L/ll/Bé
`
`Xi?
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`4,569,837
`
`United States Patent [191
`Suzuki et al.
`
`[11] Patent Number:
`[45] Date of Patent:
`
`4,569,837
`Feb. 11, 1986
`
`[54] PHARMACEUTICAL PREPARATION FOR
`REMEDY OF PERIODONTAL DISEASE AND
`PROCESS FOR PRODUCTION THEREOF
`[75] Inventors: Yoshiki Suzuki; Hiroshi Ikura, both
`of Hino; Toshihide Noguchi, Tokyo;
`Katsunori Izumizawa, Yokohama;
`Shiro Kinoshita, deceased, late of
`Tokyo, all of Japan, by Kimiko
`Kinoshita, Atsuhiro Kinoshita, heirs
`[73] Assignee: Teijin Limited, Osaka, Japan
`[21] Appl. No.: 616,510
`[22] Filed:
`Jun. 1, 1984
`[30]
`Foreign Application Priority Data
`Jun. 1, 1983 [JP]
`Japan ................................ .. 58-95752
`
`[51] Int. Cl.‘ ..................... .. A61L 15/03; A61K 9/70;
`A61K 31; A6lK 74
`[52] U.S. Cl. ...................................... .. 424/28; 424/78;
`514/953; 514/900; 514/902; 514/784
`[58] Field of Search .................. .. 424/28, 78; 514/953,
`514/900, 902, 781
`
`[56]
`
`References Cited
`U.S. PATENT DOCUMENTS
`
`3,972,995 8/1976 Tsuk et al. .......................... .. 424/28
`4,292,299 9/ 1981 Suzuki et a1. ....................... .. 424/28
`
`FOREIGN PATENT DOCUMENTS
`
`822075 9/1969 Canada ................................ .. 424/28
`56-100714 8/1981 Japan ............ ..
`424/28
`WO80/009l6 5/1980 PCT Int’l Appl.
`424/21
`WO82/0ll29 4/1982 PCT Int’l Appl. ................. .. 424/28
`Primary Examiner-Shep K. Rose
`Attorney, Agent, or Firm—Sughrue, Mion, Zinn,
`Macpeak, and Seas
`ABSTRACT
`[57]
`A pharmaceutical preparation for remedy of periodon
`tal diseases, which is in the form of a film or sheet and
`is inserted in a periodontal pocket or gingiva, said phar
`maceutical preparation comprising a water-soluble pol
`ymeric substance having a Young’s modulus of 10 to
`250 Kg/rnrn2 as determined at a temperature of 25° C.
`and a relative humidity of 65%, and a viscosity of the
`2% aqueous solution of 5 to 30,000 CP as determined at
`20° C. and a medicinal agent for remedy of periodontal
`diseases. This pharmaceutical preparation can be pre
`pared by dissolving the above-mentioned water-soluble
`polymeric substance and medicinal agent in an organic
`solvent, casting the resultant solution, and removing the
`organic solvent by drying to obtain a pharmaceutical
`preparation in the form of a ?lm or sheet.
`
`9 Claims, No Drawings
`
`MYLAN - EXHIBIT 1011
`
`

`
`1
`1
`
`PHARMACEUTICAL PREPARATION FOR
`PHARMACEUTICAL PREPARATION FOR
`REMEDY OF PERIODONTAL DISEASE AND
`REMEDY OF PERIODONTAL DISEASE AND
`PROCESS FOR PRODUCTION THEREOF
`PROCESS FOR PRODUCTION THEREOF
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`ever, none of these methods have a decisive curative
`ever, none of these methods have a decisive curative
`effect.
`effect.
`There has recently been reported a method in which
`There has recently been reported a method in which
`an antibacterial agent is included in a strip composed of
`an antibacterial agent is included in a strip composed of
`a water-insoluble polymeric substance such as poly
`a water-insoluble polymeric substance such as poly-
`(ethyl methacrylate) and the strip is placed in a peri
`(ethyl methacrylate) and the strip is placed in a peri-
`odontal pocket to kill anaerobic bacteria in the peri
`odontal pocket to kill anaerobic bacteria in the peri-
`odontal pocket [M. Addy et al.; J. Periodontol, Novem-
`odontal pocket [M. Addy et al.; J. Periodontol, Novem
`ber, 693 (l982].
