Lithospermum erythrorhizon extract nanometer microcrystal particle, self-microemulsion thereof, preparation method and application thereof

Abstract

The invention provides a lithospermum erythrorhizon extract nano microcrystal particle. The lithospermum erythrorhizon extract nano microcrystal particle is prepared from 5 to 100 parts of lithospermum erythrorhizon naphthoquinone active ingredient extract, 1 to 100 parts of ionic cellulose gum, 1 to 100 parts of chitosan, 5 to 100 parts of polylactic acid and 5 to 100 parts of sodium alginate. The invention also provides a preparation method of the lithospermum erythrorhizon extract nano-microcrystal particles, a self-microemulsion containing the lithospermum erythrorhizon extract nano-microcrystals, and a preparation method and application of the self-microemulsion. According to the lithospermum erythrorhizon extract nano-microcrystal particles and the self-microemulsion system prepared from the lithospermum erythrorhizon extract nano-microcrystal particles, the stability of the lithospermum erythrorhizon extract can be improved, the problem that the lithospermum erythrorhizon extract is insoluble in water is solved, the solubility and the absorptivity of the lithospermum erythrorhizon extract are improved, and the biological activity of the lithospermum erythrorhizon extract nano-microcrystal particles is improved.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical preparations, and in particular to lithospermum officinale extract nano-microcrystalline particles and self-microemulsification thereof, a preparation method and application thereof. Background Art

[0002] Lithospermum officinale is a perennial herbaceous plant of the Boraginaceae family, mainly distributed throughout my country, and also distributed in some other countries or regions. There are two main sources of Lithospermum officinale, the pseudo-Boraginaceae plant Xinjiang Lithospermum officinale (also known as soft lithospermum officinale) (Arnebeia euchromaRoyle Johnst) and the Lithospermum officinale plant Lithospermum officinale (also known as hard lithospermum officinale) (Lithospermumery throrhizonS etZ). Lithospermum officinale has a long history of medicinal use in my country. The Compendium of Materia Medica says: "Lithospermum officinale treats blood circulation, cooling blood, macules, pox, and benefits the large intestine." It tastes sweet and salty, is cold in nature, and is in the pericardium and liver meridians, and has the effects of cooling blood, activating blood circulation, clearing heat, and detoxifying. It is mainly used in clinical Chinese medicine for diseases such as wet macules, purple epilepsy, hematuria, eczema, stranguria and bloody dysentery, constipation due to heat, erysipelas, burns, and carbuncles. Lithospermum officinale contains a variety of chemical components, including naphthoquinones, benzoquinones, alkaloids, phenols, phenolic acids, triterpene acids, sterols, flavonoids and polysaccharides.

[0003] Natural shikonin exists in lithospermum mainly in the form of acyl derivatives, including acetyl shikonin, β, β-dimethyl acryloyl shikonin, isovaleryl shikonin, isobutyryl shikonin, etc., among which β, β-dimethyl acryloyl shikonin has the highest content. As a natural active ingredient of traditional Chinese medicine, it has good antibacterial, anti-tumor, antioxidant, antiviral, anti-inflammatory and promotes the healing of burn wounds. Shikonin itself is easily affected by external factors such as light and heat, is unstable when used, is easily oxidized by air, and has poor water solubility, which limits the development of its preparations.

[0004] By designing a suitable sustained-release and controlled-release system, the stability, solubility and absorption rate of Lithospermum officinale extract can be improved, and its activity and application can be better exerted. The solid self-microemulsifying drug delivery system is a solid system composed of an oil phase, an emulsifier, an emulsifying solvent, and a solid adsorbent. The free energy required for emulsification is very low. It spontaneously forms emulsions in a 37°C water bath in vitro, under gentle stirring, or under the peristalsis of the stomach and intestines in vivo, forming tiny droplets (particle size ≤ 5μm). It uses its huge specific surface area to greatly improve the bioavailability of such drugs, and can also overcome the shortcomings of ordinary emulsions such as large volume of administration and difficulty in controlling its stability. At the same time, it can avoid the hydrolysis of water-unstable drugs and adverse stimulation of drugs to the stomach and intestines. The solid self-microemulsifying drug delivery system is a solid preparation prepared by mixing the self-microemulsifying components with suitable solid materials or by other technologies, including self-microemulsifying microcapsules, microspheres and tablets. Compared with the traditional self-microemulsification system, it has the advantages of increased stability, extended storage time, reduced irritation, and easy administration. It can also be conveniently used to prepare sustained-release preparations by adding various solid excipients or using coating technology. It is a new type of preparation with great development prospects for poorly soluble drugs. Summary of the invention

[0005] In order to solve the above technical problems, the present invention provides a lithospermum extract nano-microcrystalline particle and a self-microemulsion system prepared therefrom, which can improve the stability of the lithospermum extract, solve the property that the lithospermum extract is difficult to dissolve in water, improve the solubility and absorption rate of the lithospermum extract, and are conducive to the improvement of its biological activity, including antibacterial, anti-inflammatory, anti-cancer, treatment and prevention of skin infection diseases such as acute and chronic hepatitis, cirrhosis (ascites), treatment of flat warts and psoriasis, local application treatment of burns and promotion of wound healing, treatment of infant dermatitis, eczema, vaginitis, cervicitis, and the like, and can also be used to improve human skin conditions, repair damage, promote cell metabolism, anti-inflammatory, whiten skin, etc.

[0006] Specifically, the present invention provides a lithospermum extract nano-microcrystalline particles, comprising: 5-100 parts of lithospermum naphthoquinone active ingredient extract, 1-100 parts of ionic cellulose gum, 1-100 parts of chitosan, 5-100 parts of polylactic acid, and 5-100 parts of sodium alginate.

[0007] In some embodiments, the ionic cellulose gum is a carboxymethylated cellulose, such as sodium carboxymethyl cellulose (CMC-Na).

[0008] In addition, the present invention also provides a method for preparing nano-microcrystalline particles of lithospermum extract, comprising hydrothermally complexing the lithospermum naphthoquinone active ingredient extract with ionic cellulose gum, chitosan oligosaccharide, polylactic acid, and sodium alginate to form nano-microcrystalline particles;

[0009] Among them, 5-100 parts of lithospermum naphthoquinone active ingredient extract, 1-100 parts of ionic cellulose gum, 1-100 parts of chitosan, 5-100 parts of polylactic acid, and 5-100 parts of sodium alginate.

[0010] In some embodiments, the method for preparing the lithospermum extract nano-microcrystalline particles comprises hydrothermally synthesizing the lithospermum naphthoquinone active ingredient extract and the tissue compatible material at a molar ratio of 1:1 at 60-90° C. to form nano-microcrystalline particles.

[0011] The tissue compatible materials include ionic cellulose gum, chitosan, polylactic acid and sodium alginate.

[0012] In addition, the present invention also provides a self-microemulsion of lithospermum extract nanocrystals, comprising: 10-150 parts of lithospermum extract nanocrystals, 10-25 parts of oil phase, 10-30 parts of surfactant, 2-15 parts of co-surfactant and 5-20 parts of solid absorbent.

[0013] In some embodiments, the lithospermum extract nanocrystals include: 5-100 parts of lithospermum naphthoquinone active ingredient extract, 1-100 parts of ionic cellulose gum, 1-100 parts of chitosan, 5-100 parts of polylactic acid, and 5-100 parts of sodium alginate.

[0014] In some embodiments, the oil phase is any one or a combination of grape seed oil, evening primrose oil, Capmul MCM, ethyl oleate, sunflower oil, Capryol 90, coconut oil, corn oil, and castor oil.

