CN1759855A - 一种治疗慢性肝炎的药物 - Google Patents
一种治疗慢性肝炎的药物 Download PDFInfo
- Publication number
- CN1759855A CN1759855A CN 200410064999 CN200410064999A CN1759855A CN 1759855 A CN1759855 A CN 1759855A CN 200410064999 CN200410064999 CN 200410064999 CN 200410064999 A CN200410064999 A CN 200410064999A CN 1759855 A CN1759855 A CN 1759855A
- Authority
- CN
- China
- Prior art keywords
- total
- radix astragali
- tanshinone
- liver
- effective site
- 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
- 239000003814 drug Substances 0.000 title claims abstract description 14
- 208000006454 hepatitis Diseases 0.000 title claims abstract description 14
- 206010008909 Chronic Hepatitis Diseases 0.000 title claims abstract description 13
- 229940079593 drug Drugs 0.000 title description 3
- 229930182490 saponin Natural products 0.000 claims abstract description 20
- 150000007949 saponins Chemical class 0.000 claims abstract description 20
- AIGAZQPHXLWMOJ-UHFFFAOYSA-N Tanshinone I Chemical compound C1=CC2=C(C)C=CC=C2C(C(=O)C2=O)=C1C1=C2C(C)=CO1 AIGAZQPHXLWMOJ-UHFFFAOYSA-N 0.000 claims description 34
- 239000009636 Huang Qi Substances 0.000 claims description 22
- 229930183118 Tanshinone Natural products 0.000 claims description 19
- 235000017709 saponins Nutrition 0.000 claims description 19
- 150000007965 phenolic acids Chemical class 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 9
- 239000000287 crude extract Substances 0.000 claims description 8
- 239000001397 quillaja saponaria molina bark Substances 0.000 abstract description 6
- 241001061264 Astragalus Species 0.000 abstract description 3
- 235000006533 astragalus Nutrition 0.000 abstract description 3
- 239000002253 acid Substances 0.000 abstract description 2
- 240000007164 Salvia officinalis Species 0.000 abstract 1
- 229940107666 astragalus root Drugs 0.000 abstract 1
- 235000005412 red sage Nutrition 0.000 abstract 1
- 210000004233 talus Anatomy 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 10
- 206010019668 Hepatic fibrosis Diseases 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 208000019425 cirrhosis of liver Diseases 0.000 description 8
- 210000004185 liver Anatomy 0.000 description 8
- 241000700159 Rattus Species 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000003463 adsorbent Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- 210000000952 spleen Anatomy 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 208000002672 hepatitis B Diseases 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 208000019423 liver disease Diseases 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 206010067125 Liver injury Diseases 0.000 description 3
