CN1314456C - Medicament box of 2beta-[N,N'-di(2-mercaptoethyl) ethylene diamine] methyl-3 beta-(4- chlorphenyl) tropane - Google Patents
Medicament box of 2beta-[N,N'-di(2-mercaptoethyl) ethylene diamine] methyl-3 beta-(4- chlorphenyl) tropane Download PDFInfo
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- CN1314456C CN1314456C CNB2005100946353A CN200510094635A CN1314456C CN 1314456 C CN1314456 C CN 1314456C CN B2005100946353 A CNB2005100946353 A CN B2005100946353A CN 200510094635 A CN200510094635 A CN 200510094635A CN 1314456 C CN1314456 C CN 1314456C
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- medicine box
- tropane
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- chlorphenyl
- gluceptate
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Abstract
The present invention relates to a technetium [[99m]<Tc>] labeling kit of 2 beta-[N, N'-double (2-mercaptoethyl) ethylene diamine] methyl-3 beta-(4-chlorophenyl)tropane (TRODAT-1 for short), which belongs to the technical field of a single photon emission computed tomography (SPECT) imaging agent. The present invention provides a kit prescription of TRODAT-1. When used for labeling [[99m]<Tc>]], the kit prepared by the prescription has the advantages of simple operation and stable labeling rate (larger than 90%). The kit is prepared from TRODAT-1, stannous salt, glucoheptonate, edetate, a pH buffering agent, etc. according to a certain composition. No identical international report for the prescription of the kit provided by the present invention is reported.
Description
Technical field
2 β-[N, N '-two (2-mercapto ethyl) ethylene diamin(e)] methyl-3 β-(4-chlorphenyl) tropane (hereinafter to be referred as: technetium TRODAT-1) [
99mTc] labeling kit, relate to TRODAT-1 technetium [
99mTc] labeling kit prescription and technology of preparing, belong to single photon emission computed tomography (SPECT) developer technical field.
Background technology
Technetium [
99mTc]-2 β-[N, N '-two (2-mercapto ethyl) ethylene diamin(e)] methyl-3 β-(4-chlorphenyl) tropane (
99mTc-TRODAT-1) be first technetium [
99mTc] success of labelling is used for the dopamine transporter imaging agent of human body, it can be with dopamine transporter specific bond in the brain and dense gathering in striatum, distinct image is provided, the change information of prompting dopaminergic system particularly has splendid clinical practice potentiality to Parkinsonian early diagnosis to diseases associated.Since Kung H.F. reported first in 1996, carried out a large amount of pharmacology and clinical research both at home and abroad, shown good potential applicability in clinical practice.At present
99mTc-TRODAT-1 successfully is used for Parkinsonian early diagnosis and state of an illness evaluation, and also got aspect the attention deficit hyperkinetic syndrome can successful application.
Clinical practice
99mTc-TRODAT-1 requires that labeling process is simple, mark rate is more preferably greater than 90%.Kung M.P in 1997 etc. use the multistep processes preparation
99mTc-TRODAT-1, though mark rate greater than 90%, complex operation can not be promoted just and use.For the ease of clinical practice, preferably will prepare
99mThe required TRODAT-1 of Tc-TRODAT-1, Reducing agent, excipient etc. are made medicine box, simplify labeling process.For this reason, Choi S.R. etc. by the formulation of the disodiumedetate of stannous chloride, 10mg gluceptate sodium and the 840 μ g of TRODAT-1, the 32 μ g of 10 μ g froze-dried kit, set up the one-step method tagging scheme, average mark rate 90%.We find that with other research worker the medicine box shortcoming of this prescription is the mark rate instability, often is lower than 90%.In order to solve this shortcoming, Gyula Toth etc. pass through a C with behind the homemade medicine box labelling with label solution
18Pillar, the reuse eluant is removed most impurity by certain program drip washing, makes putting pure greater than 95%, provides putting of preparation height pure
99mThe method of Tc-TRODAT-1.But the method has increased operating procedure, and complicated operating process is unfavorable for promoting, and has also increased cost simultaneously.
Summary of the invention
The purpose of this invention is to provide a kind of TRODAT-1 labeling kit prescription, make mark rate stable and greater than 90%.For the shortcoming of the labeling kit that overcomes external TRODAT-1, we have designed a kind of new medicine box prescription, have added the pH buffer agent in medicine box, and improved the consumption of TRODAT-1, and make mark rate stable and greater than 90%, be beneficial to clinical practice, and operating process is simple, is convenient to promote.
