Soft tissue filling preparation containing calcium oxalate particles as well as preparation method and application of soft tissue filling preparation

Abstract

The invention relates to the technical field of biological materials, in particular to a soft tissue filling preparation containing calcium oxalate particles, which comprises calcium oxalate particles and a gel composite solution, the gel composite solution contains cross-linked and / or non-cross-linked gel dry powder; the mass ratio of the calcium oxalate particles in the soft tissue filling preparation is 5-50%. The preparation method comprises the following steps: selecting calcium oxalate particles with proper particle size; preparing a gel composite solution; adding calcium oxalate particles into the gel composite solution; and filling the product into a pre-filled syringe or penicillin bottle to obtain the soft tissue filling preparation containing the calcium oxalate particles. The soft tissue filling preparation can be applied to skin filling and in-vivo implantation. The soft tissue filling preparation is long in stimulation maintaining time and high in biodegradation safety, and can be used for soft tissue filling so as to reduce skin wrinkles and depressions at injection positions.

Description

Technical Field

[0001] The invention relates to the technical field of biomaterials, and in particular to a soft tissue filling preparation containing calcium oxalate particles, a preparation method and application thereof. Background Art

[0002] Facial injection of soft tissue filling preparations can effectively improve the patient's facial tissue volume loss, contour changes and static wrinkles, and is one of the important means to achieve soft tissue rejuvenation in a non-surgical way. Traditional filling materials are mainly based on hyaluronic acid and collagen, which are the same or similar components of the human extracellular matrix. Although they can be maintained for a longer period of time (3 to 12 months) through cross-linking technology, with the improvement of medical aesthetics awareness and the upgrading of consumer demand, traditional hyaluronic acid and other space-occupying filling preparations obviously can no longer meet consumers' demand for high-quality medical aesthetics. Medical aesthetic regeneration injections have become the new favorite in the injection medical aesthetics market with their advantages such as more natural and realistic treatment effects and higher safety.

[0003] The mechanism of action of regenerative injectable fillers in the process of soft tissue filling relies on the body's foreign body reaction to the injected material, activating the activity of fibroblasts in the skin, thereby inducing the regeneration of collagen and elastic fibers, improving skin density, and is used to fill depressions, tighten the skin, and reduce wrinkles. It should be noted that its active regeneration mechanism is different from the pathological inflammatory hyperplasia reaction. The regenerated tissue not only looks smooth and symmetrical in appearance, but also has similar functions to healthy physiological tissue, thus achieving a natural soft tissue rejuvenation effect.

[0004] Unlike synthetic organic polymers such as polylactic acid (PLA), polycaprolactone (PCL), polymethyl methacrylate (PMMA), polyvinyl alcohol (PVA) and other materials, inorganic materials can also stimulate collagen regeneration in the body, and the incidence of adverse reactions such as nodules and macules caused by injection is low. Calcium oxalate, as a widely existing biomineral in nature, mostly comes from food and physiological crystals formed by normal metabolism of the body, so its biological safety as a filling material is unquestionable. In addition, calcium oxalate particles have excellent mechanical support properties. While stimulating regeneration, they can also play a role in instantly filling skin depressions, thereby achieving beautification and improvement of skin appearance. The size of calcium oxalate particles in filling preparations will directly affect its stimulating effect on collagen regeneration. If it is smaller than the diameter of macrophages (14-20μm), it will be phagocytosed by cells and further cleaned up, weakening the regeneration and filling effects. On the contrary, if the particle diameter is too large, it may cause excessive stimulation and induce adverse reactions such as inflammatory hyperplasia. For example, Chinese patent CN119033752A discloses the use of a gallic acid derivative in inhibiting the growth of calcium oxalate monohydrate crystals, which inhibits the growth of calcium oxalate monohydrate crystals, reduces aggregation / adhesion, reduces crystal deposition in the body and damage to cells caused by excessive inflammatory response.