[0015] In some embodiments, the surfactant is any one or a combination of cetearyl alcohol and sorbitan olivate, Cremophor EL, Solutol HS, Tween-(20, 60, 80), decaglycerol monolaurate, caprylic / capric macrogol glyceride, polyoxyacetic stearic acid, and Labrasol.

[0016] In some embodiments, the co-surfactant is any one or a combination of ethanol, PEG-400, PEG-600, polyglycerol ricinoleate, cetyl polyethylene glycol / polypropylene glycol, polyethylene glycol-dipolyhydroxystearate, and Transcutol P.

[0017] In some embodiments, the solid adsorbent is any one or a combination of gum arabic, isopropyl citrate, anhydrous calcium carbonate, magnesium aluminum silicate, silicon dioxide, and mannitol.

[0018] In addition, the present invention also provides a method for preparing self-microemulsion of lithospermum officinale extract nanocrystals, comprising:

[0019] (1) using hydrothermal complexation to form nano-crystal particles by combining lithospermum erythrorhizon extract with ionic cellulose gum, polylactic acid, sodium alginate and chitosan oligosaccharide;

[0020] (2) adding the lithospermum erythrorhizon extract nano-crystal particles obtained in step (1) into the oil phase and stirring and dissolving them to form an oil phase system;

[0021] (3) mixing and stirring the surfactant and the co-surfactant at a constant temperature of 60-80° C., and adding the mixture to the oil phase system obtained in step (2) to obtain a liquid self-microemulsion;

[0022] (4) At room temperature, a solid adsorbent is added to the liquid microemulsion system obtained in step (3) to obtain a solid self-microemulsion.

[0023] In addition, the present invention also provides a composition, comprising the lithospermum extract nano-microcrystalline particles described in the present invention, or comprising the lithospermum extract nano-microcrystalline particles prepared by the method described in the present invention, or comprising the self-microemulsion of the lithospermum extract nano-microcrystals described in the present invention, or comprising the self-microemulsion of the lithospermum extract nano-microcrystals prepared by the method described in the present invention.

[0024] In some embodiments, the composition is a tablet, a capsule, a soft capsule, a granule, a disintegrant, a dispersant, a pill, a micropellet, an oral liquid, a gel, a thermosensitive hydrogel, an ointment, a spray, a tincture, a patch, a film, a medical gauze, a medical tape bandage, a medical implant, a facial mask, a tissue, a care product, an oral care product, or a sustained-release agent.

[0025] In addition, the present invention also provides the lithospermum extract nano-microcrystalline particles of the present invention, or the lithospermum extract nano-microcrystalline particles prepared by the method of the present invention, or the self-microemulsion of the lithospermum extract nano-microcrystalline of the present invention, or the self-microemulsion of the lithospermum extract nano-microcrystalline prepared by the method of the present invention, or the use of the composition of the present invention in preparing drugs, wherein the drugs are used for antibacterial, anti-inflammatory, anti-cancer, treatment and prevention of skin infections; preferably, the drugs are used for treating flat warts and psoriasis, topically treating burns and promoting wound healing, treating infant dermatitis, eczema, vaginitis, and cervicitis, and can also be used to improve human skin conditions, repair damage, promote cell metabolism, and resist inflammation and whiten the skin.

[0026] Beneficial Effects

[0027] The lithospermum extract nano-microcrystalline particles and the self-microemulsion system prepared therefrom of the present invention can improve the stability of the lithospermum extract, solve the problem that the lithospermum extract is poorly soluble in water, improve the solubility and absorption rate of the lithospermum extract, and are beneficial to the improvement of its biological activity, including antibacterial, anti-inflammatory, anti-cancer, treatment and prevention of skin infection diseases such as acute and chronic hepatitis, liver cirrhosis (ascites), treatment of flat warts and psoriasis, local application treatment of burns and promotion of wound healing, treatment of infant dermatitis, eczema, vaginitis and cervicitis, and can also be used to improve human skin conditions, repair damage, promote cell metabolism, anti-inflammatory, whiten skin, etc.

