KR20200025429A - Composition for preventing or treating acne comprising ethyl acetate fraction of sargassum miyabei yendo - Google Patents

Abstract

The present invention relates to a composition for preventing or treating acne containing a Sargassum miyabei ethyl acetate fraction as an active component. The Sargassum miyabei ethyl acetate fraction exhibits an effect of inhibiting the penetration of neutrocytes induced by Propionibacterium acnes, which is acne-causing bacteria, and reducing abscess. Therefore, the composition containing the Sargassum miyabei ethyl acetate fraction as the active component can be provided as an excellent acne therapeutic agent and a cosmetic composition for preventing or alleviating acne.

Description

Composition for preventing or treating acne comprising ethyl acetate fraction of sargassum miyabei yendo}

The present invention relates to a pharmaceutical composition and a cosmetic composition for acne prevention or treatment containing the miabemosaban ethyl acetate fraction as an active ingredient.

The cause of acne is still not clearly defined, but three genetic causes are reported to be directly involved in acne outbreaks when genetic and environmental factors are excluded. The three important causes of the acne pathology briefly described as follows.

The first cause may be due to excessive secretion of sebum. The formation of sebum is caused by the action of androgen hormones, and the abnormal increase of the male hormone or various mechanisms associated with it promotes sebaceous gland function, resulting in excess sebum.

The second is explained by the closure of the pores due to hyperkeratinization of the hair follicles. The produced sebum should be discharged smoothly out of the skin, but the pores are blocked due to the exaggeration of the hair follicles, thereby suppressing the smooth discharge of sebum, and consequently, the sebum is stagnated in the hair follicles to form microsurface. In connection with sebaceous secretion, all the enzymes necessary to convert inactive steroid precursors to active androgens are present in the skin, 5α-reductase being one of them. Testosterone, one of the male hormones, enters the sebaceous gland and is converted to dihydrotestosterone by 5α-reductase present in the cells, which signals a multistage pathway. To produce sebum as a result.

The third cause is due to acne lesions such as Staphylococcus epidermis, Staphylococcus aureus and Propionibacterium acnes that cause acne. It is explained as an important cause of deterioration. Acne bacteria residing in hair follicles form a pore wall irritant. The microvesicles gradually increase in size as the sebum continues to grow and develop into a cotton wool. As a result, the hair follicle wall becomes thinner, and the irritant produced by acne bacteria stimulates the thinned hair follicle wall, which gradually deteriorates the cotton wool into inflammatory lesions. (Pain → pustules → nodule → scar). Meanwhile, according to the causes of acne, various studies on methods for treating or improving acne have been performed, focusing on sebum suppression and antibacterial effect on skin flora.

Acne treatment drugs known to date are useful for the treatment of acne by controlling sebum secretion, correcting keratinization process, inhibiting the bacteria represented by propionibacterium acnes, and at least one of these three roles. Specifically, the use of female hormones, such as anti-androgens to control the secretion of abnormal male hormones to suppress sebaceous hypersecretion, the use of antibacterial and antibiotics to inhibit the growth of acne bacteria, non-steroidal anti-inflammatory A method of using an anti-inflammatory agent has been used, and in the cosmetic field, a method of inhibiting skin exfoliation and acne bacteria by adding components such as resorcinol, sulfur, salicylic acid and benzoyl peroxide has been mainly used.

However, when these ingredients are added excessively, skin irritation and easily dry side effects occur. Therefore, the compounding limit for resorcinol and salicylic acid is determined, and components such as benzoyl peroxide are designated as prohibited ingredients in Korea. .

Republic of Korea Patent Publication No. 10-2004-0056080 (Published June 30, 2004)

The present invention is to provide a composition for preventing or treating acne containing a natural product miabemozaban as an active ingredient while preventing acne induced by acne causing bacteria and showing an excellent therapeutic effect.

The present invention provides a pharmaceutical composition for preventing or treating acne, which contains Miabemozaban ethyl acetate fraction as an active ingredient.

In another aspect, the present invention provides a cosmetic composition for preventing or improving acne containing miabemosaban ethyl acetate fraction as an active ingredient.