[0005] Therefore, the present invention aims to develop a soft tissue filling preparation containing calcium oxalate particles, which triggers fibroblasts to synthesize collagen and elastin fiber networks in the tissue, and as the implant is gradually degraded in the body, the filling and coverage of the regenerated tissue is achieved. Summary of the invention

[0006] The technical problem to be solved by the present invention is: to overcome the shortcomings of the prior art, to provide a soft tissue filling preparation containing calcium oxalate particles, a preparation method and its application, to solve the current safety hazards caused by the easy agglomeration of inorganic particles and poor self-stability, and to fill the technical problem of calcium oxalate as a facial soft tissue filler.

[0007] The technical solution adopted by the present invention to solve its technical problem is:

[0008] First aspect:

[0009] Provided is a soft tissue filling preparation containing calcium oxalate particles, comprising

[0010] Calcium oxalate granules and gel composite solution;

[0011] The gel composite solution contains cross-linked and / or non-cross-linked gel dry powder;

[0012] The mass ratio of the calcium oxalate particles in the soft tissue filling preparation is 5 to 50%.

[0013] Furthermore, the calcium oxalate particles are calcium oxalate monohydrate, and the average particle size is 20 to 40 μm.

[0014] Furthermore, the content of the cross-linked gel powder in the gel composite solution is 10-30 mg / mL, and the content of the non-cross-linked gel powder is 0-15 mg / mL.

[0015] Further, the cross-linked gel includes: one or more of sodium hyaluronate gel, collagen gel, silk fibroin gel, and agarose gel;

[0016] The non-cross-linked gel includes any one or more of hyaluronic acid and its sodium salt, cellulose derivatives, sodium alginate, dextran, and chitosan.

[0017] Furthermore, the gel composite solution also contains nutrients and anesthetic substances;

[0018] The nutrients include: one or more of amino acids, polypeptides, proteins, polysaccharides, polyols, vitamins, and nucleotides;

[0019] The anesthetic substance includes any one of lidocaine hydrochloride, procaine hydrochloride and tetracaine hydrochloride.

[0020] Furthermore, the nutrient has an amino acid content of 0 to 5 mg / mL, a polypeptide content of 0 to 10 mg / mL, a vitamin content of 0 to 60 μg / mL, and a nucleotide content of 0 to 10 mg / mL;

[0021] The content of local anesthetic in the anesthetic substance is 0 to 10 mg / mL.

[0022] Furthermore, the system pH of the soft tissue filling preparation is 6.5 to 8.5, and the osmotic pressure is 200 to 400 mOsmol / kg.

[0023] Second aspect:

[0024] A method for preparing the soft tissue filling preparation containing calcium oxalate particles is provided, comprising the following steps:

[0025] Step S1: selecting calcium oxalate particles of appropriate particle size;

[0026] Step S2: fully dissolving the gel dry powder, local anesthetic and nutrients in the aqueous phase system to prepare a gel composite solution;

[0027] Step S3: adding calcium oxalate particles into the gel composite solution prepared in step S2 according to a certain mass ratio, and repeatedly blending until uniform dispersion;

[0028] Step S4: Fill the product in step S3 into a prefilled syringe or vial to obtain a soft tissue filling preparation containing calcium oxalate particles.

[0029] The third aspect:

[0030] Provided is a use of the soft tissue filling preparation containing calcium oxalate particles in the field of skin filling and in vivo implantation.

[0031] The beneficial effects of the present invention are:

[0032] The soft tissue filling preparation containing calcium oxalate particles of the present invention creatively disperses the calcium oxalate particles evenly inside the gel, and the crystal form of the calcium oxalate particles is structurally stable calcium oxalate monohydrate. Because of its natural composition and high biosafety, it reduces the immune rejection reaction caused by the source of raw materials of injectable products. In addition, the mechanical supporting properties of the calcium oxalate particles can play a role in instantly filling skin depressions while stimulating collagen regeneration.

[0033] The calcium oxalate particle-containing filling preparation of the present invention has a long-lasting stimulation and high biodegradation safety, and can be used for soft tissue filling to reduce skin wrinkles and depressions at the injection site.

[0034] A variety of fill formulation types are available to maintain product safety and efficacy.

[0035] The calcium oxalate particles used in the present invention are natural and highly biocompatible, thus reducing the immune rejection reaction caused by the raw material source of injection products.

