阅读说明：本技术 四乙酰灯盏乙素苷元在治疗和预防脓毒症药物中的应用 (application of tetraacetylscutellarin aglycone in medicine for treating and preventing sepsis ) 是由 张祎 倪广惠 王睿睿 饶高雄 黄丰 于 2018-06-07 设计创作，主要内容包括：本发明公开了四乙酰灯盏乙素苷元(I)在治疗和预防脓毒症药物中的应用。通过实验证明,四乙酰灯盏乙素苷元对脓毒症模型小鼠的生存保护作用,能降低脓毒症模型小鼠血清IL-1β和IL-6水平。四乙酰灯盏乙素苷元可能通过调节IL-1β及IL-6的表达抑制炎症而发挥对脓毒症的保护作用。四乙酰灯盏乙素苷元具有治疗和预防脓毒症药物应用前景。<Image he="175" wi="275" file="100004_DEST_PATH_IMAGE002.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(The invention discloses application of tetraacetylscutellarin aglycone (I) in medicines for treating and preventing sepsis. Experiments prove that the tetraacetylscutellarin aglycone has the survival protection effect on the sepsis model mouse and can reduce the serum IL-1 beta and IL-6 levels of the sepsis model mouse. The tetraacetyl scutellarin aglycone can play a role in protecting the sepsis by regulating the expression of IL-1 beta and IL-6 to inhibit inflammation. Tetraacetylscutellarin aglycone for treating and preventingThe sepsis medicine has application prospect.)

1. Application of tetraacetyl scutellarin aglycone (I) in preparation of medicines for treating and preventing sepsis

。

2. The use according to claim 1, wherein sepsis is sepsis and its associated diseases such as acute lung injury, acute liver injury, acute kidney injury, endotoxemia and septic shock.

3. A medicament for the treatment and prevention of sepsis, characterized in that it comprises tetraacetylscutellarin (I) according to claim 1.

4. The medicament of claim 3, wherein the dosage form is an oral dosage form or an intravenous injection.

Technical Field

The invention belongs to the technical field of medicines, and particularly relates to application of tetraacetylscutellarin aglycone in medicines for treating and preventing sepsis.

Background

Sepsis refers to a systemic inflammatory response induced by infection that can lead to shock, Multiple Organ Dysfunction Syndrome (MODS), and even death. There are 1800 ten thousand global estimates, the incidence is: 3/1000, and increased at a rate of 1.5% per year. The overall hospital fatality rate of patients with sepsis is 28.6 percent, while the fatality rates of patients with severe sepsis and sepsis shock are 25 to 30 percent and 40 to 70 percent respectively, and 1400 million people die every day in the world. Sepsis patients are very costly to treat, accounting for 40% of ICU consumption. Sepsis has now become a leading cause of death in patients in non-cardiac intensive care units.

The pathogenic microorganism can be classified into typhoid fever and epidemic febrile disease in traditional Chinese medicine, and the pathogenesis of the pathogenic microorganism is that macrophages, neutrophils, endothelial cells and the like activated by pathogenic microorganism release a large amount of inflammatory mediators, superoxide anions and the like to cause endothelial cell injury, blood coagulation dysfunction and the like, so that microcirculation is hindered, and finally, multiple organ dysfunction is caused. Proinflammatory and anti-inflammatory, pathogenic and rabbit diseases, imbalance and compensation, etc. are all throughout the disease process. The traditional western medicine has the limitation of single-target treatment, the traditional Chinese medicine accumulates abundant experience in the aspect of treating sepsis, and the medicines with the functions of promoting blood circulation, removing blood stasis, cooling blood, removing blood stasis and the like are widely applied to clinic, and the medicines can dredge qi and blood in collaterals, reduce the accumulation of toxic factors and improve the warm-up nourishing of various viscera, thereby having extremely important significance in preventing and treating sepsis. Therefore, the development of the medicine for preventing and treating sepsis based on the traditional Chinese medicine has application prospect.

