CN103976981B - A kind of cordycepin nano controlled-release capsule and preparation method thereof - Google Patents
A kind of cordycepin nano controlled-release capsule and preparation method thereof Download PDFInfo
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Abstract
A kind of cordycepin nano controlled-release capsule and preparation method thereof, relates to medicine and pharmaceutical intermediate compound modification field, solves the half-life occurred during existing cordycepin uses short problem.Cordycepin solution is obtained by cordycepin being dissolved in weakly acidic solution, sodium alginate is dissolved in alkaline solution and obtains sodium alginate soln, it is that 1:10～10:1 mixes at least 20min by above-mentioned solution by cordycepin and the mol ratio of sodium alginate, cordycepin nano controlled-release ball is obtained, by the CaCl of cordycepin nano controlled-release ball Yu 0.125mol/L by centrifugation after washing, ultrasonic disperse2After solution equal-volume is mixing cured, obtain the cordycepin nano controlled-release capsule powder of a diameter of 200nm～300nm.The present invention, by cordycepin solution and sodium alginate soln mixing method, uses CaCl simultaneously2Curing technology, technological process is workable, has good cordycepin sustained release performance and fungistatic effect, and bacteriostasis rate can reach 70%.
Description
Technical field
The present invention relates to medicine and pharmaceutical intermediate compound technical field of modification, be specifically related to a kind of cordycepin nanometer
Slow release capsule and preparation method thereof.
Background technology
Cordycepin is also known as cordycepin, cordycepin, 3'-Deoxyadenosine, and it is first and separates from fungus
Ucleosides antibiotics.Its molecular formula is C10H13N5O3, molecular weight is 25l.24, and fusing point 230～23l DEG C are dissolved in water, hot ethanol
And methanol, insoluble in benzene, ether and chloroform, a length of 259nm of maximum absorption wave of ultraviolet light.Cordyceps have antitumor, anti-white blood
Many pharmacological actions such as sick, antibacterial, immunomodulating, removing interior free yl.According to another report, cordycepin on the one hand have right
DNA and RNA building-up process, add three aspects such as RNA and mRNA posttranscriptional modification process and adenyl cyclase activation suppression make
With, on the other hand it can promote that again cell breaks up, reconstituted cell skeleton.Cordyceps have reduction cholesterol, blood sugar lowering, infection,
Antiplasmodial, the effect of anti-mosquito, the cordyceps sinensis fermentation liquor containing cordycepin is to asthma and disease of bronchus, the kidney merit of person having renal failure
The aspects such as energy have good adjuvant treatment effect.
At present, cordycepin is degraded through deamination in vivo, causes the internal use half-life short.Research worker
General anti-deamination protective agent and cordycepin is used to join and use, the problem that half-life that solution cordycepin deamination causes is short.But,
In cordycepin body, deamination reaction belongs to normal physiological metabolism, and the protectant use of anti-deamination can cause other normal deamination simultaneously
Degradation pathway is abnormal, affects the physiological process of body.Meanwhile, the existing protectant limited use of anti-deamination, it is impossible at all extend
The cordycepin half-life.
Modern nano controlled-release drug technique is extending small-molecule drug half-life, reduction drug side effect, targeted therapy, is carrying
The aspects such as high curative effect of medication have huge advantage.At present, the report of cordycepin nano controlled-release capsule is not prepared in discovery.
Summary of the invention
For the problem that the half-life occurred during solving cordycepin use is short, the present invention provides a kind of cordycepin nanometer
Slow release capsule and preparation method thereof.
The present invention solves that the technical scheme that technical problem is used is as follows:
A kind of cordycepin nano controlled-release capsule of the present invention, obtains 100mol/L Cordyceps by cordycepin is dissolved in weakly acidic solution
Cellulose solution, is dissolved in sodium alginate alkaline solution and obtains 1mol/L sodium alginate soln, under the conditions of 20 DEG C～40 DEG C, by above-mentioned two
Kind of solution is that 1:10～10:1 ratio mixes at least 20min in cordycepin and the mol ratio of sodium alginate, washs by centrifugation, ultrasonic
Cordycepin nano controlled-release ball is obtained, by the CaCl of this cordycepin nano controlled-release ball Yu 0.125mol/L after dispersion2Solution equal-volume mixes
After closing solidification, wash, obtain after drying the cordycepin nano controlled-release capsule powder of a diameter of 200nm～300nm by centrifugation.