[0036] The soft tissue filling preparation containing calcium oxalate particles prepared by the present invention has good mechanical support performance and can play an immediate filling role while stimulating collagen regeneration.

[0037] The soft tissue filling preparation containing calcium oxalate particles prepared by the present invention is added with a variety of functional ingredients, which can improve the injection comfort and wrinkle repair satisfaction. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] The present invention is further described below in conjunction with the accompanying drawings.

[0039] Figure 1 This is a microscopic morphology of the calcium oxalate particle-filled preparation prepared in Example 1, with a scale of 50 μm;

[0040] Figure 2 This is a microscopic morphology of the calcium oxalate particle-filled preparation prepared in Example 2 after wet heat sterilization, with a scale of 50 μm;

[0041] Figure 3 This is a microscopic morphology of the calcium oxalate particle-filled preparation prepared in Comparative Example 2, with a scale bar of 50 μm;

[0042] Figure 4 This is a physical picture of the calcium oxalate granular filling preparation product prepared in Example 3;

[0043] Figure 5 This is a particle size distribution diagram of calcium oxalate particles in the calcium oxalate particle filling preparation prepared in Example 3;

[0044] Figure 6 The filling effect of the calcium oxalate particle filling preparation prepared in Example 3 on mice after subcutaneous injection, the left side was not injected, and the right side was injected with 0.1 mL of the filling preparation;

[0045] Figure 7 This is the Masson staining result of the calcium oxalate particle filling preparation prepared in Example 3 implanted subcutaneously in mice for 2 weeks, with a scale bar of 50 μm;

[0046] Figure 8 This is a Western Blot staining result of the calcium oxalate particle filling preparation prepared in Example 3 implanted subcutaneously in mice for 2 weeks;

[0047] Fig. 9 This is the Masson staining result of the calcium oxalate particle filling preparation prepared in Example 3 implanted subcutaneously in mice at 1M. The scale bar is 50 μm.

[0048] Fig.10 This is the H&E staining result of the calcium oxalate particle filling preparation prepared in Example 3 implanted subcutaneously in mice 1M, with a scale bar of 50 μm. DETAILED DESCRIPTION

[0049] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution of the present invention will be clearly and completely described below in conjunction with the accompanying drawings. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0050] Some embodiments of the present invention are described in detail below in conjunction with the accompanying drawings. In the absence of conflict, the following embodiments and features in the embodiments can be combined with each other.

[0051] This embodiment discloses a soft tissue filling preparation containing calcium oxalate particles, comprising

[0052] Calcium oxalate granules and gel composite solution;

[0053] The gel composite solution contains cross-linked and / or non-cross-linked gel dry powder;

[0054] The mass ratio of the calcium oxalate particles in the soft tissue filling preparation is 5 to 50%.

[0055] In some embodiments, specifically, the calcium oxalate particles are calcium oxalate monohydrate, and the average particle size is 20 to 40 μm.

[0056] The calcium oxalate particles are in the shape of rhombus polyhedrons and have multiple surfaces, which increase the contact area with cells, improve cell adhesion and retention time, and can stimulate and accelerate collagen regeneration.

[0057] In some embodiments, specifically, the content of the cross-linked gel dry powder in the gel composite solution is 10-30 mg / mL, and the content of the non-cross-linked gel dry powder is 0-15 mg / mL.

[0058] In some embodiments, specifically, the cross-linked gel includes: one or more of sodium hyaluronate gel, collagen gel, silk fibroin gel, and agarose gel;

[0059] The non-cross-linked gel includes any one or more of hyaluronic acid and its sodium salt, cellulose derivatives, sodium alginate, dextran, and chitosan.

[0060] In some embodiments, specifically, the gel composite solution further contains nutrients and anesthetic substances;

[0061] The nutrients include: one or more of amino acids, polypeptides, proteins, polysaccharides, polyols, vitamins, and nucleotides;

[0062] The anesthetic substance includes any one of lidocaine hydrochloride, procaine hydrochloride and tetracaine hydrochloride.

