CN111569041A

CN111569041A - Preparation method of gastrodia tuber dizziness relieving oral solid preparation

Info

Publication number: CN111569041A
Application number: CN202010591124.7A
Authority: CN
Inventors: 张贵民; 沈庆国; 关永霞; 赵昆
Original assignee: Lunan Pharmaceutical Group Corp
Current assignee: Lunan Pharmaceutical Group Corp
Priority date: 2020-06-24
Filing date: 2020-06-24
Publication date: 2020-08-25

Abstract

The invention belongs to the field of traditional Chinese medicine preparations, and particularly relates to a preparation method of a gastrodia tuber dizziness relieving oral solid preparation, which comprises the steps of firstly, extracting volatile oil from dried orange peel and ginger, and then separately decocting dregs; the effective components of the gastrodia elata are extracted by an ethanol reflux extraction method, so that the concentration operation is simple and efficient, and the loss of the effective components of the gastrodia elata caused by the fact that cutin components are adhered to the wall of the container is avoided; the gastrodia elata alcohol reflux liquid, the ginger and dried orange peel alcohol precipitation liquid, the white paeony root, the poria cocos, the liquorice and the bamboo shavings alcohol precipitation liquid are combined and concentrated, the adhesion of cutin components of the gastrodia elata extracting liquid is reduced, the production process flow is simplified, time and labor are saved, and the production efficiency is improved. The method has the advantages of simple operation, short production period and high extraction rate, ensures the stability of the preparation and improves the quality of the product.

Description

Preparation method of gastrodia tuber dizziness relieving oral solid preparation

Technical Field

The invention belongs to the field of traditional Chinese medicine preparations, and particularly relates to a preparation method of an oral solid preparation of Gastrodia elata dizziness relieving.

Background

Vertigo (Dizziness) is an illusion of movement caused by disorientation in space, is a subjective reaction of dysequilibrium in the cerebral cortex of a patient, is usually manifested by visual rotation, self-rotation, floating sensation and the like, and is a syndrome which is common in clinic and accompanied by symptoms such as nausea, vomiting, hyperhidrosis and blood pressure fluctuation. It has been reported that vertigo occurs at 0.5% in China, and its incidence is second to fever and pain. And the incidence of vertigo is increasing with the aging population and the change of living habits. The etiology and classification of vertigo are extremely complex, and are generally divided into 2 types, vestibular systemic vertigo, common etiology includes vertebrobasilar artery insufficiency, cerebral infarction, cerebral hemorrhage, brain tumor, Meniere's disease, vestibular neuronitis, benign paroxysmal positional vertigo, otitis media and the like; non-systemic vertigo is caused by hypertension, hypotension, arrhythmia, endocrine disturbance, infection, neurosis, etc.

The gastrodia tuber vertigo curing syngeneic product includes gastrodia tuber vertigo curing mixture and gastrodia tuber vertigo curing granules, and is a classic prescription for curing vertigo, and is made up by using gastrodia tuber, uncaria stem with hooks, alisma tuber, pinellia tuber, ovate atractylodes root, poria, white peony root, bamboo shavings, ligusticum root, licorice root, tangerine peel and fresh ginger, and possesses the functions of eliminating phlegm, arresting dizzy and harmonizing stomach and stopping vomiting, and can be used for curing vertigo, nausea, vomiting, pale tongue and white and smooth fur, in particular for Meniere's disease (Meniere's disease), labyrinthitis, inner ear drug poisoning, positional vertigo and motion sickness, etc. with the above-mentioned syndromes, and its therapeutic effect is definite. In the formula, the gastrodia elata and the uncaria are used for calming wind and stopping dizziness, the pinellia ternate is used for eliminating dampness and phlegm, the bighead atractylodes rhizome is used for strengthening spleen and stomach, the bamboo shavings and the rhizoma alismatis are used for clearing heat and eliminating phlegm, the poria cocos and the liquorice are used for strengthening spleen and stomach, the dried orange peel is used for regulating qi and eliminating phlegm, the ligusticum wallichii is used for activating blood and promoting qi, the white peony root is used for calming liver and relieving pain, nourishing blood and regulating menstruation, the ginger is used for preventing vomiting, eliminating phlegm and dispelling cold, so-called.

The prescription and preparation of Tianma Xuanyangning mixture are recorded in the fourteenth volume (number: WS3-B-2661-97) of the Standard Chinese medicine prescription preparation of Ministry of public health. The Chinese invention patent CN1299759C discloses a preparation method of Gastrodia elata vertigo treating granules, in the preparation process, after oil extraction of dried orange peel and ginger, medicine residues are uniformly divided and then put into a plurality of extraction tanks together with white peony root, liquorice, tuckahoe and bamboo shavings, and the uniform medicine residue feeding is difficult in actual operation, time-consuming and labor-consuming and is not suitable for industrial production in a workshop; in the existing preparation process, the gastrodia elata is decocted singly, the gastrodia elata decoction contains a large amount of cutin components, the liquid medicine becomes viscous along with the loss of water in the decoction concentration process, and particularly, the cutin components are easy to adhere to the wall of the container, so that the concentration operation is complicated, the medicine is difficult to discharge, the time consumption is long, and the loss of the effective components is large; in the preparation process, the alcohol precipitation liquid of the tangerine peel and ginger decoction, the alcohol precipitation liquid of the white paeony root, the liquorice, the tuckahoe and the bamboo shavings decoction and the alcohol precipitation liquid of the tall gastrodia tuber decoction are respectively concentrated, so that the concentration operation difficulty is increased, and the production period is long.

Disclosure of Invention

Aiming at the defects of the existing preparation process of the gastrodia tuber dizziness relieving oral solid preparation, the invention provides a novel preparation method of the gastrodia tuber dizziness relieving oral solid preparation, which leads the operation process to be simple, continuous and efficient through the improvement and the upgrade of the original preparation process, shortens the production period, improves the extraction rate of effective components, ensures the stability of the product and improves the clinical curative effect of the product.

A method for preparing oral solid preparation of Gastrodia elata for treating vertigo comprises the following steps:

A. extracting pericarpium Citri Tangerinae and rhizoma Zingiberis recens to obtain volatile oil, preparing into ethanol volatile oil solution, adding cyclodextrin, and making into cyclodextrin clathrate; filtering the distilled water solution to obtain water decoction I for later use, and decocting the residue with water for 1-2 hr to obtain water decoction II for later use; mixing the water decoction I and the water decoction II, filtering, concentrating under reduced pressure to obtain extract with relative density of 1.17-1.21 at 50-60 deg.C, adding ethanol to reach alcohol content of 40-60%, standing, and filtering to obtain alcohol solution I;

B. decocting radix Paeoniae alba, Poria, Glycyrrhrizae radix, and caulis Bambusae in Taenia in water twice, mixing water decoctions, filtering, concentrating under reduced pressure to obtain extract with relative density of 1.18-1.22 at 50-60 deg.C, adding ethanol to alcohol content of 40-60%, standing, and filtering to obtain alcohol solution II;

C. extracting rhizoma Gastrodiae with 50-70% ethanol under reflux for three times, and mixing the ethanol reflux solutions to obtain ethanol solution III; combining the alcohol solution I, the alcohol solution II and the alcohol solution III, and concentrating under reduced pressure to obtain an extract with a relative density of 1.17-1.22 at 50-60 ℃ for later use;

D. soaking ramulus Uncariae cum uncis, Alismatis rhizoma, rhizoma Ligustici Chuanxiong, rhizoma Pinelliae and Atractylodis rhizoma in 40-60% ethanol for 24-48 hr, percolating at flow rate of 3-5 ml/min until the percolate is nearly colorless, mixing the percolates, adding cyclodextrin, stirring, recovering ethanol under reduced pressure, and concentrating to obtain extract with relative density of 1.16-1.20 at 50-60 deg.C;

E. and D, combining the extract obtained in the step C and the extract obtained in the step D, adding the cyclodextrin inclusion compound obtained in the step A, uniformly stirring, drying and crushing to obtain fine powder of the gastrodia tuber dizziness extract, adding conventional auxiliary materials, and preparing the traditional Chinese medicine oral solid preparation.

