JP2001031549A - Agent for reconstructing dermal collagen fiber bundle and cosmetic containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject reconstruction agent which has an action on damaged and disordered structure-having skin to reconstruct its structure, by including a specific adenine derivative. SOLUTION: This agent for reconstructing dermal collagen fiber bundles contains an adenine derivative of the formula [R1 is a 4 to 16C unsaturated hydrocarbon which may contain oxygen in the substituent; R2 is H, a saccharide residue or a 1 to 4C alkyl; R3 is H, an (acylated) saccharide residue or a 1 to 4C alkyl; the dotted line is a combination of a double bond with a single bond] and/or its physiologically acceptable salt. The compound of the formula is preferably either of kinetin, trans-zeatin, cis-zeatin, trans-zeatin riboside and cis-trans-zeatin riboside. The compound of the formula may be extracted from a plant or synthesized from adenine and so on as raw materials. When the reconstructing agent is used for skin preparations for external use, the content of the reconstructing agent is preferably 0.001 to 5 wt.%, especially preferably 0.005 to 1 wt.%.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a cosmetic, and more particularly, to a cosmetic suitable for correcting disorder of skin structure.

[0002]

2. Description of the Related Art The skin is an important organ that separates a living body from the outside world, and is therefore more susceptible to damage than the outside world.
Causes of injury include damage or polymerization / crosslinking of skin components due to light or radical generation, damage and death of constituent cells,
For this reason, the skin is regularly accumulated with traces of such external injuries, and it is said that such phenomena are one of the causes of the skin becoming less beautiful as it gets older. .
In addition to such a secular change, it is said that keloid formation
There are not a few morphological changes in the skin structure due to injury, such as abnormal formation of granulation. At present, there is no known means for correcting a morphological change of the skin structure caused by an injury to the skin from the outside, except by a surgical operation.

On the other hand, compounds and / or salts represented by the following general formula (I) are known as plant hormones,
It is not known at all that it has a restructuring effect on the collagen fiber bundle of the dermis, and therefore, cosmetics containing such components can be applied to damaged skin whose structure has been disordered. It has not been known at all that it acts to regenerate the skin structure.

[0004]

SUMMARY OF THE INVENTION The present invention has been made under such circumstances, and has a function of regenerating a skin structure by acting on skin whose structure has been disordered due to injury. The task is to provide

[0005]

In view of such a situation, the present inventors have intensively researched for a cosmetic having a cosmetic having an action of regenerating the skin structure. It has been found that a cosmetic containing the compound represented by the general formula (I) and / or a salt thereof has such an effect, and has completed the invention. Hereinafter, the present invention will be described in detail focusing on embodiments.

[0006]

Embedded image General formula (I) (wherein, R1 represents a hydrocarbon group containing an unsaturated bond having 4 to 16 carbon atoms which may contain an oxygen atom in the substituent, and R2 represents a bonding group represented by R3. If you do not have
R3 represents a hydrogen atom, a sugar residue or an alkyl group having 1 to 4 carbon atoms, and R3 has no bonding group in R2;
Represents a hydrogen atom, a sugar residue which may be acylated, or an alkyl group having 1 to 4 carbon atoms, and a bond shown by a dotted line represents a combination of one double bond and one single bond. )

