Polymer filler composition containing biodegradable polymer nanoparticles and manufacturing method thereof

Abstract

This invention relates to a polymer filler composition containing biodegradable polymer nanoparticles and a method for preparing the same. Specifically, the polymer filler composition containing biodegradable polymer nanoparticles according to the invention utilizes screened nanoparticles of a specific size, allowing for easy injection into the dermis or subcutaneous tissue via tiny particles. Furthermore, the polymer filler composition according to the invention has the advantages of promoting the generation of collagen at the injection site to increase volume and elasticity, improve wrinkles, and being safe to use due to its complete absorption in the body, while minimizing pain and foreign body sensation experienced by the patient after injection.

Description

Technical Field

[0001] The present invention relates to a polymer filler composition containing biodegradable polymer nanoparticles and a method for preparing the same. Prior Art

[0002] The era aiming to eliminate diseases, the era striving to achieve the wish for longevity, and the era endeavoring to live a healthy life have passed. Recently, the era reflecting people's pursuit of youth and beauty has arrived. According to the above social situation, people's attention to preventing or delaying aging has significantly increased.

[0003] However, aging is a universal and inevitable life phenomenon experienced by all mankind, and the deep and shallow wrinkles that appear on the face are natural results of the aging process. In particular, the reduction of endogenous hyaluronic acid, one of the causes of aging, reduces the water supply to the skin, resulting in a decrease in tissue elasticity and the formation of wrinkles, a characteristic of aging. Therefore, various methods for improving this phenomenon are constantly being studied.

[0004] The methods for improving wrinkles can be classified into products and services such as skin treatments, functional cosmetics, fillers, botulinum toxins, and beauty services that make the appearance look younger. Among them, fillers are used to smooth the wrinkled areas and fill the space inside the skin by directly injecting them into the skin of the facial wrinkle areas, so as to visually improve the wrinkles.

[0005] In other words, fillers are materials or compositions designed to increase the volume of the missing areas of soft tissues that connect, support, or surround other structures and organs of the body such as muscles, tendons, fibrous tissues, fats, blood vessels, nerves, and synovial tissues. It refers to the materials injected or inserted into the skin to supplement the materials inside the skin in order to improve skin wrinkles. According to the development process, filler products are divided into four generations, and the latest is the filler preparation using biocompatible polymers, that is, a preparation developed and used by processing water-insoluble polymers into micron-sized particles and then dispersing them through a viscous biocompatible carrier.

[0006] On the other hand, according to Klaus Laeschke, ‘Biocompatibility of Microparticles into Soft Tissue Fillers’, “Semin Cutan Med Surg 23” 2004, 214-217, in the case of polymer-based products for tissue repair, in order to avoid phagocytosis in the body and exert long-term efficacy, a particle size of 40 µm or more is required. However, when using the above-mentioned preparations with a particle size of 40 µm or more, there are surgical inconveniences caused by microparticle clogging of the needle, and there are problems such as difficulty in achieving a uniform tissue repair effect due to non-uniform dispersion of the particles. In addition, there are problems such as instability of the particle shape and size or a relatively long time required for collagen production in the skin.

[0007] Therefore, the inventors recognized the need to study a filler containing biodegradable polymer nanoparticles that are not phagocytosed by macrophages even after being injected into the human body, so that their volume can be maintained, and the size and distribution of the nanoparticles remain uniform. At the same time, the nanoparticles have a small size and are relatively spherical. In addition, focusing on the need to develop a polymer filler that can minimize the pain and foreign body sensation felt by patients after injection by being injectable through a fine needle, the present invention was completed. Prior Art Documents Patent Documents Korean Patent No. 10-2483759 (December 28, 2022) Summary of the Invention

[0008] The present invention aims to solve the problems of the above-mentioned prior art and provide a polymer filler composition containing biodegradable polymer nanoparticles and a method for preparing the same. The polymer filler composition of the present invention is a biodegradable polymer material that induces collagen production after being injected into the human body and has a relatively long retention period, and has the characteristic of small particle size. Therefore, the technical problem to be solved by the polymer filler composition of the present invention is to minimize the pain and foreign body sensation felt by patients after injection by being injectable through a fine needle. However, the technical problems to be solved by the embodiments of the present invention are not limited to the above technical problems, and there may be other technical problems.

