CN116159101A - Traditional Chinese medicine composition and preparation method and application thereof - Google Patents
Traditional Chinese medicine composition and preparation method and application thereof Download PDFInfo
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- CN116159101A CN116159101A CN202211651320.4A CN202211651320A CN116159101A CN 116159101 A CN116159101 A CN 116159101A CN 202211651320 A CN202211651320 A CN 202211651320A CN 116159101 A CN116159101 A CN 116159101A
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Classifications
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- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
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- A—HUMAN NECESSITIES
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- A61K2236/30—Extraction of the material
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K2236/50—Methods involving additional extraction steps
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Landscapes
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- Life Sciences & Earth Sciences (AREA)
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- General Health & Medical Sciences (AREA)
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- General Chemical & Material Sciences (AREA)
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- Molecular Biology (AREA)
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Abstract
The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition, and a preparation method and application thereof. In order to improve the quality, stability, safety and effectiveness of the traditional Chinese medicine prescription, the invention provides a traditional Chinese medicine composition with a therapeutic effect on depression on the basis of classical prescription yippee powder, and provides a preparation method of the composition, and animal experiment results show that: the composition provided by the invention can obviously shorten the forced swimming immobility time and tail suspension immobility time of a depression model mouse, and can obviously prolong the times and the time percentage of the mouse entering an open arm. The composition provided by the invention has a significantly better effect than classical prescription Happy powder in the aspect of treating depression patients, has significantly reduced toxic and side effects, and has important development and application values.
Description
Technical Field
The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition, and a preparation method and application thereof.
Background
The classical prescription Happy powder consists of polygala tenuifolia, ginseng, poria cocos and grassleaf sweelflag rhizome, is a representative prescription for tonifying qi and nourishing heart, soothing nerves and stabilizing mind, and is mainly used for treating heart qi deficiency, restlessness, amnesia and insomnia, heart shAN_SNe and the like, which is originally seen in the fourteenth volume (small intestine Fu) of Sunshan Ji Qianjin Fang (Confucius of first-aid). Wherein ginseng has the functions of invigorating primordial qi, soothing nerves and tonifying qi, and poria cocos has the functions of strengthening spleen and reducing phlegm, calming heart and soothing nerves, and promoting diuresis and removing dampness as auxiliary materials; rhizoma Acori Graminei has effects of resolving phlegm, inducing resuscitation, nourishing viscera, and refreshing; polygala tenuifolia calms the heart and tranquilizes the mind, eliminates phlegm and opens orifices, and can be combined with calamus to strengthen the effect of eliminating phlegm and opening orifices, and poria cocos to calm the heart and kidney and calm the nerves and promote intelligence. The four medicines have mild medicine properties and have the effects of nourishing the heart, soothing the nerves and improving the intelligence, and the medicine selection is accurate; the whole formula is mainly used for tonifying, strengthening middle-jiao and reducing diarrhea, simultaneously has the effects of resolving phlegm and inducing resuscitation, has strict compatibility, treats the traditional Chinese medical emotional diseases such as heart qi deficiency, restlessness, anxiety, insomnia, depression and severe palpitation, is similar to the depression of Western medicine, and is a basic prescription for improving intelligence, nourishing heart and soothing nerves and stabilizing mind in traditional Chinese medicine.
Anxiety and depressive disorders are mental diseases that seriously threaten the health of people, and recent research data indicate that the incidence rate of anxiety disorders in the elderly is as high as 10%, the incidence rate of anxiety disorders in the general population is also as high as 2% -5%, the incidence rate of depression in the young is about 2%, and the incidence rate of anxiety disorders is gradually increasing with the age. Most patients have anxiety and depression co-morbid conditions. At present, western medicines are still mainly used for treating depression, and the western medicines are from a single target point, so that the defects of narrow anti-depression spectrum, slow onset of action and large side effect are commonly existed. The traditional Chinese medicine has the characteristics of multiple components, small toxic and side effects, multiple effects, strong synergistic effect and overall regulation, and has unique advantages in the treatment of depression. However, due to the limitations of the complexity, scientific and technical conditions, research ideas, methods and other factors of the traditional Chinese medicine, the quality, stability, safety and effectiveness of the traditional Chinese medicine composition cannot be ensured. This becomes a key constraint factor for the traditional Chinese medicine to exert the effect of treating diseases.
Disclosure of Invention
In order to solve the problems of stability, safety, effectiveness and the like of the traditional Chinese medicine prescription (Happy powder) when being used for treating diseases, the invention takes the traditional Chinese medicine prescription compatibility and the theory related to prescription symptoms as guidance, and based on the internal relation of 'components-drug effects', the effective component group in the traditional Chinese medicine prescription preparation is determined by separating and extracting natural products and carrying out a series of pharmacodynamic screening and safety evaluation, and the traditional Chinese medicine composition with the prevention and treatment effect on depression is provided, and comprises the following four active components: ginsenoside, tenuifolin, rhizoma acori graminei water extraction and alcohol precipitation liquid and poria cocos micropowder.
