CN1907292A - Emulsion of baicalin for injection and its preparation process - Google Patents
Emulsion of baicalin for injection and its preparation process Download PDFInfo
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- CN1907292A CN1907292A CNA200610048137XA CN200610048137A CN1907292A CN 1907292 A CN1907292 A CN 1907292A CN A200610048137X A CNA200610048137X A CN A200610048137XA CN 200610048137 A CN200610048137 A CN 200610048137A CN 1907292 A CN1907292 A CN 1907292A
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Abstract
The invention relates to an emulsion for injection and preparing process, wherein each 1000ml of the injection comprises the following constituents (by weight parts): baikal skullcap root glycosides 1.0-200.0g, vegetable oil for injection 50-300g, emulsifying agent 5-20g, isotonic conditioning agent 20-60g, and balancing water.
Description
Technical field
The present invention relates to Emulsion of a kind of injection and preparation method thereof, especially relate to a kind of emulsion of baicalin for injection that is used for antibiotic, antiviral and various inflammation etc. and preparation method thereof.
Background technology
Baicalin, it is a kind of flavone compound that extracts in the dry root of labiate Radix Scutellariae, it is one of main effective ingredient of Radix Scutellariae, it also is the major quality controlling index components of Radix Scutellariae and preparation thereof, according to the pharmaceutical research report, baicalin has antimicrobial, antiallergic action, blood pressure lowering and effects such as calmness, hepatic cholagogic.The baicalin preparation is used as diseases such as heat-clearing and toxic substances removing, anti-inflammation more clinically.Baicalin is mainly oral formulations at present.
The aqueous solution of baicalin and stability are bad, are insoluble in water and dilute acid soln, are soluble in dilute alkaline soln, but the solution pH value is higher, and baicalin is the more destroyed.So it is bigger to make the injection difficulty, do not see the report of listing so far.
The oral formulations of baicalin is mainly tablet, but slow through gastrointestinal absorption during the baicalin oral administration, and administration just detected in blood about 1 hour, and had tangible first pass effect.So oral administration is not very desirable, bioavailability is low and curative effect is unstable, makes its drug effect be difficult to performance.
The preparation of baicalin has the patent of freeze-dried powder (as number of patent application: 200410067338.5), do not propose how to solve its water solublity problem, while is according to [Colleges Of Traditional Chinese Medicine Of Guangxi's journals such as the Qin of pharmacological room three seas of Guangxi Medical University, 2003,4 (6): 72～74] report, this common freeze-dried powder intravenously administrable metabolism is eliminated very fast, and elimination rate constant β is generally 0.3h
-1About, the time of keeping effective blood drug concentration is also shorter, t
1/2For about 0.16h.This is extremely inconvenient on clinical administration, and drug effect instability and dosage are wayward, and significant limitation is arranged.
The difficult point of the injection research of baicalin also has baicalin to have the effect of chelated metal ions, after entering human body, metal ion in the direct chelating blood of meeting, thereby influence the activity of some enzymes, this is common injection and the unavoidable toxic and side effects of lyophilizing, so far do not solve report so injection does not go on the market.
How effectively to utilize baicalin, allow it bring into play maximum clinical effect, the treatment disease is the problem of formulation specialist research always, and its research was never stopped.Xu Wenying etc. have carried out studying [medical Leader to its liposome, 2005,7 (24): 624～626], but it is in the experimental stage, but will use a large amount of organic molten coals in this technology, as methanol or chloroform, dichloromethane, this organic molten coal is bigger to human toxicity, can not bring end product into, how eliminate with how suitability for industrialized production is a scabrous problem.Liposome has brought difficulty for big production, brings hidden danger also for the safety of medication and production.Be difficult to produce listing and serve the patient.
Summary of the invention
The present invention is intended to overcome unstability, the slightly solubility of above-mentioned dosage form principal agent and avoids first pass effect, bioavailability is low, drug effect can not reach the big problem of production difficulty lastingly, provide a kind of toxic reaction and zest little, effective drug duration is long, and has the emulsion of baicalin for injection and preparation method thereof of the low dosage of persistence and targeting.
The present invention adopts following technical scheme:
The present invention contains following composition by weight in 1000 milliliters of injection:
Baicalin 1.0～200.0g
Injection vegetable oil 50～300g
Emulsifying agent 5～20g
Isoosmotic adjusting agent 20～60g
Surplus is a water.
The present invention contains following composition by weight in 1000 milliliters of injection:
Baicalin 5.0～100.0g
Injection vegetable oil 100～200g
Emulsifying agent 10～15g
Isoosmotic adjusting agent 22.5～55g
Surplus is a water.
Injection vegetable oil of the present invention is selected from any in soybean oil, safflower oil, Semen Maydis oil, olive oil or the Oleum sesami vegetative grease.
Emulsifying agent of the present invention is selected one or more in soybean lecithin, Ovum Gallus domesticus Flavus lecithin, cholesterol, the poloxamer (Poloxamer) for use.
Isoosmotic adjusting agent of the present invention is selected any in glycerol, xylitol, glucose, sorbitol or the fructose for use.
Preparation method of the present invention is dissolved in isoosmotic adjusting agent in the water for injection, emulsifying agent and baicalin are dissolved in the injection vegetable oil, be heated to 55 ℃～85 ℃ respectively, mixing, elder generation's dispersion and emulsion in tissue mashing machine, again through the emulsifying of high speed dispersing emulsification machine to meeting the preparation particle diameter, add the injection water to 1000, fill promptly gets emulsion of baicalin for injection.
Preparation method of the present invention is with baicalin, emulsifying agent is dissolved in the injection vegetable oil, isoosmotic adjusting agent is dissolved in the water for injection, be heated to 55 ℃～85 ℃ respectively, mixing, first dispersion and emulsion in tissue mashing machine, again through the emulsifying of high speed dispersing emulsification machine to meeting the preparation particle diameter, add the cooling of injection water to 1000, fill promptly gets emulsion of baicalin for injection.
Preparation method of the present invention is dissolved in emulsifying agent in the isoosmotic adjusting agent, be heated to 55 ℃～85 ℃, earlier with tissue mashing machine after 8000～12000 rev/mins of stirrings disperse for three times, oil solution with baicalin and injection vegetable oil adds again, under same speed conditions, stir and carry out emulsifying for three times and disperse, again through the emulsifying of high speed dispersing emulsification machine to meeting the preparation particle diameter, add injection water to 1000, cooling, fill promptly gets emulsion of baicalin for injection.
Preparation method of the present invention described in tissue mashing machine dispersion and emulsion, be meant that stirring three times with tissue mashing machine in 8000～12000 rev/mins disperses.
Also can add membrane stabilizer in the described injectable emulsion, as oleic acid or enuatrol.
Also can add antioxidant vitamin E etc. in the described injectable emulsion.
Route of administration of the present invention mainly adopts the vein mode.
The invention has the advantages that:
1, injectable emulsion of the present invention be with lipomul as carrier, and as soybean lecithin, Ovum Gallus domesticus Flavus lecithin, cholesterol etc. as emulsifying agent.
2, because as soybean oil, the Flos Carthami wet goods composition of oil phase, and all nontoxic to human body as the compositions such as phospholipid of emulsifying agent, its clinical application is for many years, and is safe and reliable, and can be the metabolism of human body institute, therefore can be satisfactorily as the carrier of baicalin.
3, after baicalin is made into Emulsion, solved the stable of blood drug level after its dissolubility, stability and the administration well, avoided directly contacting with blood, exempted the metal ion in its chelating blood, keep the activity of enzyme, and prolonged action time in vivo, thereby improved curative effect, reduce dosage, alleviated toxic and side effects.So said preparation has novelty, practicality and novelty, has solved an indeterminable in the past difficult problem.
4, owing to compositions such as injection soybean oil and/or soybean lecithin have used as fat milk transfusion, therefore injectable emulsion of the present invention is being given the radiocurable while, can also play the dual function of supplying with patient's energy, positive role has been played in the raising of medical effect and medical level.
6, treatment such as the present invention's, antiviral antibiotic to being used for and various inflammation has positive effect.
Stability test
With the Emulsion that makes (lot number: 20060101) and baicalin for injection liquid, lot number: 20060102) carried out comparative study, investigated and the results are shown in following table.
(40 ℃) 6 months stability tests
| Lot number | Time (moon) | Outward appearance | Lactone B labelled amount (%) |
| 20060101 | 0 | Yellow fraction white | 100.0 |
| 1 | Yellow fraction white | 99.1 | |
| 2 | Yellow fraction white | 98.3 | |
| 3 | Yellow fraction white | 97.6 | |
| 6 | Yellow fraction white | 96.8 | |
| 20060102 | 0 | Weak yellow liquid | 100.0 |
| 1 | Weak yellow liquid | 69.9 | |
| 2 | Weak yellow liquid | 49.2 | |
| 3 | Weak yellow liquid | 40.7 | |
| 6 | Yellow liquid | 38.6 |
Illustrate: above test is the data based on labelled amount of the present invention 0 month;
Studies show that by last table:
The Emulsion that the present invention makes makes all complete reservation of the composition of baicalin, stable content.From the gained data analysis, can satisfy the relevant medicine requirement of country through accelerated test measured result of the present invention, and the injection content of contrast is very low, the accelerated test tamper indicating is serious.
