WO1994009798A1 - Melanges ou complexes contenant du calcium et du sulfate - Google Patents

Melanges ou complexes contenant du calcium et du sulfate Download PDF

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Publication number
WO1994009798A1
WO1994009798A1 PCT/US1993/010489 US9310489W WO9409798A1 WO 1994009798 A1 WO1994009798 A1 WO 1994009798A1 US 9310489 W US9310489 W US 9310489W WO 9409798 A1 WO9409798 A1 WO 9409798A1
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WIPO (PCT)
Prior art keywords
pharmaceutically acceptable
acceptable composition
sulfate
composition according
calcium
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PCT/US1993/010489
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English (en)
Inventor
Ralph M. Hart
Herman L. Jones
Veronica Lee Egelkrout
Sohail Malik
Margaret A. Kenny
Bernard Loev
James P. Harnisch
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C-P Technology Limited Partnership
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Application filed by C-P Technology Limited Partnership filed Critical C-P Technology Limited Partnership
Priority to AU55895/94A priority Critical patent/AU5589594A/en
Priority to EP94901234A priority patent/EP0666750A1/fr
Priority to JP6511380A priority patent/JPH08502976A/ja
Publication of WO1994009798A1 publication Critical patent/WO1994009798A1/fr

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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
    • 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
    • A61K33/30—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
    • 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
    • A61K33/32—Manganese; Compounds thereof
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the present invention relates generally to novel compositions and methods suitable for treatment of disease, injury and other disorders. More specifically, the invention relates to inorganic calcium-containing and sulfate- containing compositions, methods of isolation, methods of synthesis, and pharmaceutical compositions suitable for accelerating wound healing, providing relief of pain, itch or inflammation, reducing abnormal proliferative cell growth, or providing anti-fungal, anti-viral, or anti-bacterial activity.
  • methotrexate while generally effective for treating epidermal conditions when administered orally, is rarely administered orally for fear of hepatic or bone marrow toxicity.
  • Topical application of methotrexate has been deemed ineffective.
  • topical application of 5-fluorouracil may be an effective treatment for psoriasis, it is generally considered to be unacceptably irritating.
  • Steroid therapy while effective, has so many side effects that prolonged use is discouraged.
  • Photochemotherapy with psoralens and ultraviolet light, or PUVA psoralens and UV treatment
  • PUVA psoralens and UV treatment
  • compositions of the present invention are therefore directed to pharmaceutical preparations and methods for treating a variety of disorders.
  • the present invention provides novel calcium-containing and sulfate-containing compositions, and analogs and derivatives thereof, that function medicinally, therapeutically or pharmaceutically in the treatment of various diseases, injuries and conditions.
  • novel calcium-containing and sulfate-containing compositions of the present invention have demonstrated significant therapeutic benefit.
  • a first class of inorganic compositions comprises mixtures of a calcium-containing component and a sulfate-containing component. Mixtures of calcium sulfate and potassium sulfate are especially preferred.
  • a second class of inorganic compositions includes complexes of a calcium-containing or potassium-containing component and a sulfate-containing component.
  • Syngenite and apthitalite are especially preferred complexes and may be administered as a mixture with one or more of the above- mentioned calcium-containing or sulfate-containing components.
  • a mixture of syngenite and calcium sulfate, for example, is especially preferred therapeutic composition of the present invention.
  • the compositions of the present invention may also comprise one or more of the following elements, which may be present in elemental form, ionic form, as a salt or chelate, or in any other form: sodium; magnesium; silicon; sulfur; chlorine; potassium; strontium; zinc; copper; nickel; and manganese.
  • the inorganic compositions of the present invention can be isolated from natural materials, such as peat, using the extraction and purification procedures disclosed herein.
  • the inorganic compositions may alternatively be produced by combining and/or synthesizing the constituent components. Novel methods for synthesizing high purity syngenite are also disclosed herein.
  • the inorganic compositions of the present invention have produced therapeutic results in a variety of medicinal, pharmaceutical, and therapeutic applications in warm-blooded animals. Those applications may be characterized generally as promoting wound healing, treatment of pain, inflammation, itch, and inhibition of abnormal proliferative cell growth. Additionally, the inorganic compositions have demonstrated anti-fungal, anti-bacterial, anti-rickettsial and anti-viral properties and may also be used in cosmetic preparations.
  • Topical delivery systems are effective and are generally preferred for most applications of the pharmaceutical composition of the present invention.
  • Topical formulations may be produced by dissolving or combining the inorganic compositions of the present invention in an aqueous or nonaqueous carrier. Suitable carriers are well known and are described below.
  • Figure 1 shows an elution profile of a 0.5-30Kd fraction from a peat extract purified by High Performance Liquid Chromatography (HPLC) according to the methods described herein.
  • Figure 2 illustrates the X-ray powder diffraction analysis of standard gypsum published by the Joint Committee on Powder Diffraction Standards ("JCPDS") Library.
  • JCPDS Joint Committee on Powder Diffraction Standards
  • Figure 3 illustrates the X-ray powder diffraction analysis for syngenite published by the JCPDS Library.
  • Figure 4 shows an x-ray powder diffraction analysis spectrum identifying gypsum (CaS0 4 -2H 2 0) in a peat extract sample using X-ray powder diffraction analysis.
  • Figure 5 shows a spectrum identifying gypsum (CaS0 4 *2H 2 0) and syngenite (CaSCvK 2 S0 4 -H 2 0) in a peat extract sample using X-ray powder diffraction analysis.
  • Figure 6 depicts a spectrum identifying syngenite and apthitalite (K 3 Na(S0 4 ) 2 ) in a peat extract sample using X-ray powder diffraction analysis.
  • Figure 7 illustrates an X-ray powder diffraction analysis spectrum for syngenite produced synthetically according to the methods described herein.
  • compositions of the present invention comprise a mixture and/or complex of a calcium-containing or potassium-containing component and one or more sulfate- containing components in a pharmaceutically acceptable formulation that is effective in the treatment of various diseases, injuries, symptoms or other disorders.
  • All references to "components" in this application, in whatever form, are understood to include associated, dissociated, ionic, neutral, elemental, salt, hydrated, and other forms of the constituents.
  • a calcium sulfate component may be present in an associated form as a neutral or ionic species; as part of a larger complex; or in a dissociated form in which calcium and sulfate are present as distinct, non-complexed neutral or ionic species.
  • composition also contemplates mixtures of associated, dissociated and complexed constituents.
  • mixture connotes a composition wherein the constituent components are present in their associated, dissociated, elemental, ionic, salt, hydrated and other forms.
  • a composition comprising a mixture of calcium sulfate and another sulfate- containing component, such as potassium sulfate, may comprise calcium sulfate and potassium sulfate typically not physically bonded to one another but rather in neutral or ionic forms and/or partially, substantially or completely dissociated into their respective species.
  • a “mixture” of two components may be substantially or entirely dissociated. It is anticipated that the precise form(s) of the individual components in a mixture will vary depending, for example, upon the relative quantity of each component, the use of aqueous or non-aqueous carriers, and the desired pharmaceutical applications or methods of treatment.
  • complex connotes a composition wherein individual constituents are associated, i.e.. bound to one another covalently or non-covalently as a result of hydrogen bonding or other intra-molecular forces. Complexes may be present in neutral, ionic, salt, hydrated or other forms.
