CN1318020C - Blood nourishing, brain refreshing orally disintegrating tablet and its preparation process - Google Patents
Blood nourishing, brain refreshing orally disintegrating tablet and its preparation process Download PDFInfo
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- CN1318020C CN1318020C CNB2004100498507A CN200410049850A CN1318020C CN 1318020 C CN1318020 C CN 1318020C CN B2004100498507 A CNB2004100498507 A CN B2004100498507A CN 200410049850 A CN200410049850 A CN 200410049850A CN 1318020 C CN1318020 C CN 1318020C
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- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 239000008280 blood Substances 0.000 title abstract description 7
- 210000004369 blood Anatomy 0.000 title abstract description 7
- 239000006191 orally-disintegrating tablet Substances 0.000 title abstract description 7
- 210000004556 brain Anatomy 0.000 title abstract 2
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 74
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 claims abstract description 43
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 claims abstract description 43
- 239000004386 Erythritol Substances 0.000 claims abstract description 38
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- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical class OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 12
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 8
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- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 5
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- 239000003826 tablet Substances 0.000 description 66
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- KSEBMYQBYZTDHS-HWKANZROSA-M (E)-Ferulic acid Natural products COC1=CC(\C=C\C([O-])=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-M 0.000 description 5
- 230000017531 blood circulation Effects 0.000 description 5
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- 229940114124 ferulic acid Drugs 0.000 description 5
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- 241000282326 Felis catus Species 0.000 description 4
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 206010019233 Headaches Diseases 0.000 description 2
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- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
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- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
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Abstract
The present invention discloses an orally disintegrating tablet with blood nourishing and mind refreshing effect and a preparation method thereof. The orally disintegrating tablet is prepared from effective components extracted from 11 kinds of traditional Chinese medicine including angelica, hemlock parsley, and the like and pharmaceutical adjuvant; a composite disintegrating agent containing erythritol is also used; erythritol and chitin or low-substituted hydroxypropyl cellulose or sodium carboxymethyl starch or crosslinked sodium carboxymethyl starch or non-soluble crosslinked polyvinyl pyrrolidone are combined into the composite disintegrating agent according to a certain proportion. The erythritol has the effect of a flavoring agent so that the dosage of the pharmaceutical adjuvant of the preparation is reduced. Pharmacological experiments show that the orally disintegrating tablet with blood nourishing and brain refreshing effect has the characteristics of quick disintegration, rapid effect taking and excellent pharmacological action.
Description
Technical field
The invention belongs to technical field of traditional Chinese medicine pharmacy, be specifically related to a kind of blood-nourishing and brain-refreshing oral cavity disintegration tablet and preparation method thereof.
Background technology
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 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.
The YANGXUE QINGNAO KELI of market sale has certain effect in clinical practice, but because it is a kind of medicine that is used for treating headache, in the process of taking, need warm water to take after mixing it with water, make the odor dispersion of Chinese medicine come out, the patient is not easy to take, and granule onset simultaneously is slow, can not fine, rapid alleviation have a headache; Do not retrieve patent about the blood-nourishing and brain-refreshing oral cavity disintegration tablet.
Summary of the invention
For these reasons, 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 does not have 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 does not have 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 to blood-nourishing and brain-refreshing ten simply Chinese medicine extract, the effective site that obtains is mixed with into oral cavity disintegration tablet with pharmaceutic adjuvant, has that disintegrate is fast, onset is rapid, the better characteristics of pharmacological action.
The present invention is achieved through the following technical solutions.
One. process recipes
(1) crude drug of the present invention is:
Radix Angelicae Sinensis 300-350 weight portion, Rhizoma Chuanxiong 300-350 weight portion, Radix Paeoniae Alba 250-300 weight portion, Radix Rehmanniae Preparata 250-300 weight portion, Ramulus Uncariae Cum Uncis 650-700 weight portion, Caulis Spatholobi 650-700 weight portion, Spica Prunellae 650-700 weight portion, Semen Cassiae 650-700 weight portion, Concha Margaritifera 650-700 weight portion, Rhizoma Corydalis 300-350 weight portion, Herba Asari 60-70 weight portion;
(2) crude drug of the present invention is:
Radix Angelicae Sinensis 338 weight portions, Rhizoma Chuanxiong 338 weight portions, the Radix Paeoniae Alba 270.3 weight portions, Radix Rehmanniae Preparata 270.3 weight portions, Ramulus Uncariae Cum Uncis 675.7 weight portions, Caulis Spatholobi 675.7 weight portions, Spica Prunellae 675.7 weight portions, Semen Cassiae 675.7 weight portions, Concha Margaritifera 675.7 weight portions, Rhizoma Corydalis 338 weight portions, Herba Asari 67.3 weight portions;
(3) get above-mentioned ten Chinese medicines simply, put into the extraction pot of Chinese medicine dynamic extraction multifunction extracting device, add water 6-20 doubly, extract 2-5 time, each 2-5 hour, merge extractive liquid,, relative density is the extractum of 1.20-1.25 when being concentrated to 20 ℃, add the ethanol of 60%-80%, left standstill 24 hours, get supernatant, reclaim ethanol to most, vacuum concentration, drying obtains effective ingredient in Chinese;
(4) effective ingredient in Chinese 50-110 weight portion is mixed with the compound disintegrating agent 57-75 of the present invention weight portion, add filler 128-167 weight portion, granulate, add lubricant 5-8 weight portion, tabletting obtains the blood-nourishing and brain-refreshing oral cavity disintegration tablet.
Compound disintegrating agent is made up of erythritol and chitin or low-substituted hydroxypropyl methylcellulose or carboxymethyl starch sodium or crosslinked carboxymethyl fecula sodium or insoluble crospolyvinylpyrrolidone, and the weight percentage of compound disintegrating agent mesoerythrit is 30%-70%.
A kind of for in the microcrystalline Cellulose, nano micro crystal cellulose of filler.
Lubricant is a kind of in magnesium stearate, Pulvis Talci, the Stepanol MG.
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 calculating wettability (%) sees 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 (37 ℃) W/V | Viscosity (37 ℃) mpa.s | Wettability % | Volume increases percent % |
| 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 Pharmacopoeia of People's Republic of China, utilize the disintegrate tester to measure, 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 | 4.1 3.9 2.1 2.2 2.2 2.1 2.0 1.9 | 22.1 21.6 9.3. 8.6 8.1 8.6 9.3 9.6 | 42.1 43.6 26.3 25.2 26.1 26.9 26.8 35.9 | 51.2 52.9 32.9 28.3 26.7 27.4 27.3 38.6 | Have seldom | Bad generally carefully |
| 9 10 11 | 1.8 4.6 4.8 | 10.2 33.9 36.5 | 35.6 54.1 55.6 | 39.1 62.9 62.8 | Seldom having much has a lot | Good very poor |
Change above-mentioned chitin, crosslinked carboxymethyl fecula sodium into chitosan, low-substituted hydroxypropyl methylcellulose, crosslinked carboxymethyl fecula sodium, insoluble crospolyvinylpyrrolidone, experimentize, the result of experiment conclusion and table 2 is close.
