CN102139092A - Leech freeze-dried powder injection solution for injection and preparation method thereof - Google Patents
Leech freeze-dried powder injection solution for injection and preparation method thereof Download PDFInfo
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- CN102139092A CN102139092A CN2011100679748A CN201110067974A CN102139092A CN 102139092 A CN102139092 A CN 102139092A CN 2011100679748 A CN2011100679748 A CN 2011100679748A CN 201110067974 A CN201110067974 A CN 201110067974A CN 102139092 A CN102139092 A CN 102139092A
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- hirudo
- powder
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- leech
- lyophilized injectable
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Abstract
The invention discloses leech freeze-dried powder injection solution for injection and a preparation method thereof. A leech medicinal material recorded in Chinese pharmacopeia is used as a raw material, and the preparation method comprises the following steps of: crushing the leech medicinal material; performing soaking extraction and seeping extraction by using 0 to 80 percent acetone/acetone aqueous solution or ethanol/ethanol aqueous solution in an amount which is 1 to 100 times the raw materials at the temperature of between 0 and 80 DEG C; concentrating extracting solution under reduced pressure; precipitating with 60 percent ethanol to remove impurities; concentrating mother liquor under reduced pressure; precipitating with 85 percent ethanol; precipitating and performing vacuum drying to obtain leech polypeptide powder; and compounding the leech polypeptide powder, a freeze-dried powder proppant and an osmotic pressure regulator to obtain the powder injection solution by a freezing-drying technology. The preparation is mainly used for preventing and treating cardiovascular and cerebrovascular diseases. Compared with hospital preparations of leech injection solution and market-sold formula solid preparations, the powder injection solution has the advantages of obvious activity, high stability, long validity and the like, and is convenient to store and transport.
Description
Technical field
The present invention relates to a kind of drug for injection Hirudo lyophilized injectable powder, also relate to the preparation method of this injectable powder simultaneously.
Background technology
Cardiovascular and cerebrovascular disease is one of principal disease of harm humans health, accounts for 1/3rd of global dead factor, and the trend of growth is arranged.At present, China just progressively steps into aging society, and the demand of anticoagulant is increasing, but traditional urea kinases and heparin all have hemorrhage drawback after the administration, have limited its clinical practice.
Hirudo, beginning is stated from Shennong's Herbal, 2010 editions one Hirudo medical material that records of the Pharmacopoeia of the People's Republic of China is the dry body of Hirudo Whitmania pigra, blood-eating hirudo Hirudo nipponica and Folium Salicis Babylonicae Hirudo Whitmania acranulatc, its property is put down, distinguishes the flavor of bitter, the effect of have removing blood stasis, removing blood stasis, stimulating the menstrual flow, in China long medicinal history being arranged, is the medicine of the Chinese medicine treating blood disorders of classics.The Hirudo injection is used for many years at a plurality of large hospitals as hospital preparation, but because its active component is the peptide class, lack stabilization time in water, prepares with preceding need temporarily, limited it greatly in clinical use.Therefore, safe, effective, the quality controllable Hirudo lyophilized injectable powder of preparation can be used the Hirudo injection more effectively, easily.Patent 03113566,95117701,1569662A and 041376957 are announced is leech active polypeptide such as extracting hirudin from the live body Hirudo, but in China, tradition medication and commercially available Hirudo are exsiccant Hirudo medical material, therefore, the present invention is a feedstock production Hirudo lyophilized injectable powder with exsiccant Hirudo medical material promptly.
Summary of the invention
The object of the present invention is to provide a kind of activity remarkable, and to stable performances such as light, heat, oxygen, water, pollution-free, be convenient to operation, transportation and storage, be applicable to the Hirudo lyophilized injectable powder of large-scale production.
Another object of the present invention provides the preparation method of this injectable powder.
