CN1686120A - Hydrobromic acid high tortoiseshell component drip pill and its preparation method - Google Patents
Hydrobromic acid high tortoiseshell component drip pill and its preparation method Download PDFInfo
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- CN1686120A CN1686120A CN 200510064499 CN200510064499A CN1686120A CN 1686120 A CN1686120 A CN 1686120A CN 200510064499 CN200510064499 CN 200510064499 CN 200510064499 A CN200510064499 A CN 200510064499A CN 1686120 A CN1686120 A CN 1686120A
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Abstract
A dripping pill of sinomontanine A hydrobromate for treating pain and swelling, local anesthesia, cooling, and antipyresis is prepared from the sinomontanine A hydrobromate and pharmacologically acceptable carrier.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition with analgesia, local anesthesia, cooling, analgesic and detumescence effect, particularly is a kind of drug composition oral preparation that feedstock production forms with the lappaconitine hydrobromide.
Background technology
The lappaconitine hydrobromide sheet is to be a kind of oral formulations that feedstock production forms with the lappaconitine hydrobromide, has analgesia and local anesthesia, cooling, analgesic and detumescence effect, is used for the treatment of intractable pain, particularly cancer pain.Owing to can improve patient's General Symptoms, the human body immunity improving index, can be used as the operation analgesic and put, the chemotherapy adjuvant, chronic pain (as gastroenteritic ulcer, gastritis, hepatitis, cholecystitis, pulmonary tuberculosis, rheumatic arthritis, sciatica, postoperative pain etc.), and to flu good analgesia also arranged, bring down a fever, the oral tablet of antiinflammation, through clinical verification, determined curative effect is the common drug that clinical and family is used for the treatment of this type of disease.
Below be the partial content that lappaconitine hydrobromide flake products description is provided:
Lappaconitine hydrobromide sheet description
Common name: lappaconitine hydrobromide sheet
English name: Lappaconitine Hydrobromide Tablets
The Chinese phonetic alphabet: Qingxiusuan Gaowujiasu Pian
Main Ingredients and Appearance: lappaconitine hydrobromide
Chemical name: (10 α, 14 α, 16 β)-20-ethyl-1,14,16-trimethoxy aconitane-4,8,9-triol 4-[2-(acetylamino) benzoate hydrobromate sulfuric monohydrate.
Molecular formula: C
32H
44N
2O
8HBrH
2O
Molecular weight: 683.64
Character: this crystalline substance is a coated tablet, removes whitening color behind the sugar-coat
The pharmacology: this product is non-addicted analgesics, has stronger analgesic activity.This crystalline substance also has local anesthesia, cooling, analgesic and antiinflammatory action.It is suitable that this product and Pethidine are compared analgesic effect, and onset time is slow slightly, and it is longer to hold time; Analgesic activity is 7 times of antipyretic analgesic aminophenazone.
Indication: be used for the above pain of moderate.
(reference material: lappaconitine hydrobromide sheet description. the 4th the 37th page of chemical drugs description)
Owing to reasons such as technologies of preparing, the oral formulations of most drug, exist all after taking that dissolve scattered time limit is long, dissolution is low, absorption is relatively poor, problem such as liver sausage first pass effect and bioavailability are lower, thereby influence the performance of drug effect, also directly affect therapeutic effect.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 deficiency that is used for the treatment of the oral drug preparation of the above pain of moderate, and a kind of bioavailability height is provided, and has a quick release, produce effects is cheap fast, and free of contamination aborning drug composition oral preparation hydrobromic acid high tortoiseshell component drip pill.Hydrobromic acid high tortoiseshell component drip pill involved in the present invention is a raw material with the lappaconitine hydrobromide, is prepared from the pharmaceutically suitable carrier as substrate.
Be prepared by the following technical solutions, can obtain hydrobromic acid high tortoiseshell component drip pill involved in the present invention:
[preparation method]
1. lappaconitine hydrobromide:
English name: Lappaconitine Hydrobromide Tablets
Chemical name: (10 α, 14 α, 16 β)-20-ethyl-1,14,16-trimethoxy aconitane-4,8,9-triol 4-[2-(acetylamino) benzoate hydrobromate sulfuric monohydrate.
