CN1313103C - Orally disintegrating tablet of bupleurum root and its preparation - Google Patents
Orally disintegrating tablet of bupleurum root and its preparation Download PDFInfo
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- CN1313103C CN1313103C CNB2004100498530A CN200410049853A CN1313103C CN 1313103 C CN1313103 C CN 1313103C CN B2004100498530 A CNB2004100498530 A CN B2004100498530A CN 200410049853 A CN200410049853 A CN 200410049853A CN 1313103 C CN1313103 C CN 1313103C
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- oral cavity
- cavity disintegration
- radix bupleuri
- disintegrating agent
- disintegration tablet
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- Medicinal Preparation (AREA)
Abstract
The present invention discloses a bupleurum root orally disintegrating tablet and a preparation method thereof. The bupleurum root orally disintegrating tablet is prepared from cyclodextrin inclusion compound of supercritical extract of medicinal bupleurum root, ethanol extract 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 higher content of effective component, shorter disintegration time, better stability and stronger pharmacological action.
Description
Technical field
The invention belongs to technical field of Chinese medicines, be specifically related to a kind of Radix Bupleuri oral cavity disintegration tablet and preparation method thereof.
Technical background
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.
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 excellent biological compatibility, avirulence, chemical property quite stable.
Radix Bupleuri is Umbelliferae Bupleurum plant, and tool induces sweat, brings down a fever, the dispersing the stagnated live-QI to relieve the stagnation of QI function, cures mainly cold, fever, alternate attack of chill and fever, diseases such as costa sternales stomachache.The main effective ingredient of Radix Bupleuri is volatile oil and saikoside; Volatile oil is the main effective ingredient of Radix Bupleuri antipyretic, and domestic many pharmacy producer extracts volatile oil with steam distillation always and makes injection of Radix Bupleuri.With traditional steam distillation production because: 1, the medical material soak time very little, the volatile ingredient stripping is not thorough; 2, part high boiling point volatile ingredient is difficult for steaming; 3, repeatedly distillation concentrate cause the part volatile ingredient destroyed [Li Ruilin, etc.Improve volatile ingredient extraction ratio measure in the Radix Bupleuri.Basic unit's Chinese medicine magazine, 2001,16 (4): 45].Thereby volatile oil concentration is low in the injection of Radix Bupleuri, and dosage is big.Saikoside has tangible antiinflammatory, analgesic, analgesic activity.For the extraction of saikoside because traditional handicraft temperature height, heated time are long, some saikoside content reduce or lose totally [Ge Fahuan, etc.Supercritical CO
2The research of extraction volatile oil and saponin thereof from Radix Bupleuri.CHINA JOURNAL OF CHINESE MATERIA MEDICA, 2000,25 (3): 149].
Radix Bupleuri oral liquid in " Chinese Pharmacopoeia) " version in 2000 adopts steam distillation to obtain volatile oil, and reuse water extraction saponin component is made oral liquid.This technology is very incomplete to the extraction of volatile oil, and saponin component is heated more than 6 hours, loss a lot [Zhang Ling, etc.The Radix Bupleuri Study on extraction.Chinese patent medicine, 1997,19 (8): 1].Radix Bupleuri antitussive sheet adopts the technology of water extract-alcohol precipitation to obtain precipitation as effective ingredient, and this can only obtain effective ingredient a very little part [Zhang Ling, etc.The heating extraction time is to the influence of saikoside A content.Chinese herbal medicine, 1997,28 (4): 212].In patent retrieval, find no report about the Radix Bupleuri oral cavity disintegration tablet.
Summary of the invention
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 objective of the invention is in order to overcome the deficiency that above-mentioned prior art exists, provide a kind of taking convenience, rapid-action to indication, reach the peak early, curative effect obviously, the Radix Bupleuri orally disintegrating tablet preparation of preparation stabilization.
