CN101049311A - Compound Almitrine drop pills, and preparation technique - Google Patents
Compound Almitrine drop pills, and preparation technique Download PDFInfo
- Publication number
- CN101049311A CN101049311A CN 200610050160 CN200610050160A CN101049311A CN 101049311 A CN101049311 A CN 101049311A CN 200610050160 CN200610050160 CN 200610050160 CN 200610050160 A CN200610050160 A CN 200610050160A CN 101049311 A CN101049311 A CN 101049311A
- Authority
- CN
- China
- Prior art keywords
- almitrine
- drop pill
- raubasine
- bimesylate
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Abstract
A dripping pill of compound almitrine for treating subacute or chronic cerebrovascular insufficiency, cerebral apoplexy sequelae, senile dementia, dysmnesia, and ischemic cochleovestibular dysfunction is prepared from the almitrine bismesylate, raubasine and the matrix of dripping pill. Its preparing process is also disclosed.
Description
Technical field
The invention belongs to the pharmaceutical technology field, particularly a kind of by formulated compound almitrine drop pill of chemical raw material medicine almitrine bimesylate (Almitrine Bismesylate), raubasine (Raubasine) and drop pill substrate and preparation method thereof.
Background technology
Along with the arrival of world's aging society, numbers of patients such as senile hypomnesis, senile dementia are in rising trend in China, are after cardiovascular diseases, cerebrovascular and cancer, " the fourth-largest killer " of harm aged health.A large amount of research data both domestic and external shows that a senile dementia symptom of suffering from is in various degree just arranged among per ten old peoples.This has not only brought huge pressure for society, has also caused heavy financial burden, badly influences people's Health and Living quality.
The compound preparation of being made up of almitrine bimesylate and raubasine can be used for treating senile dementia and benign memory deficits etc., is antihypoxic, mainly by almitrine performance pharmacological action.Almitrine bimesylate, chemical name are 2, two (allyl the amino)-6-(4-(to fluorophenyl) methyl) of 4--1-piperazinyl-S-triazine dimethanesulfonate.Act on chemical receptor of carotid body, the excited breathing, thus the gas exchange of reinforcement alveolar-blood capillary increases art pO2 and blood oxygen saturation, increases the oxygen-supplying amount to cerebral tissue then, improves and promote brain function.Raubasine, chemistry are called (19 α)-16, the two dehydrogenations of 17--19-Jia Ji Evil yohimbane-16-carboxylate methyl ester.Be the brain metabolism improving medicine, can improve cerebrovascular insufficiency person's brain neuron mitochondria respiratoring control rate, microcirculation improvement, the action intensity and the effect that strengthen almitrine are held time.Both share, and brain cortex partial pressure of oxygen is increased, and increase brain tissue oxygen content, improve extraction and the utilization of cerebral tissue to glucose, recover aerobic metabolism, increase the energy supply of cell, thereby brain function is improved and strengthen.Be mainly used in subacute and chronic cerebrovascular insufficiency, apoplexy sequela, senile light, moderate dementia and benign memory deficits and the imbalance of ischemic cochlea vestibular function etc. clinically.
The compound almitrine oral formulations of using clinically is mainly tablet at present.Because conventional tablet fabricating technology and dosage form have, and make this class oral formulations exist disintegration time long, absorption difference, shortcomings such as onset is slow, and bioavailability is lower, thus giving full play to of drug effect influenced, between the storage life, be easy to sliver, variable color, the moisture absorption etc., the quality instability.Also be difficult to simultaneously adapt to and swallow inconvenient patient.Compound almitrine drop pill bioavailability height of the present invention, disintegrate is molten loose fast, the dissolution height, steady quality, release fast, produce effects fast can sublingual administration, also can swallow, and is easy to carry and use.Preparation process of the present invention is simple, and workshop does not have dust, uses supplementary product kind few, and production process is short, and cost is low.
Summary of the invention
The present invention seeks to overcome the defective of prior art, for clinical treatment provides a kind of bioavailability height, disintegrate is molten looses soon, dissolution height, steady quality, release fast, quick produce effects, compound almitrine drop pill and preparation technology thereof easy to carry and use.
The invention is characterized in by medicinal chemicals almitrine bimesylate, raubasine and drop pill substrate formulated.The weight ratio of each composition is:
The two weight sum of almitrine bimesylate and raubasine: drop pill substrate=1: 1～1: 9
The weight ratio of two kinds of crude drug is:
Almitrine bimesylate: raubasine=3: 1
The present invention can be achieved through the following technical solutions:
Get almitrine bimesylate, raubasine, pulverize separately also sieves, almitrine bimesylate mixes by weight 3: 1 with raubasine, weight ratio by two kinds of crude drug weight sums and drop pill substrate is 1: 1～1: 9 mix homogeneously again, put and be heated to fusion in the heater while stirring, stir, the dropping preparation method pill, the water dropper temperature is 75 ℃-95 ℃, splashes in dimethicone or other drop pill coolant, and the temperature of coolant is 40 ℃--5 ℃, separate drop pill, absorb coolant, drying, promptly.
Utilize the drop pill of method preparation of the present invention, its beneficial effect is:
1. the quick stripping of medicine, the dissolution height, rapid-action, the bioavailability height, side effect is little.Almitrine bimesylate, raubasine are insoluble in water, and the absorption rate of medicine improves with the increase of dispersion.The compound almitrine drop pill is to adopt solid dispersion technology, will be in water behind the medicine and the fusion of drop pill substrate of indissoluble, make and quenching is solidified by dripping, and make medicine be molecule, colloid or microcrystalline state and be scattered in the substrate.Because the gross area of medicine increases, medicine disengages with crystallite or unformed microgranule, so the medicine dissolution quickening, helps absorption of human body, brings into play curative effect rapidly, improves bioavailability, reduces side effect.
2. increased administering mode, can swallow, but also sublingual administration.Sublingual administration has made things convenient for the patient of dysphagia for the patient of dysphagia provides a kind of new medication to select.As adopt the sublingual administration administration, and and after contacting, saliva dissolves rapidly, absorb by oral mucosa, directly enter blood circulation without gastrointestinal tract and liver, not only avoided the liver sausage first-pass effect, and it is rapid to have reached onset, improve bioavailability, reduce the purpose of side effect.
3. medicine stability is good.Dropping pill formulation by medicine and substrate heating and melting after, splash in the immiscible liquid coolant and make, reduce with the air contact area, be difficult for oxidation, substrate is non-water thing, is difficult for causing drug hydrolysis, stability of drug is increased, thereby guaranteed drug quality.
4. drop pill production technology, production equipment are simple, with short production cycle, the production efficiency height, and cost is low.
5. in the main production process of drop pill, used material all is to carry out under liquid state, has reduced dust pollution, helps labor protection and environmental protection, helps the GMP management.
The specific embodiment
One. the supplementary material medicine
Compound almitrine drop pill crude drug is almitrine bimesylate and raubasine.
The almitrine bimesylate chemical name is 2, two (allyl the amino)-6-(4-(to fluorophenyl) methyl) of 4--1-piperazinyl-S-triazine dimethanesulfonate.
Almitrine bimesylate molecular formula: C
26H
29F
2N
72CH
3SO
3H
Almitrine bimesylate molecular weight: 669.77
The raubasine chemical name is (19 α)-16, the two dehydrogenations of 17--19-Jia Ji Evil yohimbane-16-carboxylate methyl ester.
Raubasine molecular formula: C
21H
24N
2N
3
Raubasine molecular weight: 352.43
Adjuvant is drop pill substrate polyethylene glycols, carboxymethyl starch sodium, poloxamer, betacyclodextrin, stearic acid, sodium stearate, polyoxyethylene monostearate.
Two. preparation method
Get almitrine bimesylate, raubasine, pulverize separately also sieves, almitrine bimesylate and raubasine were by weight 3: 1 mix homogeneously, weight ratio by two kinds of crude drug weight sums and drop pill substrate is 1: 1～1: 9 mix homogeneously again, put and be heated to fusion in the heater while stirring, stir, the dropping preparation method pill, the water dropper temperature is 75 ℃-95 ℃, splashes in dimethicone or other drop pill coolant, and the temperature of coolant is 40 ℃--5 ℃, separate drop pill, absorb coolant, drying, promptly.
Three. specific embodiment
Further the present invention can be described by the following examples, but not limited by embodiment.
Embodiment 1: present embodiment is by almitrine bimesylate, raubasine and single-matrix prescription, operate according to the preparation method in (specific embodiment), coolant is a dimethicone, drip the system drop pill, select that roundness, the ball method of double differences are different, hardness, molten diffusing time etc. are index, observe the influence of the weight ratio of medicine and single-matrix to product involved in the present invention, result of the test sees Table 1.
Table 1 medicine and single-matrix formula test (medicine is 1 part)
Annotate: 1. coolant is a dimethicone, and chilling temperature is 3～5 ℃; Spice insulation and water dropper temperature are 85～90 ℃; Dripping speed is 30～50/minute.
2. above result shows, it is better to test every index 3,4,5,7,8,9, No. 10, and promptly medicine and substrate ratio are can drip system smoothly at 1: 2～1: 9 o'clock.But consider factors such as taking dose, optimum ratio is 3,4,8, No. 9 tests, and promptly medicine and substrate ratio are 1: 3～5.
Embodiment 2: present embodiment is by almitrine bimesylate, raubasine and mixed-matrix prescription, operate according to the preparation method in (specific embodiment), coolant is a dimethicone, drip the system drop pill, select that roundness, the ball method of double differences are different, hardness, molten diffusing time etc. are for investigating index, observe the influence of the weight ratio of medicine and mixed-matrix to product involved in the present invention, result of the test sees Table 2.
Table 2 medicine and mixed-matrix formula test (medicine is 1 part)
| 3 | Macrogol 4000: polyethylene glycol 6000=1: 3 (9 parts) | +++ | ＜10 | +++ | ＜15 | +++ |
| 4 | Polyethylene glycol 6000: carboxymethyl starch sodium=1: 0.3 (1 part) | ++ | ＜10 | +++ | ＜15 | ++ |
| 5 | Polyethylene glycol 6000: carboxymethyl starch sodium=1: 0.3 (3 parts) | +++ | ＜10 | +++ | ＜15 | +++ |
| 6 | Polyethylene glycol 6000: carboxymethyl starch sodium=1: 0.3 (9 parts) | +++ | ＜10 | +++ | ＜15 | +++ |
| 7 | Polyethylene glycol 6000: poloxamer=1: 0.2 (1 part) | +++ | ＜10 | ++ | ＜15 | ++ |
| 8 | Polyethylene glycol 6000: poloxamer=1: 0.2 (3 parts) | +++ | ＜10 | +++ | ＜15 | +++ |
| 9 | Polyethylene glycol 6000: poloxamer=1: 0.2 (9 parts) | +++ | ＜10 | +++ | ＜15 | +++ |
| 10 | Polyethylene glycol 6000: polyoxyethylene monostearate=1: 0.1 (1 part) | ++ | ＜10 | +++ | ＜15 | ++ |
| 11 | Polyethylene glycol 6000: polyoxyethylene monostearate=1: 0.1 (3 parts) | +++ | ＜10 | +++ | ＜15 | +++ |
| 12 | Polyethylene glycol 6000: polyoxyethylene monostearate=1: 0.1 (9 parts) | +++ | ＜10 | +++ | ＜15 | +++ |
Annotate: 1. coolant is a dimethicone, and chilling temperature is 8～5 ℃; Spice insulation and water dropper temperature are 85～90 ℃; Dripping speed is 30～50/minute.
2. above result shows, it is all better to test every index 2,3,5,6,8,9,11, No. 12, and promptly medicine and substrate ratio are can drip system smoothly at 1: 1～1: 9 o'clock.But consider factors such as taking dose, optimum ratio is 2,5,8, No. 11 tests, and promptly medicine and substrate ratio are 1: 3.
Embodiment 3: present embodiment is by selecting different coolants for use, and coolant is dimethicone, liquid paraffin, vegetable oil, and single-matrix is selected Polyethylene Glycol for use
6000, mixed-matrix is selected Polyethylene Glycol for use
6000: the prescription of poloxamer=1: 0.2, according to the preparation method in (specific embodiment) operation, drip the system drop pill, select that roundness, the ball method of double differences are different, hardness, molten diffusing time etc. are for investigating index, observe the influence of different coolants to product involved in the present invention, result of the test sees Table 3.
Table 3 is selected the test (medicine: substrate=1: 3) of different coolants for use
Annotate: 1. chilling temperature is 8～5 ℃; Spice insulation and water dropper temperature are 85～90 ℃; Dripping speed is 30～50/minute.
2. above result shows, it is better to test every index 1, No. 2, and when promptly selecting above-mentioned different coolant for use, comparatively preferred coolant is a dimethicone.
Embodiment 4: present embodiment is by selecting different coolant temperatures for use, and the temperature of coolant is respectively 35 ℃, and 25 ℃, 15 ℃, 5 ℃, 0 ℃ ,-5 ℃, temperature error ± 2 ℃, substrate is selected Polyethylene Glycol for use
6000,, be coolant with the dimethicone according to the operation of the preparation method in (specific embodiment), drip the system drop pill, select that roundness, the ball method of double differences are different, hardness, molten diffusing time etc. are for investigating index, observe the influence of different coolant temperatures to product involved in the present invention, result of the test sees Table 4.
Table 4 is selected the test (medicine: substrate=1: 3) of different coolant temperatures for use
Annotate: 1. spice insulation and water dropper temperature are 85～90 ℃; Dripping speed is 30～50/minute.
2. above result shows, it is better to test every index 3,4, No. 5, and when promptly selecting above-mentioned different coolant temperature for use, comparatively preferred coolant temperature is 15 ℃～0 ℃
Embodiment 5: present embodiment is by selecting different water dropper temperature for use, and the temperature of water dropper remains on 75 ℃ respectively, and 85 ℃, 95 ℃, temperature error＜3%, single-matrix is selected Polyethylene Glycol for use
6000, mixed-matrix is selected Polyethylene Glycol for use
6000: the prescription of poloxamer=1: 0.2, operate according to the preparation method in (specific embodiment), coolant is a dimethicone, drip the system drop pill, select that roundness, the ball method of double differences are different, hardness, molten diffusing time etc. are for investigating index, observe the influence of different water dropper temperature to product involved in the present invention, result of the test sees Table 5.
Table 5 is selected the test (medicine: substrate=1: 3) of different water dropper temperature for use
Annotate: 1. chilling temperature is 8～5 ℃; Dripping speed is 30～50/minute.
2. above result shows, it is better to test every index 3, No. 4, and when promptly selecting above-mentioned different water dropper temperature for use, comparatively preferred water dropper temperature is 85 ℃.
Claims (4)
1. compound almitrine drop pill and preparation technology thereof is characterized in that by medicinal chemicals almitrine bimesylate (Almitrine Bismesylate), raubasine (Raubasine) formulated with drop pill substrate.The weight ratio of each composition is:
The two weight sum of almitrine bimesylate and raubasine: drop pill substrate=1: 1～1: 9.
2. compound almitrine drop pill according to claim 1, its crude drug are the compound medicine composition, are made up of almitrine bimesylate, two kinds of medicines of raubasine.The weight ratio of two kinds of crude drug is:
Almitrine bimesylate: raubasine=3: 1
3. according to claim 1,2 described compound almitrine drop pill, it is characterized in that described drop pill substrate is a kind of or several compatibilities in polyethylene glycols, carboxymethyl starch sodium, poloxamer, betacyclodextrin, stearic acid, sodium stearate, the polyoxyethylene monostearate, the content of each compatibility composition all is not equal to zero.
4. according to claim 1,2 and 3 described compound almitrine drop pill, it is characterized in that preparation method is as follows:
Get almitrine bimesylate, raubasine, pulverize separately also sieves, almitrine bimesylate and raubasine were by weight 3: 1 mix homogeneously, weight ratio by two kinds of crude drug weight sums and drop pill substrate is 1: 1～1: 9 mix homogeneously again, put and be heated to fusion in the heater while stirring, stir, the dropping preparation method pill, the water dropper temperature is 75 ℃-95 ℃, splashes in dimethicone or other drop pill coolant, and the temperature of coolant is 40 ℃--5 ℃, separate drop pill, absorb coolant, drying, promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610050160 CN101049311A (en) | 2006-04-03 | 2006-04-03 | Compound Almitrine drop pills, and preparation technique |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610050160 CN101049311A (en) | 2006-04-03 | 2006-04-03 | Compound Almitrine drop pills, and preparation technique |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101049311A true CN101049311A (en) | 2007-10-10 |
Family
ID=38781047
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610050160 Pending CN101049311A (en) | 2006-04-03 | 2006-04-03 | Compound Almitrine drop pills, and preparation technique |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101049311A (en) |
-
2006
- 2006-04-03 CN CN 200610050160 patent/CN101049311A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1686342A (en) | Herminium drip pill and its preparation method | |
| CN101049311A (en) | Compound Almitrine drop pills, and preparation technique | |
| CN1686479A (en) | Loquat drip pill for treating cough and its preparation method | |
| CN1634509A (en) | Yitongshu drop pill for treating pain and its preparation method | |
| CN1301107C (en) | Xiyanping drop pills of possessing function of clearing away heat and toxic materia and preparation method | |
| CN1679669A (en) | Polygala dropping balls and preparation thereof | |
| CN1287771C (en) | Almond cough-relieving drop pills and preparation method thereof | |
| CN1679673A (en) | Isatis root drops and preparation thereof | |
| CN1307984C (en) | Cervix cancer drip pill and its preparation method | |
| CN1634452A (en) | Yin-nourishing lung-heat clearing drop pills | |
| CN101049309A (en) | Cinnarizine drop pills, and preparation method | |
| CN1679675A (en) | Chuanhuang anti-inflammation drops for clearing away heat and detoxicating, and preparation thereof | |
| CN1294902C (en) | Cough and asthma relieving drop pills prepared using dahurian rhododendron leaf | |
| CN1682818A (en) | Fleabane and earthworm dripping pill and its preparing method | |
| CN1301094C (en) | Throat pain relieving anti-inflammation drop pills for treating oral disease and preparation method thereof | |
| CN1634155A (en) | Propolis dripping pills for treating toothache and its preparation method | |
| CN1634490A (en) | Drop pills for treating throat diseases and preparation method thereof | |
| CN1562001A (en) | Carbazochrome sodium sulfoate dripping pill and its preparing method | |
| CN1709420A (en) | Motherwort dropping pill and its preparing method | |
| CN1698819A (en) | Schizandrol dripping pills for decreasing aminopherase and method for preparing the same | |
| CN1634477A (en) | Tendril-leaved fritillary bulb cough-relieving drop pills and preparation method thereof | |
| CN1679672A (en) | Rabdosia rubescens drops and preparation thereof | |
| CN1686129A (en) | Cepharanthine drip pill and its preparation method | |
| CN1709468A (en) | Pulmonary-toxin-clearing dropping pill using hop extract as raw material, and its preparing method | |
| CN1698797A (en) | Blood pressure lowering dripping pills with chryanthemum flower and pearl and its preparation process |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |