WO2009066301A2 - Procédés et compositions de traitement de poxvirus au moyen de composés contenant du tellure - Google Patents

Procédés et compositions de traitement de poxvirus au moyen de composés contenant du tellure Download PDF

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Publication number
WO2009066301A2
WO2009066301A2 PCT/IL2008/001538 IL2008001538W WO2009066301A2 WO 2009066301 A2 WO2009066301 A2 WO 2009066301A2 IL 2008001538 W IL2008001538 W IL 2008001538W WO 2009066301 A2 WO2009066301 A2 WO 2009066301A2
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agent
tellurium
virus
pharmaceutical composition
group
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PCT/IL2008/001538
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WO2009066301A3 (fr
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Michael Albeck
Benjamin Sredni
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Biomas Ltd.
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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
    • A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
    • 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
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Definitions

  • Poxviruses are members of the Poxviridae family, which groups viruses associated with diseases that produce poxes in the skin.
  • the prototype of the poxvirus family is the vaccinia virus, which has recently been utilized as a successful vaccine to eradicate smallpox virus.
  • Vaccinia virus is also used as an effective tool for foreign protein expression to elicited strong host immune response.
  • poxviruses are divided two main subfamilies. These include the following:
  • Subfamily Chordopoxvirinae which includes: vaccinia virus (associated with cowpox, vaccinia and smallpox); Orf virus; Fowlpox virus; Sheeppox virus; Myxoma virus; Swinepox virus; Molluscum contagiosum virus; and Yaba monkey tumor virus; and
  • Subfamily Entomopoxvirinae which includes Melolontha entomopoxvirus; Amsacta moorei entomopoxvirus; and Chironomus luridus entomopoxvirus.
  • the smallpox virus is the most notable member of the poxviridea family.
  • the only other poxvirus known to specifically infect humans is the molluscum contagiosum virus (MCV).
  • Molluscum contagiosum is a viral infection, mostly demonstrated in the skin and occasionally in mucosal membranes. MC infects humans, as well as other primates and kangaroos. This poxvirus is common worldwide and accounts for about 1 % of all skin disorders in the United States.
  • MCV-I MCV-2
  • MCV-3 MCV-4
  • MCV-I MCV-2
  • MCV-3 MCV-4
  • MCV-I the most prevalent and MCV-2 seen usually in adults and often sexually transmitted.
  • MC virus primarily affects children (boys more often than girls) and young adults. The incidence of MC infections in young children is around 17 % and peaks between 2-12 years of age.
  • molluscum contagiosum virus there is also a higher incidence of molluscum contagiosum virus in people who are immunocompromised. In HIV-infected people, prevalence is high and rates of 5- 18 % have been reported [Goodman et al., J. Am. Acad. Dermatol. 1987, 17:210-20; Coldiron and Bergstresser, Arch. Dermatol., 1989, 125:357-61; Schwartz and Myskowski, Arch. Dermatol., 1992, Oct;128(10):1407-8].
  • the severity of molluscum contagiosum is inversely related to the CD4 T-lymphocyte count. MC affects any area of the skin but is most common on the body, arms, and legs.
  • molluscum infections are often sexually transmitted and usually affect the genitals, lower abdomen, buttocks, and inner thighs. In rare cases, molluscum infections are also found on the lips, mouth and eyelids.
  • the time from infection to the appearance of lesions typically ranges from 1 week to 6 months, with an average incubation period of 6 weeks. Diagnosis is made on the clinical appearance.
  • Molluscum contagiosum lesions are flesh-colored, dome-shaped, and pearly in appearance.
  • the MC lesions are often 1-5 millimeters in diameter, with a dimpled center.
  • the appearance of MC lesions is generally not associated with pain but is typically associated with itching and sometimes the lesions become irritated. In about
  • the central waxy core of the lesions contains the virus.
  • the virus may spread to neighboring skin areas via autoinoculation.
  • Molluscum lesions may go away on their own in six to nine months, but can persist, via autoinoculation, for up to four years. Molluscum contagiosum is contagious until the bumps are gone, which, if untreated, may be up to 6 months or longer.
  • Medications include, for example, betadine surgical scrub, which is gently scrubbed on the infected area for 5 minutes daily until the lesions resolve.
  • betadine surgical scrub which is gently scrubbed on the infected area for 5 minutes daily until the lesions resolve.
  • the ability of iodine to penetrate intact skin is poor, and hence this methodology is inefficient if performed without a pin prick or needle stick into each molluscum lesion.
  • MC can also be treated by topical application of caustic agents such as cantharidin, silver nitrate, or trichloroacetic acid, treatments that are often painful and not feasible for widespread lesions.
  • MC can be also treated with pharmaceutical modes such as topical podophyllotoxin cream (e.g., Condylox), which is derived from plant resins;
  • Cantharidin (Cantharone, obtained from a blister beetle), applied by the doctor;
  • Imiquimod (Aldara), a topical cream that works by boosting the immune system;
  • Cimentidine (Tagamet), the antiulcer and antiheartburn medication and Cidofovir (Vistide), used for eye infections in people with AIDS - and has been shown to be effective when applied topically to severe MC lesions.
  • Surgical treatments include, for example, cryosurgery, in which liquid nitrogen is used to freeze and destroy lesions, as well as scraping them off with a curette.
  • Pulsed dye laser therapy for molluscum contagiosum is often the current treatment of choice for multiple lesions in a cooperative patient. This therapy is well tolerated, without scars or pigment anomalies. The pulsed dye laser is quick and efficient, but its expense makes it less cost effective than other options. The presently known methods for treating warts therefore suffer major disadvantages, in terms of efficacy, usage convenience, cost-effectiveness and/or adverse side effects associated therewith.
  • tellurium compounds have been described in the art as having immunomodulating properties.
  • a particularly effective family of tellurium-containing compounds is taught, for example, in U.S. Patents Nos. 4,752,614; 4,761,490; 4,764,461 and 4,929,739, whereby another effective family is taught, for example, in PCT International Patent Application No. PCT/IL2005/000989, which are all incorporated by reference as if fully set forth herein.
  • the immunomodulating properties of these tellurium-containing compounds are described, for example, in U.S. Patents Nos. 4,962,207, 5,093,135, 5,102,908, 5,213,899 and in PCT International Patent Application No. PCT/IL2005/000989, which are all incorporated by reference as if fully set forth herein.
  • ammonium trichloro(dioxyethylene-O,O')tellurate which is also referred to herein and in the art as ASlOl .
  • Another promising tellurium-containing compound is [TeO 4 (COCH) 2 J 2 , which is also referred to herein and in the art as SAS.
  • SAS and other ditellurium-containing compounds have been shown to act as effective inhibitors of caspase-1/interleukin-l ⁇ enzyme b (ICE) and their use in various additional therapeutic applications have also been described (see, for example, PCT/IL2005/000989 supra).
  • ASlOl is characterized by low toxicity. Toxicity tests have shown that LD50 values in rats following intravenous and intramuscular administration of ASlOl are 500-1000 folds higher than the immunologically effective dose. Topical application of tellurium-containing compounds has been found effective in the treatment of various skin-related diseases and disorders.
  • HPV human papilloma viruses
  • U.S. Patent No. 6,472,381 discloses the use of ASlOl in petroleum jelly for treating psoriasis.
  • tellurium-containing compounds such as ASlOl are highly effective in the treatment of molluscum contagiosum and other pox viruses.
  • a method of treating a pox virus comprising administering to a subject in need thereof a therapeutically effective amount of a tellurium-containing compound having at least one tellurium dioxo moiety.
  • the administering is effected topically.
  • the administering is effected by applying the therapeutically effective amount of the at least one tellurium-containing compound onto a treated skin or mucosal membrane area.
  • the administering is effected from 4 times daily to once a week.
  • the administering is effected twice daily.
  • the method further comprises administering to the subject an additional active agent.
  • the additional active agent is selected from the group consisting of an antibiotic agent, an antimicrobial agent, an anti- acne agent, an antibacterial agent, an antifungal agent, an antiviral agent, a steroidal antiinflammatory agent, a non-steroidal anti-inflammatory agent, an anesthetic agent, an antipruriginous agent, an antiprotozoal agent, an anti-oxidant, a chemotherapeutic agent, an antidepressant, an anti histamine, a vitamin, a hormone, a keratolytic agent and an antidandruff agent.
  • the method further comprising administering to the subject at least one additional active agent being capable of treating the pox virus.
  • a tellurium-containing compound having at least one tellurium dioxo moiety in the manufacture of a medicament for treating a pox virus.
  • the tellurium-containing compound is utilized in combination with an additional active agent.
  • the additional active agent is selected from the group consisting of an antibiotic agent, an antimicrobial agent, an anti-acne agent, an antibacterial agent, an antifungal agent, an antiviral agent, a steroidal anti-inflammatory agent, a non-steroidal anti-inflammatory agent, an anesthetic agent, an antipruriginous agent, an antiprotozoal agent, an anti-oxidant, a chemotherapeutic agent, an antidepressant, an anti histamine, a vitamin, a hormone, a keratolytic agent and an antidandruff agent.
  • the additional active agent is capable of treating the pox virus.
  • the at least one tellurium- containing compound forms a part of a pharmaceutical composition, the pharmaceutical composition further comprising a pharmaceutically acceptable carrier.
  • a concentration of the at least one tellurium-containing compound ranges from about 0.01 weight percent to about 25 weight percents of the total weight of the composition.
  • a concentration of the at least one tellurium-containing compound ranges from about 5 weight percents to about 25 weight percents of the total weight of the composition.
  • the pharmaceutical composition is formulated for topical application.