Pharmacological testing
Pharmacological room's [Colleges Of Traditional Chinese Medicine Of Guangxi's journal according to Guangxi Medical University, 2003,4 (6): 72～74] reported method utilizes the Emulsion (self-control lot number 20060101) and the freeze-dried powder (self-control lot number 20060103) that make to carry out preliminary intravenously administrable research, and result of the test is as follows:
| Lot number | Elimination rate constant β | t 1/2 |
| 20060101 | 0.82h -1 | 1.23h |
| 20060103 | 0.26h -1 | 0.11h |
The result shows; Result of study basically identicals such as common freeze-dried powder experimental result and Qin Sanhai, and the elimination rate constant β of Emulsion and half-life t
1/2Obviously prolong, thereby reach the raising curative effect, reduce dosage, alleviate the purpose of toxic and side effects.
Safety testing
Example is carried out anaphylaxis, hemolytic and irritation test, draw 10.0% emulsion of baicalin for injection and dilute in right amount in the back adding 2% rabbit erythrocyte normal saline, 37 ℃ of temperature were incubated 4 hours, and not seeing has haemolysis and red cell agglutination.Cavia porcellus anaphylaxis test shows behind the sensitizing injection 14 days and 21 days, and in 15 minutes, 2% emulsion of baicalin for injection anaphylaxis belongs to negative reaction after the booster injection.In order to avoid ear auricular vein injection 5/kg2.0% emulsion of baicalin for injection, after suitably handling, once a day, continuous three days, the injection site is the swollen and erythema of water breakthrough not, and did not also find blood vessel irritation damage phenomenon through histopathologic examination.Injectable emulsion of the present invention does not have anaphylaxis, hemolytic, and also nonirritant reaction is safe.
The specific embodiment
Embodiment 1
Glycerol 22.5g, refining Semen sojae atricolor fourth of the twelve Earthly Branches phosphatidase 11 2.0g are dissolved in the water for injection, baicalin 15.0g is dissolved in the refined soybean oil, be heated to about 55 ℃ respectively, mixing, elder generation's dispersion and emulsion in tissue mashing machine, promptly stir in 8000～12000 rev/mins and disperse for three times with tissue mashing machine, again through the emulsifying of high speed dispersing emulsification machine to meeting the preparation particle diameter, be that the vein emulsion particle diameter must not be lower than 80% less than 1 μ m, and must not detect particle diameter greater than 5 μ m, and add injection water to 1000, be cooled to room temperature, fill, sterilization promptly gets emulsion of baicalin for injection.This technology is 1000 prescription, and production can enlarge, and needs nitrogen protection in the production process.
Embodiment 2
Sorbitol 25.0g is dissolved in the water for injection, and refined lecithin 10g, baicalin 20.0g are dissolved in the refined maize oil, are heated to 70 ℃ respectively, mixing, first dispersion and emulsion in tissue mashing machine, again through the emulsifying of high speed dispersing emulsification machine to meeting the preparation particle diameter.Add injection water to 1000, be cooled to room temperature, fill promptly gets emulsion of baicalin for injection.
Embodiment 3
Xylitol 55.5g is dissolved in the water for injection, refined lecithin 15.0g is molten, baicalin 50.0g in refining Oleum sesami, be heated to 80 ℃ respectively, mixing, dispersion and emulsion in tissue mashing machine earlier, again through the emulsifying of high speed dispersing emulsification machine to meeting the preparation particle diameter.Add injection water to 1000, cooling, fill promptly gets emulsion of baicalin for injection.
Embodiment 4
Baicalin 100.0g, refine yolk lecithin 10.0g are dissolved in the refining safflower oil of 100g, and fructose 20.0g is dissolved in the water for injection, is heated to 60 ℃ respectively, mixing, dispersion and emulsion in tissue mashing machine earlier, again through the emulsifying of high speed dispersing emulsification machine to meeting the preparation particle diameter.Add the cooling of injection water to 1000, fill promptly gets emulsion of baicalin for injection.
Embodiment 5
Baicalin 200.0g, refining soybean lecithin 15.0g are dissolved in the 100.0g refined soybean oil, glucose 50.0g is dissolved in the water for injection, is heated to 55 ℃ respectively, mixing, first dispersion and emulsion in tissue mashing machine, again through the emulsifying of high speed dispersing emulsification machine to meeting the preparation particle diameter.Add the cooling of injection water to 1000, fill promptly gets emulsion of baicalin for injection.
Embodiment 6
With Ovum Gallus domesticus Flavus lecithin 20.0g, be dissolved in the solution that contains xylitol 50.0g, be heated to 75 ℃, earlier with tissue mashing machine after 8000～12000 rev/mins of stirrings disperse for three times, oil solution with baicalin and refined soybean oil 100.0g adds again, under same speed conditions, stir and carry out emulsifying for three times and disperse, again through the emulsifying of high speed dispersing emulsification machine to meeting the preparation particle diameter.Add injection water to 1000, cooling, fill promptly gets emulsion of baicalin for injection.
