Polymer filler composition containing biodegradable polymer nanoparticles and preparation method thereof
By preparing biodegradable polymer nanoparticles, the problems of needle clogging and pain caused by existing fillers are solved, and the uniform distribution of nanoparticles and collagen generation are achieved, providing skin regeneration and wrinkle improvement.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- JETEMA CO LTD
- Filing Date
- 2024-10-10
- Publication Date
- 2026-05-15
AI Technical Summary
Existing polymer fillers contain microparticles that easily clog needles, are uneven in size, cannot be evenly dispersed, and cause strong pain and foreign body sensation after injection, as well as slow collagen production.
It uses biodegradable polymer nanoparticles with a particle size of 50-1000 nm and spherical shape, prepared by high-pressure dispersion method. It contains polylactic acid, polycaprolactone and its derivatives, and the surfactant is polyvinyl alcohol, etc., to form a nanoparticle emulsion and remove the solvent, which is suitable for fine needle injection.
It achieves uniform distribution of nanoparticles, reduces injection pain and foreign body sensation, promotes collagen production, maintains the volume of the injection site and completely degrades in the body, providing skin regeneration and wrinkle improvement.
Smart Images
Figure CN122055174A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to a polymer filler composition containing biodegradable polymer nanoparticles and its preparation method. Background Technology
[0002] With the passing of an era focused on eliminating disease, striving for longer lifespans, and pursuing healthy living, recent years have witnessed an era reflecting a pursuit of youthful and beautiful lifestyles. In line with this social trend, attention has significantly increased to prevent or delay aging.
[0003] However, aging is a universal and inevitable life phenomenon that all humans experience, and the deep and shallow wrinkles that form on the face are a natural result of the aging process. In particular, the reduction of endogenous hyaluronic acid, one of the causes of aging, reduces the skin's moisture supply and ultimately leads to a decrease in tissue elasticity, thus forming wrinkles, a characteristic of aging. Therefore, various methods to improve this condition are being researched.
[0004] Methods for improving wrinkles can be categorized into skin treatments, functional cosmetics, fillers, and products and services such as botulinum toxin and beauty services that aim to make one appear younger. Among these, fillers are used to fill wrinkled areas by being injected directly into the skin in the wrinkled areas of the face to fill the space within the skin, thereby visually improving the appearance of wrinkles.
[0005] In other words, fillers refer to materials or compositions designed to increase volume in areas of soft tissue deficiency. Soft tissue refers to tissues that connect, support, or surround other structures and organs of the body, such as muscles, tendons, fibrous tissue, fat, blood vessels, nerves, and synovial tissue. Fillers are substances that can be injected or implanted into the skin to supplement internal skin tissue and thus improve skin wrinkles. Filler products can be classified into four generations based on their development process. In recent years, filler formulations using biocompatible polymers have been developed and used. These formulations involve 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, polymer-based tissue repair products need a particle size of 40 μm or larger to avoid phagocytosis in vivo and maintain long-term efficacy. However, when using formulations with particle sizes of 40 μm or larger, problems arise such as microparticles clogging needles, leading to inconvenience in operation, and particles not being evenly dispersed, thus failing to achieve uniform tissue repair effects. Furthermore, there are issues with uneven particle shape and size, and the collagen formation in the skin may take a long time.
[0007] Therefore, the inventors recognized the need to research a filler comprising biodegradable polymeric nanoparticles that, even after injection into the human body, would not be phagocytosed by macrophages, thus maintaining its volume, and while maintaining uniform size and distribution of the nanoparticles, the nanoparticles would be small and relatively spherical. Furthermore, the inventors also focused on researching a polymeric filler that could be injected through a fine needle, thereby minimizing pain and foreign body sensation experienced by the patient after injection, thus completing this invention. Summary of the Invention
[0008] The technical problem that the invention aims to solve This invention aims to solve the problems in the prior art by providing a polymer filler composition comprising biodegradable polymer nanoparticles and its preparation method. The polymer filler composition of this invention can induce collagen production after injection into the human body and is a biodegradable polymer material with a long duration of action, while also featuring a small particle size. Therefore, the polymer filler composition of this invention addresses the technical challenge of minimizing pain and foreign body sensation experienced by the patient after injection by allowing injection through a fine needle. However, the technical challenges to be achieved by the embodiments of this invention are not limited to the above-mentioned technical challenges, and other technical challenges may also exist.
