CN1876000A - 'Yan Lu Ru Kang' pharmaceutical preparation for treating mammary gland hyperplasia, its preparation process and quality control method - Google Patents
'Yan Lu Ru Kang' pharmaceutical preparation for treating mammary gland hyperplasia, its preparation process and quality control method Download PDFInfo
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Abstract
The invention relates to a pharmaceutical composition for treating lactiferous gland hyperplasia, the process for preparation and method for quality control, which mainly comprises rodgersflower rhizome 445g, pyrola 62.5g, deglued antler powder 7.5g or their extracts.
Description
Technical field: the present invention is a kind of YANLU RUKANG YAOWU ZHIJI and method for making and method of quality control for the treatment of cyclomastopathy, belongs to technical field of Chinese medicine.
Technical background: cyclomastopathy is that the women is common, one of frequently-occurring disease, is more common in 25～45 years old women, and it is the disorder of the mammary gland normal configuration that causes of a kind of physiology hypertrophy and subinvolution in essence.In China, capsule sexually revises rarely, how based on glandular hyperplasia, so claim " cyclomastopathy " more.The World Health Organization's general designation " optimum mammary dysplasia ".The normal women of the danger that primary disease cancerates increases 2-4 doubly, and clinical symptoms is mixed with breast carcinoma sometimes mutually with sign.Its main clinical characteristics is lump in breast and mastalgia, and general often increase the weight of in premenstrua alleviates after passing through.Because the seriously ill sub-fraction of cyclomastopathy has the probability that develops into breast carcinoma later on, so there is the people to think that cyclomastopathy is " precancerous lesion " of breast carcinoma.Cyclomastopathy belongs to the traditional Chinese medical science " nodules of the breast " category.The description of relevant primary disease sees " Huatuo's Zhongzang classic " the earliest, and later ancient Chinese medicine doctor has argumentation more, and its etiology and pathogenesis, clinical manifestation and treatment are all had detailed elaboration." nodules of the breast " is to describe functional activity of QI being not smooth distension pain to occur in breast portion, disease please the time time slack play, characteristics such as light Shi Chong during pain.Be to describe like this in " infections section heart moral collection ": " nodule in the breast is arranged, shape such as ball ovum, pain is not had a fever, and color of the leather is constant, and it examines the growth and decline with susceptible to anger, this nodules of the breast ...." this disease of Chinese medicine has one's own knack, wherein commercially available 'Yan Lu Ru Kang ' capsule is made of Rhizoma Rodgersiae, Cornu Cervi Degelatinatum, Herba Pyrolae, can hard masses softening and resolving, and the cyclomastopathy curative effect that is used for insufficiency of kidney-YANG, caused by energy stagnation and blood stasis is better.But Cornu Cervi Degelatinatum is a Cornu Cervi removes gelationus hornblock, and hygroscopicity is arranged, and that chews has a tooth gluing sense, causes the content of capsule easily to bond, and product stability is relatively poor, causes curative effect also to be affected; In view of such circumstances, in order to improve stability of drug, need a kind of therapeutic effect ideal of searching, reliable in quality, the reasonably effective medicine preparation of dosage form to enrich the dosage form kind, satisfy market demand; Not strict and standard is lower for the method for quality control of this quasi drugs in the prior art in addition, so often cause Producer that the quality of medicine is difficult to quantitative control, the patient also has no way of understanding the specific targets of medicine simultaneously.
Summary of the invention: the objective of the invention is to:, provide YANLU RUKANG YAOWU ZHIJI and the method for making and the method for quality control of treatment cyclomastopathy at prior art; This product has the effect of hard masses softening and resolving, and the cyclomastopathy, the curative effect that are used for the treatment of insufficiency of kidney-YANG, caused by energy stagnation and blood stasis are better.Product comprise have dosage accurately, steady quality, be convenient to transport storage, with low cost, can simplify production technology, reduce cost, carry the tablet of characteristics such as taking convenience; And have and be subjected to food to carry the influence of the rhythm and pace of moving things very little, drug absorption is even and regular, surface area increases can improve medicine and gastrointestinal contact area, make drug absorption complete, improve bioavailability, good looking appearance, good fluidity, release simultaneously stablized, local irritation is little, is difficult for the coated micropill preparation of characteristics such as moisture absorption, good mouthfeel; The present invention also provides the method for quality control to this medicine, can solve the existing in prior technology problem.
The present invention constitutes like this:
The YANLU RUKANG YAOWU ZHIJI of described treatment cyclomastopathy, main by Rhizoma Rodgersiae 445g, Herba Pyrolae 62.5g, Cornu Cervi Degelatinatum 7.5g or the effervescent tablet that is made with their extract of corresponding weight portion, injection, powder pin, freeze-dried powder, gel, dispersible tablet, capsule, soft capsule, microcapsule, granule, pill, micropill, powder, drop pill, slow releasing preparation, controlled release preparation, gel, oral liquid, soft extract, extractum or membrane.Be preferably tablet, granule or pellet.
The preparation method of the YANLU RUKANG YAOWU ZHIJI of described treatment cyclomastopathy is got Rhizoma Rodgersiae, adds 8 times of alcohol refluxs 3 times, 2 hours for the first time, second and third time each 1 hour, merge extractive liquid,, filter, filtrate recycling ethanol and when being concentrated into 50 ℃ relative density be 1.20 clear paste, standby; Other gets Herba Pyrolae, the Cornu Cervi Degelatinatum pulverize separately becomes fine powder, with above-mentioned Rhizoma Rodgersiae clear paste mixing, makes different preparations then respectively.
The 'Yan Lu Ru Kang ' tablet of described treatment cyclomastopathy is preparation like this: get Rhizoma Rodgersiae, add 8 times of alcohol refluxs 3 times, 2 hours for the first time, second and third time each 1 hour, merge extractive liquid, filters, filtrate recycling ethanol and when being concentrated into 50 ℃ relative density be 1.20 clear paste, standby; Other gets Herba Pyrolae, the Cornu Cervi Degelatinatum pulverize separately becomes fine powder, with above-mentioned Rhizoma Rodgersiae clear paste mixing, adds appropriate amount of starch, 4% Pulvis Talci and 5% microcrystalline Cellulose, and drying is pulverized, sieve, and tabletting, coating, coating material are Opadry 2, consumption is 6%, promptly.
The 'Yan Lu Ru Kang ' micropill of described treatment cyclomastopathy is preparation like this: get Rhizoma Rodgersiae, add 8 times of alcohol refluxs 3 times, 2 hours for the first time, second and third time each 1 hour, merge extractive liquid, filters, filtrate recycling ethanol and when being concentrated into 50 ℃ relative density be 1.20 clear paste, standby; Other gets Herba Pyrolae, the Cornu Cervi Degelatinatum pulverize separately becomes fine powder, with above-mentioned Rhizoma Rodgersiae clear paste mixing, add an amount of starch, with 70% ethanol and 1.2% soybean oil system soft material, the soft material that makes micropill mechanism ball, wet feed pushed the 0.8mm sieve aperture, the wet grain of strip cuts off round as a ball, 50～60 ℃ of drying and mouldings are crossed 16～20 mesh sieves and are selected ball or merge above-mentioned four kinds of clear paste, spray drying, wet-milling granulation molding, mould placed add the great achievement ball in the coating pan, medicated powder: water is 1: 1.5, and the coating pan rotating speed is 40r/min, capping, select ball, coating, 4%80W type Opadry is a coating material, the coating solution speed of spraying into is 150～180g/min, inlet temperature is for being controlled between 85～88 ℃, and pot body rotating speed is controlled at 4～6/min, promptly.
The method of quality control of the YANLU RUKANG YAOWU ZHIJI of described treatment cyclomastopathy comprises following all or part of content:
(1) all or part of differential test method in Rhizoma Rodgersiae, the Bergeninum;
(2) content test method of Bergeninum.
