CN1493275A - Paeonol drip pill and its preparation method - Google Patents

Abstract

A dripping pill of paeonal and its preparing process are disclosed. Its advantages are high dissolving and disintegrating speed, high stripping percentage, quickly taking its curative effect and low cost.

Description

Drop pills of paeonol and preparation method thereof

Technical field

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

Background technology

Paeonol is an analgesic.Result of study shows that the mouse writhing significant reaction that paeonol causes acetic acid reduces, and obviously improves the mice threshold of pain, obviously reduces the mice rectal temperature, and cooling effect has dose dependent, and reaches the peak at 0.5 hour, and temperature recovery is normal in 1-2 hour.The intravenous injection of typhoid fever bacterium causes the mice heating, and oral paeonol has the trivial solution heat effect, reaches the peak in 0.5 hour, continues 3 hours, and cooling effect is obvious.Generate heat due to mice three vaccines, paeonol also has antagonism.Paeonol is to by rat paw edema due to carrageenin, Ovum Gallus domesticus album, formaldehyde, histamine, 5-hydroxy tryptamine and the Kallidin I, the auricular concha swelling of xylol induced mice and endotoxin abdominal cavity capillary permeability raise all significant inhibitory effect, win rat bilateral adrenal gland after its antiinflammatory action still exist.The ascorbic content of rat adrenal gland is not had obvious influence, can not suppress by the compensatory hypertrophy of offside adrenal gland due to the one-sided excision rat adrenal gland.Its antiinflammatory action does not rely on hypophysis-adrenal system, does not have the effect of cortisone sample yet.Paeonol suppresses PGE in the inflammatory tissue ₂Biosynthesis, suppressing carrageenin pleuritis polymorphonuclear leukocyte divides a word with a hyphen at the end of a line, endotoxin abdominal cavity capillary permeability raises and the lipoxygenase activity is all had significant inhibitory effect, and paeonol can also prevent the mice stress ulcer and suppress the rat gastric secretion, and certain spasmolysis is arranged.Its antiinflammatory characteristics are different from NSAID (non-steroidal anti-inflammatory drug).Animal experiment shows that paeonol was pressed 75～100mg/kg lumbar injection continuous 5 days, significantly suppresses the reaction of Cavia porcellus Forssman cutaneous vasculitis, the reverse skin allergy of rat, rat active and passive Arthus type pedal swelling.Every day, 50～200mg/kg lumbar injection was to sheep red blood cell, the inductive mice delayed of bovine serum albumin pedal swelling, to 2, the mice contact dermatitis that the 4-dinitrofluorobenzene causes all has the obvious suppression effect, promptly II, III and IV allergic reaction type is all had inhibitory action.

The paeonol oral absorption is used ¹⁴C labelling paeonol experimental results show that rat oral gavage 16.6mg/kg, and concentration reaches top level in 20 minutes bleeding from anus, descends rapidly then, and administration distributes the highest with liver after 3 hours, be followed successively by kidney, spleen and lung.In the administration 24 hours in the urine and in the excrement elimination factor be respectively 89% and 5%, from urine, detect paeonol and metabolite 2 thereof, 4-dihydroxy acetophenone, 2,5-dihydroxy-3 kinds of materials of 4-methoxyacetophenone account for 11.4%, 21.0%, 67.6% respectively.Confirm the oral absorption rapidly of paeonol, metabolism and drainage.

List marketing at present have only paeonol coated tablet, clinical heating, headache, neuralgia, myalgia, rheumatic arthritis and the rheumatoid arthritis of being used for.

Paeonol has special smelly, and it is little peppery to distinguish the flavor of, insoluble in water, the disintegrate of paeonol coated tablet is slower, and dissolution and dissolution rate are lower, less stable, child, old people, sickbed patients or dysphagia patients are taken inconvenience, and compliance is relatively poor, have influenced the performance of paeonol therapeutical effect.

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

Summary of the invention

The drop pills of paeonol 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, bed patient, old people and dysphagia patients are taken, but also has working condition and production equipment is simple, production cost is low, and the advantage that supplementary product consumption reduces 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: the paeonol fine powder of 1 weight portion through micronizing is added in 1～10 weight portion molten matrix, abundant mixing, dropping preparation method is condensed into ball in coolant, remove coolant, drying, promptly.

