JP2001192315A - Dermal elasticity improving agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a dermal elasticity improving agent which exhibits a dermal elasticity improving effect and a skin straining effect, prevents or improves the change in the dermal state, e.g. dermal wrinkles caused by various causes, flabbiness, loss of tension and elasticity, somberness, stains, freckles or the like, effectively and is useful as a medicine or a cosmetic. SOLUTION: This dermal elasticity improving agent or skin straining agent is obtained by including a glyceryl ether derivative represented by the following general formula (I) wherein, R shows an 8-30C alkyl or alkenyl group; X1 and X2 show each H atom, -SO3M1 or -PO3M1M2 (here, M1 and M2 are each identical or different and show H atom, an alkali metal, an alkaline earth metal or an ammonia group; however, X1 and X2 are not simultaneously H atoms) as an active ingredient.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a skin elasticity improving agent and a skin tightening agent containing a glyceryl ether derivative as an active ingredient.

[0002]

2. Description of the Related Art The skin is constantly exposed to external stimuli such as dryness and ultraviolet rays, and loses its elasticity with age, causing wrinkles and sagging.
Its properties change, such as reduction of beam, pigmentation, and color change. However, at present, studies on these morphological changes of skin have not been sufficiently advanced. For example, cosmetics containing collagen for the purpose of preventing the occurrence of wrinkles have been used, but no sufficient effect has been obtained. It is also known that astringents have a skin tightening effect, but the effects of astringents are only temporary local serum reduction and vasoconstriction, and cannot improve skin sagging and the like.

[0003] The present invention relates to a pharmaceutical or cosmetic product that improves skin elasticity, thereby effectively preventing and improving skin properties such as skin wrinkles, sagging, and abrasion, and imparting a firm skin feeling. The purpose is to provide.

[0004]

Means for Solving the Problems The present inventors have developed glyceryl ethers which have been mainly used as surfactants (JP-B-59-15159, JP-A-58-158).
No. 104624, JP-A-11-139957, etc.), a specific glyceryl ether derivative has the effect of improving skin elasticity, preventing skin wrinkles and sagging, and imparting a firm feeling. And found to be useful as a medicine or cosmetic.

That is, the present invention provides the following general formula (1)

[0006]

Embedded image

[Wherein, R represents an alkyl group or an alkenyl group having 8 to 30 carbon atoms, X ¹ and X ² are each a hydrogen atom, —SO ₃ M ¹ or —PO ₃ M ¹ M ² (where, M ¹ and M
² are the same or different and each represent a hydrogen atom, an alkali metal, an alkaline earth metal or an ammonium group;
¹ and X ² are not simultaneously hydrogen atoms). A skin elasticity improving agent and a skin tightening agent comprising the glyceryl ether derivative represented by the formula (1) as an active ingredient.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION In the glyceryl ether derivative represented by the general formula (1) of the present invention, R represents 8 to 30 carbon atoms.
In the case of showing a linear or branched alkyl group of
Preferred examples include those having 10 to 22 carbon atoms, specifically n
-Decyl, trimethyldecyl, n-undecyl, 2-heptylundecyl, n-dodecyl, n-tridecyl, n
-Tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, methylheptadecyl (methyl-branched isostearyl), n-nonadecyl, n-icosyl, n-docosyl, etc., among which n-dodecyl, Particularly preferred are n-octadecyl and methylheptadecyl (methyl-branched isostearyl).

When R represents a linear or branched alkenyl group having 8 to 30 carbon atoms, preferred examples thereof include those having 10 to 22 carbon atoms, specifically, 10-undecenyl and 9-octadecenyl ( Oleyl), 9,12-octadienyl, 13-docosenyl and the like.

X ¹ and X ² are each a hydrogen atom, —SO
₃ is M ¹ or -PO ₃ M ¹ M ^2, not simultaneously hydrogen atoms. That is, the glyceryl ether derivative of the present invention is a mono- or disulfate ester or a mono- or diphosphate ester, and these may be used alone or as a mixture. Further, when M ¹ and M ² are an alkali metal, an alkaline earth metal or an ammonio group, the glyceryl ether derivative of the present invention becomes a salt of a sulfate or a phosphate, and specifically, lithium, sodium And alkaline earth metal salts such as beryllium, magnesium and calcium, and quaternary ammonium salts. Preferred salts include sodium, potassium and quaternary ammonium salts.

