CN117205266A - A pharmaceutical composition for reducing the harm of ionizing radiation - Google Patents
A pharmaceutical composition for reducing the harm of ionizing radiation Download PDFInfo
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- CN117205266A CN117205266A CN202311415105.9A CN202311415105A CN117205266A CN 117205266 A CN117205266 A CN 117205266A CN 202311415105 A CN202311415105 A CN 202311415105A CN 117205266 A CN117205266 A CN 117205266A
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- pharmaceutical composition
- ionizing radiation
- rehmannia glutinosa
- polysaccharide
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Abstract
本发明涉及一种减轻电离辐射危害的药物组合物,属于中药技术领域。由以下重量份成分组成:熟地黄570‑630份、水晶兰苷4‑14份、耐斯糖17‑27份、麦冬多糖60‑80份、茯苓多糖75‑95份、茯苓酸1‑5份、五味子素1‑3份。本发明的药物组合物的优点是,可以促进受电离辐射伤害小鼠外周血白细胞数升高,降低骨髓细胞微核数,有助于机体修复因电离辐射造成的损伤,具有减轻电离辐射危害的功效。The invention relates to a pharmaceutical composition for reducing the harm of ionizing radiation, and belongs to the technical field of traditional Chinese medicine. It is composed of the following ingredients by weight: 570-630 parts of Rehmannia glutinosa, 4-14 parts of Crystal Cyanoside, 17-27 parts of Nicetose, 60-80 parts of Ophiopogon japonicus polysaccharide, 75-95 parts of Poria polysaccharide, and 1-5 parts of Poria acid. 1-3 parts of Schisandrin. The pharmaceutical composition of the present invention has the advantage that it can promote the increase in the number of peripheral blood leukocytes of mice injured by ionizing radiation, reduce the number of micronuclei in bone marrow cells, help the body repair the damage caused by ionizing radiation, and has the effect of reducing the harm of ionizing radiation. effect.
Description
技术领域Technical field
本发明属于中药技术领域,具体涉及一种减轻电离辐射危害的药物组合物。The invention belongs to the technical field of traditional Chinese medicine, and specifically relates to a pharmaceutical composition for reducing the harm of ionizing radiation.
背景技术Background technique
电离辐射,是指携带足以使物质原子或分子发生电离现象的能量的辐射,包括宇宙射线、X射线和来自放射性物质的辐射。电离辐射主要有两大来源:一种是自然辐射,来自宇宙和地球表面的空气和水以及人体的放射性物质;另一种是人工辐射,包括医学领域光放射学,医学成像与放射疗法。由于受到电离辐射而引起的机体全身或局部组织损害称为电离辐射性损伤。电离辐射性损伤的主要来源是恶性肿瘤的放射治疗,当放射线杀死肿瘤细胞的同时,也会对周围的正常组织造成一定的伤害,引起机体的多个系统发生放射性损伤,其中最常见的是造血系统和免疫系统损伤,以骨髓抑制为主,贫血及出血危险显著增加,免疫功能下降,致使并发症增多,严重影响病人的生活质量。Ionizing radiation refers to radiation that carries enough energy to ionize atoms or molecules of matter, including cosmic rays, X-rays and radiation from radioactive materials. There are two main sources of ionizing radiation: one is natural radiation, which comes from the air and water on the universe and the earth's surface, as well as radioactive substances in the human body; the other is artificial radiation, including photoradiology, medical imaging and radiotherapy in the medical field. Damage to the body's entire body or local tissues caused by exposure to ionizing radiation is called ionizing radiation injury. The main source of ionizing radiation damage is radiotherapy for malignant tumors. When radiation kills tumor cells, it will also cause certain damage to surrounding normal tissues, causing radiation damage to multiple systems of the body. The most common of these is Damage to the hematopoietic system and immune system, mainly bone marrow suppression, significantly increases the risk of anemia and bleeding, and decreases immune function, leading to an increase in complications and seriously affecting the patient's quality of life.