Conclusion: 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. check and analysis
The check and analysis of ferulic acid
Experiment medicine: ferulic acid reference substance (Nat'l Pharmaceutical ﹠ Biological Products Control Institute);
YANGXUE QINGNAO KELI (Tianjin Tasly Pharmaceutical Co., Ltd)
Blood-nourishing and brain-refreshing oral cavity disintegration tablet (Qianluchun Science and Technology Co., Ltd., Beijing's laboratory provides)
Methanol, glacial acetic acid, ethyl acetate (AR, Beijing Chemical Plant)
Experimental apparatus: TG332A microanalytical balance (Shanghai balance equipment factory)
Company of U.S. water department high performance liquid chromatograph, the M441 UV-detector
Experimental technique: precision takes by weighing ferulic acid reference substance 4.02mg, put in the 10ml volumetric flask, the ethyl acetate dissolving also is diluted to scale, shakes up, and draws 0.1ml, put in the 5ml volumetric flask, with mobile phase dilution scale, shake up sample introduction, measure peak area, the regression equation that calculates standard curve is Y=(16.46+3.160X) * 10
3R=09993
Get 5 bags of YANGXUE QINGNAO KELI, 5 of oral cavity disintegration tablets, porphyrize is got about 1 gram, and accurate the title decides, and puts in the 50ml tool plug triangular flask, add methanol-acetate solution (95: 5) 20ml, close plug, jolting, placement is spent the night, the accurate supernatant 10ml evaporate to dryness of drawing, residue water 5ml dissolving filters C on the filtrate
18-The pretreatment pillar is collected 30% meoh eluate, places in the 1Oml volumetric flask, puts scale, draws 50ul, and last sample according to peak area and two kinds of preparation ferulaic acid contents of regression equation calculation, sees Table 3
Content of ferulic acid in the table 3 blood-nourishing and brain-refreshing preparation
| The medicine group | Ferulaic acid content |
| YANGXUE QINGNAO KELI blood-nourishing and brain-refreshing oral cavity disintegration tablet | 78.69ug/ bag 84.54ug/ sheet |
Five. the preparation disintegration time mensuration
In order to prove absolutely that the employed compound disintegrating agent of blood-nourishing and brain-refreshing 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 4 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.
The disintegration time mensuration of the different disintegrating agents of table 4
| The experiment number | 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) | 30.2 16..9 27.6 16.8 38.3 15.2 40.4 14.6 33.4 13.4 |
The result: the oral cavity disintegration tablet that uses compound disintegrating agent is in 13.4-16.9 all disintegrates and by No. 2 sieves in second; The oral cavity disintegration tablet that uses single disintegrating agent is in 27.6-40.4 all disintegrates and by No. 2 sieves in second.Illustrate that compound disintegrating agent of the present invention has disintegrate characteristics rapidly really.
Six. the disintegration contrast experiment
Get blood-nourishing and brain-refreshing oral cavity disintegration tablet of the present invention, place the beaker of the 10ml that fills 37 ℃ of water of 5ml, stir with 30 rev/mins speed.Oral cavity disintegration tablet of the present invention whole disintegrates in 20 seconds are also sieved by No. 2.
Get two of with cover, grid lattice plate hermetic containers, under the lattice plate, put into the water of equivalent, add a cover, after making hermetic container humidity reach 90%, simultaneously put into 10 bags of 10 blood-nourishing and brain-refreshing oral cavity disintegration tablets, YANGXUE QINGNAO KELI respectively on two container lattice plates, sampling in 10 minutes, 15 minutes, 20 minutes, 25 minutes is according to above-mentioned detection method, the results are shown in Table 5
Table 5 disintegration contrast experiment (ferulaic acid content ug)
| Group | 10 minutes | 15 minutes | 20 minutes | 25 minutes |
| YANGXUE QINGNAO KELI blood-nourishing and brain-refreshing oral cavity disintegration tablet | - 706.2 | - 779.3 | - 841.2 | - 841.2 |
---representative does not detect content
Conclusion: by above-mentioned disintegration experiment, we can obtain, under the condition of good moisture, oral cavity disintegration tablet of the present invention, can be good at disintegrate, and granule is not only without any disintegrate, and the phenomenon that is bonded together in addition, shows that fully Orally-disintegrating tablet of the present invention has good disintegration.
Seven. the dissolution experiment
1. instrument and reagent: the full-automatic digestion instrument of SR-6 type (U.S. Hanson company); Distilled water (self-control); YANGXUE QINGNAO KELI (Tianjin Tasly Pharmaceutical Co., Ltd); Blood-nourishing and brain-refreshing oral cavity disintegration tablet (Qianluchun Science and Technology Co., Ltd., Beijing's laboratory provides).
