CN112414985A - Analysis method for detecting drug distribution and application thereof - Google Patents
Analysis method for detecting drug distribution and application thereof Download PDFInfo
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- CN112414985A CN112414985A CN202011233334.5A CN202011233334A CN112414985A CN 112414985 A CN112414985 A CN 112414985A CN 202011233334 A CN202011233334 A CN 202011233334A CN 112414985 A CN112414985 A CN 112414985A
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- 238000009513 drug distribution Methods 0.000 title claims abstract description 24
- 238000004458 analytical method Methods 0.000 title claims abstract description 22
- 239000003814 drug Substances 0.000 claims abstract description 45
- 241000700159 Rattus Species 0.000 claims description 47
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 27
- 229940079593 drug Drugs 0.000 claims description 21
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 10
- 239000001569 carbon dioxide Substances 0.000 claims description 10
- 235000011089 carbon dioxide Nutrition 0.000 claims description 7
- QSWSZIQYTSNSNR-UHFFFAOYSA-N carbon dioxide;hexane Chemical compound O=C=O.CCCCCC QSWSZIQYTSNSNR-UHFFFAOYSA-N 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 6
- 238000002474 experimental method Methods 0.000 claims description 6
- 229920002799 BoPET Polymers 0.000 claims description 5
- 239000005041 Mylar™ Substances 0.000 claims description 5
- 239000000853 adhesive Substances 0.000 claims description 5
- 230000001070 adhesive effect Effects 0.000 claims description 5
- 230000008014 freezing Effects 0.000 claims description 5
- 238000007710 freezing Methods 0.000 claims description 5
- 238000003384 imaging method Methods 0.000 claims description 5
- 238000004806 packaging method and process Methods 0.000 claims description 5
- 239000012085 test solution Substances 0.000 claims description 5
- KUAZQDVKQLNFPE-UHFFFAOYSA-N thiram Chemical compound CN(C)C(=S)SSC(=S)N(C)C KUAZQDVKQLNFPE-UHFFFAOYSA-N 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 4
- 230000002285 radioactive effect Effects 0.000 claims description 3
- 238000003556 assay Methods 0.000 claims description 2
- 238000001514 detection method Methods 0.000 abstract description 2
- 210000000056 organ Anatomy 0.000 abstract description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 210000002977 intracellular fluid Anatomy 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/645—Specially adapted constructive features of fluorimeters
- G01N21/6456—Spatial resolved fluorescence measurements; Imaging
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
- G01N2021/6439—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks
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- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Optics & Photonics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention belongs to the technical field of drug distribution detection, and particularly relates to an analysis method for detecting drug distribution and application thereof. The analysis method for detecting the distribution of the medicine and the application thereof can observe the distribution condition of the medicine by adopting a multi-stage and multi-medicine-taking time sample, the analysis result is more comprehensive, the distribution part of the medicine can be fully known in practical application, the medicine is improved, the medicine is more concentrated on the designated target spot, and the influence on other organs is reduced.
Description
Technical Field
The invention relates to the technical field of drug distribution detection, in particular to an analysis method for detecting drug distribution and application thereof.
Background
The drug distribution refers to the process of the drug after absorption and circulating to interstitial fluid and intracellular fluid of each tissue along with blood, and the drug distribution research is an important component of pharmacokinetic research and can be used for predicting the curative effect and the in vivo accumulation degree of the drug and guiding clinical medication, structural modification and dosage form design. In the existing analysis method, the types of the adopted samples are not combined, the analysis result is not comprehensive enough, the medicine cannot be improved, and the target point of the medicine cannot be concentrated.
Disclosure of Invention
This section is for the purpose of summarizing some aspects of embodiments of the invention and to briefly introduce some preferred embodiments. In this section, as well as in the abstract and the title of the invention of this application, simplifications or omissions may be made to avoid obscuring the purpose of the section, the abstract and the title, and such simplifications or omissions are not intended to limit the scope of the invention.
To solve the above technical problem, according to an aspect of the present invention, the present invention provides the following technical solutions:
an assay for detecting drug distribution comprising the steps of:
s1: taking experimental rats in different physiological stages, and feeding the rats with the same amount of radiolabeled drugs;
s2: placing rats with different administration time in carbon dioxide, and killing the rats by carbon dioxide inhalation death;
s3: freezing the rat specimen in hexane-carbon dioxide dry ice for 20-30min, and slicing the cooled rat specimen, wherein the thickness of the slices is uniform and is 25-50 μm;
s4: packaging the cut sheet layer by adopting Mylar adhesive paper, and pretreating the sheet layer by adopting Nobecutan test solution;
s5: the distribution of the drug was observed by placing the sliced sample on an imaging plate and observing the fluorescent site through a microscope.
