A composition having a sedative and tranquilizing effect, and a preparation method and use thereof

Abstract

The present application provides a composition with tranquilizing effect, belonging to the field of medicines or health foods. It is prepared from the following raw materials in the weight ratio: buckwheat pollen 4.8-7.2 parts, eucommia male flower 4.8-7.2 parts. The present application also provides a preparation method and use of the composition. The composition of the present application is a combination of food and medicine, buckwheat pollen and eucommia male flower have been used as health foods in daily life, and medlar is also a commonly used health food as a medicine and food. The present application has both efficacy and safety, ensures the efficacy while retaining the safety as food, and widens the application range of the combination.

Description

Technical Field

[0001] This invention relates to a composition with sedative and tranquilizing effects, its preparation method, and its uses, belonging to the field of pharmaceuticals or health foods. Background Technology

[0002] In recent years, the incidence of insomnia has been increasing. Long-term insomnia can seriously affect an individual's work and life, increase the risk of physical and mental illnesses, and create a significant economic and social burden. Sedative-hypnotic drugs are a commonly used treatment for most insomnia patients, mainly including benzodiazepine receptor agonists, melatonin receptor agonists, orexin receptor antagonists, and antidepressants that regulate sleep. However, there is currently a phenomenon of non-medical use and abuse of sedative-hypnotic drugs, primarily benzodiazepine receptor agonists. Abuse of these drugs can lead to psychological and physical dependence, cognitive impairment, depression, anxiety, increased risk of falls, and increased risk of death. Therefore, domestic and international drug regulatory authorities have successively introduced relevant policies to strengthen supervision. (Zheng Junwei, Rational Use and Abuse of Sedative-Hypnotic Drugs, Journal of Sichuan University (Medical Edition), doi:10.12182 / 20230260302).

[0003] Buckwheat pollen has a regulatory effect on the nervous system, promoting sleep and improving physical fitness. Substances in buckwheat pollen, such as pollen acids and pollen alcohols, can relieve nervous tension, thus helping to improve sleep quality.

[0004] Eucommia ulmoides is a dioecious tree, with male and female flowers being the flowers of the male Eucommia ulmoides tree. Li Xin et al., *Sedative and Tranquilizing Effects of Water-Soluble Alkaloids from Eucommia ulmoides Male Flowers*, *Food Science*, 2011, Vol. 32, No. 11, disclosed that water-soluble alkaloids from Eucommia ulmoides male flowers have good sedative and tranquilizing effects. The main effects of Eucommia ulmoides male flowers are lowering blood sugar, promoting bowel movements, and calming the nerves. However, there are certain contraindications; it should be avoided by people with heat syndromes or yin deficiency with excessive fire, as it may worsen their condition. Furthermore, the mechanism of action of Eucommia ulmoides male flowers in sedation and tranquilization is not yet clear.

[0005] There are currently no reports of combining Eucommia ulmoides male flowers with buckwheat pollen. Summary of the Invention

[0006] This invention provides a composition with sedative and tranquilizing effects, which is mainly prepared from Eucommia ulmoides male flowers and buckwheat pollen. This invention also provides a method for preparing the composition and its uses.

[0007] This invention provides a composition with sedative and tranquilizing effects, which is prepared from the following raw materials in the indicated weight ratios:

[0008] Buckwheat pollen 4.8-7.2 parts, Eucommia male flower 4.8-7.2 parts.

[0009] More preferably, it is prepared from raw materials in the following weight ratio:

[0010] Six parts buckwheat pollen and six parts Eucommia ulmoides male flowers.

[0011] The composition of the present invention is prepared from the following raw materials in the indicated weight ratios:

[0012] Buckwheat pollen 4.8-7.2 parts, Eucommia male flower 4.8-7.2 parts, wolfberry 4.8-7.2 parts.

[0013] More preferably, it is prepared from raw materials in the following weight ratio:

[0014] Six parts buckwheat pollen, six parts eucommia male flowers, and six parts wolfberry.