Preferably, step a comprises the steps of:

extracting volatile oil from dried orange peel and ginger, and preparing the volatile oil by volume: ethanol ═ 1: 1-3, adding cyclodextrin into the ethanol volatile oil solution to prepare cyclodextrin inclusion compound for later use; filtering the distilled water solution to obtain a water decoction I for later use, and adding 8-10 times of water into the decoction dregs for decocting for 1.5 hours to obtain a water decoction II for later use; mixing the water decoction I and the water decoction II, filtering, concentrating under reduced pressure to obtain an extract with a relative density of 1.19 at 50-60 deg.C, adding ethanol to reach an alcohol content of 50%, standing, and filtering to obtain an alcohol solution I for use.

Preferably, step B comprises the steps of:

decocting radix Paeoniae alba, Poria, Glycyrrhrizae radix, and caulis Bambusae in Taenia in water twice (8-10 times the amount of the materials in the first time for 1.5-3 hr), and 6-8 times the amount of the materials in the second time for 0.5-1.5 hr, filtering, mixing filtrates, concentrating under reduced pressure to obtain extract with relative density of 1.20 at 50-60 deg.C, adding ethanol to reach ethanol content of 50%, standing, and filtering to obtain ethanol solution II.

Preferably, step C comprises the steps of:

reflux-extracting rhizoma Gastrodiae with 6 times of 60% ethanol for three times, each for 2 hr, and mixing ethanol reflux solutions to obtain ethanol solution III; and combining the alcohol solution I, the alcohol solution II and the alcohol solution III, and concentrating under reduced pressure to obtain an extract with the relative density of 1.18 at the temperature of 50-60 ℃ for later use.

Preferably, step D comprises the steps of:

soaking ramulus Uncariae cum uncis, Alismatis rhizoma, rhizoma Ligustici Chuanxiong, rhizoma Pinelliae and Atractylodis rhizoma in 50% ethanol for 24 hr, percolating at flow rate of 4.5ml/min until the percolate is nearly colorless, mixing the percolates, adding cyclodextrin, stirring, recovering ethanol under reduced pressure, and concentrating to obtain extract with relative density of 1.18 at 50-60 deg.C.

Preferably, the oral solid preparation of gastrodia elata dizziness curing is prepared from the following traditional Chinese medicine raw materials:

150 parts of gastrodia elata, 300 parts of uncaria, 600 parts of rhizoma alismatis, 600 parts of rhizoma pinelliae and 300 parts of pinellia ternata

360 parts of bighead atractylodes rhizome, 360 parts of poria cocos, 300 parts of white peony root, 300 parts of bamboo shavings

90 parts of ligusticum wallichii, 90 parts of liquorice, 180 parts of dried orange peel and 135 parts of ginger.

Further, the rhizoma gastrodiae vertigo treating oral solid pharmaceutical preparation is one of granules, capsules, tablets and microcapsules.

Another preferred dosage form of the present invention is a microencapsulated formulation, the process for the preparation of the microencapsulated formulation comprising the steps of:

1) extraction process

A. Extracting volatile oil from dried orange peel and ginger, and preparing the volatile oil by volume: ethanol ═ 1: 3, adding cyclodextrin into the ethanol volatile oil solution to prepare cyclodextrin inclusion compound for later use; filtering the distilled water solution to obtain a water decoction I for later use, adding 9 times of water into the decoction dregs, and decocting for 1.5 hours to obtain a water decoction II for later use; mixing the water decoction I and the water decoction II, filtering, concentrating under reduced pressure to obtain an extract with a relative density of 1.19 at 50-60 deg.C, adding ethanol to reach an alcohol content of 50%, standing, and filtering to obtain an alcohol solution I for use.

B. Decocting radix Paeoniae alba, Poria, Glycyrrhrizae radix, and caulis Bambusae in Taenia in water twice (10 times the amount of water for the first time and 2 hr, and 7 times the amount of water for the second time and 1 hr), filtering, mixing filtrates, concentrating under reduced pressure to obtain extract with relative density of 1.20 at 50-60 deg.C, adding ethanol to make ethanol content reach 50%, standing, and filtering to obtain ethanol solution II.

C. Extracting rhizoma Gastrodiae with 6 times of 50% ethanol under reflux twice, each for 2 hr, and mixing ethanol reflux solutions to obtain ethanol solution III; and combining the alcohol solution I, the alcohol solution II and the alcohol solution III, and concentrating under reduced pressure to obtain an extract with the relative density of 1.18 at the temperature of 50-60 ℃ for later use.

D. Soaking ramulus Uncariae cum uncis, Alismatis rhizoma, rhizoma Ligustici Chuanxiong, rhizoma Pinelliae and Atractylodis rhizoma in 50% ethanol for 24 hr, percolating at flow rate of 4.5ml/min until the percolate is nearly colorless, mixing the percolates, adding cyclodextrin, stirring, recovering ethanol under reduced pressure, and concentrating to obtain extract with relative density of 1.18 at 50-60 deg.C.

E. Mixing the extract obtained in step C and the extract obtained in step D, adding the cyclodextrin inclusion compound obtained in step A, stirring, drying, and pulverizing to obtain rhizoma Gastrodiae vertigo treating fine powder;

2) preparation process

F. Weighing the fine powder of the extract of gastrodia elata vertigo, the capsule wall material, the anti-sticking agent and the plasticizer in the step E according to the formula, adding the capsule wall material, the anti-sticking agent and the plasticizer into purified water, heating and stirring at 52 ℃ to dissolve the materials, preparing a capsule wall material solution with the mass fraction of 31.5%, cooling to room temperature, adding the fine powder of the extract of gastrodia elata vertigo and the emulsifier in a stirring state, and homogenizing and emulsifying to obtain an emulsion for later use;

G. and F, carrying out spray drying on the emulsion in the step F under the conditions that the air inlet temperature is 169 ℃, the spray pressure is 0.42MPa and the feeding speed is 22.5ml/min, collecting the microcapsules and cooling to obtain the microcapsule.