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION (1) Agent for Reconstructing Collagen Fiber Bundle Structure of Dermis of the Present Invention The agent for reconstructing collagen fiber bundle structure of dermis of the present invention comprises a compound represented by the above general formula (I) and And / or a physiologically acceptable salt thereof. Here, in the formula, R1 represents a hydrocarbon group containing an unsaturated bond having 4 to 16 carbon atoms which may contain an oxygen atom in the substituent, and the form of the oxygen atom contained is a hydroxyl group, an acyloxy group, or the like. Groups, carboxyl groups, ether groups (alkyloxy groups) and the like are preferred. The hydrocarbon group may be an aliphatic group or an aromatic group. For example, if the group is an aliphatic group, a hydroxypentenyl group, a hydroxyhexenyl group, a methoxypentenyl group,
Preferred examples include an ethoxypentenyl group, a normal butyloxypentenyl group, a phenoxypentenyl group, and a furfuryl group. Further, only one of the groups represented by R2 or R3 exists. This is because adenines form a tartomer, and it is known that they enter the 7-position and the 9-position, and a hydrogen atom or a substituent only enters either of them. The choice of the presence of R2 or R3 determines the combination of double and single bonds represented by the dotted lines in the formula. Specific examples of the type of R2 and R3 include a hydrogen atom and an acylated group.
A sugar residue such as a ribose residue, a glucose residue or an arabinose residue, a methyl group, an ethyl group, a normal propyl group, an isopropyl group, a normal butyl group, a secondary butyl group, a tertiary butyl group and the like having 1 to 4 carbon atoms; Preferred examples include an alkyl group. As the acyl group that the sugar residue can have, one having 1 to 4 carbon atoms is preferable, and an acetyl group is particularly preferable. Among these, preferred are a hydrogen atom and a sugar residue, and among them, a hydrogen atom is particularly preferred from the viewpoint of efficacy. At this time, these groups are preferably attached at the position of R2. Specific examples of preferred compounds include transzeatin, ciszeatin, transzeatin riboside, ciszeatin riboside, isoseatin, kinetin, and physiologically acceptable salts thereof. Of these, transzeatin, ciszeatin, and kinetin are particularly preferred. These compounds can be extracted from plants or synthesized using adenine or the like as a raw material. When adenine is synthesized as a raw material, acetonitrile or the like is used as a solvent, and hydrogen on a nitrogen atom is substituted with a trimethylsilyl group using a silylating agent such as hexamethyldisilazane or trimethylsilyl chloride, and then substituted with a hydroxyl group or the like. It can be obtained by coupling a halide such as halogenated hydrocarbon or furfuryl chloride whose group is protected with an acetyl group or the like to a catalyst using a Lewis acid or the like, followed by deprotection using a base such as methanolic ammonia. . Further, these glycosides can be obtained by trimethylsilylating these compounds, coupling an acetylated form of the sugar, silver oxide or the like to a catalyst, and deprotecting. Many of such adenine derivatives are commercially available as reagents, and these can also be used. The agent for reconstructing the collagen fiber bundle structure of the dermis of the present invention thus obtained has an action of reconstructing the disorder of the collagen fiber bundle structure of the dermis and restoring it to a normal structure. Prevention, improvement or treatment of a change in skin morphology caused by collapse of the collagen fiber bundle inside the dermis by administering the reconstituting agent of the dermal collagen fiber bundle structure of the present invention in a skin external preparation such as cosmetics. You can do it. When the present invention is used by being contained in such an external preparation for skin, the content is preferably 0.001 to 5% by weight, more preferably 0.005 to 1% by weight.

[0008]

Embedded image Transzeatin

[0009]

Embedded image Ciszeatin

[0010]

Embedded image Transzeatin riboside (where Ribo represents a ribose residue)

[0011]

Embedded image Ciszeatin riboside (where Ribo represents a ribose residue)

[0012]

Embedded image Isoseatin

[0013]

Embedded image Kinetin

(2) Cosmetic of the Present Invention The cosmetic of the present invention contains one or two or more selected from the above-mentioned agents for reconstructing the collagen fiber bundle structure of the dermis, and suppresses morphological changes of the skin. And / or used for improvement. Here, the change in skin morphology suppressed and / or improved by the cosmetic of the present invention refers to a change in skin morphology visible on the skin caused by disorder of the collagen fiber bundle structure of the dermis. Changes in skin morphology include, for example, loss of elasticity of the skin due to excessive irradiation of light or accumulation of irradiation, roughening of the surface structure, loss of elasticity of the skin due to accumulation of stimuli over time, generation of keloids, and the like. In addition, wrinkles are also applied if they are caused by disturbance of the collagen fiber bundle structure of the dermis, because the action of the restructuring agent for the collagen fiber bundle structure of the dermis of the present invention can suppress or improve the formation thereof, and therefore it is applied. be able to. The cosmetic of the present invention can be applied in any dosage form without any particular limitation as long as it is usually used for such skin care, for example, lotion, milky lotion, cream, pack Cosmetic products, basic cosmetics such as essence cosmetics and the like, makeup cosmetics such as under makeup and foundation, hair cosmetics, washing cosmetics, etc. can be preferably exemplified. Among these, it is preferable to apply the basic cosmetics. Particularly preferred. This is because the place of such an effect of the cosmetic is the same as that of the agent for reconstructing the collagen fiber bundle structure of the dermis of the present invention, and an additive or synergistic effect can be obtained. is there.