Wherein, discrimination method comprises one or both discriminating in Rhizoma Rodgersiae, the Bergeninum:
It is an amount of to get 'Yan Lu Ru Kang ' preparation content to be measured, adds methanol or ethanol extraction, filters, and filtrate is as need testing solution; Get the Rhizoma Rodgersiae control medicinal material, shine medical material solution in pairs with legal system; Get the Bergeninum reference substance, add methanol or dissolve with ethanol, make reference substance solution, draw need testing solution and reference substance solution 1～30 μ l, put in same silica gel G F respectively
25On lamellae or silica gel g thin-layer plate or the silica gel H lamellae, with chloroform or dichloromethane-ethyl acetate or Ethyl formate or butyl acetate-formic acid or acetic acid (1～5: 1～4: 0～2) be developing solvent, launch, take out, dry, put under the uviol lamp and inspect, in the test sample chromatograph, with control medicinal material or the corresponding position of reference substance chromatograph on, show the speckle of same color.
Specifically: the discrimination method of described preparation comprises one or both discriminating in Rhizoma Rodgersiae, the Bergeninum:
It is an amount of to get 'Yan Lu Ru Kang ' preparation content to be measured, therefrom takes by weighing 0.4g, adds methanol 3ml, and jolting 30 minutes filters, and filtrate is as need testing solution; The Rhizoma Rodgersiae medical material shines medical material solution in pairs with legal system; Other gets the Bergeninum reference substance, adds methanol and makes the solution that every 1ml contains 1mg, and product solution shines in contrast; Draw need testing solution 3 μ l, reference substance solution 10 μ l put in same silica gel G F respectively
254On the lamellae, be developing solvent, launch, take out, dry, put under the uviol lamp (254nm) and inspect with chloroform-ethyl acetate-formic acid (5: 4: 2), in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
The content assaying method of described preparation is the assay of Bergeninum:
It is an amount of to get 'Yan Lu Ru Kang ' preparation content to be measured, and mixing is therefrom got an amount of accurate the title and decided, and adds methanol or ethanol extraction, puts to room temperature, supplies the methanol or the ethanol of loss, shakes up, and filters, and gets subsequent filtrate, as need testing solution; It is an amount of that precision takes by weighing the Bergeninum reference substance, puts in the brown measuring bottle, adds methanol or ethanol is made reference substance solution; With octadecylsilane chemically bonded silica or eight alkyl silane bonded silica gels or dialkyl silane bonded silica gel is filler, methanol or acetonitrile-water (5～30: 60～95) be mobile phase, detect wavelength and be among 190～410nm one or several; Calculate with standard curve method or one point external standard method, 'Yan Lu Ru Kang ' formulation content limit to be measured should be: one with containing Rhizoma Rodgersiae in the 'Yan Lu Ru Kang ' preparation with Bergeninum (C
14H
16O
9) meter, must not be less than 27mg.
Preferred content assaying method is:
It is an amount of to get 'Yan Lu Ru Kang ' preparation content to be measured, and mixing is therefrom got about 0.4g, the accurate title, decide, and puts in the brown measuring bottle of 50ml, and it is an amount of to add methanol, supersound process (power 250W, frequency 33KHz) 40 minutes is taken out, put to room temperature, add methanol and be diluted to scale, shake up, filter with microporous filter membrane (0.45 μ m), get subsequent filtrate, as need testing solution; It is an amount of that precision takes by weighing the Bergeninum reference substance, puts in the brown measuring bottle, adds methanol and make the solution that every 1ml contains 0.15mg, in contrast product solution; With octadecylsilane chemically bonded silica is filler, and methanol-water (18: 82) is a mobile phase, and the detection wavelength is 275nm; Calculate with one point external standard method, 'Yan Lu Ru Kang ' formulation content limit to be measured should be: one with containing Rhizoma Rodgersiae in the 'Yan Lu Ru Kang ' preparation with Bergeninum (C
14H
16O
9) meter, must not be less than 54mg.
Compared with prior art, the present invention is directed to prior art, the 'Yan Lu Ru Kang ' novel formulation is provided, product has the effect of hard masses softening and resolving, is used for the treatment of the cyclomastopathy, evident in efficacy of insufficiency of kidney-YANG, caused by energy stagnation and blood stasis; Comprise Film coated tablets and granule in the product with characteristics such as easy to carry, good mouthfeels, and have and be subjected to food to carry the influence of the rhythm and pace of moving things very little, drug absorption is even and regular, surface area increases can improve medicine and gastrointestinal contact area, make drug absorption complete, improve bioavailability, good looking appearance, good fluidity, release simultaneously stablized, local irritation is little, is difficult for the coated micropill preparation of characteristics such as moisture absorption, good mouthfeel; Preparation method that provides and method of quality control can reasonablely instruct enterprise's suitability for industrialized production; Can guarantee product quality; Overcome the problem that prior art, product exist; Reached the purpose of invention.
The applicant finds that under study for action because the Cornu Cervi Degelatinatum hygroscopicity that we use is very strong, conventional method is made tablet, micropill moisture absorption phenomenon can occur in put procedure, influenced the stability and the quality of product.So product has been carried out art for coating research, has played and improved mouthfeel and moisture-resistant purpose.In research process, find, coating material, the improper meeting of process choice delay the disintegrate and molten the loosing of product of the present invention, so the applicant has carried out a series of experiments, select the supplementary product kind of preparation technology, use of the most suitable pharmaceutical preparation of the present invention and consumption, ratio etc.; Guarantee its science, reasonable, feasible; The preparation that obtains has good disintegrating property and therapeutic effect.And the method for quality control of existing 'Yan Lu Ru Kang ' preparation is comparatively rough, is difficult to reach modern medicines requirement stable and controllable for quality.Therefore, the new method that needs the control of the research 'Yan Lu Ru Kang ' quality of the pharmaceutical preparations.
Experimental example 1: medical material pre-treatment
Herba Pyrolae, the research of Cornu Cervi Degelatinatum disintegrating process: Herba Pyrolae becomes fine powder with the Cornu Cervi Degelatinatum pulverize separately, crosses 80 orders, and is standby.Disintegrating process sees the following form.
The Herba Pyrolae disintegrating process is investigated the result
| Medical material | Inventory (kg) | Quantities received (kg) | Flour extraction (%) |
| 2 | 1.81 | 90.5 | |
| Herba Pyrolae | 2 | 1.80 | 90.0 |
| 2 | 1.78 | 89.0 |
From top data as can be seen, the flour extraction of three pulverizing is more approaching, illustrates that this condition is stable, must not be lower than 89.0% so Herba Pyrolae is pulverized recovery rate.
The Cornu Cervi Degelatinatum disintegrating process is investigated the result
| Medical material | Inventory (g) | Quantities received (g) | Flour extraction (%) |
| 100 | 92.4 | 92.4 | |
| Cornu Cervi Degelatinatum | 100 | 91.0 | 91.0 |
| 100 | 92.2 | 92.2 |
Through the research of above-mentioned test as can be seen, Cornu Cervi Degelatinatum pulverize cross 80 mesh sieves in the back flour extraction on average 91.8%, determine that therefore the Cornu Cervi Degelatinatum flour extraction is not less than 91%.
Experimental example 2: Study on extraction
(1) factor is selected: the Chinese medicine extraction effect is subjected to the influence of factors such as solvent species, solvent load, extraction time, extraction time.Though prior art is investigated extraction time, extraction time, but when the Rhizoma Rodgersiae medicinal material extract is investigated, choose extraction solvent species and solvent load and do not make a search.Take all factors into consideration the selection factor level in conjunction with aspects such as production cost, the energy.
(2) index is determined: select extractum recovery rate and Bergeninum content as evaluation index, its reason and assay method are as follows:
1. extractum recovery rate: extractum is the material base of solid preparation performance curative effect, and its yield height directly influence preparation process, is reasonable, effective control device so be chosen as the extraction index.
