(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
`
`(19) World Intellectual Property Organization
`International Bureau
`
`26 April 2001 (26.04.2001) |||||||l||l||||l|||||||||||l||||ll||||||||llllllllll|||||l||ll||||||l||lllllllll
`
`(43) International Publication Date
`
`(10) International Publication Number
`WO 01/28563 A1
`
`
`(51) International Patent Classification7:
`9/51, 47/38
`
`A61K 31/58,
`
`ISHIDA, Takashi et al.; A. Aoki, Ishida &
`(74) Agents:
`Asscoiates, Toranomon 37 Mori Bldg., 5-1, Toranomon
`3-chome, Minato-ku, Tokyo 105-8423 (JP).
`
`(21) International Application Number:
`
`PCT/JP00/07351
`
`(22) International Filing Date: 20 October 2000 (20.10.2000)
`
`,
`,
`(25) “Mg Lang‘mge‘
`
`(26) Publication Language:
`
`.
`EnghSh
`
`English
`
`(81) Designated States (national): AE, AG, AL, AM, AT, AU,
`AZ: BA BB, BG, BR BY, th CA, CH CN, CR CU, CZ
`DE, DK, DM, DZ, EE, ES, FI, GB, GD, GE, GH, GM, HR,
`HU, ID, IL, IN, IS, JP, KE, KG, KR, KZ, LC, LK, LR, LS,
`LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NO,
`NZ, PL, PT, R0, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR,
`TT, TZ, UA, UG, US, UZ, VN, YU, ZA, ZW.
`
`(30) Priority Data:
`11/298186
`
`20 October 1999 (20.10.1999)
`
`JP
`
`(71) Applicant 0‘or all designated States except US): TEIJIN
`LIMITED [JP/JP]; 6-7, Minamihommachi 1-chome,
`Chuo-ku, Osaka—shi, Osaka 541—0054 (JP).
`
`(72) Inventors; and
`(75) Inventors/Applicants (for US only): NAGANO, At-
`suhiro [JP/JP]; Teijin Limited, Tokyo Research Center,
`3—2, Asahigaoka 4-chome, Hino-shi, Tokyo 191-0065 (JP).
`NISHIBE, Yoshihisa [JP/JP]; Teijin Limited,
`Iwakuni
`Research Center, 2-1, Hinode-cho,
`Iwakuni-shi, Yam-
`aguchi 740-0014 (JP). TAKANASHI, Kazuya [JP/JP];
`Teijin Limited, Tokyo Research Center, 3-2, Asahigaoka
`4—chome, Hino-shi, Tokyo 191—0065 (JP).
`
`(84) Designated States (regional): ARIPO patent (GH, GM,
`KE, LS, MW, MZ, SD, SL, sz, Tz, UG, ZW), Eurasian
`patent (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European
`Paltent (AT 313’ CH CY, DE» DK, ES» FL FR» GB GR, IE,
`FT, LU» MC, NL, PT, SE), OAPI patent (BF, BJ, CF, CG,
`CI, CM GA GN» GWr ML? MR, NE, SN TD TG)-
`
`Published:
`
`With international search report.
`Before the expiration of the time limit for amending the
`claims and to be republished in the event of receipt of
`amendments.
`
`For two-letter codes and other abbreviations, refer to the "Guid-
`ance Notes on Codes andAbbreviations ” appearing at the begin—
`ning ofeach regular issue ofthe PCT Gazette.
`
`
`
`(54) Title: CICLESONIDE-CONTAINJNG AQUEOUS PHARMACEUTICAL COMPOSITION
`
`||||||llllllllllllllll|||||||||Illlllllllllllllllllllllll|||||||||||l|||||||||||
`
`01/28563A1
`
`O (57) Abstract: The present invention provides an aqueous pharmaceutical composition contaimng ciclesonide and hydroxypropyl—
`methylcellulose, wherein the ciclesonide is dispersed in an aqueous medium in the form of solid particles. The composition is able to
`avoid variations in the concentrations of ciclesonide during production as well as avoid decreases in the recovery rate of ciclesonide.
`
`000001
`
`Exhibit 1 156
`
`Exhibit 1156
`IPR2017-00807
`ARGENTUM
`
`IPR2017-00807
`
`ARGENTUM
`
`000001
`
`

