CN101984978A - Method for preparing compound coenzyme medicine - Google Patents
Method for preparing compound coenzyme medicine Download PDFInfo
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- CN101984978A CN101984978A CN201010503237.3A CN201010503237A CN101984978A CN 101984978 A CN101984978 A CN 101984978A CN 201010503237 A CN201010503237 A CN 201010503237A CN 101984978 A CN101984978 A CN 101984978A
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Abstract
The invention relates to a method for preparing compound coenzyme medicine and belongs to the technical field of medicine. The method comprises the steps of: adding pyrogen-free water in order to thaw fresh frozen yeast, smashing yeast cells by using physical method or mechanical method, refrigerating and centrifuging the smashed yeast cells, acquiring clear centrifuged solution, ultra-filtrating, and adjusting the content of the effective component in the ultra-filtrate, namely acquiring the compound coenzyme raw medicine, and adding in corresponding excipient or auxiliary material in order to make injected powder needle or oral-taken tablet or capsule. The invention not only increases the production efficiency but also lowers the production cost and ensures standard or over-standard content and quality of the effective component of the medicine.
Description
Technical field
The invention belongs to and do medical technical field, particularly a kind of new preparation method of Coenzyme Complex medicine.
Background technology
The Coenzyme Complex medicine is a kind of clinical medicine that is widely used in.2004, Aolute Biomedicines Research ﹠ Development Co., Ltd., Beijing, Beijing Su Liman biological medicine Science and Technology Ltd. and Hainan Kang Yong medicine company limited unite declared patent " a kind of preparation method of Coenzyme Complex medicine and Coenzyme Complex medicine thereof and clinical practice ", the patent No. is ZL200410058086X.This patent disclosure a kind of new Coenzyme Complex medicine preparation method and with the component of Coenzyme Complex from only containing coenzyme A, nadide, ATP and glutathion are brought up to for four kinds and are contained totally nine kinds of FMN, FAD, ADP, AMP, SAM etc. in addition.But the preparation method complexity that should invent, long processing time, cost height, unfavorable production in enormous quantities.
Summary of the invention
The objective of the invention is to overcome prior art preparation method complexity, long processing time, the cost height, the shortcoming of unfavorable production in enormous quantities proposes a kind of preparation method of new Coenzyme Complex, and this method is production technology tube list not only, time is short, cost is low, is beneficial to production in enormous quantities, and the product quality of product quality and the production of aforementioned patent method is suitable.
A kind of Coenzyme Complex medicament preparation that the present invention proposes is characterized in that this method may further comprise the steps:
1) fresh freezing yeast being added 0.5～5 times of apirogen water melts;
2) fresh yeast that melts physics method or Mechanical Method broken yeast cell;
3) with the yeast cells frozen centrifugation after the fragmentation, centrifuging temperature is 0 ℃～10 ℃, and centrifugal force is 10000-15000G, and centrifugation time is 30～60 minutes, must clarify centrifugal liquid;
4) centrifugal liquid is 5000～8000 dalton's ultrafiltration post ultrafiltration through the molecular weight that dams;
5) regulate the content of the contained active component of ultrafiltrate, make this ultrafiltrate reach this medicine content standard after, be the Coenzyme Complex crude drug;
6) in described Coenzyme Complex crude drug, add corresponding excipient, after the molecular weight that dams was 3000～5000 dalton's ultrafiltration post ultrafiltration and aseptic filtration, embedding also was lyophilized into the injection powder pin again; Or,, obtain dry powder with lyophilization or organic solvent precipitation method with described Coenzyme Complex crude drug, and add corresponding auxiliary material, make oral tablet or capsule.
Above-mentioned fresh freezing yeast can be young beer yeast, bakery yeast, the edible yeast that will produce freezing immediately (5 ℃～-20 ℃) and preserves, and storage life must not be above five days.
The physics method of above-mentioned broken yeast cell is meant freezes yeast liquid repeatedly deeply to-1 ℃～-5 ℃ and 1 ℃～5 ℃ (freeze-thaw method) of thawing, or speed is hot to 85 ℃～95 ℃, and speed is chilled to 5 ℃～10 ℃ (fast heat, fast cold process) again;
Described Mechanical Method is meant with the high pressure homogenization machine at pressure 50～150Mpa, 0 ℃～20 ℃ following broken yeast cells of temperature (high pressure homogenization), or grind broken yeast cell (polishing) with grinder.
