CN104274737A - Method for preparing Erbao granules - Google Patents
Method for preparing Erbao granules Download PDFInfo
- Publication number
- CN104274737A CN104274737A CN201410488577.1A CN201410488577A CN104274737A CN 104274737 A CN104274737 A CN 104274737A CN 201410488577 A CN201410488577 A CN 201410488577A CN 104274737 A CN104274737 A CN 104274737A
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- parts
- bao
- preparation
- solid dispersion
- radix
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- 238000002360 preparation method Methods 0.000 claims abstract description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 22
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 15
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- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 abstract 1
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- 239000000047 product Substances 0.000 description 15
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 7
- 239000013558 reference substance Substances 0.000 description 7
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
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- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 4
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- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
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- 238000004809 thin layer chromatography Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
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- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 108010011485 Aspartame Proteins 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 2
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- 238000004519 manufacturing process Methods 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
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- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
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- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- 239000001100 (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one Substances 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
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- JWQQQOUOPSWHRU-UHFFFAOYSA-N C(=O)O.CO.C(C)(=O)O.C(Cl)(Cl)Cl Chemical compound C(=O)O.CO.C(C)(=O)O.C(Cl)(Cl)Cl JWQQQOUOPSWHRU-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/36—Caryophyllaceae (Pink family), e.g. babysbreath or soapwort
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/07—Basidiomycota, e.g. Cryptococcus
- A61K36/076—Poria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/488—Pueraria (kudzu)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/65—Paeoniaceae (Peony family), e.g. Chinese peony
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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Abstract
The invention discloses a method for preparing Erbao granules. The method comprises the following steps: grinding the following materials into coarse powder: radix pseudostellariae, radix glehniae, poria cocos, yam, roasted hawthorn, roasted malt, pericarpium citri reticulatae, stir-baked radix paeoniae alba, fried semen lablab album, radix ophiopogonis and baked kudzu vine root; decocting by water, filtering, and combining filtrates; adsorbing the filtrate by macroporous resin, eluting by an ethanol aqueous solution to obtain eluent, and concentrating the eluent to obtain a concentrated liquid; adding a solid dispersion carrier material into the concentrated liquid obtained in the step 2, stirring until the carrier material is dissolved, removing solvent, drying and grinding to obtain solid dispersion; finally, mixing the solid dispersion, a diluting agent, a flavoring agent and a wetting agent, granulating and drying to obtain the granules. The preparation process of Erbao granules is improved, so that, on the one hand, the using amount of auxiliaries is reduced, the dose for a child is reduced, and the administration compliance can be remarkably improved; on the other hand, impurities influencing storage stability of main ingredients can be effectively removed, and the stability of the granules can be improved.
Description
Technical field
The invention belongs to technical field of Chinese medicines, be specifically related to a kind of preparation method of Er'bao granule.
Background technology
The main component of Er'bao granule is Radix Pseudostellariae, Radix Glehniae, Poria, Rhizoma Dioscoreae, Fructus Crataegi (parched), Fructus Hordei Germinatus (parched), Pericarpium Citri Reticulatae, Radix Paeoniae Alba (parched), Semen Lablab Album (parched), Radix Ophiopogonis and roasted RADIX PUERARIAE.Cure mainly invigorating the spleen and benefiting QI, appetizing of promoting the production of body fluid.Weak for children's's yellowish complexion, indigestion and loss of appetite anorexia, insufficiency of the spleen chronic diarrhea, lassitude, dry mouth is thirsty, night sweat.The Er'bao granule sold in the market is every packed 15g.
With reference to Pharmacopoeia of People's Republic of China version in 2010 first, the method for making of Er'bao granule is: by Radix Pseudostellariae, Radix Glehniae, Poria, Rhizoma Dioscoreae, Fructus Crataegi (parched), Fructus Hordei Germinatus (parched), Pericarpium Citri Reticulatae, Radix Paeoniae Alba (parched), Semen Lablab Album (parched), Radix Ophiopogonis and roasted RADIX PUERARIAE ten principal agent simply, decoct with water secondary, 4 hours first times, second time 3 hours, decocting liquid filters, filtrate merges, leave standstill, get supernatant, be concentrated into appropriate; Separately get maltose 45g, heated and boiled, be concentrated into more than relative density 1.35 (50 DEG C), add citric acid 3g, stir evenly, add in above-mentioned concentrated solution, stir evenly, add cane sugar powder 650g, dextrin is appropriate, mixing, makes granule, 60 DEG C of dryings, makes 1000g; Or adding cane sugar powder 270g, dextrin in right amount, mixing, makes granule, 60 DEG C of dryings, makes 900g, to obtain final product.
