KR102285938B1 - Composition for treating or preventing chemotheapy-induced peripheral neuropathy comprising imatinib or pharmaceutically acceptable salts thereof as active ingredient - Google Patents

Abstract

The present invention provides a pharmaceutical composition for preventing or treating chemotherapy-induced peripheral neuropathy comprising imatinib or a pharmaceutically acceptable salt thereof, which has been conventionally used as a therapeutic agent for chronic myelogenous leukemia, as an active ingredient, and the composition using the composition. It relates to a method for preventing or treating a disease, and not only provides a new use of imatinib, but also effectively prevents or treats chemotherapy-induced peripheral neuropathy, so it can be widely used in the development of new therapeutic agents for chronic pain diseases.

Description

A composition for treating or preventing chemotheapy-induced peripheral neuropathy comprising imatinib or pharmaceutically acceptable salts thereof as active ingredient, comprising imatinib or a pharmaceutically acceptable salt thereof as an active ingredient

The present invention relates to a composition for preventing or treating peripheral neuropathy induced by a drug comprising imatinib or a pharmaceutically acceptable salt thereof as an active ingredient, and more specifically, the present invention relates to a conventional therapeutic agent for chronic myelogenous leukemia. A pharmaceutical composition for the prevention or treatment of peripheral neuropathy induced by a drug containing imatinib or a pharmaceutically acceptable salt thereof as an active ingredient, and a pharmaceutical composition for peripheral neuropathy induced by a drug using the composition It relates to a method of treatment or prevention.

Chemotherapy-Induced Peripheral Neuropathy (CIPN), which is one of the side effects of chemotherapy, can be defined as damage, inflammation, and degeneration of peripheral nerve fibers. Symptoms of drug-induced peripheral neuropathy include movement and sensory nerve-related symptoms such as tingling, numbness, burning, stabbing, and tingling in the fingers and toes. There are shooting and pricking, which are usually bilateral, and the lower extremities are more severe. Symptoms may worsen to the point of pain and may progress to loss of deep tendon reflexes, loss of vibration, temperature, touch, and position. , in some cases it may get worse and may remain irreversible.

Drug-induced peripheral neuropathy can be caused by a variety of causes, including genetics, chronic diseases, environmental toxins, alcoholism, nutritional deficiencies, and drugs. For cancer patients who experience drug-induced peripheral neuropathy, it is known that the chemotherapy they received is the cause, and it is generally related to the cumulative dose of the anticancer drug used. In the case of chemotherapy, CIPN can occur in about 25%, and the degree of CIPN depends on the type of chemotherapy, the administered dose, and the cumulative dose. There is a high risk of occurrence in patients with

Anticancer agents that induce peripheral neuropathy include platinum-based drugs such as cisplatin, carboplatin, and oxaliplatin, paclitaxel, docetaxel, and vinca alkaloids. In addition to vincristine, vinorelbine, and others, etoposide, methotrexate, thalidomide, bortezomib, and the like. A standard prophylaxis or treatment method for peripheral neuropathy induced by drugs has not yet been established. Research using glutathione, vitamin E, amifostine, glutamine, glutamate, calcium/magnesium, etc. as a preventive method for drug-induced peripheral neuropathy However, the evidence is still insufficient. Currently, tricyclic antidepressants, anticonvulsants (carbamazepine, gabapentin), venlafaxine, and opioid analgesics are used in clinical practice to relieve pain symptoms, but they are often not effectively controlled. . As such, various drugs for preventing and treating CIPN have been studied so far, but many of the therapeutic agents used show limitations in efficacy. Dosage adjustment or discontinuation is the only way to prevent.

Under this background, the present inventors made intensive efforts to find substances for treating peripheral neuropathy induced by drugs. As a result, imatinib or a pharmaceutically acceptable salt thereof, which was conventionally used as a therapeutic agent for chronic myelogenous leukemia, is membrane voltage dependent. It can reduce the expression of sodium ion channel 1.8 (Nav1.8), so it was confirmed that imatinib or a pharmaceutically acceptable salt thereof can be used as a prophylactic or therapeutic agent for peripheral neuropathy induced by drugs, and the present invention completed.

One object of the present invention is to provide a pharmaceutical composition for preventing or treating peripheral neuropathy induced by a drug comprising imatinib or a pharmaceutically acceptable salt thereof as an active ingredient.

