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KR-20260065558-A - Biodegradable Composite Structure with Uniform Porosity for Tissue Restoration

KR20260065558AKR 20260065558 AKR20260065558 AKR 20260065558AKR-20260065558-A

Abstract

The present invention provides a biodegradable composition for tissue restoration comprising microspheres containing poly-L-lactic acid (PLLA) and hydroxyapatite (HAp). The present invention also provides a method for preparing a biodegradable composition for tissue restoration, comprising the steps of: preparing microspheres by mixing poly-L-lactic acid and hydroxyapatite; and adding hyaluronic acid to the microspheres, wherein the collagen tissue regeneration effect is maintained from the early to the late stages of filler injection.

Inventors

  • 심규식
  • 조한샘
  • 배병기

Assignees

  • 주식회사 플코스킨

Dates

Publication Date
20260508
Application Date
20251030
Priority Date
20241031

Claims (17)

  1. A biodegradable composition for tissue restoration comprising microspheres containing poly-L-lactic acid (PLLA) and hydroxyapatite (HAp).
  2. In Article 1, A biodegradable composition for tissue restoration in which a polynucleotide (PN) is bonded to the surface of the above-mentioned hydroxyapatite.
  3. In Article 2, A biodegradable composition for tissue restoration, wherein the weight ratio (HAp:PN) of the hydroxyapatite and polynucleotide is 4:1 to 6:1.
  4. In Article 1 or Article 2, A biodegradable composition for tissue restoration that further comprises bioactive molecules.
  5. In Article 4, A biodegradable composition for tissue restoration, wherein the above-mentioned bioactive molecule is one or more selected from the group consisting of EVs, polynucleotides, growth factors, and PDRN.
  6. In Article 1, The above composition is a biodegradable composition for tissue restoration intended for injection into the skin.
  7. A filler comprising a biodegradable composition for tissue restoration according to any one of claims 1 to 6.
  8. A biomaterial for cosmetics, diet health foods, biomedical materials, medical materials, or nanocomposite materials comprising a biodegradable composition for tissue restoration according to any one of claims 1 to 6.
  9. A step of preparing microspheres by mixing poly-L-lactic acid and hydroxyapatite; and A method for preparing a biodegradable composition for tissue restoration, comprising the step of adding hyaluronic acid to the microspheres.
  10. In Article 9, A method for preparing a biodegradable composition for tissue restoration, further comprising the step of adding a bioactive molecule to the microspheres.
  11. In Article 10, A method for preparing a biodegradable composition for tissue restoration, wherein the above-mentioned bioactive molecule is one or more of EVs, polynucleotides, growth factors, and PDRN.
  12. In Article 9, A method for preparing a biodegradable composition for tissue restoration, further comprising the step of adding an auxiliary agent to the microspheres.
  13. In Article 12, A method for preparing a biodegradable composition for tissue restoration, wherein the above-mentioned adjuvant is one or more of trehalose, CNC, PVA, and PEG.
  14. Microspheres for tissue restoration manufactured by the manufacturing method of any one of claims 9 to 13.
  15. A pharmaceutical composition for tissue restoration comprising polynucleotide (PN), poly-L-lactic acid, and hydroxyapatite as active ingredients.
  16. In Article 15, The above pharmaceutical composition is a pharmaceutical composition for tissue restoration that further comprises one or more of EVs, polynucleotides, growth factors, PDRN, trehalose, CNC, PVA, and PEG.
  17. In Article 15, A pharmaceutical composition for tissue restoration, wherein the weight ratio (HAp:PN) of the hydroxyapatite and polynucleotide is 4:1 to 6:1.

