CN114392351A - 毛螺菌科细菌与注射用人免疫球蛋白的联合用药物 - Google Patents
毛螺菌科细菌与注射用人免疫球蛋白的联合用药物 Download PDFInfo
- Publication number
- CN114392351A CN114392351A CN202110791991.XA CN202110791991A CN114392351A CN 114392351 A CN114392351 A CN 114392351A CN 202110791991 A CN202110791991 A CN 202110791991A CN 114392351 A CN114392351 A CN 114392351A
- Authority
- CN
- China
- Prior art keywords
- combination
- human immunoglobulin
- injection
- lachnospiraceae
- drug
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 241001112693 Lachnospiraceae Species 0.000 title claims abstract description 45
- 108060003951 Immunoglobulin Proteins 0.000 title claims abstract description 37
- 102000018358 immunoglobulin Human genes 0.000 title claims abstract description 37
- 239000003814 drug Substances 0.000 title claims abstract description 36
- 238000002347 injection Methods 0.000 title claims abstract description 21
- 239000007924 injection Substances 0.000 title claims abstract description 21
- 238000001959 radiotherapy Methods 0.000 claims abstract description 19
- 230000006378 damage Effects 0.000 claims abstract description 13
- 241000894006 Bacteria Species 0.000 claims abstract description 12
- 230000002285 radioactive effect Effects 0.000 claims abstract description 10
- 229940079593 drug Drugs 0.000 claims description 16
- 206010003694 Atrophy Diseases 0.000 claims description 13
- 206010061218 Inflammation Diseases 0.000 claims description 13
- 230000037444 atrophy Effects 0.000 claims description 13
- 230000004054 inflammatory process Effects 0.000 claims description 13
- 210000000952 spleen Anatomy 0.000 claims description 12
- 210000001541 thymus gland Anatomy 0.000 claims description 12
- 208000019155 Radiation injury Diseases 0.000 claims description 10
- 230000003394 haemopoietic effect Effects 0.000 claims description 9
- 229940000425 combination drug Drugs 0.000 claims description 8
- 230000005855 radiation Effects 0.000 claims description 8
- 201000002364 leukopenia Diseases 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 231100001022 leukopenia Toxicity 0.000 claims description 6
- 241000234615 Musaceae Species 0.000 claims description 4
- 238000010255 intramuscular injection Methods 0.000 claims description 4
- 239000007927 intramuscular injection Substances 0.000 claims description 4
- 238000010253 intravenous injection Methods 0.000 claims description 4
- 238000010254 subcutaneous injection Methods 0.000 claims description 4
- 239000007929 subcutaneous injection Substances 0.000 claims description 4
- 241001465754 Metazoa Species 0.000 claims description 3
- 230000000259 anti-tumor effect Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 6
- 210000000813 small intestine Anatomy 0.000 description 11
- 108090001005 Interleukin-6 Proteins 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- 210000002429 large intestine Anatomy 0.000 description 6
- 208000004232 Enteritis Diseases 0.000 description 5
- 102100040247 Tumor necrosis factor Human genes 0.000 description 5
- 230000003187 abdominal effect Effects 0.000 description 5
- 230000037396 body weight Effects 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 description 4
- 230000003442 weekly effect Effects 0.000 description 4
- 241000904817 Lachnospiraceae bacterium Species 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000000890 drug combination Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 208000003243 intestinal obstruction Diseases 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 239000000941 radioactive substance Substances 0.000 description 2
- 238000004904 shortening Methods 0.000 description 2
- 208000006678 Abdominal Neoplasms Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 229920002488 Hemicellulose Polymers 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000011200 Kawasaki disease Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100288498 Mus musculus Large1 gene Proteins 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 206010061336 Pelvic neoplasm Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 208000031951 Primary immunodeficiency Diseases 0.000 description 1
- 206010054979 Secondary immunodeficiency Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 238000012271 agricultural production Methods 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 208000021735 chronic enteritis Diseases 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 210000002490 intestinal epithelial cell Anatomy 0.000 description 1
- 208000037817 intestinal injury Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 description 1
- 238000005025 nuclear technology Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000021391 short chain fatty acids Nutrition 0.000 description 1
- 150000004666 short chain fatty acids Chemical class 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000003582 thrombocytopenic effect Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- 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
- A61K35/741—Probiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- 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
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/16—Blood plasma; Blood serum
