[go: up one dir, main page]

WO2012032364A1 - Solution stabilisée d'acide ortho-silicique à base d'acide salicylique comme inhibiteur efficace de sa polymérisation, sa préparation et son utilisation - Google Patents

Solution stabilisée d'acide ortho-silicique à base d'acide salicylique comme inhibiteur efficace de sa polymérisation, sa préparation et son utilisation Download PDF

Info

Publication number
WO2012032364A1
WO2012032364A1 PCT/HR2011/000034 HR2011000034W WO2012032364A1 WO 2012032364 A1 WO2012032364 A1 WO 2012032364A1 HR 2011000034 W HR2011000034 W HR 2011000034W WO 2012032364 A1 WO2012032364 A1 WO 2012032364A1
Authority
WO
WIPO (PCT)
Prior art keywords
silicic acid
acid
ortho
silicon
solution
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/HR2011/000034
Other languages
English (en)
Inventor
Ivica Cepanec
Antonio Lelas
Marijan Ramljak
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Creogen d o o
Original Assignee
Creogen d o o
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Creogen d o o filed Critical Creogen d o o
Publication of WO2012032364A1 publication Critical patent/WO2012032364A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/25—Silicon; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/368—Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
    • C01B33/00—Silicon; Compounds thereof
    • C01B33/113—Silicon oxides; Hydrates thereof
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
    • C01B33/00—Silicon; Compounds thereof
    • C01B33/20—Silicates
    • C01B33/32—Alkali metal silicates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/10—General cosmetic use

