(19) United States
`(12) Patent Application Publication (10) Pub. No.: US 2006/0193962 A1
`
`Kamiya et al.
`(43) Pub. Date:
`Aug. 31, 2006
`
`US 20060193962A1
`
`(54) PREVENTIVE 0R REMEDY FOR
`ARTHRITIS
`
`(30)
`
`Foreign Application Priority Data
`
`(75)
`
`Inventors: Toshikazu Kamiya, lbaraki (JP);
`Ryusuke Nakagiri, Chapel Hill, NC
`(US)
`
`Correspondence Address:
`FITZPATRICK CELLA HARPER & SCINTO
`30 ROCKEFELLER PLAZA
`
`NEW YORK, NY 10112 (US)
`
`(73) Assignee: Kyowa Hakko Kogyo Co., Ltd., Tokyo
`(JP)
`
`(21) Appl. No.:
`
`10/552,526
`
`(22) PCT Filed;
`
`Apr. 9, 2004
`
`(86) PCT No.:
`
`PCT/JP04/05115
`
`Apr. 11, 2003
`
`(JP) ...................................... 2003-107405
`_
`_
`_
`_
`Publication Class1ficat10n
`
`(51)
`
`Int. Cl.
`A23L 1/212
`(2006.01)
`(52) US. Cl.
`.............................................................. 426/615
`(57)
`ABSTRACT
`An object of the present invention is to provide a preventing
`agent or a treating agent for arthritis or to provide foods and
`drinks, additives for foods and drinks, feeds or additives for
`feeds for prevention or treatment of arthritls.
`In order to achieve the above object, the present invention
`provides a preventing or treating agent for arthritis or foods
`and drinks, additives for foods and drinks, feeds or additives
`for feeds for prevention or treatment of arthritis comprising
`plant belonging to the genus Hydrangea or an extract of the
`plant and amino sugar or a salt thereof and/or glycosami-
`noglycan or a salt thereof as active ingredients.
`
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`US 2006/0193962 A1
`
`Aug. 31, 2006
`
`PREVENTIVE OR REMEDY FOR ARTHRITIS
`
`TECHNICAL FIELD
`
`[0001] The present invention relates to an agent for pre-
`venting or treating arthritis and to foods and drinks, addi-
`tives for foods and drinks, feeds and additives for feed for
`prevention or treatment of arthritis.
`
`BACKGROUND ART
`
`[0002] Hydrangea macrophylla Seringe var. Thunbergii
`Makino belonging to the genus Hydrangea is an allied
`species of hydrangea and said to have been made through
`breeding of Hydrangea macrophylla SER var. acuminala in
`the Edo era. Hydrangeae Dulcis Folium is prepared by
`fermentation of the harvested leaves and branch ends of
`
`Hydrangea macrophylla Seringe var. Zhunbergii Makino,
`followed by drying.
`
`[0003] Hydrangeae Dulcis Folium or its extract has long
`been used as a corrective (sweetener) in pills or as a raw
`material for buccal refrigerants. The aqueous extract of
`Hydrangeae Dulcis Folium has been used as a sweetener in
`the form of liquid or powder. The sweetening component is
`phyllodulcin.
`
`[0004] Hydrangeae Dulcis Folium has been known to have
`an anti-coccidium activity, anti-fungal activity, anti-ulcer
`activity, anti-allergic activity, hypercholesterolemia-sup-
`pressing activity, anti-periodontal bacteria activity, anti-
`oxidative activity, and the like (Abstracts of Papers pre-
`sented at the 2nd Symposium on Medicines and Foods, p.
`85, 1999). The extract of Hydrangeae Dulcis Folium is
`known to have a cholagogic effect (Yakugaku Zasshi (Jour-
`nal of Pharmaceutical Society of Japan), vol. 114, no. 6,
`401-413, 1994). In addition,
`the extract of Hydrangeae
`Dulcis Folium is also known to show in vitro the effect of
`
`inhibiting lipid peroxidation in liver microsomes (Natural
`Medicines, 1995, vol. 49, no. 1, 84-87).
`
`[0005] Meanwhile, plant belonging to the genus Hydran-
`gea or an extract of the plant has been known to have a
`preventing or treating effect for arthritis (WO 02/102,396).
