Application of sodium phenylbutyrate and metabolites thereof in preparation of medicine for preventing or treating chemotherapy-induced peripheral neuropathic pain

A metabolite, sodium phenylbutyrate technology, applied in the field of medicine to achieve the effect of increasing the threshold of mechanical pain paw withdrawal, significant analgesic effect, and improving demyelination

Pending Publication Date: 2021-11-23
ZHAOKE PHARMA GUANGZHOU
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the role of neurotrophic drugs in the treatment of taxane-induced paresthesia peripheral neuropathy is still controversial, there are some clinical therapeutic effects

Method used

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  • Application of sodium phenylbutyrate and metabolites thereof in preparation of medicine for preventing or treating chemotherapy-induced peripheral neuropathic pain
  • Application of sodium phenylbutyrate and metabolites thereof in preparation of medicine for preventing or treating chemotherapy-induced peripheral neuropathic pain
  • Application of sodium phenylbutyrate and metabolites thereof in preparation of medicine for preventing or treating chemotherapy-induced peripheral neuropathic pain

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] The effect of embodiment 1 sodium phenylbutyrate on general state of mice

[0033] 1.1 Modeling

[0034] Female C57BL / 6 mice were injected intraperitoneally with paclitaxel, 4.5mg / kg, once every other day, for a total of 4 injections (1, 3, 5, 7d) to establish chemotherapy-induced peripheral neuralgia (CIPN) in mice Model, normal control group animals were injected with normal saline.

[0035] 1.2 Experimental design

[0036] Group design: normal control group, model control group, ZK034 low-dose group, ZK034 middle-dose group, ZK034 high-dose group and pregabalin group;

[0037] See the table below for specific grouping information:

[0038]

[0039]

[0040] Note: The first digit of the animal number represents the group (1, 2, 3, 4, 5 and 6 represent the normal control group, model control group, ZK034 low-dose group, ZK034 middle-dose group, ZK034 high-dose group and pregabalin respectively Group). The second letter represents gender (F is female), the la...

Embodiment 2

[0055] The effect of embodiment 2 sodium phenylbutyrate on mouse body weight

[0056] 2.1 Modeling is the same as in Example 1

[0057] 2.2 The experimental design is the same as in Example 1.

[0058] 2.3 Administration information is the same as that in Example 1.

[0059] 2.4 Body weight determination

[0060] Measurement time: 2 times a week;

[0061] Measuring animals: all surviving experimental animals planned to be measured.

[0062] 2.5 Statistics are the same as in Example 1.

[0063] 2.6 Test results

[0064] Throughout the test ( figure 1 , Table 1), the weight of the animals in the normal control group was increasing, and the overall change trend of the body weight of the animals in the other groups was the same. After the drug intervention, there was no significant effect on the change of the body weight of the animals. in figure 1 The data in the table are expressed as mean ± standard error (Mean ± SEM), and each test group uses 10 animals for statistical...

Embodiment 3

[0068] Example 3 Effect of sodium phenylbutyrate on the paw withdrawal threshold of mice with mechanical pain

[0069] 3.1 Modeling is the same as in Example 1

[0070] 3.2 The experimental design is the same as in Example 1.

[0071] 3.3 Administration information is the same as that in Example 1.

[0072] 3.4 Determination of mechanical pain withdrawal threshold (MWT)

[0073] Measurement time: 1 test before modeling, 7d, 14d, 20d, 25d, 30d after modeling;

[0074] Measuring animals: all surviving experimental animals that are planned to be measured;

[0075] Measuring method: Before testing, the animals were first put into the testing box to adapt for 3 consecutive days, 30 minutes per day; each time the animal was put into the testing box to adapt to 10 minutes before testing, each animal was tested 3 times in a row to get the average value, and each interval 5min.

[0076] 3.5 Statistics are the same as in Example 1.

[0077] 3.6 Test results

[0078] The average m...

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Abstract

The invention discloses application of sodium phenylbutyrate and metabolites thereof in preparation of a medicine for preventing or treating chemotherapy-induced peripheral neuropathic pain. Animal experiments prove that the sodium phenylbutyrate has a remarkable analgesic effect on paclitaxel-induced peripheral neuropathic pain of a mouse, the mechanical pain foot retraction threshold value of the mouse can be obviously increased, the photo-thermal pain foot retraction incubation period of the mouse is obviously prolonged, and the condition of demyelination of medullary nerve fibres in sciatic nerves of the mouse caused by paclitaxel is improved. The sodium phenylbutyrate can be used for preparing the medicine for preventing or treating chemotherapy-induced peripheral neuropathic pain, has no obvious toxic or side effect, and has a good application prospect.

Description

technical field [0001] The invention belongs to the field of medicines, in particular to the application of sodium phenylbutyrate and metabolites thereof in the preparation of medicines for preventing or treating peripheral nerve pain caused by chemotherapy. Background technique [0002] Chemotherapy-induced peripheral neuropathy (CIPN) is the damage caused by chemotherapy drugs to peripheral nerve function, as well as a series of symptoms and signs of neurological dysfunction. Peripheral neurotoxicity is a common dose-limiting toxicity of chemotherapy drugs. An increase in the dose of chemotherapy drugs can lead to peripheral neuritis, which generally manifests as symmetrical, sensory disturbances starting from the fingers (toes), conscious numbness, and aggravated by cold. As the disease progresses, it can be manifested as loss of touch, pressure, vibration, and extremity extremities, tendon reflexes, etc., and needle-like pain. [0003] Peripheral neurotoxicity is usuall...

Claims

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Application Information

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IPC IPC(8): A61K31/192A61P25/02
CPCA61K31/192A61P25/02
Inventor 戴向荣李小羿陈程殷雷
Owner ZHAOKE PHARMA GUANGZHOU
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