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WO2017065429A1 - Composition injectable pour la régénération de tissu cutané ou l'augmentation de volume de tissu cutané comprenant des microsphères poreuses creuses - Google Patents

Composition injectable pour la régénération de tissu cutané ou l'augmentation de volume de tissu cutané comprenant des microsphères poreuses creuses Download PDF

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Publication number
WO2017065429A1
WO2017065429A1 PCT/KR2016/010857 KR2016010857W WO2017065429A1 WO 2017065429 A1 WO2017065429 A1 WO 2017065429A1 KR 2016010857 W KR2016010857 W KR 2016010857W WO 2017065429 A1 WO2017065429 A1 WO 2017065429A1
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Prior art keywords
skin tissue
composition
hollow porous
porous microspheres
injection
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Ceased
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PCT/KR2016/010857
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English (en)
Korean (ko)
Inventor
김혁
아영창
최성욱
문승관
박원석
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Amorepacific Corp
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Amorepacific Corp
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Priority to JP2018516478A priority Critical patent/JP6605722B2/ja
Priority to CN201680060085.XA priority patent/CN108135808A/zh
Publication of WO2017065429A1 publication Critical patent/WO2017065429A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/31—Hydrocarbons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations

Definitions

  • the present invention relates to a composition for injection of skin tissue regeneration or skin tissue volume enhancement to improve skin wrinkles and depressions.
  • Filler (filler) of the medical devices for cosmetic surgery sold for the purpose of cosmetic surgery is used to inject into the skin tissue wrinkles and depressions.
  • fillers are injected into the skin tissue to improve skin wrinkles or depressions in such a way as to increase the volume of the skin tissue through the volume of the material itself.
  • the most commonly used fillers include intangible substances in the form of gels such as hyaluronic acid and collagen, but have a problem that their cosmetic treatment effects are not maintained for a long time as they are absorbed into skin tissues over time.
  • porous material which is a filler component, developed in the past, is not possible to be implanted into the skin tissue through injection because it is several tens of mm in size. There was a drawback to be implanted into the skin tissue only through surgery to cut the skin tissue.
  • An object of the present invention is to inject a porous microspheres into the skin tissue through injection, and to increase the volume of skin tissue by proliferating the cells in the porous microspheres skin tissue regeneration or skin tissue volume injection composition for injection To provide.
  • an aspect of the present invention is a cavity formed in the center; And it provides a composition for skin tissue regeneration or skin tissue volume enhancement injection comprising a hollow porous microspheres comprising a partition including a micropores surrounding the cavity.
  • the hollow porous microspheres included in the composition according to the present invention have a small particle size, thereby solving the disadvantage that the existing porous materials had to be implanted by cutting the skin tissue due to the large particle size.
  • the hollow porous microspheres have a dual structure including a bulkhead and a microcavity formed in the center of the particle, skin tissue cells in vivo easily move into the hollow porous microspheres using the micropores as a channel. And the migrated skin tissue cells can effectively proliferate within the cavity. Furthermore, the hollow porous microspheres according to the present invention can be applied to the pharmaceutical industry such as bone tissue regeneration as well as improvement of skin wrinkles or depressions through skin tissue regeneration.
  • the newly expanded skin tissue cells maintain their volume, thereby increasing the skin tissue volume enhancing effect as well as improving the safety. I can keep it for a long time.
  • FIG. 1 is a view showing an electron scanning micrograph of the particle surface and fragments according to the type and content of porogen in the production of hollow porous microspheres according to an embodiment of the present invention.
  • Figure 2 is a diagram showing a live / dead staining confocal micrograph of cultured fibroblasts in hollow porous microspheres according to an embodiment of the present invention.
  • Figure 3 is a diagram showing the cell growth rate through MTT assay after culturing fibroblasts in hollow porous microspheres according to an embodiment of the present invention.
  • Figure 4 is a view showing the effect of cell migration and tissue regeneration into the porous microspheres after implanting the hollow porous microspheres in the mouse skin according to an embodiment of the present invention.
  • FIG. 5 is a view showing a change in the shape of the porous microspheres before and after the scanning performance measurement of the hollow porous microspheres according to an embodiment of the present invention using a tensile force meter.
  • skin refers to an organ that covers the exterior of an organism and is composed of the epidermis, dermis and subcutaneous fat layer and includes the scalp and hair as well as tissues covering the outside of the face or the entire body. to be.
  • fillers refers to fillers, reinforcing agents, and the like, which are injected into the body, including all materials injected for cosmetic, shaping, and strengthening the epidermis, dermis, or subcutaneous fat layer or joint of the skin. It is the meaning of righteousness.
  • Average diameter in the present specification means a value obtained by averaging the diameter that is a line segment connecting both ends of the cross section of the object, for example, in the case of the cavity of the present invention when the cavity formed in the hollow porous microspheres is not a sphere It may mean the average value of the diameter of the cavity itself. Or it may mean an average value of the diameter of each cavity present in the plurality of microspheres. In the case of micropores, when the micropores themselves are not spherical, they may mean an average value of diameters of the micropores themselves or an average value of diameters of the plurality of micropores.
  • One embodiment of the invention the cavity formed in the center; And a hollow porous microsphere including a partition including micropores surrounding the cavity, thereby providing a composition for skin tissue regeneration or skin tissue volume injection.
  • Another embodiment of the present invention is an injection method for skin tissue regeneration or skin tissue volume enhancement, the method comprising the step of administering an effective amount of a composition comprising a hollow porous microspheres to a subject, the hollow porous The microspheres may provide a partition including a cavity formed in the center and micropores surrounding the cavity.
  • the hollow porous microspheres are a cavity formed in the center and micropores surrounding the cavity It may be provided to include a partition including a.
  • Another embodiment of the present invention is a hollow porous microspheres for use in skin tissue regeneration or skin tissue volume injection, wherein the hollow porous microspheres comprise a cavity formed in the center and micropores surrounding the cavity It may provide to include.
  • the cavity formed in the center of the hollow porous microspheres may have an average diameter of 5 to 150 ⁇ m. If the diameter of the cavity is less than 5 ⁇ m difficult growth of cells, if the diameter of more than 150 ⁇ m microspheres are too weak to be destroyed during in vivo injection.
  • the average diameter of the cavity is 5 ⁇ m or more, 10 ⁇ m or more, 13 ⁇ m or more, 15 ⁇ m or more, 17 ⁇ m or more, 20 ⁇ m or more, 23 ⁇ m or more, 25 ⁇ m or more, 27 ⁇ m or more, 30 ⁇ m or more, 33 At least 35 ⁇ m, at least 35 ⁇ m, at least 37 ⁇ m, at least 40 ⁇ m, at least 43 ⁇ m, at least 45 ⁇ m, at least 48 ⁇ m, at least 50 ⁇ m, at least 60 ⁇ m, at least 70 ⁇ m, at least 80 ⁇ m, at least 90 ⁇ m, at least 100 ⁇ m.
  • the average diameter of the cavity is 150 ⁇ m or less, 140 ⁇ m or less, 130 ⁇ m or less, 120 ⁇ m or less, 110 ⁇ m or less, 100 ⁇ m or less, 90 ⁇ m or less, 80 ⁇ m or less, 70 ⁇ m or less, 60 ⁇ m or less, 50 ⁇ m 47 ⁇ m or less, 45 ⁇ m or less, 43 ⁇ m or less, 40 ⁇ m or less, 37 ⁇ m or less, 35 ⁇ m or less, 33 ⁇ m or less, 30 ⁇ m or less, 28 ⁇ m or less, 25 ⁇ m or less, 23 ⁇ m or less, 20 ⁇ m or less, It may be 18 ⁇ m or less, 15 ⁇ m or less, 13 ⁇ m or less, 10 ⁇ m or less, or 5 ⁇ m, but any size may be included without limitation if the skin tissue cells
  • the particles of the hollow porous microspheres included in the composition according to the present invention may have an average diameter of 50 to 200 ⁇ m, it is possible to inject into the skin tissue through injection, the proliferation of skin tissue cells If possible, all of the above ranges may be included.
  • the hollow porous microspheres may be administered through a needle having an inner diameter of 300 ⁇ m or less in the skin tissue by having a small particle size in the above range, and the existing porous materials may be administered due to the large particle size. You can resolve the shortcomings that had to be implanted by incision. When the diameter of the hollow porous microspheres is less than 50 ⁇ m, it is difficult to proliferate the skin tissue cells.
  • the average diameter of the hollow porous microsphere particles is 50 ⁇ m or more, 60 ⁇ m or more, 70 ⁇ m or more, 80 ⁇ m or more, 90 ⁇ m or more, 100 ⁇ m or more, 110 ⁇ m or more, 120 ⁇ m or more, 130 ⁇ m or more, 140 Or at least 150 ⁇ m, at least 160 ⁇ m, at least 160 ⁇ m, at least 170 ⁇ m, at least 180 ⁇ m, at least 190 ⁇ m, or at least 200 ⁇ m.
