CN1586532A - Liushen oral disintegration tablet and its preparing method - Google Patents
Liushen oral disintegration tablet and its preparing method Download PDFInfo
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- CN1586532A CN1586532A CN 200410062452 CN200410062452A CN1586532A CN 1586532 A CN1586532 A CN 1586532A CN 200410062452 CN200410062452 CN 200410062452 CN 200410062452 A CN200410062452 A CN 200410062452A CN 1586532 A CN1586532 A CN 1586532A
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Abstract
The Liushen oral disintegrated tablet consists of cyclodextrin clathrate of six kinds of Chinese medicinal materials including bezoar, pearl, realgar, toad cake, musk and borneol and medicinal supplementary material. The preparation process is also disclosed. One kind of composite disintegrating agent is also disclosed, which consists of erythritol in 30-70 wt% and chitin or available common disintegrating agent. Compared with available technology, the present invention has shorter disintegration time, higher bioavailability, more powerful pharmacological effect and higher stability.
Description
Technical field
The invention belongs to technical field of Chinese medicines, be specifically related to a kind of LIUSHEN KOUQIANG BENGJIEPIAN and preparation method thereof.
Technical background
With Calculus Bovis, Margarita, Moschus, Borneolum Syntheticum, Venenum Bufonis, Realgar is the preparation that raw material is made, and has the effect of refreshing and detoxicating, anti-inflammatory analgetic, is mainly used in diseases such as scarlet fever, acute throat trouble, tonsillitis, laryngopharynx swelling and pain, carbuncle furuncle.Existing listing kind has LIUSHEN WAN (WS3-B-3374-98), and it is the little watered pill of above-mentioned raw materials medicine through being processed into, and disintegrate is slow, absorption is incomplete, low, the slow curative effect of bioavailability, mainly contains effects such as antiinflammatory, heart tonifying, detoxifcation, analgesia; Application number is 03131747 patent documentation, adopts LIUSHEN WAN by ear's acupuncture point pressing method is used for the treatment of hepatitis B.Venenum Bufonis has zest, and after the patient was oral, the oral cavity had pungent sensation, and therefore the crowd who is suitable for is restricted; Main effective ingredient muscone in Borneolum Syntheticum, the Moschus all has volatility, and permanent storage can make drug effect reduce.Application number is 01100171 patent documentation, adopts microwave extracting, concentrating under reduced pressure, supersonic jet technology to make nanometer six Miraculous drug medicines, and this explained hereafter cycle is long, the expense investment is big, is not suitable for very much for the medication preparation that contains above-mentioned raw materials.
In patent retrieval, find no any report that closes LIUSHEN KOUQIANG BENGJIEPIAN.
Oral cavity disintegration tablet is a kind of new pharmaceutical preparation, and it can absorb through hypoglossis mucous membrane, directly enters blood, has avoided first pass effect effectively, so taking dose is little, and safety is good, and effect rapidly.Though be oral formulations, can reach the effect of ejection preparation.Therefore just progressively become the focus that pharmaceutical manufacturer and research and development field are paid close attention to.This dosage form mainly is to select suitable fast disintegrant, by the existing certain rigidity of its tablet of making, certain sedimentation is arranged again.Can not need the water assisting deglutition when taking, can rapid disintegrate become fine grained in the oral cavity, only several swallowing acts can be finished drug administration process.Its more common solid orally ingestible absorbs fast, bioavailability height, and taking convenience.For the oral disease patient, LIUSHEN KOUQIANG BENGJIEPIAN of the present invention is especially suitable.
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, and it is fast to discharge medicine, reaches rapid-action effect, seeks suitable disintegrants, to guarantee oral cavity disintegration tablet disintegrate rapidly in the oral cavity; 2, seek relatively inexpensive pharmaceutic adjuvant, to reduce production cost; 3, 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.
