CN102526233A - Multi-unit enteric-coated preparation containing aconitine and preparation method thereof - Google Patents
Multi-unit enteric-coated preparation containing aconitine and preparation method thereof Download PDFInfo
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- CN102526233A CN102526233A CN2010106052139A CN201010605213A CN102526233A CN 102526233 A CN102526233 A CN 102526233A CN 2010106052139 A CN2010106052139 A CN 2010106052139A CN 201010605213 A CN201010605213 A CN 201010605213A CN 102526233 A CN102526233 A CN 102526233A
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Abstract
The invention discloses an aconitine medicinal multi-unit enteric-coated capsule or a multi-unit enteric-coated tablet and a preparation method thereof. A micro-pill consists of hollow pill cores and a coating layer coated outside the hollow pill cores, wherein the coating layer comprises a main medicament layer consisting of a main medicament and auxiliary materials, an isolating layer coated outside the main medicament layer, and an enteric-coated layer coated outside the isolating layer. After a product is treated with a preparation process, the main medicament is not released basically in acids but is released after entering small intestines, so that untoward effects caused by the stimulation of the main medicament on the stomach are avoided. Meanwhile, the phenomenon of excessively high local medicament concentration caused by sudden release of aconitine is avoided simultaneously, and food influence is avoided.
Description
Technical field
The present invention relates to the field of Chinese medicines, more specifically, is a kind of multiple-unit enteric coated preparation that contains aconitine and preparation method thereof.
Background technology
Aconitine is the aconite alkaloids of from Ranunculaceae aconitum plant (Aconitum), separating, and has the easing pain and diminishing inflammation effect, is mainly used in diseases such as treatment rheumatism, rheumatoid and osteoarthritis.Its preparation comprises injection, oral liquid, tablet.Often with having an intense pain and the redness of injection site, patient's compliance is poor in use for injection; Common oral liquid take the back oral cavity numb, to digestive tract particularly stomach strong impulse is arranged; Common oral solid formulation is taken the back through upper digestive tract disintegrate, absorption.The same with oral liquid, aconitine under intensive gastric acid condition, facile hydrolysis and the effective ingredient of degrading; In addition, be prone to generate salt in the gastric acid reaction bioavailability is reduced, the comprehensive function meeting of these two factors reduces the effectiveness of aconitine oral formulations.Have data to show, disperse not open for the conventional tablet aconitine, the too high meeting of local concentration intense stimulus mucosa and other tissue produce untoward reaction such as calcination.Granted publication number is a kind of enteric-coated quick releasing sheet that contains aconitine of CN 100518721C and preparation method thereof; Aconitine is processed enteric coatel tablets; Attempt is exempted medicine to the stimulation of stomach and avoid the medicine inactivation that all or part of decomposition causes in gastric juice; But experiment shows that common enteric coatel tablets can not be exempted the stimulation to intestinal.Analyze its reason, after in intestinal, discharging, cause local concentration too high and cause zest, even cause intestinal ulcer intestinal.
Summary of the invention
The object of the invention is to provide a kind of multiple-unit enteric coated preparation that contains aconitine and preparation method thereof, and said preparation has overcome the possible prominent phenomenon of releasing of enteric coatel tablets, and no local drug concentration is too high, the influence of unable to take food thing.
Above-mentioned purpose is to realize through following technical scheme:
Said preparation is incapsulated by a plurality of enteric coated micropills that independently comprise aconitine or enteric coated micropill and suitable adjuvant are pressed into the multiple-unit pellet tablet and process.Described enteric coated micropill adds coatings by celphere and forms.
Described coatings comprises the principal agent layer that contains principal agent and various adjuvants, and principal agent and enteric material are interactional to be wrapped in the outer sealing coat of principal agent layer and to be wrapped in beyond the sealing coat to reach the enteric layer of enteric effect in order to reduce;
The composition and the percentage by weight of described principal agent layer comprise:
Principal agent 0.1%～40%
Water-solubility carrier 4%～80%
Diluent 0%～50%
Antiplastering aid 0～30%
Described principal agent comprises bulleyaconitine A, 3-ethyl aconitine and lappaconitine hydrobromide, preferred bulleyaconitine A.
