Summary of the invention
For solving not easy-formation of Chinese medicine effervescent tablet, disintegrate is slow, and clarity is bad, and problems such as poor stability the invention provides a kind of principal agent, supplementary product kind reasonable mixture ratio, forming, heat-clearing and detoxicating effervescence tablet of good stability and preparation method thereof.
The present invention is implemented by the following technical programs.
A kind of heat-clearing and detoxicating effervescence tablet of the present invention, it is made up of following components by part by weight:
Heat-clearing and toxic substances removing extract powder, tartaric acid, sodium bicarbonate are 92-99 part altogether, heat-clearing and toxic substances removing extract powder: tartaric acid: sodium bicarbonate is 1: 1: 1, filler 0-5 part, lubricant 0.5-1 part, sweeting agent 0.5-2 part.
Wherein said heat-clearing and toxic substances removing extract powder is made by weight by following raw material:
Gypsum Fibrosum 10 Flos Loniceraes 2 Radix Scrophulariaes 1.6 Radix Rehmanniae 1.2 Fructus Forsythiaes 1 Fructus Gardeniae 1
0.8 Radix Ophiopogonis 0.8 of Herba Gueldenstaedtiae 1 Radix Scutellariae 1 Radix Gentianae 1 Radix Isatidis 1 Rhizoma Anemarrhenae
Sweeting agent is selected from a kind of of stevioside, betanin, Aspartane, is preferably Aspartane; Filler is selected from a kind of in lactose, mannitol, the xylitol, is preferably mannitol, xylitol; Lubricant is selected from a kind of in polyethylene glycol 6000, Macrogol 4000, the magnesium stearate.
Its preparation method can be mainly to comprise following process steps:
(1) ten two flavor medical material, except that Flos Lonicerae, Radix Scutellariae, ten flavors such as all the other Gypsum Fibrosum add 8-12 times of water gaging warm macerating 1 hour earlier, decoct secondary, after waiting to seethe with excitement, cold rnning Flos Lonicerae and Radix Scutellariae slightly, 1 hour for the first time, 40 minutes for the second time, filter merging filtrate, it is 1.17 that filtrate is concentrated into 60 ℃ of surveys of relative density, add ethanol, make to contain the alcohol amount and reach 65%~70%, cold preservation 48 hours, filter, reclaim ethanol, add 0.5% active carbon, heated 30 minutes, filter, filtrate is concentrated into and is determined as 1.25~1.30 thick paste under 60 ℃ of the relative densities, and drying under reduced pressure is ground into fine powder.
(2) the equal 80 ℃ of oven dry of used adjuvant in the prescription, sieving for standby; Heat-clearing and toxic substances removing extractum fine powder and tartaric acid, sodium bicarbonate, sweeting agent, filler are carried out proportion optimization by the umber of above-mentioned each component of effervescent tablet, to determine optimum formula.Filler is used for regulating total amount, and sweeting agent is used for improving mouthfeel, and lubricant plays fluidizer and lubrication when tabletting.
Below be heat-clearing and detoxicating effervescence tablet prescription screening experiment:
One, the selection of sour agent and alkaline agent
In the selection of effervescent, sodium bicarbonate is as carbon source, and consumption is few, and gas production is big, and the present invention adopts sodium bicarbonate as carbon source.Because the easy moisture absorption of Chinese medical concrete powder, viscosity is big, so the selection of acid source is very important.Take by weighing a certain amount of medicated powder and mix evenly, granulate, carry out different preparations shaping prescriptions and screen, the results are shown in Table 1 with dehydrated alcohol with acid, alkali.
The screening of the different preparations shaping soda acid of table 1 prescription
The prescription number |
Medicated powder (g) |
Acid kind (g) |
Alkali kind (g) |
The result |
1 2 3 4 5 6 |
14 14 14 14 14 14 |
Tartaric acid 14 adipic acids 14 succinic acid 14 malic acids 14 fumaric acid 14 citric acids 14 |
Sodium bicarbonate 14 sodium bicarbonate 14 sodium bicarbonate 14 sodium bicarbonate 14 sodium bicarbonate 14 sodium bicarbonate 14 |
The all good effervescent of granulation, tabletting, effervescent is too slow, the bad moisture absorption of effect, the moisture absorption of can't granulating, can't granulate better, effervescent lumps slowly, can't granulate |
The result shows: the effect of prescription 1 is better, and promptly the preferred tartaric acid of effervescent is as acid source, and sodium bicarbonate is as carbon source.
Two, medicated powder, the screening of effervescent proportioning
To effervescent tablet quality influence maximum in the Chinese medicine effervescent tablet is soda acid ratio in effervescent and drug ratios and the effervescent, be screening formula, based on above-mentioned prescription 1, be factor in soda acid ratio in the ratio of shared weight of effervescent and the effervescent, do 4 horizontal comprehensive tests.
Test method: get the not commensurability medicated powder and the soda acid of different proportionings (the prescription total amount is 45g) respectively, evenly mixed, granulate with dehydrated alcohol, drying, tabletting the results are shown in Table 2.
Table 2 medicated powder, effervescent proportioning screening table
Sequence number |
Medicated powder accounts for sheet anharmonic ratio example |
Effervescent accounts for sheet anharmonic ratio example |
Acid accounts for the effervescent ratio |
The effervescent effect |
Disintegration time (branch) |
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 |
1/3 1/3 1/3 1/3 2/5 2/5 2/5 2/5 1/2 1/2 1/2 1/2 3/5 3/5 3/5 3/5 |
2/3 2/3 2/3 2/3 3/5 3/5 3/5 3/5 1/2 1/2 1/2 1/2 2/5 2/5 2/5 2/5 |
40% 45% 50% 55% 40% 45% 50% 55% 40% 45% 50% 55% 40% 45% 50% 55% |
+++ ++++ ++++ +++ +++ +++ +++ +++ ++ ++ ++ ++ + + + + |
Exceeded in 1 minute 1.1 1.2 2.1 4.4 4.4 4.6 4.7 to exceed in limited time to exceed in limited time to exceed in limited time to exceed in limited time to exceed in limited time to exceed in limited time and exceed in limited time in limited time |
Comprehensive relatively, effervescent effect 2,3,4,5,6,7,8 all can, 1 gas release is too big, 5,6,7,8 a little less than, 2,3 prescription gas releases are moderate, disintegrate is very fast, is that the soda acid proportioning is further groped on the basis with 2,3 prescriptions.
Three, effervescent consumption screening
Know according to above-mentioned result of the test, effervescent tablet of the present invention is promptly plastic without filler, consider that different batches Chinese crude drug paste-forming rate is variant in the production, need there be 0-5% filler space to regulate total amount, simultaneously for improving mouthfeel, the sweeting agent that can add 0.5-2%, particulate flowability when increasing tabletting can add the lubricant of 0.5-1%.
Test method: every group of test all feeds intake by 100, take by weighing prescription dried cream powder 145g, add not commensurability tartaric acid, sodium bicarbonate and an amount of filler, sweeting agent mixing, with dehydrated alcohol granulation, drying, add lubricant, mixing, tabletting, every heavy 4.5g/ sheet the results are shown in following table, the consumption during the consumption of table Chinese medicine powder, acid, alkali is every.
Table 3 effervescent consumption screening table
Sequence number |
Medicated powder (g) |
Acid (g) |
Alkali (g) |
Disintegration time |
Medicinal liquid evaluation behind the effervescent |
12 |
1.45 1.45 |
1.31 1.38 |
1.59 1.52 |
1 minute 40 seconds 1 minute 42 seconds |
Medicinal liquid has a small amount of floccule, and mouthfeel is general.Medicinal liquid has a small amount of floccule, and mouthfeel is general. |
3 |
1.45 |
1.45 |
1.45 |
1 minute 50 seconds |
The medicinal liquid clarification, mouthfeel is good. |
4 |
1.45 |
1.51 |
1.39 |
1 minute 12 seconds |
Medicinal liquid is muddy slightly, and mouthfeel is general. |
Table 3 result of the test shows, effervescent tablet of the present invention with medicated powder, tartaric acid, sodium bicarbonate be 1: 1: 1 be best proportion.
Four, moulding process study on the stability
In order to investigate the stability of moulding process, we place 40 ℃, relative humidity with the effervescent tablet of two aluminum laminated films packings is 75% climatic chamber, places 1 month, takes out, and measures appearance character, the variation of effervescent time before and after its test, the results are shown in Table 7.
