KR102917179B1 - A Composition for improving acne comprising colloidal sulfur complex and a manufacturing method thereof - Google Patents

Abstract

The present invention relates to an acne-improving composition comprising a colloidal sulfur complex as an active ingredient and a method for preparing the same. When the composition comprising sulfur, hesperidin, and succinic acid as active ingredients of the present invention is used, excessive sebum production can be suppressed and excessive sebum production can be controlled. In addition, the composition comprising sulfur, hesperidin, and succinic acid as active ingredients of the present invention has an excellent antibacterial effect against C. acnes, an acne-causing bacteria, and thus can be usefully used as an acne-improving functional cosmetic and an acne treatment product containing the same.

Description

{A composition for improving acne comprising colloidal sulfur complex and a manufacturing method thereof}

The present invention relates to an acne improvement composition comprising a colloidal sulfur complex as an active ingredient and a method for preparing the same. Specifically, the present invention relates to an acne improvement composition comprising sulfur, hesperidin, and succinic acid as active ingredients and a method for preparing the same.

Sebocytes are cells that make up the sebaceous glands and secrete sebum through a holocrine process. Sebum is mainly composed of cell debris and neutral lipids such as triglycerides, wax, esters, squalene, cholesterol, and free fatty acids. Sebum is secreted from sebaceous sacs made of sebocytes. When sebum is secreted excessively, a bottleneck occurs, forming a comedone. When sebum is filled and oxidized, a blackhead is formed. Excessive sebum produced by external stimuli such as UV rays and heat becomes food for acne bacteria, and the proliferation of acne bacteria can cause skin problems such as inflammatory acne (or pustular acne).

Androgen, a male hormone known as an inducer of sebum hypersecretion, is one of the direct factors that increases sebaceous gland proliferation. Androgen binds to the androgen receptor (AR), triggering a network process. Androgen-mediated signaling is known to contribute to maximizing sebocyte differentiation and sebaceous lipogenesis. Clinical studies have demonstrated that modulating androgen-mediated signaling plays a crucial role not only in controlling sebum hypersecretion in female acne patients but also in the treatment of acne.

Acetyl-coenzyme A carboxylase (ACC) is a crucial factor in regulating lipid metabolism. Ultimately, since fatty acids comprise the largest component of sebum, ACC acts as a key regulator of sebum production. ACC is regulated by sterol regulatory element-binding protein (SREBP). One study reported that androgen treatment of female hamsters activated SREBP-1, increased sebum cell size, and increased lipid synthesis. Furthermore, the expression of genes involved in fatty acid synthesis, such as ACC, was significantly increased.

Fatty acid synthase (FAS) is an enzyme essential for fatty acid synthesis and is induced by androgens to promote the lipid synthesis pathway. Among the components of sebum, triglycerides (1 glycerol + 3 fatty acids) account for approximately 50%, while fatty acids not included in triglycerides account for approximately 30%, making up the majority of sebum. Fatty acids are overproduced by bacterial breakdown of triglycerides, leading to inflammatory acne.

ACC, a key factor regulating lipid metabolism, catalyzes the formation of FAS through fatty acid chain elongation and increases fatty acid oxidation. When sebum, which contains fatty acids, is oxidized, it triggers the initial formation of acne and the formation of comedones, which are then induced by bacteria to cause inflammatory acne. Because the primary cause of acne is sebum overproduction and imbalance, regulating lipid production is a crucial treatment option for acne patients. Specifically, inhibiting gene expression in pathways related to sebum biosynthesis, such as ACC or FAS, can be effective in regulating sebum production.

Studies have shown that the expression of the pro-inflammatory cytokine IL-1α is highly increased as acne develops. In particular, representative components of the gram-positive bacteria (e.g., Cutibacterium acnes ), such as pathogen-associated molecular patterns (PAMs) and lipopolysaccharide (LPS), activate toll-like receptors (TLRs) TLR-2, TLR-4, and TLR-9, and secrete cytokines such as IL-1α through an NF-κB-dependent mechanism. Among these, TLR-2 in particular acts as a receptor for the gram-positive bacteria C. acnes and acts as a factor contributing to the formation of inflammatory acne. When TLR-2 is activated by C. acnes , various inflammatory genes are expressed and induce the infiltration of immune cells, which plays a critical role in the development of inflammatory acne.

The present inventors studied a material having acne improvement efficacy, sebum secretion control efficacy, and pore tightening efficacy, and confirmed that a stabilized colloidal sulfur complex suppresses excessive sebum production and regulates excessive sebum production. In addition, the inventors confirmed that the colloidal sulfur complex inhibits the expression of TLR-2, which contributes to inflammatory acne, and inhibits the growth of C. acnes , an acne-causing bacteria, thereby elucidating that the stabilized colloidal sulfur complex can be used as a cosmetic composition for acne improvement, thereby completing the present invention.

Republic of Korea Patent Publication No. 10-2021-0034797 (published on March 31, 2021)

The inventors of the present invention have diligently researched and developed a material with acne-improving and sebum-regulating properties. As a result, they discovered that a composition containing sulfur, hesperidin, and succinic acid can effectively improve, prevent, or treat acne by controlling excessive sebum production and inhibiting the growth of the acne-causing bacteria , C. acnes. This discovery led to the completion of the present invention.

Accordingly, the purpose of the present invention is to provide a cosmetic composition for controlling sebum secretion or improving acne, which contains sulfur, hesperidin, and succinic acid as active ingredients.

Another object of the present invention is to provide a pharmaceutical composition for preventing or treating acne, comprising sulfur, hesperidin, and succinic acid as active ingredients.

Another object of the present invention is to provide an antibacterial composition against Cutibacterium acnes comprising sulfur, hesperidin, and succinic acid as active ingredients.

Another object of the present invention is to provide a method for preparing a composition comprising sulfur, hesperidin, and succinic acid.

To address the above-described problems, the inventors of the present invention have conducted extensive research to develop a material with acne-improving and sebum-regulating effects. As a result, they have discovered that a composition comprising sulfur, hesperidin, and succinic acid can effectively improve, prevent, or treat acne by controlling excessive sebum production and inhibiting the growth of the acne-causing bacteria , C. acnes , thereby completing the present invention.

According to one aspect of the present invention, the present invention provides a cosmetic composition for controlling sebum secretion or improving acne, comprising sulfur, hesperidin, and succinic acid as active ingredients.

In the present invention, "sulfur" is a finely ground, pale yellow powder with pain-relieving, anti-inflammatory, detoxifying, and sterilizing effects. Sulfur is heat-toxic and must be processed before use. Depending on the processing method, it is classified into water-soluble and fat-soluble sulfur.

In one embodiment of the present invention, the sulfur of the present invention is dispersed in a colloidal state within the composition. Compared to existing sulfur, the particles are smaller and have better solubility in water.