[0063] In some embodiments, specifically, the nutrient has an amino acid content of 0 to 5 mg / mL, a polypeptide content of 0 to 10 mg / mL, a vitamin content of 0 to 60 μg / mL, and a nucleotide content of 0 to 10 mg / mL;

[0064] The content of local anesthetic in the anesthetic substance is 0 to 10 mg / mL.

[0065] In some embodiments, specifically, the system pH of the soft tissue filling preparation is 6.5-8.5, and the osmotic pressure is 200-400 mOsmol / kg.

[0066] The present disclosure also provides a method for preparing the soft tissue filling preparation containing calcium oxalate particles, comprising the following steps:

[0067] Step S1: selecting calcium oxalate particles of appropriate particle size;

[0068] Step S2: fully dissolving the gel dry powder, local anesthetic and nutrients in the aqueous phase system to prepare a gel composite solution;

[0069] Step S3: adding calcium oxalate particles into the gel composite solution prepared in step S2 according to a certain mass ratio, and repeatedly blending until uniform dispersion;

[0070] Step S4: Fill the product in step S3 into a prefilled syringe or vial to obtain a soft tissue filling preparation containing calcium oxalate particles.

[0071] The disclosed embodiments also provide an application of the soft tissue filling preparation containing calcium oxalate particles in the field of skin filling and in vivo implantation.

[0072] The present invention is described below through several embodiments: It should be noted that the description order of the following embodiments is not intended to limit the preferred order of the embodiments of the present application. In the following embodiments, the description of each embodiment has its own emphasis. For parts that are not described in detail in a certain embodiment, please refer to the relevant description of other embodiments.

[0073] Example 1

[0074] A method for preparing a soft tissue filling preparation containing calcium oxalate particles comprises the following steps:

[0075] S1: Prepare calcium oxalate particles according to the previous research method, and collect calcium oxalate monohydrate crystals with an average particle size of about 20 μm;

[0076] S2: Weigh 100 mg of 200 wDa sodium hyaluronate, 20 mg of L-carnosine and 30 mg of lidocaine hydrochloride and add them into 10 mL of water for injection and fully dissolve them to prepare a gel composite solution;

[0077] S3: adding calcium oxalate particles at a mass ratio of 5% to the above gel composite solution, repeatedly blending until uniformly dispersed, and adjusting the system pH to about 6.5 and the osmotic pressure to about 200 mOsm / kg;

[0078] S4: Fill the gel composite solution containing calcium oxalate particles into a prefilled syringe. The preparation process is aseptic production to prepare an injectable soft tissue filling preparation containing calcium oxalate particles. The storage temperature is 4°C.

[0079] Example 2

[0080] A method for preparing a soft tissue filling preparation containing calcium oxalate particles comprises the following steps:

[0081] S1: Prepare calcium oxalate particles according to the previous research method, and collect calcium oxalate monohydrate crystals with an average particle size of about 20 μm;

[0082] S: Weigh 10 mg of 200 wDa molecular weight sodium hyaluronate, 90 mg of cross-linked sodium hyaluronate gel powder, 10 mg of L-carnosine, 0.3 mg of vitamin B2 and 5 mg of glycine, add them into 5 mL of phosphate buffer and fully dissolve them to prepare a gel composite solution;

[0083] S3: adding calcium oxalate particles at a mass ratio of 5% to the above gel composite solution, repeatedly blending until uniformly dispersed, and adjusting the system pH to about 7.0 and the osmotic pressure to about 350mOsm / kg;

[0084] S4: Fill the gel composite solution containing calcium oxalate particles into a prefilled syringe, and use moist heat sterilization to prepare an injectable soft tissue filling preparation containing calcium oxalate particles. The storage temperature is 25°C.

[0085] like Figure 2 As shown, the microscopic morphology of the calcium oxalate particle filling preparation prepared by this example.

