CN103690487A - Carrier-free micro-nano resveratrol medicament and preparation and application thereof - Google Patents
Carrier-free micro-nano resveratrol medicament and preparation and application thereof Download PDFInfo
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- CN103690487A CN103690487A CN201310691998.XA CN201310691998A CN103690487A CN 103690487 A CN103690487 A CN 103690487A CN 201310691998 A CN201310691998 A CN 201310691998A CN 103690487 A CN103690487 A CN 103690487A
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Abstract
The invention discloses a carrier-free micro-nano resveratrol medicament and preparation and application thereof. The carrier-free micro-nano resveratrol medicament is a product prepared by a preparation method comprising the following steps: (1) putting resveratrol powder into a crucible, and calcining in a tubular furnace in the presence of gas protection; (2) after calcining, cooling the tubular furnace to the normal temperature to obtain the micro-nano resveratrol medicament. The micro-nano resveratrol medicament has the advantages that (1) no carriers or organic solvents are contained, so that the medicament content is up to 100 percent; (2) the defects of low water solubility and low bioavailability are overcome, the product is needle-shaped or strip-shaped, the width is 0.2-0.5 mu m, and the solubility of the product in water is 30-50mumol/L; (3) the IC50 (50% inhibitory concentration) value of the product to a human hepatoma cell HeLa is 0.1-0.2 mu mol/mL, and the IC50 value to a human hepatoma cell HepG2 is 0.2-0.3 mu mol/mL.
Description
Technical field
The present invention relates to medical technical field, be specifically related to the micro-nano resveratrol medicine of a kind of carrier-free and preparation and application.
Background technology
Resveratrol chemistry Resveratrolk by name, be plant running into spontaneous antitoxin under unfavorable conditions, in 72 kind of plant such as Fructus Vitis viniferae, Rhizoma Polygoni Cuspidati and Semen arachidis hypogaeae, exist.Resveratrol has multiple pharmacologically active, as regulated lipoprotein metabolism, suppresses LDL oxidation, the generation of anticoagulant and minimizing prostaglandin etc.The most noticeable pharmaceutically active of resveratrol is its stronger antitumor action, kinds of tumors is had to very high inhibition active, become at present most potential natural antitumor medicine, people also find that this material has potential therapeutical effect to diabetes in recent years.Therefore resveratrol is with a wide range of applications in medicine, field of health care products, and market value is high.Although the pharmaceutically active of resveratrol has obtained widely approval, its hydrophobicity is strong, in water, dissolves hardly, cause in its body bioavailability low, has had a strong impact on its being widely used clinically.
When the size of medicine drops to micro-nano scope, owing to thering is less particle diameter and huge specific surface area, can increase dissolubility and the dissolution rate of insoluble medicine, also can increase contacting of medicine and gastrointestinal tract wall, thereby promote the absorption of medicine, improve the bioavailability of insoluble medicine.The micro-nano resveratrol medicine of having reported is at present considerably less, and these micro-nano medicines are all containing inert carrier.As Chinese patent CN101579291A has announced a kind of resveratrol phospholipid composite nano-emulsion, this nanometer resveratrol adopts phospholipid as carrier, and preparation process is added polyhydric alcohol; Chinese patent CN101317832A has announced a kind of oral resveratrol nanometer drug delivery system, and this system adopts Semen Tritici aestivi alcohol as carrier, and preparation process need be added organic solvent and surfactant (or stabilizing agent); Chinese patent CN103040754A has announced a kind of resveratrol nanometer liposome, and this system needs lipid film material to do carrier, and preparation process also needs to add organic solvent.In the above-mentioned micro-nano resveratrol of having announced, the membership that adds of inert carrier brings many unfavorable factors: 1. in Nano medication system, the quality of carrier, usually above medicine, has reduced the effective content of system Chinese medicine; 2. carrier has side effect or adverse effect conventionally: 3. the synthetic of carrier wasted time and energy.
