CN1264516C - Ligustrazine phosphate dripping pill and preparation thereof - Google Patents
Ligustrazine phosphate dripping pill and preparation thereof Download PDFInfo
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- CN1264516C CN1264516C CN 03149886 CN03149886A CN1264516C CN 1264516 C CN1264516 C CN 1264516C CN 03149886 CN03149886 CN 03149886 CN 03149886 A CN03149886 A CN 03149886A CN 1264516 C CN1264516 C CN 1264516C
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Abstract
The present invention relates to a therapy medicine and a preparation method for treating the diseases of obliterative vascular disease, cerebral thrombosis, angitis, coronary artery disease, angina, etc. The present invention aims to make up for the deficiency of the prior art, provide a ligustrazine dripping pill having the advantages of high bioavailability, fast medicine effect release, obvious effect and convenience for using and carrying without toxic or side effect and also provide a preparation method of the ligustrazine dripping pill. Ligustrazine phosphate is used as raw materials which are proportionally added to the substrates of polyethylene glycol 6000, etc. as surface active agents, and then, the materials are uniformly mixed; the mixed materials are heated to a melting state and then put in a pill dropping machine after being uniformly stirred, and the mixed materials are dropped in condensed liquid at a proper speed to form the therapy medicine.
Description
[technical field] the present invention relates to a kind of medicine for the treatment of diseases such as obliterative vascular disease, cerebral thrombosis, vasculitis, coronary heart disease, angina pectoris and preparation method thereof.
[background technology] ligustrazine is one of composition of samphire Rhizoma Chuanxiong, now is artificial sintetics.Its hydrochlorate commonly used or phosphate because its phosphate is comparatively stable, are difficult for distillation, and the preparation oral solid formulation more has superiority than hydrochlorate, and this product has the effect of antiplatelet aggregation, and accumulative platelet is had the poly-effect of knot; Still can expand small artery, microcirculation improvement and cerebral blood flow produce antithrombotic and form and the thrombus dissolving effect.Be applicable to obliterative vascular disease, cerebral thrombosis, vasculitis, coronary heart disease, angina pectoris etc.To convalescent period acute stage and the sequela thereof of ischemic cerebrovascular, as cerebral blood supply insufficiency, cerebral thrombosis, cerebral embolism, cerebral arteriosclerosis etc.
According to another relevant report, ligustrazine is because of having the effect of calcium antagonist sample, and its novel clinical use is constantly extended:
1. acupoint injection therapy treatment coronary heart disease: get the back GEYU acupoint 4 milliliters of medicinal liquids are entered 2～3 centimetres of injections again in the inserting needle tailing edge spinal column direction of bringing about the desired sensation, every day 1 time, logotype 10 days not only can obviously improve patient's subjective symptoms, and cardiac function and hemorheology index are also obviously progressive.
2. drug treatment obstruction of fallopian tube in the uterine cavity: but the administration promoting blood circulation and detumescence improves local microcirculation in the direct uterine cavity of ligustrazine, promotes the spot adhesion to absorb and logical again fallopian tube.Method is 500 milligrams and adds 10 milliliters of normal saline, with double lumen tube medicinal liquid slowly injected the cavity of uterus fallopian tube of flowing through, administration in 3～7 days after menolipsis, 3 days 1 time, totally 3 times, menstruation drug withdrawal in preceding 15 days.1 the course of treatment recanalization rate reach 66%, 2 the course of treatment recanalization rate reach 88%.
3. knee joint osseous arthritis: patient's joint capsule and synovial membrane intravenous all have RCO, and the microcirculation stasis of blood stagnates, and makes cartilage degeneration, and this agent can resist above-mentioned pathological changes.Can inject 4 milliliters of medicinal liquids after most hydrarthrosis is taken out in the routine puncture, 1 time weekly, 6 times was 1 course of treatment, effective percentage 90%.