Another object of the present invention is to provide an anticancer adjuvant for the prevention or treatment of peripheral neuropathy induced by a drug, comprising the pharmaceutical composition.

Another object of the present invention is to provide a method for preventing or treating peripheral neuropathy induced by drugs using the composition.

However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problems, and other problems not mentioned will be clearly understood by those skilled in the art from the following description.

In order to achieve the above object, the present invention

It provides a pharmaceutical composition for preventing or treating peripheral neuropathy induced by a drug comprising imatinib or a pharmaceutically acceptable salt thereof as an active ingredient.

In one embodiment of the present invention, the drug may be any one or more selected from the group consisting of cisplatin, carboplatin, oxaliplatin, paclitaxel, docetaxel, vincristine, vinorelbine, etoposide, methotrexate, thalidomide, and botezomib.

In one embodiment of the present invention, the pharmaceutically acceptable salt of imatinib may be imatinib mesylate.

In another embodiment of the present invention, the composition may relieve pain caused by the peripheral neuropathy.

In addition, the present invention provides an anticancer adjuvant for the prevention or treatment of peripheral neuropathy induced by a drug, comprising the pharmaceutical composition.

In one embodiment of the present invention, the anticancer adjuvant may be administered in combination with an anticancer agent.

In another embodiment of the present invention, the anticancer adjuvant may be administered simultaneously (simultaneous), separately (separate) or sequentially (seqeuntial).

In addition, the present invention provides a method for preventing or treating peripheral neuropathy induced by a drug, comprising administering the composition to a subject.

In addition, the present invention provides the use of the composition for the prevention or treatment of peripheral neuropathy induced by the drug.

In addition, the present invention provides a method for preventing or treating peripheral neuropathy induced by a drug, comprising administering the adjuvant to a subject.

In addition, the present invention provides a use for preventing or treating peripheral neuropathy induced by the medicament of the adjuvant.

The pharmaceutical composition for preventing or treating chemotherapy-induced peripheral neuropathy of the present invention includes imatinib, which has been used as a conventional treatment for chronic myelogenous leukemia, as an active ingredient, and provides a new use of imatinib as well as chemotherapy-induced chemotherapy. Since peripheral neuropathy can be effectively treated or prevented, it can be widely used in the development of new therapeutic agents for chronic pain diseases.

1 shows a schematic diagram of a method for preparing an animal model of chemotherapy-induced peripheral neuropathy by administering vincristine to the abdominal cavity of a mouse (C57BL/6 mouse).
Figure 2 relates to the results of confirming whether peripheral neuropathy is induced in the experimental group and the control group administered with vincristine. , FIG. 2c shows the results of measuring the weight change of the experimental group and the control group, and FIG. 2d shows the results of measuring the exercise ability change of the experimental group and the control group.
Figure 3 relates to the tissue findings of the experimental group and the control group administered with vincristine, Figure 3a shows the results of H&E staining of the plantar tissue sample, Figure 3b shows the results of measuring the skin thickness of the plantar tissue, Fig. 3c shows the result of measuring the number of H&E-positive inflammatory cells.
Figure 4 relates to the results of comparison of the mRNA and protein amounts of Nav1.7 and Nav1.8 expressed in an animal model of peripheral neuropathy by administration of vincristine, and Figure 4a is Nav1.7 and Nav1.8 proteins in the experimental group and the control group. shows the results of measuring the expression and relative amounts of mRNA, and FIG. 4b shows the expression of Nav1.7 and Nav1.8 proteins and normalized mRNA levels in the experimental group and the control group.
FIG. 5 relates to the results of immunohistochemical staining of dorsal root ganglion neurons of the spinal cord. FIG. 5a shows the results of confirming the increase in Nav1.8 in an animal model of peripheral neuropathy by vincristine administration by histological findings, and FIG. 5b is It shows the result of confirming whether Nav1.8 was increased by targeting Nav1.8 peripherin.
6 shows the results of measuring the pain improvement effect of imatinib mesylate according to the administration method of the present invention.
7 shows an increase in Nav1.8 and a blocking effect of Nav1.8 by imatinib mesylate in an animal model of peripheral neuropathy by administration of vincristine.
8 shows the pain relief effect of high concentration imatinib mesylate (50 mg/kg) after peripheral neuropathy caused by administration of vincristine.
9 shows the pain reduction effect of high concentration imatinib mesylate (50 mg/kg) over time.
Figure 10 shows the blocking effect of Nav1.8 current by imatinib mesylate (10 uM).