Summary of the invention
Technical problem to be solved by this invention is to provide the micro-nano resveratrol medicine of a kind of carrier-free and preparation thereof for above-mentioned prior art, water solublity and the active anticancer of described resveratrol medicine obviously improve, and another object of the present invention is to provide the micro-nano resveratrol medicine of carrier-free in the application of preparing aspect antitumor product and health product.
The present invention solves the problems of the technologies described above adopted technical scheme: the micro-nano resveratrol medicine of a kind of carrier-free, its pattern is needle-like or band shape, and mean breadth is 0.2～0.5 μ m, and the dissolubility in water is 30～50 μ mol/L, it is following preparation method products therefrom, comprises the steps:
(1) resveratrol powder is placed in to crucible, under gas shield, in tube furnace, calcines;
(2) after calcining finishes, tube furnace temperature is down to room temperature, obtains the micro-nano resveratrol medicine of carrier-free.
Press such scheme, described protective gas is at least one in argon, helium, nitrogen and carbon dioxide.
Press such scheme, the flow velocity of described protective gas is 60～180sccm(mark condition ml/min).
Press such scheme, described calcining heat is 80～260 ℃.
Press such scheme, described calcination time is 30～200min.
The preparation method of the micro-nano resveratrol medicine of described carrier-free, comprises the steps:
(1) resveratrol powder is placed in to crucible, under gas shield, in tube furnace, calcines;
(2) after calcining finishes, tube furnace temperature is down to room temperature, obtains the micro-nano resveratrol medicine of carrier-free.
The micro-nano resveratrol medicine of described carrier-free is as the application of human cervical carcinoma's antitumor drug or people's hepatocarcinoma antitumor drug.
The micro-nano resveratrol medicine of carrier-free provided by the present invention has the following advantages:
1) containing carrier and organic solvent, medicament contg is up to 100%, the harmful effect of having avoided carrier to bring;
2) by the change of medicine pattern and size, thereby it is low to improve its water solublity, the defect that bioavailability is poor; Product pattern is needle-like or band shape, and width is 0.2～0.5 μ m; The dissolubility of product in water is 30～50 μ mol/L, is not calcine 4～7 times of resveratrol;
3) IC of product to human cervical carcinoma cell HeLa
50value (suppression ratio is 50% required drug level) is 0.1～0.2 μ mol/mL, the IC to human liver cancer cell HepG2
50value is 0.2～0.3 μ mol/mL, does not compare IC with calcining resveratrol
50value declines 40～50%.
Accompanying drawing explanation
Fig. 1 is the scanning electron microscope (SEM) photograph of resveratrol raw material;
Fig. 2 is the scanning electron microscope (SEM) photograph of the micro-nano resveratrol medicine of embodiment 1;
Fig. 3 is the scanning electron microscope (SEM) photograph of the micro-nano resveratrol medicine of embodiment 2;
Fig. 4 is the infared spectrum of the micro-nano resveratrol medicine of embodiment 3 and resveratrol raw material.
The specific embodiment
Further illustrate by the following examples the present invention, but the present invention is not limited to the content that the following example comprises.
The preparation method of micro-nano resveratrol medicine, comprises the steps:
By resveratrol material powder (purchased from Aladdin, purity is 99%) tiling is placed in crucible, crucible is placed in to quartz ampoule, adjusting nitrogen flow rate is 60sccm, temperature is 150 ℃, in tube furnace, calcine 30min, recovery sample when temperature is down to room temperature, can obtain micro-nano resveratrol medicine.
Accompanying drawing 2 is scanning electron microscope (SEM) photographs of the micro-nano resveratrol medicine of embodiment 1, and as we know from the figure, product pattern is banded, compare with raw material resveratrol, and pattern homogeneous, width reduces, and mean breadth is 0.5 μ m.
Embodiment 2
The preparation method of micro-nano resveratrol medicine, comprises the steps:
The tiling of resveratrol material powder is placed in crucible, crucible is placed in to quartz ampoule, adjusting nitrogen flow rate is 120sccm, and temperature is 180 ℃, calcines 60min in tube furnace, and recovery sample when temperature is down to room temperature can obtain micro-nano resveratrol medicine.
