阅读说明：本技术 植物提取物在抗产褥期精神综合症药物中的应用 (Application of plant extract in medicine for resisting puerperal mental syndrome ) 是由 姜德建 石镇港 李明丹 王小青 于 2020-11-18 设计创作，主要内容包括：本发明涉及栀子与迷迭香提取物在抗产褥期精神综合症药物中的应用。所述栀子与迷迭香提取物制备方法包括以下步骤：由迷迭香、栀子提取物按照4:(1-9)比例组成,其中迷迭香与栀子晒干用中药粉碎机粉碎后过筛,采用料液比1g:(10-20)ml,超声提取,60℃下水或50%乙醇提取40-60分钟,浓缩得浸膏,残渣按料液比1g:(50-10)ml同样条件下提取30分钟,浓缩得浸膏,合并两次浸膏,得栀子与迷迭香水提取物。本发明制备的提取物相比与抗抑郁的西药和抗狂躁的西药,具备良好的抗产褥期精神综合症作用,表明提取物具备较好的应用前景。(The invention relates to application of gardenia and rosemary extracts in a medicament for resisting puerperal mental syndrome. The preparation method of the gardenia and rosemary extracts comprises the following steps: the rosemary and the gardenia extract are prepared according to the ratio of 4 (1-9), wherein the rosemary and the gardenia are dried and crushed by a traditional Chinese medicine crusher and then sieved, the materials and the liquid are mixed according to the ratio of 1g to 1g (10-20) ml, ultrasonic extraction is carried out, water or 50% ethanol is extracted at 60 ℃ for 40-60 minutes, extract is obtained by concentration, residues are extracted for 30 minutes under the same condition according to the ratio of 1g to 1g (50-10) ml, extract is obtained by concentration, and the extracts of the two times are combined to obtain the gardenia and rosemary perfume extract. Compared with an anti-depression western medicine and an anti-mania western medicine, the extract prepared by the invention has good effect of resisting puerperal mental syndrome, and shows that the extract has better application prospect.)

1. The application of the plant extract in the medicine for resisting puerperal mental syndrome is characterized in that the plant extract is a mixed water extract or an alcohol extract of rosemary and gardenia.

2. The use according to claim 1, wherein the puerperal mental syndrome is mental and behavioral disorders manifested in women as anxiety, mania, confusion, acute hallucinations and delusions during puerperal periods.

3. The use of claim 1, wherein the raw material of the plant extract comprises rosemary and gardenia according to a mass ratio of 4 (1-9).

4. The use of claim 3, wherein the plant extract comprises rosemary extract and gardenia extract in a mass ratio of 4 (3-7).

5. The use of claim 3, wherein the plant extract comprises rosemary extract and gardenia extract in a mass ratio of 4: 5.

6. Use according to any one of claims 1 to 5, wherein the plant extract is prepared by a process comprising the steps of:

sun drying herba Rosmarini officinalis and fructus Gardeniae, pulverizing, sieving, ultrasonic extracting, extracting with water or ethanol at 40-60 deg.C for 40-60 min, concentrating to obtain extract, extracting residue under the same conditions for 30-50 min, concentrating to obtain extract, and mixing the two extracts.

7. The use as claimed in claim 6, wherein rosemary and gardenia are dried, crushed and sieved, and the mixture ratio of the rosemary to the gardenia is 1g: 15ml of ultrasonic extraction is carried out, the mass concentration of ethanol used for extraction is 30-50%, and the residue is prepared by mixing the following raw materials in a ratio of 1g to liquid: 7ml for 30 minutes.

8. Use of a plant extract in combination with a dietary acceptable ingredient in a composition for the treatment of puerperal mental syndrome as claimed in claim 1; the composition is characterized in that the plant extract and other dietary acceptable components form a composition which is a dairy product, a compressed dry grain, a baked food, a soft drink, a sports drink, a fruit juice, a water drink, a tea, a milk-added drink or a soup.

9. The use of claim 8, wherein the dietetically acceptable ingredient is a food material that is not contraindicated for rosemary and gardenia.

10. The use of a plant extract and pharmaceutically acceptable ingredients in the composition according to claim 1 for treating puerperal mental syndrome, wherein the composition of the plant extract and other pharmaceutically acceptable ingredients is capsule, granule, tablet, pill, microcapsule, injection, suppository, spray, ointment, sustained release preparation, or controlled release preparation.

Technical Field

The invention relates to an application of a plant extract in a medicament for resisting puerperal mental syndrome.

