CN1899397A - Heart activating oral disintergration tablet and its preparing method - Google Patents
Heart activating oral disintergration tablet and its preparing method Download PDFInfo
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- CN1899397A CN1899397A CNA2005100870212A CN200510087021A CN1899397A CN 1899397 A CN1899397 A CN 1899397A CN A2005100870212 A CNA2005100870212 A CN A2005100870212A CN 200510087021 A CN200510087021 A CN 200510087021A CN 1899397 A CN1899397 A CN 1899397A
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Abstract
The present invention discloses a kind of heart activating oral disintegrant tablet and its preparation process. The preparation process of the heart activating oral disintegrant tablet includes: extracting musk and toad cake; coating the musk and toad cake extract and bear bile with beta-cyclodextrin; mixing the coated matters with medicine powder of glossy ganoderma, safflower extract, aconite root extract, ginseng extract, bezoar and pearl; adding medicinal supplementary material in optimal ratio; and preparing the oral disintegrant tablet. The heart activating oral disintegrant tablet has high pharmaceutical effect.
Description
Technical field
The invention belongs to technical field of Chinese medicines, be specifically related to a kind of heart activating oral disintergration tablet and preparation method thereof.
Technical background
Pill for promoting coronary circulation records in the 18 in " The People's Republic of China's the Sanitation Ministry medicine standard " Chinese traditional patent formulation preparation; be to be the Chinese medicine preparation that raw material is made with Ganoderma, Moschus, Fel Ursi, Flos Carthami, Calculus Bovis, Margarita, Radix Ginseng, Venenum Bufonis, Radix Aconiti Lateralis Preparata, Borneolum Syntheticum; has benefiting QI for activating blood circulation; the effect of warming the meridian and promoting blood circulation; cure mainly the thoracic obstruction, pained, be used for coronary heart disease, angina pectoris.Studies show that " pill for promoting coronary circulation " has obvious allevating angina pectoris, the effect that resists myocardial ischemia.
Pill for promoting coronary circulation is a water pill, because preparation method and dosage form, the effective ingredient stripping is poor, bioavailability is low, can not guarantee the stable and controllable of medication, and is slow for acute angina pectoris and coronary heart disease its disintegration time of acute stage, thereby onset is slow, does not have the effect of first aid.Because Venenum Bufonis has zest, after the patient is oral, oral cavity stomach function regulating intestinal is had stimulation; The main effective ingredient Borneolum Syntheticum of Borneolum Syntheticum, the main effective ingredient muscone in the Moschus all have very strong volatility, and permanent storage can make drug effect reduce, and Fel Ursi has very heavy bitter off-flavors, and big to GI irritation.
Oral cavity disintegration tablet is meant not to be needed water or only need use low amounts of water, need not to chew, and tablet places lingual surface, meets after saliva separates rapidly or collapse, and borrows and swallows power, and medicine can be gone into the tablet of stomach onset.Its a kind of new pharmaceutical preparation, it can absorb through hypoglossis mucous membrane, directly enters blood, avoided first pass effect effectively, so taking dose is little, safety is good, and the oral cavity disintegration tablet disintegrate is fast, and therefore effect just progressively becomes the focus that pharmaceutical manufacturer and research and development field are paid close attention to rapidly.
This dosage form mainly is to select suitable fast disintegrant, can not need the water assisting deglutition when taking, and can rapid disintegrate become fine grained in the oral cavity, and only several swallowing acts can be finished drug administration process.Its more common solid orally ingestible absorbs fast, bioavailability height, and taking convenience.The preparation oral cavity disintegration tablet will be considered the problem of following critical aspects: 1, the advantage of oral cavity disintegration tablet just is rapid disintegrate, the release medicine is fast, reach rapid-action effect, seek suitable disintegrants, to guarantee oral cavity disintegration tablet disintegrate rapidly in the oral cavity, especially for Chinese medicine, because complicated component, and what have contains the bigger extractum of toughness, and this selection just seems and is even more important; 2, only need the just disintegrate fully of water of minute quantity owing to disintegrating tablet, therefore must consider stability, prolongation shelf life and the shelf-life of humidity environment oral cavity disintegration tablet higher relatively in the process of storage, significant to medical manufacturing enterprise.When the preparation oral cavity disintegration tablet, different principal agents mixes the ratio that a kind of the best is all arranged with pharmaceutic adjuvant, the oral cavity disintegration tablet disintegration rate for preparing under this optimal proportion is fast, pharmacological action is good, therefore, must be when the preparation oral cavity disintegration tablet according to the chemical property and the physical property of principal agent (effective ingredient in Chinese), determine the ratio of suitable pharmaceutic adjuvant and pharmaceutic adjuvant, make oral cavity disintegration tablet meet the characteristics of this dosage form, do not strengthen patient's dose again, so, we are when research heart activating oral disintergration tablet preparation process, determine a kind of ratio of the best, i.e. the ratio of principal agent and pharmaceutic adjuvant, and the optimal proportion of disintegrating agent etc. in the pharmaceutic adjuvant.
In patent retrieval, find no any report that closes heart activating oral disintergration tablet.
Summary of the invention
The present invention is according to the chemical property of each medicine in the preparation, Ganoderma, Flos Carthami, Radix Aconiti Lateralis Preparata, Radix Ginseng, Moschus, Venenum Bufonis are extracted, then Moschus, Venenum Bufonis extract, Borneolum Syntheticum, Fel Ursi have been carried out enclose with beta-schardinger dextrin-, reduced Borneolum Syntheticum, muscone volatility, the stability of these volatile effective components is increased, the zest of Venenum Bufonis is reduced, toxicity reduces, clathrate has been covered the bitter off-flavors of Fel Ursi, has alleviated the GI irritation of Fel Ursi.We are in a large amount of experimentations; chemical property and physical property according to the heart activating oral disintergration tablet contained drug; we have further done a large amount of experiments; determine the optimal proportion of principal agent of the present invention and pharmaceutic adjuvant; principal agent of the present invention (effective ingredient) with the pharmaceutic adjuvant optimal proportion is: principal agent (effective ingredient) is 40%-44%; pharmaceutic adjuvant is 56%-60%; wherein filler is 38%-43%; disintegrating agent is 14%-16%; correctives is 1%-2%; lubricant is 1%-3%; wherein principal agent (effective ingredient) weight portion composition is by Ganoderma among the present invention; Flos Carthami extract; Radix Aconiti Lateralis Preparata extract; Radix Ginseng extract; Calculus Bovis; drug powder 6-15 part and Moschus that crushing pearl obtains; Venenum Bufonis extract; Fel Ursi; Benexate Hydrochloride 27-40 part of Borneolum Syntheticum is formed; the heart activating oral disintergration tablet for preparing under this ratio meets the requirement of oral cavity disintegration tablet fully; disintegration rate is fast; the effective ingredient dissolution rate of principal agent is fast, has great pharmacological effects, especially is fit to the treatment acute coronary; the first aid of angina pectoris attacks etc.
The purpose of this invention is to provide a kind of taking convenience, rapid-action, bioavailability is high, curative effect is obvious, the heart activating oral disintergration tablet of preparation stabilization.
Another object of the present invention provides the preparation method of heart activating oral disintergration tablet.
The present invention is achieved through the following technical solutions:
One, process recipes
(1) the crude drug weight proportion is: Ganoderma 100-300 part, Moschus 3-8 part, Fel Ursi 3-8 part, Flos Carthami 50-200 part, Calculus Bovis 3-8 part, Margarita 3-8 part, Radix Ginseng 100-300 part, Venenum Bufonis 50-200 part, Radix Aconiti Lateralis Preparata 50-200 part, Borneolum Syntheticum 3-8 part;
(2) Ganoderma, Flos Carthami are decocted with water secondary, 1.5 hours for the first time, 1 hour for the second time, decoction liquor filtered, and merged, concentrate and vacuum drying, get Ganoderma, Flos Carthami extract, the 80-90% alcohol reflux of Radix Aconiti Lateralis Preparata usefulness pH2-3 2 times, merge extractive liquid,, decompression recycling ethanol also concentrates, and gets Radix Aconiti Lateralis Preparata extract; Radix Ginseng 40-60% alcohol reflux 3 times, the merging backflow filters, and filtrate concentrates and drying, gets Radix Ginseng extract; Merge Ganoderma, Flos Carthami extract, Radix Aconiti Lateralis Preparata extract, Radix Ginseng extract and Calculus Bovis, Margarita are pulverized, and get drug powder.
(3) get Moschus, Venenum Bufonis and doubly measure 70-80% ethanol with 8-12 and leach, leachate filters, and decompression recycling ethanol also concentrates; Fel Ursi, Borneolum Syntheticum dissolve with small amount of ethanol; The ethanol liquid of Fel Ursi, Borneolum Syntheticum is joined in above-mentioned Moschus, the Venenum Bufonis extracting solution; Slowly join 8-15 and doubly measure in the saturated aqueous solution of beta-schardinger dextrin-, 50 ℃ were stirred 2-4 hour, continued under the room temperature to stir 2 hours, and cold preservation is spent the night, and filters, and cold drying obtains clathrate;
(4) said medicine powder, clathrate and pharmaceutic adjuvant are mixed in proportion, granulation, drying, granulate, tabletting, check, packing obtain oral cavity disintegration tablet.
Disintegrating agent is one or both the mixture in low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, crospolyvinylpyrrolidone, the crosslinked carboxymethyl fecula sodium.
Filler is for being microcrystalline Cellulose.
Lubricant is a kind of in magnesium stearate, Pulvis Talci, the sodium lauryl sulphate.
Two, the preliminary of principal agent and pharmaceutic adjuvant ratio determined
Character and preliminary trial test result according to this preparation Chinese medicine powder and clathrate, when we determine pharmaceutic adjuvant proportion 0-40%, molding effect is poor, can not prepare tablet, the pharmaceutic adjuvant amount was greater than 60% o'clock, the adjuvant amount of required usefulness is many, and owing to the deliquescent reason of adjuvant can influence mouthfeel, therefore, we determine that tentatively the pharmaceutic adjuvant ratio is that 40%-60% experimentizes, to obtain optimal proportion, according to the trial test result, we are by the pharmaceutic adjuvant of different proportion, and different proportion such as disintegrating agent experimentizes in the pharmaceutic adjuvant, mainly investigates experiment by the disintegrating agent performance to oral cavity disintegration tablet.
Determining of experimental program:
Scheme 1: principal agent accounts for 60%, and pharmaceutic adjuvant accounts for 40%, and wherein filler is 24%, and disintegrating agent is 14%, and correctives 1%, lubricant are 1%.
Scheme 2: principal agent accounts for 60%, and pharmaceutic adjuvant accounts for 40%, and wherein filler is 22%, and disintegrating agent is 16%, and correctives 1%, lubricant are 1%.
Scheme 3: principal agent accounts for 50%, and pharmaceutic adjuvant accounts for 50%, and wherein filler is 33%, and disintegrating agent is 14%, and correctives 1%, lubricant are 2%.
Scheme 4: principal agent accounts for 40%, and pharmaceutic adjuvant accounts for 60%, and wherein filler is 41%, and disintegrating agent is 16%, and correctives 1%, lubricant are 2%.
Experimental technique one:
(1) solubility experiment: the saturated aqueous solution at 37 ℃ of preparation samples, utilize membrane filter to filter, obtain filtrate, the filtrate of predetermined of accurately weighing is utilized the freeze-drying drying, thereby is obtained the content of water, calculate water-soluble on the water content basis that obtains thus again, the results are shown in Table 1.
(2) viscosity experiment: the saturated aqueous solutions at 37 ℃ of different disintegrating agents of preparation, utilize membrane filter to filter, obtain filtrate, utilize viscometer to obtain filtrate 37 ℃ viscosity, the results are shown in Table 1.
(3) measurement of wettability: precision takes by weighing above-mentioned oral cavity disintegration tablet, dry weighs fully, is put into 1 week under 25 ℃ and 75% the damp condition, takes by weighing weight, and calculating wettability (%) sees Table 1.
(4) volume increases percent: the volume of moisture absorption fore-and-aft survey disintegrating agent, calculate the percent (%) of the volume increase of oral cavity disintegration tablet, and see Table 1.
Table 1 disintegrating agent performance is investigated relatively
| Group | Dissolubility (37 ℃) W/V | Viscosity (37 ℃) mpa.s | Wettability % | Volume increases percent % |
| Scheme 1 scheme 2 schemes 3 schemes 4 | 35 40 42 43 | 2.9 3.1 3.4 3.2 | 2.20 1.60 0.60 0.50 | 1.80 1.10 0.25 0.20 |
Experimental technique two:
(1) hardness of mensuration tablet: utilize the tablet hardness analyzer to measure the hardness of tablet, the results are shown in Table 2.
(2) stability experiment: tablet is put into 12 weeks under 25 ℃ and 75% the damp condition, observes the tablet spoilage, the results are shown in Table 2.
(3) disintegrate experiment: according to the disintegration of tablet method of testing of stipulating in the Pharmacopoeia of People's Republic of China, utilize the disintegrate tester to measure, the results are shown in Table 2.
(4) disintegrate test in the oral cavity, disintegration time, grittiness, taste to three health adults have tested experimental group the results are shown in Table 2.
Table 2 disintegrating property is investigated
| Experimental group | Hardness (kg) | Spoilage (%) | Disintegration time (s) | The Orally disintegrating time (s) | Grittiness | Taste |
| Scheme 1 scheme 2 schemes 3 schemes 4 | 4.0 4.1 3.6 3.5 | 18.7 17.0 5.0 4.0 | 45.0 42.0 21.0 20.0 | 55.0 52.0 25.0 24.0 | Having does not seldom have | General better good |
We carry out a series of variations with disintegrating agent, filler, lubricant, correctives ratio in experimental program 1, scheme 2 pharmaceutic adjuvants, and experimental result changes little.
Experimental analysis: by experiment one we analyze, it is bigger that scheme 1, scheme 2 wettabilities, volume increase percentage ratio, by experiment two we analyze scheme 1, scheme 2 spoilages are bigger, this result bigger with testing a wettability is consistent, and the disintegration time of scheme 1, scheme 2 is too slow, and taste does not meet the requirement of oral cavity disintegration tablet yet.
Experiment conclusion: by the experiment of above-mentioned disintegrating property, we determine that the ratio of pharmaceutic adjuvant of the present invention is 50%-60%.
Three, principal agent and pharmaceutic adjuvant optimal proportion are determined
According to the PRELIMINARY RESULTS of test two, we carry out disintegration experiment, dissolution experiment to the heart activating oral disintergration tablet of different proportion, further determine principal agent and pharmaceutic adjuvant optimal proportion.
According to experiment two the experimental program scheme determination that experimentizes.
Scheme 1: principal agent accounts for 40%, and pharmaceutic adjuvant accounts for 60%, and wherein filler is 46%, and disintegrating agent is 12%, and correctives 1%, lubricant are 1%.
Scheme 2: principal agent accounts for 40%, and pharmaceutic adjuvant accounts for 60%, and wherein filler is 43%, and disintegrating agent is 14%, and correctives 2%, lubricant are 1%.
Scheme 3: principal agent accounts for 42%, and pharmaceutic adjuvant accounts for 58%, and wherein filler is 38%, and disintegrating agent is 16%, and correctives 1%, lubricant are 3%.
Scheme 4: principal agent accounts for 42%, and pharmaceutic adjuvant accounts for 58%, and wherein filler is 38%, and disintegrating agent is 18%, and correctives 1%, lubricant are 1%.
Scheme 5: principal agent accounts for 44%, and pharmaceutic adjuvant accounts for 56%, and wherein filler is 35%, and disintegrating agent is 18%, and correctives 2%, lubricant are 1%.
Scheme 6: principal agent accounts for 44%, and pharmaceutic adjuvant accounts for 56%, and wherein filler is 40%, and disintegrating agent is 14%, and correctives 1%, lubricant are 1%.
Scheme 7: principal agent accounts for 46%, and pharmaceutic adjuvant accounts for 54%, and wherein filler is 39%, and disintegrating agent is 12%, and correctives 1%, lubricant are 2%.
Scheme 8: principal agent accounts for 46%, and pharmaceutic adjuvant accounts for 54%, and wherein filler is 36%, and disintegrating agent is 14%, and correctives 2%, lubricant are 2%.
Scheme 9: principal agent accounts for 48%, and pharmaceutic adjuvant accounts for 52%, and wherein filler is 34%, and disintegrating agent is 12%, and correctives 3%, lubricant are 3%.
Scheme 10: principal agent accounts for 48%, and pharmaceutic adjuvant accounts for 52%, and wherein filler is 28%, and disintegrating agent is 16%, and correctives 4%, lubricant are 4%.
Scheme 11: principal agent accounts for 50%, and pharmaceutic adjuvant accounts for 50%, and wherein filler is 35%, and disintegrating agent is 12%, and correctives 1%, lubricant are 2%.
Scheme 12: principal agent accounts for 50%, and pharmaceutic adjuvant accounts for 50%, and wherein filler is 28%, and disintegrating agent is 18%, and correctives 1%, lubricant are 3%.
1. disintegration: get above-mentioned heart activating oral disintergration tablet, place the beaker of the 10ml that fills 37 ℃ of water of 5ml, stir, calculate whole disintegrates and the required time by No. 2 sieves with 30 rev/mins speed.The results are shown in Table 3;
2. dissolution experiment
2.1. instrument and the full-automatic digestion instrument of reagent SR-6 type (U.S. Hanson company); Distilled water (self-control); Oral cavity disintegration tablet (Tianzhijiao Medication Development Co., Ltd., Guangdong's laboratory provides) according to each experimental program preparation;
2.2 the dissolution experimental technique of Borneolum Syntheticum: press in the dissolution method (" two appendix XC of Chinese pharmacopoeia version in 2000) three therapeutic methods of traditional Chinese medicine and measure.With 0.1mol/LHCL solution 300ml is dissolution medium, heat and make water temperature remain on 37 ℃ ± 0.5 ℃, rotating speed of agitator is 100 rev/mins, put into 1 of pill for promoting coronary circulation 1 ball of the present invention or heart activating oral disintergration tablet, filter sampling respectively at setting-up time through 0.8 μ m microporous filter membrane in confined conditions, sampling amount is 1.0ml, adds equivalent 1.0ml isothermal medium simultaneously.The accurate sample solution 0.7ml that draws, accurate ethyl acetate solution (0.02mg/ml) 0.3ml that adds naphthalene, vortex mixing 5min, centrifugal 10min, drawing supernatant 1 μ l measures, record and compute effective ingredient no longer the time of stripping be the time of whole strippings, the content assaying method of Borneolum Syntheticum is with reference to " the Borneolum Syntheticum content assaying method is measured under Borneolum Syntheticum item of Chinese pharmacopoeia version in 2000.The results are shown in Table 3.
2.3 the assay method of Radix Ginseng total saponins: get an amount of porphyrize of formulation samples, get powder (pill 225mg, tablet 2.0g), the accurate title, decide, add dehydrated alcohol 100ml, supersound process 30min filters, and adding kieselguhr was mixed thoroughly when filtrate was steamed to about 5ml, evaporate to dryness, put and use chloroform reflux defat 2h in the apparatus,Soxhlet's, an interior again methanol eddy extracts 5h, and it is extremely dried to reclaim methanol, residue adds in aluminium oxide-D101 macroporous resin column of having handled well with the suitable quantity of water dissolving, 70% ethanol elution is being used in water flushing back, collects eluent, evaporate to dryness, residue adds dissolve with methanol and quantitatively is transferred in the 10ml measuring bottle, and be diluted to scale, and shake up, make need testing solution.Prepare negative control solution by the need testing solution preparation method, the accurate need testing solution 50 μ L that draw place tool plug test tube, and low temperature is flung to solvent, adds 5% vanillin-glacial acetic acid solution 0.2ml, perchloric acid 0.8ml, in 60 ℃ of insulations of water-bath 15min, take out, put and cool off 2-3min in the ice bath, add glacial acetic acid 5ml again, shake up, adding retinue reagent with negative control solution is the blank absorbance of measuring at the 560nm place, calculates its content.
2.4 Radix Ginseng total saponins dissolution determination method: press in the dissolution method (" two appendix XC of Chinese pharmacopoeia version in 2000) three therapeutic methods of traditional Chinese medicine and measure.With distilled water 300ml is dissolution medium, heat and make water temperature remain on 37 ℃ ± 0.5 ℃, rotating speed of agitator is 100 rev/mins, put into 1 of pill for promoting coronary circulation 1 ball of the present invention or heart activating oral disintergration tablet, filter sampling respectively at setting-up time through 0.8 μ m microporous filter membrane, sampling amount is 2.0ml, adds equivalent 2.0ml isothermal medium simultaneously.The accurate sample solution 2.0ml that draws, with 10ml chloroform extraction 3 times, discard chloroform solution, aqueous solution was added in aluminium oxide-D101 macroporous resin column of handling, and 70% ethanol elution is being used in water flushing back, collects eluent, evaporate to dryness, assay method according to Radix Ginseng total saponins is measured, record and calculate effective ingredient no longer the time of stripping be the time of whole strippings, the results are shown in Table 3.
Table 3 disintegration, whole dissolution time are relatively
| Group | The time (second) of whole disintegrates | The time of the whole strippings of Borneolum Syntheticum | The time of the whole strippings of Radix Ginseng total saponins (branch) |
| Scheme 1 scheme 2 schemes 3 schemes 4 schemes 5 schemes 6 schemes 7 schemes 8 schemes 9 schemes 10 schemes 11 schemes 12 | 32.2 22.1 21.5 27.9 27.5 21.6 29.3 27.7 30.2 29.1 29.7 28.5 | 13.8 7.5 7.4 10.1 10.5 7.8 13.0 12.5 13.5 11.8 12.5 11.6 | 9.1 5.2 4.9 8.5 8.9 5.4 9.9 9.4 10.2 9.6 9.9 9.4 |
Conclusion: by above-mentioned experiment, determine that the optimal proportion of principal agent of the present invention and pharmaceutic adjuvant is: principal agent 40%-44%, pharmaceutic adjuvant are 56%-60%, wherein disintegrating agent is that filler is 38%-43%, and disintegrating agent is 14%-16%, correctives is 1%-2%, and lubricant is 1%-3%.Experiment finds that also the ratio of principal agent Central Plains medicated powder and clathrate influences smaller to above result.
Four, with the comparison of pill for promoting coronary circulation dissolution
Reagent: pill for promoting coronary circulation (Guangzhou Baiyunshan Pharmaceutical Co); Oral cavity disintegration tablet of the present invention (, providing) by Tianzhijiao Medication Development Co., Ltd., Guangdong's laboratory by the inventive method preparation;
Experimental technique: measuring by above-mentioned dissolution determination method, is 100% with the Borneolum Syntheticum actual content of Borneolum Syntheticum in the sample, calculates the accumulative total stripping percentage rate of Borneolum Syntheticum.With Radix Ginseng total saponins actual content in the sample is 100%, calculates the accumulative total stripping percentage rate of Radix Ginseng total saponins.The result sees Table 4 respectively, table 5.
The dissolution experiment of table 4 heart preparation alive Borneolum Syntheticum
| Medicine | Sample time (min) | |||||||
| 0.5 | 1 | 2 | 4 | 8 | 15 | 20 | 40 | |
| Pill for promoting coronary circulation oral cavity disintegration tablet of the present invention | 4.2 51.0 | 6.8 76.5 | 11.9 87.0 | 18.5 99.2 | 28.3 100.2 | 37..4 100.3 | 51.0 100.1 | 64.2 99.7 |
The dissolution experiment of table 5 heart preparation alive Radix Ginseng total saponins
| Medicine | Sample time (min) | |||||||
| 0.5 | 1 | 2 | 4 | 8 | 15 | 20 | 40 | |
| Pill for promoting coronary circulation oral cavity disintegration tablet of the present invention | 1.2 75.8 | 10.5 81.9 | 17.5 93.8. | 27.3 98.7 | 44.9 101.5 | 69.5 100.4 | 76.6 99.9 | 83.5 99.5 |
Conclusion: with Borneolum Syntheticum and Radix Ginseng total saponins is index, adopt the heart activating oral disintergration tablet dissolution rate of the inventive method preparation obviously faster, wherein Borneolum Syntheticum 1min stripping can reach 76.5%, and Radix Ginseng total saponins 0.5min stripping can reach 75.8%, and the pill for promoting coronary circulation stripping is obviously slower.Therefore, it is faster that heart activating oral disintergration tablet of the present invention and pill for promoting coronary circulation relatively have a stripping, and produce effects is characteristics more rapidly.
Five, preparation stability test
Pill for promoting coronary circulation and heart activating oral disintergration tablet of the present invention have been carried out the long-time stability comparative test, measure the content of Borneolum Syntheticum and muscone in 0 month, June, December, 18 months, 24 months preparations respectively, and the assay method reference literature of Borneolum Syntheticum [content of Borneolum Syntheticum in the gas chromatography determination Heart pill of Musk. " Chinese pharmacist "; 6,1999:317] method measures, and the assay method of muscone is with reference to " content assaying method under 2000 editions Moschus items of Chinese pharmacopoeia is 100% in 0 month content, the results are shown in Table 6 and table 7.
Table 6 long-time stability content of bornyl alcohol (%)
| Group | 0 month | June | December | 18 months | 24 months |
| Pill for promoting coronary circulation oral cavity disintegration tablet of the present invention | 100 100 | 95.7 99.9 | 92.7 99.6 | 90.5 99.2 | 86.5 98.3 |
Table 7 long-time stability muscone content (%)
| Group | 0 month | June | December | 18 months | 24 months |
| Pill for promoting coronary circulation oral cavity disintegration tablet of the present invention | 100 100 | 96.9 99.7 | 93.5 99.1 | 91.2 98.5 | 88.7 97.2 |
By above experimental result as can be known, adopt the heart activating oral disintergration tablet of the present invention's preparation, because volatility has partly been carried out enclose, its stability significantly improves, 24 months Borneolum Syntheticums of long-time stability experiments and the basic no change of muscone content, and Borneolum Syntheticum and muscone content all have reduction slightly in the pill for promoting coronary circulation, prove absolutely that technology of the present invention is more scientific and reasonable.
Six, pharmacology embodiment
Reagent and animal: pill for promoting coronary circulation (Guangzhou Baiyunshan Pharmaceutical Co); Oral cavity disintegration tablet of the present invention (, providing) by Tianzhijiao Medication Development Co., Ltd., Guangdong's laboratory by the inventive method preparation; New zealand rabbit: body weight 2.2-2.8kg; The Beagle Canis familiaris L., body weight 7.5-10kg, white mice, body weight 18-22g.
1. to the influence of rabbit acute myocardial ischemia
30 of new zealand rabbits, male and female are regardless of, body weight 2.2kg-2.8kg, be divided into 6 groups, adopt pentobarbital sodium anesthesia (30mg/kg) intravenous anesthesia, conventional tracheal intubation, recording respiration frequency, subintegumental electrode guiding electrocardio, through leading instrument (RM6000) recorded heart rate and electrocardiogram more, and via the SMOP-PC versatile interface, record R-R interval the line frequency analysis of spectrum of going forward side by side, write down rabbit respectively just often, (injection of pituitrin ADH 1U/kg during acute myocardial ischemia, make the acute myocardial ischemia model behind the 30min), when adding pill for promoting coronary circulation behind the ischemia (injection ADH5min clock after administration), the spectral change of the HRV of (administration behind the injection ADH5min clock) when adding oral cavity disintegration tablet of the present invention behind the ischemia, wherein acute myocardial ischemia is in 1min, 5min writes down spectral change, the administration group behind the ischemia in administration at once, 5min record spectral change after the administration.The pill for promoting coronary circulation dosage is 0.5 ball/rabbit, and the pit of the stomach disintegrating tablet dosage of living is a 0.5/rabbit.The results are shown in Table 8.
The variation of HRV under table 8 different situations
| Group | TV(ms) | LF(ms) | HF(ms) |
| Add oral cavity disintegration tablet group of the present invention after adding pill group ischemia behind the normal group acute myocardial ischemia group ischemia | 2.56±0.29 8.45±1.15 21.05±2.40 △△ 32.10±2.65 △△* | 0.49±0.08 3.08±0.45 8.20±1.55 △△ 13.70±1.62 △△* | 0.55±0.05 2.89±0.54 1.23±0.15 △△ 0.85±0.06 △△* |
Compare with the acute myocardial ischemia group:
△ △P＜0.01; With take the pill for promoting coronary circulation group relatively: the above result of the test in * P＜0.05 shows: the heart preparation of living behind the acute myocardial ischemia, total variability obviously increases, LF increases, HF diminishes, and LF/HF also increases, and shows that heart preparation alive can adjust autonomic nervous function, especially adjust sympathetic nerve and vagal excitation proper proportion, help cardiac function and recover, improve myocardial ischemia, oral cavity disintegration tablet effect wherein of the present invention is significantly better than pill for promoting coronary circulation.
2. to the protective effect of Canis familiaris L. expeirmental myocardial ischemia
Get totally 9 of Beagle Canis familiaris L.s, body weight 7.5-10kg, be divided into matched group, the pill for promoting coronary circulation group, oral cavity disintegration tablet group of the present invention, difference 1/d of oral pill for promoting coronary circulation and 1/d of oral cavity disintegration tablet of the present invention before the operation of administration group, be total to 3d, with pentobarbital sodium 25mg/kg intravenous anesthesia, tracheal intubation connects artificial respirator positive pressure respiration in addition, and the 5th rib is opened breast from the left side, cut off pericardium, expose heart, the pericardial incision edge is sewn in thoracic wall, divide the second stage of ligation at ramus descendens anterior arteriae coronariae sinistrae, and slow iv lignocaine 8mg/kg is in case the ventricular fibrillation that may cause before the ligation is sewed up pericardium and thoracic wall subsequently.24h behind the heart infarction, Canis familiaris L. is put to death after pentobarbital sodium anesthesia, take out heart rapidly, excision trunk and fatty tissue, check the position of anterior descending branch ligation point, claim heavy whole-heartedly, excise right ventricle and left atrium then, stay interventricular septum and left atrium, claim to such an extent that left ventricle is heavy, from the apex of the heart and beginning and anterior descending branch vertical direction left ventricle is cut into the thick flesh sheet of 2-3mm, be dipped in dyeing 30min in the nitro tetrazolium blue solution (NBT), cut ischemic region cardiac muscular tissue and weigh, the calculating myocardium infarction size, that is: heart infarction scope=ischemic region weight/left ventricle is heavy by * 100%, the results are shown in Table 9.
The influence of table 9 pair Cor Canitis chamber infarction size
| Group | Heavy (g) whole-heartedly | Chamber, a left side heavy (g) | Ischemic region heavy (g) | Heart infarction scope (%) |
| Matched group pill for promoting coronary circulation group oral cavity disintegration tablet group of the present invention | 65.50±8.51 66.52±8.75 67.82±8.83 | 42.90±5.02 46.31±4.24 48.86±4.57 | 9.49±0.82 4.47±0.59 2.93±0.45 | 22.12±1.79 9.65±1.58** 6.00±1.10** △ |
Compare with matched group: * * P＜0.01; Compare with the pill for promoting coronary circulation group:
△P＜0.05
Above experimental result shows that heart preparation alive can obviously make Cor Canitis stalk scope dwindle, and wherein the effect of oral cavity disintegration tablet of the present invention is more remarkable.
3. to the irritation test of gastric mucosa
Select 40 of healthy mices, fasting 24h freely drinks water, and is divided into 4 groups at random by the equilibrium of body weight sex; Gastric infusion, for being equivalent to pill 100mg/kg, small dose group is equivalent to pill 50mg/kg to dosage by the heavy dose of group of crude drug amount conversion; Behind the administration 5h, take off neck and put to death, open the abdominal cavity, free full stomach is put in 5% formaldehyde and is fixed, and along greater gastric curvature stomach is cut off, and observes the length of gastric bleeding damage down in stereoscopic microscope; As the index of estimating ulcer level, the results are shown in Table 10 with all damaged length sums of every mice stomach.
The irritation test of table 10 pair gastric mucosa
| Group | Gastric bleeding (mm) |
| Pill for promoting coronary circulation group (heavy dose of group) pill for promoting coronary circulation group (small dose group) oral cavity disintegration tablet group of the present invention (heavy dose of group) oral cavity disintegration tablet group of the present invention (small dose group) | 1.52±0.45 0.95±0.28 0.52±0.25 0.37±0.19 |
Compare with matched group: * * P＜0.01; Compare with the pill for promoting coronary circulation group:
△P＜0.05
The result shows, compares with pill for promoting coronary circulation, and oral cavity disintegration tablet of the present invention significantly reduces the zest of gastric mucosa.
Above pharmacological evaluation proves, with heart activating oral disintergration tablet coronary heart disease, angina pectoris are had better therapeutic effect, and zest is littler.
Seven, preparation embodiment
Embodiment 1
(1) the crude drug weight proportion is: Ganoderma 200g, Moschus 5g, Fel Ursi 5g, Flos Carthami 100g, Calculus Bovis 5g, Margarita 5g, Radix Ginseng 200g, Venenum Bufonis 100g, Radix Aconiti Lateralis Preparata 100g, Borneolum Syntheticum 5g;
(2) Ganoderma, Flos Carthami are decocted with water secondary, 1.5 hours for the first time, 1 hour for the second time, decoction liquor filtered, and merged, concentrate and vacuum drying, get Ganoderma, Flos Carthami extract, 85% alcohol reflux of Radix Aconiti Lateralis Preparata usefulness pH2-3 2 times, merge extractive liquid,, decompression recycling ethanol also concentrates, and gets Radix Aconiti Lateralis Preparata extract; Radix Ginseng merges backflow with 50% alcohol reflux 3 times, filters, and filtrate concentrates and is dry, Radix Ginseng extract; Merge Ganoderma, Flos Carthami extract, Radix Aconiti Lateralis Preparata extract, Radix Ginseng extract and Calculus Bovis, Margarita are pulverized, and get drug powder;
(3) get Moschus, Venenum Bufonis and leach with 10 times of amount 75% ethanol, leachate filters, and decompression recycling ethanol also concentrates; Fel Ursi, Borneolum Syntheticum dissolve with small amount of ethanol; The ethanol liquid of Fel Ursi, Borneolum Syntheticum is joined in above-mentioned Moschus, the Venenum Bufonis extracting solution; Slowly join in the saturated aqueous solution of 10 times of amount beta-schardinger dextrin-s, 50 ℃ were stirred 3 hours, continued under the room temperature to stir 2 hours, and cold preservation is spent the night, and filters, and cold drying obtains clathrate;
(4) preparation prescription of the present invention is: drug powder 90g, clathrate 300g, microcrystalline Cellulose 380g, crosslinked carboxymethylstach sodium 140g, aspartame 10g, magnesium stearate 10g;
(5) said medicine extract fine powder, clathrate are mixed with pharmaceutic adjuvant, system granule, tabletting, check, packing obtain 10000 of oral cavity disintegration tablets of the present invention.
Embodiment 2
(1) the crude drug weight proportion is: Ganoderma 200g, Moschus 5g, Fel Ursi 5g, Flos Carthami 100g, Calculus Bovis 5g, Margarita 5g, Radix Ginseng 200g, Venenum Bufonis 100g, Radix Aconiti Lateralis Preparata 100g, Borneolum Syntheticum 5g;
(2) Ganoderma, Flos Carthami are decocted with water secondary, 1.5 hours for the first time, 1 hour for the second time, decoction liquor filtered, and merged, concentrate and vacuum drying, get Ganoderma, Flos Carthami extract, 80% alcohol reflux of Radix Aconiti Lateralis Preparata usefulness pH2-3 2 times, merge extractive liquid,, decompression recycling ethanol also concentrates, and gets Radix Aconiti Lateralis Preparata extract; Radix Ginseng merges backflow with 40% alcohol reflux 3 times, filters, and filtrate concentrates and is dry, Radix Ginseng extract; Merge Ganoderma, Flos Carthami extract, Radix Aconiti Lateralis Preparata extract, Radix Ginseng extract and Margarita are pulverized, and get drug powder;
(3) get Moschus, Venenum Bufonis and leach with 8 times of amount 70% ethanol, leachate filters, and decompression recycling ethanol also concentrates; Fel Ursi, Borneolum Syntheticum dissolve with small amount of ethanol; The ethanol liquid of Fel Ursi, Borneolum Syntheticum is joined in above-mentioned Moschus, the Venenum Bufonis extracting solution; Slowly join in the saturated aqueous solution of 8 times of amount beta-schardinger dextrin-s, 50 ℃ were stirred 2 hours, continued under the room temperature to stir 2 hours, and cold preservation is spent the night, and filters, and cold drying obtains clathrate;
(4) preparation prescription of the present invention is: drug powder 80g, clathrate 250g, microcrystalline Cellulose 350g, crosslinked carboxymethylstach sodium 80g, crospolyvinylpyrrolidone 40g, aspartame 15g, magnesium stearate 9g;
(5) said medicine extract fine powder, clathrate are mixed with pharmaceutic adjuvant, system granule, tabletting, check, packing obtain 10000 of oral cavity disintegration tablets of the present invention.
Embodiment 3
(1) the crude drug weight proportion is: Ganoderma 100g, Moschus 3g, Fel Ursi 3g, Flos Carthami 50g, Calculus Bovis 3g, Margarita 3g, Radix Ginseng 100g, Venenum Bufonis 50g, Radix Aconiti Lateralis Preparata 50g, Borneolum Syntheticum 3g;
(2) Ganoderma, Flos Carthami are decocted with water secondary, 1.5 hours for the first time, 1 hour for the second time, decoction liquor filtered, and merged, concentrate and vacuum drying, get Ganoderma, Flos Carthami extract, 90% alcohol reflux of Radix Aconiti Lateralis Preparata usefulness pH2-3 2 times, merge extractive liquid,, decompression recycling ethanol also concentrates, and gets Radix Aconiti Lateralis Preparata extract; Radix Ginseng merges backflow with 60% alcohol reflux 3 times, filters, and filtrate concentrates and is dry, Radix Ginseng extract; Merge Ganoderma, Flos Carthami extract, Radix Aconiti Lateralis Preparata extract, Radix Ginseng extract and Margarita are pulverized, and get drug powder;
(3) get Moschus, Venenum Bufonis and leach with 12 times of amount 80% ethanol, leachate filters, and decompression recycling ethanol also concentrates; Fel Ursi, Borneolum Syntheticum dissolve with small amount of ethanol; The ethanol liquid of Fel Ursi, Borneolum Syntheticum is joined in above-mentioned Moschus, the Venenum Bufonis extracting solution; Slowly join in the saturated aqueous solution of 15 times of amount beta-schardinger dextrin-s, 50 ℃ were stirred 4 hours, continued under the room temperature to stir 2 hours, and cold preservation is spent the night, and filters, and cold drying obtains clathrate;
(4) preparation prescription of the present invention is: drug powder 60g, and clathrate 270g, microcrystalline Cellulose 330g, cross-linking sodium carboxymethyl cellulose 120g,, aspartame 12g, micropowder silica gel 8g;
(5) said medicine extract fine powder, clathrate are mixed with pharmaceutic adjuvant, system granule, tabletting, check, packing obtain 10000 of oral cavity disintegration tablets of the present invention.
Embodiment 4
(1) the crude drug weight proportion is: Ganoderma 300g, Moschus 8g, Fel Ursi 8g, Flos Carthami 200g, Calculus Bovis 8g, Margarita 8g, Radix Ginseng 300g, Venenum Bufonis 200g, Radix Aconiti Lateralis Preparata 200g, Borneolum Syntheticum 8g;
(2) Ganoderma, Flos Carthami are decocted with water secondary, 1.5 hours for the first time, 1 hour for the second time, decoction liquor filtered, and merged, concentrate and vacuum drying, get Ganoderma, Flos Carthami extract, 80% alcohol reflux of Radix Aconiti Lateralis Preparata usefulness pH2-3 2 times, merge extractive liquid,, decompression recycling ethanol also concentrates, and gets Radix Aconiti Lateralis Preparata extract; Radix Ginseng merges backflow with 40% alcohol reflux 3 times, filters, and filtrate concentrates and is dry, Radix Ginseng extract; Merge Ganoderma, Flos Carthami extract, Radix Aconiti Lateralis Preparata extract, Radix Ginseng extract and Margarita are pulverized, and get drug powder;
(3) get Moschus, Venenum Bufonis and leach with 8 times of amount 75% ethanol, leachate filters, and decompression recycling ethanol also concentrates; Fel Ursi, Borneolum Syntheticum dissolve with small amount of ethanol; The ethanol liquid of Fel Ursi, Borneolum Syntheticum is joined in above-mentioned Moschus, the Venenum Bufonis extracting solution; Slowly join in the saturated aqueous solution of 10 times of amount beta-schardinger dextrin-s, 50 ℃ were stirred 3 hours, continued under the room temperature to stir 2 hours, and cold preservation is spent the night, and filters, and cold drying obtains clathrate;
(4) preparation prescription of the present invention is: drug powder 150g, clathrate 400g, microcrystalline Cellulose 495g, crosslinked carboxymethylstach sodium 120g, cross-linking sodium carboxymethyl cellulose 80g, steviosin 25g, magnesium stearate 30g;
(5) said medicine extract fine powder, clathrate are mixed with pharmaceutic adjuvant, system granule, tabletting, check, packing obtain 10000 of oral cavity disintegration tablets of the present invention.
Embodiment 5
(1) the crude drug weight proportion is: Ganoderma 200g, Moschus 5g, Fel Ursi 5g, Flos Carthami 100g, Calculus Bovis 5g, Margarita 5g, Radix Ginseng 200g, Venenum Bufonis 100g, Radix Aconiti Lateralis Preparata 100g, Borneolum Syntheticum 5g;
(2) Ganoderma, Flos Carthami are decocted with water secondary, 1.5 hours for the first time, 1 hour for the second time, decoction liquor filtered, and merged, concentrate and vacuum drying, get Ganoderma, Flos Carthami extract, 85% alcohol reflux of Radix Aconiti Lateralis Preparata usefulness pH2-3 2 times, merge extractive liquid,, decompression recycling ethanol also concentrates, and gets Radix Aconiti Lateralis Preparata extract; Radix Ginseng merges backflow with 50% alcohol reflux 3 times, filters, and filtrate concentrates and is dry, Radix Ginseng extract; Merge Ganoderma, Flos Carthami extract, Radix Aconiti Lateralis Preparata extract, Radix Ginseng extract and Margarita are pulverized, and get drug powder;
(3) get Moschus, Venenum Bufonis and leach with 10 times of amount 75% ethanol, leachate filters, and decompression recycling ethanol also concentrates; Fel Ursi, Borneolum Syntheticum dissolve with small amount of ethanol; The ethanol liquid of Fel Ursi, Borneolum Syntheticum is joined in above-mentioned Moschus, the Venenum Bufonis extracting solution; Slowly join in the saturated aqueous solution of 12 times of amount beta-schardinger dextrin-s, 50 ℃ were stirred 2 hours, continued under the room temperature to stir 2 hours, and cold preservation is spent the night, and filters, and cold drying obtains clathrate;
(4) preparation prescription of the present invention is: drug powder 100g, clathrate 350g, microcrystalline Cellulose 463g, crospolyvinylpyrrolidone 100g, low-substituted hydroxypropyl cellulose 65g, sucralose 11g, micropowder silica gel 11g;
(5) said medicine extract fine powder, clathrate are mixed with pharmaceutic adjuvant, system granule, tabletting, check, packing obtain 10000 of oral cavity disintegration tablets of the present invention.
