Title of Invention

"A PROCESS FOR PREPARATION OF TECHNETIUM-4-FLUOROQUINOLONE METALLIC COMPLEX"

Abstract

This invention provides a process for preparation of Technetium-4-f1uroquniolone metallic complex which has application as imaging agent for detection and localisation of Infectious lesion in any part of the body. This complex is especially useful in differentiating between infectious lesion and inflammation for which no other mode of detection is known to be available. The localisation is made possible with just one Imaging/scanning thereby obviating the need for repeated imaging (as required in X-ray) of different parts of the body to localise the disease. The imaging agent enables detection of the disease at very early stages thereby enabling effective control of the disease right at the initial stages. The technetium-4-f1uroquinolone metallic complex of the present invention is not known in the prior art.

Full Text

FIELD OF INVENTION The present invention relates to a process for preparation of Technetiums-fluoroquinolone metallic complex for use as an infection imaging agent for detection and localisation of infectious lesions in male and female, in any part of the body, particularly to differentiate between inflamation and infectious lesion. BACKGROUND OF THE INVENTION Infectious diseases cause more deaths than the deaths caused by cancer or coronary attery disease. The infectious diseases are much more prevalent in the third world countries like India, due to poor civic amenities and malnutrition. Infectious lesion can develop in any organ of the body and if not detected, followed by proper treatment may lead to death. Deaths due to the infectious diseases can be curtailed to a great extent if detected and located at an early stage of development. Some of the methods known in the art, for detection of infectious lesion are by culturing or biopsy or microbiological analysis of the samples drawn from the patient. The main drawback of above methods for detection of infectious lesion is that they are sensitive at a later stage of the development of infection, which in turn makes the treatment not only difficult but also less effective. Another disadvantage of the above method is that the detection of infectious lesion by way of culturing of the samples is time consuming. Still another disadvantage of the above method is that the biopsy is invasive in nature Further disadvantage of the method of detection by biopsy is that it is possible only after the infectious lesion has been localized, hence this method is dependent or. the localization of the suspected infectious lesion. Further limitation of the biopsy method is that the finding of the site of the infectious lesion is difficult. The limitation of the method of detection by way of culture of sputum or blood is that such tests are limited for location of tuberculosis lesion in the lung and bone region. Still another limitation of these known methods is that the method of detection by culturing of sputum or blood is suitable only for detection but not for specific localization of the infectious lesion. The other methods known in the art for detection of infectious lesion include radiographic techniques, like X-ray, CT scan, MRI scan. The major limitation of these radiographic techniques is that these techniques rely on anatomical changes at the site of the infectious lesion which are detectable at a later stage or at the advanced stage of infection. This in turn has the inherent disadvantage of making the early detection and localization not only difficult but impossible. Still another limitation of these radiographic techniques is that such methods are suitable only for detection and localization of the suspected infectious lesion only in the region where the radiographic test is performed. Such methods will not reveal any information about the infectious lesion in other region where such test is not performed. The localisation of infectious lesion would require radiographic test at each suspected site of infection, which generally result in the whole body scan by performing X-ray, CT scan or MRI of every suspected part of the body. Yet another limitation of these radiographic techniques is that they can not differentiate between infectious lesion and inflammation. The major disadvantage of performing repeated imaging, particularly by X-ray and CT scanning is that the patient is exposed to harmful X-rays, which have their known inherent disadvantages. The another major disadvantage of the above imaging methods is that such methods are very expensive, particularly CT scanning and MRI scanning. NEED OF THE INVENTION Therefore, there is a need for a process which provides an imaging agent which can detect and localise infectious lesion at an early stage of development, which can differentiate inflammation and infection and which can localise infection in any part of body without exposing the patient to repeated imaging. OBJECTS OF THE INVENTION The main object of the present invention is to propose a process for preparation of Technetium-4-fluroquinolone metallic complex which can detect and localise infectious lesion. Another object of the present invention is to propose a process for preparation of Technetium-4-fluroquinolone metallic complex which can differentiate between inflammation and infectious lesion. Yet another object of the present invention is to propose a process for preparation of Technetium-4-fluroquinolone metallic complex which can detect and localise infectious lesion in any part of the body, in one scanning/imaging thereby obviating the need for repeated imaging of the patient Still another object of the present invention is to propose a process for preparation of Technetium-4-fluroquinolone metallic c omolcx which can detect and localise infectious lesion at an early stage of the development of disease, thereby making it possible to treat the disease at an early stage which can in turn be more effective in controlling the disease Further object of the present invention is to propose a process for preparation of