Preferably, the capsule wall material of step F is maltodextrin by weight: soy protein isolate 7: 3. the anti-tack agent is octadecanol by weight: titanium dioxide 5: 2. the plasticizer is propylene glycol by weight: citric acid ═ 3: 1.

preferably, the emulsifier in step C is soybean phospholipid by weight: the dosage of the compound emulsifier is 1.1 percent of the total amount of the preparation formula according to the mass fraction, wherein the sucrose fatty acid ester is 3: 5.

The preparation method of the oral solid preparation of gastrodia tuber dizziness relieving of the invention has the following characteristics and beneficial effects:

1) compared with the existing preparation process of the gastrodia tuber dizziness relieving preparation, the preparation method of the gastrodia tuber dizziness relieving oral solid preparation comprises the steps of adding water into pericarpium citri reticulatae and ginger decoction dregs after volatile oil extraction for decoction, combining the obtained decoction with distilled water decoction, filtering, concentrating and precipitating with ethanol, so that after oil extraction of the pericarpium citri reticulatae and the ginger, the decoction dregs are uniformly distributed and then put into a plurality of extraction tanks together with radix paeoniae alba, liquorice, poria cocos and bamboo shavings, the difficulty caused by actual operation of uniformly distributing and feeding the decoction dregs is avoided, time and labor are saved, and the gastrodia tuber dizziness relieving oral solid preparation is more suitable for industrial production in workshops;

2) compared with the single decoction and independent concentration process of gastrodia elata in the preparation of the existing gastrodia elata dizziness preparation, the gastrodia elata is extracted by ethanol reflux from the raw material of the gastrodia elata, so that a large number of cutin components are prevented from being extracted, and meanwhile, an ethanol reflux extracting solution of the gastrodia elata is combined with other two ethanol precipitation solutions for concentration, so that the phenomenon that the cutin components are adhered to the wall of a container due to water loss and liquid medicine viscosity in the concentration process of the ethanol extracting solution is avoided, the concentration operation is simple and efficient, and the loss of the medicinal components of the gastrodia elat;

3) the gastrodia elata alcohol reflux liquid, the ginger and dried orange peel alcohol precipitation liquid, the white paeony root, the poria cocos, the liquorice and the bamboo shavings alcohol precipitation liquid are combined and then concentrated together, so that the production process flow is simplified, time and labor are saved, and the production efficiency is improved;

4) the preparation process of the upgraded gastrodia tuber vertigo curing oral solid preparation is optimized, the original preparation process is improved, the operation process tends to be simple, continuous and efficient, the production period is shortened, the extraction rate of effective components is improved, the stability of the product is improved, and the clinical curative effect of the product is ensured.

Experimental example 1 selection of extraction conditions

1.1 orthogonal test factors and horizontal design

In the preparation process of the gastrodia tuber vertigo curing oral solid preparation, the effective components of the gastrodia tuber are extracted by ethanol reflux. The factors influencing the reflux extraction effect of rhizoma gastrodiae mainly include ethanol concentration, extraction times, solvent dosage and extraction time. Selecting 4 factors including alcohol concentration (A), extraction times (B), solvent dosage (C) and extraction time (D), each factor having 3 levels, taking gastrodin content as investigation index, and adopting L9 (3)⁴) Orthogonal tables are designed experimentally, and the optimal extraction process is preferred. Each cause ofThe level of the elements is designed as shown in Table 1.

TABLE 1 Gastrodia elata extraction process orthogonal test factor horizon

1.2 Gastrodin content determination

1.2.1 chromatographic Condition analytical column: sinochrom ODS-BP column, (4.6X 250mm, 5 μm); mobile phase: acetonitrile-0.05% phosphoric acid (volume ratio 3: 97); detection wavelength: 220 nm; flow rate: 1.0 ml/min; column temperature: 25 ℃; the amount of the sample was 10. mu.l.

1.2.2 preparation of reference substance solution A gastrodin reference substance of about 10mg is precisely weighed, placed in a 100ml brown measuring flask, diluted to scale with methanol, and shaken up to obtain a gastrodin reference substance solution of 100 mug/ml.

1.2.3 preparing rhizoma Gastrodiae ethanol extractive solution from the sample solution, mixing, filtering, recovering under reduced pressure, diluting to 100ml, and filtering with 0.45 μm microporous membrane.

1.2.4 preparation of Standard Curve the control solution was sampled and set up so that the autosampler would sample in volumes of 2, 4, 8 and 16. mu.L in sequence, the peak area integral was determined under the chromatographic conditions described above, the standard curve was plotted with peak area (A) as ordinate and standard control sample size (. mu.g) as abscissa, and the regression equation was found to be 4.58 × 10⁶X－5..52×10⁴(r ═ 0.9997) in the linear range 0.5-3.40. mu.g.

1.2.5 precision test 10 mul of alcohol extract of gastrodia tuber was measured precisely and repeated 6 times with RSD 0.17%.

1.2.6 repeatability tests were carried out by preparing a test solution from 6 parts of coarse powder of this product of the same lot by the method under item "1.2.3" and measuring RSD to 0.54%.

1.2.7 recovery test 9 parts of the same sample (0.358%) with known content, each part being about 5g, were precisely weighed and divided into 3 groups, each group, 3 parts, a control solution with a concentration of 1.19mg/ml was prepared according to the above-mentioned gastrodin control solution preparation method, high, medium and low gastrodin control solutions with 3 doses (5, 15ml) were precisely weighed and added to a 3000ml round-bottomed flask in which 9 parts of the sample of gastrodia elata was to be extracted, after extraction treatment according to the same extraction process, a sample solution was prepared according to the sample preparation method, 10 μ l was injected, and measurement was carried out with an average recovery of (100.3 ± 1.1)%.

1.3 analysis of orthogonal test results

TABLE 2L₉(3⁴) Results of orthogonal experiments

TABLE 3 analysis of composite score variance

Note, F_0.05(2，2)＝19，F_0.01(2，2)＝99

1.4 analysis of results

As can be seen from the visual analysis in Table 2, the optimal extraction process of the product is A₂B₃C₁D₃The influence degree of each factor on the comprehensive score is B>A>D>And C, the extraction frequency is the largest influence, the alcohol concentration is the second, the extraction time and the solvent dosage are sequentially adopted, and the extraction frequency has a remarkable influence on the extraction rate of the gastrodin.

Analysis of variance was performed on the orthogonal experiments and the results are shown in table 3. As can be seen from Table 3, the number of B-factor extractions significantly affected the extraction rate of gastrodin, while the alcohol concentration, extraction time and solvent dosage were not significantly affected. By combining actual requirements of production benefit ratio, energy conservation, consumption reduction and the like in large-scale production, the preferable extraction conditions of the gastrodia elata are as follows: extracting with 60% ethanol for 3 times, 2 hr each time, and adding 6 times of ethanol each time.

In order to verify the technical effect achieved by implementing the novel preparation method of the gastrodia tuber dizziness curing oral solid preparation, the inventor develops pharmacodynamic test research, medicament clinical research and gastrodin content comparison test research. It should be noted that the drug selected in the pharmacodynamic test and clinical study of the drug of the present invention is a drug obtained by the representative formulation and the preparation method thereof, and the tests and results related to the other formulations and the drugs obtained by the preparation method of the present invention are not exhaustive due to space limitations.

