1. A pharmaceutical combination useful for the treatment of viral infections comprising at least one of ()–D-2,6-diaminopurine-1,3- dioxolane(-D-DAPD) and ()–D-1,3-dioxolane guanine(-D-DXG) and at least one further therapeutic agent chosen from zidovudine, didanosine, zalcitabine, stavudine, lamivudine, nevirapine, delavirdine, efavirenz, indinavir, nelfinavir, saquinavir or ritonavir.
2. A pharmaceutical combination according to claim 1 wherein the -D-dioxolane is at least 97% free of the corresponding () enantiomer.
3. A pharmaceutical combination according to claim 1 wherein at least one further therapeutic agent is chosen from zidovudine, lamivudine, nevirapine and combinations thereof.
4. A pharmaceutical combination according to claim 2 wherein at least one further therapeutic agent is chosen from. zidovudine, lamivudine, nevirapine and combinations thereof.
5. A pharmaceutical combination according to claim 3 for use in medical therapy.
6. A pharmaceutical combination according to claim 4 for use in medical therapy
7. The pharmaceutical combination according to claim 3 for use in the treatment of HIV infection.
8. The pharmaceutical combination according to claim 4 for use in the treatment of HIV infection.
9. A pharmaceutical formulation comprising a pharmaceutical combination according to claim 1 with at least one pharmaceutically acceptable carrier or excipient.
10. A pharmaceutical formulation comprising a pharmaceutical combination according to claim 2 with at least one pharmaceutically acceptable carrier or excipient.
11. A pharmaceutical formulation comprising a pharmaceutical combination according to claim 3 with at least one pharmaceutically acceptable carrier or excipient.
12. A pharmaceutical formulation comprising a pharmaceutical combination according to claim 4 with at least one pharmaceutically acceptable carrier or excipient.
13. A pharmaceutical formulation comprising a pharmaceutical combination according to claim 7 with at least one pharmaceutically acceptable carrier or excipient.
14. A pharmaceutical formulation comprising a pharmaceutical combination according to claim 8 with at least one pharmaceutically acceptable carrier or excipient.
15. A pharmaceutical combination according to claim 1 wherein the anti-viral active compounds and the therapeutic agents are present in a synergistic ratio.
16. A pharmaceutical combination according to claim 2 wherein the antiviral active compounds and the therapeutic agents are present in a synergistic ratio.
17. A pharmaceutical combination according to claim 3 wherein the antiviral active compounds and the therapeutic agents are present in a synergistic ratio.
18. A pharmaceutical combination according to claim 4 wherein the antiviral active compounds and the therapeutic agents are present in a synergistic ratio.
19. A pharmaceutical combination according to claim 7 wherein the antiviral active compounds and the therapeutic agents are present in a synergistic ratio.
20. A pharmaceutical combination according to claim 8 wherein the antiviral active compounds and the therapeutic agents are present in a synergistic ratio.
21. A pharmaceutical combination according to claim 1 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:250 to about 250:1.
22. A pharmaceutical combination according to claim 1 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:50 to about 50:1.
23. A pharmaceutical combination according to claim 1 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:20 to about 20:1.
24. A pharmaceutical combination according to claim 2 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:250 to about 250:1.
25. A pharmaceutical combination according to claim 2 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:50 to about 50:1.
26. A pharmaceutical combination according to claim 2 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:20 to about 20:1.
27. A pharmaceutical combination according to claim 3 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:250 to about 250:1.
28. A pharmaceutical combination according to claim 3 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:50 to about 50:1.
29. A pharmaceutical combination according to claim 3 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:20 to about 20:1.
30. A pharmaceutical combination according to claim 4 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:250 to about 250:1.
31. A pharmaceutical combination according to claim 4 wherein the antiviral active compounds and the therapeutic. agents are present in a ratio between about 1:50 to about 50:1.
32. A pharmaceutical combination according to claim 4 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:20 to about 20:1.
33. A pharmaceutical combination according to claim 7 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:250 to about 250:1.
34. A pharmaceutical combination according to claim 7 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:50 to about 50:1.
35. A pharmaceutical combination according to claim 7 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:20 to about 20:1.
36. A pharmaceutical combination according to claim 8 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:250 to about 250:1.
37. A pharmaceutical combination according to claim 8 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:50 to about 50:1.
38. A pharmaceutical combination according to claim 8 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:20 to about 20:1.
39. A method for the treatment of viral infections comprising administering a therapeutically effective amount of at least. one of ()–D-2,6-diaminopurine-1,3- dioxolane(-D-DAPD) and ()–D -1,3-dioxolane guanine(-D-DXG) and at least one further therapeutic agent chosen from zidovudine, didanosine, zalcitabine, stavudine, lamivudine, nevirapine, delavirdine, efavirenz, indinavir, nelfinavir, saquinavir or ritonavir to a subject in need of such treatment.
40. The method of claim 39 wherein the -D-dioxclane is at least 97% free of the corresponding () enantiomer.
41. The method of claim 39 wherein at least one further therapeutic agent is chosen from zidovudine, lamivudine, nevirapine and combinations thereof.
42. The method of claim 40 wherein at least one further therapeutic agent is chosen from zidovudine, lamivudine, nevirapine and combinations thereof.
43. The method according to claim 41 wherein the viral infection is an HIV infection.
44. The method according to claim 42 wherein the viral infection is an HIV infection.
45. The method according to claim 39 wherein the compounds and the other therapeutic agents are administered sequentially.
46. The method according to claim 40 wherein the compounds and the other therapeutic agents are administered sequentially.
47. The method according to claim 43 wherein the compounds and the other therapeutic agents are administered sequentially.
48. The method, according to claim 44 wherein the compounds and the other therapeutic agents are administered sequentially.
49. The method according to claim 39 wherein the compounds and the other therapeutic agents are administered simultaneously.
50. The method according to claim 40 wherein the compounds and the other therapeutic agents are administered simultaneously.
51. The method according to claim 43 wherein the compounds and the other therapeutic agents are administered simultaneously.
52. The method according to claim 44 wherein the compounds and the other therapeutic agents are administered simultaneously.
53. The method of claim 39 wherein the antiviral active compounds and the therapeutic agents are present in a synergistic ratio.
54. The method of claim 40 wherein the antiviral active compounds and the therapeutic agents are present in a synergistic ratio.
55. The method of claim 43 wherein the antiviral active compounds and the therapeutic agents are present in a synergistic ratio.
56. The method of claim 44 wherein the antiviral active compounds and the therapeutic agents are present in a synergistic ratio.
57. The method of claim 39 wherein antiviral active compounds and the therapeutic agents are present in a ratio between about 1:250 to about 250:1.
58. The method of claim 39 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:50 to about 50:1.
59. The method of claim 39 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:20 to about 20:1.
60. The method of claim 40 wherein antiviral active compounds and the therapeutic agents are present in a ratio between about 1:250 to about 250:1.
61. The method of claim 40 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:50 to about 50:1.
62. The method of claim 40 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:20 to about 20:1.
63. The method of claim 43 wherein antiviral active compounds and the therapeutic agents are present in a ratio between about 1.250 to about 250:1.
64. The method of claim 43 wherein the antiviral active compounds and the therapeutic agents ate present in a ratio between about 1:50 to about 50:1.
65. The method of claim 43 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:20 to about 20:1.
66. The method of claim 44 wherein antiviral active compounds and the therapeutic agents are present in a ratio between about 1:250 to about 250:1.
67. The method of claim 44 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:50 to about 50:1.
68. The method of claim 44 wherein the antiviral active compounds and the therapeutic agents are present in a ratio between about 1:20 to about 20:1.
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 restraint for a vehicle having a wheel supportable by an elongate vehicle support, said restraint comprising:
(a) a winch shaft rotatably affixed to said vehicle support; and
(b) an elongate, flexible member having a first end portion restrainable to said winch shaft, a second end portion, and an intermediate portion between said first end and said second end portions, said second end portion and said intermediate portion respectively restrainable by said vehicle support, and a surface extending between said second end portion and said intermediate portion, said surface being capable of engaging and thereby restraining a circumferential surface of a wheel when said second end portion and said intermediate portion of said member are restrained by said vehicle support and tension is exerted in said member by winding said member on said winch shaft; said first end, said second end and said intermediate portions of said flexible member being respectively restrainable in alternative transverse positions with respect to said elongate vehicle support and winch shaft so as to align said flexible member laterally with said wheel.
2. The vehicle restraint of claim 1 wherein said second end portion and said intermediate portion of said flexible member are respectively restrainable by said vehicle support at alternative positions longitudinally of said elongate vehicle support.
3. The vehicle restraint of claim 1 wherein said flexible member is restrainable at said intermediate portion by an idler movably engageable with said flexible member and selectively engageable with said vehicle support.
4. The vehicle restraint of claim 1 wherein said flexible member is restrainable at said intermediate portion by movable engagement of said flexible member by said vehicle support.
5. The vehicle restraint of claim 1 wherein said alternative transverse positions are continuously adjustable with respect to a portion of said vehicle support so as to align said flexible member laterally with respect to said wheel despite small variations in lateral positioning of said wheel on said vehicle support.
6. The vehicle restraint of claim 1 further comprising a transducer capable of emitting at least one of an audible indication and a tactile indication of a magnitude of a tension force exerted in said flexible member.
7. The vehicle restraint of claim 6 wherein said transducer comprises:
(a) a bar having a thickness and a length extending between a first end arranged for selective engagement with said winch shaft and a second end;
(b) a tubular handle having an outer dimension, an inner dimension greater than said thickness of said bar, and arranged to encircle a portion of said length of said bar proximate said second end of said bar, said tubular handle being supported by said bar proximate a first end of said tubular handle and having a second end movable relative to said second end of said bar; and
(c) a detent arranged to support said second end of said bar within said inner dimension of said tubular handle and to release support of said bar when a force exerted by said handle on said bar exceeds a selected force, release of said support of said bar producing at least one of an audible indication and a tactile indication of tension in said flexible member.
8. The vehicle restraint of claim 1 wherein said winch shaft further comprises portions defining an axially elongate slot, said first end portion of said flexible member movable in said axially elongate slot to alternative positions transverse to said elongate vehicle support.
9. The vehicle restraint of claim 1 further comprising a winch drum axially movable with respect to said winch shaft but constrained to rotate with said winch shaft, said first end portion of said flexible member engageable with said winch drum.
10. A restraint for a vehicle having a wheel supportable by an elongate vehicle support, said restraint comprising:
(a) a winch including a winch shaft mounted for rotation but otherwise constrained relative to said vehicle support; and
(b) an elongate, flexible member having a first end portion restrainable to said winch, a second end portion, and an intermediate portion between said first end and said second end portions, said second end portion and said intermediate portion respectively restrainable by said vehicle support, and a surface extending between said second end portion and said intermediate portion, said surface being capable of engaging and thereby restraining a circumferential surface of a wheel when said second end portion and said intermediate portion of said member are restrained by said vehicle support and tension is exerted in said member by winding said member on said winch; said first end, said second end and said intermediate portions of said flexible member being respectively restrainable in continuously adjustable, alternative transverse positions with respect to said elongate vehicle support and said winch shaft so as to align said flexible member laterally with said wheel despite small variations in lateral positioning of said wheel on said vehicle support.
11. A restraint for a vehicle having a wheel supportable by an elongate vehicle support, said restraint comprising:
(a) a winch including a winch shaft mounted for rotation but otherwise constrained relative to said vehicle support;
(b) an elongate, flexible member having a first end portion restrainable to said winch, a second end portion, and an intermediate portion between said first end and said second end portions, said second end portion and said intermediate portion respectively restrainable by said vehicle support, and a surface extending between said second end portion and said intermediate portion, said surface being capable of engaging and thereby restraining a circumferential surface of a wheel when said second end portion and said intermediate portion of said member are restrained by said vehicle support and tension is exerted in said member by winding said member on said winch; said first end, said second end and said intermediate portions of said flexible member being respectively restrainable in alternative transverse positions with respect to said elongate vehicle support and said winch shaft so as to align said flexible member laterally with said wheel; and
(c) a transducer capable of emitting at least one of an audible indication and a tactile indication of a magnitude of a tension force exerted in said flexible member by said winch.
12. The vehicle restraint of claim 11 wherein said transducer comprises:
(a) a bar having a thickness and a length extending between a first end arranged for selective engagement with said winch shaft and a second end;
(b) a tubular handle having an outer dimension, an inner dimension greater than said thickness of said bar, and arranged to encircle a portion of said length of said bar proximate said second end of said bar, said tubular handle being supported by said bar proximate a first end of said tubular handle and having a second end movable relative to said second end of said bar; and
(c) a detent arranged to support said second end of said bar within said inner dimension of said tubular handle and to release support of said bar when a force exerted by said handle on said bar exceeds a selected force, release of said support of said bar producing at least one of an audible indication and a tactile indication of tension in said flexible member.
13. A restraint for a vehicle having a wheel supportable by an elongate vehicle support, said restraint comprising:
(a) a winch including a winch shaft mounted for rotation but otherwise constrained relative to said vehicle support, said winch shaft including portions defining an axially elongate slot; and
(b) an elongate, flexible member having a first end portion restrainable to said winch and movable in said axially elongate slot to alternative positions transverse to said elongate vehicle support, a second end portion, and an intermediate portion between said first end and said second end portions, said second end portion and said intermediate portion respectively restrainable by said vehicle support, and a surface extending between said second end portion and said intermediate portion, said surface being capable of engaging and thereby restraining a circumferential surface of a wheel when said second end portion and said intermediate portion of said member are restrained by said vehicle support and tension is exerted in said member by winding said member on said winch; said first end, said second end and said intermediate portions of said flexible member being respectively restrainable in alternative transverse positions with respect to said elongate vehicle support and said winch shaft so as to align said flexible member laterally with said wheel.
14. A restraint for a vehicle having a wheel supportable by an elongate vehicle support, said restraint comprising:
(a) a winch including a winch shaft mounted for rotation but otherwise constrained relative to said vehicle support and a winch drum axially movable with respect to said winch shaft but constrained to rotate with said winch shaft; and
(b) an elongate, flexible member having a first end portion engageable with said winch drum, a second end portion, and an intermediate portion between said first end and said second end portions, said second end portion and said intermediate portion respectively restrainable by said vehicle support, and a surface extending between said second end portion and said intermediate portion, said surface being capable of engaging and thereby restraining a circumferential surface of a wheel when said second end portion and said intermediate portion of said member are restrained by said vehicle support and tension is exerted in said member by winding said member on said winch; said first end, said second end and said intermediate portions of said flexible member being respectively restrainable in alternative transverse positions with respect to said elongate vehicle support and said winch shaft so as to align said flexible member laterally with said wheel.