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WO1990015609A1 - Prophylaxie et traitement d'infections microbiennes avec des phosphoglycerides - Google Patents

Prophylaxie et traitement d'infections microbiennes avec des phosphoglycerides Download PDF

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Publication number
WO1990015609A1
WO1990015609A1 PCT/US1990/003353 US9003353W WO9015609A1 WO 1990015609 A1 WO1990015609 A1 WO 1990015609A1 US 9003353 W US9003353 W US 9003353W WO 9015609 A1 WO9015609 A1 WO 9015609A1
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Prior art keywords
infection
administering
yeast
phosphatidylcholine
group
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PCT/US1990/003353
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English (en)
Inventor
Joseph J. Vitale
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Med-Tal Inc
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Med-Tal Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds

Definitions

  • This invention is in the field of anti-microbial chemotherapy and pertains to a method of preventing or treating infectious disease.
  • GBS Group B Streptococci
  • GBS disease The incidence of GBS disease is estimated at between 2 to 5 cases per 1000 live births. Pass, M.A. (1979) J. Pediatr. 795, 437-443. At highest risk are premature infants, whose birth weight is less than 2500 grams and infants born to mothers with premature rupture of membranes. Fisher, G. W., supra. Susceptibility to and severity of GBS
  • neonates who develop Group B S treptococcal Sepsis usually lack opsonic antibody to their infecting strain.
  • Opsonic antibody is antibody that combines with antigen and facilitates ingestion of the antigen by phagocytes.
  • these neonates usually have impaired polymorphonuclear leukocyte (PMN) function.
  • PMN polymorphonuclear leukocyte
  • GBS disease Susceptibility to GBS disease, like to other infectious diseases, is multi-factorial and impinges on native and acquired immunity which are influenced by the host's genetic constitution, sex, age, and nutritional status. Of the aforementioned factors, there is very little information available as to the role of single or aggregate nutrients on host resistance to GBS disease. Almost any nutritional deficiency or excess may affect adversely one or more components of the immune system. Conversely the same nutrients that impinge on the immune system may also be essential for the multiplication and virulence of certain pathogenic microorganisms.
  • This invention pertains to a method of therapy or prophylaxis of bacterial, yeast, protozoan and viral infections and to novel compositions comprising essentially pure phosphatidyl choline containing only omega-6 fatty acids, particularly only linoleic acid.
  • the method comprises administering , in either therapeutic or prophylactic amounts, one or more of the phosphoglycerides:
  • phosphatidylcholine preferably phosphatidylcholine containing linoleic acid, phosphatidylethanolamine, phosphatidylserine or phosphatidylinositol.
  • the method of this invention is founded upon the discovery that the phosphatidylcholine (PC) - an ubiquitous constituent of biomembranes - protects newborn animals against mortality which usually results from Group B hemolytic S treptococcal infection. As explained, this microorganism is particularly virulent in newborns. In an experimental model of neonatal sepsis in which Group B hemolytic streptococci (GBS) was the causative agent, phosphatidylcholine proved an effective therapeutic agent. PC treatment prevented or delayed the death of newborn rats inoculated with GBS. A single injection of PC significantly increased the number of newborn rats which survived GBS inoculation and significantly prolonged the mean survival time of the entire treated group.
  • PC phosphatidylcholine
  • PC was also effective in prophylaxis, that is prevention, of GBS infection.
  • PC was given prophylactically to pregnant rats, PC reduced mortality in their offspring inoculated with GBS.
  • PC prevented weight loss in post-natal rats by enhancing host defense mechanisms.
  • phosphatidylcholine may have a role as a nutritional supplement or as a practical therapeutic agent, or adjunct, in the treatment and prevention of GBS disease and other infections (e.g. viral, fungal, protistan etc.).
  • GBS disease and other infections e.g. viral, fungal, protistan etc.
  • other phosphoglyceride constituents of biomembranes are likely to act similarly.
  • the phosphoglycerides phosphatidyle thanolamine, phosphatidylserine and phosphacidylinositol may also be useful in combating or preventing bacterial infection.
  • the phosphoglycerides may act by stimulating the hosts immune response to foreign organisms in general, they may be effective therapeutic and prophylactic agents for viral infection.