[0009] Therefore, the object of the present invention is to provide a polymer filler composition comprising biodegradable polymer nanoparticles, wherein the nanoparticles are spherical in shape, the nanoparticles have a particle size of 50-1000 nm, the biodegradable polymer has a number-average molecular weight (Mn) of 10000-100000 g / mol, and the content of the nanoparticles is 10-50% by weight per 100% of the polymer filler composition, and the biodegradable polymer is one or more selected from the group consisting of polylactic acid, polycaprolactone, its derivatives and copolymers thereof.
[0010] Another object of the present invention is to provide a method for preparing a polymer filler composition, comprising the following steps: 1) dissolving a biodegradable polymer in an organic solvent to form a polymer solution; 2) preparing an aqueous surfactant solution; 3) adding the polymer solution to the aqueous surfactant solution to form a mixture, i.e., a crude emulsion; 4) subjecting the crude emulsion to high-pressure dispersion to prepare a nanoparticle emulsion; and 5) removing solvent and water from the emulsion to prepare nanoparticles; wherein the crude emulsion is subjected to high-pressure dispersion at an extrusion pressure of 500–2000 bar, and the biodegradable polymer is selected from polylactic acid (PLA). The surfactant is one or more selected from the group consisting of poly(acid), polycaprolactone, its derivatives and copolymers thereof, and the surfactant is one or more selected from the group consisting of polyvinyl alcohol, methylcellulose, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, poloxamer 188, poloxamer 123 and poloxamer 407.
[0011] means for solving problems To achieve the above objectives, the present invention provides a polymer filler composition comprising biodegradable polymer nanoparticles, wherein the nanoparticles are spherical in shape, the nanoparticles have a particle size of 50-1000 nm, the biodegradable polymer has a number-average molecular weight (Mn) of 10000-100000 g / mol, and the nanoparticles comprise 10-50% by weight of the polymer filler composition, wherein the biodegradable polymer is one or more selected from the group consisting of polylactic acid, polycaprolactone, their derivatives, and their copolymers.
[0012] Furthermore, this invention provides a method for preparing a polymer filler composition, comprising: 1) dissolving a biodegradable polymer in an organic solvent to form a polymer solution; 2) preparing an aqueous surfactant solution; 3) adding the polymer solution to the aqueous surfactant solution to form a mixture, i.e., a crude emulsion; 4) subjecting the crude emulsion to high-pressure dispersion to prepare a nanoparticle emulsion; and 5) removing solvent and water from the emulsion to prepare nanoparticles; wherein the crude emulsion is extruded at an extrusion pressure of 500–2000 bar. The biodegradable polymer is dispersed under high pressure by force, and is selected from one or more of the group consisting of polylactic acid, polycaprolactone, its derivatives and copolymers, and the surfactant is selected from one or more of the group consisting of polyvinyl alcohol, methylcellulose, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, poloxamer 188, poloxamer 123 and poloxamer 407.
[0013] The effects of the invention The polymer filler composition containing biodegradable polymer nanoparticles according to the present invention, by applying nanoparticles of a sieved size, facilitates injection into the dermis or subcutaneous tissue via microparticles, achieving skin tissue regeneration and wrinkle improvement, while minimizing pain and foreign body sensation experienced by the patient after injection. Furthermore, the polymer filler composition containing biodegradable polymer nanoparticles according to the present invention promotes autologous collagen production at the injection site, thereby achieving volume and elasticity enhancement and wrinkle improvement, and has the advantage of being safely and completely absorbed in vivo. Attached Figure Description
[0014] Figure 1 To demonstrate the results of injecting the polymer filler composition, namely polycaprolactone nanoparticle filler, according to Example 9 and Comparative Example 1 into the back of a rat.
[0015] Figure 2 A flowchart illustrating a method for preparing a polymer filler composition comprising biodegradable polymer nanoparticles according to the present invention is provided. Detailed Implementation
[0016] Unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Generally, the terms used in this specification are those well-known and commonly used in the art.
