US-12616709-B2 - Pharmaceutical composition for treating sepsis and use thereof

US12616709B2US 12616709 B2US12616709 B2US 12616709B2US-12616709-B2

Abstract

The present disclosure provides a pharmaceutical composition for treating sepsis and use thereof, belonging to the technical field of chemical drugs. The present disclosure provides a three-component pharmaceutical composition including hydroxysafflower yellow A (HSYA), paeoniflorin, and albiflorin. The present disclosure further provides a seven-component pharmaceutical composition including HSYA, paeoniflorin, albiflorin, oxypaeoniflorin, senkyunolide I, salvianic acid A sodium (SAAS), and ferulic acid. In the present disclosure, it is verified at the cell level and the animal level that both two groups of the pharmaceutical compositions have an efficacy of effectively treating sepsis. Meanwhile, drug toxicity experiments show that the two groups of the pharmaceutical compositions both are safe. The pharmaceutical composition is an active ingredient of the Xuebijing Injection, which can be used for the clinical treatment of sepsis.

Inventors

Yang Yu
Jianli Wang
Chunliang Jiang
Xiangcheng Wang
Yukun LI
Baoqi Li
Guiping Zhang
KAI DONG
Xiaoqing YAO

Assignees

TIANJIN CHASE SUN PHARMACEUTICAL CO., LTD.

Dates

Publication Date: 20260505
Application Date: 20210323
Priority Date: 20210301

Claims (10)