`

`WO 01/28563
`
`PCT/JP00/07351
`
`DESCRIPTION
`
`CICLESONIDE—CONTAINING AQUEOUS PHARMACEUTICAL COMPOSITION
`
`Field of Invention
`
`The present invention relates to a ciclesonide—
`
`containing aqueous pharmaceutical composition for use-in
`
`drug therapy that contains ciclesonide and
`hydroxypropylmethylcellulose, wherein said ciclesonide is
`
`dispersed in an aqueous medium in the form of solid
`
`10
`
`particles. More particularly,
`
`the present invention
`
`relates to a ciclesonide—containing aqueous
`
`15
`
`20
`
`pharmaceutical composition having excellent ciclesonide
`
`dispersivity during production as compared with
`
`conventional aqueous pharmaceutical compositions.
`
`Background Art
`
`ciclesonide aqueous pharmaceutical compositions
`
`containing ciclesonide dispersed in an aqueous medium in
`
`a form of solid particles are expected to represent a
`
`useful drug form for reasons that include 1) it is not
`
`necessary to completely dissolve ciclesonide, 2) it can
`be directly administered to an affected site by spraying
`
`and so forth for treatment of local diseases such as
`
`those of the nasal mucosa, eyes and epidermis, and 3)
`
`they are easier to swallow than tablets or granule and so
`
`25
`
`forth.
`
`When present in an aqueous medium, ciclesonide is
`
`resistant to wetting and easily aggregates.
`
`The addition
`
`of wetting agent such as Polysorbate 80 and powerful
`stirring and so forth during production have been used in
`
`30
`
`the prior art for the purpose of dispersing drug having
`
`such prOperties in an aqueous medium in a stable state.
`
`Improvement of drug dispersivity of aqueous
`
`pharmaceutical compositions containing a drug dispersed
`
`in an aqueous medium in form of solid particles by
`
`35
`
`addition of cellulose—based polymer is disclosed in
`
`Morishima et al. patent Specification of WO99-37286.
`
`However,
`
`this patent relates to the redispersion of a
`
`000002
`
`000002
`
`

`

`WO 01/28563
`
`PCT/JP00/07351
`
`drug that has settled during storage, and is
`
`fundamentally different from the present invention which
`
`relates to overcoming drawbacks of the migration of
`
`ciclesonide towards bubbles formed by powerful stirring
`
`during the production, and the adsorption of ciclesonide
`
`to the walls of the production apparatus. Moreover,
`
`the
`
`concentration of the cellulose—based polymer in the
`
`patent specification of Morishima et al.
`
`is 0.0001 to
`
`0.003%, and methylcellulose can be used in place of
`
`10
`
`hydroxypropylmethylcellulose for the cellulose—based
`
`polymer, while the addition of a nonionic surfactant is
`
`also required.
`
`It is not easy to deduce the present
`
`invention from this patent in which the optimum value of
`
`the hydroxypropylmethylcellulose concentration is from
`
`15
`
`0.01% w/w to 0.5% w/w, and does not require a surfactant.
`
`Disclosure of the Invention
`
`During the course of production of ciclesonide
`
`aqueous pharmaceutical compositions, high shearing force
`
`is required to disperse ciclesonide and it is necessary
`
`20
`
`to powerfully stir ciclesonide—containing aqueous
`
`pharmaceutical composition.
`
`ciclesonide migrates to the
`
`bubbles formed at this time.
`
`Since this results in an
`
`increased concentration of ciclesonide in the upper
`
`portion of the ciclesonide aqueous pharmaceutical
`
`25
`
`composition being higher than that in the lower portion,
`
`variation occurs in the ciclesonide concentration of
`
`ciclesonide aqueous pharmaceutical compositions produced.
`
`Moreover,
`
`the recovery rate decreases due to adsorption
`
`of ciclesonide to the walls and so forth of the
`
`30
`
`production apparatus.
`
`These variations in ciclesonide concentration and
`
`adsorption of ciclesonide to the production apparatus
`
`were hardly improved at all by the addition of wetting
`
`agents such as Polysorbate 80 that have been used in the
`
`35
`
`prior art. Conversely,
`
`the amount of formed bubbles
`
`increases resulting in promotion of further variation in
`
`ciclesonide concentration.
`
`000003
`
`000003
`
`

