CN1301107C - Xiyanping drop pills of possessing function of clearing away heat and toxic materia and preparation method - Google Patents
Xiyanping drop pills of possessing function of clearing away heat and toxic materia and preparation method Download PDFInfo
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- CN1301107C CN1301107C CNB2004101040430A CN200410104043A CN1301107C CN 1301107 C CN1301107 C CN 1301107C CN B2004101040430 A CNB2004101040430 A CN B2004101040430A CN 200410104043 A CN200410104043 A CN 200410104043A CN 1301107 C CN1301107 C CN 1301107C
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- andrographolide
- polyethylene glycol
- sulfonated bodies
- drop pill
- xiyanping
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- 238000000034 method Methods 0.000 claims abstract description 23
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- 239000002202 Polyethylene glycol Substances 0.000 claims description 93
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- ASLUCFFROXVMFL-UHFFFAOYSA-N andrographolide Natural products CC1(CO)C(O)CCC2(C)C(CC=C3/C(O)OCC3=O)C(=C)CCC12 ASLUCFFROXVMFL-UHFFFAOYSA-N 0.000 claims description 78
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- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 8
- 239000004141 Sodium laurylsulphate Substances 0.000 description 8
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- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 8
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 8
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 8
- 239000008117 stearic acid Substances 0.000 description 8
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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
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 201000004813 Bronchopneumonia Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 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
- 206010070840 Gastrointestinal tract irritation Diseases 0.000 description 1
- 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 1
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- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
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- 239000008354 sodium chloride injection Substances 0.000 description 1
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Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Medicinal Preparation (AREA)
Abstract
The present invention relates to a medicine composition which has the functions of clearing heat and toxin, relieving cough and alleviating dysentery and is used for the treatment of bronchitic, tonsillitis, bacillary dysentery and other diseases. The present invention has the purpose of complementing the deficiency of the existing oral medicine preparations used for the treatment of bronchitic, tonsillitis, bacillary dysentery and other diseases, and provides xiyanping dripping pills having the advantages of high bioavailability, quick medicine release, rapid effect, little toxic and side effect, high medicine content, accurate administration measurement, convenient administration, low price and low production cost. The Xiyanping dripping pills of the present invention are prepared according to the extraction technique of Xiyanping injecta (Chinese medicine with set prescription).
Description
Technical field
The present invention relates to a kind of heat-clearing and toxic substances removing that has, the cough-relieving dysentery relieving, be used for bronchitis, tonsillitis, the pharmaceutical composition of diseases such as bacillary dysentery treatment, be particularly related to based on Chinese traditional patent formulation Xiyanping injection, through a kind of drug composition oral dropping pill formulation that dosage form is changed a social system and the change route of administration forms.
Background technology
According to the Xiyanping injection that the prescription that provides among the national drug standards WS-10862 (ZD-0863)-2002 and extraction process are prepared from, be a kind of heat-clearing and toxic substances removing that has; The injection class preparation of diseases such as the upper respiratory tract infection that is used for dominance of heat in the interior and causes, bronchopneumonia, viral pneumonia, purulent disease, gynecological inflammation and postoperative fever treatment, through clinical verification for many years, steady quality, determined curative effect is the common drug preparation that clinical and family is used for the treatment of above disease.
Below be the prescription and the extraction process of the Xiyanping injection that provides among the national drug standards WS-10862 (ZD-0863)-2002:
Prescription: andrographolide sulfonated bodies 25g;
Method for making: get the andrographolide sulfonated bodies, dissolve in right amount with water for injection, add 0.1% active carbon and stirred 10 minutes, filter, add the injection water to ormal weight, filter, regulate pH value to 4.5～6.5 with 10% sodium hydroxide solution, embedding is sterilized, promptly.Be explained as follows for this injection in the appended Xiyanping injection description:
Nomenclature of drug: Xiyanping injection;
Main component: andrographolide sulfonated bodies;
Character: this product is faint yellow to orange-yellow clear liquid;
Function cures mainly: heat-clearing and toxic substances removing.The cough-relieving dysentery relieving.Be used for bronchitis, tonsillitis, bacillary dysentery etc.;
Usage and dosage: intramuscular injection.50～the 100mg that is grown up one time, 2～3 times on the one; Children's is cut down according to the circumstance or is followed the doctor's advice.Intravenous drip: 250～500mg on the one adds in 5$ glucose injection or the sodium chloride injection and instils; Children's is cut down according to the circumstance or is followed the doctor's advice.
