JP6826695B2 - Pharmaceutical composition - Google Patents
Pharmaceutical composition Download PDFInfo
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- JP6826695B2 JP6826695B2 JP2020515986A JP2020515986A JP6826695B2 JP 6826695 B2 JP6826695 B2 JP 6826695B2 JP 2020515986 A JP2020515986 A JP 2020515986A JP 2020515986 A JP2020515986 A JP 2020515986A JP 6826695 B2 JP6826695 B2 JP 6826695B2
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- Prior art keywords
- pharmaceutical composition
- salt
- composition according
- sulfate
- taumatin
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 84
- 239000000243 solution Substances 0.000 claims description 62
- 238000002360 preparation method Methods 0.000 claims description 61
- 150000003839 salts Chemical class 0.000 claims description 44
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 36
- 239000000796 flavoring agent Substances 0.000 claims description 35
- 239000003205 fragrance Substances 0.000 claims description 29
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 28
- 235000003599 food sweetener Nutrition 0.000 claims description 28
- 239000003765 sweetening agent Substances 0.000 claims description 28
- 239000007788 liquid Substances 0.000 claims description 27
- 239000007864 aqueous solution Substances 0.000 claims description 21
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 claims description 21
- 229910052939 potassium sulfate Inorganic materials 0.000 claims description 21
- 235000011151 potassium sulphates Nutrition 0.000 claims description 21
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 20
- 239000004376 Sucralose Substances 0.000 claims description 19
- 235000019408 sucralose Nutrition 0.000 claims description 19
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims description 19
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 18
- 235000011152 sodium sulphate Nutrition 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 16
- 210000003736 gastrointestinal content Anatomy 0.000 claims description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 15
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 15
- 235000013355 food flavoring agent Nutrition 0.000 claims description 14
- 239000004480 active ingredient Substances 0.000 claims description 12
- 239000007787 solid Substances 0.000 claims description 11
- 239000004471 Glycine Substances 0.000 claims description 10
- 235000005979 Citrus limon Nutrition 0.000 claims description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 8
- 238000002052 colonoscopy Methods 0.000 claims description 8
- 230000008030 elimination Effects 0.000 claims description 6
- 238000003379 elimination reaction Methods 0.000 claims description 6
- 150000008064 anhydrides Chemical class 0.000 claims description 4
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 3
- 239000001630 malic acid Substances 0.000 claims description 3
- 235000011090 malic acid Nutrition 0.000 claims description 3
- 235000019204 saccharin Nutrition 0.000 claims description 3
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims description 3
- 229940081974 saccharin Drugs 0.000 claims description 3
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 claims description 3
- 239000000892 thaumatin Substances 0.000 claims description 2
- 235000010436 thaumatin Nutrition 0.000 claims description 2
- 244000248349 Citrus limon Species 0.000 claims 1
- 235000002639 sodium chloride Nutrition 0.000 description 38
- 238000012360 testing method Methods 0.000 description 29
- 230000000694 effects Effects 0.000 description 22
- 239000000203 mixture Substances 0.000 description 22
- 235000019634 flavors Nutrition 0.000 description 21
- 238000009472 formulation Methods 0.000 description 20
- 239000008213 purified water Substances 0.000 description 19
- 238000001356 surgical procedure Methods 0.000 description 16
- 235000019658 bitter taste Nutrition 0.000 description 13
- 235000019640 taste Nutrition 0.000 description 13
- YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 description 12
- 238000011156 evaluation Methods 0.000 description 11
- 230000001953 sensory effect Effects 0.000 description 11
- ILJOYZVVZZFIKA-UHFFFAOYSA-M sodium;1,1-dioxo-1,2-benzothiazol-3-olate;hydrate Chemical compound O.[Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 ILJOYZVVZZFIKA-UHFFFAOYSA-M 0.000 description 11
- 235000013361 beverage Nutrition 0.000 description 10
- 244000269722 Thea sinensis Species 0.000 description 9
- 235000019643 salty taste Nutrition 0.000 description 9
- 244000131522 Citrus pyriformis Species 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 8
- -1 for example Substances 0.000 description 8
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 8
- 239000004299 sodium benzoate Substances 0.000 description 8
- 235000010234 sodium benzoate Nutrition 0.000 description 8
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 7
- 244000183278 Nephelium litchi Species 0.000 description 7
- 235000015742 Nephelium litchi Nutrition 0.000 description 7
- 229960003511 macrogol Drugs 0.000 description 7
- 159000000000 sodium salts Chemical class 0.000 description 7
- 240000000560 Citrus x paradisi Species 0.000 description 6
- 241000792859 Enema Species 0.000 description 6
- 229910052788 barium Inorganic materials 0.000 description 6
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 6
- 239000007920 enema Substances 0.000 description 6
- 229940095399 enema Drugs 0.000 description 6
- 230000002262 irrigation Effects 0.000 description 6
- 238000003973 irrigation Methods 0.000 description 6
- 231100000716 Acceptable daily intake Toxicity 0.000 description 5
- 239000002202 Polyethylene glycol Substances 0.000 description 5
- 150000001447 alkali salts Chemical class 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 239000003755 preservative agent Substances 0.000 description 5
- 235000019600 saltiness Nutrition 0.000 description 5
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 235000011941 Tilia x europaea Nutrition 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 238000010878 colorectal surgery Methods 0.000 description 4
- 238000011086 high cleaning Methods 0.000 description 4
- 239000004571 lime Substances 0.000 description 4
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 235000010358 acesulfame potassium Nutrition 0.000 description 3
- 229960004998 acesulfame potassium Drugs 0.000 description 3
- 239000000619 acesulfame-K Substances 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 230000029142 excretion Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 206010013911 Dysgeusia Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 159000000011 group IA salts Chemical class 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229960005336 magnesium citrate Drugs 0.000 description 2
- 235000002538 magnesium citrate Nutrition 0.000 description 2
- 239000004337 magnesium citrate Substances 0.000 description 2
- WRUGWIBCXHJTDG-UHFFFAOYSA-L magnesium sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Mg+2].[O-]S([O-])(=O)=O WRUGWIBCXHJTDG-UHFFFAOYSA-L 0.000 description 2
- 229940061634 magnesium sulfate heptahydrate Drugs 0.000 description 2
- LPUQAYUQRXPFSQ-DFWYDOINSA-M monosodium L-glutamate Chemical compound [Na+].[O-]C(=O)[C@@H](N)CCC(O)=O LPUQAYUQRXPFSQ-DFWYDOINSA-M 0.000 description 2
- 235000013923 monosodium glutamate Nutrition 0.000 description 2
- 239000004223 monosodium glutamate Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- PLSARIKBYIPYPF-UHFFFAOYSA-H trimagnesium dicitrate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O PLSARIKBYIPYPF-UHFFFAOYSA-H 0.000 description 2
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 235000004936 Bromus mango Nutrition 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 150000000996 L-ascorbic acids Chemical class 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 240000007228 Mangifera indica Species 0.000 description 1
- 235000014826 Mangifera indica Nutrition 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 235000009184 Spondias indica Nutrition 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 241000234568 Thaumatococcus Species 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 210000001815 ascending colon Anatomy 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 239000007958 cherry flavor Substances 0.000 description 1
- 239000008370 chocolate flavor Substances 0.000 description 1
- 239000012459 cleaning agent Substances 0.000 description 1
- 239000008373 coffee flavor Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- CDNAUIUELRAXBC-UHFFFAOYSA-L disodium sulfate tetrahydrate Chemical compound O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O CDNAUIUELRAXBC-UHFFFAOYSA-L 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000019605 sweet taste sensations Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
Description
本発明は、医薬組成物に関する。さらに詳しくは、本発明は、腸管内容物の排除のために用いられる医薬組成物に関する。 The present invention relates to pharmaceutical compositions. More specifically, the present invention relates to pharmaceutical compositions used for the elimination of intestinal contents.
経口腸管洗浄剤は、大腸内視鏡検査やバリウム注腸Ｘ線検査や大腸手術の前処理として、腸管内容物を洗浄流去するために用いられる経口の薬剤である。 Oral bowel irrigation is an oral drug used to wash away the contents of the intestine as a pretreatment for colonoscopy, barium enema X-ray examination, and colorectal surgery.
経口腸管洗浄剤として、たとえばクエン酸マグネシウムを有効成分として配合したもの（マグコロール（登録商標）、マグコロールＰ（登録商標））、塩化ナトリウム、塩化カリウム、炭酸水素ナトリウムおよび硫酸ナトリウムを有効成分として配合しマクロゴール（ポリエチレングリコール）４０００を添加したもの（ムーベン（登録商標）、ニフレック（登録商標））、塩化ナトリウム、塩化カリウム、硫酸ナトリウム、マクロゴール４０００およびアスコルビン酸類を配合したもの（モビプレップ（登録商標））が医療現場で用いられている。 As an oral bowel irrigation agent, for example, magnesium citrate as an active ingredient (magcorol (registered trademark), magcorol P (registered trademark)), sodium chloride, potassium chloride, sodium hydrogen carbonate and sodium sulfate are blended as active ingredients. Addition of Macrogol (polyethylene glycol) 4000 (Mouben (registered trademark), Nifrec (registered trademark)), sodium chloride, potassium chloride, sodium sulfate, Macrogol 4000 and ascorbic acids (Mobiprep (registered trademark)) ) Is used in the medical field.
クエン酸マグネシウムを配合し、マクロゴール４０００を配合しないものは、マクロゴール４０００を配合したものに比べ洗浄効果が劣っていると言われている。また、マクロゴール４０００を配合したものは、洗浄効果は良好であるが、マクロゴール（ポリエチレングリコール）に起因する油臭さや味の悪さにより飲用が容易ではない。 It is said that those containing magnesium citrate and not containing Macrogol 4000 are inferior in cleaning effect to those containing Macrogol 4000. Further, although the product containing Macrogol 4000 has a good cleaning effect, it is not easy to drink due to the oily odor and bad taste caused by macrogol (polyethylene glycol).
一方、マクロゴール４０００を配合せず、洗浄効果が高い経口腸管洗浄剤として、硫酸塩（硫酸ナトリウム、硫酸カリウムおよび硫酸マグネシウム）を有効成分として配合するものが提案されているが、その塩濃度の高さ故、塩味等のマスキングとしてスクラロース等の甘味料が配合されている（特許文献１の実施例２、表５および表６参照）。 On the other hand, as an oral intestinal cleaning agent having a high cleaning effect without blending Macrogol 4000, one containing sulfate (sodium sulfate, potassium sulfate and magnesium sulfate) as an active ingredient has been proposed, but the salt concentration thereof Due to its height, a sweetener such as sucralose is blended as a mask for saltiness and the like (see Example 2, Table 5 and Table 6 of Patent Document 1).
日本におけるスクラロースの一日摂取許容量は、１５ｍｇ／ｋｇ体重（平均体重５８．６ｋｇとすると、０．８７９ｇ／人／日）である（厚生労働省「マーケットバスケット方式による年齢層別食品添加物の一日摂取量の調査」の「甘味料」調査結果）。しかしながら、特許文献１に記載の経口腸管洗浄剤では、日本における一日摂取許容量を遥かに超える量（２．１６〜２．２４ｇ／日）のスクラロースが用いられる。 The acceptable daily intake of sucralose in Japan is 15 mg / kg body weight (0.879 g / person / day when the average body weight is 58.6 kg) (Ministry of Health, Labor and Welfare "One of the food additives by age group by the market basket method". Results of the "Sweetener" survey in the "Survey on Acceptable Daily Intake"). However, in the oral bowel irrigation agent described in Patent Document 1, sucralose in an amount (2.16 to 2.24 g / day) far exceeding the acceptable daily intake in Japan is used.
本発明は、かかる従来技術の現状に鑑み創案されたものであり、マクロゴール（ポリエチレングリコール）を配合せず、洗浄効果の高い硫酸塩を有効成分とし、多量のスクラロースに頼らずに塩味や苦味を低減する経口腸管洗浄剤の提供を目的とするものである。また、本発明は、希釈の必要がなく、容量を低減した経口腸管洗浄剤の提供を目的とするものである。 The present invention was devised in view of the current state of the prior art, and contains sulfate, which has a high cleaning effect, as an active ingredient without blending macrogol (polyethylene glycol), and has a salty taste and bitterness without relying on a large amount of scullose. The purpose is to provide an oral bowel irrigation agent that reduces the amount of bitterness. Another object of the present invention is to provide an oral bowel irrigation agent having a reduced volume without the need for dilution.
本発明者らは、上記目的を達成するために鋭意検討した結果、特定の硫酸塩を有効成分として配合したものにおいて、タウマチン又はその塩を甘味を感じない程度の量で配合することによって、多量のスクラロースを配合しなくても塩味や苦味を持続的に低減でき、容易に服用できることを見出し、本発明を完成した。 As a result of diligent studies to achieve the above object, the present inventors have made a large amount of taumatin or a salt thereof in a mixture containing a specific sulfate as an active ingredient in an amount not to be sweetened. The present invention has been completed by finding that the salty taste and bitterness can be continuously reduced and the drug can be easily taken without adding sucralose.
すなわち、本発明は、以下の（１）〜（１１）の構成を有するものである。
（１）硫酸ナトリウム、硫酸カリウムおよび硫酸マグネシウムを有効成分として含有する医薬組成物において、甘味料としてタウマチンまたはその塩を含有することを特徴とする医薬組成物。
（２）甘味料として、さらにスクラロースを含有することを特徴とする（１）に記載の医薬組成物。
（３）腸管内容物の排除のために用いられることを特徴とする（１）または（２）に記載の医薬組成物。
（４）大腸内視鏡検査の前処置における腸管内容物の排除のために経口的に用いられることを特徴とする（１）または（２）に記載の医薬組成物。
（５）甘味料として、さらにサッカリンまたはその塩を含有することを特徴とする（１）または（２）に記載の医薬組成物。
（６）さらに、矯味料としてグリシンまたはその塩、リンゴ酸またはその塩およびクエン酸またはその塩を含有することを特徴とする（１）または（２）に記載の医薬組成物。
（７）さらに、香料としてレモン香料を含有することを特徴とする（１）または（２）に記載の医薬組成物。
（８）水溶液剤の形態であることを特徴とする（１）または（２）に記載の医薬組成物。
（９）水溶液剤中のタウマチンまたはその塩の濃度が０．２ｍｇ／ｌ以上１０ｍｇ／ｌ以下であることを特徴とする（８）に記載の医薬組成物。
（１０）硫酸ナトリウム、硫酸カリウムおよび硫酸マグネシウムを有効成分として含有する医薬組成物であって、甘味料としてタウマチンまたはその塩を含有する医薬組成物を対象に投与することを特徴とする腸管内容物の排除方法。
（１１）腸管内容物の排除のための、硫酸ナトリウム、硫酸カリウムおよび硫酸マグネシウムを有効成分として含有する医薬組成物であって、甘味料としてタウマチンまたはその塩を含有する医薬組成物の使用。That is, the present invention has the following configurations (1) to (11).
(1) A pharmaceutical composition containing sodium sulfate, potassium sulfate and magnesium sulfate as active ingredients, which contains taumatin or a salt thereof as a sweetener.
(2) The pharmaceutical composition according to (1), which further contains sucralose as a sweetener.
(3) The pharmaceutical composition according to (1) or (2), which is used for eliminating intestinal contents.
(4) The pharmaceutical composition according to (1) or (2), which is used orally for the elimination of intestinal contents in the pretreatment of colonoscopy.
(5) The pharmaceutical composition according to (1) or (2), which further contains saccharin or a salt thereof as a sweetener.
(6) The pharmaceutical composition according to (1) or (2), further containing glycine or a salt thereof, malic acid or a salt thereof and citric acid or a salt thereof as a flavoring agent.
(7) The pharmaceutical composition according to (1) or (2), which further contains a lemon fragrance as a fragrance.
(8) The pharmaceutical composition according to (1) or (2), which is in the form of an aqueous solution.
(9) The pharmaceutical composition according to (8), wherein the concentration of taumatin or a salt thereof in the aqueous solution is 0.2 mg / l or more and 10 mg / l or less.
(10) An intestinal content which is a pharmaceutical composition containing sodium sulfate, potassium sulfate and magnesium sulfate as active ingredients, wherein the pharmaceutical composition containing taumatin or a salt thereof as a sweetener is administered to a subject. Elimination method.
(11) Use of a pharmaceutical composition containing sodium sulfate, potassium sulfate and magnesium sulfate as active ingredients for eliminating intestinal contents, and containing taumatin or a salt thereof as a sweetener.
本発明の医薬組成物は、経口腸管洗浄剤として特定の硫酸塩を有効成分として含有し、かかる成分の塩味や苦味を低減するためにタウマチンまたはその塩を配合しているので、腸管内容物の排除のための高い洗浄効果を有しながら、塩味や苦味をほとんど感じずに容易に服用することができる。 Since the pharmaceutical composition of the present invention contains a specific sulfate as an active ingredient as an oral bowel irrigation agent and contains taumatin or a salt thereof in order to reduce the salty taste and bitterness of such ingredients, the intestinal contents. It can be easily taken with almost no salty or bitter taste while having a high cleaning effect for elimination.
本発明の医薬組成物は、硫酸ナトリウム、硫酸カリウムおよび硫酸マグネシウムを有効成分として含有し、甘味料としてタウマチンまたはその塩を含有することを特徴とするものである。 The pharmaceutical composition of the present invention is characterized by containing sodium sulfate, potassium sulfate and magnesium sulfate as active ingredients, and taumatin or a salt thereof as a sweetener.
本発明で用いる硫酸ナトリウムおよび硫酸マグネシウムは、無水物であっても水和物であってもよい。 The sodium sulfate and magnesium sulfate used in the present invention may be anhydrous or hydrated.
本発明で用いるタウマチン（Ｔｈａｕｍａｔｉｎ）としては、Ｔｈａｕｍａｔｏｃｏｃｃｕｓ ｄａｎｉｅｌｉの種子から得られる２０７個のアミノ酸からなるタンパク質が挙げられるが、他の原料から得られたものであってもよく、また遺伝子工学的に調製されたものであってもよい。タウマチンの塩としては、たとえば酒石酸等の有機酸との塩（薬理学的に許容されうる塩）が挙げられる。 Examples of Thaumatin used in the present invention include proteins consisting of 207 amino acids obtained from the seeds of Thaumatococcus danieli, but they may be obtained from other raw materials and are genetically engineered. It may be the one that has been done. Examples of the salt of taumatin include a salt with an organic acid such as tartaric acid (a pharmacologically acceptable salt).
本発明の医薬組成物は、甘味料としてタウマチンまたはその塩に加えて、スクラロースを含有することができる。但し、スクラロースの配合量は、一日摂取許容量の上限以下、すなわち、一日当たり０．８７９ｇ以下となるようにすることが好ましい。また、本発明の医薬組成物には、タウマチンまたはその塩およびスクラロースに加えて、他の甘味料、たとえばサッカリンまたはその塩（例、ナトリウム塩などの薬理学的に許容されうるアルカリ塩）またはその水和物、アスパルテーム、アセスルファムカリウムを配合してもよい。 The pharmaceutical composition of the present invention can contain sucralose as a sweetener in addition to taumatin or a salt thereof. However, the blending amount of sucralose is preferably not more than the upper limit of the acceptable daily intake, that is, 0.879 g or less per day. Further, in addition to taumatin or a salt thereof and sucralose, the pharmaceutical composition of the present invention includes other sweeteners such as saccharin or a salt thereof (eg, a pharmacologically acceptable alkaline salt such as a sodium salt) or a salt thereof. A hydrate, aspartame, and acesulfame potassium may be blended.
また、本発明の医薬組成物には、上記の甘味料に加えて、矯味料、防腐剤、香料等を配合してもよい。 In addition to the above sweeteners, the pharmaceutical composition of the present invention may contain a flavoring agent, a preservative, a flavoring agent, or the like.
矯味料は、たとえば塩味や苦味の低減、酸味の付与のために配合される。矯味料としては、たとえばグリシンまたはその塩（例、塩酸などの酸との薬理学的に許容されうる塩）、アラニンまたはその塩（例、塩酸などの酸との薬理学的に許容されうる塩）、グルタミン酸またはその塩（例、ナトリウム塩などの薬理学的に許容されうるアルカリ塩）等のアミノ酸類、たとえばリンゴ酸またはその塩（例、ナトリウム塩などの薬理学的に許容されうるアルカリ塩）、クエン酸またはその塩（例、ナトリウム塩などの薬理学的に許容されうるアルカリ塩）もしくは水和物（クエン酸一水和物）、アスコルビン酸またはその塩（例、ナトリウム塩などの薬理学的に許容されうるアルカリ塩）、乳酸またはその塩（例、ナトリウム塩などの薬理学的に許容されうるアルカリ塩）等の有機酸類が挙げられる。 The flavoring agent is added, for example, to reduce saltiness and bitterness, and to impart sourness. Examples of the flavoring agent include glycine or a salt thereof (eg, a pharmacologically acceptable salt with an acid such as hydrochloric acid), alanine or a salt thereof (eg, a pharmacologically acceptable salt with an acid such as hydrochloric acid). ), Glutamic acid or salts thereof (eg, pharmacologically acceptable alkali salts such as sodium salts), such as malic acid or salts thereof (eg, pharmacologically acceptable alkali salts such as sodium salts). ), Citric acid or salts thereof (eg, pharmacologically acceptable alkali salts such as sodium salts) or hydrates (citrate monohydrate), ascorbic acid or salts thereof (eg, drugs such as sodium salts) Examples thereof include organic acids such as physically acceptable alkali salts), lactic acid or salts thereof (eg, pharmacologically acceptable alkali salts such as sodium salts).
防腐剤としては、たとえば安息香酸またはその塩（例、ナトリウム塩などの薬理学的に許容されうるアルカリ塩）が挙げられる。 Preservatives include, for example, benzoic acid or salts thereof (eg, pharmacologically acceptable alkaline salts such as sodium salts).
香料としては、たとえばレモン香料、グレープフルーツ香料、グレープ香料、オレンジ香料、チェリー香料、フルーツミックス香料、マンゴ香料、ライチ香料、チョコレート香料、コーヒー香料、ウメ香料、ライム香料、シュガー香料、ミルク香料等が挙げられ、なかでもレモン香料、グレープフルーツ香料、ライチ香料およびライム香料が好ましく、レモン香料およびグレープフルーツ香料がさらに好ましい。 Examples of flavors include lemon flavors, grapefruit flavors, grape flavors, orange flavors, cherry flavors, fruit mix flavors, mango flavors, lychee flavors, chocolate flavors, coffee flavors, plum flavors, lime flavors, sugar flavors, milk flavors, etc. Among them, lemon flavor, grapefruit flavor, lychee flavor and lime flavor are preferable, and lemon flavor and grapefruit flavor are more preferable.
本発明の医薬組成物は、固形剤または液剤であることができるが、液剤が好ましく、なかでも水溶液剤がより好ましい。固形剤として提供される場合には、固形剤を用時水に溶解して用いればよい。 The pharmaceutical composition of the present invention can be a solid agent or a liquid agent, but a liquid agent is preferable, and an aqueous solution agent is more preferable. When provided as a solid agent, the solid agent may be dissolved in water before use.
本発明の医薬組成物は、それ自体公知の方法に従い、調製することができる。たとえば、水溶液剤としての本発明の医薬組成物は、硫酸塩（硫酸ナトリウム、硫酸カリウムおよび硫酸マグネシウム）とタウマチンまたはその塩等の他の成分とを精製水に添加して溶解することによって調製できる。好ましくは、硫酸塩を精製水に添加して溶解し、必要により溶解液にスクラロースおよび他の甘味料、矯味料および防腐剤を添加して溶解した後、加温殺菌し、冷却した後、除菌ろ過した熱に弱い成分（例、タウマチンまたはその塩、香料）を添加して混合することによって調製できる。当該調製液は、液量を調整したのち、ボトル等の容器に充填し施栓する。 The pharmaceutical composition of the present invention can be prepared according to a method known per se. For example, the pharmaceutical composition of the present invention as an aqueous solution can be prepared by adding and dissolving a sulfate (sodium sulfate, potassium sulfate and magnesium sulfate) and other components such as taumatin or a salt thereof in purified water. .. Preferably, sulfate is added to purified water to dissolve it, and if necessary, sucralose and other sweeteners, flavoring agents and preservatives are added to dissolve the solution, which is then sterilized by heating, cooled and then removed. It can be prepared by adding and mixing a heat-sensitive component (eg, taumatin or a salt thereof, a fragrance) filtered by bacteria. After adjusting the amount of the prepared liquid, the prepared liquid is filled in a container such as a bottle and capped.
本発明の医薬組成物は、用時での溶解や希釈の手間や、その際生じる過誤の可能性を考慮すると、用時に希釈の必要がない水溶液剤が最も好ましい。希釈せずに用いる際の液剤の容量、希釈して用いる場合の希釈液の容量および固形剤を水に溶解して用いる際の容量（すなわち、大腸内視鏡検査の前処置、バリウム注腸Ｘ線検査の前処置または大腸手術の前処置として用いる医薬組成物全量の容量）は、通常７００ｍｌ〜１２００ｍｌが好ましく、９００ｍｌ〜１０００ｍｌがより好ましい。 The pharmaceutical composition of the present invention is most preferably an aqueous solution which does not need to be diluted at the time of use, in consideration of the trouble of dissolving and diluting at the time of use and the possibility of error occurring at that time. Volume of solution when used undiluted, volume of diluted solution when used diluted and volume when solids are dissolved in water (ie, pretreatment for colonoscopy, barium enema X The volume of the total amount of the pharmaceutical composition used as a pretreatment for line examination or a pretreatment for colorectal surgery) is usually preferably 700 ml to 1200 ml, more preferably 900 ml to 1000 ml.
後述のとおり、本発明の医薬組成物は、検査（大腸内視鏡検査、バリウム注腸Ｘ線検査）や手術（大腸手術）の前日および当日の２回に分けて投与することもできるように、一容器中の医薬組成物の容量としては、通常３５０ｍｌ〜６００ｍｌが好ましく、４５０ｍｌ〜５００ｍｌがより好ましい。 As will be described later, the pharmaceutical composition of the present invention can be administered in two divided doses on the day before and on the day of examination (colonoscopy, barium enema X-ray examination) and surgery (colon surgery). The volume of the pharmaceutical composition in one container is usually preferably 350 ml to 600 ml, more preferably 450 ml to 500 ml.
腸管内容物の排出をより早くかつより効率的に達成するため及び腸管からの水分排出による脱水症を予防するため、本発明の医薬組成物を投与した後、投与した医薬組成物の容量の約倍量の水またはお茶等の飲料を服用することが好ましい。 In order to achieve faster and more efficient excretion of intestinal contents and to prevent dehydration due to water excretion from the intestinal tract, after administration of the pharmaceutical composition of the present invention, about the volume of the administered pharmaceutical composition It is preferable to take twice the amount of water or a beverage such as tea.
本発明の医薬組成物は、毒性が低く、腸管内容物の排除を目的として、検査（大腸内視鏡検査、バリウム注腸Ｘ線検査）を受ける被験者または手術（大腸手術）を受ける患者などの対象に、検査や手術の前に経口的に投与することができる。 The pharmaceutical composition of the present invention is less toxic and is used by subjects undergoing examination (colonoscopy, barium enema X-ray examination) or patients undergoing surgery (colon surgery) for the purpose of eliminating intestinal contents. Can be given orally to the subject prior to examination or surgery.
