CN105664168A - Preparation method and application of drug-loading nano silver particles - Google Patents
Preparation method and application of drug-loading nano silver particles Download PDFInfo
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Abstract
The invention discloses a preparation method and application of drug-loading nano silver particles.The preparation method includes the steps of A, preparing the aqueous solution of silver nitrate and a reducing drug solution; mixing 0.1-10mmol/L of the aqueous solution of silver nitrate with 10<-5>-10<-2>mol/L of the reducing drug solution to form a reaction solution; B, allowing the reaction solution to have reduction reaction for at least 0.5 hour under the temperature not lower than 20 DEG C, removing unreacted reducing drugs after the reaction, and drying to obtain the drug-loading nano silver particles.The invention further provides application of the prepared drug-loading nano silver particles to antitumor drugs and nano healthcare drugs.The preparation method has the advantages that the drug-loading nano silver particles can be prepared without extra adding of reducing agent, and the method is simple in preparation process, green, fast and simple; the drug-loading nano silver particles prepared by the method can release drugs in a sustained manner in a body and has targeted treating effect on cancer.
Description
Technical field
The present invention relates to pharmacy field, more specifically relate to the preparation method of a kind of medicament-carried nano silver particles, also relate to a kind of medicament-carried nano silver particles in the purposes prepared in Nano medication or nano-health care product simultaneously.
Background technology
Nano material refers to the material of range scale within the scope of 1-100nm, usually has the property being different from macro object or single atom, such as, and small-size effect, quantum effect, interfacial effect and macro quanta tunnel effect. In recent years, nano material is not only used widely in material field and electronic industry, also receives common concern in the research of biomedicine, medical diagnosis on disease and targeted therapy. Noble metal nano particles, particularly Nano silver grain, have that excellent antibacterial, antiviral property and specific surface are big, the surface easily character such as functionalization, shows good application prospect in drug controlled release field. Usually, not modified Nano silver grain often is difficult to reach good curative effect, and medicament-carried nano silver particles combines efficacy of drugs and Nano silver grain advantage effectively, has more advantage in disease treatment and medicament slow release.
In correlation technique, medicament-carried nano silver particles preparation method is first synthesis of nano silver particles, then carries out follow-up drug modification.
But it is found by the applicant that, need to add reductive agent or stablizer in this preparation process, such as the reagent such as sodium borohydride or DMF, these reagent contain certain toxicity, to nanometer poisonous follow-up biological applications being had a negative impact prepared.
Summary of the invention
It is an object of the invention to there are provided the preparation method of a kind of medicament-carried nano silver particles, adopt reductibility medicine as reductive agent, prepare medicament-carried nano silver particles. The method prepares medicament-carried nano silver particles not to be needed additionally to add reductive agent, and preparation process is simple, has green, fast and convenient advantage.
Another object of the present invention there are provided a kind of medicament-carried nano silver particles in the application prepared in Nano medication or nano-health care product, the medicament-carried nano silver particles of gained not only can realize the slow releasing of medicine in body, and cancer also has targeted therapy effect.
For solving above-mentioned technical problem, the present invention by the following technical solutions:
A preparation method for medicament-carried nano silver particles, its step is as follows:
A, preparation Silver Nitrate (AgNO3) the aqueous solution and reductibility drug solution; By Silver Nitrate (AgNO3) the aqueous solution (0.1 ~ 10mmol/L) and reductibility drug solution (10-5~10-2Mol/L) it is mixed to form reaction soln;
B, the reaction soln that steps A is obtained at a certain temperature (>=20 DEG C) carry out reduction reaction (>=0.5 hour), described reduction reaction removes unreacted reductibility medicine after terminating, obtain medicament-carried nano silver particles after dry.
As preferably, AgNO in described reaction soln3Concentration be 0.1 ~ 10mmol/L, the concentration of reductibility drug solution is greater than 10-5Mol/L, described reduction reaction time >=0.5 hour, described reduction reaction temperature >=20 DEG C.
As preferably, the described reductibility medicine in reductibility drug solution is the medicine being rich in phenolic hydroxyl group, is any mixture of a kind of in pidorubicin, NVP-XAA 723, flavonoid compound or flavonoid glycoside compound or two to four kinds.
As preferably, in described reaction soln, the concentration of reductibility medicine is 10-5~10-2mol/L。
As preferably, the described reduction reaction time is 0.5 ~ 72h, temperature of reaction is 50 ~ 180 DEG C.