Use of an analytical method for detecting drug distribution, comprising the steps of:
s1: by mixing the specified drugs with radioactive labels and placing into rats;
s2: analyzing the distribution condition of the drug in the rat body through a drug analysis experiment, and recording the distribution condition;
s3: through the distribution condition, the treatment area of the medicine is obtained, so that the treatment effect of the medicine is improved.
As a preferable embodiment of the analytical method for detecting drug distribution according to the present invention, wherein: the rats used in step S2 include five time points, which are 15min, 1h, 4h, 24h and 72h, respectively.
As a preferable embodiment of the analytical method for detecting drug distribution according to the present invention, wherein: the rats used in said step S1 were selected from 3-5 male rats, 3-5 pregnant and non-pregnant female rats at each time point for the experiment.
As a preferable embodiment of the analytical method for detecting drug distribution according to the present invention, wherein: the radiolabeled isotope used in step S1 is14C。
As a preferable embodiment of the analytical method for detecting drug distribution according to the present invention, wherein: the temperature of the hexane-carbon dioxide dry ice in the step S3 was-70 ℃.
Compared with the prior art: through putting into the animal for experiments with the radioisotope, and through making the experimental animal section of different physiological stages and different dosing time, after carrying out the physical fixation method to the section, observe the section again, thereby obtain the distribution condition of medicine, and fully know the distribution position of medicine according to the distribution condition, and improve the effect of medicine, make the medicine more concentrate on appointed target, this an analytical method and its application for detecting medicine distribution, not only can be through adopting the sample of multistage and many dosing time, observe the distribution condition of medicine, the analysis result is more comprehensive, and can fully know the distribution position of medicine in practical application, and improve the medicine, make the medicine more concentrate on appointed target, reduce the influence to other organs.
Detailed Description
The present invention will be described in detail with reference to the following embodiments in order to make the aforementioned objects, features and advantages of the invention more comprehensible.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways than those specifically described herein, and it will be apparent to those of ordinary skill in the art that the present invention may be practiced without departing from the spirit and scope of the present invention, and therefore the present invention is not limited to the specific embodiments disclosed below.
In order to make the objects, technical solutions and advantages of the present invention more apparent, embodiments of the present invention will be described in further detail below.
Example 1:
s1: selecting 5 male experimental rats, and feeding the rats with the same amount14C a radiolabeled drug;
s2: placing rats with different administration time of 15min, 1h, 4h, 24h and 72h in carbon dioxide, and killing the rats by carbon dioxide inhalation death;
s3: placing the rat specimen into hexane-carbon dioxide dry ice at-70 ℃ for freezing for 30min, and slicing the cooled rat specimen, wherein the thickness of the slices is uniform and is 30 micrometers;
s4: packaging the cut sheet layer by adopting Mylar adhesive paper, and pretreating the sheet layer by adopting Nobecutan test solution;
s5: the slice sample is placed on an imaging plate, and the fluorescent part is observed through a microscope, so that the distribution condition of the drug is observed, and the drug distribution condition of a male rat is obtained;
example two
S1: selecting 5 non-pregnant female rats, and feeding the same amount of rats14C a radiolabeled drug;
s2: placing rats with different administration time of 15min, 1h, 4h, 24h and 72h in carbon dioxide, and killing the rats by carbon dioxide inhalation death;
s3: placing the rat specimen into hexane-carbon dioxide dry ice at-70 ℃ for freezing for 30min, and slicing the cooled rat specimen, wherein the thickness of the slices is uniform and is 30 micrometers;
s4: packaging the cut sheet layer by adopting Mylar adhesive paper, and pretreating the sheet layer by adopting Nobecutan test solution;
s5: the slice sample is placed on an imaging plate, and the fluorescent part is observed through a microscope, so that the distribution condition of the drug is observed, and the drug distribution condition of a female rat is obtained;
EXAMPLE III
S1: selecting 5 pregnant female experimental rats, and feeding the rats with the same amount of feed14C a radiolabeled drug;
s2: placing rats with different administration time of 15min, 1h, 4h, 24h and 72h in carbon dioxide, and killing the rats by carbon dioxide inhalation death;
s3: placing the rat specimen into hexane-carbon dioxide dry ice at-70 ℃ for freezing for 30min, and slicing the cooled rat specimen, wherein the thickness of the slices is uniform and is 30 micrometers;
s4: packaging the cut sheet layer by adopting Mylar adhesive paper, and pretreating the sheet layer by adopting Nobecutan test solution;
s5: the drug distribution of the pregnant female rat and the drug distribution of the embryo were obtained by placing the sliced sample on an imaging plate and observing the fluorescent site through a microscope to observe the drug distribution.