According to the present invention, the miabemozaban ethyl acetate fraction has been found to exhibit an effect of inhibiting the infiltration of neutrophils induced by the acne-causing bacteria propionibacterium acnes and reducing the abscess. The composition containing the fraction as an active ingredient may be provided as an excellent acne treatment and a cosmetic composition for preventing or improving acne.

1 is a schematic diagram showing a lesion site in which the acne bacterium Propionibacterium acnes is injected, number 1 is a site in which saline is injected, and number 2 is Miabemozaban after injection of acne bacteria (PA). Ointment (vechile) without the ethyl acetate fraction is applied to the site, No. 3 is the site where the ointment containing 50μg of Miabemozaban ethyl acetate fraction (SMYEE) after injection of acne bacteria (PA) (PA: P. acnes ).
FIG. 2 is a hemotalk confirming changes in abscess formation after application of ointment containing 50 μg of Miabemozaban ethyl acetate fraction (SMYEE) to a lesion site injected with acne bacterium Propionibacterium acnes. Cylin & Eosin staining results.
3 is an immunity confirming the inhibitory effect of neutrophil infiltration after application of ointment containing 50 μg of Miabemozaban ethyl acetate fraction (SMYEE) to the lesion site injected with acne bacterium Propionibacterium acnes Histochemical staining results (PA: P. acnes, NIMP-R14: neutrophil markers).

Hereinafter, the present invention will be described in more detail.

Mia bemozaban (sargassum miyabei yendo) is a brown algae belonging to the genus Sargassaceae and sargassum, but inhabited mainly in the south coast and Jeju island in Korea, but its physiological activity is much less known than other genus. Accordingly, the present inventors completed the present invention, while studying the physiological activity of the mibemozaban, the miabemozaban showed an excellent effect on the treatment of acne induced by acne bacteria.

The present invention can provide a pharmaceutical composition for preventing or treating acne containing Mia bemozaban ethyl acetate fraction as an active ingredient.

The fraction may be a miabemozaban ethyl acetate fraction obtained by dividing the miabemosaban ethanol extract with ethyl acetate, and more preferably, may be an ethyl acetate fraction of the miabemosaban extract extracted with an aqueous 70% ethanol solution.

The miabemozaban ethyl acetate fraction can inhibit abscess formation or neutrophil infiltration induced by acne bacteria.

The acne may be induced by acne-induced skin flora, which is composed of Staphylococcus epidermis, Staphylococcus aureus, and Propionibacterium acnes. Preferably it may be one induced by Propionibacterium acnes (Propionibacterium acnes).

The pharmaceutical composition may be an external preparation for skin.

In more detail, the external skin preparation may be selected from the group consisting of ointments, creams, lotions, solutions, dressings, patches, blisters, tapes, aerosols, external preparations and sprays.

In another embodiment of the present invention, the pharmaceutical composition containing the miabemosaban ethyl acetate fraction as an active ingredient is a suitable carrier, excipient, disintegrant, sweetener, coating agent, swelling agent, lubricant, lubricant, commonly used in the preparation of the pharmaceutical composition. It may further comprise one or more additives selected from the group consisting of flavours, antioxidants, buffers, bacteriostatics, diluents, dispersants, surfactants, binders and lubricants.

Specifically, the carriers, excipients and diluents are lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline Cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil can be used, and solid preparations for oral administration include tablets, pills, powders, granules, capsules. And the like, and such solid preparations may be prepared by mixing at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin, and the like in the composition. In addition to simple excipients, lubricants such as magnesium styrate and talc may also be used. Oral liquid preparations include suspensions, solutions, emulsions, syrups, and the like, and may include various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories, and the like. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As a base material of suppositories, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

According to one embodiment of the invention the pharmaceutical composition is intravenous, intraarterial, intraperitoneal, intramuscular, intraarterial, intraperitoneal, intrasternal, transdermal, nasal, inhaled, topical, rectal, oral, intraocular or intradermal Via the route can be administered to the subject in a conventional manner.

The preferred dosage of the Miabemozaban ethyl acetate fraction may vary depending on the condition and weight of the subject, the type and extent of the disease, the drug form, the route of administration and the duration and may be appropriately selected by those skilled in the art. According to one embodiment of the present invention, but not limited thereto, the daily dosage may be 0.01 to 200 mg / kg, specifically 0.1 to 200 mg / kg, more specifically 0.1 to 100 mg / kg. Administration may be administered once a day or divided into several times, thereby not limiting the scope of the invention.

