WO2005076731A2 - Compositions a haute teneur en sel, procedes de production et d'utilisation de ces compositions - Google Patents

Compositions a haute teneur en sel, procedes de production et d'utilisation de ces compositions Download PDF

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Publication number
WO2005076731A2
WO2005076731A2 PCT/IL2005/000169 IL2005000169W WO2005076731A2 WO 2005076731 A2 WO2005076731 A2 WO 2005076731A2 IL 2005000169 W IL2005000169 W IL 2005000169W WO 2005076731 A2 WO2005076731 A2 WO 2005076731A2
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salt
water
another embodiment
oil
emulsion
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PCT/IL2005/000169
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English (en)
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WO2005076731A3 (fr
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Amit Lotan
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Nidaria Technology Ltd.
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Publication of WO2005076731A2 publication Critical patent/WO2005076731A2/fr
Publication of WO2005076731A3 publication Critical patent/WO2005076731A3/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials

Definitions

  • the present invention relates to high salt compositions, methods of producing same, and methods their use for inhibiting nematocyst or polar capsule discharge and protecting a subject from nematocyst sting.
  • the members of the phylum Cnidaria (e.g., jellyfish, sea anemone and coral) and the phylum Myxozoa are all equipped with stinging subcellular organelles known as nematocysts, cnidocysts, or polar capsules.
  • the nematocysts are located in specialized cells (nematocytes) and consist of capsules each containing a condensed tubule with potent toxins and threads. When nematocysts discharge, the tubule penetrates its target organism and releases its toxins. The threads arrayed on the tubule enhance the anchoring and attachment of the nematocyst tubule to its target. Nematocysts are involved in target recognition, toxin delivery, infection and attachment.
  • nematocysts All members of the phyla Cnidaria and Myxozoa contain nematocysts of varying sizes, shapes and types. These different types of cnidocysts function in diverse biological roles including capture of prey, toxin delivery, recognition, attachment, adherence and infection. Although best known for their stinging capabilities, nematocysts also play a key role in recognition, attachment and infection. For example, parasites from the phylum Myxozoa use nematocysts (polar capsules) to recognize and infect their hosts.
  • the main body of the nematocyte cell consists of a dense capsule, the nematocyst, within which is a highly folded eversible tubule. Discharge (eversion) of this tubule is driven by the build up of a high internal hydrostatic pressure of approximately 150 atmospheres within the capsule. The eversion of the internally folded tubule occurs within 3 microseconds at accelerations of up to 40,000 X g, one of the most rapid mechanical events in cell biology.
  • the nematocyte can be sub-divided into 3 morphological compartments with different functional entities: the capsule lumen and wall, the tubule and the sensory organelles.
  • the capsule wall and lumen are the main components involved in developing the driving force for nematocyst discharge.
  • the tension on the inner capsule wall during nematocyst discharge reaches up to 375 MPa.
  • the strong capsule wall is highly permeable to water with a pore size of 600 Dalton.
  • concentrations of up to 0.5 M of cations such as Ca ++ , Mg " * " or K + can be found.
  • the anionic counterparts are represented by poly-. gamma.
  • PGA -L-glutamatic acid
  • the second compartment of the nematocyst is a highly condensed eversible tubule.
  • This tubule serves the main role in nematocyte biological function, namely, the interaction or delivery of substances from the cnidarian or myxozoan into its target.
  • the tubule which is 200-850 ⁇ m when elongated, is twisted more than a hundred times around its axis and is packed into the 3-10 ⁇ m diameter of the nematocyst.
  • Hollow barbs, arrayed on the inner surface of the tubule become everted during discharge and play an important role in the penetration and anchoring of the tubule into its prey.
  • Toxins contained on the outer surface before discharge, are delivered through the barbs after the nematocyst is anchored.
  • Nematocysts therefore, effectively and efficiently penetrate deeply into their target, making their removal difficult, and treatment of thus deposited toxin difficult as well.
  • nematocyst stings have been treated with antidotes such as steroids, aluminum sulfate/surfactant and antihistamines.
  • compositions comprising calcium chloride and magnesium chloride have been shown to inhibit Nematocyst discharge.
  • Widespread use of a topical composition which inhibits nematocyst discharge necessitates its ease of application, and it's inherent ability to prevent cation solubility in seawater to provide optimal protection. It's ready formulation in compositions providing additional benefits is clearly desirable, such as, for example, its formulation with sunscreens.
  • the present invention provides, in one embodiment, a composition for inhibiting the discharge of nematocysts or polar capsules, comprising a salt in water in oil emulsion, wherein said salt is inorganic and is at a concentration of 32-65 %.
  • the salt comprises a calcium, magnesium, potassium, zinc, titanium, gadolinium, lanthanum or sodium cation, or combinations thereof.
  • the salt comprises a chloride anion.
  • the salt comprises calcium, magnesium, and lanthanum cations.
  • the salt is a chloride salt of calcium, magnesium, and lanthanum cations, which, in another embodiment, is at a concentration of at least 9 % for each salt.
  • the composition further comprises an emulsifier, which in another embodiment comprises laurylmethicone copolyol.
  • the composition further comprises an antihistamine, or in another embodiment, a glycosaminoglycan. or in another embodiment, a sunscreen, or in another embodiment, a combination thereof.
