EP0429645A1 - Ermässigung der verbreitung von infektionen während blutbehandlung mit geräten - Google Patents

Ermässigung der verbreitung von infektionen während blutbehandlung mit geräten

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Publication number
EP0429645A1
EP0429645A1 EP90917767A EP90917767A EP0429645A1 EP 0429645 A1 EP0429645 A1 EP 0429645A1 EP 90917767 A EP90917767 A EP 90917767A EP 90917767 A EP90917767 A EP 90917767A EP 0429645 A1 EP0429645 A1 EP 0429645A1
Authority
EP
European Patent Office
Prior art keywords
fatty acids
antiviral
monoglycerides
holding means
blood
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Withdrawn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
EP90917767A
Other languages
English (en)
French (fr)
Other versions
EP0429645A4 (en
Inventor
Charles E. Isaacs
Halldor Thormar
Kwang S. Kim
William C. Heird
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.)
Research Foundation for Mental Hygiene Inc
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Research Foundation for Mental Hygiene Inc
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Filing date
Publication date
Application filed by Research Foundation for Mental Hygiene Inc filed Critical Research Foundation for Mental Hygiene Inc
Publication of EP0429645A1 publication Critical patent/EP0429645A1/de
Publication of EP0429645A4 publication Critical patent/EP0429645A4/en
Withdrawn legal-status Critical Current

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/02Saturated carboxylic acids or thio analogues thereof; Derivatives thereof
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/06Unsaturated carboxylic acids or thio analogues thereof; Derivatives thereof
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/12Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group, wherein Cn means a carbon skeleton not containing a ring; Thio analogues thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/20Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/225Polycarboxylic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/22Lipids, fatty acids, e.g. prostaglandins, oils, fats, waxes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404Biocides, antimicrobial agents, antiseptic agents

Definitions

  • This application is directed to antiviral and antibacterial activity of fatty acids and
  • this application is directed to the inactivation of enveloped viruses and the killing of cells by fatty acids and
  • formulas do contain triglycerides which, following lipolysis in the stomach and intestine, produce free fatty acids and monoglycerides of which some have been shown to inactivate enveloped viruses and Giardia lamblia when present in human and bovine milk.
  • triglycerides which, following lipolysis in the stomach and intestine, produce free fatty acids and monoglycerides of which some have been shown to inactivate enveloped viruses and Giardia lamblia when present in human and bovine milk.
  • Figs. 1, 2, and 3 each represent a
  • Fig. 4 represents a cross-sectional view of a blood bag according to the invention.
  • Figs. 5a to 5c represent negative staining of VSV particles showing the effect of linoleic acid.
  • VSV was incubated at 37°C for 30 min. in (a) MM, (b) linoleic acid (0.5 mg/ml of MM), and (c) linoleic acid (1 mg/ml of MM) .
  • Fig. 5a normal intact particles covered with spikes;
  • Fig. 5b viral envelope no longer intact, allowing penetration of stain into most particles;
  • Figs. 6a to 6d represent scanning electron micrographs of all cultures showing the effect of human milk and linoleic acid. Vero cells were incubated at 37oC for 30 min in (a) human milk, (b) milk stored at 4°C for 4 days, (c) MM, or (d) linoleic acid (1 mg/ml of MM). Milk samples were diluted 1:5 in MM.
  • viruses that are virulent human pathogens have envelopes (pieces of membranes surrounding them). These include the AIDS virus (human
  • herpes viruses including herpes simplex virus (HSV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), Varicella/Zoster (VZ), Marek's disease virus, equine abortion virus, and pseudorabies virus.
  • HSV herpes simplex virus
  • EBV Epstein-Barr virus
  • CMV cytomegalovirus
  • VZ Varicella/Zoster
  • Marek's disease virus equine abortion virus
  • pseudorabies virus pseudorabies virus.
  • the viral envelope is essential for infectivity. While many compounds are able to destroy the envelope and inactivate the virus, a large number have toxic side effects in the body. Fatty acids and monoglycerides are normal metabolites in the body, notably formed during the breakdown of milk products. It has been found that fatty acids and/or monoglycerides may be
  • Lipids in fresh milk do not inactivate viruses but become antiviral after storage of the milk for a few days at 4° or 23oC.
  • the appearance of antiviral activity depends upon active milk lipases and correlates with the release of free fatty acids in the milk.
  • a number of fatty acids which are normal components of milk lipids were tested against enveloped viruses, i.e., vesicular stomatitis virus, herpes simplex virus, and visna virus, and against a nonenveloped virus, poliovirus.
  • Short-chain and long chain saturated fatty acids had no or a very small antiviral effect at the highest concentrations tested.
  • Medium-chain saturated and long-chain unsaturated fatty acids were all highly active against the enveloped viruses,
  • fatty acid concentration required for maximum viral inactivation varied by as much as 20-fold.
  • Monoglycerides of these fatty acids were also highly antiviral, in some instances at a concentration 10 times lower than that of the free fatty acids. None of the fatty acids inactivated poliovirus. Anti-viral fatty acids were found to affect the viral envelope, causing leakage and at higher concentrations, a complete disintegration of the envelope and the viral particles. They also caused disintegration of the plasma membranes of tissue culture cells resulting in cell lysis and death. The same phenomenon occurred in cell
  • Vero cells African green monkey kidney cell line; Flow Laboratories Inc., McLean, Va.
  • BME Eagle basal medium
  • fetal bovine serum inactivated fetal bovine serum (GIBCO). Sheep fibroblast cultures were obtained from the choroid plexus of a lamb brain and grown in 15% lamb serum (Colorado Serum Co.) in BME.
  • the maintenance medium (MM) for Vero cells was BME with 2% fetal bovine serum; for sheep cells, the MM was 2% lamb serum in BME. Gentamicin (0.1%) was added to all media.
  • VSV Vesicular Stomatitis Virus
  • HSV-1 Herpes Simplex Virus Type 1
  • Maclntyre obtained from the American Type Culture Collection, Rockville, Md., and grown in Vero cells.
  • Visna virus strain K796 was grown in sheep choroid plexus cells.
  • Poliovirus type 1 strain Chat was obtained from R.I. Carp (New York Institute of Basic Research) and grown in Vero cells.
  • Virus Titration Viruses were titrated by
  • Fatty acids and monoglycerides were purchased from Sigma Chemical Co., St. Louis, Mo. (purest grade). Monoglyceride ethers were custom synthesized by Peva Biotech, Inc., Paoli, Penna.
  • shortchain fatty acids were neutralized to pH 7 by addition of 1 M NaOH. Unsaturated fatty acids and monoglycerides were kept under nitrogen, and
  • Eserine sulfate (physostigmine; Sigma) and NaCl were dissolved in water and diluted in MM before use in experiments.
  • VSV was concentrated and partially purified by differential centrifugation in a Beckman L2-65B ultracentrifuge, and samples (10 TCID 50 /ml) were incubated at 37°C for 30 min. in MM with or without emulsified fatty acids.
  • the virus suspensions were applied to carbon-coated grids and negatively stained with 2% phosphotungstic acid, pH 7.0.
  • Specimens were examined by using a Hitachi HS 8-2 electron microscope at 50 kV.
  • Monolayer cultures of cells were incubated for 30 min. at 37°C either in MM alone or with milk or a fatty acid emulsion.
  • the cell layers were then carefully rinsed with Hanks balanced salt solution and fixed with 2% glutaraldehyde in 0.1 M cacodylate buffer. After rinsing in buffer and postfixation with 2% osmium tetroxide, the cells were dehydrated through gradings of ethanol, critical-point dried, and sputter coated with 10.5 nm of gold. They were examined in an ISI-ISS40 scanning electron
  • Electron micrographs with negative staining of VSV incubated with linoleic acid showed that at 0.5 mg per ml leakage of viral envelopes was produced allowing the stain to enter many particles. The effect was far more pronounced with 1 mg of linoleic acid per ml, causing particle disintegration.
  • VSV was concentrated, partly purified, and then
  • microscopy showed a 10-fold reduction in virus titer with 0.5 mg of linoleic acid per ml, whereas 1 mg/ml caused a ⁇ 1, 000-fold reduction. Similar results were obtained by negative staining of VSV incubated with low concentrations of arachidonic acid.
  • Negative staining of VSV treated with fatty acids suggested that virus inactivation results from disruption of the viral envelope, which is derived from the host cell plasma membrane.
  • monolayers of Vero cells or sheep fibroblasts were incubated at 37°C for 30 min. in MM with or without 1 mg of linoleic acid per ml and examined by scanning electron microscopy.
