JPS5934168B2 - New aloin or aloe-emodin compound and cosmetics containing it - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is an emodin that is free of sugar due to the structure of Alone or Alone.

The present invention relates to a novel compound obtained by ester bonding stearic acid to aloe emodin, and a cosmetic containing the compound. More specifically, barbal0in C21H2209-1 is an anthraquinone substance contained in plants (aloe, rhubarb, etc.).
01D-glucopyranosyl-aloe-9
- extracting a sugar-free substance (emodin) from anthrone or the aloin structure coexisting with alone in the plant, and bonding it with an organic acid ester to obtain a new compound; It enables oil solubilization, making it even more advantageous to incorporate into cosmetics.

Regarding the application to cosmetics such as Alone, the present inventors have already published Japanese Patent Publication No. 5345376,
No. 2-44375, etc., and it was discovered that Alone has a tyrosinase activity inhibiting effect, suppresses the production of melanin pigment, and is expected to have a whitening effect.

Alone also states that it is useful as a stabilizer for vitamin C (ascorbic acid) in aqueous solutions. However, the drawback is that when looking at the conventional application (formulation) of Alone to cosmetics, both Alone and its Emodin contain liquid fats and oils (olive oil, apricot oil, almond oil, and various other types) that are mainly used in cosmetics. It was hardly soluble in mineral oils such as vegetable oil, liquid paraffin, vaseline, and ceresin, and esters such as isopropyl myristate, myristyl myristate, and isopropyl palmitate. Therefore, when applying (compounding) to cosmetics, mainly water or lower alcohols such as methyl, ethyl, and propyl alcohol, and polyols such as polyethylene glycol, propylene glycol, and butylene glycol are partially used. Therefore, its use has been limited due to the formulation of cosmetics. Therefore, the present inventors have continued intensive research into the oil-solubilization of Alone and its emodin, which has an inhibitory effect on melanin production, and have found that by obtaining an ester of Alone or its emodin with an organic acid, the oil-solubilization effect can be improved. It was a success. According to the production method according to the present invention, an ester with stearic acid can be produced by reacting alone or aloe emodin with stearic acid chloride. The formula for this is as follows. [1] An example from Alone.

In the formula, R represents a carboxylic acid residue of stearic acid, X represents chlorine or bromine, and B represents a basic acid binding agent. The above-mentioned esterification method of alone or aloe emodin in the present invention includes, in other substances,
This may be done in accordance with a known method, but the operating method is as follows.

"Production method example" 1 mole of Alone or Aloe emodin extracted and purified from aloe is dissolved in 5 to 10 times the amount (weight) of N-N-disubstituted amide, and then 1.5 to 5.0 times the amount (weight) of the basic acid binder is added. 2.2 to 4.0 moles of stearic acid chloride was added dropwise at a temperature of 50 to 70°C with stirring over a period of about 1 hour, and after the dropwise addition was completed, the mixture was heated at the same temperature Stir for several more hours.

The solvent as well as any remaining basic acid binder is then removed,
Add an appropriate amount of water to the residue to precipitate and disperse the target product in the water.
After dispersing, filter and wash with water several times.
Once again dispersed in water, an organic solvent in which the target substance is soluble is added, extracted, and purified by a method such as recrystallization.
The novel ester compound of alone or aloe emodin obtained by the method described above is a light yellowish brown crystalline substance that is sparingly soluble or insoluble in water but soluble in organic solvents.

Alone and Aloe Emodin have the feature that they dissolve well in various vegetable oils, mineral oils, and various fatty acid esters, whereas Alone and Aloe Emodin do not dissolve at all, and also dissolve in higher fatty acid esters such as stearic acid and palmitic acid. [Confirmation of physical properties] On the other hand, according to the above manufacturing method,
For example, when considering an aloin-stearate compound, if you compare the confirmation test of that substance with alone,
When reacting with a bromine test solution, which is generally used in confirmation tests for Alone, a pale yellow precipitate is produced, and when reacting with a methanolic ferric chloride test solution, it is colored red, maintaining the original characteristics of Alone. I found out that there was.

In addition, when looking at the behavior on thin layer chromatography, there are differences in Rf values, and in general, esters have higher Rf values.
It was found that the value was shown (Fig. 1). Next, looking at the ultraviolet absorption spectrum (alcohol solution), its lambda maximum shows 269, 296, and 359 nm, and its lambda minimum shows 275 and 315 nm.

In other words, in the case of aloin, it shows peaks around 296 and 359, and its characteristic is that the peak at 359 nm is higher than that at 296 nm, whereas in the case of aloin-stearate compound, the peak at 296 nm is higher than that at 296 nm. The feature is that the peak is higher than the 359 nm peak. (Figure 2). On the other hand, in terms of stability, it was found that the browning phenomenon of the ester compound was considerably suppressed under sunlight irradiation and heating conditions, compared to Alone and Aloe-Emodin.

