1. A composition comprising a crystalline form of L-ornithine phenyl acetate.
2. The composition of claim 1, wherein said crystalline form exhibits an X-ray powder diffraction pattern comprising at least one characteristic peak, wherein said characteristic peak is selected from the group consisting of approximately 6.0\xb0, 13.9\xb0, 14.8\xb0, 17.1\xb0, 17.8\xb0 and 24.1\xb0 2\u03b8.
3. The composition of claim 2, wherein said crystalline form exhibits an X-ray powder diffraction pattern comprising at least three characteristic peaks, wherein said characteristic peaks are selected from the group consisting of approximately 6.0\xb0, 13.9\xb0, 14.8\xb0, 17.1\xb0, 17.8\xb0 and 24.1\xb0 2\u03b8.
4. The composition of claim 2, wherein said crystalline form has a melting point of about 202\xb0 C.
5. The composition claim 1, wherein said crystalline form exhibits a single crystal X-ray crystallographic analysis with crystal parameters approximately equal to the following:
unit cell dimensions: a=6.594(2) \u212b, b=6.5448(18) \u212b, c=31.632(8) \u212b, \u03b1=90\xb0, \u03b2=91.12(3)\xb0, \u03b3=90\xb0;
Crystal System: Monoclinic; and
Space Group: P21.
6. The composition of claim 5, wherein the said crystalline form is represented by the formula C5H13N2O2C8H7O2.
7. The composition of claim 1, wherein said crystalline form exhibits an X-ray powder diffraction pattern comprising at least one characteristic peak, wherein said characteristic peak is selected from the group consisting of approximately 4.9\xb0, 13.2\xb0, 17.4\xb0, 20.8\xb0 and 24.4\xb0 2\u03b8.
8. The composition of claim 7, wherein said crystalline form exhibits an X-ray powder diffraction pattern comprising at least three characteristic peaks, wherein said characteristic peaks are selected from the group consisting of approximately 4.9\xb0, 13.2\xb0, 17.4\xb0, 20.8\xb0 and 24.4\xb0 2\u03b8.
9. The composition of claim 7, wherein said crystalline form comprises water andor ethanol molecules.
10. The composition of claim 9, wherein said crystalline form comprises about 11% by weight of said molecules as determined by thermogravimetric analysis.
11. The composition of claim 7, wherein said crystalline form is characterized by differential scanning calorimetry as comprising an endotherm at about 35\xb0 C.
12. The composition of claims 1, wherein said crystalline form exhibits a single crystal X-ray crystallographic analysis with crystal parameters approximately equal to the following:
unit cell dimensions: a=5.3652(4) \u212b, b=7.7136(6) \u212b, c=20.9602(18) \u212b, \u03b1=90\xb0, \u03b2=94.986(6)\xb0, \u03b3=90\xb0;
Crystal System: Monoclinic; and
Space Group: P21.
13. The composition of any one of claims 12, wherein the said crystalline form is represented by the formula C5H13N2O2C8H7O2EtOH.H2O.
14. The composition of claim 1, wherein said crystalline form exhibits an X-ray powder diffraction pattern comprising at least one characteristic peak, wherein said characteristic peak is selected from the group consisting of approximately 5.8\xb0, 14.1\xb0, 18.6\xb0, 19.4\xb0, 22.3\xb0 and 24.8\xb0 2\u03b8.
15. The composition of claim 14, wherein said crystalline form exhibits an X-ray powder diffraction pattern comprising at least three characteristic peaks, wherein said characteristic peaks are selected from the group consisting of approximately 5.8\xb0, 14.1\xb0, 18.6\xb0, 19.4\xb0, 22.3\xb0 and 24.8\xb0 2\u03b8.
16. The composition of claim 14, wherein said crystalline form is characterized by differential scanning calorimetry as comprising an endotherm at about 40\xb0 C.
17. The composition of claim 1, wherein said crystalline form exhibits an X-ray powder diffraction pattern comprising characteristic peaks at approximately 13.7\xb0, 17.4\xb0, 19.8\xb0, 20.6\xb0 and 23.7\xb0 2\u03b8.
18. The composition of claim 1, comprising:
at least about 50% by weight of said crystalline form of L-ornithine phenyl acetate salt; and
at least about 0.01% by weight benzoic acid or a salt thereof.
19. A process for making L-ornithine phenyl acetate salt comprising:
intermixing an L-ornithine salt, a benzoate salt and a solvent to form an intermediate solution;
intermixing phenyl acetate with said intermediate solution; and
isolating a composition comprising at least 70% crystalline L-ornithine phenyl acetate by weight.
20. The process of any one of claims 19, wherein the benzoate salt is silver benzoate.
21. A process for making L-ornithine phenyl acetate salt comprising:
increasing the pH value of a solution comprising an L-ornithine salt at least until an intermediate salt precipitates, wherein said intermediate salt is not an L-ornithine salt;
isolating the intermediate salt from said solution;
intermixing phenyl acetic acid with said solution; and
isolating L-ornithine phenyl acetate salt from said solution.
