CN1634511A - Fengshining drop pill for treating rheumatism and its preparation method - Google Patents
Fengshining drop pill for treating rheumatism and its preparation method Download PDFInfo
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Abstract
The invention discloses a medicinal composition, i.e. a compound drop pill for treating rheumatism, which has the functions of dispersing pathogenic wind and dehumidifying, promoting blood circulation, relieving pain, and can be applied for the treatment of rheumatalgia and joint pains. The medicine is prepared through the conventional drop pill preparing process and has the advantages of high biological availability, quick-speed medicine release, quick-speed effect, less toxic and side effects, higher medicinal content, smaller amount of administration, accurate administration dosage, easy administration, low price, and facilitated carrying.
Description
Technical field
The present invention relates to a kind of expelling wind and removing dampness that has, the promoting blood circulation and stopping pain effect is used for the treatment of rheumatalgia, and the pharmaceutical composition of arthralgia particularly based on the prescription of Chinese traditional patent formulation compound recipe anti-rheumatism injection, is changed a social system a kind of oral formulations that forms through dosage form.
Background technology
The compound recipe anti-rheumatism injection that is prepared from according to the prescription that provides among the drug standard WS-11334 (ZD-1334)-2002 and extraction process, be a kind of rheumatalgia that is used for the treatment of, the Chinese medicine of arthralgia, through clinical verification for many years, steady quality, determined curative effect is the common drug that is used for the treatment of above-mentioned disease clinically.
Below be prescription and the extraction process that provides among the drug standard WS-11334 (ZD-1334)-2002:
Prescription: Radix Zanthoxyli 2500g, Radix Schefflerae Arboricolae (Caulis et Folium Schefflerae Arboricolae) 2500g, Herba Lycopodii 1667g, Caulis Bauhihiae Championii 1667g, Radix Clematidis 833g, Radix Crotonis Crassifolii 833g, active carbon 1.5g;
Method for making: above Six-element medical material, decoct with water secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction, filter, filtrate is concentrated into the clear paste that relative density is 1.25～1.30 (40 ℃), adds ethanol and makes and contain the alcohol amount and reach 75%, left standstill 24 hours, filter, filtrate recycling ethanol also is concentrated into the clear paste that relative density is 1.25～1.30 (40 ℃), the same again method precipitate with ethanol of qinghuo reagent, concentrates once.Clear paste after concentrating is put to outdoor temperature, and adding water to relative density is 1.02 (25 ℃), and the neutral lead acetate of adding amount of liquid medicine 1% stirs, and leaves standstill 24 hours, filters, and gets filtrate and adds 10% sulfuric acid solution to there not being the precipitation generation, leaves standstill 24 hours, filters.Filtrate adds 10% sodium hydroxide solution makes neutrality, filters, and filtrate is concentrated into the clear paste that relative density is 1.25～1.30 (40 ℃).Qinghuo reagent adds ethanol and makes and contain alcohol amount to 80%, leaves standstill 24 hours, get supernatant and reclaim ethanol and be concentrated into the thick paste that relative density is 1.29～1.31 (40 ℃), add the water for injection dilution of 10 times of amounts, cold preservation 12 hours, filter, filtrate adds the injection water to an amount of, regulates PH to neutral with 10% sodium hydroxide solution, add the injection water again to ormal weight, add active carbon, boil, filter, embedding, sterilization, promptly.
Be explained as follows for this product in the appended compound recipe anti-rheumatism injection description:
Nomenclature of drug: compound recipe anti-rheumatism injection;
Main component: Radix Zanthoxyli, Radix Schefflerae Arboricolae (Caulis et Folium Schefflerae Arboricolae), Herba Lycopodii, Caulis Bauhihiae Championii, Radix Clematidis, Radix Crotonis Crassifolii;
Character: this product is brown xanchromatic clear liquid;
Function cures mainly: expelling wind and removing dampness, promoting blood circulation and stopping pain.Be used for rheumatalgia, arthralgia;
Usage and dosage: intramuscular injection, a 2-4ml, 1-2 time on the one;
Writing out a prescription with this is that the oral formulations that make on the basis has tablet, capsule.
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.Owing to be subjected to the influence of existing injection technology of preparing restriction and Chinese medicinal ingredients complexity, Chinese medicine injection often is easy to generate acute allergic reaction or untoward reaction, it is big also to exist operation easier simultaneously, the patient suffering is big, make and the medical treatment cost height, transportation stores inconvenience, and patient economy burden is heavy, shortcomings such as unsuitable family use.Therefore, be necessary to seek the peroral dosage form of better Flos Carthami medicine to satisfy the needs that clinical treatment and family use.
