CN1307977C - Propolis dripping pills for treating toothache and its preparation method - Google Patents
Propolis dripping pills for treating toothache and its preparation method Download PDFInfo
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- CN1307977C CN1307977C CNB2004100967092A CN200410096709A CN1307977C CN 1307977 C CN1307977 C CN 1307977C CN B2004100967092 A CNB2004100967092 A CN B2004100967092A CN 200410096709 A CN200410096709 A CN 200410096709A CN 1307977 C CN1307977 C CN 1307977C
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- metronidazole
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- 241000241413 Propolis Species 0.000 title claims abstract description 60
- 229940069949 propolis Drugs 0.000 title claims abstract description 60
- 208000004371 toothache Diseases 0.000 title claims abstract description 44
- 238000002360 preparation method Methods 0.000 title claims abstract description 40
- 239000000203 mixture Substances 0.000 claims abstract description 17
- 238000000605 extraction Methods 0.000 claims abstract description 9
- 201000001245 periodontitis Diseases 0.000 claims abstract 3
- 239000000284 extract Substances 0.000 claims description 88
- 239000002202 Polyethylene glycol Substances 0.000 claims description 86
- 229920001223 polyethylene glycol Polymers 0.000 claims description 86
- 239000000758 substrate Substances 0.000 claims description 40
- -1 polyoxyethylene stearate Polymers 0.000 claims description 33
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 30
- 229920001983 poloxamer Polymers 0.000 claims description 30
- 229960000502 poloxamer Drugs 0.000 claims description 30
- 150000002148 esters Chemical class 0.000 claims description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 claims description 14
- 229960000282 metronidazole Drugs 0.000 claims description 14
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- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 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
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- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
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- 206010039587 Scarlet Fever Diseases 0.000 description 1
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- 235000001727 glucose Nutrition 0.000 description 1
- 125000002791 glucosyl group Chemical class C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 239000003292 glue Substances 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
- 210000003296 saliva Anatomy 0.000 description 1
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- FDRCDNZGSXJAFP-UHFFFAOYSA-M sodium chloroacetate Chemical compound [Na+].[O-]C(=O)CCl FDRCDNZGSXJAFP-UHFFFAOYSA-M 0.000 description 1
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Landscapes
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention discloses medical composition which has the functions of alleviating pain and stopping bleeding and is used for accessorily treating periodontitis. The aim of the present invention is to overcome the defect of the existing oral medicine preparation for treating symptoms such as periodontitis, etc. and provide a propolis dripping pill for treating toothache of the oral preparation of the medical composition. The propolis dripping pill for treating toothache has the advantages of high bioavailability, rapid medicine release, fast effects, small toxic and side effects, high medicine content, small administration dosage, accurate administration dosage, convenient administration, low cost and outgoing portability. The propolis dripping pill for treating toothache of the present invention is prepared via a preparation process for dripping pills on the basis of the extraction process for propolis tinctures for treating toothache of the Chinese medicine patent formulation.
Description
Technical field
The present invention relates to a kind of heat-clearing and toxic substances removing, the detumescence sore-throat relieving; Be used for laryngopharynx swelling and pain, single bilateral tonsillitis, the scarlet fever furuncle, the poison treatment of carbuncle furuncle and phyma etc. the pharmaceutical composition of symptom, particularly based on Chinese traditional patent formulation propolis toothache tincture, change a social system a kind of drug composition oral dropping pill formulation that forms through dosage form.
Background technology
The propolis toothache tincture that is prepared from according to the prescription that provides among the national drug standards WS-11255 (ZD-1255)-2002 and extraction process, be to have pain relieving, hemostasis, be used for periodontal disease auxiliary treatment etc. symptom tincture class preparation, 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.Also there is not other similar oral formulations at present.
Below be the prescription and the extraction process of the propolis toothache tincture that provides among the drug standard WS-11255 (ZD-1255)-2002:
Prescription: propolis 100g, Oleum Caryophylli 45ml, metronidazole 8g
Method for making: above three flavors, propolis 90% ethanol, the heating extraction secondary, each 2 hours, gradation filtered, merging filtrate, wax is removed in cold preservation 24 hours, filters, and decompression filtrate recycling ethanol gets fluid extract, adds 70% ethanol 800ml and makes dissolving, and is standby; Metronidazole is with 70% ethanol 100ml, and heating for dissolving merges with above-mentioned ethanol liquid, adds Oleum Caryophylli, stirs evenly, and adds 70% ethanol to ormal weight, stirs evenly, and leaves standstill 12 hours, filter, and fill, promptly.