The object of the present invention is achieved like this:
The present invention forms and comprises leech polypeptide powder, lyophilized powder proppant and osmotic pressure regulator, and parts by weight are:
0.01～1 part in leech polypeptide powder
0～90 part of frozen-dried supporting agent
0～15 part of osmotic pressure regulator
The present invention is a lyophilized injectable powder, and pH value is between 5.5～7.5, and optimum pH is between 6.0～7.0.Its purposes is the control of cardiovascular and cerebrovascular disease.Wherein the lyophilized powder proppant is the water solublity proppant, and is soluble in water, and dissolving rapidly is selected from mannitol, albumin, glucose, dextran, gelatin hydrolysate etc. in clinical use; Osmotic pressure regulator specially refers to sodium chloride.
The preparation method of Hirudo lyophilized injectable powder provided by the invention is:
(1) preparation leech polypeptide powder
Water intaking trematodiasis medical material is pulverized, and is loaded in the container with lid, with 0%～80% acetone or the ethanol/water of 1～100 times of amount, soaks extraction or seepage extraction, merge extractive liquid, for 1～10 time in 0～80 ℃ of branch; Extracting solution low temperature reclaims acetone or alcohol, and being evaporated to relative density in 0～80 ℃ is 1.05～1.10; Adding ethanol to ethanol final concentration in the concentrated solution is 60%, stirs evenly, and 0～40 ℃ of standing over night filters, collect filtrate, being evaporated to relative density in 40 ℃ is 1.05～1.10, adds ethanol once more, and making alcoholic acid final concentration is 85%, stir evenly, 0～40 ℃ of standing over night filters.Collecting precipitation, vacuum drying promptly gets the leech polypeptide powder.
(2) preparation Hirudo freeze-dried powder preparation
The leech polypeptide powder, frozen-dried supporting agent, osmotic pressure regulator of getting recipe quantity mix 3 solution more respectively with the water for injection dissolving, the water for injection standardize solution, under aseptic condition with 0.22 μ m special use membrane filtration; Then according to the amount fill of every 2mL to the cillin bottle of 10mL, the false add plug is placed on and carries out lyophilizing in the freezer dryer.Elder generation's pre-freeze was to-45～-35 ℃ of insulations 1～3 hour, and evacuation in 15～20 hours, rises to temperature-15～-2 ℃, in 2～5 hours, temperature is risen to 30～50 ℃ again, continued to keep vacuum 3～5 hours; Add plug under the vacuum, inflated with nitrogen takes out back jewelling cap seal mouth.
The present invention is with the injectable sterile powder of lyophilization principle preparation compared with prior art, is freeze-dried powder preparation, and pH value is between 6.0～7.0.Have the following advantages: 1. activity is more remarkable; 2. reduced volume and weight, saved the cost of transportation of each process of operation, solved transportation and the storage problem of cold and hot season with the dosage medicine; 3. be convenient to operation, be applicable to large-scale production; 4. the injectable powder water content is lower than 3% (W/W), the phenomenon of having avoided leech polypeptide to degrade easily in aqueous solution.
The specific embodiment
Embodiment 1
A kind of injection Hirudo lyophilized injectable powder, its preparation may further comprise the steps:
(1) preparation leech polypeptide powder:
Get 2.0 kilograms of the dry medical materials of Hirudo, pulverize places container with lid with powder, with 40% acetone of 20 times of volumes, soaks extraction 4 times in 0～4 ℃ of branch, and merge extractive liquid, reclaims acetone, and 40 ℃ are evaporated to relative density is 1.05.Adding ethanol to alcoholic acid final concentration in the concentrated solution is 60%, stirs evenly, and 0～4 ℃ of standing over night filters, abandon precipitation, it is 1.05 that mother solution is evaporated to relative density in 40 ℃, adds ethanol once more, and making alcoholic acid final concentration is 85%, stir evenly, 0～4 ℃ of standing over night filters.Collecting precipitation, vacuum drying to precipitation does not contain the second alcohol and water, promptly gets leech polypeptide powder 100.5 grams.
