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EP-4342462-B1 - ACEBUTOLOL HYDROCHLORIDE FOR USE IN TREATING PSORIASIS

EP4342462B1EP 4342462 B1EP4342462 B1EP 4342462B1EP-4342462-B1

Inventors

  • SUN, LIANGDAN
  • ZHEN, Qi
  • CHEN, WEIWEI
  • WANG, YIRUI
  • LI, ZHUO

Dates

Publication Date
20260506
Application Date
20221222

Claims (4)

  1. The adrenoceptor beta 1 (ADRB 1) active inhibitor acebutolol hydrochloride (ACE) for use in a method for treating psoriasis.
  2. The ADRB1 active inhibitor ACE for use according to claim 1, wherein the ADRB1 active inhibitor ACE inhibits the abnormal activation of skin sympathetic nerves.
  3. The ADRB1 active inhibitor ACE for use according to claim 2, wherein the ADRB1 active inhibitor ACE inhibits the increase of norepinephrine caused by the abnormal activation of the skin sympathetic nerves.
  4. The ADRB1 active inhibitor ACE for use according to claim 1, wherein the ADRB1 active inhibitor ACE inhibits the secretion of interleukin 17 (IL-17) by γδT cells.

Description

TECHNICAL FIELD The invention relates to the technical field of dermatologic drugs, and more particularly to a use/application of an adrenoceptor beta 1 (ADRB1) active inhibitor in preparing a preparation or as a preparation for treating psoriasis. BACKGROUND Psoriasis is a chronic inflammatory skin disease characterized by infiltration of immune cells, epidermal hyperplasia, and abnormal differentiation of keratinocytes. Previous studies have found that keratinocytes and immune cells interact to produce cytokine networks, especially interleukin 17 (IL-17) family and its subsequent signal cascades, which drive the development of psoriasis. Psychological and neurological factors are one of inducements of pathogenesis and aggravation of psoriasis, and neuroendocrine is one of important functions of a skin peripheral nervous system. Psychological factors, as a stressor, mainly cause the activation of two major neuroendocrine systems, namely, the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic-adrenal medullary system (SAM), and cause the cascade reaction of neuroendocrine hormones and the release of proinflammatory cytokines. As psoriasis is related to the increased activity of a variety of proinflammatory cytokines, thereby further inducing or aggravating psoriasis. At present, studies have shown that IL17A/F is an important cytokine of effector cells of psoriasis, and the clinical use of biological agents targeting IL17A/F has a good therapeutic effect on psoriasis. However, the related biological agents have a high price and need to be used continuously in the late stage, so that the treatment cost is high and psoriasis cannot be eradicated. Therefore, a safe and effective preparation for treating psoriasis is necessary. B. Azzouz et al. (British Journal of Clinical Pharmacology, 2022, vol. 88(8), pages 3813-3818, DOI: 10.1111[bcp.15330) provides a restrospective analysis of psoriasis risk after beta-blocker exposure. K. H. Basavaraj et al. (International Journal of Dermatology, 2010, vol. 49 (12), pages 1351-1361, DOI: 10.1111/J.1365-4632.2010.04570.X) discloses that psoriasis is a common skin disorder; knowledge of the factors that may induce, trigger, or exacerbate the disease is of primary importance in clinical practice. Drug intake is a major concern in this respect, as new drugs are constantly being added to the list of factors that may influence the course of this disease. Drug ingestion may result in exacerbation of pre-existing psoriasis, in induction of psoriatic lesions on clinically uninvolved skin in patients with psoriasis, or in precipitation of the disease in persons without family history of psoriasis or in predisposed individuals. In view of their relationship to drug-provoked psoriasis, therapeutic agents may be classified as drugs with strong evidence for a causal relationship to psoriasis, drugs about which there are considerable but insufficient data to support the induction or aggravation of the disease, and drugs that are occasionally reported to be associated with aggravation or induction. This review focuses on the most common causative agents for drug-induced, drug-triggered, or drug-aggravated psoriasis, such as β-blockers, lithium, synthetic antimalarial drugs, nonsteroidal anti-inflammatory agents, and tetracyclines, and the mechanisms of action of these drugs in the pathogenesis of psoriasis. SUMMARY In view of the above problems, a purpose of the invention is to provide an adrenoceptor beta 1 (ADRB 1) active inhibitor for use in a method for treating psoriasis. The ADRB1 activity inhibitor acebutolol hydrochloride, abbreviated ACE, can effectively inhibit the increase of norepinephrine (NE, also referred to as noradrenaline) caused by abnormal activation of skin sympathetic nerve, and stimulate the secretion of interleukin 17 (IL-17) of gamma delta (γδ) T cells (also referred to as T lymphocytes), thereby reducing the IL-17-mediated immune response at skin lesions in psoriasis and achieving the effect of treating psoriasis. In order to achieve the above purpose, the invention may adopt technical solutions as follows. In an aspect, the invention provides acebutolol hydrochloride for use in a method for treating psoriasis. Specifically, in the invention, IL-17-producing γδT cells are activated by ADRB 1, which indicates that psychological and neurological factors can be used as inducements of pathogenesis and aggravating of psoriasis, provides a potential target for treating psoriasis, and provides help for research and development of drugs for treating psoriasis. It should be noted that an ADRB1 activity inhibitor is known in the art to be a reagent that can inhibit ADRB1 activity, which may be a chemical reagent, such as acebutolol hydrochloride (ACE); and may also be a biological reagent, such as clustered regularly interspaced palindromic repeats-associated protein 9 (CRISPR-Cas9) reagent. According to the present invention, the ADRB1 activity inhibitor for u