JP2023117200A - Topical skin preparation - Google Patents

Abstract

To provide a novel topical skin preparation having excellent antioxidative action.SOLUTION: A topical skin preparation comprises tulip extract extracted from tulip flowers, and nicotinamide mononucleotide.SELECTED DRAWING: Figure 1

Description

TECHNICAL FIELD The present invention relates to an external preparation for skin having excellent antioxidant activity.

Antioxidant action generally means the action of inhibiting or terminating chain reactions by suppressing the production of active oxygen and free radicals, which are causative agents of oxidative stress disorders, and scavenging them. These active oxygen and free radicals are respiration by-products in vivo, and are also substances generated by physical and mental stress. Originally, living organisms have functions such as SOD (superoxide dismutase) that suppress the production of these substances, but as we age, this suppressive function declines, oxidation of the body progresses, and various diseases occur as an aging phenomenon. Connect. Since the skin is placed in a different environment from that of other organs, the effects of oxidation due to outside air, ultraviolet rays, and skin-inhabiting bacteria are significant. In particular, the aging phenomenon caused by ultraviolet rays is distinguished under the name of "photoaging", and it has been found that various aging phenomena from sunburn to wrinkles, spots, and dullness are related to active oxygen calculated by ultraviolet rays. there is Therefore, it is important not only to eat substances having antioxidant activity but also to apply them to the skin as external preparations in order to prevent aging and diseases.

Therefore, active oxygen scavenging agents and antioxidants have been investigated for the purpose of protecting against damage caused by active oxygen, and foods, cosmetics, quasi-drugs and Pharmaceutical products are being developed. For example, Patent Document 1 discloses a cosmetic containing nicotinamide mononucleotide as a characteristic component. However, nicotinamide mononucleotide has a drawback that a satisfactory moisturizing effect cannot be obtained by its single formulation (see Patent Document 2).

In addition, in Non-Patent Document 1, it is extracted from the tulip flower part for the purpose of effective utilization of the tulip flower part, which is the legitimate flower in the production process of tulip bulbs and many of which are plowed into the field. Antioxidant activity evaluation of tulip extract as a cosmetic raw material is disclosed.

However, the combination of nicotinamide mononucleotide and tulip extract has not been investigated as an anti-oxidant topical skin preparation.

JP 2016-135750 A JP 2018-145167 A

Ayaka Ota, ``Reiwa 2nd year graduation thesis, use of tulip extract as a cosmetic raw material'', Toyama Prefectural University, Faculty of Engineering, Department of Biotechnology, 2021

In view of the circumstances as described above, the present inventors conducted intensive studies and found that a combination of nicotinamide mononucleotide and a tulip extract extracted from the tulip flower part provides an excellent antioxidant effect.

An object of the present invention is to provide a novel topical preparation for skin with excellent antioxidative activity.

The external preparation for skin according to claim 1 of the present invention is characterized by containing tulip extract extracted from tulip flower parts and nicotinamide mononucleotide.

The skin external preparation according to claim 2 of the present invention is characterized by containing 0.0001% by weight to 10% by weight of each of the tulip extract and the nicotinamide mononucleotide.

The skin external preparation according to claim 3 of the present invention is characterized in that the tulip variety is Huang Komachi, and the extraction method of the tulip extract is heat extraction or normal temperature extraction.

The external preparation for skin according to claim 4 of the present invention is characterized in that the extraction solvent for the tulip extract is water, 1,3-butylene glycol or ethanol.

According to the external preparation for skin according to claim 1 of the present invention, by containing tulip extract extracted from tulip flower parts and nicotinamide mononucleotide, the SOD-like activity rate can be increased, and antioxidant Excellent action.

According to the external preparation for skin according to claim 2 of the present invention, the SOD-like activity rate can be increased by containing 0.0001% to 10% by weight of tulip extract and nicotinamide mononucleotide, respectively. , with excellent antioxidant properties.

According to the external preparation for skin according to claim 3 of the present invention, since the tulip cultivar is Huang Komachi, the SOD-like activity rate can be remarkably increased, and the antioxidative effect is excellent. Moreover, since the extraction method of the tulip extract is heat extraction or normal temperature extraction, the tulip extract can be extracted by various methods without depending on the temperature, resulting in excellent productivity.

