Complex, manufacturing method for the complex, and filling composition for aesthetic surgical procedures using the complex

Abstract

The present invention relates to a formulation, a process for preparing the formulation, and a filling composition for plastic surgery using the formulation. The formulation includes biodegradable particles and a water-soluble polymer. The biodegradable particles each have a network structure in the particles. Since the formulation is formulated in a cake shape, it can have excellent storage stability and dispersibility over a long period of time.

Description

Technical Field

[0001] (Technical Field) The present invention relates to a formulation (or composite) comprising two or more components (or components), a process (or step or method) for preparing (or manufacturing or forming) the formulation, and a filling composition (or filler composition or filler composition) for plastic surgery (or plastic surgery or plastic surgery) using the formulation (for example, a filling composition (or filler composition or filler composition) for dermatoplasty (or skin plastic surgery or skin plastic surgery)).

Background Art

[0002] (Background Art) Plastic surgery (or plastic surgery or plastic surgery) is being performed. In plastic surgery, a filling composition (or filler composition or filler composition) is injected (or injection) subcutaneously or into tissue. The purpose is, for example, to correct (or improve or modify) human body functions or for aesthetic (or cosmetic) purposes. Such a filling composition is preferably safe for the human body, biocompatible (or biocompatible), and biodegradable (or biodegradable).

[0003] Such a filling composition comprises a natural polymer (for example, collagen, gelatin, hyaluronic acid and dextran) or a synthetic polymer (for example, polylactic acid, polyglutamic acid, polycaprolactone and polyacrylamide).

[0004] However, natural polymers or synthetic polymers begin to decompose after a certain period of time has elapsed, so the shelf life (or shelf life) of a filling composition (or filler composition or filler composition) containing such a polymer is limited. Furthermore, most of the filling compositions are administered using a syringe. In such cases (or situations or events), when the viscosity (or viscosity) of the filling composition is very high or the dispersibility (or dispersibility) is poor, it may be difficult to inject (or inject) such a filling composition using a thin needle (or needle). And the force (or force) applied (or imparted) to the syringe (injection force (or injection force or injection force)) inevitably increases, giving discomfort and fatigue to the practitioner (or operator or operator).

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0006] (Problems of the Technology) An object of the present invention is to provide a formulation (or composite) and a process (or step or method) for preparing (or manufacturing or forming) the formulation. The formulation has excellent long-term storage (or storage) and dispersibility (or dispersibility), which can improve the use environment (or operating environment or surgical environment) of a filling composition (or filler composition or filler composition) for plastic surgery (or plastic surgery or plastic surgery).

[0007] Furthermore, an object of the present invention is to provide a filling composition (or filler composition or filler composition) for plastic surgery (or plastic surgery or plastic surgery), and such plastic surgery can be performed relatively easily.

Means for Solving the Problem

[0008] (Solution to the Problem (or Solving Method)) According to an embodiment of the present invention, in order to achieve the above object, there is provided a formulation (or composite) containing biodegradable particles (or biodegradable particles or biodegradable particles) and a water-soluble polymer (or water-soluble polymer or water-soluble polymer), which is a cake-like formulation (or preparation) (or has a cake-like formulation or cake formulation). Each of the biodegradable particles has a network structure (or network structure or network structure) in the particles.

[0009] According to another embodiment of the present invention, there is provided a process (or step or method) for preparing (or manufacturing or forming) a formulation (or composite). The process includes the following steps (1) to (6). (1) A step of dissolving a biodegradable raw material (or raw material) in a first solvent (or first solvent) to prepare a biodegradable solution (or biodegradable solution or biodegradable solution). (2) A step of spraying (or spraying) the biodegradable solution into a second solvent (or second solvent) to form biodegradable particles (or biodegradable particles or biodegradable particles), wherein each of the biodegradable particles has a network structure (or network structure or network structure) in the particles, and the second solvent has a lower freezing point (or freezing point or freezing point or freezing point) than the first solvent. (3) A step of sorting (or sorting or sorting) the biodegradable particles by size (or size or dimension). (4) To prepare a mixed solution (or mix solution), a step of adding biodegradable particles sorted by the size to a solution of a water-soluble polymer (or water-soluble polymer solution). (5) A step of filling the mixed solution into a container (or container), and (6) A step of freeze-drying (or freeze-dry) the mixed solution filled in the container to form a formulation (or composite), wherein the formulation is formulated (or compounded) into a cake shape (or has a cake-shaped formulation (or compound) or cake formulation), the step

[0010] According to another embodiment of the present invention, a filling composition (or filler composition or filler composite) for plastic surgery (or plastic surgery or plastic surgery) is provided. In the filling composition, the above-mentioned formulation (or composite) is dispersed.

Advantages of the Invention

[0011] (Advantageous effects of the invention) The formulation (or composite) according to the present invention contains biodegradable particles, and each of the biodegradable particles has a network structure (or network structure or network structure) in the particles. Since the formulation (or composite) is formulated (or compounded) into a cake shape (or has a cake-shaped formulation (or compound) or cake formulation) and has a fluffy texture (or fluffy feel or fluffy touch or fluffy texture), it can be rapidly dispersed in a solvent and can be uniformly dispersed. Furthermore, since the formulation (or composite) according to the present invention is formulated (or compounded) in a cake-like form as a solid phase (or solid phase), the biodegradable particles and / or water-soluble polymers contained in the formulation (or composite) can minimize degradation even when stored (or preserved) over a long period of time. Therefore, when using the formulation (or composite) according to the present invention as a material (or material) for a filling composition (or filler composition or filler composition) for orthopedic surgery (or plastic surgery or plastic surgery), the shelf life (or shelf life) of the material (or material) can be extended, and the convenience (or convenience) of storage (or storage or storage) and handling (or operation or handling) can be improved.

[0012] Furthermore, since the filling composition (or filler composition or filler composition) for orthopedic surgery (or plastic surgery or plastic surgery) according to the present invention is a dispersion of a formulation (or composite) having excellent dispersibility (or dispersibility), even when an operator (or operator or operator) (a person performing this procedure (or procedure)) applies a relatively small force to a syringe (or syringe), the procedure (or procedure) can be easily performed.

Brief Description of the Drawings

[0013]

Figure 1

Figure 2

Figure 3

Figure 4

Mode for Carrying Out the Invention

[0014] (Detailed Description of the Invention) (Best Mode for Carrying Out the Invention) Hereinafter, the present invention will be described in detail. In the present disclosure, the present invention is not limited to what is described below. Rather, the present invention can be modified in various forms without changing the gist of the present invention.

[0015] In this specification, the term "comprising" is intended to specifically indicate a particular characteristic (or characteristic), region (or region), step (or step), process (or process or method), element (or configuration or element) and / or component (or component). This does not exclude the presence or addition of other characteristics (or characteristics), regions (or regions), steps (or steps), processes (or processes or methods), elements (or configurations or elements) and / or components (or components) unless specifically stated to the contrary.

[0016] In this specification, when an element (or configuration or element) is described as being combined or combined, it means all cases where an element (or configuration or element) is directly or indirectly combined or combined with another element (or configuration or element) via another element (or configuration or element).

[0017] In this specification, unless otherwise specifically described, singular expressions are understood to include singular or plural expressions when interpreted from the context.

[0018] All numerical values and expressions regarding the amounts of components (or ingredients) used in this disclosure, reaction conditions, etc. may be modified by the term "about" unless otherwise stated.

