WO2017065429A1 - Injectable composition for skin tissue regeneration or skin tissue volume increase comprising hollow porous microspheres - Google Patents

Abstract

The present invention relates to an injectable composition for skin tissue regeneration or skin tissue volume increase comprising hollow porous microspheres comprising a cavity in the center thereof and a barrier surrounding the cavity and comprising fine pores. The hollow porous microspheres comprised in the composition according to the present invention have a small particle size, thus can be administered by an injection into skin tissue, and allow moving skin tissue cells to effectively proliferate within the cavities. After a predetermined period elapses, the newly proliferated skin tissue cells maintain the volume thereof even after the hollow porous microspheres biodegrade inside skin; thus, skin tissue regenerative effects can be safely maintained for a long time.

Description

Composition for injection of skin tissue regeneration or skin tissue volume enhancement comprising hollow porous microspheres

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.

Most 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. Currently, 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.

In addition, in order to have a wide range of use as a medical device for aesthetic surgery, it must be delivered by injection. The 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.

[Preceding technical literature]

[Patent Documents]

Republic of Korea Patent Publication No. 2011-0075618

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.

In order to solve the above object, 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.

Since 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.

In addition, according to the present invention, even after the hollow porous microspheres are biodegraded in the skin after a certain period of time, 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.

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.

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.

As used herein, the term "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.

As used herein, the term "filler" 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.

Hereinafter, the present invention will be described in detail.

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.

Another embodiment of the present invention is to use for the preparation of the composition for injection of skin tissue regeneration or skin tissue volume enhancement of the hollow porous microspheres, 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.

In one embodiment, the cavity formed in the center of the hollow porous microspheres may have an average diameter of 5 to 150 ㎛. If the diameter of the cavity is less than 5㎛ difficult growth of cells, if the diameter of more than 150㎛ microspheres are too weak to be destroyed during in vivo injection. Specifically, the average diameter of the cavity is 5 μm or more, 10 μm or more, 13 μm or more, 15 μm or more, 17 μm or more, 20 μm or more, 23 μm or more, 25 μm or more, 27 μm or more, 30 μm or more, 33 At least 35 μm, at least 35 μm, at least 37 μm, at least 40 μm, at least 43 μm, at least 45 μm, at least 48 μm, at least 50 μm, at least 60 μm, at least 70 μm, at least 80 μm, at least 90 μm, at least 100 μm. , 110 μm or more, 120 μm or more, 130 μm or more, 140 μm or more, or 150 μm. In addition, the average diameter of the cavity is 150 µm or less, 140 µm or less, 130 µm or less, 120 µm or less, 110 µm or less, 100 µm or less, 90 µm or less, 80 µm or less, 70 µm or less, 60 µm or less, 50 µm 47 µm or less, 45 µm or less, 43 µm or less, 40 µm or less, 37 µm or less, 35 µm or less, 33 µm or less, 30 µm or less, 28 µm or less, 25 µm or less, 23 µm or less, 20 µm or less, It may be 18 μm or less, 15 μm or less, 13 μm or less, 10 μm or less, or 5 μm, but any size may be included without limitation if the skin tissue cells proliferate.

In one embodiment, 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㎛, 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 μm 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 μm, it is difficult to proliferate the skin tissue cells. When the diameter of the hollow porous microspheres is more than 200 μm, the porous microspheres are not easily implanted using the needle in the skin tissue. Specifically, the average diameter of the hollow porous microsphere particles is 50 μm or more, 60 μm or more, 70 μm or more, 80 μm or more, 90 μm or more, 100 μm or more, 110 μm or more, 120 μm or more, 130 μm or more, 140 Or at least 150 μm, at least 160 μm, at least 160 μm, at least 170 μm, at least 180 μm, at least 190 μm, or at least 200 μm. In addition, the average diameter of the hollow porous microsphere particles is 200 μm or less, 190 μm or less, 180 μm or less, 170 μm or less, 160 μm or less, 150 μm or less, 140 μm or less, 130 μm or less, 120 μm or less, 110 μm Up to 100 μm, up to 90 μm, up to 80 μm, up to 70 μm, up to 60 μm or up to 50 μm.

In one embodiment, 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.

Specifically, the micropores included in the partition wall of the hollow porous microspheres may have an average diameter of 5 to 50 ㎛ as an embodiment. When the hollow porous microspheres are less than 5 μm, the skin tissue cells cannot migrate into the microspheres when the hollow porous microspheres are injected into the subcutaneous tissue.

For example, 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. Specifically, 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-ε- (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 tissue. One can not be both included.

