USRE43423E1 - Crude extracts from Andrographis paniculata - Google Patents

Crude extracts from Andrographis paniculata Download PDF

Info

Publication number
USRE43423E1
USRE43423E1 US13/189,444 US201113189444A USRE43423E US RE43423 E1 USRE43423 E1 US RE43423E1 US 201113189444 A US201113189444 A US 201113189444A US RE43423 E USRE43423 E US RE43423E
Authority
US
United States
Prior art keywords
weight
andrographolide
extract
deoxy
dehydrogen
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.)
Active
Application number
US13/189,444
Inventor
Xiaoqiang Yan
Tao Wang
Zhiming Ma
Weihan Zhang
Jifeng Duan
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 US13/189,444 priority Critical patent/USRE43423E1/en
Application granted granted Critical
Publication of USRE43423E1 publication Critical patent/USRE43423E1/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
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/19Acanthaceae (Acanthus family)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365Lactones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/06Antiasthmatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/06Antipsoriatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • A61P31/18Antivirals for RNA viruses for HIV
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/04Immunostimulants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/04Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Definitions

  • Tumor Necrosis Factor alpha a mononuclear cytokine, is predominantly produced by monocytes and macrophages. It possesses various biological activities: (1) killing cancer cells or inhibiting growth of cancer cells, (2) enhancing phagocytosis of neutrophilic granulocyte, (3) killing infectious pathogens, and (4) increasing expression of adhesion molecules on vascular endothelial cells during inflammatory responses.
  • TNF- ⁇ disorders related to expression of TNF- ⁇ include, but are not limited to, rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, spondyloarthropathies, inflammatory bowel disease (including Crohn's disease and ulcerative colitis), chronic heart failure, systemic lupus erythematosus, scleroderma, sarcoidosis, polymyositis/dermatomyositis, psoriasis, multiple myeloma, myelodysplastic syndrome, acute myelogenous leukemia, Parkinson's disease, AIDS dementia complex, Alzheimer's disease, depression, sepsis, pyoderma gangrenosum, hematosepsis, septic shock, Behcet's syndrome, graft-versus-host disease, uveitis, Wegener's granulomatosis, Sjogren's syndrome, chronic obstructive pulmonary disease
  • Interleukin-1 beta IL-1 ⁇
  • IL-1 ⁇ Interleukin-1 beta
  • monocytes hematosepsis
  • monocytes hematosepsis
  • dendritic cells mediates a wide range of immune and inflammatory responses.
  • IL-1 ⁇ Interleukin-1 beta
  • disorders such as rheumatoid arthritis, hematosepsis, periodontal disease, chronic heart failure,
  • This invention is based on a surprising discovery that an extract of Andrographis paniculata inhibits expression of both TNF ⁇ and IL-1 ⁇ .
  • the extract obtained from the aerial part of Andrographis paniculata, contains andrographolide, 14-deoxy-andrographolide, 14-deoxy-11,12-dehydrogen-andrographolide, and neoandrographolide.
  • the extract contains 2-20% by weight andrographolide, 1-6% by weight 14-deoxy-andrographolide, 1-12% by weight 14-deoxy-11,12-dehydrogen-andrographolide, and 1-5% by weight neoandrographolide.
  • the extract contains 3-8% by weight andrographolide, 3-5% by weight 14-deoxy-andrographolide, 7-9% by weight 14-deoxy-11,12-dehydrogen-andrographolide, and 2-4% by weight neoandrographolide. It is particularly preferred that the extract contain 4.2% by weight andrographolide, 4.4% by weight 14-deoxy-andrographolide, 8% by weight 14-deoxy-11,12-dehydrogen-andrographolide, and 2.1% by weight neoandrographolide.
  • One aspect of this invention relates to a method of inhibiting expression of TNF ⁇ or IL-1 ⁇ in a subject.
  • the method includes administering to the subject an effective amount of the above-described extract.
  • Another aspect of this invention relates to a method of treating a disorder related to TNF ⁇ or IL-1 ⁇ , i.e., inflammatory bowel disease (including Crohn's disease and ulcerative colitis), chronic heart failure, diabetes mellitus, systemic lupus erythematosus, polymyositis/dennatomyositis, psoriasis, acute myelogenous leukemia, AIDS dementia complex, hematosepsis, septic shock, graft-versus-host disease, uveitis, asthma, acute pancreatitis, or periodontal disease.
  • the method includes administering to a subject in need of the treatment an effective amount of the above-described extract.
  • compositions containing the extract of this invention described above for use in treating TNF ⁇ related disorders and IL-1 ⁇ related disorders as well as the use of such a composition for the manufacture of a medicament for treating these disorders.
  • This invention includes methods of inhibiting expression of TNF ⁇ or IL- ⁇ , treating a TNF ⁇ related-disorder, and treating an IL- ⁇ -realted disorder by administering to a subject in need thereof an effective amount of the above-described extract.
  • an effective amount refers to the amount of the extract which is required to confer one of the above-described 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.
  • treating refers to administering the extract to a subject that has a TNF ⁇ related disorder or an IL- ⁇ related disorder, or has a symptom of the disorder, or has a predisposition toward the disorder, with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve, or affect the disorder, the symptoms of the disorder, or the predisposition toward the disorder.
  • an extract for use in this invention one can immerse the aerial part of Andrographis paniculata in one or more suitable solvents, e.g., ethanol, methanol, and acetone; separate the liquid from the solid residue; and concentrate the liquid.
  • suitable solvents e.g., ethanol, methanol, and acetone
  • the extract thus obtained may be further processed. For example, one can remove impurities or modify the ratio of the components by chromatography.
  • 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.
  • useful diluents include lactose and dried corn starch.
  • 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 he 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-10 expression.
  • the extract can further be examined for its efficacy in treating a TNF ⁇ related disorder or an IL-1 ⁇ related disorder by in vivo assays.
  • the extract can be administered to an animal (e.g., a mouse model) having a TNF ⁇ or IL-1 ⁇ related disorder and its therapeutic effects are then accessed. Based on the results, an appropriate dosage range and administration route can also be determined.
  • PBMC Peripheral blood monocytes
  • TNF ⁇ and IL-1 ⁇ were measured using the TNF ⁇ ELISA (Enzyme Linked Immunosorbent Assay) Kit and IL1- ⁇ ELISA Kit (Jingmei Bioengineer Technology).
  • the inhibition ratio was calculated as follows:
  • Inhibition Ratio (%) ( 1 - C extract - C Control C LPS - C Control ) ⁇ 100 where 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, and C Control is the concentration of TNF ⁇ or IL-1 ⁇ in PBMC cells without being treated with LPS or the extract.
  • IBD inflammatory bowel disease
  • mice (18-24 g) were anaesthetized with 1% pentobarbital sodium at 0.05 mg/10 g.
  • pentobarbital sodium 1% pentobarbital sodium at 0.05 mg/10 g.
  • TNBS 2,4,6-trinitrobenzenesulfonic acid
  • Blank control mice only received 0.1 ml of 50% ethanol.
  • the mice were treated with the extract of Andrographis paniculata 24 hours and 2 hours prior to the TNBS administration and daily for 5 days after the administration.
  • mice The body weight of each mouse was monitored every day before and after the TNBS administration. The mice were sacrificed 24 hours after the last administration of the extract. Colons were removed and weighed. Furthermore, the colon weight to body weight ratio was calculated and adhesion between colon and other organs was also monitored.
  • mice were treated with the extract of Andrographis paniculata (500 mg/kg/day) prior to the induction of IBD they had a reduced overall mortality rate, less severe wasting syndrome, a lower colon weight to body weight ratio, and a lower IBD score.
  • the bowel wall was sleek and was not adhesive with surrounding tissues.
  • rats treated with the Andrographis paniculata extract had a reduced overall mortality rate, less severe wasting syndrome, a lower colon weight to body weight ratio, and a lower IBD score, compared with those not treated with the extract.

Abstract

This invention relates to a method of inhibiting TNFα or IL-1β expression with an extract of Andrographis paniculata. The extract contains andrographolide, 14-deoxy-andrographolide, 14-deoxy-11,12-dehydrogen-andrographolide, and neoandrographolide.

