CN101804038A - Huperzine A preparation for treating schizophrenia and nervous function damage and preparation method thereof - Google Patents
Huperzine A preparation for treating schizophrenia and nervous function damage and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a huperzine A preparation for treating schizophrenia and nervous function damage and a preparation method thereof. The preparation method comprises the following steps: using a solvent dispersing method and a solid-liquid phase dispersing and melting method to properly dissolve huperzine A by solvent, preparing stable huperzine A hydrochloride solution, spraying the huperzine A hydrochloride solution in an auxiliary material by dispersion, or preparing solid dispersoid mixture with uniform phase dispersion, crushing, mixing and stirring uniformly, directly adding a lubricating agent for tabletting, also being capable of adding a binding agent, granulating, drying, adding the lubricating agent, and tabletting. The phase-dispersing mixture of huperzine A also can be added with the lubricating agent with proper amount for mixing, and then filled into a capsule. The preparation is used for treating the symptoms of all the periods of schizophrenia, and has the advantages of having the effects of protecting oxidative stress toxicity of nerve cells generated by resisting Beta amyloid peptide and inducing cell apoptosis, promoting the growth of nerve growth factor, being effective for treating inflammation in cerebral hemorrhage and inflammation of cerebral ischemic injury, having long action time of drugs, being convenient to application of oral administration/containing administration and the like. The invention has high content of huperzine A preparation, stable preparation quality and good bioavailability and can improve the medication compliance of patients with schizophrenia and senile dementia.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to treat huperzine A preparation and manufacture method thereof that schizophrenia and nervous function damage are used.
Background technology
The chemistry of huperzine A is called (5R, 9R, 11E) 5-amino-11-ethylidene-5,6,9,10-tetrahydrochysene-7 methyl-5,9-methylene-5,9-cycloocta (b) pyridine-2 (1H) ketone.Huperzine A is that (Huperzia serrata (Thunb.) Trev (claim Herba Lycopodii serrati again from China's Chinese herbal medicine Huperziaceae plant Herba Lycopodii serrati, the feet added to a snake by an ignorant artist grass) the pure-natural biological alkali that extracts in the plant such as, often the Herba Lycopodii serrati herb is applied to traumatic injury in that China is among the people, congestion swells and ache, diseases such as schizophrenia, and the huperzine A that wherein contains is a kind of efficient, the maincenter acetylcholinesteraseinhibitors inhibitors of reversible and high selectivity, efficiently, low toxicity, true acetylcholine esterase had selective inhibitory, easily pass through blood brain barrier, long action time, has the promotion memory represents, the effect that hypermnesis keeps.The 1970's began China medicine worker and begin one's study the Huperziaceae plant to degree of inhibition of AchE, Zhejiang people's health experiment Ni of institute admired kind in 1979, Shen Wenzhao etc. utilize that feet added to a snake by an ignorant artist grass extract formulation-No. 3 sheets of feet added to a snake by an ignorant artist grass are applied to clinical, treatment schizophrenia, Toxicological Research institute of 1981-1982 Military Medical Science Institute, Zhejiang Province medical scientific institute, the scientist of the Shanghai medicine unit of grade of the Chinese Academy of Sciences is from Herba Lycopodii serrati, extracted huperzine A in the plants such as Phlegmariurus fordii (Bak) Ching-Bak, the bright grade of Tang Xi in 1986 huperzine A of reporting for work first has the effect that improves learning and memory in rats, Zhejiang medical courses in general institute had at first developed the huperzine A injection in 1984, and this achievement was won national invention second prize in 1987, whole nation invention fair gold medal, French eureka international fair gold medal in 1988.The domestic huperzine A tablet of at first researching and developing in 1985 is applied to treat diseases such as senile dementia, benign memory deficits.The clinician of China attempts Herba Lycopodii serrati and huperzine A preparation are applied to the schizophrenic for many years, and obtains effect preferably.The China and the U.S. show 2,3 clinical trial phases and the evaluation of huperzine A: compare with similar medicine; huperzine A has rapid-action; easily see through blood brain barrier; and the oxidative stress toxicity of neuroprotective cell antagonism beta-amyloyd peptide generation is arranged and bring out the apoptosis effect; promote the nerve growth factor growth; treatment to the inflammation of inflammation in the cerebral hemorrhage and cerebral ischemia is effective, and drug treating time is long, can make things convenient for advantages such as oral application.Existing market is sold and is mainly contained huperzine A tablet, capsule and injection, and contains the healthcare food preparation of huperzine A composition.Because huperzine A is water insoluble, have and draw moistly, and principal agent dosage is few when using, and uses the method preparation of progressively increasing of comminution by gas stream or equivalent when the huperzine A sheet of traditional method preparation and capsule.Existing huperzine A injection needs intramuscular injection to use, and patient uses inconvenience, and brings unnecessary misery, and when on probation for a long time, patient dependence is poor, and the high-load oral formulations efficient, that bioavailability is high of treatment schizophrenia aspect does not emerge as yet.Thereby the schizoid huperzine A preparation of exploitation treatment has wide practical value and social benefit.Than selling a 50ug/ sheet/capsule in the market, this a preparation 100ug or 200ug/ sheet/capsular high-load is more suitable for clinical needs, has greatly improved patient's compliance.The present invention is by solvent-applied dispersion method and solid, liquid dispersion method and huperzine A formed stable salify mode earlier mutually, be developed into the huperzine A preparation, correct and some defectives when overcoming traditional method and making huperzine A tablet, capsule, serial huperzine A volumes of formulation of the present invention is little, can oral and sublingual administration, also can need not water delivery service, good mouthfeel, great convenience is provided particularly for schizophrenic and elderly patients and bed patient, the huperzine A preparation of using the present invention's preparation has efficiently, the convenient and high characteristics of bioavailability.
Summary of the invention
The present invention is logical to be the solvent-applied dispersion method, and technology such as solid, liquid phase dispersion method and salify rapid release are made the huperzine A preparation, had fast evenly to discharge, and dissolution and dissolution rate are stable, the steady quality characteristics.Because huperzine A formulation content height of the present invention, volume are little, easy to carry and use, can oral and sublingual administration, and this type of preparation bioavailability height.Relatively with the common huperzine A tablet of manufacturing, capsule, huperzine A pharmaceutical adjunct of the present invention utilizes the phase process for dispersing, consumption is few, need not complicated, expensive device such as micronization, working condition equipment is simple, reduces and pollutes, and reduces labor intensity, reduce production costs, these have also shown characteristics of the present invention.The selected adjuvant of the present invention all meets the pharmaceutic adjuvant of medicinal requirements, by a series of tests and summary, optimizing this drug component composition comprises: huperzine A, appropriate amount of auxiliary materials and solvent, wherein adjuvant comprises the fillibility adjuvant and has the plasticity adjuvant, and the fillibility adjuvant has: polyethylene glycol 6000, Macrogol 4000, polyethylene glycol 1500, polyoxyethylene stearate (40) ester, hydroxypropyl emthylcellulose (HPMC), ethyl cellulose (HEC), HPMC (HPC-Na), polyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, polyoxyethylene sorbitan monoleate, citric acid, xylitol, sorbitol, mannitol, corn starch, dextrin, microcrystalline Cellulose, micropowder silica gel, magnesium stearate.The plasticity adjuvant has gelatin, arabic gum, alginic acid.And the sweet and essence of A Siba.
Best substrate adjuvant of the present invention is hydroxypropyl emthylcellulose (HPMC), ethyl cellulose (HEC), HPMC (HPC-Na), cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose and mannitol, starch.And the ratio of mannitol and the weight of starch is 1: 0.3-0.5.Xylitol is 1 with the ratio of the weight of starch: 0.3-1: 0.5, or the ratio of sorbitol and the weight of starch is 1: 0.2-1: 0.5, and microcrystalline Cellulose is 1 with the ratio of starch moral weight: 0.2-1: 0.5.Huperzine A is 1 with the ratio of the weight of adjuvant in the pharmaceutical composition of the present invention: 300-1: 1000.
Preferred pharmaceutical composition Chinese medicine of the present invention is 1 with the ratio of adjuvant: 500-1: 900.
Best pharmaceutical composition Chinese medicine of the present invention is 1 with the ratio of adjuvant: 600-1: 800.
