JPH1179930A - Ascorbic acid derivative composition for skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a composition capable of making vitamin C effectively act, by including an ascorbic acid ester and an ether a phospholipid and a polyalkylene glycol diisocyanate copolymer. SOLUTION: This composition comprises (A) 0.1-10 wt.% of at least one of an ascorbic acid ester (an inorganic acid ester, a 2-22C organic acid ester, etc., such as L-ascorbic acid phosphoric ester magnesium salt, etc.), and ether (an ether of a 2-12C alcohol and a saccharide) and (B) 0.01-80 wt.% of at least one of a phospholipid (a phospholipid derived from a plant such as soybean or from egg yolk) and a polyalkylene glycol diisocyanate copolymer [e.g. a polyalkylene glycol methylene diisocyanate cyclohexane copolymer of formula I or formula II (preferably (m) is 1-8 and (n) is 4-55, more preferably (m) is 1-4 and (n) is 8-12 and 50-55)].

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel skin ascorbic acid derivative composition, and more particularly, to acne, rosacea,
The present invention relates to a novel ascorbic acid derivative composition which is effective for treating, improving or preventing seborrheic dermatitis. For example, the present invention is applicable to cosmetics such as creams, emulsions, lotions, and packs, and pharmaceuticals such as ointments for acne, rosacea, and seborrheic dermatitis.

[0002]

2. Description of the Related Art Acne, rosacea, and seborrheic dermatitis are active oxygen diseases caused by excessive secretion of sebum. Sebum secretion is promoted from the sebaceous glands by stimulation of androgen stimulation of sebaceous glands and stimulation by various fatty acids. Also, coupled with the narrowing of the follicles by keratinization of the follicular epithelium,
Secreted sebum is prevented from being discharged to the skin surface, and sebum is stored in the hair follicle.

[0003] Acne bacteria are lipophilic bacteria and grow in the stored cortex. As a result, hydrolysis occurs by lipase, free fatty acids and glycerin are produced, inflammation,
Pustular formation occurs.

Until now, as a countermeasure against acne, excessive sebum has been removed by washing the face, and the growth of acne bacteria has been suppressed by a fungicide to prevent suppuration.
The effect was not enough.

[0005]

The actions of vitamin C include (1) eliminating active oxygen; (2) closing pores by antiseborrheic action; (3) reducing acne bacteria by bactericidal action; and (4) It is considered that vascular tissue is strengthened by promoting the synthesis of collagen.

Therefore, it has been used for the above-mentioned diseases and the like in order to utilize the action of the above-mentioned vitamin C. However, conventionally used vitamin C has a low sustained action and low transdermal absorbability, and cannot exert its effect sufficiently.

[0007] If the action of vitamin C can be effectively exerted, secretion from sebaceous glands can be suppressed by preventing oxidation of secreted lipids and reducing irritation of hair follicles by acid. . This suppresses the growth of acne bacteria, and reduces the amount of fatty acids produced by hydrolysis with lipase derived from acne bacteria. Therefore, development of a drug that has its action continuously and enhances transdermal absorption to effectively act on vitamin C is expected.

[0008]

Means for Solving the Problems In view of the above problems, the present inventors have made intensive studies and have found that at least one of esters and ethers of ascorbic acid, a phospholipid and a polyalkylene glycol-diisocyanate copolymer. ,
For example, the present inventors have found that an ascorbic acid derivative composition containing at least one polyalkylene glycol methylene diisocyanate cyclohexane polymer is extremely excellent in terms of the above-mentioned effects of persistence and percutaneous absorption, thereby completing the present invention. Reached. In particular, by absorbing the ascorbic acid derivative of the present invention into the dermis layer, the antioxidant effect and the effect of suppressing the generation of lipid peroxides and fatty acids are effectively exhibited. This has also made it possible to prevent irritation, prevent skin inflammation, and more effectively prevent pustular formation.

That is, the present invention contains at least one kind of ester and ether of ascorbic acid, and at least one kind of polyalkylene glycol-diisocyanate copolymer such as phospholipid and polyalkylene glycol methylene diisocyanate cyclohexane polymer. It is an ascorbic acid derivative composition for skin.

[0010]

Embodiments of the present invention will be described.
Examples of the ester of ascorbic acid of the present invention include esters of inorganic acids such as sulfuric acid, phosphoric acid and carbonic acid, and esters of organic acids having 2 to 22 carbon atoms such as palmitic acid and stearic acid. Examples of the ether of ascorbic acid include an ether with an alcohol having 2 to 12 carbon atoms such as ethyl alcohol, isopropyl alcohol, and octyl alcohol, and an ether with a sugar such as sucrose, fructose, lactose, and trehalose. In the present specification, these ester and ether forms include not only a free form but also a salt form of sodium, potassium, magnesium, calcium, aluminum and the like.

Examples of specific compounds include magnesium L-ascorbic acid phosphate, sodium L-ascorbic acid phosphate, potassium L-ascorbic acid potassium salt, calcium L-ascorbic acid phosphate, L-ascorbic acid sulfate sodium salt, L-ascorbic acid potassium salt potassium, L-ascorbic acid calcium sulfate salt, L-ascorbic acid palmitate, L
-Ascorbic acid stearic acid ester, L-ascorbic acid isopropyl ether and the like.

The content of the ascorbic acid derivative varies depending on the dosage form, severity, etc. of cosmetics or pharmaceuticals, but usually 0.1 to 10% (weight) is preferably used as the total amount of ascorbic acid derivative used. , More preferably in the range of 0.5 to 7% (weight).

The phospholipids used in the present invention may be included in the definition of phospholipids, and include those obtained by hydrogenation, enzymatic decomposition and hydrolysis. Phospholipids and derivatives thereof, including phospholipids obtained from plants such as soybeans or egg yolk or hydrogenated phospholipids obtained by hydrogenating them, enzymatically decomposed lysophospholipids, hydroxylated phospholipids, etc. are also included.
Particularly preferred are phospholipids derived from plants such as soybean or egg yolk, and phospholipids obtained by hydrogenating them. Further, the polyalkylene glycol-diisocyanate copolymer used in the present invention may be any one obtained by forming a polymer with a polyalkylene glycol and a diisocyanate.For example, a polyalkylene glycol methylene diisocyanate cyclohexane copolymer is a polyalkylene glycol. And a copolymer of methylene diisocyanate cyclohexane with the following formula:

[0014]

Embedded image

## EQU1 ## M and n in the formula are respectively preferably m 1 to 8, n 4 to 55, and more preferably m
Is 1 to 4, and n is 8 to 12 or 50 to 55.

In the present invention, the phospholipid and / or the polyalkylene glycol methylene diisocyanate cyclohexane polymer is blended in order to enhance percutaneous absorbability, and one of the phospholipid and the polyalkylene glycol methylene diisocyanate cyclohexane polymer is used. Alternatively, both are used, but the total content thereof, that is, one of the amounts used when using one of the phospholipid or the polyalkylene glycol methylene diisocyanate cyclohexane polymer, and the total content of both when using both, is as described above. As in the case of the ascorbic acid derivative, it depends on the form, severity, etc. of cosmetics and pharmaceuticals. Usually, preferably 0.01 to 80%, more preferably 0.1 to 20%.
%.

The composition of the present invention can be used for cosmetics and pharmaceuticals, but the dosage form is not particularly limited. It can be applied in a general form of cosmetics and pharmaceuticals such as emulsified creams or emulsions, lotions, packs, and powders.

[0018]

In the present invention, unstable vitamin C can be chemically stabilized by converting vitamin C into an ester or ether form of ascorbic acid, and is used in various cosmetic preparations or dermatological preparations. In this case, it is stably present as vitamin C and is a preparation excellent in the persistence of the effect, so that it can be easily used in cosmetics and pharmaceuticals. Furthermore,
When the phospholipid and / or polyalkylene glycol-diisocyanate copolymer is applied to the skin as a pharmaceutical such as a cosmetic or an ointment, the ascorbic acid derivative of the present invention such as magnesium L-ascorbic acid phosphate quickly penetrates into the skin. Since it diffuses, it is absorbed into the dermis layer and effectively exerts an antioxidant effect and an effect of suppressing the generation of lipid peroxides and fatty acids.

