CN1748776A - Anti-virus lozenge or anti-virus chewing tablet and its preparing method - Google Patents
Anti-virus lozenge or anti-virus chewing tablet and its preparing method Download PDFInfo
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- CN1748776A CN1748776A CN 200410040669 CN200410040669A CN1748776A CN 1748776 A CN1748776 A CN 1748776A CN 200410040669 CN200410040669 CN 200410040669 CN 200410040669 A CN200410040669 A CN 200410040669A CN 1748776 A CN1748776 A CN 1748776A
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Abstract
The antiviral lozenge or antiviral chewing tablet is prepared with nine kinds of Chinese medicinal materials, including isatis root, gypsum, reed rhizome, rehmannia root, curcuma root, etc. The preparation process includes the following steps: decocting, collecting volatile oil and concentrating; adding alcohol, filtering, concentrating to obtain extractum; mixing the extractum, excipient, corrective and coated volatile oil, pelletizing, drying and tabletting to form the antiviral lozenge or antiviral chewing tablet. The content of forsythin as the effective component is measured through liquid phase chromatographic method. The antiviral lozenge or antiviral chewing tablet is dissolved slowly in oral cavity for mucous membrane to absorb and to generate antiviral effect, and is especially suitable for those people with dysphagia and children.
Description
Technical field the present invention is antivirus buccal tablet or antivirus chewing tablet and preparation method thereof.Belong to pharmaceutical sanitary field.
Background technology anti-viral pharmaceutical compositions of the present invention is based on " eliminating pestilence and relieving toxicity drink " in " Baihu Tang " in the Zhang Zhongjing " typhoid fever note " and surplus Shi Yu " epidemic disease is examined one and got ", and plus-minus forms.The pure compound Chinese medicinal preparation that adopts modern science and technology to develop, its function cure mainly into: clearing heat and expelling damp, removing pathogenic heat from blood and toxic substance from the body is used for anemopyretic cold, virus infectious diseases such as epidemic febrile disease heating and upper respiratory tract infection, influenza, parotid gland class.
The maximum characteristics of epidemic virus flu are cause of disease complexity, infectiousness is strong and easy repeated infection.All can fall ill throughout the year.Sickness rate is different with changes of seasons, and general the end of spring and the beginning of summer is season occurred frequently.The old children irrespective of sex of Susceptible population.Because the infectious rate of epidemic virus flu is high, therefore treatment is very important with prevention.So on China's Chinese medicine history, have tens of kinds of anti-viral pharmaceutical compositions prescription to use clinically and carrier format that multiple medications arranged in market sale.Antivirus oral liquid, granule, sheet extensive use with Radix Isatidis, Gypsum Fibrosum, Rhizoma Phragmitis, Radix Rehmanniae, Radix Curcumae, the Rhizoma Anemarrhenae, Rhizoma Acori Graminei, Herba Pogostemonis, Fructus Forsythiae nine flavor Chinese medicines compositions.But each flavour of a drug combination matching has nothing in common with each other,
Oral buccal tablet or chewable tablet are compared with oral liquid has in the oral cavity slowly dissolving, produces the preventive and therapeutic effect except that absorbing by mucosa, contains the saliva of medicine stripping composition, directly enters gastric and absorbs produce effects by swallowing.Buccal tablet is applicable to senile disease patient and weakling's medication of dysphagia, especially is subjected to liking of child; Buccal tablet is compared with oral liquid, mucosa absorbance height, and the good biological that is beneficial to very much the propagation source that cuts off virus is learned the pharmaceutics feature, also is convenient to the characteristics of preserving, transporting.Compare advantage with taking convenience with granule.In the high-incidence season of epidemic virus flu, buccal tablet can be carried, and taking convenience is optimal selection as prophylactic.
Summary of the invention the object of the invention first purpose is to excavate and raising motherland medicine legacy, determine each flavour of a drug combination matching, adopt modern preparation technique, for the senile disease patient of dysphagia and weakling provide a kind of pharmaceutical carrier form that can buccal is swallowed after can chewing again in mouth.
Another purpose of the present invention is to collect volatile oil, and it is carried out the enclose sealing with inclusion technique, with better preservation effective ingredient, improves curative effect.
Contain tablet form and promptly be applicable to taking of various Susceptible population, more be applicable to the senile disease patient and the weakling of dysphagia, as prophylactic, a kind of especially ideal dosage form selection, the child particularly likes.Among the preparation technology, volatile ingredient has been adopted advanced betacyclodextrin inclusion technique,, thereby guaranteed clinical efficacy with better preservation effective ingredient.For satisfying diabetes patient's medication needs, the correctives of employing is non-sugared type.By meticulous screening adjuvant, the mouthfeel of antivirus buccal tablet is pleasant, promptly has the sweetness of Radix Isatidis, Rhizoma Phragmitis and Fructus Forsythiae to omit the hot fragrance that bitterness has Herba Pogostemonis, Rhizoma Acori Graminei again.Buccal tablet compare with oral liquid have storage, the more convenient characteristics of transportation.Compare advantage with taking convenience with granule.In the high-incidence season of epidemic virus flu, buccal tablet can be carried, and taking convenience is optimal selection as prophylactic.
First purpose of the present invention realizes by following steps.
With the Radix Isatidis clearing away heat,cooling blood and removing toxin, Chinese medicine is thought kind pestilence calentura, laryngopharynx swelling and pain, the scarlet fever controlled of this product; Modern study confirms that Radix Isatidis has the effect of antiviral bacteriostatic, and energy enhancing body defensive enginery; The Gypsum Fibrosum resolving heat and reducing pathogenic fire; Radix Rehmanniae nourishing YIN and clearing away heat; The Fructus Forsythiae heat-clearing and toxic substances removing is controlled the exterior and the interior heating; Rhizoma Anemarrhenae nourishing YIN to lower pathogenic fire; Stomach-fire falls in Rhizoma Phragmitis, clearing away lung-heat and emesis.This product is at upper respiratory tract infection, is outstanding symptom prescription with heating, and that we get is sweet, bitter, hot, constipation due to pathogenic cold closes, resolving heat and reducing pathogenic fire and non-impairment of YIN.Tool antiviral, antibiotic, antiinflammatory antipyretic effect.
