WO2011148794A1 - Dimemorfan-containing liquid preparation for internal administration - Google Patents
Dimemorfan-containing liquid preparation for internal administration Download PDFInfo
- Publication number
- WO2011148794A1 WO2011148794A1 PCT/JP2011/061024 JP2011061024W WO2011148794A1 WO 2011148794 A1 WO2011148794 A1 WO 2011148794A1 JP 2011061024 W JP2011061024 W JP 2011061024W WO 2011148794 A1 WO2011148794 A1 WO 2011148794A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- dimemorphan
- bitterness
- sucralose
- beverage
- throat
- Prior art date
Links
- 229960001056 dimemorfan Drugs 0.000 title claims abstract description 35
- KBEZZLAAKIIPFK-NJAFHUGGSA-N dimemorfan Chemical compound C1C2=CC=C(C)C=C2[C@@]23CCN(C)[C@@H]1[C@H]2CCCC3 KBEZZLAAKIIPFK-NJAFHUGGSA-N 0.000 title claims abstract description 34
- 239000007788 liquid Substances 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title abstract description 10
- 235000013361 beverage Nutrition 0.000 claims abstract description 28
- 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 abstract description 23
- 239000004376 Sucralose Substances 0.000 claims abstract description 20
- 235000019408 sucralose Nutrition 0.000 claims abstract description 20
- 150000005846 sugar alcohols Chemical class 0.000 claims abstract description 19
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims abstract description 10
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims abstract description 10
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 12
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 12
- 239000000811 xylitol Substances 0.000 claims description 12
- 235000010447 xylitol Nutrition 0.000 claims description 12
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 12
- 229960002675 xylitol Drugs 0.000 claims description 12
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 7
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 7
- 239000000600 sorbitol Substances 0.000 claims description 7
- 235000010356 sorbitol Nutrition 0.000 claims description 7
- 229960002920 sorbitol Drugs 0.000 claims description 7
- 239000004386 Erythritol Substances 0.000 claims description 6
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 claims description 6
- 235000019414 erythritol Nutrition 0.000 claims description 6
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 claims description 6
- 229940009714 erythritol Drugs 0.000 claims description 6
- 239000000845 maltitol Substances 0.000 claims description 6
- 235000010449 maltitol Nutrition 0.000 claims description 6
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 claims description 6
- 229940035436 maltitol Drugs 0.000 claims description 6
- 235000019658 bitter taste Nutrition 0.000 abstract description 25
- 239000008213 purified water Substances 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 229910019142 PO4 Inorganic materials 0.000 description 14
- 239000010452 phosphate Substances 0.000 description 14
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 14
- 230000007794 irritation Effects 0.000 description 10
- 241000544066 Stevia Species 0.000 description 8
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 8
- 206010043521 Throat irritation Diseases 0.000 description 7
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 5
- 229940100688 oral solution Drugs 0.000 description 5
- 229940124584 antitussives Drugs 0.000 description 4
- 229960001948 caffeine Drugs 0.000 description 4
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 3
- 230000000954 anitussive effect Effects 0.000 description 3
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 206010011224 Cough Diseases 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000003434 antitussive agent Substances 0.000 description 2
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 235000019640 taste Nutrition 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- AKNNEGZIBPJZJG-MSOLQXFVSA-N (-)-noscapine Chemical compound CN1CCC2=CC=3OCOC=3C(OC)=C2[C@@H]1[C@@H]1C2=CC=C(OC)C(OC)=C2C(=O)O1 AKNNEGZIBPJZJG-MSOLQXFVSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 206010049590 Upper respiratory tract inflammation Diseases 0.000 description 1
- AKNNEGZIBPJZJG-UHFFFAOYSA-N alpha-noscapine Natural products CN1CCC2=CC=3OCOC=3C(OC)=C2C1C1C2=CC=C(OC)C(OC)=C2C(=O)O1 AKNNEGZIBPJZJG-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- OJGDCBLYJGHCIH-UHFFFAOYSA-N bromhexine Chemical compound C1CCCCC1N(C)CC1=CC(Br)=CC(Br)=C1N OJGDCBLYJGHCIH-UHFFFAOYSA-N 0.000 description 1
- 229960003870 bromhexine Drugs 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 229960000456 carbinoxamine maleate Drugs 0.000 description 1
- GVNWHCVWDRNXAZ-BTJKTKAUSA-N carbinoxamine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(OCCN(C)C)C1=CC=C(Cl)C=C1 GVNWHCVWDRNXAZ-BTJKTKAUSA-N 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229960000920 dihydrocodeine Drugs 0.000 description 1
- RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 description 1