Experimental example 2 Effect on serum biochemical indices of Muslim model guinea pig with Meniere's disease membranous labyrinth hydrops

1 Material

1.1 clean-grade healthy white guinea pigs of experimental animals and feed, 60 animals, body weight (180 +/-20) g, male and female halves, agile activity and sensitive auricle reflex. All guinea pigs were provided by the lunan pharmaceutical group, inc, license number: SCXK (lu) 20180008. The method is characterized in that the animal is bred adaptively for 1 week in a clean-grade animal laboratory before experiment, male and female parts are separated, the room temperature is 20-25 ℃, the relative humidity is 40% -60%, natural illumination is carried out, and free food intake and drinking are carried out.

1.2 automatic dehydrator of instrument, reagent and medicine ZT-12P type biological tissue: the Ministry of calendaring and electronic technology in Hubei Xiaogan City; model RM2245 paraffin slicer: leica, Germany; BMJ-III type embedding machine: the Changzhou Zhongwei electronics plant; OLYMPUS CX-40 microscope: olympus, Japan; motic Images Advanced 3.2 image acquisition analysis System: miaodi group of industries, Inc.

Ethylene diamine tetraacetic acid: tianjin Yongda chemical reagent development center; paraformaldehyde: tianjin Yongda chemical reagent development center; immunohistochemistry kit MaxVision kit: fujianmei new biotechnology development Co., Ltd; AQP-2 antibody, Santa Cruz Biotechnology, Canada. Desmopressin acetate injection, shenzhen hanyu pharmaceutical industry ltd, product batch No.: 140921, approved article numbers: the national standard characters H20103133.

The test drug was a sample of granules prepared according to the formulation and method of example 3; the positive control drug is Gastrodia elata dizzy tranquilization granule (specification: 8 g/bag, batch number: 20181105), product of Lunan Kangpu pharmacy Co.

2 method

2.1 grouping and modeling 60 guinea pigs were randomly divided into 6 groups of 10 each with half male and half female groups, and divided into a normal control group, a model control group, a positive control group, a test high dose group, a test medium dose group, and a test low dose group. Except for the normal control group without any treatment, the other groups of guinea pigs are administered with desmopressin acetate by intraperitoneal injection of 4 mug/kg every day for 7 days continuously; the dose is increased to 6 mug/kg, and the intraperitoneal injection is continued for 3 days. Normal control group was given equal dose of saline for intraperitoneal injection, as with other groups. The ethology of the rats is observed every day, the spontaneous activity of the guinea pigs is reduced after the model is built, the guinea pigs are in a state of rolling, the gait is unstable, the eyeballs are normal, the eyeshocks are avoided, the auditory response is slow and other meniere disease symptoms appear, and the success of the model building is proved.

2.2 after the drug administration and the modeling are finished, the tested guinea pigs in high, medium and low dose groups are sequentially administered with 2.40g/kg, 1.20g/kg and 0.60g/kg of tested drugs for intragastric administration, which are respectively equal to 2 times, 1 time and 1/2 times of the clinical common dose of human; the positive control group is administrated with 1.20g/kg stomach irrigation (equal to the common clinical dose) of Gastrodia elata Dingxuening granules; the normal control group and the model control group are administered with 0.9% NaCl solution with the same amount for intragastric administration; each group was administered 1 time daily for 7 days.

2.3 obtaining materials, preparing specimens and HE staining, firstly, 10% chloral hydrate is injected into an abdominal cavity of a guinea pig for anesthesia, after heart perfusion, the head is quickly cut off, bilateral temporal bones are taken out, a small hole is cut on the back of an auricular vesicle to the cochlear surface, and the specimens are placed in a 4% paraformaldehyde refrigerator at 4 ℃ for 48 hours for fixation. And (3) placing the fixed cochlear specimen in 10% ethylenediaminetetraacetic acid decalcifying solution for decalcifying, and decalcifying for 5 hours at 20-30 ℃ in combination with 30% of microwave quantity. Then, the tissues are washed by flowing water, dehydrated by alcohol step by step, transparent by xylene, embedded by paraffin, sliced, the slicing direction is parallel to the cochlear modium, the thickness of each slice is 3 mu m, 1 slice is taken every other 3 slices, and HE staining is carried out.

2.4 index detection

2.4.1 Observation of the behavioral changes of each group of animals: the spontaneous activity of guinea pigs, whether gait is stable, whether eyeball rotation is flexible, and whether auditory response is quick.

2.4.2 Using the dynamic Images Advanced 3.2 image acquisition and analysis system, the ratio of the sum of the cross-sectional area of the cochlear duct and the cross-sectional area of the cochlear duct plus the vestibular order of each guinea pig in each group and the average value of each group were calculated.

2.5 evaluation and data statistical analysis method of membrane labyrinth hydrops

2.5.1 evaluation of Membrane labyrinth hydrops under normal conditions, the included angle between the cochlear vestibular membrane and the basilar membrane is about 30 degrees, and the vestibular membrane divides the space above the basilar membrane into a vestibular scala and a cochlear duct. The cross-sectional area of the scroll was about 1/3 of the space above the basement membrane. When the membrane is subjected to labyrinth hydrops, the vestibular membrane expands towards the scala vestibuli, and the cross-sectional area of the cochlear duct is increased. Under an optical microscope, the degree of membrane labyrinth hydrops is divided into light degree, medium degree and heavy degree, and the degree is slight: the area of the worm pipe is 1/3-1/2 of the total area; medium: the area of the worm pipe is 1/2-2/3 of the total area; and (3) severe degree: the scroll area is greater than about total area 2/3.

2.5.2 statistical treatment SPSS19.0 statistical software was used for analysis, and the experimental data were expressed as "mean. + -. standard deviation

"is expressed in terms of form. The comparison among groups was performed by one-way anova, with P <0.05 indicating that the difference was statistically significant.

3 results

3.1 general behavioral observations that the guinea pigs in the normal control group have normal spontaneous activity, steady gait, normal eyeball rotation and sensitive hearing. Most guinea pigs in the model control group had reduced spontaneous activity, a contracture state, unstable gait, normal eyeball rotation, no eye shake, and slow auditory response. Part of guinea pigs in the positive control group have normal spontaneous activity, stable gait, normal eyeball rotation and quick auditory response; some guinea pigs have reduced spontaneous activity, are in a compressed state, have unstable gait, normal eyeball rotation, no tremor and slow auditory response. Some guinea pigs in the high-dose group tested exhibited reduced spontaneous activity, unstable gait, and sluggish auditory response; part of guinea pigs move normally spontaneously, gait is stable, eyeball rotation is normal, and auditory response is quick. In the test, most guinea pigs in the dosage group have normal spontaneous activity, stable gait, normal eyeball rotation and quick auditory response; the spontaneous activity of a small part of guinea pigs is reduced, the gait is stable, and the eyeball and auditory reaction are normal. Most guinea pigs in the low dose group tested exhibited reduced spontaneous activity, a rolling state, unstable gait, and impaired auditory response.

