JPS6251605A - Dermal drug for external use - Google Patents

Abstract

PURPOSE:A dermal drug for external use, obtained by incorporating dextran sulfate or a salt thereof and allantoin and a derivative thereof with other components and capable of preventing and improving the skin roughening and further preventing loosening off the skin and disappearance of gloss, etc., and preventing aging. CONSTITUTION:A dermal drug for external use obtained by incorporating (A) destran sulfate expressed by formula I (R is SO3Na or H), preferably having 0.02-0.05, particularly 0.02-0.03 intrinsic viscosity using 1M saline solution at 25 deg.C and 2-20wt%, particularly 16-19wt% sulfur content or a salt thereof, e.g. alkali salt of salt of an organic amine such as triethylamine, and (B) allantoin expressed by formula II and a derivative thereof, e.g. dihydroxyaluminum allantionate, with other components. The amounts of the components based on the total weight of the dermal drug for external use are respectively as follows; 0.005-2wt% particularly 0.05-0.5wt% components (A) and (B).

Description

[Detailed Description of the Invention] [Industrial Application Field 1] The present invention is a skin preparation for external use, and more specifically, it is highly effective in preventing skin roughness, improving skin roughness, and preventing aging by preventing skin sagging and loss of luster. Regarding skin external preparations.

[Prior Art] Various medicinal agents are blended into external preparations for the skin. - The effect of preventing rough skin is one of the medicinal effects, and a medicinal agent that has the effect of preventing and improving skin roughness is long awaited.

Conventionally, allantoin or allantoin derivatives have been used to improve rough skin, but their effects have not yet been sufficient to meet expectations.

[Problems to be Solved by the Invention] The present inventors have wondered if there is a way to enhance the anti-aging effect of allantoin or allantoin derivatives by preventing and improving skin roughness, as well as preventing skin sagging and loss of luster. As a result of extensive research, the present invention was completed by discovering that this object can be achieved by combining allantoin or an allantoin derivative with dextran sulfate or a salt thereof.

[Means for Solving the Problems] That is, the present invention provides an external skin preparation characterized by blending dextran sulfate or a salt thereof with one or more of allantoin and allantoin derivatives. It is.

Hereinafter, the configuration of the present invention will be explained in detail.

The dextran sulfate used in the present invention has the structure shown below.

R: SokoN Kame or 11 The dextran sulfate ester used in the present invention may be produced according to a conventional method, but Ibara is an example. .

That is, simisaccharide is fermented to produce dextran, which is then hydrolyzed to obtain low-molecular-weight dextran. The raw material is sulfuric acid esterified to obtain dextran sulfate, treated with caustic soda and purified to obtain dextran sodium sulfate.

The dextran sulfate used in the present invention is 1M
AI limiting viscosity at 25℃ in saline solution is 0゜02~0
．． 05 with a sulfur content of 2-20% by weight is suitable for practical use, and in particular, one with an intrinsic viscosity of 0.02-0.03 and a sulfur content of 18-19% by weight is excellent. Examples of the salts include alkali salts such as sodium, potassium, and ammonium salts, and salts of organic bases such as triethanolamine.

The amount of dextran sulfate or its salt in the present invention is 0.005 to 2% by weight, preferably 0.01 to 1% by weight, more preferably 0.005 to 2% by weight, preferably 0.01 to 1% by weight, based on the total amount of the skin external preparation.
．． 05 to 0.5% by weight. If the content is less than o, oos weight percent, the effect will not be exhibited, and if it exceeds 2 weight percent, it is unfavorable in the manufacturing process of the product.

Allantoin used in the present invention has the structure shown below.

Furthermore, examples of allantoin derivatives include dihydroxyaluminum allantoinate, chlorohydroxyaluminum allantoinate, and the like.

The amount of allantoin or its derivative in the present invention is 0.005 to 2% by weight, preferably 0.01 to 1% by weight, more preferably 0.05 to 1% by weight, based on the total amount of the skin external preparation.
It is 0.5% by weight. If the amount is less than o, oos weight percent, the effect cannot be sufficiently exhibited.

In addition to the above-mentioned essential ingredients, the external skin preparation of the present invention may optionally contain various ingredients commonly used in cosmetics, pharmaceuticals, etc., i.e., aqueous ingredients, to the extent that the effects of the present invention are not impaired.
Powder components, oils, surfactants, humectants, thickeners, preservatives, antioxidants, fragrances, colorants, ultraviolet absorbers, drugs, etc. can be blended. Further, the dosage form of the skin external preparation of the present invention is arbitrary, and may be, for example, a solubilized skin lotion type, an emulsified type such as a milky lotion or a cream, or a dosage form such as an ointment, a dispersion liquid, or a powder product.

[Example] Next, the present invention will be roughly described in detail with reference to Examples. Note that the present invention is not limited to this. The blending amount is by weight.

Wound Healing Test Eight-week-old male Wester rats were divided into groups of five, and after nine shaves, they were subjected to the test. Rats were anesthetized with Nembutal. Approximately 2 cm of dorsal skin was incised along the midline, and the incision was immediately sutured with Mitsuhel sutures, and a 0.1 ml sample was placed.
was applied once a day for 2 weeks. The suture needle was removed after 3-4 days. Two weeks later.

The rat was sacrificed and a 2 cm wide strip of skin was cut around the incision. Tensilon TM-4 for tension measurement
(The cutting tension of the skin section was measured using Toyo Keikki Co., Ltd.).

Note that physiological saline was used as a control, and in Examples and Comparative Examples, this physiological saline was mixed with allantoin and sodium dextran sulfate in the amounts shown in the table below.

