CN100358562C - Tendril-leaved fritillary bulb loquat drop pills and preparation method thereof - Google Patents
Tendril-leaved fritillary bulb loquat drop pills and preparation method thereof Download PDFInfo
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Abstract
The present invention discloses a medicinal composition which has the functions for clearing heat, freeing the lung, eliminating phlegm and stopping coughs and is used for treating the symptoms of cough with yellow phlegm or ungratifying ejection of phlegm, swelling pain in the throat, swelling pain in the chest, cold, cough, chronic bronchitis and the like caused by invasion of the lung by wind-heat, internal depression and fire generation. The present invention aims to overcome the defects of the existing oral medicine preparation for treating for treating the symptoms of cough with yellow phlegm or ungratifying ejection of phlegm, swelling pain in the throat, swelling pain in the chest, cold, cough, chronic bronchitis and the like caused by invasion of the lung by wind-heat, internal depression and fire generation and to provide a medicinal oral composition preparation, namely a bulbus fritilariae and loquat drop pill. The bulbus fritilariae and loquat drop pill has the advantages of high bioavailability, quick medicine release, high effectual speed, low toxic and side effect, high medicine content, low and accurate administration dose, convenient administration, low price and portability for outgoing.
Description
Technical field
The present invention relates to a kind of reducing heat and dispersing lung-QI that has, the preventing phlegm from forming and stopping coughing effect, be used for the treatment of wind-heat invading the lung, cough expectorant Huang or ungratifying ejection of phlegm due to the stagnation of fire in the interior, laryngopharynx swelling and pain, breast distending pain, the pharmaceutical composition of symptoms such as cold cough and chronic bronchitis, be particularly related to based on the Chinese traditional patent formulation Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae, change a social system a kind of drug composition oral dropping pill formulation that forms through dosage form.
Background technology
The Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae that is prepared from according to the prescription that provides among the drug standard WS-11408 promulgated by the ministries or commissions of the Central Government (ZD-1408)-2002 and extraction process, it is the treatment wind-heat invading the lung, cough expectorant Huang or ungratifying ejection of phlegm due to the stagnation of fire in the interior, laryngopharynx swelling and pain, breast distending pain, the oral syrup class pure Chinese medicinal preparation of symptoms such as cold cough and chronic bronchitis, 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.Other similar oral formulations also has the watered pill, tablet etc., and its characteristics are similar, act on basic identical, no significant difference.
Below be the prescription and the extraction process of the Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae that provides among the drug standard WS-11408 (ZD-1408)-2002:
Prescription: Bulbus Fritillariae Cirrhosae fluidextract 45ml, Radix Platycodonis 45g, Folium Eriobotryae 300g, Mentholum 0.34g, sucrose 400g, sodium benzoate 3g, almond essence 0.5ml
Method for making: above four Chinese medicine material, Bulbus Fritillariae Cirrhosae powder is broken into coarse powder, according to (appendix IO of Chinese Pharmacopoeia version in 2000) percolation under fluid extract and the extractum item, make solvent with 70% ethanol, flood after 5 days, slowly percolation, collect the liquid 38ml that just filters, device is preserved in addition, continues percolation, the soluble component of waiting is filtered out fully, and the continuous liquid of filtering is concentrated in right amount, adds the liquid of just filtering, mix, continue to be concentrated into 45ml, filter, standby; Radix Platycodonis, loquat leaf decoct with water secondary, and 2.5 hours for the first time, 2 hours for the second time, collecting decoction filters, and filtrate is concentrated in right amount, add sucrose and sodium benzoate, boil and make dissolving, filter, filtrate is mixed with Bulbus Fritillariae Cirrhosae fluidextract, put coldly, add the alcoholic solution of Mentholum and almond essence, add water to ormal weight, stir evenly, promptly.
Be explained as follows for this syrup in the appended Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae description:
Nomenclature of drug: Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae;
Main component: Bulbus Fritillariae Cirrhosae fluidextract, Radix Platycodonis, Folium Eriobotryae, Mentholum;
Character: this product is the brownish red thick liquid; Gas perfume (or spice), sweet, the little hardship of flavor, cold;
Function cures mainly: reducing heat and dispersing lung-QI, preventing phlegm from forming and stopping coughing.Be used for wind-heat invading the lung, cough expectorant Huang or ungratifying ejection of phlegm due to the stagnation of fire in the interior, laryngopharynx swelling and pain, the breast distending pain, cold cough and chronic bronchitis are seen above-mentioned disease person;
Usage and dosage: oral, a 10ml, 3 times on the one;
Writing out a prescription with this is that the fritillary-loquat oral formulations that make on the basis also has granule, tablet etc., and its therapeutical effect is 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.And that the syrups preparation also exists medicament contg is low, and taking dose is big, and taking dose is inaccurate, takes inconvenient characteristics, also is not easy to go out to carry wait deficiency.
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 wind-heat invading the lung that is used for the treatment of, cough expectorant Huang or ungratifying ejection of phlegm due to the stagnation of fire in the interior, laryngopharynx swelling and pain, breast distending pain, the deficiency of the oral drug preparation of symptoms such as cold cough and chronic bronchitis, provide a kind of bioavailability height, release fast, produce effects fast, toxic and side effects is littler, and the medicament contg height, and taking dose is little, and taking dose is accurate, taking convenience, cheap, and be convenient to the drug composition oral preparation tendril-leaved fritillary bulb loquat drop pills of going out to carry.
Tendril-leaved fritillary bulb loquat drop pills involved in the present invention determines that through a large amount of experiment sievings based on the extraction process of Chinese traditional patent formulation Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae, 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 tendril-leaved fritillary bulb loquat drop pills involved in the present invention:
[preparation method]
1. be unit with g or kg, calculate according to weight, Bulbus Fritillariae Cirrhosae fluidextract 12.5%, Radix Platycodonis 11.4%, Folium Eriobotryae 76%, Mentholum 1%, more than four flavors make the drug extract thick paste or dry powder standby;
2. substrate---Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), one or more the mixture in pharmaceutically suitable carrier such as polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac;
3. proportioning---with g or kg is unit, by weight, and drug extract: substrate=1: 1～1: 9.
4. according to the given ratio of prescription, accurately take by weighing drug extract and substrate, be placed on heating while stirring in the heating container, standby until the fused solution that obtains containing drug extract and substrate and/or emulsion and/or suspension;
5. adopt homemade or general drop pill machine (as the TZDW-1 type drop pill machine of Changzheng Tianmin High Science ﹠ Technology Co., Ltd., Beijing's production), and the temperature control system of adjustment drop pill machine, make the water dropper temperature heating of drop pill machine and remain on (50～90) ℃, the temperature cooling of condensing agent also remains on (40～-5) ℃;
6. treating that the temperature of condensing agent in dropping-pill machine head and the condensation column is stable respectively is in above the 2nd step during desired state of temperature, the Mentholum adding is contained 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;
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.
8. in method 1, also can add an amount of almond essence, as correctives.
[appendix 1: the preparation method of Bulbus Fritillariae Cirrhosae fluidextract]
Get the some coarse powder that are ground into of Bulbus Fritillariae Cirrhosae, ooze method, make solvent with 70% ethanol according to (appendix IO of Chinese Pharmacopoeia version in 2000) under fluid extract and the extractum item, flood after 5 days, slowly percolation is collected the liquid of just filtering, device is preserved in addition, continue percolation, the soluble component of waiting is filtered out fully, and the continuous liquid of filtering is concentrated in right amount, add the liquid of just filtering, mix, continue to be concentrated into relative density under 60 ℃ and be 1.1～1.2 thick paste, promptly.
[appendix 2: the preparation method of Chinese medicine extract]
Radix Platycodonis, loquat leaf are decocted with water secondary, and 2.5 hours for the first time, 2 hours for the second time, collecting decoction filtered, and it is 1.3～1.4 that 60 ℃ of following filtrates are concentrated into relative density, adds above-mentioned fluid extract, put coldly, added Mentholum and stirred and make evenly, promptly; Or pass through cold drying, pulverizing again, make into dry powder promptly.
[appendix 1: the preparation method of Bulbus Fritillariae Cirrhosae fluidextract] that provides above and [appendix 1: the preparation method of Bulbus Fritillariae Cirrhosae fluidextract] are that the preparation method change of basis a kind of fluid extract comparatively commonly used and Chinese medicine extract forms, similarly method is a lot, is not limited to this a kind of method during actual enforcement.
Beneficial effect
The Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae that is prepared from according to the prescription that provides among the drug standard WS-11408 promulgated by the ministries or commissions of the Central Government (ZD-1408)-2002 and extraction process, it is the treatment wind-heat invading the lung, cough expectorant Huang or ungratifying ejection of phlegm due to the stagnation of fire in the interior, laryngopharynx swelling and pain, breast distending pain, the oral syrup class pure Chinese medicinal preparation of symptoms such as cold cough and chronic bronchitis, 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.Other similar oral formulations also has the watered pill, tablet etc., and its characteristics are similar, act on basic identical, no significant difference.
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.And that the syrups preparation also exists medicament contg is low, and taking dose is big, and taking dose is inaccurate, takes inconvenient characteristics, also is not easy to go out to carry wait deficiency.
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.
Tendril-leaved fritillary bulb loquat drop pills involved in the present invention is compared with Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae, has following beneficial effect:
1. tendril-leaved fritillary bulb loquat drop pills involved in the present invention; utilize surfactant to be substrate; make solid dispersion with extractum that contains active constituents of medicine or dry powder; making medicine be molecule, colloid or microcrystalline state is scattered in the substrate; the total surface area of medicine increases, and substrate is hydrophilic, and medicine is had wetting action; can make that medicine is rapidly molten to loose into microgranule or solution, thereby make the dissolving of medicine and absorb and accelerate.Thereby improved bioavailability, brought into play efficient, quick-acting effects etc.
Compare with the administering mode of traditional oral formulations, exist essential distinction.Drop pill with the solid dispersion technology preparation can adopt oral and sublingual administration, and effective ingredient is fully contacted with mucomembranous surface, absorbs by mucomembranous epithelial cell, directly enters blood circulation.Owing to directly enter blood circulation without gastrointestinal tract and liver, avoided first pass effect effectively, also avoided gastrointestinal irritation, thereby it is rapid to have an onset, bioavailability height, characteristics such as side effect is little, and medication is convenient.
2. tendril-leaved fritillary bulb loquat drop pills 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. tendril-leaved fritillary bulb loquat drop pills 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 tendril-leaved fritillary bulb loquat drop pills 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 tendril-leaved fritillary bulb loquat drop pills of the present invention.
First group: the test of single-matrix
1. the ratio that provides according to [preparation method] 1 takes by weighing the raw material of Chinese medicine of some, and it is standby to save the extract dry powder that makes four kinds of pure active ingredient of Chinese herbs such as containing Bulbus Fritillariae Cirrhosae fluidextract, Radix Platycodonis, Folium Eriobotryae, Mentholum earlier according to [appendix: a kind of preparation method of Chinese medicine extract] again;
2. substrate: Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), pharmaceutically suitable carrier such as polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac;
3. proportioning---with g or kg is unit, by weight, and drug extract: substrate=1: 1～1: 9;
4. be prepared according to the process of [preparation method] 4～7 again, promptly can make the tendril-leaved fritillary bulb cough-relieving drop pills of various different sizes.
[result of the test]
Test 1: for observe drug extract and different substrates when 1: 1 the proportioning prepared tendril-leaved fritillary bulb loquat drop pills 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 tendril-leaved fritillary bulb loquat drop pills 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 tendril-leaved fritillary bulb loquat drop pills 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. the ratio that provides according to [preparation method] 1 takes by weighing the raw material of Chinese medicine of some, and it is standby to save the extract dry powder that makes four kinds of pure active ingredient of Chinese herbs such as containing Bulbus Fritillariae Cirrhosae fluidextract, Radix Platycodonis, Folium Eriobotryae, Mentholum earlier according to [appendix: a kind of preparation method of Chinese medicine extract] again;
2. substrate:
2.1 Polyethylene Glycol---English name Maerogol,
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.
