KR101567571B1 - Cosmetic composition for body slimming containing 2-cyclopentene-1-one oxime derivatives - Google Patents

Abstract

A slimming cosmetic composition comprising a 2-cyclopenten-1-one oxime derivative represented by the formula (1) is disclosed. Specifically, the compound promotes lipolysis in differentiated adipocytes (3T3-L1) and consequently reduces the body fat, so that it can be used for cosmetic purposes such as slimming. In formula 1 R ₁ means a linear or branched C ₁ -C ₆ alkyl group, or a cycloalkyl group, or may have a substituent, or a phenyl group having no meaning does and, R ₂ is an aromatic group with or without substituents.

Description

TECHNICAL FIELD The present invention relates to a slimming cosmetic composition containing 2-cyclopenten-1-one oxime derivatives as an active ingredient,

The present invention relates to a slimming cosmetic composition comprising a 2-cyclopenten-1-one oxime derivative as an active ingredient.

Fat cells are the main fat stores in the body. They are not only storage containers for extra calories, they also have various functions such as cushioning function for protecting organs and maintaining body temperature.

White adipose tissue (WAT), which is mainly responsible for this role, synthesizes and stores excess nutrients in the form of triglycerides through LPL (lipoprotein lipase) in the blood vessel wall, Hormone sensitive lipase (HSL) is used to break down stored fat and supply it to each organ that needs energy.

During decomposition of these adipocytes, cyclic AMP (hereinafter referred to as cAMP) acts as a main factor mediating lipolysis. However, cAMP is very unstable and is converted to AMP by the phosphodiesterase present in cells, resulting in a decrease in cAMP concentration leading to degradation of lipolysis. Therefore, the mechanisms involved in the increase of cAMP levels in adipocytes and the various mechanisms involved in the inhibition of phosphodiesterase activity may play a role in promoting lipolysis.

Lipid degradation accelerators currently used mainly for cosmetic purposes include isoproterenol, a derivative of catecholamine, xanthine such as caffeine or theophylline, thyroid hormone, , Glucocorticoids, growth hormone (GH). However, these substances are either hormones or hormone derivatives, and their use is limited due to their side effects.

Accordingly, the present invention has been made to develop a lipid-degradation promoting agent that is effective for fat degradation and can be safely used. The present invention focuses on increasing the size of fat cells and fat storage which are becoming a cause of obesity, And to promote obesity by promoting exercise. Therefore, we are looking for a compound that can increase the cAMP concentration in adipocytes, and as a result, promote lipolysis to effectively effect lipolysis.

Thus, the present inventors have found that 2-cyclopenten-1-one oxime derivatives promote triglyceride degradation through increased cAMP concentration in adipocytes and have an effect on fat loss. Accordingly, the present invention provides a slimming cosmetic composition comprising a 2-cyclopenten-1-one oxime derivative as an active ingredient.

The cosmetic composition containing the 2-cyclopenten-1-one oxime derivative of the present invention as an active ingredient has a high level of cAMP by affecting intracellular cAMP production and degradation in fully differentiated adipocytes, , It can be usefully used in cosmetic compositions applied to local obesity or systemic obesity.

FIG. 1 is a graph comparing the rate of fat decomposition promotion and the rate of cAMP increase in adipocytes of 2-cyclopenten-1-one oxime derivative compounds according to an embodiment of the present invention.

Best Mode for Carrying Out the Invention

The present invention provides a slimming cosmetic composition comprising a 2-cyclopenten-1-one oxime derivative as an active ingredient. Here, "slimming" means that the body weight is decreased or the subcutaneous fat is locally decomposed, thereby reducing the size of the fat cells and decreasing the excessively accumulated fat, thereby changing the body shape.

The slimming cosmetic composition according to one embodiment of the present invention comprises a compound of the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

In this formula,

R ₁ means a linear or branched C ₁ -C ₁₀ alkyl group or a C ₃ -C ₇ cycloalkyl group or a phenyl group having or without a substituent and R ₂ means an aromatic group with or without a substituent, Means an aromatic group selected from gigaphenyl, pyridyl, naphthyl, indolyl, thienyl, benzo [b] thienyl, dibenzofuranyl or thianthrenyl.

