CN1293895C - Oral disintegration tablet for laryngopathy and its preparing method - Google Patents
Oral disintegration tablet for laryngopathy and its preparing method Download PDFInfo
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- CN1293895C CN1293895C CNB200410062450XA CN200410062450A CN1293895C CN 1293895 C CN1293895 C CN 1293895C CN B200410062450X A CNB200410062450X A CN B200410062450XA CN 200410062450 A CN200410062450 A CN 200410062450A CN 1293895 C CN1293895 C CN 1293895C
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- disintegration tablet
- oral cavity
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- disintegrating agent
- cavity disintegration
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- 239000003795 chemical substances by application Substances 0.000 claims abstract description 50
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- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
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Abstract
The present invention discloses an orally disintegrating tablet for treating laryngopathy and a preparation method thereof. The orally disintegrating tablet for treating laryngopathy is prepared from the extract of isatis root, natural indigo and pig's bile, the powder of bezoar, exsiccated sodium sulfate, realgar, borax and plant soot, cyclodextrin inclusion compound of toad venom and borneol, and pharmaceutical adjuvant. The present invention also discloses a composite disintegrating agent for preparing orally disintegrating tablets, which is prepared from 30 to 70 wt% of erythritol and chitin or current frequently-used disintegrating agent. Experimental results show that: compared with the existing preparation, the orally disintegrating tablet prepared by the preparation method of the present invention has the advantages of shorter disintegration time, higher biological availability and stronger pharmacological action.
Description
Technical field
The invention belongs to technical field of Chinese medicines, be specifically related to a kind of oral disintegration tablet for laryngopathy and preparation method thereof.
Technical background
Throat is one of human body vitals, is the organ of swallowing food, breathe air, pronunciation, and the pharyngolaryngitis patient who suffers from various degree accounts for 40% among the crowd, has a strong impact on people's life, study, work.Present western medicine is disease controlling temporarily, takes too many antibiotic medicine, and antibiotic or sulfonamides can cause human body negative and positive disequilibrium, immunologic hypofunction, and resistance goes down, and causes the state of an illness difficult repeatedly.And Chinese patent medicine has unique curative effect to various pharyngolaryngitis.With Radix Isatidis, Calculus Bovis, Borneolum Syntheticum, Fel Sus domestica, Matrii Sulfas Exsiccatus, Indigo Naturalis, Realgar, Borax, Venenum Bufonis (processed with wine), Pulvis Fumi Carbonisatus is the preparation that raw material is made, and has the effect of heat-clearing and toxic substances removing, reducing swelling and alleviating pain, is used for pharyngitis, laryngitis, tonsillitis and general furuncle.Radix Isatidis, the fire-toxin of the high Sheng of stomach that can clear away heart-fire can be separated swelling and ache of throat, closes the effect that Calculus Bovis, Fel Sus domestica are played detoxifcation, heat clearing away, detumescence, pain relieving altogether.Realgar, Borneolum Syntheticum, Borax heat-clearing and toxic substances removing, the sore-throat relieving corruption, the Venenum Bufonis reducing swelling and alleviating pain, for separating the key medicine of throat toxic swelling, the Matrii Sulfas Exsiccatus detumescence of relieving inflammation or internal heat, purging heat to relax the bowels, Pulvis Fumi Carbonisatus, Indigo Naturalis clearing away heat and cooling blood.Existing listing kind has pills for throat disease (WS3-B-0845), 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; 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; Borneolum Syntheticum has volatility, and permanent storage can make drug effect reduce.Application number is 01100673 patent documentation, adopts microwave extracting, concentrating under reduced pressure, supersonic jet technology to make nano medicine for treating throat disease, 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 oral disintegration tablet for laryngopathy.
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, oral disintegration tablet for laryngopathy 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 one 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 excellent biological compatibility, 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 oral disintegration tablet for laryngopathy 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 oral disintegration tablet for laryngopathy.
