WO2019195064A1 - Topical compositions incorporating silica fibers - Google Patents

Topical compositions incorporating silica fibers Download PDF

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Publication number
WO2019195064A1
WO2019195064A1 PCT/US2019/024456 US2019024456W WO2019195064A1 WO 2019195064 A1 WO2019195064 A1 WO 2019195064A1 US 2019024456 W US2019024456 W US 2019024456W WO 2019195064 A1 WO2019195064 A1 WO 2019195064A1
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WO
WIPO (PCT)
Prior art keywords
composition
sol
skin
gel
topical
Prior art date
Application number
PCT/US2019/024456
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English (en)
French (fr)
Inventor
Mitch Dellinger
Original Assignee
American Nano, LLC
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 American Nano, LLC filed Critical American Nano, LLC
Priority to CA3095574A priority Critical patent/CA3095574A1/en
Priority to CN201980025783.XA priority patent/CN111989089A/zh
Priority to JP2020553632A priority patent/JP7445979B2/ja
Priority to EP19781320.7A priority patent/EP3773485A4/en
Publication of WO2019195064A1 publication Critical patent/WO2019195064A1/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/02Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0241Containing particulates characterized by their shape and/or structure
    • A61K8/027Fibers; Fibrils
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/25Silicon; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/06Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/16Emollients or protectives, e.g. against radiation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/08Anti-ageing preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/41Particular ingredients further characterized by their size
    • A61K2800/412Microsized, i.e. having sizes between 0.1 and 100 microns
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides

Definitions

  • the present invention relates to topical compositions incorporating silica fibers as an additive.
  • Collagen is a protein that provides the matrix that sustains the body’s structures. It provides integrity, firmness and elasticity to tissues. Loss of collagen results in the wrinkles, lines, and loss of smoothness associated with aging skin.
  • Topical products that improve the integrity of skin, including aging or damaged skin, are of great need. Summary
  • the present invention provides topical compositions that comprise a silica fiber powder or dust (e.g., a collection of fibrous fragments) and a topical carrier.
  • Embodiments of the invention further provide methods for treating aging or damaged skin of a subject.
  • the methods involve application of the compositions to improve skin healing, to prevent or reduce scarring, reduce signs of aging, and/or to reduce pain and/or irritation associated with damaged or diseased skin.
  • the topical composition when applied to skin allows silica fiber dust to be deposited in macroscopic or microscopic breaks in skin.
  • the fiber dust or flakes may act as a collagen mimetic that is not substantially
  • the topical carrier may be in the form of a lotion, ointment, paste, cream, foam, balm, soap, shampoo, or gel, and may include other active agents.
  • the fiber composition is prepared by electrospinning a sol-gel into a silica fiber composition, followed by processing the fiber into a fine powder or dust, and incorporating the powder or dust with the topical carrier.
  • the silica fiber composition is electrospun from a gelatinous material into a lightweight fiber mat.
  • the composition may be prepared by electrospinning a sol-gel, which may be prepared with a silicon alkoxide reagent, such as tetraethyl ortho silicate (TEOS), alcohol solvent, and an acid catalyst.
  • TEOS tetraethyl ortho silicate
  • the sol-gel is produced via ripening of sol under controlled environmental conditions, and/or the properties of the sol or sol-gel during the ripening process are monitored, in order to identify various processing windows during which the electrospinning of the sol-gel may be successfully performed.
  • a“sol” is a colloidal solution that gradually evolves towards the formation of a“gel,” i.e., a diphasic system containing both a liquid phase and solid phase.
  • the term“sol-gel” is used to refer to the gel produced from the sol-gel process that may be electrospun into fibers or a fibrous mat.
  • the composition is non-rigid and has a soft texture similar to that of cotton.
  • the sol-gel is electrospun after a ripening process of at least 2 days, or at least 3 days (e.g., from 2 to 7 days), under the controlled environmental conditions.
  • the controlled environment for ripening the sol may involve controlled conditions in terms of humidity, temperature, and optionally barometric pressure.
  • the humidity may be controlled within the range of about 30% to about 90% or from about 40% to about 80%
  • the temperature may be controlled within the range of from about 50° F to about 90° F.
  • the sol When ripening the sol at a constant humidity in the range of about 50% to 70% or 80% and a temperature of about 60 to 80° F, the sol will ripen (gelatinize) in a few days, and the window for successful electrospinning may be expanded to at least several hours, and in some embodiments several days.
  • the sol may therefore be ripened in an enclosure which may include one or more environmental monitors, such as a temperature reading device and/or a humidity reading device. Further, gases produced or released by the sol during the ripening process and/or relative weight of the sol may be monitored to determine a suitable or optimal time for electrospinning.
  • the sol is electrospun to form a mat of entangled silica fibers.
  • the silica fibers may have a variable diameter, such as in the range of from about 50 nm to 5 pm. In some embodiments, the fibers are predominately in the range of about 100 nm to about 2 pm, or predominately in the range of about 200 to about 1000 nm.
  • the silica-fiber mat is successfully formed, it is, in various embodiments, divided into small fibrous fragments that are utilized as an additive in any of a variety of different topical compositions.
  • the electrospun mat may be“fragmented,” i.e., fractured, cut, ground, milled, or otherwise divided into small fragments that maintain a fibrous structure.
  • the term“fibrous fragments” refers to small particles, parts, or flakes of a fibrous mat having an average dimension larger (e.g., 5 c , lOx, or even 100 c ) than the width of at least some of the fibers of the mat.
  • the average size of a fibrous fragment is in the range of approximately 20 pm to approximately 200 pm.
  • Fibrous fragments may thus resemble microscopic-scale versions of the electrospun mat itself, e.g., intertwined collections of silica fibers, and thus typically are porous and have low densities.
  • fibrous fragments may be contrasted with other types of micro-scale particles, such as the substantially spherical particles used in colloidal silica, which are each unitary, individual units or grains, rather than small collections of fibers.
  • Various portions of a fibrous fragment e.g., the edges
  • the term“fiber dust” includes collections of particles generated via the fragmentation of electrospun fiber mats and/or fibers, and may include fibrous fragments and/or other powder particles resulting from such fragmentation.
  • Embodiments of the present invention may employ silica fibers, fragments thereof, and/or compositions incorporating such fibers or fragments, and/or methods for fabricating such fibers or fragments detailed in U.S. Patent Application Serial No. 15/934,599, filed on March 23, 2018 (issued as U.S. 10,111,783), and U.S. Patent Application Serial No. 16/131,531, filed on September 14, 2018, the entire disclosure of each of which is incorporated by reference herein.
