CN1682829A - Wuji dripping pill for treating liver and stomach diseases and its preparing method - Google Patents
Wuji dripping pill for treating liver and stomach diseases and its preparing method Download PDFInfo
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- CN1682829A CN1682829A CNA2005100089020A CN200510008902A CN1682829A CN 1682829 A CN1682829 A CN 1682829A CN A2005100089020 A CNA2005100089020 A CN A2005100089020A CN 200510008902 A CN200510008902 A CN 200510008902A CN 1682829 A CN1682829 A CN 1682829A
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Abstract
The present invention relates to medicine composition for treating liver and stomach disorder, bitter taste in the mouth and gastric upset, vomiting and acid regurgitation and abdominal pain and dysentery, and is especially one kind of oral dripping pill preparation prepared based on traditional Chinese medicine recipe. It has high bioavailability, fast medicine release, fast acting, high effective component content and convenient taking. The Wuji dripping pill is prepared with berberine hydrochloride, the active components extracted from evodia and white peony root and matrix carrier.
Description
Technical field
The present invention relates to a kind of treatment incoordination between the liver and stomach, bitter taste is noisy, vomiting acid regurgitation, the pharmaceutical composition of stomachache dysentery, particularly a kind of oral drop pills that is prepared from Chinese medicine Cheng Fangwei master.
Background technology
One one of Chinese Pharmacopoeia version in 2000 P.429 page or leaf liver-fire-purging and spleen-stomach-regulating pill item is described below standard:
[prescription] Rhizoma Coptidis 300g, Fructus Evodiae (system) 50g, the Radix Paeoniae Alba (stir-fry) 300g;
[function with cure mainly] removing fire from the liver, and taste.Be used for incoordination between the liver and stomach, bitter taste is noisy, vomiting acid regurgitation, stomachache dysentery.
[usage and consumption] is oral, a 3～6g, 2 times on the one.
Under 127 pages of Zuojin Wan items of traditional Chinese medical science class teaching material " pharmacology of Chinese medical formulae " by Mr. Xie Ming chief editor, quoted the institute side of work such as Wu Qian for liver-fire-purging and spleen-stomach-regulating pill by " the positive agent of this removing fire from the liver.Liver controlled several: water declines and wood is difficult to give birth to, and Dihuang Wan second certain herbaceous plants with big flowers homology is also; Soil declines and wood is difficult to plant, and the slow liver ridging of ginseng Siberian cocklebur Radix Glycyrrhizae agent is also; The herbal classic blood deficiency has fire, relieves inflammation or internal heat with XIAOYAO POWDER; Blood deficiency is anhydrous, uses the SIWU TANG yin nourishing.As for the method for mending fire, also down with kidney; And the seem heart is then gone up in controlling of pathogenic fire purging.The private Rhizoma Coptidis of Zuojin Wan is monarch, from rushing down the method for its son actually, with the gesture of straight folding inflammation on it.Fructus Evodiae is asked mutually from class, and it is descending to draw heat, and with dry its stagnation of liver-QI of opening of suffering, punishes its skewer lattice, so think assistant.So must this QI excess and the not empty person of soil, multitudinous can be suitable.Wood is from a left side, and system from gold also.”
Also have formulas or directions put into verse: left golden yellow company and Fructus Evodiae, costalgia acid regurgitation are known and can be removed; It is own to add Radix Paeoniae name penta again, specially controls the dysentery pain at umbilicus.
As seen liver-fire-purging and spleen-stomach-regulating pill is based on treatment incoordination between the liver and stomach, stomachache dysentery, when no doubt.
Yet, the conventional Chinese medicine preparation that utilizes conventional art to obtain because of its preparation technology's characteristics, exists after taking that dissolve scattered time limit is long, dissolution is low, absorption is relatively poor, problem such as liver sausage first pass effect and bioavailability are low, thereby influence the performance of drug effect, also directly affect the effect of treatment.Moreover traditional oral preparation of Chinese traditional medicinal drug loading is low, and dose is big, and dust is big in the preparation process, sanitary condition is difficult to control, and not only inconvenient patient takes, and simultaneously easier environment is polluted, the administration of health that is unfavorable for medicine is unfavorable for that also the direct labor's is healthy.The modern existing clinically report that uses penta oneself drink, penta own capsule and add relevant penta own new formulation such as flavor penta own capsule, now draw record as follows:
1. Li Xiong is bright. and huoxiang zhengqi powder closes liver-fire-purging and spleen-stomach-regulating pill plus-minus treatment chronic superficial gastritis. practical combination of Chinese and Western medicine magazine VOL.10 in 1997, NO.13-P.1291;
2. Song Hua is as, Zhang Wenhua. add flavor liver-fire-purging and spleen-stomach-regulating pill treatment chronic diarrhea 35 examples. and practical Journal of Traditional Chinese Medicine 1995,2-P.7;
3. Liu Ya is refined, Li Rui foot, Li Wenqi. penta oneself drink treatment esophageal carcinoma postoperative cardiac carcinoma, 43 examples of suffering from diarrhoea. and the Shaanxi traditional Chinese medical science 1995,16 (1) is P.11;
4. the mound root is complete, Qiao Jin, Sun Xicai. penta own capsule for treating chronic atrophic gastritis 93 examples. and the Shaanxi traditional Chinese medical science 1994,15 (7) is P.291.
2002.8, also disclose a kind of one group of preparation that is prepared from liver-fire-purging and spleen-stomach-regulating pill Cheng Fangwei basis 28. disclosed application number is 01100867.9 Chinese patent technology " nano medicine ' Wuji ' and preparation method thereof ", wherein also comprised drop pill with nanometer characteristics.But as can be known by its claims and the disclosed technical scheme of description, this patent is except that the embodiment that has provided capsule, powder needle injection and membrane three dosage forms such as (patches), unexposed any about preparing the technical scheme of penta own drop pill, and according to the technical characterstic of drop pill, the key of its invention just be actual substrate selection, proportioning determine and concrete preparation process process conditions content such as determine.According to the disclosed content of this patent application technological document, can't not obtain penta own drop pill involved in the present invention under the condition by creative work, so the open of this patented technology should not damage to novelty of the present invention at all.
