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WO2025075986A1 - Systèmes et procédés d'administration orale d'hydrogel - Google Patents

Systèmes et procédés d'administration orale d'hydrogel Download PDF

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Publication number
WO2025075986A1
WO2025075986A1 PCT/US2024/049456 US2024049456W WO2025075986A1 WO 2025075986 A1 WO2025075986 A1 WO 2025075986A1 US 2024049456 W US2024049456 W US 2024049456W WO 2025075986 A1 WO2025075986 A1 WO 2025075986A1
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WIPO (PCT)
Prior art keywords
acid
nicotine
hydrogel
cellulose
oil
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PCT/US2024/049456
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English (en)
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WO2025075986A9 (fr
Inventor
Xiang Gao
Yatao Liu
James Liang-Hiong Chia
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Scientific Horizons Consulting LLC
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Scientific Horizons Consulting LLC
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Publication of WO2025075986A1 publication Critical patent/WO2025075986A1/fr
Publication of WO2025075986A9 publication Critical patent/WO2025075986A9/fr
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B13/00—Tobacco for pipes, for cigars, e.g. cigar inserts, or for cigarettes; Chewing tobacco; Snuff
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
    • A24B15/18—Treatment of tobacco products or tobacco substitutes
    • A24B15/28—Treatment of tobacco products or tobacco substitutes by chemical substances
    • A24B15/281—Treatment of tobacco products or tobacco substitutes by chemical substances the action of the chemical substances being delayed
    • A24B15/283—Treatment of tobacco products or tobacco substitutes by chemical substances the action of the chemical substances being delayed by encapsulation of the chemical substances
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
    • A24B15/18—Treatment of tobacco products or tobacco substitutes
    • A24B15/28—Treatment of tobacco products or tobacco substitutes by chemical substances
    • A24B15/30—Treatment of tobacco products or tobacco substitutes by chemical substances by organic substances
    • A24B15/302—Treatment of tobacco products or tobacco substitutes by chemical substances by organic substances by natural substances obtained from animals or plants
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/465—Nicotine; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • 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
    • A61K31/658—Medicinal preparations containing organic active ingredients o-phenolic cannabinoids, e.g. cannabidiol, cannabigerolic acid, cannabichromene or tetrahydrocannabinol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays

Definitions

  • the polymer is selected from the group consisting of sodium alginate, pectin, pullulan, glucan, dextrin, maltodextrin, xanthan gum, xyloglucan, tragacanth gum, guar gum, acacia gum, Arabic gum, starch, agarose, gelatin, gellan, chitosan, carrageenan, chondroitin sulfate, collagen, silk fibroin, sericin, scleroglucan, cellulose, hyaluronic acid, hydroxypropyl methyl cellulose (HPMC), hydroxy ethyl cellulose (HEC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose (CMC), ethyl cellulose (EC), hydroxypropyl ethyl cellulose (HPEC), and combinations thereof.
  • the active comprises an (S)-nicotine salt, the (S)-nicotine salt further comprising a protonated (S)-nicotine cation in association with a negatively charged counterion comprising a conjugate base of an organic acid.
  • the organic acid is selected from the group consisting of formic acid, acetic acid, adipic acid, trifluoroacetic acid, aspartic acid, butanoic acid, butyric acid, 2-methylbutyric acid, 3- methylbutyric acid, benzoic acid, caprylic acid, citric acid, crotonic acid, butanoic acid, ethylenediaminetetraacetic acid (EDTA), C8-C26 saturated, monounsaturated, or polyunsaturated fatty acids, fumaric acid, gluconic acid, glutamic acid, glyceric acid, glycidic acid, glycolic acid, glyoxylic acid, hexanoic acid, heptanoic acid, lactic acid, lauric acid, levulinic acid, maleic acid, L-(-)-malic acid, malonic acid, mandelic acid, mesooxalic acid, methane sulfonic acid, oxalic acid,
  • the cyclodextrin is selected from the group consisting of P- cyclodextrin, hydroxypropyl-P-cyclodextrin, methyl-P-cyclodextrin, dimethyl-P-cyclodextrin, heptakis(2,6-di-O-)ethyl-P-cyclodextrin, 6-O-a-maltosyl-P-cyclodextrin, randomly methylated P- 15 cyclodextrin (RAMEB), sulfobutylether-P-cyclodextrin, sulfolipo-P-cyclodextrin, y- cyclodextrin, hydroxypropyl-y-cyclodextrin, octakis-(6-bromo-6-deoxy)-y-cyclodextrin, octakis- (6-amino-6- deoxy)-y-cyclodextrin, o
  • the plasticizer comprises at least one of an triglyceride vegetable oil from soybean oil, linseed oil, castor oil, or sunflower oil, citric acid, glycerin, 1,2-propylene glycol, diethylene glycol, sorbitol, and poly(ethylene glycol succinate).
  • the disintegrant is selected from the group consisting of starch, sodium starch glycolate Type A, sodium starch glycolate Type B, powdered microcrystalline cellulose (MCC), guar gum, xanthan gum, locust bean gum, chitosan hydrochloride, alginic acid, calcium alginate, sodium alginate, docusate sodium, dicalcium phosphate, tricalcium phosphate, magnesium aluminum silicate, bentonite, guargalactomannan, crosslinked sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, methylcellulose, calcium carboxymethylcellulose, croscarmellose sodium, calcium cellulose glycolate, crospovidone, and mixtures thereof.
