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Agent for enhancing effect of anticancer agent

A technology for anticancer agents and solvates, which is applied in the field of effect enhancers of anticancer agents, and can solve problems such as predicting pH changes of cancer cells

Pending Publication Date: 2021-05-25
DELTA FLY PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The pH of blood is kept at 7.4 (neutral), so it is also difficult to predict the pH change of the microenvironment around cancer cells from the pH change of blood in terms of pharmacokinetics
It is known that pH changes in the microenvironment around cancer cells can be estimated from pH changes in urine (Non-Patent Document 6 and Patent Document 1), but it is difficult to provide direct evidence of pH changes in the microenvironment around cancer cells

Method used

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  • Agent for enhancing effect of anticancer agent
  • Agent for enhancing effect of anticancer agent
  • Agent for enhancing effect of anticancer agent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0100] [Example 1] Changes in pH of urine caused by taking citrates

[0101] After administering citrates to men (70 years old) with acidic urine at the following doses, changes in pH of urine were measured over time.

[0102] (Usage · Dosage)

[0103] (1) Take 6 tablets (3 g) of 500 mg potassium citrate sodium citrate hydrate tablet (Uralyt (Nippon Chemifa Co., Ltd.)) once a day after a meal

[0104] (2) Take sodium bicarbonate salt of the main active metabolite of potassium citrate and sodium citrate hydrate (500 mg sodium bicarbonate tablet "Mylan" (Mylan Pharmaceuticals)) 6 times a day after a meal slice (3g)

[0105] (result)

[0106] The measurement results of the pH of urine after taking citrates are shown in figure 1 . By orally ingesting 6 tablets (3 g) of 500 mg tablets of potassium citrate sodium citrate hydrate (Uralyt compound tablet (Nippon Chemifa Co., Ltd.)) once / day after a meal, the pH of urine is alkalized to obtain maintain.

[0107] On the other han...

Embodiment 2

[0108] [Example 2] Changes in the concentration of bicarbonate in blood and urine caused by taking citrates

[0109] Potassium citrate and lemon in the blood when 50 mg of potassium citrate and sodium citrate hydrate powder (Uralyt-U compound powder (Nippon Chemifa Co., Ltd.)) were orally administered to mice for cancer cell transplantation were measured over time. The concentration of the active metabolite (bicarbonate) of sodium bicarbonate hydrate, the results are shown in figure 2 (A).

[0110] In addition, the concentration of the active metabolite (bicarbonate) of the urine of potassium citrate and sodium citrate hydrate and the pH of the urine were measured over time in the urine of the mice after administration, and the results are shown in figure 2 (B), and figure 2 (C).

[0111] The above results show that the concentration change of the active metabolite (bicarbonate) of potassium citrate and sodium citrate hydrate in urine is well linked with the pH change of...

Embodiment 3

[0113] [Example 3] Enhanced effect of anticancer agents due to administration of citrates

[0114] To tumor-bearing mice (a model in which B16 mouse melanoma cells were subcutaneously transplanted), (1) administration of mouse anti-PD-1 antibody (Bio X Cell, BE0146) (5 mg / kg), (2) citric acid Administration of potassium sodium citrate hydrate compound powder (Uralyt-U compound powder (Japan Chemifa Co., Ltd.)) (10 mg / day or 30 mg / day / mouse (oral)), or (3) anti- Compound powder of PD-1 antibody (5 mg / kg) and potassium citrate-sodium citrate hydrate (Uralyt-U compound powder (Nippon Chemifa Co., Ltd.)) (10 mg / day or 30 mg / day / mouse (oral) ) were administered in combination, and the tumor volume and the body weight of the mice were measured over time. Potassium citrate-sodium citrate hydrate was administered daily, and the anti-PD-1 antibody was intraperitoneally administered only once at a dose of 5 mg / kg / day on the day after the day of cell transplantation (day 1).

[0115] S...

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Abstract

The present invention relates to a pharmaceutical composition that contains a citrate used to enhance the effect of an anticancer agent.

Description

technical field [0001] The present invention relates to an effect enhancer of an anticancer agent, a method for determining the effect increase, and related medical tools. Background technique [0002] In the treatment of conventional anticancer agents, which emphasize the shrinkage of cancer, it is not uncommon to be accompanied by side effects that seriously affect the health of cancer patients. Antibody drugs related to cancer molecular targeting drugs and cancer immunotherapy are mostly expensive, and they have become a serious social problem among elderly cancer patients and the weak in society, which have gradually increased in recent years. [0003] In recent years, diagnostic drugs that predict the effects of cancer immunotherapy agents, cancer molecular targeting drugs, and cancer chemotherapeutic agents have been developed and clinically applied, but they are expensive, and medical expenses are expected to continue in the future along with drug costs Increase. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61P35/00A61K47/12A61K31/138A61K31/282A61K31/337A61K31/513A61K31/519A61K31/7068
CPCA61B5/00A61B5/145A61F13/42A61F13/49A61F13/84A61K31/191A61K39/00A61P35/00G01N33/84A61K31/138A61K31/337A61K31/513A61K47/12A61K31/282A61K31/7068A61K31/519A61K31/194C07K2317/76C07K16/2818A61K39/3955A61K2039/505A61K2300/00A61F13/49007A61B5/4848A61B5/6808G01N2800/52A61F2013/427A61F2013/8473
Inventor 和田洋巳石田龙弘江岛清
Owner DELTA FLY PHARMA