[0017] The present invention will now be described in detail.
[0018] This invention provides a polymer filler composition comprising biodegradable polymer nanoparticles, wherein the nanoparticles are spherical in shape and have a particle size of 50–1000 nm, the biodegradable polymer has a number-average molecular weight (Mn) of 10,000–100,000 g / mol, and the nanoparticles comprise 10–50% by weight of the polymer filler composition, and the biodegradable polymer is one or more selected from the group consisting of polylactic acid, polycaprolactone, their derivatives, and their copolymers.
[0019] According to the present invention, the biodegradable polymer can be one or more selected from the group consisting of polylactic acid, polycaprolactone, its derivatives, and copolymers thereof. Preferably, the biodegradable polymer can be polylactic acid or polycaprolactone, and more preferably, the biodegradable polymer can be polycaprolactone.
[0020] According to the present invention, the number average molecular weight (Mn) of the biodegradable polymer is preferably 10,000 to 100,000 g / mol, more preferably 10,000 to 50,000 g / mol, so that the filler can be maintained for more than 2 years.
[0021] According to the present invention, the nanoparticles are preferably spherical in shape, so as not to cause pain to the patient and not to be perceived by touch.
[0022] According to the present invention, the particle size of the nanoparticles should be smaller than the diameter of the injection needle used for injection. Therefore, the particle size of the nanoparticles is typically below 800 nm, preferably below 50–1,000 nm, more preferably 80–900 nm, and even more preferably 80–500 nm. On the other hand, in conventional filler compositions, when using dosage forms with micron-sized particles, there are problems such as microparticles clogging the needle, leading to inconvenience in operation, and particles not being evenly dispersed, thus failing to achieve a uniform tissue repair effect. Furthermore, there are problems such as uneven particle shape and size, or a long time required for collagen formation in the skin. To solve the above problems, the filler composition of the present invention contains particles with a nanometer-sized particle size.
[0023] According to the present invention, the biodegradable polymer nanoparticles can be prepared by solvent evaporation, precipitation, or cooling pulverization methods commonly used in the technical field to which this invention pertains. On the other hand, according to one embodiment of the present invention, a high-pressure disperser is used to prepare the biodegradable polymer nanoparticles. According to one embodiment of the present invention, the nanoparticles can be particles dispersed under high pressure at an extrusion pressure of 500–2,000 bar.
[0024] According to the present invention, the polymer filler composition comprises biodegradable polymer nanoparticles made of a polymer having biocompatibility and biodegradability.
[0025] According to the present invention, the content of nanoparticles contained in the polymer filler composition is preferably 10-50% by weight, more preferably 10-30% by weight, based on 100% by weight of the polymer filler composition, but is not limited thereto, and can be adjusted according to the target volume effect of the desired injection site.
[0026] According to the present invention, the polymer filler composition may further comprise a biocompatible carrier. The biocompatible carrier is typically absorbed by the human body within 1 day to 6 months after injection of the polymer filler composition. The biocompatible carrier may be one or more selected from the group consisting of polyethylene glycol, carboxymethyl cellulose, hyaluronic acid, dextran, collagen, and glycerin.
[0027] According to the present invention, the content of the biocompatible carrier contained in the polymer filler composition is preferably 50-90% by weight, more preferably 70-90% by weight, based on 100% by weight of the polymer filler composition.
[0028] According to the present invention, the polymeric filler composition can be prepared into various dosage forms for individual administration, preferably an injectable dosage form. The polymeric filler composition can be an injectable dosage form administered to an individual via a 27-32G injection needle, and the injection rate of the polymeric filler composition can be 5-15 mm / min.
[0029] According to the present invention, the individual is not limited, as long as it is a mammal capable of applying the polymer filler composition, such as livestock or humans, preferably humans.
[0030] According to the present invention, the injectable dosage form of the polymer filler composition can be provided in a sterile syringe or sterile vial without pretreatment, offering high convenience of use. Furthermore, it is 100% biodegradable after a predetermined time following injection, thus leaving no foreign matter residue in biological tissues. It boasts high safety and, being free of any animal-derived substances, does not cause allergies. Therefore, according to the present invention, the polymer filler composition can be used for wrinkle improvement, facial contouring, or body contouring.