  • PC and possibly other phosphoglyceride components of biomembranes are believed to protect against the lethal action of bacteria by promoting the clearance of these disease-causing organisms by the reticuloendothelial system (RES) by altering the fluidity, and consequently the function, of the phagocytic cells (i.e., the polymorphonuclear leukocytes and macrophages) which make up the RES.
  • RES reticuloendothelial system
  • This theory is supported by a study involving oral ingestion by humans of species of phosphatidylcholine in which linoleic acid was the primary fatty acid constituent (e.g., soy phosphatidylcholine). The study revealed that the composition and the concentration of arachidonic acid in polymorphonuclear leukocytes from these humans had been modified. This alternation in membrane lipid composition was found to occur in conjunction with an increased immune response.
  • Figure 1 illustrates the opsono-phagocytic activity of PC-treated and untreated neonatal rats infected with GBS.
  • Figure 2 illustrates the increased survival rate of rat pups whose mothers were treated with PC.
  • Figure 3 illustrates the effect of phosphatidyl choline (PC) on infection of murine macrophages.
  • Figure 4 illustrates the effect of PC on intracellular multiplication of RH strain tachyzoites within macrophage vacuoles.
  • Figure 5 illustrates the changes in 20:4 of PMNs before (unstimulated) and after (stimulated) exposure to Candida albicans in four subjects - - two fed PC and two fed placebo. Best Mode of Carrying Our the Invention
  • PC biomembrane phospholipid phosphatidylcholine
  • Prophylactic efficacy of PC was evaluated by administering PC to pregnant rats prior to parturition and then inoculating offspring with GBS.
  • the survival rate of pups delivered by PC-treated mothers was greater than pups delivered by mothers that did not receive PC. (23% of pups from PC-treated mothers survived whereas only 2.5% of pups from untreated mothers survived for 72 hours after infection.)
  • PC also prevents vertical transmission of GBS from mother to fetus. Neonates of infected dams treated with PC were less likely to be bacteremic, that is, harbor viable GBS organisms in their tissues.
  • PC polymorphonuclear leukocytes
  • PMNLs polymorphonuclear leukocytes
  • macrophages a major membrane component
  • RES reticulo-endothelial system
  • PC may also act by modifying surface components of the bacteria. These modifications may result in increased phagocytic uptake of invading organisms by host phagocytic cells or they may result in an abatement of the virulence of micro-organisms.
  • PC-treated animals infected with GBS have a blunted opsono-phagocytic activity. This could mean that PC masks or alters the immunogenic surface receptors of the injected GBS and this results in a diminished type specific antibody response to the organism.
  • PC may have a paradoxical effect of improving PMN function on the one hand and of decreasing B cell function and antibody production on the other hand.
  • a role for PC in the inhibition of lectin mediated blastogenesis has been previously proposed. Chen, S.S. and Keenan, R.M. (1977) Biochem. Biophys. Res. Comm. 79 , 852-858.
  • Phosphatidylcholine belongs to a family of phosphoglycerides which are found almost entirely in cellular membranes as constituents of the lipid bilayer.
  • Phosphoglycerides comprise glycerol phosphate, two fatty acid residues esterified to the hydroxyl groups at carbons 1 and 2 of glycerol and an alcohol component (e.g. choline in phosphatidyl- choline) whose hydroxyl group is esterified to the phosphoric acid. Because of the similarity of structure and function of these compounds, the therapeutic and protective action manifested by PC toward bacterial infection may be common to the group. This is believed to be so particularly for the other major phosphoglycerides, phosphatidyl- ethanolamine, phosphatidylser ine and phosphatidyl- inositol.
  • a preferred embodiment of this invention employs a species of phosphatidylcholine in which linoleic acid (C18:2n-6) is the primary (preferably the only) fatty acid constituent (e.g. soy phosphatidylcholine).
  • Linoleic acid is an omega-6 fatty acid, as opposed to an omega-3 fatty acid (e.g.
  • linoleic acid is the major lipid consumed in conventional Western diets, it is the major fatty acid comprising the phospholipid bilayer of the cell membranes of most people who consume a Western diet.