2. experimental technique: measure the distilled water of handling through the degassing that each container fills 100ml by second method in the dissolution method (" 2000 editions two appendix XC of Chinese pharmacopoeia), heating makes water temperature remain on 37 ℃ ± 0.5 ℃, and rotating speed of agitator is 50 rev/mins.Put into 1 of blood-nourishing and brain-refreshing oral cavity disintegration tablet of the present invention, in the time of 20 minutes, get 2ml solution, centrifugal 10 minutes (12000rpm), supernatant is as need testing solution.Measure with above-mentioned check and analysis ferulic acid assay method.The results are shown in Table 5.
The dissolution of two kinds of medicines of table 6 relatively
| The medicine group | (min) ferulaic acid content sample time (ug) | |||||||
| 0.5 | 1 | 2 | 4 | 8 | 12 | 16 | 20 | |
| YANGXUE QINGNAO KELI blood-nourishing and brain-refreshing oral cavity disintegration tablet | 9.86 48.12 | 13.64 59.35 | 25.12 68.13 | 40.01 79.56 | 51.23 83.89 | 63.12 84.12 | 71.48 84.12 | 77.56 84.12 |
Conclusion: strippings in 30 seconds of blood-nourishing and brain-refreshing oral cavity disintegration tablet of the present invention are more than 50%, in the time of 8 minutes dissolving almost completely, prove absolutely Orally-disintegrating tablet of the present invention have disintegration rate fast, reach the fast characteristics of blood drug level.
Seven. pharmacology embodiment
Influence to the cat common carotid artery blood flow
Laboratory animal: the cat male and female are usefulness all, totally 80, is divided into 4 groups;
Experimental drug: ZHENNAONING JIAONANG (Jilin Dongbao of Tonghua Pharma Inc.)
YANGXUE QINGNAO KELI (Tianjin Tasly Pharmaceutical Co., Ltd);
Blood-nourishing and brain-refreshing oral cavity disintegration tablet (Qianluchun Science and Technology Co., Ltd., Beijing's laboratory provides).
Experimental apparatus: KM600 type eight road physiology monitors;
Experimental technique: cat with pentobarbital sodium 30mg/kg intraperitoneal anesthesia, is separated carotid artery, after the carotid sinus bifurcation connects the bundle external carotid artery, place probe, connect electromagnetic flowmeter, the record blood flow at the common carotid artery place; Behind the gastric infusion, observe and record respectively, see Table 6:
The influence of table 7 pair cat common carotid artery blood flow
| The medicine group | Number of animals (only) | Dosage mg/kg | Blood flow before the administration | Blood flow after the administration | |||
| 5 minutes | 15 minutes | 20 minutes | 30 minutes | ||||
| Normal saline ZHENNAONING JIAONANG blood-nourishing and brain-refreshing | 10 10 10 | - 15.6 15.6 | 2.01±2.31 2.11±2.58 2.14±2.04 | 0.14±0.10 0.48±0.34 0.48±0.52 | 0.20±0.20 0.59±0.35 * 0.69±0.52 | 0.20±0.18 0.48±0.26 * 0.87±0.54 | 0.13±0.12 0.10±0.16 0.65±0.58 |
| Granule blood-nourishing and brain-refreshing oral cavity disintegration tablet | 10 | 15.6 | 2.67±2.05 | * 0.88±0.53 ** | ** 0.71±0.55 ** | ** 0.69±0.58 ** | * 0.60±056 * |
Annotate: compare with the blank group
*P＜0.01,
*P＜0.05
Conclusion: pharmacological evaluation shows, rapid (oral cavity disintegration tablet promptly reached the blood drug level peak value in 5 minutes to the speed that Orally-disintegrating tablet of the present invention reaches blood drug level than YANGXUE QINGNAO KELI, granule just reached at 20 minutes), pharmacological action is close at 15 minutes, but the pharmacological action of oral cavity disintegration tablet is better than ZHENNAONING JIAONANG.