Glyceryl ether derivative (1) of the present invention
Preferred examples of 1-dodecylglycerol-3
-Sulfuric acid, 1-octadecylglycerol-3-sulfuric acid, 1
-Isostearylglycerol-3-sulfate, 1-dodecylglycerol-2,3-disulfate, 1-decylglycerol-3-phosphate, 1-dodecylglycerol-3-phosphate, 1-tetradecylglycerol-3-phosphate Acid, 1
-Hexadecylglycerol-3-phosphate, 1-octadecylglycerol-3-phosphate, 1-isostearylglycerol-3-phosphate, 1-oleylglycerol-3-phosphate, 1-dodecylglycerol-2,3- Examples thereof include diphosphoric acid and the like, and pharmacologically acceptable salts thereof. Particularly, from the viewpoint of effect and productivity, 1-dodecylglycerol-3-sulfate, 1-dodecylglycerol-3-phosphate, 1-isostearyl Glycerol-3-phosphate is preferred. Among them, 1-isostearylglycerol-3-phosphate is a novel compound not described in the literature.

The glyceryl ether derivative (1) in the present invention can be produced based on a known synthesis method. For example, it can be obtained by sulfating or phosphorylating glyceryl ether. For the sulfation reaction, known sulfating agents such as fuming sulfuric acid, concentrated sulfuric acid, sulfamic acid, chlorosulfonic acid, sulfur trioxide, dioxane of sulfur trioxide, pyridine complex and the like can be used (Experimental Chemistry Lecture 19 Organic Compounds) Synthesis I P201-20
3). For the phosphorylation reaction, phosphorus oxychloride, polyphosphoric acid, water and phosphoric anhydride, phosphoric acid and phosphoric anhydride, and the like can be used (Experimental Chemistry Course Organic Compound Synthesis IP2
06-210).

The glyceryl ether derivative (1) thus obtained exhibits excellent skin elasticity improving effect and tightening effect as shown in Examples 1 and 2. Therefore, a medicine or cosmetic containing the same may cause external stimuli such as drying and ultraviolet rays, and various changes in skin properties caused by aging of the skin, for example, wrinkles, sagging, abrasion and loss of elasticity of the skin. It is effective as a skin elasticity improving agent or skin tightening agent, and is administered in the form of external preparations such as ointments and creams, oral preparations such as tablets, granules, capsules and solutions, and various injections. be able to.

Further, since the glyceryl ether derivative (1) has an excellent feeling in use, the skin elasticity improving agent or the skin tightening agent of the present invention may be used in the form of a medicated skin external preparation such as an ointment or a cosmetic skin external preparation. Contains emulsified cosmetics, cream,
It is particularly preferred to use in various forms such as emulsions, lotions, gels and the like. In this case, in addition to the glyceryl ether derivative, an oily base such as a vegetable oil or an animal oil generally used in such a form, an analgesic anti-inflammatory, an analgesic, a disinfectant,
Astringents, emollients, hormonal agents, vitamins, humectants, ultraviolet absorbers, alcohols, chelating agents, pH adjusters, preservatives, thickeners, pigments, fragrances, etc. that do not interfere with the effects of the present invention Can be appropriately blended. The blending amount of the glyceryl ether derivative (1) in the skin external preparation is
0.001 to 20% by weight, particularly 0.01 to 5% by weight is preferred.

The skin elasticity improving agent or skin tightening agent of the present invention may be a formulation containing ceramides, sphingosines, phospholipids, and an animal or plant extract or a general compound having physiological skin activity. it can. Here, as the ceramides, ceramides such as N-acetylsphingosine, N-octadecanoylsphingosine, N-hexadecanoylsphingosine, N-pentadecanoylsphingosine, and the like; N-octadecanoyl cerebroside, N-hexadecanoyl cerebroside , Cerebrosides such as N-pentadecanoyl cerebroside; gangliosides; and particularly, N-octadecanoyl sphingosine, N-hexadecanoyl sphingosine, N-
Pentadecanoyl sphingosine is preferred. The content of these ceramides in the external preparation for skin is 0.0% in the total composition.
It is preferably from 001 to 5% by weight, particularly preferably from 0.001 to 3% by weight.

Examples of sphingosines include 2-amino-4-octadecene-1,3-diol (sphingosine) and 2-amino-4-hexadecene-1,3.
-Diol, 2-amino-4-heptadecene-1,3-
Diols, 2-amino-4-tetradecene-1,3-diol, N-methyl-substituted sphingosine (N-methyl sphingosine, N, N-dimethyl sphingosine, etc.),
1,3,4-trihydroxy-2-aminooctadecane (phytosphingosine), 1,3,4-trihydroxy-2-aminohexadecane, sphingomyelin, sphingosine-1-phosphate and the like, particularly 2-amino -4-octadecene-1,3-diol (sphingosine), N-methyl-substituted sphingosine, 1,3,4-
Trihydroxy-2-aminooctadecane (phytosphingosine) is preferred. The amount of the sphingosine compound in the external preparation for skin is preferably 0.0001 to 5% by weight, particularly preferably 0.001 to 3% by weight in the whole composition.

