CN101732312A - Huperzine A oral formulation and a preparation method thereof - Google Patents
Huperzine A oral formulation and a preparation method thereof Download PDFInfo
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- CN101732312A CN101732312A CN200910272934A CN200910272934A CN101732312A CN 101732312 A CN101732312 A CN 101732312A CN 200910272934 A CN200910272934 A CN 200910272934A CN 200910272934 A CN200910272934 A CN 200910272934A CN 101732312 A CN101732312 A CN 101732312A
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Abstract
The invention relates to a huperzine A oral formulation and a preparation method thereof. The formulation is prepared from huperzine A and officinal auxiliary materials, wherein the officinal auxiliary materials comprise water-insoluble excipient, disintegrant, adhesive and lubricant. The formulation is prepared from the following components by weight percentage: 0.005-1% of huperzine A, 0.1-99% of water-insoluble excipient, 0.1-10% of adhesive, 0.1-80% of disintegrant and 0.1-10% of lubricant. The invention improves the compliance of patients on the medicament and enhances the bioavailability of the medicament.
Description
Technical field
The present invention relates to a kind of dosage form of medicine, relate in particular to a kind of huperzine A oral formulation and preparation method thereof.
Background technology
At present, in the whole world fifties00000000 populations, have 400,000,000 people to enter old age approximately, in 50 years of future, old people's quantity will be doubled and redoubled.With the U.S. is example, and during by 2005, the old people who surpasses 65 years old is about 16%～22% of total population, and promptly the people of the U.S. above 65 years old will be increased to 1/5 by 1/9 of the past.In these people, there is 12% people all to have the learning and memory obstacle of certain form approximately, the U.S. has 5,000,000 potential patients approximately.The old man of China more than 60 years old, 3.2% suffers from primary disease.Along with the aging of world population, this disease becomes and causes one of old three invalid big diseases.Yet medically also there is not effective way to conquer this disease, the research and development of antidementia agent has caused the great attention of countries in the world the world of medicine, and that the alkaloid-huperzine A that extracts from important Herba Lycopodii serrati seems in such medicine is especially eye-catching, has caused global concern.The Chinese medicine Herba Lycopodii serrati is the herb of Huperziaceae plants of Huperzia Herba Lycopodii serrati, different name: lousewort, short Cunninghamia lanceolata (Lamb.) Hook., louse mother-in-law medicine, help king, life pull.The Herba Lycopodii serrati beginning is stated from " Zhiwu Mingshi Tukao ", nature and flavor suffering, hardship, flat.Existing dissipating blood stasis for subsidence of swelling, detoxifcation, analgesic effect.Shanghai in 1975 and Zhejiang psychosis prevention institute use in Herba Lycopodii serrati decoct and the total alkali tablet in treatment schizophrenia process, find patient's cholinergic system excitation in various degree.Institute of materia medica, the Academy of Medical Sciences, nineteen eighty-two Zhejiang cooperates with the Shanghai Pharmaceutical Inst., Chinese Academy of Sciences, in numerous positions and monomer, finds two high activities to suppress cholinesterase (ChE) new alkaloids-huperzine A (Hup-A) and huperzine B.Began to be used for senile dementia treatment research in 1985.Because the acting duration of huperzine A is long, toxicity is few, is subjected to attracting attention of countries in the world colleague.
Huperzine A (Huperzine-A, HupA, 1) is a kind of potent reversibility cholinesterase inhibitor, has fat-soluble height, easily by characteristics such as blood-brain barriers, to the selective inhibitory action of true cholinesterase, the clinical Therapy for Myasthemia Gravis that is mainly used in, it can improve senile memory function and go down, can significantly improve Alzheimer thatch disease (Alzheimer` sdisease, AD) patient's memory, cognition and behavioral function are not found tangible untoward reaction, are the prospect medicines of a kind of AD of treatment.1993, it was gone on the market by the FDA approval in the U.S.; 1996, it was two kind new medicines that China ratifies its oral tablet, and was used for the treatment of AD, be the 2nd generation acetylcholinesterase inhibitor.
