CN100486566C - New type quick oral disintegration tablet of Subing and preparation method - Google Patents
New type quick oral disintegration tablet of Subing and preparation method Download PDFInfo
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- CN100486566C CN100486566C CNB2005100134952A CN200510013495A CN100486566C CN 100486566 C CN100486566 C CN 100486566C CN B2005100134952 A CNB2005100134952 A CN B2005100134952A CN 200510013495 A CN200510013495 A CN 200510013495A CN 100486566 C CN100486566 C CN 100486566C
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Abstract
An oral disintegrating tablet is prepared from storax, borneol, filler, disintegrant, flavouring, lubricant and flowing aid. Its preparing process is also disclosed. Its disintegrating time is 10-50 S.
Description
Technical field
The invention belongs to the novel form and the preparation of traditional corresponding Chinese patent medicine pill; Relate to and utilize Su Bing oral cavity disintegration tablet that modern solid dispersion technology provides and the drug effect stable content; Being particularly related to medicinal ingredient is the oral cavity quick disintegrating slice and the technology of preparing of Styrax, Borneolum Syntheticum solid dispersion medicine carrying microcapsule and microgranule.
Background technology
Effects such as Styrax Pilulae is a kind of Chinese patent medicine of classics, and it has causing resuscitation with aromatic drugs, regulating QI to relieve pain, resist myocardial ischemia and tangible thrombus effect, be used for coronary heart disease, uncomfortable in chest, feel suffocated, treatment of conditions such as precordialgia, cerebral thrombosis, cerebral infarction.But this traditional pill medication dose is big, slow curative effect, carry shortcoming such as inconvenience, takes inconvenience for the stupor critically ill patient especially.
Though commercially available Subing drop pills has improvement on dosage form, contained volatile ingredient storage period instability, content is difficult to control, and the onset of comparing with oral cavity disintegration tablet is slow, affects the treatment.Its reason is part volatile ingredient and the Borneolum Syntheticum in the main component styrax of this medicine, and easily distillation institute extremely.Borneolum Syntheticum as the medicine of having one's ideas straightened out, plays the effect of " fragrance is walked to scurry, and priming is up " in the cardiovascular medicament preparation in homeland pharmacy, be to alleviate one of main component uncomfortable in chest.Because this medicine exists the physical property of easy distillation, cause it to have many difficult problems all the time in the routine production of China's Chinese formulated products with in storing: as because the distillation of Borneolum Syntheticum have to high limit feed intake it for the content that guarantees it in production technology, not only waste herb resource but also make production environment abominable, the workman is difficult to stand; Because the Borneolum Syntheticum distillation causes effective content constantly to run off in patent medicine, unstable before the deadline with content to messenger drug, the quality of the pharmaceutical preparations is difficult to control; Bright through the accelerated test and the sight verification that keeps sample, some contains the Chinese patent medicine of Styrax, Borneolum Syntheticum, and annual before the deadline volatilization class composition distillation number of dropouts can be one of technical barrier of the current obstacle modernization of Chinese medicine up to about 30% unexpectedly; Because the content instability can't be stablized the medicinal content of control, the obstacle outlet so can not formulate content standard has limited it and has obtained the international market access smoothly; Because Borneolum Syntheticum distils and causes a lot of difficulties to the preparation packing that contains Borneolum Syntheticum, outward appearance, often pollute difficult problems such as the return of goods because of the Borneolum Syntheticum sublimate as the transparent plastic packaging of modern patent medicine " bubble eye " packing.
Oral cavity quick disintegrating slice (orally disiuteg rating tablet) is the novel form of developing in recent years.Compare with conventional tablet, this dosage form need not water and also need not to chew, and medicine places on the tongue, meets the rapid disintegrate of saliva meeting, borrows the swallowing act onset.Also can put the Sublingual, medicine passes through the mucosa absorption onset after the disintegrate rapidly.Current many Western medicine are made oral cavity quick disintegrating slice, and effect is fine, but Chinese medicine oral cavity quick disintegrating slice there be limited evidence currently of, and particularly the Chinese medicine to volatile, distillation and oiliness composition is difficult to tabletting.In existing production technology, because of Storax oil viscosity is big, mechanical tabletting resistance is big, and sticking to mould tool, tablet weight variation can not guarantee.Do not see the report of making quick oral disintegration tablet of Subing on the market as yet.
Above problem needs to be resolved hurrily.The novel form of developing this medicine is imperative.
Present disclosed relevant tablet, its medicinal ingredient all do not adopt the form of being used as medicine of solid dispersion such as microcapsule, microgranule, solve the technical problem of distillation medicine stability.
In sum, adopting modern medicinal agents technology and novel medicinal auxiliary material, seek to be suitable for parcel drug delivery technologies volatile, the distillation medicine, is the key of the modernization of Chinese medicine; The preparation new type quick oral disintegration tablet of Subing is the task of top priority of the modernization of Chinese medicine.
