CN1332690C - Technique for preparing Yueju capsule and quality control method - Google Patents
Technique for preparing Yueju capsule and quality control method Download PDFInfo
- Publication number
- CN1332690C CN1332690C CNB2004100701262A CN200410070126A CN1332690C CN 1332690 C CN1332690 C CN 1332690C CN B2004100701262 A CNB2004100701262 A CN B2004100701262A CN 200410070126 A CN200410070126 A CN 200410070126A CN 1332690 C CN1332690 C CN 1332690C
- Authority
- CN
- China
- Prior art keywords
- solution
- adds
- medicinal material
- control medicinal
- capsule
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention discloses a preparation technology, a quality control method and a new purpose thereof for capsules of yueju compositions. After decoction pieces are put into crude drugs to be wetted by water, volatile oil is extracted, and filter residues are decocted by adding 8 to 12 times of water. Water extraction filter liquors are concentrated and added with alcohol to stir, rest, filter, concentrate, dry and crumble. The volatile oil is packed by caraway, the alcohol is used for palletizing, lubricants are added to manufacture capsules, and the capsules of yueju compositions are obtained. The present invention also discloses a method for identifying contents of capsule preparations for Yueju compositions and for measuring contents of cape jasmine glycosides, and simultaneously discloses an application for the yueju compositions to prepare medicines for treating depression and liver depression.
Description
Technical field
The present invention relates to a kind of preparation technology, method of quality control and new purposes of capsule of pharmaceutical composition of Chinese medicine, particularly relate to a kind of preparation technology, method of quality control and new purposes of bringing up the capsule of compositions more.
Background technology
Yueju Wan records in P598 of Pharmacopoeia of the People's Republic of China version in 2000.This side is the water pill agent, former technology be " the above five tastes are pulverized and are fine powder, sieve, and mixing is used water pill, drying, promptly " usage and consumption are " oral, a 6～9g, 2 times on the one ", function cure mainly for: " resolving depression of regulating the flow of vital energy, the chest stuffiness relieving removes full.It is vexed to be used for breast gastral cavity painful abdominal mass, distension in the abdomen, retention of food and drink, belch acid regurgitation." water pill is a kind of common dosage form of Chinese medicine, brought into play very big effect in the past, but its drawback is also fairly obvious.The water pill taking dose is big, the control of microorganisms difficulty, and poor stability is the common fault of this dosage form.For this prescription, water pill has following deficiency: 1. this prescription most drug contains volatile ingredient, and water pill is unfavorable to the preservation of this element of the first species.2. the dose of should writing out a prescription is bigger, is 18g crude drug/day to the maximum, and for patients with depression, the dose conference brings treatment to go up the difficulty of doctor from property.3. Massa Medicata Fermentata is made by multi-flavor medicine and flour and Testa Tritici fermentation in the prescription, directly be used as medicine, in storage and transportation microorganism wayward, especially mycete does not meet the requirement of modern Chinese medicine.4. writing out a prescription, former to be used for the treatment of breast gastral cavity painful abdominal mass vexed, distension in the abdomen, retention of food and drink, the belch acid regurgitation, therefore the existing indication of intending increasing the treatment depression extracts refining to prescription, it is necessary to remove crudely and store essence, and for promoting what is beneficial and abolish what is harmful, intends being developed to capsule on the basis of water pill now.
Summary of the invention
The object of the present invention is to provide the preparation technology who brings up composition capsule more to reach the method for quality control of bringing up compositions more.The present invention seeks to be achieved through the following technical solutions:
Rhizoma Cyperi (processed with vinegar), Fructus Gardeniae (parched), Rhizoma Atractylodis (parched), Rhizoma Chuanxiong, the stir-fry Massa Medicata Fermentata five tastes medicine of getting equivalent feed intake with decoction pieces, adding 3～4 times of water gagings soaked into after 1 hour, add 8～10 times of water gagings and extracted volatile oil 6～8 hours, filtering residue adds 8～12 times of water gagings and decocts 1-3 time, each 1-3 hour.Water extract filtrate is concentrated into relative density is 1.15 ± 0.02 under 60 ℃ of conditions, adds the 70-90% ethanol of 4～10 times of extractum amounts, fully stir, left standstill 8-24 hour, filter, filtering residue discards, and reclaims ethanol, concentrate, 40～50 ℃ of drying under reduced pressure of thick paste, pulverize extract powder.Volatile oil beta-cyclodextrin inclusion compound, the rate of charge of volatile oil and beta-schardinger dextrin-are 1: 8-12, and 40～60 ℃ of following insulated and stirred, mixing speed are 400～1200rpm, mixing time is 1～3 hour.Extract powder adds beta-schardinger dextrin-and starch by 2: 1: 1～3, the alcohol granulation with 90%, 50 ℃ of dryings, be 1.5-2.5 hour drying time, the selection consumption be 1.5% micropowder silica gel as lubricant, the Capsules of packing into is made capsule, promptly.
The method of quality control of bringing up compositions more comprises to be differentiated and/or assay.
Discrimination method comprises a kind of and/or several in the following method:
A. get and bring up composite preparation capsule 's content 2g more, porphyrize adds methanol 15～30ml supersound process 20～40 minutes, filters, and filtrate is concentrated into dried, adds methanol 1ml and makes dissolving, as need testing solution.Other gets Fructus Gardeniae control medicinal material 1g, shines medical material solution in pairs with legal system; Draw need testing solution and each 10ul of control medicinal material solution, put respectively on same silica gel g thin-layer plate, with 4～6: 2.5～3.5: the ethyl acetate-acetone of 1: 1 ratio-formic acid-water is developing solvent, launches, takes out, dries; Spray is with 5～15% ethanol solution of sulfuric acid, and hot blast blows to speckle and develops the color; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
B. get and bring up composite preparation capsule 's content 3g more, porphyrize, the 20～40ml that adds diethyl ether, reflux 1-1.5 hour, put coldly, filter, filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, as need testing solution; Other gets Rhizoma Atractylodis control medicinal material 1g, shines medical material solution in pairs with legal system; Drawing need testing solution and each 10ul of control medicinal material solution solution, put respectively on same silica gel g thin-layer plate, is developing solvent with 60～90 ℃ of petroleum ether, launch, take out, dry, spray is with the 8-12% ethanol solution of sulfuric acid of 4～6% paradime thylaminobenzaldehydes, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the speckle of same color.
C. get and bring up composite preparation capsule 's content 4g more, porphyrize adds ethyl acetate 10～20ml, and supersound process 15～30 minutes filters, and filtrate is concentrated into 1ml as need testing solution; Rhizoma Chuanxiong control medicinal material 1g shines medical material solution in pairs with legal system in addition; Draw need testing solution and each 10ul of control medicinal material solution solution, put respectively on same silica gel g thin-layer plate, with 8～10: the normal hexane-ethyl acetate of 1 ratio is developing solvent, launches, and takes out, and dries; Put under the 365nm uviol lamp and inspect; In the test sample chromatograph, showing the fluorescence speckle of same color with the corresponding position of reference substance chromatograph.
D. get and bring up composite preparation capsule 's content 3g more, porphyrize, the 15～30ml that adds diethyl ether, supersound process 15～30 minutes filters, and filtrate simmer down to 1ml is as need testing solution; Other gets Rhizoma Cyperi control medicinal material 1g, shines medical material solution in pairs with legal system; Drawing need testing solution and each 10ul of control medicinal material solution solution and put respectively on same silica gel g thin-layer plate, is developing solvent with the ethyl acetate-petroleum ether of 1: 5～6 ratios, launches, and takes out, and dries; Spray is with 4～6% phosphomolybdic acid-alcoholic solution, and 105～110 ℃ to be heated to the speckle colour developing clear; In the test sample chromatograph, with the control medicinal material chromatograph in corresponding position, show the speckle of same color.
The content assaying method of jasminoidin among the present invention:
Chromatographic condition: with octadecylsilane chemically bonded silica is filler; 10～20: 80～90 acetonitrile-waters are mobile phase; Flow velocity: 1.0mlmin
-1Detect wavelength: 238nm; Column temperature: 35 ℃; The external standard method peak area quantification.
Reference substance solution preparation: take by weighing at 3～5 hours jasminoidin reference substance of 60 ℃ of drying under reduced pressure, add methanol and make solution that every 1ml contains 30ug promptly.
The need testing solution preparation: the extract powder 0.1g of the compositions of getting it filled, it is fixed to claim after the constant weight, puts in the 25ml volumetric flask to add methanol to scale, supersound process 20～40 minutes, put coldly, supply volume, shake up with methanol, filter, precision is measured subsequent filtrate 5ml, puts in the 10ml volumetric flask, adds methanol to scale, shake up, promptly.
Algoscopy: draw each 10ul of reference substance solution and need testing solution respectively, inject chromatograph of liquid, measure, promptly.
Every of capsule of the present invention contains the jasminoidin meter must not be less than 4.50～6.00mg;
Content assaying method: in methanol can substitute by 70% ethanol or ethyl acetate; Ultrasonic processing method wherein can be substituted by the water-bath reflow method; Acetonitrile-water mobile phase can be substituted by acetonitrile-0.1% phosphoric acid solution mobile phase.
In the content assaying method of jasminoidin of the present invention, linear relationship is investigated evidence: jasminoidin concentration is good linear relationship with trap in the 0ug/ml-76ug/ml scope.Jasminoidin concentration is good linear relationship with trap in the 0-76ug/ml scope.Precision experimental result proof precision test average peak area is 158073, and RSD=1.28% shows that precision is good.Stability experiment proves: need testing solution is measured in back 12 hours of preparation, and the result is stable, and reference substance solution is measured in back 12 hours in preparation, and the result is stable.The repeatability experimental result shows that repeatability is good.The average recovery experimental result shows that the response rate is good.
Capsule is by extraction process and moulding process, dose is reduced, and medicine is clean and tidy, attractive in appearance, it is also very convenient to swallow easily, carry, transport, and control of microorganisms is convenient and easy, clathrate process by volatile oil can be complete its volatile ingredient of preservation, make its stability strong.Following pharmacy and pharmacodynamic experiment example are used to further specify but are not limited to the present invention.
Experimental example 1: the medical material state that feeds intake is investigated
In this prescription, Rhizoma Chuanxiong, Rhizoma Atractylodis contain volatile oil, pulverize to the easily gelatinizing in leaching process of powdered material, therefore consider that block medical material feeds intake or decoction pieces feeds intake, investigate the state that feeds intake of medical material, the mode of the full prescription of research medical material mixed extraction with the quantities received of volatile oil.The results are shown in Table 1
The feed intake investigation of state of table 1 medical material
| The medical material character | The volatile oil of every 100g medical material must be measured |
| Decoction pieces | 0.60ml |
| 0.58ml | |
| 0.64ml | |
| Block | 0.34ml |
| 0.30ml | |
| 0.33ml |
As shown in Table 1, decoction pieces feed intake with block medical material feed intake volatile oil receive aspect have than big-difference, therefore select for use with decoction pieces to feed intake.
