CN101152178B - Sophoridine nano liposome medicament and preparation of the same - Google Patents
Sophoridine nano liposome medicament and preparation of the same Download PDFInfo
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- CN101152178B CN101152178B CN2007101757377A CN200710175737A CN101152178B CN 101152178 B CN101152178 B CN 101152178B CN 2007101757377 A CN2007101757377 A CN 2007101757377A CN 200710175737 A CN200710175737 A CN 200710175737A CN 101152178 B CN101152178 B CN 101152178B
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Abstract
The invention relates to a sophoridine nanoliposome drug and the preparation method. The invention provides a sophoridine nanoliposome drug and the material and the content of the material are as follows: 350-500 compound of HSPC for injection and Vitamin E with a mass ration 9.8: 0.2; 20 to 30 compound of cholesterol and Beta-sitosterol with a mass ratio 1 to 3:1; sophoridine 10 to 25; 125 to 200 compound of dextran 40 and mannitol with a mass ratio 1: 7 to 9; 5 to 10reduced glutathione; and poloxamer F-6835-40. The invention also provides the preparation method of the sophoridine nanoliposome. The drug provided in the invention can be used to treat adenocarcinoma, inflammation, gout, progressive disease of the central nervous system, to relieve pain and treat viral myocarditis.
Description
Technical field
The present invention relates to sophoridine nano liposome medicament and preparation thereof.
Background technology
Sophoridine (sophocarine), molecular formula C
15H
24N
2O, molecular weight 248 is a kind of alkaloids that extract from the leguminous plant Herba Sophorae alopecuroidis.
Existing sophoridine preparation technique has been realized the leap from the Herba Sophorae alopecuroidis extract of complexity to the effective monomer medicine, can be used for preparation treatment adenocarcinoma, antiinflammatory, gout, anti-nervus centralis degenerative disorders, analgesia and viral myocarditis medicine.Adenocarcinoma is meant with the body of gland to be the cancer that the basis takes place, and comprises breast carcinoma, nasopharyngeal carcinoma, pulmonary carcinoma, carcinoma of tongue, esophageal carcinoma, gastric cancer, intestinal cancer, hepatocarcinoma, cervical cancer etc.But, the sophoridine preparation of prior art toxic and side effects control aspect not satisfactory, exist also that gastrointestinal tract is felt sick, the untoward reaction such as neurotoxicity when vomiting and dosage are big.
Summary of the invention
In order to solve the problem that there is above-mentioned untoward reaction in existing sophoridine preparation, the invention provides a kind of nano liposome medicament of sophoridine, can be used for preparation treatment adenocarcinoma, antiinflammatory, gout, anti-nervus centralis degenerative disorders, analgesia and viral myocarditis medicine.Adenocarcinoma is meant with the body of gland to be the cancer that the basis takes place, and comprises breast carcinoma, nasopharyngeal carcinoma, pulmonary carcinoma, carcinoma of tongue, esophageal carcinoma, gastric cancer, intestinal cancer, hepatocarcinoma, cervical cancer etc.
Technical scheme of the present invention is as follows:
The invention provides a kind of sophoridine nano liposome medicament, raw materials used and parts by weight are as follows:
Injection hydrogenated soy phosphatidyl choline and vitamin E
9.8: 0.2 mixture 350-500 of weight ratio;
Cholesterol and cupreol weight ratio 1-3: 1 mixture 20-30;
Sophoridine 10-25;
The mixture 125-200 of dextran-40 and mannitol weight ratio 1: 7-9;
Reduced glutathion 5-10;
Poloxamer F-68 35-40.
The present invention also provides the preparation method of sophoridine nanoliposome, comprises the steps:
(4) successively with sophoridine, injection hydrogenated soy phosphatidyl choline and 9.8: 0.2 mixture of vitamin E weight ratio, cholesterol and cupreol weight ratio 1-3: 1 mixture is dissolved in ether and ethanol volume ratio 3-5: in 1 the mixed liquor, remove ether and ethanol under reduced pressure under 30-40 ℃ of condition in the Rotary Evaporators, form liposome membrane at the bottle wall;
(5) successively mixture, reduced glutathion and the poloxamer F-68 of dextran-40 and mannitol weight ratio 1: 7-9 is dissolved in the phosphate buffer, 20 minutes steam sterilizations under 121 ℃ of conditions, being chilled to and regulating pH value after the room temperature is 6.0-7.0;
(6) the liposome membrane ether dissolution that step (1) is made, in the auxiliary material liquid of the phosphate buffer that adding step (2) makes, and in high speed shear emulsifying dispersion machine under the vacuum, 1200rpm emulsifying disperses more than 5 minutes, 30-35 ℃ of reduction vaporization eliminates ether then, difference filters 4-6 time through the nucleopore membranes of 1.0 μ m, 0.08 μ m, 0.05 μ m successively in the high pressure thrashing machine, makes the nanoparticle liposome medicament.
Above-mentioned nano liposome medicament is made acceptable lyophilized injection on the pharmaceutics, oral formulations, spray, bulk capacity injection, small-volume injection or multi-chamber-bag injection by the pharmacopedics conventional method.
The technique effect that the present invention realizes is as follows:
(1) medicine of the present invention belongs to natural drug monomer liposome targeting preparation;
(2) there is not the difficulty of finger printing in medicine of the present invention;
(3) medicine of the present invention is made nanometer liposome, and particle size is fit to merge with tumor cell and discharge medicine just in time by tumor blood capillary gap, has reduced medicine invalid loss in vivo greatly, thereby the little curative effect height of dosage;
(4) medicine of the present invention is made macrocyclic liposome medicament, avoids engulfing of reticuloendothelial system, and more multiple medicines thing, more time arrive targeting moiety, have reduced the medication number of times;
(5) medicine of the present invention be that dosage is little, curative effect is high, long action time, medicine that toxic and side effects is low;
(6) medicine of the present invention is a long circulating liposomes, does not have medicine burst effect in vivo, has avoided the generation of the instant toxic and side effects of medicine;
(7) medicine of the present invention is added with antioxidant glutathion and vitamin E, avoided phospholipid and medicine in vivo and in vitro peroxidating and produce toxic and side effects;
Again dissolve when (8) lyophilized injection of medicine of the present invention uses, can not condense, layering and drug leakage incident;
(9) preparation technology of medicine of the present invention is simple, and product is aseptic, and thermal source only is 1/4th of a prior art medicine, and impurity and related substances only are 1/5th of prior art medicine, and effect duration is more than 1.5 times of prior art medicine;
(10) curative effect of medication height of the present invention, quality is good, and stability is strong.
The specific embodiment
Embodiment 1:
Present embodiment adopts sophoridine nano liposome medicament prescription as follows:
Injection hydrogenated soy phosphatidyl choline and vitamin E
9.8: 0.2 mixture 350g of weight ratio;
1: 1 mixture 30g of cholesterol and cupreol weight ratio;
Sophoridine 10g;
1: 7 mixture 200g of dextran-40 and mannitol weight ratio;
Reduced glutathion 5g;
Poloxamer F-68 40g;
Phosphate buffer (0.01M, PH6.0-7.0) 2000g.
Preparation method is as follows:
(1) successively with sophoridine, injection hydrogenated soy phosphatidyl choline and 9.8: 0.2 mixture of vitamin E weight ratio, cholesterol and cupreol weight ratio 1-3: 1 mixture is dissolved in ether and ethanol volume ratio 3-5: in 1 the mixed liquor, remove ether and ethanol under reduced pressure under 30-40 ℃ of condition in the Rotary Evaporators, form liposome membrane at the bottle wall;
(2) successively mixture, reduced glutathion and the poloxamer F-68 of dextran-40 and mannitol weight ratio 1: 7-9 is dissolved in the phosphate buffer, 20 minutes steam sterilizations under 121 ℃ of conditions, being chilled to and regulating pH value after the room temperature is 6.0-7.0;
(3) the liposome membrane ether dissolution that step (1) is made, in the auxiliary material liquid of the phosphate buffer that adding step (2) makes, and in high speed shear emulsifying dispersion machine under the vacuum, 1200rpm emulsifying disperses more than 5 minutes, 30-35 ℃ of reduction vaporization eliminates ether then, difference filters 4-6 time through the nucleopore membranes of 1.0 μ m, 0.08 μ m, 0.05 μ m successively in the high pressure thrashing machine, makes the nanoparticle liposome medicament.
The pharmacodynamics confirmatory experiment:
Rat liver cancer model, the treatment group is the lyophilized injection of medicine of the present invention, divides 7.5mg/kg, 10mg/kg, three kinds of dosage groups of 12.5mg/kg, matched group is the light water injection of 25mg/kg dosage, every group of 30 mices.Carry out the tail vein injection administration.Be administered once in per three days, administration after 21 days statistical result as follows:
Embodiment 2:
Present embodiment adopts sophoridine nano liposome medicament prescription as follows:
Injection hydrogenated soy phosphatidyl choline and vitamin E
9.8: 0.2 mixture 500g of weight ratio;
3: 1 mixture 20g of cholesterol and cupreol weight ratio;
Sophoridine 25g;
1: 9 mixture 125g of dextran-40 and mannitol weight ratio;
Reduced glutathion 10g;
Poloxamer F-68 35g;
Phosphate buffer (0.01M, PH6.0-7.0) 1750g.
Preparation method is the same.
The pharmacodynamics confirmatory experiment:
Rat liver cancer model, the treatment group is the lyophilized injection of medicine of the present invention, divides 7.5mg/kg, 10mg/kg, three kinds of dosage groups of 12.5mg/kg, matched group is the light water injection of 25mg/kg dosage, every group of 30 mices.Carry out the tail vein injection administration.Be administered once in per three days, administration after 21 days statistical result as follows:
Embodiment 3:
Present embodiment adopts sophoridine nano liposome medicament prescription as follows:
Injection hydrogenated soy phosphatidyl choline and vitamin E
9.8: 0.2 mixture 350g of weight ratio;
1: 1 mixture 20g of cholesterol and cupreol weight ratio;
Sophoridine 10g;
1: 7 mixture 125g of dextran-40 and mannitol weight ratio;
Reduced glutathion 5g;
Poloxamer F-68 35g;
Phosphate buffer (0.01M, PH6.0-7.0) 1750g.
Preparation method is the same.
The pharmacodynamics confirmatory experiment:
Rat liver cancer model, the treatment group is the lyophilized injection of medicine of the present invention, divides 7.5mg/kg, 10mg/kg, three kinds of dosage groups of 12.5mg/kg, matched group is the light water injection of 25mg/kg dosage, every group of 30 mices.Carry out the tail vein injection administration.Be administered once in per three days, administration after 21 days statistical result as follows:
Embodiment 4:
Present embodiment adopts sophoridine nano liposome medicament prescription as follows:
Injection hydrogenated soy phosphatidyl choline and vitamin E
9.8: 0.2 mixture 350g of weight ratio;
3: 1 mixture 30g of cholesterol and cupreol weight ratio;
Sophoridine 25g;
1: 9 mixture 200g of dextran-40 and mannitol weight ratio;
Reduced glutathion 10g;
Poloxamer F-68 40g;
Phosphate buffer (0.01M, PH6.0-7.0) 2000g.
Preparation method is the same.
The pharmacodynamics confirmatory experiment:
Rat liver cancer model, the treatment group is the lyophilized injection of medicine of the present invention, divides 7.5mg/kg, 10mg/kg, three kinds of dosage groups of 12.5mg/kg, matched group is the light water injection of 25mg/kg dosage, every group of 30 mices.Carry out the tail vein injection administration.Be administered once in per three days, administration after 21 days statistical result as follows:
Embodiment 5:
Present embodiment adopts sophoridine nano liposome medicament prescription as follows:
Injection hydrogenated soy phosphatidyl choline and vitamin E
9.8: 0.2 mixture 480g of weight ratio;
2: 1 mixture 23g of cholesterol and cupreol weight ratio;
Sophoridine 18g;
1: 8 mixture 169g of dextran-40 and mannitol weight ratio;
Reduced glutathion 8g;
Poloxamer F-68 37g;
Phosphate buffer (0.01M, PH6.0-7.0) 1860g.
Preparation method is the same.
The pharmacodynamics confirmatory experiment:
Rat liver cancer model, the treatment group is the lyophilized injection of medicine of the present invention, divides 7.5mg/kg, 10mg/kg, three kinds of dosage groups of 12.5mg/kg, matched group is the light water injection of 25mg/kg dosage, every group of 30 mices.Carry out the tail vein injection administration.Be administered once in per three days, administration after 21 days statistical result as follows:
According to above-mentioned experimental result as can be seen, medicine of the present invention possesses good prospects for application.
Claims (2)
1. sophoridine nano liposome medicament, by the raw material of following parts by weight:
Injection hydrogenated soy phosphatidyl choline and vitamin E
9.8: 0.2 mixture 350-500 of weight ratio,
Cholesterol and cupreol weight ratio 1-3: 1 mixture 20-30,
Sophoridine 10-25,
The mixture 125-200 of dextran-40 and mannitol weight ratio 1: 7-9,
Reduced glutathion 5-10,
Poloxamer F-68 35-40;
Be prepared from by following step:
(1) successively with sophoridine, injection hydrogenated soy phosphatidyl choline and 9.8: 0.2 mixture of vitamin E weight ratio, cholesterol and cupreol weight ratio 1-3: 1 mixture is dissolved in ether and ethanol volume ratio 3-5: in 1 the mixed liquor, remove ether and ethanol under reduced pressure under 30-40 ℃ of condition in the Rotary Evaporators, form liposome membrane at the bottle wall
(2) successively mixture, reduced glutathion and the poloxamer F-68 of dextran-40 and mannitol weight ratio 1: 7-9 is dissolved in the phosphate buffer, 20 minutes steam sterilizations under 121 ℃ of conditions, being chilled to and regulating pH value after the room temperature is 6.0-7.0,
(3) the liposome membrane ether dissolution that step (1) is made, in the auxiliary material liquid of the phosphate buffer that adding step (2) makes, and in high speed shear emulsifying dispersion machine under the vacuum, 1200rpm emulsifying disperses more than 5 minutes, 30-35 ℃ of reduction vaporization eliminates ether then, difference filters 4-6 time through the nucleopore membranes of 1.0 μ m, 0.08 μ m, 0.05 μ m successively in the high pressure thrashing machine, makes the nanoparticle liposome medicament.
2. acceptable lyophilized injection, oral formulations, spray, bulk capacity injection, small-volume injection or multi-chamber-bag injection on the pharmaceutics made of the described nano liposome medicament of claim 1.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2007101757377A CN101152178B (en) | 2007-10-11 | 2007-10-11 | Sophoridine nano liposome medicament and preparation of the same |
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| CN2007101757377A CN101152178B (en) | 2007-10-11 | 2007-10-11 | Sophoridine nano liposome medicament and preparation of the same |
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| CN101152178B true CN101152178B (en) | 2010-10-06 |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101912363A (en) * | 2010-07-29 | 2010-12-15 | 蔡海德 | Dissolving ultrafiltration-spray drying-molecule dispersion coating-hydration palletizing-freeze drying method for preparing liposome combination medicine |
| WO2018007878A1 (en) * | 2016-07-05 | 2018-01-11 | CanTrust LifeScience Corp. | Methods of treating and preventing gout and lead nephropathy |
| CN106361710B (en) * | 2016-08-29 | 2019-03-05 | 海南合瑞制药股份有限公司 | A kind of milrinone lactate composition |
| CN107669672A (en) * | 2017-10-11 | 2018-02-09 | 中国科学院西北高原生物研究所 | Application and its medicine of the Sophoridine in osteosporosis resistant medicament is prepared |
| CN113967192A (en) * | 2021-11-09 | 2022-01-25 | 陕西海斯夫生物工程有限公司 | Pharmaceutical composition for accelerating wound healing, preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1343490A (en) * | 2001-06-14 | 2002-04-10 | 通化方大药业股份有限公司 | Sophoridine and its application in analgesic |
| CN1887271A (en) * | 2006-08-02 | 2007-01-03 | 刘祥华 | Azithromycin liposome composition medicine and its prepn process |
| CN101019869A (en) * | 2007-03-09 | 2007-08-22 | 蔡海德 | Medicine composition of alprostadil and Chuanhuning/Yanhuning liposome and its prepn |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1343490A (en) * | 2001-06-14 | 2002-04-10 | 通化方大药业股份有限公司 | Sophoridine and its application in analgesic |
| CN1887271A (en) * | 2006-08-02 | 2007-01-03 | 刘祥华 | Azithromycin liposome composition medicine and its prepn process |
| CN101019869A (en) * | 2007-03-09 | 2007-08-22 | 蔡海德 | Medicine composition of alprostadil and Chuanhuning/Yanhuning liposome and its prepn |
Non-Patent Citations (1)
| Title |
|---|
| CN 1887271 A,全文. |
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Owner name: JIANGSU DELUN BIOPHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: CAI HAIDE Effective date: 20120524 |
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Effective date of registration: 20120524 Address after: 330009, room 11, 201 Bai Yi, Xiangshan South Road, Jiangxi, Nanchang Patentee after: Jiangsu Deren Biological Pharmaceutical Co Ltd Address before: 330009, room 11, 201 Bai Yi, Xiangshan South Road, Nanchang, Jiangxi, Xihu District Patentee before: Cai Haide |
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