[0009] Therefore, an object of the present invention is to provide a polymer filler composition, which is a polymer filler composition containing biodegradable polymer nanoparticles. The above nanoparticles are spherical, the particle size of the above nanoparticles is 50 nm to 1,000 nm, the number average molecular weight (Mn) of the above biodegradable polymer is 10,000 g / mol to 100,000 g / mol, and relative to 100% by weight of the above polymer filler composition, the content of the above nanoparticles is 10% to 50% by weight. The above biodegradable polymer is at least one selected from the group consisting of polylactic acid, polycaprolactone, derivatives thereof, and copolymers thereof.

[0010] Another object of the present invention is to provide a method for preparing a polymer filler composition, which includes: Step 1) dissolving a biodegradable polymer in an organic solvent to form a polymer solution; Step 2) preparing an aqueous surfactant solution; Step 3) adding the above polymer solution to the above aqueous surfactant solution to form a crude emulsion as a mixture; Step 4) dispersing the above crude emulsion under high pressure to prepare a nanoparticle emulsion; and Step 5) preparing nanoparticles by removing the solvent and water from the above emulsion. The above crude emulsion is dispersed under high pressure at an extrusion pressure of 500 bar to 2,000 bar. The above biodegradable polymer is at least one selected from the group consisting of polylactic acid, polycaprolactone, derivatives thereof, and copolymers thereof. The above surfactant is at least one selected from the group consisting of polyvinyl alcohol, methylcellulose, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, poloxamer 188, poloxamer 123, and poloxamer 407. Technical means for solving the problem

[0011] To achieve the above object, the present invention provides a polymer filler composition, which is a polymer filler composition containing biodegradable polymer nanoparticles. The above nanoparticles are spherical, the particle size of the above nanoparticles is 50 nm to 1,000 nm, the number average molecular weight (Mn) of the above biodegradable polymer is 10,000 g / mol to 100,000 g / mol, and relative to 100% by weight of the above polymer filler composition, the content of the above nanoparticles is 10% to 50% by weight. The above biodegradable polymer is at least one selected from the group consisting of polylactic acid, polycaprolactone, derivatives thereof, and copolymers thereof.

[0012] In addition, the present invention provides a method for preparing a polymer filler composition, which includes: Step 1) dissolving a biodegradable polymer in an organic solvent to form a polymer solution; Step 2) preparing an aqueous surfactant solution; Step 3) adding the above polymer solution to the above aqueous surfactant solution to form a crude emulsion as a mixture; Step 4) subjecting the above crude emulsion to high-pressure dispersion to prepare a nanoparticle emulsion; and Step 5) preparing nanoparticles by removing the solvent and water from the above emulsion; the above crude emulsion is subjected to high-pressure dispersion at an extrusion pressure of 500 bar to 2,000 bar, the above biodegradable polymer is at least one selected from the group consisting of polylactic acid, polycaprolactone, their derivatives, and their copolymers, and the above surfactant is at least one selected from the group consisting of polyvinyl alcohol, methyl cellulose, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, poloxamer 188, poloxamer 123, and poloxamer 407. Efficacy compared with the prior art

[0013] The polymer filler composition containing biodegradable polymer nanoparticles according to the present invention has the following effects, that is, by applying nanoparticles of a selected size, the fine particles are easily injected into the dermis or subcutaneous tissue, and skin tissue regeneration and wrinkle improvement can be achieved, and the pain and foreign body sensation felt by the patient after injection can also be minimized. In addition, the polymer filler composition containing biodegradable polymer nanoparticles according to the present invention has the following advantages, that is, it promotes the generation of its own collagen at the injection site of the above polymer filler composition to increase volume and elasticity, improve wrinkles, and it can be completely and safely absorbed in the body. Brief description of the drawings

[0014] Figure 1 shows the results of injecting a polycaprolactone nanoparticle filler, which is a polymer filler composition according to Example 9 and Comparative Example 1, into the back of a rat.

