WO2023124620A1 - Use of c. minuta in preparation of medication for treating and/or preventing hyperuricemia-related diseases - Google Patents

Use of c. minuta in preparation of medication for treating and/or preventing hyperuricemia-related diseases Download PDF

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WO2023124620A1
WO2023124620A1 PCT/CN2022/132718 CN2022132718W WO2023124620A1 WO 2023124620 A1 WO2023124620 A1 WO 2023124620A1 CN 2022132718 W CN2022132718 W CN 2022132718W WO 2023124620 A1 WO2023124620 A1 WO 2023124620A1
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minuta
christensenella
group
preparation
uric acid
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陈嘉莉
白卫滨
李海威
肖宇航
张文宝
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暨南大学
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents

Definitions

  • the invention relates to the technical field of biomedicine, in particular to the application of Christensenella minor in the preparation of medicines for treating and/or preventing diseases related to hyperuricemia.
  • Uric acid is the terminal metabolite of human purine compounds, and disorders of purine metabolism can lead to hyperuricemia.
  • Hyperuricemia refers to the state of normal purine diet, the fasting blood uric acid level on two different days is higher than 420 ⁇ mol/L for men and higher than 360 ⁇ mol/L for women, which is called hyperuricemia.
  • the blood uric acid level exceeds the saturation of joint monosodium urate and precipitates and deposits in peripheral joints and surrounding tissues, it is called gout. Therefore, hyperuricemia is the basis of gout, but it is not enough to cause gout. Gout occurs only when urate deposits in body tissues and causes damage. Therefore, reducing uric acid level is an effective means to treat or prevent diseases related to high uric acid.
  • the technical problem to be solved by the present invention is to provide the application of Christensenella minor in the preparation of medicines for the treatment and/or prevention of diseases related to hyperuricemia, which can significantly reduce the level of uric acid.
  • Christensenellaceae belongs to Firmicutes, widely exists in human and animal intestinal mucosa.
  • Christensenella minuta (C.minuta) is the currently discovered species of Christensenellaceae.
  • Christensenella minor was originally isolated from the feces of a healthy Japanese male and was first definitively described as a species in the Christensenaceae in 2012. Oxygen-type gram-negative brevibacteria.
  • C.minuta has a potential relationship with body weight and inflammatory bowel diseases such as Crohn's disease, ulcerative colitis and irritable bowel syndrome.
  • results are all derived from the changes of C.minuta at the 16s or metagenomic sequencing level in the disease state, lacking mechanism exploration and relevant strong evidence.
  • the latest related literature reported that dietary supplementation with C.minuta DSM 22607 could inhibit relevant inflammatory factors and alleviate enteritis in the mouse model of DNBS-induced acute colitis and the rat model of TNBS-induced acute colitis.
  • the invention provides an application of Christensenella minuta, its cell components, metabolites and/or secretions in the preparation of medicines for treating and/or preventing diseases related to high uric acid.
  • cell components include stem cells, the culture medium containing the cells, and various chemical components that make up the cells; metabolites include intermediate metabolites and final metabolites in metabolism, etc.; secretions include enzymes, antibodies, and hormones.
  • the Christensenella minuta is Christensenella minuta DSM22607 from the German Culture Collection of Microorganisms (DSMZ).
  • the drug is Christensenella minor, its cellular components, metabolites and/or secretions, and a pharmaceutically acceptable carrier.
  • the pharmaceutically acceptable carrier can be sugars, such as lactose, glucose and sucrose; starch, such as corn starch and potato starch; cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and formazan base cellulose; malt; gelatin; vegetable oil, peanut oil, corn oil, cocoa butter, and sesame oil; polyalcohols, such as glycerin, sorbitol mannitol; flavoring agents; tableting agents; stabilizers; isotonic saline solutions, such as normal saline ; Phosphate buffered saline;
  • the dosage form of the drug is an oral preparation or an injection preparation.
  • the oral preparation is tablet, capsule, granule, concentrated pill or liquid.
  • tablets are mainly oral tablets, buccal tablets, sublingual tablets, buccal patches, chewable tablets, dispersible tablets, effervescent tablets, vaginal tablets, immediate-release or sustained-release or controlled-release tablets, and enteric-coated tablets, etc.
  • Capsules include hard capsules and soft capsules; granules include soluble granules, suspension granules, effervescent granules, enteric-coated granules, sustained-release granules and controlled-release granules, etc.; concentrated pills include concentrated water pills, concentrated honey pills and concentrated water honey pills; liquid Dosages include oral solutions, ear solutions, ophthalmic solutions and external solutions, and the present invention is not particularly limited thereto.
  • the injection preparation is liquid injection, powder for injection or tablet for injection.
  • liquid injections include solution (aqueous or non-aqueous) injections, suspension injections and emulsion injections, etc.; powders for injections include sterile powders and freeze-dried powders, etc.; Printing and machine pressing, etc., the present invention is not particularly limited to this.
  • the invention provides a new application of Christensenella minor for preparing medicines for treating and/or preventing diseases related to high uric acid.
  • the experimental results show that the Christensenella minor provided by the present invention can obviously inhibit the increase of uric acid value of the model group mice fed a high-sugar and high-fat diet, and its uric acid value level is equivalent to that of a control group mouse fed a normal diet. There is a significant difference (p ⁇ 0.05).