Embodiment 7
With Semen sojae atricolor fourth of the twelve Earthly Branches phosphatidase 11 5.0g, be dissolved in the solution that contains glycerol 22.5g, be heated to 85 ℃, earlier with tissue mashing machine after 8000～12000 rev/mins of stirrings disperse for three times, oil solution with baicalin and refining olive oil 100.0g adds again, under same speed conditions, stir and carry out emulsifying for three times and disperse, again through the emulsifying of high speed dispersing emulsification machine to meeting the preparation particle diameter.Add injection water to 1000, cooling, fill, sterilization promptly gets emulsion of baicalin for injection.
Claims (9)
1, a kind of emulsion of baicalin for injection is characterized in that containing following composition by weight in 1000 milliliters of injection:
Baicalin 1.0～200.0g
Injection vegetable oil 50～300g
Emulsifying agent 5～20g
Isoosmotic adjusting agent 20～60g
Surplus is a water.
2, a kind of emulsion of baicalin for injection according to claim 1 is characterized in that containing following composition by weight in 1000 milliliters of injection:
Baicalin 5.0～100.0g
Injection vegetable oil 100～200g
Emulsifying agent 10～15g
Isoosmotic adjusting agent 22.5～55g
Surplus is a water.
3, a kind of emulsion of baicalin for injection according to claim 1 and 2 is characterized in that described injection vegetable oil is selected from any in soybean oil, safflower oil, Semen Maydis oil, olive oil or the Oleum sesami vegetative grease.
4, a kind of emulsion of baicalin for injection according to claim 1 and 2 is characterized in that described emulsifying agent selects one or more in soybean lecithin, Ovum Gallus domesticus Flavus lecithin, cholesterol, the poloxamer for use.
5, a kind of emulsion of baicalin for injection according to claim 1 and 2 is characterized in that described isoosmotic adjusting agent selects any in glycerol, xylitol, glucose, sorbitol or the fructose for use.
6, a kind of preparation method of emulsion of baicalin for injection according to claim 1, it is characterized in that isoosmotic adjusting agent is dissolved in the water for injection, emulsifying agent and baicalin are dissolved in the injection vegetable oil, heat 55 ℃-85 ℃ respectively, mixing, first dispersion and emulsion in tissue mashing machine, again through the emulsifying of high speed dispersing emulsification machine to meeting the preparation particle diameter, add injection water to 1000, fill promptly gets emulsion of baicalin for injection.
7, a kind of preparation method of emulsion of baicalin for injection according to claim 1, it is characterized in that baicalin, emulsifying agent is dissolved in the injection vegetable oil, isoosmotic adjusting agent is dissolved in the water for injection, is heated to 55 ℃-85 ℃ respectively, mixing, elder generation's dispersion and emulsion in tissue mashing machine, again through the emulsifying of high speed dispersing emulsification machine to meeting the preparation particle diameter, add injection water to 1000 cooling, fill promptly gets emulsion of baicalin for injection.
8, a kind of preparation method of emulsion of baicalin for injection according to claim 1, it is characterized in that emulsifying agent is dissolved in the isoosmotic adjusting agent, be heated to 55 ℃-85 ℃, earlier with tissue mashing machine after 8000～12000 rev/mins of stirrings disperse for three times, oil solution with baicalin and injection vegetable oil adds again, under same speed conditions, stir and carry out the emulsifying dispersion for three times, again through the emulsifying of high speed dispersing emulsification machine to meeting the preparation particle diameter, add injection water to 1000, cooling, fill promptly gets emulsion of baicalin for injection.
9, according to the preparation method of claim 6 or 7 described a kind of emulsion of baicalin for injection, it is characterized in that described in tissue mashing machine dispersion and emulsion, be meant that stirring three times with tissue mashing machine in 8000～12000 rev/mins disperses.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA200610048137XA CN1907292A (en) | 2006-08-14 | 2006-08-14 | Emulsion of baicalin for injection and its preparation process |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA200610048137XA CN1907292A (en) | 2006-08-14 | 2006-08-14 | Emulsion of baicalin for injection and its preparation process |
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| CN1907292A true CN1907292A (en) | 2007-02-07 |
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| CNA200610048137XA Pending CN1907292A (en) | 2006-08-14 | 2006-08-14 | Emulsion of baicalin for injection and its preparation process |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102335187A (en) * | 2010-07-28 | 2012-02-01 | 复旦大学附属华山医院 | Application of baicalin in preparing medicament for preventing and treating chronic obstructive pulmonary disease |
-
2006
- 2006-08-14 CN CNA200610048137XA patent/CN1907292A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102335187A (en) * | 2010-07-28 | 2012-02-01 | 复旦大学附属华山医院 | Application of baicalin in preparing medicament for preventing and treating chronic obstructive pulmonary disease |
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