The content of preparation of Chinese medicine of the present invention calculates with huperzine A, be 0.03-1% (weight ratio), or 30-300 μ g/ sheet/, wherein mainly be for adult's usefulness the 100ug/ sheet/, the 200ug/ sheet/and the child with the 50ug/ sheet/.The ratio of the adjuvant of pharmaceutical composition of the present invention and amount of drug all is in pharmaceutics and the pharmacopeia allowed band, feeds intake by metering, makes every/the huperzine A content in the huperzine medicine A reach the requirement (50 μ g-200 μ g/ sheets /) of pharmacopeia regulation.The prepared huperzine A preparation of the present invention has easy, the steady quality of preparation, and clinical administration is convenient, can be oral, characteristics such as buccal, and easy to use, good to schizophrenic and gerontal patient's compliance.
The present invention is based on dissolution with solvents dispersion method and solid, liquid dispersion method technology mutually, adopt the following step manufacturing:
A: with 1 weight portion huperzine A and 100 to 400 parts by weight solvent through being dissolved into the homogeneous solution of huperzine A hydrochlorate, add proper amount of surfactant, process for dispersing by disperseing spray to add joins in the substrate of 500 to 2000 weight portions, stirs, dry, after the interpolation lubricant stirs, direct compression, drying, make huperzine A orally disintegrating tablets or sheet, this huperzine A dispersed mixture also can become the huperzine A capsule agent by the fill capsule.
B: with 1 weight portion huperzine A and 100 to 400 parts by weight solvent through being dissolved into the homogeneous solution of huperzine A hydrochlorate; add proper amount of surfactant; process for dispersing by disperseing spray to add joins in the substrate of 500 to 2000 weight portions, stirs; granulate in granulator by wet granulation process; drying adds mix lubricant, tabletting; drying is made huperzine A orally disintegrating tablets or sheet.
C: or with 1 weight portion huperzine A and 100 to 400 parts by weight solvent through being dissolved into the homogeneous solution of huperzine A hydrochlorate, add proper amount of surfactant, stir; add in the substrate that fusion stirs, stir, cooling; pulverize, become huperzine-A solid to disperse thing, it is even to add an amount of adjuvant, mix lubricant; direct compression or in granulator, granulate by wet granulation process; drying adds mix lubricant, tabletting; drying is made huperzine A orally disintegrating tablets or sheet.
D: the huperzine-A solid that the C method is made disperses thing to add an amount of adjuvant, and mix lubricant is even, becomes capsule by fill.
Specific implementation method
One, example 1
Prescription:
Huperzine A 0.1g
Ethyl cellulose 6.0g
Starch 20g
Mannitol 20g
Hyprolose 20g
The sweet 0.5g of A Siba
Polyoxyethylene sorbitan monoleate 0.1g
Dilute hydrochloric acid ethanol 20ml
Magnesium stearate 0.5g
Make 1000
Method for making: huperzine A is dissolved in contains in the dilute hydrochloric acid ethanol.Fully dissolving adds polyoxyethylene sorbitan monoleate, stirs, become the dispersion ethanol liquid of huperzine A, spray add ethyl cellulose, starch, mannitol, hyprolose, the A Siba of mix homogeneously sweet in, be stirred well to evenly, in addition farinaceous size 20 orders are granulated, 60 ℃ dry down, 20 order granulate add the magnesium stearate mix homogeneously, tabletting, drying, promptly.
Two, example 2
Prescription:
Huperzine A 0.1g
Cross-linking sodium carboxymethyl cellulose 5.0g
Micropowder silica gel 0.6g
Mannitol 40g
The sweet 0.5g of A Siba
Polyvinylpyrrolidone 5g
Magnesium stearate 1g
Polyoxyethylene sorbitan monoleate 0.1g
Ethanol 20ml
Make 1000
Method for making: huperzine A is dissolved in the ethanol.Fully dissolving, add polyoxyethylene sorbitan monoleate, stir, become the dispersion ethanol liquid of huperzine A, spray adds in the adjuvant of cross-linking sodium carboxymethyl cellulose, micropowder silica gel, mannitol, polyvinylpyrrolidone and the sweet composition of A Siba of mix homogeneously, is stirred well to evenly, dry, add the magnesium stearate mix homogeneously, direct compression, promptly.
