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Publication numberUSRE42718 E1
Publication typeGrant
Application numberUS 12/717,260
Publication dateSep 20, 2011
Filing dateMar 4, 2010
Priority dateApr 28, 2004
Also published asCA2564637A1, CA2564637C, EP1747008A2, EP1747008A4, EP1747008B1, US7341748, US20060246156, USRE43423, WO2005104722A2, WO2005104722A3
Publication number12717260, 717260, US RE42718 E1, US RE42718E1, US-E1-RE42718, USRE42718 E1, USRE42718E1
InventorsXiaoqiang Yan, Tao Wang, Zhiming Ma, Weihan Zhang, Jifeng Duan, Yu Cai
Original AssigneeHutchison Medipharma Enterprises Limited
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Crude extracts from andrographis paniculata
US RE42718 E1
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.
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Claims(13)
1. A method of treating an inflammatory bowel disease in a subject in recognized need thereof, comprising administering to the subject an effective amount of an extract of Andrographispaniculata, wherein the extract contains 2-20% by weight andrographolide, 1-6% by weight 14-deoxy-andrographolide, 1-12 1.0-7% 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 1-5% by weight 14-deoxy-andrographolide, 1.0-7-9% 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 1-5% by weight 14-deoxy-andrographolide, 1.0-7-9% 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. A method of treating an inflammatory bowel disease comprising administering to a patient in recognized need of such treatment an effective amount for treating of 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.
9. A method of treating an inflammatory bowel disease comprising administering to a patient in recognized need of such treatment an effective amount for treating of 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.
10. The method of claim 8 wherein said inflammatory bowel disease is Crohn's disease.
11. The method of claim 8 wherein said inflammatory bowel disease is ulcerative colitis.
12. The method of claim 9 wherein said inflammatory bowel disease is Crohn's disease.
13. The method of claim 9 wherein said inflammatory bowel disease is ulcerative colitis.
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.

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 Annu 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 IL-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 Hepatobiliary 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/dermatomyositis, 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-1β, treating a TNFα related-disorder, and treating an IL-1β-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-1β 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 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. 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 1105 cells/ml and seeded in a 96-well plate (1104 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 (CalBiochem.) 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.

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US6358526Aug 16, 2000Mar 19, 2002Rexall SundownMethod of making tablets and tablet compositions produced therefrom
US7341748Apr 27, 2005Mar 11, 2008Hutchison Medipharma Enterprises LimitedCrude extracts from Andrographis paniculata
US7625945Mar 11, 2005Dec 1, 2009Hutchison MediPharma Enterprises Ltd.Andrographolide and analogues as inhibitors of TNFα and IL-1β expression
US20020068098Aug 1, 2001Jun 6, 2002Ashni Naturaceuticals, Inc.Combinations of diterpene triepoxide lactones and ditepene lactones or triterpenes for synergistic inhibition of cyclooxygenase-2
US20030059471Nov 29, 2001Mar 27, 2003Compton Bruce JonOral delivery formulation
US20030091517Nov 8, 2002May 15, 2003Mahidol UniversityAndrographis paniculata gel as an adjunct in the treatment of periodontitis
US20030101076Sep 19, 2002May 29, 2003Zaleski John R.System for supporting clinical decision making through the modeling of acquired patient medical information
US20030104076Nov 7, 2002Jun 5, 2003Wilhelm BerkulinProcess for preparing dry extracts
