CN105535271A - Girald daphne bark tablets for treating scapulohumeral periarthritis and nursing auxiliary medicine thereof for treating epilepsy - Google Patents
Girald daphne bark tablets for treating scapulohumeral periarthritis and nursing auxiliary medicine thereof for treating epilepsy Download PDFInfo
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/83—Thymelaeaceae (Mezereum family), e.g. leatherwood or false ohelo
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention relates to the field of traditional Chinese medicines, and in particular relates to girald daphne bark tablets for treating scapulohumeral periarthritis and a nursing auxiliary medicine thereof for treating epilepsy. The tablets are prepared from the following raw materials by the steps of: taking girald daphne barks, and adding water for decocting for three times, 2 hours for the first time, and 1 hour for each of the second time and the third time; combining decoction solutions, filtering, and concentrating the filtrate until the relative density is 1.22-1.26 to obtain a clear paste; adding ethanol to ensure that the alcohol content reaches 75%; standing for deposition; taking a supernatant; recovering the ethanol and carrying out concentration; adding calcium carbonate, starch, and dextrin, and mixing uniformly to prepare granules; and drying, pressing into tablets, and coating with film coatings or sugar coatings to obtain the girald daphne bark tablets. The medicine is used for preparing medicines or health products for treating scapulohumeral periarthritis and epilepsy.
Description
Technical field
The present invention relates to the field of Chinese medicines, be specifically related to a kind of Giraldi daphne tablet and method for making thereof and novelty teabag.
Background technology
Daphne giraldii Nitsche is root bark and the peel of stem of thymelaeceae (Thymelaeaceae) daphne plant Daphne Giraldii Nitsche (DaphnegiraldiiNitsche).Giraldi daphne tablet is dampclearing prescription, has expelling wind and removing dampness, effect of promoting blood circulation and stopping pain.Cure mainly wind and cold to wet impatency, the numbness caused by obstruction of collaterals by blood stasis, disease sees that limbs joint swells and ache, aversion to cold and cold limbs; Rheumatoid scapulohumeral periarthritis is shown in above-mentioned patient.Be usually used in cure scapulohumeral periarthritis, rheumatoid scapulohumeral periarthritis; Also can be used for sciatica, scapulohumeral periarthritis.The drug standard of Giraldi daphne tablet records in version " Chinese Pharmacopoeia " the 1321st page in 2015.
Show in existing report, 2000, the people such as Yang Jianhui, Tu little Wen, Wang Yanxia are at " the 6th national combination of Chinese and Western medicine nephropathy academic meeting paper compilation " upper report, and Daphne giraldii Nitsche may be used for treating glomerulonephritis.2008, the people such as Lin Zhixiang, Zheng Liangcheng, Dai Yichen, Dai Lushou, Zhou Mingxuan were at " Hainan medical science " upper report, and Giraldi daphne tablet can be used for treatment rheumatoid scapulohumeral periarthritis.2009, Chen Jianle reported in Master degree candidate's thesis of its Colleges Of Traditional Chinese Medicine Of Fujian, and Giraldi daphne tablet can treat senile knee joint scapulohumeral periarthritis.2013, the people such as Guo Xingfu, Wu Lijuan, Yu Jinyun, Song Yuping were at " practical Chinese medicine magazine " upper report, and Giraldi daphne tablet can treat acute low back pain.Chinese patent CN201310600707.1 discloses a kind of Chinese medicine for the treatment of gastric cancer of spleen-stomach deficiency and preparation method thereof, and each raw medicinal material of Chinese medicine comprises: cold syndrome of the stomach grass, Herba Thymi, Semen Sinapis Albae, Daphne giraldii Nitsche, Radix Pimpinellae Candolleanae, great Ye Cortex cinnamomi japonici (Ramulus Cinnamomi), Alpinia henryik Schum, Radix Crotonis, Fructus Evodiae Meliifoliae, Radix Inulae, Semen Alpiniae Katsumadai, Fructus Gomphocarpi futicosi and Semen Firmianae, Chinese medicine warming spleen and stomach for dispelling cold of the present invention, invigorating the spleen and regulating the stomach, significantly can improve the symptom of gastric cancer of spleen-stomach deficiency patient.Disclose one in Chinese patent CN201310714450.2 and treat migrainous Chinese medicine preparation of obstruction of collaterals by blood stasis type and preparation method thereof, each raw medicinal material of Chinese medicine preparation comprises: Radix Ilicis Asprellae, Herba rhynchosiae volubilis, Rabdosia rubescens, Radix Dendropanacis, Herba Ocimi (Herba Ocimi Pilosi), Radix Rauvolfiae, Radix Solani indici, Herba Cymbopogonis Citrari, Caulis et Folium Desmodii Gangetici, Daphne giraldii Nitsche, the Herba Blumeae Laciniatae, Herba leerisae hexandrae, Bai Guimu root and Radix Parthenocissi Heterophyllae, Chinese medicine preparation blood circulation promoting and blood stasis dispelling of the present invention, removing obstruction in the collateral to relieve pain, has definite curative effect to obstruction of collaterals by blood stasis type migraine.Disclose a kind of Chinese medicine composition with antitumor action and its preparation method and application