Efficient nano-drug delivery system and preparation process thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and relates to an efficient nano-drug delivery system and a preparation process thereof. The nano-drug delivery system disclosed by the invention is prepared from scutellarin, ginsenoside Rg1, phospholipid, 4-methyl-free sterol, L-methionine and glucosamine. The stability and the drug loading capacity of the nano-drug delivery system are improved by preferably selecting auxiliary materials, the stability of the encapsulated traditional Chinese medicine effective components scutellarin and ginsenoside Rg1 is high, and the nano-drug delivery system has important theoretical significance and application value for promoting modernization of traditional Chinese medicine.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical preparations, and in particular relates to an efficient nano drug delivery system and a preparation process thereof. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] With the continuous development of modern medicine, the demand for efficient drug delivery systems is becoming increasingly urgent. Take paclitaxel as an example. It is a natural cancer drug widely used to treat cancers such as ovarian, breast and lung cancer. However, due to its low bioavailability and poor water solubility, it is very inconvenient to use and is accompanied by significant and unpredictable side effects. Liposome nano drug delivery system has become one of the hot spots in the current drug research and development field due to its unique advantages. As an effective drug delivery carrier, liposomes have been widely used in drug delivery systems due to their good biocompatibility, controlled release and low toxicity. Liposomes are composed of natural or synthetic lipid molecules, which can encapsulate water-soluble or fat-soluble drugs, avoid premature degradation or elimination of drugs in the body, improve the bioavailability of drugs, and achieve efficient delivery of drugs at targeted sites.

[0004] Chinese patent publication number CN102138898A discloses a novel long-circulating nanoliposome and a preparation method thereof, wherein a high phase transition temperature lipid and cholesterol are used as membrane materials to prepare a long-circulating nanoliposome.

[0005] A Chinese patent with publication number CN 101493444 A discloses a method for detecting scutellarin proliposomes, wherein the scutellarin proliposomes contain scutellarin 5 to 10 parts, soybean lecithin 10 to 40 parts, vitamin E 0.5 to 2 parts, and mannitol or lactose 20 to 80 parts.

[0006] The Chinese patent with publication number CN 116983406 A discloses that ginsenoside liposomes are used as adjuvants for tumor antigens. Ginsenoside liposomes can be used as immune adjuvants for tumor vaccines, which can significantly improve and enhance the effect of tumor antigen vaccines and are suitable as an auxiliary treatment for advanced tumors, especially as an adjuvant for tumor antigen vaccines to provide better immune response.

[0007] However, existing liposome drug delivery systems still face some challenges, including low drug loading efficiency and poor stability of active ingredients. Summary of the invention

[0008] The present invention integrates modern nanomedicine, liposome drug delivery and traditional Chinese medicine to construct a new type of Chinese medicine nanoliposome drug delivery system, provides an efficient nano drug delivery system and its preparation process, improves the stability and bioavailability of active ingredients of Chinese medicine, and realizes efficient treatment of major diseases with active ingredients of Chinese medicine.

[0009] The nano drug delivery system of the present invention comprises, by weight ratio, 0.1 to 1 parts of scutellaria baicalin, 0.2 to 2 parts of ginsenoside Rg1, 5 to 10 parts of phospholipids, 1 to 5 parts of 4-methyl-free sterols, 0.1 to 0.5 parts of L-methionine, and 0.1 to 0.3 parts of glucosamine.

[0010] The preparation method of the nano drug delivery system comprises the following steps:

[0011] (1) dissolving scutellariae baicalin, phospholipids and 4-methyl-free sterol in an organic solvent, and performing vacuum rotary evaporation in a water bath at 35°C±5°C until a thin film is formed (depending on the distillation of the distillate, the temperature is gradually increased from 30°C to 40°C);

[0012] (2) Ginsenoside Rg1, glucosamine and L-methionine were dissolved in a buffer solution of pH 5.5 to 7.5, added to the film for hydration, and vacuum evaporated in a water bath at 35°C ± 5°C, and homogenized under high pressure to obtain a nano drug delivery system.