  • MCC powdered microcrystalline cellulose
  • guar gum guar gum
  • xanthan gum locust bean gum
  • chitosan hydrochloride alginic acid, calcium alginate, sodium alginate, docusate sodium, dicalcium phosphat
  • the hydrogels provided for herein further comprise a flavoring agent.
  • the polymer is selected from the group consisting of gelatin, pullulan, acacia gum, sodium alginate, carboxymethylcellulose (CMC), hydroxypropyl methylcellulose (HPMC), and mixtures thereof.
  • a nicotine complex or product comprising (S)-nicotine primarily (greater than 50%) in the form of a free base alkaloid (e.g., non-salt) with less than 50% monoprotonated nicotine (e.g., salt) and one or more ingredients suitable for forming a complex with the (S)-ni cotine.
  • a free base alkaloid e.g., non-salt
  • monoprotonated nicotine e.g., salt
  • the acid having a polar and/or hydrophilic functional group comprises at least one hydroxyl group, at least one double bond, at least one conjugated double bond, at least one carboxyl group, or combinations thereof. In several embodiments, the acid having a polar and/or hydrophilic functional group comprises at least one hydroxyl group. In several embodiments, the acid having a polar and/or hydrophilic functional group comprises at least one double bond. In several embodiments, the acid having a polar and/or hydrophilic functional group comprises at least one conjugated double bond. In several embodiments, the acid having a polar and/or hydrophilic functional group comprises at least one carboxyl group.
  • the C8-C24 fatty acid is saturated and is selected from the group consisting of caprylic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, icosanoic acid, docosanoic acid, and tetracosanoic acid.
  • the -C24 fatty acid is polyunsaturated and is selected from the group consisting of conjugated linoleic acid, eicosadienoic acid, docosadienoic acid, pinolenic acid, a-eleostearic acid, P-eleostearic acid, catalpic acid, dihomo-y-linolenic acid, eicosatri enoic acid, eicosatetraenoic acid, adrenic acid, bosseopentaenoic acid, ozubondo acid, sardine acid, tetracosapentaenoic acid, and herring acid.
  • the fatty acid glyceride comprises one or more of sunflower oil, canola oil, palm oil, coconut oil, safflower oil, olive oil, sesame oil, peanut oil, avocado oil, or soybean oil.
  • the fatty acid glyceride comprises sunflower oil.
  • the fatty acid glyceride comprises canola oil.
  • the fatty acid glyceride comprises palm oil.
  • the fatty acid glyceride comprises coconut oil.
  • the fatty acid glyceride comprises safflower oil.
  • the fatty acid glyceride comprises olive oil.
  • the fatty acid glyceride comprises sesame oil.
  • the fatty acid glyceride comprises peanut oil.
  • the fatty acid glyceride comprises avocado oil.
  • the fatty acid glyceride comprises soybean oil.
  • the polysaccharide comprises a cyclodextrin.
  • the cyclodextrin is selected from the group consisting of P-cyclodextrin, hydroxypropyl-P-cyclodextrin, methyl-P-cyclodextrin, dimethyl-P-cyclodextrin, heptakis(2,6-di- O-)ethyl-P-cyclodextrin, 6-O-a-maltosyl-P-cyclodextrin, randomly methylated P-cyclodextrin (RAMEB), sulfobutylether-P-cyclodextrin, sulfolipo-P-cyclodextrin, y-cyclodextrin, hydroxypropyl-y-cyclodextrin, octakis-(6-bromo-6- deoxy)-y-cyclodextrin, octakis-
  • the nicotine complexes and products provided for herein further comprise an antioxidant selected from the group consisting of tocopherols (vitamin E), butylated hydroxy anisole (BHA), butylated hydroxytoluene (BHT), propyl gallate, tertiary butylhydroquinone (TBHQ), rosemary extracts, green tea extract, and combinations thereof.
  • the nicotine complexes and products provided for herein further comprise tocopherols (vitamin E).
  • the nicotine complexes provided for herein further comprise butylated hydroxy anisole (BHA).
  • the nicotine complexes and products provided for herein further comprise butylated hydroxytoluene (BHT).
  • the nicotine complexes and products provided for herein further comprise propyl gallate. In several embodiments, the nicotine complexes provided for herein further comprise tertiary butylhydroquinone (TBHQ). In several embodiments, the nicotine complexes and products provided for herein further comprise rosemary (or other herbal) extracts. In several embodiments, the nicotine complexes provided for herein further comprise green tea extract.
  • TBHQ tertiary butylhydroquinone
  • the nicotine complexes and products provided for herein further comprise rosemary (or other herbal) extracts. In several embodiments, the nicotine complexes provided for herein further comprise green tea extract.
  • the nicotine complexes and products provided for herein further comprise a substrate.
  • the substrate contributes to a physical form or a function of the nicotine product.
  • the substrate comprises a nonwoven fabric, a latex or rubber swatch, a fabric swatch, a wood splint, polymer fibers, cellulose viscose, paper, cotton, or a combination thereof.
  • substrate comprises spunbonded cotton, melt blown cotton, needle punched cotton, thermally bonded cotton, chemically bonded cotton, hydroentangled cotton, spun-laced cotton, or air-laid cotton.
  • the substrate comprises a nonwoven fabric, wherein the nonwoven fabric is saliva-permeable.
  • the nicotine complexes and products provided for herein further comprise a carrier.
  • the carrier is selected from the group consisting of water insoluble fibers, microcrystalline cellulose, bamboo fibers, lignin, wheat fibers, pea fibers, maize fibers, rice fiber, oat fibers, barley fibers, buckwheat fibers, cellulose fibers, bran fibers, powdered cellulose, and combinations thereof.
  • the carrier comprises water insoluble fibers.
  • the carrier comprises microcrystalline cellulose.
  • the carrier comprises bamboo fibers.
  • the carrier comprises lignin.
  • the carrier comprises pea fibers. In several embodiments, the carrier comprises maize fibers. In several embodiments, the carrier comprises rice fibers. In several embodiments, the carrier comprises oat fibers. In several embodiments, the carrier comprises barley fibers. In several embodiments, the carrier comprises buckwheat fibers. In several embodiments, the carrier comprises cellulose fibers. In several embodiments, the carrier bran fibers. In several embodiments, the carrier comprises powdered cellulose.
  • an oral nicotine pouch comprising a saliva-permeable nonwoven fabric, wherein the saliva-permeable nonwoven fabric defines an enclosure and a fill material within the enclosure and comprising an (S)-nicotine complex to the present disclosure and a carrier.
  • the fill material is sealed within the enclosure.
  • the carrier comprises microcrystalline cellulose.
  • the (S)-nicotine complex comprises a non-salt nicotine complex emulsion.
  • the non-salt nicotine complex emulsion comprises micelles, colloidal particles, or self-assembled structures.
  • the non-salt nicotine complex emulsion comprises micelles.
  • the non-salt nicotine complex emulsion comprises colloidal particles. In several embodiments, the non-salt nicotine complex emulsion comprises self-assembled structures. In several embodiments, the non-salt nicotine complex emulsion comprises micelles, colloidal particles, or self-assembled structures have a particle size between 10 nm to 10 pm. In several embodiments the non-salt nicotine complex emulsion comprises an unsaturated fatty acid complexed with the (S)-nicotine. In several embodiments, the unsaturated fatty acid comprises a C8-C24 fatty acid. In several embodiments, the C8-C24 fatty acid comprises conjugated linoleic acid.
  • the amount of nicotine is from about 0.1 to about 4% by weight of the pouch, including about 0.1% to about 0.5%, about 0.5% to about 1.0%, about 1.0% to about 1.5%, about 1.5% to about 2.0%, about 2.0% to about 2.5%, about 2.5% to about 3.0%, about 3.0% to about 3.5%, about 3.5% to about 4.0%, and any percentage in between those listed, including endpoints.
  • the amount of solubilizer is from about 0.1 to about 40% by weight of the pouch, including about 0.1% to about 0.5%, about 0.%% to about 1.0%, about 1.0% to about 2.0%, about 2.0% to about 3.0%, about 3.0% to about 4.0%, about 4.0% to about 5.0%, about 5.0% to about 6.0%, about 6.0% to about 7.0%, about 7.0% to about 8.0%, about 8.0% to about 9.0%, about 9.0% to about 10.0%, about 10.0% to about 15.0%, about 15.0% to about 20.0%, about 20.0% to about 25.0%, about 25.0% to about 30.0%, about 30.0% to about 35.0%, about 35.0% to about 40.0% and any percentage in between those listed, including endpoints..
  • the at least one unsaturated fatty acid comprises conjugated linoleic acid.
  • the at least one oil comprises on or both of MCT oil and sunflower oil.
  • the at least one polysaccharide comprises a cyclodextrin.
  • the cyclodextrin comprises hydroxypropyl-P-cyclodextrin.
  • the product comprises at least two of a pouch, a carrier, an antioxidant, a flavorant, or a sugar alcohol.
  • the product comprises at least three of a pouch, a carrier, an antioxidant, a flavorant, or a sugar alcohol.
  • the at least one surfactant comprises polysorbate 80.
  • a method of tailoring a subject’s nicotine experience comprising administering to the subject a nicotine complex, an oral nicotine pouch, or a nicotine product according to the present disclosure.
  • a nicotine complex for modulation of nicotine release rate and/or quantity to a subject.
  • the nicotine release rate and/or quantity is increased as compared to free base nicotine, or an oral nicotine pouch or nicotine product not comprising a nicotine complex.
  • the nicotine release rate and/or quantity is reduced as compared to free base nicotine, or an oral nicotine pouch or nicotine product not comprising a nicotine complex.
  • the polymer comprises gelatin, pullulan, acacia gum, sodium alginate, carboxymethylcellulose (CMC), hydroxypropyl methylcellulose (HPMC), or mixtures thereof.
  • the polymer comprises gelatin.
  • the polymer comprises pullulan.
  • the polymer comprises acacia gum.
  • the polymer comprises sodium alginate.
  • the polymer comprises carboxymethylcellulose (CMC).
  • the polymer comprises hydroxypropyl methylcellulose (HPMC).
  • the hydrogel comprises a (S)-nicotine salt, which comprises a protonated (S)-nicotine cation in association with a negatively charged counterion comprising a conjugate base of an organic acid.