4. pain relieving: utilize maincenter calmness, the calcium antagonism of this agent, each 40 milligrams of intramuscular injection are to the acute abdominal pain effective percentage 83.8% that acute gastroenteritis, Peptic Ulcers, primary dysmenorrhea etc. cause, renal colic effective percentage 90%.
5. interstitial pulmonary fibrosis: heavy dose of ligustrazine can improve alveolar and interstitial lung blood circulation, removes blood capillary and bronchospasm, reduces the part and oozes out, and reduces pulmonary hypertension, thereby improves pulmonary function.Add in 500 milliliters of liquid quiet with 1.0 grams, every day 1 time, 20 times was 1 course of treatment, and positive effect is promptly arranged 2～3 courses of treatment.The result shows that this medicine improves SARS patient's pulmonary function and has meaning.
6. infantile asthma and bronchopneumonia: on the basis of routine treatment, add with quiet of 3～5 milligrams/per kilogram of body weight of this product every day 1 time, relief of symptoms rapidly, the shortening course of disease.
7. viral hepatitis: quiet 200 milligrams of every days, to the liver function of improving the patient, shorten the course of disease significant curative effect is arranged.General 3 weeks were 1 course of treatment.
8. tissue adhesion intestinal obstruction; Method is 100 milligrams and adds in 250 milliliters of liquid quiet, 25 milligrams of intramuscular injection chlorpromazine, and one repeats with 2 times, and medication on the one alleviation alleviated 88% in 66%, 3 day.
9. kidney disease: to acute and chronic nephritis, nephropathy, chronic kidney hypofunction and diabetes renal damage, on the basis of conventional therapy, add and use this agent, quiet 160～200 milligrams of every days (diabetic nephropathy is with 400～1000 milligrams), 14 days is 1 course of treatment, after 2 courses of treatment to bringing high blood pressure down, increase the urine amount, improving renal function and the blood biochemical metabolic index all has better effects.
Therefore ligustrazine has curative effect preferably to above-mentioned multiple disease, is a kind of medicine that is worth further research and development to utilize.Relevant reference material is as follows:
[1] Wang Tiancheng etc. ligustrazine is to the preventive effect of Ischemia and Reperfusion in vivo in Rats arrhythmia. Chinese gerontology magazine 1998,18:240-241
[2] Qin Xiaochen etc. ligustrazine is to rat myocardial ischemia and reperfusion injury protection experimental study of effect. the Henan traditional Chinese medical science 1997,17 (5): 274-276
[3] Wang Hui. ligustrazine is to the protective effect of heart and brain under the acute anoxia state. Chinese Pharmacological circular 2000,16 (6): 654-656
[4] Kong Xuli etc., ligustrazine are to the influence of cardiac muscle and coronary artery machinery electrical activity. CHINA JOURNAL OF CHINESE MATERIA MEDICA, 1998,23 (8): 491-493,512
[5] Dai Lingjuan etc. the discussion of ligustrazine treatment pulmonary fibrosis mechanism. the doctor studies magazine 1999,22 (11): 24-25
[6] Chen Liping etc. interferon, ligustrazine acupoint injection therapy treatment chronic active hepatitis B 48 examples. the time precious traditional Chinese medicines research 1995; 6 (2): 10
[7] horse great waves etc. ligustrazine suppresses the experimentation of platelet activation in the extracorporeal circulation. Suzhou Medical College journal 1995; 15 (1): 9
The ligustrazine preparation that utilizes prior art to obtain, commonly used have injection, transfusion and a tablet etc.
Ligustrazine injection and transfusion, untoward reaction is less and slight, and idol has stomach discomfort, xerostomia, drowsiness etc., cerebral hemorrhage and have bleeding tendency person to avoid usefulness.It is big simultaneously yet to exist operation easier, the shortcoming that the patient suffering is also big.
The ligustrazine tablet of clinical use, because the influence of first pass effect, bioavailability only 10～30%, compare onset simultaneously with injection also slower.
