Dietary calcium as a supplement to vitamin D compound...

Details Dietary calcium as a supplement to vitamin D compound... Dietary calcium as a supplement to vitamin D compound...

1999-07-08

2002-11-12

Criares, Theodore J. (Department: 1617)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

9,10-seco- cyclopentanohydrophenanthrene ring system doai

C424S687000

Reexamination Certificate

active

06479474

ABSTRACT:

CROSS-REFERENCE TO RELATED APPLICATION
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
BACKGROUND OF THE INVENTION
Vitamin D is a recent arrival in the roster of agents that are known to regulate the immune system. Vitamin D is converted in a two-step process to the hormone, 1,25-dihydroxycholecalciferol (1,25-(OH)
2
D
3
)
1
that is a key factor in regulating serum calcium, phosphorus and bone (DeLuca, 1997). This hormone acts in a steroid hormone-like mechanism through a nuclear receptor, the vitamin D receptor (VDR), which is a member of the steroid hormone receptor superfamily (Pike, 1991; Ross, et al., 1993). The discovery of VDR in peripheral blood lymphocytes (Bhalla, et al., 1983; Provvedini, et al., 1983) is a factor that led to the realization that 1,25-(OH)
2
D
3
is a significant regulator of the immune system. The most striking evidence of a role for 1,25-(OH)
2
D
3
as an immune system regulator comes from in vivo experiments. 1,25-(OH)
2
D
3
can prevent the development of EAE (Cantorna, et al., 1996 and U.S. Pat. No. 5,716,946; Lemire and Archer, 1991), experimental arthritis (Cantorna, et al., 1998a), and 1,25-(OH)
2
D
3
can markedly inhibit transplant rejection (Bouillon, et al., 1995; Hullett, et al., 1998).
1
Abbreviations: central nervous system, CNS; 1,25-dihydroxycholecalciferol, 1,25-(OH)
2
D
3
; experimental autoimmune encephalomyelitis, EAE; glyceraldehyde-3-phosphate dehydrogenase, lymph node, LN; multiple sclerosis, MS; interferon &ggr;, IFN-&ggr;; interleukin-4, IL-4; transforming growth factor &bgr;1, TGF-&bgr;1; tumor necrosis factor-&agr;, TNF-&agr;; type-1 helper, Th1; type-2 helper, Th2; vitamin D receptor, VDR.
EAE is mediated by CD4+ T cells, which mount an inappropriate immune-mediated attack on the central nervous system (CNS). Type-1 helper (Th1) cells specific for CNS antigens induce the disease and the Th1 cytokines interferon (IFN)-&ggr; and tumor necrosis factor (TNF)-&agr; are associated with EAE in mice (Holda and Swanborg, 1982; Powell, et al., 1990). Conversely, type-2 helper (Th2) cells and other cell types which produce interleukin (IL)-4 and transforming growth factor (TGF)-&bgr;1 in response to CNS antigens are known to ameliorate EAE. In vivo 1,25-(OH)
2
D
3
treatments result in a net loss in the total number of lymphocytes and a net increase in the expression of IL-4 and TGF-&bgr;1 (Cantorna, et al., 1998b). Conversely the in vivo 1,25-treatments had no effect on IFN-&ggr; or TNF-&agr; expression (Cantorna, et al., 1998b). The role, if any, for calcium in the regulation of the immune response remains unclear.
BRIEF SUMMARY OF THE INVENTION
The present invention is a method of more effectively treating multiple sclerosis patients. The method comprises the step of administration of an amount of calcium that renders a vitamin D compound effective in preventing or markedly reducing MS symptoms. Preferably, this amount of calcium is 0.5-2 g per patient per day. Most preferably, the amount is between 1 and 2 g of calcium as a salt with a variety of anions, e.g. CO
3
=
, PO
4
=
, Cl
2
−
acetate, gluconate, citrate, etc.
In one embodiment, the vitamin D compound is 1&agr;,25-dihydroxyvitamin D
3
(1,25-(OH)
2
D
3
), 19-nor-1,25-dihydroxyvitamin D
2
(19-nor-1,25-(OH)
2
D
3
), 24-homo-22-dehydro-22E-1&agr;,25-dihydroxyvitamin D
3
(24-homo-22-dehydro-22E-1,25-(OH)
2
D
3
), 1,25-dihydroxy-24(E)-dehydro-24-homo-vitamin D
3
(1,25-(OH)
2
-24-homo D
3
), or 19-nor-1,25-dihydroxy-21-epi-vitamin D
3
(19-nor-1,25-(OH)
2
-21-epi-D
3
). In a most preferred form of the invention, the compound used is 1,25(OH)
2
D
3
.
In another embodiment, the present invention is a pharmaceutical composition comprising an amount of vitamin D and an amount of calcium that renders the vitamin D compound more effective in reducing the multiple sclerosis symptoms.
It is an object of the present invention to more effectively diminish multiple sclerosis symptoms in a multiple sclerosis patient.
It is another object of the present invention to reduce the amount of vitamin D compound needed to alleviate MS symptoms.
Other features, advantages and objects of the present invention will become apparent to one of skill in the art after review of the specification, claims and drawings.