US20040053858Jul 23, 2001Mar 18, 2004Berg Kurt FrimannMethod of treating symptoms of common cold, allergic rhinitis and infections relating to the respiratory tract
US20040151792Oct 20, 2003Aug 5, 2004Tripp Matthew L.Compositions that treat or inhibit pathological conditions associated with inflammatory response
US20050215628Mar 11, 2005Sep 29, 2005Hutchison Medipharma Ltd.Andrographolide and analogues as inhibitors of TNFalpha and IL-1beta expression
US20060246156Apr 27, 2005Nov 2, 2006Hutchinson Medipharma Enterprises LimitedCrude extracts from andrographis paniculata
US20070202164Feb 13, 2007Aug 30, 2007Hutchison Medipharma Enterprises LimitedAndrographis Extract Formulations
US20070218114Jun 13, 2005Sep 20, 2007Passionfor Life Healthcare LimitedSoluble Strip for Oral or Topical Administration
US20090117209Nov 2, 2007May 7, 2009Hutchison Medipharma Enterprises LimitedAndrographis paniculata extract
US20090117210Nov 4, 2008May 7, 2009Hutchison Medipharma Enterprises LimitedAndrographis paniculata extract
CN1042077AJul 29, 1989May 16, 1990郭如明Alkali-water process for creat
CN1488376AMay 9, 2003Apr 14, 2004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
CN1626076ADec 11, 2003Jun 15, 2005天津天士力制药股份有限公司Andrographolide drop pills and preparation method
CN1628764AAug 19, 2004Jun 22, 2005贵阳云岩西创药物科技开发有限公司Creat formulation and its preparation process
JP2000034233A Title not available
JP2001058969A Title not available
JP2004075638A Title not available
KR20050067951A Title not available
WO2005104722A2Apr 26, 2005Nov 10, 2005Hutchison Medipharma Entpr LtdCrude extracts from andrographis paniculata
WO2007098686A1Feb 27, 2007Sep 7, 2007Hutchison Medipharma Entpr LtdAndrographis extract formulations
WO2009059158A1Oct 31, 2008May 7, 2009Hutchison Medipharma Entpr LtdAndrographis paniculata extract
Non-Patent Citations
Reference
1Achike 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).
2Akbarsha et al., "Antifertility effect of Andrographis paniculata (nees) in male albino rat," Indian Journal of Experimental Biology, 28:421-426 (1990).
3Amendment and Reply Under 37 C.F.R. 1.114 filed Sep. 18, 2009, in U.S. Appl. No. 11/934,143.
4Amendment and Reply under 37 U.S.C. 1.114, in U.S. Appl. No. 11/934,143, filed Dec. 15, 2010.
5Amendment in Reply to Action of Aug. 1, 2006 filed Dec. 1, 2006, in U.S. Appl. No. 11/116,678.
6Amendment 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.
7Andrographis Paniculata Tablets, The Pharmacopoeia of People's Republic of China (2000 ed.), Vol. I, p. 541 (2000).
8Andrographis Paniculata Tablets, The Pharmacopoeia of People's Republic of China (2005 ed.), Vol. I, pp. 549-550 (2005).
9Assche 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).
10Balmain et al., "Minor Diterpenoid Constituents of Andrographis paniculata Nees," J. Chem. Soc. Perkin. Trans. I (1973): 1247-1251.
11Basak 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).
12Burgos et al., "Testicular toxicity assessment of Andrographis paniculata dried extract in rats," J. Ethnopharmacol., 58(3): 219-224 (1997).
13Calabrese et al., "A Phase I Trial of Andrographolide in HIV Positive Patients and Normal Volunteers," Phytother. Res., 14:333-338 (2000).
14Chang et al., "Dehydroandrographolide succinic acid monoester as an inhibitor against the human immunodeficiency virus," Proc. Soc. Exp. Biol. Med., 197(1): 59-66 (1991).
15Chen et al. , "Studies on flavonoids of Andrographis paniculata," China J. Chinese Materia Medica., 31(5):391-395 (2006).
16Chen et al., "Nine new ent-labdane diterpenoids from the aerial parts of Andrographis paniculata," Helvetica Chimica Acta, 89:2654-2664 (2006).
17Chen et al., "Studies on diterpenoids from Andrographis paniculata," China J. Chinese Materia Medica., 31(19):1594-1597 (2006).
18Communication pursuant to Rule 114(2) EPC in EP1996165, dated Apr. 29, 2010, enclosing Third Party Observations.
19Coon 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).
20Deng et al., Chinese Pharm. Bull., 17:195-198 (1982).
21 *English translation of JP 2000034233 A-2000.
22 *English translation of JP 2000034233 A—2000.
23Ex parte Subramanyam (BPAI, Mar. 29, 2010).
24Feagan et al., "Omega-3 Free Fatty Acids for theMaintenance of Remission in Crohn Disease," JAMA, 299(14):1690-1697 (2008).
25Final Office Action mailed Feb. 21, 2007, in U.S. Appl. No. 11/116,678.
26Final Office Action mailed Jan. 4, 2010, in U.S. Appl. No. 11/674,557.
27Final Office Action mailed Jun. 16, 2010, in U.S. Appl. No. 11/934,143.
28Final Office Action mailed Mar. 20, 2009, in U.S. Appl. No. 11/934,143.
29Fujita 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).
30George 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).
31Ghosh et al., "Isolation of Andrographis paniculata leaf protein with antifungal property," Acto. Phytopathologica et Entomologica Hungarica, 39(4):377-381 (2004).
32Guidance 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.
33Gupta 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).
34Gupta et al., "Antisecretory (antidiarrhoeal) activity of Indian medicinal plants against Escherichia coli enterotoxin-induced secretion in rabbit and guinea pig ileal loop models," Inl. J, Pharmacog., 31(3):198-204 (1993).
35Gupta et al., "Flavonoid glycoside of Andrographis paniculata," Indian J. Chem., 35 B:512-513 (1996).
36Gupta et al., "Flavonoids of Andrographis paniculata," Phytochemistry, 22(1):314-315 (1983).
37Habtemariam, "Andrographolide inhibits the tumour necrosis Factor-alpha-induced upregulation of ICAM-1 expression and endothelial-monocyte adhesion," Phytotherapy Research, 12:37-40 (1998).
38Habtemariam, "Natural Inhibitors of Tumor Necrosis Factor-alpha Production, Secretion and Function," Planta Medica, 66:303-313 (2000).
39Habtemariam, "Andrographolide inhibits the tumour necrosis Factor-α-induced upregulation of ICAM-1 expression and endothelial-monocyte adhesion," Phytotherapy Research, 12:37-40 (1998).
40Habtemariam, "Natural Inhibitors of Tumor Necrosis Factor-α Production, Secretion and Function," Planta Medica, 66:303-313 (2000).
41 *Hasko (Immunology (2001), vol. 103, pp. 473-478).
42Herba Andrographis, World Health Organization (WHO) monographs on selected medicinal plants, Vol. 2. pp. 12-24 (2002).
43Herbs, Andrographis paniculata's wide range of medicinal Powers, (2002).
44Jalal et al., "Formation of three new Flavones by differentiating callus cultures of Andrographis paniculata," Phytochemistry, 18:149-151 (1979).
45Jantan 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).
46Jantan 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).
47Jianguo Ji, "Declaration under 37 C.F.R. 1.132" with Exhibits 1, dated Dec. 20, 2010.
48Jianguo 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.
49Jifeng Duan, "Declaration under 37 C.F.R. 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
50Kakrani et al., "Traditional treatment of gastro-intestinal tract disorders in Kutch district, Gujarat state, India," Journal of Natural Remedies, 2/1: 71-75 (2002).
51Kleipool, "Constituents of Andrographis paniculata nees," Nature, 169(4288):33-34 (1952).
52Kumar et al., "Anticancer and immunomodulatory potential of DRF-3188, an analogue of andrographolide," Novel Compounds from Natural Products in ihe New Millenium, 205-216, (2004). (Abstract).
53Li Wang, "Declaration under 37 C.F.R. 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
54Madav et al., "Analgesic, antipyretic and antiulcerogenic effects of andrographolide," Indian J. Pharm. Sci., 57(3):121-125 (1995).
55Madav et al., "Anti-inflammatory activity of andrographolide," Fitoterapia, 67:452-458, (1996).
56Mahadevan et al., "Safety of selective cyclooxygenase-2 inhibitors in inflammatory bowel disease," Am. J. Gastroenterology, 97(4): 910-4 (2002) (Abstract).