The results are shown in Table 1.

(Margins below) Table 1 From the results in Table 1, in the case of the product of the present invention combined with sodium dextran sulfate and allantoin, there was a tendency for the tension to increase compared to the comparative amount of each applied alone, and it had a remarkable healing promoting effect. was recognized.

Furthermore, in addition to the above animal test, in a human panel, this combined system of dextran sulfate sodium and allantoin showed the same effect as the results of this animal test.

Example 1 Cream A, stearic acid 10.0 Stearyl alcohol 4.0 Butyl stearate 8.0 Stearic acid monoglycerin ester 2.0 Fragrance 0.4 Preservative
Appropriate amount B, propylene glycol 10.0 dextran sodium sulfate 2.0 allantoin
0.5 Glycerin 4.0 Potassium hydroxide 0.4 Trisodium edetate 0.05 Purified water
The remaining oil phase part A and water phase part B are each heated to 70°C to completely dissolve them. Add phase A to phase B and emulsify with an emulsifier. The emulsion was cooled using a heat exchanger to obtain cream.

Comparative Example 1 Comparative Example 1 was obtained in the same manner as in Example 1 except that dextran sodium sulfate was removed.

Comparative Example 2 All Example 1 except that allantoin was removed from Example 1.
Comparative Example 2 was obtained in the same manner.

Skin roughness prevention and skin improvement effect test A replica of the skin surface morphology of a healthy female person (face) was taken using a replica method using myristic resin and examined under a microscope (1
Observation was made at 7x magnification. In other words, rough skin evaluation 1 based on the criteria shown in Table 1 based on the condition of the skin pattern and the peeling condition of the stratum corneum.
．． The creams obtained in Example 1, Comparative Example 1, and Comparative Example 2 were applied twice a day to the left and right half of the face of 30 people who were judged to have skin irritation of 2 (rough skin panel). Two weeks later, a replica was taken again and the condition of the skin was observed and evaluated according to the criteria in Table 2.

(Margin below) Table 2 The results are shown in Table 3.

(Margins below) Table 3 From these results, it was found that the facial areas treated with the cream containing allantoin and dextran sodium sulfate had a significant effect on preventing and improving rough skin compared to facial areas using other creams. .

(Left below) Example 2 Cream A, Cetanol 4.0 Vaseline 7.0 Isopropyl myristate 8.0 Squalane 15.0 Stearic acid monoglycerol ester 2.2 POE (20 mol) Sorbitan monostearate 2.8 Fragrance 0 .3 Antioxidants Appropriate amount of preservatives
Appropriate amount B, glycerin
10. O dipropylene glycol
5.0 Dextran Sodium Sulfate 0.02
Allantoin 2.0 Disodium edetate 0.01 Purified water
A cream was obtained according to the rest of Example 1.

Example 3 Emulsion A, squalane 5.0 oleyl oleate 3.0 petrolatum 2.0 sorbitan sesquioleate 0.8 polyoxyethylene (20 mol) oleyl ether 1.2 fragrance 0.3 preservative
Appropriate amount B, 1.3 Butylene glycol 5.0 Dextran sulfate potassium 1.5 Allantoin
0.3 ethanol 3.
0 Ruboxyvinylborrimer-0.2 Potassium hydroxide 0.1 Sodium hexametaphosphate 0.05 Purified water
A milky lotion was obtained according to the rest of Example 1.

Example 4 Foundation A, Setanol 3.5 Deodorized lanolin 4.0 Jojoba oil
5.0 Vaseline
2.0 squalane
6.0 Stearic acid monoglycerin ester 2.5 Stearyl glycyrrhetinate 0.01 POE
(60 mol) Hydrogenated castor oil 1.5P
OE (20 mon) Cetyl ether 1.
0 preservatives, appropriate amount of fragrance
0.3B, propylene glycol 10.0 Sodium dextran sulfate 1.0 Dihydroxyaluminum allantoinate 0.1 Mixed powder 12.0 Trisodium edetate 0.2 Purified water
A foundation was obtained according to the rest of Example 1.

Example 5 Lotion A, ethanol 5.0PO
E (20 mol) Oleyl alcohol ether 2.0 2-ethylhexyl-P-dimethylaminobenzoate 0.18 Fragrance 0.05B, 1
．． 3 Butylene glycol 10.0 Sodium dextran sulfate 0.02 Allantoin
0.005 glycerin
5.0 ascorbic acid
0.4 Purified water The remaining alcohol phase of A was added to the aqueous phase of B and solubilized to obtain a lotion.

Example 6 Ointment Dextran sodium sulfate 1.0 Allantoin 0.5 Stearyl alcohol 18.0 Mokuro
20.0 POE (10 mol) Monooleic acid ester 0.25 Glycerin monostearic acid ester 0.25 Vaseline
40.0 Purified water
Residue (manufacturing method) Sodium dextran sulfate and allantoin were dissolved in purified water and kept at 70°C (water phase), and other components were mixed and dissolved at 70°C (oil phase). Next, the oil phase was added to the aqueous phase, uniformly emulsified using a homomixer, and then cooled to obtain an ointment.

[Effects of the Invention] By incorporating dextran sulfate or its salt, the skin external preparation of the present invention has the effect of preventing and improving skin roughness, which allantoin or allantoin derivatives have, and prevents skin sagging, loss of luster, etc., and prevents aging. It has the advantage of significantly increasing the preventive effect without causing side effects.

Claims (1)

[Claims] 1. A skin preparation for external use, comprising a combination of dextran sulfate or a salt thereof and one or more of allantoin and allantoin derivatives.