Unlock instant, AI-driven research and patent intelligence for your innovation.

Cerdulatinib-containing topical skin pharmaceutical compositions and uses thereof

A technology of sadutinib and its composition, applied in the topical skin pharmaceutical composition containing sadutinib and its application field

Pending Publication Date: 2020-10-23
德玛万科学有限公司
View PDF10 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, concerns about appearance and ethnic identity are significant issues for many affected individuals

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
  • Cerdulatinib-containing topical skin pharmaceutical compositions and uses thereof
  • Cerdulatinib-containing topical skin pharmaceutical compositions and uses thereof
  • Cerdulatinib-containing topical skin pharmaceutical compositions and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0204] Example 1: In vitro potency and selectivity of DMVT-502

[0205] In Vitro Pharmacology Studies The activity and potency of DMVT-502 have been evaluated against a panel of purified kinase assays, followed by specific cellular potency assays against Syk, JAK1, JAK2, JAK3 and Tyrosine Kinase 2 (Tyk2). The efficacy of DMVT-502 was assessed in primary cells and whole blood stimulated with various cytokines to measure JAK / signal transducer and activator of transcription (STAT)-specific pathway responses.

[0206] Efficacy against Syk, JAK1 , JAK2, JAK3, and Tyk2 was tested using the DiscoverRx cell platform and compared to tofacitinib and the JAK1 / 2 selective inhibitor ruloxitinib. Table 1 shows significant potency against Syk, JAK1, and Tyk2, with diminished potency against cellular JAK2 and JAK3.

[0207] Table 1. Potency of DMVT-502 against Syk, JAK1, JAK2, JAK3, and Tyk2 in the DiscoverRx cell platform

[0208]

[0209] Abbreviation: IC 50 , 50% inhibitory concentra...

Embodiment 2

[0212] Example 2: Inhibition of Cytokine Signaling in Peripheral Blood Mononuclear Cell Cultures and Human Whole Blood

[0213] Human primary cells isolated from healthy volunteers were stimulated with various cytokines to measure JAK / STAT-dependent or JAK / STAT-independent signaling and functional responses following exposure to DMVT-502. Peripheral blood mononuclear cells were prepared from human whole blood and incubated with various concentrations of DMVT-502 to elicit JAK / STAT signaling prior to stimulation with appropriate cytokines. Cells were fixed, permeabilized, and subsequently stained with cell-specific lineage and phosphorylated STAT antibodies for intracellular phosphorylation flow cytometry to determine the effect of DMVT-502 on cytokine-mediated STAT phosphorylation. Data from these assays confirmed that DMVT-502 is a potent inhibitor of JAK1 / JAK3-dependent signaling pathways, where IC in T cells and monocytes 50 Values ​​are less than 0.2 μM.

[0214] Cytokin...

Embodiment 3

[0216] Example 3: Skin Penetration Study

[0217] A study was conducted to evaluate the in vitro skin penetration and penetration of sedutinib. The studies included full in vitro skin permeation and permeation experiments for formulations containing sedutinib.

[0218] Freshly excised human skin (cut with a dermatome to a thickness of 500 ± 50 μm) from one skin donor was mounted on the MedFlux-HT TM Between the donor and acceptor compartments of the diffusion cell (~1 cm exposed surface area for each replicate) 2 ). Apply approximately 10 mg of sedutinib formulation to the skin to achieve ~10 mg / cm 2 dosage. Adjust the pump of the MedFlux system to maintain a continuous receiver fluid flow rate of approximately 10 μL / min (600 μL / hr) just below the skin. Receiver fluid was automatically collected into 96-well plates at 2-hour intervals over the course of 24 hours and analyzed using LC-MS / MS analysis.

[0219] After the 24-hour in vitro drug penetration test, the residual ...

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
molecular weightaaaaaaaaaa
molecular weightaaaaaaaaaa
molecular weightaaaaaaaaaa
Login to View More

Abstract

Embodiments of topical formulations for administering cerdulatinib or a pharmaceutically acceptable salt, hydrate or solvate thereof are disclosed. Embodiments of methods for preparing the topical formulations are also disclosed. The disclosed formulations are suitable for the treatment of dermatologic conditions such as atopic dermatitis.

Description

[0001] field of invention [0002] The present disclosure relates to topical formulations containing cerdulatinib and methods of using the formulations to treat skin disorders such as atopic dermatitis, alopecia areata, vitiligo, and chronic urticaria. [0003] Background of the invention [0004] Atopic dermatitis (AD) is clinically defined as a chronic intermittent disease of the skin characterized by intense pruritic (itching) and inflammatory eczematous lesions. It is one of the most common chronic diseases, affecting 10% to 20% of the population in developed countries [Deckers, 2012; Williams, 2008]. AD occurs more commonly in children (affecting 15%-30% of the pediatric population) [Williams, 2006], while approximately 10% of adults are affected [Silverberg, 2013]. In the pediatric population, approximately 60% of patients present in the first year of life [Illi, 2004; Garmhausen, 2013], and approximately 85% of patients present before the age of 5 years [Bieber, 2008]. ...

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
Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K47/08A61K47/10A61K9/06A61K47/38A61K31/506
CPCA61K9/0014A61K47/08A61K47/10A61K9/06A61K47/38A61K31/506A61K45/06A61P17/00A61P17/14
Inventor C·R·G·伊文斯C·R·史蒂文森M·B·布朗
Owner 德玛万科学有限公司