[0086] Example 3

[0087] A method for preparing a soft tissue filling preparation containing calcium oxalate particles comprises the following steps:

[0088] S1: Prepare calcium oxalate particles according to the previous research method, and collect calcium oxalate monohydrate crystals with an average particle size of about 40 μm;

[0089] S: Weigh 50 mg of 200 wDa molecular weight sodium hyaluronate, 150 mg of carboxymethyl cellulose, 20 mg of alanine and 20 mg of glycine and add them to 10 mL of normal saline to fully dissolve to prepare a gel composite solution;

[0090] S3: adding calcium oxalate particles at a mass ratio of 30% to the above gel composite solution, repeatedly blending until uniformly dispersed, and adjusting the system pH to about 8.0 and the osmotic pressure to about 300 mOsm / kg;

[0091] S4: Fill the gel composite solution containing calcium oxalate particles into a prefilled syringe. The preparation process is aseptic production to prepare an injectable soft tissue filling preparation containing calcium oxalate particles. The storage temperature is 8°C.

[0092] Example 4

[0093] A method for preparing a soft tissue filling preparation containing calcium oxalate particles comprises the following steps:

[0094] S1: Prepare calcium oxalate particles according to the previous research method, and collect calcium oxalate monohydrate crystals with an average particle size of about 30 μm;

[0095] S: Weigh 250 mg of cross-linked sodium hyaluronate dry powder, 20 mg of alanine, 0.5 mg of vitamin B2 and 20 mg of procaine hydrochloride and add them to 10 mL of normal saline to fully dissolve to prepare a gel composite solution;

[0096] S3: adding calcium oxalate particles at a mass ratio of 50% to the above gel composite solution, repeatedly blending until uniformly dispersed, and adjusting the system pH to about 8.5 and the osmotic pressure to about 400 mOsm / kg;

[0097] S4: Fill the gel composite solution containing calcium oxalate particles into a prefilled syringe, and use moist heat sterilization to prepare an injectable filling preparation containing calcium oxalate particles. The storage temperature is 15°C.

[0098] Example 5

[0099] A method for preparing a soft tissue filling preparation containing calcium oxalate particles comprises the following steps:

[0100] S1: Prepare calcium oxalate particles according to the previous research method, and collect calcium oxalate monohydrate crystals with an average particle size of about 20 μm;

[0101] S: Weigh 200 mg collagen, 1.2 mg vitamin B2, 10 mg nucleotide and 40 mg lidocaine hydrochloride and add them into 20 mL water for injection and fully dissolve them to prepare a gel composite solution;

[0102] S3: adding calcium oxalate particles at a mass ratio of 20% to the above gel composite solution, repeatedly blending until uniformly dispersed, and adjusting the system pH to about 6.5 and the osmotic pressure to about 300 mOsm / kg;

[0103] S4: Fill the gel composite solution containing calcium oxalate particles into a vial, use freeze-drying technology to prepare the lyophilized powder preparation, and prepare the calcium oxalate particle filling preparation for injection by irradiation sterilization. The storage temperature is 4°C.

[0104] Comparative Example 1

[0105] A method for preparing a soft tissue filling preparation containing calcium oxalate particles comprises the following steps:

[0106] S1: Prepare calcium oxalate particles according to the previous research method, and collect calcium oxalate monohydrate crystals with an average particle size of about 10 μm;

[0107] S: Weigh 100 mg of 120 wDa sodium hyaluronate, 20 mg of L-carnosine and 30 mg of lidocaine hydrochloride and add them into 10 mL of water for injection and fully dissolve them to prepare a gel composite solution;

[0108] S3: adding calcium oxalate particles at a mass ratio of 5% to the above gel composite solution, repeatedly blending until uniformly dispersed, and adjusting the system pH to about 7.5 and the osmotic pressure to about 400 mOsm / kg;

[0109] S4: Filling the gel composite solution containing calcium oxalate particles into a prefilled syringe. The preparation process is aseptic production. Prepare an injectable filling preparation containing calcium oxalate particles. The storage temperature is 25°C.