In addition, according to an embodiment of the present invention, 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. For example, any hydrophobic fluid having a density lower than that of water may be included without limitation. Specifically, 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. For example, the cavity and micropore-forming substance may be at least one selected from the group consisting of alkanes, vegetable oils, and mixtures thereof. In one embodiment the alkanes are at least one selected from the group consisting of Octane, Undecane, Tridecane, Pentadecane, and mixtures thereof. Soybean oil, corn oil, cottonseed oil, olive oil, grapeseed oil, walnut oil, sesame oil, perilla oil 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.

According to one embodiment, 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. According to an embodiment of the present invention, by adjusting the mixing ratio of the pore-forming substance and the hydrophobic biodegradable polymer, 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.

As an example, 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. In the case of the microfluidic 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. In the case of membrane emulsification, 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.

According to an embodiment of the present invention, 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.

In addition, 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.

In one embodiment, 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. In one embodiment, 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.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention, and it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as being limited by these examples.

Example 1 Preparation of Hollow Porous Microspheres 1

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

0.1 g of PLLA (RESOMER LR 704S, Evonik Industries AG) was used as a hydrophobic biodegradable polymer and 10 g of dichloromethane (34355-0350, Junsei). ) Or 0.1, 0.3 g and 0.6 g of undecane (Undecane, U407, Sigma-aldrich) or tridecane (Tridecane, T57401, Sigma-aldrich) or pentadecane (Pentadecane, 76510, Sigma-aldrich), respectively ( 1, 3, 6 wt%) hydrophobic biodegradable polymer (PLLA) solutions were prepared.

Step 3: Uniform PLLA emulsion  Produce

Using the microfluidic device, 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.

Step 4: Uniform Hollow Porous Microsphere  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

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.

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.

Example 2 Preparation of Hollow Porous Microspheres 2

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

0.1 g of PLLA (RESOMER LR 704S, Evonik Industries AG) as a hydrophobic biodegradable polymer, 10 g of dichloromethane (34355-0350, Junsei), and 0.5 g of cottonseed oil or soybean oil as pore-forming substances. The solution was prepared.

Step 3: Uniform PLLA emulsion  Produce

Using the microfluidic device, 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. Using a 30-gauge syringe needle, 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

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.

Example 3 Preparation of Injectable Composition Containing Hollow Porous Microspheres

In one embodiment of the present invention, 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.

At this time, the content of 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.

Ingredient (% by weight)	Preparation Example 1	Preparation Example 2	Preparation Example 3	Preparation Example 4	Preparation Example 5	Preparation Example 6	Comparative Production Example 1
Porous Microspheres	1.0	10.0	20.0	30.0	40.0	50.0	60.0
Hyaluronic acid	2.0	2.0	2.0	2.0	2.0	2.0	2.0
Distilled water	97	88	78	68	58	48	38
Scanning performance (N)	3.1	10.9	15.4	21.2	32.7	58.9	fail

Ingredient (% by weight)	Preparation Example 7	Preparation Example 8	Preparation Example 9	Preparation Example 10	Preparation Example 11	Preparation Example 12	Comparative Production Example 2
Porous Microspheres	1.0	10.0	20.0	30.0	40.0	50.0	60.0
Carboxymethylsululose	2.0	2.0	2.0	2.0	2.0	2.0	2.0
Distilled water	97	88	78	68	58	48	38
Scanning performance (N)	7.4	10.5	17.8	26.4	37.9	62.5	fail

Test Example 1 Culture of Skin Tissue Cells

Experiments for comparing the cell mobility and proliferation efficacy according to whether the hollow porous microspheres in accordance with an embodiment of the present invention was formed as follows.

As a comparative example, 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. After sterilization, 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. Cell culture 1, 3, 7, 10 days after the culture of each of the porous microspheres in the live / DEAD staining, cell adhesion and proliferation was confirmed by confocal microscopy and MTT assay. As shown in Figure 2 and 3, the hollow porous pores (large pores) including the hollow NIH3T3 fibroblast penetration into the inner pores as compared to the porous pores (Small pores) containing only the micropores without the hollow and It can be seen that the growth is well up to the 10th day. This means that the hollows contained in the porous microspheres have a great effect on cell penetration and proliferation.

Test Example 2 Evaluation of Cell Mobility and Tissue Regeneration Efficacy of Hollow Porous Microspheres through Animal Experiments

Experiments to compare the cell mobility and tissue regeneration efficacy according to whether the hollow porous microspheres in accordance with an embodiment of the present invention was carried out as follows.

As a comparative example, 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. Immerse for 12 hours. Then, cryo sections were prepared in a 20 μm 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.

As a result, as shown in FIG. 4, 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. In addition, the particles did not completely decompose even after 8 weeks, confirming the possibility of long-term maintenance of the porous microspheres in vivo.

Test Example 3 Measurement of the Injection Performance of a Composition Containing Hollow Porous Microspheres

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.