  • the average diameter of the hollow porous microsphere particles is 200 ⁇ m or less, 190 ⁇ m or less, 180 ⁇ m or less, 170 ⁇ m or less, 160 ⁇ m or less, 150 ⁇ m or less, 140 ⁇ m or less, 130 ⁇ m or less, 120 ⁇ m or less, 110 ⁇ m Up to 100 ⁇ m, up to 90 ⁇ m, up to 80 ⁇ m, up to 70 ⁇ m, up to 60 ⁇ m or up to 50 ⁇ m.
  • the volume of the hollow porous microspheres may be 20 to 80% by volume relative to the total volume of the hollow porous microspheres. If less than 20% by volume, there is not enough space for the skin tissue cells to proliferate. If the volume is greater than 80% by volume, the thickness of the partition wall becomes too thin, so that the shape of the microspheres may be maintained without collapse. In one embodiment, the thickness of the partition wall may be 1/5 to 1/2 of the total diameter of the hollow porous microspheres.
  • the micropores included in the partition wall of the hollow porous microspheres may have an average diameter of 5 to 50 ⁇ m as an embodiment.
  • the hollow porous microspheres are less than 5 ⁇ m, the skin tissue cells cannot migrate into the microspheres when the hollow porous microspheres are injected into the subcutaneous tissue.
  • the preferred porosity of the hollow porous microspheres may be an average of 20 to 80%.
  • the hollow porous microspheres according to an embodiment of the present invention may include a hydrophobic biodegradable polymer as an embodiment.
  • the hydrophobic biodegradable polymer is polylactic acid (poly-L-Lactic Acid, PLLA), polyglycolic acid (polyglycolic acid, PGA), polylactic acid-glycolic acid copolymer (poly (lactic-co-glycolic acid), PLGA ), Poly- ⁇ - (caprolactone) (Polycaprolactone, PCL), polyanhydrides, polyorthoesters, polyviniyalcohols, polyethyleneglycols, polyurethanes, Polyacrylic acid, poly-N-isopropyl acrylamide, poly (ethylene oxide) -poly (propylene oxide) -poly (ethylene oxide) copolymer-poly propylene oxide-polyethylene oxide copolymer), copolymers thereof, and mixtures thereof, but may be safe and degradable when injected into skin
  • the cavity and the micropores of the hollow porous microspheres are formed by a pore-forming substance, that is, porogen, and the porogen is incompatible with the hydrophobic biodegradable polymer.
  • a pore-forming substance that is, porogen
  • the porogen is incompatible with the hydrophobic biodegradable polymer.
  • any hydrophobic fluid having a density lower than that of water may be included without limitation.
  • the cavity and micro-pore forming material may be a material having a boiling point at 250 ° C. or less at 1 atm, and may be a liquid material at 30 to 150 ° C. at 1 atm.
  • the cavity and micropore-forming substance may be at least one selected from the group consisting of alkanes, vegetable oils, and mixtures thereof.
  • the alkanes are at least one selected from the group consisting of Octane, Undecane, Tridecane, Pentadecane, and mixtures thereof.
  • the present invention may form pores by applying other materials in addition to the specific materials, in one embodiment, the present invention is hollow and according to the concentration and type of porogen forming pores in the production of the hollow porous microspheres The size and shape of the micropores can be controlled, and the pore uniformity can also be increased.
  • the skin tissue regeneration or skin tissue volume enhancement in the composition of the present invention as an embodiment skin tissue cells in vivo is moved through the micropores into the hollow porous microspheres, the central The migrated skin tissue cells in the cavity may include proliferation to regenerate skin tissue or to enhance volume. That is, cells existing in the living tissue may penetrate into the hollow porous microspheres and grow and divide to form new living tissue.
  • the size and shape of the micropores of the cavity and the partition wall formed in the center of the microsphere can be freely adjusted, and the hollow porous microspheres Fibroblasts, adipocytes, etc., which are present outside, penetrate into the porous microspheres, and may provide a space for growth and division.
  • the size of the hollow porous microspheres and the micropores of the cavity and the partition wall formed at the center may be controlled and manufactured by using a microfluidic device or a membrane emulsion device.
  • the size of the microspheres can be constantly controlled by adjusting the speed of injecting the discontinuous phase through the microconduit into the conduit for transporting the continuous phase.