Hereinafter, the present invention will be described in detail.

The present inventors conducted various studies related to the treatment of drug-induced peripheral neuropathy, and as a result of administering imatinib mesylate to an animal model in which peripheral neuropathy was induced by vincristine, the threshold for mechanical pain was lowered. By confirming the restoration to normal, the present invention was completed.

Accordingly, the present invention provides a pharmaceutical composition for preventing or treating peripheral neuropathy induced by a drug comprising imatinib or a pharmaceutically acceptable salt thereof as an active ingredient. The pharmaceutically acceptable salt of imatinib according to the present invention may be imatinib mesylate. In addition, the drug according to the present invention is cisplatin, carboplatin, oxaliplatin, paclitaxel, docetaxel, vincristine, vinorelbine, etoposide ( etoposide), methotrexate, thalidomide, and bortezomib may be at least one selected from the group consisting of.

"Drug-induced peripheral neuropathy", a disease targeted by the present invention, is a disease in which peripheral inflammation is generated by administration of an anticancer drug and chronic pain is caused by the action of various inflammation-related cytokines. It refers to a disease that causes persistent chronic pain by increasing the occurrence of pain due to changes in excitability through changes in the ion channels of sensory neurons, etc.

In the present invention, the anticancer agent known as the cause of peripheral neuropathy induced by the drug is cisplatin, carboplatin, platinum such as oxaliplatin, paclitaxel, docetaxel, etc. ) and other vinca alkaloids such as vincristine and vinorelbine, etoposide, methotrexate, thalidomide, or botezomib ( bortezomib), but is not limited thereto.

As used herein, the term "imatinib" is chemically 4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-((4-pyridin-3-yl)pyri Midin-2-yl-amino)phenyl]-benzamide (4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-((4-pyridin-3-yl)pyrimidin-2-yl -amino)phenyl]-benzamide)). The imatinib is known as a therapeutic agent for treating chronic myelogenous leukemia by specifically inhibiting the activity of tyrosine kinase by binding to the ATP binding site of tyrosine kinase whose expression is induced by the Bcr-Abl gene, and its pharmaceutically acceptable Imatinib mesylate, a kind of salt, is sold under the trade name of Gleevec(TM), Novartis Pharmaceuticals, USA. In addition, other types of tyrosine such as platelet-derived growth factor receptor beta (PDGF-beta), Akt (protein kinase B), extracellular regulatory kinases 1 and 2 (ERK 1 and ERK2), c-kit, etc. It is also known to exhibit inhibitory effects on kinases.

In one embodiment of the present invention, vincristine was intraperitoneally injected to induce peripheral neuropathy in mice, and at the same time, imatinib mesylate was injected into each mouse at two concentrations (1 mg/kg, 10 mg/kg). As a result, it was confirmed that peripheral neuropathy was not observed at both low and high concentrations, and it was confirmed that sensitivity to mechanical pain did not appear even after vincristine and imatinib mesylate treatment were stopped (see Example 2-1).

In another embodiment of the present invention, as a result of injecting imatinib mesylate into mice after peripheral neuropathy was caused by administration of vincristine, it was confirmed that high concentration (50 mg/kg) of imatinib mesylate relieved pain ( see Example 2-2).

The above results suggest that the composition according to the present invention comprising imatinib or a pharmaceutically acceptable salt thereof can be usefully used as a preventive or therapeutic agent for peripheral neuropathy induced by an anticancer agent. In addition, it suggests that it can be used as an anticancer adjuvant composition for suppressing the side effects of anticancer drugs.

