Skin booster composition for improving skin wrinkles and elasticity and method for preparing same

Abstract

The present invention relates to a skin booster composition for improving skin wrinkles and elasticity and a method for preparing same.

Description

Skin booster composition for improving skin wrinkles and elasticity and method for manufacturing the same

[0001] The present invention relates to a skin booster composition for improving skin wrinkles and elasticity, and a method for manufacturing the same.

[0002] As environmental pollution resulting from modern industrialization, as well as fine dust and ultraviolet rays in the atmosphere, have undesirable effects on the skin of modern people, leading to skin roughness and accelerated skin aging, there is a growing demand for preventing dryness and skin roughness by blocking moisture evaporation and maintaining skin moisture for a long time, as well as for improving wrinkles caused by photoaging.

[0003] The skin is the outermost organ of the human body and serves as a barrier protecting our body from harmful external substances such as microorganisms, irritants, and pollutants. The skin is composed of the epidermis, dermis, and subcutaneous fat layer. The epidermis is divided into the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale according to the keratinization process. Most of the cells composing the epidermis are keratinocytes, which form the skin barrier by synthesizing proteins such as transglutaminase-1 and filaggrin, and also participate in skin moisturization by synthesizing hyaluronic acid synthase (HAS), which produces hyaluronic acid, and aquaporin-3, which is involved in the movement of water and glycerol (Jiwon H, et al., 2021). Therefore, strengthening the skin barrier can be considered an essential requirement for skin health.

[0004] Recently, as interest in appearance has risen across all age groups and genders, much research is being conducted to delay and prevent aging, which is the first visible sign on the skin. In particular, with the increasing interest in wrinkles, there is a growing need for cosmetics that address the fact that while innate traits are important for maintaining firm and elastic skin, it can also be improved through dedicated attention and effort.

[0005] The skin, composed of the epidermis, dermis, and subcutaneous fat, is the largest organ of the human body and is a vital organ responsible for various functions, including temperature regulation, excretion, respiration, protection, and barrier function. However, as we age, the skin's functions decline rapidly, leading to various changes and the progression of aging. In particular, reactive oxygen species and free radicals, generated by increased ultraviolet radiation and air pollution, as well as the excessive fatigue and stress experienced by modern people, are known to act as the primary causes of skin aging by oxidizing or denaturing biological components due to their high reactivity; however, the exact cause has not yet been definitively identified.

[0006] Physiological changes in the skin due to aging include thinning of the epidermis, dermis, and subcutaneous tissue, which are components of the skin, and changes in the lipid composition and content of the lipid barrier responsible for skin barrier function, which rapidly deteriorates, resulting in a decrease in skin moisture content, dryness of the skin, and the appearance of melasma, freckles, and pigmentation.

[0007] Recently, various studies have been conducted on changes in the extracellular matrix (ECM) components and collagen, a major component of the ECM, which are particularly closely related to skin wrinkles and elasticity during the aging process. Collagen accounts for 70-80% of the ECM components, and it is known that the rapid decline in its production with age is a cause of wrinkle formation. In addition, research is being conducted on the functional decline resulting from the oxidation of elastin, proteoglycans, glucosaminoglycans, laminin, and fibronectin—which constitute skin connective tissue in addition to collagen—as these are known to be the primary causes of decreased skin elasticity and wrinkle formation.

[0008] The connective tissue fibers of the extracellular matrix (ECM) include collagen fibers, reticular fibers, and elastic fibers. Among these, collagen, which accounts for approximately 70% of skin connective tissue, is mostly formed by skin fibroblasts. As we age, the collagen content within the skin's connective tissue decreases due to a decline in collagen synthesis and the acceleration of its degradation. The process of collagen biosynthesis is regulated by numerous factors involved at both the transcriptional and post-transcriptional levels. Collagen degradation occurs when factors such as ultraviolet radiation stimulate the expression of matrix metalloproteases (MMPs), such as collagenase, which degrade collagen. Along with this decline in synthesis and accelerated degradation, the deformation of collagen due to the external environment is accelerated, leading to more numerous and deeper wrinkles in the skin. Consequently, skin aging phenomena such as sagging, loss of elasticity, and wrinkle formation are caused by cellular heterogeneity, loss of elastin, destruction of collagen, and a decrease or delay in collagen synthesis. Therefore, while skin aging occurs in the epidermis, it can be considered to be a phenomenon that takes place primarily in the dermis. Various cosmetic compositions are being researched to address these issues related to skin aging, and some are showing tangible results regarding wrinkle improvement.

[0009] Originally, wrinkles caused by aging can be defined as grooves forming on the skin surface due to the loss of collagen and elastic fibers in the dermis. While this is a natural phenomenon that occurs with age, the dermis begins to thin after the age of 20, and as the number of fibroblasts decreases, skin thickness diminishes. Furthermore, exposure to environmental factors such as ultraviolet rays causes functional and morphological changes in the basal dermis. In other words, the decrease in the quantity and function of fibroblast products, including collagen and proteoglycans, leads to skin damage and the formation of wrinkles, which can be considered the beginning of skin aging.

[0010] Accordingly, the skin booster exhibits wrinkle improvement effects through ingredients that can delay aging, which is the cause of wrinkle formation, activate the metabolic activity of cells whose function has deteriorated due to aging, expand cellular components or intercellular components, and increase skin resistance.

[0011] However, in the case of skin boosters, the composition within the gel type may separate from the liquid and settle to the bottom, making mixing and dispersion impossible. Consequently, even if the effect is excellent, there is a problem with injecting it into the skin. Additionally, viscosity is also an issue; if the viscosity is high, the active ingredient does not disperse effectively within the gel and continues to clump together, resulting in not only reduced effectiveness but also skin pain and side effects during injection.