The sulfur of the present invention may exist in a non-solvated form as well as a colloidal form. Furthermore, the sulfur of the present invention may exist in a crystalline or amorphous form, and all such physical forms are included within the scope of the present invention.

In the present invention, "hesperidin" is a compound represented by the following chemical formula 1 and is a flavanone glycoside among flavonoid pigments. It is a light yellow crystal or crystalline powder and has anti-aging and antioxidant properties:

[Chemical Formula 1]

.

In the present invention, “succinic acid” is a compound represented by the following chemical formula 2, which is a colorless, odorless, columnar or plate-shaped crystalline solid:

[Chemical Formula 2]

.

The sulfur, hesperidin, and succinic acid used in the present invention are not particularly limited in their acquisition method, and may be chemically synthesized by a method known in the art, or commercially available materials may be used.

In the present invention, the term “comprising as an active ingredient” means including an amount sufficient to achieve the efficacy or activity of the sulfur, hesperidin, and succinic acid.

The term "acne" in the present invention refers to an inflammatory skin disease of the sebaceous glands that presents with various skin lesions such as closed or open comedones, papules, pustules, cysts, and nodules on the face, upper chest, back, and upper limbs. The main causes of acne include excessive sebum secretion, abnormal follicular keratinization, proliferation and inflammation of Cutibacterium acnes , and other hormonal or immunological factors may be involved. The above factors act in a complex manner to cause acne lesions.

In the present invention, the term "improvement" means any action that at least reduces the degree of acne symptoms by administering a composition comprising sulfur, hesperidin, and succinic acid as active ingredients according to the present invention.

In the present invention, the term "sebum secretion control" means any action that at least reduces excessive sebum or the degree of sebum production by administering a composition comprising sulfur, hesperidin, and succinic acid as active ingredients according to the present invention.

In the present invention, the term "colloidal sulfur complex" means a mixture in which sulfur, hesperidin, and succinic acid are contained in the following ratios and solubilized through dispersion.

In one embodiment of the present invention, the sulfur may be included in a proportion of 0.001 wt% to 30 wt% based on the total weight of the composition. More specifically, 0.001 wt% to 30 wt%, 0.001 wt% to 25 wt%, 0.001 wt% to 20 wt%, 0.001 wt% to 15 wt%, 0.001 wt% to 10 wt%, 0.001 wt% to 7 wt%, 0.001 wt% to 5 wt%, 0.01 wt% to 30 wt%, 0.01 wt% to 25 wt%, 0.01 wt% to 20 wt%, 0.01 wt% to 15 wt%, 0.01 wt% to 10 wt%, 0.01 wt% to 7 wt%, 0.01 wt% to 5 wt%, 0.1 wt% to 30 wt%, 0.1 wt% to 25 wt%, 0.1 wt% to 20 It may be included in a ratio of, but is not limited to, 0.1 wt% to 15 wt%, 0.1 wt% to 10 wt%, 0.1 wt% to 10 wt%, 0.1 wt% to 7 wt%, 0.1 wt% to 5 wt%, 1 wt% to 30 wt%, 1 wt% to 25 wt%, 1 wt% to 20 wt%, 1 wt% to 15 wt%, 1 wt% to 10 wt%, 1 wt% to 7 wt%, 1 wt% to 5 wt%. If it contains less than 0.001 wt%, the efficacy of sulfur is insufficient, and if it exceeds 30 wt%, there may be concerns about skin irritation and problems of stability and efficacy reduction due to difficulty in dissolving and separation.

In one embodiment of the present invention, the hesperidin may be included in a proportion of 0.001 wt% to 30 wt% based on the total weight of sulfur. More specifically, 0.001 wt% to 30 wt%, 0.001 wt% to 25 wt%, 0.001 wt% to 20 wt%, 0.001 wt% to 15 wt%, 0.001 wt% to 10 wt%, 0.001 wt% to 7 wt%, 0.001 wt% to 5 wt%, 0.01 wt% to 30 wt%, 0.01 wt% to 25 wt%, 0.01 wt% to 20 wt%, 0.01 wt% to 15 wt%, 0.01 wt% to 10 wt%, 0.01 wt% to 7 wt%, 0.01 wt% to 5 wt%, 0.1 wt% to 30 wt%, 0.1 wt% to 25 wt%, 0.1 wt% to Hesperidin may be included in a ratio of 20 wt%, 0.1 wt% to 15 wt%, 0.1 wt% to 10 wt%, 0.1 wt% to 10 wt%, 0.1 wt% to 7 wt%, 0.1 wt% to 5 wt%, 1 wt% to 30 wt%, 1 wt% to 25 wt%, 1 wt% to 20 wt%, 1 wt% to 15 wt%, 1 wt% to 10 wt%, 1 wt% to 7 wt%, 1 wt% to 5 wt%, but is not limited thereto. When hesperidin is included in an amount of less than 0.001 wt% based on the total weight of sulfur, it is not easy to obtain the expected acne-prone skin improvement effect, and when it is included in an amount exceeding 30 wt%, it is difficult to expect an additional increase in acne-prone skin improvement effect.

In one embodiment of the present invention, the succinic acid may be included in a proportion of 0.001 wt% to 30 wt% based on the total weight of sulfur. More specifically, 0.001 wt% to 30 wt%, 0.001 wt% to 25 wt%, 0.001 wt% to 20 wt%, 0.001 wt% to 15 wt%, 0.001 wt% to 10 wt%, 0.001 wt% to 7 wt%, 0.001 wt% to 5 wt%, 0.01 wt% to 30 wt%, 0.01 wt% to 25 wt%, 0.01 wt% to 20 wt%, 0.01 wt% to 15 wt%, 0.01 wt% to 10 wt%, 0.01 wt% to 7 wt%, 0.01 wt% to 5 wt%, 0.1 wt% to 30 wt%, 0.1 wt% to 25 wt%, 0.1 wt% to It may be included in a ratio of 20 wt%, 0.1 wt% to 15 wt%, 0.1 wt% to 10 wt%, 0.1 wt% to 10 wt%, 0.1 wt% to 7 wt%, 0.1 wt% to 5 wt%, 1 wt% to 30 wt%, 1 wt% to 25 wt%, 1 wt% to 20 wt%, 1 wt% to 15 wt%, 1 wt% to 10 wt%, 1 wt% to 7 wt%, 1 wt% to 5 wt%, but is not limited thereto. When succinic acid is included in an amount of less than 0.001 wt% based on the total weight of sulfur, it is not easy to obtain the expected acne-prone skin improvement effect, and when it is included in an amount exceeding 30 wt%, it is difficult to expect an additional increase in acne-prone skin improvement effect.

In the present invention, the composition comprising the sulfur, hesperidin, and succinic acid may reduce the expression levels of ACC (acetyl-coenzyme A carboxylase), FAS (fatty acid synthase), and AR (androgen receptor).

