CN100430402C - Method of refining plamatine from herba fibranreae recisae total ulkuloid and its application - Google Patents
Method of refining plamatine from herba fibranreae recisae total ulkuloid and its application Download PDFInfo
- Publication number
- CN100430402C CN100430402C CNB2004100139881A CN200410013988A CN100430402C CN 100430402 C CN100430402 C CN 100430402C CN B2004100139881 A CNB2004100139881 A CN B2004100139881A CN 200410013988 A CN200410013988 A CN 200410013988A CN 100430402 C CN100430402 C CN 100430402C
- Authority
- CN
- China
- Prior art keywords
- acid
- palmatine
- hours
- refining
- dry
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention relates to a method for refining palmatine from fibraurea stem total alkaloid. The present invention uses the method of using the solvent pH separation or the column chromatography separation of fibraurea stem total alkaloid of which the palmatine content is not higher than 96%, wherein the fibraurea stem total alkaloid is prepared by the prior art. The dissolving performance difference of different alkaloids is used, and the alkaloids are separated by using the principle of pH difference or solvent polarity difference. The refining operation is carried out by the assistance of relevant technology. The palmatine yield rates respectively are 40% to 60% and 20% to 40%. The palmatine content is about 99.05 or is higher than 99.0% by a high-efficiency liquid-phase measuring method which is HPLC measurement. The present invention solves the defect that the palmatine content can not be increased to be higher than 96.0% in the prior art even by repeated preparation, increases purity, and improves medical safety. The present invention can be made into a plurality of kinds of formulations, and has the advantages of simple method, practicality and good effect.
Description
Technical field
The present invention relates to a kind of method of refining palmatine, particularly a kind of method of from the herba fibraureae recisae total alkaloids, making with extra care palmatine.
Background technology
Palmatine has another name called palmatine, palmatine, Palmatine, and English name is Palmatine then, has 5,6-dihydro-2,3,9,10-tetramethoxy dibenzo (a, g) quinolizine structure.This is a kind of alkaloid that extensively is present in the berberis.
Pharmacological research confirms that palmatine has broad-spectrum antibacterial action, to bacterium such as gram-positive microorganism, Gram-negative bacteria, and common morbific 12 kinds of moulds and comprise that the multiple virus of common cold virus is all inhibited.And palmatine can strengthen leukocytic phagocytic activity in the body.Clinically, can be applied to treat the leukopenia that upper respiratory tract infection, tonsillitis, enteritis, dysentery, genito-urinary system infection, surgery and gynecological infection inflammation, chemotherapy and radiotherapy cause, and infectious hepatitis, cute conjunctivitis etc.
Modern animal pharmacology experiment confirm, palmatine also has antiarrhythmic effect, can strengthen myocardial contraction, and the myocardial infarction of animal is had provide protection, can reduce myocardial infarction area.
At present, common resulting palmatine is that form with its corresponding salt exists example hydrochloric acid palmatine, sulfuric acid palmatine etc.
Main chemical in the plant herba fibraureae recisae (another name coptis rattan, Northern Dutchmanspipe Vine, Fibraurea tinctoria lour) is an alkaloid, and wherein the content of palmatine is up to 3%.Therefore, it is commonly used and practical extracting palmatine from the plant herba fibraureae recisae.This extraction palmatine method or technology be used widely.Chief editors such as Yang Yun " Chemistry for Chinese Traditional Medicine composition extraction separation handbook has from the herba fibraureae recisae plant method or the technology of extracting palmatine.
The method of this extraction palmatine or the key step of technology be with the herba fibraureae recisae meal with acetic acid flood the sour water steeping fluid, add sodium-chlor, regulate pH value to 8～9, filtration, drying are used alcohol reflux, re-adjustment pH value to 2, precipitation is separated out, filter, get the hydrochloride of herba fibraureae recisae total alkaloids, be amorphous yellow powder shape thing.It is adopted acid base titration or gravimetric determination content, and palmatine is about 92.0%.As re-refining by above-mentioned technology, what obtain is yellow powder shape thing still, measures its content and is about 98.5%, is about 96% but measure palmatine content with high performance liquid phase assay method (HPLC method).The content of main related impurities jateorhizine wherein is about 3.0%, and Berberine is about 1.0%.Carry out the refining repeatedly of above-mentioned technology again, the content and the ratio of its impurity jateorhizine and Berberine remain unchanged substantially.