As used herein, the term “pharmaceutically acceptable salt” refers to a salt in a form that can be used pharmaceutically among salts, which are substances in which a cation and an anion are bonded by electrostatic attraction, usually with a metal salt, an organic base and salts, salts with inorganic acids, salts with organic acids, salts with basic or acidic amino acids, and the like. For example, the metal salt may be an alkali metal salt (sodium salt, potassium salt, etc.), alkaline earth metal salt (calcium salt, magnesium salt, barium salt, etc.), an aluminum salt or the like; Salts with organic bases include triethylamine, pyridine, picoline, 2,6-lutidine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine, dicyclohexylamine, N,N-dibenzylethylenediamine salts with, etc.; salts with inorganic acids may be salts with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, and the like; Salts with organic acids may be salts with formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and the like; Salts with basic amino acids may be salts with arginine, lysine, ornithine and the like; The salt with an acidic amino acid may be a salt with aspartic acid, glutamic acid, or the like.

For the purposes of the present invention, the pharmaceutically acceptable salt is an acid addition salt or a base addition salt of imatinib suitable for the treatment of patients who are expected to develop peripheral neuropathy induced by the drug or have the disease. However, it is not particularly limited thereto.

As used herein, the term "prevention" refers to a pharmaceutical composition comprising, as an active ingredient, imatinib or a pharmaceutically acceptable salt thereof provided by the present invention to an individual who is expected to develop peripheral neuropathy and chronic pain induced by a drug. It means any action that inhibits or delays the onset of the disease by administering it.

As used herein, the term “treatment” refers to any action that clinically intervenes to alter the natural process of an individual or cell to be treated, and may be performed during the course of a clinical pathology or to prevent it. The desired therapeutic effect includes preventing the occurrence or recurrence of a disease, alleviating symptoms, reducing any direct or indirect pathological consequences of the disease, preventing metastasis, reducing the rate of disease progression, and alleviating the disease state. or temporary relief, remission and improvement of prognosis. For the purpose of the present invention, the treatment is induced by the drug by administering a pharmaceutical composition comprising imatinib or a pharmaceutically acceptable salt thereof as an active ingredient to a patient who has developed peripheral neuropathy and chronic pain induced by the drug. It may be construed to include all actions that improve the course of peripheral neuropathy, but is not particularly limited thereto.

In addition, as another aspect of the present invention, the present invention provides an anticancer adjuvant comprising imatinib or a pharmaceutically acceptable salt thereof as an active ingredient. In this case, the anticancer adjuvant may be administered simultaneously with the anticancer agent (simultaneous), separately (separate) or sequentially (seqeuntial), and may be administered single or multiple, but is not limited thereto.

On the other hand, the pharmaceutical composition of the present invention may further include an appropriate carrier, excipient or diluent commonly used in the preparation of the pharmaceutical composition. The composition comprising a pharmaceutically acceptable carrier may be in various oral or parenteral formulations. In the case of formulation, it can be prepared using a diluent or excipient such as a filler, extender, binder, wetting agent, disintegrant, surfactant, etc. commonly used. Solid preparations for oral administration may include tablet pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in one or more compounds, for example, starch, calcium carbonate, sucrose or lactose. (lactose), gelatin, etc. can be mixed and prepared.

In addition to simple excipients, lubricants such as magnesium stearate, talc and the like may also be used. Liquid formulations for oral administration include suspensions, internal solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances, and preservatives are included. can Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like can be used.

In addition, the pharmaceutical composition of the present invention is a group consisting of tablets, pills, powders, granules, capsules, suspensions, internal solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations and suppositories It may have any one formulation selected from

On the other hand, as another aspect of the present invention, the present invention is for the prevention or treatment of peripheral neuropathy induced by a drug comprising the step of administering to an individual a composition comprising imatinib or a pharmaceutically acceptable salt thereof as an active ingredient provide a way

As used herein, the term "individual" means all animals, including humans, that are likely to develop or have developed peripheral neuropathy induced by the drug. By administering the composition of the present invention to a subject, it is possible to alleviate or treat peripheral neuropathy induced by drugs.

As used herein, the term "relief" refers to any action in which peripheral neuropathy and chronic pain induced by drugs are improved or beneficial by administration of the composition according to the present invention.

The composition of the present invention is administered in a pharmaceutically effective amount.

In the present invention, the term "administration" refers to introducing the pharmaceutical composition of the present invention to a subject by any suitable method, and the administration route may be administered through various oral or parenteral routes as long as it can reach the target tissue.