2. assay: extractum recovery rate height can not reflect fully that active ingredient extracts situation, extracts screening index so measure the contained Bergeninum content of extractum simultaneously as Rhizoma Rodgersiae.
(3) test:
1. the ethanol consumption is investigated: take by weighing Rhizoma Rodgersiae 500g, totally 3 parts, add not commensurability ethanol respectively, reflux, extract, 3 times, 2 hours for the first time, second and third time each 1 hour, merge extractive liquid,, filter, filtrate recycling ethanol concentrates, drying under reduced pressure, claim fixed dried cream weight, measure Bergeninum content in the dried cream simultaneously, result of the test sees the following form.
Solvent load is investigated table as a result
| Tested number | Solvent load (doubly) | Extractum recovery rate (%) | Bergeninum content (%) |
| 1 | 6 | 31.68 | 4.70 |
| 2 | 8 | 34.17 | 4.66 |
| 3 | 10 | 34.65 | 4.54 |
As seen from the above table, adopt 8 times of amounts and adopt 10 times of amount gained extractum amounts and content difference little, illustrate that therefore adding 8 times of amount ethanol can fully extract medical material, determine that the optimised process of amount of water is 8 times of amounts.
(4) demonstration test: by the front series of selection, optimize the process conditions that Rhizoma Rodgersiae is extracted, we carry out demonstration test, result such as following table after the condition after preferred is made up.
Rhizoma Rodgersiae extraction conditions demonstration test
| Medical material amount (g) | Cream heavy (g) | Extractum recovery rate (%) | Bergeninum content (%) |
| 500.01 | 178.64 | 35.73 | 4.61 |
| 500.04 | 180.02 | 36.00 | 4.58 |
| 500.03 | 178.55 | 35.71 | 4.63 |
From last table as seen, Rhizoma Rodgersiae extraction conditions more stable (average paste-forming rate is 35.81%), the content of gained sample is also more stable, illustrates that the experimental condition through screening is feasible.
Experimental example 3: Study on Forming
3.1 tablet
(1) hygroscopicity is investigated
Cortex Phellodendri powder is broken into fine powder in the former technology, and we carry out hygroscopicity investigation test to the mixed material that extraction ointment, ointment add behind Herba Pyrolae and the Cornu Cervi Degelatinatum medicated powder, the results are shown in following table.
The wettability test result
| Sample | Extract powder+crude drug powder | Extract powder+crude drug powder | |
| The weighing bottle numbering | 1 | 2 | |
| Weight of material (g) | 4.99 | 5.02 | |
| Moisture absorption blanking time percentage (%) | 1h | 2.56 | 2.78 |
| 2h | 5.17 | 5.73 | |
| 3h | 6.84 | 6.51 | |
| 4h | 9.17 | 9.00 | |
| 6h | 10.77 | 10.81 | |
| 8h | 12.64 | 12.10 | |
| 10h | 14.11 | 13.92 | |
| 12h | 17.27 | 17.68 | |
| 24h | 19.51 | 20.05 | |
| 36h | 23.02 | 23.16 | |
| 48h | 27.24 | 27.96 | |
| 72h | 30.50 | 30.63 | |
| 84h | 32.66 | 32.42 | |
Investigate by wettability test, think that mixing ointment has certain moisture.
(2) the mobile investigation: for guaranteeing that divided dose is accurate, require the good flowability of fill material tool, so to measure the flowability of method examination angle of repose mixed material.
Fixed funnel method: get 3 funnel series connection, lowermost end is apart from horizontal positioned graph paper 1.5cm place, carefully fill material is poured into along hopper walls in the funnel of going up most till the granule cone tip that bottom funnel forms touches the funnel end opening, measure the diameter of conical base by graph paper, (tg α=H/R/2), result of calculation sees the following form to calculate angle of repose.
α angle of repose of fill material
| Working sample | Angle of repose |
| 1 | 55.3° |
| 2 | 54.4° |
| 3 | 55.8° |
As seen from the above table, mixed material angle of repose＞40 ° show that promptly the mixed material property that flows is bad, can not satisfy the branch reload request.
(3) diluent is selected: select for use starch as diluent in the former dosage form, consider that the material properties of extraction is basic identical, so we also select for use starch as diluent, starch has suction and non-deliquescent character can prevent the material moisture absorption simultaneously.
(4) fluidizer is investigated: from top angle of repose measurement result as can be seen, mixed material mobile relatively poor, divided dose is accurate when guaranteeing that capsule is loaded, and needs the flowability of increase fill material, we screen fluidizer for this reason.Fluidizer at present commonly used has starch, Pulvis Talci and micropowder silica gel etc. owing to used starch as diluent in the mixed material, still no longer consider to add again its consumption; Pulvis Talci can increase lubricity and flowability, and possess hydrophilic property, can not influence the disintegrate of tablet, thus we to adopt Pulvis Talci be fluidizer, and its consumption is investigated, result of the test sees the following form.
The amount of talc investigation table
| Sequence number | Amount of talc (%) | Angle of repose (°) |
| 1 | 1 | 46.5 |
| 2 | 4 | 33.1 |
| 3 | 7 | 32.3 |
From top result as can be seen, consumption was at 1% o'clock, improve to some extent the angle of repose to mixed material, but can't meet the demands, consumption is 4% and can reaches requirement at 7% o'clock, but amount of talc is 7% o'clock, and angle of repose, decline scope was not clearly, so we determine that amount of talc is 4%.
(5) disintegrating agent is selected: through the screening of above-mentioned test, adopt starch and Pulvis Talci to solve the problem of the material moisture absorption and mobile difference, make material can have certain moisture resistance and good flowability, but we find through trial test, the disintegration time of tablet is long behind the tabletting, therefore we investigate disintegrating agent, disintegrating agent commonly used at present has starch, microcrystalline Cellulose etc., because this preparation has adopted starch as diluent, microcrystalline Cellulose and starch mixing is simultaneously used and can be accelerated disintegrate, therefore determine the disintegrating agent microcrystalline Cellulose, and its consumption investigated that result of the test sees the following form.
The disintegrating agent investigation table
| Batch | Total weight of material (g) | Disintegrating agent consumption (g) | Disintegration time (branch) |
| 1 | 100 | 2 | 48 |
| 2 | 100 | 5 | 32 |
| 3 | 100 | 8 | 31 |
From above-mentioned test as can be seen, the disintegrating agent of adding 5% or 8% can effectively improve the disintegration time of tablet, but the disintegrating agent of 8% disintegrating agent relative 5%, and the disintegration time fall is not obvious, for the least possible adjuvant of taking, we select 5% disintegrating agent for use.
(6) coating conditions is investigated: because Chinese medicine extract has certain bad smell, in order to cover bad abnormal smells from the patient, make the patient be easy to swallow, the outward appearance of sample is improved, we wrap film-coat to plain sheet at decision, and through investigation, we select for use Opadry 2 to carry out coating.
1. coating solution is selected: in order to guarantee the quality behind the tablet coating, special coating is investigated with the consumption of adjuvant Opadry 2.The compound method of the Opadry 2 that provides according to Shanghai Colorcon Coating Technology Co., Ltd takes by weighing Opadry 2 pressed powders of requirement, adds the water of aequum in the preparation container, and stirring arm is placed on the central authorities of container, and as far as possible near the bottom of container.Agitating solution makes it form a whirlpool, avoids being involved in too much air simultaneously.The Opadry powder is added equably, avoid powder to swim in liquid surface simultaneously as far as possible.In case of necessity, can improve rotating speed to keep suitable whirlpool, treat that all Opadries all add after, reduce mixing speed, whirlpool is disappeared, continue to stir and got final product in 45 minutes.
2. wrap film-coat: plain sheet requires label smooth, no crimping, no fine powder, no fragment, hardness is positioned over satisfactory plain sheet in the coating pan at 3.5kg～4.5kg, opens coating pan, the crawl preheating, selecting inlet temperature is about 60 ℃, makes about label preheating temperature to 45 ℃.Open coating pan, rotate, start air compressor, spray coating solution, after 1 hour, improve rotating speed to 8～10 rev/min, sprayed fully, reduce rotating speed up to coating solution with spray gun with 3 rev/mins speed, drying, cooling gets final product.
