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, based on volume:
1-30% PEG-300, 1-20% propylene glycol, 1-10% polyvinylpyrrolidone, and 0-10% Laurocapram.
2. The pharmaceutical agent of claim 1 , wherein the PEG-300 is 10-30% PEG-300 and wherein the aqueous pharmaceutical carrier further comprises 5-20% polyvinyl alcohol based on volume.
3. The pharmaceutical agent of claim 1 , wherein R 1 is a lower alkyl group from 1 to 6 carbon atoms, and R 2 is a primary, secondary, or tertiary amine, or an alkoxy group.
4. 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.
5. The pharmaceutical agent of claim 4 , wherein the PEG-300 is 10-30% PEG-300 and wherein the aqueous pharmaceutical carrier further comprises 5-20% polyvinyl alcohol based on volume.
6. The pharmaceutical agent of claim 4 , wherein R 4 and R 5 taken together form a heterocyclic ring or a substituted heterocyclic ring structure.
7. The pharmaceutical agent of claim 6 , wherein R 4 and R 5 taken together form piperidine, piperazine, morpholine, or an alkyl or alkoxyl substituted piperidine, piperazine, or morpholine.
8. The pharmaceutical agent of claim 6 where Formula I is:
9. 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.
10. The pharmaceutical agent of claim 9 , wherein the anion is a chloride.
11. 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 field 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, based on volume:
10-30% PEG-300 and 5-20% polyvinyl alcohol;
detecting the agent by applying a light source tuned to the spectral excitation characteristics of the agent; and observing a subject through an optical filter tuned to the spectral emission characteristics of the agent.
12. The method of claim 11 , wherein the detecting is effected by fluorescence microscopy, laser-confocal microscopy, cross-polarization microscopy, autoradiography, or a combination thereof.
13. The method of claim 11 , wherein R 1 is a lower alkyl group from 1 to 6 carbon atoms, R 2 is a primary, secondary, or tertiary amine, or an alkoxy group.
14. The method of claim 11 , 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.
15. The method of claim 14 , wherein the aqueous pharmaceutical carrier further comprises, based on volume:
1-20% propylene glycol, 1-10% polyvinyl pyrrolidone, and 0-10% Laurocapram.
16. The method of claim 14 , wherein R 4 and R 5 taken together form a heterocyclic ring or a substituted heterocyclic ring structure.
17. The method of claim 16 , wherein R 4 and R 5 taken together form piperidine, piperazine, morpholine, or an alkyl or alkoxyl substituted piperidine, piperazine, or morpholine.
18. The method of claim 17 , where Formula I is:
19. The method of claim 11 , wherein Formula I is a salt further comprising an anion and said anion is a halide, a polyatomic anion, or a basic active compound.
20. The method of claim 19 , wherein the anion is a chloride.
21. The method of claim 11 , further comprising determining the presence of myelin based on spectral excitation of the agent.
22. A kit for providing 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;
an aqueous pharmaceutical carrier comprising, based on volume: 1-30% PEG-300, 1-20% propylene glycol, 1-10% polyvinylpyrrolidone, and 0-10% Laurocapram; and
a co-solvent, surfactant, buffer solution, stabilizer, preservative, or any combination thereof.
23. The kit of claim 22 , wherein the PEG-300 is 10-30% PEG-300 and wherein the aqueous pharmaceutical carrier further comprises 5-20% polyvinyl alcohol based on volume.
24. The kit of claim 22 , wherein the pharmaceutical carrier further comprises a percutaneous enhancer, wherein the percutaneous enhancer comprises Laurocapram.