Supramolecular ionic liquid, supramolecular anti-aging compound and preparation method thereof

Abstract

The invention discloses a supramolecular ionic liquid, a supramolecular anti-aging compound and a preparation method of the supramolecular ionic liquid and the supramolecular anti-aging compound. Alpha-lipoic acid is used as a hydrogen bond donor, adenosine and trigonelline are used as receptors, low-temperature control is performed in the whole process through specific processes such as dissolution, nitrogen blowing, crystallization and freezing filtration, loss of active ingredients caused by heating is avoided as much as possible, and the supramolecular ionic liquid is prepared. Tests prove that the anti-aging composition has an excellent anti-aging effect when being applied to a cosmetic matrix formula.

Description

Technical Field

[0001] The present invention relates to the field of cosmetics, and in particular to a supramolecular ionic liquid, a supramolecular anti-aging complex and a preparation method thereof. Background Art

[0002] Supramolecular assembly technology is a self-organizing process that combines multiple molecules into ordered multi-molecular groups through non-covalent interactions. These groups can be spherical, rod-shaped or sheet-shaped samples, ranging in size from nanometers to micrometers. Supramolecular assembly technology has a wide range of applications in the fields of biology and materials science. Deep eutectic solvents (DES) are a type of ionic liquid in supramolecular assembly technology. They are two-component or three-component eutectic mixtures composed of a certain stoichiometric ratio of hydrogen bond acceptors (such as quaternary ammonium salts) and hydrogen bond donors (such as compounds such as amides, carboxylic acids and polyols), which have the advantages of being adjustable and designable.

[0003] Alpha-lipoic acid is a natural antioxidant with very strong antioxidant capacity, which is widely distributed in animal liver tissue and plants such as spinach and tomatoes. Alpha-lipoic acid belongs to vitamin B compounds and is the strongest known natural antioxidant. Its antioxidant capacity is more than 400 times that of vitamin C and vitamin E combined, and it is known as a universal antioxidant. They play an important role in the prevention and treatment of diseases related to free radicals, such as cancer, aging, diabetes, atherosclerosis, degeneration of brain and nerve tissue, and have received great attention from the international biomedical community.

[0004] α-lipoic acid is an excellent anti-aging active ingredient that can increase the level of glutathione in all cells and strengthen the entire antioxidant network. It can not only slow down endogenous aging and reduce the formation of fine lines on the skin, but also protect skin cells from ultraviolet rays and avoid exogenous photoaging. However, α-lipoic acid is a raw material that is difficult to use in the cosmetics field. The main reason is that it has poor water solubility and oil solubility, and is difficult to add to water, oil, and emulsions.

[0005] Chinese patent application CN2005101002433 discloses an α-lipoic acid-cyclodextrin derivative inclusion compound, the purpose of which is to cover the odor of α-lipoic acid, reduce its irritation, increase its water solubility and stability through the inclusion of cyclodextrin derivatives on α-lipoic acid. However, it can be seen from its examples that the inclusion rate of cyclodextrin derivatives on α-lipoic acid is very low. One part of α-lipoic acid requires more than 20 parts of cyclodextrin derivatives. When the amount of active ingredients carried is very low, it is difficult to give full play to the skin care effect of α-lipoic acid. Summary of the invention

[0006] In view of this, the present invention provides a supramolecular ionic liquid containing α-lipoic acid which is different from the prior art and is applied in the field of cosmetics to achieve good anti-aging effects.

[0007] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0008] A supramolecular ionic liquid containing alpha-lipoic acid, characterized in that it is prepared by the following method:

[0009] (1) weighing α-lipoic acid, adenosine, and trigonelline, adding them to solvent A at a solid-liquid ratio of 1:3-5, heating and dissolving to obtain a mixed solution;

[0010] (2) placing the mixed solution in a nitrogen blower to remove solvent A to obtain a crude crystalline product;

[0011] (3) dissolving the crude product in solvent B with stirring, with a solid-liquid ratio of 1:5-10; and freezing and filtering to obtain a filtrate, which is a supramolecular ionic liquid containing α-lipoic acid.