(2) preparation prescription:
(3) preparation technology:
The leech polypeptide powder, mannitol, sodium chloride of getting recipe quantity mix 3 solution more respectively with the water for injection dissolving, water for injection dilution and standardize solution, under aseptic condition with 0.22 μ m special use membrane filtration; Then according to the amount fill of every 2mL to the cillin bottle of 10mL, the false add plug is placed on and carries out lyophilizing in the freezer dryer.Elder generation's pre-freeze was to-45～-35 ℃ of insulations 1～3 hour, and evacuation in 15～20 hours, rises to temperature-15～-2 ℃, in 2～5 hours, temperature is risen to 30～50 ℃ again, continued to keep vacuum 3～5 hours; Add plug under the vacuum, inflated with nitrogen takes out back jewelling cap seal mouth.
Embodiment 2
A kind of injection Hirudo lyophilized injectable powder, its preparation may further comprise the steps:
(1) preparation leech polypeptide powder:
Get 2.3 kilograms of the dry medical materials of blood-eating hirudo, pulverize places container with lid with powder, with 50% ethanol of 30 times of volumes, soaks extraction 4 times in 20 ℃ of branches, merge extractive liquid,, and 40 ℃ are evaporated to relative density is 1.08.Adding ethanol to alcoholic acid final concentration in the concentrated solution is 60%, stirs evenly, and 20 ℃ of standing over night filter, abandon precipitation, it is 1.08 that mother solution is evaporated to relative density in 40 ℃, adds ethanol once more, and making alcoholic acid final concentration is 85%, stir evenly, 20 ℃ of standing over night filter.Collecting precipitation, vacuum drying to precipitation does not contain the second alcohol and water, promptly gets leech polypeptide powder 108.5 grams.
(2) preparation prescription:
(3) preparation technology:
The leech polypeptide powder, albumin, sodium chloride of getting recipe quantity mix 3 solution more respectively with the water for injection dissolving, water for injection dilution and standardize solution, under aseptic condition with 0.22 μ m special use membrane filtration; Then according to the amount fill of every 2mL to the cillin bottle of 10mL, the false add plug is placed on and carries out lyophilizing in the freezer dryer.Elder generation's pre-freeze was to-45～-35 ℃ of insulations 1～3 hour, and evacuation in 15～20 hours, rises to temperature-15～-2 ℃, in 2～5 hours, temperature is risen to 30～50 ℃ again, continued to keep vacuum 3～5 hours; Add plug under the vacuum, inflated with nitrogen takes out back jewelling cap seal mouth.
Embodiment 3
A kind of injection Hirudo lyophilized injectable powder, its preparation may further comprise the steps:
(1) preparation leech polypeptide powder:
Get 2.2 kilograms of the dry medical materials of Folium Salicis Babylonicae Hirudo, pulverize places container with lid with powder, with 30% acetone of 40 times of volumes, extract merge extractive liquid, in 20 ℃ of seepages, 40 ℃ are evaporated to relative density is 1.10, and adding ethanol to alcoholic acid final concentration is 60%, stirs evenly, 20 ℃ of standing over night filter, and abandon precipitation, it is 1.10 that mother solution is evaporated to relative density in 40 ℃, adds ethanol once more, and making alcoholic acid final concentration is 85%, stir evenly, 20 ℃ of standing over night filter.Collecting precipitation, vacuum drying to precipitation does not contain the second alcohol and water, promptly gets leech polypeptide powder 105.5 grams.
(2) preparation prescription:
(3) preparation technology:
The leech polypeptide powder, glucose, sodium chloride of getting recipe quantity mix 3 solution more respectively with the water for injection dissolving, water for injection dilution and standardize solution, under aseptic condition with 0.22 μ m special use membrane filtration; Then according to the amount fill of every 2mL to the cillin bottle of 10mL, the false add plug is placed on and carries out lyophilizing in the freezer dryer.Elder generation's pre-freeze was to-45～-35 ℃ of insulations 1～3 hour, and evacuation in 15～20 hours, rises to temperature-15～-2 ℃, in 2～5 hours, temperature is risen to 30～50 ℃ again, continued to keep vacuum 3～5 hours; Add plug under the vacuum, inflated with nitrogen takes out back jewelling cap seal mouth.
