CN101156936B - An administer orally mixed nucleus glycosides as well as its preparing technics - Google Patents
An administer orally mixed nucleus glycosides as well as its preparing technics Download PDFInfo
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- CN101156936B CN101156936B CN2007100186227A CN200710018622A CN101156936B CN 101156936 B CN101156936 B CN 101156936B CN 2007100186227 A CN2007100186227 A CN 2007100186227A CN 200710018622 A CN200710018622 A CN 200710018622A CN 101156936 B CN101156936 B CN 101156936B
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Abstract
The invention belongs to the biology and pharmaceutical technical field, and relates to oral mixed nucleoside and the preparation process thereof. The invention mainly provides the oral mixed nucleoside and the preparation process thereof in order to overcome the problems existing in the prior art that the spatial structure of the product is damaged to a certain degree, the production cycle is longer, the operation is difficult, and the integrated cost is high. In order to overcome the problems existing in the prior art, the invention has the technical proposal that the oral mixed nucleoside is obtained through the following preparation processes, and the preparation processes comprise the steps that step one, malt roots are prepared; step two, pre-treatment: the malt roots are extracted through water, and filtered, after being preheated, phosphatase liquid is added to be prepared to be used; step three, hydrolytic reaction: purified water is preheated, and ribonucleic acid is added into the purified water, the pH value is adjusted, the mixed fluid in the step two is added into the purified water, the pH value is adjusted again, and the purified water is insulated and reacts; step four, the fluid is inactivated, the pH value is adjusted, and the fluid is filtered; step five, the fluid is concentrated and dried.
Description
Affiliated technical field:
The invention belongs to biological pharmacy technical field, relate to a kind of administer orally mixed nucleus glycosides as well and preparation technology thereof.
Background technology:
Nucleic acid is the base substance of life, and nucleotide is the main component of forming nucleic acid, and mixing the nucleoside main component is ribosidoadenine, guanosine, urine purine nucleoside, cytidine etc.Mix the nucleic acid metabolism that nucleoside can promote and improve human body, especially diseases such as chronic hepatitis, diabetes and cardiovascular thereof had unique curative effect, simultaneously, also have good antitumor and anticancer, raising immunologic function, expansion peripheral vessel and hypotensive effect.
Mixing nucleoside is a kind of nucleic acid class biochemical drug, and the preparation that mixes nucleoside in the prior art is that the ribonucleic acid (RNA) with animal is substrate, utilizes the method for physics and chemistry to decompose, and obtains to mix nucleoside.Its shortcoming is: 1, decomposition method is unreasonable, and the stereochemical structure that causes mixing nucleoside molecule is destroyed to a certain extent; 2, owing to production technology and step complexity, so the production cycle is long; 3, decomposition condition is required harshness, in actual production process, operation is difficulty relatively, technical level of operators is required high.4, adopt existing method, cost of material, running cost, technology cost etc. have caused the integrated cost of this method higher.
Summary of the invention:
The present invention will provide a kind of administer orally mixed nucleus glycosides as well and preparation technology thereof, and the product stereochemical structure that prior art exists is destroyed to a certain extent, the production cycle is long to overcome, operating difficulties and integrated cost problem of higher.
For overcoming the problem that prior art exists, technical scheme of the present invention is: a kind of administer orally mixed nucleus glycosides as well, obtain by following preparation technology, and described preparation technology comprises the steps successively
Step (one) preparation wheat root of the tooth;
Step (two) pretreatment: root of Cornu Cervi Pantotrichum water is carried, and filters, and adding phosphate enzyme liquid is standby after the preheating;
Step (three) hydrolysis: the purified water preheating, in purified water, add ribonucleic acid, adjust pH value, the mixed liquor that will go up step again adds, and adjusts pH value, insulation reaction;
Step (four): deactivation, adjust pH value, filter;
Step (five): concentrated, dry.
Above-mentioned steps also comprises the preparation processing step, and described preparation is oral solid preparation.
A kind of preparation technology of administer orally mixed nucleus glycosides as well comprises the steps: successively
Step (one) preparation wheat root of the tooth;
Step (two) pretreatment: root of Cornu Cervi Pantotrichum water is carried, and filters, and adding phosphate enzyme liquid is standby after the preheating;
Step (three) hydrolysis: the purified water preheating, in purified water, add ribonucleic acid, adjust pH value, the mixed liquor that will go up step again adds, and adjusts pH value, insulation reaction;
Step (four): deactivation, adjust pH value, filter;
Step (five): concentrated, dry.
In the above-mentioned steps (): select good Semen Tritici aestivi or Fructus Hordei Vulgaris, carry out remove impurity, soak cultivation in the ratio of wheat and water 1: 2～5 under 18～28 ℃ cultivation temperature, incubation time is 4～7 days.