  • the phosphatidylcholines containing omega-6 fatty acids can be synthesized by adding or replacing fatty acids on carbons 1 and 2 of the glycerol molecule. For example, fatty acids on carbons 1 and 2 of a glycerol molecule can be removed and the phospholipid can be reconstituted in the presence of linoleic acid.
  • phosphatidylcholines containing omega-6 can be isolated from heterogenous preparations of phosphatidylcholines available from commercial sources.
  • phospholipids although comprising only 5-9% by weight, form 40-65% of the outer surface of chylomicrons. Davenport, H.W.,
  • the phosphoglycerides may be administered enterally or parenterally. Enteral administration is the preferred route. As the phosphoglycerides are components of many foods, they may be administered conveniently by ordering a diet which will supply the appropriate amount of the phosphoglycerides.
  • the phospholipid may be given alone in bolus doses as a dietary supplement.
  • compositions may be prepared comprising the phosphoglyceride in a physiologically-acceptable vehicle.
  • a sterile emulsion of the phosphoglycerides in phosphate buffered saline is a suitable composition for infusion.
  • dosage regimens may be optimized according to established principles of pharmacokinetics.
  • the phosphoglycerides may be administered to a patient who has been determined clinically to have contracted a bacterial, yeast or viral infection. Besides being efficacious therapeutic agents in their own right, the phosphoglycerides may be useful adjuncts to conventional therapeutic regimens.
  • phosphatidylcholine may be administered conjunctively with antibiotics or other anti-microbial agents.
  • Prophylactic use of the phosphoglycerides is appropriate in patients who are at risk of contracting bacterial infection.
  • Patients especially susceptible to bacterial infection include premature infants, infants born to mothers with prematurely ruptured membranes and persons whose immune system is suppressed or compromised such as certain cancer patients (e.g. leukemics) or cancer patients undergoing chemotherapy, persons suffering from Acquired Immune Deficiency (AIDS) or the aged.
  • the phosphoglycerides may be administered alone or as an adjunct to other forms of prophylaxis.
  • the phosphoglycerides can be be used with other prophylaxis forms in the treatment of AIDS.
  • Vitamin D3 or its active metabolites such as the hormonal product, 1,25-(OH) 2 D3, (HD) can inhibit Interleukin-2 production and depress T-cell proliferation when T-cells are exposed to mitogen.
  • receptors for HD are not present on resting T- and B-cells but are present on monocytes and malignant T-lymphocytes.
  • proliferation and differentiation occurs with expression of HD receptors.
  • the addition of HD in pico-molar concentrations inhibits the proliferation of activated
  • T-cells may be infected with the Human-Immunodeficient Virus (HIV).
  • HIV Human-Immunodeficient Virus
  • the macrophage is required for T-cell activation and may have an important role not only in promoting the replication of the virus but also in transmitting virus to resting T-cells.
  • a combined therapeutic regimen of both phosphatidylcholine/HD would be of value in mitigating the morbidity associated with the HIV infection.
  • a important mode of prophylaxis of neonatal sepsis is treatment of the mother with a prophylactic agent prior to parturition.
  • a prophylactic agent As described above, maternal administration of PC effectively protects newborns against GBS infection.
  • the phosphoglycerides may be administered prophylactically late in pregnancy, either alone or in conjunction with other prophylactic agents (e.g. antibiotics) in situations of high risk of neonatal infection.
  • prophylactic agents e.g. antibiotics
  • phosphoglycerides are common nutrients, there is minimal risk of toxicity attendant to their administration.
  • common components of foods they can be administered orally and may be given therapeutically by prescribing a diet which provides the desired amount.
  • PC in particular, has the potential for being exploited to the benefit of the host.
  • mammalian tissue free choline participates in four enzyme-catalyzed pathways: oxidation, phosphorylation, acetylation, and base exchange.
  • EXAMPLES Example 1. Therapeutic Effect of PC in Neonatal Sepsis Soy leciuhin, 95% pure, (Unilever Inc., Valardinger, Netherlands) was mixed in phosphate buffered saline (PBS) to a concentration of 250 mg/ml.
  • PBS phosphate buffered saline
  • Lecithin preparation contained 25.84 nanomoles of phosphatidylcholine per 100 ul of mixture as determined by thin layer chromatography.