[0015] Figure 2 shows a flowchart of a method for preparing a polymer filler composition containing biodegradable polymer nanoparticles according to the present invention. Embodiments

[0016] Unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by those skilled in the art to which the present invention belongs. Generally, the nomenclature used in this specification is well-known and commonly used in the technical field.

[0017] Hereinafter, the present invention will be described in more detail.

[0018] The present invention provides a polymer filler composition, which is a polymer filler composition containing biodegradable polymer nanoparticles. The nanoparticles are spherical, the particle diameter of the nanoparticles is 50 nm to 1,000 nm, the number average molecular weight (Mn) of the biodegradable polymer is 10,000 g / mol to 100,000 g / mol, and the content of the nanoparticles is 10% by weight to 50% by weight based on 100% by weight of the polymer filler composition. The biodegradable polymer is at least one selected from the group consisting of polylactic acid, polycaprolactone, derivatives thereof, and copolymers thereof.

[0019] The biodegradable polymer according to the present invention can be at least one selected from the group consisting of polylactic acid, polycaprolactone, derivatives thereof, and copolymers thereof. Preferably, the biodegradable polymer can be polylactic acid or polycaprolactone, and more preferably, the biodegradable polymer can be polycaprolactone.

[0020] In order to maintain a filler retention period of more than two years, preferably, the number average molecular weight (Mn) of the biodegradable polymer according to the present invention can be 10,000 g / mol to 100,000 g / mol, and more preferably, it can be 10,000 g / mol to 50,000 g / mol.

[0021] Preferably, the particle shape of the nanoparticles according to the present invention is substantially spherical so that it does not cause pain to the patient and is not tactilely perceptible.

[0022] For injection applications, the particle size of the nanoparticles should be smaller than the diameter of the needle used for injection. Therefore, the nanoparticle size (particle diameter) can generally be 800 nm or less. Preferably, the particle size of the nanoparticles can be 50 nm to 1,000 nm, more preferably, it can be 80 nm to 900 nm, and even more preferably, it can be 80 nm to 500 nm. On the other hand, when using particles with a micron-sized particle diameter used in existing filler compositions as a formulation, it may cause surgical inconvenience due to clogging of the needle by fine particles, and it is difficult to achieve a uniform tissue repair effect due to non-uniform dispersion of the particles. In addition, there are problems such as unstable particle shape and size, or a long time required for collagen production in the skin. To solve the above problems, the particles contained in the filler composition of the present invention have a nanoscale particle diameter.

[0023] The above biodegradable polymer nanoparticles according to the present invention can be prepared using solvent evaporation, precipitation methods, and cooling pulverization methods commonly used in the technical field to which the present invention pertains. On the other hand, according to an embodiment of the present invention, in the present invention, a high-pressure disperser is used to prepare the biodegradable polymer nanoparticles. According to an embodiment of the present invention, the above nanoparticles can be highly dispersed under an extrusion pressure of 500 bar to 2,000 bar.

[0024] The above polymer filler composition according to the present invention contains biodegradable polymer nanoparticles made of a polymer having biocompatibility and biodegradability.

[0025] Preferably, based on 100% by weight of the polymer filler composition, the amount of nanoparticles contained in the above polymer filler composition according to the present invention can be 10% to 50% by weight, more preferably 10% to 30% by weight, but is not limited thereto, and can be adjusted according to the desired volume effect of the desired injection site.

[0026] The above polymer filler composition according to the present invention may further contain a biocompatible carrier. The above biocompatible carrier is generally absorbed into the body within 1 day to 6 months after injecting the polymer filler composition. The above biocompatible carrier can be at least one selected from the group consisting of polyethylene glycol, carboxymethyl cellulose, hyaluronic acid, dextran, collagen, and glycerin.

[0027] Preferably, based on 100% by weight of the polymer filler composition, the amount of the biocompatible carrier contained in the above polymer filler composition according to the present invention can be 50% to 90% by weight, more preferably 70% to 90% by weight.

[0028] The above polymer filler composition according to the present invention can be formulated into various forms for administration to an individual. Preferably, the polymer filler composition according to the present invention is an injectable formulation. The above polymer filler composition can be an injectable formulation administered to an individual using a 27G to 32G needle, and the injection rate of the above polymer filler composition can be 5 mm / minute to 15 mm / minute.

[0029] As the above-mentioned individual according to the present invention, there is no limitation as long as it is a mammal such as livestock or humans to which the above polymer filler composition can be applied, but it is preferably a human.

[0030] The injection preparation of the polymer filler composition according to the present invention can be provided in a state of being contained in a sterile syringe or a sterile vial. It is convenient to use without pretreatment, and can be 100% biodegradable within a predetermined time after injection. Therefore, it does not leave foreign substances in biological tissues, is safe, and has the advantage of not causing allergies because it does not contain any animal-derived substances. Therefore, the polymer filler composition according to the present invention can be used for wrinkle improvement, facial plastic surgery or body plastic surgery.

[0031] The polymer filler composition according to the present invention may further include at least one selected from the group consisting of buffers, preservatives, isotonic agents, antioxidants, emulsifiers, and wetting agents, but is not limited thereto, and may include other pharmaceutically acceptable components.

[0032] The polymer filler composition according to the present invention may further include other substances or combinations of substances that provide beneficial effects when administered to an individual. These beneficial substances include, but are not limited to, antioxidants, anti-itch agents, anti-cellulite agents, anti-scar agents, anti-inflammatory agents, anesthetics, irritation relievers, vasoconstrictors, vasodilators, anti-hemorrhagic agents such as hemostatic agents, or antifibrinolytics, exfoliants, elastogenic agents, anti-acne agents, colorants, anti-pigmentation agents, or moisturizers.

[0033] The polymer filler composition according to the present invention can be sterile. For example, it can be sterilized by an autoclave or by heat, pressure, gamma ray irradiation, etc. In any specific embodiment of the above forms, the composition located subcutaneously or intradermally can provide an immediate "repair" effect due to its cohesive or viscoelastic properties. This smooths the lines and wrinkles on the skin and can provide the appearance of skin restoration.

[0034] The polymer filler composition according to the present invention can be used as a facial filler for injection in a small amount of less than about 0.1 mL to 10 mL, and can also be used as a filler for injection in a large volume of 10 mL to 200 mL, but is not limited thereto.

[0035] The polymer filler composition according to the present invention can be for at least one soft tissue selected from the group consisting of the face, neck, chest, buttocks, arms, armpits, hands, legs, and feet.

[0036] The above polymer filler composition according to the present invention can be used for the repair of skin tissue, the above polymer filler composition can be used for improving skin wrinkles and reducing tissue volume, and can be used for treating wounds or stretch marks, but is not limited thereto.

[0037] In addition, the present invention provides a method for preparing a polymer filler composition, which includes: Step 1) dissolving a biodegradable polymer in an organic solvent to form a polymer solution; Step 2) preparing an aqueous surfactant solution; Step 3) adding the above polymer solution to the above aqueous surfactant solution to form a coarse emulsion as a mixture; Step 4) subjecting the above coarse emulsion to high-pressure dispersion to prepare a nanoparticle emulsion; and Step 5) preparing nanoparticles by removing the solvent and water from the above emulsion; the above coarse emulsion is subjected to high-pressure dispersion at an extrusion pressure of 500 bar to 2,000 bar, the above biodegradable polymer is at least one selected from the group consisting of polylactic acid, polycaprolactone, derivatives thereof, and copolymers thereof, and the above surfactant is at least one selected from the group consisting of polyvinyl alcohol, methyl cellulose, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, poloxamer 188, poloxamer 123, and poloxamer 407.

[0038] According to an embodiment of the present invention, after the above Step 5), a step of mixing the above nanoparticles with a biocompatible carrier or water for injection may further be included.

[0039] On the other hand, the description of the technical features that overlap with the technical features of the above nanoparticles and polymer filler composition among the components of the above preparation method will be omitted.

[0040] Hereinafter, the present invention will be described in more detail through examples. Hereinafter, the present invention will be described in detail with reference to preferred embodiments so that those of ordinary skill in the technical field to which the present invention pertains can easily implement the present invention. These examples are only used to more specifically explain the present invention, and the scope of the present invention is not limited by these examples. [Example 1] Preparation of Biodegradable Polymer Nanoparticles

[0041] To prepare biodegradable polymer nanoparticles, polycaprolactone (PCL) was dissolved in dichloromethane to prepare a 10 w / v% polymer solution. Polyvinyl alcohol (PVA) was dissolved in distilled water to prepare a 2 w / v% PVA aqueous solution. The volume ratio of the polymer solution to the aqueous solution was set to 1:2. A homogenizer was used to prepare a coarse emulsion. As the homogenizer conditions, stirring was carried out at 3,000 rpm for 15 minutes. The prepared coarse emulsion was made into a nanoparticle dispersion by a high-pressure disperser. The polymer nanoparticles were obtained by evaporating the solvent and water in the nanoparticle dispersion. At this time, as the high-pressure disperser conditions, the extrusion pressure was repeated 5 times at 1,500 bar. [Example 2] Preparation of Biodegradable Polymer Nanoparticles

[0042] The same process as in Example 1 was carried out, and the extrusion pressure in the conditions of the high-pressure disperser was set to 1,000 bar. [Example 3] Preparation of Biodegradable Polymer Nanoparticles

[0043] The same process as in Example 1 was carried out, and the extrusion pressure in the conditions of the high-pressure disperser was set to 500 bar. [Example 4] Preparation of Biodegradable Polymer Nanoparticles

[0044] The same process as in Example 1 was carried out, and polyvinyl alcohol (PVA) was dissolved in distilled water to prepare a 2 w / v% PVA aqueous solution. The volume ratio of the polymer solution to the aqueous solution was set to 1:5. [Example 5] Preparation of Biodegradable Polymer Nanoparticles

[0045] The same process as in Example 1 was carried out, and polyvinyl alcohol (PVA) was dissolved in distilled water to prepare a 1 w / v% PVA aqueous solution. The volume ratio of the polymer solution to the aqueous solution was set to 1:5. [Example 6] Preparation of Polymer Filler Composition

[0046] A polycaprolactone filler was prepared by mixing carboxymethyl cellulose gel in which carboxymethyl cellulose was dissolved in the water for injection of the nanoparticle dispersion of Example 1. [Example 7] Preparation of Polymer Filler Composition

[0047] Perform the same process as in Example 6 and use the nanoparticle dispersion of Example 2. [Example 8] Preparation of polymer filler composition

[0048] Perform the same process as in Example 6 and use the nanoparticle dispersion of Example 3. [Example 9] Preparation of polymer filler composition

[0049] Prepare a polycaprolactone filler by mixing a sodium hyaluronate gel in which sodium hyaluronate is dissolved with the water for injection of the nanoparticle dispersion of Example 1. [Comparative Example 1] Set up a control group

[0050] Set the existing commercially available facial filler GOURI (batch number: A47422001) from Dexlevo Company made of polycaprolactone as the control group. [Experimental Example 1] Measurement of particle size of polycaprolactone nanoparticles