The combination of Radix Isatidis, Gypsum Fibrosum, Rhizoma Phragmitis, Radix Rehmanniae, Radix Curcumae, the Rhizoma Anemarrhenae, Rhizoma Acori Graminei, Herba Pogostemonis, each flavour of a drug of Fructus Forsythiae is than being Radix Isatidis 600-700g, Gypsum Fibrosum 250-300g, Rhizoma Phragmitis 275-325g, Radix Rehmanniae 140-180g, Radix Curcumae 100-150g, Rhizoma Anemarrhenae 100-150g, Rhizoma Acori Graminei 100-150g, Herba Pogostemonis 120-160g, Fructus Forsythiae 200-260g.
Preferable combination is than Radix Isatidis 640-645g, Gypsum Fibrosum 284-287g, Rhizoma Phragmitis 300-305g, Radix Rehmanniae 158-162g, Radix Curcumae 124-126g, Rhizoma Anemarrhenae 124-126g, Rhizoma Acori Graminei 124-126g, Herba Pogostemonis 140-145g, Fructus Forsythiae 230-234g between each flavour of a drug.
Best of breed is than Radix Isatidis 642.9g, Gypsum Fibrosum 285.7g, Rhizoma Phragmitis 303.6g, Radix Rehmanniae 160.7g, Radix Curcumae 125g, Rhizoma Anemarrhenae 125g, Rhizoma Acori Graminei 125g, Herba Pogostemonis 142.9g, Fructus Forsythiae 232.1g between each flavour of a drug.
With above nine herbal medicines, decoct with water, concentrate; Add ethanol, leave standstill, filter, behind filtrate recycling ethanol, concentrate and obtain extractum; Concentrate the extractum that obtains and be equipped with an amount of suitable excipient and correctives, granulate.Drying, compacting promptly gets antivirus buccal tablet or antivirus chewing tablet in flakes.
With above nine herbal medicines, decoct with water secondary, add 6-10 for the first time and doubly measure, decocted 0.5-2.5 hour; For the second time add 4-8 and doubly measure, decocted 0.5-2.5 hour, collecting decoction, medicinal liquid concentrate after crossing the 60-200 mesh sieve; Add ethanol and make precipitation, leave standstill, filter, behind filtrate recycling ethanol, be concentrated into the extractum that relative density is 1.00-1.300.Granulate with an amount of excipient and correctives.Drying, granulate.Tabletting promptly gets antivirus buccal tablet or antivirus chewing tablet.
Excipient is starch, soluble starch, lactose, mannitol, maltodextrin, is the best with soluble starch and lactose.
Correctives is aspartame, glucide, steviol glycosides, citric acid, essence, Herba Menthae and Oleum menthae, is best with the aspartame.
Antivirus buccal tablet for preparing or antivirus chewing tablet adopt liquid chromatography for measuring index composition or active ingredient lotus to stick up the content of glycosides.
Its described liquid chromatography is:
A: the test of chromatographic condition and system suitability is for being filler with 8 carbon alkyl to the alkyl linked silica gel of 18 carbon; Acetonitrile-biphosphate receives (phosphoric acid transfer pH to 2.5-4.0)-and methanol is mobile phase; The detection wavelength is 220-240nm.Number of theoretical plate calculates by the phillyrin peak should be not less than 800.
B: need testing solution preparation: get this product and add methanol extraction, precision is measured extracting solution, is added on the neutral alumina post, with ethanol elution, collects eluent, evaporate to dryness with dissolve with methanol, and is transferred in the measuring bottle, is diluted to scale, shakes up, filter, it is centrifugal to get subsequent filtrate, gets supernatant, promptly.
C: the reference substance solution preparation: it is an amount of to get phillyrin, adds methanol and is diluted to, in contrast product solution.
D: algoscopy: accurate respectively reference substance solution and the need testing solution drawn, inject high performance liquid chromatograph, measure and calculate promptly.
Every of this product contains Fructus Forsythiae with phillyrin (C
29H
36O
15) meter, must not be less than 0.015mg.
Another purpose of the present invention realizes by following steps.
With Radix Isatidis, Gypsum Fibrosum, Rhizoma Phragmitis, Radix Rehmanniae, Radix Curcumae, the Rhizoma Anemarrhenae, Rhizoma Acori Graminei, Herba Pogostemonis, the antiviral flavour of a drug combined preparation antivirus buccal tablet of Fructus Forsythiae composition or the preparation technology of antivirus chewing tablet medicine,
A: collect volatile oil when decocting with water, collected volatile oil comprises volatile oil emulsion, and volatile oil emulsion redistillation is got volatile oil.
B: volatile oil carries out enclose in right amount with the hole excipient.Enclose is a beta-schardinger dextrin-with porous crack excipient, maltodextrin, and porous crack starch or macrovoid starch etc. are best with the beta-schardinger dextrin-.When carrying out enclose with ultrasonic bag be the best.
In the technical process that adopts above-mentioned prepared antivirus buccal tablet or antivirus chewing tablet, adopt the content that liquid chromatography for measuring index composition or active ingredient lotus stick up glycosides to carry out the technology detection.
The antivirus buccal tablet or the antivirus chewing tablet that adopt above-mentioned prepared to obtain adopt liquid chromatography for measuring index composition or active ingredient lotus to stick up the content of glycosides.