Huperzine A is applicable to the following disease of treatment:
1. treatment Alzheimer
2. myasthenia gravis
3. senile memory function goes down
4. geratic period dysmnesia
5. alzheimer disease
6. vascular dementia
7. normal adolescence student memory
8.HuP-A treatment iodine deficient area mental retardation
9. treat light medium-sized craniocerebral trauma memory and cognitive disorder
10. treatment children's development of speech is slow
The back amnestic syndrome 11. treatment CO poisons
12. treatment schizophrenia in convalescent stage patient dysmnesia
Huperzine A be (5R, 9R, 11E)-5-amino-11-ethylidene-5,8,9,10-tetrahydrochysene-7-methyl-5,9-methylene cycloocta (b) pyridine-2 (1H)-ketone, the crystalline powder of white or off-white color; Easily molten in methanol, in ethanol, dissolve, insoluble in water; Slightly soluble in the 0.01mol/L hydrochloric acid solution, its PKTa are 6.18.Because this product is used for senile dementia and patient with phychlogical problems more, existing peroral dosage form in use patient's compliance is poor, the huperzine A dispersible tablet can improve the compliance of medicine preferably, and existing market yet there are no the report of huperzine A dispersible tablet.
Summary of the invention
The object of the present invention is to provide a kind of huperzine A oral formulation that can improve patient dependence.
Another object of the present invention is to provide a kind of preparation method of huperzine A oral formulation.
A kind of huperzine A oral formulation of the present invention comprises huperzine A and pharmaceutically useful adjuvant, and the percentage by weight of its each component is: huperzine A 0.005～1%, pharmaceutically useful adjuvant are remainder.
Pharmaceutically useful adjuvant, comprise: water-insoluble excipient, disintegrating agent, binding agent, lubricant, its percentage by weight that accounts for the preparation total amount is respectively: water-insoluble excipient 0.1～99%, disintegrating agent 0.1～80%, binding agent 0.1～10%, lubricant 0.1～10%.
Each component preferred weight percent is in this huperzine A oral formulation: huperzine A 0.01～0.1%, water-insoluble excipient 60～90%, disintegrating agent 1～20%, binding agent 0.5～2%, lubricant 0.5～5%.
Described huperzine A oral formulation is prepared into the dispersion tablet.
Described water-insoluble excipient is one or more mixing in starch, microcrystalline Cellulose, the pregelatinized Starch; Its mixed proportion is an arbitrary proportion.
Described disintegrating agent is one or more mixing in hydroxyethyl-cellulose, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, hydroxypropyl emthylcellulose, starch and the derivant thereof; Its mixed proportion is an arbitrary proportion.
Described binding agent is one or more mixing in hypromellose, sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30, the starch slurry; Its mixed proportion is an arbitrary proportion.
Described lubricant is one or more mixing in calcium stearate, magnesium stearate, micropowder silica gel, the Pulvis Talci; Its mixed proportion is an arbitrary proportion.
Best proportioning is that 1000 dispersible tablets comprise following component: huperzine A 0.05g, microcrystalline Cellulose 60g, pregelatinized Starch 26g, cross-linking sodium carboxymethyl cellulose 10g, micropowder silica gel 3g, magnesium stearate 1g, 30 POVIDONE K 30 BP/USP are 30 an amount of, water is an amount of.
The preparation method of a kind of huperzine A oral formulation of the present invention, its step is as follows: at first supplementary material was pulverized 80 mesh sieves, take by weighing principal agent, excipient, disintegrating agent by recipe quantity, fully mix, add the aqueous solution or the alcoholic solution system soft material of binding agent preparation, 40 ℃～70 ℃ dryings 2～8 hours, granulate, add lubricant, mix homogeneously, tabletting forms dispersible tablet.
A kind of huperzine A oral formulation of the present invention and preparation method thereof, its advantage is: adopted conventional preparation technology and pharmaceutically useful adjuvant to prepare the pharmaceutical formulation that improves patient dependence, and this dosage form is fast than the general formulation absorption, it is high that bioavailability is wanted.