  • the fiber dust or fibrous fragments are incorporated with a topical carrier.
  • the topical composition may be a skin care composition or a cosmetic composition.
  • the fiber dust or fragments are distributed in a carrier system such as water or any aqueous solution containing organic or inorganic materials.
  • the compositions may contain one or more ingredients to modify or enhance their texture, appearance, scent performance or stability.
  • Illustrative additives to the compositions include: oily components, fatty components, ointment bases, hydrophilic solvents, lipophilic solvents, emollients, water, buffering agents, pH-adjusting agents, preservatives, humectants, chelating agents, antioxidants, stabilizers, emulsifying agents, suspending agents, gel-forming agents, perfumes and fragrances, skin protective agents, and antiseptics.
  • the composition further comprises one or more anti inflammatory agents such as steroidal anti-inflammatory agents or non-steroidal anti inflammatory agents (NSAIDs).
  • the composition further comprises one or more antimicrobial agents.
  • the composition further comprises one or more pain reducing agents.
  • the invention provides a method for treating skin tissue in a subject, which comprises applying the topical composition to skin tissue.
  • the composition can be used routinely or periodically.
  • the composition is applied at least about daily.
  • the method improves healing of the skin tissue and/or prevents or reduces tissue scarring, looseness of skin, age spots, pain, and/or irritation.
  • composition can provide for improved or accelerated healing of damaged skin.
  • topical composition when the topical composition is applied to skin that has cracks, small scrapes, blemishes, etc., the scaffolding is left behind in the small“wound” for cells to grow into. This speeds up the healing process and helps to reduce scarring.
  • the composition is applied to cracked skin, which can improve tolerance of the skin to the environment, such as sun, wind, and cold.
  • the composition is applied to a skin lesion, superficial wound or infection, acne, bum, ulcer, cut, scrape, rash, blister, allergic reaction, hives, or insect or spider bites or stings.
  • exemplary conditions include aging skin, dry skin, eczema, pruritus, sun bum, reaction to poison ivy or poison oak, post-surgery wound, skin graft, mosquito bites, and genetic diseases that impact skin integrity (such as but not limited to epidermolysis bullosa and ichthyosis).
  • the composition is applied to diseased skin, which can be a manifestation of a
  • the composition is applied to a microbial infection of the skin.
  • the composition is applied to skin affected by shingles, providing, for example, relief from associated pain.
  • Other conditions that may benefit from the pain reducing properties of the invention include neuropathy, joint pain, and gout.
  • embodiments of the invention feature a topical composition
  • a topical composition comprising, consisting essentially of, or consisting of a silica fiber powder or dust, and a topical carrier.
  • Embodiments of the invention may include one or more of the following in any of a variety of combinations.
  • the topical carrier may be a lotion, ointment, balm, paste, cream, foam, soap, shampoo, bath salt, and/or gel.
  • the composition may further include one or more pharmaceutical or antimicrobial agents.
  • the composition may further include an antibiotic and/or antiseptic.
  • the composition may further include an anti-inflammatory agent, immunosuppressant, and/or pain-reducing agent.
  • the composition may further include an anti-fibrotic and/or anti-scarring agent.
  • the composition may be prepared by electrospinning a sol-gel into a silica fiber composition, processing the silica fiber composition into powder or dust, and incorporating the powder or dust with the topical carrier.
  • the sol-gel may be prepared with tetraethyl orthosilicate (TEOS).
  • TEOS tetraethyl orthosilicate
  • the sol-gel Prior to electrospinning the sol-gel, the sol-gel may be produced from an initial sol comprising, consisting essentially of, or consisting of 70% to 90% TEOS by weight, 8% to 25% ethanol by weight, an acid catalyst, and water.
  • the initial sol may comprise, consist essentially of, or consist of 70% to 90% TEOS by weight, 8% to 25% ethanol by weight, an acid catalyst, and water.
  • the initial sol may contain 70% to 90% TEOS by weight, 8% to 25% ethanol by weight, an acid catalyst, and the balance water.
  • the initial sol may comprise, consist essentially of, or consist of 70% to 90% TEOS by weight, 8% to 25% ethanol by weight, an acid catalyst, and water.
  • the initial sol may contain 70% to 90% TEOS by weight, 8% to 25% ethanol by weight, an acid catalyst, and the balance water.
  • the initial sol may comprise, consist essentially of, or consist of 70% to 90% TEOS by weight, 8% to 25% ethanol by weight, an acid catalyst, and water.
  • the initial sol may comprise, consist essentially of, or consist of 70% to 90% TEOS by weight, 8% to 25% ethanol by weight, 1% to 10% water by weight, and the acid catalyst.
  • the initial sol may comprise, consist essentially of, or consist of 75% to 85% by weight TEOS, 12% to 20% by weight ethanol, and about 2% to 5% by weight water.
  • the initial sol may comprise, consist essentially of, or consist of about 80% by weight TEOS, about 17% by weight ethanol, and about 3% by weight water.
  • the acid catalyst may comprise, consist essentially of, or consist of HC1.
  • the initial sol may contain less than about 0.1% of the acid catalyst by weight.
  • the initial sol may contain from 0.02% to 0.08% of the acid catalyst by weight.
  • the initial sol may contain one or more reagents that alter one or more properties of the initial sol, the sol-gel, and/or the silica fibers.
  • Producing the sol-gel may include transitioning the initial sol for at least 2 days under conditions where humidity is within the range of about 40% to about 80%, and the temperature is within the range of 50° F to 90° F.
  • the initial sol may be allowed to transition for at least 3 days, at least 4 days, at least 5 days, at least 6 days, or at least 7 days.
  • the initial sol may be allowed to transition for 2 days to 10 days, and for 2 days to 7 days in some embodiments.
  • the sol-gel may be electrospun when the weight is at from 20% to 40% of the starting weight of the initial sol or sol-gel before ripening (transitioning).
  • the sol-gel may be electrospun when the production of ethylene vapor is 10% to 20% relative to the peak production of ethylene vapors during ripening (transitioning) of the initial sol or sol-gel before ripening.
  • the sol-gel may be electrospun when the production of ethylene vapor therefrom is 10% to 40% relative to the initial sol or sol-gel before ripening (transitioning).