Experimental example 2: the investigation of extracting the volatile oil amount of water
In the prescription ratio, take by weighing 5 parts of medical materials, every part of 100g is an index with the total recovery rate of volatile oil, adds not commensurability water logging bubble after 1 hour, extracts volatile oil 8 hours, the results are shown in Table 2
The investigation of amount of water during table 2 volatile oil extracts
| Amount of water | 6 times | 8 times | 10 times | 12 times | 20 times |
| Oil yield (%) | 0.49 | 0.62 | 0.62 | 0.63 | 0.62 |
By table 2 as seen, amount of water is bigger to the extraction influence of volatile oil in the prescription, but the above volatile oil that amount of water extracted of 8 times of amounts is approaching.Because prescription belongs to mixed extraction, Massa Medicata Fermentata easily becomes pasty state after decocting, therefore consider factors such as filtration, selects for use 10 times of water gagings to extract volatile oil.
Experimental example 3: the investigation of volatile oil extraction time
In the prescription ratio, take by weighing 3 parts of medical materials, every part of 200g is an index with the total recovery rate of volatile oil, the water logging bubble that adds 10 times of amounts extracted volatile oil after 1 hour, write down oil yield and the accumulative total oil-collecting ratio of different time, the results are shown in Table 3
The investigation of extraction time during table 3 volatile oil extracts
By table 3 as seen, the medicine in the prescription extracts oil complete when extracting 8 hours substantially, in the time of 6 hours, extraction rate reached is to 0.55%, and the oil-collecting ratio of accumulative total has reached 90%, in order to save production cost and the energy, shorten the production cycle, the extraction time of determining volatile oil is 6 hours.
Experimental example 4: the research of extraction process route
Take by weighing medical material 200g in the prescription ratio, wherein Fructus Gardeniae is 40g, extracts respectively by 3 process routes, measures the wherein content of jasminoidin with the HPLC method, and in conjunction with the content of jasminoidin in dried cream yield and the medical material, calculates the rate of transform of jasminoidin.The results are shown in Table 5.
The setting of table 4 process route
| Process route | Extracting method |
| 1 | Medical material adds 10 times of amounts of water, decocts 3 times, each 1 hour, receives cream. |
| 2 | Medical material adds ethanol 8 amounts, refluxes 3 times, each 1 hour, receives cream. |
| 3 | Medical material adds 10 times of amounts of water, decocts 3 times, and each 1 hour,, decocting liquid concentrates receives cream, adds 4 times of amount 90% ethanol precipitations, reclaims ethanol, receives cream. |
Three process route result of the tests of table 5
| Process route | The result | |||
| The content of jasminoidin (%) in the medical material | The content of jasminoidin (%) in the extractum | Receive cream rate (%) | The jasminoidin rate of transform (%) | |
| 1 | 2.17 | 4.6 | 33.6 | 71.2 |
| 2 | 2.17 | 6.2 | 26.1 | 74.6 |
| 3 | 2.17 | 9.1 | 15.2 | 63.7 |
Table 5 shows that the jasminoidin rate of transform of 3 kinds of extracting method is all higher, but the yield of dry extract differs greatly, and considers that from capsular moulding process decoction and alcohol sedimentation technique is comparatively reasonable.
Experimental example 5: the research of extraction process by water
Extract later extraction process by water at volatile oil and adopt orthogonal design, adding the water multiple, decocting time, the decoction number of times is a factor, every factor is got 3 levels, carries out L
9(3
4) orthogonal test, that adopts HPLC mensuration jasminoidin must measure (jasminoidin content * receipts cream rate) as evaluation index.The results are shown in Table 6, table 7.
Table 6 extraction process by water is investigated the factor level table
| Level | Factor | |||
| A amount of water (multiple) | B decocts number of times (inferior) | The C decocting time (hour) | The D blank | |
| 1 | 8 | 1 | 1 | |
| 2 | 10 | 2 | 2 | |
| 3 | 12 | 3 | 3 | |
Take by weighing prescription 4500g in proportion, after the volatile oil extraction finished, the leaching medicinal residues were equally divided into 9 parts by quality, and every part of crude drug content is 500g, and the extraction process by water of determining by table 7 extracts.
Table 7 extraction process by water is investigated orthogonal test and result
| Gauge outfit design row number | A 1 | B 2 | C 3 | D 4 | Receive cream rate (%) | Jasminoidin content (%) | The evaluation index jasminoidin must be measured (mg) |
| 1 | 1 | 1 | 1 | 1 | 8.2 | 0.84 | 344.4 |
| 2 | 1 | 2 | 2 | 2 | 10.3 | 0.98 | 504.7 |
| 3 | 1 | 3 | 3 | 3 | 11.0 | 0.78 | 429.0 |
| 4 | 2 | 1 | 2 | 3 | 9.4 | 0.80 | 376.0 |
| 5 | 2 | 2 | 3 | 1 | 11.6 | 0.76 | 440.8 |
| 6 | 2 | 3 | 1 | 2 | 8.5 | 0.94 | 399.5 |
| 7 | 3 | 1 | 3 | 2 | 11.3 | 0.72 | 406.8 |
| 8 | 3 | 2 | 1 | 3 | 9.6 | 1.0 | 480.0 |
| 9 | 3 | 3 | 2 | 1 | 10.8 | 0.82 | 442.8 |
| Ij | 1278.1 | 1127.2 | 1223.9 | 1228.0 | CT＝1624775.1 | ||
| IIj | 1216.3 | 1425.5 | 1323.5 | 1311.0 | |||
| IIIj | 1329.6 | 1271.3 | 1276.6 | 1285.0 | |||
| R | 113.3 | 298.3 | 99.6 | 83.0 | |||
The result is carried out variance analysis, and closing from variance analysis factor primary and secondary is that B＞A＞C optimal scheme is B
2A
3C
2Promptly use 12 times of water gagings, decoct each 2 hours 2 times.But find in the variance analysis, except that factor B difference, do not have significant difference between A factor and each level of C factor, from production cost and production cycle, water is suggested plans and is selected B for use
2A
1C
1, promptly decocting 2 times with 8 times of water gagings, the time is 1 hour.
Experimental example 6: extract dry technology is investigated
Carry out the investigation of 3 kinds of drying meanss to extracting extractum, the results are shown in Table 8
Table 8 extract dry technology is investigated
| Drying means | Drying effect |
| Spray drying | Easily bond, in bulk can't carry out drying smoothly |
| Drying under reduced pressure | Easily dry, dry thing is a lumps |
| The normal pressure forced air drying | Be difficult for dry |
Product carries out drying under reduced pressure respectively under 40 ℃, 50 ℃, 60 ℃ conditions; As a result, the product of 40 ℃ and 50 ℃ following drying under reduced pressure gained is pale brown color, and loss on drying is lower than 5%; The product surface of 60 ℃ of following drying under reduced pressure gained is a buff, and bonds.Take all factors into consideration drying efficiency and drying effect, product drying is advisable with 40 ℃～50 ℃ drying under reduced pressure.
Experimental example 7: alcohol precipitation process research
Take by weighing medical material 4500g in proportion, extract leaching water extract by volatile oil extraction and the extraction process by water determined, be concentrated into the thick paste of different relative densities (60 ℃), be equally divided into 9 parts by quality, every part of crude drug content is 500g, and wherein the amount of Fructus Gardeniae medical material is 100g.Alcohol precipitation process adopts orthogonal design, concentration of alcohol, and the ethanol consumption, aqueous extract density, time of repose is the investigation factor, every factor is got 3 levels, carries out L
9(3
4) orthogonal test, adopt the HPLC method to measure the content of jasminoidin, receive the cream rate as evaluation index.The results are shown in Table 9, table 10.
Table 9 alcohol precipitation process is investigated the factor level table
| Level | Factor | |||
| A concentration of alcohol (%) | B ethanol consumption | C aqueous extract density (60 ℃) | The D time of repose | |
| 1 | 90 | 10 | 1.15 | 24 |
| 2 | 80 | 6 | 1.10 | 12 |
| 3 | 70 | 4 | 1.05 | 8 |
Comprehensive grading=jasminoidin content (examination)/jasminoidin content (max) * 80%+ receives cream rate (examination)/receipts cream rates (max) * 20%
Table 10 alcohol precipitation process is investigated orthogonal test and result
| Gauge outfit design row number | A 1 | B 2 | C 3 | D 4 | Evaluation index | ||
| Jasminoidin content (%) | Receive cream rate (%) | Comprehensive grading | |||||
| 1 | 1 | 1 | 1 | 1 | 2.32 | 9.3 | 91.34 |
| 2 | 1 | 2 | 2 | 2 | 2.38 | 13.2 | 98.17 |
| 3 | 1 | 3 | 3 | 3 | 2.22 | 13.3 | 92.77 |
| 4 | 2 | 1 | 2 | 3 | 2.22 | 10.1 | 88.87 |
| 5 | 2 | 2 | 3 | 1 | 2.05 | 11.2 | 84.35 |
| 6 | 2 | 3 | 1 | 2 | 2.21 | 14.2 | 93.52 |
| 7 | 3 | 1 | 3 | 2 | 2.12 | 9.4 | 84.57 |
| 8 | 3 | 2 | 1 | 3 | 1.78 | 14.8 | 79.43 |
| 9 | 3 | 3 | 2 | 1 | 1.52 | 16.4 | 72.41 |
| Ij | 282.27 | 264.77 | 264.29 | 248.10 | CT＝68544.3 | ||
| IIj | 266.74 | 261.94 | 259.44 | 276.25 | |||
| IIIj | 236.40 | 258.70 | 261.68 | 261.06 | |||
| R | 45.87 | 2.83 | 2.23 | 28.15 | |||
The result is carried out variance analysis, and closing from variance analysis factor primary and secondary is A＞B＞D＞C, and good scheme is A1B1C1D2, from variance analysis, find out, there was no significant difference between each level of B, C, D factor from producing actual and saving time, is investigated and is selected A
1B
3C
1D
2Promptly add 4 times of amounts of ethanol of 90%, left standstill 12 hours.