Accompanying drawing 3 is scanning electron microscope (SEM) photographs of the micro-nano resveratrol medicine of embodiment 2, and as we know from the figure, product pattern is needle-like or band shape, compares with raw material, and size obviously reduces, and mean breadth is 0.3 μ m.
Embodiment 3
The preparation method of micro-nano resveratrol medicine, comprises the steps:
The tiling of resveratrol material powder is placed in crucible, crucible is placed in to quartz ampoule, adjusting nitrogen flow rate is 120sccm, temperature is 180 ℃, in tube furnace, calcine 90min, recovery sample when temperature is down to room temperature, can obtain micro-nano resveratrol medicine.
The infrared spectrum contrast of micro-nano resveratrol and resveratrol raw material
The micro-nano resveratrol of embodiment 3 and the infrared spectrum of resveratrol raw material, adopt Thermo Nicolet520 determination of infrared spectroscopy, sees accompanying drawing 4.Micro-nano resveratrol after calcining is compared with raw material resveratrol as seen from the figure, and significant change does not occur spectrogram, shows that calcination process does not destroy pharmaceutical chemistry structure.
Embodiment 4
The preparation method of micro-nano resveratrol medicine, comprises the steps:
The tiling of resveratrol material powder is placed in crucible, crucible is placed in to quartz ampoule, regulating argon flow velocity is 180sccm, temperature is 215 ℃, in tube furnace, calcine 30min, recovery sample when temperature is down to room temperature, can obtain micro-nano resveratrol medicine.
The external water solublity contrast of micro-nano resveratrol and resveratrol raw material
Micro-nano resveratrol prepared by embodiment 1～4 method and resveratrol raw material stir 48 hours in water, with the membrane filtration of 0.45 μ m, remove undissolved solid, adopt Shimadzu UV-2550 UV, visible light luminosity instrumentation to determine the content of resveratrol in solution, the results are shown in Table 1.The micro-nano resveratrol dissolubility that resveratrol raw material obtains after calcining is as seen from table significantly improved.
Micro-nano resveratrol and the contrast of resveratrol raw material anticancer experiment in vitro
Test sample: the micro-nano resveratrol of preparing according to embodiment 1 and 2 methods
Method: select human cervical carcinoma cell HeLa as subject cell strain, the application micro-nano resveratrol of variable concentrations and resveratrol raw material act on cell 48 hours, adopt mtt assay to observe the inhibition of medicine to growth of tumour cell, experiment in triplicate, result adopts the required micro-nano resveratrol concentration of inhibition 50% Growth of Cells to represent, i.e. IC
50value, in Table 2.
The IC of the micro-nano resveratrol of table 2 to HeLa cell
50value
Micro-nano resveratrol is significantly higher than resveratrol raw material to the growth inhibited effect of HeLa cell as seen from table, suppressing the required micro-nano resveratrol concentration of 50% Growth of Cells is 0.11～0.14 μ mol/mL, and required resveratrol material concentration is 0.24 μ mol/mL.
Micro-nano resveratrol and the contrast of resveratrol raw material anticancer experiment in vitro
Test sample: the micro-nano resveratrol of preparing according to embodiment 1 and 2 methods
Method: select human liver cancer cell HepG2 as subject cell strain, the application micro-nano resveratrol of variable concentrations and resveratrol act on cell 48 hours, adopt mtt assay to observe the inhibition of medicine to growth of tumour cell, experiment in triplicate, result adopts the required micro-nano resveratrol concentration of inhibition 50% Growth of Cells to represent, i.e. IC
50value, the results are shown in Table 3.
The IC of the micro-nano resveratrol of table 3 to HepG2 cell
50value
Micro-nano resveratrol is significantly higher than resveratrol raw material to the growth inhibited effect of HepG2 cell as seen from table, suppressing the required micro-nano resveratrol concentration of 50% Growth of Cells is 0.20～0.24 μ mol/mL, and required resveratrol material concentration is 0.43 μ mol/mL.
Conclusion: micro-nano resveratrol is compared with resveratrol raw material, size decreases, chemical constitution does not change, and water solublity increases, and to the inhibition of tumor cell is active, obviously strengthens.