[0012] Ultimately, skin aging wrinkles are caused by various factors, and research and development are underway on skin booster compositions for improving skin wrinkles and elasticity that are free from side effects and highly effective for the improvement and prevention of these wrinkles.

[0013] Patent Document 1: Korean Published Patent Document No. 10-2021-0103951

[0014] One embodiment of the present specification aims to provide a skin booster composition for improving skin wrinkles and elasticity and a method for manufacturing the same.

[0015] One embodiment of the present specification provides a skin booster composition for improving skin wrinkles and elasticity, comprising: one or more active substances selected from the group consisting of hydroxyapatite and beta-tricalcium phosphate; hyaluronic acid; and DNA (deoxyribonucleic acid) fragments, wherein, based on 100 parts by weight of the composition, the DNA (deoxyribonucleic acid) fragments are 1 part by weight or less, the active substances are 3 parts by weight or more and 18 parts by weight or less, and the hyaluronic acid is 0.1 parts by weight or more and 3 parts by weight or less.

[0016] One embodiment of the present specification provides a skin booster composition for improving elasticity, wherein the size of the hydroxyapatite is 10 μm or more and 30 μm or less, and the central particle diameter (D50) is 15 μm or more and 20 μm or less.

[0017] According to one embodiment of the present specification, a skin booster composition for improving elasticity is provided in which the hydroxyapatite has a spherical microsphere shape.

[0018] According to one embodiment of the present specification, a skin booster composition for improving elasticity is provided, wherein the hyaluronic acid is cross-linked hyaluronic acid or non-cross-linked hyaluronic acid.

[0019] According to one embodiment of the present specification, a skin booster composition for improving elasticity is provided, wherein the molecular weight of the hyaluronic acid is 1.0 MDa or more and 3.0 MDa or less.

[0020] In one embodiment of the present application, a skin booster composition for improving elasticity is provided, wherein the DNA (Deoxyribonucleic acid) fragment is a polyeoxyribonucleotide (PDRN) or a polynucleotide (PN).

[0021] One embodiment of the present application provides a skin booster composition for improving elasticity, wherein the molecular weight of the polyeoxyribonucleotide (PDRN) is 50 kDa or more and 300 kDa or less, and the molecular weight of the polynucleotide (PN) is 300 kDa or more and 800 kDa or less.

[0022] In the present application, the composition further comprises a solvent and provides a skin booster composition for improving elasticity in an amount of 80 parts by weight or more and 95 parts by weight or less based on 100 parts by weight of the composition.

[0023] One embodiment of the present application provides a skin booster composition for improving elasticity, wherein the composition further comprises one or more selected from the group consisting of peptides, amino acids, vitamins, and collagen.

[0024] The present application provides a method for preparing a skin booster composition for improving elasticity, comprising the steps of: weighing and dissolving DNA (Deoxyribonucleic acid) fragments and a solvent to form a first solution; weighing and dissolving hyaluronic acid in the first solution to form a second solution; weighing and dissolving one or more active substances selected from the group consisting of hydroxyapatite and beta-tricalcium phosphate in the second solution to form a third solution; filling the third solution into a syringe; and steam sterilizing the third solution at a temperature of 100°C to 150°C and for a time of 1 minute to 60 minutes.

[0025] In addition, the present application provides a method for manufacturing a skin booster composition for improving elasticity, wherein the dissolution in each of the above steps is performed using a vacuum mixer or a power mixer, and the mixing conditions are 30 minutes to 200 minutes under conditions of 100 rpm or more and 300 rpm or less.

[0026] Finally, the present application provides a method for manufacturing a skin booster composition for improving elasticity, wherein the temperature of the first solution is 10°C to 30°C, the temperature of the second solution is 5°C to 20°C, and the temperature of the third solution is 15°C to 35°C.

[0027] The skin booster composition according to the present application is characterized by being able to improve skin wrinkles and elasticity, while simultaneously minimizing pain and discomfort upon injection.

[0028] The composition of a skin booster requires proper dispersion of particles and subsequent maintenance to ensure stability during the injection process when injected into the skin. If clumping, phase separation, or settling occurs within the composition, it may be difficult to inject into the skin, cause pain, and, moreover, lead to side effects rather than benefits.

[0029] The skin booster composition according to the present application comprises one or more active substances selected from the group consisting of hydroxyapatite and beta-tricalcium phosphate; hyaluronic acid; and DNA (deoxyribonucleic acid) fragments, and contains a specific amount, thereby having excellent effects in improving skin wrinkles and elasticity.

[0030] Furthermore, it was discovered that the skin booster composition according to the present application can solve the aforementioned problems when each of the compositions contains a specific amount, and thus the present invention was arrived at. That is, when the composition and amount described above are satisfied, the composition does not undergo phase separation with the liquid phase, and the phenomenon of settling to the bottom can be controlled. Additionally, it has an appropriate viscosity, has excellent dispersibility, and can control clumping. Accordingly, stability is ensured during the injection process, and thus the pain during injection is reduced.

[0031] Figure 1 is a figure illustrating a description of hydroxyapatite according to the present application.

[0032] Figure 2 is a figure showing a photograph of the evaluation of the appearance according to the hyaluronic acid content in Group 1 of the present invention.

[0033] Figure 3 is a figure showing a photograph of the evaluation of the appearance according to the hyaluronic acid content in Group 2 of the present invention.

[0034] Figure 4 is a figure showing a photograph of the evaluation of the appearance according to the hyaluronic acid content in Group 3 of the present invention.

[0035] Figure 5 is a figure showing a photograph of the evaluation of the appearance according to the hyaluronic acid content in Group 4 of the present invention.

[0036] Figure 6 is a figure showing a photograph of the evaluation of the appearance according to the hyaluronic acid content in Group 5 of the present invention.

[0037] FIGS. 7 to 11 are figures showing the injection force evaluation results of Comparative Examples 1-1, 2-1, 3-1, 4-1, and 5-1 of the present invention.

[0038] FIGS. 12 to 16 are figures showing the injection force evaluation results of Comparative Example 1-2, Example 2-1, Example 3-1, Example 4-1, and Comparative Example 5-2 of the present invention.

[0039] FIGS. 17 to 21 are figures showing the injection force evaluation results of Comparative Example 1-3, Example 2-2, Example 3-2, Example 4-2 and Comparative Example 5-3 of the present invention.

[0040] FIGS. 22 to 26 are figures showing the injection force evaluation results of Comparative Examples 1-4, Examples 2-3, Examples 3-3, Examples 4-3 and Comparative Example 5-4 of the present invention.

[0041] FIGS. 27 to 31 are figures showing the injection force evaluation results of Comparative Examples 1-5, 2-2, 3-2, 4-2, and 5-5 of the present invention.

[0042] One embodiment of the present specification provides a skin booster composition for improving skin wrinkles and elasticity, comprising: one or more active substances selected from the group consisting of hydroxyapatite and beta-tricalcium phosphate; hyaluronic acid; and DNA (deoxyribonucleic acid) fragments, wherein, based on 100 parts by weight of the composition, the DNA (deoxyribonucleic acid) fragments are 1 part by weight or less, the active substances are 3 parts by weight or more and 18 parts by weight or less, and the hyaluronic acid is 0.1 parts by weight or more and 3 parts by weight or less.

[0043] In order to facilitate understanding of the present invention, examples will be described in detail below. However, the following examples are merely illustrative of the content of the present invention, and the scope of the present invention is not limited to the following examples. The examples of the present invention are provided to more completely explain the present invention to those with average knowledge in the art. The present invention is not limited to the examples presented herein and may be embodied in other forms.

[0044] In the present invention, the separation method for obtaining the compound is not particularly limited and may be carried out according to methods commonly used in the art. A non-limiting example of the separation method is a method of obtaining the compound from a natural substance extract by treating the extract with a predetermined solvent.

[0045] In the present invention, the terms “extracted substance” or “extract” include the extract itself and all formulations of extracts that can be formed using the extract, such as an extract obtained by an extraction process, a diluted or concentrated extract of said extract, a dried product obtained by drying said extract, a modified or purified product of said extract, or a mixture thereof.

[0046] The term "extract" in this specification follows the dictionary definition and may refer to a liquid substance drawn from a specific substance or state.

[0047] The term "extract" in this specification follows the dictionary definition and refers to a product obtained by concentrating a specific component in an extract, wherein a specific active component is separated using a suitable solvent, and the solvent is completely or mostly evaporated to obtain a remaining mass or powder which is then adjusted according to standards. In this specification, the term "extract" may be used to include all three forms: semi-fluid or syrup-like, pill-like or solid, dried powder, etc.

[0048] In the present invention, the drying of the extract can be carried out by known methods to the extent that useful components from the collected natural material are not destroyed, for example, by natural drying in the shade. Additionally, crushing or grinding can be performed to powder the material to the extent that useful components of the plant can be sufficiently extracted during the subsequent extraction process. The drying and crushing or grinding processes may be performed in the reverse order or repeatedly as necessary.

[0049] In the extraction of the present invention, the extraction method is not particularly limited and can be performed according to methods commonly used in the relevant technical field. Non-limiting examples of the extraction method include hot water extraction, ultrasonic extraction, filtration, and reflux extraction, and these may be performed individually or in combination of two or more methods.

[0050] The skin, which serves as the body's primary defense mechanism, protects internal organs from external stimuli while acting as a barrier to prevent moisture from evaporating.

[0051] Skin aging begins with the birth of a living being, and wrinkles and a loss of elasticity are among the symptoms of aging.

[0052] The causes of skin aging are broadly divided into extrinsic and intrinsic factors. Extrinsic factors include sunlight, gravity, and smoking, while intrinsic factors include genetic factors. Furthermore, extrinsic factors include the influence of ultraviolet rays and humidity, while intrinsic factors include genetic mutations and tissue changes.

[0053] Meanwhile, in the domestic anti-aging market, which was previously dominated by botulinum toxin and fillers, items known as skin boosters are recently gaining new attention. Globally, the market is expected to reach $2.1 billion by 2030 and is projected to show an average annual growth rate of 9.6%.

[0054] The aforementioned skin booster refers to a procedure that injects beneficial ingredients into the dermis layer to improve the internal skin environment, resolve skin problems, and promote skin cell regeneration, thereby slowing down aging and restoring skin elasticity.

[0055] Skin boosters currently in use are referred to by various names due to differences in their ingredients and proportions.

[0056] Representative examples include skin boosters that aid in skin regeneration—such as treating fine lines, improving elasticity, and treating scars—by injecting skin-regenerating components derived from salmon DNA fragments into the dermis; skin boosters containing complex ingredients like hyaluronic acid and vitamins that help improve skin tone, hydration, and radiance; and skin boosters containing MGF growth factors that stimulate stem cells and growth factors within the skin to improve the skin.