Molecular formula: C
32H
44N
2O
8HBrH
2O
Molecular weight: 683.64
Chemical structural formula:
2. substrate: the mixture of one or more in pharmaceutically suitable carrier such as polyethylene glycols, sorbitol anhydride class, polyoxyethylene sorbitol acid anhydride class, 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 lappaconitine hydrobromide: substrate=1: 1～1: 9;
4. according to the given ratio of prescription, accurately take by weighing lappaconitine hydrobromide and substrate, be placed on heating while stirring in the heating container, standby until the fused solution that obtains containing medicine dry powder 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. when treating that the temperature of condensing agent in dropping-pill machine head and the condensation column is stable respectively and reaching desired state of temperature, fused solution and/or the emulsion and/or the suspension that will contain lappaconitine hydrobromide and substrate, place in the water dropper jar of drop pill machine, splash in the condensing agent, condensing agent can be any one in liquid paraffin, methyl-silicone oil, the vegetable oil;
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]
The lappaconitine hydrobromide sheet is to be a kind of oral formulations that feedstock production forms with the lappaconitine hydrobromide, has analgesia and local anesthesia, cooling, analgesic and detumescence effect, is used for the treatment of intractable pain, particularly cancer pain.Owing to can improve patient's General Symptoms, the human body immunity improving index, can be used as the operation analgesic and put, the chemotherapy adjuvant, chronic pain (as gastroenteritic ulcer, gastritis, hepatitis, cholecystitis, pulmonary tuberculosis, rheumatic arthritis, sciatica, postoperative pain etc.), and to flu good analgesia also arranged, bring down a fever, the oral tablet of antiinflammation, through clinical verification, determined curative effect is the common drug that clinical and family is used for the treatment of this type of disease.
Owing to reasons such as technologies of preparing, the oral formulations of most drug, exist all after taking that dissolve scattered time limit is long, dissolution is low, absorption is relatively poor, problem such as liver sausage first pass effect and bioavailability are lower, thereby influence the performance of drug effect, also directly affect therapeutic effect.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.
Hydrobromic acid high tortoiseshell component drip pill involved in the present invention is compared with the lappaconitine hydrobromide sheet has following beneficial effect:
1. hydrobromic acid high tortoiseshell component drip pill involved in the present invention; utilize surfactant to be substrate; make solid dispersion with lappaconitine hydrobromide, 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.
2. hydrobromic acid high tortoiseshell component drip pill involved in the present invention, contact promptly with saliva and to dissolve rapidly, and absorb by oral mucosa, not only rapid-action, and the influence of not taken food, promptly all can containing take after meal ante cibum, can not produce any residual harmful substance at gastric yet, thereby make that patient's medication is safer, also have medication convenience, characteristic of accurate simultaneously.
3. hydrobromic acid high tortoiseshell component drip pill involved in the present invention mixes lappaconitine hydrobromide mutually with molten matrix, splashes in the not miscible condensed fluid to make.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. production technology, the equipment of preparation drop pill are simple, easy to operate, the automaticity height, and labor intensity is low, the production efficiency height.Workshop does not have dust simultaneously, helps labor protection and environmental protection yet.
5. the production cost of preparation drop pill is usually with about 50% of other oral formulations of kind, and compares with oral liquid, and the dosage of drop pill is accurate, thereby makes the patient take metering control easily.
The specific embodiment
Now with several groups of specific embodiments, be described further with regard to the preparation method of hydrobromic acid high tortoiseshell component drip pill of the present invention.
[first group: the test of single-matrix]
1. lappaconitine hydrobromide:
English name: Lappaconitine Hydrobromide Tablets
Chemical name: (10 α, 14 α, 16 β)-20-ethyl-1,14,16-trimethoxy aconitane-4,8,9-triol 4-[2-(acetylamino) benzoate hydrobromate sulfuric monohydrate.
2. substrate: Polyethylene Glycol
1000, Polyethylene Glycol
4000, Polyethylene Glycol
6000, Polyethylene Glycol
10000, Polyethylene Glycol
20000, span 40, polyoxyethylene stearate 40 esters, poloxamer, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac;
3. proportioning: with g or kg is unit, by weight, and lappaconitine hydrobromide: substrate=1: 1～1: 9;
4. the process according to [preparation method] 4～7 is prepared, and can obtain the hydrobromic acid high tortoiseshell component drip pill of different size.