The coating material consumption is investigated
| Tested number | Opadry 2 consumptions (%) | Tablet film-coat character |
| 1 | 3 | Film-coat is too thin, and pit is arranged |
| 2 | 6 | Film-coat is even |
| 3 | 9 | The film-coat local shedding, air spots is sliding |
As seen from the above table: the coating material consumption is 6% o'clock, and the gained film-coat is even, smooth.Therefore film-coat packaging material consumption is defined as 6%.
3.2 pellet
(1) consumption of coating material
Tested number coating powder consumption coated tablet outward appearance
The clothing layer of 1 3% coated tablet owes even
The clothing layer color even of 2 4% coated tablet is complete
The clothing layer of 3 5% coated tablet all owes even
(2) screening of art for coating
Parameter process I technology II technology III technology IV
Flow velocity (g/min) 110-140 150-180 230-250 270-300
Inlet temperature (℃) 95-98 85-88 88-85 85-80
Pot body rotating speed (r/min) 2-4 4-6 7-9 10-12
Different process micropill mass change
The average dissolution of technology (%) average moisture gross weight (kg) packaging material utilization rate (%)
Technology I coating preceding 95.7 3.40 100
Behind the coating 81.4 2.76 102.4 55.80
Technology II coating preceding 94.3 3.33 100
Behind the coating 90.8 2.26 103.2 59.56
Technology III coating preceding 94.0 3.15 100
Behind the coating 82.6 2.48 102.3 70.11
Technology IV coating preceding 93.9 3.03 100
Behind the coating 67.3 2.79 105.7 75.15
Experimental result as can be known, best art for coating: 4%80W type Opadry is a coating material, the coating solution speed of spraying into is 150～180g/min, inlet temperature is for being controlled between 85～88 ℃, a pot body rotating speed is controlled at 4～6/min, to the minimum that influences of medicine stripping.
(3) accelerated test and the room temperature assay that keeps sample
The little agent capsules agent of the present invention
Disintegration, (min) outward appearance differentiated that disintegration, (min) outward appearance was differentiated
Accelerated test 1 month 26 good 24 is good
Accelerated test 2 months 29 good 25 is good
3 months 30 a small amount of moisture absorptions of good 29 contents of accelerated test, bonding
2 years 30 good 28 moisture absorptions of storage at normal temperature, bonding
Experimental example 4: pharmacodynamic experiment
Get the female not pregnant rat of growing up, body weight 250 ± 20g through vaginal exfoliated cell smear 3 cyclic checks continuously, selects oestrous cycle rule person to experimentize.
Treating excess syndrome is tested the outside intramuscular injection of animal diethylstilbestrol injection hind leg, each 0.2mg, and every day 1 time, totally 30 days, accumulated dose was every 6mg.Check breast outward appearance and mammary gland pathological change.See that modeling rat papilla diameter, length significantly increase.Get 3 pairs of mammary gland of abdominal part caudal part and carry out check pathological section, see that the breast duct chamber enlarges, and is full of secretions in the tube chamber.Mammary gland acinus number showed increased.Epithelial hyperplasia is multiple layer or false multiple layered arrangement.Proof modeling success.
Get 70 of rats, be divided into 7 groups at random, 10 every group, handle as follows: normal group, distilled water is irritated stomach, every 2ml/d; Every day, distilled water was irritated stomach 1 time simultaneously for model group, modeling, each 2ml; 'Yan Lu Ru Kang ' Capsules group, group of products of the present invention, cyclomastopathy modeling add with related drugs respectively simultaneously irritates stomach, and dosage is 10 times of adult's routine dose, every day 1 time, each 2ml.Each organized the rat continuous medicine-filling 30 days, after 1 week of drug withdrawal, randomly drawed 7 rat mammary glands for every group between rutting period ,-70 ℃ of liquid nitrogen cryopreservations, estradiol receptor to be measured (ER), progesterone receptor (PR); 3 mammary gland specimen of every group of residue, 10% neutral formalin is fixed, routine paraffin wax section, HE dyeing, row pathologic finding (employing optical microscope).Adopt radiative aglycone combination assay Expression of Estrogen and Progesterone Receptors, measure the sample protein concentration with the Lowry method, content receptor is represented with fmol/mg.
(1) to the influence of hyperplasia of mammary gland model rat mammary gland ponderal index
Cause the model of rat mammary gland hamartoplasia for the heavy dose of intramuscular injection diethylstilbestrol of adult rat longer-term, every group of 7 pairs of mammary gland randomly drawing are carried out ponderal index (mg/100g body weight) relatively, the results are shown in following table.
Influence to the rat mammary gland ponderal index
| Group | The animal number of elements | Mammary gland ponderal index (mg/100g body weight) |
| Normal group model group 'Yan Lu Ru Kang ' Capsules group micropill group of the present invention sheet group of the present invention granule group of the present invention dispersing tablet group of the present invention | 7 7 7 7 7 7 7 | 18.51±2.06 23.84±3.42 18.83±1.81 18.56±4.84 18.71±2.53 18.79±5.13 18.50±5.17 |
(2) to the influence of hyperplasia of mammary gland model rat mammary gland organizational structure
Compare with the normal rat mammary gland tissue, whole 3 the rat mammary gland specimen of model group all have acinus quantity obviously to increase, and epithelial proliferation is false multiple layer phenomenon, severe patient even obstruction conduit; Ductal ectasia includes a large amount of secretions; Matter obviously reduces between reactivity on every side, and dyeing deepens, and the collagen hypertrophy loses rarefaction.And dosing respectively organizes acinus hypertrophy arranged, but degree obviously is lighter than model group, does not have significant difference between each dosing group.
(3) influence of, progesterone receptor female to the hyperplasia of mammary gland model rat mammary gland
Concrete outcome sees the following form.EcR Bmax represents rat mammary gland cytoplasmic estradiol receptor quantity in the table, and EnR Bmax represents nuclear estradiol receptor quantity, and EnR/EcR represents karyon/cytoplasmic estradiol receptor ratio; PcR Bmax represents rat mammary gland endochylema pregnanediol acceptor quantity, and PnR Bmax represents karyon pregnanediol acceptor quantity, and PnR/PcR represents karyon/endochylema pregnanediol receptor ratio; Kd represents receptor affinity, and the Kd value is more little, and affinity is high more.
Influence to hyperplasia of mammary gland model rat mammary gland estrogen receptor
| Group | Bmax(fmol/mg) | EnR/EcR | Kd(nmol/L) | ||
| EcR | EnR | EcR | EnR | ||
| Normal group model group 'Yan Lu Ru Kang ' Capsules group micropill group of the present invention sheet group of the present invention granule group of the present invention | 26.34±3.51 35.76±1.67 37.08±2.81 37.26±1.82 36.58±2.07 33.26±2.47 | 52.76±3.35 57.12±5.48 67.28±4.73 69.47±2.61 66.25±3.80 62.54±5.71 | 2.01±0.10 1.60±0.33 1.81±0.16 1.86±0.14 1.81±0.18 1.84±0.32 | 0.56±0.12 0.63±0.05 0.49±0.08 0.45±0.15 0.46±0.04 0.48±0.19 | 2.09±0.32 1.89±0.25 1.24±0.38 1.15±0.16 1.36±0.24 1.53±0.46 |
Influence to hyperplasia of mammary gland model rat mammary gland progesterone receptor
| Group | Bmax(fmol/mg) | PnR/PcR | Kd(nmol/L) | ||
| PcR | PnR | PcR | PnR | ||
| Normal group model group 'Yan Lu Ru Kang ' Capsules group micropill group of the present invention sheet group of the present invention granule group of the present invention | 14.98±1.37 12.62±2.18 15.64±1.35 17.88±5.18 15.97±2.32 16.52±5.51 | 34.28±8.94 33.76±4.85 36.22±3.74 37.48±7.43 37.32±5.71 37.05±6.54 | 2.29±0.62 2.68±0.45 2.32±0.19 2.10±0.14 2.34±0.21 2.24±0.34 | 0.78±0.21 1.21±0.15 0.82±0.24 0.72±0.05 0.80±0.22 0.77±0.27 | 1.69±0.23 2.09±0.12 1.78±0.18 1.81±0.11 1.69±0.35 1.75±0.15 |
Above experimental result shows that modeling animal mammary gland ponderal index after using 'Yan Lu Ru Kang ' capsule, product of the present invention obviously descends, and mammary structure is obviously improved; Simultaneously, can make female, progestogen nuclear/slurry receptor ratio all near normal, thereby the enhancing body balance has weakened the pessimal stimulation that a large amount of estrogen cause from steady regulating system function, has safeguarded the balance and stability of body; And the effect of product of the present invention is better than the 'Yan Lu Ru Kang ' capsule.