Described water-solubility carrier is selected from one or more in polyvinylpyrrolidone, hydroxypropyl methylcellulose, poloxamer and the Polyethylene Glycol etc.;
Described diluent is selected from a kind of in mannitol, dextran, galactose, lactose and the sucrose or more than one;
Described antiplastering aid is a field of medicaments adjuvant commonly used, optional Pulvis Talci, micropowder silica gel or magnesium stearate a kind of or more than one;
Described sealing coat purpose is the interaction of enteric polymer in inhibition principal agent and the enteric layer, thereby improves stability of formulation.
The component and the weight percent content of sealing coat comprise:
Water-soluable gel material 10～90%
Plasticizer 0～20%
Defoamer 0～15%
Antiplastering aid 0～50%
Opacifier 0～10%
Selected water-soluable gel material is selected from the mixture of a kind of of hydroxypropyl emthylcellulose or polyvinylpyrrolidone or two kinds.Hyprolose can be high molecular polymer coating material and the premix powder thereof of commercial obtainable Opadry
Opatint
Opaspray
Opalux
etc., preferred hydroxypropyl methylcellulose.
Said plasticizer is selected from but is not limited to triethyl citrate, ATEC, tributyl 2-acetylcitrate, dibutyl sebacate, Dibutyl phthalate, glycerol, triacetin, monoacetin, cochin oil, Polyethylene Glycol, propylene glycol, diethyl phthalate, Tween-80, Semen Ricini wet goods, can be above-mentioned one or more combination; Described defoamer not necessarily will add in prescription, sees the concrete condition in the technical process and decides, and generally uses dimethicone.Described antiplastering aid comprises one or both in sliding ancient powder, micropowder silica gel or the magnesium stearate.Medicinal pigments such as opacifier titanium dioxide, iron oxide yellow, iron oxide red.
The component and the weight ratio of described enteric layer comprise:
Enteric layer material 20～100%
Plasticizer 0～20%
Defoamer 0～25%
Antiplastering aid 0～50%
Opacifier 0～10%
Said enteric coat layer is dissolved in appropriate solvent or the disperse medium by the enteric coatings material to be processed; Enteric-coating material is selected from but is not limited to crylic acid resin, p-phthalic acid hydroxypropyl emthylcellulose and Cellacefate, SA-M, enteric Opadry; Eudragit E 30D-55; Eudragit RL 30D etc. can be above-mentioned one or more combination.
According to one of scheme of the present invention, also comprise being wrapped in the outer layer protective layer of enteric layer.Used adjuvant of protective layer and percentage by weight thereof and sealing coat are similar.Be not every kind of situation layer that all needs protection, but protective layer generally can improve outward appearance, the feel of product, the stability and the machining property of storage, but also can improve some other performance.Like final products is multiple-unit micropill tablet, and the bag protective layer is necessary, is that micropill breaks to avoid at tabletting.
The diameter of described micropill is 0.5～1.5mm, and the diameter of celphere is 0.2～0.8mm.
The method for preparing of micropill of the present invention comprises the steps:
(1) adopt method well known in the art to prepare blank micropill or adopt commercially available celphere;
(2) principal agent, water-solubility carrier, diluent, antiplastering aid are dissolved in the ethanol water, then celphere are carried out coating in above-mentioned solution, obtain to have the micropill of principal agent layer;
The micropill that (3) will have the principal agent layer is at the coating solution coating of being made up of water-soluable gel material, plasticizer, defoamer, antiplastering aid and opacifier and ethanol water;
(4), promptly obtain the enteric coated micropill of invention again with above-mentioned product coating in by enteric-coating material, plasticizer, defoamer, antiplastering aid, opacifier and ethanol water mixing coating solution.
(5) as required, can adopt the conventional method packing protective layer with micropill to intestinal.
Adopt method well known in the art, can process the multiple-unit pellet tablet with described micropill preparation becoming capsule or with micropill and suitable adjuvant.
A kind of multiple-unit enteric coated preparation that contains aconitine of the present invention and preparation method thereof is owing to add the enteric coatings material in coatings; Improved the interior release behavior of body of medicine greatly; Increase medicine stability in vivo, avoided the degraded of aconitine in gastric acid, improved therapeutic effect.On the other hand; Product comprises a plurality of enteric coated micropills that independently have pharmacologically active; Each micropill can both play a role separately again; So also have following advantage: (1) is owing to being a plurality of administrations unit, even the medicine " prominent releasing " that occurs in the individual elements body can obviously not influence the whole effect of medicine, " all or none " phenomenon that has often occurred when having avoided the single dose administration yet; (2) medicine can be evenly dispersed in the small intestinal, thereby the difference that in Different Individual, discharges, absorbs is very little, and it is wide to be suitable for the crowd; (3) dispersed and distributed of medicine has also obviously reduced a certain partial stimulation, and untoward reaction obviously alleviates.Be the multiple-unit enteric coated preparation of aconitine of the present invention, have that no medicine is prominent releases advantages such as phenomenon, the too high phenomenon of no local drug concentration, unable to take food thing influence, medicine plays a role fully, untoward reaction is light, therapeutic effect is fairly obvious.In addition, the patient for the tablet that is difficult for swallowing can pour the micropill in the capsule in the fruit juice into and take together, be specially adapted in go into always, women and child patient.