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cell Biology (AREA)
- Toxicology (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Developmental Biology & Embryology (AREA)
- Virology (AREA)
- Zoology (AREA)
- Endocrinology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
本发明公开了毛螺菌科细菌与注射用人免疫球蛋白的联合用药物,属于生物制药领域。研究表明,注射用人免疫球蛋白具有治疗放射性损伤的作用,而毛螺菌科细菌和注射用人免疫球蛋白联用能进一步增强该治疗作用。因此,本发明的联合用药物对接受放疗的病患以及意外接受过多辐照者具有重要意义。
Description
技术领域
本发明属于生物制药领域。
背景技术
癌症是人类第二大死因,放射治疗(“放疗”)是一种被广泛应用的癌症治疗手段,对于癌症治疗的贡献率高达18%,仅次于手术治疗而明显高于化学治疗和生物治疗。但不可回避的是,放射治疗伴随着不同程度的以炎症为代表的急性和以纤维化为代表慢性器官损伤。具体而言,头颈部肿瘤的放射治疗往往导致口腔粘膜炎;胸部肿瘤放射治疗往往导致慢性肺炎;盆腹部肿瘤放射治疗往往导致腹泻、慢性肠炎、肠梗阻等。而以白细胞下降、髓系偏移为代表的造血损伤和以肠炎和肠梗阻为代表的消化道损伤在多部位的放射治疗均十分常见,并将导致放射治疗提前终止,严重的降低了患者的生活质量甚至造成患者死亡。增加放射治疗的剂量也将不可避免的增加健康器官发生急慢性放射性损伤的风险。因此,降低放射治疗伴随的急慢性放射性损伤,将更大限度的促进放射治疗的临床应用,提高肿瘤患者预后的生活质量。
核技术、核工业的迅猛发展,使核能在工农业生产、科学技术研究和国防民生中的应用日益广泛。“核”的和平使用已成为全球各国不能回避的发展动力。核设施或核活动中发生偏离运行工况的状态即核事故的发生,将对放射性工作人员以及周边民众产生意外的、非自愿的照射,导致放射性损伤。因此,在核设施附近应常备治疗放射性损伤的药物。
注射用人免疫球蛋白是由多人份健康人血浆混合后,经分离纯化、病毒灭活/去除等步骤制成的免疫球蛋白产品,主要活性成分是针对各种外源性抗原和自身抗原的多克隆免疫球蛋白组合。注射用人免疫球蛋白的给药方式可分为:静注人免疫球蛋白(intravenous immunoglobulin,IVIg)、肌注人免疫球蛋白(intramuscularimmunoglobulin,IMIg)和皮下注射人免疫球蛋白(subcutaneousimmunoglobulin,SCIg)。注射用人免疫球蛋白是治疗原发性免疫缺乏症、继发性免疫缺陷病、自身免疫性疾病(川崎病、特发性血小板减少性紫瘫)的有效药物,临床使用广泛。
发明人通过研究发现,注射用人免疫球蛋白在放射性损伤中有一定的救治作用,具体体现在:辐照导致小鼠胸腺、脾脏萎缩,淋巴细胞数量减少,大肠缩短,小肠炎症水平升高,并导致死亡。而注射用人免疫球蛋白则有助于小鼠逆转前述症状,并能减少死亡。但注射用人免疫球蛋白仅在雌性中的效果显著,而在雄性中效果还有待提高(专利申请202010925913.X)。
毛螺菌科(Lachnospiraceae)细菌是一类可定植于肠道的细菌,其被报道具有消化植物源的纤维素和半纤维素的能力,以增加食物的生物利用率;它还能生产短链脂肪酸,以作为肠道上皮细胞的主要营养供给。Hao Guo等报道,使用23株Lachnospiraceae的混合物可用于治疗放射性损伤,但这23株Lachnospiraceae之间的比例不清,制备复杂,且随着Lachnospiraceae丰度降低,其治疗效果下降(Guo H等.Multi-omics analyses ofradiation survivors identify radioprotective microbes andmetabolites.Science.2020 Oct 30;370(6516):eaay9097.)。
发明内容
本发明要解决的问题是:提供一种增强注射用人免疫球蛋白在治疗放射性损伤中疗效的联合用药物。
本发明中,“放射性损伤”指放射治疗的X射线、加速器、以及放射性物质发出的α射线、β射线和/或γ射线对身体照射后产生的损伤,所述照射既包括对身体表面的照射,也包括放射性物质进入体内后对体内细胞的照射。本发明中,ATCC为美国模式培养物集存库(American type culture collection)的简写。
本发明的技术方案如下:
一种治疗放射性损伤的联合用药物,所述联合用药物含有相同或者不同规格的同时或者分别给药的毛螺菌科细菌和注射用人免疫球蛋白;
所述注射用人免疫球蛋白为:静注人免疫球蛋白、肌注人免疫球蛋白和/或皮下注射人免疫球蛋白
进一步的,所述毛螺菌科细菌为ATCC编号为BAA-2278的Lachnospiraceaebacterium。
进一步的,所述联合用药物是恢复放射性损伤后身体造血功能的药物。
进一步的,所述联合用药物是缓解放射性损伤导致的胸腺萎缩、脾脏萎缩、白细胞减少和/或炎症的药物。进一步的,所述炎症为肠炎。
进一步的,所述联合用药物是男性用药物或雄性动物用药物。
本发明还提供了前述联合用药物在制备降低放射性损伤的药物中的用途。
一种治疗肿瘤的联合用药物,所述联合用药物含有相同或者不同规格的同时或者分别给药的抗肿瘤放疗药物、毛螺菌科细菌和注射用人免疫球蛋白;
所述注射用人免疫球蛋白为:静注人免疫球蛋白、肌注人免疫球蛋白和/或皮下注射人免疫球蛋白
进一步的,所述毛螺菌科细菌为ATCC编号为BAA-2278的Lachnospiraceaebacterium。
进一步的,所述联合用药物是恢复放疗后身体造血功能的药物。
进一步的,所述联合用药物是缓解放疗导致的胸腺萎缩、脾脏萎缩、白细胞减少和/或炎症的药物。进一步的,所述炎症为肠炎。
进一步的,所述联合用药物是男性用药物或雄性动物用药物。
