Compatibility of astragalus and golden needle and application thereof

Abstract

This invention relates to a combination of Astragalus membranaceus and daylily buds, which, when used together, exhibit significant sleep-promoting and antidepressant effects, superior to the effects of daylily buds used alone. The method includes the following steps: drying Astragalus membranaceus and daylily buds are separately powdered and passed through a 50-mesh sieve; an appropriate amount of daylily bud powder is weighed and added to 8 times the volume of 75% ethanol solution, and ultrasonically extracted at 60°C for 1-5 hours; an appropriate amount of Astragalus membranaceus powder is weighed and added to 15 times the volume of 75% ethanol solution, and ultrasonically extracted at 50°C for 40 minutes. The combination of daylily buds and Astragalus membranaceus provided by this invention shows significant sleep-promoting, antidepressant, and anti-anxiety effects. Since both Astragalus membranaceus and daylily buds are medicinal and edible substances, this combination demonstrates good safety and tolerability during long-term use. It does not produce addictive properties, avoiding the dependence problems that may arise from traditional sedative-hypnotic drugs; it does not produce withdrawal reactions, and users do not experience significant discomfort or rebound after discontinuation. Therefore, the combination of daylily buds and Astragalus membranaceus is not only effective in short-term use but also suitable for long-term use, helping to improve patients' quality of life and mental health.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceuticals, specifically relating to a combination of Astragalus membranaceus and daylily buds, and the sleep-promoting and antidepressant effects produced by the synergistic effect of the two drugs compared to the use of a single drug. Background Technology

[0002] According to a WHO survey, approximately 27% of the global population suffers from sleep disorders, making it a significant global health concern. Persistent sleep disorders can lead to various related diseases such as chronic fatigue, memory loss, weakened immunity, cardiovascular damage, and metabolic disorders. In severe cases, it can even lead to suicide. Therefore, improving sleep plays a crucial role in managing sub-health conditions, reducing the incidence of related infectious diseases, and improving people's quality of life. Sleep disorders and mental illnesses have a close interactive relationship. Sleep disorders are often comorbid with other mental illnesses, serving as a significant risk factor and common clinical symptom. The most common comorbid mental illnesses for insomnia are anxiety and depression. Similarly, mental disorders such as depressive disorders and anxiety disorders can also disrupt sleep, causing or exacerbating sleep disturbances. Depression or depressive symptoms may be the greatest risk factor for insomnia.

[0003] Daylily has a good therapeutic effect on depression. Studies by Du et al. detected flavonoids in daylily, including rutin, hesperidin, and quercetin, which have significant antidepressant effects. Li et al. also confirmed that hesperidin in daylily has an antidepressant effect on mice. Experiments by Lin et al. confirmed that the main components in daylily that inhibit depression include anthraquinones and vanillic acid compounds. Experiments by Zhai Junle et al. verified that flavonoids are important components in daylily that produce antidepressant activity, showing significant therapeutic effects on depression in mice. In clinical trials using daylily to treat hepatitis, it was unexpectedly found to have good sedative-hypnotic effects with little dependence or side effects. Lu Lanfang administered daylily extract to mice to verify its sedative effect, and the results showed that the extract indeed had a significant sedative effect on mice.

[0004] The *Huangdi Neijing* (Yellow Emperor's Inner Classic), written over 2000 years ago, already recorded sleep disorders such as "inability to close the eyes," "inability to sleep," and "inability to lie down." Traditional Chinese medicine believes that sleep disorders are mostly caused by internal factors such as emotional distress, diet, or deficiency of qi and blood. Sleep disorders easily lead to disharmony of qi and blood in the heart, liver, gallbladder, spleen, stomach, and kidneys, as well as imbalance of yin and yang. Depression is often caused by abnormal circulation of qi, blood, and body fluids, affecting the ascending, descending, entering, and exiting of qi, involving the functions of organs such as the heart, lungs, liver, spleen, and kidneys.

[0005] In view of this, the present invention is proposed. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to overcome the shortcomings of the prior art and provide a combination and application of Astragalus membranaceus and daylily, thereby solving the problems mentioned in the background art.

[0007] To solve the above-mentioned technical problems, the basic concept of the technical solution adopted by the present invention is as follows: A combination of Astragalus membranaceus and daylily buds, used to prepare a compound of Astragalus membranaceus and daylily buds, the preparation method comprising the following steps: Step (1): Prepare Astragalus membranaceus and daylily buds, and dry them in an oven. Astragalus membranaceus has the effects of tonifying qi and strengthening the exterior, promoting diuresis and reducing swelling, promoting pus drainage and tissue regeneration, and is often used in compound prescriptions to treat depression in clinical practice. Therefore, this invention combines daylily buds with Astragalus membranaceus, hoping that the two drugs will produce superior sleep-promoting and antidepressant effects through synergistic effects.

[0008] Step (2): Grind the dried Astragalus membranaceus and daylily into powder and sieve them to obtain daylily powder and Astragalus membranaceus powder respectively; Step (3): Weigh out daylily powder and astragalus powder, add the astragalus powder and daylily powder to 75% ethanol solution respectively, and perform ultrasonic extraction to obtain daylily concentrate and astragalus concentrate. Step (4): Vacuum filter the daylily concentrate and the astragalus concentrate respectively. After vacuum filtration, reduce the pressure to concentrate and remove the ethanol to obtain daylily concentrate and astragalus concentrate. Step (5): Mix the concentrated daylily extract and the concentrated astragalus extract to obtain the astragalus and daylily combination.

[0009] Optionally, 1-3 mL of daylily concentrate can be obtained from 2 g of daylily extract and concentration, and 1-3 mL of astragalus concentrate can be obtained from 10 g of astragalus extract and concentration.

[0010] Optionally, in step (1), the drying temperature of the oven is 30℃-80℃ and the drying time is 1-5h.

[0011] Optionally, the diameter of the sieve holes in step (2) is 30-50 mesh.

[0012] Optionally, in step (3), the daylily powder is extracted at 60℃-80℃ for 30 min during the ultrasonic extraction process, and the astragalus powder is extracted at 10℃-50℃ for 10 min-40 min.

[0013] Optionally, in step (3), the mass ratio of daylily powder to 75% ethanol solution is 1:8, and the mass ratio of astragalus powder to 75% ethanol solution is 1:15.

[0014] Optionally, the daylily concentrate and astragalus concentrate from step (4) are filtered through a vacuum filter to obtain filtrate, removing impurities and suspended particles.

[0015] Optionally, in step (5), the mass ratio of Astragalus membranaceus concentrate to Daylily concentrate is (1-4):(1-4).

[0016] A composition prepared by combining Astragalus membranaceus and Astragalus membranaceus as described above is used to prepare antidepressant drugs and sleep-promoting drugs. When Astragalus membranaceus is used to promote sleep, the mass ratio of Astragalus membranaceus concentrate to Astragalus membranaceus concentrate is 1:1, that is, 1 mL of the extracted Astragalus membranaceus concentrate is mixed with 1 mL of Astragalus membranaceus concentrate. When using daylily and astragalus in antidepressant medications, the mass ratio of daylily concentrate to astragalus concentrate is 2:1, that is, 2 mL of extracted daylily concentrate is mixed with 1 mL of extracted astragalus concentrate.

[0017] By adopting the above technical solution, the present invention has the following beneficial effects compared with the prior art. Of course, any product implementing the present invention does not necessarily need to achieve all of the following advantages at the same time: The combination of daylily and astragalus provided by this invention exhibits significant sleep-promoting, antidepressant, and anti-anxiety effects. This composition demonstrates good safety and tolerability during long-term use. It is non-addictive, avoiding the dependence problems that may arise from traditional sedative-hypnotic drugs; it does not cause withdrawal reactions, and users do not experience significant discomfort or rebound effects after discontinuing use. Therefore, the combination of daylily and astragalus is not only effective in the short term but also suitable for long-term use, helping to improve patients' quality of life and mental health.

