WO2009059158A1 - Andrographis paniculata extract - Google Patents

Andrographis paniculata extract Download PDF

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Publication number
WO2009059158A1
WO2009059158A1 PCT/US2008/082022 US2008082022W WO2009059158A1 WO 2009059158 A1 WO2009059158 A1 WO 2009059158A1 US 2008082022 W US2008082022 W US 2008082022W WO 2009059158 A1 WO2009059158 A1 WO 2009059158A1
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WO
WIPO (PCT)
Prior art keywords
extract
andrographolide
dry weight
constitute
deoxyandrographolide
Prior art date
Application number
PCT/US2008/082022
Other languages
English (en)
French (fr)
Inventor
Jifeng Duan
Zhiming Ma
Xiaoquiang Yan
Weihan Zhang
Tao Wang
Yu Cai
Original Assignee
Hutchison Medipharma Enterprises Limited
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Hutchison Medipharma Enterprises Limited filed Critical Hutchison Medipharma Enterprises Limited
Priority to EP08845832A priority Critical patent/EP2217254A4/en
Priority to CA2704773A priority patent/CA2704773A1/en
Priority to RU2010122317/15A priority patent/RU2468809C2/ru
Priority to KR20157002001A priority patent/KR20150021126A/ko
Priority to JP2010532287A priority patent/JP2011502995A/ja
Priority to AU2008318487A priority patent/AU2008318487B2/en
Priority to BRPI0817138A priority patent/BRPI0817138A2/pt
Priority to MX2010004773A priority patent/MX2010004773A/es
Publication of WO2009059158A1 publication Critical patent/WO2009059158A1/en
Priority to PH12014501926A priority patent/PH12014501926A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/19—Acanthaceae (Acanthus family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • Inflammatory bowel disease includes chronic gastrointestinal disorders characterized by infiltration of inflammatory cells into the mucosa of the digestive tract. Ulcerative colitis and Crohn's disease are two prevalent conditions among them. Ulcerative colitis takes place in the large intestine (i.e., colon). The inner lining of the disordered intestine becomes inflamed and develops ulcers.
  • ulcerative colitis most commonly affects the end of the small intestine (i.e., terminal ileum) and parts of the large intestine. It causes inflammation that extends much deeper into the layers of the intestinal wall than ulcerative colitis. Both ulcerative colitis and Crohn's disease are attributed to dysregulation of pro-inflammatory cytokine, including TNF ⁇ and IL-l ⁇ . See, e.g., McClane S. J. et al., Journal of Parenteral and Enteral Nutrition 23, 1999. Therapeutic agents have been developed based on down-regulation of pro-inflammatory cytokine. For example, 5 -aminosalicylic acid, an inhibitor of TNF ⁇ signaling events, has been used to treat ulcerative colitis. See, e.g., Therapeutic Immunology Ed. Austen, K F.,
  • This invention is based on a surprising finding that an extract of Andrographis paniculata effectively exerts a curative effect against inflammatory bowel disease.
  • the extract contains andrographolide lactones, polysacchorides, and flavanoids; constituting 10-22% (preferably 13-17%), 18-28% (preferably 20-25%), and 10-15% (preferably 12-14%) of the dry weight of the extract, respectively.
  • the andrographolide lactones include andrographolide, 14-deoxyandrographolide, 14- deoxy-11,12-dehydroandrographolide, and neoandrographolide, which constitute 2- 20% (preferably 3-10%, more preferably 6-10%), 0.01-6% (preferably 0.01-2%, more preferably 0.01-1%), 1-6% (preferably 2-5%, more preferably 2-4%), and 1-5% (preferably 2-4%) of the dry weight of the extract, respectively.
  • Another aspect of this invention relates to a method of treating inflammatory bowel disease (including Crohn's disease and ulcerative colitis).
  • the method includes administering to a subject in need of the treatment an effective amount of the above- described extract.
  • a pharmaceutical composition containing the extract described above and a pharmaceutically acceptable carrier are also within the scope of this invention, the use of such a composition to treat inflammatory bowel disease, and the use of such a composition for the manufacture of a medicament for treating this disease.
  • the extract of this invention can immerse the aerial part of Andrographis paniculata in 80-95% ethanol, collect the ethanol phase, and then remove the ethanol.
  • An actual example is provided below.
  • the extract thus obtained can be further purified by thin layer chromatography, flash column chromatography, high performance liquid chromatography, or any other suitable methods.
  • This invention includes methods of treating inflammatory bowel disease by administering to a subject in need thereof an effective amount of the extract of this invention.
  • an effective amount refers to the amount of the extract which is required to confer one of the above-described therapeutic effects in the subject. Effective amounts may vary, as recognized by those skilled in the art, depending on route of administration, excipient usage, and the possibility of co-usage with other agents. Preferably, the effective amount is 1-100 mg/kg/day based on the dry weight of the extract.
  • treating refers to administering the extract to a subject that has inflammatory bowel disease, or has a symptom of the disease, or has a predisposition toward the disease, with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve, or affect the disease, the symptoms of the disease, or the predisposition toward the disease.