Eight. preparation embodiment
Embodiment 1
(1) crude drug of the present invention is:
Radix Angelicae Sinensis 300 grams, Rhizoma Chuanxiong 300 grams, the Radix Paeoniae Alba 250 grams, Radix Rehmanniae Preparata 250 grams, Ramulus Uncariae Cum Uncis 650 grams, Caulis Spatholobi 650 grams, Spica Prunellae 650 grams, Semen Cassiae 650 grams, Concha Margaritifera 650 grams, Rhizoma Corydalis 300 grams, Herba Asari 60 grams;
(2) get above-mentioned ten Chinese medicines simply, put into the extraction pot of Chinese medicine dynamic extraction multifunction extracting device, add 6 times in water, extract 2 times, each 2 hours, merge extractive liquid,, relative density is 1.20 extractum when being concentrated to 20 ℃, the ethanol of adding 60% left standstill 24 hours, got supernatant, reclaim ethanol to most, vacuum concentration, drying obtains effective ingredient in Chinese 50 grams;
(3) effective ingredient in Chinese 50 grams are mixed with compound disintegrating agent 75 grams of the present invention, add filler microcrystalline Cellulose 167 grams, granulate, add magnesium stearate lubricant 8 grams, tabletting obtains 1000 of blood-nourishing and brain-refreshing Orally disintegratings.
Compound disintegrating agent is made up of erythritol and chitin or low-substituted hydroxypropyl methylcellulose or carboxymethyl starch sodium or crosslinked carboxymethyl fecula sodium or insoluble crospolyvinylpyrrolidone, and the weight percentage of compound disintegrating agent mesoerythrit is 30%-70%.
Embodiment 2
(1) crude drug of the present invention is:
Radix Angelicae Sinensis 350 gram, Rhizoma Chuanxiong 350 grams, the Radix Paeoniae Alba 300 grams, Radix Rehmanniae Preparata 300 grams, Ramulus Uncariae Cum Uncis 700 can, Caulis Spatholobi 700 grams, Spica Prunellae 700 grams, Semen Cassiae 700 grams, Concha Margaritifera 700 grams, Rhizoma Corydalis 350 grams, Herba Asari 70 grams;
(2) get above-mentioned ten Chinese medicines simply, put into the extraction pot of Chinese medicine dynamic extraction multifunction extracting device, add 20 times in water, extract 5 times, each 5 hours, merge extractive liquid,, relative density is 1.25 extractum when being concentrated to 20 ℃, the ethanol of adding 80% left standstill 24 hours, got supernatant, reclaim ethanol to most, vacuum concentration, drying obtains effective ingredient in Chinese;
(3) effective ingredient in Chinese 110 grams are mixed with compound disintegrating agent 57 grams of the present invention, add filler nano micro crystal cellulose 128 gram weight parts, granulate, add lubricant Pulvis Talci 5 grams, tabletting obtains 1000 of blood-nourishing and brain-refreshing oral cavity disintegration tablets.
Compound disintegrating agent is made up of erythritol and chitin or low-substituted hydroxypropyl methylcellulose or carboxymethyl starch sodium or crosslinked carboxymethyl fecula sodium or insoluble crospolyvinylpyrrolidone, and the weight percentage of compound disintegrating agent mesoerythrit is 30%-70%.
Embodiment 3
(1) crude drug of the present invention is:
Radix Angelicae Sinensis 310 grams, Rhizoma Chuanxiong 310 grams, the Radix Paeoniae Alba 260 grams, Radix Rehmanniae Preparata 260 grams, Ramulus Uncariae Cum Uncis 660 grams, Caulis Spatholobi 660 grams, Spica Prunellae 660 grams, Semen Cassiae 660 grams, Concha Margaritifera 660 grams, Rhizoma Corydalis 310 grams, Herba Asari 65 grams;
(2) get above-mentioned ten Chinese medicines simply, put into the extraction pot of Chinese medicine dynamic extraction multifunction extracting device, add 10 times in water, extract 3 times, each 3 hours, merge extractive liquid,, relative density is 1.22 extractum when being concentrated to 20 ℃, the ethanol of adding 65% left standstill 24 hours, got supernatant, reclaim ethanol to most, vacuum concentration, drying obtains effective ingredient in Chinese;
(4) with effective ingredient in Chinese 75 grams and compound disintegrating agent 60 grams of the present invention, add filler nano micro crystal cellulose 159 grams, granulate, add lubricant Stepanol MG 6 grams, tabletting obtains 1000 of blood-nourishing and brain-refreshing oral cavity disintegration tablets.
