TREA

Drug delivery porphyrin compositions and methods

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Information

  • Patent Grant
  • 5284831
  • Patent Number
    5,284,831
  • Date Filed
    Thursday, April 16, 1992
    32 years ago
  • Date Issued
    Tuesday, February 8, 1994
    30 years ago
Information
Abstract
Description
Claims
  • 1. A composition, useful for delivery of boron atoms to cells, comprising:
  • a substantially non-toxic porphyrin compound having the structure ##STR14## where R.sup.3 is a closo-carborane and R.sup.2 is an alkyl or an aryl having 1 to about 7 carbon atoms; and
  • at least one lipoprotein with which the porphyrin compound is complexed.
  • 2. The composition as in claim 1 wherein R.sup.3 is a substituted or unsubstituted 1,2-icosahedral isomer or a 1,7-icosahedral isomer enriched in .sup.10 boron.
  • 3. The composition as in claim 1 wherein the porphyrin compound is substantially encapsulated by the at least one lipoprotein.
  • 4. The composition as in claim 3 wherein the at least one lipoprotein includes LDL.
  • 5. The composition as in claim 1 wherein R.sup.3 is a substituted or unsubstituted 1,2-icosahedral or 1,7-icosahedral isomer and R.sup.2 is methyl.
  • 6. A method of preparing a cellular drug delivery composition comprising:
  • providing a porphine precursor compound with substituents on at least two of the pyrrole rings thereof at pyrrole ring positions 2 and 4, the substituents including a glycol with two hydroxyl groups; and,
  • contacting the precursor compound with at least two equivalents of an acid chloride having the structure ##STR15## wherein R.sup.3 is a closo-carborane, the contacting conducted in the presence of a reaction rate enhancing amount of p-dimethylamino pyridine, to acylate at least one hydroxyl group of each bis-glycol sustituent and to form a porphine reaction product having at least one R.sup.3 group covalently bonded to each of the pyrrole rings at positions 2 and 4.
  • 7. The method as in claim 6 wherein the porphine precursor compound has substituents at pyrrole ring positions 6 and 7, the bis-glycol substituents being at pyrrole ring positions 2 and 4 and the substituents at positions 6 and 7 having the structure --C.sub.2 H.sub.4 --COOR.sup.2 and R.sup.2 is an alkyl or an aryl having 1 to about 7 carbon atoms.
  • 8. The method as in claim 7 where the rate enhancing amount of p-dimethylamino pyridine is less than about a 1:1 equivalent ratio of p-dimethylamino pyridine to the acid chloride.
  • 9. The method as in claim 8 wherein the p-dimethylamino pyridine is in an equivalent ratio with respect to the acid chloride of between about 0.5:1 to about 0.8:1.
  • 10. The method as in claim 6 wherein the precursor compound is contacted with at least about four equivalents of the acid chloride, and most of the porphine reaction product formed has the structure ##STR16## where R.sup.3 is a substituted or unsubstituted 1,2-icosahedral isomer, and R.sup.2 is an alkyl or aryl having 1 to about 7 carbon atoms.
  • 11. The method as in claim 10 wherein the acid chloride is in an amount of about 4.5 equivalents and the p-dimethylamino pyridine is in an amount of about 2 to about 4 equivalents.
  • 12. The method as in claim 6 wherein R.sup.3 is .sup.10 boron enriched.
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Divisions (1)
Number Date Country
Parent 616679 Nov 1990