`ber, 693 (1982].
`However, according to this method, since a water-
`However, according to this method, since a water
`insoluble polymeric substance is used, if the strip is left
`insoluble polymeric substance is used, if the strip is left
`in the periodontal pocket, a pain or irritation is readily
`in the periodontal pocket, a pain or irritation is readily
`given to the affected part.
`given to the affected part.
`SUMMARY OF THE INVENTION
`SUMMARY OF THE INVENTION
`Accordingly, the object of the present invention is to
`Accordingly, the object of the present invention is to
`provide a pharmaceutical preparation for remedy of
`provide a pharmaceutical preparation for remedy of
`periodontal diseases, which comprises a medicinal agent
`periodontal diseases, which comprises a medicinal agent
`capable of killing bacteria and bacterial plexus in a peri
`capable of killing bacteria and bacterial plexus in a peri-
`odontal pocket, which are fundamental causes of peri
`odontal pocket, which are fundamental causes of peri-
`odontal diseases, and of moderating inflammation, and a
`odontal diseases, and of moderating in?ammation, and a
`polymeric substance which has a flexibility such that
`polymeric substance which has a ?exibility such that
`the pharmaceutical preparation can be easily carried to
`the pharmaceutical preparation can be easily carried to
`the bottom of the periodontal pocket or the bottom of
`the bottom of the periodontal pocket or the bottom of
`the gingival region as the boundary between the gingiva
`the gingival region as the boundary between the gingiva
`and teeth, such a water-solubility that, after the adminis-
`and teeth, such a water-solubility that, after the adminis
`tration, the pharmaceutical preparation does not give an
`tration, the pharmaceutical preparation does not give an
`alien solid feeling causing a pain or irritation in the
`alien solid feeling causing a pain or irritation in the
`affected part and such physical properties that the poly
`affected part and such physical properties that the poly-
`metic substance is dissolved in the body fluid or extrud-
`metic substance is dissolved in the body ?uid or extrud
`ate to form a viscous liquid which is present in the
`ate to form a viscous liquid which is present in the
`periodontal pocket or gingival region for a certain time
`periodontal pocket or gingival region for a certain time
`so that the medicinal agent is made resident in a part
`so that the medicinal agent is made resident in a part
`within the periodontal pocket or gingival region to
`within the periodontal pocket or gingival region to
`increase the curative effect.
`increase the curative effect.
`Another object of the present invention is to provide
`Another object of the present invention is to provide
`a process for the production of a pharmaceutical prepa-
`a process for the production of a pharmaceutical prepa
`ration for_ remedy of periodontal diseases.
`ration for_ remedy of periodontal diseases.
`Other objects and advantages of the present invention
`Other objects and advantages of the present invention
`will be apparent from the following description.
`will be apparent from the following description.
`In accordance with the present invention, there is
`In accordance with the present invention, there is
`“provided a pharmaceutical preparation for remedy of
`I provided a pharmaceutical preparation for remedy of
`periodontal diseases, which is in the form of a film or
`periodontal diseases, which is in the form of a ?lm or
`sheet and is inserted in a periodontal pocket or gingiva,
`sheet and is inserted in a periodontal pocket or gingiva,
`comprising a water-soluble polymeric substance having
`comprising a water-soluble polymeric substance having
`a Young’s modulus of 10 to 250 Kg/mm? as determined
`a Young’s modulus of 10 to 250 Kg/mm2 as determined
`at a temperature of 25° C. and a relative humidity of
`at a temperature of 25° C. and a relative humidity of
`65%, and a viscosity of the 2% aqueous solution of 5 to
`65%, and a viscosity of the 2% aqueous solution of 5 to
`30,000 CP as determined at 20° C. and a medicinal agent
`30,000 CP as determined at 20° C. and a medicinal agent
`for remedy of periodontal diseases.
`for remedy of periodontal diseases.