Background

Puerperal mental syndrome refers to mental and behavioral disorders such as obvious anxiety, mania and the like in puerperal period of women, is one of the most serious disabling diseases affecting women, usually occurs within 6 weeks after delivery, and has common clinical symptoms: sadness, depression, crying, autism, anxiety, fear, irritability, etc., mental disorder, acute hallucinations, delusions, etc., and even suicidal tendency or behavior that injures the infant. Unlike traditional mania and depression, puerperal mental syndrome is usually the simultaneous occurrence of multiple mental disorders. The current methods for treating puerperal mental syndrome are psychotherapy and antipsychotic medication. The common clinical antipsychotics are classified as typical antipsychotics such as: chlorpromazine, haloperidol, etc. (the former has strong effect but strong cardiovascular and hepatic toxicity and large dosage, and the latter has small cardiovascular and hepatic toxicity but small curative effect); atypical antipsychotics: clozapine, risperidone, olanzapine, etc. (there are extrapyramidal reactions, excessive poisoning, etc.).

CN110679697A relates to rosemary compressed tea and a preparation method thereof, wherein the rosemary compressed tea comprises the following raw materials: rosemary, olive leaf, kudzu root, acanthopanax, mulberry leaf, lotus leaf, burdock root, syringa pubescens, persimmon leaf, ginkgo, gardenia jasminoides leaf, rice dumpling leaf and sea buckthorn. The rosemary compressed tea has the effects of tranquilizing and restoring consciousness, and has certain curative effect on dyspepsia and stomachache. The compressed rosemary tea has the effects of calming and promoting urination, can be used for treating various diseases such as insomnia, palpitation, headache, dyspepsia and the like, and also has the effects of strengthening the heart, promoting metabolism, promoting blood circulation of peripheral blood vessels and the like. The traditional Chinese medicine composition can also improve the disorders in the aspects of language, vision and hearing, enhance the attention, treat rheumatalgia, strengthen the liver function, reduce the blood sugar, is beneficial to the treatment of arteriosclerosis, helps the paralytic limbs recover the activity, and has good commercial prospect.

CN2019100554359A provides a traditional Chinese medicine composition for treating depression, which is prepared from the following raw material medicines in parts by weight: 10-20 parts of angelica sinensis, 10-30 parts of radix paeoniae alba, 9-15 parts of radix bupleuri, 10-15 parts of wine scutellaria baicalensis, 9-15 parts of gardenia, 10-30 parts of fermented soya beans, 10-15 parts of schisandra chinensis, 10-20 parts of radix ophiopogonis, 10-15 parts of green lily, 20-30 parts of concha amethystoides, 20-30 parts of spina date seeds, 20-30 parts of tuber fleeceflower stems, 20-30 parts of blighted wheat, 6-10 parts of Chinese dates and 6-10 parts of honey-fried licorice roots. The traditional Chinese medicine composition is used for treating depression, and is also combined with other antidepressants to prepare a combined medicine for treating depression.

CN110664965A discloses a composition for treating sleep disorder caused by depression or anxiety and a preparation method thereof. A composition for treating sleep disorders caused by depression or anxiety comprising the following ingredients: vinegar processed bupleuri radix, vinegar processed rhizoma Cyperi, cortex Albizziae, caulis Polygoni Multiflori, cortex moutan, fructus Gardeniae preparata, Coptidis rhizoma cortex Cinnamomi, rhizoma Ligustici Chuanxiong, rhizoma anemarrhenae, radix Curcumae, cortex et radix Polygalae, Os Draconis, parched semen Ziziphi Spinosae, semen Platycladi and Zhubo beef heart. The composition can well relieve sleep disorder caused by anxiety and depression, so that patients can fundamentally relieve the problem, and no side effect is caused to human bodies.

However, since puerperium mental syndrome is different from simple anxiety and depression, the prior art does not provide the application of the plant extract in the aspect of medicaments for treating the puerperium mental syndrome.

Disclosure of Invention

The invention aims to disclose an application of a plant extract in a drug for resisting puerperal mental syndrome, wherein the plant extract is a mixed extract of rosemary and gardenia.

In order to achieve the purpose, the invention adopts the following technical scheme:

the application of the plant extract in the medicine for resisting puerperal mental syndrome is that the plant extract is the mixed extract of rosemary and gardenia.

The puerperal mental syndrome is mental and behavioral disorders such as obvious anxiety, mania, confusion, acute hallucination, delusions and the like of women in the puerperal period.