  • the composition is water-proof.
  • the oil phase of the emulsion comprises 20-40 %. In another embodiment, the oil phase of the emulsion comprises mineral oil, sodium alginate or spent grain wax, or combinations thereof.
  • this invention provides a method of preparing a composition for topical application, which inhibits the discharge of nematocytes or polar capsules, comprising incorporating the salt in water in oil emulsion into a composition, such that the final cation concentration of the composition is 2 - 12 %.
  • this invention provides a process for the preparation of a high salt in water in oil emulsion, comprising dissolving at least one inorganic salt in water to form solution A, dissolving at least 1 other inorganic salt at a temperature of at least 60 ° C in solution A to form solution B, dissolving at least 1 other inorganic salt at a temperature of at least 60 ° C in solution B to form solution C, and combining solution C with an oil phase so as to obtain a homogeneous high salt in water in oil emulsion, wherein the final salt concentration in said high salt in water in oil emulsion ranges from 32 - 65 %.
  • the inorganic salt comprises a calcium, magnesium, potassium, zinc, titanium, gadolinium, lanthanum or sodium cation, or combinations thereof.
  • the salt comprises a chloride anion.
  • the salt comprises calcium, magnesium, and lanthanum cations.
  • the salt is a chloride salt of calcium, magnesium, and lanthanum cations.
  • the calcium, magnesium and lanthanum chloride salt is at a concentration of at least 9 % for each salt.
  • the emulsion comprises an emulsifier, which in another embodiment is laurylmethicone copolyol. In another embodiment, the emulsion comprises 1-20 % water.
  • the oil phase of the emulsion comprises 20-40 %.
  • the oil phase of the emulsion comprises an antihistamine, or in another embodiment, a glycosaminoglycan, or in another embodiment, a sunscreen, or a combination thereof.
  • the oil phase of the emulsion comprises mineral oil, sodium alginate or spent grain wax, or combinations thereof.
  • Figure 1 demonstrates that compositions comprising a high salt in water in oil emulsion further comprising a sunscreen are water-proof. The determination of the percent CaCl concentration retained on cotton squares following exposure to continuously agitated sea water was determined as a function of time.
  • the present invention provides, in one embodiment, a composition for inhibiting the discharge of nematocysts or polar capsules, comprising a salt in water in oil emulsion, wherein the salt is inorganic and is at a concentration of 32-65 %.
  • compositions of this invention are specifically useful in protecting against stinging marine organisms such as Cnidaria and Myxozoa.
  • nematocyst or “cnidocyst” or “polar capsule” refer to subcellular stinging structures found in the nematocytes or cnidocytes, which are capable of penetrating, anchoring into and injecting a substance such as a toxin into a target organism.
  • nematocyte or "cnidocyte” or “cnidoblast” refer to the specialized cells that contain the nematocysts.
  • Non-limiting examples of classes of the phylum Cnidaria that possess cnidocytes include, for example, Hydrozoa, Anthozoa, Myxozoa and Scyphozoa.
  • jellyfish examples include, but are not limited to, Aurelia sp., Pelagia sp., Chrysaora sp., Anthoplaura sp., Rhopilema sp., Physalia sp., Cyanea sp., Linuche sp., Catostylus sp., Carybdea sp., Chironex sp., Stomolophus sp., R iozostoma sp., Corinactis sp. and the like.
  • the nematocysts are discharged from a stinging organism selected from the phyla Cnidaria and Myxozoa.
  • the stinging marine organism is Cnidaria consisting of jellyfish, sea anemone and coral.
  • the present invention in one embodiment, furthers the development of compositions for prevention of nematocyst or polar capsule discharge by providing a high salt formulation that is stable over time, and, in another embodiment, in a form that can be "reformulated” to comprise other ingredients that, in another embodiment, provide additional beneficial effects.
  • reformulation refers to, in one embodiment, the property of the composition such that other components may be added to the composition that are desirable, and do not affect the stability of the high salt in water in oil emulsion.
  • reformulation entails producing a composition with a reduced concentration of salt.
  • the reformulation of the compositions of this invention provides for a composition with a final cations concentration of between 2 and 12 %.
  • this invention provides a method of preparing a composition for topical application, which inhibits the discharge of nematocytes or polar capsules, comprising incorporating the salt in water in oil emulsion into a composition, such that the final cation concentration of the composition is 2 - 12 %.
  • the salt in the compositions of this invention comprise a calcium, magnesium, potassium, zinc, titanium, gadolinium, lanthanum or sodium cation, or combinations thereof.
  • the compositions specifically comprise Ga or La , or in another embodiment, Ca or Mg , or in another embodiment, a combination thereof, which, in another embodiment effectively inhibits the discharge of nematocysts or polar capsules.
  • the term "cation" refers, in another embodiment, to any positively charged ion.
  • the cation is a metal cation.
  • the cation is any of the species listed above, or one derived from any suitable cation source.
  • the salts of this invention are halo salts such as chlorides, bromides and iodides.
  • the salt is a chloride salt
  • the salt is a chloride salt of calcium, magnesium, and lanthanum cations, which, in another embodiment, is at a concentration of at least 9 % for each salt.