  • the discontinuous phase may be controlled to be transferred to a conduit through which a continuous phase flows through a membrane having a constant pore size instead of a microconduit used in a microfluidic device.
  • the composition may be for improving skin wrinkles or skin depressions. More specifically, the composition may be used for the purpose of improving aging including skin wrinkles, improving skin tone or filler or lifting for improving skin elasticity, and the like, but are not limited thereto. Can be. For example, it may be used for artificial skin, artificial cartilage, bone filler, molded prosthesis, and the like. Alternatively, the composition according to the present invention may be provided as a pharmaceutical or cosmetic composition as an example.
  • the composition for skin tissue regeneration or skin tissue volume injection according to the present invention may comprise the hollow porous microspheres 1 to 50% by weight relative to the total weight of the composition. If the content is less than 1% by weight, the hollow porous microspheres content is too small, so it is difficult to expect a desired effect when injected into the skin tissue. If the content is more than 50% by weight, the injection into the skin tissue cannot be smoothly injected. More specifically, the composition for skin tissue regeneration or skin tissue volume injection according to the present invention may include the hollow porous microspheres in an amount of 5 to 20% by weight based on the total weight of the composition.
  • the composition may include a water-soluble polymer to improve the viscosity and stability of the composition including the porous microspheres in addition to the hollow porous microspheres.
  • the water-soluble polymer is alginic acid, hyaluronic acid, carboxymethyl cellulose, dextran, collagen, and their degradation products, gelatin. It may further comprise one or more compounds selected from the group consisting of elastin.
  • Hollow porous microspheres according to an embodiment of the present invention were prepared by the following method.
  • Step 1 Simple Fluid Device fluidic device
  • a 30-gauge needle turned at 90 ° to a PVC tube was inserted, and a micro glass tube was inserted between the needle and the PVC tube to prepare a microfluidic device.
  • the fabricated microfluidic device was filled with a fine gap using an epoxy adhesive.
  • Step 2 Alkanes included PLLA Preparation of the solution
  • PLLA PLLA
  • ReOMER LR 704S Evonik Industries AG
  • dichloromethane 34355-0350, Junsei
  • 0.1, 0.3 g and 0.6 g of undecane Undecane, U407, Sigma-aldrich
  • Tridecane Tridecane, T57401, Sigma-aldrich
  • pentadecane pentadecane, 76510, Sigma-aldrich
  • Step 3 Uniform PLLA emulsion Produce
  • the PLLA solution obtained in step 2 was a continuous phase of 2% PVA solution, the flow rate was 1.5 ml per minute, and the PLLA solution containing alkanes was discontinuous phase. Using a 30-gauge syringe needle, the flow rate was 0.1 ml per minute to form an emulsion of a constant size.
  • the emulsion obtained in step 3 was dispersed in a 2% PVA collection phase and stirred at 150 rpm, and then dichloromethane was sufficiently volatilized.
  • Step 5 remove porosity inducing substance to impart porosity
  • the PLLA beads obtained in step 4 were washed several times with distilled water (D.W.), and then sublimated alkanes using a lyophilizer to prepare porous PLLA beads, hollow porous microspheres of uniform size.
  • FIG. 1 Each hollow porous microspheres prepared above are shown in FIG. 1. It can be seen that the cavity is more effectively produced in the center of the microspheres as the content of the pore-forming substance is increased or as the length of the hydrocarbon chain is increased.
  • Hollow porous microspheres according to an embodiment of the present invention were prepared by the following method.
  • Step 1 Simple Fluid Device fluidic device
  • a 30-gauge needle turned at 90 ° to a PVC tube was inserted, and a micro glass tube was inserted between the needle and the PVC tube to prepare a microfluidic device.
  • the fabricated microfluidic device was filled with a fine gap using an epoxy adhesive.
  • Step 2 containing vegetable oil PLLA Preparation of the solution
  • Step 3 Uniform PLLA emulsion Produce
  • the PLLA solution obtained in step 2 is a continuous phase of 2% PVA solution, the flow rate is 1.5 ml per minute, and the PLLA solution containing vegetable oil is discontinuous phase.
  • the flow rate was 0.1 ml per minute to form an emulsion of a constant size.
  • Step 4 Uniform PLLA Bead Produce
  • the emulsion obtained in step 3 was dispersed in a 2% PVA collection phase and stirred at 150 rpm, and then dichloromethane was sufficiently volatilized.