The phenyl group is represented by the following general formula (2)

Wherein R ₃ to R ₇ are each independently selected from the group consisting of hydrido, linear or branched C ₁ -C ₉ alkyl, C ₂ -C ₆ alkenyl, haloC ₁ -C ₆ alkyl, phenyl, halo, nitro, Amino, C ₁ -C ₅ alkylamino, C ₁ -C ₅ alkylamino C ₁ -C ₅ alkyl, methylenedioxy, C ₁ -C ₅ alkoxy, C ₁ -C ₅ haloalkoxy, benzyloxy, C ₁ -C ₅ alkylthio, C ₁ -C ₅ alkylsulfonyl, C ₁ -C ₅ alkylsulfinyl, cyano, carboxy, C ₁ -C ₅ alkoxycarbonyl, C ₁ -C ₅ alkoxy C ₁ -C ₅ alkyl, hydroxy C ₁ -C ₅ alkyl, C ₁ -C ₅ carbamoyl, N-hydroxy-imino C ₁ -C ₅ alkyl or N- (N-hydroxy-imino C ₁ -C ₅ alkyl) Amino. ≪ / RTI >

In one preferred embodiment of the present invention, R ₁ in formula (1) represents linear or branched C ₁ -C ₆ alkyl, cyclopentyl or cyclohexyl, R ₂ represents an aromatic group with or without substituents, Wherein the aromatic group means an aromatic group selected from pyridyl, naphthyl, indolyl, thienyl, benzo [b] thienyl, dibenzofuranyl or thianthrenyl, or a phenyl group having a substituent. The phenyl group is as shown in the above formula (2).

In another preferred embodiment of the present invention, R ₁ in the formula (1) means a group having a substituent, and R ₁ means a group of a propyl group, an isopropyl group, a butyl group, an isobutyl group, a pentyl group, a cyclopentyl group or a cyclohexyl group. R ₃ to R ₇ are each independently selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, vinyl, trifluoromethyl, phenyl, fluoro, chloro, bromo N, N-dimethylamino, N, N-dimethylaminomethyl, methylenedioxy, methoxy, ethoxy, trifluoromethoxy, benzyloxy, methylthio, methylsulfonyl, methylsulfinyl, (Hydroxyacetamidoyl) amino, N-hydroxyiminomethyl, and 1-N-hydroxynaphthyl, each of which is optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, carboxy, methoxycarbonyl, ethoxycarbonyl, methoxymethyl, hydroxy, hydroxymethylcarbamoyl, Lt; RTI ID = 0.0 > Roximinoethyl. ≪ / RTI >

As another preferred embodiment of the present invention, at least one of the compounds disclosed in the following Table 1 or a pharmaceutically acceptable salt thereof may be contained as an active ingredient of the slimming cosmetic composition.

[Table 1]

The compound as described above or a pharmaceutically acceptable salt thereof may be contained in an amount of, for example, about 0.01 to 20% by weight, based on the total weight of the slimming cosmetic composition according to an embodiment of the present invention.

The slimming cosmetic composition according to one embodiment of the present invention can locally reduce the fat of these areas by directly applying to subcutaneous fat areas such as the face, abdomen, thighs, buttocks, upper arms, and the like. May be formulated in the form of a skin external preparation suitable for the purpose, and the formulation is not particularly limited.

That is, the slimming cosmetic composition according to one embodiment of the present invention may have a form applied to the skin such as an emulsion, a lotion, a gel, a cream, an oil, a spray, an ointment, a powder, a compact, a pack, For example, a cleanser, a shampoo, a rinse, or the like, and may have a form attached to the skin, for example, a patch, a pad, or the like.

Depending on the purpose of formulation or use of such cosmetics, the slimming cosmetic composition according to one embodiment of the present invention may be compounded with other components in addition to the above-mentioned compounds. For example, suitable carriers, excipients and diluents. Examples of suitable carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

DETAILED DESCRIPTION OF THE INVENTION

Hereinafter, the present invention will be described concretely with reference to Examples, but the present invention is not limited by the following Examples.