Summary of the invention
Purpose of the present invention is to remedy the deficiency of liver-fire-purging and spleen-stomach-regulating pill traditional preparation process technology, provides a kind of drug loading big, release fast, produce effects fast, bioavailability height, and the penta own drop pill of conveniently taking.Penta own drop pill involved in the present invention, no dust takes place in preparation process, can not cause any pollution.Adopt following preparation method can obtain penta own drop pill involved in the present invention.
1. berberine hydrochloride (2000 editions two ones 548 pages of Chinese Pharmacopoeias)
1.1 English name---Berberine Hydrochloride
1.2 another name---berberine (umbellatine)
1.3 chemical name-5,6-dihydro-9,10-dimethoxy phenyl [g]-1,3-benzo dioxole [5,6-a] quinolizine chlorination dihydrate
1.4 chemical structural formula
1.5 molecular formula---C
20H
18CINO
42H
2O
1.6 molecular weight---407.85
1.7 classification---antimicrobial drug
The berberine hydrochloride chemical structural formula
1.8 character---this product is a yellow crystalline powder; Nothing is smelt, and flavor is extremely bitter.This product is dissolved in hot water, slightly soluble in water or ethanol, and soluble,very slightly in chloroform, insoluble in ether;
2. the extract that contains Fructus Evodiae total alkaloids---this extract derives from the rutaceae Fructus Evodiae, can use purity higher extracted thing, also can be the thick paste that contains Fructus Evodiae total alkaloids, dried cream or dry powder, its main active pharmaceutical ingredient be to contain the Wu Fructus Evodiae
(evodiamine), the Wu Fructus Evodiae is inferior
(rutaecarpine) Yi is Ji the Hydroxyalkyl base Wu Fructus Evodiae
(hydroxy-evodiamine) Fructus Evodiae total alkaloids;
3. the extract that contains Radix Paeoniae Alba total glucosides---can be the extract that contains higher Radix Paeoniae Alba total glucosides composition, also can be the thick paste that contains Radix Paeoniae Alba total glucosides, dried cream or dry powder, its main active pharmaceutical ingredient has following five kinds: paeoniflorin, albiflorin, acetyl paeoniflorin, paeoniflorin R
1And benzoylpaeoniflorin, be referred to as the Radix Paeoniae Alba and always make glycoside;
4. substrate-Polyethylene Glycol
1500～20000, any one or two or more mixture in the pharmaceutic adjuvant such as stearic acid, sodium stearate, glycerin gelatine, polyoxyethylene stearate 40 esters, Lac, polyoxyethylene monostearate, polyethers, carboxymethyl starch sodium, sodium lauryl sulphate;
5. be unit with g or kg, according to the weight portion meter, Fructus Evodiae extract calculates with its total alkaloids, Radix Paeoniae Alba extract calculates with its total glycosides, get 1 part of Fructus Evodiae total alkaloids, the berberine hydrochloride of 20 parts of Radix Paeoniae Alba total glucosidess and 60 parts is pre-mixed the hybrid medicine raw material that even conduct contains active pharmaceutical ingredient, the hybrid medicine raw material: substrate=1: 1～1: 9;
6. according to the given ratio of prescription, accurately take by weighing drug extract and substrate, be placed on heating while stirring in the heating container, standby until the fused solution that obtains containing drug extract and substrate and/or emulsion and/or suspension;
7. adopt homemade or general drop pill machine (as the TZDW-1 type drop pill machine of Changzheng Tianmin High Science ﹠ Technology Co., Ltd., Beijing's production), and the temperature control system of adjustment drop pill machine, make the water dropper temperature heating of drop pill machine and remain on (50～90) ℃, the temperature cooling of condensing agent also remains on (40～-5) ℃;
8. when treating that the temperature of condensing agent in dropping-pill machine head and the condensation column is stable respectively and reaching desired state of temperature, fused solution and/or the emulsion and/or the suspension that will contain drug extract and substrate, place in the water dropper jar of drop pill machine, splash in the condensing agent, condensing agent can be any one in liquid paraffin, methyl-silicone oil, the vegetable oil;
9. will shrink the drop pill taking-up of molding by the outlet of drop pill machine, remove the surface condensation agent, be drying to obtain.
[appendix 1: contain the preparation of Fructus Evodiae total alkali extract]
Method 1: take by weighing the Fructus Evodiae crude drug, with 10 times of amount finite concentrations is twice of 70% alcoholic solution reflux, extract,, ethanol to the residue that reclaims in the extracting solution does not have the ethanol flavor, get the alcohol extraction part, 1% hydrochloric acid solution with capacity extracts then, extracting liquid filtering, it is about 9 that filtrate is regulated pH value with strong aqua ammonia, and the centrifugal precipitation that obtains is used chloroform extraction, the combined chloroform extracting solution, filter supernatant, with anhydrous sodium sulfate dehydration, remove by filter sodium sulfate, reclaim chloroform, residue is drying to obtain the Fructus Evodiae extract that contains Fructus Evodiae total alkaloids.
Method 2: take by weighing the Fructus Evodiae crude drug, with 70% alcohol reflux 2 times, 8 times of amounts of the 1st usefulness alcohol reflux 2h, 7 times of amounts of the 2nd usefulness alcohol reflux 1.5h.Reclaim the ethanol in the extracting solution, be concentrated into relative density and be 1.3～1.35 thick paste; Perhaps dry, pulverizing under decompression (0.1MPa), low temperature (60 ℃) condition gets extract dry powder.
Method 3: take by weighing the Fructus Evodiae crude drug, the soak with ethanol 3h with 70%, Soxhlet is extracted 4h, and ethanol to the residue that reclaims in the extracting solution does not have the ethanol flavor, is concentrated into relative density and is 1.3～1.35 thick paste; Perhaps dry, pulverizing under decompression (0.1MPa), low temperature (60 ℃) condition gets extract dry powder.
[appendix 2: contain the Radix Paeoniae Alba total glucosides preparation method of extract]
Method 1: with g or kg is unit, get an amount of Radix Paeoniae Alba, with 7 times of 80% alcohol reflux 2 times, each 2 hours, merge alcohol extract, filter, reclaim ethanol to there not being the alcohol flavor, under decompression (0.1MPa), low temperature (60 ℃) condition, be condensed into relative density and be 1.3～1.35 thick paste, or continue to make drying under the same conditions, be ground into dry powder promptly.
Method 2: with g or kg is unit, get an amount of Radix Paeoniae Alba, with 10 times of water boiling and extraction 2 times, each 1 hour, merge decocting liquid, centrifugal filtration is condensed into relative density and is 1.3～1.35 thick paste under decompression (0.1MPa), low temperature (60 ℃) condition, or continue to make drying under the same conditions, be ground into dry powder promptly.