Wherein the ginsenoside is protopanaxadiol and protopanaxatriol.
The active ingredients are as follows according to weight percent:
1-10 parts of ginsenoside and 1-10 parts of tenuifolin
10-100 parts of rhizoma acori graminei water extraction and alcohol precipitation liquid and 200-2000 parts of poria cocos micropowder
Preferably, it is:
ginsenoside 3 parts and senega saponin 2 parts
40 parts of glabrous greenbrier rhizome water extraction and alcohol precipitation liquid and 1200 parts of poria cocos micropowder
The preparation method of each component in the composition comprises the following steps:
the preparation method of the ginsenoside comprises the following steps:
(1) Alkaline hydrolysis reaction
Weighing total saponins of ginseng stem and leaf, and weighing total saponins (g) of ginseng stem and leaf: adding sodium hydroxide into the mixture according to the weight ratio of 1:1-1:4 of sodium hydroxide (g), adding small steel mill powder, uniformly mixing, transferring to a vacuum drying oven, reacting for 4-24h at the normal pressure of 100-240 ℃ to obtain an alkaline hydrolysis reactant, standing and cooling;
(2) Silica gel mixing material
Weighing silica gel with the total amount of 2-10 times, adding 630-4410 ml of absolute ethyl alcohol, uniformly stirring with the alkaline hydrolysis reactant obtained in the step (1), and naturally airing or evaporating in a vacuum rotary manner;
(3) Extraction of
Adding ethyl acetate (ml) into the silica gel stirring material in the step (2) according to the amount of 1:5-1:20, reflux-extracting for 1h at 80 ℃ for 2 times, and mixing to obtain a total extract;
(4) Concentrating and drying
Concentrating the extract obtained in the step (3) under reduced pressure to dryness, and drying in a vacuum drying oven to obtain the ginsenoside extract.
Preferably:
the preparation method of the ginsenoside comprises the following steps:
(1) Alkaline hydrolysis reaction
Weighing total saponins of ginseng stem and leaf, adding sodium hydroxide with the weight being 2 times that of the total saponins, adding small steel mill powder, uniformly mixing, transferring to a vacuum drying oven, setting the temperature at 170 ℃ at normal pressure, reacting for 12 hours to obtain alkaline hydrolysis reactants, standing and cooling;
(2) Silica gel mixing material
Weighing silica gel 7 times of the total amount of the materials, adding 2000ml of absolute ethyl alcohol, uniformly stirring with the alkaline hydrolysis reactant obtained in the step (1), and naturally airing or evaporating in a vacuum rotary manner;
(3) Extraction of
Adding ethyl acetate (ml) into the silica gel mixture in the step (2) according to the amount of 1:7, reflux-extracting for 1h at 80 ℃ for 2 times, and mixing to obtain a total extract;
(4) Concentrating and drying
Concentrating the extract obtained in the step (3) under reduced pressure to dryness, and drying in a vacuum drying oven to obtain the ginsenoside extract. The preparation method of the tenuifolin comprises the following steps:
(1) Decocting and extracting with water: weighing radix Polygalae, extracting with drinking water, mixing the water extracts, and concentrating to obtain concentrated solution;
(2) Alkaline hydrolysis: adding alkali into the concentrated solution for alkaline hydrolysis to obtain alkaline hydrolysis solution;
(3) Alcohol precipitation: adjusting the pH of the alkaline hydrolysis solution obtained in the step (2) to 4-5 by using acid, adjusting the alcohol degree to 70-90% by using absolute ethyl alcohol, filtering, and collecting filtrate;
(4) And (3) water sedimentation: concentrating the filtrate collected in the step (3) until no alcohol smell exists, adding drinking water for water precipitation, centrifugally collecting a precipitation part, and drying to obtain a crude tenuifolin;
(5) And (3) crystallization: recrystallizing the crude tenuifolin obtained in the step (4) to obtain tenuifolin.