Summary of the invention
The problem that solves: at above-mentioned situation, in order to solve volatilization class, the easy Chinese medicine content of drug instability that distils, tablet preparation processing difficulties and traditional pill are taken the problem of inconvenience to stupor, critically ill patient.Provide a kind of application modernization parcel drug delivery technologies to prepare oral cavity quick disintegrating slice and method, thereby increased novel form and new production process for this medicine.
Technical scheme:
New type quick oral disintegration tablet of Subing, medicinal ingredient are Chinese medicine Styrax and Borneolum Syntheticum, and its pharmaceutical dosage is by ministry standard W S
3The taking dose of-B-2899-98 regulation, the mass percent of two flavor Chinese medicines is a Styrax 40%～60%, Borneolum Syntheticum is 60%～40%, and the form of being used as medicine of medicinal ingredient is to make solid dispersion medicine carrying microcapsule, microsphere and the microgranule that particle diameter is 1～100um with the modern pharmaceutical technology.Quick oral disintegration tablet of Subing is made up of with correctives, filler, disintegrating agent, lubricant and the fluidizer adjuvant interworking of crossing 80 mesh sieves the medicinal ingredient solid dispersion again.
Each component prescription is by weight percentage:
Medicinal ingredient solid dispersion 10.0～35.0%;
Filler 49.7～73.7%;
Disintegrating agent 10.0～11.0%;
Correctives 0.5～1.1%;
Lubricant 0.9～2.1%;
Fluidizer 0.9～2.1%;
Above-mentioned each composition sum is 100%.
The form of being used as medicine of medicinal ingredient Styrax can be medicine carrying microcapsule, the microsphere of this stearopten medical material of parcel, and the drug loading mass percent of its medicine carrying microcapsule, microsphere is 60%～90%.The form of being used as medicine of Borneolum Syntheticum can be the solid dispersion microgranule of Borneolum Syntheticum, and the drug loading mass percent of solid dispersion microgranule is 50～30%.
Need to prove:
Filler is selected from one or both in microcrystalline Cellulose, dextrin, lactose, starch or the mannitol.Disintegrating agent is selected from one or both in low substituent group hydroxypropyl methylcellulose (L-HPC), crospolyvinylpyrrolidone (PVPP), crosslinked carboxymethyl fecula sodium (CCMS-Na) or the cross-linking sodium carboxymethyl cellulose (CMC-Na).Correctives is selected from one or both in Mentholum, Oleum menthae, stevioside or the aspartame.Lubricant is selected from one or both in magnesium stearate, Stepanol MG, the Pulvis Talci.Fluidizer is selected from one or both in micropowder silica gel, the Pulvis Talci.
The preparation method of new type quick oral disintegration tablet of Subing, medicinal ingredient are Styrax and Borneolum Syntheticum, and its pharmaceutical dosage is by ministry standard WS
3The common dose of-B-2899-98 regulation, two flavor Chinese medicine quality percentage ratios are Styrax 40%～60%, Borneolum Syntheticum is 60%～40%.The form of being used as medicine of new type quick oral disintegration tablet of Subing medicinal ingredient is to form with solid dispersion and correctives, filler, disintegrating agent, lubricant and fluidizer adjuvant that the modern pharmaceutical technology is made.Solid dispersion is solid dispersion medicine carrying microcapsule, microsphere and microgranule.
Each component prescription of quick oral disintegration tablet of Subing is by weight percentage:
Medicinal ingredient solid dispersion 10.0～35.0%;
Filler 49.7～73.7%;
Disintegrating agent 10.0～11.0%;
Correctives 0.5～1.1%;
Lubricant 0.9～2.1%;
Fluidizer 0.9～2.1%;
Above-mentioned each composition sum is 100%.
Wherein, filler is selected from one or both in microcrystalline Cellulose, dextrin, lactose, starch or the mannitol.Disintegrating agent is selected from one or both in low substituent group hydroxypropyl methylcellulose (L-HPC), crospolyvinylpyrrolidone (PVPP), crosslinked carboxymethyl fecula sodium (CCMS-Na) or the cross-linking sodium carboxymethyl cellulose (CMC-Na), and correctives is selected from one or both in Mentholum, Oleum menthae, stevioside or the aspartame.Lubricant is selected from one or both in magnesium stearate, Stepanol MG, the Pulvis Talci, and fluidizer is selected from one or both in micropowder silica gel, the Pulvis Talci.
The concrete steps of quick oral disintegration tablet of Subing preparation are as follows:
(1) medicinal ingredient and processing
Medicinal ingredient: Styrax and Borneolum Syntheticum;
The processing of medicinal ingredient:
At first, above-mentioned volatilization class medical material is all given processing by the conventional method of pharmacopeia regulation;
Then, effective medicinal components is made solid dispersion medicine carrying microcapsule, microsphere and microgranule.