The thin layer of Bergeninum is differentiated in experimental example 5 tablets
The purpose of this experiment is the feature for outstanding Rhizoma Rodgersiae, and for getting rid of in the preparation and the similarly interference of other composition of Rhizoma Rodgersiae ingredient, the experimenter compares test respectively to sample extraction, development system, coloration method etc.Through screening, the best approach and condition have been determined: be the sample extraction solvent with methanol; With silica gel G F
254Lamellae is an immobile phase, and chloroform-ethyl acetate-formic acid (5: 4: 2) is developing solvent; Put under the uviol lamp (254nm) and inspect; With this understanding, it is clear that sample and reference substance all separate, negative noiseless.The expansion effect of several development systems relatively sees the following form in the experiment:
The thin layer of Rhizoma Rodgersiae, Bergeninum is differentiated in the tablet
| Developing solvent | Lamellae | Effect |
| Cyclohexane extraction-ethanol-formic acid (7: 5: 1) | Silica gel G | Difference: sample separation is unintelligible, and feminine gender has interference |
| Chloroform-ethyl acetate-methanol (7: 4: 2) | Silica gel G F 254 | Difference: feminine gender has interference |
| Chloroform-butyl acetate-acetic acid (10: 7: 4) | Silica gel H | Generally: it is clear that sample and reference substance all separate, and speckle is rounding not, negative noiseless |
| Chloroform-ethyl acetate-formic acid (5: 4: 2) | Silica gel G F 254 | Best: it is clear, negative noiseless that sample and reference substance all separate |
The assay of Bergeninum in experimental example 6 tablets
Test is reference substance with the Bergeninum, with Alltech P426 high performance liquid chromatograph, has established the best approach of the assay of Bergeninum in the featherleaf rodgersflower and pyrola herb contained tablet for treating mammary disease:
The chromatographic condition octadecylsilane chemically bonded silica is a filler; Methanol-water (18: 82) is a mobile phase; The detection wavelength is 275nm.Number of theoretical plate calculates by the Bergeninum peak should be not less than 2000.
It is an amount of that the preparation precision of reference substance solution takes by weighing the Bergeninum reference substance, puts in the brown measuring bottle, adds methanol and make the solution that every 1ml contains 0.15mg, promptly.
10 of this product are got in the preparation of need testing solution, remove coating, the porphyrize mixing, therefrom get about 0.4g, the accurate title, decide, and puts in the brown measuring bottle of 50ml, it is an amount of to add methanol, supersound process (power 250W, frequency 33KHz) 40 minutes, take out, put, add methanol and be diluted to scale to room temperature, shake up, filter with microporous filter membrane (0.45 μ m), get subsequent filtrate, promptly.
Accurate respectively reference substance solution and each the 5 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
Every of this product contains Rhizoma Rodgersiae with Bergeninum (C
14H
16O
9) meter, must not be less than 6.0mg.
This method has been passed through following 1～10 methodological study test respectively:
1 detects the selection Bergeninum reference substance solution of wavelength, in the interscan of 200～400nm wave-length coverage.The result shows that Bergeninum has bigger absorption at the 275nm place, therefore selects 275nm as the detection wavelength of measuring Bergeninum content in the 'Yan Lu Ru Kang ' tablet.
2 system suitability test obtain Bergeninum reference substance, sample chromatogram figure according to above instrument condition, and its theoretical cam curve is not less than 2000 in Bergeninum.
The test of 3 negative ELIMINATION OF ITS INTERFERENCE is for investigating the mensuration whether other medical material and adjuvant disturb Bergeninum, except that Bergeninum, takes by weighing other medical material and adjuvant is made negative control product solution and mensuration with method in the prescription ratio.The result shows that negative sample is noiseless to the assay of Bergeninum.
The investigation precision of 4 linear relationships is measured the solution of Bergeninum reference substance variable concentrations, injects chromatograph of liquid, and extracting solution is according to the disclosed high effective liquid chromatography for measuring of Chinese Pharmacopoeia.Sample size (μ g) with Bergeninum is an abscissa, and peak area is that vertical coordinate is figure, the drawing standard curve.See the following form.
The Bergeninum linear relationship
| Numbering | Bergeninum amount (μ g) | Peak area |
| 1 | 0.3074 | 281432 |
| 2 | 0.6148 | 550427 |
| 3 | 0.9222 | 828135 |
| 4 | 1.2296 | 1108174 |
| 5 | 1.5370 | 1390266 |
Regression equation: Y=902868X-937.7
Correlation coefficient: γ=0.9999
The result shows that Bergeninum linear relationship within 0.3074 μ g～1.5370 μ g scopes is good.
The selection of 5 sample extraction times
Get 10 of this product, remove coating, the porphyrize mixing, therefrom get about 0.4g (totally 4 parts), the accurate title, decide, and splits in the brown measuring bottle of 50ml, it is an amount of to add methanol, and supersound process (power 250W, frequency 33KHz) is 20,30,40,50 minutes respectively, take out, put, add methanol and be diluted to scale to room temperature, shake up, filter with microporous filter membrane (0.45 μ m), get subsequent filtrate, promptly.See the following form.
The selection of sample extraction time
| Extraction time (min) | Bergeninum (mg/ sheet) |
| 20 | 7.64 |
| 30 | 7.82 |
| 40 | 7.94 |
| 50 | 7.96 |
The result shows that supersound process 40min can extract fully, so extraction time is decided to be 40 minutes.
The accurate Bergeninum reference substance solution 5 μ l that draw of 6 precision test inject chromatograph of liquid, and replication 5 times is investigated reference substance solution precision, and measurement result sees the following form.
The precision test
| Test number (TN) | 1 | 2 | 3 | 4 | 5 | Meansigma methods | RSD(％) |
| Peak area | 682554 | 689713 | 687258 | 688315 | 692354 | 688039 | 0.53 |
The result shows that reference substance solution precision is good.
7 stability tests
7.1 the reference substance stability test is accurate the absorption with a Bergeninum reference substance solution 5 μ l at 0,2,6,10,24 hour respectively, injects chromatograph of liquid, measurement result sees the following form.
Reference substance solution stability test result
| Time (h) | 0 | 2 | 6 | 10 | 24 | Meansigma methods | RSD(％) |
| Peak area | 201307 | 203271 | 203941 | 200859 | 204306 | 202737 | 0.77 |
The result shows that reference substance solution is good at 24 hours internal stabilities.
7.2 the need testing solution stability test is accurate the absorption with a need testing solution 5 μ l at 0,2,6,10,24 hour respectively, injects chromatograph of liquid, measurement result sees the following form.
Need testing solution stability test result
| Time (h) | 0 | 2 | 6 | 10 | 24 | Meansigma methods | RSD(％) |
| Content (mg/ sheet) | 7.84 | 7.73 | 8.02 | 7.89 | 7.92 | 7.88 | 1.35 |
The result shows that need testing solution is good at 24 hours internal stabilities.
