CN1307975C - Safflower drop pills and preparation method thereof - Google Patents
Safflower drop pills and preparation method thereof Download PDFInfo
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- CN1307975C CN1307975C CNB2004100963265A CN200410096326A CN1307975C CN 1307975 C CN1307975 C CN 1307975C CN B2004100963265 A CNB2004100963265 A CN B2004100963265A CN 200410096326 A CN200410096326 A CN 200410096326A CN 1307975 C CN1307975 C CN 1307975C
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- polyethylene glycol
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- 238000002360 preparation method Methods 0.000 title claims abstract description 34
- 244000020518 Carthamus tinctorius Species 0.000 title claims abstract description 33
- 235000003255 Carthamus tinctorius Nutrition 0.000 title claims abstract description 33
- 239000003814 drug Substances 0.000 claims abstract description 121
- 239000000203 mixture Substances 0.000 claims abstract description 15
- 208000026106 cerebrovascular disease Diseases 0.000 claims abstract 3
- 229940079593 drug Drugs 0.000 claims description 87
- 239000002202 Polyethylene glycol Substances 0.000 claims description 83
- 229920001223 polyethylene glycol Polymers 0.000 claims description 83
- 239000000284 extract Substances 0.000 claims description 81
- 239000000758 substrate Substances 0.000 claims description 39
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- 235000019698 starch Nutrition 0.000 claims description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 30
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 30
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- 241000628997 Flos Species 0.000 claims description 23
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 9
- 239000001828 Gelatine Substances 0.000 description 8
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 8
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- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 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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- DYQVDISPPLTLLR-HJQYTNQXSA-N Carthamin Natural products CC[C@H]1O[C@H]([C@H](O)[C@@H](O)[C@@H]1O)[C@]2(O)C(=C(C=C/3C(=O)C(=C(O)[C@](O)([C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)C3=O)C(=O)C=Cc5ccc(O)cc5)C(=O)C(=C2O)C(=O)C=Cc6ccc(O)cc6)O DYQVDISPPLTLLR-HJQYTNQXSA-N 0.000 description 1
- 241000208809 Carthamus Species 0.000 description 1
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
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- AZQWKYJCGOJGHM-UHFFFAOYSA-N para-benzoquinone Natural products O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The present invention discloses a medicine composition which has the functions of promoting blood circulation and removing blood stasis and is used for treating occlusive cerebrovascular disease, coronary heart disease, angitis, etc. In order to compensating the defects of the existing oral medicine preparation for treating occlusive cerebrovascular disease, coronary heart disease, angitis, etc., the aim of the present invention is to provide a safflower drop pill which has the advantages of high biologic utilization rate, rapid medicine release, rapid marked effect, little toxic or side effect, high medicine content, low administration dosage, accurate administration dosage, convenient administration, low cost and convenient outing carrying and is a medicine composition oral preparation. The safflower drop pill of the present invention is prepared by combining the extraction technology of safflower injection as a Chinese medicine patent formula with the preparation technology of the drop pill.
Description
Technical field
The present invention relates to a kind of function of promoting blood circulation to disperse blood clots that has, be used for the treatment of obliterated cerebral vascular disease, coronary heart disease, the pharmaceutical composition of diseases such as vasculitis particularly based on the prescription of Chinese traditional patent formulation Flos Carthami injection, is changed a social system a kind of oral formulations that forms through dosage form.
Background technology
Flos Carthami is Compositae 1 year or 2 years these plants of SHENGCAO, contains carthamin, Flos Carthami quinone glycoside and neocarthamin etc., and the effect of promoting blood circulation to restore menstrual flow, stasis-dispelling and pain-killing is arranged.According to the drug standard WS promulgated by the ministries or commissions of the Central Government of country
3The Flos Carthami injection that prescription that provides among-the B-3825-98 and extraction process are prepared from, main active ingredient is Carthamus yellow and flavone compound, it is a kind of obliterated cerebral vascular disease that is used for the treatment of, coronary heart disease, the pure Chinese medicine of diseases such as vasculitis is through clinical verification for many years, steady quality, determined curative effect is the common drug that is used for the treatment of above-mentioned disease clinically.