in Chinese patent CN201010195115.2, this Chinese medicine composition is made up of the raw material of following parts by weight: Rhizoma Chuanxiong 10 ~ 100 parts, Rhizoma Corydalis Decumbentis 10 ~ 200 parts, Radix Aconiti Preparata 1 ~ 50 part, Daphne giraldii Nitsche 10 ~ 300 parts, Radix Gentianae Macrophyllae 10 ~ 100 parts, Venenum Bufonis 1 ~ 50 part; Chinese medicine composition provided by the invention has the growth of good inhibition tumor cell and can promote the effect of apoptosis of tumor cells, and all has stronger killing action to kinds of tumor cells.Chinese invention patent CN201310299158.9 discloses a kind of Chinese medicine preparation for adjuvant therapy of depression and preparation method, and the constitutive material of this Chinese medicine preparation effective ingredient is Radix Cynanchi Auriculati, Succus Bambusae, Herba Orobanches, Herba Ixeritis chinensis, jasmine, Radix Ginseng Rubra, Cor Vulpes, Rhizoma Gastrodiae, Haematite, Radix Gentianae Macrophyllae, HANXIAOHUA, Radix Kansui, Folium Photiniae (Folium Photiniae serrulatae), Cortex Melaleucae leucadendrae, Radix Ariliae and Daphne giraldii Nitsche; Medicine of the present invention has dispersing the stagnated live-QI to relieve the stagnation of QI, nourishing blood to tranquillize the mind, calm tired effect of dispelling, and the neurasthenia caused because of the various cause of disease for auxiliary psychotherapy, schizophrenia, depression etc. have good effect.
Medicine provided by the invention may be used for cure scapulohumeral periarthritis and epilepsy.Show after deliberation, medicine of the present invention has good therapeutic effect to scapulohumeral periarthritis and epilepsy.
Summary of the invention
The object of this invention is to provide a kind of medicine of Giraldi daphne tablet.
Another object of the present invention is to provide the preparation method of this medicine.
Present invention also offers the new pharmaceutical use of this medicine.
The object of the invention is by realize with under type:
A medicine for Giraldi daphne tablet is be made up of following raw material: Daphne giraldii Nitsche.
This medicine is adopted and is prepared with the following method: get Daphne giraldii Nitsche, decoct with water three times, 2 hours first times, for the second time, third time 1 hour, collecting decoction, filter, filtrate is concentrated into the clear paste that relative density is 1.22 1.26, adds ethanol and makes alcohol content reach 75%, leaves standstill and makes precipitation, get supernatant, reclaim ethanol and concentrate, adding calcium carbonate, starch, dextrin, mixing, makes granule, dry, tabletted, film coating or sugar-coat, to obtain final product.
This medicine may be used for preparing cure scapulohumeral periarthritis, AED or health product.
Experiment one: the experimentation of medicine composite for curing epilepsy of the present invention
This research carries out experimentation by MES, pentylenetetrazole, strychinine-induced convulsion model to the antiepileptic action of pharmaceutical composition of the present invention.
1 materials and methods
1.1 medicine
Pharmaceutical composition of the present invention: prepare with reference to the embodiment 1 in description detailed description of the invention of the present invention.
1.2 animal Kunming mouses, weight 20 ~ 25g, male and female half and half.
1.3 reagent pentylenetetrazoles (Bo Hua bio tech ltd, Shanghai); Strychnine nitrate injection (Beijing Double-Crane Pharmaceutical Co., Ltd's production); Phenytoin sodium tablet (production of Shanghai Xin Pasi pharmaceutical Co. Ltd).
The 1.4 multiplex instrument of instrument YSD-4G pharmacology Physiological Experiment (Shanghai Tiancheng Technology Co., Ltd.).
1.5 method
1.5.1MES epilepsy mice adopts the multiplex instrument of YSD-4G pharmacology Physiological Experiment, after dentation folder is soaked with normal saline, clamp mice ears tip, preliminary experiment determines that the parameter of more than 95% animal generation tonic convulsion outbreak is 100V, 4Hz, stretch as convulsions index with hindlimb tonic, within first 1 day, screen in experiment.Get the Kunming mouse 30 meeting convulsions standard, be divided into 3 groups at random, be respectively: model control group, medicine group of the present invention, phenytoin Sodium group.By table 1 dosage gastric infusion, model control group such as to give at the molten long-pending distilled water, after administration 30min, by above-mentioned parameter, gives electricity irritation 1 time, calculates the number of elements of each group of mice against seizure.The results are shown in Table 1.
1.5.2 pentylenetetrazole epilepsy mice preliminary experiment determines that the pentylenetetrazole dosage that more than 95% animal occurs that paroxysmal is twitched is 92mg/kg.Mice 30, is divided into 3 groups at random, is respectively: model control group, medicine group of the present invention, phenytoin Sodium group.By table 2 dosage gastric infusion.Model control group gives isopyknic distilled water, 35min after administration, and lumbar injection is corresponding causes frightened dosage pentylenetetrazole, observes the anti-pentylenetetrazole of medicine and causes frightened curative effect, the results are shown in Table 2.