The application of medicament-carried nano silver particles in preparation nanometer antitumor drug or nano-health care product, the steps include:
A, medicament-carried nano silver particles (0.5~50mg) is made tablet (routine techniques), or (0.5~50mg) isotonic saline solution injection liquid (routine techniques) of configuration medicine-carried nano particles, obtain final medicine;
B, tablet adopt oral way to take in, and injection liquid adopts intramuscular injection or intravenous injection mode to take in.
As preferably, the quality of medicament-carried nano silver particles in tablet or injection liquid is 0.5~50mg.
The present invention compared with prior art, has the following advantages and effect:
The medicament-carried nano silver particles of preparation can be used for nano target medicine or the exploitation of nano-health care product, it may be achieved to the targeted therapy of the multiple diseases such as cancer. This kind of novel, green, gentle, simple medicament-carried nano silver particles preparation method is significant, and has wide application and development prospect. Only need Ag+Source and reductibility medicine, reaction process does not add any poisonous organic reagent; Obtained load medicine Nano silver grain is not containing harmful reagent such as reductive agents, and preparation process green safety, does not cause disadvantageous effect to follow-up biomedical applications.
For the Nano silver grain that pidorubicin is coated, obtained nanoparticle contains Ag, C, O element, proves that the coated Nano silver grain of medicine is successfully prepared (see figure 2); Particle size range is 30-40nm, and the nanoparticle of this particle size range arrives cancerous tissue position (see figure 1) by passive target effect after being taken in by human body; The half-inhibition concentration of human liver cancer cell is (see figure 3) by this Nano silver grain, proves that it has potentiality in Therapeutic cancer.
Accompanying drawing explanation
Fig. 1 is the transmission electron microscope picture of a kind of pidorubicin coated with silver nanoparticle.
Fig. 2 is the EDX figure of a kind of pidorubicin coated with silver nanoparticle.
Fig. 3 is that a kind of pidorubicin coated with silver nanoparticle is to the suppression curve of human liver cancer cell (HpG2).
Embodiment
Nano material refers to the material of range scale within the scope of 1-100nm, usually has the property being different from macro object or single atom, such as, and small-size effect, quantum effect, interfacial effect and macro quanta tunnel effect.In recent years, nano material is not only used widely in material field and electronic industry, also receives common concern in the research of biomedicine, medical diagnosis on disease and targeted therapy. Noble metal nano particles, particularly Nano silver grain, have that excellent antibacterial, antiviral property and specific surface are big, the surface easily character such as functionalization, shows good application prospect in drug controlled release field. Usually, not modified Nano silver grain often is difficult to reach good curative effect, and medicament-carried nano silver particles combines efficacy of drugs and Nano silver grain advantage effectively, has more advantage in disease treatment and medicament slow release.
The preparation method of medicament-carried nano silver particles comprises " from top to bottom " and " from bottom to top " two class method. " from top to bottom " method requires first synthesis of nano silver particles, then carries out follow-up drug modification. The method step is many, operates loaded down with trivial details, and generated time is long. " from bottom to top " process that method grows at Nano silver grain can introduce medicine, simple to operate. But, the method reported at present usually needs to introduce chemical reducing agent and impels Ag+ to generate nano silver particles, this process often needs artificially add poisonous reductive agent or stablizer (reagent such as sodium borohydride, DMF), follow-up biological applications is had a negative impact. Therefore, a kind of novel, green, gentle, simple medicament-carried nano silver particles preparation method is significant in invention, and has wide application and development prospect.
Embodiment 1:
Below by specific embodiment and by reference to the accompanying drawings the present invention is described in further detail.
A preparation method for medicament-carried nano silver particles, its step is as follows:
A, preparation AgNO3The aqueous solution and reductibility drug solution; By AgNO3The aqueous solution (0.1 ~ 10mmol/L, 500ml) and reductibility drug solution (10-5~10-2Mol/L, 1ml) it is mixed to form reaction soln; Under certain temperature (>=20 DEG C), reaction soln is carried out reduction reaction, and described reduction reaction removes unreacted reductibility medicine after terminating, and obtains medicament-carried nano silver particles after dry.
B, preparation process only need add Ag+Source and reductibility medicine, be mixed with reaction soln, does not relate to any poisonous organic reagent in reduction reaction process; Obtained load medicine Nano silver grain is containing harmful reagent such as reductive agents, and preparation process green safety, does not cause disadvantageous impact to follow-up biomedical applications.
AgNO in C, described reaction soln3Concentration be 0.1 ~ 10mmol/L, the concentration of reductibility drug solution is greater than 10-5Mol/L, described reduction reaction time >=0.5 hour, described reduction reaction temperature >=20 DEG C. The time of described reduction reaction is shorter, and temperature of reaction is easy to control, and operation is simple.