The cosmetic of the present invention may contain, in addition to the above-mentioned essential component, the agent for reconstructing the collagen fiber bundle structure of the dermis of the present invention, any component usually used in cosmetics. Examples of the optional component include hydrocarbons such as squalane, petrolatum, and microcrystalline wax, jojoba oil, carnauba wax, esters such as octyldodecyl oleate, and triglycerides such as olive oil, tallow, and coconut oil. Fatty acids such as stearic acid, oleic acid, and ritinoleic acid; higher alcohols such as oleyl alcohol, stearyl alcohol and octyl dodecanol; anionic surfactants such as sulfosuccinates and sodium polyoxyethylene alkyl sulfate; and alkyl betaine salts. Amphoteric surfactants, cationic surfactants such as dialkylammonium salts, sorbitan fatty acid esters, fatty acid monoglycerides, their polyoxyethylene adducts, polyoxyethylene alkyl ethers, polyoxyethylene Nonionic surfactants such as alkylene fatty acid esters, polyethylene glycol,
Preferred examples include polyhydric alcohols such as glycerin and 1,3-butanediol, thickening / gelling agents, antioxidants, ultraviolet absorbers, coloring agents, preservatives, powders, and various medicinal ingredients. Particularly preferred among these are ursolic acid and its esters, sodium hyaluronate, and the like, which have a useful effect for reconstructing the collagen fiber bundle of the dermis, a favorable effect for improving the skin, and a favorable effect for complementing the skin function. Mucopolysaccharides, polysulfated polysaccharides such as heparin-like substances, trehalose and its derivatives such as trehalose and sodium sulfated trehalose, steroids and their glycosides,
A methacryloyloxyethoxyphosphatidylcholine polymer can be preferably exemplified. The content of these is suitably about 0.001 to 0.5% by weight. The cosmetic of the present invention can be produced by treating such components according to a conventional method. Since the cosmetic of the present invention has a function of suppressing and improving skin morphological changes caused by disorder of dermal collagen fiber bundles by the action of a restructuring agent of dermal collagen fiber bundle structure, such morphological changes It is preferably used for prevention or improvement.

[0016]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but it goes without saying that the present invention is not limited only to these Examples.

Example 1 Using a hairless mouse-cumulative light irradiation model, the effect of the agent for reconstructing the collagen fiber bundle structure of the dermis of the present invention was examined. Hairless mouse (Skh:
The back of HR-1, female, 8 weeks old) was irradiated with ultraviolet rays (Toshiba SE lamp, 60 mJ / cm 2) for 10 weeks every day to prepare a model of damage to the optical fiber bundle structure. The animals were divided into groups of 3 animals each, and a 50% concentration of each test substance 0.1% was placed on the back.
A solution using an aqueous ethanol solution as a solvent was applied for 2 weeks.
Only a 50% aqueous ethanol solution was applied to the control group. Blanks were not irradiated or sampled. 24 hours after the last administration, the skin was collected and treated according to the NaOH method to prepare a specimen. These were observed with an electron microscope, and the degree of disorder of the collagen fiber bundle structure of the dermis was ranked 0: abnormal collagen fiber bundle structure or collapse of the fiber bundle structure was observed throughout the observation region. Rank 1: fibers were found in the majority region. Degradation of the structure of the bundle or transition to structural abnormality is recognized. Rank 2: Disruption or abnormality of the fiber bundle structure is partially observed, but almost normal fiber bundle structure is recognized as a whole. Rank 3: Totally normal Judgment was made based on the standard of the fiber bundle structure. The results are shown in Table 1 as the number of occurrences. FIG. 1 shows kinetin rank 3.
FIG. 2 shows an electron micrograph of Comparative Example 1, and FIG. This shows that the agent for reconstructing the fiber bundle structure of the dermis of the present invention is excellent in the effect of correcting the disorder of the collagen fiber bundle structure.