Definitions

  • the present invention relates to the composition of highly bioavailable silicon (Si) which is used in medicine, cosmetics, veterine and agronomy.
  • the present invention solves technical problem of effective stabilization of ortho-silicic acid (H Si0 4 ) , which is used as nutritional and therapeutic source of highly bioavailable silicon
  • Formulation of the product is in the form of a solution comprising:
  • diluent selected from the group consisting of: purified water, 1, 2-propylene glycol, glycerol, ethanol, or their mixtures, in amounts of up to 100% w/w of the formulation.
  • Silicon (Si) is important biogenic microelement which exhibits several important roles in human and animal organism:
  • Jugdaohsingh Orthosilicic acid stimulates collagen type I synthesis and osteoblast-like cells in vitro, Bone 32 (2003) 127; S. Spripanyakorn, R. Jungdaohsingh, R. P. H. Thompson, J. J. Powell: Dietary silicon and bone health, Nutr. Bull. 30 (2005) 222];
  • (v) exhibits antiinflammatory effect; e.g. helps at various inflammatory diseases like rheumatoid arthritis, muscle inflammation, skin disorders such as psoriasis, seborrheic dermatitis, neurodermitis, skin irritations, accelerates wound healing, soothes decubitus and other skin disorderds and diseases
  • silicic acid in its monomeric form, ortho-form (H 4 Si0 4 ) is not stable and at higher concentration, but undergoes polymerization with formation of dimer (H 6 Si 2 0 7 ) , trimer (H 8 Si 3 O 10 ) , and linear chain oligomers (SI) which are still water soluble.
  • Linear chain polymers of silicic acid (SI) undergo further polymerization yielding tridimensional, branched polymers (S2) which are not of significant water solubility but form opalescent gel.
  • the polymerization process proceeds further with formation of hydratized silicon dioxide (silica gel; Si0 2 'xH 2 0) .
  • Branched polymers of silicic acid are not biologically available [H. Yokoi, S. Enomoto: Effect of degree of polymerization of silicic acid on the gastrointestinal absorption of silicate in rats, Chem. Pharm. Bull. 27 (1979) 1733; K. Van Dyck, R. Van Cauwenbergh, H. Robberecht: Bioavailability of silicon from food and food supplements, Fresenius J. Anal. Chem. 363 (1999) 541].
  • silicic acid For application in pharmacy, cosmetics, and veterinary, only pharmaceutically acceptable forms of silicic acid can be employed. For use in agriculture, also, only non-toxic forms of silicic acid of high bioavailability can be applied.
  • humectants like polyethylene glycol, polysorbates, plant gums, substituted cellulose, 1 , 2-propylene glycol, pectin, ethoxylated derivatives of higher fatty acids, acetylated or hydroxypropyl-derivatized starch, starch phosphate, urea, sorbitol, maltitol, vitamins [W. A. Kros, U.S.
  • Beside choline chloride-stabilized silicic acid on the market exist various food supplements which contain silicon in the forms of amorphous or colloidal silicon dioxide (Si0 2 ) .
  • Si0 2 amorphous or colloidal silicon dioxide
  • such products are characterized by very low bioavailability [R. Jugdaohsingh : Silicon and bone health, J. Nutr. Health Aging 11 (2007) 99] .
  • Somewhat effective (bioavailable) sources of silicic acid are also various plant drugs like extracts of horsetail (Equisetum arvense) , nettle (Urtica dioica) , and some other plants.
  • portions of soluble (and thus bioavailable) silicic acid from these healing plants usually do not exceed 1/10 of total amounts. All remained silicic acid is not soluble and, as such, not bioavailable [D. Kustrak: Pharmacognosy and phytopharmacy (in Wegn) Golden marketing-Tehnicka knjiga, Zagreb, Croatia (2005)].
  • silicon based products are used for only a few years. They are used for increasing resistance of plants to stress (at drought or hail) and against fungal diseases. It seems that they also pasively protect from insect attacks by forming thin hard barrier of silicon dioxide on the plant leaves.
  • the most known product are those based on horsetail ⁇ Equisetum arvense) extract or finelly milled quartz sand (silicon dioxide; Si0 2 ) in organic, and solution of potassium silicate (30% K 2 Si0 3 ) in conventional agriculture (mainly at grape; e.g. perennialSil-Matrix" ) . These products are usually applied by foliar spraying.
  • Salicylic acid (1) is a well known pharmaceutically active substance which, as such, or in forms of its derivatives (e.g. salicylamide, acetylsalicylic acid) , is widely used as antiinflammatoric, analgesic, and antipyretic for decades.
  • salicylamide, acetylsalicylic acid e.g. acetylsalicylic acid
  • keratolytic removes dead top skin layers
  • cosmetic peeling
  • keratoplastic acts as keratoplastic . Beside this, exhibits topical microbiocidal action.
  • the present invention represents improved pharmaceutical, cosmetic, veterinary or agrochemical composition which is effective source of highly bioavailable silicon.
  • the formulation is consisting of:
  • diluent selected from the group consisting of: purified water, 1 , 2-propylene glycol, glycerol, ethanol, or their mixtures, in amounts of up to 100% w/w of the formulation.
  • the following pharmaceutically acceptable acids can be used: hydrochloric (HC1) , sulfuric (H 2 S0 4 ) , nitric (HN0 3 ) , phosphoric (H 3 P0 4 ) , methanesulfonic (CH 3 SO 3 H) , benzenesulfonic (C 6 H 5 S0 3 H) , salicylic ( 1 , 2-C 6 H 4 (OH) COOH) or sulfosalicylic [C 6 H 3 (3- COOH) (4-OH)S0 3 H] acid, mixtures of these acids, or other acids which are not of significant toxicity for human, animal, or plant organism.
  • salicylic acid as pharmaceutically acceptable acid represents the special case of the present invention, because then it is in the same time:
  • Pharmaceutically acceptable base is selected from the group comprising sodium hydroxide (NaOH) , potassium hydroxide (KOH) , ammonium hydroxide (NH OH) , tetramethylammonium hydroxide [N(CH 3 ) 4 OH], tetraethylammonium hydroxide [N (C 2 H 5 ) 4 OH] , mixtures of these bases, or other bases characterized by:
  • salicylic acid (1) acts as effective stabilizer of ortho-silicic acid (H Si0 ) at pH values closed to neutral. In this manner, it inhibits its polymerization into biologically unavailable polymers of silicic acid. Consequently increases its bioavailability after oral administration of the formulation from the present invention.
  • TEOS tetraethyl orthosilicate
  • Samples are prepared by addition of 0.0054 mol of choline chloride (0.75 g) or L-serine (0.57 g) in hydrolyzed solution of sodium silicate (6.00 g distilled water + 0.44 g NaOH + 1.2 mL TEOS), with subsequent dilution with distilled water up to the total weight of 15.00 g [contains 150 mg (1% w/w) of Si].
  • the solution of the complex was prepared by addition of salicylic acid (0.75 g; 0.0054 mol) in previously prepared solution of sodium silicate (6.00 g distilled water + 0.44 g NaOH + 1.2 mL TEOS), with subsequent dilution with distilled water up to the total weight of 15.00 g [contains 150 mg (1% w/w) of Si].
  • Solutions are prepared by mixing previously prepared solution of sodium silicate (6.00 g distilled water + 0.44 g NaOH + 1.2 mL TEOS) and 2.25 g (15% w/w) or 6.00 g (40% w/w) of 1 , 2-propylene glycol with subsequent dilution with distilled water, up to the total weight of 15.00 g [contains 150 mg (1% w/w) of Si].
  • the solution of the complex was prepared by addition of salicylic acid (0.75 g; 0.0054 mol) to previously prepared solution of sodium silicate (6.00 g distilled water + 0.44 g NaOH + 1.2 mL TEOS) . Reaction mixture was stirred at room temperature during 1 h. Then, 1, 2-propilene glycol (2.25 g; 15% w/w) was added, and subsequently diluted with distilled water, up to the total weight of 15.00 g [contains 150 mg (1% w/w) of Si] .
  • Solutions like those of the complex 2 are clear and colourless solutions, stable to the occurence of gelling at room temperature (17-25 °C) , and at temperatures ⁇ 30 °C, during minimally 2 years.
  • the formulation from the present invention can be prepared as complex with ortho-silicic acid (HSi0 4 ) with salicylic acid salts (like disodium salicylate) in molar ratio of 1:2.
  • ortho-silicic acid HSi0 4
  • salicylic acid salts like disodium salicylate
  • the formulation from the present invention can be prepared as stabilized solution of ortho- silicic acid (H 4 Si0 4 ) also in acidic medium, by the influence of one or more above-mentioned pharmaceutically acceptable acid (0.1-4 molar equivalents) in the presence of 1-2 molar equivalents of salicylic acid, calculated to H 4 Si0 .
  • cCloudRelative stability is expressed as numerical parameter, coefficient, which describes stability of ortho-silicic acid in the given sample in comparison with the standard [pure solution of silicic acid (HSi0 4 ) ] . It shows stabilizing or destabilizing effect on ortho-silicic acid, in other words on its polymerization (gelling) .
  • Samples are prepared by addition of 0.0054 mol of choline chloride (0.75 g) or L-serine (0.57 g) to a solution of ortho-silicic acid (H 4 Si0 4 ; 10.00 g destilirana voda + 1.2 mL TEOS + 0.2 mL 85% H 3 P0 4 ; 3 h-stirring / room temperature) with subsequent dilution with distilled water, up to the total weight of 15.00 g [contains 150 mg (1% w/w) of Si] .
  • ortho-silicic acid H 4 Si0 4 ; 10.00 g destilirana voda + 1.2 mL TEOS + 0.2 mL 85% H 3 P0 4 ; 3 h-stirring / room temperature
  • Samples are prepared by addition of salicylic acid (0.75 g; 0.0054 mol) to a solution of tetraethyl orthosilicate (TEOS; 1.2 mL; 1.12 g; 0.0054 mol) in 1 , 2-propylene glycol (10.00 g) .
  • Distilled water (0.4 mL; 0.022 mol; 4.1 mol. equiv.) was added to the reaction mixture, and stirred at room temperature during 5 h. Then, 1,2- propylene glycol was added to the solution up to the total weight of 15.00 g [contains 150 mg (1% w/w) of Si].
  • amino acid serine which is also described in the literature as stabilizer of ortho-silicic acid, does exhibit slight stabilizing effect, indeed. However, this effect is almost negliable because observed increase of gelling time was only 8-10% prolonged against that for the standard (Experiments 3; Tables 2 and 3) .
  • salicylic acid (1) exhibits significant effect of stabilization of ortho-silicic acid (H 4 Si0 4 ) where observed polymerization time was 2.2x longer (Experiments 4; Tables 2 and 3), what suggest on high stability of the complex H 4 Si0 4 -salicylic acid (compound 3) .
  • humectant can be also used glycerol.
  • alternative diluent beside purified water, can be employed ethanol, or mixtures of these substances.
  • Solutions of the complex like compound 3 are also clear, colourless and relatively viscous solutions, stable to occurrence of gelling at room temperature (17-25 °C) , and at temperatures ⁇ 30 °C, during minimally 2 years.
  • formulation of the present invention provides all known positive therapeutic effects of silicic acid on human, animal or plant organism, which are known to those skilled in the art.
  • the present formulation is used in the following medicinal, cosmetic, and veterinary indications:
  • (ii) takes part in structure of arterial, vein, and capillary walls, increases elasticity and hardness of blood vessels, decreases its permeability; also takes part in structure of connective tissue and formation of functional tertiary structure of building proteins of soft organs like liver, lung, and brain;
  • antiinflammatory effect of silicon and silicic acid therapy of various acute and chronic inflammatory diseases, e.g. positively acts at various inflammations of locomotive system such as muscle inflammations, rheumatoid arthritis, etc; skin diseases like psoriasis, seborrheic dermatitis, neurodermitis, eczema, skin irritations, burns, wound healing, at dandruff, and at other skin disorders and diseases; also positively acts at other inflammatory diseases;
  • (v) acts as cross-linking agent for glucosaminoglycans and mucopolysaccharides, and thus helps function of joints, ligaments, and production of synovial fluid; (vi) inhibits resorption of aluminum (Al 3+ ) from gastrointestinal tract, thus preventively acts on development of neurodegenerative diseases like Alzheimer or Parkinson diseases ;