Comparing result before and after table 4 accelerated test
Sample |
Appearance character |
The effervescent time |
After testing before the test |
Sepia tablet sepia tablet |
1 minute 55 seconds 1 minute 48 seconds |
The result shows: this medicine has no significant change at aspects such as appearance color, physical behavior, effervescent times before and after the accelerated test, illustrates that this medicine is basicly stable, and moulding process is reasonable.
It is reasonable that heat-clearing and detoxicating effervescence tablet principal agent of the present invention, adjuvant are formed with the proportioning selection, and effervescent is effective, is homogeneous solution behind the effervescent.The heat-clearing and detoxicating effervescence tablet preparation technology who makes by the present invention is simple, steady quality.
The specific embodiment
The present invention is described further by embodiment.
Embodiment 1
According to the shared umber of each raw material in the heat-clearing and detoxicating effervescence tablet, it is standby to get following recipe quantity raw material (by the gram number):
Gypsum Fibrosum 6700g Flos Lonicerae 1340g Radix Scrophulariae 1070g Radix Rehmanniae 800g Fructus Forsythiae 670g Fructus Gardeniae 670g
Herba Gueldenstaedtiae 670g Radix Scutellariae 670g Radix Gentianae 670g Radix Isatidis 670g Rhizoma Anemarrhenae 540g 540g Radix Ophiopogonis
The heat-clearing and detoxicating effervescence tablet preparation method comprises following process steps:
(1) ten two flavor medical material removes Flos Lonicerae, outside the Radix Scutellariae, ten flavors such as all the other Gypsum Fibrosum add 10 times of water gaging warm macerating 1 hour earlier, decoct secondary, after waiting to seethe with excitement, cold rnning Flos Lonicerae and Radix Scutellariae slightly, 1 hour for the first time, 40 minutes for the second time, filter, merging filtrate, it is 1.17 that filtrate is concentrated into 60 ℃ of surveys of relative density, adds ethanol, makes to contain the alcohol amount and reach 65%~700%, cold preservation 48 hours, filter, reclaim ethanol, add 0.5% active carbon, heated 30 minutes, filter, filtrate is concentrated into and is determined as 1.25~1.30 thick paste under 60 ℃ of the relative densities, drying under reduced pressure, be ground into fine powder, get heat-clearing and toxic substances removing extract powder 1380g.
(2) the equal 80 ℃ of oven dry of used adjuvant in the prescription, sieving for standby; With recipe quantity heat-clearing and toxic substances removing extractum fine powder 1380g and tartaric acid 1380g, sodium bicarbonate 1380g, A Sibapatan 90g, lactose 225g mixing, with dehydrated alcohol granulate, drying, add PEG4000 45g mixing, be pressed into 1000, promptly.
Embodiment 2
According to the shared umber of each raw material in the heat-clearing and detoxicating effervescence tablet, it is standby to get following recipe quantity raw material (by the gram number):
Gypsum Fibrosum 6700g Flos Lonicerae 1340g Radix Scrophulariae 1070g Radix Rehmanniae 800g Fructus Forsythiae 670g Fructus Gardeniae 670g
Herba Gueldenstaedtiae 670g Radix Scutellariae 670g Radix Gentianae 670g Radix Isatidis 670g Rhizoma Anemarrhenae 540g 540g Radix Ophiopogonis
The heat-clearing and detoxicating effervescence tablet preparation method comprises following process steps:
(1) ten two flavor medical material removes Flos Lonicerae, outside the Radix Scutellariae, ten flavors such as all the other Gypsum Fibrosum add 10 times of water gaging warm macerating 1 hour earlier, decoct secondary, after waiting to seethe with excitement, cold rnning Flos Lonicerae and Radix Scutellariae slightly, 1 hour for the first time, 40 minutes for the second time, filter, merging filtrate, it is 1.17 that filtrate is concentrated into 60 ℃ of surveys of relative density, adds ethanol, makes to contain the alcohol amount and reach 65%~70%, cold preservation 48 hours, filter, reclaim ethanol, add 0.5% active carbon, heated 30 minutes, filter, filtrate is concentrated into and is determined as 1.25~1.30 thick paste under 60 ℃ of the relative densities, drying under reduced pressure, be ground into fine powder, get heat-clearing and toxic substances removing extract powder 1485g.