  • the organic acid is selected from the group consisting of formic acid, acetic acid, adipic acid, trifluoroacetic acid, aspartic acid, butanoic acid, butyric acid, 2-methylbutyric acid, 3-methylbutyric acid, benzoic acid, caprylic acid, citric acid, crotonic acid, butanoic acid, ethylenediaminetetraacetic acid (EDTA), C8-C26 saturated, monounsaturated, or polyunsaturated fatty acids, fumaric acid, gluconic acid, glutamic acid, glyceric acid, glycidic acid, glycolic acid, glyoxylic acid, hexanoic acid, heptanoic acid, lactic
  • hydrogel-based oral strip comprising an active, a polymer, a plasticizer, and a disintegrant.
  • an oral nicotine pouch comprising a saliva- permeable nonwoven fabric defining an enclosure containing a hydrogel therein, said hydrogel comprising (S)-nicotine, or a salt or a complex thereof, a polymer, a plasticizer, and a disintegrant.
  • the hydrogel of the ONP further comprises a carrier.
  • an oral nicotine pouch comprising providing a saliva-permeable nonwoven fabric defining an enclosure, preparing an aqueous mixture of (S)-nicotine, a salt or a complex thereof, at least a polysaccharide or other naturally occurring hydrogel-forming polymer, at least a plasticizer, and at least a disintegrant in water, absorbing the aqueous mixture onto a carrier to form a free-flowing mixture, and disposing a portion of the free-flowing mixture in the enclosure.
  • S saliva-permeable nonwoven fabric defining an enclosure
  • preparing an aqueous mixture of (S)-nicotine, a salt or a complex thereof, at least a polysaccharide or other naturally occurring hydrogel-forming polymer, at least a plasticizer, and at least a disintegrant in water absorbing the aqueous mixture onto a carrier to form a free-flowing mixture, and disposing a portion of the free-flowing mixture in the enclosure.
  • Figure 1 schematically illustrates various embodiments of hydrogels according to the present disclosure that are configured to swell and deliver nicotine while concomitantly disintegrating in the mouth of an individual.
  • Figures 4A-4B illustrates photographs of non-limiting embodiments of dosage forms and methods of use for hydrogel -based oral strips.
  • Figure 4A shows oral application on the tongue and
  • Figure 4B shows application across the teeth and gums.
  • Figure 5 illustrates an x/y plot of nicotine delivery over time from hydrogel -based oral strips comprising (S)-nicotine lactate in comparison to nicotine delivery over time from an oral nicotine pouch (ONP) comprising (S)-nicotine lactate and only microcrystalline cellulose (MCC).
  • Figures 6A-6B illustrate x/y plots of dissolution rate of (Figure 6A) caffeine-based hydrogels from five different polymers and ( Figure 6B) melatonin-based hydrogels from three different polymers.
  • Figure 7 illustrates embodiments of oral nicotine pouches (ONPs), showing the options for traditional delivery of nicotine from a microcrystalline cellulose (MCC) carrier and modified delivery of nicotine when a novel hydrogel scaffold is used as the fill material for an ONP.
  • MCC microcrystalline cellulose
  • Figure 9 illustrates x/y plots of nicotine delivery over time from ONPs comprising (S)- nicotine lactate in a mixture of hydrogel and microcrystalline cellulose (MCC) carrier, in comparison to nicotine delivery over time from an ONP comprising (S)-nicotine lactate and only microcrystalline cellulose (MCC).
  • FIG 15 schematically depicts the components of an Oral Nicotine Pouch (ONP) dosage form where the ONP employs a cellulose-hydrogel-emulsion matrix (referred to herein at times as a CHEM).
  • ONP Oral Nicotine Pouch
  • a cellulose-hydrogel-emulsion matrix referred to herein at times as a CHEM.
  • a combination of cellulose such as microcrystalline cellulose, is formed with a hydrogel scaffold.
  • an emulsion comprising nicotine.
  • the cellulose-hydrogel- emulsion can be a water-oil -water emulsion, a water-oil emulsion, an oil-water-oil emulsion, an oil-water emulsion, a noisome, or a liposome, depending on the embodiment.
  • Figure 16 sets forth TABLE 5 listing non-limiting embodiments of hydrogel -emulsionbased oral nicotine pouch (ONP) formulations.
  • the active comprises quercetin. In several embodiments, the active comprises y-aminobutyric acid (GABA). In several embodiments, the active comprises theanine. In several embodiments, the active comprises L-tryptophan. In several embodiments, the active comprises 5-hydroxy-L- tryptophan (5-HTP). In several embodiments, the active comprises serotonin or another neurotransmitter. In several embodiments, the active comprises psilocybin. In several embodiments, the active comprises psilocin. In several embodiments, the active comprises norpsilocin. In several embodiments, the active comprises baeocystin. In several embodiments, the active comprises norbaeocystin.
  • a hydrogel composition comprises at least one of (S)-ni cotine, an (S)-nicotine salt, and an (S)-nicotine complex. Hydrogel compositions are optimized for rapid disintegration and controlled (S)-nicotine delivery in the oral cavity of an individual desirous of (S)-nicotine self-administration from a smokeless product. In various embodiments, a hydrogel composition comprises at least one active as provided for herein. Hydrogel compositions are optimized for tailored disintegration and controlled delivery of the active in the oral cavity of an individual desirous of self-administration of the active.
