Synergistic antioxidant composition containing folic acid

Abstract

The invention provides a synergistic antioxidant composition containing folic acid. The composition comprises the following components in percentage by weight: 0.25-1.25% of folic acid, 2-5% of glycine, 1-5% of arginine, 1-5% of a stabilizing agent, 1-5% of a stabilizing agent, 1-5% of a stabilizing agent, 1-5% of a stabilizing agent and the balance of water. The weight ratio of the folic acid to the glycine to the arginine is (0.05-0.7): 1: (0.2-2); the pH value of the composition is 7-9.

Description

Technical Field

[0001] This invention relates to the fields of fine chemicals and cosmetics, specifically to a folic acid-containing synergistic antioxidant composition, its preparation method, and its application. Background Technology

[0002] The skin is one of the largest organs in the human body and serves as the first natural barrier protecting the body from external aggressors. Normal bodily functions inevitably produce free radicals, but the body's own antioxidant defense system effectively eliminates them. Therefore, a healthy body maintains a dynamic balance between free radical production and elimination, preventing damage. It is well known that excessive exposure to solar radiation, smoking, and environmental pollution can trigger the production of excessive free radicals. These excess free radicals damage the skin's physiological structure, leading to dullness, lack of radiance, sagging, age spots, wrinkles, and other signs of aging.

[0003] Antioxidants are an important component of cosmetics, possessing the ability to inhibit cell damage. Topical application of antioxidants to the skin is crucial for minimizing skin aging and better protecting the skin from harmful free radicals. For the product itself, antioxidants can prevent and delay the discoloration reactions of other active ingredients in cosmetics and can prevent the oxidative rancidity of the oils used. Currently, commonly used antioxidants in cosmetics are divided into two categories: one is enzymatic antioxidants, mainly including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and the thioredoxin (Trx) system; the other is non-enzymatic antioxidants, mainly including vitamin C, vitamin E, coenzyme Q10, glutathione, alpha-lipoic acid, carotenoids, and natural plant polyphenols.

[0004] Existing work focuses more on finding natural or highly effective antioxidants. For example, Chinese patent CN107106464B provides an antioxidant containing enzymatically synthesized glycogen (ESG) or its α-amylase digest (RG); Chinese patent CN100333709C provides an antioxidant containing acerola cherry seeds as an active ingredient that has high antioxidant activity and can be used in cosmetics by treating acerola cherry seeds, which are treated as waste.

[0005] Arginine (L-Arginine) is a semi-essential amino acid widely found in various foods, such as meat, fish, dairy products, and nuts. It plays a number of important physiological functions and provides numerous health benefits in the human body, including promoting cardiovascular health, enhancing immune function, improving athletic performance, promoting wound healing, and possessing antioxidant properties. Arginine exhibits significant antioxidant activity, mitigating oxidative stress-induced cell damage by activating the NRF2 signaling pathway and other antioxidant enzyme systems. Furthermore, arginine slows down cellular aging by inhibiting the activity of the autophagy enzyme EP300. Arginine can also improve mitochondrial efficiency and promote energy metabolism, thereby alleviating fatigue-related discomfort.

[0006] Glycine, the simplest amino acid in nature with the chemical formula C2H5NO2, possesses numerous important physiological functions and health benefits. While a non-essential amino acid, glycine, as one of the basic building blocks of proteins, participates in protein synthesis in the body, providing raw materials for cell division and growth. Furthermore, glycine can convert α-keto acids into non-essential amino acids via mesolysis, meeting the body's needs. Glycine is a key component of glutathione (GSH), a powerful antioxidant that scavenge free radicals and protects cells from oxidative damage. In addition, glycine metabolism in the liver promotes glycogen storage or its conversion into other nitrogenous compounds, thereby improving liver function.

[0007] Glycine can enhance the body's immunity by promoting the energy metabolism and function of immune cells, thereby strengthening the body's disease resistance. In addition, it has anti-inflammatory effects, inhibiting inflammatory responses. Glycine has antispasmodic properties, relieving tension in gastrointestinal smooth muscle and reducing abdominal pain and muscle spasms. It can also alleviate fatigue by regulating neurotransmitter balance. Glycine plays a significant role in cardiovascular health. It can reduce the risk of acute myocardial infarction, inhibit chronic rejection of aortic dissection, and improve angiogenesis through its antioxidant effects. Furthermore, glycine also has antihypertensive effects.

[0008] Glycine has anti-aging properties, slowing down cell aging and reducing oxidative stress. Furthermore, it is used to treat mental illnesses such as schizophrenia and depression by improving cognitive function through regulating neurotransmitter balance. Glycine can also inhibit the release of inflammatory factors and reduce immune responses.