Disintegrating agent is commonly used in the oral cavity disintegration tablet adjuvant have low-substituted hydroxypropyl cellulose (L-HPC), cross-linking sodium carboxymethyl cellulose (CCNa), crospolyvinylpyrrolidone (PVPP), crosslinked carboxymethylstach sodium (CCMS-Na) etc. [He Jianchang, etc.New oral solid quick releasing formulation-oral cavity quick disintegrating slice.The pharmacy practice magazine, 2000,18 (3): 151].These adjuvants are all water insoluble, but a common characteristic is all arranged, and have hygroscopicity [pharmaceutical preparation portion of Shanghai Institute of Pharmaceutical Industry, Pharmaceutical National Engineering Research Center exactly.Pharmaceutic adjuvant application technology (second edition), Chinese Medicine science and technology publishing house, 2002,73～75].In the higher environment of humidity, oral cavity disintegration tablet is the moisture absorption especially easily, and cracked trend is arranged.So relatively harsher to environment requirement in production, storage and transportation with the oral cavity disintegration tablet that these adjuvants are made, must adopt special packing, seal cover, desiccant bag etc., all can produce considerable influence to production cost.And above-mentioned disintegrating agent all is synthetic through chemical process, and price is higher, for the more relatively oral cavity disintegration tablet of adjuvant content, can cause production cost to increase, and and then can increase patient's financial burden.Therefore, seek disintegrating agent functional, that price is suitable, make that the disintegration time of oral cavity disintegration tablet is shorter, price is more cheap, stability better becomes one of key problem in technology of exploitation oral cavity disintegration tablet.
Application number is 99802175 patent application bibliographical information, and during as disintegrating agent, the hardness of making oral cavity disintegration tablet is identical with disintegration time at the erythritol that uses separately equivalent or low-substituted hydroxypropyl cellulose (L-HPC).The erythritol sweet taste is pure, after eating nice and cool mouthfeel characteristic is arranged, and also can make correctives and use, and reduces the weight of oral cavity disintegration tablet.Erythritol can not influence normal carbohydrate metabolism, is fit to diabetes patient; And be sweet taste material low in calories, be suitable for obese patients, simultaneously caries prevention is also had positive role.
Chitin is the relatively low natural pharmaceutic adjuvant of a kind of price, and it has another name called chitin, chitin, is a kind of biological polysaccharide polymer material, extensively is present in the carapace in the unicellular lower eukaryote.This material can be degraded by lyase, has good biocompatibility, avirulence, chemical property quite stable.
Summary of the invention
The objective of the invention is in order to overcome the deficiency that above-mentioned prior art exists, the LIUSHEN KOUQIANG BENGJIEPIAN preparation that a kind of taking convenience, mouthfeel are good, rapid-action to indication, reach obvious, preparation stabilization of peak morning, bioavailability height, curative effect is provided.
Another object of the present invention provides the preparation method of LIUSHEN KOUQIANG BENGJIEPIAN.
In the selection course that disintegrating agent uses in oral cavity disintegration tablet, we discover that erythritol and disintegrating agent commonly used at present mix by a certain percentage, form a kind of compound disintegrating agent and have more performance, the oral cavity disintegration tablet made from it compares with the simple oral cavity disintegration tablet that uses erythritol or disintegrating agent commonly used at present to make, the disintegration time of oral cavity disintegration tablet was shortened, and because erythritol has very little hygroscopicity, the stability of the feasible oral cavity disintegration tablet of making significantly improves.In the compound disintegrating agent, erythritol is in the amount ranges of 30%-70%, and along with the increase of content, the disintegration time of oral cavity disintegration tablet shortens, and stability strengthens.
We find that in experiment chitin disintegrating agent effect with commonly used at present aspect the disintegrate effect is suitable, even are better than disintegrating agent commonly used.
We have studied compound disintegrating agent in experiment, select the mixture of use erythritol and chitin, disintegrating agent commonly used, are based on many-sided consideration.When making disintegrating agent with single erythritol, though erythritol has very little hygroscopicity, the tablet stability of making is good, and the swelling degree after the single erythritol suction is less, influences the disintegrating property of oral cavity disintegration tablet, and disintegration time is prolonged.Add a certain amount of disintegrating agent commonly used, utilize rapid expansible character after their moisture absorptions, neither influence the stability of oral cavity disintegration tablet, also kept the characteristic of its rapid disintegrate, reached reasonable effect.