  • Sprague Dawley outbred pregnant female rats (Charles River) and Lewis pregnant female rats were obtained one week before delivery. The neonatal progeny less than 24 hours old were randomly assigned to groups and entered into the study.
  • the assay was conducted in the following manner: to an 8 ml vial, the following reagents were added: 0.8 ml of KRB buffer, 1.5 ml sterile distilled water, 2.5 ml 1 mM luminol (Kodak), 10 ml whole blood, and finally 150 ul of an overnight culture of GBS Type III washed and adjusted to 1 ⁇ 10 9 c.f.u. per ml to achieve a PMN : particle ratio of 1:3000. Blood from each rat was studies in duplicate; thus two samples from each rat were placed in the scintillation counter. Three background samples with the particle and chemiluminescence mixture were run with each assay.
  • opsono-phagocytic activity of GBS infected Lewis rats was determined fourteen days post infection using whole blood and un-opsonized live GBS as the particle.
  • Depicted in Figure 1 are the chemiluminescence (CL) values for rats that were infected and received either saline or PC and uninfected rats that received only PC. Animals that received PC had a lower mean CL response than saline treated controls but both had a greater response than uninfected animals.
  • Example 2 Prophylactic Effect of PC
  • the present study was designed to evaluate the prophylactic effect of PC given to pregnant Sprague Dawley dams on GBS infection in their offspring.
  • GBS was isolated from these animals and their unborn pups. Seventy-four pups were born to 8 PC-treated animals; fifty-one pups to the 5 remaining controls. Pups were sacrificed and cultured at 4-8 hour intervals following birth. GBS was isolated from liver, spleen, blood or brain in 15/74 (20%) pups in PC-treated group. In contrast, 19/51 (37%) of saline treated groups had positive cultures.
  • a rat litter (N-13) was randomly assigned to receive either a single i.p. injection of PC soy lecithin (see Example 1, above) or 500 mg/kg of an equivalent control injection of phosphate buffered saline (PBS). Pups were allowed to nurse and weighed every two to three days.
  • PC soy lecithin see Example 1, above
  • PBS phosphate buffered saline
  • mice normal CD-1 female mice (8 weeks-old) were inoculated intraperitoneally with PBS (control), high dose PC (10mg/kg) or low dose PC (5mg/kg). The mice were sacrificed seven days later.
  • Adherent peritoneal macrophage monolayers prepared from each group were challenged with RH strain toxoplasma tachyzoites (zero time) at a multiplicity of infection ratio of 1:1 (parasite: macrophage). At 1 and 18 hours after zero time, monolayers were fixed and stained, and then assessed for percent infection (number of infected macrophages/total number of macrophages counted (200) ⁇ 100). Results
  • mice were treated with either PBS (control), high dose PC (10mg/kg) or low dose PC (5mg/kg) according to the protocol outlined in 5A.
  • macrophage monolayers were prepared from each group, then infected with RH strain tachyzoites (zero time) at a multiplicity of infection ratio of 1:1 (parasite:macrophage).
  • monolayers were fixed, stained and assessed by light microscopy for evidence of intracellular multiplication of toxoplasma within macrophage vacuoles. Data are expressed as the percent of infected macrophages with 0, 1 and 3 parasite divisions per vacuole for each group. Results
  • control group revealed significantly (P 0.01) fewer percent infected macrophages ⁇ SD with no parasite divisions (22.5 ⁇ 0.71) than either the high dose PC group (54.5 ⁇ 6.36) or the low dose PC group (45.5 ⁇ 0.71). However, the control group had significantly (P 0.05) more percent injected macrophages with 1 (77.5 ⁇ 0.71) or 3 (63.00 ⁇ 8.49) parasite divisions compared with the respective values for the high dose PC group ( 1:45.5 ⁇ 6.36; 3:28.5 ⁇ 3.54) and the low dose PC group ( 1:54.5 ⁇ 0.71; 3:45.5 ⁇ 2.12). (See Figure 4.) (The significance of the differences between test and control groups was determined by the t-test for summary data.) Summary of Example 6
  • Peritoneal macrophages obtained from CD-1 mice 7 days after treatment with PC either at high dose or low dose exhibited: (a) significantly reduced infection rates 18 hours after in vitro challenge with RH strain toxoplasma tachyzoites compared with the controls, and (b) significantly reduced intracellular replication of the parasite 18 hours after in vitro infection compared with the controls.