[0031] According to the present invention, the polymer filler composition may further comprise one or more selected from the group consisting of buffers, preservatives, isotonic agents, antioxidants, emulsifiers and wetting agents, but is not limited thereto, and may also comprise other pharmaceutically acceptable components.
[0032] According to the present invention, the polymeric filler composition may further comprise other substances or combinations thereof that provide beneficial effects when administered to an individual. These beneficial substances include, but are not limited to, antioxidants, antipruritic agents, anti-cellulite agents, anti-scarring agents, anti-inflammatory agents, anesthetics, irritant-relieving agents, vasoconstrictors, vasodilators, antihemorrhagic agents such as hemostatic agents or antifibrinolytic agents, exfoliants, elasticity enhancers, anti-acne agents, colorants, anti-pigmentation agents, or moisturizers.
[0033] According to the present invention, the polymer filler composition can be sterile, for example, by autoclaving or sterilization by heat, pressure, gamma ray irradiation, etc. In any of the above-described embodiments, the composition located subcutaneously or intradermally can provide an immediate "lifting" effect due to its cohesive or viscoelastic properties. This can smooth lines and wrinkles on the skin, thereby providing a regenerated appearance.
[0034] According to the present invention, the polymer filler composition can be used as a facial filler injected in small volumes of about 0.1 mL to less than 10 mL, or as a filler injected in large volumes of 10 mL to 200 mL, but is not limited thereto.
[0035] According to the present invention, the polymer filler composition can be used in any soft tissue selected from the group consisting of face, neck, chest, buttocks, arms, armpits, hands, legs and feet.
[0036] According to the present invention, the polymer filler composition can be used for the repair of skin tissue, can be used to improve skin wrinkles and tissue volume reduction, and can be used for the treatment of wounds or stretch marks, but is not limited thereto.
[0037] Furthermore, this invention provides a method for preparing a polymer filler composition, comprising: 1) dissolving a biodegradable polymer in an organic solvent to form a polymer solution; 2) preparing an aqueous surfactant solution; 3) adding the polymer solution to the aqueous surfactant solution to form a mixture, i.e., a crude emulsion; 4) subjecting the crude emulsion to high-pressure dispersion to prepare a nanoparticle emulsion; and 5) removing solvent and water from the emulsion to prepare nanoparticles; wherein the crude emulsion is extruded at an extrusion pressure of 500–2000 bar. The biodegradable polymer is dispersed under high pressure by force, and is selected from one or more of the group consisting of polylactic acid, polycaprolactone, its derivatives and copolymers, and the surfactant is selected from one or more of the group consisting of polyvinyl alcohol, methylcellulose, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, poloxamer 188, poloxamer 123 and poloxamer 407.
[0038] According to one embodiment of the present invention, after step 5), a further step of mixing the nanoparticles with a biocompatible carrier or water for injection may be included.
[0039] On the other hand, descriptions of technical features that are repeated in the components of the preparation method with the nanoparticle and polymer filler composition are omitted.
[0040] The present invention will be described in more detail below through embodiments. The present invention will be described in detail below with reference to preferred embodiments to enable those skilled in the art to readily implement the present invention. These embodiments are only used to illustrate the present invention more specifically, and the scope of the present invention is not limited to these embodiments.
[0041]
Example 1
[0042]
Example 2
[0043]
Example 3
[0044]
Example 4
[0045]
Example 5
[0046]
Example 6
[0047]
Example 7
[0048]
Example 8
[0049]
Example 9
[0050]
Comparative Example 1
[0051]
Experiment Example 1
[0052] Table 1
[0053]
Experiment Example 2
[0054] Table 2
[0055]
Experiment Example 3
[0056] Table 3
[0057]
Experiment Example 4
[0058] Table 4
[0059] Table 5
[0060]
Experiment Example 5
[0061] Table 6
[0062]
Experiment Example 6
[0063] Table 7
[0064]
Experiment Example 7
[0065] Table 8
[0066] As described above, although the present invention has been illustrated through the above embodiments, the present invention is not limited thereto. Various modifications can be made without departing from the scope and spirit of the present invention. Therefore, the scope of protection of the present invention should be interpreted to include all embodiments falling within the scope of the appended claims.