The present invention is achieved through the following technical solutions:
One, process recipes
(1) the crude drug weight proportion is: Calculus Bovis 3-4.5 part, Margarita 3-4.5 part, Realgar 2-3 part, Moschus 3-4.5 part, Borneolum Syntheticum 2-3 part, Venenum Bufonis 2-3 part;
(2) Calculus Bovis, Margarita, Realgar are ground into impalpable powder respectively, mixing gets medicated powder;
(3) Venenum Bufonis, Moschus are pulverized, and put into the supersound extraction jar, the ethanol of the 50%-85% that adding 4-8 doubly measures, and supersound extract 2-4 time, time 30-60 minute, frequency of oscillation 30-80kHz, the control temperature is a room temperature; Merge extractive liquid, filters, and filtrate is concentrating under reduced pressure below 50 ℃; Borneolum Syntheticum joins in the above-mentioned concentrated solution with the small amount of ethanol dissolving; Concentrated solution is slowly joined in β-CD or the HP-β-CD saturated aqueous solution, and 50 ℃ were stirred 3 hours, continued under the room temperature to stir 5 hours, and cold preservation is spent the night, and filters, and obtains clathrate;
(4) preparation prescription proportioning of the present invention is: medicated powder 8-12 weight portion, clathrate 20-60 weight portion, disintegrating agent 30-90 weight portion, filler 105-245 weight portion, correctives 0-20 weight portion, lubricant 1-10 weight portion;
(5) above-mentioned medicated powder, clathrate are mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain oral cavity disintegration tablet.
Borneolum Syntheticum, Moschus, Venenum Bufonis are carried out enclose with cyclodextrin, reduced the volatility of Borneolum Syntheticum, the stability of volatile effective ingredient muscone increases in the Moschus, and the zest of Venenum Bufonis reduces, toxicity reduces; Being equipped with compound disintegrating agent of the present invention further increases stability of drug, improves the curative effect of medicine.
Two, the research of compound disintegrating agent
1. the disintegrating agent performance is investigated experiment
Experimental raw: erythritol, chitin, low-substituted hydroxypropyl methylcellulose, carboxymethyl starch sodium, crosslinked carboxymethyl fecula sodium, insoluble crospolyvinylpyrrolidone, buy by market.
Experimental technique:
(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 disintegrating agent, dry weighs fully, is put into 1 week under 25 ℃ and 75% the damp condition, takes by weighing weight, and the calculating wettability the results are shown in 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 disintegrating agent, and see Table 1.
Table 1 disintegrating agent performance is investigated relatively
Dissolubility W/V viscosity mpa.s wettability volume increases
Disintegrating agent
(37℃) (37℃) (％) (％)
Erythritol 45 3.5 0.03 0.02
Chitin--11.29 16.57
Low-substituted hydroxypropyl methylcellulose--14.09 20.36
Carboxymethyl starch sodium--21.07 22.89
Crosslinked carboxymethyl fecula sodium--22.18 28.14
Insoluble crospolyvinylpyrrolidone--22.64 27.62
Conclusion: the characteristics of investigating experiment and oral cavity disintegration tablet by above-mentioned performance, we can analyze, erythritol has very big advantage as disintegrating agent in wettability, but because its moisture pick-up properties is very little, volume increase degree is also very little, therefore, in disintegrating procedue volumetric expansion slow, can not reach the requirement of the rapid disintegrate of oral cavity disintegration tablet; Erythritol is again good correctives simultaneously, not only can be used as disintegrating agent but also can be used as correctives if choose suitable weight, can significantly reduce consumption, the operation in the formulation preparation process and the cost of preparation of pharmaceutic adjuvant; Other disintegrating agent hygroscopicity is too big, causes the Orally disintegrating tablet stability very poor; By analyzing, erythritol is carried out mixing of proper proportion with other disintegrating agent, the compound disintegrating agent as oral cavity disintegration tablet has good advantages.