Preferably:
the preparation method of the tenuifolin comprises the following steps:
(1) Decocting and extracting with water: weighing radix Polygalae, adding 10 times of drinking water, extracting for 3 times and 4 hr each time, mixing the water extractive solutions, and concentrating to obtain concentrated solution;
(2) Alkaline hydrolysis: adding alkali into the concentrated solution obtained in the step (1) until the concentration is 10%, and performing alkaline hydrolysis for 3 hours to obtain alkaline hydrolysis solution;
(3) Alcohol precipitation: and (3) regulating the pH value of the alkaline hydrolysis liquid obtained in the step (2) to 4-5 by using concentrated hydrochloric acid. Regulating alcohol degree to 70-90% with absolute ethyl alcohol, filtering and collecting filtrate;
(4) And (3) water sedimentation: concentrating the filtrate collected in the step (3) until no alcohol smell exists, adding 40L of drinking water into each kilogram of medicinal material for water precipitation, centrifugally collecting a precipitation part, and drying to obtain a crude tenuifolin;
(5) And (3) crystallization: reflux-recrystallizing the crude tenuifolin obtained in the step (4) with absolute ethanol to obtain tenuifolin.
The preparation method of the water extraction and alcohol precipitation solution of the grassleaf sweelflag rhizome comprises the following steps:
(1) Extraction of
Weighing 200g of rhizoma acori graminei decoction pieces, adding 10 times of drinking water for 2L, reflux-extracting for 2h, extracting for 2 times, and merging the extracting solutions after the extraction is finished;
(2) Concentrating
Concentrating the extract obtained in step (1) to about 0.5g/ml;
(3) Alcohol precipitation
Regulating the concentrated solution obtained in the step (2) to 70% of alcohol by using edible alcohol, and precipitating the alcohol overnight to obtain an alcohol precipitation solution;
(4) Filtration
Filtering the alcohol precipitation liquid obtained in the step (3), and reserving filtrate.
(5) Concentrating and drying
Concentrating the filtrate obtained in the step (4) under reduced pressure, drying to obtain rhizoma Acori Graminei extract, and drying in a vacuum drying oven.
The preparation method of the poria cocos micro powder comprises the following steps:
(1) Washing Poria with water, drying in oven at 40-60deg.C, pulverizing in high speed pulverizer, and sieving with 80 mesh sieve to obtain Poria coarse powder.
(2) Pulverizing Poria coarse powder obtained in step (1) with jet mill under compressed air pressure of 0.4-0.6Kpa and feeding speed of 0.5-10kg/h to obtain Poria micropowder, and analyzing the particle size distribution of Poria micropowder with laser particle size distribution analyzer to obtain D90<20um.
The anti-depression effect research is carried out on the traditional Chinese medicine composition, and the experimental result shows that: the traditional Chinese medicine composition can obviously shorten the forced swimming immobility time and tail suspension immobility time of a depressive mouse, and each effective component in the composition has obvious synergistic effect when the antidepressant effect is exerted, and the effect of the composition on treating the depressive is obviously better than the treatment effect of classical famous prescription yippee powder on the depressive.
Toxicity test results show that: compared with the classical prescription Happy powder, the composition provided by the invention has obviously reduced toxicity, is mainly characterized by good animal general condition, and obviously reduces the incidence rate of gastrointestinal bleeding and the death rate of animals.
The composition can be prepared into a pharmaceutical preparation, and the pharmaceutical preparation can contain pharmaceutically acceptable auxiliary materials besides the composition provided by the invention.
The pharmaceutical formulations include, but are not limited to, tablets, capsules, granules or pills.
The composition provided by the invention has the following advantages in treating depression:
1. compared with the classical prescription Happy powder, the traditional Chinese medicine powder has the advantages of enriching effective active ingredients, improving the bioavailability of medicinal substances and remarkably enhancing the treatment effect on depression.
2. The components are controllable, the toxic and side effects are less, and the components have obvious synergistic effect when treating depression.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
In order for those skilled in the art to fully understand the present invention, the present invention is further illustrated by the following specific examples, but those skilled in the art should understand that the present invention is not limited in any way.
Preparation of ginsenoside example 1
(1) Alkaline hydrolysis reaction
Weighing total saponins of ginseng stem and leaf, adding sodium hydroxide with the weight being 2 times that of the total saponins, adding small steel mill powder, uniformly mixing, transferring to a vacuum drying oven, setting the temperature at 170 ℃ at normal pressure, reacting for 12 hours to obtain alkaline hydrolysis reactants, standing and cooling;
(2) Silica gel mixing material
Weighing silica gel 7 times of the total amount of the materials, adding 2000ml of absolute ethyl alcohol, uniformly stirring with the alkaline hydrolysis reactant obtained in the step (1), and naturally airing or evaporating in a vacuum rotary manner;
(3) Extraction of
Adding ethyl acetate (ml) into the silica gel mixture in the step (2) according to the amount of 1:7, reflux-extracting for 1h at 80 ℃ for 2 times, and mixing to obtain a total extract;
(4) Concentrating and drying
Concentrating the extract obtained in the step (3) under reduced pressure to dryness, and drying in a vacuum drying oven to obtain the ginsenoside extract.