  • compositions that is either the above-mentioned extract alone or a mixture of the extract and a pharmaceutically acceptable carrier.
  • parenteral as used herein includes subcutaneous, intracutaneous, intravenous, intramuscular, intraarticular, intraarterial, intrasynovial, intrasternal, intrathecal, intralesional and intracranial injection or infusion techniques.
  • An oral composition can be any orally acceptable dosage form including, but not limited to, tablets, capsules, emulsions and aqueous suspensions, dispersions and solutions.
  • Commonly used carriers for tablets include lactose and corn starch.
  • Lubricating agents such as magnesium stearate, are also typically added to tablets. Tablets may also be coated for delivery or cosmetic effects.
  • useful diluents include lactose and dried corn starch.
  • the active ingredient can be suspended or dissolved in an oily phase combined with emulsifying or suspending agents. If desired, certain sweetening, flavoring, or coloring agents can be added.
  • a rectal composition can be any rectally acceptable dosage form including, but not limited to, cream, gel, emulsion, suspension, suppository, and tablet.
  • One preferred dosage form is a suppository having a shape and size designed for introduction into the rectal orifice of the human body.
  • a suppository usually softens, melts, or dissolves at body temperature.
  • Suppository excipients include, but are not limited to, theobroma oil (cocoa butter), glycerinated gelatin, hydrogenated vegetable ails, mixtures of polyethylene glycols of various molecular weights, and fatty acid esters of polyethylene glycol.
  • a sterile injectable composition e.g., aqueous or oleaginous suspension
  • suitable dispersing or wetting agents such as, for example, Tween 80
  • the sterile injectable preparation can also be a sterile injectable solution or suspension in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3- butanediol.
  • acceptable vehicles and solvents that can be employed are mannitol, water, Ringer's solution and isotonic sodium chloride solution.
  • sterile, fixed oils are conventionally employed as a solvent or suspending medium (e.g., synthetic mono- or di-glycerides).
  • Fatty acids such as oleic acid and its glyceride derivatives are useful in the preparation of injectables, as are natural pharmaceutically-acceptable oils, such as olive oil or castor oil, especially in their polyoxyethylated versions.
  • oils such as olive oil or castor oil, especially in their polyoxyethylated versions.
  • These oil solutions or suspensions can also contain a long-chain alcohol diluent or dispersant, or carboxymethyl cellulose or similar dispersing agents.
  • An inhalation composition can be prepared according to techniques well known in the art of pharmaceutical formulation and can be prepared as solutions in saline, employing benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, fluorocarbons, and/or other solubilizing or dispersing agents known in the art.
  • a topical composition can be formulated in form of oil, cream, lotion, ointment and the like.
  • suitable carriers for the composition include vegetable or mineral oils, white petrolatum (white soft paraffin), branched chain fats or oils, animal fats and high molecular weight alcohols (greater than C 12).
  • the preferred carriers are those in which the active ingredient is soluble.
  • Emulsifiers, stabilizers, humectants and antioxidants may also be included as well as agents imparting color or fragrance, if desired.
  • transdermal penetration enhancers may be employed in these topical formulations. Examples of such enhancers can be found in U.S. Patents 3,989,816 and 4,444,762.
  • Creams are preferably formulated from a mixture of mineral oil, self-emulsifying beeswax and water in which mixture the active ingredient, dissolved in a small amount of an oil, such as almond oil, is admixed.
  • An example of such a cream is one which includes about 40 parts water, about 20 parts beeswax, about 40 parts mineral oil and about 1 part almond oil.
  • Ointments may be formulated by mixing a solution of the active ingredient in a vegetable oil, such as almond oil, with warm soft paraffin and allowing the mixture to cool.
  • An example of such an ointment is one which includes about 30% almond and about 70% white soft paraffin by weight.
  • a carrier in a pharmaceutical composition must be "acceptable” in the sense of being compatible with the active ingredient of the formulation (and preferably, capable of stabilizing it) and not deleterious to the subject to be treated.
  • solubilizing agents such as cyclodextrins (which form specific, more soluble complexes with one or more of active compounds of the extract), can be utilized as pharmaceutical excipients for delivery of the active compounds.
  • examples of other carriers include colloidal silicon dioxide, magnesium stearate, cellulose, sodium lauryl sulfate, and D&C Yellow # 10.
  • a suitable in vitro assay can be used to preliminarily evaluate the efficacy of the above-described extract in inhibiting expression of TNF ⁇ or IL-I ⁇ .
  • the extract can further be examined for its efficacy in treating inflammatory bowel disease by in vivo assays.