The First Principles of medication is a safety clinically.The objective indicator of drug safety is the purity of main ingredient composition.In theory, it is better pure to heal, and considers practical feasibility and economy, in the world Tong Hang requirement be drug content should reach 99.0% or more than, foreign matter content 1.0% or below.And the technology of above-mentioned prior art or method produce that the content of palmatine is the highest can only to be reached about 96.0%, and impurity jateorhizine content but has about 3.0%, and Berberine also has about 1.0%.Therefore, the purity of its palmatine does not meet the requirement of modern pharmacology, can not satisfy modern pharmaceutical industry to the bulk drug requirement of high purity.
Why prior art can't solve the palmatine purity problem, is because do not find suitable process conditions, so can't break through this technical barrier.
Summary of the invention
Purpose of the present invention just is to overcome above-mentioned defective, studies a kind of palmatine content that improves and reaches 99% and above process for purification or technology.
Technical scheme of the present invention: the method for refining palmatine from the herba fibraureae recisae total alkaloids, get the herba fibraureae recisae total alkaloids, its major technique is characterised in that and adopts solvent pH to separate:
(1) the herba fibraureae recisae total alkaloids is 1 part, adds 5～50 parts of deionized waters, heating for dissolving;
(2) regulate pH value 10～14 with alkali lye, insulation;
(3) add 0.5～2.0 part in refining sodium-chlor, stir, place;
(4) separate out precipitation fully, filter, remove the saliferous mother liquor;
(5) with alkaline water thorough washing, the precipitation of pH value 10～14, drain filter cake;
(6) dry under 60～80 ℃ of temperature;
(7) dry thing is suspended in 20～100% the ethanol, insolubles is removed in reflux, dissolving;
(8) regulate between the pH value 1～6.5 with acidic aqueous solution again, obtain palmatine salt; Acidic aqueous solution is hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid or organic acid acetate, propionic acid, butyric acid, methylsulfonic acid, Citric Acid, tartrate, liquor epinephrinae bitartratis ophthalmicus, fumaric acid, lactic acid, phenylformic acid, Whitfield's ointment, toxilic acid, Sorbic Acid, L-glutamic acid, the xitix of mineral acid;
(9) place under 2～10 ℃ of low temperature, crystallization is separated out, and filters, and removes mother liquor;
(10) with the pure liquid wash crystallization several of sour same concentrations of the same race, drain;
(11) under 50～90 ℃ of temperature dry 12 hours, can get the palmatine salt of purifying, recovery rate is 40～60%.
Advantage of the present invention is to utilize the difference of different alkaloids on solubility property with effect, select for use pH value difference or solvent polarity difference that it is separated, thereby broken through the difficult problem that prior art can't further improve palmatine content, improved palmatine content reach more than 99.0% and (press high performance liquid phase assay method (HPLC method), reduced the content of impurity, alleviated impurity and almost can ignore, also improved the result of treatment of palmatine medicine simultaneously the harm even this harm of human body; Solvent pH value partition method of the present invention or column chromatography for separation method are opened up and have been enriched and carry out purified field and means from the herba fibraureae recisae total alkaloids, realize the raising of palmatine content with low-cost simple and feasible again technological method.
The effect of purified palmatine of the present invention and advantage are that process is simple, process short, and cost is low, finished product yield height, and curative effect is good.
Embodiment
Embodiment 1:
Adopt solvent pH value partition method:
Herba fibraureae recisae total alkaloids 100g, this herba fibraureae recisae total alkaloids are the products that adopts above-mentioned prior art processes to extract, and add deionized water 1000ml, and heating makes it dissolving; The pH value to 14 of the NaOH solution regulator solution with 10% is incubated 2 hours; Add refining sodium-chlor (being meant pharmaceutical grade) 77g, stir, placed 12 hours, precipitation is separated out fully; Filter, remove the saliferous mother liquor; With the pH value is 14 alkalization water thorough washing, precipitation, drains, filter cake; Be placed under 70 ℃ of temperature dry more than 12 hours then; Dry thing is suspended in reflux in 95% the ethanol, and palmatine fully is dissolved in the pure liquid; Filter, remove insoluble substance; Filtrate is regulated pH value to 3.5 with 10%HCl liquid; And then it is following more than 24 hours to place it in 2～10 ℃ of low temperature; At this moment, there are a large amount of yellow needle crystals to separate out; Filter, remove mother liquor, crystallization is 3.5 95% ethanolic soln thorough washing with the pH value; Drain, dry more than 12 hours under 80 ℃ of temperature, promptly obtain the hydrochloride of palmatine.