  • the cation in the salts of this invention is at an amount sufficient to inhibit, limit, repress, palliate or prevent the discharge of nematocysts or polar capsule and/or to inhibit, limit, repress, palliate or prevent Cnidaria sting.
  • the concentration of each cation is from 5 to 30 %. In one embodiment, the concentration of each cation is from 9 to 30 %. In one embodiment, the concentration of the cation is from 9 to 12 %. In one embodiment, the concentration of the cation is from 9 to 15 %. In one embodiment, the concentration of the cation is from 9 to 20 %.
  • the concentration of the cation is from 9 to 25 %. In one embodiment, the concentration of the cation is from 10 to 16 %. In one embodiment, the concentration of the cation is from 10 to 20 %. In one embodiment, the concentration of the cation is from 15 to 20 %. In one embodiment, the concentration of the cation is from 15 to 22 %. In one embodiment, the concentration of the cation is from 15 to 25 %. In one embodiment, the concentration of the cation is from 15 to 30 %. In one embodiment, the concentration of the cation is from 20 to 30 %. In one embodiment, the concentration of the cation is from 20 to 25 %.
  • the total salt concentration of the salt in water in oil emulsion, and, in another embodiment, compositions comprising the same is from 25 to 80 %. In one embodiment, the total salt concentration is from 28 to 65 %. In one embodiment, the total salt concentration is from 30 to 65 %. In one embodiment, the total salt concentration is from 32 to 65 %. In one embodiment, the total salt concentration is from 35 to 65 %. In one embodiment, the total salt concentration is from 32 to 42 %. In one embodiment, the total salt concentration is from 45 to 60 %. In one embodiment, the total salt concentration is from 37 to 45 %. In one embodiment, the total salt concentration is from 32 to 50 %. In one embodiment, the total salt concentration is from 37 to 55 %.
  • the total salt concentration is from 32 to 40%. In one embodiment, the total salt concentration is from 37 to 60 %. In one embodiment, the total salt concentration is from 37 to 70 %. In one embodiment, the total salt concentration is from 37 to 75 %. In one embodiment, the total salt concentration is from 45 to 50 %. In one embodiment, the total salt concentration is from 45 to 55 %. In one embodiment, the total salt concentration is from 45 to 60 %. In one embodiment, the total salt concentration is from 45 to 70 %. In one embodiment, the total salt concentration is from 55 to 80 %. In one embodiment, the total salt concentration is from 55 to 60 %. In one embodiment, the total salt concentration is from 55 to 65 %. In one embodiment, the total salt concentration is from 55 to 70 %.
  • the total salt concentration is from 55 to 75 %. In one embodiment, the total salt concentration is from 55 to 80 %. In one embodiment, the total salt concentration is from 60 to 65 %. In one embodiment, the total salt concentration is from 60 to 70 %. In one embodiment, the total salt concentration is from 60 to 75 %. In one embodiment, the total salt concentration is from 60 to 80 %. In one embodiment, the total salt concentration is from 65 to 70 %. In one embodiment, the total salt concentration is from 65 to 75 %. In one embodiment, the total salt concentration is from 65 to 80 %.
  • this invention provides a process for the preparation of a high salt in water in oil emulsion, comprising dissolving at least one inorganic salt in water to form solution A, dissolving at least 1 other inorganic salt at a temperature of at least 60 ° C in solution A to form solution B, dissolving at least 1 other inorganic salt at a temperature of at least 60 ° C in solution B to form solution C, and combining solution C with an oil phase so as to obtain a homogeneous high salt in water in oil emulsion, wherein the final salt concentration in said high salt in water in oil emulsion ranges from 55 - 80 %.
  • the phrase "high salt in water in oil” refers to an emulsion whose water phase comprises roughly 10 % water, and 90 % total salt, or in another embodiment, 15 % water, and 85 % total salt, or in another embodiment, 20 % water and 80 % total salt.
  • the water phase will comprise water at a range of between 10 and 25 %.
  • the water phase will comprise a total salt concentration of between 75 - 90 %.
  • the water phase will be heated to a temperature corresponding to the melting point of the salts.
  • the water phase will comprise at least 3 inorganic salts.
  • the water phase will comprise at least 2 inorganic salts, which in another embodiment are chloride salts of Lanthanum and Magnesium, or, in another embodiment, Lanthanum and Calcium.
  • the presence of the Lanthanum enhances the solvation of other inorganic salts comprising the water phase, such that greater concentrations of the salts become solubilized.
  • combining multiple salts enables solubilization at higher concentrations, for each salt, than would occur with each salt alone.
  • the water phase is then combined into the oil phase, in the process of this invention.
  • the combination of the phases is conducted by means well known to one skilled in the art, and may include, in one embodiment, homogenization.
  • the high salt in water in oil emulsion is prepared as exemplified hereinbelow, which provided a stable emulsion that was waterproof.
  • the oil phase of the emulsion comprises 20-40 %.
  • the oil phase of the emulsion comprises mineral oil, sodium alginate or spent grain wax, or combinations thereof.
  • the high salt in water in oil emulsion, in a composition is added to an oil phase, of the composition.
  • the high salt in water in oil emulsion is within a composition comprising an additional emulsion, which differs in properties from the high salt in water in oil emulsion. Examples of such compositions are presented herein in Examples 2 and 3, hereinbelow.
  • the process includes the use of hydrated salts in the preparation of the emulsion.
