Anti-depression composition, compound preparation and application thereof

Abstract

The invention relates to the technical field of plant extraction, and particularly provides an anti-depression composition, a compound preparation and application of the anti-depression composition and the compound preparation. The anti-depression composition is prepared from the following components in parts by mass: 1 to 5 parts of ageratum conyzoides extract, 1 to 5 parts of cinnamomum burmanni extract and 5 to 10 parts of snow vanilla extract. Compared with the prior art, the anti-depression composition disclosed by the invention is good in anti-depression curative effect, low in cost, small in side effect, suitable for being taken for a long time, safe and reliable, and is mainly used for mild and moderate depression.

Description

Technical Field

[0001] The present invention relates to the technical field of plant extraction, and more specifically to an antidepressant composition, a compound preparation and applications thereof. Background Art

[0002] Depression, also known as depressive disorder, is a mental disorder with a high incidence, high clinical cure rate, but low treatment acceptance rate and high recurrence rate. Its main feature is significant and persistent low mood. Some patients may have self-harm, suicidal behavior, and may even be accompanied by psychotic symptoms such as delusions and hallucinations. Depression is mainly manifested by low mood, loss of interest, and lack of energy. There are also some early symptoms such as slow reaction, slow thinking, and memory loss, but these will vary from person to person. Depression is not contagious, but it is closely related to stressful life events, pessimistic personality traits, a history of other mental illnesses, serious chronic diseases, alcoholism, and drug abuse. Each episode of depression lasts for at least 2 weeks, and even several years for the elderly. Most cases tend to relapse, and most episodes can be relieved, while some may have residual symptoms or become chronic.

[0003] The etiology of depression is complex, and many biological, psychological and social environmental factors are involved in the pathogenesis of depression. Biological factors involve genetics, neurochemistry, neuroendocrine, and neural regeneration; the psychological susceptibility that is closely related to depression is the premorbid personality trait. Encountering stressful life events in adulthood is an important trigger for clinically significant depressive episodes.

[0004] The treatment of depression is mainly antidepressants. Currently, the first-line antidepressants in clinical practice mainly include selective serotonin reuptake inhibitors (representative drug paroxetine hydrochloride), serotonin and norepinephrine reuptake inhibitors, norepinephrine and specific serotonergic antidepressants, etc. Traditional tricyclic and tetracyclic antidepressants and monoamine oxidase inhibitors have large adverse reactions. At present, natural drugs with antidepressant effects are urgently needed. Summary of the invention

[0005] In view of this, the object of the present invention is to provide an antidepressant composition, a compound preparation and use thereof. The antidepressant composition of the present invention has good antidepressant efficacy, low cost, few side effects, is suitable for long-term use, is safe and reliable, and is mainly used for mild and moderate depression.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] An antidepressant composition comprises, by weight, 1 to 5 parts of ageratum extract, 1 to 5 parts of burmannia glutinosa extract and 5 to 10 parts of scutellaria baicalensis extract.

[0008] Ageratum conyzoides L. is an annual herbaceous plant of the genus Ageratum in the Asteraceae family. It has no obvious taproot. Its stem is thick and 4 mm in diameter at the bottom. Its stems and branches are light red, or green on the upper part and covered with white dusty short hairs. Ageratum conyzoides can clear away heat and detoxify, disperse blood stasis and stop bleeding, and reduce swelling and detoxify. It is traditionally used to treat symptoms such as heat-toxic diseases, carbuncles, sores, and blood stasis.

[0009] Cinnamomum burmanni (Nees & T.Nees) Blume, also known as Yin grass, cinnamon, earth cinnamon, false cinnamon, mountain laurel, laurel, etc., has three radicular veins, but no glandular dots in the vein axils, which distinguishes it from camphor. The bark is gray-brown to dark brown, with a cinnamon-like smell. Cinnamomum burmanni leaves can be used as a digestive herb to relieve indigestion, stomach cramps and flatulence. Cinnamomum burmanni leaves also have certain antibacterial and antifungal properties and can be used to treat skin infections and other fungal infections.

[0010] Hedyosmum orientale Merr. & Chun is a herb or shrub of the genus Hedyosmum in the family Chrysanthemiaceae. The whole plant of Hedyosmum orientale can be used as medicine. It tastes bitter and pungent, is neutral in nature, and has the effects of reducing swelling and toxins, dispersing blood stasis and relieving pain. It can be used to treat symptoms such as early stage of mastitis, sore throat, and traumatic injuries.

[0011] Preferably, the method for preparing the ageratum leaf extract comprises: mixing ageratum leaf with ethanol, extracting at 100° C. for 2 to 10 hours, filtering, concentrating and drying the filtrate to obtain the ageratum leaf extract.

[0012] Preferably, the solid-liquid ratio of the ageratum to ethanol is 1:(8-10) g / ml.

[0013] Preferably, the ageratum extract is prepared from the whole herb of ageratum.

[0014] Preferably, the method for preparing the Cinnamomum burmanii extract comprises: mixing Cinnamomum burmanii with ethanol, extracting at 100° C. for 2 to 10 hours, filtering, concentrating and drying the filtrate to obtain the Cinnamomum burmanii extract.

[0015] Preferably, the solid-liquid ratio of Cinnamomum burmanii to ethanol is 1:(8-10) g / ml.

[0016] Preferably, the Cinnamomum burmanii extract is prepared from Cinnamomum burmanii leaves.

[0017] Preferably, the method for preparing the snow hyacinth extract comprises: mixing snow hyacinth with ethanol, extracting at 100° C. for 2 to 10 hours, filtering, concentrating and drying the filtrate to obtain the snow hyacinth extract.

[0018] Preferably, the solid-liquid ratio of the snow fragrant orchid to ethanol is 1:(8-10) g / ml.

[0019] Preferably, the Herba Citri Reticulatae Extract is prepared from the whole Herba Citri Reticulatae.

[0020] Preferably, the antidepressant composition comprises, by weight, 3 parts of Ageratum cochinchinensis extract, 3 parts of Cinnamomum burmanii extract and 7 parts of Scutellaria baicalensis extract;

[0021] Alternatively, the antidepressant composition comprises, by weight, 2 parts of Ageratum cochinchinensis extract, 2 parts of Cinnamomum burmanii extract and 10 parts of Scutellaria baicalensis extract;

[0022] Alternatively, the antidepressant composition comprises, by weight, 5 parts of Ageratum cochinchinensis extract, 5 parts of Cinnamomum burmanii extract and 5 parts of Scutellaria baicalensis extract;

[0023] Alternatively, the antidepressant composition comprises, by weight, 2 parts of Ageratum cochinchinensis extract, 4 parts of Cinnamomum burmanii extract and 8 parts of Scutellaria baicalensis extract.

[0024] The present invention also provides the use of the antidepressant composition in preventing and / or treating nervous system diseases.

[0025] Preferably, the nervous system disease comprises one or more of insomnia, mood relief, sleep disturbance, headache, depression or anxiety.

[0026] The present invention also provides a compound preparation, comprising the antidepressant composition.

[0027] Preferably, the dosage form of the compound preparation includes one or more of powder, capsule, tablet, pill, granule, extract, and syrup.

[0028] Compared with the prior art, the antidepressant composition of the present invention is characterized in that, measured by mass, it includes 1 to 5 parts of ageratum extract, 1 to 5 parts of burmanna extract and 5 to 10 parts of scutellaria extract; the present invention creatively combines ageratum extract, burmanna extract and scutellaria extract, and the obtained composition has good antidepressant efficacy, low cost, small side effects, is suitable for long-term use, is safe and reliable, and is mainly used for mild and moderate depression. DETAILED DESCRIPTION

[0029] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0030] In order to further illustrate the present invention, the following examples are used to explain it in detail. The raw materials used in the following examples and comparative examples of the present invention are all commercially available products.

[0031] The method for preparing the Ageratum cochinchinensis extract in the embodiment of the present invention comprises the following steps:

[0032] The whole herb of Ageratum is crushed and passed through a 10-mesh sieve, and 8 times the amount of ethanol as that of Ageratum is added, heated to boiling, extracted for 2 hours, filtered, the filtrate and the residue are separated, the residue is extracted twice again, the filtrates after three extractions are combined, concentrated until there is no alcohol taste, and dried to obtain the Ageratum extract.

[0033] The method for preparing the Cinnamomum burmanii extract in the embodiment of the present invention comprises the following steps:

[0034] Crush the leaves of Cinnamomum burmanii and pass them through a 10-mesh sieve. Add 8 times the amount of ethanol as that of Cinnamomum burmanii, heat to boiling, extract for 2 hours, filter, separate the filtrate and the residue, repeat the extraction of the residue for 2 more times, combine the filtrates after 3 extractions, concentrate until there is no alcohol taste, and dry to obtain the Cinnamomum burmanii extract.

[0035] The method for preparing the snow hyacinth extract in the embodiment of the present invention comprises the following steps:

[0036] Grind the whole herb of snow vanilla and pass it through a 10-mesh sieve, add 8 times the amount of ethanol as snow vanilla, heat to boiling, extract for 2 hours, filter, separate the filtrate and the residue, repeat the extraction of the residue 2 times, combine the filtrates after 3 extractions, concentrate until there is no alcohol taste, and dry to obtain the snow vanilla extract.

[0037] Example 1

[0038] The antidepressant composition of this embodiment is composed of the following components: 300 g of Ageratum cochinchinensis extract, 300 g of Cinnamomum burmanii extract, and 700 g of Scutellaria baicalensis extract.

[0039] The preparation method of the antidepressant composition of this embodiment comprises the following steps: 300 g of Ageratum cochinchinensis extract, 300 g of Cinnamomum burmanii extract and 700 g of Scutellaria baicalensis extract are mixed to obtain the antidepressant composition.

[0040] Example 2

[0041] The antidepressant composition of this embodiment is composed of the following components: 200 g of Ageratum cochinchinensis extract, 200 g of Cinnamomum burmanii extract, and 1000 g of Scutellaria baicalensis extract.

[0042] Example 3

[0043] The antidepressant composition of this embodiment is composed of the following components: 500 g of Ageratum cochinchinensis extract, 500 g of Cinnamomum burmanii extract, and 500 g of Scutellaria baicalensis extract.

[0044] Example 4

[0045] The antidepressant composition of this embodiment is composed of the following components: 200 g of Ageratum cochinchinensis extract, 400 g of Cinnamomum burmanii extract, and 800 g of Scutellaria baicalensis extract.

[0046] Comparative Example 1

[0047] The composition of this comparative example is different from that of Example 1 in that this comparative example only includes the Ageratum cochinchinensis extract and the Cinnamomum burmanii extract; the missing amount of the Herba Citri Reticulatae Extract is distributed to the corresponding components according to the ratio of the other two substances.

[0048] Comparative Example 2

[0049] The composition of this comparative example is different from that of Example 1 in that this comparative example only includes the Ageratum cochinchinensis extract and the Herba Citri Reticulatae Sinensis extract; the missing amount of the Herba Citri Reticulatae Sinensis extract is distributed to the corresponding components according to the ratio of the other two substances.

[0050] Comparative Example 3

[0051] The composition of this comparative example is different from that of Example 1 in that this comparative example only includes the snow hyacinth extract and the burmanae extract; the missing amount of the extract is distributed to the corresponding components according to the ratio of the other two substances.

[0052] Test Example 1 Toxicity Test

[0053] 40 healthy mice, weighing 25-30 g, were selected and randomly divided into 4 groups, with half males and half females in each group. The compositions of the embodiments and comparative examples were administered by gavage, with a dosage of 3 mg / g, once in the morning and once in the evening. After continuous observation for 14 days, no death or abnormal toxic reaction was observed in the mice after gavage administration, and the mice had good diet and activities, and no death was observed. After 60 days of administration, the mice in each group had no abnormal performance, were active in behavior, had a normal diet, and had an average body weight of 40 g. There were no significant differences in blood counts, biochemical indices, urine routine indices, and organ coefficients, indicating that the medication is safe within the prescription range of the present invention.

[0054] Test Example 2 Pharmacological Experiment

[0055] The sugar water preference test and the depression triad (open field test + forced swimming test + tail suspension test) were used as behavioral detection methods for screening the activity of antidepressant drugs to verify the antidepressant efficacy of the composition, providing an experimental basis for the development of traditional Chinese medicine for the treatment of depression.

[0056] 1. Animals and groups

[0057] SPF male C57BL / 6J mice, body weight 25-30g, 70 mice. Provided by Jinan Pengyue Experimental Animal Breeding Co., Ltd., license number: SCXK (Lu) 2018-0003. Randomly divided into 7 groups (n = 10), namely: blank control group, model group, positive control (paroxetine hydrochloride tablets) group, Example 1-4 group, comparative example 1-3 group, 10 mice in each group, each group was raised in a single cage. Raised in a light and temperature and humidity controlled room: temperature 21 ± 2 ° C, humidity 50 ± 10%, 12h / 12h light and dark cycle (lights on at 20:00, lights off at 8:00), all animal experimental operations are carried out in accordance with the guidelines for the welfare and use of experimental animals promulgated by NIH.

[0058] 2. Positive control drug: Paroxetine hydrochloride tablets: Zhejiang Huahai Pharmaceutical Co., Ltd., national medicine standard number H20031106, 20 mg / tablet.

[0059] 3. Modeling and drug administration

[0060] After grouping, mice other than the blank control group were modeled, and each group received various stimulations for 21 days, including: day and night reversal for 24 hours, water deprivation for 24 hours, fasting for 24 hours, tilting for 24 hours, humidity for 24 hours, restraint for 2 hours, ice water swimming for 3 minutes, hot water swimming for 3 minutes, tail clamping for 1 minute, electric shock, noise for 2 hours, shaking for 5 minutes, odor for 24 hours (different odors every week), and foreign objects for 24 hours (different foreign objects every week). Two types were randomly selected every day, and each was used twice a week. The same type of stimulation could not appear continuously, which was unpredictable. After 14 days, the stimulation ended and gavage began. The medication was administered for a total of 14 days. After the gavage treatment, the sugar water preference test, open field test, forced swimming test and tail suspension test were performed. The medication method and dosage of each group of mice are shown in Table 1 below.

[0061] Table 1

[0062] Group Drug name Dosage Gavage volume / mouse weight Blank control group Normal saline - 0.01mL / g Model Group Normal saline - 0.01mL / g Positive control group Paroxetine Hydrochloride Tablets 10 mg / kg / day 0.01mL / g Example 1 Group Example 1 Composition obtained 5 g / kg / day 0.01mL / g Example 2 Group Example 2 Composition obtained 8 g / kg / d 0.01mL / g Example 3 Group Example 3 Composition obtained 10 g / kg / day 0.01mL / g Example 4 Group Example 4 Composition obtained 15 g / kg / day 0.01mL / g Comparative Example 1 The obtained composition of comparative example 1 5 g / kg / day 0.01mL / g Comparative Example 2 Comparative Example 2 Composition obtained 5 g / kg / day 0.01mL / g Comparative Example 3 Comparative Example 3 Composition obtained 5 g / kg / day 0.01mL / g

[0063] 4. Experimental methods

[0064] 4.1 Sugar water preference experiment

[0065] Before the formal experiment, 48 hours of sugar water training was conducted. In the first 24 hours, two bottles of 1% sucrose water were placed at the water inlets at both ends of each cage. In the second 24 hours, one bottle of 1% sucrose water and one bottle of pure water were placed at the water inlets at both ends of each cage (the positions of the two water bottles were swapped at the 12th hour to avoid position preference). After 23 hours of fasting and water deprivation, each mouse was given a bottle of 1% sucrose water and pure water. The consumption of sucrose water and pure water by the mouse within 1 hour was recorded. The mouse's preference coefficient for sucrose SP (Sucrose Preference) was calculated using the following formula, and the degree of anhedonia was assessed by detecting the mouse's response to rewards.

[0066] Sugar water preference coefficient = sugar water consumption (g) / [sugar water consumption (g) + water consumption (g)] × 100%

[0067] 4.2 Mouse open field test

[0068] The experiment was conducted in an open field box with a length of 50 cm, a width of 50 cm, and a depth of 50 cm. The bottom of the open field box was divided into 9 squares, with the middle area being the central area and the remaining areas being the peripheral areas. The bottom and surrounding areas of the open field box were all white. The experiment was conducted in a quiet environment with weak red light. At the beginning, the mice were placed in the center of the open field box and their activities were observed within 6 minutes. The total movement distance of the mice in the last 4 minutes was recorded. After the experiment of each mouse, the feces was removed and the open field box was wiped with 75% ethanol to avoid residual odors interfering with subsequent experiments.

[0069] 4.3 Mouse forced swimming test

[0070] When forced to swim, all animals were placed in 5000mL of 25cm deep water at 24±1℃. After 15 minutes, they were transferred to a 30℃ dry environment for 30min (preliminary experiment). After 24 hours, the mice were placed in the organic glass cylinder again for 6min (formal experiment). During this period, the camera was used to record. After one mouse was done, the water was changed and the cylinder was cleaned. The mice showed passive floating, with only slight movements of the limbs to keep floating, and the disappearance of struggling behavior lasting for 3s was considered to be immobile. The cumulative immobility time of the mice in the forced swimming within the next 4min was calculated.

[0071] 4.4 Mouse tail suspension test

[0072] In the tail suspension experiment, the tip of the mouse's tail was suspended on the tail suspension device with medical tape at 1 / 3 of its tip. The mouse was suspended in a vertical position with its head facing the camera, about 30 cm above the ground. The immobility time of each group of mice in the tail suspension experiment was recorded by video for 6 minutes, and the immobility time of the mouse tail suspension was calculated after 4 minutes. The immobility time was judged as the mouse stopped struggling, was in an upside-down hanging state, and was motionless.

[0073] 5. Test results

[0074] Table 2

[0075]

[0076] Note: * indicates P<0.01 compared with the positive control group; ** indicates P<0.01 compared with the model group; a indicates P<0.01 compared with the Example 1 group.

[0077] From the above data, it can be seen that compared with the blank group, the sucrose preference value of the model group was significantly reduced, and the total distance of the mine experiment, the cumulative immobility time of forced swimming and the immobility time of tail suspension were significantly increased, indicating that the model was successfully established; and the sucrose preference test values ​​of the positive drug group and the embodiment group treated with oral administration were larger than those of the model group, among which the treatment effect of the embodiment 2-4 group was equivalent to that of the positive drug, or even better; the total immobility time and the immobility time of tail suspension in forced swimming were significantly shortened compared with the model group, and the embodiment 2-4 group was equivalent to the positive drug, indicating that each group of the embodiment had a therapeutic effect on depression.

[0078] The above description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. An antidepressant composition, characterized in that: Calculated by weight, the invention comprises 1 to 5 parts of ageratum extract, 1 to 5 parts of burmannia glutinosa extract and 5 to 10 parts of scutellaria baicalensis extract.

2. The antidepressant composition according to claim 1, characterized in that The preparation method of the ageratum extract comprises: mixing the ageratum with ethanol, extracting at 100° C. for 2 to 10 hours, filtering, concentrating and drying the filtrate to obtain the ageratum extract.

3. The antidepressant composition according to claim 2, characterized in that The solid-liquid ratio of the ageratum to ethanol is 1:(8-10) g / ml.

4. The antidepressant composition according to claim 1, characterized in that The preparation method of the Cinnamomum burmanii extract comprises: mixing Cinnamomum burmanii with ethanol, extracting at 100° C. for 2 to 10 hours, filtering, concentrating and drying the filtrate to obtain the Cinnamomum burmanii extract.

5. The antidepressant composition according to claim 4, characterized in that The solid-liquid ratio of the Cinnamomum burmanii to ethanol is 1:(8-10) g / ml.

6. The antidepressant composition according to claim 1, characterized in that The preparation method of the snow hyacinth extract comprises: mixing the snow hyacinth with ethanol, extracting at 100°C for 2 to 10 hours, filtering, concentrating and drying the filtrate to obtain the snow hyacinth extract.

7. The antidepressant composition according to claim 6, characterized in that The solid-liquid ratio of the snow fragrant orchid to ethanol is 1:(8-10) g / ml.

8. The antidepressant composition according to claim 1, characterized in that In parts by mass, it comprises 3 parts of Ageratum officinale extract, 3 parts of Cinnamomum burmanii extract and 7 parts of Scutellaria baicalensis extract; Alternatively, the antidepressant composition comprises, by weight, 2 parts of Ageratum cochinchinensis extract, 2 parts of Cinnamomum burmanii extract and 10 parts of Scutellaria baicalensis extract; Alternatively, the antidepressant composition comprises, by weight, 5 parts of Ageratum cochinchinensis extract, 5 parts of Cinnamomum burmanii extract and 5 parts of Scutellaria baicalensis extract; Alternatively, the antidepressant composition comprises, by weight, 2 parts of Ageratum cochinchinensis extract, 4 parts of Cinnamomum burmanii extract and 8 parts of Scutellaria baicalensis extract.

9. Use of the antidepressant composition according to any one of claims 1 to 8 in preventing and / or treating nervous system diseases.

10. A compound preparation, characterized in that: The antidepressant composition comprises the antidepressant composition according to any one of claims 1 to 8.

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