Be explained as follows for this tincture in the appended propolis toothache tincture description:
Nomenclature of drug: propolis toothache tincture;
Main component: propolis, Oleum Caryophylli, metronidazole;
Character: this product is the sepia supernatant liquid; Gas fragrance, acrid in the mouth, hardship;
Function cures mainly: pain relieving, hemostasis.The auxiliary treatment that is used for periodontal disease;
Usage and dosage: this product is dripped in the affected part 1～2; Or dip in liquid with cotton swab bubble and be applied to the affected part; Or with absorbent cotton a little dips in the medicine plug in teeth space or cavity place, 2～3 times on the one.
Propolis toothache tincture belongs to liquid oral medicine, and owing to reasons such as technologies of preparing, it is low that tincture exists medicament contg, using dosage is big, and using dosage is inaccurate, uses inconvenient characteristics, also be not easy to go out to carry its storage or put easy generation precipitation for a long time, deficiencies such as its shelf-life is relatively short.
In addition, the Chinese medicine solid oral dosage form that other are conventional as tablet, capsule, granule etc., exists 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 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 pain relieving, hemostasis, is used for the deficiency of oral drug preparation of the symptoms such as auxiliary treatment of periodontal disease, provide a kind of bioavailability height, release fast, produce effects fast, toxic and side effects is littler, and the medicament contg height, taking dose is little, and taking dose is accurate, taking convenience, cheap, and be convenient to go out to carry, drug composition oral preparation propolis dripping pills for treating toothache easily stored.
Propolis dripping pills for treating toothache involved in the present invention determines that through a large amount of experiment sievings based on the extraction process of Chinese traditional patent formulation propolis toothache tincture, 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 propolis dripping pills for treating toothache involved in the present invention:
[preparation method]
1. propolis 100g makes drug extract extractum or dry powder through extraction, merges with metronidazole 8g to be mixed into the mixed extract that contains effective bee glue components and metronidazole, and is standby; Oleum Caryophylli 45ml is standby;
2. substrate---Polyethylene Glycol
(1000,2000,4000,6000,8000,9300,10000,20000), 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 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, Oleum Caryophylli 45ml 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.
[appendix: the preparation method of propolis extract]
Propolis 100g 90% ethanol, the heating extraction secondary, each 2 hours, gradation filtered, merging filtrate, wax is removed in cold preservation 24 hours, filters, and decompression filtrate recycling ethanol gets fluid extract, and is standby; Perhaps pass through low temperature, drying under reduced pressure again, pulverize, promptly get dry powder.
Given here is to change according to a kind of preparation method of extract among the drug standard WS-11255 (ZD-1255)-2002 to form, and similarly method is a lot, is not limited to this a kind of method during actual enforcement.
Beneficial effect
According to the propolis toothache tincture that the prescription that provides among the national drug standards WS-11255 (ZD-1255)-2002 and extraction process are prepared from, be pain relieving, hemostasis.The tincture class preparation that is used for the symptoms such as auxiliary treatment of periodontal disease, 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.
Propolis toothache tincture belongs to liquid oral medicine, and owing to reasons such as technologies of preparing, it is low that tincture exists medicament contg, using dosage is big, and using dosage is inaccurate, uses inconvenient characteristics, also be not easy to go out to carry its storage or put easy generation precipitation for a long time, deficiencies such as its shelf-life is relatively short.
In addition, the solid orally ingestible of most drug, especially the solid orally ingestible of Chinese medicine, as tablet, capsule etc., 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 tablet, capsule etc. in preparation process because the technology of granulation is arranged, 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.Moreover, the complex manufacturing of oral formulations such as tablet, capsule, 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.
Propolis dripping pills for treating toothache involved in the present invention is compared with propolis toothache tincture, has following beneficial effect:
1. propolis dripping pills for treating toothache involved in the present invention is compared with liquid oral medicine propolis tincture for treatment of toothache, and the solid preparation dropping pill formulation is more suitable for carrying and conveniently taking, and taking dose is accurate, and the shelf-life of drop pill is corresponding more much longer than tincture simultaneously.This is that then there is not this problem in dropping pill formulation because many medicines decompose or degraded after being processed into liquid preparation easily.