[0057] Although conventional skin boosters show skin improvement effects, severe pain and discomfort during the procedure are among the typical side effects. Additionally, the rapid biodegradation of the components requires frequent procedures, making them unsuitable as a long-term solution, and the fact that they induce a defensive reaction in the recipient remains a problem that needs to be solved.

[0058] Accordingly, the skin booster composition according to the present application comprises one or more active substances selected from the group consisting of hydroxyapatite and beta tricalcium phosphate; hyaluronic acid; and DNA (deoxyribonucleic acid) fragments, and by including a specific amount, it has excellent effects in improving skin wrinkles and elasticity, and compared to other skin boosters that are rapidly biodegradable, it has a long-term effect due to the active substance (hydroxyapatite or beta tricalcium phosphate).

[0059] Hereinafter, a skin booster composition for improving elasticity according to the present application will be described in detail.

[0060] The skin booster composition according to the present application comprises one or more active substances selected from the group consisting of hydroxyapatite and beta tricalcium phosphate.

[0061] Hydroxyapatite can increase collagen synthesis in fibroblasts and thus can have a well-defined, high specific surface area with particularly high biostimulation.

[0062] The above active substance is particularly effective for fine wrinkles and can be used specifically as a collagen-inducing substance, and calcium ions (Ca 2+ ) It can be selected from a supply agent, ascorbic acid, and combinations thereof, and the active material is a material that is not transparent so as to avoid the problem of the Tyndall effect.

[0063] In the present application, the active material may be hydroxyapatite.

[0064] The above hydroxyapatite may be calcium hydroxyapatite.

[0065] In the present application, the active material may be beta tricalcium phosphate.

[0066] Hydroxyapatite can have any shape. It may be spherical, elliptical, crystalline, random (also irregular), or a mixture of two or more of these. In a preferred embodiment, the hydroxyapatite is spherical or elliptical. In a preferred embodiment, the hydroxyapatite is spherical, and the hydroxyapatite may have a spherical microsphere shape.

[0067] In the present application, hydroxyapatite may have a porous surface. Accordingly, the surface of the hydroxyapatite may preferably not be smooth and may not be tile-shaped, and specifically may have a turtle shell shape.

[0068] Preferably, the surface of the hydroxyapatite has many cavities. Preferably, the interior of the hydroxyapatite may also have many pores / cavities.

[0069] The above pores may have any dimensions. In a preferred embodiment, the surface of the hydroxyapatite has pores with an average diameter of 10 nm to 500 nm when determined by Hg porosimetry. Additionally, the surface may have pores with an average diameter of 20 nm to 300 nm, or 30 nm to 250 nm, or 50 nm to 220 nm.

[0070] In the present application, the size of the hydroxyapatite is 10 μm or more and 30 μm or less, and the central particle size (D50) may be 15 μm or more and 20 μm or less.

[0071] Specifically, the size of the hydroxyapatite may be 10 μm or more and 30 μm or less, 13 μm or more and 28 μm or less, and 15 μm or more and 25 μm or less.

[0072] In addition, the central particle size (D50) of the hydroxyapatite may be 15㎛ or more and 20㎛ or less, 16㎛ or more and 20㎛ or less, or 16㎛ or more and 18㎛ or less.

[0073] When using hydroxyapatite having the size and central particle size as described above, the effect of improving skin wrinkles is excellent, and the stability of the surface during use can also be improved.

[0074] In the present application, beta tricalcium phosphate may also be used as an active material, and as long as it can perform the same role as the hydroxyapatite as a collagen-inducing material, it may be used without limitation on size, particle size, or shape.

[0075] In the present application, the size of the beta tricalcium phosphate may be 10 μm or more and 30 μm or less, 13 μm or more and 28 μm or less, and 15 μm or more and 25 μm or less.

[0076] In the present application, the beta tricalcium phosphate may have various forms, but specifically, it may have a spherical microsphere form.

[0077] In the present application, the beta tricalcium phosphate may have a porous structure, specifically having a porous spherical shape of 20% to 70%.

[0078] In the present application, the active substance may be in an amount of 3 parts by weight or more and 18 parts by weight or less based on 100 parts by weight of the composition.

[0079] In addition, based on 100 parts by weight of the composition, the active substance may be 3 parts by weight or more and 18 parts by weight or less, specifically 4 parts by weight or more and 15 parts by weight or less.

[0080] When the above weight range is satisfied, the injection force is constant and no blockage occurs during skin injection; however, if it is below or above the above range, the injection force is inconsistent and blockage may occur intermittently, and furthermore, the phase becomes unstable, which may lead to a problem of reduced stability.

[0081] The skin booster composition according to the present application may include hyaluronic acid.

[0082] In the present application, the hyaluronic acid may be cross-linked hyaluronic acid or non-cross-linked hyaluronic acid.

[0083] In the present application, the hyaluronic acid may be non-crosslinked hyaluronic acid.

[0084]

[0085] *73 Hyaluronic acid exhibits a wide range of molecular weights depending on the manufacturing and purification methods. It possesses viscosity, elasticity, and moisturizing properties in aqueous solutions, and these properties are closely related to molecular weight and concentration. The method for manufacturing hyaluronic acid according to the present application may utilize acid-base catalysts, high-temperature heating, ultrasound, enzymes, etc.

[0086] It is reported that the amount of hyaluronic acid in human skin decreases with aging, and the liquid composition according to the present application, by including hyaluronic acid, can prevent the decrease in skin elasticity and maintain moisture content, and in particular, has the characteristic of being able to increase the absorption of glutathione into the mucous membrane.

[0087] In other words, hyaluronic acid has a moisturizing effect, and this moisturizing capacity increases as the concentration of hyaluronic acid increases. Furthermore, hyaluronic acid has excellent lubricating properties against physical friction and can aid in the repair of the dermis layer, making it applicable to various fields of the aesthetic and medical industry, such as cosmetic ingredients, facial filler ingredients, and medical extracellular matrix ingredients.

[0088] In the present application, the molecular weight of the hyaluronic acid may be 1.0 MDa or more and 3.0 MDa or less. The MDa may mean megadaltons, and specifically may be 1.0 MDa or more and 2.5 MDa or less.

[0089] In this application, molecular weight refers to the mass of a molecule expressed in atomic mass units. It is also called molecular mass, and since it is a relative mass based on carbon-12, it can also be referred to as relative molecular mass. The molecular weight of a molecule can be calculated as the sum of the atomic masses of the atoms constituting the molecule, and the molecular weight can also be directly measured using a mass spectrometer.

[0090] Hyaluronic acid is a substance that increases water content and provides a lubricating effect against physical friction; in particular, when it has the molecular weight mentioned above, it facilitates the maintenance of viscosity within the composition, resulting in excellent dispersibility and consequently excellent skin injectability.

[0091] In the present application, the active substance may be in an amount of 3 parts by weight or more and 18 parts by weight or less based on 100 parts by weight of the composition.

[0092] In addition, based on 100 parts by weight of the composition, the active substance may be 3 parts by weight or more and 18 parts by weight or less, specifically 4 parts by weight or more and 15 parts by weight or less.

[0093] In the present application, based on 100 parts by weight of the composition, the hyaluronic acid may be 0.1 parts by weight or more and 3 parts by weight or less, specifically 0.2 parts by weight or more and 2.5 parts by weight or less, and more specifically 0.3 parts by weight or more and 3 parts by weight or less.

[0094] When the above weight range is satisfied, the injection force is constant during skin injection, clogging does not occur, and the two compositions do not separate after mixing, allowing for stable dispersion; furthermore, the viscosity is appropriate, which controls clumping. That is, if the range is below or above, the injection force is inconsistent and clogging may occur intermittently; additionally, the phase may become unstable, leading to reduced stability; and due to high viscosity, it does not disperse and may cause problems when applied to the skin due to layering and clumping.

[0095] In the present application, the skin booster composition may include DNA (Deoxyribonucleic acid) fragments, and the DNA (Deoxyribonucleic acid) fragments may be polydeoxyribonucleotide (PDRN) or polynucleotide (PN).

[0096] The above PN and PDRN are similar in that they contain DNA fragments, but they differ in their major chemical structures: PN is a mixture containing both RNA and DNA fragments, whereas PDRN consists only of DNA fragments and can be 50-2000 bp in length; and regarding the source of extraction, PN is mainly extracted from salmon sperm, whereas PDRN can be extracted and purified from trout or salmon sperm DNA.

[0097] The present application provides a skin booster composition for improving elasticity, wherein the molecular weight of the polyeoxyribonucleotide (PDRN) is 50 kDa or more and 300 kDa or less, and the molecular weight of the polynucleotide (PN) is 300 kDa or more and 800 kDa or less.

[0098] In addition, in the present application, the molecular weight of the polynucleotide (PN) may be 300 kDa or more and 800 kDa or less, specifically 310 kDa or more and 750 kDa or less.

[0099] In addition, in the present application, the molecular weight of the polyeoxyribonucleotide (PDRN) may be 50 kDa or more and 300 kDa or less, specifically 60 kDa or more and 250 kDa or less.

[0100] In the present application, the DNA (Deoxyribonucleic acid) fragment may be 1 part by weight or less based on 100 parts by weight of the composition, specifically 0.95 parts by weight or less, and 0.3 parts by weight or more, specifically 0.5 parts by weight or more.

[0101] In the present invention, the composition further comprises a solvent, and may be 80 parts by weight or more and 95 parts by weight or less based on 100 parts by weight of the composition.

[0102] Specifically, any solvent capable of dissolving the composition of the aforementioned skin booster composition may be used without limitation; specifically, physiological saline may be used, and more specifically, phosphate-buffered saline (PBS) may be used.

[0103] In addition, the above skin booster composition may further include additional additives to improve skin wrinkles and elasticity, and specifically, the composition may further include one or more selected from the group consisting of peptides, amino acids, vitamins, and collagen.

[0104] In addition, when formulating the above skin booster, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

[0105] The skin booster composition of the present invention can be prepared in any formulation conventionally manufactured in the industry, for example, as a solution, suspension, emulsion, paste, gel, cream, lotion, powder, surfactant-containing cleansing, powder foundation, emulsion foundation, wax foundation, and spray, but is not limited thereto. More specifically, it can be prepared in the form of a softening lotion, a nourishing lotion, a nourishing cream, a massage cream, an essence, an eye cream, or a wash-off pack.

[0106] In the case where the formulation of the present invention is a paste, cream, or gel, animal oil, vegetable oil, wax, paraffin, starch, cellulose derivative, polyethylene glycol, silicone, bentonite, kaolin, silica, talc, or zinc oxide may be used as a carrier component.

[0107] When the formulation of the present invention is a solution or an emulsion, a solvent, a solubilizing agent, or an emulsifying agent is used as a carrier component, such as water, ethanol, glycerin, methylpropanol, pentylene glycol, isoprene glycol, propylene glycol, 1,3-butylene glycol, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan. When the formulation of the present invention is a suspension, a liquid diluent such as water, ethanol, or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, or tracanthera may be used as a carrier component. In the case where the formulation of the present invention is a cleansing agent containing a surfactant, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, fatty acid amide ether sulfate, alkylamidobetaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, or ethoxylated glycerol fatty acid ester, etc. may be used as a carrier component.