`

`WO 01/28563
`
`PCT/JPOO/07351
`
`Therefore,
`
`there is a considerable need for the
`
`development of a ciclesonide aqueous pharmaceutical
`
`composition that is able to avoid variations in
`
`ciclesonide concentrations during production as well as
`
`the decrease in ciclesonide recovery rate.
`
`Namely,
`
`the object of the present invention is to
`
`provide a ciclesonide aqueous pharmaceutical composition
`
`that avoids variations in ciclesonide concentration
`
`during production as well as decreases in the ciclesonide
`
`10
`
`recovery rate.
`
`As a result of earnest studies to solve the above
`
`problems,
`
`the inventors of the present invention found
`
`that a ciclesonide aqueous pharmaceutical composition can
`
`be provided that avoids variations in ciclesonide
`
`15
`
`concentrations during production as well as decreases in
`
`20
`
`25
`
`the ciclesonide recovery rate, by using a ciclesonide
`
`aqueous pharmaceutical composition containing ciclesonide
`
`and hydroxypropylmethylcellulose,
`
`thereby leading to
`
`completion of the present invention.
`
`Namely,
`
`the present invention relates to an aqueous
`
`pharmaceutical composition containing ciclesonide and
`
`hydroxypropylmethylcellulose, wherein said ciclesonide is
`
`dispersed in an aqueous medium in form of solid
`
`particles.
`
`Embodiment for Carrying Out the Invention
`
`It is essential that composition of the present
`
`invention contain ciclesonide, while water—soluble,
`
`water—low soluble or water—insoluble drugs other than
`
`ciclesonide can be added. Specific examples of these
`
`30
`
`include vasoconstrictors, bronchodilators, anti—allergic
`
`agents and expectorants.
`
`Although the ciclesonide particles that can be used
`
`in the present invention may be of any size,
`
`they are
`
`preferably within the range of 10 nm to 100 um, and
`
`35
`
`particularly preferably within the range of 10 nm to 10
`
`um.
`
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`
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`
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`

`WO 01/28563
`
`PCT/JP00/07351
`
`Although any substances may be used for the water—
`
`insoluble or water—low soluble substance that can be used
`
`in the present invention, a preferable example is a
`
`cellulose, and a particularly preferable example is
`
`crystalline cellulose.
`
`In the present invention,
`
`the concentration of
`
`water—insoluble substance and/or water—low soluble
`
`substance present in form of solid particles in an
`
`aqueous medium is preferably 0.3% w/w and above, and
`
`particularly preferably 1% w/w to 10% w/w, relative to
`
`the total amount of the composition.
`
`In addition, an aqueous polymer substance can also
`
`be added in the present pharmaceutical composition.
`
`Specific examples of such include propylene glycol
`
`alginate, pectin,
`
`low methoxyl pectin, gua gum, gum
`
`arabic, carrageenan, methylcellulose,
`
`carboxymethylcellulose sodium, xanthan gum and
`
`hydroxypropylcellulose, while particularly preferable
`
`examples include carboxymethylcellulose sodium,
`
`polyethylene glycol and hydroxypropylcellulose.
`
`In
`
`addition, crystalline cellulose carmellose sodium,
`
`is an
`
`example of a combination of these water—soluble
`
`substances and water—insoluble substances that can be
`
`10
`
`15
`
`20
`
`used in the present invention, and it consists of a
`
`25
`
`mixture of carboxymethylcellulose sodium and crystalline
`
`cellulose.
`
`Furthermore,
`
`in the case of adding these
`
`water—soluble polymer substances,
`
`the concentration of
`
`said substance is preferably 1% w/w to 30% w/w relative
`
`to the water—insoluble substance and/or water-low soluble
`
`3O
`
`substance.
`
`The ciclesonide—containing aqueous pharmaceutical
`
`composition of the present invention is also required to
`
`contain hydroxypropylmethylcellulose. Although this may
`
`be of any grade, a specific example is
`
`35
`
`hydroxypropylmethylcellulose 2910.
`
`Although said hydroxypropylmethylcellulose may be
`
`present at any concentration, its concentration is
`
`000005
`
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`
`