[0018] The specific embodiments of the present invention will be described in further detail below. Detailed Implementation

[0019] This invention discloses a combination of Astragalus membranaceus and daylily buds for preparing a compound composition of Astragalus membranaceus and daylily buds. The preparation method includes the following steps: Step (1): Prepare astragalus and daylily, and put them into an oven to dry; Step (2): Grind the dried Astragalus membranaceus and daylily into powder and sieve them to obtain daylily powder and Astragalus membranaceus powder respectively; Step (3): Weigh out daylily powder and astragalus powder, add the astragalus powder and daylily powder to 75% ethanol solution respectively, and perform ultrasonic extraction to obtain daylily concentrate and astragalus concentrate. Step (4): Vacuum filter the daylily concentrate and the astragalus concentrate respectively. After vacuum filtration, reduce the pressure to concentrate and remove the ethanol to obtain daylily concentrate and astragalus concentrate. Step (5): Mix the concentrated daylily extract and the concentrated astragalus extract to obtain the astragalus and daylily combination.

[0020] In this embodiment, 1 mL of daylily concentrate can be obtained after extracting and concentrating 2 g of daylily, and 2 mL of astragalus concentrate can be obtained after extracting and concentrating 10 g of astragalus.

[0021] In this embodiment, the drying temperature of the oven in step (1) is 30℃-80℃, and the drying time is 1-5h.

[0022] In this embodiment, the diameter of the sieve holes in step (2) is 30-50 mesh.

[0023] In this embodiment, during the ultrasonic extraction process in step (3), daylily powder is extracted at 60℃-80℃ for 30 minutes, and astragalus powder is extracted at 10℃-50℃ for 10-40 minutes.

[0024] In this embodiment, the mass ratio of daylily powder to 75% ethanol solution in step (3) is 1:8, and the mass ratio of astragalus powder to 75% ethanol solution is 1:15.

[0025] In this embodiment, the daylily concentrate and astragalus concentrate from step (4) are filtered through a vacuum filter to obtain filtrate, thereby removing impurities and suspended particles.

[0026] In this embodiment, the mass ratio of Astragalus membranaceus concentrate to Daylily concentrate in step (5) is (1-4):(1-4).

[0027] A composition prepared by combining Astragalus membranaceus and Astragalus membranaceus as described above is used to prepare antidepressant drugs and sleep-promoting drugs. When Astragalus membranaceus is used to promote sleep, the mass ratio of Astragalus membranaceus concentrate to Astragalus membranaceus concentrate is 1:1, that is, 1 mL of the extracted Astragalus membranaceus concentrate is mixed with 1 mL of Astragalus membranaceus concentrate. When using daylily and astragalus in antidepressant medications, the mass ratio of daylily concentrate to astragalus concentrate is 2:1, that is, 2 mL of extracted daylily concentrate is mixed with 1 mL of extracted astragalus concentrate.

[0028] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0029] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0030] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be obvious to those skilled in the art. This specification and embodiments are merely exemplary.