Preparation of ginsenoside example 2
(1) Alkaline hydrolysis reaction
Weighing total saponins of ginseng stem and leaf, adding sodium hydroxide with the same weight, adding small steel mill powder, mixing uniformly, transferring to a vacuum drying oven, setting at normal pressure and reacting at 100 ℃ for 4 hours to obtain alkaline hydrolysis reactant, standing and cooling;
(2) Silica gel mixing material
Weighing silica gel with the total amount being 2 times that of the materials, adding 630ml of absolute ethyl alcohol, uniformly stirring with the alkaline hydrolysis reactant obtained in the step (1), and naturally airing or evaporating in a vacuum rotary manner;
(3) Extraction of
Adding ethyl acetate (ml) into the silica gel mixture in the step (2) according to the amount of 1:5, reflux-extracting for 1h at 80 ℃ for 2 times, and mixing to obtain a total extract;
(4) Concentrating and drying
Concentrating the extract obtained in the step (3) under reduced pressure to dryness, and drying in a vacuum drying oven to obtain the ginsenoside extract.
Preparation of ginsenoside example 3
(1) Alkaline hydrolysis reaction
Weighing total saponins of ginseng stem and leaf, adding sodium hydroxide with the weight being 4 times that of the total saponins, adding small steel mill powder, uniformly mixing, transferring to a vacuum drying oven, setting 240 ℃ at normal pressure, reacting for 24 hours to obtain alkaline hydrolysis reactant, standing and cooling;
(2) Silica gel mixing material
Weighing silica gel 10 times of the total amount of the materials, adding 4410ml of absolute ethyl alcohol, uniformly stirring with the alkaline hydrolysis reactant obtained in the step (1), and naturally airing or evaporating in a vacuum rotary manner;
(3) Extraction of
Adding ethyl acetate (ml) into the silica gel mixture in the step (2) according to the amount of 1:20, reflux-extracting for 1h at 80 ℃ for 2 times, and mixing to obtain a total extract;
(4) Concentrating and drying
Concentrating the extract obtained in the step (3) under reduced pressure to dryness, and drying in a vacuum drying oven to obtain the ginsenoside extract.
Preparation of ginsenoside example 4
(1) Alkaline hydrolysis reaction
Weighing total saponins of ginseng stem and leaf, adding sodium hydroxide with the weight being 2 times that of the total saponins, adding small steel mill powder, uniformly mixing, transferring to a vacuum drying oven, setting 240 ℃ at normal pressure, reacting for 12 hours to obtain alkaline hydrolysis reactant, standing and cooling;
(2) Silica gel mixing material
Weighing silica gel 10 times of the total amount of the materials, adding 3000ml of absolute ethyl alcohol, uniformly stirring with the alkaline hydrolysis reactant obtained in the step (1), and naturally airing or evaporating in a vacuum rotary manner;
(3) Extraction of
Adding ethyl acetate (ml) into the silica gel mixture in the step (2) according to the amount of 1:7, reflux-extracting for 1h at 80 ℃ for 2 times, and mixing to obtain a total extract;
(4) Concentrating and drying
Concentrating the extract obtained in the step (3) under reduced pressure to dryness, and drying in a vacuum drying oven to obtain the ginsenoside extract.
Preparation of tenuifolin example 1
Taking polygala tenuifolia medicinal materials, adding 10 times of drinking water into the medicinal materials, heating, refluxing and extracting for 4 hours, extracting for 3 times, merging and concentrating the extracting solution into clear paste, adding caustic soda flakes, regulating the pH to be 4.40 by using concentrated hydrochloric acid, regulating the alcohol degree to be 80 percent by adding absolute ethanol, filtering, collecting filtrate, concentrating the filtrate until the alcohol taste is not generated (the alcohol degree is 0), adding 40L of drinking water into each kilogram of medicinal materials for water precipitation, centrifuging and collecting a precipitated part, drying to obtain crude polygala tenuifolia saponins, adding absolute ethanol, repeatedly refluxing and recrystallizing to obtain the polygala tenuifolia saponins.
Preparation example 2 of tenuifolin
Taking polygala tenuifolia medicinal materials, adding 15 times of drinking water into the medicinal materials, heating, refluxing and extracting for 2 hours, extracting for 2 times, merging and concentrating the extracting solution into clear paste, adding caustic soda, adjusting the pH to be 4.85 by phosphoric acid, adding absolute ethanol to adjust the alcohol degree to be 70 percent, filtering, collecting filtrate, concentrating the filtrate until the alcohol smell is not generated (the alcohol degree is 0), adding 25L of drinking water into each kilogram of medicinal materials for water precipitation, centrifuging and collecting a precipitated part, drying to obtain crude tenuifolin, adding methanol, repeatedly refluxing and recrystallizing to obtain the tenuifolin.