The specific embodiment
Embodiment one
A kind of huperzine A oral formulation of the present invention prepares 1000 huperzine A dispersible tablets (specification: every contains huperzine A 0.05mg), uses following compositions:
The name of material inventory
Huperzine A 0.05g
Microcrystalline Cellulose 59.5g
Pregelatinized Starch 26g
Carboxymethyl starch sodium 10g
Micropowder silica gel 3g
Magnesium stearate 1g
30 POVIDONE K 30 BP/USP 30 0.45g
Make 1000
Processing step: supplementary material was pulverized 80 mesh sieves, take by weighing huperzine A 0.05g, microcrystalline Cellulose 59.5g, pregelatinized Starch 26g, sodium carboxymethyl cellulose 10g by recipe quantity, fully mix, the aqueous solution system soft material that adds polyvidone K30 0.45g preparation, 70 ℃ of dryings 3 hours, granulate adds micropowder silica gel 3g, magnesium stearate 1g, mix homogeneously, tabletting obtain the huperzine A dispersible tablet.
Embodiment two
A kind of huperzine A oral formulation of the present invention prepares 1000 huperzine A dispersible tablets (specification: every contains huperzine A 0.08mg), uses following compositions:
The name of material inventory
Huperzine A 0.08g
Microcrystalline Cellulose 85.5g
Low-substituted hydroxypropyl cellulose 10g
Micropowder silica gel 3g
Magnesium stearate 1g
Starch slurry 0.42g
Make 1000
Processing step: supplementary material was pulverized 80 mesh sieves, take by weighing huperzine A 0.08g, microcrystalline Cellulose 85.5g, low-substituted hydroxypropyl cellulose 10g by recipe quantity, fully mix, the starch slurry 0.42 system soft material that adds the starch preparation, 40 ℃ of dryings 6 hours, granulate adds micropowder silica gel 3g, magnesium stearate 1g, mix homogeneously, tabletting obtain the huperzine A dispersible tablet.
Embodiment three
A kind of huperzine A oral formulation of the present invention prepares 1000 huperzine A dispersible tablets (specification: every contains huperzine A 0.1mg), uses following compositions:
The name of material inventory
Huperzine A 0.1g
Microcrystalline Cellulose 75g
Pregelatinized Starch 15g
Hydroxyethyl-cellulose 4g
Pulvis Talci 1g
Calcium stearate 3g
Hypromellose 2g
Make 1000
Processing step: supplementary material was pulverized 80 mesh sieves, take by weighing huperzine A 0.1g, microcrystalline Cellulose 75g, pregelatinized Starch 15g, hydroxyethyl-cellulose 4g by recipe quantity, fully mix, the alcoholic solution system soft material that adds hypromellose 2g preparation, 55 ℃ of dryings 5 hours, granulate adds Pulvis Talci 1g, calcium stearate 3g, mix homogeneously, tabletting obtain the huperzine A dispersible tablet.
Embodiment four
A kind of huperzine A oral formulation of the present invention prepares 1000 huperzine A dispersible tablets (specification: every contains huperzine A 0.1mg), uses following compositions:
The name of material inventory
Huperzine A 0.01g
Microcrystalline Cellulose 35g
Starch 20g
Polyvinylpolypyrrolidone 30g
Magnesium stearate 5g
Pulvis Talci 4g
Sodium carboxymethyl cellulose 6g
Make 1000
Processing step: supplementary material was pulverized 80 mesh sieves, take by weighing huperzine A 0.01g, microcrystalline Cellulose 35g, starch 20g, polyvinylpolypyrrolidone 30g by recipe quantity, fully mix, the aqueous solution system soft material that adds sodium carboxymethyl cellulose 6g preparation, 60 ℃ of dryings 4 hours, granulate adds Pulvis Talci 4g, magnesium stearate 5g, mix homogeneously, tabletting obtain the huperzine A dispersible tablet.
Embodiment five
A kind of huperzine A oral formulation of the present invention prepares 1000 huperzine A dispersible tablets (specification: every contains huperzine A 0.3mg), uses following compositions:
The name of material inventory
Huperzine A 0.3g
Pregelatinized Starch 60g
30 POVIDONE K 30 BP/USP 30 3g
Sodium carboxymethyl cellulose 3g
Starch slurry 3g
Polyvinylpolypyrrolidone 15g
Hydroxypropyl emthylcellulose 10g
Micropowder silica gel 3g
Calcium stearate 3g
Make 1000
Processing step: at first supplementary material was pulverized 80 mesh sieves, take by weighing huperzine A 0.3g, pregelatinized Starch 60g, polyvinylpolypyrrolidone 15g, hydroxypropyl emthylcellulose 10g by recipe quantity, fully mix, the alcoholic solution system soft material that adds polyvidone K30 3g, sodium carboxymethyl cellulose 3g, starch slurry 3g preparation, 50 ℃ of dryings 7 hours, granulate adds micropowder silica gel 3g, calcium stearate 3g, mix homogeneously, tabletting obtain the huperzine A dispersible tablet.
