CN1843504A - Albumin nanosphere medicine composition and its preparation method and application method - Google Patents
Albumin nanosphere medicine composition and its preparation method and application method Download PDFInfo
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- CN1843504A CN1843504A CNA2006100808432A CN200610080843A CN1843504A CN 1843504 A CN1843504 A CN 1843504A CN A2006100808432 A CNA2006100808432 A CN A2006100808432A CN 200610080843 A CN200610080843 A CN 200610080843A CN 1843504 A CN1843504 A CN 1843504A
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Abstract
The invention relates to an albumin nanosphere composition medicament, method for preparing and use, wherein the composition medicament is prepared from the following raw materials (by weight ratio): albumin 1000-2000, tanshinone IIA salt 20-200, vegetable oil 200000-400000, PEG6000 100-200, N-(2-mercapto propionyl)-glycine 20-100, and lysine hydrochloride 20-30.
Description
Technical field
The present invention relates to a kind of albumin nanosphere medicine composition and preparation thereof and using method.
Background technology
Existing tanshinone class pharmaceutical preparation is conventional injection, the conventional cyclodextrin that adds antioxidant and comprises preparation, conventional freeze dried powder and solid dispersion.The one, do not consider that tanshinone class medicine causes the side effect of pain when injection, make patient be difficult to stand, patient who has even refusal use this medicine.The 2nd, do not notice that the targeting problem of the therapentic part of medicine, sodium tanshinone IIA sulfate and TANSHINONES sodium phosphate are mainly used in treatment cardiovascular and cerebrovascular disease and pulmonary carcinoma, hepatocarcinoma, leukemia, should concentrate to be distributed in blood circulation, pulmonary and liver.In the prior art, though Liposomal formulation also occurred, or even nanoparticle Liposomal formulation, after but these small-particle liposomees enter human body, removed by liver rapidly, in blood circulation, the half-life of this particle only is about 10 minutes, and prior art only considers the antioxidation of external medicine and do not consider intravital oxidation consumption, is difficult to reach by particular target select the requirement that absorbs to the position.Prior art does not consider that medicine enters the problem that how to break through blood-brain barrier in the cerebrovascular, has limited the curative effect performance of this type of medicine.Prior art is not considered the specific targeting of drug distribution to pulmonary, treatment pulmonary carcinoma yet.The tanshinone class drug injection of prior art for preparing adopts activated carbon process, thereby the adsorbed heavy metal ion of the charcoal that exists active carbon to pollute to bring and small carbon granule are to the harm of human body.
Summary of the invention
In order to solve the above-mentioned defective that prior art exists, the invention provides a kind of albumin nanosphere medicine composition, can reach beneficial effects such as the pain that reduces when using, the pollution of no charcoal, long action time and action site be accurate in vivo.
Technical scheme of the present invention is as follows:
The invention provides a kind of albumin nanosphere medicine composition, form by the feedstock production of following parts by weight:
Albumin 1000-2000;
Tanshinone salt 20-200;
Vegetable oil 200000-400000;
PEG6000 100-200；
N-(2-mercapto radical propionyl group)-glycine 20-100;
Lysine hydrochloride 20-30.
Wherein said albumin is meant the combination in any of zein, bovin serum albumin, egg albumen.
Wherein said tanshinone salt is meant the combination in any of sodium tanshinone IIA sulfate, tanshinone sodium phosphate.
Wherein said vegetable oil is meant the combination in any of Semen Maydis oil, Oleum sesami, soybean oil.
The present invention also provides the preparation method of described albumin nanosphere medicine composition, comprises the steps:
1) it is soluble in water to get described amount albumin, make the albumin aqueous solution of 200g-300g/L, add described amount sodium tanshinone IIA sulfate or/and the tanshinone sodium phosphate, dissolving fully, add described amount lysine hydrochloride, PEG600 (Macrogol 600), N-(2-mercapto radical propionyl group)-glycine again, fully dissolving;
2) step 1) gained solution is added in the vegetable oil of described amount, stir 10-20 minute postcooling under the 100-120 ℃ of condition fast to room temperature;
3) the membrane filtration step 2 in usefulness 150nm aperture) gained solution obtains millimicro ball and filtrate, and the average 500nm of millimicro ball sphere diameter cleans lyophilization with cold diethyl ether;
4) with the membrane filtration step 3) gained filtrate in 50nm aperture, obtain the millimicro ball, sphere diameter 50-150nm cleans lyophilization with cold diethyl ether.