Measure with high-efficient liquid phase technique, the content of palmatine wherein is equal to or greater than 99.0%, and the content of impurity jateorhizine is less than 1.0%, and the impurity Berberine does not almost detect, and two impurity sums are less than 1%; The recovery rate of palmatine is between 40～80%.
If the purity of raw material herba fibraureae recisae total alkaloids does not reach requirement, then can re-refine as stated above 1,2 time.
Be the application of purified palmatine of the present invention below.
Embodiment 3: the preparation of palmatine hydrochloride injection liquid
Get palmatine hydrochloride 20g, add water for injection, stir and make it and dissolve, add water for injection again to 800ml, measure the pH value, regulate the pH value 3.0～8.0 with 10% hydrochloric acid or 10% sodium hydroxide solution, occurrence is 5.5; Add about 0.2% needle-use activated carbon, stir; Insulation was placed 30 minutes, and clarification filtration adds the injection water to 1000ml with filtrate; Sterile Filtration is sub-packed in the ampoule of 1ml specification, and sterilization promptly got the palmatine hydrochloride injection formulation in 30 minutes under 100 ℃ of temperature.
Embodiment 4: the preparation of palmatine hydrochloride powder injection
Get palmatine hydrochloride 20g, increase progressively hybrid system by equivalent and add N.F,USP MANNITOL 2000g gradually, mix, aseptic subpackaged in cillin bottle, seal, make powder injection.
Embodiment 5: the preparation of palmatine hydrochloride lyophilized injection
Get palmatine hydrochloride 20g, add water for injection to about 800ml, survey the pH value, and adjust between the pH value 3.0～8.0 with 0.1M hydrochloric acid or sodium hydroxide solution, scope specifically gets 5.5 4.5～6.5 preferably; Add the N.F,USP MANNITOL of 20g and 0.2% needle-use activated carbon, stir and make its dissolving, mixing, be incubated 30 minutes, temperature is ℃ clarification filtration; Add water for injection again to 1000ml, Sterile Filtration is sub-packed in the 10ml cillin bottle; Send in the loft drier of the freezing in advance freeze drier to-45 ℃ pre-freeze 2 hours; Vacuumize subsequently and reach 0.013KP
aTo the shelf heating, make it heat up per hour 2～4 ℃; To rise in 0 ℃, goods moisture entrapment about 5% the time when shelf temperature, can be rapidly heated, and per hour rises 4～10 ℃; Consistent with shelf temperature and in the time of 35～40 ℃ when products temperature, be incubated 4～6 hours, finish heating, outlet makes freeze-drying pin preparation.
Embodiment 6: the preparation of palmatine hydrochloride sodium chloride injection
Get palmatine hydrochloride 20g, add water for injection, stir or under heating (25～100 ℃) condition, stir and make its dissolving; Add water for injection again to about 80000ml, survey the pH value, and adjust between the pH value 3.0～8.0 with 10% hydrochloric acid or sodium hydroxide solution, scope specifically gets 5.5 4.5～6.5 preferably; Add sodium chloride for injection 900g, stir and make its dissolving, the mosm concentration that makes solution is between 280～320mOsm/L; The needle-use activated carbon of adding 0.2%, stirring makes and mixes; Under 80 ℃ of temperature, be incubated 30 minutes, clarification filtration; Filtrate adds the injection water to 100000ml, and Sterile Filtration is sub-packed in the vial of 100ml, jumps a queue, and rolls aluminium lid; Hot pressing (121 ℃) sterilization 30 minutes promptly gets palmatine hydrochloride chloride injection liquid formulation.