[0019] Throughout the description of the embodiments, terms such as first (or first) and second (or second) are used to describe various components (or ingredients). However, such components (or ingredients) should not be limited by these terms. These terms are used only for the purpose of distinguishing one component (or ingredient) from another component (or ingredient).

[0020] (Formulation (or composite)) The formulation (or composite) according to the present invention may be a formulation (or composite) containing a biocompatible (or biocompatibility) and / or biodegradable (or biodegradability) material (or material). Specifically, the formulation (or composite) according to the present invention comprises biodegradable particles (or biodegradable particles or biodegradable particles) and a water-soluble polymer (or water-soluble polymer or water-soluble polymer), and the formulation is formulated (or compounded) in a cake form (or has a cake-like formulation (or compound) or cake formulation). Each of the biodegradable particles has a network structure (or network structure or network structure) in the particle. Hereinafter, the formulation will be described in detail.

[0021] (Biodegradable particles (or biodegradable particles)) The biodegradable particles (or biodegradable particles or biodegradable particles) contained in the formulation (or composite) according to the present invention function to restore (or restore) or replace (or replace) damaged or deteriorated human tissues (e.g., skin tissue).

[0022] The biodegradable particles may each be particles having a network structure (or network structure or network structure) in the particles. Specifically, a three-dimensional network structure (regular (or regular), irregular (or irregular) or a combination thereof) may be formed inside (or inside or inside) each of the biodegradable particles. Since a network structure exists inside each of the biodegradable particles, such biodegradable particles may have high strength. Thereby, human tissues can be efficiently restored (or restored) or replaced (or replaced). Furthermore, since such biodegradable particles have high strength, the strength (or strength) of the formulation (or composite) containing such particles increases. Thereby, the convenience (or convenience) of handling (or operability or handling) of the formulation is improved.

[0023] The biodegradable particles may generally contain biodegradable polymers known in the art. Specifically, the biodegradable particles may include, but are not limited to, at least one selected from the group consisting of polylactic acid (PLA), polyglycolic acid (PGA), poly(D,L-lactic acid-co-glycolic acid) (PLGA), polycaprolactone (PCL), polyvalerolactone (PVL), polyhydroxybutyrate (PHB), and polyhydroxyvalerate (PBV). Preferably, the biodegradable particles may be particles of polylactic acid (PLA).

[0024] The weight average molecular weight of the biodegradable particles may be from 50,000 to 400,000 g / mol, but is not limited thereto. Specifically, the weight average molecular weight of the biodegradable particles may be from 60,000 to 350,000 g / mol, from 70,000 to 300,000 g / mol, from 90,000 to 250,000 g / mol, from 100,000 to 200,000 g / mol, from 130,000 to 190,000 g / mol, or from 150,000 to 180,000 g / mol. When the weight average molecular weight of the biodegradable particles is within the above range, the treatment (or processing) of the formulation (or composite) can be easily carried out, and the dispersibility (or dispersibility) of the formulation (or composite) can be improved (or increased).

[0025] The tap (or tapped) density of the biodegradable particles may be from 0.1 to 0.25 g / ml, but is not limited to this range. Specifically, the tap density of the biodegradable particles may be 0.1 to 0.24 g / ml, 0.11 to 0.23 g / ml, 0.12 to 0.21 g / ml, 0.13 to 0.18 g / ml, or 0.13 to 0.17 g / ml. When the tap density of the biodegradable particles is within the above range, the biodegradable particles can be densely distributed in the formulation. Thereby, the strength (or strength) of the formulation is increased, and the dispersibility (or dispersibility) of the formulation is increased.

[0026] On the other hand, the particle size distribution (or particle diameter distribution or particle size distribution or particle - size distribution) (PSD) of the biodegradable particles may follow the following equation and may be 0.4 to 2.5, 0.5 to 2.2, 0.6 to 2.0, 0.65 to 1.9, 0.7 to 1.8, 0.8 to 1.7, 1.0 to 2.5, 1.0 to 2.3, 1.0 to 2.0, 1.01 to 1.6, 1.02 to 1.5, 1.03 to 1.4, or 1.05 to 1.3, but is not limited thereto. When the particle size distribution of the biodegradable particles is within the above range, the formulation may have excellent dispersibility (or dispersibility) in the solvent. Furthermore, when such a formulation is used as a material for a filling composition for plastic surgery, even when a thin injection needle is used, by applying a small force to the syringe, the injection (or injection) of the filling composition for plastic surgery can be successfully performed.

[0027] [Equation 1] PSD=(Dv(90)-Dv(10)) / Dv(50)

[0028] In Equation 1, Dv(10) is the size (or dimension or magnitude) at which the distribution of biodegradable particles (or biodegradable particle distribution) is within 10% [in the distribution of biodegradable particles, it is the size (or dimension or magnitude) of the particles at the 10% position (or position) listed (or listed) from the diameter (or particle diameter or particle size) of the smallest particles (based on volume (or volume or volume or volume))]. Dv(50) is the size (or dimension or magnitude) at which the distribution of biodegradable particles (or biodegradable particle distribution) is within 50% [in the distribution of biodegradable particles, it is the size (or dimension or magnitude) of the particles at the 50% position (or position) listed (or listed) from the diameter (or particle diameter or particle size) of the smallest particles (based on volume (or volume or volume or volume))]. Dv(90) is the size (or dimension or magnitude) at which the distribution of biodegradable particles (or biodegradable particle distribution) is within 90% [in the distribution of biodegradable particles, it is the size (or dimension or magnitude) of the particles at the 90% position (or position) listed (or listed) from the diameter (or particle diameter or particle size) of the smallest particles (based on volume (or volume or volume or volume))].

[0029] Specifically, in Equation 1, Dv(10) may be 5 - 35 μm, 7 - 33 μm, 10 - 30 μm, 11 - 28 μm, 12 - 25 μm or 12 - 22 μm, but is not limited thereto. Dv(50) may be 10 - 50 μm, 13 - 47 μm, 15 - 45 μm, 17 - 43 μm, 19 - 42 μm or 20 - 42 μm, but is not limited thereto. Dv(90) may be 20 - 90 μm, 25 - 85 μm, 27 - 82 μm, 29 - 80 μm, 30 - 78 μm or 32 - 75 μm, but is not limited thereto.

[0030] (Water-soluble polymer (or water-soluble polymer or water-soluble polymer)) The water-soluble polymer (or water-soluble polymer or water-soluble polymer) contained in the formulation (or composite) according to the present invention functions as a carrier (or carrier) for transporting (or transporting) biodegradable particles and functions as a matrix (or matrix) for dispersing and fixing biodegradable particles.

[0031] The water-soluble polymer may include polymers having commonly known water-soluble properties (or properties). Specifically, the water-soluble polymer may include at least one selected from the group consisting of hyaluronic acid (HA), methylcellulose (MC), ethylcellulose (EC), carboxymethylcellulose (CMC), hydroxymethylcellulose (HMC), hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), hydroxymethyl methacrylate (HEMA), polyvinyl alcohol (PVOH), polyvinylpyrrolidone (PVP), and starch, but is not limited thereto. Preferably, the water-soluble polymer may be hyaluronic acid (HA). Specifically, the water-soluble polymer may be non-crosslinked hyaluronic acid.

[0032] Hyaluronic acid (HA) is a high molecular weight hyaluronic acid (for example, sodium hyaluronate cross-polymer and sodium hyaluronate); Medium-molecular-weight hyaluronic acid (e.g., hydroxypropyltrimonium hyaluronate and sodium acetylated hyaluronate); Low-molecular-weight hyaluronic acid (e.g., potassium hyaluronate, hydrolyzed hyaluronic acid, and hydrolyzed sodium hyaluronate); Ultra-low-molecular-weight hyaluronic acid (e.g., hyaluronic acid), or a combination thereof may be used.