Owing to reasons such as technologies of preparing, the research of the compatibility of Chinese medicine injection can not show a candle to Western medicine, and causes allergy easily.Existing Xiyanping injection does not still have similar other dosage form listings at present.This kind Chinese medicine is an effective component extracting from Chinese crude drug, the intravital concentrated solution of Gong the injection of making.Because the extensive use of modern biotechnology in the natural drug exploitation, the domestic herbal species that is used to inject is more and more, and application is more and more wider clinically, and adverse reaction rate also increases.According to data: the dosage form of Chinese patent medicine adverse reaction rate is that injection accounts for 31% successively, tablet accounts for 24%, pill accounts for 10%.Chinese medicine untoward reaction consequence is serious, and Chinese medicine and preparation thereof cause anaphylactic shock and rank first place, and the trend that increases is arranged year by year, this with use clinically more relevant.Chinese medicine composition more complicated is injected human body with this mixture from blood vessel, forces human body to go metabolism, and itself has just had potential danger, if again with the other medicines compatibility, contingent reaction often is difficult to prediction.The compatibility difficulty of Chinese medicine is bigger, and incompatibility is studied the compatibility of Chinese medicine without ready patterns to follow, and it is perfect also to can not show a candle to Western medicine.Chinese medicine injection causes allergy easily, and reason is to contain albumen, polysaccharide, polypeptide etc. in its composition; The purity of extracting is not enough; Plurality of Chinese is extracted, and each composition interacts; Contain cosolvent, solubilizing agent etc.
In addition, 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 the peroral dosage form of therapeutic effect routine, as tablet, capsule etc.In addition, in preparation process,, therefore can produce bigger dust pollution, can staff's health be worked the mischief to a certain extent, also can cause certain pollution simultaneously to environment because the technology of granulation is arranged.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 existing be used for the treatment of bronchitis, tonsillitis, the deficiency of the oral drug preparation of symptoms such as bacillary dysentery, provide a kind of bioavailability height, release fast, produce effects fast, toxic and side effects is little, the medicament contg height, taking dose is accurate, taking convenience, cheap, and the lower Xiyanping drop pill of production cost.
Xiyanping drop pill involved in the present invention serves as with reference to being prepared from the extraction process of Chinese traditional patent formulation Xiyanping injection.Be prepared by the following technical solutions, can obtain Xiyanping drop pill involved in the present invention:
[preparation method]
1. andrographolide sulfonated bodies;
2. substrate---one or more the mixture in pharmaceutically suitable carrier such as Polyethylene Glycol (1000～20000), 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 medicine: substrate=1: 1～1: 9.
4. according to the given ratio of prescription, accurately take by weighing medicine andrographolide sulfonated bodies and substrate, be placed in the heating container heating while stirring, standby until the fused solution that obtains containing medicine andrographolide sulfonated bodies 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, and at the temperature conditions close with the water dropper temperature, insulation places in the water dropper jar of drop pill machine, splashes in the condensing agent by water dropper;
Condensing agent can be any one of liquid paraffin, methyl-silicone oil, 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.
Beneficial effect
According to the Xiyanping injection that the prescription that provides among the national drug standards WS-10862 (ZD-0863)-2002 and extraction process are prepared from, be a kind of heat-clearing and toxic substances removing that has; The cough-relieving dysentery relieving.Be used for bronchitis, tonsillitis, the tablet class preparation of symptoms such as bacillary dysentery, through clinical verification for many years, steady quality, determined curative effect is the common drug preparation that clinical and family is used for the treatment of above disease.