[0009] Folic acid, also known as vitamin B9, is a water-soluble vitamin and a common cosmetic ingredient widely used in skincare, haircare, and functional skincare products. Its main functions include anti-oxidation, anti-aging, moisturizing, and repairing the skin barrier. These properties make folic acid a key ingredient in high-end skincare products, helping consumers resist environmental damage to the skin, slow down the aging process, and achieve healthy beauty "from the inside out."

[0010] While the antioxidant properties of raw materials for other applications, such as skin protectants, have received little attention, this application unexpectedly discovered that arginine, glycine, and folic acid, as skin protectants, possess free radical scavenging capabilities against dibenzopicrin (DPPH) free radicals. DPPH is a very stable nitrogen-centered free radical; if the test substance can scavenge it, it suggests that the test substance has the effective ability to reduce the concentration of free radicals such as hydroxyl radicals, alkyl radicals, or peroxide radicals, thereby interrupting the lipid peroxidation chain reaction. Therefore, this application finds that the combination of arginine, glycine, and folic acid not only has synergistic antioxidant properties but also skin-protective effects, providing better protection for the skin. Summary of the Invention

[0011] On one hand, the present invention provides a folic acid-containing synergistic antioxidant composition comprising: 0.25-1.25% by weight of folic acid, 2-5% by weight of glycine, 1-5% by weight of arginine; and water, wherein the weight ratio of folic acid, glycine and arginine is 0.05-0.7:1:0.2-2; and the pH value of the composition is 7-9.

[0012] In a preferred embodiment, the weight ratio of folic acid, glycine and arginine in the composition of the present invention is 0.1875-0.416:1:0.25-1.67.

[0013] In a preferred embodiment, the composition of the present invention contains 0.5-1.25% by weight of folic acid.

[0014] In a preferred embodiment, the composition of the present invention contains 3-5% by weight of glycine.

[0015] In a preferred embodiment, the composition of the present invention comprises: 0.5% by weight of folic acid, 5% by weight of glycine, and 1% by weight of arginine.

[0016] In a preferred embodiment, the composition of the present invention comprises: 0.75% by weight of folic acid, 3-4% by weight of glycine, and 1-5% by weight of arginine.

[0017] In a preferred embodiment, the composition of the present invention comprises: 1.25% by weight of folic acid, 2-3% by weight of glycine, and 4-3% by weight of arginine.

[0018] In a preferred embodiment, the composition of the present invention has a DPPH scavenging rate of ≥49.24%.

[0019] On the other hand, the present invention also relates to a method for preparing the synergistic antioxidant composition, comprising the following steps: weighing folic acid, glycine and arginine, adding deionized water to make up to 100 parts by mass, mixing evenly, and allowing to stand to obtain the composition of the present invention.

[0020] In another aspect, the present invention also relates to a topical skin formulation of the folic acid-containing synergistic antioxidant composition, wherein the antioxidant composition is present in a content of 1-9 by weight in the topical skin formulation. Detailed Implementation

[0021] The present invention will be further illustrated below with reference to specific embodiments. However, these embodiments do not constitute any limitation on the present invention and are only used to illustrate the present invention. Any limited modifications made within the scope of the claims of the present invention are still within the scope of the claims of the present invention.

[0022] The present invention aims to provide a synergistic antioxidant composition containing folic acid, comprising: 0.25-1.25% by weight of folic acid, 2-5% by weight of glycine, 1-5% by weight of arginine; and water, wherein the weight ratio of folic acid, glycine, and arginine is 0.05-0.7:1:0.2-2; and the pH value of the composition is 7-9. This composition not only possesses synergistic antioxidant properties but also has skin-protective effects, providing better protection for the skin.

[0023] To provide a more concise description, some of the quantitative expressions given herein are not modified by the term "approximately". It should be understood that, whether or not the term "approximately" is explicitly used, each quantity given herein is intended to refer to an actual given value, and also to an approximation of such given values ​​that can be reasonably inferred by one of ordinary skill in the art, including approximations of such given values ​​caused by experimental and / or measurement conditions.

[0024] folic acid Folic acid, a water-soluble vitamin, is a common cosmetic ingredient, but its solubility is poor. In water, folic acid has extremely low solubility, only 0.0016 mg / ml (i.e., 1.6 mg / L). Mixing folic acid with glycine and arginine in a certain proportion can significantly improve its solubility and also yield an excellent antioxidant synergistic composition.