The Er'bao granule obtained according to said method, supplementary product consumption is too large, causes dose large.Be child because Er'bao granule is mainly suitable for crowd, there is dose greatly and the shortcomings such as bitter in the mouth in existing Chinese medicine preparation, the poor compliance that infant is taken medicine, therefore needs to improve existing preparation.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art and the preparation method that improves a kind of Er'bao granule, gained granule decreases supplementary product consumption, and infant dose reduces, and significantly improves Compliance.
The preparation method of Er'bao granule, comprises the following steps:
Step 1, with parts by weight, get Radix Pseudostellariae 100 ~ 140 parts, Radix Glehniae 100 ~ 140 parts, 100 ~ 140 parts, Poria, Rhizoma Dioscoreae 100 ~ 140 parts, Fructus Crataegi (parched) 40 ~ 60 parts, Fructus Hordei Germinatus (parched) 40 ~ 60 parts, Pericarpium Citri Reticulatae 40 ~ 60 parts, Radix Paeoniae Alba (parched) 40 ~ 60 parts, Semen Lablab Album (parched) 100 ~ 140 parts, Radix Ophiopogonis 40 ~ 60 parts and roasted RADIX PUERARIAE 40 ~ 60 parts, be ground into powder, decoct with water, filter, merging filtrate;
Step 2, is adsorbed step 1 gained filtrate by macroporous resin, then carries out eluting with ethanol water, obtain eluent, concentrated by eluent, obtain concentrated solution;
Step 3, adds to solid dispersion carrier material in step 2 gained concentrated solution, is stirred to carrier material and dissolves, and except desolventizing also dry, pulverizing, obtains solid dispersion;
Step 4, mixes step 3 gained solid dispersion, diluent, correctives and wetting agent, and granulation, drying, to obtain final product.
As the further improvement of foregoing invention, step 1 decocts with water in process, and the weight of the water added is 2 ~ 3 times of Chinese medicinal components gross weight.
As the further improvement of foregoing invention, step 2 big pore adsorption resin is selected from AB-8, NKA, HDP-100, HDP-722 or HDP-750.
As the further improvement of foregoing invention, in step 2 ethanol water used, ethanol accounting example is 70 ~ 80wt.%.
As the further improvement of foregoing invention, step 2 gained concentrated solution 85 ~ 90 DEG C of relative densities are 1.2 ~ 1.3.
As the further improvement of foregoing invention, in step 3, the weight ratio of concentrated solution and carrier material is 1:1 ~ 10.
As the further improvement of foregoing invention, described carrier material is selected from polyvidone class, copolyvidone class, hydroxypropyl cellulose class, hypromellose class, polyethylene glycols or poloxamer class.
As the further improvement of foregoing invention, the method except desolventizing in step 3 is drying under reduced pressure.
As the further improvement of foregoing invention, in step 4, the weight ratio of solid dispersion, diluent, correctives, wetting agent is 100:10 ~ 15:4 ~ 8:0.5 ~ 1.2.
As the further improvement of foregoing invention, described diluent is starch, dextrin, maltose or lactose.
Due in digestion, the physiological pH from stomach to intestinal raises gradually.After which results in drug administration, although dissolve in the stomach, after gastric emptying enters intestinal, along with the rising of pH, the medicine of dissolving will separate out precipitation.A large amount of precipitations of medicine, make it can not remain in intestinal juice with molecularity, cannot realize cross-film and absorb, thus affect the absorption of medicine, bioavailability is reduced.Therefore, should pharmaceutics means be passed through, improve the dissolubility of medicine and drug loading, avoid its precipitation in neutral medium, thus improve the bioavailability of medicine.
At present, improve the method for insoluble drug dissolubility and dissolution, mainly contain micronization technology, inclusion technique and solid dispersions technique etc.Now there are some researches show, after drug micronization, particle diameter reduces, and surface area increases, and dissolution increases.But particle diameter is reduced to a certain degree, microgranule free energy sharply increases, and in storage process or enter after in body, have the trend of self-assemble, dissolution reduces on the contrary.And inclusion technique is owing to being subject to the restrictions such as drug molecule amount, space structure, success rate is lower, i.e. enable successful enclose, also there is the problems such as drug loading is low.
Solid dispersions technique, in raising insoluble drug dissolubility and dissolution, has more research and more significant effect.But also there is some complex process, the problems such as drug loading is low.Especially want to obtain positive effect, often need to apply a large amount of carriers, this must result in the lower drug loading of solid dispersion.For the medicine of those large usage quantities, even if after being prepared into solid dispersion, drug solubility and dissolution all significantly improve, but lower drug loading necessarily limit the dosage form being prepared into applicable clinical needs.And if solid dispersion needs to be prepared into oral solid formulation further, the dry jet mixing pile that self is poor, often also can limit it and apply further.
Solvent method prepares solid dispersion, and the method removing organic solvent generally has drying under reduced pressure, spraying dry and lyophilization.Freeze-drying is high to equipment requirements, and production cost is high, general little application.At present, drying under reduced pressure and spraying dry are most widely used.And product prepared by spray drying method often has better dissolubility, it is made to apply day by day extensive.But, the beat all discovery of the present inventor, by active component and respective carrier, with the solid dispersion that this two kinds of drying meanss are prepared into, dissolubility do not have significant difference, but the dry jet mixing pile of the solid dispersion prepared with hypobaric drying method (compressibility and mobility), is but obviously better than the product that spray drying method is obtained.
The present invention, by Chinese medicine extract and macromolecule carrier are prepared into amorphous solid dispersion by solvent method, drastically increases the drug loading of medicine.After removing organic solvent by the method for drying under reduced pressure, obtained solid dispersion, dry jet mixing pile is good, and mobility and compressibility are all better than solid dispersion prepared by prior art, can be prepared into the dosage form being convenient to clinical practice.
The present invention, by improving the preparation technology of Er'bao granule, on the one hand, decreases supplementary product consumption, and infant dose reduces, and significantly improves Compliance; On the other hand, effectively eliminate the impurity affecting main constituent storage stability, improve the stability of granule.
Detailed description of the invention
Embodiment 1
The preparation method of Er'bao granule, comprises the following steps:
Step 1, with parts by weight, get Radix Pseudostellariae 100 parts, Radix Glehniae 100 parts, 100 parts, Poria, Rhizoma Dioscoreae 100 parts, Fructus Crataegi (parched) 40 parts, Fructus Hordei Germinatus (parched) 40 parts, Pericarpium Citri Reticulatae 40 parts, Radix Paeoniae Alba (parched) 40 parts, Semen Lablab Album (parched) 100 parts, Radix Ophiopogonis 40 parts and roasted RADIX PUERARIAE 40 parts, be ground into powder, decoct with water, the weight of the water added is 2 times of Chinese medicinal components gross weight, filters, merging filtrate;
Step 2, is adsorbed step 1 gained filtrate by macroporous resin AB-8, then carries out eluting with 70wt.% ethanol water, obtain eluent, and eluent being concentrated into relative density is 1.2 (85 ~ 90 DEG C), obtains concentrated solution;
Step 3, added to by solid dispersion carrier material polyvidone in step 2 gained concentrated solution, the weight ratio of concentrated solution and carrier material is 1:1, is stirred to carrier material and dissolves, and drying under reduced pressure, except desolventizing also dry, pulverizing, obtains solid dispersion;
Step 4, step 3 gained solid dispersion, starch, mannitol and wetting agent are mixed, the weight ratio of solid dispersion, starch, mannitol, wetting agent is 100:10:4:0.5, and granulation, drying, to obtain final product.
