CN100382847C - Ligand compound for image diagnosis and its preparing method and compound for image diagnosis and its intermediate preparation - Google Patents
Ligand compound for image diagnosis and its preparing method and compound for image diagnosis and its intermediate preparation Download PDFInfo
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Abstract
The present invention relates to a ligand compound which can be used for imaging diagnosis, a preparation method thereof, an intermediate compound for preparing the ligand compound, and a compound for imaging diagnosis, and the compound for imaging diagnosis is formed from the ligand compound disclosed in formula (I) in the specification. In the formula (I), R1 can be in a deoxidated pentose structure, a deoxidated hexose structure or a deoxidated polyose structure substituted by pentose, hexose, polyose, a sulfhydryl group, an amino group, an amine group, cyano group, a carboxyl group or an ester group which are usual; R2 and R3 can also be respectively H besides respectively being the saccharide and/or substituted saccharide. The preparation method of the compound has the advantages of simplicity and low cost. The compound matched with a coordination compound frequently used and formed from a tracer element for imaging diagnosis has an ideal image display effect, the marked biological behavior of the compound is similar to that of DG and that of F<18>-FDG, but the cost for image display is greatly reduced. The ligand compound which is a medicinal compound for molecule image inspection has the advantages of no wound, real time, living organism, low price, convenience and accuracy. The ligand compound is favorable to the popularization and the application of the early clinical diagnosis of tumor diseases.
Description
Technical field
What the application related to is a kind of ligand chemical compound, this preparation process of mixture that is used for diagnostic imaging, and this image diagnosis chemical compound and be used for the midbody compound that it prepares this ligand chemical compound accordingly.
Background technology
Carbohydrate metabolism is active to be an important metabolic characteristics of tumor cell.One of metabolic main feature of malignant cell is that its glucose uptake increases and the anerobic glycolysis effect strengthens.Be called as " century molecule " glucalogue 18 fluorodeoxyglucose (
18F-FDG) can be absorbed by tumor cell, in the tumor tissues
18The F-FDG level distribution is apparently higher than tumor tissues normal structure and benign lesion on every side, be used to clinically to the Differential Diagnosis of innocent and malignant tumour focus, pernicious focus by stages with classification, differentiate the recurrence of tumor focus and variation due to the treatment back, the curative effect of various anticancer therapies monitored and the prognosis judgement of the state of an illness etc. that clinical meaning is great.But
18F-FDG PET (positron computer layer video picture) needs to produce with cyclotron, the cost height, and the half-life short (only 110 minutes), used in addition nuclear medicine PET imager costs an arm and a leg, and these have all limited its penetration and promotion in basic medical unit is clinical and have used.
In addition,
99mTc has ideal nuclear physics performance, long half time (6.02 hours), and the gamma-rays of emission 40KeV,
99mThe Tc generator obtains easily, thereby is optimal γ video picture radionuclide.With
99mTc labelled glucose analog will have the important clinical meaning, and be used widely.Yang DJ was at Radiology 2003 in 2003; Among the 226:465-473, once reported synthetic ethylenedicysteine (EC)-D-glucose (DG), and used
99mThe Tc labelling; Right
99mThe distribution research prompting of Tc-ECDG: tumor/brain and tumor/muscle ratio are higher than
18F-FDG,
99mThe Tc-ECDG video picture can clear demonstration malignant tumor focus.Therefore
99mTc-ECDG with
18F-FDG all can be absorbed by malignant tumor and as malignant tumor functional molecular developer.But because
99mThe distribution of Tc-ECDG shows that its tumor and tumor/lung ratio less than 1.0, are lower than
18F-FDG, thereby
99mTc-ECDG also is not ideal
99mTc labelling DG developer, with
18F-FDG has big gap.Therefore, it is low to study a kind of tumor uptake height, tumor/background height, bio distribution and video picture ideal and cost
99mThe DG derivant of Tc labelling is necessary.