Embodiment six
A kind of huperzine A oral formulation of the present invention prepares 1000 huperzine A dispersible tablets (specification: every contains huperzine A 0.9mg), uses following compositions:
The name of material inventory
Huperzine A 0.9g
Pregelatinized Starch 40g
Microcrystalline Cellulose 40g
Sodium carboxymethyl cellulose 2g
Hypromellose 2g
Hydroxyethyl-cellulose 6g
The low hydroxypropyl cellulose 8g that gets
Micropowder silica gel 1g
Make 1000
Processing step: at first supplementary material was pulverized 80 mesh sieves, take by weighing huperzine A 0.9g, pregelatinized Starch 40g, microcrystalline Cellulose 40g, hydroxyethyl-cellulose 6g, the low hydroxypropyl cellulose 8g that gets by recipe quantity, fully mix, the aqueous solution system soft material that adds sodium carboxymethyl cellulose 2g, hypromellose 2g preparation, 65 ℃ of dryings 3.5 hours, granulate adds micropowder silica gel 1g, mix homogeneously, tabletting obtain the huperzine A dispersible tablet.
Embodiment seven
A kind of huperzine A oral formulation of the present invention prepares 1000 huperzine A dispersible tablets (specification: every contains huperzine A 0.05mg), uses following compositions:
The name of material inventory
Huperzine A 0.5g
Pregelatinized Starch 45g
Microcrystalline Cellulose 25g
30 POVIDONE K 30 BP/USP 30 4.5g
Polyvinylpolypyrrolidone 5g
Hydroxypropyl emthylcellulose 6g
The low hydroxypropyl cellulose 4g that gets
Calcium stearate 5g
Magnesium stearate 5g
Make 1000
At first supplementary material was pulverized 80 mesh sieves, take by weighing huperzine A 0.5g, pregelatinized Starch 45g, microcrystalline Cellulose 25g, polyvinylpolypyrrolidone 5g, hydroxypropyl emthylcellulose 6g, the low hydroxypropyl cellulose 4g that gets by recipe quantity, fully mix, the alcoholic solution system soft material that adds polyvidone K30 4.5g preparation, 45 ℃ of dryings 6.5 hours, granulate adds calcium stearate 5g, magnesium stearate 5g, mix homogeneously, tabletting obtain the huperzine A dispersible tablet.
The invention is not restricted to above embodiment, can finish the embodiment of multiple combination as required.
Claims (8)
1. huperzine A oral formulation, it is characterized in that: comprise huperzine A and pharmaceutically useful adjuvant, the percentage by weight of its each component is: huperzine A 0.005～1%, pharmaceutically useful adjuvant are remainder.
2. a kind of huperzine A oral formulation according to claim 1, it is characterized in that pharmaceutically useful adjuvant, comprise: water-insoluble excipient, disintegrating agent, binding agent, lubricant, its percentage by weight that accounts for the preparation total amount is respectively: water-insoluble excipient 0.1～99%, disintegrating agent 0.1～80%, binding agent 0.1～10%, lubricant 0.1～10%.
3. a kind of huperzine A oral formulation according to claim 1 is characterized in that: each component preferred weight percent is: huperzine A 0.01～0.1%, water-insoluble excipient 60～90%, disintegrating agent 1～20%, binding agent 0.5～2%, lubricant 0.5～5%.
4. a kind of huperzine A oral formulation according to claim 2 is characterized in that: described water-insoluble excipient is one or more mixing in microcrystalline Cellulose, pregelatinized Starch and the starch; Its mixed proportion is an arbitrary proportion.
5. a kind of huperzine A oral formulation according to claim 2 is characterized in that: described disintegrating agent is one or more mixing in hydroxyethyl-cellulose, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, hydroxypropyl emthylcellulose, starch and the derivant thereof; Its mixed proportion is an arbitrary proportion.
6. a kind of huperzine A oral formulation according to claim 2 is characterized in that: described binding agent is one or more mixing in hypromellose, sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30, the starch slurry; Its mixed proportion is an arbitrary proportion.
7. a kind of huperzine A oral formulation according to claim 2 is characterized in that: described lubricant is one or more mixing in calcium stearate, magnesium stearate, micropowder silica gel, the Pulvis Talci; Its mixed proportion is an arbitrary proportion.
8. the preparation method of a huperzine A dispersible tablet, it is characterized in that: its step is as follows:
At first supplementary material was pulverized 80 mesh sieves, taken by weighing principal agent, water-insoluble excipient, disintegrating agent, fully mixed by recipe quantity, the aqueous solution or the alcoholic solution system soft material that add binding agent preparation, 40 ℃～70 ℃ dryings 2～8 hours, granulate, add lubricant, mix homogeneously, tabletting forms dispersible tablet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910272934A CN101732312A (en) | 2009-11-27 | 2009-11-27 | Huperzine A oral formulation and a preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910272934A CN101732312A (en) | 2009-11-27 | 2009-11-27 | Huperzine A oral formulation and a preparation method thereof |
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| CN101732312A true CN101732312A (en) | 2010-06-16 |
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| CN200910272934A Pending CN101732312A (en) | 2009-11-27 | 2009-11-27 | Huperzine A oral formulation and a preparation method thereof |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103356497A (en) * | 2013-08-05 | 2013-10-23 | 扬子江药业集团上海海尼药业有限公司 | Benzenesulfonate amlodipine tablet and preparation method thereof |
| CN103980198A (en) * | 2013-02-08 | 2014-08-13 | 复旦大学 | Alkaloid Casuarinine H and use thereof in preparation of medicines for treating neurodegenerative diseases |
| CN104352467A (en) * | 2014-11-17 | 2015-02-18 | 辰欣药业股份有限公司 | Huperzine A tablet and preparation method thereof |
| CN107233365A (en) * | 2017-06-21 | 2017-10-10 | 芜湖耄智生物科技有限公司 | Tablet containing huperzine and preparation method thereof |
| WO2018213838A1 (en) * | 2017-05-19 | 2018-11-22 | Biscayne Neurotherapeutics, Inc. | Modified release pharmaceutical compositions of huperzine and methods of using the same |
| US11351120B2 (en) | 2018-11-19 | 2022-06-07 | Supernus Pharmaceuticals, Inc. | Use of higher doses of modified release huperzine formulations |
-
2009
- 2009-11-27 CN CN200910272934A patent/CN101732312A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103980198A (en) * | 2013-02-08 | 2014-08-13 | 复旦大学 | Alkaloid Casuarinine H and use thereof in preparation of medicines for treating neurodegenerative diseases |
| CN103980198B (en) * | 2013-02-08 | 2016-09-07 | 复旦大学 | Alkaloid Casuarinine H and the purposes in preparation treatment nerve degenerative diseases medicine thereof |
| CN103356497A (en) * | 2013-08-05 | 2013-10-23 | 扬子江药业集团上海海尼药业有限公司 | Benzenesulfonate amlodipine tablet and preparation method thereof |
| CN104352467A (en) * | 2014-11-17 | 2015-02-18 | 辰欣药业股份有限公司 | Huperzine A tablet and preparation method thereof |
| WO2018213838A1 (en) * | 2017-05-19 | 2018-11-22 | Biscayne Neurotherapeutics, Inc. | Modified release pharmaceutical compositions of huperzine and methods of using the same |
| CN115715769A (en) * | 2017-05-19 | 2023-02-28 | 比斯坎神经治疗公司 | Modified release pharmaceutical compositions of huperzine and methods of use |
| CN107233365A (en) * | 2017-06-21 | 2017-10-10 | 芜湖耄智生物科技有限公司 | Tablet containing huperzine and preparation method thereof |
| US11351120B2 (en) | 2018-11-19 | 2022-06-07 | Supernus Pharmaceuticals, Inc. | Use of higher doses of modified release huperzine formulations |
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Open date: 20100616 |