  • Step 5 Remove porosity inducing substance to impart porosity
  • Step 4 After washing several times the beads PLLA obtained in Step 4 in distilled water (DW), was prepared in a freeze-porous PLLA bead removing the vegetable oil using a dryer to a hollow porous microspheres having a uniform size.
  • DW distilled water
  • a water-soluble polymer such as hyaluronic acid (hyaluronic acid), carboxymethyl cellulose (mixture) for improving the viscosity and stability of the composition comprising the hollow porous microspheres and the porous microspheres Injectable compositions were prepared.
  • each composition is as shown in Table 1 and Table 2, together with the injection pressure measurement results of the composition for injection containing the hollow porous microspheres according to the content of each composition.
  • Example 1 70% ethanol was used as the porous pores (small pores: Tridecane 3wt%) and the hollow pores (large pores: aldecane containing 6wt% tridecane as the alkanes) of Example 1, respectively.
  • the cells were sufficiently washed with PBS, and NIH3T3 fibroblasts were transplanted to observe cell proliferation behavior.
  • the NIH3T3 fibroblasts were dispersed in culture medium at a concentration of 1 ⁇ 10 3 cells / mL, stirred for 6 hours using a spinner flask, and the porous particles were transferred to a culture plate and cultured.
  • Example 1 70% ethanol was used as the porous pores (small pores: Tridecane 3wt%) and the hollow pores (large pores: aldecane containing 6wt% tridecane as the alkanes) of Example 1, respectively. Sterilized. This was sufficiently washed with PBS to inject the porous PLLA particles dispersed in PBS using 23 gauge needles subcutaneously in nude mice, and observed the cell infiltration and cell proliferation in the porous microspheres over 8 weeks. After injecting the porous microspheres, the skin and subcutaneous particles of nude mice were cut at 2, 4, 6, and 8 weeks, respectively, and fixed in 4% formaldehyde for 3 hours, and then the tissue was placed in a 30% saccharose solution.
  • cryo sections were prepared in a 20 ⁇ m size through a cryo microtome.
  • the frozen sections were attached to the slide glass and dried on a 50 ° C. heating block for 3 hours to allow the tissue to adhere well to the slide glass.
  • the tissue sections were H & E stained to observe the tissue reaction around the porous PLLA microspheres.
  • porous pores (small pores) containing only micropores without hollows are mostly present outside the cells until 8 weeks, but hollow pores containing hollows are Cells penetrate into the particles and induce new tissue formation.
  • the particles did not completely decompose even after 8 weeks, confirming the possibility of long-term maintenance of the porous microspheres in vivo.
  • a performance test was conducted to determine the possibility of injection injection of the compositions prepared in Tables 1 and 2. Scanning performance was measured with the tensile force meter set to the compressive strength measurement mode. After removing the cap of the syringe containing the composition containing each hollow porous microspheres and mounting a needle having a specification of 23G, the syringe was fixed vertically to the needle measuring plate downwards. The tension force meter was operated to push the plunge mounted on the syringe at a rate of 1 mm / sec, and the force following compression was measured until the contents contained in the pores were completely emptied.
  • Shapes of the hollow porous microspheres were collected by collecting samples before and after the injection performance test for Preparation Example 6 of Table 1 in order to confirm the change in shape after injection injection of the composition including the hollow porous microspheres according to the embodiment of the present invention. Changes were observed through a 3D measuring laser microscope (Olympus). The results are shown in FIG. As shown in FIG. 5, in the case of Preparation Example 6, it was confirmed that despite the high injection pressure, the shape of the porous microspheres was well maintained as compared with before the injection.
  • the present invention can provide the following embodiments as an example.
  • the first embodiment includes a cavity formed in the center; And a hollow porous microsphere including a partition including micropores surrounding the cavity, thereby providing a composition for skin tissue regeneration or skin tissue volume injection.
  • 2nd Embodiment can provide the composition for skin tissue regeneration or skin tissue volume promotion injections in 1st Embodiment whose average diameter of the cavity of the said hollow porous microsphere is 5-150 micrometers.
  • the third embodiment provides the composition for skin tissue regeneration or skin tissue volume enhancement injection according to any one of the first and second embodiments, wherein the hollow porous microspheres have an average diameter of 50 to 200 ⁇ m. can do.
  • the fourth embodiment is a skin tissue regeneration of any one of the first to third embodiments, wherein the volume of the hollow porous microspheres is 20 to 80% by volume relative to the total volume of the hollow porous microspheres.
  • skin tissue volume enhancing injectable compositions may be provided.