[0013] Furthermore, the phospholipid is soybean lecithin and / or egg yolk lecithin; the 4-methyl-free sterol is β-sitosterol and / or stigmasterol; the particle size of the nano drug delivery system is ≤500nm; the buffer solution is selected from at least one of phosphate buffer solution, acetate buffer solution, and ethylenediaminetetraacetate buffer solution; the pressure range of the high-pressure homogenization is set at 20 to 80MPa, and the number of cycles of homogenization is 2 to 6 times; the organic solvent is selected from at least one of chloroform, methanol, and ethanol.

[0014] Baicalin is one of the main active ingredients extracted from the plant Scutellaria baicalensis, and has multiple biological activities such as anti-inflammatory, antioxidant, and antibacterial. Studies have shown that baicalin also has a significant effect in anti-tumor. The present invention encapsulates baicalin and ginsenoside Rg1 in a liposome system, which means that the nano drug delivery system of the present invention is provided for the preparation of anti-tumor drugs.

[0015] Compared with the prior art, the technical effects of the present invention are:

[0016] The nano drug delivery system containing baicalin and ginsenoside Rg1 of the present invention has good stability under the optimization effect of excipients. Under high temperature and high humidity experimental conditions, the nano drug delivery system of the present invention has stable particle size and high drug loading capacity, and the encapsulated effective ingredients of traditional Chinese medicine baicalin and ginsenoside Rg1 have high stability, which helps to enrich the scientific research connotation of traditional Chinese medicine and expand the application scope of nano drug delivery systems. It has important theoretical significance and application value for promoting the modernization of traditional Chinese medicine. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 : The content of baicalin in the nano drug delivery systems of Examples 1 to 3 and Comparative Examples 1 to 5.

[0018] Figure 2 : The content of ginsenoside Rg1 in the nanodrug delivery systems of Examples 1 to 3 and the nanodrug delivery systems of Comparative Examples 1 to 5. DETAILED DESCRIPTION

[0019] In order to make the purpose and technical solution of the present invention clearer, the present invention is further described below in conjunction with embodiments, but the protection scope of the present invention is not limited to these embodiments, and the embodiments are only used to explain the present invention. It should be understood by those skilled in the art that any changes or equivalent substitutions that do not deviate from the concept of the present invention are included in the protection scope of the present invention.

[0020] Example 1 Nano drug delivery system

[0021] formula:

[0022]

[0023] Preparation method:

[0024] (1) Dissolve scutellariae glycoside, phospholipids and 4-methyl-free sterol in 100 ml of chloroform and evaporate under reduced pressure in a water bath at 35°C ± 5°C until a thin film is formed;

[0025] (2) Ginsenoside Rg1, glucosamine and L-methionine were dissolved in 50 ml of acetate buffer solution at pH 6.5, added to the film for hydration, and vacuum evaporated in a water bath at 35°C for 10 min. The film was homogenized under high pressure with the pressure range set at 50 MPa and the number of cycles was 4 to obtain a nano drug delivery system.

[0026] Example 2 Nano drug delivery system

[0027] formula:

[0028]

[0029] Preparation method:

[0030] (1) Dissolve scutellarin, phospholipids, and 4-methyl-free sterol in 80 ml of chloroform and ethanol in a volume ratio of 4:1, and evaporate under reduced pressure in a water bath at 35°C ± 5°C until a thin film is formed;

[0031] (2) Ginsenoside Rg1, glucosamine and L-methionine were dissolved in 30 ml of ethylenediaminetetraacetic acid buffer solution at pH = 5.5, added to the film for hydration, and vacuum evaporated in a 35°C water bath for 10 min. The film was homogenized under high pressure with the pressure range set at 20 MPa and the number of cycles was 6 to obtain a nano drug delivery system.

[0032] Example 3 Nano drug delivery system

[0033] formula:

[0034]

[0035] Preparation method:

[0036] (1) Dissolve baicalin, phospholipids, and 4-methyl-free sterol in 150 ml of chloroform and methanol in a volume ratio of 2:1, and evaporate under reduced pressure in a water bath at 35°C ± 5°C until a thin film is formed;

[0037] (2) Ginsenoside Rg1, glucosamine and L-methionine were dissolved in 100 ml of phosphate buffer solution at pH = 7.5, added to the film for hydration, and vacuum evaporated in a water bath at 35°C for 10 min. The film was homogenized under high pressure with the pressure range set at 80 MPa and the number of cycles of homogenization was 2 to obtain a nano drug delivery system.