Described weakly acidic solution is through water-reducible 1% formic acid of deionization, 1% acetic acid, 0.5% phosphoric acid, 1% citric acid
Or 0.5% boric acid；Described alkaline solution is 1%KOH solution or 1%NaOH solution.
Described cordycepin is purchased from Sigma, and purity is 99.9%.
The present invention also provides for the preparation method of a kind of cordycepin nano controlled-release capsule, following steps realize:
(1) cordycepin is dissolved in weakly acidic solution, obtains the cordycepin solution that concentration is 100mol/L；Described weak acid
Property solution is through water-reducible 1% formic acid of deionization, 1% acetic acid, 0.5% phosphoric acid, 1% citric acid or 0.5% boric acid, preferably
1% acetic acid；
(2) sodium alginate is dissolved in alkaline solution, obtains the sodium alginate soln that concentration is 1mol/L；Described alkalescence
Solution is 1%KOH solution or 1%NaOH solution；
(3) sodium alginate soln that cordycepin solution step (1) obtained and step (2) obtain is according to cordycepin and sea
The mol ratio of sodium alginate is that the ratio of 1:10～10:1 (preferred molar ratio is 5:1,10:1) mixes at least 20min, by centrifugation, washes
Wash, obtain cordycepin nano controlled-release ball after ultrasonic disperse；Described cordycepin solution is 20 with the mixing temperature of sodium alginate soln
DEG C～40 DEG C；
(4) cordycepin nano controlled-release ball step (3) obtained and concentration are the CaCl of 0.125mol/L2Solution equal-volume
Mixing, after solidification, by centrifugation, washing, obtains the cordycepin nano controlled-release capsule powder of a diameter of 200nm～300nm after drying；
Described cordycepin nano controlled-release ball and CaCl2Incorporation time 10min of solution～20min.
The invention has the beneficial effects as follows: the present invention use sodium alginate as carrier material, by cordycepin solution and sea
Solution of sodium alginate mixing method, to protect cordycepin activity, to make it preferably play antibacterial action；Use CaCl simultaneously2Solidification skill
Art, CaCl2The concentration of solution is set in 0.125mol/L, and technological process is workable, it is easy to batch production, through test, this
The cordycepin nano controlled-release capsule particle size range that invention obtains is 200nm～300nm, has good cordycepin sustained release performance and presses down
Bacterium effect, bacteriostasis rate can reach 70%.
Accompanying drawing explanation
Fig. 1 is the scanning electron microscope detection figure of the cordycepin nano controlled-release capsule obtained in embodiment 1.
Fig. 2 is the cordycepin release profiles schematic diagram of the cordycepin nano controlled-release capsule obtained in embodiment 1；A line represents warp
CaCl2The cordycepin release profiles of solution cured cordycepin nano controlled-release capsule；B line represents and is provided without CaCl2Solution cured worm
The cordycepin release profiles of grass element nano controlled-release capsule.
Fig. 3 is the fungistatic effect figure of the cordycepin nano controlled-release capsule obtained in embodiment 1；Fig. 3 A is bacillus subtilis
Antibacterial situation, Fig. 3 B is colibacillary antibacterial situation.
Fig. 4 is the scanning electron microscope detection figure of the cordycepin nano controlled-release capsule obtained in embodiment 2.
Fig. 5 is the scanning electron microscope detection figure of the cordycepin nano controlled-release capsule obtained in embodiment 3.
Fig. 6 is the scanning electron microscope detection figure of the cordycepin nano controlled-release capsule obtained in embodiment 4.
Fig. 7 is the scanning electron microscope detection figure of the cordycepin nano controlled-release capsule obtained in embodiment 5.