Compound disintegrating agent is made up of erythritol and chitin or low-substituted hydroxypropyl methylcellulose or carboxymethyl starch sodium or crosslinked carboxymethyl fecula sodium or insoluble crospolyvinylpyrrolidone, and the weight percentage of compound disintegrating agent mesoerythrit is 30%-70%.
Embodiment 4
(1) crude drug of the present invention is:
Radix Angelicae Sinensis 338 grams, Rhizoma Chuanxiong 338 grams, the Radix Paeoniae Alba 270.3 grams, Radix Rehmanniae Preparata 270.3 grams, Ramulus Uncariae Cum Uncis 675.7 grams, Caulis Spatholobi 675.7 grams, Spica Prunellae 675.7 grams, Semen Cassiae 675.7 grams, Concha Margaritifera 675.7 grams, Rhizoma Corydalis 338 grams, Herba Asari 67.3 grams;
(2) get above-mentioned ten Chinese medicines simply, put into the extraction pot of Chinese medicine dynamic extraction multifunction extracting device, add 12 times in water, extract 4 times, each 4 hours, merge extractive liquid,, relative density is 1.24 extractum when being concentrated to 20 ℃, the ethanol of adding 70% left standstill 24 hours, got supernatant, reclaim ethanol to most, vacuum concentration, drying obtains effective ingredient in Chinese;
(3) effective ingredient in Chinese 80 grams are mixed with compound disintegrating agent 69 grams of the present invention, add filler microcrystalline Cellulose 144 grams, granulate, add lubricant Pulvis Talci 7 grams, tabletting obtains 1000 of blood-nourishing and brain-refreshing oral cavity disintegration tablets.
Compound disintegrating agent is made up of erythritol and chitin or low-substituted hydroxypropyl methylcellulose or carboxymethyl starch sodium or crosslinked carboxymethyl fecula sodium or insoluble crospolyvinylpyrrolidone, and the weight percentage of compound disintegrating agent mesoerythrit is 30%-70%.
Embodiment 5
(1) crude drug of the present invention is:
Radix Angelicae Sinensis 338 grams, Rhizoma Chuanxiong 338 grams, the Radix Paeoniae Alba 270.3 grams, Radix Rehmanniae Preparata 270.3 grams, Ramulus Uncariae Cum Uncis 675.7 grams, Caulis Spatholobi 675.7 grams, Spica Prunellae 675.7 grams, Semen Cassiae 675.7 grams, Concha Margaritifera 675.7 grams, Rhizoma Corydalis 338 grams, Herba Asari 67.3 grams;
(2) get above-mentioned ten Chinese medicines simply, put into the extraction pot of Chinese medicine dynamic extraction multifunction extracting device, add 16 times in water, extract 4 times, each 3 hours, merge extractive liquid,, relative density is 1.22 extractum when being concentrated to 20 ℃, the ethanol of adding 75% left standstill 24 hours, got supernatant, reclaim ethanol to most, vacuum concentration, drying obtains effective ingredient in Chinese;
(3) effective ingredient in Chinese 95 grams are mixed with compound disintegrating agent 62 grams of the present invention, add filler microcrystalline Cellulose 136 grams, granulate, add lubricant Stepanol MG 7 grams, tabletting obtains 1000 of blood-nourishing and brain-refreshing oral cavity disintegration tablets.
Compound disintegrating agent is made up of erythritol and chitin or low-substituted hydroxypropyl methylcellulose or carboxymethyl starch sodium or crosslinked carboxymethyl fecula sodium or insoluble crospolyvinylpyrrolidone, and the weight percentage of compound disintegrating agent mesoerythrit is 30%-70%.