Description

CROSS REFERENCE TO RELATED APPLICATIONS
Pursuant to 35 USC § 119(e), this application claims priority to U.S. Provisional Application Ser. No. 60/566,477, filed Apr. 28, 2004, the contents of which are incorporated herein by reference. Notice: More than one reissue application has been filed for the reissue of U.S. Pat. No. 7,341,748. The reissue applications are reissue application Ser. No. 12/717,260, and the present application filed herewith. This application is a divisional reissue application of application Ser. No. 12/717,260, filed Mar. 4, 2010, now U.S. Pat. No. Re. 42,718, which is a broadening reissue application of U.S. Pat. No. 7,341,748, which issued, on Mar. 11, 2008, from U.S. application Ser. No. 11/116,678, filed Apr. 27, 2005, and claims the benefit of U.S. Provisional Application No. 60/566,477, filed Apr. 28, 2004, all of which are incorporated herein by reference.
BACKGROUND
Tumor Necrosis Factor alpha (TNF-α), a mononuclear cytokine, is predominantly produced by monocytes and macrophages. It possesses various biological activities: (1) killing cancer cells or inhibiting growth of cancer cells, (2) enhancing phagocytosis of neutrophilic granulocyte, (3) killing infectious pathogens, and (4) increasing expression of adhesion molecules on vascular endothelial cells during inflammatory responses. Disorders related to expression of TNF-α include, but are not limited to, rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, spondyloarthropathies, inflammatory bowel disease (including Crohn's disease and ulcerative colitis), chronic heart failure, systemic lupus erythematosus, scleroderma, sarcoidosis, polymyositis/dermatomyositis, psoriasis, multiple myeloma, myelodysplastic syndrome, acute myelogenous leukemia, Parkinson's disease, AIDS dementia complex, Alzheimer's disease, depression, sepsis, pyoderma gangrenosum, hematosepsis, septic shock, Behcet's syndrome, graft-versus-host disease, uveitis, Wegener's granulomatosis, Sjogren's syndrome, chronic obstructive pulmonary disease, asthma, acute pancreatitis, periodontal disease, cachexia, central nervous system injury, cancer (e.g., lung carcinomas, esophagus carcinoma, gastric adenocarcinoma, and prostate carcinoma), viral respiratory disease, and obesity. See, e.g., Ogata H. et al Curr Pharm Des. 2003; 9(14): 1107-13; Moller D. R. et al J Intern Med. 2003; 253(1): 31-40; Taylor P. C. et al Curr Pharm Des. 2003; 9(14): 1095-106; Wilkinson N. et al Arch Dis Child. 2003; 88(3): 186-91; Nishimura F. et al J Periodontol. 2003; 74(1): 97-102; Weinberg J. M. et al Cutis. 2003; 71(1): 41-5; Burnham E. et al Crit Care Med. 2001; 29(3): 690-1; Sack M. et al Pharmacol Ther. 2002; 94(1-2): 123-35; Barnes P. J. et al Anna Rev Pharmacol Toxicol. 2002; 42:81-98; Mageed R. A. et al Lupus 2002; 11(12): 850-5; Tsimberidou A. M. et al Expert Rev Anticancer Ther. 2002; 2(3): 277-86; Muller T. et al Curr Opin Investig Drugs. 2002; 3(12): 1763-7; Calandra T. et al Curr Clin Top Infect Dis. 2002; 22:1-23; Girolomoni G et al Curr Opin Investig Drugs. 2002; 3(11): 1590-5; Tutuncu Z. et al Clin Exp Rheumatol. 2002; 20(6 Suppl 28): S146-51; Braun J. et al Best Pract Res Clin Rheumatol. 2002; 16(4): 631-51; Barnes P. J. et al Novartis Found Symp. 2001; 234:255-67; discussion 267-72; Brady M. et al Baillieres Best Pract Res Clin Gastroenterol. 1999; 13(2): 265-89; Goldring M. B. et al Expert Opin Biol Ther. 2001; 1(5): 817-29; Mariette X. Rev Prat. 2003; 53(5): 507-11; Sharma R. et al Int J Cardiol. 2002; 85(1): 161-71; Wang C. X. et al Prog Neurobiol. 2002; 67(2): 161-72; Van Reeth K. et al Vet Immunol Immunopathol. 2002; 87(3-4): 161-8; Leonard B. E. et al Int J Dev Neurosci. 2001; 19(3): 305-12; and Hays S. J. et al Curr Pharm Des. 1998; 4(4): 335-48.
Interleukin-1 beta (IL-1β), a cytokine secreted by cells such as monocytes, macrophages and dendritic cells, mediates a wide range of immune and inflammatory responses. One can modulate 1L-1β production to treat a variety of disorders, such as rheumatoid arthritis, hematosepsis, periodontal disease, chronic heart failure, polymyositis/dermatomyositis, acute pancreatitis, chronic obstructive pulmonary disease, Alzheimer's disease, osteoarthritis, bacterial infections, multiple myeloma, myelodysplastic syndrome, uveitis, central nervous system injury, viral respiratory disease, asthma, depression, and scleroderma. See, e.g., Taylor P. C. et al Curr Pharm Des. 2003; 9(14): 1095-106; Dellinger R. P. et al Clin Infect Dis. 2003; 36(10): 1259-65; Takashiba S. et al J Periodontol. 2003; 74(1): 103-10; Diwan A. et al Curr Mol Med. 2003; 3(2): 161-82; Lundberg I. E. et al Rheum Dis Clin North Am. 2002; 28(4): 799-822; Makhija R. et al J Hepatabiliary Pancreat Surg. 2002; 9(4): 401-10; Chung K. F. et al Eur Respir J Suppl. 2001; 34:50s-59s; Hallegua D. S. et al Ann Rheum Dis. 2002; 61(11): 960-7; Goldring M. B. et al Expert Opin Biol Ther. 2001; 1(5): 817-29; Mrak R. E. et al Neurobiol Aging. 2001; 22(6): 903-8; Brady M. et al Baillieres Best Pract Res Clin Gastroenterol. 1999; 13(2): 265-89; Van der Meer J. W. et al Ann N Y Acad Sci. 1998; 856:243-51; Rameshwar P. et al Acta Haematol 2003; 109(1): 1-10; de Kozak Y et al Int Rev Immunol. 2002; 21(2-3): 231-53; Wang C. X. et al Prog Neurobiol. 2002; 67(2): 161-72; Van Reeth K. et al Vet Immunol Immunopathol. 2002; 87(3-4): 161-8; Stirling R. G. et al Br Med Bull. 2000; 56(4): 1037-53; Leonard B. E. et al Int J Dev Neurosci. 2001; 19(3): 305-12; Allan S. M. et al Ann N Y Acad Sci. 2000; 917:84-93; and Cafagna D. et al Minerva Med. 1998; 89(5): 153-61.
SUMMARY
This invention is based on a surprising discovery that an extract of Andrographis paniculata inhibits expression of both TNFα and IL-1β. The extract, obtained from the aerial part of Andrographis paniculata, contains andrographolide, 14-deoxy-andrographolide, 14-deoxy-11,12-dehydrogen-andrographolide, and neoandrographolide. Preferably, the extract contains 2-20% by weight andrographolide, 1-6% by weight 14-deoxy-andrographolide, 1-12% by weight 14-deoxy-11,12-dehydrogen-andrographolide, and 1-5% by weight neoandrographolide. More preferably, the extract contains 3-8% by weight andrographolide, 3-5% by weight 14-deoxy-andrographolide, 7-9% by weight 14-deoxy-11,12-dehydrogen-andrographolide, and 2-4% by weight neoandrographolide. It is particularly preferred that the extract contain 4.2% by weight andrographolide, 4.4% by weight 14-deoxy-andrographolide, 8% by weight 14-deoxy-11,12-dehydrogen-andrographolide, and 2.1% by weight neoandrographolide.
One aspect of this invention relates to a method of inhibiting expression of TNFαor IL-1β in a subject. The method includes administering to the subject an effective amount of the above-described extract.
Another aspect of this invention relates to a method of treating a disorder related to TNFα or IL-1β, i.e., inflammatory bowel disease (including Crohn's disease and ulcerative colitis), chronic heart failure, diabetes mellitus, systemic lupus erythematosus, polymyositis/dennatomyositis, psoriasis, acute myelogenous leukemia, AIDS dementia complex, hematosepsis, septic shock, graft-versus-host disease, uveitis, asthma, acute pancreatitis, or periodontal disease. The method includes administering to a subject in need of the treatment an effective amount of the above-described extract.
Also within the scope of this invention is a composition containing the extract of this invention described above for use in treating TNFα related disorders and IL-1β related disorders as well as the use of such a composition for the manufacture of a medicament for treating these disorders.
Details of several embodiments of the invention are set forth in the description below. Other features, objects, and advantages of the invention will be apparent from the description, and also from the claims.
DETAILED DESCRIPTION
This invention includes methods of inhibiting expression of TNFα or IL-β, treating a TNFα related-disorder, and treating an IL-β-realted disorder by administering to a subject in need thereof an effective amount of the above-described extract. The term “an effective amount” refers to the amount of the extract which is required to confer one of the above-described 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. The term “treating” refers to administering the extract to a subject that has a TNFα related disorder or an IL-β related disorder, or has a symptom of the disorder, or has a predisposition toward the disorder, with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve, or affect the disorder, the symptoms of the disorder, or the predisposition toward the disorder.
To prepare an extract for use in this invention, one can immerse the aerial part of Andrographis paniculata in one or more suitable solvents, e.g., ethanol, methanol, and acetone; separate the liquid from the solid residue; and concentrate the liquid. The extract thus obtained may be further processed. For example, one can remove impurities or modify the ratio of the components by chromatography.
To practice one of the above-described methods, one administers to a subject in need thereof orally, rectally, parenterally, by inhalation spray, or via an implanted reservoir a composition that is either the above-mentioned extract alone or a mixture of the extract and a pharmaceutically acceptable carrier. The term “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. For oral administration in a capsule form, useful diluents include lactose and dried corn starch. When aqueous suspensions or emulsions are administered orally, 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 sterile injectable composition (e.g., aqueous or oleaginous suspension) 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. Among the acceptable vehicles and solvents that can be employed are mannitol, water, Ringer's solution and isotonic sodium chloride solution. In addition, 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. Additionally, 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 he 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. For example, 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 TNFα or IL-10 expression. The extract can further be examined for its efficacy in treating a TNFα related disorder or an IL-1β related disorder by in vivo assays. For example, the extract can be administered to an animal (e.g., a mouse model) having a TNFα or IL-1β related disorder and its therapeutic effects are then accessed. Based on the results, an appropriate dosage range and administration route can also be determined.
Without further elaboration, it is believed that the above description has adequately enabled the present invention. The following specific examples are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever. All of the publications, including patents, cited herein are hereby incorporated by reference in their entirety.
Preparation of an Extract of Andrographis paniculata
Dried powder of the aerial part of Andrographis paniculata (1 kg) was suspended in 85% ethanol. The suspension was refluxed for two hours and filtered. The residue was extracted with 85% ethanol again. The combined ethanol solutions were cooled and concentrated to afford 105 g of the desired extract. HPLC analysis shows that the extract contained 4.0% andrographolide.
In vitro Assay
An in vitro assay was conducted to evaluate the efficacy of the Andrographis paniculata extract in inhibiting expression of TNFα and IL-1β expression. Peripheral blood monocytes (PBMC) cells were isolated from fresh blood using the Ficoll-Paque Plus (Amersham Bioscience) according to the protocol recommended by the manufacturer. The cells were suspended in RPMI 1640 media containing 10% FBS at a concentration of 1×105 cells/ml and seeded in a 96-well plate (1×104 cells total in each well). Each reaction was carried out in three wells.
10 μl of the Andrographis paniculata extract in DMSO was added into each well (final concentrations: 0.1, 0.3, 1, 3, 10, and 30 μg/ml). Wells containing dexamethason (Cal-Biochem.) at the final concentration of 10 μM were used as positive control. Wells containing 10 μl of the media were used as negative control. The plate was incubated at 37° C. under 5% CO2 for 15 minutes. After 10 μl aliquots of 100 μg/ml lipopolysaccharide were added to all wells except for the negative control, the plate was incubated at 37° C. under 5% CO2 overnight.
The plate was spun at 1000 rpm for 15 minutes and the supernatants were collected. Concentrations of TNFα and IL-1β were measured using the TNFα ELISA (Enzyme Linked Immunosorbent Assay) Kit and IL1-β ELISA Kit (Jingmei Bioengineer Technology).
The inhibition ratio was calculated as follows:
Inhibition  Ratio  (%) = ( 1 - C extract - C Control C LPS - C Control ) × 100
where Cextract is the concentration of TNFα or IL-1β in PBMC cells treated with the extract and LPS, CLPS is the concentration of TNFα or IL-1β in PBMC cells treated with LPS and dexamethason, and CControl is the concentration of TNFα or IL-1β in PBMC cells without being treated with LPS or the extract.
The results show that the extract significantly inhibited expression of both TNFα and IL-1β.
In vivo Assays
In vivo assays were conducted to evaluate the efficacy of the Andrographis paniculata extract in treating inflammatory bowel disease (IBD).
Balb/c male mice (18-24 g) were anaesthetized with 1% pentobarbital sodium at 0.05 mg/10 g. To induce IBD, 1.5 mg of 2,4,6-trinitrobenzenesulfonic acid (TNBS; Sigma) in 50% ethanol was administered slowly to each mouse (except blank control mice) via a catheter. Blank control mice only received 0.1 ml of 50% ethanol. The mice were treated with the extract of Andrographis paniculata 24 hours and 2 hours prior to the TNBS administration and daily for 5 days after the administration.
The body weight of each mouse was monitored every day before and after the TNBS administration. The mice were sacrificed 24 hours after the last administration of the extract. Colons were removed and weighed. Furthermore, the colon weight to body weight ratio was calculated and adhesion between colon and other organs was also monitored.
Samples of colon tissues located precisely 2 cm above the anal canal were obtained, fixed in 10% buffered phosphate, embedded in paraffin, sectioned, and stained with hematoxylin/eosin. The degree of inflammation on microscopic cross sections was 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 results show that when mice were treated with 150 mg/kg TNBS alone, they had severe illness characterized by diarrhea, profound and sustained weight losses, a significant increase of the colon weight to body weight ratio, and a mortality rate of 50%. Macroscopic examination indicates that the colon of each of mice had transmural inflammation in all layers of the bowel wall. In contrast, when mice were treated with the extract of Andrographis paniculata (500 mg/kg/day) prior to the induction of IBD, they had a reduced overall mortality rate, less severe wasting syndrome, a lower colon weight to body weight ratio, and a lower IBD score. The bowel wall was sleek and was not adhesive with surrounding tissues.
In a separate assay, male Wistar rats were used to evaluate the efficacy of the Andrographis paniculata extract in treating IBD following a procedure similar to that described above. To induce IBD, the rats were administered with 2,4-dinitrobenzenesulfonic acid, instead of TNBS.
Similar results were obtained. Specifically, rats treated with the Andrographis paniculata extract had a reduced overall mortality rate, less severe wasting syndrome, a lower colon weight to body weight ratio, and a lower IBD score, compared with those not treated with the extract.
OTHER EMBODIMENTS
A number of embodiments of the invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are also within the scope of the following claims.