1.5.3 strychnine epilepsy mice preliminary experiment determines that the strychnine dosage that more than 95% animal occurs that paroxysmal is twitched is 0.7mg/kg.Get healthy mice 30, be divided into 3 groups at random, be respectively: model control group, medicine group of the present invention, phenytoin Sodium group.By table 3 dosage gastric infusion.Model control group gives isopyknic distilled water, 30min after administration, and subcutaneous injection is corresponding causes frightened dosage strychnine, observes the anti-strychnine of medicine and causes frightened curative effect.The results are shown in Table 3.
1.5.4 the grade scale of behavior observation epilepsy is with reference to Racine standard:
0 grade: reactionless;
I grade: rhythmicity mouth or face are twitched;
II grade: nod or whipping;
III grade: single limb is twitched;
IV grade: many limb twitches or tetanic;
V grade: comprehensive tetanic---grand mal.
Continuous Observation 40min, record mice epilepsy incubation period.
1.6 statistical procedures adopt SPSS13.0 statistical software to carry out analyzing and processing to above-mentioned observed result.Data metering data mean ± standard deviation (
± s) represent, the comparison of multisample mean and comparing between two with variance analysis test of mean, ranked data non parametric tests is analyzed.
2 results
2.1 pharmaceutical compositions of the present invention on the impact of epilepsy mice caused by MES in Table 1-1.
Table 1-1 is on the impact of mice convulsion incidence rate caused by MES
Note: compare with model group, #P<0.05, ##P<0.01.
2.2 pharmaceutical compositions of the present invention on the impact of pentylenetetrazole epilepsy mice in Table 1-2.
Table 1-2 on the impact of mice pentylenetetrazole convulsion model (
± s)
Note: compare with model group, #P<0.05, ##P<0.01.
2.3 pharmaceutical compositions of the present invention on the impact of strychnine epilepsy mice in Table 1-3.
Table 1-3 on the impact of mice strychinine-induced convulsion model (
± s)
Note: compare with model group, #P<0.05, ##P<0.01.
3 discuss and conclusion
This research select several epilepsy model never ipsilateral pharmaceutical composition antiepileptic action of the present invention is studied, find that pharmaceutical composition of the present invention can reduce MES attack times, extend pentylenetetrazole, strychnine induced mice faint from fear outbreak incubation period, improve epilepsy degree, and shorten the persistent period, point out medicine of the present invention to have certain therapeutical effect to epilepsy.
Experiment two: medicine high performance liquid chromatography quality determining method research of the present invention
1 instrument and reagent
1.1 instrument
High performance liquid chromatograph (Agilent110 high performance liquid chromatograph and work station, G1311Aquat pump, G1314 UV-detector).
1.2 reagent
Daphne Giraldii Nitsche glycosides B reference substance (Chinese pharmaceutical biological product calibrating academy); Chinese medicine composition of the present invention: prepare with reference to the embodiment 1 in description detailed description of the invention of the present invention; Chinese crude drug (Kang Ji chain pharmacy provides); Methanol (chromatograph alcohol, biochemical work auxiliary reagent factory, Shanghai); Other reagent are analytical pure.
2 methods and result
2.1 prescription
Daphne giraldii Nitsche 1100g
2.2 preparation
Get Daphne giraldii Nitsche, decoct with water three times, 2 hours first times, for the second time, third time 1 hour, collecting decoction, filter, filtrate is concentrated into the clear paste that relative density is 1.22 1.26, adds ethanol and makes alcohol content reach 75%, leaves standstill and makes precipitation, get supernatant, reclaim ethanol and concentrate, adding calcium carbonate, starch, dextrin, mixing, makes granule, dry, be pressed into 1000, film coating or sugar-coat, to obtain final product.
The assay of 2.3 Daphne Giraldii Nitsche glycosides B
2.3.1HPLC chromatographic condition
Adopt HypersilDs(4.0mm × 125mm, 5 μm) chromatographic column; Mobile phase: ratio is the acetonitrile-water of 30:70; Determined wavelength: 200nm; Column temperature: 20 DEG C; Flow velocity: 1.0mLmin
-1; Sample size: 10 μ L; Under this chromatographic condition, reference substance and sample chromatogram peak are well, noiseless to mensuration without Daphne giraldii Nitsche negative control.
2.3.2 the preparation of reference substance solution
It is appropriate that precision takes 80 DEG C of Daphne Giraldii Nitsche glycosides B reference substances being dried to constant weight, adds methanol and make the solution of every 1mL containing 0.2mg.
2.3.3 the preparation of need testing solution and negative controls
Precision takes medicine 10g of the present invention, adds methanol 40mL, reflux 4h, extracting solution reflux solvent is also concentrated into dry, residue add water 10mL dissolve, extract 5 times with water saturated n-butyl alcohol jolting, each 20mL, merges n-butanol extracting liquid, washs 3 times with ammonia solution, each 15mL, n-butanol extracting liquid recycling design is to dry, and residue adds dissolve with methanol and is transferred in 10mL volumetric flask, add methanol to scale, shake up, filter, get filtrate and get final product; Separately do not contain the negative controls of Daphne giraldii Nitsche in the preparation of prescription ratio, be made in the same way of negative controls.
2.3.4 the drafting of standard curve
It is appropriate that precision takes 80 DEG C of Daphne Giraldii Nitsche glycosides B reference substances being dried to constant weight, makes 10.4,20.8,41.6,83.2,166.4 μ gmL with methanol
-1the solution of series concentration, precision measures each 10 μ L of above-mentioned 5 kinds of strength solution respectively, injects high performance liquid chromatograph and measures.
Carry out linear regression with peak area ratio and concentration, obtaining regression equation is: A=21.2763C-0.1391, r=0.9999.Show that Daphne Giraldii Nitsche glycosides B is at 10.4 ~ 166.4 μ gmL
-1in good linear relationship in concentration range.
2.3.5 stability test
Accurate absorption need testing solution 10 μ L, respectively at 0,1,2,4,8h sample introduction, and calculates Daphne Giraldii Nitsche glycosides B content.In result 8h, RSD is 0.45%(n=5).Show that sample solution is stable in 8h.
2.3.6 replica test
By 5 parts, need testing solution preparation method parallel processing sample, measure Daphne Giraldii Nitsche glycosides B content in accordance with the law and calculate.It is 0.12mgmL that result records Daphne Giraldii Nitsche glycosides B average content
-1, RSD is 1.3%.
2.3.7 Precision Experiment
Accurate absorption Daphne Giraldii Nitsche glycosides B reference substance solution, repeats sample introduction 5 times, measures peak area in accordance with the law.Result RSD is 0.23%(n=5).Show that precision is better.
2.3.8 response rate experiment
Precision takes 6 parts, the sample of the same lot number of known Daphne Giraldii Nitsche glycosides B content, adds appropriate Daphne Giraldii Nitsche glycosides B reference substance solution, operate, measure in accordance with the law, calculate the response rate by under sample determination item by high, medium and low concentration is accurate respectively.Result average recovery rate is 100.3%, RSD is 0.45%(n=5).
2.3.9 sample size measures
Measure reference substance solution and need testing solution respectively appropriate, filter with microporous filter membrane, each sample introduction 10 μ L, measures 3 batch samples by above-mentioned chromatographic condition, parallel assay 5 times.By external standard method with the content of calculated by peak area need testing solution Daphne Giraldii Nitsche glycosides B.This product should be containing Daphne Giraldii Nitsche glycosides B and indicates 95% ~ 105% of content, in every 1g this product containing Daphne Giraldii Nitsche glycosides B, must not be less than 0.12mg.3 batch sample content are respectively 100.8%(RSD=1.2%), 101.7%(RSD=1.3%), 99.2%(RSD=1.1%).
Experiment three: the content of medicine air phase chromatography Simultaneous Determination isopulegol of the present invention, benzoaric acid
1 instrument and reagent
Agilent7890N gas chromatograph: fid detector, A.01.12.1 chromatographic work station; SGH-300 high-purity hydrogen generator (Beijing Orient elite science and technology garden Science and Technology Ltd.); Chromatographic column fused-silica capillary column (30m × 0.25mm, 0.25 μm); Prunus mume (sieb.) sieb.et zucc. Teller-Tuo benefit 100,000/electronic analytical balance; Isopulegol reference substance (content 99.9%, National Institute for Food and Drugs Control); Benzoaric acid reference substance (content 99.9%, National Institute for Food and Drugs Control); Medicine of the present invention (preparing with reference to the embodiment 1 in description detailed description of the invention of the present invention), reagent: Ketohexamethylene, dehydrated alcohol is chromatographically pure.
2 chromatographic conditions
Chromatographic column: ZB-WAX fused-silica capillary column (30m × 0.25mm, 0.25 μm); Carrier gas: N
2, 1.0mLmL
-1; Hydrogen, 40mLmL
-1; Air, 400mLmin
-1; Split ratio: 10:1; Injector temperature: 250 DEG C, detector temperature 300 DEG C; Temperature programming: initial 80 DEG C, 5 DEG C per minute rise to 120 DEG C, and 10 DEG C per minute rise to 180 DEG C, keep 3.5min; Internal standard method.
3 test methods and result
The preparation of 3.1 inner mark solutions
Get Ketohexamethylene appropriate, add anhydrous alcohol solution and dilute and make the solution of every 1g containing 12.5mg, shake up, as inner mark solution.
The preparation of 3.2 need testing solutions
Precision measures this product 1.0g, puts in 10mL volumetric flask, add dehydrated alcohol and be diluted to scale, then precision measures 1.0mL, and put in 10mL volumetric flask, precision adds inner mark solution 1.0mL, adds dehydrated alcohol and is diluted to scale, shake up.
The preparation of 3.3 reference substance stock solutions
Precision takes isopulegol reference substance, benzoaric acid reference substance is appropriate, adds anhydrous alcohol solution and dilute to make containing isopulegol 0.301mgmL
-1and benzoaric acid 0.901mgmL
-1reference substance stock solution, for subsequent use;
The preparation of 3.4 negative control solutions
Getting the blank solution by not adding isopulegol and benzoaric acid in prescription, by preparation method under " 3.2 " item, making negative control solution.
The investigation of 3.5 linear relationships
Respectively precision pipette 0.2,0.5,1.0,1.5,3.5mL reference substance storing solution is in 10mL volumetric flask, add inner mark solution 1.0mL, add dehydrated alcohol and be diluted to scale, shake up, product solution in contrast, get 1 μ L sample introduction respectively, record chromatogram, with isopulegol, benzoaric acid and interior target peak area ratio for vertical coordinate (Y), concentration (C) is abscissa (X), drawing standard curve, obtains regression equation and is respectively: Y(isopulegol respectively)=1.1148X-0.0016, R
2=0.9999, isopulegol concentration is at 0.146 ~ 2.555mgmL
-1in scope, linear relationship is good; Y(benzoaric acid)=1.1347X+0.0035, R
2=0.9998, benzoaric acid concentration is at 0.198 ~ 3.465mgmL
-1in scope, linear relationship is good.
3.6 precision test
Getting isopulegol concentration is 0.230mgmL
-1be 0.290mgmL with benzoaric acid concentration
-1reference substance solution, repeat sample introduction 6 times, record peak area, calculate 2 kinds of compositions and interior target peak area ratio (A/A is interior to be marked) respectively, the RSD of isopulegol, benzoaric acid be respectively 0.24% and 1.2%(n=6).
3.7 replica test
Get same batch sample, by the method replication under sample determination item 6 times, the RSD of result isopulegol, benzoaric acid be respectively 0.36%, 1.8%(n=6).
3.8 stability test
Get same batch sample solution, at room temperature place 0 respectively, 2,4,6,8, measure after 12h, result is respectively 0.38%, 1.7% by the RSD of isopulegol, benzoaric acid, and interpret sample solution measures in 12h, and result is stablized.
3.9 average recovery tests
Get the sample solution 9 parts of known content, and add suitable basic, normal, high reference substance solution, measure isopulegol, benzoaric acid content by sample determination method, calculate the response rate respectively, the results are shown in Table 3-1.
Table 3-1 determination of recovery rates result (n=9, %)
Result shows, the response rate of this method is better, the response rate of isopulegol is respectively 99.4% ~ 100.2%, the response rate of benzoaric acid is between 98.1% ~ 100.7%, relative standard deviation is respectively 0.28% and 0.86%, and this assay method can meet the assay of isopulegol and benzoaric acid in medicine of the present invention.
3.10 quantitative limit and detectability
Adopt " signal to noise ratio method " to determine quantitative limit and the detectability of this research, line taking standard solution is appropriate, employing add dehydrated alcohol progressively dilution method dilute, when sample introduction concentration is 6.27,9.90 μ gmL
-1time, get 1 μ L sample introduction, continuous sample introduction 3 times, obtain isopulegol, interior mark, benzoaric acid signal to noise ratio meansigma methods respectively close to 10.0, can with this concentration for quantitative limit; Continue dilution sample introduction, when sample introduction concentration is 1.044,1.65 μ gmL
-1, continuous sample introduction 3 times, obtains isopulegol, interior mark, benzoaric acid signal to noise ratio meansigma methods close to 3.0, can with this concentration for detectability.
3.11 serviceability test
Investigate and stability of solution investigation through different chromatographic column, and column temperature, injector temperature and detector temperature are investigated, and show this method good tolerance, are applicable to the assay of two components in medicine of the present invention.
3.11.1 the impact of chromatographic column
Select the chromatographic column of 3 different commercial specifications, measure the content of same batch sample, the RSD% calculating content value is respectively 1.3,1.7,1.6.Result shows, the different PEG chromatographic column of sample measures content, and isopulegol, benzoaric acid all can effectively be separated with interior mark, illustration method good tolerance.
3.11.2 the impact of column temperature
Column temperature is mainly on the impact be separated the appearance time affecting main peak, temperature is higher, main peak appearance time is shorter, when the first stage is 80 DEG C, isopulegol main peak isopulegol and impurity peak energy ensure baseline separation, during second stage 120 DEG C, benzoaric acid main peak and impurity peak energy ensure baseline separation, and the RSD of content is less than 2.0% at each temperature.
3.11.3 the impact of injector temperature
When injector temperature is higher than column temperature, isopulegol and impurity peaks can ensure baseline separation, and benzoaric acid and magazins' layout are good, and the RSD of content is less than 2.0% at each temperature.
3.11.4 the impact of detector temperature
When detector temperature is higher than injector temperature, isopulegol and impurity peaks can ensure baseline separation, and benzoaric acid and magazins' layout are good, and the RSD of content is less than 2.0% at each temperature.