Further, the reductibility medicine of described reductibility drug solution is the medicine being rich in phenolic hydroxyl group, is any mixture of a kind of in pidorubicin, NVP-XAA 723, flavonoid compound or flavonoid glycoside compound or two to four kinds. Described pidorubicin, NVP-XAA 723, flavonoid compound or flavonoid glycoside compound have certain reductibility, are the reductive agents of a kind of green; Redox reaction process is coated on nano grain of silver sub-surface as reductive agent, forms medicament-carried nano silver particles, it may be achieved to the targeted therapy of the multiple diseases such as cancer. Described cancer in particular is leukemia, mammary cancer, liver cancer, lung cancer, skin and mouth neoplasm etc.The purposes of described medicament-carried nano silver particles in preparation treatment leukemia, mammary cancer, liver cancer, lung cancer, skin and mouth neoplasm medicine.
Further, in described reaction soln, the concentration of reductibility medicine is 10-5~10-2mol/L。
Further, the described reduction reaction time is 0.5 or 1 or 3 or 5 or 8 or 15 or 20 or 2 or 32 or 38 or 46 or 54 or 61 or 67 or 72h, and temperature of reaction is 50 or 60 or 70 or 80 or 90 or 100 or 125 or 136 or 148 or 155 or 167 or 175 or 180 DEG C. The cycle short (>=0.5 hour) of reaction, temperature of reaction lower (temperature >=20 DEG C), the requirement of conversion unit is low, reduce the cost of reaction.
Adopt medicament-carried nano silver particles that above-mentioned preparation method obtains in the application prepared in Nano medication or nano-health care product.
Embodiment 2:
A preparation method for medicament-carried nano silver particles, comprises the following steps:
The AgNO of A, employing ultrapure water preparation 1mmol/L3The pidorubicin solution of solution and 20mmol/L;
B, by AgNO3Solution is heated to 120 DEG C, adds pidorubicin solution, AgNO in reaction soln after mixing3It is respectively 1mmol/L and 0.2mmol/L with the concentration of pidorubicin;
Described reaction soln is reacted 1h by C, continuation at 120 DEG C;
D, described reaction soln are cooled to room temperature (20-25 DEG C, identical below) after having reacted, adopt the dialysis membrane cleaning reaction solution of 300kDa, remove the pidorubicin not participating in reaction, namely obtain pidorubicin coated with silver nanoparticle after centrifugal drying.
With reference to accompanying drawing 1, the particle diameter of obtained Nano silver grain is at about 30-40nm, and the Surface coating of described Nano silver grain one layer of polymeric film, for pidorubicin becomes from combinate form. Show that the coated Nano silver grain of pidorubicin successfully synthesizes.
With reference to accompanying drawing 2, adopt electronic spectrum to be analyzed by the elementary composition of nanoparticle, can obviously observe the characteristic peak of Ag, C and O, show that pidorubicin medicament-carried nano silver particles is successfully synthesized.
With reference to accompanying drawing 3, HepG2 cell DMEM nutrient solution, to the experiment of human liver cancer cell HepG-2 restraining effect, for chart Zorubicin wraps up Nano silver grain to the impact of HepG-2 cell proliferation in vitro, is diluted to 1 × 10 by pidorubicin parcel Nano silver grain4Individual/ml, is inoculated in one piece of 96 orifice plate, 200 μ l/ holes. In 37 DEG C, 5%(volume fraction) CO2After cultivating 24h in incubator, the medicine-carried nano particles adding different concns makes it to required working fluid concentration range (0.1ug/ml 30ug/ml), after effect 48, removes nutrient solution, every hole adds 20 μ lMTT, and μ lDMSO dissolves to add 150 after 4h. Measure the optical density(OD) (OD) in each hole in microplate reader 490nm wavelength place, calculate cell inhibitory rate, inhibiting rate (%)=[(not medicine feeding hole OD value-medicine feeding hole OD value)/not medicine feeding hole OD value] × 100%. Adopt SPSS software Pro bit regression analysis calculation of half inhibitory concentration (IC50).
The half-inhibition concentration of medicine-carried nano particles described in accompanying drawing 3 is about 1.8 μ g/ml, shows that medicine-carried nano particles still has the effect of very strong inhibition tumor cell propagation at very low doses. Therefore the medicine-carried nano particles that prepared by the method can be used as novel nano targeted anticancer medicine preparation.