(2) film-making
Take by weighing medicinal ingredient respectively and pulverized and crossed the correctives of 80 mesh sieves by above-mentioned formula ratio, mix homogeneously, in addition filler, disintegrating agent, fluidizer, lubricant are also crossed 80 mesh sieves respectively, press the formula ratio mix homogeneously, all mix, cross 80 mesh sieves, tabletting again with the ingredient that is mixed with correctives; Tabletting adopts conventional tablet pharmaceutical equipment and pressing process or lyophilization, can make quick oral disintegration tablet of Subing.
The preparation of above-mentioned medicinal ingredient solid dispersion medicine carrying microcapsule, microsphere or microgranule is selected from following a kind of method:
Adopt the preparation of fusion method or solvent method:
With medicinal ingredient and carrier fusion or dissolving, solvent uses the organic solvent that can be used for pharmacy in the pharmacopeia regulation, and messenger drug fully stirs with composition and carrier mixing, be cooled to rapidly solid or except that desolvate solid dispersion, particle diameter is 1～100um.Wherein, the solid dispersion carrier is selected from Polyethylene Glycol, (being PEG-6000 or PEG-4000 or PEG-10000) polyvinylpyrrolidone (be PVP-K
15Or PVP-K
30Or PVP-K
60Or PVP-K
90) and beta-schardinger dextrin-and derivant thereof in one or both.
Or adopt parcel medicine carrying microcapsule or microsphere method to prepare:
Promptly with coacervation or interfacial polymerization, medicinal ingredient and capsule material are dissolved in the pharmacopeia regulation, can be used in the organic solvent of pharmacy, form organic facies.Water intaking in addition, the surfactant that adds water yield mass percent 2～4% disperses, and forms water.Water is stirred or ultrasound condition under, organic facies is at the uniform velocity splashed into aqueous phase, it is fully disperseed, regulate pH value to 4～10, through plasticising, crosslinked and solidify, obtain medicinal parcel medicine carrying microcapsule or microsphere; Doubly water extraction organic solvent of reuse 10-15, after filtration, drying, obtain discharging medicinal ingredient, runny parcel medicine carrying microcapsule or microsphere.Above-mentioned stirring or ultrasonic time are 0.5～2 hour; Crosslinked when stirring, curing, be not less than 2 hours crosslinked and hardening time;
The Chinese medicine Styrax is handled through said method, promptly obtains the drug loading mass percent and be 60%～90% solid Styrax microcapsule or microsphere, and its particle diameter is 1～100um.
The Chinese medicine Borneolum Syntheticum is handled through said method, promptly obtains the drug loading mass percent and be 50～30% Borneolum Syntheticum solid dispersion microgranule, and its particle diameter is 1～100um.
In preparation parcel medicine carrying microcapsule process, capsule material amount percent concentration is 10～30% in the organic facies, and water is 20～50:1 with the ratio of organic facies volume.
Wherein, the capsule material is selected from natural and the synthetic high polymer pharmaceutic adjuvant.Natural polymer medical adjuvant is gelatin, arabic gum, sodium alginate, cellulose and cellulosic derivant, chitosan and derivant 1-3 kind thereof; The synthetic high polymer pharmaceutic adjuvant is the copolymer of poly-methyl-prop diluted acid, polymethyl acrylate, poly-methyl-prop diluted acid and poly-methyl-prop diluted acid ester, Youteqi E-100, Youteqi EPO, polyvinyl alcohol, the 1-3 kind in polyvinylpyrrolidone and the Polyethylene Glycol.Organic solvent is selected from organic solvent ethanol, ethyl acetate, Ethyl formate or the chloroform that approval is used in the pharmacopeia.Surfactant is selected from tween, class of department, sodium lauryl sulphate, polyvinyl alcohol, polyvinylpyrrolidone or Polyethylene Glycol.Plasticizer is selected from citric acid, triethyl citrate, Polyethylene Glycol or calcium chloride.Cross-linking agent is selected from formaldehyde or glutaraldehyde.
The experiment that new type Subing oral cavity disintegration tablet Chinese People's Anti-Japanese Military and Political College Mus experimental thrombosis forms:
Table 1 new type Subing mouth collapse to rat moving-the thrombotic inhibitory action of vein bypass (X ± s, n=10)
Compare with matched group,
*P＜0.05,
*P＜0.01
Table 2 new type Subing oral cavity disintegration tablet to the influence of external thrombolytic (X ± s, n=10)
Compare with matched group,
*P＜0.05
*P＜0.01
* *P＜0.001
Annotate: the new type Subing oral cavity disintegration tablet has the obvious suppression effect to thrombosis as can be seen from the above table.