The present invention is achieved through the following technical solutions:
One, process recipes
(1) raw medicinal material consists of: 100 weight portions;
(2) get the Radix Bupleuri pulverizing medicinal materials, cross the 20-60 mesh sieve, use supercritical extraction, extracting pressure is 10-50Mpa, at 20-70 ℃ of cycling extraction 1-4 hour, obtains the critical extract of super I; Supercritical extract is slowly added in β-CD or the HP-β-CD aqueous solution, and 50 ℃ were stirred 3 hours, continued under the room temperature to stir 5 hours, filtered, and obtained clathrate;
(3) with above-mentioned medicinal residues with twice of the ethanol extraction of 40%-85%; Be equivalent to medical material weight 6-10 solvent doubly each the adding; Extracted 2 hours for the first time, extracted 1 hour for the second time; Merge ethanol extract, filter, filtrate is concentrated into does not have the alcohol flavor; Last macroporous adsorbent resin, the washing of doubly measuring earlier with 3-6, reuse 50%-80% ethanol elution is collected ethanol elution; Concentrating under reduced pressure is concentrated into the extractum that relative density is 1.15-1.30 in the time of 50 ℃, drying obtains ethanol extraction;
(4) preparation prescription proportioning of the present invention is: clathrate 3-12 weight portion, extract 1.5-3 weight portion, disintegrating agent 4-10 weight portion, filler 10-20 weight portion, correctives 0.1-1 weight portion, lubricant 0.1-1 weight portion;
(5) clathrate, ethanol extraction are mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain oral cavity disintegration tablet.
Utilize the volatile ingredient in the supercritical fluid extraction Radix Bupleuri medical material, temperature is low, the time is short, extraction is complete, has kept original character of effective ingredient to greatest extent; Use cyclodextrin inclusion compound, and be equipped with the compound disintegrating agent that contains erythritol, further increase its stability; Ethanol extraction, the technology of macroporous adsorbent resin remove impurity has been removed impurity effectively, and saponin active ingredient has been played enrichment, has reduced dose.
Two, 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 (%) |
| The insoluble crospolyvinylpyrrolidone of erythritol chitin low-substituted hydroxypropyl methylcellulose carboxymethyl starch sodium crosslinked carboxymethyl fecula sodium | 45 - - - - - | 3.5 - - - - - | 0.03 11.29 14.09 21.07 22.18 22.64 | 0.02 16.57 20.36 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 are too big, cause oral cavity disintegration tablet very poor aspect stable; 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.
Three, 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 | 4.1 | 22.1 | 42.1 | 51.2 | Have | Bad |
| 2 3 4 5 6 7 8 9 10 11 | 3.9 2.1 2.2 2.2 2.1 2.0 1.9 1.8 4.6 4.8 | 21.6 9.3. 8.6 8.1 8.6 9.3 9.6 10.2 33.9 36.5 | 43.6 26.3 25.2 26.1 26.9 26.8 35.9 35.6 54.1 55.6 | 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 | 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.
Four, preparation disintegration time mensuration
In order to prove absolutely that the employed compound disintegrating agent of Radix Bupleuri oral cavity disintegration tablet 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
| Experimental group | Disintegrating agent | Disintegration (s) | |
| Form | Consumption (g: g) | ||
| 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 | 31.4 18.7 29.3 18.2 39.1 16.8 41.7 16.2 34.6 14.9 |
The result: the oral cavity disintegration tablet that uses compound disintegrating agent is in 14.9-18.7 all disintegrates and by No. 2 sieves in second; The oral cavity disintegration tablet that uses single disintegrating agent is in 29.3-41.7 all disintegrates and by No. 2 sieves in second.Illustrate that compound disintegrating agent of the present invention has disintegrate characteristics rapidly really.
Five, assay analysis
The content of saikoside a, saikoside d in the high effective liquid chromatography for measuring bupleurum preparation
1. instrument and reagent high performance liquid chromatograph comprise LC-10ATvp type solvent delivery pump, SPD-10ATvp type UV, visible light detector (day island proper Tianjin company); N2000 chromatographic work station (Zhejiang University's intelligent information Graduate School of Engineering); KQ3200 type ultrasonic washing instrument (Kunshan Ultrasonic Instruments Co., Ltd.), TGL-16G high speed tabletop centrifuge (Anting Scientific Instrument Factory, Shanghai).Trifluoroacetic acid aqueous solution (Merck KGaA company); Water is tri-distilled water (self-control); Other reagent is analytical pure.Radix Bupleuri oral liquid (Pharmaceutical Factory, Zhumadian Prefecture, Henan Province); The Radix Bupleuri oral cavity disintegration tablet (Qianluchun Science and Technology Co., Ltd., Beijing's laboratory provides) of traditional extraction technique preparation; Radix Bupleuri oral cavity disintegration tablet of the present invention (Qianluchun Science and Technology Co., Ltd., Beijing's laboratory provides); Saikoside a reference substance and saikoside d reference substance (Nat'l Pharmaceutical ﹠ Biological Products Control Institute).
