JP2011063527A - Carnitine production promoter and external preparation for skin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an external preparation for the skin capable of preventing liver spot, wrinkle, reduction of elasticity and drying of the skin by discovering an active ingredient having activities for promoting carnitine production in a living body, by promoting energy metabolism of the skin, and by ameliorating a barrier function by making the turning over of the skin healthy. <P>SOLUTION: The carnitine production promoter contains an extract of cherry as an active ingredient. The external preparation for the skin contains the extract of the cherry and/or the extract of fucus, and the carnitines. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a carnitine production promoter and a skin external preparation containing the same.

  One of the important roles of the skin is to protect the body as a barrier to external stimuli such as harmful substances, regulate water in the body, and maintain homeostasis in the living body. This role is mainly played by the stratum corneum, the outermost layer of the epidermis. However, if the skin environment is repeatedly disturbed by external factors such as dryness, ultraviolet rays, chemical substances, and internal factors such as oxidative stress and aging, the epidermis itself becomes thinner and the barrier function against external stimuli is reduced. However, phenomena such as exfoliation of keratinocytes due to drying of the skin surface, appearance of wrinkles, talmi and stains, tension and loss of elasticity, which are general signs of skin aging, appear. Also, if most of the epidermal function as a barrier is lost, it becomes difficult to maintain life itself. Therefore, maintaining or improving epidermal function is an important issue in preventing skin aging.

  Epidermal cells, which play the most important role in forming epidermal function, divide and proliferate in the innermost basal layer of the epidermis, change shape with spinous cells and granule cells, synthesize and secrete proteins and lipids The cells are repeatedly differentiated to form horny cells and form the outermost stratum corneum, and then turn into plaque and fall off. Therefore, proliferation of epidermal cells in the basal layer is important for strengthening epidermal function, and there are various blood circulation promoters and cell activators that directly activate epidermal cells for the purpose of supplying nutrition to basal layer cells. It is used.

  On the other hand, an energy source is necessary for the cells to be active, and a large amount of energy is required in the process of turning over epidermal cells with dramatic changes. It is known that sugar is the main energy source in the epidermis near the basal layer, whereas sugar is depleted near the stratum corneum, and fatty acids are the main energy source instead. (Non-Patent Document 1). Since energy metabolism from fatty acids is effected by β-oxidation, it is considered important to promote β-oxidation of epidermal cells in order to form a healthy epidermal function and prevent skin aging.

  The field of β-oxidation reaction is in mitochondria, but the fatty acid as a substrate cannot move alone into mitochondria. Carnitine is responsible for transporting this fatty acid, and is known to be a rate-limiting substance for β-oxidation reaction. Since the amount of carnitine in a living body decreases with aging (Non-patent Document 2), skin anti-aging agents containing carnitines as active ingredients have been reported (Patent Document 1).

  Carnitine has been said to be biosynthesized only in three organs: the liver, kidney, and brain, in addition to being ingested from food, but the inventors have confirmed the expression of synthase in epidermal cells as well as the above organs, It was reported that carnitine was actually synthesized (Non-patent Document 3).

JP 2001-240538 A

Dermatology, 20, 265-269, 1978 Biochem. Biophys. Res. Com. 161, 1135-143, 1989 Fragrance Journal, 33 (8), 81-83, 2005

  Under such circumstances, an object of the present invention is to find an active ingredient having an action of promoting carnitine production in the living body, promote energy metabolism of the epidermis, improve turnover and improve barrier function, and thereby improve skin function. An object of the present invention is to provide an external preparation for skin that can prevent spots, wrinkles, reduced elasticity and drying.

  As a result of searching for natural products that increase the amount of carnitine contained in epidermal cells, the present inventors have found that an extract obtained from a specific plant has carnitine production-promoting activity, leading to the completion of the present invention. It was.

  That is, the present invention provides a carnitine production promoter containing a cherry extract as an active ingredient. The present invention also provides a skin external preparation containing a cherry extract and / or a hibermata extract and carnitines.

  The cherry extract according to the present invention has an action of promoting carnitine production in epidermal cells. Further, the skin external preparation of the present invention containing a combination of a cherry extract and / or a Hibamata extract having a carnitine production promoting action in the same manner as the cherry extract and a carnitine has a carnitine production promoting effect from the inside. Due to the effect of supplying carnitines from the outside, it is possible to improve the activity of epidermal cells in the skin and prevent skin aging more effectively.