  • the formulation from the present invention is used as adjuvant in treatment of pain and decreasing of increased body temperature. This is expecially recommended at indications where basic patological condition is consequence of silicon deficiency.
  • the formulation of the present invention due to the content of salicylic acid, shows:
  • microbiocidal effect (iii) microbiocidal effect.
  • the latter effects of salicylic acid are excellently supplemented with basic actions of silicon, where effects of refreshing of the skin are achieved through combination of wrinkle reducing (biosynthesis of collagen and elastin) , keratolytic/keratoplastic, and microbiocidal effects.
  • the formulation from the present invention at topical application provides positive effects in conditions like:
  • the formulation of the present invention provides:
  • the formulation of the present invention intended for medicinal, cosmetic, veterinary, and agrochemical applications is in the dosing form of solution (concentrate) .
  • the solution is diluted with water and administered orally in a dosage which corresponds to the following daily intakes of silicon (Si) :
  • the present formulation is also diluted with water up to the final concentration od silicon from 0.005-0.1% w/w, and applied by foliar application by using all common spraying equipments .
  • the formulation of the present invention can be used as starting material (intermediate) for production of other pharmaceutical products, cosmetics, then veterinary or agrochemical products with content of silicon (Si) of high bioavailability.
  • Basic complexes of ortho-silicic (H 4 Si0 4 ) and salicylic acid are prepared by hydrolysis of precursor of silicic acid ( PSA) tetraethyl orthosilicate (TEOS) :
  • PSA PSA
  • Acidic complexes of salicylic and ortho-silicic acid such as compound 3 are prepared by addition of 0.1-4 molar equivalents of pharmaceutically acceptable acid into previously prepared solution of precursor of silicic acid ( PSA) and salicylic acid in the diluent .
  • diluent or solvent 1 2-propylene glycol, purified water, glycerol, ethanol, or mixtures of these substances can be employed.
  • Reactions are conducted by vigorous stirring at temperatures from - 10 °C to +40 °C, preferably from +15 °C to +30 °C (conditions of room temperature) during 0,5-6 h.
  • TEOS tetraethyl orthosilicate
  • SiCl 4 tetraethyl orthosilicate
  • available commercial products are of very high purity due to the fact that TEOS is readily purified by distillation.
  • final product of very high purity with the content of unwanted heavy metals (Pb, Cd, Hg, As) far under common limits for pharmaceutical products and food supplements can be produced.
  • sodium or potassium silicate are difficult to purify from heavy metals, so, commercial products are not of so high level of chemical purity.
  • ortho-silicic acid (HSi0 ) in status nascendi generated in the reaction, forms the complex with:
  • the formulation of the present invention is clear, colourless, more or less viscous solution.
  • TEOS tetraethyl orthosilicate
  • Si silicon
  • paked into plastic bottles four molar equivalents of ethanol (C 2 H 5 OH) are generated. Since ethanol in this concentration is completely harmless and does not influence negatively on the stability of the present solution, it is not removed but kept in the final product as auxiliary solvent or diluent. It is known to those skilled in the art of pharmaceuticaly technology that ethanol is widely used as pharmaceuticaly excipient, diluent. Alternatively, ethanol can be removed from the final solution of the present invention by evaporation under high vacuum at temperatures ⁇ 40 °C, without negative effect upon its stability. Finally, the reaction product, the solution, is only diluted with water or 1 , 2-propylene glycol up to the nominal concentration of silicon (Si), filtered, and paked into plastic bottles.
  • Si silicon
  • room temperature refers to the temperature interval: 20-25 °C. All percentage (%) portions of ingredients are expressed as weight (w/w) portions.
  • TEOS tetraethyl orthosilicate
  • tetraethyl orthosilicate NaOH; 1.00 g; 0.025 mol; 2 mol. equiv.
  • TEOS tetraethyl orthosilicate
  • the reaction mixture was stirred at room temperature for 6 h.
  • salicylic acid (1.74 g; 0.0126 mol; 1 mol. equiv.) was added to the reaction mixture during 30 minutes with vigorous stirring.
  • the reaction mixture was stirred at room temperature for 1 h.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Inorganic Chemistry (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Birds (AREA)
  • Dermatology (AREA)
  • Zoology (AREA)
  • Plant Pathology (AREA)
  • Environmental Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Agronomy & Crop Science (AREA)
  • Dentistry (AREA)
  • Engineering & Computer Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Emergency Medicine (AREA)
  • Cosmetics (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une formulation qui sert de source de silicium (Si) hautement biodisponible consistant en : (i) acide ortho-silicique (H4SiO4), de 0,01-8% p/p ; (ii) acide salicylique (1), de 1-2 équivalents molaires par rapport à H4SiO4 ; (iii) acide pharmaceutiquement acceptable, de 0,1-4 équivalents molaires par rapport à H4SiO4 ; ou base pharmaceutiquement acceptable, dans des quantités de 2 équivalents molaires par rapport à l'acide salicylique (1); et (iv) diluant, sélectionné parmi le groupe consistant en : eau purifiée, 1,2‑propylèneglycol, glycérol, éthanol, ou leurs mélanges, dans des quantités allant jusqu'à 100% p/p de la formulation. La présente invention concerne la préparation et l'utilisation de la formulation qui fournit tous les effets thérapeutiques positifs connus de l'acide ortho-silicique et de l'acide salicylique chez l'homme et les animaux, et les bénéfices de l'utilisation pour les plantes.
PCT/HR2011/000034 2010-09-06 2011-08-31 Solution stabilisée d'acide ortho-silicique à base d'acide salicylique comme inhibiteur efficace de sa polymérisation, sa préparation et son utilisation Ceased WO2012032364A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HR20100494 2010-09-06
HRP20100494A 2010-09-06