Embodiment 6
(1) crude drug of the present invention is:
Radix Angelicae Sinensis 338 grams, Rhizoma Chuanxiong 338 grams, the Radix Paeoniae Alba 270.3 grams, Radix Rehmanniae Preparata 270.3 grams, Ramulus Uncariae Cum Uncis 675.7 grams, Caulis Spatholobi 675.7 grams, Spica Prunellae 675.7 grams, Semen Cassiae 675.7 grams, Concha Margaritifera 675.7 grams, Rhizoma Corydalis 338 grams, Herba Asari 67.3 grams;
(2) get above-mentioned ten Chinese medicines simply, put into the extraction pot of Chinese medicine dynamic extraction multifunction extracting device, add 18 times in water, extract 4 times, each 3 hours, merge extractive liquid,, relative density is 1.24 extractum when being concentrated to 20 ℃, the ethanol of adding 65% left standstill 24 hours, got supernatant, reclaim ethanol to most, vacuum concentration, drying obtains effective ingredient in Chinese;
(3) effective ingredient in Chinese 102 grams are mixed with compound disintegrating agent 59 grams of the present invention, add filler nano micro crystal cellulose 131 grams, granulate, add lubricant Stepanol MG 8 grams, tabletting obtains 1000 of blood-nourishing and brain-refreshing oral cavity disintegration tablets.
Compound disintegrating agent is made up of erythritol and chitin or low-substituted hydroxypropyl methylcellulose or carboxymethyl starch sodium or crosslinked carboxymethyl fecula sodium or insoluble crospolyvinylpyrrolidone, and the weight percentage of compound disintegrating agent mesoerythrit is 30%-70%.
Embodiment 7
(1) crude drug of the present invention is:
Radix Angelicae Sinensis 3380 grams, Rhizoma Chuanxiong 3380 grams, the Radix Paeoniae Alba 2703 grams, Radix Rehmanniae Preparata 2703 grams, Ramulus Uncariae Cum Uncis 6757 grams, Caulis Spatholobi 6757 grams, Spica Prunellae 6757 grams, Semen Cassiae 6757 grams, Concha Margaritifera 6757 grams, Rhizoma Corydalis 338 grams, Herba Asari 673 grams;
(2) get above-mentioned ten Chinese medicines simply, put into the extraction pot of Chinese medicine dynamic extraction multifunction extracting device, add 15 times in water, extract 3 times, each 3 hours, merge extractive liquid,, relative density is 1.22 extractum when being concentrated to 20 ℃, the ethanol of adding 75% left standstill 24 hours, got supernatant, reclaim ethanol to most, vacuum concentration, drying obtains effective ingredient in Chinese;
(3) effective ingredient in Chinese 980 grams are mixed with compound disintegrating agent 582 grams of the present invention, add filler nano micro crystal cellulose 1363 grams, granulate, add lubricant Stepanol MG 75 grams, tabletting obtains 10000 of blood-nourishing and brain-refreshing oral cavity disintegration tablets.
Compound disintegrating agent is made up of erythritol and chitin or low-substituted hydroxypropyl methylcellulose or carboxymethyl starch sodium or crosslinked carboxymethyl fecula sodium or insoluble crospolyvinylpyrrolidone, and the weight percentage of compound disintegrating agent mesoerythrit is 30%-70%.
Claims (7)
1. blood-nourishing and brain-refreshing oral cavity disintegration tablet, effective ingredient and pharmaceutic adjuvant by following raw materials in weight portion medicine preparation are prepared from: Radix Angelicae Sinensis 300-350 part, Rhizoma Chuanxiong 300-350, Radix Paeoniae Alba 250-300, Radix Rehmanniae Preparata 250-300, Ramulus Uncariae Cum Uncis 650-700, Caulis Spatholobi 650-700, Spica Prunellae 650-700, Semen Cassiae 650-700, Concha Margaritifera 650-700, Rhizoma Corydalis 300-350, Herba Asari 60-70; It is characterized in that each composition weight portion proportioning is: effective ingredient 50-110, disintegrating agent 57-75, filler 128-167, lubricant 5-8; Disintegrating agent wherein is to contain the compound disintegrating agent that weight percentage is 30～70% erythritol.