Preferably, the preparation method of the plant extract comprises the following steps:

the rosemary and the gardenia are composed according to the mass ratio of 4 (1-9), wherein the rosemary and the gardenia are dried and crushed by a traditional Chinese medicine crusher and then sieved, and the material-liquid ratio is 1g: (10-20) ml, extracting by ultrasonic, extracting by water or 50% ethanol at 40-60 ℃ for 40-60 minutes, concentrating to obtain an extract, and mixing the residues according to the ratio of material to liquid of 1g: (5-10) ml of the extract is extracted for 30 minutes under the same condition, the extract is obtained by concentration, and the two extracts are combined.

Preferably, the rosemary extract and the gardenia extract are composed according to the proportion of 4 (3-7).

Preferably, the rosemary extract and the gardenia extract are prepared according to the proportion of 4: 5.

Preferably, the rosemary and the gardenia are dried and crushed by a traditional Chinese medicine crusher and then sieved, wherein the material-liquid ratio is 1g: 15ml of ultrasonic extraction.

Preferably, the ratio of the residue to the liquid is 1g: 7ml of the extract was extracted under the same conditions for 30 minutes.

The invention also provides application of the composition formed by the plant extract and other dietary or pharmaceutically acceptable components in resisting puerperal mental syndrome.

Preferably, the dietary acceptable component is a food material which is not contraindicated to the rosemary extract and the gardenia extract.

Preferably, the plant extract and other dietary or pharmaceutically acceptable ingredients form a composition to be prepared into an oral dosage form.

Preferably, the plant extract and other dietary acceptable ingredients comprise a composition in the form of a dairy product, a compressed cereal bar, a baked good, a soft drink, a sports drink, a fruit juice, a water drink, a tea, a milk-added drink or a soup.

Preferably, the pharmaceutically acceptable component is any one or more pharmaceutically acceptable excipients.

Preferably, the composition of the plant extract and other pharmaceutically acceptable ingredients can be capsules, tablets, pills, microcapsule preparations, injections, suppositories, sprays, ointments, sustained-release preparations and controlled-release preparations.

Preferably, to enable the above dosage form to be realized, various carriers well known in the art can be widely used. Examples of carriers are, for example, diluents and absorbents, such as starch, dextrin, calcium sulfate, kaolin, microcrystalline cellulose, aluminum silicate and the like; wetting agents and binders such as water, glycerin, polyethylene glycol, ethanol, propanol, starch slurry, dextrin, syrup, honey, glucose solution, acacia slurry, gelatin slurry, sodium carboxymethylcellulose, shellac, methyl cellulose, potassium phosphate, polyvinylpyrrolidone and the like; disintegrating agents such as dried starch, alginate, agar powder, brown algae starch, sodium bicarbonate and citric acid, calcium carbonate, polyoxyethylene sorbitol fatty acid ester, sodium dodecylbenzenesulfonate, methyl cellulose, ethyl cellulose, etc.; disintegration inhibitors such as sucrose, glyceryl tristearate, cacao butter, hydrogenated oil and the like; absorption promoters such as quaternary ammonium salts, sodium dodecylbenzenesulfonate, etc.; lubricants, such as talc, silica, corn starch, magnesium stearate, boric acid, liquid paraffin, polyethylene glycol, and the like; suspending agents, such as polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropylmethylcellulose, and the like; sweetening agents, such as sodium saccharin, aspartame, sucrose, sodium cyclamate and the like; preservatives, such as parabens, benzoic acid, sodium benzoate, sorbic acid and its salts, benzalkonium bromide, chloroacetidine acetate, eucalyptus oil, and the like; matrix such as PEG6000, PEG4000, insect wax, etc.

Preferably, the administration mode of the plant extract and other pharmaceutically acceptable ingredients composing the composition is injection, oral administration, parenteral administration, inhalation spray or transdermal administration.

The invention is further explained below:

the iridoid compound which is the main component of the gardenia has pharmacological activities of protecting the liver, tranquilizing, easing pain, resisting oxidation and the like, the rosemary is a plant which is generally accepted at present and has high antioxidation, the main component of the rosemary has pharmacological activities of resisting oxidation, protecting neuron cells, calming the nerves, restoring consciousness and the like, the mixed extract of the gardenia and the rosemary using a specific proportion and a specific extraction method can enhance the anti-anxiety and anti-mania curative effects, and the extracted effective components are probably in a larger relation with the main components for resisting depression in the prior art under the specific proportion and the specific extraction condition, and meanwhile, the main pharmacological active components of the gardenia and the rosemary are very likely to play unexpected synergistic effect under the proportion.

