JP2006001837A - Opioid receptor damage inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain an opioid receptor damage inhibitor especially having effective preventing and ameliorating effects on skin dysfunction caused by damage to the opioid receptor in relation to the opioid receptor damage inhibitor. <P>SOLUTION: The opioid receptor damage inhibitor effective for preventing the damage to the opioid receptor due to external irritation is obtained by containing an extract from a mushroom belonging to the genus Ganoderma. A cosmetic, a quasi-drug and a medicine comprise the opioid receptor damage inhibitor. The opioid receptor damage inhibitor and a skin care preparation for external use comprising the opioid receptor damage inhibitor have inhibitory actions on the damage to the opioid receptor promoted through the external irritation such as ultraviolet light. For further detail, the opioid receptor damage inhibitor is effective for ameliorating skin barrier dysfunctions induced by the damage to the opioid receptor and preventing drying of skin, ameliorating the skin roughening and ameliorating dullness, or the like, caused by keratin hyperplasia. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to an opioid receptor injury inhibitor, and in particular, an object of the present invention is to provide an opioid receptor injury inhibitor that has an effective prevention and improvement effect against a decrease in skin function caused by opioid receptor injury. Specifically, by containing an extract of a mushroom belonging to the genus Amanita, it has an excellent inhibitory effect on opioid receptor damage of skin cells promoted by external stimuli such as ultraviolet rays and inflammation, and damage of opioid receptor It is related with the opioid receptor injury inhibitor with which the improvement effect of the skin barrier function induced | guided | derived by the reduction | decrease, skin dryness, rough skin, dullness accompanying keratinous thickening etc. is anticipated.

The opioid receptor is a receptor that specifically binds to an endogenous opioid peptide typified by β-endorphin and exhibits morphine-like analgesic action. Conventionally, it has been considered to be distributed in pain transmission pathways such as nerve cells, but recently it has been confirmed that it is widely distributed in the living body, and a wide range of functions of endogenous opioid peptides has been suggested (Non-patent Document 1). Also in the skin, expression of opioid receptors and secretion of opioid peptides have been confirmed in epidermal keratinocytes and fibroblasts, which are the main cells constituting the skin, and research on their functions is ongoing.
Kazutomo Imabori, Biochemistry Dictionary, 3rd edition, Tokyo Chemical Doujin, 255-254, 1998.

As an effect of the opioid receptor on skin cells, it is reported that the production of Cytokeratin 16 (cytokeratin 16), which is a differentiation marker of epidermal keratinocytes, is increased by binding to β-endorphin, which is an agonist (Non-patent Document 2). There is also a report (Non-patent Document 3) that migration of keratinocytes is stimulated. In other words, the opioid receptor is considered to have an important action of promoting epidermal differentiation via β-endorphin. Therefore, by suppressing or repairing opioid receptor disorders, the skin barrier function has been normalized, and it has become possible to particularly effectively improve the prevention of skin dryness, improvement of rough skin, dullness due to keratin thickening, etc. .
Bigiardi-Qi M. , J .; Invest. Dermatol. 114: 527-532, 2000. Bigialdi PL, J.M. Receptors Signal Transduction, 22: 191-199, 2002.

  In addition, the skin is constantly subjected to stimuli such as ultraviolet rays, heat, physical stimulation, and inflammation. These external stimuli may damage opioid receptors and reduce the action of β-endorphin on skin cells. In other words, despite the presence of β-endorphin, the damage to the opioid receptor, which is the receptor, does not sufficiently exhibit the action of β-endorphin on skin cells, resulting in decreased skin function such as reduced epidermal differentiation. It is likely that this will happen.

  An object of the present invention is to provide an opioid receptor injury inhibitor that suppresses opioid receptor injury of skin cells due to external stimulation and has an effective prevention and improvement effect on the resulting decrease in skin function.

  Under these circumstances, as a result of intensive research, the present inventors have found that an extract of a mushroom belonging to the genus Mannenmus has an excellent inhibitory effect on opioid receptor injury of skin cells. It came to complete.

  The extract of the mushroom belonging to the genus Amanita of the present invention and the opioid receptor injury inhibitor containing the same have an inhibitory effect on opioid receptor damage of skin cells promoted by external stimulation. More specifically, the present invention relates to an opioid receptor injury inhibitor effective in improving the decrease in skin barrier function induced by opioid receptor damage, and effective in preventing skin dryness, improving rough skin, and dullness associated with keratin thickening.

  The garlic mushrooms used in the present invention belong to the genus Mushroom family and the genus Mungella mushroom, and are reishi (red ganoderma, scientific name: Ganoderma lucidum), black ganoderma (scientific name: G. japonicum, G. sinense, G. atrum), purple ganoderma. (Scientific name: G. japonicum, G. sincense), sagebrush (scientific name: G. neo-japonicum), and the like. Examples of the extract of the garlic mushroom of the present invention include extracts such as fruit bodies and mycelia, and these may be used alone or in combination. Moreover, you may use the extract of a nanentake together.

  Among the mushrooms belonging to the genus Bamboo genus as described above, banyan mushroom and maggot are preferred.

  Moreover, the extract of the mushroom which belongs to the genus Mushroom used in the present invention is obtained by immersing or heating the mushroom belonging to the genus Mushroom with an extraction solvent, followed by filtration and, if necessary, concentration. Examples of the extraction solvent include water, lower monohydric alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), liquid polyhydric alcohols (1,3-butylene glycol, propylene). Glycol, etc.), hydrocarbons (hexane, pentane, etc.), ketones (acetone, methyl ethyl ketone, etc.), ethers (ethyl ether, tetrahydrofuran, propyl ether, etc.), acetonitrile and the like. These solvents may be used alone or in combination of two or more. Preferably, one or two or more of water or a water-soluble solvent (solvent that can be mixed with water in an arbitrary ratio. For example, ethanol, 1,3-butylene glycol, propylene glycol, etc.) may be used. . The extract may be used as it is, or a part or all of the solvent may be distilled off.

  As the opioid receptor injury suppressor of the present invention, the extract of the mushroom belonging to the genus Bamboo genus may be used as it is, and within the range where the effect is not impaired, the fats and oils and waxes that are components used in ordinary external preparations are used. , Hydrocarbons, fatty acids, alcohols, esters, surfactants, metal soaps, pH adjusters, preservatives, fragrances, moisturizers, powders, UV absorbers, thickeners, pigments, antioxidants Ingredients such as whitening agents and chelating agents can also be blended.

  The opioid receptor injury inhibitor used in the present invention can be used for cosmetics, quasi-drugs, and pharmaceuticals. Examples of the dosage form include skin lotion, cream, emulsion, gel, aerosol, pap Agents, essences, packs, cleaning agents, bath preparations, foundations, dusting powders, lipsticks, ointments, shampoos, rinses, treatments, tonics and the like.

  Although the compounding quantity of the extract of the mushroom which belongs to the genus Mushroom used for this invention is not specifically limited, The range of 0.0001 to 75 weight% is preferable as a dried material, More preferably, it is 0.001 to 30 weight%. If it is 0.0001% by weight or less, the effect is low, and even if it exceeds 75% by weight, the effect is hardly increased and it is not efficient. The addition method may be added in advance or during the production, and may be appropriately selected in consideration of workability.

  Next, in order to describe the present invention in detail, examples of production of the extract used in the present invention, formulation examples and experimental examples will be given as examples, but the present invention is not limited thereto. The compounding amount shown in the examples indicates% by weight.

Production Example 1 Hot water extract of pearl oyster 400 mL of purified water was added to 20 g of dried pearl oyster and extracted at 95-100 ° C. for 2 hours. The insoluble matter was filtered, the filtrate was concentrated, freeze-dried, and pearl jelly. 2.0 g of a hot water extract was obtained.

Production Example 2 Hot Water Extract of Black Ganoderma After adding 400 mL of purified water to 20 g of dried Kuro Ganoderma and extracting at 95-100 ° C. for 2 hours, the insoluble matter is filtered, and the filtrate is concentrated and frozen. Drying gave 1.3 g of hot water extract of black ganoderma.

Production Example 3 Ganoderma Hot Water Extract 400 g of purified water is added to 20 g of dried ganoderma and extracted at 95-100 ° C. for 2 hours, then insoluble matter is filtered, and the filtrate is concentrated and freeze-dried. 1.4 g of hot water extract of Ganoderma was obtained.

Manufacture example 4 Ethanol extract of pearl oyster 900 mL of ethanol was added to 100 g of dried magpie, and extracted at room temperature for 7 days. The insoluble matter was filtered, and the filtrate was concentrated to dryness to obtain 1.5 g of coconut extract. Got.

Production Example 5 Black Ganoderma Ethanol Extract 900 g ethanol was added to 100 g of dried black ganoderma turf, extracted for 7 days at room temperature, insoluble matter was filtered, and the filtrate was concentrated to dryness. 1.5 g of ethanol extract was obtained.

Production Example 6 Ganoderma Ethanol Extract 900 g of ethanol was added to 100 g of Ganoderma lucidum, extracted for 7 days at room temperature, insoluble matter was filtered, the filtrate was concentrated to dryness, and Ganoderma ethanol extract. 1.6 g was obtained.

Production Example 7 1,3-butylene glycol aqueous extract of maggots 1 kg of purified water and 1 kg of 1,3-butylene glycol were added to 100 g of dried maggots, extracted at room temperature for 7 days, insolubles were filtered, 1.9 kg of 1,3-butylene glycol aqueous extract of maggot was obtained.

Manufacture example 8 1,3-butylene glycol aqueous solution extract of black ganoderma 1 kg of purified water and 1 kg of 1,3-butylene glycol are added to 100 g of dried black ganoderma and extracted at room temperature for 7 days, and then insoluble. Was filtered to obtain 1.9 kg of a 1,3-butylene glycol aqueous extract of black ganoderma.

Production Example 9 Extract from Ganoderma 1,3-butylene glycol aqueous solution Add 1 kg of purified water and 1 kg of 1,3-butylene glycol to 100 g of dried ganoderma and extract for 7 days at room temperature, then filter insolubles As a result, 1.9 kg of 1,3-butylene glycol aqueous extract of Ganoderma was obtained.

  Next, the prescription of the Example which concerns on this invention is shown.

Formulation Example 1 Cream Formulation Amount (% by weight)
1. Hot water extract of maggots (Production Example 1) 0.05
2. Squalane 5.5
3. Olive oil 3.0
4). Stearic acid 2.0
5. Beeswax 2.0
6). Octyldodecyl myristate 3.5
7). Polyoxyethylene cetyl ether (20E.O.) 3.0
8). Behenyl alcohol 1.5
9. Glycerol monostearate2.5
10. Fragrance 0.1
11.1,3-butylene glycol 8.5
12 Ethyl paraoxybenzoate 0.05
13. Methyl paraoxybenzoate 0.2
14 Purified water 68.1
[Production Method] Components 2 to 9 are heated and mixed, and kept at 70 ° C. to obtain an oil phase. Ingredients 1 and 11 to 14 are dissolved by heating and mixed, and kept at 75 ° C. to form an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring. The component 10 is added at 45 ° C, and further cooled to 30 ° C to obtain a product.

Comparative Example 1 Conventional Cream In Example 1, a conventional cream was prepared by replacing the hot water extract of maggots with purified water.

Formulation Example 2 Lotion Formulation Amount (% by weight)
1. Black Ganoderma Hot Water Extract (Production Example 2) 0.01
2. 1,3-butylene glycol 8.0
3. Glycerin 2.0
4). Xanthan gum 0.02
5. Citric acid 0.01
6). Sodium citrate 0.1
7). Ethanol 5.0
8). Methyl paraoxybenzoate 0.1
9. Polyoxyethylene hydrogenated castor oil (40E.O.) 0.1
10. Fragrance 0.1
11. Purified water 84.56
[Production method] Components 1 to 6 and 11 and components 7 to 10 are uniformly dissolved, and both are mixed and filtered to obtain a product.

Formulation Example 3 Emulsion Formulation Amount (wt%)
1. Reishi hot water extract (Production Example 3) 0.05
2. Squalane 5.0
3. Olive oil 5.0
4). Jojoba oil 5.0
5. Cetanol 1.5
6). Glycerol monostearate 2.0
7). Polyoxyethylene cetyl ether (20E.O.) 3.0
8). Polyoxyethylene sorbitan monooleate 2.0
9. Fragrance 0.1
10. Propylene glycol 1.0
11. Glycerin 2.0
12 Methyl paraoxybenzoate 0.2
13. Purified water 73.15
[Manufacturing method] Components 2 to 8 are dissolved by heating and mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 1 and 10-13 are dissolved by heating and mixed, and kept at 75 ° C. to form an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring.

Formulation Example 4 Ointment Formulation Amount (% by weight)
1. Maggots ethanol extract (Production Example 4) 1.0
2. Polyoxyethylene cetyl ether (30E.O.) 2.0
3. Glycerol monostearate 10.0
4). Liquid paraffin 5.0
5. Cetanol 6.0
6). Methyl paraoxybenzoate 0.1
7). Propylene glycol 10.0
8). Purified water 65.9
[Manufacturing method] Components 2 to 5 are dissolved by heating and mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 1 and 6 to 8 are dissolved by heating and mixed, and kept at 75 ° C. to obtain an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled to 30 ° C. with stirring to obtain a product.

Formulation Example 5 Foundation Formulation Amount (% by weight)
1. Kuro Reishi ethanol extract (Production Example 5) 1.0
2. Stearic acid 2.4
3. Polyoxyethylene sorbitan monostearate 1.0
(20E.O.)
4). Polyoxyethylene cetyl ether (20E.O.) 2.0
5. Cetanol 1.0
6). Liquid lanolin 2.0
7). Liquid paraffin 3.0
8). Isopropyl myristate 6.5
9. Butyl paraoxybenzoate 0.1
10. Sodium carboxymethylcellulose 0.1
11. Bentonite 0.5
12 Propylene glycol 4.0
13. Triethanolamine 1.1
14 Methyl paraoxybenzoate 0.2
15. Titanium dioxide 8.0
16. Talc 4.0
17. Bengala 1.0
18. Yellow iron oxide 2.0
19. Fragrance 0.1
20. Purified water 60.0
[Manufacturing method] Components 2 to 9 are heated and dissolved and kept at 80 ° C to obtain an oil phase. Swell component 10 well with component 20, then add components 1 and 11-14 and mix uniformly. To this, components 15 to 18 pulverized and mixed with a pulverizer are added, and the mixture is stirred with a homomixer and kept at 75 ° C. to obtain an aqueous phase. The oily phase is added to the aqueous phase with stirring, cooled, and component 19 is added at 45 ° C, and cooled to 30 ° C with stirring to give a product.

Formulation Example 6 Bath formulation Formulation amount (% by weight)
1. Magella's 1,3-butylene glycol 5.0
Aqueous solution extract (Production Example 7)
2. Sodium bicarbonate 50.0
3. Yellow No. 202 (1) 0.05
4). Fragrance 0.25
5. Anhydrous sodium sulfate 44.7
[Production method] Components 1 to 5 are uniformly mixed to obtain a product.

  Next, experimental examples will be given to explain the effects of the present invention in detail.

Experimental Example 1 Opinoid Receptor Reduction Inhibition Test by Ultraviolet Light The opioid receptor reduction inhibitory effect was measured under the following conditions.

Confluent human epidermal keratinocytes were irradiated with 40 mJ / cm ² UVB. Next, after further culturing in DMEM medium supplemented with 10 μg / mL sample, total protein was extracted. 10 μg of this protein was subjected to SDS polyacrylamide gel electrophoresis and then blotted on a transfer membrane (Millipore). After completion of blotting, Mu Opioid Receptor Polyantibody (Neuromics) is used as the primary antibody, Anti-Rabbit IgG HRP-Linked antibody (Amersham) is used as the secondary antibody, and ECL Western blotting detection reagent (Amersham) is used as the detection reagent. Was detected as a band. These bands were quantified with a densitometer. A decrease in opioid receptor protein is seen in cells irradiated with UVB compared to cells not irradiated with UVB. From the decrease value (B) of the opioid receptor protein amount at the time of sample addition to the decrease value (A) of the opioid receptor protein amount of this control, the reduction inhibition rate of the opioid receptor was determined by the following formula.

Reduction rate of opioid receptor decrease (%) = (1−B / A) × 100

  The test results are shown in Table 1. As a result, an excellent opioid receptor decrease-suppressing effect was observed in the extract of mushrooms belonging to the genus Amanita.

Experimental Example 2 Use Test Using the cream of Prescription Example 1 and the conventional cream of Comparative Example 1, a use test was conducted for 30 months (20 to 45 years old) suffering from rough skin for 1 month. After use, a questionnaire survey on the improvement of rough skin, dry skin and transparency was conducted to determine the improvement effect of skin properties. The evaluation criteria of the questionnaire were evaluated as “excellent” for valid, “good” for slightly effective, “good” for slightly effective, and “impossible” for invalid.

  These results are shown in Table 2. The external preparation for skin containing the opioid receptor injury inhibitor of Formulation Example 1 showed an excellent effect of improving skin properties. During the test period, there was no skin problem and there was no problem with safety.

  When the usage tests of the lotions, emulsions, ointments, foundations and bath preparations of Formulation Examples 2 to 6 were performed, all of them showed a safe and excellent skin property improving effect.

As an application example of the present invention, it can be used for any of cosmetics, quasi drugs and pharmaceuticals. Examples of the dosage form include skin lotion, cream, milky lotion, and the like, and when applied externally, improvement effects such as prevention of rough skin, skin dryness and dullness resulting from a decrease in skin barrier function are expected.

Claims (5)

  An opioid receptor injury inhibitor comprising an extract of mushrooms belonging to the genus Mannentake.   An opioid receptor injury inhibitor whose mushrooms belonging to the genus Mannentake are maggots.   An agent for promoting differentiation of epidermal keratinocytes, comprising an extract of a mushroom belonging to the genus Mannentake.   A skin barrier function recovery promoter comprising an extract of a mushroom belonging to the genus Mannentake.   An external preparation for skin, comprising the opioid receptor injury inhibitor according to claim 1 or 2.