In the present invention, the term "acetyl-coenzyme A carboxylase (ACC)" is one of the rate-limiting enzymes of fatty acid synthesis, which synthesizes malonyl-coenzyme A by attaching a carboxyl group to acetyl-coenzyme A, and malonyl-coenzyme A combines with another acetyl-coenzyme A to produce a long-chain fatty acid.

In one embodiment of the present invention, when a group of sebum cells treated with DHT (dihydrotestosterone) was treated with a composition containing sulfur, hesperidin, and succinic acid, it was confirmed that the amount of ACC expression was significantly reduced compared to a group that was not treated with the composition containing sulfur, hesperidin, and succinic acid.

In the present invention, the term "fatty acid synthase (FAS)" is an enzyme responsible for fatty acid synthesis, which synthesizes palmitic acid from acetyl coenzyme A and malonyl coenzyme A using NADPH.

In one embodiment of the present invention, when a composition containing sulfur, hesperidin, and succinic acid was treated on a group of sebum cells treated with DHT, it was confirmed that the amount of FAS expression was significantly reduced compared to a group that was not treated with the composition containing sulfur, hesperidin, and succinic acid.

In the present invention, the term "androgen receptor (AR)" refers to a receptor of the male hormone androgen, which is a direct factor that increases sebaceous gland proliferation, androgen increases sebum cell differentiation and sebum secretion lipid production by binding to the androgen receptor.

In one embodiment of the present invention, when a composition containing sulfur, hesperidin, and succinic acid was treated on a group of sebum cells treated with DHT, it was confirmed that the amount of AR expression was significantly reduced compared to a group that was not treated with the composition containing sulfur, hesperidin, and succinic acid.

Therefore, it was confirmed that a composition containing sulfur, hesperidin, and succinic acid has an inhibitory activity against excessive sebum production or an inhibitory activity against sebum production.

In the present invention, the composition comprising the sulfur, hesperidin, and succinic acid may reduce the expression level of TLR-2.

In the present invention, the term "toll-like receptor-2 (TLR-2)" acts as a receptor for Cutibacterium acnes and acts as a factor contributing to the formation of inflammatory acne.

In one embodiment of the present invention, when a composition containing sulfur, hesperidin, and succinic acid was treated on a group of sebum cells treated with LPS, it was confirmed that the expression level of TLR-2 was significantly reduced compared to a group that was not treated with the composition containing sulfur, hesperidin, and succinic acid.

The cosmetic composition of the present invention can be manufactured into any formulation commonly manufactured in the art, and for example, can be formulated into a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation, and spray, but is not limited thereto. More specifically, it can be manufactured into the formulation of a flexible toner, a nourishing toner, a lotion, a nourishing cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray, or a powder.

The cosmetic composition of the present invention may include, in addition to the active ingredient, a carrier acceptable for use in cosmetic formulations. The term "acceptable carrier for use in cosmetic formulations" refers to an additional ingredient known and used to be capable of being included in cosmetic formulations, and which can improve the application of the active ingredient to the skin, user convenience, and preference without significantly reducing the primary efficacy of the active ingredient or causing adverse effects on the human body.

The carrier may be included in an amount of about 1 wt% to about 99.99 wt%, preferably about 50 wt% to about 99 wt%, of the total weight of the composition of the present invention. However, the content of the carrier may be appropriately adjusted depending on the formulation of the cosmetic, the specific application site, the desired application amount, etc., and is not particularly limited.

When the formulation of the present invention is a paste, cream, lotion, or gel, animal oil, vegetable oil, wax, paraffin, starch, tragacanth gum, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, or zinc oxide may be used as a carrier component.

When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and particularly in the case of a spray, a propellant such as chlorofluorohydrocarbon, propane/butane or dimethyl ether may be additionally included.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizer or emulsifier is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, 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 gum tragacanth, etc. can be used as a carrier component.

When the formulation of the present invention is a surfactant-containing cleansing agent, a fatty alcohol sulfate, a fatty alcohol ether sulfate, a sulfosuccinic acid monoester, an isethionate, an imidazolinium derivative, a methyl taurate, a sarcosinate, a fatty acid amide ether sulfate, an alkyl amidobetaine, a fatty alcohol, a fatty acid glyceride, a fatty acid diethanolamide, a vegetable oil, a lanolin derivative, or an ethoxylated glycerol fatty acid ester may be used as a carrier component.

The components included in the cosmetic composition of the present invention include, in addition to the active ingredient and the carrier component, components commonly used in cosmetic compositions, and may include conventional auxiliary agents such as antioxidants, stabilizers, solubilizers, vitamins, pigments, and fragrances.

The cosmetic composition of this example has a stable formulation with high dispersing power and can achieve an excellent skin improvement effect.

According to one aspect of the present invention, the present invention provides a pharmaceutical composition for preventing or treating acne, comprising sulfur, hesperidin, and succinic acid as active ingredients.

When the composition of the present invention is provided as a pharmaceutical composition, the pharmaceutical composition of the present invention may be prepared in unit dose form or may be prepared by inserting it into a multi-dose container by formulating it using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily performed by a person of ordinary skill in the art to which the present invention pertains. Specifically, for example, the excipients may additionally include a lubricant, a wetting agent, a sweetener, a flavoring agent, an emulsifier, a suspending agent, a preservative, etc.

According to a preferred embodiment of the present invention, the pharmaceutical composition of the present invention has a form of a topical skin formulation. The topical skin formulation is not particularly limited, but is preferably a powder, gel, ointment, cream, liquid, or aerosol formulation.

In the present invention, as a gel base material of a skin external preparation, one or more selected from among Carbopol, Carbomer, Polyethylene glycol, Polypropylene glycol, Polyacrylic acid, Carboxymethyl cellulose, Hydroxymethyl cellulose, Polyvinyl pyrrolidone, Gelatin, Alginate Salt, Chitin or Chitosan derivatives, hyaluronic acid, and collagen may be used, but is not limited thereto.

The appropriate dosage of the pharmaceutical composition of the present invention may be prescribed in various ways depending on factors such as the content of the active ingredient, the method of administration, the patient's age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity. Meanwhile, the dosage of the pharmaceutical composition of the present invention is preferably 0.001-100 mg/kg (body weight) per day, and the pharmaceutical composition of the above dosage can be applied locally or extensively in the form of an external skin formulation to the desired area, depending on the purpose of application.

According to one aspect of the present invention, an antibacterial composition for Cutibacterium acnes is provided, comprising sulfur, hesperidin, and succinic acid as active ingredients.

In the present invention, " Cutibacterium acnes (C. acnes )" is a gram-positive bacterium that resides in hair follicles and is one of the acne-causing bacteria. The lipolytic enzyme secreted by Cutibacterium acnes breaks down fatty acids secreted from sebaceous glands to form free fatty acids, stimulates hair follicles, and contributes to the inflammatory response of acne.

