1. An immunogenic composition comprising at least 2 different N. meningitidis capsular saccharides, wherein one or more isare selected from a first group consisting of MenA, MenC, MenY and MenW which isare conjugated through a linker to a carrier protein(s), and one or more different saccharides isare selected from a second group consisting of MenA, MenC, MenY and MenW which isare directly conjugated to a carrier protein(s).
2. The immunogenic composition of claim 1 comprising at least 2 different N. meningitidis capsular saccharides, wherein one or more isare selected from a first group consisting of MenA and MenC which isare conjugated through a linker to a carrier protein(s), and one or more different saccharides isare selected from a second group consisting of MenC, MenY and MenW which isare directly conjugated to a carrier protein(s).
3. The immunogenic composition of claim 2 comprising MenA capsular saccharide conjugated through a linker to a carrier protein, and MenC capsular saccharide directly conjugated to a carrier protein.
4. The immunogenic composition of claim 2 comprising MenC capsular saccharide conjugated through a linker to a carrier protein, and MenY capsular saccharide directly conjugated to a carrier protein.
5. The immunogenic composition of claim 2 comprising MenA and MenC capsular saccharides conjugated through a linker to a carrier protein(s), and MenY and Men W capsular saccharides directly conjugated to a carrier protein(s).
6. The immunogenic composition of claim 2 comprising MenA capsular saccharide conjugated through a linker to a carrier protein, and MenC, MenY and Men W capsular saccharides directly conjugated to a carrier protein(s).
7. The immunogenic composition of any preceding claim wherein each N. meningitidis capsular saccharide is conjugated to a carrier protein independently selected from the group consisting of TT, DT, CRM197, fragment C of TT and protein D.
8. The immunogenic composition of any preceding claim wherein each N. meningitidis capsular saccharide is conjugated to the same carrier protein selected from the group consisting of TT, DT, CRM197, fragment C of TT and protein D.
9. The immunogenic composition of any preceding claim wherein each N. meningitidis capsular saccharide is conjugated to TT.
10. The immunogenic composition of any preceding claim wherein each N. meningitidis capsular saccharide is separately conjugated to a separate carrier protein.
11. The immunogenic composition of any preceding claim wherein each N. meningitidis capsular saccharide conjugate has a saccharide:carrier ratio of 1:5-5:1 or 1:1-1:4 (ww).
12. The immunogenic composition of any preceding claim wherein at least one, two or three N. meningitidis capsular saccharide conjugate(s) is directly conjugated to a carrier protein.
13. The immunogenic composition of claim 12 wherein Men W andor MenY, MenW andor MenC, MenY andor MenC, or MenW and MenC and MenY are directly conjugated to a carrier protein.
14. The immunogenic composition of claim 12 or 13 wherein at least one, two or three N. meningitidis saccharide conjugate(s) is directly conjugated by CDAP chemistry.
15. The immunogenic composition of any one of claims 12-14 wherein the ratio of Men W andor Y saccharide to carrier protein is between 1:0.5 and 1:2 (ww).
16. The immunogenic composition of any one of claims 12-15 wherein the ratio of MenC saccharide to carrier protein is between 1:0.5 and 1:2 (ww).
17. The immunogenic composition of any one of claims 1-16, wherein at least one, two or three N. meningitidis capsular saccharide(s) are conjugated to the carrier protein via a linker.
18. The immunogenic composition of claim 17 wherein the linker is bifunctional.
19. The immunogenic composition of claim 17 or 18 wherein the linker has two reactive amino groups.
20. The immunogenic composition of claim 17 or 18 wherein the linker has two reactive carboxylic acid groups.
21. The immunogenic composition of claim 17 or 18 wherein the linker has a reactive amino group at one end and a reactive carboxylic acid group at the other end.
22. The immunogenic composition of claim 17-21 wherein the linker has between 4 and 12 carbon atoms.
23. The immunogenic composition of claim 17 or 18 wherein the linker is ADH.
24. The immunogenic composition of any one of claims 17-23 wherein the or each N. meningitidis capsular saccharide(s) conjugated via a linker are conjugated to the linker with CDAP chemistry.
25. The immunogenic composition of claim 17-24 wherein the carrier protein is conjugated to the linker using carbodiimide chemistry, optionally using EDAC.
26. The immunogenic composition of any one of claims 17-25 wherein the or each N. meningitidis capsular saccharide is conjugated to the linker before the carrier protein is conjugated to the linker.