[0012] Adenosine described in the present invention is an endogenous nucleoside that is distributed throughout human cells. It can directly enter the myocardium and generate adenosine through phosphorylation, participate in myocardial energy metabolism, and also participate in dilating coronary vessels and increasing blood flow. Adenosine has physiological effects on the cardiovascular system and many other systems and tissues of the body. Adenosine is an important intermediate for synthesizing adenosine triphosphate (ATP), adenine, adenosine acid, and adenosine arabinoside.

[0013] The trigonelline described in the present invention is a plant alkaloid and the main component of coffee and fenugreek. It has anti-thrombosis, anti-diabetic, antioxidant, anti-inflammatory and neuroprotective effects. It can inhibit FcεRI-mediated intracellular signaling pathways, such as phosphorylation of PLCγ1, PI3K and Akt. In 2023, researchers at the University of Tsukuba found that supplementation with trigonelline can significantly improve the cognitive decline associated with aging in mice.

[0014] In some embodiments, the molar ratio of α-lipoic acid, adenosine and trigonelline in step (1) is 10:1-10:1-10.

[0015] In one embodiment, the molar ratio of α-lipoic acid, adenosine and trigonelline in step (1) is 7:5:2.

[0016] In some embodiments, the solvent A in step (1) is an organic solvent for α-lipoic acid, adenosine, and trigonelline, such as anhydrous ethanol, ether, dimethyl sulfoxide, and petroleum ether, or a mixture of more than one thereof. In some embodiments, the solvent A is anhydrous ethanol.

[0017] In some of the embodiments, the working parameters of the nitrogen blowdown apparatus in step (2) are a temperature of 40-45° C. and a flow rate of 0.5-1 L / min.

[0018] In some embodiments, the solvent B in step (3) is a polyol acceptable in the cosmetics field, such as ethanol, glycerol, 1,2-propylene glycol, 1,3-propylene glycol, butylene glycol, pentanediol, hexylene glycol, sorbitol, polyethylene glycol-8, polyethylene glycol-32, dipropylene glycol, diglycerol, glycerol polyether-26, polyglycerol-10, polyglycerol-8, isopentyl glycol, or a mixture of more than one thereof. In some embodiments, the solvent is isopentyl glycol.

[0019] In some embodiments, the freeze filtration in step (3) refers to placing the product at 3-5°C for 1-2 days for aging, and then performing membrane filtration using a 0.1-1 μm filter membrane.

[0020] The supramolecular ionic liquid containing α-lipoic acid prepared in the embodiment of the present invention can be used as a supramolecular anti-aging complex in a cosmetic matrix formula, and its addition amount can be 1-10wt%. The cosmetic matrix formula can be a cream, lotion, facial mask, essence, water solution, etc.

[0021] The embodiment of the present invention also discloses an anti-aging facial cream, which is composed of the following ingredients in percentage by weight: 2% of triphenin PEG-20 esters, 2% of jojoba seed oil, 5% of polydimethylsiloxane, 3% of myristyl myristate, 3% of cetearyl alcohol, 1% of glyceryl stearate, 1% of PEG-100 stearate, 0.5% of sodium polyacrylate, 5% of glycerol, 4% of propylene glycol, 3% of butylene glycol, 0.1% of sodium hyaluronate, 0.2% of allantoin, 0.05% of disodium EDTA, 0.2% of carbomer, 0.2% of arginine, 1-10% of the supramolecular ionic liquid containing alpha-lipoic acid, and the balance of water.