`In accordance with the present invention, there is
`In accordance with the present invention, there is
`also provided a process for the production the above-
`also provided a process for the production the above
`mentioned pharmaceutical preparation comprising the
`mentioned pharmaceutical preparation comprising the
`steps of dissolving a water-soluble polymeric substance
`steps of dissolving a water-soluble polymeric substance
`having a Young’s modulus of 10 to 250 Kg/mmz as
`having a Young’s modulus of 10 to 250 Kg/mm2 as
`determined at a temperature of 25° C. and a relative
`determined at a temperature of 25° C. and a relative
`humidity of 65%, and a viscosity of the 2% aqueous
`humidity of 65%, and a viscosity of the 2% aqueous
`solution of 5 to 30,000 CP as determined at 20° C. and a
`solution of 5 to 30,000 CP as determined at 20° C. and a
`medicinal agent for remedying periodontal diseases.
`medicinal agent for remedying periodontal diseases.
`DESCRIPTION OF THE PREFERRED
`DESCRIPTION OF THE PREFERRED
`EMBODIMENTS
`EMBODIMENTS
`Research was carried out with a view to developing
`Research was carried out with a view to developing
`a pharmaceutical preparation for remedy of periodontal
`a pharmaceutical preparation for remedy of periodontal
`diseases such as pyorrhea alveolaris, having a flexibility
`diseases such as pyorrhea alveolaris, having a ?exibility
`such as facilitating the arrival of the pharmaceutical
`such as facilitating the arrival of the pharmaceutical
`preparation at the bottom of a periodontal pocket or
`preparation at the bottom of a periodontal pocket or
`gingival region, being capable of retaining a medicinal
`gingival region, being capable of retaining a medicinal
`
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`50
`
`BACKGROUND OF THE INVENTION
`BACKGROUND OF THE INVENTION
`1. Field of the Invention
`1. Field of the Invention
`The present
`invention relates to a pharmaceutical
`The present invention relates to a pharmaceutical
`preparation for remedy of periodontal disease. More
`preparation for remedy of periodontal disease. More
`particularly, the present invention relates to a pharrna-
`particularly, the present invention relates to a pharma
`ceutical preparation for remedy of periodontal diseases,
`ceutical preparation for remedy of periodontal diseases,
`which is in the form of a film or sheet and is inserted in
`which is in the form of a ?lm or sheet and is inserted in
`a periodontal pocket or gingiva, comprising a medicinal
`a periodontal pocket or gingiva, comprising a medicinal
`agent for remedy of periodontal diseases, which has
`agent for remedy of periodontal diseases, which has
`medicinal actions such as a germicidal action, an anti-
`medicinal actions such as a germicidal action, an anti
`bacterial action, a plaque-dissolving action and an anti-
`bacterial action, a plaque-dissolving action and an anti
`in?ammatory action, and a water-soluble polymeric
`inflammatory action, and a water-soluble polymeric
`substance having a Young’s modulus of 10 to 250
`substance having a Young’s modulus of 10 to 250
`Kg/mmz as determined at a temperature of 25° C. and a
`Kg/mmZ as determined at a temperature of 25° C. and a
`relative humidity of 65%, and a viscosity of 5 to 30,000
`relative humidity of 65%, and a viscosity of 5 to 30,000
`CP as determined at 20° C. with respect to a 2% aque-
`CP as determined at 20° C. with respect to a 2% aque
`ous solution, and also relates to a process for the pro-
`ous solution, and also relates to a process for the pro
`duction of this pharmaceutical preparation for remedy
`duction of this pharmaceutical preparation for remedy
`of periodontal diseases.
`of periodontal diseases.
`2. Description of the Prior Art
`2. Description of the Prior Art
`By “periodontal diseases” are meant all diseases oc-
`By “periodontal diseases” are meant all diseases oc
`curring in the periodontal tissue. The main periodontal
`curring in the periodontal tissue. The main periodontal
`diseases are gingivitis and chronic parodontitis margina-
`diseases are gingivitis and chronic parodontitis margina
`lis. Chronic parodontitis marginalis is called “pyorrhea
`lis. Chronic parodontitis marginalis is called “pyorrhea
`alveolaris”, and 50 to 70% of adults of thirty years and
`alveolaris”, and 50 to 70% of adults of thirty years and
`over suffer from this diseases more or less. Pyorrhea
`over suffer from this diseases more or less. Pyorrhea
`alveolaris is a chronic disease of the periodontal tissue,
`alveolaris is a chronic disease of the periodontal tissue,
`the main complaints of which are the drainage of pus
`the main complaints of which are the drainage of pus
`from the gingiva, the absorption of an alveolar bone,
`from the gingiva, the absorption of an alveolar bone,
`and the relaxation and tottering of teeth. It was consid-
`and the relaxation and tottering of teeth. It was consid
`ered that the main causes of pyorrhea alveolaris are
`ered that the main causes of pyorrhea alveolaris are
`general disorders such as hormone imbalance, abnormal
`general disorders such as hormone imbalance, abnormal
`metabolism, and avitaminosis but it has recently been
`metabolism, and avitaminosis but it has recently been
`proved that the main cause of pyorrhea alveolaris is a
`proved that the main cause of pyorrhea alveolaris is a
`local in?ammatory factor in the periodontal portion,
`local inflammatory factor in the periodontal portion,
`which is due mainly to a plaque. The plaque is a bacte-
`which is due mainly to a plaque. The plaque is a bacte
`rial plexus of oral bacteria, which is deposited on a
`rial plexus of oral bacteria, which is deposited on a
`groove of the tooth surface, a boundary between teeth,
`groove of the tooth surface, a boundary between teeth,
`or a boundary between a tooth and gingiva. Inflamma-
`or a boundary between a tooth and gingiva. In?amma
`tion is caused by bacteria in the plaque or metabolites
`tion is caused by bacteria in the plaque or metabolites
`thereof, and this inflammation extends to the deep por-
`thereof, and this in?ammation extends to the deep por
`tion to form a gingival pocket (periodontal pocket).
`tion to form a gingival pocket (periodontal pocket).
`This state is called pyorrhea alveolaris.
`This state is called pyorrhea alveolaris.
`As the curative means, there are adopted an antiphlo-
`As the curative means, there are adopted an antiphlo
`gistic treatment, a load relieving method, and a home
`gistic treatment, a load relieving method, and a home
`curative treatment mainly for improving the affected
`curative treatment mainly for improving the affected
`gingival pocket and repairing the lesion of the periodon
`gingival pocket and repairing the lesion of the periodon-
`tal tissue. According to the antiphlogistic treatment, the
`tal tissue. According to the antiphlogistic treatment, the
`affected gingival pocket is improved by curettage of the
`affected gingival pocket is improved by curettage of the
`affected gingival pocket, removal of tartar or cutting or
`affected gingival pocket, removal of tartar or cutting or
`cauterization of the gingiva, and the affected part is
`cauterization of the gingiva, and the affected part is
`rendered antiphlogistic by washing and the injection of
`rendered antiphlogistic by washing and the injection of
`a medicine. According to the load relieving method,
`a medicine. According to the load relieving method,
`occlusion is adjusted, and according to the home cura-
`occlusion is adjusted, and according to the home cura
`tive treatment, teeth are cleaned and gingiva is mas-
`tive treatment, teeth are cleaned and gingiva is mas
`saged by the patient. Furthermore, there is adopted a
`saged by the patient. Furthermore, there is adopted a
`method in which a solution of an antibacterial agent is
`method in which a solution of an antibacterial agent is
`irrigated or injected into the periodontal region and the
`irrigated or injected into the periodontal region and the
`interior of the periodontal pocket (see, for example, J.
`interior of the periodontal pocket (see, for example, J.
`H. Hardy, H. N. Newman, J. D. Strahan; J. Clinical
`H. Hardy, H. N. Newman, I. D. Strahan; J. Clinical
`Periodontology, September 1982, pages 57-65). How-
`Periodontology, September 1982, pages 57-65). How
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`agent in the pocket for a long time, and giving no pain
`agent in the pocket for a long time, and giving no pain
`rpm and the liquid amount is 500 ml), more than 50% of
`rpm and the liquid amount is 500 ml), more than 50% of
`or irritation to the affected part. As the result, it was
`the polymeric substance is not dissolved out within 30
`or irritation to the affected part. As the result, it was
`the polymeric substance is not dissolved out within 30
`found that this object can be attained by the above-men-
`found that this object can be attained by the above-men
`minutes. When a water-soluble polymeric substance
`minutes. When a water-soluble polymeric substance
`tioned pharmaceutical preparation which is in the form
`tioned pharmaceutical preparation which is in the form
`having a water solubility included within the above-
`having a water solubility included within the above
`of a film or sheet and is inserted in a periodontal pocket
`of a film or sheet and is inserted in a periodontal pocket
`mentioned range, the residence property of the pharma
`mentioned range, the residence property of the pharma-
`or gingiva.