2. propolis dripping pills for treating toothache involved in the present invention; utilize surfactant etc. 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 has wetting action to medicine, 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, oral except adopting, all right sublingual administration can make effective ingredient fully contact 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.
3. propolis dripping pills for treating toothache 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, can be placed on the affected part of having a toothache, and local application's onset is faster.
4. propolis dripping pills for treating toothache 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 propolis dripping pills for treating toothache 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 propolis dripping pills for treating toothache 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, make the extract extractum that contains the pure active ingredient of Chinese herbs of propolis or dry powder and metronidazole earlier according to [appendix: the preparation method of propolis extract] one joint again and be merged into the hybrid medicine extract, standby; Oleum Caryophylli 45ml is standby;
2. substrate: Polyethylene Glycol
(1000,2000,4000,6000,8000,9300,10000,20000), 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 propolis dripping pills for treating toothache of various different sizes.
[result of the test]
Test 1: for observe drug extract and different substrates when 1: 1 the proportioning prepared propolis dripping pills for treating toothache 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 propolis dripping pills for treating toothache 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 propolis dripping pills for treating toothache 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, make the extract extractum that contains the pure active ingredient of Chinese herbs of propolis or dry powder and metronidazole earlier according to [appendix: the preparation method of propolis extract] one joint again and be merged into the hybrid medicine extract, standby; Oleum Caryophylli 45ml is standby;
2. substrate:
2.1 Polyethylene Glycol---English name Macrogol,
2.2 polyoxyethylene stearate 40 esters---English name Polyoxyl (40) Stearate,
Molecular formula is with C
17H
35COO (CH
2CH
2O)
nH represents that n is about 40,
2.3 poloxamer---English name Poloxamer, polyoxyethylene poly-oxygen propylene aether,
Molecular formula HO (C
2H
4O)
a(C
3H
6O)
b(C
2H
4O)
cH,
The sodium salt of the starch carboxymethyl ester that 2.4 carboxymethyl starch sodium---English name Carboxymethylstach Sodium, starch generates with the monoxone effect under alkali condition,
2.5 betacyclodextrin---English name Betacyclodextrin, molecular formula C
6H
10O
5, this product is that ring dextrin glucosyl transferase acts on 7 glucoses that starch generates with α-1, the bonded cyclic oligosaccharide of 4-glycosidic bond;
3. (with g or kg is unit to proportioning, by weight)
3.1 the ratio of composite interstitial substance---polyoxyethylene stearate 40 esters: Polyethylene Glycol or poloxamer: Polyethylene Glycol or carboxymethyl starch sodium: Polyethylene Glycol or betacyclodextrin: Polyethylene Glycol=1: 1～1: 10,
3.2 hybrid medicine extract: mixed-matrix weight and=1: 1～1: 9.
4. be prepared according to the process of [preparation method] 4～7 again, promptly can make the propolis dripping pills for treating toothache of various different sizes.