Examples of phospholipids include 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine,
-Dipentadecanoyl-sn-glycero-3-phosphocholine, 1,2-dihexadecanoyl-sn-glycero-
3-phosphocholine, 1,2-ditetradecanoyl-sn
Phosphatidylcholine and lyso-isomers such as glycero-3-phosphocholine; 1,2-dioctadecanoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipentadecanoyl-sn-glycero-3-phosphoethanolamine 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine, phosphatidylethanolamine such as 1,2-ditetradecanoyl-sn-glycero-3-phosphoethanolamine and lyso-form;
2-dioctadecanoyl-sn-glycero-rac-
(1-glycerol), 1,2-diheptadecanoyl-
sn-glycero-rac- (1-glycerol), 1,
2-dihexadecanoyl-sn-glycero-rac-
(1-glycerol), 1,2-ditetradecanoyl-
phosphatidylglycerol and lyso-form such as sn-glycero-rac- (1-glycerol); phosphatidylserine and lyso-form; phosphatidylinositol and lyso-form, and the like, in particular, 1,2-dioctadecanoyl-sn-glycero- 3-phosphocholine, 1,2-dipentadecanoyl-sn-glycero-3-phosphocholine,
1,2-dihexadecanoyl-sn-glycero-3-phosphocholine, 1,2-dioctadecanoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipentadecanoyl-sn-glycero-3 -Phosphoethanolamine, 1,2-dihexadecanoyl-sn-glycero-
3-phosphoethanolamine, 1,2-dioctadecanoyl-sn-glycero-rac- (1-glycerol), 1,2-diheptadecanoyl-sn-glycero-
rac- (1-glycerol) and 1,2-dihexadecanoyl-sn-glycero-rac- (1-glycerol) are preferred. The content of these phospholipids in the external preparation for skin is 0.0001 to 5% by weight, especially 0.1 to 5% by weight in the whole composition.
001 to 3% by weight is preferred.

Animal and plant extracts having physiological skin activity include, for example, wrinkle improving effect, whitening effect, anti-inflammatory effect, antioxidant effect, blood circulation promoting effect, astringent effect, sebum secretion inhibiting effect,
An animal and plant extract having an acne-improving effect, a moisturizing effect, an antibacterial effect, and the like can be given. Examples of the animal and plant extracts having such skin physiological activity include seaweeds such as hibamata, makombu, swordfish, and asenyaku, hydrolyzed almonds, red grape, asunaro, arnica, aloe, artecho, nettle, inchinko, fennel, usbania, Agetsu, Emisoso, Dutch Capsicum, Forsythia, Obaaku, Hypericum perforatum, Orange, Ougon, Ouren, Barley, Cuckoo, Guyou, Chamomile, Cuckoo, Licorice, Kiwi, Kizitsu, Kina, Kingkinka, Cucumber, Goldfish, Kumazasa,
Burdock, Comfrey, Clara, Gentian, Comfrey, Salvia, Saishin, Sansho, Hawthorn, Shimotsukesou, Shinanoki, Peonies, Jujuy (Dokudami), Shokyo, Shobu, Shiitake, Jio, Japanese horsetail, Birch, Honeysuckle, Sugi, Sage , Senkyu, vegetation, hawthorn, assembly,
Sahakuhi, daisies, tomatoes, cloves, chimpanzees, calendula, capsicum, pepper, tounin, spruce, elderberry, carrot, garlic, nutmeg, hammerellis, hamaboufu, hiokikoshi, peppermint, button, bodaiju, hop, maroni-yokei , Loquat, buttonpi, brunn, mannenrow, melissa, yuzu, eucalyptus, mugwort, cornflower, ryocha, lemon, vetch, lavender, rosemary, funnel, valerium, whey protein, lactococci, yeast, beef placenta extract , Beef skin, royal jelly extract, cockscomb, crab shells (chitin, chitosan) and the like.

Among such animal and plant extracts, those having a wrinkle-reducing effect are particularly preferably hydrolyzed almond, age, hawthorn, ginger, birch, butterflies, scallop extracts, etc., and the skin of these animal and plant extracts is preferred. The amount added to the external preparation is 0.00
It is preferably from 0.01 to 20% by weight, particularly preferably from 0.001 to 5% by weight.

Among those having a whitening effect, in particular, chamomile, ryocha, cuckoo, chow, liquorice, loquat, spruce, carrot, peonies, sohakuhhi, asenyaku, ogon, aloe, altea, shimotsusou,
Dutch mustard, kina, comfrey, rosemary, funnel, whey (milk semen) protein, yeast, placenta extract, and the like are preferred. The amount of these animal and plant extracts to be added to the skin external preparation is 0.1% in the total composition. 0001-20% by weight, especially 0.0
It is preferably from 0.01 to 5% by weight.