Experimental example 8: inclusion essential oil technology is investigated
The preservation of volatile oil in preparation, form with clathrate saves as good, the definite of clathrate process screens with Orthogonal Experiment and Design, according to the influence factor of clathrate process, the rate of charge of selective volatilization oil and beta-schardinger dextrin-, enclose temperature, mixing time, mixing speed is a factor, and every factor is got 3 levels, carries out L
9(3
4) orthogonal test, adopt clathrate recovery rate and inclusion rate as evaluation index.The results are shown in Table 11, table 12
The design of table 11 inclusion essential oil technology quadrature gauge outfit
| Level | Factor | |||
| The rate of charge of A volatile oil and beta-schardinger dextrin- | The B whipping temp (℃) | C mixing speed (rpm) | D mixing time (h) | |
| 1 | 1∶8 | 40 | 400 | 1 |
| 2 | 1∶10 | 50 | 800 | 2 |
| 3 | 1∶12 | 60 | 1200 | 3 |
Table 12 inclusion essential oil technology is investigated orthogonal test and result
| Gauge outfit design row number | A 1 | B 2 | C 3 | D 4 | Inclusion rate (%) | Clathrate recovery rate (%) | Comprehensive grading |
| 1 | 1 | 1 | 1 | 1 | 79.0 | 79.3 | 89.73 |
| 2 | 1 | 2 | 2 | 2 | 82.0 | 83.0 | 93.37 |
| 3 | 1 | 3 | 3 | 3 | 87.0 | 87.0 | 98.71 |
| 4 | 2 | 1 | 2 | 3 | 88.2 | 79.3 | 97.03 |
| 5 | 2 | 2 | 3 | 1 | 84.3 | 80.5 | 94.35 |
| 6 | 2 | 3 | 1 | 2 | 86.8 | 88.0 | 98.89 |
| 7 | 3 | 1 | 3 | 2 | 86.1 | 68.0 | 91.52 |
| 8 | 3 | 2 | 1 | 3 | 80.1 | 80.5 | 91.01 |
| 9 | 3 | 3 | 2 | 1 | 81.4 | 75.5 | 90.34 |
| Ij | 281.81 | 278.28 | 279.63 | 274.42 | CT＝79326.72 | ||
| IIj | 290.27 | 278.73 | 280.74 | 283.78 | |||
| IIIj | 272.87 | 287.94 | 284.58 | 286.75 | |||
| R | 17.4 | 9.66 | 4.95 | 12.33 | |||
The result is carried out variance analysis, and closing from variance analysis factor primary and secondary is that A＞D＞B＞C optimal scheme is A
2D
3B
3C
3The rate of charge that is volatile oil and beta-schardinger dextrin-is 1: 10, and 60 ℃ of following insulated and stirred, mixing speed are 1200rpm, and mixing time is 3 hours.Find, not have significant difference between each level of all the other factors in the variance analysis except that factor A has the significant difference, B, C, production cycle and energy consumption difference are little between each level of D, so preferred plan is selected A
2D
3B
3C
3
Experimental example 9: the dosage of adjuvant is selected experiment
Because we have used beta-cyclodextrin inclusion compound volatile oil in preparation, and the amount ratio of the yield of extractum and beta-schardinger dextrin-is more constant.Therefore, beta-schardinger dextrin-can play certain diluting effect in granule, can reduce the consumption of supplementary product starch, the according to the form below mixed proportion, and 90% alcohol granulation, the consumption of investigation starch the results are shown in Table 13.
| The extract powder consumption | 100g | 100g | 100g | 100g |
| The beta-schardinger dextrin-consumption | 50g | 50g | 50g | 50g |
| The starch consumption | - | 50g | 100g | 150g |
| Adjuvant: extract powder | 0.5∶1 | 1∶1 | 1.5∶1 | 2∶1 |
| The granule situation | Viscosity is big, can't granulate | Can granulate, particle shape is good | Can granulate, particle shape is good | Can granulate, particle shape is good |
By last table 13 as seen, adjuvant amount and extract powder amount can satisfy the requirement of granulation when 1: 1 left and right sides, consider capsular drug loading and dose, and the consumption of starch should be not excessive.
Experimental example 10: the research of particle binders
Ethanol is as particulate binding agent, and its concentration is very big to the granulating efficiency influence, the existing concentration of alcohol of granulating of investigating.Extract powder, beta-schardinger dextrin-, starch by the equivalent dilution method mix homogeneously that progressively increases, are sprayed into ethanol, make soft material, overstock, make granule, investigate the granule situation by 20 order medicines sieve.The results are shown in Table 14
Table 14 is granulated with the investigation of concentration of alcohol
| Concentration of alcohol (%) | 80 | 90 | 95 | Dehydrated alcohol |
| The granulation situation | Bonding, the difficulty of granulating | All right, uniform particles | The soft material agglomerate looses crisp, and grain forming is poor | Be difficult to form soft material |
By last table 14 as seen, comparatively desirable with 90% alcohol granulation.
Experimental example 11: the research of prill drying
Contain beta-schardinger dextrin-in the granule of preparation, it is higher with concentration of ethanol to granulate, and therefore exsiccant temperature can not be too high, and temperature is advisable with 50 ℃.
Table 15 prill drying is investigated
| Drying means | Electrothermal drying | The electric heating forced air drying |
| The granule situation | A small amount of caking is arranged | The minute quantity caking is arranged |
| Drying time (hour) | 2.5 hour | 1.5 hour |
Therefore particulate drying means is the electric heating forced air drying, and be 1.5 hours drying time.
Experimental example 12: the selection research of granule adjuvant
Particulate angle of repose is relatively large, and flowability remains to be improved, and therefore needs to add certain lubricant and improves its flowability, selects for use micropowder silica gel as lubricant.Get a certain amount of granule, press different proportion and add micropowder silica gel, investigate its angle of repose, the results are shown in Table 16
The screening of table 16 micropowder silica gel consumption
| Micropowder silica gel additional proportion (%) | 0.5 | 1.0 | 1.5 | 2.0 | 2.5 | 3.0 |
| Angle of repose | 39 | 38 | 36 | 36 | 35 | 34 |
By last table 16 as seen, when the consumption of micropowder silica gel 1.5% when above, particulate flowability is more satisfactory, so the consumption of micropowder silica gel is chosen in about 1.5%.
Experimental example 13: the qualitative identification test of Fructus Gardeniae
Get and bring up composite preparation capsule 's content 2g more, pulverize, added methanol 20ml ultrasonic 30 minutes, filter, filtrate concentrates near doing, and adds methanol 1ml and makes dissolving, as need testing solution.Other gets Fructus Gardeniae control medicinal material 1g, shines medical material solution in pairs with legal system.Four kinds of photograph thin layer chromatography tests that development system screens have been investigated in test:
A. getting above-mentioned two kinds of each 10ul of solution, put respectively on same silica gel G plate, is developing solvent with chloroform-methanol-ammonia (4: 1: 0.1), launches, takes out, dries.Spray is with 10% sulphuric acid ethanol liquid, and hot blast blows to speckle and develops the color.
B. get above-mentioned two kinds of each 10ul of solution, put respectively on same silica gel G plate, with ethyl acetate-acetone-formic acid-water (5: 3: 1: be developing solvent 1), launch, take out, dry.Spray is with 10% ethanol solution of sulfuric acid, and hot blast blows to speckle and develops the color.
C. get above-mentioned two kinds of each 10ul of solution, put respectively on same silica gel G plate, with butyl acetate-butanone-formic acid-water (5: 3: 1: be developing solvent 1), launch, take out, dry.Spray is with 10% ethanol solution of sulfuric acid, and hot blast blows to speckle and develops the color.
D. get above-mentioned two kinds of each 10ul of solution, put respectively on same silica gel G plate, with ethyl acetate-butanone-formic acid-water (5: 3: 2: be developing solvent 1), launch, take out, dry.Spray is with 10% ethanol solution of sulfuric acid, and hot blast blows to speckle and develops the color.
The result shows that expansion and the separating effect of development system B are better, determines the method that B differentiates for Fructus Gardeniae TLC.
According to said method carry out, repeat three batch samples, in the test sample chromatograph, all showing the speckle of same color with the corresponding position of reference substance chromatograph.
Experimental example 14: the qualitative identification test of Rhizoma Atractylodis
Rhizoma Atractylodis mainly contain atisine chloride atractydin etc., get YUEJU JIAONANG content 4g, pulverize, and the 30ml that adds diethyl ether, reflux 1 hour is put coldly, filters, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, as need testing solution.Other gets Rhizoma Atractylodis control medicinal material 1g, shines medical material solution in pairs with legal system.
Test has been investigated four kinds of development systems and has been screened, and tests according to thin layer chromatography:
A. with petroleum ether (60～90 ℃)-ethyl acetate (20: 1)) be developing solvent, launch, taking-up is dried, and spray is with 10% sulphuric acid ethanol liquid of 5% paradime thylaminobenzaldehyde, and it is clear that hot blast blows to the speckle colour developing.
B. be developing solvent with petroleum ether (60～90 ℃), launch that taking-up is dried, spray is with 10% sulphuric acid ethanol liquid of 5% paradime thylaminobenzaldehyde, and it is clear that hot blast blows to the speckle colour developing.
C. launch with toluene-ethyl acetate (95: 5), put ultra-violet lamp (365nm) and locate to inspect.
D. be developing solvent with benzene-ethyl acetate-normal hexane (3: 3: 4), launch, take out, dry, put uviol lamp (254nm) and locate to inspect.
The result shows that expansion and the separating effect of development system B are better, determines the method that B differentiates for Rhizoma Atractylodis TLC.
According to said method carry out, repeat three batch samples, all showing the speckle of same color with the corresponding position of control medicinal material chromatograph.
Experimental example 15: the character identification test of Rhizoma Chuanxiong
Rhizoma Chuanxiong mainly contains ligustrazine, ferulic acid etc., and test has been investigated two kinds of methods and screened, and tests according to thin layer chromatography:
A. get and bring up composite preparation capsule 's content 4g more, pulverize, the 30ml that adds diethyl ether, reflux 1 hour is put coldly, filters, and medicinal residues are standby, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving as test sample liquid.Other gets Rhizoma Chuanxiong control medicinal material 1g, shines medical material solution in pairs with legal system.Drawing above-mentioned two kinds of each 10ul of solution, put respectively on same silica gel g thin-layer plate, is developing solvent with normal hexane-ethyl acetate (9: 1), launches, and takes out, and dries.Put under the ultra-violet lamp (365nm) and inspect.
B. get and bring up composite preparation capsule 's content 4g more, pulverize, add ethyl acetate 20ml, supersound process 20 minutes filters, and filtrate is concentrated into 1ml as need testing solution.Other gets Rhizoma Chuanxiong control medicinal material 1g, shines medical material solution in pairs with legal system.Drawing above-mentioned two kinds of each 10ul of solution, put respectively on same silica gel g thin-layer plate, is developing solvent with normal hexane-ethyl acetate (9: 1), launches, and takes out, and dries.Put under the ultra-violet lamp (365nm) and inspect.
The result shows that expansion and the separating effect of development system B are better, determines the method that B differentiates for Rhizoma Chuanxiong TLC.
According to said method carry out, repeat three batch samples, all showing the speckle of same color with the corresponding position of control medicinal material chromatograph.
Experimental example 16: the character identification test of Rhizoma Cyperi
Get and bring up composite preparation capsule 's content 3g more, pulverize, the 20ml that adds diethyl ether, ultrasonic 20 minutes, filter, filtrate is concentrated into 1ml as need testing solution.Other gets Rhizoma Cyperi control medicinal material 2g, shines medical material solution in pairs with legal system.
Test has been investigated three kinds of development systems and has been screened, and tests according to thin layer chromatography:
A. be developing solvent with ethyl acetate-petroleum ether (15: 85), launch, take out, dry.Spray is with 5% phosphomolybdic acid-alcoholic solution, and 105 ℃ are dried by the fire to speckle and develop the color.
B. be developing solvent with ethyl acetate-benzene-glacial acetic acid (5: 92: 5), launch, take out, dry.Putting uviol lamp (254nm) locates down to inspect.