  • Figs. 5a to 5c reflect negative staining of VSV particles showing the effect of linoleic acid treatment. Titration of the samples used for electron microscopy showed a
  • the ability to make antiviral mixtures of medium and long-chain fatty acids indicates that a balance can be made between the potentially toxic effects of high concentrations of medium chain fatty acids in vivo and the loss of antiviral long-chain fatty acids by binding to serum albumin and other blood proteins.
  • HIV was diluted five-fold with sIgA depleted milk or stomach contents. Therefore, anti-HIV activity in the undiluted sample is greater than the 1,000 to 100,000-fold reduction in titer in the assay mix.
  • HIV is as sensitive to inactivation by milk lipids as the other enveloped viruses that were tested. It should, therefore, be possible to screen large numbers of lipid mixtures against HSV-1, for example, which is much less expensive to assay than HIV and then test only the promising mixtures against HIV.
  • the incubation mixture contained human serum, HSV-1 (titer 5.5), and the indicated monoglyceride.
  • the incubation mixture contained formula, HSV-1, (titer 5.5), and the indicated monoglyceride.
  • monolinolein produced the same reduction in viral titer as monocaprin but at one-third the concentration (millimolar).
  • Each MG was used at 2 mg/ml.
  • epidermidis treated with monolaurin showed that the bacteria were completely disintegrated. It is therefore possible to manipulate MGs and their concentrations to lyse some membranes and leave others intact.
  • the appearance of antiviral activity in stored milk is related to the level of lipoprotein lipase in the milk, indicating that it is caused by the release of fatty acids or other products of lipid hydrolysis. Similar results were previously reported by Welsh et al. (I, II). Data herein indicate that the antiviral effect of stored human milk is caused by lipolysis, and of the nine fatty acids most commonly found in human milk, seven are highly active in killing enveloped viruses.
  • the polyunsaturated long-chain fatty acids were the most active, but medium-chain saturated fatty acids, particularly lauric and myristic acids, also showed activity.
  • Monocaprin and monolaurin were active in concentrations ten times lower than those of the corresponding free acids, but monomyristin was consistently less active.
  • Long-chain saturated fatty acids which make up about 30% of the fatty acids in human milk, and short-chain fatty acids, which are more common in cow milk, were not, or were very slightly, antiviral. The concentrations of fatty acids found to reduce viral titers by
  • intestinal pathogens This may also be true for the members of each lipid class.
  • necrotizing enterocolitis in infants is caused by an enveloped virus, i.e., a human enteric coronavirus.
  • Giardia lamblia an intestinal protozoan parasite infecting children, is killed by milk fatty acids in vitro, suggesting the possibility of a giardiacidal effect of fatty acids in the intestines. Since fatty acids lyse cells by disrupting their plasma membranes, it is likely that they kill not only giardia but also other parasitic protozoa.
  • fatty acids and/or monoglycerides thereof are used for antiviral and/or antibacterial activity.
  • the compounds used can be selected from the group consisting of saturated or unsaturated fatty acids having from 4 to 22 carbon atoms and esters of glycerol with said acids.
  • Preferred compounds comprise saturated fatty acids having from 4 to 14 carbon atoms, particularly from 6 to 14 carbon atoms, and monoglycerides thereof.
  • C 7 - C 12 fatty acid monoglycerides either singly or in mixtures thereof.
  • Also useful according to the invention are mono- or
  • polyunsaturated fatty acids having from 14 or 16 to 22 carbon atoms, especially from 14 to 18, 16 to 18 or 16 to 20 carbon atoms, and the monoglycerides thereof.
  • the above-mentioned ranges of carbon atoms are inclusive of fatty acids having odd numbered carbon atoms.
  • fatty acids having antiviral and/or antibacterial activity useful fatty acid derivatives would have an ether bond between a fatty acid and glycerol.
  • useful fatty acid derivatives would have an ether bond between a fatty acid and glycerol.
  • examples of such compounds include 1-O-decyl-SN-glycerol,
  • lysophosphatidylcholine derivatives include, for example, L- ⁇ -lysophosphatidylcholine caproyl,
  • the fatty acids useful according to the invention can be used in the form of their pharmacologically acceptable salts, such as alkali metal salts.
  • pharmacologically acceptable salts such as alkali metal salts.
  • Useful examples of such salts include the sodium and lithium salts.
  • the compounds according to the invention can be used singly or in mixtures. For example, it is preferred that from 1 to 6 compounds, especially from 1 to 4 compounds, be administered at one time.
  • the 8 carbon and 10 carbon MG ethers are just as effective as the naturally occurring esters, and, in fact, the 8 carbon derivative appears to be somewhat more antiviral than the 8 carbon ester.
  • the 18 carbon ether (Table 12) showed the same lack of antiviral activity as the ester in human plasma.
  • LPL blood enzyme lipase
  • LPL inhibitors reduce or deter such breakdown.
  • Useful LPL inhibitors include, for example, the following:
  • Bile salts or acids and conjugated bile salts or acids at concentrations of from about 1 nanomolar to 1 molar.
  • An example of a conjugated bile acid is taurocholic acid, the sodium and lithium salts of which are readily available. Bile salts are also detergents, and therefore they provide additional antiviral activity;
  • concentrations of from about 1 nanomolar to 1 molar.
  • LPL inhibitors when used with, for example, monoglycerides according to the invention, they can be used in an MM:MM ratio of from about 1:1 to 1:6, based upon the monoglyceride or monoglycerides used. Preferably this ratio is from about 1:1.5 to 1:4.
  • the conjugated bile acid taurochloric acid sodium salt
  • an incubation mixture containing herpes antibody negative human serum, herpes simplex virus-1 (titer) 5.5, and a monoglyceride
  • a quantity of 12 MM (final concentration) sodium taurochlorate was added to some of the samples. The results were as follows:
  • 1-Monodecanoyl-rac-glycerol monoglycerides are used with varying concentrations of sodium taurocholate, the 1-Monodecanoyl-rac-glycerol is effective when used with concentrations as low as 2 MM sodium taurocholate whereas the
  • VSV titer (log 10 )
  • antiviral activity of monoglycerides depends upon the endogenous LPL activity in each blood sample. Since LPL activity is variable and each blood sample will not be tested for LPL activity, it would be preferred to add LPL inhibitors and monoglycerides to each clinical blood sample to ensure maximum antiviral activity. Also, since. the addition of. lithium taurocholate does not interfere with any clinical assays tested, it provides added antiviral activity with no drawbacks.
  • virus or bacteria-containing media such as blood
  • virus or bacteria-containing media such as blood