Below be drug standard WS
3Prescription that provides among-the B-3825-98 and extraction process:
Prescription: Flos Carthami 500g;
Method for making: get Flos Carthami 500g, decoct with water three times, 1 hour for the first time, 50 minutes for the second time, 30 minutes for the third time, collecting decoction, filter, filtrate is concentrated into relative density 1.16～1.26, adds ethanol and makes and contain the alcohol amount and reach 70%, cold preservation was left standstill 48 hours, filtered, filtrate recycling ethanol, and to be concentrated into relative density be 1.10～1.14 adds ethanol again and makes and contain the alcohol amount and reach 80%, cold 48 hours, filter, filtrate recycling ethanol and to be concentrated into relative density be 1.16～1.20 adds 10 times of water gagings, cold preservation, left standstill 16～24 hours, and filtered, it is 1.02～1.04 that filtrate is concentrated into relative density, regulate pH value to 7.5～8.0 with 50% sodium hydroxide solution, make into 1000ml with water for injection, filter embedding, sterilization, promptly.
Be explained as follows for this product in the appended Flos Carthami injection description:
Nomenclature of drug: Flos Carthami injection;
Main component: Flos Carthami;
Character: this product is that yellowish red color is to henna clear liquid;
Function cures mainly: blood circulation promoting and blood stasis dispelling.Be used for the treatment of obliterated cerebral vascular disease, coronary heart disease, vasculitis;
Usage and dosage:
1. treatment obliterated cerebral vascular disease intravenous drip, a 15ml (0.75) uses 1 time on the one with 10% glucose injection, 250～500ml dilution back.15～20 times is a course of treatment.
2. treatment coronary heart disease intravenous drip, a 5～20ml (0.25～1) uses 1 time on the one with 5%～10% glucose injection, 250～500ml dilution back.10～14 times is a course of treatment, is spaced apart 7～10 the course of treatment.
3. treatment vasculitis intramuscular injection, a 2.5～5ml (0.125～0.25), 1～2 time on the one;
Taboo: this product is had anaphylaxis or serious adverse reaction medical history person forbidding.This product energy promoting blood circulation to restore menstrual flow, anemia of pregnant woman and menorrhagia person's forbidding;
Points for attention:
(1) this product should not be mixed use with other medicines in same container.
(2) this product is a pure Chinese medicinal preparation, and preserving improperly may influence product quality.
Can not use when (3) finding phenomenon such as medicinal liquid becomes turbid, precipitation, variable color, gas leakage.
(4) medication first should be selected low dose for use, instil at a slow speed, and to the careful usefulness of Flos Carthami powder allergy sufferers, anemia of pregnant woman's forbidding.Accidental erythra.
Writing out a prescription with this is that the oral formulations that make on the basis has capsule formulation, and Chinese patent discloses its injection dosage form No. 93101867.6, and its characteristics, effect are identical, come out but still there is drops so far.
Owing to reasons such as technologies of preparing, the oral formulations of most drug, exist all 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 lower, thereby influence the performance of drug effect, also directly affect therapeutic effect.Owing to be subjected to the influence of existing injection technology of preparing restriction and Chinese medicinal ingredients complexity, Chinese medicine injection often is easy to generate acute allergic reaction or untoward reaction, it is big also to exist operation easier simultaneously, the patient suffering is big, make and the medical treatment cost height, transportation stores inconvenience, and patient economy burden is heavy, shortcomings such as unsuitable family use.Therefore, be necessary to seek the peroral dosage form of better Flos Carthami medicine to satisfy the needs that clinical treatment and family use.
In addition, conventional peroral dosage form as tablet, capsule etc., because the technology of granulation is arranged, therefore can produce bigger dust pollution in preparation process, can staff's health be worked the mischief to a certain extent, also can cause certain pollution to environment simultaneously.Moreover, the complex manufacturing of conventional oral formulations, production cost is higher, thereby patient's drug cost is also improved thereupon, is unfavorable for improving the ability of seeking medical advice of extensive patients, also is unfavorable for improving the general health level of society.
