CN1493287A - Shishan alkaloid drip pill and its preparation method - Google Patents

Abstract

A dripping pill of huperzine A and its superfine pulverizing process for preparing it are disclosed. Its advantages are high dissolving and disintegrating speed, high stripping percentage, quickly taking its effect, stability and low cost.

Description

Huperzine dropping pills and preparation method thereof

Technical field

The present invention relates to a kind of pharmaceutical product and preparation method thereof, specifically huperzine dropping pills and preparation method thereof.

Background technology

Huperzine A is a cholinesterase inhibitor, and true property ChE is had selective inhibitory, easily passes through blood brain barrier.Has the effect that promotes that memory represents and hypermnesis keep.

Zoopery shows that huperzine A oral absorbs rapidly and fully, and it is also fast to distribute, distribution phase half-life (t _{1/2 α}) be 9.8 minutes, the bioavailability height is drained slowly, eliminates phase half-life (t _{1/2 β}) be 247.5 minutes, mainly excrete with prototype and metabolite form by urine.The clinical benign memory deficits that are used for improve that the patient points to that memory, learning by association, image are recalled, random shape is re-recognized and ability such as portrait memory.The dysmnesia that dementia patients and brain organic pathological changes are caused also have the improvement effect.

The huperzine A oral formulation of list marketing at present has tablet and capsule.Because huperzine A is water insoluble, mildly bitter flavor has and draws moistly, and hydrophobicity is strong, huperzine A sheet or capsular disintegration time are long, dissolution and dissolution rate are low, absorption difference, and bioavailability is low, supplementary product consumption is big, child, old people, bed patient and dysphagia patients are taken inconvenience, and compliance is poor, have influenced the performance of huperzine A therapeutical effect.

The present invention makes the huperzine dropping pills agent by using ultramicro communication technique and dropping pill formulation Technology exactly, thereby overcomes huperzine A sheet and capsular above defective, and the therapeutical effect of huperzine A is given full play to.

Summary of the invention

The huperzine dropping pills of making by using ultramicro communication technique and dropping pill formulation Technology not only have disintegrate molten loose fast, dissolution and dissolution rate improve, steady quality, the pill volume is little, easy to carry and use, onset is rapid, compliance is good, be particularly suitable for the characteristics that child, old people, bed patient and dysphagia patients are taken, but also has working condition and production equipment is simple, production cost is low, compares the advantage that supplementary product consumption reduces with tablet or capsule, has demonstrated fully the new drug research exploitation spirit that people-oriented.

For achieving the above object, the present invention by the following technical solutions: 1 weight portion huperzine A and 50～200 weight portion carriers are added in 1～10 weight portion molten matrix through the fine powder of micronizing, fully mixing, dropping preparation method is condensed into ball in coolant, remove coolant, drying, promptly.

Among the present invention the chemical name of 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, molecular formula is C ₁₅H ₁₈N ₂O, molecular weight are 242.32, and structural formula is

Carrier among the present invention includes but not limited to mannitol, lactose, sorbitol, xylitol, sucrose, fructose, glucose, maltose, aminoacid etc.

Substrate among the present invention includes but not limited to polyethylene glycol 6000, Macrogol 4000, polyethylene glycol 1500, cetomacrogol 1000, sodium stearate, glycerin gelatine, poloxamer, stearic acid, glycerol monostearate acid, insect wax etc.

Coolant among the present invention includes but not limited to dimethicone, liquid paraffin, vegetable oil, water, alcoholic solution etc.

Below through detecting to beneficial effect of the present invention as directed

One, detects index and method

1. disintegrate (molten loosing) time limit: check according to inspection technique disintegration (two appendix XA of Chinese Pharmacopoeia version in 2000).

2. dissolution rate: sample thief, according to dissolution method (two appendix XC of Chinese Pharmacopoeia version in 2000 three therapeutic methods of traditional Chinese medicine), with 0.01mol/L hydrochloric acid solution 100ml is solvent, rotating speed is that per minute 100 changes, operation in the time of 5,10,20,30 and 45 minutes, is got solution 1ml in accordance with the law, filter, filtrate is as need testing solution.Other precision takes by weighing through 80 ℃ of huperzine A reference substances that are dried to constant weight an amount of, makes the solution that contains 0.5 μ g among every 1ml, product solution in contrast with above-mentioned dissolve with hydrochloric acid solution and dilution.Get each 20 μ l of above-mentioned two kinds of solution respectively and inject chromatograph of liquid, according to high performance liquid chromatography (two appendix VD of Chinese Pharmacopoeia version in 2000), with octadecane silane group silica gel is filler, with methanol-water (50: 50, contain 0.2% triethylamine) is mobile phase, and flow velocity is 1.0ml/min, column temperature is 40 ℃, the detection wavelength is 310nm, measures peak area in accordance with the law, calculates stripping quantity by external standard method.