In the present invention, the 'subject' may be a mammal including a human, but is not limited thereto.

In addition, the present invention can provide a cosmetic composition for preventing or improving acne containing miabemosaban ethyl acetate fraction as an active ingredient.

The cosmetic composition may include stabilizers, solubilizers, conventional auxiliaries such as vitamins, pigments and flavors, and a carrier, in addition to the fraction of miabemosaban ethyl acetate as an active ingredient.

The cosmetic composition may be prepared in any formulation conventionally prepared in the art, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, oils, powder foundations, emulsion foundations, It may be formulated as a wax foundation and spray, but is not limited thereto. More specifically, it may be prepared in the form of a sun cream, a flexible lotion, a convergent lotion, a nourishing lotion, a nourishing cream, a massage cream, an essence, an eye cream, a pack, a spray or a powder.

When the formulation is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicon, bentonite, silica, talc or zinc oxide may be used as a carrier component. .

If the formulation is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used, especially in the case of a spray, additionally chlorofluorohydrocarbon, propane / butane Or propellants such as dimethyl ether.

If the formulation is a solution or emulsion, solvents, solubilizers or emulsions are used as carrier components, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3 Fatty acid esters of butylglycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan.

When the formulation is a suspension, liquid carrier diluents such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose , Aluminum metahydroxy, bentonite, agar or tracant and the like can be used.

Hereinafter, examples will be described in detail to help understand the present invention. However, the following examples are merely to illustrate the content of the present invention is not limited to the scope of the present invention. The embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art.

< Example  1> Mia bemozaban  Ointment manufacturers

One. Mia bemozaban  Ethyl acetate ( Sargassum miyabei Yendo  ethyl acetate; SMYEE) Fraction  Ready

70% ethanol extract of Mia bemozaban was concentrated in a reduced pressure concentrator, and distilled water was added and suspended at 60 ° C for 1 hour. Thereafter, the 70% ethanol suspension of Mia bemozaban was placed in a separatory funnel for fractionation by solvent polarity, and then hexane in a 1: 1 ratio was sufficiently shaken and left at room temperature for 3 hours. After 3 hours, the layers were separated and the hexane layer was removed from the upper layer and concentrated by a vacuum concentrator to complete the hexane fraction. This process was repeated three times.

After decanting the hexane layer, chloroform, which is the next polar solvent, was added to the remaining distilled water layer, sufficiently shaken, and left at room temperature for 3 hours. After 3 hours, the layers were separated and the chloroform layer in the lower layer was taken out and concentrated in a reduced pressure concentrator to complete the chloroform fraction. The above procedure was repeated three times.

After decanting the chloroform layer, ethyl acetate, the next polar solvent, was added to the remaining distilled water layer, shaken sufficiently, and left at room temperature for 3 hours. After 3 hours, the layers were separated and the ethyl acetate layer in the upper layer was concentrated in a vacuum concentrator. To obtain an ethyl acetate fraction, which was repeated three times.

2. Mia bemozaban  Ointment manufacturers

The ointment containing the miabemosaban ethyl acetate fraction (SMYEE) fractionated in the above procedure was prepared.

0.4 mL of SMYEE stock (25 mg / mL in 70% ethanol) and 1.3 mL of distilled water were placed in beaker A and heated in a beaker with water maintained at a temperature of 60-70 ° C ..

In addition, 0.22 g of oily jojoba oil was added to an emulsifier in which 0.04 g of an emulsion pile and 0.04 g of an olive oil were mixed in a beaker B, and heated to a temperature of 60 to 70 ° C. by a hot water method while stirring using a magnetic bar.

When the jojoba oil and emulsifier were dissolved and mixed, a solution of beaker A containing SMYEE was added to beaker B, and the stirring speed was maximized and mixed for 5 seconds.

After cooling with slow stirring to confirm the solidified concentration, 20 μl of natural preservatives were added and mixed well, and then stored in a suitable container and refrigerated.

In addition, as a control, 0.4 mL of 70% ethanol was added instead of the miabemosaban ethyl acetate fraction (SMYEE) to prepare an ointment containing no SMYEE in the same manner as above.