Embodiment 2
The preparation method of Er'bao granule, comprises the following steps:
Step 1, with parts by weight, get Radix Pseudostellariae 110 parts, Radix Glehniae 110 parts, 110 parts, Poria, Rhizoma Dioscoreae 110 parts, Fructus Crataegi (parched) 45 parts, Fructus Hordei Germinatus (parched) 45 parts, Pericarpium Citri Reticulatae 45 parts, Radix Paeoniae Alba (parched) 45 parts, Semen Lablab Album (parched) 110 parts, Radix Ophiopogonis 45 parts and roasted RADIX PUERARIAE 45 parts, be ground into powder, decoct with water, the weight of the water added is 2 times of Chinese medicinal components gross weight, filters, merging filtrate;
Step 2, is adsorbed step 1 gained filtrate by macroporous resin NKA, then carries out eluting with 75wt.% ethanol water, obtain eluent, and eluent being concentrated into relative density is 1.25 (85 ~ 90 DEG C), obtains concentrated solution;
Step 3, added to by solid dispersion carrier material hydroxypropyl cellulose in step 2 gained concentrated solution, the weight ratio of concentrated solution and carrier material is 1:3, is stirred to carrier material and dissolves, and drying under reduced pressure, except desolventizing also dry, pulverizing, obtains solid dispersion;
Step 4, step 3 gained solid dispersion, dextrin, xylitol and wetting agent are mixed, the weight ratio of solid dispersion, dextrin, xylitol, wetting agent is 100:12:5:0.7, and granulation, drying, to obtain final product.
Embodiment 3
The preparation method of Er'bao granule, comprises the following steps:
Step 1, with parts by weight, get Radix Pseudostellariae 120 parts, Radix Glehniae 105 parts, 115 parts, Poria, Rhizoma Dioscoreae 125 parts, Fructus Crataegi (parched) 50 parts, Fructus Hordei Germinatus (parched) 55 parts, Pericarpium Citri Reticulatae 45 parts, Radix Paeoniae Alba (parched) 50 parts, Semen Lablab Album (parched) 125 parts, Radix Ophiopogonis 45 parts and roasted RADIX PUERARIAE 50 parts, be ground into powder, decoct with water, the weight of the water added is 3 times of Chinese medicinal components gross weight, filters, merging filtrate;
Step 2, is adsorbed step 1 gained filtrate by macroporous resin HDP-100, then carries out eluting with 80wt.% ethanol water, obtain eluent, and eluent being concentrated into relative density is 1.25 (85 ~ 90 DEG C), obtains concentrated solution;
Step 3, added to by solid dispersion carrier material Polyethylene Glycol in step 2 gained concentrated solution, the weight ratio of concentrated solution and carrier material is 1:6, is stirred to carrier material and dissolves, and drying under reduced pressure, except desolventizing also dry, pulverizing, obtains solid dispersion;
Step 4, step 3 gained solid dispersion, maltose, steviosin and wetting agent are mixed, the weight ratio of solid dispersion, maltose, steviosin, wetting agent is 100:13:7:0.9, and granulation, drying, to obtain final product.
Embodiment 4
The preparation method of Er'bao granule, comprises the following steps:
Step 1, with parts by weight, get Radix Pseudostellariae 135 parts, Radix Glehniae 130 parts, 125 parts, Poria, Rhizoma Dioscoreae 110 parts, Fructus Crataegi (parched) 45 parts, Fructus Hordei Germinatus (parched) 50 parts, Pericarpium Citri Reticulatae 55 parts, Radix Paeoniae Alba (parched) 50 parts, Semen Lablab Album (parched) 120 parts, Radix Ophiopogonis 50 parts and roasted RADIX PUERARIAE 45 parts, be ground into powder, decoct with water, the weight of the water added is 3 times of Chinese medicinal components gross weight, filters, merging filtrate;
Step 2, is adsorbed step 1 gained filtrate by macroporous resin HDP-722, then carries out eluting with 70wt.% ethanol water, obtain eluent, and eluent being concentrated into relative density is 1.25 (85 ~ 90 DEG C), obtains concentrated solution;
Step 3, added to by solid dispersion carrier material poloxamer in step 2 gained concentrated solution, the weight ratio of concentrated solution and carrier material is 1:7, is stirred to carrier material and dissolves, and drying under reduced pressure, except desolventizing also dry, pulverizing, obtains solid dispersion;
Step 4, step 3 gained solid dispersion, lactose, aspartame and wetting agent are mixed, the weight ratio of solid dispersion, lactose, aspartame, wetting agent is 100:14:7:0.9, and granulation, drying, to obtain final product.