  • a water in oil emulsion of 60% salt is achieved, using hydrated salts, where 1-25 % CaCl 2 and 1-25 % of LaCl 3 and 1-25 % of MgCl 2 is introduced into an emulsion containing 1-10 % laurylmethicone copolyol, 1-20 % mineral oil, 1-20 % waterproofing compound, 1-10 % wax, 0.1-3 % sodium alginate and 0.1-2 % spent grain wax.
  • the final concentration of LaC13 is 1-10%, or in another embodiment, 5-12%, or in another embodiment, 8-15%, or in another embodiment, 9-17%, or in another embodiment, 12- 19%, or in another embodiment, 13-18%, or in another embodiment, 5-10%, or in another embodiment, 11-17%, or in another embodiment, 14-19%, or in another embodiment, 15-20%, or in another embodiment, 10-25%.
  • the final concentration of CaCl is 1-10%, or in another embodiment, 5-12%, or in another embodiment, 8-15%, or in another embodiment, 9-17%, or in another embodiment, 10- 19%, or in another embodiment, 11-18%, or in another embodiment, 5-10%, or in another embodiment, 9-20%, or in another embodiment, 12-17%, or in another embodiment, 13-18%, or in another embodiment, 14-19%, or in another embodiment, 15-20%, or in another embodiment, 10-25%.
  • the final concentration of MgCl 2 is 1-10%, or in another embodiment, 5-12%, or in another embodiment, 8-15%, or in another embodiment, 9-17%, or in another embodiment, 10- 19%, or in another embodiment, 11-18%, or in another embodiment, 12-19%, or in another embodiment, 13-20%, or in another embodiment, 14-20%, or in another embodiment, 15-22 %, or in another embodiment, 5-10%, or in another embodiment, 9- 20%, or in another embodiment, 10-25%.
  • the process for preparing the salt in water in oil emulsion comprises establishing a melting point for a particular combination of salts, and integrating the melted salts in the oil silicon phase, as described and exemplified herein.
  • the process enables production of an emulsion, with a high salt concentration, wherein the salt does not escape into a water phase, when exposed to an aqueous environment.
  • the phrase "water-proof salt in water in oil emulsion” refers to the characteristic of this emulsion to provide an emulsion stable over time, in which the salts do not "escape" into an aqueous environment, but rather are maintained in the emulsion, when thus exposed.
  • the present invention provides a high salt in water in oil emulsion.
  • the emulsion of this invention is a mixture of two immiscible liquids, i.e. liquids that are not mutually soluble, that are mechanically agitated and shaken so thoroughly together that one liquid forms drops in the other one, giving the mixture the appearance of a homogeneous liquid.
  • an emulsifier is added to the two immiscible liquids, wherein one becomes continuous and the other remains in droplet form.
  • emulsifiers are molecules with non-polar and polar parts that are able to reside at the interface of the two immiscible liquids.
  • the emulsifier may comprise laurylmethicone copolyol.
  • the emulsifier may comprise polyglyceryl-2 dipolyhydroxystearate, ciclopentasiloxane and PEG- 12, dimethicone crosspolymer, ciclopentasiloxane and PEG/PPG- 19/19 dimethicone, ciclopentasiloxane and PEG/PPG-18/18 dimethicone, lauryl PEG/PPG -18/18 methicone, Peg-30 dipolyhydroxy stearate or cetyl dimethicone copolyol.
  • compositions of this invention will comprise the high salt in water in oil emulsion, and, in another embodment, an antihistamine, or in another embodiment, a glycosaminoglycan, or in another embodiment, a sunscreen, or in another embodiment, a combination thereof.
  • the composition comprises agents that render the composition water-proof.
  • compositions of this invention can be reformulated for the following applications: topical formulations, emulsions, sprays, liquid dispersions, solutions, skin creams, face creams, lotions, solid sticks or ointments.
  • Such compositions may contain emulsifiers, water, emollients, dry-feel agents, waterproofing agents, preservatives, antioxidants, pigments, anti-histamines, anti-foaming agents and fragrances as well as any other class of materials whose presence may be desirable, known to those skilled in the art.
  • compositions described herein are effective at inhibiting nematocyst or polar capsule discharge when applied topically prior to exposure to nematocysts, and in another embodiment, are effective when reformulated to comprise a lower concentration of the cations.
  • compositions and/or formulations described herein are topical formulations, or are reformulated to be topical formulations, which are suited for topical application to a subject.
  • the compositions described herein comprise a vehicle suitable for topical application.
  • Topical formulations containing compositions within the present invention create physical barriers to minimize skin stimulant secretion and are, themselves, not stimulants. Formulations should be water-proof so as to be useful for swimmers and divers.
  • Examples of vehicles suitable for topical application include, but are not limited to, dextran, dextran sulfate, agarose, phosphatidyl ethanolamine, cholesterol, cholesterol palmitate, palmitic acid, oleic acid, lysolecitin, phosphatidyl choline, phosphatidyl serine, phosphatidyl inositol, squalene, phenyl trimethicone, stearic acid, propylene glycol sterate, petrolatum, stearoxytrimethyl-silane, stearyl alcohol.
  • Other vehicles are known to those skilled in the art. Silicone polymers are preferred as they provide good barriers, are -water-proof and do not stimulate nematocyst discharge.