[0108] The present application provides a method for preparing a skin booster composition for improving elasticity, comprising the steps of: weighing and dissolving DNA (Deoxyribonucleic acid) fragments and a solvent to form a first solution; weighing and dissolving hyaluronic acid in the first solution to form a second solution; weighing and dissolving one or more active substances selected from the group consisting of hydroxyapatite and beta-tricalcium phosphate in the second solution to form a third solution; filling the third solution into a syringe; and steam sterilizing the third solution at a temperature of 100°C to 150°C and for a time of 1 minute to 60 minutes.

[0109] Dissolution at each stage can be performed using a vacuum mixer (small amount) or a power mixer (large amount), and specifically, dissolution can be performed for 30 minutes to 200 minutes under conditions of 100 rpm or more and 300 rpm or less.

[0110] In addition, the process of preparing the first solution, the second solution, and the third solution may further include a filtration step, specifically, the mixed solution may be filtered with a 0.2 μm filter.

[0111] In addition, the temperature of the first solution may be 10°C to 30°C, the temperature of the second solution may be 5°C to 20°C, and the temperature of the third solution may be 15°C to 35°C.

[0112] By maintaining the temperature range as described above, it has the characteristic of being able to improve clumping and dispersibility within the composition.

[0113] The present invention will be explained in more detail below through examples. These examples are intended to explain the invention more specifically, and the scope of the invention is not limited by these examples according to the gist of the invention.

[0114] <Preparation Example>

[0115] <Specifications of Key Ingredients>

[0116] The present invention relates to a skin booster composition for improving skin wrinkles and elasticity, and a method for manufacturing the same.

[0117] As shown in Table 1 below, the above composition includes a nucleic acid of calcium hydroxyapatite, hyaluronic acid, PN (polynucleotide), or PDRN (polydeoxyribonucleotide) as a major component.

[0118] [Hydroxyapatite Skin Booster]

[0119] Approval: Class 2 Medical Device (Wound Dressing) / Cosmetics

[0120] Main Ingredients Ingredient Specs Calcium Hydroxyapatite Size: 15–25 microns Form: Spherical microspheres Surface Shape: Turtle shell-like Hyaluronic Acid Molecular Weight: 1.0 MDa–2.5 MDa Uncrosslinked or crosslinked HAPN or PDRN PDRN: 80–200 kDa PN: 500–700 kDa Others: Peptides, amino acids, vitamins, collagen

[0121] <Preparation of Skin Booster Composition> A first solution was prepared by weighing and dissolving PBS (Phosphate Buffered Saline) and PDRN (molecular weight 80~300 KDa), and then a second solution was prepared by weighing and adding Hyaluronic Acid (molecular weight 1.0 MDa~2.0 MDa) to the first solution after dissolution was complete and dissolving it.

[0122] Subsequently, Calcium Hydroxyapatite (size 15–25 micro) was weighed and added to the second solution after dissolution was complete, and the mixture was mixed. The prepared solution was then filled into glass vials and syringes. Afterward, it was autoclaved at 121°C for 30 minutes. To ensure the dispersion stability of CaHA, a pH buffer salt-based interfacial stabilization was applied without surfactants. In addition, a simultaneous dispersion process of high molecular weight HA (hyaluronic acid) + PN + CaHA (calcium hydroxyapatite) was applied, and temperature and stirring speed conditions were controlled to prevent particle aggregation and maintain biocompatibility.

[0123] At this time, a skin booster composition was prepared with the composition having the specifications of Table 1 above and the weighing conditions of Table 2.

[0124] Group Sample PDRNPBS Calcium Hydroxyapatite Hyaluronic Acid 1 Comparative Example 1-10.997.120 Comparative Example 1-20.996.60.5 Comparative Example 1-30.995.61.5 Comparative Example 1-40.994.13 Comparative Example 1-50.993.142 Comparative Example 2-10.995.140 Example 2-10.994.60.5 Example 2-20.993.61.5 Example 2-30.992.13 Comparative Example 2-20.991.143 Comparative Example 3-10.991.180 Example 3-10.990.60.5 Example 3-20.989.61.5 Example 3-30.988.13 Comparative Example 3-20.987.144 Comparative Example 4-10.984.1150 Example 4-10.983.60.5 Example 4-20.982.61.5 Example 4-30.981.13 Comparative Example 4-20.980.145 Comparative Example 5-10.979.1200 Comparative Example 5-20.978.60.5 Comparative Example 5-30.977.61.5 Comparative Example 5-40.976.13 Comparative Example 5-50.975.14

[0125] Specifically, in Table 2 above, each group prepared a composition by fixing the content of calcium hydroxyapatite and varying the content of hyaluronic acid. Experimental Example 1 Evaluation of properties according to the content of calcium hydroxyapatite and hyaluronic acid

[0126] Using the composition of Table 2, the properties of Calcium Hydroxyapatite and Hyaluronic Acid according to their content were observed and evaluated.

[0127] As a result, as shown in FIGS. 2 to 6, in the case of Comparative Examples 1-1, 2-1, 3-1, 4-1, and 5-1, which contain 0% by weight of no Hyaluronic Acid and 2-20% by weight of Calcium Hydroxyapatite, mixing and dispersion were impossible due to the phenomenon of phase separation immediately after mixing and settling to the bottom. However, under the condition of 0.5-3% by weight of Hyaluronic Acid and 4-15% by weight of Calcium Hydroxyapatite (Example of the present invention), it was confirmed that the substance was well dispersed without phase separation or settling.

[0128] On the other hand, for all conditions containing 2 to 20 wt% of Calcium Hydroxyapatite with 4 wt% of Hyaluronic Acid (Comparative Examples 1-5, 2-2, 3-2, 4-2, and 5-5), the gel actually clumped together and granulated, confirming that it did not exhibit suitable physical properties and characteristics as an injector. Proper dispersion and maintenance of Calcium Hydroxyapatite particles have a stable effect during the injection process as a skin injection composition.

[0129] Experimental Example 2 Evaluation of Injection Power According to Calcium Hydroxyapatite and Hyaluronic Acid Contents

[0130] Using the composition of Table 2, the injection power according to the content of Calcium Hydroxyapatite and Hyaluronic Acid was measured and evaluated, and the results are shown in Table 3 below.

[0131] The injection force was evaluated under the following conditions.

[0132] - Needle Gauge: 30G

[0133] - Measurement speed: 12 mm / min

[0134] - Measurement range: 20mm

[0135] Table 3 corresponds to the review of the results of analyzing the results of Figures 7 to 31 according to the present application.

[0136] It can be seen that in the case where 0% by weight of Hyaluronic Acid is not contained and Calcium Hydroxyapatite is 2 to 20% by weight (Comparative Example 1-1, Comparative Example 2-1, Comparative Example 3-1, Comparative Example 4-1, and Comparative Example 5-1), although injected with a low N force, clogging occurred intermittently during measurement due to rapid phase separation, making measurement impossible.

[0137] In addition, it was found that under conditions where Hyaluronic Acid was 0.5 to 3 wt% and Calcium Hydroxyapatite was 2 wt% (Comparative Examples 1-2 to 1-4) and 20% (Comparative Examples 5-2 to 5-4), the N value was unstable, making measurement impossible due to spikes or blockages in the Pig value.

[0138] In addition, all conditions with 4% by weight of Hyaluronic Acid and 2-20% by weight of Calcium Hydroxyapatite (Comparative Examples 5-1 to 5-5) could not be measured because the high viscosity was outside the measurement range.

[0139] On the other hand, under conditions where Hyaluronic Acid is 0.5~3 wt% and Calcium Hydroxyapatite is 4~15 wt%, it was confirmed that a stable and constant N value of 30 N or less was measured, and accordingly, it was found that there was no problem with the injection power.

[0140] Review of Results Comparative Example 1-1: The lowest N value drops below 1N, showing irregularity due to phase-separated Calcium Hydroxy apatite Comparative Example 1-2: Main input is inconsistent, with intermittent blockage Comparative Example 1-3: Intermittent blockage Comparative Example 1-4: Main input is inconsistent, with intermittent blockage Comparative Example 1-5: Significantly unstable and blockage occurs Comparative Example 2-1: Irregular due to phase-separated Calcium Hydroxy apatite, making measurement impossible due to intermittent blockage Example 2-1: Consistent and stable Example 2-2: Consistent and stable Example 2-3: Consistent and stable Comparative Example 2-2: Significantly unstable and blockage occurs Comparative Example 3-1: Irregular due to phase-separated Calcium Hydroxy apatite, making measurement impossible due to intermittent blockage Example 3-1: Consistent and Stability Example 3-2 Constant and stable Example 3-3 Constant and stable Comparative Example 3-2 Significantly unstable and clogging occurs Comparative Example 4-1 Clogging and inability to measure due to phase-separated Calcium Hydroxy apatite Example 4-1 Constant and stable Example 4-2 Constant and stable Example 4-3 Constant and stable Comparative Example 4-2 Significantly unstable and clogging occurs Comparative Example 5-1 Clogging and inability to measure due to phase-separated Calcium Hydroxy apatite Comparative Example 5-2 Unstable and clogging occurs Comparative Example 5-3 Unstable and clogging occurs Comparative Example 5-4 Unstable and clogging occurs Comparative Example 5-5 Out of measurement range and inability to measure

[0141] Experimental Example 3 Evaluation of viscoelasticity according to the content of Calcium Hydroxyapatite and Hyaluronic Acid. Using the composition of Table 2, the viscoelasticity according to the content of Calcium Hydroxyapatite and Hyaluronic Acid was measured and evaluated, and the results are shown in Table 4 below.

[0142] The viscoelasticity measurement conditions were as follows.

[0143] - Equipment: Rotating Rheometer (TA Instruments DHR-2, Kinexus Rheometer)

[0144] - Measurement Geometry: 40mm leveling plate

[0145] - Amplitude sweep: 1Hz, strain 0.01~100%

[0146] - Frequency sweep: 0.1–10 Hz, measured within the LVER (linear viscoelastic region)

[0147] - Adhesion: Normal force measurement when changing plate spacing from 1 to 20 mm