3.2 histological test results in the temporal bone section of the control guinea pig, the vestibular membrane is flat and has no bulge, no structural abnormality is caused in the vestibular scala, scala tympani and cochlear duct, and no guinea pig has membranous labyrinth hydrops.

The model control group has different degrees of membranous labyrinth hydrops, which is characterized in that the vestibular membrane expands to the vestibular order to different degrees, and part of the vestibular membrane is fractured. Of these, 9(9/10) guinea pigs developed membranous labyrinth hydroncus, 3 of which were mildly hydroncus, 4 of which were moderately hydroncus, and 2 of which were severely hydroncus.

After treatment, in the temporal bone section of the positive control guinea pigs, part of the vestibular membranes of the guinea pigs slightly expand to the scala vestibuli, no structural abnormality exists in the scala vestibuli, the scala tympani and the cochlear duct, and 4(4/10) guinea pigs have membranous labyrinth hydrops which are all slight hydrops.

In the temporalis slice of a high-dose guinea pig, the vestibular membrane expands to the scala vestibuli to different degrees, and the scala vestibuli, scala tympani and cochlear duct have no structural abnormality; in 2(2/10) of the guinea pigs, mild edema was observed. In the temporal bone slice of the guinea pigs in the dose group in the test, most of the guinea pigs had a straight vestibular membrane without swelling, and a part slightly swelled towards the vestibular order; there were 4(4/10) water accumulations, of which 1 had moderate accumulation and the rest had mild accumulation. In the test low-dose group temporal bone slices, the vestibular membranes of most guinea pigs swell to the vestibular order to different degrees, and 6(6/10) guinea pigs have membranous labyrinth hydrops, wherein 1 is heavily hydropsy, 1 is moderately hydropsy, and the rest is lightly hydropsy. The incidence of membranous labyrinth hydrops in each group of guinea pigs is shown in table 4.

TABLE 4 incidence of membranal labyrinth hydrops in guinea pigs of each group

3.3 comparison of the ratio of the area of each group of cochlear ducts to the total area shows by statistical analysis that: compared with the normal control group, the ratio of the area of the cochlear duct to the total area of the model group is relatively higher, and the significant difference is shown (P < 0.05). After 7d of administration, compared with a model control group, the ratio of the areas of the worm canals of the high, medium and low dose groups of the reagent and the positive control group to the total area is relatively low and has significant difference (P is less than 0.05), and compared with the positive control group, the ratio of the areas of the worm canals of the high dose group of the reagent and the total area is relatively low and has significant difference (P is less than 0.05), which indicates that the effect of the novel preparation is better than that of the Gastrodia elata dizzy ning granules of the positive control group when the novel preparation is applied according to the high dose level. Compared with the positive control group, the ratio of the area of the cochlear duct to the total area of the reagent low-dose group has no significant difference (P > 0.05). The results are shown in Table 5.

TABLE 5 ratio of cochlear duct area to total area of guinea pig groups

Note: comparison with normal control group: p <0.05 for "_▲"means; comparison with model control group: p <0.05 is denoted by "+"; p <0.05 for positive control group "_◇"means.

Experimental example 3 Gastrodin content comparative test study

In order to verify the effect of the technical scheme of the invention on improving the content of the main effective component gastrodin extracted from gastrodia elata, on the premise that the dosage of raw medicinal materials and the used equipment are the same, the inventor prepares the gastrodin granule according to the novel preparation method of the gastrodin granule and the Chinese patent CN1299759C of the invention, and selectively determines and compares the content of gastrodin in the liquid medicine according to the method for determining the content of the gastrodin 1.2 in the experimental example 1. The gastrodine content of both methods is shown in table 7.

TABLE 7 Gastrodin content comparison test of different Gastrodia elata vertigo treating granule preparation methods

The test results in table 7 show that, under the condition that other conditions are parallel and consistent, the gastrodine content of the invention and the gastrodine content of the prior art are respectively 0.0365mg/ml and 0.0302mg/ml, and compared with the prior art, the gastrodine content of the invention is improved by 17.26%.

Detailed Description

The present invention is further illustrated by the following specific examples, which are not intended to limit the invention in any way, as will be appreciated by those skilled in the art.

Example 1 preparation of Gastrodia Capsule for vertigo

A. Extracting volatile oil from dried orange peel and ginger, and preparing the volatile oil by volume: ethanol ═ 1: 1, adding cyclodextrin into ethanol volatile oil solution to be encapsulated into cyclodextrin inclusion compound for later use; filtering the distilled water solution to obtain a water decoction I for later use, and adding 9 times of water into the decoction dregs for decocting for 2 hours to obtain a water decoction II for later use; mixing the water decoction I and the water decoction II, filtering, concentrating under reduced pressure to obtain an extract with a relative density of 1.20 at 50-60 ℃, adding ethanol to reach an alcohol content of 60%, standing, and filtering to obtain an alcohol solution I for later use.

B. Decocting radix Paeoniae alba, Poria, Glycyrrhrizae radix, and caulis Bambusae in Taenia in water twice (9 times the amount of water for the first time and 2 hr), adding 7 times the amount of water for the second time, decocting for 0.5 hr, filtering, mixing filtrates, concentrating under reduced pressure to obtain extract with relative density of 1.21 at 50-60 deg.C, adding ethanol to make ethanol content reach 60%, standing, and filtering to obtain ethanol solution II.

C. Extracting rhizoma Gastrodiae with 5 times of 70% ethanol under reflux for three times, each for 2 hr, and mixing ethanol reflux solutions to obtain ethanol solution III; and combining the alcohol solution I, the alcohol solution II and the alcohol solution III, and concentrating under reduced pressure to obtain an extract with the relative density of 1.20 at the temperature of 50-60 ℃ for later use.

D. Soaking ramulus Uncariae cum uncis, Alismatis rhizoma, rhizoma Ligustici Chuanxiong, rhizoma Pinelliae and Atractylodis rhizoma in 50% ethanol for 36 hr, percolating at flow rate of 5ml/min until the percolate is nearly colorless, mixing the percolates, adding cyclodextrin, stirring, recovering ethanol under reduced pressure, and concentrating to obtain extract with relative density of 1.19 at 50-60 deg.C.

E. And D, mixing the extract obtained in the step C and the extract obtained in the step D, adding the cyclodextrin inclusion compound obtained in the step A, uniformly stirring, drying, crushing to obtain fine powder of the gastrodia elata dizzy tannin extract, adding the starch and the superfine silica gel powder (the weight ratio is 3: 1) according to the formula amount, uniformly mixing, granulating, drying, grading, filling, polishing in a polishing machine, and removing damaged capsules to obtain the gastrodia elata dizzy tannin capsule.

Example 2 preparation of Gastrodia elata tablet for treating vertigo

A. Extracting volatile oil from dried orange peel and ginger, and preparing the volatile oil by volume: ethanol ═ 1: 3, adding cyclodextrin into the ethanol volatile oil solution to prepare cyclodextrin inclusion compound for later use; filtering the distilled water solution to obtain a water decoction I for later use, and adding 8 times of water into the decoction dregs for decocting for 1 hour to obtain a water decoction II for later use; mixing the water decoction I and the water decoction II, filtering, concentrating under reduced pressure to obtain an extract with a relative density of 1.18 at 50-60 ℃, adding ethanol to reach an alcohol content of 50%, standing, and filtering to obtain an alcohol solution I for later use.