[summary of the invention] purpose of the present invention is to remedy the deficiencies in the prior art, and a kind of bioavailability height is provided, release fast, and produce effects is nontoxic fast, has no side effect, and uses ligustrazine drop easy to carry and preparation method thereof.
Can take following method to obtain ligustrazine drop involved in the present invention.
With the ligustrazine phosphate is primary raw material, according to certain ratio, adds surfactant polyethylene
6000Form etc. the substrate configuration.Specific as follows:
(1) prescription: ligustrazine phosphate substrate
Chinese name: ligustrazine phosphate, formal product 2 phosphate by name
Substrate: Polyethylene Glycol
6000, Polyethylene Glycol
4000, Polyethylene Glycol
1000, in the material such as stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers any one or a few mix mutually.
The ratio of ligustrazine phosphate and substrate is 1: 1～8
(2) preparation technology: concrete implementation step is as follows:
The first step is promptly got a ligustrazine phosphate raw material according to 1: 1～8 ratio, mixes with 1 part to 8 parts matrix phase; Substrate can be Polyethylene Glycol
6000, Polyethylene Glycol
4000, Polyethylene Glycol
10000, in the substrate such as stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers any one or a few mix mutually.
Second step was adopted water-bath, oil bath or other mode of heating, and mixed material is heated to fusion, stirred;
The 3rd step was inserted special-purpose drop pill machine, and as the DW-35 type drop pill machine of Taixing, Jiangsu second pharmaceutical machine factory production or the full-automatic Chinese medicine dripping pills machine of WD8-1 type of Tianjin machine tool plant of Hebei University of Technology production, keeping temperature is 60～95 ℃.
The 4th step was selected sizeable drip nozzle, with suitable speed, splashed in 40～-15 ℃ the condensing agent; Condensing agent can be any one or a few mixture in liquid paraffin, methyl-silicone oil, the vegetable oil.
The 5th step type to be shrunk to takes out, and removes the surface condensation agent, drying, and packing, promptly.
[beneficial effect] ligustrazine is one of composition of samphire Rhizoma Chuanxiong, and is existing with the synthetic product.This product has antiplatelet aggregation, expansion small artery, and microcirculation improvement and cerebral blood flow produce antithrombotic and form and the thrombus dissolving effect.Be applicable to obliterative vascular disease, convalescent period acute stage and the sequela of cerebral thrombosis, vasculitis, coronary heart disease, angina pectoris, ischemic cerebrovascular, as cerebral blood supply insufficiency, cerebral thrombosis, cerebral embolism, cerebral arteriosclerosis etc.
At present, the oral formulations such as ligustrazine tablet that utilize prior art to obtain, oral administration biaavailability is low, onset is slower, though untoward reaction is lighter, still has gastrointestinal irritation, xerostomia, side effect such as drowsiness.Injection and infusion solutions have acute toxic reaction or anaphylaxis report, also have shortcomings such as easily causing local pain when using inconvenience, injection simultaneously.The ligustrazine tablet, because the influence of first pass effect, bioavailability only 10～30%, onset is slower.
Pharmaceutical preparation involved in the present invention; utilize substrate such as surfactant polyethylene and ligustrazine phosphate crude drug to make solid dispersion; making medicine be molecule, colloid or microcrystalline state is scattered in the substrate; the total surface area of medicine increases; and substrate is hydrophilic; medicine is had wetting action, can make that medicine is rapidly molten to loose into microgranule or solution, thereby make the dissolving of medicine and absorb and accelerate.Thereby improved bioavailability, brought into play efficient, quick-acting effects etc.
Compare with tradition administering modes such as " tablet, capsule, injection ", exist essential distinction.Drop pill with the solid dispersion technology preparation can make effective ingredient fully contact with mucomembranous surface, absorbs by mucomembranous epithelial cell, directly enters blood circulation.Owing to directly enter blood circulation without liver, avoided first pass effect effectively, thereby it is rapid to have had curative effect, the bioavailability height, side effect is little, characteristics such as medication convenience.
1. compare with injection, avoided medicine and solvent thereof and adjuvant directly to enter sanguimotor process, can reduce acute toxic and side effects effectively and take place, safe in utilization, effect is lasting, applied range.
2. compare with oral tablet or capsule, this preparation not only can be oral, but sublingual administration still, this just overcome oral formulations onsets such as tablet, capsule slowly, shortcoming such as low, the gastrointestinal irritation of liver sausage first pass effect, bioavailability.
3. this dropping pill formulation volume is little, in light weight, more is applicable to and carries.After containing entrance cavity, contact promptly with saliva and to dissolve rapidly, and absorb by oral mucosa, not only rapid-action, and the influence of not taken food, promptly all can containing take after meal ante cibum.
4. the contained drug dose of each drop pill of this preparation is accurate, and the patient who is suitable for various disease, the different state of an illness, all ages and classes grasps dosage more accurately, can avoid the shortcoming of at every turn taking misty ideas such as half sheet or quarter-wave plate of tablet effectively.
5. the production technology for preparing this preparation-drop pill: equipment is simple, easy to operate; Operation is few, with short production cycle, automaticity is high, labor intensity is low, production efficiency is high; Workshop does not have dust, helps labor protection; The preparation drop pill need adopt high-tech means and equipment, and principal agent is uniformly dispersed in substrate, and dosage is accurate, and the ball method of double differences is different little than tablet; Production cost is lower than with below 50% of kind tablet.
6. this preparation is by after the heating of solid drugs and substrate, being melt into liquid state, splashes into to make in the not miscible condensed fluid.Therefore, the stability of drug height, not facile hydrolysis, oxidation, and the operation be under liquid state, to carry out, no dust pollution is not subject to the influence of crystal formation, thereby has guaranteed the quality of medicine.After being dissolved in substrate for easy oxidation or volatile medicine, can increase its stability, cover disagreeable taste.
In sum, make this preparation have the advantage of triple effect (quick-acting, efficient, long-acting), three little (taking dose is little, toxicity is little, side effect little), five convenience (convenient for production, store convenience, convenient transportation, easy to carry, easy to use).
The preparation technology of the ligustrazine drop that [preferred forms] is involved in the present invention, preferred forms is as follows;
The first step is promptly got a ligustrazine phosphate raw material, with 2.8 parts of Polyethylene Glycol according to 1: 2.8 ratio
4000Mix mutually;
Second step was heated to fusion with mixed material and stirred;
The 3rd step was inserted special-purpose drop pill machine, the full-automatic Chinese medicine dripping pills machine of WD8-1 type that DW-35 type drop pill machine of producing as Taixing, the Jiangsu second pharmaceutical machine factory or Tianjin machine tool plant of Hebei University of Technology produce, and keeping temperature is (85 ± 2) ℃;
The 4th step was selected sizeable drip nozzle, with suitable speed, splashed in 20～-5 ℃ the methyl-silicone oil.
The 5th step type to be shrunk to takes out, and removes the surface condensation agent, drying, and packing, promptly.
[example]
The experiment of example one ligustrazine phosphate and the different proportionings of substrate
Experimental design: for the different proportionings of observing primary raw material and substrate influence, be raw material, select Polyethylene Glycol with the ligustrazine phosphate to product involved in the present invention
4000Be substrate, respectively with 1: 1; 1: 2; 1: 3; 1: 4; 1: 5; 1: 6; 1: 7; 1: 8 ratio can obtain the experiment of eight different proportionings with ligustrazine phosphate and substrate mix homogeneously; Other promptly adopts water-bath that mixed raw materials is heated to molten condition respectively all according to the given condition in [optimum implementation], selects self-control drop pill machine, regulates its water dropper temperature and makes and remain on 85 ± 2 ℃; Select methyl-silicone oil as condensing agent, the refrigeration control system of regulating the drop pill machine makes the temperature of condensing agent remain on 0～20 ℃, and the step according to the previous process defined is prepared again, and experimental result sees Table one:
The experiment of table one ligustrazine phosphate and the different proportionings of substrate
| Ligustrazine: substrate | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| 1∶1 | 50.0 | 80 | ＜30 | ＞10 | + |
| 1∶2 | 33.3 | 86 | ＜30 | ＜10 | ++ |
| 1∶3 | 25.0 | 95 | ＜30 | ＜10 | +++ |
| 1∶4 | 20.0 | 95 | ＜30 | ＜10 | +++ |
| 1∶5 | 16.7 | 94 | ＜30 | ＜10 | +++ |
| 1∶6 | 14.3 | 94 | ＜30 | ＜10 | +++ |
| 1∶7 | 12.5 | 93 | ＜30 | ＜10 | +++ |
| 1∶8 | 11.1 | 92 | ＜30 | ＜10 | +++ |
* the hardness method for expressing adopts drop pill is placed on the glass plate, press...withes one's finger it, observes its metamorphosis."+" expression flicking promptly is out of shape, " ++ " expression distortion of firmly pressing, and " +++" expression is indeformable by it.
* the result by table one can find out: when the proportioning of ligustrazine phosphate and substrate reaches 1: 2 when above, the rounding rate, the ball method of double differences is different and index such as hardness, all can reach index preferably, continues to improve proportioning, and is little to above index influence.
Example diphosphonic acid ligustrazine and the mutually blended experiment of different substrates
Experimental design: mix influence mutually in order to observe primary raw material and different substrates, respectively with Polyethylene Glycol to product involved in the present invention
4000, Polyethylene Glycol
6000, Polyethylene Glycol
10000, ten kinds of different substrates such as stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers mix mutually with ligustrazine phosphate, mixed proportion is 1: 2.8, can obtain the experiment of ten different substrates; Other is all according to the given condition in [optimum implementation], be about to the raw material substrate different mix homogeneously respectively with each, adopt that water-bath is former with each mixings, adjuvant is heated to molten condition respectively and makes the drop pill machine by oneself, regulate its water dropper temperature and make and remain on 85 ± 2 ℃; With the methyl-silicone oil is condensing agent, and the refrigeration control system of regulating the drop pill machine makes the temperature of condensing agent remain on 0～20 ℃, and the step according to the previous process defined is prepared again, and experimental result sees Table two:
Table diphosphonic acid ligustrazine and the mutually blended experiment of different substrates
| The substrate title | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Polyethylene Glycol 4000 | 26.3 | 95 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 6000 | 26.3 | 96 | ＜30 | ＜10 | +++ |
| Polyethylene Glycol 10000 | 26.3 | 96 | ＜30 | ＜10 | +++ |
| Stearic acid | 26.3 | 50 | ＜30 | ＞10 | + |
| Sodium stearate | 26.3 | 54 | ＜30 | ＞10 | + |
| Glycerin gelatine | 26.3 | 61 | ＜30 | ＞10 | + |
| Glyceryl monostearate | 26.3 | 58 | ＜30 | ＞10 | + |
| Lac | 26.3 | 55 | ＜30 | ＞10 | - |
| The polyoxyethylene monostearate | 26.3 | 88 | ＜30 | ＜10 | ++ |
| Polyethers | 26.3 | 91 | ＜30 | ＜10 | ++ |
* the hardness method for expressing adopts drop pill is placed on the glass plate, press...withes one's finger it, observes its metamorphosis."+" expression flicking promptly is out of shape, " ++ " expression distortion of firmly pressing, and " +++" expression is indeformable by it.
