Hydrogel containing doxorubicin and immunologic adjuvant combined drug liposome for injection and preparation method thereof

A technology of immune adjuvant and water for injection, which is applied in the field of hydrogel for injection containing liposome combined with doxorubicin and immune adjuvant and its preparation field, can solve the problem of insufficient anti-tumor effect, difficulty in inhibiting tumor cell growth, and resistance to tumor cells. medicine and other issues

Pending Publication Date: 2021-12-24
SHANGHAI UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, problems such as drug resistance and insufficient anti-tumor efficacy still occur during t

Method used

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  • Hydrogel containing doxorubicin and immunologic adjuvant combined drug liposome for injection and preparation method thereof
  • Hydrogel containing doxorubicin and immunologic adjuvant combined drug liposome for injection and preparation method thereof
  • Hydrogel containing doxorubicin and immunologic adjuvant combined drug liposome for injection and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Embodiment 1: prepare the PLGA-PEG-PLGA (polyglycolide-lactide-polyethylene glycol-polyglycolide lactide) hydrogel containing doxorubicin and CpG co-loaded liposomes, referred to as ( ADR / CpG-Lip) PLGA-Gel

[0048] Preparation prescription (50g quantitative):

[0049] Doxorubicin 100mg

[0050] CpG 10mg

[0051] Distearic Lecithin (DSPC) 640mg

[0052] DOTAP 140mg

[0053] PLGA-PEG-PLGA block copolymer 6g (PLGA(75 / 25)1870-PEG1500-PLAG(75 / 25)1870 or PLGA(75 / 25)1704-PEG1500-PLAG(75 / 25)1704)

[0054] Cholesterol 190mg

[0055] Vitamin E 2.4mg

[0056] Sodium dihydrogen phosphate 160mg

[0057] Sucrose 1g

[0058] Quantitative water for injection to 50g

[0059] The preparation process is as follows:

[0060] According to the formula, DSPC, DOTAP, cholesterol and vitamin E were mixed in 4% ethanol solution and heated to 65°C to form a lipid solution; another ammonium sulfate with a concentration of 250mM was prepared to dissolve doxorubicin and CpG and heated to 6...

Embodiment 2

[0061] Example 2: Preparation of PCL-PEG-PCL (polycaprolactone-polyethylene glycol-polycaprolactone) hydrogel containing doxorubicin and PolyICLC co-loaded liposomes, referred to as (ADR / PolyICLC-Lip) PCL-Gel

[0062] Preparation prescription (50g quantitative):

[0063] Doxorubicin 100mg

[0064] PolyICLC 20mg

[0065] Hydrogenated Soy Lecithin (HSPC) 760mg

[0066] Dlin-MC3-DMA 220mg

[0067] Cholesterol 220mg

[0068] PCL-PEG-PCL 6.4g (PCL2000-PEG1500-PCL2000 or PCL3400-PEG1500-PCL3400)

[0069] Vitamin E 2.0mg

[0070] Sucrose 2g

[0071] Sodium dihydrogen phosphate 240mg

[0072] Quantitative water for injection to 50g

[0073] The preparation process is as follows:

[0074] According to the recipe, HSPC, Dlin-MC3-DMA, cholesterol and vitamin E were mixed in 4% ethanol solution and heated to 55°C to form a lipid solution; another ammonium sulfate with a concentration of 250mM was prepared to dissolve doxorubicin and PolyICLC and heated to 60 ℃; and the lipid so...

Embodiment 3

[0075] Example 3: Preparation of PDLLA-PEG-PDLLA (poly D, L-lactide-polyethylene glycol-poly D, L-lactide) hydrogel containing doxorubicin and lipopolysaccharide co-loaded liposomes , referred to as (ADR / LPS-Lip) PDLLA-Gel

[0076] Preparation prescription (50g quantitative):

[0077] Doxorubicin 100mg

[0078] Lipopolysaccharide 35mg

[0079] Distearate Phosphatidylglycerol (DSPG) 160mg

[0080] Egg Yolk Phosphatidylglycerol (EPG) 240mg

[0081] c12-200 220mg

[0082] Cholesterol 220mg

[0083] Vitamin E 1.6mg

[0084] PDLLA(1500-2000)-PEG(1000-1500)-PDLLA(1500-2000) 8.5g

[0085] Sodium dihydrogen phosphate 200mg

[0086] Dilute to the required volume with water for injection

[0087] The preparation process is as follows:

[0088] According to the formula, DSPG, EPG, c12-200, cholesterol and vitamin E were mixed in 4% ethanol solution and heated to 58°C to form a lipid solution; another ammonium sulfate with a concentration of 250mM was prepared to dissolve doxoru...

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Abstract

The invention provides a hydrogel preparation containing doxorubicin and immunologic adjuvant combined drug liposome for injection, and the drug hydrogel is used for in-situ administration treatment of solid tumors. The doxorubicin and immunologic adjuvant co-loaded liposome can be slowly released from the hydrogel, the chemotherapy-immune combined treatment effect on tumors is developed, and the aim of inhibiting tumor growth and metastasis is achieved.

Description

technical field [0001] The invention relates to a hydrogel pharmaceutical preparation for tumor chemotherapy and immunotherapy, in particular to an injection hydrogel containing a combination of doxorubicin and immune adjuvant drug liposome and a preparation method thereof. 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 ...

Claims

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Application Information

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IPC IPC(8): A61K9/06A61K9/127A61K47/34A61K47/22A61K45/06A61K31/704A61K31/739A61P35/00A61P37/04
CPCA61K9/06A61K9/127A61K9/0019A61K47/34A61K47/22A61K45/06A61K31/704A61K31/739A61P35/00A61P37/04
Inventor 高洁陈怀文余作冲张莹莹解方圆冯茜毕建豪董银梅刘俊杰尹川
Owner SHANGHAI UNIV
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