  • Figure 1 shows the effect of Christensenella minuta intervention on obesity;
  • A phenotypic changes in body shape (left: Control; middle: Model; right: C.minuta);
  • B body weight Change; different lowercase letters indicate significant differences between groups (p ⁇ 0.05), and the same lowercase letters indicate no significant differences between groups (p>0.05);
  • Figure 2 shows the effect of Christensenella minuta intervention on blood sugar;
  • A dynamic changes of blood sugar index in 0-12 weeks;
  • B blood sugar in week 12. Labeling with different lowercase letters indicates significant difference between groups (p ⁇ 0.05), and marking with the same lowercase letter indicates no significant difference between groups (p>0.05);
  • Figure 3 is the effect of Christensenella minuta intervention on glucose metabolism in the body; (A) dynamic changes in blood glucose in glucose tolerance test; (B) blood glucose under the curve of blood glucose curve. Labeling with different lowercase letters indicates significant difference between groups (p ⁇ 0.05), and marking with the same lowercase letter indicates no significant difference between groups (p>0.05);
  • the invention discloses an application of Christensenella minor in the preparation of medicines for treating and/or preventing diseases related to high uric acid.
  • Those skilled in the art can refer to the content of this article to appropriately improve the process parameters to achieve.
  • all similar replacements and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention.
  • the method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously make changes or appropriate changes and combinations to the method and application herein without departing from the content, spirit and scope of the present invention to realize and apply the present invention Invent technology.
  • Experimental animals C57BL/6JNifdc male mice, purchased from Zhejiang Weitong Lihua Experimental Animal Technology Co., Ltd. (certificate number: 20210728Abzz0619000723). The animals were reared adaptively in the Experimental Animal Center of Jinan University with a light time of 12 hours alternating between day and night, a temperature of 20-25°C, and a relative humidity of 50 ⁇ 5%, and free feeding. All experimental operations were carried out in accordance with the relevant requirements of the "Jinan University Experimental Animal Ethics Committee".
  • mice were randomly divided into 4 groups by weight stratification method, namely Control group, Model group, C.minuta group and metformin group.
  • a high-sugar and high-fat diet model was established, and fructose aqueous solution was prepared with pure water and given to the animals in the Model group, C. The experiment is over.
  • mice in the C.minuta group and the metformin group began to be intervened four weeks after the establishment of the model, and the intervention lasted until the end of the experiment.
  • the Control group and the Model group were given the corresponding volume of water, while the C. things.
  • mice in the Control group, the Model group and the C.minuta group were all weighed on the electronic balance at the 0th day, the fourth week, the eighth week, and the twelfth week of modeling. At the same time, the body shape of the mice was photographed and recorded, and the degree of obesity was calculated to evaluate the obesity of the mice.
  • Obesity (actual weight - standard weight) ⁇ standard weight ⁇ ⁇ 100%
  • the obesity degree is within ⁇ 10%, it is judged as normal and moderate; if the obesity degree exceeds 10%, it is judged as overweight; if the obesity degree exceeds 20%-30%, it is judged as mildly obese; if the obesity degree exceeds 30%-50%, it is judged as Moderately obese; obesity over 50% and above, judged as severe obesity; obesity below -10%, judged as underweight; obesity below -20% above, judged as emaciated.
  • mice in the Control group, the Model group and the C.minuta group were taken blood from the tail vein, and the blood glucose was tested with a blood glucose meter and blood glucose test paper and recorded and analyzed.
  • mice in the Control group, the Model group and the C.minuta group were intraperitoneally injected with a dose of 2g/kg of glucose solution. 0.1mL. Blood glucose levels of the mice were measured by taking blood from the tail vein at 0 minutes, 30 minutes, 60 minutes, and 120 minutes after the glucose injection.
  • mice After fasting and drinking for 6 hours, blood was collected from mice in all groups by taking blood from the eye sockets. After the blood was allowed to stand at room temperature for 30 minutes, it was centrifuged at 3000 rpm/min at 4°C for 15 minutes. Store at -80°C until use. Subsequently, the serum biochemical indicators CHO, TG, and UA were tested and recorded and analyzed by the automatic multifunctional animal biochemical analyzer (Indiko Plus) of Thermo Fisher Company.
  • the present invention has successfully constructed a high-sugar and high-fat diet model.
  • the Model group mice were hypertrophied and their body weight increased significantly, as shown in Figure 1.
  • the effect of Christensenella minuta intervention on obesity which can be diagnosed in mice by calculating the degree of obesity.
  • the mice in the Model group also had abnormal blood sugar index, as shown in Figure 2 and Table 1.
  • Figure 2 shows the effect of Christensenella minuta intervention on blood sugar
  • Table 1 shows the blood sugar levels of the mice. and AUC blood sugar index; further analysis of blood sugar tolerance found that the mice in the Model group had abnormal glucose metabolism, which could be diagnosed as diabetes, as shown in Figure 3.
  • Figure 3 shows the effect of Christensenella minuta intervention on the body Effects on glucose metabolism.
  • mice in the Model group and the metformin group have symptoms of hypercholesterolemia accompanied by atherosclerosis and a high risk of gout.
  • the intervention of Christensenella minuta can significantly and effectively reduce body weight, blood sugar, serum total triglycerides, serum uric acid, and abnormal glucose metabolism.
  • Metformin is recognized as a drug for the treatment of diabetes. The results showed that the reduction effect of serum total triglyceride and serum uric acid in the mice of C.minuta group was significantly better than that of metformin group.

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Abstract

Provided is a use of C. minuta in preparation of a medication for treating and/or preventing hyperuricemia-related diseases. A model mouse is used as a study object, and a control group, a model group, and a C. minuta group are set to study the effect of C. minuta in lowering body serum uric acid. The result shows that C. minuta can significantly inhibit the value of serum uric acid in a mouse of the C. minuta group, and the C. minuta group is significantly different from the model group, indicating that C. minuta has an obvious uric acid lowering effect and can mitigate symptoms such as hyperuricemia and gout diseases.