Test example 1 Hirudo lyophilized injectable powder is to the dissolution of external thrombus
1. trial drug
Normal saline (blank group): will eagle chemical reagent factory provides by Shenyang; Urea kinases (positive controls): provide by pharmaceutical factory of Nanjing University; Hirudo lyophilized injectable powder of the present invention: provide by pharmaceutical college of Zhongshan University.
2. experimental animal
White Rabbit, body weight 1.9～3.1kg, male and female dual-purpose are planted by New Zealand.
3. test method
The rabbit ear edge vein exploitating blood, 3.8% liquor sodii citratis adds in 1: 9 ratio, adds Fibrinogen, CaCl then successively
2(55.5gL
-1) and thrombin (1 * 10
5UL
-1), addition is to add 20 μ L Fibrinogens, 10 μ L CaCl in the 1mL blood
2With 20 μ L thrombins.With plastic injector for temporary use blood is injected the polyethylene tube that internal diameter is 3mm fast behind the mixing fast, behind 37 ℃ of water-bath 20min, thrombosis is taken out, be cut into the 1.5cm segment, after dividing its quality of another name, put into and contain Hirudo lyophilized injectable powder high dose (1.0kgL respectively
-1), middle dosage (0.5kgL
-1), low dosage (0.25kgL
-1), urokinase (6 * 10
5UL
-1) and the test tube of each 2mL of normal saline in, will remain the thrombosis section behind 37 ℃ of water-bath 4h and take out and divide another name its quality, calculate the thrombolytic percentage rate.Each mass concentration medicine all repeats 10 times.Thrombolytic percentage rate=[(thrombosis quality behind thrombosis initial mass-drug effect 4h)]/thrombosis initial mass * 100%.
4. result of the test
Result of the test sees Table 1.
Table 1 Hirudo lyophilized injectable powder is to the effect of external thrombus
N=10
* compare P＜0.001 with the normal saline group
Pharmacological tests shows that Hirudo lyophilized injectable powder of the present invention has tangible dissolution to external thrombus, and obvious dose-effect relationship is arranged.
Test example 2 Hirudo freeze-dried powder preparations are to the dissolution of fibrin plate
1. test drug
With test example 1.
2. test method
In plate, add the fibrinogen solution of 9mL 0.5%, add 2 * 10 again
3UL
-1Thrombin solution 1mL, the about 10s of mixing that turns round and round immediately promptly forms the thick fibrin clot of 1mm, adds filter paper at the plate loam cake, promptly forms fibrin plate after 30min is placed at the level place.Get ready-made fibrin plate, place baking 30min in 85 ℃ of baking ovens, be the heating fibrin plate after the cooling.With Hirudo lyophilized injectable powder high dose (1.0kgL
-1), middle dosage (0.5kgL
-1), low dosage (0.25kgL
-1), urokinase (6 * 105uL
-1) and each 20 μ L of normal saline drip to respectively on the fibrin plate, each dot spacing is greater than 1.5cm.Put fibrin plate in the box that wets, put into 37 ℃ of baking ovens, observe behind the 4h to have or not and dissolve circle, and with the diameter that the kind of calliper dissolving is enclosed, calculate and dissolve the circle area, with the size that area size measurement fibrinolytic is enclosed in dissolving, each concentration medicine all repeats 10 times.Dissolving circle area (mm
2)=[(major diameter+minor axis)/4]
2* π.
3. result of the test
Result of the test sees Table 2.
Table 2 Hirudo lyophilized injectable powder is to heating and the dissolution that does not heat fibrin plate
N=10
* compare P＜0.001 with the normal saline group
Pharmacological evaluation shows that Hirudo lyophilized injectable powder of the present invention does not all have obvious dissolution to adding the thermal fiber flat board and adding the thermal fiber flat board, and the effect of comparing with the urokinase group obviously strengthens, and dose-effect relationship is obvious.
Test example 3 Hirudo freeze-dried powder preparations are to the influence of blood plasma recalcification time (PRT)
1. test drug
With test example 1.