8 replica tests are got 10 of this product, remove coating, and the porphyrize mixing is therefrom got about 0.4g (totally 5 parts), and precision claims fixed, by operating under preparation of text need testing solution and the mensuration item.The results are shown in following table.
Replica test
| Time (h) | 0 | 2 | 6 | 10 | 24 | Meansigma methods | RSD(％) |
| Content (mg/ sheet) | 7.87 | 8.12 | 7.85 | 8.06 | 7.91 | 7.96 | 1.52 |
The result shows that repeatability is good.
The test of 9 average recoveries
Get this product under the weight differential item, porphyrize is therefrom got about 0.2g (totally 6 parts), and accurate the title decides, and splits in the brown measuring bottle of 50ml; Get the about 3.2mg of Bergeninum reference substance, 4.0mg, 4.8mg (each 2 parts), the accurate title, decide, and splits in the brown measuring bottle of above-mentioned 50ml, it is an amount of to add methanol, supersound process (power 250W, frequency 33KHz) 40 minutes, take out, put, add methanol and be diluted to scale to room temperature, shake up, filter with microporous filter membrane (0.45 μ m), the accurate subsequent filtrate 5 μ l that draw inject chromatograph of liquid, measure, promptly.Measurement result sees the following form.Bergeninum amount: 19.762mg/g in the featherleaf rodgersflower and pyrola herb contained tablet for treating mammary disease
The test of Bergeninum average recovery
| Numbering | Test sample weighing (g) | Pure product amount (mg) in the test sample | Bergeninum addition (mg) | The amount of recording (mg) | The response rate (%) |
| 1 | 0.20213 | 3.995 | 3.38 | 7.288 | 97.43 |
| 2 | 0.20175 | 3.987 | 3.26 | 7.134 | 96.53 |
| 3 | 0.20094 | 3.971 | 3.94 | 7.853 | 98.53 |
| 4 | 0.20468 | 4.045 | 4.17 | 8.126 | 97.87 |
| 5 | 0.20365 | 4.025 | 4.92 | 8.857 | 98.21 |
| 6 | 0.20093 | 3.971 | 5.03 | 8.963 | 99.24 |
Bergeninum average recovery rate=97.97%, RSD=0.95%;
10 sample sizes are measured the preparation and the operation down of algoscopy item of pressing the text need testing solution, measure ten batch samples, the results are shown in following table.
Ten batch sample assay results
| Lot number | Bergeninum (mg/ sheet) |
| 031101 | 7.57 |
| 031102 | 12.42 |
| 031103 | 8.26 |
| 031104 | 10.13 |
| 031201 | 6.24 |
| 031202 | 9.05 |
| 031203 | 7.81 |
| 040301 | 7.54 |
| 040302 | 7.32 |
| 040303 | 7.68 |
Conclusion: tentative according to 10 batch sample assay results, every of this product contains Rhizoma Rodgersiae with Bergeninum (C
14H
16O
9) meter, must not be less than 6.0mg.This product one day is with containing Rhizoma Rodgersiae in the dosage tablet with Bergeninum (C
14H
16O
9) meter, must not be less than 54mg.
Concrete embodiment:
Embodiments of the invention 1: Rhizoma Rodgersiae 445g, Herba Pyrolae 62.5g, Cornu Cervi Degelatinatum 7.5g
Get Rhizoma Rodgersiae, add 8 times of 80% alcohol reflux 3 times, 2 hours for the first time, second and third time each 1 hour, merge extractive liquid, filters, filtrate recycling ethanol and when being concentrated into 50 ℃ relative density be 1.20 clear paste, standby; Other gets Herba Pyrolae, the Cornu Cervi Degelatinatum pulverize separately becomes fine powder, with above-mentioned Rhizoma Rodgersiae clear paste mixing, adds appropriate amount of starch, 4% Pulvis Talci and 5% microcrystalline Cellulose, drying is pulverized, and sieves, tabletting, coating, coating material are Opadry 2, and consumption is 6%, promptly get tablet, this product oral, one time 3～5,3 times on the one; One after each meal.
Embodiments of the invention 2: Rhizoma Rodgersiae 445g, Herba Pyrolae 62.5g, Cornu Cervi Degelatinatum 7.5g
Get Rhizoma Rodgersiae, add 8 times of 80% alcohol reflux 3 times, 2 hours for the first time, second and third time each 1 hour, merge extractive liquid, filters, filtrate recycling ethanol and when being concentrated into 50 ℃ relative density be 1.20 clear paste, standby; Other gets Herba Pyrolae, the Cornu Cervi Degelatinatum pulverize separately becomes fine powder, with above-mentioned Rhizoma Rodgersiae clear paste mixing, add an amount of starch, with 70% ethanol and 1.2% soybean oil system soft material, the soft material that makes micropill mechanism ball, wet feed pushed the 0.8mm sieve aperture, the wet grain of strip cuts off round as a ball, 50～60 ℃ of drying and mouldings are crossed 16～20 mesh sieves and are selected ball or merge above-mentioned four kinds of clear paste, spray drying, wet-milling granulation molding, mould placed add the great achievement ball in the coating pan, medicated powder: water is 1: 1.5, and the coating pan rotating speed is 40r/min, capping, select ball, coating, 4%80W type Opadry is a coating material, the coating solution speed of spraying into is 150～180g/min, inlet temperature is for being controlled between 85～88 ℃, and pot body rotating speed is controlled at 4～6/min, promptly gets pellet.
Embodiments of the invention 3: Rhizoma Rodgersiae 445g, Herba Pyrolae 62.5g, Cornu Cervi Degelatinatum 7.5g
Get Rhizoma Rodgersiae, add 8 times of 80% alcohol reflux 3 times, 2 hours for the first time, second and third time each 1 hour, merge extractive liquid, filters, filtrate recycling ethanol and when being concentrated into 50 ℃ relative density be 1.20 clear paste, standby; Other gets Herba Pyrolae, the Cornu Cervi Degelatinatum pulverize separately becomes fine powder, with above-mentioned Rhizoma Rodgersiae clear paste mixing, add 10% sodium bicarbonate, 12% citric acid, 1% aspartame pulverize separately, with the medicated powder mix homogeneously, granulate, drying, tabletting, coating, coating material: internal layer uses PVP to add titanium dioxide, the outer acrylic resin II that uses, during 40 ℃ of sheet bed tempertaures, jet velocity 6.0ml/kgmin promptly gets effervescent tablet.
Embodiments of the invention 4: Rhizoma Rodgersiae 445g, Herba Pyrolae 62.5g, Cornu Cervi Degelatinatum 7.5g
Get Rhizoma Rodgersiae, add 8 times of 80% alcohol reflux 3 times, 2 hours for the first time, second and third time each 1 hour, merge extractive liquid, filters, filtrate recycling ethanol and when being concentrated into 50 ℃ relative density be 1.20 clear paste, standby; Other gets Herba Pyrolae, the Cornu Cervi Degelatinatum pulverize separately becomes fine powder, with above-mentioned Rhizoma Rodgersiae clear paste mixing, adds distilled water, promptly gets oral liquid.
Embodiments of the invention 5: Rhizoma Rodgersiae 445g, Herba Pyrolae 62.5g, Cornu Cervi Degelatinatum 7.5g
Get Rhizoma Rodgersiae, add 8 times of 80% alcohol reflux 3 times, 2 hours for the first time, second and third time each 1 hour, merge extractive liquid, filters, filtrate recycling ethanol and when being concentrated into 50 ℃ relative density be 1.20 clear paste, standby; Other gets Herba Pyrolae, the Cornu Cervi Degelatinatum pulverize separately becomes fine powder, with above-mentioned Rhizoma Rodgersiae clear paste mixing, adds carbomer, makes gel.