* the result by table two can find out: when ligustrazine phosphate mixes mutually with different substrates, with Polyethylene Glycol
4000, Polyethylene Glycol
6000, Polyethylene Glycol
10000, polyoxyethylene monostearate, polyethers be for well, the rounding rate, the ball method of double differences is different and index such as hardness, all can reach index preferably, other several difference by comparison are bigger.
Select the experiment of different water dropper temperature in example three preparation process
Experimental design: in order to observe of the influence of the different water dropper temperature of selection in the preparation process, select self-control drop pill machine, regulate its water dropper temperature and make and remain on 60 ± 2 ℃ respectively product involved in the present invention, 70 ± 2 ℃, 80 ± 2 ℃, 90 ± 2 ℃, 95 ± 2 ℃; Can obtain five different experiments; Other is all according to the given condition in [optimum implementation], promptly with Polyethylene Glycol
4000For substrate is mixed mutually with ligustrazine phosphate, mixed proportion is 1: 2.8; With raw material and selected substrate mix homogeneously, adopt water-bath that mixed raw materials is heated to molten condition, with the methyl-silicone oil is condensing agent, the refrigeration control system of regulating the drop pill machine makes the temperature of condensing agent remain on 0～20 ℃, step according to the previous process defined is prepared again, and experimental result sees Table three:
Table three is selected the experiment of different condensing agents
| The water dropper temperature | Effective ingredient (%) | The rounding rate | Dissolve scattered time limit | The ball method of double differences is different | Hardness |
| (60±2)℃ | 26.3 | 58 | ＜30 | ＜10 | - |
| (70±2)℃ | 26.3 | 67 | ＜30 | ＜10 | + |
| (80±2)℃ | 26.3 | 80 | ＜30 | ＜10 | ++ |
| (90±2)℃ | 26.3 | 97 | ＜30 | ＜10 | +++ |
| (95±2)℃ | 26.3 | 95 | ＜30 | ＜10 | +++ |
* the hardness method for expressing adopts drop pill is placed on the glass plate, press...withes one's finger it, observes its metamorphosis."+" expression flicking promptly is out of shape, " ++ " expression distortion of firmly pressing, and " +++" expression is indeformable by it.
* the result by table three can find out: when the water dropper temperature of drop pill machine was more than (90 ± 2) ℃, the rounding rate, the ball method of double differences was different and index influence such as hardness is bigger, all can reach index preferably, was lower than the above index of this temperature range and obviously descended.
Select the experiment of different condensing agents in example four preparation process
Experimental design: select of the influence of different condensing agents in order to observe in the preparation process to product involved in the present invention, respectively with liquid paraffin, methyl-silicone oil, vegetable oil as condensing agent, can obtain three different experiments; Other is all according to the given condition in [optimum implementation], promptly with Polyethylene Glycol
4000Mix mutually with ligustrazine phosphate, mixed proportion is 1: 2.8, with raw material and substrate mix homogeneously, adopts heating in water bath to molten condition, selects self-control drop pill machine, regulates its water dropper temperature and makes and remain on 85 ± 2 ℃; The refrigeration control system of regulating the drop pill machine makes the temperature of condensing agent remain on 0～20 ℃, and the step according to the previous process defined is prepared again, and experimental result sees Table four:
Table four is selected the experiment of different condensing agents
| Condensing agent | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| Liquid paraffin | 26.3 | 90 | ＜30 | ＜10 | +++ |
| Methyl-silicone oil | 26.3 | 97 | ＜30 | ＜10 | +++ |
| Vegetable oil | 26.3 | 88 | ＜30 | ＜10 | +++ |
* the hardness method for expressing adopts drop pill is placed on the glass plate, press...withes one's finger it, observes its metamorphosis."+" expression flicking promptly is out of shape, " ++ " expression distortion of firmly pressing, and " +++" expression is indeformable by it.
* the result by table four can find out: select different condensing agents, and little to the influence of indexs such as the different and hardness of the ball method of double differences, just comparatively obvious to the influence of rounding rate index, be best with methyl-silicone oil.