Chinese medicine is an effective component extracting from Chinese crude drug, the intravital concentrated solution of Gong the injection of making.Because the extensive use of modern biotechnology in the natural drug exploitation, the domestic herbal species that is used to inject is more and more, and application is more and more wider clinically, and adverse reaction rate also increases.According to data: the dosage form of Chinese patent medicine adverse reaction rate is that injection accounts for 31% successively, tablet accounts for 24%, pill accounts for 10%.Chinese medicine untoward reaction consequence is serious, and Chinese medicine and preparation thereof cause anaphylactic shock and rank first place, and the trend that increases is arranged year by year, this with use clinically more relevant.Chinese medicine composition more complicated is injected human body with this mixture from blood vessel, forces human body to go metabolism, and itself has just had potential danger, if again with the other medicines compatibility, contingent reaction often is difficult to prediction.The compatibility difficulty of Chinese medicine is bigger, and incompatibility is studied the compatibility of Chinese medicine without ready patterns to follow, and it is perfect also to can not show a candle to Western medicine.Chinese medicine injection causes allergy easily, and reason is to contain albumen, polysaccharide, polypeptide etc. in its composition; The purity of extracting is not enough; Plurality of Chinese is extracted, and each composition interacts; Contain cosolvent, solubilizing agent etc.
In addition 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.
Xiyanping drop pill involved in the present invention is compared with the Xiyanping injection, has following beneficial effect:
1. Xiyanping drop pill involved in the present invention; utilize surfactant etc. to be substrate; make solid dispersion with the andrographolide sulfonated bodies that contains active constituents of medicine; making medicine be molecule, colloid or microcrystalline state is scattered in the substrate; the total surface area of medicine increases; and substrate is that medicine has wetting action, can make that medicine is rapidly molten to loose into microgranule or solution, thereby makes the dissolving of medicine and absorb and accelerate.Thereby improved bioavailability, brought into play efficient, quick-acting effects etc.
Compare with the administering mode of traditional oral formulations, exist essential distinction.With the drop pill of solid dispersion technology preparation, can adopt oral, can also sublingual administration, effective ingredient is fully contacted with mucomembranous surface, by the mucomembranous epithelial cell absorption, directly enter 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.
2. Xiyanping 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, and local application's onset is faster.
3. Xiyanping 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.
4. Xiyanping drop pill involved in the present invention, stable in properties; Than injection, it is not prone to anaphylaxis, and side effect is little.
In sum, make Xiyanping 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 Xiyanping drop pill of the present invention.
First group: the test of single-matrix
1. andrographolide sulfonated bodies;
2. substrate: Polyethylene Glycol
(1000～20000), 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 medicine: substrate=1: 1～1: 9;
4. be prepared according to the process of [preparation method] 4～7 again, promptly can make the Xiyanping drop pill of various different sizes.
[result of the test]
Test 1: for observe andrographolide sulfonated bodies and different substrates when 1: 1 the proportioning prepared Xiyanping drop pill in qualitative difference, according to 1: 1 ratio, with the andrographolide sulfonated bodies respectively with Polyethylene Glycol
1000, Polyethylene Glycol
4000, Polyethylene Glycol
6000, Polyethylene Glycol
8000, Polyethylene Glycol
9300, 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 andrographolide sulfonated bodies and different substrates, and obtain 15 groups of different experimental results and see Table 1.
Test 2: for observe andrographolide sulfonated bodies and different substrates when 1: 3 the proportioning prepared Xiyanping drop pill in qualitative difference, according to 1: 3 ratio, with the andrographolide sulfonated bodies respectively with Polyethylene Glycol
1000, Polyethylene Glycol
2000, Polyethylene Glycol
4000, Polyethylene Glycol
6000, Polyethylene Glycol
8000, Polyethylene Glycol
9300, Polyethylene Glycol
10000, pharmaceutically suitable carrier such as Macrogol 2000 0, 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 andrographolide sulfonated bodies and different substrates, and obtain 15 groups of different experimental results and see Table 2.
Test 3: for observe andrographolide sulfonated bodies and different substrates when 1: 9 the proportioning prepared Xiyanping drop pill in qualitative difference, according to 1: 9 ratio, with the andrographolide sulfonated bodies respectively with Polyethylene Glycol
1000, Polyethylene Glycol
2000, Polyethylene Glycol
4000, Polyethylene Glycol
6000, Polyethylene Glycol
8000, Polyethylene Glycol
9300, 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 andrographolide sulfonated bodies and different substrates, and obtain 15 groups of different experimental results and see Table 3.
Second group: the test of mixed-matrix
1. andrographolide sulfonated bodies;
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 1 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: mixed-matrix weight and=1: 1～1: 9.
4. be prepared according to the process of [preparation method] 4～7 again, promptly can make the Xiyanping drop pill of various different sizes.