- -1 dimemorphan salt Chemical class 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 239000012676 herbal extract Substances 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 239000008123 high-intensity sweetener Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- INAXVFBXDYWQFN-XHSDSOJGSA-N morphinan Chemical group C1C2=CC=CC=C2[C@]23CCCC[C@H]3[C@@H]1NCC2 INAXVFBXDYWQFN-XHSDSOJGSA-N 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 239000004081 narcotic agent Substances 0.000 description 1
- PLPRGLOFPNJOTN-UHFFFAOYSA-N narcotine Natural products COc1ccc2C(OC(=O)c2c1OC)C3Cc4c(CN3C)cc5OCOc5c4OC PLPRGLOFPNJOTN-UHFFFAOYSA-N 0.000 description 1
- 235000013615 non-nutritive sweetener Nutrition 0.000 description 1
- 239000000820 nonprescription drug Substances 0.000 description 1
- 229960004708 noscapine Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
- A23L27/30—Artificial sweetening agents
- A23L27/33—Artificial sweetening agents containing sugars or derivatives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
- A23L27/30—Artificial sweetening agents
- A23L27/33—Artificial sweetening agents containing sugars or derivatives
- A23L27/34—Sugar alcohols
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
- A23L27/30—Artificial sweetening agents
- A23L27/33—Artificial sweetening agents containing sugars or derivatives
- A23L27/37—Halogenated sugars
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
- A23L27/86—Addition of bitterness inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive agents
Definitions
- the present invention relates to an internal use liquid preparation or beverage containing dimemorphan.
- Dimemorphan is an antitussive agent having a morphinan skeleton and has a strong antitussive effect. It is a non-narcotic drug with no central dependence, and is used for upper respiratory tract inflammation, acute bronchitis, and pneumonia. It is also used as a cough syrup for over-the-counter medicines.
- Beverages such as internal preparations are easier to swallow than solid preparations, and have the advantage of being easy to take for people with low swallowing function such as children and the elderly and people with symptoms such as cough.
- the taste of dimemorphan is bitter, and when it is used as a beverage, the ingestibility is poor from the aspect of flavor. Therefore, it is necessary to reduce the bitterness by using a sweetener such as sugar alcohol and to design it to be easy to drink.
- An object of the present invention is to reduce bitterness and throat irritation peculiar to dimemorphan and / or a salt thereof in an oral solution or beverage.
- dimemorphan and / or its salt-containing oral solution or beverage can be combined with sugar alcohol and / or trehalose and sucralose together so that it is unique to dimemorphan.
- sugar alcohol and / or trehalose and sucralose can be combined with sugar alcohol and / or trehalose and sucralose together so that it is unique to dimemorphan.
- the bitter taste of the throat can be improved and also the irritation to the throat can be reduced, and the present invention has been completed.
- the present invention provides (1) a) dimemorphan and / or a salt thereof, b) a sugar alcohol and / or trehalose, c) an internal liquid or beverage containing sucralose, (2) The internal liquid or beverage according to (1) above, wherein b) component is 180 parts by mass or more and c) component is 0.1 parts by mass or more with respect to 1 part by mass of a) component a) (3) The internal liquid or beverage according to (1) or (2), wherein the sugar alcohol is at least one selected from the group consisting of xylitol, sorbitol, erythritol and maltitol, It is.
- Examples of the “dimemorphan salt” of the present invention include salts acceptable as an oral solution or beverage, such as hydrochloride, sulfate, nitrate, phosphate, maleate, and fumarate. Merolphan phosphate.
- sucrose alcohol in the present invention, erythritol, xylitol, maltitol, inositol, sorbitol, mannitol, maltitol and the like can be used, and xylitol and sorbitol are preferable.
- the amount of sugar alcohol and / or trehalose in the present invention (the total amount in the case of 2 or more types) is usually 180 parts by mass or more, preferably 1 part by mass of dimemorphan Is 184 parts by mass or more, more preferably 230 parts by mass or more, and most preferably 260 parts by mass or more.
- the blending amount of sucralose at this time is preferably 0.1 parts by mass or more per 1 part by mass of dimemorphan and / or a salt thereof (in the case of blending two or more).
- the “internal liquid” in the present invention is not particularly limited as long as it is a liquid that can be taken internally. Examples thereof include pharmaceuticals such as internal liquids and drinks and quasi drugs. In addition, “beverages” include various beverages in the food area such as nutritionally functional foods and foods for specified insurance.
- vitamins, minerals, amino acids, herbal medicines, herbal extracts, caffeine, etc. can be appropriately blended within a range not impairing the effects of the present invention.
- additives such as antioxidants, coloring agents, flavoring agents, flavoring agents, surfactants, solubilizers, preservatives, sugar alcohols, sweeteners other than trehalose, and high-intensity sweeteners other than sucralose as necessary Can be appropriately blended within a range not impairing the effects of the present invention.