Claims (13)

1. A method of treating an inflammatory bowel disease in a subject in need thereof, comprising administering to the subject an effective amount of an extract of Andrographis-paniculata, wherein the extract contains 2-20% by weight andrographolide, 1-6% by weight 14-deoxy-andrographolide, 1-12% by weight 14-deoxy-11,12-dehydrogen-andrographolide, and 1-5% by weight neoandrographolide.
2. The method of claim 1, wherein the extract contains 3-8% by weight andrographolide, 3-5% by weight 14-deoxy-andrographolide, 7-9% by weight 14-deoxy-11,12-dehydrogen-andrographolide, and 2-4% by weight neoandrographolide.
3. The method of claim 2, wherein the extract contains 4.2% by weight andrographolide, 4.4% by weight 14-deoxy-andrograpliolide, 8% by weight 14-deoxy-11,12-dehydrogen-andrographolide, and 2.1% by weight neoandrographolide.
4. The method of claim 1, wherein the inflammatory bowel disease is Crohn's disease.
5. The method of claim 1, wherein the inflammatory bowel disease is ulcerative colitis.
6. The method of claim 5, wherein the extract contains 3-8% by weight andrographolide, 3-5% by weight 14-deoxy-andrographolide, 7-9% by weight 14-deoxy-11,12-dehydrogen-andrographolide, and 2-4% by weight neoandrographolide.
7. The method of claim 6, wherein the extract contains 4.2% by weight andrographolide, 4.4% by weight 14-deoxy-andrographolide, 8% by weight 14-deoxy-11,12-dehydrogen-andrographolide, and 2.1% by weight neoandrographolide.
8. An extract of Andrographis paniculata for treating effectively an inflammatory bowel disease in a subject in recognized need thereof, comprising: 2-20% by weight andrographolide, 1.0-7% by weight 14-deoxy-11,12-dehydrogen-andrographolide, and further comprising in said extract for treating effectively an inflammatory bowel disease, 1-5% by weight neoandrographolide.
9. The extract of claim 8, wherein said extract comprises 3-8% by weight andrographolide, 1.0-7% by weight 14-deoxy-11,12-dehydrogen-andrographolide, and 2-4% by weight neoandrographolide.
10. An extract of Andrographis paniculata, for treating effectively an inflammatory bowel disease in a subject in recognized need thereof, comprising: 2-20% by weight andrographolide, 14-deoxy-andrographolide, 1.0-7% by weight 14-deoxy-11,12-dehydrogen-andrographolide, and further comprising in said extract for treating effectively an inflammatory bowel disease, 1-5% by weight neoandrographolide.
11. The extract of claim 10, wherein said extract comprises 3-8% by weight andrographolide, 14-deoxy-andrographolide, 1.0-7% by weight 14-deoxy-11,12-dehydrogen-andrographolide, and 2-4% by weight neoandrographolide.
12. A pharmaceutical composition for treating effectively an inflammatory bowel disease in a subject in recognized need thereof, comprising an extract of Andrographis paniculata, comprising: 2-20% by weight andrographolide, 1.0-7% by weight 14-deoxy-11,12-dehydrogen-andrographolide, and 1-5% by weight neoandrographolide and further comprising a pharmaceutical composition for treating effectively an inflammatory bowel disease in a subject in recognized need thereof, a pharmaceutically acceptable carrier.
13. A pharmaceutical composition for treating effectively an inflammatory bowel disease in a subject in recognized need thereof, comprising an extract of Andrographis paniculata, comprising: 2-20% by weight andrographolide, 14-deoxy-andrographolide, 1.0-7% by weight 14-deoxy-11,12-dehydrogen-andrographolide, and 1-5% by weight neoandrographolide and further comprising a pharmaceutical composition for treating effectively an inflammatory bowel disease in a subject in recognized need thereof, a pharmaceutically acceptable carrier.
US13/189,444 2004-04-28 2011-07-22 Crude extracts from Andrographis paniculata Active USRE43423E1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US13/189,444 USRE43423E1 (en) 2004-04-28 2011-07-22 Crude extracts from Andrographis paniculata

