CN108969765A - A kind of MnO2The preparation method of carrier coating medicine presoma 5-ALA - Google Patents
A kind of MnO2The preparation method of carrier coating medicine presoma 5-ALA Download PDFInfo
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- CN108969765A CN108969765A CN201810673235.5A CN201810673235A CN108969765A CN 108969765 A CN108969765 A CN 108969765A CN 201810673235 A CN201810673235 A CN 201810673235A CN 108969765 A CN108969765 A CN 108969765A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
- A61K41/0061—5-aminolevulinic acid-based PDT: 5-ALA-PDT involving porphyrins or precursors of protoporphyrins generated in vivo from 5-ALA
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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Abstract
The invention discloses a kind of MnO2The 5-ALA of 100mg, is dissolved in 2ml deionized water by the preparation method of carrier coating medicine presoma 5-ALA first, adjusts pH to 7 and stores；It then takes in 5-ALA, 14mg EDC, 9.3mgNHS and 4.8ml deionized water and the 25ml round-bottomed flask that 250 μ L concentration are 50mg/ml, carries out room temperature reaction 30min；0.486g BSA is then added, carries out room temperature reaction 12h；By the MnCl of 14mg2And 4H2O is dissolved in 1ml water, is added dropwise in the reaction solution of above-mentioned steps, and adjusting reaction solution pH with the NaOH of 1M is 11；It is moved into bag filter after subsequent 2h, and deionized water dialysis 3 days obtain final product, are stored in 4 DEG C of refrigerators；Using synthetic proteins and drug molecule compound, and carry out mineralising multiple response type MnO2, act not only as stabilizer mineralising synthesis MnO2, it is alternatively arranged as the carrier of 5-ALA, enhances its blood circulation time, to realize the dynamic treatment of the light of enhancing.
Description
Technical field
The present invention relates to biomedical materials field more particularly to a kind of multiple response type MnO2Carrier coating medicine forerunner
The preparation of body 5-ALA and its application in the dynamic enhancing of light.
Background technique
The dynamic treatment of light is a kind of novel method of oncotherapy.It in simple terms, is that the light source of certain wavelength is radiated at light
On quick dose, so that it is absorbed luminous energy and the oxygen molecule of part be converted to highly toxic reactive oxygen species, induced apoptosis or
The method of person's necrosis.The oxygen of photosensitizer, light source and therapentic part just becomes three big necessary components of the dynamic treatment of light.So
And because the hypermetabolism of solid tumor is horizontal, most of tumour cell is all to complete metabolism by anaerobic respiration, is caused swollen
Low-oxygen environment at oncocyte makes the dynamic treatment of the light for relying on oxygen content in passive situation.However, the variation of tumor microenvironment
On the one hand the dynamic treatment of light is affected, on the other hand the enhancing also for the dynamic treatment of light provides possibility.Solid tumor compares normal group
Position is knitted, pH value meeting slant acidity goes back original content in higher, and have the endogenous H of higher concentration2O2It generates. H2O2, in acid
Property with certain catalyst under conditions of can produce oxygen, alleviate the problem of oxygen content deficiency in the dynamic treatment of light, with this to enhance
The dynamic treatment of light provides new thinking, therefore, solves the problems, such as this kind of be particularly important.
Summary of the invention
In view of the deficiencies of the prior art, the present invention provides a kind of MnO2The preparation of carrier coating medicine presoma 5-ALA
Method.
A kind of MnO of the present invention2Carrier coating medicine presoma 5-ALA's the preparation method comprises the following steps:
The 5-ALA of 100mg is dissolved in 2ml deionized water first, pH to 7 is adjusted and stores；Then take 200-300 μ L concentration
For it is anti-to carry out room temperature in the 5-ALA of 50mg/ml, 14mg EDC, 9.3mgNHS and 4.8ml deionized water and 25ml round-bottomed flask
Answer 30min；0.486g BSA is then added, carries out room temperature reaction 12h；By the MnCl of 14mg2And 4H2O is dissolved in 1ml water, drop
It adds in the reaction solution of above-mentioned steps, and adjusting reaction solution pH with the NaOH of 1M is 11；Bag filter is moved into after subsequent 2h
In, and deionized water dialysis 3 days obtain final product, are stored in 4 DEG C of refrigerators.
