CN105030866A - Enteric-coated preparation containing notoginseng triterpenes and preparation method and application of enteric-coated preparation - Google Patents
Enteric-coated preparation containing notoginseng triterpenes and preparation method and application of enteric-coated preparation Download PDFInfo
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Abstract
The invention relates to an enteric-coated preparation containing notoginseng triterpenes and a preparation method of the enteric-coated preparation. The enteric-coated preparation containing notoginseng triterpenes comprises an upper pill core, an isolation layer and an enteric-coated layer, wherein the upper pill core is sequentially coated with the isolation layer and the enteric-coated layer. The pill core comprises, by weight, 40 parts of notoginseng triterpenes, 40-120 parts of blank pellets, 4-8 parts of disintegrant, 2-3.5 parts of adhesive and 3-5 parts of talcum powder. The isolation layer coating is additionally arranged between the enteric-coated layer and the upper pill core so as to enable the surface of the upper pill core to be more smooth, coating is complete, and an enteric coating is easily obtained; notoginseng triterpenes has certain moisture absorption, and the stability of pellets can be improved by additionally arranging the isolation layer coating. In addition, a fluidized bed bottom spraying method is adopted, through formulation optimization, the problem of pellet adhesion caused by the physicochemical property of notoginseng triterpenes is successfully solved, and the high-quality enteric-coated preparation is obtained.
Description
Technical field
The present invention relates to Chinese medicine preparation, be specifically related to enteric coated preparation of a kind of Radix Notoginseng total arasaponins and preparation method thereof and application.
Background technology
Radix Notoginseng total arasaponins (Radix Notoginseng total arasaponins, Notoginsengtriterpenes), cures mainly blood circulation promoting and blood stasis dispelling, promotes blood circulation active.There is the effect of anticoagulant and increase cerebral blood flow, for cerebrovascular sequelae, central retinal vein occlusion, hyphema etc.
Radix Notoginseng total arasaponins from high-quality Radix Notoginseng, extracts effective medicinal ingredient according to extracting and developing technology to comprise more than 20 kind of saponin active substance, 17 kinds of trace element, albumen, abundant vitamin, polysaccharide etc.Wherein, ginsenoside Rg
1and Rb
1accounting for 60-70%, is the main active playing pharmacological action.
At present, market is the medicine of effective ingredient has XUESAITONG PIAN, XUESAITONG JIAONANG, XUESAITONG KELI, XUESAITONG RUANJIAONANG, XUESAITONG ZHUSHEYE with Radix Notoginseng total arasaponins, XUESHUANTONG JIAONANG, XUESHUANTONG ZHUSHEYE, injection XUESHUANTONG (lyophilizing) etc., although XUESAITONG and Xueshuantong preparation are all effective ingredient with Radix Notoginseng total arasaponins, its difference of originating.Radix Notoginseng total arasaponins in XUESAITONG is extracted by Radix Notoginseng reed head and obtains, and the Radix Notoginseng total arasaponins in XUESHUANTONG is extracted by Radix Notoginseng main root, therefore, in respective Radix Notoginseng total arasaponins, the content of contained monomer component is different, and XUESAITONG and XUESHUANTONG can not simply phase trans-substitutions.
No matter be that Radix Notoginseng reed head extracts or Radix Notoginseng main root extracts the Radix Notoginseng total arasaponins obtained, its water solublity is all fine, but saponin molecular weight is relatively bigger than normal (as ginsenoside Rg
1molecular weight is 801, ginsenoside Rb
1molecular weight 1109.3), gastrointestinal tract mucous poor by property, meanwhile, unstable in gastrointestinal tract, destroyed under the effect of gastric acid and enzyme, oral absorption is poor, is the main cause causing current arasaponin oral formulations bioavailability low.
Research finds, Radix Notoginseng total arasaponins principal agent composition R
1, ginsenoside Rg
1, Rb
1oral absolute bioavailability be respectively 1.32%, 1.02% and 1.80%.On the other hand, although injection is rapid-action, there is report some patients to occur anaphylaxis, there is safety issue, and the poor compliance of drug administration by injection patient, be unfavorable for the prolonged application of medicine.
