JP-2025515314-A5 -

Dates

Publication Date

20260511

Application Date

20230425

Description

The compositions and methods of the attached claims are not limited to any specific compositions and methods described herein, but are intended as examples of some aspects of the claims, and any functionally equivalent compositions and methods are within the scope of this disclosure. In addition to those shown and described herein, various modifications of compositions and methods are intended to be included in the appended claims. Furthermore, while only certain representative compositions and aspects are specifically described, other compounds and methods are also intended to be included in the appended claims. Accordingly, in addition to the specific steps, elements, components, or combinations of elements explicitly mentioned herein, all other combinations of steps, elements, components, and elements not explicitly mentioned are also included in the scope. In certain embodiments, for example, the following are provided: (Item 1) Phosphate buffering agent, A composition comprising an aqueous carrier, A composition in which the pH of the composition is maintained in the range of 5.5 to 8.5, and the molar osmotic pressure concentration of the composition is 270 mOsm/kg to 1300 mOsm/kg. (Item 2) The phosphate buffer is the composition described in item 1, which contains potassium phosphate. (Item 3) The composition according to item 1 or 2, further comprising a pharmaceutical active ingredient. (Item 4) The composition described in item 3, wherein the aforementioned pharmaceutical active ingredient is a water-soluble pharmaceutical active ingredient. (Item 5) The composition according to item 3 or 4, wherein the active pharmaceutical ingredient comprises a mucolytic agent, an antibiotic, an antiviral agent, a corticosteroid, a monoclonal antibody (mAb), or an antifungal agent. (Item 6) The composition described in item 3 or 4 contains a nitric oxide (NO) releasing compound as the active pharmaceutical ingredient. (Item 7) The composition according to item 6, wherein the nitric oxide (NO)-releasing compound comprises at least two diazenium diolate groups present on one carbon atom, and each diazenium diolate group has a charge and each has a pharmaceutically acceptable cation to balance the charges on each diazenium diolate group, and the compound has a molecular weight of less than 500 g/mol, excluding the pharmaceutically acceptable cations. (Item 8) The aforementioned compound is a composition described in item 7 having the following structure: In the formula, R is hydrogen, deuterium, C1-12 alkyl , aryl, heteroaryl, alkylaryl, arylalkyl, or carbonyl, and is optionally substituted with one or more substituents, wherein the substituents are -OH, -NH2 , -OCH3 , -C(O)OH, -CH2OH , -CH2OCH3 , -CH2OCH2CH2OH , -OCH2C(O)OH, -CH2OCH2C(O)OH, -CH2C ( O)OH, -NHC ( O ) -CH3 , -C ( O)O ( ( CH2 ) aO)b-H, -C(O)O((CH2 ) aO ) b- ( CH2 ) cH , -C ( O ) O ( C1-5 alkyl ) , -C(O)-NH-((CH 2 ) d NH) e -H, -C(O)-NH-((CH2 ) d NH ) e -(CH2 ) f H , -O-((CH2 ) a O ) b -H, -O-((CH2 ) a O ) b -(CH2 ) c H , -O-( C1-5 alkyl), -NH-((CH2 ) d NH ) e -H, and -NH-((CH2 ) d NH ) e -(CH2 ) f H independently selected from the group consisting of, a, b, c, d, e, and f are each independently selected from the integers 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, and M + is a pharmaceutically acceptable cation, and the composition is such that the overall net charge of the compound becomes neutral depending on the ratio of the compound to the cation. (Item 9) The cation is selected from the group consisting of sodium, potassium, lithium, calcium, magnesium, ammonium, and substituted ammonium, as described in item 8. (Item 10) The aforementioned compound is a composition according to item 8 or 9 having the following structure: (Item 11) The aforementioned composition is a composition according to any one of items 8 to 10 having the following structure: (Item 12) The composition according to any one of items 8 to 11, wherein the molar equivalent concentration ratio of the phosphate buffer to the compound in the composition is at least 0.1:1. (Item 13) The phosphate buffer is the composition according to any one of items 1 to 12, which maintains the pH of the composition in the range of 5.5 to 8.0. (Item 14) The phosphate buffer is the composition according to any one of items 1 to 13, which maintains the pH of the composition in the range of 6.0 to 8.0. (Item 15) The phosphate buffer is the composition according to any one of items 1 to 14, which maintains the pH of the composition in the range of 6.7 to 7.5. (Item 16) The phosphate buffer is the composition according to any one of items 1 to 15, which maintains the pH of the composition in the range of 7.0 to 7.5. (Item 17) The composition is the composition according to any one of items 1 to 16, having a molar osmotic pressure concentration of 270 mOsm/kg to 1300 mOsm/kg. (Item 18) The composition according to item 17, wherein the molar osmotic pressure concentration is 270 mOsm/kg to 900 mOsm/kg. (Item