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Use of topical formulations of cannabinoids in the treatment of epidermolysis bullosa and related connective tissue disorders

A Cannabinoid, Topically Applied Technology, Applied to Cannabidiol and Cannabidiol: Cannabis, Topically Applied Cannabinoids, Improved Methods and Compositions for Topical Treatment of Such Diseases and Conditions, Epidermolysis Bullosa Simplex Field , can solve the problems of increasing the risk of serious infection in patients and limited application

Inactive Publication Date: 2019-04-26
因美制药公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Other treatments, such as the administration of sulforaphane or the use of bone marrow transplantation, have been proposed, but their use is limited; specifically, bone marrow transplantation requires not only a genetically compatible donor, but also the administration of strong immunosuppressive agents , which greatly increases the risk of serious infection in patients with massive blisters and skin erosions

Method used

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  • Use of topical formulations of cannabinoids in the treatment of epidermolysis bullosa and related connective tissue disorders
  • Use of topical formulations of cannabinoids in the treatment of epidermolysis bullosa and related connective tissue disorders
  • Use of topical formulations of cannabinoids in the treatment of epidermolysis bullosa and related connective tissue disorders

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0292] Example 1: Cannabinoids regulate keratin expression in HaCat cells

[0293] The materials to be tested are the phytocannabinoid cannabidiol (CBD), cannabidiol acid (CBDA), cannabidiol (CBN), cannabidiol: cannabidiol (1: 0.1 μM), cannabidiol: cannabidiol (0.1 : 1μm) and cannabidiol: cannabidiol (1:1μM).

[0294] Cell culture was carried out as follows: in Duchenne supplemented with 10(V / V)% fetal bovine serum (FBS; Life Technologies Hungary Ltd.) and an antibiotic mixture (1:100 penicillin and streptomycin; PAA Laboratories GmbH, Pasching, Austria) Modified Eagle Medium (DMEM; Life Technologies Hungary Ltd.) and HaCaT (human immortalized keratinocyte cell line) was cultured in Antimicotic (1:200; Life Technologies Hungary Ltd.).

[0295] Containing 5% CO 2 The cells were cultured at 37°C in a humidified atmosphere, the medium was changed every other day, and the cells were subcultured at 70-80% confluence in all cases. For medication, the medium is changed daily.

[0296] Qu...

Embodiment 2

[0330] Example 2: Topical cannabinoid formulation and skin penetration

[0331] The skin penetration of the formulation described herein is measured according to the following procedure: The formulation is Labrasol, Plo-gel (Poloxomer 407, lecithin, isopropyl palmitate). The formulation is applied to the center part of the circle and wiped onto the skin with a scalpel. Mount the sample on the top of the Franz diffusion cell with the outer layer of the skin facing up. The receptor medium of the Franz cell is filled with phosphate buffer. Install the diffusion cell cover and clamp it. Place the construct in an incubator / shaker at 32°C for 18 hours ( Figure 14 ). Figure 15 show Figure 14 The results of the penetration experiment (◆, 6 hours; ■, 9 hours; ▲, 12 hours).

[0332] Figure 16 Shows the use of Levenberg-Marquardt fitting and based on Figure 15 The result is a mathematical model of the cannabinoid skin spread. Figure 17 The area under the curve for allantoin (left pa...

Embodiment 3

[0333] Example 3: Cannabinoids and wound healing

[0334] Figure 19 It is an illustration of a model developed based on the experimental results described in this article. This model illustrates that endocannabinoids and cannabinoid receptors are involved in multiple regulatory systems in the skin.

[0335] Figure 20 It is a graph showing the effect of different mixtures of INM-505 (cannabidiol) and INM-517 (cannabidiol) on type II (K5, K6, and K14) and type I (K15, K16, K17) keratin expression. INM-505 and INM-517 alone or in combination (INM-505:INM-517) generally increase K5, 14, 15, 16, and 17 protein expression in differentiated human keratinocytes (concentration-dependent effect).

[0336] Figure 21 Shows that cannabinoids up-regulate the activity of extra domain A (EDA)-fibronectin in wound healing (left panel). Cannabinoids rescued the inhibitory effect of TGF-β-induced E-cadherin (right panel).

[0337] Transforming growth factor (TGFβ1)β is the main regulator of normal...

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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 thatloss 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.

Description

[0001] cross reference [0002] This application claims the benefits of U.S. Provisional Application No. 62 / 331,633 filed on May 4, 2016, the content of which is incorporated herein by reference in its entirety and used for all purposes. Background of the invention [0003] This application relates to methods and compositions for the treatment of diseases and conditions associated with dysfunction of the intermediate filaments, in particular the topical application of cannabinoids. Intermediate filaments are a large group of structurally elastic polymer proteins that give cells mechanical strength. Intermediate filaments are composed of proteins expressed in many different types of cells. Keratin is the main structural component of intermediate filaments in epithelial cells (including epithelial cells of the skin). Human skin is composed of two main layers: the outermost layer is called the epidermis, and the lower layer is called the dermis. In individuals with healthy skin, th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/352A61K31/05A61K31/122A61K31/343A61K31/397A61K31/404A61K31/415A61K31/4162A61K31/4172A61K31/473A61K31/5383A61P17/00
CPCA61K31/05A61K9/0014A61K45/06A61K31/045A61K31/352A61P17/00A61K2300/00
Inventor S.侯赛因
Owner 因美制药公司
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