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WO2006096937A1 - Utilisation du silicate de cuivre pour controler les infections a l’herpes - Google Patents

Utilisation du silicate de cuivre pour controler les infections a l’herpes Download PDF

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Publication number
WO2006096937A1
WO2006096937A1 PCT/AU2006/000363 AU2006000363W WO2006096937A1 WO 2006096937 A1 WO2006096937 A1 WO 2006096937A1 AU 2006000363 W AU2006000363 W AU 2006000363W WO 2006096937 A1 WO2006096937 A1 WO 2006096937A1
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WO
WIPO (PCT)
Prior art keywords
hsv
copper silicate
copper
herpes virus
infection
Prior art date
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Ceased
Application number
PCT/AU2006/000363
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English (en)
Inventor
John Dawson
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Conve Ltd
Original Assignee
Conve Ltd
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Filing date
Publication date
Priority claimed from AU2005901294A external-priority patent/AU2005901294A0/en
Application filed by Conve Ltd filed Critical Conve Ltd
Priority to AU2006225096A priority Critical patent/AU2006225096A1/en
Priority to CA002600935A priority patent/CA2600935A1/fr
Priority to EP06705032A priority patent/EP1858531A1/fr
Publication of WO2006096937A1 publication Critical patent/WO2006096937A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • A61K33/34—Copper; Compounds thereof
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses

Definitions

  • the present invention relates to the use of copper silicate for treating and preventing Herpes virus (HV) infections and diseases and in particular diseases caused by HSV- 1 or HSV-2 such as herpes and Varicella zoster (VZV) such as shingles.
  • HV Herpes virus
  • HSV- 1 or HSV-2 such as herpes and Varicella zoster
  • VZV Varicella zoster
  • the present invention also relates to copper silicate compositions specifically adapted to treat HV infections.
  • Herpes simplex virus enters the host by direct contact, is spread to a target tissue only, spreads within the host via neuronal axonal flow, targets the dorsal root ganglia and after recovery of the host from an acute infection, remains latent in the targeted tissue.
  • HSV disrupts host cell molecular functions and host cellular structure and is manifested clinically as host cellular death, resulting in shallow, painful vesicular ectodermal lesions or by hemorrhagic encephalitic necrosis of the brain.
  • Target tissues for HSV are the skin or mucous membranes usually derived from embryonic ectoderm: mouth, skin, vagina, conjunctiva, cornea, etc.
  • the virus enters the host cell by direct mucosal contact or by direct contact of abraded skin. In the skin the virus replicates in epithelial cells and then enters local sensory neurons. The virus travels to the dorsal root ganglia via retrograde axonal flow where it establishes permanent residency.
  • latency a state in which the viral lytic genes are silenced and only the latency locus is transcriptionally active. Although latent most of the time, it reactivates intermittently, travels down the sensory nerve and causes vesicular eruptions at or near the site of initial invasion. Alternatively the virus may invade the CNS and cause encephalitis.
  • HSV herpes simplex Type 1 seroprevalence for men and women has decreased from 75.3 and 80.6% in 1973 to 54.4 and 59.6%, respectively in 1993 and where Herpes simplex Type 2 (HSV-2) seroprevalence has decreased from 10.2 and 9.9% in 1973 to 1.8 and 1.2%, respectively in 1993, to quite high in Africa where all adult study groups have a high HSV-1 seroprevalence of >80%.
  • HSV infects more than 50% of the adult population, but some infections may be unrecognized. About half of these develop clinical manifestations of the disease. It's most significant manifestations are keratitis, genital lesions and labial vesicular lesions ("cold sores").
  • HSV-1 infection A common manifestation of HSV-1 infection is cold sores.
  • HSV-1 also causes herpes keratitis (cornea). This disease is identified by a typically unusual dendritic-patterned corneal ulcer that tends to be recurrent and very often leads to scarring with a reduction of vision, sometimes to the level of legal blindness.
  • HSV-1 also causes herpes labialis, peri-orbital, peri-oral, peri-nasal skin eruptions and, in older patients, the virus has been associated with herpes zoster ("shingles") infection of the upper trunk.
