CN1240706C - Process for producing super critical extracting caterpillar fungus deoxynucleoside - Google Patents
Process for producing super critical extracting caterpillar fungus deoxynucleoside Download PDFInfo
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- CN1240706C CN1240706C CNB011269103A CN01126910A CN1240706C CN 1240706 C CN1240706 C CN 1240706C CN B011269103 A CNB011269103 A CN B011269103A CN 01126910 A CN01126910 A CN 01126910A CN 1240706 C CN1240706 C CN 1240706C
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/062—Ascomycota
- A61K36/066—Clavicipitaceae
- A61K36/068—Cordyceps
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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Abstract
The present invention relates to a production method of supercritically extracted caterpillar fungus deoxynucleoside, which belongs to the field of the deep processing of edible fungi and medicinal fungi. The present invention overcomes the disadvantages of great energy consumption, long time and complicatedness of the traditional technologies, such as water boiling, alcohol extraction, concentration, etc. The present invention has the advantages of rapid obtainment of a natural active ingredient, no environmental pollution and comprehensive raw material utilization. The present invention becoming an important technology for the deep processing of the edible fungi and the medicinal fungi reaches the international leading level. The present invention is characterized in that ethanol is adopted as an entrainer, and a 3'-deoxyadenosine predominated active ingredient with the purity of 50 to 99.9%, which is obtained under alternative conditions, is a raw material for health foods, cosmetics or medicines. The product performing the action of oxidation resistance, virus resistance, tumor resistance and organism immunity regulation is also an important reagent in the field of gene engineering, the product is also possibly relevant to renal failure, and therefore, the present invention capable of creating great economic benefits has great development values.
Description
Technical field
The invention belongs to the deep processing field of edible medicinal fungi.
Background technology
Cordyceps sinensis fungus is precious edible medicinal fungi mostly, and the artificial culture development of technology makes rare wild fungus that the value of economic development arranged in recent years.Type species one Cordyceps militaris (L.) Link. in the Cordyceps can carry out large scale cultivating, and the effective constituent of its artificial finished product and pharmacological property can match in excellence or beauty with natural product, also has and invigorates the lung and the kidney, relieving cough and reducing sputum effect.So the many artificial culture products in the Cordyceps have precious edible pharmaceutical use.Number of patent application 92101051.6 has been introduced their prospect and value.Wherein pluck the substratum behind the stroma, generally all go out of use, therefore, as the raw material extracting effective components, turning waste into wealth has significant values.
When the traditional Chinese medicine extraction process, take poach, alcohol extracting, boiling concentration technique more, energy consumption is big, operates loaded down with trivial detailsly, also has many refuses to cause environmental pollution.So adopting state-of-the-art technology to extract active skull cap components has huge economic and social value.And supercritical carbon dioxide extraction method just possesses the low temperature inert environments, does not influence the effective constituent activity, and is nontoxic nonflammable, safe in utilization, do not pollute the environment no solvent residue, heavy metal free ion.Therefore, adopt supercritical technology to extract activeconstituents in the Chinese caterpillar fungus culture, create a kind of novel process, novel method has practical value.
Summary of the invention
The objective of the invention is to create a kind of artificial culture thing with Cordyceps bacterial strains such as Chinese caterpillar fungus, pupa grass, Cordyceps hawkesii Gary, Paecilomyces variotis is raw material, extract the method for deoxynucleoside active component, thereby obtain deoxynucleoside monomer or component, make monomer meet the former medicine requirements of customs declaration of a kind new medicine, make component meet two kind new medicine requirements of customs declaration.
Technical scheme of the present invention is as follows.
A kind of production method of super critical extracting caterpillar fungus oxygen nucleosides, be to be raw material with the fermented product after edible medicinal fungi Chinese caterpillar fungus or the Cordyceps militaris (L.) Link. artificial culture, adopt supercritical technology extraction deoxynucleoside effective constituents, and obtain cordycepin as the entrainment agent decompression separation with ethanol, pass through traditional technology and then produce corresponding capsule, the product of different dosage forms such as injection; The solid material granularity is the 20-60 order, and its content of cordycepin is at 0.8mg/g--18mg/g; Adopt supercritical technology extraction deoxidation glycoside effective constituent, its extraction kettle pressure 15-50Mpa; Separating still pressure is 5-25Mpa, and the pressure of separating still is all the time less than the pressure of extraction kettle in the same flow process.