Further improvement lies in that: the 5-ALA of 100mg is dissolved in 2ml deionized water first, pH to 7 is adjusted and stores；Then
Taking 250 μ L concentration is 5-ALA, 14mg EDC, 9.3mgNHS and 4.8ml deionized water and the 25ml round-bottomed flask of 50mg/ml
In, carry out room temperature reaction 30min；0.486g BSA is then added, carries out room temperature reaction 12h；By the MnCl of 14mg2And 4H2O is molten
It in 1ml water, is added dropwise in the reaction solution of above-mentioned steps, and adjusting reaction solution pH with the NaOH of 1M is 11；After subsequent 2h
It moves into bag filter, and deionized water dialysis 3 days obtain final product, are stored in 4 DEG C of refrigerators.
Further improvement lies in that: Mn2+MnO is formed under the mineralization of synthetic proteins2To catalyzing endogenous H2O2Generate oxygen
Gas prepares resulting 5-ALA and is selected as carrying medicine molecule as the intermediate product of organism synthesis porphyrin final step to play light
Movement is used.
Further improvement lies in that: the synthetic proteins carry out mineralising synthesis MnO as stabilizer2Or the carrier as 5-ALA,
Enhance its blood circulation time, to realize the dynamic treatment of the light of enhancing.
Further improvement lies in that: the synthetic proteins are blood Niu Qingbai albumen or human serum albumins or nonspecific proteins
Or the hemoglobin with targeting.
Further improvement lies in that: the predominant intermolecular forces of the synthesis are intermolecular force.
Further improvement lies in that: the model MWCO8-14kDa of the bag filter.
The beneficial effects of the present invention are:
1. compared to the material of traditional cladding 5-ALA, the MnO of mineralising2With tumor microenvironment responsiveness and the dynamic enhancing of light
Advantage, have preferable clinical value.
2. the synthesis predominant intermolecular forces are intermolecular force, complicated chemical synthesis and intermediate product it were not related to
Removal of impurities.
3. selection is the good material of biocompatibility, the toxic side effect of no material.
Detailed description of the invention
Fig. 1 is grain size distribution of the invention.
Fig. 2 is that stimuli responsive of the invention discharges [Mn2+] figure.
Fig. 3 is oxygen output figure of the invention.
Fig. 4 is cell ROS fluorogram of the invention.
Specific embodiment
In order to deepen the understanding of the present invention, the present invention is further described below in conjunction with embodiment, the present embodiment
For explaining only the invention, it is not intended to limit the scope of the present invention..
Embodiment one
The 5-ALA of 100mg is dissolved in 2ml deionized water first, pH to 7 is adjusted and stores；Then the 200 μ L concentration are taken to be
In the 5-ALA of 50mg/ml, 14mg EDC, 9.3mgNHS and 4.8ml deionized water and 25ml round-bottomed flask, reacted at room temperature
30min；0.486g BSA is then added, carries out room temperature reaction 12h；By the MnCl of 14mg2And 4H2O is dissolved in 1ml water, is added dropwise to
In the reaction solution of above-mentioned steps, and adjusting reaction solution pH with the NaOH of 1M is 11；It moves into bag filter, and goes after subsequent 2h
Ionized water dialyses 3 days and obtains final product, is stored in 4 DEG C of refrigerators.Mn2+It is formed under the mineralization of blood Niu Qingbai albumen
MnO2To catalyzing endogenous H2O2Oxygen is generated, intermediate producing of the resulting 5-ALA as organism synthesis porphyrin final step is prepared
Object is selected as carrying medicine molecule to play light movement use.The blood Niu Qingbai albumen carrys out mineralising synthesis MnO as stabilizer2Or conduct
The carrier of 5-ALA enhances its blood circulation time, to realize the dynamic treatment of the light of enhancing.The predominant intermolecular forces of the synthesis are point
Active force between son.The model MWCO8-14kDa of the bag filter.