Publications (1)

Publication Number Publication Date
WO2012032364A1 true WO2012032364A1 (fr) 2012-03-15

Family

ID=44764182

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/HR2011/000034 Ceased WO2012032364A1 (fr) 2010-09-06 2011-08-31 Solution stabilisée d'acide ortho-silicique à base d'acide salicylique comme inhibiteur efficace de sa polymérisation, sa préparation et son utilisation

Country Status (1)

Country Link
WO (1) WO2012032364A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014185794A1 (fr) * 2013-05-15 2014-11-20 Przedsiębiorstwo INTERMAG Sp. z o.o. Formulation de silicium dotée de propriétés de stimulation de croissance de plantes, procédé de préparation d'une formulation de silicium dotée de propriétés de stimulation de croissance de plantes et son utilisation
EP3549578A1 (fr) * 2018-04-06 2019-10-09 Bio Minerals N.V. Formulation d'acide silicique et son utilisation
WO2021014240A1 (fr) 2019-07-25 2021-01-28 Upl Limited Nouvelles combinaisons agrochimiques
GB2588213A (en) * 2019-10-16 2021-04-21 Maxstim Ltd Improvements in, and relating to, biostimulants
WO2021259731A1 (fr) * 2020-06-26 2021-12-30 Olmix Utilisation d'une composition organo-minerale par application foliaire pour stimuler le developpement des plantes en presence d'au moins un stress abiotique ou d'un stress biotique
EP4039666A1 (fr) 2021-02-05 2022-08-10 Maxstim Limited Compositions liquides biostimulantes des plantes à base de silicium
US11878031B2 (en) 2018-10-05 2024-01-23 Bio Minerals N.V. Silicic acids for use in the treatment of periodontitis
WO2024078282A1 (fr) * 2022-10-10 2024-04-18 淄博乐悠悠农业科技有限公司 Pansement liquide pour favoriser la cicatrisation des plaies

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1388330A (en) * 1971-10-25 1975-03-26 Gueyne J Method of preparing stable aqueous solutions of organosilicic compounds and the resulting products and applications thereof
WO1995021124A1 (fr) 1994-02-07 1995-08-10 Bio Pharma Sciences B.V. Composition renfermant de l'acide ortho-silicique stabilise, et composition biologique
US6197986B1 (en) * 1997-03-24 2001-03-06 Exsymol S.A.M. Compounds containing biologically active silicon, which are under solid form
EP1371289A1 (fr) 2002-03-20 2003-12-17 Bio Minerals N.V. Complexe choline-acide silicique
WO2004016551A1 (fr) 2002-08-12 2004-02-26 Bio Minerals N.V. Procede pour la preparation d'un acide siliceux comprenant un extrudat, extrudat, son utilisation et composition pharmaceutique comprenant ledit extrudat
US20060178268A1 (en) 2002-05-31 2006-08-10 Sabalo N.V. Aqueous solution of non-colloidal silicic acid and boric acid

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1388330A (en) * 1971-10-25 1975-03-26 Gueyne J Method of preparing stable aqueous solutions of organosilicic compounds and the resulting products and applications thereof
WO1995021124A1 (fr) 1994-02-07 1995-08-10 Bio Pharma Sciences B.V. Composition renfermant de l'acide ortho-silicique stabilise, et composition biologique
US5922360A (en) 1994-02-07 1999-07-13 Bio Pharma Sciences B.V. Stabilized orthosilicic acid comprising preparation and biological preparation
US6197986B1 (en) * 1997-03-24 2001-03-06 Exsymol S.A.M. Compounds containing biologically active silicon, which are under solid form
EP1371289A1 (fr) 2002-03-20 2003-12-17 Bio Minerals N.V. Complexe choline-acide silicique
US20060178268A1 (en) 2002-05-31 2006-08-10 Sabalo N.V. Aqueous solution of non-colloidal silicic acid and boric acid
WO2004016551A1 (fr) 2002-08-12 2004-02-26 Bio Minerals N.V. Procede pour la preparation d'un acide siliceux comprenant un extrudat, extrudat, son utilisation et composition pharmaceutique comprenant ledit extrudat

Non-Patent Citations (24)