  • the pharmaceutical composition is being in a form selected from the group consisting of a cream, an ointment, a paste, a gel, a lotion, a milk, a suspension, a solution, an aerosol, a spray, a foam, a shampoo, a mousse, a serum, a swab, a pledget, a pad, a tincture, a patch and a soap.
  • the pharmaceutical composition further comprises at least one additional active agent.
  • the additional active agent is selected from the group consisting of an antibiotic agent, an antimicrobial agent, an anti-acne agent, an antibacterial agent, an antifungal agent, an antiviral agent, a steroidal anti-inflammatory agent, a non-steroidal anti-inflammatory agent, an anesthetic agent, an antipruriginous agent, an antiprotozoal agent, an anti-oxidant, a chemotherapeutic agent, an antidepressant, an anti histamine, a vitamin, a hormone, a keratolytic agent and an antidandruff agent.
  • the pharmaceutical composition further comprises at least one additional active agent being capable of treating the pox virus.
  • the pharmaceutical composition further comprises at least one ingredient selected from the group consisting of a humectant, a deodorant agent, an antiperspirant, a sun screening agent, a sunless tanning agent, a hair conditioning agent, a pH adjusting agent, a chelating agent, a preservative, an emulsifier, an occlusive agent, an emollient, a thickener, a solubilizing agent, a penetration enhancer, an anti-irritant, a colorant, a propellant and a surfactant.
  • a humectant e.g., a deodorant agent, an antiperspirant, a sun screening agent, a sunless tanning agent, a hair conditioning agent, a pH adjusting agent, a chelating agent, a preservative, an emulsifier, an occlusive agent, an emollient, a thickener, a solubilizing agent, a penetration enhancer, an anti
  • the pharmaceutical composition has a pH that ranges from 4 to 8.
  • a pharmaceutical composition packaged in a packaging material and identified in print, in or on the packaging material, for use in the treatment of a pox virus comprising a tellurium-containing compound having at least one tellurium dioxo moiety and a pharmaceutically acceptable carrier.
  • a concentration of the at least one tellurium-containing compound ranges from about 0.01 weight percent to about 25 weight percents of the total weight of the composition.
  • a concentration of the at least one tellurium-containing compound ranges from about 5 weight percents to about 25 weight percents of the total weight of the composition.
  • the pharmaceutical composition is formulated for topical application.
  • the pharmaceutical composition is in a form selected from the group consisting of a cream, an ointment, a paste, a gel, a lotion, a milk, a suspension, a solution, an aerosol, a spray, a foam, a shampoo, a mousse, a serum, a swab, a pledget, a pad, a tincture, a patch and a soap.
  • the pharmaceutical composition further comprises at least one additional active agent.
  • the additional active agent is selected from the group consisting of an antibiotic agent, an antimicrobial agent, an anti-acne agent, an antibacterial agent, an antifungal agent, an antiviral agent, a steroidal anti-inflammatory agent, a non-steroidal anti-inflammatory agent, an anesthetic agent, an antipruriginous agent, an antiprotozoal agent, an anti-oxidant, a chemotherapeutic agent, an antidepressant, an anti histamine, a vitamin, a hormone, a keratolytic agent and an antidandruff agent.
  • the pharmaceutical composition further comprises at least one additional active agent being capable of treating the pox virus.
  • the pharmaceutical composition further comprising at least one ingredient selected from the group consisting of a humectant, a deodorant agent, an antiperspirant, a sun screening agent, a sunless tanning agent, a hair conditioning agent, a pH adjusting agent, a chelating agent, a preservative, an emulsifier, an occlusive agent, an emollient, a thickener, a solubilizing agent, a penetration enhancer, an anti-irritant, a colorant, a propellant and a surfactant.
  • a humectant e.g., a deodorant agent, an antiperspirant, a sun screening agent, a sunless tanning agent, a hair conditioning agent, a pH adjusting agent, a chelating agent, a preservative, an emulsifier, an occlusive agent, an emollient, a thickener, a solubilizing agent, a penetration enhancer, an anti
  • the pharmaceutical composition has a pH that ranges from 4 to 8.
  • the pox virus is selected from the group consisting of vaccinia virus, Orf virus, Fowlpox virus, Sheeppox virus, Myxoma virus, Swinepox virus, Molluscum contagiosum virus, Yaba monkey tumor virus, Melolontha entomopoxvirus, Amsacta moorei entomopoxvirus, and Chironomus luridus entomopoxvirus.
  • the pox virus is Molluscum contagiosum virus.
  • the tellurium-containing compound is selected from the group consisting of tellurium dioxide (TeO 2 ), a complex OfTeO 2 , a compound having general Formula I:
  • Y is selected from the group consisting of ammonium, phosphonium, potassium, sodium and lithium;
  • X is a halogen atom; and each Of R 1 -R 22 is independently selected from the group consisting of hydrogen, hydroxyalkyl, hydroxy, thiohydroxy, alkyl, alkenyl, alkynyl, alkoxy, thioalkoxy, halogen, haloalkyl, carboxy, carbonyl, alkylcarbonylalkyl, carboxyalkyl, acyl, amido, cyano, N-monoalkylamidoalkyl, N,N-dialkylamidoalkyl, cyanoalkyl, alkoxyalkyl, carbamyl, cycloalkyl, heteroalicyclic, sulfonyl, sulfinyl, sulfate, amine, aryl, heteroaryl, phosphate, phosphonate and sulfoneamido.
  • the tellurium-containing compound has general Formula I. According to some embodiments of the invention, t, u and v are each 0.
  • Rj, R 8 , R 9 and Ri 0 are each hydrogen.
  • X is chloro
  • Y is ammonium.
  • the tellurium-containing compound is ammonium trichloro(dioxyethylene-O,O')tellurate.
  • the pox virus is molluscum contagiosum virus and the tellurium-containing compound is ammonium trichloro(dioxyethylene-O,O')tellurate.
  • the method comprising administering to a subject in need thereof a therapeutically effective amount of ammonium trichloro(dioxyethylene-O,O')tellurate.
  • the method further comprises administering to the subject at least one additional active agent being capable of treating molluscum contagiosum virus.
  • at least one additional active agent being capable of treating molluscum contagiosum virus.
  • ammonium trichloro(dioxyethylene-O,O')tellurate in the manufacture of a medicament for treating molluscum contagiosum virus.
  • the ammonium trichloro(dioxyethylene-O,O')tellurate is utilized in combination with an additional active agent that is capable of treating molluscum contagiosum virus.
  • compositions packaged in a packaging material and identified in print, in or on the packaging material, for use in the treatment of molluscum contagiosum virus comprising ammonium trichloro(dioxyethylene-
  • method refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts.
  • treating includes abrogating, substantially inhibiting, slowing or reversing the progression of a condition, substantially ameliorating clinical or aesthetical symptoms of a condition or substantially preventing the appearance of clinical or aesthetical symptoms of a condition.
  • composition or method may include additional ingredients and/or steps, but only if the additional ingredients and/or steps do not materially alter the basic and novel characteristics of the claimed composition or method.
  • the term "pharmaceutically acceptable” means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, and more particularly in humans.
  • physiologically suitable carrier and “pharmaceutically acceptable carrier” are interchangeably used and refer to an approved carrier or a diluent that does not cause significant irritation to an organism and does not abrogate the biological activity and properties of the administered conjugate.
  • the singular form “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise.
  • the term “a compound” or “at least one compound” may include a plurality of compounds, including mixtures thereof.
  • FIGs. IA-C present photographs of an afflicted area of a female patient diagnosed with molluscum contagiosum (MC), before treatment ( Figure IA) and following 2 weeks (Figure IB) and 14 weeks (Figure 1C) treatment with topically applied ASlOl 20 % cream (20 % w/v ASlOl in 5 % DMSO in Vaseline cream), demonstrating the complete clearance of MC lesions without leaving any scars; and
  • FIGs. 2A-C present photographs of an afflicted area of a female patient diagnosed with molluscum contagiosum (MC), before treatment ( Figure IA) and following 2 weeks (Figure IB) and 4 weeks (Figure 1C) treatment with topically applied
  • the present invention is of tellurium-containing compounds which can be beneficially used in the treatment of various pox viruses.
  • the present embodiments are of compositions containing, and methods utilizing, tellurium- containing compounds having one or more tellurium dioxo moiety for treating pox viruses such as molluscum contagiosum.
  • the principles and operation of the methods, compositions and uses according to the present embodiments may be better understood with reference to the drawings and accompanying descriptions.
  • tellurium-containing compounds have been described in the art as immunomodulators.
  • a particularly effective family of tellurium-containing compounds is described, for example, in U.S. Patents Nos. 4,752,614; 4,761,490; 4,764,461 and 4,929,739.
  • the immunomodulating properties of this family of tellurium-containing compounds is described, for example, in U.S. Patents Nos. 4,962,207, 5,093,135, 5,102,908 and 5,213,899, which are all incorporated by reference as if fully set forth herein.
  • ammonium trichloro(dioxyethylene-O,O')tellurate which is also referred to herein and in the art as ASlOl.
  • LD50 values in rats following intravenous and intramuscular dosage of ASlOl are 500-1000 folds higher than the immunology effective dose.
  • These tellurium-containing compounds are therefore further characterized as substantially non-toxic, rendering them highly suitable as therapeutic agents.
  • tellurium-containing compounds could serve as potent therapeutic agents against infections caused by pox viruses, while being devoid of the disadvantages associated with the presently known technologies for treating pox viruses described hereinabove.
  • a tellurium-containing compound such as ASlOl was highly efficient, resulting in high treatment responsiveness and minimized side effects.
  • a method of treating a pox virus is effected by administering to a subject in need thereof a therapeutically effective amount of a tellurium-containing compound as described herein.
  • tellurium-containing compound as described herein, in the manufacture of a medicament for treating a pox virus.
  • tellurium-containing compound encompasses any compound that includes one or more tellurium atoms.
  • the tellurium-containing compound may be an inorganic compound or an organic compound.
  • Inorganic tellurium-containing compounds include, for example, tellurium dioxide (TeO 2 ) per se.
  • Organic tellurium-containing compounds may be in the form of an organic complex such as, for example, a TeO 2 complex with citric acid or ethylene glycol, which may form TeO 2 as an end product in aqueous solutions.
  • a representative example of the latter is the complex TeO 2 HOCH 2 CH 2 OHNH 4 Cl.
  • the tellurium-containing compounds described herein include one or more tellurium atoms and one or more organic moieties that are attached thereto, for example, ammonium salts, or any other salts, of halogenated tellurium-containing compounds having a bidentate cyclic moiety attached to the tellurium atom.
  • the bidentate cyclic moiety is preferably a di-oxo moiety having two oxygen atoms attached to the tellurium atom.
  • the bidentate cyclic moiety can optionally be a di-thio moiety, in which two sulfur atoms are attached to the tellurium atom.
  • Preferred compounds in this category are collectively represented by the general Formula I:
  • each of t, u and v is independently 0 or 1, such that the compound may include a five-membered ring, a six-membered ring, or a seven- membered ring.
  • each of t, u and v is 0, such that the compound includes a five-membered ring.
  • X is a halogen atom, as described hereinabove, and is preferably chloro.
  • Y is selected from the group consisting of ammonium, phsophonium, potassium, sodium and lithium, and is preferably ammonium.
  • Each Of R 1 -R 10 is independently selected from the group consisting of hydrogen, hydroxyalkyl, hydroxy, thiohydroxy, alkyl, alkenyl, alkynyl, alkoxy, thioalkoxy, halogen, haloalkyl, carboxy, carbonyl, alkylcarbonylalkyl, alkoxy, carboxyalkyl, acyl, amido, cyano, N-monoalkylamidoalkyl, N,N-dialkylamidoalkyl, cyanoalkyl, alkoxyalkyl, carbamyl, cycloalkyl, heteroalicyclic, sulfonyl, sulfinyl, sulfate, amine, aryl, heteroaryl, phosphate, phosphonate and sulfoneamido.
  • alkyl refers to a saturated aliphatic hydrocarbon including straight chain and branched chain groups.
  • the alkyl group has 1 to 20 carbon atoms. More preferably, the alkyl is a medium size alkyl having 1 to 10 carbon atoms. Most preferably, unless otherwise indicated, the alkyl is a lower alkyl having 1 to 5 carbon atoms.
  • the alkyl group may be substituted or unsubstituted. When substituted, the substituent group can be as described herein for Ri.
  • hydroxyalkyl refers to an alkyl, as this term is defined herein, substituted by a hydroxy group, as defined herein, and includes, for example, hydroxymethyl, hydroxyethyl, hydroxypropyl and hydroxy-n-butyl.
  • halogen which is also referred to herein interchangeably as “a halogen atom” or “halo”, includes chloro (Cl), bromo (Br), iodo (I) and fluoro (F).
  • haloalkyl refers to an alkyl, as this term is defined herein, substituted by a halogen, as defined herein, and includes, for example, chloromethyl, 2-iodoethyl, 4- bromo-n-butyl, iodoethyl, 4-bromo-n-pentyl and the like.
  • alkyl as this term is defined herein, substituted by a halogen, as defined herein, and includes, for example, chloromethyl, 2-iodoethyl, 4- bromo-n-butyl, iodoethyl, 4-bromo-n-pentyl and the like.
  • alkanoyloxy refers to a carbonyl group, as define herein and includes, for example, acetyl, propionyl, butanoyl and the like.
  • carboxyalkyl refers to an alkyl, as this term is defined herein, substituted by a carboxy group, as defined herein, and includes, for example, carboxymethyl, carboxyethyl, ethylenecarboxy and the like.
  • alkylcarbonylalkyl refers to an alkyl, as this term is defined herein, substituted by a carbonyl group, as defined herein, and includes, for example, methanoylmethyl, ethanoylethyl and the like.
  • amidoalkyl refers to an alkyl, as this term is defined herein, substituted by an amide group, as defined herein, and includes, for example, -CH 2 CONH 2 ; - CH 2 CH 2 CONH 2 ; -CH 2 CH 2 CH 2 CONH 2 and the like.
  • cyanoalkyl refers to an alkyl, as this term is defined herein, substituted by an cyano group, as defined herein, and includes, for example, -CH 2 CN; -CH 2 CH 2 CN; - CH 2 CH 2 CH 2 CN and the like.
  • N-monoalkylamidoalkyl refers to an alkyl, as this term is defined herein, substituted by an amide group, as defined herein, in which one of R' and R" is an alkyl, and includes, for example, -CH 2 CH 2 CONHCH 3 , and -CH- 2 CONHCH 2 CH 3 .
  • N,N-dialkylamidoalkyl refers to an alkyl, as this term is defined herein, substituted by an amide group, as defined herein, in which both R 1 and R" are alkyl, and includes, for example, -CH 2 CON(CH 3 ) 2 ; CH 2 CH 2 CON(CH 2 -CH 3 ) 2 and the like.
  • a "cycloalkyl” group refers to an all-carbon monocyclic or fused ring (i.e., rings which share an adjacent pair of carbon atoms) group wherein one of more of the rings does not have a completely conjugated pi-electron system.
  • cycloalkyl groups examples, without limitation, are cyclopropane, cyclobutane, cyclopentane, cyclopentene, cyclohexane, cyclohexadiene, cycloheptane, cycloheptatriene, and adamantane.
  • a cycloalkyl group may be substituted or unsubstituted. When substituted, the substituent group can be as described herein for Rl.
  • An "alkenyl” group refers to an alkyl group which consists of at least two carbon atoms and at least one carbon-carbon double bond.
  • alkynyl refers to an alkyl group which consists of at least two carbon atoms and at least one carbon-carbon triple bond.
  • aryl group refers to an all-carbon monocyclic or fused-ring polycyclic (i.e., rings which share adjacent pairs of carbon atoms) groups having a completely conjugated pi-electron system. Examples, without limitation, of aryl groups are phenyl, naphthalenyl and anthracenyl. The aryl group may be substituted or unsubstituted.
  • the substituent group can be as described herein for Rl .
  • heteroaryl group refers to a monocyclic or fused ring (i.e., rings which share an adjacent pair of atoms) group having in the ring(s) one or more atoms, such as, for example, nitrogen, oxygen and sulfur and, in addition, having a completely conjugated pi-electron system.
  • heteroaryl groups include pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrimidine, quinoline, isoquinoline and purine.
  • the heteroaryl group may be substituted or unsubstituted. When substituted, the substituent group can be as described herein for Rl .
  • a “heteroalicyclic” group refers to a monocyclic or fused ring group having in the ring(s) one or more atoms such as nitrogen, oxygen and sulfur.
  • the rings may also have one or more double bonds. However, the rings do not have a completely conjugated pi-electron system.
  • the heteroalicyclic may be substituted or unsubstituted. When substituted, the substituent group can be as described herein for Rl.
  • a "hydroxy" group refers to an -OH group.
  • alkoxy refers to both an -O-alkyl and an -O-cycloalkyl group, as defined herein.
  • aryloxy refers to both an -O-aryl and an -O-heteroaryl group, as defined herein.
  • a “thiohydroxy” group refers to a -SH group.
  • a “thioalkoxy” group refers to both an -S-alkyl group, and an -S-cycloalkyl group, as defined herein.
  • a “thioaryloxy” group refers to both an -S-aryl and an -S-heteroaryl group, as defined herein.
  • a “sulfonamido” group refers to a -S(O) 2 -NR' R" group or a R' S(O) 2 -NR", with R' is as defined herein and R" is as defined for R.
  • a “carbamyl” or “carbamate” group refers to an -OC(O)-NR 5 R" group or a R" OC(O)-NR'- group, where R' and R" are as defined herein.
  • amino refers to an -NR'R" group where R' and R" are as defined herein.
  • An “amido” group refers to a -C(O)-NR 5 R" group or a R 5 C(O)-NR" group, where R' and R" are as defined herein.
  • a "nitro” group refers to an -NO 2 group.
  • a “cyano” group refers to a -C ⁇ N group.
  • phosphonyl describes a -0-P(O)(OR' )(0R") group, with R' and R" as defined hereinabove.
  • phosphinyl describes a -PR' R" group, with R 5 and R" as defined hereinabove.
  • the compounds in this category are salts of organic tellurium-containing compounds.
  • the salts can be, for example, ammonium salts, phsophonium salts and alkaline salts such as potassium salts, sodium salts, lithium salts and the like.
  • Y in Formula I above can be a phosphonium group, as defined herein, an ammonium group, as defined herein, potassium (K + ), sodium (Na + ) or lithium (Li + ).
  • phosphonium describes a -P + R 1 R 11 R'" group, with R' and R" as defined herein and R'" is as defined for R'.
  • phsophonium as used herein, further refers to a -P + R 6 group, wherein each of the six R substituents is independently as defined herein for R, R" and R"'.
  • ammonium describes a -N + R 1 R 11 R" group, with R 1 , R" and R" as defined herein.
  • More preferred compounds in this category include compounds having the general Formula I described above, in which Y is ammonium or phosphonium, t, u and v are each 0, and each of Ri, R 8 , R 9 and R 10 is independently hydrogen or alkyl. These compounds can be represented by the following structure:
  • each of R 1 , R 8 , R 9 and Ri 0 is independently hydrogen or alkyl, whereas a preferred alkyl is methyl, and X is halogen, preferably chloro.