The chemical name of paeonol is 2-hydroxyl-4-methoxyl group-1-Phenylethanone. among the present invention, and molecular formula is C ₉H ₁₀O ₃, molecular weight is 166.18, structural formula is:

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 first methods of Chinese Pharmacopoeia version in 2000), is a solvent with water 900ml, Revolution Per Minute 100 changes, operation in the time of 5,10,20,30 and 45 minutes, is got solution 10ml in accordance with the law, filter, it is an amount of that precision is measured subsequent filtrate, and thin up is made the solution that contains paeonol 6 μ g among every 1ml, measures according to spectrophotography (two appendix IV of Chinese Pharmacopoeia version in 2000 A), wavelength place at 275nm measures trap, presses C ₉H ₁₀O ₃Absorptance (E _1cm ^1%) be 862 calculating stripping quantities.

Two, commercially available paeonol sheet testing result

1. disintegration time: 51 minutes

2. dissolution rate:

Time (minute) 5 10 20 30 45

Dissolution (%) 21.2 32.3 52.5 61.3 72.5

Three, example 1 sample detection result

1. the molten diffusing time: 8 minutes

2. dissolution rate:

Time (minute) 5 10 20 30 45

Dissolution (%) 54.6 88.3 99.2 99.5 98.4

Four, example 2 sample detection results

1. the molten diffusing time: 10 minutes

2. dissolution rate:

Time (minute) 5 10 20 30 45

Dissolution (%) 51.18 5.2 98.3 99.6 99.7

Five, example 3 sample detection results

1. the molten diffusing time: 7 minutes

2. dissolution rate:

Time (minute) 5 10 20 30 45

Dissolution (%) 53.5 84.2 98.6 97.3 99.2

Six, example 4 sample detection results

1. the molten diffusing time: 10 minutes

2. dissolution rate:

Time (minute) 5 10 20 30 45

Dissolution (%) 51.3 85.3 98.6 98.9 99.2

Seven, example 5 sample detection results

1. the molten diffusing time: 12 minutes

2. dissolution rate:

Time (minute) 5 10 20 30 45

Dissolution (%) 45.6 78.5 86.2 99.2 100.1

Eight, example 6 sample detection results

1. the molten diffusing time: 16 minutes

2. dissolution rate

Time (minute) 5 10 20 30 45

Dissolution (%) 41.3 62.4 89.5 98.6 99.7

The specific embodiment

One, example 1

Prescription:

Paeonol 5g

Polyethylene glycol 6000 15g

Make 1000

Method for making: the paeonol fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves 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:

Paeonol 5g

Macrogol 4000 15g

Make 1000

Method for making: the paeonol fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves 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:

Paeonol 5g

Polyethylene glycol 6000 5g

Macrogol 4000 10g

Make 1000

Method for making: the paeonol fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in fused Macrogol 4000 and the polyethylene glycol 6000 mixed-matrix, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.

Four, example 4

Prescription:

Paeonol 5g

Glyceryl monostearate 15g

Make 1000

Method for making: the paeonol fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves 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:

Paeonol 5g

Polyethylene glycol 6000 10g

Poloxamer 5g

Make 1000

Method for making: the paeonol fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves 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:

Paeonol 5g

Glyceryl monostearate 15g

Poloxamer 1g

Make 1000

Method for making: get the mixing fine powders that paeonol and poloxamer cross 200 mesh sieves through micronizing and be added in the fused glyceryl monostearate substrate, mixing is a coolant with the frozen water, the dropping preparation method pill, and drying, promptly.

Claims (4)

1. drop pills of paeonol and preparation method thereof is characterized in that: the paeonol fine powder of 1 weight portion through micronizing is added in 1～10 weight portion molten matrix, and abundant mixing, dropping preparation method is condensed into ball in coolant, remove coolant, drying, promptly.

2. the chemical name of the described paeonol of claim 1 is 2-hydroxyl-4-methoxyl group-1-Phenylethanone., and molecular formula is C ₉H ₁₀O ₃, molecular weight is 166.18, structural formula is

3. 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.

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