[0028] Terminology

[0029] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.

[0030] The term "wt%" means percentage by mass. The parts used in the present invention are parts by weight based on mass.

[0031] In the following, all numbers disclosed herein are approximate, regardless of whether the word "about" or "approximately" is used. The value of each number may vary by 1%, 2%, 5%, 7%, 8%, 10%, 15% or 20%. Whenever a number with a value of N is disclosed, any number with a value of N+ / -1%, N+ / -2%, N+ / -3%, N+ / -5%, N+ / -7%, N+ / -8%, N+ / -10%, N+ / -15% or N+ / -20% will be explicitly disclosed, where "+ / -" means plus or minus.

[0032] The oil phase of the lithospermum extract nano-microcrystal self-microemulsion is any one of grape seed oil, evening primrose oil, Capmul MCM, ethyl oleate, sunflower oil, Capryol 90, coconut oil, corn oil, and castor oil, or a combination thereof. The surfactant is any one of cetearyl alcohol and sorbitan olive oil ester, Cremophor EL, Solutol HS, Tween-(20, 60, 80), ten polyglycerol monolaurate, caprylic acid / capric acid polyethylene glycol glyceride, polyoxyacetic acid stearic acid, and Labrasol, or a combination thereof. The auxiliary surfactant is any one of ethanol, PEG-400, PEG-600, polyglycerol castor alcohol ester, cetyl polyethylene glycol / polypropylene glycol, polyethylene glycol-dipolyhydroxystearate, and Transcutol P, or a combination thereof. The solid adsorbent is any one of gum arabic, isopropyl citrate, anhydrous calcium carbonate, magnesium aluminum silicate, silicon dioxide, and mannitol, or a combination thereof. DETAILED DESCRIPTION

[0033] In order to enable those skilled in the art to better understand the technical solution of the present invention, some non-limiting embodiments are further disclosed below to further describe the present invention in detail.

[0034] The reagents used in the present invention can be purchased from the market or prepared by the method described in the present invention.

[0035] The present invention investigates the effects of different mass ratios of mixed surfactants, different oil phases, different co-surfactants, different adsorbents and lithospermum extract nanocrystals on the self-emulsification formation, and determines a better self-microemulsification system. The process is as follows:

[0036] Based on the determination of the saturated solubility of lithospermum extract nanocrystals in various media, two optimal mixed surfactants were preliminarily determined through the compatibility test of oil phase and surfactant and the ability of cosolvent to solubilize surfactant. In the process of screening the self-microemulsification system of lithospermum extract nanocrystals, a series of blank self-microemulsification drug delivery systems were prepared by drawing a pseudo-ternary phase diagram and using different concentrations of oil phase, surfactant and co-surfactant.

[0037] Based on the solubility study and pseudo-ternary phase diagram experimental results, the self-microemulsification preparation with the best ratio was selected as the investigation object, the oil phase, surfactant and co-surfactant were weighed according to the optimal prescription, the mixture was vortexed to obtain a clear and uniform solution, the precisely weighed lithospermum extract nanocrystals were added to the above-mentioned blank self-microemulsification drug release system and stirred to dissolve, and a solid adsorbent was added to prepare a nanocrystal self-microemulsification drug release system of lithospermum extract.

[0038] The self-emulsification ratio of lithospermum extract nanocrystals was finally determined based on the size of the self-emulsification region in the phase diagram, the lowest eutectic point of the system, the self-emulsification particle size and the self-emulsification efficiency as evaluation indicators.

[0039] Example 1, preparation of Lithospermum officinale extract

[0040] Lithospermum officinale extract is a naphthoquinone extract, which is obtained by alcohol extraction using lithospermum officinale as raw material:

[0041] The lithospermum officinale was crushed and dried, poured into a percolation tank, and 95% ethanol was poured into it at a solid-liquid ratio of 1:8 (w / v). After standing at room temperature (25 degrees) for 24 hours, the filtrate was released. The filter residue was poured into ethanol at a solid-liquid ratio of 1:6 (w / v), and the filtrate was released after 24 hours. The filter residue was added with ethanol at a solid-liquid ratio of 1:4 (w / v) to continue extraction, and the filtrate was released after 24 hours. The three percolations were combined, and vacuum distilled at 90 degrees, and concentrated until no solution dripped out of the receiving tank, and the concentrated solution was poured out, and the residual solvent was evaporated to obtain the lithospermum officinale naphthoquinone extract.

[0042] Example 2: Preparation of Lithospermum officinale extract nanocrystalline particles

[0043] Hydrothermal Synthesis of Nanocrystals of Lithospermum officinale Extract

[0044] The lithospermum extract and polylactic acid were added into 10 times amount of water in a molar ratio of 1:1, and the mixture was subjected to hydrothermal synthesis at 90° C. for 4 hours to obtain lithospermum extract-lactic acid nanocrystal solid powder.

[0045] Example 3: Preparation of Lithospermum officinale extract self-microemulsion

[0046] The lithospermum extract is added into the oil phase and stirred to dissolve to form an oil phase system; the surfactant and the co-surfactant are mixed and stirred at a constant temperature of 60-70 DEG C, and added into the oil phase to obtain a liquid self-microemulsion; after the self-microemulsion of the lithospermum extract is sterilized, a solid adsorbent is added into the self-microemulsion system at room temperature to obtain a solid self-microemulsion.

[0047] Example 4: Preparation of Lithospermum officinale extract preparation

[0048] Example 4-1, Lithospermum officinale extract-lactic acid nano-microchip preparation

[0049] Dissolve sodium carboxymethyl cellulose in an appropriate amount of distilled water and stir until it is colloid. Weigh the prescribed amount of lithospermum extract-lactic acid nanocrystals and starch, mix them, add sodium carboxymethyl cellulose solution to prepare a soft material, sieve the prepared soft material by extrusion, and then dry it in an oven at 30°C. Sieve the dried particles and add sodium carboxymethyl starch to mix, then add talcum powder and mix evenly, and manually press the tablets with a tablet press to prepare lithospermum extract tablets.

[0050] prescription:

[0051]

[0052] Example 4-2 Lithospermum officinale extract-lactic acid nanocrystal soft capsule

[0053] Lithospermum extract-lactic acid nanocrystals are added to refined edible vegetable oil, dissolved by ultrasonic, and sterilized to form soft capsules. Each soft capsule contains 50 mg of lithospermum extract.

[0054] The soft capsule preparation code is: RA-2.

[0055] Soft capsule preparation process:

[0056] (1) Gelatinization: Weigh gelatin: glycerol: purified water in a ratio of 1:0.3:1. After the gelatin is fully swollen, add the remaining purified water and glycerol and mix them. Place the mixture in a gelatinization tank and heat it to 70°C. Stir for 20 minutes. Add 0.2% potassium sorbate to the total amount. Vacuum the gelatin to remove all air from the gelatin and set aside.

[0057] (2) Pill pressing: Heat the gelatin box to 50°C, control the pressure in the gelatin tank to be no more than 0.04 MPa, and maintain the temperature between 80 and 90°C to press the gelatin film. Press the qualified gelatin film and lithospermum extract solution into soft capsules through a fully automatic soft capsule machine.

[0058] (3) The pills are shaped, dried, polished and inspected, and the qualified soft capsules are placed in a clean and dry container.

[0059] Example 4-3 Lithospermum officinale extract-lactic acid nanocrystal self-microemulsion nanoparticles

[0060] The lithospermum extract is added into the oil phase and stirred to dissolve to form an oil phase system; a surfactant and a co-surfactant are mixed and stirred at a constant temperature of 60-70 DEG C, and added into the oil phase to obtain a liquid self-microemulsion; after the self-microemulsion of the lithospermum extract is sterilized, a solid adsorbent is added into the self-microemulsion system at room temperature to obtain a solid self-microemulsion, which is dried and ultrafinely pulverized to prepare nanoparticles.