[0015] The composition of this invention uses buckwheat pollen, Eucommia ulmoides male flower, wolfberry powder and water extract as active ingredients, and adds acceptable excipients or auxiliary ingredients used in pharmaceuticals or health products to prepare commonly used formulations.

[0016] The preparation is either a liquid or a solid preparation.

[0017] The present invention also provides a method for preparing the composition having sedative and tranquilizing effects, comprising the following steps:

[0018] a. Weigh the raw materials according to their respective weight ratios;

[0019] b. After decocting with water to extract, filtering, and concentrating, add acceptable excipients or auxiliary ingredients from pharmaceuticals or health products to prepare commonly used formulations.

[0020] This invention provides the use of the described composition in the preparation of a medicament having a sedative and tranquilizing effect.

[0021] This invention provides the use of the described composition in the preparation of health foods that help improve sleep.

[0022] This invention provides the use of buckwheat pollen and Eucommia ulmoides male flowers in the preparation of a drug with sedative and tranquilizing effects.

[0023] The beneficial effects of this invention are:

[0024] This invention comprises three pure plant materials: buckwheat pollen, Eucommia ulmoides male flowers, and wolfberry. It possesses the effects of calming the mind and soothing the nerves, tonifying the spleen and kidneys, and replenishing qi and blood. Buckwheat pollen, the principal ingredient, nourishes the heart and calms the nerves, regulates qi and strengthens the spleen, and promotes blood circulation and removes blood stasis. Eucommia ulmoides male flowers, the assistant ingredient, nourish the liver and kidneys and calm the mind. Wolfberry, as an adjuvant ingredient, nourishes the liver and kidneys and benefits essence and eyesight.

[0025] In Traditional Chinese Medicine (TCM), insomnia is categorized into deficiency and excess patterns. TCM differentiates insomnia into five main types: deficiency of both heart and spleen, yin deficiency with exuberant fire, deficiency of heart and gallbladder qi, phlegm-heat disturbing the mind, and liver stagnation transforming into fire. This invention's combination is particularly suitable for insomnia caused by deficiency of both heart and spleen, deficiency of heart and gallbladder qi, and phlegm-heat disturbing the mind. For insomnia caused by deficiency of both heart and spleen and insufficient blood, buckwheat pollen nourishes the heart and strengthens the spleen; eucommia male flowers nourish the heart and calm the mind; and wolfberry replenishes blood. For insomnia caused by deficiency of heart and gallbladder qi and internal disturbance of phlegm, buckwheat pollen regulates qi and removes blood stasis; eucommia male flowers nourish the heart and calm the mind; and wolfberry replenishes qi and blood. For insomnia caused by food stagnation in the spleen and stomach and phlegm-heat disturbing the mind, buckwheat pollen regulates qi and strengthens the spleen; eucommia male flowers nourish the heart and calm the mind; and wolfberry replenishes essence and blood. The combined effects of these herbs are neither cloying nor stagnant, working together to nourish the heart and calm the mind.

[0026] This invention's composition combines food and medicinal ingredients. Buckwheat pollen and Eucommia ulmoides male flowers are already used daily as health foods, and wolfberry, as a medicinal ingredient, is also a commonly used health food. This invention's composition emphasizes both efficacy and safety, ensuring therapeutic effects while maintaining food safety, thus broadening the scope of its application. Detailed Implementation

[0027] Example 1: Preparation of the pharmaceutical tablets of the present invention

[0028] Take 9g of buckwheat pollen and 9g of Eucommia ulmoides male flowers; soak the buckwheat pollen and Eucommia ulmoides male flowers in water to obtain a concentrated extract, mix it with excipients and make it into granules, dry the granules, sizing them and then compressing them into tablets in a tablet press.

[0029] Example 2: Preparation of the pharmaceutical tablets of the present invention

[0030] 9g of buckwheat pollen, 9g of Eucommia ulmoides male flowers, and 9g of wolfberry were boiled in water to extract the concentrated extract. The extract was then mixed with excipients to form granules. The granules were dried, sized, and then compressed into tablets using a tablet press.