Summary of the invention
In view of the foregoing, the present invention's purpose at first is a kind of ligand chemical compound and corresponding image diagnosis chemical compound that is used for diagnostic imaging.Further aim of the present invention also comprises respectively and prepares the midbody compound that this is used for the ligand chemical compound of diagnostic imaging with being provided for, and provides a kind of said this to be used for the preparation method of the ligand chemical compound of diagnostic imaging.
The present invention is used for the ligand chemical compound of diagnostic imaging, is the acyl group carbohydrate derivative of diethylenetriamine pentaacetic acid, and structure is shown in general formula (I).
In general formula (I) structure, R
1Can be pentose, hexose, polysaccharide, or the deoxidation pentose, deoxidation hexose, the deoxidation polysaccharide structures that replace by sulfydryl, amino, amido, cyano group, carboxyl, ester group etc.For example glucose, allose, mannose, galactose, 6-sulfydryl glucose, 2-glucosamine ... etc. common C
6Sugar or replace glycan molecule accordingly also can be as the amino ribose of common fructose, ribose, 6-sulfydryl ribose, 2-... Deng C
5Glycan molecule, or disaccharidase such as sucrose, maltose, lactose, SKGM or polysaccharide and sulfydryl, amino, amido, cyano group, carboxyl, ester group etc. replace the polysaccharide of form, as ganoderan, wood polysaccharose, aminopolysaccharide etc.
R in general formula (I) structure
2, R
3Except that can also can be above-mentioned pentose, hexose, polysaccharide respectively and replacing accordingly deoxidation pentose, hexose or the polysaccharide molecule, can also distinguish or simultaneously for H.Work as R
1, R
2And/or R
3During for glycan molecules such as above-mentioned pentose, hexose, polysaccharide, each the CO-R key in the formula (I) should be corresponding ester bond; R
1, R
2And/or R
3During for above-mentioned replacement glycan molecule, then each the CO-R key in the formula then is corresponding acyl-heterodesmic.
Experimental result shows, in the chemical compound of above-mentioned general formula (I), particularly with R
1Be C
6The osamine structure, R
2And R
3For the effect of the chemical compound of H even more ideal.The R shown in the formula (II) for example
1Be 2-glucosamine, R
2, R
3Can be used as the chemical compound of one of them instantiation for the structure of H.
Acyl group carbohydrate derivative and the formed coordination compound of tracer element by the diethylenetriamine pentaacetic acid shown in the general formula (I); can be used as the video picture chemical compound that is used for diagnostic imaging; and have an ideal diagnostic imaging imaging results, biological behaviour behind its labelling and above-mentioned DG,
18F-FDG etc. are similar.Said tracer element can selected in existing report and/or multiple metal that uses or the nonmetalloid at present, as can
99mTc,
188Re,
186Re, Rh, Ru, I, Gd
3+, Mn
2+, Cr
3+, Fe
3+, Fe
2+, Co
2+, Ni
2+, Eu, Dy, Tm selects for use in the elements such as Yb, wherein with
99mTc,
188Re is preferred.
With above-mentioned formula (II) chemical compound with
99The video picture experimental result that the coordination compound that Tc forms carries out is as follows:
DTPA-DG's
99mThe breast carcinoma MCF-7 nude mice video picture experiment of Tc coordination compound
Get 3 of breast carcinoma MCF-7 nude mices, it is fixing to lie on the back, and injects 3.7MBq/0.1ml through the tail vein, dynamic acquisition 60 frames (1 frame/2 minute); Carry out static state collection respectively at 1h, 2h, 3h, 4h, 6h, 24h behind the tracer injection, observe
99mTc-DTPA-DG is in the dense poly-situation of tumor kitchen range, with the radiocounting ratio (T/B) of ROI technique computes focus and strong side thigh correspondence position.