Embodiment 5
The preparation method of Er'bao granule, comprises the following steps:
Step 1, with parts by weight, get Radix Pseudostellariae 140 parts, Radix Glehniae 140 parts, 140 parts, Poria, Rhizoma Dioscoreae 140 parts, Fructus Crataegi (parched) 60 parts, Fructus Hordei Germinatus (parched) 60 parts, Pericarpium Citri Reticulatae 60 parts, Radix Paeoniae Alba (parched) 60 parts, Semen Lablab Album (parched) 140 parts, Radix Ophiopogonis 60 parts and roasted RADIX PUERARIAE 60 parts, be ground into powder, decoct with water, the weight of the water added is 3 times of Chinese medicinal components gross weight, filters, merging filtrate;
Step 2, is adsorbed step 1 gained filtrate by macroporous resin HDP-750, then carries out eluting with 80wt.% ethanol water, obtain eluent, and eluent being concentrated into relative density is 1.25 (85 ~ 90 DEG C), obtains concentrated solution;
Step 3, solid dispersion carrier material copolyvidone added in step 2 gained concentrated solution, the weight ratio of concentrated solution and carrier material is 1:10, is stirred to carrier material and dissolves, and drying under reduced pressure, except desolventizing also dry, pulverizing, obtains solid dispersion;
Step 4, step 3 gained solid dispersion, maltose, steviosin and wetting agent are mixed, the weight ratio of solid dispersion, maltose, steviosin, wetting agent is 100:15:8:1.2, and granulation, drying, to obtain final product.
Comparative example 1
With reference to Pharmacopoeia of People's Republic of China version in 2010 first, the method for making of Er'bao granule is: by Radix Pseudostellariae, Radix Glehniae, Poria, Rhizoma Dioscoreae, Fructus Crataegi (parched), Fructus Hordei Germinatus (parched), Pericarpium Citri Reticulatae, Radix Paeoniae Alba (parched), Semen Lablab Album (parched), Radix Ophiopogonis and roasted RADIX PUERARIAE ten principal agent simply, decoct with water secondary, 4 hours first times, second time 3 hours, decocting liquid filters, filtrate merges, leave standstill, get supernatant, be concentrated into appropriate; Separately get maltose 45g, heated and boiled, be concentrated into more than relative density 1.35 (50 DEG C), add citric acid 3g, stir evenly, add in above-mentioned concentrated solution, stir evenly, add cane sugar powder 650g, dextrin is appropriate, mixing, makes granule, 60 DEG C of dryings, makes 1000g; Or adding cane sugar powder 270g, dextrin in right amount, mixing, makes granule, 60 DEG C of dryings, makes 900g, to obtain final product.
Experimental example
With reference to Pharmacopoeia of People's Republic of China version first in 2010, above-described embodiment sample is tested.
[character] this product is the faint yellow granule to brown color; Sweet, the micro-acid of taste.
This product 50g is got, porphyrize in [discriminating] (1), and add diethyl ether 80mL, reflux 1 hour, and filter, filtrate evaporate to dryness, residue adds methanol 0.5mL makes dissolving, as need testing solution.Separately get Radix Pseudostellariae control medicinal material 3g, add water 50mL, decocts 1 hour, centrifugal, gets supernatant, extract 2 times with ether jolting, each 40mL, and merge ether solution, evaporate to dryness, residue adds methanol 0.5mL makes dissolving, medical material solution in contrast.According to thin layer chromatography test, draw each 20 μ L of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with cyclohexane-ethyl acetate (9:1) for developing solvent, launch, take out, dry, spray with 5% vanillin-sulfuric acid solution, be heated to spot development at 105 DEG C clear.In test sample chromatograph, on the position corresponding to control medicinal material chromatograph, the speckle of aobvious same color.