3.12 sample size measurement result
Through Method validation, this content assaying method is easy and simple to handle, accuracy is high, favorable reproducibility, more effectively can control product quality.Therefore apply the method to 10 batch samples, adopt internal standard method to carry out assay according to preceding method, the results are shown in Table 3-2.
Table 3-2 sample size measurement result
4 discuss
4.1 system suitability test
Under this test gas chromatography system, each 1 μ L of pipette samples mensuration mixing reference substance solution, need testing solution and negative control solution respectively, record chromatogram.2 kinds of components all can be separated preferably with internal standard substance, negative noiseless.This system suitability the results are shown in Table 3-3.
Table 3-3 system suitability test
The selection of 4.2 internal standard substances
Once tried out Ketohexamethylene, naphthalene, biphenyl, methyl salicylate etc., because sample volatile ingredient is many, result with the retention time of Ketohexamethylene and separating effect most suitable.
The selection of 4.3 column temperatures
The boiling point difference of isopulegol, Ketohexamethylene and benzoaric acid is larger, when column temperature is low, the retention time of benzoaric acid is long, during column temperature height, isopulegol can not effectively be separated with impurity, analyzes while meeting two kinds of compositions through adopting two sections of temperature-programmed modes.
The content limit of 4.4 this product
By 10 batch products measurement results, the content limit of tentative this product is: the every 1g of this product must not be less than 0.200mg containing isopulegol, must not be less than 0.200mg containing benzoaric acid.
This method is carried out being separated to 2 kinds of compositions simultaneously and is detected, and method is quick, sensitive, and separating degree is good, specificity is good, effectively can control drug quality.
Detailed description of the invention:
Embodiment 1: medicine of the present invention
Prescription: Daphne giraldii Nitsche 1100g
Method for making: get Daphne giraldii Nitsche, decocts with water three times, 2 hours first times, for the second time, third time 1 hour, collecting decoction, filter, filtrate is concentrated into the clear paste that relative density is 1.22 1.26, adds ethanol and makes alcohol content reach 75%, leaves standstill and makes precipitation, get supernatant, reclaim ethanol and concentrate, adding calcium carbonate, starch, dextrin, mixing, makes granule, dry, be pressed into 1000, film coating or sugar-coat, to obtain final product.
Cure mainly: be used for the treatment of scapulohumeral periarthritis, epilepsy.
Usage and consumption: oral.One time 13,23 times on the one.
Detection method:
1, high-efficient liquid spectrometry is adopted to carry out assay to Daphne Giraldii Nitsche glycosides B:
(1) chromatographic condition: adopt HypersilDs chromatographic column; Mobile phase: ratio is the acetonitrile-water of 30:70; Determined wavelength: 200nm; Column temperature: 20 DEG C; Flow velocity: 1.0mLmin
-1; Sample size: 10 μ L;
(2) reference substance solution preparation: it is appropriate that precision takes 80 DEG C of Daphne Giraldii Nitsche glycosides B reference substances being dried to constant weight, adds dissolve with methanol and makes the reference substance solution of every 1mL containing 0.2mg;
(3) preparation of need testing solution: precision takes medicine 10g of the present invention, adds methanol 40mL, reflux 4h, extracting solution reflux solvent is also concentrated into dry, residue add water 10mL dissolve, extract 5 times with water saturated n-butyl alcohol jolting, each 20mL, merges n-butanol extracting liquid, washs 3 times with ammonia solution, each 15mL, n-butanol extracting liquid recycling design is to dry, and residue adds dissolve with methanol and is transferred in 10mL volumetric flask, add methanol to scale, shake up, filter, get filtrate, obtain need testing solution;
(4) measure: precision measures above-mentioned need testing solution, each 10 μ L of reference substance solution respectively, inject high performance liquid chromatograph, detect;
(5) measurement result: in every 1g this product containing Daphne Giraldii Nitsche glycosides B, must not 0.12mg be less than.
2, gas chromatography is adopted to carry out assay to isopulegol, benzoaric acid:
(1) chromatographic condition: chromatographic column: ZB-WAX fused-silica capillary column; Carrier gas: N
2, 1.0mLmL
-1; Hydrogen, 40mLmL
-1; Air, 400mLmin
-1; Split ratio: 10:1; Injector temperature: 250 DEG C, detector temperature 300 DEG C; Temperature programming: initial 80 DEG C, 5 DEG C per minute rise to 120 DEG C, and 10 DEG C per minute rise to 180 DEG C, keep 3.5min; Internal standard method;
(2) preparation of inner mark solution: get Ketohexamethylene appropriate, adds anhydrous alcohol solution and the solution of every 1mL containing 12.5mg is made in dilution, shakes up, as inner mark solution;
(3) preparation of need testing solution: precision measures this product 1.0g, puts in 10mL volumetric flask, add dehydrated alcohol and be diluted to scale, then precision measures 1.0mL, and put in 10mL volumetric flask, precision adds inner mark solution 1.0mL, adds dehydrated alcohol and is diluted to scale, shake up;
(4) preparation of reference substance solution: precision takes isopulegol reference substance, benzoaric acid reference substance is appropriate, adds anhydrous alcohol solution and dilution is made containing isopulegol 0.301mgmL
-1and benzoaric acid 0.901mgmL
-1reference substance stock solution, for subsequent use;
(5) measure: precision measures above-mentioned need testing solution, each 10 μ L of reference substance solution respectively, and inject gas chromatograph, detects;
(6) measurement result: the every 1g of this product must not be less than 0.200mg containing isopulegol, must not be less than 0.200mg containing benzoaric acid.