In the above-mentioned steps (two), the parts by weight of root of Cornu Cervi Pantotrichum and purified water are 1: 8～12,10～25 ℃ of extraction temperatures, extraction time 10～26h, during filtration the elder generation press filtration, after carry out vacuum filtration; It is in 75 ± 2 ℃ the stainless steel cauldron behind preheating 30～55min that filtrate enters interlayer oil temperature, rapidly enzyme liquid is squeezed into mix homogeneously, and mixed liquor is standby.
In the above-mentioned steps (three), be preheated to 45～65 ℃ in the purified water adding stainless steel cauldron, purified water by weight: ribonucleic acid=20～25: 1 adds ribonucleic acid, stirring and dissolving, temperature is heated to 45～65 ℃, is that to regulate pH value be 4.5～7.0 for 20% sodium hydroxide solution with concentration then; The mixed liquor of step 2 is squeezed in the stainless steel cauldron, and transferring pH value is 5～6, is settled to 600L with purified water, fully mixes the back and stirs, and is heated to 60 ± 2 ℃, keeps thermotonus 2.5～3.5h.
In the above-mentioned steps (three), the stirring and dissolving speed after ribonucleic acid adds is 60～40 commentaries on classics/min, first quick and back slow; It is 10～20 commentaries on classics/min that mixed liquor adds the back mixing speed, and constant speed stirs.
In the above-mentioned steps (three), adopting high-temperature inactivation, is 20% sodium hydroxide solution accent pH value to 6.0～7.0 then with concentration, filters with 200 order filter clothes.
Adopt vacuum concentration mode, 50～65 ℃ of feed temperatures in the above-mentioned steps (four); Vacuum-0.084～-0.086Mpa; Stopping concentration is that content reaches 22～25%.
Above-mentioned steps also comprises the preparation processing step, and described preparation is oral solid preparation.
The present invention utilizes the biological decomposition method, with the organized enzyme in the root of Cornu Cervi Pantotrichum is reaction condition, under phosphoesterase action, ribonucleic acid (RNA) is degraded to the mixing nucleoside that main component is ribosidoadenine, guanosine, urine purine nucleoside, cytidine.
Compared with prior art, advantage of the present invention is:
1, the product stereochemical structure is kept perfectly, biological activity height, quality better.
2, with short production cycle: it is the basic condition of decomposition reaction that the present invention adopts the organized enzyme in the root of Cornu Cervi Pantotrichum, carries out biological decomposition, and the cycle is short, only needs about one day time, and the equipment operation cycle shortens
3, process conditions are clear and definite easy to operate, to operator's requirement reduction.
4, adopt first among the present invention with the catalyzing enzyme system of root of Cornu Cervi Pantotrichum as the product decomposition, utilize biological method to decompose substrate, the requirement reduction to equipment makes integrated cost of the present invention reduce.
5, no high-risk step in the whole processing step is safe and reliable.
The specific embodiment:
To be described in detail the present invention by specific embodiment below.
Embodiment 1:
Step (one) preparation wheat root of the tooth: select good Semen Tritici aestivi or Fructus Hordei Vulgaris, carry out remove impurity, soak cultivation in wheat and 1: 2 ratio of water under 18 ℃ cultivation temperature, incubation time is 7 days;
Step (two): pretreatment
Water is carried: root of Cornu Cervi Pantotrichum is put into leaching tank, add the purified water lixiviate.
Operating process:
The 48Kg root of Cornu Cervi Pantotrichum is put into 12 stainless steel casks by the 4Kg/ bucket respectively, then the 480Kg purified water is joined in 12 stainless steel casks and carry out lixiviate, the parts by weight of root of Cornu Cervi Pantotrichum and purified water are 1: 10,10 ℃ of extraction temperatures, extraction time 25h, earlier soaked root of Cornu Cervi Pantotrichum solution is carried out press filtration with 60 order filter clothes during filtration, reuse 200 order filter clothes carried out vacuum filtration after filtrate was left standstill 90min; It is in 75 ± 2 ℃ the stainless steel cauldron behind the preheating 30min that filtrate enters interlayer oil temperature, rapidly enzyme liquid is squeezed in the stainless steel cauldron, and mix homogeneously, mixed liquor is standby.
Step (three): hydrolysis
(1) will be preheated to 45 ℃ in the 250L purified water adding 1000L stainless steel cauldron.
(2) 12Kg ribonucleic acid is dissolved in the 1000L stainless steel cauldron, mixing speed is 60 commentaries on classics/min, is adjusted to 45 commentaries on classics/min subsequently, keeps about 45 ℃; Be that to regulate pH value be 5.1 for 20% sodium hydroxide solution with concentration then.
