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Methods of protecting vascular integrity induced by targeted radiation therapy

A radiotherapy and integrity technology that can be used in X-ray/γ-ray/particle irradiation therapy, pharmaceutical formulations, medical preparations with non-active ingredients, etc., and can solve problems such as unmet requirements

Pending Publication Date: 2020-07-17
JANSSEN PHARMA NV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The effect of TPO or TPO mimics on vascular changes induced by targeted radiotherapy has not been reported
[0008] There is an important and unmet need for methods and compositions that provide protection of normal tissue following radiation therapy

Method used

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  • Methods of protecting vascular integrity induced by targeted radiation therapy
  • Methods of protecting vascular integrity induced by targeted radiation therapy
  • Methods of protecting vascular integrity induced by targeted radiation therapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0083] The present invention also provides the following non-limiting embodiments.

[0084] Embodiment 1 is in a method of protecting vascular integrity in a subject exposed to targeted radiation therapy, the method comprising administering to the subject an effective amount of a thrombopoietin (TPO) mimetic.

[0085]Embodiment 1(a) is the method of embodiment 1, wherein the TPO mimetic comprises a peptide having the amino acid sequence of SEQ ID NO:1.

[0086] Embodiment 1(b) is the method of embodiment 1(a), wherein the peptide has the amino acid sequence of SEQ ID NO:2.

[0087] Embodiment 1(c) is the method of embodiment 1(a) or 1(b), wherein the TPO mimetic further comprises a hydrophilic polymer covalently linked to the peptide.

[0088] Embodiment 1(d) is the method of embodiment 1(c), wherein the hydrophilic polymer is any one of: i) polyethylene glycol (PEG), ii) polypropylene glycol, iii) polylactic acid, or iv) polyglycolic acid.

[0089] Embodiment 1(e) is the m...

Embodiment 1

[0177] Example 1: Administration of Thrombopoietin Mimetics Preserves Vascular Function in Rat Prostate Irradiation Model of Erectile Dysfunction

[0178] Materials and methods

[0179] animal:

[0180] Thirty-five eight-week-old male Sprague Dawley rats were obtained from Charles River Laboratories (Malvern, PA) and were pair-housed under standard housing conditions. Animals were divided into 4 groups: saline / sham, saline RT, TPOm / sham, TPOm / RT. The Duke University School of Medicine Institutional Animal Care and Use Committee approved all animal work.

[0181] TPOm synthesis and treatment:

[0182] TPOm was synthesized by Janssen Pharmaceuticals as previously described (Knight et al., Int. J. Toxicol. 30(4):385-404 (2011)) and shipped as a lyophilized powder on dry ice to Duke University. TPOm was reconstituted in sterile saline, sterile filtered, aliquoted, and stored at -20°C until use. Ten minutes after RT, TPOm was administered as a single dose by subcutaneous inje...

Embodiment 2

[0202] Example 2: Evaluation of the effects of thrombopoietin mimetics on radiation-induced vascular permeability and leukocyte adhesion using a novel murine ear vein model

[0203] Materials and methods

[0204] animal

[0205] Flk1-mCherry mice were bred in the Duke University Breeding Core Facility (Larina et al., Anat. Rec. 292(3):333-41 (2009)). Throughout the experiment, male and female mice at least 8 weeks of age were transferred to an accessible facility and housed in groups. Vascular endothelial cells of Flk1-mCherry mice constitutively express mCherry, which facilitates intravital microscopy imaging and analysis. All animal work was approved by the Institutional Animal Care and Use Committee at Duke University School of Medicine.

[0206] ear irradiation

[0207]Mice were anesthetized by intraperitoneal injection of 80 / 8 mg / kg ketamine / xylazine. Mice were placed in a cylindrical lead jig (jig) that shielded the entire body except the pinna of the left ear, and ...

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Abstract

Methods of protecting vascular integrity in a subject exposed to a targeted radiation therapy are described. In particular, an effective amount of a thrombopoietin (TPO) mimetic, such as TPOm, is usedto protect vascular integrity following the radiation therapy.

Description

[0001] References to Sequence Listings Submitted Electronically [0002] This application contains a sequence listing. The file name of the sequence listing in ASCII format submitted electronically through EFS-Web is "Sequence Listing", the date of creation is July 24, 2018, and the size is 3.7kb. The sequence listing submitted via EFS-Web is part of this specification and is incorporated herein by reference in its entirety. technical field [0003] The present invention relates to methods of protecting vascular integrity, and more particularly, to methods of protecting vascular integrity in subjects exposed to targeted radiation therapy. The method includes administering to the subject an effective amount of a thrombopoietin (TPO) mimetic. Background technique [0004] Acute radiation syndrome (ARS), also known as radiation toxicity or radiation sickness, is caused by high doses of penetrating radiation irradiating the entire body (or parts of the body) within a short per...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/60A61K38/00A61P35/00
CPCA61K38/196A61K47/60A61N2005/1094A61K38/10A61K38/22A61P35/00A61N5/10
Inventor G·艾肯鲍姆A·托内利
Owner JANSSEN PHARMA NV
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