Preparation example 3 of tenuifolin
Heating and reflux-extracting radix Polygalae with 10 times of drinking water for 1 hr, extracting for 1 time, concentrating the extractive solution to obtain fluid extract, adding caustic soda, adjusting to 10%, alkaline hydrolyzing for 1 hr, adjusting p H =4.30 with acetic acid, adding absolute ethanol to adjust alcohol degree to 80%, filtering, collecting filtrate, concentrating filtrate to no alcohol taste (alcohol degree of 0), adding 25L of drinking water per kilogram of medicinal material, precipitating with water, centrifuging, collecting precipitate, drying to obtain crude fine leaf radix Polygalae saponin, adding absolute ethanol, repeatedly reflux-crystallizing to obtain fine leaf radix Polygalae saponin.
Preparation example 4 of tenuifolin
Taking polygala tenuifolia medicinal materials, adding 20 times of drinking water into the medicinal materials, heating and reflux-extracting for 2 hours, extracting for 2 times, merging and concentrating the extracting solution to obtain clear paste, adding caustic soda, adjusting to 1%, alkaline hydrolysis for 3 hours, adjusting p H =4.0 by using concentrated hydrochloric acid, adding absolute ethyl alcohol to adjust the alcohol degree to 90%, filtering, collecting filtrate, concentrating the filtrate to be free of alcohol taste (alcohol degree is 0), adding 25L of drinking water into each kilogram of medicinal materials for water precipitation, centrifugally collecting a precipitation part, drying to obtain crude polygala tenuifolia saponins, adding absolute ethyl alcohol, repeatedly refluxing and recrystallizing to obtain the polygala tenuifolia saponins.
Preparation example 5 of tenuifolin
Taking polygala tenuifolia medicinal materials, adding 20 times of drinking water into the medicinal materials, heating, refluxing and extracting for 2 hours, extracting for 2 times, merging and concentrating the extracting solution into clear paste, adding caustic soda, adjusting to 5%, alkaline hydrolyzing for 2 hours, adjusting p H =5.0 by using concentrated hydrochloric acid, adding absolute ethyl alcohol to adjust the alcohol degree to 80%, filtering, collecting filtrate, concentrating the filtrate until the alcohol smell-free measured alcohol degree is 0, adding 30L of drinking water into each kilogram of medicinal materials for water precipitation, centrifugally collecting a precipitation part, drying to obtain crude polygala tenuifolia saponins, adding methanol, repeatedly refluxing and recrystallizing to obtain the polygala tenuifolia saponins.
Composition example 1
Ginsenoside 3 parts and senega saponin 2 parts
40 parts of glabrous greenbrier rhizome water extraction and alcohol precipitation liquid and 1200 parts of poria cocos micropowder
Composition example 2
1 part of ginsenoside and 1 part of tenuifolin
10 parts of glabrous greenbrier rhizome water extraction and alcohol precipitation liquid and 200 parts of poria cocos micro powder
Composition example 3
10 parts of ginsengenin and 10 parts of tenuifolin
100 parts of glabrous greenbrier rhizome water extraction and alcohol precipitation liquid and 2000 parts of poria cocos micropowder
Composition example 4
5 parts of ginsenoside and 5 parts of tenuifolin
100 parts of glabrous greenbrier rhizome water extraction and alcohol precipitation liquid and 2000 parts of poria cocos micropowder
Examples of pharmaceutical effects of the compositions
Therapeutic effect of composition on depression model mice
1. Animal modeling and grouping
2.100 Kunming mice, copying depression model by forced swimming experiment, selecting 84 mice with successful model, and randomly dividing into 7 groups, namely model group, pistachio group, ginsenoside group, tenuifolia saponin group, rhizoma Acori Graminei water extraction and alcohol precipitation liquid group, poria micropowder group and composition group (composition example 1). Methods of administration and dosage
Happy powder group (each traditional Chinese medicine in the classical famous prescription Happy powder is crushed into powder by a high-speed crusher), and the dosage of administration is 960mg/kg
Ginsenoside group, and administration dosage is 1.5mg/kg
Polygalasaponin group with administration dosage of 1.0mg/kg
Rhizoma Acori Graminei water extraction and alcohol precipitation liquid group, and administration dosage is 20mg/kg
Poria cocos micropowder group, and administration dosage is 600mg/kg
Composition group, administration dose 622.5mg/kg
The administration volume of each group was 30ml/kg, and the model group was administered with an equal volume of physiological saline.
