CN114010522A - Lipoic acid mixed micelle and preparation method and application thereof - Google Patents

Lipoic acid mixed micelle and preparation method and application thereof Download PDF

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CN114010522A
CN114010522A CN202111578503.3A CN202111578503A CN114010522A CN 114010522 A CN114010522 A CN 114010522A CN 202111578503 A CN202111578503 A CN 202111578503A CN 114010522 A CN114010522 A CN 114010522A
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lipoic acid
micelle
acid mixed
mixed micelle
phospholipid
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李建波
张金洁
徐雅茹
栗庆连
王辰旭
吴哲
杨洋
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Zhengzhou University
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Abstract

The invention discloses a lipoic acid mixed micelle which is prepared from lipoic acid, phospholipid and sodium lipoate, has simple components and high drug loading capacity, has stronger stability, and can still maintain the properties of the micelle after different dilution times and long-term storage. The invention also discloses a preparation method of the mixed micelle, which has simple process and high repeatability and is suitable for industrial production. And the mixed micelle does not need ethanol, propylene glycol and other organic solvents with large stimulation for solubilization, and the obtained mixed micelle has no side effect when in use, is safe and reliable, has wide raw material sources and low cost. The invention also discloses the application of the mixed micelle, the mixed micelle can be used for preparing cosmetics and pharmaceutical excipients acceptable in pharmacy to prepare a pharmaceutical composition, and the lipoic acid mixed micelle can be prepared into injections, oral preparations and skin coatings, can be diluted to different degrees and then used, and is greatly convenient for clinical administration.

Description

Lipoic acid mixed micelle and preparation method and application thereof
Technical Field
The invention relates to a lipoic acid mixed micelle, in particular to a lipoic acid mixed micelle and a preparation method and application thereof.
Background
Alpha-lipoic acid (ALA) is a natural antioxidant with very strong antioxidant capacity and is widely distributed in liver tissues of animals and plants such as spinach and tomato. Lipoic acid belongs to vitamin B compounds, and functions as a coenzyme in multienzyme complexes such as pyruvate dehydrogenase, α -ketoglutarate dehydrogenase, and aminocaproate decarboxylase. In recent years, the oxidation resistance of lipoic acid has received more and more attention, and it has become a hot spot of research in the scientific community. Alpha-lipoic acid (ALA, oxidized form) can be converted into dihydrolipoic acid (DHLA, reduced form) in vivo, ALA and DHLA both have strong inoxidizability, and the ALA and DHLA play a synergistic effect in vivo, are one of known natural antioxidants with the strongest effect, have more than 400 times of the combined ability of vitamin C and vitamin E in the antioxidant ability, and are known as 'universal antioxidants'. They play an important role in the prevention and treatment of diseases associated with free radicals, such as cancer, aging, diabetes, atherosclerosis, degeneration of brain and nervous tissues, etc.
In the field of cosmetics, alpha-lipoic acid is considered as a general antioxidant which increases the level of glutathione in all cells, and has whitening, spot-removing, and anti-aging effects. Internationally, alpha-lipoic acid has been used as a cosmetic raw material in some well-known anti-aging and whitening spot-removing products, such as Vifferson, Reviva Labs, Paula's Choice, Hada-Labo (muscular research) and the like, and good market feedback has been obtained. However, the application of lipoic acid still has certain limitations, which are mainly related to the special physical and chemical properties of lipoic acid, and the lipoic acid is represented by extremely weak solubility in water and only 0.08% of soluble mass fraction at normal temperature, which brings inconvenience to the processing and preparation of subsequent products. The lipoic acid is easy to decompose under oxygen and illumination, and has low bioavailability, poor stability and certain irritation. If the application of the lipoic acid in the field of cosmetics is to be fully exerted, the lipoic acid in different dissolved states is needed, mainly because the problems of air pollution and the like cause more dust on the surface of skin and more metal ions contained in sweat, at the moment, the water-soluble lipoic acid is needed to be quickly dissolved on the surface of the skin such as the sweat and the like, and the water-soluble lipoic acid is chelated with the metal ions such as iron, copper, cadmium, lead, mercury and the like and is removed, so that the peroxidation of macromolecules such as lipid and the like caused by the metal ions is reduced; it is also required that the fat-soluble lipoic acid can directly play a role in scavenging free radicals such as hydroxyl free radicals and singlet oxygen after rapidly entering cells, and the capability of endogenous antioxidants such as vitamin E and glutathione is recovered, so that the integral antioxidant capacity of the organism is improved. Therefore, it is important to find a method for solving the problems of water solubility and fat solubility of lipoic acid, improving the existing stability of lipoic acid and reducing irritation.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide the lipoic acid mixed micelle, which greatly improves the water solubility and stability of the lipoic acid and has good clinical value.
The second objective of the present invention is to provide a method for preparing the lipoic acid mixed micelle.
The invention also aims to provide the application of the lipoic acid mixed micelle.
One of the purposes of the invention is realized by adopting the following technical scheme:
a thioctic acid mixed micelle consists of thioctic acid, phospholipid, sodium thioctate and solvent;
the solvent is selected from purified water, sodium chloride aqueous solution, phosphate solution with pH 7.4-8.2.
Further, the addition ratio of the phospholipid to the lipoic acid, the sodium lipoate and the solvent is (2-4) mg: 1 mg: (1-2) mg: (0.1-0.5) mL.
Further, the phospholipid is selected from one of soybean lecithin, egg yolk lecithin, hydrogenated soybean phospholipid, cephalin, inositol phospholipid, serine phospholipid and polyene phosphatidylcholine.
The second purpose of the invention is realized by adopting the following technical scheme:
the preparation method of the lipoic acid mixed micelle comprises the following steps: dissolving lipoic acid and phospholipid in an organic solvent, uniformly dispersing by using ultrasonic waves, and removing the organic solvent to obtain a lipoic acid micelle coprecipitate film; dissolving sodium lipoate in a solvent to obtain a mixed solution, adding the mixed solution into the lipoic acid micelle coprecipitate film for hydration, and performing ultrasonic treatment and filtration to obtain the lipoic acid mixed micelle.
Further, the organic solvent is selected from one or more of ethyl acetate, acetone, chloroform, methanol, ethanol and diethyl ether.
Further, the addition ratio of the phospholipid to the organic solvent is 1 mg: 0.01-0.5 mL.
Furthermore, the aperture of the filter membrane for filtration is 0.22-0.8 μm.
The third purpose of the invention is realized by adopting the following technical scheme:
the lipoic acid mixed micelle can be used in cosmetics or can be prepared into a pharmaceutical composition together with pharmaceutically acceptable pharmaceutic adjuvants.
Furthermore, the lipoic acid mixed micelle is used in cosmetics for whitening, removing freckles and resisting aging, or is used for preparing a pharmaceutical composition with the functions of resisting oxidation, treating cardiovascular diseases, treating acute and chronic inflammations, treating gout and protecting liver with pharmaceutically acceptable pharmaceutic adjuvants.
Further, the final dosage form of the mixture micelle is one of ointment, gel, emulsion, nano preparation, tablet, capsule, granule, suspension and powder injection.
Compared with the prior art, the invention has the beneficial effects that:
the invention provides a lipoic acid mixed micelle which is prepared from lipoic acid, phospholipid and sodium lipoate, has simple components, has stronger stability and can still maintain the property of the micelle after different dilution times and long-term storage. The invention also provides a preparation method of the lipoic acid mixed micelle, the preparation method has simple process and high repeatability, and the used organic solvent can be recycled and is suitable for industrial production. The phospholipid and the sodium lipoate in the mixed micelle have good biocompatibility, and do not need ethanol, propylene glycol and other organic solvents with large stimulation for solubilization, and the obtained mixed micelle has no side effect when in use, is safe and reliable, has wide raw material sources and is low in cost. The mixed micelle contains lipoic acid in different dissolved states, which is mainly because the problems of air pollution and the like cause more dust on the surface of skin and more metal ions contained in sweat, and at the moment, the water-soluble sodium lipoate is required to be quickly dissolved on the surface of the skin such as the sweat and the like, and is chelated with the metal ions such as iron, copper, cadmium, lead, mercury and the like and removed, so that the peroxidation of macromolecules such as lipid and the like caused by the metal ions is reduced; it is also required that the fat-soluble proto-lipoic acid can directly play a role in scavenging free radicals such as hydroxyl free radicals and singlet oxygen after rapidly entering cells, and recover the capabilities of endogenous antioxidants such as vitamin E and glutathione, thereby improving the overall antioxidant capacity of the organism. The invention also provides the application of the lipoic acid mixed micelle, the mixed micelle can be used for preparing cosmetics and pharmaceutical excipients acceptable in pharmacy to prepare a pharmaceutical composition, and the lipoic acid mixed micelle can be used for preparing oral preparations and skin coatings and can be diluted to different degrees for use, thereby greatly facilitating clinical administration.
Detailed Description
The present invention is further described below with reference to specific embodiments, and it should be noted that, without conflict, any combination between the embodiments or technical features described below may form a new embodiment.
Example 1
A lipoic acid mixed micelle, which comprises the following steps:
150mg of soybean lecithin and 50mg of lipoic acid are weighed and placed in a 50mL round-bottom flask, 10mL of methanol is added into the flask for dissolution, and the mixture is uniformly dispersed by ultrasonic. Removing methanol by rotary evaporation at the water bath temperature of 40 ℃ to form a layer of transparent lipoic acid micelle coprecipitate film, dissolving 50mg of sodium lipoate in 10mL of purified water to obtain a mixed solution, adding the mixed solution into the transparent film to hydrate the film to obtain a dispersion solution containing the medicine mixed micelle, performing probe ultrasonic treatment (50W, at an interval of 2s for 2min), filtering by using a 0.22 mu m microporous filter membrane, taking the filtrate, and subpackaging to obtain the lipoic acid mixed micelle.
Example 2
A lipoic acid mixed micelle, which comprises the following steps:
150mg of soybean lecithin and 50mg of lipoic acid are weighed and placed in a 50mL round-bottom flask, 10mL of dichloromethane is added to the soybean lecithin and dissolved, and the soybean lecithin and the lipoic acid are uniformly dispersed by ultrasound. Removing dichloromethane by rotary evaporation at the water bath temperature of 35 ℃ to form a layer of transparent lipoic acid micelle coprecipitate film, dissolving 50mg of sodium lipoate in 10mL of purified water to obtain a mixed solution, adding the mixed solution into the transparent film to hydrate the film to obtain a dispersion solution containing the medicine mixed micelle, performing probe ultrasonic treatment (50W, at an interval of 2s for 2min), filtering with a 0.22 mu m microporous filter membrane, taking the filtrate, and subpackaging to obtain the lipoic acid mixed micelle.
Example 3
A lipoic acid mixed micelle, which comprises the following steps:
150mg of soybean lecithin and 50mg of lipoic acid are weighed and placed in a 50mL round-bottom flask, 10mL of ethanol is added into the flask for dissolution, and the mixture is uniformly dispersed by ultrasonic. Removing ethanol by rotary evaporation at the water bath temperature of 45 ℃ to form a layer of transparent lipoic acid micelle coprecipitate film, dissolving 100mg of sodium lipoate in 10mL of purified water to obtain a mixed solution, adding the mixed solution into the transparent film to hydrate the film to obtain a dispersion solution containing the medicine mixed micelle, performing probe ultrasonic treatment (50W, at an interval of 2s for 2min), filtering by using a 0.22 mu m microporous filter membrane, taking the filtrate, and subpackaging to obtain the lipoic acid mixed micelle.
Example 4
A lipoic acid mixed micelle, which comprises the following steps:
150mg of egg yolk lecithin and 50mg of lipoic acid are weighed and placed in a 50mL round-bottom flask, 10mL of methanol is added into the round-bottom flask for dissolution, and the mixture is uniformly dispersed by ultrasonic. Removing methanol by rotary evaporation at the water bath temperature of 45 ℃ to form a layer of transparent lipoic acid micelle coprecipitate film, dissolving 100mg of sodium lipoate in 10mL of purified water to obtain a mixed solution, adding the mixed solution into the transparent film to hydrate the film to obtain a dispersion solution containing the medicine mixed micelle, performing probe ultrasonic treatment (50W, at an interval of 2s for 2min), filtering by using a 0.22 mu m microporous filter membrane, taking the filtrate, and subpackaging to obtain the lipoic acid mixed micelle.
Example 5
A lipoic acid mixed micelle, which comprises the following steps:
150mg of egg yolk lecithin and 50mg of lipoic acid are weighed and placed in a 50mL round-bottom flask, 10mL of ethanol is added into the round-bottom flask for dissolution, and the mixture is uniformly dispersed by ultrasonic. Removing ethanol by rotary evaporation at the water bath temperature of 45 ℃ until no ethanol smell exists, forming a layer of transparent lipoic acid micelle coprecipitate film, dissolving 50mg of sodium lipoate in 10mL of purified water to obtain a mixed solution, adding the mixed solution into the transparent film to hydrate the film to obtain a dispersion solution containing the medicine mixed micelle, performing probe ultrasonic treatment (50W, at an interval of 2s for 2min), filtering by using a 0.22 mu m microporous filter membrane, taking a filtrate, and subpackaging to obtain the lipoic acid mixed micelle.
Example 6
The preparation process of lipoic acid mixed micelle includes the following steps:
150mg of soybean lecithin and 50mg of lipoic acid are weighed and placed in a 50mL round-bottom flask, 10mL of dichloromethane is added to the soybean lecithin and dissolved, and the soybean lecithin and the lipoic acid are uniformly dispersed by ultrasound. Removing dichloromethane by rotary evaporation at the water bath temperature of 35 ℃ to form a layer of transparent lipoic acid micelle coprecipitate film, dissolving 50mg of sodium lipoate in 10mL of purified water to obtain a mixed solution, adding the mixed solution into the transparent film to hydrate the film to obtain a dispersion solution containing the medicine mixed micelle, performing probe ultrasonic treatment (50W, at an interval of 2s for 2min), filtering with a 0.22 mu m microporous filter membrane, taking the filtrate, and subpackaging to obtain the lipoic acid mixed micelle.
Example 7
A lipoic acid mixed micelle, which comprises the following steps:
150mg of polyene phosphatidyl choline and 50mg of lipoic acid are weighed and placed in a 50mL round-bottom flask, 10mL of diethyl ether is added to the round-bottom flask for dissolving, and the mixture is uniformly dispersed by ultrasonic. Removing ether by rotary evaporation at the water bath temperature of 35 ℃ to form a layer of transparent lipoic acid micelle coprecipitate film, dissolving 50mg of sodium lipoate in 10mL of phosphate aqueous solution with the pH value of 7.4 to obtain a mixed solution, adding the mixed solution into the transparent film to hydrate the film to obtain a dispersion solution containing the medicine mixed micelle, performing probe ultrasonic treatment (50W, at the interval of 2s for 2min), filtering by using a 0.22 mu m microporous filter membrane, taking the filtrate, and subpackaging to obtain the lipoic acid mixed micelle.
Example 8
A lipoic acid mixed micelle, which comprises the following steps:
150mg of hydrogenated soybean phospholipid and 50mg of lipoic acid are weighed and placed in a 50mL round-bottom flask, 10mL of ethanol is added into the round-bottom flask for dissolution, and the mixture is uniformly dispersed by ultrasonic. Removing ethanol by rotary evaporation at the water bath temperature of 45 ℃ to form a layer of transparent lipoic acid micelle coprecipitate film, dissolving 50mg of sodium lipoate in 10mL of purified water to obtain a mixed solution, adding the mixed solution into the transparent film to hydrate the film to obtain a dispersion solution containing the medicine mixed micelle, performing probe ultrasonic treatment (50W, at an interval of 2s for 2min), filtering by using a 0.22 mu m microporous filter membrane, taking the filtrate, and subpackaging to obtain the lipoic acid mixed micelle.
Comparative example 1
Comparative example 1 differs from example 3 in that: the sodium lipoate was omitted and the same procedure as in example 3 was repeated to obtain a lipoic acid mixed micelle.
Experimental example 1
The lipoic acid mixed micelles of examples 1 to 8 and comparative example 1 were examined for particle size, Zeta potential, and distribution coefficient (PDI) using a malvern ZS-90 nm particle sizer, and the results are shown in table 1:
TABLE 1
Figure BDA0003426203780000051
As can be seen from Table 1, the particle size of the lipoic acid mixed micelles obtained in the examples 1 to 8 of the invention is within the range of 61.1-101.7nm, the zeta potential is-17.3 to-28.1 mV, and the PDI is between 0.162 and 0.231, so that the lipoic acid micelles are suitable for being prepared into a suspension or a powder injection. Compared with the embodiment 3, the sodium lipoate in the comparative example 1 is omitted, and the obtained lipoic acid mixed micelle has smaller particle size, lower zeta potential and larger PDI, which is not beneficial to the later preparation of various pharmaceutical dosage forms.
Experimental example 2
Stability test
2.1 dilution stability test
The lipoic acid mixed micelles obtained in examples 1 to 8 of the present invention and comparative example 1 were diluted with 1, 3 and 5 times of purified water, respectively, and the stability of the lipoic acid mixed micelles was observed after dilution by different times, and the results are shown in table 2. The result shows that the appearance of the lipoic acid mixed micelle after dilution by different times shows a light yellow transparent solution, has opalescence, does not precipitate and shows good stability. Compared with the lipoic acid mixed micelles obtained in example 3, the lipoic acid mixed micelles obtained in comparative example 1 have no obvious difference when diluted by 1 time, but when diluted by 3 times or 5 times, the diluted micelles cannot exist stably, and the phenomena of micelle instability such as flocculation, delamination and the like gradually occur.
TABLE 2
Figure BDA0003426203780000061
2.2 Long term stability testing
The lipoic acid mixed micelles obtained in examples 1 to 8 and comparative example 1 were left to stand in a refrigerator at 4 ℃ for 0 to 3 months to examine their long-term stability, and the results are shown in table 3. It is understood from the table that the appearance of the micelles prepared in the examples is a light yellow transparent solution, which has opalescence, and no precipitate is precipitated after standing for 3 months, thus showing good stability. The appearance of the freshly prepared lipoic acid mixed micelles obtained in comparative example 1 is not obviously different from that of example 3, but the lipoic acid mixed micelles in comparative example 1 gradually show flocculation and delamination phenomena when the lipoic acid mixed micelles are respectively kept for 1 month and 3 months under the same test conditions, and it is known that the omission of sodium lipoate reduces the stability of the lipoic acid mixed micelles.
TABLE 3
Figure BDA0003426203780000071
Figure BDA0003426203780000081
Experimental example 3
Detection of DPPH free radical scavenging capability of lipoic acid mixed micelle
The lipoic acid mixed micelles obtained in examples 1 to 8 and comparative example 1 of the invention are respectively diluted by 10 times to obtain the solution to be tested. 20mg of DPPH is dissolved in 250mL of ethanol and stored at 0-4 ℃ in the dark. 3mL of DPPH ethanol solution was added to each tube, an equal volume of water (A1) was added to the control tube, an equal volume of example test solution (A2) was added to the sample tube, and 3mL of water and an equal volume of example test solution (A3) were added to the blank control tube. After 30min of reaction, the absorbance of each tube was measured at 517nm and the DPPH radical clearance was calculated. The DPPH radical clearance metric was calculated as follows, and the results are shown in table 4.
Figure BDA0003426203780000082
TABLE 4
Figure BDA0003426203780000083
As can be seen from Table 4, the thioctic acid mixed micelles obtained in examples 1 to 8 of the present invention have DPPH radical scavenging rate of 21.11-44.18%. It can be known that the lipoic acid mixed micelle prepared by the invention does not negatively influence the free radical scavenging capability of the lipoic acid. In contrast, in comparative example 1, the DPPH radical scavenging rate was only 17.18% as compared to example 3, and it is known that the omission of sodium lipoate did not allow the lipoic acid to fully and effectively exert its radical scavenging function in the lipoic acid mixed micelles.
Experimental example 4
Detection of effects on inflammatory factor Release levels
Taking HaCat cells (human immortalized epidermal cells) in logarithmic growth phase at 2X 106Inoculating the cell turbid solution on a 6-hole cell culture plate at the density of each/mL, adding 1mL of cell suspension into each hole, culturing for 24h in an incubator, and carefully sucking the supernatant; adding 1mL of DMEM solution into the blank group and the model group respectively; the test solution added in the example 3 group was 1000 times diluted the lipoic acid mixed micelles prepared in example 3, and the lipoic acid mixed micelles prepared in comparative example 1 added in the comparative example 1 in the same ratio as in the example 3 group. After adding, continuing culturing for 6h, and irradiating the model group, the group of example 3 and the group of comparative example 1 by ultraviolet light with the illumination power of 9J/cm2The irradiation time was 1.5h, and the blank control group was not irradiated with light. Incubation was continued for 24h after illumination and each set of samples was repeated 3 replicates and each replicate was tested 3 times. And (3) treating cells, collecting cell lysate, centrifuging at 10000r/min for 10min to obtain cell lysis supernatant, and taking 20 mu L of cell lysis supernatant and using a BCA kit to detect the total protein content in a sample. The release levels of the IL-1. alpha. inflammatory factor in the blank control group, the model group, the example 3 group and the comparative example 1 group were measured, respectively, and after performing experimental procedures according to the ELISA kit instructions, each OD value was measured at 450nm, and the release level of the IL-1. alpha. inflammatory factor was calculated from the OD values, and the results are shown in Table 5:
TABLE 5
Figure BDA0003426203780000091
As can be seen from the table, the lipoic acid mixed micelles added in example 3 group showed stronger inhibition of IL-1 α validation factor level release than the model group, blank group and comparative example 1 group, and the expression level was only 0.87 ng/L. The character of the lipoic acid mixed micelle prepared by the invention does not influence the property of the lipoic acid.
In conclusion, the lipoic acid mixed micelle is prepared from lipoic acid, phospholipid and sodium lipoate, and has simple components and high drug loading. The obtained lipoic acid mixed micelle has stronger stability, can still keep better stability after being diluted by 5 times and stored for a long time, and does not precipitate crystals and other precipitates. The phospholipid and the sodium lipoate in the mixed micelle have good biocompatibility, do not need ethanol, propylene glycol and other organic solvents with large stimulation for solubilization, reduce the toxicity of medicaments and cosmetics prepared in the later period, have small irritation to blood vessels and skin, and are beneficial to reducing the adverse reaction of users on the medicaments or the cosmetics. The thioctic acid mixed micelle prepared by the invention has no influence on the scavenging action of free radicals and the release level of inflammatory factors, and has no limit or other negative influences on the properties of the thioctic acid. When the lipoic acid mixed micelle is used for preparing the pharmaceutical composition, the lipoic acid mixed micelle can be used for preparing oral preparations, skin coating and the like, and can be diluted to different degrees for use, thereby greatly facilitating clinical administration.
The above embodiments are only preferred embodiments of the present invention, and the protection scope of the present invention is not limited thereby, and any insubstantial changes and substitutions made by those skilled in the art based on the present invention are within the protection scope of the present invention.

Claims (10)

1. The lipoic acid mixed micelle is characterized by consisting of lipoic acid, phospholipid, sodium lipoate and a solvent;
the solvent is selected from one of purified water, sodium chloride aqueous solution and phosphate solution with pH of 7.4-8.2.
2. The lipoic acid mixed micelle of claim 1, wherein the phospholipid is added in a ratio of (0.1-4) mg: 1 mg: (0.5-2) mg: (0.1-0.5) mL.
3. The lipoic acid mixed micelle of claim 1, wherein the phospholipid is selected from the group consisting of soybean lecithin, egg yolk lecithin, hydrogenated soybean lecithin, cephalin, inositol phosphatides, serine phosphatides, and polyenylphosphatidylcholine.
4. The method of preparing lipoic acid mixed micelles of any of claims 1 to 3, comprising the following steps: dissolving lipoic acid and phospholipid in an organic solvent, uniformly dispersing by using ultrasonic waves, and removing the organic solvent to obtain a lipoic acid micelle coprecipitate film; dissolving sodium lipoate in a solvent to obtain a mixed solution, adding the mixed solution into the lipoic acid micelle coprecipitate film for hydration, and performing ultrasonic treatment and filtration to obtain the lipoic acid mixed micelle.
5. The method of preparing lipoic acid mixed micelles of claim 4, wherein said organic solvent is selected from one or more of ethyl acetate, acetone, chloroform, methanol, ethanol, and diethyl ether.
6. The method of preparing lipoic acid mixed micelles of claim 5, wherein the addition ratio of phospholipids to organic solvent is 1 mg: 0.01-0.5 mL.
7. The method of claim 6, wherein the filter membrane has a pore size of 0.22-0.8 μm.
8. Use of lipoic acid mixed micelles according to any of the claims 1 to 3, characterised in that the lipoic acid mixed micelles can be used in cosmetics or with pharmaceutically acceptable pharmaceutical excipients to prepare pharmaceutical compositions.
9. The use of the lipoic acid mixed micelle of claim 8, in the cosmetics for whitening skin, removing freckles and resisting aging, or in the preparation of pharmaceutical compositions with antioxidant, cardiovascular disease treatment, acute and chronic inflammation treatment, gout treatment and liver protection with pharmaceutically acceptable pharmaceutical excipients.
10. The use of lipoic acid mixed micelles of claim 9, wherein the final formulation of said mixed micelles is one of an ointment, a gel, an emulsion, a nano-formulation, a tablet, a capsule, a granule, a suspension, and a powder injection.
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