阅读说明：本技术 一种化合物在制备疼痛缓解药物中的用途 (Application of compound in preparation of pain relieving medicine ) 是由 孙建波 郭方圆 夏连科 张磊 张震 王泉亮 孙磊博 李波 韩新文 于 2019-08-28 设计创作，主要内容包括：本发明属于药物领域,具体公开了一些化合物在制备疼痛缓解药物中的用途。这些化合物是指铁屎米酮或甲氧蔓菁素以及它们的衍生物,两个物质可以单独使用或联合使用。在给药时,优选为鞘内注射或者静脉注射,在不具备给药条件时,可以通过口服或外用给药。所述化合物对疼痛,尤其是神经病理性疼痛显示出一定的缓解效果。与常见的易成瘾和对中枢神经系统存在严重不良作用的镇痛药物比较,有安全性更高和不易滥用的优点。(The invention belongs to the field of medicines, and particularly discloses application of compounds in preparation of pain relieving medicines. These compounds are fagomine or methoxsulvin and their derivatives, which can be used alone or in combination. When administered, intrathecal injection or intravenous injection is preferable, and when administration conditions are not satisfied, oral administration or external administration is possible. The compounds exhibit some relief effect on pain, especially neuropathic pain. Compared with the common analgesic drugs which are easy to be addicted and have serious adverse effects on the central nervous system, the analgesic drug has the advantages of higher safety and difficult abuse.)

1. Use of a compound for the manufacture of a medicament for pain relief, wherein: the compound is methoxy cyanidin.

2. Use according to claim 1, characterized in that: the pain is neuropathic pain in humans or other mammals.

3. Use according to claim 1, characterized in that: the neuropathic pain is neuropathic pain caused by spinal nerve compression.

4. Use according to claims 1 to 3, characterized in that: the pain relieving medicine is one of oral medicine, external medicine, intrathecal injection medicine and intravenous injection medicine.

5. Use according to claim 4, characterized in that: the pain relief medication is an intrathecal injection medication.

6. Use according to claim 4, characterized in that: the pain relieving medicament is an oral medicament.

7. Use according to claim 4, characterized in that: the pain relieving medicine is an external medicine.

8. Use according to claim 4, characterized in that: the dose of the methoxycynarin is 0.5-40 mg/kg.

Technical Field

The invention belongs to the field of medicines, and particularly relates to application of a compound in preparation of a pain relieving medicine.

Background

Pain is a common sensory symptom, and more or less of the global population suffers from pain of varying degrees. These include visceral pain or body surface pain.

Among the different pains, some are nerve impulse transmission caused by external stimulation, for example, the pain is generated in the case of skin burn, puncture, electrical stimulation, chemical stimulation, etc.; pain in the abdominal cavity and the like are caused by excessive contraction of abdominal muscles. This pain is the normal sensation of external stimuli by the body and is the basis for self-protection and reflex avoidance.

Another type of pain is pain triggered by primary damage and dysfunction of the nervous system, called neuropathic pain, which is inconsistent with external stimuli and can still experience the sensation of pain without external stimuli, typically manifested as spontaneous pain, hyperalgesia, allodynia, and paresthesia. The causes of neuropathic pain include trauma, nerve compression, neuritis, and the like. The general categories, mechanisms and treatment methods of neuropathic pain are described in detail in "expert consensus on neuropathic pain diagnosis and treatment" 2013. Wherein, the nerve damage operation can completely relieve pain, but leads to permanent harms such as numbness of sensation, etc. Most drugs are opiates or similarly acting drugs, which are susceptible to addiction or other psychological harm.

The reported effects of feverfew include protection against myocardial ischemia and ischemia reperfusion injury (Shimingjian, Hulan. protection against myocardial ischemia reperfusion injury in rats, Proc. Pharmacology, 1999, No. 3, page 161 163), resistance to arrhythmia (Shimingjian, Hulan. Effect of feverfew on experimental arrhythmia, No. 1, page 37-39, 2000, Chinese herbal medicine), resistance to infection (Ferreira ME, Nakayama H, de Arias AR, Schinin A, Delbao NV, Senna E, Lagoutte D, Soriano-age n F, Poupnet E, Hocqueller R, Fourraemouthes of thiin-6-alcaloidones Zollone, Schizopylone, Trypanosafenac, Janu J.63, J.29, No. 19, No. 109, No. 11, No. 3, No, in addition, 200780018386.7 reports the use of caribourone for the treatment or prevention of pathologies associated with or caused by mycobacteria. Methoxycyanine has been reported to have an Effect against Trypanosoma cruzi (Chripkova M, Zigo F, Mojzis J. Antiprolific Effect of IndoleHyalexins. Molecules. 2016 Nov 26;21(12). pi: E1626.), against acute and chronic lymphocytic leukemia (Jacob JA, Salmani JM, Chen B. Drugs under preliminary and clinical for the purpose of treatment of both acute and chronic lymphocytic leukemia 2016, 20;10: 1119.), against bacteria, and the like. The compounds are large in quantity and wide in effect, and the research on the effect is not complete.

Disclosure of Invention

In view of the above problems, it is an object of the present invention to provide a medicament with pain relief, which provides more alternatives for administration.

The technical scheme of the invention is as follows:

use of fagomine or methoxsalen in the preparation of a pain relieving medicament.

Wherein the fagomine comprises a derivative of the fagomine, and the methoxyvinum comprises a derivative of the methoxymethylvinum.

Wherein the pain is neuropathic pain in humans or other mammals. .

Wherein the aforementioned neuropathic pain refers to neuropathic pain resulting from nerve compression.

Wherein the aforementioned neuropathic pain refers to neuropathic pain resulting from compression of spinal nerves.

Wherein the pain relieving medicine is one of oral medicine, external medicine, intrathecal injection medicine and intravenous injection medicine.

When intrathecal injection or intravenous injection is selected, the dosage is low, but the administration is inconvenient and requires a specialized physician to perform the administration.

When oral or topical drugs are selected, administration is convenient, but high doses are required.

Wherein the dosage of the fagomine is 0.1-20 mg/kg; the dose of the methoxycyanin is 0.5-40 mg/kg.

Wherein the dose of the fagomine is 0.1-5 mg/kg in intrathecal or intravenous injection; the oral and external dosage is 5-20 mg/kg; the dose of the methoxycynarin is 0.5-10 mg/kg in intrathecal or intravenous injection; the dosage for oral administration and external application is 10-40 mg/kg.

In a model of neuropathic pain caused by spinal nerve compression of a mouse, gavage of 0.1-0.4 mg (about 5-20 mg/kg) of the paediatric ketone mouse and local external application of 0.2-0.8 mg (about 10-40 mg/kg) of the methocyanin mouse show a certain relieving effect on the neuropathic pain, and can be used as a substitute or short-term substitute for other drugs, particularly addictive drugs. Compared with the common analgesic drugs which are easy to be addicted and have serious adverse effects on the central nervous system, the analgesic drug has the advantages of higher safety and difficult abuse. Wherein the fagomine is also called fagomine-6-ketone, and the methoxycyanine is also called 1-methoxycyanine.

Detailed Description

The invention is described in connection with experiments below, and some formulations related to pharmaceutical applications are also provided. The model of spinal nerve ligation of L5 and L6 is used for neuropathic pain, is a model of nerve mechanical injury, has good repeatability and is suitable for mass replication.