Embodiment 6
(1) the crude drug weight proportion is: Ganoderma 200g, Moschus 5g, Fel Ursi 5g, Flos Carthami 100g, Calculus Bovis 5g, Margarita 5g, Radix Ginseng 200g, Venenum Bufonis 100g, Radix Aconiti Lateralis Preparata 100g, Borneolum Syntheticum 5g;
(2) Ganoderma, Flos Carthami are decocted with water secondary, 1.5 hours for the first time, 1 hour for the second time, decoction liquor filtered, and merged, concentrate and vacuum drying, get Ganoderma, Flos Carthami extract, 85% alcohol reflux of Radix Aconiti Lateralis Preparata usefulness pH2-3 2 times, merge extractive liquid,, decompression recycling ethanol also concentrates, and gets Radix Aconiti Lateralis Preparata extract; Radix Ginseng merges backflow with 50% alcohol reflux 3 times, filters, and filtrate concentrates and is dry, Radix Ginseng extract; Merge Ganoderma, Flos Carthami extract, Radix Aconiti Lateralis Preparata extract, Radix Ginseng extract and Margarita are pulverized, and get drug powder;
(3) get Moschus, Venenum Bufonis and leach with 10 times of amount 75% ethanol, leachate filters, and decompression recycling ethanol also concentrates; Fel Ursi, Borneolum Syntheticum dissolve with small amount of ethanol; The ethanol liquid of Fel Ursi, Borneolum Syntheticum is joined in above-mentioned Moschus, the Venenum Bufonis extracting solution; Slowly join in the saturated aqueous solution of 12 times of amount beta-schardinger dextrin-s, 50 ℃ were stirred 2 hours, continued under the room temperature to stir 2 hours, and cold preservation is spent the night, and filters, and cold drying obtains clathrate;
(4) preparation prescription of the present invention is: drug powder 90g, clathrate 340g, microcrystalline Cellulose 470g, low-substituted hydroxypropyl cellulose 165g, aspartame 20g, sodium lauryl sulphate 15g;
(5) said medicine extract fine powder, clathrate are mixed with pharmaceutic adjuvant, system granule, tabletting, check, packing obtain 10000 of oral cavity disintegration tablets of the present invention.
Claims (3)
1. heart activating oral disintergration tablet, it is characterized in that it is by Ganoderma, Flos Carthami extract, Radix Aconiti Lateralis Preparata extract, Radix Ginseng extract, drug powder 6-15 part that Calculus Bovis, crushing pearl obtain and Moschus, Venenum Bufonis extract, Fel Ursi, the effective ingredient that Benexate Hydrochloride 27-40 part of Borneolum Syntheticum is formed accounts for 40%-44%, and pharmaceutic adjuvant is that 56%-60% is prepared from; Wherein filler is 38%-43% in the pharmaceutic adjuvant, and disintegrating agent is 14%-16%, and correctives is 1%-2%, and lubricant is 1%-3%.
2. according to a kind of heart activating oral disintergration tablet of claim 1, filler is a microcrystalline Cellulose, and disintegrating agent is one or both the mixture in low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, crospolyvinylpyrrolidone, the crosslinked carboxymethyl fecula sodium.
3. the preparation method of a heart activating oral disintergration tablet is characterized by:
(1) the crude drug weight proportion is: Ganoderma 100-300 part, Moschus 3-8 part, Fel Ursi 3-8 part, Flos Carthami 50-200 part, Calculus Bovis 3-8 part, Margarita 3-8 part, Radix Ginseng 100-300 part, Venenum Bufonis 50-200 part, Radix Aconiti Lateralis Preparata 50-200 part, Borneolum Syntheticum 3-8 part;
(2) Ganoderma, Flos Carthami are decocted with water secondary, 1.5 hours for the first time, 1 hour for the second time, decoction liquor filtered, and merged, concentrate and vacuum drying, get Ganoderma, Flos Carthami extract, the 80-90% alcohol reflux of Radix Aconiti Lateralis Preparata usefulness pH2-3 2 times, merge extractive liquid,, decompression recycling ethanol also concentrates, and gets Radix Aconiti Lateralis Preparata extract; Radix Ginseng 40-60% alcohol reflux 3 times, the merging backflow filters, and filtrate concentrates and drying, gets Radix Ginseng extract; Merge Ganoderma, Flos Carthami extract, Radix Aconiti Lateralis Preparata extract, Radix Ginseng extract and Calculus Bovis, Margarita are pulverized, and get drug powder.
(3) get Moschus, Venenum Bufonis and doubly measure 70-80% ethanol with 8-12 and leach, leachate filters, and decompression recycling ethanol also concentrates; Fel Ursi, Borneolum Syntheticum dissolve with small amount of ethanol; The ethanol liquid of Fel Ursi, Borneolum Syntheticum is joined in above-mentioned Moschus, the Venenum Bufonis extracting solution; Slowly join 8-15 and doubly measure in the saturated aqueous solution of beta-schardinger dextrin-, 50 ℃ were stirred 2-4 hour, continued under the room temperature to stir 2 hours, and cold preservation is spent the night, and filters, and cold drying obtains clathrate;
(4) said medicine powder, clathrate and pharmaceutic adjuvant are mixed in proportion, granulation, drying, granulate, tabletting, check, packing obtain oral cavity disintegration tablet.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2005100870212A CN1899397A (en) | 2005-07-22 | 2005-07-22 | Heart activating oral disintergration tablet and its preparing method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2005100870212A CN1899397A (en) | 2005-07-22 | 2005-07-22 | Heart activating oral disintergration tablet and its preparing method |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108057066A (en) * | 2018-02-11 | 2018-05-22 | 广州白云山医药集团股份有限公司白云山制药总厂 | A kind of pharmaceutical composition for preventing unstable angina pectoris |
| CN109061010A (en) * | 2018-10-18 | 2018-12-21 | 广州悦康生物制药有限公司 | The detection method of content of bornyl alcohol in pill for promoting coronary circulation is concentrated |
| WO2023024332A1 (en) * | 2021-08-27 | 2023-03-02 | 广州白云山医药集团股份有限公司白云山制药总厂 | Application of composition in preparation of drug for preventing and treating stroke |
-
2005
- 2005-07-22 CN CNA2005100870212A patent/CN1899397A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108057066A (en) * | 2018-02-11 | 2018-05-22 | 广州白云山医药集团股份有限公司白云山制药总厂 | A kind of pharmaceutical composition for preventing unstable angina pectoris |
| CN108057066B (en) * | 2018-02-11 | 2021-02-26 | 广州白云山医药集团股份有限公司白云山制药总厂 | Pharmaceutical composition for preventing and treating unstable angina |
| CN109061010A (en) * | 2018-10-18 | 2018-12-21 | 广州悦康生物制药有限公司 | The detection method of content of bornyl alcohol in pill for promoting coronary circulation is concentrated |
| WO2023024332A1 (en) * | 2021-08-27 | 2023-03-02 | 广州白云山医药集团股份有限公司白云山制药总厂 | Application of composition in preparation of drug for preventing and treating stroke |
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