30min tumor kitchen range is video picture after the intravenous injection, the kidney shadow as seen, the bladder radioactivity increases gradually, all the other organs such as brain, lung, small intestinal, muscle do not have obvious increased radioactivity and increase, and do not see that thyroid, stomach develop.Tumor kitchen range clear display after 1 hour, its radioactivity of perusal is higher than offside.The T/B ratio that records 1h, 2h, 3h, 4h, 6h with the ROI technology is respectively 3.5,3.8,4.9,5.1,4.3.
99mThe video picture of Tc-DTPA-DG tumor animal can clear demonstration tumor kitchen range.
Above-mentioned experimental result shows, its tumor uptake height, and tumor/background height, bio distribution and video picture obviously are better than
99mTc-ECDG.With
188The video picture result of the test that Re carries out similarly.
To being used for the preparation of the ligand chemical compound of diagnostic imaging shown in the above-mentioned formula (I), can be raw material by diethylenetriamine pentaacetic acid (IV) by existing report, under the effect of dihalide sulfoxide, obtain important intermediate compound earlier suc as formula the two acid anhydride structures of carboxylic acid halides shown in (III), and then with above-mentioned C
6Sugar, C
5Sugar, C
6Osamine or C
5Osamine reaction obtains target compound (I), course of reaction as shown in the formula:
X in the formula can adopt Cl, the Br etc. in the halogen commonly used; R
1, R
2And R
3Be respectively the sugar or the sugar replaced chemical compound of above-mentioned scope.
In above-mentioned course of reaction, formula (IV) chemical compound during the adjustment reaction is raw materials used and the consumption mol ratio of sugar or osamine etc. can obtain multi-form formula (I) product.For example, during molar ratio reactions such as employing, in a large number available or all be R
1Be sugar or osamine, R
2And R
3Product (I) for H; When adopting (IV) to be 1: 3 mol ratio, can obtain a large amount of R with sugar or osamine
1, R
2And R
3The product of sugar or osamine; When adopting 1: 2 mol ratio, the product that then obtains is R
1Be sugar or osamine, R
2And R
3The mixed structure (I) of difference H and/or sugar or osamine.The product of this mixed structure form and not obvious imaging results when influencing it and using, but as need and can also further separate this mix products, just separating difficulty is bigger.
The reaction condition of above-mentioned preparation process, generally can adopt:
1) stirs with the dihalo-sulfoxide (as the most frequently used SOCl
2) in-30 ℃～0 ℃ splash into diethylenetriamine pentaacetic acid (DTPA) (IV) in,-30 ℃～100 ℃ stirrings, and with reactant backflow 12～28 hours, decompression steamed superfluous dihalo-sulfoxide, get the two acid anhydride intermediate compounds (III) of carboxylic acid halides, can directly carry out the next step without separating.
2) in the two acid anhydrides of carboxylic acid halides that obtained in last step, add DMSO, pyridine and corresponding sugar or replace sugar (as the amino D-glucosamine salt of 2-hydrochlorate etc.), mixture stirred 24～48 hours in-50 ℃～196 ℃.Reacted reaction solution is with dialyzer or polydextran gel (G10; G15; Or G25) etc. method is carried out separation and purification, promptly obtains corresponding formula (I) structure product.
(3) the image diagnosis chemical compound (with the preparation
99mThe Tc-DTPA-DG coordination compound is an example):
Get 25mg DTPA-DG and be dissolved in the 0.2ml distilled water, add SnCl
22H
2The hydrochloric acid solution 0.1ml of O, regulator solution pH to 6.0 is with an amount of Na
99mTcO
4(or other tracer element or derivative solution) leacheate reacted 10 minutes at room temperature placement 30 minutes or boiling water bath more than 25 ℃.
Above-mentioned result of the test shows, above-mentioned formula (I) chemical compound of the present invention with
18The result of use of F-FDG is suitable, but with
99mVideo picture cost that Tc cooperates and expense but reduce significantly, not as good as above-mentioned
181/10 of F-FDG more helps its penetration and promotion in clinical and uses, for the early diagnosis of human tumor disease provides more inexpensive, convenient and effective instrument.