Technetium-4-fluroquinolone metallic complex which is easy to be performed for detection and localisation of the infectious lesion. Still further object of the present invention is to propose a process for preparation of Technetiuin-4-fluroquinoIone metallic complex which can be used to assess the treatment response by repeating the imaging after required time interval Yet further object of the present invention is to propose a process for preparation of Technetium-4-fluroquinolone metallic complex which does not involve hazardous acidic medium for its preparation. Yet another object of the present invention is to propose a process for preparation of Technetium-4-fluroquinolone metallic complex with high purity and better yield. STATEMENT OF INVENTION According to this invention, there is provided a process for preparation of Technetiums-fluoroquinolone metallic complex used in the detection and localization of infectious lesion which comprises: (a) dissolving 4-fluroquinolone in water has been prepurged with an inert gas; (b) complexing 4-fluroquinolone with technetium by adding technetium to the reaction mixture of 4-lluroquinolone as prepared by step (a) and a chemical reducing agent to produce the desired Technetium-4-fluroquinolone metallic complex. The process of the present invention involves preparation of 4-fluroquinolone solution by dissolving 500 to 700µ, moles in 1 ml of water for injection which was prepurged with an inert gas preferably nitrogen. The solution thus prepared is purged again with nitrogen. Stannous tartarate solution is separately purged with nitrogen and then added to the solution of 4-fluroquinolone in water. To this solution, technetium is added. Alternatively 4-fluroquinolone and stannous tartarate can simultaneously be added to the technetium. This reaction is carried out at 20° to 35°C with gentle swirling. Technetium 4-floroquinolone metallic complex of 95% purity is obtained. DESCRIPTION OF THE INVENTION According to the present invention, the process for preparation of technetium 4- fluroquinolone metallic complex comprises of following steps:- a) Preparartion of 4-fluroquinolone Solution Water for injection is taken in a vial and sealed and then purged with an inert gas preferably nitrogen, at temperature of 20°C to 35°C. For one ml of this solution, 300 to 900 µ moles, preferably 500 to 700µ moles of 4-fluroquinolone is dissolved with shaking. b) Complexation of 4-fluroquinolone with Technetium Stannous tartarate is separately taken in a vial containing water purged with nitrogen, taking about 2 mg of stannous tartarate for 1 ml of purged distilled water. This aqueous solution of stannous tartarate is purged again with nitrogen. About 1.5 µmoles of this purged stannous tartarate solution is then added to 4-fluroquinolone solution prepared by step (a) above. Technetium is eluted from molybdenum generator in normal saline. Then 0.64x10-10 moles of technetium ether cold of radioactive are added with gentle swirling to the reaction mixture of stannous tartarate and 4-fluroquinolone prepared above. The reaction mixture is allowed to react at 20°C to 35°C for about 15 minutes leading to the formation of the complex of the present invention. The invention will now be illustrated with a working example is intended to be illustrative example and is not intended to be taken restrictively to imply any limitation on the scope of the present invention. WORKING EXAMPLE 600µ moles of 4-fluroquinolone were dissolved in 1 ml of water for injection, which has been purged with nitrogen gas. The resulting solution was again purged with nitrogen. To the solution thus obtained, 1.5 µ moles of stannous tartarate was added. The 0.64xl0-10 moles of Technetium in saline were added to it and the reacting mass was allowed to react for 15 minutes. The resulted complex was subjected to check of purity and yield It was observed that the complex of the present invention is about 95% pure with about 95% complex formation. Further the complex was subjected to stability test to find out the shelf life, which was found to be > 90% in about 24 hours when incubated at about 37°C temperature. CLAIM 1 A process for preparation of Technetium-4-fluoroquinolone metallic complex used in the detection and localization of infectious lesion which comprises: (a) dissolving 4-fluroquinolone in water which has been prepurged with an inert gas such as herein described; (b) complexing 4-fluroquinolone with technetium by adding technetium to the reaction mixture of 4-fluroquinolone as prepared by step (a) and a chemical reducing agent such as herein described to produce the desired Technetium-4-fluroquinolone metallic complex. 2 A process as claimed in claim 1 wherein said inert gas is nitrogen. 3 A process as claimed in claims 1 and 2 wherein 4-fluroquinolone is dissolved in water in the ratio of 300 to 900 µ moles preferably 500 to 700µ. moles of 4-fluroquinolone to ever}' 1 ml of water. 4 A process as claimed in claims 1 to 3 wherein said chemical reducing agent is preferably stannous tartarate in form of solution having 2 mg of said agent to each 1 ml of the prepurged distilled water, 1.5µ moles of the said solution being added to each 1ml of the products of step (a). 5. A process as claimed in claims 1 to 4 wherein 0.64xl0-10 moles of technetium are added for each 1ml of products of step (a) for said complexing. 6 A process as claimed in claims 1 to 5 wherein said complexing is carried out for about 15 min. 7 A process as claimed in claims 1 to 5 wherein said complexing is carried out at 20 to 35°C. 8 A process for preparation of Technitium-4-fluoroquinolone metallic complex substantially as herein described and illustrated in the example.

Documents:

499-del-2001-abstract.pdf

499-del-2001-claims cancelled.pdf

499-del-2001-claims.pdf

499-del-2001-complete specification (granted).pdf

499-del-2001-correspondence-others.pdf

499-del-2001-correspondence-po.pdf

499-del-2001-description (complete).pdf

499-del-2001-form-1.pdf

499-del-2001-form-2.pdf

499-del-2001-form-3.pdf

499-del-2001-form-4.pdf

499-del-2001-gpa.pdf