2. test method and result
5 of rabbit, every vein is got blood 4.5mL, add in the centrifuge tube be placed with 3.8% sodium citrate 0.5mL, behind the mixing with 1000rmin
-1Centrifugal 10min gets upper plasma.Get one of 96 orifice plate, every hole adds pooled plasma and each 0.1mL of NS, puts into 37 ℃ of water-bath temperature immediately and bathes 1min, adds 2.775gL
-1CaCl
2Solution 0.1mL, mixing is still put into 37 ℃ of water-baths, begins to use manual time-keeping simultaneously, stops timing when detecting fiber protein yarn with bamboo let.Repeat 10 times, calculate 10 times meansigma methods, be matched group blood plasma recalcification time.Change NS into solution to be measured, obtain to be measured group of blood plasma recalcification time by same procedure.The results are shown in Table 3.
Test example 4 Hirudo freeze-dried powder preparations are to the influence of plasma in rabbit thrombin time (TT)
1. test drug
With test example 1.
2. test method and result
Method by test example 3 prepares pooled plasma.Add pooled plasma and each 0.1mL of NS in 96 orifice plates, incubation 3min in 37 ℃ of water-baths add warm in advance 1 * 10 again
4UL
-1Thrombin 0.1mL, mixing, record clotting of plasma required time.Every group is repeated 10 times, averages.Change NS into solution to be measured, obtain to be measured group of thrombin time of blood plasma by same procedure.The Hirudo lyophilized injectable powder that the results are shown in Table 3,3 dosage groups all can make the thrombin time significant prolongation, and dose-effect relationship is obvious.
Test example 5 Hirudo freeze-dried powder preparations are to the influence of plasma in rabbit prothrombin time (PT)
1. test drug
With test example 1.
2. test method and result
Get 5 in test tube, add thromboplastin and 2.775gL
-1CaCl
2Each 0.1mL of solution adds above-mentioned medicinal liquid 0.1mL respectively, adds plasma in rabbit 0.1mL again.Put into 37 ℃ of water-baths behind the mixing, begin to clock.Slow inclination test tube was 1 time every 2～3 seconds.The record fibrin solidifies the motionless required time of liquid level.Every group is repeated 10 times, averages.The Hirudo lyophilized injectable powder that the results are shown in Table 3,3 dosage groups all can make the prothrombin time significant prolongation.
Table 3 Hirudo lyophilized injectable powder is to the influence of blood plasma recalcification time (PRT), thrombin time (TT) and thrombin (PT)
N=10
* compare P＜0.001 with the normal saline group.
Claims (8)
1. injection Hirudo lyophilized injectable powder, it is characterized in that: its composition comprises leech polypeptide powder, lyophilized powder proppant and osmotic pressure regulator, parts by weight are:
0.01～1 part in leech polypeptide powder
0～90 part of frozen-dried supporting agent
0～15 part of osmotic pressure regulator.
2. Hirudo lyophilized injectable powder according to claim 1 is characterized in that: this injection is a lyophilized injectable powder.
3. Hirudo lyophilized injectable powder according to claim 1 is characterized in that: this injection is used for the control of cardiovascular and cerebrovascular disease.
4. the preparation method of Hirudo lyophilized injectable powder according to claim 2, its feature may further comprise the steps:
(1) preparation leech polypeptide powder
Water intaking trematodiasis medical material is pulverized, and is loaded in the container with lid, with 0%～80% acetone or the ethanol/water of 1～100 times of amount, soaks extraction or seepage extraction for 1～10 time in 0～80 ℃ of branch; Merge extractive liquid,, low temperature reclaims acetone or alcohol, and 0～80 ℃ is evaporated to relative density is 1.05～1.10; Adding ethanol to ethanol final concentration in the concentrated solution is 60%, stirs evenly, and 0～40 ℃ of standing over night filters, and collects filtrate; It is 1.05～1.10 that filtrate is evaporated to relative density in 40 ℃, adds ethanol once more, and making alcoholic acid final concentration is 85%, stirs evenly, and 0～40 ℃ of standing over night filters, collecting precipitation, and the precipitate vacuum drying promptly gets the leech polypeptide powder;
(2) preparation Hirudo lyophilized injectable powder
Get prescription leech polypeptide powder, frozen-dried supporting agent and osmotic pressure regulator,, be divided in the 10mL cillin bottle according to the amount of every 2mL with water for injection dissolving and standardize solution, aseptic filtration; Pre-freeze is incubated 1～3 hour to-45～-35 ℃ then, and evacuation in 15～20 hours, rises to temperature-15～-2 ℃, in 2～5 hours, temperature is risen to 30～50 ℃ again, continues to keep vacuum 3～5 hours; Add plug under the vacuum, inflated with nitrogen takes out back jewelling cap seal mouth.