Beneficial effect:
The invention provides a kind of drug effect stable content, taking convenience, to indication rapid-action quick oral disintegration tablet of Subing and technology of preparing.Styrax, Borneolum Syntheticum are to alleviate uncomfortable in chest, two kinds of main components of thrombus outstanding effect, and the present invention has overcome their volatile, distillation, makes its products obtained therefrom and production technology bring inconvenience.Owing to use modern solid dispersion technology, volatilization class Chinese medicine is dispersed on the solid dispersion soluble in water, make the solid dispersion that particle diameter is 1～100um, as parcel medicine carrying microcapsule, microsphere or disperse particles.This medicine carrying microcapsule (ball) drug loading height, and limited the distillation and the loss of its effective ingredient.Like this, not only stablized the effective content of volatilization class Chinese medicine, and improved this water-fast medicine of Borneolum Syntheticum and in water, dissolve and dispersibility.This oral cavity quick disintegrating slice is at the lay up period of medicine, the loss that can not distil of the class of wherein volatilizing Chinese medicine, effective ingredient has rhythm and pace of moving things ground to discharge, guaranteed pharmaceutical effectiveness and storage period content stable.Synergism by parcel medicine carrying dispersion technology and disintegrating agent, make drug oral after, can be not moisture in the oral cavity, just fully disintegrate.The preparation disintegration time can be finished in 10～50 seconds, and do not have sand type, have no side effect, avirulence, be the old man or swallowed the ideal administering mode of impaired patients.It can promptly alleviate uncomfortable in chest, distressed, is convenient to coronary heart disease patient's first aid and prevention, takes inconvenience, the slow problem of onset thereby solved stupor, critically ill patient.In addition, utilize carrier can also cover the bad smell of medicine, for the cardiovascular and cerebrovascular diseases medicine has increased very practical novel form.Preparation method of the present invention, to have solved Storax oil viscosity big, sticking to mould tool, the unwarrantable disadvantage of tablet weight variation, and use conventional tablet pharmaceutical equipment, i.e. directly compressible production.This product has been owing to controlled the easily problem of distillation of Borneolum Syntheticum, effect duration content of drug controlled, solved the restive key problem in technology of Chinese medicine content of drug.The present invention has not only improved drug quality, has also optimized production environment, has both had an economic benefit, and social benefit is arranged again.
Description of drawings:
Fig. 1: the content/time relationship comparison diagram of new type Subing oral cavity disintegration tablet and Styrax, Borneolum Syntheticum traditional method compressed tablet.
Below in conjunction with specific embodiment, the present invention will be further described.Its specific embodiments only should be understood to illustrating, but not any way limits the scope of the invention.
Embodiment 1:
The selection of medicinal ingredient and processing
Medicinal ingredient: Styrax and Borneolum Syntheticum.
The processing of medicinal ingredient:
At first, above-mentioned volatilization class medical material is all given processing by the conventional method of pharmacopeia regulation;
Then, effective medicinal components is made solid dispersion, its method is:
Get Styrax volatile oil 10g, join among the alcoholic solution 50ml that contains the strange E-100 of 6% You Te, make organic facies.Other 1000ml that fetches water adds Polyethylene Glycol 30g and disperses, and forms water; Water is being carried out under the stirring condition organic facies is at the uniform velocity splashed into aqueous phase, crosslinked when stirring, curing, the time is 2 hours, obtains medicinal Styrax parcel medicine carrying microcapsule; Reuse water 15 ascending are got organic solvent, more after filtration, drying, obtain discharging medicinal ingredient, runny parcel Styrax medicine carrying microcapsule.Drug loading is 80% solid Styrax microcapsule or microsphere, and its particle diameter is 1～100um.
Get Borneolum Syntheticum 10g, be dissolved in the 50ml ethanol, add polyvinylpyrrolidone and each 6g of ethyl cellulose, form oil phase, other 1000ml that fetches water adds 30g sodium lauryl sulphate and 0.5g Polyethylene Glycol, disperses the formation water; Water is being carried out under the stirring condition organic facies is at the uniform velocity splashed into aqueous phase, crosslinked when stirring, solidified 2 hours, obtain medicinal Borneolum Syntheticum parcel medicine carrying microcapsule; Extract organic solvent with 15 premium on currency, more after filtration, drying, obtain to discharge medicinal ingredient, runny parcel Borneolum Syntheticum medicine carrying microcapsule.
The Chinese medicine Borneolum Syntheticum is handled through said method, promptly obtains drug loading and be 30% Borneolum Syntheticum medicine carrying microcapsule, and its particle diameter is 1～100um.
The pressing port disintegrating tablet
Its prescription is:
Medicinal ingredient medicine carrying Styrax 4.40g
Medicine carrying Borneolum Syntheticum 5.60g
Microcrystalline Cellulose 14.6g
Mannitol 22g
Cross-linking sodium carboxymethyl cellulose 12.00g
Aspartame 0.15g
Herba Menthae 0.15g
Magnesium stearate 0.55g
Micropowder silica gel 0.55g
Make 1000 altogether
Concrete preparation method is:
By above-mentioned recipe quantity medicinal ingredient Styrax and the Borneolum Syntheticum for preparing wrapped up medicine carrying microcapsule and aspartame, the Herba Menthae mix homogeneously pulverized through 80 mesh sieves, took by weighing cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, mannitol, micropowder silica gel, the magnesium stearate of 80 mesh sieves more respectively by recipe quantity, mix homogeneously.Use conventional tablet pharmaceutical equipment and pressing process tabletting, can make oral cavity quick disintegrating slice.This oral cavity disintegration tablet disintegration in 37 ℃ of aqueous mediums is 20～30 seconds.