In addition, conventional peroral dosage form as tablet, capsule etc., because the technology of granulation is arranged, therefore can produce bigger dust pollution in preparation process, can staff's health be worked the mischief to a certain extent, also can cause certain pollution to environment simultaneously.Moreover, the complex manufacturing of conventional oral formulations, production cost is higher, thereby patient's drug cost is also improved thereupon, is unfavorable for improving the ability of seeking medical advice of extensive patients, also is unfavorable for improving the general health level of society.
Summary of the invention
Purpose of the present invention is that additional having now is used for the treatment of rheumatalgia, and the deficiency of the oral drug preparation of diseases such as arthralgia provides a kind of bioavailability height, release fast, quick produce effects, toxic and side effects is little, manufacturing and medical treatment cost are low, low price, the dropping pill formulation that is suitable for family to use.
Dropping pill formulation involved in the present invention determines that through a large amount of experiment sievings based on Chinese traditional patent formulation compound recipe anti-rheumatism injection extracting process, 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 compound recipe Fengshining drop pill involved in the present invention:
[preparation method]
1. be unit with g or kg, calculate, get 3 parts of Radix Zanthoxylis, 3 parts of Radix Schefflerae Arboricolae (Caulis et Folium Schefflerae Arboricolae)s, 2 parts of Herba Lycopodii, 2 parts of Caulis Bauhihiae Championiis, 1 part of Radix Clematidis, 1 part of Radix Crotonis Crassifolii according to weight, through the extracting method of routine 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, fused solution and/or the emulsion and/or the suspension that will contain drug extract and substrate, under the temperature conditions close, make evenly through fully stirring with the water dropper temperature, under the state of 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: a kind of preparation method of Chinese medicine extract]
With g or kg is unit, takes by weighing 3 parts of Radix Zanthoxylis, 3 parts of Radix Schefflerae Arboricolae (Caulis et Folium Schefflerae Arboricolae)s, 2 parts of Herba Lycopodii, 2 parts of Caulis Bauhihiae Championiis, 1 part of Radix Clematidis, 1 part of Radix Crotonis Crassifolii according to weight.Above Six-element medical material, decoct with water secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction, filter, filtrate is concentrated into the clear paste that relative density is 1.25～1.30 (40 ℃), adds ethanol and makes and contain the alcohol amount and reach 75%, left standstill 24 hours, filter, filtrate recycling ethanol also is concentrated into the clear paste that relative density is 1.25～1.30 (40 ℃), the same again method precipitate with ethanol of qinghuo reagent, concentrates once.Clear paste after concentrating is put to outdoor temperature, and adding water to relative density is 1.02 (25 ℃), and the neutral lead acetate of adding amount of liquid medicine 1% stirs, and leaves standstill 24 hours, filters, and gets filtrate and adds 10% sulfuric acid solution to there not being the precipitation generation, leaves standstill 24 hours, filters.Filtrate adds 10% sodium hydroxide solution makes neutrality, filters, and filtrate is concentrated into the clear paste that relative density is 1.25～1.30 (40 ℃).Qinghuo reagent adds ethanol and makes and contain alcohol amount to 80%, leaves standstill 24 hours, get supernatant and reclaim ethanol and be concentrated into the thick paste that relative density is 1.29～1.31 (40 ℃), or with thick paste at 0.1Mpa, drying and crushing under 60 ℃ the condition promptly gets dry powder;
Given here is according to a kind of preparation method of extract comparatively commonly used, its processing step adjustment is formed again.Similarly method is a lot, is not limited to this a kind of method during actual enforcement.
Beneficial effect
The compound recipe anti-rheumatism injection that is prepared from according to the prescription that provides among the drug standard WS-11334 (ZD-1334)-2002 and extraction process, be a kind of rheumatalgia that is used for the treatment of, the pure Chinese medicine of arthralgia, through clinical verification for many years, steady quality, determined curative effect is the common drug that is used for the treatment of above-mentioned disease clinically.This product also has dosage forms such as tablet, capsule at present.
Owing to reasons such as technologies of preparing, the oral formulations of most drug, especially the oral formulations of Chinese medicine, exist all after taking that dissolve scattered time limit is long, dissolution is low, absorption is relatively poor, problem such as liver sausage first pass effect and bioavailability are lower, thereby influence the performance of drug effect, also directly affect therapeutic effect.