  • the composition for injecting skin tissue regeneration or skin tissue volume enhancement in any one or more of the first to fourth embodiments has an average diameter of the micropores of the hollow porous microspheres of 5 to 50 ⁇ m. Can provide.
  • the sixth embodiment can provide a composition for injection of skin tissue regeneration or skin tissue volume enhancement in any one or more of the first to fifth embodiments, wherein the porosity of the hollow porous microspheres is on average 20 to 80%. Can be.
  • the hollow porous microspheres may include a composition for injection of skin tissue regeneration or skin tissue volume enhancement, comprising a hydrophobic biodegradable polymer. have.
  • the hydrophobic biodegradable polymer is polylactic acid (PLL), polyglycolic acid (PGA), polylactic acid-glycolic acid copolymer (poly ( lactic-co-glycolic acid, PLGA), poly- ⁇ - (caprolactone) (Polycaprolactone, PCL), polyanhydrides, polyorthoesters, polyvinthoalcohols, polyviniyalcohols, polyethylene glycols ( polyethyleneglycol, polyurethane, polyacrylic acid, poly-N-isopropyl acrylamide, poly (ethylene oxide) -poly (propylene oxide) -poly (ethylene oxide)
  • a composition for injection of skin tissue regeneration or skin tissue volume enhancement which is at least one selected from the group consisting of copolymers, polypropylene oxide-polyethylene oxide copolymers, copolymers thereof and mixtures thereof. can do.
  • the cavity and micropore-forming inducer of the hollow porous microspheres are incompatible with hydrophobic biodegradable polymers and have a lower density than water.
  • Skin tissue regeneration or skin tissue volume enhancing injectable compositions that are hydrophobic fluids may be provided.
  • the cavity and micropore forming inducing substance is at least one selected from the group consisting of alkanes, vegetable oils, and mixtures thereof, skin tissue regeneration or skin tissue volume enhancement.
  • injectable compositions may be provided.
  • the alkanes are selected from the group consisting of Octane, Undecane, Tridecane, Pentadecane, and mixtures thereof.
  • the vegetable oil is at least one selected from the group consisting of soybean oil, corn oil, cottonseed oil, olive oil, grape seed oil, walnut oil, sesame oil, perilla oil and mixtures thereof. Can provide.
  • the composition may include alginic acid, hyaluronic acid, carboxymethyl cellulose, dextran ( Dextran, collagen (collagen), gelatin (gelatin) and elastin may further provide a composition for injection of skin tissue regeneration or skin tissue volume enhancement further comprising one or more water-soluble polymers selected from the group consisting of.
  • the thirteenth embodiment is any one or more of the first to twelfth embodiments, wherein the composition comprises 1 to 50% by weight of the hollow porous microspheres relative to the total weight of the composition, skin tissue regeneration or skin tissue Volume enhanced injectable compositions may be provided.
  • the skin tissue regeneration or skin tissue volume enhancement is such that in vivo skin tissue cells migrate through the micropores into the hollow porous microspheres. It is possible to provide a composition for skin tissue regeneration or skin tissue volume enhancing injection, wherein the migrated skin tissue cells proliferate in a central cavity to regenerate skin tissue or enhance volume.
  • the fifteenth embodiment can provide a composition for injection of skin tissue regeneration or skin tissue volume enhancement in any one or more of the first to fourteenth embodiments, wherein the composition is for fillers for improving skin wrinkles or skin depressions. .

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Abstract

La présente invention concerne une composition injectable pour la régénération de tissu cutané ou l'augmentation de volume de tissu cutané comprenant des microsphères poreuses creuses comprenant une cavité au centre de celles-ci et une barrière entourant la cavité et comprenant des pores fins. Les microsphères poreuses creuses comprises dans la composition selon la présente invention ont une petite taille de particule et, par conséquent, peuvent être administrées par une injection dans un tissu cutané, et permettent de déplacer des cellules de tissu cutané de façon à proliférer efficacement dans les cavités. Une fois qu'une durée prédéterminée s'est écoulée, les cellules de tissu cutané nouvellement proliférantes maintiennent le volume de celui-ci même après que les microsphères poreuses creuses aient été biologiquement dégradées à l'intérieur de la peau ; ainsi, des effets régénérateurs de tissu cutané peuvent être maintenue de façon sûre pendant une longue durée.
PCT/KR2016/010857 2015-10-14 2016-09-28 Composition injectable pour la régénération de tissu cutané ou l'augmentation de volume de tissu cutané comprenant des microsphères poreuses creuses Ceased WO2017065429A1 (fr)

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