Adopting the solid or semisolid of Chinese caterpillar fungus or Cordyceps militaris (L.) Link. artificial culture secondary fermentation thing is raw material, comprises the surplus stock behind the super critical extracting caterpillar fungus oil, and its water content is at 1-60%, the employing solid material, and water content is 6-10%.
Make entrainment agent with ethanol, alcohol concn is made entrainment agent at 5-99% until the dehydrated alcohol that adopts city's dress.
The present invention separates and obtains the close several deoxynucleosides of composition, 3 '-deoxynucleoside, 3 '-amino-3 '-Desoxyadenosine, become the polycomponent thing, main component cordycepin 3 '-ratio of deoxynucleoside is between 30-99.9%.
Adopt the deoxynucleoside class powder raw material of supercritical technology preparation, be processed into tablet or capsule, every contain 3 '-deoxynucleoside 5-200mg between.
Deoxynucleoside class powder raw material with the supercritical technology preparation is processed into lyophilized injection, and every contains deoxynucleoside powder content is 12.5-200mg.
Narrate technical process of the present invention below:
The caterpillar fungus deoxynucleoside effective constituents that the present invention makes, it is characterized in that: adopt the solid after Chinese caterpillar fungus or the Cordyceps militaris (L.) Link. artificial culture or semi-solidly be raw material, (comprise super critical extracting caterpillar fungus oil after surplus stock), its water content is at 1-60%, the best solid material that adopts, water content is 6-10%.Raw material of the present invention is meant the bacterium slag of bacterial strain behind product after the artificial culture or harvesting stroma in Chinese caterpillar fungus and the Cordyceps.The bacterial strain bacterial classification is not limited in the right of the present invention, mainly be meant the solid or the semisolid raw material that contain cordycepin, as: the substratum of solid fermentation, the dry bacterium powder behind the maize gruel substratum of semisolid fermentation and the liquid fermenting.These products are easy to preserve transportation when water content 6-10%.For example: Chinese caterpillar fungus fermentation bacterium powder, Cordyceps militaris (L.) Link. fungus powder, pupa grass rice medium, Paecilomyces varioti zymophyte powder etc.After adopting above-mentioned raw materials, do not influence the extraction of deoxynucleoside thing with supercritical technology extraction oily matter.What particularly point out is that through the surplus stock behind the extracting caterpillar fungus oil, its water content is about 1-5%, and is also more much lower than commercially available usually rice water content, do not influence the extraction of deoxynucleoside.
The present invention produces the method for deoxynucleoside, it is characterized in that: the granularity of solid material between the 20-60 order, its content of cordycepin 〉=0.5mg/g, best more than 0.8mg/g.As everyone knows, have 350 kinds more than in the Cordyceps, for example: Chinese caterpillar fungus＜Codyceps SinerIsis 〉, Cordyceps militaris (L.) Link.＜Codyceps militaris, Cordyceps hawkesii Gary＜Coz-dycePS Hawkesii, pupa draws up mould (PaecitweeSMUtarae) etc.These bacterial strains are seeded in through artificial culture can both be successful on the substratum more than 50 kinds such as rice medium corn, jowar, wheat, millet, silkworm chrysalis, cocoon chrysalis, bat bat moth larvae, egg white,
The difficult son peace body that forms of Chinese caterpillar fungus, Cordyceps militaris (L.) Link. more easily forms sporophore.Divide them into two classes like this: one is sporophore so long: two are fermented product＜substratum, zymophyte powder 〉.The former can directly become commodity, list marketing; The latter, as Chinese caterpillar fungus fermentation bacterium powder, Cordyceps militaris (L.) Link. fungus powder etc. can be made protective foods or medicine, pupa grass rice medium＜bacterium base, bacterium slag that wherein turnout is bigger 〉, do not utilize mostly.So the bacterium slag that the asexual zymophyte powder of above-mentioned bacterial strains and artificial sexual growth are plucked behind the stroma becomes main raw material of the present invention, defines to contain cordycepin.
In the technical application process, the bacterium culture will be pulverized the back and add in the extraction kettle, is advisable with the 20-60 order, too carefully easily stop up, too slightly the extraction time long easily residual, yield is low.
Technical characterictic of the present invention is the Chinese caterpillar fungus of adopting and the artificial culture thing of Chinese caterpillar fungus class, and its cordycepin content 〉=0.5mg/g is best more than 0.8mg/g, below the 18mg/g.Because cordycepin (3 '-Desoxyadenosine) be the main component of deoxynucleoside class, be its labeled component, activeconstituents.Natural cs and pupa grass all are lower than the level of 0.05-0.08%, and cordycepin content is higher during artificial culture.At present, content is arranged in the report pupa grass volvatus powder up to 1.0-5.0% or higher, so, limit raw material with cordycepin and help producing and implement, help reducing cost, meet the process of this technology.
Overcritical dioxy carbon extraction is meant under condition of high voltage and makes carbonic acid gas become liquid, as solvent, extracts composition stripping in still of Chinese medicinal materials.In carbonic acid gas flowed process, the pressure in the separating still, temperature difference analyzed required one-tenth, in conjunction with 1,2,3 separating stills or separation column a certain one-tenth are analyzed.Carbonic acid gas volatilization under reduced pressure can obtain deoxynucleoside component of the present invention or monomer, can extract once again in still blending ingredients (thick extract), and promptly with 50% or 70% crystallization, extraction once again.Also available common perfectly crystallization process obtains single component.Method of the present invention is characterized in that: adopt supercritical technology extraction deoxynucleoside effective constituents, extraction kettle pressure 15-50MPA; The separating still optimum pressure is 5-25MPA, but in the same flow process separating still pressure all the time less than extraction kettle pressure.In general, adopting carbon dioxide flow in extraction kettle is 15-25 liter/h, and the extraction kettle temperature is about 50-60 ℃.Separating still pressure, temperature are according to required condition changing.Experiment showed, that extraction temperature obviously do not destroy structures such as Chinese caterpillar fungus yet up to 100 ℃.
Description of drawings
The deoxynucleoside component that the present invention of being shown in Figure 1 makes, Chinese caterpillar fungus content is at 54.65% high pressure liquid chromatography figure.
The deoxynucleoside component that the present invention of being shown in Figure 2 makes, cordycepin content was at 75.18% o'clock high pressure liquid chromatography figure.The peak washes out the time at the 6.10-6.30 branch, and two peaks account for about 6.49% at the 4.20-4.60 branch; Three peaks accounted for 4.28% at 10.48 minutes; Four peaks accounted for about 4.23% at 7.78 minutes.
Fig. 3 is the UV spectrum feature of composition shown in Figure 2, and 217nm is 4.027; At 245nm one trough is arranged; Absorption peak is at 259nm.Wavelength when its absorbance is general is about 284nm.
Fig. 4 adopts 10% ethanol to make entrainment agent, the composition liquid chromatogram that is obtained; Main peak has only one, washes out 6.11 minutes time, accounts for 75.05%.
Fig. 5 is the ultraviolet spectrogram of Fig. 4: 219nm is 4.074, and 241nm trough absorbance is 1.68; The 259nm peak value is 2.045; The wavelength of peak value absorbancy one half is about 280nm.
Fig. 2,3 compares with Fig. 4,5, though main component is close all about 75%, because the super critical condition difference, the gained minor component has some differences; Liquid phase analysis changes on forming, and the peak height half-width of UV spectrum is slightly passed.Above-mentioned feature has constituted the fingerprint characteristic of present technique product, is different from single component or polycomponent that other method produces.When purity during in 95% left and right sides main peak have only one, the total value of all the other 4 absorption peaks is about 5%.When the standard substance of purity greater than 98% time, its ultraviolet feature is: trough is at 225-227nm, and peak value is at 259-260nm; Peak height half value wavelength is about 278nm.With the cordycepin monomer that supercritical technology obtains, its liquid chromatography has only 2-3 peak, and main peak＞98.6%, two peak, three peak sums are 1.4%.Different liquid chromatographs and elution requirement not simultaneously, gained peak position difference (washing out the time), available two kinds of samples merge and respectively sample introduction sweep figure, to show difference.The ultraviolet feature of present technique monomer product is: trough is at 227nm, and peak value is at 259nm; Half height is at 274nm.Because approach pure substance greater than 98%, monomer purity＞99.0%, liquid chromatography can show that a main peak is denoted as 100%, a minor component display waveform, and do not have score value.The two has many close parts with the traditional product comparison, but the waveform difference; Distinguished with infrared spectroscopy in case of necessity.
The present invention makes entrainment agent with ethanol, and alcohol concn is at 5-99%, up to adopting commercially available absolute alcohol to make entrainment agent.Optimum concn is the ethanol of 10%-30%.Ethanol, propane and water can be as entrainment agents, and propane has good development prospect, and that water is done entrainment agent institute is time-consuming longer.Owing to be that the solvent distribution principle is isolating, wait to improve so extract yield.In general, the preliminary experiment yield is 10-20%, improves experiment condition (time, flow, temperature, pressure and separation column carrier), can improve the product yield, thereby it is above or higher to reach 30-50%.Its principle makes up in this patent power scope.As adopt prolongation disengaging time, increasing pressure reduction, continuous several times extraction or adopt separation column etc.
Use carbon dioxide abstraction, structural similitude becomes branch to separate out in separating still, it can be multi-component mixture, but the main component cordycepin adopts this programme through flash liberation, can reach more than 50%, can meet two similar drug production requirements, handle through routine and just can carry out the new drug experimental study, establish industrialization for the product official listing and got production basis.
The deoxynucleoside component that in the invention process process, obtains, still be dissolved in the water, in the alcohol mixeding liquid or in the propane liquid, still need and adopt charcoal absorption, removal of impurities, organic solvent impurity elimination, recrystallization or ion exchange resin are handled impurity elimination, and lyophilize or vacuum-drying obtain powder raw material.Contain the powder raw material that cordycepin is 50-99.9% thereby become, assistant agent in addition produces tablet or capsule again, every contain 3 '-deoxynucleoside 5-200mg, best between 25-100mg.
With the deoxynucleoside meal that supercritical technology is produced, be processed into lyophilized injection, every cordycepin content 12.5-200mg, the best is propped up at 25-100mg/.
Said components has antitumor, and antiviral and immunoregulation effect also is the important reagent in genetically engineered field, also may become the auxiliary of treatment renal failure, therefore has broad application prospects.
Produce Chinese caterpillar fungus class deoxynucleoside with the technology of the present invention, have the following advantages: the Chinese caterpillar fungus class raw material that 1) has comprehensively used artificial culture; 2) improve industrial value; 3) supercritical technology is pollution-free, easily carries out; 4) do not damage the structure of active natural component; 5) has significant using value.
Embodiment
For embodiment the technology of the present invention process is described below:
Above-mentioned employing 2L extraction kettle obtains, can repeat the application of sample extraction or adopt 96 liters of equipment of pilot scale, can obtain more crystallizations, adopt ordinary method (Fan Biting chief editor: pharmacy of Chinese materia medica, Science and Technology of Shanghai press 1997 one edition, 348 pages, 401 pages), produce content at the 25mg/ sheet. and the conventional tablet or the capsule of grain.
The cordycepin monomer 500mg that adopts this law to make, be dissolved in the 50ml double distilled water, filter through glass filter G6, pack in the aseptic penicillin bottle, every bottle of 2.5ml handled through 24 hours on the Freeze Drying Equipment in sterilisable chamber, became platinum sponge shape object, seal, cordycepin lyophilized injection 25mg/ prop up.
Reference:
Chen Shunzhi, the infrared and ultraviolet spectrum characteristic of cordycepin, Chinese biochemical drug magazine, 1996.