`

`WO 01/28563
`
`PCT/JP00/07351
`
`preferably from 0.01% w/w to 30% w/w, particularly
`
`preferably from 0.01% w/w to 5% w/w, more particularly
`
`preferably from 0.01% w/w to 1% w/w, and most preferably
`
`from 0.01% w/w to 0.5% w/w, relative to the total amount
`
`of composition.
`
`A wetting agent, although not essential in the
`
`present invention, can be added, specific examples of
`
`which include Polysorbate 80, glycerin monostearate,
`
`polyoxyl stearate,
`
`lauromacrogol, sorbitan oleate and
`
`10
`
`sucrose fatty acid esters.
`
`In the present invention, a substance for
`
`controlling osmotic pressure (osmotic pressure—
`
`controlling agent) can be added to control osmotic
`
`pressure, specific examples of which include salts such
`
`15
`
`as sodium chloride and water—soluble sugars such as
`
`glucose, with glucose being a particularly preferable
`
`example.
`
`An effective amount of ciclesonide used in the
`
`present invention can be determined according to the type
`
`20
`
`and degree of the respective disease, as well as the age
`
`and body weight of the patient, and so forth.
`
`The concentration of ciclesonide of the present
`
`invention is preferably from 0.01% w/w to 1% w/w, and
`
`particularly preferably from 0.05% w/w to 0.5% w/w,
`
`25
`
`relative to the total amount of the composition.
`
`Any method for dispersing a water—insoluble
`
`substance and/or water—low soluble substance in an
`
`aqueous medium may be used for the production of the
`
`ciclesonide—containing aqueous pharmaceutical composition
`
`3O
`
`in the present invention, a specific example of which is
`
`a method that uses a homomixer.
`
`Known antiseptics, pH controlling agents,
`
`preservatives, buffers, colorants, smell corrigents and
`
`so forth may be added as necessary to the composition of
`
`35
`
`the present invention to improve its physical properties,
`
`appearance or odor and so forth of the formulation.
`
`Examples of antiseptics include benzalkonium chloride,
`
`000006
`
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`

`WO 01/28563
`
`PCT/JP00/07351
`
`examples of pH controlling agents include hydrochloric
`
`acid and sodium hydroxide, examples of preservatives
`
`include ascorbic acid, examples of buffers include
`
`phosphoric acid and its salt, examples of colorants
`
`include red dye no. 2, and examples of smell corrigents
`
`include menthol.
`
`According to the present invention as described
`
`above, a ciclesonide aqueous pharmaceutical composition
`
`is provided that avoids variations in ciclesonide
`
`concentration during production as well as decreases in
`
`the recovery rate of ciclesonide more effectively than
`
`aqueous pharmaceutical compositions of the prior art.
`
`These effects also lead to improved quality as well as
`
`decreased production cost due to the higher recovery
`rate.
`
`Thus,
`
`the present invention has extremely high
`
`significance in terms of both quality and economy for the
`
`production of ciclesonide aqueous pharmaceutical
`
`compositions.
`
`Examples
`
`The following provides an explanation of the present
`
`invention through its Examples.
`
`ciclesonide used in the present invention was
`
`manufactured by Byk Gulden Co.,
`
`the crystalline cellulose
`
`carmellose sodium by Asahi Chemical Industry Co., Ltd.
`
`(AvicelTM RC—A591NF), hydroxypropylmethylcellulose 2910
`
`by Shin—Etsu Chemical Co., Ltd.
`
`(TC—5RWTM or Metrose
`
`6OSH—4000”), Polysorbate 80 by Nippon Surfactant Co.,
`
`Ltd., and the sorbitan trioleate by Nikko Chemical Co.,
`
`Ltd.
`
`ROBOMICSm manufactured by Tokushu Kika Kogyo Co.,
`
`Ltd. was used for the homomixer.
`
`Example 1
`
`ciclesonide aqueous pharmaceutical compositions
`
`containing the components indicated below were prepared
`
`on a 300 ml scale by processing with a homomixer.
`
`Homomixer processing was performed at 6000 rpm for 30
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`000007
`
`000007
`
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`

`WO 01/28563
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`PCT/JP00/07351
`
`minutes.
`
`Composition (1)
`
`Ciclesonide: 0.1% w/w
`
`Crystalline cellulose carmellose sodium: 1.7% w/w
`
`Hydroxypropylmethylcellulose 2910 (TC-SRWW):
`
`0.01% w/w
`
`Composition (2)
`
`Ciclesonide: 0.1% w/w
`
`Crystalline cellulose carmellose sodium: 1.7% w/w
`
`Hydroxypropylmethylcellulose 2910 (TC-5RW”):
`
`0.1% w/w
`
`Composition (3)
`
`Ciclesonide: 0.1% w/w
`
`Crystalline cellulose carmellose sodium: 1.7% w/w
`
`Hydroxypropylmethylcellulose 2910 (TC—SRWW):
`
`1% w/w
`
`Composition (4)
`
`Ciclesonide: 0.1% w/w
`
`Crystalline cellulose carmellose sodium: 1.7% w/w
`
`Hydroxypropylmethylcellulose 2910 (Metrose 6OSH-
`
`4000”): 0.01% w/w
`
`Composition (5)
`
`Ciclesonide: 0.1% w/w
`
`Crystalline cellulose carmellose sodium: 1.7% w/w
`
`Hydroxypropylmethylcellulose 2910 (Metrose GOSH-
`
`4000“): 0.1% w/w
`
`Immediately after processing compositions 1 to 5
`
`with the homomixer,
`
`the ciclesonide aqueous
`
`pharmaceutical compositions were collected from the upper
`
`followed
`and lower portions of the emulsification tank,
`by quantification of the ciclesonide concentrations by
`
`HPLC.
`
`The value for the upper portion of the
`
`emulsification tank was calculated by taking the
`
`ciclesonide concentration in the lower portion of the
`
`emulsification tank to be 100%.
`
`Subsequently,
`
`the ciclesonide concentrations of the
`
`10
`
`15
`
`20
`
`25
`
`3O
`
`35
`
`000008
`
`000008
`
`

`

`WO 01/28563
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`
`ciclesonide aqueous pharmaceutical compositions recovered
`
`from the emulsification tank were quantified by HPLC, and
`
`the ciclesonide recovery rates were determined based on
`
`the theoretical value of the ciclesonide concentration as
`
`5
`
`calculated from the charged amount.
`
`Those values are shown in Table 1.
`
`Comparative Example 1
`
`Ciclesonide aqueous pharmaceutical compositions
`
`containing the components indicated below were prepared
`
`10
`
`on a 300 ml scale by processing with a homomixer.
`
`Homomixer processing was performed at 6000 rpm for 30
`
`minutes.
`
`Composition (6)
`
`Ciclesonide: 0.1% w/w
`
`15
`
`Crystalline cellulose carmellose sodium: 1.7% w/w
`
`Polysorbate 80: 0.1% w/w
`
`Composition (7)
`
`Ciclesonide: 0.1% w/w
`
`Crystalline cellulose carmellose sodium: 1.7% w/w
`
`20
`
`Sorbitan trioleate: 0.1% w/w
`
`Immediately after processing compositions 6 and 7
`
`with the homomixer,
`
`the ciclesonide aqueous
`
`pharmaceutical compositions were collected from the upper
`
`and lower portions of the emulsification tank,
`
`followed
`
`25
`
`by quantification of the ciclesonide concentrations by
`
`HPLC.
`
`The value for the upper portion of the
`
`emulsification tank was calculated by taking the
`
`ciclesonide concentration in the lower portion of the
`
`emulsification tank to be 100%.
`
`30
`
`Subsequently,
`
`the ciclesonide concentrations of the
`
`ciclesonide aqueous pharmaceutical compositions recovered
`
`from the emulsification tank were quantified by HPLC, and
`
`the ciclesonide recovery rates were determined based on
`
`the theoretical value of the ciclesonide concentration as
`
`35
`
`calculated from the charged amount.
`
`Those values are shown in Table 1.
`
`000009
`
`000009
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`

`

`WO 01/28563
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`
`ciclesonide concentration
`
`
`
`Preparation
`Recovery
`rate (%)
`immediately after processing
`
`
`
`
`(%)
`
`
`Upper portion Lower portion
`
`
`
`of emulsi-
`of emulsi—
`
`
`fication tank fication tank
`
`
`
`
`
`
`
`Embodiment 1 Composition 1
`
`
`
`Composition 2
`———m
`
`
`
`
`
`
`
`
`
`
`Comparative
`
`Example 1
`
`
`100.4
`
`100 0
`
`100.8
`
`
`
`
`
`
`In the case of compositions 2,
`
`3 and 5, which
`
`contained 0.1 to 1% w/w of hydroxypropylmethylcellulose
`
`2910,
`
`the ciclesonide concentrations in the
`
`emulsification tank immediately after homomixer
`
`processing were uniform, and the recovery rates were
`
`almost 100%.
`
`In addition,
`
`in the case of compositions 1
`
`and 4, which contained 0.01% w/w of
`
`10
`
`hydroxypropylmethylcellulose 2910, although the
`
`ciclesonide concentrations in the emulsification tank
`
`immediately after homomixer processing were somewhat non—
`
`uniform,
`
`the recovery rates were almost 100%.
`
`In
`
`contrast,
`
`in the case of composition 6, which contained
`
`15
`
`0.1% w/w of Polysorbate 80,
`
`the ciclesonide concentration
`
`in the upper portion of the emulsification tank
`
`immediately after homomixer processing was more than 30%
`
`higher than in the lower portion.
`
`In addition,
`
`the
`
`recovery rate decreased by about 20%.
`
`In the case of
`
`20
`
`composition 7, which contained 0.1% w/w of sorbitan
`
`trioleate,
`
`the ciclesonide concentration in the upper
`
`portion of the emulsification tank immediately after
`
`homomixer processing was more than 40% higher than in the
`
`lower portion, and the recovery rate decreased by more
`
`25
`
`than half.
`
`000010
`
`000010
`
`

`

`WO 01/28563
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`
`_ 10 _
`
`Based on these results, it was determined that the
`
`use of a composition containing
`
`hydroxypropylmethylcellulose made it possible to avoid
`
`variation in the concentration of ciclesonide during
`
`production as well as avoid a decrease in the recovery
`
`rate of ciclesonide.
`
`00001 1
`
`000011
`
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`
`- 11 _
`
`CLAIMS
`
`1.
`
`An aqueous pharmaceutical composition
`
`containing ciclesonide and hydroxypropylmethylcellulose,
`
`wherein said ciclesonide is dispersed in an aqueous
`
`5
`
`medium in form of solid particles.
`
`2.
`
`An aqueous pharmaceutical composition according
`
`to claim 1 wherein said hydroxypropylmethylcellulose
`
`concentration is from 0.01% w/w to 30% w/w, relative to
`
`the total amount of the composition.
`
`10
`
`3.
`
`An aqueous pharmaceutical composition according
`
`to claim 1 wherein said hydroxypropylmethylcellulose
`
`concentration is from 0.01% w/w to 5% w/w, relative to
`
`the total amount of the composition.
`
`4.
`
`An aqueous pharmaceutical composition according
`
`15
`
`to claim 1 wherein said hydroxypropylmethylcellulose
`
`concentration is from 0.01% w/w to 1% w/w, relative to
`
`the total amount of the composition.
`
`5.
`
`An aqueous pharmaceutical composition according
`
`to claim 1 wherein said hydroxypropylmethylcellulose
`
`20
`
`concentration is from 0.01% w/w to 0.5% w/w, relative to
`
`the total amount of the composition.
`
`6.
`
`An aqueous pharmaceutical composition according
`
`to any of claims 1
`
`through 5 additionally containing one
`
`or more types of a water-insoluble substance and/or
`
`25
`
`water—low soluble substance.
`
`7.
`
`An aqueous pharmaceutical composition according
`
`to claim 6 wherein said water—insoluble substance and/or
`
`water—low soluble substance is a cellulose.
`
`8.
`
`An aqueous pharmaceutical composition according
`
`30
`
`to claim 7 wherein said cellulose is crystalline
`
`cellulose.
`
`9.
`
`An aqueous pharmaceutical composition according
`
`to any of claims 1
`
`through 8 additionally containing
`
`water—soluble polymer substance.
`
`35
`
`10.
`
`An aqueous pharmaceutical composition according
`
`to claim 9 wherein said water—soluble polymer substance
`
`is one or more types selected from the group consisting
`
`000012
`
`000012
`
`

