Bio-inorganic compound capable of stable, solid-state...

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

Reexamination Certificate

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C536S025400

Reexamination Certificate

active

06329515

ABSTRACT:

BACKGROUND OF THE INVENTION
The present invention relates to a bio-inorganic hybrid composite which is able to retain and carry bio-materials with stability and reversible dissociativity. Also, the present invention is concerned with a method for preparing such a bio-inorganic hybrid composite.
Generally, most inorganic compounds having lamellar structures, such as aluminosilicate, metal phosphate, etc, have a feature of being able to retain various materials in their interstices. In this regard, a variety of functional guest chemical species can be introduced into the interstices by subjecting the metal ions composing lattice layers to isomorphorous substitution to generate layer charges or modifying the lamellar in such a way that it is provided with physical and chemical absorptivity. Also, it is well known that the pore sizes of porous inorganic compounds, such as crosslink clay, MCM-41, etc, are controlled to physically adsorb selective sizes of molecules. Layered double hydroxides (hereinafter referred to as “LDH”), which are kinds of the inorganic compounds having lamellar structures, are called anionic clays, consisting of positively charged metal hydroxide layers between which anions counterbalancing the positive charges and water are intercalated.
As a rule, these composites are represented by the following chemical Formula:
[M
2+
1−x
N
3+
x
(OH)
2
][A
n−
]
x

.yH
2
O
wherein,
M is a bivalent metal cation, selected from alkaline earth metals or transition metals, such as Mg
2+
, Ni
2+
, Cu
2+
, Zn
2+
and the like,
N is a trivalent metal cation, selected from transition metals, such as Al
3+
, Cr
3+
, Fe
3+
, V
3+
, Ga
3+
and the like,
A is an anionic chemical species with n charges, such as NO
3

, CO
3
2−
, Cl

, SO
4
2−
, metalate, anions of organic acids, etc,
x is a rational number between 0 to 1; and
y is a positive number.
The layer charge densities of the composites can be controlled by changing the metal ratios according to x. Various anions, denoted by A in the LDH, can be easily introduced between the metal hydroxide layers through ion exchange reaction and coprecipitation.
LDH and their derivatives, which are of technical importance in catalytic reactions, are put into spotlight as lamellar nano-composites useful in various fields, including separation technology, optics, medical science, and engineering, and active research has been directed to the composites of interest. For example, hydrotalcite, a mineral name for the compounds based on magnesium and aluminum with similar structures to those of LDH, represented by [Mg
3
Al(OH)
8
]
+
[0.5CO
3
·mH
2
O]

, was investigated for the structure of intercalated carbonate anions and water by use of
1
H and
13
C-NMR [“Ordering of intercalated water and carbonate anions in hydrotalcite-An NMR study” Journal Physical Chemistry, 1994, 98, 4050-4054]. A synthesis method for crosslinking precursors of the Mg
3
Al LDH intercalated with hydroxides and adipate through ion exchange reaction with the aid of polyoxometalate (P
2
W
18
O
62
6−
or Co
4
(H
2
O)
2
(PW
9
O
34
)
2
10−
) and assay results for the structural and thermal properties of the resulting composites are reported in [“Layered double hydroxides intercalated by polyoxometalate anions with keggin (&agr;-H
2
W
12
O
40
6−
), dawson (&agr;-P
2
W
18
O
62
6−
), and finke (Co
4
(H
2
O)
2
(PW
9
O
34
)
2
10−
) structures”, Inorganic Chemistry, 1996, 35, 6853-6860]. Structural properties of some LDH are introduced, along with kinds and structures of possible metal cations and common intercalated anions in [“Crystal structures of some double hydroxide minerals”, Mineralogical Magazine, 1973, 39[304], 377-389]. A survey of LDH and their derivatives, including their historical backgrounds, possible-components (e.g., kinds of metal cations and intercalated anions), structural properties, and applicability is also found in [“Hydrotalcite-type anionic clays: Preparation, Properties and Applications”, catalysis Today, 1991, 11, 173-301].
Being useful as gene carriers, bacteria or cationic liposomes have a feasible possibility of causing side effects owing to their own toxicity and a problem of eliciting immune responses and showing poor expression rates.
Therefore, there remains a need for a structure for retaining and carrying bio materials.
SUMMARY OF THE INVENTION
Based on the fact that genetic materials have a structural property of being negatively charged owing to phosphoric ions, the present invention has an object of preparing a bio-inorganic hybrid composite by intercalating genetic materials in interstices of LDH through anion exchange. LDH is dissolved in acidic conditions, but remains stable in neutral and alkaline conditions. This attribute allows genes or bio materials to be put into or taken from LDH, freely, thereby making it possible for LDH to function as a preserver and carrier for genes or other bio materials. In addition, the bio-inorganic hybrid composite according to the present invention has significant advantages over conventional bio-material carriers, e.g., bacteria or cation liposomes, in that the bio-inorganic hybrid composite is composed of metal hydroxides harmless to the body and artificially controls the appropriate expression of the genetic materials retained therein.
The present invention has significance in that it is the first trial to make metal hydroxides used as a preserver and carrier for genes and bio-materials in the world.