Each group of mice was continuously administrated by gastric lavage for two weeks according to the above dose and administration volume, after the last administration, clear water was poured into a bucket (diameter: 30cm, height: 60 cm), water depth: 40cm, water temperature: 25.+ -. 2) degree centigrade, and after the mice were put into water to be adapted for 2min, swimming immobility time within 4min was measured and accumulated. The time when the mouse body was slightly curled but kept in a hanging posture and the nostrils were exposed to the water surface was recorded as the immobile time. After the experiment of each mouse is finished, the mice are wiped dry by a towel and dried by a blower.
3. Overhead maze test
3.1 Experimental methods
The experimental mice were observed for behavioral changes using an overhead plus maze. The inner wall and the bottom surface of the overhead cross maze are dark gray, have a height of 50cm from the ground, and are formed by two opposite open arms (open arm, length x width is 45cmx15 cm), two opposite closed arms (closed arm, length x width x height is 45cm x15cm x 30cm) and a central platform (15 cmx15 cm) for connecting the four arms in a cross shape. The top of the closed arm is open and is carried out under the quiet and shading conditions. Before EPM test, the mice to be tested are placed in a squirrel cage, and after 5min of free exploration, the mice are quickly placed at the central platform of the EPM, so that the heads of the mice are opposite to any one of the open arms, and after release, the mice begin to observe the test. Each rat was tested for 5min. After the mice are taken out, the bottoms of the cases are thoroughly wiped by dipping the towels with clean water and low-concentration alcohol, and the mice are waited for volatilizing and diffusing, so that the phenomenon that odor is remained to interfere the observation result of the next mouse is avoided.
3.2 observations index
(1) Open arm entry (OE); (2) open arm dwell time (OT); (3) number of closed arm entries (CE); (4) closed arm dwell time (CT); counting the total number of entries (oe+ce) into the open and closed arms; the proportion of times of entering the open arms; open arm residence time ratio.
4. Tail suspension experiment
After the last stomach infusion, the tail part of the mouse is fixed on the edge of the rack by using the adhesive tape, so that the tail part of the mouse is in a reverse hanging state, the head part is about 5cm away from the table top, and the mice are kept at a certain distance to avoid mutual interference. After hanging the mice for 2min, observations were started for 4min, and the time(s) of immobility (stop struggling in air or only fine limb movements) of the mice was accumulated for 4 min.
5. Statistical analysis
The single-factor analysis of variance of the F test was performed using SPSS 17.0 software.
6. Experimental results
6.1 forced swimming test results
Table 1 comparison of forced swimming immobility time in groups of depressed mice
Group of | n | Swimming immobility time(s) |
Model group | 12 | 232.12 soil 22.13 |
Happy powder group | 12 | 180.24 soil 24.12 # |
Ginsenoside group | 12 | 191.56 soil 19.07 # |
Polygalasaponin group of tenuifolia | 12 | 199.27 soil 21.08 # |
Water extraction and alcohol precipitation liquid group of grassleaf sweelflag rhizome | 12 | 201.19 soil 18.92 # |
Poria cocos micropowder group | 12 | 194.45 soil 17.01 # |
Composition set | 12 | 159.27 soil 14.89 #﹩ |
Each of the administration groups was compared with the model group, # p<0.05; compared with the yippee powder and each individual component, ﹩ p<0.05。
the results show that the time for forced swimming of mice in each administration group is obviously shortened compared with a model group, wherein the time of the composition group provided by the invention is obviously shortened, and compared with a pistachio powder group and each individual component in the composition, the composition provided by the invention has obvious difference (p < 0.05), and the results show that compared with the traditional pistachio powder, the composition provided by the invention has more obvious effect on improving the depression emotion of depression patients.
6.2 elevated plus maze test results
Table 2 percent open arm number and percent open time for each group of model mice with depression
Each of the administration groups was compared with the model group, # p<0.05; compared with the yippee powder and each individual component, ﹩ p<0.05。
the results show that compared with a model group, the number and time percentage of mice entering an open arm of each administration group are obviously prolonged, wherein the composition provided by the invention has the most obvious prolonged action, and compared with a pistachio powder group and each individual component in the composition, the composition provided by the invention has obvious difference (p < 0.05), and the results show that compared with classical pistachio powder, the composition provided by the invention has obviously improved effect on the treatment of depression patients, and each component in the composition has obvious synergistic action.
6.3 tail suspension test
TABLE 3 Effect of compositions on mice tail-holding time
Group of | n | Time of immobility(s) within 4min |
Model group | 12 | 121.90 soil 12.18 |
Happy powder group | 12 | 80.94 soil 14.62 # |
Ginsenoside group | 12 | 101.35 soil 19.14 # |
Polygalasaponin group of tenuifolia | 12 | 99.38 soil 21.09 # |
Water extraction and alcohol precipitation liquid group of grassleaf sweelflag rhizome | 12 | 101.33 soil 18.17 # |
Poria cocos micropowder group | 12 | 94.38 soil 17.22 # |
Composition set | 12 | 59.47 soil 14.39 #﹩ |
Each administration group was compared with the model group, # p<0.05; compared with the yippee powder and each individual component, ﹩ p<0.05。
the results show that compared with a model group, the tail suspension time of mice in each administration group is obviously shortened, wherein the time of the composition group provided by the invention is obviously shortened, and compared with a pistachio powder group and each single component in the composition, the composition provided by the invention has obvious difference (p < 0.05), and the results show that compared with the traditional pistachio powder, the composition provided by the invention has more obvious effect on improving the depression emotion of depression patients.
