CN1634508A - Saussurea involucrata drop pill and its preparation method - Google Patents
Saussurea involucrata drop pill and its preparation method Download PDFInfo
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- CN1634508A CN1634508A CN 200410097158 CN200410097158A CN1634508A CN 1634508 A CN1634508 A CN 1634508A CN 200410097158 CN200410097158 CN 200410097158 CN 200410097158 A CN200410097158 A CN 200410097158A CN 1634508 A CN1634508 A CN 1634508A
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Abstract
The invention relates to a medicinal oral preparation, i.e., a saussurea involucrata drop pill for treating rheumatic arthritis, chronic infectious arthritis and dysmenorrheal, which has the advantages of high biological availability, quick-speed medicine release, quick-speed effect, less toxic and side effects, higher medicinal content, smaller amount of administration, accurate administration dosage, easy administration, low price, and facilitated carrying. The medicine is prepared through the conventional drop pill preparing process.
Description
Technical field
The present invention relates to a kind of warming the kidney to activate YANG that has, expelling wind and dampness, the promoting blood circulation to restore menstrual flow effect, be used for the treatment of insufficiency of kidney-YANG, rheumatic arthritis due to the cold and damp stagnation, the pharmaceutical composition of disease such as rheumatoid arthritis and dysmenorrhea particularly based on saussurea involucrata oral liquid, is changed a social system a kind of drug composition oral dropping pill formulation that forms through dosage form.
Background technology
The saussurea involucrata oral liquid that is prepared from according to the prescription that provides among the national drug standards WS-10155 (ZD-0155)-2002 and extraction process, it is a kind of warming the kidney to activate YANG that has, expelling wind and dampness, the promoting blood circulation to restore menstrual flow effect is used for the treatment of insufficiency of kidney-YANG, rheumatic arthritis due to the cold and damp stagnation, the Chinese medicine preparation of disease such as rheumatoid arthritis and dysmenorrhea, through clinical verification, steady quality, determined curative effect is the oral drug preparation commonly used that clinical and family is used for the treatment of above disease.
Below be prescription and the extraction process that provides among the drug standard WS-10155 (ZD-0155)-2002:
Prescription: Herba Saussureae Involueratae 150g, simple syrup 294ml, citric acid 0.65g;
Method for making: get Herba Saussureae Involueratae, use 65% ethanol, heating and refluxing extraction secondary, 1.5 hours for the first time, 1 hour for the second time, merge extractive liquid, filtered filtrate recycling ethanol, be concentrated into about 600ml, add ethanol and make and contain the alcohol amount and reach 65%, 4 ℃ of cold preservation 24 hours, get supernatant, filter, filtrate recycling ethanol adds simple syrup, citric acid to there not being the alcohol flavor, stir evenly, add water to ormal weight, stir evenly, fill, sterilization, promptly;
Be explained as follows for said preparation in the appended saussurea involucrata oral liquid description:
Nomenclature of drug: saussurea involucrata oral liquid;
Main component: Herba Saussureae Involueratae;
Character: this product is a rufous liquid; Sweet, little hardship of distinguishing the flavor of;
Function cures mainly: warming the kidney to activate YANG, expelling wind and dampness, promoting blood circulation to restore menstrual flow.Be used for insufficiency of kidney-YANG, the rheumatic arthritis due to the cold and damp stagnation, rheumatoid arthritis and dysmenorrhea etc.;
Usage and dosage: oral, a 10-20ml, 1～2 time on the one, sooner or later (medicine) being taken before meal with or follow the doctor's advice;
Writing out a prescription with this is that other oral formulations that make on the basis have capsule, tablet; Also have the injection dosage form in addition, its characteristics, effect are identical.
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.Oral liquid exists simultaneously that medicament contg is low, and taking dose is big, and taking dose is inaccurate, takes the high characteristics of inconvenience and production cost, also is not easy to go out to carry.Because of being 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 Herba Saussureae Involueratae 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 is to replenish the existing insufficiency of kidney-YANG that is used for the treatment of, the rheumatic arthritis due to the cold and damp stagnation, the deficiency of the oral drug preparation of disease such as rheumatoid arthritis and dysmenorrhea provides a kind of bioavailability height, release fast, quick produce effects, toxic and side effects is littler, and the medicament contg height, and taking dose is little, taking dose is accurate, taking convenience, cheap, and be convenient to the drug composition oral preparation Saussurea involucrata drop pill of going out to carry.
