TOPICAL APPLICATION OF NERVE LABELING DYES FOR IMAGE-GUIDED SURGERY
The present invention relates to a topical agent that binds specifically to myelin basic protein and its method of use and determining myelination in the subject by detecting the agent present in the subject. A kit containing the agent or its derivatives for use in detecting myelin basic protein is also provided.
1 . A topical administered pharmaceutical agent comprising a compound of Formula I or a salt thereof, wherein Formula I is:
wherein R 1 is an alkyl group, R 2 is an electron donating group and R 3 is an electron withdrawing group; and
an aqueous pharmaceutical carrier comprising;
at least two solvents selected from PEG-300, propylene glycol, polyvinyl pyrrolidone, polyvinyl alcohol, carbapol, and Laurocapram.
2 . The pharmaceutical agent of claim 1 where, the aqueous pharmaceutical carrier comprises, based on volume;
1-30% PEG-300, 1-20% propylene glycol, 1-10% polyvinyl pyrrolidone, and 0-10% Laurocapram.
3 . The pharmaceutical agent of claim 1 where, the aqueous pharmaceutical carrier comprises based on volume; 10-30% PEG-300 and 5-20% Polyvinyl alcohol.
4 . The pharmaceutical agent of claim 1 wherein R 1 is a lower alkyl groups from 1 to 6 carbon atoms, R 2 is a primary, secondary, or tertiary amine, or an alkoxy group.
5 . The pharmaceutical agent of claim 1 wherein Formula I is:
where R 1 is an alkyl group, R 2 is an electron donating group, and R 4 and R 5 are independently hydrogen, alkyl, substituted alkyl, amine, substituted amine, or taken together form a heterocyclic ring or substituted heterocyclic ring structure.
6 . The pharmaceutical agent of claim 5 where, the aqueous pharmaceutical carrier comprises, based on volume;
1-30% PEG-300, 1-20% propylene glycol, 1-10% polyvinyl pyrrolidone, and 0-10% Laurocapram.
7 . The pharmaceutical agent of claim 5 where, the aqueous pharmaceutical carrier comprises based on volume; 10-30% PEG-300 and 5-20% polyvinyl alcohol.
8 . The pharmaceutical agent of claim 5 , wherein R 4 and R 5 taken together form a heterocyclic ring or a substituted heterocyclic ring.
9 . The pharmaceutical agent of claim 8 , wherein R 4 and R 5 taken together form piperidine, piperazine, morpholine, an alkyl or alkoxyl substituted piperidine, piperazine, or morpholine.
10 . The pharmaceutical agent of claim 8 where Formula I is:
11 . The pharmaceutical agent of claim 1 wherein Formula I is a salt further comprising an anion and said anion is a halide, a polyatomic anion, or a basic active compound.
12 . The agent of claim 11 wherein the anion is a chloride.
13 . A method of imaging myelin basic protein in an open or minimally invasive surgical field by topical administration of a pharmaceutical agent comprising the steps of:
contacting the surgical site with a pharmaceutical agent, said agent comprising a compound of Formula I or a salt thereof, wherein Formula I is:
wherein R 1 is an alkyl group, R 2 is an electron donating group and R 3 is an electron withdrawing group; and
an aqueous pharmaceutical carrier comprising;
at least two solvents selected from PEG-300, propylene glycol, polyvinyl pyrrolidone, polyvinyl alcohol, carbapol, and Laurocapram; and
detecting the agent by applying a light source tuned to the spectral excitation characteristics of the agent, and observing the subject through an optical filter tuned to the spectral emission characteristics of the agent; and
optionally determining the presence of myelin based on spectral excitation of the agent.
14 . The method of claim 13 wherein the detecting is effected by fluorescence microscopy, laser-confocal microscopy, cross-polarization microscopy, autoradiography, or a combination thereof.
15 . The method of claim 13 where, the aqueous pharmaceutical carrier comprises, based on volume;
1-30% PEG-300, 1-20% propylene glycol, 1-10% polyvinyl pyrrolidone, and 0-10% Laurocapram.
16 . The method of claim 13 where, the aqueous pharmaceutical carrier comprises based on volume; 10-30% PEG-300 and 5-20% polyvinyl alcohol.
17 . The method of claim 13 wherein R 1 is a lower alkyl groups from 1 to 6 carbon atoms, R 2 is a primary, secondary, or tertiary amine, or an alkoxy group.
18 . The method of claim 13 wherein Formula I is:
where R 1 is an alkyl group, R 2 is an electron donating group, and R 4 and R 5 are independently hydrogen, alkyl, substituted alkyl, amine, substituted amine, or taken together form a heterocyclic ring or substituted heterocyclic ring structure.
19 . The method of claim 18 where, the aqueous pharmaceutical carrier comprises, based on volume;
1-30% PEG-300, 1-20% propylene glycol, 1-10% polyvinyl pyrrolidone, and 0-10% Laurocapram.
20 . The method of claim 18 where, the aqueous pharmaceutical carrier comprises based on volume; 10-30% PEG-300 and 5-20% polyvinyl alcohol.