Below example by the specific embodiment again foregoing of the present invention is described in further detail.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following example.Do not breaking away under the above-mentioned technological thought situation of the present invention, various replacements or change according to ordinary skill knowledge and customary means are made include within the scope of the invention.
The specific embodiment
Embodiment 1
1) stirs down 10ml SOCl
2In-30 ℃ splash into 3.94g diethylenetriamine pentaacetic acid (DTPA) (IV) in, can at room temperature continue to stir 3 hours.Result of the test shows that this process carries out the result is not generally all shown significant adverse effect in-30 ℃～100 ℃ temperature ranges.Then reactant was refluxed 20 hours, decompression steams superfluous SOCl
2, intermediate compound (III) the pale yellow powder 3.76g of the two acid anhydrides of acyl chlorides, can not add separation and directly carry out the next step.
2) go on foot among the two acid anhydride 3.76g (0.010mol) of the acyl chlorides that obtains last, add 30ml DMSO, 5ml pyridine and 2.85g (0.0132mol) 2-amino-D-glucosamine salt hydrochlorate, mixture generally can stir 24 hours (operative temperature of this process can allow for 20 ℃～150 ℃) under room temperature, get transparent brown solution.This solution separates purification through dialyzer or polydextran gel (G10) etc., gets DTPA and the D-glucamine condensation substance (DTPA-DG) shown in the formula (II).
MS(m/e)：555(M
+)，394，351
1H-NMR(ppm)：δ12.2(4H，b)；δ8.1(b)；δ5.2(1H)；δ4.6(1H，)；δ3.8(2H)；δ3.7(2H)；δ3.6(1H)；δ3.5(10H)；δ3.1(4H)；δ2.9(4H)；δ2.5(4H)
3) preparation
99mThe Tc-DTPA-DG coordination compound:
Get 25mg DTPA-DG and be dissolved in the 0.2ml distilled water, add SnCl
22H
2The hydrochloric acid solution 0.1ml of O, regulator solution pH to 6.0 is with an amount of Na
99mTcO
4Leacheate reacted 10 minutes at room temperature placement 30 minutes or boiling water bath more than 25 ℃.
Measure with the TLC method
99mThe radiochemical purity of Tc coordination compound.TLC carries out on chromatographic paper of 10cm Xinhua.1-2 μ L sample is placed the starting point of chromatography strip, launch with 0.9%NaCl and acetone soln respectively, after the expansion, natural airing in the air is divided into 11 sections, measures every section radioactivity and counts.In acetone expansion system
99mTc-DTPA-DG and reductive hydrolysis
99mTcO
2Rf value be 0～0.1, free
99mTcO
4 -Rf value be 0.9～1.0; In 0.9%NaCl expansion system
99mTc-DTPA-DG and free
99mTcO
4 -Rf value be 0.9～1.0, reductive hydrolysis
99mTcO
2Rf value be 0～0.1.
99mPutting of Tc-DTPA-DG is pure to reach 99.2%.
Label
99mTc-DTPA-DG is anti-putting 6 hours in air at room temperature, and radiochemicsl purity still reaches 98.6%, shown that it has stability preferably in air.
4)
99mThe bio distribution test of Tc-DTPA-DG coordination compound:
With body weight 18-22 gram Kunming mouse is the experimental animal grouping, presses 3.7MBq/0.1ml dosage through tail vein injection
99mThe Tc-DTPA-DG coordination compound was injected back 10 minutes and 1,2,4,8,24 hour sacrificed by decapitation mice, got blood and organ-tissue is weighed, and surveyed its radiocounting, the percentage injection measurement rate (%ID/g) of extremely every gram tissue.The result is as shown in table 1.
99mTc-DTPA-DG removes soon in body, and the kidney picked-up is higher, and the intestinal radioactivity is low, and this radioactive indicator mainly enters bladder by kidney with the urine form.Thyroid stomach function regulating increased radioactivity is low, and radiopharmaceutical is stable in vivo, and is free
99mTcO
4Form few.
Table 1.
99mTc-DTPA-DG normal mouse internal organs of the body bio distribution (x ± s) (%ID/g)
| Organ | 10 minutes | 1 hour | 2 hours | 4 hours | 8 hours | 24 hours |
| Blood | 11.73±0.92 | 205±0.75 | 0.66±0.17 | 0.48±0.11 | 0.51±0.08 | 0.16±0.02 |
| The heart | 5.13±0.62 | 1.03±0.29 | 0.29±0.03 | 0.31±0.10 | 0.25±0.04 | 0.15±0.03 |
| Lung | 9.41±2.35 | 1.79±0.34 | 0.67±0.07 | 0.41±0.12 | 0.34±0.16 | 0.19±0.04 |
| Liver | 5.36±0.95 | 2.79±0.33 | 2.73±1.01 | 1.64±0.28 | 1.4±0.48 | 0.44±0.16 |
| Spleen | 7.78±0.96 | 5.27±1.17 | 5.81±0.58 | 6.26±1.52 | 2.74±0.64 | 4.61±0.69 |
| Kidney | 29.75±9.06 | 11.07±4.48 | 4.41±0.94 | 4.14±1.96 | 2.03±0.12 | 0.43±0.06 |
| Stomach | 6.17±3.56 | 2.37±2.30 | 1.74±0.81 | 0.39±0.08 | 0.48±0.15 | 0.28±0.13 |
| Small intestinal | 3.60±1.37 | 1.536±1.15 | 1.29±1.03 | 0.29±0.12 | 0.24±0.03 | 0.08±0.03 |
| Muscle | 4.47±2.00 | 1.23±0.73 | 0.42±0.16 | 0.36±0.22 | 0.36±0.18 | 0.08±0.01 |
| Brain | 0.53±0.09 | 0.23±0.11 | 0.09±0.02 | 0.08±0.02 | 0.06±0.01 | 0.05±0.01 |
5) DTPA-DG
99mThe distribution of Tc coordination compound in breast carcinoma MCF-7 nude mice biology
With the female nude mice grouping of breast carcinoma MCF-7, all by the dosage of 3.7MBq/0.1ml through tail vein injection
99mTc-DTPA-DG, the injection back is respectively at 10min, 1h, 2h, 4h, 8h, 24h sacrificed by decapitation nude mice, get histoorgans such as blood, the heart, lung, liver,spleen,kidney, stomach, small intestinal, muscle, tumor, weigh and survey its radiocounting, calculate every gram and organize percentage injection dose rate (%ID/g), calculate organ/blood ratio and tumor/organ (T/NT) ratio.The result is as shown in table 2.
Table 2
99mDistribute in the Tc-DTPA-DG breast carcinoma MCF-7 nude mouse
%ID/g
Annotate: in expanding number is organ/blood ratio
Table 2 result demonstration, behind the injection 10min,
99mTc-DTPA-DG is higher in the kidney radioactivity, and stomach does not have obvious increased radioactivity, and the intestinal radioactivity is low, and radioactive indicator mainly enters bladder through renal excretion through urine.Increased radioactivity is low in the cerebral tissue.The every gram tumor tissues of 1h, 2h percentage injection dose rate is respectively 3.10 ± 0.87,2.10 ± 0.02, and 8h is 1.69 ± 0.03.Tumor ratio 1h reaches 1.29 ± 0.26, and 2h reaches 3.13 ± 0.63; Tumor/muscle ratio 1h reaches 2.63 ± 0.53, and 2h reaches 5.01 ± 1.02, and 1h～8h tumor ratio, tumor/muscle ratio are all higher, than aforementioned Radiology2003; The 226:465-473 bibliographical information
99mThe Tc-ECDG height.
Embodiment 2
In the two acid anhydrides (0.010mol) of the acyl chlorides that obtains by embodiment 1 mode, add 40ml DMSO, 8ml pyridine and 7.55g (0.035mol) 2-amino-D-glucosamine salt hydrochlorate, mixture gets transparent brown solution in 20 ℃～140 ℃ stirrings 40 hours.This solution separates purification through dialyzer or polydextran gel (G15) etc., gets R in formula (I) structure
1, R
2And R
3Be the product (DTPA-3DG) of D-glucamine-2.
Be equipped with gained DTPA-3DG product
188The method of Re-DTPA-3DG coordination compound is with reference to embodiment 1.
Embodiment 3
In the two acid anhydrides (0.010mol) of the acyl chlorides that obtains by embodiment 1 mode, add 30ml DMSO, 6ml pyridine and 2.35g (0.012mol) 2-sulfydryl-D-glucose, mixture gets brown solution in-10 ℃～120 ℃ stirrings 40 hours.This solution separates purification through dialyzer or polydextran gel (G10) etc., gets R
1Be 2-sulfydryl-D-glucose, R
2And R
3Be formula (1) the structure product of H.
Embodiment 4
In the two acid anhydrides (0.010mol) of the acyl chlorides that obtains by embodiment 1 mode, add 30ml DMSO, the hydrochlorate of the amino ribose of 5ml pyridine and 2.23g (0.012mol) 2-, mixture gets transparent brown solution in 20 ℃～130 ℃ stirrings 24 hours.This solution separates purification through dialyzer or polydextran gel (G10) etc., gets R
1Be the amino ribose of 2-, R
2And R
3Be formula (I) the structure product of H.
Embodiment 5
In the two acid anhydrides (0.010mol) of the acyl chlorides that obtains by embodiment 1 mode, add 30ml DMSO, the hydrochlorate of 5ml pyridine and 2.80g (0.013mol) 3-amino-D-glucose, mixture gets transparent brown solution in 20 ℃～110 ℃ stirrings 26 hours.This solution separates purification through dialyzer or polydextran gel (G10) etc., gets R
1Be 3-amino-D-glucose, R
2And R
3Be formula (I) the structure product of H.
Embodiment 6
In the two acid anhydrides (0.010mol) of the acyl chlorides that obtains by embodiment 1 mode, add 30ml DMSO, 5ml pyridine and 2.32g (0.013mol) D-glucose, mixture gets transparent brown solution in 20 ℃～150 ℃ stirrings 28 hours.This solution separates purification through dialyzer or polydextran gel (G10) etc., gets R
1Be D-glucose, R
2And R
3Be formula (I) the structure product of H.
Embodiment 7
In the two acid anhydrides (0.010mol) of the acyl chlorides that obtains by embodiment 1 mode, add 50ml DMSO, 5ml pyridine and sucrose (0.014mol), mixture gets brown solution in 30 ℃～160 ℃ stirrings 40 hours.This solution separates purification through dialyzer or polydextran gel (G15) etc., gets R
1Be sucrose, R
2And R
3Be formula (I) the structure product of H.
Embodiment 8
In the two acid anhydrides (0.010mol) of the acyl chlorides that obtains by embodiment 1 mode, add 50ml DMSO, 5ml pyridine and lactose (0.013mol), mixture gets transparent brown solution in 20 ℃～185 ℃ stirrings 48 hours.This solution separates purification through dialyzer or polydextran gel (G15) etc., gets R
1Be lactose, R
2And R
3Be formula (I) the structure product of H.
Claims (8)
1. the ligand chemical compound that is used for diagnostic imaging is the aminosaccharide derivant of diethylenetriamine pentaacetic acid, and structure is shown in general formula (I)
R in formula (I) structure
1Be 2-glucosamine, R
2, R
3Be respectively OH, or pentose, hexose, polysaccharide, and deoxidation pentose, deoxidation hexose, the deoxidation polysaccharide structures of sulfydryl, amino, amido, cyano group, carboxyl or ester group replacement.
2. the ligand chemical compound that is used for diagnostic imaging as claimed in claim 1 is characterized in that said ligand chemical compound is the structure shown in the formula (II)
3. the chemical compound of image diagnosis is aminosaccharide derivant and the formed coordination compound of radioactive tracer element by the diethylenetriamine pentaacetic acid shown in the general formula as claimed in claim 1 (I).
4. the chemical compound of image diagnosis as claimed in claim 3, the aminosaccharide derivant that it is characterized in that said diethylenetriamine pentaacetic acid is the structure shown in the formula (II).
5. the chemical compound of image diagnosis as claimed in claim 3 is characterized in that said radioactive tracer element is
99mTc.
6. the chemical compound of image diagnosis as claimed in claim 3 is characterized in that said radioactive tracer element is
186Re.
7. be used to prepare the described precursor intermediate compound that is used for the ligand chemical compound of diagnostic imaging of claim 1, structure is suc as formula shown in (III), and the X in the formula (III) is a halogen
8. preparation is as being used for the method for the ligand chemical compound of diagnostic imaging as described in the claim 2, it is characterized in that with formula (III) chemical compound be the precursor intermediate compound, under the effect of dihalide sulfoxide, obtain this corresponding intermediate compound (III) earlier by diethylenetriamine pentaacetic acid (IV), then with etc. the 2-glucosamine reaction of mol ratio, obtain target compound (II), course of reaction is as follows, and the X in its Chinese style (III) is a halogen:
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0345723A2 (en) * | 1988-06-07 | 1989-12-13 | Nihon Medi-Physics Co., Ltd. | Diethylenetriamine pentaacetic acid derivatives |
| US5330743A (en) * | 1992-11-12 | 1994-07-19 | Magnetic Research, Inc. | Aminosaccharide contrast agents for magnetic resonance images |
| US5352431A (en) * | 1991-10-04 | 1994-10-04 | Nihon Medi-Physics Co., Ltd. | Low molecular weight polysaccharide complexes for X-ray imaging |
| CN1166987A (en) * | 1997-06-18 | 1997-12-10 | 武汉大学 | Magnetic resonance imaging contrast medium of paramagnetism metal compound containing D-galactose group |
| US5863518A (en) * | 1994-10-21 | 1999-01-26 | Nihon Medi-Physics Co., Ltd. | Diagnostic imaging agent with backbone with modified sugar chain end |
| US6677483B2 (en) * | 2001-01-26 | 2004-01-13 | Schering Ag | Process for the production of monoamides of DTPA |
-
2005
- 2005-02-05 CN CNB2005100203346A patent/CN100382847C/en not_active Expired - Fee Related
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0345723A2 (en) * | 1988-06-07 | 1989-12-13 | Nihon Medi-Physics Co., Ltd. | Diethylenetriamine pentaacetic acid derivatives |
| US5352431A (en) * | 1991-10-04 | 1994-10-04 | Nihon Medi-Physics Co., Ltd. | Low molecular weight polysaccharide complexes for X-ray imaging |
| US5330743A (en) * | 1992-11-12 | 1994-07-19 | Magnetic Research, Inc. | Aminosaccharide contrast agents for magnetic resonance images |
| US5863518A (en) * | 1994-10-21 | 1999-01-26 | Nihon Medi-Physics Co., Ltd. | Diagnostic imaging agent with backbone with modified sugar chain end |
| CN1166987A (en) * | 1997-06-18 | 1997-12-10 | 武汉大学 | Magnetic resonance imaging contrast medium of paramagnetism metal compound containing D-galactose group |
| US6677483B2 (en) * | 2001-01-26 | 2004-01-13 | Schering Ag | Process for the production of monoamides of DTPA |
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