In the present invention, the term “antibacterial” means an activity that prevents or treats bacterial infection by inhibiting the growth or proliferation of bacteria including microorganisms.

The composition comprising the above sulfur, hesperidin, and succinic acid may have an antibacterial effect against Cutibacterium acnes.

In a specific embodiment of the present invention, the antibacterial activity of a composition comprising sulfur, hesperidin, and succinic acid against Cutibacterium acnes was tested, and it was confirmed that when the composition comprising sulfur, hesperidin, and succinic acid was treated, the growth of Cutibacterium acnes was inhibited and the bacterial count was reduced. Therefore, it was confirmed that the composition comprising sulfur, hesperidin, and succinic acid has specific antibacterial activity against Cutibacterium acnes strains.

According to one aspect of the present invention, the present invention provides a method for preparing a composition comprising sulfur, hesperidin, and succinic acid, comprising the following steps:

(a) a step of preparing a dispersion by dispersing sulfur in an aqueous solvent;

(b) a step of adding hesperidin and succinic acid to the dispersion obtained in step (a) and dissolving them; and

(c) A step of high-pressure dispersing the solution obtained in step (b).

In one embodiment of the present invention, the step (a) is dispersed using ultrasonication.

In one embodiment of the present invention, step (a) is performed for 0.5 to 5 hours at a frequency of 1 kHz to 30 kHz. More specifically, the frequency may be, but is not limited to, 1 kHz to 30 kHz, 5 kHz to 30 kHz, 10 kHz to 30 kHz, 15 kHz to 30 kHz, 20 kHz to 30 kHz, 1 kHz to 25 kHz, 5 kHz to 25 kHz, 10 kHz to 25 kHz, 15 kHz to 25 kHz, 20 kHz to 25 kHz, 1 kHz to 20 kHz, 5 kHz to 20 kHz, 10 kHz to 20 kHz, or 15 kHz to 20 kHz.

In one embodiment of the present invention, the aqueous solvent is selected from the group consisting of water, propylene glycol, pentylene glycol, and butylene glycol.

In one embodiment of the present invention, step (b) is dissolved using a homogenizer.

In one embodiment of the present invention, step (b) is performed at a rotation speed of 1,000 rpm to 5,000 rpm for 0.5 to 5 hours. The rotation speed is more specifically 1,000 rpm to 5,000 rpm, 1,500 rpm to 5,000 rpm, 2,000 rpm to 5,000 rpm, 2,500 rpm to 5,000 rpm, 3,000 rpm to 5,000 rpm, 1,000 rpm to 4,500 rpm, 1,500 rpm to 4,500 rpm, 2,000 rpm to 4,500 rpm, 2,500 rpm to 4,500 rpm, 3,000 rpm to 4,500 rpm, 1,000 rpm to 4,000 rpm, 1,500 rpm to 4,000 rpm, 2,000 rpm to 4,000 rpm, It may be, but is not limited to, 2,500 rpm to 4,000 rpm, 3,000 rpm to 4,000 rpm, 1,000 rpm to 3,500 rpm, 1,500 rpm to 3,500 rpm, 2,000 rpm to 3,500 rpm, 2,500 rpm to 3,500 rpm, 3,000 rpm to 3,500 rpm, 1,000 rpm to 3,000 rpm, 1,500 rpm to 3,000 rpm, 2,000 rpm to 3,000 rpm, or 2,500 rpm to 3,000 rpm.

In one embodiment of the present invention, step (b) is performed at a temperature of 40°C to 90°C. The temperature is more specifically 40°C to 90°C, 45°C to 90°C, 50°C to 90°C, 55°C to 90°C, 60°C to 90°C, 65°C to 90°C, 70°C to 90°C, 75°C to 90°C, 80°C to 90°C, 40°C to 85°C, 45°C to 85°C, 50°C to 85°C, 55°C to 85°C, 60°C to 85°C, 65°C to 85°C, 70°C to 85°C, 75°C to 85°C, 80°C to 85°C, 40°C to 80°C, 45°C to 80°C, 50°C to 80°C, 55°C to 80°C, 60°C to 80°C, 65°C to It may be, but is not limited to, 80°C, 70°C to 80°C, or 75°C to 80°C.

In one embodiment of the present invention, step (c) is performed for 1 to 5 cycles at a pressure of 100 bar to 1,500 bar. The pressure is more specifically 100 bar to 1,500 bar, 200 bar to 1,500 bar, 300 bar to 1,500 bar, 400 bar to 1,500 bar, 500 bar to 1,500 bar, 600 bar to 1,500 bar, 700 bar to 1,500 bar, 800 bar to 1,500 bar, 900 bar to 1,500 bar, 1,000 bar to 1,500 bar, 100 bar to 1,400 bar, 200 bar to 1,400 bar, 300 bar to 1,400 bar, 400 bar to 1,400 bar, 500 bar to 1,400 bar, 600 bar to 1,400 bar, 700 bar to 1,400 bar, 800 bar to 1,400 bar, 900 bar to 1,400 bar, 1,000 bar to 1,400 bar, 100 bar to 1,300 bar, 200 bar to 1,300 bar, 300 bar to 1,300 bar, 400 bar to 1,300 bar, 500 bar to 1,300 bar, 600 bar to 1,300 bar, 700 bar to 1,300 bar, 800 bar to 1,300 bar, 900 bar to 1,300 bar, 1,000 bar to 1,300 bar, 100 bar to 1,200 bar, 200 bar to 1,200 bar, 300 bar to 1,200 bar, 400 bar to 1,200 bar, 500 bar to 1,200 bar, 600 bar to 1,200 bar, 700 bar to 1,200 bar, 800 bar to 1,200 bar, 900 bar to 1,200 bar, 1,000 bar to 1,200 bar, 100 bar to 1,100 bar, 200 bar to 1,100 bar, 300 bar to 1,100 bar, 400 bar to 1,100 bar, 500 bar to 1,100 bar, 600 bar to 1,100 bar, 700 bar to 1,100 bar, 800 bar to 1,100 bar, 900 bar to 1,100 bar, 1,000 bar to 1,100 bar, 100 bar to It may be, but is not limited to, 1,500 bar, 200 bar to 1,000 bar, 300 bar to 1,000 bar, 400 bar to 1,000 bar, 500 bar to 1,000 bar, 600 bar to 1,000 bar, 700 bar to 1,000 bar, 800 bar to 1,000 bar, or 900 bar to 1,000 bar.

The composition and method according to each aspect of the present invention described above relate to a composition comprising sulfur, hesperidin, and succinic acid as common active ingredients and a method for producing the composition, and the features, definitions, and limitations regarding the components common to each invention are commonly applicable to each invention.

