Use of a neurotoxin / botox complex for the preparation of a medicament for the treatment of trigeminal neuralgia

Abstract

The application discloses a use of a neurotoxin / botulinum toxin complex in preparation of a medicine for treating trigeminal neuralgia. The neurotoxin / botulinum toxin complex is composed of cobra neurotoxin and botulinum toxin. The neurotoxin / botulinum toxin complex is used in the present application to conduct analgesic effect experiment on a trigeminal neuralgia model. Compared with the botulinum toxin used alone, the neurotoxin / botulinum toxin complex in the present application can significantly improve the pain threshold in the mechanical filament pain threshold in a short time, and prolong the pharmacodynamic time of the analgesic effect.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of medicine, and particularly relates to a use of a neurotoxin / botulinum toxin complex in the preparation of a medicament for treating trigeminal neuralgia. BACKGROUND

[0002] Trigeminal neuralgia is the most common cranial nerve disease, and is mainly manifested as recurrent paroxysmal severe pain in the trigeminal nerve distribution area of one side of the face. The incidence rate is 52.2 / 100,000 in China, and women are slightly more than men. The incidence rate can increase with age. Trigeminal neuralgia often occurs in middle-aged and elderly people, and is more common on the right side than on the left side. The disease is characterized by sudden onset, sudden stop, lightning-like, knife-cutting-like, burning-like, intractable and unbearable severe pain in the trigeminal nerve distribution area of the head and face. Speaking, washing face, brushing teeth or even a slight breeze can cause paroxysmal severe pain. The pain lasts for several seconds or minutes, and the pain is periodic.

[0003] Trigeminal neuralgia is related to pain from the trigeminal nerve, which propagates from the brain and branches to various parts of the face. Trigeminal neuralgia causes severe and recurrent pain in the face, usually on one side. Almost 50% of patients have a trigger zone, and many patients try to avoid stimulation in this area because even light contact there can cause severe pain.

[0004] Although pharmacological treatment or surgical treatment has been used to treat trigeminal neuralgia, there is still limited use due to unsatisfactory efficacy level or side effects. Therefore, there is a need for new drugs with better efficacy. SUMMARY

[0005] The main purpose of the present application is to provide a use of a neurotoxin / botulinum toxin complex in the preparation of a medicament for treating trigeminal neuralgia, so as to overcome the shortcomings of the prior art.

[0006] To achieve the foregoing purposes of the application, the technical solutions adopted by the present application include:

[0007] The present application provides a use of a neurotoxin / botulinum toxin complex in the preparation of a medicament for treating trigeminal neuralgia, wherein the neurotoxin / botulinum toxin complex is composed of cobra neurotoxin and botulinum toxin.

[0008] Further, the neurotoxin includes cobra short-chain neurotoxin cobrotoxin.

[0009] Further, the botulinum toxin includes type A botulinum toxin.

[0010] The embodiment of the present application also provides a product for treating trigeminal neuralgia, characterized in that the product comprises a neurotoxin / botulinum toxin complex.

[0011] Further, the neurotoxin comprises cobra neurotoxin; and the botulinum toxin comprises botulinum toxin type A.

[0012] Compared with the prior art, the present application has the beneficial effect that the neurotoxin / botulinum toxin complex in the present application can significantly improve the pain threshold in the mechanical filament pain threshold in a short time, and prolong the pharmacodynamic time of analgesic effect, compared with the use of botulinum toxin alone. BRIEF DESCRIPTION OF DRAWINGS

[0013] In order to more clearly illustrate the technical solutions of the embodiments of the present application or the prior art, the drawings needed in the embodiment or prior art description will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application, and those skilled in the art can obtain other drawings according to these drawings without creative labor.

[0014] Figures 1a-1b Fig. 1 is a diagram of the analgesic effect of the NTX / BTX complex on the trigeminal neuralgia model in the embodiment 1 of the present application. DETAILED DESCRIPTION

[0015] In view of the defects of the prior art, the present inventors have long-term research and a large number of practices, and have come up with the technical solutions of the present application. The technical solutions of the present application will be described clearly and completely below. Obviously, the described embodiments are only some of the embodiments of the present application, not all. Based on the embodiments of the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0016] Specifically, as one aspect of the technical solutions of the present application, the use of the neurotoxin / botulinum toxin complex in the preparation of a medicament for treating trigeminal neuralgia, the neurotoxin / botulinum toxin complex (denoted as NTX / BTX complex) is composed of cobra neurotoxin and botulinum toxin.

[0017] In some preferred embodiments, the neurotoxin comprises cobra short-chain neurotoxin cobrotoxin, and is not limited thereto.

[0018] In some preferred embodiments, the botulinum toxin comprises botulinum toxin type A, and is not limited thereto.

[0019] In some preferred embodiments, the mass ratio of the neurotoxin to the botulinum toxin is 3 μg / kg:0.2 U.