Description

Biodegradable Composite Structure with Uniform Porosity for Tissue Restoration The present invention relates to a biodegradable composition for tissue restoration comprising microspheres composed of poly-L-lactic acid (PLLA) and hydroxyapatite (HAp). More specifically, the microspheres are a biodegradable composite structure for tissue restoration having uniform porosity, which can maintain the collagen tissue regeneration effect from the early stages of filler injection to the later stages. Fillers are used in cosmetic and reconstructive medicine to fill wrinkles, increase volume, and improve the appearance of the skin. Existing filler technologies include natural low- and high-molecular-weight fillers, calcium-based fillers, and synthetic polymer-based fillers. While natural low- and high-molecular-weight fillers utilize naturally derived ingredients, they have issues such as causing allergic reactions or low durability due to rapid biodegradation. Calcium-based fillers last longer but often cause stiffness at the injection site, while synthetic polymer-based fillers pose risks of inflammatory reactions and side effects, and are difficult to see effects in the early stages. To address these problems, the inventors have made diligent efforts to develop a new type of filler that is sustainable, effective from the initial stages to the mid-to-long term, minimizes pain, and reduces inflammatory responses. The effect of the filler has been maximized by using a combination of various biocompatible materials, and this composite filler provides immediate effects after initial injection and can maintain stable effects over the long term. The composite filler of the present invention is expected to significantly improve patient satisfaction in the fields of cosmetic and reconstructive medicine and set a new standard in the filler market. Throughout this specification, numerous papers and patent documents are referenced and cited. The disclosures of the cited papers and patent documents are incorporated by reference into this specification in their entirety to more clearly explain the state of the art to which the present invention pertains and the content of the present invention. Figure 1 is a scanning electron microscope (SEM) image of the HAp/PLLA microsphere (HAp/PLLA MS) of the present invention. Figure 2 shows the results of infrared spectral (FT-IR) analysis of the HAp-PN complex. Figure 3 is a scanning electron microscope (SEM) image of a PN/HAp/PLLA microsphere (PN/HAp/PLLA MS). Figure 4 shows the PN emission curve of a PN/HAp/PLLA microsphere (PN/HAp/PLLA MS). Figure 5 is a graph showing the results of the cell proliferation evaluation of PN/HAp/PLLA microspheres (PN/HAp/PLLA MS). The present invention will be described in more detail below through examples. These examples are intended solely to explain the present invention more specifically, and it will be obvious to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the invention. Preparation Example 1. Preparation of HAp/PLLA Microspheres and SEM Imaging To obtain PLLA microparticles with uniform porosity, poly-L-lactic acid (PLLA) with a molecular weight of 50,000 g/mol, hydroxyapatite (Hap) with a size of 50 to 100 nm, an aqueous solution of 0.5 wt% polyvinyl alcohol (PVA), an aqueous solution of 10 wt% ammonium bicarbonate (AB), and dichloromethane (DCM) were prepared. Poly-L-lactic acid was dissolved in a mixed solvent at 10 wt%, and then hydroxyapatite was added to the poly-L-lactic acid solution in ratios of 10:1, 4:1, and 2:1, respectively. Afterward, a 10 wt% aqueous solution of ammonium bicarbonate and a 0.5 wt% aqueous solution of polyvinyl alcohol were added and mixed homogeneously. Subsequently, the mixed solution was stirred for about a day to evaporate the organic solvent, and then the ammonium bicarbonate was removed by washing with sterile distilled water at 40°C to fabricate pores. Preparation Example 2. Preparation of PN-linked HAp In order to confirm the suitable binding conditions of HAp and PN in the HAp/PLLA composite prepared in Preparation Example 1 above by dissolving poly-L-lactic acid in a mixed solvent at 10 wt% and then adding hydroxyapatite to the solution at a weight ratio of 2:1, the binding yield was determined by varying the ratio of HAp to PN. A 1% (w/v) PN solution was prepared using 0.1 M MES buffer, and HAp was also appropriately dispersed by adding 20, 60, and 100 mg, respectively, to 18 mL of 0.1 M MES buffer. After adding 2 mL of the PN solution to the HAp dispersion, the reaction was carried out at 4°C for 1 day. At this time, the weight ratios of HAp to PN were 1:1, 3:1, and 5:1, respectively. After the reaction was finished, the mixture was centrifuged at 3500 rpm for 15 minutes at 4°C, and the HAp/PLLA that settled at the bottom was lightly washed with sterile water, centrifuged to obtain the product, and then freeze-dried. Preparation