CN1686372A - Xiangdan emulsion for injection and its preparation method - Google Patents
Xiangdan emulsion for injection and its preparation method Download PDFInfo
- Publication number
- CN1686372A CN1686372A CN 200510059756 CN200510059756A CN1686372A CN 1686372 A CN1686372 A CN 1686372A CN 200510059756 CN200510059756 CN 200510059756 CN 200510059756 A CN200510059756 A CN 200510059756A CN 1686372 A CN1686372 A CN 1686372A
- Authority
- CN
- China
- Prior art keywords
- emulsion
- contain
- injection
- lignum dalbergiae
- dalbergiae odoriferae
- 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
Landscapes
- Medicinal Preparation (AREA)
Abstract
A nano-class or subnano-class Xiangdan emulsion for injection with high curative effect is disclosed, which is an improvement to existing Xiangtan injection.
Description
Technical field
The present invention relates to a kind of Xiangdan emulsion for injection, it contains Radix Salviae Miltiorrhizae extract, volatile oil of Lignum Dalbergiae Odoriferae, surfactant and water-bearing media, more specifically to the nanometer microemulsion type and the sub-nanometer emulsion type of these preparations.
Compare with commercially available fragrant red injection, Xiangdan emulsion for injection has that functional component is clear and definite, consumption is little, drug effect is remarkable and characteristics such as side effect is little.
Background technology
XIANGDAN ZHUSHEYE is made up of Radix Salviae Miltiorrhizae and Lignum Dalbergiae Odoriferae two flavor medical materials, has the effect of blood vessel dilating, enhancement coronary artery blood flow, is used for the treatment of angina pectoris, myocardial infarction.Traditional XIANGDAN ZHUSHEYE has only been used the water soluble ingredient of Radix Salviae Miltiorrhizae and the Aromatic water in the extraction volatile oil of Lignum Dalbergiae Odoriferae process, and from the result of modern pharmacological research, technology is very unreasonable, need to be improved and enhanced.
Radix Salviae Miltiorrhizae has good resisting coronary heart disease effect.Its effective ingredient mainly is danshensu (p-3,4 dihydroxy phenyl lactic acid) and TANSHINONES.The effective ingredient that is separated to from the salvia-soluble position---danshensu (danshensu), i.e. D (+) β-(3, the 4-dihydroxy phenyl) lactic acid, Chinese scholar has been carried out many pharmacological researches, proves that it has multiple pharmacologically active.Such as: have the effect of dwindling myocardial infarct size and alleviating the course of disease; has protective effect to the rat heart muscle ischemia/reperfusion injury; effect with microcirculation improvement obstacle and reduction blood plasma lactic acid content; have the microcirculation improvement obstructive action, thereby improve the dysbolismus due to the cell hypoxic-ischemic.Clinical practice finds that danshensu can increase blood capillary fragility, and long-term transfusion can cause endothelial denudation.
From Radix Salviae Miltiorrhizae, extract total tanshinone, have coronary artery dilator, coronary blood flow increasing; Decreased heart rate increases myocardial contraction, improves the myocardial metabolism disorder and the cardiac function that cause after the anoxia; Anticoagulant; Promote tissue repair and effect such as antibiotic, antibacterial.Can be used as the treatment of angina pectoris and myocardial infarction, cerebral arteries and arteria retina and the formation of peripheral vein thrombosis, Behcet's syndrome, erythema nodosum.
The Chinese medicine Lignum Dalbergiae Odoriferae is the dry duramen of leguminous plant Lignum Dalbergiae Odoriferae wingceltis trunk and root.Outside the source Lignum Dalbergiae Odoriferae wingceltis of its medical material, in the sissoo of using as Lignum Dalbergiae Odoriferae in addition among the people, India Lignum pterocarpi indici, Hainan yellow wingceltis, and the Lignum Dalbergiae Odoriferae commodity of external import.The Lignum Dalbergiae Odoriferae function is promoting the circulation of QI to relieve pain, promoting blood circulation and hemostasis.Be used for the vexed pain in ambition, the twinge of the gastral cavity side of body; The external treatment traumatic injury is hemorrhage.Existing chemical medicine reason studies show that volatile oil of Lignum Dalbergiae Odoriferae can suppress thrombosis.Lignum Dalbergiae Odoriferae can suppress the formation of the biosynthesis and the leukotriene of prostaglandin, and active ingredient is the yellow alkene of Lignum Dalbergiae Odoriferae wingceltis.In traditional XIANGDAN ZHUSHEYE, Lignum Dalbergiae Odoriferae extracts volatile oil through vapor distillation, but because volatile oil of Lignum Dalbergiae Odoriferae water solublity extreme difference has only adopted Aromatic water in the actual production, has abandoned or adopted oil reservoir, and effective ingredient is lost greatly.Waste medical material, increased production cost.
Xiangdan emulsion for injection of the present invention makes full use of volatile oil of Lignum Dalbergiae Odoriferae, TANSHINONES effective site, and traditional XIANGDAN ZHUSHEYE is made nanometer microemulsion type and inferior nano-emulsion novel form, and it is little to have a consumption, curative effect height, characteristics such as few side effects.
Summary of the invention
Along with going deep into of middle pharmaceutically active ingredient research, find that technology that XIANGDAN ZHUSHEYE adopts only extracted a kind of effective site danshensu of Radix Salviae Miltiorrhizae, carry most of volatile oil of Lignum Dalbergiae Odoriferae because water insolublely influenced the orange lightness of injection and be dropped.The present invention has also adopted nanometer microemulsion type or inferior nano-emulsion novel form, compares with traditional XIANGDAN ZHUSHEYE, has that functional component is clear and definite, consumption is little, curative effect is high and characteristics such as side effect is little.
Xiangdan emulsion for injection of the present invention, it contains Radix Salviae Miltiorrhizae extract, volatile oil of Lignum Dalbergiae Odoriferae, surfactant and water-bearing media.This injection is a kind of aqueous dispersion, the mean diameter of decentralized photo≤0.5 micron, and the concentration of extract is 0.01%～8% in the injection.Wherein contain TANSHINONES letones and salvianolic acid material in the Radix Salviae Miltiorrhizae extract.The content of the content of tanshinone material in liposoluble extract is 50-99.99%, and salvianolic acid class material content in water solubility extract is 50-99.99%; Volatile oil of Lignum Dalbergiae Odoriferae is through vapor distillation or CO
2Supercritical extraction is carried.
The liposoluble constituent of Radix Salviae Miltiorrhizae mostly is conjugation quinone, ketone compounds greatly, has the orange-yellow and orange red of feature.Mainly contain: Tanshinone I, tanshinone, TANSHINONES, cryptotanshinone, hydroxyl TANSHINONES, Methyl tanshinoate, methine Radix Salviae Miltiorrhizae quinone, Przewaquinone A Przewatanshinquinone A, Przewatanshinquinone B Przewaquinone B., penta element, miltirone, dihydro Radix Salviae Miltiorrhizae quinone, tanshinol, hydroxyl TANSHINONES, fall TANSHINONES, tetrahydrochysene Radix Salviae Miltiorrhizae quinone, iso tanshinone, different cryptotanshinone, Radix Salviae Miltiorrhizae quinone, dihydro miltirone, diterpene perinaphthenone, danshenspiroketallactone, salviol, Radix Salviae Miltiorrhizae aldehyde etc.
The water soluble ingredient of Radix Salviae Miltiorrhizae is mainly the salvianolic acid material, mainly contains saivianic acid A and also claims danshensu: dihydroxy benzenes lactic acid, danshensuan B, sahianic acid C, the acid of amber pool, salvianolic acid, salvianolic acid B, salvianolic acid F, sitosterol, ursolic acid protocatechualdehyde, the acid of Singapore coffee, Hesperetic acid, rosmarinic acid, rosmarinic acid methyl ester, ferruginal, tigogenin, carnosol etc.
Surfactant is selected from one or more in phospholipid (plant phospholipid, animal phospholipid, synthetic phospholipid), propylene glycol, fatty glyceride, solutolHS15, labrosol, Tweens, poloxamer series, polyoxyethylene fatty acid ester, Polyethylene Glycol and derivant series thereof, hydroxypropyl, the hydroxypropyl Υ-cyclodextrin;
Can also add triglyceride in the surfactant or as the glycerol of isotonic agent, wherein triglyceride comprises vegetable oil or medium chain triglyceride, can also add fatty acid or aliphatic alcohol or its sodium salt as co-emulsifier, cholic acid or deoxycholic acid and sodium salt thereof, wherein the carbon number that comprises of fatty acid or aliphatic alcohol can be from 6-24, antioxidant such as tocopherol (vitamin E) or L-ascorbyl palmitate can also be added, cosolvent ethanol can also be added.
Xiangdan emulsion for injection of the present invention, tanshinone material, volatile oil of Lignum Dalbergiae Odoriferae can be made nano-emulsion preparation or inferior nano-emulsion preparation separately, the salvianolic acid material is made liquid drugs injection, during administration with tanshinone emulsion with danshensu liquid drugs injection dilution posterior vein drop or inject; Also tanshinone material, volatile oil of Lignum Dalbergiae Odoriferae can be made the decentralized photo of Emulsion, during the salvianolic acid material is soluble in the aqueous phase, during administration with an amount of 0.9% sodium chloride solution or 5% glucose dilution posterior vein drop or inject.
Its preparation method is as follows:
A) tanshinone material, volatile oil of Lignum Dalbergiae Odoriferae are dissolved in triglyceride or the ethyl oleate, make oil phase in 50-90 ℃ of high-speed stirred, all the other components are dissolved in the suitable quantity of water, make water in 50-90 ℃ of high-speed stirred, the biphase 50-90 of being mixed in of a profit ℃ high-speed stirred is made primary emulsion, regulates pH value 5.0-7.0.
B) get primary emulsion in above-mentioned (a), water for injection adds to recipe quantity, is transferred in the high pressure dispersing emulsification machine emulsifying repeatedly.
To emulsion droplet mean diameter≤0.5 micron.
C) after the Emulsion of getting above-mentioned (b) filtered, inflated with nitrogen fill, sterilization were both.
Specific embodiment
Embodiment 1 (sub-nanometer emulsion type)
Prescription one: tanshinone material 0.001%-1.0%, salvianolic acid material 0.001%-1.0%, volatile oil of Lignum Dalbergiae Odoriferae 0.5%-5.0%, phosphatidase 10 .5%-4.0%, glycerol 1.0%-6.0%, triglyceride 5%-20%, oleic acid 1.0%-6.0%, tocopherol 0.01%-1.0%, water for injection add to 100%.
Take by weighing TANSHINONES (total tanshinone content 93%) 20mg and be dissolved in an amount of organic solvent, add volatile oil of Lignum Dalbergiae Odoriferae 1g, refined soybean oil or midchain oil 10g, oleic acid 4g, high-speed stirred makes mix homogeneously, removes organic solvent in 60 ℃ of distilling under reduced pressure, makes oil phase; Take by weighing salvianolic acid material (total tanshinone content 80%) 30mg, soybean phospholipid 2.2g, glycerol 3.6g, tocopherol 50mg, make abundant dispersion, make water in 60 ℃ of high-speed stirred.The biphase mixing of profit is made primary emulsion in 60 ℃ of-80 ℃ of high-speed stirred.Get primary emulsion, water for injection adds to recipe quantity, and regulating pH value is 5.0～7.0, is transferred in the high pressure dispersing emulsification machine, emulsifying is to emulsion droplet mean diameter≤0.5 micron repeatedly, and aseptic filtration, inflated with nitrogen fill, sterilization are both.
Prescription two: tanshinone material 0.001%-1.0%, salvianolic acid material 0.001%-1.0%, volatile oil of Lignum Dalbergiae Odoriferae 0.5%-5.0%, phosphatidase 10 .5%-4.0%, glycerol 1.0%-6.0%, triglyceride 5%-20%, oleic acid 1.0%-6.0%, tocopherol 0.01%-1.0%, PEG400/600 0.5%-5.0%, water for injection add to 100%.
Take by weighing TANSHINONES (total tanshinone content 93%) 20mg and be dissolved in an amount of organic solvent, add volatile oil of Lignum Dalbergiae Odoriferae 1g, refined soybean oil or midchain oil 10g, oleic acid 3.5g, high-speed stirred makes mix homogeneously, removes organic solvent in 60 ℃ of distilling under reduced pressure, makes oil phase; Take by weighing salvianolic acid material (total tanshinone content 80%) 30mg, soybean phospholipid 2.2g, glycerol 4g, tocopherol 50mg, ethylene glycol 400/600 0.5g and make abundant dispersion, make water in 60 ℃ of high-speed stirred.The biphase mixing of profit is made primary emulsion in 60 ℃ of high-speed stirred.Get primary emulsion, water for injection adds to recipe quantity, and regulating pH value is 5.0～7.0, goes in the high pressure dispersing emulsification machine, emulsifying is to emulsion droplet mean diameter≤0.5 micron repeatedly, and the fill of aseptic filtration inflated with nitrogen, sterilization are both.
Prescription three: tanshinone material 0.001%-1.0%, salvianolic acid material 0.001%-1.0%, volatile oil of Lignum Dalbergiae Odoriferae 0.5%-5.0%, phosphatidase 10 .5%-4.0%, solutolHS15 0.1%-3.0%, glycerol 1.0%-6.0%, triglyceride 5%-20%, oleic acid 1.0%-6.0%, tocopherol 0.01%-1.0%, water for injection add to 100%.
Take by weighing TANSHINONES (total tanshinone content 93%) 15mg and be dissolved in an amount of organic solvent, add volatile oil of Lignum Dalbergiae Odoriferae 1g, refined soybean oil or midchain oil 10g, oleic acid 3.5g, high-speed stirred makes mix homogeneously, removes organic solvent in 60 ℃ of distilling under reduced pressure, makes oil phase; Take by weighing salvianolic acid material (total tanshinone content 80%) 30mg, soybean phospholipid 1.5g, solutolHS150.5g, glycerol 3g, tocopherol 50mg and make abundant dispersion, make water in 60 ℃ of high-speed stirred.The biphase mixing of profit is made primary emulsion in 60 ℃ of high-speed stirred.Get primary emulsion, water for injection adds to recipe quantity, and regulating pH value is 5.0～7.0, is transferred in the high pressure dispersing emulsification machine, emulsifying is to emulsion droplet mean diameter≤0.5 micron repeatedly, and the fill of aseptic filtration inflated with nitrogen, sterilization are both.
Prescription four: tanshinone material 0.001%-1.0%, salvianolic acid material 0.001%-1.0%, volatile oil of Lignum Dalbergiae Odoriferae 0.5%-5.0%, phosphatidase 10 .5%-4.0%, solutolHS15 0.1%-3.0%, glycerol 1.0%-6.0%, triglyceride 5%-20%, oleic acid 1.0%-6.0%, tocopherol 0.01%-1.0%, PEG400/600 0.1%-5.0%, water for injection add to 100%.
Take by weighing TANSHINONES (total tanshinone content 93%) 20mg and be dissolved in an amount of organic solvent, add volatile oil of Lignum Dalbergiae Odoriferae 1g, refined soybean oil or midchain oil 10g, oleic acid 3.5g, high-speed stirred makes mix homogeneously, removes organic solvent in 60 ℃ of distilling under reduced pressure, makes oil phase; Take by weighing salvianolic acid material (total tanshinone content 80%) 30mg, soybean phospholipid 1.5g, solutolHS150.5g, glycerol 4g, tocopherol 60mg, PEG400 0.5g and make abundant dispersion, make water in 60 ℃ of high-speed stirred.The biphase mixing of profit is made primary emulsion in 60 ℃ of high-speed stirred.Get primary emulsion, water for injection adds to recipe quantity, and regulating pH value is 5.0～7.0, is transferred in the high pressure dispersing emulsification machine, emulsifying is to emulsion droplet mean diameter≤0.5 micron repeatedly, and the fill of aseptic filtration inflated with nitrogen, sterilization are both.
Prescription five: tanshinone material 0.001%-1.0%, salvianolic acid material 0.001%-1.0%, volatile oil of Lignum Dalbergiae Odoriferae 0.5%-5.0%, phosphatidase 10 .5%-4.0%, solutolHS15 0.1%-3.0%, glycerol 1.0%-6.0%, triglyceride 5%-20%, oleic acid 1.0%-6.0%, tocopherol 0.01%-1.0%, PEG400/600 0.1%-5.0%, water for injection add to 100%.
Take by weighing TANSHINONES (total tanshinone content 93%) 20mg and be dissolved in an amount of organic solvent, add volatile oil of Lignum Dalbergiae Odoriferae 1g, refined soybean oil or midchain oil 10g, oleic acid 3.6g, high-speed stirred makes mix homogeneously, removes organic solvent in 60 ℃ of distilling under reduced pressure, makes oil phase; Take by weighing salvianolic acid material (total tanshinone content 80%) 30mg, soybean phospholipid 1.5g, solutolHS15 0.5g, glycerol 4g, tocopherol 50mg, PEG400/600 0.5g and make abundant dispersion, make water in 60 ℃ of high-speed stirred.The biphase mixing of profit is made primary emulsion in 60 ℃ of high-speed stirred.Get primary emulsion, water for injection adds to recipe quantity, and regulating pH value is 5.0～7.0, is transferred in the high pressure dispersing emulsification machine, emulsifying is to emulsion droplet mean diameter≤0.5 micron repeatedly, and the fill of aseptic filtration inflated with nitrogen, sterilization are both.
Prescription six: tanshinone material 0.001%-1.0%, salvianolic acid material 0.001%-1.0%, volatile oil of Lignum Dalbergiae Odoriferae 0.5%-5.0%, phosphatidase 10 .5%-4.0%, glycerol 1.0%-6.0%, ethyl oleate 5%-20%, oleic acid 1.0%-6.0%, tocopherol 0.01%-1.0%, water for injection add to 100%.
Take by weighing TANSHINONES (total tanshinone content 93%) 15mg and be dissolved in an amount of organic solvent, add volatile oil of Lignum Dalbergiae Odoriferae 1g, ethyl oleate 10g, oleic acid 3.8g, high-speed stirred makes mix homogeneously, removes organic solvent in 60 ℃ of distilling under reduced pressure, makes oil phase; Take by weighing salvianolic acid material (total tanshinone content 80%) 25mg, soybean phospholipid 2.5g, glycerol 4g, tocopherol 80mg and make abundant dispersion, make water in 60 ℃ of high-speed stirred.The biphase mixing of profit is made primary emulsion in 60 ℃ of high-speed stirred.Get primary emulsion, water for injection adds to recipe quantity, and regulating pH value is 5.0～7.0, is transferred in the high pressure dispersing emulsification machine, emulsifying is to emulsion droplet mean diameter≤0.5 micron repeatedly, and the fill of aseptic filtration inflated with nitrogen, sterilization are both.
Prescription seven: tanshinone material 0.001%-1.0%, salvianolic acid material 0.001%-1.0%, volatile oil of Lignum Dalbergiae Odoriferae 0.5%-5.0%, phosphatidase 10 .5%-4.0%, solutolHS15 0.1%-3.0%, glycerol 1.0%-6.0%, ethyl oleate 5%-20%, oleic acid 1.0%-6.0%, tocopherol 0.01%-1.0%, PEG400/600 0.1%-5.0%, water for injection add to 100%.
Take by weighing TANSHINONES (total tanshinone content 93%) 15mg and be dissolved in an amount of organic solvent, add volatile oil of Lignum Dalbergiae Odoriferae 1g, ethyl oleate 10g, oleic acid 3g, high-speed stirred makes mix homogeneously, removes organic solvent in 60 ℃ of distilling under reduced pressure, makes oil phase; Take by weighing salvianolic acid material (total tanshinone content 80%) 22mg, soybean phospholipid 1.2g, solutolHS15 0.5g, glycerol 4g, tocopherol 50mg, PEG400/600 0.5g and make abundant dispersion, make water in 60 ℃ of high-speed stirred.The biphase mixing of profit is made primary emulsion in 60 ℃ of high-speed stirred.Get primary emulsion, water for injection adds to recipe quantity, and regulating pH value is 5.0～7.0, is transferred in the high pressure dispersing emulsification machine, emulsifying is to emulsion droplet mean diameter≤0.5 micron repeatedly, and the fill of aseptic filtration inflated with nitrogen, sterilization are both.
Embodiment 2 (nanometer microemulsion type)
Prescription one: tanshinone material 0.001%-1.0%, salvianolic acid material 0.001%-1.0%, volatile oil of Lignum Dalbergiae Odoriferae 0.5%-5.0%, solutolHS15 0.1%-5.0%, dehydrated alcohol 0.01%-8%, water for injection add to 100%.
Take by weighing TANSHINONES (total tanshinone content 93%) 15mg, volatile oil of Lignum Dalbergiae Odoriferae 1g and be dissolved in the 1g ethanol, add solutolHS151.0g and suitable quantity of water and make mix homogeneously in 40 ℃ of stirrings; Take by weighing salvianolic acid material (total tanshinone content 80%) 20mg and be dissolved in the suitable quantity of water, both are settled to 100ml at mixing, make microemulsion in 40 ℃ of high-speed stirred.Regulating pH value is 5.0～7.0, the fill of aseptic filtration inflated with nitrogen, and sterilization both got.
Prescription two: tanshinone material 0.001%-1.0%, salvianolic acid material 0.001%-1.0%, volatile oil of Lignum Dalbergiae Odoriferae 0.5%-5.0%, solutolHS15 0.1%-5.0%, dehydrated alcohol 0.01%-8%, ethyl oleate 0.01%-8%, water for injection add to 100%.
Take by weighing TANSHINONES (total tanshinone content 93%) 15mg and be dissolved in the 1g ethanol, add in volatile oil of Lignum Dalbergiae Odoriferae 1g, ethyl oleate 1.0mg, solutolHS15 1.0g and the suitable quantity of water, make mix homogeneously in 40 ℃ of stirrings; Salvianolic acid material (total tanshinone content 80%) 20mg is dissolved in the suitable quantity of water, and both are settled to 100ml at mixing, and regulating pH value is 5.0～7.0, makes microemulsion in 40 ℃ of high-speed stirred.The fill of aseptic filtration inflated with nitrogen, sterilization both got.
Prescription three: tanshinone material 0.001%-1.0%, salvianolic acid material 0.001%-1.0%, volatile oil of Lignum Dalbergiae Odoriferae 0.5%-5.0%, solutolHS15 0.1%-5.0%, medium chain triglyceride 0.01%-5%, dehydrated alcohol 0.01%-8%, PEG400/6000.1%-5.0%, water for injection add to 100%.
Take by weighing TANSHINONES (total tanshinone content 93%) 15mg and be dissolved in the 1g ethanol, add solutolHS15 1.0g, volatile oil of Lignum Dalbergiae Odoriferae 1g, medium chain triglyceride 0.6g and an amount of water for injection, make mix homogeneously in 40 ℃ of stirrings; Salvianolic acid material (total tanshinone content 80%) 20mg, PEG400/600 100mg are dissolved in the suitable quantity of water, and both are settled to 100ml at mixing, and regulating pH value is 5.0～7.0, makes microemulsion in 40 ℃ of high-speed stirred.The fill of aseptic filtration inflated with nitrogen, sterilization both got.
