KR20110047692A - Composition for Reducing Skin Pore Size and Secreting Sebum Containing flower extract of Potentilla chinensis - Google Patents

Abstract

PURPOSE: A composition containing Potentilla chinensis extract for tightening pore or suppressing sebum secretion is provided to suppress SNARE(soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex formulation. CONSTITUTION: A composition for tightening pore or suppressing sebum contains Potentilla chinensis extract as an active ingredient. The composition suppresses membrane fusion between synaptic vesicle and presynaptic membrane. The Potentilla chinensis extract isolated using water, ethanol, or anhydrous methanol. A pharmaceutical composition or a cosmetic composition contains the composition. The cosmetic composition is manufactured in the form of astringent, lotion, massage cream, essence, cleansing cream, cleansing foam, cleansing water, pack, powder, body lotion, body cream, or body essence.

Description

Composition for Reducing Skin Pore Size and Secreting Sebum Containing flower extract of Potentilla chinensis}

The present invention relates to a composition for inhibiting pore reduction or sebum secretion, including the extract of Ulleungchae.

The pores are distributed throughout the facial skin, but the nose and cheek areas can be identified with the naked eye, and the appearance of the pores varies depending on the endogenous and exogenous factors such as sex, genetics, aging, acne and chronic UV exposure. The pores are widened because the sebum is excessively secreted or skin aging begins. As the collagen fibers and elastic fibers supporting the wall of the pores degenerate and decrease, the skin elasticity is lost and sagging.

On the other hand, since the contraction or relaxation of the muscles (hair muscles) attached to the hair is controlled by the sympathetic and parasympathetic nerves, the pores can be reduced or enlarged by neuromodulation. Sympathetic nerve is slightly away from the muscles pore shrinkage action, parasympathetic nerves are close to the muscles are pore enlargement action. Optionally, suppressing parasympathetic nerves causes the sympathetic nerve to act as a compensatory action, shrinking the muscles attached to the hair and shrinking the pores.

As described above, botulinum toxin is a substance that produces a desired effect by regulating stimulus transmission by nerves, for example, inhibits the release of neurotransmitters and causes convulsive paralysis of muscle cells. However, botulinum toxin is a kind of neurotoxin, known as one of the strongest toxins, and has an average lethal dose of about 1 / kg (intravenous injection), which is dangerous enough to mean that one teaspoon can kill 1.2 billion people. . Most of these botulinum toxin delivery methods are by injection technique, and inappropriate injection techniques can damage tissue and / or deliver botulinum toxin to an unintended and / or undesired location. In addition, in the area around the eyes, side effects such as lid and brow ptosis may occur, and pain, hematoma, ecchymosis and bruising may occur.

Therefore, the need has been discussed for the development of ingredients that are safe using natural materials that are both effective and nontoxic, and which are effective in reducing pore reduction or sebum secretion with fewer side effects.

The present invention aims to solve the technical problem that has been requested from the past. Specifically, an object according to an embodiment of the present invention is to provide a composition comprising as an active ingredient Ureungchae extract that has excellent pore shrinkage or sebum secretion inhibitory effect.

In accordance with this object, one embodiment of the present invention relates to a composition for inhibiting pore reduction or sebum secretion, which comprises the extract of Ulleungchae as an active ingredient.

One embodiment of the present invention relates to a pharmaceutical composition comprising the composition for inhibiting pore reduction or sebum secretion.

In addition, one embodiment of the present invention relates to a cosmetic composition comprising the composition for inhibiting pore reduction or sebum secretion.

The cosmetic composition according to the present invention includes the extract of Ulleungchae as an active ingredient, inhibits the formation of a complex of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE), and inhibits the release of neurotransmitters, thereby reducing pores or sebum. A secretory inhibitory effect can be exhibited.

The inventors of the present application test the membrane fusion inhibitory effect by the Ureungchae extract, it was confirmed that the Ureungchae extract as shown in the following examples can inhibit the formation of SNARE to exhibit a membrane fusion inhibitory effect. In addition, the results of the neurotransmitter release inhibitory effect by the Ureungchae extract, it was confirmed that it does not have the same toxicity as the botulinum toxin, it can be safe, but exhibit a similar neurotransmitter release inhibitory effect.

In one embodiment, the composition may inhibit the formation of a complex of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE), which may inhibit membrane fusion between synaptic vesicles and presynaptic membranes. have.

Specifically, when the neurotransmitter is discharged, the synaptic vesicle containing the neurotransmitter must be fused with the presynaptic membrane to form a pathway between the two boundaries. The protein that provides the cause of membrane fusion is three protein complexes called soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE), which open the pathway of neurotransmitter release by membrane fusion between synaptic vesicles and synaptic membranes. T-SNARE complexes attached to the target membrane and v-SNARE attached to the vesicles are involved. T-SNARE is a complex of a protein called syntaxin 1a and a protein called SNAP-25, which is twisted like a pretzel.

Normally, membrane fusion results in rearrangement of lipid bilayers. Since biofilms are strongly pushed against each other, these membranes are not spontaneously fused and have a strong force from the outside to overcome the repulsion between the membranes. At this time, it is SNARE protein that creates strong force enough to overcome the repulsion between membranes. The formation of SNARE complex is a key phenomenon of exocytosis that overcomes repulsion between membranes and releases neurotransmitters. Can be.

On the other hand, in order to control the relaxation and contraction of the muscle, there is a neuromuscular junction (neuromuscular junction) in the upper layer of the muscle, the nerve terminal (nerve terminal) is loaded with synaptic vesicles. Through the membrane fusion process by the SNARE protein as described above, the neurotransmitter in the synaptic vesicles loaded at the nerve terminal can be discharged to regulate the relaxation and contraction of the muscle.

In this regard, the Uiungreung extract of the present invention may inhibit membrane fusion by inhibiting the formation of the SNARE complex, and as a result, neuromuscular junctions of neurotransmitters, particularly acetylcholine, contained in synaptic vesicles of nerve endings. ) May inhibit release. As a result, nerve impulses may be disturbed and convulsive paralysis of muscle cells may occur. Through this process, the composition of the present invention can cause spasm of paralysis in the myoblasts around the pores, which can constrict pores.

The botulinum toxin mentioned in the background is a protease that cleaves SNARE protein, a key protein involved in neurotransmitter release, which blocks neurotransmission by cleaving SNARE protein, resulting in paralysis of botox-infused muscle cells. Thus, while blocking neurotransmission by irreversibly cleaving the SNARE protein, the composition according to the invention may be a competitive inhibitor that inhibits neurotransmission by inhibiting the formation of the SNARE complex.

In another embodiment, the Ureungchae extract of the present invention can regulate the release of catecholamine-based neurotransmitters such as adrenaline or noradrenaline to skin muscle cells. Catecholamines, such as adrenaline or noradrenaline, are stress hormones that are released during stress, causing skin irritation, inflammation, and loss of skin immune function, which can cause symptoms such as acne, seborrheic eczema, atopy, psoriasis, alopecia areata, stomatitis, and chronic hives. Ulleungchae extract of the present invention can prevent the sebum is excessively secreted or the skin aging begins to denature, decrease the collagen fibers and elastic fibers supporting the pores wall.

Potentilla chinensis, also called scabbard, belongs to rosaceae and is distributed in Korea, Japan, China, Taiwan, etc., and grows in fields, rivers, and beaches. Young leaves are edible, and in oriental medicine and folk, stems and leaves are harvested in spring and autumn and applied to the soles or dried and used for fever and diuresis.

The Ureungchae extract is not particularly limited, but may be a dry extract or a fraction of Potentilla chinensis extracted by a warm extraction method through at least one solvent selected from the group consisting of water, ethanol and anhydrous methanol, for example. have.

In one embodiment, the composition may comprise from 0.0001 to 30% by weight of active ingredient based on the total amount of the composition, and optionally from 0.001 to 10% or 0.01 to 2% by weight of active ingredient Can be.

When the content of the active ingredient is less than 0.0001% by weight based on the total amount of the composition, it is difficult to show efficacy, and when the amount exceeds 30% by weight based on the total amount of the composition, there may be a concern of side effects.

The present invention also relates to a cosmetic composition comprising a composition for inhibiting pore reduction or sebum secretion.

The cosmetic composition may be formulated as an external skin base applied to the skin, such as a transdermal dosage form such as cosmetics, and may be appropriately selected and blended with other ingredients to achieve a desired effect according to techniques conventional in the art.

The cosmetic form may be formed by containing a cosmetically or dermatologically acceptable medium or base. These are all formulations suitable for topical application, for example, emulsions, suspensions, microemulsions, microcapsules, microgranules or ionic (liposomes) obtained by dispersing the oil phase in solutions, gels, solids, pasty anhydrous products, aqueous phases, and It may be provided in the form of a nonionic vesicle dispersant or in the form of a cream, skin, lotion, powder, ointment, spray or cone stick.

The cosmetic composition may be prepared according to conventional methods in the art. The composition according to the invention can also be used in the form of a foam or in the form of an aerosol composition further containing a compressed propellant.

The cosmetic composition may be a fatty substance, an organic solvent, a dissolving agent, a thickening agent, a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, a surfactant, water, an ionic or nonionic emulsifier, Cosmetics or skin such as fillers, metal ion sequestrants, chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic actives, lipid vesicles or any other ingredients commonly used in cosmetics It may contain adjuvants commonly used in the scientific field. The adjuvant may be introduced in an amount generally used in the cosmetic or dermatology field.

The cosmetic composition is not particularly limited in the formulation, for example, supple cosmetics, astringent cosmetics, nourishing cosmetics, nutrition cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, It can be formulated into cosmetics such as packs, powders, body lotions, body creams, body oils and body essences. In some cases, the cosmetic composition may be applied in a form that is absorbed into the skin using a microneedle or the like.

The present invention also relates to a pharmaceutical composition comprising a composition for inhibiting pore reduction or sebum secretion.

The pharmaceutical composition may further contain pharmaceutical supplements such as preservatives, stabilizers, hydrating or emulsifying accelerators, salts and / or buffers for the control of osmotic pressure, and other therapeutically useful substances, and various oral methods according to conventional methods. It may be formulated in the form of a dosage form or parenteral dosage form.

The oral dosage forms include, for example, tablets, pills, hard and soft capsules, solutions, suspensions, emulsifiers, syrups, powders, powders, fine granules, granules, pellets, and the like. Active agents, diluents (e.g. lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and glycine), glidants (e.g. silica, talc, stearic acid and its magnesium or calcium salts and polyethylene glycols) have. Tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and polyvinylpyrrolidine, optionally starch, agar, alginic acid or its sodium salt Pharmaceutical additives such as disintegrants, absorbents, colorants, flavors, and sweeteners. The tablets can be prepared by conventional mixing, granulating or coating methods.

In addition, the parenteral administration agent may be, for example, formulations such as injections, drops, ointments, lotions, gels, creams, sprays, suspensions, emulsions, suppositories, and patches, but are not limited thereto. no.

Moreover, the pharmaceutical composition may be administered orally, parenterally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously, and the like. In some cases, the pharmaceutical compositions according to the invention may be administered topically, for example, to the facial skin.

Pharmaceutically acceptable doses, ie dosages, of the active ingredients will depend on the age, sex, and weight of the subject to be treated, the specific disease or pathology to be treated, the severity of the disease or pathology, the route of administration and the judgment of the prescriber. . The "pharmaceutically acceptable dose" refers to the amount generally applied in drug administration, and when used in such doses, is an amount that exerts efficacy at the active site of the subject without substantial severe toxicity, irritation, or allergic reactions. . Dosage determination based on these factors is within the skill of the art. Typical dosages can be from 0.01 mg / kg / day to 1000 mg / kg / day and from 1 mg / kg / day to 40 mg / kg / day, but the dosage limits the scope of the invention in any way. It is not.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the following Examples are provided to illustrate the present invention, and the scope of the present invention is not limited thereto.

Example 1 Preparation of Ulleungchae Extract

The manufacturing method of Ureungchae extract of the present invention is as follows. 1000 ml of anhydrous methanol was added to the natural product (100 g) purchased from the Plant Extract Bank (Daejeon, Korea) using an extractor equipped with a reflux condenser (Model: HB 4 basic, manufacturer: IKA) for 2 hours at 80 ° C. Warm extraction. The extract was filtered through Whatman No. 2 filter paper, and the remaining residue was extracted one or more times in the same manner as above, and the extracted extracts were combined under reduced pressure (model name: Rotavapor, manufacturer: Buchi, temperature: 40 ° C.). After lyophilization, a dry extract was obtained.

Test Example 1 Membrane Inhibition Effect

Membrane fusion inhibitory effect on Ulleungchae extract was tested. To produce SNARE proteins, SNAP25 (Synaptosomal-associated protein 25: NM011428), Trustsin 1a (AF217917) and VAMP2 (Vesicle-associated) from E. coli Codon (+) RIL, Novagen transformed by biological techniques to produce SNARE proteins, respectively. membrane protein 2: NM012663) was purified. First, palmitoyl oleoyl phosphatidylcholine (POP) (62 mol%), dioleoyl phosphatidylserine (DOPS) (35 mol%) 1-oleoyl-2- [N- (7-nitro-2,1,3-benzoxadiazol-4-yl) amino] caproyl phosphatidylserine (1-oleoyl-2- [N- (7-nitro -2,1,3-benzoxadiazol-4-yl) amino] caproylphosphatidylserine; NBD-PS] (1.5 mol%) and the phosphorescent rhodamine (Rhodamin-PE, 1.5 mol%) were mixed and 10 mM liposomes (v- vesicles, and 50 mM liposomes were prepared by mixing DOPS and POPC at a molar concentration of 35:65 to produce liposomes that were not labeled with a fluorescent substance. In order to make a molar concentration of 1: 1, the mixture was reacted for 1 hour at room temperature, and the fluorescent substance-labeled liposome and the molar ratio were 100: 1. VAMP2 was combined with a liposome containing a fluorescent material so that the molar ratio was 50: 1, and then the two liposomes were subjected to dialysis while stirring at 4 ° C. for 24 hours using a 10 kDa dialysis membrane. After mixing at a ratio of 3: 7 (v-vesicle: t-vesicle), the mixture containing SNAP-25, Trustsin 1a and VAMP-2 was added to the control methanol and Uiungreung extract at a concentration of 100 ppm and the fluorescence intensity Fluorescence intensity was measured using a measuring instrument (Model: SpectraMax M2, manufacturer: Molecular Device), and the results are shown in Table 1.

Since the fluorescence intensity in Table 1 means a membrane fusion phenomenon between SNARE proteins, a low fluorescence intensity indicates that membrane fusion was inhibited. As can be seen in Table 1, the Ureungchae extract treatment group was found to have an effect of inhibiting the membrane fusion between SNARE proteins because the fluorescence intensity is lower than the control group.

The fluorescence intensity of the control group was set as a reference, and the relative membrane fusion inhibition rate (%) in the Ureungchae extract treatment group was calculated. The results are shown in Table 1 below.

TABLE 1

Referring to Table 1, it can be confirmed that the membrane fusion inhibitory effect in the Ureungchae extract treatment group.

Experiment 2 Inhibitory Effect of Neurotransmitter Release on PC12 Cells

PC12 cells (Korean Cell Line Bank, Seoul, Korea) were cultured in Ham's F12K medium containing 10% calf serum, 5% fetal bovine serum and antibiotics in a collagen coated plate (60 mm dish). Subculture was inhaled medium, pipet into 2 ml of PBS and pipetted to separate the cells from the dish wall, centrifuged at 1,000xg for 5 minutes to collect the cells, and then pipette with fresh medium to disperse the cell pellet. Fresh culture plates were placed and incubated in an incubator at 37 ° C., 5% CO ₂ gas supplied.

[ ³ H] -noradrenaline used in the experiment was purchased from Amersham. After inhaling the medium from the plate of PC12 cells, PBS was added and the cells were detached from the plate wall, and the cells were measured by hematocytometer and dispersed in fresh medium at a concentration of 2 × 10 ⁵ cells / ml and inoculated. After 24 hours, noradrenaline assay buffer ([ ³ H] -NA, 1.5 μCi / ml) was added and then introduced in a carbon dioxide incubator for 90 minutes. After the reaction, the buffer solution was removed and washed three times with PBS. Then, Uirungchae extract (100 ppm), L-type calcium channel inhibitor verapamil (verapamil 10 μM), and botulinum toxin (2 nM) were added and reacted for 30 minutes. I was. After removal of the medium, a high concentration of K ⁺ buffer was added thereto, followed by incubation in a carbon dioxide gas incubator for 12 minutes, and the supernatant was recovered to determine whether it inhibited the release of [ ³ H] -noradrenaline by a scintillation counter. It was confirmed whether the Ureungchae extract extract group inhibited the release of noradrenaline in PC12 cells by the above method, and the results are shown in FIG. 1.

As can be seen in Figure 1, Ureungchae extract treatment group showed noradrenaline release inhibitory effect. In addition, since the inhibitory tendency of the substances on the secretion of noradrenaline and acetylcholine as a neurotransmitter in PC12 cells is similar, the inhibitory effect of noradrenaline release by Uiungreung extract can inhibit the release of acetylcholine neurotransmitter similar to botox. It may be.

Test Example 3 Pore Size and Sebum Analysis

Ten men and women who felt a lot of sebum secretion and facial pores were selected and prescribed according to Formula 2 of Table 6 below (using 0.5% of Ulleungchae extract) .The area with large sebum and large pores, mainly the skin around the cheeks and nose. Every evening, after 4 hours of face wash. Measurements were made by visual evaluation and instrument measurements before and after using the test product under constant temperature and humidity conditions. Visual evaluation was scored according to the degree felt by the person who participated in the test and shown in Table 2 below, skin pore size was measured using a pore size measuring device (Skin touch, in-house developed) and shown in Table 3 below. Sebum was measured using a sebum meter (sebumeter) and are shown in Table 4 below.

TABLE 2

[Table 3]

[Table 4]

From the results of Tables 2, 3 and 4, it was confirmed that the composition of the present invention has a pore size reduction and sebum inhibitory effect.

Examples of the formulation of the composition according to the present invention are described below, but are also applicable to various other formulations, which are intended to explain in detail only and not intended to limit the present invention.

Formulation Example 1 Flexible Cosmetics

According to the composition shown in Table 5 was prepared in the conventional method for the flexible cosmetic.

TABLE 5

Formulation Example 2 Nutritional Cosmetics

Nutritional longevity was prepared according to the composition described in Table 6 below in a conventional manner.

TABLE 6

Formulation Example 3 Nutrition Cream

Nutritional cream was prepared in a conventional manner according to the composition shown in Table 7.

TABLE 7

Formulation Example 4 Massage Cream

To prepare a massage cream in a conventional manner according to the composition shown in Table 8.

[Table 8]

[Formulation Example 5] Pack

To prepare a pack in a conventional manner according to the composition described in Table 9.

TABLE 9

Formulation Example 6 Ointment

The ointment was prepared in a conventional manner according to the composition described in Table 10 below.

TABLE 10

Formulation Example 7 Injection

Uireungchae Extract .................. 0.001-40 mg

Sterile Distilled Water for Injection ...

pH adjuster ...

According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).

Although the present invention has been described in connection with the above-mentioned embodiments, it is possible to make various modifications or variations without departing from the spirit and scope of the invention. Accordingly, the appended claims are intended to cover such modifications or changes as fall within the scope of the invention.

1 is a graph showing the measurement results of neurotransmitter release inhibitory effect in PC12 cells of Ureungchae extract in accordance with an embodiment of the present invention.

Claims (8)

A composition for inhibiting pore reduction or sebum secretion comprising the extract of Ulleungchae as an active ingredient. The method of claim 1, The composition inhibits the formation of a complex of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE), which inhibits pores shrinkage or sebum secretion that inhibits membrane fusion between synaptic vesicles and presynaptic membranes. Composition. The method of claim 2, The composition is a composition for inhibiting pore reduction or sebum secretion inhibiting the release of acetylcholine contained in the synaptic vesicles of the nerve terminal. The method of claim 1, The composition is a composition for inhibiting pore reduction or sebum secretion inhibiting the discharge of catecholamine-based neurotransmitters. The method of claim 1, The Ureungchae extract is a composition for inhibiting pore reduction or sebum secretion, characterized in that at least one solvent extract or fraction selected from the group consisting of water, ethanol and anhydrous methanol of Potentilla chinensis. The method of claim 1, The active ingredient is pore shrinkage or sebum secretion inhibiting composition is contained in an amount of 0.0001 to 30% by weight based on the total weight of the composition. A pharmaceutical composition comprising the composition according to claim 1. Cosmetic composition comprising a composition according to any one of claims 1 to 6.

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