Fig. 8 is the cordycepin release profiles schematic diagram of the cordycepin nano controlled-release capsule obtained in embodiment 2,3,4,5；A line
Representing the cordycepin release profiles schematic diagram in embodiment 2, B line represents the cordycepin release profiles schematic diagram in embodiment 3, C
Line represents the cordycepin release profiles schematic diagram in embodiment 4, and D line represents cordycepin release profiles schematic diagram.
Fig. 9 is the fungistatic effect figure of the cordycepin nano controlled-release capsule obtained in embodiment 2；Fig. 9 A is bacillus subtilis
Antibacterial situation (374 bacterium colonies), Fig. 9 B is colibacillary antibacterial situation (249 bacterium colonies).
Figure 10 is the fungistatic effect figure of the cordycepin nano controlled-release capsule obtained in embodiment 3,4,5；Figure 10 A is embodiment 3
In the cordycepin nano controlled-release capsule that obtains to colibacillary fungistatic effect figure, Figure 10 B is that the cordycepin obtained in embodiment 4 is received
Rice slow release capsule is to colibacillary fungistatic effect figure, and Figure 10 C is that in embodiment 5, cordycepin nano controlled-release capsule presses down colibacillary
Bacterium design sketch.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described in further detail.
Embodiment 1
(1) by being dissolved in 1% acetic acid (deionized water dilution) purchased from the cordycepin of Sigma, purity 99.9%, obtain dense
Degree is the cordycepin solution of 100mol/L；
(2) sodium alginate is dissolved in 1%NaOH solution, obtains the sodium alginate soln that concentration is 1mol/L；
(3) the 100mol/L cordycepin solution that 1mol/L sodium alginate soln step (2) obtained obtains to step (1)
Middle dropping, according to the alginic acid contained in the cordycepin contained in 100mol/L cordycepin solution and 1mol/L sodium alginate soln
The mol ratio of sodium is the ratio mixing of 10:1, and under the conditions of 25 DEG C, mixing 20min, 1000rpm are centrifugal abandons supernatant, precipitation deionization
Water 1% dilutes, ultrasonic disperse 20min, repeated centrifugation, deionized water wash and ultrasonic disperse process three times, obtains cordycepin and receives
Rice sustained-release microspheres；
(4) the cordycepin nano controlled-release ball deionized water 1% step (3) obtained dilutes, ultrasonic disperse, then with concentration
CaCl for 0.125mol/L2Solution equal-volume mixes, and is slowly stirred 10min, centrifuge washing three times, drying after solidification
After obtain cordycepin nano controlled-release capsule powder；
(5) cordycepin nano controlled-release capsule powder step (4) obtained carries out Flied emission environmental scanning electron microscope
Detection, measures its diameter and is about 200nm, as shown in Figure 1.
(6) weigh the cordycepin nano controlled-release capsule powder 1g that step (4) obtains to be placed in container, add 100ml concentration
For 0.2mol/L phosphate buffer (pH7.0), under the conditions of 37 DEG C of lucifuges, shaking table 100rpm discharges；1h, 4h, 8h,
12h, 18h, 24h, 48h time point respectively takes out 1 pipe sample, and 15000rpm is centrifuged 20min, takes supernatant, and spectrophotography 260nm surveys
Determine cordycepin concentration.
Result is as shown in Figure 2: the cordycepin release of averagely only about 40% during 24h, still has about 60% Cordyceps after 48h
Element is retained in sodium alginate nanoparticles, and cordycepin slowly discharges (see A line in Fig. 2)；And it is provided without CaCl2Solution cured worm
Grass element nano controlled-release capsule discharges about 45% cordycepin within 0.5h, and within 8h, cordycepin release reaches 90% (see B in Fig. 2
Line).Illustrate to use CaCl2Solution cured cordycepin nano controlled-release capsule can keep more preferable stability.
(7) cordycepin nano controlled-release capsule powder step (4) obtained is dissolved in 5% (mass/volume) ratio
In ionized water, coat the latter half (the microorganism plating medium the latter half coating Cordyceps on microorganism plating medium
Element nano controlled-release capsule, top half blank are not coated with cordycepin nano controlled-release capsule as comparison), by bacterium solution (the hay spore of dilution
Bacillus and escherichia coli) it is spread evenly across on microorganism plating medium cultivation.