[0025] In some embodiments, the compositions of the present invention contain 0.25-1.25% by weight of folic acid.

[0026] In a specific implementation, the present invention uses Folic Acid, a product purchased from DSM Nutritional Products Ltd.

[0027] Arginine Arginine possesses significant antioxidant properties, mitigating oxidative stress-induced cell damage by activating the NRF2 signaling pathway and other antioxidant enzyme systems. Furthermore, arginine delays cellular senescence by inhibiting the activity of the autophagy enzyme EP300. However, arginine production is costly, especially given rising raw material prices; therefore, more cost-effective antioxidant additives are needed.

[0028] In some embodiments, the compositions of the present invention contain 1-5% by weight of arginine.

[0029] In a specific implementation, the present invention uses L-arginine, a product purchased from Shanghai Xiehe Amino Acid Co., Ltd.

[0030] glycine Glycine is a potent antioxidant that scavenge free radicals, protects cells from oxidative damage, and inhibits inflammatory responses, thereby reducing the risk of various chronic diseases. As a non-essential amino acid, glycine is generally well-tolerated with few adverse reactions. It has wide applications in food, pharmaceuticals, and cosmetics, such as as a sweetener, buffer, and antioxidant. Although glycine is already used as an antioxidant in cosmetics, the cosmetic industry still needs more cost-effective antioxidant additives.

[0031] In some embodiments, the compositions of the present invention contain 2-5% by weight of glycine. Preferably, the compositions of the present invention contain 3-5% by weight of glycine.

[0032] In a specific implementation, the present invention uses glycine, a product purchased from Hebei Huayang Biotechnology Co., Ltd.

[0033] Synergistic Antioxidant Composition This invention provides a synergistic antioxidant composition containing folic acid.

[0034] The synergistic antioxidant composition of the present invention comprises: 0.25-1.25% by weight of folic acid, 2-5% by weight of glycine, 1-5% by weight of arginine; and water, wherein the weight ratio of folic acid, glycine and arginine is 0.05-0.7:1:0.2-2; and the pH value of the composition is 7-9.

[0035] In some embodiments, the weight ratio of glycine to arginine is 2:1 to 5:1.

[0036] In some embodiments, the pH value of the composition is 7.24-8.99.

[0037] In some embodiments, the composition contains 0.5-1.25% by weight of folic acid.

[0038] In some embodiments, the composition contains 3-5% by weight of glycine.

[0039] In some embodiments, the composition comprises: 0.5% by weight folic acid, 5% by weight glycine, and 1% by weight arginine.

[0040] In some embodiments, the composition comprises: 0.75% by weight folic acid, 3-4% by weight glycine, and 1-5% by weight arginine.

[0041] In some embodiments, the composition comprises: 1.25% by weight folic acid, 2-3% by weight glycine, and 4-3% by weight arginine.

[0042] In some embodiments, the composition is in the form of an aqueous solution.

[0043] Preparation method of the composition This invention also relates to a method for preparing a synergistic antioxidant composition. Specifically, the method includes the following steps: weighing folic acid, glycine, and arginine, adding deionized water to a final volume of 100 parts by weight, mixing thoroughly, and allowing to stand to obtain the composition of this invention.

[0044] Topical skin agents The topical skin agent of this invention, in some specific embodiments, is a composition containing folic acid, glycine, and arginine, which can be used as an efficacy additive in the preparation of the topical skin agent. The topical skin agent is preferably a cosmetic composition, including but not limited to the preparation of products in dosage forms such as creams, lotions, and sprays. The ratio of folic acid, glycine, and arginine in the topical skin agent is 0.75:3:5-0.75:4:1 and 1.25:3:3-1.25:4:2.

[0045] The present invention will be further illustrated below with reference to specific embodiments. It is important to note that these embodiments are for illustrative purposes only and should not be construed as limiting the scope of protection of the invention. Those skilled in the art can make non-essential improvements and adjustments based on the above description of the invention. Test methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions or as recommended by the manufacturer. Unless otherwise stated, all percentages and parts are by weight.

[0046] Example The experimental materials used in the embodiments of the present invention are as follows: Glycine, trade name: glycine, purchased from Hebei Huayang Biotechnology Co., Ltd.; Arginine, trade name: L-arginine, purchased from Shanghai Xiehe Amino Acid Co., Ltd.; Folic acid, brand name: Folic Acid, purchased from DSM Nutritional Products Ltd; The water used in the experiment was deionized water prepared in the laboratory. Anhydrous ethanol was purchased from Sinopharm Chemical Reagent Co., Ltd. DPPH solution, purchased from SIGMA; The ultraviolet-visible spectrometer, model CARY 100 Conc, with a test wavelength of 517 nm, was purchased from VARIAN. pH meter, SevenExcellence S500-Basic, purchased from Mettler.