The specific embodiment:
Below embodiment in provided prescription and the preparation technology of several kinds of different enteric coated capsulees or multiple-unit enteric coatel tablets by aforementioned summary of the invention.All can provide 1000 capsules of preparation or needed each adjuvant of tablet and consumption thereof when each instance begins, in the back preparation process described then, provide required equipment.The release degree adopts Chinese Pharmacopoeia 2010 editions, and second method (being used for enteric coated preparation) of appendix XC dissolution method is tested.
Below in conjunction with embodiment the present invention is done further to state clearly in detail, but be not to be to further qualification of the present invention, foregoing according to the present invention is made other forms of change, replacement etc. and is all belonged to scope of the present invention.
Embodiment 1:
Bulleyaconitine A enteric coated capsule (1000)
Get the raw materials ready according to following prescription, pulverize crude drug and various pharmaceutic adjuvant, cross 100 mesh sieves.
Medicine carrying micropill: gram
Bulleyaconitine A (principal agent) 0.4
Sucrose ball 70
Polyvinylpyrrolidone (water-solubility carrier) 20
Lactose (diluent) 4.0
Pulvis Talci (antiplastering aid) 5
Ethanol (solvent) is an amount of
The isolation coat layer:
Hydroxypropyl methylcellulose (water-soluable gel material) 2
Polyethylene Glycol (plasticizer) 0.4
Pulvis Talci (antitackiness agent) 2
Water (disperse medium) is an amount of
Enteric coat layer:
Polyacrylic resin (Eudragit L 30D-55) (enteric coatings material) 25
Pulvis Talci (antiplastering aid) 14
Dimethicone 1
Triethyl citrate (plasticizer) 5
Water (disperse medium) is an amount of
Bag drug-loaded layer: polyvinylpyrrolidone is dissolved in the adequate amount of ethanol solution, adds the bulleyaconitine A of recipe quantity, treat that its dissolving back adds lactose, treat to add Pulvis Talci again after its dissolving, stir, promptly get principal cartridge clothing layer liquid.Under the lasting stirring of magnetic stirrer, in fluid bed, carry out coating operation, after coating is accomplished dry several minutes.
The bag sealing coat: with hydroxypropyl methylcellulose and Pulvis Talci, Polyethylene Glycol is dissolved in and makes the isolation coat liquid with buffer action in the suitable quantity of water, under the lasting stirring of magnetic stirrer, carries out coating with fluid bed;
Bag enteric layer: Eudragit L 30D-55 is dispersed in the suitable quantity of water,, stirs, make enteric coating liquid to wherein slowly adding the Pulvis Talci of homogenize, triethyl citrate and dimethicone in water; The medicine carrying micropill that wraps sealing coat for preparing is placed in the fluid bed, spray into Eudragit L 30D-55 enteric coating liquid continuously, limit spray coating solution, the limit blowing hot-air promptly arrives the enteric coated micropill of bulleyaconitine A.
The preparation of enteric coated capsule: the enteric coated micropill filling that makes is promptly got the bulleyaconitine A enteric coated capsule in capsule.
Embodiment 2:
3-acetylaconitine enteric coated capsule (1000)
Get the raw materials ready according to following prescription, pulverize crude drug and various pharmaceutic adjuvant, cross 100 mesh sieves.
Medicine carrying micropill: gram
3-acetylaconitine (principal agent) 1
Starch ball 60
Polyethylene Glycol (water-solubility carrier) 6
Lactose (diluent) 4
Pulvis Talci (antiplastering aid) 8
Ethanol (solvent) is an amount of
The isolation coat layer:
Hydroxypropyl methylcellulose (water-soluable gel material) 2
Polyethylene Glycol (plasticizer) 0.8
Pulvis Talci (antiplastering aid) 2
Titanium dioxide (opacifier) 1
Water (disperse medium) is an amount of
Enteric coat layer:
Enteric Opadry (enteric coatings material) 25
Pulvis Talci (antiplastering aid) 3
Triethyl citrate (plasticizer) 0.8
Water (disperse medium) is an amount of
The bag drug-loaded layer: the Polyethylene Glycol of recipe quantity is dissolved in an amount of ethanol, adds the 3-acetylaconitine of recipe quantity, treat that it dissolves back roller and goes into lactose, the dissolving back adds Pulvis Talci, and stirring promptly gets principal agent layer coating solution.The use fluid bed carries out coating operation under the lasting stirring of magnetic stirrer, and coating is accomplished back drying several minutes in fluid bed.
Bag sealing coat: with hydroxypropyl methylcellulose, Pulvis Talci, titanium dioxide and Polyethylene Glycol, be dissolved in and make isolation coat liquid in the suitable quantity of water, under the lasting stirring of magnetic stirrer, carry out coating with fluid bed with buffer action;
Enteric-coating layer: the enteric Opadry is dispersed in the suitable quantity of water,, stirs, make enteric coating liquid to wherein slowly adding the Pulvis Talci of homogenize and triethyl citrate in water; The medicine carrying micropill for preparing is placed in fluid bed or other coating equipment, spray into enteric Opadry coating solution continuously, limit spray coating solution, limit blowing hot-air, i.e. 3-acetylaconitine enteric coated micropill, after coating is accomplished dry several minutes.
The preparation of enteric coated capsule: the enteric coated micropill filling that makes is promptly got the 3-acetylaconitine enteric coated capsule in capsule.
Embodiment 3:
Lappaconitine hydrobromide enteric coated capsule (1000)
Get the raw materials ready according to following prescription, pulverize crude drug and various pharmaceutic adjuvant, cross 100 mesh sieves.
Medicine carrying core body: g
Lappaconitine hydrobromide (principal agent) 6
Microcrystalline Cellulose micropill 50
Polyethylene Glycol (water-solubility carrier) 7
Pulvis Talci (antiplastering aid) 4.5
Ethanol (solvent) is an amount of
The isolation coat layer:
Hydroxypropyl methylcellulose (water-soluable gel material) 4
Polyethylene Glycol (plasticizer) 1.6
Pulvis Talci (antiplastering aid) 4
Water (disperse medium) 192
Enteric coat layer:
Polyacrylic resin (Eudragit L 30D-55) (enteric coatings material) 50
Pulvis Talci (antiplastering aid) 10
Triethyl citrate (plasticizer) 2
Water (disperse medium) is an amount of
The bag drug-loaded layer: the Polyethylene Glycol of recipe quantity is dissolved in an amount of ethanol, adds the lappaconitine hydrobromide of recipe quantity, the dissolving back adds Pulvis Talci, stirs, and promptly gets principal agent layer coating solution.The use fluid bed carries out coating operation under the lasting stirring of magnetic stirrer, and coating is accomplished back drying several minutes in fluid bed.
Bag sealing coat: with hydroxypropyl methylcellulose and Pulvis Talci, Polyethylene Glycol, be dissolved in and make isolation coat liquid in the suitable quantity of water, under the lasting stirring of magnetic stirrer, carry out coating with fluid bed with buffer action;
Bag enteric layer: Eudragit L 30D-55 is dispersed in the suitable quantity of water,, stirs, make enteric coating liquid to wherein slowly adding the Pulvis Talci of homogenize and triethyl citrate in water; The medicine carrying micropill for preparing is placed fluid bed, spray into Eudragit L 30D-55 enteric coating liquid continuously, limit spray coating solution, the limit blowing hot-air promptly arrive the lappaconitine hydrobromide enteric coated micropill, after the coating completion dry several minutes.
The preparation of enteric coated capsule: the lappaconitine hydrobromide enteric coated micropill filling that makes is promptly got the lappaconitine hydrobromide enteric coated capsule in capsule.
Embodiment 4:
Bulleyaconitine A enteric coated capsule (1000)
Get the raw materials ready according to following prescription, pulverize crude drug and various pharmaceutic adjuvant, cross 100 mesh sieves.
Medicine carrying core body: gram
Bulleyaconitine A (principal agent) 1
Microcrystalline Cellulose micropill 120
Poloxamer (water-solubility carrier 4
Sucrose (diluent) 3.8
Pulvis Talci (antiplastering aid) 5
In right amount
The isolation coat layer:
Hydroxypropyl methylcellulose (water-soluable gel material) 14
Glycerol (plasticizer) 4.8
Pulvis Talci (antiplastering aid) 14
Water (disperse medium) is an amount of
Enteric coat layer:
Polyacrylic resin (Eudragit L 30D-55) (enteric coatings material) 130
Pulvis Talci (antiplastering aid) 35
Triethyl citrate (plasticizer) 8.9
Water (disperse medium) is an amount of
The bag drug-loaded layer: the poloxamer of recipe quantity is dissolved in an amount of ethanol, adds the bulleyaconitine A of recipe quantity, treat that its dissolving back adds sucrose, the dissolving back adds Pulvis Talci, stirs, and promptly gets principal agent layer coating solution.The use fluid bed carries out coating operation under the lasting stirring of magnetic stirrer, and coating is accomplished back drying several minutes in fluid bed.
The bag sealing coat: with hydroxypropyl methylcellulose and Pulvis Talci, glycerol, be dissolved in make in the suitable quantity of water have buffer action isolation coat liquid under the lasting stirring of magnetic stirrer, carry out coating with fluid bed;
Enteric-coating layer: Eudragit L 30D-55 is dispersed in the suitable quantity of water,, supplies the prescription water gaging, stir, make enteric coating liquid to wherein slowly adding the Pulvis Talci of homogenize and triethyl citrate in water; The medicine carrying micropill for preparing is placed in the sugar-coat ball, spray into Eudragit L 30D-55 enteric coating liquid continuously, limit spray coating solution, the limit blowing hot-air promptly obtains the bulleyaconitine A enteric coated micropill.
The preparation of enteric coated capsule: the bulleyaconitine A enteric coated micropill filling that makes is promptly got the bulleyaconitine A enteric coated capsule in capsule.
Embodiment 5:
Bulleyaconitine A multiple-unit pellet tablet (1000)
Get the raw materials ready according to following prescription, pulverize crude drug and various pharmaceutic adjuvant, cross 100 mesh sieves.
Medicine carrying micropill: gram
Bulleyaconitine A (principal agent) 0.4
Sucrose ball 70
Polyvinylpyrrolidone (water-solubility carrier) 20
Lactose (diluent) 4
Pulvis Talci (antiplastering aid) 20
Ethanol (solvent) is an amount of
The isolation coat layer:
Hydroxypropyl methylcellulose (water-soluable gel material) 2
Polyethylene Glycol (plasticizer) 0.8
Pulvis Talci (antiplastering aid) 2
Water (disperse medium) is an amount of
Enteric coat layer:
Polyacrylic resin (Eudragit L 30D-55) (enteric coatings material) 23
Pulvis Talci (antiplastering aid) 10
Diethyl phthalate (plasticizer) 0.8
Water (disperse medium) is an amount of
Protective layer
Hydroxypropyl methylcellulose (water-soluable gel material) 3
Polyethylene Glycol (plasticizer) 1g
Pulvis Talci (antiplastering aid) 2g
Water (disperse medium) is an amount of
Bag drug-loaded layer: polyvinylpyrrolidone is dissolved in the adequate amount of ethanol solution, adds the bulleyaconitine A of recipe quantity, treat that its dissolving back adds lactose, treat to add Pulvis Talci again after its dissolving, stir, promptly get principal cartridge clothing layer liquid.Under the lasting stirring of magnetic stirrer, in fluid bed, carry out coating operation, after coating is accomplished dry several minutes.
The bag sealing coat: with hydroxypropyl methylcellulose and Pulvis Talci, Polyethylene Glycol is dissolved in and makes the isolation coat liquid with buffer action in the suitable quantity of water; Under the lasting stirring of magnetic stirrer, in fluid bed, carry out coating operation, after coating is accomplished dry several minutes.
Enteric-coating layer: Eudragit L 30D-55 is dispersed in the suitable quantity of water,, stirs, make enteric coating liquid to wherein slowly adding the Pulvis Talci of homogenize and diethyl phthalate in water; The medicine carrying micropill for preparing is placed in the fluid bed, spray into Eudragit L 30D-55 enteric coating liquid continuously, limit spray coating solution, the limit blowing hot-air promptly obtains the bulleyaconitine A enteric coated micropill.
Bag protective layer: hydroxypropyl methylcellulose and Pulvis Talci, Polyethylene Glycol be dissolved in make coating solution in the suitable quantity of water; Under the lasting stirring of magnetic stirrer, in fluid bed, carry out coating operation, after coating is accomplished dry several minutes.
The preparation of bulleyaconitine A multiple-unit pellet tablet: the bulleyaconitine A enteric coated micropill that makes and microcrystalline Cellulose, sodium stearyl fumarate are pressed into tablet and promptly get.
In order further to investigate enteric effect of the present invention, be index with the release degree of aconitine, according to 2010 editions two XD drug release determination methods of Chinese Pharmacopoeia, second method, study as follows:
These article of getting are release medium with 0.1mol/L hydrochloric acid solution 750ml, and rotating speed is 100 rev/mins, operation in accordance with the law, and it is an amount of to get solution in the 120th minute, and filtered solution is as need testing solution; In above-mentioned acid solution, add 0.2mol/L sodium radio-phosphate,P-32 solution 250ml immediately, and regulate pH to 6.8 with 2mol/L hydrochloric acid or 2mol/L sodium hydroxide solution, remained in operation 45 minutes, it is an amount of to get solution, filters, and subsequent filtrate is as need testing solution.It is an amount of that other gets these article, grinds, and precision takes by weighing the fine powder that is equivalent to average loading amount, adds above-mentioned hydrochloric acid solution and phosphate buffer respectively, and is ultrasonic, makes the aconitine stripping, filters, and gets subsequent filtrate as reference substance solution.Press the quality standard operation, embodiment 1,4,5 surveys bulleyaconitine A, 3-acetylaconitines, embodiment 3 survey lappaconitine hydrobromide are surveyed in enforcement 2.Stripping result such as table 1 in hydrochloric acid solution and the phosphate buffer:
The release result of table 1 embodiment sample in hydrochloric acid solution and phosphate buffer
| Release conditions | Hydrochloric acid solution 120 minutes | Phosphate buffer 45 minutes |
| Embodiment 1 | 1.8％ | 92.3％ |
| Embodiment 2 | 0.5％ | 87.5％ |
| Embodiment 3 | 2.7％ | 93.6％ |
| Embodiment 4 | 3.6％ | 93.6％ |
| Embodiment 5 | 3.5％ | 89.5％ |
Each embodiment all has significant enteric characteristics in the table 1: in hydrochloric acid solution, the amount that discharged aconitine in 120 minutes is lower than standards of pharmacopoeia 10%; In phosphate buffer, discharged greater than 70% in 45 minutes.The enteric of multiple-unit enteric coated preparation that experiment showed, aconitine of the present invention is respond well.Do not discharge medicine under one's belt in it, thereby eliminated, avoided untoward reaction, also avoided the destruction degraded of gastric acid the aconitine composition to upper gastrointestinal stimulation.In intestinal, discharge and overcome prominent the releasing of aconitine and do not have the too high phenomenon of local drug concentration, receive food effect less, little the stimulation of intestinal with multiunit form.
Claims (6)
1. an aconitine enteric coated micropill is characterized in that, is made up of the coatings that celphere is outer with being wrapped in celphere;
Described coatings comprises the principal agent layer that contains principal agent and adjuvant, is wrapped in the outer sealing coat of principal agent layer and is wrapped in the outer enteric layer of sealing coat; Described celphere is sucrose ball, starch ball or microcrystalline Cellulose ball;
The composition and the percentage by weight of said drug-loaded layer comprise:
Principal agent 0.1%～40%
Water-solubility carrier 4%～80%
Diluent 0%～50%
Antiplastering aid 0～30%
Described principal agent is bulleyaconitine A, 3-acetylaconitine and lappaconitine hydrobromide;
Described water-solubility carrier is selected from hydroxypropyl methylcellulose, polyvinylpyrrolidone, poloxamer or Polyethylene Glycol;
Described diluent is selected from a kind of in mannitol, dextran, lactose or the sucrose or more than one;
Described antiplastering aid is selected from Pulvis Talci, micropowder silica gel or magnesium stearate;
The component and the weight percent content of described sealing coat comprise:
Water-soluable gel material 10～90%
Plasticizer 0～20%
Defoamer 0～15%
Antiplastering aid 0～50%
Opacifier 0～10%
Described water-soluable gel material is hydroxypropyl methylcellulose or polyvinylpyrrolidone or both mixture.