- 241001072909 Salvia Species 0.000 description 3
- 235000017276 Salvia Nutrition 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 230000002440 hepatic effect Effects 0.000 description 3
- 230000003285 pharmacodynamic effect Effects 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000013558 reference substance Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 239000007901 soft capsule Substances 0.000 description 3
- 238000012360 testing method Methods 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
- IBGBGRVKPALMCQ-UHFFFAOYSA-N 3,4-dihydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1O IBGBGRVKPALMCQ-UHFFFAOYSA-N 0.000 description 2
- 235000010110 Astragalus glycyphyllos Nutrition 0.000 description 2
- 208000000419 Chronic Hepatitis B Diseases 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 208000004930 Fatty Liver Diseases 0.000 description 2
- 206010019708 Hepatic steatosis Diseases 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 206010023126 Jaundice Diseases 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 230000003064 anti-oxidating effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 208000010706 fatty liver disease Diseases 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 231100000234 hepatic damage Toxicity 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000008818 liver damage Effects 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 150000002989 phenols Chemical class 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000002798 spectrophotometry method Methods 0.000 description 2
- 231100000240 steatosis hepatitis Toxicity 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 239000002023 wood Substances 0.000 description 2
- SMDOOINVMJSDPS-UHFFFAOYSA-N Astragaloside Natural products C1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)OC2C(C(OC3C(C(O)C(O)C(CO)O3)O)C(O)C(CO)O2)O)=C1 SMDOOINVMJSDPS-UHFFFAOYSA-N 0.000 description 1
- 238000007445 Chromatographic isolation Methods 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 206010019755 Hepatitis chronic active Diseases 0.000 description 1
- 206010019759 Hepatitis chronic persistent Diseases 0.000 description 1
- 206010019786 Hepatitis non-A non-B Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 206010041660 Splenomegaly Diseases 0.000 description 1
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 231100000354 acute hepatitis Toxicity 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 208000010002 alcoholic liver cirrhosis Diseases 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 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