  • Table VIII indicates that circulating PMNs that migrated to the sponge were not affected by the PC and that if PC leaked out of the sponge, it had no effect on PMNs isolated from blood. No differences in NBT reduction by PMNs or macrophages were observed between PC and PBS treatments.
  • Table IX demonstrates that rats pretreated with PC had significantly more active PMNs and macrophages compared to the PBS treated animals.
  • Phagocytized Candida albicans yeast particles were also determined according to accepted procedures.
  • PC increases PMN phagocytosis and the percent of phagocytized Candida albicans killed. Effect of PC on Arachidonic Acid Concentrations in PMNs Before and After Exposure to Candida Albicans and Relation to Phagocytosis/Killing
  • Figure 5 depicts the concentration (Units, relevant to a standard) of 20:4 in PMN before
  • PC-95 is a mixture of 95% phosphatidyl choline and 5% phosphatidyl ethanolamine. Blood samples were drawn pre-supplementation, and at 48 hours and 72 hours post-supplementation for analysis of PMN killing of C. albicans.
  • PC-95 may be a promising treatment both for producing clinical improvement and reducing the financial strain on the medical care system.
  • Linoleic Acid as the Fatty Acid
  • PMNLs were isolated by the method of Boyum, A., Scand J Clin Invest 21: 77-89 (1968), and PMNL phagocytosis was measured by the method of Bridges, C. G., et al., NEED JOURNAL 42: 226-33 (1979), which involves inhibition of H-uridine uptake.
  • PMNL killing of Candida albicans was determined by the method of Levitz, S. M., and Diamond, R. D., J.
  • the GLC was equipped with a Supelco 2330 fused silica capillary column (30 meters ⁇ 0.25 mm I.D., 0.2 micron film) and a flame ionization
  • pathogen - - including HIV (AIDS virus) - - replication occurs within the cell by altering receptor sites, rigidity (or fluidity) and function of cells.
  • pathogen - - including HIV (AIDS virus) - - replication occurs within the cell by altering receptor sites, rigidity (or fluidity) and function of cells.
  • the malaria parasite replicates within the red cells by causing perturbations in the lipid membrane of the RBC both in a qualitative and quantitative sense as does
  • Toxoplasma gondi in macrophages plays a key role in amplifying both cell mediated and humoral responses to infection and in disposing of foreign and infected cells.
  • n 30 18.89 ⁇ 1.09 26.01 ⁇ 1.15 28.78 ⁇ 1.52- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
  • n 30 20.67 ⁇ 1.69
  • n 30 13.61 ⁇ 0.76 20.96 ⁇ 1.33 22.49 ⁇ 1.29 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
  • n 30 8.91 ⁇ 0.78 14.89 ⁇ 1.30 15.44 ⁇ 1.16 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
  • n 40 31.98 ⁇ 2.48 42.40 ⁇ 2.31 36.02 ⁇ 2.58 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
  • Linoleic (18:2 n6) 65.9 Linolenic (18:3 n3) 6.5

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
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  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Les phosphoglycérides sont des agents thérapeutiques et prophylactiques efficaces contre les infections bactériennes, les infections fongiques par des protistes et les infections virales. Ces phosphoglycérides sont utilisés dans divers contextes thérapeutiques. Les procédés thérapeutiques décrits comprennent l'utilisation de phosphoglycérides afin de combattre des infections bactériennes, des infections fongiques par des protistes et des infections virales. Ces phosphoglycérides peuvent être utilisés en thérapie et en prophylaxie de personnes souffrant du SIDA. Un phosphoglycéride préféré est une espèce de phosphatidylcholine dans laquelle l'acide linoléique est le principal acide gras.