[0022] The beneficial effects of the technical solution provided by the embodiment of the present invention are as follows: the present invention adopts α-lipoic acid as a hydrogen bond donor, adenosine and trigonelline as receptors, and obtains a supramolecular ionic liquid by dissolving, nitrogen blowing, crystallizing, freezing and filtering and other specific processes, and controls the whole process at low temperature to avoid the loss of active ingredients caused by heating as much as possible. Tests have confirmed that the application of the supramolecular ionic liquid in the cosmetic matrix formula has excellent anti-aging effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for describing the embodiments or the prior art are briefly introduced below.

[0024] Figure 1 The wrinkle scores of each test group are shown;

[0025] Figure 2 The elasticity index R2 value of each test group is shown. DETAILED DESCRIPTION

[0026] The present invention discloses a supramolecular ionic liquid. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters to achieve it. It is particularly important to point out that all similar substitutions and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit and scope of the present invention to implement and apply the technology of the present invention.

[0027] The raw materials and reagents used in the supramolecular ionic liquid provided by the present invention can be purchased from the market.

[0028] The present invention will be further described below in conjunction with embodiments:

[0029] Example 1

[0030] A supramolecular ionic liquid containing alpha-lipoic acid is prepared by the following method:

[0031] (1) Weigh the following components in molar proportions: 10 parts of α-lipoic acid, 9 parts of adenosine, and 1 part of trigonelline, and add them to anhydrous ethanol at a solid-liquid ratio of 1:5; heat to dissolve and obtain a mixed solution;

[0032] (2) placing the mixed solution in a nitrogen blowdown apparatus, wherein the operating parameters of the nitrogen blowdown apparatus are a temperature of 40° C. and a flow rate of 1 L / min; removing ethanol to obtain a crude crystalline product;

[0033] (3) The crude product was dissolved in isoprene glycol with stirring, with a solid-liquid ratio of 1:5; the mixture was stored at 5° C. for 1 day for aging, and then filtered using a 1 μm filter membrane to obtain a filtrate, which is a supramolecular ionic liquid containing α-lipoic acid.

[0034] Example 2

[0035] A supramolecular ionic liquid containing alpha-lipoic acid is prepared by the following method:

[0036] (1) Weigh the following components in molar proportions: 10 parts of α-lipoic acid, 1 part of adenosine, and 9 parts of trigonelline, and add them to anhydrous ethanol at a solid-liquid ratio of 1:3; heat to dissolve and obtain a mixed solution;

[0037] (2) placing the mixed solution in a nitrogen blowdown apparatus, wherein the operating parameters of the nitrogen blowdown apparatus are a temperature of 45° C. and a flow rate of 0.5 L / min; removing ethanol to obtain a crude crystalline product;

[0038] (3) The crude product was dissolved in isoprene glycol with stirring, with a solid-liquid ratio of 1:10; the mixture was stored at 3° C. for 2 days for aging, and then filtered using a 0.1 μm filter membrane to obtain a filtrate, which is a supramolecular ionic liquid containing α-lipoic acid.

[0039] Example 3

[0040] A supramolecular ionic liquid containing alpha-lipoic acid is prepared by the following method:

[0041] (1) Weigh the following components in molar proportions: 7 parts of α-lipoic acid, 5 parts of adenosine, and 2 parts of trigonelline, and add them to anhydrous ethanol at a solid-liquid ratio of 1:4; heat to dissolve and obtain a mixed solution;

[0042] (2) placing the mixed solution in a nitrogen blowdown apparatus, wherein the operating parameters of the nitrogen blowdown apparatus are a temperature of 42° C. and a flow rate of 0.8 L / min; removing ethanol to obtain a crude crystalline product;

[0043] (3) The crude product was dissolved in isoprene glycol with stirring, with a solid-liquid ratio of 1:8; the mixture was stored at 4° C. for 2 days for aging, and then filtered using a 0.1 μm filter membrane to obtain a filtrate, which is a supramolecular ionic liquid containing α-lipoic acid.

