Use of topical formulations of cannabinoids in the treatment of epidermolysis bullosa and related connective tissue disorders
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Publication Number
US-12042479-B2
Publication Date
2024-07-23
Expiration Date
Abstract
Mutations in keratin genes or the genes that regulate keratin expression can result in epithelial cells lacking sufficient structural integrity. The resulting disruption of connective tissue gives rise to inherited disorders such epidermolysis bullosa. It has been found that various cannabinoids (including mixtures of cannabidiols and cannabinol) upregulate expression of various keratins such that loss of function in other keratin genes may be compensated for. By way of this upregulation, these cannabinoids can be used to treat epidermolysis bullosa and other connective tissue disorders arising from intermediate filament dysfunction.
Core Innovation
The disclosed invention provides topical cannabinoid-based treatment for epidermolysis bullosa (EB) by topically administering a therapeutically effective quantity of cannabinol to skin of a subject in need thereof. The administered amount is sufficient to modulate an amount or activity of one or more keratins and to stimulate wound healing when topically administered to the skin, and cannabinol is described as the only cannabinoid administered to the skin of the subject.
The disclosure links cannabinoid receptor signaling through CB1 and CB2 to keratin gene modulation in the context of intermediate filament/keratin dysfunction disorders. It describes targeting keratin expression changes, including upregulating a compensatory keratin such as K15 and/or downregulating mutated or other keratins such as K5 and K14, with attention to keratin transcription and protein synthesis.
The document also addresses cannabinoid candidates for topical pharmaceutical composition use, including classical cannabinoids, non-classical cannabinoids, endocannabinoids and derivatives, together with optional terpenoid combinations. It characterizes cannabinoid receptor selectivity and activity profiles at CB1 and CB2 and presents topical administration of cannabinoid-containing compositions intended to modulate keratins and stimulate wound healing.
Mechanistic outcomes include reduced inflammation, reduced pain/itch, reduced infection, and rescue of TGF-b-associated effects, including E-cadherin inhibition and associated pathways such as MCP-1/CCL2 production, with examples describing K5 and K14 downregulation, K15 upregulation, and wound healing enhancement in HaCaT models.
Claims Coverage
The provided independent claim coverage centers on topical treatment of epidermolysis bullosa with cannabinol as the only cannabinoid. The inventive features include a disease target, topical dosing constrained to cannabinol only, and functional requirements of keratin modulation and wound healing stimulation.
Topical cannabinol-only therapy for EB via keratin modulation and wound healing
A method for treating epidermolysis bullosa by topically administering to skin a therapeutically effective quantity of cannabinol, wherein cannabinol is the only cannabinoid administered to the skin of the subject and the quantity is sufficient to modulate an amount or activity of one or more keratins and stimulate wound healing.
Keratin expression directionality in the mitotically active basal layer
Administering a therapeutically effective topical amount sufficient to increase K15 mRNA or protein levels or decrease K5 or K14 mRNA or protein levels in the mitotically active basal layer of the skin.
Pharmaceutical composition for topical administration with pharmaceutically acceptable carrier
Providing a therapeutically effective amount of cannabinol in a pharmaceutical composition for topical administration that includes at least one pharmaceutically acceptable carrier.
Topical carrier selected from named excipients
Using a pharmaceutically acceptable carrier selected from caprylocaproyl polyoxyl-8 glycerides, poloxamer 407, lecithin, or isopropyl palmitate.
Co-administered terpenoid together in a single composition
Administering cannabinol and the terpenoid together in a single pharmaceutical composition.
The claim coverage is grounded in topical cannabinol-only treatment of epidermolysis bullosa, with a therapeutically effective amount defined by functional requirements: modulation of keratins and stimulation of wound healing. The dependent features emphasize specific keratin targets, topical formulation requirements with defined pharmaceutically acceptable carriers, and optional terpenoid inclusion in a single composition.
Stated Advantages
Stimulates wound healing when topically administered.
Modulates an amount or activity of one or more keratins.
Reduces inflammation.
Reduces pain/itch.
Reduces infection.
Rescues TGF-b-associated effects, including E-cadherin inhibition, with associated effects such as MCP-1/CCL2 production.
Provides anti-inflammatory biomarker modulation including CCL2/MCP-1 and IL-8/IL-6 in described examples.
Documented Applications
Topical treatment for epidermolysis bullosa (EB), including epidermolysis bullosa simplex (EBS) and other intermediate filament/keratin dysfunction disorders where keratin expression is to be modulated.
Treatment of epidermolysis bullosa by topically administering cannabinol to skin of a subject in need thereof.
Topical keratin modulation in keratinocyte/wound healing contexts, including wound healing metrics and keratin expression changes described in the disclosure.
Addressing TGF-b-associated effects including E-cadherin inhibition and associated pathways such as MCP-1/CCL2 production in the context of the disclosed therapeutic activity.
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