Three, example 3,
Prescription
Huperzine A 0.2g
Micropowder silica gel 37g
Mannitol 25g
Starch 35g
Polyoxyethylene sorbitan monoleate 0.1g
Dilute hydrochloric acid ethanol 20ml
Make 1000 capsules
Method for making: huperzine A is dissolved in fully dissolving in the ethanol, add polyoxyethylene sorbitan monoleate, stir, become the dispersion ethanol liquid of huperzine A, add in the adjuvant of micropowder silica gel, mannitol, starch and the composition of mix homogeneously, be stirred well to evenly, dry, promptly get the huperzine A dispersed mixture, incapsulate, promptly get huperzine A capsule.
Four, example 4
Prescription
Huperzine A 0.2g
Macrogol 4000 15g
Polyoxyethylene stearate (40) ester 5g
Cross-linking sodium carboxymethyl cellulose 5g
Mannitol 25g
The sweet 0.5g of A Siba
Magnesium stearate 0.5g
Polyoxyethylene sorbitan monoleate 0.1g
Dilute hydrochloric acid ethanol 20ml
Make 1000
Method for making: huperzine A is dissolved in the dilute hydrochloric acid ethanol, fully dissolving, add polyoxyethylene sorbitan monoleate, stir, become the dispersion ethanol liquid of huperzine A, add 80 ℃ of fused Macrogol 4000, polyoxyethylene stearates { in the substrate that the 40} ester is formed down, be stirred well to evenly, cooling becomes huperzine-A solid and disperses thing, pulverize and add mix homogeneously cross-linking sodium carboxymethyl cellulose, and the adjuvant of the sweet composition of A Siba in, be stirred well to evenly, add the magnesium stearate mix homogeneously, tabletting, drying promptly gets the huperzine A sheet.
Five, example 5,
Prescription
Huperzine A 0.2g
Macrogol 4000 15g
Polyoxyethylene stearate (40) ester 5g
Mannitol 25g
Micropowder silica gel 15g
Starch 40g
Polyoxyethylene sorbitan monoleate 0.1g
Dilute hydrochloric acid ethanol 20ml
Make 1000 capsules
Method for making: huperzine A is dissolved in the dilute hydrochloric acid ethanol, and fully dissolving adds polyoxyethylene sorbitan monoleate, stir, become the dispersion ethanol liquid of huperzine A, adding, 80 ℃ of following fused Macrogol 4000s, polyoxyethylene stearates { in the substrate that the 40} ester is formed, are stirred well to evenly, cooling, become huperzine-A solid and disperse thing, pulverize and add in the micropowder silica gel of mix homogeneously, the adjuvant that starch is formed, be stirred well to evenly, in incapsulating, promptly get huperzine A capsule.
Six, example 6,
Prescription:
Huperzine A 0.2g
Polyethylene glycol 6000 10g
Macrogol 4000 10g
Cross-linking sodium carboxymethyl cellulose 5g
Microcrystalline Cellulose 10g
Mannitol 25g
The sweet 0.5g of A Siba
Magnesium stearate 0.5g
Polyoxyethylene sorbitan monoleate 0.1g
Dilute hydrochloric acid ethanol 20ml
Make 1000
Method for making: huperzine A is dissolved in the dilute hydrochloric acid ethanol, fully dissolving, add polyoxyethylene sorbitan monoleate, stir, become the dispersion ethanol liquid of huperzine A, add 80 ℃ of fused Macrogol 4000, polyoxyethylene stearates { in the substrate that the 40} ester is formed down, be stirred well to evenly, cooling becomes huperzine-A solid and disperses thing, pulverize and add mix homogeneously cross-linking sodium carboxymethyl cellulose, and the adjuvant of the sweet composition of A Siba in, be stirred well to evenly, add the magnesium stearate mix homogeneously, tabletting, drying promptly gets the huperzine A sheet.
Seven, example 7
Prescription
Huperzine A 0.2g
Polyethylene glycol 6000 10g
Macrogol 4000 10g
Cross-linking sodium carboxymethyl cellulose 5g
Microcrystalline Cellulose 10g
Starch 60g
Micropowder silica gel 15g
Polyoxyethylene sorbitan monoleate 0.1g
Dilute hydrochloric acid ethanol 20ml
Make 1000 capsules
Method for making: huperzine A is dissolved in the dilute hydrochloric acid ethanol, fully dissolving, add polyoxyethylene sorbitan monoleate, stir, become the dispersion ethanol liquid of huperzine A, add 80 ℃ down in the substrate of fused polyethylene glycol 6000, Macrogol 4000, composition, be stirred well to evenly, cooling becomes huperzine-A solid and disperses thing, pulverize and add mix homogeneously cross-linking sodium carboxymethyl cellulose, and the adjuvant formed of microcrystalline Cellulose, starch in, be stirred well to evenly, add the micropowder silica gel mix homogeneously, drying, incapsulate, promptly get huperzine A capsule.
Eight, example 8
Prescription:
Huperzine A 0.1g
Ethyl cellulose 6.5g
Starch 20g
Mannitol 20g
The sweet 0.5g of A Siba
Polyvinylpyrrolidone 2g
Polyoxyethylene sorbitan monoleate 0.1g
Dilute hydrochloric acid ethanol 20ml
Magnesium stearate 0.5g
Make 1000
Method for making: huperzine A is dissolved in the dilute hydrochloric acid ethanol.Fully dissolving adds polyoxyethylene sorbitan monoleate, stirs, become the dispersion ethanol liquid of huperzine A, spray add ethyl cellulose, starch, mannitol, the A Siba of mix homogeneously sweet in, be stirred well to evenly, granulate with polyvinylpyrrolidone alcoholic solution 20 orders, 60 ℃ dry down, 18-20 order granulate adds the magnesium stearate mix homogeneously, tabletting, drying, promptly.
Nine, example 9
Prescription: (compound recipe huperzine A sheet)
Huperzine A 0.1g
Clozapine 25g
Ethyl cellulose 6.5g
Starch 20g
Mannitol 20g
Polyvinylpyrrolidone 2g
Polyoxyethylene sorbitan monoleate 0.1g
Dilute hydrochloric acid ethanol 5.0ml
30% Diluted Alcohol 15ml
Magnesium stearate 0.5g
Make 1000
Method for making: huperzine A is dissolved in the dilute hydrochloric acid ethanol.Fully dissolving adds polyoxyethylene sorbitan monoleate, stirs, become the dispersion ethanol liquid of huperzine A, spray adds in the clozapine, ethyl cellulose, starch, mannitol of mix homogeneously, is stirred well to evenly, granulates with polyvinylpyrrolidone alcoholic solution 20 orders, 60 ℃ dry down, 18-20 order granulate adds the magnesium stearate mix homogeneously, tabletting, drying promptly gets compound recipe huperzine A sheet.
Ten, example 10
Prescription: (compound recipe huperzine A capsule)
Huperzine A 0.2g
Clozapine 25g
Polyethylene glycol 6000 10g
Macrogol 4000 10g
Microcrystalline Cellulose 10g
Starch 30g
Micropowder silica gel 15g
Polyoxyethylene sorbitan monoleate 0.1g
Dilute hydrochloric acid ethanol 20ml
Make 1000 capsules
Method for making: huperzine A is dissolved in the dilute hydrochloric acid ethanol, fully dissolving, add polyoxyethylene sorbitan monoleate, stir, become the dispersion ethanol liquid of huperzine A, add 80 ℃ down in the substrate of fused polyethylene glycol 6000, Macrogol 4000, composition, be stirred well to evenly, cooling becomes huperzine-A solid and disperses thing, pulverize and add mix homogeneously clozapine, and the adjuvant formed of microcrystalline Cellulose, starch in, be stirred well to evenly, add the micropowder silica gel mix homogeneously, drying, incapsulate, promptly get huperzine A capsule.
Claims (10)
1. huperzine A preparation and the manufacture method thereof used of treatment schizophrenia and nervous function damage: it is characterized in that 1 weight portion huperzine A and 100 to 400 parts by weight solvent through being dissolved into the stable saline solution that becomes, then according to the following steps:
A. add in 300 to the 1000 weight portion substrate by the method for disperseing spray to add, mixing and stirring adds lubricant by direct compression process, and tabletting is drying to obtain huperzine A sheet/oral cavity disintegration tablet.
B. add in 300 to the 1000 weight portion substrate by the method for disperseing spray to add, mixing and stirring adds suitable amount of adhesive, wet granulation, and drying adds lubricant, mix homogeneously, tabletting is drying to obtain huperzine A sheet/oral cavity disintegration tablet.
C. add in 300 to the 1000 weight portion substrate by the method for disperseing spray to add, mixing and stirring is directly advanced capsule filling machine and is filled, and makes huperzine A capsule.
D. add in 100 to the 500 weight portion molten matrix by the method for preparing solid dispersion, cooling is pulverized, make solid dispersion, add again in 100 to the 300 weight portion substrate and stir, add lubricant, mix homogeneously, tabletting is drying to obtain huperzine A sheet/oral cavity disintegration tablet.
E. add in 100 to the 500 weight portion molten matrix by the method for preparing solid dispersion, cooling is pulverized, and makes solid dispersion, adds in 100 to the 300 weight portion substrate to stir again, and enters capsule filling machine and fills, and makes huperzine A capsule.
2. huperzine A according to claim 1, its molecular formula are C
15H
18N
2O, molecular weight are 242.32.Huperzine A has very strong inhibition cholinesterase activity and true acetylcholine esterase is had stronger selectivity inhibition pharmacological action.Huperzine A also has the oxidative stress toxicity that improves the generation of cholinergic neuron function and protecting neuronal cell antagonism beta-amyloyd peptide and brings out the apoptosis effect; obvious to improving cognition, memory and behavior effect, and the patient had the function that improves study, memory effect.Clinical trial proof huperzine A has remarkable result to treatment schizophrenia, and is effective to the treatment of the inflammation of inflammation in the cerebral hemorrhage and cerebral ischemia.
3. solvent according to claim 1 includes but not limited to dilute hydrochloric acid, ethanol, acetone, glycerol, propylene glycol etc.
4. substrate according to claim 1 includes but not limited to polyethylene glycol 6000, Macrogol 4000, polyethylene glycol 1500, polyoxyethylene stearate (40) ester, hydroxypropyl emthylcellulose (HPMC), ethyl cellulose (HEC), HPMC (HPC-Na), cross-linking sodium carboxymethyl cellulose, polyvinylpyrrolidone, polyoxyethylene sorbitan monoleate, citric acid, xylitol, sorbitol, mannitol, corn starch, dextrin, microcrystalline Cellulose, micropowder silica gel, magnesium stearate, gelatin, arabic gum, alginic acid.And the sweet and essence of A Siba.
5. huperzine A sheet/oral cavity disintegration tablet according to claim 1/capsule preparations is characterized in that the adjuvant and the ratio of the weight of huperzine A are 300: 1-1000: 1.Wherein in the preparation with the cubage of huperzine A be 30-300 μ g/ sheet/.
6. according to the described huperzine A sheet/oral cavity disintegration tablet of claim 1-4/capsule preparations, it is characterized in that solvent and huperzine A weight ratio be 100: 1-400: 1.
7. according to the described huperzine A sheet/oral cavity disintegration tablet of claim 1-4/preparations such as capsule, it is characterized in that it is by adding an amount of dissolution with solvents with huperzine A that huperzine-A solid disperses thing, after forming stable one-tenth saline solution, add in the molten matrix, cooling stirs, pulverize, make uniform solid dispersion.
8. the described huperzine A sheet/oral cavity disintegration tablet of claim 1-5/capsular preparation method, huperzine A preparation of the present invention also can with include but not limited to that clozapine, olanzapine etc. combine at interior medicine and make compound recipe huperzine A sheet/oral cavity disintegration tablet/preparations such as capsule, to improve medication effect and compliance.
9. according to the described huperzine A sheet/oral cavity disintegration tablet of claim 1-4/capsule preparations, its feature may further comprise the steps in preparation method:
(1) accurately take by weighing huperzine A, various adjuvant is standby.
(2) solvent is added dropwise to huperzine A, stirring and dissolving evenly form stable one-tenth saline solution earlier, add proper amount of surfactant again, stir, and be standby.
(3) A: the huperzine A solution of (2) spray is added in the mixture that adjuvant forms, disperse to stir, the time is 10-60 minute, treat that huperzine A is uniformly dispersed after, drying is added lubricant, stirs, be used for directly compacting in flakes/oral cavity disintegration tablet.
B: the huperzine A solution spray of (2) is added in the mixture of adjuvant composition, dispersion stirs, and the time is 10-60 minute, treat that the huperzine A hydrojet is uniformly dispersed after, add binding agent, solvent is an amount of, the system that stirs soft material is also crossed 18 orders and granulated, and is dry under 30-80 ℃ of temperature, 18-20 mesh sieve granulate, promptly get the huperzine A granule, get the huperzine A granule, add the 0.5-1% lubricant, mix homogeneously.Get the huperzine A granule of mix homogeneously, tabletting dry 24 hours, promptly gets huperzine A sheet/oral cavity disintegration tablet.
C: the huperzine A solution of (2) is added in the molten matrix, disperse to stir cooling, pulverize, make into huperzine-A solid and disperse thing, add in the mixture of forming by other adjuvants, dispersion stirs, and the time is 10-60 minute, treat that huperzine A is uniformly dispersed after, add binding agent, solvent is an amount of, stir, the system soft material is also crossed 20 orders and granulated, and is dry under 30-60 ℃ of temperature, 18 mesh sieve granulate promptly get the huperzine A granule.Get the huperzine A granule, add the 0.5-1% lubricant, mix homogeneously.Get the huperzine A granule of mix homogeneously, tabletting dry 24 hours, promptly gets huperzine A sheet/oral cavity disintegration tablet.
(4) the huperzine A solution of (2) spray is added in the mixture that adjuvant forms, disperse and stir, the time is 10-60 minute, after treating that huperzine A is uniformly dispersed, drying is added lubricant, stir, directly enter capsule filling machine and fill, make capsule.
(5) the huperzine A solution of (2) is added in the molten matrix, disperse to stir cooling, pulverize, make into huperzine-A solid and disperse thing, add in the mixture of forming by adjuvant, dispersion stirs, and the time is 10-60 minute, treat that huperzine A is uniformly dispersed after, add binding agent, solvent is an amount of, stir, the system soft material is also crossed 18 orders and granulated, and is dry under 30-60 ℃ of temperature, 20 mesh sieve granulate promptly get the huperzine A granule.Get the huperzine A granule, add lubricant, mix homogeneously will be filled to huperzine A capsule in this hybrid particles adding capsule filling machine.
10. the described huperzine A orally disintegrating tablets/oral cavity disintegration tablet of claim 9/capsular preparation method, it is characterized in that adopting the liquid dispersion method earlier with the huperzine A homodisperse, form stable one-tenth saline solution, adopt solid dispersion technology to be scattered in huperzine A in the substrate fully again, adjuvant compound particles baking temperature is 30-80 ℃, 30-120 minute, that is: treat that huperzine A is uniformly dispersed after, add binding agent, solvent is an amount of, the system that stirs soft material is also crossed 18 orders and is granulated, dry under 30-80 ℃ of temperature, 20 mesh sieve granulate promptly get the huperzine A granule.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2011079766A1 (en) * | 2009-12-29 | 2011-07-07 | 上海中西制药有限公司 | Aripiprazole solid preparation and the production method thereof |
| CN104116719A (en) * | 2014-07-18 | 2014-10-29 | 湖南本草制药有限责任公司 | Huperzine A modified-release tablet composition and preparation method thereof |
| CN106511348A (en) * | 2016-11-02 | 2017-03-22 | 中山大学 | Huperzine-A framework particles, orally disintegrating tablets and preparation methods thereof |
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2010
- 2010-01-06 CN CN201010003976A patent/CN101804038A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011079766A1 (en) * | 2009-12-29 | 2011-07-07 | 上海中西制药有限公司 | Aripiprazole solid preparation and the production method thereof |
| CN104116719A (en) * | 2014-07-18 | 2014-10-29 | 湖南本草制药有限责任公司 | Huperzine A modified-release tablet composition and preparation method thereof |
| CN104116719B (en) * | 2014-07-18 | 2016-06-22 | 湖南本草制药有限责任公司 | A kind of huperzine A is adjusted and is released tablet composition and preparation method thereof |
| CN106511348A (en) * | 2016-11-02 | 2017-03-22 | 中山大学 | Huperzine-A framework particles, orally disintegrating tablets and preparation methods thereof |
| CN106511348B (en) * | 2016-11-02 | 2019-04-19 | 中山大学 | Huperzine skeleton particle, oral disintegrating tablet and preparation method thereof |
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