27. The immunogenic composition of any one of claims 17-26 wherein MenA is conjugated to a carrier protein via a linker.
28. The immunogenic composition of claim 27 wherein the ratio of MenA saccharide to carrier protein is between 1:2 and 1:5 (ww).
29. The immunogenic composition of any one of claims 17-28 wherein MenC is conjugated to a carrier protein via a linker.
30. The immunogenic composition of claim 34 wherein the ratio of MenC saccharide to carrier protein is between 1:2 and 1:5 (ww).
31. The immunogenic composition of any preceding claim comprising N. meningitidis capsular saccharides from at least two of serogroups A, C, W135 and Y conjugated to a carrier protein to produce a N. meningitidis capsular saccharide conjugate, wherein the average size of each N. meningitidis saccharide is above 50 kDa, 75 kDa, 100 kDa, 110 kDa, 120 kDa or 130 kDa.
32. The immunogenic composition of claim 31, wherein each N. meningitidis saccharide is either a native polysaccharide or is sized by a factor of no more than x10.
33. The immunogenic composition of claim 31 or 32 wherein each N. meningitidis capsular saccharide is a native polysaccharide.
34. The immunogenic composition of claim 31 or 32, wherein at least one, two, three or four N. meningitidis capsular saccharide(s) is sized by microfluidization.
35. The immunogenic composition of claim 31 or 32 wherein each N. meningitidis capsular saccharide is sized by a factor of no more than x10.
36. The immunogenic composition of claim 31 or 32 wherein the N. meningitidis conjugates are made from a mixture of native polysaccharides and saccharides that are sized by a factor of no more than x10.
37. The immunogenic composition of claim 36 wherein capsular saccharide from serogroup Y is sized by a factor of no more than x10.
38. The immunogenic composition of claim 36 or 37 wherein capsular saccharides from serogroups A and C are native polysaccharides and saccharides from serogroups W135 and Y are sized by a factor of no more than x10.
39. The immunogenic composition of claims 31-38 wherein the average size of each N. meningitidis capular saccharide is between 50 kDa and 300 KDa or 50 kDa and 200 kDa.
40. The immunogenic composition of claims 31-39 comprising a MenA capsular saccharide having an average size of above 50 kDa, 75 kDa, 100 kDa or an average size of between 50-100 kDa or 55-90 KDa or 60-80 kDa.
41. The immunogenic composition of claims 31-40 comprising a MenC capsular saccharide having an average size of above 50 kDa, 75 kDa, 100 kDa or between 100-200 kDa, 100-150 kDa, 80-120 kDa, 90-110 kDa, 150-200 kDa, 120-240 kDa, 140-220 kDa, 160-200 kDa or 190-200 kDa.
42. The immunogenic composition of claims 31-41 comprising a MenY capsular saccharide, having an average size of above 50 kDa, 75 kDa, 100 kDa or between 60-190 kDa or 70-180 kDa or 80-170 kDa or 90-160 kDa or 100-150 kDa, 110-145 kDa or 120-140 kDa.
43. The immunogenic composition of claims 31-42 comprising a MenW capsular saccharide having an average size of above 50 kDa, 75 kDa, 100 kDa or between 60-190 kDa or 70-180 kDa or 80-170 kDa or 90-160 kDa or 100-150 kDa, 140-180 kDa, 150-170 kDa or 110-140 kDa.
44. The immunogenic composition of any preceding claim wherein the dose of each saccharide conjugate is between 2 and 20 \u03bcg, 3 and 10 \u03bcg or 4 and 7 \u03bcg of saccharide.
45. The immunogenic composition of any preceding claim further comprising a H. influenzae b capsular saccharide (Hib) conjugated to a carrier protein.
46. The immunogenic composition of claim 45 wherein the H. influenzae b capsular saccharide is conjugated to a carrier protein selected from the group consisting of TT, DT, CRM197, fragment C of TT and protein D.
47. The immunogenic composition of claim 45 or 46, wherein the Hib saccharide is conjugated to the same carrier protein as for at least one, two, three or all of the N. meningitidis capsular saccharide conjugates.
48. The immunogenic composition of claims 45-47, wherein the Hib saccharide is conjugated to TT.
49. The immunogenic composition of claims 45-48 wherein the ratio of Hib to carrier protein in the Hib capsular saccharide conjugate is between 1:5 and 5:1 (ww).
50. The immunogenic composition of claim 49 wherein the ratio of Hib to carrier protein in the Hib capsular saccharide conjugate is between 1:1 and 1:4, 1:2 and 1:3.5 or around 1:3 (ww).
51. The immunogenic composition of claims 45-50 wherein the Hib capsular saccharide is conjugated to the carrier protein via a linker.
52. The immunogenic composition of claim 51 wherein the linker is bifunctional.
53. The immunogenic composition of claim 51 or 52 wherein the linker has two reactive amino groups.
54. The immunogenic composition of claim 51 or 52 wherein the linker has two reactive carboxylic acid groups.
55. The immunogenic composition of claim 51 or 52 wherein the linker has a reactive amino group at one end and a reactive carboxylic acid group at the other end.
56. The immunogenic composition of any one of claims 51-55 wherein the linker has between 4 and 12 carbon atoms.
57. The immunogenic composition of claim 51 or 52 wherein the linker is ADH.
58. The immunogenic composition of any one of claims 45-57 wherein the Hib saccharide is conjugated to the carrier protein or linker using CNBr or CDAP.
59. The immunogenic composition of claim 51-58 wherein the carrier protein is conjugated to the Hib saccharide via the linker using a method comprising carbodiimide chemistry, optionally EDAC chemistry.
60. The immunogenic composition of any one of claims 45-59 comprising a Hib saccharide conjugate and at least two further bacterial saccharide conjugates wherein the Hib conjugate is present in a lower dose than the mean dose of the at least two further bacterial saccharide conjugates.
61. The immunogenic composition of claim 60 wherein the Hib conjugate is present in a lower dose than the dose of each of the at least two further bacterial saccharide conjugates.
62. The immunogenic composition of claim 60 or 61 wherein the at least two further bacterial saccharide conjugates comprises N. meningitidis serogroup C capsular saccharide (MenC) conjugate.
63. The immunogenic composition of any one of claims 60-62 wherein the at least two further bacterial saccharide conjugates comprises N. meningitidis serogroup Y capsular saccharide (MenY) conjugate.
64. The immunogenic composition of any one of claims 60-63 wherein the at least two further bacterial saccharide conjugates comprises N. meningitidis serogroup A capsular saccharide (MenA) conjugate.
65. The immunogenic composition of any one of claims 60-64 wherein the at least two further bacterial saccharide conjugates comprises N. meningitidis serogroup W135 capsular saccharide (MenW) conjugate.
66. The immunogenic composition of any one of claims 60-65 wherein the at least two further bacterial saccharide conjugates comprise a S. pneumoniae capsular saccharide derived from a strain selected from the group consisting of serotypes 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 1A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and 33F.
67. The immunogenic composition of any one of claims 60-66 wherein the at least two further bacterial saccharide conjugates comprise a S. typhi Vi capsular saccharide.
68. The immunogenic composition of any one of claims 60-67 wherein the dose of the Hib saccharide conjugate is between 0.1 and 9 \u03bcg, 1 and 5 \u03bcg or 2 and 3 \u03bcg of saccharide.
69. The immunogenic composition of any one of claims 60-68 wherein the dose of each of the at least two further saccharide conjugates is between 2 and 20 \u03bcg, 3 and 10 \u03bcg or 4 and 7 \u03bcg of saccharide.
70. The immunogenic composition of any one of claims 60-69 wherein the saccharide dose of the Hib saccharide conjugate is less than 90%, 75% or 60%, between 20% and 60% or around 50% of the mean saccharide dose of the at least two further saccharide conjugates.
71. The immunogenic composition of any one of claims 60-70 wherein the saccharide dose of the Hib saccharide conjugate is less than 90%, 75% or 60% or is between 20-60% or is around 50% of the saccharide dose of each of the at least two further saccharide conjugates.
72. The immunogenic composition of any one of claims 60-71 wherein the same carrier protein is used in the Hib conjugate and two or more of the at least two further bacterial saccharide conjugates.
73. The immunogenic composition of any one of claims 1-72 comprising a N. meningitidis serogroup B outer membrane vesicle preparation or capsular saccharide.
74. A vaccine comprising the immunogenic composition of any one of claims 1-73 and a pharmaceutically acceptable excipient.
75. A vaccine kit for concomitant or sequential administration comprising two multi-valent immunogenic compositions for conferring protection in a host against disease caused by Bordetella pertussis, Clostridium tetani, Corynebacterium diphtheriae, Haemophilus influenzae and Neisseria meningitidis, said kit comprising a first container comprising
tetanus toxoid (TT),
diphtheria toxoid (DT), and
wholecell or acellular pertussis components
and a second container comprising:
the immunogenic composition of any one of claims 1-73.
76. A process for making the vaccine of claim 74 comprising the step of mixing the immunogenic composition of any one of claims 1-73 with a pharmaceutically acceptable exipient.
77. A method of immunising a human host against disease caused by Neisseria meningitidis infection comprising administering to the host an immunoprotective dose of the immunogenic composition or vaccine of claims 1-75.
78. The immunogenic composition of claims 1-73 for use in the treatment or prevention of disease caused by Neisseria meningitidis infection.
79. The use of the immunogenic composition of any one of claims 1-73 in the manufacture of a medicament for the treatment or prevention of diseases caused by Neisseria meningitidis infection.
80. An immunogenic composition comprising at least 2 different saccharides conjugated separately to the same type of carrier protein, wherein one or more saccharide(s) isare conjugated to the carrier protein via a first type of chemical group on the protein carrier, and one or more saccharide(s) isare conjugated to the carrier protein via a second type of chemical group on the protein carrier.
81. The immunogenic composition of claim 80, wherein the one or more saccharide(s) conjugated to the carrier protein via the first type of chemical group on the protein carrier, are different to the one or more saccharide(s) conjugated to the carrier protein via the second type of chemical group on the protein carrier.
82. An immunogenic composition of claim 80 or 81 comprising at least 2 different saccharides conjugated separately to the same carrier protein, wherein one or more saccharide(s) isare conjugated to the carrier protein via a carboxyl group on the protein carrier, and one or more saccharide(s) isare conjugated to the carrier protein via an amino group on the protein carrier.
83. An immunogenic composition of claims 80-82, wherein the first and second type of chemical group on the protein carrier are present on separate B- andor T-cell epitopes on the carrier protein.
84. An immunogenic composition of claims 80-83, wherein the saccharides are selected from a group consisting of: N. meningitidis serogroup A capsular saccharide (MenA), N. meningitidis serogroup C capsular saccharide (MenC), N. meningitidis serogroup Y capsular saccharide (MenY), N. meningitidis serogroup W capsular saccharide (MenW), Group B Streptococcus group I capsular saccharide, Group B Streptococcus group 11 capsular saccharide, Group B Streptococcus group III capsular saccharide, Group B Streptococcus group IV capsular saccharide, Group B Streptococcus group V capsular saccharide, Staphylococcus aureus type 5 capsular saccharide, Staphylococcus aureus type 8 capsular saccharide, Vi saccharide from Salmonella typhi, N. meningitidis LPS (such as L3 andor L2), M. catarrhalis LPS, H. influenzae LPS, and from any of the capsular pneumococcal saccharides such as from serotype: 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F or 33F.
85. The immunogenic composition of claims 80-84 wherein the carrier protein is selected from the group consisting of: TT, DT, CRM197, fragment C of TT and protein D.
86. The immunogenic composition of claims 80-84 wherein the carrier protein is TT.
87. An immunogenic composition of claims 80-86 comprising at least 2 different N. meningitidis capsular saccharides, wherein one or more isare selected from a first group consisting of MenA and MenC which isare conjugated to the carrier protein via the first type of chemical group on the protein carrier, and one or more different saccharides isare selected from a second group consisting of MenC, MenY and MenW which isare conjugated to the carrier protein via the second type of chemical group on the protein carrier.
88. An immunogenic composition of claim 87, wherein the first type of chemical group is a carboxyl group on the protein carrier, and the second type of chemical group is an amino group on the protein carrier.
89. The immunogenic composition of claims 87-88 comprising MenA conjugated via the first type of chemical group, and MenC conjugated via the second type of chemical group.
90. The immunogenic composition of claims 87-88 comprising MenC conjugated via the first type of chemical group, and MenY conjugated via the second type of chemical group.
91. The immunogenic composition of claims 87-88 comprising MenA conjugated via the first type of chemical group, and MenC, MenY and MenW conjugated via the second type of chemical group.
92. The immunogenic composition of claims 87-88 comprising MenA and MenC conjugated via the first type of chemical group, and MenY and MenW conjugated via the second type of chemical group.
