Sap and peptidomimetics for treatment of eye disease

An effective treatment and eye technology, applied in the fields of peptides, peptide sources, sensory diseases, etc., can solve the problems of not long-term use of corticosteroids, contraindications to patients, etc.

Pending Publication Date: 2021-01-01
ARCH BIOSURGERY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, corticosteroids are not ideal for long-term use due to possible side effects, and this regimen is often contraindicated in patients

Method used

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  • Sap and peptidomimetics for treatment of eye disease
  • Sap and peptidomimetics for treatment of eye disease
  • Sap and peptidomimetics for treatment of eye disease

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0342] Example 1: SAP exhibits therapeutic effects in the eye

[0343] The anti-inflammatory effect of SAP was examined using a lipopolysaccharide ocular inflammation model, and the measurement of microglial activation was evaluated as an indicator of inflammation. Morphological changes in macrophages, such as microglia, can be used as markers of the presence and extent of inflammation. Methods for identifying and scoring microglial morphological changes in response to inflammatory stimuli are described in the art (see, e.g., Jonas et al., PLOS ONE 7(2):e30763 (2012) ).

[0344] Methods and Materials

[0345] animal

[0346] Adult white Sprague-Dawley rats weighing between 200 and 240 grams were housed on a 12 hr light / 12 hr dark cycle with free access to food and water. Animals were randomly divided into study or control groups.

[0347] intravitreal injection

[0348] Animals were anesthetized by intraperitoneal injection of 2% xylazine (5 mg / kg body weight) and 10% ...

example 2

[0368] Example 2: (RADA) 2 and EARA-based SAP exhibit therapeutic effects on the eye

[0369] Methods and Materials

[0370] animal

[0371] Adult White Sprague-Dawley rats weighing between 200 and 240 grams were housed on a 12 hr light / 12 hr dark cycle with free access to food and water. Animals were randomly divided into study or control groups.

[0372] processing and analysis

[0373] Intravitreal injections, immunohistochemical staining and assessment of intraocular inflammation were generally performed as described in Example 1.

[0374] Administered by direct intravitreal injection alone or with 0.1%, 1.0% and 10.0% (RADA) 2 (SEQ ID NO: 88) solution combined with 1 μl of sterile lipopolysaccharide (LPS; from Salmonella typhimurium, catalog number L-7261; Sigma-Aldrich, St. Louis, MO). Animals were sacrificed 24 hours after treatment. Repeat the experiment at least 5 times.

[0375] In some experiments, as above for (RADA) 2 (SEQ ID NO:88), the evaluation cont...

example 3

[0382] Example 3: Delivery of SAP to the retina by application of eye drops

[0383] The fate of SAP when applied to the eye was investigated. Specifically, the ability of SAP to reach the retina by applying the SAP eye drop solution to the cornea was evaluated using the SAP-Cy5 conjugate.

[0384] method

[0385] animal

[0386] Adult White Sprague-Dawley rats weighing between 200 and 240 grams were housed on a 12 hr light / 12 hr dark cycle with free access to food and water. Animals were randomly divided into experimental or control groups.

[0387] Conjugation of Cy5.5 to RADA

[0388] Cy5.5 and RADA (SEQ ID NO:57), Cy5.5 and RADARADA ((RADA) 2 ; SEQ ID NO:88) and Cy5.5 and H 2 N(RADA) 4 CONH 2 The conjugate of (SEQ ID NO:433) was prepared according to a modified protocol of Chen X. et al., Cancer Res., 64(21):8009-8014 (2004).

[0389] In one experiment, the RADA-4-Cy5.5 conjugate was prepared as follows: 0.5 mg of H 2 N(RADA) 4 CONH 2 Dissolve in 50 μL of DMS...

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Abstract

Self-assembling peptides or self-assembling peptidomimetics ("SAP") can treat or alleviate disease, disorder, injury or one or more symptoms of diseases or disorders of the eye, including ocular inflammation, dry eye, corneal erosion, retinal detachment, and other problems where the barrier formed by the SAP provides protection and aids healing. SAP topical or injectable compositions of SAP for local administration to the eye include SAP in an amount and concentration effective to provide an SAP structure on or within the eye or a compartment or structure thereof. The SAP can be assembled prior to or after the composition is administration. SAP can also be used as coatings for contact lens, intraocular lens, and wound healing devices, to enhance healing and decrease inflammation.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of and priority to U.S.S.N. 62 / 647,184, filed March 23, 2018, which is hereby incorporated by reference in its entirety. [0003] References to Sequence Listings [0004] Sequence listing created on March 14, 2019 and 114,130 bytes in size as a text file named "CNS_109_ST25.txt" filed on March 15, 2019 Approved under 37 C.F.R. §1.52(e)(5) References are hereby incorporated. technical field [0005] The present invention is in the field of therapeutic agents, in particular compositions of SAP useful for treating, preventing or alleviating symptoms of diseases, disorders, injuries and related symptoms affecting the eye. Background technique [0006] The outer covering of the eyeball consists of a relatively hard white layer called the sclera (or white of the eye). In the area near the front of the eye protected by the eyelids, the sclera is covered by a clear membrane (conjunctiv...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/10A61K38/08A61K9/00G02B1/04A61P27/02A61P27/06
CPCG02B1/043A61K9/0019A61K9/0048A61K38/08A61K38/10A61P27/02A61P27/06C07K4/00A61K45/06A61K9/10A61K9/06
Inventor T·W·诺奇R·埃利斯-比恩克
Owner ARCH BIOSURGERY
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