目前针对电离辐射损伤,西医治疗多采用大剂量抗生素及糖皮质激素,以及化学合成物质半胱胺、氨磷丁和雌二醇等,疗效不甚理想,且毒副作用大,不能长期使用。近年来许多学者研究发现中医药可提高放疗患者的生活质量、延长生存期并对放疗引起的损伤有良好防护作用。多种中药配伍可调理放疗所致的脾胃亏虚,有效防止骨髓抑制。据报道,中药十全大补汤(药方组成:当归、川芎、白芍、熟地黄、人参、白术、茯苓、炙甘草、黄芪、肉桂)、八珍汤(药方组成:人参、白术、白茯苓、当归、川芎、白芍、熟地黄、甘草炙)、养正合剂(药方组成:红参、黄芪、枸杞子、女贞子、猪苓、茯苓)、补中益气汤(药方组成:黄芪、炙甘草、人参、当归、橘皮、升麻、柴胡、白术)、当归补血汤(药方组成:黄芪、当归)、六味地黄丸(药方组成:熟地黄、酒萸肉、牡丹皮、山药、茯苓、泽泻)等对辐射所致的血液、遗传、免疫、抗氧化系统等损伤均有较好的改善和防治作用。一些中药中的成分如多糖、生物碱、皂苷、挥发油、香豆素类等可发挥自由基清除、促粒细胞造血、白细胞升高、增强机体免疫力及修复造血组织损伤等作用。Currently, for ionizing radiation damage, Western medicine mostly uses high-dose antibiotics and glucocorticoids, as well as chemically synthesized substances such as cysteamine, amifostine, and estradiol. The efficacy is not ideal, and the side effects are high, so it cannot be used for a long time. In recent years, many scholars have found that traditional Chinese medicine can improve the quality of life of radiotherapy patients, prolong survival, and have a good protective effect on damage caused by radiotherapy. The combination of various traditional Chinese medicines can regulate spleen and stomach deficiency caused by radiotherapy and effectively prevent bone marrow suppression. According to reports, the traditional Chinese medicine Shiquan Dabu Decoction (composition of Chinese medicine: Angelica sinensis, Chuanxiong rhizome, white peony root, Rehmannia glutinosa, ginseng, Atractylodes macrocephala, Poria cocos, licorice root, astragalus, cinnamon), Bazhen decoction (composition of Chinese medicine: ginseng, Atractylodes macrocephala, white Poria cocos) , Angelica sinensis, Ligusticum chuanxiong, white peony root, Rehmannia glutinosa, licorice root), Yangzheng mixture (prescription composition: red ginseng, astragalus, wolfberry, Ligustrum lucidum, Polyporus, Poria), Buzhong Yiqi decoction (prescription composition: astragalus , Zhigancao, ginseng, angelica, orange peel, cohosh, bupleurum, and atractylodes), Danggui Buxue Decoction (prescription: astragalus, angelica), Liuwei Dihuang Pills (prescription: Rehmannia glutinosa, cornus, peony bark, yam) , Poria cocos, Alisma), etc., have a good effect on improving and preventing damage to the blood, genetics, immunity, antioxidant system and other damage caused by radiation. Some ingredients in traditional Chinese medicine, such as polysaccharides, alkaloids, saponins, volatile oils, coumarins, etc., can play a role in scavenging free radicals, promoting granulocyte hematopoiesis, increasing white blood cells, enhancing the body's immunity, and repairing damage to hematopoietic tissue.
从中医病因学角度来看,电离辐射会穿过皮毛、口鼻、官窍侵入人体,损伤脏腑,引起脏腑功能紊乱、气血阴阳失调,所诱发的病理演变过程与毒邪致病特征相吻合,因此可以看作一种外来之毒邪。同时,电离辐射能量高、热源性和穿透力都很强,在发挥作用时释放大量能量,使毒邪兼具火热之气,根据其作用特点可以看成一种火毒、热毒之邪。以火、瘀、虚为基本病机,主要病因为机体“津血亏虚,邪热内生,阴虚则火旺,燥热难耐”。引火汤方出于清代陈士铎的《辨证录》,其药物组成为:熟地黄,巴戟天,茯苓,麦冬,北五味。引火汤通过滋阴以降虚火,引火归元以协调阴阳,适用于阴液亏虚而内生阳热的阴虚火旺之象。申请人前期探讨了引火汤防治电离辐射损伤的作用机制[周立慧,等.基于网络药理学探讨引火汤防治放射性损伤的作用机制[J].特产研究,2022,44(4):44-52.]。From the perspective of traditional Chinese medicine etiology, ionizing radiation will invade the human body through the fur, mouth, nose, and orifices, damage the organs, cause organ dysfunction, and imbalance of qi, blood, yin and yang. The pathological evolution process induced is consistent with the pathogenic characteristics of toxins. , so it can be regarded as an external poisonous evil. At the same time, ionizing radiation has high energy, strong heat source and penetrating power. It releases a large amount of energy when it works, making the poisonous evil both fiery and hot. According to its action characteristics, it can be regarded as a fire poison and a heat poisonous evil. Fire, blood stasis, and deficiency are the basic pathogenesis. The main cause is "deficiency of fluid and blood, endogenous pathogenic heat, and deficiency of yin results in strong fire and unbearable dryness and heat." The recipe for Yinhuo Decoction comes from Chen Shiduo's "Syndrome Dialectical Record" of the Qing Dynasty. Its medicinal composition is: Rehmannia glutinosa, Morinda officinalis, Poria, Ophiopogon japonicus, and Northern Five Flavors. Yinhuo Decoction nourishes yin to reduce deficient fire, and yinhuo returns to its origin to coordinate yin and yang. It is suitable for cases of yin deficiency and excessive fire when yin fluid is deficient and yang heat is generated internally. The applicant initially discussed the mechanism of action of Yinhuo Tang in preventing and treating ionizing radiation damage [Zhou Lihui, et al. Based on network pharmacology to explore the mechanism of action of Yinhuo Tang in preventing and treating radioactive damage [J]. Specialty Products Research, 2022, 44(4): 44-52. ].
发明内容Contents of the invention
本发明提供一种减轻电离辐射危害的药物组合物,目的在于提供一种成分明确,效果更佳的减轻电离辐射性损伤的药物组合物及其药物。本发明通过对引火汤方的深入研究,寻找其相关有效成分,开发一种成分明确,效果更佳的可减轻电离辐射性损伤的药物组合物。应用该药物组合物及其药物,有效帮助机体修复由于受到电离辐射导致的机体损伤,促进机体尽快恢复;可用于减少电离辐射伤害,减少癌症放疗的副作用。The present invention provides a pharmaceutical composition for reducing the harm of ionizing radiation. The purpose is to provide a pharmaceutical composition and medicine for reducing the damage caused by ionizing radiation with clear ingredients and better effects. The present invention conducts in-depth research on the Huohuo Decoction, searches for its relevant active ingredients, and develops a pharmaceutical composition with clear ingredients and better effects that can reduce ionizing radiation damage. The use of the pharmaceutical composition and its medicines can effectively help the body repair damage caused by ionizing radiation and promote the body's recovery as soon as possible; it can be used to reduce ionizing radiation damage and reduce the side effects of cancer radiotherapy.
本发明采用的技术方案是:由以下重量份成分组成:The technical solution adopted by the present invention is: it consists of the following components by weight:
熟地黄570-630份、水晶兰苷4-14份、耐斯糖17-27份、麦冬多糖60-80份、茯苓多糖75-95份、茯苓酸1-5份、五味子素1-3份。570-630 parts of Rehmannia glutinosa, 4-14 parts of Crystal Cyanoside, 17-27 parts of Nessin, 60-80 parts of Ophiopogon japonicus polysaccharide, 75-95 parts of Poria polysaccharide, 1-5 parts of Poria acid, and 1-3 parts of Schizandrin share.
所述麦冬多糖的制备方法为:麦冬粉碎得到粒径为120-180目的麦冬粉,加水浸泡:麦冬粉与水的质量体积比为1:8-16,g/mL,浸泡时间为0.5-2h,煎煮提取,所述煎煮的温度为90-100℃,煎煮2-4次,每次煎煮时间为0.5-2h,分离滤液,浓缩、干燥得到麦冬多糖。The preparation method of the Ophiopogon japonicus polysaccharide is: crush Ophiopogon japonicus to obtain Ophiopogon japonicus powder with a particle size of 120-180 mesh, add water to soak: the mass volume ratio of Ophiopogon japonicus powder to water is 1:8-16, g/mL, soaking time 0.5-2h, decoct and extract, the decoction temperature is 90-100°C, decoct 2-4 times, each decoction time is 0.5-2h, separate the filtrate, concentrate and dry to obtain Ophiopogon japonicus polysaccharide.
所述干燥为常规干燥中:冷冻干燥、真空干燥、喷雾干燥、沸腾干燥或微波干燥中的任一种。The drying is any one of conventional drying: freeze drying, vacuum drying, spray drying, boiling drying or microwave drying.
一种减轻电离辐射危害的药物组合物的制备方法,包括下列步骤:A preparation method of a pharmaceutical composition for reducing the hazards of ionizing radiation, including the following steps:
(1)将熟地黄粉碎得到熟地黄粉,加水浸泡,煎煮提取,分离滤液,浓缩、干燥得到熟地黄提取物;(1) Crush Rehmannia glutinosa to obtain Rehmannia glutinosa powder, add water to soak, decoct and extract, separate the filtrate, concentrate and dry to obtain Rehmannia glutinosa extract;
(2)将熟地黄提取物与剩余组合物组分水晶兰苷、耐斯糖、麦冬多糖、茯苓多糖、茯苓酸、五味子素混合,得到药物组合物。(2) Mix the Rehmannia glutinosa extract with the remaining composition components crystalline glycoside, Nessose, Ophiopogon japonicus polysaccharide, Poria polysaccharide, Poria acid, and Schisandrin to obtain a pharmaceutical composition.
所述步骤(1)中熟地黄粉的粒径为过5-20目筛,与水的料液质量体积比比为1:8-20,g/mL;熟地黄粉与水混合后,浸泡0.5-2h,煎煮提取2-4次,每次1-2h,提取液过滤,合并滤液,将滤液浓缩、干燥得到熟地黄提取物。In the step (1), the particle size of the cooked rehmannia glutinosa powder is passed through a 5-20 mesh sieve, and the material-to-liquid mass volume ratio with water is 1:8-20, g/mL; after the cooked rehmannia glutinosa powder is mixed with water, soak for 0.5-2h , decoct and extract 2-4 times, 1-2 hours each time, filter the extract, combine the filtrate, concentrate and dry the filtrate to obtain the Rehmannia glutinosa extract.
一种减轻电离辐射危害的药物组合物在制备减轻电离辐射危害的药物中的应用。Application of a pharmaceutical composition for reducing the harm of ionizing radiation in preparing medicine for reducing the harm of ionizing radiation.
一种减轻电离辐射危害的药物组合物包括所述的药物组合物和医学上可接受的辅料;所述药物的剂型为任何可药用的剂型中丸剂、片剂、胶囊剂、颗粒剂、合剂或口服液中的任一种。A pharmaceutical composition for reducing the harm of ionizing radiation includes the pharmaceutical composition and medically acceptable excipients; the dosage form of the pharmaceutical is any pharmaceutically acceptable dosage form: pills, tablets, capsules, granules, mixtures or any of the oral solutions.
所述医学上可接受的辅料,包括淀粉、糊精、蔗糖、乳粉、甜味剂、甘露糖醇、乳糖、纤维素类及其衍生物、碳酸钙、环糊精、β-环糊精、磷脂类材料、硬脂酸镁、滑石粉、防腐剂或香精。The medically acceptable excipients include starch, dextrin, sucrose, milk powder, sweeteners, mannitol, lactose, cellulose and its derivatives, calcium carbonate, cyclodextrin, β-cyclodextrin , phospholipid materials, magnesium stearate, talc, preservatives or flavors.
本发明的有益效果是:The beneficial effects of the present invention are:
1、本发明在引火汤方的基础上,对组方的中药成分和活性成分进行筛选,得到了本发明的含有熟地黄、水晶兰苷、耐斯糖、麦冬多糖、茯苓多糖、茯苓酸、五味子素的组合物,各活性成分相互协同配合,可以帮助机体修复由于受到电离辐射引起损伤,促进受损造血系统和免疫系统恢复,升高外周血白细胞数和降低骨髓细胞微核数。本药物组合物及其制剂能有效预防和减轻电离辐射危害,有利于减少癌症放疗的副作用。1. On the basis of the recipe of Yinhuo Decoction, the present invention screened the traditional Chinese medicine ingredients and active ingredients of the prescription, and obtained the present invention containing Rehmannia glutinosa, Crystal Cyanoside, Naisose, Ophiopogon japonicus polysaccharide, Poria polysaccharide, and Poria acid. , Schisandrin composition, each active ingredient cooperates with each other to help the body repair damage caused by ionizing radiation, promote the recovery of the damaged hematopoietic system and immune system, increase the number of peripheral blood white blood cells and reduce the number of bone marrow cell micronuclei. The pharmaceutical composition and its preparations can effectively prevent and reduce the harm of ionizing radiation, and are beneficial to reducing the side effects of cancer radiotherapy.
2、本发明选用各味药材中的主要活性成分,合理配伍,协同发挥作用,能高效修复因电离辐射引起的机体损伤;通过优选提取方法制备组合物的原料,活性成分提取率高,充分利用药材资源;采用特定方法制备药物组合物,组合物成分明确,可以保证质量稳定可控,疗效稳定,有利于推广应用,可用于接受放疗的肿瘤患者减少副作用,以及减轻各种来源的电离辐射伤害。2. The present invention selects the main active ingredients from various medicinal materials, combines them reasonably, and works synergistically to effectively repair body damage caused by ionizing radiation; the raw materials of the composition are prepared by optimizing the extraction method, and the extraction rate of active ingredients is high, making full use of them. Medicinal material resources; using specific methods to prepare pharmaceutical compositions, the composition has clear ingredients, which can ensure stable and controllable quality and stable efficacy, which is conducive to popularization and application. It can be used to reduce side effects for tumor patients undergoing radiotherapy and reduce ionizing radiation damage from various sources. .
具体实施方式Detailed ways
为了进一步阐明本发明的特征,下面结合具体实施例进一步阐述。需要说明的是下述实施例仅为本发明的优选实施例,并非全部。基于下述实施例,本领域技术人员可以根据所公开的内容对本发明做出多种改变和修饰,而其也应当属于本发明要求保护的范围之中。下述实施例中,若无特殊说明,所用的操作方法均为常规操作方法,所用设备均为常规设备,各个实施例所用设备材料均相同,制备方法为常规混匀。下述实施例中,所用原料均为市售产品,所用水均为纯水。In order to further clarify the features of the present invention, the following is further described in conjunction with specific embodiments. It should be noted that the following embodiments are only preferred embodiments of the present invention, not all of them. Based on the following examples, those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, which should also fall within the scope of protection claimed by the present invention. In the following examples, unless otherwise specified, the operating methods used are conventional operating methods, the equipment used are conventional equipment, the equipment materials used in each embodiment are the same, and the preparation method is conventional mixing. In the following examples, all raw materials used are commercially available products, and all water used is pure water.
以下非限制性实施例可以使本领域的普通技术人员更全面的理解本发明,但不以任何方式限制本发明。下述内容仅仅是对本发明要求保护的范围的示例性说明,本领域技术人员可以根据所公开的内容对本发明做出多种改变和修饰,而其也应当属于本发明要求保护的范围之中。The following non-limiting examples can enable those of ordinary skill in the art to understand the present invention more comprehensively, but do not limit the present invention in any way. The following content is only an illustrative description of the scope of protection claimed by the present invention. Those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, which should also fall within the scope of protection claimed by the present invention.
当实施例给出数值范围时,应理解,除非本发明另有说明,每个数值范围的两个端点以及两个端点之间任何一个数值均可选用。除非另外定义,本文中使用的所有技术和科学术语具有与本发明所属技术领域的普通技术人员通常理解的相同意义。When the examples give numerical ranges, it should be understood that, unless otherwise stated in the present invention, both endpoints of each numerical range and any value between the two endpoints can be selected. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
下面以具体实施例的方式对本发明作进一步的说明,本发明实施例中所使用的各种化学试剂如无特殊说明均通过常规商业途径获得。下述实施例和对比例中,所述水晶兰苷(分子式C16H22O11,CAS No:5945-50-6)、耐斯糖(分子式C24H42O21,CAS No:13133-07-8)、茯苓多糖(CAS No:65673-98-1)、茯苓酸(分子式C33H52O5,CAS No:29070-92-6)、五味子素(分子式C24H32O7,CAS No:7432-28-2),所述熟地黄是玄参科植物地黄干燥块根,按照《中国药典》规定的炮制方法炮制的加工品,具体的炮制方法对技术效果无影响,如无特殊说明,实施例和对比例中采用的熟地黄为市售产品。所述麦冬为百合科植物麦冬的干燥块根,麦冬养阴生津,润肺清心,用于肺燥干咳,阴虚痨嗽,喉痹咽痛,津伤口渴,内热消渴,心烦失眠,肠燥便秘。The present invention will be further described below in the form of specific examples. Unless otherwise specified, various chemical reagents used in the examples of the present invention are obtained through conventional commercial channels. In the following examples and comparative examples, the crystalline cyanoside (molecular formula C 16 H 22 O 11 , CAS No: 5945-50-6), nesose (molecular formula C 24 H 42 O 21 , CAS No: 13133- 07-8), Poria polysaccharide (CAS No: 65673-98-1), Poria acid (Molecular formula C 33 H 52 O 5 , CAS No: 29070-92-6), Schisandrin (Molecular formula C 24 H 32 O 7 , CAS No: 7432-28-2), the Rehmannia glutinosa is the dried root tuber of Scrophulariaceae plant Rehmannia glutinosa, processed products according to the processing method stipulated in the "Chinese Pharmacopoeia". The specific processing method has no impact on the technical effect. If there is no special Note that the Rehmannia glutinosa used in the examples and comparative examples is a commercially available product. Described Ophiopogon japonicus is the dried root tuber of Liliaceae plant Ophiopogon japonicus. Ophiopogon japonicus nourishes yin and promotes fluid production, moistens the lungs and clears the heart. It is used for dry cough due to yin deficiency, tuberculosis cough caused by yin deficiency, sore throat, sore throat, thirst in body fluids, wounds, internal heat, quenching thirst, and upset. Insomnia, intestinal dryness and constipation.
下述实施例中,所述麦冬多糖的制备方法为:麦冬粉碎,过120目筛,得到麦冬粉,与15倍量的水混合,浸泡1h,95-100℃煎煮,煎煮3次,每次煎煮1h进行活性物质的提取,分离滤液,浓缩、干燥得到麦冬多糖。In the following examples, the preparation method of the Ophiopogon japonicus polysaccharide is: crush Ophiopogon japonicus, pass through a 120-mesh sieve to obtain Ophiopogon japonicus powder, mix with 15 times the amount of water, soak for 1 hour, decoct at 95-100°C, and decoct Decoction three times for 1 hour each time to extract active substances, separate the filtrate, concentrate and dry to obtain Ophiopogon japonicus polysaccharide.
实施例1-5Examples 1-5
一种减轻电离辐射危害的药物组合物,按照重量份计包括组分如表1所示:A pharmaceutical composition for reducing the hazards of ionizing radiation, including components as shown in Table 1 in parts by weight:
表1实施例1-5中各组分及其重量份Table 1 Components and their weight parts in Examples 1-5
实施例1-5的药物组合物的制备方法,包括步骤:The preparation method of the pharmaceutical composition of Examples 1-5 includes the steps:
(1)将熟地黄粉碎得到熟地黄粉,过20目筛,与水混合,熟地黄粉与水的体积比1:12,浸泡1h,煎煮提取3次,每次1.5h,提取液过滤,合并滤液,浓缩、干燥得到熟地黄提取物;(1) Crush Rehmannia glutinosa to obtain Rehmannia glutinosa powder, pass through a 20-mesh sieve, mix with water, the volume ratio of Rehmannia glutinosa powder to water is 1:12, soak for 1 hour, boil and extract 3 times, 1.5 hours each time, filter the extract and combine The filtrate is concentrated and dried to obtain Rehmannia glutinosa extract;
(2)将熟地黄提取物与剩余组合物组分水晶兰苷、耐斯糖、麦冬多糖、茯苓多糖、茯苓酸、五味子素混合,得到药物组合物。(2) Mix the Rehmannia glutinosa extract with the remaining composition components crystalline glycoside, Nessose, Ophiopogon japonicus polysaccharide, Poria polysaccharide, Poria acid, and Schisandrin to obtain a pharmaceutical composition.
对照提取物:根据引火汤原方组成(熟地三两,巴戟、麦冬一两,北味二钱,茯苓五钱)制备对照提取物,按照重量份包括以下成分:熟地黄600,巴戟200、麦冬200,北味40,茯苓100。将上述药材粉碎得到药材粉,过20目筛,与水混合,药材粉与水的体积比1:12,浸泡1h,煎煮提取3次,每次1.5h,提取液过滤,合并滤液,浓缩、干燥得到对照提取物。Control extract: Prepare the control extract according to the original recipe of Yinhuo Decoction (three liang of Rehmannia glutinosa, one liang of Morinda officinalis and Ophiopogon japonicus, two qian of Beiwei, and five qian of Poria cocos), and include the following ingredients in parts by weight: 600 parts of Rehmannia glutinosa, 200 parts of Morinda citrifolia, Ophiopogon japonicus 200, Beiwei 40, Poria 100. Crush the above medicinal materials to obtain medicinal powder, pass through a 20 mesh sieve, mix with water, the volume ratio of medicinal powder to water is 1:12, soak for 1 hour, decoct and extract 3 times, 1.5 hours each time, filter the extract, combine the filtrate, and concentrate , dried to obtain the control extract.
对比例1:所述的药物组合物按照重量份包括以下成分:熟地黄提取物600份、黄芪苷9份、耐斯糖22份、麦冬多糖70份、茯苓多糖85份、茯苓酸3份、五味子素2份。Comparative Example 1: The pharmaceutical composition includes the following ingredients in parts by weight: 600 parts of Rehmannia glutinosa extract, 9 parts of astragaloside, 22 parts of naiseose, 70 parts of Ophiopogon japonicus polysaccharide, 85 parts of Poria polysaccharide, and 3 parts of Poria acid. , 2 parts of Schisandrin.
上述药物组合物的制备方法同实施例1。The preparation method of the above pharmaceutical composition is the same as in Example 1.
与实施例1的区别在于,改变了药物组合物的组分,药物组合物中的水晶兰苷换成了黄芪苷,药物组合物的其余组分、重量份和制备方法均与实施例1相同。The difference from Example 1 is that the components of the pharmaceutical composition have been changed, and the crystalline cyanide in the pharmaceutical composition has been replaced by astragaloside. The remaining components, weight parts, and preparation methods of the pharmaceutical composition are the same as those in Example 1. .
对比例2:所述的药物组合物按照重量份包括以下成分:熟地黄提取物600份、水晶兰苷9份、蔗糖22份、果糖70份、茯苓聚糖85份、茯苓酸3份、五味子素2份。上述药物组合物的制备方法同实施例1。Comparative Example 2: The pharmaceutical composition includes the following ingredients in parts by weight: 600 parts of Rehmannia glutinosa extract, 9 parts of crystalline cyanide, 22 parts of sucrose, 70 parts of fructose, 85 parts of Poria polysaccharide, 3 parts of Poria acid, Schisandra chinensis 2 servings of vegetarian food. The preparation method of the above pharmaceutical composition is the same as in Example 1.
与实施例1的区别在于,改变了药物组合物的组分,药物组合物中的耐斯糖、麦冬多糖、茯苓多糖换成了蔗糖、果糖、茯苓聚糖。药物组合物的其余组分、重量份和制备方法均与实施例1相同。The difference from Example 1 is that the components of the pharmaceutical composition were changed, and the nesose, Ophiopogon japonicus polysaccharide and Poria polysaccharide in the pharmaceutical composition were replaced by sucrose, fructose and Poria polysaccharide. The remaining components, weight parts and preparation method of the pharmaceutical composition are the same as in Example 1.
对比例3:所述的药物组合物按照重量份包括以下成分:熟地黄提取物600份、水晶兰苷9份、耐斯糖22份、麦冬多糖70份、茯苓多糖85份、阿魏酸3份、五味子素2份。Comparative Example 3: The pharmaceutical composition includes the following ingredients in parts by weight: 600 parts of Rehmannia glutinosa extract, 9 parts of Crystal Cyanoside, 22 parts of Nessaccharide, 70 parts of Ophiopogon japonicus polysaccharide, 85 parts of Poria Polysaccharide, and ferulic acid 3 parts, 2 parts Schisandrin.
与实施例1的区别在于,改变了药物组合物的组分,药物组合物中的茯苓酸换成了阿魏酸。药物组合物的其余组分、重量份和制备方法均与实施例1相同。The difference from Example 1 is that the components of the pharmaceutical composition were changed, and the poria acid in the pharmaceutical composition was replaced by ferulic acid. The remaining components, weight parts and preparation method of the pharmaceutical composition are the same as in Example 1.
对比例4:所述的药物组合物按照重量份包括以下成分:熟地黄提取物600份、水晶兰苷9份、耐斯糖22份、麦冬多糖70份、茯苓多糖85份、茯苓酸3份、柠檬酸2份。Comparative Example 4: The pharmaceutical composition includes the following ingredients in parts by weight: 600 parts of Rehmannia glutinosa extract, 9 parts of crystalline cyanide, 22 parts of naisin, 70 parts of Ophiopogon japonicus polysaccharide, 85 parts of Poria polysaccharide, and 3 parts of Poria acid 2 parts of citric acid.
与实施例1的区别在于,改变了药物组合物的组分,药物组合物中的五味子素换成了柠檬酸。药物组合物的其余组分、重量份和制备方法均与实施例1相同。The difference from Example 1 is that the components of the pharmaceutical composition were changed, and the schisandrin in the pharmaceutical composition was replaced by citric acid. The remaining components, weight parts and preparation method of the pharmaceutical composition are the same as in Example 1.
功效评价试验Efficacy evaluation test
本发明开展药物组合物减轻电离辐射危害的功效评价试验,观察本发明的药物组合物对电离辐射损伤模型动物的影响,评价其减轻电离辐射伤害的效果。The present invention conducts an efficacy evaluation test of a pharmaceutical composition in reducing the harm of ionizing radiation, observes the effect of the pharmaceutical composition of the present invention on model animals damaged by ionizing radiation, and evaluates its effect in reducing the harm of ionizing radiation.
实验方法experimental method
实施例1-5和对比例1-4的药物组合物、对照提取物的制备方法:Preparation methods of pharmaceutical compositions and control extracts of Examples 1-5 and Comparative Examples 1-4:
1、按表1中实施例1-5及对比例1-4各组分的重量份,将实施例1-5及对比例1-4的组合物混匀,制成粉剂。按对照提取物的制备方法制备对照提取物,制成粉剂。临用时将粉剂以等量蒸馏水分散开,用时摇匀,4℃保存。评价实施例1-5、对比例1-4的组合物、以及对照提取物对电离辐射性损伤的保护作用。1. Mix the compositions of Examples 1-5 and Comparative Examples 1-4 according to the weight parts of each component of Examples 1-5 and Comparative Examples 1-4 in Table 1 to prepare a powder. Prepare the control extract according to the preparation method of the control extract and make it into powder. Before use, disperse the powder with an equal amount of distilled water, shake well before use, and store at 4°C. The compositions of Examples 1-5, Comparative Examples 1-4, and the control extract were evaluated for their protective effects against ionizing radiation damage.
2、实验动物:选用昆明健康SPF级雌性小鼠,体重18g~22g。2. Experimental animals: Kunming healthy SPF grade female mice, weighing 18g to 22g, were selected.
3、给药方式实施例1-5对比例1-4的药物组合物及对照提取物,按照剂量1.2g/kg给药。每日一次经口给予1次,连续灌胃28d后,进行辐照,之后继续给予受试物,到实验结束。小鼠灌胃体积为10mL/kgBW。同时设模型对照组(0mL/kgBW)均用无菌水代替受试物,每日灌胃体积与各受试物组相同。各组均给予维持饲料。3. Dosing Method: The pharmaceutical compositions and control extracts of Examples 1-5, Comparative Examples 1-4, are administered at a dose of 1.2g/kg. It was administered orally once a day, and after continuous gavage for 28 days, irradiation was performed, and then the test substance was continued to be administered until the end of the experiment. The intragastric volume of mice was 10 mL/kg BW. At the same time, the model control group (0mL/kgBW) used sterile water instead of the test substance, and the daily gavage volume was the same as that of each test substance group. Each group was given maintenance feed.
4.评价试验项目4. Evaluate pilot projects
4.1外周血白细胞计数实验:受试样品组于照射前后经口连续给予受试样品,剂量组与模型对照组均以同一剂量γ射线全身照射一次,照射剂量选择3.0Gy(吸收剂量率1.0Gy/60s,时间3min)。分别于照射前、照射后第3d、照射后第14d三次采末梢血20μL,加入0.38mL 1%盐酸中,混匀后,加入血球计数板中,计算计数池中四个大方格中白细胞总数。4.1 Peripheral blood leukocyte count experiment: The test sample group was continuously administered the test sample orally before and after irradiation. Both the dose group and the model control group were irradiated once with the same dose of γ-rays, and the irradiation dose was selected to be 3.0Gy (absorbed dose rate 1.0 Gy/60s, time 3min). Collect 20 μL of peripheral blood three times before irradiation, on the 3rd day after irradiation, and on the 14th day after irradiation. Add 0.38 mL of 1% hydrochloric acid. After mixing, add it to a hemocytometer counting board. Calculate the total number of white blood cells in the four large squares in the counting cell. .
4.2小鼠骨髓细胞微核实验:剂量组于照射前后经口连续给予受试样品,剂量组与辐射模型对照组均以同一剂量γ射线全身照射一次,照射剂量选择3.0Gy(吸收剂量率1.0Gy/60s,时间3min)。于照射后第3天,颈椎脱臼杀死动物,取胸骨,用止血钳挤出骨髓液与玻片一端的小牛血清混匀,常规涂片。涂片自然干燥后,放入甲醇中固定10min,放入Giemsa应用染液中,染色15min,立即用蒸馏水冲洗,晾干。镜检,每只动物计数1000个嗜多染红细胞中微核细胞数,微核率以千分率表示。4.2 Mouse bone marrow cell micronucleus experiment: The dose group was continuously orally administered test samples before and after irradiation. The dose group and the radiation model control group were all irradiated once with the same dose of γ-rays. The irradiation dose was selected to be 3.0Gy (absorbed dose rate 1.0 Gy/60s, time 3min). On the 3rd day after irradiation, the animals were killed by cervical dislocation, the sternum was removed, the bone marrow fluid was squeezed out with a hemostat and mixed with calf serum at one end of the slide, and a routine smear was performed. After the smear was naturally dried, it was fixed in methanol for 10 min, placed in Giemsa applied dye solution, stained for 15 min, rinsed immediately with distilled water, and dried. For microscopic examination, the number of micronucleated cells in 1,000 polychromatic erythrocytes per animal was counted, and the micronucleus rate was expressed in parts per thousand.
5.统计学分析5. Statistical analysis
应用统计软件SPSS29.0对各项指标的实验数据进行统计分析处理,数据结果用均数±标准差表示,组间比较采用单因素方差分析(ANOVA),两两比较采用LSD法,以p<0.05为差异有统计学意义。The statistical software SPSS29.0 was used to perform statistical analysis and processing on the experimental data of various indicators. The data results were expressed as mean ± standard deviation. Indicates that the one-way analysis of variance (ANOVA) was used for comparison between groups, and the LSD method was used for pairwise comparison. P<0.05 was considered as a statistically significant difference.
二、结果2. Results
1、外周血白细胞计数实验结果如表2所示:1. The experimental results of peripheral blood leukocyte count are shown in Table 2:
表2对X射线照射小鼠外周血白细胞数的影响(n=10,)Table 2 Effects on the number of peripheral blood leukocytes in mice irradiated with X-rays (n=10, )
注:与空白组相比,*:p<0.05,**:p<0.01;与模型组相比,#:p<0.05,##:p<0.01;与实例1相比,★:p<0.05,★★:p<0.01;与实例2相比,※:p<0.05,※※:p<0.01;与实例3相比,☆:p<0.05,☆☆:p<0.01;与实例4相比,◇:p<0.05,◇◇:p<0.01;与实例5相比,◆:p<0.05,◆◆:p<0.01Note: Compared with the blank group, * : p<0.05, ** : p<0.01; compared with the model group, # : p<0.05, ## : p<0.01; compared with Example 1, ★: p< 0.05, ★★: p<0.01; compared with Example 2, ※: p<0.05, ※※: p<0.01; compared with Example 3, ☆: p<0.05, ☆☆: p<0.01; compared with Example 4 Compared with, ◇: p<0.05, ◇◇: p<0.01; compared with Example 5, ◆: p<0.05, ◆◆: p<0.01
2.小鼠骨髓细胞微核实验结果如表3所示:2. The results of mouse bone marrow cell micronucleus experiment are shown in Table 3:
表3对X射线照射小鼠骨髓细胞微核率的影响(n=10,)Table 3 Effects on micronucleus rate of bone marrow cells in mice irradiated with X-rays (n=10, )
注:与空白组相比,*:p<0.05,**:p<0.01;与模型组相比,#:p<0.05,##:p<0.01;Note: Compared with the blank group, * : p<0.05, ** : p<0.01; compared with the model group, # : p<0.05, ## : p<0.01;
与实例1相比,★:p<0.05,★★:p<0.01;与实例2相比,※:p<0.05,※※:p<0.01;与实例3相比,☆:p<0.05,☆☆:p<0.01;与实例4相比,◇:p<0.05,◇◇:p<0.01;与实例5相比,◆:p<0.05,◆◆:p<0.01Compared with Example 1, ★: p<0.05, ★★: p<0.01; Compared with Example 2, ※: p<0.05, ※※: p<0.01; Compared with Example 3, ☆: p<0.05, ☆☆: p<0.01; compared with Example 4, ◇: p<0.05, ◇◇: p<0.01; compared with Example 5, ◆: p<0.05, ◆◆: p<0.01
三、结论3. Conclusion
对比例中1-4中依次将组合物中的成分替换为其他组分。由于黄芪对放疗引起的损伤有良好防护作用,故对比例1中采用黄芪中的主要活性成分黄芪苷替代巴戟天中的水晶兰苷。实验结果表明,对比例1效果不如实施例,与对照例效果相当。因为耐斯糖是蔗果四糖,麦冬多糖的单糖种类主要是果糖和葡萄糖,所以对比例2中采用果糖和蔗糖替换耐斯糖和麦冬多糖,用同样是茯苓中的成分茯苓聚糖替换茯苓多糖。实验结果表明,对比例2效果不如实施例,与对照例效果相当。当归具有补血作用,也是十全大补汤、八珍汤等用于放疗中成药的重要组成,阿魏酸是当归的指标成分,对比例3中采用阿魏酸替换茯苓酸。实验结果表明,对比例3效果不如实施例,与对照例效果相当。五味子中的活性化合物主要有两类成分,一类是木质素类化合物(五味子素等),另一类是有机酸(主要有柠檬酸、苹果酸等)。因此在对比例4中采用柠檬酸替代五味子素。实验结果表明,对比例4效果不如实施例,与对照例效果相当。总体来看,其中实施例效果优于根据引火汤方制备的对照提取物和对比例,对比例和对照提取物的效果相当。对比例1-4减轻受辐射小鼠机体伤害的效果均较实施例降低,说明本发明的药物组合物中各个成分都是最佳选择。In Comparative Examples 1-4, the components in the composition were replaced with other components in sequence. Since Astragalus has a good protective effect on damage caused by radiotherapy, in Comparative Example 1, astragaloside, the main active ingredient in Astragalus, was used to replace Crystal Cyanoside in Morinda officinalis. The experimental results show that the effect of Comparative Example 1 is not as good as that of the Example, but the effect is equivalent to that of the Comparative Example. Because naisitose is sucrose, and the monosaccharides of Ophiopogon japonicus polysaccharide are mainly fructose and glucose, so in Comparative Example 2, fructose and sucrose were used to replace naisitose and Ophiopogon japonicus polysaccharide, and Poria polysaccharide, which is also an ingredient in Poria cocos, was used. Sugar replaces Poria cocos polysaccharide. The experimental results show that the effect of Comparative Example 2 is not as good as that of the Example, but the effect is equivalent to that of the Comparative Example. Angelica sinensis has a blood-tonifying effect and is also an important component of traditional Chinese medicines such as Shiquan Dabu Decoction and Bazhen Decoction for radiotherapy. Ferulic acid is an index component of Angelica sinensis. In Comparative Example 3, ferulic acid was used to replace poria acid. The experimental results show that the effect of Comparative Example 3 is not as good as that of the Example, but the effect is equivalent to that of the Comparative Example. The active compounds in Schisandra chinensis mainly include two types of components, one is lignin compounds (schisandrin, etc.), and the other is organic acids (mainly citric acid, malic acid, etc.). Therefore, in Comparative Example 4, citric acid was used instead of schizandrin. The experimental results show that the effect of Comparative Example 4 is not as good as that of the Example, but is equivalent to the effect of the Comparative Example. Generally speaking, the effect of the embodiment is better than that of the control extract and the comparative example prepared according to the recipe of Yinhuo Decoction, and the effect of the comparative example and the control extract is equivalent. The effects of Comparative Examples 1-4 on reducing body damage in irradiated mice were all lower than those of the Examples, indicating that each component in the pharmaceutical composition of the present invention is the best choice.
本发明的药物组合物具有减轻电离辐射危害作用;可以有效促进血液系统恢复,增加受辐射小鼠外周血白细胞数,减少骨髓细胞微核数,减少机体染色体受损情况。本发明的药物组合物成分明确、配伍合理、疗效最佳。The pharmaceutical composition of the present invention has the effect of reducing the harm of ionizing radiation; it can effectively promote the recovery of the blood system, increase the number of peripheral blood leukocytes of irradiated mice, reduce the number of micronuclei of bone marrow cells, and reduce damage to the body's chromosomes. The pharmaceutical composition of the present invention has clear ingredients, reasonable compatibility and optimal curative effect.
最后应当说明的是,以上内容仅用以说明本发明的技术方案,而非对本发明保护范围的限制,本领域的普通技术人员对本发明的技术方案进行的简单修改或者等同替换,均不脱离本发明技术方案的实质和范围。Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, but does not limit the protection scope of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by those of ordinary skill in the art do not deviate from the scope of the present invention. The essence and scope of the technical solution of the invention.
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