(2) get this product 10g, porphyrize, add ethyl acetate 30mL, reflux 1 hour, filter, filtrate evaporate to dryness, residue adds methanol 1mL makes dissolving, as need testing solution.Separately get Hesperidin reference substance, add methanol and make saturated solution, in contrast product solution.Test according to thin layer chromatography, draw need testing solution 5 ~ 10 μ L, reference substance solution 5 μ L, put on the silica gel g thin-layer plate prepared in same use 0.5% sodium hydroxide solution respectively, with the upper solution of acetate-methanol-water (100:17:13) for developing solvent, launch, exhibition, apart from about 10cm, is taken out, dry, spray, with aluminum chloride test solution, 105 DEG C of heating several minutes, is inspected under putting ultra-violet lamp (365nm).In test sample chromatograph, on the position corresponding to control medicinal material chromatograph, the fluorescence speckle of aobvious same color.
(3) get puerarin reference substance, add methanol and make the solution of every 1mL containing 1mg, product solution in contrast.Test according to thin layer chromatography, draw the need testing solution 10 μ L under (2) item, reference substance solution 5 μ L, put respectively on same silica gel g thin-layer plate, with chloroform-methanol-water (7:2.5:0.25) for developing solvent, launch, take out, dry, put in ammonia steam and smoke 15 minutes, inspect under putting ultra-violet lamp (365nm).In test sample chromatograph, on the position corresponding to control medicinal material chromatograph, the fluorescence speckle of aobvious same color.
(4) get this product 20g, porphyrize, the 50mL that adds water makes dissolving, extracts 2 times with water saturated n-butyl alcohol jolting, each 50mL, merges n-butyl alcohol liquid, washs 2 times, each 50mL with ammonia solution, n-butyl alcohol liquid evaporate to dryness, residue adds ethanol 1mL makes dissolving, as need testing solution.Separately get peoniflorin reference substance, add ethanol and make the solution of every 1mL containing 1mg, product solution in contrast.Test according to thin layer chromatography, draw need testing solution 20 μ L, reference substance solution 10 μ L, put respectively on same silica gel g thin-layer plate, with chloroform-acetate-methanol-formic acid (40:5:10:0.2) for developing solvent, launch, take out, dry, spray with 5% vanillin-sulfuric acid solution, be heated to spot development at 105 DEG C clear.In test sample chromatograph, on the position corresponding to control medicinal material chromatograph, the speckle of aobvious same color.
Every regulation that [inspection] is relevant under should meeting granule item.
[assay] is according to high effective liquid chromatography for measuring.
Chromatographic condition and system suitability take octadecylsilane chemically bonded silica as filler; With acetonitrile-0.1% phosphoric acid solution (12:88) for mobile phase; Determined wavelength is 230nm.Number of theoretical plate calculates should be not less than 2000 by peoniflorin peak.
This product under content uniformity is got in the preparation of need testing solution, mixing, gets appropriate, porphyrize, gets 1g, accurately weighed, put in tool plug conical flask, precision adds Diluted Alcohol 25mL, weighed weight, supersound process 30 minutes, lets cool, more weighed weight, supply the weight of less loss with Diluted Alcohol, shake up, filter, get subsequent filtrate, to obtain final product.
Algoscopy is accurate respectively draws reference substance solution and each 20 μ L of need testing solution, injection liquid chromatography, measures, to obtain final product.
This product every bag in peoniflorin, must not be less than 6.0mg containing the Radix Paeoniae Alba.
Stability testing method
To carry out long-term stable experiment under the terms of packing that goes on the market, temperature 25 DEG C ± 2 DEG C, relative humidity, 60% ± 5%, samples detection level respectively at 0,3,6,9,12,18,24 the end of month.Testing result is as shown in the table:
Peoniflorin result of laboratory test (the content mg in every 15g finished product)
| ? | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 | Reference examples 1 |
| 0 month | 12.5 | 14.1 | 13.6 | 12.8 | 14.4 | 12.5 |
| 3 months | 12.5 | 14.1 | 13.6 | 12.8 | 14.4 | 12.1 |
| 6 months | 12.4 | 14.1 | 13.5 | 12.7 | 14.4 | 11.9 |
| 9 months | 12.3 | 14.0 | 13.4 | 12.7 | 14.3 | 11.4 |
| 12 months | 12.2 | 13.9 | 13.3 | 12.6 | 14.3 | 11.3 |
| 18 months | 12.1 | 13.9 | 13.2 | 12.5 | 14.2 | 11.2 |
| 24 months | 12.1 | 13.8 | 13.2 | 12.5 | 14.2 | 10.9 |
| Degradation rate after 24 months | 3.20％ | 2.12％ | 2.94％ | 2.34％ | 1.39％ | 12.8％ |
Compare with reference examples 1 as can be seen from embodiment, by the improvement to Chinese medicine component extracting process, adopt macroporous adsorbent resin to adsorb, effectively can remove impurity, prevent the degraded of main constituent, improve the stability of granule.