Description

一种小克里斯滕森氏菌在制备治疗和/或预防高尿酸相关疾病的药物中的应用Application of a kind of Christensenella minor in the preparation of medicines for treating and/or preventing diseases related to high uric acid
本申请要求于2021年12月27日提交中国专利局、申请号为202111616053.2、发明名称为“一种小克里斯滕森氏菌在制备治疗和/或预防高尿酸相关疾病的药物中的应用”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。This application is required to be submitted to the Chinese Patent Office on December 27, 2021, the application number is 202111616053.2, and the title of the invention is "A Application of Christensenella minor in the Preparation of Drugs for the Treatment and/or Prevention of Hyperuric Acid-Related Diseases" The priority of the Chinese patent application of , the entire content of which is incorporated in this application by reference.
技术领域technical field
本发明涉及生物医药技术领域，具体是一种小克里斯滕森氏菌在制备治疗和/或预防高尿酸相关疾病的药物中的应用。The invention relates to the technical field of biomedicine, in particular to the application of Christensenella minor in the preparation of medicines for treating and/or preventing diseases related to hyperuricemia.
背景技术Background technique
尿酸是人类嘌呤化合物的终末代谢产物，嘌呤代谢紊乱会导致高尿酸血症。高尿酸血症是指在正常嘌呤饮食状态下，非同日两次空腹血尿酸水平男性高于420μmol/L，女性高于360μmol/L，即称为高尿酸血症。而当血尿酸水平超过关节单钠尿酸盐饱和度而析出沉积于外周关节及周围组织时，则称为痛风。因此高尿酸血症是痛风的发病基础，但不足以导致痛风，只有尿酸盐在机体组织中沉积下来造成损害时才会出现痛风。因此，降低尿酸值是治疗或预防高尿酸相关疾病的有效手段。Uric acid is the terminal metabolite of human purine compounds, and disorders of purine metabolism can lead to hyperuricemia. Hyperuricemia refers to the state of normal purine diet, the fasting blood uric acid level on two different days is higher than 420 μmol/L for men and higher than 360 μmol/L for women, which is called hyperuricemia. When the blood uric acid level exceeds the saturation of joint monosodium urate and precipitates and deposits in peripheral joints and surrounding tissues, it is called gout. Therefore, hyperuricemia is the basis of gout, but it is not enough to cause gout. Gout occurs only when urate deposits in body tissues and causes damage. Therefore, reducing uric acid level is an effective means to treat or prevent diseases related to high uric acid.
发明内容Contents of the invention
有鉴于此，本发明要解决的技术问题在于提供小克里斯滕森氏菌在制备治疗和/或预防高尿酸相关疾病的药物中的应用，小克里斯滕森氏菌能够显著降低尿酸水平。In view of this, the technical problem to be solved by the present invention is to provide the application of Christensenella minor in the preparation of medicines for the treatment and/or prevention of diseases related to hyperuricemia, which can significantly reduce the level of uric acid.
克里斯滕森菌科(Christensenellaceae)属于厚壁菌门，在人类和动物肠道黏膜中广泛存在。目前发现的克里斯滕森菌科菌种有Christensenella minuta(C.minuta)。小克里斯滕森氏菌(C.minuta)最初从一名健康日本男性的粪便中培育分离所得，并于2012年首次被确切描述为克里斯滕森科中的一个种，是一种严格厌氧型革兰氏阴性的短杆菌。基于16S rRNA基因序列分析，将其命名 为Christensenella minuta DSM 22607(Morotomi,Masami,Fumiko Nagai,and Yohei Watanabe."Description of Christensenella minuta gen.nov.,sp.nov.,isolated from human faeces,which forms a distinct branch in the order Clostridiales,and proposal of Christensenellaceae fam.nov."International journal of systematic and evolutionary microbiology 62.1(2012):144-149.)。2014年，发现C.minuta有高度遗传性，是人类最易遗传的一类细菌(Goodrich,Julia K.,et al."Human genetics shape the gut microbiome."Cell 159.4(2014):789-799.)。此后在不同人群和多项研究中，发现人体内克里斯滕森科相对丰度与身体质量指数(Body Mass Index,BMI)呈负相关(Waters,Jillian L.,and Ruth E.Ley."The human gut bacteria Christensenellaceae are widespread,heritable,and associated with health."BMC biology 17.1(2019):1-11.)。Christensenellaceae (Christensenellaceae) belongs to Firmicutes, widely exists in human and animal intestinal mucosa. Christensenella minuta (C.minuta) is the currently discovered species of Christensenellaceae. Christensenella minor (C.minuta) was originally isolated from the feces of a healthy Japanese male and was first definitively described as a species in the Christensenaceae in 2012. Oxygen-type gram-negative brevibacteria. Based on 16S rRNA gene sequence analysis, it was named Christensenella minuta DSM 22607 (Morotomi, Masami, Fumiko Nagai, and Yohei Watanabe."Description of Christensenella minuta gen.nov.,sp.nov.,isolated from human faeces,which forms a distinct branch in the order Clostridiales, and proposal of Christensenellaceae fam.nov."International journal of systematic and evolutionary microbiology 62.1(2012):144-149.). In 2014, it was found that C.minuta is highly heritable and is the most heritable type of bacteria in humans (Goodrich, Julia K., et al."Human genetics shape the gut microbiome." Cell 159.4(2014):789-799. ). Since then, in different populations and multiple studies, it has been found that the relative abundance of Christensen in the human body is negatively correlated with body mass index (Body Mass Index, BMI) (Waters, Jillian L., and Ruth E.Ley."The Human gut bacteria Christensenellaceae are widely spread, heritable, and associated with health." BMC biology 17.1(2019):1-11.).