  • a human or warm-blooded animal having a viral or bacterial condition may be treated for said condition by administration of a composition according to the invention.
  • compositions consisting essentially of an inert pharmaceutical carrier and an effective amount of active
  • ester derivatives are antiviral and do not interfere with the clinical assays examined with the exception of triglyceride measurements. Since triglyceride concentration is determined by the enzymatic release of fatty acids from the glycerol backbone, monoglycerides push these measurements off scale on the high side. By using ether linkages rather than ester linkages, the fatty acid remains attached to the glycerol backbone because lipases do not work on ether linkages and the triglyceride measurements are unaffected.
  • sodium taurocholate is effective as an LPL inhibitor and has antiviral activity
  • other physiologically acceptable salts such as lithium salts
  • lithium taurocholate instead of the sodium salt, any interference with blood sodium measurements has been eliminated.
  • monoglyceride ether and lithium taurocholate was in excess of what is needed to inactivate ⁇ 4 log 10 of any enveloped virus in all of the blood and blood products examined. Further testing has shown the effect of monoglyceride esters and ether on the total white blood cell concentration in whole human blood. The results of said testing are as follows:
  • the Abott's kits tested were: HBsAg (hepatitis B surface antigen); Anti-HBc (anti-hepatitis B core antigen); Anti-HBs (anti-hepatitis B surface antigen); Anti-HBcIgM (anti-hepatitis B core IgM); Anti-HAVIgM (hepatitis Be antigen); Anti-HBe (anti-hepatitis Be antigen); Anti-delta hepatitis.
  • the MA Bioproduct ELISA kits tested were: mumps antibody; Herpes simplex type I antibody; Herpes Simplex type II antibody;
  • Toxoplasmosis antibody CMV antibody
  • Rubella antibody Measles antibody
  • Chlamydia antibody Positive and negative test results remained
  • ETOH add 1 ⁇ l of ETOH to 100 ⁇ l of serum and th mixture before running the test.
  • Anti-HBcIgM Anti-hepatitis B core IgM
  • Anti-HAV IgM Anti-hepatitis A IgM
  • HBeAg Hepatitis Be Antigen
  • a test tube 1 a representative example of blood handling equipment, may comprise at its closed end 2 an effective amount of liquid or powder active ingredient 3.
  • a blood product such as blood serum (not shown)
  • the open end 4 is closed with a stopper 5.
  • the test tube and stopper are then shaken for a sufficient amount of time to cause active ingredient 3 to dissolve in the blood serum.
  • the blood serum could be stirred or agitated with an
  • the liquid or powder 3 may comprise active ingredient alone or active ingredient in combination with suitable physiologically or pharmacologically acceptable carrier or diluent. It is within the scope of the invention that the liquid or powder 3 could be, with or without carrier or diluent, in the form of a capsule or pill (not shown) formed from conventional ingredients.
  • the pill could be coated or uncoated; however, if the pill has a coating, the coating would preferably be a readily soluble or dissolvable coating, in the same manner that the exterior capsule material would necessarily be readily soluble or dissolvable.
  • the liquid or powder 3, whether in pill or capsule form or not, can be added either prior to or after introduction of a blood product.
  • a premeasured quantity of powder or a pill could be added to a test tube containing a blood product.
  • Fig. 2 the interior surface 10 of the test tube 1 is coated with a coating 11 comprising an effective amount of active ingredient and suitable carrier.
  • the interior surface 10 can be either partly or wholly coated, depending upon the
  • a partial coating 11 could be continuous or
  • the closed end 2 is coated since this surface is most likely to be in contact with blood serum introduced.
  • the coated test tube and blood can be agitated or shaken as described above.
  • the coating would comprise active ingredient as well as a carrier comprised of any qf the materials known in the art for this purpose.
  • the coating could comprise a readily soluble polymeric substance useful for this purpose, such as a cellulose-based polymeric
  • test tube system shown in Fig. 3 comprises a coated cartridge or substrate 15.
  • the coating on the cartridge 15 contains active ingredient and a suitable carrier.
  • a blood product such as blood serum (not shown)
  • test tube 16 has a stopper 17 so that the blood serum and cartridge can be shaken.
  • test tube 16 could also have a coating (not shown) as described above.
  • Cartridge or substrate 15 may be comprised of any suitable material.
  • substrate 15 may be dissolvable or nondissolvable, sterilizable or inherently sterilized, hydrophilic, or coated or impregnated. It is important that said material not interfere, either physically or analytically, with further processing of the blood product. The actual materials, as well as the amounts to be used, impregnated, or coated, can be readily determined.
  • Fig. 4 comprises a blood bag 20 which can have active ingredient either as powder (not shown) or a coating 21 on the interior surface 22 of the blood bag 20. Said coating can, be continuous or
  • Dissolution of the coating and active ingredient can be enhanced by shaking or other agitation of the blood bag with blood inside.
  • envisioned ratio of the MG compounds administered to other medical containers or hardware is from about 10 ⁇ g to 500 mg/ml of blood, plasma, serum, or other blood product, preferably from about 25 ⁇ g/ml to 200 mg/ml of blood, plasma, serum, or other blood product, more preferably from about 75 ⁇ g/ml to 100 mg/ml of blood, plasma, serum, or other blood product.
  • Examples of other conventional containers or hardware include blood bags, vacutainer tubes. test kit materials, veno claysis kits, rubber gloves, and the like. An exemplary aspect of the invention would be precoated vacutainer tubes.
  • the aforesaid invention need not be limited to treatment of blood products or body sera. Other potential applications or the antiviral and
  • facial, cream as an acne treatment
  • bactericidal bactericidal
  • fungicidal virucidal
  • shampoo, hand lotion athlete's foot medication
  • candies for sore throat, bad breath, recurrent herpes
  • ointment or foam spray for genital herpes legion treatment
  • shaving cream mouth wash; after shave lotions; tooth paste; diaper rash preventer; plasma bag treatment; disposable glove treatment; additive to pasteurized cow milk; additive to blood sample tubes to inactivate HIV and CMV (safety measure for lab technicians); additives for condoms, band-aids, or bandages; additive for paint; or animal treatment for viral infections.
  • CMV safety measure for lab technicians
  • Rubber gloves could be “dusted” on inner and/or outer surfaces with powdered antiviral component according to the invention.
  • the gloves themselves could be comprised of a material, preferably polymeric, containing antiviral component that would release antiviral component upon contact with liquid such as a blood product or other body fluid or derivative thereof.