[0051] Measure the particle sizes of Examples 1 to 3. The particle sizes are measured using Mastersizer 3000D from Malvern Company, and the particle size analysis results are shown in Table 1. Examples 1 to 3 are based on polycaprolactone nanoparticles prepared at extrusion pressures of 1,500 bar, 1,000 bar, and 500 bar in a high-pressure disperser. When the extrusion pressure of the high-pressure disperser is set to 1,500 bar, 1,000 bar, and 500 bar, the Dv(50) values are 260 nm, 243 nm, and 329 nm, respectively. 1,500 bar and 1,000 bar show similar values, and 500 bar shows a lower value. It has been confirmed that as the extrusion pressure of the high-pressure disperser increases, the size of the polycaprolactone nanoparticles decreases. Table 1 Classification Example 1 Example 2 Example 3 Dv(10) [nm] 129 119 150 Dv(50) [nm] 260 243 329 Dv(90) [nm] 507 475 741 [Experimental Example 2] Measurement of particle size of polycaprolactone nanoparticles

[0052] Measure the particle sizes of Example 1 and Examples 4 to 5. The Mastersizer 3000D from Malvern was used to measure the particle sizes. The results of particle size analysis are shown in Table 2. In Example 1 and Examples 4 to 5, polycaprolactone nanoparticles were prepared according to the content ratio of polyvinyl alcohol and the volume ratio of the polymer solution and the aqueous solution. Comparing the nanoparticles with a polyvinyl alcohol content ratio of 2 w / v% and volume ratios of the polymer solution to the aqueous solution of 1:2 and 1:5 respectively, it was found that the size of the nanoparticles with a volume ratio of the polymer solution to the aqueous solution of 1:5 was smaller than that of the nanoparticles with a volume ratio of the polymer solution to the aqueous solution of 1:2. In addition, comparing the nanoparticles with a ratio of the polymer solution to the aqueous solution of 1:5 and polyvinyl alcohol content ratios of 2 w / v% and 1 w / v% respectively, it was found that the size of the nanoparticles with a polyvinyl alcohol content ratio of 2 w / v% was smaller than that of the nanoparticles with a polyvinyl alcohol content ratio of 1 w / v%. Table 2 Classification Example 1 Example 4 Example 5 Dv(10) [nm] 129 100 127 Dv(50) [nm] 260 200 250 Dv(90) [nm] 507 406 468 [Experimental Example 3] Measurement of particle diameter of polycaprolactone nanoparticle filler

[0053] Measure the particle sizes of Examples 6 to 9 and Comparative Example 1. Use a Mastersizer 3000 from Malvern to measure the particle sizes. The particle size analysis results are shown in Table 3. The particle sizes of Examples 6 to 9 are generally smaller than those of Comparative Example 1, and the average values of their particle sizes show a more uniform and narrower distribution. Table 3 Classification Example 6 Example 7 Example 8 Example 9 Comparative Example 1 Dv(10) [nm] 128 120 147 97.3 165 Dv(50) [nm] 256 243 319 196 465 Dv(90) [nm] 489 468 710 432 7,570 [Experimental Example 4] Stability evaluation of the polycaprolactone nanoparticle filler

[0054] Observe the particle size stability of the polycaprolactone filler in Example 6 for one month and evaluate its stability. The results are shown in Tables 4 and 5. As the stability evaluation, long-term stability evaluation and accelerated stability evaluation were carried out. The temperature and humidity conditions for the long-term stability evaluation were 25 ± 2 °C and relative humidity 60 ± 5% respectively, and the temperature and humidity conditions for the accelerated stability evaluation were 40 ± 2 °C and relative humidity 75 ± 5% respectively. The stability evaluation was carried out under the above conditions. When the stability of the polycaprolactone nanoparticle filler was evaluated for one month, the particle size did not change, showing stable results. Table 4 Classification (Long-term) Example 6 Week 0 Week 1 Week 2 Week 3 Week 4 Dv(10) [nm] 128 126 127 129 130 Dv(50) [nm] 256 254 255 258 258 Dv(90) [nm] 489 491 489 493 487 Table 5 Classification (Acceleration) Example 6 Week 0 Week 1 Week 2 Week 3 Week 4 Dv(10) [nm] 128 130 131 128 127 Dv(50) [nm] 256 260 259 256 254 Dv(90) [nm] 489 495 489 488 488 [Experimental Example 5] Measurement of the injection site size of animals administered with a polycaprolactone nanoparticle filler