[0148] - Temperature: 25℃

[0149] G'(1Hz, Pa)G" (1Hz, Pa)tan δ Comparative Example 1-1200.00 Comparative Example 1-2500.00 Comparative Example 1-32510.04 Comparative Example 1-46510.02 Comparative Example 1-5UnmeasurableUnmeasurableUnmeasurable Comparative Example 2-1400.00 Example 2-1119170.14 Example 2-2149230.15 Example 2-3219280.13 Comparative Example 2-2UnmeasurableUnmeasurableUnmeasurable Comparative Example 3-1500.00 Example 3-1123180.15 Example 3-2156240.15 Example 3-3218350.16 Comparative Example 3-2UnmeasurableUnmeasurableUnmeasurable 4-1600.00 Example 4-1153200.13 Example 4-2165250.15 Example 4-3235380.16 Comparative Example 4-2 Unmeasurable Unmeasurable Unmeasurable Comparative Example 5-1600.00 Comparative Example 5-2 Unmeasurable Unmeasurable Unmeasurable Comparative Example 5-3 Unmeasurable Unmeasurable Unmeasurable Comparative Example 5-4 Unmeasurable Unmeasurable Unmeasurable Comparative Example 5-5 Unmeasurable Unmeasurable Unmeasurable

[0150] As shown in Table 4, in the case where Hyaluronic Acid was not contained at 0 wt% and Calcium Hydroxyapatite was 2 to 20 wt% (Comparative Examples 1-1, 2-1, 3-1, 4-1, and 5-1), measurement was impossible due to low viscosity, and in the case of Comparative Examples 1-1 to 1-5, the G" value could not be calculated, meaning that meaningless values ​​were measured as an elastic gel. In addition, in the case of Comparative Examples 1-5, 2-2, 3-2, 4-2, and 5-5, where the hyaluronic acid content was 4 wt%, and Comparative Examples 5-1 to 5-5, where the calcium hydroxyapatite was 20 wt%, measurement was impossible because the high viscosity exceeded the measurement range. In other words, it was found that dispersion was not well achieved due to the high viscosity.

[0151] On the other hand, in the condition where Hyaluronic Acid is 0.5 to 3 wt% and Calcium Hydroxyapatite is 4 to 15 wt% (Example), the G' value, which measures the firmness of the gel, was measured as a significant value of 100 Pa to 250 Pa, and when observing the tan δ, which represents the balance between G' and G" viscosity and elasticity, which tended to consistently maintain a value of 0.1 to 0.2, it was found that all compositions under the corresponding conditions maintained a constant ratio of viscosity and elasticity.

[0152] As a result, it was found through the above experiment that the skin booster composition according to the present application satisfies the aforementioned composition and content, so that the composition does not undergo phase separation with the liquid phase, the phenomenon of settling to the bottom can be controlled, and it also has an appropriate viscosity, excellent dispersibility, and can control clumping, and accordingly, stability is ensured during the injection process, and pain is reduced during injection.

Claims

1. A skin booster composition for improving skin wrinkles and elasticity comprising one or more active substances selected from the group consisting of hydroxyapatite and beta-tricalcium phosphate; hyaluronic acid; and DNA (deoxyribonucleic acid) fragments, Based on 100 parts by weight of the above composition, the DNA (Deoxyribonucleic acid) fragment is 1 part by weight or less, and Based on 100 parts by weight of the above composition, the above active substance is 3 parts by weight or more and 18 parts by weight or less, and A skin booster composition for improving elasticity, wherein the hyaluronic acid is 0.1 parts by weight or more and 3 parts by weight or less based on 100 parts by weight of the above composition.

2. In Claim 1, A skin booster composition for improving elasticity, wherein the size of the hydroxyapatite is 10 μm or more and 30 μm or less, and the central particle diameter (D50) is 15 μm or more and 20 μm or less.

3. In Claim 1, A skin booster composition in which the above-mentioned hydroxyapatite has a spherical microsphere shape.

4. A skin booster composition according to claim 1, wherein the hyaluronic acid is cross-linked hyaluronic acid or non-cross-linked hyaluronic acid.

5. A skin booster composition according to claim 1, wherein the molecular weight of the hyaluronic acid is 1.0 MDa or more and 3.0 MDa or less.

6. In Claim 1, A skin booster composition in which the above DNA (Deoxyribonucleic acid) fragment is a polydeoxyribonucleotide (PDRN) or a polynucleotide (PN).

7. In Claim 6, The molecular weight of the above polyeoxyribonucleotide (PDRN) is 50 kDa or more and 300 kDa or less, and A skin booster composition in which the molecular weight of the above polynucleotide (PN) is 300 kDa or more and 800 kDa or less.

8. In Claim 1, The above composition further includes a solvent, and A skin booster composition having 80 parts by weight or more and 95 parts by weight or less based on 100 parts by weight of the above composition.

9. In Claim 1, A skin booster composition comprising one or more selected from the group consisting of peptides, amino acids, vitamins, and collagen.

10. A step of weighing and dissolving DNA (Deoxyribonucleic acid) fragments and a solvent to form a first solution; A step of forming a second solution by weighing and dissolving hyaluronic acid in the first solution; A step of forming a third solution by weighing and dissolving an active substance composed of hydroxyapatite in the second solution; The step of filling the above third solution into a syringe; and A method for preparing a skin booster composition comprising the step of steam sterilizing the above third solution at a temperature of 100°C to 150°C and a time of 1 minute to 60 minutes, A method for manufacturing a skin booster composition in which the size of the above-mentioned hydroxyapatite is 10㎛ or more and 30㎛ or less, and the central particle diameter (D50) is 15㎛ or more and 20㎛ or less.

11. In Claim 10, Dissolution at each of the above steps is performed using a vacuum mixer or a power mixer, and A method for manufacturing a skin booster composition, wherein the mixing conditions are 100 rpm or more and 300 rpm or less for 30 minutes to 200 minutes.

12. In Claim 10, The temperature of the first solution is 10℃ to 30℃, and The temperature of the second solution is 5℃ to 20℃, and A method for preparing a skin booster composition in which the temperature of the third solution is 15℃ to 35℃.

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