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A kind of targeted pharmaceutical composition and application thereof loaded with amphotericin b and doxorubicin

A technology of amphotericin and composition, which is applied in the field of targeted drug composition co-loaded with amphotericin B and doxorubicin, can solve the physical and psychological burden of patients with toxic side effects and economic expenses, prolong the treatment period, and reduce the dosage of drugs improvement, etc.

Active Publication Date: 2021-05-04
JIANGNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At the same time, for leishmaniasis patients with AIDS or low immunity, the dosage of drugs needs to be increased and the treatment cycle needs to be extended, which brings about heavy burdens on patients' body and mind due to the side effects and economic expenditure.

Method used

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  • A kind of targeted pharmaceutical composition and application thereof loaded with amphotericin b and doxorubicin
  • A kind of targeted pharmaceutical composition and application thereof loaded with amphotericin b and doxorubicin
  • A kind of targeted pharmaceutical composition and application thereof loaded with amphotericin b and doxorubicin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1 Preparation of mannose-modified β-cyclodextrin propionate

[0033] (1) Synthesis of seven (6-azido-6-deoxy-2,3-di-O-propionyl)-β-cyclodextrin: 1.5 g of seven (6-azido-6-de O)-β-cyclodextrin and 4.5g of 4-dimethylaminopyridine were dissolved in 36mL of pyridine, and 8.2mL of propionic anhydride was added, then the temperature of the system was raised to 60°C, and stirred for 48 hours under nitrogen protection; the reaction After the solution was cooled to normal temperature, 200 mL of water was added, extracted 3 times with 150 mL of ethyl acetate, then excess anhydrous sodium sulfate was added to remove water, after filtration, the solvent was distilled off under reduced pressure, and finally purified by silica gel column (petroleum ether: acetic acid ethyl ester = 4:1);

[0034] (2) Synthesis of mannose-modified β-cyclodextrin propionate (Man7-β-CD-C3, MCC): 208 mg of seven (6-azido-6-deoxy-2,3-di- (O-propionyl)-β-cyclodextrin and 200 mg of propargyl D-mann...

Embodiment 2

[0041] Embodiment 2 A kind of preparation of pharmaceutical composition

[0042] The mannose-modified β-cyclodextrin propionate, 2 mg of amphotericin B, and 2 mg of doxorubicin prepared in Example 1 of 10 mg were weighed and dissolved in dimethyl sulfoxide (MCC:AmB:DOX molar ratio 1:0.5:0.5), the mass concentration of the solution is 0.1mg / mL, after fully dissolving and mixing uniformly, drop into 1 times the volume of ultrapure water, mix evenly, move into a dialysis bag and dialyze with ultrapure water, filter , to obtain nano micelles; the volume ratio of the dialysis system is 1:100-1:500, and the number of times of changing the dialysate is 5-10 times; the particle size range of the nano micelles is 100-200nm .

Embodiment 3

[0043] Embodiment 3 A kind of preparation of pharmaceutical composition

[0044] The mannose-modified β-cyclodextrin propionate, 2 mg of amphotericin B, and 2 mg of doxorubicin prepared in Example 1 of 10 mg were weighed and dissolved in dimethyl sulfoxide (MCC:AmB:DOX molar ratio 1:0.5:0.5), the mass concentration of the solution is 1mg / mL, after fully dissolving and mixing uniformly, drop into 1 times the volume of ultrapure water, mix evenly, move it into a dialysis bag and dialyze with ultrapure water, filter it, That is, nano micelles are obtained; the volume ratio of the dialysis system is 1:100-1:500, and the number of dialysate changes is 5-10 times; the particle size range of the nano micelles is 100-200nm.

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Abstract

The invention discloses a targeted pharmaceutical composition loaded with amphotericin B and doxorubicin and application thereof, belonging to the field of medicine and pharmacy. The present invention proposes a novel pharmaceutical composition for the treatment of leishmaniasis. Two drugs, amphotericin B and doxorubicin with fluorescent tracer, are simultaneously loaded on a pH-responsive drug with good biological safety. A pharmaceutical composition is formed in a carrier material, wherein the carrier material is composed of a hydrophilic mannose residue that actively targets macrophages, a β-cyclodextrin, and a hydrophobic propionyl group. The biological safety (cytotoxicity, hemolytic toxicity) of the pharmaceutical composition of the present invention is better, stability, pH response drug release, targeting ability and therapeutic efficiency have all been verified in the cell model, realized amphotericin B at the same time The synergistic effect with doxorubicin greatly reduces the dosage of drugs, reduces side effects and economic burden of patients, and is expected to play a huge role in clinical application.

Description

technical field [0001] The invention belongs to the technical field of medicine and biology, and in particular relates to a targeting drug composition co-carrying amphotericin B and doxorubicin and an application thereof. Background technique [0002] Description According to the statistics of the World Health Organization, leishmaniasis causes the death of about 26,000 to 65,000 people in the world, and the new infection of about 700,000 to 1,000,000 people. The disease often occurs in economically underdeveloped areas and is closely related to problems such as malnutrition, poor sanitation, low immunity (patients are complicated by immune diseases such as AIDS) and lack of economic resources. [0003] Leishmaniasis is a parasitic disease caused by the genus Leishmania, mainly including cutaneous leishmaniasis, mucosal leishmaniasis and visceral leishmaniasis. Among them, visceral leishmaniasis is the most serious, also known as kala-azar, mainly caused by Leishmania donov...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/107A61K47/40A61K47/26A61K31/7048A61K31/704A61P33/02
CPCA61K9/1075A61K31/704A61K31/7048A61K47/26A61K47/40A61P33/02A61K2300/00Y02A50/30
Inventor 胡静尹健魏朋
Owner JIANGNAN UNIV
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