2. chromatographic column tested in chromatographic condition and system suitability: the C of Di Ma company
18Post (5 μ m, 250mm * 4.6mm, I.D); Mobile phase: acetonitrile-water (50: 50); Flow velocity: 1.0ml/min; Detect wavelength 203nm; Number of theoretical plate should be not less than 3000 by saikoside a peak compute.
3. reference substance mixed solution preparation precision takes by weighing saikoside a reference substance and each 5.0mg of saikoside d reference substance, puts in the 10ml measuring bottle, adds methanol, ultrasonicly makes dissolving, adds methanol again to scale, shakes up, promptly.
4. standard curve preparation precision is drawn above-mentioned reference substance solution 1.0,2.0,4.0,6.0,8.0,10 μ l, and sample introduction is measured under the said determination condition.The result shows, saikoside a and saikoside d sample size and peak area in 1.00 μ g～10.00 μ g scopes are the good linear relation, and linear equation is respectively: Y=587483X+50138, r=0.9998:Y=604937X+48726, r=0.9999;
5. 10 of test samples are got in the preparation of need testing solution, and accurate the title decided porphyrize, get 1.0g, the accurate title, decide, and puts in the tool plug conical flask, the accurate methanol 20ml that adds claims to decide weight, supersound process 40min, put coldly, claim again to decide weight, supply the weight that subtracts mistake with methanol, shake up, centrifugal (12000rpm) 10min gets supernatant liquid filtering, get subsequent filtrate, promptly.
6. accurate each the 10 μ l of need testing solution that draw of algoscopy inject chromatograph of liquid, measure peak area, calculate content with standard curve.The results are shown in Table 4.
Saikoside a and saikoside d content sum are relatively in table 4 preparation
| Group | Saikoside a and saikoside d content sum * (mg) in the preparation |
| The Radix Bupleuri oral cavity disintegration tablet Radix Bupleuri oral cavity disintegration tablet of the present invention of Radix Bupleuri oral liquid traditional extraction technique preparation | 2.846 2.854 3.257 |
Dose of+expression
Annotate: the each dose of Radix Bupleuri oral cavity disintegration tablet of the present invention is 5.
Six, pharmacology embodiment
1. the bupleurum preparation xylol causes the inhibitory action of mice ear
Get 50 of healthy Kunming mouses, body weight 20～24g.The Radix Bupleuri oral cavity disintegration tablet group, the Radix Bupleuri oral cavity disintegration tablet group of the present invention that are divided into matched group, Radix Bupleuri oral liquid group, injection of Radix Bupleuri group, traditional extraction technique preparation at random.Every group 10, male and female half and half, sub-cage rearing.With the conversion of people's conventional therapy dosage is the dosage of mice.The conversion formula is: tested animal is tried out the body surface area ratio of the body surface area ratio/known animal of dosage=known animals administer amount * tested animal.Matched group gives distilled water, successive administration 7 days, after last 1 administration 30 minutes, two sided coatings dimethylbenzene 0.03ml causes inflammation before and after every mice left side ear, animal is put to death in the cervical vertebra dislocation after 30 minutes, cut two ears along the auricle baseline, lay round auricle at same antimere respectively with 9mm diameter card punch, torsion balance is weighed, the left auricle of every Mus heavily deducts auris dextra sheet weight and is the swelling degree, calculates and respectively organizes the average and the standard deviation of swelling degree, and do the t check, the comparable group differences calculates swelling by following formula and suppresses percentage rate: suppression ratio=(the average swelling degree of the matched group-average swelling degree of administration the group)/average swelling degree of matched group * 100%.The results are shown in Table 5.