B. Decocting radix Paeoniae alba, Poria, Glycyrrhrizae radix, and caulis Bambusae in Taenia in water twice (8 times the amount of water for the first time and 1.5 hr for the second time and 6 times the amount of water for the second time) for 1.0 hr, filtering, mixing filtrates, concentrating under reduced pressure to obtain extract with relative density of 1.19 at 50-60 deg.C, adding ethanol to make ethanol content 40%, standing, and filtering to obtain ethanol solution II.

C. Extracting rhizoma Gastrodiae with 7 times of 50% ethanol under reflux for three times, each for 2 hr, and mixing ethanol reflux solutions to obtain ethanol solution III; and combining the alcohol solution I, the alcohol solution II and the alcohol solution III, and concentrating under reduced pressure to obtain an extract with the relative density of 1.22 at the temperature of 50-60 ℃ for later use.

D. Soaking ramulus Uncariae cum uncis, Alismatis rhizoma, rhizoma Ligustici Chuanxiong, rhizoma Pinelliae and Atractylodis rhizoma in 40% ethanol for 48 hr, percolating at flow rate of 4ml/min until the percolate is nearly colorless, mixing the percolates, adding cyclodextrin, stirring, recovering ethanol under reduced pressure, and concentrating to obtain extract with relative density of 1.18 at 50-60 deg.C.

E. And D, combining the extract obtained in the step C and the extract obtained in the step D, adding the cyclodextrin inclusion compound obtained in the step A, stirring uniformly, drying, crushing to obtain rhizoma gastrodiae dizzy ning extract fine powder, adding microcrystalline cellulose and sodium carboxymethyl starch (the weight ratio is 5: 3) according to the formula amount, mixing uniformly, preparing into coarse particles, drying, crushing, sieving, granulating, drying at low temperature, finishing particles, adding 0.4% of magnesium stearate and 0.15% of talcum powder, mixing uniformly, pressing into 10000 tablets, and coating a film coat to obtain the traditional Chinese medicine composition.

Example 3 preparation of Gastrodia elata vertigo treating granule

A. Extracting volatile oil from dried orange peel and ginger, and preparing the volatile oil by volume: ethanol ═ 1: 2, adding cyclodextrin into the ethanol volatile oil solution to prepare cyclodextrin inclusion compound for later use; filtering the distilled water solution to obtain a water decoction I for later use, and adding 10 times of water into the decoction dregs for decocting for 1.5 hours to obtain a water decoction II for later use; mixing the water decoction I and the water decoction II, filtering, concentrating under reduced pressure to obtain an extract with a relative density of 1.19 at 50-60 deg.C, adding ethanol to reach an alcohol content of 50%, standing, and filtering to obtain an alcohol solution I for use.

B. Decocting radix Paeoniae alba, Poria, Glycyrrhrizae radix, and caulis Bambusae in Taenia in water twice (10 times the amount of water for the first time and 3 hr for the second time and 8 times the amount of water for 1 hr for the second time), filtering, mixing filtrates, concentrating under reduced pressure to obtain extract with relative density of 1.20 at 50-60 deg.C, adding ethanol to make ethanol content reach 50%, standing, and filtering to obtain ethanol solution II.

C. Reflux-extracting rhizoma Gastrodiae with 6 times of 60% ethanol for three times, each for 2 hr, and mixing ethanol reflux solutions to obtain ethanol solution III; and combining the alcohol solution I, the alcohol solution II and the alcohol solution III, and concentrating under reduced pressure to obtain an extract with the relative density of 1.18 at the temperature of 50-60 ℃ for later use.

E. And D, combining the extract obtained in the step C and the extract obtained in the step D, adding the cyclodextrin inclusion compound obtained in the step A, uniformly stirring, drying and crushing to obtain fine powder of the gastrodia elata dizzy tannin extract, adding the sucrose powder, the hydroxypropyl starch and the mannitol (in a weight ratio of 5: 2: 2) according to the formula, uniformly mixing, granulating, drying, finishing granules and preparing into 10 kg.

Example 4 preparation of Gastrodia elata tablet for vertigo

A. Extracting volatile oil from dried orange peel and ginger, and preparing the volatile oil by volume: ethanol ═ 1: 2, adding cyclodextrin into the ethanol volatile oil solution to prepare cyclodextrin inclusion compound for later use; filtering the distilled water solution to obtain a water decoction I for later use, and adding 8 times of water into the decoction dregs for decocting for 1.5 hours to obtain a water decoction II for later use; mixing the water decoction I and the water decoction II, filtering, concentrating under reduced pressure to obtain an extract with a relative density of 1.17 at 50-60 ℃, adding ethanol to make the alcohol content reach 40%, standing, and filtering to obtain an alcohol solution I for later use.

B. Decocting radix Paeoniae alba, Poria, Glycyrrhrizae radix, and caulis Bambusae in Taenia in water twice (10 times the amount of water for the first time and 2.5 hr each time), adding 6 times the amount of water for the second time, decocting for 1.5 hr each time, filtering, mixing filtrates, concentrating under reduced pressure to obtain extract with relative density of 1.22 at 50-60 deg.C, adding ethanol to make ethanol content 40%, standing, and filtering to obtain ethanol solution II.

C. Extracting rhizoma Gastrodiae with 5 times of 50% ethanol under reflux for three times, each for 2 hr, and mixing ethanol reflux solutions to obtain ethanol solution III; and combining the alcohol solution I, the alcohol solution II and the alcohol solution III, and concentrating under reduced pressure to obtain an extract with the relative density of 1.19 at the temperature of 50-60 ℃ for later use.

D. Soaking ramulus Uncariae cum uncis, Alismatis rhizoma, rhizoma Ligustici Chuanxiong, rhizoma Pinelliae and Atractylodis rhizoma in 60% ethanol for 48 hr, percolating at flow rate of 3.5ml/min until the percolate is nearly colorless, mixing the percolates, adding cyclodextrin, stirring, recovering ethanol under reduced pressure, and concentrating to obtain extract with relative density of 1.20 at 50-60 deg.C.

E. And D, combining the extract obtained in the step C and the extract obtained in the step D, adding the cyclodextrin inclusion compound obtained in the step A, stirring uniformly, drying, crushing to obtain rhizoma gastrodiae dizzy ning extract fine powder, adding the starch, the dextrin and the sucrose (the weight ratio is 3: 2: 1) according to the formula amount, mixing uniformly, preparing into coarse particles, drying, crushing, sieving, granulating, drying at low temperature, finishing particles, adding 0.6% of magnesium stearate, mixing uniformly, pressing into 10000 tablets, and coating a film to obtain the traditional Chinese medicine composition.

