EP2059187A2 - Utilisation de zéolites non-calciques avec sel de calcium ajouté dans des dispositifs hémostatiques, et produits - Google Patents

Utilisation de zéolites non-calciques avec sel de calcium ajouté dans des dispositifs hémostatiques, et produits

Info

Publication number
EP2059187A2
EP2059187A2 EP07841971A EP07841971A EP2059187A2 EP 2059187 A2 EP2059187 A2 EP 2059187A2 EP 07841971 A EP07841971 A EP 07841971A EP 07841971 A EP07841971 A EP 07841971A EP 2059187 A2 EP2059187 A2 EP 2059187A2
Authority
EP
European Patent Office
Prior art keywords
blood
zeolite
calcium
noncalcium
zeolites
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP07841971A
Other languages
German (de)
English (en)
Inventor
Robert L. Bedard
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Honeywell International Inc
Original Assignee
Honeywell International Inc
UOP LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Honeywell International Inc, UOP LLC filed Critical Honeywell International Inc
Publication of EP2059187A2 publication Critical patent/EP2059187A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/38—Silver; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Definitions

  • the present invention relates to blood clotting agents/medical devices and methods of controlling bleeding in animals and humans. More particularly, the present invention relates to the effectiveness of zeolites that have not been ion exchanged with calcium in promoting blood clotting provided that calcium ions are separately added along with the zeolites to the wound.
  • Blood is a liquid tissue that includes red cells, white cells, corpuscles, and platelets dispersed in a liquid phase.
  • the liquid phase is plasma, which includes acids, lipids, solubilized electrolytes, and proteins.
  • the proteins are suspended in the liquid phase and can be separated out of the liquid phase by any of a variety of methods such as filtration, centrifugation, electrophoresis, and immunochemical techniques.
  • One particular protein suspended in the liquid phase is fibrinogen. When bleeding occurs, the fibrinogen reacts with water and thrombin (an enzyme) to form fibrin, which is insoluble in blood and polymerizes to form clots.
  • thrombin an enzyme
  • compositions for promoting the formation of clots in blood have also been developed.
  • Such compositions generally comprise zeolites and binders.
  • the use of activated zeolites was disclosed by Hursey et al. in US 4,822,349. It was recognized that the use of these activated zeolites in the clotting of blood generated heat and Hursey et al. stated that the heat was important in achieving a cauterization effect as well as increasing coagulation of the blood.
  • US 2005/0074505 Al there is described the use of a zeolite that is exchanged with calcium ions to a very high level.
  • [T]he zeolite used for a blood clotting composition of the present invention includes an adjusted calcium content such that the calcium content is up to 83 wt-% calcium and preferably 75 wt-% to 83 wt-% calcium.”
  • An individual skilled in the art would interpret this patent to mean that the zeolites used were 75% and 83% exchanged with calcium (with reference to 100% of the cation exchange sites) rather than having the weight percentages of calcium indicated, since the bulk of the weight of the zeolites are silicon and aluminum by definition. It would be impossible for the weight percentage of the zeolite to be at the levels disclosed in the patent.
  • Calcium-exchanged zeolites do not function as hemostatic materials by release of Ca 2+ into the blood. They appear to function by surface activation of the intrinsic coagulation pathway.
  • the calcium form of a zeolite can be effective because it does not remove Ca 2+ by ion exchange from the blood during the activation process.
  • hemostatic products can be made from zeolites without a Ca + exchange step; provided that an effective amount of water soluble calcium salt is added to the zeolite as it is formulated into the hemostatic product. Much faster clotting has been found than is present with either the calcium salt or the noncalcium exchanged zeolite when used independently.
  • Noncalcium-exchanged zeolites have been found to accelerate blood clotting substantially as effectively as partially or fully dehydrated forms of calcium-exchanged zeolites when they are applied together with a calcium salt.
  • These noncalcium exchanged zeolites can include sodium zeolites, potassium zeolites, lithium zeolites, magnesium zeolites and combinations thereof.
  • the calcium salt is of low toxicity with noncoordinating anions and with solubility greater than 2 grams per 100 cc in 20 0 C water.
  • Useful calcium salts that can be used include calcium nitrate, calcium acetate, calcium bromide, calcium iodide, calcium nitrate and combinations thereof.
  • This apparatus measures the time until initial fibrin formation, the kinetics of the initial fibrin clot to reach maximum strength and the ultimate strength and stability of the fibrin clot and therefore its ability to do the work of hemostasis — to mechanically impede hemorrhage without permitting inappropriate thrombosis.
  • unactivated samples i. Pipet 360 uL from red topped tube into cup, start TEG test