  • the extract can be administered to an animal (e.g., a mouse model) or human having inflammatory bowel disease and its therapeutic effects are then accessed. Based on the results, an appropriate dosage range and administration route can also be determined.
  • Example 1 Preparation of the Andrographis panicula ta extract
  • Dextrin was added (0.03 kg) to the wet mixture, which was then spray-dried (inlet: 185-195°C; outlet: 90-100 0 C).
  • the solid extract thus obtained was ground, sieved, and packaged to form tablets and capsules as described below.
  • Tablets were prepared as follows. Starch (10 g) and sugar (10 g) were mixed with purified water (80.0 g) to yield a paste. Separately, the extract (500.0 g), starch (140.0 g), microcrystalline cellulous (337.5 g), and the paste were mixed, wet granulized, and dried at 55 0 C. The dried granules (957.6 g) and magnesium stearate (2.4 g) were mixed for 5 minutes.
  • the final mixture was compressed to form tablets (400 mg/tablet, eqv. to 200 mg the extract/tablet).
  • the tablets were film-coated with a paste prepared by mixing hypromellose (7.5 g), propylene glycol (1.6 g), titanium dioxide (3.0 g), Food Drug & Cosmetic color lake (0.4 g), and purified water (87.5 g) to afford the desired Andrographis paniculata extract-containing tablets.
  • Capsules were prepared as follows. The extract (340.0 g), pre-dried starch
  • PBMC Peripheral blood monocytes
  • 10 ⁇ l of the extract of Andrographis paniculata in DMSO is added into each well (final concentrations: 0.1, 0.3, 1, 3, 10, and 30 ⁇ g/ml).
  • Dexamethason final concentration: 10 ⁇ M
  • 10 ⁇ l of the media is used as a negative control.
  • the plate is incubated at 37 0 C under 5% CO 2 for 15 minutes. After 10 ⁇ l aliquots of 100 ⁇ g/ml lipopolysaccharide are added to all wells except for the negative controls, the plate is incubated at 37 0 C under 5% CO 2 overnight.
  • TNF ⁇ and IL- l ⁇ are measured using the TNF ⁇ ELISA (Enzyme Linked Immunosorbent Assay) Kit and ILl- ⁇ ELISA Kit (Jingmei Bioengineer Technology).
  • the inhibition ratio is calculated as follows: ⁇ -extract " ⁇ -Control
  • C ex tract is the concentration of TNF ⁇ or IL-I ⁇ in PBMC cells treated with the extract and LPS
  • C LPS is the concentration of TNF ⁇ or IL- l ⁇ in PBMC cells treated with LPS and dexamethason
  • Ccontrol is the concentration of TNF ⁇ or IL- l ⁇ in PBMC cells without being treated with LPS or the extract.
  • Example 3 Treatment of Inflammatory Bowel Disease in Mouse Model
  • Balb/c male mice (18-24 g, purchased from Chinese Academy of Science animal center) are anaesthetized with 1% pentobarbital sodium at 0.05 mg/10 g. 1.5 mg of 2,4,6-trinitrobenzenesulfonic acid in 50% ethanol is administered slowly to each mouse (except blank control mice) via a catheter to induce inflammatory bowel disease.
  • Blank control mice only receive 0.1 ml of 50% ethanol.
  • the mice are treated with the test sample 24 hours and 2 hours prior to the inflammatory bowel disease administration and daily for 5 days after the administration.
  • mice The body weight of each mouse is monitored every day before and after the 2,4,6-trinitrobenzenesulfonic acid administration.
  • the mice are sacrificed 24 hours after the last administration of test samples. Colons are removed and weighed. Furthermore, the colon weight to body weight ratio is calculated and adhesion between colon and other organs is also monitored.
  • Samples of colon tissues located precisely 2 cm above the anal canal are obtained, fixed in 10% buffered phosphate, embedded in paraffin, sectioned, and stained with hematoxylin/eosin.
  • the degree of inflammation on microscopic cross sections is graded from 0 to 4 (0: no signs of inflammation; 1 : a very low level of inflammation; 2: a low level of leukocyte infiltration; 3: a high level of leukocyte infiltration, a high vascular density, and a thickened colon wall; and 4: transmural infiltrations, loss of goblet cells, a high vascular density, and a thickened colon wall).
  • the therapeutic effects were assessed biweekly using a scale similar to the partial Mayo Scoring System, and the clinical symptom score reduction (>50% reduction in symptoms) was calculated. Scores were then retrospectively calculated using the standard partial Mayo scores (PMS), clinical response (improvement >2 points or final score of 0) and remission ( ⁇ 1 PMS score at week 8). Colonoscopies at the beginning and at the end of treatment were rated with a modified Baron score, and biopsies taken during colonoscopy were graded histologically with a scale of 0-3. Patients in the two groups had similar demographics. In each group, the mean duration of disease ranged from 3.5-3.7 years and the baseline mean PMS was 3.8.
  • the clinical symptom score reduction was 27% in the patients at week 2 and improved to 56% in the patients by week 8.
  • the 55 intent-to-treat Etiasa treated patients showed similar reduction.
  • the clinical response rate at week 8 was 58% in the patients treated with the extract and 58% in the patients treated with Etiasa.
  • the remission rate at week 8 was 43% in the patients treated with the extract and 58% in the patients treated with Etiasa.
  • the results of PMS at the baseline and week 8 in both groups are statistically significant (p ⁇ 0.0002). Endoscopically, at week 8, 28% of the patients treated with the extract and

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PCT/US2008/082022 2007-11-02 2008-10-31 Andrographis paniculata extract WO2009059158A1 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
EP08845832A EP2217254A4 (en) 2007-11-02 2008-10-31 EXTRACT FROM ANDROGRAPHIS PANICULATA
CA2704773A CA2704773A1 (en) 2007-11-02 2008-10-31 Andrographis paniculata extract
RU2010122317/15A RU2468809C2 (ru) 2007-11-02 2008-10-31 Экстракт андрографиса метельчатого (andrographis paniculata)
KR20157002001A KR20150021126A (ko) 2007-11-02 2008-10-31 천심련 추출물
JP2010532287A JP2011502995A (ja) 2007-11-02 2008-10-31 アンドログラフィス・パニキュラータ抽出物
AU2008318487A AU2008318487B2 (en) 2007-11-02 2008-10-31 Andrographis paniculata extract
BRPI0817138A BRPI0817138A2 (pt) 2007-11-02 2008-10-31 extrato de andrographis paniculata, extrato preparado a partir de andrographis paniculata, composição farmacêutica e método de tratamento de uma doença inflamatória do intestino em um indivíduo com necessidade do mesmo
MX2010004773A MX2010004773A (es) 2007-11-02 2008-10-31 Extracto de andrographis paniculata.
PH12014501926A PH12014501926A1 (en) 2007-11-02 2014-08-27 Andrographis paniculata extract