[0038] Comparative Example 1 Nano drug delivery system

[0039] formula:

[0040]

[0041] Preparation method:

[0042] (1) Dissolve scutellariae glycoside, phospholipids and 4-methyl-free sterol in 100 ml of chloroform and evaporate under reduced pressure in a water bath at 35°C ± 5°C until a thin film is formed;

[0043] (2) Ginsenoside Rg1 and glucosamine were dissolved in 50 ml of acetate buffer solution at pH 6.5, added to the film for hydration, and vacuum evaporated in a water bath at 35°C for 10 min. The film was homogenized under high pressure with the pressure range set at 50 MPa and the number of cycles was 4 to obtain a nano drug delivery system.

[0044] Comparative Example 2 Nano drug delivery system

[0045] formula:

[0046]

[0047] Preparation method:

[0048] (1) Dissolve scutellariae glycoside, phospholipids and 4-methyl-free sterol in 100 ml of chloroform and evaporate under reduced pressure in a water bath at 35°C ± 5°C until a thin film is formed;

[0049] (2) Ginsenoside Rg1 and L-methionine were dissolved in 50 ml of acetate buffer solution at pH 6.5, added to the film for hydration, and vacuum evaporated in a water bath at 35°C for 10 min. The film was homogenized under high pressure with the pressure range set at 50 MPa and the number of cycles was 4 to obtain a nano drug delivery system.

[0050] Comparative Example 3 Nano drug delivery system

[0051] formula:

[0052]

[0053] Preparation method:

[0054] (1) Dissolve baicalin, phospholipids, and cholesterol in 100 ml of chloroform and evaporate under reduced pressure in a water bath at 35°C ± 5°C until a thin film is formed;

[0055] (2) Ginsenoside Rg1, glucosamine and L-methionine were dissolved in 50 ml of acetate buffer solution at pH 6.5, added to the film for hydration, and vacuum evaporated in a water bath at 35°C for 10 min. The film was homogenized under high pressure with the pressure range set at 50 MPa and the number of cycles was 4 to obtain a nano drug delivery system.

[0056] Comparative Example 4 Nano drug delivery system

[0057] formula:

[0058]

[0059] Preparation method:

[0060] (1) Dissolve scutellariae glycoside, phospholipids and 4-methyl-free sterol in 100 ml of chloroform and evaporate under reduced pressure in a water bath at 35°C ± 5°C until a thin film is formed;

[0061] (2) Ginsenoside Rg1, L-cysteine ​​and glucosamine were dissolved in 50 ml of acetate buffer solution at pH 6.5, added to the film for hydration, and vacuum evaporated in a water bath at 35°C for 10 min. The film was homogenized under high pressure with the pressure range set at 50 MPa and the number of cycles was 4 to obtain a nano drug delivery system.

[0062] Comparative Example 5 Nano drug delivery system

[0063] formula:

[0064]

[0065] Preparation method:

[0066] (1) Dissolve scutellariae glycoside, phospholipids and 4-methyl-free sterol in 100 ml of chloroform and evaporate under reduced pressure in a water bath at 35°C ± 5°C until a thin film is formed;

[0067] (2) Ginsenoside Rg1, glucosamine and L-methionine were dissolved in 50 ml of acetate buffer solution at pH 6.5, added to the film for hydration, and vacuum evaporated in a water bath at 35°C for 10 min. The film was homogenized under high pressure with the pressure range set at 50 MPa and the number of cycles was 4 to obtain a nano drug delivery system.

[0068] Particle size of nano drug delivery systems

[0069] The particle size of liposomes is an important indicator for evaluating their quality and biological behavior (such as drug release, absorption, etc.). The particle sizes of the nano drug delivery systems of Examples 1 to 3 and Comparative Examples 1 to 5 were measured by dynamic light scattering to evaluate their uniformity and average particle size. Experimental conditions: 40°C ± 2°C, relative humidity 75% ± 5%.