93. The immunogenic composition of claims 87-92 further comprising a capsular saccharide from H. influenzae type b (Hib) conjugated to a carrier protein.
94. The immunogenic composition of claim 93, wherein Hib is conjugated to the same type of carrier protein as the N. meningitidis saccharides.
95. The immunogenic composition of claim 94, wherein Hib is conjugated to the carrier protein via either the first or second type of chemical group.
96. The immunogenic composition of claims 80-95, wherein the saccharides conjugated via the first type of chemical group do so through a linker, and the saccharides conjugated via the second type of chemical group do so directly, or wherein the saccharides conjugated via the second type of chemical group do so through a linker, and the saccharides conjugated via the first type of chemical group do so directly.
97. The immunogenic composition of claim 96 wherein the linker is bifunctional.
98. The immunogenic composition of claim 96 or 97, wherein the linker has between 4 and 12 carbon atoms.
99. The immunogenic composition of claims 96-98 wherein the linker has two reactive amino groups.
100. The immunogenic composition of claims 96-98 wherein the linker has two reactive carboxylic acid groups.
101. The immunogenic composition of claim claims 96-98 wherein the linker has a reactive amino group at one end and a reactive carboxylic acid group at the other end.
102. The immunogenic composition of claims 96-98 wherein the linker is ADH.
103. The immunogenic composition of claims 96-102, wherein the or each capsular saccharide(s) conjugated via a linker is conjugated to the linker with CDAP chemistry.
104. The immunogenic composition of claims 96-103, wherein the carrier protein is conjugated to the linker using carbodiimide chemistry, optionally using EDAC.
105. The immunogenic composition of claims 96-104, wherein the or each capsular saccharide is conjugated to the linker before the carrier protein is conjugated to the linker, or the linker is conjugated to the saccharide before it is conjugated to the carrier protein.
106. The immunogenic composition of claims 96-105, which is an immunogenic composition of claims 1-74.
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 composition, comprising: aspirin, magnesium, and nattokinase, and either niacin or nitroglycerine, said composition having a structural form that is suitable for being introduced into a body of a person.
2. The composition of claim 1, wherein the composition is adapted to be introduced into the body of the person for mitigating adverse effects of an imminent or actually-occurring pernicious thrombotic event in the person.
3. The composition of claim 2, wherein the pernicious thrombotic event in the person is a heart attack or stroke in the person.
4. The composition of claim 1, wherein the aspirin, magnesium, nattokinase, and niacin or nitroglycerine each have a therapeutically effective amount for mitigating adverse effects of an imminent or actually-occurring pernicious thrombotic event in the person.
5. The composition of claim 4, wherein the pernicious thrombotic event in the person is a heart attack or stroke in the person.
6. The composition of claim 1, wherein the structural form is a chewable form, and wherein the chewable form is adapted to being introduced into the mouth of the person.
7. The composition of claim 6, wherein the chewable form comprises a wafer or a chewable tablet.
8. The composition of claim 6, wherein the structural form is a dissolvable form, and wherein the dissolvable form is adapted to being introduced into the mouth of the person.
9. The composition of claim 1, wherein the structural form is a liquid form.
10. The composition of claim 1, wherein the structural form is a spray form, and wherein the spray form is adapted to being introduced into the nasal cavity of the person.
11. The composition of claim 1, wherein the structural form is a suppository form, and wherein the suppository form is adapted to being introduced into the anal cavity of the person.
12. The composition of claim 1, wherein the composition comprises niacin.
13. The composition of claim 12, wherein the aspirin has an amount in a range of 650 to 975 mg, wherein the magnesium has an amount in a range of 300 to 3000 mg, wherein the nattokinase has an amount in a range of 150 to 3000 mg, and wherein the niacin has an amount in a range of 500 to 3000 mg.
14. The composition of claim 12, further comprising L-carnitine.
15. The composition of claim 14, wherein the aspirin has an amount in a range of 650 to 975 mg, wherein the magnesium has an amount in a range of 300 to 3000 mg, wherein the nattokinase has an amount in a range of 150 to 3000 mg, wherein the niacin has an amount in a range of 500 to 3000 mg, and wherein the L-carnitine has an amount in a range of 2000 to 9000 mg.