Example (5 mg / mL) Comparative example Composition SMYEE stock 0.4 mL 0.4 mL of 70% ethanol 1.3 mL of distilled water 0.22 g oil-based jojoba oil Emulsifying wax 0.04g Olive Oil 0.04g Final volume 2 mL 2 mL

< Example  2> Check the anti acne effect

1. Making Acne Animal Models

1 × 10 ⁶ by using the sterilization in each of the two parts (2 and 3), the syringe as shown in Figure 1 by three equal parts after epilation the whole is allowed to stand for 24 hours after a stabilization period has passed from the lower end of the ear such as a mouse to tail upper end Acne was induced by injecting CFUs / 10 μL of propionibacterium acnes (P.acnes) acne bacteria, and 4 days later, the inflammatory state of the mouse skin was confirmed.

2. Mia bemozaban  Confirmation of inflammation size change by applying ointment

After 4 days of acne bacteria injection, the ointment containing no control Miabemozaban ethyl acetate fraction (SMYEE) was applied twice a day for 4 days to the area 2 of the skin such as a mouse, and the ointment containing 50 μg of SMYEE was applied to the control group. The same method was applied to skin 3 of the mouse and the like, and the size of the abscess induced by P.acnes was visually observed.

As a result, there was no decrease in the inflammatory response in the control group of the second site to which the ointment containing SMYEE was not applied, whereas the abscess size was remarkably decreased in the third site to which the ointment containing the SMYEE was applied. .

3. Histopathology Histopathological ) analysis

Four days after the application of ointment, three parts of skin tissues were extracted from a mouse acne animal model. Each extracted skin tissue was fixed in 10% formalin and then embedded in paraffin embedding through a series of tissue treatment procedures.

Tissue sections prepared by cutting paraffin-embedded tissues to a thickness of 4 μm were stained with hematoxylin & eosin, and the tissues were observed under an optical microscope.

As a result, as shown in FIG. 2, the abscess formation of skin tissue 3 coated with the SMYEE-containing ointment was significantly suppressed than the skin tissue coated 2 with the SMYEE-free ointment.

4. Immunohistochemical Staining Analysis

Four days after the application of ointment, three parts of skin tissues were extracted from a mouse acne animal model. Each extracted skin tissue was fixed in 10% formalin and then embedded in paraffin embedding through a series of tissue treatment procedures.

Tissue sections slides prepared by cutting paraffin-embedded tissues to a thickness of 4 μm were subjected to immunochemical staining with neutrophil specific antibodies (NIMP-R14, neutrophil markers) to confirm the distribution of neutrophils.

As a result, it was confirmed that the number of neutrophils was increased in the tissue section of the second site injected with P. acnes, as shown in FIG. At the site, the neutrophil count was significantly reduced compared to the tissue at site 2 where ointment containing SMYEE was not applied.

Having described the specific part of the present invention in detail, it is apparent to those of ordinary skill in the art that such a specific description is merely a preferred embodiment, thereby not limiting the scope of the present invention. something to do. Therefore, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

Claims (7)

A pharmaceutical composition for preventing or treating acne, which contains Miabemozaban ethyl acetate fraction as an active ingredient. The pharmaceutical composition for preventing or treating acne according to claim 1, wherein the fraction is obtained by fractionating Miabemozaban ethanol extract with ethyl acetate. The pharmaceutical composition for preventing or treating acne according to claim 1, wherein the miabemozaban ethyl acetate fraction inhibits abscess formation or neutrophil infiltration induced by acne bacteria. The method according to claim 1, wherein the acne is induced by acne-induced skin flora comprising Staphylococcus epidermis, Staphylococcus aureus and Propionibacterium acnes Pharmaceutical composition for the prevention or treatment of acne, characterized in that. The pharmaceutical composition for preventing or treating acne of claim 1, wherein the pharmaceutical composition is an external preparation for skin. The method for preventing acne according to claim 5, wherein the external skin preparation is selected from the group consisting of ointments, creams, lotions, liquids, dressings, patches, blisters, tapes, aerosols, external acids and sprays. Therapeutic pharmaceutical composition. Cosmetic composition for preventing or improving acne containing Miabemozaban ethyl acetate fraction as an active ingredient.

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