Fig. 1 is new type quick oral disintegration tablet of Subing of the present invention and traditional Su Bing compressed tablet content/time relationship comparison diagram.Wherein 1 is new type quick oral disintegration tablet of Subing content/time history of the present invention, and 2 is tradition Soviet Union content of bornyl alcohol/time history.As seen from Figure 1, the new type Subing oral cavity disintegration tablet has the characteristics of stable content.
Embodiment 2:
Getting the 30g sodium alginate joins in the 100ml water, adding Styrax volatile oil 10g again stirs, it being added drop-wise in the chitosan glacial acetic acid solution of calcium chloride (this liquid method for making: water intaking 1000ml adds glacial acetic acid, 5g chitosan and the 15g calcium chloride of 20ml) stirs and promptly obtained Styrax parcel medicine carrying microcapsule in 1 hour.Again after filtration, drying, obtain discharging medicinal ingredient, runny parcel Styrax medicine carrying microcapsule.
Film-making prescription (by weight) component is:
Medicinal ingredient medicine carrying Styrax 4.40g
Medicine carrying Borneolum Syntheticum 5.60g
Microcrystalline Cellulose 19.0g
Mannitol 14.4g
Carboxymethyl starch sodium 15.0g
Herba Menthae 0.25g
Stevioside 0.05g
Magnesium stearate 0.65g
Micropowder silica gel 0.65g
Make 1000 altogether
Film-making: concrete preparation method is:
By above-mentioned recipe quantity with stevioside, Herba Menthae powder pulverize separately cross 80 mesh sieves, with medicine carrying Styrax, Borneolum Syntheticum, mix homogeneously.In addition will cross carboxymethyl starch sodium, microcrystalline Cellulose, mannitol, micropowder silica gel, the magnesium stearate mix homogeneously of 80 mesh sieves respectively by recipe quantity, again be mixed with that stevioside mixes with the medicinal ingredient of Herba Menthae, tabletting, make oral cavity disintegration tablet.This oral cavity disintegration tablet disintegration in 37 ℃ of water is 20～30 seconds.
Other is with embodiment 1.
Embodiment 3:
The selection of medicinal ingredient and processing and with embodiment 1.
Prescription (by weight) component is:
Medicinal ingredient medicine carrying Styrax 4.40g
Medicine carrying Borneolum Syntheticum 5.60g
Microcrystalline Cellulose 21.00g
Mannitol 15.60g
Crospolyvinylpyrrolidone 12.00g
Stevioside 0.05g
Herba Menthae 0.25g
Magnesium stearate 0.55g
Micropowder silica gel 0.55g
Make 1000 altogether
Concrete preparation method is:
To pulverize the stevioside of 80 mesh sieves and medicine carrying Styrax, Borneolum Syntheticum by the recipe quantity mix homogeneously, in addition with cross-linked pvp, microcrystalline Cellulose, mannitol, micropowder silica gel, magnesium stearate are crossed 80 mesh sieves respectively and are pressed the recipe quantity mix homogeneously, with the medicinal ingredient mix homogeneously that is mixed with stevioside, tabletting promptly gets oral cavity disintegration tablet again.This oral cavity disintegration tablet disintegration in 37 ℃ of aqueous mediums is 40～50 seconds.
Embodiment 4:
The selection of medicinal ingredient and pretreatment:
Get Styrax volatile oil 10g, join among the aqueous solution 40ml that contains 4% gelatin and 4% arabic gum, add the fine little element of 1g ethoxy again, stirring fully mixes it, forms organic facies.Other 2000ml that fetches water adds the 30g Polyethylene Glycol, disperses, and forms water; Under to water stirring or ultrasound condition, organic facies at the uniform velocity is added drop-wise to aqueous phase, add 20% formaldehyde or 50% glutaraldehyde 5ml again, the control pH value is 8～9, stirs 0.8 hour, crosslinked when stirring, curing
2Hour obtain medicinal Styrax parcel medicine carrying microcapsule; Again after filtration, drying, obtain discharging medicinal ingredient, runny parcel Styrax medicine carrying microcapsule.