  • activated samples i. First, obtain the zeolite or other powder sample to be tested from lab. They should be weighed, bottled, oven activated (if needed), and capped prior to the start of the experiment. Zeolite samples are bottled in twice the amount that need to be tested.
  • channel two is to test 5 mg of zeolite A and blood
  • the amount weighed out in the bottle for channel two will be 10 mg.
  • 10 mg samples 20 mg is weighed out, etc. See note below for reason.
  • ii. For one activated run, 3 zeolite samples were tested at a time. An unactivated blood sample with no additive is run in the first channel. Channels 2, 3 and 4 are blood samples contacted with zeolite.
  • iii. Once ready to test, set one pipet to 720 uL and other pipet to 360 uL. Prepare three red capped tubes (plain polypropylene-lined tubes without added chemicals) to draw blood and prepare three red additional capped tubes to pour zeolite sample into, iv.
  • the proportions are doubled for the initial mixing of blood and zeolite because some volume of blood is lost to the sides of the vials, and some samples absorb blood. Using double the volume ensures that there is at least 360 uL of blood to pipet into cup.
  • the proportion of zeolite to blood that we are looking at is usually 5mg/360uL, 10mg/360uL, and 30mg/360uL.
  • the R(min) reported in the Tables below is the time from the start of the experiment to the initial formation of the blood clot as reported by the TEG analyzer.
  • the TEG® analyzer has a sample cup that oscillates back and forth constantly at a set speed through an arc of 4°45'.
  • the resulting hemostasis profile is a measure of the time it takes for the first fibrin strand to be formed, the kinetics of clot formation, the strength of the clot (in shear elasticity units of dyn/cm ⁇ ) and dissolution of clot.
  • the tables below shows clotting data from unadulterated human blood as well as from the same blood with 5 and 10 ⁇ L of 0.2M CaCl 2 and in another experiment using a second unadulterated blood sample and with 20, 30, and 40 ⁇ L of 0.2M CaCl 2 added (each time the total volume was 360 ⁇ L). It is clear that the clotting time [R(min)] increases with increasing quantities of the Ca 2+ salt.
  • Zeolite powders that have not been ion exchanged with calcium have been found to be effective hemostats provided that a source of calcium is provided with the application of the zeolite.
  • the clotting times were slightly higher than with calcium exchanged zeolites, but still provided a significant acceleration in the clotting process.
  • these noncalcium exchanged zeolite promote blood clotting at a rate 2 to 12 times faster than in its absence.
  • These noncalcium exchanged zeolites promote blood clotting in less than 10 minutes and preferably these noncalcium exchanged zeolite promotes blood clotting in less than 5 minutes.
  • These zeolite powders may be combined with a binder such as clay, alumina or silica.
  • the zeolite powder that is functioning as a blood clot promoter may be contained within a porous carrier such as woven fibrous articles, non-woven fibrous articles, puffs, sponges and mixtures thereof.
  • Fibers used to make such woven or non-woven fibrous articles may include aramids, acrylics, cellulose, polyester, chemically modified cellulose fibers and mixtures thereof.
  • These zeolite powders can be used as free flowing powders or incorporated into a bandage, gauze or other formed product for treatment of wounds.
  • Various materials may be mixed with, associated with, or incorporated into the zeolites to maintain an antiseptic environment at the wound site or to provide functions that are supplemental to the clotting functions of the zeolites.
  • Exemplary materials that can be used include, but are not limited to, pharmaceutically-active compositions such as antibiotics, antifungal agents, antimicrobial agents, anti-inflammatory agents, analgesics (e.g., cimetidine, chloropheniramine maleate, diphenhydramine hydrochloride, and promethazine hydrochloride), bacteriostatics, compounds containing silver ions, and the like.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention concerne des zéolites à échange de calcium qui sont efficaces dans une hémostase. La raison pour laquelle des zéolites à échange de Ca sont nécessaires n'a pas été expliquée dans la technique antérieure, excepté que la présence d'ions Ca2+ est importante dans le mécanisme de coagulation. On sait maintenant que l'ajout d'ions Ca2+ ralentit réellement la coagulation du sang. L'utilisation de zéolites de Ca apparaît comme étant efficace dans une hémostase simplement du fait qu'elles ne suppriment pas le Ca2+ critique du sang par un échange d'ions. Une zéolite de NaA pourvue d'une quantité efficace de sel de Ca2+ ajouté est presque aussi active dans une coagulation que la forme à échange de Ca de zéolite de CaA.
EP07841971A 2006-09-08 2007-09-06 Utilisation de zéolites non-calciques avec sel de calcium ajouté dans des dispositifs hémostatiques, et produits Withdrawn EP2059187A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US53036906A 2006-09-08 2006-09-08
PCT/US2007/077763 WO2008030964A2 (fr) 2006-09-08 2007-09-06 Utilisation de zéolites non-calciques avec sel de calcium ajouté dans des dispositifs hémostatiques, et produits

Publications (1)

Publication Number Publication Date
EP2059187A2 true EP2059187A2 (fr) 2009-05-20

Family

ID=39158050

Family Applications (1)

Application Number Title Priority Date Filing Date
EP07841971A Withdrawn EP2059187A2 (fr) 2006-09-08 2007-09-06 Utilisation de zéolites non-calciques avec sel de calcium ajouté dans des dispositifs hémostatiques, et produits

Country Status (3)

Country Link
EP (1) EP2059187A2 (fr)
CN (1) CN101677848A (fr)
WO (1) WO2008030964A2 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2414225C1 (ru) * 2009-12-10 2011-03-20 Валерий Владимирович Бояринцев Местное гемостатическое средство

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5008202A (en) * 1988-11-29 1991-04-16 Sequoia Turner Corporation Blood diluent for red blood cell analysis
EP0906027A1 (fr) * 1996-04-25 1999-04-07 Unilever Plc Traitement du the a l'aide de zeolithes
US5861146A (en) * 1997-06-09 1999-01-19 The Procter & Gamble Company Method for reducing body odor
US6100414A (en) * 1998-04-02 2000-08-08 Eastman Chemical Company Cyclopentadienyl transition metal compounds useful as polymerization catalysts
US6521265B1 (en) * 2000-02-09 2003-02-18 Biolife, L.L.C. Method for applying a blood clotting agent
WO2002030479A1 (fr) * 2000-10-13 2002-04-18 On Site Gas Systems, Inc. Bandage utilisant des tamis moleculaires
US20040219208A1 (en) * 2001-08-03 2004-11-04 Ryu Kawamura Sustained-release medicines
US6989166B2 (en) * 2001-12-20 2006-01-24 N.V. Nutricia Soft drink replacer
WO2005027808A1 (fr) * 2003-09-12 2005-03-31 Z-Medica Corporation Agent hemostatique de zeolite de calcium
US20060178609A1 (en) * 2005-02-09 2006-08-10 Z-Medica, Llc Devices and methods for the delivery of molecular sieve materials for the formation of blood clots

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2008030964A3 *

Also Published As

Publication number Publication date
WO2008030964A2 (fr) 2008-03-13
CN101677848A (zh) 2010-03-24
WO2008030964A3 (fr) 2008-05-08

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