Claims (7)
1, a kind of production method of super critical extracting caterpillar fungus oxygen nucleosides, it is characterized in that: with the fermented product after edible medicinal fungi Chinese caterpillar fungus or the Cordyceps militaris (L.) Link. artificial culture is raw material, adopt supercritical carbon dioxide extraction deoxynucleoside effective constituents, and obtain cordycepin as the entrainment agent decompression separation with ethanol, through traditional technology and then produce corresponding capsule, injection; The solid material granularity is the 20-60 order, and its content of cordycepin is at 0.8mg/g---18mg/g; Adopt supercritical carbon dioxide extraction deoxidation glycoside effective constituent, its extraction kettle pressure 15-50Mpa; Separating still pressure is 5-25Mpa, and the pressure of separating still is all the time less than the pressure of extraction kettle in the same flow process.
2, method according to claim 1 is characterized in that: adopt the solid of Chinese caterpillar fungus or Cordyceps militaris (L.) Link. artificial culture secondary fermentation thing or semi-solidly be raw material, comprise the surplus stock behind the super critical extracting caterpillar fungus oil, its water content is at 1-60%.
3, according to claim 1,2 described methods, it is characterized in that: the employing solid is a raw material, and its water content is 6-10%.
4, method according to claim 1 is characterized in that: make entrainment agent with ethanol, alcohol concn is at 5-99%.
5, method according to claim 1, it is characterized in that: the present invention separates the close several deoxynucleosides of acquisition composition, 3 '-deoxynucleoside, 3 '-amino-3 '-Desoxyadenosine, become the polycomponent thing, main component cordycepin 3 '-ratio of deoxynucleoside is between 30-99.9%.
6, method according to claim 1 is characterized in that: adopt the deoxynucleoside class powder raw material of supercritical technology preparation, be processed into tablet or capsule, every contain 3 '-deoxynucleoside 5-200mg between.
7, method according to claim 1 is characterized in that: the deoxynucleoside class powder raw material with the supercritical technology preparation, be processed into lyophilized injection, and every cordycepin content is 12.5-200mg.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011269103A CN1240706C (en) | 2001-09-28 | 2001-09-28 | Process for producing super critical extracting caterpillar fungus deoxynucleoside |
| PCT/CN2002/000683 WO2003028748A1 (en) | 2001-09-28 | 2002-09-27 | A method of extracting deoxyadenosins components from cordyceps sinensis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011269103A CN1240706C (en) | 2001-09-28 | 2001-09-28 | Process for producing super critical extracting caterpillar fungus deoxynucleoside |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1339440A CN1339440A (en) | 2002-03-13 |
| CN1240706C true CN1240706C (en) | 2006-02-08 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB011269103A Expired - Lifetime CN1240706C (en) | 2001-09-28 | 2001-09-28 | Process for producing super critical extracting caterpillar fungus deoxynucleoside |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN1240706C (en) |
| WO (1) | WO2003028748A1 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005030231A1 (en) * | 2003-09-28 | 2005-04-07 | Shaosheng Sun | The extractive of aweto and process for its preparation and uses |
| CN101124988B (en) * | 2007-09-25 | 2010-10-06 | 江苏瑞迪生科技有限公司 | Method for extracting refined cordycepin and cordycepin polysaccharide from cordyceps mititaris |
| CN101406491B (en) * | 2008-11-26 | 2011-04-06 | 吉林大学 | Oil-in-water Cordyceps sinensis emulsion and preparation technique |
| CN102349934B (en) * | 2011-10-24 | 2013-05-01 | 周伯扬 | Extraction process of effective ingredients from cordyceps mycelia |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1086732A (en) * | 1993-07-03 | 1994-05-18 | 李春燕 | North cordyceps extracting liquid and preparation method thereof |
| US5582828A (en) * | 1995-03-15 | 1996-12-10 | Ching-Yuang Lin | Active fractions of Cordyceps sinensis and method of isolation thereof |
-
2001
- 2001-09-28 CN CNB011269103A patent/CN1240706C/en not_active Expired - Lifetime
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2002
- 2002-09-27 WO PCT/CN2002/000683 patent/WO2003028748A1/en not_active Application Discontinuation
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| CN1339440A (en) | 2002-03-13 |
| WO2003028748A1 (en) | 2003-04-10 |
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