(2) the equal 80 ℃ of oven dry of used adjuvant in the prescription, sieving for standby; With recipe quantity heat-clearing and toxic substances removing extractum fine powder 1485g and tartaric acid 1485g, sodium bicarbonate 1485g, betanin 22.5g mixing, with dehydrated alcohol granulate, drying, add PEG6000 22.5g mixing, be pressed into 1000, promptly.
Embodiment 3
According to the shared umber of each raw material in the heat-clearing and detoxicating effervescence tablet, it is standby to get following recipe quantity raw material (by the gram number):
Gypsum Fibrosum 6700g Flos Lonicerae 1340g Radix Scrophulariae 1070g Radix Rehmanniae 800g Fructus Forsythiae 670g Fructus Gardeniae 670g
Herba Gueldenstaedtiae 670g Radix Scutellariae 670g Radix Gentianae 670g Radix Isatidis 670g Rhizoma Anemarrhenae 540g 540g Radix Ophiopogonis
The heat-clearing and detoxicating effervescence tablet preparation method comprises following process steps:
(1) ten two flavor medical material removes Flos Lonicerae, outside the Radix Scutellariae, ten flavors such as all the other Gypsum Fibrosum add 10 times of water gaging warm macerating 1 hour earlier, decoct secondary, after waiting to seethe with excitement, cold rnning Flos Lonicerae and Radix Scutellariae slightly, 1 hour for the first time, 40 minutes for the second time, filter, merging filtrate, it is 1.17 that filtrate is concentrated into 60 ℃ of surveys of relative density, adds ethanol, makes to contain the alcohol amount and reach 65%~70%, cold preservation 48 hours, filter, reclaim ethanol, add 0.5% active carbon, heated 30 minutes, filter, filtrate is concentrated into and is determined as 1.25~1.30 thick paste under 60 ℃ of the relative densities, drying under reduced pressure, be ground into fine powder, get heat-clearing and toxic substances removing extract powder 1433g.
(2) the equal 80 ℃ of oven dry of used adjuvant in the prescription, sieving for standby; With recipe quantity heat-clearing and toxic substances removing extractum fine powder 1433g and tartaric acid 1433g, sodium bicarbonate 1433g, stevioside 45g, xylitol 112.5g mixing, with dehydrated alcohol granulate, drying, add magnesium stearate 43.5g mixing, be pressed into 1000, promptly.
Embodiment 4
According to the shared umber of each raw material in the heat-clearing and detoxicating effervescence tablet, it is standby to get following recipe quantity raw material (by the gram number):
Gypsum Fibrosum 6700g Flos Lonicerae 1340g Radix Scrophulariae 1070g Radix Rehmanniae 800g Fructus Forsythiae 670g Fructus Gardeniae 670g
Herba Gueldenstaedtiae 670g Radix Scutellariae 670g Radix Gentianae 670g Radix Isatidis 670g Rhizoma Anemarrhenae 540g 540g Radix Ophiopogonis
The heat-clearing and detoxicating effervescence tablet preparation method comprises following process steps:
(1) ten two flavor medical material removes Flos Lonicerae, outside the Radix Scutellariae, ten flavors such as all the other Gypsum Fibrosum add 10 times of water gaging warm macerating 1 hour earlier, decoct secondary, after waiting to seethe with excitement, cold rnning Flos Lonicerae and Radix Scutellariae slightly, 1 hour for the first time, 40 minutes for the second time, filter, merging filtrate, it is 1.17 that filtrate is concentrated into 60 ℃ of surveys of relative density, adds ethanol, makes to contain the alcohol amount and reach 65%~70%, cold preservation 48 hours, filter, reclaim ethanol, add 0.5% active carbon, heated 30 minutes, filter, filtrate is concentrated into and is determined as 1.25~1.30 thick paste under 60 ℃ of the relative densities, drying under reduced pressure, be ground into fine powder, get heat-clearing and toxic substances removing extract powder 1410g.
(2) the equal 80 ℃ of oven dry of used adjuvant in the prescription, sieving for standby; With recipe quantity heat-clearing and toxic substances removing extractum fine powder 1410g and tartaric acid 1410g, sodium bicarbonate 1410g, A Sibapatan 34g, mannitol 198g mixing, with dehydrated alcohol granulate, drying, add PEG4000 38g mixing, be pressed into 1000, promptly.
Embodiment 5
According to the shared umber of each raw material in the heat-clearing and detoxicating effervescence tablet, it is standby to get following recipe quantity raw material (by the gram number):
Gypsum Fibrosum 6700g Flos Lonicerae 1340g Radix Scrophulariae 1070g Radix Rehmanniae 800g Fructus Forsythiae 670g Fructus Gardeniae 670g
Herba Gueldenstaedtiae 670g Radix Scutellariae 670g Radix Gentianae 670g Radix Isatidis 670g Rhizoma Anemarrhenae 540g 540g Radix Ophiopogonis
The heat-clearing and detoxicating effervescence tablet preparation method comprises following process steps:
(1) ten two flavor medical material removes Flos Lonicerae, outside the Radix Scutellariae, ten flavors such as all the other Gypsum Fibrosum add 10 times of water gaging warm macerating 1 hour earlier, decoct secondary, after waiting to seethe with excitement, cold rnning Flos Lonicerae and Radix Scutellariae slightly, 1 hour for the first time, 40 minutes for the second time, filter, merging filtrate, it is 1.17 that filtrate is concentrated into 60 ℃ of surveys of relative density, adds ethanol, makes to contain the alcohol amount and reach 65%~70%, cold preservation 48 hours, filter, reclaim ethanol, add 0.5% active carbon, heated 30 minutes, filter, filtrate is concentrated into and is determined as 1.25~1.30 thick paste under 60 ℃ of the relative densities, drying under reduced pressure, be ground into fine powder, get heat-clearing and toxic substances removing extract powder 1395g.
(2) the equal 80 ℃ of oven dry of used adjuvant in the prescription, sieving for standby; With recipe quantity heat-clearing and toxic substances removing extractum fine powder 1395g and tartaric acid 1395g, sodium bicarbonate 1395g, A Sibapatan 56.25g, lactose 218.25g mixing, with dehydrated alcohol granulate, drying, add magnesium stearate 40.5g mixing, be pressed into 1000, promptly.
Embodiment 6
According to the shared umber of each raw material in the heat-clearing and detoxicating effervescence tablet, it is standby to get following recipe quantity raw material (by the gram number):
Gypsum Fibrosum 6700g Flos Lonicerae 1340g Radix Scrophulariae 1070g Radix Rehmanniae 800g Fructus Forsythiae 670g Fructus Gardeniae 670g
Herba Gueldenstaedtiae 670g Radix Scutellariae 670g Radix Gentianae 670g Radix Isatidis 670g Rhizoma Anemarrhenae 540g 540g Radix Ophiopogonis
The heat-clearing and detoxicating effervescence tablet preparation method comprises following process steps:
(1) ten two flavor medical material removes Flos Lonicerae, outside the Radix Scutellariae, ten flavors such as all the other Gypsum Fibrosum add 10 times of water gaging warm macerating 1 hour earlier, decoct secondary, after waiting to seethe with excitement, cold rnning Flos Lonicerae and Radix Scutellariae slightly, 1 hour for the first time, 40 minutes for the second time, filter, merging filtrate, it is 1.17 that filtrate is concentrated into 60 ℃ of surveys of relative density, adds ethanol, makes to contain the alcohol amount and reach 65%~70%, cold preservation 48 hours, filter, reclaim ethanol, add 0.5% active carbon, heated 30 minutes, filter, filtrate is concentrated into and is determined as 1.25~1.30 thick paste under 60 ℃ of the relative densities, drying under reduced pressure, be ground into fine powder, get heat-clearing and toxic substances removing extract powder 1455g.
(2) the equal 80 ℃ of oven dry of used adjuvant in the prescription, sieving for standby; With recipe quantity heat-clearing and toxic substances removing extractum fine powder 1455g and tartaric acid 1455g, sodium bicarbonate 1455g, stevioside 67.5g, xylitol 36g mixing, with dehydrated alcohol granulate, drying, add PEG6000 31.5g mixing, be pressed into 1000, promptly.