 CN 121473010 A, Figure 7; Instruction manual drawing, 4 / 4 pages, 19 CN 121473010 A, PH 260090 CN202511573530.X PH 260090 Title: POLYESTER STAPLE FIBER-MICROSPHERE COMPOSITE MEDICAL FILLING MATERIAL AS WELL AS PREPARATION METHOD AND APPLICATION THEREOF Abstract: The invention provides a composite composition containing polyester staple fibers and polyester This invention discloses a composite composition comprising polyester staple fibers and polyester microspheres, and its application as a medical aesthetic filler material. The invention also provides a method for preparing the polyester staple fiber. Furthermore, this invention provides a brand-new medical aesthetic filler material solution by utilizing good biocompatibility, biodegradability, and a unique linear structure after the polyester staple fibers and microspheres are compounded.This disclosure utilizes the excellent biocompatibility, biodegradability, and unique linear structure of polyester short fibers combined with microspheres to provide a novel medical aesthetic filler material solution. Abstract.

Claims

1. A method for preparing polyester staple fibers, comprising the following steps: S1. Polyester raw materials are prepared into continuous polyester fiber materials through melt spinning or solution spinning processes; S2. The continuous fiber material obtained in step S1 is frozen and fixed in the presence of an embedding agent; S3. Freeze and slice the material fixed in step S2 to obtain short fiber slices of a certain size; and optionally... S4. Post-process the short fiber slices obtained in step S3.

2. The method of claim 1, wherein step S1 is carried out by melt spinning, wherein the polyester raw material is selected from one or more of polylactic acid (PLA), poly-L-lactide (PLLA), poly(ε-caprolactone) (PCL), polyvalerol (PVL), polyglycolic acid (PGA), polylactic-glycolic acid (PLGA) copolymer, and polyhydroxybutyrate (PHB), and / or heated at a temperature of about 200 to 250°C, and / or spun using a spinneret with an aperture of about 200 to 400 μm, and / or cooled at about 20 to 25°C.

3. The method of claim 1 or 2, wherein the diameter of the polyester continuous fiber material obtained in step S1 is about 1 to 50 μm, for example about 2 to 20 μm.

4. The method of any one of claims 1-3, wherein the embedding agent in step S2 is an OCT embedding agent or an aqueous solution of a blend of PEG and PVA, and / or the freezing conditions are freeze-fixation at about -30 to -20°C for about 0.5 to 1.5 hours.

5. The method of any one of claims 1-4, wherein in step S3, the length of the short fiber slice is about 5 to 300 μm, for example about 80 to 250 μm.

6. The method of any one of claims 1-5, wherein in step S4, the short fiber slices are washed with an aqueous solvent, centrifuged at about 5000-15000 rpm for about 2-10 minutes, and dried for about 20-30 hours.

7. A biomedical composite composition comprising polyester staple fibers and polyester microspheres, and optionally one or more pharmaceutical excipients, wherein the polyester staple fibers have a fiber diameter ranging from about 1 to 50 μm, for example, about 2 to 20 μm, and a length ranging from about 5 to 300 μm; preferably, the polyester staple fibers have a fiber diameter ranging from about 2 to 15 μm, 2 to 10 μm, or 5 to 10 μm, and a length ranging from about 50 to 250 μm or 80 to 250 μm.

8. The biomedical composite composition of claim 7, wherein the polyester staple fiber is a polyester staple fiber prepared by the method according to any one of claims 1 to 6.

9. The biomedical composite composition of claim 7 or 8, wherein the polyester microspheres are selected from one or more of PLA microspheres, PCL microspheres, PLGA microspheres, and PGA microspheres, preferably PLA microspheres, and / or the polyester microspheres have a diameter of about 1 to 200 μm, for example about 20 to 60 μm.

10. The biomedical composite composition of any one of claims 7-9, wherein the mass ratio of the polyester microspheres to the polyester short fibers is about 50:1 to 1:50, for example about 5:1 to 2:1, for example about 5:1 to 3:

1.

11. The biomedical composite composition according to any one of claims 7-10, wherein the total content of the polyester short fibers and polyester microspheres is about 2-30%, preferably about 2-5%.

12. The biomedical composite composition of any one of claims 7-11, which is in the form of an injection solution, further comprising a thickener, a filler carrier, a buffer, and an injection medium; preferably further comprising sodium carboxymethyl cellulose, hyaluronic acid, mannitol, and water for injection.

13. The biomedical composite composition according to any one of claims 7-12, wherein... PLA short fibers have diameters ranging from approximately 2 to 15 μm, 2 to 10 μm, or 5 to 10 μm, and lengths ranging from approximately 50 to 250 μm or 80 to 250 μm. The mass ratio of PLA microspheres to PLA short fibers is approximately 5:1 to 2:1, preferably approximately 5:1 to 3:1; The mass percentage of PLA microspheres and PLA short fibers is about 2 to 10%, preferably about 2 to 5%; The sodium carboxymethyl cellulose is present in a mass percentage of about 2 to 10%, preferably about 2 to 6%; The mass percentage of hyaluronic acid is approximately 0.5% to 5%, preferably approximately 0.5% to 3%. The mass percentage of mannitol is about 10 to 20%, preferably about 10 to 15%; The mass percentage of water for injection is approximately 60-90%, preferably approximately 75-85%.

14. The polyester short fibers prepared according to any one of claims 1-6 may be used alone or in combination with other materials for medical aesthetic purposes, such as for promoting collagen formation, for example for skin rejuvenation or anti-skin aging, such as improving wrinkles and fine lines, improving skin firmness, improving skin texture and radiance, or for medical aesthetic filling such as soft tissue filling and contouring, or for skin repair or regeneration, or as a collagen stimulant in combination with other medical aesthetic procedures.

15. The use of the biomedical composite composition of any one of claims 7-13 in medical aesthetics, for example, for promoting collagen formation, for example, for skin rejuvenation or anti-skin aging such as improving wrinkles and fine lines, improving skin firmness, improving skin texture and radiance, or for medical aesthetic filling such as soft tissue filling and contouring, or for skin repair or regeneration, or as a collagen stimulant used in combination with other medical aesthetic procedures.

16. Use of the polyester staple fiber prepared according to any one of claims 1-6 or the biomedical composite composition according to any one of claims 7-13 in the preparation of biomedical materials for medical aesthetics, for example, for promoting collagen production, specifically for skin rejuvenation or anti-skin aging such as improving wrinkles and fine lines, improving skin firmness, improving skin texture and radiance, or for medical aesthetic filling such as soft tissue filling and contouring, or for skin repair or regeneration, or as a collagen stimulant used in combination with other medical aesthetic procedures.

17. A method for promoting collagen formation, comprising administering to an individual in need the biomedical composite composition of any one of claims 7-13.

18. A medical aesthetic method, specifically a skin rejuvenation or anti-skin aging method such as improving wrinkles and fine lines, enhancing skin firmness, improving skin texture and radiance, or a medical aesthetic filling method such as soft tissue filling and contouring, or a skin repair or regeneration method, comprising applying the biomedical composite composition of any one of claims 7-13 to an individual in need.

Images