[result of the test]
Test 4: for observe drug extract and mixed-matrix when 1: 1 the proportioning prepared tendril-leaved fritillary bulb loquat drop pills 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 tendril-leaved fritillary bulb loquat drop pills 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 tendril-leaved fritillary bulb loquat drop pills 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 tendril-leaved fritillary bulb loquat drop pills 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 tendril-leaved fritillary bulb loquat drop pills 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 tendril-leaved fritillary bulb loquat drop pills 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: in order to observe tendril-leaved fritillary bulb loquat drop pills that drug extract 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 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: in order to observe tendril-leaved fritillary bulb loquat drop pills that drug extract 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 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: in order to observe tendril-leaved fritillary bulb loquat drop pills that drug extract 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 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 | 63 | ＜30 | ＞10 | + |
| Polyethylene Glycol 4000 | 50.0 | 76 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 6000 | 50.0 | 79 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 8000 | 50.0 | 79 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 10000 | 50.0 | 80 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 20000 | 50.0 | 80 | ＜30 | ＞10 | ++ |
| Polyoxyethylene stearate 40 esters | 50.0 | 78 | ＜30 | ＞10 | ++ |
| Betacyclodextrin | 50.0 | 72 | ＜30 | ＞10 | + |
| Poloxamer | 50.0 | 79 | ＜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 drug extract and single-matrix
(drug extract: substrate=1: 3)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyethylene Glycol 2000 | 25.0 | 79 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 4000 | 25.0 | 86 | ＜30 | ＜10 | ++ |
| Polyethylene Glycol 6000 | 25.0 | 93 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 8000 | 25.0 | 93 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 10000 | 25.0 | 92 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 20000 | 25.0 | 91 | ＜30 | ＜10 | ++ |
| Polyoxyethylene stearate 40 esters | 25.0 | 92 | ＜30 | ＜10 | ++ |
| Betacyclodextrin | 25.0 | 82 | ＜30 | ＞10 | ++ |
| Poloxamer | 25.0 | 89 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium | 25.0 | 80 | ＜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 drug extract and single-matrix
(drug extract: substrate=1: 9)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyethylene Glycol 2000 | 10.0 | 83 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 4000 | 10.0 | 93 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 6 000 | 10.0 | 94 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 8000 | 10.0 | 92 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 10000 | 10.0 | 93 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 20000 | 10.0 | 92 | ＜30 | ＜10 | +++ |
| Polyoxyethylene stearate 40 esters | 10.0 | 93 | ＜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 drug extract and mixed-matrix
(drug extract: mixed-matrix=1: 1)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 1 | 50 | 85 | ＜30 | ＜10 | ++ |
| Poloxamer: Polyethylene Glycol=1: 1 | 50 | 86 | ＜30 | ＜10 | ++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | 50 | 81 | ＜30 | ＞10 | ++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | 50 | 78 | ＜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 | 92 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 1 | 25 | 93 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | 25 | 89 | ＜30 | ＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | 25 | 86 | ＜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 | 92 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 1 | 10 | 92 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | 10 | 90 | ＜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 | 94 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 5 | 50 | 94 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 5 | 50 | 89 | ＜30 | ＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | 50 | 83 | ＜30 | ＞10 | ++ |
The group practices of table 8 drug extract and mixed-matrix
(drug extract: mixed-matrix=1: 3)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 5 | 25 | 94 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 5 | 25 | 95 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 5 | 25 | 92 | ＜30 | ＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | 25 | 89 | ＜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 | 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 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 | 89 | ＜30 | ＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 10 | 50 | 82 | ＜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 | 94 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 10 | 25 | 93 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 10 | 25 | 90 | ＜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 | 94 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 10 | 10 | 93 | ＜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 drug extract and substrate was 1: 1, its rounding rate, the ball method of double differences was different and index such as hardness is all undesirable, and dissolve scattered time limit influenced not obvious.
2. when the ratio of drug extract and substrate is 1: 3, the rounding rate, the ball method of double differences is different and index such as hardness slightly all begins to enter preferable state.
3. when the ratio of drug extract and substrate is 1: 9, though the rounding rate, the ball method of double differences is different and index such as hardness has raising, and is not obvious.
4. the general effect of composite interstitial substance is better than single-matrix.
5. the hardness method for expressing in the subordinate list adopts drop pill is placed on the glass plate, press...withes one's finger it, observes its metamorphosis."+" expression flicking promptly is out of shape, " ++ " expression distortion of firmly pressing, and " +++" expression is indeformable by it.