2. the selection of compound disintegrating agent
Experimental raw: choose crosslinked carboxymethyl fecula sodium and carry out different proportion with erythritol and mix, mixed proportion is respectively erythritol: crosslinked carboxymethyl fecula sodium=1: 9 or 2: 8 or 3: 7 or 4: 6 or 5: 5 or 6: 4 or 7: 3 or 8: 2 or 9: 1, totally 9 groups, be respectively experimental group 1-9, with experimental group 1-9 and same filler (in microcrystalline Cellulose, the nano micro crystal cellulose a kind of) and lubricant (in magnesium stearate, Pulvis Talci, the Stepanol MG a kind of), carry out tabletting; Change above-mentioned disintegrating agent into chitin,, be experimental group 10, carry out tabletting with same filler, mix lubricant with weight; Change above-mentioned disintegrating agent into weight crosslinked carboxymethyl fecula sodium, with same filler, mix lubricant, experimental group 11 carries out tabletting.
Experimental technique:
(1) hardness of mensuration tablet: utilize the tablet hardness tester 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 Chinese pharmacopoeia utilizes the disintegrate tester to measure, and 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.
The selection of table 2 experimental group disintegrating agent
The hardness spoilage disintegration time Orally disintegrating time
Experimental group grittiness taste
(kg) (％) (s) (s)
1 4.1 22.1 42.1 51.2 have bad
2 3.9 21.6 43.6 52.9 have generally
3 2.1 9.3 26.3 32.9 is seldom good
4 2.2 8.6 25.2 28.3 is seldom good
5 2.2 8.1 26.1 26.7 is seldom good
6 2.1 8.6 26.9 27.4 is seldom good
7 2.0 9.3 26.8 27.3 is seldom good
8 1.9 9.6 35.9 38.6 is seldom good
9 1.8 10.2 35.6 39.1 is seldom good
10 4.6 33.9 54.1 62.9 have much very poor
11 4.8 36.5 55.6 62.8 have much very poor
Change above-mentioned chitin, crosslinked carboxymethyl fecula sodium into low-substituted hydroxypropyl methylcellulose, crosslinked carboxymethyl fecula sodium, crosslinked insoluble polyvinylpyrrolidone, experimentize, the result of experimental result and table 2 is close.
Experimental result shows, erythritol is mixed with into the mixing disintegrating agent with other disintegrating agent, has good effect, simultaneously because erythritol has sweet taste, so can reduce or replace correctives to use, by experiment erythritol: the suitable ratio of other disintegrating agent be 3-7: 7-3.
3. preparation disintegration time mensuration
In order to prove absolutely that the employed compound disintegrating agent of LIUSHEN KOUQIANG BENGJIEPIAN of the present invention has disintegrate characteristics rapidly than single disintegrating agent, we have carried out following experiment: disintegrating agent is selected in the design by table 3 for use, make into oral cavity disintegration tablet with effective ingredient at identical pressure lower sheeting, place the beaker of the 10ml that fills 37 ℃ of water of 5ml, stir with 30 rev/mins speed, measure the disintegration of the oral cavity disintegration tablet that contains different disintegrating agents.
Table 3 preparation disintegration time mensuration
Disintegrating agent
Disintegration
The experiment consumption
Form (s)
(g∶g)
1 chitin-32.2
2 erythritols: chitin 3: 7 18.7
3 low-substituted hydroxypropyl methylcellulose-28.8
4 erythritols: low-substituted hydroxypropyl methylcellulose 4: 6 16.2
5 carboxymethyl starch sodium-37.6
6 erythritols: carboxymethyl starch sodium 5: 5 14.9
7 crosslinked carboxymethyl fecula sodium-41.4
8 erythritols: crosslinked carboxymethyl fecula sodium 6: 4 13.4
9 insoluble crospolyvinylpyrrolidone-34.1
10 erythritols: insoluble crospolyvinylpyrrolidone 7: 3 12.6
The result: the oral cavity disintegration tablet that uses compound disintegrating agent is in 12.6-18.7 all disintegrates and by No. 2 sieves in second: the oral cavity disintegration tablet that uses single disintegrating agent is in 28.8-41.4 all disintegrates and sieve by No. 2 in second.Illustrate that compound disintegrating agent of the present invention has disintegrate characteristics rapidly really.