Adopt the Coenzyme Complex medicine of above-mentioned preparation method, its coenzyme composition contains nine kinds of coenzyme A (C0A), nadide (NAD), glutathione, adenosine triphosphate (ATP), gland two phosphorus (ADP), adenosine phosphate (AMP), flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD) (FAD), ademetionines (SAM) etc.
The concentration of described coenzyme composition is as follows:
FAD 2～20μg/ml
FMN 2～20μg/ml
ATP 0.1～2.5mg/ml
ADP 0.1～0.5mg/ml
AMP 0.1～0.5mg/ml
SAM 1～20μg/ml
GSH 1～5mg/ml
CoA 100～300U/ml
NAD 0.1～0.5mg/ml
Characteristics of the present invention and effect:
Preparation method of the present invention has been removed activated carbon adsorption and desorbing, removes sub-displacement chromatography, has removed concentrating under reduced pressure and acetone precipitation, shortens and simplified technological process, has saved the time, has saved raw material, reduces cost, and is beneficial to mass industrialized production.And assurance meets or exceeds this medicine active component and content and quality standard.
Root a tree name yeast of the present invention is (edible, medicated beer, bread) for being small molecular weight material (molecular weight is all less than 1000 dalton) and yeast cells, the coenzyme of avirulent strains and organism contains micromolecule biological substance that abundant human body cell needs (as aminoacid, nucleotide, saccharide and lipoid substance) and inorganic ions, direct yeast cell with stored frozen, with physics (freeze thawing, speed heat speed is cold) or machinery (grinding, high pressure homogenization) method fragmentation, through high speed centrifugation, must clarify Cell sap, through dehydration and ultrafiltration, obtain to meet the crude drug of the corresponding active component of Coenzyme Complex medicine and content and quality standard again.
The specific embodiment
Coenzyme Complex medicament preparation embodiment 1, this method may further comprise the steps:
1) being used in freezing-5 ℃ of fresh freezing bakery yeasts of preserving one day down adds 0.5 times of apirogen water and melts;
2) with the high pressure homogenization machine at pressure 50Mpa, (at pressure 50～150Mpa, the scope that temperature is 0 ℃～20 ℃ all can) broken yeast cell under 10 ℃ of the temperature, also available grinder grinds broken yeast cell;
3) with the yeast cells frozen centrifugation after the fragmentation, centrifuging temperature is 5 ℃, and centrifugal force is 15000G, centrifugal 30 minutes, must clarify centrifugal liquid;
4) be 8000 daltonian ultrafiltration post ultrafiltration with the molecular weight that dams; ,
5) regulate the content of the contained active component of ultrafiltrate, make this ultrafiltrate reach this medicine content standard after, be the Coenzyme Complex crude drug;
6) in described Coenzyme Complex crude drug, add corresponding mannitol or human albumin excipient, after the molecular weight that dams (3000～5000 all can) daltonian ultrafilter ultrafiltration that is 5000 and aseptic filtration, embedding also is lyophilized into the injection powder pin again.
Measure the concentration of each coenzyme composition of present embodiment method preparation, the result is as follows:
FAD 5μg/ml
FMN 8μg/ml
ATP 2.0mg/ml
ADP 0.3mg/ml
AMP 0.15mg/ml
SAM 10μg/ml
GSH 1mg/ml
CoA 150U/ml
NAD 0.15mg/ml
Coenzyme Complex medicament preparation embodiment 2, this method may further comprise the steps:
1) being used in freezing-10 ℃ of fresh freezing beer yeasts of preserving two days down adds 5 times of apirogen water and melts;
2) fresh yeast that melts is heated to 85 ℃～95 ℃ rapidly, is cooled to 5 ℃～10 ℃ immediately, broken yeast cell;
3) with the yeast cells frozen centrifugation after the fragmentation, centrifuging temperature is 3 ℃, and centrifugal force is 10000G, centrifugal 60 minutes, must clarify centrifugal liquid;
4) be 6000 dalton's ultrafiltration post ultrafiltration with the molecular weight that dams;
5) regulate the content of the contained active component of ultrafiltrate, make this ultrafiltrate reach this medicine content standard after, be the Coenzyme Complex crude drug;
6) with described Coenzyme Complex crude drug, obtain dry powder, add corresponding auxiliary material (other adjuvant that can form or adopt this area to use always by carboxymethyl starch, lactose, magnesium stearate, binding agent, micropowder silica gel), make oral tablet with lyophilization.