Result is as shown in Figure 3: Fig. 3 A is the antibacterial situation of bacillus subtilis, and Fig. 3 B is colibacillary antibacterial situation,
Top half uncoated cordycepin nano controlled-release capsule, the latter half coating cordycepin nano controlled-release capsule；Top half bacterium colony in flakes,
The latter half bacterium colony is sparse.Either bacillus subtilis or escherichia coli, the most substantially suppressed, cordycepin nano controlled-release
Capsule has good bacteriostasis, estimates bacillus subtilis and colibacillary bacteriostasis rate by colony counting method, reaches respectively
To 68% and 70%.
Embodiment 2
(1) by being dissolved in 1% formic acid (deionized water dilution) purchased from the cordycepin of Sigma, purity 99.9%, obtain dense
Degree is the cordycepin solution of 100mol/L；
(2) sodium alginate is dissolved in 1%KOH solution, obtains the sodium alginate soln that concentration is 1mol/L；
(3) the 100mol/L cordycepin solution that 1mol/L sodium alginate soln step (2) obtained obtains to step (1)
Middle dropping, according to the alginic acid contained in the cordycepin contained in 100mol/L cordycepin solution and 1mol/L sodium alginate soln
The mol ratio of sodium is the ratio mixing of 5:1, and under the conditions of 20 DEG C, mixing 30min, 1000rpm are centrifugal abandons supernatant, precipitation deionization
Water 1% dilutes, ultrasonic disperse 20min, repeated centrifugation, deionized water wash and ultrasonic disperse process three times, obtains cordycepin and receives
Rice sustained-release microspheres；
(4) the cordycepin nano controlled-release ball deionized water 1% step (3) obtained dilutes, ultrasonic disperse, then with concentration
CaCl for 0.125mol/L2Solution equal-volume mixes, and is slowly stirred 20min, centrifuge washing three times after solidification, after drying
To cordycepin nano controlled-release capsule powder；
(5) cordycepin nano controlled-release capsule powder step (4) obtained carries out Flied emission environmental scanning electron microscope
Detection, measures its a diameter of 200nm, as shown in Figure 4.
(6) weigh the cordycepin nano controlled-release capsule powder 1g that step (4) obtains to be placed in container, add 100ml concentration
For 0.2mol/L phosphate buffer (pH7.0), under the conditions of 37 DEG C of lucifuges, shaking table 100rpm discharges；1h, 4h, 8h,
12h, 18h, 24h, 48h time point respectively takes out 1 pipe sample, and 15000rpm is centrifuged 20min, takes supernatant, and spectrophotography 260nm surveys
Determine cordycepin concentration.
Result is as shown in A line in Fig. 8: the cordycepin release of averagely only about 33% during 24h, still has about after 48h
65% cordycepin is retained in sodium alginate nanoparticles, and cordycepin slowly discharges.
(7) cordycepin nano controlled-release capsule powder step (4) obtained is dissolved in 5% (mass/volume) ratio
In ionized water, coat on microorganism plating medium, the bacterium solution (bacillus subtilis and escherichia coli) of dilution is uniformly coated with
It is distributed on microorganism plating medium cultivation.
Result is as it is shown in figure 9, antibacterial situation (comprising 374 bacterium colonies) that Fig. 9 A is bacillus subtilis, and Fig. 9 B is large intestine
Bacillus antibacterial situation (comprising 249 bacterium colonies)；Either bacillus subtilis or escherichia coli, the most substantially pressed down
System, cordycepin nano controlled-release capsule has good bacteriostasis, estimates bacillus subtilis and large intestine bar by colony counting method
The bacteriostasis rate of bacterium, respectively reaches 65% and 69%.