As demonstrated in specific embodiments of the present invention, the composition of the present invention has the effect of suppressing sebum secretion by inhibiting sebum synthesis within pores. The sebum synthesis suppression effect is concentration-dependent of the composition comprising sulfur, hesperidin, and succinic acid.

In addition, the composition of the present invention has an effect of suppressing acne or inflammation production.

From the above results, it can be seen that the composition comprising sulfur, hesperidin, and succinic acid of the present invention helps improve or treat skin shine or acne caused by excessive sebum secretion.

In addition, the composition comprising sulfur, hesperidin, and succinic acid of the present invention has excellent dispersibility and formulation stability.

The features and advantages of the present invention are summarized as follows:

(a) The present invention provides a cosmetic for controlling sebum secretion or improving acne, comprising sulfur, hesperidin, and succinic acid as active ingredients.

(b) The present invention provides a pharmaceutical composition for preventing or treating acne, comprising sulfur, hesperidin, and succinic acid as active ingredients.

(c) The present invention provides an antibacterial composition for Cutibacterium acnes containing sulfur, hesperidin, and succinic acid as active ingredients.

(d) The present invention provides a method for preparing a composition comprising sulfur, hesperidin, and succinic acid.

(e) When using a composition comprising sulfur, hesperidin, and succinic acid of the present invention as active ingredients, excessive sebum production can be suppressed and excessive sebum production can be controlled. In addition, the composition comprising sulfur, hesperidin, and succinic acid of the present invention as active ingredients has an excellent antibacterial effect against C. acnes , an acne-causing bacteria, and thus can be usefully used as an acne-improving functional cosmetic and an acne treatment product containing the same.

Figure 1 shows the results of a comparison of stability according to the method of dispersing a colloidal sulfur complex.
Figure 2 shows the results of measuring the mRNA expression level of ACC in sebum cells induced to produce excessive sebum by DHT following treatment with a colloidal sulfur complex.
Figure 3 shows the results of measuring the mRNA expression level of FAS in sebum cells induced to produce excessive sebum by DHT following treatment with a colloidal sulfur complex.
Figure 4 shows the results of measuring the mRNA expression level of AR in sebum cells induced to produce excessive sebum by DHT following treatment with a colloidal sulfur complex.
Figure 5 shows the effect of colloidal sulfur complex on improving keratin in human skin compared to the conventional one.
Figure 6 shows an image of the keratin area according to treatment with a colloidal sulfur complex and a colloidal sulfur complex on human skin.
Figure 7 shows the results of measuring the mRNA expression level of TLR-2 in sebaceous cells induced by LPS following treatment with a colloidal sulfur complex.
Figure 8 shows a control image of the Cutibacterium acnes antibacterial activity test.
Figure 9 shows an image of a test specimen for the Cutibacterium acnes antibacterial activity test.
Figure 10 shows the results of confirming the dispersion stability of the essence cosmetic composition applying Example 1 and Comparative Example 1 according to the present invention.
Figure 11 shows the results of confirming the accelerated stability of the essence cosmetic composition applying Example 1 and Comparative Example 1 according to the present invention.

Hereinafter, the present invention will be described in more detail through examples. These examples are intended solely to illustrate the present invention more specifically, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples, in accordance with the gist of the present invention.

Throughout this specification, “%” used to indicate the concentration of a particular substance is (weight/weight) % for solid/solid, (weight/volume) % for solid/liquid, and (volume/volume) % for liquid/liquid, unless otherwise stated.

Example

Example 1: Preparation of colloidal sulfur complex

The present inventors prepared a colloidal sulfur complex to develop a cosmetic composition for improving acne, which contains a colloidal sulfur complex as an active ingredient.

Specifically, 300 g of 1,3-butylene glycol was added to 50 g of colloidal sulfur, and primary dispersion was performed under ultrasonic conditions of 20 kHz, 1 hour. The primary dispersion was stirred using a mechanical homogenizer at 80°C to 90°C at 4,000 rpm, while 649 g of purified water was slowly added, and 0.5 g of hesperidin and 0.5 g of succinic acid were added and additionally dissolved for 1 hour. The solution was cycled three times at 1,000 bar using a high-pressure disperser (microfluidizer), and then filtered through 150 mesh to prepare a colloidal sulfur complex. The component contents of the colloidal sulfur complex are shown in Table 1.

Ingredient name Content (%) Purified water 64.9% 1,3-Butylene Glycol 30.0% Colloidal Sulfur 5.0% Hesperidin 0.05% Succinic acid 0.05%

Comparative Example 1: Colloidal sulfur complex without using ultrasonic or high-pressure disperser

In order to compare the stability of the colloidal sulfur complex according to the dispersion method, the inventors prepared Comparative Example 1 in the same manner as Example 1 except for using the ultrasonic and high-pressure disperser.

Specifically, 649 g of purified water and 300 g of 1,3-butylene glycol were added to 50 g of colloidal sulfur, 0.5 g of hesperidin, and 0.5 g of succinic acid, and the mixture was dissolved using a homogenizer at 80°C to 90°C and then filtered through 150 mesh to prepare Comparative Example 1.

Comparative Example 2: Colloidal sulfur composite without using a high-pressure disperser

In order to compare the stability of the colloidal sulfur complex according to the dispersion method, the inventors prepared Comparative Example 2 in the same manner as Example 1 except for using the high-pressure disperser.

Specifically, 300 g of 1,3-butylene glycol was added to 50 g of colloidal sulfur, and primary dispersion was performed under ultrasonic conditions of 20 kHz, 1 hour. While stirring the primary dispersion using a mechanical homogenizer at 4,000 rpm at 80°C to 90°C, 649 g of purified water was slowly added, and 0.5 g of hesperidin and 0.5 g of succinic acid were added and additionally dissolved for 1 hour. The above solution was filtered through 150 mesh to prepare Comparative Example 2.

The stability comparison results according to the manufacturing methods of Example 1, Comparative Examples 1 and 2 are shown in Fig. 1.

As shown in Fig. 1, it was confirmed that Example 1 had the most stable formulation when prepared compared to Comparative Example 1, which was dissolved using a homogenizer at high temperature, and Comparative Example 2, which was dissolved using ultrasound and a homogenizer but did not use a high-pressure disperser.

Comparative Example 3: Colloidal sulfur without hesperidin and succinic acid added

In order to compare the efficacy of colloidal sulfur complexes, the present inventors prepared Comparative Example 3, which was dispersed and prepared using the same manufacturing method as Example 1, but without adding hesperidin and succinic acid.

300 g of 1,3-butylene glycol was added to 50 g of colloidal sulfur, and primary dispersion was performed under ultrasonic conditions of 20 kHz, 1 hour. The primary dispersion was dissolved by slowly adding 649 g of purified water while stirring the dispersion using a mechanical homogenizer at 4,000 rpm at 80°C to 90°C. The solution was cycled 3 times at 1,000 bar using a high-pressure disperser, and then filtered through 150 mesh to prepare Comparative Example 3.