In addition, conventional peroral dosage form as tablet, capsule etc., because the technology of granulation is arranged, therefore can produce bigger dust pollution in preparation process, can staff's health be worked the mischief to a certain extent, also can cause certain pollution to environment simultaneously.Moreover, the complex manufacturing of conventional oral formulations, production cost is higher, thereby patient's drug cost is also improved thereupon, is unfavorable for improving the ability of seeking medical advice of extensive patients, also is unfavorable for improving the general health level of society.
Compound recipe Fengshining drop pill involved in the present invention and compound recipe anti-rheumatism injection and tablet, capsule are compared, and following beneficial effect is arranged:
1. compound recipe Fengshining drop pill involved in the present invention; utilize surfactant to be substrate; make solid dispersion with the thick paste or the dry powder that contain active constituents of medicine such as Radix Zanthoxyli, Radix Schefflerae Arboricolae (Caulis et Folium Schefflerae Arboricolae), Herba Lycopodii, Caulis Bauhihiae Championii, Radix Clematidis, Radix Crotonis Crassifolii; making medicine be molecule, colloid or microcrystalline state is scattered in the substrate; the total surface area of medicine increases; and substrate is hydrophilic; medicine 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.
Chinese patent medicine injection series products is because of producing and basic research seriously lags behind, and the standardization issue of medicine never is resolved.The Chinese crude drug raw material itself is exactly a miscellaneous complex of chemical constituent, also there is not a kind of effective quality control method can reflect the quality and the difference thereof of product comprehensively, comprehensively, truly so far, and can carry out the quality control of production overall process effectively, cause the drug quality instability.The untoward reaction of Chinese medicine at present happens occasionally, but can't fundamentally understand fully to be due to which kind of composition, therefore can not in time make and deal with the aftermath of remedial measure targetedly, stay hidden danger for the hospital clinical medication.Injection manufacturing in addition, cost of transportation height use inconvenience, and this had both increased the weight of patient economy burden, have increased the misery of using again.Compare with Flos Carthami injection, the oral administration dripping pill agent has avoided medicine directly into blood, can reduce acute toxic and side effects and anaphylactoid generation effectively, and is safe and convenient to use, and effect is lasting, applied range; Manufacturing and medical treatment cost reduce greatly simultaneously, have effectively alleviated patient's financial burden, and have stored, transport, carry and use all more convenient.
2. compound recipe Fengshining drop pill involved in the present invention contacts promptly with saliva and to dissolve rapidly, and is absorbed by oral mucosa, and is not only rapid-action, and the influence of not taken food, and promptly all can containing take after meal ante cibum.
3. compound recipe Fengshining drop pill involved in the present invention mixes the extract that contains active constituents of medicine mutually with molten matrix, splashes in the not miscible condensed fluid and makes.Therefore, the stability of drug height, not facile hydrolysis, oxidation, and the operation be under liquid state, to carry out, no dust pollution is not subject to the influence of crystal formation, thereby has guaranteed the quality of medicine, has increased stability.
In sum, make compound recipe Fengshining drop pill involved in the present invention have the advantage of triple effect (quick-acting, efficient, long-acting), three little (taking dose is little, toxicity is little, side effect little), five convenience (convenient for production, store convenience, convenient transportation, easy to carry, easy to use), meet the basic demand of modernization of Chinese medicine theory.
The specific embodiment
Now with several groups of specific embodiments, be described further with regard to the preparation method of compound recipe Fengshining drop pill 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 make the extract dry powder that contains Chinese medicine Radix Zanthoxyli, Radix Schefflerae Arboricolae (Caulis et Folium Schefflerae Arboricolae), Herba Lycopodii, Caulis Bauhihiae Championii, Radix Clematidis, Radix Crotonis Crassifolii isoreactivity composition earlier according to [appendix: a kind of preparation method of Chinese medicine extract] joint 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 compound recipe Fengshining drop pill of various different sizes.
[result of the test]
Test 1: for observe drug extract and different substrates when 1: 1 the proportioning prepared compound recipe Fengshining drop pill in qualitative difference, according to 1: 1 ratio, with drug extract respectively with Polyethylene Glycol
2000, Polyethylene Glycol
4000, Polyethylene Glycol
6000, Polyethylene Glycol
8000, Polyethylene Glycol
10000, Polyethylene Glycol
20000, pharmaceutically suitable carrier such as polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac matches, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain 15 pharmaceutical compositions experiments that contain drug extract and different substrates, and obtain 15 groups of different experimental results and see Table 1.