[0033] The weight-average molecular weight of the water-soluble polymer may be from 1,000,000 to 4,000,000 g / mol, but is not limited thereto. Specifically, the weight-average molecular weight of the water-soluble polymer may be from 1,200,000 to 4,000,000 g / mol, from 1,300,000 to 4,000,000 g / mol, from 1,500,000 to 4,000,000 g / mol, from 1,800,000 to 4,000,000 g / mol, from 2,000,000 to 4,000,000 g / mol, from 2,100,000 to 3,800,000 g / mol, or from 2,200,000 to 3,600,000 g / mol. When the weight-average molecular weight of the water-soluble polymer is within the above range, the treatment (or processing) of the formulation can be easily performed, and the dispersibility (or dispersibility) of the formulation can be improved (or increased).

[0034] According to the present invention, the weight ratio of biodegradable particles to water-soluble polymer may be from 40:60 to 95:5, but is not limited to such a range. Specifically, the weight ratio of biodegradable particles to water-soluble polymer contained in the formulation may be from 45:55 to 95:5, from 45:55 to 90:10, from 50:50 to 90:10, from 55:45 to 85:15, from 60:40 to 85:15, from 65:35 to 85:15, from 70:30 to 85:15, from 75:25 to 85:15, from 80:20 to 85:15, or from 70:30 to 80:20. When the weight ratio is within the above range, the formulation is excellent in dispersibility (or dispersibility), and the formulation can be effectively used as a material (or material) for a filling composition (or filler composition or filler composition) for plastic surgery (or plastic surgery or plastic surgery).

[0035] On the other hand, the compressive strength (or compressive strength) of the formulation according to the present invention may be 0.02 to 1.5 MPa, but is not limited to such a range. Specifically, the compressive strength of the formulation according to the present invention may be 0.025 to 1.3 MPa, 0.03 to 1.2 MPa, 0.033 to 1.0 MPa, 0.035 to 1.0 MPa, 0.035 to 0.8 MPa, 0.035 to 0.6 MPa, 0.036 to 0.5 MPa, 0.036 to 0.45 MPa, 0.036 to 0.43 MPa, 0.037 to 0.4 MPa, 0.037 to 0.39 MPa, 0.037 to 0.38 MPa or 0.037 to 0.37 MPa.

[0036] Furthermore, the apparent volume (or apparent volume or apparent volume or apparent volume or apparent volume) of the formulation (or composite) according to the present invention may be 10 to 40 ml / g, but is not limited to such a range. Specifically, the apparent volume of the formulation according to the present invention may be 10 to 35 ml / g, 10 to 32 ml / g, 10 to 30 ml / g, 12 to 29 ml / g, 14 to 29 ml / g, 15 to 28 ml / g, 15.5 to 28 ml / g or 16 to 28 ml / g.

[0037] Furthermore, the porosity (or porosity or porosity) of the formulation according to the present invention may be 90 to 97.5% by volume (or volume% or volume% or volume% or vol%), but is not limited to such a range. Specifically, the porosity (or porosity or porosity) of the formulation according to the present invention may be 90 to 97% by volume, 90 to 96% by volume or 90 to 95% by volume. Porosity (or porosity or porosity) may mean the volume (or volume or capacity or volume) of pores (or holes or pores) present in the formulation out of the total volume (or total volume or total capacity or total volume) of the formulation.

[0038] When the compressive strength, apparent density and porosity of the formulation according to the present invention are within the above specific ranges, the formulation may be excellent in long-term storage (or storage or storage), handling (or operability or handling) convenience (or convenience) and dispersibility (or dispersibility). In particular, since the compressive strength of the formulation according to the present invention is adjusted within a specific range, when the formulation is dispersed in a solvent for preparing (or manufacturing) a filling composition (or filler composition or filler composition) for plastic surgery (or plastic surgery or plastic surgery), the formulation can be uniformly dispersed within a short period of time.

[0039] Specifically, the suspension time (or suspension time) of the formulation according to the present invention in an aqueous solvent may be 30 minutes or less, but is not limited to such a range. More specifically, the suspension time of the formulation according to the present invention in an aqueous solvent may be 1 to 30 minutes, 5 to 30 minutes, 10 to 30 minutes, 10 to 29 minutes, 10 to 25 minutes, 10 to 20 minutes or 12 to 19 minutes. In the present disclosure, the aqueous solvent may specifically be water, distilled water, deionized water, ultrapure water (or ultrapure water), etc., but is not limited thereto.

[0040] The formulation according to the present invention may be in a cake-like formulated (or compounded) form (or a form having a cake-like formulation (or compound) or a cake formulation) having a fluffy texture (or fluffy feel or fluffy touch or fluffy texture). When the formulation is formulated (or compounded) in a cake-like form, it can have excellent storability (or preservability or storage) over a long period of time and dispersibility (or dispersibility) in a solvent.

[0041] Specifically, the formulation according to the present invention may have a cylindrical shape, but is not limited to such a shape. Furthermore, the average diameter (or mean diameter or average diameter or average diameter) of the formulation may be 1 to 5 cm, 1 to 3 cm, 1 to 2.5 cm, 1.2 to 2.2 cm or 1.5 to 2.0 cm, but is not limited thereto. The average height (or mean height or average height or average height) of the formulation may be 0.2 to 5 cm, 0.3 to 3 cm, 0.5 to 3 cm or 0.5 to 2.5 cm, but is not limited thereto.

[0042] (Process (or step or method) for preparing (or manufacturing or forming) a formulation (or composite)) The present invention can provide a process (or step or method) for preparing (or manufacturing or forming) the above formulation (or composite). Specifically, the process (or step or method) for preparing (or manufacturing or forming) the formulation (or composite) according to the present invention includes the following steps (or steps) (1) to (6). (1) A step of dissolving a biodegradable raw material (or raw material) in a first solvent (or first solvent) to prepare (or manufacture or form) a biodegradable solution. (2) A step of spraying (or spraying or spraying) the above biodegradable solution into a second solvent (or second solvent) to form biodegradable particles, wherein each of the above biodegradable particles has a network structure (or network structure or network structure) in the particles, and the second solvent has a freezing point (or freezing point or freezing point or freezing point) lower than that of the first solvent. (3) A step of sorting (or sorting or sorting) the above biodegradable particles by size (or size or dimension). (4) A step of adding the biodegradable particles sorted (or sorted or sorted) by the above size (or size or dimension) to a solution of a water-soluble polymer to prepare (or manufacture or form) a mixed solution. (5) A step of filling the above mixed solution into a container (or container), and (6) A step of freeze-drying (or freeze-drying) the mixed solution filled in the above container to form a formulation (or composite), wherein the above formulation is formulated (or formulated) in a cake shape (or has a cake-shaped formulation (or formulation) or cake formulation).

[0043] Step (or step) (1) is a step of dissolving a biodegradable raw material (or raw material) in a first solvent (or first solvent) to prepare (or manufacture or form) a biodegradable solution. Specifically, step (or step) (1) may be performed by adding a biodegradable raw material to a first solvent (or first solvent). In the first solvent, two or more organic solvents are mixed and stirred.

[0044] Specifically, the biodegradable raw material (or raw materials) may include, but are not limited to, at least one selected from the group consisting of polylactic acid (PLA), polyglycolic acid (PGA), poly(D,L-lactic acid-co-glycolic acid) (PLGA), polycaprolactone (PCL), polyvalerolactone (PVL), polyhydroxybutyrate (PHB), and polyhydroxyvalerate (PBV).

