CN103690487B - 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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- CN103690487B CN103690487B CN201310691998.XA CN201310691998A CN103690487B CN 103690487 B CN103690487 B CN 103690487B CN 201310691998 A CN201310691998 A CN 201310691998A CN 103690487 B CN103690487 B CN 103690487B
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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 art, be specifically related to a kind of carrier-free micro-nano resveratrol medicament and Synthesis and applications thereof.
Background technology
Resveratrol chemistry Resveratrolk by name, be plant running into spontaneous antitoxin under unfavorable conditions, exist in 72 kind of plant such as Fructus Vitis viniferae, Rhizoma Polygoni Cuspidati and Semen arachidis hypogaeae.Resveratrol has multiple pharmacologically active, as regulated lipoprotein metabolism, suppresses LDL oxidation, the generation etc. of anticoagulant and minimizing prostaglandin.The most noticeable pharmaceutically active of resveratrol is its stronger antitumor action, to kinds of tumors, there is very high inhibit activities, become most potential natural antitumor medicine at present, 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 obtains admit widely, its hydrophobicity is strong, dissolves hardly, cause bioavailability in its body low in water, has had a strong impact on its widely using clinically.
When the size of medicine drops to micro-nano scope, owing to having less particle diameter and huge specific surface area, dissolubility and the dissolution rate of insoluble medicine can be increased, also can increase the contact of medicine and gastrointestinal tract wall, thus promote the absorption of medicine, improve the bioavailability of insoluble medicine.The micro-nano resveratrol medicament reported at present is considerably less, and these micro-nano medicines are all containing inert carrier.As Chinese patent CN101579291A discloses a kind of resveratrol phospholipid composite nano-emulsion, this nanometer resveratrol adopts phospholipid as carrier, and preparation process adds polyhydric alcohol; Chinese patent CN101317832A discloses a kind of oral resveratrol nanometer drug delivery system, and this system adopts Semen Tritici aestivi alcohol as carrier, and preparation process need add organic solvent and surfactant (or stabilizing agent); Chinese patent CN103040754A discloses a kind of resveratrol nano-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 announced, the membership that adds of inert carrier brings many unfavorable factors: 1. in Nano medication system, the quality of carrier, usually above medicine, reduces the effective content of system Chinese medicine; 2. carrier has side effect or adverse effect usually: 3. the synthesis of carrier is wasted time and energy.
Summary of the invention
Technical problem to be solved by this invention provides a kind of carrier-free micro-nano resveratrol medicament and preparation thereof for above-mentioned prior art, water solublity and the active anticancer of described resveratrol medicament significantly improve, and another object of the present invention is to provide carrier-free micro-nano resveratrol medicament and is preparing the application in antitumor product and health product.
The present invention solves the problems of the technologies described above adopted technical scheme: a kind of carrier-free micro-nano resveratrol medicament, its pattern is needle-like or band shape, and mean breadth is 0.2 ~ 0.5 μm, and the dissolubility in water is 30 ~ 50 μm of ol/L, it is following preparation method products therefrom, comprises the steps:
(1) resveratrol powder is placed in crucible, calcines in tube furnace under gas shield;
(2), after calcining terminates, tube furnace temperature is down to room temperature, obtains carrier-free micro-nano resveratrol medicament.
By such scheme, described protective gas is at least one in argon, helium, nitrogen and carbon dioxide.
By such scheme, the flow velocity of described protective gas is that 60 ~ 180sccm(marks condition ml/min).
By such scheme, described calcining heat is 80 ~ 260 DEG C.
By such scheme, described calcination time is 30 ~ 200min.
The preparation method of described carrier-free micro-nano resveratrol medicament, comprises the steps:
(1) resveratrol powder is placed in crucible, calcines in tube furnace under gas shield;
(2), after calcining terminates, tube furnace temperature is down to room temperature, obtains carrier-free micro-nano resveratrol medicament.
Described carrier-free micro-nano resveratrol medicament is as the application of human cervical carcinoma's antitumor drug or people's hepatocarcinoma antitumor drug.