[0110] Comparative Example 2

[0111] A method for preparing a soft tissue filling preparation containing calcium oxalate particles comprises the following steps:

[0112] S1: Calcium oxalate particles were prepared according to the previous research method, and monohydrate calcium oxalate crystals with an average particle size of about 40 μm were collected, and anhydrous calcium oxalate particles were obtained by high-temperature dry baking at 250°C for 60 minutes;

[0113] S2: Weigh 150 mg of cross-linked sodium hyaluronate dry powder, 20 mg of alanine, and 0.5 mg of vitamin B2 and add them into 10 mL of normal saline to fully dissolve to prepare a gel composite solution;

[0114] S3: adding calcium oxalate particles at a mass ratio of 40% to the above gel composite solution, repeatedly blending until uniformly dispersed, and adjusting the system pH to about 7.0 and the osmotic pressure to about 350mOsm / kg;

[0115] S4: Fill the gel composite solution containing calcium oxalate particles into a prefilled syringe, and use moist heat sterilization to prepare an injectable filling preparation containing calcium oxalate particles. The storage temperature is 8°C.

[0116] like Figure 1 As shown in the figure, the internal microscopic diagram of the filling preparation containing calcium oxalate particles shows that there is no obvious adhesion / aggregation between the calcium oxalate particles, showing good uniform dispersion. In addition, the gel product containing calcium oxalate particles for injection is sterilized by high-temperature steam;

[0117] like Figure 2 As shown, the morphology of the internal calcium oxalate particles has not changed or broken. On the contrary, in the comparative example 2, anhydrous calcium oxalate particles are used. Figure 3 There are no calcium oxalate particles with obvious morphology inside the injection product shown, which proves that the monohydrate compound of calcium oxalate crystal has the best structural stability and can maintain the original rhombus polyhedron morphology to increase the contact area with cells and improve cell adhesion and retention time.

[0118] The actual product picture of the injection filling preparation prepared in Example 3 and the particle size distribution diagram of the calcium oxalate particles inside are as follows: Figure 4 , 5As shown in FIG. 1 , the microparticle-filled preparation product is a milky white gel. Figure 6 As shown in the figure, the calcium oxalate particle-filled preparation for injection prepared in Example 3 was implanted into the subcutaneous tissue layer of mice. The color of the filling preparation was similar to that of the normal dermis, which could effectively prevent the occurrence of the Tyndall phenomenon and had obvious tissue volume filling and non-displacement effects. In addition, the expression of regenerated collagen after the calcium oxalate particle-filled preparation was implanted into the subcutaneous tissue for 2 weeks was shown in the figure. Figure 7 and 8 As shown in the figure, the implanted calcium oxalate particles induce a foreign body inflammatory response in the tissue without clinical symptoms. The calcium oxalate particles are surrounded by fibroblasts and newly generated collagen, which then causes collagen fibers to entangle around the particles, followed by the fibrous tissue proliferation stage, and finally the generation of type I collagen in the extracellular matrix. Figure 8 As shown in the figure, the collagen content of subcutaneous tissue regeneration 2 weeks after implantation, the filling preparation containing calcium oxalate particles induced an increase in the level of collagen regeneration over time. Fig. 9 As shown in Figure 2, a well-woven collagen fiber network gradually formed, which was similar to the natural skin tissue structure. In addition, the H&E staining results were as follows: Fig.10 As shown, increased vascular expression in the tissue surrounding the implanted material helps improve blood circulation, providing nutrients and energy for the regenerated tissue and timely discharge of cellular metabolic waste.

[0119] In summary, the present invention provides a soft tissue filling preparation containing calcium oxalate particles, creatively introduces structurally stable calcium oxalate monohydrate crystalline particles as tissue regeneration materials, and timely fills the vacancy in the field of calcium oxalate as a soft tissue filling material.

[0120] The various devices selected in this application (components whose specific structures are not described) are all universal standard parts or components known to technical personnel in this field, and their structures and principles can be known to technical personnel through technical manuals or through conventional experimental methods.

[0121] In the description of the embodiments of the present invention, unless otherwise clearly specified and limited, the terms "installed", "connected", and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, or it can be the internal communication of two components. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0122] In the description of the present invention, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc., indicating the orientation or positional relationship, are based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as limiting the present invention. In addition, the terms "first", "second", and "third" are used for descriptive purposes only, and cannot be understood as indicating or implying relative importance.