`

`WO 01/28563
`
`PCT/JPOO/07351
`
`_ 12 _
`
`of polyethylene glycol, propylene glycol alginate,
`
`pectin,
`
`low methoxyl pectin, gua gum, gum arabic,
`
`carrageenan, methylcellulose, carboxymethylcellulose
`
`sodium, xanthan gum and hydroxypropylcellulose.
`
`11.
`
`An aqueous pharmaceutical composition according
`
`to claim 9 wherein said water—soluble polymer substance
`
`is carboxymethylcellulose sodium.
`
`12.
`
`An aqueous pharmaceutical composition according
`
`to claim 9 wherein said water—soluble polymer substance
`
`10
`
`is polyethylene glycol.
`
`13.
`
`An aqueous pharmaceutical composition according
`
`to claim 9 wherein said water-soluble polymer substance
`
`is hydroxypropylcellulose.
`
`14.
`
`An aqueous pharmaceutical composition according
`
`15
`
`to any of claims 1 through 13 wherein the combination of
`
`said water—insoluble substance and said water-soluble
`
`polymer substance is crystalline cellulose carmellose
`
`sodium.
`
`000013
`
`000013
`
`

`

`INTERNATIONAL SEARCH REPORT
`
`Internatii
`
`Application No
`
`PCT/JP 00/07351
`
`CLASSIFICATION OF S BJECT MATTER
`IPC 7
`A61K31 58
`A61K9/51
`
`A61K47/38
`
`According to International Patent Classification (lPC) orto both national classification and lPC
`B. FIELDS SEARCHED
`
`Minimum documentation searched (classification system followed by classification symbols)
`IPC 7
`A61K
`
`Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched
`
`Electronic data base consulted during the international search (name of data base and. where practical, search terms used)
`
`NPI Data, PAJ, CHEM ABS Data
`
`
`
`C. DOCUMENTS CONSIDERED TO BE RELEVANT
`
`Category °
`
`Citation of document, with indication, where appropriate, of the relevant passages
`
`Ftelevant to claim No
`
`NO 99 25359 A (ASTRA)
`27 May 1999 (1999—05—27)
`page 4,
`line 21
`claims 1,3,7,9—12,28-31
`page 8,
`line 4 — line 28
`page 9,
`line 19 —page 10,
`examples 4,5
`
`line 3
`
`ND 99 47144 A (PHARMALINK)
`23 September 1999 (1999—09—23)
`claims 1,2,6,14,16,18,22,23,25,28
`page 5,
`line 12 —page 6,
`line 7
`
`NO 98 52542 A (MINNESOTA MINING AND
`MANUFACTURING COMPANY)
`26 November 1998 (1998—11—26)
`claims
`
`examples
`
`A
`
`A
`
`1-14
`
`1—14
`
`1—14
`
`Further documents are listed in the continuation of box C.
`
`Patent family members are listed in annex.
`
`° Special categories of cited documents :
`
`'A' document defining the general state of the art which is not
`considered to be of particular relevance
`'E' earlier document but published on or afterthe international
`filing date
`'L' document which may throw doubts on priority claim(s) or
`which is cited to establish the publication date of another
`citation or other special reason (as specified)
`'0' document referring to an oral disclosure, use, exhibition or
`other means
`'P' document published prior to the international filing date but
`later than the priority date claimed
`
`'T'
`
`_
`_
`_
`.
`,
`later document published after the International filing date
`or piicrity date and not in conflict with the application but
`cited to understand the principle or theory underlying the
`invention
`'X' document of panicular relevance' the claimed invention
`cannot be considered novel or cannot be considered to
`involve an inventive step when the document is taken alone
`'Y' document of particular relevance" the claimed invention
`cannot be considered to involve an inventive step when the
`document is combined with one or more other such docu—
`ments. such combination being obvious to a person skilled
`I" the art.
`'8' document member of the same patent family
`
`Date of the actual completion of the international search
`
`Date of mailing of the international search report
`
`13 March 2001
`
`Name and mailing address of the ISA
`European Patent Office, PB. 5813 Patentlaan 2
`NL — 2280 HV Rijswijk
`Tel. (+31—70) 340—2040, Tx. 31 651 epo nl,
`Fax: (+3l—70) 340—3016
`Form PCT/lSA/210 (second sheet) (July 1992)
`
`23/03/2001
`
`Authorized officer
`
`.
`Scarponi , U
`
`omm14
`
`page 1 of“2
`
`000014
`
`

