Application of rhodophylline and / or rhodophylline salt in preparation of anti-anxiety drug

Abstract

The invention relates to application of rhodophylline and / or rhodophylline salt in preparation of an anti-anxiety drug, and belongs to the technical field of biological medicine. According to the invention, an active component, namely the rhodophytic acid, or a salt-forming form of the rhodophytic acid is added into an ointment matrix or a gel matrix to prepare ointment or gel, wherein the mass percentage content of the rhodophytic acid in the ointment or the gel is 0.5-1%. The external preparation disclosed by the invention has a quick-acting anti-anxiety effect, and is good in safety and free from addiction.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and more specifically, relates to the use of kainic acid and / or kainic acid salts in the preparation of antianxiety drugs. Background Art

[0002] Anxiety disorder is the most common mental disorder among Chinese residents, with a lifetime prevalence of 7.57%. It is characterized by excessive tension, fear or panic attacks without clear targets and causes, and is often accompanied by symptoms such as increased heart rate and difficulty sleeping. Its biological mechanism has not yet been fully elucidated. Currently, the drugs used in clinical treatment of anxiety disorders mainly include benzodiazepines or SSRI antidepressants, both of which are administered orally. Benzodiazepines take effect quickly, but have side effects such as addiction, drowsiness, and motor impairment. SSRI antidepressants take effect slowly and have more serious side effects such as gastrointestinal reactions and sexual dysfunction. Summary of the invention

[0003] The present invention provides the use of kainic acid and / or kainic acid salt in the preparation of antianxiety drugs, wherein kainic acid and / or kainic acid salt activate the cold receptor GluK2 of peripheral tissue nerve endings and the downstream cold perception center to produce a fast-acting antianxiety effect. Compared with oral SSRI antidepressants, the antianxiety onset time of the present invention is faster; compared with benzodiazepine drugs, the present invention has good safety, no addiction, and good tolerance.

[0004] According to the purpose of the present invention, there is provided the use of kainic acid and / or kainic acid salt in the preparation of antianxiety drugs.

[0005] Preferably, the kainic acid and / or kainic acid salt is used to activate the cold receptor GluK2 of peripheral tissue nerve endings and the downstream cold perception center, thereby producing anxiolytic effect.

[0006] Preferably, the kainic acid and / or kainic acid salt is added to a matrix to prepare an ointment preparation for external use on the skin or a gel preparation for external use on the skin.

[0007] Preferably, in the skin external ointment preparation or skin external gel preparation, the mass percentage content of kainic acid and / or kainic acid salt is 0.5%-1%.

[0008] Preferably, the ointment base of the skin external ointment preparation is selected from one or more of beeswax, paraffin, vaseline, liquid paraffin, wool wax, silicone, stearic acid, dimethicone, and isooctyl palmitate.

[0009] Preferably, the base of the skin external gel preparation is selected from carbomer or sodium alginate.

[0010] In general, the above technical solution conceived by the present invention has the following technical advantages compared with the prior art:

[0011] (1) Compared with oral SSRI antidepressants, the antianxiety effect of the present invention is faster. Clinically, oral SSRI drugs take more than 3 weeks to take effect, while the onset time in this experiment is 1 hour.

[0012] (2) Compared with benzodiazepines, the present invention has good safety, no addiction, and good tolerance. Clinically, oral benzodiazepines have a certain degree of addiction, while the present drug is an edible amino acid substance and is for external use, so it will not produce addiction.

[0013] (3) The present invention has no gastrointestinal irritation.

[0014] (4) The present invention has a simple production process, is easy to transport and carry, and is convenient to use. DETAILED DESCRIPTION

[0015] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. In addition, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0016] Overactivity of the anterior cingulate cortex may be an important biological mechanism causing anxiety disorders. In recent years, our team has conducted a lot of basic research work and found that the neural circuit mechanism mediating cold perception plays an important role in the regulation of anxiety behavior. Brief single cold exposure can activate the excitatory projection of oxytocin neurons from the median preoptic nucleus of the hypothalamus to the paraventricular nucleus, prompting the release of oxytocin and acting on inhibitory interneurons in the anterior cingulate cortex, inhibiting the activity of the anterior cingulate cortex and producing an anti-anxiety effect. The cold receptor distributed in the nerve endings of peripheral tissues such as the skin, the kainate-type glutamate receptor GluK2, is a key target for mediating the anti-anxiety effect of cold perception. The topical application of kainic acid and / or kainic acid salts to the skin can activate the GluK2 receptor and produce an anti-anxiety behavioral effect.