  • compositions of the present invention are incorporated in a vehicle that comprises a lipid.
  • a vehicle that comprises a lipid.
  • lipid type materials and mixtures of materials are suitable for use as the vehicle in the compositions of the present invention.
  • compositions of this invention are reformulated to comprise a water-in-oil-in water emulsion, the oil in a continuous phase containing dispersed water droplets, which are themselves dispersed in a continuous water phase.
  • a water-in-oil-in water emulsion the oil in a continuous phase containing dispersed water droplets, which are themselves dispersed in a continuous water phase.
  • compositions of this invention, or reformulated compositions may further comprise an emollient, which in another embodiment, refers to an oil-containing agent, which helps to smooth and soften the skin, and may also reduce its roughness, cracking or irritation.
  • the emollient may include mineral oil, lanolin oil, coconut oil, cocoa butter, olive oil, almond oil, macadamia nut oil, aloe extract, jojoba oil, safflower oil, corn oil, liquid lanolin, cottonseed oil and peanut oil.
  • the emollients include Purcellin oil, perhydrosqualene, castor oil, polybutene, odorless mineral spirits, sweet almond oil, avocado oil, calophyllum oil, ricin oil, vitamin E acetate, olive oil, silicone oils such as dimethylopolysiloxane and cyclomethicone, linolenic alcohol, oleyl alcohol, isohexadecane, the oil of cereal germs such as the oil of wheat germ, isopropyl palmitate, isopropyl myristate, hexadecyl stearate, butyl stearate, decyl oleate, acetyl glycerides, the octanoates and benzoates of (C ⁇ -C ⁇ 5 ) alcohols, the octanoates and decanoates of alcohols and polyalcohols such as those of glycol and glycerol, ricin o
  • the emollients include solids or semi- solids at ambient temperatures, which, in another embodiment, may be used if admixed with mineral oil or extra heavy mineral oil in amounts sufficient to provide liquid topical compositions.
  • such solid or semi-solid emollients include hydrogenated lanolin, hydroxylated lanolin, acetylated lanolin, petrolatum, isopropyl lanolate, butyl myristate, cetyl myristate, myristyl myristate, myristyl lactate, cetyl alcohol, isostearyl alcohol and isocetyl lanolate.
  • emollients include esters of a straight or branched-chain Cio-Ci ⁇ alcohol and a straight or branched chain C 4 -C 2 n mono- and dicarboxylic acids include the straight and branched chain monocarboxylic acids substituted by hydroxy or double bonds including monocarboxylic acids such as: butanoic, pentanoic, 2- methyl- and 3 -methyl -pentanoic, 2,2-dimethylpropanoic, hexanoic, 2- methyl-, 3-methyl-, and 4-methyl-, 5-methyl- and 6-methyl-heptanoic, 2- ethylhexanoic, octanoic (caprylic), 2-methyl-, 3-methyl-, 4- methyl-, 5- methyl-, 6-methyl-, 7-methyl- and 8-methyl-nonanoic, 3,3,5- trimethylexanoic (isonanomic), decanoic (caproic), 2-methyl-, 3-methyl-,
  • the carboxylic acid is succinic acid.
  • the carboxylic acid is adipic acid.
  • the tri lower alkyl substituted benzoic acids include trimethylbenzoic acids, such as 1,1,3-trimthylbenzoic acid, 1,2, 4-trimethyl-benzoic acid (trimellitic acid), 1,3,5-trimethylbenzoic acid (trimesic acid), alkyl benzoate or C 12-15 Alkyl Benzoate.
  • trimethylbenzoic acids such as 1,1,3-trimthylbenzoic acid, 1,2, 4-trimethyl-benzoic acid (trimellitic acid), 1,3,5-trimethylbenzoic acid (trimesic acid), alkyl benzoate or C 12-15 Alkyl Benzoate.
  • trimellitic acid 1,1,3-trimthylbenzoic acid
  • trimellitic acid 1,3,5-trimethylbenzoic acid
  • trimellitic acid 1,3,5-trimethylbenzoic acid
  • alkyl benzoate or C 12-15 Alkyl Benzoate.
  • trimellitic acid trimellitic acid
  • esters of C 4 to C o monocarboxylic acids and straight and branched chain C ⁇ o-C ⁇ 6 alcohols include tridecyl neopentonate, isotridecyl isononanoate, isodecyl neopentonate, isodecyl hydroxystearate, isodecyl laurate, isodecyl myristate, isodecyl oleate, isodecyl palmitate, decyl oleate, and isocetyl palmitate (isohexadecyl hexadecanoate) and iso-hexadecyl isodecanoate (14-methylpentadecyl-8- methyinonanoate).
  • an ester of straight and branched-chain Cio- Ci 6 alcohols and C 4 -C 2 o dicarboxylic acids is decyl succinate.
  • the esters are esters of straight and branched-chain C ⁇ o-C 16 esters of tri(loweralkyl) substituted benzoic acids are the decyl, isodecyl, isotridecyl and tridecyl esters of trimethylbenzoic acids for example trimellitic acid; tridecyl trimellitate.