[0031] Example 3: Preparation of the drug capsule of the present invention

[0032] Grind 7.2g of buckwheat pollen, 7.2g of Eucommia male flowers, and 4.8g of wolfberry into powder, mix with excipients, form into granules, and fill into empty capsules.

[0033] Example 4: Preparation of the oral liquid drug of the present invention

[0034] 4.8g of buckwheat pollen, 7.2g of Eucommia ulmoides male flowers, and 7.2g of wolfberry were boiled in water to obtain a concentrated extract. Impurities were removed by alcohol precipitation, and appropriate additives were added to prepare the solution. After dispensing and sterilization, the oral liquid was obtained.

[0035] Example 5: Preparation of the drug granules of the present invention

[0036] Grind 7.2g of buckwheat pollen, 4.8g of Eucommia male flowers, and 4.8g of wolfberry into powder, mix with the auxiliary materials, and then make into granules.

[0037] Example 6: Preparation of the solid beverage of the present invention

[0038] Extract 6g of buckwheat pollen, 6g of Eucommia ulmoides male flowers, and 6g of wolfberry to obtain an extract paste. Add an appropriate amount of dextrin and other excipients and mix to obtain 10g of solid beverage.

[0039] Example 7: Preparation of the food biscuit of the present invention

[0040] Buckwheat pollen, eucommia male flowers, and goji berries are ground into powder, mixed with flour, powdered sugar, and other auxiliary ingredients to form a dough, which is then pressed into shape and baked to obtain cookies.

[0041] Specific process parameters are as follows: Buckwheat pollen, Eucommia male flowers, and wolfberries (1:1:1) are ground into fine powder, sieved, and mixed. For every 100g of the powder, 425g of low-gluten flour and 125g of water are mixed. Then, 125g of powdered sugar, 150g of butter, 7.5g of salt, and 10g of baking soda are added to form a dough. After pressing and shaping, the dough is baked to obtain the final product.

[0042] Example 8: Preparation of the bread of the present invention

[0043] Buckwheat pollen, Eucommia male flowers, and wolfberry are extracted to obtain a concentrated extract. This extract is then mixed with flour, yeast, and other auxiliary ingredients, divided into portions, proofed, and baked to obtain bread.

[0044] The following specific efficacy tests demonstrate the beneficial effects of the present invention.

[0045] Test Example 1: Pharmacodynamic Test of the Composition of the Invention

[0046] I. Experimental Materials

[0047] 1. Test drug and reagent

[0048] (1) Buckwheat pollen, batch number: R45214032, Xinzhou Wutaishan Bee Industry Co., Ltd.;

[0049] (2) Eucommia ulmoides male flowers, batch number: 202403001, Guangyuan Yiming Biotechnology Co., Ltd.;

[0050] (3) Goji berries, batch number: 2024050901, purchased from Hehuachi Medicinal Herbs Professional Market in Chengdu;

[0051] (4) Jujube Seed Tranquilizing Capsules, batch number: 220707, Tongjitang (Guizhou) Pharmaceutical Co., Ltd.;

[0052] (5) Sodium pentobarbital, batch number: 020919, Beijing Chemical Reagent Company;

[0053] (6) Physiological sodium chloride solution, batch number: L23111808, Sichuan Kelun Pharmaceutical Co., Ltd.

[0054] 2. Instruments and consumables

[0055] Table 1 Experimental Instruments

[0056] Instrument Name brand model Electronic balance Shanghai Yueping Scientific Instruments Co., Ltd. YP30002 Ultrapure water system Sichuan Youpu Ultrapure Technology Co., Ltd. UPH-I-10T constant temperature water bath Shanghai Yarong Biochemical Instrument Factory B-200 Rotary evaporator Shanghai Yarong Biochemical Instrument Factory RE52CS Circulating water vacuum pump Gongyi Yuhua Instrument Co., Ltd. SHB-III Electronic temperature-controlled heating mantle Bonsai Instruments Technology (Shanghai) Co., Ltd. DZTW type Mouse spontaneous activity tester Chengdu Taimeng Technology Co., Ltd. ZZ-6 One ten-thousandth balance Shanghai Yueping Scientific Instruments Co., Ltd. 03P516

[0057] 3. Laboratory animals

[0058] Male KM mice, SPF grade, weighing 18–20g. Provided by Chengdu Dashuo Experimental Animal Co., Ltd., Laboratory Animal Quality Certificate No.: SCXK (Sichuan) 2020-0030.