Carrier-free micro-nano resveratrol medicament provided by the present invention has the following advantages:
1) not containing carrier and organic solvent, medicament contg, up to 100%, avoids the harmful effect that carrier brings;
2) by the change of medicine pattern and size, thus it is low to improve its water solublity, the defect of bioavailability difference; Product pattern is needle-like or band shape, and width is 0.2 ~ 0.5 μm; The dissolubility of product in water is 30 ~ 50 μm of ol/L, is 4 ~ 7 times that do not calcine resveratrol;
3) product is to the IC of human cervical carcinoma cell HeLa
50value (drug level of suppression ratio needed for 50%) is 0.1 ~ 0.2 μm of ol/mL, to the IC of human liver cancer cell HepG2
50value is 0.2 ~ 0.3 μm of ol/mL, and does not calcine compared with resveratrol, IC
50value decline 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 embodiment 1 micro-nano resveratrol medicament;
Fig. 3 is the scanning electron microscope (SEM) photograph of embodiment 2 micro-nano resveratrol medicament;
Fig. 4 is the infared spectrum of embodiment 3 micro-nano resveratrol medicament and resveratrol raw material.
Detailed description of the invention
Further illustrate the present invention by the following examples, but the present invention is not limited to the content that the following example comprises.
Embodiment 1
The preparation method of micro-nano resveratrol medicament, comprises the steps:
By resveratrol material powder (purchased from Aladdin, purity is 99%) tiling is placed in crucible, crucible is placed in quartz ampoule, adjustment nitrogen flow rate is 60sccm, temperature is 150 DEG C, in tube furnace, calcine 30min, recovery sample when temperature is down to room temperature, can micro-nano resveratrol medicament be obtained.
Accompanying drawing 1 is the scanning electron microscope (SEM) photograph of the resveratrol material powder adopting the shooting of Hitachi S4800 type scanning electron microscope, and as can be seen from the figure raw material pattern is in block or rod shape, and in a jumble, size is comparatively large, and Breadth Maximum is more than 2 μm.
Accompanying drawing 2 is scanning electron microscope (SEM) photographs of embodiment 1 micro-nano resveratrol medicament, and as we know from the figure, product pattern is banded, and compared with raw material resveratrol, pattern is homogeneous, and width reduces, and mean breadth is 0.5 μm.
Embodiment 2
The preparation method of micro-nano resveratrol medicament, comprises the steps:
Be placed in crucible by the tiling of resveratrol material powder, crucible is placed in quartz ampoule, and adjustment nitrogen flow rate is 120sccm, and temperature is 180 DEG C, in tube furnace, calcine 60min, and recovery sample when temperature is down to room temperature can obtain micro-nano resveratrol medicament.
Accompanying drawing 3 is scanning electron microscope (SEM) photographs of embodiment 2 micro-nano resveratrol medicament, and as we know from the figure, product pattern is needle-like or band shape, and compared with raw material, size obviously reduces, and mean breadth is 0.3 μm.
Embodiment 3
The preparation method of micro-nano resveratrol medicament, comprises the steps:
Be placed in crucible by the tiling of resveratrol material powder, crucible is placed in quartz ampoule, and adjustment nitrogen flow rate is 120sccm, temperature is 180 DEG C, in tube furnace, carry out calcining 90min, recovery sample when temperature is down to room temperature, can micro-nano resveratrol medicament be obtained.
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, see accompanying drawing 4.Micro-nano resveratrol as seen from the figure after calcining is compared with raw material resveratrol, and spectrogram significant change does not occur, and shows that calcination process does not destroy pharmaceutical chemistry structure.
Embodiment 4
The preparation method of micro-nano resveratrol medicament, comprises the steps:
The tiling of resveratrol material powder is placed in crucible, crucible is placed in quartz ampoule, regulate argon flow velocity to be 180sccm, temperature is 215 DEG C, in tube furnace, carry out calcining 30min, recovery sample when temperature is down to room temperature, can micro-nano resveratrol medicament be obtained.
Micro-nano resveratrol and the external water solublity contrast of resveratrol raw material
The micro-nano resveratrol prepare embodiment 1 ~ 4 method and resveratrol raw material stir 48 hours in water, undissolved solid is removed with the membrane filtration of 0.45 μm, adopt the measurement of Shimadzu UV-2550 UV, visible light luminosity 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 prepared according to embodiment 1 and 2 method
Method: select human cervical carcinoma cell HeLa as subject cell strain, application variable concentrations micro-nano resveratrol and resveratrol raw material act on cell 48 hours, mtt assay is adopted to observe the suppression of drug on tumor Growth of Cells, experiment in triplicate, result adopts the micro-nano resveratrol concentration needed for suppression 50% Growth of Cells to represent, i.e. IC
50value, in table 2.
Table 2 micro-nano resveratrol is to the IC of HeLa cell
50value
The growth inhibited effect of micro-nano resveratrol to HeLa cell is significantly higher than resveratrol raw material as seen from table, suppress the micro-nano resveratrol concentration needed for 50% Growth of Cells to be 0.11 ~ 0.14 μm of ol/mL, and required resveratrol material concentration is 0.24 μm of ol/mL.
Micro-nano resveratrol and the contrast of resveratrol raw material anticancer experiment in vitro
Test sample: the micro-nano resveratrol prepared according to embodiment 1 and 2 method
Method: select human liver cancer cell HepG2 as subject cell strain, application variable concentrations micro-nano resveratrol and resveratrol act on cell 48 hours, mtt assay is adopted to observe the suppression of drug on tumor Growth of Cells, experiment in triplicate, result adopts the micro-nano resveratrol concentration needed for suppression 50% Growth of Cells to represent, i.e. IC
50value, the results are shown in Table 3.
Table 3 micro-nano resveratrol is to the IC of HepG2 cell
50value
The growth inhibited effect of micro-nano resveratrol to HepG2 cell is significantly higher than resveratrol raw material as seen from table, suppress the micro-nano resveratrol concentration needed for 50% Growth of Cells to be 0.20 ~ 0.24 μm of ol/mL, and required resveratrol material concentration is 0.43 μm of ol/mL.
Conclusion: micro-nano resveratrol is compared with resveratrol raw material, and size diminishes, and chemical constitution does not change, water solublity increases, and obviously strengthens the inhibit activities of tumor cell.
Claims (4)
1. a carrier-free micro-nano resveratrol medicament, its pattern is needle-like or band shape, and mean breadth is 0.2 ~ 0.5 μm, and the dissolubility in water is 30 ~ 50 μm of ol/L, and it is following preparation method products therefrom, comprises the steps:
(1) resveratrol powder is placed in crucible, calcines in tube furnace under gas shield;
(2), after calcining terminates, tube furnace temperature is down to room temperature, obtains carrier-free micro-nano resveratrol medicament;
Described protective gas is at least one in argon, helium, nitrogen and carbon dioxide; The flow velocity of described protective gas is 60 ~ 180sccm (mark condition ml/min); Described calcining heat is 80 ~ 260 DEG C; Described calcination time is 30 ~ 200min.
2. the preparation method of carrier-free micro-nano resveratrol medicament according to claim 1, comprises the steps:
(1) resveratrol powder is placed in crucible, calcines in tube furnace under gas shield;
(2), after calcining terminates, tube furnace temperature is down to room temperature, obtains carrier-free micro-nano resveratrol medicament;
Described protective gas is at least one in argon, helium, nitrogen and carbon dioxide; The flow velocity of described protective gas is 60 ~ 180sccm (mark condition ml/min); Described calcining heat is 80 ~ 260 DEG C; Described calcination time is 30 ~ 200min.
3. the preparation method of carrier-free micro-nano resveratrol medicament according to claim 2, is characterized in that described calcining heat is 150 ~ 215 DEG C.
4. the preparation method of carrier-free micro-nano resveratrol medicament according to claim 2, is characterized in that described calcination time is 30 ~ 90min.
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| CN201310691998.XA CN103690487B (en) | 2013-12-17 | 2013-12-17 | Carrier-free micro-nano resveratrol medicament and preparation and application thereof |
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| CN103690487B true CN103690487B (en) | 2015-05-20 |
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| SG166688A1 (en) * | 2009-05-14 | 2010-12-29 | 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 |
| CN103142457B (en) * | 2013-01-17 | 2015-01-21 | 西安电子科技大学 | Resveratrol nanometer-preparation preparation method |
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