The pharmaceutical composition of the present invention may be appropriately administered to a subject according to a conventional method, administration route, and dosage used in the art, depending on the purpose or necessity. Examples of the route of administration may be oral, parenteral, subcutaneous, intraperitoneal, intrapulmonary, and intranasal administration, and parenteral injection includes intramuscular, intravenous, intraarterial, intraperitoneal or subcutaneous administration.

In addition, an appropriate dosage and number of administration may be selected according to methods known in the art, and the amount and frequency of administration of the pharmaceutical composition of the present invention actually administered depends on the type of symptom to be treated, administration route, sex, and health condition. , diet, the age and weight of the individual, and the severity of the disease can be appropriately determined by various factors.

As used herein, the term "pharmaceutically effective amount" means an amount sufficient to suppress or alleviate pain in peripheral neuropathy induced by a drug at a reasonable benefit/risk ratio applicable to medical use, and the effective dose level is Subject type and severity, age, sex, drug activity, sensitivity to drug, administration time, administration route and excretion rate, duration of treatment, factors including concomitant drugs, and other factors well known in the medical field. . The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. and may be administered single or multiple. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect with a minimum amount without side effects, and can be easily determined by those skilled in the art.

Hereinafter, preferred examples are presented to help the understanding of the present invention. However, the following examples are only provided for easier understanding of the present invention, and the contents of the present invention are not limited by the following examples.

Example 1. Preparation and validation of an animal model of drug-induced peripheral neuropathy

1-1. Preparation of an animal model of drug-induced peripheral neuropathy

In order to carry out the experiment according to the present invention, a control group and an experimental group were designed.

An animal model was prepared in the same manner as shown in FIG. 1 . More specifically, the control group administered saline at a dose of 0.1 mg/kg to the abdominal cavity of a mouse (C57BL/6 mouse) for 7 consecutive days, and the experimental group received vincristine at a dose of 0.1 mg/kg for 7 consecutive days. administered for one day.

1-2. Verification of an animal model of drug-induced peripheral neuropathy

In order to confirm whether the peripheral neuropathy-induced animal model (experimental group) was properly made, threshold stimulation was measured using Von Frey after a week in the experimental group.

As a result, as shown in FIGS. 2a and 2b, the response to a threshold stimulus of 1.0 g or more before induction of peripheral neuropathy is reduced to 0.3 g or less, thereby sensitively responding to mechanical pain. It was confirmed that neuropathy occurred.

In addition, as shown in FIG. 2c, weight loss by vincristine was confirmed. However, as shown in FIG. 2d , a decrease in exercise capacity by the anticancer agent was not observed.

In order to confirm whether the peripheral neuropathy-induced animal model (experimental group) was properly made through the presence of peripheral inflammatory findings by anticancer drugs, an experiment was performed to observe the tissue findings by performing H&E staining after obtaining plantar tissue specimens.

As a result, it was confirmed that the thickness of the sole skin increased as shown in FIGS. 3A and 3B .

In addition, as shown in FIG. 3c , it was confirmed that the number of H&E-positive inflammatory cells in the dermis was statistically significantly increased.

1-3. Confirmation of mechanism of increase in pain sensitivity in peripheral neuropathy-induced animal model

In order to confirm the mechanism of increasing pain sensitivity in an animal model of peripheral neuropathy, an experiment was performed to analyze the protein through mRNA analysis or Western blot specifically expressed in pain-related nerve cells when pain is induced by vincristine. did.

As a result, it was confirmed that Nav1.8 mRNA and Nav1.8 protein, which are ion channels of nerve cells involved in pain, were significantly increased in the animal model of induced peripheral neuropathy as shown in FIGS. 4A and 4B . However, it was confirmed that the expression of Nav1.7 mRNA and Nav1.7 protein, which are other pain-related ion channels, did not show significant changes.

In addition, in order to confirm the histologic findings regarding the expression pattern of Nav1.8, immunohistochemical staining of the dorsal root ganglion neurons of the above animal model was performed.

As a result, as shown in FIGS. 5A and 5B , it was confirmed that the expression of Nav1.7 did not increase, but only the expression of Nav1.8 increased.

Summarizing the experimental results, it was confirmed that when vincristine was administered at a dose of 0.1 mg/kg for 7 consecutive days in the abdominal cavity of a mouse, inflammation was induced in the peripheral region and peripheral neuropathy induced by the drug occurred. In addition, through histological findings on the expression pattern of Nav1.8, it was confirmed that the onset of the above-mentioned peripheral neuropathy is related to the expression of Nav1.8.