Method 3: with g or kg is unit, gets an amount of Radix Paeoniae Alba, 7 times of 80% alcohol reflux twice, and each two hours, merge alcohol extract, filter, reclaim ethanol to not having alcohol flavor, concentrated solution 0.1mol/LNaHCO
3Transfer to PH6～6.5, with n-butanol extraction three times, combining extraction liquid, concentrating under reduced pressure, drying, the Radix Paeoniae Alba total glucosides powder.
Method 4: with g or kg is unit, gets an amount of Radix Paeoniae Alba, twice of 7 times of 80% alcohol reflux, each two hours, merge alcohol extract, filter, reclaim ethanol to there not being the alcohol flavor, add the suitable quantity of water dilution, filter, filtrate adds 20 times of amount macroporous resin column, and first water is eluted to the Molish reflection and is negative, again with the abundant eluting of 20% ethanol, collect eluent, concentrating under reduced pressure, drying gets the Radix Paeoniae Rubra total glycosides powder.
What provide above is the preparation method of several frequently seen Fructus Evodiae and Radix Paeoniae Alba extract, under the same or analogous prerequisite of main active pharmaceutical ingredient of extract, is not limited to this several method.
Beneficial effect
One one of Chinese Pharmacopoeia version in 2000 P.429 page or leaf liver-fire-purging and spleen-stomach-regulating pill item is described below standard:
[prescription] Rhizoma Coptidis 300g, Fructus Evodiae (system) 50g, the Radix Paeoniae Alba (stir-fry) 300g;
[function with cure mainly]: removing fire from the liver, and taste.Be used for incoordination between the liver and stomach, bitter taste is noisy, vomiting acid regurgitation, stomachache dysentery.
[usage and consumption] is oral, a 3～6g, 2 times on the one.
Under 127 pages of Zuojin Wan items of traditional Chinese medical science class teaching material " pharmacology of Chinese medical formulae " by Mr. Xie Ming chief editor, quoted the institute side of work such as Wu Qian for liver-fire-purging and spleen-stomach-regulating pill by " the positive agent of this removing fire from the liver.Liver controlled several: water declines and wood is difficult to give birth to, and Dihuang Wan second certain herbaceous plants with big flowers homology is also; Soil declines and wood is difficult to plant, and the slow liver ridging of ginseng Siberian cocklebur Radix Glycyrrhizae agent is also; The herbal classic blood deficiency has fire, relieves inflammation or internal heat with XIAOYAO POWDER; Blood deficiency is anhydrous, uses the SIWU TANG yin nourishing.As for the method for mending fire, also down with kidney; And the seem heart is then gone up in controlling of pathogenic fire purging.The private Rhizoma Coptidis of Zuojin Wan is monarch, from rushing down the method for its son actually, with the gesture of straight folding inflammation on it.Fructus Evodiae is asked mutually from class, and it is descending to draw heat, and with dry its stagnation of liver-QI of opening of suffering, punishes its skewer lattice, so think assistant.So must this QI excess and the not empty person of soil, multitudinous can be suitable.Wood is from a left side, and system from gold also." visible liver-fire-purging and spleen-stomach-regulating pill is based on treatment incoordination between the liver and stomach, stomachache dysentery, when no doubt.
Yet, the conventional Chinese medicine preparation that utilizes conventional art to obtain because of its preparation technology's characteristics, exists after taking that dissolve scattered time limit is long, dissolution is low, absorption is relatively poor, problem such as liver sausage first pass effect and bioavailability are low, thereby influence the performance of drug effect, also directly affect the effect of treatment.Moreover traditional oral preparation of Chinese traditional medicinal drug loading is low, and dose is big, and dust is big in the preparation process, sanitary condition is difficult to control, and not only inconvenient patient takes, and simultaneously easier environment is polluted, the administration of health that is unfavorable for medicine is unfavorable for that also the direct labor's is healthy.
Penta own drop pill involved in the present invention, utilize substrate such as surfactant polyethylene with making solid dispersion through the berberine of purifying and the extract of Fructus Evodiae, make medicine be molecule, colloid or microcrystalline state and be dispersed in the substrate, the total surface area of medicine is increased.And substrate is hydrophilic, and medicine is had wetting action, can make that medicine is rapidly molten to loose into microgranule or solution, thereby makes the dissolving of medicine and absorb and accelerate, thereby has improved bioavailability, has brought into play efficient, quick-acting effects.
Compare with traditional liver-fire-purging and spleen-stomach-regulating pill, penta own drop pill involved in the present invention has following beneficial effect:
1. the drop pill that utilizes the solid dispersion technology preparation and get has the dissolution time weak point, and the advantage that dissolution is high can adopt sublingual administration, and effective ingredient is fully contacted with mucomembranous surface, absorbs by mucomembranous epithelial cell, directly enters blood circulation.Especially sublingual administration administration contacts promptly with saliva and to dissolve rapidly, is absorbed by oral mucosa, directly enters blood circulation without gastrointestinal tract and liver, not only avoided the liver sausage first pass effect, and it is rapid to have brought into play onset, bioavailability height, the advantage that side effect is little.
The penta own drop pill that adopts embodiment provided by the present invention to obtain places clear water to make relatively gained result of dissolve scattered time limit under same room temperature condition with commercially available liver-fire-purging and spleen-stomach-regulating pill, and the whole dissolution times of commercially available liver-fire-purging and spleen-stomach-regulating pill are about 45 minutes, and the obvious sediment deposits yields is arranged; And whole dissolution times of penta own drop pill involved in the present invention only are 14 minutes, and the precipitation-free thing exists.
2. penta own drop pill production technology, equipment involved in the present invention are simple, and the cycle is short, the automaticity height, and production efficiency is also high.This left golden drop pill in addition, the medicament contg height, dose little and convenient (but sublingual administration) is particularly advantageous in and swallows inconvenient patient and take.According to China's pharmacopeia regulation, the dose of liver-fire-purging and spleen-stomach-regulating pill is a 3g～6g, 2 times on the one.And penta own drop pill involved in the present invention, the dosage of every day only is 2g.