[0031] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0032] Example 1: A combination of Astragalus membranaceus and daylily buds is provided for preparing a compound of Astragalus membranaceus and daylily buds. The preparation method includes the following steps: Step (1): Prepare astragalus and daylily, and dry them in an oven at 60℃ for 3 hours; Step (2): Grind the dried Astragalus membranaceus and daylily buds into powder and pass them through a 50-mesh sieve to obtain daylily bud powder and Astragalus membranaceus powder, respectively; Step (3): Weigh out daylily powder and astragalus powder, add 15 times and 8 times the amount of 75% ethanol solution to the astragalus powder and daylily powder respectively, and perform ultrasonic extraction to obtain daylily concentrate and astragalus concentrate. The ultrasonic conditions are: daylily is ultrasonically extracted at 60℃ for 30 min, and astragalus is ultrasonically extracted at 50℃ for 40 min. Step (4): Vacuum filter the daylily concentrate and the astragalus concentrate respectively. After vacuum filtration, reduce the pressure and concentrate to remove ethanol to obtain daylily concentrate and astragalus concentrate. Each 2g of daylily extract is concentrated to 1mL and each 5g of astragalus extract is concentrated to 1mL. Step (5): Mix the concentrated daylily extract and the concentrated astragalus extract at a mass ratio of (1:1) to obtain the astragalus and daylily compatibility composition.

[0033] Example 2: A combination of Astragalus membranaceus and daylily buds is provided for preparing a compound of Astragalus membranaceus and daylily buds. The preparation method includes the following steps: Step (1): Prepare astragalus and daylily, and dry them in an oven at 60℃ for 3 hours; Step (2): Grind the dried Astragalus membranaceus and daylily buds into powder and pass them through a 50-mesh sieve to obtain daylily bud powder and Astragalus membranaceus powder, respectively; Step (3): Weigh out daylily powder and astragalus powder, add 15 times and 8 times the amount of 75% ethanol solution to the astragalus powder and daylily powder respectively, and perform ultrasonic extraction to obtain daylily concentrate and astragalus concentrate. The ultrasonic conditions are: daylily is ultrasonically extracted at 60℃ for 30 min, and astragalus is ultrasonically extracted at 50℃ for 40 min. Step (4): Vacuum filter the daylily concentrate and the astragalus concentrate respectively. After vacuum filtration, reduce the pressure and concentrate to remove ethanol to obtain daylily concentrate and astragalus concentrate. Each 4g of daylily extract is concentrated to 2mL and each 5g of astragalus extract is concentrated to 1mL. Step (5): Mix the concentrated daylily extract and the concentrated astragalus extract at a mass ratio of (2:1) to obtain the astragalus and daylily compatibility composition.

[0034] Experiment 1: Mouse grouping: 48 mice were divided into two groups, one to examine the antidepressant effect and the other to examine the sleep-promoting effect. Each group was further divided into three subgroups: blank group, daylily group, and daylily and astragalus combination group (hereinafter referred to as combination group), with 8 mice in each group. They were administered the drugs by gavage for 21 days.

[0035] Dosage: The oral dose for mice was 0.1-0.2 mL / 10g per administration. For example, in a 40g mouse, the daylily group in the sleep-promoting group received 0.4 mL once daily; the combination group received 0.4 mL twice daily. In the antidepressant group, the daylily group received 0.4 mL twice daily; the combination group received 0.6 mL twice daily.

[0036] Experiment Example 2: Open Field Experiment (OFT) Mice were placed in a box measuring 40cm x 40cm x 20cm, with the bottom divided into 25 square areas. The recording lasted 6 minutes. Each uprighting response was defined as the mouse standing on its hind legs. The total number of uprighting responses during the experiment was recorded. The number of uprighting responses reflects the mouse's exploratory behavior and curiosity about the new environment. Mice exhibiting depressive behavior showed a decrease in the number of uprighting responses.

[0037] Suspended Tail Test (TST) Secure the mouse's tail to the rear third with tape and suspend it 5 cm above the table for 6 minutes. Calculate the immobility time (stop struggling, body in a vertical upside-down position, still) of the mouse in the last 4 minutes. The longer the immobility time in the tail suspension test, the more severe the depression.

[0038] Forced swimming test (FST) Pour 10 cm of purified water into a glass bottle (15 cm in diameter and 20 cm in height) and keep the water temperature at (24 ± 2) °C. Place the mice that have been given the drug in the glass bottle and force them to swim for 6 minutes. Calculate the resting time of the mice in the last 4 minutes.

[0039] (The person stops struggling in the water and floats, with only slight limb movements to keep their head afloat.) The longer they remain still, the more severe their depression.

[0040] Experimental results Number of times mice stood upright in open field experiment Table 1 shows that the number of times mice stood upright increased in all treatment groups compared to the control group. Specifically, there was no significant difference in the number of upright movements between the daylily group and the control group (P > 0.05), while there was a significant difference in the number of upright movements between the paired groups and the control group (P < 0.05). A higher number of upright movements indicates stronger exploratory behavior and curiosity about the new environment, and a lower level of depression in the mice. The table shows that the paired groups had the highest number of upright movements and the lowest level of depression.

[0041] Table 1. Results of the number of times mice stood upright in the open field experiment (X±S) Blank group 8 31.67±9.6 Daylily Group 8 42±6.16* 0.078 Matching group 8 46.67±9.69** 0.015 Results of the tail suspension experiment Table 2 shows that, compared with the blank group, the immobility time of mice in both treatment groups was reduced during tail suspension, but P > 0.05, indicating no significant difference. A longer immobility time in the tail suspension test indicates a more severe degree of depression. The table shows that the combined treatment group had the shortest immobility time, with a slightly better effect than the daylily group, and the mildest degree of depression.

[0042] Table 2 Results of mouse tail suspension test (X±S) Blank group 8 64±17.64 Daylily Group 8 46.33±14.15* 0.092 Matching group 8 45±14.55* 0.072 Results of forced swimming experiment Table 3 shows that, compared with the control group, the immobility time of mice in the drug-treated groups was significantly reduced during forced swimming. Specifically, the immobility time in the daylily group was significantly different from that in the control group (P < 0.05), while the immobility time in the paired groups was extremely significantly different from that in the control group (P < 0.01). A longer immobility time in the forced swimming experiment indicates a more severe degree of depression; the table shows that the paired groups had the shortest immobility time and the mildest degree of depression.

[0043] Table 3. Results of the forced swimming test in mice (X±S) Blank group 8 96±9.71 Daylily Group 8 60.58±20.72* 0.027 Matching group 8 54.43±16.7** 0.007 As shown in Experiment 2, the results of the combined group mice in the open field test, tail coiling test, and forced swimming test were all better than those of the group given daylily alone. Therefore, it is believed that the combination of Astragalus membranaceus and daylily has a synergistic effect, and the antidepressant effect is better than that of daylily alone.

[0044] Experiment to prolong sodium pentobarbital sleep time Before conducting the formal experiment, a preliminary experiment was performed to determine the sodium pentobarbital dose (21 mg / kg BW) that would induce 100% sleep in the animals without causing excessively long sleep duration. This dose was used in the formal experiment. Ten minutes after the last administration, each group of animals was intraperitoneally injected with a sodium pentobarbital aqueous solution at a dose of 0.1 mL / 10 g. The time it took for the mice to fall asleep (from the disappearance to the recovery of the righting reflex) was recorded as an indicator. The experiment observed whether the test sample could prolong the sleep duration caused by sodium pentobarbital. The difference in sleep duration prolongation between the experimental group and the control group was compared. A significant increase in sleep duration was considered a positive experimental result.

[0045] Sodium pentobarbital sleep latency test Before conducting the formal experiment, a preliminary experiment was performed to determine the optimal dose of sodium pentobarbital (21 mg / kg BW) that would induce 100% sleep in the animals without causing excessively long sleep duration. This dose was used in the formal experiment. Ten minutes after the last administration, each group of animals was intraperitoneally injected with a sodium pentobarbital aqueous solution at a volume of 10 mL / kg. The time to sleep onset (the time from intraperitoneal injection to the disappearance of the righting reflex) was recorded as an indicator to observe the effect of the test sample on the sleep latency of sodium pentobarbital. The difference in sleep latency between the experimental group and the control group was compared. A significant shortening of sleep latency was considered a positive experimental result.