Embodiment 7: the preparation of palmatine hydrochloride glucose injection
Get palmatine hydrochloride 20g, add water for injection, stir and make its dissolving; Add water for injection again to about 80000ml, survey the pH value, and adjust the pH value between 3.0～8.0 with 10% hydrochloric acid or sodium hydroxide solution, scope specifically gets 5.5 4.5～6.5 preferably; Add glucose for injection 5000g, stir and make its dissolving; The needle-use activated carbon of adding 0.2%, stirring makes and mixes; Under 80 ℃ of temperature, be incubated 30 minutes, clarification filtration; Filtrate adds the injection water, is supplemented to 100000ml; Sterile Filtration is sub-packed in the vial of 100ml, jumps a queue, and rolls aluminium lid; Hot pressing (121 ℃) sterilization 30 minutes promptly gets the palmatine hydrochloride glucose injection formulation.
Embodiment 8:
Get palmatine hydrochloride 100g
Microcrystalline Cellulose 25g
Pregelatinized Starch 25g
Polyvinylpolypyrrolidone K30 is an amount of
Micropowder silica gel 1g
Magnesium Stearate 2g
The salt of palmatine hydrochloride is crossed 60 mesh sieves get fine powder, get 1 part, add 1.5 parts of weighting agent Microcrystalline Celluloses, 0.6 part of disintegrating agent pregelatinized Starch mixes, and the adding tackiness agent is 6% polyvinylpolypyrrolidone K
30Solution is made softwood, and cross 18 mesh sieves and make particle, 80 ℃ of dryings, the whole grain of 18 mesh sieves adds the lubricant of 0.5% Magnesium Stearate, mixes, and compressing tablet becomes 1000 or fill 1000 capsules, promptly gets palmatine tablet or capsule.
Claims (2)
1. the method for refining palmatine from the herba fibraureae recisae total alkaloids is got the herba fibraureae recisae total alkaloids, it is characterized in that adopting solvent pH to separate:
(1) the herba fibraureae recisae total alkaloids is 1 part, adds 5～50 parts of deionized waters, heating for dissolving;
(2) regulate pH value 10～14 with alkali lye, insulation;
(3) add 0.5～2.0 part in refining sodium-chlor, stir, place;
(4) separate out precipitation fully, filter, remove the saliferous mother liquor;
(5) with alkaline water thorough washing, the precipitation of pH value 10～14, drain filter cake;
(6) dry under 60～80 ℃ of temperature;
(7) dry thing is suspended in 20～100% the ethanol, insolubles is removed in reflux, dissolving;
(8) regulate between the pH value 1～6.5 with acidic aqueous solution again, obtain palmatine salt; Acidic aqueous solution is hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid or organic acid acetate, propionic acid, butyric acid, methylsulfonic acid, Citric Acid, tartrate, liquor epinephrinae bitartratis ophthalmicus, fumaric acid, lactic acid, phenylformic acid, Whitfield's ointment, toxilic acid, Sorbic Acid, L-glutamic acid, the xitix of mineral acid;
(9) place under 2～10 ℃ of low temperature, crystallization is separated out, and filters, and removes mother liquor;
(10) with the pure liquid wash crystallization several of sour same concentrations of the same race, drain;
(11) under 50～90 ℃ of temperature dry 12 hours, can get the palmatine salt of purifying, recovery rate is 40～60%.
2. method of from the herba fibraureae recisae total alkaloids, making with extra care palmatine according to claim 1, it is characterized in that adopting solvent pH separation steps (2) insulation more than 2 hours, step (3) stirs, places more than 2 hours, step (6) is dry more than 12 hours, step (9) low temperature was placed more than 24 hours, and step (11) is dry more than 12 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100139881A CN100430402C (en) | 2004-02-02 | 2004-02-02 | Method of refining plamatine from herba fibranreae recisae total ulkuloid and its application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100139881A CN100430402C (en) | 2004-02-02 | 2004-02-02 | Method of refining plamatine from herba fibranreae recisae total ulkuloid and its application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1651432A CN1651432A (en) | 2005-08-10 |
| CN100430402C true CN100430402C (en) | 2008-11-05 |
Family
ID=34867855