Erigeron breviscapus is erigeron breviscapus of CompositaeErigeron breviscapus (Vant.) Hand.-mazz]Dried herbs, also called erigeron breviscapus and east chrysanthemumMainly distributed in the southwest area of China, especially in Yunnan. It is recorded in Dian nan Ben Cao (materia Medica of Dian), the Chinese pharmacopoeia (1977) edition. Erigeron breviscapus is cold in nature, slightly bitter, sweet and warm in flavor, and has the effects of removing toxic substances, dispelling wind and removing dampness, promoting blood circulation by removing blood stasis, clearing and activating the channels and collaterals, diminishing inflammation and relieving pain, wherein scutellarin is the main active ingredient of the erigeron breviscapus. Scutellarin has effects of dilating blood vessel, reducing blood viscosity, improving microcirculation, and preventing and treating thrombosis. Researches show that the compound has a protective effect on ischemia reperfusion injury of pancreas, cardiac muscle, brain tissue and the like of rats and has a certain protective effect on sepsis model rats caused by LPS.

Breviscapine has poor water solubility, water solubility of only 0.16 mg/mL and poor fat solubility, logP in PBS with pH of 4.2 is-2.56, the Beagle dog has absolute bioavailability of only (0.40 +/-0.19)%, while the intravenous injection elimination half-life of the domestic dog is only (52 +/-29) min, and the physicochemical property and the in vivo behavior limit the clinical application of the breviscapine. At present, common tablets, granules, injections, powder injections and the like exist on the market, so that the novel formulation of breviscapine is developed, the oral bioavailability of the breviscapine is improved or the half-life period of the breviscapine in vivo is prolonged, and the breviscapine has great market value. In recent years, the development of new formulations of breviscapine is getting hotter, and the published invention patent is up to 59, relating to injection, liposome, phospholipid complex, rapidly disintegrating oral tablet, sublingual tablet, sustained release pellet, osmotic pump controlled release preparation, cyclodextrin inclusion compound, drop pill, self-emulsifying agent and the like. In addition, the chemical structure of scutellarin is modified to improve the physicochemical property of scutellarin, so that the bioavailability of scutellarin is improved. In the process of carrying out structural modification on scutellarin, the inventors find that the tetraacetyl scutellarin aglycone has good treatment effect on sepsis.

Disclosure of Invention

The invention aims to provide application of tetraacetylscutellarin aglycone (I) in medicines for treating and preventing sepsis.

The purpose of the invention is realized as follows:

Application of tetraacetyl scutellarin aglycone (I) in medicines for treating and preventing sepsis is provided.

sepsis refers to sepsis and its related diseases, such as acute lung injury, acute liver injury, acute kidney injury, endotoxemia, septic shock, etc.

A medicine for treating and preventing sepsis comprises tetraacetyl scutellarin aglycone (I).

the dosage form is oral dosage form or intravenous injection.

The invention has the advantages that:

1. The experimental research provided by the invention proves that the tetraacetyl scutellarin aglycone (I) can reduce the death rate of a sepsis model mouse and has stronger survival protection effect;

2. The invention provides application of tetraacetylscutellarin aglycone (I), namely application of tetraacetylscutellarin aglycone (I) in preparation of a medicament for treating sepsis, and the tetraacetylscutellarin aglycone can reduce the level of inflammatory factors in a sepsis model mouse.

Drawings

FIG. 1 is the chemical structural formula of the tetraacetyl scutellarin aglycone (I) of the present invention;

FIG. 2 shows the CLP model ligation site and its schematic view;

FIG. 3 shows the survival protection effect of tetraacetylscutellarin on septic mice;

FIG. 4 is a graph of the effect of tetraacetylscutellarin aglycone on serum IL-1 β levels in septic mice;

FIG. 5 is a graph of the effect of tetraacetylscutellarin aglycone on serum IL-6 levels in septic mice.

Detailed Description

The present invention is further illustrated but not limited in any way by the following examples, and any modifications made thereto are intended to fall within the scope of the present invention.

Application of tetraacetyl scutellarin aglycone (I) in preparing medicine for treating and preventing sepsis is provided.

sepsis refers to sepsis and its related diseases, such as acute lung injury, acute liver injury, acute kidney injury, endotoxemia, septic shock, etc.

A medicine for treating and preventing sepsis comprises tetraacetyl scutellarin aglycone (I).

The dosage form is oral dosage form or intravenous injection.