In addition, be to be understood that, although this description is described according to embodiment, but not each embodiment only comprises an independently technical scheme, this narrating mode of description is only for clarity sake, those skilled in the art should by description integrally, and the technical scheme in each embodiment also through appropriately combined, can form other embodiments that it will be appreciated by those skilled in the art that.
Claims (8)
1. a Giraldi daphne tablet medicine, is characterized in that, this medicine is made up of following raw material: Daphne giraldii Nitsche.
2. medicine as claimed in claim 1, is characterized in that, this medicine is adopted and prepared with the following method: get Daphne giraldii Nitsche, decoct with water three times, first time 2 hours, for the second time, third time 1 hour, collecting decoction, filter, filtrate is concentrated into the clear paste that relative density is 1.22 1.26, adds ethanol and makes alcohol content reach 75%, leaves standstill and makes precipitation, get supernatant, reclaim ethanol and concentrate, adding calcium carbonate, starch, dextrin, mixing, makes granule, dry, tabletted, film coating or sugar-coat, to obtain final product.
3. if the medicine in claim 1 ~ 2 as described in any one is for the preparation of the application in treatment AED or health product.
4. if the medicine in claim 1 ~ 2 as described in any one is for the preparation of the application in cure scapulohumeral periarthritis medicine or health product.
5. as the medicine in claim 1 ~ 2 as described in any one, it is characterized in that, adopt high performance liquid chromatography to carry out assay to Daphne Giraldii Nitsche glycosides B:
(1) chromatographic condition: adopt HypersilDs chromatographic column; Mobile phase: ratio is the acetonitrile-water of 20 ~ 40:60 ~ 80; Determined wavelength: 190 ~ 210nm; Column temperature: 15 ~ 25 DEG C; Flow velocity: 0.5 ~ 1.5mLmin
-1; Sample size: 5 ~ 20 μ L;
(2) reference substance solution preparation: it is appropriate that precision takes the Daphne Giraldii Nitsche glycosides B reference substance being dried to constant weight, adds dissolve with methanol and make reference substance solution;
(3) preparation of need testing solution: precision takes medicine of the present invention, adds methanol, reflux, extracting solution reflux solvent is also concentrated into dry, and residue is dissolved in water, and extracts with water saturated n-butyl alcohol jolting, merge n-butanol extracting liquid, with ammonia solution washing, n-butanol extracting liquid recycling design is to dry, and residue adds dissolve with methanol, shake up, filter, get filtrate, obtain need testing solution;
(4) measure: precision measures above-mentioned need testing solution, each 5 ~ 20 μ L of reference substance solution respectively, inject high performance liquid chromatograph, detect.
6. medicine as claimed in claim 5, is characterized in that, adopts high-efficient liquid spectrometry to carry out assay to Daphne Giraldii Nitsche glycosides B:
(1) chromatographic condition: adopt HypersilDs chromatographic column; Mobile phase: ratio is the acetonitrile-water of 30:70; Determined wavelength: 200nm; Column temperature: 20 DEG C; Flow velocity: 1.0mLmin
-1; Sample size: 10 μ L;
(2) reference substance solution preparation: it is appropriate that precision takes 80 DEG C of Daphne Giraldii Nitsche glycosides B reference substances being dried to constant weight, adds dissolve with methanol and makes the reference substance solution of every 1mL containing 0.2mg;
(3) preparation of need testing solution: precision takes medicine 10mL of the present invention, adds methanol 40mL, reflux 4h, extracting solution reflux solvent is also concentrated into dry, residue add water 10mL dissolve, extract 5 times with water saturated n-butyl alcohol jolting, each 20mL, merges n-butanol extracting liquid, washs 3 times with ammonia solution, each 15mL, n-butanol extracting liquid recycling design is to dry, and residue adds dissolve with methanol and is transferred in 10mL volumetric flask, add methanol to scale, shake up, filter, get filtrate, obtain need testing solution;
(4) measure: precision measures above-mentioned need testing solution, each 10 μ L of reference substance solution respectively, inject high performance liquid chromatograph, detect.
7. as the medicine in claim 1 ~ 2 as described in any one, it is characterized in that, adopt gas chromatography to carry out assay to isopulegol, benzoaric acid:
(1) chromatographic condition: chromatographic column: ZB-WAX fused-silica capillary column; Carrier gas: N
2, 0.5 ~ 1.5mLmL
-1; Hydrogen, 30 ~ 50mLmL
-1; Air, 300 ~ 500mLmin
-1; Split ratio: 5 ~ 15:1; Injector temperature: 240 ~ 260 DEG C, detector temperature: 290 ~ 310 DEG C; Temperature programming: initial 80 DEG C, 5 DEG C per minute rise to 120 DEG C, and 10 DEG C per minute rise to 180 DEG C, keep 3.5min; Internal standard method;
(2) preparation of inner mark solution: get Ketohexamethylene appropriate, adds anhydrous alcohol solution and solution is made in dilution, shakes up, as inner mark solution;
(3) preparation of need testing solution: precision measures this product, puts in volumetric flask, add dehydrated alcohol and be diluted to scale, then precision measures, and put in volumetric flask, precision adds inner mark solution, adds dehydrated alcohol and is diluted to scale, shake up;
(4) preparation of reference substance solution: precision takes isopulegol reference substance, benzoaric acid reference substance is appropriate, adds anhydrous alcohol solution and also dilutes the reference substance stock solution made containing isopulegol and benzoaric acid, for subsequent use;
(5) measure: precision measures above-mentioned need testing solution, each 5 ~ 20 μ L of reference substance solution respectively, and inject gas chromatograph, detects.
8. medicine as claimed in claim 7, is characterized in that, adopts gas chromatography to carry out assay to isopulegol, benzoaric acid:
(1) chromatographic condition: chromatographic column: ZB-WAX fused-silica capillary column; Carrier gas: N
2, 1.0mLmL
-1; Hydrogen, 40mLmL
-1; Air, 400mLmin
-1; Split ratio: 10:1; Injector temperature: 250 DEG C, detector temperature 300 DEG C; Temperature programming: initial 80 DEG C, 5 DEG C per minute rise to 120 DEG C, and 10 DEG C per minute rise to 180 DEG C, keep 3.5min; Internal standard method;
(2) preparation of inner mark solution: get Ketohexamethylene appropriate, adds anhydrous alcohol solution and the solution of every 1mL containing 12.5mg is made in dilution, shakes up, as inner mark solution;
(3) preparation of need testing solution: precision measures this product 1.0mL, puts in 10mL volumetric flask, add dehydrated alcohol and be diluted to scale, then precision measures 1.0mL, and put in 10mL volumetric flask, precision adds inner mark solution 1.0mL, adds dehydrated alcohol and is diluted to scale, shake up;
(4) preparation of reference substance solution: precision takes isopulegol reference substance, benzoaric acid reference substance is appropriate, adds anhydrous alcohol solution and dilution is made containing isopulegol 0.301mgmL
-1and benzoaric acid 0.901mgmL
-1reference substance stock solution, for subsequent use;
(5) measure: precision measures above-mentioned need testing solution, each 10 μ L of reference substance solution respectively, and inject gas chromatograph, detects.
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| CN201610083483.5A CN105535271A (en) | 2016-02-10 | 2016-02-10 | Girald daphne bark tablets for treating scapulohumeral periarthritis and nursing auxiliary medicine thereof for treating epilepsy |
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|---|---|---|---|
| CN201610083483.5A CN105535271A (en) | 2016-02-10 | 2016-02-10 | Girald daphne bark tablets for treating scapulohumeral periarthritis and nursing auxiliary medicine thereof for treating epilepsy |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105596559A (en) * | 2016-02-10 | 2016-05-25 | 陈武 | Girald daphne bark tablet for treating arthritis and nursing assistant medicine for metabolic syndrome |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1094627A (en) * | 1993-05-03 | 1994-11-09 | 周惠仁 | Giraldi daphne tablet and preparation method thereof |
| CN1362199A (en) * | 2001-01-02 | 2002-08-07 | 杨孟君 | Nano girald daphne medicine and its preparation |
| CN105596559A (en) * | 2016-02-10 | 2016-05-25 | 陈武 | Girald daphne bark tablet for treating arthritis and nursing assistant medicine for metabolic syndrome |
-
2016
- 2016-02-10 CN CN201610083483.5A patent/CN105535271A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1094627A (en) * | 1993-05-03 | 1994-11-09 | 周惠仁 | Giraldi daphne tablet and preparation method thereof |
| CN1362199A (en) * | 2001-01-02 | 2002-08-07 | 杨孟君 | Nano girald daphne medicine and its preparation |
| CN105596559A (en) * | 2016-02-10 | 2016-05-25 | 陈武 | Girald daphne bark tablet for treating arthritis and nursing assistant medicine for metabolic syndrome |
Non-Patent Citations (1)
| Title |
|---|
| 国家药典委员会编: "《中华人民共和国药典：2010年版.一部》", 31 January 2010, 中国医药科技出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105596559A (en) * | 2016-02-10 | 2016-05-25 | 陈武 | Girald daphne bark tablet for treating arthritis and nursing assistant medicine for metabolic syndrome |
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Effective date of registration: 20170913 Address after: 222023 No. 11 West Haining Road, Haizhou District, Jiangsu, Lianyungang Applicant after: Lianyungang Seamus Biological Technology Co. Ltd. Address before: 222004, room 3, unit 5, building 30, public security District, 101 Xin Kong South Road, trendy community, Haizhou District, Jiangsu, Lianyungang Applicant before: Chen Wu |
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Application publication date: 20160504 |