CN102772809B - Preparation method of nano magnetic control agglomeration chemotherapeutic pharmaceutical composition - Google Patents
Preparation method of nano magnetic control agglomeration chemotherapeutic pharmaceutical composition Download PDFInfo
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- CN102772809B CN102772809B CN 201210161667 CN201210161667A CN102772809B CN 102772809 B CN102772809 B CN 102772809B CN 201210161667 CN201210161667 CN 201210161667 CN 201210161667 A CN201210161667 A CN 201210161667A CN 102772809 B CN102772809 B CN 102772809B
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Abstract
The invention relates to a nano magnetic control agglomeration chemotherapeutic pharmaceutical composition which is characterized in that the molecular formula of the nano magnetic control agglomeration chemotherapeutic pharmaceutical composition is MM'xOH2+3x-n(sigma)A(sigma), wherein x=0.25-4; sigma is within the range from 0 to 0.1 and is larger than 0; M is one or two of divalent metal ions such as Zn<2+>, Mg<2+> and Fe<2+>; M' is one or two of trivalent metal ions such as Al<3+> and Fe<3+>; M and M' can not be iron ion at the same time; the molar ratio of M to M' is 1:4 to 4:1; A is I<125>, I<131> or P<32>; n=1 when A is I<->; n=2 when A is P; and the precursor of P<32> is 32PO4<3->, HP<32>O4<2-> or H2P<32>O4<->. The preparation method of the pharmaceutical composition comprises the steps of: reacting magnetic cations (Fe<2+> and Fe<3+>), radioactive anions (I<125>, I<131> or P<32>) and alkali compound, depositing, and aging to obtain the nano magnetic control agglomeration chemotherapeutic pharmaceutical composition. Under the combined action of the magnetic field and the ultrasonic wave, the composition can be agglomerated along a blood vessel, so that the embolism can not be formed.
Description
Technical field
The present invention relates to a kind of radioactivity chemotherapy pharmaceutical composition and preparation method thereof, the nano-drug preparation that especially can magnetic control gathers.
Background technology
At present, radiopharmaceutical NaI
131, NaI
129, NaH
2P
32O
4/ Na
2HP
32O
4, adjacent iodine
131Hippuric acid phosphorus iodine etc. is usually used in chemical examination and the treatment of cancers such as thyroid carcinoma, nephropathy inspection, often uses with the form of oral or injection.But because radiopharmaceutic side effect is stronger, medicine internal radiation meeting is when killing cancerous cell, because drug diffusion causes the infringement of healthy cell.
Can concentrate on around the focus by medicine and magnetic control gathers Nano medication, the healthy cell that can avoid the long range diffusion of medicine to cause is impaired.Thereby the compound Nano medication of magnetic nanoparticle is studied in the ascendant.But nano materials such as magnetic oxide commonly used at present are not high to the absorption property of medicine, and the formation thromboembolism of reuniting in narrow blood vessel easily, thereby greatly reduce the clinical practice of this class material.
Summary of the invention
In order to overcome the shortcoming of traditional magnetic control Nano medication, the object of the present invention is to provide a kind of nano magnetic to gather chemotherapy medicine composition, particle diameter is at 20-60nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 3～5AM
2/ Kg can be collected at affected area, and can not form thromboembolism under magnetic field and hyperacoustic combined effect.
Another object of the present invention is to provide a kind of nano magnetic to gather the preparation method of chemotherapy medicine composition, and technology is simple.
The technical solution adopted for the present invention to solve the technical problems is as follows:
Nano magnetic gathers chemotherapy medicine composition, it is characterized in that molecular formula is MM'
xOH
2+3x -n σA
σ, x=0.25-4 wherein, σ=in the 0-0.1 scope and greater than 0, M=Zn
2+, Mg
2+, Fe
2+Any bivalent metal ion or the mixture of any two kinds of bivalent metal ions; M'=Al
3+, Fe
3+Any trivalent metal ion or the mixture of any two kinds of trivalent metal ions; M and M ' are not iron ion simultaneously; The mol ratio of M and M' between 1:4 and 4:1, A=I
125,, I
131Perhaps P
32, and A=
125I
-, A=
131I
-The time n=1; A=P
32The time n=2; P wherein
32Precursor be
32PO
3- 4, HP
32O
2- 4Or H
2P
32O
- 4, A=HP preferably
32O
4 2-, because alkalescence helps to keep the layer structure of double-hydroxide (because reaction back solution is alkalescence, H
2P
32O
-Can be transformed into
32PO
3- 4, HP
32O
2- 4So, in example, only enumerated H
2P
32O
-Situation).
Wherein, the number of ions of magnetic cation is: Fe
2+=0-1.0; Fe
3+=0-1.0, and be not zero simultaneously.And the mol ratio of magnetic cation and radioactivity anion is 100～100000; With OH
-Meter, the mol ratio of alkali compounds and metal cation is 1～2, described metal cation is except the cationic bivalence of magnetic metal, trivalent metal ion.
Nano magnetic gathers the preparation method of chemotherapy medicine composition, it is characterized in that: in the mixed solution that contains magnetic cation, metal cation and radioactivity anion, add alkali compounds, in 40-120 ℃ of reaction 10-20 hour, precipitation, aging, obtain the anion intercalated nano magnetic of radioactivity and gather chemotherapy medicine composition; The metal cation that adopts is Mg
2+, Al
3+The time, reaction can be carried out in air, when the metal cation that adopts is Zn
2+The time, reaction is preferably carried out in nitrogen atmosphere, prevents the Zn in carbon dioxide in air and the solution
2+Reaction generates zinc carbonate.
Perhaps in the solution that contains magnetic cation, metal cation, add alkali compounds, 70-120 ℃ was reacted 12-48 hour, precipitation, aging, formation contains brucite, pass through then and radioactivity anionic ion exchange reaction, obtain the anion intercalated nano magnetic of radioactivity and gather chemotherapy medicine composition.
Described magnetic cation is Fe
2+, Fe
3+Arbitrary, its precursor is the arbitrary of solubility nitrate, chloride, sulfate; Described metal cation is Mg
2+, Zn
2+, Al
3+Arbitrary or both mixture, be combined with magnetic cation, constitute the double-hydroxide laminate jointly.Described alkali compounds is the arbitrary or mixture of carbonate, hydroxide, ammonia; Particularly be sodium carbonate, sodium hydroxide and ammonia.
The present invention inserts between the laminate of brucite the radioactivity anion because the laminate of the brucite that forms is positively charged, and the radioactivity anion is electronegative, combines by stronger static between the two.The hydrotalcite nano magnetic ion that forms can be mobile in blood vessel under high-intensity magnetic field, thereby be collected in lesions position.And be with general nanoparticle difference, the layer structure of the uniqueness of brucite makes that the active force between its laminate is not strong, thereby be subjected to external force such as ultrasound wave and do the time spent, laminate can be peeled off becomes littler ion, the rippability of brucite laminate can guarantee that the hydrotalcite nano granule can be under magnetic field and hyperacoustic combined effect, can not form thromboembolism, reach the controlled purpose of gathering.
The test of pesticide effectiveness:
Test group arranges: getting 50 of normal rat (male or female, body weight 220～280 grams), be divided into 5 groups, is respectively one group of matched group, and four groups of experimental grouies, administering mode are the hypogastric region subcutaneous injections; Wherein matched group administration 1ml contains 2 micromole NaI
131Aqueous solution, experimental group gives following sample, and effective dose of each sample and equating of matched group, namely is equivalent to 2mmolI
131/ ml;
Experimental group administration situation is as follows:
Contain I
131The aqueous solution 1ml of 1mg/Ld of Mg-FeLDH;
Contain I
131The aqueous solution 1ml of Zn-FeLDH1mg/Ld;
Contain I
131The aqueous solution 1ml of 1mg/Ld of Mg-Fe-AlLDH;
Contain I
131The aqueous solution 1ml of 1mg/Ld of Zn-Fe-AlLDH.
Animal is handled: the injection site of each group rat is added the magnetic field that magnetic field intensity is 2000T, and the injection site was disperseed with ultrasonic probe every 1 hour.After 8 days, determine the method for radioactive element concentration by measuring intensity of radiation, I in the blood of position under measurement injection site, extremity, the neck
131Concentration.Each position I of matched group
131Concentration is the 0.02%-0.04% of initial concentration; Experimental group rat injection site isotopic ion concentration is apparently higher than other positions, the 0.08%-0.12% that is about initial concentration, and the isotopic ion concentration at other positions also significantly reduces than matched group concentration, the 0.01%-0.02% that is about initial concentration illustrates that there is the effect of gathering preferably in magnetic field to this pharmaceutical composition.
Experiment began after 48 hours, the white mouse no abnormality seen, and blood drawing does not detect thrombosis; Proceed to test 48 hours, experiment condition is to apply magnetic field but not ultrasonic, do not see that white mouse is unusual, but blood has micro-thrombosis.This explanation ultrasonicly truly has certain aid dispersion effect for this medicine.
Description of drawings
The nano magnetic that Fig. 1 obtains for the embodiment of the invention 2 transports the Electronic Speculum figure of chemotherapy medicine composition.
The specific embodiment
Embodiment 1
Nano magnetic gathers chemotherapy medicine composition and contains I
131Being prepared as follows of Mg-FeLDH:
(1) mol ratio according to 2:1 takes by weighing ferric nitrate, magnesium nitrate, after the mixing, is dissolved in 100 ml waters, forms the mixed solution of ferric nitrate and magnesium nitrate, and is standby; (2) get NaOH2.0 gram, Na
2CO
38.5 gram is dissolved in 200 ml waters, forms NaOH and Na
2CO
3Mixed solution, standby;
(3) under vigorous stirring, the nitrate mixed solution that step (1) is formed is quickly poured in the alkali liquor of step (2) formation, stirs 12 hours down in 80 ℃; Precipitation is after filtration, washing back is dry, obtains MgFe(III) brucite;
(4) get 10 gram brucites, ultrasonic, be scattered in 200 ml waters, add 100 milligrams of NaI
131(Shanghai reagent company of traditional Chinese medicines group) is warming up to 40-120 ℃, under the stirring condition, ion exchange 10-20 hour, with sedimentation and filtration, washing, obtains nano hydrotalcite NaI after the drying
131Preparation.Particle diameter is 30-50nm, and the magnetic coercive force Hc value of sample is 0kA/m, specific saturation magnetization б
xBe 3.73AM
2/ Kg.
Embodiment 2
Nano magnetic gathers chemotherapy medicine composition and contains I
131Being prepared as follows of Zn-FeLDH:
(1) zinc nitrate, ferric nitrate are dissolved in 100 ml waters according to the mixed in molar ratio of 1:2, add 200 milligrams of NaI
131, stir, standby;
(2) get the NaOH3.2 gram and be dissolved in 200 ml waters, form NaOH solution, standby;
(3) under the vigorous stirring; the mixed solution that step (1) is formed is quickly poured into the NaOH solution that middle step (2) forms; under 60 ℃, nitrogen protection (secluding air), ageing 20 hours, product is after filtration, obtain nano hydrotalcite NaI after the washing, drying
131Preparation.Particle diameter is 30-50nm, and the magnetic coercive force Hc value of sample is 0kA/m, specific saturation magnetization б
xBe 4.50AM
2/ Kg.
Embodiment 3
Nano magnetic gathers chemotherapy medicine composition and contains I
131Being prepared as follows of Mg-Fe-AlLDH:
(1) ferric nitrate, magnesium nitrate, aluminum nitrate are dissolved in 100 ml waters according to the mixed in molar ratio of 1:1:1;
(2) get NaOH2.0 gram, Na in addition
2CO
38.5 gram is dissolved in 200 ml waters;
(3) under vigorous stirring, the nitrate mixed solution that step (1) is formed is quickly poured in the alkali liquor of step (2) formation, stirs 10 hours in 120 ℃; Precipitation is after filtration, washing back is dry, obtains MgAlFe(III) brucite;
(4) the hydrotalcite sample ultra-sonic dispersion of getting 10 gram steps (3) formation adds 100 milligrams of NaI in 200 ml waters
131, at 60-120 ℃, stir, with sedimentation and filtration, washing, obtain nano hydrotalcite NaI after the drying after ion exchange 10-20 hour
131Preparation.Particle diameter is 40-50nm, and the magnetic coercive force Hc value of sample is 0kA/m, specific saturation magnetization б
xBe 4.37AM
2/ Kg.