Claims
1. A polymer filler composition comprising biodegradable polymer nanoparticles, The nanoparticles are spherical in shape. The nanoparticles have a particle size of 50–1000 nm. The number-average molecular weight (Mn) of the biodegradable polymer is 10,000–100,000 g / mol. The content of nanoparticles is 10-50% by weight, based on 100% by weight of the polymer filler composition. The biodegradable polymer is selected from one or more of the group consisting of polylactic acid, polycaprolactone, its derivatives, and its copolymers.
2. The polymer filler composition according to claim 1, wherein, The polymer filler composition also includes a biocompatible carrier.
3. The polymer filler composition according to claim 2, wherein, The biocompatible carrier is selected from one or more of the following groups: polyethylene glycol, carboxymethyl cellulose, hyaluronic acid, dextran, collagen, and glycerol.
4. The polymer filler composition according to claim 2, wherein, The content of the biocompatible carrier is 50-90% by weight, based on 100% by weight of the polymer filler composition.
5. The polymer filler composition according to claim 1, wherein, The polymer filler composition further comprises one or more selected from the group consisting of buffers, preservatives, isotonic agents, antioxidants, emulsifiers and wetting agents.
6. The polymer filler composition according to claim 1, wherein, The polymer filler composition is an injectable dosage form for individual administration using a 27-32G injection needle.
7. The polymer filler composition according to claim 1, wherein, The injection rate of the polymer filler composition is 5–15 mm / min.
8. The polymer filler composition according to claim 1, wherein, The polymer filler composition is used for one or more soft tissues selected from the group consisting of the face, neck, chest, buttocks, arms, armpits, hands, legs, and feet.
9. The polymer filler composition according to claim 1, wherein, The polymer filler composition is used for the repair of skin tissue.
10. The polymer filler composition according to claim 1, wherein, The polymer filler composition is used to improve skin wrinkles and reduce tissue volume.
11. The polymer filler composition according to claim 1, wherein, The polymer filler composition is used to treat wounds or stretch marks.
12. A method for preparing a polymer filler composition, comprising the following steps: 1) The step of dissolving a biodegradable polymer in an organic solvent to form a polymer solution; 2) The steps for preparing an aqueous solution of the surfactant; 3) The step of adding the polymer solution to the surfactant aqueous solution to form a mixture, i.e., a crude emulsion; 4) The step of high-pressure dispersion of the original emulsion to prepare nanoparticle emulsion; as well as 5) The step of removing solvent and water from the emulsion to prepare nanoparticles; The original emulsion is dispersed under high pressure at an extrusion pressure of 500–2000 bar. The biodegradable polymer is selected from one or more of the group consisting of polylactic acid, polycaprolactone, its derivatives, and copolymers thereof. The surfactant is selected from one or more of the group consisting of polyvinyl alcohol, methylcellulose, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, poloxamer 188, poloxamer 123 and poloxamer 407.
13. The method for preparing the polymer filler composition according to claim 12, It also includes mixing the nanoparticles with a biocompatible carrier or water for injection after step 5).
14. The method for preparing the polymer filler composition according to claim 13, wherein, The biocompatible carrier is selected from one or more of the following groups: polyethylene glycol, carboxymethyl cellulose, hyaluronic acid, dextran, collagen, and glycerol.
15. The method for preparing the polymer filler composition according to claim 13, wherein, The content of the biocompatible carrier is 50-90% by weight, based on 100% by weight of the polymer filler composition.
16. The method for preparing the polymer filler composition according to claim 12, wherein, The nanoparticles are spherical in shape.
17. The method for preparing the polymer filler composition according to claim 12, wherein, The nanoparticles have a particle size of 50–1000 nm.
18. The method for preparing the polymer filler composition according to claim 12, wherein, The number-average molecular weight (Mn) of the biodegradable polymer is 10,000 to 100,000 g / mol.
19. The method for preparing the polymer filler composition according to claim 12, wherein, The content of nanoparticles is 10-50% by weight, based on 100% by weight of the polymer filler composition.