[result of the test]
Test 1: for observe lappaconitine hydrobromide and different substrates when 1: 1 the proportioning prepared hydrobromic acid high tortoiseshell component drip pill in qualitative difference, according to 1: 1 ratio, with lappaconitine hydrobromide respectively with Polyethylene Glycol
1000, Polyethylene Glycol
4000, Polyethylene Glycol
6000, Polyethylene Glycol
10000, Polyethylene Glycol
20000, pharmaceutically suitable carrier such as span 40, polyoxyethylene stearate 40 esters, poloxamer, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac matches, be prepared according to the step of stipulating in the preparation method, can obtain 16 pharmaceutical compositions experiments that contain lappaconitine hydrobromide and different substrates, and obtain 16 groups of different experimental results and see Table 1.
Test 2: for observe lappaconitine hydrobromide and different substrates when 1: 3 the proportioning prepared hydrobromic acid high tortoiseshell component drip pill in qualitative difference, according to 1: 3 ratio, with lappaconitine hydrobromide respectively with Polyethylene Glycol
1000, Polyethylene Glycol
4000, Polyethylene Glycol
6000, Polyethylene Glycol
10000, Polyethylene Glycol
20000, pharmaceutically suitable carrier such as span 40, polyoxyethylene stearate 40 esters, poloxamer, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac matches, be prepared according to the step of stipulating in the preparation method, can obtain 16 pharmaceutical compositions experiments that contain lappaconitine hydrobromide and different substrates, and obtain 16 groups of different experimental results and see Table 2.
Test 3: for observe lappaconitine hydrobromide and different substrates when 1: 9 the proportioning prepared hydrobromic acid high tortoiseshell component drip pill in qualitative difference, according to 1: 9 ratio, with lappaconitine hydrobromide respectively with Polyethylene Glycol
1000, Polyethylene Glycol
4000, Polyethylene Glycol
6000, Polyethylene Glycol
10000, Polyethylene Glycol
20000, pharmaceutically suitable carrier such as span 40, polyoxyethylene stearate 40 esters, poloxamer, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac matches, be prepared according to the step of stipulating in the preparation method, can obtain 16 pharmaceutical compositions experiments that contain lappaconitine hydrobromide and different substrates, and obtain 16 groups of different experimental results and see Table 3.
Second group: the test of mixed-matrix
1. lappaconitine hydrobromide:
English name: Lappaconitine Hydrobromide Tablets
Chemical name: (10 α, 14 α, 16 β)-20-ethyl-1,14,16-trimethoxy aconitane-4,8,9-triol 4-[2-(acetylamino) benzoate hydrobromate sulfuric monohydrate.
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. proportioning: with g or kg is unit, by weight, and lappaconitine hydrobromide: substrate=1: 1～1: 9;
4. the process that provides according to [preparation method] 4～7 is prepared, and can obtain the different size hydrobromic acid high tortoiseshell component drip pill.
[result of the test]
Test 4: in order to observe the mass discrepancy of lappaconitine hydrobromide and mixed-matrix prepared hydrobromic acid high tortoiseshell component drip pill when 1: 1 the proportioning, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 1 mixed evenly as mixed-matrix, according to 1: 1 ratio different with the 4 kinds respectively mixing matrix phases of lappaconitine hydrobromide are mixed again and make evenly, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that lappaconitine hydrobromide and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 4.
Test 5: in order to observe the mass discrepancy of lappaconitine hydrobromide and mixed-matrix prepared hydrobromic acid high tortoiseshell component drip pill when 1: 3 the proportioning, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 1 mixed evenly as mixed-matrix, according to 1: 3 ratio different with the 4 kinds respectively mixing matrix phases of lappaconitine hydrobromide are mixed again and make evenly, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that lappaconitine hydrobromide and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 5.
Test 6: in order to observe the mass discrepancy of lappaconitine hydrobromide and mixed-matrix prepared hydrobromic acid high tortoiseshell component drip pill when 1: 9 the proportioning, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 1 mixed evenly as mixed-matrix, according to 1: 9 ratio different with the 4 kinds respectively mixing matrix phases of lappaconitine hydrobromide are mixed again and make evenly, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that lappaconitine hydrobromide and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 6.
Test 7: in order to observe the mass discrepancy of lappaconitine hydrobromide and mixed-matrix prepared hydrobromic acid high tortoiseshell component drip pill when 1: 1 the proportioning, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 5 mixed evenly as mixed-matrix, according to 1: 1 ratio different with the 4 kinds respectively mixing matrix phases of lappaconitine hydrobromide are mixed again and make evenly, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that lappaconitine hydrobromide and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 7.
