CN114748599A - Pinellia ternate, bighead atractylodes rhizome and gastrodia elata particle composition as well as preparation and application thereof - Google Patents

Pinellia ternate, bighead atractylodes rhizome and gastrodia elata particle composition as well as preparation and application thereof Download PDF

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CN114748599A
CN114748599A CN202210431191.1A CN202210431191A CN114748599A CN 114748599 A CN114748599 A CN 114748599A CN 202210431191 A CN202210431191 A CN 202210431191A CN 114748599 A CN114748599 A CN 114748599A
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atractylodes rhizome
bighead atractylodes
gastrodia elata
pinellia ternate
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王淑玲
杨菲菲
孙云廷
徐男
李欣岳
叶珂珂
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Hangzhou Normal University
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Hangzhou Normal University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/888Araceae (Arum family), e.g. caladium, calla lily or skunk cabbage
    • A61K36/8888Pinellia
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Abstract

The invention discloses a granule composition of pinellia ternate, bighead atractylodes rhizome and gastrodia elata as well as preparation and application thereof. Is prepared from plant water extract and medicinal adjuvants, and is prepared from rhizoma Pinelliae Preparada, rhizoma Gastrodiae, Poria, exocarpium Citri rubrum, Atractylodis rhizoma, Glycyrrhrizae radix, rhizoma Zingiberis recens, and fructus Jujubae by granulating with high-speed stirring granulator. The pinellia ternate, bighead atractylodes rhizome and gastrodia elata particles not only keep the effects of eliminating dampness and phlegm and calming the liver to stop the wind of the original prescription, but also overcome the defects of temporary decoction, time and energy consumption, easy mildew and rancidity after long-term storage and the like, and also enable the dosage of the particles to be smaller and the particles to be more convenient to take, carry, store and transport. The pinellia ternate, bighead atractylodes rhizome and gastrodia elata granules reduce the labor intensity to a large extent, shorten the labor time, greatly reduce the burden of people, fill up the market vacancy, have considerable economic benefits and have obvious advantages.

Description

Pinellia ternate, bighead atractylodes rhizome and gastrodia elata particle composition as well as preparation and application thereof
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a granular composition containing pinellia ternate, bighead atractylodes rhizome and gastrodia elata as well as preparation and application of the granular composition.
Background
Hypertension is a significant public health problem worldwide. It is estimated that 13.9 million people worldwide have hypertension in 2010. The prevalence rate of hypertension in China is high, and the treatment management rate is low. The incidence of hypertension has increased significantly in our country over the past few decades, particularly in rural areas. Obesity, age and lifestyle are common risk factors for hypertension. Hypertension is also a major, independent risk factor for cardiovascular disease, and clinical trials have shown that lowering blood pressure can reduce cardiovascular disease and premature death. Many pharmaceutical formulations have been approved for the treatment of hypertension, but many have potential side effects, or are only used in individual patients. Moreover, hypertension has many complications and is difficult to treat. Hypertension can cause problems such as heart failure, stroke, vision problems, kidney disease, etc.
The composition has effects of eliminating dampness and phlegm, calming liver and calming endogenous wind. It is mainly used for treating dizziness, headache, chest distress, nausea, vomiting, white and greasy tongue coating, wiry and slippery pulse and other symptoms caused by wind-phlegm upward disturbance. The prescription is a common prescription for treating the syndrome of wind-phlegm, and is still widely used in the traditional Chinese medicine clinical application in modern times, such as the treatment of hypertension phlegm-dampness accumulation type, phlegm-dampness type inner ear vertigo syndrome (Meniere's syndrome), epilepsy caused by phlegm-induced heart resuscitation, apoplexy and sequelae caused by wind-phlegm obstruction of channels and collaterals, and the like. The wind-phlegm syndrome is caused by the spleen dampness generating phlegm, phlegm obstructing the clear yang, and the stirring of liver wind and wind-phlegm disturbing the head. The former people have the saying that the liver is the same as the former people who have no phlegm and do not feel dizzy and the former people who have all wind and dizzy. Stirring of liver wind can cause dizziness, which is aggravated by up-disturbance of damp-phlegm and up-reversal of turbid yin, resulting in vomiting and nausea. For phlegm-resolving and wind-extinguishing, it is indicated. In the recipe, ban Xia is pungent and warm in property, so it is good at drying dampness and resolving phlegm, checking adverse rise of qi and checking vomiting to treat its root; gastrodia elata, sweet and neutral in nature, is good at calming liver, stopping wind and stopping dizziness, so it is indicated for its symptoms. The two medicines are combined to take the root and the symptoms into consideration, and the special effect of resolving phlegm and stopping endogenous wind is taken as the monarch medicine. The bighead atractylodes rhizome is used as a minister, has the effects of strengthening spleen and eliminating dampness, and is combined with the pinellia tuber and the tall gastrodia tuber to achieve the good effects of eliminating dampness and phlegm and stopping dizziness. Poria cocos, rhizoma Atractylodis Macrocephalae, and rhizoma Atractylodis Macrocephalae, by compatibility with rhizoma Atractylodis Macrocephalae, is especially suitable for treating phlegm generation; juhong regulates qi to resolve phlegm, and regulates qi to resolve phlegm. The liquorice is used for regulating the functions of the traditional Chinese medicine and the traditional Chinese medicine, and the traditional Chinese medicine are used together to play the effects of reducing phlegm and calming endogenous wind. Wind-extinguishing phlegm-eliminating, vertigo and self-healing.
The pinellia ternate, bighead atractylodes rhizome and gastrodia elata particles have the advantages of being fast to absorb, fast in effect, strong in effect and the like, meanwhile, the defects that decoction is temporarily decocted, time and energy are consumed, and the decoction is easy to mildew and decay after being placed for a long time are overcome, the dosage is smaller, and the pinellia ternate, bighead atractylodes rhizome and gastrodia elata particles are convenient to take, carry, store and transport. The pinellia ternate, bighead atractylodes rhizome and gastrodia elata granules reduce the labor intensity to a large extent, fill the vacancy in the market, have considerable economic benefit and have obvious advantages.
Disclosure of Invention
The invention aims to solve the problems in the prior art and provides a granular composition of pinellia tuber, white atractylodes rhizome and tall gastrodia tuber, which provides theoretical support for the subsequent enlarged production of the granules of the pinellia tuber, white atractylodes rhizome and tall gastrodia tuber.
The invention is realized by the following technical scheme:
the pinellia ternate, bighead atractylodes rhizome and gastrodia elata particle composition comprises a plant water extract and a pharmaceutic adjuvant, wherein the plant water extract is prepared from the following components in parts by weight: 5-10 parts of prepared pinellia ternate, 5-10 parts of gastrodia elata, 5-10 parts of poria cocos, 5-15 parts of exocarpium citri rubrum, 10-20 parts of bighead atractylodes rhizome, 1-5 parts of liquorice, 1-5 parts of ginger and 1-5 parts of Chinese date;
the pharmaceutic adjuvant comprises a filling agent, a wetting agent and an adhesive; the filler is one or more of sucrose, starch, dextrin, lactose, mannitol and sodium alginate; the wetting agent is 80-95% ethanol (volume content) or water; wherein the filler accounts for 30 to 60 percent of the weight of the pinellia ternate, bighead atractylodes rhizome and gastrodia elata particle composition; the wetting agent accounts for 5 to 15 percent of the weight of the pinellia ternate, bighead atractylodes rhizome and gastrodia elata particle composition; the adhesive accounts for 0 to 5 percent of the weight of the pinellia ternate, bighead atractylodes rhizome and gastrodia elata particle composition;
Preferably, the adhesive is one of povidone, polyethylene glycol and hydroxypropyl cellulose;
preferably, the plant water extract comprises the following components in percentage by weight: 10 parts of prepared pinellia tuber, 5 parts of tall gastrodia tuber, 5 parts of Indian buead, 5 parts of red tangerine peel, 10 parts of largehead atractylodes rhizome, 3 parts of liquoric root, 2 parts of ginger and 1 part of Chinese date.
The invention also aims to provide a preparation method of the pinellia ternate, bighead atractylodes rhizome and gastrodia elata particle composition, which comprises the following steps:
1) weighing pinellia ternate, gastrodia elata, poria cocos, exocarpium citri rubrum, bighead atractylodes rhizome, liquorice, ginger and Chinese dates according to the formula amount, respectively crushing and mixing to obtain a medicinal material mixture;
2) adding 1.0-2.0% of an enzyme reagent I (m/m) into the medicinal material mixture prepared in the step 1), and pretreating for 12-24 hours;
3) adding 10, 8 and 8 times of water by mass into the pretreated medicinal materials in the step 2), respectively adjusting the pH to 1-6, 6-9 and 6-9, respectively adding 0.1-1.0% of enzyme reagent II (m/m) and 0.1-1.0% of enzyme reagent III (m/m) into the first extraction and the third extraction, respectively, leaching for three times at 37-60 ℃ for 0.5-1 hour each time, filtering and combining filtrate, and concentrating to 1/3-2/3 of the original dosage to obtain water extraction concentrated solution;
4) Adding ethanol into the water extraction concentrated solution until the ethanol concentration is 60-80% (v/v), placing for 24h at 4 ℃ in a refrigerator, uniformly mixing, centrifuging, taking supernate, concentrating to 1/3-2/3 of the original dosage, drying under reduced pressure, and pulverizing to obtain dry extract powder;
5) opening a high-speed stirring granulator, setting parameters, adding dry extract powder and a filler into a mixing tank, opening a stirring paddle for dry mixing, uniformly adding an adhesive and a wetting agent in the wet mixing process, opening a cutting knife, discharging after granulation is finished, and drying at the constant temperature of 70 ℃ for 30-60 min;
6) packaging;
the enzyme reagent I is one or more of cellulase, hemicellulase and pectinase, the enzyme reagent II is one or more of pepsin, trypsin and papain, and the enzyme reagent III is one or more of pepsin, trypsin and papain;
preferably, the parameters of the high-speed stirring granulator in the step 4) are as follows: the dry mixing time is 3-5 min, the wet mixing time is 5-15 min, the granulation time is 1-4 min, the dry mixing stirring speed is 400-600 rpm, the wet mixing stirring speed is 400-600 rpm, the granulation stirring speed is 1000-1500 rpm, and the cutting speed is 2000-3000 rpm.
The third purpose of the invention is to provide the application of the pinellia ternate, bighead atractylodes rhizome and tall gastrodia tuber granular composition in preparing the medicines for treating or improving phlegm-dampness stagnation type Meniere's syndrome.
The fourth purpose of the invention is to provide a medicine for treating or improving phlegm-damp stagnation type auditory vertigo, which comprises a pinellia ternate, bighead atractylodes rhizome and gastrodia elata particle composition.
The invention has the advantages that:
the quality inspection and pharmacodynamic experiments prove that the prepared pinellia ternate, bighead atractylodes rhizome and gastrodia elata particles are safe and effective, on the basis of fully considering practicability and effectiveness and previous research, the pinellia ternate, bighead atractylodes rhizome and gastrodia elata particles not only keep the effects of a raw medicine formula of eliminating dampness and phlegm and calming the liver and calming the wind, but also overcome the defects of temporary decoction, time consumption and energy consumption, easiness in mildew and deterioration after long-term placement and the like, and are smaller in dosage and more convenient to take, carry, store and transport. The pinellia ternate, bighead atractylodes rhizome and gastrodia elata granules reduce the labor intensity to a large extent, shorten the labor time, greatly reduce the burden of people, fill up the market vacancy, have considerable economic benefits and have obvious advantages.
Drawings
FIG. 1: pinellia ternate, bighead atractylodes rhizome and gastrodia elata granules.
Detailed Description
As described above, in view of the deficiencies of the prior art, the present inventors have long studied and extensively practiced to provide the technical solutions of the present invention, which are mainly based on at least: 1) in the recipe, ban Xia is pungent and warm in nature, and good at moistening phlegm, checking adverse rise of qi and checking vomiting to treat its root; tian Ma is sweet and neutral in nature and good at pacifying liver and stopping wind and dizziness. The two medicines are used together, the principal and secondary aspects are considered, and the special efficacy of reducing phlegm and stopping endogenous wind is taken as the monarch medicine. The atractylodes macrocephala koidz is used as the minister and is used for strengthening the spleen and eliminating dampness, and the atractylodes macrocephala koidz is used together with the pinellia tuber and the gastrodia tuber to achieve the good effects of eliminating dampness and reducing phlegm and relieving dizziness. Poria cocos, rhizoma Atractylodis Macrocephalae, and rhizoma Atractylodis Macrocephalae, by compatibility with rhizoma Atractylodis Macrocephalae, is especially suitable for treating phlegm generation; tangerine peel, fructus Citri Tangerinae and fructus Citri Tangerinae Red have the effects of regulating qi-flowing for eliminating phlegm, and guiding qi downward to eliminate phlegm. The liquorice is used for regulating the functions of the traditional Chinese medicine and the traditional Chinese medicine, and the traditional Chinese medicine are used together to play the effects of reducing phlegm and calming endogenous wind. Wind-extinguishing phlegm-eliminating, vertigo and self-healing. Is especially effective in treating or improving phlegm-damp obstruction type Meniere's syndrome. 2) The invention combines the mixing and granulating processes by using a high-speed stirring granulator, thereby saving time, meeting GMP requirements, reducing cross contamination and greatly improving efficiency. 3) The pinellia ternate, bighead atractylodes rhizome and gastrodia elata granules not only keep the effects of eliminating dampness and phlegm and calming the liver to stop the wind of the original prescription, but also overcome the defects of temporary decoction, time and energy consumption, easy mildewing and rancidity after long-term storage and the like, reduce the dosage, and are more convenient to take, carry, store and transport.
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and do not limit the invention. In addition, the technical features involved in the respective embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
In a first aspect, a preparation method of a pinellia ternate, bighead atractylodes rhizome and gastrodia elata particle composition comprises the following steps:
1) respectively weighing 5-10 parts by weight of pinellia ternate, 5-10 parts by weight of gastrodia elata, 5-10 parts by weight of poria cocos, 5-15 parts by weight of exocarpium citri rubrum, 10-20 parts by weight of bighead atractylodes rhizome, 1-5 parts by weight of liquorice, 1-5 parts by weight of ginger and 1-5 parts by weight of Chinese date, respectively crushing and mixing to obtain a medicinal material mixture;
2) adding 1.0-2.0% of an enzyme reagent I into the medicinal material mixture prepared in the step 1), and pretreating for 12-24 hours; the enzyme reagent I is one or more of cellulase, hemicellulase and pectinase;
3) adding 10, 8 and 8 times of water by mass into the pretreated medicinal materials in the step 2), respectively adjusting the pH to 1-6, 6-9 and 6-9, respectively adding 0.1-1.0% of enzyme reagent II and 0.1-1.0% of enzyme reagent III into the first extraction and the third extraction, respectively, leaching for three times at 37-60 ℃ for 0.5-1 h each time, filtering and combining the filtrates, and concentrating to 1/3-2/3 of the original dosage to obtain a water extraction concentrated solution; the enzyme reagent II is one or more of pepsin, trypsin and papain, and the enzyme reagent III is one or more of pepsin, trypsin and papain.
4) Adding ethanol into the water-extracted concentrated solution until the ethanol concentration is 60-80%, placing for 24h at 4 ℃ in a refrigerator, uniformly mixing, centrifuging, taking supernatant, concentrating to 1/3-2/3 of the original drug amount, drying under reduced pressure, and crushing to obtain dry paste powder;
5) opening a high-speed stirring granulator, setting parameters, adding dry paste powder and a filler into a mixing tank, opening a stirring paddle for dry mixing, uniformly adding an adhesive and a wetting agent in the wet mixing process, opening a cutting knife, discharging after granulation is finished, and drying at the constant temperature of 70 ℃ for 30-60 min; the filler is one or more of sucrose, starch, dextrin, lactose, mannitol and sodium alginate, and accounts for 30-60 wt% of the particulate composition of rhizoma pinelliae, rhizoma atractylodis macrocephalae and rhizoma gastrodiae; the adhesive accounts for 0 to 5 percent of the weight of the pinellia ternate, bighead atractylodes rhizome and gastrodia elata particle composition;
6) and (6) packaging.
Preferably, the wetting agent is 80-95% ethanol or water.
Preferably, the wetting agent accounts for 5-15% of the weight of the pinellia ternate, bighead atractylodes rhizome and gastrodia elata particle composition.
Preferably, the binder is one of povidone, polyethylene glycol and hydroxypropyl cellulose.
Preferably, the parameters of the high-speed stirring granulator in the step 5) are as follows: the dry mixing time is 3-5 min, the wet mixing time is 5-15 min, the granulation time is 1-4 min, the dry mixing stirring speed is 400-600 rpm, the wet mixing stirring speed is 400-600 rpm, the granulation stirring speed is 1000-1500 rpm, and the cutting speed is 2000-3000 rpm.
In a second aspect, the pinellia ternate, bighead atractylodes rhizome and gastrodia elata particle composition is prepared by the method and comprises plant water extracts and medicinal auxiliary materials; wherein the plant water extract is a water extract prepared from the following components in parts by weight: 5-10 parts of prepared pinellia tuber, 5-10 parts of gastrodia tuber, 5-10 parts of poria cocos, 5-15 parts of red tangerine peel, 10-20 parts of bighead atractylodes rhizome, 1-5 parts of liquorice, 1-5 parts of ginger and 1-5 parts of Chinese date, wherein the medicinal auxiliary materials comprise a filling agent, a wetting agent and a binding agent.
In a third aspect, the application of the pinellia ternate, bighead atractylodes rhizome and gastrodia elata particle composition in preparing the medicine for treating or improving phlegm-damp stagnation type auditory vertigo is provided.
The technical solutions of the present invention are further explained below with reference to some preferred embodiments, but the experimental conditions and the setting parameters should not be construed as limitations of the basic technical solutions of the present invention. And the scope of the present invention is not limited to the following examples.
Example 1
Weighing 10g of pinellia ternate, 5g of rhizoma gastrodiae, 5g of poria cocos, 5g of exocarpium citri rubrum, 10g of rhizoma atractylodis macrocephalae, 3g of liquorice, 2g of ginger and 1g of Chinese date respectively, crushing and mixing to obtain a medicinal material mixture. Adding 1.5% enzyme reagent I (cellulase) into the medicinal material mixture, and pretreating for 24 h. Adding 10, 8 and 8 times of water respectively, adjusting pH to 5, 7 and 8, adding 1.0% enzyme reagent II (pepsin) and 0.5% enzyme reagent III (trypsin) into the first extract and the third extract respectively, leaching at 50 deg.C for three times, each time for 1h, filtering, mixing filtrates, and concentrating to 1/3 of original dosage to obtain water extract concentrate. Adding ethanol into the concentrated water extract until the ethanol concentration is 60%, standing at 4 deg.C for 24 hr, mixing, centrifuging, collecting supernatant, concentrating to 2/5 of original dosage, drying under reduced pressure, and pulverizing to obtain dry extract powder. Opening a high-speed stirring granulator, setting parameters (dry mixing time is 4min, wet mixing time is 8min, granulating time is 4min, dry mixing stirring speed is 400rpm, wet mixing stirring speed is 500rpm, granulating stirring speed is 1500rpm, and cutting speed is 2000rpm), adding 2kg of dry extract powder and 1kg of filler (starch: mannitol is 3: 2) into a mixing tank, opening a stirring paddle for dry mixing, uniformly adding 0.3kg of povidone ethanol solution (the mass ratio of povidone to 90% ethanol is 5: 95) in the wet mixing process, opening a cutting knife, discharging after granulating, and drying at constant temperature of 70 ℃ for 60 min.
The brain-invigorating granules prepared in example 1 were subjected to index detection according to the appearance and examination items of particle size, moisture content and solubility of the granules in the 2020 version of Chinese pharmacopoeia, and the results are shown in Table 1 and the final product diagram is shown in FIG. 1.
TABLE 1 test results
Figure BDA0003610641060000061
Example 2
The extraction method (SBEE), the alcohol extraction method (AE) and the water extraction method (WE) are respectively optimized to prepare 3 extracting solutions. Comprehensive evaluation is carried out by taking gastrodin (HPLC method), glycyrrhetinic acid (HPLC method), an extract with the molecular weight less than or equal to 1000Da (constant weight method), HPLC integral total area, total polysaccharide (ultraviolet spectrophotometry method) and dry extract yield (constant weight method) as indexes, SBEE liquid, WE liquid and AE liquid are compared, and a better extraction method is preliminarily judged. The results are shown in tables 2 to 7.
TABLE 2 determination of gastrodin content
Figure BDA0003610641060000062
TABLE 3 measurement results of glycyrrhetinic acid content
Figure BDA0003610641060000063
TABLE 4 determination of the molecular weight ≤ 1000Da extract
Figure BDA0003610641060000071
TABLE 5HPLC INTEGRATED Total area measurement results
Figure BDA0003610641060000072
TABLE 6 determination of Total polysaccharides
Figure BDA0003610641060000073
TABLE 7 determination of Dry extract yield
Figure BDA0003610641060000074
The index data are normalized by the following formulas (I), (II), and the normalized X'i.jAnd summing after weighting the values to obtain a comprehensive evaluation index Y value (the result is shown in a table 8).
Figure RE-GDA0003642899620000075
Figure RE-GDA0003642899620000076
In the formula, Xi.jIs the content of the component j in the sample liquid i,
Figure BDA0003610641060000077
Is the average value of the component j in the sample liquid i, SjIs the standard deviation, X 'of component j'i.jAre normalized values.
TABLE 8 contents of index components and normalized results
Figure BDA0003610641060000078
Figure BDA0003610641060000081
Note: the mass of the Chinese medicinal materials in the formula is equivalent to the mass of the Chinese medicinal materials in the formula;
the number in brackets is the value after the standardization treatment;
and (c) Y ═ Y (gastrodin + glycyrrhetinic acid + extract with molecular weight less than or equal to 1000)/3 × 7+ (polysaccharide + HPLC total peak area)/2 × 2+ dry extract × 1.
The comprehensive evaluation value of the result is from big to smallThe sequence is as follows: y isSBEE>YWE>YAEThe SBEE extraction method is preferred for the preliminary explanation.
Example 3
Taking 40 SD rats, putting general feed and a certain amount of kaolin feed into cages to feed animals, adaptively feeding for two weeks, randomly dividing into 5 groups in the third week, wherein each group comprises 8 animals, namely a normal control group, a blank control group, a high dose group, a medium dose group and a low dose group. The normal control group and the blank control group are filled with plain boiled water for 1 time, and rats in the administration group are respectively filled with pinellia ternate, bighead atractylodes rhizome and gastrodia elata particle aqueous solution for 2g/kg (low dose group), 4g/kg (medium dose group) and 8g/kg (high dose group). After 0.5h, except the normal control group, 4 groups of rats are placed in a low-speed centrifuge to centrifuge at 250rpm for 5min, then the rats are taken out, and the operations are repeated after 2min until the accumulated time of the rats in the centrifuge is 20 min. Then, the intake of kaolin in 3 days was observed in 5 groups of rats. The experimental results were averaged. The rats were tested for significance of mean between groups and compared between groups (t-test) with the results shown in table 9. The average value of the amount of kaolin eaten by the rats for three days is processed to obtain R 1' as an evaluation value.
50 mice, half of each of which was female and male, were divided into 5 groups, which were a normal control group, a blank control group, a high dose group, a medium dose group, and a low dose group. The normal control group and the blank control group are filled with plain boiled water, and the other groups of mice are respectively filled with the pinellia ternate, bighead atractylodes rhizome and gastrodia elata particle aqueous solution for intragastric administration for 2g/kg (low dose group), 4g/kg (medium dose group) and 8g/kg (high dose group). After 0.5h, the other 4 groups of mice except the normal control group are placed in a low-speed centrifuge to be centrifuged at 250rpm for 5min, the mice are immediately placed on a horizontal rod with the length of 60cm and the diameter of 0.8cm, and the shortest time from the end of centrifugation to the time when the mice stand stably on the rod and can walk on the rod smoothly is recorded. The experimental results were averaged. Comparison between groups (t-test). After the experiment, the mouse hair is erected, shakes throughout the body, does reverse-time needle annular motion, is unstable when standing on a horizontal rod with the length of 60cm and the diameter of 0.8cm, and falls down freely; then, the stick can be held, the body sags but can not fall down, the hair is upright, and the symptoms of shaking all over the body still exist; finally, it can stand stably and freely walk on the rod without hair and verticalAnd the symptoms of shaking the whole body. The experimental results were subjected to an inter-group mean significance test and an inter-group comparison (t-test). The shortest time results for each group of mice to stand steady on the rod after the spin experiment are shown in table 10. The average value of the shortest time for the mouse to stand stably on the rod is processed to obtain R 2' as a rating value.
R is to be1′、R2' according to the relationship: rB=(R1′+R2')/2. To obtain RBThe value is more preferable as an evaluation index of the influence on the phlegm-dampness middle-blocking type auditory vertigo mice. The results are shown in Table 11.
TABLE 9 comparison of amounts of Kaolin (g) eaten by rats in each group for three days after the spin experiment
Figure BDA0003610641060000091
Figure BDA0003610641060000092
Note that comparing (i) with the blank control,P﹤0.001,▼P﹤0.01,p > 0.05; compared with the normal control group,
#P﹤0.001。
Figure BDA0003610641060000093
Figure BDA0003610641060000094
the average value of the amount of the kaolin eaten by the rats in the blank group,
Figure BDA0003610641060000095
the average amount of kaolin eaten by the rats in each group was calculated.
Table 10 the minimum time for each group of mice to stand on the rod after the spin experiment (min,
Figure BDA0003610641060000096
)
Figure BDA0003610641060000097
note: t "+" indicates that the animal died.
② compared with the blank control group,P﹤0.001,p < 0.01; compared with the normal control group,#P﹤0.001。
Figure BDA0003610641060000098
Figure BDA0003610641060000099
is the minimum time average value of the blank group of mice standing stably on the rod,
Figure BDA00036106410600000910
the mean of the minimum time for each group of mice to stand steady on the rod.
TABLE 11 comprehensive assessment R of various groups of animals after the spin experimentBValue of
Figure BDA0003610641060000101
Note: rB=(R1′+R2′)/2
Results of rat rotation excitability experiments show that compared with a blank control group, the eating amount of kaolin of rats in each group is reduced, wherein the eating amount of kaolin of high-dose groups and medium-dose groups is obviously reduced, the eating amount of kaolin of low-dose groups is not obvious, and no significant difference (P & gt 0.05) exists, so that the rhizoma pinelliae and rhizoma gastrodiae granules with high and medium doses have stronger effect of resisting rat rotation excitability vertigo.
The results of the mouse rotation stimulation experiments show that the mice in each group are remarkably reduced in the shortest time of standing on the rod compared with a blank control group, and the statistical significance is achieved. R is2The sequence of the values is that the high dose group is more than the middle dose group is more than the low dose group, which shows that the pinellia tuber and gastrodia elata granules have stronger effect of resisting the mouse rotation-induced vertigo.
In a mouse rotation stimulation test, the results of each experimental group are obviously different from those of a normal group, the animals die in a blank group, the condition that the physical stimulation of the animal dizziness caused by rotation molding is too strong, the rotation time, the rotation speed and other conditions need to be further optimized, the animals of other experimental groups do not die, and the effect of the pinellia ternate, bighead atractylodes rhizome and gastrodia elata particles on resisting mouse experimental phlegm-damp middle-obstruction type auditory vertigo is strong.
Finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art will understand that various changes, modifications and substitutions can be made without departing from the spirit and scope of the present invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (10)

1. The preparation method of the pinellia ternate, bighead atractylodes rhizome and gastrodia elata particle composition is characterized by comprising the following steps of:
1) weighing 5-10 parts by weight of pinellia ternate, 5-10 parts by weight of gastrodia elata, 5-10 parts by weight of poria cocos, 5-15 parts by weight of exocarpium citri rubrum, 10-20 parts by weight of bighead atractylodes rhizome, 1-5 parts by weight of liquorice, 1-5 parts by weight of ginger and 1-5 parts by weight of Chinese date, respectively crushing and mixing to obtain a medicinal material mixture;
2) adding 1.0-2.0% of an enzyme reagent I into the medicinal material mixture prepared in the step 1), and pretreating for 12-24 hours; the enzyme reagent I is one or more of cellulase, hemicellulase and pectinase;
3) adding 10, 8 and 8 times of water by mass into the pretreated medicinal materials in the step 2), respectively adjusting the pH to 1-6, 6-9 and 6-9, respectively adding 0.1-1.0% of enzyme reagent II and 0.1-1.0% of enzyme reagent III into the first extraction and the third extraction, respectively, leaching for three times at 37-60 ℃ for 0.5-1 h each time, filtering and combining the filtrates, and concentrating to 1/3-2/3 of the original dosage to obtain a water extraction concentrated solution; the enzyme reagent II is one or more of pepsin, trypsin and papain, and the enzyme reagent III is one or more of pepsin, trypsin and papain.
4) Adding ethanol into the water extraction concentrated solution until the ethanol concentration is 60-80%, placing for 24h at 4 ℃ in a refrigerator, uniformly mixing, centrifuging, taking supernate, concentrating to 1/3-2/3 of the original dosage, drying under reduced pressure, and crushing to obtain dry extract powder;
5) opening a high-speed stirring granulator, setting parameters, adding dry extract powder and a filler into a mixing tank, opening a stirring paddle for dry mixing, uniformly adding an adhesive and a wetting agent in the wet mixing process, opening a cutting knife, discharging after granulation is finished, and drying at the constant temperature of 70 ℃ for 30-60 min; the filler is one or more of sucrose, starch, dextrin, lactose, mannitol and sodium alginate, and accounts for 30-60 wt% of the pinellia ternate, bighead atractylodes rhizome and gastrodia elata particle composition; the adhesive accounts for 0 to 5 percent of the weight of the pinellia ternate, bighead atractylodes rhizome and gastrodia elata particle composition;
6) and (6) packaging.
2. The method for preparing a granule composition, comprising pinellia ternate, bighead atractylodes rhizome and gastrodia elata as claimed in claim 1, wherein the wetting agent is 80% -95% ethanol or water.
3. The method for preparing the granule composition of ban Xia Bai Zhu Tian Mao as claimed in claim 1 or 2, wherein the wetting agent is 5-15% by weight of the granule composition of ban Xia Bai Zhu Tian Ma.
4. The method for preparing a granule composition, as claimed in claim 1, wherein the binder is one of povidone, polyethylene glycol, and hydroxypropyl cellulose.
5. The method for preparing a granule composition of ban Xia Bai Zhu Tian in claim 1, wherein the parameters of the high speed stirring granulator in step 5) are: the dry mixing time is 3-5 min, the wet mixing time is 5-15 min, the granulating time is 1-4 min, the dry mixing stirring speed is 400-600 rpm, the wet mixing stirring speed is 400-600 rpm, the granulating stirring speed is 1000-1500 rpm, and the cutting speed is 2000-3000 rpm.
6. The preparation method of the granule composition containing pinellia ternate, bighead atractylodes rhizome and gastrodia elata as claimed in claim 1, wherein the dosage of each component in step 1) is as follows: 10 parts of prepared pinellia tuber, 5 parts of tall gastrodia tuber, 5 parts of Indian buead, 5 parts of red tangerine peel, 10 parts of largehead atractylodes rhizome, 3 parts of liquoric root, 2 parts of ginger and 1 part of Chinese date.
7. A particulate composition of pinellia ternate, atractylodes macrocephala koidz and gastrodia elata is prepared by the method of any one of claims 1-6, and is characterized by comprising a plant water extract and a pharmaceutical excipient; wherein the plant water extract is a water extract prepared from the following components in parts by weight: 5-10 parts of prepared pinellia tuber, 5-10 parts of gastrodia tuber, 5-10 parts of poria cocos, 5-15 parts of red tangerine peel, 10-20 parts of bighead atractylodes rhizome, 1-5 parts of liquorice, 1-5 parts of ginger and 1-5 parts of Chinese date, wherein the medicinal auxiliary materials comprise a filling agent, a wetting agent and a binding agent.
8. The granule composition of pinellia ternate, bighead atractylodes rhizome and gastrodia elata as claimed in claim 7, wherein the aqueous extract of the plant is a water extract of the following components in parts by weight: 10 parts of prepared pinellia tuber, 5 parts of gastrodia tuber, 5 parts of tuckahoe, 5 parts of red tangerine peel, 10 parts of atractylodes macrocephala, 3 parts of liquorice, 2 parts of ginger and 1 part of Chinese date.
9. The use of the granule composition of ban Xia Bai Zhu Tian, as claimed in claim 7 or 8, in the preparation of a medicament for treating or improving phlegm-damp stagnation type Meniere's syndrome.
10. A medicine for treating or improving phlegm-damp stagnation type Meniere's disease, which is characterized by comprising the pinellia ternate, largehead atractylodes rhizome and tall gastrodia tuber granular composition as claimed in claim 7 or 8.
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