Saussurea involucrata drop pill involved in the present invention determines that through a large amount of experiment sievings based on the extraction process of Chinese traditional patent formulation saussurea involucrata oral liquid, 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 Saussurea involucrata drop pill involved in the present invention:
[preparation method]
1. be unit with g or kg,, get 1 part of Herba Saussureae Involueratae according to the weight portion meter, through conventional extraction process 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 3. ratios that provide, accurately take by weighing drug extract and substrate, gradation is progressively inserted in the heating container, and heating while stirring is 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-5 ℃～40 ℃;
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, insulation, place in the water dropper jar of drop pill machine, splash in the condensing agent by water dropper
Condensing agent can be in liquid paraffin, methyl-silicone oil, the vegetable oil arbitrarily～kind;
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.
[a kind of preparation method of drug extract]
With g or kg is unit, according to the weight portion meter, gets 1 part of Herba Saussureae Involueratae, uses 65% ethanol, the heating and refluxing extraction secondary, 1.5 hours for the first time, 1 hour for the second time, merge extractive liquid, filters, and filtrate recycling ethanol concentrates, add ethanol and make and contain the alcohol amount and reach 65%, 4 ℃ of cold preservation 24 hours, get supernatant, filter, filtrate recycling ethanol is not to there being the alcohol flavor, and the cryoconcentration that reduces pressure then is 1.3～1.4 thick paste to relative density, or with thick paste at 0.1Mpa, drying and crushing under 60 ℃ the condition promptly gets 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 saussurea involucrata oral liquid that is prepared from according to the prescription that provides among the national drug standards WS-10155 (ZD-0155)-2002 and extraction process, it is a kind of warming the kidney to activate YANG that has, expelling wind and dampness, the promoting blood circulation to restore menstrual flow effect is used for the treatment of insufficiency of kidney-YANG, rheumatic arthritis due to the cold and damp stagnation, the Chinese medicine preparation of disease such as rheumatoid arthritis and dysmenorrhea, through clinical verification, steady quality, determined curative effect is the oral drug preparation commonly used that clinical and family is used for the treatment of above disease.This product also have at present tablet, capsule, injection and etc. dosage form.
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.Oral liquid exists simultaneously that medicament contg is low, and taking dose is big, and taking dose is inaccurate, takes the high characteristics of inconvenience and production cost, also is not easy to go out to carry.Because of being 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.
Saussurea involucrata drop pill involved in the present invention is compared with saussurea involucrata oral liquid, tablet, capsule and injection has following beneficial effect:
1. Saussurea involucrata drop pill involved in the present invention; utilize surfactant to be substrate; make solid dispersion with extractum that contains the Herba Saussureae Involueratae active constituents of medicine or dry powder, make medicine be molecule, colloid or microcrystalline state and be scattered in the substrate, the total surface area of medicine increases; and substrate is hydrophilic; 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 other peroral dosage form, exist essential distinction.Utilize the drop pill of solid dispersion technology preparation, can adopt oral and sublingual administration, effective ingredient is fully contacted with mucomembranous surface, absorb, directly enter blood circulation by mucomembranous epithelial cell.Because active constituents of medicine directly enters blood circulation without gastrointestinal tract and liver, has avoided first pass effect effectively, has also avoided gastrointestinal irritation, thereby it is rapid to make Saussurea involucrata drop pill involved in the present invention have an onset, the bioavailability height, side effect is little, characteristics such as medication convenience.
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 there is not 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 the quality control of production overall process effectively, 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. Saussurea involucrata drop 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. Saussurea involucrata drop 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 Saussurea involucrata drop 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).
The specific embodiment
Now with several groups of specific embodiments, be described further with regard to the preparation method of Saussurea involucrata drop pill of the present invention.