  • the emollient can, in another embodiment, be a mixture of tridecyltrimellitate and tridecyl stearate or a mixture of tridecyl trimellitate, tridecyl stearate, neopentyl glycol dicaprylate and neopentyl dicaprate such as is available from Lipo Chemicals Inc., Patterson, JJ. under the tradename Lipovol MOS-70.
  • compositions described herein may contain a known sunscreen. Such sunscreens are also known to those skilled in the art.
  • the sunscreens contain a UVA filter or UVB filter, or a combination thereof.
  • Oil-soluble UVB products include, in another embodiment, 3- benzylidenecamphor derivatives, 4-aminobenzoic acid derivatives, esters of cinnamic acid, derivatives of benzophenone, esters of benzylidenemalonic acid.
  • Water soluble UVA filters include, in another embodiment, salts of 2-phenylbenzimidazole-5- sulphonic acid, sulphonic acid derivatives of benzophenones and sulphonic acid derivatives of 3- benzylidenecamphor.
  • the sunscreens will comprise between about 0.1% and 10% by weight of the total preparation.
  • the sunscreen active ingredients include trade names of para-aminobenzoic acid up to about 15 weight percent or from about 5 to 15% in admixture with other sunscreen actives; cinoxate up to about 3 weight percent or about 1 to 3% in admixture; diethanolamine methoxycinnamate up to 10 weight percent or about 8 to 10% in admixture; digalloyl trioleate up to 5 weight percent or about 2 to 5% in admixture; dioxybenzone up to 3 weight percent alone or in admixture; ethyl 4- [bis(hydroxy ⁇ ropyl)] aminobenzoate up to 5 weight percent or about 1 to 5% in admixture; glyceryl aminobenzoate up to 3 weight percent or about 2 to 3% in admixture; homosalate up to 15 weight percent or about 4 to 15% in admixture;
  • oxybenzone up to 6 weight percent or about 2 to 6% in admixture; padimate up to 8 weight percent or about 1.4 to 8% in admixture; phenylbenzimidazole sulfonic acid up to 4 weight percent or about 1 to about 4% in admixture; red veterinary petrolatum up to 95 percent or about 30 to 95% in admixture; sulisobenzone up to 10 weight percent or about 5 to 10% in admixture; titanium dioxide up to 25 weight percent or about 2 to 25% in admixture; and trolamine salicylate up to 12 weight percent or about 5 to 12% in admixture.
  • sunscreens include Ethylhexyl (Octyl) Salicylate, Ethylhexyl (Octyl) Salicylate,Methylbenzylidene Camphor, Octocrylene, Bultyl Methoxydibenzoyl methane, Ethylhexyl (Octyl) Methoxycinnamate.
  • UV-B type sunscreening active ingredients include octyl para-methoxycinnamate available from Givaudan Corporation, Clifton, N.J., under the trade name of Parsol MCX and Parsol 1789, which, in another embodiment, are in the range of about 1.5 to about 7.5 weight %, or octyl salicylate available from Harmann and Riemer, Springfield, N.J., 07081, which, in another embodiment, are in the range of about 3 to about 5 weight %, of the total sunscreen composition or emulsion.
  • the amount of UV-B type sunscreening active ingredients are sufficient to give an SPF of at least 2 to 15.
  • suitable UV-A type sunscreening active ingredient include benzophenone-3, which, in another embodiment, are in the range of about 0.5 to about 6 weight %.
  • Such actives can be obtained from Rhone- Poulenc, Atlanta, Ga.
  • Sunscreen emulsions containing mixtures of UV-B and UV-A type sunscreen actives in another embodiment are sufficient to provide an SPF of 4 to 50.
  • a dry-feel modifier is, in one embodiment, an agent that gives a sunscreen a "dry feel" upon drying, and may reduce sunscreen migration and can include silazane treated silica, precipitated silica, fumed silica or mixtures thereof.
  • the dry-feel modifier can, in another embodiment, be included in the sunscreen composition in amounts ranging from about 0.1 to about five weight percent, preferably from about 0.3 to about 1.5%.
  • a waterproofing agent is added to the composition, which serves to, in one embodiment, assist in the retention of the high concentration of salts in the composition, or in another embodiment, to assist in the retention of sunscreen active ingredients, or a combination thereof.
  • the waterproofing agent may comprise copolymers derived from polymerization of octadecene-1 and maleic anhydride in accordance with the published procedures such as those in U.S. Pat. No. 3,860,700 and Reissue No. 28,475.
  • the waterproofing agent is a copolymer commercially available from Chevron Chemicals Co. under the trade name, PA- 18 polyanhydride resin.
  • the water-proofing agent may be PVP/Eicosene Copolymer, PVP/hexadecane Copolymer, Tricontanyl PVP, Acrylates/octylacrylamide copolymer, Dimethicone or Alkyl Methyl Siloxane.
  • water-proof compositions refers to, in another embodiment, an agent(s) which, when applied, in one embodiment, to the skin, affects the retention of components of the composition on the skin following exposure to water. In one embodiment, a water-proof composition will result in retention for at least 80 minutes following exposure.
  • the waterproofing agent may comprise 0.01 to about 10.0 weight percent, or in another embodiment, 1.0 to about 10.0 percent, or the composition.
  • compositions of the present invention may further comprise an antimicrobial preservative.
  • An antimicrobial preservative is, in one embodiment, a substance or preparation that destroys, prevents or inhibits the multiplication/growth of microorganisms in the sunscreen composition and may offer protection from oxidation.
  • the preservatives may comprise lower alkyl esters of para-hydroxybenzoates (parabens) such as, for example, methyl paraben, isobutyl paraben or mixtures thereof, or benzoic acid.
  • parabens para-hydroxybenzoates
  • the high salt concentration itself serves as a preservative.
  • the compositions of the present invention may further comprise an antioxidant, which may serve, in another embodiment, to prevent or delay deterioration of the composition.
  • an antioxidant extends the shelf-life of the high salt in water in oil emulsion.
  • the antioxidant may include propyl, octyl and dodecyl esters of gallic acid, butylated hydroxyanisole (BHA)(usually as a mixture of orthos and meta isomers), butylated hydroxytoluene (BHT) and nordihydroguaiaretic acid.
  • BHA butylated hydroxyanisole
  • BHT butylated hydroxytoluene
  • nordihydroguaiaretic acid The antioxidant may comprise roughly 0.02 to about 1.0 weight percent, or, in another embodiment, roughly 0.05 to about 0.1 percent of the composition.
  • Fragrances are aromatic compounds that can impart an aesthetically pleasing aroma to the sunscreen composition and may also be added.
  • Typical fragrances include aromatic materials extracted from botanical sources (i.e. rose petals, gardenia blossoms, jasmine flowers, etc.), which can be used alone or in any combination to create essential oils.
  • botanical sources i.e. rose petals, gardenia blossoms, jasmine flowers, etc.
  • alcoholic extracts may be prepared for compounding fragrances.
  • the fragrance may be added, in one embodiment, to the composition in an amount ranging from about 0.01 to about 5.0 weight percent, or in another embodiment, from about 0.1 to about 2.0 percent.
  • lipophilic skin-moisturizing agents are included in the compositions herein in an amount ranging from about 0.1% to about 30%, or, in another embodiment from about 1% to about 30%, or, in another embodiment from about 3% to about 25%, or, in another embodiment from about 5% to about 25% of the composition.
  • the lipophilic skin-conditioning agent is a hydrocarbon oil or wax, silicone, fatty acid derivative, cholesterol, cholesterol derivative, di- or tri-glyceride, vegetable oil, vegetable oil derivative, liquid nondigestible oil such as those described in U.S.
  • hydrocarbon oils or waxes may also be added to the compositions of the present invention.
  • Some examples are petrolatum, mineral oil microcrystalline waxes, poryalkenes (e.g. hydrogenated and nonhydrogenated polybutene and polydecene), paraffins, cerasin, ozokerite, polyethylene and perhydrosqualene, all of which represent embodiments of this invention.
  • Blends of petrolatum and hydrogenated and/or nonhydrogenated high molecular weight polybutenes wherein the ratio of petrolatum to polybutene ranges from about 90: 10 to about 40:60 are also suitable for use as the lipid skin-moisturizing agent in the compositions herein.
  • the composition further comprises an antihistamine.
  • the antihistamine is diphenhydramine, tripelenamme or cimetidine.
  • the antihistamine is spent grain wax.
  • the antihistamine is a combination thereof.
  • the antihistamine is at a concentration of from roughly 0.0005 % to about 2 %.
  • the antihistamine concentration is from about 0.001 % and 1 %, or in another embodiment, from about 0.001 % to about 0.2%.
  • the compositions may comprise a glycosaminoglycan (GAG).
  • GAGs are long linear polysaccharides consisting of disaccharide repeats that contain an amino sugar and are found in multiple organisms, including jellyfish.
  • incorporation of a GAG within a composition of this invention inhibits nematocyst or polar capsule discharge via acting as a structural mimic for the cnidaria.
  • the GAG is sodium alginate.
  • the GAG is a chondroitin sulfate, a keratin sulfate, a galactosamine or glucosamine, or a molecule homologous thereto, which in another embodiment, assumes a three-dimensional structure similar thereto.
  • each of the additives listed herein may be provided singly, or in another embodiment, in combination to the compositions of this invention. Inclusion of the additives may be, in one embodiment, within the high salt in water in oil emulsion, or in another embodiment, within a composition comprising the same, or in another embodiment, be added during the reformulation of the compositions of this invention to comprise lower concentrations of salts.
  • Ointments containing varied inorganic salt concentration were prepared according to the following protocol, with phases as delineated in Table 1 below.
  • the components of Phase A were solubilized, heated to 60 °C, at which point Phase B was added, and stirred until solubilized. The temperature was then raised to 85 °C, at which point Phase C was subsequently added.
  • Phase D was melted at 85 °C, in a separate container, and while the solution was slowly stirred, phase ABC was added to phase D. The resulting emulsion was then homogenized.
  • Example 2 The High Salt in Water in Oil Emulsion Can Be Reformulated to Comprise the Oil Phase of a Water in Oil Emulsion
  • the high salt in water in oil emulsion was prepared as in Example 1.
  • the high salt in water in oil emulsion was incorporated into the oil phase of a water in oil emulsion containing a sunscreen, as outlined in Table 2.
  • the components of Phase A were combined and heated to 85 °C, at which point Phase A was cooled to 60 °C.
