Use of kainic acid and / or kainate for the preparation of anxiolytic medicaments
By activating GluK2 receptors with phycocyanine and/or phycocyanine salts, a topical skin preparation is prepared, which solves the problems of slow onset and obvious side effects of existing anxiety drugs and provides a fast and safe anti-anxiety treatment option.
Patent Information
- Application Number
- CN202411484627.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-23
- Publication Date
- 2026-02-17
- Estimated Expiration
- 2044-10-23
AI Technical Summary
Existing medications for anxiety disorders, such as benzodiazepines and SSRIs, are addictive, have significant side effects, and have a slow onset of action, failing to meet the need for rapid and safe treatment.
By utilizing phycocyanin and/or phycocyanin salts to activate the cold receptors GluK2 and downstream cold sensation centers in peripheral tissue nerve endings, a topical ointment or gel formulation is prepared and applied directly to the skin to produce a rapid anti-anxiety effect.
It achieves rapid-onset anti-anxiety effects, is non-addictive, does not affect the gastrointestinal tract, has good safety, and is simple to produce, making it easy to transport and use.
Smart Images
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Abstract
Description
Technical Field
[0001] This invention belongs to the field of biomedical technology, and more specifically, relates to the application of erythrocyanine and / or erythrocyanine salts in the preparation of anti-anxiety drugs. Background Technology
[0002] Anxiety disorders are the most prevalent mental disorder among Chinese residents, with a lifetime prevalence as high as 7.57%. They are primarily characterized by excessive tension, fear, or panic attacks without a clear object or cause, often accompanied by symptoms such as rapid heart rate and difficulty sleeping. Their biological mechanisms are not yet fully understood. Currently, the main medications used clinically to treat anxiety disorders include benzodiazepines or SSRIs (antidepressants administered orally). Benzodiazepines have a faster onset of action but have side effects such as addiction, drowsiness, and impaired motor function. SSRIs have a slower onset of action and have more severe side effects such as gastrointestinal reactions and sexual dysfunction. Summary of the Invention
[0003] This invention provides the application of phycocyanin and / or phycocyanin salts in the preparation of anti-anxiety drugs. Phycocyanin and / or phycocyanin salts produce a rapid-onset anti-anxiety effect by activating the cold receptor GluK2 in peripheral tissue nerve endings and downstream cold sensation centers. Compared with oral SSRI antidepressants, the anti-anxiety effect of this invention is faster; compared with benzodiazepines, this invention has better safety, no addictive properties, and good tolerability.
[0004] According to the present invention, the use of phycocyanine and / or phycocyanine salts in the preparation of anxiolytic drugs is provided.
[0005] Preferably, the eolycanine and / or eolycanine salts are used to produce an anti-anxiety effect by activating the cold receptor GluK2 in peripheral tissue nerve endings and the downstream cold perception center.
[0006] Preferably, the erythrocyanine and / or erythrocyanine salt are added to the matrix to prepare a topical ointment or a topical gel formulation.
[0007] Preferably, the skin ointment or skin gel preparation contains 0.5%-1% by mass of phycocyanin and / or phycocyanin salt.
[0008] Preferably, the ointment base of the topical skin ointment formulation is selected from one or more of beeswax, paraffin, petrolatum, liquid paraffin, lanolin, silicone, stearic acid, dimethyl silicone oil, and isooctyl palmitate.
[0009] Preferably, the base of the topical skin gel formulation is selected from carbomer or sodium alginate.
[0010] In summary, compared with the prior art, the above-described technical solutions conceived by this invention mainly possess the following technical advantages:
[0011] (1) Compared with oral SSRI antidepressants, the anxiolytic effect of the present invention is faster. Clinically, the onset time of oral SSRIs is more than 3 weeks, while the onset time in this experiment is 1 hour.
[0012] (2) Compared with benzodiazepines, the present invention has good safety, no addictive properties, and good tolerability. Clinically, oral benzodiazepines have a certain degree of addictiveness, while this drug is an edible amino acid substance and is for external use, so it will not cause addiction.
[0013] (3) This invention does not cause gastrointestinal irritation.
[0014] (4) The production process of this invention is simple, easy to transport and carry, and convenient to use. Detailed Implementation
[0015] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention. Furthermore, the technical features involved in the various embodiments of this invention described below can be combined with each other as long as they do not conflict with each other.
[0016] Overactivity in the anterior cingulate cortex may be an important biological mechanism contributing to anxiety disorders. Our team has conducted extensive basic research in recent years, discovering that the neural circuit mechanisms mediating cold perception play a crucial role in the regulation of anxiety behavior. A brief, single exposure to cold can activate the excitatory projection of oxytocin neurons from the preoptic nucleus to the paraventricular nucleus in the hypothalamus, prompting oxytocin release and its action on inhibitory interneurons in the anterior cingulate cortex, thereby inhibiting anterior cingulate cortex activity and producing an anti-anxiety effect. The alginate-type glutamate receptor GluK2, a cold receptor distributed in nerve endings of peripheral tissues such as the skin, is a key target mediating the anti-anxiety effect of cold perception. Topical application of erythrinae and / or erythrinae salts to the skin can activate GluK2 receptors and produce anti-anxiety behavioral effects.