Example 1 Evaluation of Neutral Lipolysis Effect in Fat Cells

(Step 1) Culture and differentiation of fat cell lines

Mouse-derived preadipocytes in 3T3-L1 cells (adipocytes of mice; ATCC # CL-173) the 96-well cell to ensure that the 5x10 ⁴ / well in a culture plate with 10% bovine serum (Calf serum, GibcoBRL, # 16170 -078), and penicillin / streptomycin (GibcoBRL # 10378-016) a DMEM medium containing antibiotics (Dulbecco's modifided Eagle's medium, hereinafter referred to as DMEM, GibcoBRL, 11965-084 #) on, 37 ℃, 10% CO ₂ cell incubator And cultured. The following day, the cells were incubated with 10% fetal bovine serum, 0.5 mM 3-isobutyl-1-methyl xanthine (IBMX; Sigma # I- 7018), 1 μM dexamethasone (Sigma # D- After incubation for 48 hours in a medium containing 167 nM insulin (Sigma I-5500), the medium was replaced with insulin DMEM medium containing 10% bovine serum and 167 nM insulin, and cultured again for 72 hours Respectively. Subsequently, completely differentiated adipocytes were obtained by further culturing in DMEM medium containing only 10% fetal bovine serum (FBS; GibcoBRL 10437-028) for 48 hours.

(Step 2) Evaluation of the concentration of free glycerol (Glycerol)

The culture medium of fully differentiated 3T3-L1 cells was discarded and washed with PBS (-). Then, DMEM (Low glucose, without phenolred; WelGene # LM001-04) containing 2% BSA (Bovogen # ) 200ul / well so that the compounds 1 to 24 were respectively treated with 10 uM and final 0.5% DMSO, followed by culturing for 5 hours. Then, only the cell culture supernatant was taken and the amount of glycerol produced as a fat degradation product was measured using Free Glycerol Reagent (Sigma # F6428). At this time, the glycerol content was calculated by the method shown in the following formula 1, and the relative value for the case where the value of the control group (well without the compound, 0.5% DMSO) was taken as 100% Respectively.

Glycerol content = (A _sample - A _blank ) / (A _standard - A _blank ) X Glycerol Standard concentration

* A _sample : The absorbance of a well sample treated with each of the above compounds

* A _blank : Absorbance of the well sample not treated with indicator

* A _standard : Glycerol standard absorbance at the predetermined concentration externally indicated

(%) = (Amount of free glycerol at the time of adding the compound / amount of free glycerol at the time of no addition of the compound (0.5% DMSO control)) X 100

The results are shown in Table 2 below. It can be confirmed that all of the adipocyte promotion rate of the control group is superior to that of the adipocyte promotion rate of the control group.

[Table 2]

Example 2: Measurement of cAMP concentration in differentiated adipocytes

The concentration of cAMP induced by forskolin, an adenylate cyclase (AC) promoter, in the adipocytes differentiated as in step 1 of Example 1 was measured using a 2-cyclopenten-1-one oxime derivative compound To evaluate the effect of these factors. The final concentrations of the compounds 3 to 9 and the compounds 11, 14 and 17 were adjusted to 10 uM and 0.5%, respectively, after discarding the upper layer culture solution of the fully differentiated adipocytes and inserting the DMEM medium containing 10% fetal bovine serum (FBS) DMSO for 15 min in a 10% CO ₂ cell incubator at 37 ° C and stimulated with 1 uM forskolin at 37 ° C for 10 min. Thereafter, the cell culture medium was discarded and the cells were lysed. Then, the amount of intracellular cAMP was measured using a cAMP enzyme immunoassay (EIA) system (Amersham Pharmacia Biotech, Kit # RPN225). From the dose response curves of standard cAMP quantities, the effect on cAMP production or degradation of Compounds 3 to 9 and Compounds 11, 14, and 17 was evaluated. The stimulated samples were treated with 1 uM forskolin alone without each compound in 100 %, And the relative value of the compound-treated sample was determined. The results are shown in Table 3 below. These compounds induce high levels of cAMP in differentiated adipocytes by affecting intracellular cAMP production and degradation inhibition, which is thought to inhibit fat storage by stimulating HSL promoting lipolysis.