C. be developing solvent with ethyl acetate-petroleum ether (25: 75), launch, take out, dry.Spray is with 5% phosphomolybdic acid ethanol solution, and 105 ℃ are dried by the fire to speckle and develop the color.
The result shows that expansion and the separating effect of development system A are better, determines the method that A differentiates for Rhizoma Cyperi TLC.
According to said method carry out, repeat three batch samples, all showing the speckle of same color with contrast chromatograph corresponding position.
Experimental example 17: the assay test of Fructus Gardeniae medical material
Detect the selection of wavelength
Get the jasminoidin reference substance, add 10% methanol aqueous solution, with 10% methanol aqueous solution is blank, respectively at scanning in 200～400nm wave-length coverage, by scintigram as seen, the jasminoidin reference substance has absorption maximum at the 238-239nm place, and blank reagent does not have absorption at this wavelength, selects 238nm as detecting wavelength.
The selection of extraction solvent
Sample thief (lot number: 020201) about 0.1g3 part, accurate claim surely, put in the 50ml volumetric flask, add methanol respectively, 70% ethanol, the about 40ml of ethyl acetate, supersound process 30 minutes is put coldly, supplies volume with corresponding solvent, shakes up filtration.Measure jasminoidin content, the results are shown in Table 17.
The selection of table 17 extraction solvent
| Extraction solvent | Methanol | 70% ethanol | Ethyl acetate |
| Jasminoidin content (%) | 1.22 | 1.20 | 1.18 |
As known from the above, the extraction effect of 3 kinds of solvents is approaching, and in the chromatography, methanol uses the most extensive, therefore selects for use methanol as extracting solvent.
The selection of extracting method
Sample thief (lot number: 020201) about 0.1g2 part, the accurate title, decide, and puts in the 50ml round-bottomed flask, adds methanol 30ml respectively, adopts following 2 kinds of methods to handle sample, the results are shown in Table 18:
A. supersound process is 30 minutes, puts coldly, filter to the 50ml volumetric flask, and the methanol wash flask, washing liquid is incorporated in the volumetric flask, and standardize solution shakes up, and filters.Measure jasminoidin content.
B. the water-bath reflux, extract, is 30 minutes, puts coldly, filter to the 50ml volumetric flask, and the methanol wash flask, washing liquid is incorporated in the volumetric flask, and standardize solution shakes up, and filters.Measure jasminoidin content.
The selection of table 18 extracting method
| Extracting method | Supersound process | Water-bath refluxes |
| Jasminoidin content (%) | 1.20 | 1.22 |
More than test explanation, the effect of reflux, extract, and supersound process is approaching.
The selection of extraction time
Sample thief (lot number: 020201) about 0.1g4 part, the accurate title, decide, and puts in the 50ml volumetric flask, adds the about 40ml of methanol respectively, and the supersound process sample is 15 minutes respectively, 20 minutes, 30 minutes, 40 minutes, put cold after the ultrasonic end, supply volume with methanol, filter, get subsequent filtrate, promptly.Measure jasminoidin content.The results are shown in Table 19:
The selection of table 19 extraction time
| Extraction time (minute) | 10 | 20 | 30 | 40 |
| Jasminoidin content (%) | 0.97 | 1.20 | 1.21 | 1.21 |
More than test shows, extraction time surpassed after 20 minutes, and extraction effect is approaching, therefore lists text in.
The selection of extraction solvent amount
Sample thief (lot number: 020201) about 0.1g4 part, decide, and with not commensurability methanol supersound process, gets subsequent filtrate and measure jasminoidin content by accurate the title.The results are shown in Table 20
The selection of table 20 extraction solvent amount
| Solvent amount (ml) | 10 | 20 | 30 | 40 |
| Jasminoidin content (%) | 1.14 | 1.22 | 1.21 | 1.22 |
More than test shows that when sampling amount was 0.1g, the solvent amount did not have influence to assay when 20ml is above, binding capacity bottle specification, so the amount of extraction solvent is defined as 25ml.Consider the concentration and the detectability of sample, extracting solution is good about 2 times to dilute, so after the extracting solution filtration, dilutes 2 times as need testing solution.
The selection of mobile phase:
Experiment is respectively with Diamonsil C
185u 4.6mm * 200mm post is analytical column, investigated the separating effect of two kinds of mobile phases to sample, and the result is as follows:
A. be mobile phase with acetonitrile-water (15: 85), flow velocity: 1ml/ minute, research experiment, result reached satisfied separating effect, and main peak has reached baseline separation, the peak shape symmetry.
B. be mobile phase with acetonitrile-0.1% phosphoric acid solution (17: 83), flow velocity: 1ml/ minute, research experiment, result reached satisfied separating effect, and main peak has reached baseline separation, the peak shape symmetry.
More than two kinds of mobile phases all can reach satisfied separating effect, but the preparation of B mobile phase is comparatively loaded down with trivial details, historical facts or anecdotes is tested and is finally selected for use acetonitrile-water (15: 85) to be mobile phase, flow velocity 1ml/ minute, column temperature: 35 ℃.
The selection of chromatographic column
The separating effect of two kinds of analytical columns to sample investigated in experiment respectively, and be as follows:
A. with Diamonsil C
185u 4.6mm * 200mm is an analytical column, is mobile phase with acetonitrile-water (15: 85), and flow velocity: 1ml/ minute, research experiment, result reached satisfied separating effect, and main peak has reached baseline separation, the peak shape symmetry.
B. with Kromasil C
185u 4.6mm * 200mm is an analytical column, is mobile phase with acetonitrile-water (15: 85), and flow velocity: 1ml/ minute, research experiment, result reached satisfied separating effect, and main peak has reached baseline separation, the peak shape symmetry.
The separating effect of two kinds of analytical columns all can meet the demands, and from this breadboard use experience, finally selects Diamonsil C for use
185u 4.6mm * 200mm is an analytical column.
Following pharmacodynamic experiment example is used to further specify but is not limited to the present invention.
Experimental example 18: anti-reserpine blepharoptosis depression model test
Choose 72 Kunming mouses, be all malely, body weight 18～22g is divided into 6 groups at random by body weight, and multiple dosing is pressed the listed medicine of table 21 and dosage gastric infusion every day 1 time, each treated animal 60min after administration, lumbar injection reserpine injection 2mg/kg.Continuous 10 days, on 10th, injection back 60min was put in mice and observes 2min on the support, observed in each treated animal eyelid and closed animal number over half at least, with FISHER Precision Test statistics, the results are shown in Table 21.
Table 21 YUEJU extractum multiple dosing causes the influence of blepharoptosis to the mice reserpine
| Group | Dosage * natural law (g/kg * d) | Mus number (only) | Eyelid is closed number of animals over half (only) at least |
| The distilled water group | -- | 12 | 12 |
| The fluoxetine group | 0.02×10 | 12 | 2** |
| The Yueju Wan group | 6×10 | 12 | 8 |
| The YUEJU extractum group | 6×10 | 12 | 7* |
| The YUEJU extractum group | 3×10 | 12 | 9 |
| The YUEJU extractum group | 1.5×10 | 12 | 8 |
Annotate: each administration group and distilled water group be * P＜0.05 * * P＜0.01 relatively
Table 21 shows, YUEJU extractum 6g/kg organizes administration in continuous 10 days and the mice reserpine is caused blepharoptosis has remarkable inhibitory action (P＜0.05).
Experimental example 19: anti-reserpine causes motion can not the depression model test
Choose 72 Kunming mouses, be all male, Mus 7～8 weeks of age, body weight 18～22g is divided into 6 groups at random by body weight, and multiple dosing test is pressed the listed medicine of table 22 and dosage gastric infusion every day once, continuous 7 days, observe the number that still stays in each treated animal in the 30sec in the filter paper,, the results are shown in Table 22 with FISHER Precision Test statistics.
Table 22 YUEJU extractum multiple dosing causes akinetic influence to the mice reserpine
| Group | Dosage * natural law (g/kg * d) | Mus number (only) | Still stay in the number (only) in the filter paper in the 30sec in each treated animal |
| The distilled water group | -- | 12 | 12 |
| The fluoxetine Capsules group | 0.02×7 | 12 | 1*** |
| The Yueju Wan group | 6×7 | 12 | 5** |
| The YUEJU extractum group | 6×7 | 12 | 3*** |
| The YUEJU extractum group | 3×7 | 12 | 7* |
| The YUEJU extractum group | 1.5×7 | 12 | 8 |
Annotate: each administration group and distilled water group be * P＜0.05 * * P＜0.01 * * * P＜0.001 relatively
Table 22 shows that YUEJU extractum 6,3g/kg dosage group and the administration of Yueju Wan group caused motion to the mice reserpine and can not have extremely remarkable, obvious and remarkable antagonism (P＜0.001, P＜0.05 or P＜0.001) respectively after 7 days.
Experimental example 20: the acquired desperate depression model test of mouse tail suspension method
Choose 72 Kunming mouses, be all malely, in Mus 8～9 weeks of age, body weight 18～22g is divided into 6 groups at random by body weight, 12 every group.Single-dose is pressed the listed medicine of table 23 and dosage gastric infusion once, each treated animal 30min after administration, use rubberized fabric adhere on the pvc pipe of diameter 1cm apart from sharp 1cm place mouse tail, do not make the mouse tail distortion folding, built on stilts then pvc pipe, mice is hangs shape by the feet, head separates with dividing plate between per two mices apart from table top 5cm, and it is not disturbed mutually, observe the motionless time (stationarity indices is that animal all limbs except that breathing are all motionless) of accumulative total in every animal 6min, the results are shown in Table 23.Multiple dosing is pressed the listed medicine of table 20 and dosage gastric infusion every day once, continuous 10 days, the results are shown in Table 24.
Table 23 YUEJU extractum single-dose is to the influence of mouse tail suspension test
Annotate: each administration group and distilled water group be * P＜0.05 * * P＜0.01 * * * P＜0.001 relatively
Table 23 shows that YUEJU extractum 6～1.5g/kg dosage group single-dose has significantly, obviously and obviously shortens (P＜0.01, P＜0.05 or P＜0.05) respectively to the mouse tail suspension dead time.
Table 24 YUEJU extractum multiple dosing is to the influence of mouse tail suspension test
Annotate: each administration group and distilled water group be * P＜0.05 * * P＜0.01 * * * P＜0.001 relatively
Table 24 shows, the administration of YUEJU extractum 6～1.5g/kg dosage group is after 10 days, and the mouse tail suspension dead time is had extremely significantly, extremely significantly and obviously shortens (P＜0.001, P＜0.001 or P＜0.05) respectively.