`or gingiva.
`ceutical preparation inserted in a gingival region or
`ceutical preparation inserted in a gingival region or
`According to the present invention, a water-soluble
`periodontal pocket is improved.
`According to the present invention, a water-soluble
`periodontal pocket is improved.
`polymertic substance having a Young’s modulus of 10
`polymertic substance having a Young’s modulus of 10
`As speci?c examples of the water-soluble polymeric
`As specific examples of the water-soluble polymeric
`to 250 Kg/mmz as determined at a temperature of 25° C.
`to 250 Kg/mm2 as determined at a temperature of 25° C.
`substance, there can be mentioned lower alkyl ethers of
`substance, there can be mentioned lower alkyl ethers of
`and a relative humidity of 65%, and a viscosity of the
`and a relative humidity of 65%, and a viscosity of the
`cellulose such as methyl cellulose, hydroxyethyl cellu-
`cellulose such as methyl cellulose, hydroxyethyl cellu
`2% aqueous solution of 5 to 30,000 CP as determined at
`2% aqueous solution of 5 to 30,000 CP as determined at
`lose, hydroxypropyl cellulose, hydroxypropylmethyl
`lose, hydroxypropyl cellulose, hydroxypropylmethyl
`20° C. is used as the base.
`20° C. is used as the base.
`cellulose and sodium carboxymethyl cellulose, water-
`cellulose and sodium carboxymethyl cellulose, water
`By the Young’s modulus referred to in the present
`By the Young’s modulus referred to in the present
`soluble vinyl polymers such as polyvinyl alcohol, poly
`soluble vinyl polymers such as polyvinyl alcohol, poly-
`invention is meant
`the
`initial Young’s modulus
`invention is meant the initial Young’s modulus
`vinyl pyrrolidone, polyacrylic acid, copolymers of
`vinyl pyrrolidone, polyacrylic acid, copolymers of
`(Kg/mmz) obtained when a sheet or film having a width
`(Kg/mmz) obtained when a sheet or ?lm having a width
`methacrylic acid, styrene or a vinyl type ether mono-
`methacrylic acid, styrene or a vinyl type ether mono
`of 1 cm and a thickness about 0.25 mm is pulled in a
`of 1 cm and a thickness about 0.25 mm is pulled in a
`mer with acrylic acid and salts thereof, and alginic acid
`mer with acrylic acid and salts thereof, and alginic acid
`tensile strength tester at a chuck distance of 2 cm. When
`tensile strength tester at a chuck distance of 2 cm. When
`and the salts thereof, gelatin, pullulan, starch deriva-
`and the salts thereof, gelatin, pullulan, starch deriva
`a water-soluble polymeric substance having such a flex-
`a water-soluble polymeric substance having such a ?ex
`tives, and polyoxyalkylenes such as high molecular
`tives, and polyoxyalkylenes such as high molecular
`ibility that the Young’s modulus is within the above
`ibility that the Young’s modulus is within the above-
`weight polyethylene glycol. Mixtures of two or more of
`weight polyethylene glycol. Mixtures of two or more of
`mentioned range is used, the obtained pharmaceutical
`mentioned range is used, the obtained pharmaceutical
`these water-soluble polymeric substances also can be
`these water-soluble polymeric substances also can be
`preparation has a characteristic wherein the pharma-
`preparation has a characteristic wherein the pharma
`used. Among these water-soluble polymeric substances,
`used. Among these water-soluble polymeric substances,
`ceutical preparation is administered,
`it can easily be
`ceutical preparation is administered, it can easily be
`lower alkyl ethers of cellulose, water-soluble vinyl pol
`lower alkyl ethers of cellulose, water-soluble vinyl pol-
`guided to the bottom of a periodontal pocket or gingival
`guided to the bottom of a periodontal pocket or gingival
`ymers and mixtures of two or more of them are pre-
`ymers and mixtures of two or more of them are pre
`region. By the term “periodontal pocket” used herein is
`region. By the term “periodontal pocket” used herein is
`ferred, and methyl cellulose, sodium carboxymethyl
`ferred, and methyl cellulose, sodium carboxymethyl
`meant a gingival pocket, that is, a groove or clearance
`meant a gingival pocket, that is, a groove or clearance
`cellulose, hydroxypropyl cellulose, hydroxypropyl
`cellulose, hydroxypropyl cellulose, hydroxypropyl-
`formed between the tooth and gingiva by perodontitis
`formed between the tooth and gingiva by perodontitis
`methyl cellulose, polyvinyl pyrrolidone, a mixture of