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US56647704P 2004-04-28 2004-04-28
US11/116,678 US7341748B2 (en) 2004-04-28 2005-04-27 Crude extracts from Andrographis paniculata
US12/717,260 USRE42718E1 (en) 2004-04-28 2010-03-04 Crude extracts from andrographis paniculata
US13/189,444 USRE43423E1 (en) 2004-04-28 2011-07-22 Crude extracts from Andrographis paniculata

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US11/116,678 Reissue US7341748B2 (en) 2004-04-28 2005-04-27 Crude extracts from Andrographis paniculata

Publications (1)

Publication Number Publication Date
USRE43423E1 true USRE43423E1 (en) 2012-05-29

Family

ID=35242143

Family Applications (3)

Application Number Title Priority Date Filing Date
US11/116,678 Ceased US7341748B2 (en) 2004-04-28 2005-04-27 Crude extracts from Andrographis paniculata
US12/717,260 Active USRE42718E1 (en) 2004-04-28 2010-03-04 Crude extracts from andrographis paniculata
US13/189,444 Active USRE43423E1 (en) 2004-04-28 2011-07-22 Crude extracts from Andrographis paniculata

Family Applications Before (2)

Application Number Title Priority Date Filing Date
US11/116,678 Ceased US7341748B2 (en) 2004-04-28 2005-04-27 Crude extracts from Andrographis paniculata
US12/717,260 Active USRE42718E1 (en) 2004-04-28 2010-03-04 Crude extracts from andrographis paniculata

Country Status (14)

Country Link
US (3) US7341748B2 (en)
EP (1) EP1747008B1 (en)
JP (1) JP5221128B2 (en)
KR (3) KR101536892B1 (en)
AU (1) AU2005237550B2 (en)
CA (1) CA2564637C (en)
DK (1) DK1747008T3 (en)
ES (1) ES2534594T3 (en)
HU (1) HUE025117T2 (en)
PL (1) PL1747008T3 (en)
PT (1) PT1747008E (en)
RU (1) RU2383353C2 (en)
TW (1) TWI373340B (en)
WO (1) WO2005104722A2 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090117210A1 (en) * 2007-11-02 2009-05-07 Hutchison Medipharma Enterprises Limited Andrographis paniculata extract
US20110142944A1 (en) * 2006-02-28 2011-06-16 Hutchison Medipharma Enterprises Limited, Offshore Group Chambers Andrographis extract formulations

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW200536526A (en) * 2004-03-11 2005-11-16 Hutchison Medipharma Entpr Ltd Andrographolide and analogues as inhibitors of TNF-alpha and IL-1 β expression
ES2534594T3 (en) 2004-04-28 2015-04-24 Nutrition Science Partners Limited Raw extracts of Andrographis paniculata
JP2007176934A (en) * 2005-11-30 2007-07-12 Kose Corp Platelet-activating factor acetylhydrolase function regulator
EP1882473A1 (en) * 2006-07-28 2008-01-30 Indena S.P.A. Use of anthocyanosides to prepare formulations for the treatment of mucositis induced by antitumoral drugs
WO2010110748A1 (en) * 2009-03-24 2010-09-30 National University Of Singapore Use of andrographolide compounds for treating inflammation and airway disorders
MD480Z (en) * 2011-07-07 2012-09-30 Elvira Andon Method for treating acute ulcerative nonspecific colitis
CN102702147B (en) * 2012-06-18 2016-06-08 辽宁利锋科技开发有限公司 The application of andrographolide analog and treatment thereof
CN103145661B (en) * 2013-03-25 2014-06-18 成都天台山制药有限公司 New crystal form of andrographolide
CN103145660B (en) * 2013-03-25 2014-09-17 成都天台山制药有限公司 Andrographolide and preparation method thereof
CN103223028A (en) * 2013-03-27 2013-07-31 张宗升 Extract product of traditional Chinese medicine
CN103766901A (en) * 2014-01-08 2014-05-07 浙江大学 Application of andrographolide C to preparation of weight-losing food or medicine
JP6386761B2 (en) * 2014-03-19 2018-09-05 花王株式会社 Involucrin expression inhibitor
MY176459A (en) 2016-05-23 2020-08-10 Univ Putra Malaysia Extract of andrographis paniculata for cognitive enhancement
WO2018081959A1 (en) 2016-11-02 2018-05-11 Nutrition Science Partners Limited Extracts of andrographis paniculata, methods for preparation and use thereof
CN107349253A (en) * 2017-06-23 2017-11-17 苏州凌科特新材料有限公司 Non-stimulated Medical antiseptic solution and preparation method thereof
WO2022058422A1 (en) * 2020-09-17 2022-03-24 Dsm Ip Assets B.V. Use of andrographis paniculata extract to protect against air pollution related diseases

Citations (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1042077A (en) 1989-07-29 1990-05-16 郭如明 Alkali-water process for creat
JP2000034233A (en) 1998-07-15 2000-02-02 Sumitomo Forestry Co Ltd Inhibitor of production of nitric oxide
JP2001058969A (en) 1999-08-20 2001-03-06 Nettairin Saisei Gijutsu Kenkyu Kumiai Nitrogen monoxide production inhibitor
US6358526B1 (en) 2000-08-16 2002-03-19 Rexall Sundown Method of making tablets and tablet compositions produced therefrom
US20020068098A1 (en) 2000-08-01 2002-06-06 Ashni Naturaceuticals, Inc. Combinations of diterpene triepoxide lactones and ditepene lactones or triterpenes for synergistic inhibition of cyclooxygenase-2
US20030059471A1 (en) 1997-12-15 2003-03-27 Compton Bruce Jon Oral delivery formulation
US20030091517A1 (en) 2001-11-09 2003-05-15 Mahidol University Andrographis paniculata gel as an adjunct in the treatment of periodontitis
US20030101076A1 (en) 2001-10-02 2003-05-29 Zaleski John R. System for supporting clinical decision making through the modeling of acquired patient medical information
US20030104076A1 (en) 2001-11-07 2003-06-05 Wilhelm Berkulin Process for preparing dry extracts
JP2004075638A (en) 2002-08-21 2004-03-11 Okinawa Pref Gov Functional material having action to suppress increase of blood sugar level and suppress increase of blood pressure
US20040053858A1 (en) 2000-07-28 2004-03-18 Berg Kurt Frimann Method of treating symptoms of common cold, allergic rhinitis and infections relating to the respiratory tract
CN1488376A (en) 2003-05-09 2004-04-14 江西诚志信丰药业有限责任公司 Medicinal cap sule for treating enteric disease and nusosinusitis and preparing method thereof
US20040151792A1 (en) 2001-06-20 2004-08-05 Tripp Matthew L. Compositions that treat or inhibit pathological conditions associated with inflammatory response
CN1626076A (en) 2003-12-11 2005-06-15 天津天士力制药股份有限公司 Andrographolide drop pills and preparation method
CN1628764A (en) 2004-08-19 2005-06-22 贵阳云岩西创药物科技开发有限公司 Creat formulation and its preparation process
KR20050067951A (en) 2003-12-29 2005-07-05 주식회사 엘지생활건강 Andrographolide or andrographis paniculata extract containing composition having anti-itching effect
WO2005087223A1 (en) 2004-03-11 2005-09-22 Hutchison Medipharma Ltd. ANDROGRAPHOLIDE AND ANALOGUES AS INHIBITORS OF TNFα AND IL-1βEXPRESSION
WO2005104722A2 (en) 2004-04-28 2005-11-10 Hutchison Medipharma Enterprises Limited Crude extracts from andrographis paniculata
US20070202164A1 (en) 2006-02-28 2007-08-30 Hutchison Medipharma Enterprises Limited Andrographis Extract Formulations
US20070218114A1 (en) 2004-06-12 2007-09-20 Passionfor Life Healthcare Limited Soluble Strip for Oral or Topical Administration
WO2009059158A1 (en) 2007-11-02 2009-05-07 Hutchison Medipharma Enterprises Limited Andrographis paniculata extract

Patent Citations (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1042077A (en) 1989-07-29 1990-05-16 郭如明 Alkali-water process for creat
US20030059471A1 (en) 1997-12-15 2003-03-27 Compton Bruce Jon Oral delivery formulation
JP2000034233A (en) 1998-07-15 2000-02-02 Sumitomo Forestry Co Ltd Inhibitor of production of nitric oxide
JP2001058969A (en) 1999-08-20 2001-03-06 Nettairin Saisei Gijutsu Kenkyu Kumiai Nitrogen monoxide production inhibitor
US20040053858A1 (en) 2000-07-28 2004-03-18 Berg Kurt Frimann Method of treating symptoms of common cold, allergic rhinitis and infections relating to the respiratory tract
US20020068098A1 (en) 2000-08-01 2002-06-06 Ashni Naturaceuticals, Inc. Combinations of diterpene triepoxide lactones and ditepene lactones or triterpenes for synergistic inhibition of cyclooxygenase-2
US6358526B1 (en) 2000-08-16 2002-03-19 Rexall Sundown Method of making tablets and tablet compositions produced therefrom
US20040151792A1 (en) 2001-06-20 2004-08-05 Tripp Matthew L. Compositions that treat or inhibit pathological conditions associated with inflammatory response
US20030101076A1 (en) 2001-10-02 2003-05-29 Zaleski John R. System for supporting clinical decision making through the modeling of acquired patient medical information
US20030104076A1 (en) 2001-11-07 2003-06-05 Wilhelm Berkulin Process for preparing dry extracts
US20030091517A1 (en) 2001-11-09 2003-05-15 Mahidol University Andrographis paniculata gel as an adjunct in the treatment of periodontitis
JP2004075638A (en) 2002-08-21 2004-03-11 Okinawa Pref Gov Functional material having action to suppress increase of blood sugar level and suppress increase of blood pressure
CN1488376A (en) 2003-05-09 2004-04-14 江西诚志信丰药业有限责任公司 Medicinal cap sule for treating enteric disease and nusosinusitis and preparing method thereof
CN1626076A (en) 2003-12-11 2005-06-15 天津天士力制药股份有限公司 Andrographolide drop pills and preparation method
KR20050067951A (en) 2003-12-29 2005-07-05 주식회사 엘지생활건강 Andrographolide or andrographis paniculata extract containing composition having anti-itching effect
WO2005087223A1 (en) 2004-03-11 2005-09-22 Hutchison Medipharma Ltd. ANDROGRAPHOLIDE AND ANALOGUES AS INHIBITORS OF TNFα AND IL-1βEXPRESSION
US20050215628A1 (en) 2004-03-11 2005-09-29 Hutchison Medipharma Ltd. Andrographolide and analogues as inhibitors of TNFalpha and IL-1beta expression
US7625945B2 (en) 2004-03-11 2009-12-01 Hutchison MediPharma Enterprises Ltd. Andrographolide and analogues as inhibitors of TNFα and IL-1β expression
WO2005104722A2 (en) 2004-04-28 2005-11-10 Hutchison Medipharma Enterprises Limited Crude extracts from andrographis paniculata
US20060246156A1 (en) 2004-04-28 2006-11-02 Hutchinson Medipharma Enterprises Limited Crude extracts from andrographis paniculata
US7341748B2 (en) 2004-04-28 2008-03-11 Hutchison Medipharma Enterprises Limited Crude extracts from Andrographis paniculata
US20070218114A1 (en) 2004-06-12 2007-09-20 Passionfor Life Healthcare Limited Soluble Strip for Oral or Topical Administration
CN1628764A (en) 2004-08-19 2005-06-22 贵阳云岩西创药物科技开发有限公司 Creat formulation and its preparation process
WO2007098686A1 (en) 2006-02-28 2007-09-07 Hutchison Medipharma Enterprises Limited Andrographis extract formulations
US20070202164A1 (en) 2006-02-28 2007-08-30 Hutchison Medipharma Enterprises Limited Andrographis Extract Formulations
WO2009059158A1 (en) 2007-11-02 2009-05-07 Hutchison Medipharma Enterprises Limited Andrographis paniculata extract
US20090117209A1 (en) 2007-11-02 2009-05-07 Hutchison Medipharma Enterprises Limited Andrographis paniculata extract
US20090117210A1 (en) 2007-11-02 2009-05-07 Hutchison Medipharma Enterprises Limited Andrographis paniculata extract

Non-Patent Citations (173)