`It has been also known that chondroitin sulfate, glu-
`cosamine, and the like, which are constituting components
`of cartilage have a treating effect for arthritis (Japanese
`Patent No. 2,971,579).
`
`[0006] However, no composition comprising a combina-
`tion of plant belonging to the genus Hydrangea or an extract
`of the plant and amino sugar or a salt
`thereof and/or
`glycosaminoglycan or a salt thereof has been known and it
`has not been known that the composition shows a synergistic
`preventing or treating effect for arthritis.
`
`DISCLOSURE OF THE INVENTION
`
`[0007] An object of the present invention is to provide a
`preventing agent or a treating agent for arthritis or to provide
`foods and drinks, additives for foods and drinks, feeds or
`additives for feeds for prevention or treatment of arthritis.
`
`[0008] The present invention relates to the following (1) to
`(27).
`
`(1) A preventing or treating agent for arthritis
`[0009]
`which comprises plant belonging to the genus Hydrangea or
`
`an extract of the plant and amino sugar or a salt thereof
`and/or glycosaminoglycan or a salt thereof as active ingre-
`dients.
`
`(2) The preventing or treating agent for arthritis
`[0010]
`according to (1), wherein the plant belonging to the genus
`Hydrangea is Hydrangea macrophylla Seringe var. Thun—
`bergii Makino.
`
`(3) The preventing or treating agent for arthritis
`[0011]
`according to (2), wherein the plant of Hydrangea macro—
`phylla Seringe var. Thunbergii Makino is Hydrangeae Dul-
`cis Folium.
`
`(4) The preventing or treating agent for arthritis
`[0012]
`according to any of (1) to (3), wherein the amino sugar is
`glucosamine or a salt thereof.
`
`(5) The preventing or treating agent for arthritis
`[0013]
`according to any of (1) to (4), wherein the glycosaminogly-
`can is chondroitin sulfate or a salt thereof.
`
`(6) A food and drink or an additive for foods and
`[0014]
`drinks comprising plant belonging to the genus Hydrangea
`or an extract of the plant and amino sugar or a salt thereof
`and/or glycosaminoglycan or a salt thereof.
`
`(7) The food and drink or the additive for foods and
`[0015]
`drinks according to (6), wherein it is used for prevention or
`treatment of arthritis.
`
`(8) The food and drink or the additive for foods and
`[0016]
`drinks according to (6) or (7), wherein the plant belonging
`to the genus Hydrangea is Hydrangea macrophylla Seringe
`var. Thunbergii Makino.
`
`(9) The food and drink or the additive for foods and
`[0017]
`drinks according to (8), wherein the plant of Hydrangea
`macrophylla Seringe var. Thunbergii Makino is Hydrangeae
`Dulcis Folium.
`
`(10) The food and drink or the additive for foods
`[0018]
`and drinks according to any of (6) to (9), wherein the amino
`sugar is glucosamine or a salt thereof.
`
`(11) The food and drink or the additive for foods
`[0019]
`and drinks according to any of (6) to (10), wherein the
`glycosaminoglycan is chondroitin sulfate or a salt thereof.
`
`(12) A Feed or an additive for feeds comprising
`[0020]
`plant belonging to the genus Hydrangea or an extract of the
`plant and amino sugar or a salt thereof and/or glycosami-
`noglycan or a salt thereof.
`
`(13) The feed or the additive for feeds according to
`[0021]
`(12), which is used for prevention or treatment of arthritis.
`
`(14) The feed or the additive for feeds according to
`[0022]
`(12) or (13), wherein the plant belonging to the genus
`Hydrangea is Hydrangea macrophylla Seringe var. Thun—
`bergii Makino.
`
`(15) The feed or the additive for feeds according to
`[0023]
`(14), wherein the plant of Hydrangea macrophylla Seringe
`var. Thunbergii Makino is Hydrangeae Dulcis Folium.
`
`(16) The feed or the additive for feeds according to
`[0024]
`any of (12) to (15), wherein the amino sugar is glucosamine
`or a salt thereof.
`
`(17) The feed or the additive for feeds according to
`[0025]
`any of (12) to (16), wherein the glycosaminoglycan is
`chondroitin sulfate or a salt thereof.