`

`INTERNATIONAL SEARCH REPORT
`
`
`
`Internati‘
`Application No
`
`
`PCT/JP 00/07351
`
`
`
`C.(Continuation) DOCUMENTS CONSIDERED TO BE RELEVANT
`
`Category °
`
`Citation of document. with indication,where appropriate, of the relevam passages
`
`Relevant to claim No.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`DATABASE WPI
`Section Ch, Week 199938
`Derwent Pub11cations Ltd., London, GB;
`C1ass A11, AN 1999-458604
`XP002162689
`& NO 99 37286 A (SANTEN PHARM CO LTD),
`29 Ju1y 1999 (1999-07-29)
`cited in the app11cation
`abstract
`
`
`
`
`Form PCT/ISN210 (continuation oi second sheet) (July 1992)
`
`omm15
`
`page~2 of 2’“
`
`
`
`000015
`
`

`

`INTERNATIONAL SEARCH REPORT
`Information on patent family members
`
`
`
`Patent document
`cited in search report
`
`Publication
`date
`
`
`Patent family
`member(s)
`
`
`Internatix
`Application No
`
`PCT/JP 00/07351
`Pu blication
`date
`
`
`
`
`
`
`27-05—1999
`
`NO 9925359
`
`A
`
`
`07—06-1999
`AU
`1266699 A
`03—10-2000
`BR
`9814118 A
`28-02-2001
`CN
`1285750 T
`06-09-2000
`EP
`1032396 A
`05-07-2000
`N0
`20002470 A
`
`ZA
`9810217 A
`14-05-1999
`
`
` 514128 08-01-2001
`AU
`2968699
`11-10-1999
`BR
`9908838
`12—12-2000
`EP
`1056461
`06—12-2000
`9800905 18—09*1999
`
`
`26-11-1998
`
`NO 9852542
`
`A
`
`AU
`726835 B
`23-11-2000
`AU
`7496298 A
`11-12—1998
`BG
`103902 A
`31-05-2000
`BR
`9809448 A
`20—06-2000
`CN
`1257421 T
`21—06-2000
`EP
`0983058 A
`08-03-2000
`NO
`995667 A
`18-11-1999
`PL
`336885 A
`17-07—2000
`SK
`157699 A
`16-05-2000
`
`19-09—2000 6120752 A
`
`NO 9937286
`
`A
`
`EP
`08-11-2000
`1050299 A
`JP
`12-10-1999
`11279052 A
`
`
`05-09-2000 20003650 A
`
`29-07-1999
`
`
`
`Form PCT/ISN210 (patent family annex) (July 1992)
`
`000016
`
`000016
`
`