The results of the anti-oily efficacy test of Example 1, Comparative Example 3, the hesperidin treatment group, and the succinic acid treatment group are shown in Table 2.

sample density(%) DHT treatment Average amount of sebum (%) standard deviation standard error P-value Normal skin - 100.0 0.00 0.00 1.0000 Oily skin + 187.8 6.76 3.90 0.0000 salicylic acid 500 μg/ml - 95.6 6.69 3.86 0.3138 Example 1 1% + 183.2 8.85 5.11 0.0001 2% + 102.8 8.32 4.80 0.5905 3% + 65.2 2.20 1.27 0.0000 Comparative Example 3 1% + 192.7 9.24 3.74 0.0004 2% + 148.2 8.38 4.96 0.6871 3% + 109.4 4.12 2.12 0.0000 Hesperidin 0.05% + 174.3 6.43 3.72 0.4321 Succinic acid 0.05% + 161.8 8.96 6.93 0.0143

As shown in Table 2, it was confirmed that the sample manufactured by the method of Example 1 had superior sebum suppression ability compared to Comparative Example 3 without adding hesperidin and succinic acid, and it was confirmed that the sebum suppression ability was superior in Example 1 compared to the hesperidin and succinic acid treated group.

Therefore, these results indicate that the colloidal sulfur complex exhibits a higher sebum suppression ability through a synergistic effect compared to the colloidal sulfur, hesperidin, and succinic acid treatment groups alone.

Experimental Example 1: Pore Care: Anti-Oil Efficacy Test - Confirmation of ACC (Acetyl-coenzyme A carboxylase) mRNA Expression

In order to confirm the inhibitory effect of colloidal sulfur complex on the sebum biosynthesis-related gene ACC, the present inventors used real-time PCR to confirm the mRNA expression level of ACC according to treatment with colloidal sulfur complex.

Specifically, human sebocytes were seeded on a 60 mm plate and cultured for 24 hours in a 37°C, 5% _CO2 incubator. After that, the cultured cell medium was replaced with serum-free medium (DMEM/Ham's F12 1:1 (gibco)), and the cells were treated with the sample and cultured for 24 hours (37°C, 5% _CO2 incubator). Dihydrotestosterone (DHT) was used as an inducer that induces excessive sebum production. The cultured cells were collected with QIAzol ^TM Lysis Reagent (Qiagen), and RNA was isolated according to the manufacturer's method. The isolated RNA was quantified, cDNA was synthesized, and real-time PCR was performed.

The results are shown in Fig. 2 and Table 3.

sample density(%) DHT treatment ACC gene expression level (%) standard deviation standard error P-value Normal skin - 100.0 0.00 0.00 1.0000 Oily skin + 153.9 6.20 3.58 0.0001 Example 1 1% + 142.9 9.31 5.37 0.0031 2% + 106.6 6.72 3.88 0.1650 3% + 79.5 10.38 5.99 0.0269 Comparative Example 3 1% + 148.4 4.86 3.34 0.0012 2% + 121.7 8.72 6.54 0.0754 3% + 98.3 11.27 4.97 0.0464 Hesperidin 0.05% + 131.7 5.43 3.29 0.0012 Succinic acid 0.05% + 129.4 7.10 4.62 0.0894

As shown in Figure 2 and Table 3, ACC inhibition efficacy was observed at concentrations of 2% or higher of colloidal sulfur complex, reaching levels comparable to those of normal skin (untreated group) following DHT induction. Furthermore, the ACC inhibition efficacy of the colloidal sulfur complex was superior to that of the colloidal sulfur, hesperidin, and succinic acid groups treated alone.

Therefore, these results indicate that the colloidal sulfur complex can effectively inhibit ACC through a synergistic effect compared to the group treated with colloidal sulfur, hesperidin, and succinic acid alone.

Colloidal sulfur complex has been shown to effectively inhibit DHT-induced ACC, thereby regulating excessive sebum production caused by hormonal imbalance.

Experimental Example 2: Pore care: Anti-oil efficacy test - FAS (fatty acid synthase) mRNA expression

To confirm the ability of the colloidal sulfur complex to regulate excessive sebum production, the inventors induced overexpression of the fatty acid synthase FAS and confirmed the mRNA expression level of FAS according to treatment with the colloidal sulfur complex using real-time PCR.

Specifically, human sebocytes were seeded on a 60 mm plate and cultured for 24 hours in a 37°C, 5% _CO2 incubator. After culture, the cultured cell medium was replaced with serum-free medium (DMEM/Ham's F12 1:1 (gibco)), and the cells were treated with the sample and cultured for 24 hours (37°C, 5% _CO2 incubator). DHT was used as an inducer that induces excessive sebum production. The cultured cells were collected with QIAzol ^™ Lysis Reagent (Qiagen), and RNA was isolated according to the manufacturer's method. The isolated RNA was quantified, cDNA was synthesized, and real-time PCR was performed.

The results are shown in Fig. 3 and Table 4.

sample density(%) DHT treatment FAS gene expression level (%) standard deviation standard error P-value Normal skin - 100.0 0.00 0.00 1.0000 Oily skin + 187.8 6.76 3.90 0.0000 salicylic acid 500 μg/ml + 95.6 6.69 3.86 0.3138 Example 1 1% + 183.2 8.85 5.11 0.0001 2% + 102.8 8.32 4.80 0.5905 3% + 65.2 2.20 1.27 0.0000 Comparative Example 3 1% + 175.2 6.86 4.41 0.0012 2% + 134.7 7.64 6.56 0.0659 3% + 112.2 9.42 5.94 0.0145 Hesperidin 0.05% + 148.6 2.94 3.21 0.0265 Succinic acid 0.05% + 154.7 6.48 4.84 0.1485

As shown in Figure 3 and Table 4, the increased FAS induced by DHT showed a marked decrease similar to the level of normal skin (untreated group) from 2% concentration or higher of the colloidal sulfur complex. In addition, it was confirmed that the level of FAS expression was markedly reduced in the colloidal sulfur complex treatment group compared to the group treated with colloidal sulfur, hesperidin, and succinic acid alone.

Therefore, the colloidal sulfur complex treatment group can effectively inhibit FAS expression through a synergistic effect compared to the colloidal sulfur, hesperidin, and succinic acid treatment groups.

Based on these results, it is believed that colloidal sulfur complex can be used as a raw material that can control excessive sebum production and keep pores clean and healthy.

Experimental Example 3: Pore care: Anti-oil efficacy test - AR mRNA expression

In order to confirm the sebum control effect of the colloidal sulfur complex through inhibition of androgen receptor (AR) expression, the inventors of the present invention used real-time PCR to confirm the mRNA expression level of AR according to treatment with the colloidal sulfur complex.