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US11/934,143 US20090117209A1 (en) 2007-11-02 2007-11-02 Andrographis paniculata extract
US11/934,143 2007-11-02

Publications (1)

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WO2009059158A1 true WO2009059158A1 (en) 2009-05-07

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Application Number Title Priority Date Filing Date
PCT/US2008/082022 WO2009059158A1 (en) 2007-11-02 2008-10-31 Andrographis paniculata extract

Country Status (12)

Country Link
US (6) US20090117209A1 (pt-pt)
EP (1) EP2217254A4 (pt-pt)
JP (2) JP2011502995A (pt-pt)
KR (2) KR101545366B1 (pt-pt)
AU (1) AU2008318487B2 (pt-pt)
BR (1) BRPI0817138A2 (pt-pt)
CA (1) CA2704773A1 (pt-pt)
MX (1) MX2010004773A (pt-pt)
PH (1) PH12014501926A1 (pt-pt)
RU (1) RU2468809C2 (pt-pt)
TW (1) TWI536997B (pt-pt)
WO (1) WO2009059158A1 (pt-pt)

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USRE42718E1 (en) 2004-04-28 2011-09-20 Hutchison Medipharma Enterprises Limited Crude extracts from andrographis paniculata
CN102382083A (zh) * 2010-09-01 2012-03-21 天津天士力现代中药资源有限公司 一种穿心莲内酯的制备方法
CN102885775A (zh) * 2011-07-19 2013-01-23 重庆莱美药业股份有限公司 一种炎琥宁无菌粉及其制备方法
CN103145658A (zh) * 2012-04-12 2013-06-12 江西青峰药业有限公司 17-氢-9-去氢穿心莲内酯-3-硫酸酯钠(或钾)、17-氢-9-去氢穿心莲内酯-19-硫酸酯钠(或钾)、17-氢-9-去氢穿心莲内酯-3,19-二硫酸酯钠(或钾)组合物的一次制备方法及其制备药物用途
US8557302B2 (en) 2007-11-02 2013-10-15 Nutrition Science Partners Limited Andrographis paniculata extract
CN103961444A (zh) * 2014-05-17 2014-08-06 董云 一种治疗下肢丹毒的中药外敷剂
CN104311515A (zh) * 2014-09-04 2015-01-28 桂林甙元生物科技有限公司 穿心莲内酯和脱水穿心莲内酯的分离提取工艺
CN104920517A (zh) * 2015-05-21 2015-09-23 北京联合大学 一种防治果树褐腐病的穿心莲水剂及其制备方法
CN105153082A (zh) * 2015-09-30 2015-12-16 成都中医药大学 穿心莲内酯的大生产工艺
CN105884722A (zh) * 2016-04-27 2016-08-24 聊城大学 一种从穿心莲中分离纯化穿心莲内酯和脱水穿心莲内酯的方法
WO2018082568A1 (en) 2016-11-02 2018-05-11 Nutrition Science Partners Limited Extracts of andrographis paniculata, methods for preparation and use thereof
CN115487177A (zh) * 2022-08-15 2022-12-20 四川大学华西医院 一种黄酮类化合物用于治疗溃疡性结肠炎的新用途

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US20070202164A1 (en) * 2006-02-28 2007-08-30 Hutchison Medipharma Enterprises Limited Andrographis Extract Formulations
CN102226791A (zh) * 2011-03-31 2011-10-26 宁波双伟制药有限公司 高效液相色谱法测定感冒清胶囊中脱水穿心莲内酯含量的方法
CN102558257B (zh) * 2011-12-23 2014-06-18 柳州市绿翔生物技术有限公司 新穿心莲内酯的分离纯化方法
CN102809625B (zh) * 2012-08-23 2015-02-04 神威药业集团有限公司 一种穿心莲内酯有关物质的测定方法
JP6166926B2 (ja) * 2013-03-26 2017-07-19 山洋電気株式会社 リニアモータ
CN103265509B (zh) * 2013-05-28 2016-01-20 江西中医学院 一种真空度调控辅助提取穿心莲活性成分的方法
EP2819162B1 (en) * 2013-06-24 2020-06-17 IMEC vzw Method for producing contact areas on a semiconductor substrate
RU2681930C2 (ru) * 2013-08-06 2019-03-14 Тасли Фармасьютикал Груп Ко., Лтд. Применение андрографолида в получении фармацевтического препарата для лечения воспалительного заболевания кишечника, микропеллета с андрографолидом для целенаправленной доставки в кишечник и способ ее получения
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CN104920517B (zh) * 2015-05-21 2018-02-06 北京联合大学 一种防治果树褐腐病的穿心莲水剂及其制备方法
CN105153082A (zh) * 2015-09-30 2015-12-16 成都中医药大学 穿心莲内酯的大生产工艺
CN105884722A (zh) * 2016-04-27 2016-08-24 聊城大学 一种从穿心莲中分离纯化穿心莲内酯和脱水穿心莲内酯的方法
CN105884722B (zh) * 2016-04-27 2018-03-13 聊城大学 一种从穿心莲中分离纯化穿心莲内酯和脱水穿心莲内酯的方法
WO2018082568A1 (en) 2016-11-02 2018-05-11 Nutrition Science Partners Limited Extracts of andrographis paniculata, methods for preparation and use thereof
CN110049762A (zh) * 2016-11-02 2019-07-23 营养科学合作伙伴有限公司 穿心莲提取物及其制备方法和用途
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CN115487177A (zh) * 2022-08-15 2022-12-20 四川大学华西医院 一种黄酮类化合物用于治疗溃疡性结肠炎的新用途
CN115487177B (zh) * 2022-08-15 2023-11-24 四川大学华西医院 一种黄酮类化合物用于治疗溃疡性结肠炎的新用途

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