Table 5 bupleurum preparation xylol causes the inhibitory action (X ± SD) of mice ear
| Group | Mus number (only) | Ear swelling rate (%) | Suppression ratio (%) |
| The Radix Bupleuri oral cavity disintegration tablet group Radix Bupleuri oral cavity disintegration tablet of the present invention group of matched group Radix Bupleuri oral liquid group injection of Radix Bupleuri group traditional extraction technique preparation | 10 10 10 10 10 | 14.06±2.18 11.47±2.54 * 10.72±3.36 * 11.13±2.88 * 9.82±3.47 *# | - 18.4 23.8 20.8 30.2 |
Annotate: compare with matched group:
*P＜001;
Compare with the Radix Bupleuri oral cavity disintegration tablet group of Radix Bupleuri oral liquid group, injection of Radix Bupleuri group, traditional handicraft preparation: #P＜0.05
The Radix Bupleuri oral cavity disintegration tablet of Radix Bupleuri oral liquid, injection of Radix Bupleuri, traditional extraction technique preparation and Radix Bupleuri oral cavity disintegration tablet xylol of the present invention cause mice ear all inhibitory action (P＜0.01); Radix Bupleuri oral cavity disintegration tablet of the present invention is compared with the Radix Bupleuri oral cavity disintegration tablet of Radix Bupleuri oral liquid, injection of Radix Bupleuri, traditional extraction technique preparation, and xylol causes mice ear also variant (P＜0.05).Illustrate: the pharmacological action of Radix Bupleuri oral cavity disintegration tablet of the present invention is better than the Radix Bupleuri oral cavity disintegration tablet of Radix Bupleuri oral liquid, injection of Radix Bupleuri, traditional extraction technique preparation.
2. hot-plate analgesic test
Water temperature is constant in 55 ± 0.5 ℃, gets 50 of the qualified mices of preliminary election, divides 5 groups at random.The Radix Bupleuri oral cavity disintegration tablet group and the Radix Bupleuri oral cavity disintegration tablet group of the present invention of matched group, Radix Bupleuri oral liquid group, injection of Radix Bupleuri group, traditional extraction technique preparation.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 6.
Table 6 'Qingyan ' xylol causes the inhibitory action (X ± SD) of mice ear
| Group | Mus number (only) | Pain threshold (s) | |
| Before the administration | After the administration | ||
| The Radix Bupleuri oral cavity disintegration tablet group of matched group Radix Bupleuri oral liquid group injection of Radix Bupleuri group traditional extraction technique preparation | 10 10 10 10 | 17.83±4.23 17.47±4.73 17.24±4.47 17.68±4.52 | 18.75+3.18 23.38+7.64 * 24.16+5.83 * 23.74±5.47 * |
| Radix Bupleuri oral cavity disintegration tablet group of the present invention | 10 | 17.94±4.55 | 27.33+5.22 *# |
Annotate: compare with matched group:
*P＜0.01;
Compare with the Radix Bupleuri oral cavity disintegration tablet group of Radix Bupleuri oral liquid group, Radix Bupleuri oral cavity disintegration tablet group, traditional extraction technique preparation: #P＜0.05
The Radix Bupleuri oral cavity disintegration tablet of Radix Bupleuri oral cavity disintegration tablet of the present invention, Radix Bupleuri oral liquid, injection of Radix Bupleuri and traditional extraction technique preparation all can significantly increase the pain threshold (P＜0.01) of mice; Radix Bupleuri oral cavity disintegration tablet of the present invention is compared with the Radix Bupleuri oral cavity disintegration tablet of Radix Bupleuri oral liquid, injection of Radix Bupleuri, traditional extraction technique preparation, and pain threshold improves also variant (P＜0.05).Illustrate: the pharmacological action of Radix Bupleuri oral cavity disintegration tablet of the present invention is better than the Radix Bupleuri oral cavity disintegration tablet of Radix Bupleuri oral liquid, injection of Radix Bupleuri and traditional extraction technique preparation.
Above pharmacological evaluation proves that the Radix Bupleuri oral cavity disintegration tablet for preparing with new technology has better therapeutic effect.
Six, preparation embodiment
Embodiment 1
(1) raw medicinal material: Radix Bupleuri 1000g;
(2) get the Radix Bupleuri pulverizing medicinal materials, cross 40 mesh sieves, use supercritical extraction, extracting pressure is 12Mpa, 30 ℃ of cycling extractions 2 hours, obtains supercritical extract 6.8g; Supercritical extract is slowly added in β-CD aqueous solution, and 50 ℃ were stirred 3 hours, continued under the room temperature to stir 5 hours, filtered, and obtained clathrate 34g;
(3) with above-mentioned medicinal residues with twice of 85% ethanol extraction; Be equivalent to medical material weight 6-10 solvent doubly each the adding; Extracted 1-3 hour for the first time, extracted 1-2 hour for the second time; Merge ethanol extract, filter, filtrate is concentrated into does not have the alcohol flavor; Last macroporous adsorbent resin, with the washing of 6 times of amounts, reuse 50% ethanol elution is collected ethanol elution earlier; Concentrating under reduced pressure is concentrated into relative density and is 1.17 extractum in the time of 50 ℃, drying obtains ethanol extraction 28g;
(4) preparation prescription is:
Clathrate 34g
Extract 28g
Nano micro crystal cellulose 177g
Erythritol 15g
Low-substituted hydroxypropyl methylcellulose 40g
Magnesium stearate 6g
(5) clathrate, ethanol extraction are mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain 750 of oral cavity disintegration tablets.