First group: the test of single-matrix
1. make earlier according to [a kind of preparation method of drug extract] one joint that to contain Herba Saussureae Involueratae extraction of active ingredients thing dry powder standby;
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 [preparation method] again, promptly can make the Saussurea involucrata drop pill of various different sizes.
[result of the test]
Test 1: for observe drug extract and different substrates when 1: 1 the proportioning prepared Saussurea involucrata drop 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 Saussurea involucrata drop 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 15 pharmaceutical compositions experiments that contain drug extract and different substrates, 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 Saussurea involucrata drop 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 15 pharmaceutical compositions experiments that contain drug extract and different substrates, and obtain 15 groups of different experimental results and see Table 3.
Second group: the test of mixed-matrix
1. make earlier according to [a kind of preparation method of drug extract] one joint that to contain Herba Saussureae Involueratae extraction of active ingredients thing dry powder standby;
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 Saussurea involucrata drop pill of various different sizes.
[result of the test]
Test 4: for observe drug extract and mixed-matrix when 1: 1 the proportioning prepared Saussurea involucrata drop 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 Saussurea involucrata drop 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 Saussurea involucrata drop 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 Saussurea involucrata drop 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 Saussurea involucrata drop 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 Saussurea involucrata drop 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 Saussurea involucrata drop 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 Saussurea involucrata drop 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 Saussurea involucrata drop 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 | ??64 | ??＜30 | ??＞10 | + |
| Polyethylene Glycol 4000 | ??50.0 | ??78 | ??＜30 | ??＞10 | ++ |
| Polyethylene Glycol 6000 | ??50.0 | ??77 | ??＜30 | ??＞10 | ++ |
| Polyethylene Glycol 8000 | ??50.0 | ??78 | ??＜30 | ??＞10 | ++ |
| Polyethylene Glycol 10000 | ??50.0 | ??80 | ??＜30 | ??＞10 | ++ |
| Polyethylene Glycol 20000 | ??50.0 | ??81 | ??＜30 | ??＞10 | ++ |
| Polyoxyethylene stearate 40 esters | ??50.0 | ??76 | ??＜30 | ??＞10 | ++ |
| Betacyclodextrin | ??50.0 | ??68 | ??＜30 | ??＞10 | + |
| Poloxamer | ??50.0 | ??73 | ??＜30 | ??＞10 | ++ |
| Carboxymethyl starch sodium | ??50.0 | ??70 | ??＜30 | ??＞10 | + |
| Sodium lauryl sulphate | ??50.0 | ??66 | ??＞30 | ??＞10 | ++ |
| Stearic acid | ??50.0 | ??53 | ??＞30 | ??＞10 | +++ |
| Sodium stearate | ??50.0 | ??55 | ??＞30 | ??＞10 | +++ |
| Glycerin gelatine | ??50.0 | ??54 | ??＞30 | ??＞10 | +++ |
| Lac | ??50.0 | ??53 | ??＞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 | ??85 | ??＜30 | ??＜10 | ++ |
| Polyethylene Glycol 6000 | ??25.0 | ??90 | ??＜30 | ??＜10 | +++ |
| Polyethylene Glycol 8000 | ??25.0 | ??92 | ??＜30 | ??＜10 | +++ |
| Polyethylene Glycol 10000 | ??25.0 | ??90 | ??＜30 | ??＜10 | +++ |
| Polyethylene Glycol 20000 | ??25.0 | ??91 | ??＜30 | ??＜10 | ++ |
| Polyoxyethylene stearate 40 esters | ??25.0 | ??93 | ??＜30 | ??＜10 | ++ |
| Betacyclodextrin | ??25.0 | ??81 | ??＜30 | ??＞10 | ++ |
| Poloxamer | ??25.0 | ??88 | ??＜30 | ??＜10 | +++ |
| Carboxymethyl starch sodium | ??25.0 | ??82 | ??＜30 | ??＞10 | ++ |
| Sodium lauryl sulphate | ??25.0 | ??76 | ??＜30 | ??＞10 | ++ |
| Stearic acid | ??25.0 | ??70 | ??＞30 | ??＞10 | +++ |
| Sodium stearate | ??25.0 | ??71 | ??＞30 | ??＞10 | +++ |
| Glycerin gelatine | ??25.0 | ??69 | ??＞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 | ??84 | ??＜30 | ??＞10 | ++ |
| Polyethylene Glycol 4000 | ??10.0 | ??89 | ??＜30 | ??＜10 | +++ |
| Polyethylene Glycol 6000 | ??10.0 | ??93 | ??＜30 | ??＜10 | +++ |