Experimental example 21: behavioristics's test of chronic stress rat depression model
Choose 70 of SD kind rats, male and female half and half, in Mus 9～10 weeks of age, body weight 180～220g is divided into 7 groups by the body weight random stratified, 10 every group.Except that the normal control treated animal, orphan of the whole every cages of modeling animal supports, accept 21 days various stress stimulations, comprise (4 ℃ of frozen water swimming, 5min), press from both sides tail (3min), taboo water (40h), fasting (40h), pairing raising and humidity, fetter and illumination stimulation in all night average every kind of stimulation 2～3 times.5 raisings of the every cage of normal rats will not any stimulation.Each administration group is pressed medicine shown in the table 25 and dosage gastric infusion simultaneously in modeling, continuous 21 days.Adopt the observed behavior of Open-field method.This tests used spacious case is cube, and 25 of being equated by area of high 40cm, length and width 80cm, perisporium, bottom surface form, and divide with white line.Passing through the bottom surface block number with animal is horizontal anomalous movement (crossing) score, serves as vertical movable (rearing) score with upright number of times.Observed in the 22nd day, every zoometry 1 time, each minute is 3min, count level activity score and vertical activity score.The results are shown in Table 25.
Table 25 YUEJU extractum is to the influence of chronic stress depression model rat Open-field judicial act
Annotate: 1. model group matched group and normal control group are relatively
▲ ▲ ▲P＜0.001
2. each administration group and model compare * P＜0.05, * * P＜0.01, * * * P＜0.001
Table 25 result shows, the horizontal movement of chronic stress depression model rat and all extremely significantly minimizings (P＜0.001) that moves both vertically, YUEJU extractum 6～1.5g/kg dosage group respectively can be obviously or is significantly resisted horizontal movement and reduce (P＜0.05, P＜0.05 or P＜0.01), obviously or significantly resists the minimizing (P＜0.05, P＜0.01 or P＜0.01) that moves both vertically respectively.
The test of trembling of experimental example 22:L-5-oxitriptan induced mice
Select 90 Kunming mouses for use, male and female half and half, in Mus 8～9 weeks of age, body weight 18～22g is divided into 7 groups by body weight and sex random stratified.Respectively organize the mouse stomach administration 1 time by medicine shown in the table 26 and dosage.60min after the administration, each Mus lumbar injection 5-hydroxyryptophan 200mg/kg (not causing the maximum dose level that mice is trembled), subsequently with mice is single is placed in the cage (16 * 27cm), observe and occur in the 20min trembling the number of animals of (characteristic occurring with animal, to get rid of a behavior be pointer).With FISHER Precision Test statistics, the results are shown in Table 26.
Table 26 YUEJU extractum is to the influence of the 5-hydroxyryptophan effect of trembling
| Group | Dosage * number of times (g/kg * c) | Mus number (only) | Mus number (only) trembles |
| Distilled water+5-hydroxyryptophan group | -- | 10 | 1 |
| Distilled water+fluoxetine group | 0.2mg×1 | 10 | 0 |
| Fluoxetine group+5-hydroxyryptophan | 0.2mg×1 | 10 | 9*** |
| Distilled water+YUEJU extractum group | 6×1 | 10 | 0 |
| Distilled water+Yueju Wan group | 6×1 | 10 | 0 |
| Yueju Wan+5-hydroxyryptophan group | 6×1 | 10 | 4 |
| YUEJU extractum+5-hydroxyryptophan group | 6×1 | 10 | 6 |
| YUEJU extractum+5-hydroxyryptophan group | 3×1 | 10 | 5 |
| YUEJU extractum+5-hydroxyryptophan group | 1.5×1 | 10 | 3 |
Annotate: each administration group and distilled water+5-hydroxyryptophan group is * * * P＜0.001 relatively
Table 26 result shows, only give mice L-5-oxitriptan or be subjected to reagent (YUEJU extractum and fluoxetine capsule), trembling does not appear in animal, and after being subjected to reagent, give 5-hydroxyryptophan again, then along with the increase of YUEJU extractum dosage, the number of animals that occurs trembling increases, but no significant difference (P＞0.05) illustrates that YUEJU extractum has the trend of strengthening the 5-hydroxyryptophan effect of trembling.
Experimental example 23: strengthen the test of levodopa behavior effect
Select 90 Kunming mouses for use, male and female half and half, in Mus 8～9 weeks of age, body weight 18～22g is divided into 7 groups by body weight and sex random stratified.Respectively organize the mouse stomach administration 1 time by medicine shown in the table 27 and dosage.60min after the administration, each Mus lumbar injection levodopa 200mg/kg (not causing the maximum dose level that mice is run) is placed in the cage mice is single subsequently, observes the number of animals that occurs running in the 30min.With the FISHER Precision Test, the results are shown in Table 27.
Table 27 YUEJU extractum is to the influence of levodopa behavior effect
| Group | Dosage * number of times (g/kg * c) | Mus number (only) | Mus number (only) trembles |
| Distilled water+levodopa group | -- | 10 | 0 |
| Distilled water+fluoxetine Capsules group | 0.2mg×1 | 10 | 0 |
| Fluoxetine capsule+levodopa group | 0.2mg×1 | 10 | 8*** |
| Distilled water+Yueju Wan group | 6×1 | 10 | 0 |
| Distilled water+YUEJU extractum group | 6×1 | 10 | 0 |
| Yueju Wan+levodopa group | 6×1 | 10 | 3 |
| YUEJU extractum+levodopa group | 6×1 | 10 | 4 |
| YUEJU extractum+levodopa group | 3×1 | 10 | 2 |
| YUEJU extractum+levodopa group | 1.5×1 | 10 | 0 |
Annotate: each administration group and distilled water+levodopa group is * * * P＜0.001 relatively
Table 27 result shows, only give the mice levodopa or be subjected to reagent (YUEJU extractum and fluoxetine capsule), trembling does not appear in animal, and after being subjected to reagent, give levodopa again, then have the part animal to make little runs to and fro, and along with the increase of YUEJU extractum dosage, the number of animals that occurs running increase along cage, (P＞0.05) illustrates that YUEJU extractum has the effect trend of strengthening the levodopa behavior effect.
Experimental example 24: YUEJU extractum is to the influence of spontaneous activity in mice
Select 84 Kunming mouses for use, male and female half and half, in Mus 8～9 weeks of age, body weight 18～22g is divided into 7 groups at random, and 12 every group, fasting be can't help water 12 hours before the test, and test arrangement carried out night, and laboratory temperature is controlled at 24～26 ℃.Press listed medicine of table 28 and dosage and irritate stomach once.0.5h after the administration measures spontaneous activity in mice.Assay method: after mice put into the complete behavioral activity analyzer of ZL-1 computer control toy and adapt to 1min, measure the movable number of times in its 3min, be calculated as follows calm rate, the results are shown in Table 28.
Table 28 YUEJU extractum is to the influence of spontaneous activity in mice
| Group | Dosage (g/kg) | Mus number (only) | Movable number of times (inferior/3min) | Calm rate (%) |
| The distilled water group | The isometric(al) distilled water | 12 | 135.8±43.4 | -- |
| The fluoxetine group | 0.02 | 12 | 128.7±21.3 | 5.28 |
| The estazolam group | 0.01 | 12 | 35.3±14.1** | 73.99 |
| The Yueju Wan group | 6×1 | 12 | 66.8±14.6** | 50.8 |
| The YUEJU extractum group | 6×1 | 12 | 52.7±27.4** | 61.2 |
| The YUEJU extractum group | 3×1 | 12 | 101.4±33.8* | 25.34 |
| The YUEJU extractum group | 1.5×1 | 12 | 116.4±20.4 | 14.29 |
Annotate: each administration group and distilled water group be * P＜0.05 * * P＜0.01 relatively
Table 28 shows that YUEJU extractum 6 and 3g/kg dosage group have respectively significantly and obvious suppression effect (P＜0.01 or P＜0.05) spontaneous activity in mice.
Experimental example 25: the collaborative hypnosis test of threshold dose pentobarbital sodium
Choose 72 Kunming mouses, male and female half and half, Mus 8～9 weeks of age, body weight 18～22g, be divided into 6 groups at random, every group 12, irritate stomach respectively once by the listed medicine of table 29 and each group of dosage, behind the 30min, every mouse peritoneal is injected 0.38% pentobarbital sodium 38mg/kg, was time for falling asleep with righting reflex loss more than 1 minute, reverted to the length of one's sleep from the righting reflex loss to the righting reflex, the results are shown in Table 29.
Table 29 YUEJU extractum is worked in coordination with threshold dose pentobarbital sodium syngignoscism
Annotate: each administration group and distilled water group be * * P＜0.01 relatively
Table 29 shows, YUEJU extractum is to the time for falling asleep of threshold dose pentobarbital sodium hypnosis mice and all do not have obvious influence (P＞0.05) length of one's sleep.
Experimental example 26: liver depression model test
Choose 60 SD rats, male and female half and half, in Mus 8～9 weeks of age, body weight 180～200g is divided into 5 groups at random, irritates stomach respectively once a day by the listed medicine of table 30 and each group of dosage, and normal control group and stagnation of liver-QI model group are irritated stomach equal-volume distilled water.Administration began respectively to organize the SD rat and wore mould (single cage raising) 18 days the same day, and mould is two thick 0.2cm, and the red plexiglass of diameter 4cm is formed similar cervical region chains shape mould.
The front and back situation (flounced, grabs and sting cage tool, mould, constantly shout after the observation animal was worn mould, bradykinesia, behavior is slow, and animal eyes is narrowed little, gum is arranged, hair color is withered and yellow, feces is little, dried, less, tail is brownish red and has scale to occur, become thin, lose weight etc.), measured rat spontaneous activity (assay method is with the chronic stress rat model) on the 18th day, and calculate the spontaneous activity increment rate, and get hematometry hemorheological property index from femoral artery.Result's T inspection statistics.
Table 30 YUEJU extractum enrages the influence of liver depression rat model Open-field judicial act to die methods
| Group | Dosage (g/kg) | Mus number (only) | Vertical activity score | The horizontal anomalous movement score |
| The normal control group | -- | 10 | 14±3.4 | 64.6±18.9 |
| The stagnation of liver-QI model group | -- | 10 | 4±2.3 ▲▲▲ | 26.7±15.8 ▲▲▲ |
| The ease pill group | 6 | 10 | 13.4±7.2*** | 48.8±21.6* |
| The Yueju Wan group | 6 | 10 | 9.1±4.4** | 49.8±18.0** |
| The YUEJU extractum group | 6 | 10 | 11.3±3.3*** | 50.1±14.6** |
| The YUEJU extractum group | 3 | 10 | 12.6±5.9*** | 48±22.5* |
| The YUEJU extractum group | 1.5 | 10 | 5.6±2.7 | 32.2±15.5 |
Annotate: 1. stagnation of liver-QI model group and normal control group are relatively
▲ ▲ ▲P＜0.001
2. each administration group and normal control group compare * P＜0.05 * * P＜0.01 * * * P＜0.001
Table 30 shows that die methods enrages the vertical movable and all significantly minimizings (P＜0.001) of horizontal anomalous movement of liver depression rat model.Compare with model group, YUEJU extractum 6 all can extremely significantly increase the vertical movable number of times of animal (P＜0.001) with 3g/kg dosage group, respectively can extremely remarkable and obvious increase animal horizontal anomalous movement number of times (P＜0.01 or P＜0.05).