Described liquid chromatography is:
A: the test of chromatographic condition and system suitability is for being filler with 8 carbon alkyl to the alkyl linked silica gel of 18 carbon; Acetonitrile-biphosphate receives (phosphoric acid transfer pH to 2.5-4.0)-and methanol is mobile phase; The detection wavelength is 220-240nm.Number of theoretical plate calculates by the phillyrin peak should be not less than 800.
B: need testing solution preparation: get this product and add methanol extraction, precision is measured extracting solution, is added on the neutral alumina post, with ethanol elution, collects eluent, evaporate to dryness with dissolve with methanol, and is transferred in the measuring bottle, is diluted to scale, shakes up, filter, it is centrifugal to get subsequent filtrate, gets supernatant, promptly.
C: the reference substance solution preparation: it is an amount of to get phillyrin, adds methanol and is diluted to, in contrast product solution.
D: algoscopy: accurate respectively reference substance solution and the need testing solution drawn, inject high performance liquid chromatograph, measure and calculate promptly.
Every of this product contains Fructus Forsythiae with phillyrin (C
29H
36O
15) meter, must not be less than 0.03mg.
Further elaborate the present invention below.
The isolation and purification technical study:
Because the concentration of alcohol behind the preceding medicine liquid volume of precipitate with ethanol, adding concentration of ethanol, the precipitate with ethanol in the medicinal liquid has considerable influence to the precipitate with ethanol effect, therefore, select above-mentioned three to be the investigation factor, respectively get 3 levels and carry out orthogonal test, and be evaluation index with the content of phillyrin in the extractum weight that is concentrated into prescribed volume behind the precipitate with ethanol and the extractum, screening optimum process condition (the content weight coefficient that is concentrated into phillyrin in prescribed volume extractum weight and the extractum behind the precipitate with ethanol is respectively 0.4,0.6).See Fig. 1.
Each experiment feeds intake by 0.1 times of recipe quantity, and medicinal liquid all is concentrated into 60ml behind the precipitate with ethanol, claims to decide weight, record; Measure the content of phillyrin in every milliliter of extractum; The extractum weight that medicinal liquid is concentrated into 60ml after testing precipitate with ethanol as can be known is all less than 100g, for ease of date processing, is evaluation index with " 100 deduct precipitate with ethanol then be concentrated into prescribed volume extractum weight " gained data in the orthogonal test table.Result of the test is seen Fig. 2.
As seen, each factor affecting size order is from Fig. 1, Fig. 2, Fig. 3: A＞C＞B＞D, and wherein A has significance, and the precipitate with ethanol optimised process is A
1B
2C
2But consider that the big production of factory need save time and the energy, reduce cost, and A
2B
2C
3Comprehensive grading is the highest, so select A
2B
2C
3Be this product alcohol precipitation process condition.Promptly 0.1 times of recipe quantity medicinal liquid is concentrated into 125ml, adds 90% ethanol 250ml and makes medicinal liquid contain alcohol amount to reach 60%.
Enclose volatile oil technical study:
Volatile oil emulsion oil, water are not easily separated, thereby it is standby that volatile oil emulsion redistillation is got volatile oil.
The contained volatile oil of we is more, and is volatile and influence the quality of the pharmaceutical preparations if directly spray into tabletting in the granule, thus definite be beta-schardinger dextrin-(promptly times he-cyclodextrin) with porous crack excipient, maltodextrin, porous crack starch or macrovoid starch etc. carries out enclose.
Beta-schardinger dextrin-CD carries out enclose (or parcel).Volatile oil behind parcel, not only stability strengthens, and zest, bad smell reduce, and simultaneously, makes volatile oil liquid become solid powdering again, is convenient to preparation.
Concrete grammar is: take by weighing predetermined amount of beta-cyclodextrin, adding quantitative distilled water shakes up, mix with a certain amount of volatile oil ethanol solution (50%V/V), shake well behind 40 ℃ of ultrasonic certain hours, is put the refrigerator and cooled Tibetan and is spent the night, sucking filtration, clathrate is crossed 80 mesh sieves in 40 ℃ of dryings 4 hours, promptly gets off-white powder shape volatile oil beta cyclodextrin inclusion complex.
Clathrate recovery rate, oil recovery rate are measured: the accurate title of dry clathrate of gained is fixed, put in the round-bottomed flask that zeolite is housed, adding distil water 100ml, connect volatile oil extractor, by " pertinent regulations are carried out under an appendix determination of volatile oil of Chinese pharmacopoeia version in 2000 item, when heated and boiled no longer increases to oil mass, stop heating, place and read the volatilization oil mass in 30 minutes, be converted to the actual oil content of clathrate, calculate clathrate recovery rate, oil recovery rate.
Because beta-schardinger dextrin-consumption, amount of water and ultrasonic time have considerable influence to inclusion essential oil, therefore, select above-mentioned three to be the investigation factor, respectively get 3 levels and carry out orthogonal test such as Fig. 4, and be evaluation index with the response rate of clathrate recovery rate, clathrate medium oil, screening optimum process condition (clathrate recovery rate and clathrate oil recovery rate weight coefficient are respectively 0.4 and 0.6), concrete outcome is seen Fig. 5.
As seen, each factor affecting size order is from Fig. 4, Fig. 5, Fig. 6: B＞A＞C＞D, wherein B, A have significance, so determine that optimised process is A
2B
2C
3, promptly every 1ml volatile oil 6g β-CD, 120g water carried out enclose in ultrasonic 40 minutes.
Demonstration test: carry out demonstration test by above-mentioned definite technology, the results are shown in Figure 7.
Demonstration test result shows: this technology is rationally feasible, has repeatability and operability.
Adopt liquid chromatography to carry out the research of assay:
Fructus Forsythiae has the effect of heat-clearing and toxic substances removing, indispensable main flavour of a drug in the side of being, the content of phillyrin in mensuration antivirus buccal tablet or the chewable tablet.The chromatographic condition of being invented can reach baseline separation, and peak symmetry is good.Done the negative sample of scarce Fructus Forsythiae again by prescription, negative sample is noiseless with phillyrin reference substance chromatograph corresponding position as a result.And having carried out methodological study, the result shows that this method specificity is strong, favorable reproducibility.
Detect wavelength determination: get the phillyrin reference substance and add methanol and be made into reference substance solution.UV scanning in 200～400nm wave-length coverage, the result has absworption peak at 206nm, 229nm, 278nm place, and the 206nm place belongs to end absorption, should not select for use; 229nm wavelength place absworption peak absorbs peak height than 278nm wavelength place, first-selected 229nm wavelength, the blank sample that lacks Fructus Forsythiae again by the prescription preparation, make the test liquid sample introduction, detect at 229nm wavelength place, the result lacks the test liquid of the blank sample of Fructus Forsythiae and locates no absworption peak in the phillyrin peak position, and interference measurement is the detection wavelength so select 229nm.
Determining of mobile phase: select mobile phase for use: (1) acetonitrile-water (25: 75), (2) methanol-acetonitrile-water (15: 20: 73), (3) methanol-acetonitrile-0.1mol/L sodium dihydrogen phosphate (phosphoric acid is transferred PH3.2) (20: 21: 75) test.With Tianjin, island LC-10AT VP high performance liquid chromatograph, detector: Tianjin, island SPD-10A VP, chromatographic column: enlightening horse Diamonsil C18 5 μ 4.6 * 200mm test.As a result mobile phase (1) mobile phase (2) all can, adopt the chromatograph of mobile phase (3), the phillyrin peak reaches baseline separation with adjacent peak, the peak shape symmetry is better, retention time is moderate to be the best.
Select for use the wide methanol of extraction scope to make solvent.Precision takes by weighing sample, and porphyrize adds the methanol supersound extraction, filters, and gets subsequent filtrate and is added on the neutral alumina post, with 70% ethanol 80ml eluting, collects eluent, and evaporate to dryness, residue add 50% methanol makes dissolving, and quantitatively is transferred in the measuring bottle, as need testing solution.
In order to remove redundant impurities, compared following several processing methods: sample thief 6g, precision adds methanol 60ml, and supersound extraction 30 minutes filters, and precision is measured subsequent filtrate 10ml, totally 3 parts, prepares need testing solution respectively as follows.
(1) get macroporous resin column on the methanol extract liquid, use 50% ethanol elution, collect eluent, evaporate to dryness, residue add 50% methanol makes dissolving, and quantitatively is transferred in the 5ml measuring bottle, as need testing solution.
(2) get neutral alumina post on the methanol extract liquid, use 70% ethanol elution, collect eluent, evaporate to dryness, residue add 50% methanol makes dissolving, and quantitatively is transferred in the 5ml measuring bottle, as need testing solution.
(3) get methanol extract liquid and put evaporate to dryness in the water-bath, residue is dissolved in water, with ethyl acetate extraction 3 times, merge ethyl acetate liquid evaporate to dryness and (add ethyl acetate extraction the 4th in addition, it is standby that ethyl acetate liquid is made need testing solution with method), residue adds 50% methanol makes dissolving, and quantitatively is transferred in the 5ml measuring bottle, as need testing solution.
Get each 10 μ l of above-mentioned need testing solution, inject chromatograph of liquid, record chromatogram, relatively the peak area situation at phillyrin peak.
After result of the test, method (1) went up macroporous resin column, impurity lack, and on the method (2) behind the neutral alumina post, impurity has obviously lacked and lost also smallerly, and peak area is apparently higher than method (1), method (3).
Method (3) not only peak area is lost bigger less than method (2).Test liquid with ethyl acetate extraction the 4th time still has tangible peak at place, phillyrin peak position, and peak area is bigger.The results are shown in Figure 8.
Above-mentioned test shows, method (1) and method (2) all can, method (3) goes up alumina column, than last macroporous resin column or effective with ethyl acetate extraction, losing little is the best.
After understanding last alumina column,, done following test again with the effect of 70% ethanol elution.With alumina column on the test liquid, behind 70% ethanol 80ml eluting, use the 40ml70% ethanol elution more in addition, collect eluent, make need testing solution with method, sample introduction 10 μ l, the result occurs at no peak, place, phillyrin peak position, after showing 70% ethanol 80ml eluting, eluting is more complete, and effect is better.
By above test, determine that the need testing solution preparation method is as follows:
The preparation of need testing solution: get 10 of this product, remove film-coat, the accurate title, decided porphyrize, mixing.Precision takes by weighing about 3g, puts in the tool plug conical flask, and the accurate methanol 50ml that adds claims to decide weight, supersound extraction 20 minutes is put coldly, adds methanol and supplies weight, shakes up, filter, precision is measured subsequent filtrate 10ml, is added on 5g neutral alumina post (on 1.0～1.5cm), with 70% ethanol 80ml eluting.Collect eluent, evaporate to dryness, residue add 50% methanol makes dissolving, and is transferred in the 5ml measuring bottle, is diluted to scale, shakes up, and filters, and gets subsequent filtrate high speed centrifugation (more than 8000 rev/mins), gets supernatant as need testing solution.
The investigation of linear relationship: precision takes by weighing phillyrin reference substance 9.92mg, add methanol and be made into phillyrin methanol solution (99.2 μ g/ml), drawing 5ml again adds methanol and is diluted to 10ml, be made into reference substance solution (1) (49.6 μ g/ml), more successively down dilution be made into the reference substance solution that concentration is respectively (2) 24.8 μ g/ml, (3) 12.4 μ g/ml, (4) 6.2 μ g/ml.Get reference substance solution sample introduction 10 μ l respectively, the record chromatogram is measured its peak area.With the peak area value is vertical coordinate, and sample size is abscissa mapping, a straight line, the results are shown in Figure 9, Figure 10.
Experiment shows: this product linear relationship between sample size 0.062～0.992 μ g is good, correlation coefficient r=0.9999.y2003502x+10605。
Quantitative limit: get phillyrin reference substance solution (5) (6.2 a μ g/ml) 3ml, add methanol and be diluted to 50ml, be made into the reference substance solution of 0.372 μ g/ml.The accurate 10 μ l sample introductions of drawing, the record chromatogram is observed phillyrin peak and baseline noise, and its signal to noise ratio is about 10: 1.Sample size is 0.00372 μ g, and this product quantitatively is limited to 3.72ng.
The precision test: accurate phillyrin reference substance solution (24.8 μ g/ml) the 10 μ l that draw, repeat sample introduction 5 times, record the peak area of phillyrin, the relative average debiation of peak area (RSD) is 0.47%, the results are shown in Figure 11.
Experiment shows: this law precision is good.
The application of sample recovery test: precision takes by weighing phillyrin 10.23mg, adds methanol 50ml, is made into the contrast solution that every 1ml contains 0.2046mg; Precision is measured above-mentioned contrast solution 5ml and is added methanol 50ml again, is made into the reference substance solution that every 1ml contains 0.02046mg/ml.
Get 5 of tool plug conical flasks, accurate respectively phillyrin reference substance solution (0.2046mg/ml) 1.0ml, the water bath method of adding, five parts in the accurate again sample (lot number: 020601), content is 0.1397mg/g) that takes by weighing replica test, every part of about 1.5g, put in the tool plug conical flask, each accurate methanol 50ml that adds claims to decide weight, supersound extraction 20 minutes is put coldly, adds methanol and supplies weight, shake up, filter, precision is measured subsequent filtrate 10ml, is added on 5g neutral alumina post (on 1.0～1.5cm), with 70% ethanol 80ml eluting, collect eluent, evaporate to dryness is with 50% dissolve with methanol, and be transferred in the 5ml measuring bottle, be diluted to scale, shake up, filter, get subsequent filtrate, centrifugal (more than 8000 rev/mins) get supernatant, as need testing solution.
Other gets above-mentioned phillyrin contrast solution (0.02046mg/ml) product solution in contrast.
Measure according to this product content assaying method, be calculated as follows the response rate,
The results are shown in Figure 12.
All between 95～105%, meansigma methods is 97.20% to the average recovery measurement result of five tests, and RSD is 1.62%.
Description of drawings Fig. 1 is the experimental factor water-glass.Fig. 2 is the orthogonal experiments table.Fig. 3 is an analysis of variance table.Fig. 4 is the experimental factor water-glass.Fig. 5 is the orthogonal experiments table.Fig. 6 is an analysis of variance table.Fig. 7 is a demonstration test table as a result.Fig. 8 for the identical peak area ratio of pre-treatment difference sample size.Fig. 9 is a canonical plotting.Figure 10 is a reference substance range of linearity measurement result.Figure 11 is a Precision test result.Figure 12 is the recovery test result.
Specific embodiment embodiment one: Radix Isatidis 642.9g, Gypsum Fibrosum 285.7g, Rhizoma Phragmitis 303.6g, Radix Rehmanniae 160.7g, Radix Curcumae 125g, Rhizoma Anemarrhenae 125g, Rhizoma Acori Graminei 125g, Herba Pogostemonis 142.9g, above nine flavors of Fructus Forsythiae 232.1g add right amount of auxiliary materials and make 1000 (1.2g/ sheets) after extracting, making with extra care.
Take by weighing above nine herbal medicines by prescription, decoct with water secondary, add 8 times of amounts for the first time, decoct 1.5 hours (collect volatile oil, it is standby that volatile oil emulsion redistillation gets volatile oil); For the second time add 6 times of amounts, decocted 1 hour 20 minutes, collecting decoction, medicinal liquid are concentrated into 1250ml after crossing 200 mesh sieves; Add 90% ethanol 2500ml and make medicinal liquid contain alcohol amount to reach 60% and make precipitation, leave standstill more than 12 hours, filter, behind decompression filtrate recycling ethanol, the extractum that is evaporated to relative density and is 1.16-1.18 (80 ℃ of surveys) is standby; Volatile oil carries out ultrasonic enclose in right amount with β-CD, sucking filtration, and 40 ℃ of dryings 4 hours are ground, and cross 80 mesh sieves, and are standby.Carry out fluidized-bed spray granulation with an amount of soluble starch, lactose, aspartame and volatile oil beta-CD inclusion mixing.Granule is being about 5%, 20 order and 100 mesh sieve granulate in dry to moisture below 80 ℃.Qualified granule adds 0.5% magnesium stearate mixing, presses 1.2g/ sheet tabletting, coating, and packing promptly gets antivirus buccal tablet or chews.
Assay:
Chromatographic condition and system suitability test octadecylsilane chemically bonded silica are filler: and acetonitrile-0.1mol/L biphosphate receives (phosphoric acid transfer pH to 3.2)-and methanol (21: 75: 20) is mobile phase; The detection wavelength is 229nm.Number of theoretical plate calculates by the phillyrin peak should be not less than 3000.
It is an amount of that the preparation precision of reference substance solution takes by weighing phillyrin, adds methanol and be diluted to the solution that every 1ml contains 0.02mg, in contrast product solution.
10 of this product are got in the preparation of need testing solution, and accurate the title decides.Porphyrize, mixing is got about 3g, the accurate title, decide, and puts in the tool plug conical flask, the accurate methanol 50ml that adds, claim to decide weight, supersound extraction 20 minutes is put cold, add methanol and supply weight, shake up, filter, precision is measured subsequent filtrate 10ml, be added on 5g neutral alumina post (on 1.0～1.5cm), with 70% ethanol 80ml eluting, collect eluent, evaporate to dryness, with 50% dissolve with methanol and be transferred in the 5ml measuring bottle, be diluted to scale, shake up, filter, get subsequent filtrate centrifugal (more than 8000 rev/mins), get supernatant as need testing solution.
Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject high performance liquid chromatograph, measure, and every of this product contains Fructus Forsythiae with phillyrin (C
29H
36O
15) meter, be 0.18mg..
Embodiment two: Radix Isatidis 640g, Gypsum Fibrosum 284g, Rhizoma Phragmitis 300g, Radix Rehmanniae 158g, Radix Curcumae 124g, Rhizoma Anemarrhenae 124g, Rhizoma Acori Graminei 124g, Herba Pogostemonis 140g, above nine flavors of Fructus Forsythiae 230g add right amount of auxiliary materials and make 1000 (1.2g/ sheets) after extracting, making with extra care.
Take by weighing above nine herbal medicines by prescription, decoct with water secondary, add 8 times of amounts for the first time, decoct 1.5 hours (collect volatile oil, it is standby that volatile oil emulsion redistillation gets volatile oil); For the second time add 6 times of amounts, decocted 1 hour 20 minutes, collecting decoction, medicinal liquid are concentrated into 1250ml after crossing 200 mesh sieves; Add 90% ethanol 2500ml and make medicinal liquid contain alcohol amount to reach 60% and make precipitation, leave standstill more than 12 hours, filter, behind decompression filtrate recycling ethanol, the extractum that is evaporated to relative density and is 1.16-1.18 (80 ℃ of surveys) is standby; Volatile oil carries out ultrasonic enclose in right amount with β-CD, sucking filtration, and 40 ℃ of dryings 4 hours are ground, and cross 80 mesh sieves, and are standby.Carry out fluidized-bed spray granulation with an amount of soluble starch, lactose, aspartame and volatile oil beta-CD inclusion mixing.Granule is about 5%, 20 order and 100 mesh sieve granulate being dried to moisture below 80 ℃.Qualified granule adds 0.5% magnesium stearate mixing, presses 1.2g/ sheet tabletting, coating, and packing promptly gets antivirus buccal tablet or chews.
Measure with embodiment one described liquid chromatography (but using eight carbon alkyl silane bonded silica gels to be filler), every of this product contains Fructus Forsythiae with phillyrin (C
29H
36O
15) meter, be 0.09mg..
Embodiment three: Radix Isatidis 645g, Gypsum Fibrosum 287g, Rhizoma Phragmitis 305g, Radix Rehmanniae 162g, Radix Curcumae 126g, Rhizoma Anemarrhenae 126g, Rhizoma Acori Graminei 126g, Herba Pogostemonis 145g, above nine flavors of Fructus Forsythiae 234g add right amount of auxiliary materials and make 1000 (1.2g/ sheets) after extracting, making with extra care.
Take by weighing above nine herbal medicines by prescription, decoct with water secondary, add 10 times of amounts for the first time, decoct 2.5 hours (collect volatile oil, it is standby that volatile oil emulsion redistillation gets volatile oil); For the second time add 4 times of amounts, decocted 0.5 hour, collecting decoction, medicinal liquid are concentrated into 1000ml after crossing 100 mesh sieves; Add 80% ethanol 3000ml and make medicinal liquid contain alcohol amount to reach 70% and make precipitation, leave standstill more than 6 hours, filter, behind decompression filtrate recycling ethanol, the extractum that is evaporated to relative density and is 1.16-1.18 (80 ℃ of surveys) is standby; Volatile oil carries out ultrasonic enclose in right amount with porous-starch or maltodextrin, sucking filtration, and 40 ℃ of dryings 4 hours are ground, and cross 80 mesh sieves, and are standby.Carry out fluidized-bed spray granulation with an amount of soluble starch, lactose, aspartame and volatile oil clathrate compound mixing.Granule is about 5%, 20 order and 100 mesh sieve granulate being dried to moisture below 80 ℃.Qualified granule adds 0.5% magnesium stearate mixing, presses 1.2g/ sheet tabletting, coating, and packing promptly gets antivirus buccal tablet or chews.
With embodiment one described liquid chromatography for measuring, every of this product contains Fructus Forsythiae with phillyrin (C
29H
36O
15) meter, be 0.06mg.
Set forth below good effect of the present invention:
Modern medicine thinks that the epithelial cell of respiratory tract and oral mucosa is the main position of influenza virus invasion, and influenza virus is main By the air droplet infection, the spittle mainly is derived from the saliva in the influenza patient's mouth, therefore is necessary development from source cut-out pathogeny, Pay attention to the formulation of prevention. Buccal tablet or chewable tablet, slowly dissolving in the oral cavity produces the preventive and therapeutic effect except absorbing by mucous membrane, The saliva of containing the drug-eluting composition absorbs produce effects by swallowing directly to enter in the stomach. Buccal tablet is applicable to the old age of dysphagia Patient and weakling's medication especially are subjected to liking of children; Buccal tablet is compared with oral liquid, and infiltration rate is substantially suitable, and does not contain Any anticorrisive agent is easy to carry, and stability better is beneficial to storage. Therefore, anti-virus sucking tablets or chewable tablets have satisfied clinical The needs that multiple medication is selected.
Antivirus buccal tablet or chewable tablets have adopted advanced preparation technique in preparation technology, become with β one cyclodextrin encapsulated volatility Divide, to guarantee the stability of volatile ingredient.
Its main active ingredient forsythin is one of antiviral active ingredient, and its content adopts liquid chromatography for measuring, can be accurate Measure the limit of forsythin in anti-virus sucking tablets of the present invention or the chewable tablets, realized the quality controllable purpose of Chinese medicine.
For satisfying diabetes patient's medication needs, auxiliary material and the flavouring of screening are non-sugared type meticulously, thereby the mouthfeel of lozenge Good, existing Radix Isatidis, the sweetness of reed rhizome and the capsule of weeping forsythia is bitter taste slightly, Pogostemon cablin is arranged again, the hot fragrance of orpiment Pu. So, popular The high-incidence season of venereal disease poison, antiviral oral buccal tablet or chewable tablets are used for the treatment of and prevent epidemic virus flu, viral influenza, flu It is an extraordinary selection.
Claims (16)
1. an antivirus buccal tablet or an antivirus chewing tablet of being made by Radix Isatidis, Gypsum Fibrosum, Rhizoma Phragmitis, Radix Rehmanniae, Radix Curcumae, the Rhizoma Anemarrhenae, Rhizoma Acori Graminei, Herba Pogostemonis, Fructus Forsythiae combination is characterized in that
A: the combination ratio of each medicine is
Radix Isatidis 600-700g Gypsum Fibrosum 250-300g Rhizoma Phragmitis 275-325g
Radix Rehmanniae 140-180g Radix Curcumae 100-150g Rhizoma Anemarrhenae 100-150g
Rhizoma Acori Graminei 100-150g Herba Pogostemonis 120-160g Fructus Forsythiae 200-260g
B: above nine herbal medicines, decoct with water, concentrate; Add ethanol, leave standstill, filter, behind filtrate recycling ethanol, concentrate and obtain extractum;
C: concentrate the extractum that obtains and be equipped with an amount of suitable excipient and correctives, granulate.Drying, compacting promptly gets antivirus buccal tablet or antivirus chewing tablet in flakes.
2. antivirus buccal tablet according to claim 1 or antivirus chewing tablet, preferable combination ratio between its each medicine
Radix Isatidis 640-645g Gypsum Fibrosum 284-287g Rhizoma Phragmitis 300-305g
Radix Rehmanniae 158-162g Radix Curcumae 124-126g Rhizoma Anemarrhenae 124-126g
Rhizoma Acori Graminei 124-126g Herba Pogostemonis 140-145g Fructus Forsythiae 230-234g
3. anti-viral pharmaceutical compositions according to claim 1, best of breed ratio between its each medicine
Radix Isatidis 642.9g Gypsum Fibrosum 285.7g Rhizoma Phragmitis 303.6g
Radix Rehmanniae 160.7g Radix Curcumae 125g Rhizoma Anemarrhenae 125g
Rhizoma Acori Graminei 125g Herba Pogostemonis 142.9g Fructus Forsythiae 232.1g
4. according to claim 1 and 2 described antivirus buccal tablet or antivirus chewing tablets, its compositions decocts with water secondary, adds 6-10 for the first time and doubly measures, and decocts 0.5-2.5 hour; For the second time add 4-8 and doubly measure, decocted 0.5-2.5 hour, collecting decoction, medicinal liquid concentrate after crossing the 60-200 mesh sieve; Add ethanol and make precipitation, leave standstill, filter, behind filtrate recycling ethanol, be concentrated into the extractum that relative density is 1.00-1.300.Granulate with an amount of excipient and correctives.Drying, granulate.Tabletting, promptly.
5. according to claim 1 and 3 described antivirus buccal tablet or antivirus chewing tablets, its compositions decocts with water secondary, adds 6-10 for the first time and doubly measures, and decocts 0.5-2.5 hour; For the second time add 4-8 and doubly measure, decocted 0.5-2.5 hour, collecting decoction, medicinal liquid concentrate after crossing the 60-200 mesh sieve; Add ethanol and make precipitation, leave standstill, filter, behind filtrate recycling ethanol, be concentrated into the extractum that relative density is 1.00-1.300.Granulate with an amount of excipient and correctives.Drying, granulate.Tabletting promptly.
6. claim 4 and 5 described excipient are starch, soluble starch, lactose, mannitol, maltodextrin, are the best with soluble starch and lactose.
7. claim 4 and 5 described correctivess are aspartame, glucide, steviol glycosides, citric acid, essence, Herba Menthae and Oleum menthae, are best with the aspartame.
8. according to claim 1 and 4 described antivirus buccal tablet or antivirus chewing tablets, adopt liquid chromatography for measuring index composition or active ingredient lotus to stick up the content of glycosides.
9. according to claim 1 and 5 described antivirus buccal tablet or antivirus chewing tablets, adopt liquid chromatography for measuring index composition or active ingredient lotus to stick up the content of glycosides.
According to Claim 8 with 9 described antivirus buccal tablet or antivirus chewing tablets, its described liquid chromatography is
A: the test of chromatographic condition and system suitability is for being filler with 8 carbon alkyl to the alkyl linked silica gel of 18 carbon; Acetonitrile-biphosphate receives (phosphoric acid transfer pH to 2.5-4.0)-and methanol is mobile phase; The detection wavelength is 220-240nm.Number of theoretical plate calculates by the phillyrin peak should be not less than 800.
B: need testing solution preparation: get this product and add methanol extraction, precision is measured extracting solution, is added on the neutral alumina post, with ethanol elution, collects eluent, evaporate to dryness with dissolve with methanol, and is transferred in the measuring bottle, is diluted to scale, shakes up, filter, it is centrifugal to get subsequent filtrate, gets supernatant, promptly.
C: the reference substance solution preparation: it is an amount of to get phillyrin, adds methanol and is diluted to, in contrast product solution.
D: algoscopy: accurate respectively reference substance solution and the need testing solution drawn, inject high performance liquid chromatograph, measure and calculate promptly.
Every of this product contains Fructus Forsythiae with phillyrin (C
29H
36O
15) meter, must not be less than 0.03mg.
11. an anti-viral pharmaceutical compositions of being made up of Radix Isatidis, Gypsum Fibrosum, Rhizoma Phragmitis, Radix Rehmanniae, Radix Curcumae, the Rhizoma Anemarrhenae, Rhizoma Acori Graminei, Herba Pogostemonis, Fructus Forsythiae prepares the preparation technology of antivirus buccal tablet or antivirus chewing tablet medicine, it is characterized in that
A: when decocting with water, collect volatile oil,
B: volatile oil carries out enclose in right amount with the hole excipient.
12. according to the preparation technology of the described anti-viral pharmaceutical compositions of claim 11, its collected volatile oil comprises volatile oil emulsion, and volatile oil emulsion redistillation is got volatile oil.
13. according to the preparation technology of the described anti-viral pharmaceutical compositions of claim 11, it is beta-schardinger dextrin-with porous crack excipient that its collected volatile oil carries out enclose, maltodextrin, and porous crack starch or macrovoid starch etc. are best with the beta-schardinger dextrin-.
14. according to the preparation technology of claim 11 and 13 described anti-viral pharmaceutical compositions, when its collected volatile oil carries out enclose with ultrasonic bag be the best.
15. the preparation technology of anti-viral pharmaceutical compositions according to claim 11 adopts liquid chromatography for measuring index composition or active ingredient lotus to stick up the content of glycosides.
16. its index composition of the preparation process of anti-viral pharmaceutical compositions according to claim 15 and gained drug detection or active ingredient lotus stick up the liquid chromatography of the content employing of glycosides
A: the test of chromatographic condition and system suitability is for being filler with 8 carbon alkyl to the alkyl linked silica gel of 18 carbon; Acetonitrile-biphosphate receives (phosphoric acid transfer pH to 2.5-4.0)-and methanol is mobile phase; The detection wavelength is 220-240nm.Number of theoretical plate calculates by the phillyrin peak should be not less than 800.
B: need testing solution preparation: get this product and add methanol extraction, precision is measured extracting solution, is added on the neutral alumina post, with ethanol elution, collects eluent, evaporate to dryness with dissolve with methanol, and is transferred in the measuring bottle, is diluted to scale, shakes up, filter, it is centrifugal to get subsequent filtrate, gets supernatant, promptly.
C: the reference substance solution preparation: it is an amount of to get phillyrin, adds methanol and is diluted to, in contrast product solution.
D: algoscopy: accurate respectively reference substance solution and the need testing solution drawn, inject high performance liquid chromatograph, measure and calculate promptly.
Every of this product contains Fructus Forsythiae with phillyrin (C
29H
36O
15) meter, must not be less than 0.03mg.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200410040669 CN1748776A (en) | 2004-09-13 | 2004-09-13 | Anti-virus lozenge or anti-virus chewing tablet and its preparing method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410040669 CN1748776A (en) | 2004-09-13 | 2004-09-13 | Anti-virus lozenge or anti-virus chewing tablet and its preparing method |
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| CN1748776A true CN1748776A (en) | 2006-03-22 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103675189A (en) * | 2012-09-05 | 2014-03-26 | 亚宝药业集团股份有限公司 | Quality detection method for fructus forsythiae leaf medicinal materials |
| CN103736039A (en) * | 2013-11-22 | 2014-04-23 | 镇江市丹徒区南山溪园茶叶专业合作社 | Chewable tablet beneficial to cold prevention |
| WO2016019684A1 (en) * | 2014-08-07 | 2016-02-11 | 富力 | Applications of phillyrin/phillygenin composition in preparing drugs or health care products for relieving and/or treating viral diseases |
-
2004
- 2004-09-13 CN CN 200410040669 patent/CN1748776A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103675189A (en) * | 2012-09-05 | 2014-03-26 | 亚宝药业集团股份有限公司 | Quality detection method for fructus forsythiae leaf medicinal materials |
| CN103675189B (en) * | 2012-09-05 | 2016-06-29 | 亚宝药业集团股份有限公司 | A kind of quality determining method of Folium Forsythiae medical material |
| CN103736039A (en) * | 2013-11-22 | 2014-04-23 | 镇江市丹徒区南山溪园茶叶专业合作社 | Chewable tablet beneficial to cold prevention |
| WO2016019684A1 (en) * | 2014-08-07 | 2016-02-11 | 富力 | Applications of phillyrin/phillygenin composition in preparing drugs or health care products for relieving and/or treating viral diseases |
| JP2017523191A (en) * | 2014-08-07 | 2017-08-17 | 富力 | Application of fililine / filigenin composition in the preparation of drugs or health care products for the reduction and / or treatment of viral diseases, and drugs or health care products for the treatment of viral diseases |
| RU2655616C1 (en) * | 2014-08-07 | 2018-05-29 | Ли ФУ | Application of phillyrin/phillygenin composition when preparing a medicament or medical product for the relief and/or treatment of viral diseases and medicament or medical product for treatment of viral diseases |
| AU2014402938B2 (en) * | 2014-08-07 | 2019-02-14 | Li Fu | Applications of phillyrin/phillygenin composition in preparing drugs or health care products for relieving and/or treating viral diseases |
| US10286002B2 (en) | 2014-08-07 | 2019-05-14 | Li Fu | Application of a phillyrin/phillygeninin composition in preparing a medicine or health care product for alleviating or/and treating viral diseases, and medicine or health care product for treating viral diseases |
| US10881679B2 (en) | 2014-08-07 | 2021-01-05 | Li Fu | Application of a phillyrin/phillygeninin composition in preparing a medicine or health care product for alleviating or/and treating viral diseases, and medicine or health care product for treating viral diseases |
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