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: Radix Isatidis 35-50 part, Calculus Bovis 2.5-3.5 part, Borneolum Syntheticum 1.2-1.6 part, Fel Sus domestica 34-46 part, Matrii Sulfas Exsiccatus 1.7-2.3 part, Indigo Naturalis 1.0-1.4 part, Realgar 4.0-5.0 part, Borax 1.7-2.3 part, Venenum Bufonis (processed with wine) 3.5-4.5 part, Pulvis Fumi Carbonisatus 1.3-1.9 part;
(2) Radix Isatidis, Indigo Naturalis pulverizing medicinal materials are doubly measured the 60%-90% ethanol extraction 2 times with 6-10, and each 1 hour, merge extractive liquid, filtered, and filtrate decompression concentrates, and merges with Fel Sus domestica filtrate, and drying is pulverized, and obtains extract;
(3) Calculus Bovis, Matrii Sulfas Exsiccatus, Realgar, Borax, Pulvis Fumi Carbonisatus are ground into impalpable powder respectively, mixing gets medicated powder;
(4) with Venenum Bufonis (processed with wine), put into the supersound extraction jar, the ethanol of the 50%-85% that adding 4-8 doubly measures, 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;
(5) preparation prescription proportioning of the present invention is: extract 5-15 weight portion, medicated powder 11.2-15 weight portion, clathrate 8-30 weight portion, disintegrating agent 30-90 weight portion, filler 120-245 weight portion, correctives 0-20 weight portion, lubricant 1-10 weight portion;
(6) said extracted thing, medicated powder, clathrate are mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain oral cavity disintegration tablet.
Radix Isatidis, Indigo Naturalis medical material are extracted, remove impurity, the effective ingredient that enrichment is wherein contained has reduced dose, has improved bioavailability; Extract and Borneolum Syntheticum to Venenum Bufonis (processed with wine) carry out enclose with cyclodextrin, have reduced the volatility of Borneolum Syntheticum, and the zest of Venenum Bufonis reduces, toxicity reduces; Using compound disintegrating agent of the present invention further increases stability of drug, improves curative effect.
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
| Disintegrating agent | Dissolubility W/V (37 ℃) | Viscosity mpa.s (37 ℃) | Wettability (%) | Volume increases (%) |
| Erythritol chitin low-substituted hydroxypropyl methylcellulose | 45 - - | 3.5 - - | 0.03 11.29 14.09 | 0.02 16.57 20.36 |
| The insoluble crospolyvinylpyrrolidone of carboxymethyl starch sodium crosslinked carboxymethyl fecula sodium | - - - | - - - | 21.07 22.18 22.64 | 22.89 28.14 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
| Experimental group | Hardness (kg) | Spoilage (%) | Disintegration time (s) | The Orally disintegrating time (s) | Grittiness | Taste |
| 1 2 3 4 5 6 7 8 9 10 11 | 4.1 3.9 2.1 2.2 2.2 2.1 2.0 1.9 1.8 4.6 4.8 | 22.1 21.6 9.3. 8.6 8.1 8.6 9.3 9.6 10.2 33.9 36.5 | 42.1 43.6 26.3 25.2 26.1 26.9 26.8 35.9 35.6 54.1 55.6 | 51.2 52.9 32.9 28.3 26.7 27.4 27.3 38.6 39.1 62.9 62.8 | Having seldom to have much has a lot | Bad generally carefully good carefully 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 oral disintegration tablet for laryngopathy 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
| The experiment number | Disintegrating agent | Disintegration |
| Form | Consumption (g: g) | (s) | |
| 1 2 3 4 5 6 7 8 9 10 | Chitin antierythrite: chitin low-substituted hydroxypropyl methylcellulose antierythrite: low-substituted hydroxypropyl methylcellulose sodium carboxymethyl starch antierythrite: sodium carboxymethyl starch crosslinked carboxymethyl fecula sodium antierythrite: the insoluble PVPP antierythrite of crosslinked carboxymethyl fecula sodium: insoluble PVPP | - 3∶7 - 4∶6 - 5∶5 - 6∶4 - 7∶3 | 32.2 19.5 28.2 16.2 37.6 14.9 43.6 13.4 34.1 12.8 |
The result: the oral cavity disintegration tablet that uses compound disintegrating agent is in 12.8-19.5 all disintegrates and by No. 2 sieves in second; The oral cavity disintegration tablet that uses single disintegrating agent is in 28.2-43.6 all disintegrates and by No. 2 sieves 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); Pills for throat disease (the fair pharmaceutical factory of going up of Suzhou thunder); Oral disintegration tablet for laryngopathy (Qianluchun Science and Technology Co., Ltd., Beijing's laboratory provides).
2. experimental technique is pressed in the dissolution method (" two appendix X of Chinese pharmacopoeia version in 2000 C) 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 oral disintegration tablet for laryngopathy 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 larynx disease preparation
| Medicine | Sample time (min) | |||||||
| 0.5 | 1 | 2 | 4 | 8 | 15 | 20 | 40 | |
| The pills for throat disease oral disintegration tablet for laryngopathy | 13.6 23.7 | 17.8 26.6 | 20.0 29.8 | 23.2 31.1 | 25.3 33.2 | 30.4 35.3 | 36.5 37.2 | 36.8 37.2 |
Conclusion: oral disintegration tablet for laryngopathy 0.5min, dissolution rate can reach complete stripping in 63%, 20 minute.And pills for throat disease 0.5min stripping is less than 37%.Therefore, oral disintegration tablet for laryngopathy 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, pills for throat disease group, oral disintegration tablet for laryngopathy 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 larynx disease preparation xylol causes the inhibitory action (X ± SD) of mice ear
| Group | Mus number (only) | Ear swelling rate (%) | Suppression ratio (%) |
| Matched group pills for throat disease group oral disintegration tablet for laryngopathy group | 10 10 10 | 124.68±46.59 78.35±44.46 * 66.88±41.83 *# | - 37.16 46.36 |
Annotate: compare with matched group:
*P＜0.01;
Compare with the pills for throat disease group: #P＜0.05.
Oral disintegration tablet for laryngopathy, pills for throat disease xylol cause mice ear inhibitory action (P＜0.01); Oral disintegration tablet for laryngopathy is compared with pills for throat disease, suppression ratio also variant (P＜0.05).Illustrate: the pharmacological action of oral disintegration tablet for laryngopathy is better than pills for throat disease.
2. writhing method analgesic test
3 groups of 30 branches of mice, matched group, pills for throat disease group, oral disintegration tablet for laryngopathy 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 larynx disease preparation reacts mouse writhing (X ± SD)
| Group | Mus number (only) | Turn round body number of times (n) | Suppression ratio (%) |
| Matched group pills for throat disease group oral disintegration tablet for laryngopathy group | 10 10 10 | 37.25±15.61 20.47±14.25 * 15.76±12.88 *# | - 45.05 57.69 |
Annotate: compare with matched group:
*P＜0.01;
Compare with the pills for throat disease group: #P＜0.05
Oral disintegration tablet for laryngopathy, pills for throat disease all can significantly reduce mouse writhing number of times (P＜0.01); Oral disintegration tablet for laryngopathy is compared with pills for throat disease, turns round body number of times also variant (P＜0.05).Illustrate: the pharmacological action of oral disintegration tablet for laryngopathy is better than pills for throat disease.
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, pills for throat disease group and oral disintegration tablet for laryngopathy 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 larynx disease preparation xylol causes the inhibitory action (X ± SD) of mice ear
| Group | Mus number (only) | Pain threshold (s) | |
| Before the administration | After the administration | ||
| Matched group pills for throat disease group oral disintegration tablet for laryngopathy group | 10 10 10 | 19.92±4.76 18.36±3.97 18.57±4.11 | 18.13±4.58 25.74±6.17 * 27.54±5.36 *# |
Annotate: compare with matched group:
*P＜0.01;
Compare with the pills for throat disease group: #P＜0.05.
Oral disintegration tablet for laryngopathy, pills for throat disease all can significantly increase the pain threshold (P＜0.01) of mice; Oral disintegration tablet for laryngopathy is compared with pills for throat disease, and pain threshold improves also variant (P＜0.05).Illustrate: the pharmacological action of oral disintegration tablet for laryngopathy is better than pills for throat disease.
Above pharmacological evaluation proves to have better therapeutic effect with oral disintegration tablet for laryngopathy.
Five, preparation embodiment
Embodiment 1
(1) crude drug weight is: Radix Isatidis 50g, Calculus Bovis 3.5g, Borneolum Syntheticum 1.6g, Fel Sus domestica 46g, Matrii Sulfas Exsiccatus 2.3g, Indigo Naturalis 1.4g, Realgar 5.0g, Borax 2.3g, Venenum Bufonis (processed with wine) 4.5g, Pulvis Fumi Carbonisatus 1.9g;
(2) Radix Isatidis, Indigo Naturalis pulverizing medicinal materials are doubly measured the 60%-90% ethanol extraction 2 times with 6-10, and each 1 hour, merge extractive liquid, filtered, and filtrate decompression concentrates, and merges with Fel Sus domestica filtrate, and drying is pulverized, and obtains extract 15.0g;
(3) Calculus Bovis, Matrii Sulfas Exsiccatus, Realgar, Borax, Pulvis Fumi Carbonisatus are ground into impalpable powder respectively, mixing gets medicated powder;
(4) Venenum Bufonis (processed with wine) is put into the supersound extraction jar, added 85% ethanol of 8 times of amounts, supersound extract 4 times, 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 30g;
(5) preparation prescription is:
Extract 15g
Medicated powder 15g
Clathrate 30g
Nano micro crystal cellulose 120g
Erythritol 39g
Chitin 51g
Mannitol 20g
Magnesium stearate 10g
(6) extract, medicated powder, clathrate are mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain 2000 of oral cavity disintegration tablets.
Embodiment 2
(1) crude drug weight is: Radix Isatidis 35g, Calculus Bovis 2.5g, Borneolum Syntheticum 1.2g, Fel Sus domestica 34g, Matrii Sulfas Exsiccatus 1.7g, Indigo Naturalis 1.0g, Realgar 4.0g, Borax 1.7g, Venenum Bufonis (processed with wine) 3.5g, Pulvis Fumi Carbonisatus 1.3g;
(2) Radix Isatidis, Indigo Naturalis pulverizing medicinal materials are doubly measured the 60%-90% ethanol extraction 2 times with 6-10, and each 1 hour, merge extractive liquid, filtered, and filtrate decompression concentrates, and merges with Fel Sus domestica filtrate, and drying is pulverized, and obtains extract 5g;
(3) Calculus Bovis, Matrii Sulfas Exsiccatus, Realgar, Borax, Pulvis Fumi Carbonisatus are ground into impalpable powder respectively, mixing gets medicated powder;
(4) Venenum Bufonis (processed with wine) is pulverized, put into the supersound extraction jar, add 50% ethanol of 4 times of amounts, supersound extract 2 times, 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 8g;
(5) preparation prescription is:
Extract 5g
Medicated powder 11.2g
Clathrate 8g
Microcrystalline Cellulose 245g
Erythritol 21g
Carboxymethyl starch sodium 9g
Pulvis Talci 1g
(6) extract, medicated powder, clathrate are mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain 2000 of oral cavity disintegration tablets.
Embodiment 3
(1) crude drug weight is: Radix Isatidis 42g, Calculus Bovis 3g, Borneolum Syntheticum 1.4g, Fel Sus domestica 40g, Matrii Sulfas Exsiccatus 2g, Indigo Naturalis 1.2g, Realgar 4.6g, Borax 2g, Venenum Bufonis (processed with wine) 4g, Pulvis Fumi Carbonisatus 1.6g;
(2) Radix Isatidis, Indigo Naturalis pulverizing medicinal materials are doubly measured the 60%-90% ethanol extraction 2 times with 6-10, and each 1 hour, merge extractive liquid, filtered, and filtrate decompression concentrates, and merges with Fel Sus domestica filtrate, and drying is pulverized, and obtains extract 7.5g;
(3) Calculus Bovis, Matrii Sulfas Exsiccatus, Realgar, Borax, Pulvis Fumi Carbonisatus are ground into impalpable powder respectively, mixing gets medicated powder;
(4) Venenum Bufonis (processed with wine) is put into the supersound extraction jar, added 70% ethanol of 6 times of amounts, supersound extract 3 times, 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 12.8g;
(5) preparation prescription is:
Extract 7.5g
Medicated powder 13.2g
Clathrate 12.8g
Nano micro crystal cellulose 205g
Erythritol 16g
Crosslinked carboxymethyl fecula sodium 37g
Stevioside 1.5g
Stepanol MG 7g
(6) extract, medicated powder, clathrate are mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain 2000 of oral cavity disintegration tablets.
Embodiment 4
(1) crude drug weight is: Radix Isatidis 40g, Calculus Bovis 3.2g, Borneolum Syntheticum 1.5g, Fel Sus domestica 43g, Matrii Sulfas Exsiccatus 1.9g, Indigo Naturalis 1.3g, Realgar 4.2g, Borax 2.2g, Venenum Bufonis (processed with wine) 3.7g, Pulvis Fumi Carbonisatus 1.7g;
(2) Radix Isatidis, Indigo Naturalis pulverizing medicinal materials are doubly measured the 60%-90% ethanol extraction 2 times with 6-10, and each 1 hour, merge extractive liquid, filtered, and filtrate decompression concentrates, and merges with Fel Sus domestica filtrate, and drying is pulverized, and obtains extract 13.6g;
(3) Calculus Bovis, Matrii Sulfas Exsiccatus, Realgar, Borax, Pulvis Fumi Carbonisatus are ground into impalpable powder respectively, mixing gets medicated powder;
(4) Venenum Bufonis (processed with wine) is pulverized, put into the supersound extraction jar, add 60% ethanol of 5 times of amounts, supersound extract 3 times, 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 24.7g;
(5) preparation prescription is:
Extract 13.6g
Medicated powder 13.2g
Clathrate 24.7g
Microcrystalline Cellulose 172g
Erythritol 44g
Crospolyvinylpyrrolidone 23g
Mannitol 5.3g
Magnesium stearate 5g
(6) extract, medicated powder, clathrate are mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain 2000 of oral cavity disintegration tablets.
Embodiment 5
(1) crude drug weight is: Radix Isatidis 45g, Calculus Bovis 2.8g, Borneolum Syntheticum 1.2g, Fel Sus domestica 38g, Matrii Sulfas Exsiccatus 2.2g, Indigo Naturalis 1.1g, Realgar 4.8g, Borax 1.8g, Venenum Bufonis (processed with wine) 4.2g, Pulvis Fumi Carbonisatus 1.4g;
(2) Radix Isatidis, Indigo Naturalis pulverizing medicinal materials are doubly measured the 60%-90% ethanol extraction 2 times with 6-10, and each 1 hour, merge extractive liquid, filtered, and filtrate decompression concentrates, and merges with Fel Sus domestica filtrate, and drying is pulverized, and obtains extract 10.2g;
(3) Calculus Bovis, Matrii Sulfas Exsiccatus, Realgar, Borax, Pulvis Fumi Carbonisatus are ground into impalpable powder respectively, mixing gets medicated powder;
(4) Venenum Bufonis (processed with wine) is pulverized, put into the supersound extraction jar, add 75% ethanol of 7 times of amounts, supersound extract 4 times, 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 18.6g;
(5) preparation prescription is:
Extract 10.2g
Medicated powder 13.0g
Clathrate 18.6g
Nano micro crystal cellulose 166g
Erythritol 30g
Low-substituted hydroxypropyl methylcellulose 44g
Stevioside 16g
Magnesium stearate 3g
(6) extract, medicated powder, clathrate are mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain 2000 of oral cavity disintegration tablets.
This
3 times on the bright one; 1～2 of the every clothes of adult.
Claims (7)
1. oral disintegration tablet for laryngopathy, its crude drug weight proportion is: Radix Isatidis 35-50 part, Calculus Bovis 2.5-3.5 part, Borneolum Syntheticum 1.2-1.6 part, Fel Sus domestica 34-46 part, Matrii Sulfas Exsiccatus 1.7-2.3 part, Indigo Naturalis 1.0-1.4 part, Realgar 4.0-5.0 part, Borax 1.7-2.3 part, Venenum Bufonis (processed with wine) 3.5-4.5 part, Pulvis Fumi Carbonisatus 1.3-1.9 part, it is characterized in that it is by Radix Isatidis, Indigo Naturalis, the extract 5-15 weight portion of Fel Sus domestica, Calculus Bovis, Matrii Sulfas Exsiccatus, Realgar, Borax, the medicated powder 11.2-15 weight portion of Pulvis Fumi Carbonisatus, Venenum Bufonis, the cyclodextrin clathrate 8-30 weight portion of Borneolum Syntheticum and pharmaceutic adjuvant are formed; Its feature also is disintegrating agent 30-90 weight portion in the pharmaceutic adjuvant, filler 120-245 weight portion, correctives 0-20 weight portion, lubricant 1-10 weight portion.
2. oral cavity disintegration tablet according to claim 1, disintegrating agent wherein 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) Radix Isatidis, Indigo Naturalis pulverizing medicinal materials are doubly measured the 60%-90% ethanol extraction 2 times with 6-10, and each 1 hour, merge extractive liquid, filtered, and filtrate decompression concentrates, and merges with Fel Sus domestica filtrate, and drying is pulverized, and obtains extract;
(2) Calculus Bovis, Matrii Sulfas Exsiccatus, Realgar, Borax, Pulvis Fumi Carbonisatus are ground into impalpable powder respectively, mixing gets medicated powder;
(3) with Venenum Bufonis (processed with wine), put into the supersound extraction jar, the ethanol of the 50%-85% that adding 4-8 doubly measures, 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) said extracted thing, medicated powder, clathrate are mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain oral cavity disintegration tablet.
4. oral cavity disintegration tablet according to claim 1, filler wherein are a kind of in microcrystalline Cellulose or the nano micro crystal cellulose.
5. oral cavity disintegration tablet according to claim 1, correctives wherein are a kind of in mannitol or the stevioside.
6. oral cavity disintegration tablet according to claim 1, lubricant wherein are a kind of in magnesium stearate or Pulvis Talci or the Stepanol MG.
7. oral cavity disintegration tablet according to claim 1, its crude drug weight proportion is: 42 parts of Radix Isatidis, 3 parts of Calculus Boviss, 1.4 parts of Borneolum Syntheticums, 40 parts of Fel Sus domestica, 2 parts of Matrii Sulfas Exsiccatus, 1.2 parts of Indigo Naturaliss, 4.6 parts of Realgars, 2 parts of Boraxs, 4 parts of Venenum Bufonis (processed with wine), 1.6 parts of Pulvis Fumi Carbonisatuss.
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| CNB200410062450XA CN1293895C (en) | 2004-07-09 | 2004-07-09 | Oral disintegration tablet for laryngopathy and its preparing method |
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| CNB200410062450XA CN1293895C (en) | 2004-07-09 | 2004-07-09 | Oral disintegration tablet for laryngopathy and its preparing method |
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| CN1293895C true CN1293895C (en) | 2007-01-10 |
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| CN110917288A (en) * | 2019-12-30 | 2020-03-27 | 常熟雷允上制药有限公司 | Inclusion preparation of traditional Chinese medicine composition with anti-tumor effect and preparation method and application thereof |
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