1 . The pharmaceutical composition for treating sepsis consisting of the following seven components as active ingredients: hydroxysafflor yellow A (HSYA) with a structural formula shown in formula I, paeoniflorin with a structural formula shown in formula II, and albiflorin with a structural formula shown in formula III; oxypaeoniflorin with a structural formula shown in formula IV, senkyunolide I with a structural formula shown in formula V, salvianic acid A sodium (SAAS) with a structural formula shown in formula VI, and ferulic acid with a structural formula shown in formula VII; wherein the HSYA, the paeoniflorin, and the albiflorin are present in a mass ratio of (1-100):(1-100):(0.1-10); and the HSYA, the paeoniflorin, the albiflorin, the oxypaeoniflorin, the senkyunolide I, the SAAS, and the ferulic acid are present in a mass ratio of (1-100):(1-100):(1-10):(0.1-10):(0.1-10):(0.1-10):(0.01-1);
2 . The pharmaceutical composition for treating sepsis according to claim 1 , wherein the HSYA, the paeoniflorin, the albiflorin, the oxypaeoniflorin, the senkyunolide I, the SAAS, and the ferulic acid are present in a mass ratio of (1-100):(1-100):(1-10):(1-10):(1-10):(1-10):(0.1-1).
3 . A pharmaceutical composition for treating sepsis, consisting of the following three components as active ingredients: hydroxysafflor yellow A (HSYA) with a structural formula shown in formula I, paeoniflorin with a structural formula shown in formula II, and albiflorin with a structural formula shown in formula III; wherein the HSYA, the paeoniflorin, and the albiflorin are present in a mass ratio of (1-100):(1-100):(0.1-10);
4 . The pharmaceutical composition for treating sepsis according to claim 3 , wherein the HSYA, the paeoniflorin, and the albiflorin are present in a mass ratio of (1-100):(1-100):(1-10).
5 . A method for treating sepsis, comprising: administering a drug prepared from the pharmaceutical composition according to claim 1 to a patient in need.
6 . A method for treating sepsis, comprising: administering a drug prepared from the pharmaceutical composition according to claim 1 to a patient in need, wherein the pharmaceutical composition comprises seven active compounds of the HSYA, the paeoniflorin, the albiflorin, the oxypaeoniflorin, the senkyunolide I, the SAAS, and the ferulic acid, 6 mg/kg to 600 mg/kg of the HSYA, 6 mg/kg to 600 mg/kg of the paeoniflorin, 0.6 mg/kg to 60 mg/kg of the albiflorin, 0.6 mg/kg to 60 mg/kg of the oxypaeoniflorin, 0.6 mg/kg to 60 mg/kg of the senkyunolide I, 0.6 mg/kg to 60 mg/kg of the SAAS, and 0.06 mg/kg to 6 mg/kg of the ferulic acid are used.
7 . A method for treating sepsis, comprising: administering a drug prepared from the pharmaceutical composition according to claim 2 to a patient in need.
8 . A method for treating sepsis, comprising: administering a drug prepared from the pharmaceutical composition according to claim 3 to a patient in need.
9 . The method for treating sepsis according to claim 8 , wherein the pharmaceutical composition comprises three active compounds of the HSYA, the paeoniflorin, and the albiflorin, 6 mg/kg to 600 mg/kg of the HSYA, 6 mg/kg to 600 mg/kg of the paeoniflorin, and 0.6 mg/kg to 60 mg/kg of the albiflorin are used.
10 . A method for treating sepsis, comprising: administering a drug prepared from the pharmaceutical composition according to claim 4 to a patient in need.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a U.S. National Phase Application under 35 U.S.C. § 371 of International Application No. PCT/CN2021/082244, filed on Mar. 23, 2021, which claims priority to Chinese Patent Application No. 202110225428.6, filed on Mar. 1, 2021, and titled “PHARMACEUTICAL COMPOSITION FOR TREATING SEPSIS AND USE THEREOF,” the contents of which is incorporated by reference in its entirety. TECHNICAL FIELD The present disclosure belongs to the technical field of chemical drugs, and in particular relates to a pharmaceutical composition for treating sepsis and use thereof. BACKGROUND Sepsis is a fatal organ dysfunction caused by a dysregulated response to an infected host. The sepsis causes a dangerous condition and a high fatality rate, and is the main cause of death of the severe patients. Antibiotics, antivirals, and vasopressors have been used in the traditional treatment of sepsis for many years. However, there are not enough specific drugs targeting the pathogenesis of sepsis in clinical practices. Timely remedy of systemic inflammatory response, coagulation dysfunction, and immune dysfunction during the progress of sepsis has become an important topic to be address in the research and development of therapeutic drugs for the sepsis. This can help to restore a pro-inflammatory/anti-inflammatory dynamic balance in the body as soon as possible, and effectively improve the prognosis of patients. Xuebijing Injection is an intravenous injection. The Xuebijing Injection is based on the principle of syndrome differentiation of “Three syndromes and three methods” (namely. “toxin-heat syndrome” with “heat-clearing and detoxifying”. “blood stasis syndrome” with “activating blood circulation and removing blood stasis”, and “acute deficiency syndrome” with “strengthening and consolidating body resistance”), and under the guidance of a theory “combining the treatment of pathogenic bacteria, toxin, and inflammation”. The Xuebijing Injection is developed with a “Xuefu Zhuyu Decoction (decoction for repelling blood stasis in blood vessels)” recorded in the “Yilin Gaicuo (Correction on Errors in Medical Classics)” written by Qingren Wang of the Qing Dynasty. This injection is prepared from five Chinese medicinal materials of Carthamus tinctorius, Radix paeoniae rubra, Rhizoma chuanxiong, Radix salviae miltiorrhizae, and Radix angelicae sinensis through modern processes such as extraction, refining, drying, and blending. This injection is suitable for sepsis/infection-induced systemic inflammatory response syndrome (SIRS), and can also be used in the treatment of organ dysfunction in multiple-organ dysfunction syndrome. However, the Xuebijing Injection is prepared from Chinese herbal medicines, and the main medicinal ingredients for sepsis are yet unclear. Therefore, it is still necessary to extract and refine various Chinese medicinal materials to prepare a pharmaceutical composition for treating sepsis. SUMMARY In view of this, an objective of the present disclosure is to provide a novel pharmaceutical composition for treating sepsis and use thereof. The pharmaceutical composition is directly consisting of active compounds for treating the sepsis, thus avoiding cumbersome extraction steps of traditional Chinese medicines. Moreover, in this way, the components of the pharmaceutical composition are simplified and the efficacy of an obtained product is improved. The present disclosure provides a pharmaceutical composition for treating sepsis, including hydroxysafflor yellow A (HSYA) with a structural formula shown in formula I, paeoniflorin with a structural formula shown in formula II, and albiflorin with a structural formula shown in formula III; where HSYA, paeoniflorin, and albiflorin are present in a mass ratio of (1-100):(1-100):(0.1-10); Preferably, HSYA, paeoniflorin, and albiflorin are present in a mass ratio of (1-100):(1-100):(1-10). Preferably, the pharmaceutical composition for treating sepsis further includes oxypaeoniflorin with a structural formula shown in formula IV, senkyunolide I with a structural formula shown in formula V, salvianic acid A sodium (SAAS) with a structural formula shown in formula VI, and ferulic acid with a structural formula shown in formula VII; where the HSYA, the paeoniflorin, the albiflorin, the oxypaeoniflorin, the senkyunolide I, the SAAS, and the ferulic are a mass acid present in ratio of (1-100):(1-100):(1-10):(0.1-10):(0.1-10):(0.1-10):(0.01-1); Preferably, the HSYA, the paeoniflorin, the albiflorin, the oxypaeoniflorin, the senkyunolide I, the SAAS, and the ferulic acid are present in a mass ratio of (1-100):(1-100):(1-10):(1-10):(1-10):(1-10):(0.1-1). The present disclosure further provides use of the pharmaceutical composition in preparation of a drug for treating sepsis. Preferably, the pharmaceutical composition is used in preparing a drug for treating sepsis by inhibiting expressions of IL-6, Foxp3, CTLA-4, and/or HMGB1. Preferabl