CN1253832A - Metabolism-supporting preparation for curing hepatic failure and its preparation method - Google Patents
Metabolism-supporting preparation for curing hepatic failure and its preparation method Download PDFInfo
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- CN1253832A CN1253832A CN 99125265 CN99125265A CN1253832A CN 1253832 A CN1253832 A CN 1253832A CN 99125265 CN99125265 CN 99125265 CN 99125265 A CN99125265 A CN 99125265A CN 1253832 A CN1253832 A CN 1253832A
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Abstract
The present invention belongs to a medicine preparation for curing acute severe hepatitis and fulminant hepatic failure, in particular it relates to a hepatic failure metabolism supporting agent for patient with fulminant hepatic failure and its preparation method. It utilizes synthetic or natural membrane material to embed or microcapsulize the enzyme system which partically participates in detoxification function of hepatic cells to obtain microspheres or microcapsules, and the diameter of said particle is 1-200 micrometers. Said important enzyme system and low molecular substance possess the detoxification function of hepatic cells, and can be injected into the body fluid of the patient or implement external dialysis to participate in hepatic activity to produce detoxification function, and can eliminate the toxin produced by necrotic tissue of hepatic cells.
Description
The invention belongs to a kind of medicament for the treatment of acute serious hepatitis and fulminant hepatic failure, particularly a kind of to fulminant liver patient's the liver metabolism proppant and preparation method thereof that declines that declines.
The fulminant liver declines and causes large tracts of land hepatic necrosis or hepatocyte inner cell organ severe dysfunction by a variety of causes and cause the disease of the serious dysbolismus of body, can develop rapidly to hepatic encephalopathy, and its mortality rate is high.Current treatment means mainly is to rely on the internal medicine nursing and by the artifical liver support system, and the toxicant in the blood samples of patients is adsorbed and dialyses.After the liver failure, a large amount of hepatic necrosis, hepatocyte is lost its physiological detoxication function, and downright bad hepatocyte becomes new toxin again in patient's body.And the artifical liver support system can only substitute downright bad hepatocellular function, but can not eliminate the toxin that downright bad hepatocyte produces.The present invention is directed to compound enzyme and have Detoxication for the liver toxin that is produced that declines; but can not be directly and body fluid carry out reaction properties; for metastable environment is made in compound enzyme performance Detoxication; protease molecule, lower-molecular substance and the stable protective agent that reaches are carried out embedding; make the liver metabolism proppant that declines, eliminated the toxin of hepatic necrosis tissue effectively.
The objective of the invention is to utilize synthetic or natural membranes material, the enzyme system of subparticipation hepatocyte function of detoxification is carried out embedding or microencapsulation, make microsphere or microcapsule, its particle diameter is the 1-200 micron, its important enzyme system and lower-molecular substance participate in the liver activity and have function of detoxification, and eliminate the toxin that the hepatic necrosis tissue produces.
Technical scheme of the present invention realizes by following pharmaceutical formulation and preparation method.
The liver metabolism proppant that declines, its preparation is formed the decline mother solution of metabolism proppant of fulminant liver by the multienzyme complex of protease such as enzyme molecule and coenzyme, lower-molecular substance with as albumin, the serum albumin buffer of enzyme stabilizers, utilize synthetic or made mother solution is carried out embedding to natural biological membrane material substep or microencapsulation is handled, the microencapsulated form liver of making diameter and be the 1-200 micron metabolism proppant that declines.
Fulminant liver its concrete pharmaceutical formulation of metabolism proppant following (is example with 100g dosage) that declines
(1) glutathione peroxidase: 1.0g
(2) glutathione-S-transferase: 2.0g
(3) G-6-P deoxygenase: 1.0g
(4) glutathion (oxidized form): 5.0g
(5) glutathion (reduced form): 2.5g
(6) glutathion reductase: 1.0g
(7) G-6-P: 3.0g
(8) coenzyme II (oxidized form): 0.2g
(9) coenzyme II (reduced form): 2.0g
(10) UDP-glucuronyl transferase: 1.0g
(11) albumin (or serum albumin): 10.0g
(12) buffer agent: 71.3g
The preparation of above preparation comprises following four steps:
One, manufacturing contains multienzyme complex Na-alginate mother solution, be A liquid: contain multienzyme complex with glutathione peroxidase, glutathione-S-transferase, G-6-P deoxygenase, glutathion (oxidized form), glutathion (reduced form), glutathion reductase, G-6-P, coenzyme II (oxidized form), coenzyme II (reduced form), UDP-glucuronyl transferase etc., preparation contains multienzyme complex Na-alginate mother solution, the basic mother solution of proceed step by step embedding after being made for;
Two, preparation lipid membrane, i.e. B liquid: phospholipid is dissolved in the chloroform, puts into the circular glass vessel, heated volatile forms lipid membrane.Make B liquid;
Three, preparation contains multienzyme complex liposome microsphere and microcapsule:
(1) system contains multienzyme complex liposome microsphere, i.e. C liquid: get A liquid, B liquid is put into ultrasonic device, carries out supersound process, or carry out sucking filtration repeatedly at the G4-G6 glass filter, form diameter 1-200 micron, with the solid microsphere of lipid membrane embedding.Make C liquid;
(2) system contains the Na-alginate microsphere of multienzyme complex, be D liquid: C liquid is put into contained 10% (W/V) calcium chloride solution, under the 4C temperature, preserve 12 hours centrifugal then rejects and fall the supernatant, its precipitate is with the solid microsphere of lipid membrane embedding, promptly contain multienzyme complex Na-alginate microsphere, make D liquid;
(3) system contains the Na-alginate-polylysine microsphere of multienzyme complex, be E liquid: after placing 1.0% calcium chloride solution of 0.1%CHES to place 3-10 minute D liquid, be placed on again in the polylysine solution that contains 0.1%-0.5% 10-30 minute, formation is with the solid microsphere of lipid membrane embedding, promptly contain the Na-alginate polylysine microsphere of multienzyme complex, make E liquid;
(4) system contains the Na-alginate-polylysine-Na-alginate microsphere of multienzyme complex, be F liquid: the E liquid of making was put into 0.5-1.5% (W/V) Na-alginate solution 5-10 minute, formation is with the solid microsphere of lipid membrane embedding, promptly contain the Na-alginate-polylysine-Na-alginate microsphere of multienzyme complex, make F liquid;
(5) system contains the Na-alginate-polylysine-Na-alginate microcapsule of multienzyme complex, be G liquid: with F liquid put into the 10-80MM citric acid receive liquid 5-10 minute (perhaps using the EDTA liquid of 20-100MM) liquefaction Na-alginate-polylysine-Na-alginate microsphere, make microcapsule with lipid membrane embedding liquid, make G liquid, i.e. the liver metabolism proppant that declines;
Four, finished product and preservation: with the G liquid of making, promptly the liver metabolism proppant that declines is placed in the enzyme stabilizers that contains albumin or serum albumin buffer agent and preserves.
Be example explanation embodiments of the invention now with the preparation 100g liver metabolism proppant that declines:
The decline preparation flow figure of metabolism proppant of Fig. 1 liver:
A kind of liver its pharmaceutical formulation of metabolism proppant that declines is:
(1) glutathione peroxidase: 1.0g
(2) glutathione-S-transferase: 2.0g
(3) G-6-P deoxygenase: 1.0g
(4) glutathion (oxidized form): 5.0g
(5) glutathion (reduced form): 2.5g
(6) glutathion reductase: 1.0g
(7) G-6-P: 3.0g
(8) coenzyme II (oxidized form): 0.2g
(9) coenzyme II (reduced form): 2.0g
(10) UDP-glucuronyl transferase: 1.0g
(11) albumin (or serum albumin): 10.0g
(12) buffer agent: 71.3g
The decline preparation process of metabolism proppant of liver is:
One, manufacturing contains multienzyme complex Na-alginate mother solution, be A liquid: with glutathione peroxidase 1g, glutathione-S-transferase 2g, G-6-P deoxygenase 1g, glutathion (oxidized form) 5g, glutathion (reduced form) 2.5g, glutathion reductase 1g, G-6-P 3g, coenzyme II (oxidized form) 0.2g, coenzyme II (reduced form) 2g, UDP-glucuronyl transferase 1g etc. contains multienzyme complex and as protectant albumin (or serum albumin) 10g, buffer agent 71.3g makes and contains multienzyme complex Na-alginate mother solution (being A liquid), the basic mother solution of proceed step by step embedding after being made for;
Two, preparation lipid membrane, i.e. B liquid: phospholipid is dissolved in the chloroform, puts into the circular glass vessel, heated volatile forms lipid membrane.Getting A liquid is placed on and carries out aquation in the lipid membrane and form how precious microcapsule and make B liquid;
Three, preparation contains multienzyme complex liposome microsphere, be C liquid: get A liquid and be placed on and carry out aquation in the lipid membrane and form the multicell microcapsule, A liquid, B liquid side are gone in the ultrasonic device, carry out supersound process, or carry out sucking filtration repeatedly at the G4-G6 glass filter, form diameter 1-200 micron, make C liquid with the microcapsule of lipid membrane embedding liquid;
Four, system contains the Na-alginate microsphere of multienzyme complex, be D liquid: C liquid is put into contained 10% (W/V) calcium chloride solution, under the 4C temperature, preserve 12 hours centrifugal then rejects and fall the supernatant, its precipitate is with the solid microsphere of lipid membrane embedding, promptly contain multienzyme complex Na-alginate microsphere, make D liquid;
Five, system contains the Na-alginate-polylysine microsphere of multienzyme complex, be E liquid: after placing 1.0% calcium chloride solution of 0.1% CHES to place 3-10 minute D liquid, be placed on again in the polylysine solution of 0.1%-0.5% 10-30 minute, formation is with the solid microsphere of lipid membrane embedding, promptly contain the Na-alginate polylysine microsphere of multienzyme complex, make E liquid;
Six, system contains the Na-alginate-polylysine-Na-alginate microsphere of multienzyme complex, be F liquid: the E liquid of making was put into 0.5-1.5% (W/V) Na-alginate solution 5-10 minute, formation is with the solid microsphere of lipid membrane embedding, promptly contain the Na-alginate-polylysine-Na-alginate microsphere of multienzyme complex, make F liquid;
Seven, system contains the Na-alginate-polylysine-Na-alginate microcapsule of multienzyme complex, be G liquid: F liquid is put into the 10-80MM citric acid receive liquid 5-10 minute, perhaps use EDTA liquid liquefaction Na-alginate-polylysine-Na-alginate microcapsule of 20-100MM, make microcapsule with lipid membrane embedding liquid, make G liquid, i.e. the liver metabolism proppant that declines;
Eight, finished product and preservation: with the G liquid of making, promptly the liver metabolism proppant that declines is placed in the enzyme stabilizers that contains albumin or serum albumin buffer agent and preserves.
Claims (2)
1, fulminant liver patient's liver metabolism proppant and preparation method thereof that declines that declines is characterized in that: the liver metabolism proppant prescription that declines is as follows: (100g is an example with preparation)
(1) glutathione peroxidase: 1.0g
(2) glutathione-S-transferase: 2.0g
(3) G-6-P deoxygenase: 1.0g
(4) glutathion (oxidized form): 5.0g
(5) glutathion (reduced form): 2.5g
(6) glutathion reductase: 1.0g
(7) G-6-P: 3.0g
(8) coenzyme II (oxidized form): 0.2g
(9) coenzyme II (reduced form): 2.0g
(10) UDP-glucuronyl transferase: 1.0g
(11) albumin (or serum albumin): 10.0g
(12) buffer agent: 71.3g
2, fulminant liver as claimed in claim 1 patient's liver metabolism proppant and preparation method thereof that declines that declines is characterized in that: the decline preparation method of metabolism proppant of liver is:
(1) manufacturing contains multienzyme complex Na-alginate mother solution, be A liquid: with glutathione peroxidase 1g, glutathione-S-transferase 2g, G-6-P deoxygenase 1g, glutathion (oxidized form) 5g, glutathion (reduced form) 2.5g, glutathion reductase 1g, G-6-P 3g, coenzyme II (oxidized form) 0.2g, coenzyme II (reduced form) 2g, UDP-glucuronyl transferase 1g etc. contains multienzyme complex and as protectant albumin (or serum albumin) 10g, buffer agent 71.3g makes and contains multienzyme complex Na-alginate mother solution (being A liquid), the basic mother solution of proceed step by step embedding after being made for;
(2), preparation lipid membrane, i.e. B liquid: phospholipid is dissolved in the chloroform, puts into the circular glass vessel, heated volatile forms lipid membrane.Getting A liquid side carries out aquation and forms how precious microcapsule and make B liquid in lipid membrane;
(3), preparation contains multienzyme complex liposome microsphere, be C liquid: get A liquid and be placed on and carry out aquation in the lipid membrane and form the multicell microcapsule, A liquid, B liquid side are gone in the ultrasonic device, carry out supersound process, or carry out sucking filtration repeatedly at the G4-G6 glass filter, form diameter 1-200 micron, make C liquid with the microcapsule of lipid membrane embedding liquid;
(4), system contains the Na-alginate microsphere of multienzyme complex, be D liquid: C liquid is put into contained 10% (W/V) L calcium chloride solution, under the 4C temperature, preserve 12 hours centrifugal then rejects and fall the supernatant, its precipitate is with the solid microsphere of lipid membrane embedding, promptly contain multienzyme complex Na-alginate microsphere, make D liquid;
(5), system contains the Na-alginate-polylysine microsphere of multienzyme complex, be E liquid: after placing 1.0% calcium chloride solution that contains 0.1%CHES to place 3-10 minute D liquid, be placed on again in the polylysine solution of 0.1%-0.5% 10-30 minute, formation is with the solid microsphere of lipid membrane embedding, promptly contain the Na-alginate polylysine microsphere of multienzyme complex, make E liquid;
(6), system contains the Na-alginate-polylysine-Na-alginate microsphere of multienzyme complex, be F liquid: the E liquid of making was put into 0.5-1.5% (W/V) Na-alginate solution 5-10 minute, formation is with the solid microsphere of lipid membrane embedding, promptly contain the Na-alginate-polylysine-Na-alginate microsphere of multienzyme complex, make F liquid;
(7), system contains the Na-alginate-polylysine-Na-alginate microcapsule of multienzyme complex, be G liquid: F liquid is put into the 10-80MM citric acid receive liquid 5-10 minute, perhaps use EDTA liquid liquefaction Na-alginate-polylysine-Na-alginate microcapsule of 20-100MM, make microcapsule with lipid membrane embedding liquid, make G liquid, i.e. the liver metabolism proppant that declines;
(8), finished product and preservation: with the G liquid of making, promptly the liver metabolism proppant that declines is placed in the enzyme stabilizers that contains albumin or serum albumin buffer agent and preserves.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN 99125265 CN1253832A (en) | 1999-12-02 | 1999-12-02 | Metabolism-supporting preparation for curing hepatic failure and its preparation method |
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| CN 99125265 CN1253832A (en) | 1999-12-02 | 1999-12-02 | Metabolism-supporting preparation for curing hepatic failure and its preparation method |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103167877A (en) * | 2010-08-02 | 2013-06-19 | 朱莉娅·卡塔里尼马斯泰利 | Composition comprising glutathione reductase and oxidized glutathione, and therapeutic uses thereof |
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1999
- 1999-12-02 CN CN 99125265 patent/CN1253832A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103167877A (en) * | 2010-08-02 | 2013-06-19 | 朱莉娅·卡塔里尼马斯泰利 | Composition comprising glutathione reductase and oxidized glutathione, and therapeutic uses thereof |
| US8852582B2 (en) | 2010-08-02 | 2014-10-07 | Giulia Cattarini Mastelli | Compositions comprising glutathione reductase and oxidized glutathione |
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