(3) mixed liquor of step (two) is squeezed in the 1000L stainless steel cauldron, transferring pH value is 6.4, is settled to 600L with purified water, fully mixes the back and regulates mixing speed to 15 commentaries on classics/min, is heated to 60 ± 2 ℃, keeps thermotonus 3h.The zymolysis of utilization phosphate is degraded to the mixing nucleoside that main component is ribosidoadenine, guanosine, urine purine nucleoside, cytidine with macromole ribonucleic acid (RNA).
Step (four): deactivation and PH regulate
After hydrolysis finishes, beginning to heat up and boil 10min, is that 20% sodium hydroxide solution is transferred pH value to 7.0 with concentration, with 200 order filter clothes filtration enzymolysis solution.
Step (five): concentrated, dry.
Spissated specific operation process is as follows:
(1) opens vacuum system, will filter enzymolysis solution and be pumped in the concentration tank, add earlier for the first time about 300L, later on along with the minimizing that concentrates volume replenishes again.
(2) in the concentration tank temperature be controlled at 55 ± 2 ℃/vacuum-0.084～-0.086Mpa, the temperature control of interlayer oil is about 130 ± 5 ℃, when concentrated volume during less than 200L, the temperature control of perusal interlayer oil is about 100 ℃, in case concentrate feed liquid knot rice crust in the later stage jar.
(3) concentration time is 14～18h.
(4) sampling detectable concentration during concentration time to 14～18 hour finishes when concentration concentrates 22～25% the time.
(5) concentrate to finish after 200 order filter clothes are squeezed into the heat insulated tank on the spray tower after filtering.
Step (six): preparation processing step.The product that top step is made galenic pharmacy method routinely is prepared into tablet.
Embodiment 2:
Step (one) preparation wheat root of the tooth: select good Semen Tritici aestivi or Fructus Hordei Vulgaris, carry out remove impurity, soak cultivation in wheat and 1: 5 ratio of water under 28 ℃ cultivation temperature, incubation time is 4 days;
Step (two): pretreatment
Water is carried: root of Cornu Cervi Pantotrichum is put into leaching tank, add the purified water lixiviate.
Operating process: the 48Kg root of Cornu Cervi Pantotrichum is put into 12 stainless steel casks by the 4Kg/ bucket respectively, then the 570Kg purified water is joined in 12 stainless steel casks and carry out lixiviate, 25 ℃ of extraction temperatures, extraction time 10h, earlier soaked root of Cornu Cervi Pantotrichum solution is carried out press filtration with 60 order filter clothes during filtration, reuse 200 order filter clothes carried out vacuum filtration after filtrate was left standstill 70min; It is in 75 ± 2 ℃ the stainless steel cauldron behind the preheating 50min that filtrate enters interlayer oil temperature, rapidly enzyme liquid is squeezed in the stainless steel cauldron, and mix homogeneously, mixed liquor is standby.
Step (three): hydrolysis
(1) will be preheated to 60 ℃ in the 250L purified water adding 1000L stainless steel cauldron.
(2) 10Kg ribonucleic acid is dissolved in the 1000L stainless steel cauldron, mixing speed is 60 commentaries on classics/min, is adjusted to 40 commentaries on classics/min subsequently, keeps about 60 ℃; Be that to regulate pH value be 7.0 for 20% sodium hydroxide solution with concentration then.Stirring and dissolving speed after ribonucleic acid adds is 60～40 commentaries on classics/min, first quick and back slow; It is 20 commentaries on classics/min that mixed liquor adds the back mixing speed, and constant speed stirs.
(3) mixed liquor of step (two) is squeezed in the 1000L stainless steel cauldron, transferring pH value is 6, is settled to 600L with purified water, fully mixes the back and regulates mixing speed to 20 commentaries on classics/min, is heated to 60 ± 2 ℃, keeps thermotonus 2.5h.The zymolysis of utilization phosphate is degraded to the mixing nucleoside that main component is ribosidoadenine, guanosine, urine purine nucleoside, cytidine with macromole ribonucleic acid (RNA).
Step (four): deactivation and PH regulate
After hydrolysis finishes, beginning to heat up and boil 10min, is that 20% sodium hydroxide solution is transferred pH value to 6.0 with concentration, with 200 order filter clothes filtration enzymolysis solution.
Step (five): concentrated, dry.
The concentration operation process is with embodiment 1.
Step (six): preparation processing step.The product that top step is made galenic pharmacy method routinely is prepared into capsule and dissolved granule.