Test 2: for observe drug extract and different substrates when 1: 3 the proportioning prepared compound recipe Fengshining drop pill in qualitative difference, according to 1: 3 ratio, with drug extract respectively with Polyethylene Glycol
2000, Polyethylene Glycol
4000, Polyethylene Glycol
6000, Polyethylene Glycol
8000, Polyethylene Glycol
10000, Polyethylene Glycol
20000, pharmaceutically suitable carrier such as polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac matches, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 15 pharmaceutical compositions that drug extract and different substrates constituted, 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 compound recipe Fengshining drop pill in qualitative difference, according to 1: 9 ratio, with drug extract respectively with Polyethylene Glycol
2000, Polyethylene Glycol
4000, Polyethylene Glycol
6000, Polyethylene Glycol
8000, Polyethylene Glycol
10000, Polyethylene Glycol
20000, pharmaceutically suitable carrier such as polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac matches, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 15 pharmaceutical compositions that drug extract and different substrates constituted, 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 active constituents of medicine such as containing Chinese medicine Radix Zanthoxyli, Radix Schefflerae Arboricolae (Caulis et Folium Schefflerae Arboricolae), Herba Lycopodii, Caulis Bauhihiae Championii, Radix Clematidis, Radix Crotonis Crassifolii earlier according to [appendix: a kind of preparation method of Chinese medicine extract] again;
2. substrate:
2.1 Polyethylene Glycol---English name Macrogol,
2.2 polyoxyethylene stearate 40 esters---English name Polyoxyl (40) Stearate,
Molecular formula is with C
17H
35COO (CH
2CH
2O)
nH represents that n is about 40,
2.3 poloxamer---English name Poloxamer, polyoxyethylene poly-oxygen propylene aether,
Molecular formula HO (C
2H
4O)
a(C
3H
6O)
b(C
2H
4O)
cH,
The sodium salt of the starch carboxymethyl ester that 2.4 carboxymethyl starch sodium---English name Carboxymethylstach Sodium, starch generates with the monoxone effect under alkali condition,
2.5 betacyclodextrin---English name Betacyclodextrin, molecular formula C
6H
10O
5, this product is that ring dextrin glucosyl transferase acts on 7 glucoses that starch generates with α-1, the bonded cyclic oligosaccharide of 4-glycosidic bond;
3. (with g or kg is unit to proportioning, by weight)
3.1 the ratio of composite interstitial substance---polyoxyethylene stearate 40 esters: Polyethylene Glycol or poloxamer: Polyethylene Glycol or carboxymethyl starch sodium: Polyethylene Glycol or betacyclodextrin: Polyethylene Glycol=1: 1～1: 10,
3.2 hybrid medicine extract: mixed-matrix weight and=1: 1～1: 9,
4. be prepared according to [preparation method] again, promptly can make the compound recipe Fengshining drop pill of various different sizes.
[result of the test]
Test 4: for observe drug extract and mixed-matrix when 1: 1 the proportioning prepared compound recipe Fengshining drop pill in qualitative difference, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 1 mixed evenly as mixed-matrix, according to 1: 1 ratio drug extract is mixed mutually with 4 kinds of different mixed-matrixes again and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that drug extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 4.
Test 5: for observe drug extract and mixed-matrix when 1: 3 the proportioning prepared compound recipe Fengshining drop pill in qualitative difference, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 1 mixed evenly as mixed-matrix, according to 1: 3 ratio drug extract is mixed mutually with 4 kinds of different mixed-matrixes again and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that drug extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 5.
Test 6: for observe drug extract and mixed-matrix when 1: 9 the proportioning prepared compound recipe Fengshining drop pill in qualitative difference, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 1 mixed evenly as mixed-matrix, according to 1: 9 ratio drug extract is mixed mutually with 4 kinds of different mixed-matrixes again and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that drug extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 6.
Test 7: for observe drug extract and mixed-matrix when 1: 1 the proportioning prepared compound recipe Fengshining drop pill in qualitative difference, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 5 mixed evenly as mixed-matrix, according to 1: 1 ratio drug extract is mixed mutually with 4 kinds of different mixed-matrixes again and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that drug extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 7.
Test 8: for observe drug extract and mixed-matrix when 1: 3 the proportioning prepared compound recipe Fengshining drop pill in qualitative difference, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 5 mixed evenly as mixed-matrix, according to 1: 3 ratio drug extract is mixed mutually with 4 kinds of different mixed-matrixes again and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that drug extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 8.
Test 9: for observe drug extract and mixed-matrix when 1: 9 the proportioning prepared compound recipe Fengshining drop pill in qualitative difference, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 5 mixed evenly as mixed-matrix, according to 1: 9 ratio drug extract is mixed mutually with 4 kinds of different mixed-matrixes again and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that drug extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 9.