Enteric coated preparation is by the object of enteric material realization in intestinal release, such as Lac, cellulose and its derivates are (as cellulose acetate phthalate, 1,2,4-benzenetricarboxylic acid hydroxypropyl methylcellulose (HPMCT), HPMCAS (HPMCAS)), acrylic resin base polymer (being the family macromolecule polymer of the monomers such as acrylic acid, acrylic acid methyl ester., methacrylic acid and methyl methacrylate according to different proportion copolymerization), polyvinyl acetate phthalic acid ester.And Chinese medicine enteric coated preparation can be divided into small intestinal to locate release pH dependent form and colon site-specific delivery pH dependent form two kinds, classification foundation is that enteric material solute effect under the pH condition of different intestinal juice is different, wherein, small intestinal location release pH dependent form generally selects the polymer that can dissolve at more than pH=5.
Relevant enteric Panax Notoginseng total saponin report has:
CN201210058278.5 (publication number is CN102579536A) discloses the enteric coated preparation of Radix Notoginseng total arasaponins, and its adjuvant is, Radix Notoginseng total arasaponins, starch, dextrin, microcrystalline Cellulose, pregelatinized Starch, magnesium stearate, and coating is enteric coating.
CN201110095431.7 (publication number is CN102166241A) discloses a kind of panax notoginseng saponins enteric microcapsule, its adjuvant comprises Radix Notoginseng total arasaponins 1, enteric material 0.5-10, antiplastering aid 0.03-1, absorption enhancer 0.1-5, and wherein enteric material is polyacrylic resin class, HP-55, cellulose acetate-phthalate, the polyethylene one too in acid esters, Lac, phthalic acid aldehydic acid cellulose, alginate jelly and polyvinyl acetate phthalate; Antiplastering aid is stearate, stearic acid, Pulvis Talci, micropowder silica gel and Polyethylene Glycol; Absorption enhancer is cyclodextrin, chitosan, cholate, fatty acid, glyceride, amino acid derivativges, fatty acyl carnitine class, Borneolum Syntheticum, tween, span, poloxamer, sodium lauryl sulphate and carbomer etc.
About in the prior art of enteric Panax Notoginseng total saponin, process majority is extrusion spheronization method, atresia coating pan preparation method, and problems affect pill content, the release etc. such as easily cause sticky ball, medicine-feeding rate low in preparation process evaluate the index of drug quality.
Based on this, special proposition the present invention.
Summary of the invention
The object of this invention is to provide enteric coated preparation of a kind of Radix Notoginseng total arasaponins and preparation method thereof.
The enteric coated preparation of a kind of Radix Notoginseng total arasaponins provided by the invention, comprises pill core and the sealing coat of coating on described on pill core and enteric layer successively; Described upper pill core comprises the composition of following weight portion: Radix Notoginseng total arasaponins 40 parts, celphere 40-120 part, disintegrating agent 4-8 part, binding agent 2-3.5 part, Pulvis Talci 3-5 part.
Concrete, preferably include the composition of following weight portion in described upper pill core: Radix Notoginseng total arasaponins 40 parts, celphere 80-120 part, disintegrating agent 6-8 part, binding agent 2-3.2 part, Pulvis Talci 3.2-4.8 part.
In the upper pill core of above-mentioned enteric coated preparation:
Described binding agent is the one in hypromellose, hyprolose or PVP K30, preferred hypromellose;
Described disintegrating agent is the one in low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone or carboxymethylstach sodium, preferred low-substituted hydroxypropyl cellulose;
Described celphere is cane sugar type celphere.
In addition, also comprise purified water in the raw material of above-mentioned upper pill core, the consumption of described purified water can be determined according to practical situation, meets the preparation of upper pill core.The desirable consumption of purified water provided by the invention is 400-600 part, preferably 500 parts.
In above-mentioned prescription, raw material Radix Notoginseng total arasaponins PNS has certain hygroscopicity, absorbs its viscosity of a small amount of moisture and just becomes large, be prepared into enteric coated preparation especially in enteric coated pill process at it, moisture is very crucial, and water content is too low, preparation micropill imperfect, containing a small amount of short cylindrical material or powder more, moisture is too high, micropill meeting adhesion, particle diameter becomes large, and particle size range broadens, therefore, the specific adjuvant adding Optimum is needed to carry out the preparation of enteric coated micropill, to improve the quality of the pharmaceutical preparations.
The raw material of sealing coat of the present invention is hypromellose and Pulvis Talci is 3:1-1:1 according to weight ratio, the mixture of preferred 3:2 composition.The separation layer thickness that above-mentioned raw materials is prepared can ensure the impact of medicament contg and release, can not reduce the content of medicine, is that medicine discharges within the standard time.