PCT/US1990/003353 1989-06-15 1990-06-13 Prophylaxie et traitement d'infections microbiennes avec des phosphoglycerides Ceased WO1990015609A1 (fr)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0591303A4 (en) * 1991-06-24 1994-09-21 Adelaide Children S Hospital Methods and compositions for treating malaria and other diseases
WO2001002005A3 (fr) * 1999-06-30 2001-07-05 Isis Innovation Induction de la tolerance immunitaire
WO2004068969A1 (fr) * 2003-02-05 2004-08-19 N.V. Nutricia Composition enterale pour la prevention et/ou le traitement d'une septicemie
EP1401402A4 (fr) * 2001-05-29 2006-12-06 Tap Pharmaceutical Prod Inc Amelioration de la biodisponibilite orale de preparation non emulsionnee d'esters de prodrogues avec de la lecithine

Citations (5)

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Publication number Priority date Publication date Assignee Title
DE1910716A1 (de) * 1968-03-04 1969-10-02 Stanley Drug Products Inc Antimikrobielles Arzneimittel und dessen Verwendung
EP0100964A2 (fr) * 1982-07-31 1984-02-22 Reifenrath, Rainer, Dr. Produit pharmaceutique pour le traitement et la prophylaxie d'infections, de la toux et d'affections obstructives des voies respiratoires, ainsi que son procédé de préparation
WO1987001592A1 (fr) * 1985-09-17 1987-03-26 Yeda Research And Development Company, Ltd. Inactivation d'un virus
US4666893A (en) * 1983-02-15 1987-05-19 St. Thomas Institute Methods of inducing resistance to bacterial and viral infections
WO1989003220A1 (fr) * 1987-10-06 1989-04-20 Houston Biotechnology Incorporated Utilisation de phosphatidyle pour le traitement de maladies virales

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1910716A1 (de) * 1968-03-04 1969-10-02 Stanley Drug Products Inc Antimikrobielles Arzneimittel und dessen Verwendung
EP0100964A2 (fr) * 1982-07-31 1984-02-22 Reifenrath, Rainer, Dr. Produit pharmaceutique pour le traitement et la prophylaxie d'infections, de la toux et d'affections obstructives des voies respiratoires, ainsi que son procédé de préparation
US4666893A (en) * 1983-02-15 1987-05-19 St. Thomas Institute Methods of inducing resistance to bacterial and viral infections
WO1987001592A1 (fr) * 1985-09-17 1987-03-26 Yeda Research And Development Company, Ltd. Inactivation d'un virus
WO1989003220A1 (fr) * 1987-10-06 1989-04-20 Houston Biotechnology Incorporated Utilisation de phosphatidyle pour le traitement de maladies virales

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
JRCS Medical Science, Volume 12, 1984, D.S. WALSH et al.: "Anti-Dermonecrotic Activity of Various Phospholipids on Staphylococcal alpha-Toxin", pages 562-563 *
JRCS Medical Science, Volume 13, 1985, J.E. SLAWINSKI et al.: "Effects of Purified Bovine Lecithin on Klebsiella Pneumoniae infections in Mice", pages 742-743 *
JRCS Medical Science, Volume 9, 1981, M.C. SOWAR et al.: "The Prophylactic Effect of a Phosphatidylcholine on Staphylococcus Aureus Infections in Swiss Albino Mice", page 459 *
JRCS Medical Science, Volume 9, 1981, M.L. KABONGA MUAMBA et al.: "Use of Phosphatidylcholine for Reduction of Inflammatory Reactions Induced by Intradermal Injection of Propionibacterium Acnes in Rabbits", page 1017 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0591303A4 (en) * 1991-06-24 1994-09-21 Adelaide Children S Hospital Methods and compositions for treating malaria and other diseases
US5604258A (en) * 1991-06-24 1997-02-18 Women's And Children's Hospital Adelaide Methods for treating malaria and other diseases
WO2001002005A3 (fr) * 1999-06-30 2001-07-05 Isis Innovation Induction de la tolerance immunitaire
EP1401402A4 (fr) * 2001-05-29 2006-12-06 Tap Pharmaceutical Prod Inc Amelioration de la biodisponibilite orale de preparation non emulsionnee d'esters de prodrogues avec de la lecithine
WO2004068969A1 (fr) * 2003-02-05 2004-08-19 N.V. Nutricia Composition enterale pour la prevention et/ou le traitement d'une septicemie

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