Test 10: for observe drug extract and mixed-matrix when 1: 1 the proportioning prepared compound recipe Fengshining drop pill in qualitative difference, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 10 mixed evenly as mixed-matrix, according to 1: 1 ratio drug extract is mixed mutually with 4 kinds of different mixed-matrixes again and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that drug extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 10.
Test 11: for observe drug extract and mixed-matrix when 1: 3 the proportioning prepared compound recipe Fengshining drop pill in qualitative difference, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 10 mixed evenly as mixed-matrix, according to 1: 3 ratio drug extract is mixed mutually with 4 kinds of different mixed-matrixes again and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that drug extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 11.
Test 12: for observe drug extract and mixed-matrix when 1: 9 the proportioning prepared compound recipe Fengshining drop pill in qualitative difference, with polyoxyethylene stearate 40 esters, poloxamer, carboxymethyl starch sodium, 4 kinds of carriers such as betacyclodextrin respectively with Polyethylene Glycol with 1: 10 mixed evenly as mixed-matrix, according to 1: 9 ratio drug extract is mixed mutually with 4 kinds of different mixed-matrixes again and make evenly, adopt homemade drop pill machine, be prepared according to the step of stipulating in the preparation method, can obtain the experiment of 4 pharmaceutical compositions that drug extract and mixed-matrix constituted, and obtain 4 groups of different experimental results and see Table 12.
The group practices of table 1 drug extract and single-matrix
(drug extract: substrate=1: 1)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyethylene Glycol 2000 | 50.0 | 66 | ??＜30 | ??＞10 | + |
| Polyethylene Glycol 4000 | 50.0 | 72 | ??＜30 | ??＞10 | ++ |
| Polyethylene Glycol 6000 | 50.0 | 81 | ??＜30 | ??＞10 | +++ |
| Polyethylene Glycol 8000 | 50.0 | 83 | ??＜30 | ??＞10 | +++ |
| Polyethylene Glycol 10000 | 50.0 | 84 | ??＜30 | ??＜10 | +++ |
| Polyethylene Glycol 20000 | 50.0 | 86 | ??＜30 | ??＜10 | +++ |
| Polyoxyethylene stearate 40 esters | 50.0 | 75 | ??＜30 | ??＞10 | ++ |
| Betacyclodextrin | 50.0 | 74 | ??＜30 | ??＞10 | ++ |
| Poloxamer | 50.0 | 71 | ??＜30 | ??＞10 | ++ |
| Carboxymethyl starch sodium | 50.0 | 71 | ??＜30 | ??＞10 | ++ |
| Sodium lauryl sulphate | 50.0 | 69 | ??＜30 | ??＞10 | ++ |
| Stearic acid | 50.0 | 54 | ??＜30 | ??＞10 | ++ |
| Sodium stearate | 50.0 | 57 | ??＜30 | ??＞10 | +++ |
| Glycerin gelatine | 50.0 | 55 | ??＜30 | ??＞10 | +++ |
| Lac | 50.0 | 53 | ??＞30 | ??＞10 | +++ |
The group practices of table 2 drug extract and single-matrix
(drug extract: substrate=1: 3)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyethylene Glycol 2000 | ??25.0 | ??79 | ??＜30 | ??＞10 | ++ |
| Polyethylene Glycol 4000 | ??25.0 | ??82 | ??＜30 | ??＜10 | +++ |
| Polyethylene Glycol 6000 | ??25.0 | ??91 | ??＜30 | ??＜10 | +++ |
| Polyethylene Glycol 8000 | ??25.0 | ??90 | ??＜30 | ??＜10 | +++ |
| Polyethylene Glycol 10000 | ??25.0 | ??91 | ??＜30 | ??＜10 | +++ |
| Polyethylene Glycol 20000 | ??25.0 | ??92 | ??＜30 | ??＜10 | +++ |
| Polyoxyethylene stearate 40 esters | ??25.0 | ??86 | ??＜30 | ??＜10 | ++ |
| Betacyclodextrin | ??25.0 | ??84 | ??＜30 | ??＜10 | ++ |
| Poloxamer | ??25.0 | ??85 | ??＜30 | ??＜10 | +++ |
| Carboxymethyl starch sodium | ??25.0 | ??81 | ??＜30 | ??＞10 | ++ |
| Sodium lauryl sulphate | ??25.0 | ??76 | ??＜30 | ??＞10 | ++ |
| Stearic acid | ??25.0 | ??72 | ??＞30 | ??＞10 | ++ |
| Sodium stearate | ??25.0 | ??74 | ??＞30 | ??＞10 | +++ |
| Glycerin gelatine | ??25.0 | ??68 | ??＞30 | ??＞10 | +++ |
| Lac | ??25.0 | ??68 | ??＞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 | ??85 | ??＜30 | ??＞10 | ++ |
| Polyethylene Glycol 4000 | ??10.0 | ??87 | ??＜30 | ??＜10 | +++ |
| Polyethylene Glycol 6000 | ??10.0 | ??92 | ??＜30 | ??＜10 | +++ |
