JPS6245201B2 - - Google Patents

Description

[Detailed description of the invention]

This invention relates to an external skin preparation that aims to utilize nicotinic acid derivatives, which are highly safe, have excellent surfactant functions, and have mild effects on the skin, as a surfactant, a bacteriostatic agent, or both. be. Nicotinic acid is a vitamin also known as niacin.
_B3 constitutes the coenzyme nicotinamide adenine dinucleotide (NAD ⁺ ) and its phosphate ester (NADP ⁺ ), which are important oxidoreductase enzymes in maintaining life phenomena in living organisms. Also, pellagra treatment,
It is also well known to be effective in treating chronic alcoholism, chilblains, and glossitis. On the other hand, alkylpyridinium salts, alkyltrimethylammonium salts, alkyldimethylbenzylammonium salts, etc. are cationic surfactants that are widely used in a wide range of fields such as rinse agents, disinfectants, softeners, and antistatic agents. When left on the skin, it causes strong irritation, which is a side effect characteristic of surfactants, so it is not preferable to use it for anything other than cosmetics, such as hair conditioners and treatments. The present invention has been made in view of the current situation, and provides an external skin preparation characterized by containing a nicotinic acid derivative represented by the following general formula [A] or [B]. . Record (In the formula, R ₁ represents a straight chain or branched alkyl group having 8 to 30 carbon atoms, R ₂ represents a straight chain or branched alkyl group having 1 to 30 carbon atoms and a phenyl group, and X represents a halogen group.) , the details of this invention will be described. First, the 1-alkyl-3-carbamide pyridinium salt represented by the general formula [A] and the 1-alkyl-3-alkylcarbamide pyridinium salt represented by the general formula [B] that are applied to this invention are This was discovered as a result of a study focusing on the physiological effects and efficacy of nicotinamide.
It is a NAD ⁺ model compound and is clearly classified as a natural surfactant. When such compounds are present in the interfacial region, oily components can be emulsified very easily.
This is probably due to the formation of charge transfer complexes in a broad sense between the pyridinium skeleton and other formulation components, but the micelles and emulsions formed are extremely stable and have surfactant and bacteriostatic functions. It can be applied to external skin preparations such as lotions, emulsions, creams, and hair conditioners, which have hypoallergenic properties that cannot be obtained with conventional cationic surfactants. There are many methods for synthesizing such nicotinic acid derivatives, but for example, for [A], a method in which nicotinic acid amide is reacted with a desired alkyl halide in a solvent such as ethanol or dimethylformamide is advantageous; For [B], nicotinic acid is reacted with an excess chlorinating agent such as thionyl chloride to form nicotinic acid chloride, and this is reacted with an alkylamine in a solvent such as benzene in the presence of a base such as triethylamine to form 3- An advantageous method is to generate an alkylcarbamide pyridine and then react it with a desired alkyl halide in a solvent such as ethanol. Specific examples of these methods are as follows. Synthesis example of [A]: 1.22 g (0.01 mol) of nicotinamide was dissolved in 15 ml of dimethylformamide, 2.89 g (0.01 mol) of stearyl chloride was added, the mixture was reacted under reflux for 2 hours, and then allowed to cool to room temperature. The produced white crystals were filtered with suction and washed with ether to obtain 2.5 g of 1-stearyl-3-carbamidopyridinium chloride. On the other hand, the dimethylformamide solution of the filtrate was concentrated to several ml, heated once, and left overnight under ice cooling to obtain 1.2 g of the same product. The overall yield in this synthesis example was 90%. Synthesis example of [B]: 1.85 g (0.015 mol) of nicotinic acid and thionyl chloride
10 ml was added and stirred at 70-80°C for 1 hour. After the reaction, thionyl chloride was removed by distillation, and the nicotinic acid chloride crystals were sealed and stored. Meanwhile, 2.70 g (0.01 mol) of stearylamine was added to 100 g of benzene.
ml and further added 10 ml of triethylamine, the above nicotinic acid chloride was added at room temperature, and the mixture was stirred at 55 to 60°C for 2 hours. After reaction
Add 40 ml of water, leave to stand under ice cooling, filter the formed crystals, recrystallize from n-hexane-benzene, and obtain 3.20 g of 3-stearylcarbamide pyridine.
I got it. 20ml to 1.88g (5mmol) of the obtained crystals
of ethanol, then benzyl chloride
2.52 g (20 mmol) was added thereto and reacted under reflux for 5 hours. After the reaction, ethanol was removed by distillation, and the resulting crystals were recrystallized using petroleum ether-benzene to obtain 2.34 g of 1-benzyl-3-stearylcarbamide pyridinium chloride. When the skin external preparation of the present invention described above is to be used in ordinary cosmetics, known ingredients may be added as needed, and if necessary, moisturizers, thickening stabilizers, preservatives, and colorants may be added. , flavoring agents, etc. may be added. Cosmetics made in this way remain stable over a wide temperature range even after long-term storage.
It can be said that its commercial value is extremely high because it is extremely safe for the skin, exhibits excellent effects, and provides a good feel when used. Examples of this invention will be shown below. In addition, all compounding ratios (%) are weight %. Example 1 A cream rinse having the following composition was prepared. Group 1: 1-stearyl-3-carbamidopyridinium chloride 0.4% Cetostearyl alcohol 2.5 Parafine wax 1.0 Isopropyl palmitate 0.5 Olive oil 0.5 Fragrance 0.3 Preservative 0.2 Group 2: Pigment Appropriate amount of purified water All the rest In other words, first The mixture of the first group was heated and dissolved at 80°C, and the 80°C solution of the second group was added thereto, homogenized using a homomixer, and then cooled. The obtained cream rinse was stable for more than 3 months in an oven test at 45°C, and was non-irritating.
The usability was also very good. A cream rinse was prepared in exactly the same manner using a halide other than chlorine consisting of bromine, fluorine, and iodine instead of 1-stearyl-3-carbamidopyridinium chloride, but both showed similar properties. Ta. Example 2 A cleansing lotion having the following composition was prepared. The preparation procedure is exactly the same as in Example 1. Group 1: 1-cetyl-3-carbamidopyridinium chloride 0.8% Cetostearyl alcohol 1.2 Vaseline 5.0 Liquid paraffin 11.0 Isopropyl palmitate 2.0 Fragrance 0.1 Preservative 0.2 Group 2: 1,3-Butylene glycol 5.0 Purified water 74.7 The cleansing lotion was stable for more than 3 months in an oven test at 45°C, was non-irritating, and had a very good feel when used. Example 3 A skin cream having the following composition was prepared. Group 1: 1-stearyl-3-carbamidopyridinium chloride 1.0% Cetostearyl alcohol 5.0 Squalane 10.0 Stearic acid 8.0 Beeswax 2.0 Olive oil 3.0 Flavor 0.1 Preservatives 0.2 Group 2: 1,3-Butylene glycol 8.0 Glycerin 4.0 Purified water 58.7 The preparation procedure was exactly the same as in Example 1, and the obtained skin cream was stable for more than 3 months in an oven test at 45°C, was non-irritating, and had a very good feel when used. Example 4 A cleansing cream having the composition shown below was prepared. Group 1: 1-benzyl-3-stearylcarbamide pyridinium chloride 2.0% Cetostearyl alcohol 3.0 Liquid paraffin 35.0 Paraffin wax 2.0 Isopropyl palmitate 10.0 Group 2: Maltitol 3.0 Purified water 45.0 The preparation procedure is exactly the same as Example 1 The resulting cleansing cream was stable for more than 3 months in an oven test at 45°C, was non-irritating, and had a very good feeling of use. Example 5 A lotion having the following composition was prepared. 1st group: 1-lauryl-3-carbamidopyridinium chloride 0.60% fragrance 0.20 oleyl alcohol 0.04 1,3-butylene glycol 1.00 glycerin 1.00 2nd group: citric acid 0.07 purified water 97.06 That is, the solution consisting of the first group Two groups of aqueous solutions were added and sufficiently stirred until uniformly and transparently dissolved. The resulting transparent lotion has a mild effect on the skin, and because it solubilizes fragrances and oils without using ethyl alcohol, which is included in regular lotions, it feels very good on the skin. It was good and warm. In addition, when the bacteriostatic effect was investigated for Examples 1 to 5, a remarkable effect was observed at least for miscellaneous bacteria. Example 6 A human patch test was carried out using the following inspection method and determination method. (1) Application material Finn chamber (2) Application site: Inner upper arm (3) Application time: 24 hours (4) Judgment: 1 hour and 7 hours after removal (5) Judgment criteria: Japanese standards (-) No reaction (±) Slight erythema (+) Obvious erythema (〓) Erythema + edema or papules (〓) Erythema + edema + papules or vesicles (〓) Erythema + edema + papules + vesicles (6) Sample 0.5w/w of horn sample as active ingredient % aqueous solution was used. (a) Distilled water (blank) (b) 1-stearyl-3-carbamidopyridium chloride (inventive product) (c) Cetylpyridinium chloride (control product) (d) 1-dodecyl-3-oxypyridinium bromide (control product) (e) Cetyltrimethylammonium chloride (control product) The obtained results are shown in Table 1.
The primary irritation of -stearyl-3-carbamidopyridinium chloride (product of the present invention) is comparable to that of distilled water, and is considered to be much less irritating than other cationic surfactants (products compatible with cosmetic bases).