  Hereinafter, the configuration of the present invention will be described in detail. The cherry used in the present invention refers to a plant of the Rosaceae subgenus (Cerasus). Specific examples include Yoshino cherry, Oshima cherry, and bean cherry. Any part of the cherry may be used for extraction, and examples include whole grass, bark, leaves, flowers, and fruits.

  Hibamata used in the present invention refers to brown algae of the genus Fucusaeae (Fucus). For extraction, Hibamata whole plant is usually used, but a specific part may be used.

  Solvents for obtaining the extract include water, lower alcohols such as methanol, ethanol and isopropyl alcohol, polyhydric alcohols such as ethylene glycol, propylene glycol and 1,3-butylene glycol, ketones such as acetone, acetic acid Examples include esters such as ethyl, ethers such as diethyl ether, and aromatic hydrocarbon compounds such as benzene, and one or more of these are used in appropriate combination. Of these, it is preferable to use lower alcohol, water, or a mixture thereof.

  For extraction, low temperature extraction, room temperature extraction, or heat extraction is used, and the extraction time is not limited, but generally 30 minutes to 1 week is preferable. Also, the heating temperature is not limited, but generally 60 ° C to 90 ° C is preferable. The cherry or hibermata is generally subjected to extraction after cutting the dried one into an appropriate size. And generally 2-100 mass parts of said extraction solvents are used with respect to 1 mass part of dry matter conversion of the raw material with which it uses for extraction.

  For the extract, the extract may be filtered and the filtrate may be used as it is, but usually a concentrate obtained by concentrating the filtrate under normal pressure or reduced pressure or a solid obtained by evaporating the solvent to dryness is used. It is common to do. Moreover, in order to raise the density | concentration of the active ingredient in an extract, it is also possible to attach | subject to purification means, such as adsorption chromatography.

  In addition, as the extract of the cherry or hibermata of the present invention, a commercially available one can be used. For example, a cherry extract (manufactured by Ichimaru Falcos) is used as a cherry extract, and a homeo is used as a extract of hibermata. A shield (made by Atrium) is mentioned.

  As shown in Examples described later, the cherry extract has an effect of significantly promoting carnitine production in epidermal cells and is useful as a carnitine production promoter. Therefore, the carnitine production promoter containing the cherry extract promotes energy metabolism of the epidermis, improves the barrier function lowered by aging of the skin, and is used as a pharmaceutical, quasi-drug, and cosmetic product having an anti-aging effect. it can.

  The carnitine production promoter of the present invention contains a cherry extract as an active ingredient and can be used as preparations of various dosage forms such as oral preparations, intravenous injections, and external preparations.

  The external preparation for skin of the present invention contains a cherry extract and / or hibermata extract having carnitine production promoting action and carnitines. In the present invention, the external preparation for skin refers to all externally applied to the skin, regardless of pharmaceuticals, quasi-drugs, and cosmetics, and includes bathing agents. Although the form of the external preparation for skin according to the present invention is not particularly limited, for example, the form of general external preparation for skin such as aqueous solution, alcohol aqueous solution, emulsion, ointment, tablet, powder, cream, emulsion, lotion, etc. can do.

  The content of the cherry extract and hibamata extract in the carnitine production promoter or skin external preparation of the present invention is 0.00001 to 0.5 mass for the cherry extract in terms of solid content based on the total amount of the skin external preparation. % (Hereinafter referred to as "%"), preferably 0.001 to 5% for Hibamata extract, especially 0.0002 to 0.1% for Sakura extract, and 0.02 to 1% for Hibamata extract . Further, from the viewpoint of harmonizing with the color and odor of the external preparation for skin, it is preferable that the content of the cherry extract is 2% or less and the content of the hibermata extract is 5% or less.

  The skin external preparation of the present invention contains carnitines in addition to the cherry extract and / or hibamata extract. Combining the cherry extract and hibamata extract with carnitines promotes carnitine production from the inside in epidermal cells and at the same time supplies carnitines from the outside, further increasing energy metabolism in the epidermis. To be sound.

  The carnitines used in the present invention refer to carnitine, acylcarnitines, and salts thereof. Carnitine is 4-trimethylamino-3-hydroxybutyric acid (3-hydroxy-4-trimethylammoniobutanoic acid), and D-form and L-form exist as stereoisomers, and DL-form exists as a mixture of these. Are known. In the present invention, it is particularly preferable to use L-form or DL-form.

  Examples of the carnitine salt include hydrochloride, acetate, sulfate and the like, and carnitine chloride (carnitine hydrochloride) is particularly preferable. Examples of the acylcarnitine include acetylcarnitine described in JP-A-11-180851, specifically acetyl-L-carnitine. Examples of the salt of acylcarnitine include the same salts as the aforementioned carnitine salt, and hydrochloride is particularly preferable.