本発明の医薬組成物の各成分は、一容器当たりたとえば以下に示す量が好ましいが、投与中に腸管内容物の排除が完了した場合は、投与量を減量できる。また、検査や手術の前日および当日の２回に分けて投与する場合や、当日一日で二容器分を投与する場合、本発明の医薬組成物の各成分は二容器分の量、すなわち以下に示す量の倍量を用いて調製してもよい。 Each component of the pharmaceutical composition of the present invention is preferably in the amount shown below, for example, per container, but the dose can be reduced if the elimination of the intestinal contents is completed during administration. In addition, when the dose is divided into two doses on the day before and on the day of examination or surgery, or when two containers are administered on the same day, each component of the pharmaceutical composition of the present invention is in the amount of two containers, that is, the following. It may be prepared using a double amount of the amount shown in.
硫酸ナトリウムの量（一容器当たり）
無水硫酸ナトリウムを用いる場合、１４．０〜２１．０ｇが好ましく、１５．７〜１９．３ｇがさらに好ましい。水和物を用いる場合には、硫酸ナトリウム量として前記の量を用いればよい。たとえば硫酸ナトリウム１０水和物を用いる場合、３１．７〜４７．７ｇが好ましく、３５．８〜４３．８ｇがさらに好ましい。水溶液剤中の硫酸ナトリウムの濃度は（無水物として換算して）２９．１〜４３．８ｇ/ｌが好ましく、３２．８〜４０．２ｇ/ｌがさらに好ましい。Amount of sodium sulfate (per container)
When anhydrous sodium sulfate is used, 14.0 to 21.0 g is preferable, and 15.7 to 19.3 g is more preferable. When a hydrate is used, the above amount may be used as the amount of sodium sulfate. For example, when sodium sulfate tetrahydrate is used, 31.7 to 47.7 g is preferable, and 35.8 to 43.8 g is more preferable. The concentration of sodium sulfate in the aqueous solution is preferably 29.1 to 43.8 g / l (converted as an anhydride), more preferably 32.8 to 40.2 g / l.
硫酸カリウムの量（一容器当たり）
２．５〜３．８ｇが好ましく、２．８〜３．５ｇがさらに好ましい。水溶液剤中の硫酸カリウムの濃度は５．２〜７．９ｇ/ｌが好ましく、５．８〜７．２ｇ/ｌがさらに好ましい。Amount of potassium sulfate (per container)
2.5 to 3.8 g is preferable, and 2.8 to 3.5 g is more preferable. The concentration of potassium sulfate in the aqueous solution is preferably 5.2 to 7.9 g / l, more preferably 5.8 to 7.2 g / l.
硫酸マグネシウムの量（一容器当たり）
無水硫酸マグネシウムを用いる場合、１．２〜２．０ｇが好ましく、１．４〜１．８ｇがさらに好ましい。水和物を用いる場合には、硫酸マグネシウム量として前記の量を用いればよい。たとえば硫酸マグネシウム７水和物を用いる場合、２．６〜３．９ｇが好ましく、２．９〜３．６ｇがさらに好ましい。水溶液剤中の硫酸マグネシウムの濃度は（無水物として換算して）２．６〜４．０ｇ/ｌが好ましく、２．９〜３．７ｇ/ｌがさらに好ましい。Amount of magnesium sulfate (per container)
When anhydrous magnesium sulfate is used, 1.2 to 2.0 g is preferable, and 1.4 to 1.8 g is more preferable. When a hydrate is used, the above amount may be used as the amount of magnesium sulfate. For example, when magnesium sulfate heptahydrate is used, 2.6 to 3.9 g is preferable, and 2.9 to 3.6 g is more preferable. The concentration of magnesium sulfate in the aqueous solution is preferably 2.6 to 4.0 g / l (converted as an anhydride), and more preferably 2.9 to 3.7 g / l.
タウマチンまたはその塩の量（一容器当たり）
スクラロースの量にもよるが、０．１〜５ｍｇが好ましく、０．５〜３ｍｇがより好ましく、０．８〜１．２ｍｇがさらに好ましく、０．９〜１．１ｍｇが最も好ましい。タウマチンまたはその塩に由来する甘味を感じない程度のタウマチンまたはその塩の量（濃度）としては、水溶液剤中、約０．２ｍｇ／ｌ以上、好ましくは約０．８ｍｇ／ｌ以上、約１０ｍｇ／ｌ以下、好ましくは約８ｍｇ／ｌ以下、さらに好ましくは約６ｍｇ／ｌ以下である。また、上記の硫酸ナトリウム、硫酸カリウムおよび硫酸マグネシウムの合計量１重量部（無水物として換算して）に対して、タウマチンまたはその塩は好ましくは４．４×１０−６〜２．３×１０−４重量部であり、さらに好ましくは２．２×１０−５〜１．４×１０−４重量部である。Amount of taumatin or its salt (per container)
Although it depends on the amount of sucralose, 0.1 to 5 mg is preferable, 0.5 to 3 mg is more preferable, 0.8 to 1.2 mg is further preferable, and 0.9 to 1.1 mg is most preferable. The amount (concentration) of taumatin or a salt thereof to the extent that the sweetness derived from taumatin or a salt thereof is not felt is about 0.2 mg / l or more, preferably about 0.8 mg / l or more, about 10 mg / l in the aqueous solution. It is l or less, preferably about 8 mg / l or less, and more preferably about 6 mg / l or less. Further, with respect to 1 part by weight (converted as an anhydride) of the total amount of sodium sulfate, potassium sulfate and magnesium sulfate described above, taumatin or a salt thereof is preferably 4.4 × 10 -6 to 2.3 × 10. It is -4 parts by weight, more preferably 2.2 × 10 -5 to 1.4 × 10 -4 parts by weight.
スクラロースの量（一容器当たり）
本発明の医薬組成物は、２容器分使用しても一日摂取許容量以下（たとえば、０．８ｇ／日以下、好ましくは０．６ｇ／日以下、さらに好ましくは０．４ｇ／日以下）であることが望ましく、また他の甘味料（たとえば、サッカリンナトリウム）の量にもよるが、０．１２〜０．１８ｇが好ましく、０．１４〜０．１７ｇがさらに好ましい。水溶液剤中のスクラロースの濃度は０．２４〜０．３８ｇ/ｌが好ましく、０．２７〜０．３５ｇ/ｌがさらに好ましい。上記の硫酸ナトリウム、硫酸カリウムおよび硫酸マグネシウムの合計量１重量部（無水物として換算して）に対して、スクラロースは好ましくは５．４×１０−３〜８．１×１０−３重量部であり、さらに好ましくは６．３×１０−３〜７．７×１０−３重量部である。Amount of sucralose (per container)
The pharmaceutical composition of the present invention has an acceptable daily intake or less (for example, 0.8 g / day or less, preferably 0.6 g / day or less, more preferably 0.4 g / day or less) even when used in two containers. It is desirable that the amount is 0.12 to 0.18 g, more preferably 0.14 to 0.17 g, depending on the amount of other sweeteners (for example, sodium saccharin). The concentration of sucralose in the aqueous solution is preferably 0.24 to 0.38 g / l, more preferably 0.27 to 0.35 g / l. With respect to 1 part by weight (converted as anhydrous) of the total amount of sodium sulfate, potassium sulfate and magnesium sulfate described above, sclarose is preferably 5.4 × 10 -3 to 8.1 × 10 -3 parts by weight. Yes, more preferably 6.3 × 10 -3 to 7.7 × 10 -3 parts by weight.
本発明の医薬組成物における他の成分（例、甘味料、矯味料、防腐剤、香料）はその種類によって量が異なるが、他の成分の種類およびその量としては、一容器当たり、たとえば以下の表に示すものが好ましい。また、本発明の医薬組成物を検査や手術の前日および当日の２回に分けて投与する場合や、当日一日で二容器分を投与する場合、他の成分は各々、上記の本発明の医薬組成物の各成分と同様、二容器分の量を用いて調製することができる。また、これらの成分の水溶液剤中の濃度は、たとえば以下の表に示すものが好ましい。 The amount of other ingredients (eg, sweeteners, flavoring agents, preservatives, flavors) in the pharmaceutical composition of the present invention varies depending on the type, but the types and amounts of other ingredients are as follows, for example, per container. The one shown in the table of is preferable. In addition, when the pharmaceutical composition of the present invention is administered in two divided doses on the day before and on the day before and on the day of examination or surgery, or when two containers are administered on the same day, the other components of the present invention are described above. Similar to each component of the pharmaceutical composition, it can be prepared using the amount of two containers. The concentrations of these components in the aqueous solution are preferably those shown in the table below, for example.
甘味料としてアセスルファムカリウムを用いる場合は、他の成分の種類や量によっても異なるが、一容器当たり、０．０３１〜０．０４７ｇが好ましく、０．０３５〜０．０４３ｇがさらに好ましい。水溶液剤中のアセスルファムカリウムの濃度は０．０６４〜０．０９８ｇ/ｌが好ましく、０．０７３〜０．０９０ｇ/ｌがさらに好ましい。 When acesulfame potassium is used as a sweetener, it is preferably 0.031 to 0.047 g, more preferably 0.035 to 0.043 g per container, although it depends on the type and amount of other components. The concentration of acesulfame potassium in the aqueous solution is preferably 0.064 to 0.098 g / l, more preferably 0.073 to 0.090 g / l.