[0123] In the several embodiments provided in the present application, it should be understood that the disclosed systems, devices and methods can be implemented in other ways. The device embodiments described above are merely schematic. For example, the division of the units is only a logical function division. There may be other division methods in actual implementation. For example, multiple units or components can be combined or integrated into another system, or some features can be ignored or not executed. Another point is that the mutual coupling or direct coupling or communication connection shown or discussed can be through some communication interfaces, and the indirect coupling or communication connection of devices or units can be electrical, mechanical or other forms.

[0124] The units described as separate components may or may not be physically separated, and the components shown as units may or may not be physical units, that is, they may be located in one place or distributed on multiple network units. Some or all of the units may be selected according to actual needs to achieve the purpose of the solution of this embodiment.

[0125] In addition, each functional unit in each embodiment of the present invention may be integrated into one processing unit, or each unit may exist physically separately, or two or more units may be integrated into one unit.

[0126] Based on the above ideal embodiments of the present invention, the relevant staff can make various changes and modifications without departing from the technical concept of the present invention through the above description. The technical scope of the present invention is not limited to the contents of the specification, and its technical scope must be determined according to the scope of the claims.

Claims

1. A soft tissue filling preparation containing calcium oxalate particles, characterized in that: include Calcium oxalate granules and gel composite solution; The gel composite solution contains cross-linked and / or non-cross-linked gel dry powder; The mass ratio of the calcium oxalate particles in the soft tissue filling preparation is 5 to 50%.

2. The soft tissue filling preparation containing calcium oxalate particles according to claim 1, characterized in that: The calcium oxalate particles are calcium oxalate monohydrate, and the average particle size is 20 to 40 μm.

3. The soft tissue filling preparation containing calcium oxalate particles according to claim 1, characterized in that: The content of cross-linked gel dry powder in the gel composite solution is 10-30 mg / mL, and the content of non-cross-linked gel dry powder is 0-15 mg / mL.

4. The soft tissue filling preparation containing calcium oxalate particles according to claim 3, characterized in that: The cross-linked gel includes: one or more of sodium hyaluronate gel, collagen gel, silk fibroin gel, and agarose gel; The non-cross-linked gel includes any one or more of hyaluronic acid and its sodium salt, cellulose derivatives, sodium alginate, dextran, and chitosan.

5. The soft tissue filling preparation containing calcium oxalate particles according to claim 3, characterized in that: The gel composite solution also contains nutrients and anesthetic substances; The nutrients include: one or more of amino acids, polypeptides, proteins, polysaccharides, polyols, vitamins, and nucleotides; The anesthetic substance includes any one of lidocaine hydrochloride, procaine hydrochloride and tetracaine hydrochloride.

6. The soft tissue filling preparation containing calcium oxalate particles according to claim 5, characterized in that: The nutrient has an amino acid content of 0 to 5 mg / mL, a polypeptide content of 0 to 10 mg / mL, a vitamin content of 0 to 60 μg / mL, and a nucleotide content of 0 to 10 mg / mL; The content of local anesthetic in the anesthetic substance is 0 to 10 mg / mL.

7. The soft tissue filling preparation containing calcium oxalate particles according to claim 1, characterized in that: The system pH of the soft tissue filling preparation is 6.5 to 8.5, and the osmotic pressure is 200 to 400 mOsmol / kg.

8. A method for preparing a soft tissue filling preparation containing calcium oxalate particles according to any one of claims 1 to 7, comprising the following steps: Step S1: selecting calcium oxalate particles of appropriate particle size; Step S2: fully dissolving the gel dry powder, local anesthetic and nutrients in the aqueous phase system to prepare a gel composite solution; Step S3: adding calcium oxalate particles into the gel composite solution prepared in step S2 according to a certain mass ratio, and repeatedly blending until uniform dispersion; Step S4: Fill the product in step S3 into a prefilled syringe or vial to obtain a soft tissue filling preparation containing calcium oxalate particles.

9. Use of the soft tissue filling preparation containing calcium oxalate particles according to any one of claims 1 to 7 in the field of skin filling and in vivo implantation.

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