[0046] Experimental results Results of prolonging sodium pentobarbital sleep duration Table 4 shows that, compared with the control group, the sleep time of mice in both treatment groups was significantly increased. P < 0.01, indicating that there was a highly significant difference in sleep duration between the daylily group and the combination group compared with the control group. However, the combination group had the longest sleep time and the best sleep-aiding effect.

[0047] Table 4. Results of the experiment on prolonging sleep time with sodium pentobarbital (X±S) Blank group 8 133.33±25.29 Daylily Group 8 169.69±14.36** 0.006 Matching group 8 189.17±11.16** 0.000 Results of shortening the sleep latency of sodium pentobarbital Table 5 shows that, compared with the control group, the sleep latency of mice in the treatment group was significantly reduced. P < 0.01, indicating that there was a highly significant difference in sleep latency between the daylily group and the combination group compared with the control group. The shorter the sleep latency, the faster the sleep onset. The daylily group had the shortest sleep latency, but the difference between it and the combination group was less than 1 minute, and the difference was not significant.

[0048] Table 5. Experimental results on shortening the sleep latency of sodium pentobarbital (X±S) Blank group 8 47±3.56 Daylily Group 8 24.57±1.7** 0.000 Matching group 8 25.29±6.29** 0.002 As shown in Experiment 3, the sleep duration and sleep latency of mice in both treatment groups were significantly different from those in the control group. The sleep duration of mice in the combination group was about 20 minutes longer than that of mice in the daylily group, and the sleep latency was about 1 minute shorter. Therefore, it is believed that the combination of Astragalus membranaceus and daylily buds has a synergistic effect, and the sleep-promoting effect is better than that of daylily buds alone.

[0049] The above experimental results show that the combination of daylily and astragalus provided by the present invention exhibits good antidepressant and sleep-promoting effects.

[0050] This invention is not limited to the embodiments described above. Anyone should understand that structural changes made under the guidance of this invention, and any technical solutions that are the same as or similar to this invention, fall within the protection scope of this invention. Technical aspects, shapes, and structures not described in detail in this invention are all publicly known technologies.

Claims

1. A sleep-promoting drug, characterized in that, The drug is prepared from Astragalus membranaceus and daylily, and the preparation method of the drug includes the following steps: Step (1): Prepare astragalus and daylily, and put them into an oven to dry. The oven temperature is 30℃-80℃ and the drying time is 1-5 hours. Step (2): Grind the dried Astragalus membranaceus and daylily into powder and sieve them to obtain daylily powder and Astragalus membranaceus powder respectively; Step (3): Weigh out daylily powder and astragalus powder, add the astragalus powder and daylily powder to 75% ethanol solution respectively, and perform ultrasonic extraction to obtain daylily extract and astragalus extract respectively; during ultrasonic extraction, daylily powder is extracted at 60℃-80℃ for 30 min, and astragalus powder is extracted at 10℃-50℃ for 10 min-40 min; the mass ratio of daylily powder to 75% ethanol solution is 1:8, and the mass ratio of astragalus powder to 75% ethanol solution is 1:15; Step (4): Vacuum filter the daylily extract and the astragalus extract respectively. After vacuum filtration, concentrate under reduced pressure to remove ethanol and obtain daylily concentrate and astragalus concentrate. 1-3 mL of daylily concentrate can be obtained from 2 g of daylily extract and 1-3 mL of astragalus concentrate can be obtained from 10 g of astragalus extract. Step (5): Mix 1 mL of daylily concentrate and 1 mL of astragalus concentrate to obtain a sleep-promoting drug.

2. The sleep-promoting drug according to claim 1, characterized in that, In step (2), the diameter of the sieve holes during the sieving process is 30-50 mesh.

3. The sleep-promoting drug according to claim 1, characterized in that, The daylily concentrate and astragalus concentrate from step (4) are filtered through a vacuum filter to obtain filtrate, removing impurities and suspended particles.