Described plasticizer is selected from but is not limited to triethyl citrate, ATEC, tributyl 2-acetylcitrate, dibutyl sebacate, Dibutyl phthalate, glycerol, triacetin, monoacetin, cochin oil, Polyethylene Glycol, propylene glycol, diethyl phthalate, Tween-80, Semen Ricini wet goods, can be above-mentioned one or more combination.
Described defoamer is a dimethicone.
Described opacifier is medicinal pigments such as titanium dioxide, iron oxide red, iron oxide yellow.
2. aconitine enteric coated micropill according to claim 1 is characterized in that, the component and the percentage by weight of described enteric layer comprise:
Enteric layer coating material 20～100%
Plasticizer 0～20%
Defoamer 0～25%
Antiplastering aid 0～50%
Opacifier 0～10%
Described enteric solubility material coating material is selected from but is not limited to crylic acid resin, p-phthalic acid hydroxypropyl emthylcellulose and Cellacefate, SA-M, enteric Opadry; Eudragit E 30D-55; Eudragit RL 30D etc. can be above-mentioned one or more combination.
3. according to the enteric coated micropill of each described aconitine of claim 1～2, it is characterized in that the diameter of described micropill is 0.5～1.5mm, the diameter of celphere is 0.2～0.8mm.
4. one kind is equipped with the capsule of each described micropill of claim 1～3 or the tablet that is pressed into suitable adjuvant.
5. each the method for micropill of preparation claim 1～3 is characterized in that, comprises the steps:
(1) principal agent, water-solubility carrier, diluent, antiplastering aid are dissolved in the ethanol water, are wrapped in then on the celphere, obtain to have the medicine-feeding micropill of principal agent layer,
(2) will be wrapping to by the sealing coat coating solution that water-soluable gel material, plasticizer, defoamer, antiplastering aid and opacifier are formed with ethanol water on the medicine carrying micropill;
(3) the above-mentioned medicine carrying micropill that contains sealing coat is superscribed the enteric layer that one deck is made up of enteric material, plasticizer, defoamer, antiplastering aid, opacifier and ethanol water and promptly obtain the aconitine enteric coated micropill.
6. method according to claim 5 is characterized in that principal agent layer weightening finish layer is 2%～20%, and the sealing coat weightening finish is 1%～10%.
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| CN201010605213.9A CN102526233B (en) | 2010-12-24 | 2010-12-24 | A kind of multiple-unit enteric coated preparation containing aconitine and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102824317A (en) * | 2012-09-27 | 2012-12-19 | 云南昊邦制药有限公司 | New formulation containing bulleyaconitine A |
| CN103961336A (en) * | 2014-05-23 | 2014-08-06 | 黄永贤 | Aceclofenac enteric-coated pellet capsule and preparation method thereof |
| CN108294317A (en) * | 2018-01-31 | 2018-07-20 | 无限极（中国）有限公司 | A kind of walnut peptide enteric-coated micro-pill and preparation method thereof |
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| CN1903181A (en) * | 2006-08-08 | 2007-01-31 | 云南昊邦制药有限公司 | Enteric quick-dissolving tablets contg. aconitine, and its prepn. method |
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| CN1903181A (en) * | 2006-08-08 | 2007-01-31 | 云南昊邦制药有限公司 | Enteric quick-dissolving tablets contg. aconitine, and its prepn. method |
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| 殷栋二等: "地红霉素肠溶微丸的制备及处方优化", 《中国新药杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102824317A (en) * | 2012-09-27 | 2012-12-19 | 云南昊邦制药有限公司 | New formulation containing bulleyaconitine A |
| CN103961336A (en) * | 2014-05-23 | 2014-08-06 | 黄永贤 | Aceclofenac enteric-coated pellet capsule and preparation method thereof |
| CN108294317A (en) * | 2018-01-31 | 2018-07-20 | 无限极（中国）有限公司 | A kind of walnut peptide enteric-coated micro-pill and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102526233B (en) | 2016-01-27 |
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Address after: 214028 Changjiang South Road, new Wu District, Wuxi, Jiangsu Province, No. 12 Patentee after: Wuxi Jiyu Shanhe Pharmaceutical Co., Ltd Address before: 214028 No. 12 Changjiang South Road, New District, Jiangsu, Wuxi Patentee before: WUXI JIMIN KEXIN SHANHE PHARMACEUTICAL Co.,Ltd. |