Embodiment 2
(1) raw medicinal material: Radix Bupleuri 1000g;
(2) get the Radix Bupleuri pulverizing medicinal materials, cross 30 mesh sieves, use supercritical extraction, extracting pressure is 36Mpa, 65 ℃ of cycling extractions 3 hours, obtains supercritical extract 10.7g; Supercritical extract is slowly added in HP-β-CD aqueous solution, and 50 ℃ were stirred 3 hours, continued under the room temperature to stir 5 hours, filtered, and obtained clathrate 55g;
(3) with above-mentioned medicinal residues with twice of 70% ethanol extraction; Each solvent that is equivalent to 10 times of medical material weight that adds; Extracted 2 hours for the first time, extracted 1 hour for the second time; Merge ethanol extract, filter, filtrate is concentrated into does not have the alcohol flavor; Last macroporous adsorbent resin, earlier with the washing of 4 times of amounts, reuse 60% ethanol elution, the collection ethanol elution: concentrating under reduced pressure, be concentrated into relative density in the time of 50 ℃ and be 1.23 extractum, drying obtains ethanol extraction 26g;
(4) preparation prescription is:
Clathrate 55g
Extract 26g
Microcrystalline Cellulose 125g
Erythritol 36g
Carboxymethyl starch sodium 53g
Pulvis Talci 5g
(5) clathrate, ethanol extraction are mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain 750 of oral cavity disintegration tablets.
Embodiment 3
(1) raw medicinal material: Radix Bupleuri 1000g;
(2) get the Radix Bupleuri pulverizing medicinal materials, cross 20 mesh sieves, use supercritical extraction, extracting pressure is 48Mpa, 50 ℃ of cycling extractions 2 hours, obtains supercritical extract 15.8g; Supercritical extract is slowly added in HP-β-CD aqueous solution, and 50 ℃ were stirred 3 hours, continued under the room temperature to stir 5 hours, filtered, and obtained clathrate 87g;
(3) with above-mentioned medicinal residues with twice of 58% ethanol extraction; Each solvent that is equivalent to 6 times of medical material weight that adds; Extracted 2 hours for the first time, extracted 1 hour for the second time; Merge ethanol extract, filter, filtrate is concentrated into does not have the alcohol flavor; Last macroporous adsorbent resin, with the washing of 5 times of amounts, reuse 70% ethanol elution is collected ethanol elution earlier; Concentrating under reduced pressure is concentrated into relative density and is 1.28 extractum in the time of 50 ℃, drying obtains ethanol extraction 22g;
(4) preparation prescription is:
Clathrate 87g
Extract 22g
Nano micro crystal cellulose 118g
Erythritol 20g
Crosslinked carboxymethyl fecula sodium 43g
Stevioside 7g
Stepanol MG 3g
(5) clathrate, ethanol extraction are mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain 750 of oral cavity disintegration tablets.
Embodiment 4
(1) raw medicinal material: Radix Bupleuri 1000g;
(2) get the Radix Bupleuri pulverizing medicinal materials, cross 20 mesh sieves, use supercritical extraction, extracting pressure is 27Mpa, 40 ℃ of cycling extractions 4 hours, obtains supercritical extract 18.7g; Supercritical extract is slowly added in β-CD aqueous solution, and 50 ℃ were stirred 3 hours, continued under the room temperature to stir 5 hours, filtered, and obtained wrapping platform thing 112g;
(3) with above-mentioned medicinal residues with twice of 42% ethanol extraction; Each solvent that is equivalent to 8 times of medical material weight that adds; Extracted 2 hours for the first time, extracted 1 hour for the second time; Merge ethanol extract, filter, filtrate is concentrated into does not have the alcohol flavor; Last macroporous adsorbent resin, with the washing of 3 times of amounts, reuse 80% ethanol elution is collected ethanol elution earlier; Concentrating under reduced pressure is concentrated into relative density and is 1.20 extractum in the time of 50 ℃, drying obtains ethanol extraction 17g;
(4) preparation prescription is:
Clathrate 112g
Extract 17g
Microcrystalline Cellulose 117g
Erythritol 19g
Crospolyvinylpyrrolidone 28g
Stevioside 5g
Magnesium stearate 2g
(5) clathrate, ethanol extraction are mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain 750 of oral cavity disintegration tablets.