In other words, when Alone itself was isolated from a plant and exposed for a long period of time to the air, sunlight, or heating conditions, browning progressed, and one of the factors was
It is thought that browning progresses because side chains such as -0H and -CH2OH, which are chromophores in the structure of Alone and Aloe-Emodin, act as coloring factors when affected by ultraviolet rays and heat. In the fatty acid ester compound of alone or aloe-emodin obtained by the present invention, such coloring tendency is significantly improved and its stability is improved. These benefits are something that could never be achieved with conventional Alone or Aloe Emodin, and even when formulated into cosmetics and pharmaceuticals, their browning can be improved. In addition, as understood from the chemical structure, emulsification and dispersion states of cosmetics and the like are also advantageous because they meet the conditions as surfactants.

The following (Table 1) shows the solubility results of the ester compound according to the present invention as well as Alone and Aloe Emodin.

Moreover, the manufacturing method itself does not need to be particularly limited, as it is possible to use all conventionally known ester manufacturing methods, but when used in cosmetics, Alone or aloe emodin, which is the starting material, does not necessarily have to be a pure product.

For example, when isolating and extracting alone from the aloe plant, the crude product can be used as it is obtained as a complex of alone and aloe emodin. That is, since both Alone and Aloe-Emodin have a tyrosinase activity suppressing effect and suppress the production of melanin pigment, they can be used as starting materials even if the two substances are not completely separated and purified. However, since Alone has a more beautiful characteristic lemon color than Aloe Emodin, it seems more advantageous to use isolated Alone in cosmetics.
Regarding the inhibitory effect on tyrosinase activity, vitamin C (L
-Ascorbic acid), alone, aloe emodin, etc., its action is strong and its thermal stability is also excellent (Table 2).

Pour 20 ml of solution A into a shear dish with a diameter of 8 (1-J mo V!), cool and solidify it, pour 0.5% tyrosinase solution over it, and leave it in a constant temperature bath at 37 °C for a predetermined time. The degree of blackening on the agar surface was observed, and the presence or absence of the inhibitory effect on tyrosinase activity was determined.

Next, regarding the ester compound of alone or aloe emodin according to the present invention, if we show the formulation (compounding) percentage in cosmetics, it usually shows a sufficient tyrosinase activity inhibiting effect at 1.0% or less. , is expected to have a skin whitening effect.

However, in the case of pharmaceutical topical preparations, a content of about 3 to 5% may be considered. Referring to reference formulation examples, as shown below, it can be formulated into various dosage forms and does not cause precipitation or browning over a long period of time. Regarding acute toxicity according to the present invention, the ester compound of Alone and the ester compound of Aloe-emodin were administered by subcutaneous injection (S) to female Dd mice.
．． C. ) and both were over 4000m9/Kg.

Furthermore, no absorption in the body was observed after subcutaneous injection. Furthermore, primary eye mucosal irritation was tested using domestic rabbits. Immediately after administration, flushing was observed in the conjunctiva, but the irritation index values determined that the cornea, erythema, and conjunctiva were all zero. For administration, Sample 17 was poured into 10 ml of olive oil and then administered. As described above, it was found that the organic acid ester compound of Alone or Aloe-emodin itself according to the present invention has much lower acute toxicity and is highly safe than Alone or Aloe-emodin.

Moreover, such a novel compound has never been seen before, and is also useful.

[Brief explanation of the drawing]

FIG. 1 shows the Rf values of the aloin-stearate compound, the aloe-emodine-stearate compound, and the alone and aloe-emodine compounds. Figure 2 shows an aloin-stearate compound and
This shows the ultraviolet absorption spectrum of Alone and Aloe Emodin. Development time - 90 minutes A is an aloin-stearate compound, B is an alone, C is an aloe-emodin, and D is an aloe-emodin-stearate compound.

Claims (1)

[Scope of Claims] 1 A novel iron compound represented by the general formula ▲A mathematical formula, a chemical formula, a table, etc.▼[1] (in the formula, R represents a stearic acid residue) [1], or a general Formulas include ▲mathematical formulas, chemical formulas, tables, etc.▼[2] (In the formula, R represents a stearic acid residue)
A novel aloe-emodin compound represented by [2]. 2 The general formula is ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [1] (In the formula, R represents a stearic acid residue) [1] The new iron compound, or the general formula is ▲ Mathematical formula, There are chemical formulas, tables, etc. ▼ [2] (In the formula, R represents a stearic acid residue)
A cosmetic containing the novel aloe-emodin compound shown in [2].