Among those having an anti-inflammatory effect, in particular, asunaro, aloe, ginkgo, osvenian oyster, oak,
Giant gourd, oak, orange, ginger, chamomile,
Licorice, Gentian, Pheasant, Agrimony, Kumazasa, Gentian, Comfrey, Hawthorn, Psychine, Birch, Horsetail, Tokinsenka, Carrot, Hamamelis, Chikoshi, Peppermint, Button, Marronnier Extract, etc. The amount added to the agent is preferably 0.0001 to 20% by weight, particularly preferably 0.001 to 5% by weight, based on the total composition.

As those having an antioxidant effect, in particular, extracts of Arnica, Ginkgo, Emperor, Hypericum perforatum, Salvia, Salamander, Sage, Assemblage, Tokinsenka, Hamamelis, Hamabofu, Bodaiju, Marronnier extract and the like are preferable. The amount added to the external preparation for skin is 0.0001 to 20% by weight in the total composition,
Particularly, 0.001 to 5% by weight is preferable.

As those having an astringent effect and a skin tightening effect, in particular, seaweeds such as hibamata, makombu, swordfish, and asenya, red grape, nettle, inchinko, age, oakaku, hypericum, gypsy,
Kina, goldfish, kiwi, gentian, salvia, horsetail, horsetail, sycamore, pomegranate, linden, birch, elderberry, hamamelis, hops, horse chestnut, cornflower, lemon, astragalus extract, and the like are preferable. Is 0.0001 to 20% by weight, especially 0.0
It is preferably from 0.01 to 5% by weight.

Among those having a blood circulation promoting effect, in particular, Dutch pepper, Clara, Sansho, Peony, Shokyo, Shobu, Senkyu, Assemble, Horse chestnut, Clove, Tokinsenka, Capsicum,
Touki, tounin, elderberry, garlic, mannen wax, melissa, yuzu, eucalyptus, mugwort, lavender extract and the like are preferable, and the blending amount of these animal and plant extracts to the external preparation for skin is 0.0001 to 20% by weight in the whole composition. And particularly preferably 0.001 to 5% by weight.

As those having an effect of inhibiting sebum secretion,
Particularly preferred are jujuya (dokudami), Japanese gourd, sage, and the like. The amount of these animal and plant extracts to be added to the external preparation for skin is 0.0001 to 20% by weight, especially 0.0
It is preferably from 0.01 to 5% by weight.

As those having an acne-improving effect, loquats, peonies, peanuts, honeysuckle and the like are particularly preferable. The amount of these animal and plant extracts to be added to the external preparation for skin is 0.0001 to 20% by weight in the whole composition. Especially 0.001
5% by weight is preferred.

Among those having a moisturizing effect, in particular, seaweeds such as hibamata, makombu and Ezoishige, and barley,
Orange, cuckoo, cucumber, burdock, shiitake mushroom, scallop, diatom, tomato, brawn, yeast, bovine skin, whey (milk semen) protein, royal jelly extract, cockscomb, lactococci, crab shell (chitin, chitosan) and the like are preferable, The amount of these animal and plant extracts to be added to the external preparation for skin is 0.0001 to 20% by weight, particularly 0.001 to 20% by weight in the whole composition.
5% by weight is preferred.

As those having an antibacterial effect, in particular, nutmeg, zinnia, edifice, tea, clove, chimney, fennel and the like are preferable. The amount of these animal and plant extracts to be added to the skin external preparation is 0.1% in the total composition. 0001-2
0% by weight, particularly preferably 0.001 to 5% by weight.

Such an animal or plant extract can be used alone or in combination of two or more, and the total amount of the extract is 0.00%.
01 to 20% by weight (% by weight of the combined extract), particularly preferably 0.001 to 5%, is highly effective in improving wrinkles, whitening, anti-inflammatory, antioxidant, blood circulation, astringent, and skin tightening. , Sebum secretion inhibiting effect, acne improving effect, moisturizing effect, antibacterial effect and the like are obtained.

Further, those having a wrinkle improving effect include retinoic acid and its esters, retinol and its esters, retinal, α-hydroxy acid and its esters, N-acetylcysteine and the like. In particular, retinal, α-Hydroxy acids and esters thereof are preferred, and the amount of these added to the external preparation for skin is preferably 0.0001 to 5% by weight, more preferably 0.001 to 3% by weight, based on the total composition.

Examples of those having a whitening effect include hydroquinone and its derivatives, kojic acid and its derivatives, ascorbic acid and its derivatives, arbutin, tocopherol sorbate, sodium isoferrate, sorbohydroxamic acid, catechol glycosides, ellagic acid. And the like, in particular, kojic acid and its derivatives, ascorbic acid and its derivatives, arbutin and tocopherol sorbate are preferred, and the amount of these added to the external preparation for skin is 0.0001 to 5% by weight in the whole composition, particularly 0.001 to 3% by weight
Is preferred.

Examples of those having an anti-inflammatory effect include glycyrrhizic acid and glycyrrhizic acid derivatives, allantoin, guaiazulene, γ-oryzanol, epsilon aminocaproic acid, lysozyme chloride, l-menthol, etc., and particularly glycyrrhizic acid and glycyrrhizic acid derivatives, allantoin , Guaiazulene, γ-oryzanol, etc., and the amount of these added to the external preparation for skin is preferably 0.0001 to 5% by weight, more preferably 0.001 to 3% by weight, based on the total composition.

Examples of those having an antioxidant effect include tocopherol, tocopherol acetate, β-carotene, tannic acid, epicarocatechin gallate, glutathione, superoxide dismutase (SOD), ferulic acid and the like. In particular, tocopherol, tocopherol acetate, β
Carotene, tannic acid, and the like are preferable, and the amount of these in the external preparation for skin is 0.0001 to 5% by weight in the whole composition.
In particular, 0.001 to 3% by weight is preferable.

Examples of those having an astringent effect and a skin tightening effect include zinc oxide and zinc sulfocarbonate.
The amount added to these skin external preparations is 0.00% in the total composition.
It is preferably from 0.01 to 5% by weight, particularly preferably from 0.001 to 3% by weight.

Examples of those having a blood circulation promoting effect include nicotinic acid esters such as nicotinic acid tocopherol, nicotinic acid amide and methyl nicotinic acid. Particularly preferred are tocopherol nicotinate, nicotinic acid amide and methyl nicotinic acid. The amount blended into the skin external preparation is
0.0001 to 5% by weight in the total composition, especially 0.001 to
3% by weight is preferred.

As those having the effect of inhibiting sebum secretion,
Vitamin B6, persimmon tannin, 10-hydroxydecenoic acid and salts thereof, and the like are particularly preferable, and 10-hydroxydecenoic acid and salts thereof are preferable. 5% by weight, in particular 0.0
0 to 1% by weight is preferred.

Examples of those having an acne-improving effect include sulfur, salicylic acid, benzoyl peroxide, N- (2,3-xylyl) anthranilic acid ester derivatives, retinoic acid and esters thereof, and particularly sulfur and salicylic acid. Preferably, the amount added to these external preparations for skin is 0.0001 to 5% by weight, particularly 0.001 to 3% by weight, based on the total composition.

Examples of those having a moisturizing effect include vitamin F, diacylglycerin, water-soluble collagen, hyaluronic acid, etc., and particularly preferred are diacylglycerin, water-soluble collagen, hyaluronic acid and the like. The compounding amount is preferably 0.01 to 20% by weight, particularly preferably 0.1 to 10% by weight in the whole composition.

Examples of those having an antibacterial effect include hinokitiol, pyroctone olamine and the like, and the amount of these added to the external preparation for skin is 0.001 to 3% by weight in the total composition, particularly 0.1 to 0.1% by weight. 2% by weight is preferred.

Such a wrinkle improving agent, a whitening agent, an anti-inflammatory agent,
The antioxidant, the blood circulation promoter, the astringent, the skin tightening agent, the sebum secretion inhibitor, and the acne improving agent can be used alone or in combination of two or more.
When 5% by weight, particularly preferably 0.001 to 3% is added, a high wrinkle improvement effect can be obtained. The humectant may be used alone or in combination of two or more, and preferably 0.01 to 20% by weight, particularly preferably 0.1 to 10% by weight in the whole composition.
%, A high moisturizing effect can be obtained. In addition, antibacterial agents can be used alone or in combination of two or more,
0.001 to 3% by weight in the total composition, particularly preferably 0.1% by weight.
A high antibacterial effect can be obtained by adding 1 to 2%.

Further, these compounds can be used in combination with one or more of the above-mentioned animal and plant extracts and the like, and 0.0001 to 20% by weight in the total composition (% by weight of the combined extract). ), Particularly preferably 0.001 to 5%
When blended, higher wrinkle improving effect, whitening effect, anti-inflammatory effect, antioxidant effect, blood circulation promoting effect, astringent effect, skin tightening effect, sebum secretion suppressing effect, acne improving effect, moisturizing effect, and antibacterial effect can be obtained.

[0042]

EXAMPLES Preparation Example 1 Preparation of 1-dodecylglycerol-3-sulfate sodium salt (compound 1) 10 g (0.039 mol) of dodecylglyceryl ether
Was dissolved in anhydrous pyridine, and after cooling with ice, 6.2 g (0.039 mol) of sulfur trioxide / pyridine complex was added.
Stirred for hours. Thereafter, the mixture was stirred at room temperature for 12 hours, and distilled water and pyridine were distilled off.
(0.039 mol) and lyophilized to give 14.2 g of 1-dodecylglycerol-3-sulfate sodium salt (HP
LC analysis purity 約 90%).