[result of the test]
Test 4: for observe andrographolide sulfonated bodies and mixed-matrix when 1: 1 the proportioning prepared Xiyanping 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 the andrographolide sulfonated bodies 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 pharmaceutical composition experiment that 4 andrographolide sulfonated bodies and mixed-matrixes are constituted, and obtain 4 groups of different experimental results and see Table 4.
Test 5: for observe andrographolide sulfonated bodies and mixed-matrix when 1: 3 the proportioning prepared Xiyanping 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 the andrographolide sulfonated bodies 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 pharmaceutical composition experiment that 4 andrographolide sulfonated bodies and mixed-matrixes are constituted, and obtain 4 groups of different experimental results and see Table 5.
Test 6: for observe andrographolide sulfonated bodies and mixed-matrix when 1: 9 the proportioning prepared Xiyanping 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 the andrographolide sulfonated bodies 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 pharmaceutical composition experiment that 4 andrographolide sulfonated bodies and mixed-matrixes are constituted, and obtain 4 groups of different experimental results and see Table 6.
Test 7: for observe andrographolide sulfonated bodies and mixed-matrix when 1: 1 the proportioning prepared Xiyanping 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 the andrographolide sulfonated bodies 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 pharmaceutical composition experiment that 4 andrographolide sulfonated bodies and mixed-matrixes are constituted, and obtain 4 groups of different experimental results and see Table 7.
Test 8: for observe andrographolide sulfonated bodies and mixed-matrix when 1: 3 the proportioning prepared Xiyanping 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 the andrographolide sulfonated bodies 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 pharmaceutical composition experiment that 4 andrographolide sulfonated bodies and mixed-matrixes are constituted, and obtain 4 groups of different experimental results and see Table 8.
Test 9: for observe andrographolide sulfonated bodies and mixed-matrix when 1: 9 the proportioning prepared Xiyanping 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 the andrographolide sulfonated bodies 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 pharmaceutical composition experiment that 4 andrographolide sulfonated bodies and mixed-matrixes are constituted, and obtain 4 groups of different experimental results and see Table 9.
Test 10: in order to observe Xiyanping drop pill that andrographolide sulfonated bodies and mixed-matrix make when 1: 1 the proportioning 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 the andrographolide sulfonated bodies 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 pharmaceutical composition experiment that 4 andrographolide sulfonated bodies and mixed-matrixes are constituted, and obtain 4 groups of different experimental results and see Table 10.
Test 11: in order to observe Xiyanping drop pill that andrographolide sulfonated bodies and mixed-matrix make when 1: 3 the proportioning 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 the andrographolide sulfonated bodies 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 pharmaceutical composition experiment that 4 andrographolide sulfonated bodies and mixed-matrixes are constituted, and obtain 4 groups of different experimental results and see Table 11.
Test 12: in order to observe Xiyanping drop pill that andrographolide sulfonated bodies and mixed-matrix make when 1: 9 the proportioning 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 the andrographolide sulfonated bodies 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 pharmaceutical composition experiment that 4 andrographolide sulfonated bodies and mixed-matrixes are constituted, and obtain 4 groups of different experimental results and see Table 12.