Three, dissolution experiment
1. instrument and the full-automatic digestion instrument of reagent SR-6 type (U.S. Hanson company); Distilled water (self-control); LIUSHEN WAN (the fair pharmaceutical factory of going up of Suzhou thunder); LIUSHEN KOUQIANG BENGJIEPIAN (Qianluchun Science and Technology Co., Ltd., Beijing's laboratory provides).
2. experimental technique is pressed in the dissolution method (" two appendix XC of Chinese pharmacopoeia version in 2000) second method and is measured.Each container fills the distilled water through degassing processing of 100ml, and heating makes water temperature remain on 37 ℃ ± 0.5 ℃, and rotating speed of agitator is 50 rev/mins.Put into 1 of LIUSHEN KOUQIANG BENGJIEPIAN of the present invention, take out 2ml solution at regular intervals, centrifugal 10 minutes (12000rpm), supernatant are as need testing solution, with " content assaying method is measured cholic acid content under 52 pages of Calculus Bovis items of Chinese pharmacopoeia version in 2000.The results are shown in Table 4.
The dissolution experiment of table 4 six refreshing preparations
Sample time (min)
Medicine
0.5 1 2 4 8 15 20 40
LIUSHEN WAN 12.6 16.8 20.0 23.2 25.3 30.4 36.5 46.8
LIUSHEN KOUQIANG BENGJIEPIAN 32.3 36.6 39.8 43.1 45.2 47.3 48.4 48.4
Conclusion: LIUSHEN KOUQIANG BENGJIEPIAN 0.5min, dissolution rate can reach complete stripping in 67%, 20 minute.And LIUSHEN WAN 0.5min stripping is less than 27%.Therefore, LIUSHEN KOUQIANG BENGJIEPIAN of the present invention has produce effects characteristics rapidly.
Four, pharmacology embodiment
1. xylol causes the inhibitory action of mice ear
3 groups of 30 branches of mice, matched group, LIUSHEN WAN group, LIUSHEN KOUQIANG BENGJIEPIAN group, administration is continuous 7 days respectively, and 1h behind the 7th day medicine is coated with dimethylbenzene 25 μ l in the mouse right ear two sides, left side ear is not painted with normal ear, behind the 2h, take off cervical vertebra and put to death, the disk of laying left ear and the same position of auris dextra with diameter 8mm card punch, on torsion balance, weigh, calculate ear swelling rate and suppression ratio.The results are shown in Table 5.
Table 5 six refreshing preparation xylol cause the inhibitory action (X ± SD) of mice ear
Group Mus number (only) ear swelling rate (%) suppression ratio (%)
Matched group 10 125.86 ± 47.28-
LIUSHEN WAN group 10 79.46 ± 42.34
*36.87
LIUSHEN KOUQIANG BENGJIEPIAN group 10 67.88 ± 39.72
*# 46.07
Annotate: compare with matched group:
*P＜0.01;
Compare with the LIUSHEN WAN group: #P＜0.05.
LIUSHEN KOUQIANG BENGJIEPIAN, LIUSHEN WAN xylol cause mice ear inhibitory action (P＜0.01); LIUSHEN KOUQIANG BENGJIEPIAN is compared with LIUSHEN WAN, suppression ratio also variant (P＜0.05).Illustrate: the pharmacological action of LIUSHEN KOUQIANG BENGJIEPIAN is better than LIUSHEN WAN.
2. writhing method analgesic test
3 groups of 30 branches of mice, matched group, LIUSHEN WAN group, LIUSHEN KOUQIANG BENGJIEPIAN group, continuous 7 days of each group difference administration; 1h after the last administration, lumbar injection 0.8% acetic acid 0.2ml/ only turn round the body number of times in record 5～20min.The results are shown in Table 6.