Summary of the invention
Purpose of the present invention, be to replenish the existing obliterated cerebral vascular disease that is used for the treatment of, coronary heart disease, the deficiency of the oral drug preparation of diseases such as vasculitis provides a kind of bioavailability height, release fast, quick produce effects, toxic and side effects is little, and manufacturing and medical treatment cost are low, low price, the safflower dripping pill that is suitable for family to use.
Safflower dripping pill involved in the present invention determines that through a large amount of experiment sievings based on Chinese traditional patent formulation Flos Carthami injection extraction process, process is adjusted extracting section technology, and cooperates drop pill preparation technology to be prepared from.Be prepared by the following technical solutions, can obtain safflower dripping pill involved in the present invention:
[preparation method]
1. be unit with g or kg, calculate, get the Flos Carthami of some according to weight, through the extracting method of routine make the drug extract thick paste or dry powder standby;
2. substrate---Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), one or more the mixture 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;
3. proportioning---with g or kg is unit, by weight, and drug extract: substrate=1: 1～1: 9.
4. 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;
5. 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) ℃;
6. treating that the temperature of condensing agent in dropping-pill machine head and the condensation column is stable respectively is in above the 2nd step during desired state of temperature, fused solution and/or the emulsion and/or the suspension that will contain drug extract and substrate, under the temperature conditions close, make evenly through fully stirring with the water dropper temperature, under the state of insulation, place in the water dropper jar of drop pill machine, splash in the condensing agent by water dropper;
Condensing agent can be any one in liquid paraffin, methyl-silicone oil, the vegetable oil;
7. 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: a kind of preparation method of Chinese medicine extract]
With g or kg is unit, takes by weighing the Flos Carthami of some according to weight, decocts with water three times, 1 hour for the first time, 50 minutes for the second time, 30 minutes for the third time, collecting decoction filters, and filtrate is concentrated into relative density 1.16～1.26, add ethanol and make and contain alcohol amount and reach 70%, cold preservation was left standstill 48 hours, filter, filtrate recycling ethanol, and to be concentrated into relative density be 1.10～1.14 adds ethanol again and makes and contain the alcohol amount and reach 80%, cold 48 hours, filter, filtrate recycling ethanol and to be concentrated into relative density be 1.16～1.20 adds 10 times of water gagings, cold preservation, left standstill 16～24 hours, and filtered, filtrate is at 0.1Mpa, be condensed into relative density under 60 ℃ the condition and be 1.3～1.35 thick paste, or with thick paste through the low-temperature reduced-pressure drying, pulverize, promptly get dry powder;
Given here is according to a kind of preparation method of extract comparatively commonly used, its processing step adjustment is formed again.Similarly method is a lot, is not limited to this a kind of method during actual enforcement.
Beneficial effect
The Flos Carthami injection that is prepared from according to the prescription that provides among the drug standard WS3-B-3825-98 promulgated by the ministries or commissions of the Central Government of country and extraction process, it is a kind of obliterated cerebral vascular disease that is used for the treatment of, coronary heart disease, the pure Chinese medicine of diseases such as vasculitis, through clinical verification for many years, steady quality, determined curative effect is the common drug that is used for the treatment of above-mentioned disease clinically.This product has been made into dosage forms such as injection, capsule at present.
Owing to reasons such as technologies of preparing, the oral formulations of most drug, especially the oral formulations of Chinese medicine, exist all 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 lower, thereby influence the performance of drug effect, also directly affect therapeutic effect.
In addition, conventional peroral dosage form as tablet, capsule etc., because the technology of granulation is arranged, therefore can produce bigger dust pollution in preparation process, can staff's health be worked the mischief to a certain extent, also can cause certain pollution to environment simultaneously.Moreover, the complex manufacturing of conventional oral formulations, production cost is higher, thereby patient's drug cost is also improved thereupon, is unfavorable for improving the ability of seeking medical advice of extensive patients, also is unfavorable for improving the general health level of society.