* Cited by examiner, † Cited by third party
Title
Achike et al., "Nitric Oxide, Human Diseases and the Herbal Products that Effect the Nitric Oxide Signalling Pathway," Clinical & Experimental Pharmacology & Physiology, 30: 605-615 (2003).
Advisory Action mailed Mar. 25, 2011, in Reissue U.S. Application No. 12/717,260.
Akbarsha et al., "Antifertility effect of Andrographis paniculata (nees) in male albino rat," Indian Journal of Experimental Biology, 28:421-426 (1990).
Akbarsha et al., Antifertility effect of Andrographis paniculata (nees) in male albino rat, Indian Journal of Experimental Biology, 28:421-426, 1990.
Amendment and Reply Under 37 C.F.R. § 1.114 filed Sep. 18, 2009, in U.S. Appl. No. 11/934,143.
Amendment and Reply under 37 U.S.C. § 1.114, filed Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
Amendment and Response to Election Requirement filed Apr. 13, 2011, in U.S. Appl. No. 12/264,646.
Amendment in Reply to Action of Aug. 1, 2006 filed Dec. 1, 2006, in U.S. Appl. No. 11/116,678.
Amendment in reply to Communication pursuant to Article 94(3) EPC of Dec. 3, 2009 filed Jun. 3, 2010, in EP 1747008.
Amendment in Reply to Non-Final Office Action of Jul. 7, 2008 with Exhibits A & B, filed Nov. 7, 2008, in U.S. Appl. No. 11/934,143.
Andrographis Paniculata Tablets, The Pharmacopoeia of People's Republic of China (2000 ed.), vol. I, p. 541 (2000).
Andrographis Paniculata Tablets, The Pharmacopoeia of People's Republic of China (2005 ed.), vol. I, pp. 549-550 (2005).
Assche et al., "Daclizumab, a humanised monoclonal antibody to the interleukin 2 receptor (CD25), for the treatment of moderately to severely active ulcerative colitis: a randomised, double blind, placebo controlled, dose ranging trial," Gut 55;1568-1574 (2006).
Balmain et al., "Minor Diterpenoid Constituents of Andrographis paniculata Nees," J. Chem. Soc. Perkin. Trans. I (1973): 1247-1251.
Bao W., "Determination of Dehydroandrographolide in Andrographis paniculata Tablets by FIA," Chinese Traditional Patent Medicine, 25(12):976-978 (2003).
Basak et al., "Implication of the protein convertases furin, PC5 and PC7 in the cleavage of surface glycoproteins of Hong Kong, Ebola and respiratory syncytial viruses: a comparative analysis with fluorogenic peptides," Biochem J., 353:537-545 (2001).
Basak et al., "Implication of the protein convertases furin, PC5 and PC7 in the cleavage of surface glycoproteins of Hong Kong, Ebola and respiratory syncytial viruses: a comparative analysis with fluorogenic peptides", Biochem J., 353:537-45, 200, abstract.
Bhan et al., "Screening and optimization of Andrographis paniculata (Burm.f.) Nees for total andrographolide content, yield and its components," Scientia Horticulturae, 107: 386-391 (2006).
Burgos et al., "Testicular toxicity assessment of Andrographis paniculata dried extract in rats," J. Ethnopharmacol., 58(3): 219-224 (1997).
Cai S., et al., "Factors impacting the determination of andrographolide and dehydroandrographolide content in Andrographis paniculata tablets," Chinese Traditional Patent Medicine, 27(3):361-362 (2005).
Calabrese et al., "A Phase I Trial of Andrographolide in HIV Positive Patients and Normal Volunteers," Phytother Res., 14:333-338 (2000).
Calabrese et al., A Phase I Trial of Andrographolide in HIV Positive Patients and Normal Volunteers, Phytother. Res. 14:333-338, 2000.
Chang et al., "Dehydroandrographolide succinic acid monoester as an inhibitor against the human immunodeficiency virus," Proc. Soc. Exp. Biol. Med., 197(1): 59-66 (1991).
Chen et al. , "Studies on flavonoids of Andrographis paniculata, " China J. Chinese Materia Medica., 31(5):391-395 (2006), Abstract only.
Chen et al., "Nine new ent-labdane diterpenoids from the aerial parts of Andrographis paniculata," Helvetica Chimica Acta, 89:2654-2664 (2006).
Chen et al., "Studies on diterpenoids from Andrographis paniculata," China J. Chinese Materia Medica., 31(19):1594-1597 (2006), Abstract only.
Communication pursuant to Article 94(3) EPC in EP 1747008, dated Dec. 3, 2009.
Communication pursuant to Article 94(3) EPC in EP 1747008, dated Feb. 24, 2011.
Communication pursuant to Article 94(3) EPC in EP 1747008, dated Jul. 5, 2010.
Communication pursuant to Article 94(3) EPC in European Patent Application No. 05742174.5, dated Sep. 27, 2011.
Communication pursuant to Rule 114(2) EPC in EP1996165, dated Apr. 29, 2010, enclosing Third Party Observations.
Coon et al., "Andrographis paniculata in the Treatment of Upper Respiratory Tract Infections: A Systematic Review of Safety and Efficacy," Planta Med., 70(4): 293-298 (2004).
Deng et al., Chinese Pharm. Bull., 17:195-198 (1982), Abstract only.
English translation of JP 2000034233 A-2000. *
Ex parte Subramanyam (BPAI, Mar. 29, 2010).
Feagan et al., "Omega-3 Free Fatty Acids for theMaintenance of Remission in Crohn Disease," JAMA, 299(14):1690-1697 (2008).
Feng Y., et al., "Determination of deoxyandrographolide content in Andrographis paniculata tablets by TLC scanning," Chinese Traditional Patent Medicine, 14(5):17-18 (1992).
Final Office Action mailed Feb. 21, 2007, in U.S. Appl. No. 11/116,678.
Final Office Action mailed Feb. 9, 2011, in Reissue U.S. Appl. No. 12/717,260.
Final Office Action mailed Jan. 4, 2010, in U.S. Appl. No. 11/674,557.
Final Office Action mailed Jun. 16, 2010, in U.S. Appl. No. 11/934,143.
Final Office Action mailed Mar. 20, 2009, in U.S. Appl. No. 11/934,143.
Final Office Action mailed Oct. 18, 2011, in U.S. Appl. No. 11/934,143.
Fujita et al., "On the diterpenoids of Andrographis paniculata: x-ray Crystallographic analysis of andrographolide and structure determination of new minor diterpenoids," Chem. Pharm. Bull., 32(6):2117-2125 (1984).
George et al., "Investigations on plant antibiotics. Part IV. Further search for antibiotic substances in Indian medicinal plants," Indian Journal of Medical Research, (37): 169-181 (2004).
Ghosh et al., "Isolation of Andrographis paniculata leaf protein with antifungal property," Acto. Phytopathologica et Entomologica Hungarica, 39(4):377-381 (2004).
Guidance for Industry Botanical Drug Products, U.S. Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Jun. 2004.
Gupta et al., "Antidiarrheal activity of diterpenes of Andrographis paniculata (kalmegh) against Escherichia coli enterotoxin in in vivo models," International Journal of Crude Drug Research, (28): 273-283 (1990).
Gupta et al., "Antisecretory (antidiarrhoeal) activity of Indian medicinal plants against Escherichia coli enterotoxin-induced secretion in rabbit and guinea pig ileal loop models," lnl. J, Pharmacog., 31(3):198-204 (1993).
Gupta et al., "Flavonoid glycoside of Andrographis paniculata," Indian J. Chem., 35 B:512-513 (1996).
Gupta et al., "Flavonoids of Andrographis paniculata," Phytochemistry, 22(1):314-315 (1983).
Habtemariam, "Andrographolide inhibits the tumour necrosis Factor-alpha-induced upregulation of ICAM-1 expression and endothelial-monocyte adhesion," Phytotherapy Research, 12:37-40 (1998).
Habtemariam, "Natural Inhibitors of Tumor Necrosis Factor-alpha Production, Secretion and Function," Planta Medica, 66:303-313 (2000).
Habtemariam, "Andrographolide Inhibits the Tumor Necrosis Factor-Alpha-Induced Upregulation of ICAM-1 Expression and Endothelial-Monocyte Adhesion" Phytotherapy Research (1998) vol. 12, No. 1, pp. 37-40, abstract.
Habtemariam, "Andrographolide inhibits the tumour necrosis Factor-α-induced upregulation of ICAM-1 expression and endothelial-monocyte adhesion," Phytotherapy Research, 12:37-40 (1998).
Habtemariam, "Natural Inhibitors of Tumor Necrosis Factor-α Production, Secretion and Function," Planta Medica, 66:303-313 (2000).
Habtemariam, S., "Andrographolide inhibits the tumor necrosis factor-.alpha .-induced upregulation of ICAM-1 expression and endothelial-monocyte adhesion", Phytotherapy Research, 12(1):37-40, 1998, abstract.
Hancke et al., "A double-blind study with a new monodrug: decrease of symptoms and improvement of recovery from common colds," Phytotherapy Research, (9): 559-562 (1995).
Hasko, Immunology, 103L 473-478 (2001).
Herba Andrographis, World Health Organization (WHO) monographs on selected medicinal plants, vol. 2. pp. 12-24 (2002).
Herbs, Andrographis paniculata's wide range of medicinal Powers, (2002).
Huang P. et al., "Determination of dehydroandrographolide content in Andrographis paniculata tablets by HPLC," Journal of Guangxi Traditional Chinese Medical University, 7(3):70-71 (2004).
Jalal et al., "Formation of three new Flavones by differentiating callus cultures of Andrographis paniculata," Phytochemistry, 18:149-151 (1979).
Jantan et al., "Ent-14beta-Hydroxy-8(17),12-Labdadien-16,15-Olide-3beta,19 Oxdide: a Diterpene from the aerial parts of Andrographis paniculata," Phytochemistry, 37(5):1477-1479 (1994).
Jantan et al., "Ent-14β-Hydroxy-8(17),12-Labdadien-16,15-Olide-3β,19 Oxdide: a Diterpene from the aerial parts of Andrographis paniculata," Phytochemistry, 37(5):1477-1479 (1994).
Jiang Zemin, President of the People's Republic of China, Pharmaceutical Administration Law of the People's Republic of China (2001).
Jianguo Ji, "Declaration under 37 C.F.R. § 1.132" with Exhibits 1, dated Dec. 20, 2010.
Jianguo Ji, "Declaration under 37 C.F.R. § 1.132" with Exhibits 1-4, filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
Jifeng Duan, "Declaration under 37 C.F.R. § 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
Kakrani et al., "Traditional treatment of gastro-intestinal tract disorders in Kutch district, Gujarat state, India," Journal of Natural Remedies, 2/1: 71-75 (2002).
Kleipool, "Constituents of Andrographis paniculata nees," Nature, 169(4288):33-34 (1952).
Kumar et al., "Anticancer and immunomodulatory potential of DRF-3188, an analogue of andrographolide," Novel Compounds from Natural Products in the New Millenium, 205-216, (2004). (Abstract).
Kumar, et al., "Anticancer and immunomodulatory potential of DRF-3188, an analogue of andrographolide", Novel Compounds from Natural Products in the New Millenium, 205-216, 2004, abstract.
Li Wang, "Declaration under 37 C.F.R. § 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
Madav et al., "Analgesic, antipyretic and antiulcerogenic effects of andrographolide," Indian J. Pharm. Sci., 57(3):121-125 (1995).
Madav et al., "Anti-inflammatory activity of andrographolide," Fitoterapia, 67:452-458, (1996).
Mahadevan et al., "Safety of selective cyclooxygenase-2 inhibitors in inflammatory bowel disease," Am. J. Gastroenterology, 97(4): 910-4 (2002) (Abstract).
Matsuda et al., "Cell differentiation-inducing diterpenes from Andrographis paniculata Nees," Chem. Pharm. Bull., 42(6):1216-1225 (1994).
Matsuda et al., "Studies on the cell differentiation induces of Andrographis paniculata," Tennen Yuki Kagobutsu Toronkai Koen Yoshishu, 33:433-440 (1991) (Abstract).
Melchior et al., "Double-blind, placebo-controlled pilot and phase III study of activity of standardized Andrographis paniculata Herba Nees extract fixed combination (Kan jang) in the treatment of uncomplicated upper-respiratory tract infection," Phytomedicine, 7(5): 341-350 (2000).
Mishra et al., "Andrographis paniculata (Kalmegh): A Review," Pharmacognosy Reviews, 1(2):283-298 (2007).
Misra et al., "Antimalarial activity of traditional plants against erythrocytic stages of Plasmodium berghei," International Journal of Pharmacognosy, (29): 19-23 (1991).
Nazimudeen et al., "Effect of Andrographis paniculata on snake venom-induced death and its mechanism," Indian Journal of Pharmaceutical Sciences, (40):132-133 (1978).
Notice of Allowance and Fee(s) Due mailed Jul. 1, 2011, in Reissue U.S. Appl. No. 12/717,260.
Notice of Appeal under 37 C.F.R. § 41.31 and Appeal Brief Under Board Rule § 41.37, both filed Jan. 18, 2012, in U.S. Appl. No. 11/934,143.
Office Action mailed Aug. 1, 2006, in U.S. Appl. No. 11/116,678.
Office Action mailed Dec. 15, 2009, in U.S. Appl. No. 11/934,143.
Office Action mailed Jul. 7, 2008, in U.S. Appl. No. 11/934,143.
Office Action mailed Jun. 16, 2010, in U.S. Appl. No. 11/674,557.
Office Action mailed Jun. 2, 2009, in U.S. Appl. No. 11/674,557.
Office Action mailed Jun. 23, 2010, in Reissue U.S. Appl. No. 12/717,260.