  • the powder or dust may comprise, consist essentially of, or consist of particles and/or fibrous fragments that may have an average size (e.g., average diameter, length, width, or other dimension) ranging from approximately 20 pm to approximately 200 pm.
  • the fibers may have a variable diameter of from about 50 nm to about 5 pm.
  • the fibers may have a variable diameter of from about 200 nm to about 1000 nm.
  • the silica fiber powder or dust may consist essentially of or consist of SiC .
  • embodiments of the invention feature a method for treating skin tissue in a subject.
  • the method may comprise, consist essentially of, or consist of applying a topical composition to said skin tissue.
  • the topical composition comprises, consists essentially of, or consists of a silica fiber powder or dust, and a topical carrier.
  • the topical composition may comprise, consist essentially of, or consist of any topical composition described herein.
  • Embodiments of the invention may include one or more of the following in any of a variety of combinations.
  • the method may improve healing of the skin tissue and/or prevent or reduce tissue scarring, pain, and/or irritation.
  • the subject may be a mammal.
  • the subject may be a veterinary patient, such as a dog, cat, or horse.
  • the subject may be a human patient.
  • the composition may be applied to a skin lesion, scar, superficial wound or infection, bum, cut, scrape, rash, blister, bug bite, poison ivy or poison oak, and/or hives.
  • the subject may have a genetic disease of the skin, e.g., epidermolysis bullosa or ichthyosis.
  • the subject may have a first, second, or third degree bum, or combination thereof.
  • the composition may be applied to a sun bum.
  • the composition may be applied to a melanoma lesion.
  • the composition may be applied to aging skin, age spots, dry skin, cracked skin, and/or scar tissue.
  • the composition may be applied to skin affected by eczema and/or atopic dermatitis.
  • the composition may be applied to skin affected by psoriasis.
  • the composition may be applied to skin affected by acne and/or rosacea.
  • the composition may be applied to a post-surgery wound and/or sutures (e.g., sutures utilized to at least partially close a wound).
  • the composition may be applied to skin affected by pruritus.
  • the composition may be applied to skin affected by shingles and/or lupus.
  • the subject may be affected by neuropathy, joint pain, and/or gout.
  • the composition may be applied to skin impacted by dermatitis herpetiformis and/or dermatomyositis.
  • the composition may be applied to skin showing signs of microbial infection and/or skin infected by one or more microbes, such as a virus, bacteria, or fungus.
  • the microbial infection may be HPV, herpes simplex virus, varicella-zoster virus, fungal infection, and/or staphylococcus infection.
  • the composition may be applied as a bath including the silica fiber powder or dust (e.g., the topical carrier may include, consist essentially of, or consist of water and/or another bathing fluid).
  • FIGS. 1A-1D are scanning electron microscopy (SEM) images of fibers spun in accordance with embodiments of the invention. Images in FIGS. 1 A-1D are at, respectively, 50, 100, 200, and 500 micron scale. As shown, the fibers are flexible, smooth, dense, and continuous (not fractured).
  • FIG. 2 shows an SEM image (20 micron scale is shown) of fibers spun at a non-optimal time. The fibers are rigid, with fractures clearly evident.
  • FIG. 3 shows a fiber mat spun with a thickness of about 1/4 inch in accordance with embodiments of the invention.
  • the mat has a soft, flexible texture.
  • FIGS. 4A and 4B compare a silica fiber mat that was electrospun when the sol-gel was transitioned in accordance with certain embodiments of the invention (FIG. 4A), with a fiber mat that was spun early, before the sol-gel was optimally ripened (FIG. 4B).
  • FIGS. 5 A and 5B show SEM images of fiber dust in accordance with embodiments of the invention, with 100 pm scale shown.
  • FIGS. 6A and 6B show a shingles rash prior to treatment with a silica fiber topical composition in accordance with embodiments of the invention (FIG. 6A) and the rash after of about 1.5 days with frequent application in accordance with embodiments of the invention (FIG. 6B).
  • FIG. 7A shows a bum prior to treatment with a silica fiber topical composition in accordance with embodiments of the invention.
  • FIG. 7B shows the bum of FIG. 7A after of about 4 days of frequent application with a silica fiber topical composition in accordance with embodiments of the invention.
  • Embodiments of the present invention provide topical compositions that comprise a silica fiber powder or dust, and a topical carrier.
  • the invention provides methods for treating aging or damaged skin of a subject.
  • the methods involve application of the compositions to improve skin healing, to prevent or reduce scarring, reduce signs of aging, or to reduce pain or irritation associated with damaged skin.
  • the compositions improve the look and appearance of skin.
  • the topical composition when applied to skin allows silica fiber dust to be deposited in macroscopic or microscopic breaks in skin.
  • the fiber dust or flakes act as a collagen mimetic that is not substantially biodegradable, and which may promote cell infiltration and/or collagen deposition, and in some embodiments reduces local production of pain and/or inflammatory mediators.
  • the fiber dust is incorporated with a topical carrier, which may be in the form of a lotion, ointment, balm, paste, cream, foam, soap, shampoo, or gel, and may comprise other active agents.
  • a topical carrier which may be in the form of a lotion, ointment, balm, paste, cream, foam, soap, shampoo, or gel, and may comprise other active agents.
  • the fiber composition is prepared by electrospinning a sol-gel into a silica fiber composition, followed by processing the fiber into a fine powder or dust, and incorporating the powder or dust with the topical carrier.
  • the silica fiber composition is electrospun from a gelatinous material into a lightweight fiber mat.
  • the composition may be prepared by electrospinning a sol-gel, which can be prepared with a silicon alkoxide reagent, such as tetraethyl ortho silicate (TEOS), alcohol solvent, and an acid catalyst.
  • a silicon alkoxide reagent such as tetraethyl ortho silicate (TEOS), alcohol solvent, and an acid catalyst.
  • Known processes for electrospinning silica fibers do not yield a fiber composition with sufficient flexibility and texture suitable or ideal for topical compositions. Instead, these structures are comparatively brittle, rigid, and compact; and fiber mats are thin and will easily fracture. Generally, these materials lack the physical characteristics to mimic collagen deposition.
  • the composition is non- rigid and has a soft texture similar to that of cotton.
  • the silica fiber composition when applied to wounded tissue, acts as a non-biodegradable scaffold that supports tissue healing, regeneration, and/or integrity.
  • the composition acts as a collagen biomimetic at the site of damaged tissue, providing an environment conducive for regeneration and growth of dermal cells and/or natural deposition of collagen.