Application of analysis method for detecting drug distribution
S1: by mixing the specified drugs with radioactive labels and placing into rats;
s2: analyzing the distribution condition of the drug in the rat body through a drug analysis experiment, and recording the distribution condition;
s3: through the distribution condition, the treatment area of the medicine is obtained, so that the treatment effect of the medicine is improved.
By analyzing the distribution condition of the medicine, the treatment effect of the medicine is conveniently improved.
While the invention has been described above with reference to an embodiment, various modifications may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In particular, the various features of the disclosed embodiments of the invention may be used in any combination, provided that no structural conflict exists, and the combinations are not exhaustively described in this specification merely for the sake of brevity and resource conservation. Therefore, it is intended that the invention not be limited to the particular embodiments disclosed, but that the invention will include all embodiments falling within the scope of the appended claims.
Claims (6)
1. An analytical method for detecting drug distribution, comprising the steps of:
s1: taking experimental rats in different physiological stages, and feeding the rats with the same amount of radiolabeled drugs;
s2: placing rats with different administration time in carbon dioxide, and killing the rats by carbon dioxide inhalation death;
s3: freezing the rat specimen in hexane-carbon dioxide dry ice for 20-30min, and slicing the cooled rat specimen, wherein the thickness of the slices is uniform and is 25-50 μm;
s4: packaging the cut sheet layer by adopting Mylar adhesive paper, and pretreating the sheet layer by adopting Nobecutan test solution;
s5: the distribution of the drug was observed by placing the sliced sample on an imaging plate and observing the fluorescent site through a microscope.
2. Use of an analytical method for detecting drug distribution, comprising the steps of:
s1: by mixing the specified drugs with radioactive labels and placing into rats;
s2: analyzing the distribution condition of the drug in the rat body through a drug analysis experiment, and recording the distribution condition;
s3: through the distribution condition, the treatment area of the medicine is obtained, so that the treatment effect of the medicine is improved.
3. The method according to claim 1, wherein the rat used in step S2 includes five time points, 15min, 1h, 4h, 24h and 72h respectively.
4. The assay for detecting drug distribution of claim 1, wherein the rats used in step S1 are selected for experiments with 3-5 male rats, 3-5 pregnant and non-pregnant female rats at each time point.
5. The method as claimed in claim 1, wherein the radiolabeled isotope used in step S1 is14C。
6. The analysis method for detecting drug distribution according to claim 1, wherein the temperature of the hexane-carbon dioxide dry ice in the step S3 is-70 ℃.
Priority Applications (1)
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CN202011233334.5A CN112414985A (en) | 2020-11-06 | 2020-11-06 | Analysis method for detecting drug distribution and application thereof |
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CN202011233334.5A CN112414985A (en) | 2020-11-06 | 2020-11-06 | Analysis method for detecting drug distribution and application thereof |
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH1137959A (en) * | 1997-07-22 | 1999-02-12 | Seitai Kagaku Kenkyukai | Method for detecting distribution of element in living body |
US20060228296A1 (en) * | 2002-05-31 | 2006-10-12 | Commissariat A L'energie Atomique | Method of screening groups of radioactive molecules and applications thereof |
JP2017194289A (en) * | 2016-04-18 | 2017-10-26 | 日立Geニュークリア・エナジー株式会社 | Radioactivity distribution analysis system and radioactivity distribution analysis method |
CN107389776A (en) * | 2017-07-18 | 2017-11-24 | 广州新诚生物科技有限公司 | A kind of analysis method and its application for being used to detect drug distribution |
CN111562278A (en) * | 2020-05-22 | 2020-08-21 | 江苏万略医药科技有限公司 | Quantitative whole-body autoradiography drug distribution tracking method |
-
2020
- 2020-11-06 CN CN202011233334.5A patent/CN112414985A/en active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH1137959A (en) * | 1997-07-22 | 1999-02-12 | Seitai Kagaku Kenkyukai | Method for detecting distribution of element in living body |
US20060228296A1 (en) * | 2002-05-31 | 2006-10-12 | Commissariat A L'energie Atomique | Method of screening groups of radioactive molecules and applications thereof |
JP2017194289A (en) * | 2016-04-18 | 2017-10-26 | 日立Geニュークリア・エナジー株式会社 | Radioactivity distribution analysis system and radioactivity distribution analysis method |
CN107389776A (en) * | 2017-07-18 | 2017-11-24 | 广州新诚生物科技有限公司 | A kind of analysis method and its application for being used to detect drug distribution |
CN111562278A (en) * | 2020-05-22 | 2020-08-21 | 江苏万略医药科技有限公司 | Quantitative whole-body autoradiography drug distribution tracking method |
Non-Patent Citations (1)
Title |
---|
姚倩 等: ""药物分布检测技术研究进展"", 《2008年中国药学会学术年会暨第八届中国药师周论文集》 * |
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Application publication date: 20210226 |