Simultaneously, the present invention is according to absorption of human body and metabolism characteristics, determined that absorption of human body utilizes the dosage form and the dose of administer orally mixed nucleus glycosides as well medicine.Dose is: 0.05 gram～3.0 grams.(child's consumption 0.05～2 gram, adult's consumption 0.1～3.0 gram)
Claims (8)
1. an administer orally mixed nucleus glycosides as well is obtained by following preparation technology, and described preparation technology comprises the steps successively
Step (one) preparation wheat root of the tooth;
Step (two) pretreatment: root of Cornu Cervi Pantotrichum water is carried, and filters, and it is standby to add phosphate enzyme liquid after being preheated to 75 ± 2 ℃;
Step (three) hydrolysis: purified water is preheated to 45 ℃-65 ℃, adds ribonucleic acid in purified water, adjusts pH value to 4.5-7.0, and the mixed liquor that will go up step again adds, and adjusts pH value to 5-6, is heated to 60 ± 2 ℃ of insulation reaction;
Step (four): deactivation, adjust pH value to 6.0-7.0, filter;
Step (five): concentrated, dry.
2. the preparation technology of a kind of administer orally mixed nucleus glycosides as well as claimed in claim 1 comprises the steps: successively
Step (one) preparation wheat root of the tooth;
Step (two) pretreatment: root of Cornu Cervi Pantotrichum water is carried, and filters, and it is standby to add phosphate enzyme liquid after 75 ± 2 ℃ of the preheatings;
Step (three) hydrolysis: 45 ℃-65 ℃ of purified water preheatings, in purified water, add ribonucleic acid, adjust pH value to 4.5-7.0, the mixed liquor that will go up step again adds, and adjusts pH value to 5-6, is heated to 60 ± 2 ℃ of insulation reaction;
Step (four): deactivation, adjust pH value to 6.0-7.0, filter;
Step (five): concentrated, dry.
3. the preparation technology of a kind of administer orally mixed nucleus glycosides as well as claimed in claim 3, it is characterized in that: in the described step (two), the parts by weight of root of Cornu Cervi Pantotrichum and purified water are 1: 8～12,10～25 ℃ of extraction temperatures, extraction time 10～26h, during filtration the elder generation press filtration, after carry out vacuum filtration; It is in 75 ± 2 ℃ the stainless steel cauldron behind preheating 30～55min that filtrate enters interlayer oil temperature, rapidly enzyme liquid is squeezed into mix homogeneously, and mixed liquor is standby.
4. as the preparation technology of claim 2 or 3 described a kind of administer orally mixed nucleus glycosides as well, it is characterized in that: in the described step (three), be preheated to 45～65 ℃ in the purified water adding stainless steel cauldron, purified water by weight: ribonucleic acid=20～25: 1 adds ribonucleic acid, stirring and dissolving, temperature is heated to 45～65 ℃, is that to regulate pH value be 4.5～7.0 for 20% sodium hydroxide solution with concentration then; The mixed liquor of step (two) is squeezed in the stainless steel cauldron, and transferring pH value is 5～6, is settled to 600L with purified water, fully mixes the back and stirs, and is heated to 60 ± 2 ℃, keeps thermotonus 2.5～3.5h.
5. the preparation technology of a kind of administer orally mixed nucleus glycosides as well as claimed in claim 4 is characterized in that: in the described step (three), the stirring and dissolving speed after ribonucleic acid adds is 60～40 commentaries on classics/min, first quick and back slow; It is 10～20 commentaries on classics/min that mixed liquor adds the back mixing speed, and constant speed stirs.
6. the preparation technology of a kind of administer orally mixed nucleus glycosides as well as claimed in claim 5, it is characterized in that: in the described step (): select good Semen Tritici aestivi or Fructus Hordei Vulgaris, carry out remove impurity, soak cultivation in the ratio of wheat and water 1: 2～5 under 18～28 ℃ cultivation temperature, incubation time is 4～7 days.
7. the preparation technology of a kind of administer orally mixed nucleus glycosides as well as claimed in claim 6 is characterized in that: in the described step (four), adopting high-temperature inactivation, is 20% sodium hydroxide solution accent pH value to 6.0～7.0 then with concentration, filters with 200 order filter clothes.
8. the preparation technology of a kind of administer orally mixed nucleus glycosides as well as claimed in claim 7 is characterized in that adopting in the described step (five) vacuum concentration mode, 50～65 ℃ of feed temperatures; Vacuum-0.084～-0.086Mpa; Stopping concentration is that content reaches 22～25%.
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Non-Patent Citations (3)
| Title |
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| 段作营,刘军昌,于瑞嵩,毛忠贵.《麦芽根中5_磷酸二脂酶的提取及制备》.《中国调味品》.2003,(第2期),36-39. * |
| 陈洁,王璋.《麦芽根中核酸酶的提取及制备》.《食品工业科技》.2000,第21卷(第1期),19-21. * |
| 陈洁，王璋.《麦芽根的综合利用研究进展》.《食品工业科技》.1999,第20卷(第5期),61-63. * |
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