  • amphoteric substances include, but are not limited to, alkyl betaines, alkyl amidopropyl betaines, alkyl sulphobetaines, alkyl glycinates, alkyl carboxyglycinates, alkyl amphopropionates, alkyl amidopropyl hydroxysultaines, acyl taurates, acyl glutamates, and mixtures thereof.
  • Surfactants and polymeric substances under this broad definition are capable of forming complexes with (S)-nicotine. These complexes may be micellular in form, although no theories are proffered as to the structure of (S)-nicotine- surfactant complexes.
  • hydrogel takes on its ordinary meaning in chemistry.
  • the term may refer to a crosslinked polymer “network” (or “matrix”) having an observed rigidity and ability for absorbing a large amount of water and dimensionally swelling.
  • a hydrogel is essentially a macromolecular polymer gel comprising a network of crosslinked polymer chains. Hydrogels are sometimes said to have both solid and liquid properties. Solid because there is no observable flow, and liquid because small molecules can diffuse in and out. Swelling of hydrogels is a response to stimulus including pH, temperature and ionic strength of the solution a hydrogel is exposed to.
  • Hydrogels may be synthesized from hydrophilic monomers by either chain or step growth methods, along with a functional crosslinker to structure the network.
  • Hydrogels can be prepared from natural, synthetic or synthetic/natural hybrid polymers. Synthetic or natural polymers, homopolymer or copolymer, are used to make three dimensional networks by molecular entanglements or by chemical crosslinking. Hydrogels according to the present disclosure are preferably constructed of polysaccharides rather than synthetic polymers.
  • plasticizer takes on its ordinary meaning in organic and polymer chemistry.
  • the term may refer to a chemical compound added to a polymer to make the polymer structure softer, more flexible and flexible and less brittle, and in some instances to make a polymer more processable, such as to aid extrusion.
  • a plasticizer modifies these properties is still to date not well understood, it is believed a plasticizer somehow effects movement of polymer chains in a polymer.
  • a composition herein comprises a liquid mixture amenable to polymerization into a hydrogel.
  • the hydrogel may be formed into any suitable shape and size amenable to oral administration.
  • An “increased” or “enhanced” amount is typically a “statistically significant” amount and may include an increase in nicotine delivery that is 1.1, 1.2, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50 or more times (e.g., 500, 1000 times), including all integers and decimal points in between and above 1 (e.g., 1.5, 1.6, 1.7. 1.8), the rate of (S)-nicotine delivery by a control composition.
  • a hydrogel comprises from about 0.01 wt.% to about 10 wt.% of an (S)-nicotine salt, including about 0.02%, about 0.05%, about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, or about 9%, and any values therebetween.
  • unprotonated (S)-nicotine makes up about 15% to about 100% of the nicotine in a given complex, including about 15% to about 20%, about 20% to about 30%, about 30% to about 40%, about 40% to about 50%, about 50% to about 60%, about 60% to about 70%, about 70% to about 75%, about 75% to about 80%, about 80% to about 90%, about 90% to about 95%, about 96%, about 97%, about 98%, about 99%, or about 100%, including any values in between those ranges (including endpoints).
  • the fatty acids have at least one carboxyl group.
  • the fatty acids are unsaturated.
  • the unsaturated fatty acids comprise monounsaturated fatty acids.
  • the unsaturated fatty acids comprise polyunsaturated fatty acids.
  • the fatty acids are saturated.
  • the fatty acids include between 6 and 30 carbons in the backbone.
  • the fatty acid is a Ce fatty acid.
  • the fatty acid is a C? fatty acid.
  • the fatty acid is a Cio fatty acid.
  • the fatty acid is a C12 fatty acid.
  • Natural polymers capable of forming hydrogels include, but are not limited to, sodium alginate, pectin, pullulan, glucan (dextran), dextrin, maltodextrin, xanthan gum, xyloglucan, tragacanth gum, guar gum, acacia gum, Arabic gum, starch, agarose, gelatin, gellan, chitosan, carrageenan, chondroitin sulfate, collagen, silk fibroin, sericin, scleroglucan, cellulose, hyaluronic acid, hydroxypropyl methyl cellulose (HPMC), hydroxyethyl cellulose (ELEC), hydroxypropyl cellulose (EIPC), carboxymethyl cellulose (CMC), ethyl cellulose (EC), hydroxypropyl ethyl cellulose (HPEC), and combinations thereof.
  • forming a hydrogel from a polysaccharide can be as simple as dissolving the polysaccharide in heated deionized water and then allowing the mixture to cool into a gel.
  • any one of more of the aforementioned plasticizers may be incorporated into a hydrogel according to the present disclosure.
  • a hydrogel according to the present disclosure comprises a disintegrant.
  • a disintegrant include, but are not limited to, various starches (e.g., corn, potato, pregelatinized starch, etc.), sodium starch glycolate (Type A or B), powdered microcrystalline cellulose (MCC), guar gum, xanthan gum, locust bean gum, chitosan hydrochloride, alginic acid, calcium alginate, sodium alginate, docusate sodium, dicalcium phosphate, tricalcium phosphate, magnesium aluminum silicate, bentonite, guargalactomannan, crosslinked sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, methylcellulose, calcium carboxymethylcellulose, croscarmellose sodium, calcium cellulose glycolate, crospovidone (crosslinked polyvinylpyrrolidone), and combinations thereof.
  • Hydrogels according to the present disclosure may be tested and/or analyzed for chemical composition, mechanical properties, swelling and water uptake rate, texture and morphology, and for microbiologic contamination.