[0047] Example 1: Preparation of an antioxidant composition Weigh out folic acid, glycine, and arginine according to the formula, and add deionized water to a final volume of 100 parts by weight. Let stand at room temperature and pressure, protected from light, until the sample is completely dissolved before proceeding with the experiment.

[0048] Table 1. Content of each component in the antioxidant compositions prepared in Examples 1-15 Table 2 shows the content of each component in the antioxidant compositions prepared in Examples 16-27. Table 3 shows the content of each component in the antioxidant compositions prepared in Examples 28-40. Examples 1-15 are for individual raw materials, while Examples 16-40 are for formulations of three raw materials tested in an orthogonal experiment.

[0049] Test Example 1: Visual Observation and pH Measurement The pH value of the compositions prepared in Examples 1-40 was measured, and their appearance was observed at room temperature and pressure.

[0050] Table 4. pH values ​​and appearance of the compositions prepared in Examples 1-10 Table 5. pH values ​​and appearance of the compositions prepared in Examples 11-20 Table 6. pH values ​​and appearance of the compositions prepared in Examples 21-30 Table 7. pH values ​​and appearance of the compositions prepared in Examples 31-40 Because folic acid is poorly soluble and requires neutralization with an alkaline substance to dissolve, Examples 1-5 could not be prepared. Glycine has a weakly acidic pH, while arginine solution has a higher pH. Examples 6-40, which combine the three, are all transparent liquids, indicating that folic acid has been completely dissolved. Furthermore, the pH of the compounded compositions is alkaline. In addition to being used as a skin protectant, these compositions can also be used to adjust the pH of the system.

[0051] Test Example 2: DPPH Free Radical Scavenging Rate Determination The DPPH free radical scavenging rate of the compositions prepared in Examples 1-15 was determined.

[0052] DPPH solution: Accurately weigh 20 mg of DPPH, dissolve it in anhydrous ethanol, and dilute to a final volume of 250 mL in a volumetric flask. The DPPH concentration is then 2 × 10⁻⁶. -4 mol / L. Take 100 μL of the test solution and an equal volume of 2 × 10⁻⁶ mol / L. -4 Add mol / L DPPH solution to the wells of the same 96-well plate, mix thoroughly, and incubate the plate at room temperature for 30 min in the dark (the incubation time should be fixed to ensure the free radical reaction reaches equilibrium). Use a microplate reader to measure the absorbance of the blank group, sample group, and background group sequentially at 517 nm. After 30 min, use anhydrous ethanol as a reference to measure the absorbance (Ai). 2 × 10⁻⁶ -4 The absorbance of a mixture of mol / L DPPH solution and an equal volume of anhydrous ethanol is Ac; the absorbance of the test solution and an equal volume of anhydrous ethanol mixture is Aj. Calculate the clearance rate using the following formula: Clearance rate = [1 - (Ai - Aj) / Ac] × 100% Ac: Absorbance of DPPH solution without test solution; absorbance of blank group (absorbance of DPPH and solvent only, representing the initial free radical concentration).

[0053] Ai: Absorbance of DPPH solution when the test solution is added; Absorbance of sample group (absorbance of residual free radicals after the sample reacts with DPPH).

[0054] Aj: Absorbance of the test liquid at the measurement wavelength, background absorbance of the sample (absorbance of the sample itself at 517nm, eliminating background interference).

[0055] The DPPH scavenging rates of Examples 1-40 were determined respectively. Table 8. DPPH removal rates in Examples 1-10 Table 9. DPPH removal rates in Examples 11-20 Table 10, DPPH removal rates in Examples 21-30 Table 11, DPPH removal rates in Examples 31-40 Examples 1-15 show that, except for the folic acid solution which could not be prepared, both glycine and arginine solutions exhibited certain DPPH scavenging abilities, with arginine showing slightly better performance than glycine. Based on the results of Examples 16-40, the range of folic acid in the orthogonal experiment was 18.44, the range of glycine was 13.78, and the range of arginine was 15.08, indicating that the order of influence of the composition on DPPH free radical scavenging rate was folic acid, arginine, and glycine, consistent with the results of individual ingredient tests. Folic acid exhibited the best antioxidant capacity after dissolution, which is likely related to its structure. The benzene ring and heterocyclic structure in folic acid can better stabilize electrons and more easily accept electrons, thus resulting in the highest DPPH scavenging rate. Similarly, the structure of arginine is also more likely to gain electrons than glycine, thus its effect on DPPH scavenging rate is more significant. Examples 28, 29, 37, and 38 showed the highest DPPH free radical scavenging rates, which were higher than the highest among individual ingredients in Example 7, indicating that the combination of the three ingredients can improve antioxidant capacity. Test Example 37 showed the best results, with a scavenging rate of 57.84%. The range results also showed that the three ingredients had similar effects on the DPPH scavenging rate, and none of them significantly affected the DPPH scavenging rate. The dosage of the three ingredients in Examples 28, 29, 37, and 38 did not show a clear bias, consistent with the previous results. This indicates that the antioxidant effect of the composition is formed by the combined action of the three ingredients, and no single ingredient plays a decisive role.