Safflower dripping pill involved in the present invention is compared with Flos Carthami injection, and following beneficial effect is arranged:
1. safflower dripping pill involved in the present invention; utilize surfactant to be substrate; make solid dispersion with extractum that contains the Flos Carthami active constituents of medicine or dry powder; making medicine be molecule, colloid or microcrystalline state is scattered in the substrate; the total surface area of medicine increases, and substrate is hydrophilic, and medicine is had wetting action; can make that medicine is rapidly molten to loose into microgranule or solution, thereby make the dissolving of medicine and absorb and accelerate.Thereby improved bioavailability, brought into play efficient, quick-acting effects etc.
Compare with the administering mode of traditional oral formulations, exist essential distinction.Drop pill with the solid dispersion technology preparation can adopt oral and sublingual administration, and effective ingredient is fully contacted with mucomembranous surface, absorbs by mucomembranous epithelial cell, directly enters blood circulation.Owing to directly enter blood circulation without gastrointestinal tract and liver, avoided first pass effect effectively, also avoided gastrointestinal irritation, thereby it is rapid to have an onset, bioavailability height, characteristics such as side effect is little, and medication is convenient.
Chinese patent medicine injection series products is because of producing and basic research seriously lags behind, and the standardization issue of medicine never is resolved.The Chinese crude drug raw material itself is exactly a miscellaneous complex of chemical constituent, also do not have a kind of effective quality control method can reflect the quality and the difference thereof of product comprehensively, comprehensively, truly so far, and can carry out effectively the production overall process quality control, cause the drug quality instability.The untoward reaction of Chinese medicine at present happens occasionally, but can't fundamentally understand fully to be due to which kind of composition, therefore can not in time make and deal with the aftermath of remedial measure targetedly, stay hidden danger for the hospital clinical medication.Injection manufacturing in addition, cost of transportation height use inconvenience, and this had both increased the weight of patient economy burden, have increased the misery of using again.Compare with Flos Carthami injection, the oral administration dripping pill agent has avoided medicine directly into blood, can reduce acute toxic and side effects and anaphylactoid generation effectively, and is safe and convenient to use, and effect is lasting, applied range; Manufacturing and medical treatment cost reduce greatly simultaneously, have effectively alleviated patient's financial burden, and have stored, transport, carry and use all more convenient.
2. safflower dripping pill involved in the present invention contacts promptly with saliva and to dissolve rapidly, and is absorbed by oral mucosa, and is not only rapid-action, and the influence of not taken food, and promptly all can containing take after meal ante cibum.
3. safflower dripping pill involved in the present invention mixes the extract that contains active constituents of medicine mutually with molten matrix, splashes in the not miscible condensed fluid and makes.Therefore, the stability of drug height, not facile hydrolysis, oxidation, and the operation be under liquid state, to carry out, no dust pollution is not subject to the influence of crystal formation, thereby has guaranteed the quality of medicine, has increased stability.
In sum, make safflower dripping pill involved in the present invention have the advantage of triple effect (quick-acting, efficient, long-acting), three little (taking dose is little, toxicity is little, side effect little), five convenience (convenient for production, store convenience, convenient transportation, easy to carry, easy to use), meet the basic demand of modernization of Chinese medicine theory.
The specific embodiment
Now with several groups of specific embodiments, be described further with regard to the preparation method of safflower dripping pill of the present invention.
First group: the test of single-matrix
1. the ratio that provides according to [preparation method] 1 takes by weighing the raw material of Chinese medicine of some, makes earlier according to [appendix: a kind of preparation method of Chinese medicine extract] one joint that to contain Chinese medicine safflower extraction of active ingredients thing dry powder standby again;
2. substrate: Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), pharmaceutically suitable carrier such as polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac;
3. proportioning---with g or kg is unit, by weight, and drug extract: substrate=1: 1～1: 9;
4. be prepared according to the process of [preparation method] 4～7 again, promptly can make the safflower dripping pill of various different sizes.
[result of the test]
Test 1: for observe drug extract and different substrates when 1: 1 the proportioning prepared safflower dripping pill in qualitative difference, according to 1: 1 ratio, with drug 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 drug extract and different substrates, and obtain 15 groups of different experimental results and see Table 1.
Test 2: for observe drug extract and different substrates when 1: 3 the proportioning prepared safflower dripping pill in qualitative difference, according to 1: 3 ratio, with drug 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 the experiment of 15 pharmaceutical compositions that drug extract and different substrates constituted, and obtain 15 groups of different experimental results and see Table 2.
Test 3: for observe drug extract and different substrates when 1: 9 the proportioning prepared safflower dripping pill in qualitative difference, according to 1: 9 ratio, with drug 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 the experiment of 15 pharmaceutical compositions that drug extract and different substrates constituted, and obtain 15 groups of different experimental results and see Table 3.
Second group: the test of mixed-matrix
1. the ratio that provides according to [preparation method] 1 takes by weighing the raw material of Chinese medicine of some, and it is standby to make the extract dry powder that contains the Chinese medicine safflower active constituents of medicine earlier according to [appendix: a kind of preparation method of Chinese medicine extract] joint again;
2. substrate:
2.1 Polyethylene Glycol---English name Macrogol,
2.2 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,
2.3 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 2.4 carboxymethyl starch sodium---English name Carboxymethylstach Sodium, starch generates with the monoxone effect under alkali condition,
2.5 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;
3. (with g or kg is unit to proportioning, by weight)
3.1 the ratio of composite interstitial substance---polyoxyethylene stearate 40 esters: Polyethylene Glycol or poloxamer: Polyethylene Glycol or carboxymethyl starch sodium: Polyethylene Glycol or betacyclodextrin: Polyethylene Glycol=1: 1～1: 10,
3.2 hybrid medicine extract: mixed-matrix weight and=1: 1～1: 9,
4. be prepared according to [preparation method] again, promptly can make the safflower dripping pill of various different sizes.
[result of the test]
Test 4: for observe drug extract and mixed-matrix when 1: 1 the proportioning prepared safflower dripping pill in qualitative difference, 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, according to 1: 1 ratio drug extract is mixed mutually with 4 kinds of different mixed-matrixes again and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that drug extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 4.
Test 5: for observe drug extract and mixed-matrix when 1: 3 the proportioning prepared safflower dripping pill in qualitative difference, 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, according to 1: 3 ratio drug extract is mixed mutually with 4 kinds of different mixed-matrixes again and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that drug extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 5.
Test 6: for observe drug extract and mixed-matrix when 1: 9 the proportioning prepared safflower dripping pill in qualitative difference, 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, according to 1: 9 ratio drug extract is mixed mutually with 4 kinds of different mixed-matrixes again and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that drug extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 6.
Test 7: for observe drug extract and mixed-matrix when 1: 1 the proportioning prepared safflower dripping pill in qualitative difference, 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, according to 1: 1 ratio drug extract is mixed mutually with 4 kinds of different mixed-matrixes again and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that drug extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 7.
Test 8: for observe drug extract and mixed-matrix when 1: 3 the proportioning prepared safflower dripping pill in qualitative difference, 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, according to 1: 3 ratio drug extract is mixed mutually with 4 kinds of different mixed-matrixes again and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that drug extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 8.
Test 9: for observe drug extract and mixed-matrix when 1: 9 the proportioning prepared safflower dripping pill in qualitative difference, 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, according to 1: 9 ratio drug extract is mixed mutually with 4 kinds of different mixed-matrixes again and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that drug extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 9.
Test 10: for observe drug extract and mixed-matrix when 1: 1 the proportioning prepared safflower dripping pill in qualitative difference, 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, according to 1: 1 ratio drug extract is mixed mutually with 4 kinds of different mixed-matrixes again and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that drug extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 10.
Test 11: for observe drug extract and mixed-matrix when 1: 3 the proportioning prepared safflower dripping pill in qualitative difference, 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, according to 1: 3 ratio drug extract is mixed mutually with 4 kinds of different mixed-matrixes again and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that drug extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 11.