Example 5 preparation of Gastrodia Capsule for vertigo

A. Extracting volatile oil from dried orange peel and ginger, and preparing the volatile oil by volume: ethanol ═ 1: 1, adding cyclodextrin into ethanol volatile oil solution to be encapsulated into cyclodextrin inclusion compound for later use; filtering the distilled water solution to obtain a water decoction I for later use, and adding 9 times of water into the decoction dregs for decocting for 2 hours to obtain a water decoction II for later use; mixing the water decoction I and the water decoction II, filtering, concentrating under reduced pressure to obtain an extract with a relative density of 1.18 at 50-60 ℃, adding ethanol to reach an alcohol content of 50%, standing, and filtering to obtain an alcohol solution I for later use.

B. Decocting radix Paeoniae alba, Poria, Glycyrrhrizae radix, and caulis Bambusae in Taenia in water twice (9 times the amount of water for the first time and 3 hr), adding 7 times the amount of water for the second time, decocting for 0.5 hr, filtering, mixing filtrates, concentrating under reduced pressure to obtain extract with relative density of 1.18 at 50-60 deg.C, adding ethanol to make ethanol content reach 60%, standing, and filtering to obtain ethanol solution II.

C. Extracting rhizoma Gastrodiae with 7 times of 70% ethanol under reflux for three times, each for 2 hr, and mixing ethanol reflux solutions to obtain ethanol solution III; and combining the alcohol solution I, the alcohol solution II and the alcohol solution III, and concentrating under reduced pressure to obtain an extract with the relative density of 1.17 at the temperature of 50-60 ℃ for later use.

D. Soaking ramulus Uncariae cum uncis, Alismatis rhizoma, rhizoma Ligustici Chuanxiong, rhizoma Pinelliae and Atractylodis rhizoma in 50% ethanol for 36 hr, percolating at flow rate of 3ml/min until the percolate is nearly colorless, mixing the percolates, adding cyclodextrin, stirring, recovering ethanol under reduced pressure, and concentrating to obtain extract with relative density of 1.16 at 50-60 deg.C.

E. And D, combining the extract obtained in the step C and the extract obtained in the step D, adding the cyclodextrin inclusion compound obtained in the step A, uniformly stirring, drying and crushing to obtain fine powder of the gastrodia elata dizzy quiet extract, adding the starch, the silica gel micropowder and the low-substituted hydroxypropyl cellulose (the weight ratio is 2: 1: 1) in the formula amount, uniformly mixing, granulating, drying, grading, filling, polishing in a polishing machine, and removing damaged capsules to obtain the gastrodia elata dizzy tranquilizer.

Example 6 preparation of Gastrodia elata vertigo treating granule

A. Extracting volatile oil from dried orange peel and ginger, and preparing the volatile oil by volume: ethanol ═ 1: 2, adding cyclodextrin into the ethanol volatile oil solution to prepare cyclodextrin inclusion compound for later use; filtering the distilled water solution to obtain a water decoction I for later use, and adding 10 times of water into the decoction dregs for decocting for 1 hour to obtain a water decoction II for later use; mixing the water decoction I and the water decoction II, filtering, concentrating under reduced pressure to obtain an extract with a relative density of 1.19 at 50-60 ℃, adding ethanol to reach an alcohol content of 60%, standing, and filtering to obtain an alcohol solution I for later use.

B. Decocting radix Paeoniae alba, Poria, Glycyrrhrizae radix, and caulis Bambusae in Taenia in water twice (8 times the amount of water for the first time and 2 hr), adding 8 times the amount of water for the second time, decocting for 1.5 hr, filtering, mixing filtrates, concentrating under reduced pressure to obtain extract with relative density of 1.20 at 50-60 deg.C, adding ethanol to make ethanol content reach 50%, standing, and filtering to obtain ethanol solution II.

C. Reflux-extracting rhizoma Gastrodiae with 6 times of 60% ethanol for three times, each for 2 hr, and mixing ethanol reflux solutions to obtain ethanol solution III; and combining the alcohol solution I, the alcohol solution II and the alcohol solution III, and concentrating under reduced pressure to obtain an extract with the relative density of 1.22 at the temperature of 50-60 ℃ for later use.

D. Soaking ramulus Uncariae cum uncis, Alismatis rhizoma, rhizoma Ligustici Chuanxiong, rhizoma Pinelliae and Atractylodis rhizoma in 40% ethanol for 36 hr, percolating at flow rate of 5ml/min until the percolate is nearly colorless, mixing the percolates, adding cyclodextrin, stirring, recovering ethanol under reduced pressure, and concentrating to obtain extract with relative density of 1.17 at 50-60 deg.C.

E. And D, combining the extract obtained in the step C and the extract obtained in the step D, adding the cyclodextrin inclusion compound obtained in the step A, uniformly stirring, drying, crushing to obtain fine powder of the gastrodia elata dizzy tannin extract, adding the sucrose powder and the dextrin (the weight ratio is 3: 1) according to the formula amount, uniformly mixing, granulating, drying, and finishing to obtain 10kg of the gastrodia elata dizzy tannin extract.

Example 7 preparation of Gastrodia elata Dihuangning micro-capsules for treating vertigo

1) Extraction process

2) preparation process

F. Weighing 5.6kg of maltodextrin, 2.4kg of soybean protein isolate, 0.1kg of octadecanol, 0.04kg of titanium dioxide, 0.15kg of propylene glycol and 0.05kg of citric acid according to the formula ratio, adding purified water, heating and stirring at 52 ℃ to dissolve, preparing a capsule material solution with the mass fraction of 31.5%, cooling to room temperature, adding 0.041kg of rhizoma gastrodiae dizzy ning extract fine powder, 0.069kg of soybean lecithin and 0.069kg of sucrose fatty acid ester under the stirring state, homogenizing and emulsifying to obtain an emulsion for later use;

E. and F, carrying out spray drying on the emulsion in the step F under the conditions that the air inlet temperature is 169 ℃, the spray pressure is 0.42MPa and the feeding speed is 22.5ml/min, collecting the microcapsules and cooling to obtain the microcapsule.

Example 8 preparation of Gastrodia elata tablet for vertigo

A. Extracting volatile oil from dried orange peel and ginger, and preparing the volatile oil by volume: ethanol ═ 1: 2, adding cyclodextrin into the ethanol volatile oil solution to prepare cyclodextrin inclusion compound for later use; filtering the distilled water solution to obtain a water decoction I for later use, and adding 10 times of water into the decoction dregs for decocting for 1 hour to obtain a water decoction II for later use; mixing the water decoction I and the water decoction II, filtering, concentrating under reduced pressure to obtain an extract with a relative density of 1.20 at 50-60 ℃, adding ethanol to reach an alcohol content of 50%, standing, and filtering to obtain an alcohol solution I for later use.

B. Decocting radix Paeoniae alba, Poria, Glycyrrhrizae radix, and caulis Bambusae in Taenia in water twice (9 times the amount of water for the first time and 2 hr), adding 6 times the amount of water for the second time, decocting for 1 hr, filtering, mixing filtrates, concentrating under reduced pressure to obtain extract with relative density of 1.21 at 50-60 deg.C, adding ethanol to make ethanol content reach 50%, standing, and filtering to obtain ethanol solution II.

