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EP-3758679-B1 - NITRIC OXIDE RELEASING SUPPOSITORIES AND METHODS OF USE THEREOF

EP3758679B1EP 3758679 B1EP3758679 B1EP 3758679B1EP-3758679-B1

Inventors

  • QHATTAL, Hussaini Syed Sha

Dates

Publication Date
20260506
Application Date
20190301

Claims (15)

  1. A vaginal suppository comprising: a nitric oxide-releasing active pharmaceutical ingredient, wherein the nitric oxide-releasing active pharmaceutical ingredient is a macromolecule that comprises a crosslinked or non-crosslinked polymer, dendrimer, metallic compound, organometallic compound, or inorganic-based compound, wherein the macromolecule has a molecular weight of 500 Daltons or greater, and wherein the nitric oxide-releasing active pharmaceutical ingredient comprises a diazeniumdiolate functional group as an NO donor; and a suppository base, wherein the nitric oxide-releasing active pharmaceutical ingredient is dispersed and/or dissolved within the suppository base, and wherein the vaginal suppository releases nitric oxide in an amount of 0.01% to 10% by weight of the vaginal suppository, as measured by real time in vitro release testing using a chemiluminescent nitric oxide analyzer.
  2. The vaginal suppository of claim 1, wherein the nitric oxide-releasing active pharmaceutical ingredient is present in an amount of 0.1% to 70% by weight of the vaginal suppository.
  3. The vaginal suppository of claim 1 or 2, wherein the suppository base is present in an amount of 0.01% to 99.91% by weight of the vaginal suppository, optionally wherein the suppository base is present in an amount of at least 70% by weight of the vaginal suppository.
  4. The vaginal suppository of any preceding claim, wherein the suppository base is hydrophobic or hydrophilic.
  5. The vaginal suppository of any preceding claim, wherein the vaginal suppository further comprises a buffering agent in an amount of 0.1% to 30% by weight of the vaginal suppository optionally wherein the vaginal suppository comprises at least two buffering agents, and wherein each of the at least two buffering agents is present in an amount of 0.1% to 30% by weight of the vaginal suppository.
  6. The vaginal suppository of any preceding claim, wherein the vaginal suppository further comprises a preservative in an amount of 0.1% to 2% by weight of the vaginal suppository.
  7. The vaginal suppository of any preceding claim, wherein the vaginal suppository further comprises a solvent in an amount of 0.1% to 99% by weight of the vaginal suppository, optionally wherein the solvent comprises acetone, methyl alcohol, ethanol, isopropanol, butyl alcohol, ethyl acetate, dimethyl isosorbide, propylene glycol, glycerin, ethylene glycol, polyethylene glycol, diethylene glycol monoethyl ether, water, and mixtures thereof.
  8. The vaginal suppository of any preceding claim, wherein the vaginal suppository further comprises a lubricant in an amount of 1% to 10% by weight of the vaginal suppository, optionally wherein the lubricant comprises magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene monostearate, talc, polyethyleneglycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, and mineral oil, or combinations thereof.
  9. The vaginal suppository of any preceding claim, wherein the vaginal suppository further comprises mineral oil in an amount of 1% to 20% by weight of the vaginal suppository.
  10. The vaginal suppository of any preceding claim, wherein the vaginal suppository further comprises one or more hard waxes in an amount of 1% to 20% by weight of the vaginal suppository.
  11. The vaginal suppository of any preceding claim, wherein the nitric oxide-releasing active pharmaceutical ingredient comprises a co-condensed silica network comprising diazeniumdiolated methylaminopropyl trimethoxysilane (MAP3) and tetraethyl orthosilicate (TEOS).
  12. The vaginal suppository of any preceding claim, wherein the vaginal suppository administers nitric oxide in an amount sufficient to induce apoptosis in virally infected cells.
  13. The vaginal suppository of any preceding claim, wherein the vaginal suppository administers nitric oxide in an amount sufficient to reduce or eliminate viral replication with less than 50% host cell cytotoxicity.
  14. The vaginal suppository of any preceding claim for use in treating and/or preventing an infection in a subject.
  15. The vaginal suppository of claims 1-13, or the vaginal suppository for use according to claim 14, wherein the vaginal suppository is a single phase system.

Description

Related Application Information This application claims the benefit of U.S. Provisional Patent Application Serial No. 62/637,120, filed March 1, 2018. Field The present invention relates generally to suppositories and such suppositories for use in methods of treating and/or preventing an infection (e.g., a viral infection). Summary It is noted that aspects described with respect to one embodiment may be incorporated in different embodiments although not specifically described relative thereto. NO-releasing suppositories (vaginal suppositories) are described herein. Some embodiments are directed to compositions, kits, and/or methods for treating and/or preventing an infection (e.g., a viral infection). In some embodiments, a method of treating and/or preventing a viral infection in a subject in need thereof is provided. Utoguchi et al. (Pharmaceutical Research, Vol. 15, No. 6, 1998) discloses suppositories comprising nitric oxide donors to enhance the rectal absorption of macromolecules. The foregoing and other aspects of the present invention will now be described in more detail with respect to other embodiments described herein. It should be appreciated that the invention can be embodied in different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Detailed Description The present invention will now be described more fully hereinafter. This invention may, however, be embodied in different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used in the description of the invention and the appended claims, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the present application and relevant art and should not be interpreted in an idealized or overly formal sense unless expressly so defined herein. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. In case of a conflict in terminology, the present specification is controlling. Also as used herein, "and/or" refers to and encompasses any and all possible combinations of one or more of the associated listed items, as well as the lack of combinations when interpreted in the alternative ("or"). As used herein, the transitional phrase "consisting essentially of" (and grammatical variants) is to be interpreted as encompassing the recited materials or steps "and those that do not materially affect the basic and novel characteristic(s)" of the claimed invention. See, In re Herz, 537 F.2d 549, 551-52, 190 U.S.P.Q. 461, 463 (CCPA 1976) (emphasis in the original); see also MPEP § 2111.03. Thus, the term "consisting essentially of" as used herein should not be interpreted as equivalent to "comprising." The term "about," as used herein when referring to a measurable value, such as an amount or concentration and the like, is meant to refer to variations of up to ± 20% of the specified value, such as, but not limited to, ± 10%, ± 5%, ± 1%, ± 0.5%, or even ± 0.1% of the specified value, as well as the specified value. For example, "about X" where X is the measurable value, is meant to include X as well as variations of ± 20%, ± 10%, ± 5%, ± 1%, ± 0.5%, or even ± 0.1% of X. A range provided herein for a measureable value may include any other range and/or individual value therein. As used herein, the terms "increase," "increases," "increased," "increasing," and similar terms indicate an elevation in the specified parameter of at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 150%, 200%, 300%, 400%, 500% or more. As used herein, the terms "reduce," "reduces," "reduced," "reduction," "inhibit," and similar terms refer to a decrease in the specified parameter of at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, or 100%. According to some embodiments of the present invention p