本发明的有益效果如下:
1)本发明的联合用药物可用于恢复辐照后的身体造血功能;
2)本发明的联合用药物可缓解辐照导致的胸腺萎缩、脾脏萎缩、白细胞减少和/或炎症;
3)本发明的联合用药物克服了单独使用IVIg无法显效治疗雄性动物放射性损伤的缺点。
显然,根据本发明的上述内容,按照本领域的普通技术知识和惯用手段,在不脱离本发明上述基本技术思想前提下,还可以做出其它多种形式的修改、替换或变更。
以下通过实施例形式的具体实施方式,对本发明的上述内容再作进一步的详细说明。但不应将此理解为本发明上述主题的范围仅限于以下的实例。凡基于本发明上述内容所实现的技术均属于本发明的范围。
附图说明
图1:胸腺外观。
图2:脾脏外观。
图3:外周血白细胞计数。
图4:TAI组和Lachnospiraceae组大肠外观。
图5:TAI组和Lachnospiraceae组小肠内TNF-α和IL-6的水平。纵坐标的mL表示提取小肠中TNF-α和IL-6所用PBS的体积,单位重量的小肠所用PBS体积一致。
图6:IVIg组和IVIg+Lachnospiraceae组大肠外观。
图7:IVIg组和IVIg+Lachnospiraceae组小肠内TNF-α和IL-6的水平。纵坐标的mL表示提取小肠中TNF-α和IL-6所用PBS的体积,单位重量的小肠所用PBS体积一致。
具体实施方式
实施例1 IVIg与Lachnospiraceae联用治疗放射性损伤
本实施例中使用的Lachnospiraceae为Lachnospiraceae bacterium(ATCC BAA-2278)。
1.方法
1.1、5Gy全身辐照分析造血损伤
雄性小鼠24只,分成2组:
①IVIg组,12只;
②IVIg+Lachnospiraceae组12只;
IVIg组在全身辐照后5min静脉注射IVIg一次,随后每周注射IVIg两次,持续两周,每次剂量为0.3g/Kg体重。
IVIg+Lachnospiraceae组在全身辐照前30min内口服Lachnospiraceae一次,辐照后5min内静脉注射IVIg一次,随后每周注射IVIg两次,持续两周,并且每两天口服Lachnospiraceae一次。每次Lachnospiraceae剂量为1*107个;每次IVIg剂量为0.3g/Kg体重。
1.2、12Gy腹部局部辐照分析肠道损伤。
雄性小鼠44只,分成4组:
①TAI组,10只;
②Lachnospiraceae组,10只;
③IVIg组,12只;
④IVIg+Lachnospiraceae组12只;
TAI组只进行腹部局部辐照,然后注射与其他组药物等体积的PBS。
Lachnospiraceae组在腹部局部照射前30min内口服Lachnospiraceae一次,以后每两天口服Lachnospiraceae一次,每次Lachnospiraceae剂量为1*107个。
IVIg组在腹部局部辐照后5min静脉注射IVIg一次,随后每周注射IVIg两次,持续两周,每次剂量为0.3g/Kg体重。
IVIg+Lachnospiraceae组在腹部局部辐照前30min内口服Lachnospiraceae一次,辐照后5min内静脉注射IVIg一次,随后每周注射IVIg两次,持续两周,并且每两天口服Lachnospiraceae一次。每次Lachnospiraceae剂量为1*107个;每次IVIg剂量为0.3g/Kg体重。
然后,对小鼠采集外周血,检测白细胞数量,并取脾脏、胸腺、小肠进行观察,进一步检测小肠内IL-6、TNF-α水平。
2.结果
全身辐照会导致小鼠胸腺、脾脏萎缩,降低造血功能,白细胞随之减少。如图1~3所示,IVIg+Lachnospiraceae组相比IVIg组的胸腺和脾脏体积显著增加,白细胞数量显著增加。表明IVIg与Lachnospiraceae联用相比单独使用IVIg可进一步恢复小鼠的胸腺、脾脏大小,进而恢复被辐照小鼠的造血功能。
腹部局部辐照会导致小鼠大肠变短,且小肠内炎性因子TNFα和IL-6会升高,发生肠炎(Li,et al.Gut commensal derived-valeric acid protects against radiationinjuries.Gut Microbes,2020,11:789-806.)。只口服Lachnospiraceae不注射IVIg(Lachnospiraceae组),大肠长度以及小肠中炎性因子TNFα和IL-6相比TAI组无差异(图4和图5),表明只口服Lachnospiraceae不能抑制辐照引起的炎症。如图6所示,IVIg+Lachnospiraceae组的大肠的长度比IVIg组更长;IVIg+Lachnospiraceae组小肠中炎性因子TNFα和IL-6相比IVIg组水平降低(图7)。表明IVIg与Lachnospiraceae联用相比单独使用IVIg可进一步抑制辐照导致的炎症。
本实施例的结果表明,单独使用Lachnospiraceae无法抑制辐照引起的炎症,而IVIg与Lachnospiraceae联用相比单独使用IVIg可进一步抑制辐照导致的炎症。
综上,本发明的联合用药物可用于恢复辐照后的身体造血功能,并能缓解辐照导致的胸腺萎缩、脾脏萎缩、白细胞减少和/或炎症;且该联合用药物克服了单独使用IVIg无法显效治疗雄性动物的缺点。
Claims (10)
1.一种治疗放射性损伤的联合用药物,其特征在于:所述联合用药物含有相同或者不同规格的同时或者分别给药的毛螺菌科细菌和注射用人免疫球蛋白;
所述注射用人免疫球蛋白为:静注人免疫球蛋白、肌注人免疫球蛋白和/或皮下注射人免疫球蛋白。
2.如权利要求1所述的联合用药物,其特征在于:所述毛螺菌科细菌为ATCC编号为BAA-2278的Lachnospiraceae bacterium。
3.如权利要求1所述的联合用药物,其特征在于:所述联合用药物是恢复放射性损伤后身体造血功能的药物。
4.如权利要求1所述的联合用药物,其特征在于:所述联合用药物是缓解放射性损伤导致的胸腺萎缩、脾脏萎缩、白细胞减少和/或炎症的药物。