C. Reflux-extracting rhizoma Gastrodiae with 7 times of 60% ethanol for three times, each for 2 hr, and mixing ethanol reflux solutions to obtain ethanol solution III; and combining the alcohol solution I, the alcohol solution II and the alcohol solution III, and concentrating under reduced pressure to obtain an extract with the relative density of 1.18 at the temperature of 50-60 ℃ for later use.

D. Soaking ramulus Uncariae cum uncis, Alismatis rhizoma, rhizoma Ligustici Chuanxiong, rhizoma Pinelliae and Atractylodis rhizoma in 40% ethanol for 48 hr, percolating at flow rate of 3ml/min until the percolate is nearly colorless, mixing the percolates, adding cyclodextrin, stirring, recovering ethanol under reduced pressure, and concentrating to obtain extract with relative density of 1.18 at 50-60 deg.C.

E. And D, combining the extract obtained in the step C and the extract obtained in the step D, adding the cyclodextrin inclusion compound obtained in the step A, uniformly stirring, drying, crushing to obtain fine powder of the gastrodia elata dizzy tannin extract, adding the microcrystalline fiber and the hydroxypropyl fiber (the weight ratio is 7: 3) according to the formula amount, uniformly mixing, preparing coarse granules, drying, crushing, sieving, preparing granules, drying at low temperature, finishing granules, adding 0.5% of magnesium stearate, uniformly mixing, pressing into 10000 tablets, and coating a film coat to obtain the gastrodia elata dizzy tannin tablet.

Example 9 preparation of Gastrodia elata vertigo treating granule

B. Decocting radix Paeoniae alba, Poria, Glycyrrhrizae radix, and caulis Bambusae in Taenia in water twice (9 times the amount of water for the first time and 3 hr), adding 8 times the amount of water for the second time, decocting for 1.5 hr, filtering, mixing filtrates, concentrating under reduced pressure to obtain extract with relative density of 1.20 at 50-60 deg.C, adding ethanol to make ethanol content reach 60%, standing, and filtering to obtain ethanol solution II.

C. Extracting rhizoma Gastrodiae with 6 times of 50% ethanol under reflux for three times, each for 2 hr, and mixing ethanol reflux solutions to obtain ethanol solution III; and combining the alcohol solution I, the alcohol solution II and the alcohol solution III, and concentrating under reduced pressure to obtain an extract with the relative density of 1.17 at the temperature of 50-60 ℃ for later use.

D. Soaking ramulus Uncariae cum uncis, Alismatis rhizoma, rhizoma Ligustici Chuanxiong, rhizoma Pinelliae and Atractylodis rhizoma in 50% ethanol for 36 hr, percolating at flow rate of 3.5ml/min until the percolate is nearly colorless, mixing the percolates, adding cyclodextrin, stirring, recovering ethanol under reduced pressure, and concentrating to obtain extract with relative density of 1.19 at 50-60 deg.C.

E. And D, combining the extract obtained in the step C and the extract obtained in the step D, adding the cyclodextrin inclusion compound obtained in the step A, uniformly stirring, drying and crushing to obtain fine powder of the gastrodia elata dizzy tannin extract, adding the sucrose powder, the hydroxypropyl starch and the mannitol (in a weight ratio of 4: 3: 1) according to the formula, uniformly mixing, granulating, drying, finishing granules and preparing into 10 kg.

Example 10 preparation of Gastrodia elata vertigo capsule

A. Extracting volatile oil from dried orange peel and ginger, and preparing the volatile oil by volume: ethanol ═ 1: 1, adding cyclodextrin into ethanol volatile oil solution to be encapsulated into cyclodextrin inclusion compound for later use; filtering the distilled water solution to obtain a water decoction I for later use, and adding 10 times of water into the decoction dregs for decocting for 1.5 hours to obtain a water decoction II for later use; mixing the water decoction I and the water decoction II, filtering, concentrating under reduced pressure to obtain an extract with a relative density of 1.19 at 50-60 ℃, adding ethanol to reach an alcohol content of 60%, standing, and filtering to obtain an alcohol solution I for later use.

B. Decocting radix Paeoniae alba, Poria, Glycyrrhrizae radix, and caulis Bambusae in Taenia in water twice (8 times the amount of water for the first time and 1.5 hr for the second time and 7 times the amount of water for the second time), filtering, mixing filtrates, concentrating under reduced pressure to obtain extract with relative density of 1.19 at 50-60 deg.C, adding ethanol to reach ethanol content of 50%, standing, and filtering to obtain ethanol solution II.

C. Extracting rhizoma Gastrodiae with 5 times of 70% ethanol under reflux for three times, each for 2 hr, and mixing ethanol reflux solutions to obtain ethanol solution III; and combining the alcohol solution I, the alcohol solution II and the alcohol solution III, and concentrating under reduced pressure to obtain an extract with the relative density of 1.2 at the temperature of 50-60 ℃ for later use.

D. Soaking ramulus Uncariae cum uncis, Alismatis rhizoma, rhizoma Ligustici Chuanxiong, rhizoma Pinelliae and Atractylodis rhizoma in 60% ethanol for 24 hr, percolating at flow rate of 4.5ml/min until the percolate is nearly colorless, mixing the percolates, adding cyclodextrin, stirring, recovering ethanol under reduced pressure, and concentrating to obtain extract with relative density of 1.16 at 50-60 deg.C.

E. And D, mixing the extract obtained in the step C and the extract obtained in the step D, adding the cyclodextrin inclusion compound obtained in the step A, uniformly stirring, drying, crushing to obtain fine powder of the gastrodia elata dizzy tannin extract, adding the starch and the microcrystalline cellulose (the weight ratio is 7: 3) according to the formula amount, uniformly mixing, granulating, drying, grading, filling, polishing in a polishing machine, and removing damaged capsules to obtain the gastrodia elata dizzy tannin capsule.

Claims

1. A preparation method of an oral solid preparation of Gastrodia elata for treating dizziness is characterized by comprising the following steps:

2. The method of claim 1, wherein step a comprises the steps of:

3. The method of claim 1, wherein step B comprises the steps of:

4. The method of claim 1, wherein step C comprises the steps of:

5. The method of claim 1, wherein step D comprises the steps of:

6. The method of manufacturing according to claims 1-5, wherein the oral solid pharmaceutical formulation is one of granules, capsules, tablets and microcapsules.

7. The preparation method of claim 6, wherein the oral solid preparation for treating vertigo of gastrodia elata is prepared from the following traditional Chinese medicine raw materials:

8. the method for preparing the microcapsule according to claim 7, comprising the steps of:

1) extraction process

2) preparation process

9. The method of claim 8, wherein step F the capsule wall material comprises maltodextrin by weight: soy protein isolate 7: 3. the anti-tack agent is octadecanol by weight: titanium dioxide 5: 2. the plasticizer is propylene glycol by weight: citric acid ═ 3: 1.

10. the method of claim 8, wherein step C said emulsifier is a soy phospholipid by weight: the dosage of the compound emulsifier is 1.1 percent of the total amount of the preparation formula according to the mass fraction, wherein the sucrose fatty acid ester is 3: 5.