[0061] Each solid self-microemulsifying granule contains 50 mg of lithospermum officinale extract.

[0062] The optimal ratio of oil phase, surfactant, co-surfactant and solid adsorbent:

[0063] Capryol 90 as oil phase: Tween-60 as surfactant: PEG-400 as co-surfactant: gum arabic as adsorbent = 1:1.3:1.8:1.6.

[0064] The granule codes of nano-microcrystalline self-microemulsification are: SSMEDDS-RA-1.

[0065] Example 4-4 Lithospermum officinale extract-lactic acid nanocrystal self-microemulsion gel

[0066] The lithospermum extract-lactic acid nanocrystals are added to the oil phase and stirred to dissolve to form an oil phase system; the surfactant and the co-surfactant are mixed and stirred at a constant temperature of 60-70°C, and added to the oil phase to obtain a liquid self-microemulsion; after the lithospermum extract self-microemulsion is sterilized, a solid adsorbent is added to the self-microemulsion system at room temperature to obtain a solid self-microemulsion.

[0067] The optimal ratio of oil phase, surfactant, co-surfactant and solid adsorbent:

[0068] Capmul MCM as oil phase: Tween-40 as surfactant: Transcutol P as co-surfactant: isopropyl citrate as adsorbent = 1:1.4:2.1:1.6.

[0069] Take carbomer 940, glycerin, polysorbate 80 and mix them with 300 ml of distilled water, dissolve sodium hydroxide in 100 ml of distilled water and add it to the above liquid and stir, then gradually add the lithospermum extract nano-microcrystalline solid self-microemulsion and stir well to obtain a transparent gel.

[0070] Nano-microcrystalline self-microemulsification gel contains lithospermum officinale extract: 10 mg / g.

[0071] The capsule preparation codes of nano-microcrystal self-microemulsion are: SSMEDDS-RA-2.

[0072] Example 5, property test

[0073] The properties of the preparations obtained in Examples 4-3 and 4-4 were tested, and the test results are shown in Table 1:

[0074] Table 1:

[0075]

[0076] The method of the present invention has been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the methods and applications described herein within the content, spirit and scope of the present invention to implement and apply the technology of the present invention. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters. It is particularly important to point out that all similar replacements and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention.

Claims

1. A lithospermum officinale extract nano-microcrystalline particle, comprising: 5-100 parts of lithonaquinone active ingredient extract, 1-100 parts of ionic cellulose gum, 1-100 parts of chitosan, 5-100 parts of polylactic acid and 5-100 parts of sodium alginate.

2. The lithospermum extract nano-microcrystalline particles according to claim 1, characterized in that: The ionic cellulose gum is a carboxymethylated product of cellulose, such as sodium carboxymethyl cellulose (CMC-Na).

3. A method for preparing nano-microcrystalline particles of lithospermum officinale extract, comprising hydrothermally complexing the lithospermum officinale naphthoquinone active ingredient extract with ionic cellulose gum, chitosan oligosaccharide, polylactic acid, and sodium alginate to form nano-microcrystalline particles; in, 5-100 parts of lithonaquinone active ingredient extract, 1-100 parts of ionic cellulose gum, 1-100 parts of chitosan, 5-100 parts of polylactic acid and 5-100 parts of sodium alginate.

4. The method for preparing nano-crystal particles of Lithospermum officinale extract according to claim 3, characterized in that: The active ingredient extract of lithospermum naphthoquinones and tissue compatible materials are hydrothermally synthesized at 60-90° C. in a molar ratio of 1:1 to form nano-microcrystalline particles.