Claims (8)
1. Radix Bupleuri oral cavity disintegration tablet is characterized in that it is made up of cyclodextrin clathrate 3-12 weight portion, ethanol extraction 1.5-3 weight portion and the pharmaceutic adjuvant of the supercritical extract of Radix Bupleuri medical material; Disintegrating agent 4-10 weight portion, filler 10-20 weight portion, correctives 0.1-1 weight portion, lubricant 0.1-1 weight portion in the pharmaceutic adjuvant; Wherein used disintegrating agent is the compound disintegrating agent that contains erythritol, and the weight percentage of erythritol is 30%-70%.
2. oral cavity disintegration tablet according to claim 1, compound disintegrating agent wherein is made up of erythritol, chitin, low-substituted hydroxypropyl methylcellulose, carboxymethyl starch sodium, crosslinked carboxymethyl fecula sodium, insoluble crospolyvinylpyrrolidone, and the weight percentage of its mesoerythrit is 30%-70%.
3. a kind of Radix Bupleuri oral cavity disintegration tablet as claimed in claim 1, its preparation method may further comprise the steps:
(1) raw medicinal material consists of: Radix Bupleuri 100 weight portions;
(2) get the Radix Bupleuri pulverizing medicinal materials, cross the 20-60 mesh sieve, use supercritical extraction, extracting pressure be 10-50MPa. at 20-70 ℃ of cycling extraction 1-4 hour, obtain supercritical extract; Supercritical extract is slowly added 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, filtered, and obtained clathrate;
(3) with above-mentioned medicinal residues with twice of the ethanol extraction of 40%-85%; Be equivalent to the solvent that medical material weight 6-10 doubly measures each the adding; Extracted 2 hours for the first time, extracted 1 hour for the second time; Merge ethanol extract, filter, filtrate is concentrated into does not have the alcohol flavor; Last macroporous adsorbent resin, the washing of doubly measuring earlier with 3-6, reuse 50%-80% ethanol elution is collected ethanol elution; Concentrating under reduced pressure is concentrated into the extractum that relative density is 1.15-1.30 in the time of 50 ℃, drying obtains ethanol extraction;
(4) clathrate, ethanol extraction 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, supercritical extract is the 0.5-2 weight portion in the cyclodextrin clathrate wherein.
5. according to claim 1 or 3 described oral cavity disintegration tablets, wherein macroporous adsorbent resin is nonpolar macroporous adsorption resin or low pole macroporous adsorbent resin.
6. according to claim 1 or 3 described oral cavity disintegration tablets, wherein filler is a kind of in microcrystalline Cellulose or the nano micro crystal cellulose.
7. according to claim 1 or 3 described oral cavity disintegration tablets, wherein correctives is a kind of in former times of mannitol or Flos Chrysanthemi.
8. according to claim 1 or 3 described oral cavity disintegration tablets, wherein lubricant is a kind of in magnesium stearate or Pulvis Talci or the Stepanol MG.
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| CN1148977A (en) * | 1996-08-25 | 1997-05-07 | 重庆祥慧医药高新技术研究所 | Prescription of Yiganning capsule for curing hepatitis B and its production process |
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| CN1148977A (en) * | 1996-08-25 | 1997-05-07 | 重庆祥慧医药高新技术研究所 | Prescription of Yiganning capsule for curing hepatitis B and its production process |
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| Title |
|---|
| 口腔崩解片研制简介 李先何等，实用中西医结合临床2003，第3卷第2期 2003 * |
| 口腔崩解片研制简介 李先何等，实用中西医结合临床2003，第3卷第2期 2003;西藏科技 宋金玉，32-39，中药制剂发展的问题 2003 * |
| 西藏科技 宋金玉，32-39，中药制剂发展的问题 2003 * |
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