Technical scheme of the present invention: the preparation method of 100 bottles of TRODAT-1 medicine boxs is as follows, take by weighing pH buffer agent 7mmol, be dissolved in the 70mL distilled water, add the gluceptate of 0.1-2.0g and the edetate of 0.05-1.00g again, tin salt dilute hydrochloric acid (0.05mol/L) the solution 0.4-10mL that adds 1mg/mL, TRODAT-1 dilute hydrochloric acid (0.05mol/L) the solution 2-20mL that adds 1mg/mL at last, adding distilled water to medicinal liquid cumulative volume again is 100ml, be sub-packed in the cillin bottle of 10ml specification by the 1.0mL/ bottle again, promptly get the TRODAT-1 medicine box after the lyophilization.The tin salt, the edetate of 0.5-10mg and the gluceptate of 1-20mg that contain TRODAT-1, the 4-100 μ g of 20-200 μ g in every medicine box.Medicine box adds that the pH value scope is 4.0-8.5 behind the 1ml distilled water.
Labeling process: get 1 of TRODAT-1 medicine box, add Na
99mTcO
4Solution 1mL places and heats 30min on the boiling water bath, gets final product after the cooling.
The assay method of mark rate is up thin layer chromatography (TLC) method.
We have also investigated when each component content changes within the specific limits in the medicine box influence to the medicine box quality, and the investigation method changes a kind of content of composition within the specific limits for the content that keeps other component is constant, carry out technetium [
99mTc] measure mark rate behind the labelling.The result shows that the component content of working as in the medicine box in following scope, can guarantee that all mark rate is greater than 90%:
TRODAT-1 20-200μg
PH value 4.0-8.5
Tin salt 4-100 μ g
Edetate 0.5-10mg
Gluceptate 1-20mg
Used tin salt is stannous chloride, stannous fluoride, stannous tartrate, Tin dibromide. or stannous citrate.
Used edetate is disodium edta or ethylene diamine tetraacetic acid sylvite.
Used gluceptate is gluceptate sodium or glucoheptonic acid potassium.
The pH buffer agent is one or more the mixture in phosphate, citrate, ammonium salt, acetate, tartrate, carbonate, borate, Barbiturate, the o-2 potassium acid salt in the medicine box.
Beneficial effect of the present invention: we think, cause the unsettled reason of medicine box mark rate of Choi S design to be: do not contain the pH buffer agent in (1) system, make that pH value can not maintain fixed value in the labeling process; (2) the TRODAT-1 consumption is very few.Because the TRODAT-1 unstable chemcial property has in preparation, transportation, storage partly even all TRODAT-1 generation decomposition is rotten.Improve to the property of the present invention is directed to: added the pH buffer agent in (1) prescription, made that pH value can maintain stationary value in the labeling process, mark rate is stable and greater than 90%, very helps clinical application; (2) improved the TRODAT-1 consumption in the medicine box, when a spot of TRODAT-1 takes place to go bad, still had the TRODAT-1 of q.s in the medicine box, guaranteed that mark rate is greater than 90%.It is simple that this medicine box also has a labeling process, the characteristics that can apply easily.The medicine box prescription that the present invention proposes does not have identical report in the world.
Description of drawings
The content of Fig. 1 .TRODAT-1 is to the influence of mark rate.
Fig. 2. tin salt content is to the influence of mark rate.
Fig. 3. edetate (EDTA) content is to the influence of mark rate.
Fig. 4. gluceptate (GH) content is to the influence of mark rate.
Fig. 5. the pH of medicine box is to the influence of mark rate.
The specific embodiment
The preparation of TRODAT-1 medicine box:
The preparation method of 100 bottles of TRODAT-1 medicine boxs is as follows: take by weighing potassium dihydrogen phosphate 2mmol, sodium hydrogen phosphate 5mmol, be dissolved in the 88mL distilled water, add the gluceptate sodium of 1.00g and the disodiumedetate of 100mg again, stannous chloride dilute hydrochloric acid (0.05mol/L) the solution 7.00mL that adds 1.00mg/mL, TRODAT-1 dilute hydrochloric acid (0.05mol/L) the solution 5.00mL that adds 1.00mg/mL at last, aseptic filtration behind the mixing, be sub-packed in the 10ml cillin bottle by the 1.00mL/ bottle again, promptly get the TRODAT-1 medicine box after the lyophilization.Contain the stannous chloride of TRODAT-1, the 70.0 μ g of 50.0 μ g, the disodiumedetate of 1.00mg and the gluceptate sodium of 10.0mg in every medicine box, add 1ml water in the medicine box after pH value be: 4.0-8.5.
The labeling method of TRODAT-1 medicine box:
Get 1 of TRODAT-1 medicine box, add the Na of new drip washing
99mTcO4 solution 1.0mL places and heats 30min on the boiling water bath, gets final product after the cooling.
Embodiment 3
The assay method of mark rate:
Up thin layer chromatography (TLC) method.
When each component content changes within the specific limits to the influence of medicine box mark rate:
Keep other component content constant by among the embodiment 1, the content that changes TRODAT-1 in the medicine box is 1-300 μ g, press the method mensuration mark rate of pressing embodiment 3 behind the method labelling of embodiment 2 again.The result as shown in Figure 1, the content of TRODAT-1 is in 20-200 μ g scope, the medicine box mark rate reaches 90%.
Embodiment 5
When each component content changes within the specific limits to the influence of medicine box mark rate:
Keep other component content constant by among the embodiment 1, tin salt is used stannous fluoride instead in the medicine box, and its content is 0.5-100 μ g, presses the method for pressing embodiment 3 behind the method labelling of embodiment 2 again and measures mark rate.The result as shown in Figure 2, the content of tin salt is in 4-100 μ g scope, the medicine box mark rate reaches 90%.
When each component content changes within the specific limits to the influence of medicine box mark rate:
Keep other component content constant by among the embodiment 1, edetate is used ethylenediamine tetraacetic acid,dipotassium salt instead in the medicine box, and its content is 0.1-20mg, presses the method for pressing embodiment 3 behind the method labelling of embodiment 2 again and measures mark rate.The result as shown in Figure 3, the content of edetate is in the 0.5-10mg scope, the medicine box mark rate reaches 90%.
Embodiment 7
When each component content changes within the specific limits to the influence of medicine box mark rate:
Keep other component content constant by among the embodiment 1, gluceptate is used glucoheptonic acid potassium instead in the medicine box, and its content is 1-20mg, presses the method for pressing embodiment 3 behind the method labelling of embodiment 2 again and measures mark rate.The result as shown in Figure 4, the content of gluceptate is in the 1-20mg scope, the medicine box mark rate reaches 90%.
The pH value of medicine box is to the influence of mark rate:
Keep other component content constant by among the embodiment 1, regulate the medicine box pH value with the pH buffer agent and in the 1-12 scope, change, press the method mensuration mark rate of pressing embodiment 3 behind the method labelling of embodiment 2 again.The result illustrates shown in 5, pH value in the 4.0-8.5 scope medicine box mark rate greater than 90%.
Used pH buffer agent is one or more the mixture in phosphate, citrate, ammonium salt, acetate, tartrate, carbonate, borate, Barbiturate, the o-2 potassium acid salt.
Claims (6)
1. the medicine box of β-[N, N '-two (2-mercapto ethyl) ethylene diamin(e)] methyl-3 β-(4-chlorphenyl) tropane, be used to carry out technetium [
99mTc] labelling, it is characterized in that consisting of: 2 β-[N, N '-two (2-mercapto ethyl) ethylene diamin(e)] methyl-3 β-(4-chlorphenyl) tropane, tin salt, gluceptate, edetate, pH buffer agent, the content range of each component is in the medicine box:
2 β-[N, N '-two (2-mercapto ethyl) ethylene diamin(e)] methyl
-3 β-(4-chlorphenyl) tropane 20-200 μ g
Tin salt 4-100 μ g
Edetate 0.5-10mg
Gluceptate 1-20mg
It is 4.0-8.5 that the pH buffer agent is regulated the pH scope.
2. medicine box according to claim 1 is characterized in that tin salt is stannous chloride, stannous fluoride, stannous tartrate, Tin dibromide. or stannous citrate.
3. medicine box according to claim 1 is characterized in that edetate is disodium edta or ethylene diamine tetraacetic acid sylvite.
4. medicine box according to claim 1 is characterized in that gluceptate is gluceptate sodium or glucoheptonic acid potassium.
5. medicine box according to claim 1 is characterized in that pH buffer agent in the medicine box is one or more the mixture in phosphate, citrate, ammonium salt, acetate, tartrate, carbonate, borate, Barbiturate, the o-2 potassium acid salt.