5.如权利要求1所述的联合用药物,其特征在于:所述联合用药物是男性用药物或雄性动物用药物。
6.权利要求1~5所述的联合用药物在制备降低放射性损伤的药物中的用途。
7.一种治疗肿瘤的联合用药物,其特征在于:所述联合用药物含有相同或者不同规格的同时或者分别给药的抗肿瘤放疗药物、毛螺菌科细菌和注射用人免疫球蛋白;
所述注射用人免疫球蛋白为:静注人免疫球蛋白、肌注人免疫球蛋白和/或皮下注射人免疫球蛋白。
8.如权利要求7所述的联合用药物,其特征在于:所述毛螺菌科细菌为ATCC编号为BAA-2278的Lachnospiraceae bacterium。
9.如权利要求7所述的联合用药物,其特征在于:所述联合用药物是恢复放疗后身体造血功能的药物。
10.如权利要求7所述的联合用药物,其特征在于:所述联合用药物是缓解放疗导致的胸腺萎缩、脾脏萎缩、白细胞减少和/或炎症的药物;优选所述联合用药物是男性用药物或雄性动物用药物。
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110791991.XA CN114392351B (zh) | 2021-07-13 | 2021-07-13 | 毛螺菌科细菌与注射用人免疫球蛋白的联合用药物 |
US17/861,811 US20220347233A1 (en) | 2021-07-13 | 2022-07-11 | Combination Drugs of Lachnospiraceae Bacteria and Human Immunoglobulin |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110791991.XA CN114392351B (zh) | 2021-07-13 | 2021-07-13 | 毛螺菌科细菌与注射用人免疫球蛋白的联合用药物 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114392351A true CN114392351A (zh) | 2022-04-26 |
CN114392351B CN114392351B (zh) | 2024-04-05 |
Family
ID=81225281
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202110791991.XA Active CN114392351B (zh) | 2021-07-13 | 2021-07-13 | 毛螺菌科细菌与注射用人免疫球蛋白的联合用药物 |
Country Status (2)
Country | Link |
---|---|
US (1) | US20220347233A1 (zh) |
CN (1) | CN114392351B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114392351B (zh) * | 2021-07-13 | 2024-04-05 | 中国医学科学院放射医学研究所 | 毛螺菌科细菌与注射用人免疫球蛋白的联合用药物 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5562902A (en) * | 1994-03-14 | 1996-10-08 | Arp Biomed, Inc. | Immunotherapeutic method of treating cancerous diseases by administration of intravenous immunoglobulin |
US20130177574A1 (en) * | 2012-01-11 | 2013-07-11 | Paul I. Terasaki Foundation Laboratory | ANTI-HLA CLASS-Ib ANTIBODIES MIMIC IMMUNOREACTIVITY AND IMMUNOMODULATORY FUNCTIONS OF INTRAVENOUS IMMUNOGLOBULIN (IVIg) USEFUL AS THERAPEUTIC IVIg MIMETICS AND METHODS OF THEIR USE |
WO2020124088A1 (en) * | 2018-12-14 | 2020-06-18 | The University Of North Carolina At Chapel Hill | Lachnospiraceae mitigates against radiation-induced hematopoietic/gastrointestinal injury and death, and promotes cancer control by radiation |
US20220347233A1 (en) * | 2021-07-13 | 2022-11-03 | Institute Of Radiation Medicine, Chinese Academy Of Medical Sciences | Combination Drugs of Lachnospiraceae Bacteria and Human Immunoglobulin |
-
2021
- 2021-07-13 CN CN202110791991.XA patent/CN114392351B/zh active Active
-
2022
- 2022-07-11 US US17/861,811 patent/US20220347233A1/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5562902A (en) * | 1994-03-14 | 1996-10-08 | Arp Biomed, Inc. | Immunotherapeutic method of treating cancerous diseases by administration of intravenous immunoglobulin |