5. A self-microemulsion of nano-crystals of lithospermum officinale extract, comprising: 10-150 parts of lithospermum extract nanocrystals, 10-25 parts of oil phase, 10-30 parts of surfactant, 2-15 parts of co-surfactant, 5-20 parts of solid absorbent; Preferably, the lithospermum extract nanocrystals include: 5-100 parts of lithospermum naphthoquinone active ingredient extract, 1-100 parts of ionic cellulose gum, 1-100 parts of chitosan, 5-100 parts of polylactic acid, and 5-100 parts of sodium alginate.

6. The self-microemulsion of lithospermum erythrorhizon extract nanocrystals according to claim 5, characterized in that: The oil phase is any one or a combination of grape seed oil, evening primrose oil, CapmulMCM, ethyl oleate, sunflower oil, Capryol 90, coconut oil, corn oil, and castor oil; And / or, the surfactant is any one or a combination of cetearyl alcohol and sorbitan olivate, Cremophor EL, Solutol HS, Tween-(20, 60, 80), decaglycerol monolaurate, caprylic / capric macrogol glyceride, polyoxyacetic stearic acid, and Labrasol; And / or, the co-surfactant is any one or a combination of ethanol, PEG-400, PEG-600, polyglycerol ricinoleate, cetyl polyethylene glycol / polypropylene glycol, polyethylene glycol-dipolyhydroxystearate, and Transcutol P; And / or, the solid adsorbent is any one or a combination of gum arabic, isopropyl citrate, anhydrous calcium carbonate, magnesium aluminum silicate, silicon dioxide, and mannitol.

7. A method for preparing self-microemulsion of nanocrystals of lithospermum officinale extract, comprising: (1) using hydrothermal complexation to form nano-crystal particles by combining lithospermum erythrorhizon extract with ionic cellulose gum, polylactic acid, sodium alginate and chitosan oligosaccharide; (2) adding the lithospermum erythrorhizon extract nano-crystal particles obtained in step (1) into the oil phase and stirring and dissolving them to form an oil phase system; (3) mixing and stirring the surfactant and the co-surfactant at a constant temperature of 60-80° C., and adding the mixture to the oil phase system obtained in step (2) to obtain a liquid self-microemulsion; (4) At room temperature, a solid adsorbent is added to the liquid microemulsion system obtained in step (3) to obtain a solid self-microemulsion.

8. A composition comprising the lithospermum extract nano-microcrystal particles according to any one of claims 1-2, or the lithospermum extract nano-microcrystal particles prepared by the method according to any one of claims 3-4, or the self-microemulsion of the lithospermum extract nano-microcrystals according to any one of claims 5-6, or the self-microemulsion of the lithospermum extract nano-microcrystals prepared by the method according to claim 7.

9. The composition according to claim 8, characterized in that It is a tablet, capsule, soft capsule, granule, disintegrant, dispersant, pill, micropellet, oral liquid, gel, thermosensitive hydrogel, ointment, spray, tincture, patch, film, medical gauze, medical tape bandage, medical implant, facial mask, tissue, care product, oral care product or sustained-release agent.

10. Use of the lithospermum extract nano-microcrystalline particles according to any one of claims 1-2, or the lithospermum extract nano-microcrystalline particles prepared by the method according to any one of claims 3-4, or the self-microemulsion of lithospermum extract nano-microcrystalline according to any one of claims 5-6, or the self-microemulsion of lithospermum extract nano-microcrystalline prepared by the method according to claim 7, or the composition according to any one of claims 8-9 in the preparation of drugs, wherein the drugs are used for antibacterial, anti-inflammatory, anti-cancer, treatment and prevention of skin infections; preferably, the drugs are used for the treatment of flat warts, psoriasis, topical treatment of burns and promotion of wound healing, treatment of infant dermatitis, eczema, vaginitis, and cervicitis, and can also be used to improve human skin conditions, repair damage, promote cell metabolism, anti-inflammatory, and whiten the skin.

Images