  • HSV-2 causes the most prevalent sexually transmitted disease in the United States and visits to physicians for genital herpes simplex virus infection continue to increase. As many as 30 million Americans are infected with HSV-2. About half of these carriers are symptomatic. The clinical manifestations range from mild genital inflammation to severe, very painful, vesicular lesions and ulceration. Systemic involvement in the most severe cases may include hepatitis. Brain damage and death often are the result of HSV-2 acquired by a newborn infant as it passes through an infected birth canal. HSV-2 can also cause cold sores but this is relatively uncommon.
  • VZV Varicella-zoster virus
  • VZV reactivates much less often than HSV — in association with waning T-cell immunity — usually causing only one lifetime episode of herpes zoster (shingles). Nevertheless, VZV causes more severe damage to the nerve and dorsal root ganglia than HSV, leading to pain and often neural dysfunction. Prolonged pain may result from scarring of neural tissue.
  • Herpes zoster can develop at any age, but the highest incidence is after 60 years. Overall, it occurs in 20% of the population, with more than one recurrence in 4%.
  • the present invention seeks to overcome the above problems by providing a safe, relatively inexpensive and effective treatment for viral skin diseases such as those caused by HSV and VZV.
  • the present invention provides for the use of copper silicate to control Herpes virus (HV).
  • HV Herpes virus
  • the present invention also provides a method of treating a HV infection in a subject, the method comprising the step of administering to said subject an effective amount of copper silicate.
  • the present invention further provides for the use of copper silicate for preparing a medicament for treating the clinical manifestations of HV infections such as cold sores (predominantly caused by HSV-1) or the sores associated with genital herpes (predominantly caused by HSV-2).
  • the present invention still further provides a method of treating or preventing HV infection in a subject, the method comprising the step of repeatedly topically administering an effective amount of copper silicate.
  • the copper silicate may be used as part of combination therapy.
  • the present invention also provides a method of treating or preventing HV infection in a subject, the method comprising the step(s) of topically administering an effective amount of copper silicate and (ii) administering to said subject an effective amount of at least one other anti-viral agent or an effective amount of at least one anaesthetic.
  • the present invention also provides for the use of copper silicate for preparing a medicament for treating or preventing HV infection or a disease or disorder caused by HV.
  • the present invention further provides a composition adapted for topical administration to a site of HV infection comprising an anti-viral effective amount of copper silicate.
  • Figure 1 is a graph comparing the anti-viral activity of the first copper silicate formulation and a copper sulfate solution
  • Figure 2 is a graph depicting the anti-viral activity of different concentrations of the first copper silicate formulation over time
  • Figure 3 is a graph comparing the anti-viral activity of the first copper silicate formulation and a copper sulfate formulation
  • Figure 4 is a graph depicting the anti-viral activity of a second copper silicate formulation
  • Figure 8 is a graph depicting the cell toxicity of a copper silicate formulation according to one embodiment of the present invention in comparison to copper sulfate. Viability in % was assessed after 30 minute exposure to Cu (750-0.00125 ppm).
  • the present invention provides for the use of copper silicate to control herpes virus (HV).
  • HV herpes virus
  • control herpes virus and similar phrases such as “control herpes virus” means one or more of the following: at least reducing the number of viable viruses; at least reducing viral replication; and at least reducing the clinical manifestations of HV infection such as reducing the number or size of lesions, reducing the pain associated with a clinical outbreak and/or reducing the healing time associated with the lesion.
  • HV includes HSV such as Herpes simplex virus 1 (HSV-1), Herpes simplex virus 2 (HSV-2), Varicella zoster virus (VZV) and closely related viruses that cause similar infections/diseases in humans such as other members of the Alphaherpesvirinae subfamily.
  • HSV Herpes simplex virus 1
  • HSV-2 Herpes simplex virus 2
  • VZV Varicella zoster virus
  • closely related viruses that cause similar infections/diseases in humans such as other members of the Alphaherpesvirinae subfamily.
  • the present invention also provides a method of treating a HV infection in a subject, the method comprising the step of administering to said subject an effective amount of copper silicate.
  • HV infection includes (i) clinical manifestations of HV infection in epithelial - derived tissues (mucous membrane or dermal origin) ; and (ii) sites where it is apparent that a clinical manifestation is likely to appear.
  • Target tissues for HV are the skin or mucous membranes usually derived from embryonic ectoderm: mouth, skin, vagina, conjunctiva and cornea.
  • Clinical manifestations include lesions e.g. cold sores and the lesions associated with genital herpes.