5. according to claim 1 or 4 described Hirudo lyophilized injectable powder and preparation methoies, it is characterized in that: wherein Hirudo is any among Hirudo Whitmania pigra, blood-eating hirudo Hirudo nipponica and the Folium Salicis Babylonicae Hirudo Whitmania acranulatc.
6. according to claim 1 or 4 described Hirudo lyophilized injectable powder and preparation methoies, it is characterized in that: pH value is between 5.5～7.5.
7. according to claim 1 or 4 described Hirudo lyophilized injectable powder and preparation methoies, it is characterized in that: described lyophilized powder proppant is the water solublity proppant, is selected from mannitol, albumin, glucose, dextran, water gelatin etc.
8. according to claim 1 or 4 described Hirudo lyophilized injectable powder and preparation methoies, it is characterized in that: osmotic pressure regulator specially refers to sodium chloride.
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|---|---|---|---|
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|---|---|---|---|
| CN2011100679748A CN102139092A (en) | 2011-03-21 | 2011-03-21 | Leech freeze-dried powder injection solution for injection and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107510705A (en) * | 2017-09-01 | 2017-12-26 | 荆州市民康生物科技有限公司 | A kind of freeze drying protectant of leech crude extract and lyophilized preservation technique |
| CN112641807A (en) * | 2020-12-30 | 2021-04-13 | 重庆多普泰制药股份有限公司 | Preparation method of leech extract |
| CN113073093A (en) * | 2021-04-25 | 2021-07-06 | 山东中医药大学 | Leech fibrinolytic active protein and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1569226A (en) * | 2004-04-29 | 2005-01-26 | 北京乾露春科技有限公司 | Freeze dried powder injection of hirudin and its preparation method |
| CN1651079A (en) * | 2004-12-23 | 2005-08-10 | 吴梅春 | Shu xue tong (blood coursing free flowing) freeze dried powder snjection agent and its preparation method |
-
2011
- 2011-03-21 CN CN2011100679748A patent/CN102139092A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1569226A (en) * | 2004-04-29 | 2005-01-26 | 北京乾露春科技有限公司 | Freeze dried powder injection of hirudin and its preparation method |
| CN1651079A (en) * | 2004-12-23 | 2005-08-10 | 吴梅春 | Shu xue tong (blood coursing free flowing) freeze dried powder snjection agent and its preparation method |
Non-Patent Citations (2)
| Title |
|---|
| 《时珍国医国药》 20091130 钟山 "蚂蟥冻干粉针的制备及质量研究" 第2.1、2.2节 1-6 第20卷, 第11期 * |
| 钟山: ""蚂蟥冻干粉针的制备及质量研究"", 《时珍国医国药》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107510705A (en) * | 2017-09-01 | 2017-12-26 | 荆州市民康生物科技有限公司 | A kind of freeze drying protectant of leech crude extract and lyophilized preservation technique |
| CN112641807A (en) * | 2020-12-30 | 2021-04-13 | 重庆多普泰制药股份有限公司 | Preparation method of leech extract |
| CN113073093A (en) * | 2021-04-25 | 2021-07-06 | 山东中医药大学 | Leech fibrinolytic active protein and preparation method thereof |
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Application publication date: 20110803 |