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An eye drop solution for enhanced hyaluronic acid retention and delivery

a technology of hyaluronic acid and eye drops, which is applied in the direction of drug compositions, peptide/protein ingredients, sense disorders, etc., can solve the problems of low ocular residence time (10 min), affecting the performance of everyday activities, and high concentration of ha-based eye drops, etc., to achieve the effect of enhancing the availability of ha

Inactive Publication Date: 2019-01-03
THE JOHN HOPKINS UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent is about developing biomaterials that can mimic the smooth, hydrated, and lubricated surface of the eye. These materials can enhance the availability of a thin film of moisture that helps to keep the eye healthy and comfortable.

Problems solved by technology

Symptoms include discomfort, dryness or lack of hydration, visual disturbances and pain in the eye, which can hinder the performance of everyday activities (Abetz, Rajagopalan et al.
Although dry eye is a multifactorial disease, it occurs mostly due to any alterations in the tear film composition and stability with potential damage to the ocular surface.
2013); however, these strategies are temporary, involving the application of a saline or an emulsion-based eye drop to reduce discomfort and increase water retention at the ocular surface (Young, Veys et al.
These artificial tears must be reapplied frequently owing to their short residence time in the eye.
HA eye drop solutions effectively wet and lubricate the contact lens and ocular surfaces, however similar to saline, poly(vinyl alcohol) / PVA, methyl cellulose (MC) and hydroxypropyl methylcellulose (HPMC)-based eye drops, they suffer from low ocular residence time (<10 min) due to limited adherence to ocular surface (Snibson, Greaves et al.
Conversely, highly concentrated HA-based eye drops are too viscous and interfere with vision and blinking (Marner, Mooller et al.

Method used

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  • An eye drop solution for enhanced hyaluronic acid retention and delivery
  • An eye drop solution for enhanced hyaluronic acid retention and delivery
  • An eye drop solution for enhanced hyaluronic acid retention and delivery

Examples

Experimental program
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Effect test

example 1

[0141]Peptide screening: selecting peptide that binds to the ocular tissues.

[0142]We screened multiple peptides that are supposed to bind different sites of the ocular tissues and cells (data not shown). Out of the 6 screened peptides, a sialic acid binding peptide GGSPYGRC (SEQ ID NO: 15) hereafter respectively referred to as SABpep, and a collagen binding peptide SYIRIADTNIT (SEQ ID NO: 12) hereafter respectively referred to as ColBpep were chosen for further experiments (FIG. 2A). The chosen SABpep and ColBpep exhibited little to no cytotoxicity to epithelial cells as well (data not shown)

example 2

[0143]SABpep and ColBpep binding on conjunctiva tissue.

[0144]Rabbit conjunctival sections bound SABpep specifically on the epithelial lining of the conjunctiva (FIG. 2B), indicating the strong presence of sialic acid on mucin-1 as compared to mucin-1 antibody staining. A higher magnification confirmed that SABpep staining was localized to only on cell membranes (FIG. 2C). Conversely, as expected, ColBpep staining was localized on conjunctiva tissue more indiscriminately, which is similar to type I collagen antibody staining (FIG. 2B). The binding specificity of SABpep was further proven by sialidase digestion and pre-incubation with sialic acid. SABpep could not bind to conjunctival epithelium if the section was digested by sialiadase before staining. However, SABpep still stained the epithelium even after preincubation with sialic acid solution (data not shown).

example 3

[0145]Mucin and HA binding studies by Quartz Crystal Microbalance with Dissipation (QCM-D) monitoring.

[0146]Surface binding of polymer-peptide conjugates to mucin and HA was directly measured using QCM-D. First, sialic acid bearing mucin was adsorbed on gold substrates to mimic the interface at the corneal epithelium (FIG. 3A), as native mucin from bovine submaxillary glands is abundant with O-linked oligosaccharide chains, and can be used as a source of sialic acids. A visco-elastic layer of highly hydrated mucin was formed as shown by a frequency change of Δf=−32 Hz and dissipation change of ΔD=7. Then SABpep-PEG-HABpep was applied to the mucin layer and specific binding was indicated with a frequency change of Δf=−5 Hz. In turn, SABpep-PEG-HABpep was immobilized onto HA substrates with a Δf=−3 Hz (FIG. 3B). The Voigt mass quantified the consistent formation of visco-elastic substrates Mucin and HA (FIG. 3C). In turn, HApep binding showed a frequency but not a dissipation change. ...

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Abstract

The present invention provides biomaterial compositions that can immobilize HA to the ocular surfaces through an HABpep and transmembrane mucins and collagen of ocular tissues can act as anchoring sites. These biomaterial compositions provide prolonged HA binding and retention in both ex vivo and in vivo animal models. HA eye drop solutions with these the inventive biomaterials can prolong the biological and physical benefits to the ocular surface and potentially be more effective in treating eye disorders including dry eye than standard HA-eye drop presently available. Methods of making and use of the compositions are also provided.

Description

REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of International Patent Application No. 62 / 207,419, filed Aug. 20, 2015, which is hereby incorporated by reference for all purposes as if fully set forth herein.INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ELECTRONICALLY[0002]The instant application contains a Sequence Listing which has been submitted in ASCII format via EFS-Web and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Aug. 12, 2016, is named P13662-02_ST25.txt and is 4,807 bytes in size.BACKGROUND OF THE INVENTION[0003]Dry eye is a prevalent ophthalmic condition especially to elderly population, affecting over 15% of the US population (Ding and Sullivan 2012). Symptoms include discomfort, dryness or lack of hydration, visual disturbances and pain in the eye, which can hinder the performance of everyday activities (Abetz, Rajagopalan et al. 2011; Pouyeh, Viteri et al. 2012; Pili, Kastelan et al. 2014). Although ...

Claims

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Application Information

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IPC IPC(8): A61K47/60A61K38/08A61K31/728A61P27/04
CPCA61K47/60A61K38/08A61K31/728A61P27/04H01L24/75H01L2224/75745H01L2224/75821H01L24/00H01L21/67092H01L21/67132
Inventor SINGH, ANIRUDHAELISSEEFF, JENNIFER H.LEE, DAVIDLU, NICOLE
Owner THE JOHN HOPKINS UNIV SCHOOL OF MEDICINE
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