A kind of albumin millimicro ball glucose injection that utilizes the preparation of described albumin nanosphere medicine composition is formed by the feedstock production of following parts by weight:
Albumin nanosphere medicine composition 10-100 in tanshinone salt;
Hydroxypropyl methylcellulose 10-20;
Polygeline 1250-2500;
Antioxidant 20-40;
Glucose 12500-25000
Water 250000.
Described antioxidant is meant the combination in any of reduced glutathion, cystine.
The insoluble particle of described hydroxypropyl methylcellulose is better than national regulation.
The preparation method of described albumin millimicro ball glucose injection is as follows:
1) gets the albumin nanosphere medicine composition that contains described amount tanshinone salt;
2) polygeline, antioxidant and the glucose of described amount joined in temperature 50-60 ℃ the water for injection of described amount, dissolving fully, regulating pH value is 5.0, with molecular cut off 10000 daltonian ultrafiltration post ultrafiltration, add described amount hydroxypropyl methylcellulose (before adding, handling 4 hours) in the ultrafiltrate, dissolving fully through 125 ℃;
3) with step 1) gains and step 2) gains mix, and stir, and regulating pH value is 5.0.
A kind of albumin millimicro ball lyophilized injection that utilizes the preparation of described albumin nanosphere medicine composition is formed by the feedstock production of following parts by weight:
Albumin nanosphere medicine composition 10-100 in tanshinone salt;
Hydroxypropyl methylcellulose 10-20;
Polygeline 50-60;
N-(2-mercapto radical propionyl group)-glycine/lysine hydrochloride 60-120;
Water 2000.
The preparation method of described albumin millimicro ball lyophilized injection is as follows:
1) gets the albumin nanosphere medicine composition that contains described amount tanshinone salt;
2) in the water for injection with the polygeline of described amount, described amount that N-(2-mercapto radical propionyl group)-glycine/lysine hydrochloride joins temperature 50-60 ℃, dissolving fully, regulating pH value is 5.0, with molecular cut off 10000 daltonian ultrafiltration post ultrafiltration, add described amount hydroxypropyl methylcellulose (before adding, handling 4 hours) in the ultrafiltrate, dissolving fully through 125 ℃;
3) with step 1) gains and step 2) gains mix, and stir, and regulating pH value is 5.0, lyophilizing.
The effect that the present invention realizes is as follows:
The present invention earlier sodium tanshinone IIA sulfate or/and Tanshinone I I A sodium phosphate and native albumin are condensed into albumin millimicro ball.Because medicine is wrapped in intravasation by albumin, so reduce greatly in the pain on injection sense.Simultaneously, because albumin millimicro ball has targeting and oxidation resistance, reduced engulfing of macrophage owing to be coated on the PEG on albumin millimicro ball surface, thereby increased the stability of ingredient greatly, improved the valid density of ingredient, effectively prolonged the action time of medicine at patient part.The stability that hydroxypropyl methylcellulose that adds in the albumin millimicro ball glucose injection provided by the present invention and polygeline have increased solution has reduced sedimentary probability has taken place.Albumin millimicro ball lyophilized injection mean diameter provided by the invention has avoided the small particle diameter spheroid by the probability of hepatic clearance about 500nm.Albumin millimicro ball antigenicity provided by the present invention is little.
The specific embodiment
Embodiment 1:
Preparation medicine carrying millimicro ball is standby.
Fill a prescription following (by weight):
Albumin 1000-2000;
Tanshinone salt 20-200;
Vegetable oil 200000-400000;
PEG6000 100-200；
N-(2-mercapto radical propionyl group)-glycine 20-100;
Lysine hydrochloride 20-30.
1) it is soluble in water to get described amount albumin, make the albumin aqueous solution of 200g-300g/L, add described amount sodium tanshinone IIA sulfate or/and the tanshinone sodium phosphate, dissolving fully, add described amount lysine hydrochloride, PEG600 (Macrogol 600), N-(2-mercapto radical propionyl group)-glycine again, fully dissolving;
2) step 1) gained solution is added in the vegetable oil of described amount, stir 10-20 minute postcooling under the 100-120 ℃ of condition fast to room temperature;
3) the membrane filtration step 2 in usefulness 150nm aperture) gained solution obtains millimicro ball and filtrate, and the average 500nm of millimicro ball sphere diameter cleans lyophilization with cold diethyl ether;
4) with the membrane filtration step 3) gained filtrate in 50nm aperture, obtain the millimicro ball, sphere diameter 50-150nm cleans lyophilization with cold diethyl ether.
5) determination step 3 respectively) and the sodium tanshinone IIA sulfate in the step 4) gained millimicro ball or/and the content of tanshinone sodium phosphate.
Embodiment 2:
Preparation albumin millimicro ball glucose injection, fill a prescription following (in weight portion):
Albumin nanosphere medicine composition 10 in tanshinone salt;
Hydroxypropyl methylcellulose 20;
Polygeline 1250;
Antioxidant 40;
Glucose 12500
Water 250000.
Described antioxidant is meant the combination in any of reduced glutathion, cystine.
Concrete preparation method is as follows:
1) get particle diameter 50-150nm, contain the albumin nanosphere medicine composition of described amount tanshinone salt.
2) polygeline, antioxidant and the glucose of described amount joined in temperature 50-60 ℃ the water for injection of described amount, dissolving fully, regulating pH value is 5.0, with molecular cut off 10000 daltonian ultrafiltration post ultrafiltration, add described amount hydroxypropyl methylcellulose (before adding, handling 4 hours) in the ultrafiltrate, dissolving fully through 125 ℃.
3) with step 1) gains and step 2) gains mix, and stir, and regulating pH value is 5.0.
4) content of tanshinone salt in the mensuration medicine is distributed into 1000 by the pharmacy standard.
Adopting coronary heart disease, lung cancer model mice is laboratory animal, adopts albumin millimicro ball glucose injection provided by the present invention and sodium tanshinone IIA sulfate 5% glucose injection to compare experiment respectively.Experiment grouping: 100 laboratory animals of every group every kind disease, mice body weight 18-20g, intravenously administrable.
Usage and dosage:
Among each embodiment, the usage and dosage of albumin nanosphere medicine composition preparation was with reference to contrast experiment's usage and dosage after present embodiment reached.
By tanshinone salt weight be subjected to medicine mice weight ratio 40ug/kg, get above-mentioned injection and adopt the intravenous injection mode that experiment mice is carried out administration, be administered once every day, treatment cycle is 21 days, effect is as follows:
Embodiment 3:
Preparation albumin millimicro ball glucose injection, fill a prescription following (in weight portion):
Albumin nanosphere medicine composition 100 in tanshinone salt;
Hydroxypropyl methylcellulose 10;
Polygeline 2500;
Antioxidant 20;
Glucose 5000;
Water 250000.
Described antioxidant is meant a kind of or its combination in any in reduced glutathion, the cystine.
Albumin nanosphere medicine composition, hydroxypropyl methylcellulose, polygeline, antioxidant and the glucose mixed dissolution of described amount in the water of described amount, is distributed into 1000.
Concrete preparation method is as follows:
4) get particle diameter 50-150nm, contain the albumin nanosphere medicine composition of described amount tanshinone salt.
5) polygeline, antioxidant and the glucose of described amount joined in temperature 50-60 ℃ the water for injection of described amount, dissolving fully, regulating pH value is 5.0, with molecular cut off 10000 daltonian ultrafiltration post ultrafiltration, add described amount hydroxypropyl methylcellulose (before adding, handling 4 hours) in the ultrafiltrate, dissolving fully through 125 ℃.
6) with step 1) gains and step 2) gains mix, and stir, and regulating pH value is 5.0.
7) content of tanshinone salt in the mensuration medicine is distributed into 1000 by the pharmacy standard.
Adopting coronary heart disease, lung cancer model mice is laboratory animal, adopts albumin millimicro ball glucose injection provided by the present invention and sodium tanshinone IIA sulfate 5% glucose injection to compare experiment respectively.Experiment grouping: 100 laboratory animals of every group every kind disease, mice body weight 18-20g, intravenously administrable.
Usage and dosage:
By tanshinone salt weight be subjected to medicine mice weight ratio 40ug/kg, get above-mentioned injection and adopt the intravenous injection mode that experiment mice is carried out administration, be administered once every day, treatment cycle is 21 days, effect is as follows:
Embodiment 4:
Preparation albumin millimicro ball glucose injection, fill a prescription following (in weight portion):
Albumin nanosphere medicine composition 10 in tanshinone salt;
Hydroxypropyl methylcellulose 10;
Polygeline 1250;
Antioxidant 40;
Glucose 25000;
Water 250000.
Described antioxidant is meant a kind of or its combination in any in reduced glutathion, the cystine.
Albumin nanosphere medicine composition, hydroxypropyl methylcellulose, polygeline, antioxidant and the glucose mixed dissolution of described amount in the water of described amount, is distributed into 1000.
Concrete preparation method is as follows:
1) get particle diameter 50-150nm, contain the albumin nanosphere medicine composition of described amount tanshinone salt.
2) polygeline, antioxidant and the glucose of described amount joined in temperature 50-60 ℃ the water for injection of described amount, dissolving fully, regulating pH value is 5.0, with molecular cut off 10000 daltonian ultrafiltration post ultrafiltration, add described amount hydroxypropyl methylcellulose (before adding, handling 4 hours) in the ultrafiltrate, dissolving fully through 125 ℃.
3) with step 1) gains and step 2) gains mix, and stir, and regulating pH value is 5.0.
4) content of tanshinone salt in the mensuration medicine is distributed into 1000 by the pharmacy standard.
Adopting coronary heart disease, lung cancer model mice is laboratory animal, adopts albumin millimicro ball glucose injection provided by the present invention and sodium tanshinone IIA sulfate 5% glucose injection to compare experiment respectively.Experiment grouping: 100 laboratory animals of every group every kind disease, mice body weight 18-20g, intravenously administrable.
Usage and dosage:
By tanshinone salt weight be subjected to medicine mice weight ratio 40ug/kg, get above-mentioned injection and adopt the intravenous injection mode that experiment mice is carried out administration, be administered once every day, treatment cycle is 21 days, effect is as follows:
Embodiment 5:
Preparation albumin millimicro ball glucose injection, fill a prescription following (in weight portion):
Albumin nanosphere medicine composition 10 in tanshinone salt;
Hydroxypropyl methylcellulose 20;
Polygeline 2500;
Antioxidant 20;
Glucose 125000;
Water 250000.
Described antioxidant is meant a kind of or its combination in any in reduced glutathion, the cystine.
Albumin nanosphere medicine composition, hydroxypropyl methylcellulose, polygeline, antioxidant and the glucose mixed dissolution of described amount in the water of described amount, is distributed into 1000.
Concrete preparation method is as follows:
1) get particle diameter 50-150nm, contain the albumin nanosphere medicine composition of described amount tanshinone salt.
2) polygeline, antioxidant and the glucose of described amount joined in temperature 50-60 ℃ the water for injection of described amount, dissolving fully, regulating pH value is 5.0, with molecular cut off 10000 daltonian ultrafiltration post ultrafiltration, add described amount hydroxypropyl methylcellulose (before adding, handling 4 hours) in the ultrafiltrate, dissolving fully through 125 ℃.
3) with step 1) gains and step 2) gains mix, and stir, and regulating pH value is 5.0.
4) content of tanshinone salt in the mensuration medicine is distributed into 1000 by the pharmacy standard.
Adopting coronary heart disease, lung cancer model mice is laboratory animal, adopts albumin millimicro ball glucose injection provided by the present invention and sodium tanshinone IIA sulfate 5% glucose injection to compare experiment respectively.Experiment grouping: 100 laboratory animals of every group every kind disease, mice body weight 18-20g, intravenously administrable.
Usage and dosage:
Tanshinone salt weight be subjected to medicine mice weight ratio 40ug/kg, get above-mentioned injection and adopt the intravenous injection mode that experiment mice is carried out administration, be administered once every day, treatment cycle is 21 days, effect is as follows:
Embodiment 6:
Preparation is from albumen millimicro ball lyophilized injection, fill a prescription following (in weight portion):
Albumin nanosphere medicine composition 100 in tanshinone salt;
Hydroxypropyl methylcellulose 10;
Polygeline 60;
N-(2-mercapto radical propionyl group)-glycine/lysine hydrochloride 120;
Water 2000.
Concrete preparation method is as follows:
4) get particle diameter 500nm, contain the albumin nanosphere medicine composition of described amount tanshinone salt.
5) in the water for injection with the polygeline of described amount, described amount that N-(2-mercapto radical propionyl group)-glycine/lysine hydrochloride joins temperature 50-60 ℃; dissolving fully; regulating pH value is 5.0; with molecular cut off 10000 daltonian ultrafiltration post ultrafiltration; add described amount hydroxypropyl methylcellulose (before adding, handling 4 hours) in the ultrafiltrate, dissolving fully through 125 ℃.
6) with step 1) gains and step 2) gains mix, and stir, and regulating pH value is 5.0.
7) content of tanshinone salt in the mensuration medicine is distributed into 1000 by the pharmacy standard.
Adopting coronary heart disease, lung cancer model mice is laboratory animal, adopts albumin millimicro ball glucose injection provided by the present invention and sodium tanshinone IIA sulfate 5% glucose injection to compare experiment respectively.Experiment grouping: 100 laboratory animals of every group every kind disease, mice body weight 18-20g, intravenously administrable.
Usage and dosage:
Among each embodiment, the usage and dosage of albumin nanosphere medicine composition preparation was with reference to contrast experiment's usage and dosage after present embodiment reached.
By tanshinone salt weight be subjected to medicine mice weight ratio 40ug/kg, get above-mentioned albumin millimicro ball lyophilized injection and adopt the intravenous injection mode that experiment mice is carried out administration, be administered once every day, treatment cycle is 21 days, effect is as follows:
Embodiment 7:
Preparation albumin millimicro ball lyophilized injection, fill a prescription following (in weight portion):
Albumin nanosphere medicine composition 10 in tanshinone salt;
Hydroxypropyl methylcellulose 10;
Polygeline 60;
N-(2-mercapto radical propionyl group)-glycine/lysine hydrochloride 120;
Water 2000.
Concrete preparation method is as follows:
1) get particle diameter 500nm, contain the albumin nanosphere medicine composition of described amount tanshinone salt.
2) in the water for injection with the polygeline of described amount, described amount that N-(2-mercapto radical propionyl group)-glycine/lysine hydrochloride joins temperature 50-60 ℃; dissolving fully; regulating pH value is 5.0; with molecular cut off 10000 daltonian ultrafiltration post ultrafiltration; add described amount hydroxypropyl methylcellulose (before adding, handling 4 hours) in the ultrafiltrate, dissolving fully through 125 ℃.
3) with step 1) gains and step 2) gains mix, and stir, and regulating pH value is 5.0.
4) content of tanshinone salt in the mensuration medicine is distributed into 1000 by the pharmacy standard.
Adopting coronary heart disease, lung cancer model mice is laboratory animal, adopts albumin millimicro ball glucose injection provided by the present invention and sodium tanshinone IIA sulfate 5% glucose injection to compare experiment respectively.Experiment grouping: 100 laboratory animals of every group every kind disease, mice body weight 18-20g, intravenously administrable.
Usage and dosage:
By tanshinone salt weight be subjected to medicine mice weight ratio 40ug/kg, get above-mentioned albumin millimicro ball lyophilized injection and adopt the intravenous injection mode that experiment mice is carried out administration, be administered once every day, treatment cycle is 21 days, effect is as follows:
Embodiment 8:
Preparation albumin millimicro ball lyophilized injection, fill a prescription following (in weight portion):
Albumin nanosphere medicine composition 100 in tanshinone salt;
Hydroxypropyl methylcellulose 10;
Polygeline 60;
N-(2-mercapto radical propionyl group)-glycine/lysine hydrochloride 60;
Water 2000.
Concrete preparation method is as follows:
Get particle diameter 500nm, contain the albumin nanosphere medicine composition of described amount tanshinone salt.
1) in the water for injection with the polygeline of described amount, described amount that N-(2-mercapto radical propionyl group)-glycine/lysine hydrochloride joins temperature 50-60 ℃; dissolving fully; regulating pH value is 5.0; with molecular cut off 10000 daltonian ultrafiltration post ultrafiltration; add described amount hydroxypropyl methylcellulose (before adding, handling 4 hours) in the ultrafiltrate, dissolving fully through 125 ℃.
2) with step 1) gains and step 2) gains mix, and stir, and regulating pH value is 5.0.
3) content of tanshinone salt in the mensuration medicine is distributed into 1000 by the pharmacy standard.
Adopting coronary heart disease, lung cancer model mice is laboratory animal, adopts albumin millimicro ball glucose injection provided by the present invention and sodium tanshinone IIA sulfate 5% glucose injection to compare experiment respectively.Experiment grouping: 100 laboratory animals of every group every kind disease, mice body weight 18-20g, intravenously administrable.
Usage and dosage:
By tanshinone salt weight be subjected to medicine mice weight ratio 40ug/kg, get above-mentioned albumin millimicro ball lyophilized injection and adopt the intravenous injection mode that experiment mice is carried out administration, be administered once every day, treatment cycle is 21 days, effect is as follows:
Embodiment 9:
Preparation albumin millimicro ball lyophilized injection, fill a prescription following (in weight portion):
Albumin nanosphere medicine composition 10 in tanshinone salt;
Hydroxypropyl methylcellulose 20;
Polygeline 50;
N-(2-mercapto radical propionyl group)-glycine/lysine hydrochloride 120;
Water 2000.
Concrete preparation method is as follows:
1) get particle diameter 500nm, contain the albumin nanosphere medicine composition of described amount tanshinone salt.
2) in the water for injection with the polygeline of described amount, described amount that N-(2-mercapto radical propionyl group)-glycine/lysine hydrochloride joins temperature 50-60 ℃; dissolving fully; regulating pH value is 5.0; with molecular cut off 10000 daltonian ultrafiltration post ultrafiltration; add described amount hydroxypropyl methylcellulose (before adding, handling 4 hours) in the ultrafiltrate, dissolving fully through 125 ℃.
3) with step 1) gains and step 2) gains mix, and stir, and regulating pH value is 5.0.
4) content of tanshinone salt in the mensuration medicine is distributed into 1000 by the pharmacy standard.
Adopting coronary heart disease, lung cancer model mice is laboratory animal, adopts albumin millimicro ball glucose injection provided by the present invention and sodium tanshinone IIA sulfate 5% glucose injection to compare experiment respectively.Experiment grouping: 100 laboratory animals of every group every kind disease, mice body weight 18-20g, intravenously administrable.
Usage and dosage:
By tanshinone salt weight be subjected to medicine mice weight ratio 40ug/kg, get above-mentioned albumin millimicro ball lyophilized injection and adopt the intravenous injection mode that experiment mice is carried out administration, be administered once every day, treatment cycle is 21 days, effect is as follows:
Claims (10)
1. albumin nanosphere medicine composition, it is characterized in that: the feedstock production by following parts by weight forms:
Albumin 1000-2000;
Tanshinone salt 20-200;
Vegetable oil 200000-400000;
PEG6000 100-200；
N-(2-mercapto radical propionyl group)-glycine 20-100;
Lysine hydrochloride 20-30.
2. according to the described albumin nanosphere medicine composition of claim 1, it is characterized in that: described albumin is meant the combination in any in zein, bovin serum albumin, the egg albumen.
3. according to the described albumin nanosphere medicine composition of claim 1, it is characterized in that: described tanshinone salt is meant the combination in any of sodium tanshinone IIA sulfate, tanshinone sodium phosphate.
4. according to the described albumin nanosphere medicine composition of claim 1, it is characterized in that: described vegetable oil is meant the combination in any of Semen Maydis oil, Oleum sesami, soybean oil.
5. the described albumin nanosphere medicine composition preparation method of claim 1 is characterized in that: comprise the steps:
1) it is soluble in water to get described amount albumin, make the albumin aqueous solution of 200g-300g/L, add described amount sodium tanshinone IIA sulfate or/and the tanshinone sodium phosphate, dissolving fully, add described amount lysine hydrochloride, PEG600 (Macrogol 600), N-(2-mercapto radical propionyl group)-glycine again, fully dissolving;
2) step 1) gained solution is added in the vegetable oil of described amount, stir 10-20 minute postcooling under the 100-120 ℃ of condition fast to room temperature;
3) the membrane filtration step 2 in usefulness 150nm aperture) gained solution obtains millimicro ball and filtrate, and the average 500nm of millimicro ball sphere diameter cleans lyophilization with cold diethyl ether;
4) with the membrane filtration step 3) gained filtrate in 50nm aperture, obtain the millimicro ball, sphere diameter 50-150nm cleans lyophilization with cold diethyl ether.
6. utilize the albumin millimicro ball glucose injection of the described albumin nanosphere medicine composition preparation of claim 1, it is characterized in that: the feedstock production by following parts by weight forms:
Albumin nanosphere medicine composition 10-100 in tanshinone salt;
Hydroxypropyl methylcellulose 10-20;
Polygeline 1250-2500;
Antioxidant 20-40;
Glucose 12500-25000
Water 250000.
7. according to the described albumin millimicro of claim 6 ball glucose injection, it is characterized in that: described antioxidant is meant a kind of or its combination in any in reduced glutathion, the cystine.
8. according to the described albumin millimicro of claim 6 ball glucose injection, it is characterized in that: preparation method is as follows:
1) gets the albumin nanosphere medicine composition that contains described amount tanshinone salt;
2) polygeline, antioxidant and the glucose of described amount joined in temperature 50-60 ℃ the water for injection of described amount, dissolving fully, regulating pH value is 5.0, with molecular cut off 10000 daltonian ultrafiltration post ultrafiltration, add described amount hydroxypropyl methylcellulose (before adding, handling 4 hours) in the ultrafiltrate, dissolving fully through 125 ℃;
3) with step 1) gains and step 2) gains mix, and stir, and regulating pH value is 5.0.
9. utilize the albumin millimicro ball lyophilized injection of the described albumin nanosphere medicine composition preparation of claim 1, it is characterized in that: the feedstock production by following parts by weight forms:
Albumin nanosphere medicine composition 10-100 in tanshinone salt;
Hydroxypropyl methylcellulose 10-20;
Polygeline 50-60;
N-(2-mercapto radical propionyl group)-glycine/lysine hydrochloride 60-120;
Water 2000.
10. according to the described albumin millimicro of claim 9 ball lyophilized injection, it is characterized in that: preparation method is as follows:
1) gets the albumin nanosphere medicine composition that contains described amount tanshinone salt;
2) in the water for injection with the polygeline of described amount, described amount that N-(2-mercapto radical propionyl group)-glycine/lysine hydrochloride joins temperature 50-60 ℃, dissolving fully, regulating pH value is 5.0, with molecular cut off 10000 daltonian ultrafiltration post ultrafiltration, add described amount hydroxypropyl methylcellulose (before adding, handling 4 hours) in the ultrafiltrate, dissolving fully through 125 ℃;
3) with step 1) gains and step 2) gains mix, and stir, and regulating pH value is 5.0, lyophilizing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006100808432A CN1843504B (en) | 2006-05-18 | 2006-05-18 | Albumin nanosphere medicine composition and its preparation method and application method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006100808432A CN1843504B (en) | 2006-05-18 | 2006-05-18 | Albumin nanosphere medicine composition and its preparation method and application method |
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| Publication Number | Publication Date |
|---|---|
| CN1843504A true CN1843504A (en) | 2006-10-11 |
| CN1843504B CN1843504B (en) | 2011-12-07 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019245073A1 (en) * | 2018-06-20 | 2019-12-26 | 주식회사 디오스템스 | Antioxidant composition |
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2006
- 2006-05-18 CN CN2006100808432A patent/CN1843504B/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019245073A1 (en) * | 2018-06-20 | 2019-12-26 | 주식회사 디오스템스 | Antioxidant composition |
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| Publication number | Publication date |
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| CN1843504B (en) | 2011-12-07 |
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