  • compositions and methods described herein limit pain and inflammation at the site of damaged tissue. Further, uncontrolled tissue degradation processes can destroy newly deposited collagen.
  • the composition of the invention provides a non-biodegradable scaffold that is not destroyed by proteases released at the site of tissue injury, but provides an optimal environment for population and growth of dermal cells. The fibers will become an integral part of the regenerating tissue.
  • the fibers may have a variable or more uniform diameter, such as in the range of from about 50 nm to 5 pm. In some embodiments, the fibers are predominately in the range of about 100 nm to about 2 pm, or predominately in the range of about 200 to about 1000 nm.
  • the size(s) of the fibers is a better mimic for natural collagen, compared to, for example, brittle scaffolding including those intended to have a more uniform structure.
  • the sol-gel for preparing the silica fiber composition is prepared by a method that includes preparing a first mixture containing an alcohol solvent, a silicon alkoxide reagent such as tetraethylorthosilicate (TEOS); preparing a second mixture containing an alcohol solvent, water, and an acid catalyst; fully titrating the second mixture into the first mixture; and processing (ripening) the combined mixture to form a gel for electrospinning.
  • TEOS tetraethylorthosilicate
  • the silicon alkoxide reagent is TEOS.
  • Alternative silicon alkoxide reagents include those with the formula Si(OR)4, where R is from 1 to 6, and preferably 1, 2, or 3.
  • the sol comprises, consists essentially of, or consists of about 70% to about 90% by weight silicon alkoxide (e.g., TEOS), about 5% to about 25% by weight alcohol solvent (e.g., anhydrous ethanol), an acid catalyst (e.g., less than about 0.1% by weight when using HC1) and water.
  • silicon alkoxide e.g., TEOS
  • alcohol solvent e.g., anhydrous ethanol
  • an acid catalyst e.g., less than about 0.1% by weight when using HC1
  • Any sol or sol-gel described herein may include the balance water (i.e., water may constitute any amount of the sol or sol-gel that is otherwise unspecified).
  • Any sol or sol-gel described herein may optionally contain one or more reagents that may or do alter one or more properties of the sol, the sol-gel, and/or the silica fibers.
  • Such reagents may include, but are not limited to, for example, polymers and polymeric solutions, inert reagents, alcohols, organic and/or aqueous solvents, organic salts, inorganic salts, metals, metal oxides, metal nitrides, metal oxynitrides, carbon (e.g., graphene, graphite, fullerenes, etc.), etc.
  • the sol contains 70% to 90% tetraethyl orthosilicate (TEOS) by weight, 8% to 25% ethanol by weight, 1% to 10% water by weight, and an acid catalyst.
  • the sol contains 75% to 85% by weight TEOS, 12% to 20% by weight ethanol, and about 2% to 5% by weight water.
  • An exemplary sol contains about 80% by weight TEOS, about 17% by weight ethanol, and about 3% by weight water.
  • the acid catalyst is HC1.
  • the sol may contain less than about 0.1% HC1 by weight.
  • the sol may contain from 0.02% to 0.08% HC1 by weight.
  • the sol does not contain an organic polymer, or other substantial reagents, such that the fiber composition will be substantially pure SiCh.
  • the sol does not include inorganic salts (e.g., sodium chloride, lithium chloride, potassium chloride, magnesium chloride, calcium chloride, and/or barium chloride), nor are, in various embodiments, inorganic salts mixed with other components of the sol or into the sol itself.
  • the fiber composition does not include metals or metal oxides (e.g., TiCh or ZrCh).
  • the fiber composition consists essentially of SiCh, i.e., contains only SiCh and unintentional impurities, and, in some embodiments, species and/or complexes resulting from the incomplete conversion of the sol to SiC (e.g., water and/or chemical groups such as ethoxy groups, silanol groups, hydroxyl groups, etc.) ⁇
  • the alcohol solvent is an anhydrous denatured ethanol, or in some embodiments, methanol, propanol, butanol or any other suitable alcohol solvent.
  • the first mixture may be agitated, for example, using a magnetic stirrer, vibration platform or table, or other agitation means.
  • the second mixture contains an alcohol solvent, water, and an acid catalyst.
  • the alcohol solvent may be an anhydrous denatured alcohol, or may be methanol, propanol, butanol or any other suitably provided alcohol solvent.
  • Water may be distilled water or deionized water.
  • Enough acid catalyst is added to the mixture to aid in the reaction. This acid catalyst may be hydrochloric acid, or may be sulfuric acid or other suitable acid catalyst.
  • the second mixture may be agitated, for example, magnetic stirrer, vibration platform or table, or other agitation means.
  • the first mixture (or sol) and the second mixture (or sol) are created without the use of direct heat (i.e., heat applied via extrinsic means such as a hot plate or other heat source).
  • the first mixture and the second mixture are combined by dripping or titrating the second mixture into the first mixture, preferably with agitation.
  • the combined mixture is then further processed by allowing the sol to ripen in a controlled environment until a substantial portion of the alcohol solvent has evaporated to create a sol-gel suitable for electrospinning.
  • the controlled environment may include an enclosure with at least one vent and optionally a fan to draw gases away from the mixture, and which may involve controlled conditions in terms of humidity, temperature, and optionally barometric pressure.
  • the humidity may be controlled (e.g., via use of conventional humidifiers and/or dehumidifiers) within the range of about 30% to about 90%, such as from about 40% to about 80%, or in some embodiments, from about 50% to about 80%, or from about 50% to about 70% (e.g., about 55%, or about 60%, or about 65%). Some humidity may be helpful to slow evaporation of solvent, and thereby lengthen the window for successful electrospinning.
  • the temperature is in the range of from about 50° F to about 90° F, such as from about 60° F to about 80° F, or from about 65° F to about 75° F.
  • the sol is not exposed to heat over 150° F or heat over 100° F, so as to avoid accelerating the transition.
  • barometric pressure is optionally controlled (e.g., using a low pressure vacuum source such as a pump or a fan).
  • a low pressure vacuum source such as a pump or a fan.
  • the sol When ripening the sol at a constant humidity of about 55% and temperature of about 72° F, the sol will ripen (gelatinize) in a few days, and the window for successful electrospinning may be expanded to at least several hours, and in some embodiments several days.