* Cited by examiner, † Cited by third party
Title
A. LASSUS: "Colloidal silicic acid for oral and topical treatment of aged skin, fragile hair and brittle nails in females", J. INT. MED. RES., vol. 21, 1993, pages 209, XP055182916
A. LASSUS: "Colloidal silicic acid for the treatment of psoriatic skin lesions, arthropathy and onychopathy. A pilot study", J. INT. MED. RES., vol. 25, 1997, pages 206
A. SCHIANO, F. EISINGER, P. DETOLLE: "Silicium, tissu osseux et immunite", REVUE DU RHUMATISME, vol. 46, 1979, pages 483
C. D. SEABORN, F. H. NIELSEN: "Silicon deprivation decreases colagen formation in wounds and bone, and ornithine transaminase enzyme activity in liver", BIOL. TRACE ELEMENT RES., vol. 89, 2002, pages 251
D. KUSTRAK: "Pharmacognosy and phytopharmacy (in Croatian", GOLDEN MARKETING-TEHNICKA KNJIGA, ZAGREB, CROATIA, 2005
D. M. REFFITT, N. OGSTON, R. JUGDAOHSINGH: "Orthosilicic acid stimulates collagen type I synthesis and osteoblast-like cells in vitro", BONE, vol. 32, 2003, pages 127
D. M. REFFITT, R. JUGDAOHSINGH, R. P. H. THOMPSON: "silicic acid: its gastrointestinal uptake and urinary excretion in man and effects on aluminium excretion", J. INORG. BIOCHEM., vol. 76, 1999, pages 141
E. M. CARLISLE, C. SUCHIL: "Silicon and ascorbate interaction in cartilage formation in culture", FED. PROC., vol. 42, 1983, pages 398
E. M. CARLISLE, D. L. GARVEY: "The effect of silicon on formation of extra-cellular matrix components by chondrocytes in culture", FED. PROC., vol. 41, 1982, pages 461
E. M. CARLISLE: "A relation between silicon and calcium in bone formation", FED. PROC., vol. 29, 1970, pages 265
E. M. CARLISLE: "A requirement for silicon for bone growth in culture", FED. PROC., vol. 37, 1978, pages 1123
E. M. CARLISLE: "Silicon: a requirement in bone formation independent of vitamin D", CALCIF. TISSUE INT., vol. 33, 1981, pages 27, XP009036273
H. A. CURRIE, C. C. PERRY: "Silica in Plants: Biological, Biochemical and Chemical Studies", ANN. BOTANY, vol. 100, 2007, pages 1383 - 1389
H. YOKOI, S. ENOMOTO: "Effect of degree of polymerization of silicic acid on the gastrointestinal absorption of silicate in rats", CHEM. PHARM. BULL., vol. 27, 1979, pages 1733
J. D. BIRCHALL, J. S. CHAPPELL: "The chemistry of aluminium and silicon in relation to Alzheimer's disease", CLIN. CHEM., vol. 34, 1980, pages 265
J. W. DOBBIE, M. J. SMITH: "Silicate nephrotoxicity in the experimental animal: the missing factor in analgesic nephropathy", SCOTISH MED. J., vol. 27, 1982, pages 10
K. SCHWARTZ: "A bound form of silicon in glycosaminoglycans and polyuronides", PROC. NAT. ACAD. SCI. USA, vol. 70, 1973, pages 1608, XP002524735, DOI: doi:10.1073/pnas.70.5.1608
K. VAN DYCK, R. VAN CAUWENBERGH, H. ROBBERECHT: "Bioavailability of silicon from food and food supplements", FRESENIUS J. ANAL. CHEM., vol. 363, 1999, pages 541, XP002633342, DOI: doi:10.1007/s002160051243
M. R. CALOMME, D. A. V. BERGHE: "Supplementation of calves with stabilised orthosilicic acid effect on the Si, Ca, Mg and P concentration in serum and the collagen concentration in skin and cartilage", BIOL. TRACE ELEMENT RES., vol. 56, 1997, pages 153, XP000925562
R. JUGDAOHSINGH, D. M. REFFITT, C. OLDHAM: "Oligomeric but not monomeric silica prevents aluminium absorption in human", AM. J. CLIN. NUTR., vol. 71, 2000, pages 944
R. JUGDAOHSINGH, S. H. ANDERSON, K. L. TUCKER: "Dietary silicon intake and absorption", AM. J. CLIN. NUTR., vol. 75, 2002, pages 887
R. JUGDAOHSINGH: "Silicon and bone health", J. NUTR. HEALTH AGING, vol. 11, 2007, pages 99, XP055189787
R. JUGDAOHSINGH: "Soluble silica and aluminium bioavailability", PHD THESIS, 1999
S. SPRIPANYAKORN, R. JUNGDAOHSINGH, R. P. H. THOMPSON, J. J. POWELL: "Dietary silicon and bone health", NUTR. BULL., vol. 30, 2005, pages 222

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014185794A1 (fr) * 2013-05-15 2014-11-20 Przedsiębiorstwo INTERMAG Sp. z o.o. Formulation de silicium dotée de propriétés de stimulation de croissance de plantes, procédé de préparation d'une formulation de silicium dotée de propriétés de stimulation de croissance de plantes et son utilisation
IL277892B1 (en) * 2018-04-06 2024-06-01 Bio Minerals Nv Silicic acid formulation and use thereof
EP3549578A1 (fr) * 2018-04-06 2019-10-09 Bio Minerals N.V. Formulation d'acide silicique et son utilisation
WO2019193200A1 (fr) * 2018-04-06 2019-10-10 Name: Bio Minerals N.V. Formulation d'aide silicique et son utilisation
US12447176B2 (en) 2018-04-06 2025-10-21 Bio Minerals N.V. Silicic acid formulation and use thereof
IL277892B2 (en) * 2018-04-06 2024-10-01 Bio Minerals Nv Silicic acid formulation and use thereof
AU2019247705B2 (en) * 2018-04-06 2024-07-11 Bio Minerals N.V. Silicic acid formulation and use thereof
US11878031B2 (en) 2018-10-05 2024-01-23 Bio Minerals N.V. Silicic acids for use in the treatment of periodontitis
WO2021014240A1 (fr) 2019-07-25 2021-01-28 Upl Limited Nouvelles combinaisons agrochimiques
EP4003019A4 (fr) * 2019-07-25 2023-08-02 UPL Limited Nouvelles combinaisons agrochimiques
GB2588213A (en) * 2019-10-16 2021-04-21 Maxstim Ltd Improvements in, and relating to, biostimulants
GB2588213B (en) * 2019-10-16 2023-08-09 Maxstim Ltd Improvements in, and relating to, biostimulants
CN115768266A (zh) * 2020-06-26 2023-03-07 奥密克斯 有机矿物组合物通过叶面施用以在存在至少一种非生物胁迫或生物胁迫的情况下刺激植物发育的用途
FR3111767A1 (fr) * 2020-06-26 2021-12-31 Olmix Utilisation d’une composition organo-minérale par application foliaire pour stimuler le développement des plantes en présence d’au moins un stress abiotique ou d’un stress biotique
WO2021259731A1 (fr) * 2020-06-26 2021-12-30 Olmix Utilisation d'une composition organo-minerale par application foliaire pour stimuler le developpement des plantes en presence d'au moins un stress abiotique ou d'un stress biotique
EP4039666A1 (fr) 2021-02-05 2022-08-10 Maxstim Limited Compositions liquides biostimulantes des plantes à base de silicium
WO2024078282A1 (fr) * 2022-10-10 2024-04-18 淄博乐悠悠农业科技有限公司 Pansement liquide pour favoriser la cicatrisation des plaies
US12303611B2 (en) 2022-10-10 2025-05-20 Zibo Leyouyou Agricultural Technology Co., Ltd. Liquid dressing for promoting wound healing