3. this preparation is by after solid drugs and substrate heating, being melt into liquid state, splash in the not miscible condensed fluid and make, and the stability of drug height, not facile hydrolysis, oxidation is not subject to the influence of crystal formation, thereby guaranteed drug quality, increased stability.
4. penta own drop pill involved in the present invention, main production process is all carried out under liquid state, and no dust pollution helps labor protection and environmental protection.
The specific embodiment
Now with several groups of specific embodiments, be described further with regard to the preparation method of the golden drop pill in a left side of the present invention.
First group: the test of single-matrix
1. berberine hydrochloride (producing) by Zhangjagang City pharmaceutical factory
1.1 another name---berberine (umbellatine)
1.2 chemical name-5,6-dihydro-9,10-dimethoxy phenyl [g]-1,3-benzo dioxole [5,6-a] quinolizine chlorination dihydrate
2. the Fructus Evodiae extract that contains Fructus Evodiae total alkaloids---adopt method preparation that appendix 1 provides and the extract dry powder that contains Fructus Evodiae total alkaloids;
3. substrate---Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), a kind of in pharmaceutically suitable carrier such as polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac;
4. be unit with g or kg, by weight:
4.1 berberine hydrochloride: the extract of Fructus Evodiae (calculating)=60: 1 with Fructus Evodiae total alkaloids
(4.2 the extract of berberine hydrochloride+Fructus Evodiae): substrate=1: 1～1: 9
5. the process that provides according to [preparation method] 5～8 is prepared, and can obtain the left golden drop pill of different size.
[result of the test]
Test 1: for observe berberine hydrochloride, Fructus Evodiae extract and different substrates when 1: 1 the proportioning prepared Zuojin Wan in qualitative difference, according to 1: 1 ratio, with berberine hydrochloride, Fructus Evodiae extract respectively with Polyethylene Glycol
2000, Polyethylene Glycol
4000, Polyethylene Glycol
6000, Polyethylene Glycol
8000, Polyethylene Glycol
10000, Polyethylene Glycol
20000, pharmaceutically suitable carrier such as polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac matches, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain 15 pharmaceutical compositions experiments that contain berberine hydrochloride, Fructus Evodiae extract and different substrates, and obtain 15 groups of different experimental results and see Table 1.
Test 2: for observe berberine hydrochloride, Fructus Evodiae extract and different substrates when 1: 3 the proportioning prepared Zuojin Wan in qualitative difference, according to 1: 3 ratio, with berberine hydrochloride, Fructus Evodiae extract respectively with Polyethylene Glycol
2000, Polyethylene Glycol
4000, Polyethylene Glycol
6000, Polyethylene Glycol
8000, Polyethylene Glycol
10000, Polyethylene Glycol
20000, pharmaceutically suitable carrier such as polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac matches, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain 15 pharmaceutical compositions experiments that contain berberine hydrochloride, Fructus Evodiae extract and different substrates, and obtain 15 groups of different experimental results and see Table 2.
Test 3: for observe berberine hydrochloride, Fructus Evodiae extract and different substrates when 1: 9 the proportioning prepared Zuojin Wan in qualitative difference, according to 1: 9 ratio, with berberine hydrochloride, Fructus Evodiae extract respectively with Polyethylene Glycol
2000, Polyethylene Glycol
4000, Polyethylene Glycol
6000, Polyethylene Glycol
8000, Polyethylene Glycol
10000, Polyethylene Glycol
20000, pharmaceutically suitable carrier such as polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac matches, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain 15 pharmaceutical compositions experiments that contain berberine hydrochloride, Fructus Evodiae extract and different substrates, and obtain 15 groups of different experimental results and see Table 3.
Second group: the test of mixed-matrix
1. berberine hydrochloride (producing) by Zhangjagang City pharmaceutical factory
1.1 another name---berberine (umbellatine)
1.2 chemical name---5,6-dihydro-9,10-dimethoxy phenyl [g]-1,3-benzo dioxole [5,6-a] quinolizine chlorination dihydrate
2. the Fructus Evodiae extract that contains Fructus Evodiae total alkaloids---adopt method preparation that appendix 1 provides and the extract dry powder that contains Fructus Evodiae total alkaloids;
3. substrate:
3.1 Polyethylene Glycol---English name Macrogol,
3.2 polyoxyethylene stearate 40 esters---English name Polyoxyl (40) Stearate,
Molecular formula is with C
17H
35COO (CH
2CH
2O)
nH represents that n is about 40,
3.3 poloxamer---English name Poloxamer, polyoxyethylene poly-oxygen propylene aether, molecular formula HO (C
2H
4O)
a(C
3H
6O)
b(C
2H
4O)
cH,
The sodium salt of the starch carboxymethyl ester that 3.4 carboxymethyl starch sodium---English name Carboxymethylstach Sodium, starch generates with the monoxone effect under alkali condition,
3.5 betacyclodextrin---English name Betacyclodextrin, molecular formula C
6H
10O
5, this product is that ring dextrin glucosyl transferase acts on 7 glucoses that starch generates with α-1, the bonded cyclic oligosaccharide of 4-glycosidic bond;
4. be unit with g or kg, by weight:
4.1 berberine hydrochloride: the extract of Fructus Evodiae (calculating)=60: 1 with Fructus Evodiae total alkaloids
(4.2 the extract of berberine hydrochloride+Fructus Evodiae): substrate=1: 1～1: 9
5. the process that provides according to [preparation method] 5～8 is prepared, and can obtain the left golden drop pill of different size.
[result of the test]
Test 4: in order to observe berberine hydrochloride, the mass discrepancy of Fructus Evodiae extract and the mixed-matrix golden drop pill in a prepared left side when 1: 1 proportioning, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 1 mixed evenly as mixed-matrix, again according to 1: 1 ratio with berberine hydrochloride, different with the 4 kinds respectively mixing matrix phases of Fructus Evodiae extract mix and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain 4 berberine hydrochloride, the experiment of pharmaceutical composition that Fructus Evodiae extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 4.
Test 5: in order to observe berberine hydrochloride, the mass discrepancy of Fructus Evodiae extract and the mixed-matrix golden drop pill in a prepared left side when 1: 3 proportioning, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 1 mixed evenly as mixed-matrix, again according to 1: 3 ratio with berberine hydrochloride, different with the 4 kinds respectively mixing matrix phases of Fructus Evodiae extract mix and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain 4 berberine hydrochloride, the experiment of pharmaceutical composition that Fructus Evodiae extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 5.
Test 6: in order to observe berberine hydrochloride, the mass discrepancy of Fructus Evodiae extract and the mixed-matrix golden drop pill in a prepared left side when 1: 9 proportioning, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 1 mixed evenly as mixed-matrix, again according to 1: 9 ratio with berberine hydrochloride, different with the 4 kinds respectively mixing matrix phases of Fructus Evodiae extract mix and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain 4 berberine hydrochloride, the experiment of pharmaceutical composition that Fructus Evodiae extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 6.
Test 7: in order to observe berberine hydrochloride, the mass discrepancy of Fructus Evodiae extract and the mixed-matrix golden drop pill in a prepared left side when 1: 1 proportioning, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 5 mixed evenly as mixed-matrix, again according to 1: 1 ratio with berberine hydrochloride, different with the 4 kinds respectively mixing matrix phases of Fructus Evodiae extract mix and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain 4 berberine hydrochloride, the experiment of pharmaceutical composition that Fructus Evodiae extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 7.
Test 8: in order to observe berberine hydrochloride, the mass discrepancy of Fructus Evodiae extract and the mixed-matrix golden drop pill in a prepared left side when 1: 3 proportioning, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 5 mixed evenly as mixed-matrix, again according to 1: 3 ratio with berberine hydrochloride, different with the 4 kinds respectively mixing matrix phases of Fructus Evodiae extract mix and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain 4 berberine hydrochloride, the experiment of pharmaceutical composition that Fructus Evodiae extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 8.
Test 9: in order to observe berberine hydrochloride, the mass discrepancy of Fructus Evodiae extract and the mixed-matrix golden drop pill in a prepared left side when 1: 9 proportioning, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 5 mixed evenly as mixed-matrix, again according to 1: 9 ratio with berberine hydrochloride, different with the 4 kinds respectively mixing matrix phases of Fructus Evodiae extract mix and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain 4 berberine hydrochloride, the experiment of pharmaceutical composition that Fructus Evodiae extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 9.
Test 10: in order to observe berberine hydrochloride, the mass discrepancy of Fructus Evodiae extract and the mixed-matrix golden drop pill in a prepared left side when 1: 1 proportioning, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 10 mixed evenly as mixed-matrix, again according to 1: 1 ratio with berberine hydrochloride, different with the 4 kinds respectively mixing matrix phases of Fructus Evodiae extract mix and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain 4 berberine hydrochloride, the experiment of pharmaceutical composition that Fructus Evodiae extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 10.
Test 11: in order to observe berberine hydrochloride, the mass discrepancy of Fructus Evodiae extract and the mixed-matrix golden drop pill in a prepared left side when 1: 3 proportioning, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 10 mixed evenly as mixed-matrix, again according to 1: 3 ratio with berberine hydrochloride, different with the 4 kinds respectively mixing matrix phases of Fructus Evodiae extract mix and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain 4 berberine hydrochloride, the experiment of pharmaceutical composition that Fructus Evodiae extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 11.
Test 12: in order to observe berberine hydrochloride, the mass discrepancy of Fructus Evodiae extract and the mixed-matrix golden drop pill in a prepared left side when 1: 9 proportioning, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 12 mixed evenly as mixed-matrix, again according to 1: 9 ratio with berberine hydrochloride, different with the 4 kinds respectively mixing matrix phases of Fructus Evodiae extract mix and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain 4 berberine hydrochloride, the experiment of pharmaceutical composition that Fructus Evodiae extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 12.
The group practices of table 1 drug extract and single-matrix
(drug extract: substrate=1: 1)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyethylene Glycol 2000 | ?????50.0 | ????60 | ????＜30 | ????＞10 | + |
| Polyethylene Glycol 4000 | ?????50.0 | ????76 | ????＜30 | ????＞10 | + |
| Polyethylene Glycol 6000 | ?????50.0 | ????76 | ????＜30 | ????＞10 | ++ |
| Polyethylene Glycol 8000 | ?????50.0 | ????75 | ????＜30 | ????＞10 | ++ |
| Polyethylene Glycol 10000 | ?????50.0 | ????78 | ????＜30 | ????＞10 | ++ |
| Polyethylene Glycol 20000 | ?????50.0 | ????80 | ????＜30 | ????＞10 | ++ |
| Polyoxyethylene stearate 40 esters | ?????50.0 | ????75 | ????＜30 | ????＞10 | ++ |
| Betacyclodextrin | ?????50.0 | ????68 | ????＜30 | ????＞10 | + |
| Poloxamer | ?????50.0 | ????75 | ????＜30 | ????＞10 | ++ |
| Carboxymethyl starch sodium | ?????50.0 | ????73 | ????＜30 | ????＞10 | + |
| Sodium lauryl sulphate | ?????50.0 | ????66 | ????＞30 | ????＞10 | ++ |
| Stearic acid | ?????50.0 | ????54 | ????＞30 | ????＞10 | ++ |
| Sodium stearate | ?????50.0 | ????54 | ????＞30 | ????＞10 | ++ |
| Glycerin gelatine | ?????50.0 | ????53 | ????＞30 | ????＞10 | + |
| Lac | ?????50.0 | ????52 | ????＞30 | ????＞10 | + |
The group practices of table 2 drug extract and single-matrix
(drug extract: substrate=1: 3)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyethylene Glycol 2000 | ????25.0 | ????79 | ????＜30 | ????＞10 | ++ |
| Polyethylene Glycol 4000 | ????25.0 | ????86 | ????＜30 | ????＜10 | +++ |
| Polyethylene Glycol 6000 | ????25.0 | ????91 | ????＜30 | ????＜10 | +++ |
| Polyethylene Glycol 8000 | ????25.0 | ????91 | ????＜30 | ????＜10 | +++ |
| Polyethylene Glycol 10000 | ????25.0 | ????92 | ????＜30 | ????＜10 | +++ |
| Polyethylene Glycol 20000 | ????25.0 | ????92 | ????＜30 | ????＜10 | +++ |
| Polyoxyethylene stearate 40 esters | ????25.0 | ????93 | ????＜30 | ????＜10 | ++ |
| Betacyclodextrin | ????25.0 | ????83 | ????＜30 | ????＞10 | ++ |
| Poloxamer | ????25.0 | ????91 | ????＜30 | ????＜10 | +++ |
| Carboxymethyl starch sodium | ????25.0 | ????86 | ????＜30 | ????＜10 | +++ |
| Sodium lauryl sulphate | ????25.0 | ????77 | ????＜30 | ????＞10 | ++ |
| Stearic acid | ????25.0 | ????73 | ????＞30 | ????＞10 | +++ |
| Sodium stearate | ????25.0 | ????71 | ????＞30 | ????＞10 | +++ |
| Glycerin gelatine | ????25.0 | ????70 | ????＞30 | ????＞10 | +++ |
| Lac | ????25.0 | ????70 | ????＞30 | ????＞10 | +++ |
The group practices of table 3 drug extract and single-matrix
(drug extract: substrate=1: 9)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyethylene Glycol 2000 | ????10.0 | ????80 | ????＜30 | ????＞10 | ++ |
| Polyethylene Glycol 4000 | ????10.0 | ????86 | ????＜30 | ????＜10 | +++ |
| Polyethylene Glycol 6000 | ????10.0 | ????90 | ????＜30 | ????＜10 | +++ |
| Polyethylene Glycol 8000 | ????10.0 | ????90 | ????＜30 | ????＜10 | +++ |
| Polyethylene Glycol 10000 | ????10.0 | ????92 | ????＜30 | ????＜10 | +++ |
| Polyethylene Glycol 20000 | ????10.0 | ????93 | ????＜30 | ????＜10 | +++ |
| Polyoxyethylene stearate 40 esters | ????10.0 | ????92 | ????＜30 | ????＜10 | ++ |
| Betacyclodextrin | ????10.0 | ????81 | ????＜30 | ????＞10 | ++ |
| Poloxamer | ????10.0 | ????90 | ????＜30 | ????＜10 | +++ |
| Carboxymethyl starch sodium | ????10.0 | ????87 | ????＜30 | ????＜10 | +++ |
| Sodium lauryl sulphate | ????10.0 | ????79 | ????＜30 | ????＞10 | +++ |
| Stearic acid | ????10.0 | ????76 | ????＞30 | ????＞10 | +++ |
| Sodium stearate | ????10.0 | ????75 | ????＞30 | ????＞10 | +++ |
| Glycerin gelatine | ????10.0 | ????72 | ????＞30 | ????＞10 | +++ |
| Lac | ????10.0 | ????72 | ????＞30 | ????＞10 | +++ |
The group practices of table 4 drug extract and mixed-matrix
(drug extract: mixed-matrix=1: 1)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 1 | ????50 | ????84 | ????＜30 | ????＞10 | ++ |
| Poloxamer: Polyethylene Glycol=1: 1 | ????50 | ????82 | ????＜30 | ????＞10 | ++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | ????50 | ????79 | ????＜30 | ????＞10 | ++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | ????50 | ????72 | ????＜30 | ????＞10 | + |
The group practices of table 5 drug extract and mixed-matrix
(drug extract: mixed-matrix=1: 3)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 1 | ????25 | ????88 | ????＜30 | ????＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 1 | ????25 | ????89 | ????＜30 | ????＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | ????25 | ????86 | ????＜30 | ????＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | ????25 | ????82 | ????＜30 | ????＞10 | ++ |
The group practices of table 6 drug extract and mixed-matrix
(drug extract: mixed-matrix=1: 9)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 1 | ????10 | ????88 | ????＜30 | ????＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 1 | ????10 | ????86 | ????＜30 | ????＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | ????10 | ????83 | ????＜30 | ????＞10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | ????10 | ????80 | ????＜30 | ????＞10 | +++ |
The group practices of table 7 drug extract and mixed-matrix
(drug extract: mixed-matrix=1: 1)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 5 | ????50 | ????91 | ????＜30 | ????＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 5 | ????50 | ????90 | ????＜30 | ????＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 5 | ????50 | ????90 | ????＜30 | ????＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | ????50 | ????86 | ????＜30 | ????＜10 | ++ |
The group practices of table 8 drug extract and mixed-matrix
(drug extract: mixed-matrix=1: 3)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 5 | ????25 | ????93 | ????＜30 | ????＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 5 | ????25 | ????93 | ????＜30 | ????＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 5 | ????25 | ????91 | ????＜30 | ????＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | ????25 | ????88 | ????＜30 | ????＜10 | +++ |
The group practices of table 9 drug extract and mixed-matrix
(drug extract: mixed-matrix=1: 9)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 5 | ????10 | ????93 | ????＜30 | ????＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 5 | ????10 | ????92 | ????＜30 | ????＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 5 | ????10 | ????92 | ????＜30 | ????＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | ????10 | ????89 | ????＜30 | ????＜10 | +++ |
The group practices of table 10 drug extract and mixed-matrix
(drug extract: mixed-matrix=1: 1)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 10 | ????50 | ????92 | ????＜30 | ????＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 10 | ????50 | ????91 | ????＜30 | ????＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 10 | ????50 | ????87 | ????＜30 | ????＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 10 | ????50 | ????84 | ????＜30 | ????＞10 | +++ |
The group practices of table 11 drug extract and mixed-matrix
(drug extract: mixed-matrix=1: 3)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 10 | ????25 | ????92 | ????＜30 | ????＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 10 | ????25 | ????92 | ????＜30 | ????＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 10 | ????25 | ????89 | ????＜30 | ????＜10 | ?+++ |
| Betacyclodextrin: Polyethylene Glycol=1: 10 | ????25 | ????87 | ????＜30 | ????＜10 | +++ |
The group practices of table 12 drug extract and mixed-matrix
(drug extract: mixed-matrix=1: 9)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 10 | ????10 | ????91 | ????＜30 | ????＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 10 | ????10 | ????92 | ????＜30 | ????＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 10 | ????10 | ????91 | ????＜30 | ????＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 10 | ????10 | ????91 | ????＜30 | ????＜10 | +++ |
1. can be seen by the result in the table: when the ratio of drug extract and substrate was 1: 1, its rounding rate, the ball method of double differences was different and index such as hardness is all undesirable, and dissolve scattered time limit influenced not obvious.
2. when the ratio of drug extract and substrate is 1: 3, the rounding rate, the ball method of double differences is different and index such as hardness slightly all begins to enter preferable state.
3. when the ratio of drug extract and substrate is 1: 9, the rounding rate, the ball method of double differences is different and index such as hardness improves not obvious.
4. the general effect of composite interstitial substance is better than single-matrix.
5. the hardness method for expressing in the subordinate list adopts drop pill is placed on the glass plate, press...withes one's finger it, observes its metamorphosis."+" expression flicking promptly is out of shape, " ++ " expression distortion of firmly pressing, and " +++" expression is indeformable by it.
Attached: partial reference data questions record
Weis ten thousand woods. spironolactone treatment congestive heart failure new mechanism is inquired into. practical geriatrics 2001,15-1P.44-45
2. Guo Jiang is grand, Shen Jianhong. and captopril is united light, the moderate hypertension observation of curative effect of low dose of spironolactone treatment constitutional. and China is comprehensive clinical 2002, and 6-18 (6) is P.515-516
Claims (11)
1. one kind is used for the treatment of incoordination between the liver and stomach, bitter taste is noisy, the vomiting acid regurgitation, the drug composition oral preparation penta own drop pill of stomachache dysentery, with berberine hydrochloride, the Fructus Evodiae extract that contains the Fructus Evodiae total alkali, the Radix Paeoniae Alba extract that contains Radix Paeoniae Alba total glucosides is active pharmaceutical ingredient, be prepared from pharmaceutically suitable carrier as substrate, wherein:
1.1 berberine hydrochloride---English name Berberine Hydrochloride, another name berberine umbellatine, chemical name 5,6-dihydro-9,10-dimethoxy phenyl [g]-1,3-benzo dioxole [5,6-α] quinolizine chlorination dihydrate, molecular formula C
20H
18CINO
42H
2O;
1.2 contain the extract of Fructus Evodiae total alkaloids---this extract derives from the rutaceae Fructus Evodiae, can use purity higher extracted thing, also can be the thick paste that contains Fructus Evodiae total alkaloids, dried cream or dry powder, its main active pharmaceutical ingredient be to contain Wu Zhu Yu Alkaline (evodiamine), Wu Fructus Evodiae Ci Alkaline (rutaecarpine) Yi is Ji the Fructus Evodiae total alkaloids of Hydroxyalkyl base Wu Zhu Yu Alkaline (hydroxy-evodiamine);
1.3 contain the extract of Radix Paeoniae Alba total glucosides---can be the extract that contains higher Radix Paeoniae Alba total glucosides composition, also can be the thick paste that contains Radix Paeoniae Alba total glucosides, dried cream or dry powder, its main active pharmaceutical ingredient has following five kinds: paeoniflorin, albiflorin, acetyl paeoniflorin, paeoniflorin R
1And benzoylpaeoniflorin, be referred to as the Radix Paeoniae Alba and always make glycoside;
1.4 substrate---Polyethylene Glycol
(2000～20000), polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac, the mixture of wherein one or more;
1.5 with g or kg is unit, according to the weight portion meter, Fructus Evodiae extract calculates with its total alkaloids, Radix Paeoniae Alba extract calculates with its total glycosides, get 1 part of Fructus Evodiae total alkaloids, the berberine hydrochloride of 20 parts of Radix Paeoniae Alba total glucosidess and 60 parts is pre-mixed the hybrid medicine raw material that even conduct contains active pharmaceutical ingredient, the hybrid medicine raw material: substrate=1: 1～1: 9.
2. as claimed in claim 1 penta own drop pill, it is characterized in that the described extract that contains Fructus Evodiae total alkaloids is made by following method: it is an amount of to take by weighing Fructus Evodiae, with 10 times of amount finite concentrations is twice of 70% alcoholic solution reflux, extract,, ethanol to the residue that reclaims in the extracting solution does not have the ethanol flavor, get the alcohol extraction part, 1% hydrochloric acid solution with capacity extracts then, extracting liquid filtering, and it is about 9 that filtrate is regulated pH value with strong aqua ammonia, the centrifugal precipitation that obtains, use chloroform extraction, the combined chloroform extracting solution, filter supernatant, with anhydrous sodium sulfate dehydration, remove by filter sodium sulfate, reclaim chloroform, residue is drying to obtain the Fructus Evodiae extract that contains Fructus Evodiae total alkaloids.
3. as claimed in claim 1 penta own drop pill, it is characterized in that the described extract that contains Fructus Evodiae total alkaloids is made by following method: it is an amount of to take by weighing Fructus Evodiae, with 70% alcohol reflux 2 times, 8 times of amounts of the 1st usefulness alcohol reflux 2 hours, 7 times of amounts of the 2nd usefulness alcohol reflux 1.5 hours, reclaim the ethanol in the extracting solution, be concentrated into relative density and be 1.3～1.35 thick paste; Perhaps dry, pulverizing under decompression (0.1MPa), low temperature (60 ℃) condition gets extract dry powder.
4. as claimed in claim 1 penta own drop pill, it is characterized in that the described extract that contains Fructus Evodiae total alkaloids is made by following method: take by weighing the Fructus Evodiae crude drug, soak with ethanol with 70% 3 hours, Soxhlet was extracted 4 hours, ethanol to the residue that reclaims in the extracting solution does not have the ethanol flavor, is concentrated into relative density and is 1.3～1.35 thick paste; Perhaps dry, pulverizing under decompression (0.1MPa), low temperature (60 ℃) condition gets extract dry powder.
5. as claimed in claim 1 penta own drop pill, it is characterized in that the described extract that contains Radix Paeoniae Alba total glucosides is made by following method: with g or kg is unit, get an amount of Radix Paeoniae Alba, with 7 times of 80% alcohol reflux 2 times, each 2 hours, merge alcohol extract, filter, reclaim ethanol, under decompression (0.1MPa), low temperature (60 ℃) condition, be condensed into relative density and be 1.3～1.35 thick paste to there not being the alcohol flavor, or continue to make drying under the same conditions, be ground into dry powder promptly.
6. as claimed in claim 1 penta own drop pill, it is characterized in that the described extract that contains Radix Paeoniae Alba total glucosides is made by following method: with g or kg is unit, get an amount of Radix Paeoniae Alba, with 10 times of water boiling and extraction 2 times, each 1 hour, merge decocting liquid, centrifugal filtration, under decompression (0.1MPa), low temperature (60 ℃) condition, be condensed into relative density and be 1.3～1.35 thick paste, or continue to make drying under the same conditions, be ground into dry powder promptly.
7. as claimed in claim 1 penta own drop pill, it is characterized in that the described extract that contains Radix Paeoniae Alba total glucosides is made by following method: with g or kg is unit, get an amount of Radix Paeoniae Alba, twice of 7 times of 80% alcohol reflux, each two hours, merge alcohol extract, filter, reclaim ethanol to not having alcohol flavor, concentrated solution 0.1mol/LNaHCO
3Transfer to PH6～6.5, with n-butanol extraction three times, combining extraction liquid, concentrating under reduced pressure, drying, the Radix Paeoniae Alba total glucosides powder.
8. be unit with g or kg, get an amount of Radix Paeoniae Alba, twice of 7 times of 80% alcohol reflux, each two hours, merge alcohol extract, filter, reclaim ethanol to there not being the alcohol flavor, add the suitable quantity of water dilution, filter, filtrate adds 20 times of amount macroporous resin column, and first water is eluted to the Molish reflection and is negative, again with the abundant eluting of 20% ethanol, collect eluent, concentrating under reduced pressure, drying gets the Radix Paeoniae Rubra total glycosides powder.
9. as claimed in claim 1 penta own drop pill is characterized in that: described substrate is the mixture of Polyethylene Glycol and polyoxyethylene stearate 40 esters or Polyethylene Glycol and poloxamer or Polyethylene Glycol and carboxymethyl starch sodium or Polyethylene Glycol and betacyclodextrin; With g or kg is unit, and by weight, its mixed proportion is polyoxyethylene stearate 40 esters: Polyethylene Glycol or poloxamer: Polyethylene Glycol or carboxymethyl starch sodium: Polyethylene Glycol or betacyclodextrin: Polyethylene Glycol=1: 1～1: 10.
10. the preparation method of an own drop pill is characterized in that being made of following technical process:
10.1 berberine hydrochloride---English name Berberine Hydrochloride, another name berberine umbellatine, chemical name 5,6-dihydro-9,10-dimethoxy phenyl [g]-1,3-benzo dioxole [5,6-α] quinolizine chlorination dihydrate, molecular formula C
20H
18CINO
42H
2O;
10.2 contain the extract of Fructus Evodiae total alkaloids---this extract derives from the rutaceae Fructus Evodiae, can use purity higher extracted thing, also can be the thick paste that contains Fructus Evodiae total alkaloids, dried cream or dry powder, its main active pharmaceutical ingredient be to contain Wu Zhu Yu Alkaline (evodiamine), Wu Fructus Evodiae Ci Alkaline (rutaecarpine) Yi is Ji the Fructus Evodiae total alkaloids of Hydroxyalkyl base Wu Zhu Yu Alkaline (hydroxy-evodiamine);
10.3 contain the extract of Radix Paeoniae Alba total glucosides---can be the extract that contains higher Radix Paeoniae Alba total glucosides composition, also can be the thick paste that contains Radix Paeoniae Alba total glucosides, dried cream or dry powder, its main active pharmaceutical ingredient has following five kinds: paeoniflorin, albiflorin, acetyl paeoniflorin, paeoniflorin R
1And benzoylpaeoniflorin, be referred to as the Radix Paeoniae Alba and always make glycoside;
10.4 substrate---Polyethylene Glycol
(2000～20000), polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac, the mixture of wherein one or more;
10.5 with g or kg is unit, according to the weight portion meter, Fructus Evodiae extract calculates with its total alkaloids, Radix Paeoniae Alba extract calculates with its total glycosides, get 1 part of Fructus Evodiae total alkaloids, the berberine hydrochloride of 20 parts of Radix Paeoniae Alba total glucosidess and 60 parts is pre-mixed the hybrid medicine raw material that even conduct contains active pharmaceutical ingredient, the hybrid medicine raw material: substrate=1: 1～1: 9.
10.6, accurately take by weighing drug extract and substrate according to the given ratio of prescription, be placed on heating while stirring in the heating container, standby until the fused solution that obtains containing drug extract and substrate and/or emulsion and/or suspension;
10.7 adopt homemade or general drop pill machine, TZDW-1 type drop pill machine as Changzheng Tianmin High Science ﹠ Technology Co., Ltd., Beijing's production, and the temperature control system of adjustment drop pill machine, make the water dropper temperature heating of drop pill machine and remain on (50～90) ℃, the temperature cooling of condensing agent also remains on (40～-5) ℃;
10.8 when treating that the temperature of condensing agent in dropping-pill machine head and the condensation column is stable respectively and reaching desired state of temperature, fused solution and/or the emulsion and/or the suspension that will contain drug extract and substrate, place in the water dropper jar of drop pill machine, splash in the condensing agent, shrink molding promptly.
11. the preparation method of a kind of penta own drop pill as claimed in claim 10 is characterized in that: described condensing agent is any one or the two or more mixture in liquid paraffin, methyl-silicone oil, the vegetable oil.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100089020A CN1332651C (en) | 2005-02-24 | 2005-02-24 | Wuji dripping pill for treating liver and stomach diseases and its preparing method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100089020A CN1332651C (en) | 2005-02-24 | 2005-02-24 | Wuji dripping pill for treating liver and stomach diseases and its preparing method |
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| Publication Number | Publication Date |
|---|---|
| CN1682829A true CN1682829A (en) | 2005-10-19 |
| CN1332651C CN1332651C (en) | 2007-08-22 |
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|---|---|---|---|
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| CN (1) | CN1332651C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101874890A (en) * | 2010-04-23 | 2010-11-03 | 泰一和浦（北京）中医药研究院有限公司 | Chinese medicinal composition for treating epigastric upset and preparation method thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1202816C (en) * | 2002-02-07 | 2005-05-25 | 王志刚 | Glimepiride dripping pills |
| CN1546027A (en) * | 2003-12-02 | 2004-11-17 | 北京正大绿洲医药科技有限公司 | Dripping pills for treating allergic disease and its preparation process |
| CN1256954C (en) * | 2003-12-12 | 2006-05-24 | 北京科信必成医药科技发展有限公司 | Blumea oil dripping pills and its preparation process |
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2005
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101874890A (en) * | 2010-04-23 | 2010-11-03 | 泰一和浦（北京）中医药研究院有限公司 | Chinese medicinal composition for treating epigastric upset and preparation method thereof |
| CN101874890B (en) * | 2010-04-23 | 2011-12-28 | 泰一和浦（北京）中医药研究院有限公司 | Chinese medicinal composition for treating epigastric upset and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1332651C (en) | 2007-08-22 |
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