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Combination medication containing liposome composition encapsulating drug and immune checkpoint inhibitor

A technology of immune checkpoint and liposome, which is applied in drug combination, liposome delivery, medical preparations containing active ingredients, etc., can solve the problems of insufficient improvement, and achieve less burden on the body, high half-life, strong Effect of antitumor activity

Active Publication Date: 2021-02-02
FUJIFILM CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, since the lipid composition constituting the liposome and the salt composition for precipitating topotecan have not been optimized, the improvement in AUC is not sufficient, and further improvement is required.

Method used

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  • Combination medication containing liposome composition encapsulating drug and immune checkpoint inhibitor
  • Combination medication containing liposome composition encapsulating drug and immune checkpoint inhibitor
  • Combination medication containing liposome composition encapsulating drug and immune checkpoint inhibitor

Examples

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preparation example Construction

[0145] (b) preparation of the aqueous phase;

[0146] (c) liposome particle formation based on emulsification;

[0147] (d) extruder-based sizing;

[0148] (e) dialysis-based replacement of the liposome extracellular aqueous phase;

[0149] (f) entrapping the drug in liposome particles based on remote loading; and

[0150] (g) Dialysis-based removal of drugs from the external aqueous phase.

[0151] (d) Extruder-based sizing may or may not be performed.

[0152]

[0153] In (a) preparation of the oil phase, the components constituting the liposome (diacylphosphatidylethanolamine modified with a hydrophilic polymer, dihydrosphingomyelin, and cholesterol) and an organic solvent are mixed, and the mixture is subjected to The above-mentioned components are dissolved by raising the temperature, so that an oil phase can be produced.

[0154] The organic solvent used in the oil phase is not particularly limited, but for example, a water-soluble organic solvent that can be mixe...

Embodiment

[0221] Hereinafter, although an Example is given and this invention is demonstrated concretely, this invention is not limited to these at all. It is understood that the present invention can be variously changed or modified by those skilled in the art. Such changes and modifications are included in the present invention as long as they do not depart from the scope of the present invention. Commercial items were used for various reagents used in Examples unless otherwise specified.

[0222] SM represents Sphingomyelin (COATSOME NM-10, manufactured by NOF CORPORATION).

[0223] Egg-derived DHSM means dihydrosphingomyelin obtained by hydrogenating egg-derived SM (a synthetic product obtained by hydrogenating COATSOME NM-10 (manufactured by NOF CORPORATION)). This egg-derived DHSM has 2 alkyl chains having 16 carbon atoms in 70 to 80% of the whole, and the remainder contains a mixture of DHSMs having different alkyl chain lengths.

[0224] The total synthetic DHSM means dihydro...

Embodiment 1～8

[0260] (a) Preparation of oil phase

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Abstract

The present invention addresses the problem of providing a medication obtained by combining a liposome composition in which a liposome encapsulates a drug with an immune checkpoint inhibitor. The present invention provides a medication involving concurrent or successive administration of: (A) a liposome composition containing, as constituent components of a liposome film, a cholesterol, dihydrosphingomyelin, diacylphosphatidyl ethanol amine modified with a hydrophilic polymer, wherein the liposome composition encapsulates a drug, the internal water phase thereof contains ammonium sulfate, themolar ratio of the sulfate ions of the internal water phase with respect to the entire water phase drug is 0.36 or more; and (B) an immune checkpoint inhibitor.

Description

technical field [0001] The present invention relates to a medicine that combines a liposome composition containing a drug and an immune checkpoint inhibitor and administers them simultaneously or sequentially. Background technique [0002] In recent years it has been known that cancer exploits systems to evade immune surveillance mechanisms. Cancer immunotherapy is a therapy that inhibits the progression of cancer or treats cancer by acting on the immune surveillance mechanism of cancer patients to enhance immunity against cancer. Immune checkpoint molecules such as CTLA-4, PD-1 or its ligand (ligand) ie PD-L1 are known as molecules used in such an evasion system (Patent Documents 1 and 2). [0003] Also, co-administration of human anti-PD-1 or an antigen-binding portion thereof and a chemotherapeutic agent is described in which two anticancer agents that act by different mechanisms are administered, and their effect on Human tumor cells cause cytotoxicity (Patent Document...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K31/404A61K31/4745A61K31/704A61K47/04A61K47/24A61K47/28A61P35/00
CPCA61K31/4745A61K31/404A61P35/00A61K31/704A61K47/28A61K45/06C07K16/2827A61K39/39558A61K2039/505A61K9/1271A61K9/1277A61K2300/00A61K39/3955
Inventor 下山晋五百藏忠明森干永樋口珠美
Owner FUJIFILM CORP
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