The influence that table 6 six refreshing preparations react mouse writhing (X ± SD)
Group Mus number (only) is turned round body number of times (n) suppression ratio (%)
Matched group 10 34.87 ± 13.57-
LIUSHEN WAN group 10 18.24 ± 16.62
*47.69
LIUSHEN KOUQIANG BENGJIEPIAN group 10 13.85 ± 11.39
*# 60.28
Annotate: compare with matched group:
*P＜0.01;
Compare with the LIUSHEN WAN group: #P＜0.05
LIUSHEN KOUQIANG BENGJIEPIAN, LIUSHEN WAN all can significantly reduce mouse writhing number of times (P＜0.01); LIUSHEN KOUQIANG BENGJIEPIAN is compared with LIUSHEN WAN, turns round body number of times also variant (P＜0.05).Illustrate: the pharmacological action of LIUSHEN KOUQIANG BENGJIEPIAN is better than LIUSHEN WAN.
3. hot-plate analgesic test
Water temperature is constant in 55 ± 0.5 ℃, gets 30 of the qualified mices of preliminary election, divides 3 groups at random.Matched group, LIUSHEN WAN group and LIUSHEN KOUQIANG BENGJIEPIAN group.Each group difference successive administration 7 days, 1h measures the pain threshold of each mice after the last administration.The results are shown in Table 7.
Table 7 six refreshing preparation xylol cause the inhibitory action (X ± SD) of mice ear
Mus is counted pain threshold (s)
Group
After the preceding administration of (only) administration
Matched group 10 18.83 ± 3.83 18.27 ± 5.86
LIUSHEN WAN group 10 18.47 ± 3.74 25.48 ± 6.17
*
LIUSHEN KOUQIANG BENGJIEPIAN group 10 19.04 ± 4.26 28.14 ± 5.35
*#
Annotate: compare with matched group:
*P＜0.01;
Compare with the LIUSHEN WAN group: #P＜0.05.
LIUSHEN KOUQIANG BENGJIEPIAN, LIUSHEN WAN all can significantly increase the pain threshold (P＜0.01) of mice; LIUSHEN KOUQIANG BENGJIEPIAN is compared with LIUSHEN WAN, and pain threshold improves also variant (P＜0.05).Illustrate: the pharmacological action of LIUSHEN KOUQIANG BENGJIEPIAN is better than LIUSHEN WAN.
Above pharmacological evaluation proves to have better therapeutic effect with LIUSHEN KOUQIANG BENGJIEPIAN.
Five, preparation embodiment
Embodiment 1
(1) crude drug weight is: Calculus Bovis 4.5g, Margarita 4.5g, Realgar 3g, Moschus 4.5g, Borneolum Syntheticum 3g, Venenum Bufonis 3g;
(2) Calculus Bovis, Margarita, Realgar are ground into impalpable powder respectively, mixing gets medicated powder;
(3) Venenum Bufonis, Moschus are pulverized, and put into the supersound extraction jar, add 85% ethanol of 8 times of amounts, supersound extract 4 times, and each 60 minutes time, frequency of oscillation 80kHz, the control temperature is a room temperature; Merge extractive liquid, filters, and filtrate is concentrating under reduced pressure below 50 ℃; Borneolum Syntheticum joins in the above-mentioned concentrated solution with the small amount of ethanol dissolving; Concentrated solution is slowly joined in HP-β-CD saturated aqueous solution, and 50 ℃ were stirred 3 hours, continued under the room temperature to stir 5 hours, and cold preservation is spent the night, and filters, and obtains clathrate 60g;
(4) preparation prescription is:
Medicated powder 12g
Clathrate 60g
Nano micro crystal cellulose 105g
Erythritol 39g
Chitin 51g
Mannitol 20g
Magnesium stearate 10g
(5) medicated powder, clathrate are mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain 1000 of oral cavity disintegration tablets.
Embodiment 2
(1) crude drug weight is: Calculus Bovis 3g, Margarita 3g, Realgar 2g, Moschus 3g, Borneolum Syntheticum 2g, Venenum Bufonis 2g;
(2) Calculus Bovis, Margarita, Realgar are ground into impalpable powder respectively, mixing gets medicated powder;
(3) Venenum Bufonis, Moschus are pulverized, and put into the supersound extraction jar, add 50% ethanol of 4 times of amounts, supersound extract 2 times, and each 40 minutes time, frequency of oscillation 55kHz, the control temperature is a room temperature; Merge extractive liquid, filters, and filtrate is concentrating under reduced pressure below 50 ℃; Borneolum Syntheticum joins in the above-mentioned concentrated solution with the small amount of ethanol dissolving; Concentrated solution is slowly joined in β-CD saturated aqueous solution, and 50 ℃ were stirred 3 hours, continued under the room temperature to stir 5 hours, and cold preservation is spent the night, and filters, and obtains clathrate 20g;
(4) preparation prescription is:
Medicated powder 8g
Clathrate 20g
Microcrystalline Cellulose 245g
Erythritol 21g
Carboxymethyl starch sodium 9g
Pulvis Talci 1g
(5) medicated powder, clathrate are mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain 1000 of oral cavity disintegration tablets.