Get Borneolum Syntheticum 10g, be dissolved in the 50ml ethanol, add 3g polyvinylpyrrolidone and 1g ethyl cellulose, form oil phase, other 1000ml that fetches water adds the sodium lauryl sulphate and the Polyethylene Glycol of 10g of 10g, disperses the formation water; Water is being carried out under the stirring condition organic facies is at the uniform velocity splashed into aqueous phase, crosslinked when stirring, curing obtained medicinal Borneolum Syntheticum parcel medicine carrying microcapsule in 2 hours through crosslinked, curing; Reuse 20 premium on currency extract organic solvent, more after filtration, drying, obtain discharging medicinal ingredient, runny parcel Borneolum Syntheticum medicine carrying microcapsule.
Film-making: prescription (by weight) component is:
Medicinal ingredient medicine carrying Styrax 4.40g
Medicine carrying Borneolum Syntheticum 5.60g
Lactose 10.7g
Starch 24.2g
Crospolyvinylpyrrolidone 13.7g
Aspartame 0.15g
Herba Menthae 0.15g
Stepanol MG 0.55g
Micropowder silica gel 0.55g
Make 1000 altogether
Concrete preparation method is:
To give aspartame, the Herba Menthae that first medicine carrying Styrax for preparing and Borneolum Syntheticum medicinal ingredient and pulverize separately are crossed 80 mesh sieves, mix homogeneously by recipe quantity; Took by weighing crospolyvinylpyrrolidone, lactose, starch, micropowder silica gel, the Stepanol MG mix homogeneously of 80 mesh sieves more respectively by recipe quantity, mix with the medicinal ingredient that is mixed with correctives aspartame, Herba Menthae again, use conventional tablet pharmaceutical equipment and pressing process tabletting, can make oral cavity disintegration tablet.This oral cavity disintegration tablet is in 37 ℃ of aqueous mediums, and be 20～30 seconds disintegration.Other is with embodiment 1.
Embodiment 5:
Film-making prescription (by weight) component is:
Medicinal ingredient medicine carrying Styrax 6g
Medicine carrying Borneolum Syntheticum 4g
Dextrin 20g
Lactose 13.4g
Carboxymethyl starch sodium 15.0g
Herba Menthae 0.25g
Stevioside 0.05g
Magnesium stearate 0.65g
Micropowder silica gel 0.65g
Make 1000 altogether
To give medicine carrying Styrax and Borneolum Syntheticum medicinal ingredient for preparing earlier and the stevioside of pulverizing 80 mesh sieves, Herba Menthae by the recipe quantity mix homogeneously; With the carboxymethyl starch sodium, lactose, dextrin, micropowder silica gel, the magnesium stearate that took by weighing 80 mesh sieves by recipe quantity, mix homogeneously uses conventional tablet pharmaceutical equipment and pressing process tabletting, can make oral cavity disintegration tablet again.This sheet disintegration in 37 ℃ of aqueous mediums is 30～40 seconds.Other is with embodiment 1.
Embodiment 6:
Its film-making prescription (by weight) component is:
Medicinal ingredient medicine carrying Styrax 4.4g
Borneolum Syntheticum 5.6g
Microcrystalline Cellulose 21g
Mannitol 15g
Crospolyvinylpyrrolidone 11.4g
Stevioside 0.15g
Herba Menthae 0.25g
Magnesium stearate 1.1g
Pulvis Talci 1.1g
Make 1000 altogether
To give stevioside, the Herba Menthae that first medicine carrying Styrax for preparing and Borneolum Syntheticum medicinal ingredient and pulverize separately are crossed 80 mesh sieves, mix homogeneously by recipe quantity; With the crospolyvinylpyrrolidone, microcrystalline Cellulose, mannitol, Pulvis Talci and the magnesium stearate that took by weighing 80 mesh sieves by recipe quantity, mix homogeneously uses conventional tablet pharmaceutical equipment and pressing process tabletting, can make oral cavity quick disintegrating slice again.This sheet disintegration in 37 ℃ of aqueous mediums is 30～40 seconds.Other is with embodiment 1.
Embodiment 7:
To give stevioside, the Herba Menthae that first medicine carrying Styrax for preparing and Borneolum Syntheticum medicinal ingredient and pulverize separately are crossed 80 mesh sieves, mix homogeneously by recipe quantity; With the amylopectin, crospolyvinylpyrrolidone, the mix homogeneously that took by weighing 80 mesh sieves by recipe quantity, use freeze drying equipment to prepare the lyophilization sheet again, can make oral cavity quick disintegrating slice.This sheet disintegration in 37 ℃ of aqueous mediums is 10～30 seconds.
Medicinal ingredient medicine carrying Styrax 4.40g
Medicine carrying Borneolum Syntheticum 5.60g
Amylopectin 15.7g
Mannitol 22g
Cross-linking sodium carboxymethyl cellulose 12.00g
Aspartame 0.15g
Herba Menthae 0.15g
Make 1000 altogether.Other is with embodiment 1.
Embodiment 8:
Get Borneolum Syntheticum 10g, with the fusion of 30g polyethylene glycol 6000 carrier, make medicine and carrier mixing, fully stir, be cooled to solid rapidly and get solid dispersion, other is with embodiment 1.