The group practices of table 1 andrographolide sulfonated bodies and single-matrix
(andrographolide sulfonated bodies: 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 1000 | 50.0 | 70 | ＜30 | ＞10 | + |
| Polyethylene Glycol 2000 | 50.0 | 75 | ＜30 | ＞10 | + |
| Polyethylene Glycol 4000 | 50.0 | 76 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 6000 | 50.0 | 85 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 8000 | 50.0 | 79 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 9300 | 50.0 | 88 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 10000 | 50.0 | 82 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 20000 | 50.0 | 80 | ＜30 | ＞10 | ++ |
| Polyoxyethylene stearate 40 esters | 50.0 | 78 | ＜30 | ＞10 | ++ |
| Betacyclodextrin | 50.0 | 74 | ＜30 | ＞10 | + |
| Poloxamer | 50.0 | 80 | ＜30 | ＞10 | ++ |
| Carboxymethyl starch sodium | 50.0 | 73 | ＜30 | ＞10 | + |
| Sodium lauryl sulphate | 50.0 | 68 | ＞30 | ＞10 | ++ |
| Stearic acid | 50.0 | 55 | ＞30 | ＞10 | +++ |
| Sodium stearate | 50.0 | 54 | ＞30 | ＞10 | +++ |
| Glycerin gelatine | 50.0 | 55 | ＞30 | ＞10 | +++ |
| Lac | 50.0 | 52 | ＞30 | ＞10 | +++ |
The group practices of table 2 andrographolide sulfonated bodies and single-matrix
(andrographolide sulfonated bodies: 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 1000 | 25.0 | 77 | ＜30 | ＞10 | + |
| Polyethylene Glycol 2000 | 25.0 | 79 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 4000 | 25.0 | 86 | ＜30 | ＜10 | ++ |
| Polyethylene Glycol 6000 | 25.0 | 93 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 8000 | 25.0 | 93 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 9300 | 25.0 | 94 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 10000 | 25.0 | 94 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 20000 | 25.0 | 91 | ＜30 | ＜10 | ++ |
| Polyoxyethylene stearate 40 esters | 25.0 | 93 | ＜30 | ＜10 | ++ |
| Betacyclodextrin | 25.0 | 83 | ＜30 | ＞10 | ++ |
| Poloxamer | 25.0 | 89 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium | 25.0 | 79 | ＜30 | ＞10 | ++ |
| Sodium lauryl sulphate | 25.0 | 77 | ＜30 | ＞10 | ++ |
| Stearic acid | 25.0 | 73 | ＞30 | ＞10 | +++ |
| Sodium stearate | 25.0 | 72 | ＞30 | ＞10 | +++ |
| Glycerin gelatine | 25.0 | 71 | ＞30 | ＞10 | +++ |
| Lac | 25.0 | 72 | ＞30 | ＞10 | +++ |
The group practices of table 3 andrographolide sulfonated bodies and single-matrix
(andrographolide sulfonated bodies: 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 1000 | 10.0 | 77 | ＜30 | ＞10 | + |
| Polyethylene Glycol 2000 | 10.0 | 83 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 4000 | 10.0 | 93 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 6000 | 10.0 | 94 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 8000 | 10.0 | 92 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 9300 | 10.0 | 89 | ＜30 | ＞10 | +++ |
| Polyethylene Glycol 10000 | 10.0 | 93 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 20000 | 10.0 | 92 | ＜30 | ＜10 | +++ |
| Polyoxyethylene stearate 40 esters | 10.0 | 90 | ＜30 | ＜10 | ++ |
| Betacyclodextrin | 10.0 | 88 | ＜30 | ＜10 | ++ |
| Poloxamer | 10.0 | 92 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium | 10.0 | 86 | ＜30 | ＜10 | +++ |
| Sodium lauryl sulphate | 10.0 | 83 | ＜30 | ＞10 | +++ |
| Stearic acid | 10.0 | 76 | ＞30 | ＞10 | +++ |
| Sodium stearate | 10.0 | 77 | ＞30 | ＞10 | +++ |
| Glycerin gelatine | 10.0 | 74 | ＞30 | ＞10 | +++ |
| Lac | 10.0 | 73 | ＞30 | ＞10 | +++ |
The group practices of table 4 andrographolide sulfonated bodies and mixed-matrix
(andrographolide sulfonated bodies: 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 | 85 | ＜30 | ＜10 | ++ |
| Poloxamer: Polyethylene Glycol=1: 1 | 50 | 87 | ＜30 | ＜10 | ++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | 50 | 82 | ＜30 | ＞10 | ++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | 50 | 79 | ＜30 | ＞10 | + |
The group practices of table 5 andrographolide sulfonated bodies and mixed-matrix
(andrographolide sulfonated bodies: 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 | 93 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 1 | 25 | 94 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | 25 | 88 | ＜30 | ＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | 25 | 86 | ＜30 | ＞10 | ++ |
The group practices of table 6 andrographolide sulfonated bodies and mixed-matrix
(andrographolide sulfonated bodies: 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 | 92 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 1 | 10 | 93 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | 10 | 91 | ＜30 | ＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | 10 | 85 | ＜30 | ＞10 | +++ |
The group practices of table 7 andrographolide sulfonated bodies and mixed-matrix
(andrographolide sulfonated bodies: 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 | 95 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 5 | 50 | 94 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 5 | 50 | 90 | ＜30 | ＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | 50 | 83 | ＜30 | ＞10 | ++ |