  • the ripening process takes at least 2 days, or at least 3 days in some embodiments. However, in various embodiments the ripening does not take more than 10 days, or more than 7 days. In some embodiments, the ripening process takes from 2 to 10 days, or from 2 to 7 days, or from 2 to 5 days, or from 2 to 4 days (e.g., about 2, about 3, or about 4 days).
  • the sol-gel is spinnable well before it transitions into a more solidified, non-flowable mass.
  • the enclosure space for ripening the sol-gel may include a vent on at least one surface for exhausting gases from within the enclosure, and optionally the vent may include a fan for exhausting gases produced during the ripening process.
  • the enclosure space may optionally include a heating source (e.g., one or more heating elements, for example resistive heating elements) for providing a nominal amount of heat within the enclosure space, to maintain a preferred temperature.
  • a source of humidity e.g., an open container of water or other aqueous, water-based liquid is provided within the enclosure environment to adjust the humidity to a desired range or value.
  • the enclosure may further include one or more environmental monitors, such as a temperature reading device (e.g., a thermometer, thermocouple, or other temperature sensor) and/or a humidity reading device (e.g., a hygrometer or other humidity sensor).
  • a temperature reading device e.g., a thermometer, thermocouple, or other temperature sensor
  • a humidity reading device e.g., a hygrometer or other humidity sensor
  • the sol-gel is electrospun after a ripening process of at least 2 days, or at least 36 hours, or at least 3 days, or at least 4 days, or at least 5 days at the controlled environmental conditions (but in various embodiments, not more than 10 days or not more than 7 days under the controlled environmental conditions).
  • a ripening process of at least 2 days, or at least 36 hours, or at least 3 days, or at least 4 days, or at least 5 days at the controlled environmental conditions (but in various embodiments, not more than 10 days or not more than 7 days under the controlled environmental conditions).
  • the weight of the sol-gel may be used as an indicator of when the sol-gel is at or near the ideal time to electrospin. Without intending to be bound by theory, it is believed that the viscosity of the sol-gel is a poor determinant for identifying the optimal time for electrospinning.
  • the sol-gel is from about 10% to about 60% of the original weight of the sol (based on loss of alcohol solvent during transitioning). In some embodiments, the sol-gel is from 15 to 50% of the original weight of the sol, or in the range of about 20 to about 40% of the original weight of the sol.
  • the sol-gel is ripened for at least 2 days, or at least 36 hours, or at least 3 days, or at least 4 days, or at least 5 days, and is electrospun when the ethylene vapors produced by the composition are between about 10% and about 40% of the vapors produced by the starting sol, such as in the range of about 10% and about 25%, or in the range of about 10% to about 20%.
  • Ethylene is a colorless flammable gas with a faint sweet and musky odor (which is clearly evident as solvent evaporation slows). Ethylene is produced by the reaction of ethanol and acid.
  • Ethylene may optionally be monitored in the vapors using a conventional ethylene monitor.
  • gases produced by the sol during the sol ripening process are monitored to determine a suitable or optimal time for electrospinning.
  • Gas profiles may be monitored using gas chromatography.
  • the sol-gel may be ripened for a shorter period of time, as long as the sol-gel remains spinnable via electrospinning.
  • the resulting silica fiber mat or collection of fibers may in some cases be more brittle after ripening for a shorter time period, but such brittleness may not prevent the fragmenting of the fibers and dispersion into various different topical compositions.
  • the processing of the sol-gel mixture may require stirring or other agitation of the mixtures at various intervals or continuously due to the development of silicone dioxide crystalline material on the top surface of the mixtures. This development of crystalline material on the top surface slows the processing time and it is believed that the crystalline material seals off exposure of the mixture to the gaseous vacuum provided within the enclosure space. In some embodiments, any solid crystalline material is removed from the mixture.
  • the sol-gel Upon completion of the sol-gel process, the sol-gel is then electrospun using any known technique.
  • the sol or sol-gel may be preserved (e.g., frozen or refrigerated) if needed (and such time generally will not apply to the time for ripening).
  • An exemplary process for electrospinning the sol-gel is described in Choi, Sung-Seen, et al, Silica nanofibers from electrospinning/sol-gel process. Journal of Materials Science Letters 22, 2003, 891-893, which is hereby incorporated by reference in its entirety. Exemplary processes for electrospinning are further disclosed in U.S. Patent No. 8,088,965, which is hereby incorporated by reference in its entirety.
  • the sol-gel is placed into one or more syringe pumps that are fluidly coupled to one or more spinnerets.
  • the spinnerets are connected to a high-voltage (e.g., 5 kV to 50 kV) source and are external to and face toward a grounded collector drum.
  • the drum rotates during spinning, typically along an axis of rotation approximately perpendicular to the spinning direction extending from the spinnerets to the drum.
  • the sol-gel is supplied to the spinnerets from the syringe pumps (or other holding tank), the high voltage between the spinnerets and the drum forms charged liquid jets that are deposited on the drum as small entangled fibers.
  • a fibrous mat of silica fibers is formed around the circumference of the drum.
  • the spinnerets and syringe pump(s) may be disposed on a movable platform that is movable parallel to the length of the drum. In this manner, the length along the drum of the resulting fiber mat may be increased without increasing the number of spinnerets.
  • the diameter of the drum may also be increased to increase the areal size of the electrospun mat.
  • the thickness of the mat may be largely dependent upon the amount of sol-gel used for spinning and thus the amount of electrospinning time. For example, the mat may have a thickness of greater than about 1/8 inch, or greater than about 1/4 inch, or greater than about 1/3 inch, or greater than about 1/2 inch.
  • the resulting mat is removed from the drum.
  • the mat may be cut and peeled away from the drum in one or more pieces.
  • the mat may then be divided into small fibrous fragments that may be incorporated into the topical composition.
  • the resulting fibrous fragments are each intertwined collections of silica fibers, rather than unitary solid particles.
  • the electrospun mat may be fractured, cut, ground, milled, or otherwise divided into small fragments that maintain a fibrous structure.
  • the mat (or one or more portions thereof) is rubbed through one or more screens or sieves, and the mesh size of the screen determines, at least in part, the size of the resulting fibrous fragments or powder or dust produced from the electrospun mat.
  • the mat or mat portions may be rubbed through a succession of two or more screens having decreasing mesh sizes (e.g., screens having mesh numbers of 100, 200, 300, or even 400), in order to produce a powder or dust or collection of fibrous fragments having the desired sizes.
  • the fiber dust or fibrous fragments are incorporated with a topical carrier, which can be in the form of a lotion, ointment, balm, paste, cream, foam, soap, shampoo, conditioner, or gel.
  • the topical composition can be a skin care composition or a cosmetic composition.
  • the fiber dust or fragments are distributed in a carrier system such as water or any aqueous solution containing organic or inorganic materials.
  • the compositions may contain one or more ingredients to modify or enhance their texture, appearance, scent performance or stability.
  • Illustrative additives to the compositions include: oily components, fatty components, ointment bases, hydrophilic solvents, lipophilic solvents, emollients, water, buffering agents, pH-adjusting agents, preservatives, humectants, chelating agents, antioxidants, stabilizers, emulsifying agents, detergents, suspending agents, gel-forming agents, perfumes and fragrances, skin protective agents, and antiseptics.
  • the fiber dust or fibrous fragments are incorporated into the composition at from about 5 mg/ml to about 500 mg/ml, or from about 5 mg/ml to about 400 mg/ml, or from about 5 mg/ml to about 250 mg/ml. In some embodiments, the dust or fiber fragments are incorporated into the composition at from about 10 mg/ml to about 200 mg/ml, or from about 10 mg/ml to about 150 mg/ml, or from about 25 mg/ml to about 100 mg/ml.
  • the topical composition may comprise oily or fatty components, which are constituents of the hydrophobic phase, and can include one or more of: almond oil, castor oil, cacao butter, coconut oil, com oil, cottonseed oil, linseed oil, olive oil, palm oil, peanut oil, poppy seed oil, rapeseed oil, sesame oil, soybean oil, sunflower oil, teaseed oil, jojoba oil, mineral oils, silicone oils, fatty oils, liquid paraffin, beeswax, lanolin, white soft paraffin, yellow soft paraffin, petrolatum, triglycerides, cetyl alcohol, stearyl alcohol, isopropyl myristate, oleic acid, isopropyl palmitate, stearic acid, sorbitan esters of fatty acids, sorbitan esters of fatty acids and ethylene oxide (including Tween).
  • oily or fatty components which are constituents of the hydrophobic phase, and can include one or more of: almond oil, castor
  • the topical composition may comprise an aqueous phase, which constitutes the hydrophilic phase and which may comprise water, one or more other hydrophilic solvents, and/or one or more surfactants and/or emulsifier.
  • the aqueous phase may comprise solvents such as water, polyethylene glycol, propylene glycol, glycerol, sorbitol, and alcohols such as ethanol and isopropyl alcohol.
  • the composition may comprise one or more emulsifiers (emulsifying agents), which can be part of the aqueous phase and/or oil phase.
  • emulsifier means an amphiphilic molecule possessing both polar and non-polar regions which are covalently bound and capable of reducing the surface tension of water and for the interfacial tension between water and an immiscible liquid.
  • Emulsifiers include soaps, detergents, surface active agents, and the like.
  • the emulsifier can be cationic, anionic, non-ionic, or amphoteric.
  • Exemplary emulsifiers include non-ionic emulsifiers such as polyol esters (e.g.
  • ethylene glycol diethylene glycol, glycol stearate and propylene glycol monoesters of fatty acids
  • glycerol esters e.g. glyceryl stearate, glyceryl monooleate, glycerylmonolaurate, glyceryl ricinolate, glyceryl monocaprylate.
  • Exemplary emulsifiers further include Sorbitan derivatives, which are esters of cyclic anhydrides of sorbitol with a fatty acid. These include sorbitan monolaurate, sorbitan monooleate, sorbitan monostearate, sorbitan monopalmitate, sorbitan sesquioleate, sorbitan trioleate, sorbitan tristearate, polyoxyethylene sorbitan esters (e.g.
  • polyoxyethylene sorbitan monostearate polyoxyethylene sorbitan tristearate, polyoxyethylene sorbitan monooleate
  • exemplary emulsifiers also include polyoxyethylene esters, which are mixtures of mono- or di-fatty acids esters (from C12 to C18) of polyoxyethylene glycol. These include stearate esters of PEG (PEG- 40, PEG-50 and PEG-55), as well as laurate, oleate, and myristate esters of PEG.
  • the composition can comprise polymeric thickeners including gums such as acacia, alginates, carageenan, chitosan, collagen, tragacanth and xantham; celluloses, acrylic acids, colloidal solids such as silica, clays and microcrystalline cellulose, hydrogels such as polyvinyl alcohol and polyvinylpyrrolidone, as well as
  • thermoreversible polymers such as poloxamers.
  • composition may further comprise one or more pharmaceutical or antimicrobial agents suitable for topical application.
  • exemplary pharmaceutical agents include anti-fibrotic and anti-scarring agents.
  • the composition comprises an antibiotic or antiseptic.
  • Antibiotics suitable for use in the present invention include, but are not limited to, cephalosporin antibiotics, tetracycline antibiotics, beta-lactams, carbapenem antibiotics, polymyxin B (neosporin), neomycin, and bacitracin.
  • Antiseptics include, without limitation, phenol, meta-cresol, methylparaben, and sodium benzoate.
  • the composition further comprises one or more anti inflammatory agents such as steroidal anti-inflammatory agents or non-steroidal anti inflammatory agents (NSAIDs). Steroids, particularly the adrenal corticosteroids and their synthetic analogues, are well known in the art.
  • NSAIDs non-steroidal anti inflammatory agents
  • corticosteroids examples include, without limitation, hydroxyltriamcinolone, alpha-methyl dexamethasone, beta-methyl betamethasone, beclomethasone dipropionate, clobetasol valerate, desonide, desoxymethasone, dexamethasone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, fluclorolone acetonide, flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortine butylester, fluocortolone, fluprednidene
  • fluprednylidene acetate, flurandrenolone, halcinonide, triamcinolone acetonide, cortisone, cortodoxone, flucetonide, fludrocortisone, difluorosone diacetate, fluradrenolone acetonide, medrysone, amcinafel, amcinafide, betamethasone, chloroprednisone, clocortelone, clescinolone, dichlorisone, difluprednate, flucloronide, flunisolide, fluoromethalone, fluperolone, fluprednisolone,
  • the composition comprises at least one active agent for reducing pain, including but not limited to cortisone, hydrocortisone, acetaminophen, or a cannabinoid.
  • the invention provides a method for treating skin tissue in a subject.
  • the method comprises applying the topical composition described herein to skin tissue.
  • the composition can be applied routinely or periodically.