Production Example 2 Production of 1-octadecylglycerol-3-sulfate sodium salt (compound 2) Production was performed using octadecylglyceryl ether in the same manner as in Production Example 1 to obtain 1-octadecylglycerol ether.
3-Sodium sulfate was obtained.

Production Example 3 Production of 1-isostearylglycerol-3-sulfate (compound 3) Production was carried out in the same manner as in Production Example 1 using isostearylglyceryl ether, and sodium 1-isostearylglycerol-3-sulfate was produced. I got

Production Example 4 Preparation of 1-decylglycerol-3-phosphate disodium salt (compound 4) 5 g (0.022 mol) of decylglyceryl ether was dissolved in hexane, and the mixture was mixed with 105% polyphosphoric acid at 50.degree.
g (0.108 mol) was added, and the mixture was stirred at 70 ° C. for 12 hours. Thereafter, 10 g of distilled water was added, and the mixture was further stirred for 3 hours.
After cooling, ethanol was added and the aqueous layer was separated. After concentrating the organic layer, purified water and sodium hydroxide were added and freeze-dried to obtain 7.3 g of 1-decylglycerol-3-phosphate disodium salt (HPLC analysis purity: about 70%).

Production Example 5 Production of 1-dodecylglycerol-3-phosphate disodium salt (compound 5) Production was conducted using dodecylglyceryl ether in the same manner as in Production Example 4 to obtain 1-dodecylglycerol-3-phosphate. The disodium salt was obtained.

Production Example 6 Production of 1-tetradecylglycerol-3-phosphate disodium salt (compound 6) Production was performed using tetradecylglyceryl ether in the same manner as in Production Example 4 to obtain 1-tetradecylglycerol-
3-phosphate disodium salt was obtained.

Production Example 7 Production of 1-hexadecylglycerol-3-phosphate disodium salt (compound 7) Production was performed using hexadecylglyceryl ether in the same manner as in Production Example 4 to give 1-hexadecylglycerol-
3-phosphate disodium salt was obtained.

Production Example 8 Production of 1-octadecylglycerol-3-phosphate disodium salt (compound 8) Production was carried out using octadecylglyceryl ether in the same manner as in Production Example 4 to give 1-octadecylglycerol-
3-phosphate disodium salt was obtained.

Production Example 9 Production of 1-isostearylglycerol-3-phosphate disodium salt (compound 9) Production was carried out using isostearylglyceryl ether in the same manner as in Production Example 4 to obtain 1-isostearylglycerol-3. -A disodium phosphate salt is obtained.

Production Example 10 Production of 1-oleylglycerol-3-phosphate disodium salt (compound 10) Production was carried out using oleylglyceryl ether in the same manner as in Production Example 4 to obtain 1-oleylglycerol-3-phosphate. The disodium salt was obtained.

Production Example 11 Production of 1-dodecylglycerol-2,3-disulfate sodium salt (compound 11) 10 g (0.039 mol) of dodecylglyceryl ether
Was dissolved in anhydrous pyridine, 31 g (0.195 mol) of sulfur trioxide / pyridine complex was added at room temperature, and the mixture was stirred at 70 ° C. for 1 hour. After pyridine is distilled off, purified water and sodium hydroxide are added, and the mixture is freeze-dried to give 1-dodecylglycerol-
11.5 g of 2,3-disulfate sodium salt was obtained.

Production Example 12 Production of 1-dodecylglycerol-2,3-diphosphate disodium salt (compound 12) 2 g (7.7 mmol) of dodecylglyceryl ether was dissolved in anhydrous pyridine, and diphenylphosphoric acid chloride was added at -20.degree. 10.4 g (0.0387 mol) was added dropwise over 1 hour. After stirring at the same temperature for 48 hours, ion-exchanged water was added to 0.1 ml.
75 g was added and pyridine was distilled off under reduced pressure. The residue was extracted with ether, washed successively with dilute hydrochloric acid and water. After distilling off the ether, the residue was subjected to column chromatography to give a reaction intermediate 2.
63 g were obtained. Next, 0.5 g of reaction intermediate (0.69 mm
ol) was dissolved in acetic acid, 0.2 g of platinum oxide was added, and the mixture was stirred at room temperature for 3 hours while blowing hydrogen. Platinum oxide was filtered off, acetic acid was distilled off, purified water and sodium hydroxide were added, and the mixture was freeze-dried, washed with methanol, and 0.33 g of 1-dodecylglycerol-2,3-diphosphate disodium salt.
I got Table 1 shows the spectral data of Compounds 1 to 12.