Office Action mailed May 12, 2011, in U.S. Appl. No. 11/934,143.
Office Action mailed May 13, 2011, in U.S. Appl. No. 12/264,646.
Otake et al., "Screening of Indonesian plant extracts for anti-human immunodeficiency virus type 1 (HIV-1) activity," Phytotherapy Research, (9): 6-10 (1995).
Panossian et al., "Effect of Andrographis paniculata extract on progesterone in blood plasma of pregnant rats," Phytomedicine, 6(3): 157-161 (1999).
Panossian et al., "Effect of Andrographis paniculata extract on progesterone in blood plasma of pregnant rats," Phytomedicine, 6(3):157-161 (1999). (Abstract).
Panossian et al., "Effect of andrographolide and Kan Jang-fixed combination of extract SHA-10 and extract SHE-3-on proliferation of human lymphocytes, production of cytokines and immune activation markers in the whole blood cells culture," Phytomedicine, 9(7):598-605 (2002). (Abstract).
Panossian, et al., "Effect of andrographolide and Kan Jang—fixed combination of extract SHA-10 and extract SHE-3—on proliferation of human lymphocytes, production of cytokines and immune activation markers in the whole blood cells culture", Phytomedicine, 9(7):598-605, 2002, abstract.
PCT International Preliminary Report on Patentability issued Sep. 2, 2008, in International Application No. PCT/CN2007/000616.
PCT International Preliminary Report on Patentability mailed Nov. 9, 2006, in International Appication No. PCT/US2005/14288.
PCT Notification of Transmittal of the International Search Report and the Written Opinion of the International Searching Authority, mailed Sep. 13, 2006, in International Application No. PCT/US2005/008317.
PCT Notification of Transmittal of the International Search Report and the Written Opinion of the International Searching Authority, or the Declaration, mailed Dec. 9, 2005, in International Application No. PCT/US05/14288.
PCT Notification of Transmittal of the International Search Report and the Written Opinion of the International Searching Authority, or the Declaration, mailed Jan. 26, 2009, in International Application No. PCT/US2008/082022.
PCT Notification of Transmittal of the International Search Report and the Written Opinion of the International Searching Authority, or the Declaration, mailed Jun. 7, 2007, in International Application No. PCT/CN2007/000616.
Peng et al., "Modulation of Lianbizi injection (andrographolide) on some immune functions," Zhongguo Zhongyao Zazhi, 27(2):147-150 (2002) (Abstract).
Poolsup et al., "Andrographis paniculata in the symptomatic treatment of uncomplicated upper respiratory tract infection: systematic review of randomized controlled trials," J. Clin. Pharm. Ther, 29(1): 37-45 (2004).
Practical Techniques for National Qualification Examination of Professional Skills in Chinese medication, Professional Skills, Shanghai Science and Technology Press, China, p. 164 (2003).
Pramanick et al., "Andropanolide and isoandrographolide, minor diterpenoids from Andrographis paniculata: structure and X-ray crystallographic analysis," J. Nat. Prod., 69: 403-405 (2006).
Pre-IND Submission Meeting Briefing Document (Redacted) (2005).
Puri et al., "Immunostimulant agents from Andrographis Paniculata," Journal of National Products, 56(7):995-999 (1993).
Puri et al., "Immunostimulant Agents from Andrographis Paniculata," Journal of National Products, vol. 56, No. 7, pp. 995-999 (1993).
Qian et al., "A comparison of pharmacological effects between CXL extract and CXL compound prescription," Journal of Luzhou Medical School, 11(3): 189-191 (1988), Abstract only.
Rajagopal et al., "Andrographolide, a potential cancer therapeutic agent isolated from Andrographis paniculata," Journal of Experimental Therapeutics and Oncology, 3(3):147-158 (2003). (Abstract).
Rajagopal, et al., "Andrographolide, a potential cancer therapeutic agent isolated from Andrographis paniculata" , Journal of Experimental Therapeutics and Oncology, 3(3):147-158, 2003, abstract.
Rao et al., "Flavonoids and andrographolides from Andrographis paniculata," Phytochemistry, 65(16):2317-2321 (2004). (Abstract).
Reddy et al., "A flavone and an unusual 23-carbon terpenoid from Andrographis paniculata," Phytochemistry, 62:1271-1275 (2003).
Reddy et al., "A new BIS-Andrographolide ether from Andrographis paniculata Nees and evaluation of anti-HIV activity," Natural Product Research, 19(3):223-230 (2005).
Reply to Action of Feb. 21, 2007 with Exhibit A, filed May 21, 2007, in U.S. Appl. No. 11/116,678.
Reply to Communication pursuant to Article 94(3) EPC of Jul. 5, 2010 filed Jan. 14, 2011, in EP 1747008.
Reply to Final Office Action; filed Mar. 10, 2011, in Reissue U.S. Appl. No. 12/717,260.
Reply to Office Action filed Aug. 15, 2011, in U.S. Appl. No. 12/264,646.
Reply to Office Action filed Mar. 15, 2010, in U.S. Appl. No. 11/934,143.
Reply to Office Action filed Oct. 1, 2009, in U.S. Appl. No. 11/674,557.
Reply to Office Action; filed Dec. 21, 2010, in Reissue U.S. Appl. No. 12/717,260.
Reply to Office filed Jul. 21, 2011, in U.S. Appl. No. 11/934,143.
Restriction Requirement mailed Mar. 21, 2011, in U.S. Appl. No. 12/264,646.
Rutgeerts et al., "Onercept for Moderate-to-Severe Crohn's Disease: A Randomized, Double-Blind, Placebo-Controlled Trial," Clinical Gastroenterology and Hepatology, 4:888-893 (2006).
Sandborn et al., "Anti-CD3 antibody visilizumab is not effective in patients with intravenous corticosteroid-refractory ulcerative colitis," Gut, 59: 1485-1492 (2010).
Saxena et al., "Phytochemicals from Andrographis paniculata," Indian J. Chem., 42B:3159-3163 (2003).
Saxena et al., "High-performance thin-layer chromatographic analysis of heptoprotective diterpenoids from Andrographis paniculata," Phytochem Anal, 11:34-36 (2000).
See et al., "Increased tumor necrosis factor alpha (TNF-. alpha.) and natural killer cell (NK) function using an integrative approach in late stage cancers," Immunological Investigations, 31(2):137-153 (2002). (Abstract).
See, et al., "Increased tumor necrosis factor alpha (TNF-. alpha.) and natural killer cell (NK) function using an integrative approach in late stage cancers", Immunological Investigations, 31(2):137-153, 2002, abstract.
Shen et al., "Andrographolide prevents oxygen radical production by human neutrophils: possible mechanism(s) involve in its anti-inflammatory effect," British Journal of Pharmacology, 135:399-406 (2002).
Shen et al., "ent-Labdane diterpenoids from Andrographis paniculata," J. Nat. Prod., 69:319-322 (2006).
Shen et al., "Andrographolide prevents oxygen radical production by human neutrophils: possible mechanism(s) involve in its anti-inflammatory effect", British Journal of Pharmacology 135:349-405, 2002.
Singha et al., "Antimicrobial activity of Andrographis paniculata," Fitoterapia, 74:692-694 (2003).
Singha et al., "Antimicrobial activity of Andrographis paniculata," Fitoterapia, 74:692-694, 2003.
Slide presented to FDA in Jul. 2010.
Supplementary Reply Under 37 C.F.R. § 1.116, Terminal Disclaimer, and Supplemental Reissue Declaration under 37 C.F.R. § 1.175, filed Apr. 6, 2011, in Reissue U.S. Appl. No. 12/717,260.
Tang et al., "Herbal extract HMPL-004 in Active Ulcerative Colitis: A Randomized Comparison with Sustained Release Mesalamine," American Journal of Gastroenterology (2010).
Tao Wang, "Declaration under 37 C.F.R. § 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
Thamaree et al., "The effect of andrographolide on the production of proinflammatory cytokines by in vitro stimulated human blood cells," Inflammation Res., 46, Suppl. 3, S224, (1997). (Abstract).
Tharmaree, et al., "The effect of andrographolide on the production of proinflammatory cytokines by in vitro stimulated human blood cells", Inflammation Res., 46, Suppl. 3, S224, 1997, abstract.
Townsend et al., "Extracts of Chinese Herbs Inhibit IL-Ibeta- and UV-induced MMP Expression in Cultured Human Keratinocytes," FASEB Journal, 15(4): A184 (2001).
Townsend et al., "Extracts of Chinese Herbs Inhibit IL-Ibeta- and UV-induced MMP Expression in Cultured Human Keratinocytes," FASEB Journel, Mar. 2001, vol. 15, No. 4, p. A184.
Trivedi et al., "Hepatoprotective and antioxidant property of Andrographis paniculata (Nees) in BHC induced liver damage in mice," Indian J. Exp. Biol., 39(1):41-6 (2001). (Abstract).
Trivedi et al., "Hepatoprotective and antioxidant property of Andrographis paniculata (Nees) in BHC induced liver damage in mice" Indian J. Exp. Biol. 39(1):41-6, 2001, abstract.
Vedavathy et al., "Antipyretic activity of six indigenous medicinal plants of Tirumala Hills, Andhra Pradesh, India," Journal of Ethnopharmacology, 33(1-2): 193-196 (1991).
Wang et al., "A Discussion on the effect of the extraction process of Chinese traditional medicine on the quality of the resulting drug," Heilongjiang Chinese Medicine, No. 2: 45-46 (1992).
Wang et al., "Andrographolide reduces inflammation-mediated dopaminergic neurodegeneration in mesencephalic neuron-glia cultures by inhibiting microglial activation," Journal of Pharmacology and Experimental Therapeutics, 308(3):915-983 (2004) (Abstract).
Wang et al., "Chemical constituents from leaves of Andrographis paniculata," J. China Pharma. Univ., 36(5):405-407 (2005), Abstract only.
Weihan Zhang, "Declaration under 37 C.F.R. § 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
Weihan Zhang, "First Declaration under 37 C.F.R. § 1.132," dated Dec. 21, 2010.
Weihan Zhang, "First Declaration under 37 C.F.R. § 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
Weihan Zhang, "Second Declaration under 37 C.F.R. § 1.132," dated Dec. 21, 2010.
Weihan Zhang, "Second Declaration under 37 C.F.R. § 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
Weihan Zhang, Third Declaration Under 37 C.F.R § 1.132, dated Mar. 10, 2011.
William J. Sandborn, "Declaration of William J. Sandborn, M.D., under 37 C.F.R. § 1.132" with Exhibit 1, filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
Xia, "Andrographolide Attenuates Inflammation by Inhibition of NF-kB Activation Through Covalent Modification of Reduced Cysteine 62 of p501," The Journal of Immunology, 4207-4217 (2004).
Xiaoqiang Yan, "Declaration under 37 C.F.R. § 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
Xun Zhang, "Declaration under 37 C.F.R. § 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
Yao et al, "Mechanism of inhibition of HIV-1 infection in vitro by a purified extract of Prunella vulgaris," Virology, 187(1): 56-62 (1992).
Yu Cai, "Declaration under 37 C.F.R. § 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
Yuqing Wang, "Declaration under 37 C.F.R. § 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
Zhang et al., "Antihyperglycaemic and anti-oxidant properties of andrographis paniculata in normal and diabetic rats," Clinical and Experimental Pharmacology and Physiology, 27:358-363 (2000).
Zhang et al., "Effects of 14-Deoxyandrographolide and 14-Deoxy-11, 12-Didehydroandrographolide on Nitric Oxide Production in Cultured Human Endothelial Cells," Phytotherapy Research, 13:157-159 (1999).
Zhang et al., "Experimental Studies of the destructive actions of Andrographis paniculata nees on endotoxin in vitro," Chinese J. of Integrated Traditional and Western Medicine in Intensive and Critical Care, 7(4):212-214 (2000), Abstract only.
Zhang et al., "New Diterpenoids from Andrographis paniculata (Burm. f.) nees," J. of Integrative Plant Biology, 48(9): 1122-1125 (2006).
Zhang et al., "Antihyperglycaemic and anti-oxidant properties of Andrographis paniculata in normal and diabetic rats," Clinical and Experimental Pharmacology and Physiology, 27:358-363, (2000).
Zhao et al., "Determination of andrographolide, deoxyandrographolide and neoandrographolide in the Chinese herb Andrographis paniculata by micellar electrokinetic capillary chromatography," Phytochem Anal, 13: 222-227 (2002).
Zhiming Ma, "Declaration under 37 C.F.R. § 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
Zhong et al., "Three salts of labdanic acids from Andrographis paniculata (Acanthaceae)," Acta Botanica Sinica, 43:1077-1080 (2001).
Zhou et al., "Two new ent-labdane diterpenoid glycosides from the aerial parts of Andrographis paniculata," Journal of Asian Natural Products Research, 10(10):939-943 (2008).

