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Pharmaceutical liposome containing Adriamycin and immunoadjuvant combination and preparation method for pharmaceutical liposome

An immunoadjuvant and doxorubicin technology, used in liposome delivery, drug combination, pharmaceutical formulations, etc., can solve the problems of drug resistance, difficult to inhibit tumor cell growth, insufficient anti-tumor efficacy, etc., and achieve improved stability. Effect

Pending Publication Date: 2020-12-29
上海舜纳生物科技有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although liposome technology effectively reduces the toxic and side effects of doxorubicin, Doxil® still produces drug resistance and insufficient anti-tumor efficacy in tumor chemotherapy, making it difficult to inhibit tumor cell growth with a single drug or preparation

Method used

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  • Pharmaceutical liposome containing Adriamycin and immunoadjuvant combination and preparation method for pharmaceutical liposome
  • Pharmaceutical liposome containing Adriamycin and immunoadjuvant combination and preparation method for pharmaceutical liposome
  • Pharmaceutical liposome containing Adriamycin and immunoadjuvant combination and preparation method for pharmaceutical liposome

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Example 1: Preparation of doxorubicin and CpG&lipopolysaccharide co-loaded liposomes (ADR / CpG&LPS-Lip)

[0052] Preparation prescription (50ml volume):

[0053] Adriamycin Hydrochloride 100mg

[0054] CpG 10mg

[0055] Lipopolysaccharide 10mg

[0056] Distearic Lecithin (DSPC) 640mg

[0057] Distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000) 220mg

[0058] DOTAP 140mg

[0059] Cholesterol 190mg

[0060] Vitamin E 2.4mg

[0061] Citric acid 1120mg

[0062] Anhydrous sodium carbonate 1600mg

[0063] Sucrose about 4500mg

[0064] Glycine about 50mg

[0065] Dilute to the required volume with water for injection

[0066] The preparation process is as follows:

[0067] According to the formula, DSPC, DSPE-PEG2000, DOTAP, cholesterol and vitamin E were mixed in 4% ethanol solution and heated to 50°C; another ammonium sulfate with a concentration of 250mM was prepared to dissolve doxorubicin hydrochloride, CpG and lipopolysaccharide and heat...

Embodiment 2

[0068] Example 2: Preparation of doxorubicin and PolyICLC co-loaded liposomes (ADR / PolyICLC-Lip)

[0069] Preparation prescription (50ml volume):

[0070] Adriamycin Hydrochloride 100mg

[0071] PolyICLC 20mg

[0072] Hydrogenated Soy Lecithin (HSPC) 760mg

[0073] Distearoylphosphatidylethanolamine-polyethylene glycol 3400 (DSPE-PEG3400) 220mg

[0074] Dlin-MC3-DMA 220mg

[0075] Cholesterol 220mg

[0076] Vitamin E 2.0mg

[0077] Succinic acid 600mg

[0078] Sodium hydroxide 340mg

[0079] Lactose about 2250mg

[0080] Glycine about 70mg

[0081] Dilute to the required volume with water for injection

[0082] The preparation process is as follows:

[0083] Select HSPC, DSPE-PEG3400, Dlin-MC3-DMA, cholesterol and vitamin E in 4% ethanol solution according to the formula and mix them uniformly and heat up to 65°C; prepare ammonium sulfate with a concentration of 250mM to dissolve doxorubicin hydrochloride and PolyICLC and heat up to 55°C -65 DEG C, and under the co...

Embodiment 3

[0084] Example 3: Preparation of doxorubicin and MPL-TDM co-loaded liposomes (ADR / MPL-TDM-Lip)

[0085] Preparation prescription (50ml volume):

[0086] Adriamycin Hydrochloride 100mg

[0087] MPL-TDM 35mg

[0088] Distearate Phosphatidylglycerol (DSPG) 160mg

[0089] Distearoylphosphatidylethanolamine-polyethylene glycol 5000 (DSPE-PEG5000) 220mg

[0090] Egg Yolk Phosphatidylglycerol (EPG) 240mg

[0091] c12-200 220mg

[0092] Cholesterol 220mg

[0093] Vitamin E 1.6mg

[0094] Citric acid 1240mg

[0095] Sodium hydroxide 520mg

[0096] Sucrose about 2250mg

[0097] Glycine about 50mg

[0098] Dilute to the required volume with water for injection

[0099] The preparation process is as follows:

[0100] Select DSPG, EPG, c12-200, DSPE-PEG5000, cholesterol and vitamin E in 4% ethanol solution and mix evenly to raise the temperature to 60°C according to the formula; prepare ammonium sulfate with a concentration of 250mM to dissolve doxorubicin hydrochloride and MPL...

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Abstract

The invention provides a pharmaceutical liposome containing a chemical Adriamycin and immunoadjuvant combination. The nano liposome efficiently loads Adriamycin and an immunization antigen and can stably and long circulate in vivo, the immunization antigen is delivered to a tumor microenvironment while toxic or side effects of the Adriamycin are lowered, and the liposome can exert a chemotherapy-immunization combined therapeutic action on tumors so as to achieve the aim of inhibiting tumorous growth and transferring.

Description

technical field [0001] The present invention relates to a drug liposome preparation for combination therapy of tumor chemotherapy and immunity, specifically a nano liposome co-loaded with adriamycin and immune adjuvant and its preparation. Background technique [0002] Clinical treatments for cancer include surgery, chemotherapy (chemotherapy), radiation therapy (RT), targeted therapy, and immunotherapy. In general, chemotherapy is an indispensable means of tumor treatment. [0003] Chemotherapy usually uses systemic administration, not only killing tumor cells; it also has clear toxic side effects on normal human cells, such as nausea, hair loss, hematopoietic toxicity, reduction of hematopoietic progenitor cell mobilization from bone marrow to peripheral blood, anemia, bone marrow Inhibition, pancytopenia, thrombocytopenia, neutropenia, lymphopenia, leukopenia. These side effects often limit the dose and frequency of chemotherapy drugs administered. [0004] Adriamycin ...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/24A61K47/28A61K31/704A61K39/39A61P35/00
CPCA61K9/127A61K31/704A61K39/39A61K47/24A61K47/28A61K2039/55561A61K2039/55572A61P35/00A61K2300/00
Inventor 陈怀文高洁尹川张莹莹杨冬梅谢方圆刘俊杰于永生贺智明姜普
Owner 上海舜纳生物科技有限公司
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