Table 31 YUEJU extractum enrages the influence of liver depression rat model body weight gain to die methods
| Group | Dosage (g/kg) | Mus number (only) | Body weight (g) | Rate of increase (%) | |
| Before the modeling | Modeling and administration 18 days | ||||
| The normal control group | -- | 10 | 203±11.1 | 217.5±13.6 | 7.14±3.34 |
| Model group | -- | 10 | 204.4±12.9 | 203.5±13.0 ▲ | 0.52±3.32 ▲▲▲ |
| The ease pill group | 6 | 10 | 200.4±12.4 | 205.8±13.7 | 2.70±2.00 |
| The Yueju Wan group | 6 | 10 | 198.3±12.1 | 207.9±14.3 | 5.52±6.87* |
| The YUEJU extractum group | 6 | 10 | 198.9±11.2 | 205.7±12.6 | 3.43±2.57* |
| The YUEJU extractum group | 3 | 10 | 201.8±10.4 | 204.2±10.1 | 1.22±1.86 |
| The YUEJU extractum group | 1.5 | 10 | 202.9±13.3 | 203.6±13.6 | 0.36±2.06 |
Annotate: 1. stagnation of liver-QI model group and normal control group are relatively
▲P＜0.05
▲ ▲ ▲P＜0.001
2. each administration group and model group compare * P＜0.05
Table 31 shows that die methods enrages the liver depression rat model and rats in normal control group compares, and body weight gain extremely significantly reduces (P＜0.001).YUEJU extractum 6g/kg dosage group can obviously be resisted rat body weight and reduce (P＜0.05), 3 and 1.5g/kg dosage group the trend (P＞0.05 and P＞0.05) of antagonism is arranged.
Table 32 YUEJU extractum to die methods enrage liver depression rat model hemorheological property influence (
)
| Group | Dosage (g/kg) | Mus number (only) | Whole blood viscosity (mPaS) | Packed cell volume (%) | Erythrocyte aggregation index (Lb) | |
| 200 1/S | 1 1/S | |||||
| The normal control group | Distilled water | 10 | 4.51 ±0.64 | 27.91 ±6.30 | 39.7 ±2.50 | 6.53 ±0.64 |
| Model group | Distilled water | 10 | 5.70 ▲▲▲ ±0.57 | 45.81 ▲▲▲ ±6.13 | 40.9 ±2.85 | 8.43 ▲▲▲ ±0.66 |
| The ease pill group | 6 | 10 | 4.59*** ±0.38 | 28.86** ±5.36 | 44.8** ±2.85 | 6.70*** ±0.76 |
| The Yueju Wan group | 4 | 10 | 5.31 ±0.78 | 32.40 ±7.09 | 41.90 ±5.86 | 6.00 ±0.96 |
| The YUEJU extractum group | 4 | 10 | 5.42 ±0.89 | 30.65 ±8.89 | 41.50 ±3.95 | 5.98*** ±0.98 |
| 2 | 10 | 4.93** ±0.43 | 25.88*** ±6.09 | 43.20 ±0.024 | 5.70*** ±1.21 | |
| 1 | 10 | 4.96*** ±0.62 | 29.10*** ±4.69 | 43.70 ±2.67 | 6.75*** ±0.62 | |
Annotate: 1. model group matched group and normal control group are relatively
▲ ▲ ▲P＜0.001
2. each administration group and model group compare * P＜0.05 * * P＜0.01 * * * P＜0.001
Table 32 shows that die methods enrages liver depression rat model whole blood viscosity (Gao Qie and low cutting) and all extremely significantly risings (P＜0.001) of erythrocyte aggregation index.YUEJU extractum 3 and 1.5g/kg dosage group respectively can be significantly or are extremely significantly suppressed the rising (P＜0.001 or P＜0.01) of whole blood viscosity (Gao Qie and low cutting), and compare no difference of science of statistics (P＞0.05) with the normal control group; YUEJU extractum 6,3 and 1.5g/kg dosage group all can the extremely significantly exponential risings of inhibiting erythrocyte aggregation (P＜0.001).
Table 33 YUEJU extractum enrages the influence of monoamine neurotransmitter and metabolite content in the liver depression rat model brain to die methods
Annotate: 1. model group and normal control group are relatively
▲P＜0.05
▲ ▲P＜0.01
2. each administration group and model group compare * P＜0.05 * * P＜0.01 * * * P＜0.001
Table 33 result demonstration, die methods enrage the liver depression rat model and control rats compares, extremely remarkable, obvious, the remarkable and significantly reduction (P＜0.001, P＜0.05, P＜0.01 and P＜0.01) of DOPAC, NE, 5-HT and 5-HIAA content difference in the brain.YUEJU extractum 6g/kg dosage group respectively can the interior dopamine (DA) of obvious and remarkable elevation model animal brain and the content (P＜0.05 and P＜0.01) of 5-hydroxyindole (5-HIAA) after 18 days for successive administration.
Embodiment 1:The preparation of YUEJU JIAONANG agent
Get Rhizoma Cyperi (vinegar system) 400g, Rhizoma Chuanxiong 400g, Rhizoma Atractylodis (stir-fry) 400g, Fructus Gardeniae (parched) 400g, Massa Medicata Fermentata (stir-fry) 400g, beta-schardinger dextrin-110g, starch 110g, micropowder silica gel 5g, more than prescription is made 1000 of YUEJU JIAONANG, every encapsulated content 0.5g.
Embodiment 2:The preparation method of YUEJU JIAONANG agent
Rhizoma Cyperi (processed with vinegar), Fructus Gardeniae (parched), Rhizoma Atractylodis (parched), Rhizoma Chuanxiong, the stir-fry Massa Medicata Fermentata five tastes medicine of getting equivalent feed intake with decoction pieces, add 3.5 times of water gagings and soak into after 1 hour, add 9 times of water gagings and extract volatile oil 7 hours; Filtering residue adds 10 times of water gagings and decocts each 2 hours 2 times; Water extract filtrate is concentrated into relative density is 1.15 ± 0.02 under 60 ℃ of conditions, adds 80% ethanol of 8 times of extractum amounts, stir, left standstill 20 hours, filter, filtering residue discards, and reclaims ethanol, concentrates, and 45 ℃ of drying under reduced pressure of thick paste are pulverized, extract powder; Volatile oil beta-cyclodextrin inclusion compound, the rate of charge of volatile oil and beta-schardinger dextrin-are 1: 10, and 50 ℃ of following insulated and stirred, mixing speed are 1000rpm, and mixing time is 2 hours; Extract powder adds beta-schardinger dextrin-and starch by 2: 1: 2, the alcohol granulation with 90%, 50 ℃ of dryings, be 2 o'clock drying time, the selection consumption be 1.5% micropowder silica gel as lubricant, the Capsules of packing into is made capsule, promptly;
Embodiment 3:
Rhizoma Cyperi (processed with vinegar), Fructus Gardeniae (parched), Rhizoma Atractylodis (parched), Rhizoma Chuanxiong, the stir-fry Massa Medicata Fermentata five tastes medicine of getting equivalent feed intake with decoction pieces, add 3 times of above water infiltrations of amount after 1 hour, add 10 times of water gagings and extract volatile oil 6 hours, and filtering residue adds 8 times of water gagings and decocts each 1 hour 2 times; Water extract filtrate is concentrated into relative density is 1.15 under 60 ℃ of conditions, adds 90% ethanol of 4 times of extractum amounts, stir, left standstill 12 hours, filter, filtering residue discards, and reclaims ethanol, concentrates, and 40 ℃ of drying under reduced pressure of thick paste are pulverized; Volatile oil beta-cyclodextrin inclusion compound, the ingredient proportion of volatile oil and beta-schardinger dextrin-are 1: 10, and 60 ℃ of following insulated and stirred, mixing speed are 1200rpm, and mixing time is 3 hours; Extract powder adds beta-schardinger dextrin-and starch by 2: 1: 1, the alcohol granulation with 90%, 50 ℃ of dryings, be 1.5 hours drying time, the selection consumption be 1.5% micropowder silica gel as lubricant, the Capsules of packing into is made capsule, promptly;
Embodiment 4:Jasminoidin assay in the test agent in three batches:
Get in three batches trial production, jasminoidin content is measured, the every batch of parallel assay 3 times the results are shown in Table 34.
Jasminoidin assay table 34 as a result in table 34 sample
| Batch | Measurement result (mg/ grain) | On average (mg/ grain) |
| 020310 | 5.95 5.95 5.94 | 5.95 |
| 020311 | 5.90 5.91 5.90 | 5.90 |
| 020312 | 5.87 5.88 5.88 | 5.88 |
According to three batch sample measurement results, every contains the jasminoidin meter and is no less than 5.80mg.
Embodiment 4:The qualitative identification of Fructus Gardeniae
Get and bring up composite preparation capsule 's content 2g more, porphyrize adds methanol 20ml, and supersound process 30 minutes filters, and filtrate is concentrated into dried, adds methanol 1ml and makes dissolving, as need testing solution.Other gets Fructus Gardeniae control medicinal material 1g, shines medical material solution in pairs with legal system; Draw above-mentioned two kinds of each 10ul of solution, put respectively on same silica gel g thin-layer plate, with 5: 3: 1: 1 ethyl acetate-acetone-formic acid-water is developing solvent, launches, takes out, dries; Spray is with 10% ethanol solution of sulfuric acid, and hot blast blows to speckle and develops the color; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color; The negative control product then do not have this speckle;
Embodiment 5:
Get YUEJU JIAONANG 4g, porphyrize, the 30ml that adds diethyl ether, reflux 1 hour is put coldly, filters, and filtrate volatilizes ether, and residue adds ethyl acetate 1ml dissolving as need testing solution; Get scarce Rhizoma Atractylodis negative sample 4g, make negative sample solution with method; Other gets Rhizoma Atractylodis control medicinal material 1g, shines medical material liquid in pairs with legal system; Getting above-mentioned three kinds of each 10ul of solution, put respectively on same silica gel g thin-layer plate, is developing solvent with 70 ℃ of petroleum ether, launches, and taking-up is dried, and spray is with 10% ethanol solution of sulfuric acid of 5% paradime thylaminobenzaldehyde, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the speckle of same color, negative sample does not then have this speckle;
Embodiment 6:
Get YUEJU JIAONANG 4g, porphyrize adds ethyl acetate 15ml, and supersound process 20 minutes filters, and filtrate is concentrated into 1ml as need testing solution; Get scarce Rhizoma Chuanxiong negative sample 4g, make negative sample solution with method; Rhizoma Chuanxiong control medicinal material 1g makes reference substance solution with method in addition; Getting above-mentioned three kinds of each 10ul of solution, put respectively on same silica gel g thin-layer plate, is developing solvent with 9: 1 normal hexane-ethyl acetates, launches, and taking-up is dried; Put under the 365nm uviol lamp and inspect; In the test sample chromatograph, showing the fluorescence speckle of same color with the corresponding position of reference substance chromatograph, negative sample does not then have this speckle;
Embodiment 7:
Get YUEJU JIAONANG 3g, porphyrize, the 20ml that adds diethyl ether, supersound process filtered after 20 minutes, and filtrate simmer down to 1ml is as need testing solution; Get scarce Rhizoma Cyperi negative sample 3g, make negative sample solution with method; Other gets the Rhizoma Cyperi control medicinal material, shines medical material solution in pairs with legal system; Drawing above-mentioned three kinds of each 10ul of solution and put respectively on same silica gel g thin-layer plate, is developing solvent with 1: 5.5 ethyl acetate-petroleum ether, launches, and takes out, and dries; Spray is with 5% phosphomolybdic acid-alcoholic solution, 105 ℃ dry by the fire to the speckle colour developing clear; In the test sample chromatograph, showing the speckle of same color in corresponding position with the control medicinal material chromatograph, negative sample does not then have this speckle;
Embodiment 8:The application 1 of YUEJU JIAONANG agent
Get Rhizoma Cyperi (vinegar system) 400g, Rhizoma Chuanxiong 400g, Rhizoma Atractylodis (stir-fry) 400g, Fructus Gardeniae (stir-fry) 400g, Massa Medicata Fermentata (stir-fry) 400g, beta-schardinger dextrin-110g, starch 110g, micropowder silica gel 5g, more than prescription is made 1000 of YUEJU JIAONANG, is used for depression.Oral, one time 3,3 times on the one.