Embodiment 3:
A preparation method for medicament-carried nano silver particles, the steps include:
The AgNO of A, employing ultrapure water preparation 1mmol/L3The pidorubicin solution of solution and 100mmol/L;
B, by described AgNO3Solution is heated to 120 DEG C, adds described pidorubicin solution, AgNO in reaction soln after mixing3It is respectively 1mmol/L and 1mmol/L with the concentration of pidorubicin;
Described reaction soln is reacted 4h by C, continuation at 120 DEG C;
D, described reaction soln are cooled to room temperature after having reacted, and adopt the mode (more than three times) of eccentric cleaning to remove the pidorubicin not participating in reaction, namely obtain pidorubicin coated with silver nanoparticle after dry.
Embodiment 4:
A preparation method for medicament-carried nano silver particles, comprises the following steps:
The AgNO of A, employing ultrapure water preparation 1mmol/L3The pidorubicin solution of solution and 20mmol/L;
B, by described AgNO3Solution is heated to 140 DEG C, adds described pidorubicin solution, AgNO in reaction soln after mixing3It is respectively 1mmol/L and 0.2mmol/L with the concentration of pidorubicin;
Described reaction soln is reacted 1h by C, continuation at 140 DEG C;
D, described reaction soln are cooled to room temperature after having reacted, and adopt the dialysis membrane cleaning reaction solution of 300kDa, remove the pidorubicin not participating in reaction, namely obtain pidorubicin coated with silver nanoparticle after centrifugal drying.
Embodiment 5:
A preparation method for medicament-carried nano silver particles, comprises the following steps:
The AgNO of A, employing ultrapure water preparation 1mmol/L3The EGCG solution of solution and 2mmol/L;
B, by described AgNO3Solution is heated to 100 DEG C, adds described EGCG solution, AgNO in reaction soln after mixing3It is respectively 1mmol/L and 0.02mmol/L with the concentration of EGCG;
Described reaction soln is reacted 1h by C, continuation at 100 DEG C;
D, described reaction soln are cooled to room temperature after completing, and adopt the dialysis membrane cleaning reaction solution of 300kDa, remove the EGCG not participating in reaction, namely obtain EGCG coated with silver nanoparticle after centrifugal drying.
Embodiment 6:
A preparation method for medicament-carried nano silver particles, comprises the following steps:
The AgNO of A, employing ultrapure water preparation 1mmol/L3The EGCG solution of solution and 10mmol/L;
B, by described AgNO3Solution is heated to 100 DEG C, adds described EGCG solution, AgNO in reaction soln after mixing3It is respectively 1mmol/L and 0.1mmol/L with the concentration of EGCG;
Described reaction soln is reacted 1h by C, continuation at 120 DEG C;
D, described reaction soln are cooled to room temperature after completing, and adopt the dialysis membrane cleaning reaction solution of 300kDa, remove the EGCG not participating in reaction, namely obtain EGCG coated with silver nanoparticle after centrifugal drying.
Embodiment 7:
A preparation method for medicament-carried nano silver particles, comprises the following steps:
The AgNO of A, employing ultrapure water preparation 1mmol/L3The rutin solution of solution and 10mmol/L;
B, by described AgNO3Solution is heated to 100 DEG C, adds described rutin solution, and after mixing, in reaction soln, the concentration of AgNO3 and rutin is respectively 1mmol/L and 0.mmol/L;
Described reaction soln is reacted 1h by C, continuation at 120 DEG C;
D, described reaction soln are cooled to room temperature after completing, and adopt the dialysis membrane cleaning reaction solution of 300kDa, remove the rutin not participating in reaction, namely obtain rutin coated with silver nanoparticle after centrifugal drying.
Embodiment 8:
A preparation method for medicament-carried nano silver particles, comprises the following steps:
The AgNO of A, employing ultrapure water preparation 1mmol/L3The Quercetin solution of solution and 10mmol/L;
B, by described AgNO3Solution is heated to 100 DEG C, adds described Quercetin solution, AgNO in reaction soln after mixing3It is respectively 1mmol/L and 0.1mmol/L with the concentration of Quercetin;
C, described reaction soln is reacted 1h at 120 DEG C;
D, described reaction soln are cooled to room temperature after having reacted, and adopt the dialysis membrane cleaning reaction solution of 300kDa, remove the Quercetin not participating in reaction, namely obtain Quercetin coated with silver nanoparticle after centrifugal drying.