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004100139881A Expired - Fee Related CN100430402C (en) | 2004-02-02 | 2004-02-02 | Method of refining plamatine from herba fibranreae recisae total ulkuloid and its application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100430402C (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101596194B (en) * | 2009-07-14 | 2012-01-11 | 中国科学院武汉病毒研究所 | Application of palmatine in medicine for treating West Nile virus infection |
| CN101596192B (en) * | 2009-07-14 | 2011-08-17 | 中国科学院武汉病毒研究所 | Application of palmatine in medicine for treating dengue virus infection |
| CN101596193B (en) * | 2009-07-14 | 2011-05-11 | 中国科学院武汉病毒研究所 | Application of palmatine in medicine for treating yellow fever virus infection |
| CN102408424A (en) * | 2011-09-28 | 2012-04-11 | 长春工业大学 | Method for preparing Palmatine by utilizing hybrid coptis total alkaloid with isoquinoline structure |
| CN108014517A (en) * | 2017-12-20 | 2018-05-11 | 泰州医药城国科化物生物医药科技有限公司 | A kind of method using polysaccharide-based medium to Protoberberine Alkoloids enriching and purifying |
| CN110105353A (en) * | 2019-06-18 | 2019-08-09 | 云南润嘉药业有限公司 | Fibrauretine crystalline form and the preparation method and application thereof |
| JP2023519008A (en) * | 2020-03-27 | 2023-05-09 | 深▲セン▼市水梹榔生物科技有限公司 | Arecoline salt and its preparation method and product |
-
2004
- 2004-02-02 CN CNB2004100139881A patent/CN100430402C/en not_active Expired - Fee Related
Non-Patent Citations (4)
| Title |
|---|
| pH值对黄藤中巴马汀盐析的影响. 李晓莹，廖华卫.广东药学院学报，第15卷第3期. 1999 |
| pH值对黄藤中巴马汀盐析的影响. 李晓莹，廖华卫.广东药学院学报，第15卷第3期. 1999 * |
| 巴马汀提取工艺的改进. 罗连贵.中国医药工业杂志，第21卷第4期. 1990 |
| 巴马汀提取工艺的改进. 罗连贵.中国医药工业杂志，第21卷第4期. 1990 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1651432A (en) | 2005-08-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102286098B (en) | Production method of natural hirudin | |
| CN111732622B (en) | Method for extracting hesperidin from immature bitter orange | |
| CN100430402C (en) | Method of refining plamatine from herba fibranreae recisae total ulkuloid and its application | |
| CA3157550C (en) | Injectable psychoactive alkaloid composition and preparation thereof | |
| EP3023416A1 (en) | Preparation of (-)-huperzine a | |
| CN101747307A (en) | Glycyrrhizic acid removal glycyrrhiza flavonoid and medicament composition thereof | |
| JP2004323420A (en) | NEW SUBSTANCE HAVING alpha-GLUCOSIDASE INHIBITORY ACTIVITY AND FOOD CONTAINING THE SAME | |
| CN102285970B (en) | Esomeprazole compound, preparation method and pharmaceutical compoistion | |
| CN101597271A (en) | The derivative of Ailamode, its preparation method and medicinal application | |
| JP2012513957A5 (en) | ||
| CN101564405A (en) | Application of total aglycone of himalayan teasel roots and single-component hederagenin in medicaments preparing Alpha-glucosidase inhibitor | |
| CN110627792A (en) | Pentoxifylline compound | |
| CN100372544C (en) | Silkworm sand total alkaloid and preparation thereof | |
| CN113429452B (en) | Acylated mogroside derivatives as anti-inflammatory agents and anti-inflammatory compositions | |
| CN102532166A (en) | Preparation method of refined ceftezole acid | |
| CN103709219A (en) | Tylosin extraction method | |
| CN107880054A (en) | A kind of method for preparing high-purity tetraodotoxin | |
| CN110144015B (en) | Method for synchronously extracting and purifying ganoderan, ganoderma triterpenic acid and amino acid | |
| CN103446046A (en) | High-purity tropisetron citrate injection | |
| CN112353799A (en) | Cimetidine composition for injection and preparation method and application thereof | |
| CN101301304A (en) | Chinese medicinal composition for treating ischemic stroke and preparation thereof | |
| CN101343330A (en) | Preparation method for panax ginseng polyoses extract | |
| WO2019156307A1 (en) | Method for preparing rhus verniciflua stokes extract powder containing high concentration of nano-sized fisetin having enhanced water-solubility, and anti-cancer composition containing same | |
| CN113995798B (en) | Preparation method of lycium ruthenicum anthocyanin extract and freeze-dried powder and application of lycium ruthenicum anthocyanin extract and freeze-dried powder in products for resisting gouty arthritis and reducing uric acid | |
| EP3044203B1 (en) | Process for the production of high-density mesalamine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20081105 Termination date: 20210202 |