57Matsuda et al., "Cell differentiation-inducing diterpenes from Andrographis paniculata Nees," Chem. Pharm. Bull., 42(6):1216-1225 (1994).
58Matsuda et al., "Studies on the cell differentiation induces of Andrographis paniculata," Tennen Yuki Kagobutsu Toronkai Koen Yoshishu, 33:433-440 (1991) (Abstract).
59Mishra et al., "Andrographis paniculata (Kalmegh): A Review," Pharmacognosy Reviews, 1(2):283-298 (2007).
60Misra et al., "Antimalarial activity of traditional plants against erythrocytic stages of Plasmodium berghei," International Journal of Pharmacognosy, (29): 19-23 (1991).
61Nazimudeen et al., "Effect of Andrographis paniculata on snake venom-induced death and its mechanism," Indian Journal of Pharmaceutical Sciences, (40):132-133 (1978).
62Office Action mailed Aug. 1, 2006, in U.S. Appl. No. 11/116,678.
63Office Action mailed Dec. 15, 2009, in U.S. Appl. No. 11/934,143.
64Office Action mailed Jul. 7, 2008, in U.S. Appl. No. 11/934,143.
65Office Action mailed Jun. 16, 2010, in U.S. Appl. No. 11/674,557.
66Office Action mailed Jun. 2, 2009, in U.S. Appl. No. 11/674,557.
67Otake et al., "Screening of Indonesian plant extracts for anti-human immunodeficiency virus type 1 (HIV-1) activity," Phytotherapy Research, (9): 6-10 (1995).
68Panossian et al., "Effect of Andrographis paniculata extract on progesterone in blood plasma of pregnant rats," Phytomedicine, 6(3):157-161 (1999). (Abstract).
69Panossian 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).
70Panossian 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).
71PCT International Preliminary Report on Patentability issued Sep. 2, 2008, in International Application No. PCT/CN2007/000616.
72PCT International Preliminary Report on Patentability mailed Nov. 9, 2006, in International Application No. PCT/US2005/14288.
73PCT 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.
74PCT 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.
75PCT 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.
76PCT 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.
77Peng et al., "Modulation of Lianbizi injection (andrographolide) on some immune functions," Zhongguo Zhongyao Zazhi, 27(2):147-150 (2002) (Abstract).
78Poolsup 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).
79Practical Techniques for National Qualification Examination of Professional Skills in Chinese medication, Professional Skills, Shanghai Science and Technology Press, China, p. 164 (2003).
80Pramanick et al., "Andropanolide and isoandrographolide, minor diterpenoids from Andrographis paniculata: structure and X-ray crystallographic analysis," J. Nat. Prod., 69: 403-405 (2006).
81Pre-IND Submission Meeting Briefing Document (Redacted) (2005).
82Puri et al., "Immunostimulant agents from Andrographis Paniculata," Journal of National Products, 56(7):995-999 (1993).
83Qian et al., "A comparison of pharmacological effects between CXL extract and CXL compound prescription," Journal of Luzhou Medical School, 11(3): 189-191 (1988).
84Rajagopal et al., "Andrographolide, a potential cancer therapeutic agent isolated from Andrographis paniculata," Journal of Experimental Therapeutics and Oncology, 3(3):147-158 (2003). (Abstract).
85Rao et al., "Flavonoids and andrographolides from Andrographis paniculata," Phytochemistry, 65(16):2317-2321 (2004). (Abstract).
86Reddy et al., "A flavone and an unusual 23-carbon terpenoid from Andrographis paniculata," Phytochemistry, 62:1271-1275 (2003).
87Reddy 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).
88Reply to Action of Feb. 21, 2007 with Exhibit A, filed May 21, 2007, in U.S. Appl. No. 11/116,678.
89Reply to Office Action filed Mar. 15, 2010, in U.S. Appl. No. 11/934,143.
90Reply to Office Action filed Oct. 1, 2009, in U.S. Appl. No. 11/674,557.
91Rutgeerts 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).
92Sandborn et al., "Anti-CD3 antibody visilizumab is not effective in patients with intravenous corticosteroid-refractory ulcerative colitis," Gut, 59: 1485-1492 (2010).
93Saxena et al., "Phytochemicals from Andrographis paniculata," Indian J. Chem., 42B:3159-3163 (2003).
94See 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).
95Shen 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).
96Shen et al., "ent-Labdane diterpenoids from Andrographis paniculata," J. Nat. Prod., 69:319-322 (2006).
97Singha at al., "Antimicrobial activity of Andrographis paniculata," Fitoterapia, 74:692-694 (2003).
98Slide presented to FDA in Jul. 2010.
99Tang et al., "Herbal extract HMPL-004 in Active Ulcerative Colitis: A Randomized Comparison with Sustained Release Mesalamine," American Journal of Gastroenterology (2010).
100Tao Wang, "Declaration under 37 C.F.R. 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
101Thamaree 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).
102Townsend et al., "Extracts of Chinese Herbs Inhibit IL-Ibeta- and UV-induced MMP Expression in Cultured Human Keratinocytes," FASEB Journal, 15(4): A184 (2001).
103Trivedi 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).
104Vedavathy et al., "Antipyretic activity of six indigenous medicinal plants of Tirumala Hills, Andhra Pradesh, India," Journal of Ethnopharmacology, 33(1-2): 193-196 (1991).
105Wang 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).
106Wang 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).
107Wang et al., "Chemical constituents from leaves of Andrographis paniculata," J. China Pharma. Univ., 36(5):405-407 (2005).
108Weihan Zhang, "Declaration under 37 C.F.R. 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
109Weihan Zhang, "First Declaration under 37 C.F.R. 1.132," dated Dec. 21, 2010.
110Weihan Zhang, "First Declaration under 37 C.F.R. 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
111Weihan Zhang, "Second Declaration under 37 C.F.R. 1.132," dated Dec. 21, 2010.
112Weihan Zhang, "Second Declaration under 37 C.F.R. 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
113William 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.
114Xia, "Andrographolide Attenuates Inflammation by Inhibition of NF-kappaB Activation Through Covalent Modification of Reduced Cysteine 62 of p501," The Journal of Immunology, 4207-4217 (2004).
115Xia, "Andrographolide Attenuates Inflammation by Inhibition of NF-κB Activation Through Covalent Modification of Reduced Cysteine 62 of p501," The Journal of Immunology, 4207-4217 (2004).
116Xiaoqiang Yan, "Declaration under 37 C.F.R. 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
117Xun Zhang, "Declaration under 37 C.F.R. 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
118Yao et al., "Mechanism of inhibition of HIV-1 infection in vitro by a purified extract of Prunella vulgaris," Virology, 187(1): 56-62 (1992).
119Yu Cai, "Declaration under 37 C.F.R. 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
120Yuqing Wang, "Declaration under 37 C.F.R. 1.132," filed on Dec. 15, 2010, in U.S. Application No. 11/934,143.
121Zhang 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).
122Zhang 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).
123Zhang 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).
124Zhang et al., "New Diterpenoids from Andrographis paniculata (Burm. f.) nees," J. of Integrative Plant Biology, 48(9): 1122-1125 (2006).
125Zhiming Ma, "Declaration under 37 C.F.R. 1.132," filed on Dec. 15, 2010, in U.S. Appl. No. 11/934,143.
126Zhong et al., "Three salts of labdanic acids from Andrographis paniculata (Acanthaceae)," Acta Botanica Sinica, 43:1077-1080 (2001).
127Zhou 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).
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US8557302Nov 4, 2008Oct 15, 2013Nutrition Science Partners LimitedAndrographis paniculata extract
US8557308Sep 11, 2012Oct 15, 2013Nutrition Science Partners LimitedAndrographis paniculata extract
Classifications
U.S. Classification424/725
International ClassificationA61K36/00, A61K36/19
Cooperative ClassificationA61K31/365, A61K36/19
European ClassificationA61K31/365, A61K36/19
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