[0044] Test 1: Stability Test

[0045] The supramolecular ionic liquids of α-lipoic acid prepared in Examples 1-3 were diluted with water to 10% aqueous solution, and stability was tested by heat and cold resistance accelerated aging test method. Specifically, the test object was placed in 45°C and -15°C environment for 24 hours to observe whether it was stratified, demulsified, discolored, or tasted abnormal. In order to investigate the interaction between adenosine and trigonelline as hydrogen bond acceptors and α-lipoic acid as hydrogen bond donor, comparative examples 1-2 were specially set.

[0046] Comparative Example 1

[0047] A supramolecular ionic liquid containing alpha-lipoic acid is prepared by the following method:

[0048] (1) Weigh the following components in molar proportions: 7 parts of α-lipoic acid and 7 parts of adenosine, add them to anhydrous ethanol, and the solid-liquid ratio is 1:4; heat to dissolve and obtain a mixed solution;

[0049] (2) placing the mixed solution in a nitrogen blowdown apparatus, wherein the operating parameters of the nitrogen blowdown apparatus are a temperature of 42° C. and a flow rate of 0.8 L / min; removing ethanol to obtain a crude crystalline product;

[0050] (3) The crude product was dissolved in isoprene glycol with stirring, with a solid-liquid ratio of 1:8; the mixture was stored at 4° C. for 2 days for aging, and then filtered using a 0.1 μm filter membrane to obtain a filtrate, which is a supramolecular ionic liquid containing α-lipoic acid.

[0051] Comparative Example 2

[0052] A supramolecular ionic liquid containing alpha-lipoic acid is prepared by the following method:

[0053] (1) Weigh the following components in molar proportions: 7 parts of α-lipoic acid and 7 parts of trigonelline, add them into anhydrous ethanol, and the solid-liquid ratio is 1:4; heat to dissolve and obtain a mixed solution;

[0054] (2) placing the mixed solution in a nitrogen blowdown apparatus, wherein the operating parameters of the nitrogen blowdown apparatus are a temperature of 42° C. and a flow rate of 0.8 L / min; removing ethanol to obtain a crude crystalline product;

[0055] (3) The crude product is dissolved in isoprene glycol with stirring, with a solid-liquid ratio of 1:8; the mixture is stored at 4° C. for 2 days for aging, and then filtered using a 0.1 μm filter membrane to obtain a filtrate, which is a supramolecular ionic liquid containing α-lipoic acid.

[0056] The 10% aqueous solution of the supramolecular ionic liquid samples prepared in the above Examples 1-3 and Comparative Examples 1-2 was placed at 45°C, -15°C, and 25°C for 24 hours. After returning to room temperature, observe whether there is any obvious difference in properties compared with before the test. The specific test results are shown in Table 1.

[0057] Table 1 Stability test records

[0058] Test Group 45℃ -15℃ 25℃ Example 1 pass pass pass Example 2 pass pass pass Example 3 pass pass pass Comparative Example 1 pass There is sediment at the bottom, not passing pass Comparative Example 2 pass There is sediment at the bottom, not passing pass

[0059] As can be seen from Table 1, the 10% aqueous solution of the supramolecular ionic liquid samples prepared in Examples 1-3 of the present invention has good stability. Although Comparative Example 1-2 passed the heat resistance and 25°C room temperature tests, the antifreeze performance is relatively poor. When the product is sold or used in cold seasons, the precipitation of active ingredients may affect the shelf life of the product. It can be seen that the combination of adenosine and trigonelline as hydrogen bond acceptors and hydrogen bond donor α-lipoic acid can form a more water-soluble supramolecular assembly, which is conducive to the more flexible use of the product as an efficacy additive in the cosmetic matrix.

[0060] Test 2: Efficacy Evaluation

[0061] Aging is a complex natural physiological process. The main factors affecting skin aging include endogenous factors and exogenous factors. Endogenous factors mainly include genetic theory, free radical theory, non-enzymatic glycosylation aging theory, etc. Exogenous factors mainly include photoaging, tobacco, environmental pollution, etc. The significant clinical manifestations of skin aging are dry skin, rough skin, pigmentation, loose skin, reduced elasticity, wrinkles, etc. At present, there are many methods and indicators for evaluating the anti-aging of products, such as skin moisture content, skin texture, wrinkles, skin elasticity, etc. Among them, measuring the changes in skin wrinkles and elasticity is a reliable method recognized by the industry.