Test 8: in order to observe the mass discrepancy of lappaconitine hydrobromide and mixed-matrix prepared hydrobromic acid high tortoiseshell component drip pill when 1: 3 the proportioning, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 5 mixed evenly as mixed-matrix, according to 1: 3 ratio different with the 4 kinds respectively mixing matrix phases of lappaconitine hydrobromide are mixed again and make evenly, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that lappaconitine hydrobromide and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 8.
Test 9: in order to observe the mass discrepancy of lappaconitine hydrobromide and mixed-matrix prepared hydrobromic acid high tortoiseshell component drip pill when 1: 9 the proportioning, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 5 mixed evenly as mixed-matrix, according to 1: 9 ratio different with the 4 kinds respectively mixing matrix phases of lappaconitine hydrobromide are mixed again and make evenly, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that lappaconitine hydrobromide and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 9.
Test 10: in order to observe the mass discrepancy of lappaconitine hydrobromide and mixed-matrix prepared hydrobromic acid high tortoiseshell component drip pill when 1: 1 the proportioning, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 10 mixed evenly as mixed-matrix, according to 1: 1 ratio lappaconitine hydrobromide is mixed mutually with 4 kinds of different mixed-matrixes respectively again and make evenly, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that lappaconitine hydrobromide and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 10.
Test 11: in order to observe the mass discrepancy of lappaconitine hydrobromide and mixed-matrix prepared hydrobromic acid high tortoiseshell component drip pill when 1: 3 the proportioning, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 10 mixed evenly as mixed-matrix, according to 1: 3 ratio lappaconitine hydrobromide is mixed mutually with 4 kinds of different mixed-matrixes respectively again and make evenly, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that lappaconitine hydrobromide and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 11.
Test 12: in order to observe the mass discrepancy of lappaconitine hydrobromide and mixed-matrix prepared hydrobromic acid high tortoiseshell component drip pill when 1: 9 the proportioning, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 10 mixed evenly as mixed-matrix, according to 1: 9 ratio lappaconitine hydrobromide is mixed mutually with 4 kinds of different mixed-matrixes respectively again and make evenly, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that lappaconitine hydrobromide and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 12.
The group practices of table 1 lappaconitine hydrobromide and single-matrix
(lappaconitine hydrobromide: 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 | ????63 | ????＜30 | ????＞10 | + |
| Polyethylene Glycol 4000 | ????50.0 | ????86 | ????＜30 | ????＜10 | + |
| Polyethylene Glycol 6000 | ????50.0 | ????86 | ????＜30 | ????＜10 | + |
| Polyethylene Glycol 10000 | ????50.0 | ????87 | ????＜30 | ????＜10 | ++ |
| Polyethylene Glycol 20000 | ????50.0 | ????87 | ????＜30 | ????＜10 | ++ |
| Span 40 | ????50.0 | ????61 | ????＜30 | ????＞10 | + |
| Polyoxyethylene stearate 40 esters | ????50.0 | ????84 | ????＜30 | ????＞10 | ++ |
| Poloxamer | ????50.0 | ????84 | ????＜30 | ????＞10 | ++ |
| Sodium lauryl sulphate | ????50.0 | ????76 | ????＜30 | ????＞10 | ++ |
| Stearic acid | ????50.0 | ????64 | ????＞30 | ????＞10 | ++ |
| Sodium stearate | ????50.0 | ????62 | ????＞30 | ????＞10 | ++ |
| Glycerin gelatine | ????50.0 | ????60 | ????＞30 | ????＞10 | + |
| Lac | ????50.0 | ????60 | ????＞30 | ????＞10 | + |
The group practices of table 2 lappaconitine hydrobromide and single-matrix
(lappaconitine hydrobromide: 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 | ????73 | ????＜30 | ????＞10 | ++ |
| Polyethylene Glycol 4000 | ????25.0 | ????89 | ????＜30 | ????＜10 | ++ |
| Polyethylene Glycol 6000 | ????25.0 | ????89 | ????＜30 | ????＜10 | +++ |
| Polyethylene Glycol 10000 | ????25.0 | ????90 | ????＜30 | ????＜10 | +++ |
| Polyethylene Glycol 20000 | ????25.0 | ????90 | ????＜30 | ????＜10 | +++ |
| Span 40 | ????25.0 | ????73 | ????＜30 | ????＞10 | +++ |
| Polyoxyethylene stearate 40 esters | ????25.0 | ????92 | ????＜30 | ????＜10 | +++ |