  • Suitable mixtures of a calcium-containing component and one or more sulfate-containing components include, for example, mixtures of calcium sulfate with another sulfate- containing component having a constituent chosen from one or more of the following: magnesium, potassium, aluminum, sodium, silicon, sulfur, chlorine, calcium, silicon, strontium, zinc, copper, nickel or manganese. Calcium sulfate is a preferred calcium-containing component.
  • Preferred sulfate-containing components include: MgS0 4 , K 2 S0 4 , A1 2 (S0 4 ) 3 , 2CaS0 4 -MgS0 4 -K 2 S0 4 -2H 2 0, CaS0 4 •K 2 S0 4 • H 2 0, 3CaO-Al 2 0 3 -CaS0 4 -32H 2 0, CaS0 4 -Na 2 S0 4 , Na 2 SO 4 -10H 2 O and K 2 S0 4 '5CaS0 4 .
  • Mixtures of calcium sulfate with potassium sulfate and/or syngenite (CaS0 4 *K 2 S0 4 *H 2 0) are especially preferred.
  • K 3 Na(S0 4 ) 2 , NaAlSi 3 0 g , and/or KAlSi 3 0 8 may also be incorporated in the mixtures.
  • the mixtures are combined in a carrier, as described below, and administered for treatment.
  • compositions of the present invention may also comprise a complex of a calcium- containing or potassium-containing components with one or more sulfate-containing components.
  • Syngenite (CaS0 4 -K 2 S0 4 -H 2 0) is a preferred complex.
  • Other complexes, such as K 3 Na(S0 4 ) 2 may also be used.
  • a complex of calcium sulfate with one or more other sulfate-containing components, such as syngenite is administered in a carrier, in the form of a mixture with another sulfate-containing component.
  • the mixture of syngenite and calcium sulfate is an especially preferred composition.
  • Syngenite with other sulfates such as MgS0 4 , K 2 S0 4 , A1 2 (S0 4 ) 3 ; 2CaS0 4 -MgS0 4 -K 2 S0 4 -2H 2 0, 3CaO-Al 2 0 3 -CaS0 4 -32H 2 0, CaS0 4 -Na 2 S0 4 , Na 2 SO 4 -10H 2 O and K 2 S0 4 -5CaS0 4 , may also be used.
  • K 3 Na(S0 4 ) 2 , NaAlSi 3 0 8 and/or KAlSi 3 0 8 may also be incorporated in the mixtures.
  • compositions of the present invention may be derived from natural sources, such as peat, or they may be derived synthetically.
  • natural sources such as peat
  • the biologically active inorganic compositions of the present invention were initially discovered in peat extracts, and considerable data relating to naturally derived peat materials has been collected.
  • the inorganic preparations comprise an alkaline, aqueous or organic, or mixture thereof, extract of peat prepared according to the methods disclosed herein.
  • peat refers generally to microbial degradation products of biomass, including peat and peat-related substances such as minerals, coal and coal-derived materials, including leonardite and lignite, and humic and fulvic acid preparations.
  • Peat extracts are prepared by extracting peat with aqueous solutions, organic solutions or water-miscible organic solvents at temperatures from below room temperature up to the boiling point of the solvents, but preferably below the boiling point of the solvent. Extraction at room temperature is quite suitable; however, the speed of extraction and total amount of active composition isolated are generally enhanced by carrying out the extraction treatment at elevated temperatures.
  • purified peat preparations are prepared from Bonaparte peat. Bonaparte peat is hypnum peat obtained from Bonaparte Meadows, a peat bog near Bonaparte Lake, Washington, U.S.A. More specifically, the bog is located approximately 25 miles east of Tonasket, Washington, U.S.A., in Sees. 17, 20 and 29, T. 38 N. , R. 30E, in Eastern Okanogan County.
  • aqueous solvents particularly those containing alkali metals, alkaline earth metals and ammonium hydroxides, carbonates and bicarbonates, are preferred for peat extraction.
  • Biologically active factors contained in the peat preparation are separated or removed from the residual solids by customary methods such as filtration, ultrafiltration, centrifugation, and decantation.
  • Peat preparations are complex mixtures which contain inorganic and organic constituents that may have molecular masses as large as several hundred thousand daltons.
  • Various fractions of purified peat preparations have been found to exhibit biological activity and are referred to herein according to their molecular mass or fraction or sample number.
  • 10-30Kd peat preparation refers to a peat preparation comprising constituents having a molecular mass between about 10,000 and 30,000 daltons.
  • Various fractions isolated from peat differ in the profile of their biological activities.
  • a peat extract identified as peak #11 contains a high level of biological activity.
  • samples #44 and #46, described in Example 4 exhibit significant biological activity.
  • Biologically active constituents of fractionated peat preparations were identified as CaS0 4 -2H 2 0 (gypsum), CaS0 4 -K 2 S0 4 -H 2 0 (syngenite) and K 3 Na(S0 4 ) 2 (apthitalite) by X- ray powder diffraction analysis.
  • Each biologically active composition was identified by comparison of an X-ray powder diffraction spectrum of a fractionated peat extract to a standard spectrum of the Joint Committee of Powder Diffraction Standards (JCPDS) Library. The standard and experimental X-ray power diffraction spectra are illustrated in Figs. 2-6.
  • the elemental constituents present in a peat extract were identified by qualitative analysis using high resolution X-ray fluorescence spectrometry (XRF) .
  • XRF X-ray fluorescence spectrometry
  • the following elemental constituents were identified: sodium; magnesium; silicon; chlorine; potassium; calcium; strontium; zinc; copper; nickel; and manganese. It is believed that one or more of these elemental constituents contribute to the biological activity of peat preparations.
  • compositions derived from peat may also be derived from other sources.
  • High purity calcium sulfate and hydrated forms of calcium sulfate including CaS0 4 -2H 2 0 (gypsum) , CaS0 4 'J_ ⁇ 2 0, and the like, are commercially available from a variety of sources.
  • Potassium sulfate (K 2 S0 4 ) and many of the other sulfate-containing compositions described herein are likewise commercially available.
  • Others of the inorganic complexes disclosed herein may not be commercially available but are available from natural sources.
  • K 3 Na(S0 4 ) 2 also known as apthitalite, is not commercially available, but may be obtained as a naturally occurring mineral or from other natural sources, i.e., peat, or it may be produced in the lab according to the protocal of Yanat'eva, O.K., et al., Chem. Abstr. 91 (2): 7031y (1979) .
  • Components such as 2CaS0 4 « MgS0 4 -K 2 S0 4 -2H 2 0, 3CaO-Al 2 0 3 -3CaS0 4 -32H 2 0, CaS0 4 -Na 2 S0 4 , Na 2 S0 4 •10H 2 0, NaAlSi 3 0 8 and KAlSi 3 0 8 are not readily commercially available, but they may be obtained as naturally occurring minerals.
  • Syngenite (CaS0 4 -K 2 S0 4 *H 2 0) , also referred to as the double salt of gypsum, is one of the preferred calcium- and sulfate-containing complexes, but it is not available commercially at high purity levels. Syngenite may be obtained as an occurring mineral or from other natural sources, such as mineral deposits or peat. Applicants are aware of the two following reported syntheses for syngenite: Calistru, C, et al., Chem. Abstr. 106 (5.) :31984k (1986); and Yunusova, Z., et al., Chem. Abstr. 114 (10) :84755h (1990), but could not produce high purity syngenite according to the published methods. Applicants therefore developed the following novel protocol for synthetic production of syngenite.
  • Syngenite can be synthesized, very expediently and economically, by mixing an aqueous solution of potassium sulfate with an aqueous solution of calcium sulfate. A molar excess of potassium sulfate is preferably provided to the reaction mixture. According to especially preferred embodiments, a molar access of potassium sulfate of about 3 fold to about 10 fold is provided in the reaction mixture.
  • a detailed protocol for syngenite synthesis is provided in Example 6. That synthetic protocol yielded pure (>90%) syngenite.
  • compositions of the present invention will vary according to the type and location of the disease, injury or condition.
  • Potentially useful methods of administration include topical application of preparation in an suitable aqueous or non- aqueous carrier, injection of the preparation in a carrier, and oral administration.
  • the preparations may also be administered in a solid form, such as a powder or tablet.
  • the novel compositions are preferably used topically, but may be used orally or parenterally, either individually or in a pharmaceutically acceptable composition further comprising a pharmaceutically acceptable, and preferably inert, carrier or diluent.
  • pharmaceutically acceptable carriers and diluents contemplates any carrier or other substance that is combined with the biologically active compositions for use in any one of the enumerated methods of administration.