The results are shown in Tables 1 and 2 above. As shown in Tables 1 and 2, when the porous porous microspheres were dispersed in 2% hyaluronic acid and 2% carboxymethyl cellulose, respectively, and the injection performance was measured, the content of microspheres in the composition was decreased as in Comparative Preparation Examples 1 and 2. If greater than 50% by weight, no injection was possible.

Test Example 4 Comparison of Shapes Before and After Injection Injection of Compositions Containing Hollow Porous Microspheres

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 μm. 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. Or skin tissue volume enhancing injectable compositions may be provided.

In the fifth embodiment, 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 µm. 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.

In a seventh embodiment, in any one or more of the first to sixth embodiments, 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.

In the eighth embodiment, in the seventh embodiment, the hydrophobic biodegradable polymer is polylactic acid (PLL), polyglycolic acid (PGA), polylactic acid-glycolic acid copolymer (poly ( lactic-co-glycolic acid, PLGA), poly-ε- (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) Provided is 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.

In the ninth embodiment, in any one or more of the first to eighth embodiments, 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.

In a tenth embodiment, in the ninth embodiment, 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.

In an eleventh embodiment, in the tenth embodiment, the alkanes are selected from the group consisting of Octane, Undecane, Tridecane, Pentadecane, and mixtures thereof. At least one, wherein 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.

In a twelfth embodiment, in any one or more of the first to eleventh embodiments, 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.

In a fourteenth embodiment, in any one or more of the first to thirteenth embodiments, 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. .

The above embodiments have been disclosed for the purposes of illustration, and the description is not intended to limit the scope of the invention. Accordingly, various modifications, variations, and substitutions may occur to those skilled in the art without departing from the spirit and scope of the present invention.

Claims (15)

1. A cavity formed in the center; And

   Comprising a hollow porous microspheres including a partition including a micropores surrounding the cavity,

   Compositions for injection of skin tissue regeneration or skin tissue volume enhancement.
2. The composition of claim 1, wherein the hollow porous microspheres have a mean diameter of 5 to 150 μm.
3. The composition of claim 1, wherein the hollow porous microspheres have an average diameter of 50 to 200 μm.
4. The composition of claim 1, wherein the volume of the hollow porous microspheres is 20 to 80% by volume relative to the total volume of the hollow porous microspheres.
5. According to claim 1, wherein the average diameter of the micropores of the hollow porous microspheres is 5 to 50 ㎛ skin tissue regeneration or skin tissue volume injection composition for injection.
6. The composition of claim 1, wherein the porosity of the hollow porous microspheres is on average 20 to 80%.
7. The composition of claim 1 wherein the hollow porous microspheres comprise a hydrophobic biodegradable polymer.
8. The method of claim 7, wherein the hydrophobic biodegradable polymer is poly-L-Lactic Acid (PLLA), polyglycolic acid (PGA), polylactic acid-glycolic acid copolymer (poly (lactic-co-glycolic acid) ), PLGA), poly-ε- (caprolactone) (Polycaprolactone, PCL), polyanhydrides, polyorthoesters, polyviniyalcohol, polyethyleneglycol, polyurethane ( polyurethane, 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, the composition for injection of skin tissue regeneration or skin tissue volume enhancement.
9. The composition of claim 1, wherein the cavity and micropore-forming substance of the hollow porous microspheres are incompatible with hydrophobic biodegradable polymers and are hydrophobic fluids having a lower density than water. .
10. The composition of claim 9, wherein the cavity and micropore-forming substance is at least one selected from the group consisting of alkanes, vegetable oils, and mixtures thereof.
11. The method of claim 10, wherein the alkanes are at least one selected from the group consisting of Octane, Undecane, Tridecane, Tridentane, 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,

    Compositions for injection of skin tissue regeneration or skin tissue volume enhancement.
12. The composition of claim 1, wherein the composition comprises alginic acid, hyaluronic acid, carboxymethyl cellulose, dextran, collagen, gelatin, and elastin (gelatin). elastin) further comprises one or more water-soluble polymers selected from the group consisting of

    Compositions for injection of skin tissue regeneration or skin tissue volume enhancement.
13. The composition of claim 1, wherein the composition comprises 1 to 50% by weight of the hollow porous microspheres relative to the total weight of the composition.
14. The method of claim 1, wherein the skin tissue regeneration or skin tissue volume enhancement is in vivo skin tissue cells migrate through the micropores into the hollow porous microspheres, the migrated skin tissue cells in the central cavity proliferate the skin Skin tissue regeneration or skin tissue volume enhancing injectable composition, which is to regenerate tissue or to enhance volume.
15. The composition for injection of skin tissue regeneration or skin tissue volume enhancement according to any one of claims 1 to 14, wherein the composition is for a skin wrinkle or skin depression site improvement filler.

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