[0045] The weight-average molecular weight of the biodegradable raw material (or raw materials) may be 50,000 to 400,000 g / mol, but is not limited to such a range. Specifically, the weight-average molecular weight of the biodegradable raw material may be 60,000 to 350,000 g / mol, 70,000 to 300,000 g / mol, 90,000 to 250,000 g / mol, 100,000 to 200,000 g / mol, 130,000 to 190,000 g / mol, or 150,000 to 180,000 g / mol.

[0046] The first solvent (or first solvent) may specifically be at least two selected from the group consisting of dimethyl sulfoxide, diethyl sulfoxide, ethylene carbonate, propylene carbonate, dimethyl carbonate, N-methyl-2-pyrrolidone, N-ethyl-2-pyrrolidone, N-hydroxyethyl-2-pyrrolidone, N-cyclohexyl-2-pyrrolidone, N-methylformamide, N,N-dimethylformamide, N-ethylformamide, N,N-ethylformamide, N-methylacetamide, N,N-dimethylacetamide, N,N-diethylacetamide, isopropyl acetate, ethyl acetate, methyl acetate, dimethyl ketone, diethyl ketone, methyl ethyl ketone, isopropyl ketone, methyl propyl ketone, methyl butyl ketone, methyl isobutyl ketone and tetrahydrofuran, but is not limited thereto.

[0047] Specifically, it may be a solvent in which the first organic solvent and the second organic solvent are mixed at a weight ratio of 70:30 to 98:2, 75:25 to 98:2, 80:20 to 95:5, 85:15 to 95:5 or 85:15 to 90:10. More specifically, the first solvent may be a solvent (or mixed solvent) obtained by mixing dimethyl sulfoxide and ethylene carbonate, but is not limited thereto.

[0048] Step (or step) (2) is a step of spraying (or spraying or spraying) the above biodegradable solution into a second solvent (or second solvent) to form biodegradable particles, wherein each of the above biodegradable particles has a network structure (or network structure or network structure) in the particles, and the second solvent has a freezing point (or freezing point or freezing point or freezing point) lower than that of the first solvent. Specifically, step (2) may be performed by spraying a biodegradable solution into a second solvent. The second solvent can be separated in the phase without mixing with the first solvent and has a freezing point (or ice point or freeze point or freezing point) lower than that of the first solvent by 50 to 150 °C (specifically, 90 to 120 °C lower).

[0049] During the spraying (or spray or spraying), the temperature of the second solvent may specifically be -45 to 0 °C, -40 to -5 °C, -35 to -10 °C, or -30 to -10 °C, but is not limited to these ranges. When the temperature of the second solvent is within the above range, biodegradable particles can be sufficiently formed. Such biodegradable particles have a desired particle size distribution (or particle diameter distribution or particle size distribution or particle size distribution) and have a network structure (or network structure or network structure) in the particles.

[0050] The second solvent may be at least one selected from the group consisting of pentane, hexane, heptane, octane, nonane, and decane, but is not limited thereto.

[0051] The spraying rate (or spray rate or spray speed) of the biodegradable solution sprayed into the second solvent may be 1 to 20 ml / min, 3 to 15 ml / min, or 5 to 10 ml / min, but is not limited to these ranges.

[0052] Step (3) is a step of sorting the above biodegradable particles by size (or size or dimension). Specifically, step (3) may be performed by supplying the biodegradable particles to a particle sorter (or particle sorter or particle sorter) to select particles having a desired size (or size or dimension).

[0053] The size (or magnitude or dimension) of the biodegradable particles selected through a particle sorter (or particle separator or particle sorter) is not particularly limited, but the size (or magnitude or dimension) may be such that Dv(50) (average particle diameter (or average particle size or average particle diameter)) is 10 to 60 μm (specifically, 13 to 47 μm or 15 to 45 μm). Through this step, the particle size distribution (or particle diameter distribution or particle size distribution or particle size distribution) of the biodegradable particles can be adjusted to a specific range. When preparing (or manufacturing or forming) a formulation using biodegradable particles having a controlled particle size distribution (or particle diameter distribution or particle size distribution or particle size distribution), a formulation (or composite) having excellent dispersibility (or dispersibility) in a solvent can be provided.

[0054] Step (4) is a step of adding the above-mentioned biodegradable particles sorted (or sorted or sorted) by size to a solution of a water-soluble polymer in order to prepare (or manufacture or form) a mixed solution. Specifically, step (4) may be performed by adding the biodegradable particles sorted (or sorted or sorted) by size to a solution containing a water-soluble polymer at a controlled concentration and stirring it.

[0055] The water-soluble polymer contained in the solution of the water-soluble polymer may specifically include at least one selected from the group consisting of hyaluronic acid (HA), methylcellulose (MC), ethylcellulose (EC), carboxymethylcellulose (CMC), hydroxymethylcellulose (HMC), hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), hydroxymethyl methacrylate (HEMA), polyvinyl alcohol (PVOH), polyvinylpyrrolidone (PVP), and starch, but is not limited thereto.

[0056] The weight-average molecular weight of the water-soluble polymer may be 1,000,000 to 4,000,000 g / mol, but is not limited to such a range. Specifically, the weight-average molecular weight of the water-soluble polymer may be 1,200,000 to 4,000,000 g / mol, 1,300,000 to 4,000,000 g / mol, 1,500,000 to 4,000,000 g / mol, 1,800,000 to 4,000,000 g / mol, 2,000,000 to 4,000,000 g / mol, 2,100,000 to 3,800,000 g / mol, or 2,200,000 to 3,600,000 g / mol.

[0057] The content (or content or content) of the water-soluble polymer contained in the solution of the water-soluble polymer may be 0.2 to 2% by weight, 0.4 to 1.5% by weight, 0.5 to 1.3% by weight, less than 0.5 to 1% by weight, or 0.6 to 0.95% by weight based on the total weight of the solution of the water-soluble polymer, but is not limited to these ranges. When the content of the water-soluble polymer is within the above range, the strength of the formulation (or composite) may be guaranteed. On the other hand, the dispersibility (or dispersibility) of the formulation in the solvent can be increased.

[0058] The solvent contained in the solution of the water-soluble polymer may commonly be a known aqueous solvent (e.g., water, distilled water, etc.).

[0059] On the other hand, the solution of the water-soluble polymer and the biodegradable particles may be mixed such that the weight ratio (a:b) of the water-soluble polymer (a) to the biodegradable particles (b) contained in the solution of the water-soluble polymer is 40:60 to 95:5, 45:55 to 95:5, 45:55 to 90:10, 50:50 to 90:10, 55:45 to 85:15, 60:40 to 85:15, 65:35 to 85:15, 70:30 to 85:15, 75:25 to 85:15, 80:20 to 85:15 or 70:30 to 80:20.

[0060] Step (5) is a step of filling the mixed solution into a container (or container). Specifically, step (5) can be performed by filling the above mixed solution into a specific container (or container) to form a formulation (or composite). The formulation is formulated (or prepared) in a cake form (or has a cake-like formulation or cake formulation).

[0061] The container (or container) may specifically be a sealable (or sealable) glass bottle (or sealable glass bottle) (e.g., a glass bottle (or vial)), but is not limited to such a container.