`methyl cellulose, polyvinyl pyrrolidone, a mixture of
`or the like. Furthermore, by the term “gingival region”
`or the like. Furthermore, by the term “gingival region”
`hydroxypropyl cellulose and polyacrylic acid or a salt
`hydroxypropyl cellulose and polyacrylic acid or a salt
`is meant a groove or clearance formed in the boundary
`is meant a groove or clearance formed in the boundary
`thereof, and a mixture of hydroxypropyl cellulose and
`thereof, and a mixture of hydroxypropyl cellulose and
`between the tooth and gingiva by artificial means or a
`between the tooth and gingiva by arti?cial means or a
`sodium carboxymethyl cellulose are especially pre
`sodium carboxymethyl cellulose are especially pre-
`gingival portion left after curettage of a periodontal
`gingival portion left after curettage of a periodontal
`ferred. Methyl cellulose, hydroxypropyl cellulose, and
`ferred. Methyl cellulose, hydroxypropyl cellulose, and
`pocket. It is preferred that the Young’s modulus of the
`pocket. It is preferred that the Young’s modulus of the
`a mixture of hydroxypropyl cellulose and polyacrylic
`a mixture of hydroxypropyl cellulose and polyacrylic
`polymeric substance be 15 to 200 Kg/mmz, especially
`polymeric substance be 15 to 200 Kg/mmz, especially
`acid or its salt are most preferred.
`acid or its salt are most preferred.
`20 to 180 Kg/mmz.
`20 to 180 Kg/mmz.
`Any of medicines effective for prevention and rem-
`Any of medicines effective for prevention and rem
`It is indispensable in the present invention that the
`It is indispensable in the present invention that the
`edy of periodontal diseases can be used as the medicinal
`edy of periodontal diseases can be used as the medicinal
`viscosity of a 2% aqueous solution of the water-soluble
`viscosity of a 2% aqueous solution of the water-soluble
`agent in the present invention. As the medicinal agent,
`agent in the present invention. As the medicinal agent,
`polymeric substance should be 5 to 30,000 CP as deter-
`polymeric substance should be 5 to 30,000 CP as deter
`there can be mentioned germicidal agents such as chlo-
`there can be mentioned germicidal agents such as chlo
`mined at 20° C. If a water-soluble polymeric substance
`mined at 20° C. If a water-soluble polymeric substance
`rohexidine, thimerosal, silver protein, chloramine,
`io-
`rohexidine, thimerosal, silver protein, chloramine, io
`having a viscosity included within the above-mentioned
`having a viscosity included within the above-mentioned
`dine glycerin, iogloform, boric acid, paraformaldehyde,
`dine glycerin, iogloform, boric acid, paraformaldehyde,
`range is used, when the pharmaceutical preparation is
`range is used, when the pharmaceutical preparation is
`phenol, hexylres'orcinol, benzalkonium chloride, benze
`phenol, hexylresorcinol, benzalkonium chloride, benze-
`inserted into a periodontal pocket or gingival region,
`inserted into a periodontal pocket or gingival region,
`thonium
`chloride,
`chlorhexidine
`gluconate,
`thonium
`chloride,
`chlorhexidine
`gluconate,
`the medicinal agent can be retained at an affected part
`the medicinal agent can be retained at an affected part
`phenododecium bromide, dequalinium chloride, cetyl
`phenododecium bromide, dequalinium chloride, cetyl-
`of the periodontal pocket or gingival region for a long
`of the periodontal pocket or gingival region for a long
`pyridinium chloride, and povidone iodine, antibacterial
`pyridinium chloride, and povidone iodine, antibacterial
`time without ?owing-out of the medicinal agent and the
`time without flowing-out of the medicinal agent and the
`agents such as tetracycline, tetracycline hydrochloride,
`agents such as tetracycline, tetracycline hydrochloride,
`curative effect of the medicinal agent can be exerted at
`curative effect of the medicinal agent can be exerted at
`benzylpenicillin, ampicillin, carbenicillin, acetylkitasa
`benzylpenicillin, ampicillin, carbenicillin, acetylkitasa-
`a high efficiency. It is preferred that the viscosity of the
`a high efficiency. It is preferred that the viscosity of the
`mycin, amoxyeillin, bacitracin, cephalotin sodium,
`mycin,
`amoxyeillin, bacitracin, cephalotin sodium,
`polymeric substance be 10 to 27,000 CP especially 20 to
`polymeric substance be 10 to 27,000 CP especially 20 to
`cephaloridine, cephalexin, erythromycin, chloramphen
`25,000 CP.
`cephaloridine, cephalexin, erythromycin, chloramphen-
`25,000 CP.
`icol, oxytetracycline hydrochloride, doxycycline hy
`icol, oxytetracycline hydrochloride, doxycycline hy-
`The base used in the present invention has the above-
`The base used in the present invention has the above
`drochloride, polymyxin B sulfate, fradiomycin sulfate,
`drochloride, polymyxin B sulfate, fradiomycin sulfate,
`mentioned Young’s modulus and viscosity and is a
`mentioned Young’s modulus and viscosity and is a
`and gentamicin sulfate, plaque-dissolving agents such as
`and gentamicin sulfate, plaque-dissolving agents such as
`water-soluble polymeric substance having such a water
`water-soluble polymeric substance having such a water
`lysozyme chloride, amylase, dextranase, and protease,
`lysozyme chloride, amylase, dextranase, and protease,
`solubility that is soluble in saliva or secreting fluid or
`solubility that is soluble in saliva or secreting ?uid or
`anti-in?ammatory agents such as sulpyrine, antipyrine,
`anti-inflammatory agents such as sulpyrine, antipyrine,
`exudate in the oral cavity. Since the pharmaceutical
`exudate in the oral cavity. Since the pharmaceutical
`aspirin, phenylbutazone, meprizole, oxyphenbutazone,
`aspirin, phenylbutazone, meprizole, oxyphenbutazone,
`preparation of the present invention comprises this
`preparation of the present
`invention comprises this
`fenbufen, mefenamic acid, flurbiprofen, diclofenac so-
`fenbufen, mefenamic acid, flurbiprofen, diclofenac so
`water-soluble polymeric substance, the surface portion
`water-soluble polymeric substance, the surface portion
`dium, ketoprofen, naproxen, tiaramid hydrochloride,
`dium, ketoprofen, naproxen,
`tiaramid hydrochloride,
`of the preparation is dissolved by saliva or the like to
`of the preparation is dissolved by saliva or the like to
`benzydamine hydrochloride, alclofenac, ibufenac, peri
`benzydamine hydrochloride, alclofenac, ibufenac, peri-
`some extent after administration into the periodontal
`some extent after administration into the periodontal
`soxalcitrate,
`ibuprofen,
`indomethacin,
`aluminum
`soxalcitrate,
`ibuprofen,
`indomethacin, aluminum
`pocket, and therefore, the preparation becomes adapted
`pocket, and therefore, the preparation becomes adapted
`flufenamate, thinoridine hydrochloride, clofezone, dex-
`?ufenamate, thinoridine hydrochloride, clofezone, dex
`to the periodontal pocket or gingival region and the
`to the periodontal pocket or gingival region and the
`amethasone, triamcinolone acetonide, and prostaglan-
`pain or irritation given to the affected part is moderated.
`amethasone, triamcinolone acetonide, and prostaglan
`pain or irritation given to the affected part is moderated.
`This is one of advantage attained by the pharmaceutical
`din, antihistaminic agents such as diphenhydramine
`This is one of advantage attained by the pharmaceutical
`din, antihistaminic agents such as diphenhydramine
`preparation of the present invention.
`«
`hydrochloride, chlorpheniramine maleate, and clemas
`hydrochloride, chlorpheniramine maleate, and clemas-
`preparation of the present invention.
`a
`It is preferred that the degree of the water solubilit
`tine, antibiotic agents such as sulfathiazole, sulfisomi-
`It is preferred that the degree of the water solubilit
`tine, antibiotic agents such as sulfathiazole, sul?somi
`be such that when the water-soluble polymeric sub-
`be such that when the water-soluble polymeric sub
`dine, and acetylfuratrizine, and local anesthetic agents
`dine, and acetylfuratrizine, and local anesthetic agents
`stance is compression-molded into a disc having a
`such as ethyl aminobenzoate and tetracaine hydrochlo-
`stance is compression-molded into a disc having a
`such as ethyl aminobenzoate and tetracaine hydrochlo
`weight of about 500 mg, a diameter of 13 mm and a
`ride. Mixtures of two or more of these medicinal agents
`weight of about 500 mg, a diameter of 13 mm and a
`ride. Mixtures of two or more of these medicinal agents
`thickness of about 3 to about 4 mm and the solubility is
`may be used. Among these medicinal agents, germicidal
`may be used. Among these medicinal agents, germicidal
`thickness of about 3 to about 4 mm and the solubility is
`tested in water according to the dissolution test method
`agents, antibacterial agents, plaque-dissolving agents,
`agents, antibacterial agents, plaque-dissolving agents,
`tested in water according to the dissolution test method
`of the Japanese Pharmacopoeia (the stirring speed is 200
`of the Japanese Pharmacopoeia (the stirring speed is 200
`and anti-inflammatory agents are preferred.
`and anti-inflammatory agents are preferred.
`
`45
`45
`
`35
`35
`
`4-0
`
`50
`
`55
`
`65
`65
`
`

`
`5
`5
`
`10
`
`15
`
`25
`25
`
`30
`30
`
`35
`
`EXAMPLES
`EXAMPLES
`The present invention will now be described in detail
`The present invention will now be described in detail
`with reference to, but is by no means limited to, the
`with reference to, but is by no means limited to, the
`following Examples.
`following Examples.
`
`4,569,837
`4,569,837
`5
`5
`6
`6
`the solution be allowed to stand still or be in vacuo for
`The amount used of the medicinal agent may be ap-
`The amount used of the medicinal agent may be ap
`the solution be allowed to stand still or be in vacuo for
`propriately determined according to the intensity of the
`propriately determined according to the intensity of the
`a while so that the solution is sufficiently deaerated. The
`a while so that the solution is suf?ciently deaerated. The
`pharmacological activity of the medicinal agent used
`pharmacological activity of the medicinal agent used
`solution is then cast. This casting is accomplished ac
`solution is then cast. This casting is accomplished ac-
`and the symptoms of the periodontal disease to be
`and the symptoms of the periodontal disease to be
`cording to a method in which the solution is uniformly
`cording to a method in which the solution is uniformly
`treated.
`treated.
`cast on a metal plate or glass plate, or by using a drum
`cast on a metal plate or glass plate, or by using a drum
`The pharmaceutical preparation of the invention of
`The pharmaceutical preparation of the invention of
`type ?lm preparing apparatus customarily adopted in a
`type film preparing apparatus customarily adopted in a
`this application is inserted into the periodontal pocket
`this application is inserted into the periodontal pocket
`solution casting method for production of films or an
`solution casting method for production of ?lms or an
`or gingival region, and it is administered in the form of
`or gingival region, and it is administered in the form of
`endless belt type ?lm preparing apparatus.
`endless belt type film preparing apparatus.
`a film or sheet. The size, shape, and thickness of the
`a ?lm or sheet. The size, shape, and thickness of the
`Then, the solvent is removed by drying. Drying is
`Then, the solvent is removed by drying. Drying is
`pharmaceutical preparation can be changed according
`pharmaceutical preparation can be changed according
`accomplished by air-drying, standing at room tempera
`accomplished by air-d