According to the external preparation for skin according to claim 4 of the present invention, the extracting solvent for the tulip extract is water, 1,3-butylene glycol or ethanol, so that the tulip extract can be easily extracted, and the productivity is improved. Excellent for

Hereinafter, in order to describe the present invention in detail, production examples of the tulip extract used in the present invention, formulation examples of the external preparation for skin of the present invention, and experimental examples will be given as examples, but the present invention is not limited to these. do not have. In addition, % shown in Examples means % by weight unless otherwise specified.

The tulip extract used in the present invention is extracted from the flower part of the tulip genus Tulipa (scientific name: Tulipa L.) of the family Liliaceae. Tulip varieties include, for example, Kokomachi, Tateyama no Haru, Strong Gold, Amethyst, and Strawberry Star. The extraction method of the tulip extract is not particularly limited.

Examples of solvents for extracting tulip extract include water, lower alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), liquid polyhydric alcohols (1,3-butylene glycol , propylene glycol, glycerin, etc.), ketones (acetone, methyl ethyl ketone, etc.), acetonitrile, esters (ethyl acetate, butyl acetate, etc.), hydrocarbons (hexane, heptane, liquid paraffin, etc.), ethers (ethyl ether, tetrahydrofuran , propyl ether, etc.). Polar solvents such as water, lower alcohols and liquid polyhydric alcohols are preferred, and water, ethanol and 1,3-butylene glycol are particularly preferred. These solvents may be used singly or in combination of two or more.

The above tulip extract may be used as an extracted solution, or may be used after concentration, dilution, filtration treatment, decolorization with activated carbon or the like, deodorization treatment, etc., if necessary. Furthermore, the extracted solution may be subjected to a treatment such as concentration to dryness, spray drying, freeze drying, etc., and used as a dried product.

Nicotinamide mononucleotide (chemical formula: C ₁₁ H ₁₅ N ₂ O ₈ P) used in the present invention is a compound produced in the bodies of many organisms including humans. It is generally called NMN (Nicotinamide mononucleotide) and is known as an intermediate metabolite involved in the biosynthesis of coenzyme NAD+. Nicotinamide mononucleotide has two types of optical isomers, α-isomer and β-isomer, and the β-isomer is used in the present invention. Nicotinamide mononucleotide can be obtained, for example, by synthesizing nicotinamide riboside from nicotinamide and ribose, and then phosphorylating the 5-position hydroxyl group of the ribose moiety. Specifically, for example, first, nicotinamide and L-ribose tetraacetate are dissolved in anhydrous acetonitrile, an excess amount of trimethylsilyltrifluorosulfonic acid is added under a nitrogen stream, the mixture is stirred at room temperature, and methanol is added. The above-mentioned reaction mixture, in which the reaction has been terminated by sterilization, is applied to a column filled with activated charcoal, washed with distilled water, and then eluted with methanol to recover the product. Next, in order to perform a phosphorylation reaction of the 5-position hydroxyl group of the L-ribose portion of this product, the above product was dissolved in trimethoxyphosphoric acid, phosphorus oxychloride was added dropwise under ice-cooling, and the mixture was stirred under a nitrogen stream. A cold acetonitrile-ether solution is added to the above reaction mixture which has been stirred and neutralized by adding aqueous sodium hydroxide to stop the reaction. Thereafter, the lower layer (aqueous phase) is passed through an anion exchange resin to recover the reaction product, and further purified with a cation exchange resin to recover highly pure nicotinamide mononucleotide. In addition, nicotinamide mononucleotide is commercially available, and these commercial products can be purchased and used.

The above-mentioned tulip extract may be used as it is for the external preparation of the present invention, and components used in cosmetics, quasi-drugs, pharmaceuticals, foods, etc., within the range that does not impair the effects of the tulip extract and nicotinamide mononucleotide. Fats and oils, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, metal soaps, pH adjusters, preservatives, perfumes, moisturizers, powders, UV absorbers, thickeners , pigments, antioxidants, whitening agents, chelating agents, excipients, film-forming agents and the like can also be added.