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110142944A1 (en) * 2006-02-28 2011-06-16 Hutchison Medipharma Enterprises Limited, Offshore Group Chambers Andrographis extract formulations
US20090117210A1 (en) * 2007-11-02 2009-05-07 Hutchison Medipharma Enterprises Limited Andrographis paniculata extract
US8557302B2 (en) 2007-11-02 2013-10-15 Nutrition Science Partners Limited Andrographis paniculata extract
US8557308B2 (en) 2007-11-02 2013-10-15 Nutrition Science Partners Limited Andrographis paniculata extract

Also Published As

Publication number Publication date
KR20150047645A (en) 2015-05-04
CA2564637A1 (en) 2005-11-10
WO2005104722A3 (en) 2006-03-02
KR101531116B1 (en) 2015-06-23
KR20070033982A (en) 2007-03-27
PT1747008E (en) 2015-03-31
WO2005104722A2 (en) 2005-11-10
US7341748B2 (en) 2008-03-11
KR101536892B1 (en) 2015-07-14
RU2383353C2 (en) 2010-03-10
KR20130012979A (en) 2013-02-05
AU2005237550A1 (en) 2005-11-10
EP1747008A2 (en) 2007-01-31
TW200538144A (en) 2005-12-01
AU2005237550B2 (en) 2010-09-23
RU2006141834A (en) 2008-06-10
HUE025117T2 (en) 2016-02-29
US20060246156A1 (en) 2006-11-02
PL1747008T3 (en) 2015-10-30
CA2564637C (en) 2013-09-10
USRE42718E1 (en) 2011-09-20
JP2007535542A (en) 2007-12-06
EP1747008B1 (en) 2015-01-14
KR101534844B1 (en) 2015-07-07
ES2534594T3 (en) 2015-04-24
JP5221128B2 (en) 2013-06-26
DK1747008T3 (en) 2015-03-30
TWI373340B (en) 2012-10-01
EP1747008A4 (en) 2009-04-22

Similar Documents

Publication Publication Date Title
USRE43423E1 (en) Crude extracts from Andrographis paniculata
US7625945B2 (en) Andrographolide and analogues as inhibitors of TNFα and IL-1β expression
US8557302B2 (en) Andrographis paniculata extract
US20050124684A1 (en) 5-(hydroxymethyl) furfural and derivatives as inhibitors of TNFalpha and IL-1beta production
JP2016523849A (en) Combination therapy for prostate cancer using plant composition and docetaxel
US20060110467A1 (en) Cancer chemotherapy
US20050148616A1 (en) Inhibitor of TNF-alpha and IL-1beta production
KR100889169B1 (en) Antagonistic pharmaceutical composition for neurokinin-1 receptor
KR0143719B1 (en) Polyoxypregnane Glycosides with Multi-drug Resistance Regulation of Cancer Cells Extracted from Baek Ha Shou
KR20090087684A (en) Composition for preventing or treating a disease mediated by overexpression of heat shock protein 27
KR20200029702A (en) Pharmaceutical composition including abeliophyllum distichum extract for preventing or treating liver injury
KR20220041870A (en) bioactive phytochemicals
KR20160065336A (en) Composition comprising petatewalid B for preventing or treating allergy

Legal Events

Date Code Title Description
FEPP Fee payment procedure

Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

CC Certificate of correction
CC Certificate of correction
AS Assignment

Owner name: NUTRITION SCIENCE PARTNERS LIMITED, HONG KONG

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:HUTCHISON MEDIPHARMA ENTERPRISES LIMITED;REEL/FRAME:030658/0421

Effective date: 20130529

FPAY Fee payment

Year of fee payment: 8

MAFP Maintenance fee payment

Free format text: PAYMENT OF MAINTENANCE FEE, 12TH YEAR, LARGE ENTITY (ORIGINAL EVENT CODE: M1553); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

Year of fee payment: 12