[0062] In order to test the skin care efficacy of the supramolecular ionic liquid prepared in the embodiment of the present invention as a supramolecular anti-aging complex, it is applied in cosmetic formulations to evaluate its efficacy on human body. In order to investigate the interaction between adenosine and trigonelline as hydrogen bond acceptors and α-lipoic acid as hydrogen bond donor, comparative examples 3-4 are set.

[0063] Example 4

[0064] An anti-aging facial cream is composed of the following ingredients in percentage by weight: 2% of tribehenin PEG-20 esters, 2% of jojoba seed oil, 5% of polydimethylsiloxane, 3% of myristyl myristate, 3% of cetearyl alcohol, 1% of glyceryl stearate, 1% of PEG-100 stearate, 0.5% of sodium polyacrylate, 5% of glycerol, 4% of propylene glycol, 3% of butylene glycol, 0.1% of sodium hyaluronate, 0.2% of allantoin, 0.05% of disodium EDTA, 0.2% of carbomer, 0.2% of arginine, 5% of the supramolecular ionic liquid containing alpha-lipoic acid prepared in Example 3, and the balance of water.

[0065] Comparative Example 3

[0066] An anti-aging facial cream is composed of the following ingredients in percentage by weight: 2% of tribehenin PEG-20 esters, 2% of jojoba seed oil, 5% of polydimethylsiloxane, 3% of myristyl myristate, 3% of cetearyl alcohol, 1% of glyceryl stearate, 1% of PEG-100 stearate, 0.5% of sodium polyacrylate, 5% of glycerol, 4% of propylene glycol, 3% of butylene glycol, 0.1% of sodium hyaluronate, 0.2% of allantoin, 0.05% of disodium EDTA, 0.2% of carbomer, 0.2% of arginine, 5% of supramolecular ionic liquid containing alpha-lipoic acid prepared in comparative example 1, and the balance of water.

[0067] Comparative Example 4

[0068] An anti-aging facial cream is composed of the following ingredients in percentage by weight: 2% of tribehenin PEG-20 esters, 2% of jojoba seed oil, 5% of polydimethylsiloxane, 3% of myristyl myristate, 3% of cetearyl alcohol, 1% of glyceryl stearate, 1% of PEG-100 stearate, 0.5% of sodium polyacrylate, 5% of glycerol, 4% of propylene glycol, 3% of butylene glycol, 0.1% of sodium hyaluronate, 0.2% of allantoin, 0.05% of disodium EDTA, 0.2% of carbomer, 0.2% of arginine, 5% of supramolecular ionic liquid containing alpha-lipoic acid prepared in comparative example 2, and the balance of water.

[0069] Volunteers were organized to evaluate the anti-aging effects of Example 4 and Comparative Examples 3-4, and the evaluation indicators were skin wrinkles and skin elasticity.

[0070] 90 volunteers with crow's feet at the corners of their eyes were recruited, regardless of gender, aged 45-65 years old, and the test area had no obvious interference factors such as birthmarks, acne, and scars. The subjects used the product for 4 consecutive weeks and were required to store the product in an environment above 25°C. After cleansing the skin, the volunteers took an appropriate amount of sample and applied it to the face, once in the morning and once in the evening. On the 0th day and the 28th day, the skin wrinkles and skin elasticity were measured.

[0071] Skin wrinkles are collected using VISIA to obtain wrinkle scores. The wrinkle score reflects the size, area and density of eye wrinkles. The higher the value, the greater the size, area and density of eye wrinkles. See the attached test results for specific results. Figure 1 .