[0055] After filling the syringe with the polycaprolactone nanoparticle filler, 250 μl was injected into the back of the rats. The fillers of Example 9 and Comparative Example 1 were injected into the rats, and the injection sites were photographed after the fourth week and the eighth week. The dimensions of the sites where the filler was injected were measured, and the changes in dimensions were continuously measured at regular intervals. Figure 1 shows the results of photographing the filler injection sites after a certain period. Although the filler of Example 9 was not absorbed at the fourth week, the filler of Comparative Example 1 was completely absorbed at the fourth week. It can be seen from this that, compared with Comparative Example 1, Example 9 maintained the volume of the injection site for a longer time after injection. In addition, when observed with the naked eye, no side effects such as nodules were observed in the photographs. The dimensions of the injection sites were measured, and the results are shown in Table 6. As a result, Example 9 maintained the volume of the injection site, while Comparative Example 1 was completely absorbed and the dimensions could not be measured. Table 6 Classification Fourth week Example 9 [mm 3] 357.46 [Experimental Example 6] Measurement of collagen content in the injection site of animals administered with polycaprolactone nanoparticle filler

[0056] After filling the syringe with the polycaprolactone nanoparticle filler, 250 μl was injected into the back of the rats. The fillers of Example 9 and Comparative Example 1 were injected into the rats, and the collagen content in the injection site at the fourth week was measured. The collagen content was measured using a collagen assay kit. Table 6 shows the measurement results of the collagen content in the injection site. The collagen content of Example 9 was 26.56 μg / mg, while the collagen content of Comparative Example 1 could not be measured because no collagen was formed at the injection site. Table 7 Classification Fourth week Example 9 [μg / mg] 26.56 Comparative Example 1 [μg / mg] - [Experimental Example 7] Safety evaluation of animals administered with polycaprolactone nanoparticle filler

[0057] After filling the syringe with the polycaprolactone nanoparticle filler, 250 μl was injected into the back of the rats. The phosphate buffer solutions of Example 9 and Comparative Example 1 were injected into the rats, and the safety was evaluated by blood tests at week 0 and week 4. Table 7 shows the blood test results regarding the liver and kidney safety. As a result of comparing Example 9 with the phosphate buffer solution, similar values were observed, indicating that it is safe in terms of liver and kidney safety. Table 8 Classification Week 0 Week 4 AST (IU / L) ALT (IU / L) BUN (IU / L) CRE (IU / L) AST (IU / L) ALT (IU / L) BUN (IU / L) CRE (IU / L) Phosphate buffer solution 97 ± 13 49 ± 4 12.2 ± 1.4 0.39 ± 0.04 103 ± 28 41 ± 2 16 ± 1.4 0.49 ± 0.04 Example 9 92 ± 14 47 ± 7 11.5 ± 1.5 0.40 ± 0.04 79 ± 4 47 ± 4 14.4 ± 1.0 0.48 ± 0.05 Comparative Example 1 89 ± 8 48 ± 6 12.1 ± 1.5 0.38 ± 0.03 91 ± 12 47 ± 3 16.1 ± 2.1 0.46 ± 0.08

[0058] As described above, the present invention has been illustrated by the above embodiments, but the present invention is not necessarily limited thereto, and various modifications can of course be made without departing from the scope and spirit of the present invention. Therefore, the protection scope of the present invention should be understood to include all embodiments falling within the scope of the appended patent application of the present invention.