[0054]

[Table 1]

Example 1 Measurement of Collagen Gel Tightening-Promoting Ability The fibroid-embedded collagen gel, which is a dermis model, was measured for its tightening-promoting ability. Collagen gel is described in the literature `` J.
Cell Science, 102, 315 (1992) "or" J. Invest. D
ermatol, 93, 792 (1989) ". That is, HEPE was added to a collagen gel solution (tapel-A (3.0 mg / mL, pH = 3) manufactured by Nitta Gelatin Co., Ltd.) under ice cooling.
S, (250 mM) 0.05N sodium hydroxide solution, DMEM (GIBCO DMEM, Iow glucose) 5-fold concentrated solution, FCS (2%, Fatal Calf Serum) and purified water were added, and finally human dermal fibroblasts After adding a suspension (derived from human foreskin) and thoroughly stirring to remove air bubbles, 600 μL of each well was poured into a 24-well dish, and immediately heated to 37 ° C. in an incubator to gel. 3,4
After time, 1 mL of serum-free DMEM medium was added to each well,
The periphery was peeled off from the dish to make it float. Eighteen hours later, the medium was replaced with a serum-free DMEM medium containing 100 to 10 µM of the test substance, and the cells were further incubated for 48 hours. Gel volume measurement is described in the literature (J. Cell Sc
ience, 102, 315 (1992)). That is, 10% formalin fixation (4 ° C, 24 hours)
Then, the surface tension of the water was adjusted using Triton X100 (manufactured by Wako Pure Chemical Industries, Ltd.) (1
%), And the weight was measured.

Table 2 shows the measurement results of the relative volume of each compound when the volume of the control was taken as 100%.

[0057]

[Table 2]

As is clear from Table 2, the action of the glyceryl ether derivatives (compounds 1 to 8) of the present invention reduced the volume of the collagen gel and promoted the tightening of the collagen gel.

Example 2 Evaluation of Rat Skin Elasticity Improving (Tightening) Effect A 2% solution of Compounds 1 and 4 (solvent: 10% ethanol) was applied to the entire back skin of HR rats (WBN / ILA-HT, 7 weeks old). 1
It was applied once or twice a day, a total of 7-8 times a week, in a spray form of 0.7 ml each. A 10% ethanol solution was used as a control. Two weeks later, under Nembutal anesthesia, the skin elasticity of the skin at the center and back of the midline slightly to the right was measured using a cute meter (CUTOMETER SEM474, Courage + Khaza).
It was measured using ka). Suction pressure 100hpa, suction time 5
The instantaneous elastic displacement Ue, instantaneous recovery displacement Ur, and final displacement Uf were measured in seconds and a release time of 2 seconds. The effect of skin tightening was observed by changing the elasticity of the skin. Ue is an index of elasticity and Uf is an index of flexibility. Both of them decrease with aging on the face and the like, and decrease with swelling of the skin. Thus, an increase in these values is an indicator of a tighter skin with more flexibility and elasticity. Ur is also an index of elasticity, and decreases when the skin is sagged or swollen. Similarly, an increase in this value is an indicator that the skin is more elastic, firmer and tighter. Furthermore, Ur / Uf also
It is an index of the elasticity of the skin, and decreases when the skin sags or bulges like Ur. Further, it is known that Ur / Uf is lowered by aging regardless of the face or body part, and is an important indicator of sagging. The results are shown in Tables 3 and 4.

[0060]

[Table 3]

[0061]

[Table 4]

From Tables 3 and 4, it was confirmed that the application of Compounds 1 and 4 increased the elasticity of the skin and showed a skin tightening effect.

Formulation Example 1 Lotion A lotion having the following formulation was prepared by a conventional method. (Components) (% by weight) Compound 1 2.0 Compound 6 0.5 Glycerin 5.0 Dipropylene glycol 4.0 Polyoxyethylene isocetyl ether (20EO) 1.0 Clove extract Spruce extract 1.0 Asnaro extract 0.0 5 Ethanol 8.0 Preservative qs Perfume qs Buffer qs Purified water balance

Formulation Example 2 Lotion A lotion having the following formulation was prepared by a conventional method. (Components) (% by weight) Compound 2 3.0 Compound 5 1.0 Glycerin 4.0 1,3-Propylene glycol 3.0 Polyoxyethylene isocetyl ether (20EO) 1.0 Hibamata extract 3.0 Sansha extract 1.0 Melissa extract 1.0 Ethanol 8.0 Preservative proper amount Perfume proper amount Buffer proper amount Purified water balance

Formulation Example 3 Cream (W / O) A cream having the following formulation was prepared by a conventional method. (Components) (% by weight) Compound 9 2.0 Compound 7 1.0 Microcrystalline wax 3.0 Lanolin 3.0 Vaseline 5.0 Squalane 9.0 Olive oil 12.0 Sorbitan sesquioleate 3.0 Poly trioleate Oxyethylene sorbitan (20EO) 3.0 Barley extract 2.0 Placenta extract 1.0 Arbutin 1.0 Kojic acid 1.0 Phosphatidylcholine 1.0 Flavor appropriate amount Buffer appropriate amount Purified water Balance