  • This compound is ammonium trichloro(dioxyethylene-O,O')tellurate, which is also referred to herein and in the art as ASlOl.
  • ASlOl can be readily prepared by reacting tetrahalotelluride such as TeCl 4 with a dihydroxy compound, as is described in detail in U.S. Patents Nos. 4,752,614, 4,761,490, 4,764,461 and 4,929,739, which are incorporated by reference as if fully set forth herein.
  • organic tellurium-containing compound that are suitable for use in the context of the present embodiments include halogenated tellurium having a bidentate cyclic moiety attached to the tellurium atom.
  • the bidentate cyclic moiety is preferably a di-oxo ligand having two oxygen atoms attached to the tellurium atom.
  • the bidentate cyclic moiety can be a di-thio ligand, in which two sulfur atoms are attached to the tellurium atom.
  • t, u, v, X and Ri-R 10 are as defined hereinabove. More preferred compounds are those in which t, u, and v are each 0, and X is chloro, such as, but not limited to, the compound having the following structure:
  • the above compound is also known and referred to herein as AS 103.
  • organic tellurium-containing compounds having Formulae I and II can be readily prepared by reacting tetrahalotelluride such as TeCl 4 with a dihydroxy compound, as is described in detail in U.S. Patents Nos. 4,752,614, 4,761,490, 4,764,461 and 4,929,739, which are incorporated by reference as if fully set forth herein.
  • organic tellurium-containing compounds that are suitable for use in the context of the present embodiments include compounds in which two bidentatic cyclic moieties are attached to the tellurium atom.
  • each of the cyclic moieties is a di-oxo moiety.
  • one or more of the cyclic moieties is a di-thio moiety.
  • each of j and k is independently an integer from 0 to 4, such that the compound may include a five-membered ring, a six- membered ring, a seven-membered ring, an eight-membered ring and/or a nine- membered ring.
  • each of j and k is an integer from 0 to 2, such that the compound includes a five-membered ring, a six-membered ring and/or a seven- membered ring. More preferably, each of j and k is 0.
  • R 1 -Ri 2 are as defined hereinabove for R 1 -RiO.
  • More preferred compounds in this category are those in which j and k are each 0, and R 3 , R 4 , Rg and Ri 0 are each hydrogen, having the following structure:
  • each of Rn-Ri 4 is independently selected from the group consisting of hydrogen, hydroxyalkyl, hydroxy, thiohydroxy, alkyl, alkenyl, alkynyl, alkoxy, thioalkoxy, halogen, haloalkyl, carboxy, carbonyl, alkylcarbonylalkyl, alkoxy, carboxyalkyl, acyl, amido, cyano, N-monoalkylamidoalkyl, N,N-dialkylamidoalkyl, cyanoalkyl, alkoxyalkyl, carbamyl, cycloalkyl, heteroalicyclic, sulfonyl, sulfinyl, sulfate, amine, aryl, heteroaryl, phosphate, phosphonate and sulfoneamido, as these terms are defined herein.
  • the most preferred compound in this category is a compound in which each of R ⁇ i-Ri4 is hydrogen. This compound is also known as AS 102.
  • each Of R 15 -R 22 is independently selected from the group consisting of hydrogen, hydroxyalkyl, hydroxy, thiohydroxy, alkyl, alkenyl, alkynyl, alkoxy, thioalkoxy, halogen, haloalkyl, carboxy, carbonyl, alkylcarbonylalkyl, alkoxy, carboxyalkyl, acyl, amido, cyano, N-monoalkylamidoalkyl, N,N-dialkylamidoalkyl, cyanoalkyl, alkoxyalkyl, carbamyl, cycloalkyl, heteroalicyclic, sulfonyl, sulfinyl, sulfate, amine, aryl, heteroaryl, phosphate, phosphonate and sulfoneamido, as these terms are defined herein; and m and n are each an integer from O to 3.
  • Preferred compounds in this category are those in which m and n are each O.
  • the presently most preferred compound in this family is a compound in which Ri5, Ri8, Ri9 and R 22 are all hydrogen, referred to hereinafter as SAS, and which has the following structure:
  • the tellurium-containing compound is of Formula I, most preferably, in which Y is ammonium, t, u and v are each 0, and each of R 1 , R 8 , R 9 and R 10 is independently methyl and X is chloro, also known as AS 101.
  • ASlOl a representative example of a tellurium-containing compound according to the present embodiments, was found to be highly efficient in treating MC.
  • the treatment was accompanied with minimal or no adverse side effects and the ailments (e.g., lesions) were substantially completely removed.
  • the high efficiency of the treatment according to the present embodiments is attributed, at least in part, to the immunomodulating and anti-viral activity of the tellurium-containing compounds described herein.
  • treatment with the tellurium-containing compounds described herein affects not only the manifested visible lesions but rather suppress the cause of the ailment - the virus itself.
  • viral particles that may be lurking in normal-appearing areas surrounding the lesions are also destroyed.
  • the method according to this aspect of the present invention can therefore be efficiently utilized for treating a pox virus.
  • treating a pox virus also encompasses treating any manifestation of a pox virus, typically including skin and/or mucosal ailments caused by a pox virus.
  • a skin and/or mucosal membrane ailment caused by a pox virus which also referred to herein interchangeably as “pox virus-caused ailment”, encompasses any ailment that is associated, either directly or indirectly, with any type of a virus of the poxviridae family described hereinabove.
  • Exemplary poxviruses that are treatable by the tellurium-containing compounds described herein, according to the present embodiments, include those of the subfamily chordopoxvirinae, which includes, for example, the type species vaccinia virus (associated with cowpox, vaccinia and smallpox); Orf virus; Fowlpox virus; Sheeppox virus; Myxoma virus; Swinepox virus; Molluscum contagiosum virus; and Yaba monkey tumor virus; and those of the subfamily Entomopoxvirinae, which includes the type species Melolontha entomopoxvirus; Amsacta moorei entomopoxvirus; and
  • Chironomus luridus entomopoxvirus Chironomus luridus entomopoxvirus.
  • the methods and uses described herein are for treating molluscum contagiosum (MC) virus, including skin and mucosal infections caused thereby.
  • MC molluscum contagiosum
  • pox viruses typically manifested in various skin areas and mucosal membranes, including, for example, body, arms, legs, and genital areas, as well as the lower abdomen, buttocks, and inner thighs. In rare cases, molluscum infections are also found on the lips, mouth and eyelids.
  • Subjects afflicted with a pox virus are preferably humans, but can also be other mammals such as, for example, primates and kangaroos.
  • the compounds described above can be administered to a subject afflicted by a pox virus-caused ailment by any of various systemic routes.
  • Suitable routes of systemic administration may, for example, include the inhalation, oral, buccal, rectal, transmucosal, transdermal, intradermal, transnasal, intestinal and/or parenteral routes; the intramuscular, subcutaneous and/or intramedullary injection routes; the intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal, and/or intraocular injection routes; and/or the route of direct injection into a tissue region of a subject of the present embodiments.
  • a therapeutically effective amount of the tellurium-containing compounds described herein may range, for example, from about 0.01 mg/m /day to about 10.0 mg/m /day and thus can be for example, 0.01 mg/m /day, 0.02 mg/m 2 /day, 0.03 mg/m 2 /day, 0.04 mg/m 2 /day, 0.05 mg/m 2 /day, 0.06 mg/m 2 /day, 0.07 mg/m 2 /day, 0.08 mg/m 2 /day, 0.09 mg/m 2 /day and 0.1 mg/m 2 /day.
  • the therapeutically effective amount when administered parenterally, is 0.1 mg/m 2 /day and higher and thus can be, for example, 0.2 mg/m 2 /day, 0.3 mg/m 2 /day, 0.4 mg/m 2 /day, 0.5 mg/m 2 /day, 0.6 mg/m 2 /day, 0.7 mg/m 2 /day, 0.8 mg/m 2 /day, 0.9 mg/m 2 /day, 1.0 mg/m 2 /day, 2.0 mg/m 2 /day, 3.0 mg/m 2 /day, 4.0 mg/m 2 /day, 5.0 mg/m 2 /day, and up to 10.0 mg/m 2 /day.
  • a daily dose typically ranges between 1 mg and 100 mg.
  • the compounds described above can be administered to a subject afflicted by a pox virus by local routes, and more preferably, the compounds are administered topically.
  • Topical application of the tellurium-containing compounds described herein is preferably effected by applying onto a treated skin or mucosal membrane area a therapeutically effective amount the compound.
  • the phrase "treated area” encompasses the affected area (e.g., the lesion(s)) as well as the tissues surrounding the indicated area.
  • the topical application is effected on and around the clinical manifestation (e.g., lesion(s)).
  • Treatment regime can range from 4 times daily to once a week, depending on the severity of the ailment.
  • regime includes application of from twice daily to once every other day and more preferably, it includes one or two daily administrations.
  • the tellurium-containing compounds described herein can be utilized in combination with an additional active agent.
  • the method described herein can further comprise, in addition to administering the tellurium-containing compounds described above, co-administration of an additional active agent.
  • the co-administration can be effected prior to, concomitant with or subsequent to the administration of the tellurium-containing compound.
  • the additional active agent is typically used for providing an additive beneficial effect in terms of the ailment being treated, conditions associated with the ailment being treated or other parameters such as psychological effects and prophylactic effects.
  • exemplary additional active agents include, without limitation, one or more, or any combination of an antibiotic agent, an antimicrobial agent, an anti-acne agent, an antibacterial agent, an antifungal agent, an antiviral agent, a steroidal anti-inflammatory agent, a non-steroidal anti-inflammatory agent, an anesthetic agent, an antipruriginous agent, an antiprotozoal agent, an anti-oxidant, a chemotherapeutic agent, an antidepressant, an anti histamine, a vitamin, a hormone and an anti-dandruff agent.
  • an antibiotic agent an antimicrobial agent, an anti-acne agent, an antibacterial agent, an antifungal agent, an antiviral agent, a steroidal anti-inflammatory agent, a non-steroidal anti-inflammatory agent, an anesthetic agent, an antipruriginous agent, an antiprotozoal agent, an anti-oxidant, a chemotherapeutic agent, an antidepressant, an anti histamine, a vitamin,
  • Suitable anti-acne agents for use in this context of the present embodiments include, without limitation, keratoly es such as salicylic acid, sulfur, glycolic, pyruvic acid, resorcinol, and N-acetylcysteine and retinoids such as retinoic acid and its derivatives (e.g., cis and trans, esters).
  • keratoly es such as salicylic acid, sulfur, glycolic, pyruvic acid, resorcinol, and N-acetylcysteine
  • retinoids such as retinoic acid and its derivatives (e.g., cis and trans, esters).
  • Suitable antibiotics for use in this context of the present embodiments include, without limitation, benzoyl peroxide, octopirox, erythromycin, zinc, tetracyclin, triclosan, azelaic acid and its derivatives, phenoxy ethanol and phenoxy proponol, ethylacetate, clindamycin and meclocycline; sebostats such as flavinoids; alpha and beta hydroxy acids; and bile salts such as scymnol sulfate and its derivatives, deoxycholate and cholate.
  • non-steroidal anti-inflammatory agents include, without limitation, oxicams, such as piroxicam, isoxicam, tenoxicam, sudoxicam, and CP- 14,304; salicylates, such as aspirin, disalcid, benorylate, trilisate, safapryn, solprin, diflunisal, and fendosal; acetic acid derivatives, such as diclofenac, fenclofenac, indomethacin, sulindac, tolmetin, isoxepac, furofenac, tiopinac, zidometacin, acematacin, fentiazac, zomepirac, clindanac, oxepinac, felbinac, and ketorolac; fenamates, such as mefenamic, meclofenamic, flufenamic, niflumic, and
  • non-steroidal anti-inflammatory agents may also be employed, as well as the dermatologically acceptable salts and esters of these agents.
  • etofenamate a flufenamic acid derivative
  • steroidal anti-inflammatory drugs include, without limitation, corticosteroids such as hydrocortisone, hydroxyltriamcinolone, alpha-methyl dexamethasone, dexamethasone-phosphate, beclomethasone dipropionates, clobetasol valerate, desonide, desoxymethasone, desoxycorticosterone acetate, dexamethasone, dichlorisone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, fluclorolone acetonide, fludrocortisone, flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortine butylesters, fluocortolone, fluprednidene (fluprednylidene) acetate, flurandrenolone, halcinonide, hydrocortisone acetate, hydrocortisone butyrate,
  • Suitable antipruritic agents include, without limitation, pharmaceutically acceptable salts of methdilazine and trimeprazine.
  • anesthetic drugs that are suitable for use in context of the present embodiments include pharmaceutically acceptable salts of lidocaine, bupivacaine, chlorprocaine, dibucaine, etidocaine, mepivacaine, tetracaine, dyclonine, hexylcaine, procaine, cocaine, ketamine, pramoxine and phenol.
  • Suitable antimicrobial agents including antibacterial, antifungal, antiprotozoal and antiviral agents, for use in context of the present embodiments include, without limitation, beta-lactam drugs, quinolone drugs, ciprofloxacin, norfloxacin, tetracycline, erythromycin, amikacin, triclosan, doxycycline, capreomycin, chlorhexidine, chlortetracycline, oxytetracycline, clindamycin, ethambutol, metronidazole, pentamidine, gentamicin, kanamycin, lineomycin, methacycline, methenamine, minocycline, neomycin, netilmicin, streptomycin, tobramycin, and miconazole.
  • tetracycline hydrochloride farnesol, erythromycin estolate, erythromycin stearate (salt), amikacin sulfate, doxycycline hydrochloride, chlorhexidine gluconate, chlorhexidine hydrochloride, chlortetracycline hydrochloride, oxytetracycline hydrochloride, clindamycin hydrochloride, ethambutol hydrochloride, metronidazole hydrochloride, pentamidine hydrochloride, gentamicin sulfate, kanamycin sulfate, lineomycin hydrochloride, methacycline hydrochloride, methenamine hippurate, methenamine mandelate, minocycline hydrochloride, neomycin sulfate, netilmicin sulfate, paromomycin sulfate, streptomycin sulfate, tobramycin sulfate, mic
  • Non-limiting examples of anti-oxidants that are usable in the context of the present embodiments include ascorbic acid (vitamin C) and its salts, ascorbyl esters of fatty acids, ascorbic acid derivatives (e.g., magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbyl sorbate), tocopherol (vitamin E), tocopherol sorbate, tocopherol acetate, other esters of tocopherol, butylated hydroxy benzoic acids and their salts, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (commercially available under the trade name Trolox R ), gallic acid and its alkyl esters, especially propyl gallate, uric acid and its salts and alkyl esters, sorbic acid and its salts, lipoic acid, amines (e.g., N,N-diethylhydroxylamine, amino-guanidine), sulfhydryl compounds (e.
  • Non-limiting examples of chemotherapeutic agents usable in context of the present embodiments include daunorubicin, doxorubicin, idarubicin, amrubicin, pirarubicin, epirubicin, mitoxantrone, etoposide, teniposide, vinblastine, vincristine, mitomycin C, 5-FU, paclitaxel, docetaxel, actinomycin D, colchicine, topotecan, irinotecan, gemcitabine cyclosporin, verapamil, valspodor, probenecid, MK571, GF 120918, LY335979, biricodar, terfenadine, quinidine, pervilleine A and XR9576.
  • Non-limiting examples of antidepressants usable in context of the present embodiments include norepinephrine-reuptake inhibitors ("NRIs"), selective-serotonin- reuptake inhibitors (SSRIs), monoamine-oxidase inhibitors (MAOIs), serotonin-and- noradrenaline-reuptake inhibitors ("SNFIs), corticotropin-releasing factor (CRF) antagonists, ⁇ -adrenoreceptor antagonists, NKl -receptor antagonists, 5-HTiA-receptor agonist, antagonists, and partial agonists and atypical antidepressants, as well as norepinephrine-reuptake inhibitors such as, but are not limited to amitriptyline, desmethylamitriptyline, clomipramine, doxepin, imipramine, imipramine-oxide, trimipramine; adinazolam, amiltriptylinoxide, amoxapine, desipra
  • Exemplary anti-dandruff ingredients usable in context of the present embodiments include, without limitation, zinc pyrithione, shale oil and derivatives thereof such as sulfonated shale oil, selenium sulfide, sulfur; salicylic acid, coal tar, povidone-iodine, imidazoles such as ketoconazole, dichlorophenyl imidazolodioxalan, clotrimazole, itraconazole, miconazole, climbazole, tioconazole, sulconazole, butoconazole, fluconazole, miconazolenitrite and any possible stereo isomers and derivatives thereof such as anthralin, piroctone olamine (Octopirox), selenium sulfide, and ciclopirox olamine, and mixtures thereof.
  • zinc pyrithione shale oil and derivatives thereof such as sulfonated shale oil, seleni
  • Non-limiting examples of vitamins usable in context of the present embodiments include vitamin A and its analogs and derivatives: retinol, retinal, retinyl palmitate, retinoic acid, tretinoin, iso-tretinoin (known collectively as retinoids), vitamin E (tocopherol and its derivatives), vitamin C (L-ascorbic acid and its esters and other derivatives), vitamin B 3 (niacinamide and its derivatives), alpha hydroxy acids (such as glycolic acid, lactic acid, tartaric acid, malic acid, citric acid, etc.) and beta hydroxy acids (such as salicylic acid and the like).
  • vitamin A and its analogs and derivatives include vitamin A and its analogs and derivatives: retinol, retinal, retinyl palmitate, retinoic acid, tretinoin, iso-tretinoin (known collectively as retinoids), vitamin E (tocopherol and its derivatives), vitamin C (L-ascorbic
  • Non-limiting examples of dermatological active ingredients usable in context of the present embodiments include jojoba oil and aromatic oils such as methyl salicylate, wintergreen, peppermint oil, bay oil, eucalyptus oil and citrus oils, as well as ammonium phenolsulfonate, bismuth subgallate, zinc phenolsulfonate and zinc salicylate.
  • Non-limiting examples of antifungal agents include miconazole, clotrimazole, butoconazole, fenticonasole, tioconazole, terconazole, sulconazole, fluconazole, haloprogin, ketonazole, ketoconazole, oxinazole, econazole, itraconazole, terbinafine, nystatin and griseofulvin.
  • Non-limiting examples of antihistamines usable in context of the present embodiments include chlorpheniramine, brompheniramine, dexchlorpheniramine, tripolidine, clemastine, diphenhydramine, promethazine, piperazines, piperidines, astemizole, loratadine and terfenadine.
  • Suitable hormones for use in the context of the present embodiments include, for example, androgenic compounds and progestin compounds.
  • Representative examples of androgenic compounds include, without limitation, methyltestosterone, androsterone, androsterone acetate, androsterone propionate, androsterone benzoate, androsteronediol, androsteronediol-3-acetate, androsteronediol- 17-acetate, androsteronediol 3-17-diacetate, androsteronediol- 17-benzoate, androsteronedione, androstenedione, androstenediol, dehydroepiandrosterone, sodium dehydroepiandrosterone sulfate, dromostanolone, dromostanolone propionate, ethylestrenol, fluoxymesterone, nandrolone phenpropionate, nandrolone decanoate, nandrolone furylpropionate, nandrolone cyclohexane-propionate, nandrol
  • progestin compounds include, without limitation, desogestrel, dydrogesterone, ethynodiol diacetate, medroxyprogesterone, levonorgestrel, medroxyprogesterone acetate, hydroxyprogesterone caproate, norethindrone, norethindrone acetate, norethynodrel, allylestrenol, 19-nortestosterone, lynoestrenol, quingestanol acetate, medrogestone, norgestrienone, dimethisterone, ethisterone, cyproterone acetate, chlormadinone acetate, megestrol acetate, norgestimate, norgestrel, desogrestrel, trimegestone, gestodene, nomegestrol acetate, progesterone, 5 ⁇ -pregnan- 3 ⁇ ,20 ⁇ -diol sul
  • the treatment of a pox virus-caused ailment according to the present embodiments may be combined with other treatment methods known in the art (i.e., combination therapy).
  • the method or use described herein may further involve additional treatment by any of the methodologies described above for treating pox virus manifestations.
  • the tellurium-containing compounds described above can thus be, for example, co-administered (simultaneously or separately) with additional agents for treating pox virus-caused ailments such as, for example, salicylic acid, betadine and the like.
  • the method described above can be accompanied by any of the physical treatment methods described above (e.g., laser therapy, cryosurgery and the like).
  • the tellurium-containing compounds can be provided to a subject either per se, or as part of a pharmaceutical composition where it is mixed with a pharmaceutically acceptable carrier.
  • a pharmaceutical composition which comprises a tellurium-containing compound as described herein and a pharmaceutically acceptable carrier.
  • a "pharmaceutical composition” refers to a preparation of one or more of the active ingredients described herein with other chemical components such as physiologically suitable carriers and excipients.
  • the purpose of a pharmaceutical composition is to facilitate administration of a compound to the subject treated.
  • pharmaceutically acceptable carrier refers to a carrier or a diluent that does not cause significant irritation to the subject and does not abrogate the biological activity and properties of the administered compound.
  • excipient refers to an inert substance added to a pharmaceutical composition to further facilitate administration of an active ingredient.
  • excipients examples include calcium carbonate, calcium phosphate, various sugars and types of starch, cellulose derivatives, gelatin, vegetable oils and polyethylene glycols. Techniques for formulation and administration of drugs may be found in
  • suitable routes of systemic administration may, for example, include oral, rectal, transmucosal, transnasal, intestinal or parenteral delivery, including intramuscular, subcutaneous and intramedullary injections as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal, or intraocular injections.
  • one may administer the composition in a local rather than systemic manner, for example, via injection of the preparation directly into a specific region of a patient's body.
  • compositions of the present embodiments may be manufactured by processes well known in the art, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or lyophilizing processes.
  • compositions for use in accordance with the present embodiments may be formulated in conventional manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries, which facilitate processing of the active ingredients (herein, tellurium-containing compounds) into preparations which, can be used pharmaceutically. Proper formulation is dependent upon the route of administration chosen.
  • the active ingredients may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hank's solution, Ringer's solution, or physiological salt buffer.
  • penetrants appropriate to the barrier to be permeated are used in the formulation.
  • penetrants are generally known in the art.
  • the compounds can be formulated readily by combining the active compounds with pharmaceutically acceptable carriers well known in the art.
  • Such carriers enable the compounds of the invention to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions, and the like, for oral ingestion by a patient.
  • Pharmacological preparations for oral use can be made using a solid excipient, optionally grinding the resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries if desired, to obtain tablets or dragee cores.
  • Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carbomethylcellulose; and/or physiologically acceptable polymers such as polyvinylpyrrolidone (PVP).
  • disintegrating agents may be added, such as cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate.
  • Dragee cores are provided with suitable coatings.
  • concentrated sugar solutions may be used which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, titanium dioxide, lacquer solutions and suitable organic solvents or solvent mixtures.
  • Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of active compound doses.
  • compositions which can be used orally, include push-fit capsules made of gelatin as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol.
  • the push-fit capsules may contain the active ingredients in admixture with filler such as lactose, binders such as starches, lubricants such as talc or magnesium stearate and, optionally, stabilizers.
  • the active ingredients may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols.
  • stabilizers may be added. All formulations for oral administration should be in dosages suitable for the chosen route of administration.
  • compositions may take the form of tablets or lozenges formulated in conventional manner.
  • the active ingredients for use according to the present embodiments are conveniently delivered in the form of an aerosol spray presentation from a pressurized pack or a nebulizer with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichloro-tetrafluoroethane or carbon dioxide.
  • a suitable propellant e.g., dichlorodifluoromethane, trichlorofluoromethane, dichloro-tetrafluoroethane or carbon dioxide.
  • the dosage unit may be determined by providing a valve to deliver a metered amount.
  • Capsules and cartridges of, e.g., gelatin for use in a dispenser may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch.
  • compositions described herein may be formulated for parenteral administration, e.g., by bolus injection or continuous infusion.
  • Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multidose containers with optionally, an added preservative.
  • the compositions may be suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents.
  • Pharmaceutical compositions for parenteral administration include aqueous solutions of the active preparation in water-soluble form. Additionally, suspensions of the active ingredients may be prepared as appropriate oily or water based injection suspensions.
  • Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acids esters such as ethyl oleate, triglycerides or liposomes.
  • Aqueous injection suspensions may contain substances, which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol or dextran.
  • the suspension may also contain suitable stabilizers or agents which increase the solubility of the active ingredients to allow for the preparation of highly concentrated solutions.
  • the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile, pyrogen-free water based solution, before use.
  • a suitable vehicle e.g., sterile, pyrogen-free water based solution
  • composition according to the present embodiments may also be formulated in rectal compositions such as suppositories or retention enemas, using, e.g., conventional suppository bases such as cocoa butter or other glycerides.
  • compositions suitable for use in context of the present embodiments include compositions wherein the active ingredients are contained in an amount effective to achieve the intended purpose. More specifically, a therapeutically effective amount means an amount of active ingredients effective to prevent, alleviate or ameliorate symptoms of disease or prolong the survival of the subject being treated.
  • the therapeutically effective amount or dose can be estimated initially from in vitro assays.
  • a dose can be formulated in animal models and such information can be used to more accurately determine useful doses in humans.
  • Toxicity and therapeutic efficacy of the active ingredients described herein can be determined by standard pharmaceutical procedures in vitro, in cell cultures or experimental animals.
  • the data obtained from these in vitro and cell culture assays and animal studies can be used in formulating a range of dosage for use in human.
  • the dosage may vary depending upon the dosage form employed and the route of administration utilized.
  • the exact formulation, route of administration and dosage can be chosen by the individual physician in view of the patient's condition. [See e.g., Fingl, et al., (1975) "The Pharmacological Basis of Therapeutics", Ch. 1 p.l].
  • dosing can be of a single or a plurality of administrations, with course of treatment lasting from several days to several weeks or until cure is effected or diminution of the disease state is achieved.
  • compositions formulated in a compatible pharmaceutical carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition.
  • compositions of the present embodiments may, if desired, be presented in a pack or dispenser device, such as an FDA approved kit, which may contain one or more unit dosage forms containing the active ingredient.
  • the pack may, for example, comprise a plastic foil, such as a blister pack.
  • the pack or dispenser device may be accompanied by instructions for administration.
  • the pack or dispenser may also be accommodated by a notice associated with the container in a form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals, which notice is reflective of approval by the agency of the form of the compositions or human or veterinary administration.
  • Such notice for example, may be of labeling approved by the U.S. Food and Drug Administration for prescription drugs or of an approved product insert.
  • a suitable route of administering the tellurium- containing compounds of the present embodiments include topical application.
  • the pharmaceutical composition is formulated in a form suitable for topical application on the treated area.
  • topical application describes application onto a biological surface, whereby the biological surface include, for example, an afflicted skin area or a mucosal membrane, as described herein.
  • compositions of the present embodiments may be formulated into any form typically employed for topical application.
  • the compositions of the present embodiments can be, for example, in a form of a cream, an ointment, a paste, a gel, a lotion, a milk, a suspension, an aerosol, a spray, a foam, a shampoo, a hair conditioner, a serum, a swab, a pledget, a pad, a patch and a soap.
  • Ointments are semisolid preparations, typically based on petrolatum or petroleum derivatives.
  • the specific ointment base to be used is one that provides for optimum delivery for the active agent chosen for a given formulation, and, preferably, provides for other desired characteristics as well (e.g., emolliency).
  • an ointment base should be inert, stable, nonirritating and nonsensitizing.
  • ointment bases may be grouped in four classes: oleaginous bases; emulsifiable bases; emulsion bases; and water-soluble bases.
  • Oleaginous ointment bases include, for example, vegetable oils, fats obtained from animals, and semisolid hydrocarbons obtained from petroleum.
  • Emulsifiable ointment bases also known as absorbent ointment bases, contain little or no water and include, for example, hydroxystearin sulfate, anhydrous lanolin and hydrophilic petrolatum.
  • Emulsion ointment bases are either water-in-oil (W/O) emulsions or oil-in-water (O/W) emulsions, and include, for example, cetyl alcohol, glyceryl monostearate, lanolin and stearic acid.
  • Preferred water-soluble ointment bases are prepared from polyethylene glycols of varying molecular weight.
  • Lotions are preparations that are to be applied to the skin surface without friction. Lotions are typically liquid or semiliquid preparations in which solid particles, including the active agent, are present in a water or alcohol base. Lotions are typically preferred for treating large body areas, due to the ease of applying a more fluid composition. Lotions are typically suspensions of solids, and oftentimes comprise a liquid oily emulsion of the oil-in-water type. It is generally necessary that the insoluble matter in a lotion be finely divided. Lotions typically contain suspending agents to produce better dispersions as well as compounds useful for localizing and holding the active agent in contact with the skin, such as methylcellulose, sodium carboxymethyl- cellulose, and the like.
  • Creams are viscous liquids or semisolid emulsions, either oil-in-water or water- in-oil.
  • Cream bases are typically water-washable, and contain an oil phase, an emulsif ⁇ er and an aqueous phase.
  • the oil phase also called the "internal" phase, is generally comprised of petrolatum and/or a fatty alcohol such as cetyl or stearyl alcohol.
  • the aqueous phase typically, although not necessarily, exceeds the oil phase in volume, and generally contains a humectant.
  • the emulsifier in a cream formulation is generally a nonionic, anionic, cationic or amphoteric surfactant. Reference may be made to Remington: The Science and Practice of Pharmacy, supra, for further information.
  • Pastes are semisolid dosage forms in which the bioactive agent is suspended in a suitable base. Depending on the nature of the base, pastes are divided between fatty pastes or those made from a single-phase aqueous gels.
  • the base in a fatty paste is generally petrolatum, hydrophilic petrolatum and the like.
  • the pastes made from single-phase aqueous gels generally incorporate carboxymethylcellulose or the like as a base. Additional reference may be made to Remington: The Science and Practice of Pharmacy, for further information.
  • Gel formulations are semisolid, suspension-type systems.
  • Single-phase gels contain organic macromolecules distributed substantially uniformly throughout the carrier liquid, which is typically aqueous, but also, preferably, contain an alcohol and, optionally, an oil.
  • Preferred organic macromolecules, i.e., gelling agents are crosslinked acrylic acid polymers such as the family of carbomer polymers, e.g., carboxypolyalkylenes that may be obtained commercially under the trademark CarbopolTM.
  • hydrophilic polymers such as polyethylene oxides, polyoxyethylene-polyoxypropylene copolymers and polyvinylalcohol.
  • cellulosic polymers such as hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, and methyl cellulose
  • gums such as tragacanth and xanthan gum; sodium alginate; and gelatin.
  • dispersing agents such as alcohol or glycerin can be added, or the gelling agent can be dispersed by trituration, mechanical mixing or stirring, or combinations thereof.
  • Sprays generally provide the active agent in an aqueous and/or alcoholic solution which can be misted onto the skin for delivery.
  • Such sprays include those formulated to provide for concentration of the active agent solution at the site of administration following delivery, e.g., the spray solution can be primarily composed of alcohol or other like volatile liquid in which the active agent can be dissolved.
  • the carrier evaporates, leaving concentrated active agent at the site of administration.
  • Foam compositions are typically formulated in a single or multiple phase liquid form and housed in a suitable container, optionally together with a propellant which facilitates the expulsion of the composition from the container, thus transforming it into a foam upon application.
  • Other foam forming techniques include, for example the "Bag-in-a-can" formulation technique.
  • compositions thus formulated typically contain a low-boiling hydrocarbon, e.g., isopropane.
  • a low-boiling hydrocarbon e.g., isopropane.
  • Application and agitation of such a composition at the body temperature cause the isopropane to vaporize and generate the foam, in a manner similar to a pressurized aerosol foaming system.
  • Foams can be water-based or hydroalcoholic, but are typically formulated with high alcohol content which, upon application to the skin of a user, quickly evaporates, driving the active ingredient through the upper skin layers to the site of treatment.
  • Skin patches typically comprise a backing, to which a reservoir containing the active agent is attached.
  • the reservoir can be, for example, a pad in which the active agent or composition is dispersed or soaked, or a liquid reservoir
  • patches typically further include a frontal water permeable adhesive, which adheres and secures the device to the treated region. Silicone rubbers with self-adhesiveness can alternatively be used. In both cases, a protective permeable layer can be used to protect the adhesive side of the patch prior to its use.
  • Skin patches may further comprise a removable cover, which serves for protecting it upon storage.
  • Examples of pharmaceutically acceptable carriers that are suitable for pharmaceutical compositions for topical applications include carrier materials that are well-known for use in the cosmetic and medical arts as bases for e.g., emulsions, creams, aqueous solutions, oils, ointments, pastes, gels, lotions, milks, foams, suspensions, aerosols and the like, depending on the final form of the composition.
  • Suitable carriers therefore include, without limitation, water, liquid alcohols, liquid glycols, liquid polyalkylene glycols, liquid esters, liquid amides, liquid protein hydrolysates, liquid alkylated protein hydrolysates, liquid lanolin and lanolin derivatives, and like materials commonly employed in cosmetic and medicinal compositions.
  • suitable carriers include, without limitation, alcohols, such as, for example, monohydric and polyhydric alcohols, e.g., ethanol, isopropanol, glycerol, sorbitol, 2-methoxyethanol, diethyleneglycol, ethylene glycol, hexyleneglycol, mannitol, and propylene glycol; ethers such as diethyl or dipropyl ether; polyethylene glycols and methoxypolyoxyethylenes (carbowaxes having molecular weight ranging from 200 to 20,000); polyoxyethylene glycerols, polyoxyethylene sorbitols, stearoyl diacetin, and the like.
  • the concentration of the tellurium-containing compound preferably ranges from about 0.01 weight percent and about 50 weight percents from the total weight of the composition.
  • the concentration of the tellurium-containing compound can be, for example, 0.01 weight percent, 0.05 weight percent, 0.1 weight percent, 0.5 weight percent, 1 weight percent, 2 weight percents, 3 weight percents, 4 weight percents or 5 weight percents.
  • the concentration of the tellurium-containing compound is 5 weight percents and higher and thus can be, for example, 5 weight percents, 6 weight percents, 7 weight percents, 8 weight percents, 9 weight percents or 10 weight percents.
  • 10 weight percents and higher can be, for example, 11 weight percents, 12 weight percents, 13 weight percents, 14 weight percents, 15 weight percents, 16 weight percents, 17 weight percents, 18 weight percents, 19 weight percents, 20 weight percents, 21 weight percents, 22 weight percents, 23 weight percents, 24 weight percents and up to 25 weight percents of the total weight of the composition.
  • the pharmaceutical composition is formulated as a cream, containing DMSO and Vaseline (for an exemplary composition, see, Example 1 hereinafter).
  • the pharmaceutical composition is formulated using propylene glycol and a polyethylene glycol-based cream (for an exemplary composition see, Example 2 hereinafter). Additional preferred compositions formulated for topical application of the tellurium-containing compounds described herein are described, for example, in U.S. Provisional Patent Application No. 60/843,402, by the present assignee, which is incorporated by reference as if fully set forth herein.
  • Each of the pharmaceutical compositions described herein may further comprise, according to an embodiment of the present invention, an additional active agent, as described hereinabove.
  • compositions described herein can optionally further comprise a variety of components that are suitable for providing the compositions with additional usage benefits.
  • conventional optional components are well known to those skilled in the art and are referred to herein as "ingredients".
  • these ingredients include humectants, deodorants, antiperspirants, sun screening agents, sunless tanning agents, hair conditioning agents, pH adjusting agents, chelating agents, preservatives, emulsifiers, occlusive agents, emollients, thickeners, solubilizing agents, penetration enhancers, anti-irritants, colorants, propellants (as described above) and surfactants.
  • compositions of the present embodiments can comprise humectants or moisturizing agents.
  • humectants that are usable in this context of the present embodiments include, without limitation, guanidine, glycolic acid and glycolate salts (e.g.
  • aloe vera in any of its variety of forms (e.g., aloe vera gel), allantoin, urazole, polyhydroxy alcohols such as sorbitol, glycerol, hexanetriol, propylene glycol, butylene glycol, hexylene glycol and the like, polyethylene glycols, sugars and starches, sugar and starch derivatives (e.g., alkoxylated glucose), hyaluronic acid, lactamide monoethanolamine, acetamide monoethanolamine and any combination thereof.
  • aloe vera gel e.g., aloe vera gel
  • allantoin urazole
  • polyhydroxy alcohols such as sorbitol, glycerol, hexanetriol, propylene glycol, butylene glycol, hexylene glycol and the like
  • polyethylene glycols sugars and starches
  • sugar and starch derivatives e.g., alkoxylated glucose
  • compositions of the present embodiments can further comprise a pH adjusting agent.
  • a pH adjusting agent is particularly preferred when the compositions are applied topically on the skin or in the genital areas.
  • the pH of these treated areas is typically lower than 6.0.
  • Suitable pH adjusting agents include, for example, one or more of adipic acids, glycines, citric acids, calcium hydroxides, magnesium aluminometasilicates, buffers or any combinations thereof.
  • deodorant agents that are usable in the context of the present embodiments include, without limitation, quaternary ammonium compounds such as cetyl-trimethylammonium bromide, cetyl pyridinium chloride, benzethonium chloride, diisobutyl phenoxy ethoxy ethyl dimethyl benzyl ammonium chloride, sodium N-lauryl sarcosine, sodium N-palmlthyl sarcosine, lauroyl sarcosine, N-myristoyl glycine, potassium N-lauryl sarcosine, stearyl, trimethyl ammonium chloride, sodium aluminum chlorohydroxy lactate, tricetylmethyl ammonium chloride, 2,4,4'-trichloro-2'- hydroxy diphenyl ether, diaminoalkyl amides such as L-lysine hexadecyl amide, heavy metal salts of citrate, salicylate
  • deodorant agents include, without limitation, odor absorbing materials such as carbonate and bicarbonate salts, e.g. as the alkali metal carbonates and bicarbonates, ammonium and tetraalkylammonium carbonates and bicarbonates, especially the sodium and potassium salts, or any combination of the above.
  • odor absorbing materials such as carbonate and bicarbonate salts, e.g. as the alkali metal carbonates and bicarbonates, ammonium and tetraalkylammonium carbonates and bicarbonates, especially the sodium and potassium salts, or any combination of the above.
  • Antiperspirant agents can be incorporated in the compositions of the present embodiments either in a solubilized or a particulate form and include, for example, aluminum or zirconium astringent salts or complexes.
  • Representative examples of sun screening agents usable in context of the present embodiments include, without limitation, p-aminobenzoic acid, salts and derivatives thereof (ethyl, isobutyl, glyceryl esters; p-dimethylaminobenzoic acid); anthranilates (i.e., o-amino-benzoates; methyl, menthyl, phenyl, benzyl, phenylethyl, linalyl, terpinyl, and cyclohexenyl esters); salicylates (amyl, phenyl, octyl, benzyl, menthyl, glyceryl, and di-pro-pyleneglycol esters); cin
  • sunless tanning agents usable in context of the present embodiments include, without limitation, dihydroxyacetone, glyceraldehyde, indoles and their derivatives.
  • the sunless tanning agents can be used in combination with the sunscreen agents.
  • the chelating agents are optionally added to the compositions of the present embodiments so as to enhance the preservative or preservative system.
  • Preferred chelating agents are mild agents, such as, for example, ethylenediaminetetraacetic acid (EDTA), EDTA derivatives, or any combination thereof.
  • Suitable preservatives that can be used in the context of the present embodiments include, without limitation, one or more alkanols, disodium EDTA (ethylenediamine tetraacetate), EDTA salts, EDTA fatty acid conjugates, isothiazolinone, parabens such as methylparaben and propylparaben, propylene glycols, sorbates, urea derivatives such as diazolindinyl urea, or any combinations thereof.
  • Suitable emulsifiers that can be used in the context of the present embodiments include, for example, one or more sorbitans, alkoxylated fatty alcohols, alkylpolyglycosides, soaps, alkyl sulfates, monoalkyl and dialkyl phosphates, alkyl sulphonates, acyl isothionates, or any combinations thereof.
  • Suitable occlusive agents that can be used in the context of the present embodiments include, for example, petrolatum, mineral oil, beeswax, silicone oil, lanolin and oil-soluble lanolin derivatives, saturated and unsaturated fatty alcohols such as behenyl alcohol, hydrocarbons such as squalane, and various animal and vegetable oils such as almond oil, peanut oil, wheat germ oil, linseed oil, jojoba oil, oil of apricot pits, walnuts, palm nuts, pistachio nuts, sesame seeds, rapeseed, cade oil, corn oil, peach pit oil, poppyseed oil, pine oil, castor oil, soybean oil, avocado oil, safflower oil, coconut oil, hazelnut oil, olive oil, grape seed oil and sunflower seed oil.
  • petrolatum mineral oil
  • beeswax silicone oil
  • lanolin and oil-soluble lanolin derivatives saturated and unsaturated fatty alcohols such as behenyl alcohol
  • hydrocarbons
  • Suitable emollients that can be used in the context of the present embodiments include, for example, dodecane, squalane, cholesterol, isohexadecane, isononyl isononanoate, PPG Ethers, petrolatum, lanolin, safflower oil, castor oil, coconut oil, cottonseed oil, palm kernel oil, palm oil, peanut oil, soybean oil, polyol carboxylic acid esters, derivatives thereof and mixtures thereof.
  • Suitable thickeners that can be used in the context of the present embodiments include, for example, non-ionic water-soluble polymers such as hydroxyethylcellulose (commercially available under the Trademark Natrosol® 250 or 350), cationic water- soluble polymers such as Polyquat 37 (commercially available under the Trademark Synthalen® CN), fatty alcohols, fatty acids and their alkali salts and mixtures thereof.
  • non-ionic water-soluble polymers such as hydroxyethylcellulose (commercially available under the Trademark Natrosol® 250 or 350), cationic water- soluble polymers such as Polyquat 37 (commercially available under the Trademark Synthalen® CN), fatty alcohols, fatty acids and their alkali salts and mixtures thereof.
  • solubilizing agents that are usable in this context of the present embodiments include, without limitation, complex-forming solubilizers such as citric acid, ethylenediamine-tetraacetate, sodium meta-phosphate, succinic acid, urea, cyclodextrin, polyvinylpyrrolidone, diethylammonium-ortho-benzoate, and micelle- forming solubilizers such as TWEENS and spans, e.g., TWEEN 80TM.
  • complex-forming solubilizers such as citric acid, ethylenediamine-tetraacetate, sodium meta-phosphate, succinic acid, urea, cyclodextrin, polyvinylpyrrolidone, diethylammonium-ortho-benzoate, and micelle- forming solubilizers such as TWEENS and spans, e.g., TWEEN 80TM.
  • solubilizers that are usable for the compositions of the present embodiments are, for example, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene n-alkyl ethers, n- alkyl amine n-oxides, poloxamers, organic solvents, phospholipids and cyclodextrines.
  • Suitable penetration enhancers usable in context of the present embodiments include, but are not limited to, dimethylsulfoxide (DMSO), dimethyl formamide (DMF), allantoin, urazole, N,N-dimethylacetamide (DMA), decylmethylsulfoxide (C 10 MSO), polyethylene glycol monolaurate (PEGML), propylene glycol (PG), propylene glycol monolaurate (PGML), glycerol monolaurate (GML), lecithin, the 1 -substituted azacycloheptan-2-ones, particularly l-n-dodecylcyclazacycloheptan-2-one (available under the trademark Azone R TM from Whitby Research Incorporated, Richmond, Va.), alcohols, and the like.
  • the permeation enhancer may also be a vegetable oil. Such oils include, for example, safflower oil, cottonseed oil and corn oil.
  • Suitable anti-irritants that can be used in the context of the present embodimentsn include, for example, steroidal and non steroidal anti-inflammatory agents or other materials such as aloe vera, chamomile, alpha-bisabolol, cola nitida extract, green tea extract, tea tree oil, licoric extract, allantoin, caffeine or other xanthines, glycyrrhizic acid and its derivatives.
  • steroidal and non steroidal anti-inflammatory agents or other materials such as aloe vera, chamomile, alpha-bisabolol, cola nitida extract, green tea extract, tea tree oil, licoric extract, allantoin, caffeine or other xanthines, glycyrrhizic acid and its derivatives.
  • compositions of the present embodiments may be packed or presented in any convenient way.
  • they may be packed in a tube, a bottle, or a pressurized container, using techniques well known to those skilled in the art and as set forth in reference works such as Remington's Pharmaceutical Science 15 th Ed. It is preferred that the packaging is done in such a way so as to minimize contact of the unused compositions with the environment, in order to minimize contamination of the compositions before and after the container is opened.
  • compositions are preferably identified in print, in or on the packaging material, for use in the treatment an ailment caused by a pox virus, as described hereinabove.
  • FIG. 1A A female patient diagnosed with Molluscum contagiosum (MC), applied topically ASlOl 20 % cream (20 % w/v ASlOl in 5 % DMSO in Vaseline cream) to the lesions twice daily for a period of 14 weeks.
  • Figure IA presents the patient's infected area prior to treatment.
  • Figure IB within 2 weeks of treatment, a change of skin color was noticed around the MC infected area.
  • Figure 1C the disease was almost cleared after 3.5 months treatment, leaving no scars.
  • FIG. 1 A 44-years old female patient diagnosed with Molluscum contagiosum (MC), applied topically ASlOl 20 % cream (12 % w/w ASlOl in 5 % Propylene glycol in Polyethylene glycol based cream) to the lesions twice daily for a period of 4 weeks.
  • Figure 2A presents the patient's infected area prior to treatment.
  • Figures Ib and Ic within 2 weeks treatment a gray to black staining was noticed at some of the MC lesion along with reduction of size (See arrows in Figures 2B and 2C).
  • Within almost 4 weeks treatment some lesions were cleared, leaving no scars. Treatment was terminated after 27 days per patient's request.

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Abstract

L'invention concerne des procédés et des compositions utilisant des composés contenant du tellure tels que l'AS101 pour lutter contre des poxvirus tels que le virus du Molluscum contagiosum.
PCT/IL2008/001538 2007-11-23 2008-11-23 Procédés et compositions de traitement de poxvirus au moyen de composés contenant du tellure WO2009066301A2 (fr)

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CN107427478A (zh) * 2015-02-26 2017-12-01 费拉姆达有限公司 用于治疗血管生成疾病和紊乱的组合物和组合
CN112426398A (zh) * 2020-12-22 2021-03-02 广州天翼化妆品有限公司 一种具有淡化痘印作用的祛痘组合物及其制备方法
WO2023230472A1 (fr) * 2022-05-23 2023-11-30 The Trustees Of The University Of Pennsylvania Inhibiteurs de l'infection par le molluscum contagiosum et méthodes les utilisant

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WO2006030438A2 (fr) * 2004-09-17 2006-03-23 Biomas Ltd. Utilisation de composes a base de tellure pour inhiber l'enzyme de conversion de l'interleukine

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WO2006030438A2 (fr) * 2004-09-17 2006-03-23 Biomas Ltd. Utilisation de composes a base de tellure pour inhiber l'enzyme de conversion de l'interleukine

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107427478A (zh) * 2015-02-26 2017-12-01 费拉姆达有限公司 用于治疗血管生成疾病和紊乱的组合物和组合
CN112426398A (zh) * 2020-12-22 2021-03-02 广州天翼化妆品有限公司 一种具有淡化痘印作用的祛痘组合物及其制备方法
WO2023230472A1 (fr) * 2022-05-23 2023-11-30 The Trustees Of The University Of Pennsylvania Inhibiteurs de l'infection par le molluscum contagiosum et méthodes les utilisant

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