矯味料としてグルタミン酸ナトリウムを用いる場合は、他の成分の種類や量によっても異なるが、一容器当たり、０．０８〜０．１２ｇが好ましく、０．０９〜０．１１ｇがさらに好ましい。水溶液剤中のグルタミン酸ナトリウムの濃度は０．１７〜０．２５ｇ/ｌが好ましく、０．１８〜０．２３ｇ/ｌがさらに好ましい。矯味料としてアラニンを用いる場合は、他の成分の種類や量によっても異なるが、一容器当たり、０．４８〜０．７２ｇが好ましく、０．５４〜０．６６ｇがさらに好ましい。水溶液剤中のアラニンの濃度は１．０〜１．５ｇ/ｌが好ましく、１．１〜１．４ｇ/ｌがさらに好ましい。 When monosodium glutamate is used as a flavoring agent, it is preferably 0.08 to 0.12 g, more preferably 0.09 to 0.11 g per container, although it depends on the type and amount of other components. The concentration of monosodium glutamate in the aqueous solution is preferably 0.17 to 0.25 g / l, more preferably 0.18 to 0.23 g / l. When alanine is used as a flavoring agent, it is preferably 0.48 to 0.72 g, more preferably 0.54 to 0.66 g per container, although it depends on the type and amount of other components. The concentration of alanine in the aqueous solution is preferably 1.0 to 1.5 g / l, more preferably 1.1 to 1.4 g / l.
本発明の医薬組成物には、添加剤としてマクロゴール（ポリエチレングリコール）を用いてもよいが、甘味を感じない程度の量のタウマチンまたはその塩ではマクロゴールに起因する油臭さや味の悪さを十分に緩和することが難しく、また本発明の医薬組成物に含まれる硫酸塩で腸管の十分な洗浄力が得られるため、マクロゴールを用いないことが好ましい。 Macrogol (polyethylene glycol) may be used as an additive in the pharmaceutical composition of the present invention, but taumatin or a salt thereof in an amount that does not give a sweet taste causes an oily odor or bad taste due to macrogol. It is preferable not to use macrogol because it is difficult to sufficiently relax and the sulfate contained in the pharmaceutical composition of the present invention can provide sufficient detergency for the intestinal tract.
本発明の医薬組成物は通常、検査または手術の前日と当日に分けて投与するか、検査または手術の当日に投与する。 The pharmaceutical composition of the present invention is usually administered separately on the day before and on the day of examination or surgery, or on the day of examination or surgery.
検査または手術の前日と当日に分けて投与する場合、検査または手術の前日の夜に、通常成人（体重約６０ｋｇ）には上記一容器分の医薬組成物を約３０分かけて投与する。医薬組成物を投与した後、医薬組成物の倍量の水またはお茶等の飲料を約６０分かけて飲用する。 When the administration is divided into the day before the test or surgery and the day before the test or surgery, the above-mentioned one container of the pharmaceutical composition is usually administered to an adult (body weight of about 60 kg) over about 30 minutes on the night before the test or surgery. After administering the pharmaceutical composition, drink twice as much water or a beverage such as tea as the pharmaceutical composition over about 60 minutes.
検査または手術の当日には、検査または手術の開始予定時刻の約３時間以上前から医薬組成物の投与を開始し、通常成人には上記一容器分の医薬組成物を約３０分かけて投与する。医薬組成物を投与した後、医薬組成物の倍量の水またはお茶等の飲料を飲用する。ただし、排泄物が透明になった時点で医薬組成物の投与を終了し、その時点までに投与した医薬組成物の倍量の水またはお茶等の飲料を飲用する。 On the day of the test or surgery, administration of the pharmaceutical composition is started about 3 hours or more before the scheduled start time of the test or surgery, and usually, the above-mentioned container of the pharmaceutical composition is administered to adults over about 30 minutes. To do. After administering the pharmaceutical composition, drink twice as much water or a beverage such as tea as the pharmaceutical composition. However, when the excrement becomes transparent, the administration of the pharmaceutical composition is terminated, and a beverage such as water or tea, which is twice the amount of the pharmaceutical composition administered up to that point, is drunk.
本発明の医薬組成物を当日一日で投与する場合、検査または手術の開始予定時刻の約３時間以上前から医薬組成物の投与を開始し、通常成人には上記一容器分の医薬組成物を約３０分かけて投与する。医薬組成物を投与した後、医薬組成物の倍量の水またはお茶等の飲料を約６０分かけて飲用する。ただし、排泄物が透明になった時点で医薬組成物の投与を終了し、その時点までに投与した医薬組成物の倍量の水またはお茶等の飲料を飲用する。 When the pharmaceutical composition of the present invention is administered on the same day, administration of the pharmaceutical composition is started about 3 hours or more before the scheduled start time of the examination or surgery, and usually for adults, the above-mentioned one container of the pharmaceutical composition is administered. Is administered over about 30 minutes. After administering the pharmaceutical composition, drink twice as much water or a beverage such as tea as the pharmaceutical composition over about 60 minutes. However, when the excrement becomes transparent, the administration of the pharmaceutical composition is terminated, and a beverage such as water or tea, which is twice the amount of the pharmaceutical composition administered up to that point, is drunk.
逆に、排泄物が透明になっていない場合には、医薬組成物一容器分の半量を約１５分かけて追加投与し、その後、追加投与された医薬組成物の倍量の水またはお茶等の飲料を約３０分かけて飲用する。これを最大で２回繰り返すことができるが、排泄物が透明になった時点で医薬組成物の投与を終了し、その時点で追加投与した医薬組成物の倍量の水またはお茶等の飲料を飲用する。 On the contrary, when the excrement is not transparent, half the amount of one container of the pharmaceutical composition is additionally administered over about 15 minutes, and then double the amount of water or tea of the additionally administered pharmaceutical composition, etc. Drink the beverage for about 30 minutes. This can be repeated up to twice, but when the excrement becomes transparent, the administration of the pharmaceutical composition is terminated, and at that time, double the amount of the additionally administered pharmaceutical composition is given as a beverage such as water or tea. Drink.
本発明の医薬組成物を小児に投与する場合には、年齢や体重等に応じて、医薬組成物の投与量および水やお茶等の飲料の飲用量を減量してもよい。 When the pharmaceutical composition of the present invention is administered to a child, the dose of the pharmaceutical composition and the drinking dose of a beverage such as water or tea may be reduced according to age, body weight and the like.
本発明の医薬組成物は腸管の洗浄力、すなわち腸管内容物の排出能力が優れる。特に上行結腸での洗浄力が優れる。また、腸管内容物の排出までに要する時間が短く、したがって、検査や手術までに要する時間を短くできる。 The pharmaceutical composition of the present invention has an excellent intestinal detergency, that is, an ability to discharge intestinal contents. Especially excellent in detergency in the ascending colon. In addition, the time required for excretion of the intestinal contents is short, and therefore the time required for examination and surgery can be shortened.
さらに、本発明の医薬組成物を投与する際には、その投与後に水やその他の飲料を飲用するものの、医薬組成物の投与量が少ないことから、投与時の被験者または患者の負担が少なく、嘔吐等の副作用も少ない。 Further, when the pharmaceutical composition of the present invention is administered, water or other beverages are drunk after the administration, but the dose of the pharmaceutical composition is small, so that the burden on the subject or patient at the time of administration is small. There are few side effects such as vomiting.
本発明の医薬組成物は、マクロゴール（ポリエチレングリコール）を有効成分としないため、油臭さがない。また、タウマチンの配合により、塩味や苦味が低減されている。たとえば、後述の試験例１に示したとおり、甘味を感じない程度の少量のタウマチンを配合しても、硫酸塩の塩味や苦味を低減させるか、感じさせない。また、この塩味や苦味の低減は持続的であり、したがって本発明の医薬組成物は、上述のとおり約３０分間あるいはそれ以上の時間（約４５分間〜約６０分間）をかけて投与しても容易に服用できる。。また、本発明の医薬組成物は、好ましくは水溶液剤の形態であるので、さらに希釈する必要がなく、また、溶解液に溶解する必要もないことから、投与時の過誤の可能性が低い。 Since the pharmaceutical composition of the present invention does not contain macrogol (polyethylene glycol) as an active ingredient, it does not have an oily odor. In addition, saltiness and bitterness are reduced by blending taumatin. For example, as shown in Test Example 1 described later, even if a small amount of taumatin that does not feel sweetness is blended, the salty taste and bitterness of sulfate are reduced or not felt. In addition, this reduction in saltiness and bitterness is persistent, and therefore, the pharmaceutical composition of the present invention may be administered over a period of about 30 minutes or longer (about 45 minutes to about 60 minutes) as described above. Easy to take. .. Further, since the pharmaceutical composition of the present invention is preferably in the form of an aqueous solution, it does not need to be further diluted and does not need to be dissolved in a solution, so that there is a low possibility of error during administration.
従って、本発明の医薬組成物は、大腸内視鏡検査やバリウム注腸Ｘ線検査や大腸手術の前処理として、腸管内容物を洗浄流去するために被験者または患者に経口的に投与できる。 Therefore, the pharmaceutical composition of the present invention can be orally administered to a subject or patient to wash away the intestinal contents as a pretreatment for colonoscopy, barium enema X-ray examination and colorectal surgery.
以下に製剤例および試験例を示して本発明をさらに詳しく説明するが、本発明はこれらに限定されるものではない。 The present invention will be described in more detail below with reference to formulation examples and test examples, but the present invention is not limited thereto.
製剤例１
無水硫酸ナトリウム、硫酸カリウム、無水硫酸マグネシウムおよび安息香酸ナトリウム（防腐剤）を精製水に溶解したのち、タウマチンを加え、精製水で溶液の液量を調整し、以下の表に記載の比率の液剤（溶液）を調製した。 Formulation Example 1
After dissolving anhydrous sodium sulfate, potassium sulfate, anhydrous magnesium sulfate and sodium benzoate (preservative) in purified water, add taumatin, adjust the volume of the solution with purified water, and prepare the solution in the ratio shown in the table below. (Solution) was prepared.
製剤例２
無水硫酸ナトリウム、硫酸カリウム、無水硫酸マグネシウム、安息香酸ナトリウム、スクラロース、タウマチンおよびグリシンを精製水に溶解し、クエン酸水和物を加え、精製水で溶液の液量を調整し、以下の表３に示す比率の液剤（溶液）を調製した。 Preparation example 2
Dissolve anhydrous sodium sulfate, potassium sulfate, anhydrous magnesium sulfate, sodium benzoate, sucralose, taumatin and glycine in purified water, add citrate hydrate, and adjust the volume of the solution with purified water. Table 3 below. A liquid preparation (solution) having the ratio shown in 1 was prepared.
製剤例３（１）
無水硫酸ナトリウム、硫酸カリウム、無水硫酸マグネシウム、安息香酸ナトリウム、スクラロース、タウマチン、グリシンおよびクエン酸水和物を精製水に溶解し、アセスルファムカリウムを加え、精製水で溶液の液量を調整し，以下の表４に示す比率の液剤（溶液）を調製した。 Preparation Example 3 (1)
Dissolve anhydrous sodium sulfate, potassium sulfate, anhydrous magnesium sulfate, sodium benzoate, sclerose, taumatin, glycine and citrate hydrate in purified water, add acesulfam potassium, and adjust the volume of the solution with purified water. The solutions (solutions) having the ratios shown in Table 4 of the above were prepared.
製剤例３（２）
製剤例３（１）と同様に、以下の表５に示す比率の液剤（溶液）を調製した。 Preparation Example 3 (2)
In the same manner as in Preparation Example 3 (1), solutions (solutions) having the ratios shown in Table 5 below were prepared.
製剤例３（３）
製剤例３（１）と同様に、以下の表６に示す比率の液剤（溶液）を調製した。 Preparation Example 3 (3)
Similar to Preparation Example 3 (1), solutions (solutions) having the ratios shown in Table 6 below were prepared.
製剤例４
製剤例３（１）と同様に、以下の表７、表８、表９および表１０に示す比率の液剤（溶液）を調製した。 Preparation example 4
Similar to Formulation Example 3 (1), solutions (solutions) having the ratios shown in Tables 7, 8, 9, and 10 below were prepared.
製剤例５
無水硫酸ナトリウム、硫酸カリウム、無水硫酸マグネシウム、安息香酸ナトリウム、スクラロース、タウマチン、グリシン、ＤＬ−リンゴ酸およびサッカリンナトリウムを精製水に溶解し、クエン酸水和物を加え、精製水で溶液の液量を調整し、以下の表１１に示す比率の液剤（溶液）を調製した。 Formulation Example 5
Dissolve anhydrous sodium sulfate, potassium sulfate, anhydrous magnesium sulfate, sodium benzoate, sucralose, taumatin, glycine, DL-apple acid and sodium saccharin in purified water, add citric acid hydrate, and adjust the volume of the solution with purified water. After adjustment, liquid preparations (solutions) having the ratios shown in Table 11 below were prepared.
製剤例６
無水硫酸ナトリウム、硫酸カリウム、無水硫酸マグネシウム、安息香酸ナトリウム、スクラロース、タウマチン、グリシン、ＤＬ−リンゴ酸およびクエン酸水和物を精製水に溶解し、アセスルファムカリウムおよび／またはサッカリンナトリウムを加え、精製水で溶液の液量を調整し、以下の表１２、表１３および表１４に示す比率の液剤（溶液）を調製した。 Formulation Example 6
Anhydrous sodium sulfate, potassium sulfate, anhydrous magnesium sulfate, sodium benzoate, sucralose, taumatin, glycine, DL-apple acid and citrate hydrate are dissolved in purified water, acesulfam potassium and / or sodium saccharin is added, and in purified water. The amount of the solution was adjusted, and the solutions (solutions) having the ratios shown in Tables 12, 13 and 14 below were prepared.
製剤例７
無水硫酸ナトリウム、硫酸カリウム、無水硫酸マグネシウム、安息香酸ナトリウム、スクラロース、タウマチン、グリシン、ＤＬ−リンゴ酸およびクエン酸水和物を精製水に溶解し、レモン香料（小川香料。ＩＬ７３６０５）を加え、アセスルファムカリウムおよび／またはサッカリンナトリウムを加え、精製水で溶液の液量を調整し、以下の表１５に示す比率の液剤（溶液）を調製した。 Formulation Example 7
Anhydrous sodium sulfate, potassium sulfate, anhydrous magnesium sulfate, sodium benzoate, sucralose, taumatin, glycine, DL-apple acid and citric acid hydrate are dissolved in purified water, lemon fragrance (Ogawa fragrance, IL73605) is added, and assesulfam. Potassium and / or sodium saccharin was added, and the volume of the solution was adjusted with purified water to prepare a solution (solution) having the ratio shown in Table 15 below.
製剤例８
無水硫酸ナトリウム、硫酸カリウム、無水硫酸マグネシウム、安息香酸ナトリウム、スクラロース、タウマチン、グリシン、ＤＬ−リンゴ酸、クエン酸水和物およびサッカリンナトリウムを精製水に溶解し、グレープフルーツ香料（小川香料。ＩＬ６５６１１、ＩＬ６５６１２、ＩＬ６５６１３またはＩＬ６５６１４）を加え、精製水で溶液の液量を調整し、以下の表１６に示す比率の液剤（溶液）を調製した。 Formulation Example 8
Anhydrous sodium sulfate, potassium sulfate, anhydrous magnesium sulfate, sodium benzoate, sucralose, taumatin, glycine, DL-apple acid, citric acid hydrate and sodium saccharin are dissolved in purified water and grapefruit fragrance (Ogawa fragrance. IL65611, IL65612, IL65613 or IL65614) was added, and the amount of the solution was adjusted with purified water to prepare a solution (solution) having the ratio shown in Table 16 below.
製剤例９
グレープフルーツ香料としてＩＬ６５６１１（小川香料）を用いて、製剤例８と同様にして、以下の表１７に示す比率の液剤（溶液）を調製した。 Formulation Example 9
Using IL65611 (Ogawa perfume) as the grapefruit flavor, a liquid preparation (solution) having the ratio shown in Table 17 below was prepared in the same manner as in Preparation Example 8.
製剤例１０
グレープフルーツ香料としてＩＬ６５６１１（小川香料）を用いて、製剤例８と同様にして、以下の表１８に示す比率の液剤（溶液）を調製した。 Formulation Example 10
Using IL65611 (Ogawa flavor) as the grapefruit flavor, a liquid preparation (solution) having the ratio shown in Table 18 below was prepared in the same manner as in Preparation Example 8.
製剤例１１
レモン香料としてＩＬ７３６０４（小川香料）を用いて、製剤例８と同様にして、以下の表１９に示す比率の液剤（溶液）を調製した。 Formulation Example 11
Using IL73604 (Ogawa fragrance) as the lemon fragrance, a liquid preparation (solution) having the ratio shown in Table 19 below was prepared in the same manner as in Preparation Example 8.
製剤例１２
レモン香料としてＩＬ７３６０４（小川香料）を用いて、製剤例８と同様にして、以下の表２０に示す比率の液剤（溶液）を調製した。 Formulation Example 12
Using IL73604 (Ogawa fragrance) as the lemon fragrance, a liquid preparation (solution) having the ratio shown in Table 20 below was prepared in the same manner as in Preparation Example 8.
製剤例１３
ライム香料としてＩＬ７３６０８（小川香料）を用いて、製剤例８と同様にして、以下の表２１に示す比率の液剤（溶液）を調製した。 Preparation Example 13
Using IL73608 (Ogawa fragrance) as the lime fragrance, a liquid preparation (solution) having the ratio shown in Table 21 below was prepared in the same manner as in Preparation Example 8.
製剤例１４
ライム香料としてＩＬ７３６０８（小川香料）を用いて、製剤例８と同様にして、以下の表２２に示す比率の液剤（溶液）を調製した。 Formulation Example 14
Using IL73608 (Ogawa fragrance) as the lime fragrance, a liquid preparation (solution) having the ratio shown in Table 22 below was prepared in the same manner as in Preparation Example 8.
製剤例１５
ライチ香料としてＩＬ６５６１５（小川香料）を用いて、製剤例８と同様にして、以下の表２３に示す比率の液剤（溶液）を調製した。 Formulation Example 15
Using IL65615 (Ogawa fragrance) as the lychee fragrance, a liquid preparation (solution) having the ratio shown in Table 23 below was prepared in the same manner as in Preparation Example 8.
製剤例１６
ライチ香料としてＩＬ６５６１５（小川香料）を用いて、製剤例８と同様にして、以下の表２４に示す比率の液剤（溶液）を調製した。 Formulation Example 16
Using IL65615 (Ogawa fragrance) as the lychee fragrance, a liquid preparation (solution) having the ratio shown in Table 24 below was prepared in the same manner as in Preparation Example 8.
製剤例１７
ライチ香料としてＩＬ６５６１５（小川香料）を用いて、製剤例８と同様にして、以下の表２５に示す比率の液剤（溶液）を調製した。 Preparation Example 17
Using IL65615 (Ogawa fragrance) as the lychee fragrance, a liquid preparation (solution) having the ratio shown in Table 25 below was prepared in the same manner as in Preparation Example 8.
製剤例１８
ライチ香料としてＩＬ６５６１５（小川香料）を用いて、製剤例８と同様にして、以下の表２６に示す比率の液剤（溶液）を調製した。 Formulation Example 18
Using IL65615 (Ogawa fragrance) as the lychee fragrance, a liquid preparation (solution) having the ratio shown in Table 26 below was prepared in the same manner as in Preparation Example 8.
製剤例１９
ライチ香料としてＩＬ６５６１５（小川香料）を用いて、製剤例８と同様にして、以下の表２７に示す比率の液剤（溶液）を調製した。 Formulation Example 19
Using IL65615 (Ogawa fragrance) as the lychee fragrance, a liquid preparation (solution) having the ratio shown in Table 27 below was prepared in the same manner as in Preparation Example 8.
製剤例２０
以下の表２８に示す比率の製剤（１ボトル当たり）を調製する。
無水硫酸ナトリウム、硫酸カリウムおよび硫酸マグネシウム７水和物を精製水に添加し攪拌して得られた溶解液に、安息香酸ナトリウム、クエン酸水和物、ＤＬ−リンゴ酸、スクラロース、グリシンおよびサッカリンナトリウムを添加して攪拌する。得られた溶解液を約６５℃で１０分間加温した後、４０℃以下に冷却する。精製水に溶解して除菌ろ過したタウマチン及び除菌ろ過したレモン香料（小川香料。ＩＬ７３６０４）を、冷却した上記の溶解液に加え、精製水を加えて液量を調整する。不溶物を除去するため、得られた調製液をろ過し、ろ液（製剤）を分注して５００ｍｌ容ポリエチレンテレフタラート製ボトルに充填し、ポリエチレン製キャップで施栓する。 Formulation example 20
Prepare the formulations (per bottle) in the ratios shown in Table 28 below.
Sodium benzoate, citric acid hydrate, DL-malic acid, sucralose, glycine and sodium saccharin were added to the solution obtained by adding anhydrous sodium sulfate, potassium sulfate and magnesium sulfate heptahydrate to purified water and stirring. Add and stir. The obtained solution is heated at about 65 ° C. for 10 minutes and then cooled to 40 ° C. or lower. Taumatin dissolved in purified water and sterilized and filtered and lemon fragrance sterilized and filtered (Ogawa fragrance. IL73604) are added to the above-cooled solution, and purified water is added to adjust the amount of the solution. In order to remove the insoluble matter, the obtained preparation solution is filtered, the filtrate (formulation) is dispensed, filled in a 500 ml polyethylene terephthalate bottle, and capped with a polyethylene cap.
試験例１
タウマチン（甘味料）の濃度の影響を調べるため、製剤例１で得た製剤１−１、１−２、１−３および１−４の溶液をそれぞれ少量ずつ口に含んで味見をし、試験者１名により官能試験を行った。評価は甘味を感じないとき０、わずかに甘味を感じたとき１、甘味があると感じたとき２と評価した。また塩味及び苦みについて、タウマチンが０ｍｇ配合されている製剤（製剤１−５）と比較して、明らかに抑制が感じられる場合０、わずかに抑制が感じられる場合１、同等である（効果なし）場合２、増強されている場合３と評価した。結果を表２９に示す。タウマチンの濃度が高くなるにつれて、塩味自体は抑えられていると感じられ、また、他の不快な味（苦味）が抑制されたためかもしれないが、塩味がシャープになったと感じた。 Test Example 1
In order to investigate the effect of the concentration of taumatin (sweetener), the solutions of preparations 1-1, 1-2, 1-3 and 1-4 obtained in preparation example 1 were put into the mouth in small amounts and tasted for testing. A sensory test was performed by one person. The evaluation was 0 when no sweetness was felt, 1 when a slight sweetness was felt, and 2 when a slight sweetness was felt. In addition, the saltiness and bitterness are equivalent to 0 when a clear suppression is felt and 1 when a slight suppression is felt, as compared with the preparation containing 0 mg of taumatin (formulation 1-5) (no effect). Case 2 and enhanced case 3 were evaluated. The results are shown in Table 29. As the concentration of taumatin increased, the salty taste itself was felt to be suppressed, and the salty taste became sharper, which may be due to the suppression of other unpleasant tastes (bitterness).
試験例２
サッカリンナトリウム（甘味料）の濃度の影響を調べるため、製剤例３（３）で得た製剤３（３）−１、３（３）−２および３（３）−３溶液をそれぞれ少量ずつ口に含んで味見をし、試験者４名（Ａ〜Ｄ）により官能試験を行った。評価は甘味について味のよい製剤に○をつけた。結果を表３０に示す。 Test Example 2
In order to investigate the effect of the concentration of sodium saccharin (sweetener), a small amount of each of the solutions 3 (3) -1, 3 (3) -2 and 3 (3) -3 obtained in Preparation Example 3 (3) was put into the mouth. The taste was included, and a sensory test was conducted by four testers (A to D). For the evaluation, the sweetness was marked with a circle. The results are shown in Table 30.
試験例３
クエン酸水和物（矯味料）の濃度の影響を調べるため、製剤例９で得た製剤９−１、９−２、９−３および９−４の溶液をそれぞれ約４０ｍｌずつ口に含んで味見をし、試験者５名（Ａ〜Ｅ）により官能試験を行った。評価は、飲めそうだと感じた液には○をつけて、受容性得点として１点とした。また、味が良いと感じた順番で順位をつけ、一位を４点、二位を３点、三位を２点、四位を１点として順位得点をつけた。結果を表３１に示す。 Test Example 3
In order to investigate the effect of the concentration of citric acid hydrate (flavoring agent), about 40 ml of each of the solutions of the preparations 9-1, 9-2, 9-3 and 9-4 obtained in the preparation example 9 was contained in the mouth. After tasting, a sensory test was conducted by 5 testers (A to E). The evaluation was given as a receptive score of 1 by marking the liquids that seemed to be drinkable. In addition, the rankings were given in the order in which they felt the taste was good, with the first place being 4 points, the second place being 3 points, the third place being 2 points, and the fourth place being 1 point. The results are shown in Table 31.
試験例４
サッカリンナトリウム（甘味料）の濃度の影響を調べるため、製剤例１０で得た製剤１０−２、１０−３、１０−４および１０−５の溶液をそれぞれ約４０ｍｌずつ口に含んで味見をし、試験者６名（Ａ〜Ｆ）により官能試験を行った。評価は、飲めそうだと感じた液には○をつけて、受容性得点として１点とした。また、味が良いと感じた順番で順位をつけ、一位を４点、二位を３点、三位を２点、四位を１点として順位得点をつけた。結果を表３２に示す。 Test Example 4
In order to investigate the effect of the concentration of sodium saccharin (sweetener), about 40 ml of each of the solutions of the preparations 10-2, 10-3, 10-4 and 10-5 obtained in the preparation example 10 was put in the mouth and tasted. A sensory test was performed by 6 testers (A to F). The evaluation was given as a receptive score of 1 by marking the liquids that seemed to be drinkable. In addition, the rankings were given in the order in which they felt the taste was good, with the first place being 4 points, the second place being 3 points, the third place being 2 points, and the fourth place being 1 point. The results are shown in Table 32.
次に、タウマチン（甘味料）の濃度の影響を調べるため、製剤例１０で得た製剤１０−１および１０−２の溶液それぞれ約２５０ｍｌを数回に分けて口に含み味見をし、味が良いと感じた順番で順位をつけ、一位を２点、二位を１点として順位得点をつけた。結果を表３３に示す。 Next, in order to investigate the effect of the concentration of taumatin (sweetener), about 250 ml of each of the solutions of the preparations 10-1 and 10-2 obtained in the preparation example 10 was contained in the mouth in several times and tasted. The rankings were given in the order in which they felt good, with 2 points for the 1st place and 1 point for the 2nd place. The results are shown in Table 33.