The pharmacodynamic test of the compositions in composition examples 1-4 is carried out by using the experimental method in the pharmacodynamic example, and the results show that the treatment effect of each composition in composition examples 1-4 on depression is obviously better than that of the classical Happy powder.
Toxicity test
1. Experimental animal
Animal strain | ICR mice |
Sex (sex) | Male male |
Body weight/age range | 27-30 g/5 weeks |
Quantity of | 30 pieces of |
Suppliers (suppliers) | Experimental animals Breeding Limited for Jinan Pengyue |
Producing license numbers | SCXK 20190003 |
Use license number | SYXK 20180008 |
2. Grouping animals
Animals that were quarantined were randomly divided into open heart groups, low dose groups and high dose groups, and the amounts and frequency of administration of each group are shown in table 4:
TABLE 4 grouping and dosing of animals
Animals of each group were dosed continuously for four weeks according to the routes of administration indicated in the table above.
3. Observation index
3.1 general Condition observations
Daily observations and recordings of animal activity, hair color, stool and urine, abdominal distension and weighing were made during the course of administration.
3.2 gastrointestinal bleeding and death of animals
Animals were anesthetized and dissected after the last administration, gastrointestinal bleeding was observed, and mortality was counted for each group.
4. Experimental results
4.1 general Condition observations
The free-ranging mice have obviously reduced activity, dark hair color, abdominal distension, thin stool, bloody stool and the like, but the composition provided by the invention has few of the above adverse conditions, most animals are normal, and the weight of the free-ranging animals is obviously lower than that of the animals in the composition provided by the invention.
4.2 gastrointestinal bleeding and death of animals
The number of gastrointestinal bleeding occurring in animals of the composition group provided by the invention is obviously smaller than that of the Happy powder group, and no death phenomenon of animals occurs, and the specific results are shown in Table 5.
Table 5 comparison of gastrointestinal bleeding and animal death in groups of animals
Claims (6)
1. A Chinese medicinal composition is characterized in that the active ingredients of the Chinese medicinal composition comprise ginsenoside, tenuifolin, rhizoma acori graminei water extraction and alcohol precipitation liquid and poria cocos micropowder.
2. The composition of claim 1, wherein the ginsenoside is protopanaxadiol or protopanaxatriol.
3. The traditional Chinese medicine composition according to claim 1, wherein the active ingredients are as follows in weight fraction: 1-10 parts of ginsenoside and 1-10 parts of tenuifolin
10-100 parts of rhizoma acori graminei water extraction and alcohol precipitation liquid and 200-2000 parts of poria cocos micropowder
Preferably, it is:
ginsenoside 3 parts and senega saponin 2 parts
40 parts of gladiolus water extraction and alcohol precipitation liquid and 1200 parts of poria cocos micropowder.