Claims (13)
1. the micro-nano resveratrol medicine of carrier-free, its pattern is needle-like or band shape, and mean breadth is 0.2～0.5 μ m, and the dissolubility in water is 30～50 μ mol/L, and it is following preparation method products therefrom, comprises the steps:
(1) resveratrol powder is placed in to crucible, under gas shield, in tube furnace, calcines;
(2) after calcining finishes, tube furnace temperature is down to room temperature, obtains the micro-nano resveratrol medicine of carrier-free.
2. the micro-nano resveratrol medicine of carrier-free according to claim 1, is characterized in that described protective gas is at least one in argon, helium, nitrogen and carbon dioxide.
3. the micro-nano resveratrol medicine of carrier-free according to claim 2, the flow velocity that it is characterized in that described protective gas is 60～180sccm(mark condition ml/min).
4. according to the micro-nano resveratrol medicine of carrier-free described in claim 1 or 2 or 3, it is characterized in that described calcining heat is 80～260 ℃.
5. the micro-nano resveratrol medicine of carrier-free according to claim 4, is characterized in that described calcination time is 30～200min.
6. the preparation method of the micro-nano resveratrol medicine of carrier-free claimed in claim 1, comprises the steps:
(1) resveratrol powder is placed in to crucible, under gas shield, in tube furnace, calcines;
(2) after calcining finishes, tube furnace temperature is down to room temperature, obtains the micro-nano resveratrol medicine of carrier-free.
7. the preparation method of the micro-nano resveratrol medicine of carrier-free according to claim 6, is characterized in that described protective gas is at least one in argon, helium, nitrogen and carbon dioxide.
8. the preparation method of the micro-nano resveratrol medicine of carrier-free according to claim 7, the flow velocity that it is characterized in that described protective gas is 60～180sccm(mark condition ml/min).
9. according to the preparation method of the micro-nano resveratrol medicine of carrier-free described in claim 6 or 7 or 8, it is characterized in that described calcining heat is 80～260 ℃.
10. the preparation method of the micro-nano resveratrol medicine of carrier-free according to claim 9, is characterized in that described calcining heat is 150～215 ℃.
The preparation method of the micro-nano resveratrol medicine of 11. carrier-free according to claim 9, is characterized in that described calcination time is 30～200min.
The preparation method of the micro-nano resveratrol medicine of 12. carrier-free according to claim 11, is characterized in that described calcination time is 30～90min.
The micro-nano resveratrol medicine of 13. carrier-free claimed in claim 1 is as the application of human cervical carcinoma's antitumor drug or people's hepatocarcinoma antitumor drug.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102106816A (en) * | 2010-12-16 | 2011-06-29 | 天津迈迪瑞康生物医药科技有限公司 | Resveratrol nanometer preparation and preparation method thereof |
| US20120121699A1 (en) * | 2009-05-14 | 2012-05-17 | Hsiehs Biotech (Singapore) Pte Ltd | Lycopene and resveratrol dietary supplement |
| CN103142457A (en) * | 2013-01-17 | 2013-06-12 | 西安电子科技大学 | Resveratrol nanometer-preparation preparation method |
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- 2013-12-17 CN CN201310691998.XA patent/CN103690487B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120121699A1 (en) * | 2009-05-14 | 2012-05-17 | Hsiehs Biotech (Singapore) Pte Ltd | Lycopene and resveratrol dietary supplement |
| CN102106816A (en) * | 2010-12-16 | 2011-06-29 | 天津迈迪瑞康生物医药科技有限公司 | Resveratrol nanometer preparation and preparation method thereof |
| CN103142457A (en) * | 2013-01-17 | 2013-06-12 | 西安电子科技大学 | Resveratrol nanometer-preparation preparation method |
Non-Patent Citations (2)
| Title |
|---|
| 陈正爱等: "白藜芦醇抗胃癌作用机制的研究进展", 《延边大学医学学报》 * |
| 高欣等: "纳米级白藜芦醇和白藜芦醇β-环糊精包合物生物利用度的比较研究", 《中草药》 * |
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