| Polyethylene Glycol 8000 | ??10.0 | ??92 | ??＜30 | ??＜10 | +++ |
| Polyethylene Glycol 10000 | ??10.0 | ??93 | ??＜30 | ??＜10 | +++ |
| Polyethylene Glycol 20000 | ??10.0 | ??93 | ??＜30 | ??＜10 | +++ |
| Polyoxyethylene stearate 40 esters | ??10.0 | ??89 | ??＜30 | ??＜10 | ++ |
| Betacyclodextrin | ??10.0 | ??87 | ??＜30 | ??＜10 | ++ |
| Poloxamer | ??10.0 | ??93 | ??＜30 | ??＜10 | +++ |
| Carboxymethyl starch sodium | ??10.0 | ??82 | ??＜30 | ??＞10 | +++ |
| Sodium lauryl sulphate | ??10.0 | ??82 | ??＜30 | ??＞10 | +++ |
| Stearic acid | ??10.0 | ??79 | ??＞30 | ??＞10 | +++ |
| Sodium stearate | ??10.0 | ??80 | ??＞30 | ??＞10 | +++ |
| Glycerin gelatine | ??10.0 | ??73 | ??＞30 | ??＞10 | +++ |
| Lac | ??10.0 | ??75 | ??＞30 | ??＞10 | +++ |
The group practices of table 4 drug extract and mixed-matrix
(drug extract: mixed-matrix=1: 1)
| The substrate title | Composition (%) is arranged | 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 | ??78 | ??＜30 | ??＞10 | ++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | ??50 | ??76 | ??＜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 | ??89 | ??＜30 | ??＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 1 | ??25 | ??90 | ??＜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 | ??87 | ??＜30 | ??＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 1 | ??10 | ??85 | ??＜30 | ??＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | ??10 | ??82 | ??＜30 | ??＞10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | ??10 | ??84 | ??＜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 | ??86 | ??＜30 | ??＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | 50 | ??84 | ??＜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 | ??90 | ??＜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 | ??91 | ??＜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 | ??88 | ??＜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 | ??93 | ??＜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 | ??92 | ??＜30 | ??＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 10 | ??10 | ??93 | ??＜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 (7)
1. one kind is used for the treatment of insufficiency of kidney-YANG, rheumatic arthritis due to the cold and damp stagnation, the pharmaceutical composition Saussurea involucrata drop pill of disease such as rheumatoid arthritis and dysmenorrhea, with the Herba Saussureae Involueratae is raw material of Chinese medicine, after extraction obtains containing the drug extract of active constituents of medicine, be prepared from a certain proportion of pharmaceutically suitable carrier again, wherein:
1.1. with g or kg is unit, according to the weight portion meter, gets 1 part of Herba Saussureae Involueratae, makes drug extract thick paste or dry powder through extraction process;
1.2. 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;
1.3. proportioning---with g or kg is unit, by weight, and drug extract: substrate=1: 1～1: 9.
2. Saussurea involucrata drop pill as claimed in claim 1 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.
3. any Fel Ursi Bulbus Fritillariae Cirrhosae drop pill as claimed in claim 1 or 2, it is characterized in that: the mixed proportion of described drug extract and substrate is 1: 1～1: 5.
4. Saussurea involucrata drop pill as claimed in claim 1, it is characterized in that described drug extract thick paste or dry powder obtain by the following method: with g or kg is unit, according to the weight portion meter, gets 1 part of Herba Saussureae Involueratae, use 65% ethanol, the heating and refluxing extraction secondary, 1.5 hours for the first time, 1 hour for the second time, merge extractive liquid,, filter, filtrate recycling ethanol concentrates, and adds ethanol and makes and contain the alcohol amount and reach 65%, 4 ℃ of cold preservation 24 hours, get supernatant, filter, filtrate recycling ethanol is to there not being the alcohol flavor, the cryoconcentration that reduces pressure then is 1.3～1.4 thick paste to relative density, or with thick paste at 0.1Mpa, drying and crushing under 60 ℃ the condition promptly gets dry powder.