- QMNWISYXSJWHRY-XWJCTJPOSA-N astragaloside Chemical compound O1[C@H](C(C)(O)C)CC[C@]1(C)[C@@H]1[C@@]2(C)CC[C@]34C[C@]4(CC[C@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)CO4)O)C4(C)C)C4[C@@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)CC3[C@]2(C)C[C@@H]1O QMNWISYXSJWHRY-XWJCTJPOSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000002481 ethanol extraction Methods 0.000 description 1
- 239000000469 ethanolic extract Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002212 flavone derivatives Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 208000013210 hematogenous Diseases 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 206010019692 hepatic necrosis Diseases 0.000 description 1
- 230000007866 hepatic necrosis Effects 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 230000007365 immunoregulation Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 235000009048 phenolic acids Nutrition 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 229960003371 protocatechualdehyde Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
一种治疗慢性肝炎的药物，是由黄芪、丹参的粗提物中分离出的有效部位构成的组合物，各有效部位总酚酸、总丹参酮和黄芪总皂苷的质量比为15～50∶3～7∶0.5～4。经药效学试验表明，本发明明显减轻大鼠CCl4所致的肝细胞坏死、肝组织纤维化和肝硬化的程度，其抗肝组织纤维化作用在防治慢性肝炎中具有重要意义。
Description
一、技术领域
本发明涉及一种治疗慢性肝炎的药物组合物，特别是涉及以植物中草药的有效部位为原料制备的治疗慢性肝炎的药物。
二、背景技术
病毒性肝炎临床表现可分为急性肝炎与慢性肝炎两大类型。根据临床表现差异，慢性肝炎又可分为以下数种临床类型：
慢性迁延性肝炎：病程超过半年以上，症状轻，无黄疸或黄疸轻微。肝脏轻度肿大，质地中等偏软，脾脏一般不可触及，肝功能改变以单项ALT波动为特点。一般无肝外器官表现。
慢性活动性肝炎：病程超过半年，症状较重，慢性肝病面容，肝脏大而质地中等偏硬，多数脾大，肝功能损害明显，ALT持续或反复升高，血浆白蛋白低下，或白/球蛋白比例降低等表现。
慢性肝炎病程冗长，临床演变并发症较多。其中重要有：①肝炎后脂肪肝，以超声滤检查显大特殊脂肪肝波形为主要表现。②肝硬化：乙型肝炎、非甲非乙型肝炎可演变为坏死后性、胆汁性或门静脉性肝硬化。
我国为乙型肝炎的高发区，有60％的人群受过乙肝病毒的感染，乙型肝炎表面抗原(HBsAg)携带者约为1.3亿人。目前我国患慢性乙型肝炎的病人超过3000万，其中不少人可能发展成肝硬化或肝癌。每年我国死于乙肝后肝硬化、肝癌者达40万人。因此慢性乙型肝炎的治疗(包括能阻断、减轻乃至逆转肝纤维化的治疗)是我国迫切需要解决的重大疾病之一。有专家认为“谁控制了肝纤维化，谁就控制了慢性肝炎”。
从70年代中期以来，随着人们对肝纤维化发生、发展认识的不断深化，现已公认肝纤维化是细胞外基质的合成与降解失去平衡的结果，故纤维组织的形成可看作是一个动态过程，并证明人类的肝纤维化是可以逆转的。多年来，我国医务工作者不断致力于中医中药治疗慢性肝炎和逆转肝纤维化的研究，取得了可喜的成绩，这是中医中药在肝病治疗上的一大优势。大量文献资料表明，中医中药在抗肝纤维化方面以其可靠的疗效和较少的副作用而独树一帜。目前国内外有关肝纤维化治疗的研究多处于实验阶段，尚缺乏有治疗前景的逆转肝纤维化或肝硬化的药物。
《医家金》曰：“肝为木气，全赖土以滋培，以水灌溉，若中土虚则木不升而郁”。湿为阴邪，最易伤阳，脾阳受困，而致脾亏气虚。气虚失运，木郁失达，则肝部气滞。气滞日久，气病及血，血行不畅，瘀血内阻，络道失和，以致痞块形成，青筋暴露，病至险境，缠绵难愈。针对病机所在，治法当以黄芪益气扶脾为重，丹参活血化瘀为先，缓缓图治，以收远效。黄芪和丹参自古以来就是治疗肝病的主要中药。近年来国内众多学者对其药理学、药效学等进行了广泛深入的研究，并开发了以黄芪、丹参为主要原料的口服液、注射液、针剂等药物以治疗肝病。但这些药物大多使用黄芪、丹参的粗提物。
三、发明内容
黄芪药材中含有多糖、皂苷、黄酮、氨基酸、酚类和微量元素等，其中多糖和皂苷为免疫调节作用的主要活性成分。丹参药材中所含的丹参酮和酚酸类是其药理作用的主要活性成分。本发明首先对黄芪、丹参进行提取得到粗提物，然后自粗提物中分离出主要含黄芪总皂苷、总丹参酮和总酚酸的各有效部位，最后将各有效部位按一定比例混合均匀得到组合物。该组合物可以按公知的工艺加工成口服制剂，如颗粒剂、片剂、胶囊等。其特征在于：组合物中主要含总酚酸、总丹参酮和黄芪总皂苷的各有效部位有以下质量比：