[0018]

[Table 1]

Example 2 A damaged keloid model was prepared using a Hartley white guinea pig, and the effect of the agent for reconstructing the collagen fiber bundle structure of the dermis of the present invention on the damaged keloid was examined. That is, the back of the guinea pig was shaved, 0.1 ml of an emulsion prepared with incomplete Freund's adjuvant and water was injected intradermally once a day into eight places once a day, and this operation was performed for 10 days to prepare an injury keloid. . Fourteen days after the last administration, 0.01 ml of a sample was applied to one keloid once a day (the sample was prepared in Example 1).
(Same as)) transdermally for 10 days. Compared with the control, these keloid healing levels were as follows: Rank 0: comparable keloid to the control, Rank 1: slightly less keloid than the control, rank 2: considerably less keloid than the control, rank 3: no keloid formation Judgment was made based on the same standard as the blank site. The results are shown in Table 2 as the number of occurrences. This shows that the agent for reconstructing the collagen fiber bundle structure of the dermis of the present invention is excellent in the effect of improving skin morphological changes caused by disorder of the fiber bundle such as keloid.

[0020]

[Table 2]

<Examples 3 to 8> Lotions were prepared according to the following formulation. That is, the formulation components were heated and solubilized at 80 ° C., and cooled to obtain a lotion. Glycerin 5 parts by weight 1,3-butanediol 5 parts by weight Fragrance 0.1 part by weight Methylparaben 0.1 part by weight Polyoxyethylene (60) hydrogenated castor oil 0.1 part by weight Sodium hyaluronate 0.1 part by weight methacrylyloxyethoxy Josfatidylcholine 0.1 part by weight Heparin-like substance 0.1 part by weight Reconstructive agent for collagen fiber bundle structure of dermis of the present invention * 0.1 part by weight 5.3 parts by weight of ethanol 84 parts by weight of water * Table 3 Show details.

[0022]

[Table 3]

<Example 9> The lotion of Examples 3 to 8 and the kinetin of the lotion of Example 3 were used using a total of 70 panelists, each group consisting of 10 panelists suffering from the loss of skin elasticity caused by excessive light irradiation. Was replaced with water for one month, and the presence or absence of improvement in loss of elasticity was examined by a questionnaire. Table 4 shows the results as effective rates. This indicates that the cosmetic of the present invention has an action of improving the change in skin morphology caused by the disorder of the structure of the collagen fiber bundle.

[0024]

[Table 4]

[0025]

According to the present invention, it is possible to provide a cosmetic having an action of regenerating the skin structure by acting on the skin whose structure has been damaged due to injury.

[Brief description of the drawings]

FIG. 1 is an electron micrograph (a substitute for a drawing) of rank 3 of kinetin treatment.

FIG. 2 is an electron micrograph (a substitute for a drawing) of Rank 0 in the control of Example 1.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 31/70 620 A61K 31/70 620 // C07D 473/34 351 C07D 473/34 351 C07H 19/167 C07H 19/167 (72) Mitsuo Kawai Inventor F-term (reference) 4C057 BB02 CC03 DD01 LL31 4C083 AC102 AC122 AC432 AC482 AC792 AC851 AC852 AD201 AD202 AD312 AD332 BB60 CC01 CC04 EE12 4C0 AA01 CB07 EA11 GA02 MA04 NA14 ZA89 ZB21

Claims (5)

[Claims] 1. An agent for reconstructing a collagen fiber bundle structure of the dermis, comprising an adenine derivative represented by the following general formula (I) and / or a physiologically acceptable salt thereof: Embedded image General formula (I) (wherein, R1 represents a hydrocarbon group containing an unsaturated bond having 4 to 16 carbon atoms which may contain an oxygen atom in the substituent, and R2 represents a bonding group represented by R3. If you do not have
R3 represents a hydrogen atom, a sugar residue or an alkyl group having 1 to 4 carbon atoms, and R3 has no bonding group in R2;
Represents a hydrogen atom, a sugar residue which may be acylated, or an alkyl group having 1 to 4 carbon atoms, and a bond shown by a dotted line represents a combination of one double bond and one single bond. ) 2. The compound represented by the general formula (I), which is any one of kinetin, transzeatin, ciszeatin, transzeatin riboside or ciszeatin riboside. 2. The agent for reconstructing collagen fiber bundle structure of the dermis according to item 1. 3. A cosmetic composition for regenerating a skin structure, comprising the agent for reconstructing the collagen fiber bundle structure of the dermis according to claim 1 or 2. 4. A cosmetic for regenerating a skin structure, comprising one or more compounds selected from the compound represented by the general formula (I) and a physiologically acceptable salt thereof. 5. The method according to claim 4, wherein the compound represented by the general formula (I) is any of kinetin, transzeatin, ciszeatin, transzeatin riboside or ciszeatin riboside. The cosmetic for regenerating a skin structure according to claim 1.