Embodiment 3
(1) by being dissolved in 0.5% boric acid (deionized water dilution) purchased from the cordycepin of Sigma, purity 99.9%, obtain
Concentration is the cordycepin solution of 100mol/L；
(2) sodium alginate is dissolved in 1%KOH solution, obtains the sodium alginate soln that concentration is 1mol/L；
(3) the 100mol/L cordycepin solution that 1mol/L sodium alginate soln step (2) obtained obtains to step (1)
Middle dropping, according to the alginic acid contained in the cordycepin contained in 100mol/L cordycepin solution and 1mol/L sodium alginate soln
The mol ratio of sodium is the ratio mixing of 1:5, and under the conditions of 30 DEG C, mixing 30min, 1000rpm are centrifugal abandons supernatant, precipitation deionization
Water 1% dilutes, ultrasonic disperse 20min, repeated centrifugation, deionized water wash and ultrasonic disperse process three times, obtains cordycepin and receives
Rice sustained-release microspheres；
(4) the cordycepin nano controlled-release ball deionized water 1% step (3) obtained dilutes, ultrasonic disperse, then with concentration
CaCl for 0.125mol/L2Solution equal-volume mixes, and is slowly stirred 20min, centrifuge washing three times after solidification, after drying
To cordycepin nano controlled-release capsule powder；
(5) cordycepin nano controlled-release capsule powder step (4) obtained carries out Flied emission environmental scanning electron microscope
Detection, measures its a diameter of 300nm, as shown in Figure 5.
(6) weigh the cordycepin nano controlled-release capsule powder 1g that step (4) obtains to be placed in container, add 100ml concentration
For 0.2mol/L phosphate buffer (pH7.0), under the conditions of 37 DEG C of lucifuges, shaking table 100rpm discharges；1h, 4h, 8h,
12h, 18h, 24h, 48h time point respectively takes out 1 pipe sample, and 15000rpm is centrifuged 20min, takes supernatant, and spectrophotography 260nm surveys
Determine cordycepin concentration.
Result is as shown in B line in Fig. 8: the cordycepin release of averagely only about 30% during 24h, still has about after 48h
70% cordycepin is retained in sodium alginate nanoparticles, and cordycepin slowly discharges.
(7) cordycepin nano controlled-release capsule powder step (4) obtained is dissolved in 5% (mass/volume) ratio
In ionized water, coat on microorganism plating medium, the Escherichia coli bacteria liquid of dilution is spread evenly across the training of microorganism flat board
Support and cultivate on base.
Result is as shown in Figure 10 A: escherichia coli are substantially suppressed, and cordycepin nano controlled-release capsule has good antibacterial energy
Power, estimates escherichia coli bacteriostasis rate by colony counting method, reaches 60%.
Embodiment 4
(1) by being dissolved in 1% citric acid (deionized water dilution) purchased from the cordycepin of Sigma, purity 99.9%, obtain
Concentration is the cordycepin solution of 100mol/L；
(2) sodium alginate is dissolved in 1%NaOH solution, obtains the sodium alginate soln that concentration is 1mol/L；
(3) the 100mol/L cordycepin solution that 1mol/L sodium alginate soln step (2) obtained obtains to step (1)
Middle dropping, according to the alginic acid contained in the cordycepin contained in 100mol/L cordycepin solution and 1mol/L sodium alginate soln
The mol ratio of sodium is the ratio mixing of 1:1, and under the conditions of 25 DEG C, mixing 20min, 1000rpm are centrifugal abandons supernatant, precipitation deionization
Water 1% dilutes, ultrasonic disperse 20min, repeated centrifugation, deionized water wash and ultrasonic disperse process three times, obtains cordycepin and receives
Rice sustained-release microspheres；
(4) the cordycepin nano controlled-release ball deionized water 1% step (3) obtained dilutes, ultrasonic disperse, then with concentration
CaCl for 0.125mol/L2Solution equal-volume mixes, and is slowly stirred 10min, centrifuge washing three times after solidification, after drying
To cordycepin nano controlled-release capsule powder；
(5) cordycepin nano controlled-release capsule powder step (4) obtained carries out Flied emission environmental scanning electron microscope
Detection, measures its a diameter of 300nm, as shown in Figure 6.
(6) weigh the cordycepin nano controlled-release capsule powder 1g that step (4) obtains to be placed in container, add 100ml concentration
For 0.2mol/L phosphate buffer (pH7.0), under the conditions of 37 DEG C of lucifuges, shaking table 100rpm discharges；1h, 4h, 8h,
12h, 18h, 24h, 48h time point respectively takes out 1 pipe sample, and 15000rpm is centrifuged 20min, takes supernatant, and spectrophotography 260nm surveys
Determine cordycepin concentration.