[Table 3]

Fig. 1 shows the comparison between the lipolysis promotion rate in Table 2 and the increase rate in cAMP cells in Table 3.

As can be seen from Tables 2 and 3 and FIG. 1, when the slimming cosmetic composition according to one embodiment of the present invention is treated on fully differentiated adipocytes (Differentiated 3T3-L1), lipid degradation, It was confirmed that the neutral lipid degradation was actively induced, which is attributable to the increase in cAMP concentration in adipocytes.

Accordingly, the slimming cosmetic composition according to one embodiment of the present invention can partially or wholly reduce the fat decomposition accumulated in subcutaneous fat or the like in a specific site, thereby reducing the whole body or local fat, It is very effective for

Formulation examples of the above composition will be described below, but the present invention is not to be construed as limiting, but rather is to be specifically described.

≪ Formulation Example 1: Milk solution >

The slimming cosmetic composition according to one embodiment of the present invention was formulated into an emulsion having the composition shown in Table 4 below.

[Table 4]

Formulation Example 2: Cream >

The cosmetic composition according to one embodiment of the present invention was formulated into cream with the composition shown in Table 5 below.

[Table 5]

≪ Formulation Example 3: Pack >

The cosmetic composition according to one embodiment of the present invention was formulated into a pack in the composition shown in Table 6 below.

[Table 6]

Claims (4)

A slimming cosmetic composition comprising a compound of the formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[Chemical Formula 1]

(Wherein,
R ₁ is a linear or branched C ₁ -C ₁₀ alkyl group or a C ₃ -C ₇ cycloalkyl group, or a phenyl group represented by the following formula (2)
R ₂ is an aromatic group selected from pyridyl, naphthyl, indolyl, thienyl, benzo [b] thienyl, dibenzofuranyl or thianthrenyl, or a phenyl group represented by the following formula (2)
(2)

Wherein R ₃ to R ₇ are each independently selected from the group consisting of hydrido, linear or branched C ₁ -C ₉ alkyl, C ₂ -C ₆ alkenyl, halo C ₁ -C ₆ alkyl, phenyl, halo, nitro, amino , C ₁ -C ₅ alkylamino, C ₁ -C ₅ alkylamino C ₁ -C ₅ alkyl, methylenedioxy, C ₁ -C ₅ alkoxy, C ₁ -C ₅ haloalkoxy, benzyloxy, C ₁ -C ₅ C ₁ -C ₅ alkylthio, C ₁ -C ₅ alkylsulfonyl, C ₁ -C ₅ alkylsulfinyl, cyano, carboxy, C ₁ -C ₅ alkoxycarbonyl, C ₁ -C ₅ alkoxy C ₁ -C ₅ alkyl, C ₁ -C ₅ alkyl, C ₁ -C ₅ carbamoyl, N-hydroxy-imino C ₁ -C ₅ alkyl or N- (N-hydroxy-imino C ₁ -C ₅ alkyl) amino . ≪ / RTI > The method according to claim 1,
Wherein R ₃ to R ₇ are each independently selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, vinyl, trifluoromethyl, phenyl, fluoro, chloro, bromo, nitro, Wherein the alkyl moiety is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, dimethylamino, N, N-dimethylaminomethyl, methylenedioxy, methoxy, ethoxy, trifluoromethoxy, benzyloxy, methylthio, methylsulfonyl, methylsulfinyl, Wherein the amino group is selected from the group consisting of methoxycarbonyl, ethoxycarbonyl, methoxymethyl, hydroxy, hydroxymethylcarbamoyl, N- (hydroxyacetimidoyl) amino, N-hydroxyiminomethyl or 1-N-hydroxyiminoethyl. The cosmetic composition according to claim 1, wherein the cosmetic composition accelerates the decomposition of fat to cause a decrease in triglyceride. The cosmetic composition according to claim 1, wherein the cosmetic composition is a single formulation selected from the group consisting of lotions, lotions, creams, gels, oils, sprays, ointments, powders, compacts, packs, cleansers, shampoos, rinses, patches and pads Cosmetic composition.

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