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Oxides for Wound Healing and Body Repair

a wound healing and body technology, applied in the field of oxides for wound healing and body repair, can solve the problems of affecting the deposition rate of secondary bone and tissue growth, reducing the failure possibility of prostheses, and excessive heat generated locally at the injured si

Active Publication Date: 2010-08-19
RGT UNIV OF CALIFORNIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The invention provides a composition that can be used as a hemostatic, or blood clotting, agent. The composition is made up of a charged oxide, such as silicic acid or titanium dioxide, and a second oxide, such as calcium oxide or magnesium oxide. The charged oxide has an isoelectric point below 7.3 or above 7.4. The composition can be in the form of a sol-gel or a powder. It can also be prepared by co-assembling a bioactive glass sol with a structure-directing amount of a triblock copolymer. The composition can be used to decrease blood coagulation time or increase it, depending on the desired application. It can also be prepared by spraying droplets or passing a carrier gas through a solution. The invention also provides methods for preparing the hemostatic composition using different techniques.

Problems solved by technology

A major disadvantage to this product has been the excessive heat generated locally at the injured site as a consequence of the large enthalpy of hydration associated with the material currently marketed under the trade name, QuikClot™ and distributed by Z-medica corporation of Newington, Conn.
This has been shown to decreases the failure possibilities of prostheses and influence the deposition rate of secondary bone and tissue growth.

Method used

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  • Oxides for Wound Healing and Body Repair
  • Oxides for Wound Healing and Body Repair
  • Oxides for Wound Healing and Body Repair

Examples

Experimental program
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Effect test

example 1

Hemostatic Activity of Bioactive Glass

[0081] The time until clot detection, R, decreases for increasing Si:Ca ratios in BG (FIGS. 1, 2). R is reduced by a factor of 2 when the Si:Ca ratio is doubled over the range studied.

[0082] BG can perform the dual role of providing surface area for thrombosis and supplying Ca2+ ions; hence there will be an optimum ratio of SiO2 to Ca2+ ions, which are co-factors throughout the clotting cascade, for the fastest hemostatic response. The BG-induced coagulation rate, α, increases with increasing Si:Ca ratios and maximizes for the same Si:Ca ratio as for the minimum R time (Si:Ca(Rminαmax) ˜2.5). All blood clots induced by BGs resulted in stronger than natural clots (MABG≧62 and MANatural=58 dyn / cm2.

example 2

Formulation of Mesoporous Bioactive Glass

[0083] The unique formulation of high surface area mesoporous bioactive glass that we have prepared has the ability to rapidly induce a blood clot when exposed to blood. In fact, the formulation we have prepared has a faster clotting time and results in a stronger clot than QuikClot™, the leading inorganic hemostatic agent currently available (see FIG. 3). Both the porous and non-porous formulations of bioactive glass possess this ability to rapidly promote blood coagulation. Because the porous and non-porous formulations of bioactive glass can be hydrated to different degrees, and consequently will deliver different amounts of heat upon hydration during medical application to a wound site, we can further tailor the rate of blood coagulation. Combinations of porous and non-porous bioactive glass can be formulated to the desired specifications of hydration and delivery of heat (see FIG. 4).

example 3

Mesoporous Bioactive Glass with Varying Ratios of SiO2:CaO

[0084] This example shows that one make the bioactive glass with varying ratios of SiO2:CaO. At higher SiO2:CaO ratios (more silica), the material tends to clot blood faster. This is illustrated in both FIGS. 5 and 6. As the amount of SiO2 relative to the amount of CaO is reduced, the kinetics of clot formation are much slower. The difference in clotting kinetics between two bioactive glass samples with different SiO2:CaO is more pronounced with the non-porous samples. The mesoporous bioactive glass is a faster clotting agent than the non-porous samples, but the difference between samples is greater within the non-porous samples.

[0085] This example also shows that one can use combinations of porous and non-porous bioactive glass, as well as composites with multiple bioactive glasses of different SiO2:CaO ratios, to achieve any desired hydration capacity and heating response when in contact with blood (see FIGS. 7 and 8).

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Abstract

The invention provides a homogeneous composition comprising a hemostatically effective amount of a charged oxide, wherein the composition has an isoelectric point, as measured in calcium chloride, below 7.3 or above 7.4. Typically, the charged oxide is selected from the group consisting of silaceous oxides, titanium oxides, aluminum oxides, calcium oxides, zinc oxides, nickel oxides and iron oxides. In some embodiments, the composition further comprises a second oxide selected from the group consisting of calcium oxide, sodium oxide, magnesium oxide, zinc oxide, phosphorus oxide and alumina. In a typical embodiment of the invention, the charged oxide is silaceous oxide, the second oxide comprises calcium oxide and the ratio, by molar ratio, of silaceous oxide to calcium oxide is 0.25 to 15. Optionally, the composition further comprises phosphorous oxide. Also described are methods of making and using such compositions.

Description

[0001] This application is a continuation-in-part of U.S. patent application Ser. No. 11 / 398,161, filed Apr. 4, 2006, and claims the benefit of provisional patent application Nos. 60 / 708,206, filed Aug. 15, 2005, and 60 / 668,022, filed Apr. 4, 2005, the entire contents of each of which is incorporated herein by reference.GOVERNMENT RIGHTS [0002] This invention was made with Government support under Grant No. N00014-04-1-0654, awarded by the Office of Naval Research. The Government has certain rights in this invention.[0003] Throughout this application various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains. TECHNICAL FIELD OF THE INVENTION [0004] The invention disclosed herein relates to compositions and methods for modulating the blood coagulation cascade, accelerating bone generation, and assisting in...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K33/42A61K33/24
CPCA61K33/00A61K33/06A61K33/24A61K33/26A61L26/0004A61K33/42A61K45/06A61L24/02A61K33/30A61L2400/04
Inventor STUCKY, GALENOSTOMEL, TODDSHI, QIHUISAWVEL, APRILBAKER, SARAH
Owner RGT UNIV OF CALIFORNIA
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