  • Particular disorders associated with HSV-1 infection include: gingivostomatitis, genital and other cutaneous lesions, herpes keratitis (cornea), herpes labialis, peri-orbital, peri-oral, peri-nasal skin eruptions, keratoconjunctivitis, retinitis, oesophagitis, pneumonitis, hepatitis, meningitis, adult and neonatal encephalitis, myelitis, erythema multiforme.
  • HSV-2 infection is associated with genital herpes with clinical manifestations ranging from mild genital inflammation to vesicular lesions and ulceration, genital and other cutaneous lesions, oesophagitis, pneumonitis, hepatitis, meningitis, adult and neonatal encephalitis, myelitis, erythema multiforme.
  • Herpes varicella zoster virus is associated with chicken pox and shingles.
  • the copper silicate is preferably applied at a site of visible HV infection. For example, where a lesion exists or where it is apparent that a lesion will soon appear. In this regard, prior to the appearance of a cold sore, there may be localized reddening, tingling, itchiness and/or swelling that is indicative of HV infection.
  • the present invention also provides for the use of copper silicate for preparing a medicament for treating the clinical manifestations of HV infections such as cold sores (predominantly caused by HSV-1) or the sores associated with genital herpes (predominantly caused by HSV-2).
  • the copper silicate has superior anti-viral activity against HSV-1 relative to other copper salts such as copper sulfate. It is also expected that the copper silicate products will have greater efficacy relative to other anti-virals including topicals for treating cold sores.
  • the copper silicate may be administered in a variety of ways but is preferably topically administered.
  • the term “topical” and variants such as “topically” means application to a localized area of the body and/or to the surface of a body part and includes administration to the lips or mouth area, vagina (such as intra-vaginally) and surrounding areas, penis and surrounding areas and to mucous membranes.
  • Topical administration may be achieved in any one of a number of ways.
  • the copper silicate is administered by painting, wiping, rubbing, dabbing or spraying.
  • topical administration may be achieved by applying the copper silicate using a means for dispensing an effective amount of copper silicate.
  • Dispensing means can be varied and include slow release carriers and materials impregnated with copper silicate such as plasters, patches, bandages, cotton wool and gauze.
  • the dispensing means is adapted to deliver the copper silicate over a predetermined time and/or at a predetermined dose.
  • the amount of copper silicate administered in the method of the present invention will be sufficient to effectively treat the infection and thus will necessarily vary depending at least on the severity, type and location of the infection, the strength of the copper silicate and the manner in which individual patients respond to the treatment.
  • a copper silicate composition containing about 0.1 -10% wt copper is administered.
  • the precise dose administered for a particular disorder may be determined by suitable qualified medical practitioner.
  • the frequency with which, and the duration for which, the copper silicate is applied will be sufficient to effectively treat or prevent the infection and thus will also vary depending at least on the severity and type of infection, the strength of the composition and the manner in which individual patients respond to the treatment.
  • the copper silicate is applied at least one, two, three or up to 5-10 times a day for at least 1 to 6 days or 1 , 3, 6 or 12 weeks. Alternatively, it may be applied once every 2 - 14 days for as long as necessary to treat or prevent infection.
  • the dosage regime for treating a particular disorder may be determined by suitable qualified medical practitioner.
  • the present invention also provides a method of treating or preventing HV infection in a subject, the method comprising the step of repeatedly topically administering an effective amount of copper silicate.
  • the present invention also provides a method of treating or preventing HV infection in a subject, the method comprising the step(s) of topically administering an effective amount of copper silicate and (ii) administering to said subject an effective amount of at least one other anti-viral agent.
  • the other anti-viral agent may be varied and include systemic or topical agents or an agent selected from the list comprising: Aciclovir, Valaciclovir, Penciclovir, Famciclovir, Ganciclovir.
  • the copper silicate may also be combined with anaesthetics.
  • the present invention also provides a method of treating or preventing HV infection in a subject, the method comprising the step(s) of topically administering an effective amount of copper silicate and (ii) administering to said subject an effective amount of at least one anaesthetic.
  • the anaesthetic is a local anaesthetic.
  • the local anaesthetic is of the ester type such as cocaine, procaine, tetracaine (amethocaine) and chloroprocaine, or the amide class such as lidocaine, prilocaine, mepivacaine, ropivacaine, levobupivacaine and bupivacaine.
  • the present invention also provides for the use of copper silicate for preparing a medicament for treating or preventing HV infection or a disease or disorder caused by HV.
  • the present invention also provides a composition adapted for topical administration to a site of HV infection comprising an anti-viral effective amount of copper silicate.
  • the form of the topical composition of the present invention may also be varied provided it retains its anti-viral properties.
  • the composition is a solution.
  • the composition may also be in solid form provided it is properly formulated.
  • the composition could comprise copper silicate in the form of a micronized solid.
  • the copper silicate When the copper silicate is provided in the form of a solution, it preferably is provided as an aqueous acidified solution. Acidified solutions are particularly preferred because copper silicate is more soluble and stable at acidic pH. Particularly preferred pHs are 3-6, 4-6 and 5-6. In one example, the copper silicate is prepared according to the methods described and claimed in US patent 5,474,972.
  • composition adapted for topical administration may be in the form of any one of the following: solution, lotion, suspension, emulsion, cream, gel, ointment, liniment and salve. Particularly preferred forms are ointments, creams or gels as these are more amenable to administration at the sites of HV infection.
  • Ointments generally are prepared using either (1) an oleaginous base, i.e., one consisting of fixed oils or hydrocarbons, such as white petroleum or mineral oil, or (2) an absorbent base, i.e., one consisting of an anhydrous substance or substances that can absorb water, for example anhydrous lanolin.
  • an oleaginous base i.e., one consisting of fixed oils or hydrocarbons, such as white petroleum or mineral oil
  • an absorbent base i.e., one consisting of an anhydrous substance or substances that can absorb water, for example anhydrous lanolin.
  • Creams are oil/water emulsions. They consist of an oil phase (internal phase), comprising typically fixed oils, hydrocarbons and the like, waxes, petroleum, mineral oil and the like and an aqueous phase (continuous phase), comprising water and any water-soluble substances, such as added salts.
  • the two phases are stabilised by use of an emulsifying agent, for example, a surface active agent, such as sodium lauryl sulfate; hydrophilic colloids, such as acacia colloidal clays, veegum and the like.
  • an emulsifying agent for example, a surface active agent, such as sodium lauryl sulfate; hydrophilic colloids, such as acacia colloidal clays, veegum and the like.
  • the copper silicate may be added to the water phase prior to formation of the emulsion, in an amount to achieve the desired concentration.
  • Gels comprise a base selected from an oleaginous base, water, or an emulsion- suspension base.
  • a gelling agent that forms a matrix in the base, increasing its viscosity.
  • gelling agents are hydroxypropyl cellulose, acrylic acid polymers and the like.
  • the copper silicate may be added to the formulation at the desired concentration at a point preceding addition of the gelling agent.
  • Excipients that can be incorporated into the gel, ointments and lotions of the present invention include: isopropyl myristate NF, trolamine NF, SD alcohol 40 (20%), white petrolatum USP, lanolin alcohols NF, mineral oil USP, polyvinyl alcohol gel, cetostearyl alcohol NF, lactic acid USP, sodium hydroxide USP, polysorbate 60 USNF, Cetyl alcohol USP, Mono- & Di- glycerides USNF, titanium dioxide calcium stearate, dextran, polyoxyl 40 stearate, methylparaben, propylene glycol, sodium lauryl sulfate, polyethylene glycol (PEG) base, synthetic beeswax (B wax), calcium acetate, purified water USP and similar products. These excipients serve a variety of functions as carriers, vehicles, diluents, binders, preservatives, buffers, pH adjusters, emulsifiers and other
  • Dosage forms of the invention for use in treating female genital manifestations of HSV infections, especially HSV-2, are prepared in dosage forms for vaginal insertion including vaginal suppositories, gels, creams and tablets.
  • These preparations optionally may include one or more of the following suitable and pharmaceutically acceptable excipients, including but not limited to: isopropyl myristate NF, mineral oil USP, stearyl alcohol NF, benzoic acid USP, pegoxyl 7 stearate, methylparaben, propylparaben, propylene glycol, butylated hydroxyanisole, coconut or palm kernel oil triglycerides, polysorbate 60 or polysorbate 8, peglicol 5, PEG-100 stearate and sorbitan monostearate, calcium lactate, hydroxypropyl methylcellulose, polysaccharide carrageenan, corn starch, lactose, calcium lactate, silicon dioxide and purified water USP.
  • the topical formulations of the present invention may also be adapted to be delivered to the eye(s) of a subject.
  • the eye drop dosage form of the invention will optionally include one or more suitable and pharmaceutically acceptable inactive excipients, including but not limited to: preservatives from a group including benzalkonium chloride, methylparaben, edetate disodium, thimersol, chlorbutanol; buffers from a group including sodium citrate, potassium chloride, magnesium chloride, sodium acetate, citric acid, sodium lactate; vehicles from a group including polyvinyl alcohol, hydroxy methylcellulose, cetyl alcohol, carboxymethylcellulose, hydroxy-propylenemethyl cellulose; pH adjusters from a group including sulfuric acid, hydrochloric acid, sodium hydroxide, monosodium or disodium phosphate; purified water USP; poloxamer 407 or 188, polysorbate 80; polyoxyethylene polyoxypropylene compound; mineral oil USP.
  • compositions of the present invention may be produced by dissolving or combining the copper silicate in an aqueous or non-aqueous carrier.
  • aqueous or non-aqueous carrier any liquid, cream, or gel, or similar substance that does not appreciably react with the copper silicate or any other active ingredient that may be introduced and which is non-irritating is suitable.
  • composition of the present invention may further comprise an auxiliary agent such as any one or more of: preservatives, stabilizers, emulsifiers, wetting agents, fragrances, colouring agents, odour controllers and thickeners such as natural gums.
  • auxiliary agent such as any one or more of: preservatives, stabilizers, emulsifiers, wetting agents, fragrances, colouring agents, odour controllers and thickeners such as natural gums.
  • the concentration of the copper in the composition may be varied depending at least on the severity and type of infection that the composition is to be used to treat or prevent. However, preferably, the concentration of the copper is approximately 0.01 - 10%. More preferably, the copper concentration is to a final concentration of approximately 0.1 - 5 % or 0.2 - 3%. In one particular form, the concentration of copper is to a final concentration of about 0.22%.
  • Copper silicate is made in situ by a combination of copper sulfate, and sodium silicate in an acidic solution. This solution can then be formulated further to solutions, creams, gels, etc as appropriate. As a result of the "in situ" production of the copper silicate, the contents of the copper silicate formulations listed here do not specifically contain "copper silicate" as one of the starting ingredients. Nonetheless, the copper silicate is present due to the reaction of the copper sulfate and the sodium silicate under the specified conditions.
  • This cream formulation is made in two steps, first by production of a concentrated copper silicate solution (I) that is then immediately on formulated into the final copper silicate cream.
  • Example 1 Anti-viral activity of copper silicate (Formulation A) compared to copper sulfate
  • HSV-1 was exposed, separately to Formulation A and a copper sulfate solution (each over a range of 175 - 1400 ppm Cu) for 30 min.
  • the HSV/copper mixtures were diluted and layered onto the cell monolayer. After 1 hour the mixture was washed away and the cells incubated to allow plaques to form. Plaque numbers were reported as a percentage of the control.
  • Copper silicate Formulation A began to kill HSV-1 at 600 ppm Cu and at 700 ppm the kill rate was >90% ( Figure 1). By comparison, under these conditions, copper sulfate was still ineffective at 1400 ppm Cu ( Figure 1).
  • HSV 1 The clinical isolate of HSV 1 was incubated with copper silicate (Formulation A) dilutions in the same way as example 1. After 30 min, 60 min and 120 min the mixture was washed away and the cells incubated to allow plaques to form. Plaque numbers were reported as a percentage of the control.
  • Formulation A A formulation similar to Formulation A but without the silicate component (Formulation C - effectively a mixture of copper sulfate and acetic acid in solution) was made and tested against Formulation A.
  • the concentration used in the testing of both formulations was 700ppm Cu and the exposure times were 0- 120 min in 30 min intervals.
  • HSV-1 was exposed to Formulation B at various copper concentrations for 60 min in a similar protocol to that used for Example 1.
  • Vera cells were grown to passage 25 and frozen with DMSO (dimethylsulfoxide). Reserve stocks were frozen at passage 24 to allow for extra stocks to be rapidly grown if needed. The cells were frozen and random samples were tested for viability. The stocks were shown to have good viability. The cells were used for the plaque assay at passage 27.
  • DMSO dimethylsulfoxide
  • HSV1 and HSV2 as well as acyclovir resistant HS V2 were obtained from ECACC (European Collection of Cell Cultures) and grown up to produce 50 mL of each virus in a cell free medium. The final concentration of the virus in the initial stock aliquots were as follows:
  • Solutions of copper silicate and copper sulfate were supplied at a concentration of 2,800 ppm copper and a pH of approximately 4.
  • the copper solutions required dilution to a maximum working concentration of 1 ,000 ppm and neutralisation of the acidity. Dilution and neutralisation were achieved by using Tris
  • the viral particles for HSV1 , HSV2, and HSV2ACR were thawed and mixed at appropriate pfu/ml with the copper solutions at final copper concentrations of 750, 400, 200 100, 50, 25, and 0 ppm of copper to produce between 10 and 250 pfu per 24 well plate after dilution.
  • the copper solutions and the viruses were incubated together for 30 minutes.
  • the copper treated HSV was then diluted 1 :500 to avoid toxicity on the Vera cells and plated on 24 well plates at concentrations between 10 to 250 pfu/well.
  • the 24 well plates contained a monolayer of Vero cells in a supporting media.
  • the resulting 500 fold dilution of the copper solutions took the concentration of copper down to 1.5, 0.8, 0.4, 0.2, 0.1 , 0.05 and 0 ppm in 24 well plates.
  • Dimethyl cellulose (DMC) was added to the wells to help identify plaque formation.
  • the plates were then incubated for 3 days to allow HSV plaque formation. Following incubation the fluid over the Vera cells was washed off and the Vera cells stained with crystal violet in 4% paraformaldehyde to inactivate the virus and identify defects in the Vero cell monolayer caused by focal HSV replication (virus plaque). Plaques were counted with 5 fold digital magnification of each well after scanning of stained 24 well plates. There were 7 solutions for each viral strain and each solution was duplicated 4 times on 24 well plates.
  • Each plaque assay was repeated at least 8 times.
  • the cytotoxic effect of copper compounds was tested on Vero cells prior to plaque reduction assays using the CellTiter-BlueTM (Promega) Cell viability assay, followed by colorimetric analysis in 96 well plates.
  • 1 :500 diluted Cu solutions prior to plaque assay showed minimal cytotoxicity allowing for read-out of plaque assays at concentrations of 2 to 1.5 ppm (1000 ppm to 750 ppm Cu-virus solutions).

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Abstract

L’invention concerne l’utilisation de silicate de cuivre pour traiter et prévenir les infections et maladies liées au virus de l’Herpès (HV), et en particulier les maladies causées par le HSV-1 ou le HSV-2, comme l’herpès et l’encéphalite zostérienne (VZV) telle que le zona. L’invention concerne également des compositions de silicate de cuivre spécifiquement adaptées au traitement des infections HV.
PCT/AU2006/000363 2005-03-16 2006-03-16 Utilisation du silicate de cuivre pour controler les infections a l’herpes Ceased WO2006096937A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU2006225096A AU2006225096A1 (en) 2005-03-16 2006-03-16 Use of Copper Silicate for the Control of Herpes Infections
CA002600935A CA2600935A1 (fr) 2005-03-16 2006-03-16 Utilisation du silicate de cuivre pour controler les infections a l'herpes
EP06705032A EP1858531A1 (fr) 2005-03-16 2006-03-16 Utilisation du silicate de cuivre pour controler les infections a l herpes

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AU2005901294A AU2005901294A0 (en) 2005-03-16 Use of Copper Silicate for the Control of HSV Infections
AU2005901294 2005-03-16

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WO2006096937A1 true WO2006096937A1 (fr) 2006-09-21

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014151350A1 (fr) * 2013-03-15 2014-09-25 Cda Research Group, Inc. Traitements topiques par cuivre ionisé et procédés de préparation de traitements topiques par cuivre ionisé utilisés dans des zones anatomiques variées du corps
US9107811B2 (en) 2005-06-20 2015-08-18 Sci-Chem International Pty. Ltd. Composition for treating skin lesions