Embodiment two
The 5-ALA of 100mg is dissolved in 2ml deionized water first, pH to 7 is adjusted and stores；Then the 250 μ L concentration are taken to be
In the 5-ALA of 50mg/ml, 14mg EDC, 9.3mgNHS and 4.8ml deionized water and 25ml round-bottomed flask, reacted at room temperature
30min；0.486g BSA is then added, carries out room temperature reaction 12h；By the MnCl of 14mg2And 4H2O is dissolved in 1ml water, is added dropwise to
In the reaction solution of above-mentioned steps, and adjusting reaction solution pH with the NaOH of 1M is 11；It moves into bag filter, and goes after subsequent 2h
Ionized water dialyses 3 days and obtains final product, is stored in 4 DEG C of refrigerators.Mn2+It is formed under the mineralization of blood Niu Qingbai albumen
MnO2To catalyzing endogenous H2O2Oxygen is generated, intermediate producing of the resulting 5-ALA as organism synthesis porphyrin final step is prepared
Object is selected as carrying medicine molecule to play light movement use.The blood Niu Qingbai albumen carrys out mineralising synthesis MnO as stabilizer2Or conduct
The carrier of 5-ALA enhances its blood circulation time, to realize the dynamic treatment of the light of enhancing.The predominant intermolecular forces of the synthesis are point
Active force between son.The model MWCO8-14kDa of the bag filter.
Embodiment three
The 5-ALA of 100mg is dissolved in 2ml deionized water first, pH to 7 is adjusted and stores；Then the 300 μ L concentration are taken to be
In the 5-ALA of 50mg/ml, 14mg EDC, 9.3mgNHS and 4.8ml deionized water and 25ml round-bottomed flask, reacted at room temperature
30min；0.486g BSA is then added, carries out room temperature reaction 12h；By the MnCl of 14mg2And 4H2O is dissolved in 1ml water, is added dropwise to
In the reaction solution of above-mentioned steps, and adjusting reaction solution pH with the NaOH of 1M is 11；It moves into bag filter, and goes after subsequent 2h
Ionized water dialyses 3 days and obtains final product, is stored in 4 DEG C of refrigerators.Mn2+It is formed under the mineralization of blood Niu Qingbai albumen
MnO2To catalyzing endogenous H2O2Oxygen is generated, intermediate producing of the resulting 5-ALA as organism synthesis porphyrin final step is prepared
Object is selected as carrying medicine molecule to play light movement use.The blood Niu Qingbai albumen carrys out mineralising synthesis MnO as stabilizer2Or conduct
The carrier of 5-ALA enhances its blood circulation time, to realize the dynamic treatment of the light of enhancing.The predominant intermolecular forces of the synthesis are point
Active force between son.The model MWCO8-14kDa of the bag filter.
Figure of description Fig. 1 is the grain size distribution of this example, it can be seen that the material stable homogeneous, size is on the left side 90nm
The right side is suitble in vivo release size.
Figure of description Fig. 2 is that the stimuli responsive of the present embodiment discharges [Mn2+] figure, as seen from the figure, in 0.01M GSH (mould
Quasi- reductive condition) and 0.01M 5.0ABS (simulating acid condition) under, [Mn]2+Cumulative release concentration is significantly larger than at any time
0.01M 7.2PBS (normal tissue condition) illustrates that there is the material tumour reproducibility and acid irritation to respond.
Figure of description Fig. 3 is the oxygen output figure of the present embodiment, and as seen from the figure, the presence of ATM can be catalyzed H202It decomposes
More oxygen are generated, move therapeutic effect so as to enhance the light at tumour.
Figure of description Fig. 4 is the cell ROS fluorogram of the present embodiment, CM-H2DCFDA is ROS fluorescent dye, green
Intensity of colour shows cell ROS yield, and ATB is no MnO2Partial material, ATM are to have MnO2Part, as can be seen from Figure,
MnO2Cell ROS yield can be enhanced, to have the potentiality for promoting the dynamic treatment of light.
The basic principles, main features and advantages of the invention have been shown and described above.The technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, and the above embodiments and description only describe originals of the invention
Reason, without departing from the spirit and scope of the present invention, various changes and improvements may be made to the invention, these changes and improvements
It all fall within the protetion scope of the claimed invention.The claimed scope of the invention is by appending claims and equivalents circle
It is fixed.
Claims (7)
1. a kind of MnO2The preparation method of carrier coating medicine presoma 5-ALA, it is characterised in that: first by the 5-ALA of 100mg
It is dissolved in 2ml deionized water, adjusts pH to 7 and store；Then to take 200-300 μ L concentration be the 5-ALA of 50mg/ml, 14mg EDC,
In 9.3mgNHS and 4.8ml deionized water and 25ml round-bottomed flask, room temperature reaction 30min is carried out；0.486g BSA is then added,
Carry out room temperature reaction 12h；By the MnCl of 14mg2And 4H2O is dissolved in 1ml water, is added dropwise in the reaction solution of above-mentioned steps, and uses 1M
NaOH come adjust reaction solution pH be 11；It is moved into bag filter after subsequent 2h, and deionized water dialysis 3 days obtain final product,
It is stored in 4 DEG C of refrigerators.
2. a kind of MnO as described in claim 12The preparation method of carrier coating medicine presoma 5-ALA, it is characterised in that: it is first
First the 5-ALA of 100mg is dissolved in 2ml deionized water, pH to 7 is adjusted and stores；Then taking 250 μ L concentration is the 5- of 50mg/ml
In ALA, 14mg EDC, 9.3mgNHS and 4.8ml deionized water and 25ml round-bottomed flask, room temperature reaction 30min is carried out；Then add
Enter 0.486g BSA, carries out room temperature reaction 12h；By the MnCl of 14mg2And 4H2O is dissolved in 1ml water, is added dropwise to the anti-of above-mentioned steps
It answers in liquid, and adjusting reaction solution pH with the NaOH of 1M is 11；It is moved into bag filter after subsequent 2h, and deionized water dialysis 3
It obtains final product, is stored in 4 DEG C of refrigerators.
3. a kind of MnO as claimed in claim 1 or 22The preparation method of carrier coating medicine presoma 5-ALA, feature exist
In: Mn2+MnO is formed under the mineralization of synthetic proteins2To catalyzing endogenous H2O2Oxygen is generated, resulting 5-ALA is prepared and makees
It is selected as carrying medicine molecule for the intermediate product that organism synthesizes porphyrin final step to play light movement use.
4. a kind of MnO as claimed in claim 32The preparation method of carrier coating medicine presoma 5-ALA, it is characterised in that: institute
Synthetic proteins are stated as stabilizer and carry out mineralising synthesis MnO2Or the carrier as 5-ALA.
5. a kind of MnO as claimed in claim 42The preparation method of carrier coating medicine presoma 5-ALA, it is characterised in that: institute
Stating synthetic proteins is blood Niu Qingbai albumen or human serum albumins or nonspecific proteins or the hemoglobin with targeting.
6. a kind of MnO as claimed in claim 32The preparation method of carrier coating medicine presoma 5-ALA, it is characterised in that: it should
The predominant intermolecular forces of synthesis are intermolecular force.
7. a kind of MnO as claimed in claim 1 or 22The preparation method of carrier coating medicine presoma 5-ALA, feature exist
In: the model MWCO8-14kDa of the bag filter.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111840564A (en) * | 2020-07-31 | 2020-10-30 | 曲阜师范大学 | Manganese dioxide-based nano-drug carrier and preparation method and application thereof |
| CN113546057A (en) * | 2021-06-07 | 2021-10-26 | 昆明理工大学 | Indocyanine green composite nanoparticles and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107343957A (en) * | 2017-07-18 | 2017-11-14 | 中南大学 | A kind of black phosphorus/manganese dioxide composite nano materials and its preparation method and application |
| CN108187072A (en) * | 2018-02-05 | 2018-06-22 | 中国人民解放军陆军军医大学第三附属医院（野战外科研究所） | The nano material of manganese dioxide and preparation method and application that albumin is stablized |
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2018
- 2018-06-27 CN CN201810673235.5A patent/CN108969765A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107343957A (en) * | 2017-07-18 | 2017-11-14 | 中南大学 | A kind of black phosphorus/manganese dioxide composite nano materials and its preparation method and application |
| CN108187072A (en) * | 2018-02-05 | 2018-06-22 | 中国人民解放军陆军军医大学第三附属医院（野战外科研究所） | The nano material of manganese dioxide and preparation method and application that albumin is stablized |
Non-Patent Citations (2)
| Title |
|---|
| QIAN CHEN ET AL: "Intelligent Albumin–MnO2 Nanoparticles as pH-/H2O2-Responsive Dissociable Nanocarriers to Modulate Tumor Hypoxia for Effective Combination Therapy", 《ADVANCED MATERIALS》 * |
| 罗荣辉 等著: "《生物医学光子学》", 31 August 2008, 吉林大学出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111840564A (en) * | 2020-07-31 | 2020-10-30 | 曲阜师范大学 | Manganese dioxide-based nano-drug carrier and preparation method and application thereof |
| CN113546057A (en) * | 2021-06-07 | 2021-10-26 | 昆明理工大学 | Indocyanine green composite nanoparticles and preparation method and application thereof |
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Application publication date: 20181211 |