Embodiments of the invention 6: Rhizoma Rodgersiae 445g, Herba Pyrolae 62.5g, Cornu Cervi Degelatinatum 7.5g
Get Rhizoma Rodgersiae, add 8 times of 80% alcohol reflux 3 times, 2 hours for the first time, second and third time each 1 hour, merge extractive liquid, filters, filtrate recycling ethanol and when being concentrated into 50 ℃ relative density be 1.20 clear paste, standby; Other gets Herba Pyrolae, the Cornu Cervi Degelatinatum pulverize separately becomes fine powder, with above-mentioned Rhizoma Rodgersiae clear paste mixing, adds sodium carboxymethyl cellulose, and tabletting is made dispersible tablet.
Embodiments of the invention 7: the discriminating of Rhizoma Rodgersiae, Bergeninum in the capsule:
It is an amount of to get 'Yan Lu Ru Kang ' capsule 's content to be measured, therefrom takes by weighing 0.5g, adds ethanol 20ml, and ultrasonic 10 minutes, filter, filtrate is as need testing solution; The Rhizoma Rodgersiae medical material shines medical material solution in pairs with legal system; Other gets the Bergeninum reference substance, adds ethanol and makes the solution that every 1ml contains 2mg, in contrast product solution; According to the disclosed thin layer chromatography test of Chinese Pharmacopoeia appendix, draw each 10 μ l of need testing solution and reference substance solution, putting respectively on same silica gel g thin-layer plate, is developing solvent with dichloromethane-butyl acetate-formic acid (8: 4: 1), launches, take out, dry, put under the uviol lamp (365nm) and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
The discriminating of Rhizoma Rodgersiae in embodiment 8 micropills:
It is an amount of to get 'Yan Lu Ru Kang ' micropill to be measured, therefrom takes by weighing 0.6g, adds methanol 20ml, and warm macerating 10 minutes filters, and filtrate is as need testing solution; Rhizoma Rodgersiae medical material 0.5g shines medical material solution in pairs with legal system; According to the disclosed thin layer chromatography test of Chinese Pharmacopoeia appendix, draw each 5 μ l of need testing solution and reference substance solution, put in same silica gel G F respectively
254On the lamellae, be developing solvent, launch, take out, dry, put under the uviol lamp (254nm) and inspect with chloroform-butyl acetate-acetic acid (3: 7: 1), in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
The discriminating of Bergeninum in embodiment 9 tablets:
Get this product, porphyrize therefrom takes by weighing 0.4g, adds methanol 3ml, and jolting 30 minutes filters, and filtrate is as need testing solution.Other gets the Bergeninum reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.According to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2005 B) test, draw need testing solution 3 μ l, reference substance solution 10 μ l put in same silica gel G F respectively
254On the lamellae, be developing solvent, launch, take out, dry, put under the ultra-violet lamp (254nm) and inspect with chloroform-ethyl acetate-formic acid (5: 4: 2), in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
The assay of Bergeninum in embodiment 10 capsules:
It is an amount of to get 'Yan Lu Ru Kang ' capsule 's content to be measured, and mixing is therefrom got an amount of accurate the title and decided, and adds alcohol reflux and gets, and puts to room temperature, supplies the ethanol of loss, shakes up, and filters, and gets subsequent filtrate, as need testing solution; It is an amount of that precision takes by weighing the Bergeninum reference substance, puts in the brown measuring bottle, adds ethanol and make reference substance solution; With eight alkyl silane bonded silica gels is filler, acetonitrile-water (10: 90) is a mobile phase, the detection wavelength is 365nm, calculates with one point external standard method, and 'Yan Lu Ru Kang ' formulation content limit to be measured should be: one with containing Rhizoma Rodgersiae in the 'Yan Lu Ru Kang ' capsule with Bergeninum (C
14H
16O
9) meter, must not be less than 27mg.
The assay of Bergeninum in embodiment 11 micropills:
It is an amount of to get 'Yan Lu Ru Kang ' micropill content to be measured, and mixing is therefrom got an amount of accurate the title and decided, and adds the methanol supersound extraction, puts to room temperature, supplies the methanol of loss, shakes up, and filters, and gets subsequent filtrate, as need testing solution; It is an amount of that precision takes by weighing the Bergeninum reference substance, puts in the brown measuring bottle, adds methanol and make reference substance solution; With octadecylsilane chemically bonded silica is filler, acetonitrile-water (15: 85) is a mobile phase, the detection wavelength is 276nm, calculates with one point external standard method, and 'Yan Lu Ru Kang ' micropill content limit to be measured should be: one with containing Rhizoma Rodgersiae in the 'Yan Lu Ru Kang ' micropill with Bergeninum (C
14H
16O
9) meter, must not be less than 54mg.
The assay of Bergeninum in embodiment 12 tablets:
Get this product under the weight differential item, porphyrize is therefrom got about 0.4g, the accurate title, decide, and puts in the brown measuring bottle of 50ml, and it is an amount of to add methanol, supersound process (power 250W, frequency 33KHz) 40 minutes is taken out, put to room temperature, add methanol and be diluted to scale, shake up, filter with microporous filter membrane (0.45 μ m), get subsequent filtrate, as need testing solution; It is an amount of that other gets the Bergeninum reference substance, puts in the brown measuring bottle, adds methanol and make the solution that every 1ml contains 0.15mg, and product solution is filler with the octadecylsilane chemically bonded silica in contrast; With methanol-water (18: 82) is mobile phase; The detection wavelength is 275nm.Number of theoretical plate calculates by the Bergeninum peak should be not less than 2000.Accurate respectively reference substance solution and each 5 μ l of need testing solution of drawing inject chromatograph of liquid, measure, promptly.Calculate with one point external standard method, one with containing Rhizoma Rodgersiae in the 'Yan Lu Ru Kang ' micropill with Bergeninum (C
14H
16O
9) meter, must not be less than 54mg.
Claims (10)
1. YANLU RUKANG YAOWU ZHIJI for the treatment of cyclomastopathy is characterized in that: it mainly is made into effervescent tablet, injection, powder pin, freeze-dried powder, gel, dispersible tablet, capsule, soft capsule, microcapsule, granule, pill, micropill, powder, drop pill, slow releasing preparation, controlled release preparation, gel, oral liquid, soft extract, extractum or membrane by Rhizoma Rodgersiae 445g, Herba Pyrolae 62.5g, Cornu Cervi Degelatinatum 7.5g or with their extract of corresponding weight portion.
2. according to the YANLU RUKANG YAOWU ZHIJI of the described treatment cyclomastopathy of claim 1, it is characterized in that: described preparation is tablet, granule or pellet.
3. the preparation method of the YANLU RUKANG YAOWU ZHIJI of treatment cyclomastopathy as claimed in claim 1 or 2, it is characterized in that: get Rhizoma Rodgersiae, add 8 times of alcohol refluxs 3 times, 2 hours for the first time, second and third time each 1 hour, merge extractive liquid, filters, filtrate recycling ethanol and when being concentrated into 50 ℃ relative density be 1.20 clear paste, standby; Other gets Herba Pyrolae, the Cornu Cervi Degelatinatum pulverize separately becomes fine powder, with above-mentioned Rhizoma Rodgersiae clear paste mixing, makes different preparations then respectively.
4. according to the preparation method of the YANLU RUKANG YAOWU ZHIJI of the described treatment cyclomastopathy of claim 3, it is characterized in that: the tablet in the described preparation prepares like this: get Rhizoma Rodgersiae, add 8 times of alcohol refluxs 3 times, 2 hours for the first time, second and third time each 1 hour, merge extractive liquid, filters, filtrate recycling ethanol and when being concentrated into 50 ℃ relative density be 1.20 clear paste, standby; Other gets Herba Pyrolae, the Cornu Cervi Degelatinatum pulverize separately becomes fine powder, with above-mentioned Rhizoma Rodgersiae clear paste mixing, adds appropriate amount of starch, 4% Pulvis Talci and 5% microcrystalline Cellulose, and drying is pulverized, sieve, and tabletting, coating, coating material are Opadry 2, consumption is 6%, promptly.