Two, commercially available huperzine A sheet testing result

1. disintegration time: 63 minutes

2. dissolution rate:

Time (minute) 5 10 20 30 45

Dissolution (%) 17.6 32.3 51.4 68.9 72.5

Three, example 1 sample detection result

1. the molten diffusing time: 3 minutes

2. dissolution rate:

Time (minute) 5 10 20 30 45

Dissolution (%) 49.4 68.5 92.3 98.7 99.2

Four, example 2 sample detection results

1. the molten diffusing time: 3 minutes

2. dissolution rate:

Time (minute) 5 10 20 30 45

Dissolution (%) 51.4 70.3 90.6 99.7 98.9

Five, example 3 sample detection results

1. the molten diffusing time: 4 minutes

2. dissolution rate:

Time (minute) 5 10 20 30 45

Dissolution (%) 48.3 69.2 88.4 98.9 98.6

Six, example 4 sample detection results

1. the molten diffusing time: 7 minutes

2. dissolution rate:

Time (minute) 5 10 20 30 45

Dissolution (%) 53.6 72.3 94.5 98.9 100.3

Seven, example 5 sample detection results

1. the molten diffusing time: 13 minutes

2. dissolution rate:

Time (minute) 5 10 20 30 45

Dissolution (%) 40.3 58.6 79.2 96.5 98.7

Eight, example 6 sample detection results

1. the molten diffusing time: 19 minutes

2. dissolution rate

Time (minute) 5 10 20 30 45

Dissolution (%) 41.5 52.6 77.4 93.5 98.7

The specific embodiment

One, example 1

Prescription:

Huperzine A 50mg

Mannitol 5g

Polyethylene glycol 6000 15g

Make 1000

Method for making: the micronizing of learning from else's experience is crossed the huperzine A of 200 mesh sieves and the mixing fine powders of mannitol is added in the fused polyethylene glycol 6000 substrate, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.

Two, example 2

Prescription:

Huperzine A 50mg

Mannitol 5g

Macrogol 4000 15g

Make 1000

Method for making: the micronizing of learning from else's experience is crossed the huperzine A of 200 mesh sieves and the mixing fine powders of mannitol is added in the fused Macrogol 4000 substrate, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.

Three, example 3

Prescription:

Huperzine A 50mg

Mannitol 5g

Polyethylene glycol 6000 5g

Macrogol 4000 10g

Make 1000

Method for making: the mixing fine powders that the micronizing of learning from else's experience is crossed the huperzine A of 200 mesh sieves and mannitol is added to fused Macrogol 4000 and the polyethylene glycol 6000 elder brother closes in the substrate, stirs evenly, and be coolant with the dimethicone, the dropping preparation method pill, drying, promptly.

Four, example 4

Prescription:

Huperzine A 50mg

Mannitol 5g

Glyceryl monostearate 15g

Make 1000

Method for making: the micronizing of learning from else's experience is crossed the huperzine A of 200 mesh sieves and the mixing fine powders of mannitol is added in the fused glyceryl monostearate substrate, and mixing is a coolant with the frozen water, the dropping preparation method pill, and drying, promptly.

Five, example 5

Prescription:

Huperzine A 50mg

Mannitol 5g

Polyethylene glycol 6000 10g

Poloxamer 5g

Make 1000

Method for making: the micronizing of learning from else's experience is crossed the huperzine A of 200 mesh sieves and the mixing fine powders of mannitol is added in fused polyethylene glycol 6000 and the poloxamer mixed-matrix, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.

Six, example 6

Prescription:

Huperzine A 50mg

Mannitol 5g

Polyethylene glycol 6000 10g

Macrogol 4000 5g

Poloxamer 1g

Make 1000

Method for making: the micronizing of learning from else's experience is crossed the huperzine A of 200 mesh sieves and the mixing fine powders of mannitol is added in fused polyethylene glycol 6000, Macrogol 4000 and the poloxamer mixed-matrix, stirring evenly, is coolant with the dimethicone, the dropping preparation method pill, drying, promptly.

Claims (5)

1. huperzine dropping pills and preparation method thereof is characterized in that: 1 weight portion huperzine A and 50～200 weight portion carriers are added in 1～10 weight portion molten matrix through the mixing fine powders of micronizing, fully mixing, dropping preparation method is condensed into ball in coolant, remove coolant, drying, promptly.

2. the molecular formula of the described huperzine A of claim 1 is C ₁₅H ₁₈N ₂O, molecular weight are 242.32, and structural formula is

3. the described carrier of claim 1 includes but not limited to mannitol, lactose, sorbitol, xylitol, sucrose, fructose, glucose, maltose, aminoacid etc.

4. the described substrate of claim 1 includes but not limited to polyethylene glycol 6000, Macrogol 4000, polyethylene glycol 1500, cetomacrogol 1000, sodium stearate, glycerin gelatine, poloxamer, stearic acid, glycerol monostearate acid, insect wax etc.

5. the described coolant of claim 1 includes but not limited to dimethicone, liquid paraffin, vegetable oil, water, alcoholic solution etc.