  • Suitable aqueous and non-aqueous carriers are well known in the art. In general, any liquid, cream, gel or similar substance that does not appreciably react with the active ingredients and which is non-irritating is suitable. In a preferred embodiment mixtures and complexes of the present invention are administered in an aqueous carrier, but various non-aqueous solvents or emulsions may also be used as carriers. Suitable carriers include, but are not limited to: 1,2,3, -trihydroxypropanol, triethanolamine, EDT, and the like. In addition, the preparations may also contain fragrances, colors, self-sterilizing agents, odor controllers and thickeners such as natural gums and/or stabilizers.
  • the biologically active constituents e.g.. syngenite and/or a calcium sulfate complex
  • a pharmaceutic preparation in an amount of at least about 0.00001% to about 20%, typically about 0.001% to 2%, and preferably about 0.01% to 0.5% by weight.
  • concentrations of biologically active constituents such as syngenite and/or the calcium sulfate complex may be limited by their solubility in a given pharmaceutical carrier or diluent. In such a case, the limit of solubility can be the preferred solubility. However, higher percentages of biologically active constituents may be obtained by preparing a slurry, or other mixture wherein not all of the mixture or complex is in solution.
  • the inorganic compositions disclosed herein demonstrate therapeutic utility for a broad range of human and veterinary indications, including: promotion of wound healing; reduction of pain, itch and inflammation; inhibition of abnormal cell proliferation; and infections caused by fungal, bacterial, rickettsial or viral agents. More particularly, as described in the appended examples, the inorganic compositions disclosed herein have been found to be active for the treatment of skin disorders such as psoriasis and eczema, acne, seborrheic keratosis and actinic keratosis. They are very effective in treating dermatitis, burns and open wounds and provide pain relief from any number of conditions.
  • the inorganic compositions are also useful in the prevention and treatment of herpes, conjunctivitis and athlete's foot, and may be efficacious in the treatment of AIDS.
  • inorganic compositions of the present invention effectively treat diseases which include multiple drug resistance, cystic fibrosis, cancers, asthma, rheumatoid arthritis and other inflammatory disorders.
  • Cancers for which the inventive compositions are effective include squamous call carcinomas, epithelial carcinomas, bladder tumors and lung tumors.
  • the compositions of the present invention are also suitable for use in cosmetic applications. Administration of a therapeutically effective amount of the compositions is preferably begun at the first indication of pain or other disorder, and continued until symptoms disappear or cease to respond to treatment.
  • a “therapeutically effective amount” means an amount effective to alleviate one or more symptoms, or reduce or ameliorate one or more causes of the disease, injury or disorder.
  • the SBE or SE may be used "as is, " but, a purified preparation is desirable for many purposes and was provided using ultrafiltration techniques.
  • Potassium hydroxide (66.4 g) was added with stirring to 88 kilos of Bonaparte peat (approximately 53 kg dry-weight) suspended in 190 liters water. After 24 hours the solids were allowed to settle. The supernatant liquid was separated by decanting or filtering. This solution corresponds to SE. Upon lyophilization, this solution has been found to yield an average of 0.4 mg/ml solids.
  • the SE was ultrafiltered through an Amicon polysulfone 30 Kd filter, which retained material of molecular mass greater than 30,000 daltons
  • the retained material (>30Kd) typically contained about 0.2 mg/ml solids.
  • a 25 liter portion of this ⁇ 30Kd solution was ultrafiltered through another Amicon filter which retained materials of molecular mass greater than lOKd to give 250 ml of a retentate containing an average of 0.1 mg/ml solids.
  • Peat was extracted, purified by ultrafiltration, and then further purified using HPLC.
  • HPLC HPLC-based reverse phase liquid chromatography
  • 65 kilograms of peat and 264 grams of KOH were stirred in 760 liters of water. After 24 hours the solids were allowed to settle. The supernatant liquid was filtered or decanted to produce the "Standard Extract.”
  • the standard extract was ultrafiltered through an Amicon hollow filter cartridge 30Kd to yield a filtrate comprising 740 liters containing material of molecular mass ⁇ 30Kd.
  • a gradient of solvents beginning with Methanol (100%) and gradually changing to end with deionized water (100%) was passed through the column at a flow rate of 1.5 ml/min.
  • the eluate was scanned by a UV detector set at a wave length 254 nm.
  • Peak #11 contains a high concentration of biologically active material. Peak #11 eluted from 9 to 11 minutes in the HPLC system described above.
  • Figure 1 illustrates the HPLC results and identifies peak #11.
  • X-ray powder diffraction analysis identifies the significant compositions in peak #11 as gypsum [CaS0 4 -2H 2 0] and syngenite [CaS0 4 -K 2 S0 4 -H 2 0] ; and apthitalite [K 3 Na(S0 4 ) 2 ] .
  • Figures 2 and 3 illustrate the x-ray powder diffraction standard spectra for gypsum and syngenite, respectively, published by the JCPDS Library.
  • Figures 4 and 5 illustrate spectra identifying gypsum (Figure 4) and both gypsum and syngenite (Figure 5) in the peat sample.
  • Figure 6 illustrates a spectrum identifying both syngenite and apthitalite in a peak #11 peat sample.
  • Example 4 Alternate Peat Purification Preparation An aqueous solution of peat was prepared and allowed to stand unfiltered for a time period sufficient for a film to form on the surface, usually at least 1 week. 1e film was carefully skimmed from the surface and mixed with water. The resulting film solution was ultrafiltered through a lKd Amicon spiral wound cartridge to dryness and the >lKd fraction was discarded. The solution ⁇ lKd was then filtered through an Amicon spiral wound cartridge with a nominal ⁇ .5Kd exclusion. The retentate was lyophilized to dryness, reconstituted in water and called Sample #44. The filtrate of ⁇ .5Kd was concentrated by lyophilization and called Sample #46.
  • Samples #44 and #46 yield fractions with the same HPLC retention times as peak #11 from the SE, and similar proportion of calcium sulfate (gypsum) as the major aspect of their chemical compositions.
  • Sample #46 when repurified by HPLC, eluted as a single peak that comprised two compounds, of which syngenite was the major component.
  • the inorganic compositions administered to humans patients in the following studies were derived from natural peat sources unless otherwise indicated.
  • the peat preparation administered to human patients was isolated from Bonaparte peat and purified as set forth in Example 2. Unless otherwise indicated, an aqueous 0.2% solution by weight of the 10-30Kd peat preparation ("Peat Preparation") was applied topically three times a day.
  • Other peat fractions, including a 3-30Kd fraction of standard extract, peak #11 and/or samples #44 and #46 were applied topically two and occasionally three times daily in a liquid carrier in the trials indicated.
  • Aqueous and emollient peat preparations were administered.
  • 10-30Kd Peat Preparation was well tolerated without irritation or staining. Smaller, more recent and less thick plaques showed early improvement, i.e., within two weeks. The psoriasis plaques were less responsive when chronic and well established. The improvement in erythema and scale of the psoriasis plaques was seen in three of the five patients and improvement in scales was seen in four of the five patients. One patient had complete clearing of all his plaques except for a small residual area on the elbow. The 10-30Kd peat extract was equal in efficacy to a potent steroid applied topically.
  • Atopic Dermatitis Patients 15-20 Human patients 15-20 having chronic atopic dermatitis of the face were treated with 10-30 Kd Peat Preparation. All were experiencing intense pruritus of the dry facial eczema along with increasing lichenification resulting from the rubbing and inflammation. One also had similar severity in his hands/arms along with excoriation. In addition to the emollients, all were using either Locoid or Elocon cream twice daily on the facial eczema without control. All were showing signs of steroid atrophy.
  • the pruritus relief was immediate and the dermatitis cleared over 4-5 days. Remission of several weeks was observed in two patients and three were eventually maintained with once daily application. One patient completely cleared of active dermatitis and continued treatment for several months. After a three-week hiatus, treatment was resumed, but without the same response. This patient could not fully control the condition solely using a composition comprising peak #11. Twice weekly Locoid cream was required along with daily administration of peat extract to control the pruritic dermatitis.