6. the compound method of medicine box as claimed in claim 1, it is characterized in that 100 bottle of 2 β-[N, N '-two (2-mercapto ethyl) ethylene diamin(e)] preparation method of methyl-3 β-(4-chlorphenyl) tropane medicine box is as follows, take by weighing pH buffer agent 7mmol, be dissolved in the 70mL distilled water, add the gluceptate of 0.1-2.0g and the edetate of 0.05-1.00g again, the 0.05mol/L dilute hydrochloric acid solution 0.4-10mL that adds the tin salt of 1mg/mL, the 2 β-[N that adds 1mg/mL at last, N '-two (2-mercapto ethyl) ethylene diamin(e)] the 0.05mol/L dilute hydrochloric acid solution 2-20mL of methyl-3 β-(4-chlorphenyl) tropane, adding distilled water to medicinal liquid cumulative volume again is 100ml, be sub-packed in the cillin bottle of 10ml specification by the 1.0mL/ bottle again, promptly get 2 β-[N after the lyophilization, N '-two (2-mercapto ethyl) ethylene diamin(e)] methyl-3 β-(4-chlorphenyl) tropane medicine box, the 2 β-[N that contains 20-200 μ g in every medicine box, N '-two (2-mercapto ethyl) ethylene diamin(e)] methyl-3 β-(4-chlorphenyl) tropane, the tin salt of 4-100 μ g, 0.5-10mg edetate and the gluceptate of 1-20mg, medicine box adds that the pH value scope is 4.0-8.5 behind the 1ml distilled water.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100946353A CN1314456C (en) | 2005-09-27 | 2005-09-27 | Medicament box of 2beta-[N,N'-di(2-mercaptoethyl) ethylene diamine] methyl-3 beta-(4- chlorphenyl) tropane |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100946353A CN1314456C (en) | 2005-09-27 | 2005-09-27 | Medicament box of 2beta-[N,N'-di(2-mercaptoethyl) ethylene diamine] methyl-3 beta-(4- chlorphenyl) tropane |
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| CN1762499A CN1762499A (en) | 2006-04-26 |
| CN1314456C true CN1314456C (en) | 2007-05-09 |
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| CNB2005100946353A Expired - Fee Related CN1314456C (en) | 2005-09-27 | 2005-09-27 | Medicament box of 2beta-[N,N'-di(2-mercaptoethyl) ethylene diamine] methyl-3 beta-(4- chlorphenyl) tropane |
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Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100368805C (en) * | 2006-07-31 | 2008-02-13 | 江苏省原子医学研究所 | Analysis method of mercapto amine tropine content |
| CN100485366C (en) * | 2007-04-13 | 2009-05-06 | 江苏省原子医学研究所 | A method for determining the content of 2 beta-[N, N'-bis (2-mercaptoethyl) ethylenediamine] methyl-3 beta-(4-chlorophenyl) tropane in a kit |
| CN101320014B (en) * | 2008-07-01 | 2012-11-21 | 江苏省原子医学研究所 | Analytical method for measuring raw medicine content of thiohydroxylamine tropine by non-aqueous titrimetry |
| CN101538284B (en) * | 2009-05-05 | 2011-09-07 | 北京师范大学 | Preparation method and application of 99Tcm-EDTA-MTI coordination compound |
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| US5720934A (en) * | 1992-04-30 | 1998-02-24 | Diatide, Inc. | Technetium-99M labeled peptides for imaging |
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2005
- 2005-09-27 CN CNB2005100946353A patent/CN1314456C/en not_active Expired - Fee Related
Patent Citations (5)
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| US5720934A (en) * | 1992-04-30 | 1998-02-24 | Diatide, Inc. | Technetium-99M labeled peptides for imaging |
| CN1208656A (en) * | 1998-09-04 | 1999-02-24 | 中国原子能科学研究院 | 99M TC-N, N' -diamine ethyl propylene diamine hexaacetic acid developer and application |
| TW438596B (en) * | 1999-02-26 | 2001-06-07 | Inst Of Nuclear Energy Res Roc | Preparation of a new technetium-99m radiopharmaceutical kit for dopamine transporter imaging |
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Non-Patent Citations (3)
| Title |
|---|
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| 巴胺转运蛋白显像剂99TCM-TRODAT-1临床前药理研究 方平等，中华核医学杂志，第21卷第3期 2001 * |
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