| Polyethylene Glycol 8000 | ??10.0 | ??91 | ??＜30 | ??＜10 | +++ |
| Polyethylene Glycol 10000 | ??10.0 | ??93 | ??＜30 | ??＜10 | +++ |
| Polyethylene Glycol 20000 | ??10.0 | ??92 | ??＜30 | ??＜10 | +++ |
| Polyoxyethylene stearate 40 esters | ??10.0 | ??89 | ??＜30 | ??＜10 | ++ |
| Betacyclodextrin | ??10.0 | ??87 | ??＜30 | ??＜10 | ++ |
| Poloxamer | ??10.0 | ??92 | ??＜30 | ??＜10 | +++ |
| Carboxymethyl starch sodium | ??10.0 | ??82 | ??＜30 | ??＞10 | +++ |
| Sodium lauryl sulphate | ??10.0 | ??81 | ??＜30 | ??＞10 | +++ |
| Stearic acid | ??10.0 | ??79 | ??＞30 | ??＞10 | +++ |
| Sodium stearate | ??10.0 | ??80 | ??＞30 | ??＞10 | +++ |
| Glycerin gelatine | ??10.0 | ??76 | ??＞30 | ??＞10 | +++ |
| Lac | ??10.0 | ??78 | ??＞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 | ??82 | ??＜30 | ??＞10 | ++ |
| Poloxamer: Polyethylene Glycol=1: 1 | ??50 | ??82 | ??＜30 | ??＞10 | ++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | ??50 | ??77 | ??＜30 | ??＞10 | ++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | ??50 | ??73 | ??＜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 | ??86 | ??＜30 | ??＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 1 | ??25 | ??88 | ??＜30 | ??＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | ??25 | ??83 | ??＜30 | ??＞10 | ++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | ??25 | ??84 | ??＜30 | ??＞10 | ++ |
The group practices of table 6 drug extract and mixed-matrix
(drug extract: mixed-matrix=1: 9)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 1 | ??10 | 87 | ??＜30 | ??＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 1 | ??10 | 86 | ??＜30 | ??＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 1 | ??10 | 84 | ??＜30 | ??＞10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 1 | ??10 | 83 | ??＜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 | 93 | ??＜30 | ??＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 5 | ??50 | 93 | ??＜30 | ??＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 5 | ??50 | 87 | ??＜30 | ??＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | ??50 | 85 | ??＜30 | ??＞10 | ++ |
The group practices of table 8 drug extract and mixed-matrix
(drug extract: mixed-matrix=1: 3)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 5 | ??25 | ??90 | ??＜30 | ??＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 5 | ??25 | ??91 | ??＜30 | ??＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 5 | ??25 | ??89 | ??＜30 | ??＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | ??25 | ??88 | ??＜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 | ??92 | ??＜30 | ??＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 5 | ??10 | ??93 | ??＜30 | ??＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 5 | ??10 | ??91 | ??＜30 | ??＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 5 | ??10 | ??90 | ??＜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 | 88 | ??＜30 | ??＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 10 | ??50 | 85 | ??＜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 | ??90 | ??＜30 | ??＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 10 | ??25 | ??92 | ??＜30 | ??＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 10 | ??25 | ??89 | ??＜30 | ??＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 10 | ??25 | ??87 | ??＜30 | ??＜10 | +++ |
The group practices of table 12 drug extract and mixed-matrix
(drug extract: mixed-matrix=1: 9)
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 10 | 10 | 93 | ??＜30 | ??＜10 | +++ |
| Poloxamer: Polyethylene Glycol=1: 10 | 10 | 92 | ??＜30 | ??＜10 | +++ |
| Carboxymethyl starch sodium: Polyethylene Glycol=1: 10 | 10 | 91 | ??＜30 | ??＜10 | +++ |
| Betacyclodextrin: Polyethylene Glycol=1: 10 | 10 | 92 | ??＜30 | ??＜10 | +++ |
1. can be seen by the result in the table: when the ratio of drug extract and substrate was 1: 1, its rounding rate, the ball method of double differences was different and index such as hardness is all undesirable, and dissolve scattered time limit influenced not obvious.