目前大多研究发现，C.minuta丰度降低甚至缺失，与体重和炎症性肠病如克罗恩病、溃疡性结肠炎和肠易激综合征有潜在的关系。然而结果均源于疾病状态下C.minuta在16s或宏基因组测序水平的变化，缺少机制探讨和相关有力的证据。最新一篇相关文献报道了在DNBS诱导急性结肠炎的小鼠模型以及TNBS诱导急性结肠炎的大鼠模型中，膳食补充C.minuta DSM 22607，都可抑制相关炎症因子缓解肠炎，并未深入进行进一步的机制探讨(Kropp,Camille,et al."The Keystone commensal bacterium Christensenella minuta DSM 22607 displays anti-inflammatory properties both in vitro and in vivo."Scientific Reports 11.1(2021):1-12.)At present, most studies have found that the reduced or even absent abundance of C.minuta has a potential relationship with body weight and inflammatory bowel diseases such as Crohn's disease, ulcerative colitis and irritable bowel syndrome. However, the results are all derived from the changes of C.minuta at the 16s or metagenomic sequencing level in the disease state, lacking mechanism exploration and relevant strong evidence. The latest related literature reported that dietary supplementation with C.minuta DSM 22607 could inhibit relevant inflammatory factors and alleviate enteritis in the mouse model of DNBS-induced acute colitis and the rat model of TNBS-induced acute colitis. Further mechanism discussion (Kropp,Camille,et al."The Keystone commensal bacterium Christensenella minuta DSM 22607 displays anti-inflammatory properties both in vitro and in vivo."Scientific Reports 11.1(2021):1-12.)
申请人发现，小克里斯滕森氏菌能够显著抑制C.minuta组小鼠的血清尿酸值(UA)，与Model组达到显著性差异，表明小克里斯滕森氏菌具有明显的降尿酸效果，可以改善高尿酸血症或痛风疾病等高尿酸相关疾病的症状。The applicant found that Christensenella minor could significantly inhibit the serum uric acid value (UA) of mice in the C.minuta group, which was significantly different from that of the Model group, indicating that Christensenella minor had an obvious effect of lowering uric acid , can improve the symptoms of high uric acid-related diseases such as hyperuricemia or gout.
本发明提供了一种小克里斯滕森氏菌(Christensenella minuta)、其细胞成分、代谢物和/或分泌物在制备治疗和/或预防高尿酸相关疾病的药物中的应用。The invention provides an application of Christensenella minuta, its cell components, metabolites and/or secretions in the preparation of medicines for treating and/or preventing diseases related to high uric acid.
可以理解的是，细胞成分包括干细胞、包含该细胞的培养液和组成细胞的各种化学成分；代谢物包括新陈代谢中的中间代谢物和最终代谢物等；分泌物包括酶、抗体和激素等。It can be understood that cell components include stem cells, the culture medium containing the cells, and various chemical components that make up the cells; metabolites include intermediate metabolites and final metabolites in metabolism, etc.; secretions include enzymes, antibodies, and hormones.
在一个实施例中，所述小克里斯滕森氏菌为小克里斯滕森氏菌 (Christensenella minuta)DSM22607，来自德国微生物菌种保藏中心(DSMZ)。In one embodiment, the Christensenella minuta is Christensenella minuta DSM22607 from the German Culture Collection of Microorganisms (DSMZ).
在一个实施例中，所述药物为小克里斯滕森氏菌、其细胞成分、代谢物和/或分泌物以及药学上可接受的载体。In one embodiment, the drug is Christensenella minor, its cellular components, metabolites and/or secretions, and a pharmaceutically acceptable carrier.
其中，药学上可接受的载体可以是糖类，如乳糖、葡萄糖和蔗糖；淀粉，如玉米淀粉和土豆淀粉；纤维素及其衍生物，如羧甲基纤维素钠、乙基纤维素和甲基纤维素；麦芽；明胶；植物油、花生油、玉米油、可可油和芝麻油；多元醇，如甘油、山梨糖醇甘露醇；调味剂；压片剂；稳定剂；等渗盐溶液，如生理盐水；磷酸盐缓冲溶液；Among them, the pharmaceutically acceptable carrier can be sugars, such as lactose, glucose and sucrose; starch, such as corn starch and potato starch; cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and formazan base cellulose; malt; gelatin; vegetable oil, peanut oil, corn oil, cocoa butter, and sesame oil; polyalcohols, such as glycerin, sorbitol mannitol; flavoring agents; tableting agents; stabilizers; isotonic saline solutions, such as normal saline ; Phosphate buffered saline;
在一个实施例中，所述药物的剂型为口服制剂或注射制剂。In one embodiment, the dosage form of the drug is an oral preparation or an injection preparation.
在一个实施例中，所述口服制剂为片剂、胶囊、颗粒、浓缩丸或液剂。In one embodiment, the oral preparation is tablet, capsule, granule, concentrated pill or liquid.
例如，片剂以口服普通片为主，也有含片、舌下片、口腔贴片、咀嚼片、分散片、泡腾片、***片、速释或缓释或控释片与肠溶片等；胶囊包括硬胶囊和软胶囊；颗粒包括可溶颗粒、混悬颗粒、泡腾颗粒、肠溶颗粒、缓释颗粒和控释颗粒等；浓缩丸包括浓缩水丸、浓缩蜜丸和浓缩水蜜丸；液剂包括口服溶液剂、耳用溶液剂、眼用溶液剂和外用溶液剂，本发明对此并无特殊限制。For example, tablets are mainly oral tablets, buccal tablets, sublingual tablets, buccal patches, chewable tablets, dispersible tablets, effervescent tablets, vaginal tablets, immediate-release or sustained-release or controlled-release tablets, and enteric-coated tablets, etc. ; Capsules include hard capsules and soft capsules; granules include soluble granules, suspension granules, effervescent granules, enteric-coated granules, sustained-release granules and controlled-release granules, etc.; concentrated pills include concentrated water pills, concentrated honey pills and concentrated water honey pills; liquid Dosages include oral solutions, ear solutions, ophthalmic solutions and external solutions, and the present invention is not particularly limited thereto.
在一个实施例中，所述注射制剂为液体注射剂、注射用粉剂或注射用片剂。In one embodiment, the injection preparation is liquid injection, powder for injection or tablet for injection.
例如，液体注射剂包括溶液(水性或非水性)注射剂、悬液注射剂和乳浊液注射剂等；注射用粉剂包括无菌粉剂和冻干粉剂等；注射用片剂包括用无菌操作法制成的模印片和机压片等，本发明对此并无特殊限制。For example, liquid injections include solution (aqueous or non-aqueous) injections, suspension injections and emulsion injections, etc.; powders for injections include sterile powders and freeze-dried powders, etc.; Printing and machine pressing, etc., the present invention is not particularly limited to this.
本发明提供了一种小克里斯滕森氏菌用于制备治疗和/或预防高尿酸相关疾病的药物的新用途。实验结果表明，本发明提供的小克里斯滕森氏菌可明显抑制高糖高脂饮食的模型组小鼠的尿酸值升高，其尿酸值水平与正常饮食的对照组小鼠相当，数据均具有显著性差异(p＜0.05)。The invention provides a new application of Christensenella minor for preparing medicines for treating and/or preventing diseases related to high uric acid. The experimental results show that the Christensenella minor provided by the present invention can obviously inhibit the increase of uric acid value of the model group mice fed a high-sugar and high-fat diet, and its uric acid value level is equivalent to that of a control group mouse fed a normal diet. There is a significant difference (p<0.05).
附图说明Description of drawings
图1为小克里斯滕森氏菌(Christensenella minuta)干预对肥胖症的影响；(A)身体形态的表型变化(左：Control；中：Model；右：C.minuta)；(B)体重变化；标注不同小写字母表示组间差异性显著(p<0.05)，标注相同小写字母表示组间差异性不显著(p>0.05)；Figure 1 shows the effect of Christensenella minuta intervention on obesity; (A) phenotypic changes in body shape (left: Control; middle: Model; right: C.minuta); (B) body weight Change; different lowercase letters indicate significant differences between groups (p<0.05), and the same lowercase letters indicate no significant differences between groups (p>0.05);
图2为小克里斯滕森氏菌(Christensenella minuta)干预对血糖的影响；(A)0-12周血糖指数的动态变化；(B)第12周血糖。标注不同小写字母表示组间差异性显著(p<0.05)，标注相同小写字母表示组间差异性不显著(p>0.05)；Figure 2 shows the effect of Christensenella minuta intervention on blood sugar; (A) dynamic changes of blood sugar index in 0-12 weeks; (B) blood sugar in week 12. Labeling with different lowercase letters indicates significant difference between groups (p<0.05), and marking with the same lowercase letter indicates no significant difference between groups (p>0.05);
图3为小克里斯滕森氏菌(Christensenella minuta)干预对机体葡萄糖代谢的影响；(A)葡萄糖耐受实验的血糖动态变化；(B)血糖曲线的曲线下血糖。标注不同小写字母表示组间差异性显著(p<0.05)，标注相同小写字母表示组间差异性不显著(p>0.05)；Figure 3 is the effect of Christensenella minuta intervention on glucose metabolism in the body; (A) dynamic changes in blood glucose in glucose tolerance test; (B) blood glucose under the curve of blood glucose curve. Labeling with different lowercase letters indicates significant difference between groups (p<0.05), and marking with the same lowercase letter indicates no significant difference between groups (p>0.05);
图4为小克里斯滕森氏菌(Christensenella minuta)干预对机体血清中生化指标的影响；(A)总胆固醇(Total Cholesterol,CHO)；(B)甘油三酯(Total Triglyceride，TG)；(C)血清尿酸(Uric acid,UA)；标注不同小写字母表示组间差异性显著(p<0.05)，标注相同小写字母表示组间差异性不显著(p>0.05)。Figure 4 is the effect of Christensenella minuta (Christensenella minuta) intervention on biochemical indicators in body serum; (A) total cholesterol (Total Cholesterol, CHO); (B) triglyceride (Total Triglyceride, TG); ( C) Serum uric acid (Uric acid, UA); different lowercase letters indicate significant differences between groups (p<0.05), and the same lowercase letters indicate no significant differences between groups (p>0.05).
具体实施方式Detailed ways
本发明公开了一种小克里斯滕森氏菌在制备治疗和/或预防高尿酸相关疾病的药物中的应用。本领域技术人员可以借鉴本文内容，适当改进工艺参数实现。特别需要指出的是，所有类似的替换和改动对本领域技术人员来说是显而易见的，它们都被视为包括在本发明。本发明的方法及应用已经通过较佳实施例进行了描述，相关人员明显能在不脱离本发明内容、精神和范围内对本文的方法和应用进行改动或适当变更与组合，来实现和应用本发明技术。The invention discloses an application of Christensenella minor in the preparation of medicines for treating and/or preventing diseases related to high uric acid. Those skilled in the art can refer to the content of this article to appropriately improve the process parameters to achieve. In particular, it should be pointed out that all similar replacements and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously make changes or appropriate changes and combinations to the method and application herein without departing from the content, spirit and scope of the present invention to realize and apply the present invention Invent technology.
以下结合实施例对本发明进行进一步阐述：The present invention is further elaborated below in conjunction with embodiment:
实施例1：小克里斯滕森氏菌干预试验Example 1: Intervention Test of Christensenella minor
1.实验材料：小克里斯滕森氏菌(Christensenella minuta,DSM22607)来自德国微生物菌种保藏中心(DSMZ)。1. Experimental materials: Christensenella minuta (DSM22607) was obtained from the German Culture Collection of Microorganisms (DSMZ).