Embodiment 9:The application 2 of YUEJU JIAONANG agent
Get Rhizoma Cyperi (vinegar system) 400g, Rhizoma Chuanxiong 400g, Rhizoma Atractylodis (stir-fry) 400g, Fructus Gardeniae (stir-fry) 400g, Massa Medicata Fermentata (stir-fry) 400g, beta-schardinger dextrin-110g, starch 110g, micropowder silica gel 5g, more than prescription is made 1000 of YUEJU JIAONANG, is used to occur the patients with depression of blepharoptosis, myasthenia of limbs, symptom such as tired, drowsiness.Oral, one time 3,3 times on the one.
Embodiment 10:The application 3 of YUEJU JIAONANG agent
Get Rhizoma Cyperi (vinegar system) 400g, Rhizoma Chuanxiong 400g, Rhizoma Atractylodis (stir-fry) 400g, Fructus Gardeniae (stir-fry) 400g, Massa Medicata Fermentata (stir-fry) 400g, beta-schardinger dextrin-110g, starch 110g, micropowder silica gel 5g, more than prescription is made 1000 of YUEJU JIAONANG, be used to occur bradykinesia, motion can not, dysthymic patients with depression.Oral, one time 3,3 times on the one.
Embodiment 11:The application 4 of YUEJU JIAONANG agent
Get Rhizoma Cyperi (vinegar system) 400g, Rhizoma Chuanxiong 400g, Rhizoma Atractylodis (stir-fry) 400g, Fructus Gardeniae (stir-fry) 400g, Massa Medicata Fermentata (stir-fry) 400g, beta-schardinger dextrin-110g, starch 110g, micropowder silica gel 5g, more than prescription is made 1000 of YUEJU JIAONANG, is used for the stagnation of liver-QI patient.Oral, one time 3,3 times on the one.
Claims (11)
1, a kind of Chinese medicinal capsule for the treatment of depression is characterized in that it is made by following method:
Rhizoma Cyperi (processed with vinegar), Fructus Gardeniae (parched), Rhizoma Atractylodis (parched), Rhizoma Chuanxiong, the stir-fry Massa Medicata Fermentata five tastes medicine of getting equivalent feed intake with decoction pieces, add 3～4 times of water gagings and soak into after 1 hour, add 8～10 times of water gagings and extract volatile oil 6～8 hours; Filtering residue adds 8～12 times of water gagings and decocts 1-3 time, each 1-3 hour; Water extract filtrate is concentrated into relative density is 1.15 ± 0.02 under 60 ℃ of conditions, adds the 70-90% ethanol of 4～10 times of extractum amounts, stir, left standstill 8-24 hour, filter, filtering residue discards, and reclaims ethanol, concentrates, 40～50 ℃ of drying under reduced pressure of thick paste are pulverized, and get extract powder; Volatile oil beta-cyclodextrin inclusion compound, the rate of charge of volatile oil and beta-schardinger dextrin-are 1: 8-12, and 40～60 ℃ of following insulated and stirred, mixing speed are 400～1200rpm, mixing time is 1～3 hour; Extract powder adds beta-schardinger dextrin-and starch by 2: 1: 1～3, the alcohol granulation with 90%, 50 ℃ of dryings, be 1.5-2.5 hour drying time, the selection consumption be 1.5% micropowder silica gel as lubricant, the Capsules of packing into is made capsule, promptly.
2, Chinese medicinal capsule as claimed in claim 1 is characterized in that it is made by following method:
Rhizoma Cyperi (processed with vinegar), Fructus Gardeniae (parched), Rhizoma Atractylodis (parched), Rhizoma Chuanxiong, the stir-fry Massa Medicata Fermentata five tastes medicine of getting equivalent feed intake with decoction pieces, add 3 times of water gagings and soak into after 1 hour, add 10 times of water gagings and extract volatile oil 6 hours, and filtering residue adds 8 times of water gagings and decocts each 1 hour 2 times; Water extract filtrate is concentrated into relative density is 1.15 under 60 ℃ of conditions, adds 90% ethanol of 4 times of extractum amounts, stir, left standstill 12 hours, filter, filtering residue discards, and reclaims ethanol, concentrates, and 40 ℃ of drying under reduced pressure of thick paste are pulverized; Volatile oil beta-cyclodextrin inclusion compound, the ingredient proportion of volatile oil and beta-schardinger dextrin-are 1: 10, and 60 ℃ of following insulated and stirred, mixing speed are 1200rpm, and mixing time is 3 hours; Extract powder adds beta-schardinger dextrin-and starch by 2: 1: 1, the alcohol granulation with 90%, 50 ℃ of dryings, be 1.5 hours drying time, the selection consumption be 1.5% micropowder silica gel as lubricant, the Capsules of packing into is made capsule, promptly.
3, the discrimination method of Chinese medicinal capsule as claimed in claim 1 or 2 is characterized in that it comprises in the following method one or more:
A, get and bring up composite preparation capsule 's content 2g more, porphyrize adds methanol 15～30ml supersound process 20～40 minutes, filters, and filtrate is concentrated into dried, adds methanol 1ml and makes dissolving, as need testing solution; Other gets Fructus Gardeniae control medicinal material 1g, shines medical material solution in pairs with legal system; Get molten and each 10ul of control medicinal material solution of test sample, put respectively on same silica gel g thin-layer plate, with 4～6: 2.5～3.5: the ethyl acetate-acetone of 1: 1 ratio-formic acid-water is developing solvent, launches, takes out, dries; Spray is with 5～15% ethanol solution of sulfuric acid, and hot blast blows to speckle and develops the color; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
B, get and bring up composite preparation capsule 's content 3g more, porphyrize, the 20～40ml that adds diethyl ether, reflux 1～1.5 hour is put coldly, filters, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, as need testing solution; Other gets Rhizoma Atractylodis control medicinal material 1g, shines medical material solution in pairs with legal system; Getting need testing solution and each 10ul of control medicinal material solution, put respectively on same silica gel g thin-layer plate, is developing solvent with 60～90 ℃ of petroleum ether, launch, take out, dry, spray is with 8～12% ethanol solution of sulfuric acid of 4～6% paradime thylaminobenzaldehydes, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the speckle of same color;
C, get and bring up composite preparation capsule 's content 3g more, porphyrize, the 15～30ml that adds diethyl ether, supersound process 15～30 minutes filters, and filtrate simmer down to 1ml is as need testing solution; Other gets Rhizoma Cyperi control medicinal material 1g, shines medical material solution in pairs with legal system; Drawing need testing solution and each 10ul of control medicinal material solution, put respectively on same silica gel g thin-layer plate, is developing solvent with the ethyl acetate-petroleum ether of 1: 5～6 ratios, launches, and takes out, and dries; Spray is with 4～6% phosphomolybdic acid-alcoholic solution, and 105～110 ℃ to be heated to the speckle colour developing clear; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph, show the speckle of same color;
D, get and bring up composite preparation capsule 's content 4g more, porphyrize adds ethyl acetate 10～20ml, and supersound process 15～30 minutes filters, and filtrate is concentrated into 1ml as need testing solution; Other gets Rhizoma Chuanxiong control medicinal material 1g, shines medical material solution in pairs with legal system; Get need testing solution and each 10ul of control medicinal material solution, put respectively on same silica gel g thin-layer plate, with 8～10: the n-hexane-ethyl acetate of 1 ratio is developing solvent, launches, and taking-up is dried; Put under the 365nm uviol lamp and inspect; In the test sample chromatograph, showing the fluorescence speckle of same color with the corresponding position of reference substance chromatograph.
4, discrimination method as claimed in claim 3 is characterized in that this method comprises one or more in the following method:
A, get and bring up composite preparation capsule 's content 2g more, porphyrize adds methanol 20ml, and supersound process 30 minutes filters, and filtrate is concentrated into dried, adds methanol 1ml and makes dissolving, as need testing solution; Other gets Fructus Gardeniae control medicinal material 1g, shines medical material solution in pairs with legal system; Draw need testing solution and each 10ul of control medicinal material solution, put respectively on same silica gel g thin-layer plate, with 5: 3: 1: the ethyl acetate-acetone of 1 ratio-formic acid-water is developing solvent, launches, and takes out, and dries; Spray is with 10% ethanol solution of sulfuric acid, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
B, get and bring up composite preparation capsule 's content 3g more, porphyrize, the 30ml that adds diethyl ether, reflux 1 hour is put coldly, filters, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, as need testing solution; Other gets Rhizoma Atractylodis control medicinal material 1g, shines medical material solution in pairs with legal system; Drawing need testing solution and each 10ul of control medicinal material solution, put respectively on same silica gel g thin-layer plate, is developing solvent with 60～90 ℃ of petroleum ether, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid of 5% paradime thylaminobenzaldehyde, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
C, get and bring up composite preparation capsule 's content 3g more, porphyrize, the 20ml that adds diethyl ether, supersound process 20 minutes filters, and filtrate simmer down to 1ml is as need testing solution; Other gets Rhizoma Cyperi control medicinal material 1g, shines medical material solution in pairs with legal system; Drawing need testing solution and each 10ul of control medicinal material solution, put respectively on same silica gel g thin-layer plate, is developing solvent with the ethyl acetate-petroleum ether of 1: 5.5 ratio, launches, and takes out, and dries; Spray is with 5% phosphomolybdic acid ethanol solution, and it is clear to be heated to the speckle colour developing at 105 ℃; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
D, get and bring up composite preparation capsule 's content 4g more, porphyrize adds ethyl acetate 20ml, and supersound process 20 minutes filters, and filtrate is concentrated into 1ml, as need testing solution; Other gets Rhizoma Chuanxiong control medicinal material 1g, shines medical material solution in pairs with legal system; Drawing need testing solution and each 10ul of control medicinal material solution, put respectively on same silica gel g thin-layer plate, is developing solvent with the normal hexane-ethyl acetate of 9: 1 ratios, launches, and taking-up is dried, and puts under the 365nm ultra-violet lamp and inspects; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the fluorescence speckle of same color.