2. when the ratio of drug extract and substrate is 1: 3, the rounding rate, the ball method of double differences is different and index such as hardness slightly all begins to enter preferable state.
3. when the ratio of drug extract and substrate is 1: 9, though the rounding rate, the ball method of double differences is different and index such as hardness has raising, and is not obvious.
4. the general effect of composite interstitial substance is better than single-matrix.
5. the hardness method for expressing in the subordinate list adopts drop pill is placed on the glass plate, press...withes one's finger it, observes its metamorphosis."+" expression flicking promptly is out of shape, " ++ " expression distortion of firmly pressing, and " +++" expression is indeformable by it.
Claims (7)
1. one kind is used for the treatment of rheumatalgia, and the drug composition oral dropping pill formulation of arthralgia is a raw material with Chinese medicine Radix Zanthoxyli, Radix Schefflerae Arboricolae (Caulis et Folium Schefflerae Arboricolae), Herba Lycopodii, Caulis Bauhihiae Championii, Radix Clematidis, Radix Crotonis Crassifolii, be prepared from a certain proportion of pharmaceutically suitable carrier, wherein:
1.1. with g or kg is unit, calculates according to weight, takes by weighing 3 parts of Radix Zanthoxylis, 3 parts of Radix Schefflerae Arboricolae (Caulis et Folium Schefflerae Arboricolae)s, 2 parts of Herba Lycopodii, 2 parts of Caulis Bauhihiae Championiis, 1 part of Radix Clematidis, 1 part of Radix Crotonis Crassifolii, makes drug extract thick paste or dry powder through the extracting method of routine;
1.2. substrate---Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), one or more the mixture in pharmaceutically suitable carrier such as polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac;
1.3. proportioning---with g or kg is unit, by weight, and drug extract: substrate=1: 1～1: 9.
2. dropping pill formulation 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 dropping pill formulation as claimed in claim 1 or 2 is characterized in that: the mixed proportion of described drug extract and substrate is 1: 1～1: 5.
4. dropping pill formulation as claimed in claim 1, it is characterized in that described drug extract thick paste or dry powder obtain by the following method: with g or kg is unit, takes by weighing 3 parts of Radix Zanthoxylis, 3 parts of Radix Schefflerae Arboricolae (Caulis et Folium Schefflerae Arboricolae)s, 2 parts of Herba Lycopodii, 2 parts of Caulis Bauhihiae Championiis, 1 part of Radix Clematidis, 1 part of Radix Crotonis Crassifolii according to weight.Above Six-element medical material, decoct with water secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction, filter, filtrate is concentrated into relative density under 40 ℃ state be 1.25～1.30 clear paste, adds ethanol and make and contain the alcohol amount and reach 75%, left standstill 24 hours, filter, filtrate recycling ethanol and to be concentrated into relative density under 40 ℃ state be 1.25～1.30 clear paste, concentrates once the same again method precipitate with ethanol of qinghuo reagent.Clear paste after concentrating is put to outdoor temperature, and adding water to relative density in the time of 25 ℃ is 1.02, and the neutral lead acetate of adding amount of liquid medicine 1% stirs, and leaves standstill 24 hours, filters, and gets filtrate and adds 10% sulfuric acid solution to there not being the precipitation generation, leaves standstill 24 hours, filters.Filtrate adds 10% sodium hydroxide solution to be made neutral, filters, and filtrate is dense to be contracted under 40 ℃ state to relative density is 1.25～1.30 clear paste.Qinghuo reagent adds ethanol and makes and contain alcohol amount to 80%, leaves standstill 24 hours, and getting that supernatant reclaims ethanol and be concentrated into relative density under 40 ℃ state is 1.29～1.31 thick paste, or with thick paste at 0.1Mpa, drying and crushing under 60 ℃ the condition promptly gets dry powder.
5. the preparation method of a dropping pill formulation is characterized in that being made of following process:
5.1. with g or kg is unit, calculates according to weight, takes by weighing 3 parts of Radix Zanthoxylis, 3 parts of Radix Schefflerae Arboricolae (Caulis et Folium Schefflerae Arboricolae)s, 2 parts of Herba Lycopodii, 2 parts of Caulis Bauhihiae Championiis, 1 part of Radix Clematidis, 1 part of Radix Crotonis Crassifolii, through the extracting method of routine make the drug extract thick paste or dry powder standby;
5.2. substrate---Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), one or more the mixture in pharmaceutically suitable carrier such as polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac;
5.3. proportioning---with g or kg is unit, by weight, and drug extract: substrate=1: 1～1: 9;
5.4., accurately take by weighing drug extract and substrate according to the given ratio of prescription, be placed on heating while stirring in the heating container, standby until the fused solution that obtains containing drug extract and substrate and/or emulsion and/or suspension;
5.5. adopt homemade or general drop pill machine, and adjust the temperature control system of drop pill machine, make the water dropper temperature heating of drop pill machine and remain on 50 ℃～90 ℃, the temperature cooling of condensing agent also remains on-5 ℃～40 ℃;
5.6. treating that the temperature of condensing agent in dropping-pill machine head and the condensation column is stable respectively is in above the 2nd step during desired state of temperature, fused solution and/or the emulsion and/or the suspension that will contain drug extract and substrate, under the temperature conditions close, make evenly through fully stirring with the water dropper temperature, insulation, place in the water dropper jar of drop pill machine, splash in the condensing agent by water dropper and shrink shaping promptly.