16. The composition of claim 14, further comprising alpha lipoic acid.
17. The composition of claim 16, wherein the aspirin has an amount in a range of 650 to 975 mg, wherein the magnesium has an amount in a range of 300 to 3000 mg, wherein the nattokinase has an amount in a range of 150 to 3000 mg, wherein the niacin has an amount in a range of 500 to 3000 mg, wherein the L-carnitine has an amount in a range of 2000 to 9000 mg, and wherein the alpha lipoic acid has an amount in a range of 200 to 10000 mg.
18. The composition of claim 16, further comprising L-arginine.
19. The composition of claim 18, wherein the aspirin has an amount in a range of 650 to 975 mg, wherein the magnesium has an amount in a range of 300 to 3000 mg, wherein the nattokinase has an amount in a range of 150 to 3000 mg, wherein the niacin has an amount in a range of 500 to 3000 mg, wherein the L-carnitine has an amount in a range of 2000 to 9000 mg, wherein the alpha lipoic acid has an amount in a range of 200 to 10000 mg, and wherein the L-arginine has an amount in a range of 2000 to 12000 mg.
20. The composition of claim 18, further comprising coenzyme Q10.
21. The composition of claim 20, wherein the aspirin has an amount in a range of 650 to 975 mg, wherein the magnesium has an amount in a range of 300 to 3000 mg, wherein the nattokinase has an amount in a range of 150 to 3000 mg, wherein the niacin has an amount in a range or 500 to 3000 mg, wherein the L-carnitine has an amount in a range of 2000 to 9000 mg, wherein the alpha lipoic acid has an amount in a range of 200 to 10000 mg, wherein the L-arginine has an amount in a range of 2000 to 12000 mg, and wherein the coenzyme Q10 has an amount in a range of 300 to 6000 mg.
22. The composition of claim 1, wherein the composition comprises nitroglycerine.
23. The composition of claim 22, wherein the aspirin has an amount in a range of 650 to 975 mg, wherein the magnesium has an amount in a range of 300 to 3000 mg, wherein the nattokinase has an amount in a range of 150 to 3000 mg, and wherein the nitroglycerine has an amount in a range of 0.4 to 2.5 mg.
24. The composition of claim 22, further comprising L-carnitine.
25. The composition of claim 24, wherein the aspirin has an amount in a range of 650 to 975 mg, wherein the magnesium has an amount in a range of 300 to 3000 mg, wherein the nattokinase has an amount in a range of 150 to 3000 mg, wherein the nitroglycerine has an amount in a range of 0.4 to 2.5 mg, and wherein the L-carnitine has an amount in a range of 2000 to 9000 mg.
26. The composition of claim 24, further comprising alpha lipoic acid.
27. The composition of claim 26, wherein the aspirin has an amount in a range of 650 to 975 mg, wherein the magnesium has an amount in a range of 300 to 3000 mg, wherein the nattokinase has an amount in a range of 150 to 3000 mg, wherein the nitroglycerine has an amount in a range of 0.4 to 2.5 mg, wherein the L-carnitine has an amount in a range of 2000 to 9000 mg, and wherein the alpha lipoic acid has an amount in a range of 200 to 10000 mg.
28. The composition of claim 26, farther comprising L-arginine.
29. The composition of claim 28, wherein the aspirin has an amount in a range of 650 to 975 mg, wherein the magnesium has an amount in a range of 300 to 3000 mg, wherein the nattokinase has an amount in a range of 150 to 3000 mg, wherein the nitroglycerine has an amount in a range of 0.4 to 2.5 mg, wherein the L-carnitine has an amount in a range of 2000 to 9000 mg, wherein the alpha lipoic acid has an amount in a range of 200 to 10000 mg, and wherein the L-arginine has an amount in a range of 2000 to 12000 mg.
30. The composition of claim 28, further comprising coenzyme Q10.
31. The composition of claim 30, wherein the aspirin has an amount in a range of 650 to 975 mg, wherein the magnesium has an amount in a range of 300 to 3000 mg, wherein the nattokinase has an amount in a range of 150 to 3000 mg, wherein the nitroglycerine has an amount in a range of 0.4 to 2.5 mg, wherein the L-carnitine has an amount in a range of 2000 to 9000 mg, wherein the alpha lipoic acid has an amount in a range of 200 to 10000 mg, and wherein the L-arginine has an amount in a range of 2000 to 12000 mg, and wherein the coenzyme Q10 has an amount in a range of 300 to 6000 mg.