Embodiment 9:
The application of medicament-carried nano silver particles in nanometer antitumor drug, the steps include:
A, by nano silver particles coated for 10mg pidorubicin, dilute with 20ml isotonic saline solution and it is uniformly dispersed, obtain intravenous fluid;
B, by said medicine intravenous injection, every day or the next day once, a course for the treatment of 120mg altogether.
For pidorubicin, it provides the application of this medicament-carried nano silver particles in antitumor drug.
The application of described medicament-carried nano silver particles in preparation treatment leukemia, mammary cancer, liver cancer, lung cancer, skin and mouth neoplasm medicine.
Embodiment 10:
Medicament-carried nano silver particles, in the application prepared in nano-health care product, the steps include:
A, by nano silver particles coated for 8mg rutin, make tablet (routine techniques);
Within after B, supper 2 hours, taking, once a day, a course for the treatment of is total to 120mg.
Described healthcare products are soybean lecithin, kuh-seng pancreas cytokines, wheatgerm oil etc., have the effect reducing capillary permeability and fragility, keep and recover the normal elasticity of capillary vessel. Clinical in preventing and treating Intracerebral hemorrhage, hypertension, diabetes, retinal hemorrhage, purple scar and acute hemorrhagic ephritis.
Above embodiment only in order to the technical scheme of the present invention to be described, is not intended to limit; Although with reference to previous embodiment to invention has been detailed description, it will be understood by those within the art that: the technical scheme described in previous embodiment still can be modified by it, or wherein some or all of technology feature is carried out equivalent replacement; And these amendments or replacement, do not make the scope of the essence disengaging embodiment of the present invention technical scheme of appropriate technical solution.
Claims (3)
1. a preparation method for medicament-carried nano silver particles, the steps include:
The aqueous solution of A, preparation Silver Nitrate and reductibility drug solution; By the aqueous solution 0.1 ~ 10mmol/L of Silver Nitrate and reductibility drug solution 10-5~10-2Mol/L is mixed to form reaction soln;
B, the reaction soln at temperature >=20 DEG C that steps A obtains being carried out reduction reaction >=0.5 hour, described reduction reaction removes unreacted reductibility medicine after terminating, obtain medicament-carried nano silver particles after dry;
In described reaction soln, the concentration of Silver Nitrate is 0.1 ~ 10mmol/L, and the concentration of reductibility drug solution is greater than 10- 5Mol/L, described reduction reaction time >=0.5 hour, described reduction reaction temperature >=20 DEG C;
The described reductibility medicine in reductibility drug solution is the medicine being rich in phenolic hydroxyl group, is any mixture of a kind of in pidorubicin, NVP-XAA 723, flavonoid compound or flavonoid glycoside compound or two to four kinds;
In described reaction soln, the concentration of reductibility medicine is 10-5~10-2Mol/L;
The described reduction reaction time is 0.5 ~ 72h, and temperature of reaction is 50 ~ 180 DEG C.
2. a kind of medicament-carried nano silver particles according to claim 1 treats the application in tumour Nano medication in preparation;
Described tumour is leukemia, mammary cancer, liver cancer, lung cancer, skin and mouth neoplasm.
3. a kind of medicament-carried nano silver particles according to claim 1 is preparing application in nano-health care product;
Described healthcare products are soybean lecithin, kuh-seng pancreas cytokines, wheatgerm oil etc.
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CN107088661A (en) * | 2017-05-11 | 2017-08-25 | 扬州大学 | A kind of synthetic method of Nano Silver |
CN109877337A (en) * | 2019-03-14 | 2019-06-14 | 华中农业大学 | A kind of preparation method for the spherical gold nano grain that size is controllable |
CN110026563A (en) * | 2019-03-14 | 2019-07-19 | 华中农业大学 | A kind of preparation method for the flower-shaped gold nano grain that size is controllable |
CN110947028A (en) * | 2019-12-06 | 2020-04-03 | 通化师范学院 | Ag nano particles prepared from soybean leaching solution and preparation method of liquid adhesive bandage of Ag nano particles |
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CN107088661A (en) * | 2017-05-11 | 2017-08-25 | 扬州大学 | A kind of synthetic method of Nano Silver |
CN109877337A (en) * | 2019-03-14 | 2019-06-14 | 华中农业大学 | A kind of preparation method for the spherical gold nano grain that size is controllable |
CN110026563A (en) * | 2019-03-14 | 2019-07-19 | 华中农业大学 | A kind of preparation method for the flower-shaped gold nano grain that size is controllable |
CN110947028A (en) * | 2019-12-06 | 2020-04-03 | 通化师范学院 | Ag nano particles prepared from soybean leaching solution and preparation method of liquid adhesive bandage of Ag nano particles |
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