5, the content assaying method of Chinese medicinal capsule as claimed in claim 1 or 2 is characterized in that this method comprises following assay method:
Chromatographic condition: with octadecylsilane chemically bonded silica is filler; 10～20: 80～90 acetonitrile-waters are mobile phase; Flow velocity: 1.0mlmin
-1Detect wavelength: 238nm; Column temperature: 35 ℃; The external standard method peak area quantification;
Reference substance solution preparation: take by weighing at 3～5 hours jasminoidin reference substance of 60 ℃ of drying under reduced pressure, add methanol and make solution that every 1ml contains 30ug promptly;
The need testing solution preparation: the extract powder 0.1g of the compositions of getting it filled, it is fixed to claim after the constant weight, puts in the 25ml volumetric flask to add methanol to scale, supersound process 20～40 minutes, put coldly, supply volume, shake up with methanol, filter, precision is measured subsequent filtrate 5ml, puts in the 10ml volumetric flask, adds methanol to scale, shake up, promptly;
Algoscopy: draw each 10ul of reference substance solution and need testing solution respectively, inject chromatograph of liquid, measure, promptly;
Every of the capsule of this pharmaceutical composition contains the jasminoidin meter must not be less than 4.50～6.00mg.
6, content assaying method as claimed in claim 5 is characterized in that this method comprises following assay method:
Chromatographic condition: with octadecylsilane chemically bonded silica is filler; 15: 85 acetonitrile-waters are mobile phase; Flow velocity: 1.0mlmin
-1Detect wavelength: 238nm; Column temperature: 35 ℃; The external standard method peak area quantification;
Reference substance solution preparation: take by weighing at 4 hours jasminoidin reference substance of 60 ℃ of drying under reduced pressure, add methanol and make solution that every 1ml contains 30ug promptly;
The need testing solution preparation: the extract powder 0.1g of the compositions of getting it filled, it is fixed to claim after the constant weight, puts in the 25ml volumetric flask to add methanol to scale, supersound process 20 minutes, put coldly, supply volume, shake up with methanol, filter, precision is measured subsequent filtrate 5ml, puts in the 10ml volumetric flask, adds methanol to scale, shake up, promptly;
Algoscopy: draw each 10ul of reference substance solution and need testing solution respectively, inject chromatograph of liquid, measure, promptly;
Every of capsule of the present invention contains the jasminoidin meter must not be less than 4.5mg.
7,, it is characterized in that wherein methanol can be substituted by 70% ethanol or ethyl acetate as claim 5 or 6 described content assaying methods.
8,, it is characterized in that ultrasonic processing method wherein can be substituted by the water-bath reflow method as claim 5 or 6 described content assaying methods.
9,, it is characterized in that wherein acetonitrile-water mobile phase can be substituted by acetonitrile-0.1% phosphoric acid solution mobile phase as claim 5 or 6 described content assaying methods.
10, a kind of preparation method for the treatment of the Chinese medicinal capsule of depression is characterized in that this method is:
Rhizoma Cyperi (processed with vinegar), Fructus Gardeniae (parched), Rhizoma Atractylodis (parched), Rhizoma Chuanxiong, the stir-fry Massa Medicata Fermentata five tastes medicine of getting equivalent feed intake with decoction pieces, add 3～4 times of water gagings and soak into after 1 hour, add 8～10 times of water gagings and extract volatile oil 6～8 hours; Filtering residue adds 8～12 times of water gagings and decocts 1-3 time, each 1-3 hour; Water extract filtrate is concentrated into relative density is 1.15 ± 0.02 under 60 ℃ of conditions, adds the 70-90% ethanol of 4～10 times of extractum amounts, stir, left standstill 8-24 hour, filter, filtering residue discards, and reclaims ethanol, concentrates, 40～50 ℃ of drying under reduced pressure of thick paste are pulverized, and get extract powder; Volatile oil beta-cyclodextrin inclusion compound, the rate of charge of volatile oil and beta-schardinger dextrin-are 1: 8-12, and 40～60 ℃ of following insulated and stirred, mixing speed are 400～1200rpm, mixing time is 1～3 hour; Extract powder adds beta-schardinger dextrin-and starch by 2: 1: 1～3, the alcohol granulation with 90%, 50 ℃ of dryings, be 1.5-2.5 hour drying time, the selection consumption be 1.5% micropowder silica gel as lubricant, the Capsules of packing into is made capsule, promptly.
11, preparation method as claimed in claim 10 is characterized in that this method is:
Rhizoma Cyperi (processed with vinegar), Fructus Gardeniae (parched), Rhizoma Atractylodis (parched), Rhizoma Chuanxiong, the stir-fry Massa Medicata Fermentata five tastes medicine of getting equivalent feed intake with decoction pieces, add 3 times of water gagings and soak into after 1 hour, add 10 times of water gagings and extract volatile oil 6 hours, and filtering residue adds 8 times of water gagings and decocts each 1 hour 2 times; Water extract filtrate is concentrated into relative density is 1.15 under 60 ℃ of conditions, adds 90% ethanol of 4 times of extractum amounts, stir, left standstill 12 hours, filter, filtering residue discards, and reclaims ethanol, concentrates, and 40 ℃ of drying under reduced pressure of thick paste are pulverized; Volatile oil beta-cyclodextrin inclusion compound, the ingredient proportion of volatile oil and beta-schardinger dextrin-are 1: 10, and 60 ℃ of following insulated and stirred, mixing speed are 1200rpm, and mixing time is 3 hours; Extract powder adds beta-schardinger dextrin-and starch by 2: 1: 1, the alcohol granulation with 90%, 50 ℃ of dryings, be 1.5 hours drying time, the selection consumption be 1.5% micropowder silica gel as lubricant, the Capsules of packing into is made capsule, promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100701262A CN1332690C (en) | 2004-08-02 | 2004-08-02 | Technique for preparing Yueju capsule and quality control method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100701262A CN1332690C (en) | 2004-08-02 | 2004-08-02 | Technique for preparing Yueju capsule and quality control method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1733189A CN1733189A (en) | 2006-02-15 |
| CN1332690C true CN1332690C (en) | 2007-08-22 |
Family
ID=36075944
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004100701262A Expired - Fee Related CN1332690C (en) | 2004-08-02 | 2004-08-02 | Technique for preparing Yueju capsule and quality control method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1332690C (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103134883B (en) * | 2011-11-28 | 2015-05-13 | 邯郸制药股份有限公司 | Medicine composition and detecting method of formula of medicine composition |
| CN105548452A (en) * | 2016-02-05 | 2016-05-04 | 四川德成动物保健品有限公司 | Thin-layer chromatography detection method of cape jasmines in heat-clearing and detoxifying powder |
| CN110873776B (en) * | 2018-08-30 | 2022-04-05 | 四川新绿色药业科技发展有限公司 | Identification method of gardenia and fried gardenia formula granules |
| CN114099479A (en) * | 2021-12-24 | 2022-03-01 | 江苏七○七天然制药有限公司 | A Chinese medicinal cataplasma for treating depression by acupoint application, and its preparation method |
-
2004
- 2004-08-02 CN CNB2004100701262A patent/CN1332690C/en not_active Expired - Fee Related
Non-Patent Citations (5)
| Title |
|---|
| 中医证型与血液流变学相关性研究 侯淑英等，微循环技术杂志，第4期 1994 * |
| 抑郁症单胺类递质受体研究进展 高霄飞等，生理科学进展，第33卷第1期 2002 * |
| 抑郁症单胺类递质受体研究进展 高霄飞等，生理科学进展，第33卷第1期 2002;越鞠胶囊中香附、栀子TLC鉴别和栀子苷含量测定研究 袁丹等，药物分析杂志，第23卷第4期 2003;越鞠汤治疗缺血性中风后抑郁症临床观察 李宝玲等，山西中医，第19卷第1期 2003;中医证型与血液流变学相关性研究 侯淑英等，微循环技术杂志，第4期 1994 * |
| 越鞠汤治疗缺血性中风后抑郁症临床观察 李宝玲等，山西中医，第19卷第1期 2003 * |
| 越鞠胶囊中香附、栀子TLC鉴别和栀子苷含量测定研究 袁丹等，药物分析杂志，第23卷第4期 2003 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1733189A (en) | 2006-02-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1899361B (en) | Zhenqi medicinal composition and its preparation | |
| CN101961422B (en) | Extractive of Pu'er tea and preparation method thereof | |
| CN103381217B (en) | A kind of Liuweibuxue capsule and method of quality control thereof and application | |
| CN100525809C (en) | Medicinal composition of milkvetch root, chinaroot greenbrier and Hong Jingtian and its making method | |
| CN102120015A (en) | Traditional Chinese medicine for soothing liver and dispersing depressed vital energy and soothing nerves and sedating mind, and preparation method and quality standard thereof | |
| CN114081906B (en) | Traditional Chinese medicine composition for treating constipation and preparation method thereof | |
| CN100534456C (en) | Milkwort extract, its preparation method and usage | |
| CN108014150A (en) | Application of the natural drug composition in anti anoxia and radiation-resistant medicine or food is prepared | |
| CN1332690C (en) | Technique for preparing Yueju capsule and quality control method | |
| CN102114060A (en) | Amur valeriana extract and preparation method and applications thereof | |
| CN103550398B (en) | Composition for relieving fatigue as well as preparation method and medical application thereof | |
| CN107569612A (en) | A kind of medicine for improving sleep and preparation method thereof | |
| CN103735712B (en) | Preparation method of Chinese medicinal composition and Chinese medicinal composition prepared by using preparation method | |
| CN105616960A (en) | Traditional Chinese medicine composition with anti-anemia effect as well as preparation method and application thereof | |
| CN105031005A (en) | Micro pills capable of tonifying qi and benefiting blood | |
| CN101411758B (en) | Chinese medicine solid formulation for treating insomnia and preparation method thereof | |
| CN101461898B (en) | Chinese medicine solid preparation for treating climacteric syndrome and preparation method thereof | |
| CN101856489B (en) | Swine health granules and preparation process thereof | |
| CN100427076C (en) | Medicinal preparation for treating embolus and its preparation method | |
| CN102488722A (en) | Preparation method and quality detection method of bupleurum oral solution | |
| CN102836334B (en) | Veterinary Chinese medicinal preparation for replenishing qi to invigorate spleen | |
| CN102048841A (en) | Lactogenic traditional Chinese medicine composition and preparation method thereof | |
| CN102048890A (en) | Traditional Chinese medicine composition with galactagogue effect and preparation method thereof | |
| CN101564465A (en) | Chinese medicinal composition for nourishing blood, benefiting vital energy, regulating menstruation and dissipating cold | |
| CN104352940B (en) | A kind of Chinese medicine composition for alleviating physical fatigue |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20070822 Termination date: 20100802 |