US20130177574A1 (en) * | 2012-01-11 | 2013-07-11 | Paul I. Terasaki Foundation Laboratory | ANTI-HLA CLASS-Ib ANTIBODIES MIMIC IMMUNOREACTIVITY AND IMMUNOMODULATORY FUNCTIONS OF INTRAVENOUS IMMUNOGLOBULIN (IVIg) USEFUL AS THERAPEUTIC IVIg MIMETICS AND METHODS OF THEIR USE |
WO2020124088A1 (en) * | 2018-12-14 | 2020-06-18 | The University Of North Carolina At Chapel Hill | Lachnospiraceae mitigates against radiation-induced hematopoietic/gastrointestinal injury and death, and promotes cancer control by radiation |
US20220347233A1 (en) * | 2021-07-13 | 2022-11-03 | Institute Of Radiation Medicine, Chinese Academy Of Medical Sciences | Combination Drugs of Lachnospiraceae Bacteria and Human Immunoglobulin |
Non-Patent Citations (2)
Title |
---|
WANG, Z. 等: "Sexual dimorphism in gut microbiota dictates therapeutic efficacy of intravenous immunoglobulin on radiotherapy complications", JOURNAL OF ADVANCED RESEARCH, vol. 46, pages 123 - 133 * |
孙琪云 等: "静脉注射免疫球蛋白在急性放射病人救治中的应用", 解放军医学杂志, vol. 32, no. 4, pages 408 * |
Also Published As
Publication number | Publication date |
---|---|
US20220347233A1 (en) | 2022-11-03 |
CN114392351B (zh) | 2024-04-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1566178B1 (en) | Remedy for fibromyalgia | |
CN107669692A (zh) | Mpla在制备电离辐射致肠道损伤防治药物中的应用 | |
CN110960539A (zh) | 桑皮苷a及其衍生物在制备保护肠道屏障的药物中的应用 | |
Sagami et al. | Successful use of adalimumab for treating pyoderma gangrenosum with ulcerative colitis under corticosteroid-tapering conditions | |
CN101380346B (zh) | 一种治疗肿瘤的中药组合物及其制作方法 | |
CN114392351B (zh) | 毛螺菌科细菌与注射用人免疫球蛋白的联合用药物 | |
CN101049323A (zh) | 一种用于治疗慢性退行性疾病的保健药及其生产方法 | |
CN1686506A (zh) | 一种治疗乳腺增生疾病的药物和制备方法及其应用 | |
Douer et al. | Methimazole‐induced agranulocytosis: Growth inhibition of myeloid progenitor cells by the patient's serum | |
CN117045687A (zh) | 一种凝结芽孢杆菌在制备防治电离辐射致肠道损伤的药物中的应用 | |
CN102166183B (zh) | 免疫刺激剂口服糖浆及其制作方法 | |
CN114377124B (zh) | 次黄嘌呤与注射用人免疫球蛋白的联合用药物 | |
CN102309743A (zh) | 重组人血小板生成素的新用途 | |
CN105456185A (zh) | 一种复方黄芪多糖注射液及其制备方法 | |
CN114129722B (zh) | 注射用人免疫球蛋白在制备预防或治疗辐照损伤的药物中的用途 | |
CN1723956A (zh) | 一种治疗慢性胃炎、胃癌的药物及其制备方法 | |
CN1468602A (zh) | 柚皮苷在制备支持性治疗非典型性肺炎药物中的应用 | |
CN111358833A (zh) | 夏枯草提取物及其在制备治疗甲状腺疾病药物中的应用 | |
CN115708840B (zh) | 神香草提取物在制备抗肺癌药物中的应用 | |
CN101966245B (zh) | 一种治疗畜禽病毒性疾病的复方注射液及其制备方法 | |
CN1100550C (zh) | 一种适用于各种癌症的中药组合物 | |
CN114903933B (zh) | 一种治疗羊附红细胞体病的中药及其制备方法和应用 | |
CN105816862A (zh) | 乌司他丁在制备治疗前列腺癌药物中的用途 | |
CN110772559A (zh) | 一种具有化瘤功效的中药组合物 | |
CN105688048B (zh) | 一种治疗类风湿关节炎的中药制剂 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |