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US20090117209A1 - Andrographis paniculata extract - Google Patents

Andrographis paniculata extract Download PDF

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Publication number
US20090117209A1
US20090117209A1 US11/934,143 US93414307A US2009117209A1 US 20090117209 A1 US20090117209 A1 US 20090117209A1 US 93414307 A US93414307 A US 93414307A US 2009117209 A1 US2009117209 A1 US 2009117209A1
Authority
US
United States
Prior art keywords
extract
andrographolide
dry weight
constitute
deoxyandrographolide
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.)
Abandoned
Application number
US11/934,143
Other languages
English (en)
Inventor
Jifeng Duan
Zhiming Ma
Xiaoqiang Yan
Weihan Zhang
Tao Wang
Yu Cai
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nutrition Science Partners Ltd
Original Assignee
Hutchison Medipharma Enterprises Ltd
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 Ltd filed Critical Hutchison Medipharma Enterprises Ltd
Priority to US11/934,143 priority Critical patent/US20090117209A1/en
Assigned to HUTCHINSON MEDIPHARMA ENTERPRISES LIMITED reassignment HUTCHINSON MEDIPHARMA ENTERPRISES LIMITED ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: YAN, XIOAQIANG, MA, ZHIMING, CAI, YU, DUAN, JIFENG, WANG, TAO, ZHANG, WEIHAN
Assigned to HUTCHISON MEDIPHARMA ENTERPRISES LIMITED reassignment HUTCHISON MEDIPHARMA ENTERPRISES LIMITED CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE NAME PREVIOUSLY RECORDED ON REEL 020150 FRAME 0556. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Assignors: YAN, XIOQIANG, MA, ZHIMING, CAI, YU, DUAN, JIFENG, WANG, TAO, ZHANG, WEIHAN
Priority to TW097125255A priority patent/TWI536997B/zh
Priority to KR20157002001A priority patent/KR20150021126A/ko
Priority to RU2010122317/15A priority patent/RU2468809C2/ru
Priority to JP2010532287A priority patent/JP2011502995A/ja
Priority to PCT/US2008/082022 priority patent/WO2009059158A1/en
Priority to KR1020107011798A priority patent/KR101545366B1/ko
Priority to CA2704773A priority patent/CA2704773A1/en
Priority to MX2010004773A priority patent/MX2010004773A/es
Priority to AU2008318487A priority patent/AU2008318487B2/en
Priority to BRPI0817138A priority patent/BRPI0817138A2/pt
Priority to EP08845832A priority patent/EP2217254A4/en
Priority to US12/264,646 priority patent/US8557302B2/en
Publication of US20090117209A1 publication Critical patent/US20090117209A1/en
Priority to US13/609,318 priority patent/US8557308B2/en
Assigned to NUTRITION SCIENCE PARTNERS LIMITED reassignment NUTRITION SCIENCE PARTNERS LIMITED ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: HUTCHISON MEDIPHARMA ENTERPRISES LIMITED
Priority to US14/019,613 priority patent/US20140004212A1/en
Priority to US14/321,394 priority patent/US20140315846A1/en
Priority to PH12014501926A priority patent/PH12014501926A1/en
Priority to JP2014227140A priority patent/JP2015025024A/ja
Priority to US14/990,749 priority patent/US20160193268A1/en
Abandoned legal-status Critical Current

Links

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.
  • Crohn's disease 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.
  • ulcerative colitis and Crohn's disease are attributed to dysregulation of pro-inflammatory cytokine, including TNF ⁇ and IL-1 ⁇ .
  • pro-inflammatory cytokine including TNF ⁇ and IL-1 ⁇ .
  • Therapeutic agents have been developed based on down-regulation of pro-inflammatory cytokine.
  • 5-aminosalicylic acid an inhibitor of TNF ⁇ signaling events, has been used to treat ulcerative colitis.
  • Therapeutic Immunology Ed. Austen, K F., Blackwell Publishing, 2001, 159-167 has limited efficacy or significant side effects.
  • 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, polysacchlorides, 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.
  • compositions containing the extract described above and a pharmaceutically acceptable carrier are also within the scope of this invention.
  • a pharmaceutical composition containing the extract described above and a pharmaceutically acceptable carrier 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.
  • parenteral 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.
  • 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
  • a sterile injectable composition can be formulated according to techniques known in the art using suitable dispersing or wetting agents (such as, for example, Tween 80) and suspending agents.
  • the sterile injectable preparation can also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol.
  • suitable 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.
  • 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 C12).
  • 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. Pat. Nos. 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-1 ⁇ .
  • 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.
  • Dextrin was added (0.03 kg) to the wet mixture, which was then spray-dried (inlet: 185-195° C.; outlet: 90-100° 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° 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 (221.0 g), silicon dioxide (2.125 g), and microcrystalline cellulous (34.0 g) were mixed. The mixture was filled into #0 hard-shell capsules using a capsule filling board to form the desired Andrographis paniculata extract-containing capsules (351.25 mg the mixture/capsule, eqv. to 200 mg the extract/capsule).
  • 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° 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° C. under 5% CO 2 overnight.
  • TNF ⁇ and IL-1 ⁇ are measured using the TNF ⁇ ELISA (Enzyme Linked Immunosorbent Assay) Kit and IL1- ⁇ ELISA Kit (Jingmei Bioengineer Technology).
  • the inhibition ratio is calculated as follows:
  • C extract is the concentration of TNF ⁇ or IL-1 ⁇ in PBMC cells treated with the extract and LPS
  • C LPS is the concentration of TNF ⁇ or IL-1 ⁇ in PBMC cells treated with LPS and dexamethason
  • C Control is the concentration of TNF ⁇ or IL-1 ⁇ in PBMC cells without being treated with LPS or the extract.
  • 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.
  • PMS partial Mayo scores
  • biopsies taken during colonoscopy were graded histologically with a scale of 0-3.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Mycology (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Medical Informatics (AREA)
  • Microbiology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Molecular Biology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Medicinal Preparation (AREA)
  • Furan Compounds (AREA)
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US11/934,143 2007-11-02 2007-11-02 Andrographis paniculata extract Abandoned US20090117209A1 (en)

Priority Applications (19)

Application Number Priority Date Filing Date Title
US11/934,143 US20090117209A1 (en) 2007-11-02 2007-11-02 Andrographis paniculata extract
TW097125255A TWI536997B (zh) 2007-11-02 2008-07-04 穿心蓮萃取物
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
EP08845832A EP2217254A4 (en) 2007-11-02 2008-10-31 EXTRACT FROM ANDROGRAPHIS PANICULATA
MX2010004773A MX2010004773A (es) 2007-11-02 2008-10-31 Extracto de andrographis paniculata.
AU2008318487A AU2008318487B2 (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)
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
PCT/US2008/082022 WO2009059158A1 (en) 2007-11-02 2008-10-31 Andrographis paniculata extract
KR1020107011798A KR101545366B1 (ko) 2007-11-02 2008-10-31 천심련 추출물
CA2704773A CA2704773A1 (en) 2007-11-02 2008-10-31 Andrographis paniculata extract
KR20157002001A KR20150021126A (ko) 2007-11-02 2008-10-31 천심련 추출물
US12/264,646 US8557302B2 (en) 2007-11-02 2008-11-04 Andrographis paniculata extract
US13/609,318 US8557308B2 (en) 2007-11-02 2012-09-11 Andrographis paniculata extract
US14/019,613 US20140004212A1 (en) 2007-11-02 2013-09-06 Andrographis paniculata extract
US14/321,394 US20140315846A1 (en) 2007-11-02 2014-07-01 Andrographis paniculata extract
PH12014501926A PH12014501926A1 (en) 2007-11-02 2014-08-27 Andrographis paniculata extract
JP2014227140A JP2015025024A (ja) 2007-11-02 2014-11-07 アンドログラフィス・パニキュラータ抽出物及び同抽出物を含む製薬組成物並びに同抽出物の製薬組成物の製造における使用
US14/990,749 US20160193268A1 (en) 2007-11-02 2016-01-07 Andrographis paniculata extract

Applications Claiming Priority (1)

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

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US12/264,646 Division US8557302B2 (en) 2007-11-02 2008-11-04 Andrographis paniculata extract
US13/609,318 Continuation US8557308B2 (en) 2007-11-02 2012-09-11 Andrographis paniculata extract

Publications (1)

Publication Number Publication Date
US20090117209A1 true US20090117209A1 (en) 2009-05-07

Family

ID=40588302

Family Applications (6)

Application Number Title Priority Date Filing Date
US11/934,143 Abandoned US20090117209A1 (en) 2007-11-02 2007-11-02 Andrographis paniculata extract
US12/264,646 Active 2029-07-12 US8557302B2 (en) 2007-11-02 2008-11-04 Andrographis paniculata extract
US13/609,318 Active US8557308B2 (en) 2007-11-02 2012-09-11 Andrographis paniculata extract
US14/019,613 Abandoned US20140004212A1 (en) 2007-11-02 2013-09-06 Andrographis paniculata extract
US14/321,394 Abandoned US20140315846A1 (en) 2007-11-02 2014-07-01 Andrographis paniculata extract
US14/990,749 Abandoned US20160193268A1 (en) 2007-11-02 2016-01-07 Andrographis paniculata extract

Family Applications After (5)

Application Number Title Priority Date Filing Date
US12/264,646 Active 2029-07-12 US8557302B2 (en) 2007-11-02 2008-11-04 Andrographis paniculata extract
US13/609,318 Active US8557308B2 (en) 2007-11-02 2012-09-11 Andrographis paniculata extract
US14/019,613 Abandoned US20140004212A1 (en) 2007-11-02 2013-09-06 Andrographis paniculata extract
US14/321,394 Abandoned US20140315846A1 (en) 2007-11-02 2014-07-01 Andrographis paniculata extract
US14/990,749 Abandoned US20160193268A1 (en) 2007-11-02 2016-01-07 Andrographis paniculata extract

Country Status (12)

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

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070202164A1 (en) * 2006-02-28 2007-08-30 Hutchison Medipharma Enterprises Limited Andrographis Extract Formulations
US20090117210A1 (en) * 2007-11-02 2009-05-07 Hutchison Medipharma Enterprises Limited Andrographis paniculata extract
USRE42718E1 (en) 2004-04-28 2011-09-20 Hutchison Medipharma Enterprises Limited Crude extracts from andrographis paniculata
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