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  • Health & Medical Sciences (AREA)
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  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
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  • Animal Behavior & Ethology (AREA)
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EP19900917767 1989-06-12 1990-06-11 Reducing the spread of infection by blood handling equipment Withdrawn EP0429645A4 (en)

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CA2001401A1 (en) * 1988-10-25 1990-04-25 Claude Piantadosi Quaternary amine containing ether or ester lipid derivatives and therapeutic compositions
FI912955A (fi) * 1990-06-25 1991-12-26 Res Found Mental Hygiene Antimikroba fettsyrasammansaettningar.
EP0702556B1 (de) * 1993-06-10 2002-10-23 Wake Forest University (phospho)lipide zum bekämpfen einer hepatitis b-infektion
US7135584B2 (en) 1995-08-07 2006-11-14 Wake Forest University Lipid analogs for treating viral infections
US5962437A (en) 1994-08-29 1999-10-05 Wake Forest University Lipid analogs for treating viral infections
US7026469B2 (en) 2000-10-19 2006-04-11 Wake Forest University School Of Medicine Compositions and methods of double-targeting virus infections and cancer cells
US7309696B2 (en) 2000-10-19 2007-12-18 Wake Forest University Compositions and methods for targeting cancer cells
KR100871648B1 (ko) 2001-08-31 2008-12-03 톰슨 라이센싱 조건부 액세스 시스템을 구현하는 방법, 컨텐트를 전송하는 방법 및 그 장치 및 컨텐트를 수신하고 처리하는 방법 및 그 장치
US20050215634A1 (en) * 2003-11-11 2005-09-29 Schlievert Patrick M Regulation of cell membrane-mediated effects
US8796332B2 (en) 2004-08-03 2014-08-05 Regents Of The University Of Minnesota Compositions and methods for controlling infections
EP1833298B1 (de) * 2004-12-17 2013-05-08 Halldor Thormar Stabile konzentrierte antibakterielle emulsionen von monocaprin in wasser
WO2006130529A1 (en) * 2005-05-31 2006-12-07 Pierce Biotechnology, Inc. Extraction of cellular components with fatty acid derivatives
JP2010163397A (ja) * 2009-01-16 2010-07-29 Japan Ecologia Co Ltd 抗菌性組成物