[0059] II. Experimental Methods

[0060] 1. Preparation of drug solution

[0061] 1.1 Preparation of extracts from traditional Chinese medicine formulations

[0062] The herbal formula is shown in Table 2. The herbs are decocted and extracted twice. For the first decoction, add 10 times the amount of water and decoct for 1 hour. For the second decoction, add 8 times the amount of water and decoct for 1 hour. Filter the decoction through a 200-mesh filter cloth. Concentrate the filtrate to 100ml (equivalent to 0.18g of raw herb / ml). (For adults weighing 60kg, the daily dosage is 18g).

[0063] For animal administration, use the medium dose (clinically equivalent dose).

[0064] Table 2 Grouping and Contents of Traditional Chinese Medicine Formulas

[0065] Formula group Formula content 1 6g buckwheat pollen, 6g eucommia male flowers, 6g goji berries 2 18g of buckwheat pollen 3 18g of Eucommia ulmoides male flowers 4 18g of goji berries 5 9g buckwheat pollen, 9g eucommia male flowers

[0066] 1.2 Preparation of positive control solution for jujube seed sedative capsules

[0067] Take the contents of 4 capsules (0.45g / capsule) and add 80ml of pure water to prepare a positive control solution of 0.0225g / mL. (The instructions for Zao Ren An Shen Capsules state: Adults, 5 capsules once a day, i.e., the dosage for mice is 0.45g / kg).

[0068] For animal administration, use the medium dose (clinically equivalent dose).

[0069] 2. Grouping and administration

[0070] Forty-two male KM mice that met the experimental requirements were pre-selected and randomly divided into seven groups (blank control group, formulations 1-5, and the positive control group of jujube seed sedative capsules), with six mice in each group. The blank control group was administered an equal volume of distilled water by gavage daily, while the treatment groups were administered the corresponding drug solution by gavage. The mice in each group were administered the drug by gavage for 7 consecutive days, once a day, at 9 AM, with a gavage volume of 0.4 ml / 20 g.

[0071] 3. Experimental Design

[0072] Three pharmacodynamic experiments were designed with reference to "Methodology of Pharmacological Research of Traditional Chinese Medicine (3rd Edition)" and "Methods for Functional Testing and Evaluation of Health Foods (2023 Edition)".

[0073] 3.1 Study on the sedative effect of the formulation: its influence on spontaneous activity in mice

[0074] One hour after the last administration, the mice were placed in a multifunctional spontaneous activity recorder. After acclimatization for 5 minutes, the activity and number of times each group of animals stood were recorded over 5 minutes.

[0075] 3.2 Study on the sedative effect of the formulation: Experiment on prolonging the sleep time of sodium pentobarbital

[0076] The synergistic sleep-inducing effect of the test substance and a suprathreshold dose of sodium pentobarbital (45 mg / kg, intraperitoneal injection) was observed. Sleep latency (from the injection of sodium pentobarbital to the disappearance of the righting reflex) and sleep duration were recorded. Sleep onset was defined as occurring more than 1 minute after the righting reflex disappeared, and sleep duration was defined as the time from the disappearance of the righting reflex to its recovery.

[0077] 3.3 Study on the sedative effect of the formulation: Effect on sleep time of subthreshold doses of sodium pentobarbital

[0078] The synergistic sleep-inducing effect of the test substance and a subthreshold hypnotic dose of pentobarbital sodium (25 mg / kg, intraperitoneal injection) was observed. The percentage of sleep onset, sleep latency (from the injection of pentobarbital sodium to the disappearance of the righting reflex), and sleep duration were recorded within 30 minutes. Sleep onset was defined as occurring more than 1 minute after the righting reflex disappeared, and sleep duration was defined as the time from the disappearance of the righting reflex to its recovery.

