Compositions and methods of use for treating aberrant inflammation in peri-ocular secretory glands or at the ocular surface

A composition and ocular surface technology, applied in drug combination, drug delivery, pharmaceutical formulation, etc., can solve problems such as delayed healing, low corneal permeability, and poor

Pending Publication Date: 2020-07-03
AXEROVISION INC
View PDF13 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, topical eye drops have several disadvantages: 1) they are difficult for the patient to physically administer; 2) there are some physical and physiological barriers that protect the eye and significantly reduce the amount of drug delivered (e.g., low corneal permeability, blinking reflex and tear turnover); 3) epithelial tight junctions prevent diffusion of larger molecules
However, only short-term use of topical ophthalmic corticosteroids given as eye drops is generally recommended because long-term use may lead to adverse ocular events, including increased intraocular pressure (IOP), cataracts, and ocular infections (Becker, 1964 ; Bowling and Russell, 2011; Dinning, 1976)
[0010] Although steroid ointments/creams are widely used t

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Compositions and methods of use for treating aberrant inflammation in peri-ocular secretory glands or at the ocular surface
  • Compositions and methods of use for treating aberrant inflammation in peri-ocular secretory glands or at the ocular surface
  • Compositions and methods of use for treating aberrant inflammation in peri-ocular secretory glands or at the ocular surface

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0146] Example 1 : Effects of treatment with compounds of formula I on intraocular pressure (IOP) and tear formation

[0147] Compounds of formula I are fluorinated glucocorticoids with anti-inflammatory activity (see US Pat. No. 7,288,536). Compounds of formula I exhibit near full agonism in various in vitro assays of human glucocorticoid receptor-mediated counter-inhibitory activity, and in many assays of glucocorticoid receptor-mediated transactivation Partial response. In vivo, compounds of formula I show potent anti-inflammatory activity following intratracheal administration in mouse and rat models of pulmonary inflammation and local delayed-type hypersensitivity ear inflammation in mice , tyrosine aminotransferase-induced and chronic house dust mite models exhibit similar activity to fluticasone propionate (FP). Interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNFα) stimulate the pro-inflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) in multip...

Embodiment 2

[0153] Example 2: Determination of properties of periocular cream formulations

[0154] In this study, the following active pharmaceutical ingredients (APIs) were mixed with a cream vehicle to prepare a cream containing 2 wt% API and allowed to stand at room temperature for 24 hours prior to testing. Cyclosporine A (Sample A), Loteprednol Ecarb (Sample B), Dexamethasone (Sample C), Ketorolac Trimethylamine (Sample D), Gatifloxacin, USP (Sample E), Gentamicin sulfate (sample F), prednisolone (sample G), flurbiprofen (sample H), azithromycin dihydrate (sample J), ​​triamcinolone acetonide (sample K), and doxycycline hydrochloride (Sample L). The carrier cream contains 48% by weight of white petrolatum, 8% by weight of mineral oil, 8% by weight of propylene glycol, 6.6% by weight of ST-Cyclomethicone-5NF, 3.3% by weight of Emulsifier-10, 2% by weight of ST-Elastomer-10, 0.08% by weight methylparaben, 0.06% by weight disodium hydrogen phosphate anhydrous, 0.0546% by weight anhyd...

Embodiment 3

[0163] Example 3: Skin Penetration of Eye Cream

[0164] An in vitro skin penetration model of human cadaver skin mounted in a Franz-type diffusion cell (FDC) was chosen to determine the skin permeability of a 2% cream of the compound of formula I applied to the epidermal surface. Transdermal flux into the receiving fluid was measured within 46 hours after application of the formulation. At the end of the 46 hour incubation period, the skin was tape stripped and thermally separated based on established methods, and the concentration of the compound of formula I was measured in the remaining epidermis and dermis. The applied formulation contained: 2% by weight of compound of formula I, 46% by weight of white petrolatum, 8% by weight of mineral oil, 8% by weight of propylene glycol, 6.6% by weight of ST-cyclomethicone-5NF, 3.3% by weight of Emulsifier-10, 2 wt% ST-Elastomer-10, 0.08 wt% methylparaben, 0.06 wt% disodium hydrogen phosphate anhydrous, 0.05 wt% anhydrous citric aci...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
Solubilityaaaaaaaaaa
Login to view more

Abstract

Provided herein are pharmaceutical compositions comprising a therapeutically effective amount of a lipophilic compound and a pharmaceutically acceptable carrier adapted for peri-ocular transdermal delivery of the lipophilic compound to one or more periorbital glands and/or the ocular surface tissues of a subject. Further provided herein are methods of using such pharmaceutical compositions for providing relief of one or more signs or symptoms of an ocular disease, methods of using one or more Meibomian glands (and meibum therein) as a drug delivery system for a lipophilic compound (e.g., a steroid) to the ocular surface, and kits related thereto.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS [0002] This application claims priority to U.S. Provisional Application 62 / 589,493, filed November 21, 2017, entitled "Compositions and Methods for the Treatment of Abnormal Inflammation in the Periocular Secretory Glands or on the Ocular Surface," the entire contents of which are via Incorporated herein by reference. [0003] Field of Invention [0004] The present invention relates to pharmaceutical compositions suitable for periocular transdermal delivery of one or more lipophilic compounds; methods of their use; and kits comprising such pharmaceutical compositions. Background technique [0005] Topical drops have become the delivery method of choice for eye care practitioners, especially for conditions such as dry eye, uveitis, bacterial conjunctivitis, and glaucoma, as the ocular surface is considered the primary target tissue for drug delivery. When the drops hit the eye, the three parts of the anterior segment (ie, the ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K9/00A61K47/06
CPCA61K9/0014A61K9/0048A61K47/06A61K9/06A61K31/436A61K31/568A61K31/196A61K31/202A61K31/232A61K31/454A61K31/4725A61K31/5575A61K31/56A61K31/573A61K31/7048A61K31/7052A61K2300/00A61K47/186A61K47/10A61K45/06A61P27/02A61K47/02A61K47/12A61K47/34
Inventor C·F·波斯沃斯A·H·克劳斯
Owner AXEROVISION INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products