Select the experiment of different condensing agent temperature in example five preparation process
Experimental design: select of the influence of different condensing agent temperature in the preparation process to product involved in the present invention in order to observe, regulate the refrigeration control system of drop pill machine, make the temperature of condensing agent remain on 20～-10 ℃ respectively, 30～-15 ℃, 40～-20 ℃, can obtain three different experiments; Other is all according to the given condition in [optimum implementation], promptly with Polyethylene Glycol
4000Mix mutually with ligustrazine phosphate, mixed proportion is 1: 2.8, with raw material and substrate mix homogeneously, adopts heating in water bath to molten condition, selects self-control drop pill machine, regulates its water dropper temperature and makes and remain on 85 ± 2 ℃; With the methyl-silicone oil is condensing agent, and the step according to the previous process defined is prepared again, and experimental result sees Table five:
Table five is selected the experiment of different condensing agent temperature
| The condensing agent temperature | Effective ingredient (%) | Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness |
| 20～-5℃ | 26.3 | 95 | ＜30 | ＜10 | +++ |
| 30～-10℃ | 26.3 | 92 | ＜30 | ＜10 | +++ |
| 40～-15℃ | 26.3 | 85 | ＜30 | ＜10 | +++ |
* the hardness method for expressing adopts drop pill is placed on the glass plate, press...withes one's finger it, observes its metamorphosis."+" expression flicking promptly is out of shape, " ++ " expression distortion of firmly pressing, and " +++" expression is indeformable by it.
* the result by table three can find out: when the temperature of condensing agent does not only have certain influence to the rounding rate index of finished product simultaneously, and index influence such as different and hardness is little to the ball method of double differences, is best with 20～-5 ℃.
Claims (2)
1. phosphoric ligustrazine drop is characterized in that: this drop pill is by ligustrazine phosphate and Polyethylene Glycol as substrate
6000Or Polyethylene Glycol
4000Uniform mixing forms, and the proportioning of ligustrazine and described substrate is counted 1: 2.8 with weight portion.
2. preparation method that is used for the described phosphoric ligustrazine drop of claim 1 is characterized in that being made of following step:
Step 1 is promptly got a ligustrazine phosphate raw material, with 2.8 parts Polyethylene Glycol according to 1: 2.8 ratio
6000Or Polyethylene Glycol
4000Mix mutually;
Step 2 adopts water-bath, oil bath or other mode of heating, and above-mentioned supplementary material is heated to fusion, stirs;
Step 3 is inserted the drop pill machine, and adjustment water dropper temperature is 85 ℃;
Step 4 is selected drip nozzle, with suitable speed, splashes in 20 ℃～-5 ℃ the methyl-silicone oil;
Step 5 type to be shrunk to takes out, and removes the surface condensation agent, drying, and packing, promptly.
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|---|---|---|---|
| CN 03149886 CN1264516C (en) | 2003-07-29 | 2003-07-29 | Ligustrazine phosphate dripping pill and preparation thereof |
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| CN1264516C true CN1264516C (en) | 2006-07-19 |
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| CN100348191C (en) * | 2005-11-07 | 2007-11-14 | 陈志成 | Gynostemma pentaphylla tolal glucoside dripping pills and its prepn. method |
| CN100423725C (en) * | 2006-09-04 | 2008-10-08 | 南昌弘益科技有限公司 | Production method of phosphoric ligustrazine drop |
| CN101544610B (en) * | 2008-03-24 | 2012-07-04 | 沈阳华泰药物研究有限公司 | Ligustrazine salt |
| CN101991614A (en) * | 2010-09-13 | 2011-03-30 | 吴赣英 | Compound fermented cordyceps sinensis powder (paecilomyces hepiali Cs-4 bacterial powder) combined medicine and preparation thereof |
| CN110585152A (en) * | 2019-10-23 | 2019-12-20 | 北京九发药业有限公司 | Large-size ligustrazine phosphate dropping pill |
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