Prescription four: tanshinone material 0.001%-1.0%, salvianolic acid material 0.001%-1.0%, volatile oil of Lignum Dalbergiae Odoriferae 0.5%-5.0% phosphatidase 10 .2%-10.0%, dehydrated alcohol 0.01%-10%, glycerol 0.1%-5.0%, hydroxypropyl 0.1%-5.0%, water for injection add to 100%.
Take by weighing TANSHINONES (total tanshinone content 93%) 15mg, volatile oil of Lignum Dalbergiae Odoriferae 1g and be dissolved in the 1g ethanol, add phosphatidase 11 .2g, glycerol 2g in suitable quantity of water, 40 ℃ of stirrings make mix homogeneously; Salvianolic acid material (total tanshinone content 80%) 20mg, hydroxypropyl 300mg are dissolved in the suitable quantity of water, and both are settled to 100ml at mixing, and regulating pH value is 5.0～7.0, makes microemulsion in 40 ℃ of high-speed stirred.The fill of aseptic filtration inflated with nitrogen, sterilization both got.
Prescription five: tanshinone material 0.001%-1.0%, salvianolic acid material 0.001%-1.0%, volatile oil of Lignum Dalbergiae Odoriferae 0.5%-5.0% polyoxyethylene castor oil 0.1%-5.0%, dehydrated alcohol 0.01%-10%, ethyl oleate 0.01%-10%, water for injection add to 100%.
Take by weighing TANSHINONES (total tanshinone content 93%) 15mg, volatile oil of Lignum Dalbergiae Odoriferae 1g and be dissolved in the 1g ethanol, add in polyoxyethylene castor oil 0.8g, volatile oil of Lignum Dalbergiae Odoriferae 1g, ethyl oleate 1.0g and the suitable quantity of water, make mix homogeneously in 40 ℃ of stirrings; Salvianolic acid material (total tanshinone content 80%) 20mg is dissolved in an amount of water for injection, and both are settled to 100ml at mixing, and regulating pH value is 5.0～7.0, makes microemulsion in 40 ℃ of high-speed stirred.The fill of aseptic filtration inflated with nitrogen, sterilization both got.
Embodiment 3 (pharmacodynamic study data)
Observe the influence of Emulsion of the present invention and commercially available XIANGDAN ZHUSHEYE, the pharmacological action of research Emulsion of the present invention to rats in vitro thrombosis and blood viscosity.The results are shown in following table:
Emulsion of the present invention and commercially available XIANGDAN ZHUSHEYE are to the thrombotic influence of rats in vitro (X ± SD)
| Group | Dosage (/kg) | Number of animals | Thrombosis | ||
| Length (mm) | Weight in wet base (mg) | Dry weight (mg) | |||
| Matched group XIANGDAN ZHUSHEYE group embodiment 1 (prescription one) embodiment 1 (prescription three) embodiment 2 (prescription one) embodiment 2 (prescription three) | ? ?1.5g ?15mg ?15mg ?15mg ?15mg | ????10 ????10 ????10 ????10 ????10 ????10 | ??22.9±1.7 ??20.3±2.2 *??19.2±2.9 ??19.4±2.7 *??19.0±1.6 *??19.7±2.8 ** | ??138.4±14.0 ??117.2±17.5 **??112.6±23.9 ??113.7±26.4 ??113.2±11.7 *??110.0±24.6 ** | 27.2±2.5 21.6±3.2 ***20.4±4.6 *20.7±4.9 20.5±3.0 **20.6±5.0 ** |
Annotate: compare with matched group
*P＜0.05,
*P＜0.01,
* *P＜0.001
By table 1 as seen, compare with matched group, the present invention writes out a prescription, and 15mg/kg reaches and the thrombosis length of XIANGDAN ZHUSHEYE 1.5g/kg dosage group all obviously shortens (P＜0.05～0.01), and wet weight of thrombus and dry weight all obviously alleviate (P＜0.05～0.01); It is little to this shows that Emulsion of the present invention has a consumption, the characteristics that curative effect is high.
Claims (10)
1, a kind of Xiangdan emulsion for injection, it contains Radix Salviae Miltiorrhizae extract, volatile oil of Lignum Dalbergiae Odoriferae, surfactant and water-bearing media, it is characterized in that: this injection is a kind of aqueous dispersion, the mean diameter of decentralized photo≤0.5 micron, the concentration of extract is 0.01%～8.0% in the injection, is called nanometer microemulsion formulation or inferior nano-emulsion preparation on pharmaceutics.