5. according to the preparation method of the YANLU RUKANG YAOWU ZHIJI of the described treatment cyclomastopathy of claim 3, it is characterized in that: the pellet in the described preparation prepares like this: get Rhizoma Rodgersiae, add 8 times of alcohol refluxs 3 times, 2 hours for the first time, second and third time each 1 hour, merge extractive liquid, filters, filtrate recycling ethanol and when being concentrated into 50 ℃ relative density be 1.20 clear paste, standby; Other gets Herba Pyrolae, the Cornu Cervi Degelatinatum pulverize separately becomes fine powder, with above-mentioned Rhizoma Rodgersiae clear paste mixing, add an amount of starch, with 70% ethanol and 1.2% soybean oil system soft material, the soft material that makes micropill mechanism ball, wet feed pushed the 0.8mm sieve aperture, the wet grain of strip cuts off round as a ball, 50～60 ℃ of drying and mouldings are crossed 16～20 mesh sieves and are selected ball or merge above-mentioned four kinds of clear paste, spray drying, wet-milling granulation molding, mould placed add the great achievement ball in the coating pan, medicated powder: water is 1: 1.5, and the coating pan rotating speed is 40r/min, capping, select ball, coating, 4%80W type Opadry is a coating material, the coating solution speed of spraying into is 150～180g/min, inlet temperature is for being controlled between 85～88 ℃, and pot body rotating speed is controlled at 4～6/min, promptly.
6. the method for quality control of the YANLU RUKANG YAOWU ZHIJI of treatment cyclomastopathy as claimed in claim 1 or 2 is characterized in that: this method comprises following all or part of content:
(1) all or part of differential test method in Rhizoma Rodgersiae, the Bergeninum;
(2) content test method of Bergeninum.
7. by the method for quality control of the described 'Yan Lu Ru Kang ' preparation of claim 6, it is characterized in that: the discrimination method of described preparation comprises one or both discriminating in Rhizoma Rodgersiae, the Bergeninum:
It is an amount of to get 'Yan Lu Ru Kang ' preparation content to be measured, adds methanol or ethanol extraction, filters, and filtrate is as need testing solution; Get the Rhizoma Rodgersiae control medicinal material, shine medical material solution in pairs with legal system; Get the Bergeninum reference substance, add methanol or dissolve with ethanol, make reference substance solution, draw need testing solution and reference substance solution 1～30 μ l, put respectively on same silica gel G F25 lamellae or silica gel g thin-layer plate or silica gel H lamellae, with chloroform or dichloromethane-ethyl acetate or Ethyl formate or butyl acetate-formic acid or acetic acid=1～5: be developing solvent at 1～4: 0～2, launch, take out, dry, put under the uviol lamp and inspect, in the test sample chromatograph, with control medicinal material or the corresponding position of reference substance chromatograph on, show the speckle of same color.
8. by the method for quality control of the described 'Yan Lu Ru Kang ' preparation of claim 7, it is characterized in that: the discrimination method of described preparation comprises one or both discriminating in Rhizoma Rodgersiae, the Bergeninum:
It is an amount of to get 'Yan Lu Ru Kang ' preparation content to be measured, therefrom takes by weighing 0.4g, adds methanol 3ml, and jolting 30 minutes filters, and filtrate is as need testing solution; The Rhizoma Rodgersiae medical material shines medical material solution in pairs with legal system; Other gets the Bergeninum reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; Draw need testing solution 3 μ l, reference substance or control medicinal material solution 10 μ l, putting respectively on same silica GF254 lamellae, is developing solvent with chloroform-ethyl acetate-formic acid=5: 4: 2, launches, take out, dry, put under the uviol lamp of 254nm and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
9. by the method for quality control of the described 'Yan Lu Ru Kang ' preparation of claim 6, it is characterized in that: the content assaying method of described preparation is the assay of Bergeninum:
It is an amount of to get 'Yan Lu Ru Kang ' preparation content to be measured, and mixing is therefrom got an amount of accurate the title and decided, and adds methanol or ethanol extraction, puts to room temperature, supplies the methanol or the ethanol of loss, shakes up, and filters, and gets subsequent filtrate, as need testing solution; It is an amount of that precision takes by weighing the Bergeninum reference substance, puts in the brown measuring bottle, adds methanol or ethanol is made reference substance solution; With octadecylsilane chemically bonded silica or eight alkyl silane bonded silica gels or dialkyl silane bonded silica gel is filler, and methanol or acetonitrile-water=5～30: 60～95 is mobile phase, detects wavelength and be among 190～410nm one or several; Calculate with standard curve method or one point external standard method, 'Yan Lu Ru Kang ' formulation content limit to be measured should be: must not be less than 27mg with containing Rhizoma Rodgersiae in the 'Yan Lu Ru Kang ' preparation in Bergeninum: C14H16O9 on 1st.
10. by the method for quality control of the described 'Yan Lu Ru Kang ' preparation of claim 9, it is characterized in that: the content assaying method of described preparation is the assay of Bergeninum:
It is an amount of to get 'Yan Lu Ru Kang ' preparation content to be measured, and mixing is therefrom got about 0.4g, the accurate title, decide, and puts in the brown measuring bottle of 50ml, and it is an amount of to add methanol, at power is 250W, and frequency is a supersound process 40 minutes under the 33KHz, takes out, put to room temperature, add methanol and be diluted to scale, shake up, with the microporous filter membrane filtration of 0.45 μ m, get subsequent filtrate, as need testing solution; It is an amount of that precision takes by weighing the Bergeninum reference substance, puts in the brown measuring bottle, adds methanol and make the solution that every 1ml contains 0.15mg, in contrast product solution; With octadecylsilane chemically bonded silica is filler, and methanol-water=18: 82 is a mobile phase, and the detection wavelength is 275nm; Calculate with one point external standard method, 'Yan Lu Ru Kang ' formulation content limit to be measured should be: must not be less than 54mg with containing Rhizoma Rodgersiae in the 'Yan Lu Ru Kang ' preparation in Bergeninum: C14H1609 on 1st.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104483432A (en) * | 2014-12-24 | 2015-04-01 | 昆明振华制药厂有限公司 | Medicine quality detection method for compound bergenin tablets |
| CN104597196A (en) * | 2015-01-09 | 2015-05-06 | 山东东阿阿胶股份有限公司 | Method for identifying Japanese ardisia herb in Chinese patent medicine for treating heat asthma |
| CN105769942A (en) * | 2014-12-22 | 2016-07-20 | 贵州益佰女子大药厂有限责任公司 | Yanlu breast health preparation and preparation method thereof |
| CN106680414A (en) * | 2013-07-26 | 2017-05-17 | 九芝堂股份有限公司 | Detection method of compound ardisia japonica tablet |
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2006
- 2006-05-09 CN CN2006102004252A patent/CN1876000B/en active Active
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106680414A (en) * | 2013-07-26 | 2017-05-17 | 九芝堂股份有限公司 | Detection method of compound ardisia japonica tablet |
| CN105769942A (en) * | 2014-12-22 | 2016-07-20 | 贵州益佰女子大药厂有限责任公司 | Yanlu breast health preparation and preparation method thereof |
| CN105769942B (en) * | 2014-12-22 | 2019-06-18 | 贵州益佰女子大药厂有限责任公司 | A kind of 'Yan Lu Ru Kang ' preparation and preparation method thereof |
| CN104483432A (en) * | 2014-12-24 | 2015-04-01 | 昆明振华制药厂有限公司 | Medicine quality detection method for compound bergenin tablets |
| CN104597196A (en) * | 2015-01-09 | 2015-05-06 | 山东东阿阿胶股份有限公司 | Method for identifying Japanese ardisia herb in Chinese patent medicine for treating heat asthma |
| CN104597196B (en) * | 2015-01-09 | 2016-05-25 | 山东东阿阿胶股份有限公司 | Treat the discrimination method of ardisia japonica in the Chinese patent drug of hot heavy breathing disease |
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