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EP0021504A2 (de) * 1979-06-25 1981-01-07 THE PROCTER & GAMBLE COMPANY Gegenstand zum Gebrauch als Katheter oder dgl.
US4613501A (en) * 1984-12-21 1986-09-23 New York Blood Center, Inc. Inactivation of viruses in labile blood derivatives
WO1988009655A1 (en) * 1987-06-05 1988-12-15 Al Sioufi Habib Method and device for disinfecting biological fluids and container for same
EP0300814A2 (de) * 1987-07-24 1989-01-25 JOHNSON & JOHNSON MEDICAL, INC. Antimikrobische ärztliche Handschuhe
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US4613501A (en) * 1984-12-21 1986-09-23 New York Blood Center, Inc. Inactivation of viruses in labile blood derivatives
US4841023A (en) * 1986-06-25 1989-06-20 New York Blood Center, Inc. Inactivation of viruses in labile protein-containing compositions using fatty acids
WO1988009655A1 (en) * 1987-06-05 1988-12-15 Al Sioufi Habib Method and device for disinfecting biological fluids and container for same
EP0300814A2 (de) * 1987-07-24 1989-01-25 JOHNSON & JOHNSON MEDICAL, INC. Antimikrobische ärztliche Handschuhe
WO1989006124A1 (en) * 1987-12-31 1989-07-13 Research Foundation For Mental Hygiene, Inc. Antiviral and antibacterial activity of fatty acids and monoglycerides

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JOURNAL OF DAIRY SCIENCE, vol. 59, no. 7, July 1976, pages 1203-1214; R.G. JENSEN et al.: "Milk lipoprotein lipases: A review" *
See also references of WO9015601A1 *

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GR900100435A (en) 1991-11-15
WO1990015601A1 (en) 1990-12-27
JPH04501570A (ja) 1992-03-19
FI902821A0 (fi) 1990-06-06
CA2032484A1 (en) 1990-12-13
EP0429645A4 (en) 1992-05-13
NZ233990A (en) 1992-01-29
AU5945590A (en) 1991-01-08
GR1000951B (el) 1993-03-16
BR9006800A (pt) 1991-08-06

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