2.实验试剂：血糖仪、血糖试纸，普和希健康医疗器械(上海)有限公司。2. Experimental reagents: blood glucose meter, blood glucose test strips, Puhexi Health Medical Devices (Shanghai) Co., Ltd.
3.实验动物：C57BL/6JNifdc雄性小鼠，购自浙江维通利华实验动物技术有限公司(合格证编号：20210728Abzz0619000723)。在环境为光照时间昼夜12h交替，温度为20～25℃，相对湿度为50±5％的暨南大学实验动物中心适应性饲养，自由摄食。实验操作均按照《暨南大学实验动物伦理委员会》相关 要求进行。3. Experimental animals: C57BL/6JNifdc male mice, purchased from Zhejiang Weitong Lihua Experimental Animal Technology Co., Ltd. (certificate number: 20210728Abzz0619000723). The animals were reared adaptively in the Experimental Animal Center of Jinan University with a light time of 12 hours alternating between day and night, a temperature of 20-25°C, and a relative humidity of 50±5%, and free feeding. All experimental operations were carried out in accordance with the relevant requirements of the "Jinan University Experimental Animal Ethics Committee".
4.实验方法4. Experimental method
(1)实验动物分组及模型建立(1) Experimental animal grouping and model establishment
利用体重分层法对C57BL/6JNifdc雄性小鼠随机分成4组，分别为Control组，Model组，C.minuta组和二甲双胍组。建立高糖高脂饮食模型，用纯水配置果糖水溶液给予Model组、C.minuta组和二甲双胍组动物自由饮用，同时给予Model组、C.minuta组和二甲双胍组动物高脂肪饲料自由摄取造模至实验结束。C57BL/6JNifdc male mice were randomly divided into 4 groups by weight stratification method, namely Control group, Model group, C.minuta group and metformin group. A high-sugar and high-fat diet model was established, and fructose aqueous solution was prepared with pure water and given to the animals in the Model group, C. The experiment is over.
(2)干预处理(2) Intervention treatment
C.minuta组和二甲双胍组小鼠在造模四周后开始进行干预，且干预至实验结束。其中，Control组和Model组均灌胃相应体积的水，而C.minuta组均灌胃相应体积的小克里斯滕森氏菌(Christensenella minuta)干预物，二甲双胍组均灌胃相应体积的二甲双胍干预物。The mice in the C.minuta group and the metformin group began to be intervened four weeks after the establishment of the model, and the intervention lasted until the end of the experiment. Among them, the Control group and the Model group were given the corresponding volume of water, while the C. things.
(3)体重(3) weight
Control组，Model组和C.minuta组小鼠均在造模第0天、第四周、第八周、第十二周在电子天平上称重。同时，对小鼠进行身体形态进行拍照记录，以及计算肥胖度对小鼠进行肥胖症评估。The mice in the Control group, the Model group and the C.minuta group were all weighed on the electronic balance at the 0th day, the fourth week, the eighth week, and the twelfth week of modeling. At the same time, the body shape of the mice was photographed and recorded, and the degree of obesity was calculated to evaluate the obesity of the mice.
肥胖度＝(实际体重-标准体重)÷标准体重×±100％Obesity = (actual weight - standard weight) ÷ standard weight × ± 100%
肥胖度在±10％之内，判断为正常适中；肥胖度超过10％，判断为超重；肥胖度超过20％-30％，判断为轻度肥胖；肥胖度超过30％-50％，判断为中度肥胖；肥胖度超过50％，以上，判断为重度肥胖；肥胖度小于-10％，判断为偏瘦；肥胖度小于-20％以上，判断为消瘦。If the obesity degree is within ±10%, it is judged as normal and moderate; if the obesity degree exceeds 10%, it is judged as overweight; if the obesity degree exceeds 20%-30%, it is judged as mildly obese; if the obesity degree exceeds 30%-50%, it is judged as Moderately obese; obesity over 50% and above, judged as severe obesity; obesity below -10%, judged as underweight; obesity below -20% above, judged as emaciated.
(4)血糖分析(4) Blood sugar analysis
禁食6小时后，对Control组，Model组和C.minuta组小鼠进行尾静脉取血，采用血糖仪和血糖试纸对血样进行血糖测试并记录分析。After fasting for 6 hours, the mice in the Control group, the Model group and the C.minuta group were taken blood from the tail vein, and the blood glucose was tested with a blood glucose meter and blood glucose test paper and recorded and analyzed.
(5)OGTT分析(5) OGTT analysis
禁食6小时不禁水一段时间后，对Control组，Model组和C.minuta组小鼠腹腔注射剂量为2g/kg的葡萄糖溶液，葡萄糖浓度为400mg/mL，体重为20g的小鼠注射量为0.1mL。注射葡萄糖后0分钟，30分钟，60分钟，120分钟 采用尾静脉取血的方式测定小鼠的血糖值。After fasting for 6 hours without water for a period of time, the mice in the Control group, the Model group and the C.minuta group were intraperitoneally injected with a dose of 2g/kg of glucose solution. 0.1mL. Blood glucose levels of the mice were measured by taking blood from the tail vein at 0 minutes, 30 minutes, 60 minutes, and 120 minutes after the glucose injection.
(6)CHO\TG\UA分析(6) CHO\TG\UA analysis
禁食不禁水6h后，对所有组别小鼠采用眼眶取血的方式取血，血液常温静置30min后，于4℃在3000rpm/min条件下离心15min，取上层血清，分装后置于-80℃保存待用。随后，通过Thermo Fisher公司的全自动多功能动物生化分析仪(Indiko Plus)对血清生化指标CHO、TG、UA进行测试并记录分析。After fasting and drinking for 6 hours, blood was collected from mice in all groups by taking blood from the eye sockets. After the blood was allowed to stand at room temperature for 30 minutes, it was centrifuged at 3000 rpm/min at 4°C for 15 minutes. Store at -80°C until use. Subsequently, the serum biochemical indicators CHO, TG, and UA were tested and recorded and analyzed by the automatic multifunctional animal biochemical analyzer (Indiko Plus) of Thermo Fisher Company.