  The content of carnitine in the external preparation for skin of the present invention is preferably 0.01 to 5%, particularly preferably 0.1 to 2%, based on the total amount of the external preparation for skin.

  In the external preparation for skin of the present invention, various external preparation components that are usually used in external preparations for skin such as pharmaceuticals, quasi drugs and cosmetics can be appropriately blended in addition to the above essential components. Examples of such external preparation components include anionic surfactants, amphoteric surfactants, nonionic surfactants, thickeners, oil agents, powders (dyes, resins, pigments), preservatives, perfumes, and moisturizers. Agents, other physiologically active ingredients, salts, solvents, antioxidants, chelating agents, neutralizing agents, pH adjusting agents and the like.

  Hereinafter, the present invention will be described in more detail with reference to production examples, test examples, and formulation examples.

Production Example 1 (Manufacture of cherry extract)
A 50% ethanol extract of cherry was prepared as follows. 100 g of dried Yoshino leaf was pulverized in a mill and extracted with 1000 mL of 50% ethanol for 1 week. The extract was passed through filter paper and further filtered through a membrane having a filtration pore size of 0.22 μm (Millipore). Finally, the filtered extract was freeze-dried to obtain a 50% ethanol extract powder of cherry.

Production Example 2 (Production of Hibamata extract)
Hibamata's hot water extract was produced as follows. 100 g of the dried product was pulverized with a mill, 1000 mL of water was added, and extraction was performed at 80 ° C. for 60 minutes. After cooling, the extract was passed through filter paper and further filtered through a membrane having a filtration pore size of 0.22 μm (manufactured by Millipore). The filtered extract was lyophilized to obtain a hot water extract powder of Hibamata.

Test example (evaluation of carnitine production promoting effect)
The cherry extract produced in Production Example 1 and the Hibamata extract produced in Production Example 2 were used as evaluation samples, and their carnitine production promoting effects were evaluated by the following procedure.

Normal human epidermal cells (Epidercell / newborn foreskin, manufactured by Kurabo Industries Co., Ltd.) are seeded at 1 × 10 ⁵ in a 6 cm dish, and hydrocortisone (0.5 μmol) is based on MCDB153HAA medium (amino acid enriched medium, manufactured by Wako Pure Chemical Industries, Ltd.). / L), ethanolamine (0.1 mmol / L), phosphoethanolamine (0.1 mmol / L), insulin (5 μg / mL), EGF (epidermal growth factor: 10 ng / mL), and BPE (beef bovine brain) Culture was performed in a medium supplemented with pituitary extract (manufactured by Kurabo Industries Co., Ltd .: 4 μL / mL). After culturing for 4 days, BPE was removed from the above medium and replaced with a medium to which the evaluation sample was added at a predetermined concentration, and cultured for 2 to 4 days. The final concentration (converted to the solid content) is 0, 0.0002, 0.0006, 0.002% by mass for the cherry extract, and the final concentration (converted to the solid content) is 0, 0.02, 0.02% for the Hibamata extract. It added so that it might become each concentration of 06 and 0.2 mass%. After culturing, the medium was removed and distilled water was added to recover the cells. After sonication, the cells were centrifuged, and the supernatant was ultrafiltered with a YM-3 column (Millipore). On the other hand, from the replica dish prepared at the time of cell seeding, cells were collected by adding PBS after culture, sonicated and centrifuged, and the amount of protein in the supernatant was measured using DC Protein Assay Kit (manufactured by Bio-Rad). Measured with

  Using the filtrate after ultrafiltration as a sample, LC-MS / MS analysis was performed under the following conditions, and the amount of carnitine in the filtrate was evaluated using the LC peak area per unit protein amount as an index. For LC, Agilent 1200LC-SL system was used, and for MS, Applied Biosystems 3200QTRAP system was used.

LC condition column: COSMOSIL HILIC (φ2.0 × 150cm, manufactured by Nacalai Tesque)
Column temperature: 30 ° C
Flow rate: 200 μL / min
Mobile phase: 100 mmol / L ammonium acetate solution (A) / acetonitrile (B)
Elution conditions: [A10%, B90%] → 14 minutes → [A80, B20%] (linear gradient)
MS condition scan type: MRM (Q1 Mass 162.1 Q3 Mass 85.1)
Ionization method: ESI

  The results are listed in Table 1. It is clear that the cherry extract and Hibamata extract promote their carnitine production in human normal epidermal cells. Therefore, by combining Sakura extract and / or Hibamata extract with carnitines in skin external preparations, it promotes energy metabolism of the epidermis that decreases with age, improves the barrier function of skin and prevents aging Expected to work.

  The skin external preparation of this invention is shown below as a formulation example. In addition, the numerical value in the compounding composition of each prescription example means the mass%.

Formulation Example 1 (Cream)
A cream having the following composition was prepared. Specifically, the hydrophilic component was heated to 80 ° C. in a hot water bath, and gradually added to the mixed lipophilic component with stirring. Furthermore, the mixture was sufficiently emulsified and dispersed by stirring with a homogenizer, and then gradually cooled with stirring to obtain a cream.
(Composition composition)

[Lipophilic component]
Squalane 4.7
White squalane 24.1
Stearyl alcohol 8.7
Isopropyl myristate 6.0
Isopropyl monostearate 1.3
Polyoxyethylene (12-16) 2.3
Alkyl ether phosphate Monoglyceryl monostearate 2.0
Paraoxybenzoic acid 0.1
L-carnitine chloride 1.0
Sakura extract (Production Example 1) 0.001
[Hydrophilic component]
Methyl paraoxybenzoate 0.1
Propylene glycol 6.7
Purified water balance

Formulation Example 2 (Lotion)
A lotion having the following composition was prepared according to a conventional method.
(Composition composition)

Ethanol 10.0
Lactic acid 0.3
Sodium citrate 0.1
Glycerin 2.0
Hibamata extract (Production Example 2) 0.1
L-carnitine 0.5
Preservatives, fragrances and surfactants Appropriate amount Purified water remaining

Formulation Example 3 (Bath Agent)
A bath preparation having the following composition was prepared according to a conventional method. In addition, this bath agent is diluted about 3000 times at the time of use.
(Composition composition)

Sodium sulfate 85.0
Perfume and surfactant Appropriate amount Organic dye Appropriate amount Sakura extract (Production Example 1) 0.1
Hibamata extract (Production Example 2) 1.0
L-carnitine chloride 3.0
Residual amount of sodium bicarbonate

Formulation Example 4 (Lotion)
A lotion having the following composition was prepared according to a conventional method.
(Composition composition)

Ethanol 10.0
Polyoxyethylene monolaurate 3.0
Sorbitan (20E.O.)
1,3-butylene glycol 4.0
Methylparaben 0.05
Phenoxyethanol 0.3
Sakura extract (Production Example 1) 0.01
Hibamata extract (Production Example 2) 0.01
L-carnitine chloride 2.0
N-lauroyl sarcosine isopropyl 0.1
Dutch mustard extract 0.1
Carrot extract 0.1
Honeysuckle extract 0.1
Niacinamide 0.1
Lactic acid bacteria whey 0.1
Purified water balance

Formulation Example 5 (Emulsion)
An emulsion having the following composition was prepared according to a conventional method.
(Composition composition)

Ethanol 10.0
Polyoxyethylene oleyl ether (2E.O.) 0.2
Polyoxyethylene cetyl ether (2E.O.) 0.1
Polyoxyethylene hydrogenated castor oil (60 EO) 0.3
Methylphenylpolysiloxane 1.0
Dimethylpolysiloxane 1.0
Glyceryl tri-2-ethylhexanoate 1.0
N-lauroyl sarcosine isopropyl 5.0
2-Ethylhexyl paramethoxycinnamate 1.0
Sakura extract (Production Example 1) 0.05
Hibamata extract (Production Example 2) 0.05
L-carnitine 1.0
Lauroyl-L-glutamate sodium 1.0
Dipropylene glycol 1.0
Concentrated glycerin 2.0
Carboxyvinyl polymer 0.3
Potassium hydroxide 0.15
Edetate disodium 0.01
Purified water balance

Formulation Example 6 (Emulsion)
An emulsion having the following composition was prepared according to a conventional method.
(Composition composition)

Ethanol 10.0
Soy phospholipid 1.0
Cholesterol 0.1
Sakura extract (Production Example 1) 0.01
Hibamata extract (Production Example 2) 0.01
L-carnitine 1.5
N-lauroyl sarcosine isopropyl 3.0
L-serine 2.0
Polyoxyethylene methyl glucoside 2.0
Polyglycerin 1.0
Liquid paraffin 1.0
Cyclopentapolysiloxane 1.0
Carboxyvinyl polymer 0.2
Triethanolamine 1.0
Xanthan gum 0.1
Methylparaben 0.1
Purified water balance

Formulation Example 7 (O / W type cream)
An O / W cream having the following composition was prepared according to a conventional method.
(Composition composition)

Cetanol 5.0
Lipophilic glyceryl monostearate 1.0
Polyoxyethylene cetyl ether 0.1
Hibamata extract (Production Example 2) 0.05
L-carnitine chloride 0.5
N-lauroyl sarcosine isopropyl 5.0
Butylparaben 0.1
Methylphenylpolysiloxane 2.0
Squalane 2.0
Sucrose fatty acid ester 0.5
Methylparaben 0.1
Sodium L-hyaluronate 0.1
Acrylic acid / alkyl methacrylate copolymer 0.1
Sodium hydroxide 0.05
Methylparaben 0.1
Purified water balance

Formulation Example 8 (W / O type cream)
A W / O type cream having the following composition was prepared according to a conventional method.
(Composition composition)

Sorbitan monoisostearate 1.0
Sakura extract (Production Example 1) 0.01
L-carnitine chloride 1.0
2,2′-dihydroxy-5,5′-1.0
Di-n-propylbiphenyl N-lauroyl sarcosine isopropyl 5.0
Poly (oxyethylene oxypropylene) 1.0
Methylpolysiloxane copolymer Cyclopentapolysiloxane 8.0
Sodium chloride 1.0
Magnesium chloride 1.0
Dipropylene glycol 7.0
Methylparaben 0.1
Fine particle titanium oxide 2.0
Purified water balance

Formulation Example 9 (Sunscreen)
A sunscreen having the following composition was prepared according to a conventional method.
(Composition composition)

Methylphenylpolysiloxane 1.0
Glyceryl tri-2-ethylhexanoate 2.0
2-Ethylhexyl paramethoxycinnamate 3.0
4-tert-butyl-1.0
4′-methoxybenzoylmethane dimethoxybenzylidenedioxoimidazolidine 1.0
2-ethylhexyl propionate cherry extract (Production Example 1) 0.01
Hibamata extract (Production Example 2) 0.01
L-carnitine chloride 2.0
Phenylbenzimidazole 3.0
Sodium sulfonate lipophilic glyceryl monostearate 1.0
Polyoxyethylene oleyl ether 0.3
Sodium phosphate (2E.O.)
Butylparaben 0.1
Stearoyl-potassium L-glutamate 0.3
Fine particle titanium oxide 3.0
Fine zinc oxide 7.0
Methylparaben 0.1
Purified water balance

Formulation Example 10 (Lotion)
A lotion having the following composition was prepared according to a conventional method.
(Composition composition)

Ethanol 10.0
Polyoxyethylene hydrogenated castor oil (60 EO) 1.0
Glycerin 3.0
1,3-butylene glycol 2.0
Dipropylene glycol 3.0
Polyethylene glycol 1500 1.0
Potassium dihydrogen phosphate 0.07
Potassium monohydrogen phosphate 0.03
Methylparaben 0.1
Hibamata extract (Production Example 2) 0.1
L-carnitine chloride 1.5
Purified water balance

Formulation Example 11 (Emulsion)
An emulsion was prepared by adding Component B having the following composition to Component A and stirring.
(Composition composition)

[Component A]
Stearic acid 1.0
Stearic acid glycerin ester 2.0
Cetanol 1.0
Cholesterol 0.5
Vaseline 2.0
Squalene 5.0
Liquid paraffin 5.0
Dimethylpolysiloxane (* 1) 1.0
Butylparaben 0.1
[B component]
Sakura extract (Production Example 1) 0.02
Hibamata extract (Production Example 2) 0.02
L-carnitine chloride 2.0
Acyl glutamate 1.0
Alkyl-modified carboxyvinyl polymer (* 2) 0.2
Glycerin 2.0
Dipropylene glycol 3.0
Purified water balance

* 1: Silicon KF-96 (100cs, manufactured by Shin-Etsu Chemical Co., Ltd.)
* 2: PEMULEN TR-1 (BF. Goodrich)

  As described above, the present invention can provide a carnitine production promoter that works on epidermal cells to promote carnitine production. In addition, by applying the carnitine production promoter of the present invention to a carnitine in combination with an external preparation for skin, the energy metabolism that decreases due to aging, etc. is improved, and the skin barrier function improving action and anti-aging action are achieved. Various skin external preparations can be provided.

Claims (2)

  Carnitine production promoter containing cherry extract as an active ingredient.   A skin external preparation containing a cherry extract and / or a Hibamata extract and carnitines.