Measure the concentration of each coenzyme composition of present embodiment method preparation, the result is as follows:
FAD 20μg/ml
FMN 18μg/ml
ATP 2.5mg/ml
ADP 0.2mg/ml
AMP 0.1mg/ml
SAM 15μg/ml
GSH 2mg/ml
CoA 150U/ml
NAD 0.1mg/ml
Coenzyme Complex medicament preparation embodiment 3, this method may further comprise the steps:
1) being used in freezing-20 ℃ of fresh freezing edible yeasts of preserving five days down adds 1 times of apirogen water and melts;
2) freeze to-1 ℃～-5 ℃ repeatedly deeply and melt 1 ℃～5 ℃, broken yeast cell;
3) with the yeast cells frozen centrifugation after the fragmentation, centrifuging temperature is 5 ℃, and centrifugal force is 12000G, centrifugal 60 minutes, must clarify centrifugal liquid;
4) be 5000 dalton's ultrafiltration post ultrafiltration with the molecular weight that dams;
5) regulate the content of the contained active component of ultrafiltrate, make this ultrafiltrate reach this medicine content standard after, be the Coenzyme Complex crude drug;
6) with described Coenzyme Complex crude drug, with the acetone or alcohol precipitation, obtain dry powder, add corresponding auxiliary material (can form by carboxymethyl starch, lactose, magnesium stearate, micropowder silica gel, or adopt this area other adjuvant commonly used), make capsule.
Measure the concentration of each coenzyme composition of present embodiment method preparation, the result is as follows:
FAD 1μg/ml
FMN 1.5μg/ml
ATP 1.5mg/ml
ADP 0.1mg/ml
AMP 0.2mg/ml
SAM 12μg/ml
GSH 2.5mg/ml
CoA 130U/ml
NAD 0.5mg/ml
Claims (3)
1. a Coenzyme Complex medicament preparation is characterized in that, this method may further comprise the steps:
1) fresh freezing yeast being added 0.5～5 times of apirogen water melts;
2) fresh yeast that melts physics method or Mechanical Method broken yeast cell;
3) with the yeast cells frozen centrifugation after the fragmentation, centrifuging temperature is 0 ℃～10 ℃, and centrifugal force is 10000-15000G, and centrifugation time is 30～60 minutes, must clarify centrifugal liquid;
4) centrifugal liquid is 5000～8000 dalton's ultrafiltration post ultrafiltration through the molecular weight that dams;
5) regulate the content of the contained active component of ultrafiltrate, make this ultrafiltrate reach this medicine content standard after, be the Coenzyme Complex crude drug;
6) in described Coenzyme Complex crude drug, add corresponding excipient, after the molecular weight that dams was 3000～5000 dalton's ultrafiltration post ultrafiltration and aseptic filtration, embedding also was lyophilized into the injection powder pin again; Or,, obtain dry powder with lyophilization or organic solvent precipitation method with described Coenzyme Complex crude drug, and add corresponding auxiliary material, make oral tablet or capsule.
2. preparation method as claimed in claim 1 is characterized in that, described fresh freezing yeast is for preserving young beer yeast, bakery yeast, the edible yeast produced freezing immediately (5 ℃～-20 ℃), and storage life must not be above five days.
3. preparation method as claimed in claim 1 is characterized in that, the physics method of described broken yeast cell is meant freezes yeast liquid to-1 ℃～-5 ℃ repeatedly deeply and melt 1 ℃～5 ℃, or speed heat to 85 ℃～95 ℃ speed are chilled to 5 ℃～10 ℃; Described Mechanical Method is meant with the high pressure homogenization machine at pressure 50～150Mpa, 0 ℃～20 ℃ following broken yeast cells of temperature, or grind broken yeast cell with grinder.
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| CN2010105032373A CN101984978B (en) | 2010-09-30 | 2010-09-30 | Method for preparing compound coenzyme medicine |
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| CN2010105032373A CN101984978B (en) | 2010-09-30 | 2010-09-30 | Method for preparing compound coenzyme medicine |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104623626A (en) * | 2013-07-17 | 2015-05-20 | 北京双鹭药业股份有限公司 | Stable compound coenzyme preparation as well as preparation method and applications thereof |
| CN105481923A (en) * | 2015-12-30 | 2016-04-13 | 平光制药股份有限公司 | Preparation method of nicotinamide adenine dinucleotide |
| CN106755210A (en) * | 2016-12-12 | 2017-05-31 | 安徽翠鸟生物技术有限公司 | Coenzyme mixed solution and preparation method thereof |
| CN109651470A (en) * | 2019-01-24 | 2019-04-19 | 开封康诺药业有限公司 | A kind of separation method of Coenzyme I and other macromolecular substances |
| WO2022082487A1 (en) * | 2020-10-21 | 2022-04-28 | 朱上翔 | Anti-aging composite nutrient containing coenzymes and bioactive hydrogen, preparation method therefor and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1586502A (en) * | 2004-08-13 | 2005-03-02 | 北京奥路特生物医药研发有限公司 | Process for preparing compound coemzyme medicine and its compound coemzyme medicine and clinical use |
-
2010
- 2010-09-30 CN CN2010105032373A patent/CN101984978B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1586502A (en) * | 2004-08-13 | 2005-03-02 | 北京奥路特生物医药研发有限公司 | Process for preparing compound coemzyme medicine and its compound coemzyme medicine and clinical use |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104623626A (en) * | 2013-07-17 | 2015-05-20 | 北京双鹭药业股份有限公司 | Stable compound coenzyme preparation as well as preparation method and applications thereof |
| CN105481923A (en) * | 2015-12-30 | 2016-04-13 | 平光制药股份有限公司 | Preparation method of nicotinamide adenine dinucleotide |
| CN105481923B (en) * | 2015-12-30 | 2018-07-31 | 平光制药股份有限公司 | A kind of preparation method of nicotinamide adenine dinucleotide |
| CN106755210A (en) * | 2016-12-12 | 2017-05-31 | 安徽翠鸟生物技术有限公司 | Coenzyme mixed solution and preparation method thereof |
| CN109651470A (en) * | 2019-01-24 | 2019-04-19 | 开封康诺药业有限公司 | A kind of separation method of Coenzyme I and other macromolecular substances |
| WO2022082487A1 (en) * | 2020-10-21 | 2022-04-28 | 朱上翔 | Anti-aging composite nutrient containing coenzymes and bioactive hydrogen, preparation method therefor and application thereof |
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| CN101984978B (en) | 2012-06-27 |
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Application publication date: 20110316 Assignee: Beijing SL Lisheng Medical Technology Co.,Ltd. Assignor: HAINAN KANGYONG PHARMACEUTICALS Co.,Ltd.|SUQIANBOHUA BIOTECHNOLOGY Co.,Ltd. Contract record no.: 2013990000760 Denomination of invention: Process for preparing compound coemzyme medicine and its compound coemzyme medicine and clinical use Granted publication date: 20120627 License type: Exclusive License Record date: 20131113 |
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Owner name: SHANGHAI CHANGXUE BIOTECHNOLOGY RESEARCH AND DEVEL Free format text: FORMER OWNER: SUQIANBOHUA BIOTECHNOLOGY CO., LTD. Effective date: 20140509 |
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Effective date of registration: 20140509 Address after: Building No. 53 Guangyuan Haidian Hainan city of Haikou province people's road 570208 building 503 room 5 Patentee after: HAINAN KANGYONG PHARMACEUTICALS Co.,Ltd. Patentee after: Shanghai Chang Xue biotechnology research and Development Center Address before: Building No. 53 Guangyuan Haidian Hainan city of Haikou province people's road 570208 building 503 room 5 Patentee before: HAINAN KANGYONG PHARMACEUTICALS Co.,Ltd. Patentee before: SUQIANBOHUA BIOTECHNOLOGY Co.,Ltd. |
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