The secretion from the sebaceous glands is suppressed by preventing oxidation of secreted lipids and reducing irritation of hair follicles by acids. This suppresses the growth of acne bacteria and reduces the amount of fatty acids produced when hydrolyzed by lipase derived from acne bacteria. The antioxidant effect of the ascorbic acid derivative of the present invention suppresses the generation of lipid peroxides and fatty acids, thereby preventing skin inflammation and preventing the formation of pustules. As a result, the function of the sebaceous glands is maintained normally, and secretion from the sebaceous glands is suppressed. When the amount of sebum secreted is reduced, the growth of acne bacteria is suppressed, the sebum is less likely to be decomposed by lipase due to this, and the production of stimulating components such as lipid peroxide and fatty acids is suppressed, and the skin is maintained normally. Dripping.

As described above, the action of suppressing excessive secretion of sebum makes it possible to treat, improve, or prevent the fundamental onset of acne, rosacea, and seborrheic dermatitis.

[0021]

EXAMPLES Next, the formulation examples of the ascorbic acid derivative composition for skin of the present invention and the effects obtained thereby will be specifically described.

(Example 1) L-ascorbic acid phosphate magnesium salt (NIKKOL VC-PMG)
Was applied twice daily to 20 female patients aged 18 to 24 years.

[Prescription of Cream] A cream was prepared according to a conventional method based on the following composition. % (Weight) • Polyethylene glycol (PEG 55) monostearate (NIKKOL MYS-55) 2.00 • Self-emulsifying glyceryl monostearate (NIKKOL MGS-DEX) 5.00 • Cetyl alcohol (NIKKOL Cetanol) 4.00 -Squalane (NIKKOL squalane) 6.00-Glyceryl trioctanoate (NIKKOL S-308) 6.00-1,3 butylene glycol 7.00-L-ascorbic acid phosphate magnesium salt (NIKKOL VC-PMG) 5.00・ Hydrogenated soybean phospholipid (NIKKOL resinol) 1.50 ・ Copolymer of polyalkylene glycol and methylene diisocyanatecyclohexane (polyolpreppolymer-2) * 4.00 ・ Purified water 00 *: Penedamu Co., Ltd.

[Judgment Method] Judgment was carried out on the facial pore-matched papules, pore-matched pustules, erythema, hair follicle opening degree, hot flashes,
The flushing is judged based on the patient's subjective findings and the objective findings by photographs, and the effectiveness is markedly significant, effective, slightly effective, ineffective and worse 5
The evaluation was divided into stages. [result]

[0025]

[Table 1]

The percentage showing "effective" was 90%, indicating a very high effect. In the above examples, L-ascorbic acid phosphate magnesium was replaced by L-ascorbic acid magnesium phosphate.
-Sodium ascorbic acid sulfate (NIKKO
Example 1 was repeated without any changes except using LVC-SS). Similarly, when a cream was prepared, applied to a patient, and evaluated in the same manner, almost the same preferable results were obtained.

(Comparative Example) In the above-mentioned Example 1, the cream was prepared without containing only hydrogenated soybean phospholipid and polyalkylene glycol methylene diisocyanate cyclohexane polymer, and purified water was added by that amount to prepare a cream.
The same evaluation was performed using patients, and an unfavorable result of 10 out of 20 patients combined with ineffectiveness was obtained.

(Example 2) A lotion containing magnesium L-ascorbic acid phosphate was used at an age of 16 to 2 years.
It was applied twice daily to 22 4-year-old female patients.

[Formulation of lotion] A lotion was prepared by a conventional method based on the following composition. % (Weight)-Magnesium L-ascorbic acid phosphate ester (NIKKOL VC-P MG) 7.00-Sodium citrate 0.10-Citric acid 0.05-Hydrogenated soybean phospholipid 0.20-1,3 Butylene glycol 3.00 ・ 100 with purified water

[Determination Method] The same determination method as in Example 1 was used.

[Results]

[0032]

[Table 2]

The percentage showing "effective" was 95%, indicating a very high effect.

Example 3 A pack containing magnesium L-ascorbic acid phosphate was packed once a day for 20 minutes in 16 patients aged 20 to 24 years.