2, according to Xiangdan emulsion for injection in the claim 1:
(1) Radix Salviae Miltiorrhizae extract is characterized in that containing tanshinone material and salvianolic acid material, and wherein the content of tanshinone material in liposoluble extract is 50-99.99%, and salvianolic acid material content in water solubility extract is 50-99.99%.
(2) volatile oil of Lignum Dalbergiae Odoriferae is characterized in that the Lignum Dalbergiae Odoriferae medical material is through vapor distillation or CO
2Supercritical extraction is carried.
(3) surfactant is characterized in that being selected from: one or more in phospholipid (plant phospholipid, animal phospholipid, synthetic phospholipid), propylene glycol, fatty glyceride, solutolHS15, labrosol, Tweens, poloxamer series, polyoxyethylene fatty acid ester, Polyethylene Glycol and derivant series thereof, hydroxypropyl, the hydroxypropyl Υ-cyclodextrin; Can also add triglyceride in the surfactant or as the glycerol of isotonic agent, wherein triglyceride comprises vegetable oil or medium chain triglyceride, can also add fatty acid or aliphatic alcohol or its sodium salt as co-emulsifier, cholic acid or deoxycholic acid and sodium salt thereof, wherein the carbon number that comprises of fatty acid or aliphatic alcohol can be from 6-24, antioxidant such as tocopherol (vitamin E) or L-ascorbyl palmitate can also be added, cosolvent ethanol can also be added.
3, according to Xiangdan emulsion for injection among the claim 1-2, it is characterized in that by weight, contain tanshinone material 0.001%-1.0%, salvianolic acid material 0.001%-1.0%, volatile oil of Lignum Dalbergiae Odoriferae 0.5%-5.0%, surfactant 1.0%-30.0%, water for injection and add to 100%.
4, according to the surfactant in the claim 3, it is characterized in that by weight, contain phospholipid 0.5%-4.0%, glycerol 1.0%-6.0%, triglyceride 5%-20%, oleic acid 1.0%-6.0%; Can also contain tocopherol 0.01%-1.0%.
5, according to the surfactant in the claim 3, it is characterized in that by weight, contain phospholipid 0.5%-4.0%, glycerol 1.0%-6.0%, triglyceride 5%-20%, oleic acid 1.0%-6.0%; Can also contain solutolHS15 0.1%-3.0%, tocopherol 0.01%-1.0%; Can also contain hydroxypropyl 0.5%-5.0% or PEG400/600 0.1%-5.0%.
6, according to the surfactant in the claim 3, it is characterized in that by weight, contain phospholipid 0.5%-4.0%, glycerol 1.0%-6.0%, ethyl oleate 5%-20%, oleic acid 1.0%-6.0%; Can also contain solutolHS15 0.1%-3.0%, tocopherol 0.01%-1.0%; Can also contain PEG400/600 0.1%-5.0%.
7, according to the surfactant in the claim 3, it is characterized in that by weight, contain solutolHS15 0.1%-5.0%, dehydrated alcohol 0.01%-8%, can also contain medium chain triglyceride or ethyl oleate 0.01%-5%, can also contain PEG400/600 0.1%-5.0% or hydroxypropyl 0.1%-5.0%.
8, according to the surfactant in the claim 3, it is characterized in that by weight, contain phospholipid 0.2%-10.0%, dehydrated alcohol 0.01%-10%, can also contain glycerol 0.1%-5.0%, can also contain PEG400/600 0.1%-5.0% or hydroxypropyl 0.1%-5.0%.
9, according to the surfactant in the claim 3, it is characterized in that by weight, contain polyoxyethylene castor oil 0.1%-5.0%, dehydrated alcohol 0.01%-10%, can also contain glycerol or ethyl oleate 0.01%-10.0%.
10, according to Xiangdan emulsion for injection in the claim 1, it is characterized in that according to injection in the claim 1, tanshinone material and volatile oil of Lignum Dalbergiae Odoriferae can be made nano-emulsion preparation or inferior nano-emulsion preparation separately, the salvianolic acid material is made liquid drugs injection, during administration with tanshinone emulsion with danshensu liquid drugs injection dilution posterior vein drop or inject; Also tanshinone material and volatile oil of Lignum Dalbergiae Odoriferae can be made the decentralized photo of Emulsion, during the salvianolic acid material is soluble in the aqueous phase, during administration with an amount of 0.9% sodium chloride solution or 5% glucose dilution posterior vein drop or inject.Its preparation method is as follows:
A) tanshinone material and volatile oil of Lignum Dalbergiae Odoriferae are dissolved in triglyceride or the ethyl oleate, make oil phase in 50-90 ℃ of high-speed stirred, all the other components are dissolved in the suitable quantity of water, make water in 50-90 ℃ of high-speed stirred, the biphase 50-90 of being mixed in of a profit ℃ high-speed stirred is made primary emulsion, and the adjusting pH value is 5.0-7.0.
B) get primary emulsion in above-mentioned (a), water for injection adds to recipe quantity, is transferred in the high pressure dispersing emulsification machine, and emulsifying is to emulsion droplet mean diameter≤0.5 micron repeatedly.
C) after the Emulsion of getting above-mentioned (b) filtered, inflated with nitrogen fill, sterilization were both.
Wherein the nanometer microemulsion formulation only needs high-speed stirred to form, and does not need the emulsifying of high pressure dispersing emulsification machine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510059756 CN1686372A (en) | 2005-03-31 | 2005-03-31 | Xiangdan emulsion for injection and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510059756 CN1686372A (en) | 2005-03-31 | 2005-03-31 | Xiangdan emulsion for injection and its preparation method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1686372A true CN1686372A (en) | 2005-10-26 |
Family
ID=35304414
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200510059756 Pending CN1686372A (en) | 2005-03-31 | 2005-03-31 | Xiangdan emulsion for injection and its preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1686372A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103070898A (en) * | 2013-01-29 | 2013-05-01 | 广东药学院 | Salvia miltiorrhiza and panax notoginseng compound nano suspension |
| CN103919759A (en) * | 2014-04-06 | 2014-07-16 | 吴静 | Pharmaceutical composition comprising salvianic acid a sodium and salvianolic acid F and preparation of pharmaceutical composition |
-
2005
- 2005-03-31 CN CN 200510059756 patent/CN1686372A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103070898A (en) * | 2013-01-29 | 2013-05-01 | 广东药学院 | Salvia miltiorrhiza and panax notoginseng compound nano suspension |
| CN103070898B (en) * | 2013-01-29 | 2014-04-30 | 广东药学院 | Salvia miltiorrhiza and panax notoginseng compound nano suspension |
| CN103919759A (en) * | 2014-04-06 | 2014-07-16 | 吴静 | Pharmaceutical composition comprising salvianic acid a sodium and salvianolic acid F and preparation of pharmaceutical composition |
| CN103919759B (en) * | 2014-04-06 | 2016-03-16 | 吴静 | A kind of containing danshensu sodium, the pharmaceutical composition of salvia miltiorrhiza tanshinoate F and preparation thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1305006B1 (en) | Process for the manufacture of dispersions for formulating slightly or poorly soluble active ingredients | |
| JP2010534555A (en) | Complex emulsifier, emulsion prepared using the same, and preparation method thereof | |
| DE60313299T2 (en) | Self-regulating systems for the delivery of TAXOIDS | |
| EP2079473B1 (en) | Dermatological composition containing avermectin nanocapsules, method for preparing the same and uses thereof | |
| CN101829061A (en) | Taxol nanoparticle composition and preparation method thereof | |
| WO2022160970A1 (en) | Concentrated solution of insoluble drug not containing ethanol, and micellar solution prepared therefrom | |
| EP2637655B1 (en) | Pharmaceutical composition of taxoids | |
| TW201717932A (en) | Diacerein or rhein topical formulations and uses thereof | |
| CN113197852B (en) | Cannabidiol nano micelle preparation and preparation method thereof | |
| KR20140041952A (en) | Submicro emulsion of paclitaxel using steroid complex as intermediate carrier | |
| US20100130619A1 (en) | Pharmaceutical composition for parenteral administration of idebenone | |
| CN101601648B (en) | Sub-microemulsion used for intravenous injection of polyene yew alcohol phospholipid composite and preparation method thereof | |
| US20100056644A1 (en) | Pharmaceutical compositions containing anhydrous calcipotriene | |
| US20070042009A1 (en) | Topical composition for delivery of salicylates | |
| CN101524329A (en) | Bicyclo-ethanol submicron emulsion and preparation method thereof | |
| CN1701808A (en) | Emulsion of red sage root for injection and its preparation process | |
| US20130289102A1 (en) | Amyris alcohol and its ester for treating acne | |
| CN1686372A (en) | Xiangdan emulsion for injection and its preparation method | |
| EP2384188B1 (en) | Pharmaceutical microemulsion for preventing supramolecular aggregation of amphiphilic molecules | |
| CN108014104A (en) | A kind of Synergistic type dihydromyricetin soluble type compound and preparation method thereof | |
| US20130039978A1 (en) | Medicinal compositions and method for treatment of urinary tract infections | |
| CN1810240A (en) | Prepn process and use of total andrographolide emulsion | |
| KR102263606B1 (en) | Nanomicells comprising paclitaxel and alpinumisoflavone, method of production and use thereof | |
| CN1759828A (en) | Fat emulsion of biobalide B and preparation method | |
| CN101073566A (en) | Production and use for tanshinone component injection |
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 |