Test 12: for observe drug extract and mixed-matrix when 1: 9 the proportioning prepared safflower dripping pill in qualitative difference, 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, according to 1: 9 ratio drug extract is mixed mutually with 4 kinds of different mixed-matrixes again and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that drug 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 | 62 | ＜30 | ＞10 | + |
| Polyethylene Glycol 4000 | 50.0 | 77 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 6000 | 50.0 | 81 | ＜30 | ＞10 | +++ |
| Polyethylene Glycol 8000 | 50.0 | 83 | ＜30 | ＞10 | +++ |
| Polyethylene Glycol 10000 | 50.0 | 87 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 20000 | 50.0 | 86 | ＜30 | ＜10 | +++ |
| Polyoxyethylene stearate 40 esters | 50.0 | 75 | ＜30 | ＞10 | ++ |
| Betacyclodextrin | 50.0 | 70 | ＜30 | ＞10 | ++ |
| Poloxamer | 50.0 | 71 | ＜30 | ＞10 | ++ |
| Carboxymethyl starch sodium | 50.0 | 71 | ＜30 | ＞10 | ++ |
| Sodium lauryl sulphate | 50.0 | 69 | ＜30 | ＞10 | ++ |
| Stearic acid | 50.0 | 54 | ＜30 | ＞10 | ++ |
| Sodium stearate | 50.0 | 54 | ＜30 | ＞10 | +++ |
| Glycerin gelatine | 50.0 | 55 | ＜30 | ＞10 | +++ |
| Lac | 50.0 | 51 | ＞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 | 78 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 4000 | 25.0 | 85 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 6000 | 25.0 | 91 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 8000 | 25.0 | 90 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 10000 | 25.0 | 93 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 20000 | 25.0 | 92 | ＜30 | ＜10 | +++ |
| Polyoxyethylene stearate 40 esters | 25.0 | 86 | ＜30 | ＜10 | ++ |
| Betacyclodextrin | 25.0 | 82 | ＜30 | ＜10 | ++ |
| Poloxamer | 25.0 | 85 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium | 25.0 | 81 | ＜30 | ＞10 | ++ |
| Sodium lauryl sulphate | 25.0 | 76 | ＜30 | ＞10 | ++ |
| Stearic acid | 25.0 | 72 | ＞30 | ＞10 | ++ |
| Sodium stearate | 25.0 | 73 | ＞30 | ＞10 | +++ |
| Glycerin gelatine | 25.0 | 68 | ＞30 | ＞10 | +++ |
| Lac | 25.0 | 69 | ＞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 | 83 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 4000 | 10.0 | 88 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 6000 | 10.0 | 92 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 8000 | 10.0 | 93 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 10000 | 10.0 | 93 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 20000 | 10.0 | 94 | ＜30 | ＜10 | +++ |
| Polyoxyethylene stearate 40 esters | 10.0 | 89 | ＜30 | ＜10 | ++ |
| Betacyclodextrin | 10.0 | 87 | ＜30 | ＜10 | ++ |
| Poloxamer | 10.0 | 92 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium | 10.0 | 82 | ＜30 | ＞10 | +++ |
| Sodium lauryl sulphate | 10.0 | 81 | ＜30 | ＞10 | +++ |
| Stearic acid | 10.0 | 79 | ＞30 | ＞10 | +++ |
| Sodium stearate | 10.0 | 80 | ＞30 | ＞10 | +++ |
| Glycerin gelatine | 10.0 | 74 | ＞30 | ＞10 | +++ |
| Lac | 10.0 | 77 | ＞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 | 83 | ＜30 | ＞10 | ++ |
| Poloxamer: Polyethylene Glycol=1: 1 | 50 | 82 | ＜30 | ＞10 | ++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | 50 | 77 | ＜30 | ＞10 | ++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | 50 | 73 | ＜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 | 87 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 1 | 25 | 88 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | 25 | 83 | ＜30 | ＞10 | ++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | 25 | 81 | ＜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 | 84 | ＜30 | ＞10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | 10 | 82 | ＜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 | 93 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 5 | 50 | 87 | ＜30 | ＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | 50 | 83 | ＜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 | 92 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 5 | 25 | 91 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 5 | 25 | 89 | ＜30 | ＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | 25 | 87 | ＜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 | 94 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 5 | 10 | 93 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 5 | 10 | 91 | ＜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 | 85 | ＜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 | 91 | ＜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 | 86 | ＜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 | 92 | ＜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, though the rounding rate, the ball method of double differences is different and index such as hardness has raising, and is 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.