Claims (2)
1. tendril-leaved fritillary bulb loquat drop pills for the treatment of cough and diseases such as chronic bronchitis, with Bulbus Fritillariae Cirrhosae fluidextract, Radix Platycodonis, Folium Eriobotryae, Mentholum is raw material, obtain containing the extract thick paste of these four kinds of active ingredient of Chinese herbs through extraction, be prepared from a certain proportion of pharmaceutically suitable carrier again, wherein:
(1) gets the some coarse powder that are ground into of Bulbus Fritillariae Cirrhosae,, make solvent with 70% ethanol according to percolation under Chinese Pharmacopoeia version appendix IO fluid extract in 2000 and the extractum item, flood after 5 days, slowly percolation is collected the liquid of just filtering, device is preserved in addition, continue percolation, the soluble component of waiting is filtered out fully, gets the liquid of filtering and is concentrated in right amount, add the liquid of just filtering, mix, continue to be concentrated into relative density under 60 ℃ and be 1.1～1.2 thick paste, standby;
According to the weight of above-mentioned Bulbus Fritillariae Cirrhosae extractum, get the Radix Platycodonis of equivalent, 6.67 times Folium Eriobotryae, Radix Platycodonis, loquat leaf are decocted with water secondary, 2.5 hours for the first time, 2 hours for the second time, collecting decoction filters, and it is 1.3～1.4 that 60 ℃ of following filtrates are concentrated into relative density, add above-mentioned Bulbus Fritillariae Cirrhosae extractum, put coldly, add and to be no more than 1% Mentholum, stir and make evenly, promptly get the extract that contains pharmaceutically active ingredient in above-mentioned four flavors, standby;
(2) described carrier is the mixture of Polyethylene Glycol and polyoxyethylene stearate 40 esters or poloxamer, and the weight ratio of polyoxyethylene stearate 40 esters or poloxamer and Polyethylene Glycol is 5: 1, and the ratio of described extract and described carrier is 1: 3;
(3) according to aforementioned proportion, accurately take by weighing described extract and substrate, place in the heating container heating while stirring, standby until the fused solution that obtains containing described drug extract and described carrier and/or emulsion and/or suspension;
(4) 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 40 ℃～-5 ℃;
When (5) treating that dropping-pill machine head and condensing agent are stable respectively and reach described state of temperature, the Mentholum adding is contained in the fused solution and/or emulsion and/or suspension of described extract and carrier, under the temperature conditions close with the water dropper temperature, make evenly through fully stirring, insulation, place in the water dropper jar of drop pill machine, splash in the condensing agent by water dropper and shrink shaping promptly.
2. tendril-leaved fritillary bulb loquat drop pills as claimed in claim 1 is characterized in that: described condensing agent be methyl-silicone oil or/and liquid paraffin or/and vegetable oil.
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| CN103083528A (en) * | 2011-11-08 | 2013-05-08 | 天津中新药业集团股份有限公司第六中药厂 | Tendril-leaved fritillary bulb loquat dropping pill for treating cough and preparation method |
| CN103041139A (en) * | 2012-09-07 | 2013-04-17 | 孙瑞龙 | Internal Chinese medicament for treating wind-heat affecting lung type chronic bronchitis |
| CN110090262A (en) * | 2018-01-30 | 2019-08-06 | 北京盈科瑞创新药物研究有限公司 | A kind of Compound Loquat cough-relieving sucking pharmaceutical solutions and preparation method thereof |
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| CN1362181A (en) * | 2001-01-02 | 2002-08-07 | 杨孟君 | Nano fritillary-loquat medicine and its preparation |
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| Title |
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| 中华人民共和国药典2000年版一部. 药典委员会，363，化学工业出版社. 2000 * |
| 中药药剂学. 范碧亭，380，381，上海科学技术出版社. 1997 * |
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Owner name: BEIJING ZHENGDA LVZHOU PHARMACY CO., LTD. Free format text: FORMER OWNER: ZHENGDA-LUZHOU MEDICINE SCIENCE-TECHNOLOGY CO., LTD., BEIJING Effective date: 20080509 |
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