Claims (10)
1. the preparation method of Er'bao granule, is characterized in that: comprise the following steps:
Step 1, with parts by weight, get Radix Pseudostellariae 100 ~ 140 parts, Radix Glehniae 100 ~ 140 parts, 100 ~ 140 parts, Poria, Rhizoma Dioscoreae 100 ~ 140 parts, Fructus Crataegi (parched) 40 ~ 60 parts, Fructus Hordei Germinatus (parched) 40 ~ 60 parts, Pericarpium Citri Reticulatae 40 ~ 60 parts, Radix Paeoniae Alba (parched) 40 ~ 60 parts, Semen Lablab Album (parched) 100 ~ 140 parts, Radix Ophiopogonis 40 ~ 60 parts and roasted RADIX PUERARIAE 40 ~ 60 parts, be ground into coarse powder, decoct with water, filter, merging filtrate;
Step 2, is adsorbed step 1 gained filtrate by macroporous resin, then carries out eluting with ethanol water, obtain eluent, concentrated by eluent, obtain concentrated solution;
Step 3, adds to solid dispersion carrier material in step 2 gained concentrated solution, is stirred to carrier material and dissolves, and except desolventizing also dry, pulverizing, obtains solid dispersion;
Step 4, mixes step 3 gained solid dispersion, diluent, correctives and wetting agent, and granulation, drying, to obtain final product.
2. the preparation method of Er'bao granule according to claim 1, its spy is: step 1 decocts with water in process, and the weight of the water added is 2 ~ 3 times of Chinese medicinal components gross weight.
3. the preparation method of Er'bao granule according to claim 1, its spy is: step 2 big pore adsorption resin is selected from AB-8, NKA, HDP-100, HDP-722 or HDP-750.
4. the preparation method of Er'bao granule according to claim 1, its spy is: in step 2 ethanol water used, ethanol accounting example is 70 ~ 80wt.%.
5. the preparation method of Er'bao granule according to claim 1, its spy is: the relative density of step 2 gained concentrated solution 85 ~ 90 DEG C is 1.2 ~ 1.3.
6. the preparation method of Er'bao granule according to claim 1, its spy is: in step 3, the weight ratio of concentrated solution and carrier material is 1:1 ~ 10.
7. the preparation method of Er'bao granule according to claim 1, its spy is: described carrier material is selected from polyvidone class, copolyvidone class, hydroxypropyl cellulose class, hypromellose class, polyethylene glycols or poloxamer class.
8. the preparation method of Er'bao granule according to claim 1, its spy is: the method except desolventizing in step 3 is drying under reduced pressure.
9. the preparation method of Er'bao granule according to claim 1, its spy is: in step 4, the weight ratio of solid dispersion, diluent, correctives, wetting agent is 100:10 ~ 15:4 ~ 8:0.5 ~ 1.2.
10. the preparation method of Er'bao granule according to claim 1, is characterized in that: described diluent is starch, dextrin, maltose or lactose.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108685845A (en) * | 2018-06-29 | 2018-10-23 | 江西济民可信药业有限公司 | A kind of preparation method of youngster's Bao oral liquid |
| CN114527214A (en) * | 2022-02-22 | 2022-05-24 | 杭州师范大学 | Green extraction method of hydrophobic components in traditional Chinese medicine |
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| CN101590101A (en) * | 2008-05-27 | 2009-12-02 | 孙民富 | A kind of prescription and preparation technology who treats type and complication thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108685845A (en) * | 2018-06-29 | 2018-10-23 | 江西济民可信药业有限公司 | A kind of preparation method of youngster's Bao oral liquid |
| CN114527214A (en) * | 2022-02-22 | 2022-05-24 | 杭州师范大学 | Green extraction method of hydrophobic components in traditional Chinese medicine |
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