[0056] Based on the examples and test cases, it is believed that folic acid, glycine and arginine all have DPPH free radical scavenging ability, and the combination of the three can enhance the antioxidant capacity, thus obtaining a composition with antioxidant capacity.

[0057] Application examples The composition containing folic acid, glycine, and arginine described in this invention can be used as an efficacy additive in the preparation of topical skin agents. The topical skin agent is preferably a cosmetic composition, including but not limited to the preparation of products in dosage forms such as creams, lotions, and sprays. The ratio of folic acid, glycine, and arginine in the topical skin agent is between 0.75:3:5 and 0.75:4:1 and between 1.25:3:3 and 1.25:4:2, with the total ratio not exceeding 15%. The following are specific examples of the application of compositions containing folic acid, glycine, and arginine in topical skin preparations, including creams, lotions, and sprays, as well as the formulations and preparation methods of these dosage forms. Specific applications are as follows: Application Example 1: Preparation of Creams and Ointments Process: Heat phase A to 80℃, disperse it evenly under homogenization, and add phase B heated to 80℃. After adding, homogenize for 5 minutes, stir and cool to 55℃, add phase C, stir and cool to 50℃, add phase D, homogenize for 3 minutes, stir and cool to 35℃ to obtain the final product.

[0058] Application Example 2: Emulsion Preparation Process: Heat phase A to 80℃, disperse it evenly under homogenization, and add phase B heated to 80℃. After adding, homogenize for 5 minutes, stir and cool to 55℃, add phase C, stir and cool to 50℃, add phase D, homogenize for 3 minutes, stir and cool to 35℃ to obtain the final product.

[0059] Application Example 3: Preparation of Spray Process: Heat phase A to 80℃, disperse it evenly under homogenization, and add phase B heated to 80℃. After adding, homogenize for 5 minutes, stir and cool to 55℃, add phase C, stir and cool to 50℃, add phase D, homogenize for 3 minutes, stir and cool to 35℃ to obtain the final product.

Claims

1. A folic acid-containing synergistic antioxidant composition comprising: 0.25-1.25% by weight of folic acid, 2-5% by weight of glycine, 1-5% by weight of arginine; and water, wherein the weight ratio of folic acid, glycine and arginine is 0.05-0.7:1:0.2-2; and the composition has a pH of 7-9.

2. The composition according to claim 1, characterized in that, The weight ratio of folic acid, glycine and arginine in the composition is 0.1875-0.416:1:0.25-1.

67.

3. The composition according to claim 1, characterized in that, The composition contains 0.5-1.25% by weight of folic acid.

4. The composition according to claim 1, characterized in that, The composition contains 3-5% by weight of glycine.

5. The composition according to claim 1, characterized in that, The composition comprises: 0.5% by weight folic acid, 5% by weight glycine, and 1% by weight arginine.

6. The composition according to claim 1, characterized in that, The composition comprises: 0.75% by weight folic acid, 3-4% by weight glycine, and 1-5% by weight arginine.

7. The composition according to claim 1, characterized in that, The composition comprises: 1.25% by weight folic acid, 2-3% by weight glycine, and 4-3% by weight arginine.

8. The composition according to claim 1, characterized in that, The composition has a DPPH scavenging rate of ≥49.24%.

9. A method for preparing the composition according to any one of claims 1-8, comprising the following steps: Weigh out folic acid, glycine and arginine, and add deionized water to make up to 100 parts by weight. Mix them evenly and let them stand to obtain the composition of the present invention.

10. A topical skin formulation comprising the folic acid-containing synergistic antioxidant composition according to any one of claims 1-8, characterized in that, The antioxidant composition is present in a content of 1-9% by weight in the topical skin preparation.

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