[0070] Table 1 Particle size of nano drug delivery system

[0071]

[0072]

[0073] As shown in Table 1, the particle size of the nano drug delivery system of the present invention is ≤500 nm before and after the experiment, and has high stability and high particle size uniformity.

[0074] Drug loading capacity of nano drug delivery system

[0075] Drug loading refers to the ratio of the mass of the drug contained in the nanodrug delivery system to the total mass of the liposomes, usually expressed as a percentage. It is an important parameter for evaluating the drug loading capacity of the nanodrug delivery system.

[0076] Table 2 Drug loading of nano drug delivery system

[0077]

[0078]

[0079] As shown in Table 2, the nano drug delivery system of the present invention has a high drug loading capacity, which means that more drug components can be delivered in a carrier per unit volume or unit mass, ensuring that patients can still obtain sufficient drug efficacy at a lower dosage, thereby improving the therapeutic effect and increasing the bioavailability of the drug in the body by improving the drug delivery efficiency.

[0080] Stability of baicalin and ginsenoside Rg1, active ingredients of traditional Chinese medicine

[0081] The contents of baicalin and ginsenoside Rg1 in the nanodrug delivery system before and after the experiment were detected by high performance liquid chromatography according to the 2020 edition of the Chinese Pharmacopoeia.

[0082] Figure 1 It is the content of scutellariae in the nano drug delivery systems of Examples 1 to 3 and the nano drug delivery systems of Comparative Examples 1 to 5. Figure 2 The content of ginsenoside Rg1 in the nano drug delivery systems of Examples 1 to 3 and Comparative Examples 1 to 5. The data show that the nano drug delivery system of the present invention is more stable in carrying the effective ingredients of traditional Chinese medicine, baicalin and ginsenoside Rg1. Under high temperature and high humidity conditions, the content of the effective ingredients is less reduced, which is conducive to the efficient delivery of drugs.

Claims

1. A nano drug delivery system, characterized in that: The nano drug delivery system comprises, by weight ratio, 0.1 to 1 parts of scutellaria baicalin, 0.2 to 2 parts of ginsenoside Rg1, 5 to 10 parts of phospholipids, 1 to 5 parts of 4-methyl-free sterol, 0.1 to 0.5 parts of L-methionine, and 0.1 to 0.3 parts of glucosamine.

2. The nano drug delivery system according to claim 1, characterized in that The phospholipids are soybean lecithin and / or egg yolk lecithin.

3. The nano drug delivery system according to claim 1, characterized in that The 4-methyl-free sterol is β-sitosterol and / or stigmasterol.

4. The nano drug delivery system according to claim 1, characterized in that The particle size of the nano drug delivery system is ≤500nm.

5. The nano drug delivery system according to claim 1, characterized in that The phospholipid is soybean lecithin, and the 4-methyl-free sterol is β-sitosterol.

6. A method for preparing the nano drug delivery system according to claim 1, characterized in that: The preparation method comprises the following steps: (1) dissolving scutellariae scutellariae, phospholipids and 4-methyl-free sterol in an organic solvent, and performing vacuum rotary evaporation in a water bath at 35°C±5°C until a thin film is formed; (2) Ginsenoside Rg1, glucosamine and L-methionine were dissolved in a buffer solution of pH 5.5 to 7.5, added to the film for hydration, and vacuum evaporated in a water bath at 35°C ± 5°C, and homogenized under high pressure to obtain a nano drug delivery system.

7. The preparation method according to claim 6, characterized in that: The buffer solution is selected from at least one of a phosphate buffer solution, an acetate buffer solution, and an ethylenediaminetetraacetate buffer solution.

8. The preparation method according to claim 6, characterized in that: The pressure range of the high-pressure homogenization is set at 20-80 MPa, and the number of cycles of homogenization is 2-6 times.

9. The preparation method according to claim 6, characterized in that: The organic solvent is selected from at least one of chloroform, methanol and ethanol.

10. Use of the nano drug delivery system according to claim 1 in the preparation of anti-tumor drugs.

Images