[0079] 4. Statistical methods

[0080] Statistical analysis was performed using SPSS 26.0 software. All data are expressed as mean ± standard deviation (±s). Results are presented in numerical form. P <0.05 indicates that the difference is statistically significant.

[0081] III. Experimental Results

[0082] 1. Study on the sedative effect of the formula: Results of its influence on spontaneous activity in mice.

[0083] The results of spontaneous activity in mice are shown in Table 3.

[0084] Table 3 Results of the mouse spontaneous activity experiment ( ±s, n=6)

[0085] Group Number of activities / times Number of times to stand up / times Blank control group 119.0±16.0 49.7±12.3 Jujube Seed Anshen Capsules Positive Drug Group 70.5±12.0** 27.0±13.0* Formula 1 62.7±15.1** 17.7±13.8** Formula 2 82.8±26.1* 31.2±16.2 Group 3 86.7±22.8* 44.8±12.0 Formula 4 groups 100.7±34.9 40.8±22.1 Formula 5 groups 72.3±25.6** 39.3±9.6

[0086] Note: Compared with the blank control group, * P <0.05,** P <0.01.

[0087] As shown in Table 3, compared with the blank control group, the number of activities and standing times in group 1 were significantly lower than those in the blank control group. P <0.01), the number of activity events in the positive drug group and the group 5 of the jujube seed calming capsule were significantly lower than those in the blank group ( P <0.01), the number of activities in group 2 and group 3 was lower than that in the blank group ( P <0.05), the number of standing times in the positive drug group of Zao Ren An Shen Capsules was lower than that in the blank group ( P <0.05), the difference was statistically significant.

[0088] Conclusion: The above results show that formulations 1, 2, 3 and 5 have a sedative effect, among which formulation 1 has the best sedative effect.

[0089] 2. Study on the sedative effect of the formulation: Experiment to prolong the sleep time of sodium pentobarbital

[0090] The experimental results of the effect of suprathreshold doses of sodium pentobarbital on sleep in mice are shown in Table 4.

[0091] Table 4. Effects of different drug administration methods on sleep duration at suprathreshold doses of pentobarbital sodium ( ±s, n=6)

[0092] Group Sleep latency / min Sleep time / min Blank control group 7.83±2.48 71.00±16.29 Jujube Seed Anshen Capsules Positive Drug Group 4.00±0.82* 105.83±11.68** Formula 1 2.83±0.69** 135.33±16.76** Formula 2 5.17±2.27 103.50±16.82** Formula 3 7.76±3.54 100.33±21.41** Formula 4 groups 6.33±3.40 85.83±9.58 Formula 5 groups 4.33±1.80* 102.83±20.18**

[0093] Note: Compared with the blank group, * P <0.05,** P <0.01.

[0094] As shown in Table 4, all animals in each group fell asleep. Compared with the blank control group, the sleep latency of group 1 was significantly lower than that of the blank control group. P <0.01), the sleep latency of the positive drug group and the group 5 of the jujube seed calming capsule was significantly lower than that of the blank group ( P <0.05), the sleep time of the positive drug group, formula 1 group, formula 2 group, formula 3 group, and formula 5 group of Zao Ren An Shen capsules was significantly higher than that of the blank group. P<0.01).

[0095] Conclusion: The above results show that formulations 1, 2, 3 and 5 can all prolong the sodium pentobarbital sleep time in mice and have a sedative effect. Among them, formulations 1 and 5 have outstanding effects, while formulation 1 has the best effect.

[0096] 3. Study on the sedative effect of the formulation: Effect of subthreshold doses of sodium pentobarbital on sleep duration

[0097] The experimental results of the effect of subthreshold doses of sodium pentobarbital on sleep in mice are shown in Table 5.