Embodiment 4
Nano magnetic gathers chemotherapy medicine composition and contains I
131Being prepared as follows of Mg-Fe-AlLDH:
(1) ferrous nitrate, magnesium nitrate, aluminum nitrate are dissolved in 100 ml waters according to the stoichiometric proportion mixing of 1:1:4;
(2) get NaOH2.0 gram, Na in addition
2CO
38.5 gram is dissolved in 200 ml waters;
(3) under vigorous stirring, the nitrate mixed solution that step (1) is formed is quickly poured in the alkali liquor of step (2) formation, under the nitrogen protection (secluding air), 40 ℃, stirs 20 hours; Precipitation is after filtration, washing back is dry, obtains MgAlFe(III) brucite;
(4) get 10 gram hydrotalcite sample ultra-sonic dispersion in 200 ml waters, add 100 milligrams of NaI
131, at 40-120 ℃, stir, with sedimentation and filtration, washing, obtain nano hydrotalcite NaI after the drying after ion exchange 10-20 hour
131Preparation.The sample particle diameter is 20-50nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 4.25AM
2/ Kg.
Embodiment 5
Nano magnetic gathers chemotherapy medicine composition and contains I
131Being prepared as follows of Zn-FeLDH:
(1) zinc nitrate, ferric nitrate are dissolved in 100 ml waters according to the mixed in molar ratio of 2:1, add 200 milligrams of NaI
131, stir, standby;
(2) get the NaOH3.2 gram in addition and be dissolved in 200 ml waters, form NaOH solution, standby;
(3) under the vigorous stirring; the zinc nitrate of step (1) formation and the mixed solution of ferric nitrate are quickly poured in the NaOH solution of step (2) formation; under the nitrogen protection (secluding air); ageing 10-20 hour; precipitation moves into hydrothermal reaction kettle after filtering; in 120 ℃, hydro-thermal reaction 20 hours, product is after filtration, obtain nano hydrotalcite NaI after the washing, drying
131Preparation.Particle diameter is 30-50nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 4.42AM
2/ Kg.
Embodiment 6
Nano magnetic gathers chemotherapy medicine composition and contains P
32Being prepared as follows of Zn-FeLDH:
(1) zinc nitrate, ferric nitrate are dissolved in 100 ml waters according to the stoichiometric proportion mixing of 1:2, add 200 milligrams of NaH
2P
32O4(is available from Shanghai reagent company of traditional Chinese medicines group), stir, standby;
(2) get the NaOH3.2 gram in addition and be dissolved in 200 ml waters, form NaOH solution, standby;
(3) under the vigorous stirring, mixing 98 solution that step (1) is formed are quickly poured into the NaOH solution that step (2) forms, and under 60-100 ℃, nitrogen protection, ageing 10-20 hour, product after filtration, obtained nano hydrotalcite P after the washing, drying
32Preparation.Particle diameter is 30-60nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 3.87AM
2/ Kg.
Embodiment 7
Nano magnetic gathers chemotherapy medicine composition and contains I
131Being prepared as follows of Mg-FeLDH:
(1) ferric nitrate, magnesium nitrate are dissolved in 100 ml waters according to the mixed in molar ratio of 2:1;
(2) get NaOH2.0 gram, Na in addition
2CO
38.5 gram is dissolved in 200 ml waters;
(3) under vigorous stirring, the nitrate mixed solution that step (1) is formed is quickly poured in the alkali liquor of step (2) formation, stirs 12 hours down in 80 ℃.Precipitation is after filtration, washing back is dry, obtains MgFe(III) brucite.
(4) get 10 gram hydrotalcite sample ultra-sonic dispersion in 200 ml waters, add 100 milligrams of NaH
2P
32O
4, after under the stirring under 60-100 ℃ ion exchange 10-20 hour, with sedimentation and filtration, washing, obtain nano hydrotalcite P after the drying
32Preparation.Particle diameter is 20-50nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 4.10AM
2/ Kg.
Embodiment 8
Nano magnetic gathers chemotherapy medicine composition and contains I
131Being prepared as follows of Mg-FeLDH:
(1) iron sulfate, magnesium sulfate are dissolved in 100 ml waters according to the mixed in molar ratio of 2:1, form the mixed solution of iron sulfate and magnesium sulfate, standby;
(2) get NaOH2.0 gram, Na
2CO
38.5 gram is dissolved in 200 ml waters, forms NaOH and Na
2CO
3Mixed solution, standby;
(3) under vigorous stirring, the sulfate mixed solution that step (1) is formed is quickly poured in the alkali liquor of step (2) formation, stirs 12 hours down in 80 ℃; Precipitation is after filtration, washing back is dry, obtains MgFe(III) brucite;
(4) get 10 gram hydrotalcite sample ultra-sonic dispersion in 200 ml waters, add 100 milligrams of NaI
131(available from Shanghai reagent company of traditional Chinese medicines group) 40-120 ℃ of stirring, ion exchange 10-20 hour, with sedimentation and filtration, washing, obtains nano hydrotalcite NaI after the drying
131Preparation.Particle diameter is 20-50nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 3.82AM
2/ Kg.