CN105407726A (zh) * 2013-03-15 2016-03-16 Cda研究集团股份有限公司 身体的皮肤病区域中的局部铜离子治疗物
EP3003247A4 (fr) * 2013-03-15 2017-01-04 CDA Research Group, Inc. Traitements topiques aux ions cuivre
US10813948B2 (en) 2013-03-15 2020-10-27 Cda Research Group, Inc. Methods of treatment using topical copper ion formulations
US11000545B2 (en) 2013-03-15 2021-05-11 Cda Research Group, Inc. Copper ion compositions and methods of treatment for conditions caused by coronavirus and influenza
US11193184B2 (en) 2019-02-22 2021-12-07 Cda Research Group, Inc. System for use in producing a metal ion suspension and process of using same
EP3939599A3 (fr) * 2007-10-15 2022-03-16 HS Pharmaceuticals, LLC Compositions à base de silicate et procédés de traitement
US12318406B2 (en) 2013-03-15 2025-06-03 Cda Research Group, Inc. Methods of treatment using topical copper ion formulations

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US9107811B2 (en) 2005-06-20 2015-08-18 Sci-Chem International Pty. Ltd. Composition for treating skin lesions
EP3939599A3 (fr) * 2007-10-15 2022-03-16 HS Pharmaceuticals, LLC Compositions à base de silicate et procédés de traitement
AU2014235706B2 (en) * 2013-03-15 2018-11-01 Cda Research Group, Inc. Topical copper ion treatments
US11253544B2 (en) 2013-03-15 2022-02-22 Cda Research Group, Inc. Methods of treatment using topical copper ion formulations
US12318406B2 (en) 2013-03-15 2025-06-03 Cda Research Group, Inc. Methods of treatment using topical copper ion formulations
US10398733B2 (en) 2013-03-15 2019-09-03 Cda Research Group, Inc. Topical copper ion treatments and methods of treatment using topical copper ion treatments in the dermatological areas of the body
US10813948B2 (en) 2013-03-15 2020-10-27 Cda Research Group, Inc. Methods of treatment using topical copper ion formulations
US11000545B2 (en) 2013-03-15 2021-05-11 Cda Research Group, Inc. Copper ion compositions and methods of treatment for conditions caused by coronavirus and influenza
US11007143B2 (en) 2013-03-15 2021-05-18 Cda Research Group, Inc. Topical copper ion treatments and methods of treatment using topical copper ion treatments in the oral-respiratory-otic areas of the body
US11083750B2 (en) 2013-03-15 2021-08-10 Cda Research Group, Inc. Methods of treatment using topical copper ion formulations
WO2014151350A1 (fr) * 2013-03-15 2014-09-25 Cda Research Group, Inc. Traitements topiques par cuivre ionisé et procédés de préparation de traitements topiques par cuivre ionisé utilisés dans des zones anatomiques variées du corps
EP3003247A4 (fr) * 2013-03-15 2017-01-04 CDA Research Group, Inc. Traitements topiques aux ions cuivre
CN105407726A (zh) * 2013-03-15 2016-03-16 Cda研究集团股份有限公司 身体的皮肤病区域中的局部铜离子治疗物
US11298316B2 (en) 2013-03-15 2022-04-12 Cda Research Group, Inc. Topical copper ion treatments and methods of treatment using topical copper ion treatments in the oral-respiratory-otic areas of the body
US11318089B2 (en) 2013-03-15 2022-05-03 Cda Research Group, Inc. Topical copper ion treatments and methods of making topical copper ion treatments for use in various anatomical areas of the body
US12329779B2 (en) 2013-03-15 2025-06-17 Cda Research Group, Inc. Copper ion compositions and methods of treatment for conditions caused by coronavirus and influenza
US11717535B2 (en) 2013-03-15 2023-08-08 Cda Research Group, Inc. Copper ion compositions and methods of treatment for conditions caused by coronavirus and influenza
US11857514B2 (en) 2013-03-15 2024-01-02 Cda Research Group, Inc. Topical copper ion treatments and methods of treatment using topical copper ion treatments in the dermatological areas of the body
US12171867B2 (en) 2013-03-15 2024-12-24 Cda Research Group, Inc. Topical copper ion treatments and methods of making topical copper ion treatments for use in various anatomical areas of the body
US11193184B2 (en) 2019-02-22 2021-12-07 Cda Research Group, Inc. System for use in producing a metal ion suspension and process of using same
US11459638B2 (en) 2019-02-22 2022-10-04 Cda Research Group, Inc. System for use in producing a metal ion suspension and process of using same

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