[0020] In some preferred embodiments, the dosage form of the drug is an injection, without being limited thereto.

[0021] In some preferred embodiments, the neurotoxin / botulinum toxin complex can at least increase the pain threshold of Von Frey mechanical filament pain threshold in a trigeminal neuralgia model.

[0022] In some preferred embodiments, the neurotoxin / botulinum toxin complex can at least advance the onset of analgesia of the botulinum toxin and prolong the analgesia time of the neurotoxin.

[0023] Another aspect of the embodiments of the present application also provides a product for treating trigeminal neuralgia, the product comprising a neurotoxin / botulinum toxin complex.

[0024] In some preferred embodiments, the neurotoxin comprises a cobra neurotoxin (denoted as NTX); and the botulinum toxin comprises a botulinum toxin type A (denoted as BTX).

[0025] In some preferred embodiments, the mass ratio of the neurotoxin to the botulinum toxin is 3 μg / kg:0.2 U.

[0026] In some preferred embodiments, the preparation method of the neurotoxin / botulinum toxin complex comprises: adding a cobrotoxin solution of a cobra short-chain neurotoxin dissolved in physiological saline with a pH of 5 to dissolve the botulinum toxin in a botulinum toxin lyophilized powder, and mixing uniformly by gently shaking, wherein the mass ratio of the cobrotoxin to the botulinum toxin is 3 μg / kg:0.2 U.

[0027] The technical solutions of the present application will be further described in detail below in combination with several preferred embodiments and the accompanying drawings, and the embodiments are implemented on the premise of the technical solutions of the present application, and detailed implementation manners and specific operation processes are given, but the protection scope of the present application is not limited to the following embodiments.

[0028] In the following examples, the experimental materials used in the examples are commercially available from conventional biochemical reagent companies, without being specifically described.

[0029] Example 1

[0030] Analgesic effect of NTX / BTX complex on a trigeminal neuralgia model

[0031] The present embodiment uses eye snake neurotoxin NTX and type A botulinum toxin BTX (i.e. NTX / BTX complex) to conduct analgesic effect experiment on mouse trigeminal neuralgia model. The mass ratio of neurotoxin and botulinus toxin in NTX / BTX complex is 3 μg / kg:0.2 U. In the experiment, distal infraorbital nerve ligation model is used. After modeling, neurotoxin is administered by subcutaneous injection in the back, and botulinus toxin is administered by subcutaneous injection at the operation site. The pain threshold is determined by repeatedly testing the whisker pad with a series of mechanical filaments of different thicknesses. The results are shown in Figures 1a-1b As can be seen from the results, when BTX is used alone, the onset time of increasing pain threshold is slow. When NTX is used alone, although the pain threshold can be increased in a short time, the maintenance effect time is very short. When the complex of the two is used, not only can the pain threshold be significantly increased in a short time, but also the drug effect time can be significantly prolonged, so that the increase in pain threshold is significantly greater than that of botulinus toxin, and the prolongation of drug effect time is significantly better than that of neurotoxin. Figure 1b is Figure 1a As can be seen from the area fitting of each curve in the above table, the NTX / BTX complex in the present application has the advantages of fast onset, long duration and significant analgesic effect.

[0032] In addition, the present inventors have also conducted experiments with other raw materials, process operations and process conditions described in the present specification in reference to the foregoing embodiments, and all have obtained relatively ideal results.

[0033] It should be understood that the technical solutions of the present application are not limited to the above specific implementation cases, and any technical modification made according to the technical solutions of the present application without departing from the purpose of the present application and the scope protected by the claims falls within the protection scope of the present application.

Claims

1. Use of a neurotoxin / botulinum toxin complex in the preparation of a medicament for treating trigeminal neuralgia, wherein the neurotoxin / botulinum toxin complex comprises cobra neurotoxin and botulinum toxin; wherein: The neurotoxin is cobra short-chain neurotoxin cobrotoxin; the botulinum toxin is botulinum toxin type A; the mass ratio of the neurotoxin to the botulinum toxin is 3 μg / kg:0.2U.

2. The use according to claim 1, characterized in that: The dosage form of the medicine is injection.

3. The use according to claim 1, characterized in that: The neurotoxin / botulinum toxin complex can at least increase the pain threshold of the Von Frey mechanical filament pain threshold in the trigeminal neuralgia model.

4. The use according to claim 1, characterized in that: The neurotoxin / botulinum toxin complex can at least enable the analgesic effect of botulinum toxin to occur earlier and prolong the analgesic time of the neurotoxin.

5. A product for treating trigeminal neuralgia, characterized in that: The product includes a neurotoxin / botulinum toxin complex; wherein the neurotoxin is cobra neurotoxin; the botulinum toxin is botulinum toxin type A; and the mass ratio of the neurotoxin to the botulinum toxin is 3 μg / kg:0.2U.

Images