  • the cooled Phase A was slowly stirred, while the components of Phase B were added, and the emulsion was then further cooled to 40 °C, at which point the emulsion was homogenized. Following homogenization, Phase C was added.
  • the high salt in water in oil emulsion was incorporated into the oil phase, phase A, of the sunscreen water in oil emulsion, indicating that the high salt water in oil emulsion can be effectively incorporated into the oil phase of another water in oil emulsion.
  • the high salt in water in oil emulsion was combined in the oil phase of a water in oil emulsion, to form a composition containing a sunscreen for topical administration, further containing the high salt in water in oil emulsion.
  • the sunscreen may be physical filters like Zinc and Titanum or Organic filters like Ethylhexyl Methoxycinnamate or other sunscreen organic filters.
  • Example 3 Compositons Comprising a High Salt in Water in Oil Emulsion and Additional Water in Oil Emulsions
  • the high salt in water in oil emulsion was prepared as in Example 1.
  • the high salt in water in oil emulsion was incorporated into a composition comprising a water in oil emulsion containing a sunscreen, as outlined in Table 3.
  • the components of Phase A were combined and heated to 85 °C, at which point Phase A was cooled to 60 °C.
  • Phase B was then added under slow stirring conditions, and the emulsion was then cooled to 40 °C.
  • Phase C containing the high salt in water in oil emulsion was then added, under slow stirring conditions, and the composition comprising both emulsions was then homogenized, following which phase D was added, while stirred.
  • the high salt in water in oil emulsion can be reformulated to further comprise a sunscreen, where in this case, the high salt in water in oil emulsion is combined during the emulsion phase, and the addition did not influence the homogeneity or the stability of the final formula.
  • Table 3 :
  • Example 4 Compositions Comprising a High Salt in Water in Oil Emulsion are Water-Proof Materials and Methods
  • Example 1 Two grams of the high salt in water in oil emulsion of Example 1 was applied to each of five 4 x 4 inch pieces of fabric squares or cotton balls. An additional five pieces were similarly treated with high salt in water in oil emulsion comprising a sunscreen, of Example 2. One untreated piece served as a control. The other pieces were put separately in 150 ml seawater baths and were violently agitated (200 round / minutes). Every 30 minutes, one piece was taken out. At the end of the experiment, remaining lotion/emulsion was extracted in 40 ml Triton X-100.
  • compositions comprising a high salt water in oil emulsion and sunscreen was also waterproof (Figure 1). At time 0, 100% of cations were present, as above, with after 60 minutes, a loss of about 5-10% and after 120 minutes, a loss of about 25-30 % of the cations, results that indicate that such formulations are water-proof, as well.
  • Example 5 Protection from Nematocyst Discharge in Skin Treated with Compositions Comprising a High Salt in Water in Oil Emulsion Materials and Methods An inner arm of a human subject was marked and divided into 4 grids for conducting 8 independent experiments on each subject. Two grids on each arm were used as a control, and were administered a composition comprising a sunscreen, indicating unprotected skin. The remainder of the grids were treated with a composition comprising a sunscreen and a waterproof high salt in water in oil emulsion. Grid sizes were in the range of 25 square centimeters and the respective compositions was applied onto each grid, for 10-15 minutes prior to exposure to sea water.

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Abstract

La présente invention concerne des émulsions eau dans huile à haute teneur en sel, qui inhibent efficacement la décharge de nématocytes ou de capsules polaires et, un processus de préparation de cette composition. Ces compositions sont aussi efficaces pour inhiber la décharge de nématocytes ou de capsules polaires lorsqu'elles sont repréparées dans ces compositions pour des applications topiques avant l'exposition aux nématocytes.
PCT/IL2005/000169 2004-02-17 2005-02-10 Compositions a haute teneur en sel, procedes de production et d'utilisation de ces compositions WO2005076731A2 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2363135A1 (fr) 2010-03-01 2011-09-07 Antonio Puig, S.A. Compositions contre les méduses
EP2380577A1 (fr) 2010-04-21 2011-10-26 Antonio Puig, S.A. Combinaisons contre les méduses
US10172883B2 (en) 2014-06-10 2019-01-08 Alatalab Solution, Llc Methods and compositions for treating and/or inhibiting toxins using copper-containing compounds

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5188823A (en) * 1991-02-07 1993-02-23 Stepan Company Antiperspirant formulations
US20020198328A1 (en) * 2001-05-16 2002-12-26 L'oreal Water-soluble polymers with a water-soluble backbone and side units with a lower critical solution temperature, process for preparing them, aqueous compositions containing them and cosmetic use thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5188823A (en) * 1991-02-07 1993-02-23 Stepan Company Antiperspirant formulations
US20020198328A1 (en) * 2001-05-16 2002-12-26 L'oreal Water-soluble polymers with a water-soluble backbone and side units with a lower critical solution temperature, process for preparing them, aqueous compositions containing them and cosmetic use thereof

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2363135A1 (fr) 2010-03-01 2011-09-07 Antonio Puig, S.A. Compositions contre les méduses
EP2380577A1 (fr) 2010-04-21 2011-10-26 Antonio Puig, S.A. Combinaisons contre les méduses
US10172883B2 (en) 2014-06-10 2019-01-08 Alatalab Solution, Llc Methods and compositions for treating and/or inhibiting toxins using copper-containing compounds

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