The group practices of table 8 andrographolide sulfonated bodies and mixed-matrix
(andrographolide sulfonated bodies: 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 | 94 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 5 | 25 | 96 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 5 | 25 | 92 | ＜30 | ＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | 25 | 88 | ＜30 | ＜10 | ++ |
The group practices of table 9 andrographolide sulfonated bodies and mixed-matrix
(andrographolide sulfonated bodies: 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 | 95 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 5 | 10 | 94 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 5 | 10 | 91 | ＜30 | ＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | 10 | 88 | ＜30 | ＜10 | +++ |
The group practices of table 10 andrographolide sulfonated bodies and mixed-matrix
(andrographolide sulfonated bodies: 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 | 93 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 10 | 50 | 89 | ＜30 | ＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 10 | 50 | 82 | ＜30 | ＞10 | +++ |
The group practices of table 11 andrographolide sulfonated bodies and mixed-matrix
(andrographolide sulfonated bodies: mixed-matrix=1: 3)
The group practices of table 12 andrographolide sulfonated bodies and mixed-matrix
| 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 | 94 | ＜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 | +++ |
(andrographolide sulfonated bodies: 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 | 96 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 10 | 10 | 94 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 10 | 10 | 91 | ＜30 | ＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 10 | 10 | 90 | ＜30 | ＜10 | +++ |
1. can be seen by the result in the table: when the ratio of andrographolide sulfonated bodies 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 andrographolide sulfonated bodies 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 andrographolide sulfonated bodies 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 (3)
1. oral administration dripping pill that is used for the treatment of bronchitis, tonsillitis, bacillary dysentery, with the andrographolide sulfonated bodies is raw material, be prepared from a certain proportion of pharmaceutically suitable carrier, it is characterized in that: described carrier is the mixture of cetomacrogol 1000～Macrogol 2000 0 and poloxamer, with g or kg is unit, by weight, the ratio of poloxamer and Polyethylene Glycol is 1: 5, and the ratio of andrographolide sulfonated bodies and above-mentioned mixed carrier is 1: 3.
2. one kind is the method for feedstock production drop pill with the andrographolide sulfonated bodies, it is characterized in that being made of following process:
(1) by weight, it is standby to take by weighing andrographolide sulfonated bodies, poloxamer and Polyethylene Glycol with 2: 1: 5 ratio;
(2) with above-mentioned raw materials and carrier mix homogeneously, place heating while stirring in the heating container, standby until obtaining containing fused solution and/or emulsion and/or suspension;
(3) temperature control system of adjustment drop pill machine makes the water dropper heating of drop pill machine and maintains the temperature at 50 ℃～90 ℃, and the condensing agent cooling also maintains the temperature at-5 ℃～40 ℃;
(4) temperature for the treatment of dropping-pill machine head and condensing agent is stable respectively when being in above-mentioned state, will above-mentioned fused medicinal liquid insulation, place in the water dropper jar of drop pill machine, and splash in the condensing agent and shrink shaping promptly.
3. as being the method for feedstock production drop pill as described in the claim 2, it is characterized in that with the andrographolide sulfonated bodies: described condensing agent be methyl-silicone oil or/and liquid paraffin or/and vegetable oil.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1349986A (en) * | 2001-10-24 | 2002-05-22 | 唐春山 | Sulfonation process of water soluble andrographolide |
| CN1444937A (en) * | 2003-04-21 | 2003-10-01 | 南昌弘益科技有限公司 | Drop pills of andrographolide and its preparing method |
| CN1552313A (en) * | 2003-12-19 | 2004-12-08 | 北京正大绿洲医药科技有限公司 | Process for preparing drops or other drop agents |
-
2004
- 2004-12-31 CN CNB2004101040430A patent/CN1301107C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1349986A (en) * | 2001-10-24 | 2002-05-22 | 唐春山 | Sulfonation process of water soluble andrographolide |
| CN1444937A (en) * | 2003-04-21 | 2003-10-01 | 南昌弘益科技有限公司 | Drop pills of andrographolide and its preparing method |
| CN1552313A (en) * | 2003-12-19 | 2004-12-08 | 北京正大绿洲医药科技有限公司 | Process for preparing drops or other drop agents |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1660077A (en) | 2005-08-31 |
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