[0098] Table 5. Effects of different administration methods on sleep duration at subthreshold doses of pentobarbital sodium ( ±s, n=6)

[0099] Group percentage of people falling asleep Sleep latency / min Sleep time / min Blank control group 50.0% 26.33±2.49 18.67±11.15 Jujube Seed Anshen Capsules Positive Drug Group 66.7% 13.00±2.55* 57.75±8.44** Formula 1 83.3% 11.60±3.20** 57.40±10.13** Formula 2 66.7% 22.25±5.07 25.25±6.83 Formula 3 50.0% 15.33±2.49 33.00±5.66 Formula 4 groups 50.0% 25.33±3.09 15.67±9.18 Formula 5 groups 66.7% 14.25±2.86* 34.5±7.50

[0100] Note: Compared with the blank group, * P <0.05,** P <0.01.

[0101] As shown in Table 5, the number of animals falling asleep in the positive drug group, formulation 1, formulation 2, and formulation 5 of the jujube seed calming capsule were all higher than that in the control group. Compared with the control group, the sleep latency of formulation 1 was significantly lower than that of the control group. P <0.01), the sleep latency of the positive drug group and the group 5 of the jujube seed calming capsule was significantly lower than that of the blank group ( P <0.05), the sleep time in the positive drug group and the first group of the jujube seed calming capsules was significantly higher than that in the blank group ( P <0.01).

[0102] Conclusion: The above results indicate that both formulation 1 and formulation 5 can reduce the sleep latency of mice and prolong the sodium pentobarbital sleep time, thus having a sedative effect. Formulation 1 showed the best effect.

[0103] IV. Experimental Conclusions

[0104] Insomnia refers to a long-term state of poor sleep quality and is the most common sleep disorder in clinical practice. Severe insomnia can even affect normal work during the day. Symptoms of insomnia include difficulty falling asleep, shallow sleep, easy awakening or early awakening, vivid dreams, and fatigue after waking. Zao Ren An Shen Capsules are used to treat insomnia, dizziness, and forgetfulness by nourishing the heart and calming the mind. This experiment mainly involved administering Zao Ren An Shen Capsules as a positive control and five different formulations of traditional Chinese medicine to mice via gavage, comparing them with a blank control group. The effects of different formulations on spontaneous activity and sleep in mice were then investigated, and the optimal formulation was selected based on the experimental results. The experimental results show that Formulation 1 had the best sedative and calming effect on mice. Therefore, Formulation 1 (6g buckwheat pollen, 6g Eucommia ulmoides male flower, and 6g Lycium barbarum) was selected as a formula for use in health food or pharmaceutical development.

Claims

1. A composition having a sedative and tranquilizing effect, characterized by: It is prepared from the following raw materials with the following weight ratio: Buckwheat pollen 6 parts, Eucommia ulmoides male flower 6 parts, Chinese wolfberry 6 parts; It comprises the following steps: a. Weighing each weight ratio of raw materials; b. Adding water to decoct and extract, filtering, and adding acceptable adjuvants in pharmaceutical or health care products to prepare common preparations.

2. The composition having a sedative and tranquilizing effect according to claim 1, characterized by: It is the raw powder of buckwheat pollen, Eucommia ulmoides male flower and Chinese wolfberry, and the water extract is the active ingredient, and acceptable adjuvants in pharmaceutical or health care products are added to prepare common preparations.

3. The composition having a sedative effect according to claim 2, characterized by: The preparation is a liquid preparation or a solid preparation.

4. A process for the preparation of a composition having tranquilizing and sedative action as claimed in any one of claims 1 to 3, wherein: It comprises the following steps: a. Weighing each weight ratio of raw materials; b. Adding water to decoct and extract, filtering, and adding acceptable adjuvants in pharmaceutical or health care products to prepare common preparations.

5. Use of the composition according to any one of claims 1-3 in the preparation of a drug with the function of calming the nerves.

6. Use of the composition according to any one of claims 1-3 in the preparation of a health care food for improving sleep.