Specifically, human sebocytes were seeded on a 60 mm plate and cultured for 24 hours in a 37°C, 5% _CO2 incubator. After culture, the cultured cell medium was replaced with serum-free medium (DMEM/Ham's F12 1:1 (gibco)), and the cells were treated with the sample and cultured for 24 hours (37°C, 5% _CO2 incubator). DHT was used as an inducer that induces excessive sebum production. The cultured cells were collected with QIAzol ^™ Lysis Reagent (Qiagen), and RNA was isolated according to the manufacturer's method. The isolated RNA was quantified, cDNA was synthesized, and real-time PCR was performed.

The results are shown in Fig. 4 and Table 5.

sample density(%) DHT treatment AR gene expression level (%) standard deviation standard error P-value Normal skin - 100.0 0.00 0.00 1.0000 Oily skin + 186.8 21.86 12.62 0.0023 salicylic acid 500 μg/ml + 92.2 13.93 8.04 0.3686 Example 1 1% + 184.8 8.84 5.11 0.0001 2% + 159.4 9.12 5.27 0.0004 3% + 87.3 10.61 6.13 0.1063 Comparative Example 3 1% + 185.4 10.24 5.67 0.0418 2% + 167.5 9.39 7.91 0.1943 3% + 142.7 11.75 4.82 0.0189 Hesperidin 0.05% + 137.2 6.38 4.35 0.0215 Succinic acid 0.05% + 146.8 August 19 6.75 0.0098

As shown in Table 5 and Figure 4, DHT-induced AR expression was significantly reduced at a 3% concentration of the colloidal sulfur complex. Furthermore, the colloidal sulfur complex treatment group demonstrated superior AR expression inhibition efficacy compared to the colloidal sulfur, hesperidin, and succinic acid treatment groups alone.

Therefore, these results indicate that colloidal sulfur complexes exhibit a marked sebum-regulating effect by inhibiting the early pathway (AR-mediated signaling) of DHT to its receptor AR.

Experimental Example 4: Pore Care: Skin Exfoliation Test - Clinical (Human Skin Brief Clinical Evaluation)

In order to confirm the keratin improvement efficacy of the colloidal sulfur complex at the clinical level, the inventors of the present invention conducted a simple clinical evaluation by applying the colloidal sulfur complex to human skin of three female subjects aged 32 years (±4.5 years).

Specifically, tape stripping was performed using a tape (B-squam tape) to collect keratin from an area with a lot of keratin (inner forearm), and the keratin collected before and after application of the colloidal sulfur complex was compared. The keratin was enlarged and photographed (×200 magnification) using a skin scope (Moritex, Japan), and the area of keratin was quantified using the Image J program.

The results are shown in Fig. 5, Fig. 6, and Table 6.

Sample Application Keratinous surface area Percent (%) Vehicle Before 165.006 100 After 126.66 76.76 Colloidal sulfur complex 5% Before 169.46 100 After 73.48 43.36

As shown in Figures 5, 6, and Table 6, when treating with a colloidal sulfur complex, a 43.5% reduction was observed compared to the vehicle type. The improvement rate compared to the vehicle type was calculated as follows.

Improvement rate compared to the public offering (%) = (76.76/76.76*100)-(43.36/76.76*100)

(The keratin area of 76.76% of the sample is set as 100%, and the calculation is made for the keratin area of 43.36% after sample processing)

Therefore, based on these results, the colloidal sulfur complex is judged to be a raw material with the ability to improve keratin.

Experimental Example 5: Anti-acne efficacy test - TLR-2 mRNA expression

In order to confirm the anti-acne efficacy of the colloidal sulfur complex through inhibition of TLR-2 (Toll-like receptor-2) expression, the inventors of the present invention used real-time PCR to confirm the mRNA expression level of TLR-2 according to treatment with the colloidal sulfur complex.

Specifically, human sebocytes were seeded on a 60 mm plate and cultured for 24 hours at 37°C, 5% _CO2 incubator. After culture, the cultured cell medium was replaced with serum-free medium (DMEM/Ham's F12 1:1 (gibco)), and the cells were treated with the sample and cultured for 24 hours (37°C, 5% _CO2 incubator). LPS was used as an inducer that causes overexpression of TLR-2. The cultured cells were collected with QIAzol ^™ Lysis Reagent (Qiagen), and RNA was isolated according to the manufacturer's method. The isolated RNA was quantified, cDNA was synthesized, and real-time PCR was performed.

The results are shown in Fig. 7 and Table 7.

sample density(%) LPS treatment TLR-2 gene expression level (%) standard deviation standard error P-value Normal skin - 100.0 0.00 0.00 1.0000 Oily skin + 167.8 12.42 7.17 0.0007 Example 1 1% + 140.5 15.54 8.97 0.0107 2% + 125.1 10.24 5.91 0.0133 3% + 87.5 6.31 3.64 0.0264 Comparative Example 3 1% + 153.7 August 16 5.90 0.0415 2% + 139.4 6.75 4.52 0.0115 3% + 117.5 12.73 8.77 0.1272 Hesperidin 0.05% + 153.8 10.68 7.38 0.0255 Succinic acid 0.05% + 132.1 7.96 5.99 0.1087

As shown in Figure 7 and Table 7, it was confirmed that the inhibitory effect of the colloidal sulfur complex at a concentration of 3% was shown for TLR-2 overexpressed by LPS induction, reaching the level of the untreated group. In addition, it was confirmed that the expression level of TLR-2 was significantly reduced in the colloidal sulfur complex treatment group compared to the group treated with colloidal sulfur, hesperidin, and succinic acid alone.

Therefore, the colloidal sulfur complex is considered to be a raw material with anti-acne efficacy that can suppress the formation of inflammatory acne by inhibiting the expression of TLR-2 induced by LPS.

Experimental Example 6: Cutibacterium acnes Antibacterial activity test for

In order to confirm the antibacterial effect of a colloidal sulfur complex against Cutibacterium acnes , the inventors measured the bacterial reduction rate according to treatment with the colloidal sulfur complex.

Specifically, Cutibacteria acnes strains were cultured in 5% blood TSA at 37°C under anaerobic conditions for 5 days. The culture conditions for C. acnes are shown in Table 8.

Culture conditions Strain name Culture conditions Waiting conditions Incubation time badge Cutibacterium acnes 37℃ Anaerobic 5 days 5% blood TSA

The adjusted bacterial solution was added to the test group and the control group (peptone water), stirred for 10 seconds, and left at room temperature for 30 minutes. The supernatant was removed by centrifugation at 13,000 rpm for 2 minutes, and washed twice with PBS. The stock solution was serially diluted and inoculated onto media, and the CFU was counted to determine the bacterial reduction rate, which was calculated as follows.

Reduction rate (%) = {(number of inoculations - strain after time) / number of inoculations} × 100

The results are shown in Fig. 8, Fig. 9 and Table 9.