  • Patient 21 had four wisdom teeth extracted. Two of the teeth were seriously impacted. The patient was given a prescription for hydrocodone (a narcotic analgesic) and released. The patient was in a great deal of pain and, instead of taking the hydrocodone, he swished a few milliliters of a solution comprising peak #11 around in his mouth. The pain was relieved instantaneously. The patient repeated the administration at 30-minute intervals for about two hours. Administration at 2-hour intervals seemed to be sufficient thereafter. This patient continued with this schedule for approximately two days and was essentially pain free.
  • hydrocodone a narcotic analgesic
  • Burn - Patient 22 Patient 22 sustained second and third degree burns over most of three fingers on her right hand. The burns were caused by contact with a flame and by burning nylon that stuck to her fingers. The Emergency Room doctor diagnosed the burns, cut away the burned nylon and skin, and applied sulfadiazine. The sulfadiazine was later removed and a 3-30Kd peat preparation was applied. The patient dressed the wound at least twice daily with bandages soaked with the 3-30Kd peat preparation. The pain abated almost immediately upon application of the preparation and the wounds remained largely pain-free. Within 3 weeks, the patient's fingers were healed, but still pink. After 2 more weeks, there were no indications of scars or wound marks of any sort; the skin of the fingers appeared healthy in all respects.
  • Patient 23 had a laminectomy and subsequently experienced spasms in his lower back. After eight months, the patient was treated with a 10-30Kd Peat Preparation in a cream carrier and he was immediately relieved of pain. Patient 23 also has a long-lasting problem with his feet, which was reported to be jungle rot and which caused unbearable itching and open lesions. After applying the 10-30Kd Purified Peat Preparation cream to his feet, the pain and itching subsided and the odor disappeared.
  • Chronic Arthritis - Patient 24 Patient 24 had suffered from chronic arthritis for about twelve years and consulted several doctors and chiropractors over these years. Patient 24 was treated with various oral drugs and injections of cortisone, but none of these treatments provided relief. Patient 24 applied a 3-30Kd Peat Preparation topically to an inflamed foot, knee and shoulder twice daily. Within 5 days, there was significant relief in all areas. Patient 24 was able to discontinue use after about 10 days.
  • Patient 25 had eczema for approximately 8 years. He had been unresponsive to other anti-eczema therapy and the eczema had never completely disappeared nor been effectively treated. He applied a solution comprising 10-30Kd Peat Preparation (2mg/ml) diluted with 15 ml water and 15 ml of a 0.004% solution of calcium gluconate (final pH 7.3) to well-established spots of eczema. Skin irritation (burning) , thought to be caused by the calcium gluconate, occurred for approximately 30 minutes. Applications were continued twice daily for about 10 days. The affected area became quite red; however, all lesions disappeared within 8 days. The redness disappeared after treatment with Lidex cream for 2 days, leaving only slight discoloration of the skin. No lesions have reappeared in the same locations, but the eczema continued to present itself in different locations. The new eczema spots were treated with a peat preparation that contained no calcium gluconate. These treatments produced positive results.
  • Patient 26 applied a 10-30Kd Peat Preparation to eczema covering both legs between his ankles and knees. Itching was so severe when the patient was in contact with warm or hot water that taking a shower was almost unbearable. Administering the " preparation before a shower greatly reduced itching; used after, the itching stopped within 2 minutes.
  • Patient 27 had very difficult eczema over one-third of her body. She treated one arm with a 3-30Kd peat preparation and used the other arm as a control. The treated arm became clear, while the control arm had 25% coverage of eczema.
  • Patient 27 also administered the preparation on her face and it eliminated the pain associated with the eczema on her face less than 15 seconds after application. Steroids were less effective.
  • Patient 28 had mild eczema which could be controlled with steroids using lengthy treatments. Upon application of a 3-30Kd peat preparation, he was free from lesions after 7 days.
  • Patient 29 had a large amount of eczema on her face. After applying a 10-30Kd Peat Preparation twice daily for one week, her face was cleared of all eczema. She continued treatment once daily for another three weeks. The eczema had still not re-emerged after two months.
  • Patient 30 applied a 10-30Kd Peat Preparation to sores from abrasions.
  • One of these sores was infected to the point that it was oozing and weeping.
  • the redness and infection was completely gone and complete healing occurred. This healing occurred as soon, if not sooner, than another untreated sore which did not have any apparent infection.
  • Patient 31 had open and bleeding sores on his hands caused by involuntary scratching of eczema during the night. Cortisone injections controlled the itching for about 4-6 weeks, but the patient was only able to take cortisone shots twice a year. After 2 days of treatment with a 10-30Kd Peat Preparation, the itching stopped and healing began. After 7 days, the eczema was completely controlled. When application of the preparation was discontinued, the eczema returned but to a lesser degree. Following 6 days of renewed treatment, the eczema once again disappeared. Patient 31 continued treatment with the preparation for 8 months with effective control of his eczema. No side effects were observed.
  • Psoriasis - Patients 32 and 33 Patient 32 had suffered from psoriasis on his arms and elbows for over ten years. A 10-30Kd Peat Preparation was applied to one elbow on a twice daily basis for approximately 9 months, with the occasional simultaneous application of fluocinonide cream. Fluocinonide cream alone was used on the other elbow.
  • the elbow treated with the fluocinonide alone evidenced only subsided flaking of the skin, but no decrease in the skin lesions.
  • the patient observed significant improvement within one week by using the preparation combined with the occasional application of fluocinonide cream. Flaking and itching had stopped and the lesions on his skin were reduced in size. Hair started growing in these areas.
  • Patient 32 also applied the preparation to open wounds such as minor cuts and observed good healing effects without infection.
  • Patient 33 had psoriasis that seemed to only manifest itself after a strep throat. Her only successful treatment had been with chemotherapeutic agents. Application of a 10-30Kd Peat Preparation cleared up the treated psoriatic area in 2 to 3 weeks.
  • Epidermal Conditions - Patients 34-44 During the winter months, Patient 34 had an extreme case of dry skin and red rash on the inside of her legs. The itching immediately ceased upon application of the 10-30Kd Peat Preparation. Within one week, the red rash was gone and the dry skin was completely normal. Patient 35 applied a 10-30Kd Peat Preparation to treat sumac poisoning on his legs and arms. He had previously used 1% cortisone treatment to soothe the burning and itching and to clear up the blisters, which took a week to 10 days. The skin would also turn red and peel like a sunburn before the irritation would stop. After applying the preparation, he had immediate relief from the burning and itching. Within 24 hours the blisters were gone, and within 48 hours the redness was gone and the skin looked normal.
  • Patient 36 applied a 10-30Kd Peat Preparation to her lip at the first sign of a cold sore. The preparation stopped the lesion from appearing. There was no pain after the first application.
  • Patient 37 experienced mouth sores from overuse of ibuprofen. A 10-30Kd Peat Preparation was applied directly to the sores and cured the condition in 12 hours. The healing process generally took 3-5 days if untreated. Patient 37 also applied the preparation to numerous cuts and abrasions to effectively avoid infection and accelerate the healing process. Pain was generally controlled within five seconds after application.
  • Patient 38 had boil-like conditions as a result of a lingering staphylococcal infection.
  • the condition generally resulted in an infection that required lancing.
  • Patient 38 also applied the preparation to skin blemishes with excellent healing results.
  • Patient 39 treated a third-degree kitchen stove burn with a 10-30Kd Peat Preparation 10 minutes after the burn was sustained. The associated pain diminished in 15 seconds.
  • Patient 40 applied a 10-30Kd Peat Preparation to her leg about 24 hours after it was burned. At the time she applied the preparation, the burn was quite painful and blistered. Immediately after treatment, the pain subsided. Within 24 hours, the blistering was gone and the burned skin was smooth.