Example 2. Effects of Imatinib on Drug-induced Peripheral Neuropathy Animal Model

2-1. Imatinib injection simultaneously with induction of peripheral neuropathy

When preparing the animal model in Example 1, imatinib mesylate (Imatinib mesylate, Novatis. SWITZERLAND) was intraperitoneally injected at the same time as the injection of vincristine at doses of 1 mg/kg and 10 mg/kg, respectively, and the two The reaction to mechanical pain was observed in the experimental group.

As a result, as shown in FIG. 6 , it was confirmed that peripheral neuropathy induced by the drug was not observed at both concentrations. In addition, it was confirmed that sensitization to mechanical pain did not occur even after stopping treatment with vincristine and imatinib mesylate.

In addition, an experiment was performed to observe Nav1.8 mRNA in an animal model of chemotherapy (treated only with vincristine) induced peripheral neuropathy and an animal model treated with vincristine and imatinib mesylate simultaneously.

As a result, as shown in FIG. 7 , an increase in Nav1.8 mRNA was confirmed in an animal model of vincristine-induced peripheral neuropathy, but there was no change in Nav1.8 mRNA expression in an animal model treated with vincristine and imatinib mesylate simultaneously. It was confirmed that no

From the above results, it was confirmed that imatinib mesylate blocks pain through a mechanism of suppressing the increase in Nav1.8 expression caused by anticancer drugs.

2-2. Effect of imatinib mesylate after development of drug-induced peripheral neuropathy

After the onset of vincristine-induced peripheral neuropathy (day 8), the pain response was evaluated by intraperitoneal injection of imatinib mesylate in mice.

As a result, as shown in FIG. 8 , it was confirmed that pain was relieved when imatinib mesylate was injected at a high concentration (50 mg/kg). More specifically, as shown in FIG. 9 , it was confirmed that 50 mg/kg of imatinib mesylate was administered, and the pain was blocked from 1 hour, and the pain blocking effect continued for 24 hours.

2-3. Confirmation of the mechanism of alleviation of pain sensitivity in peripheral neuropathy-induced animal models

An experiment was conducted to determine whether Nav1.8 current was blocked in dorsal root sarcomere neurons by high concentration of imatinib mesylate.

As a result, as shown in FIG. 10 , it was confirmed that the Nav1.8 current was blocked by about 50% at 10 uM of imatinib mesylate. In other words, it was confirmed that the blocking of pain caused by anticancer drugs by high concentration of imatinib mesylate was through the blocking mechanism of current through Nav1.8.

Summarizing the above experimental results, it was confirmed that if the anticancer agent and imatinib mesylate were administered at the same time, it was possible to block the pain caused by the anticancer agent in advance. In addition, it was confirmed that the pain already induced by the pre-use of an anticancer agent can be blocked by administering a high concentration of imatinib mesylate. From this, it was confirmed that imatinib mesylate can prevent or treat peripheral neuropathy induced by anticancer drugs.

The above description of the present invention is for illustration, and those of ordinary skill in the art to which the present invention pertains can understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not restrictive.

Claims (7)

Imatinib (4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-((4-pyridin-3-yl)pyrimidin-2-ylamino)phenyl]-benzamide) or a pharmaceutical thereof A pharmaceutical composition for the prevention or treatment of peripheral neuropathy induced by vincristine, comprising as an active ingredient an acceptable salt, wherein the composition relieves pain caused by the peripheral neuropathy. composition to do.
According to claim 1,
The pharmaceutically acceptable salt of imatinib is imatinib mesylate, a pharmaceutical composition for preventing or treating peripheral neuropathy induced by vincristine, characterized in that it is imatinib mesylate.
delete delete An anticancer adjuvant for the prevention or treatment of peripheral neuropathy induced by vincristine, comprising the pharmaceutical composition according to claim 1 .
6. The method of claim 5,
The anti-cancer adjuvant, characterized in that administered in combination with the anti-cancer agent, anti-cancer adjuvant.
7. The method of claim 6,
The combined administration is simultaneous (simultaneous), separately (separate) or sequential (seqeuntial), characterized in that administered as an anticancer adjuvant.

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