2. the described blood-nourishing and brain-refreshing oral cavity disintegration tablet of claim 1 is characterized in that, wherein the weight portion proportioning of crude drug is:
Radix Angelicae Sinensis 338, Rhizoma Chuanxiong 338, the Radix Paeoniae Alba 270.3, Radix Rehmanniae Preparata 270.3, Ramulus Uncariae Cum Uncis 675.7, Caulis Spatholobi 675.7,
Spica Prunellae 675.7, Semen Cassiae 675.7, Concha Margaritifera 675.7, Rhizoma Corydalis 338, Herba Asari 67.3.
3. claim 1 or 2 described blood-nourishing and brain-refreshing oral cavity disintegration tablets, it is characterized in that, described compound disintegrating agent is selected from following combination: erythritol and chitin, erythritol and low-substituted hydroxypropyl methylcellulose, erythritol and carboxymethyl starch sodium, erythritol and crosslinked carboxymethyl fecula sodium, erythritol and insoluble crospolyvinylpyrrolidone.
4. claim 1 or 2 described blood-nourishing and brain-refreshing oral cavity disintegration tablets is characterized in that described filler is a microcrystalline Cellulose.
5. the described blood-nourishing and brain-refreshing oral cavity disintegration tablet of claim 4 is characterized in that, described filler is a nano micro crystal cellulose.
6. claim 1 or 2 described blood-nourishing and brain-refreshing oral cavity disintegration tablets is characterized in that, described lubricant is a kind of in magnesium stearate, Pulvis Talci, the Stepanol MG.
7. the preparation method of the arbitrary described blood-nourishing and brain-refreshing oral cavity disintegration tablet of claim 1-6 is characterized in that:
(1) takes by weighing ten Chinese medicines simply by formula ratio, put into the extraction pot of Chinese medicine dynamic extraction multifunction extracting device, add water 6-20 doubly, extract 2-5 time, each 2-5 hour, merge extractive liquid,, relative density is the extractum of 1.20-1.25 when being concentrated to 20 ℃, add the ethanol of 60%-80%, left standstill 24 hours, get supernatant, reclaim ethanol to most, vacuum concentration, drying obtains effective ingredient;
(2) effective ingredient is mixed with disintegrating agent, add filler, granulate, add lubricant, tabletting obtains the blood-nourishing and brain-refreshing oral cavity disintegration tablet.
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| CN1872217B (en) * | 2005-06-03 | 2011-10-05 | 天津天士力制药股份有限公司 | A medication for treating headache, and preparation method |
| CN1954862B (en) * | 2005-10-28 | 2012-03-28 | 天津天士力制药股份有限公司 | Syrup for treating headache |
| CN101194964B (en) * | 2006-12-08 | 2013-08-21 | 天士力制药集团股份有限公司 | Coated tablet for treating headache and method for preparing the same |
| CN101194961B (en) * | 2006-12-08 | 2013-06-05 | 天士力制药集团股份有限公司 | Aerosol for treating headache and method for preparing the same |
| CN101194945B (en) * | 2006-12-08 | 2013-06-05 | 天士力制药集团股份有限公司 | Tablet for treating headache and method for preparing the same |
| CN101194965B (en) * | 2006-12-08 | 2013-06-05 | 天士力制药集团股份有限公司 | Mastication tablet for treating headache and method for preparing the same |
| CN102133239B (en) * | 2010-01-21 | 2014-08-13 | 天士力制药集团股份有限公司 | Chinese medical concentrated pill and preparation method thereof |
| CN102998375B (en) * | 2011-09-13 | 2016-04-20 | 天士力制药集团股份有限公司 | A kind of method simultaneously detecting forulic acid and paeoniflorin content in blood-nourishing and brain-refreshing granules |
| WO2015039619A1 (en) * | 2013-09-22 | 2015-03-26 | 天士力制药集团股份有限公司 | Use of yangxueqingnao formulation in preparation of medicine for treating alzheimer's disease |
| CN105796729B (en) * | 2016-03-29 | 2020-07-14 | 黑龙江大学 | Blood-nourishing and brain-refreshing soft capsule and preparation method thereof |
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