Formulation Example 4 Cream (O / W) A cream having the following formulation was prepared by a conventional method. (Components) (% by weight) Compound 5 2.5 Compound 1 0.3 Hardened coconut oil 6.0 Stearic acid 3.0 Cetanol 4.0 Vaseline 2.0 Squalane 8.0 Neopentyl glycol dicaprate 4.0 Monostearin Polyoxyethylene sorbitan acid (20EO) 2.3 Glycerin stearate 1.7 Glycerin 3.0 1,3-butylene glycol 7.0 Glycyrrhizic acid 1.0 Tocopherol 2.0 Hyaluronic acid 1.0 Dutch glass extract 3.0 Aloe extract 1.0 Carrot extract 1.0 Preservatives qs Perfume qs Purified water balance

Formulation Example 5 Emulsion An emulsion having the following formulation was prepared by an ordinary method. (Components) (% by weight) Compound 1 1.5 Compound 7 0.3 Palmitic acid 0.5 Olive oil 2.0 Cetanol 1.0 Jojoba oil 5.0 Monohexadecyl phosphate sodium salt 2.0 Sorbitan monostearate 0 5.5 Glycerin 15.0 Ethanol 5.0 Ascorbic acid 0.5 Tocopherol nicotinate 1.0 Ginger extract 2.0 Ginkgo extract 2.0 Preservatives Appropriate amount Perfume Appropriate amount Purified water Balance

Formulation Example 6 Emulsion An emulsion having the following formulation was prepared by an ordinary method. (Components) (% by weight) Compound 9 2.0 Compound 3 0.8 Compound 1 1.2 Stearic acid 1.0 Cholesteryl isostearate 2.0 Jojoba oil 4.0 Squalane 8.0 Sorbitan sesquioleate 0.8 Mono Polyoxyethylene sorbitan stearate (20EO) 0.5 1,3-butylene glycol 5.0 L-arginine 0.4 Carboxyvinyl polymer 0.2 Carrot extract 1.5 Asenyaku extract 0.5 Shiitake extract 0.5 Macomb Extract 0.5 Ceramide 1.0 Preservative proper amount Perfume proper amount Purified water balance

Formulation Example 7 Pack A pack having the following formulation was prepared by an ordinary method. (Components) (% by weight) Compound 5 3.0 Compound 8 2.0 Polyvinyl alcohol 14.0 Sodium carboxymethylcellulose 3.0 Xanthan gum 1.0 Glycerin 3.0 1,3-butylene glycol 2.0 Polyoxyethylene Hardened castor oil (50EO) 0.5 Touki extract 0.5 Whey extract 2.0 Astragalus extract 0.5 Sphingosine 0.2 Preservatives proper amount Perfume proper amount Purified water balance

[0070]

The skin elasticity improving agent and the skin tightening agent of the present invention exhibit the effect of improving the skin elasticity and the effect of tightening the skin, and cause wrinkles, sagging, abrasion and loss of elasticity, dullness, dullness of the skin caused by various causes. It is useful as a medicine or cosmetic for effectively preventing and improving changes in skin properties such as spot freckles.

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Tsutomu Fujimura 2606 Akabane, Kaigamachi, Haga-gun, Tochigi Prefecture F-term (reference) 4C083 AA072 AA112 AA122 AC012 AC022 AC072 AC102 AC122 AC181 AC182 AC242 AC392 AC422 AC442 AC542 AC582 AC642 AC692 AC781 AC782 AC842 AC901 AC902 AD042 AD092 AD112 AD272 AD332 AD352 AD392 AD492 AD512 AD532 AD642 BB51 CC04 CC05 CC07 DD23 DD31 DD32 EE12 FF01

Claims (3)

[Claims] 1. The following general formula (1): [Wherein, R represents an alkyl group or an alkenyl group having 8 to 30 carbon atoms, X ¹ and X ² each represent a hydrogen atom, —SO ₃
M ¹ or —PO ₃ M ¹ M ² (where M ¹ and M ² are the same or different and represent a hydrogen atom, an alkali metal, an alkaline earth metal or an ammonium group) (provided that X ¹ and X ² Are not simultaneously hydrogen atoms). ] A skin elasticity improving agent comprising the glyceryl ether derivative represented by the formula (1) as an active ingredient. 2. The skin elasticity improving agent according to claim 1, which prevents and improves wrinkles and sagging of the skin. 3. A skin tightening agent comprising the glyceryl ether derivative according to claim 1 as an active ingredient.