[Pack Formulation] A pack was prepared according to a conventional method based on the following composition. % (Weight) ・ Polyvinyl alcohol * 13.00 ・ L-ascorbic acid phosphate magnesium salt (NIKKOL VC-PMG) 3.00 ・ Polyalkylene glycol, methylene disiocyanate cyclohexane copolymer (Polyolprepopolymer-2) 00 • 1,3-butylene glycol 3.00 • Ethanol 5.00 • Purified water 100 *: Gohsenol EG40 (Nippon Synthetic Chemical Industry)

[Determination Method] The same determination method as in Example 1 was used.

[Results]

[0038]

[Table 3]

The ratio showing "effective" was 95%, indicating a very high effect. Note that the pack of Example 3 was repeated with no change except that L-ascorbic acid palmitic ester was used instead of the magnesium L-ascorbic acid phosphate.
Similarly, when a pack was prepared and packed in a patient and evaluated in the same manner, almost the same preferable results were obtained.

(Example 4) Powder cosmetics containing magnesium L-ascorbic acid phosphoric acid ester were used for ages 18 to 2
It was applied twice daily to 18 7 year old patients. The application method was such that 100 mg of a predetermined powder cosmetic was dispersed and dissolved in 1 ml of water and applied to the face. (At the time of use, L-ascorbic acid phosphate magnesium salt was adjusted to 5% and used.)

[Prescription of Powder Cosmetics of Example 4] L-ascorbic acid phosphate magnesium salt% (weight) (NIKKOL VC-PMG): 50.00 Dextran (Dextran 40): 15.00 Maltose: 20.00 ・ Hydrogenated soybean phospholipid (NIKKOL Resinol S-10E): 3.00 ・ Lactose: 12.00

[Determination Method] The same determination method as in Example 1 was used.

[Results]

[0044]

[Table 4]

The ratio showing "effective" was 94%, indicating a very high effect.

[0046]

The effect of vitamin C is sustained by incorporating the ascorbic acid derivative of the present invention and a phospholipid and / or a polyalkylene glycol-diisocyanate copolymer such as a polyalkylene glycol methylene diisocyanate cyclohexane polymer. In addition, the anti-oxidant effect of vitamin C and the effect of suppressing the generation of lipid peroxides and fatty acids can be exhibited more effectively by increasing the transdermal absorbability. As a result, it is effective in treating, improving and preventing diseases such as acne, rosacea, and seborrheic dermatitis.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 7/00 A61K 7/00 Y 7/48 7/48 31/375 ADA 31/375 ADA 47/14 47/14 E 47 / 24 47/24 E 47/30 47/30 E

Claims (6)

[Claims] 1. A skin ascorbic acid derivative composition comprising at least one of esters and ethers of ascorbic acid and at least one of a phospholipid and a polyalkylene glycol-diisocyanate copolymer. The esters and ethers may be in the form of a salt. 2. The total content of the ester and / or ether of ascorbic acid is 0.1% to 10% (by weight), and the total content of the phospholipid and / or the polyalkylene glycol-diisocyanate copolymer is 0.01%. The composition of claim 1 wherein the composition is about 80% (by weight). 3. The ester of ascorbic acid is any one or a combination of two or more of L-ascorbic acid magnesium phosphate, L-ascorbic acid sulfate sodium salt and L-ascorbic acid fatty acid ester, The composition according to claim 1, wherein the ether of ascorbic acid is one or a combination of two or more of L-ascorbic acid sugar ether and L-ascorbic acid alkyl ether. 4. The method according to claim 1, wherein the phospholipid is at least one of plant-derived phospholipids, egg yolk-derived phospholipids, hydrogenated products thereof, lysophospholipids which are enzymatically degraded phospholipids, and hydroxylated phospholipids into which hydroxyl groups have been introduced. The composition according to claim 1, wherein the polyalkylene glycol-diisocyanate copolymer is a polyalkylene glycol methylene diisocyanate cyclohexane polymer represented by the following formula. Embedded image [Wherein, m represents a natural number of 1 to 8, and n represents a natural number of 4 to 55.] ] 5. The composition according to claim 1, which is a cosmetic or an external preparation for skin. 6. The composition according to claim 1, which is used for treating, improving and preventing acne, rosacea and seborrheic dermatitis.