  • a hydrogel according to the present disclosure is cast into molds (sometimes referred to as “solvent casting”) or extruded into thin strips and cut to size to make oral hydrogel strips.
  • a hydrogel-based oral strip measures from about 3 cm 2 (0.5 in 2 ) to about 13 cm 2 (2.0 in 2 ) in surface area, and from about 20pm (0.8 mil) to about 3,000pm (118 mil) in thickness.
  • a preferred size for a hydrogel -based oral strip is about 3.25cm (1.28 in) x 2.2cm (0.875 in) with a thickness of about 625pm (25 mil).
  • Pouch material for use herein may be constructed from any number of various waterinsoluble nonwoven materials, called “fabrics”.
  • Fabrics Nonwoven fabrics, with their multitude of uses, are well known to those skilled in textiles. Nonwovens are described very thoroughly in “Nonwoven Fabrics: Raw Materials, Manufacture, Applications, Characteristics, Testing Processes,” editors W. Albrecht, H. Fuchs and W. Kittelmann, Wiley-VCH Verlag GmbH & Co. KgaA Weinheim, 2003.
  • Such material can be prepared by forming a web of continuous filament and/or staple fibers and optionally bonding these fibers at fiber-to-fiber contact points to provide fabrics with the desired properties.
  • the web may be simultaneously subjected to mechanical compression to obtain the desired bonding, weights and thicknesses in a process known as “thermal compression bonding.”
  • Thermal compression bonding may be accomplished by using a hot embossing roll and a heat flat calendar roll and incorporating a method in which a heat-treating machine such as a hot blast-circulating type, a hot through-air type, an infrared heater type or a vertical hot blast-blowing type is used to carry out thermal compression bonding.
  • Mechanical compression may be used to set the loft or thickness of fabrics with similar basis weights. Normally, increasing the basis weight, or the mass per square area increases thickness, and increasing bonding and compression, decreases loft.
  • a lower denier indicates a finer fiber and a higher denier indicates a thicker or heavier fiber.
  • the “mean fiber denier” is the sum of tile deniers for each fiber, divided by the number of fibers.
  • a distribution of deniers or an “average fiber denier” refers to a distribution of fiber diameters around a specific value.
  • bulk density refers to the weight of a material per unit of volume and usually is expressed in units of mass per unit of bulk volume (e.g., grams per cubic centimeter).
  • Nonwovens may be produced by fibers having a single average value of diameters or denier, or two or more average value diameter fibers may be used together.
  • two or more distributions of fiber deniers may be combined into separate fiber webs (2/2 denier and 4 denier fibers carded together for example). Then separate fiber webs may be laminated together.
  • a single nonwoven may comprise 214, 4, 6, and 15 denier fibers, meaning it was constructed with four separate denier fibers (four separate average diameters of fibers.
  • Air-laid is a well-known process by which a fibrous nonwoven layer can be formed.
  • bundles of small fibers having typical lengths of from about 3 to about 52 millimeters are separated and entrained in an air supply and deposited onto a forming screen, usually with the assistance of a vacuum.
  • the randomly deposited fibers then are bonded to one another using, for example, hot air to activate a binder component or latex adhesive.
  • the air-laying process is taught in, for example, U.S. Pat. Nos. 4,640,810 to Laursen and U.S. Pat. No. 5,885,516 to Christensen.
  • an ONP measures from about 0.12 inches to about 0.50 inches in width (or diameter) and from about 0.25 to about 0.75 inches in height.
  • a pouch may appear as a small pillow (square, or rectangular), or more like a capsule or having a cylindrical shape.
  • oral nicotine pouches ONPs herein comprise a hydrogel further comprising (S)-nicotine or a salt or a complex thereof, a polymer, a plasticizer, and a disintegrant, in accordance with the present disclosure.
  • Hydrogels that can be used in ONPs are amply described herein.
  • both a carrier and a hydrogel are used as the fill material for an ONP.
  • This combination fill material may be prepared several different ways.
  • a heated solution of polymer, an emulsion comprising (S)-nicotine or salt or complex, plasticizer and disintegrant can be cooled into a hydrogel, such as in a block.
  • the block of hydrogel may then be extruded into a granular form that can be admixed with the chosen carrier.
  • the granulated hydrogel is admixed with cellulose, such as microcrystalline cellulose (MCC) as a carrier. This dry material is then filled and sealed into nonwoven pouches.
  • MMC microcrystalline cellulose
  • a heated solution of polymer, (S)-nicotine or salt or complex, plasticizer and disintegrant such as what would be used to form a hydrogel upon cooling, is mixed with a carrier, and then that mixture is cooled into a hydrogel wherein the carrier is dispersed within the network polymer gel.
  • a portion of the resulting hydrogel, or an extruded granulate of the hydrogel may then be used as a fill material for the nonwoven pouches.
  • a heated solution of polymer, an emulsion comprising (S)-nicotine, plasticizer and disintegrant such as what would be used to form a hydrogel upon cooling is mixed with a carrier, and then that mixture is cooled into a hydrogel wherein the carrier is dispersed within the network polymer gel.
  • a portion of the resulting hydrogel, or an extruded granulate of the hydrogel may then be used as a fill material for the nonwoven pouches.
  • Carriers for use in forming hydrogel -carrier combination fill material include, but are not limited to, agar, agarose, albumin, alginate, casein, chitin, chondroitin, dextrin, fibroin, fucoidans, galactans, gellan, guar, scleroglucan, pullulan, xyloglucan, pectin, xanthan, psyllium, silica gel, fumed silica, magnesium aluminum silicates, clay, bentonite, hectorite, mesoporous silica, cellulose, cellulose acetate, hyaluronan, various elastin-like polypeptides, P-cyclodextrin, collagen, gelatin, chitosan, carrageenan, polylactic acid, polyglycolic acid, poly actic-glycolic acid) (PLGA), poly(2-hydroxyethyl methacrylate), poly(2-hydroxypropyl
  • Figure 4 illustrates examples of hydrogel-based oral strips, obtainable by casting mixtures per above into thin sheets and then cutting into strips. These strips may be used on the tongue or across the teeth and/or gums for oral delivery of (S)-nicotine as shown in the example photographs.
  • hydrogel in combination with microcrystalline cellulose (MCC) carrier modulates (S)-nicotine delivery into PBS buffer over the control ONP comprising (S)-nicotine lactate and only microcrystalline cellulose (MCC) as the fill material.
  • MCC microcrystalline cellulose
  • the choice between a variety of hydrogel polymers demonstrates the flexibility to either decrease nicotine release (gelatin, HPMC, or pullulan) or increase nicotine release (acacia gum, CMC, tapioca maltodextrin, or sodium alginate) relative to an ONP using only MCC as the carrier.
  • FIG. 12 sets forth TABLE 2 listing of non-limiting examples of hydrogel-based caffeine oral strip formulations. As discussed, a variety of polysaccharides or other naturally occurring hydrogel-forming polymers may be employed. These examples also demonstrate use of a flavoring agent such as menthol, and a sweetener such as stevia.
  • FIG. 13 sets forth TABLE 3 listing of non-limiting examples of hydrogel -based melatonin oral strip formulations. As discussed, a variety of polysaccharides or other naturally occurring hydrogel-forming polymers may be employed. These examples also demonstrate use of a sweetener such as stevia in the compositions.
  • FIG. 14 sets forth TABLE 4 listing of non-limiting examples of hydrogel -based oral nicotine pouch (ONP) formulations.
  • OTP oral nicotine pouch
  • a variety of polysaccharides or other naturally occurring hydrogel-forming polymers may be employed. These examples also demonstrate use of a flavoring agent such as menthol, and a sweetener such as stevia.
  • FIG. 15 schematically summarizes a non-limiting embodiment an Oral Nicotine Pouch (ONP) dosage form where the ONP employs a cellulose-hydrogel-emulsion matrix (referred to herein at times as a CHEM).
  • ONP employs a cellulose-hydrogel-emulsion matrix
  • CHEM cellulose-hydrogel-emulsion matrix
  • a combination of cellulose, such as microcrystalline cellulose is formed with a hydrogel scaffold.
  • Incorporated into the hydrogel scaffold is an emulsion comprising nicotine.
  • Figure 17 shows various non-limiting chemical structures of ingredients of hydrogels provided for herein.
  • Figure 18 depicts experimental data comparing the nicotine release rate from various non-limiting examples of hydrogel. Release rates measured herein are performed using a system comprising a piston pump that draws media from a media reservoir and pumps media along a closed-loop fluid flow pathway 1820 through a heat exchanger and then to a flow through cell, with the heat exchanger functioning to maintain the temperature of the media passing through the cell.
  • the dosage form being tested here oral pouches comprising hydrogel -nicotine emulsion formulations as provided for herein, is positioned within the flow cell and the media is passed through the flow cell and returns to the media reservoir in a closed-loop fashion. Samples can be withdrawn from the media reservoir at predetermined time intervals either manually or by an automated syringe system. The samples can be analyzed for concentration of API release from the dosage form.
  • the CMC -based CHEM released nicotine at a slower rate than both the gelatin-based CHEM and the water-based control.
  • This tunable nature has practical implications in some embodiments, in that an enhanced release rate suggests that, over a given time interval, a greater percentage of the active within the pouch is released. This coordinately means that over a usage time frame, there is a decrease in waste (e.g., active that remains in the pouch after use).
  • waste e.g., active that remains in the pouch after use.
  • actives integrated into hydrogel emulsions as provided for herein allow for more efficient overall release and less active agent being wasted. Also, in some cases, that means that a smaller amount of active agent can be included in such a product, reducing production costs.
  • FIGs 19A-19B show data for the release rate of nicotine (19A) and a non-limiting example of a flavorant, herein vanillin (VL) (19B).
  • VL vanillin
  • FIG 19A four different vanillin containing CHEM-ONPs were tested, acacia gum-based (AG), gelatin-based (Gel), pullulan-based (Pol), and hydroxypropyl methylcellulose-based (HPMC). Each of these four formulations exhibited similar nicotine release rates over the course of the experiment.
  • Figures 20A-20F show data related to release rate of nicotine and vanillin from five different CA containing CHEM-ONPs were tested, acacia gum-based (AG) (20A), carboxymethyl cellulose-based (CMC) (20B), gelatin-based (Gel) (20C), water-based control (H2O) (20D), hydroxypropyl methylcellulose-based (HPMC) (20E), and pullulan-based (Pol) (20F).