Test items Inoculum (CFU/mL) Result value (CFU/mL) Decrease rate (%) Antibacterial activity test: Cutibacterium acnes ATCC 6919 7.55×10 ⁴ 59 99.9

As shown in Figures 8 and 9, it was confirmed that C. acnes was significantly reduced in the test group compared to the control group. In addition, as shown in Table 9, the inoculum of 7.55×10 ⁴ CFU/mL was reduced to 59 CFU/mL, showing a reduction rate of 99.9%.

Therefore, colloidal sulfur complex is considered to be a raw material with anti-acne efficacy that can suppress acne bacteria.

Manufacturing Example 1: Manufacturing of cosmetics

1-1. Preparation of essence

An essence containing the colloidal sulfur complex of the present invention as an active ingredient was prepared according to the composition shown in Table 10 below.

Specifically, disodium EDTA, glycerin, propanediol, and sodium polyacryloyl dimethyl taurate were dispersed in purified water, heated to 70°C to 75°C, and stirred for 5 minutes in an azimuth mixer. 1,2-hexanediol and ethylhexylglycerin were added at 45°C, stirred for 3 minutes, and then cooled to 30°C. Thereafter, Example 1 and Comparative Example 1 were added, stirred for 3 minutes, and defoamed to prepare an essence formulation.

furtherance Formulation Example 1 Comparative formulation example 1 weight% Example 1 10 - Comparative Example 1 - 10 purified water Remaining amount Remaining amount glycerin 5 5 propanediol 2 2 1,2-hexanediol 2 2 Sodium polyacryloyldimethyltaurate 0.2 0.2 Ethylhexylglycerin 0.05 0.05 Disodium EDTA 0.02 0.02 total 100 100

Experimental Example 7. Evaluation of Dispersion Stability

In order to compare the dispersion state of the essence manufactured with the compositions of Formulation Example 1 and Comparative Formulation Example 1, the inventors evaluated the dispersion stability using the principle of multiple light scattering.

To quantify the dispersion stability, a particle size dispersity meter (Formulaction, Turbiscan) was used, and the dispersion state was compared after measuring the transmission and backscattering amount (flux, %).

Specifically, manufactured Formulation Example 1 and Comparative Formulation Example 1 were filled into a cylindrical glass vial, and then measured 577 times in total, once every 25 seconds for 4 hours at 40˚C, and the results of the measured transmittance and backscattering are shown in A and B of Fig. 10.

The X-axis of Fig. 10 represents the height of the measuring glass bottle, and the Y-axis represents the transmittance and backscattering values according to each height. The transmittance and backscattering values at a height of 30 mm measured over a 4-hour period were confirmed, and are shown in Table 11 below.

Transmittance (%) Backscatter (%) Formulation Example 1 88.701751 - Comparative formulation example 1 0.014685 25.117336

As shown in Figure 10 and Table 11, Comparative Formulation Example 1 had low transmittance and high backscattering, whereas Formulation Example 1 had high transmittance and showed an excellent effect of improving dispersion within the formulation.

Experimental Example 8. Acceleration Stability Evaluation

In order to confirm the stability of the essence formulations manufactured with the compositions of Formulation Example 1 and Comparative Formulation Example 1, the present inventors performed an accelerated stability evaluation to measure the degree of re-separation of the formulations under centrifugal force.

To evaluate the acceleration stability of the formulation, a LumiSizer Dispersion Analyzer, a device that analyzes the stability of samples under centrifugal force, was used, and the analysis was performed at 50°C for approximately 4 hours at 4000 rpm.

The degree of dispersion stability of the sample was expressed as an instability index, and the results of comparing and measuring the degree of dispersion stability between samples are shown in Figures 11A and B and Table 12.

Instability Index
(Instability Index) Formulation Example 1 0.280 Comparative formulation example 1 0.302

As shown in Fig. 11, in the case of Formulation Example 1, it was confirmed that the change in light transmittance due to centrifugal force was small, whereas in the case of Comparative Formulation Example 1, the change in light transmittance due to centrifugal force was large.

In addition, as shown in Table 12, the instability index of Formulation Example 1 was measured to be lower than that of Comparative Formulation Example 1.

These results indicate that Formulation Example 1 has relatively better stability.

Attach an electronic file of the sequence list

Claims (15)

A cosmetic composition for controlling sebum secretion or improving acne, comprising colloidal sulfur, hesperidin, and succinic acid as active ingredients.
A cosmetic composition characterized in that the colloidal sulfur, hesperidin, and succinic acid are dispersed through high-pressure dispersion.
delete A cosmetic composition, characterized in that in claim 1, the colloidal sulfur is included in a proportion of 0.001 wt% to 30 wt% based on the total weight of the composition.
A cosmetic composition characterized in that, in claim 1, the hesperidin is included in a ratio of 0.001 to 30 parts by weight per 100 parts by weight of colloidal sulfur.
A cosmetic composition according to claim 1, characterized in that the succinic acid is included in a ratio of 0.001 to 30 parts by weight per 100 parts by weight of colloidal sulfur.
A pharmaceutical composition for preventing or treating acne, comprising colloidal sulfur, hesperidin, and succinic acid as active ingredients,
A pharmaceutical composition characterized in that the colloidal sulfur, hesperidin, and succinic acid are dispersed through high pressure dispersion.
An antibacterial composition for Cutibacterium acnes comprising colloidal sulfur, hesperidin, and succinic acid as active ingredients,
An antibacterial composition characterized in that the colloidal sulfur, hesperidin, and succinic acid are dispersed through high-pressure dispersion.
A method for preparing a composition comprising colloidal sulfur, hesperidin, and succinic acid, comprising the following steps:
(a) a step of preparing a dispersion by dispersing colloidal sulfur in an aqueous solvent;
(b) a step of adding hesperidin and succinic acid to the dispersion obtained in step (a) and dissolving them; and
(c) A step of high-pressure dispersing the solution obtained in step (b).
A manufacturing method characterized in that, in the 8th paragraph, step (a) disperses using ultrasonication.
A manufacturing method, characterized in that in claim 9, step (a) is performed for 0.5 to 5 hours at a frequency of 1,000 Hz to 30,000 Hz.
A manufacturing method in claim 8, wherein the aqueous solvent is at least one aqueous solvent selected from the group consisting of water, propylene glycol, pentylene glycol, and butylene glycol.
A manufacturing method characterized in that, in the 8th paragraph, step (b) dissolves using a homogenizer.
A manufacturing method, characterized in that in claim 12, step (b) is performed at a rotation speed of 1,000 rpm to 5,000 rpm for 0.5 to 5 hours.
A manufacturing method, characterized in that in claim 8, step (b) is performed at 40°C to 90°C.
A manufacturing method, characterized in that in claim 8, step (c) is performed for 1 to 5 cycles at a pressure of 100 bar to 1,500 bar.