Similar Documents

Publication Publication Date Title
WO2012032364A1 (fr) Solution stabilisée d'acide ortho-silicique à base d'acide salicylique comme inhibiteur efficace de sa polymérisation, sa préparation et son utilisation
ES2402215T5 (es) Suspensión que contiene nanopartículas de ácido silícico coloidal estabilizadas con hidronio, formulación obtenida a partir de dicha suspensión diluida, polvo obtenido as partir de dicha suspensión deshidratada, composiciones obtenidas a partir de dicho polvo, preparación y uso
Jurkić et al. Biological and therapeutic effects of ortho-silicic acid and some ortho-silicic acid-releasing compounds: New perspectives for therapy
WO2010018418A1 (fr) Formulation à base de clinoptilolite micronisée utilisée en tant qu’agent thérapeutique produisant un silicium extrêmement biodisponible
CN100354236C (zh) 非胶体硅酸和硼酸的水溶液
WO2012035364A1 (fr) Solution stabilisée d'acide ortho-silicique, sa préparation et son utilisation
ES2216017T3 (es) Formulaciones intravenosas de alendronato.
MX2012011375A (es) Solucion de silicato soluble biodisponible estabilizado.
AU2017201085B2 (en) Strontium based compositions and formulations for pain, pruritus, and inflammation
BR0004827B1 (pt) Complexo à base de ácido ortossilícico biologicamente assimilável, processo de preparação do mesmo, composição cosmética ou farmacêutica, e, complemento nutritivo
BR112014023473B1 (pt) Complexos contendo estrôncio administrados topicamente para o tratamento de dor, prurido e inflamação
ES2251684T3 (es) Complejo de acido colina-silicico con osmolitos y elementos traza divalentes.
AU616755B2 (en) Topically applied gold organic complex
US20120220752A1 (en) Tri-amino releasing fulvate
JP6572475B2 (ja) 芳香環系を有する有機酸又はエステルの改良された粉末配合物
JPS6121528B2 (fr)
RU2006133305A (ru) Применение 2, 5-дигидроксибензолсульфоновой кислоты для получения лекарственных препаратов, применяемых для лечения ангиозависимых заболеваний
CN1200366A (zh) 新l－苏糖酸衍生物
HRP20140504A2 (hr) Stabilizirana formulacija ortho-silicijeve kiseline, njezina priprava i upotreba
CN119894823A (zh) 稳定的硅酸溶液
JP5564648B2 (ja) 水溶性酸化亜鉛組成物
HRP20100460A2 (hr) Formulacija na temelju u vodi netopljivog izvora ortho-silicijeve kiseline te asparaginske kiseline kao učinkovitog inhibitora njezine polimerizacije
JP3058659B2 (ja) 生物的に利用可能な形態のミネラル
US20140255465A1 (en) Process For The Preparation Of A Non-Corrosive Base Solution And Methods Of Using Same
CN116390711B (zh) 包含有机硅烷醇化合物的组合物及应用

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 11767052

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 11767052

Country of ref document: EP

Kind code of ref document: A1