[0017] The preparation process of the external preparation of the present invention comprises: heating and melting matrix components such as beeswax, paraffin, vaseline, etc. in a water bath to form a solution A, cooling the solution A to 45°C-60°C, weighing kainic acid according to a mass percentage of 0.5%-1% and adding it to the solution A, mixing and then packaging and cooling to obtain an ointment preparation; or weighing carbomer or kelp, adding ultrapure water equivalent to 25-50 times of the mass of the carbomer or kelp, and fully stirring to prepare a gel matrix, weighing kelp, adding ultrapure water to prepare a 5% kelp solution (aqueous phase), and adding the aqueous phase to the gel matrix according to a mass ratio of the aqueous phase to the gel matrix of 1:5-1:10 to obtain a gel preparation.

[0018] Example 1

[0019] Prescription composition: 0.01g kainic acid, 0.3g beeswax, 0.3g paraffin, and 1.4g vaseline.

[0020] First, weigh 0.3 g of beeswax, 0.3 g of paraffin, and 1.4 g of vaseline, put them in a container, heat to 110°C to melt to remove moisture, filter while hot and cool to 65°C-70°C, add 0.01 g of kainic acid and stir evenly until completely dissolved, and can at 45°C-60°C to obtain an ointment preparation.

[0021] Example 2

[0022] Prescription composition: 0.01g kainic acid, 2.5g sodium alginate.

[0023] First, 0.01 g of kainic acid was weighed and dissolved in 20 ml of sterile ultrapure water to obtain solvent A. 2.5 g of sodium alginate was weighed and added to 80 ml of sterile ultrapure water, and stirred overnight to fully swell the alginate to obtain a gel matrix. Solvent A was added to the gel matrix to obtain a gel preparation.

[0024] Example 3: Investigate the antianxiety effect of the external preparation of the present invention.

[0025] The drug prepared by the method of Example 1 was used, and an empty ointment preparation with the same components (beeswax, paraffin, vaseline) was selected as the control group. The experimental animals were 8-week-old C57BL / 6J mice (31), weighing 20±3g, purchased from Hunan Slake Jingda Experimental Animal Company. They were randomly divided into a solvent group and a kainic acid preparation group, and all the hair on the back from the neck to the tail of the mice was shaved off, and the control preparation or the kainic acid preparation was applied to the exposed skin respectively. Open field and elevated plus maze tests were performed 1 hour later. The results are shown in Tables 1 and 2.

[0026] Table 1 Effects of kainic acid topical preparations on open field test in mice

[0027]

[0028] Table 2 Effects of kainic acid topical preparation on elevated plus maze test in mice

[0029]

[0030] T test was used to determine the difference between the control group and the kainic acid preparation group. The results showed that compared with the control group, the time taken by the kainic acid preparation group to enter the open arm of the elevated plus maze was significantly prolonged (p<0.01). External application of 5‰ kainic acid preparation also significantly increased the number of times mice entered the open arm (p<0.05) and the distance they moved in the open arm (p<0.01).

[0031] Compared with the control group mice, the topical kainic acid preparation increased the mice's residence time in the central area of ​​the open field (p<0.05), but there was no significant difference in the total movement distance between the two groups of mice, that is, the topical kainic acid preparation did not affect the mice's exercise ability.

[0032] The above results show that the external preparation of the present invention can produce antianxiety-like effects.

[0033] It will be easily understood by those skilled in the art that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. Use of kainic acid and / or kainic acid salts in the preparation of antianxiety drugs.

2. The use according to claim 1, characterized in that The kainic acid and / or kainic acid salt is used to activate the cold receptor GluK2 of peripheral tissue nerve endings and the downstream cold perception center, thereby producing an anti-anxiety effect.

3. The use according to claim 1 or 2, characterized in that: The kainic acid and / or kainic acid salt is added into a matrix to prepare an external ointment preparation or an external gel preparation for skin.

4. The use according to claim 3, characterized in that In the skin external ointment preparation or skin external gel preparation, the mass content of kainic acid and / or kainic acid salt is 0.5%-1%.

5. The use according to claim 3, characterized in that The ointment base of the skin external ointment preparation is selected from one or more of beeswax, paraffin, vaseline, liquid paraffin, wool wax, silicone, stearic acid, dimethyl silicone oil, and isooctyl palmitate.

6. The use according to claim 3, characterized in that The base of the skin external gel preparation is selected from carbomer or sodium alginate.

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