[Table] Example 7 An antibacterial test of 1-stearyl-3-carbamidopyridinium chloride (product of the present invention) was conducted in the following manner. Sample (a) 1-stearyl-3-carbamidopyridinium chloride (product of the present invention) (b) Cetylpyridinium chloride (control product) Test bacteria Staphylococcus aureus Test method Sample at a specified concentration Dissolve in 0.5% Tween 80 aqueous solution and keep at 30℃. Inoculate the test sample of each concentration with bacterial solution, take a loop of platinum after 30 minutes and 1 hour,
Inoculate SCD broth (manufactured by Daigo Nutrition Co., Ltd.) and observe growth. Culture conditions: 30°C, 36 hours The results obtained are summarized in Table 2. From this table, the concentration of 1-stearyl-3-carbamidopyridinium chloride showing antibacterial activity against Staphylococcus aureus was 0.1% or more, and the concentration of cetylpyridinium chloride showing antibacterial activity was 0.01% or more.
In addition, Staphylococous aureus was used as the test bacterium according to "Cosmetic Ingredients Standards 2nd Edition Commentary I" 193.
This is because we thought that this is the most representative bacterium for testing the antibacterial properties of alkylpyridinium salts, as described on page 12. Note that, considering the antibacterial properties of the product of the present invention, this effect is low considering the antibacterial properties of cetylpyridinium chloride, and it is considered that the product has bacteriostatic properties.

[Table] As is clear from the results of Examples 6 and 7 above, the skin external preparation of the present invention has been developed in the past, for example, by
It can be said that it is a highly safe surfactant that has mild bacteriostatic action compared to the surfactants disclosed in Japanese Patent Nos. 56-139462 and 139463.

Claims (1)

[Scope of Claims] 1. A skin external preparation characterized by containing a nicotinic acid derivative represented by the following general formula [A] or [B]. Record (In the formula, R ₁ represents a straight chain or branched alkyl group having 8 to 30 carbon atoms, R ₂ represents a straight chain or branched alkyl group having 1 to 30 carbon atoms and a phenyl group, and X represents a halogen group.)