The dosage forms of the present invention include, for example, lotions, creams, massage creams, milky lotions, gels, aerosols, packs, cleansers, bath agents, foundations, dusting powders, lipsticks, ointments, poultices, pastes, and plasters. , essences, powders, pills, tablets, injections, suppositories, emulsions, capsules, granules, liquids (including tinctures, liquid extracts, spirits, suspensions, limonades, etc.), etc. .

The amount of the tulip extract used in the present invention is preferably 0.0001% by weight or more, more preferably 0.0001 to 10% by weight, based on the total amount of the external preparation. Furthermore, 0.0001 to 0.10% by weight is most preferred. If it is less than 0.0001% by weight, it is difficult to expect a sufficient effect. If the content exceeds 10% by weight, the enhancement of the effect is difficult to be recognized and it is uneconomical.

The amount of the nicotinamide nucleotide used in the present invention is preferably 0.0001% by weight or more, more preferably 0.0001 to 10% by weight, based on the total amount of the external preparation. Furthermore, 0.0001 to 0.10% by weight is most preferred. If it is less than 0.0001% by weight, it is difficult to expect a sufficient effect. If the content exceeds 10% by weight, the enhancement of the effect is difficult to be recognized and it is uneconomical.

[Example 1]

[Production Example 1] Extraction at normal temperature 30 g (fresh weight) of tulip flowers of the Kokomachi cultivar is pulverized with a hammer in liquid nitrogen, 2.4 times the weight of purified water is added, and 50% by weight of 1,3-butylene glycol is added. 72 mL of an aqueous solution was added, left at room temperature for 1 week, filtered, and the filtrate was again left at room temperature for 1 week, then centrifuged and filtered to obtain a tulip extract.
[Production Example 2] Direct Steam Distillation 30 g (fresh weight) of tulip flowers of the Kokomachi variety were pulverized with a hammer in liquid nitrogen, added with three times the weight of purified water, and heated to around 105°C using a mantle heater. Steam distillation was carried out using Distillation was continued until a fraction half the amount of purified water added was obtained. The obtained distillation and distillation residue were each allowed to stand at room temperature for 1 week, then centrifuged and filtered to obtain a tulip extract.
[Manufacturing Example 3] Heating and refluxing 30 g (fresh weight) of tulip flowers of the Ki Komachi variety is pulverized with a hammer in liquid nitrogen, 2.4 times the weight of purified water is added, and the mixture is heated at 105°C for 6 hours using an autoclave. heated. It was then filtered and the resulting filtrate was divided in half. A filtrate-only fraction and a flower-containing fraction were prepared by adding the filtrate to half the amount of the filtrate residue, and 40% (v/v) of 1,3-butylene glycol was added to each. After standing at room temperature for one week, each was filtered again to obtain a tulip extract.

Next, experimental examples will be given in order to describe the effects of the present invention in detail.

[Experimental Example 1] Evaluation of SOD (superoxide dismutase)-like activity Four kinds of lotions were prepared based on the four formulations shown in Table 1, and the superoxide anion scavenging ability was measured as the SOD-like activity rate. As for the test concentration, the sample was serially diluted with ultrapure water to adjust a total of 7 concentrations, and the test was carried out. In addition, SOD Assay Kit WST (Cat No. S311, Dojindo, Japan) was used to measure superoxide anion scavenging ability. Nicotinamide mononucleotide used was manufactured by Access One Co., Ltd.
For details on the evaluation method, first, 20 μL of specimen or control, 200 μL of WST working solution, and 20 μL of Enzyme working solution were added to a 96-well plate. Dilution buffer was used as an alternative to Enzyme working solution for blanks. Three wells were used for one treatment army. The 96-well plate was then sealed with a plate seal, shaken at 270 rpm for 10 seconds, and incubated at 37° C. for 20 minutes. Absorbance at 450 nm was then measured using a microplate reader. Then, from the absorbance of the test article and the control, the superoxide anion residual rate and elimination rate of the test article were calculated by the following equations, and the SOD-like activity rate of the test article was obtained.

[Formula 1] superoxide anion residual rate (%)
= (S - SB) / (C - CB) x 100

[Formula 2] Superoxide anion scavenging rate (%)
= {(C-CB)-(S-SB)}/(C-CB)×100
= SOD-like activity rate (%)

C: absorbance of control CB: blank absorbance of control S: absorbance of test article SB: blank absorbance of test article

The results of these experiments are shown in Tables 2-5 and FIGS. 1 and 2. Table 2 shows the results of the SOD-like activity rate evaluation test for Comparative Formulation 1 (blank) in Table 1. Table 3 shows the results of the SOD-like activity rate evaluation test for comparative formulation 2 (containing 10% tulip extract) in Table 1. Table 4 shows the results of an SOD-like activity rate evaluation test for comparative formulation 3 (containing 10% nicotinamide mononucleotide (NMN)) in Table 1. Table 5 shows the results of an SOD-like activity rate evaluation test for Formulation 1 in Table 1 (containing 10% tulip extract and 10% nicotinamide mononucleotide (NMN)). In addition, FIG. 1 is a diagram showing the SOD-like activity rate of the test product at all test concentrations, and FIG. 2 is an excerpt of the main part of FIG. FIG. 3 shows the SOD-like activity rate at ˜0.10%.

As shown in FIG. 1, at all compounding concentrations of tulip extract and nicotinamide mononucleotide (10%, 5%, 1%, 0.10%, 0.01%, 0.001%, 0.0001%) , Formula 1 containing both tulip extract and nicotinamide mononucleotide has a significantly higher SOD-like activity rate than comparative formulas 2 and 3 containing tulip extract and nicotinamide mononucleotide alone. it was high. From this result, it was confirmed that the combined use of tulip extract and nicotinamide mononucleotide has a synergistic effect of increasing the rate of SOD-like activity.

Moreover, in particular, at the blending concentrations of tulip extract and nicotinamide mononucleotide shown in FIG. In contrast to the negative, the SOD-like activity of Formulation 1 turned positive and remarkably increased. From this result, it was confirmed that the combined use of tulip extract and nicotinamide mononucleotide has a synergistic effect of significantly increasing the rate of SOD-like activity at a compounding concentration of 0.0001% to 0.10% for each. .

Therefore, considering Experimental Example 1, the blending concentration of the tulip extract and nicotinamide mononucleotide is preferably 0.0001% by weight or more, more preferably 0.0001 to 10% by weight. Furthermore, 0.0001 to 0.10% by weight is most preferred.

The external preparation for skin of the present invention contains tulip extract extracted from tulip flowers and nicotinamide mononucleotide, so that the SOD-like activity rate can be increased and the antioxidative effect is excellent.

In addition, according to the skin external preparation of the present invention, by containing 0.0001% to 10% by weight of tulip extract and nicotinamide mononucleotide, respectively, the SOD-like activity rate can be increased, and the antioxidant effect can be achieved. Excellent for

Furthermore, according to the external preparation for skin of the present invention, since the tulip variety is Huang Komachi, the rate of SOD-like activity can be remarkably increased, and the antioxidative effect is excellent. Moreover, since the extraction method of the tulip extract is heat extraction or normal temperature extraction, the tulip extract can be extracted by various methods without depending on the temperature, resulting in excellent productivity.

According to the external preparation for skin of the present invention, water, 1,3-butylene glycol or ethanol is used as the extracting solvent for the tulip extract, so that the tulip extract can be easily extracted and the productivity is excellent.

FIG. 2 shows the SOD-like activity of lotion containing tulip extract and nicotinamide mononucleotide according to the present invention. FIG. 2 is an enlarged view of a main portion of FIG. 1;

Claims (4)

An external preparation for skin characterized by containing a tulip extract extracted from a tulip flower and nicotinamide mononucleotide.
2. The external preparation for skin according to claim 1, which contains 0.0001% to 10% by weight of said tulip extract and said nicotinamide mononucleotide, respectively.
3. The external preparation for skin according to claim 1, wherein the tulip variety is Huang Komachi, and the method for extracting the tulip extract is heating extraction or normal temperature extraction.
4. The external preparation for skin according to any one of claims 1 to 3, wherein the extraction solvent for said tulip extract is water, 1,3-butylene glycol or ethanol.

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