The raw material of described enteric layer is that especially strange L30D-55, triethyl citrate and Pulvis Talci are the mixture of 10:1:5-20:2:5 according to weight ratio, and the mixture of preferred 10:1:5 or 20:2:5 composition, wherein especially strange L30D-55 is polymer dry weight.Adopt above-mentioned raw materials to prepare enteric layer, medicine can be avoided the stimulation of gastric mucosa, add the stability of medicine, improve drug level, reach the object of small intestinal location release.
It is two-layer that enteric coated preparation of the present invention prepares coating: one deck is sealing coat, one deck is enteric layer.The amount ranges of above-mentioned two-layer raw material can be determined according to the rule of galenic pharmacy by those skilled in the art, but more preferably, the invention provides desirable amount ranges, to provide the quality of the pharmaceutical preparations further, wherein, the raw material dosage of described sealing coat is 60-90 part, and the raw material dosage of described enteric layer is 110-210 part; The raw material dosage of preferred described sealing coat is 70-80 part, and the raw material dosage of described enteric layer is 150-200 part.
The reason that the present invention increases sealing coat coating in the middle of described enteric layer with medicine-feeding label is that on can making, pill wicking surface is more smooth, coatedly more completely be easy to enteric coating, raw material Radix Notoginseng total arasaponins has certain hygroscopicity in addition, increases the stability that sealing coat coating also can improve micropill.
As more preferably technical scheme, enteric coated preparation of the present invention, comprise pill core and the sealing coat of coating on described on pill core and enteric layer successively; Described upper pill core comprises the composition of following weight portion: Radix Notoginseng total arasaponins 40 parts, cane sugar type celphere 40-120 part, binding agent low-substituted hydroxypropyl cellulose 4-8 part, disintegrating agent hypromellose 2-3.5 part, Pulvis Talci 3-5 part, purified water 500 parts; The raw material of described sealing coat is hypromellose and Pulvis Talci is the mixture of 3:1-1:1 composition according to weight ratio, consumption is 60-90 part, and the raw material of described enteric layer is that especially strange L30D-55, triethyl citrate and Pulvis Talci are the mixture of 10:1:5-20:2:5 composition according to weight ratio; Consumption is 110-210 part.
The specification of enteric coated preparation of the present invention can be multiple, if per unit preparation is containing Radix Notoginseng total arasaponins 50mg and 100mg.
Invention also provides the preparation method of above-mentioned enteric coated preparation, the method comprises the following steps:
1) preparation of upper drug solns
Get the purified water of recipe quantity 50-80%, be heated to 45-55 DEG C, slowly add the binding agent of recipe quantity and constantly stir until dissolve, add disintegrating agent, Radix Notoginseng total arasaponins successively, continue stirring until after Radix Notoginseng total arasaponins dissolves completely, then add Pulvis Talci, and keep stirring, and add purified water and be supplemented to full dose, obtain mixed liquor;
2) upper pill core preparation: by step 1) described in mixed liquor spray at the bottom of fluid bed, spray in celphere surperficial, pill core in preparation;
3) coating:
Sealing coat coating solution is prepared: take hypromellose, Pulvis Talci according to proportioning, is mixed with suspension, sprays in fluid bed and carry out coating to described upper pill core by weightening finish 10-15%, dry, molding;
Enteric layer coating solution is prepared: take adjuvant especially strange L30D-55, triethyl citrate, Pulvis Talci according to proportioning, suspension is mixed with by weightening finish 20 ~ 30%, the upper pill core spraying into fluid bed sealing coat to coating carries out secondary coating, dry, obtains enteric coated micropill;
4) molding: by step 3) enteric coated micropill that obtains incapsulates, to obtain final product.
Preferred:
1) preparation of upper drug solns
Get the purified water of recipe quantity 70%, be heated to 50 DEG C, slowly add the binding agent of recipe quantity and constantly stir until dissolve, add disintegrating agent, Radix Notoginseng total arasaponins successively, continue stirring until after Radix Notoginseng total arasaponins dissolves completely, then add Pulvis Talci, and keep stirring, and add purified water and be supplemented to full dose, obtain mixed liquor;
2) upper pill core preparation: by step 1) described in mixed liquor spray at the bottom of fluid bed, spray in celphere surface, hydrojet speed controlling between 7 ~ 10rpm, inlet temperature 45 ~ 55 DEG C, between adjustment atomizing pressure 1.8 ~ 2.2psi, intake is 85 ~ 95m
3upper pill core prepared by/h crosses 24 mesh sieves;
3) coating:
Sealing coat coating solution is prepared: take hypromellose, Pulvis Talci according to proportioning, suspension is mixed with by weightening finish 10-15%, spray in fluid bed with the speed of 2 ~ 4rpm, inlet temperature 40 ~ 50 DEG C, atomizing pressure remains on until coating completes between 1.6 ~ 1.8psi, and dry 5 ~ 10min is convenient to the molding of contagion gown film;
Enteric layer coating solution is prepared: take adjuvant especially strange L30D-55, triethyl citrate, Pulvis Talci according to proportioning, suspension is mixed with by weightening finish 20 ~ 30%, spray in fluid bed with the speed of 3 ~ 5rpm, inlet temperature 40 ~ 45 DEG C, atomizing pressure remains between 1.6 ~ 1.8psi until coating completes, and dry 5 ~ 10min, obtain enteric coated micropill;
4) molding: by step 3) enteric coated micropill that obtains incapsulates, to obtain final product.
In the preparation process of enteric Panax Notoginseng total saponin, main existence is glued ball and is produced the technological difficulties of electrostatic, but inventor successfully solves these technological difficulties by screening prescription consumption and process optimization, the method as reduced its viscosity and optimized device technological parameter by heating medicine-feeding and Coating Solution greatly reduce sticky ball phenomenon generation, by adjusting prescription consumption proportion and significantly improving sealing coat coating time easily produce the phenomenon of electrostatic.Preparation technology of the present invention adopts spray at the bottom of fluid bed finally to prepare enteric coated micropill, compared to additive method as extrusion spheronization method, atresia coating pan preparation method etc., has some advantage:
1) preparation process is continuous, and evenly coated, the integrity of micropill is better;
2) the dispersed one-tenth suspension of supplementary material, the medicine carrying of ball core is even;
3) the technical process used time is shorter, is more suitable for technique and amplifies;
4) micropill rounding property is fine, and particle size distribution is more concentrated.
Possess the preparation method of above advantage, when preparations shaping technical study, then can ensure its success rate better.
Lai Ling etc. refer to Radix Notoginseng total arasaponins enteric coated micropill prepared by celphere in " celphere medicine-feeding legal system is for Radix Notoginseng total arasaponins enteric coated micropill " literary composition, its preparation method is: get PNS9g respectively according to recipe quantity, hydroxypropyl emthylcellulose (HPMC) 0.45g, low-substituted hydroxypropyl cellulose (L-HPC) 0.45g, cross 100 mesh sieve mixings respectively, be dissolved in 60% ethanol, by magnetic stirrer to settled solution, be placed in constant flow pump, and open blade and constantly stir, by preheating of rolling in microcrystalline Cellulose (MCC) celphere to seed-coating machine, the medicine-feeding of whitewashing liquid, to growing up into ball, to complete after medicine-feeding rolling 30min again, take out, 40 DEG C of dryings 6 hours, micropill between screening 18-24 order, obtain.(Lai Ling etc., celphere adds medicine to legal system for Radix Notoginseng total arasaponins enteric coated micropill, Guangxi Medical University's journal, 2011,28 (5): 681-).
Inventor is active component based on Radix Notoginseng total arasaponins, and the celphere for sucrose, microcrystalline Cellulose and starch these three kinds different molding cores has carried out comparative study, mainly screens according to indexs such as technological forming, powder property and year pill core yields.Result shows, each index of sucrose celphere all has obvious advantage, and the application of cane sugar type is also the most widely.
Moreover the present invention is also different from method described in document in preparation method, the present invention adopts spray at the bottom of fluid bed, by formulation optimization, successfully solves the problem causing sticky ball due to Radix Notoginseng total arasaponins physicochemical property.
Present invention also offers the application of above-mentioned enteric Panax Notoginseng total saponin in the medicine of preparation treatment cardiovascular and cerebrovascular disease, cardiovascular and cerebrovascular disease herein comprises the apoplectic hemiplegia that brain network stasis blocking causes, the obstruction of qi in the chest and cardialgia that heart arteries and veins stasis blocking causes; Cerebral infarction, coronary heart diseases and angina pectoris etc., enteric Panax Notoginseng total saponin of the present invention embodies the activity that the bioavailability of highly significant is high, curative effect improves in above-mentioned disease.
