An efficient nano drug delivery system and its preparation process

Abstract

The present invention belongs to the field of pharmaceutical preparation technology and relates to an efficient nano drug delivery system and its preparation process. The nano drug delivery system of the present invention comprises scutellarin, ginsenoside Rg1, phospholipids, 4-methyl-free sterol, L-methionine, and glucosamine. By optimizing excipients, the present invention improves the stability and drug loading capacity of the nano drug delivery system. The entrapped effective ingredients of traditional Chinese medicine, scutellarin and ginsenoside Rg1, are highly stable, and have important theoretical significance and application value for promoting the 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 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 those 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 naturally derived 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. Due to its unique advantages, liposome nanodrug delivery systems have become one of the hot topics in the current drug research and development field. 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 and can encapsulate water-soluble or fat-soluble drugs, preventing premature degradation or elimination of drugs in the body, improving drug bioavailability, and achieving efficient drug delivery to targeted sites.

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

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

[0006] Chinese patent publication number CN 116983406 A discloses the use of ginsenoside liposomes as an adjuvant for tumor antigens. Using ginsenoside liposomes as an immune adjuvant for tumor vaccines can significantly improve and enhance the effectiveness of tumor antigen vaccines. It is suitable for use as an adjuvant for advanced tumors, particularly as an adjuvant for tumor antigen vaccines, providing a stronger 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 Chinese medicine nanoliposome drug delivery system, provides an efficient nanodrug delivery system and its preparation process, improves the stability and bioavailability of Chinese medicine active ingredients, and realizes the efficient treatment of major diseases with Chinese medicine active ingredients.

[0009] The nano drug delivery system of the present invention comprises, by mass ratio, 0.1 to 1 parts of scutellarin, 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) Dissolve scutellarin, phospholipids, and 4-methyl-free sterol in an organic solvent and evaporate under reduced pressure 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 Scutellaria baicalensis plant and possesses multiple biological activities, including anti-inflammatory, antioxidant, and antibacterial properties. Studies have shown that baicalin also has significant anti-tumor effects. The present invention encapsulates baicalin and ginsenoside Rg1 in a liposome system, providing the use of the nano-drug delivery system described herein in 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 scutellarin and ginsenoside Rg1 of the present invention has good stability under the optimal 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 traditional Chinese medicine active ingredients scutellarin and ginsenoside Rg1 have high stability, which helps to enrich the scientific research connotation of traditional Chinese medicine and expand the application scope of the nano drug delivery system. 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 scutellarin 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 nano drug delivery systems of Examples 1 to 3 and the nano drug delivery systems of Comparative Examples 1 to 5. DETAILED DESCRIPTION

[0019] In order to make the purpose and technical solution of the present invention more clear, the present invention is further described below in conjunction with the embodiments, but the scope of protection of the present invention is not limited to these embodiments, and the embodiments are only used to illustrate 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 scope of protection of the present invention.

[0020] Example 1 Nano drug delivery system

[0021] formula:

[0022]

[0023] Preparation method:

[0024] (1) Dissolve scutellarin, 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 forms.

[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 evaporated in a water bath at 35°C for 10 min under reduced pressure. The film was homogenized under high pressure with the pressure range set at 50 MPa and the number of homogenization 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 (volume ratio: 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 homogenization 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 scutellarin, phospholipids, and 4-methyl-free sterol in 150 ml of chloroform and methanol (volume ratio: 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 35°C water bath for 10 min. The film was homogenized under high pressure with the pressure range set at 80 MPa and the number of homogenization cycles was 2 to obtain a nano drug delivery system.

[0038] Comparative Example 1 Nanodrug delivery system

[0039] formula:

[0040]

[0041] Preparation method:

[0042] (1) Dissolve scutellarin, 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 forms.

[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 evaporated in a water bath at 35°C for 10 min under reduced pressure. The film was homogenized under high pressure with the pressure range set at 50 MPa and the number of homogenization cycles was 4 to obtain a nano drug delivery system.

[0044] Comparative Example 2 Nanodrug Delivery System

[0045] formula:

[0046]

[0047] Preparation method:

[0048] (1) Dissolve scutellarin, 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 forms.

[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 then rotary 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 homogenization cycles was 4 to obtain a nano drug delivery system.

[0050] Comparative Example 3 Nanodrug delivery system

[0051] formula:

[0052]

[0053] Preparation method:

[0054] (1) Dissolve scutellarin, 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 forms.

[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 evaporated in a water bath at 35°C for 10 min under reduced pressure. The film was homogenized under high pressure with the pressure range set at 50 MPa and the number of homogenization cycles was 4 to obtain a nano drug delivery system.

[0056] Comparative Example 4 Nanodrug Delivery System

[0057] formula:

[0058]

[0059] Preparation method:

[0060] (1) Dissolve scutellarin, 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 forms.

[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 homogenization cycles was 4 to obtain a nano drug delivery system.

[0062] Comparative Example 5 Nanodrug Delivery System

[0063] formula:

[0064]

[0065] Preparation method:

[0066] (1) Dissolve scutellarin, 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 forms.

[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 evaporated in a water bath at 35°C for 10 min under reduced pressure. The film was homogenized under high pressure with the pressure range set at 50 MPa and the number of homogenization 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 and absorption). The particle size of the nanodrug delivery systems of Examples 1 to 3 and Comparative Examples 1 to 5 was 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 was ≤500 nm before and after the experiment, and the system had high stability and high particle size uniformity.

[0074] Drug loading capacity of nano drug delivery systems

[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 capacity 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 ingredients 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 treatment 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 The content of scutellarin 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 data show that the nanodrug delivery systems of Examples 1 to 3 and Comparative Examples 1 to 5 show the content of ginsenoside Rg1. The data show that the nanodrug delivery systems of the present invention are more stable in carrying the traditional Chinese medicine active ingredients scutellarin and ginsenoside Rg1. Under high temperature and high humidity conditions, the active ingredient content is less reduced, which facilitates efficient drug delivery.

Claims

1. A liposome nano drug delivery system, characterized in that: The liposome nano drug delivery system comprises, by mass ratio, 0.1 to 1 parts of scutellarin, 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; the phospholipids are soybean lecithin and / or egg yolk lecithin; and the 4-methyl-free sterols are β-sitosterol and / or stigmasterol.

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

3. The liposome 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.

4. A method for preparing the liposome nano drug delivery system according to claim 1, characterized in that: The preparation method comprises the following steps: (1) Dissolve scutellarin, phospholipids, and 4-methyl-free sterol in an organic solvent and evaporate under reduced pressure 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 5.5-7.5, 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 liposome nano-drug delivery system.

5. The preparation method according to claim 4, 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.

6. The preparation method according to claim 4, 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.

7. The preparation method according to claim 4, characterized in that The organic solvent is selected from at least one of chloroform, methanol and ethanol.

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

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