[0059] None

Claims

1. A polymer filler composition comprising biodegradable polymer nanoparticles, wherein, The nanoparticles are spherical and have a particle size of 50 nm to 1,000 nm, with a particle size of 50 nm or larger based on Dv(10) and 800 nm or smaller based on Dv(90). The number average molecular weight (Mn) of the biodegradable polymer is 10,000 g / mol to 100,000 g / mol. The content of the nanoparticles is 10% to 50% by weight relative to 100% by weight of the polymer filler composition. The biodegradable polymer is at least one selected from the group consisting of polylactic acid, polycaprolactone, and copolymers thereof.

2. The polymer filler composition as claimed in claim 1, wherein, The above-mentioned polymer filler composition also includes a biocompatible carrier.

3. The polymer filler composition as claimed in claim 2, wherein, The aforementioned biocompatible carrier is at least one selected from the group consisting of polyethylene glycol, carboxymethyl cellulose, hyaluronic acid, dextran, collagen, and glycerol.

4. The polymer filler composition of claim 2, wherein, The content of the biocompatible carrier is 50% to 90% by weight relative to 100% by weight of the above polymer filler composition.

5. The polymer filler composition of claim 1, wherein, The above-mentioned polymer filler composition further comprises at least one selected from the group consisting of buffers, preservatives, isotonic agents, antioxidants, emulsifiers and wetting agents.

6. The polymer filler composition of claim 1, wherein, Based on Dv(50), the particle size of the above nanoparticles is 196 nm or larger and 329 nm or smaller.

7. A method for preparing a polymer filler composition, comprising: Step 1) Dissolve the biodegradable polymer in an organic solvent to form a polymer solution; Step 2) Prepare an aqueous solution of the surfactant; Step 3) The polymer solution is added to the aqueous surfactant solution to form a crude emulsion as a mixture; Step 4) The crude emulsion is dispersed under high pressure to prepare a nanoparticle emulsion; and Step 5) Nanoparticles are prepared by removing solvent and water from the emulsion; wherein the crude emulsion is dispersed under high pressure at an extrusion pressure of 500 bar to 2,000 bar, the biodegradable polymer is at least one selected from the group consisting of polylactic acid, polycaprolactone, and copolymers thereof, and the surfactant is at least one selected from the group consisting of polyvinyl alcohol, methylcellulose, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, poloxamer 188, poloxamer 123, and poloxamer 407.

8. A method for preparing the polymer filler composition as claimed in claim 7, wherein, Step 5) is followed by a step of mixing the nanoparticles with a biocompatible carrier or water for injection.

9. A method for preparing the polymer filler composition as claimed in claim 8, wherein, The aforementioned biocompatible carrier is at least one selected from the group consisting of polyethylene glycol, carboxymethyl cellulose, hyaluronic acid, dextran, collagen, and glycerol.

10. A method for preparing the polymer filler composition as claimed in claim 8, wherein, The content of the biocompatible carrier is 50% to 90% by weight relative to 100% by weight of the above polymer filler composition.

11. A method for preparing the polymer filler composition as claimed in claim 7, wherein, The aforementioned nanoparticles are spherical.

12. A method for preparing the polymer filler composition as claimed in claim 7, wherein, The particle size of the above nanoparticles ranges from 50 nm to 1,000 nm, with a particle size of 50 nm or larger based on Dv(10) and a particle size of 800 nm or smaller based on Dv(90).

13. A method for preparing the polymer filler composition as claimed in claim 7, wherein, The number-average molecular weight (Mn) of the above-mentioned biodegradable polymers is from 10,000 g / mol to 100,000 g / mol.

14. A method for preparing the polymer filler composition as claimed in claim 7, wherein, The content of the nanoparticles is 10% to 50% by weight relative to 100% by weight of the above polymer filler composition.

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