`
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`US 2006/0193962 A1
`
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`
`(18) A preventing or treating method for arthritis,
`[0026]
`which comprises administering plant belonging to the genus
`Hydrangea or an extract of the plant and amino sugar or a
`salt thereof and/or glycosaminoglycan or a salt thereof.
`
`(19) The preventing or treating method for arthritis
`[0027]
`according to (18), wherein the plant belonging to the genus
`Hydrangea is Hydrangea macrophylla Seringe var. Thun—
`bergii Makino.
`
`(20) The preventing or treating method for arthritis
`[0028]
`according to (19), wherein the plant of Hydrangea macro—
`phylla Seringe var. Thunbergii Makino is Hydrangeae Dul-
`cis Folium.
`
`(21) The preventing or treating method for arthritis
`[0029]
`according to any of (18) to (20), wherein the amino sugar is
`glucosamine or a salt thereof.
`
`(22) The preventing or treating method for arthritis
`[0030]
`according to any of (18) to (21), wherein the glycosami-
`noglycan is chondroitin sulfate or a salt thereof.
`
`(23) Use of plant belonging to the genus Hydran-
`[0031]
`gea or an extract of the plant and amino sugar or a salt
`thereof and/or glycosaminoglycan or a salt thereof for the
`manufacture of a preventing or treating agent for arthritis.
`
`(24) Use of plant belonging to the genus Hydran-
`[0032]
`gea or an extract of the plant and amino sugar or a salt
`thereof and/or glycosaminoglycan or a salt thereof for the
`manufacture of a food and drink or an additive for foods and
`drinks.
`
`(25) Use of plant belonging to the genus Hydran-
`[0033]
`gea or an extract of the plant and amino sugar or a salt
`thereof and/or glycosaminoglycan or a salt thereof for the
`manufacture of a food and drink or an additive for foods and
`
`drinks used for prevention or treatment of arthritis.
`
`(26) Use of plant belonging to the genus Hydran-
`[0034]
`gea or an extract of the plant and amino sugar or a salt
`thereof and/or glycosaminoglycan or a salt thereof for the
`manufacture of a feed or an additive for feeds.
`
`(27) Use of plant belonging to the genus Hydran-
`[0035]
`gea or an extract of the plant and amino sugar or a salt
`thereof and/or glycosaminoglycan or a salt thereof for the
`manufacture of a feed or an additive for feeds used for
`
`prevention or treatment of arthritis.
`
`[0036] Examples of the plants belonging to the genus
`Hydrangea are Hydrangea macrophylla Seringe, Hydran—
`gea macrophylla Seringe var. otaksa Makino, Hydrangea
`macrophylla Seringe subsp. serrala Makino var. japonica
`Makino, Hydrangea macrophylla Seringe var. acuminala,
`Hydrangea macrophylla Seringe var. Thunbergii Makino,
`Hydrangea scandens Seringe, Hydrangea hirla Sieb. et
`Zucc., Hydrangea involucrala Sieb., Hydrangea sikokiana
`Maxim., Hydrangea paniculala Sieb., Hydrangea peliolaris
`Sieb. et Zucc., Hydrangea macrophylla Seringe subsp. ser-
`rala Makino var. amoena Makino, Hydrangea macrophylla
`Seringe subsp. serrala Makino var. anguslala Makino, and
`the like. Among them, Hydrangea macrophylla Seringe var.
`Thunbergii Makino is preferably used.
`
`[0037] With regard to the plant belonging to the genus
`Hydrangea, any of, for example, wild plant, plant obtained
`
`by cultivation, plant obtained by tissue culture, and the like
`may be used, so far as it is the plant belonging to the genus
`Hydrangea.
`
`[0038] Examples of the plant are the parts such as leaves,
`flowers, branches, stems, fruits, roots, seeds, cultured cells,
`organs or callus and the like. It is also possible to use various
`treated matters prepared by physical, chemical or biological
`treatment of those parts.
`
`[0039] The physical or chemical treatment includes drying
`such as sun-drying and air-drying as well as freeze-drying
`treatment, pulverizing treatment, extracting treatment. The
`physically or chemically treated matters include dried mat-
`ters, freeze-dried matters, pulverized matters, extracted mat-
`ters, and the like.
`
`includes fermentation
`treatment
`[0040] The biological
`treatment, and the like. The biologically treated matters
`include fermented matters, and the like.
`
`[0041] When Hydrangea macrophylla Seringe var. Thun-
`bergii Makino is used as a plant belonging to the genus
`Hydrangea for example, Hydrangeae Dulcis Folium which
`is prepared by a drying treatment ofHydrangea macrophylla
`Seringe var. Thunbergii Makino after a fermenting treatment
`is preferably used.
`
`the plant belonging to the genus
`[0042] Hereinafter,
`Hydrangea will be called the plant of the present invention.
`
`[0043] Examples of the extract of the plant according to
`the present invention are substances which are obtained by
`methods for extracting the sub stances having a preventive or
`therapeutic effect for arthritis from the plant, such as extrac-
`tion with various solvent and extraction with supercritical
`fluid from the plant.
`
`[0044] With regard to the solvent used for extraction with
`solvent, any of, for example, aqueous medium and organic
`solvent may be used so far as it is a solvent which can extract
`a substance having a preventive or therapeutic effect for
`arthritis (hereinafter, may also be referred to as active
`ingredient). The solvent may be used alone or as a mixed
`solvent where two or more are combined.
`
`[0045] With regard to an aqueous medium, water, aqueous
`solution of inorganic salt, buffer, and the like may be listed
`and water is preferred.
`
`[0046] Examples of water are tap water, distilled water,
`deionized water, pure water, and the like.
`
`[0047] Examples of the buffer are a phosphate buffer, a
`citrate buffer, and the like.
`
`[0048] Examples of an inorganic salt for the aqueous
`solution of inorganic salt are sodium chloride, potassium
`chloride, calcium chloride, and the like.
`
`[0049] With regard to the organic solvent, any solvent may
`be used so far as active ingredients can be extracted and its
`examples are monohydric aliphatic alcohol such as metha-
`nol, ethanol, 1-propanol, 2-propanol, 1-butanol and 2-bu-
`tanol; dihydric aliphatic alcohol such as ethylene glycol and
`propylene glycol; trihydric aliphatic alcohol such as glyc-
`erol; alkyl acetate such as methyl acetate and ethyl acetate;
`aliphatic ketone such as acetone and ethyl methyl ketone;
`aliphatic ether such as dimethyl ether and diethyl ether;
`aliphatic hydrocarbon such as hexane, heptane and petro-
`
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`
`leum ether; alicyclic hydrocarbon such as cyclohexane;
`aromatic hydrocarbon such as toluene and benzene; halo-
`genated aliphatic hydrocarbon such as chloroform, dichlo-
`romethane, 1,1,1,2-tetrafluoroethane and 1,1,2-trichloroet-
`hene; edible fat and oil such as sesame oil, corn oil, olive oil
`and cotton seed oil; liquefied aliphatic hydrocarbon such as
`methane, ethane, propane, propylene, butane and butylene;
`and dimethyl sulfoxide.
`
`[0050] With regard to a sole solvent, aqueous medium,
`alcohol or aliphatic ketone is preferred. With regard to the
`alcohol, monohydric aliphatic alcohol is more preferred and
`ethanol is particularly preferred. With regard to an aliphatic
`ketone, acetone is preferred.
`
`[0051] With regard to a mixed solvent, for example, an
`aqueous alcohol is preferred. An aqueous monohydric ali-
`phatic alcohol is more preferred and an aqueous ethanol is
`particularly preferred. As to the water content, it is preferred
`to be not more than 70% (v/v) and, more preferably, not
`more than 40% (v/v).
`
`[0052] With regard to the solvent, liquefied carbon dioxide
`and supercritical fluid carbon dioxide may be used.
`
`In extracting with a solvent, apparatus which are
`[0053]
`commonly used for extraction with solvent such as stirrer,
`ultrasonic wave generator, reflux extractor, Soxhlet extrac-
`tor, homogenizer and shaker may be used.
`
`[0054] There is no particular limitation for the amount of
`the solvent used for the extraction with solvent and, for
`example, 0.1 to 10,000 part(s) by weight or, preferably, 1 to
`100 part(s) by weight of the solvent is used to 1 part by
`weight of the plant of the present invention. With regard to
`the extracting temperature, although there is no particular
`limitation provided that it is the temperature of not lower
`than melting point and not higher than boiling point of the
`solvent, it is preferably 0 to 100° C. and, more preferably, 20
`to 90° C. in the case of an aqueous medium while, in the case
`of organic solvent, it is preferably 0 to 1,000° C. and, more
`preferably, 20 to 90° C. Although there is no particular
`limitation for the extracting time, it is preferably 1 minute to
`1 week and, more preferably, 30 minutes to 1 day.
`
`[0055] After completion of the extraction with a solvent,
`solid-liquid separation methods such as sedimentation, cake
`filtration, clear filtration, centrifugal filtration, centrifugal
`sedimentation, compression separation and filter press or,
`preferably, filtration is conducted to prepare an extracted
`liquid and that may be used as an extract. A residue prepared
`by the above solid-liquid separation methods may be further
`extracted with an extracting solvent to use as an extract.
`
`[0056] When a supercritical fluid extraction (which may
`be merely called supercritical extraction) is conducted, an
`extracting fluid may be used solely, but it is also possible to
`use a mixture of an extracting fluid with an entrainer.
`
`[0057] With regard to the extracting fluid, any of super-
`critical fluids such as carbon dioxide, ammonia, methanol,
`ethanol, isopropyl alcohol, ethane, propane, butane, pentane,
`hexane, dimethylbutane, benzene, dichlorodifluoromethane,
`dichlorofluoromethane, trichlorofluoromethane, dichlorotet-
`rafluoromethane,
`chlorotrifluoromethane,
`diethyl
`ether,
`ethyl methyl ether, hexane and dinitrogen monoxide may be
`used and supercritical carbon dioxide is preferably used.
`
`Incidentally, in the present invention, supercritical
`[0058]
`fluid (which may also be called supercritical gas) means
`fluid which is in a state beyond critical temperature and
`critical pressure.
`
`[0059] With regard to an entrainer, any of monohydric
`aliphatic alcohols such as methanol and ethanol, water,
`aqueous monohydric aliphatic alcohol, acetone, hexane, and
`the like may be used and ethanol is preferably used. The
`amount of the entrainer to be added is preferably 0.1 to 50%
`(w/w) and, more preferably, 1 to 20% (w/w).
`
`[0060] Although there is no particular limitation for the
`amount of extracting fluid to be used for the supercritical
`fluid extraction, it is used, for example, 5 to 1,000 parts by
`weight or, preferably, 20 to 50 parts by weight of extracting
`fluid as an accumulated amount to 1 part by weight of the
`plant of the present invention. If necessary, the extracting
`fluid may be circulated.
`
`[0061] Although there is no particular limitation for the
`amount of the entrainer to be used for the supercritical fluid
`extraction, it is, for example, 0.001 to 100 part(s) by weight
`or, preferably, 1 to 20 part(s) by weight as an accumulated
`amount to 1 part by weight of the supercritical fluid.
`
`[0062] A supercritical fluid extracting apparatus is used for
`the supercritical fluid extraction.
`
`[0063] Temperature and pressure of the extracting tank
`used for the supercritical fluid extraction should be higher
`than the critical temperature and critical pressure, respec-
`tively, although there is no particular limitation for their
`upper limits.
`
`temperature and critical pressure vary
`[0064] Critical
`depending upon the type of the compound and, in the case
`of carbon dioxide,
`temperature of the extracting tank is
`preferably 31.06 to 1,000° C. and, more preferably, 31.1 to
`60° C. while pressure of the extracting tank is preferably
`72.9 to 5,000 atm and, more preferably, 75 to 1,000 atm.
`Although there is no particular limitation for the pressure of
`the separating tank, it is preferably 1 to 5,000 atm and, more
`preferably, 1 to 1,000 atm.
`
`[0065] Although there is no particular limitation for the
`temperature of the separating tank used for the supercritical
`fluid extraction, it is preferably —273.16 to 1,000° C. and,
`more preferably, —80 to 200° C. Although there is no
`particular limitation for the extracting time, it is preferably
`1 minute to 100 hours and, more preferably, 20 minutes to
`5 hours.
`
`[0066] After completion of the supercritical fluid extrac-
`tion, an extracted liquid may be prepared by changing
`temperature and pressure of the separating tank, fillers, and
`the like. Examples of the separating method for the extract
`are isothermal vacuum method, isothermal gas-liquid sepa-
`rating method,
`isobaric heating method,
`isobaric cooling
`method, adsorbing method, and the like. After completion of
`the separating operation, the extract may be obtained as a
`solid or a liquid in the separating tank or, when an entrainer
`is used, it may be obtained as an entrainer solution.
`
`[0067] The extract of plant of the present invention may
`also be such a thing that an extract obtained by an extracting
`method such as solvent extraction or supercritical fluid
`extraction from the plant is further concentrated or treated
`with a drying method, a purifying method, etc.
`
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`
`[0068] Examples of concentration or drying methods are
`heating concentration, freezing concentration, reverse osmo-
`sis concentration, vacuum concentration,
`freeze-drying,
`natural drying, hot-air drying, air-drying, air-blowing dry-
`ing, spray drying, reduced-pressure drying, sun drying,
`vacuum drying, spray drying, fluidized-bed drying, foamed-
`bed drying, film drying using a drum drier, ultrasonic wave
`drying, electromagnetic wave drying, and the like, and
`vacuum concentration, spray drying method and freeze-
`drying method are preferably used.
`
`In the preparation of the extract of the plant of the
`[0069]
`present invention, it may be possible to conduct a device for
`not to inactive the active ingredient such as addition of
`antioxidant, preservative and the like or adjustment of
`heating temperature.
`
`[0070] The extract of the plant of the present invention
`may be prepared in such a manner that an extract residue
`prepared by extraction with various solvents, supercritical
`fluid extraction, and the like under a condition where the
`active ingredient is not or is hardly extracted from the plant
`of the present invention is further extracted by extraction
`with various solvents, supercritical fluid extraction, and the
`like under a condition where the active ingredient is able to
`be extracted. It is preferred to use a method where the
`residue obtained after extraction of the plant of the present
`invention or, preferably, dried product with an aqueous
`medium is extracted with alcohol, aqueous alcohol or ali-
`phatic ketone.
`
`[0071] Examples of the amino sugar or a salt thereof
`according to the present invention are glucosamine, galac-
`tosamine, neuraminic acid, N—acetylglucosamine, N—acetyl-
`galactosamine, N—acetylneuraminic
`acid, N—glycolyl-
`neuraminic acid and a salt thereof in which glucosamine or
`a salt thereof is preferably used. Examples of the salt in a salt
`of the amino sugar are hydrochloride, sulfate and phosphate,
`etc.
`
`[0072] With regard to glucosamine, a product prepared in
`such a manner, for example, that chitin obtained by removal
`of protein and removal of ash of shell of crustacean is
`hydrolyzed with concentrated hydrochloric acid, deacety-
`lated, decolorized, filtered, concentrated, separated, washed
`and dried may be used or a commercially available one (such
`as Glucosamine KHF manufactured by Kyowa High-Foods)
`may be used.
`
`[0073] Examples of the salt in glucosamine salt are hydro-
`chloride, sulfate (such as glucosamine-6-sulfate), phosphate
`(such as glucosamine-6-phosphate), and the like.
`
`[0074] Examples of the glycosaminoglycan in the present
`invention are hyaluronic acid, chondroitin, chondroitin sul-
`fate, keratin sulfate, heparin, heparan sulfate, dermatan
`sulfate and a salt thereof in which chondroitin sulfate or a
`
`salt thereof is preferably used.
`
`[0075] Examples of the salt in glycosaminoglycan salt are
`sodium salt, potassium salt, calcium salt, and the like.
`
`[0076] Chondroitin sulfate is a kind of mucopolysaccha-
`ride generally distributed in connective tissues of an animal
`mainly in cartilage. In the tissues, it is bound to protein and
`is present as proteoglycan.
`
`[0077] With regard to the chondroitin sulfate, it may be
`used as a purified one or in a form of proteoglycan, cartilage
`extract or dried cartilage powder.
