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CN113559141B - Application of artemisia capillaris for preparing medicine for treating pulmonary fibrosis - Google Patents

Application of artemisia capillaris for preparing medicine for treating pulmonary fibrosis Download PDF

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CN113559141B
CN113559141B CN202110916478.9A CN202110916478A CN113559141B CN 113559141 B CN113559141 B CN 113559141B CN 202110916478 A CN202110916478 A CN 202110916478A CN 113559141 B CN113559141 B CN 113559141B
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魏成喜
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Abstract

The invention discloses application of artemisia capillaris for preparing a medicine for treating pulmonary fibrosis.

Description

茵陈蒿用于制备治疗肺纤维化药物的用途Use of Artemisia annua in preparing medicine for treating pulmonary fibrosis

技术领域technical field

本发明涉及茵陈蒿用于制备治疗肺纤维化药物的用途。The invention relates to the use of Artemisia annua for preparing medicine for treating pulmonary fibrosis.

背景技术Background technique

肺纤维化是一种原因不明的慢性炎症间质性肺疾病,如间质性肺炎、结缔组织引发的肺部疾病都会导致肺纤维化。近年来肺纤维化的发病率呈逐渐上升趋势,致死率高,对人类健康危害严重,正引起全世界的广泛关注。肺纤维化患者临床主要表现为进行性呼吸困难,最终发展为低氧血症和呼吸衰竭而死亡,确诊后平均存活时间为3年。肺纤维化发病原因复杂,机制不明,尚缺乏有效的治疗药物。目前临床上治疗肺纤维化以免疫抑制类和糖皮质激素类药物为主,但疗效不明显且毒副作用。Pulmonary fibrosis is a chronic inflammatory interstitial lung disease of unknown cause, such as interstitial pneumonia and lung diseases caused by connective tissue. In recent years, the incidence of pulmonary fibrosis is on the rise, with a high fatality rate and serious harm to human health. The main clinical manifestations of pulmonary fibrosis patients are progressive dyspnea, which eventually develops into hypoxemia and respiratory failure and death. The average survival time after diagnosis is 3 years. The pathogenesis of pulmonary fibrosis is complex, the mechanism is unknown, and there is still a lack of effective therapeutic drugs. At present, the clinical treatment of pulmonary fibrosis is mainly based on immunosuppressive drugs and glucocorticoid drugs, but the efficacy is not obvious and the side effects are not obvious.

茵陈蒿(学名:Artemisia capillaris Thunb.)是菊科,蒿属半灌木状草本植物,植株有浓烈的香气。茵陈蒿富含维生素及人体所需的多种微量元素和20余种氨基酸,具有很好的保健功能。茵陈蒿治病,最出名的就是茵陈蒿汤。在《伤寒论》中,茵陈蒿汤主要被用来治疗阳明病“瘀热在里”的“发黄”,而在《金匮要略方论》中,则被用来治疗黄疸病的“谷疸”。后世的医疗世家主要将茵陈蒿汤用来治疗湿热黄疸。而如今,茵陈蒿汤则更多的被用来治疗传染性肝炎,并在本方的基础上,时常增减药材,广泛运用于肝胆疾病的临床治疗。Artemisia capillaris Thunb. (scientific name: Artemisia capillaris Thunb.) is a semi-shrub-like herb of the family Compositae, and the plant has a strong aroma. Artemisia annua is rich in vitamins, various trace elements and more than 20 kinds of amino acids needed by the human body, and has good health care functions. The most famous one is Yinchenhao Decoction for treating diseases. In Treatise on Febrile Diseases, Yin Chenhao Decoction is mainly used to treat "yellowing" caused by "stagnation of heat in the interior" of Yangming disease, while in "Golden Chamber Yaolue Fang Lun", it is used to treat jaundice. "Gluten Jaundice". Later generations of medical families mainly used Yinchenhao Decoction to treat damp-heat jaundice. Today, Yinchenhao Decoction is more often used to treat infectious hepatitis, and on the basis of this recipe, the herbs are often added or removed, and it is widely used in the clinical treatment of hepatobiliary diseases.

还有研究报道,茵陈蒿与其他中药联合使用用于治疗肺癌。CN108524841A公开了一种治疗肺癌的药物。包括鱼腥草、牡丹皮、夏枯草、仙鹤草、紫草、牡蛎、前胡、女贞子、莪术、菟丝子、白花蛇舌草、川楝子、北沙参、茵陈蒿、百部、麦冬、葶苈子、百合、橘核、山药、紫菀、芦根、海藻、桑白皮、白茅根、阿胶、徐长卿、王不留行按一定重量配比制备而成。There are also studies reporting that Artemisia annua is used in combination with other traditional Chinese medicines for the treatment of lung cancer. CN108524841A discloses a medicine for treating lung cancer. Including Houttuynia cordata, Paeonia suffruticosa, Prunella, Agrimony, Ligusticum comfrey, Oyster, Fore Hu, Ligustrum lucidum, Curcuma, Dodder, Hedyotis diffusa, Chuan Neem, North American ginseng, Artemisia annua, Bai Bu, Ophiopogon japonicus, Tinglizi, lily, orange pit, yam, aster, reed root, seaweed, mulberry bark, Rhizoma Imperatae, donkey-hide gelatin, Xu Changqing and Wang Buliuxing are prepared in a certain weight ratio.

茵陈为菊科植物滨蒿Artemisia scoparia Waldst.et Kit.或茵陈蒿Artemisiacapillaris Thunb.的干燥幼苗。茵陈最早记载于《神农本草经》。“主风湿寒热邪气,热结黄疸”蒙药阿荣目前收载于《内蒙古蒙药材标准》,也被称为茵陈。阿荣可单方用药,也可与其他蒙药配伍用药。单用可清肺、止咳、燥肺脓。Artemisia scoparia is the dry seedling of Artemisia scoparia Waldst.et Kit. or Artemisiacapillaris Thunb. of Compositae. Yinchen was first recorded in "Shen Nong's Materia Medica". "Mainly rheumatism, cold and heat evil, heat causes jaundice" Mongolian medicine Arong is currently included in the "Inner Mongolian Mongolian Medicinal Materials Standard", also known as Yinchen. Arong can be used alone or in combination with other Mongolian medicines. Used alone, it can clear the lung, relieve cough, and dry lung pus.

CN102552663A公开了一种用于治疗百草枯中毒的中药复方,包括蛤蚧、虫草、八角莲、川贝、茵陈、节菖蒲、桂枝、白芍、丝瓜络、旱莲草、乌梅、人参、阿胶、灶心土。虽然该专利文献提到中药复方以活血化瘀、去腐生肌、养肺通络、保肝护肾等中医治疗理论为支持,可以提高脏器自我修复能力和运化功能,抵抗肺纤维化的形成,但该专利文献是利用中药复方的协同作用来治疗百草枯中毒。CN102552663A discloses a traditional Chinese medicine compound for treating paraquat poisoning, including gecko, cordyceps, star anise, Chuanbei, Yinchen, calamus, cassia twig, white peony, loofah, Eclipta, black plum, ginseng, donkey-hide gelatin , stove heart soil. Although the patent document mentions that the traditional Chinese medicine compound is supported by traditional Chinese medicine treatment theories such as promoting blood circulation and removing blood stasis, removing rot and promoting muscle, nourishing the lung and dredging collaterals, protecting the liver and protecting the kidney, etc. Formed, but the patent document is to use the synergy of traditional Chinese medicine to treat paraquat poisoning.

综上可知,未见茵陈蒿作为主要活性成分用于制备治疗肺纤维化的药物的相关报道。To sum up, there is no relevant report on the use of Artemisia annua as the main active ingredient in the preparation of medicines for the treatment of pulmonary fibrosis.

发明内容SUMMARY OF THE INVENTION

本发明的目的在于提供一种茵陈蒿用于制备治疗肺纤维化药物的用途。茵陈蒿能够显著提高SOD的含量,显著降低MDA的含量,并一定程度上可以提高GSH的含量。本发明的目的是通过如下技术方案实现的。The purpose of the present invention is to provide the use of Artemisia annua for preparing a medicine for treating pulmonary fibrosis. Artemisia annua can significantly increase the content of SOD, significantly reduce the content of MDA, and to a certain extent can increase the content of GSH. The object of the present invention is achieved through the following technical solutions.

本发明提供茵陈蒿用于制备治疗肺纤维化药物的用途。The invention provides the use of Artemisia annua for preparing medicine for treating pulmonary fibrosis.

根据本发明所述的用途,优选地,所述茵陈蒿为茵陈蒿药材粉末或茵陈蒿提取物。According to the use of the present invention, preferably, the Artemisia annua is a medicinal powder of Artemisia annua or an Artemisia annua extract.

根据本发明所述的用途,优选地,所述茵陈蒿为茵陈蒿提取物。According to the use of the present invention, preferably, the Artemisia annua is an Artemisia annua extract.

根据本发明所述的用途,优选地,所述药物形成治疗肺纤维化的药物制剂,所述药物制剂包含茵陈蒿,还包含药学上可接受的辅料。According to the use of the present invention, preferably, the drug forms a pharmaceutical preparation for treating pulmonary fibrosis, the pharmaceutical preparation comprises Artemisia annua and pharmaceutically acceptable excipients.

根据本发明所述的用途,优选地,所述茵陈蒿为所述治疗肺纤维化药物中的唯一活性成分。According to the use of the present invention, preferably, the Artemisia annua is the only active ingredient in the medicine for treating pulmonary fibrosis.

根据本发明所述的用途,优选地,所述药物形成用于提高血清中的SOD的含量的药物制剂。According to the use according to the present invention, preferably, the medicament forms a pharmaceutical preparation for increasing the level of SOD in serum.

根据本发明所述的用途,优选地,所述药物形成用于降低血清中的MDA的含量的药物制剂。According to the use according to the present invention, preferably, the medicament forms a pharmaceutical preparation for reducing the content of MDA in serum.

根据本发明所述的用途,优选地,所述茵陈蒿提取物由包括以下的步骤制备而得:According to the purposes of the present invention, preferably, the Artemisia annua extract is prepared by comprising the following steps:

将过筛后的茵陈蒿药材粉末用水浸泡,加热回流提取2~5次,合并水提取液,固液分离,浓缩,得茵陈蒿提取物;其中,每次水的用量为过筛后的茵陈蒿药材粉末质量的8~16倍,每次浸泡的时间为2~6h,每次提取的时间为2~6h。Soak the sieved Artemisia annua medicinal powder in water, heat and reflux for extraction 2 to 5 times, combine the water extracts, separate solid-liquid, and concentrate to obtain Artemisia annua extract; wherein, the amount of water each time is sieved. 8-16 times the quality of the powder of Artemisia annua L., the soaking time is 2-6 hours each time, and the extraction time is 2-6 hours each time.

根据本发明所述的用途,优选地,单位剂量的药物制剂中,茵陈蒿提取物的用量为0.89~4.6g。According to the use of the present invention, preferably, in a unit dose of the pharmaceutical preparation, the dosage of Artemisia annua L. extract is 0.89-4.6 g.

根据本发明所述的用途,优选地,茵陈蒿提取物的用量为1.8~4.3g。According to the use of the present invention, preferably, the dosage of Artemisia annua L. extract is 1.8-4.3 g.

本发明的茵陈蒿用于制备治疗肺纤维化药物,本发明研究发现茵陈蒿可以对气管滴注博来霉素建立的大鼠肺纤维化模型进行干预。茵陈蒿给药后炎症细胞浸润、肺泡间隔增厚、成纤维细胞增生和胶原沉积均有所改善。茵陈蒿能够显著提高SOD的含量,显著降低MDA的含量,并一定程度上可以提高GSH的含量。The Artemisia annua of the present invention is used for preparing a medicine for treating pulmonary fibrosis, and it is found in the research of the present invention that Artemisia annua can interfere with the rat pulmonary fibrosis model established by tracheal instillation of bleomycin. Inflammatory cell infiltration, alveolar septum thickening, fibroblast hyperplasia and collagen deposition were improved after Artemisia annua administration. Artemisia annua can significantly increase the content of SOD, significantly reduce the content of MDA, and to a certain extent can increase the content of GSH.

附图说明Description of drawings

图1为不同用量的茵陈蒿对博来霉素诱导的肺纤维化大鼠HE染色的影响结果。Figure 1 shows the effect of different dosages of Artemisia annua on HE staining of bleomycin-induced pulmonary fibrosis in rats.

图2为不同用量的茵陈蒿对博来霉素诱导的肺纤维化大鼠Masson染色的影响结果。Figure 2 shows the effect of different dosages of Artemisia annua on Masson staining in bleomycin-induced pulmonary fibrosis rats.

图3为检测各个组别中大鼠血清中SOD的含量结果。Figure 3 is the result of detecting the content of SOD in rat serum in each group.

图4为检测各个组别中大鼠血清中GSH的含量结果。Figure 4 shows the results of detecting the content of GSH in rat serum in each group.

图5为检测各个组别中大鼠血清中MDA的含量结果。Figure 5 shows the results of detecting the content of MDA in rat serum in each group.

图1~图5中,CON代表正常对照组,MOD代表模型对照组,ASL代表茵陈蒿低剂量组(100mg/kg),ASM代表茵陈蒿中剂量组(200mg/kg),ASH代表茵陈蒿高剂量组(400mg/kg),PRE代表阳性对照组。In Figures 1 to 5, CON represents the normal control group, MOD represents the model control group, ASL represents the Artemisia annua low-dose group (100 mg/kg), ASM represents the Artemisia annua mid-dose group (200 mg/kg), and ASH represents the Artemisia annua Chenhao high dose group (400mg/kg), PRE represents the positive control group.

具体实施方式Detailed ways

下面结合具体实施例对本发明作进一步的说明,但本发明的保护范围并不限于此。The present invention will be further described below with reference to specific embodiments, but the protection scope of the present invention is not limited thereto.

本发明的茵陈蒿用于制备治疗肺纤维化药物的用途。The use of Artemisia annua of the present invention for preparing a medicine for treating pulmonary fibrosis.

在本发明中,茵陈蒿可以为茵陈蒿药材,比如茵陈蒿药材粉末。茵陈蒿可以为茵陈蒿提取物。In the present invention, Artemisia annua can be a medicinal material of Artemisia annua, such as Artemisia annua medicinal powder. Artemisia annua may be Artemisia annua extract.

根据本发明优选的一个实施方式,茵陈蒿为茵陈蒿提取物。According to a preferred embodiment of the present invention, Artemisia annua is an extract of Artemisia annua.

茵陈蒿提取物的制备方法没有特别限制。根据本发明的一个实施方式,茵陈蒿提取物由包括以下的步骤制备而得:将过筛后的茵陈蒿药材粉末用水加热回流提取2~5次,合并水提取液,固液分离,浓缩,得茵陈蒿提取物;其中,每次水的用量为过筛后的茵陈蒿药材粉末质量的8~16倍,每次提取的时间为2~6h。The preparation method of Artemisia annua extract is not particularly limited. According to one embodiment of the present invention, the Artemisia annua extract is prepared by the following steps: heating and refluxing the sieved Artemisia annua medicinal powder with water for 2 to 5 times, merging the water extracts, solid-liquid separation, Concentrating to obtain Artemisia annua extract; wherein, the amount of water each time is 8 to 16 times the quality of the sieved Artemisia annua medicinal powder, and the extraction time is 2 to 6 hours each time.

在本发明中,可以加热回流提取2~5次,优选为加热回流提取2~4次,更优选为3~4次。每次提取时,水的用量可以为过筛后的茵陈蒿药材粉末质量的8~16倍,优选为8~13倍,更优选为9~11倍。每次提取的时间可以为2~6h,优选为3~6h,更优选为2~5h。In the present invention, heating and reflux extraction may be performed 2 to 5 times, preferably 2 to 4 times of heating and reflux extraction, and more preferably 3 to 4 times. During each extraction, the amount of water used can be 8-16 times, preferably 8-13 times, and more preferably 9-11 times the mass of the sieved Artemisia annua medicinal material powder. The time of each extraction can be 2-6 hours, preferably 3-6 hours, more preferably 2-5 hours.

在本发明中,可以先将所述茵陈蒿药材碾碎后过2号筛。每次提取前,先用水浸泡过筛后的茵陈蒿药材粉末2~6h,优选为3~6h,更优选为3~5h。这样有利于更大程度地提取所需的茵陈蒿提取物。根据本发明的一个具体的实施方式,将茵陈蒿药材碾碎过2号筛,将过筛后的茵陈蒿药材粉末用水浸泡,加热回流提取2~5次,固液分离;合并水提取液并浓缩,得茵陈蒿提取物;其中,每次水的用量为过筛后的茵陈蒿药材粉末质量的8~16倍,每次浸泡的时间为2~6h,每次提取的时间为2~6h。在本发明中,固液分离可以为过滤,过滤时可以采用多层纱布进行,比如三层纱布。在本发明中,所得的茵陈蒿提取物基本不含水。将所得的茵陈蒿提取物放入4~6℃下冷藏,使用时可以加水稀释溶解。In the present invention, the Artemisia annua medicinal material can be crushed first and then passed through a No. 2 sieve. Before each extraction, soak the sieved Artemisia annua medicinal powder in water for 2-6 hours, preferably 3-6 hours, more preferably 3-5 hours. This is beneficial to extract the desired Artemisia annua extract to a greater extent. According to a specific embodiment of the present invention, the medicinal materials of Artemisia annua are crushed and passed through a No. 2 sieve, the sieved Artemisia annua medicinal powder is soaked in water, heated and refluxed for 2 to 5 times of extraction, and solid-liquid separation is performed; combined water extraction The liquid and concentrated to obtain Artemisia annua extract; wherein, the amount of water each time is 8 to 16 times the mass of the sieved Artemisia annua medicinal powder, the soaking time is 2-6 hours each time, and the extraction time is 2-6 hours each time. For 2 ~ 6h. In the present invention, the solid-liquid separation can be filtration, and the filtration can be performed with multiple layers of gauze, such as three layers of gauze. In the present invention, the obtained Artemisia annua extract is substantially free of water. The obtained Artemisia annua extract is refrigerated at 4-6° C., and can be diluted and dissolved by adding water during use.

在本发明中,药物形成治疗肺纤维化的药物制剂,所述药物制剂包含茵陈蒿,还包含药学上可接受的辅料。In the present invention, the drug forms a pharmaceutical preparation for treating pulmonary fibrosis, and the pharmaceutical preparation comprises Artemisia annua and pharmaceutically acceptable excipients.

本发明中,茵陈蒿可以为所述治疗肺纤维化药物中的唯一活性成分。在某些实施方案中,治疗肺纤维化药物以茵陈蒿为唯一活性成分。在另一些实施方案中,治疗肺纤维化药物也可以包含其他具有治疗肺纤维化作用的活性成分,或者包含本身不具有治疗肺纤维化作用、但能够辅助茵陈蒿发挥治疗肺纤维化作用的活性成分。In the present invention, Artemisia annua may be the only active ingredient in the medicine for treating pulmonary fibrosis. In certain embodiments, the drug for the treatment of pulmonary fibrosis has Artemisia annua as the only active ingredient. In other embodiments, the drug for treating pulmonary fibrosis may also contain other active ingredients that have the effect of treating pulmonary fibrosis, or contain other active ingredients that do not have the effect of treating pulmonary fibrosis, but can assist Artemisia annua to play the effect of treating pulmonary fibrosis. Active ingredient.

本发明的药物可以形成用于显著提高血清中的SOD的含量的药物制剂,一定程度上提高血清中的GSH含量。而且,本发明的药物形成用于降低血清中的MDA的含量的药物制剂。SOD是超氧化物歧化酶。GSH是还原型谷胱甘肽。MDA是丙二醛。The medicament of the present invention can form a pharmaceutical preparation for significantly increasing the content of SOD in serum, and to a certain extent, increase the content of GSH in serum. Furthermore, the medicament of the present invention forms a pharmaceutical preparation for reducing the content of MDA in serum. SOD is superoxide dismutase. GSH is reduced glutathione. MDA is malondialdehyde.

SOD是生物体内存在的一种抗氧化金属酶,它能够催化超氧阴离子自由基歧化生成氧和过氧化氢,在机体氧化与抗氧化平衡中起到至关重要的作用。GSH,化学名称为N-(N-L-γ-谷氨酰基-L-半胱氨酰基)甘氨酸,分子式为C10H17N3O6S,分子量为307.33。MDA作为过氧化脂质的降解产物,其含量可体现机体内脂质过氧化的程度,间接反映细胞或机体受损伤的轻重程度。SOD is an antioxidant metalloenzyme existing in organisms, which can catalyze the disproportionation of superoxide anion free radicals to generate oxygen and hydrogen peroxide, and plays a crucial role in the balance of oxidation and antioxidants in the body. GSH, the chemical name is N-(NL-γ-glutamyl-L-cysteinyl)glycine, the molecular formula is C 10 H 17 N 3 O 6 S, and the molecular weight is 307.33. MDA is a degradation product of lipid peroxidation, and its content can reflect the degree of lipid peroxidation in the body, and indirectly reflect the severity of cell or body damage.

本发明中,所述治疗肺纤维化药物可以为原料药,也可以为制剂。所述制剂的剂型可以为任意药用剂型,不做特别限制。优选地,所述剂型为口服剂型。所述口服剂型可以为缓释或控释剂型,例如缓释胶囊剂、缓释片剂等。例如,所述剂型为片剂、丸剂、胶囊剂、颗粒剂、混悬剂等。In the present invention, the drug for treating pulmonary fibrosis may be a raw material drug or a preparation. The dosage form of the preparation can be any pharmaceutical dosage form, and is not particularly limited. Preferably, the dosage form is an oral dosage form. The oral dosage form can be a sustained-release or controlled-release dosage form, such as a sustained-release capsule, a sustained-release tablet, and the like. For example, the dosage forms are tablets, pills, capsules, granules, suspensions, and the like.

在某些实施方案中,所述治疗肺纤维化药物可以包含药学上可接受的辅料。所述药学上可接受的辅料的种类不做限制。当所述药物为口服制剂时,所述辅料可以选自稀释剂、粘合剂、崩解剂和润滑剂中的一种或多种。所述稀释剂包括但不限于甘露醇、微晶纤维素、乳糖、蔗糖、预胶化淀粉或糊精中的一种或多种,优选为微晶纤维素、乳糖或糊精中的一种或多种。所述黏合剂选自甲基纤维素、羧甲基纤维素钠、乙基纤维素、羟丙基纤维素、羟丙基甲基纤维素、明胶、聚维酮或聚乙二醇中的一种或多种,优选为羧甲基纤维素钠、明胶或聚维酮中的一种或多种。所述崩解剂包括但不限于羧甲基淀粉钠、交联羧甲基纤维素钠、交联聚维酮中的一种或多种。所述润滑剂选自聚乙二醇、十二烷基硫酸钠、滑石粉或硬脂酸镁中的一种或多种,优选为交联聚维酮或交联羧甲基纤维素钠。根据本发明一个实施方式,所述药物中的辅料包含微晶纤维素、羧甲基纤维素钠以及交联聚维酮。In certain embodiments, the drug for treating pulmonary fibrosis may comprise pharmaceutically acceptable excipients. The types of the pharmaceutically acceptable excipients are not limited. When the drug is an oral preparation, the adjuvant can be selected from one or more of diluents, binders, disintegrants and lubricants. The diluent includes but is not limited to one or more of mannitol, microcrystalline cellulose, lactose, sucrose, pregelatinized starch or dextrin, preferably one of microcrystalline cellulose, lactose or dextrin or more. The binder is selected from one of methyl cellulose, sodium carboxymethyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, gelatin, povidone or polyethylene glycol. one or more, preferably one or more of sodium carboxymethylcellulose, gelatin or povidone. The disintegrant includes, but is not limited to, one or more of sodium carboxymethyl starch, croscarmellose sodium, and crospovidone. The lubricant is selected from one or more of polyethylene glycol, sodium lauryl sulfate, talc or magnesium stearate, preferably crospovidone or croscarmellose sodium. According to an embodiment of the present invention, the excipients in the medicine comprise microcrystalline cellulose, sodium carboxymethyl cellulose and crospovidone.

本发明中,单位剂量的药物制剂中,茵陈蒿提取物的用量为0.89~4.6g,优选为1.8~4.3g,更优选为1.95~4.1g。根据本发明的一个具体的实施方式,单位剂量的药物制剂中,茵陈蒿提取物的用量为1.92~3.9g。制备的治疗肺纤维化药物中,茵陈蒿的用量在上述范围时,便于服用和发挥功效,并减少副作用。In the present invention, in a unit dose of the pharmaceutical preparation, the dosage of Artemisia annua L. extract is 0.89-4.6 g, preferably 1.8-4.3 g, more preferably 1.95-4.1 g. According to a specific embodiment of the present invention, in a unit dose of the pharmaceutical preparation, the amount of Artemisia annua L. extract is 1.92-3.9 g. In the prepared medicine for treating pulmonary fibrosis, when the dosage of Artemisia annua is within the above range, it is convenient to take and exert its effect, and side effects are reduced.

本发明中的治疗肺纤维化药物的功效可以减少间质内胶原纤维。能够显著提高SOD的含量,显著降低MDA的含量,一定程度上提高GSH的含量。The efficacy of the drug for treating pulmonary fibrosis in the present invention can reduce collagen fibers in the interstitium. It can significantly increase the content of SOD, significantly reduce the content of MDA, and increase the content of GSH to a certain extent.

制备例Preparation example

将茵陈蒿药材碾碎后过2号筛,得到过筛后的茵陈蒿药材粉末;将100g过筛后的茵陈蒿药材粉末用水浸泡,加热回流提取3次;每次水的用量为1000mL,每次浸泡5h,每次加热回流提取4h;合并提取液过滤,减压浓缩,得19.1g茵陈蒿提取物。放入4℃冰箱冷藏,使用时加水稀释溶解。茵陈蒿药材由内蒙古通辽内蒙古民族大学附属医院提供。After crushing the Artemisia annua medicinal material, pass it through a No. 2 sieve to obtain the sieved Artemisia annua medicinal material powder; soak 100 g of the sieved Artemisia annua medicinal material powder in water, and heat and reflux for extraction 3 times; the amount of water each time is: 1000mL, soaked for 5h each time, and heated and refluxed for extraction for 4h each time; the combined extracts were filtered and concentrated under reduced pressure to obtain 19.1g of Artemisia annua extract. Put it in the refrigerator at 4°C, and add water to dissolve it when using. Artemisia annua was provided by the Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia.

实施例1Example 1

1、动物造模及实验方法1. Animal modeling and experimental methods

动物采用健康SD大鼠,体重300~350g,购于长春市亿斯实验动物技术有限责任公司。Animals were healthy SD rats, weighing 300-350 g, purchased from Changchun Yisi Laboratory Animal Technology Co., Ltd.

将大鼠随机分为正常对照组、博来霉素模型对照组(模型对照组)、茵陈蒿给药组(低中高三种剂量,茵陈蒿提取物的用量分别为100mg/kg、200mg/kg、400mg/kg,茵陈蒿提取物为制备例所得)及盐酸泼尼松阳性对照组(5mg/kg),共6组,每组10只。各组均灌胃给药相应受试药,每天1次,直至处死,模型对照组和正常对照组灌胃蒸馏水。除正常对照组外,其余各组通过向气管内一次性注入博来霉素5mg/kg构建大鼠肺纤维化模型;正常对照组采取向气管内一次性注入同体积生理盐水,每组大鼠分别在建模后第14天处死大鼠,取肺组织和血液进行后续实验。The rats were randomly divided into normal control group, bleomycin model control group (model control group), Artemisia annua administration group (low, middle and high doses, and the dosage of Artemisia annua L. extract was 100 mg/kg and 200 mg, respectively. /kg, 400 mg/kg, Artemisia annua extract was obtained in the preparation example) and the positive control group of prednisone hydrochloride (5 mg/kg), a total of 6 groups with 10 animals in each group. Each group was given the corresponding test drug by intragastric administration, once a day, until sacrificed, and the model control group and the normal control group were intragastrically administered with distilled water. Except for the normal control group, the other groups were given a one-time injection of bleomycin 5 mg/kg into the trachea to build a rat pulmonary fibrosis model; the normal control group was given a one-time injection of the same volume of normal saline into the trachea. Rats were sacrificed on the 14th day after modeling, and lung tissue and blood were collected for subsequent experiments.

2、观测指标及其测定方法2. Observation indicators and their measurement methods

肺组织进行HE、Masson染色:将大鼠右肺后叶置于中性福尔马林液中固定,常规石蜡包埋切片进行HE染色和Masson染色以评价肺组织的损伤和肺纤维化程度。HE and Masson staining of lung tissue: The right posterior lobe of the rat lung was fixed in neutral formalin solution, and the conventional paraffin-embedded sections were subjected to HE staining and Masson staining to evaluate the damage of lung tissue and the degree of pulmonary fibrosis.

2.1组织石蜡包埋和切片2.1 Tissue paraffin embedding and sectioning

2.1.1分别取出各组的右肺后叶在4%的多聚甲醛中固定24h;2.1.1 The right posterior lobe of each group was taken out and fixed in 4% paraformaldehyde for 24 hours;

2.1.2吸走多聚甲醛,加入PBS溶液(磷酸盐缓冲液)浸泡,每间隔8小时更换一次,连续72h,4℃保存;2.1.2 Aspirate the paraformaldehyde, add PBS solution (phosphate buffered saline) to soak, replace it every 8 hours, keep it for 72 hours continuously, and store it at 4°C;

2.1.3打开烘箱,将温度设定在62℃,溶解石蜡;2.1.3 Open the oven, set the temperature at 62°C, and dissolve the paraffin;

2.1.4将各个肺组织切成0.2~0.3cm的小块,然后用酒精梯度进行脱水(酒精的浓度为30%、50%、70%、80%、90%、95%、100%),每隔30min更换一次;2.1.4 Cut each lung tissue into small pieces of 0.2-0.3 cm, and then dehydrate with alcohol gradient (the concentration of alcohol is 30%, 50%, 70%, 80%, 90%, 95%, 100%), Replace every 30min;

2.1.5放入50%酒精+50%二甲苯溶液30min后取出,然后放入二甲苯中注意观察肺组织块至透明;2.1.5 Put in 50% alcohol + 50% xylene solution for 30 minutes, take it out, and then put it in xylene to observe the lung tissue block until it is transparent;

2.1.6放入预融50%酒精+50%二甲苯30min,然后分别放入预融的石蜡两次,每次2h;2.1.6 Put in pre-melted 50% alcohol + 50% xylene for 30min, then put in pre-melted paraffin twice, 2h each time;

2.1.7放入预融100%石蜡纸盒内凝固,4℃存放;2.1.7 Put it into a pre-melted 100% paraffin carton to solidify, and store it at 4°C;

2.1.8用切片机将组织切成5~10μM厚的连续切片,将切片平展放置于平板上,光面朝上;2.1.8 Use a microtome to cut the tissue into continuous slices with a thickness of 5-10 μM, and place the slices flat on a flat plate with the smooth side facing up;

2.1.9将石蜡薄切片放于水面上(水温40℃),使其伸展,然后贴在预先处理好的玻片上;2.1.9 Put the paraffin thin section on the water surface (water temperature 40℃), stretch it, and then stick it on the pre-treated glass slide;

2.1.10 40℃烘烤,过夜,以备染色。2.1.10 Bake at 40℃ overnight for staining.

2.2HE染色步骤2.2 HE staining steps

2.2.1烤片:80℃恒温箱中放置1h;2.2.1 Baking slices: placed in an 80°C incubator for 1 hour;

2.2.2脱蜡:二甲苯I脱蜡10min、二甲苯II脱蜡20min;2.2.2 Dewaxing: dewaxing xylene I for 10 min, dewaxing xylene II for 20 min;

2.2.3脱水:100%乙醇5min脱水2次,95%乙醇5min脱水2次,85%乙醇中放置约1min,75%乙醇中放置约1min,以吸水纸吸干液体;2.2.3 Dehydration: dehydrate twice in 100% ethanol for 5 min, dehydrate twice in 95% ethanol for 5 min, place in 85% ethanol for about 1 min, and place in 75% ethanol for about 1 min, and dry the liquid with absorbent paper;

2.2.4冲洗:蒸馏水冲洗2min,冲洗两次;2.2.4 Rinse: rinse with distilled water for 2 minutes, rinse twice;

2.2.5染色:苏木素染色5min;2.2.5 Staining: hematoxylin staining for 5min;

2.2.6用自来水稍微冲洗;2.2.6 Rinse slightly with tap water;

2.2.7分化:1%盐酸酒精溶液浸润5~10s(观察切片由蓝变红);2.2.7 Differentiation: infiltrate with 1% hydrochloric acid alcohol solution for 5-10s (observe the slice from blue to red);

2.2.8返蓝:自来水洗25min左右;2.2.8 Back to blue: wash with tap water for about 25min;

2.2.9 0.5%伊红染色2min;2.2.9 0.5% eosin staining for 2min;

2.2.10 95%乙醇5min脱水2次,用吸水纸吸干液体;2.2.10 Dehydrate 2 times in 95% ethanol for 5 min, and dry the liquid with absorbent paper;

2.2.11 100%乙醇5min脱水2次,用吸水纸吸干液体;2.2.11 Dehydrate twice in 100% ethanol for 5 min, and dry the liquid with absorbent paper;

2.2.12二甲苯中透明5min两次,用吸水纸吸干液体;2.2.12 Transparent in xylene for 5min twice, and dry the liquid with absorbent paper;

2.2.13中性树胶封固、镜下观察。2.2.13 Neutral gum sealing and observation under microscope.

2.3Masson染色步骤2.3 Masson staining steps

2.3.1肺组织切片常规脱蜡至水;2.3.1 Routine dewaxing of lung tissue sections to water;

2.3.2Masson复合染液染色5~10min;2.3.2 Masson compound dyeing solution for 5-10min;

2.3.3置于2%冰醋酸水溶液浸洗片刻;2.3.3 Immerse in 2% glacial acetic acid aqueous solution for a while;

2.3.4置于1%磷酸水溶液中3~5min后甩干;2.3.4 Put in 1% phosphoric acid aqueous solution for 3 to 5 minutes and then spin dry;

2.3.5用苯胺蓝水溶液染色5min;2.3.5 Stain with aniline blue aqueous solution for 5min;

2.3.6酒精梯度脱水,二甲苯I、II透明,中性树胶封片。2.3.6 Alcohol gradient dehydration, Xylene I and II are transparent, and neutral gum is used for sealing.

2.4血清中MDA含量检测(硫代巴比妥酸法)2.4 Detection of MDA content in serum (thiobarbituric acid method)

2.4.1测试原理:MDA(丙二醛)可与硫代巴比妥酸(TBA)相结合而形成红色产物。该产物于532nm处有最大吸收峰。由于该反应的底物为TBA,所以该检测方法也称为TBA法。2.4.1 Test principle: MDA (malondialdehyde) can combine with thiobarbituric acid (TBA) to form a red product. The product has an absorption maximum at 532 nm. Since the substrate of this reaction is TBA, this detection method is also called TBA method.

2.4.2操作步骤:2.4.2 Operation steps:

(1)设定空白管、标准管、测定管,空白管中加入100μl无水乙醇,标准管中加入100μl标准品(四乙氧基丙烷10nmol/ml),测定管中加入100μl待测样品。(1) Set up blank tube, standard tube and measuring tube. Add 100 μl of absolute ethanol to the blank tube, add 100 μl of standard substance (tetraethoxypropane 10nmol/ml) to the standard tube, and add 100 μl of the sample to be tested to the measuring tube.

(2)加入100μl试剂一,涡旋混匀1min。(2) Add 100 μl of Reagent 1, vortex and mix for 1 min.

(3)分别加入1.5ml试剂二和试剂三涡旋混匀。(3) Add 1.5ml of Reagent 2 and Reagent 3 respectively and mix by vortexing.

(4)95%恒温水浴40min,取出试管以流水冷却,在室温3500rpm离心10min吸取上清液加入96孔板,每孔200μl,每个样本设置3个复孔。532nm处测定OD值,取均值作为测定OD值。(4) 95% constant temperature water bath for 40min, take out the test tube and cool with running water, centrifuge at 3500rpm for 10min at room temperature, suck the supernatant and add it to 96-well plate, 200μl per well, and set 3 duplicate wells for each sample. The OD value was measured at 532 nm, and the average value was taken as the measured OD value.

以双蒸水调零。Zero with double distilled water.

*因样本不存在溶血、脂血现象,故标准管及空白管每批只做2个样本,同时以空白管来代替对照管。该操作步骤中,采用试剂盒进行检测,该试剂盒购自南京建成生物工程研究所,型号为A003-1-2。*Because there is no hemolysis and lipid blood in the samples, only 2 samples are made in each batch of standard tubes and blank tubes, and blank tubes are used instead of control tubes. In this operation step, a kit was used for detection, and the kit was purchased from Nanjing Jiancheng Bioengineering Institute, model A003-1-2.

2.5血清中SOD含量检测(WST-1法)2.5 Detection of SOD content in serum (WST-1 method)

2.5.1操作步骤2.5.1 Operation steps

(1)设定对照空、对照空白孔、测定孔和测定空白孔,对照孔和对照空白孔中加入20μl双蒸水,测定孔和测定空白孔中加入20μl待测样品。(1) Set control blank, control blank well, assay well and assay blank well, add 20 μl of double distilled water to the control well and control blank well, and add 20 μl of the sample to be tested to the assay well and assay blank well.

(2)在对照空白孔和测定空白孔中加入20μl酶稀释液,在对照孔和测定空中加入20μl酶工作液。(2) Add 20 μl of enzyme diluent to the control blank wells and assay blank wells, and add 20 μl of enzyme working solution to the control wells and assay air.

(3)加入200μl底物应用液,涡旋混匀,37℃孵育20min,450nm处测定OD值。(3) Add 200 μl of substrate application solution, vortex to mix, incubate at 37° C. for 20 min, and measure the OD value at 450 nm.

该操作步骤中,采用试剂盒进行检测,该试剂盒购自南京建成生物工程研究所,型号为A001-3-2。In this operation step, a kit was used for detection, and the kit was purchased from Nanjing Jiancheng Bioengineering Institute, model A001-3-2.

2.6血清中GSH含量检测(比色法)2.6 Detection of GSH content in serum (colorimetric method)

2.6.1操作步骤2.6.1 Operation steps

(1)设定空白孔、标准孔和测定孔,空白孔加入100μl试剂一(贮备液),标准孔中加入100μl标准品(20μM GSH标准溶液),测定孔中加入100μl待测样品(上清液)。(1) Set blank wells, standard wells and assay wells, add 100 μl of reagent 1 (stock solution) to the blank wells, add 100 μl of standard (20 μM GSH standard solution) to the standard wells, and add 100 μl of the sample to be tested (supernatant) to the assay wells liquid).

(2)分别加入100μl试剂二和25μl的试剂三。(2) Add 100 μl of reagent two and 25 μl of reagent three, respectively.

(3)混匀,静置5min,405nm处酶标仪测定各孔吸光度值。(3) Mix well, let stand for 5 min, and measure the absorbance value of each well with a microplate reader at 405 nm.

该操作步骤中,采用试剂盒进行检测,该试剂盒购自南京建成生物工程研究所,型号为A006-2-1。In this operation step, a kit was used for detection, and the kit was purchased from Nanjing Jiancheng Bioengineering Institute, model A006-2-1.

3、实验结果3. Experimental results

3.1利用肺组织HE染色评价茵陈蒿对肺纤维化大鼠的改善作用3.1 Evaluation of the improvement effect of Artemisia annua on pulmonary fibrosis rats by HE staining of lung tissue

图1为不同浓度的茵陈蒿对博来霉素诱导的肺纤维化大鼠HE染色的影响结果。如图1所示,正常对照组大鼠肺泡形态正常,壁纤细,未见肺间质中有炎症细胞浸润。模型对照组中,博来霉素给药后即出现肺泡间隔增厚,可见炎细胞浸润;可见片状实变,实变区有较多炎细胞浸润、成纤维细胞增生和胶原沉积。茵陈蒿给药组(茵陈蒿低剂量组、中剂量组和高剂量组)中,可以看出茵陈蒿给药后炎症细胞浸润、肺泡间隔增厚、成纤维细胞增生和胶原沉积均有所改善。Figure 1 shows the effect of different concentrations of Artemisia annua on HE staining of bleomycin-induced pulmonary fibrosis in rats. As shown in Figure 1, the alveolar shape of the normal control group was normal, the wall was slender, and there was no inflammatory cell infiltration in the pulmonary interstitium. In the model control group, the alveolar septum thickened immediately after bleomycin administration, and inflammatory cell infiltration was seen; sheet-like consolidation was seen, with more inflammatory cell infiltration, fibroblast proliferation and collagen deposition in the consolidation area. In the Artemisia annua administration group (low-dose group, middle-dose group and high-dose group of Artemisia annua), it can be seen that inflammatory cell infiltration, alveolar septum thickening, fibroblast hyperplasia and collagen deposition were all affected by Artemisia annua administration. it has been improved.

3.2利用肺组织Masson染色评价茵陈蒿对肺纤维化大鼠的改善作用3.2 Using Masson staining of lung tissue to evaluate the improving effect of Artemisia annua on pulmonary fibrosis in rats

图2为不同浓度的茵陈蒿对博来霉素诱导的肺纤维化大鼠Masson染色的影响结果。Figure 2 shows the effect of different concentrations of Artemisia annua on Masson staining in bleomycin-induced pulmonary fibrosis rats.

如图2所示,正常对照组大鼠肺组织肺泡结构基本正常。模型对照组中,博来霉素造模后的各组出现不同程度的肺组织纤维化,其中以模型对照组肺组织肺泡塌陷、融合,肺泡壁增宽,间质内胶原纤维增多明显。茵陈蒿给药组(茵陈蒿低剂量组、茵陈蒿中剂量组和茵陈蒿高剂量组)的肺泡结构部分破坏,肺泡壁增宽增厚,胶原纤维增多均有所改善。茵陈蒿给药组与模型对照组相比,间质内胶原纤维增加较少。茵陈蒿低剂量组、茵陈蒿中剂量组和茵陈蒿高剂量组的都能够明显改善博来霉素造模诱导的肺纤维化,与阳性对照组相比,茵陈蒿中剂量给药组效果更好。As shown in Figure 2, the alveolar structure of the lung tissue of the rats in the normal control group was basically normal. In the model control group, different degrees of lung tissue fibrosis occurred in each group after bleomycin modeling. In the model control group, the alveoli of the lung tissue collapsed and fused, the alveolar wall widened, and the collagen fibers in the interstitium increased significantly. In the Artemisia annua administration group (the Artemisia annua low-dose group, the Artemisia annua medium-dose group, and the Artemisia annua high-dose group), the alveolar structure was partially destroyed, the alveolar walls were widened and thickened, and the collagen fibers increased. Compared with the model control group, the interstitial collagen fibers increased less in the Artemisia annua administration group. Artemisia annua low-dose group, Artemisia annua mid-dose group, and Artemisia annua high-dose group can significantly improve bleomycin-induced pulmonary fibrosis. The drug group was more effective.

3.3检测大鼠血清中SOD、GSH和MDA的含量3.3 Detection of SOD, GSH and MDA content in rat serum

图3为检测各个组别中大鼠血清中SOD的含量结果。图4为检测各个组别中大鼠血清中GSH的含量结果。图5为检测各个组别中大鼠血清中MDA的含量结果。各个组别指的是正常对照组、模型对照组、茵陈蒿低剂量组、茵陈蒿中剂量组、茵陈蒿高剂量组和阳性对照组。Figure 3 is the result of detecting the content of SOD in rat serum in each group. Figure 4 shows the results of detecting the content of GSH in rat serum in each group. Figure 5 shows the results of detecting the content of MDA in rat serum in each group. Each group refers to the normal control group, the model control group, the low-dose group of Artemisia annua, the medium-dose group of Artemisia annua, the high-dose group of Artemisia annua and the positive control group.

图3、图4和图5中##代表正常组和模型组有显著性差异,P<0.01,#代表正常组和模型组有显著性差异,P<0.05,**给药组与模型组有显著性差异,P<0.01。In Figure 3, Figure 4 and Figure 5, ## represents a significant difference between the normal group and the model group, P<0.01, # represents a significant difference between the normal group and the model group, P<0.05, ** the administration group and the model group There was significant difference, P<0.01.

当机体受损时,系统会产生大量氧自由基。这些氧自由基进而攻击生物膜中的多不饱和脂肪酸引起脂质过氧化,形成脂质过氧化物及新的氧自由基等,造成组织细胞的损伤。MDA作为过氧化脂质的降解产物,其含量可体现机体内脂质过氧化的程度,间接反映细胞或机体受损伤的轻重程度。When the body is damaged, the system will produce a large number of oxygen free radicals. These oxygen free radicals then attack the polyunsaturated fatty acids in the biofilm, causing lipid peroxidation, forming lipid peroxides and new oxygen free radicals, etc., causing tissue and cell damage. MDA is a degradation product of lipid peroxidation, and its content can reflect the degree of lipid peroxidation in the body, and indirectly reflect the severity of cell or body damage.

抗氧化剂也被运用于肺间质纤维化的治疗中。Antioxidants are also used in the treatment of pulmonary fibrosis.

SOD具有抗自由基损伤的能力,其活力的高低可间接反映机体清除氧自由基的能力及组织氧化反应的严重程度。GSH(谷胱甘肽)是体内存在的一种清除自由基的系统,在一些病理状况下谷胱甘肽过氧化物酶的活力会发生明显变化。SOD has the ability to resist free radical damage, and the level of its activity can indirectly reflect the body's ability to scavenge oxygen free radicals and the severity of tissue oxidation. GSH (glutathione) is a system for scavenging free radicals in the body. In some pathological conditions, the activity of glutathione peroxidase will change significantly.

由图3可知,茵陈蒿低剂量组、中剂量组和高剂量组均能明显提高SOD的含量。其中,茵陈蒿中剂量组和高剂量组对提高SOD含量的效果超过了阳性对照组。It can be seen from Figure 3 that the low-dose, middle-dose and high-dose groups of Artemisia annua can significantly increase the content of SOD. Among them, the effect of the middle-dose group and the high-dose group of Artemisia annua on improving SOD content exceeded that of the positive control group.

由图4可知,茵陈蒿低剂量组、中剂量组和高剂量组能够略微提高GSH的含量,明显不如阳性对照组的效果好。It can be seen from Figure 4 that the low-dose group, middle-dose group and high-dose group of Artemisia annua can slightly increase the content of GSH, which is obviously not as good as that of the positive control group.

由图5可知,茵陈蒿中剂量组能够显著降低MDA的含量。茵陈蒿低剂量组几乎无法降低MDA的含量,茵陈蒿高剂量组仅能稍微降低MDA的含量,低中高剂量组并未表现明显的量效关系,可能与高剂量的剂量高有关,药物剂量过高可能使对MDA的作用降低。It can be seen from Figure 5 that the middle-dose group of Artemisia annua can significantly reduce the content of MDA. Artemisia annua low-dose group could hardly reduce MDA content, Artemisia annua high-dose group could only slightly reduce MDA content, low-medium-high-dose group did not show a significant dose-effect relationship, which may be related to high-dose, high-dose drug. Too high a dose may reduce the effect on MDA.

以上结果说明茵陈蒿能够改善博来霉素诱导的肺纤维化程度,而且我们初步推断其改善肺纤维化的机制可能与抗氧化有关。并且茵陈蒿高剂量组在提高SOD含量方面的效果最优,超过了阳性对照组的结果。茵陈蒿中剂量组在降低MDA含量方面效果最优。The above results indicate that Artemisia annua can improve the degree of bleomycin-induced pulmonary fibrosis, and we preliminarily infer that the mechanism of improving pulmonary fibrosis may be related to antioxidant. And Artemisia annua high-dose group had the best effect in increasing SOD content, surpassing the results of the positive control group. The middle-dose group of Artemisia annua had the best effect in reducing the content of MDA.

本发明并不限于上述实施方式,在不背离本发明的实质内容的情况下,本领域技术人员可以想到的任何变形、改进、替换均落入本发明的范围。The present invention is not limited to the above-mentioned embodiments, and any modifications, improvements and substitutions that can be conceived by those skilled in the art without departing from the essence of the present invention fall into the scope of the present invention.

Claims (7)

1.茵陈蒿用于制备治疗肺纤维化药物的用途,1. The purposes of Artemisia annua for the preparation of medicines for the treatment of pulmonary fibrosis, 所述茵陈蒿为茵陈蒿提取物;所述茵陈蒿提取物由包括以下的步骤制备而得:Described Artemisia annua is Artemisia annua extract; Described Artemisia annua extract is prepared by comprising the following steps: 将过筛后的茵陈蒿药材粉末用水浸泡,加热回流提取2~5次,合并水提取液,固液分离,浓缩,得茵陈蒿提取物;其中,每次水的用量为过筛后的茵陈蒿药材粉末质量的8~16倍,每次浸泡的时间为2~6h,每次提取的时间为2~6h。Soak the sieved Artemisia annua medicinal powder in water, heat and reflux for extraction 2 to 5 times, combine the water extracts, separate solid-liquid, and concentrate to obtain Artemisia annua extract; wherein, the amount of water each time is sieved. 8-16 times the quality of the powder of Artemisia annua L., the soaking time is 2-6 hours each time, and the extraction time is 2-6 hours each time. 2.根据权利要求1的用途,其特征在于,所述药物形成治疗肺纤维化的药物制剂,所述药物制剂包含茵陈蒿,还包含药学上可接受的辅料。2 . The use according to claim 1 , wherein the medicine forms a pharmaceutical preparation for treating pulmonary fibrosis, the pharmaceutical preparation comprises Artemisia annua and pharmaceutically acceptable excipients. 3 . 3.根据权利要求2的用途,其特征在于,所述茵陈蒿为所述治疗肺纤维化药物中的唯一活性成分。3. The use according to claim 2, wherein the Artemisia annua is the only active ingredient in the medicine for treating pulmonary fibrosis. 4.根据权利要求3所述的用途,其特征在于,所述药物形成用于提高血清中的SOD的含量的药物制剂。4. The use according to claim 3, wherein the medicament forms a pharmaceutical preparation for increasing the level of SOD in serum. 5.根据权利要求4所述的用途,其特征在于,所述药物形成用于降低血清中的MDA的含量的药物制剂。5. The use according to claim 4, wherein the medicament forms a pharmaceutical preparation for reducing the content of MDA in serum. 6.根据权利要求1所述的用途,其特征在于,单位剂量的药物制剂中,茵陈蒿提取物的用量为0.89~4.6g。6 . The use according to claim 1 , wherein, in the pharmaceutical preparation of a unit dose, the amount of Artemisia annua L. extract is 0.89-4.6 g. 7 . 7.根据权利要求6所述的用途,其特征在于,茵陈蒿提取物的用量为1.8~4.3g。7 . The use according to claim 6 , wherein the amount of Artemisia annua L. extract is 1.8-4.3 g. 8 .
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* Cited by examiner, † Cited by third party
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CN102038852A (en) * 2009-10-15 2011-05-04 陈向阳 Healthy tea for treating old lung disease and preparation method thereof
CN102552663A (en) * 2011-10-15 2012-07-11 王吉坤 Chinese herbal compound used for treating paraquat poisoning

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* Cited by examiner, † Cited by third party
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CN102038852A (en) * 2009-10-15 2011-05-04 陈向阳 Healthy tea for treating old lung disease and preparation method thereof
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