The present invention adopts technique scheme, achieves following technique effect in enteric effect angle:
First, the drug loading scope that preparation process of the present invention is suitable for is wider, pill all has good technological feasibility and repeatability than between 1:3 ~ 1:1, and in such enteric coated micropill, the content controlled range of Radix Notoginseng total arasaponins is wider, can realize carrying out capsule charge for different specifications.
Secondly, in enteric coating process, by the proportioning between prescription screening and adjuvant, successfully captured the problem that coating solution easily blocks spray gun and sticky ball, coordinated more ripe technological parameter, technical process is more controlled, stable.
Finally, enteric coated micropill is in vitro in dissolution test, and within 2 hours in 0.1mol/L hydrochloric acid, without release, in the sodium phosphate buffer of pH=6.8, in 30min, release is completely.Very directly illustrate, enteric layer is coated complete and have the good clothing film of plasticity, can discharge completely, illustrate that the investigation for coating weight gain and formulation and technology is comparatively reasonable in buffer solution in 30min.
Accompanying drawing explanation
Fig. 1: embodiment 1 enteric coated micropill release profiles, wherein, abscissa is the time, and unit is minute; Vertical coordinate is release, and unit is %;
Fig. 2: embodiment 2 enteric coated micropill release profiles;
Fig. 3: embodiment 3 enteric coated micropill release profiles;
Fig. 4: comparative example 1 enteric coated micropill release profiles.
Detailed description of the invention
Following examples for illustration of the present invention, but are not used for limiting the scope of the invention.
The source of the Radix Notoginseng total arasaponins in following examples, purchased from Pharmaceutical Jixi, Zhenbao Island branch company, especially strange L30D-55, purchased from Evonik Degussa Specialty Chemicals (Shanghai) Co., Ltd..Other raw materials are the known product that can commercially availablely buy.
Embodiment 1
1, medicine-feeding Core formulation:
| Consumption | |
| Radix Notoginseng total arasaponins (not giving money as a gift not pure) | 40g |
| Celphere (sucrose) | 120g |
| Hypromellose | 3.2g |
| Low-substituted hydroxypropyl cellulose | 8g |
| Pulvis Talci | 4.8g |
| Purified water | To 500ml |
2, preparation technology
1) preparation of upper drug solns
Get the purified water of recipe quantity 70%, be heated to 50 DEG C, slowly add the hypromellose of recipe quantity and constantly stir until dissolve, add low-substituted hydroxypropyl cellulose, Radix Notoginseng total arasaponins successively, continue stirring until after Radix Notoginseng total arasaponins dissolves completely, add Pulvis Talci again, and keep stirring, and add purified water and be supplemented to full dose;
2) upper pill core preparation: by step 1) mixed liquor spray at the bottom of fluid bed, spray in celphere surperficial, the ratio of Radix Notoginseng total arasaponins and celphere is 1:3, and the upper pill core of preparation crosses 24 mesh sieves;
3) coating:
Sealing coat coating solution is prepared: take hypromellose, Pulvis Talci (weight ratio is 3:2) as coating material according to proportioning, be mixed with suspension 82g for subsequent use by weightening finish 12%.Spray in fluid bed by coating solution with the speed of 2 ~ 4rpm, inlet temperature 50 DEG C, atomizing pressure remains on until coating completes between 1.6 ~ 1.8psi, and dry 5 ~ 10min is convenient to the molding of contagion gown film;
Enteric layer coating solution is prepared: take especially strange L30D-55, triethyl citrate, Pulvis Talci (weight ratio is 10:1:5) according to proportioning, be mixed with suspension 203g for subsequent use by weightening finish 30%.Spray in fluid bed by coating solution with the speed of 3 ~ 5rpm, inlet temperature 40 DEG C, atomizing pressure remains on until coating completes between 1.6 ~ 1.8psi, and dry 5 ~ 10min is convenient to enteric coated micropill molding.
4) molding: by step 3) micropill that obtains loads in 2# gelatin hollow capsule.
Embodiment 2
1, medicine-feeding Core formulation:
| Consumption | |
| Radix Notoginseng total arasaponins (not giving money as a gift not pure) | 40g |
| Celphere (sucrose) | 80g |
| Hypromellose | 2g |
| Polyvinylpolypyrrolidone | 4g |
| Pulvis Talci | 3.2g |
| Purified water | To 500ml |
2, preparation technology
1) preparation of upper drug solns
Get the purified water of recipe quantity 70%, be heated to 50 DEG C, slowly add the hypromellose of recipe quantity and constantly stir until dissolve, add polyvinylpolypyrrolidone, Radix Notoginseng total arasaponins successively, continue stirring until after Radix Notoginseng total arasaponins dissolves completely, add Pulvis Talci again, and keep stirring, and add purified water and be supplemented to full dose;
2) upper pill core preparation: by step 1) mixed liquor spray at the bottom of fluid bed, spray in celphere surperficial, the ratio of Radix Notoginseng total arasaponins and celphere is 1:2, and the upper pill core of preparation crosses 24 mesh sieves;
3) coating:
Sealing coat coating solution is prepared: take hypromellose Pulvis Talci (weight ratio is 3:2) as coating material according to proportioning, be mixed with suspension 63g for subsequent use by weightening finish 10%.Spray in fluid bed by coating solution with the speed of 2 ~ 4rpm, inlet temperature 50 DEG C, atomizing pressure remains on until coating completes between 1.6 ~ 1.8psi, and dry 5 ~ 10min is convenient to the molding of contagion gown film;
Enteric layer coating solution is prepared: take especially strange L30D-55, triethyl citrate, Pulvis Talci (weight ratio is 10:1:5) according to proportioning, be mixed with suspension 189g for subsequent use by weightening finish 30%.Spray in fluid bed by coating solution with the speed of 3 ~ 5rpm, inlet temperature 40 DEG C, atomizing pressure remains on until coating completes between 1.6 ~ 1.8psi, and dry 5 ~ 10min is convenient to enteric coated micropill molding.
4) molding: by step 3) micropill that obtains loads in 2# gelatin hollow capsule.
Embodiment 3
1, medicine-feeding Core formulation:
| Consumption | |
| Radix Notoginseng total arasaponins (not giving money as a gift not pure) | 40g |
| Celphere (sucrose) | 40g |
| Hypromellose | 2.8g |
| Sodium carboxymethylstarch | 6g |
| Pulvis Talci | 4g |
| Purified water | To 500ml |
2, preparation technology
1) preparation of upper drug solns
Get the purified water of recipe quantity 70%, be heated to 50 DEG C, slowly add the hypromellose of recipe quantity and constantly stir until dissolve, add sodium carboxymethylstarch, Radix Notoginseng total arasaponins successively, continue stirring until after Radix Notoginseng total arasaponins dissolves completely, add Pulvis Talci again, and keep stirring, and add purified water and be supplemented to full dose;
2) upper pill core preparation: by step 1) mixed liquor spray at the bottom of fluid bed, spray in celphere surperficial, the ratio of Radix Notoginseng total arasaponins and celphere is 1:1, and the upper pill core of preparation crosses 24 mesh sieves;
3) coating: sealing coat coating solution is prepared: take hypromellose, Pulvis Talci (weight ratio is 3:2) as coating material according to proportioning, be mixed with suspension 89g for subsequent use by weightening finish 15%.Spray in fluid bed by coating solution with the speed of 2 ~ 4rpm, inlet temperature 50 DEG C, atomizing pressure remains on until coating completes between 1.6 ~ 1.8psi, and dry 5 ~ 10min is convenient to the molding of contagion gown film;
Enteric layer coating solution is prepared: take especially strange L30D-55, triethyl citrate, Pulvis Talci (weight ratio is 20:2:5) according to proportioning, be mixed with suspension 119g for subsequent use by weightening finish 20%.Spray in fluid bed by coating solution with the speed of 3 ~ 5rpm, inlet temperature 40 DEG C, atomizing pressure remains on until coating completes between 1.6 ~ 1.8psi, and dry 5 ~ 10min is convenient to enteric coated micropill molding.
4) molding: by step 3) micropill that obtains loads in 2# gelatin hollow capsule.
Comparative example 1:
Enteric coated micropill sample is prepared by the prescription in document " celphere medicine-feeding legal system is for Radix Notoginseng total arasaponins enteric coated micropill " literary composition and preparation method.
Experimental example 1: micropill content
Micropill content is in Rg1, R1, Re, Rb1, Rd five compositions, and content assaying method is according to XUESHUANTONG JIAONANG content assaying method.
Measure according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 annex VI D).
1, chromatographic condition and system suitability are filler with octadecylsilane chemically bonded silica, are mobile phase A with acetonitrile, take water as Mobile phase B, carry out gradient elution by the regulation in table 1; Flow velocity is per minute is 1.5ml; Determined wavelength is 203nm; Column temperature 25 DEG C.The separating degree of ginsenoside Rg1 and ginsenoside Re should be greater than 1.5.Number of theoretical plate calculates should be not less than 6000 by ginsenoside Rg1 peak.
Table 1 mobile phase time gradient table
2, the preparation of reference substance mixed solution: take Radix Notoginseng total arasaponins and be about 50mg, adds methanol constant volume in 10ml measuring bottle, shakes up, to obtain final product.
3, the preparation of need testing solution: take test sample and be about 0.6g, adds methanol constant volume in 100ml measuring bottle, shakes up, and filters, gets subsequent filtrate, to obtain final product.
4, algoscopy: accurate absorption reference substance mixed solution and each 10 μ l of need testing solution respectively, injection liquid chromatography, measures, to obtain final product.
5, result of the test: in table 2.
Table 2 enteric coated micropill assay result
Result shows: ball core medicine carrying ratio (Radix Notoginseng total arasaponins: celphere) of the present invention is by 1:1-1:3 preparation, and content meets product requirement, medicine-feeding rate is high.
Experimental example 2: dissolution test
1, research method
Get Radix Notoginseng total arasaponins enteric coated micropill (embodiment 1,2,3, comparative example 1) appropriate, make enteric coated capsule.Measure by " Chinese Pharmacopoeia " 2010 editions second annex XD drug release determination method second method.
2, drug release determination result: in table 3.Release profiles is shown in Fig. 1,2,3,4.
Table 3 enteric coated micropill Accumulation dissolution
4, conclusion
Result shows: 120min is without release in acid for enteric Panax Notoginseng total saponin of the present invention, and in the buffer of pH6.8, release 15min discharges substantially completely.And to compare with comparative example 1 release time short, discharge more complete.Meet enteric coated preparation standard.
Although above with general explanation, detailed description of the invention and test, the present invention is described in detail, and on basis of the present invention, can make some modifications or improvements it, this will be apparent to those skilled in the art.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, all belong to the scope of protection of present invention.
Claims (10)
1. an enteric coated preparation for Radix Notoginseng total arasaponins, is characterized in that, comprises pill core and the sealing coat of coating on described on pill core and enteric layer successively; Described upper pill core comprises the composition of following weight portion: Radix Notoginseng total arasaponins 40 parts, celphere 40-120 part, disintegrating agent 4-8 part, binding agent 2-3.5 part, Pulvis Talci 3-5 part.
2. enteric coated preparation according to claim 1, is characterized in that, described upper pill core comprises the composition of following weight portion: Radix Notoginseng total arasaponins 40 parts, celphere 80-120 part, disintegrating agent 6-8 part, binding agent 2-3.2 part, Pulvis Talci 3.2-4.8 part.
3. enteric coated preparation according to claim 1 and 2, is characterized in that, described binding agent is the one in hypromellose, hyprolose or PVP K30.
4. enteric coated preparation according to claim 1 and 2, is characterized in that, described disintegrating agent is the one in low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone or carboxymethylstach sodium.
5. the enteric coated preparation according to any one of claim 1-4, is characterized in that, the raw material of described sealing coat is hypromellose and Pulvis Talci is the mixture of 3:1-1:1 composition according to weight ratio.
6. the enteric coated preparation according to any one of claim 1-4, is characterized in that, the raw material of described enteric layer is that especially strange L30D-55, triethyl citrate and Pulvis Talci are the mixture of 10:1:5-20:2:5 composition according to weight ratio.
7. the enteric coated preparation according to any one of claim 1-6, is characterized in that, the raw material dosage of described sealing coat is 60-90 part, and the raw material dosage of described enteric layer is 110-210 part.
8. enteric coated preparation according to claim 1, is characterized in that, comprises pill core and the sealing coat of coating on described on pill core and enteric layer successively; Described upper pill core comprises the composition of following weight portion: Radix Notoginseng total arasaponins 40 parts, cane sugar type celphere 40-120 part, disintegrating agent low-substituted hydroxypropyl cellulose 4-8 part, binding agent hypromellose 2-3.5 part, Pulvis Talci 3-5 part, purified water 500 parts; The raw material of described sealing coat is hypromellose and Pulvis Talci is the mixture of 3:1-1:1 composition according to weight ratio, consumption is 60-90 part, and the raw material of described enteric layer is that especially strange L30D-55, triethyl citrate and Pulvis Talci are the mixture of 10:1:5-20:2:5 composition according to weight ratio; Consumption is 110-210 part.
9. the preparation method of enteric coated preparation described in any one of claim 1-8, is characterized in that, comprise the steps:
1) preparation of upper drug solns
Get the purified water of recipe quantity 50-80%, be heated to 45-55 DEG C, slowly add the binding agent of recipe quantity and constantly stir until dissolve, add disintegrating agent, Radix Notoginseng total arasaponins successively, continue stirring until after Radix Notoginseng total arasaponins dissolves completely, then add Pulvis Talci, and keep stirring, and add purified water and be supplemented to full dose, obtain mixed liquor;
2) upper pill core preparation: by step 1) described in mixed liquor spray at the bottom of fluid bed, spray in celphere surperficial, pill core in preparation;
3) coating:
Sealing coat coating solution is prepared: take hypromellose, Pulvis Talci according to proportioning, is mixed with suspension, sprays in fluid bed and carry out coating to described upper pill core by weightening finish 10-15%, dry, molding;
Enteric layer coating solution is prepared: take adjuvant especially strange L30D-55, triethyl citrate, Pulvis Talci according to proportioning, suspension is mixed with by weightening finish 20 ~ 30%, the upper pill core spraying into fluid bed sealing coat to coating carries out secondary coating, dry, obtains enteric coated micropill;
4) molding: by step 3) enteric coated micropill that obtains incapsulates, to obtain final product;
Preferred:
1) preparation of upper drug solns
Get the purified water of recipe quantity 70%, be heated to 50 DEG C, slowly add the binding agent of recipe quantity and constantly stir until dissolve, add disintegrating agent, Radix Notoginseng total arasaponins successively, continue stirring until after Radix Notoginseng total arasaponins dissolves completely, then add Pulvis Talci, and keep stirring, and add purified water and be supplemented to full dose, obtain mixed liquor;
2) upper pill core preparation: by step 1) described in mixed liquor spray at the bottom of fluid bed, spray in celphere surface, hydrojet speed controlling between 7 ~ 10rpm, inlet temperature 45 ~ 55 DEG C, between adjustment atomizing pressure 1.8 ~ 2.2psi, intake is 85 ~ 95m
3upper pill core prepared by/h crosses 24 mesh sieves;
3) coating:
Sealing coat coating solution is prepared: take hypromellose, Pulvis Talci according to proportioning, suspension is mixed with by weightening finish 10-15%, spray in fluid bed with the speed of 2 ~ 4rpm, inlet temperature 40 ~ 50 DEG C, atomizing pressure remains on until coating completes between 1.6 ~ 1.8psi, and dry 5 ~ 10min is convenient to the molding of contagion gown film;
Enteric layer coating solution is prepared: take adjuvant especially strange L30D-55, triethyl citrate, Pulvis Talci according to proportioning, suspension is mixed with by weightening finish 20 ~ 30%, spray in fluid bed with the speed of 3 ~ 5rpm, inlet temperature 40 ~ 45 DEG C, atomizing pressure remains between 1.6 ~ 1.8psi until coating completes, and dry 5 ~ 10min, obtain enteric coated micropill;
4) molding: by step 3) enteric coated micropill that obtains incapsulates, to obtain final product.
10. the application of enteric Panax Notoginseng total saponin described in any one of claim 1-8 in the medicine of preparation treatment cardiovascular and cerebrovascular disease.
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| CN112315991A (en) * | 2020-12-10 | 2021-02-05 | 西双版纳华坤生物科技有限责任公司 | Pharmaceutical composition for treating thromboembolism, preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102166241A (en) * | 2011-04-15 | 2011-08-31 | 刘华钢 | Panax notoginseng saponins enteric microcapsule |
| CN102579536A (en) * | 2012-03-07 | 2012-07-18 | 云南维和药业股份有限公司 | Enteric Panax Notoginseng total saponin preparation and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102166241A (en) * | 2011-04-15 | 2011-08-31 | 刘华钢 | Panax notoginseng saponins enteric microcapsule |
| CN102579536A (en) * | 2012-03-07 | 2012-07-18 | 云南维和药业股份有限公司 | Enteric Panax Notoginseng total saponin preparation and preparation method thereof |
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| 赖玲等: "空白丸芯上药法制备三七总皂苷肠溶微丸", 《空白丸芯上药法制备三七总皂苷肠溶微丸》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112315991A (en) * | 2020-12-10 | 2021-02-05 | 西双版纳华坤生物科技有限责任公司 | Pharmaceutical composition for treating thromboembolism, preparation method and application thereof |
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