CN-120960447-B - Intestinal targeted controlled release microalgae pharmaceutical composition, preparation method and application

Abstract

The invention discloses an intestinal targeted controlled release microalgae pharmaceutical composition, which comprises a hydrophobic drug, micelle materials and microalgae, wherein the hydrophobic drug is firstly loaded on the micelle materials to form drug-loaded micelles, so that the solubility of the hydrophobic drug is improved, and a drug-loaded micelle solution is permeated into microalgae cells instead of being attached to the surfaces of the microalgae through a passive water absorption process of the dry microalgae. The natural cell wall which is firm and acid-resistant of the microalgae is used as a first physical barrier to prevent the release of the hydrophobic medicament in the gastric acid environment, and the effective concentration and the retention time of the hydrophobic medicament at the action part of the intestinal tract are obviously improved, so that the therapeutic effect is better exerted, and the microalgae can be used for preparing medicaments for treating intestinal diseases and kidney diseases.

Inventors

• LIU XIANGRUI
• QIAN JIEJIE
• BAI HAO
• ZHOU MIN
• ZHOU TIANHUA

Assignees

• 浙江大学长三角智慧绿洲创新中心

Dates

Publication Date

20260508

Application Date

20251021

Claims (5)

1. 1. The intestinal tract targeted controlled release microalgae pharmaceutical composition is characterized by comprising a hydrophobic drug, a micelle material and microalgae, wherein the hydrophobic drug is loaded on the micelle material to form a drug-loaded micelle, and the drug-loaded micelle is inside the microalgae; The micelle material is caprylic/capric polyethylene glycol glyceride, and the mass ratio of the hydrophobic drug to the micelle material is 1:40-60; the microalgae are one or more of spirulina and chlorella; the mass ratio of the hydrophobic drug to the microalgae is 1:50-1000.
2. 2. The intestinal tract targeted controlled release microalgae pharmaceutical composition of claim 1, wherein the microalgae is chlorella.
3. 3. The intestinal targeted controlled release microalgae pharmaceutical composition of claim 1, wherein the particle size of the drug-loaded micelle is 10-1200 nm.
4. 4. The intestinal targeted controlled release microalgae pharmaceutical composition according to claim 1, wherein gel material and metal inorganic salt are also added into the intestinal targeted controlled release microalgae pharmaceutical composition, the gel material is a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, and the inorganic salt is one of sodium chloride, potassium chloride and calcium chloride; The mass ratio of the hydrophobic drug to the gel material is 1:190, 1:237.5, 1:285 or 1:332.5; When the mass ratio of the hydrophobic drug to the gel material is 1:190, the mass ratio of the hydrophobic drug to the metal inorganic salt is 1:19-47.5; when the mass ratio of the hydrophobic drug to the gel material is 1:237.5, the mass ratio of the hydrophobic drug to the metal inorganic salt is 1:8.55-47.5; when the mass ratio of the hydrophobic drug to the gel material is 1:285, the mass ratio of the hydrophobic drug to the metal inorganic salt is 1:0.95-19.
5. 5. The use of the intestinal targeted controlled release microalgae pharmaceutical composition according to any of claims 1-4 in preparing a medicament for treating inflammatory bowel disease.

Description

Intestinal targeted controlled release microalgae pharmaceutical composition, preparation method and application Technical Field The invention relates to the technical field of pharmaceutical preparations, in particular to an intestinal targeted controlled release microalgae pharmaceutical composition, a preparation method and application. Background Budesonide, chemical name 16 alpha, 17 alpha- (22R, S) -propylmethylenedioxy-pregna-1, 4-diene-11 beta, 21-dihydroxyl-3, 20-dione, molecular formula C 25H34O6, molecular weight 430.5, and structural formula shown below. Budesonide is a glucocorticoid which is primarily used for anti-inflammatory and immunomodulation and its indications cover a number of systemic diseases, and is often administered orally when used in the treatment of inflammatory bowel disease and primary immunoglobulin a (IgA) kidney disease. Budesonide is a class of low solubility, high permeability drugs whose absorption is primarily limited by the solubility of the drug itself. The solubility of budesonide is affected by the pH of the dissolution medium, which solubility increases with decreasing pH. Thus, budesonide is more absorbed due to its high solubility in the stomach and less absorbed due to its low solubility in the intestinal tract after oral administration. However, in the treatment of inflammatory bowel disease and primary immunoglobulin A (IgA) nephropathy, both drugs act in places other than the stomach, the focus of the former being distributed in the ileum, colon, cecum segments of the intestine, while the latter acts mainly on the Petri lymph node at the terminal ileum. After the budesonide is directly taken orally, the medicine is mainly dissolved and absorbed in the stomach, so that systemic toxic and side effects are easy to generate, and the dissolution and absorption of the medicine are less in the target intestinal segment, so that the curative effect is difficult to effectively exert. In order to solve the problem, research and development personnel have invented an enteric strategy of budesonide, for example, the Chinese patent document with publication number CN118591376A adopts an enteric polymer material to avoid the release of the drug in gastric juice and release after 2 hours in intestinal juice, the Chinese patent document with publication number CN115554246A adopts an amorphous mode to increase the solubility of budesonide, adopts hydroxypropyl methylcellulose acetate succinate to realize the enteric, and the Chinese patent document with publication number CN117157079A adopts hydroxypropyl methylcellulose as a pellet material. The above-mentioned patents can achieve effective enteric effect, but all adopt chemically synthesized high molecular polymers as materials for realizing intestinal release, and the process is complex for realizing colon release. Microalgae as a natural biological material has remarkable advantages in the development of novel drug delivery systems due to the characteristics of excellent biocompatibility, degradability and the like. However, the electronegativity of microalgae cell wall surfaces is often utilized in published reports, so that both drugs and gel materials adhere to their surfaces, and various natural channels and internal structures in the cell walls are not fully utilized for drug delivery. For example, patent (CN 119925260 a) discloses a method for preparing colon-targeted chlorella vulgaris/paeoniflorin hydrogel, in which both the drug and the hydrogel are outside the chlorella vulgaris, and only the chlorella vulgaris is used as a nutrient component containing polysaccharide and protein to regulate gastrointestinal functions, so that the drug delivery advantage of the chlorella vulgaris is not fully exerted. Patent (CN 119236091A) discloses a composition for treating meibomian gland dysfunction based on chlorella, which takes chlorella as a carrier to load dexamethasone, but the drug is adsorbed on the surface of the chlorella, the drug loading efficiency is obviously limited by the surface charge characteristics of the chlorella strain and external environment parameters (such as pH value and ionic strength), and the carrier advantages of the chlorella are not fully reflected. Therefore, there is a need to find a microalgae pharmaceutical composition which fully exerts the advantages of the natural structure and the carrier of microalgae and realizes the targeted delivery and intestinal slow release functions. Disclosure of Invention In order to solve the technical problems, the invention provides an intestinal targeted controlled release microalgae pharmaceutical composition, which comprises a hydrophobic drug, micelle materials and microalgae, wherein the hydrophobic drug is loaded on the micelle materials to form drug-loaded micelles, and the drug-loaded micelles are inside the microalgae; the lipid water distribution coefficient (log P) of the hydrophobic drug is 2-4. The microalgae pharmaceutical composition in