总酚酸∶总丹参酮∶黄芪总皂苷＝15～50∶3～7∶0.5～4。
优选的质量比为：
总酚酸∶总丹参酮∶黄芪总皂苷＝20～45∶4～6∶1～3。
最佳的质量比为：
总酚酸∶总丹参酮∶黄芪总皂苷＝25∶3.5∶2。
各有效部位中，总酚酸、总丹参酮和黄芪总皂苷的含量均≥50％。
黄芪皂苷既溶于水又溶于乙醇。用水或乙醇对黄芪进行提取得到水或乙醇的粗提物，然后自粗提物中分离出主要含黄芪总皂苷的有效部位。
丹参酮为脂溶性成分，酚酸为水溶性成分。丹参药材分别用乙醇和水进行提取，得到乙醇和水的粗提物，然后自粗提物分离得到主要含总丹参酮和总酚酸的有效部位。
所述的分离主要是吸附分离，如薄层分离、色谱分离、大孔吸附树脂分离等。
安徽医科大学对上述各有效部位进行了体内外药效学试验，证明了本发明的提取、分离工艺的可行性。同时对各有效部位按比例混合后的组合物亦进行了体内外药效学试验(试验中，组合物编号为CAE)，如果如下：
CAE体外对HSC-T6细胞功能的抑制作用
体外实验结果表明，在60.3mg·L-1～mg·L-1浓度范围内，CAE对HSC-T6细胞增殖和产生胶原有浓度依赖性的抑制作用。提示CAE对HSC上述功能有直接抑制作用。
CAE体外对巨噬细胞功能的抑制作用
实验结果表明，CAE在5.9～94.2mg·L-1浓度范围内，对LPS诱导大鼠PMΦs产生IL-1、NO和TNF-α也有明显的浓度依赖性。提示CAE对PMΦs产生炎性细胞因子有直接的抑制作用。
CAE对小鼠D-GaIN性肝损伤的保护作用
采用D-GaIN(800mg·L-1)诱导小鼠急性肝损伤模型，CAE三个剂量(60、120、240mg·L-1)对D-GaIN升高的血清ALT水平、肝脏指数以及肝匀浆MDA的含量均显著降低。表明CAE对D-GaIN致小鼠急性肝损伤有明显的保护作用，并提示其作用可能与该药的抗氧化作用有关。
CAE对CCl4致大鼠肝纤维化的防治作用
实验结果表明，对CCl4致大鼠肝纤维化模型，CAE三个剂量(60、120、240gmg·kg-1×8wk)不仅可降低CCl4升高的ALT与AST水平和CCl4升高的大鼠肝、脾指数，以及肝组织MDA水平；还可升高CCl4降低的大鼠胸腺指数和肝组织T-SOD水平，而且可显著降低CCl4升高的血清HA含量和肝组织HYP含量。病理组织学发现，CAE明显减轻CCl4所致的肝细胞坏死、肝组织纤维化和肝硬化的程度。表明CAE有抗肝纤维化作用，该作用可能与其抗氧化和抗炎作用有关。
总之，CAE体外对HSC-T6细胞的增殖和产生胶原均有明显的抑制作用；大鼠腹腔巨噬细胞产生IL-1、TNF-α和NO等炎性因子亦有明显的抑制作用；对小鼠D- GaIN性肝损伤，CAE三个剂量均有明显的保护作用；对大鼠CCl4性肝纤维化模型，CAE三个剂量亦有明显的防治作用。
四、具体实施方式
现以大孔吸附树脂吸附分离为例，非限定实施例叙述如下。
1、黄芪总皂苷的制备：
黄芪药材粉碎后用70～85％的乙醇回流提取两次，第一次10倍量，回流1～2小时，第二次8倍量，回流1小时，合并两次滤液，减压蒸馏，回收乙醇，当乙醇脱尽时，加水溶解，静置12小时，分离，用D101大孔吸附树脂吸附分离，分别用水、30％、70％乙醇洗脱，减压浓缩70％乙醇洗脱液，60℃真空干燥得到主要含黄芪总皂苷浸膏(I)。
以黄芪甲苷为对照品，采用人光光度法测定浸膏(I)中总皂苷含量，总皂苷含量≥50％。
2、总丹参酮的制备
丹参药材经粉碎后用90～95％的乙醇回流提取两次，第一次8倍量，回流1～2小时，第二次6倍量回流1～2小时，合并两次滤液，减压蒸馏，回收乙醇，用D101大孔吸附树脂吸附分离，经洗脱、浓缩得到主要含总丹参酮浸膏(II)。
以丹参酮IIA为对照品，用分光光度法测定浸膏(II)中总丹参酮的含量，总丹参酮含量≥50％。
3、在实施例2中，经乙醇提取后的丹参滤渣脱尽乙醇，继续用水提取两次，每次8倍量水，回流或煎煮1.5～2.5小时，合并两次滤液，减压脱水浓缩，用D101大孔吸附树脂吸附分离，经洗脱、浓缩得到主要含总酚酸浸膏(III)。
以原儿茶醛为对照品，用分光光度法测定浸膏(III)中总酚酸的含量，总酚酸含量≥50％。
4、颗粒剂的制备
取浸膏(I)0.5份，浸膏(II)3份，浸膏(III)20份，按颗粒剂制备工艺制备颗粒剂。
5、片剂的制备
取浸膏(I)4份，浸膏(II)7份，浸膏(III)50份，按片剂制备工艺制备片剂。
6、胶囊的制备
取浸膏(I)3份，浸膏(II)5份，浸膏(III)30份，按胶囊剂制备工艺制备胶囊。
7、软胶囊的制备
取浸膏(I)2份，浸膏(II)3.5份，浸膏(III)25份，按软胶囊制备工艺制备软胶囊。
本制备患者口服剂量，以有效部位组合物计为120～240mg。
Claims (3)
1、一种治疗慢性肝炎的药物，是由黄芪和丹参的粗提物中分离出的有效部位构成的组合物，其特征在于：主要含总酚酸、总丹参酮和黄芪总皂苷的各有效部位有以下质量比：总酚酸∶总丹参酮∶黄芪总皂苷＝15～50∶3～7∶0.5～4，各有效部位中，总酚酸、总丹参酮和黄芪总皂苷的含量均≥50％。
2、根据权利要求1所述的药物，其特征在于：各有效部位优选以下质量比：总酚酸∶总丹参酮∶黄芪总皂苷＝20～45∶4～6∶1～3。
3、根据权利要求1或2所述的药物，其特征在于：各有效部位最佳质量比：总酚酸∶总丹参酮∶黄芪总皂苷＝25∶3.5∶2。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100649992A CN100411642C (zh) | 2004-10-15 | 2004-10-15 | 一种治疗慢性肝炎的药物 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100649992A CN100411642C (zh) | 2004-10-15 | 2004-10-15 | 一种治疗慢性肝炎的药物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1759855A true CN1759855A (zh) | 2006-04-19 |
| CN100411642C CN100411642C (zh) | 2008-08-20 |
Family
ID=36706162
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004100649992A Expired - Fee Related CN100411642C (zh) | 2004-10-15 | 2004-10-15 | 一种治疗慢性肝炎的药物 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100411642C (zh) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013102437A1 (zh) * | 2012-01-04 | 2013-07-11 | 天士力制药集团股份有限公司 | 丹参或丹参制剂在制备治疗肝纤维化相关疾病的药物中的应用 |
| WO2015027929A1 (zh) * | 2013-08-29 | 2015-03-05 | 天士力制药集团股份有限公司 | 一种中药组合物 |
| US10626077B2 (en) | 2013-08-29 | 2020-04-21 | Tasly Pharmaceutical Group Co., Ltd. | Salvianolic acid compound T, preparation method therefor, and use thereof |
| US11013694B2 (en) | 2013-07-11 | 2021-05-25 | Tasly Pharmaceutical Group Co., Ltd. | Formulation of a micro drop pill and the preparation method thereof |
| USRE49035E1 (en) | 2013-07-11 | 2022-04-19 | Tasly Pharmaceutical Group Co., Ltd. | Traditional Chinese medicine composition, and preparation and application thereof |
| USRE49050E1 (en) | 2013-07-11 | 2022-04-26 | Tasly Pharmaceutical Group Co., Ltd. | Traditional Chinese medicine composition, and preparation and application thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1466947A (zh) * | 2003-05-27 | 2004-01-14 | 杨喜鸿 | 一种含拉米夫定的组合用药物 |
-
2004
- 2004-10-15 CN CNB2004100649992A patent/CN100411642C/zh not_active Expired - Fee Related
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013102437A1 (zh) * | 2012-01-04 | 2013-07-11 | 天士力制药集团股份有限公司 | 丹参或丹参制剂在制备治疗肝纤维化相关疾病的药物中的应用 |
| JP2015503572A (ja) * | 2012-01-04 | 2015-02-02 | タスリー・ファーマシューティカル・グループ・カンパニー・リミテッドＴａｓｌｙ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｇｒｏｕｐ Ｃｏ．， Ｌｔｄ． | 肝線維症に関連する疾患の治療用薬剤の調製におけるラディックス・サルビアエ・ミルチオルヒザエ（タンジン）又はその製剤の使用 |
| AU2013207295B2 (en) * | 2012-01-04 | 2017-10-19 | Tasly Pharmaceutical Group Co., Ltd. | Use of radix salviae miltiorrhizae (danshen) or its preparations in preparation of drugs for treating diseases related to hepatic fibrosis |
| US9895405B2 (en) | 2012-01-04 | 2018-02-20 | Tasly Pharmaceutical Group Co., Ltd. | Use of radix salviae miltiorrhizae (danshen) or its preparations in preparation of drugs for treating diseases related to hepatic fibrosis |
| US11013694B2 (en) | 2013-07-11 | 2021-05-25 | Tasly Pharmaceutical Group Co., Ltd. | Formulation of a micro drop pill and the preparation method thereof |
| USRE49035E1 (en) | 2013-07-11 | 2022-04-19 | Tasly Pharmaceutical Group Co., Ltd. | Traditional Chinese medicine composition, and preparation and application thereof |
| USRE49050E1 (en) | 2013-07-11 | 2022-04-26 | Tasly Pharmaceutical Group Co., Ltd. | Traditional Chinese medicine composition, and preparation and application thereof |
| WO2015027929A1 (zh) * | 2013-08-29 | 2015-03-05 | 天士力制药集团股份有限公司 | 一种中药组合物 |
| CN104415045A (zh) * | 2013-08-29 | 2015-03-18 | 天士力制药集团股份有限公司 | 一种药物组合物 |
| CN104415045B (zh) * | 2013-08-29 | 2019-03-22 | 天士力医药集团股份有限公司 | 一种药物组合物 |
| US10300030B2 (en) | 2013-08-29 | 2019-05-28 | Tasly Pharmaceutical Group Co., Ltd. | Traditional Chinese medicine composition |
| US10626077B2 (en) | 2013-08-29 | 2020-04-21 | Tasly Pharmaceutical Group Co., Ltd. | Salvianolic acid compound T, preparation method therefor, and use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100411642C (zh) | 2008-08-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110893197B (zh) | 用于治疗痛风的蔓三七提取物及其制备方法 | |
| CN101721488B (zh) | 一种治疗肝病的药物组合物及其制备方法 | |
| CN103386022B (zh) | 一种治疗结核性胸膜炎的中药组合物 | |
| CN102784248B (zh) | 一种防治酒精性肝损伤的中药组合物 | |
| CN100411642C (zh) | 一种治疗慢性肝炎的药物 | |
| CN1274356C (zh) | 治疗乙肝后肝纤维化和肝硬化的中药组合物及其制造方法 | |
| CN1245173C (zh) | 一种治疗肝纤维化和肝硬化的药物组合物及其制备方法 | |
| CN1283288C (zh) | 一种降脂组合物及其制备方法 | |
| KR20120022134A (ko) | 한약재를 이용한 피로 회복 식품 | |
| CN102430025A (zh) | 一种治疗盆腔炎的药物组合物及其制备方法 | |
| CN101411743B (zh) | 中药玉屏风散在制备防治肝损伤药物中的应用 | |
| CN100415255C (zh) | 一种中药组合物及其制备方法 | |
| CN1087617C (zh) | 一种治疗肝炎的胶囊 | |
| CN100336537C (zh) | 一种抗疲劳增强免疫力的中药组合物及其制备方法 | |
| CN112402566B (zh) | 一种中药组合物在制备治疗膝关节滑膜炎的药物中的用途 | |
| CN101632829B (zh) | 一种抗肝纤维化的中药组合物及其制备方法与药物制剂 | |
| CN103977154A (zh) | 一种用于保肝护肝的药物组合物 | |
| CN111228388A (zh) | 一种治疗肝病的药物组合物及其使用方法 | |
| CN111494508B (zh) | 一种中药痛风贴的制备方法及其产品 | |
| CN120459181B (zh) | 一种复方风湿宁胶囊、制备方法及其应用 | |
| CN115040594B (zh) | 一种治疗带状疱疹的中药组合物 | |
| CN1470271A (zh) | 一种治疗肝纤维化疾病的中药复方制剂及其制备方法 | |
| CN1544068A (zh) | 一种抗痛风药物组合物及其制备方法 | |
| CN102058825A (zh) | 一种治疗肝炎的中药组合物及其制备方法 | |
| CN1310669C (zh) | 一种治疗慢性肝炎的药物组合物及其制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: ANHUI HEALSTAR PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: HEFEI HENGXING INSTITUTE OF MATERIA MEDICA Effective date: 20120615 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 230088 HEFEI, ANHUI PROVINCE TO: 230051 HEFEI, ANHUI PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20120615 Address after: Five road 230051 Anhui city in Hefei Province, Baohe Industrial District No. 15 weft Patentee after: Anhui Heal Star Pharmaceutical Co.,Ltd. Address before: 230088 biological medicine garden, high tech Zone, Anhui, Hefei Patentee before: Hefei Hengxing Institute of Materia Medica |
|
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20080820 Termination date: 20141015 |
|
| EXPY | Termination of patent right or utility model |