Result is as shown in C line in Fig. 8: the cordycepin release of averagely only about 28% during 24h, still has about after 48h
70% cordycepin is retained in sodium alginate nanoparticles, and cordycepin slowly discharges.
(7) cordycepin nano controlled-release capsule powder step (4) obtained is dissolved in 5% (mass/volume) ratio
In ionized water, coat on microorganism plating medium, the Escherichia coli bacteria liquid of dilution is spread evenly across the training of microorganism flat board
Support and cultivate on base.
Result is as shown in Figure 10 B: escherichia coli are substantially suppressed, and cordycepin nano controlled-release capsule has good antibacterial energy
Power, estimates colibacillary bacteriostasis rate by colony counting method, reaches 61%.
Embodiment 5
(1) by being dissolved in 0.5% phosphoric acid (deionized water dilution) purchased from the cordycepin of Sigma, purity 99.9%, obtain
Concentration is the cordycepin solution of 100mol/L；
(2) sodium alginate is dissolved in 1%NaOH solution, obtains the sodium alginate soln that concentration is 1mol/L；
(3) the 100mol/L cordycepin solution that 1mol/L sodium alginate soln step (2) obtained obtains to step (1)
Middle dropping, according to the alginic acid contained in the cordycepin contained in 100mol/L cordycepin solution and 1mol/L sodium alginate soln
The mol ratio of sodium is the ratio mixing of 1:10, and under the conditions of 25 DEG C, mixing 20min, 1000rpm are centrifugal abandons supernatant, precipitation deionization
Water 1% dilutes, ultrasonic disperse 20min, repeated centrifugation, deionized water wash and ultrasonic disperse process three times, obtains cordycepin and receives
Rice sustained-release microspheres；
(4) the cordycepin nano controlled-release ball deionized water 1% step (3) obtained dilutes, ultrasonic disperse, then with concentration
CaCl for 0.125mol/L2Solution equal-volume mixes, and is slowly stirred 10min, centrifuge washing three times after solidification, after drying
To cordycepin nano controlled-release capsule powder；
(5) cordycepin nano controlled-release capsule powder step (4) obtained carries out Flied emission environmental scanning electron microscope
Detection, measures its a diameter of 200nm, as shown in Figure 7.
(6) weigh the cordycepin nano controlled-release capsule powder 1g that step (4) obtains to be placed in container, add 100ml concentration
For 0.2mol/L phosphate buffer (pH7.0), under the conditions of 37 DEG C of lucifuges, shaking table 100rpm discharges；1h, 4h, 8h,
12h, 18h, 24h, 48h time point respectively takes out 1 pipe sample, and 15000rpm is centrifuged 20min, takes supernatant, and spectrophotography 260nm surveys
Determine cordycepin concentration.
Result is as shown in D line in Fig. 8: the cordycepin release of averagely only about 25% during 24h, still has about after 48h
70% cordycepin is retained in sodium alginate nanoparticles, and cordycepin slowly discharges.
(7) cordycepin nano controlled-release capsule powder step (4) obtained is dissolved in 5% (mass/volume) ratio
In ionized water, coat on microorganism plating medium, the Escherichia coli bacteria liquid of dilution is spread evenly across the training of microorganism flat board
Support and cultivate on base.
Result is as illustrated in figure 10 c: escherichia coli are substantially suppressed, and cordycepin nano controlled-release capsule has good antibacterial energy
Power, estimates escherichia coli bacteriostasis rate by colony counting method, reaches 58%.