5. the preparation method of a Saussurea involucrata drop pill is characterized in that being made of following process:
5.1. with g or kg is unit, according to the weight portion meter, gets 1 part of Herba Saussureae Involueratae, through extraction process make the drug extract thick paste or dry powder standby;
5.2. 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;
5.3. proportioning---with g or kg is unit, by weight, and drug extract: substrate=1: 1～1: 9;
5.4., 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;
5.5. adopt homemade or general drop pill machine, and adjust the temperature control system of 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-5 ℃～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, to contain in the fused solution and/or emulsion and/or suspension of drug extract and substrate, under the temperature conditions close, make evenly through fully stirring with the water dropper temperature, insulation, place in the water dropper jar of drop pill machine, splash in the condensing agent by water dropper and shrink shaping promptly.
6. as the preparation method of Saussurea involucrata drop pill as described in the claim 5, it is characterized in that method 5.1 described drug extract thick pastes or dry powder obtain by the following method: with g or kg is unit, according to the weight portion meter, gets 1 part of Herba Saussureae Involueratae, use 65% ethanol, the heating and refluxing extraction secondary, 1.5 hours for the first time, 1 hour for the second time, merge extractive liquid,, filter, filtrate recycling ethanol concentrates, and adds ethanol and makes and contain the alcohol amount and reach 65%, 4 ℃ of cold preservation 24 hours, get supernatant, filter, filtrate recycling ethanol is to there not being the alcohol flavor, the cryoconcentration that reduces pressure then is 1.3～1.4 thick paste to relative density, or with thick paste at 0.1Mpa, drying and crushing under 60 ℃ the condition promptly gets dry powder.
7. as the preparation method of Saussurea involucrata drop pill as described in the claim 5, it is characterized in that: method 5.6 described condensing agents are methyl-silicone oils or/and liquid paraffin or/and vegetable oil.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101209274B (en) * | 2007-12-25 | 2011-05-11 | 新疆维吾尔自治区药物研究所 | Saussurea involucrata extract and and producing method thereof |
| CN102335216A (en) * | 2010-07-14 | 2012-02-01 | 株式会社安露莎 | Melanogenesis inhibitor |
| CN104147071A (en) * | 2014-04-03 | 2014-11-19 | 北京欧凯米特科技有限公司 | Method for extracting effective components from saussurea involucrata |
| CN109350633A (en) * | 2018-09-29 | 2019-02-19 | 大连普瑞康生物技术有限公司 | A kind of Saussurea involucrata culture dripping pill and preparation method thereof |
-
2004
- 2004-12-13 CN CNB2004100971581A patent/CN100348169C/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101209274B (en) * | 2007-12-25 | 2011-05-11 | 新疆维吾尔自治区药物研究所 | Saussurea involucrata extract and and producing method thereof |
| CN102335216A (en) * | 2010-07-14 | 2012-02-01 | 株式会社安露莎 | Melanogenesis inhibitor |
| CN104147071A (en) * | 2014-04-03 | 2014-11-19 | 北京欧凯米特科技有限公司 | Method for extracting effective components from saussurea involucrata |
| CN104147071B (en) * | 2014-04-03 | 2018-03-02 | 北京欧凯米特科技有限公司 | A kind of method of effective component extracting in saussurea involucrata |
| CN109350633A (en) * | 2018-09-29 | 2019-02-19 | 大连普瑞康生物技术有限公司 | A kind of Saussurea involucrata culture dripping pill and preparation method thereof |
| CN109350633B (en) * | 2018-09-29 | 2021-05-14 | 大连普瑞康生物技术有限公司 | Drop pills of saussurea involucrata culture and preparation method |
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| CN100348169C (en) | 2007-11-14 |
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