[0062] The amount of the mixed solution filled into the container may be 10 to 80% by volume, 15 to 70% by volume, 15 to 65% by volume, 20 to 60% by volume or 25 to 55% by volume based on the total volume (or total volume or total volume) of the container, but is not limited to these ranges. When the filling amount of the mixed solution is within the above range, the formulation (or composite) is formulated (or prepared) in a cake form (or has a cake-like formulation (or preparation) or cake formulation), and a formulation having a desired compressive strength can be formed.

[0063] Step (6) is a step of lyophilizing (or freeze-drying) the above mixed solution filled in the above container (or container) to form a formulation (or composite), and formulating (or preparing) the formulation in a cake form (or having a cake-like formulation (or preparation) or cake formulation). Specifically, step (6) may include the following steps (6-1) to (6-4). (6-1) A step of freezing the above mixed solution at -60 to -10 °C to obtain a frozen product. (6-2) A first heating step of heating the above frozen product to a temperature of -5 to 5 °C over 1 to 3 hours under reduced pressure. (6-3) A second heating step of heating the above frozen product (however, after the first heating step) to a temperature of 20 to 25 °C over 8 to 15 hours under reduced pressure, and (6-4) A drying step of drying the above frozen product (however, after the second heating step) at a temperature of 25 °C or higher over 20 to 40 hours under reduced pressure.

[0064] In step (6-1), the temperature for freezing the mixed solution may be -60 to -10 °C, -50 to -20 °C or -40 to -30 °C, but is not limited to these ranges. Furthermore, the time for freezing the mixed solution may be 60 to 240 minutes, 90 to 180 minutes or 120 to 150 minutes, but is not limited to these ranges.

[0065] Steps (6-2) to (6-4) are steps of drying (or evaporating or vaporizing) the solvent present in the frozen product by gradually increasing the temperature of the frozen product. In such cases, the degree of final vacuum in each step may be 0.1 to 30 mTorr, 0.5 to 20 mTorr or 1 to 10 mTorr, but is not limited to these ranges.

[0066] Specifically, step (6-2) may be carried out by first increasing the temperature of the frozen product (-60°C to -10°C) to a temperature of -5 to 5°C, -3 to 3°C or -1 to 1°C over 1 to 3 hours or 1.5 to 2.5 hours under reduced pressure.

[0067] Step (6-3) may be carried out by secondarily increasing the temperature to which the frozen product was first increased to a temperature of 20 to 25°C, 22 to 25°C or 24 to 25°C over 8 to 15 hours or 9 to 11 hours under reduced pressure.

[0068] To finally dry the product, step (6-4) may be carried out by increasing the temperature to which the frozen product was secondarily increased to a temperature of 25°C or higher (specifically, 25 to 30°C) over 20 to 40 hours or 22 to 30 hours under reduced pressure.

[0069] When lyophilizing the mixed solution by steps (6-1) to (6-4), a formulation (or composite) in the form of a cake (or formulated or compounded in the form of a cake or having a cake formulation) can be effectively formed.

[0070] On the one hand, the process (or step or method) for preparing (or manufacturing or forming) the formulation (or composite) according to the present invention may further include a step (or step) of sterilizing (or disinfecting) the formulation (or composite).

[0071] The sterilization (or disinfection) may be performed by sterilization (or disinfection) with gamma rays (or γ rays), sterilization (or disinfection) with an electron beam (or e-beam), sterilization (or disinfection) with ethylene oxide, sterilization (or disinfection) with steam (or steam), or sterilization (or disinfection) with high-pressure steam (or steam), but is not limited thereto. Specifically, sterilization (or disinfection) may be performed using ethylene oxide at 30 to 40 °C for 150 to 180 minutes. By such a procedure (or procedure), the long-term storage stability (or storage stability or storage) of the formulation can be further improved (or increased or improved).

[0072] The size (or size or dimension) of the biodegradable particles contained in the formulation (or composite) prepared (or manufactured or formed) by the above preparation process (or manufacturing process) is not particularly limited, but the average particle diameter (or average particle size or average particle size or average particle diameter) (average particle diameter) (Dv(50)) may be 15 to 60 μm. Specifically, the biodegradable particles may be such that the first biodegradable particles have a Dv(50) particle size distribution (or particle size distribution or particle size distribution) of 15 to 30 μm, 17 to 29 μm, 18 to 28 μm, 19 to 27 μm, 20 to 25 μm, or 21 to 23 μm, but are not limited thereto. The biodegradable particles may be such that the second biodegradable particles have a Dv(50) particle size distribution (or particle size distribution or particle size distribution) greater than 30 and up to 60 μm, greater than 30 and up to 55 μm, 35 to 50 μm, 35 to 48 μm, 38 to 45 μm, or 40 to 43 μm, but are not limited thereto. Alternatively, the biodegradable particles may be a mixture of the first biodegradable particles and the second biodegradable particles, but are not limited thereto.

[0073] Specifically, the particle size distribution (or particle diameter distribution or particle size distribution or particle - size distribution) (PSD) of the biodegradable particles contained in the formulation (or composite) prepared (or manufactured or formed) by the above - mentioned preparation process (or manufacturing process) follows the following equation and may be 0.4 - 2.5, 0.5 - 2.2, 0.6 - 2.0, 0.65 - 1.9, 0.7 - 1.8, 0.8 - 1.7, 1.0 - 2.5, 1.0 - 2.3, 1.0 - 2.0, 1.01 - 1.6, 1.02 - 1.5, 1.03 - 1.4 or 1.05 - 1.3, but is not limited to these ranges.

[0074] [Equation 1] PSD=(Dv(90)-Dv(10)) / Dv(50)

[0075] In Equation 1, Dv(10) is the size (or dimension) at which the distribution (or distribution) of the biodegradable particles is within 10%. Dv(50) is the size (or dimension) at which the distribution (or distribution) of the biodegradable particles is within 50%. Dv(90) is the size (or dimension) at which the distribution (or distribution) of the biodegradable particles is within 90%.

[0076] In the present invention, a mixed solution obtained by mixing biodegradable particles having a specific particle size distribution (or particle diameter distribution or particle size distribution or particle - size distribution) and a solution of a water - soluble polymer is filled into a sealable container (or sealable container or sealable container), and the formulation (or composite) is prepared (or manufactured or formed) by freeze - drying (or freeze - drying) it. Therefore, a formulation (or composite) can be obtained which is formulated (or compounded) in a specific cake-like form (or has a specific cake-like formulation or specific cake formulation), and moreover has a controlled (or managed or controlled) compressive strength (or compressive strength).

[0077] Since the formulation according to the present invention is formulated (or compounded) in a cake-like form (or has a cake-like formulation or cake formulation), it is excellent in long-term storage stability (or storage stability or storage) and dispersibility (or dispersibility), and the convenience (or convenience) of handling (or operation or handling) is improved (or increased). These are due to the advantage (or virtue) of the controlled (or managed or controlled) compressive strength (or compressive strength). Furthermore, since the formulation according to the present invention contains biodegradable particles and a water-soluble polymer, it can have biocompatibility (or biocompatibility) and biodegradability (or biodegradability).

[0078] Therefore, the formulation (or composite) according to the present invention can be advantageously used as a material (or material) for restoring (or repairing or restoring) or replacing (or substituting or replacing) human tissues. Furthermore, the formulation (or composite) according to the present invention can be used as a carrier (or carrier) for cells (or cells) or drugs (or drugs), a culture medium (or culture medium) for cells, etc.