4. A method for preparing the traditional Chinese medicine composition of claims 1-3, characterized in that the method for preparing the ginsenoside comprises the following steps:
(1) Alkaline hydrolysis reaction
Weighing total saponins of ginseng stem and leaf, and weighing total saponins (g) of ginseng stem and leaf: adding sodium hydroxide into the mixture according to the weight ratio of 1:1-1:4 of sodium hydroxide (g), adding small steel mill powder, uniformly mixing, transferring to a vacuum drying oven, reacting for 4-24h at the normal pressure of 100-240 ℃ to obtain an alkaline hydrolysis reactant, standing and cooling;
(2) Silica gel mixing material
Weighing silica gel with the total amount of 2-10 times, adding 630-4410 ml of absolute ethyl alcohol, uniformly stirring with the alkaline hydrolysis reactant obtained in the step (1), and naturally airing or evaporating in a vacuum rotary manner;
(3) Extraction of
Adding ethyl acetate (ml) into the silica gel stirring material in the step (2) according to the amount of 1:5-1:20, reflux-extracting for 1h at 80 ℃ for 2 times, and mixing to obtain a total extract;
(4) Concentrating and drying
Concentrating the extract obtained in the step (3) under reduced pressure to dryness, and drying in a vacuum drying oven to obtain a ginsenoside extract;
the preparation method of the tenuifolin comprises the following steps:
(1) Decocting and extracting with water: weighing radix Polygalae, extracting with drinking water, mixing the water extracts, and concentrating to obtain concentrated solution;
(2) Alkaline hydrolysis: adding alkali into the concentrated solution for alkaline hydrolysis to obtain alkaline hydrolysis solution;
(3) Alcohol precipitation: adjusting the pH value of the alkaline hydrolysis liquid obtained in the step (2) to 4-5 by acid,
regulating alcohol degree to 70-90% with absolute ethyl alcohol, filtering and collecting filtrate;
(4) And (3) water sedimentation: concentrating the filtrate collected in the step (3) until no alcohol smell exists, adding drinking water for water precipitation, centrifugally collecting a precipitation part, and drying to obtain a crude tenuifolin;
(5) And (3) crystallization: recrystallizing the crude tenuifolin obtained in the step (4) to obtain tenuifolin;
the preparation method of the water extraction and alcohol precipitation solution of the grassleaf sweelflag rhizome comprises the following steps:
(1) Extraction of
Weighing 200g of rhizoma acori graminei decoction pieces, adding 10 times of drinking water for 2L, reflux-extracting for 2h, extracting for 2 times, and merging the extracting solutions after the extraction is finished;
(2) Concentrating
Concentrating the extract obtained in step (1) to about 0.5g/ml;
(3) Alcohol precipitation
Regulating the concentrated solution obtained in the step (2) to 70% of alcohol by using edible alcohol, and precipitating the alcohol overnight to obtain an alcohol precipitation solution;
(4) Filtration
Filtering the alcohol precipitation liquid obtained in the step (3), and reserving filtrate.
(5) Concentrating and drying
Concentrating the filtrate obtained in the step (4) under reduced pressure, drying to obtain rhizoma Acori Graminei extract, and drying in a vacuum drying oven.
The preparation method of the poria cocos micro powder comprises the following steps: the preparation method of the poria cocos micro powder comprises the following steps:
(1) Washing Poria with water, drying in oven at 40-60deg.C, pulverizing in high speed pulverizer, and sieving with 80 mesh sieve to obtain Poria coarse powder;
(2) Pulverizing Poria coarse powder obtained in step (1) with jet mill under compressed air pressure of 0.4-0.6Kpa and feeding speed of 0.5-10kg/h to obtain Poria micropowder, and analyzing the particle size distribution of Poria micropowder with laser particle size distribution analyzer.
5. The method of claim 4, wherein the method of preparing ginsenoside comprises the steps of:
(1) Alkaline hydrolysis reaction
Weighing total saponins of ginseng stem and leaf, adding sodium hydroxide with the weight being 2 times that of the total saponins, adding small steel mill powder, uniformly mixing, transferring to a vacuum drying oven, setting the temperature at 170 ℃ at normal pressure, reacting for 12 hours to obtain alkaline hydrolysis reactants, standing and cooling;
(2) Silica gel mixing material
Weighing silica gel 7 times of the total amount of the materials, adding 2000ml of absolute ethyl alcohol, uniformly stirring with the alkaline hydrolysis reactant obtained in the step (1), and naturally airing or evaporating in a vacuum rotary manner;
(3) Extraction of
Adding ethyl acetate (ml) into the silica gel mixture in the step (2) according to the amount of 1:7, reflux-extracting for 1h at 80 ℃ for 2 times, and mixing to obtain a total extract;
(4) Concentrating and drying
Concentrating the extract obtained in the step (3) under reduced pressure to dryness, and drying in a vacuum drying oven to obtain the ginsenoside extract.
6. The preparation method of the tenuifolin according to claim 4, wherein the preparation method of the tenuifolin comprises the following steps:
(1) Decocting and extracting with water: weighing radix Polygalae, adding 10 times of drinking water, extracting for 3 times and 4 hr each time, mixing the water extractive solutions, and concentrating to obtain concentrated solution;
(2) Alkaline hydrolysis: adding alkali into the concentrated solution obtained in the step (1) until the concentration is 10%, and performing alkaline hydrolysis for 3 hours to obtain alkaline hydrolysis solution;
(3) Alcohol precipitation: and (3) regulating the pH value of the alkaline hydrolysis liquid obtained in the step (2) to 4-5 by using concentrated hydrochloric acid. Regulating alcohol degree to 70-90% with absolute ethyl alcohol, filtering and collecting filtrate;
(4) And (3) water sedimentation: concentrating the filtrate collected in the step (3) until no alcohol smell exists, adding 40L of drinking water for water precipitation, centrifugally collecting a precipitation part, and drying to obtain a crude tenuifolin;
(5) And (3) crystallization: reflux-recrystallizing the crude tenuifolin obtained in the step (4) with absolute ethanol to obtain tenuifolin.
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