5.实验结果5. Experimental results
本发明成功构建了高糖高脂饮食模型，高糖高脂饮食造模后，与Control组相比，Model组小鼠体型肥大，体重出现了显著上升，如图1所示，图1为小克里斯滕森氏菌(Christensenella minuta)干预对肥胖症的影响，通过计算肥胖度，小鼠可确诊为肥胖症。与此同时，Model组小鼠也出现血糖指数异常，如图2和表1所示，其中图2为小克里斯滕森氏菌(Christensenella minuta)干预对血糖的影响，表1为小鼠血糖及AUC血糖指标；进一步进行血糖耐受分析，发现Model组小鼠出现葡萄糖代谢异常，可诊断为糖尿病，如图3所示，图3为小克里斯滕森氏菌(Christensenella minuta)干预对机体葡萄糖代谢的影响。The present invention has successfully constructed a high-sugar and high-fat diet model. After the high-sugar and high-fat diet model was established, compared with the Control group, the Model group mice were hypertrophied and their body weight increased significantly, as shown in Figure 1. The effect of Christensenella minuta intervention on obesity, which can be diagnosed in mice by calculating the degree of obesity. At the same time, the mice in the Model group also had abnormal blood sugar index, as shown in Figure 2 and Table 1. Figure 2 shows the effect of Christensenella minuta intervention on blood sugar, and Table 1 shows the blood sugar levels of the mice. and AUC blood sugar index; further analysis of blood sugar tolerance found that the mice in the Model group had abnormal glucose metabolism, which could be diagnosed as diabetes, as shown in Figure 3. Figure 3 shows the effect of Christensenella minuta intervention on the body Effects on glucose metabolism.
表1：小鼠血糖及AUC血糖指标Table 1: Mouse blood glucose and AUC blood glucose indicators
Figure PCTCN2022132718-appb-000001
Figure PCTCN2022132718-appb-000001
结合生化指标检查分析，发现Model组和二甲双胍组小鼠血清中总胆固醇(CHO)、总甘油三酯(TG)和血清尿酸(UA)均显著升高，如图4和表2所示，图4是小克里斯滕森氏菌(Christensenella minuta)干预对机体血清中生化指标的影响，表2是小鼠生化指标；总胆固醇指数是判断高胆固醇血症的重要指标，总甘油三酯是动脉硬化的关键危险因子，血清尿酸常见于痛风，基于高糖高脂饮食习惯，结合其他指标可诊断Model组和二甲双胍组小鼠具有高胆固醇血症伴随动脉粥样硬化的症状以及痛风高发风险。而小克里斯滕森氏菌 (Christensenella minuta)干预可显著有效的减少体重、降低血糖值、降低血清总甘油三酯、降低血清尿酸以及改善葡萄糖代谢异常等现象。二甲双胍作为公认的治疗糖尿病的药物，结果显示C.minuta组小鼠中血清总甘油三酯和血清尿酸的降低效果均显著优于二甲双胍组。Combined with the analysis of biochemical indicators, it was found that the total cholesterol (CHO), total triglyceride (TG) and serum uric acid (UA) in the serum of the Model group and the metformin group were significantly increased, as shown in Figure 4 and Table 2. 4 is the impact of small Christensenella (Christensenella minuta) intervention on the biochemical indicators in the body serum, table 2 is the biochemical indicators of mice; the total cholesterol index is an important indicator for judging hypercholesterolemia, and the total triglyceride is the arterial The key risk factor for sclerosis, serum uric acid, is common in gout. Based on the high-sugar and high-fat diet, combined with other indicators, it can be diagnosed that the mice in the Model group and the metformin group have symptoms of hypercholesterolemia accompanied by atherosclerosis and a high risk of gout. The intervention of Christensenella minuta can significantly and effectively reduce body weight, blood sugar, serum total triglycerides, serum uric acid, and abnormal glucose metabolism. Metformin is recognized as a drug for the treatment of diabetes. The results showed that the reduction effect of serum total triglyceride and serum uric acid in the mice of C.minuta group was significantly better than that of metformin group.
表2：小鼠生化指标Table 2: Biochemical indicators of mice
Figure PCTCN2022132718-appb-000002
Figure PCTCN2022132718-appb-000002
本发明指出了小克里斯滕森氏菌(Christensenella minuta)在治疗和/或预防日常高糖高脂饮食诱发的肥胖症、代谢综合征和痛风的作用，发现小克里斯滕森氏菌(Christensenella minuta)可以作为改善肥胖、降低高血糖、降低高胆固醇血症病发风险、降低动脉粥样硬化发生和降低痛风风险的有效功能成分。The present invention points out the role of Christensenella minuta in the treatment and/or prevention of obesity, metabolic syndrome and gout induced by daily high-sugar and high-fat diet, and finds that Christensenella minuta (Christensenella minuta) minuta) can be used as an effective functional ingredient to improve obesity, reduce hyperglycemia, reduce the risk of hypercholesterolemia, reduce the occurrence of atherosclerosis and reduce the risk of gout.
本发明内容仅仅举例说明了要求保护的一些具体实施方案，其中一个或更多个技术方案中所记载的技术特征可以与任意的一个或多个技术方案相组合，这些经组合而得到的技术方案也在本申请保护范围内，就像这些经组合而得到的技术方案已经在本发明公开内容中具体记载一样。The summary of the present invention only exemplifies some specific embodiments of the claims, wherein the technical features recorded in one or more technical solutions can be combined with any one or more technical solutions, and the technical solutions obtained by these combinations It is also within the scope of protection of the present application, just as these combined technical solutions have been specifically recorded in the disclosure content of the present invention.