Claims (6)
1. quick oral disintegration tablet of Subing, medicinal ingredient is Chinese medicine Styrax and Borneolum Syntheticum, its pharmaceutical dosage is by ministry standard WS
3The taking dose of-B-2899-98 regulation, the mass percent of two flavor Chinese medicines is a Styrax 40%～60%, Borneolum Syntheticum is 60%～40%, the form of being used as medicine that it is characterized in that medicinal ingredient is that particle diameter is solid dispersion medicine carrying microcapsule, microsphere and the microgranule of 1～100um, quick oral disintegration tablet of Subing is made up of with correctives, filler, disintegrating agent, lubricant and the fluidizer adjuvant interworking of crossing 80 mesh sieves the medicinal ingredient solid dispersion again, and each component prescription is by weight percentage:
Medicinal ingredient solid dispersion 10.0～35.0%;
Filler 49.7～73.7%;
Disintegrating agent 10.0～11.0%;
Correctives 0.5～1.1%;
Lubricant 0.9～2.1%;
Fluidizer 0.9～2.1%;
Above-mentioned each composition sum is 100%,
Wherein the form of being used as medicine of medicinal ingredient Styrax is medicine carrying microcapsule, the microsphere of this stearopten medical material of parcel, and its drug loading mass percent is 60%～90%; The form of being used as medicine of Borneolum Syntheticum is the solid dispersion microgranule of Borneolum Syntheticum, and its drug loading mass percent is 50～30%;
The preparation method of medicinal ingredient solid dispersion medicine carrying microcapsule, microsphere or microgranule:
Adopt fusion method to prepare Borneolum Syntheticum solid dispersion microgranule: with medicinal ingredient and carrier fusion, messenger drug fully stirs with composition and carrier mixing, is cooled to solid rapidly and gets the solid dispersion microgranule, and particle diameter is 1～100um; Carrier is selected from Polyethylene Glycol;
Styrax adopts parcel medicine carrying microcapsule or the preparation of microsphere method: promptly with coacervation or interfacial polymerization, medicinal ingredient and capsule material are dissolved in pharmacopeia organic solvent regulation, that can be used for pharmacy, form organic facies; Water intaking in addition, the surfactant that adds water yield mass percent 2～4% disperses, and forms water; Water is stirred or ultrasound condition under, organic facies is at the uniform velocity splashed into aqueous phase, it is fully disperseed, regulate pH value to 4～10, through plasticising, crosslinked and solidify, obtain medicinal parcel medicine carrying microcapsule or microsphere; Doubly water extraction organic solvent of reuse 10-15, after filtration, drying, obtain discharging medicinal ingredient, runny parcel medicine carrying microcapsule or microsphere; Above-mentioned stirring or ultrasonic time are 0.5～2 hour; Crosslinked when stirring, curing, be not less than 2 hours crosslinked and hardening time;
The capsule material is selected from natural and the synthetic high polymer pharmaceutic adjuvant, and natural polymer medical adjuvant is gelatin, arabic gum, sodium alginate, cellulose, chitosan 1-3 kind; The synthetic high polymer pharmaceutic adjuvant is copolymer Youteqi E-100, Youteqi EPO, the polyvinyl alcohol of poly-methyl-prop diluted acid and poly-methyl-prop diluted acid ester, the 1-3 kind in polyvinylpyrrolidone and the Polyethylene Glycol.
2. according to the described quick oral disintegration tablet of Subing of claim 1, it is characterized in that filler is selected from one or both in microcrystalline Cellulose, dextrin, lactose, starch or the mannitol; Disintegrating agent is selected from one or both among low substituent group hydroxypropyl methylcellulose L-HPC, crospolyvinylpyrrolidone PVPP, crosslinked carboxymethyl fecula sodium CCMS-Na or the cross-linking sodium carboxymethyl cellulose CMC-Na; Correctives is selected from one or both in Mentholum, Oleum menthae, stevioside or the aspartame; Lubricant is selected from one or both in magnesium stearate, Stepanol MG, the Pulvis Talci; Fluidizer is selected from one or both in micropowder silica gel, the Pulvis Talci.
3. the preparation method of the described quick oral disintegration tablet of Subing of claim 1, medicinal ingredient is Styrax and Borneolum Syntheticum, its pharmaceutical dosage is by ministry standard WS
3The common dose of-B-2899-98 regulation, two flavor Chinese medicine quality percentage ratios are Styrax 40%～60%, Borneolum Syntheticum is 60%～40%, the form of being used as medicine that it is characterized in that the new type quick oral disintegration tablet of Subing medicinal ingredient is to form with solid dispersion and correctives, filler, disintegrating agent, lubricant and fluidizer adjuvant, and solid dispersion is solid dispersion medicine carrying microcapsule, microsphere and microgranule;
Each component prescription of quick oral disintegration tablet of Subing is by weight percentage:
Medicinal ingredient solid dispersion 10.0～35.0%;
Filler 49.7～73.7%;
Disintegrating agent 10.0～11.0%;
Correctives 0.5～1.1%;
Lubricant 0.9～2.1%;
Fluidizer 0.9～2.1%;
Above-mentioned each composition sum is 100%,
The concrete steps of quick oral disintegration tablet of Subing preparation are as follows:
(1) medicinal ingredient and processing
Medicinal ingredient: Styrax and Borneolum Syntheticum;
The processing of medicinal ingredient:
At first, above-mentioned volatilization class medical material is all given processing by the conventional method of pharmacopeia regulation;
Then, effective medicinal components is made solid dispersion medicine carrying microcapsule, microsphere and microgranule;
Adopt fusion method to prepare Borneolum Syntheticum solid dispersion microgranule: with medicinal ingredient and carrier fusion, messenger drug fully stirs with composition and carrier mixing, is cooled to solid rapidly and gets the solid dispersion microgranule, and particle diameter is 1～100um; The Chinese medicine Borneolum Syntheticum is handled through said method, and promptly obtaining the drug loading mass percent is the Borneolum Syntheticum solid dispersion microgranule of 50-30%;
SUHE is fragrant adopts parcel medicine carrying microcapsule or the preparation of microsphere method: promptly with coacervation or interfacial polymerization, medicinal ingredient and capsule material are dissolved in the pharmacopeia regulation, can be used in the organic solvent of pharmacy the formation organic facies; Water intaking in addition, the surfactant that adds water yield mass percent 2～4% disperses, and forms water; Water is stirred or ultrasound condition under, organic facies is at the uniform velocity splashed into aqueous phase, it is fully disperseed, regulate pH value to 4～10, through plasticising, crosslinked and solidify, obtain medicinal parcel medicine carrying microcapsule or microsphere; Doubly water extraction organic solvent of reuse 10-15, after filtration, drying, obtain discharging medicinal ingredient, runny parcel medicine carrying microcapsule or microsphere; Above-mentioned stirring or ultrasonic time are 0.5～2 hour; Crosslinked when stirring, curing, be not less than 2 hours crosslinked and hardening time;
The Chinese medicine Styrax is handled through said method, promptly obtains the drug loading mass percent and be 60%～90% solid Styrax microcapsule or microsphere, and its particle diameter is 1～100um;
(2) film-making
Take by weighing medicinal ingredient respectively and pulverized and crossed the correctives of 80 mesh sieves by above-mentioned formula ratio, mix homogeneously, in addition filler, disintegrating agent, fluidizer, lubricant are also crossed 80 mesh sieves respectively, press the formula ratio mix homogeneously, all mix, cross 80 mesh sieves, tabletting again with the ingredient that is mixed with correctives; Tabletting adopts conventional tablet pharmaceutical equipment and pressing process or lyophilization, can make quick oral disintegration tablet of Subing.
4. according to the preparation method of the described quick oral disintegration tablet of Subing of claim 3, it is characterized in that filler is selected from one or both in microcrystalline Cellulose, dextrin, lactose, starch, amylopectin or the mannitol; Disintegrating agent is selected from one or both among crospolyvinylpyrrolidone PVPP, crosslinked carboxymethyl fecula sodium CCMS-Na or the cross-linking sodium carboxymethyl cellulose CMC-Na; Correctives is selected from one or both in Mentholum, Oleum menthae, stevioside or the aspartame; Lubricant is selected from one or both in magnesium stearate, Stepanol MG, the Pulvis Talci; Fluidizer is selected from one or both in micropowder silica gel, the Pulvis Talci.
5. according to the preparation method of the described quick oral disintegration tablet of Subing of claim 3, it is characterized in that capsule material amount percent concentration is 10～30% in the organic facies in preparation parcel medicine carrying microcapsule process, water is 20～50:1 with the ratio of organic facies volume.
6. according to the preparation method of the described quick oral disintegration tablet of Subing of claim 3, it is characterized in that the capsule material is selected from natural and the synthetic high polymer pharmaceutic adjuvant, natural polymer medical adjuvant is gelatin, arabic gum, sodium alginate, cellulose, chitosan 1-3 kind; The synthetic high polymer pharmaceutic adjuvant is the copolymer of poly-methyl-prop diluted acid and poly-methyl-prop diluted acid ester, Youteqi E-100, Youteqi EPO, polyvinyl alcohol, the 1-3 kind in polyvinylpyrrolidone and the Polyethylene Glycol; Organic solvent is selected from the organic solvent ethanol that approval is used in the pharmacopeia; Surfactant is selected from sodium lauryl sulphate, polyvinyl alcohol, polyvinylpyrrolidone or Polyethylene Glycol; Plasticizer is selected from glacial acetic acid, Polyethylene Glycol or calcium chloride; Cross-linking agent is selected from formaldehyde or glutaraldehyde.
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