  • Patient 41 Two hours after Patient 41 burned his finger, it was blistered and weeping. After applying a 10-30Kd Peat Preparation, he experienced immediate relief. The blistering was gone overnight. Patient 41 also applied the preparation to finger inflamed by a steel sliver and there was an immediate reduction in pain and pressure.
  • Patient 42 experienced itching in his right eye. After one day, his eye became red and inflamed. Flushing with eye wash did not provide relief. After several days, the eye was completely stuck closed, very swollen and red, and the patient was diagnosed with conjunctivitis. The patient applied a cotton pad soaked with a 10-30Kd Peat Preparation. On the following day, the patient had very little swelling and no pain in his eye, but the eye was still red. He again applied a cotton pad soaked with the preparation before going to bed. On the following day, his eye had no swelling, no pain in the eye and no itching. Two days later, the eye was completely healed.
  • Patient 43 applied a 10-30Kd Peat Preparation to portions of a badly skinned knee. Within two days, all of the soreness and redness was gone and a thin layer scab had formed. The untreated area was still sore to the touch. The scab that formed on the treated area was much thinner than that of the untreated. There was no pus-like substance at any time on the treated area, but there was a continuing secretion of pus for five days on the untreated area. The subject reported that overall healing of the treated wound was at least twice as fast as usual.
  • Patient 44 had acne congolbata on his back, buttocks, and legs. This is a severe, painful condition of boils which must be frequently lanced. He was being treated with Prednisone at a dose of 27 g a day. This treatment barely contained the boils. The patient was visiting the Emergency Room at the hospital as much as once a week for lancing. He began using 60 mgs/250 ml peat preparation #44 in a cream. He was able to reduce the dose of Prednisone to 5 mg a day, with continued reduction of the Prednisone dose thereafter. With continuing treatment, the boils stopped erupting and the pain was diminished.
  • Shingles - Patient 46 Two children were diagnosed with shingles. A prescribed medication was used on them for three weeks with no relief. Peat preparation #44 was administered topically and provided immediate relief form the pain. In two days, the lesions were gone.
  • Example 6 Mixtures and Complexes Inorganic composition mixtures and/or composed of complexes of the present invention were also synthesized and administered to human patients. Inorganic mixtures were prepared using a combination of gypsum (CaS0 4 *2H 2 0) and potassium sulfate (K 2 S0 4 ) . More specifically, a "Mixture" containing 0.6 mg of equimolar CaS0 4 *2H 2 0 and K 2 S0 4 in a carrier comprising 2ml of ethanamine-N-N-diethyl- trifluoroacetate (EDT) and glycerol in a 1:1 ratio was formulated.
  • gypsum CaS0 4 *2H 2 0
  • K 2 S0 4 potassium sulfate
  • Patient 49 applied the Mixture topically to treat long-term low back pain due to nerve damage caused by disc deterioration. Pain relief occurred within seconds and was sustained.
  • Example 7 Synthesis of Syngenite Syngenite was synthesized according to the following protocol.
  • Solution A was formulated by dissolving 125 mmoles of K J SO ⁇ J in distilled water (450 ml) at room temperature.
  • Solution B was formulated by mixing 2.5 mmoles CaS0 4 in distilled water (50 ml) at room temperature with constant stirring.
  • Solution A was slowly poured into solution B with constant stirring. The reaction mixture was maintained for 4 hr at an isotherm of 38°C.
  • Example 8 Comparative Studies Experiments were conducted to compare the effectiveness of samples #44 and #46 to peak #11. Based upon the reports of the test subject, samples #44 and #46 both worked about 30% as well as peak #11. When samples #44 and #46 were administered in an EDT carrier, however, each sample produced results that were comparable to those obtained with peak #11.
  • Another patient topically administered three different preparations to an area of pain.
  • the three preparations included: (1) a 3-30Kd peat preparation; (2) a peak #11 preparation in a cream; and (3) an equi olar mixture of CaS0 4 -2H 2 ⁇ and K 2 S0 4 (each about 0.03% by weight) in 1,2,3- trihydroxypropanol.
  • the preparations were applied to different areas to reduce intense pain associated with a chronic arthritic condition of many years' duration.
  • the patient reported that the 3-30Kd peat preparation produced noticeable but short-lived relief for 20 minutes, with some relief lasting for approximately one hour.
  • the patient furthermore reported that the use of the mixture in the 1,2,3-trihydroxypropanol carrier produced relief equivalent to the peak #11, and had the additional advantage that it was neither greasy nor sticky.
  • Sample #1 provides clear analgesic benefit for all subjects compared to the other samples.
  • the composition of sample #1 was 0.25% CaS0 4 -2H 2 0 plus 0.5% syngenite in UNIBASE cream.
  • U ⁇ IBASE is a commercially available topical cream.
  • In the subject with pain due to neuritis there was also a very significant level of local inflammation which was virtually completely ameliorated by the application of sample #1.
  • This example demonstrates several important aspects of the invention.
  • the inorganic compositions of the present invention also demonstrate significant utility for veterinary applications.
  • Animal subject A was a dog that started intensive scratching after a visit to the seashore. After two to five days, itching increased with some hair loss as a result of continued scratching. On day six, the dog was sprayed with flea and tick powder but showed no improvement. The bites continued to worsen and soon secreted a pus-like substance.
  • the dog was treated by applying a 10-30Kd Peat Preparation in spray form. The spray was re-applied 8 hours later. On the following day, there was no pus and less scratching. The preparation was reapplied three times during the day and the bites were smaller and less red. After one more day of treatment, the bites were smaller in size, only pink in color and there was no scratching.
  • Animal subject B was a race horse suffering from sores on its legs.
  • the horse was diagnosed as being allergic to mud and was treated with triamcinolone 0.1% acetonide cream. He had scabbing and oozing of pus on his legs and was sore and stiff. There was no improvement after four months of treatment under veterinary supervision.
  • a 10-30Kd Peat Preparation was sprayed directly on the horse's legs once a day. After three days, healing was noted. After one week, the infected areas were healed and the horse's hair was growing back.
  • Animal subject C was a large dog that had serious eczema and dry skin since birth. Numerous sprays, powders, shampoos, pills and injections were administered without success. After spraying the dog with a 10-30Kd Peat Preparation for two weeks, itching was resolved and there was less flaking and dry skin.
  • Animal subject F a German Short Hair dog, was treated with the 10-30Kd Peat Preparation for a non-flea associated, non-specific dermatitis. Applications were inconsistent and usually twice daily. There was a noticeable reduction in the scratching and dermatitis within one week.
  • Bovine ocular squamous cell carcinoma of cattle is a common neoplasm of the bovine eye and adenexa. Squamous cell carcinomas may also affect other species of animals. Bovine ocular squamous cell carcinoma is best known by its colloquial name of Cancer-eye.
  • the initial lesion may be on the eyelid or any structure in the conjunctival sac except the vascular cornea or the pigmented eyelid.
  • the lesion develops through three stages. The first stage is the formation of a plaque; the second stage is formation of a papilloma; and the third stage is the squamous cell carcinoma.
  • the first two stages are non-malignant and have up to an 88% regression rate.
  • the third stage is malignant and does not regress.
  • carcinomas develop most commonly on the nictating membrane, the eyelids, and the corneal limbus. They grow rapidly and are actively invasive, often metastasizing to the lymph nodes.
  • the above-described cancer most usually affects Hereford cattle, but has been found in Ayrshire, Simmental, Shorthorn, Holstein and cross-bred animals thereof.
  • Several cattle were successfully treated with a 10-30Kd Peat Preparation.
  • a cow having bovine ocular squamous cell carcinoma was treated by injecting 5 ml of a solution containing 3 mg/ml 10-30Kd Peat Preparation into the sarcoma. Ten days later the tissue firmed up, blood supply increased and the tumor had shrunk considerably.
  • Another cow had a squamous cell carcinoma lesion .5 cm 2 on its corneal limbus. The growth was surgically removed, and then 0.5 ml of 10-30Kd Peat Preparation was injected into area. No further treatment was administered for one year, when a small plaque was removed.

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  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Inorganic Chemistry (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Des compositions inorganiques, comprenant un mélange et/ou un complexe de substances contenant du calcium et du sulfate, permettent de traiter des maladies, blessures et troubles divers, y compris des blessures à soigner, des douleurs, démangeaisons, inflammations, proliférations cellulaires anormales ou infections fongiques, bactériennes, virales ou dues à des rickettsies, et d'autres affections similaires. On peut tirer ces compositions inorganiques de la tourbe et de substances apparentées ou les produire par synthèse.
PCT/US1993/010489 1992-10-29 1993-10-28 Melanges ou complexes contenant du calcium et du sulfate WO1994009798A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU55895/94A AU5589594A (en) 1992-10-29 1993-10-28 Mixtures or complexes containing calcium and sulfate
EP94901234A EP0666750A1 (fr) 1992-10-29 1993-10-28 Melanges ou complexes contenant du calcium et du sulfate
JP6511380A JPH08502976A (ja) 1992-10-29 1993-10-28 カルシウムおよび硫酸塩を含有した組成物および複合体、その合成法、これを用いた治療法、これを含んでなる化粧用調製物

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US96979392A 1992-10-29 1992-10-29
US07/969,793 1992-10-29

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WO1994009798A1 true WO1994009798A1 (fr) 1994-05-11

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JP (1) JPH08502976A (fr)
AU (1) AU5589594A (fr)
CA (1) CA2148256A1 (fr)
WO (1) WO1994009798A1 (fr)

Cited By (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2081771A1 (es) * 1994-08-05 1996-03-01 Arredondo Javier Olaechea Composicion de un producto liquido de uso topico para quemaduras y golpes.
FR2725901A1 (fr) * 1994-10-25 1996-04-26 Thorel Jean Noel Utilisation du calcium en cosmetologie dans le traitement local des phenomenes irritatifs
FR2726187A1 (fr) * 1994-10-26 1996-05-03 Jean Noel Thorel Utilisation du calcium par voie topique dans le traitement local des dermatoses hyperproliferatives comme le psoriasis
FR2732602A1 (fr) * 1995-04-10 1996-10-11 Oreal Utilisation d'un sel d'un metal alcalino-terreux dans une composition cosmetique ou pharmaceutique pour traiter les prurits
FR2732600A1 (fr) * 1995-04-10 1996-10-11 Oreal Utilisation d'un sel d'un metal alcalino-terreux dans une composition cosmetique et/ou dermatologique et composition obtenue
WO1996037207A2 (fr) * 1995-05-25 1996-11-28 Biofrontiers, Inc. Compositions pharmaceutiques contenant du sulfate de calcium
EP0801570A1 (fr) * 1994-12-21 1997-10-22 Cosmederm Technologies Formulations et procedes pour diminuer l'irritation de la peau
US5683725A (en) * 1995-05-25 1997-11-04 Biofrontiers, Inc. Modulation of substance P by compounds containing calcium sulfate and methods relating thereto
US5851556A (en) * 1995-04-10 1998-12-22 Societe L'oreal S.A. Use of a salt of an alkaline-earth metal as TNF-A or substance P inhibitor in a topical composition and composition obtained
US5866168A (en) * 1995-10-26 1999-02-02 Societe L'oreal S.A. Dermatological/pharmaceutical compositions comprising lanthanide, manganese, tin, zinc, yttrium, cobalt, barium and/or strontium salts as substance P antagonists
US5900257A (en) * 1995-10-26 1999-05-04 Societe L'oreal S.A. Cosmetic/pharmaceutical compositions comprising lanthanide manganese, tin and/or yttrium salts as substance P antagonists
WO2000048477A2 (fr) * 1999-02-19 2000-08-24 Morningstar Diagnostics, Inc. Solution acide de complexes du groupe iia moderement solubles
WO2000056157A1 (fr) * 1999-03-22 2000-09-28 H.P.T. Research, Inc. Agent desinfectant
EP1129715A1 (fr) * 2000-02-25 2001-09-05 Werner Dr. Reichen Utilisation de magnésium, de calcium et de silicium comme curatif des différentes maladies et pour le bien-être général
DE10025622A1 (de) * 2000-05-24 2001-11-29 Staatsbad Meinberg Gmbh Verfahren zur Herstellung eines kosmetischen Mittels aus Moorextrakt und Verfahren zur Herstellung des Moorextraktes
US6627229B2 (en) * 2000-02-18 2003-09-30 Hiromi Houzawa Antiviral agent and method of producing the same
US6902753B1 (en) 1999-02-19 2005-06-07 Mionix Corporation Acidic solution of sparingly-soluble group IIA complexes
US6926912B1 (en) 1997-09-19 2005-08-09 Ineos Silicas Limited Metal compounds, mixed or sulphated, as phosphate binders
EP1576880A1 (fr) * 2004-03-16 2005-09-21 Well-being Biochemical Corp. Composition antibactérienne, antivirale et antifongique, sa préparation et utilisation
US7087219B2 (en) * 2003-05-28 2006-08-08 Stanislaw R. Burzynski Toothpaste containing anticancer agents
US7241460B2 (en) 2001-09-28 2007-07-10 Santosolve As Strontium compound for treatment of sub-dermal soft tissue pain
WO2007085681A1 (fr) * 2006-01-24 2007-08-02 Medgenerics Oy Substance thérapeutique contenant des sels de magnésium pour le traitement de tumeurs ou similaires, et utilisation de sels de magnésium
US7323436B2 (en) 1999-02-19 2008-01-29 Mionix Corporation Adduct having an acidic solution of sparingly-soluble group IIA complexes
GB2441499A (en) * 2006-09-08 2008-03-12 Jasin El Sammadoni A slimming spray
US7387799B2 (en) 2003-05-19 2008-06-17 Well-Being Biochemical Corp. Anti-bacterial, anti-viral, and anti-fungus composition, its preparation and use
US7858124B2 (en) 2003-07-29 2010-12-28 Well-Being Biochemical Corp. Anti-bacterial, anti-virus, and anti-fungus composition, its preparation and use
US8147855B2 (en) 1994-12-21 2012-04-03 Cosmederm Bioscience, Inc. Methods for inhibiting sensory responses in the skin such as pain and itch using topical product formulations containing strontium
US9066917B2 (en) 2009-08-03 2015-06-30 Cytochroma Development Inc. Mixed metal compound
US9168270B2 (en) 2006-01-31 2015-10-27 Opko Ireland Global Holdings, Ltd. Water-insoluble, iron-containing mixed metal, granular material
US9566302B2 (en) 2010-02-04 2017-02-14 Opko Ireland Global Holdings, Ltd. Composition comprising mixed metal compounds and xanthan gum
US10155040B2 (en) 2007-10-16 2018-12-18 Opko Ireland Global Holdings, Ltd. Mixed metal compounds for treatment of hyperphosphataemia
US10201501B2 (en) 2007-07-27 2019-02-12 Opko Ireland Global Holdings, Ltd. Mixed metal compounds used as antacids

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EP0217975A1 (fr) * 1985-10-08 1987-04-15 Psori-Med Ag Mélange de sels pour le traitement du psoriasis et autres maladies de la peau
US4735802A (en) * 1986-05-05 1988-04-05 Le Bich N Topical dermatological composition and method of treatment
WO1991011168A1 (fr) * 1988-10-31 1991-08-08 United States Gypsum Company Composition d'hygiene dentaire pour reduire les parodontoses
WO1992016216A1 (fr) * 1991-03-16 1992-10-01 Torf Establishment Produits bioactifs derives de la tourbe, compositions pharmaceutiques et cosmetiques les contenant

Patent Citations (4)

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Publication number Priority date Publication date Assignee Title
EP0217975A1 (fr) * 1985-10-08 1987-04-15 Psori-Med Ag Mélange de sels pour le traitement du psoriasis et autres maladies de la peau
US4735802A (en) * 1986-05-05 1988-04-05 Le Bich N Topical dermatological composition and method of treatment
WO1991011168A1 (fr) * 1988-10-31 1991-08-08 United States Gypsum Company Composition d'hygiene dentaire pour reduire les parodontoses
WO1992016216A1 (fr) * 1991-03-16 1992-10-01 Torf Establishment Produits bioactifs derives de la tourbe, compositions pharmaceutiques et cosmetiques les contenant

Cited By (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2081771A1 (es) * 1994-08-05 1996-03-01 Arredondo Javier Olaechea Composicion de un producto liquido de uso topico para quemaduras y golpes.
FR2725901A1 (fr) * 1994-10-25 1996-04-26 Thorel Jean Noel Utilisation du calcium en cosmetologie dans le traitement local des phenomenes irritatifs
FR2726187A1 (fr) * 1994-10-26 1996-05-03 Jean Noel Thorel Utilisation du calcium par voie topique dans le traitement local des dermatoses hyperproliferatives comme le psoriasis
EP0801570A1 (fr) * 1994-12-21 1997-10-22 Cosmederm Technologies Formulations et procedes pour diminuer l'irritation de la peau
US8449923B2 (en) 1994-12-21 2013-05-28 Cosmederm Bioscience, Inc. Methods for inhibiting sensory nerves by topically administering strontium-containing compositions to keratinized skin
EP0801570A4 (fr) * 1994-12-21 1998-12-30 Cosmederm Technologies Formulations et procedes pour diminuer l'irritation de la peau
US8147855B2 (en) 1994-12-21 2012-04-03 Cosmederm Bioscience, Inc. Methods for inhibiting sensory responses in the skin such as pain and itch using topical product formulations containing strontium
US5851556A (en) * 1995-04-10 1998-12-22 Societe L'oreal S.A. Use of a salt of an alkaline-earth metal as TNF-A or substance P inhibitor in a topical composition and composition obtained
FR2732600A1 (fr) * 1995-04-10 1996-10-11 Oreal Utilisation d'un sel d'un metal alcalino-terreux dans une composition cosmetique et/ou dermatologique et composition obtenue
FR2732602A1 (fr) * 1995-04-10 1996-10-11 Oreal Utilisation d'un sel d'un metal alcalino-terreux dans une composition cosmetique ou pharmaceutique pour traiter les prurits
US5683725A (en) * 1995-05-25 1997-11-04 Biofrontiers, Inc. Modulation of substance P by compounds containing calcium sulfate and methods relating thereto
WO1996037207A3 (fr) * 1995-05-25 1997-02-27 Biofrontiers Inc Compositions pharmaceutiques contenant du sulfate de calcium
WO1996037207A2 (fr) * 1995-05-25 1996-11-28 Biofrontiers, Inc. Compositions pharmaceutiques contenant du sulfate de calcium
US5866168A (en) * 1995-10-26 1999-02-02 Societe L'oreal S.A. Dermatological/pharmaceutical compositions comprising lanthanide, manganese, tin, zinc, yttrium, cobalt, barium and/or strontium salts as substance P antagonists
US5900257A (en) * 1995-10-26 1999-05-04 Societe L'oreal S.A. Cosmetic/pharmaceutical compositions comprising lanthanide manganese, tin and/or yttrium salts as substance P antagonists
US8568792B2 (en) 1997-09-19 2013-10-29 Cytochroma Development Inc. Metal compounds, mixed or sulphated, as phosphate binders
US7799351B2 (en) 1997-09-19 2010-09-21 Ineos Healthcare Limited Metal compounds, mixed or sulphated, as phosphate binders
US6926912B1 (en) 1997-09-19 2005-08-09 Ineos Silicas Limited Metal compounds, mixed or sulphated, as phosphate binders
US9242869B2 (en) 1997-09-19 2016-01-26 Opko Ireland Global Holdings, Ltd. Metal compounds mixed or sulphated, as phosphate binders
WO2000048477A3 (fr) * 1999-02-19 2000-11-30 Morningstar Diagnostics Inc Solution acide de complexes du groupe iia moderement solubles
AU774058B2 (en) * 1999-02-19 2004-06-17 Mionix Corporation Acidic solution of sparingly-soluble group IIA complexes
US6902753B1 (en) 1999-02-19 2005-06-07 Mionix Corporation Acidic solution of sparingly-soluble group IIA complexes
WO2000048477A2 (fr) * 1999-02-19 2000-08-24 Morningstar Diagnostics, Inc. Solution acide de complexes du groupe iia moderement solubles
US7323436B2 (en) 1999-02-19 2008-01-29 Mionix Corporation Adduct having an acidic solution of sparingly-soluble group IIA complexes
WO2000056157A1 (fr) * 1999-03-22 2000-09-28 H.P.T. Research, Inc. Agent desinfectant
US6627229B2 (en) * 2000-02-18 2003-09-30 Hiromi Houzawa Antiviral agent and method of producing the same
EP1129715A1 (fr) * 2000-02-25 2001-09-05 Werner Dr. Reichen Utilisation de magnésium, de calcium et de silicium comme curatif des différentes maladies et pour le bien-être général
DE10025622A1 (de) * 2000-05-24 2001-11-29 Staatsbad Meinberg Gmbh Verfahren zur Herstellung eines kosmetischen Mittels aus Moorextrakt und Verfahren zur Herstellung des Moorextraktes
US7241460B2 (en) 2001-09-28 2007-07-10 Santosolve As Strontium compound for treatment of sub-dermal soft tissue pain
US9050312B2 (en) 2001-09-28 2015-06-09 Santosolve As Strontium compound for treatment of sub-dermal soft tissue pain
US7387799B2 (en) 2003-05-19 2008-06-17 Well-Being Biochemical Corp. Anti-bacterial, anti-viral, and anti-fungus composition, its preparation and use
US7976876B2 (en) 2003-05-19 2011-07-12 Well-Being Biochemical Corp. Anti-bacterial, anti-virus, and anti-fungus composition, its preparation and use
US7087219B2 (en) * 2003-05-28 2006-08-08 Stanislaw R. Burzynski Toothpaste containing anticancer agents
US7858124B2 (en) 2003-07-29 2010-12-28 Well-Being Biochemical Corp. Anti-bacterial, anti-virus, and anti-fungus composition, its preparation and use
EP1576880A1 (fr) * 2004-03-16 2005-09-21 Well-being Biochemical Corp. Composition antibactérienne, antivirale et antifongique, sa préparation et utilisation
WO2007085681A1 (fr) * 2006-01-24 2007-08-02 Medgenerics Oy Substance thérapeutique contenant des sels de magnésium pour le traitement de tumeurs ou similaires, et utilisation de sels de magnésium
US9168270B2 (en) 2006-01-31 2015-10-27 Opko Ireland Global Holdings, Ltd. Water-insoluble, iron-containing mixed metal, granular material
US9907816B2 (en) 2006-01-31 2018-03-06 Opko Ireland Global Holdings, Ltd. Water-insoluble, iron-containing mixed metal, granular material
GB2441499B (en) * 2006-09-08 2011-09-14 Jasin El Sammadoni Slimming Spray
GB2441499A (en) * 2006-09-08 2008-03-12 Jasin El Sammadoni A slimming spray
US10201501B2 (en) 2007-07-27 2019-02-12 Opko Ireland Global Holdings, Ltd. Mixed metal compounds used as antacids
US10155040B2 (en) 2007-10-16 2018-12-18 Opko Ireland Global Holdings, Ltd. Mixed metal compounds for treatment of hyperphosphataemia
US9066917B2 (en) 2009-08-03 2015-06-30 Cytochroma Development Inc. Mixed metal compound
US9314481B2 (en) 2009-08-03 2016-04-19 Opko Ireland Global Holdings, Ltd. Method
US9566302B2 (en) 2010-02-04 2017-02-14 Opko Ireland Global Holdings, Ltd. Composition comprising mixed metal compounds and xanthan gum

Also Published As

Publication number Publication date
AU5589594A (en) 1994-05-24
EP0666750A1 (fr) 1995-08-16
CA2148256A1 (fr) 1994-05-11
JPH08502976A (ja) 1996-04-02

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