Claims (7)

  1. 一种小克里斯滕森氏菌(Christensenella minuta)在制备治疗和/或预防高尿酸相关疾病的药物中的应用。An application of Christensenella minuta in the preparation of medicines for treating and/or preventing diseases related to high uric acid.
  2. 根据权利要求1所述的应用，其特征在于，所述小克里斯滕森氏菌为小克里斯滕森氏菌DSM22607。The application according to claim 1, wherein said Christensenella minor is Christensenella minor DSM22607.
  3. 根据权利要求1所述的应用，其特征在于，所述的高尿酸相关疾病为高尿酸血症或痛风疾病。The use according to claim 1, characterized in that the hyperuricemia-related disease is hyperuricemia or gout.
  4. 根据权利要求1所述的应用，其特征在于，所述药物为小克里斯滕森氏菌以及药学上可接受的载体。The application according to claim 1, characterized in that the drug is Christensenella minor and a pharmaceutically acceptable carrier.
  5. 根据权利要求4所述的应用，其特征在于，所述药物的剂型为口服制剂或注射制剂。The application according to claim 4, characterized in that, the dosage form of the medicine is an oral preparation or an injection preparation.
  6. 根据权利要求5所述的应用，其特征在于，所述口服制剂为片剂、胶囊、颗粒、浓缩丸或液剂。The application according to claim 5, characterized in that, the oral preparation is tablet, capsule, granule, concentrated pill or liquid.
  7. 根据权利要求5所述的应用，其特征在于，所述注射制剂为液体注射剂、注射用粉剂或注射用片剂。The application according to claim 5, characterized in that, the injection preparation is a liquid injection, a powder for injection or a tablet for injection.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020182916A1 (en) * 2019-03-11 2020-09-17 Lnc Therapeutics Bacterium of the christensenellaceae family for the prevention and/or treatment of chronic inflammatory diseases and/or inflammatory gastrointestinal diseases and/or cancers
WO2021013944A1 (en) * 2019-07-24 2021-01-28 Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement Faecalibacterium prausnitzii and christensenella bacterial strains for the treatment and prevention of bowel inflammation
CN113069475A (en) * 2021-04-06 2021-07-06 慕恩（广州）生物科技有限公司 Bacterial strain, composition and application
CN113166714A (en) * 2018-11-28 2021-07-23 最高科研理事会 Klitensiscoleceae bacteria comprising Klitensiella minutissima and uses thereof
CN113230387A (en) * 2021-04-06 2021-08-10 慕恩（广州）生物科技有限公司 Combined medicine containing microorganism and blood sugar and blood fat reducing medicine
CN114259507A (en) * 2021-12-27 2022-04-01 暨南大学 Application of Klebsiella minutissima in preparing medicine for treating and/or preventing hyperuricemia-related diseases

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101103994B (en) * 2006-07-13 2010-08-18 中国科学院地理科学与资源研究所 Medicine for preventing and treating gout and hyperuricemia
US10806759B2 (en) * 2016-09-06 2020-10-20 Bgi Shenzhen Christensenella intestinihominis and application thereof
CN110656130B (en) * 2019-11-15 2021-05-11 滨州医学院 Astragalus membranaceus-paecilomyces cicadae fermentation mycoplasm, preparation method and application

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113166714A (en) * 2018-11-28 2021-07-23 最高科研理事会 Klitensiscoleceae bacteria comprising Klitensiella minutissima and uses thereof
WO2020182916A1 (en) * 2019-03-11 2020-09-17 Lnc Therapeutics Bacterium of the christensenellaceae family for the prevention and/or treatment of chronic inflammatory diseases and/or inflammatory gastrointestinal diseases and/or cancers
WO2021013944A1 (en) * 2019-07-24 2021-01-28 Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement Faecalibacterium prausnitzii and christensenella bacterial strains for the treatment and prevention of bowel inflammation
CN113069475A (en) * 2021-04-06 2021-07-06 慕恩（广州）生物科技有限公司 Bacterial strain, composition and application
CN113230387A (en) * 2021-04-06 2021-08-10 慕恩（广州）生物科技有限公司 Combined medicine containing microorganism and blood sugar and blood fat reducing medicine
CN114259507A (en) * 2021-12-27 2022-04-01 暨南大学 Application of Klebsiella minutissima in preparing medicine for treating and/or preventing hyperuricemia-related diseases

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
"Master's Thesis", 11 November 2020, SOUTH CHINA UNIVERSITY OF TECHNOLOGY, CN, article YANG, HAIHUA: "Potential Probiotic Function of Christensenella Minuta on Host Intestinal Health", pages: 1 - 109, XP009546888, DOI: 10.27151/d.cnki.ghnlu.2020.004991 *
MAZIER WILFRID, LE CORF KATY, MARTINEZ CCORI, TUDELA HéLOïSE, KISSI DéBORAH, KROPP CAMILLE, COUBARD CHRISLAIN, SOTO: "A New Strain of Christensenella minuta as a Potential Biotherapy for Obesity and Associated Metabolic Diseases", CELLS, vol. 10, no. 4, pages 823, XP055802117, DOI: 10.3390/cells10040823 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116919994A (en) * 2023-09-15 2023-10-24 中国农业大学 Application of Klebsiella minutissima Teng Senshi bacteria in preparation of products for treating polycystic ovary syndrome
CN116919994B (en) * 2023-09-15 2023-12-08 中国农业大学 Application of Klebsiella minutissima Teng Senshi bacteria in preparation of medicine for treating polycystic ovary syndrome

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