[0017] The preparation process of the topical formulation of the present invention includes: melting the matrix components such as beeswax, paraffin, petrolatum, etc. in a water bath to form solution A, cooling it to 45℃-60℃, weighing 0.5%-1% of phycocyanin and adding it to solution A, mixing it evenly, dispensing it and cooling it to obtain an ointment formulation; or weighing carbomer or phycocyanin, adding 25-50 times its mass of ultrapure water and stirring thoroughly to prepare a gel matrix, weighing phycocyanin and adding it to ultrapure water to prepare a 5% phycocyanin solution (aqueous phase), adding the aqueous phase to the gel matrix at a mass ratio of 1:5 to 1:10 to obtain a gel formulation.
[0018] Example 1
[0019] Prescription composition: 0.01g erythrocyanine, 0.3g beeswax, 0.3g paraffin, 1.4g petrolatum.
[0020] First, weigh out 0.3g of beeswax, 0.3g of paraffin, and 1.4g of petrolatum, place them in a container, heat to 110℃ to melt and remove moisture, filter while hot, cool to 65℃~70℃, add 0.01g of algaeine and stir until completely dissolved, then bottle at 45℃~60℃ to obtain the ointment preparation.
[0021] Example 2
[0022] Prescription composition: 0.01g of erythrine and 2.5g of sodium alginate.
[0023] First, weigh 0.01 g of erythrine and dissolve it in 20 mL of sterile ultrapure water to obtain solvent A. Weigh 2.5 g of sodium alginate and add it to 80 mL of sterile ultrapure water, stirring overnight to allow it to swell fully, thus obtaining a gel matrix. Add solvent A to the gel matrix to obtain the gel formulation.
[0024] Example 3: Investigating the anxiolytic effect of the topical formulation described in this invention.
[0025] Using the drug prepared according to the method of Example 1, an empty ointment formulation with the same components (beeswax, paraffin, petrolatum) was selected as a control group. The experimental animals were 31 eight-week-old C57BL / 6J mice, weighing 20±3g, purchased from Hunan Silek Jingda Experimental Animal Company. They were randomly divided into a solvent group and a erythrine formulation group. All hair on the back of the mice from the neck to the tail was shaved, and either the control formulation or the erythrine formulation was applied to the exposed skin. Open field and elevated cross maze tests were performed 1 hour later. The results are shown in Tables 1 and 2.
[0026] Table 1. Effects of topical erythrine preparations on open field tests in mice.
[0027]
[0028] Table 2. Effects of topical erythrine preparations on the elevated cross maze test in mice.
[0029]
[0030] The T-test was used to determine the differences between the control group and the erythrocyanine preparation group. The results showed that, compared with the control group, the time for mice in the erythrocyanine preparation group to enter the open arms of the elevated cruciate maze was significantly prolonged (p<0.01). Topical application of 5‰ erythrocyanine preparation also significantly increased the number of times mice entered the open arms (p<0.05) and the distance they traveled in the open arms (p<0.01).
[0031] Compared with the control group, the topical application of erythrocyanine increased the time mice spent in the central area of the open field (p<0.05), but there was no significant difference in the total distance of movement between the two groups, indicating that the topical application of erythrocyanine did not affect the movement ability of the mice.
[0032] The above results indicate that the topical formulation of the present invention can produce an anxiolytic-like effect.
[0033] Those skilled in the art will readily understand that the above description is merely 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 within the scope of protection of the present invention.
Claims
1. Use of kainic acid and / or a kainate salt for the preparation of an anxiolytic medicament, characterized in that, The kainic acid and / or kainate salt is used to produce an anti-anxiety effect by activating the cold receptor GluK2 of peripheral tissue nerve endings and downstream cold sensation perception center, thereby producing an anti-anxiety effect; The kainic acid and / or kainate salt is added to a base to make a skin external use ointment preparation or a skin external use gel preparation; The mass content of the kainic acid and / or kainate salt in the skin external use ointment preparation or the skin external use gel preparation is 0.5% - 1%.
2. Use according to claim 1, wherein The ointment base of the skin external use ointment preparation is selected from one or more of beeswax, paraffin wax, vaseline, wool wax, silicone, stearic acid, dimethyl silicone oil, isooctyl palmitate.
3. The use according to claim 1, wherein the compound is ###0002### The base of the skin external use gel preparation is selected from carbomer or sodium alginate.