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 pharmaceutical agent comprising:
a syringe;
a compound of Formula I or a salt thereof, wherein Formula I is:
wherein R1 is an alkyl group, R2 is an electron donating group and R3 is an electron withdrawing group; and
an aqueous pharmaceutical carrier, wherein the compound of Formula I and the aqueous pharmaceutical carrier are disposed in the syringe, wherein the aqueous pharmaceutical carrier comprises, based on volume:
1-30% PEG-300, 1-20% propylene glycol and 1-10% polyvinylpyrrolidone.
2. The pharmaceutical agent of claim 1 , wherein R1 is a lower alkyl group from 1 to 6 carbon atoms, and R2 is a primary, secondary, or tertiary amine, or an alkoxy group.
3. The pharmaceutical agent of claim 1 , wherein the aqueous pharmaceutical carrier comprises 5-30 percent cyclodextrin based on volume.
4. The pharmaceutical agent of claim 1 , wherein Formula I is:
where R1 is the alkyl group, R2 is the electron donating group, and R4 and R5 are independently hydrogen, alkyl, substituted alkyl, amine, substituted amine, or taken together form a heterocyclic ring or a substituted heterocyclic ring structure.
5. The pharmaceutical agent of claim 4 , wherein the aqueous pharmaceutical carrier comprises 5-30 percent cyclodextrin based on volume.
6. The pharmaceutical agent of claim 5 , wherein the cyclodextrin comprises 2-hydroxypropyl-β-cyclodextrin.
7. The pharmaceutical agent of claim 4 , wherein R4 and R5 taken together form the heterocyclic ring or the substituted heterocyclic ring structure.
8. The pharmaceutical agent of claim 7 , wherein R4 and R5 taken together form piperidine, piperazine, morpholine, or an alkyl or alkoxyl substituted piperidine, piperazine, or morpholine.
9. The pharmaceutical agent of claim 7 where Formula I is:
10. The pharmaceutical agent of claim 1 , wherein Formula I is the salt further comprising an anion and said anion is a halide, a polyatomic anion, or a basic active compound.
11. The pharmaceutical agent of claim 10 , wherein the anion is a chloride.
12. A method of imaging myelin basic protein in an open or minimally invasive surgical field by intravenous (IV) injection administration of a pharmaceutical agent comprising the steps of:
intravenously injecting a subject with the pharmaceutical agent, the pharmaceutical agent comprising a compound of Formula I or a salt thereof, wherein Formula I is:
wherein R1 is an alkyl group, R2 is an electron donating group and R3 is an electron withdrawing group; and
an aqueous pharmaceutical carrier, wherein the aqueous pharmaceutical carrier comprises, based on volume:
1-30% PEG-300, 1-20% propylene glycol and 1-10% polyvinylpyrrolidone;
detecting the pharmaceutical agent by applying a light source tuned to one or more spectral excitation characteristics of the agent; and
observing the subject through an optical filter tuned to the spectral emission characteristics of the agent.
13. The method of claim 12 , wherein the detecting is effected by fluorescence microscopy, laser-confocal microscopy, cross-polarization microscopy, autoradiography, or a combination thereof.
14. The method of claim 12 , wherein R1 is a lower alkyl group from 1 to 6 carbon atoms, R2 is a primary, secondary, or tertiary amine, or an alkoxy group.
15. The method of claim 12 , wherein Formula I is:
where R1 is the alkyl group, R2 is the electron donating group, and R4 and R5 are independently hydrogen, alkyl, substituted alkyl, amine, substituted amine, or taken together form a heterocyclic ring or a substituted heterocyclic ring structure.
16. The method of claim 15 , wherein the aqueous pharmaceutical carrier comprises 5-30 percent cyclodextrin based on volume.
17. The method of claim 16 , wherein the cyclodextrin comprises 2-hydroxypropyl-β-cyclodextrin.
18. The method of claim 15 , wherein R4 and R5 taken together form the heterocyclic ring or the substituted heterocyclic ring structure.
19. The method of claim 18 , wherein R4 and R5 taken together form piperidine, piperazine, morpholine, or an alkyl or alkoxyl substituted piperidine, piperazine, or morpholine.
20. The method of claim 19 , where Formula I is:
21. The method of claim 12 , wherein Formula I is a salt further comprising an anion and said anion is a halide, a polyatomic anion, or a basic active compound.
22. The method of claim 21 , wherein the anion is a chloride.
23. The method of claim 12 , further comprising determining the presence of myelin based on spectral excitation of the agent.
24. A kit for providing an intravenous (IV) injection administered pharmaceutical agent comprising:
a syringe;
a compound of Formula I or a salt thereof, wherein Formula I is:
wherein R1 is an alkyl group, R2 is an electron donating group and R3 is an electron withdrawing group; and
an aqueous pharmaceutical carrier, wherein the aqueous pharmaceutical carrier comprises, based on volume:
1-10% polyvinylpyrrolidone and at least one other solvent.
25. The kit of claim 24 , wherein the aqueous pharmaceutical carrier comprises one or more of a solubilizer, percutaneous enhancers, detergent, buffer solution, stabilizers, or preservatives.
26. The kit of claim 24 , wherein the aqueous pharmaceutical carrier comprises 5-30 percent based on volume of cyclodextrin.
27. The kit of claim 26 , wherein the cyclodextrin comprises 2-hydroxypropyl-β-cyclodextrin.
28. The kit of claim 24 , wherein the at least one other solvent comprises PEG-300 or propylene glycol.
29. The kit of claim 28 , wherein the PEG-300 is 1-30% based on volume.
30. The kit of claim 28 , wherein the propylene glycol is 1-20% based on volume.