[0072] Skin elasticity is measured using the skin elasticity tester Cutometer MPA580 to measure the elasticity index R2 value. The R2 value refers to the ratio of the skin's rebound amount when there is no negative pressure to the maximum stretch amount when there is negative pressure. The closer the R2 value is to 1, the better the skin elasticity. See the attached for specific test results. Figure 2 .

[0073] from Figure 1 , Figure 2 It can be seen that the anti-aging cream prepared in Example 4 of the present invention can effectively reduce the skin wrinkle score and improve skin elasticity, showing good anti-aging effect. In addition, the anti-aging effect of Example 4 is significantly better than that of Comparative Examples 3-4 containing only one of adenosine and trigonelline.

[0074] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A supramolecular ionic liquid containing α-lipoic acid, characterized in that: Prepared by the following method: (1) weighing α-lipoic acid, adenosine, and trigonelline, adding them to solvent A at a solid-liquid ratio of 1:3-5, heating and dissolving to obtain a mixed solution; (2) placing the mixed solution in a nitrogen blower to remove solvent A to obtain a crude crystalline product; (3) dissolving the crude product in solvent B with stirring, with a solid-liquid ratio of 1:5-10; and freezing and filtering to obtain a filtrate, which is a supramolecular ionic liquid containing α-lipoic acid.

2. The supramolecular ionic liquid containing α-lipoic acid according to claim 1, characterized in that The molar ratio of α-lipoic acid, adenosine and trigonelline in step (1) is 10:1-10:1-10.

3. The supramolecular ionic liquid containing α-lipoic acid according to claim 2, characterized in that: The molar ratio of α-lipoic acid, adenosine and trigonelline in step (1) is 7:5:

2.

4. The supramolecular ionic liquid containing α-lipoic acid according to claim 1, characterized in that The solvent A in step (1) is one or a mixture of anhydrous ethanol, ethyl ether, dimethyl sulfoxide, petroleum ether.

5. The supramolecular ionic liquid containing α-lipoic acid according to claim 4, characterized in that: The solvent A is anhydrous ethanol.

6. The supramolecular ionic liquid containing α-lipoic acid according to claim 1, characterized in that The working parameters of the nitrogen blowing apparatus in step (2) are a temperature of 40-45° C. and a flow rate of 0.5-1 L / min.

7. The supramolecular ionic liquid containing α-lipoic acid according to claim 1, characterized in that: The solvent B in step (3) is one or a mixture of more than one of ethanol, glycerol, 1,2-propylene glycol, 1,3-propylene glycol, butylene glycol, pentanediol, hexylene glycol, sorbitol, polyethylene glycol-8, polyethylene glycol-32, dipropylene glycol, diglycerol, glycerol polyether-26, polyglycerol-10, polyglycerol-8, and isopentyl glycol in the cosmetic field.

8. The supramolecular ionic liquid containing α-lipoic acid according to claim 1, characterized in that: The freeze filtration described in step (3) refers to placing the product in an environment of 3-5°C for 1-2 days for aging, and then performing membrane filtration using a 0.1-1 μm filter membrane.

9. Use of the supramolecular ionic liquid containing α-lipoic acid according to any one of claims 1 to 8 in the manufacture of cosmetics.

10. An anti-aging facial cream, characterized in that: The invention is composed of the following ingredients in percentage by mass: 2% of tribehenin PEG-20 esters, 2% of jojoba seed oil, 5% of polydimethylsiloxane, 3% of myristyl myristate, 3% of cetearyl alcohol, 1% of glyceryl stearate, 1% of PEG-100 stearate, 0.5% of sodium polyacrylate, 5% of glycerol, 4% of propylene glycol, 3% of butylene glycol, 0.1% of sodium hyaluronate, 0.2% of allantoin, 0.05% of disodium EDTA, 0.2% of carbomer, 0.2% of arginine, 1-10% of the supramolecular ionic liquid containing α-lipoic acid according to any one of claims 1 to 8, and the balance of water.

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