  • the composition is applied at least about daily, and in some embodiments from 1 to about 10 times per day.
  • the method improves healing of the skin tissue and/or prevents or reduces tissue scarring, looseness of skin, signs of aging, pain, and/or irritation.
  • compositions can provide for improved or accelerated healing of damaged skin.
  • topical composition when the topical composition is applied to skin that has cracks, small scrapes, blemishes, etc., the scaffolding is left behind in the small“wound” for cells to grow into. This speeds up the healing process and helps to reduce scarring.
  • the composition in lotion or other form is applied to the cracked skin (e.g., on the face, mouth or lips, neck, hands, arms, shoulders, legs, scalp, fingers, etc.) to improve tolerance of the skin to the cracked skin (e.g., on the face, mouth or lips, neck, hands, arms, shoulders, legs, scalp, fingers, etc.) to improve tolerance of the skin to the cracked skin (e.g., on the face, mouth or lips, neck, hands, arms, shoulders, legs, scalp, fingers, etc.) to improve tolerance of the skin to the cracked skin (e.g., on the face, mouth or lips, neck, hands, arms, shoulders, legs, scalp, fingers, etc.) to improve tolerance of
  • the composition is a lip balm, which can comprise the silica dust suspended in a wax base (e.g., camauba wax, paraffin, and/or beeswax).
  • a wax base e.g., camauba wax, paraffin, and/or beeswax.
  • the lip balm may be an ointment, e.g., comprising petroleum jelly or similar base, including bases described herein.
  • the composition is applied as a soap or shampoo during bathing.
  • the silica composition is a bath salt employed for bathing.
  • the composition is applied to an insect or spider bite or sting, including bee sting, wasp sting, mosquito bite, spider bite, flea bite, fly or ant bites, bits from bed bugs, or others.
  • the composition is applied to skin that has been contacted with or is manifesting a reaction to poison ivy or poison oak.
  • the composition is applied to a skin allergic reaction or hives.
  • the composition in these embodiments may include additional agents to reduce itch or swelling (e.g., corticosteroid or antihistamine), pain (e.g., acetaminophen or NSAID), or allergic responses (e.g., antihistamine).
  • antihistamines include brompheniramine, carbinoxamine maleate, chlorpheniramine, clemastine, diphenhydramine, hydroxyzine triprolidine, cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, and oloptadine.
  • the composition is applied to skin showing signs of microbial infection, including HPV (e.g., wart), herpes simplex virus (e.g., cold sore), varicella-zoster virus (e.g., chicken pox or shingles), fungal infection (e.g., candidiasis or tinea versicolor), or staphylococcus infection or over colonization.
  • HPV e.g., wart
  • herpes simplex virus e.g., cold sore
  • varicella-zoster virus e.g., chicken pox or shingles
  • fungal infection e.g., candidiasis or tinea versicolor
  • staphylococcus infection or over colonization e.g., the composition comprises one or more antibiotics (e.g., antibacterial or anti-fungal agent), antiviral agent, or antiseptic.
  • the subject is a mammal.
  • Subjects include veterinary patients such as a dog, cat, or horse, among others.
  • the patient is a human patient.
  • the patient is a pediatric patient.
  • the composition is applied to a skin lesion, superficial wound or infection (e.g., acne), bum, cut, scrape, rash (e.g., diaper rash), blister (including ruptured blister), or hives.
  • the composition is applied to cracked or scraped skin.
  • the composition is applied to aging skin or dry skin, including eczema, atopic dermatitis, or pruritus.
  • the topical composition normalizes the tissue microenvironment, and may reduce pain and inflammation at the site, and/or provide a microscaffold for dermal cells to multiply and grow into, and in some embodiments induce collagen deposition.
  • the subject has a first, second, or third degree bum, or a combination thereof.
  • the composition is applied to a sun bum, and reduces pain or discomfort.
  • the composition is applied to a post-surgery wound, including skin graft, skin comprising sutures, or cosmetic surgery wound.
  • the composition is applied to age spots (e.g., solar lentigines). Applying the composition routinely (e.g., at least daily) for several days can fade or reduce visible age spots.
  • age spots e.g., solar lentigines.
  • Applying the composition routinely e.g., at least daily for several days can fade or reduce visible age spots.
  • the patient may be able to forgo therapy with a pain medication such as an opioid.
  • the subject has a genetic disease that impacts skin barrier function, such as but not limited to epidermolysis bullosa or ichthyosis.
  • EB Epidermolysis bullosa
  • the subject has epidermolysis bullosa simplex, which results in blisters at the site of rubbing, and typically affects the hands and feet.
  • the subject has junctional epidermolysis bullosa, which affects laminin and collagen. Junctional epidermolysis bullosa also presents with blisters at the site of friction, especially on the hands and feet.
  • Dystrophic epidermolysis bullosa is an inherited variant affecting the skin and other organs, and involves skin that is very fragile. Dystrophic epidermolysis bullosa is caused by genetic defects (or mutations) within the gene encoding the protein type VII collagen (collagen VII).
  • the human skin consists of two layers: an outermost layer called the epidermis and a layer underneath called the dermis. In individuals with healthy skin, there are protein anchors between these two layers that prevent them from moving
  • the subject has ichthyosis.
  • Ichthyosis is a family of genetic skin disorders characterized by dry, thickened, scaly skin. The more than 20 types of ichthyosis range in severity of symptoms, outward appearance, and underlying genetic cause. The severity of symptoms can vary, from the mildest, most common, types such as ichthyosis vulgaris, which may be mistaken for normal dry skin, up to life-threatening conditions such as harlequin-type ichthyosis.
  • the topical composition is applied to a subject having any of the types of ichthyosis, including harlequin ichthyosis.
  • the composition is applied to diseased skin, which can be a manifestation of a proliferative disorder (e.g., carcinoma, pre-carcinoma, or melanoma lesion, or other cancer lesion, or psoriasis), or in some embodiments an autoimmune or inflammatory disorder.
  • a proliferative disorder e.g., carcinoma, pre-carcinoma, or melanoma lesion, or other cancer lesion, or psoriasis
  • an autoimmune or inflammatory disorder e.g., in some embodiments, the composition is applied for treatment of rosacea or acne.
  • Autoimmune manifestations include cutaneous manifestation of lupus and dermatitis herpetiformis, or
  • the composition is applied to skin affected by shingles, providing, for example, relief from associated pain and reduction in associated rash.
  • the composition can be applied topically to affected areas of the skin, or alternatively, applied during bathing (using a soap, shampoo, or bath salt composition comprising the silica dust).
  • compositions are applied to the skin in the area of the pain (for example, to generally intact skin surrounding a painful joint).
  • the composition is applied to the affected area at least about daily for at least about 1 week, or at least about 2 weeks. In some embodiments, the composition is applied between once and ten times per day, or in some embodiments, from once to about four times per day, or from one to three times daily. In some embodiments, the regimen is continued for at least one week, or at least two weeks, or at least one month, or at least two months, or at least four months, or at least six months, or more. In some embodiments, the regimen is continued for six months or more. For subjects having a genetic disease of the skin, the regimen may be continuous.
  • Silica fibers were prepared using an electrospinning process, in which a sol- gel was spun onto a collector drum to form a non-woven mat of fibers.
  • the sol-gel was made in two parts. First, TEOS was mixed with ethanol, and then a second mixture containing HC1, water, and ethanol was titrated into the mixture. The sol-gel was then allowed to ripen for a few days under controlled conditions before spinning.
  • the first sol was made by weighing out 384 grams of TEOS 98% and 41.8 grams of anhydrous denatured ethanol, and pouring together. The first sol was allowed to let stand in a beaker, and a magnetic stirrer was used to create a homogenous solution.
  • the second sol was made by weighing 41.8 grams of anhydrous denatured ethanol, 16.4 grams of distilled water, and 0.34 grams of hydrochloric acid, which was then poured together and mixed for 8 seconds with a magnetic stirrer until a homogenous second sol was formed.
  • the second sol was then poured into the titration device, which was placed above a beaker containing the first sol.
  • the titration device then dripped about 5 drops per second until a third sol was formed via the mixing of the first sol and the second sol.
  • the first sol was continuously mixed with a magnetic stirrer while the second sol was dripped into the first sol.
  • the combined third sol was then placed into an enclosure box.
  • a low pressure vacuum was provided by a fan on medium speed to remove fumes.
  • the air temperature within the box was 72° F with 60% humidity.
  • the third sol was allowed to sit and process for about three days.
  • the mixtures were agitated daily to reduce the build-up of crystalline structures.
  • the third sol began to transition to sol-gel with evaporation of the alcohol solvent.
  • Sol-gel may be monitored to determine an approximate amount of C2H4 (ethylene) in the vapors, which may be in the range of about 10-20% relative to that of the original sol before ripening.
  • the sol-gel was loaded into electrospinning machine or was frozen to preserve for electrospinning.
  • proper gelatinization occurred when the total mass of the sol-gel was between about 70 grams and about 140 grams.
  • This example may be scaled appropriately and the ranges may vary, yet still produce desirable structures.
  • portions of the gel may be dripped into the electric field of the spinning apparatus to evaluate the spinning properties of the sol-gel.
  • FIGS. 1A-1D are scanning electron microscopy (SEM) images of fibers spun in accordance with embodiments of the invention (50, 100, 200, and 500 micron scales shown). As shown, the fibers are flexible, smooth, dense, and continuous (not significantly fractured).
  • FIG. 2 is an SEM image of fibers that were electrospun at a non-optimal time (before the sol-gel was fully ripened) (20 micron scale shown), where the fibers are clearly rigid with many fractures clearly evident.
  • FIG. 3 shows a fiber mat spun in accordance with embodiments of the invention. The flexibility and continuity of the fibers allows mats to be spun at a thickness of 1/4 inch or more. The mat has a soft, flexible texture.
  • FIGS. 4A and 4B are images comparing a silica fiber mat that was electrospun when the sol-gel was ripened in accordance with embodiments of the invention (FIG. 4A), with a fiber mat that was spun too early, before the sol-gel was optimally ripened or ripened too fast (FIG. 4B).
  • the material in FIG. 4A has a soft texture, is very flexible, and can be spun at a thickness that is easily processed into dust-like particles.
  • the material in FIG. 4B is brittle, inflexible, and thin.
  • FIGS. 5 A and 5B show SEM images of the resulting fiber dust, with 100 pm scale shown. The soft texture of the material remains evident in the dust form.
  • a silica fiber mat prepared as described above was rubbed through a 100 mesh screen.
  • the resulting silica fiber dust was incorporated into different topical compositions including: petroleum jelly, bacitracin ointment, facial cream, hand cream, and acne cream.
  • a paste was prepared with bacitracin ointment and silica fiber dust.
  • the paste was applied to the skin of a middle-age woman experiencing shingles.
  • the ointment relieved the pain associated with the shingles.
  • Petroleum jelly-silica fiber composition was also applied to affected areas with similar results.
  • FIGS. 6A and 6B An exemplary treatment of shingles is shown in FIGS. 6A and 6B.
  • FIG. 6A shows the initial shingles rash
  • FIG. 6B shows the same rash after about 1.5 days, with the topical composition being applied. Pain was also substantially reduced. Typically, it takes several weeks for a shingles rash to resolve.
  • a silica fiber composition prepared with generic facial cream was prepared as described. The composition was applied over the course of 10 days to age spots on the face of an adult male. Over 10 days the spots were substantially faded.
  • a silica fiber composition was prepared with generic hand cream. The composition was used routinely by an adult woman with scarring and dermatitis marks on her hands. Over time, the scarring and dermatitis marks subsided.
  • a silica fiber composition was prepared with acne cream, and applied to the face of a female with acne blemishes and acne scarring on her face. With routine application, the scars and blemishes subsided.
  • a silica fiber composition was applied to the torso of a middle-aged male having a first/second degree bum. With routine application, the bum was substantially healed in about 4 days (compare FIG. 7A with FIG. 7B).
  • a middle-aged male suffered 2nd and 3rd degree bums resulting from an explosion suffered 2nd and 3rd degree bums resulting from an explosion.
  • the bums covered the right hand and much of the right arm, extending from the fingers to above the elbow.
  • treatment with the silica fibers was initiated.
  • the subject was still experiencing a significant amount of pain prior to treatment.
  • a lotion composition was applied to the skin of a female subject (about 18 months of age) having harlequin Ichthyosis. It was observed that the rate at which excess skin was being produced had slowed drastically. Is was further observed that the subject’s body was better hydrated, most likely because the skin production was slower, and the extremely high caloric needs were drastically reduced.

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JP7445979B2 (ja) 2024-03-08
CN111989089A (zh) 2020-11-24

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