[0079] A filling composition (or filler composition or filler composite) for plastic surgery (or plastic surgery or plastic surgery) The present invention provides a filling composition (or filler composition or filler - composition) for plastic surgery (or plastic surgery or plastic surgery). In such a filling composition, the above - mentioned formulation (or composite) is dispersed. Specifically, in the filling composition (or filler composition or filler - composition) for plastic surgery (or plastic surgery or plastic surgery) according to the present invention, the formulation (or composite) is dispersed in a solvent, and the formulation may have the same composition (or prescription or composition) and characteristics (or characteristics) as those described above.

[0080] The filling composition (or filler composition or filler - composition) for plastic surgery (or plastic surgery or plastic surgery) according to the present invention can prepare (or manufacture or form) the filling composition in a short period of time (for example, within 30 minutes) due to the advantage (or virtue) of the improved dispersibility (or dispersibility) of the formulation. That is, when using a sealed formulation (or composite) that is formulated (or compounded) in a solid - phase cake - like form (or having a cake - like formulation (or compound) or cake - formulation), the solubility (or solubility or solubility) and dispersibility (or dispersibility) are improved (or increased or improved). Thereby, the filling composition (or filler composition or filler - composition) for plastic surgery (or plastic surgery or plastic surgery) can be prepared (or manufactured or formed) within a short period of time. Therefore, in the present invention, the filling composition (or filler composition or filler - composition) for plastic surgery (or plastic surgery or plastic surgery) can be easily prepared (or manufactured or formed) immediately before the procedure (or procedure). Furthermore, since the composition (or composite) contains biodegradable particles having a controlled particle size distribution (or particle diameter distribution or particle size distribution or particle - size distribution), the filling composition (or filler composition or filler composition) for plastic surgery (or plastic surgery or plastic surgery) of the present invention obtained by dispersing the composition in a solvent allows the operator (or operator or operator) to easily perform the procedure (or procedure). On the other hand, even when using a needle (or needle) with a small diameter (or diameter), a small force (or force) is applied to the syringe (or syringe). Therefore, the filling composition (or filler composition or filler composition) for plastic surgery (or plastic surgery or plastic surgery) according to the present invention can reduce the discomfort and fatigue of the operator (or operator or operator). On the other hand, it improves the operation (or surgery or surgery) environment.

[0081] For example, in the filling composition (or filler composition or filler composition) for plastic surgery (or plastic surgery or plastic surgery) according to the present invention (for example, a composition formed by dispersing a composition having an average particle diameter (or average particle size or average particle diameter) (Dv(50)) of 60 μm or less), the injection force (or injection force or injection force) regarding an injection needle (or injection needle) with a gauge (G) of 26 may be 2.0 N or less, specifically, it may be 0.3 - 1.5 N, 0.5 - 1.3 N, 0.7 - 1.25 N or 0.9 - 1.20 N, but it is not limited to these ranges. Furthermore, in a filling composition (or filler composition or filler - composition) for orthopedic surgery (or plastic surgery or plastic - surgery) according to the present invention (for example, a composition formed by dispersing a formulation having an average particle diameter (or average grain size or average - particle - diameter) (Dv(50)) of 33 μm or less), the injection force (or injection pressure or injection power) regarding an injection needle (or injection - needle) with a gauge (G) of 30 may be 3.0 N or less. Specifically, it may be 1.6 - 2.6 N, 1.7 - 2.4 N, 1.8 - 2.2 N, or 1.9 - 2.0 N, but is not limited to these ranges.

[0082] Embodiments (or modes) of the invention Hereinafter, the present invention will be described in detail with reference to examples. However, the scope of the present invention is not limited to the following examples.

Examples

[0083] Example 1 9 g of polylactic acid (PLA) (weight - average molecular weight = 170,000 g / mol) was dissolved in 150 ml of a mixed solvent (a mixed solvent of dimethyl sulfoxide and ethylene carbonate) (weight ratio of dimethyl sulfoxide:ethylene carbonate = 90:10) to obtain a solution of polylactic acid.

[0084] Next, the polylactic - acid solution prepared as described above was sprayed (or sprayed) onto n - hexane (cooled to - 20°C or lower) (spray rate (or spray - rate)=4.5 ml / min, spray air volume (or spray - air - volume)=6 liters / min) to form frozen polylactic - acid particles in n - hexane. The frozen polylactic - acid particles formed as described above were obtained, added to water (1 - 3°C), and stirred to remove the mixed solvent (a mixed solvent of dimethyl sulfoxide and ethylene carbonate) contained in the frozen polylactic - acid particles. Thereby, polylactic - acid particles (PLA particles) were prepared.

[0085] Subsequently, using a particle sorter (or particle sorter or particle sorter), the polylactic acid particles prepared as described above were sorted to obtain polylactic acid particles (particle diameter: 60 μm or less) (Dv(50): 41.9 μm).

[0086] Next, the polylactic acid particles (particle diameter: 60 μm or less) were added to a sodium hyaluronate solution (concentration: 0.6%) (HA solution = 99.4 wt% distilled water + 0.6 wt% sodium hyaluronate). By doing so, the weight ratio of polylactic acid particles:sodium hyaluronate (HA) became 85:15, and subsequently, by mixing them, a mixed solution was prepared.

[0087] Next, 5.20 g of the mixed solution thus prepared (170 mg of PLA particles and 30 mg of HA) was filled into a 10 ml glass bottle (or vial).

[0088] Next, the mixed solution filled in the glass bottle was frozen at -40 to -30 °C to obtain a frozen product (or frozen product). The temperature of the frozen product thus obtained was first raised from -30 °C to 0 °C over 2 hours under reduced pressure. Next, the temperature was raised again from 0 °C to 25 °C over 10 hours. Next, it was dried at 25 °C over 24 hours to form a formulation (or composite) in the glass bottle (or vial).

[0089] Thereafter, the glass bottle containing this formulation was sterilized using ethylene oxide (EO) gas. And by drying under reduced pressure, the remaining moisture (or moisture) was removed, and in the glass bottle, a formulation (or composite) having a diameter (or diameter) of 1.8 cm and a height (or height) of 2.2 cm was prepared (or manufactured).

[0090] Examples 2 to 4 Each formulation was prepared according to the same procedure (or procedure) as in Example 1. However, with respect to the concentration of sodium hyaluronate (HA) contained in the mixed solution filled in the glass bottle, the amount of the mixed solution to be filled, the diameter (or diameter) and height (or height) of the formulation, they were adjusted as shown in Table 1 below.

[0091]

Table 1

[0092] Example 5 According to the same procedure (or procedure) as in Example 1, a formulation (or composite) (diameter (or diameter): 1.8 cm, height (or height): 0.55 cm) was prepared. However, a particle sorter (or particle sorter or particle sorter) was used to select polylactic acid particles to obtain polylactic acid particles with a particle diameter (or particle size) of 33 μm or less (Dv(50): 21.1 μm), and this was added to the sodium hyaluronate solution.

[0093] Comparative Example 1 According to the same procedure (or procedure) as in Example 1, a formulation (or composite) (diameter (or diameter): 1.8 cm) was prepared. However, a glass bottle was filled with a mixed solution (170 mg of PLA particles and 30 mg of HA) and dried under reduced pressure at 25 °C for 16 hours (that is, a sterilization process was performed without freeze-drying).

[0094] Test Example 1: Observation of the formulation (or preparation) (or formulation) The formulations (or composites or formulations) of the formulations prepared in Example 1, Example 5 and Comparative Example 1 were visually observed. The results are shown in Figure 2.

[0095] Referring to FIG. 2, the formulations (or composites) of Example 1 and Example 5 were formulated (or compounded) in a cake shape (or had a cake-shaped formulation (or compound) or cake formulation) (cylindrical shape (or cylinder shape)). In contrast, the formulation (or composite) of Comparative Example 1 did not have a regular shape (or regular shape or regular shape). This was because the mixed solution swelled during the process (or step or method) of drying under reduced pressure.