| Poloxamer | ????25.0 | ????92 | ????＜30 | ????＜10 | ++ |
| Sodium lauryl sulphate | ????25.0 | ????84 | ????＜30 | ????＞10 | ++ |
| Stearic acid | ????25.0 | ????78 | ????＞30 | ????＞10 | +++ |
| Sodium stearate | ????25.0 | ????78 | ????＞30 | ????＞10 | +++ |
| Glycerin gelatine | ????25.0 | ????67 | ????＞30 | ????＞10 | +++ |
| Lac | ????25.0 | ????67 | ????＞30 | ????＞10 | +++ |
The group practices of table 3 lappaconitine hydrobromide and single-matrix
(lappaconitine hydrobromide: 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 | ????79 | ????＜30 | ????＞10 | ++ |
| Polyethylene Glycol 4000 | ????10.0 | ????90 | ????＜30 | ????＞10 | ++ |
| Polyethylene Glycol 6000 | ????10.0 | ????90 | ????＜30 | ????＜10 | +++ |
| Polyethylene Glycol 10000 | ????10.0 | ????90 | ????＜30 | ????＜10 | +++ |
| Polyethylene Glycol 20000 | ????10.0 | ????91 | ????＜30 | ????＜10 | +++ |
| Span 40 | ????10.0 | ????76 | ????＜30 | ????＞10 | ++ |
| Polyoxyethylene stearate 40 esters | ????10.0 | ????90 | ????＜30 | ????＜10 | ++ |
| Poloxamer | ????10.0 | ????90 | ????＜30 | ????＜10 | +++ |
| Sodium lauryl sulphate | ????10.0 | ????83 | ????＜30 | ????＞10 | +++ |
| Stearic acid | ????10.0 | ????82 | ????＞30 | ????＞10 | +++ |
| Sodium stearate | ????10.0 | ????80 | ????＞30 | ????＞10 | +++ |
| Glycerin gelatine | ????10.0 | ????76 | ????＞30 | ????＞10 | +++ |
| Lac | ????10.0 | ????75 | ????＞30 | ????＞10 | +++ |
The group practices of table 4 lappaconitine hydrobromide and mixed-matrix
(lappaconitine hydrobromide: mixed-matrix=1: 1)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 1 | ????50 | ????84 | ????＜30 | ????＞10 | ++ |
| Poloxamer: Polyethylene Glycol=1: 1 | ????50 | ????83 | ????＜30 | ????＞10 | ++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | ????50 | ????82 | ????＜30 | ????＞10 | ++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | ????50 | ????80 | ????＜30 | ????＞10 | + |
The group practices of table 5 lappaconitine hydrobromide and mixed-matrix
(lappaconitine hydrobromide: mixed-matrix=1: 3)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 1 | ????25 | ????87 | ????＜30 | ????＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 1 | ????25 | ????87 | ????＜30 | ????＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | ????25 | ????84 | ????＜30 | ????＞10 | ++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | ????25 | ????84 | ????＜30 | ????＞10 | ++ |
The group practices of table 6 lappaconitine hydrobromide and mixed-matrix
(oxygen bromic acid lappaconitine: 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 | ????90 | ????＜30 | ????＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 1 | ????10 | ????90 | ????＜30 | ????＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | ????10 | ????88 | ????＜30 | ????＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | ????10 | ????87 | ????＜30 | ????＞10 | +++ |
The group practices of table 7 lappaconitine hydrobromide and mixed-matrix
(lappaconitine hydrobromide: 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 | ????91 | ????＜30 | ????＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 5 | ????50 | ????89 | ????＜30 | ????＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | ????50 | ????89 | ????＜30 | ????＜10 | ++ |
The group practices of table 8 lappaconitine hydrobromide and mixed-matrix
(lappaconitine hydrobromide: 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 | ????91 | ????＜30 | ????＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | ????25 | ????90 | ????＜30 | ????＜10 | +++ |
The group practices of table 9 lappaconitine hydrobromide and mixed-matrix
(lappaconitine hydrobromide: 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 | ????91 | ????＜30 | ????＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 5 | ????10 | ????92 | ????＜30 | ????＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 5 | ????10 | ????92 | ????＜30 | ????＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | ????10 | ????88 | ????＜30 | ????＜10 | +++ |
The group practices of table 10 lappaconitine hydrobromide and mixed-matrix
(lappaconitine hydrobromide: 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 | ????89 | ????＜30 | ????＞10 | +++ |
The group practices of table 11 lappaconitine hydrobromide and mixed-matrix
(lappaconitine hydrobromide: mixed-matrix=1: 3)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 10 | ????25 | ????91 | ????＜30 | ????＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 10 | ????25 | ????92 | ????＜30 | ????＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 10 | ????25 | ????90 | ????＜30 | ????＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 10 | ????25 | ????91 | ????＜30 | ????＜10 | +++ |
The group practices of table 12 lappaconitine hydrobromide and mixed-matrix
(lappaconitine hydrobromide: 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 | ????91 | ????＜30 | ????＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 10 | ????10 | ????91 | ????＜30 | ????＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 10 | ????10 | ????91 | ????＜30 | ????＜10 | +++ |
1. can be seen by the result in the table: when the ratio of lappaconitine hydrobromide 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 lappaconitine hydrobromide 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 lappaconitine hydrobromide and substrate is 1: 9, the rounding rate, the ball method of double differences is different and index such as hardness improves not obvious.
4. the general effect of composite interstitial substance is better than single-matrix.
5. the hardness method for expressing in the subordinate list adopts drop pill is placed on the glass plate, press...withes one's finger it, observes its metamorphosis."+" expression flicking promptly is out of shape, " ++ " expression distortion of firmly pressing, and " +++" expression is indeformable by it.
Claims (5)
1. the pharmaceutical composition hydrobromic acid high tortoiseshell component drip pill with analgesia, local anesthesia, cooling, analgesic and detumescence effect is a raw material with the lappaconitine hydrobromide, be prepared from pharmaceutically suitable carrier as substrate, wherein:
1.1 substrate: the mixture of one or more in pharmaceutically suitable carrier such as polyethylene glycols, sorbitol anhydride class, polyoxyethylene sorbitol acid anhydride class, polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac;
1.2 proportioning: with g or kg is unit, by weight, and lappaconitine hydrobromide: substrate=1: 1～1: 9.
2. hydrobromic acid high tortoiseshell component drip 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 hydrobromic acid high tortoiseshell component drip pill as claimed in claim 1 or 2 is characterized in that: the mixed proportion of described medicine dry powder and substrate is 1: 1～1: 5.
4. the preparation method of a hydrobromic acid high tortoiseshell component drip pill is characterized in that being made of following process:
4.1 raw material: lappaconitine hydrobromide
4.2 substrate: the mixture of one or more in pharmaceutically suitable carrier such as polyethylene glycols, sorbitol anhydride class, polyoxyethylene sorbitol acid anhydride class, polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac;
4.3 proportioning: with g or kg is unit, by weight, and lappaconitine hydrobromide: substrate=1: 1～1: 9;
4.4, accurately take by weighing lappaconitine hydrobromide 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 lappaconitine hydrobromide and substrate and/or emulsion and/or suspension;
4.5 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 40 ℃～-5 ℃;
4.6 when treating in dropping-pill machine head and the condensation column that the temperature of condensing agent reaches desired state of temperature respectively, to contain the fused solution of lappaconitine hydrobromide and substrate and/or emulsion and/or suspension places in the water dropper jar of drop pill machine, splash in the condensing agent, shrink molding promptly.
5. as the preparation method of hydrobromic acid high tortoiseshell component drip pill as described in the claim 4, it is characterized in that: described condensing agent be methyl-silicone oil or/and liquid paraffin or/and vegetable oil.
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| CN100518721C (en) * | 2006-08-08 | 2009-07-29 | 云南昊邦制药有限公司 | Enteric quick-dissolving tablets containing aconitine, and preparation method thereof |
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| CN1074117A (en) * | 1992-01-10 | 1993-07-14 | 福州金山制药厂 | The prescription of " Gaowujiasu " picking and method for making |
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| CN100518721C (en) * | 2006-08-08 | 2009-07-29 | 云南昊邦制药有限公司 | Enteric quick-dissolving tablets containing aconitine, and preparation method thereof |
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