REFERENCES:
patent: 5187260 (1993-02-01), Karali et al.
patent: 5389377 (1995-02-01), Chagnon et al.
patent: 5441746 (1995-08-01), Chagnon
patent: 5935866 (1999-08-01), Chagnon et al.
patent: 0987328 (2000-03-01), None
patent: 9218514 (1992-10-01), None
Romanowski et al., “Plasmid DNA in a Groundwater Aquifer Microcosm—Adsorption, DNAase Resistance and Natural Genetic Transformations of Bacillus Subtilis,”Molecular Ecology, 2(3), 171-181 (1993); see alsoChemical Abstracts, 120(11), p. 539, Abstract No. 129,352s (Mar. 14, 1994); Abstract supplied previously.*
Choy et al., “Intercalative Nanohybrids of Nucleoside Monophosphates and DNA in Layered Metal Hydroxide,”Journal of the American Chemical Society, 121(6), 1399-1400 (Feb. 17, 1999).*
Atkári et al., “Interactions of Aluminum(III) with Phosphates,”Inorganic Chemistry, 35(24), 7089-7094 (Nov. 20, 1996).*
Lovell et al., “Purification of DNA from Estuarine Sediments,”Journal of Microbiological Methods, 20(3), 161-174 (Sep., 1994).*
Chamier et al., “Natural transformation ofAcinetobacter calcoacetiusby Plasmid DNA Adsorbed on Sand and Grounwater Aquifer Material,”Applied and Environmental Microbiology, 59(5), 1662-1667 (May, 1993).*
Gold et al., “Adenosine Triphosphate-Derived Nucleotide Formation in the Presence of Ethanol,”Biochemical Pharmacology, 25, 1825-1830 (Aug. 15, 1976).*
Romanowski et al. (II), Adsorption of Plasmid DNA to Mineral Surfaces and Protection Aganist DNase I,Applied and Environmental Microbiology, 57(4), 1057-1061 (Apr., 1991).*
van der Pol, et al. (1994) Ordering of Intercalated Water and Carbonate Anions in Hydrotalcite. An NMR Study. Journal of Physical Chemistry vol. 98, p. 4050-4054.
Taylor, H.F.W. (1973) Crystal structures of some double hydroxide minerials. Mineralogical Magazine, vol. 39, No. 304; p. 377-389 (Dec., 1993).
Yun, S.K., et al. (1996) Layered Double Hydroxides Intercalated by Polyoxometalate Anions with Keggin (&agr;-H2W12O406-), Dawson (&agr;P2W18O626-), and Finke (Co4(H2O)2(PW9O34)210-) Structures. Inorg. Chem, 35, 6853-6860.

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