Embodiment 9
Nano magnetic gathers chemotherapy medicine composition and contains I
131Being prepared as follows of Zn-FeLDH:
(1) iron sulfate, zinc sulfate are dissolved in 100 ml waters according to the mixed in molar ratio of 1:2, add 200 milligrams of NaI
131, stir, standby;
(2) get the NaOH3.2 gram and be dissolved in 200 ml waters, form NaOH solution, standby;
(3) under the vigorous stirring; the mixed solution that step (1) is formed is quickly poured into the NaOH solution that middle step (2) forms; under 120 ℃, nitrogen protection (secluding air), ageing 10 hours, product is after filtration, obtain nano hydrotalcite NaI after the washing, drying
131Preparation.Particle diameter is 30-50nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 3.79AM
2/ Kg.
Embodiment 10
Nano magnetic gathers chemotherapy medicine composition and contains I
131Being prepared as follows of Mg-Fe-AlLDH:
(1) iron sulfate, magnesium sulfate, aluminum sulfate are dissolved in 100 ml waters according to the mixed in molar ratio of 1:1:1;
(2) get NaOH2.0 gram, Na in addition
2CO
38.5 gram is dissolved in 200 ml waters;
(3) under vigorous stirring, the sulfate mixed solution that step (1) is formed is quickly poured in the alkali liquor of step (2) formation, stirs 20 hours in 120 ℃; Precipitation is after filtration, washing back is dry, obtains MgAlFe(III) brucite;
(4) the hydrotalcite sample ultra-sonic dispersion of getting 10 gram steps (3) formation adds 100 milligrams of NaI in 200 ml waters
131, at 60-120 ℃, stir, with sedimentation and filtration, washing, obtain nano hydrotalcite NaI after the drying after ion exchange 10-20 hour
131Preparation.Particle diameter is 30-50nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 3.63AM
2/ Kg.
Embodiment 11
Nano magnetic gathers chemotherapy medicine composition and contains I
131Being prepared as follows of Mg-Fe-AlLDH:
(1) ferrous sulfate, magnesium sulfate, aluminum sulfate are dissolved in 100 ml waters according to the stoichiometric proportion mixing of 1:1:4;
(2) get NaOH2.0 gram, Na in addition
2CO
38.5 gram is dissolved in 200 ml waters;
(3) under vigorous stirring, the sulfate mixed solution that step (1) is formed is quickly poured in the alkali liquor of step (2) formation, in 100 ℃, stirs 15 hours; Precipitation is after filtration, washing back is dry, obtains MgAlFe(III) brucite;
(4) get 10 gram hydrotalcite sample ultra-sonic dispersion in 200 ml waters, add 100 milligrams of NaI
131, at 40-120 ℃, stir, with sedimentation and filtration, washing, obtain nano hydrotalcite NaI after the drying after ion exchange 10-20 hour
131Preparation.Particle diameter is 40-60nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 3.87AM
2/ Kg.
Embodiment 12
Nano magnetic gathers chemotherapy medicine composition and contains I
131Being prepared as follows of Zn-FeLDH:
(1) zinc sulfate, iron sulfate are dissolved in 100 ml waters according to the mixed in molar ratio of 1:2, add 200 milligrams of NaI
131, stir, standby;
(2) get the NaOH3.2 gram in addition and be dissolved in 200 ml waters, form NaOH solution, standby;
(3) under the vigorous stirring; the zinc sulfate of step (1) formation and the mixed solution of iron sulfate are quickly poured in the NaOH solution of step (2) formation; under the nitrogen protection (secluding air); ageing 10-20 hour; precipitation moves into hydrothermal reaction kettle after filtering; in 120 ℃, hydro-thermal reaction 48 hours, product is after filtration, obtain nano hydrotalcite NaI after the washing, drying
131Preparation.Particle diameter is 40-60nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 3.54AM
2/ Kg.
Embodiment 13
Nano magnetic gathers chemotherapy medicine composition and contains P
32Being prepared as follows of Zn-FeLDH:
(1) zinc sulfate, iron sulfate are dissolved in 100 ml waters according to the stoichiometric proportion mixing of 1:2, add 200 milligrams of NaH
2P
32O4(is available from Shanghai reagent company of traditional Chinese medicines group), stir, standby;
(2) get the NaOH3.2 gram in addition and be dissolved in 200 ml waters, form NaOH solution, standby;
(3) under the vigorous stirring, the mixed solution that step (1) is formed is quickly poured into the NaOH solution that step (2) forms, under 100 ℃, nitrogen protection, and ageing 20 hours, product is after filtration, obtain nano hydrotalcite P after the washing, drying
32Preparation.Particle diameter is 30-60nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 3.63AM
2/ Kg.
Embodiment 14
Nano magnetic gathers chemotherapy medicine composition and contains P
32Being prepared as follows of Mg-FeLDH:
(1) iron sulfate, magnesium sulfate are dissolved in 100 ml waters according to the mixed in molar ratio of 2:1;
(2) get NaOH2.0 gram, Na in addition
2CO
38.5 gram is dissolved in 200 ml waters;
(3) under vigorous stirring, the sulfate mixed solution that step (1) is formed is quickly poured in the alkali liquor of step (2) formation, stirs 12 hours down in 80 ℃.Precipitation is after filtration, washing back is dry, obtains MgFe(III) brucite.
(4) get 10 gram hydrotalcite sample ultra-sonic dispersion in 200 ml waters, add 100 milligrams of NaH
2P
32O
4, after under the stirring under 60-100 ℃ ion exchange 10-20 hour, with sedimentation and filtration, washing, obtain nano hydrotalcite P after the drying
32Preparation.Particle diameter is 20-60nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 3.55AM
2/ Kg.
Embodiment 15
Nano magnetic gathers chemotherapy medicine composition and contains I
131Being prepared as follows of Mg-FeLDH:
(1) iron chloride, magnesium chloride are dissolved in 100 ml waters according to the mixed in molar ratio of 2:1, form the mixed solution of iron chloride and magnesium chloride, standby;
(2) get NaOH2.0 gram, Na
2CO
38.5 gram is dissolved in 200 ml waters, forms NaOH and Na
2CO
3Mixed solution, standby;
(3) under vigorous stirring, the chlorate mixed solution that step (1) is formed is quickly poured in the alkali liquor of step (2) formation, stirs 48 hours down in 80 ℃; Precipitation is after filtration, washing back is dry, obtains MgFe(III) brucite;
(4) get 10 gram hydrotalcite sample ultra-sonic dispersion in 200 ml waters, add 100 milligrams of NaI
131(available from Shanghai reagent company of traditional Chinese medicines group) 40-120 ℃ of stirring, ion exchange 10-20 hour, with sedimentation and filtration, washing, obtains nano hydrotalcite NaI after the drying
131Preparation.Particle diameter is 30-50nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 3.64AM
2/ Kg.
Embodiment 16
Nano magnetic gathers chemotherapy medicine composition and contains I
131Being prepared as follows of Zn-FeLDH:
(1) iron chloride, zinc chloride are dissolved in 100 ml waters according to the mixed in molar ratio of 1:3, add 200 milligrams of NaI
131, stir, standby;
(2) get the NaOH3.2 gram and be dissolved in 200 ml waters, form NaOH solution, standby;
(3) under the vigorous stirring; the mixed solution that step (1) is formed is quickly poured into the NaOH solution that middle step (2) forms; under 60 ℃, nitrogen protection (secluding air), ageing 15 hours, product is after filtration, obtain nano hydrotalcite NaI after the washing, drying
131Preparation.Particle diameter is 30-50nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 3.52AM
2/ Kg.
Embodiment 17
Nano magnetic gathers chemotherapy medicine composition and contains I
131Being prepared as follows of Mg-Fe-AlLDH:
(1) iron chloride, magnesium chloride, aluminum chloride are dissolved in 100 ml waters according to the mixed in molar ratio of 1:1:1;
(2) get NaOH2.0 gram, Na in addition
2CO
38.5 gram is dissolved in 200 ml waters;
(3) under vigorous stirring, the chlorate mixed solution that step (1) is formed is quickly poured in the alkali liquor of step (2) formation, stirs 18 hours in 120 ℃; Precipitation is after filtration, washing back is dry, obtains MgAlFe(III) brucite;
(4) the hydrotalcite sample ultra-sonic dispersion of getting 10 gram steps (3) formation adds 100 milligrams of NaI in 200 ml waters
131, at 60-120 ℃, stir, with sedimentation and filtration, washing, obtain nano hydrotalcite NaI after the drying after ion exchange 10-20 hour
131Preparation.Particle diameter is 30-50nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 3.92AM
2/ Kg.
Embodiment 18
Nano magnetic gathers chemotherapy medicine composition and contains I
131Being prepared as follows of Mg-Fe-AlLDH:
(1) ferrous chloride, magnesium chloride, aluminum chloride are dissolved in 100 ml waters according to the stoichiometric proportion mixing of 1:1:4;
(2) get NaOH2.0 gram, Na in addition
2CO
38.5 gram is dissolved in 200 ml waters;
(3) under vigorous stirring, the chlorate mixed solution that step (1) is formed is quickly poured in the alkali liquor of step (2) formation, in 120 ℃, stirs 20 hours; Precipitation is after filtration, washing back is dry, obtains MgAlFe(III) brucite;
(4) get 10 gram hydrotalcite sample ultra-sonic dispersion in 200 ml waters, add 100 milligrams of NaI
131, at 40-120 ℃, stir, with sedimentation and filtration, washing, obtain nano hydrotalcite NaI after the drying after ion exchange 10-20 hour
131Preparation.Particle diameter is 30-50nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 4.01AM
2/ Kg.
Embodiment 19
Nano magnetic gathers chemotherapy medicine composition and contains I
131Being prepared as follows of Zn-FeLDH:
(1) zinc chloride, iron chloride are dissolved in 100 ml waters according to the mixed in molar ratio of 1:2, add 0.4 milligram of NaI
131, stir, standby;
(2) get the NaOH3.2 gram in addition and be dissolved in 200 ml waters, form NaOH solution, standby;
(3) under the vigorous stirring; the zinc chloride of step (1) formation and the mixed solution of iron chloride are quickly poured in the NaOH solution of step (2) formation; under the nitrogen protection (secluding air); ageing 10-20 hour; precipitation moves into hydrothermal reaction kettle after filtering; in 120 ℃, hydro-thermal reaction 20 hours, product is after filtration, obtain nano hydrotalcite NaI after the washing, drying
131Preparation.Particle diameter is 20-50nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 4.08AM
2/ Kg.
Embodiment 20
Nano magnetic gathers chemotherapy medicine composition and contains I
131Being prepared as follows of Zn-FeLDH:
(1) zinc chloride, iron chloride are dissolved in 100 ml waters according to the stoichiometric proportion mixing of 1:2, add 0.4 milligram of NaH
2P
32O4(is available from Shanghai reagent company of traditional Chinese medicines group), stir, standby;
(2) get the NaOH3.2 gram in addition and be dissolved in 200 ml waters, form NaOH solution, standby;
(3) under the vigorous stirring, the mixed solution that step (1) is formed is quickly poured into the NaOH solution that step (2) forms, under 80 ℃, nitrogen protection, and ageing 12 hours, product is after filtration, obtain nano hydrotalcite P after the washing, drying
32Preparation.Particle diameter is 30-60nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 4.13AM
2/ Kg.
Embodiment 21
Nano magnetic gathers chemotherapy medicine composition and contains I
131Being prepared as follows of Mg-FeLDH:
(1) iron chloride, magnesium chloride are dissolved in 100 ml waters according to the mixed in molar ratio of 4:1;
(2) get NaOH2.0 gram, Na in addition
2CO
38.5 gram is dissolved in 200 ml waters;
(3) under vigorous stirring, the chlorate mixed solution that step (1) is formed is quickly poured in the alkali liquor of step (2) formation, stirs 12 hours down in 80 ℃.Precipitation is after filtration, washing back is dry, obtains MgFe(III) brucite.
(4) get 10 gram hydrotalcite sample ultra-sonic dispersion in 200 ml waters, add 100 milligrams of NaH
2P
32O
4, after under the stirring under 60-100 ℃ ion exchange 10-20 hour, with sedimentation and filtration, washing, obtain nano hydrotalcite P after the drying
32Preparation.Particle diameter is 30-50nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 3.83AM
2/ Kg.
Embodiment 22
Nano magnetic gathers chemotherapy medicine composition and contains I
125Being prepared as follows of Mg-FeLDH:
(1) ferric nitrate, magnesium nitrate are dissolved in 100 ml waters according to the mixed in molar ratio of 1:4, form the mixed solution of ferric nitrate and magnesium nitrate, standby;
(2) get 200 milliliters of ammonia, standby;
(3) under vigorous stirring, the nitrate mixed solution that step (1) is formed is quickly poured in the alkali liquor of step (2) formation, stirs 12 hours down in 80 ℃; Precipitation is after filtration, washing back is dry, obtains MgFe(III) brucite;
(4) get 10 gram hydrotalcite sample ultra-sonic dispersion in 200 ml waters, add 100 milligrams of NaI
125(available from Shanghai reagent company of traditional Chinese medicines group), 100 ℃ of stirrings, ion exchange 30 hours with sedimentation and filtration, washing, obtains nano hydrotalcite NaI after the drying
125Preparation.Particle diameter is 30-50nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 3.95AM
2/ Kg.
Claims (4)
1. a nano magnetic gathers chemotherapy medicine composition, it is characterized in that molecular formula is MM'
xOH
2+3x-n σA
σ, x=0.25-4 wherein, σ=in the 0-0.1 scope and greater than 0, M=Zn
2+, Mg
2+, Fe
2+Any bivalent metal ion or the mixture of any two kinds of bivalent metal ions; M'=Al
3+, Fe
3+Any trivalent metal ion or the mixture of any two kinds of trivalent metal ions; M and M ' are not iron ion simultaneously; The mol ratio of M and M' is between 1:4 and 4:1;
A=I
125,, I
131Perhaps P
32, and A=
125I
-, A=
131I
-The time n=1; A=P
32The time n=2; With OH
-Meter; P
32Precursor be
32PO
3- 4, HP
32O
2- 4Or H
2P
32O
- 4Fe
2+Or Fe
3+Precursor be solubility nitrate, chloride or sulfate;
Be in the mixed solution that contains magnetic cation, metal cation and radioactivity anion, add alkali compounds, in 40-120 ℃ of reaction 10-20 hour, precipitation, aging, obtain the anion intercalated nano magnetic of radioactivity and gather chemotherapy medicine composition;
Perhaps in the solution that contains magnetic cation, metal cation, add alkali compounds, 70-120 ℃ was reacted 12-48 hour, precipitation, aging, formation contains brucite, pass through then and radioactivity anionic ion exchange reaction, obtain the anion intercalated nano magnetic of radioactivity and gather chemotherapy medicine composition:
The pharmaceutical composition particle diameter that obtains is at 20-60nm, and magnetic coercive force Hc value is 0kA/m, specific saturation magnetization б
xBe 3 ~ 5AM
2/ Kg can be collected at affected area, and can not form thromboembolism under magnetic field and hyperacoustic combined effect.
2.
According to claim 1Nano magnetic gathers the preparation method of chemotherapy medicine composition, it is characterized in that in the mixed solution that contains magnetic cation, metal cation and radioactivity anion, add alkali compounds, in 40-120 ℃ of reaction 10-20 hour, precipitation, aging, obtain the anion intercalated nano magnetic of radioactivity and gather chemotherapy medicine composition;
Perhaps in the solution that contains magnetic cation, metal cation, add alkali compounds, 70-120 ℃ was reacted 12-48 hour, precipitation, aging, formation contains brucite, pass through then and radioactivity anionic ion exchange reaction, obtain the anion intercalated nano magnetic of radioactivity and gather chemotherapy medicine composition;
Described magnetic cation is Fe
2+, Fe
3+Arbitrary; Described metal cation is Mg
2+, Zn
2+, Al
3+Arbitrary or both mixture; Described alkali compounds is the arbitrary or mixture of carbonate, hydroxide, ammonia.
3. nano magnetic according to claim 2 gathers the preparation method of chemotherapy medicine composition, it is characterized in that the metal cation that adopts is Mg
2+, Al
3+The time, be reflected in the air and carry out, when the metal cation that adopts is Zn
2+The time, be reflected in the nitrogen atmosphere and carry out.
4. nano magnetic according to claim 2 gathers the preparation method of chemotherapy medicine composition, and the precursor that it is characterized in that described magnetic cation is the arbitrary of solubility nitrate, chloride, sulfate; Described carbonate is sodium carbonate, and described hydroxide is sodium hydroxide.
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