Compared with the prior art, the invention has the advantages that:

the invention proves that the gardenia and rosemary extracts have the effect of treating puerperal mental syndrome for the first time, can obviously reduce behavioral disorders such as anxiety, mania and the like of the rat puerperal mental syndrome, and has obvious difference compared with a model control group.

Detailed Description

In order to make the purpose, technical solutions and advantages of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, which are some, but not all, of the embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

The following examples used 66 female SD rats, purchased from slyke scenda laboratory animals ltd, Hunan, and the laboratory animals producing license numbers: SCXK (Xiang) 2011-: SYXK (xiang) 2015-.

Example 1

Preparation of rosemary and cape jasmine extract

Combining rosemary and gardenia according to different proportions, drying in the sun, crushing by using a traditional Chinese medicine crusher, sieving by using a 60-mesh sieve, and mixing the raw materials according to a material-liquid ratio of 1g: 15ml, 100W ultrasound assisted, water extraction for 40-60 minutes at 60 ℃, concentration to obtain extract, residue according to the material-liquid ratio of 1g: 7ml of the extract is extracted for 30 minutes under the same condition, the extract is obtained by concentration, and the two extracts are combined to obtain the rosemary extract and the gardenia extract. The different combination ratios of rosemary and gardenia are as follows:

combination 1: the rosemary extract and the gardenia extract are mixed according to the proportion of 4:7

And (3) combination 2: the rosemary extract and the gardenia extract are prepared according to the proportion of 4:5

And (3) combination: the rosemary extract and the gardenia extract are mixed according to the proportion of 4:3

Example 2

Efficacy verification of drug combination for resisting puerperal mental syndrome

(1) Mother-infant separation combined chronic unpredictable stress puerperium mental syndrome model establishment

66 healthy SD female rats are adaptively fed with one cage for parturition at pregnancy period 16-17 d. Marking production as D0, D1-D28 as 09 a.m. daily: 00 taking out a mother mouse, placing the mother mouse in an isolation cage for 3 hours, normally feeding the feed and water, enabling the isolation cage and a mother mouse original mouse cage to be in a same room, enabling the mother mouse to hear the sound of the child mouse, smell the smell of the child mouse and apply chronic unpredictable stress, wherein the chronic unpredictable stress comprises restraint for 2 hours, tail clamping for 5 minutes, stroboscopic for 12 hours, forced swimming for 10 minutes, noise for 30 minutes, fasting for 12 hours, water prohibition for 12 hours, day and night reversal and the like.

TABLE 1 Chronic unpredictable stress Schedule

Time	Stress mode
		Monday	Bound for 2h
Tuesday	Fasting and water deprivation for 12h
		Wednesday	Night and day reversal plus forced swimming for 10min
Thursday	Noise 30min + tail clamping 5min
		Friday of week	Bound for 2h
Saturday	Forced swimming for 10min + fasting for 24h
		Sunday	Noise of 30min + water supply prohibition of 24h

(2) Grouping and administration of drugs

Before modeling, the rats are randomly divided into a normal control group, a model control group, a fluoxetine hydrochloride group (an antidepressant western medicine positive control group), a sodium valproate group (an anti-maniac western medicine positive control group), a gardenia extract group, a rosemary extract group, a medicine combination 1, 2 and 3 groups and a medicine combination 2 group low, medium and high dose group, 6 groups are used, modeling is not performed on the normal control group, during modeling, the normal control group and the model control group are filled with corresponding liquid medicines every day, the administration volume is 10ml/kg, after last administration, the open field experiment detection and the elevated cross maze detection are respectively performed.

(3) Dose setting

The low, medium and high dosages of the pharmaceutical composition are set to be 50mg/kg, 100mg/kg and 150 mg/kg. The daily clinical dose of the fluoxetine hydrochloride tablet is 20mg, and the dose converted into the rat dose according to the animal and human clinical dose is as follows: 20mg 0.018/0.2 kg-1.8 mg/kg, a clinically equivalent dose of 2-fold, i.e. 3.6mg/kg, was used as the rat dose. The clinical dosage of the sodium valproate tablet is 15mg/kg, and the rat dosage is converted according to the animal and human clinical dosage: 15mg/kg 60kg 0.018/0.2kg 81mg/kg, the clinically equivalent dose was 2-fold, i.e. 162mg/kg, as the dose administered to the rats. See table 2 for details.