6. as the preparation method of dropping pill formulation as described in the claim 5, it is characterized in that method 5.1 described drug extract thick pastes or dry powder obtain by the following method: with g or kg is unit, takes by weighing 3 parts of Radix Zanthoxylis, 3 parts of Radix Schefflerae Arboricolae (Caulis et Folium Schefflerae Arboricolae)s, 2 parts of Herba Lycopodii, 2 parts of Caulis Bauhihiae Championiis, 1 part of Radix Clematidis, 1 part of Radix Crotonis Crassifolii according to weight.Above Six-element medical material, decoct with water secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction, filter, filtrate is concentrated into relative density under 40 ℃ state be 1.25～1.30 clear paste, adds ethanol and make and contain the alcohol amount and reach 75%, left standstill 24 hours, filter, filtrate recycling ethanol and to be concentrated into relative density under 40 ℃ state be 1.25～1.30 clear paste, concentrates once the same again method precipitate with ethanol of qinghuo reagent.Clear paste after concentrating is put to outdoor temperature, and adding water to relative density in the time of 25 ℃ is 1.02, and the neutral lead acetate of adding amount of liquid medicine 1% stirs, and leaves standstill 24 hours, filters, and gets filtrate and adds 10% sulfuric acid solution to there not being the precipitation generation, leaves standstill 24 hours, filters.Filtrate adds 10% sodium hydroxide solution to be made neutral, filters, and filtrate is dense to be contracted under 40 ℃ state to relative density is 1.25～1.30 clear paste.Qinghuo reagent adds ethanol and makes and contain alcohol amount to 80%, leaves standstill 24 hours, and getting that supernatant reclaims ethanol and be concentrated into relative density under 40 ℃ state is 1.29～1.31 thick paste, or with thick paste at 0.1Mpa, drying and crushing under 60 ℃ the condition promptly gets dry powder.
7. as the preparation method of dropping pill formulation as described in the claim 5, it is characterized in that: method 5.6 described condensing agents are methyl-silicone oils or/and liquid paraffin or/and vegetable oil.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102579606A (en) * | 2011-01-18 | 2012-07-18 | 瑞普（天津）生物药业有限公司 | Anticoccidial traditional Chinese medicine preparation and preparation method thereof |
| CN102920828A (en) * | 2012-11-22 | 2013-02-13 | 金秀瑶族自治县瑶医医院 | External adhesive plaster for treating rheumatism and ostalgia and preparation method of external adhesive plaster |
| CN110507740A (en) * | 2019-09-04 | 2019-11-29 | 钟宇 | A kind of traditional Chinese medicine preparation for treating rheumatoid arthritis and its preparation method and application |
-
2004
- 2004-12-13 CN CNB2004100971613A patent/CN100364505C/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102579606A (en) * | 2011-01-18 | 2012-07-18 | 瑞普（天津）生物药业有限公司 | Anticoccidial traditional Chinese medicine preparation and preparation method thereof |
| CN102579606B (en) * | 2011-01-18 | 2015-03-11 | 瑞普（天津）生物药业有限公司 | Anticoccidial traditional Chinese medicine preparation and preparation method thereof |
| CN102920828A (en) * | 2012-11-22 | 2013-02-13 | 金秀瑶族自治县瑶医医院 | External adhesive plaster for treating rheumatism and ostalgia and preparation method of external adhesive plaster |
| CN102920828B (en) * | 2012-11-22 | 2014-05-28 | 金秀瑶族自治县瑶医医院 | External adhesive plaster for treating rheumatism and ostalgia and preparation method of external adhesive plaster |
| CN110507740A (en) * | 2019-09-04 | 2019-11-29 | 钟宇 | A kind of traditional Chinese medicine preparation for treating rheumatoid arthritis and its preparation method and application |
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