Claims (10)
1. a cordycepin nano controlled-release capsule, it is characterised in that obtain 100mol/L worm by cordycepin being dissolved in weakly acidic solution
Grass cellulose solution, is dissolved in sodium alginate alkaline solution and obtains 1mol/L sodium alginate soln, under the conditions of 20 DEG C～40 DEG C, by above-mentioned
Two kinds of solution are that 1:10～10:1 ratio mixes at least 20min in cordycepin and the mol ratio of sodium alginate, wash by centrifugation, surpass
Cordycepin nano controlled-release ball is obtained, by the CaCl of this cordycepin nano controlled-release ball Yu 0.125mol/L after sound dispersion2Solution equal-volume
After mixing cured, wash, obtain after drying the cordycepin nano controlled-release capsule powder of a diameter of 200nm～300nm by centrifugation.
Cordycepin nano controlled-release capsule the most according to claim 1, it is characterised in that described weakly acidic solution be through the past from
Water-reducible 1% formic acid of son, 1% acetic acid, 0.5% phosphoric acid, 1% citric acid or 0.5% boric acid.
Cordycepin nano controlled-release capsule the most according to claim 1, it is characterised in that described alkaline solution is 1%KOH solution
Or 1%NaOH solution.
4. the preparation method of a cordycepin nano controlled-release capsule, it is characterised in that comprise the steps:
(1) cordycepin is dissolved in weakly acidic solution, obtains the cordycepin solution that concentration is 100mol/L；
(2) sodium alginate is dissolved in alkaline solution, obtains the sodium alginate soln that concentration is 1mol/L；
(3) sodium alginate soln that cordycepin solution step (1) obtained and step (2) obtain is according to cordycepin and alginic acid
The mol ratio of sodium is that the ratio of 1:10～10:1 mixes at least 20min, by centrifugation, washing, obtains cordycepin after ultrasonic disperse and receives
Rice sustained-release microspheres；
(4) cordycepin nano controlled-release ball step (3) obtained and concentration are the CaCl of 0.125mol/L2Solution equal-volume mixes,
After solidification, by centrifugation, washing, obtain the cordycepin nano controlled-release capsule powder of a diameter of 200nm～300nm after drying.
The preparation method of a kind of cordycepin nano controlled-release capsule the most according to claim 4, it is characterised in that in step (1),
Described weakly acidic solution is through water-reducible 1% formic acid of deionization, 1% acetic acid, 0.5% phosphoric acid, 1% citric acid or 0.5%
Boric acid.
The preparation method of a kind of cordycepin nano controlled-release capsule the most according to claim 4, it is characterised in that in step (2),
Described alkaline solution is 1%KOH solution or 1%NaOH solution.
The preparation method of a kind of cordycepin nano controlled-release capsule the most according to claim 4, it is characterised in that in step (3),
Described cordycepin solution is 20 DEG C～40 DEG C with the mixing temperature of sodium alginate soln.
The preparation method of a kind of cordycepin nano controlled-release capsule the most according to claim 4, it is characterised in that in step (3),
According to rubbing of the sodium alginate contained in the cordycepin contained in 100mol/L cordycepin solution and 1mol/L sodium alginate soln
You mix than the ratio for 5:1.
The preparation method of a kind of cordycepin nano controlled-release capsule the most according to claim 4, it is characterised in that in step (3),
According to rubbing of the sodium alginate contained in the cordycepin contained in 100mol/L cordycepin solution and 1mol/L sodium alginate soln
You mix than the ratio for 10:1.
The preparation method of a kind of cordycepin nano controlled-release capsule the most according to claim 4, it is characterised in that step (4)
In, described cordycepin nano controlled-release ball and CaCl2Incorporation time 10min of solution～20min.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013093630A2 (en) * | 2011-12-22 | 2013-06-27 | Pronova Biopharma Norge As | Gelatin/alginate delayed release capsules comprising omega-3 fatty acids, and methods and uses thereof |
| CN103720659A (en) * | 2012-10-10 | 2014-04-16 | 五邑大学 | Preparation method of cordycepin controlled-release magnetic nanospheres |
| CN103622934A (en) * | 2013-11-13 | 2014-03-12 | 青海互丰农业科技集团有限公司 | Sustained-release cordycepin capsule and preparation method thereof |
Non-Patent Citations (1)
| Title |
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| 大黄酸肠溶性缓释微丸的研制;赵一洁;《万方数据库》;20140225;摘要第2-3段及正文第50页第1节 * |
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