  • AG-based formulation allowed parallel release of nicotine and vanillin, both greater than the rates from water-based control (20D).
  • Figures 20B, 20C, 20E and 20F each show that the respective formulations tested offer different nicotine and vanillin release rate profdes than control. Again, these data reinforce that, in several embodiments, modulation of both active agent and another ingredient, like a flavorant, can be modulated to achieve a desired overall profde.
  • hydrogel of embodiment 1, comprising an (S)-nicotine salt, further comprising protonated (S)-nicotine cation in association with a negatively charged counterion comprising a conjugate base of an organic acid selected from the group consisting of formic acid, acetic acid, adipic acid, trifluoroacetic acid, aspartic acid, butanoic acid, butyric acid, 2-methylbutyric acid, 3- methylbutyric acid, benzoic acid, caprylic acid, citric acid, crotonic acid, butanoic acid, ethylenediaminetetraacetic acid (EDTA), C8-C26 saturated, monounsaturated, or polyunsaturated fatty acids, fumaric acid, gluconic acid, glutamic acid, glyceric acid, glycidic acid, glycolic acid, glyoxylic acid, hexanoic acid, heptanoic acid, lactic acid, lauric acid, levulinic
  • an organic acid
  • cyclodextrin is selected from the group consisting of
  • 3-cyclodextrin hydroxypropy
  • the plasticizer comprises at least one of an epoxidized triglyceride vegetable oil from soybean oil, linseed oil, castor oil, or sunflower oil, citric acid, glycerin, 1,2-propylene glycol, di ethylene glycol, sorbitol, and poly(ethylene glycol succinate).
  • each strip configured as a thin rectangular shape measuring from about 3 cm2 (0.5 in2) to about 13 cm2 (2.0 in2) in surface area, and from about 20pm (0.8 mil) to about 3,000pm (118 mil) in thickness.
  • An oral nicotine pouch comprising a saliva-permeable nonwoven fabric defining an enclosure containing a hydrogel therein, said hydrogel comprising (S)-nicotine, or a salt or a complex thereof, a polymer, a plasticizer, and a disintegrant.
  • aqueous solution or suspension comprising the (S)-nicotine, salt, or complex thereof, a polysaccharide or other naturally occurring hydrogel -forming polymer, a plasticizer, and a disintegrant; adsorbing the aqueous solution or suspension onto the carrier to form the fill material; and disposing the fill material inside the saliva-permeable nonwoven fabric pouch; or
  • the carrier is selected from the group consisting of agar, agarose, albumin, alginate, casein, chitin, chondroitin, dextrin, fibroin, fucoidans, galactans, gellan, guar, scleroglucan, pullulan, xyloglucan, pectin, xanthan, psyllium, silica gel, fumed silica, magnesium aluminum silicates, clay, bentonite, hectorite, mesoporous silica, cellulose, cellulose acetate, hyaluronan, various elastin-like polypeptides, P-cyclodextrin, collagen, gelatin, chitosan, carrageenan, polylactic acid, polyglycolic acid, poly(lactic-glycolic acid) (PLGA), poly(2-hydroxyethyl methacrylate), poly(2-hydroxypropyl methacrylate), poly

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Abstract

Dans divers modes de réalisation, l'invention concerne de nouveaux hydrogels capables de libérer un actif tel que la (S)-nicotine lors de l'absorption d'eau et du gonflement. Dans certains exemples, les hydrogels comprennent de la (S)-nicotine, ou un sel ou un complexe de celle-ci, au moins un polymère, au moins un plastifiant et au moins un désintégrant. Dans certains modes de réalisation, un hydrogel est utilisé en tant que support de distribution unique pour la libération de nicotine. Dans d'autres modes de réalisation, l'hydrogel est composé avec d'autres supports pour former des matériaux de remplissage avec une combinaison d'hydrogel-support utilisables pour la libération de nicotine. Les hydrogels de la présente invention comprennent de préférence un réseau polysaccharidique ou des polymères formant un hydrogel d'origine naturelle plastifiés pour assurer une flexibilité et comprenant un désintégrant afin d'accélérer la décomposition de l'hydrogel lorsqu'il est utilisé dans la cavité buccale d'un individu pour l'administration de nicotine.
PCT/US2024/049456 2023-10-03 2024-10-01 Systèmes et procédés d'administration orale d'hydrogel Pending WO2025075986A1 (fr)

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Publication number Priority date Publication date Assignee Title
WO2022214444A1 (fr) * 2021-04-06 2022-10-13 Swedish Match North Europe Ab Produit oral aromatisé à base de nicotine en sachet comprenant un acide
US20220346436A1 (en) * 2021-04-22 2022-11-03 Nicoventures Trading Limited Orally dissolving films

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022214444A1 (fr) * 2021-04-06 2022-10-13 Swedish Match North Europe Ab Produit oral aromatisé à base de nicotine en sachet comprenant un acide
US20220346436A1 (en) * 2021-04-22 2022-11-03 Nicoventures Trading Limited Orally dissolving films

Non-Patent Citations (1)

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Title
HOLLERER ET AL.: "Human metabolism and kinetics of tri-(2-ethylhexyl) trimellitate (TEHTM) after oral administration", ARCH TOXICOL., 9 September 2018 (2018-09-09), pages 1 - 2, DOI: 10.1007/s00204-018-2264-2 *

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