Claims (2)
1. a safflower dripping pill that is used for the treatment of cardiovascular and cerebrovascular disease is a raw material with the Chinese medicine safflower, is prepared from a certain proportion of pharmaceutically suitable carrier, it is characterized in that described preparation process is as follows:
(1) it is an amount of to get Flos Carthami, decocts with water 1 hour for the first time three times, 50 minutes for the second time, 30 minutes for the third time, collecting decoction, filter, filtrate is concentrated into relative density 1.16～1.26, adds ethanol and makes and contain the alcohol amount and reach 70%, cold preservation was left standstill 48 hours, filtered, filtrate recycling ethanol, and to be concentrated into relative density be 1.10～1.14, adds ethanol again and make and contain the alcohol amount and reach 80%, cold preservation, left standstill 48 hours, filter, filtrate recycling ethanol and to be concentrated into relative density be 1.16～1.20 adds 10 times of water gagings, cold preservation, left standstill 16～24 hours, and filtered, filtrate is at 0.1Mpa, be condensed into relative density under 60 ℃ the condition and be 1.3～1.35 thick paste, or again through low temperature, drying under reduced pressure is pulverized, and promptly gets Flos Carthami extract dry powder.
(2) described substrate is the mixture of Polyethylene Glycol and polyoxyethylene stearate 40 esters or poloxamer or carboxymethyl starch sodium; By weight, the ratio of polyoxyethylene stearate 40 esters or poloxamer or carboxymethyl starch sodium and Polyethylene Glycol is 1: 1～1: 10; The ratio of described Flos Carthami extract and substrate is 1: 3;
(3) according to aforementioned proportion, accurately take by weighing Flos Carthami extract and substrate, be placed in the heating container heating while stirring, standby until the fused solution that obtains containing drug extract and substrate and/or emulsion and/or suspension;
(4) temperature control system of adjustment drop pill machine makes the water dropper temperature heating of drop pill machine and remains on 50 ℃～90, and the temperature cooling of condensing agent also remains on-5 ℃～40 ℃;
When (5) temperature for the treatment of dropping-pill machine head and condensing agent reaches the said temperature state respectively, will contain fused solution and/or the emulsion and/or the suspension of Flos Carthami extract and substrate, place in the water dropper jar of drop pill machine, and splash into to shrink in the condensing agent and be shaped promptly.
2. safflower dripping pill as claimed in claim 1 is characterized in that: described condensing agent be methyl-silicone oil or/and liquid paraffin or/and vegetable oil.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100963265A CN1307975C (en) | 2004-11-30 | 2004-11-30 | Safflower drop pills and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100963265A CN1307975C (en) | 2004-11-30 | 2004-11-30 | Safflower drop pills and preparation method thereof |
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| Publication Number | Publication Date |
|---|---|
| CN1634482A CN1634482A (en) | 2005-07-06 |
| CN1307975C true CN1307975C (en) | 2007-04-04 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNB2004100963265A Expired - Fee Related CN1307975C (en) | 2004-11-30 | 2004-11-30 | Safflower drop pills and preparation method thereof |
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Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105687282A (en) * | 2015-12-17 | 2016-06-22 | 北京大学 | Parkinson's disease resistance safflower carthamus effective part dropping pill and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1114219A (en) * | 1995-03-08 | 1996-01-03 | 鲁洪艺 | Process for preparing Chinese drugs for curing coronary heart disease, angina pectoris and myocardiac infarction |
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2004
- 2004-11-30 CN CNB2004100963265A patent/CN1307975C/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1114219A (en) * | 1995-03-08 | 1996-01-03 | 鲁洪艺 | Process for preparing Chinese drugs for curing coronary heart disease, angina pectoris and myocardiac infarction |
Non-Patent Citations (1)
| Title |
|---|
| 红花提取物抗血小板聚集及抗血栓作用的观察 刘志峰 李萍 李桂生 傅风华 刘珂，中药药理与临床，第16卷第6期 2000 * |
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| CN1634482A (en) | 2005-07-06 |
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