TABLE 2 Experimental groups and dose design

(4) Statistical method

Statistical analysis was performed using SPSS16.0 with the level of statistical significance set to P<0.05, the average plus or minus standard deviation is adopted for the measurement dataShowing that the method of Leven's test is used to check the normality and the homogeneity of variance, if the normality and the homogeneity of variance (P) are met>0.05), statistical analysis was performed using one-way analysis of variance (ANOVA) and LSD test; if the normality and homogeneity of variance are met (P.ltoreq.0.05), the Kruskal-Wallis Test is used, and if the Kruskal-Wallis Test is statistically significant (P.ltoreq.0.05), the Dunnett's Test is used for comparative analysis, taking into account the statistical differences and the biological significance in the evaluation.

(5) Detecting the index

1. Open field experiment

After the last administration, the animals are put into a test box, the detection is started after the animals are adapted for 3min, the spontaneous activity of the rats is detected within 10min, and the total movement distance within 10min is observed and recorded through a monitor.

2. Elevated cross maze

After the last administration, the spontaneous activity of the rats was observed within 5min, the arms were closed to the side of the rat head in the central area of the maze, timed for 5min, and the observation was started and recorded. After the test was completed, each rat was cleaned of feces and the instrument was wiped with 75% alcohol to eliminate the smell of the previous rat. Observation indexes are as follows: open arm entry (OE), based on entry of both rat's front paws into the arm, and complete withdrawal of both front paws from the arm, considering that the entry activity is complete, open arm retention time (OT); the determination method of the number of times of entry (CE) of the closed arm is the same as that of the open arm; closed arm dwell time (CT); and calculating the percentage of open arm entry times: OE% ═ OE/(OE + CE) × l 00; percent open arm residence time: OT% — OT/(OT + CT) × 100%.

(6) Results of the experiment

1. Influence of different drug combinations on autonomic activity of puerperal mental syndrome rats and elevated plus maze experimental data

As shown in table 3, compared with the normal control group, the total distance of autonomous activity of the model control group is significantly increased, and the OE% and the OT% are significantly reduced (P < 0.01); compared with a model control group, the total course of fluoxetine hydrochloride group (antidepressant western medicine positive control group) is obviously increased, and the total course of autonomic activity of other administration groups is obviously reduced (P <0.05 or P < 0.01). The results show that the anti-maniac drug sodium valproate and the pharmaceutical composition for the rats with the manic syndrome in the puerperium can effectively reduce the manic behavior, and the antidepressant drug fluoxetine hydrochloride can aggravate the manic behavior of the rats with the manic syndrome in the puerperium. Particularly, the total course of the high-dose group of the medicine combination 2 is even lower than that of the sodium valproate group, so that the manic behavior of the hyponatremia manica rats in the puerperium period is reduced and is even better than that of the anti-manic western medicine control group.

Compared with a normal control group, the OE% and OT% of the model control group are obviously reduced (P < 0.01); compared with a model control group, the sodium valproate group (an anti-maniac western medicine positive control group), the drug combination 2 middle and high dose group OE% and OT% are obviously increased (P <0.01), the drug combination low dose group OT% and fluoxetine hydrochloride group (an anti-depression western medicine positive control group) OE% are obviously increased (P < 0.05). The results show that fluoxetine hydrochloride, sodium valproate, the pharmaceutical composition and the single gardenia extract and rosemary extract can effectively relieve anxiety behaviors of rats with mental syndromes in puerperium.

TABLE 3 combination of different drugs for autonomic activity and elevated cross in puerperium mental syndrome ratInfluence of uterine Experimental data

Note: (ii) + P <0.05, + + P <0.01, as compared to a normal control group; p <0.05, P <0.01 compared to model control group.

The behavioral results show that the combination of gardenia and rosemary has better behavioral effects on relieving anxiety, mania and the like of rats than the relief effects of gardenia or rosemary extract alone, and the effect of the medicine combination 2 is better than that of other combinations.

The extract of the medicinal composition can obviously reduce the exercise of the mania-like rats with the puerperal mental syndromes, the antidepressant fluoxetine hydrochloride tablet has opposite effects on the mania-like rats with the puerperal mental syndromes, and the high dose of the medicinal composition can obviously increase OE% and OT% of the elevated plus maze experiments of the rats with the puerperal mental syndromes. Although sodium valproate has a good therapeutic effect on mania and anxiety attacks, the sodium valproate can permeate the placenta barrier to have potential teratogenic risks, so that the sodium valproate has contraindications for pregnant women and lactating women. In conclusion, the medicine combination 2 group has very good effect of resisting mania and anxiety of puerperal mental syndrome, and can be safely used.

In addition, the extract of the present invention is not limited to the aqueous extraction method described in the examples, and 50% alcohol extract can achieve the same effect. In addition, similar solvent extraction methods can achieve similar effects when adjusting the dosage, and should be considered to be within the scope of the present invention.