[result of the test]
Test 4: for observe drug extract and mixed-matrix when 1: 1 the proportioning prepared propolis dripping pills for treating toothache 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 propolis dripping pills for treating toothache 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 propolis dripping pills for treating toothache 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 propolis dripping pills for treating toothache 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 propolis dripping pills for treating toothache 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 propolis dripping pills for treating toothache 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 propolis dripping pills for treating toothache 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 propolis dripping pills for treating toothache 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 propolis dripping pills for treating toothache 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 | 77 | ＜30 | ＞10 | + |
| Polyethylene Glycol 4000 | 50.0 | 76 | ＜30 | ＞10 | +++ |
| Polyethylene Glycol 6000 | 50.0 | 90 | ＜30 | ＞10 | +++ |
| Polyethylene Glycol 8000 | 50.0 | 85 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 9300 | 50.0 | 88 | ＜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 | 81 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 4000 | 25.0 | 82 | ＜30 | ＜10 | ++ |
| Polyethylene Glycol 6000 | 25.0 | 90 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 8000 | 25.0 | 95 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 9300 | 25.0 | 87 | ＜30 | ＞10 | ++ |
| Polyethylene Glycol 10000 | 25.0 | 88 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 20000 | 25.0 | 89 | ＜30 | ＜10 | ++ |
| Polyoxyethylene stearate 40 esters | 25.0 | 78 | ＜30 | ＜10 | ++ |
| Betacyclodextrin | 25.0 | 81 | ＜30 | ＞10 | ++ |
| Poloxamer | 25.0 | 85 | ＜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 | 90 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 6000 | 10.0 | 95 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 8000 | 10.0 | 89 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 9300 | 10.0 | 85 | ＜30 | ＜10 | ++ |
| Polyethylene Glycol 10000 | 10.0 | 94 | ＜30 | ＜10 | ++ |
| Polyethylene Glycol 20000 | 10.0 | 90 | ＜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 | 75 | ＞30 | ＞10 | +++ |
| Lac | 10.0 | 70 | ＞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 | 88 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 1 | 50 | 90 | ＜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 | 95 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 1 | 25 | 90 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | 25 | 88 | ＜30 | ＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | 25 | 85 | ＜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 | 94 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 1 | 10 | 93 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | 10 | 94 | ＜30 | ＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | 10 | 88 | ＜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 | 95 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 5 | 50 | 93 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 5 | 50 | 88 | ＜30 | ＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | 50 | 82 | ＜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 | 95 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 5 | 25 | 93 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 5 | 25 | 90 | ＜30 | ＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | 25 | 87 | ＜30 | ＜10 | ++ |
The group practices of table 9 drug extract and mixed-matrix
(drug extract: mixed-matrix=1: 9)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 5 | 10 | 88 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 5 | 10 | 94 | ＜30 | ＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 5 | 10 | 90 | ＜30 | ＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | 10 | 85 | ＜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 | 94 | ＜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 | 80 | ＜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 | 95 | ＜30 | ＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 10 | 25 | 92 | ＜30 | ＜10 | ++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 10 | 25 | 88 | ＜30 | ＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 10 | 25 | 84 | ＜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 | 88 | ＜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. a propolis dripping pills for treating toothache that is used for the periodontitis auxiliary treatment is a raw material with propolis, metronidazole, Oleum Caryophylli, is prepared from the pharmaceutically suitable carrier as substrate, it is characterized in that described preparation process is as follows:
(1) propolis 100g uses 90% ethanol, the heating extraction secondary, and each 2 hours, gradation filtered, merging filtrate, wax is removed in cold preservation 24 hours, filters, and decompression filtrate recycling ethanol gets fluid extract; Perhaps pass through low temperature, drying under reduced pressure again, pulverize, it is standby promptly to get dry powder; Other gets metronidazole 8g, Oleum Caryophylli 45ml;
(2) described substrate is the mixture of Polyethylene Glycol and polyoxyethylene stearate 40 esters or poloxamer; By weight, the ratio of polyoxyethylene stearate 40 esters or poloxamer and Polyethylene Glycol is 1: 1～1: 10;
(3) weight of described propolis extract and metronidazole, Oleum Caryophylli and with the ratio of described substrate be 1: 3;
(4) according to aforementioned proportion, accurately take by weighing propolis extract, metronidazole, Oleum Caryophylli and substrate, in advance with propolis extract and metronidazole mix homogeneously, place in the heating container heating while stirring, standby until the fused solution that obtains containing propolis extract and metronidazole and substrate and/or emulsion and/or suspension;
(5) temperature control system of adjustment drop pill machine makes the water dropper temperature heating of drop pill machine and remains on 50 ℃～90 ℃, and the temperature cooling of condensing agent also remains on-5 ℃～40 ℃;
When (6) temperature for the treatment of dropping-pill machine head and condensing agent reaches above-mentioned state respectively, Oleum Caryophylli 45ml adding is contained in the fused solution and/or emulsion and/or suspension of propolis extract and metronidazole and substrate, place in the water dropper jar of drop pill machine, splash in the condensing agent and shrink shaping promptly.
2. propolis dripping pills for treating toothache according to 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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| US20070140990A1 (en) | 2005-12-21 | 2007-06-21 | Nataly Fetissova | Oral Compositions Comprising Propolis |
| CN101391098B (en) * | 2008-11-11 | 2011-05-04 | 安徽省百春制药有限公司 | Apitoxin liposome preparation and preparation method thereof |
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