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Composite lipid nanocapsule composition and preparation method and application thereof

A composite lipid and nanocapsule technology, which is applied in drug combination, capsule delivery, microcapsules, etc., can solve the problems of insufficient ability of targeted drug delivery, inapplicability of intravenous injection, and limitation of clinical application, etc., to improve drug stability Sex, improve solubility, improve the effect of treatment effect

Pending Publication Date: 2020-11-13
INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, since the particle size of the microcapsules prepared by this technology is about 4-5 μm, it is not suitable for intravenous administration, and the ability of targeted drug delivery is insufficient, which limits its clinical application.

Method used

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  • Composite lipid nanocapsule composition and preparation method and application thereof
  • Composite lipid nanocapsule composition and preparation method and application thereof
  • Composite lipid nanocapsule composition and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] The regulation surface negative charge effect of embodiment 1 ascorbyl palmitate

[0064] Lipid cores containing different proportions of ascorbyl palmitate were prepared and compared with normal liposomes without ascorbyl palmitate.

[0065] Table 1 Formulation and characterization of different ascorbyl palmitate ratios

[0066]

[0067] 1. The preparation method of prescription A1 (ordinary liposome):

[0068] (1) Dissolve the prescribed amount of phospholipids (PC:80-85%) and cholesterol in chloroform-methanol (88:12) to obtain a clear and transparent solution, and remove the organic solvent by rotary evaporation to obtain a lipid film.

[0069] (2) Place the lipid film obtained in step 1 in a water bath at 40-60° C., slowly add 25 mL of phosphate buffer (pH=7) containing about 0.2% Tween 80 under stirring to obtain a thick emulsion. The coarse emulsion is homogenized under high pressure to obtain liposomes.

[0070] 2. Preparation method of prescriptions A2-A5...

Embodiment 2

[0076] Comparison of different phospholipids of embodiment 2

[0077] The effect of using phospholipids containing different proportions of phosphatidylcholine (PC: 80%-100%) on the preparation of lipid core was investigated.

[0078] Table 2 Formulation and characterization of different phospholipids

[0079]

[0080] Preparation:

[0081] (1) Dissolve the prescribed amount of phospholipids and ascorbyl palmitate in methanol to obtain a clear and transparent solution, remove the methanol by vacuum rotary evaporation in a water bath at 30-40°C, and collect the resulting precipitate, that is, the mixed membrane material.

[0082] (2) Dissolving the mixed film material and medium-chain oil obtained in step 1 in dichloromethane to obtain a uniform solution, and removing the dichloromethane by vacuum rotary evaporation in a water bath at 30-40° C. to obtain a lipid-film complex.

[0083] (3) Put the lipid membrane complex obtained in step 2 in a water bath at 40-60° C., slowly ...

Embodiment 3

[0085] Comparison of different oils and fats of embodiment 3

[0086] The effect of using different oils on the preparation of nanocapsule lipid core was investigated.

[0087] Table 3 Recipe and characterization of different oil phases

[0088]

[0089] Preparation:

[0090] (1) Dissolve the prescribed amount of phospholipids (PC≥98%) and ascorbyl palmitate in methanol to obtain a clear and transparent solution, remove the methanol by vacuum rotary evaporation in a water bath at 30-40°C, and collect the resulting precipitate, which is the mixed membrane material.

[0091] (2) Dissolving the mixed film material obtained in step 1 and the oil phase of the prescription amount in dichloromethane to obtain a uniform solution, and removing the dichloromethane by vacuum rotary evaporation in a 30-40°C water bath to obtain a lipid-film complex.

[0092] (3) Place the lipid membrane complex obtained in step 2 in a 40-60°C water bath, slowly add 50 mL of phosphate buffer (pH=7) co...

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Abstract

The invention discloses a composite lipid nanocapsule composition and a preparation method and application thereof, and belongs to the technical field of medicines. The composite lipid nanocapsule composition is formed by combining a lipid core with negative charges on the surface, a first capsule wall layer with positive charges and a second capsule wall layer with negative charges through electrostatic adsorption between positive and negative charge groups, and can be used for intravenous injection, wherein the lipid core is a depot loaded with an anti-tumor drug, chitosan has the effects ofpromoting transmembrane transport, controlling drug release and the like, and low-molecular heparin coating the outer side of the nanocapsule can react with heparinase so that the nanocapsule is enriched and degraded at a malignant tumor part, and a tumor targeting function is realized. Besides, a carrier material used by the composition is high in biological safety, good in tumor targeting property, high in drug encapsulation efficiency, good in stability, controllable in release and simple in preparation method, and has a wide application prospect when being used for targeted delivery of antitumor drugs.

Description

technical field [0001] The invention belongs to the technical field of medicine and nanomedicine, and relates to a composite lipid nanocapsule composition, a preparation method and application thereof. Background technique [0002] Malignant tumor is one of the main diseases that threaten human health and cause death of patients. Chemotherapy is a conventional treatment for malignant tumors. However, chemotherapy drugs generally have defects such as non-selective treatment, high toxicity and side effects, and easy drug resistance of cancer cells, which are poorly tolerated by patients. In addition, many antitumor drugs also have physical and chemical properties defects such as poor water solubility and poor stability. Therefore, it is necessary to improve the physical and chemical properties of drugs through preparation technology, especially according to the biological characteristics of the tumor and its microenvironment, use preparation technology to improve the tumor ta...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/24A61K47/36A61K47/22A61K47/44A61K31/337A61P35/00
CPCA61K9/5161A61K9/5123A61K9/0019A61K31/337A61P35/00
Inventor 刘玉玲李琳王洪亮叶军夏学军汪仁芸
Owner INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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