REFERENCES:
patent: 4279826 (1981-07-01), DeLuca et al.
patent: 4307025 (1981-12-01), DeLuca et al.
patent: 4448721 (1984-05-01), DeLuca et al.
patent: 4500460 (1985-02-01), DeLuca et al.
patent: 4502991 (1985-03-01), DeLuca et al.
patent: 4505906 (1985-03-01), DeLuca et al.
patent: 4552698 (1985-11-01), DeLuca et al.
patent: 4588528 (1986-05-01), DeLuca et al.
patent: 4594192 (1986-06-01), DeLuca et al.
patent: 4619920 (1986-10-01), DeLuca et al.
patent: 4698328 (1987-10-01), Neer et al.
patent: 4769181 (1988-09-01), DeLuca et al.
patent: 4973584 (1990-11-01), DeLuca et al.
patent: 5030772 (1991-07-01), DeLuca et al.
patent: 5036061 (1991-07-01), DeLuca et al.
patent: 5237110 (1993-08-01), DeLuca et al.
patent: 5260199 (1993-11-01), DeLuca et al.
patent: 5260290 (1993-11-01), DeLuca et al.
patent: 5328903 (1994-07-01), DeLuca et al.
patent: 5371249 (1994-12-01), DeLuca et al.
patent: 5373004 (1994-12-01), DeLuca et al.
patent: 5380720 (1995-01-01), DeLuca et al.
patent: 5395830 (1995-03-01), DeLuca et al.
patent: 5397775 (1995-03-01), DeLuca et al.
patent: 5414098 (1995-05-01), DeLuca et al.
patent: 5716946 (1998-02-01), DeLuca et al.
patent: 2096196 (1993-05-01), None
patent: 0 579 915 (1993-05-01), None
patent: 0 702 954 (1996-03-01), None
patent: 0 580 968 (1996-08-01), None
patent: 63104926 (1988-05-01), None
patent: WO 92/21355 (1992-12-01), None
patent: WO 95/01960 (1995-01-01), None
patent: WO 98/40085 (1998-09-01), None
patent: WO 93/51678 (1998-11-01), None
patent: WO 98/49138 (1998-11-01), None
patent: WO 00/66098 (2000-11-01), None
Goldberg, “Multiple sclerosis. Vitamin D and calcium as environmental determinants of prevalence. 2. Biochemical genetic factors” Int. J. Environ. Stud. (1974), 6(2-3), 121-9 Coden: IJEVAW. (1974).*
M.T. Cantorna, et al., “1,25-Dihydroxyvitamin D3Reversibly Blocks the Progression of Relapsing Encephalomyelitis, a Model of Multiple Sclerosis,”Proc. Natl. Acad. Sci. USA93: 7861-7864, 1996.
J.-F. Bach, “Immunosuppressive therapy of autoimmune diseases,”Immun. Today14 (6) :322-326, 1993.
Bhalla, Ashok K., et al., “1,25-Dihydroxyvitamin D3Inhibits Antigen-Induced T Cell Activation,”J. Immunol.,1984, 133:1748-54.
Branisteanu, D., et al., “Prevention of murine experimental allergic encephalomyelitis: cooperative effects of cyclosporine and 1&agr;25-(OH)2D3, ”J. Neuroimmun. 61(199):151-160, 1995.
S. Brocke, et al., “Infection and multiple sclerosis: a possible role for superantigens?”Trends in Microbiol.2(7) 250-254, 1994.
Cantorna, M., et al., “1,25-Dihydroxyvitamin D3reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis,”Proc. Natl. Acad. Sci. USA93:7861-7864, 1996.
Ebers, George C., et al., “A Population-Based Study of Multiple Sclerosis in Twins,”N. Engl. J. Med.,1986; 315:1638-42.
Ebers, George C., et al., “A full genome search in multiple sclerosis, ”Nature Genet.,1996, 13:472-76.
Haines, J.L., et al. (The Multiple Sclerosis Genetics Group), “A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex, ”Nature Genet.,1996, 13:469-71.
Lacey, David L., et al., “Vitamin D Affects Proliferation of a Murine T Helper Cell Clone,”J. Immunol., 1987, 138:1680-86.
Lemire, Jacques M., et al., “1&agr;, 25-Dihydroxyvitamin D3Supresses Proliferation and Immunoglobulin Production by Normal Human Peripheral Blood Mononuclear Cells, ”J. Clin. Invest., 1984, 74:657-61.
Lemire, J., et al., “1,25-Dihydroxyvitamin D3Prevents the In Vivo Induction of Murine Experimental Autoimmune Encephalomyelitis,”J. Clin. Invest.87:1103-1107, 1991.
Miller, S.D., and Karpus, W.J., “The immunopathogenesis and regulation of T-cell-mediated demyelinating diseases,”Immun. Today15(8) :356-361, 1994.
Müller, K., and Bendtzen, K., “Inhibition of Human T L

Affiliated with

Also associated with

Rating

Dietary calcium as a supplement to vitamin D compound... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Dietary calcium as a supplement to vitamin D compound..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Dietary calcium as a supplement to vitamin D compound... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2984880