`
`In order to obtain chondroitin sulfate in a form of
`[0078]
`proteoglycan, cartilage of, for example, marine animals such
`as shark and whale, mammals such as cattle and pig, birds,
`or the like is used as a material, extraction is conducted
`according to a known method such as neutral salt method,
`alkali method, enzyme method or autoclave method (for
`example, a method mentioned in Japanese Published Unex-
`amined Patent Application No. 2001-247602), fat, solids,
`and the like are removed and then dried. After fat and solids
`
`are removed, it is further treated for removal of protein using
`proteinase and purified according to a known method by
`means of alcohol precipitation which is described in Japa-
`nese Published Unexamined Patent Application No. 2001-
`247602,
`to thereby obtain chondroitin sulfate or a salt
`thereof in a pure state. A commercially available chondroitin
`sulfate or a salt thereof (such as Sodium Chondroitin Sulfate
`manufacture by Maruha) may be used.
`
`[0079] Examples of a salt in chondroitin sulfate salt are
`sodium salt, potassium salt and calcium salt in which sodium
`salt is used preferably.
`
`[0080] There is no particular limitation as to the arthritis to
`which the present invention can be applied, and examples
`include chlamydial arthritis, chronic absorptive arthritis,
`enteropathic arthritis, gonococcal arthritis, gouty arthritis,
`Jaccoud’s arthritis, juvenile arthritis, Lyme arthritis, ochro-
`notic arthritis, suppurative arthritis, osteoarthritis, shoulder
`periarthritis, arthritis caused by hyperkinesis, rheumatoid
`arthritis, and the like. The present invention is particularly
`effective for rheumatoid arthritis.
`
`[0081] The preventing or treating agent of the present
`invention can be produced by any method which has been
`well known in the technical field of pharmaceutics in such
`a manner that a product prepared by the above-mentioned
`method comprising plant or an extract of the plant and amino
`sugar or a salt thereof and/or glycosaminoglycan or a salt
`thereof (hereinafter, referred to active ingredient of the
`present invention) is mixed, if necessary, with one or more
`pharrnaceutically acceptable carrier(s).
`
`[0082] With regard to the active ingredient of the present
`invention, any of a combination of plant of the present
`invention or an extract of the plant with amino sugar or a salt
`thereof, a combination of plant of the present invention or an
`extract of the plant with glycosaminoglycan or a salt thereof
`and a combination of plant of the present invention or an
`extract of the plant with amino sugar or a salt thereof and
`glycosaminoglycan or a salt thereof may be used and it is
`preferred to be a combination of plant of the present inven-
`tion or an extract of the plant with amino sugar or a salt
`thereof and glycosaminoglycan or a salt thereof.
`
`the preventing or treating agent of the
`[0083] Further,
`present invention may, if necessary, comprise ingredient for
`prevention or treatment of other diseases. Moreover, other
`ingredient effective for preventing or treating arthritis may
`be added thereto as well.
`
`[0084] Examples of other ingredients effective for pre-
`venting or treating arthritis include boron, calcium, chro-
`mium, copper, magnesium, manganese, selenium, silicon,
`zinc, S-adenosylmethionine, collagen, collagen hydrolyzate,
`gelatin, gelatin hydrolyzate, bromelain,
`trypsin, chymot-
`rypsin, papain, rutin, carotenoid,
`flavonoid, anti-oxidant
`vitamin, y-linolenic acid, eicosapentaenoic acid, Boswellia,
`
`AKER EXHIBIT 2018 Page 5
`
`AKER EXHIBIT 2018 Page 5
`
`

`

`US 2006/0193962 A1
`
`Aug. 31, 2006
`
`capsaicin, cat’s claw, devil’s claw, feverfew, ginger, nettles,
`niacinamide, turmeric, curcumin, and the like. Other ingre-
`dients effective for preventing or treating arthritis may be in
`a pure form or as a mixture containing them or as an extract.
`
`It is desirable to administer a preventing or treating
`[0085]
`agent of the present invention through an effective route for
`preventing or treating arthritis and examples thereof are by
`oral administration and parenteral administration such as
`intravenous administration.
`
`[0086] With regard to the dosage form, any of oral prepa-
`rations such as tablets, powders, granules, pills, capsules,
`suspensions, emulsions, elixirs, syrups, liquid preparations,
`infusions, decoctions, extracts, tinctures and fluid extracts
`and parenteral preparations such as injections, drippings,
`creams and suppositories may be used although oral prepa-
`rations are preferably used.
`
`In preparing the oral preparations, additives such as
`[0087]
`excipient, binder, disintegrating agent, lubricant, dispersing
`agent, suspending agent, emulsifier, diluting agent, buffer,
`antioxidant and bacteria suppressing agent may be used.
`
`[0088] When the dosage form of the oral preparation is
`tablets, powder, granules, and the like, the preparation may
`be prepared by addition of saccharides such as lactose,
`sugar, glucose, sucrose, mannitol and sorbitol; starch such as
`that of potato, wheat and corn; inorganic substances such as
`calcium carbonate, calcium sulfate, sodium hydrogen car-
`bonate and sodium chloride; excipients such as crystalline
`cellulose and plant powder (e.g., licorice root powder and
`gentian powder); disintegrating agents such as starch, agar,
`gelatin powder, crystalline cellulose, carmellose sodium,
`carmellose calcium, calcium carbonate, sodium hydrogen
`carbonate and sodium alginate; lubricants such as magne-
`sium stearate, talc, hydrogenated plant oil, Macrogol and
`silicone oil; binders such as polyvinyl alcohol, hydroxypro-
`pyl cellulose, methyl cellulose, ethyl cellulose, carmellose,
`gelatin and starch paste; surfactants such as fatty acid ester;
`plasticizers such as glycerol; and the like.
`
`[0089] When dosage form of the oral preparation is a
`liquid preparation such as syrup, the preparation may be
`prepared by addition of diluents such as water, saccharides
`(e.g., sucrose, sorbitol and fructose), glycols (e.g., polyeth-
`ylene glycol and propylene glycol) and oils (e. g., sesame oil,
`olive oil and soybean oil); antiseptics such as p-hydroxy-
`benzoate; preservatives such as p-oxybenzoate derivatives
`(e.g., methyl p-oxybenzoate) and sodium benzoate; flavor
`such as strawberry flavor and peppermint; and the like.
`
`[0090] The formulation suitable for oral administration,
`e.g., extracts, tinctures or fluid extracts, may be prepared by
`using the extract obtained by extracting the plant body of the
`present invention with, for example, water, ethanol or a
`mixture of water and ethanol as such, or by concentrating the
`obtained extract.
`
`[0091] The formulation suitable for parenteral administra-
`tion preferably comprises a sterilized aqueous preparation
`containing an active ingredient of the present
`invention
`which is isotonic to the recipient’s blood. For example, for
`injections, an injectable solution may be prepared using a
`carrier such as a salt solution, a glucose solution, or a
`mixture of a salt solution and a glucose solution.
`
`oral preparations mentioned above, selected from diluents,
`antiseptics, preservatives, flavors, excipients, disintegrators,
`lubricants, binders, surfactants, and plasticizers.
`
`[0093] The dose and frequency of the administration of the
`agent for preventing or treating arthritis of the present
`invention depend on the dosage form, age and body weight
`of the patient, and the symptom and degree of the disease to
`be treated, and the like. For example, in oral administration,
`it is administered preferably in an amount of 0.001 to 50 g
`and, more preferably, 0.005 to 10 g, once or several times a
`day for an adult as a dried amount, of the plant of the present
`invention or an extract of the plant and amino sugar or a salt
`thereof and/or glycosaminoglycan or a salt
`thereof.
`In
`parenteral administration such as intravenous administra-
`tion, it is administered preferably in an amount of 0.0005 to
`50 g and, more preferably, 0.002 to 10 g, once or several
`times a day for an adult as a dried amount of the plant of the
`present invention or an extract of the plant and amino sugar
`or a salt thereof and/or glycosaminoglycan or a salt thereof.
`Period for the administration is usually one week to ten year
`and, preferably, one year to five years.
`
`[0094] Meanwhile, the preventing or treating agent of the
`present invention may be used not only for humans but also
`for animals other than humans (hereinafter, may also be
`referred to as non-human animals). Dose and dosage fre-
`quency when used for non-human animals is preferably
`0.002 to 10 g and, more preferably, 0.01 to 2 g as dried
`amount of the plant of the present invention or an extract of
`the plant and amino sugar or a salt thereof and/or glycosami-
`noglycan or a salt thereof per kg of body weight of the
`non-human animal once or several times a day. Period for
`the administration is usually one week to five years and,
`preferably, two weeks to two years.
`
`[0095] Composition ratio by weight of the dried substance
`of the plant of the present invention or an extract of the plan