[0096] In the present disclosure, the formulations (or composites) of Example 1 and Example 5 were formulated (or compounded) in a cake shape (or had a cake-shaped formulation (or compound) or cake formulation). According to the present invention, the dispersibility (or dispersibility) can be increased, and a convenient formulation (or composite) can be used. This can be confirmed in Test Examples 7 and 8 below.

[0097] Test Example 2: Observation of the internal structure of polylactic acid particles and the structure of the formulation

[0098] The formulations (or composites) prepared in Example 1 and Example 5 were cut (or sliced) in the vertical direction, and the cross-section was observed using a scanning electron microscope (manufacturer: Hitachi High Technology, model name: Hitachi su5000). The results are shown in FIGS. 3 and 4.

[0099] Referring to what is shown in FIGS. 3(a) and 4(a), in the formulations (or composites) of Example 1 and Example 5, the polylactic acid particles each maintained their shape and were uniformly present inside (or inside or inside) the formulation (or composite).

[0100] Furthermore, referring to what is shown in FIGS. 3(b) and 4(b), the polylactic acid particles present in the formulations (or composites) of Example 1 and Example 5 each had a network structure (or mesh structure or network structure) in the particles.

[0101] Test Example 3: Measurement of Tap Density In each of Example 1 and Example 5, the tap density of the polylactic acid (PLA) particles obtained by the process (or step or method) of sorting (or sorting or sorting) using a particle sorter (or particle sorter or particle sorter) was measured according to the following measurement method. The results are shown in Table 2 below.

[0102] * Method for Measuring Tap Density

[0103] (1) The weight of the graduated cylinder was measured, and 20 - 25 ml of polylactic acid particles were placed in the graduated cylinder.

[0104] (2) The weight of the graduated cylinder containing the polylactic acid particles was measured, and the weight of only the polylactic acid particles was calculated.

[0105] (3) The graduated cylinder containing the polylactic acid particles was placed (or mounted) on a tap density meter (manufacturer: Bettersize, model name: BeDensi T1 Pro).

[0106] (4) The tap density meter was operated (or run) under the conditions of a tapping speed (or tapping speed): 250 times / minute and a tapping count (or tapping count): 1250 times.

[0107] (5) After the tapping was completed, the graduated cylinder was taken out, and the volume (or volume or volume or volume) of the polylactic acid particles was measured.

[0108] (6) The weight of the polylactic acid particles measured in step (2) was divided by the volume (or capacity or volume or bulk) of the polylactic acid particles measured in step (5) to calculate the tap density (or tap density). (The tap density was measured for each of the five samples (or specimens), and the average value was obtained).

[0109]

Table 2

[0110] Referring to Table 2 above, the polylactic acid particles prepared in each of Example 1 and Example 5 had a tap density in the range of 0.1 to 0.2 g / ml. Here, in Example 5, the particle size (or particle diameter or particle size or particle size) of the polylactic acid particles was smaller compared to Example 1. In Example 5, the tap density of the polylactic acid particles was larger compared to Example 1. Therefore, it is expected that a high-density bonding is achieved inside the formulation (or composite).

[0111] Test Example 4: Measurement of Particle Size Distribution For the polylactic acid particles prepared in each of Example 1 and Example 5, the particle size distribution (or particle diameter distribution or particle size distribution or particle size distribution) was measured according to the following measurement method. The results are shown in Table 3 below.

[0112] * Method for Measuring Particle Size Distribution

[0113] (1) The formulation (or composite) was added to water and stirred for 30 minutes to prepare a suspension (or suspension).

[0114] (2) For the prepared suspension, the particle size distribution (or particle diameter distribution or particle size distribution or particle size distribution meter) (manufacturer: Malvern Instrument, model name: Mastersizer 3000 - Maz6140) was used for analysis to measure the particle size distribution (or particle diameter distribution or particle size distribution or particle size distribution) of the polylactic acid particles.

[0115] (3) Using the following Equation 1, the particle size distribution (or particle diameter distribution or particle size distribution or particle size distribution) (particle size distribution) (PSD) was calculated from the values measured in step (or step) (2).

[0116] [Equation 1] PSD = (Dv(90) - Dv(10)) / Dv(50)

[0117] In Equation 1, Dv(10) is the size (or size or dimension) at which the distribution of the biodegradable particles is within 10%. Dv(50) is the size (or size or dimension) at which the distribution of the biodegradable particles is within 50%. Dv(90) is the size (or size or dimension) at which the distribution of the biodegradable particles is within 90%.

[0118] [Table 3]

[0119] Referring to Table 3 above, the particle size distribution (or particle diameter distribution or particle size distribution or particle size distribution) of the polylactic acid particles prepared in each of Example 1 and Example 5 was in the range of 1.0 to 2.5. Here, when the particle size distribution (or particle diameter distribution or particle size distribution or particle - size distribution) of the polylactic acid particles is within the above - mentioned range, according to the present invention, the convenience (or utility) of the use of the formulation (or composite) can be increased. That is, when the particle size distribution (or particle diameter distribution or particle size distribution or particle - size distribution) is within the above - mentioned range, the formulation (or composite) is excellent in dispersibility (or dispersibility). Even when a relatively small force (injection force (or injection force or injection force)) is applied to a syringe (or syringe) filled with a suspension (or suspension) in which the formulation (or composite) is dispersed, the suspension (or suspension) is discharged (or injected) smoothly. This can be confirmed in Test Examples 7 and 8 below.

[0120] Test Example 5: Measurement of Compressive Strength Using an Instron 5848 (model name) instrument (measurement conditions - compression speed: 10 mm / min, maximum compression ratio: 75%), the compressive strength (or compressive strength) of the formulations (or composites) prepared in each of Examples 1 - 4 and Comparative Example 1 was measured. The results are shown in Table 4 below.

[0121]

Table 4

[0122] Referring to Table 4 above, the compressive strength (or compressive strength) of each of the formulations (or composites) in Examples 1 - 4 was in the range of 0.03 - 1 MPa. Furthermore, it is understood that the concentration of sodium hyaluronate (HA) affects the compressive strength (or compressive strength) of the formulation (or composite).

[0123] On the other hand, since the formulation (or composite) of Comparative Example 1 had an irregular shape, the compressive strength could not be measured.

[0124] Test Example 6: Measurement of Apparent Volume The apparent volume of the formulations (or composites) prepared in each of Examples 1 to 4 and Comparative Example 1 was measured using the diameter and height of the formulation (or composite). The results are shown in Table 5 below.

[0125]

Table 5

[0126] Referring to Table 5 above, the apparent volume of each of the formulations (or composites) of Examples 1 to 4 was in the range of 10 to 40 ml / g. Furthermore, it is understood that in order to increase the porosity (or porosity or porosity) of the formulation (or composite), it is desirable that the concentration of sodium hyaluronate (HA) is lower. Here, when the formulation (or composite) has a high porosity (or porosity or porosity), the formulation (or composite) can be rapidly suspended in an aqueous solvent during use. Thereby, the convenience of use of the formulation (or composite) can be increased. This can be confirmed in Test Example 7 and Test Example 8 below.

[0127] On the other hand, since the formulation (or composite) of Comparative Example 1 had an irregular shape, the apparent volume could not be measured.

[0128] Test Example 7: Measurement of Suspension Time The suspension time (or suspension time) of the formulations (or composites) prepared in each of Examples 1 to 4 and Comparative Example 1 was measured according to the following measurement method. The results are shown in Table 6 below.