試験例５
クエン酸水和物（矯味料）の濃度の影響を調べるため、製剤例１１で得た製剤１１−１、１１−２、１１−３および１１−４の溶液をそれぞれ約４０ｍｌずつ口に含んで味見をし、試験者５名（Ａ〜Ｅ）により官能試験を行った。評価は、飲めそうだと感じた液には○をつけて、受容性得点として１点とした。また、味が良いと感じた順番で順位をつけ、一位を４点、二位を３点、三位を２点、四位を１点として順位得点をつけた。結果を表３４に示す。 Test Example 5
In order to investigate the effect of the concentration of citric acid hydrate (flavoring agent), about 40 ml of each of the solutions of the preparations 11-1, 11-2, 11-3 and 11-4 obtained in the preparation example 11 was contained in the mouth. After tasting, a sensory test was conducted by 5 testers (A to E). The evaluation was given as a receptive score of 1 by marking the liquids that seemed to be drinkable. In addition, the rankings were given in the order in which they felt the taste was good, with the first place being 4 points, the second place being 3 points, the third place being 2 points, and the fourth place being 1 point. The results are shown in Table 34.
試験例６
サッカリンナトリウム（甘味料）の濃度の影響を調べるため、製剤例１２で得た製剤１２−２、１２−３、１２−４および１２−５の溶液をそれぞれ約４０ｍｌずつ口に含んで味見をし、試験者６名（Ａ〜Ｆ）により官能試験を行った。評価は、飲めそうだと感じた液には○をつけて、受容性得点として１点とした。また、味が良いと感じた順番で順位をつけ、一位を４点、二位を３点、三位を２点、四位を１点として順位得点をつけた。結果を表３５に示す。 Test Example 6
In order to investigate the effect of the concentration of sodium saccharin (sweetener), about 40 ml of each of the solutions of the preparations 12-2, 12-3, 12-4 and 12-5 obtained in the preparation example 12 was put in the mouth and tasted. A sensory test was performed by 6 testers (A to F). The evaluation was given as a receptive score of 1 by marking the liquids that seemed to be drinkable. In addition, the rankings were given in the order in which they felt the taste was good, with the first place being 4 points, the second place being 3 points, the third place being 2 points, and the fourth place being 1 point. The results are shown in Table 35.
次に、タウマチン（甘味料）の濃度の影響を調べるため、製剤１２−１および１２−４の液それぞれ約２５０ｍｌを数回に分けて口に含み味見をし、味が良いと感じた順番で順位をつけ、一位を２点、二位を１点として順位得点をつけた。結果を表３６に示す。 Next, in order to investigate the effect of the concentration of taumatin (sweetener), about 250 ml of each of the solutions 12-1 and 12-4 was put in the mouth in several times and tasted, and in the order in which the taste was felt good. The ranking was given, with 2 points for the 1st place and 1 point for the 2nd place. The results are shown in Table 36.
試験例７
クエン酸水和物（矯味料）の濃度の影響を調べるため、製剤例１３で得た製剤１３−１、１３−２、１３−３および１３−４の溶液をそれぞれ約４０ｍｌずつ口に含んで味見をし、試験者５名（Ａ〜Ｅ）により官能試験を行った。評価は、飲めそうだと感じた液には○をつけて、受容性得点として１点とした。また、味が良いと感じた順番で順位をつけ、一位を４点、二位を３点、三位を２点、四位を１点として順位得点をつけた。結果を表３７に示す。 Test Example 7
In order to investigate the effect of the concentration of citric acid hydrate (flavoring agent), about 40 ml of each of the solutions of the preparations 13-1, 13-2, 13-3 and 13-4 obtained in the preparation example 13 was contained in the mouth. After tasting, a sensory test was conducted by 5 testers (A to E). The evaluation was given as a receptive score of 1 by marking the liquids that seemed to be drinkable. In addition, the rankings were given in the order in which they felt the taste was good, with the first place being 4 points, the second place being 3 points, the third place being 2 points, and the fourth place being 1 point. The results are shown in Table 37.
試験例８
サッカリンナトリウム（甘味料）の濃度の影響を調べるため、製剤例１４で得た製剤１４−２、１４−３、１４−４および１４−５の溶液をそれぞれ約４０ｍｌずつ口に含んで味見をし、試験者６名（Ａ〜Ｆ）により官能試験を行った。評価は、飲めそうだと感じた液には○をつけて、受容性得点として１点とした。また、味が良いと感じた順番で順位をつけ、一位を４点、二位を３点、三位を２点、四位を１点として順位得点をつけた。結果を表３８に示す。 Test Example 8
In order to investigate the effect of the concentration of sodium saccharin (sweetener), about 40 ml of each of the solutions of the preparations 14-2, 14-3, 14-4 and 14-5 obtained in the preparation example 14 was put in the mouth and tasted. A sensory test was performed by 6 testers (A to F). The evaluation was given as a receptive score of 1 by marking the liquids that seemed to be drinkable. In addition, the rankings were given in the order in which they felt the taste was good, with the first place being 4 points, the second place being 3 points, the third place being 2 points, and the fourth place being 1 point. The results are shown in Table 38.
次に、タウマチン（甘味料）の濃度の影響を調べるため、製剤１４−１および１４−３の溶液それぞれ約２５０ｍｌを数回に分けて口に含み味見をし、味が良いと感じた順番で順位をつけ、一位を２点、二位を１点として順位得点をつけた。結果を表３９に示す。 Next, in order to investigate the effect of the concentration of taumatin (sweetener), about 250 ml of each of the solutions 14-1 and 14-3 was put in the mouth in several times and tasted, and in the order in which the taste was felt good. The ranking was given, with 2 points for the 1st place and 1 point for the 2nd place. The results are shown in Table 39.
試験例９
クエン酸水和物（矯味料）の濃度の影響を調べるため、製剤例１５で得た製剤１５−１、１５−２および１５−３の溶液をそれぞれ約４０ｍｌずつ口に含んで味見をし、試験者５名（Ａ〜Ｅ）により官能試験を行った。評価は、飲めそうだと感じた液には○をつけて、受容性得点として１点とした。また、味が良いと感じた順番で順位をつけ、一位を３点、二位を２点、三位を１点として順位得点をつけた。結果を表４０に示す。 Test Example 9
In order to investigate the effect of the concentration of citric acid hydrate (flavoring agent), about 40 ml of each of the solutions of the preparations 15-1, 15-2 and 15-3 obtained in the preparation example 15 was contained in the mouth and tasted. A sensory test was performed by 5 testers (A to E). The evaluation was given as a receptive score of 1 by marking the liquids that seemed to be drinkable. In addition, the rankings were given in the order in which they felt the taste was good, with the first place being 3 points, the second place being 2 points, and the third place being 1 point. The results are shown in Table 40.
試験例１０
サッカリンナトリウム（甘味料）の濃度の影響を調べるため、製剤例１９で得た製剤１９−２、１９−３、１９−４および１９−５の溶液をそれぞれ約４０ｍｌずつ口に含んで味見をし、試験者６名（Ａ〜Ｆ）により官能試験を行った。評価は、飲めそうだと感じた液には○をつけて、受容性得点として１点とした。また、味が良いと感じた順番で順位をつけ、一位を４点、二位を３点、三位を２点、四位を１点として順位得点をつけた。結果を表４１に示す。 Test Example 10
In order to investigate the effect of the concentration of sodium saccharin (sweetener), about 40 ml of each of the solutions of the preparations 19-2, 19-3, 19-4 and 19-5 obtained in the preparation example 19 was put in the mouth and tasted. A sensory test was performed by 6 testers (A to F). The evaluation was given as a receptive score of 1 by marking the liquids that seemed to be drinkable. In addition, the rankings were given in the order in which they felt the taste was good, with the first place being 4 points, the second place being 3 points, the third place being 2 points, and the fourth place being 1 point. The results are shown in Table 41.
次に、タウマチン（甘味料）の濃度の影響を調べるため、製剤１９−１および１９−４の溶液それぞれ約２５０ｍｌを数回に分けて口に含み味見をし、評価は味が良いと感じた順番で順位をつけ、一位を２点、二位を１点として順位得点をつけた。結果を表４２に示す。 Next, in order to investigate the effect of the concentration of taumatin (sweetener), about 250 ml of each of the solutions of preparations 19-1 and 19-4 was put in the mouth in several times and tasted, and the evaluation felt that the taste was good. The rankings were given in order, with 2 points for the 1st place and 1 point for the 2nd place. The results are shown in Table 42.
以上の官能試験の結果から、本発明の要件を満たす医薬組成物は、塩味や苦味をほとんど感じさせず、容易に服用することができることが明らかである。 From the results of the above sensory test, it is clear that the pharmaceutical composition satisfying the requirements of the present invention can be easily taken with almost no salty taste or bitterness.
本発明の医薬組成物は、腸管内容物の排除のための高い洗浄効果を有しながら、塩味や苦味をほとんど感じずに容易に服用することができるため、腸管内容物を洗浄流去するために、大腸内視鏡検査の前処理、バリウム注腸Ｘ線検査の前処理または大腸手術の前処理として経口投与することができる。従って、本発明の医薬組成物は、極めて有用である。 Since the pharmaceutical composition of the present invention has a high cleaning effect for eliminating the intestinal contents and can be easily taken with almost no salty taste or bitterness, the intestinal contents are washed away. It can be orally administered as a pretreatment for colonoscopy, a pretreatment for barium enema X-ray examination, or a pretreatment for colorectal surgery. Therefore, the pharmaceutical composition of the present invention is extremely useful.
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