Embodiment 3
(1) crude drug weight is: Calculus Bovis 3.5g, Margarita 3.5g, Realgar 2.5g, Moschus 3.5g, Borneolum Syntheticum 2.5g, Venenum Bufonis 2.5g;
(2) Calculus Bovis, Margarita, Realgar are ground into impalpable powder respectively, mixing gets medicated powder;
(3) Venenum Bufonis, Moschus are pulverized, and put into the supersound extraction jar, add 70% ethanol of 6 times of amounts, supersound extract 3 times, and 50 minutes time, frequency of oscillation 40kHz, the control temperature is a room temperature; Merge extractive liquid, filters, and filtrate is concentrating under reduced pressure below 50 ℃; Borneolum Syntheticum joins in the above-mentioned concentrated solution with the small amount of ethanol dissolving; Concentrated solution is slowly joined in HP-β-CD saturated aqueous solution, and 50 ℃ were stirred 3 hours, continued under the room temperature to stir 5 hours, and cold preservation is spent the night, and filters, and obtains clathrate 47g;
(4) preparation prescription is:
Medicated powder 9.5g
Clathrate 47g
Nano micro crystal cellulose 182g
Erythritol 16g
Crosslinked carboxymethyl fecula sodium 37g
Stevioside 1.5g
Stepanol MG 7g
(5) medicated powder, clathrate are mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain 1000 of oral cavity disintegration tablets.
Embodiment 4
(1) crude drug weight is: Calculus Bovis 4.0g, Margarita 4.0g, Realgar 2.7g, Moschus 4.0g, Borneolum Syntheticum 2.3g, Venenum Bufonis 2.8g;
(2) Calculus Bovis, Margarita, Realgar are ground into impalpable powder respectively, mixing gets medicated powder;
(3) Venenum Bufonis, Moschus are pulverized, and put into the supersound extraction jar, add 60% ethanol of 5 times of amounts, supersound extract 3 times, and 30 minutes time, frequency of oscillation 30kHz, the control temperature is a room temperature; Merge extractive liquid, filters, and filtrate is concentrating under reduced pressure below 50 ℃; Borneolum Syntheticum joins in the above-mentioned concentrated solution with the small amount of ethanol dissolving; Concentrated solution is slowly joined in β-CD saturated aqueous solution, and 50 ℃ were stirred 3 hours, continued under the room temperature to stir 5 hours, and cold preservation is spent the night, and filters, and obtains clathrate 38g;
(4) preparation prescription is:
Medicated powder 10.7g
Clathrate 38g
Microcrystalline Cellulose 174g
Erythritol 44g
Crospolyvinylpyrrolidone 23g
Mannitol 5.3g
Magnesium stearate 5g
(5) medicated powder, clathrate are mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain 1000 of oral cavity disintegration tablets.
Embodiment 5
(1) crude drug weight is: Calculus Bovis 3.7g, Margarita 4.2g, Realgar 2.2g, Moschus 3.8g, Borneolum Syntheticum 2.8g, Venenum Bufonis 2.3g;
(2) Calculus Bovis, Margarita, Realgar are ground into impalpable powder respectively, mixing gets medicated powder;
(3) Venenum Bufonis, Moschus are pulverized, and put into the supersound extraction jar, add 75% ethanol of 7 times of amounts, supersound extract 4 times, and 45 minutes time, frequency of oscillation 60kHz, the control temperature is a room temperature; Merge extractive liquid, filters, and filtrate is concentrating under reduced pressure below 50 ℃; Borneolum Syntheticum joins in the above-mentioned concentrated solution with the small amount of ethanol dissolving; Concentrated solution is slowly joined in HP-β-CD saturated aqueous solution, and 50 ℃ were stirred 3 hours, continued under the room temperature to stir 5 hours, and cold preservation is spent the night, and filters, and obtains clathrate 26g;
(4) preparation prescription is:
Medicated powder 10.1g
Clathrate 26g
Nano micro crystal cellulose 171g
Erythritol 30g
Low-substituted hydroxypropyl methylcellulose 44g
Stevioside 16g
Magnesium stearate 3g
(5) medicated powder, clathrate are mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain 1000 of oral cavity disintegration tablets.
1 of the every clothes of adult of the present invention, 3 times on the one.
Claims (6)
1. LIUSHEN KOUQIANG BENGJIEPIAN is characterized in that it is a medicated powder 8-12 weight portion by Calculus Bovis, Margarita, Realgar, and the cyclodextrin clathrate 20-60 weight portion of Venenum Bufonis, Moschus, Borneolum Syntheticum and pharmaceutic adjuvant are formed; Its feature also is disintegrating agent 30-90 weight portion in the pharmaceutic adjuvant, filler 105-245 weight portion, correctives 0-20 weight portion, lubricant 1-10 weight portion.
2. disintegrating agent according to claim 1 is by erythritol and a kind of compound disintegrating agent of forming that is selected from chitin, low-substituted hydroxypropyl methylcellulose, carboxymethyl starch sodium, crosslinked carboxymethyl fecula sodium, the insoluble crospolyvinylpyrrolidone, and the weight percentage of its mesoerythrit is 30%-70%.
3. oral cavity disintegration tablet according to claim 1, its preparation method may further comprise the steps:
(1) the crude drug weight proportion is: Calculus Bovis 3-4.5 part, Margarita 3-4.5 part, Realgar 2-3 part, Moschus 3-4.5 part, Borneolum Syntheticum 2-3 part, Venenum Bufonis 2-3 part;
(2) Calculus Bovis, Margarita, Realgar are ground into impalpable powder respectively, mixing gets medicated powder;
(3) Venenum Bufonis, Moschus are pulverized, and put into the supersound extraction jar, the ethanol of the 50%-85% that adding 4-8 doubly measures, and supersound extract 2-4 time, time 30-60 minute, frequency of oscillation 30-80kHz, the control temperature is a room temperature; Merge extractive liquid, filters, and filtrate is concentrating under reduced pressure below 50 ℃; Borneolum Syntheticum joins in the above-mentioned concentrated solution with the small amount of ethanol dissolving; Concentrated solution is slowly joined in β-CD or the HP-β-CD saturated aqueous solution, and 50 ℃ were stirred 3 hours, continued under the room temperature to stir 5 hours, and cold preservation is spent the night, and filters, and obtains clathrate;
(4) medicated powder, clathrate are mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain oral cavity disintegration tablet.
4. be a kind of in microcrystalline Cellulose or the nano micro crystal cellulose according to claim 1 or 3 described filleies.
5. be a kind of in mannitol or the stevioside according to claim 1 or 3 described correctivess.
6. be a kind of in magnesium stearate or Pulvis Talci or the Stepanol MG according to claim 1 or 3 described lubricants.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410062452 CN1586532A (en) | 2004-07-09 | 2004-07-09 | Liushen oral disintegration tablet and its preparing method |
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200410062452 CN1586532A (en) | 2004-07-09 | 2004-07-09 | Liushen oral disintegration tablet and its preparing method |
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| CN1586532A true CN1586532A (en) | 2005-03-02 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100415248C (en) * | 2005-06-16 | 2008-09-03 | 江西本草天工科技有限责任公司 | Masa Medicata Fermentate health-care prepn., and its prepn. method |
-
2004
- 2004-07-09 CN CN 200410062452 patent/CN1586532A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100415248C (en) * | 2005-06-16 | 2008-09-03 | 江西本草天工科技有限责任公司 | Masa Medicata Fermentate health-care prepn., and its prepn. method |
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