22. The process of claim 21, wherein increasing the pH value comprises adding a pH modifier selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium methoxide, potassium t-butoxide, sodium carbonate, calcium carbonate, dibutylamine, tryptamine, sodium hydride, calcium hydride, butyllithium, ethylmagnesium bromide or combinations thereof.
23. A process for making L-ornithine phenyl acetate salt comprising:
intermixing an L-ornithine salt, silver phenyl acetate and a solvent to form a solution, wherein the L-ornithine salt is in a halide salt; and
isolating L-ornithine phenyl acetate from said solution.
24. A method of treating or ameliorating hyperammonemia in a subject by administering a therapeutically effective amount of a crystalline form of L-ornithine phenyl acetate salt.
25. A method of treating or ameliorating hyperammonemia comprising intravenously administering a therapeutically effective amount of a solution comprising L-ornithine phenyl acetate, wherein said therapeutically effective amount comprises no more than 500 mL of said solution.
26. A method of compressing L-ornithine phenyl acetate, the method comprising applying pressure to a metastable form of L-ornithine phenyl acetate to induce a phase change.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A mirror reflective element assembly for an exterior rearview mirror assembly of a vehicle, said mirror reflective element assembly comprising:
a principal mirror element, said principal mirror element comprising a glass substrate and a first reflector coating disposed at a surface of said glass substrate to establish a principal reflector portion of said mirror reflective element assembly;
a wide angle mirror element, said wide angle mirror element comprising a glass element having a second reflector coating disposed at a surface of said glass element to establish an auxiliary reflector portion of said mirror reflective element assembly;
an illumination element comprising an illumination source, wherein said illumination element at least partially circumscribes said glass element of said wide angle mirror element;
wherein said illumination element, when said illumination source is activated, emits illumination at least partially around said glass element that is viewable by a person viewing an exterior rearview mirror assembly equipped with said mirror reflective element assembly when the equipped exterior rearview mirror assembly is disposed at a side of a vehicle equipped with the exterior rearview mirror assembly;
wherein said wide angle mirror element is disposed at an upper outboard portion of said mirror reflective element assembly when the equipped exterior rearview mirror assembly is disposed at the side of the equipped vehicle; and
wherein at least one of (i) said illumination element, responsive to determination that an ambient light level is below a threshold level, is operable to provide a light level that is less than about 100 candelas per square meter, and (ii) said illumination element, responsive to determination that an ambient light level is above a threshold level, is operable to provide a light level that is greater than about 200 candelas per square meter.
2. The mirror reflective element assembly of claim 1, comprising a back plate, wherein said principal mirror element is attached at said back plate.
3. The mirror reflective element assembly of claim 2, wherein said back plate comprises a receiving portion generally at said auxiliary reflector portion of said reflective element assembly, and wherein said receiving portion is configured to at least partially receive said wide angle mirror element.
4. The mirror reflective element assembly of claim 3, comprising a cover plate attached to said receiving portion, said cover plate substantially encasing said wide angle mirror element within said receiving portion.
5. The mirror reflective element assembly of claim 1, wherein said wide angle mirror element is disposed to the rear of a portion of said glass substrate of said principal mirror element, and wherein said illumination element is disposed to the rear of said glass substrate, and wherein, when said illumination source is activated, said illumination element emits illumination at least partially around said glass element that is viewable through said glass substrate by a person viewing the equipped exterior rearview mirror assembly when the equipped exterior rearview mirror assembly is disposed at the side of the equipped vehicle.
6. The mirror reflective element assembly of claim 5, wherein said first reflector coating is disposed at a front surface of said glass substrate and wherein a window is established at said first reflector coating, said window corresponding to a location of said wide angle mirror element and said illumination element.
7. The mirror reflective element assembly of claim 5, wherein said auxiliary reflector portion is devoid of said first reflector coating.
8. The mirror reflective element assembly of claim 5, wherein said glass element of said wide angle mirror element is adhered at a rear surface of said glass substrate via an optical adhesive, and wherein said optical adhesive has an index of refraction that is substantially similar to a refractive index of said glass substrate.
9. The mirror reflective element assembly of claim 1, wherein said first reflector coating comprises a different material than said second reflector coating.
10. The mirror reflective element assembly of claim 9, wherein said first reflector coating has a different tint than said second reflector coating.
11. The mirror reflective element assembly of claim 1, wherein, responsive to determination that an ambient light level is below a threshold level, said illumination element is operable to provide a light level that is less than about 100 candelas per square meter.
12. The mirror reflective element assembly of claim 1, wherein, responsive to determination that an ambient light level is above a threshold level, said illumination element is operable to provide a light level that is greater than about 200 candelas per square meter.
13. The mirror reflective element assembly of claim 1, wherein said illumination source of said illumination element is activated responsive to an object detection system of the equipped vehicle, and wherein said illumination element is activated responsive, at least in part, to said object detection system detecting an object present at or near the side of the equipped vehicle at which the equipped exterior rearview mirror assembly is mounted.
14. The mirror reflective element assembly of claim 1, wherein said illumination element is activated responsive to a turn signal indicator of the equipped vehicle, and wherein said illumination element is activated responsive, at least in part, to activation of a turn signal indicator at the side of the equipped vehicle at which the equipped exterior rearview mirror assembly is mounted.
15. A mirror reflective element assembly for an exterior rearview mirror assembly of a vehicle, said mirror reflective element assembly comprising:
a principal mirror element, said principal mirror element comprising a glass substrate and a first reflector coating disposed at a surface of said glass substrate to establish a principal reflector portion of said mirror reflective element assembly;
a wide angle mirror element, said wide angle mirror element comprising a glass element having a second reflector coating disposed at a surface of said glass element to establish an auxiliary reflector portion of said mirror reflective element assembly;
an illumination element comprising an illumination source, wherein said illumination element at least partially circumscribes said glass element of said wide angle mirror element;
wherein said illumination source comprises at least one light emitting diode;
wherein said illumination element, when said illumination source is activated, emits illumination at least partially around said glass element that is viewable by a person viewing an exterior rearview mirror assembly equipped with said mirror reflective element assembly when the equipped exterior rearview mirror assembly is disposed at a side of a vehicle equipped with the exterior rearview mirror assembly;
wherein said wide angle mirror element is disposed at an upper outboard portion of said mirror reflective element assembly when the equipped exterior rearview mirror assembly is disposed at the side of the equipped vehicle;
wherein at least one of (i) said illumination element, responsive to determination that an ambient light level is below a threshold level, is operable to provide a light level that is less than about 100 candelas per square meter, and (ii) said illumination element, responsive to determination that an ambient light level is above a threshold level, is operable to provide a light level that is greater than about 200 candelas per square meter; and
wherein at least one of (a) said illumination source of said illumination element is activated responsive to an object detection system of the equipped vehicle, and wherein said illumination element is activated responsive, at least in part, to said object detection system detecting an object present at or near the side of the equipped vehicle at which the equipped exterior rearview mirror assembly is mounted, and (b) said illumination element is activated responsive to a turn signal indicator of the equipped vehicle, and wherein said illumination element is activated responsive, at least in part, to activation of a turn signal indicator at the side of the equipped vehicle at which the equipped exterior rearview mirror assembly is mounted.
16. The mirror reflective element assembly of claim 15, comprising a back plate, wherein said principal mirror element is attached at said back plate, and wherein said back plate comprises a receiving portion generally at said auxiliary reflector portion of said reflective element assembly, and wherein said receiving portion is configured to at least partially receive said wide angle mirror element.
17. The mirror reflective element assembly of claim 15, wherein said first reflector coating comprises a different material than said second reflector coating.
18. A mirror reflective element assembly for an exterior rearview mirror assembly of a vehicle, said mirror reflective element assembly comprising:
a principal mirror element, said principal mirror element comprising a glass substrate and a first reflector coating disposed at a surface of said glass substrate to establish a principal reflector portion of said mirror reflective element assembly;
a wide angle mirror element, said wide angle mirror element comprising a glass element having a second reflector coating disposed at a surface of said glass element to establish an auxiliary reflector portion of said mirror reflective element assembly;
a back plate, wherein said principal mirror element and said wide angle mirror element are disposed at said back plate;
an illumination element comprising an illumination source, wherein said illumination element at least partially circumscribes said glass element of said wide angle mirror element;
wherein said illumination element, when said illumination source is activated, emits illumination at least partially around said glass element that is viewable by a person viewing an exterior rearview mirror assembly equipped with said mirror reflective element assembly when the equipped exterior rearview mirror assembly is disposed at a side of a vehicle equipped with the exterior rearview mirror assembly;
wherein said wide angle mirror element is disposed at an upper outboard portion of said mirror reflective element assembly when the equipped exterior rearview mirror assembly is disposed at the side of the equipped vehicle; and
wherein (i) said illumination element, responsive to determination that an ambient light level is below a threshold level, is operable to provide a light level that is less than about 100 candelas per square meter, and (ii) said illumination element, responsive to determination that an ambient light level is above a threshold level, is operable to provide a light level that is greater than about 200 candelas per square meter.
19. The mirror reflective element assembly of claim 18, wherein said principal mirror element is attached at said back plate, and wherein said back plate comprises a receiving portion generally at said auxiliary reflector portion of said reflective element assembly, and wherein said receiving portion is configured to at least partially receive said wide angle mirror element.
20. The mirror reflective element assembly of claim 18, wherein at least one of (a) said illumination source of said illumination element is activated responsive to an object detection system of the equipped vehicle, and wherein said illumination element is activated responsive, at least in part, to said object detection system detecting an object present at or near the side of the equipped vehicle at which the equipped exterior rearview mirror assembly is mounted, and (b) said illumination element is activated responsive to a turn signal indicator of the equipped vehicle, and wherein said illumination element is activated responsive, at least in part, to activation of a turn signal indicator at the side of the equipped vehicle at which the equipped exterior rearview mirror assembly is mounted.