[0129] * Method for measuring suspension time

[0130] (1) 8 ml of distilled water was added to the glass bottle containing the formulation and left for about 5 minutes.

[0131] (2) The rpm of the vortex mixer was set to 3000 and the glass bottle was stirred for 5 minutes.

[0132] (3) In the glass bottle, it was visually confirmed whether the formulation (or composite) was completely dissolved and granulated.

[0133] (4) The procedure of step (2) was repeated until the formulation (or composite) was completely dissolved, and the time taken for granulation was measured.

[0134] [Table 6]

[0135] Referring to Table 6 above, each of the formulations (or composites) of Examples 1 to 4 was rapidly suspended (dispersed) with a suspension time of 30 minutes or less. Since the suspension is completed in a short period of time, the use of the formulation according to the present invention is excellent in convenience. For example, when suspending the formulation in an aqueous solvent at a treatment site (or treatment site) for treating the skin (or skin) (or skin treatment), the formulation can be suspended within a short period of time, and the efficiency (or efficiency) of the treatment (or treatment) can be increased.

[0136] Here, the suspension of the formulation (or composite) according to the present invention is possible within a short period of time. This is because the formulation (or composite) is formulated (or compounded) in a cake form (or has a cake formulation or cake formulation), and the particle size distribution (or particle size distribution or particle size distribution or particle size distribution) Compressive strength (or compressive strength) and apparent volume (or apparent volume) are within a specific range. This supports (or supports) the importance (or importance) of controlling (or managing or controlling) the shape, compressive strength, apparent volume and particle size distribution of the polylactic acid particles contained in the formulation (or composite).

[0137] Furthermore, it was confirmed that the lower the concentration of sodium hyaluronate (HA), the shorter the suspension time. Therefore, in order to enhance the convenience (or convenience) of using the formulation (or composite), it is desirable to control (or manage or control) the concentration of hyaluronic acid. Thereby, a support structure (or support structure) (frame) of the formulation (or composite) is formed.

[0138] Test Example 8: Measurement of injection force (or injection force or injection force) The injection force (or injection force or injection force) of the formulations (or composites) prepared in Example 1 and Example 5 respectively was measured according to the following measurement method. The results are shown in Table 7 below.

[0139] *Method for Measuring Injection Force (or Injection Input or Injection Power)

[0140] (1) 5 ml of distilled water was added to a glass bottle containing the formulation (or composite), and it was stirred with a vortex mixer until the formulation (or composite) was dissolved and granulated (until a suspension was prepared).

[0141] (2) In the glass bottle, 0.5 - 0.6 ml of the suspension was filled into a 1 ml disposable syringe (or disposable syringe).

[0142] (3) A 26G or 30G injection needle (or injection needle) was attached to the syringe (or syringe). Then, the syringe (or syringe) was fixed with the needle (or needle) facing downward to the support (or support) of a universal testing machine (manufacturer: TestOne, model name: TO - 102).

[0143] (4) The universal testing machine (universal test machine) was operated, and the push bar attached to the injection tube was pushed at 1 mm / second until the injection tube was completely empty, and the measured force (or force) was recorded.

[0144] (5) In the graph where the measured force was recorded, calculate the average value (input force) of the force measured at a position (or point) 5 mm to the right of the starting position (or start point), a position (or point) 5 mm to the left of the ending position (or end point), and the intermediate position (or midpoint) between these two positions (or points).

[0145]

Table 7

[0146] Referring to Table 7 above, the injection force (or injection power or injection strength) of the formulations (or composites) of Example 1 and Example 5 was low. Therefore, even when a relatively small force was applied, the suspension (or suspension) in which the formulation (or composite) was dispersed was smoothly discharged from the syringe (or syringe). Since the injection force (or injection power or injection strength) is small in this way, the formulation (or composite) according to the present invention is excellent in usability (or convenience). For example, when using the suspension (or suspension) in which the formulation (or composite) is dispersed at the treatment site (or treatment site), the suspension is smoothly discharged from the syringe (or syringe), and even when a relatively small force (or force) is applied to the syringe (or syringe), it is injected (or injected or injected) into the skin (or skin). Therefore, the convenience (or convenience) of the procedure (or procedure) can be improved.

[0147] Also, such results support the importance (or importance) of controlling (or managing or controlling) the shape, compressive strength, apparent volume and particle size distribution of the polylactic acid particles contained in the formulation (or composite).

Claims

1. A complex, wherein the complex comprises biodegradable particles and a water-soluble polymer, and is a cake-like preparation, and wherein each of the biodegradable particles has a network structure in the particles.

2. The complex according to claim 1, wherein the compression strength of the complex is 0.02 to 1.5 MPa.

3. The complex according to claim 1, wherein the apparent volume of the complex is 10 to 40 ml / g.

4. The complex according to claim 1, wherein the tap density of the complex is 0.1 to 0.25 g / ml.

5. The complex according to claim 1, wherein the weight ratio of the biodegradable particles to the water-soluble polymer is 40:60 to 95:

5.

6. The complex according to claim 1, wherein the biodegradable particles comprise at least one selected from the group consisting of polylactic acid (PLA), polyglycolic acid (PGA), poly(D,L-lactic acid-co-glycolic acid) (PLGA), polycaprolactone (PCL), polyvalerolactone (PVL), polyhydroxybutyrate (PHB), and polyhydroxyvalerate (PBV).

7. The complex according to claim 1, wherein the water-soluble polymer comprises at least one selected from the group consisting of hyaluronic acid (HA), methylcellulose (MC), ethylcellulose (EC), carboxymethylcellulose (CMC), hydroxymethylcellulose (HMC), hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), hydroxymethyl methacrylate (HEMA), polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), and starch.

8. The complex according to claim 1, wherein the suspension time of the complex in an aqueous solvent is 30 minutes or less.

9. A process for preparing a complex, the process comprising the following steps (1) to (6): （１） A step of dissolving a biodegradable raw material in a first solvent to prepare a biodegradable solution; （２） A step of spraying the biodegradable solution into a second solvent to form biodegradable particles, wherein each of the biodegradable particles has a network structure in the particles, and the second solvent has a freezing point lower than that of the first solvent; （３） A step of sorting the biodegradable particles by size; （４） A step of adding the biodegradable particles sorted by size to a solution of a water-soluble polymer to prepare a mixed solution. （５） A step of filling the container with the mixed solution, and （６） A step of freeze-drying the mixed solution filled in the container to form a complex, wherein the complex is formulated into a cake-like shape A process comprising the steps of

10. In the freeze-drying step of the step (6), the following steps (6-1) to (6-4): （６－１） A step of freezing the mixed solution at -60 to -10 °C to obtain a frozen product （６－２） A first heating step of heating the frozen product to a temperature of -5 °C to 5 °C over 1 to 3 hours under reduced pressure （６－３） A second heating step of heating the frozen product (however, after the first heating step) to a temperature of 20 °C to 25 °C over 8 to 15 hours under reduced pressure, and （６－４） A drying step of drying the frozen product (however, after the second heating step) at a temperature of 25 °C or higher over 20 to 40 hours under reduced pressure A process for preparing the complex according to claim 9, comprising the steps of

11. In the step (4), the content of the water-soluble polymer contained in the solution of the water-soluble polymer is 0.2 to 2% by weight based on the total weight of the solution of the water-soluble polymer. A process for preparing the complex according to claim 9

12. A filling composition for plastic surgery in which the complex according to any one of claims 1 to 8 is dispersed

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