- additives and the like may be blended singly or in combination of two or more.
- the method for preparing the internal liquid or beverage of the present invention is not particularly limited. Usually, dimemorphan and / or its salt, sugar alcohol and / or trehalose, sucralose, and other ingredients as necessary are dissolved in a suitable amount of purified water, and then the volume is adjusted by adding further purified water. Accordingly, by performing filtration and sterilization treatment, it can be provided as a dimemorphan-containing internal solution or beverage.
- Test Example (1) Preparation of Each Internal Solution or Beverage Each internal solution or beverage of Reference Example 1-3, Example 1-7 and Comparative Example 1-3 shown below was prepared.
- Reference example 1 Dimemorphan phosphate 60 mg and xylitol 16000 mg were dissolved in purified water to a total volume of 40 mL.
- Reference example 2 Anhydrous caffeine 3.3 mg and xylitol 16000 mg were dissolved in purified water to make a total volume of 40 mL.
- Reference example 3 Dimemorphan phosphate 60 mg and xylitol 18000 mg were dissolved in purified water to a total volume of 40 mL.
- Example 1 Dimemorphan phosphate 60 mg, xylitol 16000 mg and sucralose 6.6 mg were dissolved in purified water to make a total volume of 40 mL.
- Example 2 Dimemorphan phosphate 60 mg, sorbitol 14000 mg and sucralose 6.6 mg were dissolved in purified water to make a total volume of 40 mL.
- Example 3 Dimemorphan phosphate 60 mg, xylitol 16000 mg, stevia 7.4 mg and sucralose 4.4 mg were dissolved in purified water to a total volume of 40 mL.
- Example 4 Dimemorphan phosphate 60 mg, erythritol 8000 mg and sucralose 4.4 mg were dissolved in purified water to make a total volume of 40 mL.
- Example 5 Dimemorphan phosphate 60 mg, maltitol 16000 mg and sucralose 4.4 mg were dissolved in purified water to make a total volume of 40 mL.
- Example 6 Dimemorphan phosphate 60 mg, trehalose 16000 mg and sucralose 4.4 mg were dissolved in purified water to make a total volume of 40 mL.
- Example 7 Dimemorphan phosphate 60 mg, xylitol 4200 mg, sorbitol 10080 mg, trehalose 1500 mg and sucralose 10.6 mg, stevia 17.7 mg were dissolved in purified water to make a total volume of 40 mL.
- Comparative Example 1 Dimemorphan phosphate 60 mg and sucralose 33.3 mg were dissolved in purified water to make a total volume of 40 mL.
- Comparative Example 2 Dimemorphan phosphate 60 mg and stevia 110.8 mg were dissolved in purified water to a total volume of 40 mL.
- Comparative Example 3 Dimemorphan phosphate 60 mg, xylitol 16000 mg and stevia 22 mg were dissolved in purified water to a total volume of 40 mL.
- sweetness (%) Sucrose (sugar) concentration in 100 mL [w / v%] The sweetness level of 1% corresponds to the sweetness level of a 1% sucrose aqueous solution.
- Example 1 From the results of Example 1, it was found that bitterness and irritation to the throat were reduced by simultaneously blending sucralose with an internal solution containing dimethylmorphane and sugar alcohol. From the results of Comparative Example 1, when sucralose is added to dimemorphan and sucralose is added to adjust the sweetness to the same level as in Example 1, although irritation to the throat is reduced, bitterness may not be reduced. all right. Similarly, from the result of Comparative Example 2, it was found that bitterness was not reduced even when stevia was added to dimemorphan to adjust the sweetness to the same level as in Example 1.
- Example 6 From the results of Example 6, it was found that even if trehalose was blended in place of the sugar alcohols blended in Examples 1, 2, 4, and 5, the bitter taste and throat irritation of dimethylmorphane were reduced.
- Example 3 From the results of Example 3, even if stevia is further added to the internal liquid preparation containing dimemorphan, sugar alcohol and sucralose, bitterness and irritation to the throat are similar to those in Example 1 and can be added. all right.
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Abstract
A sugar alcohol and/or trehalose and sucralose are added to a liquid preparation for internal administration or beverage containing dimemorfan and/or a salt thereof. In this manner, it becomes possible to reduce the bitterness inherent in dimemorfan and also reduce stimuli to the throat.
Description
本発明は、ジメモルファンを含有する内服液剤または飲料に関する。
The present invention relates to an internal use liquid preparation or beverage containing dimemorphan.
ジメモルファンは、モルヒナン骨格を有する鎮咳剤で、強力な鎮咳作用を有している。中枢性の依存性がない非麻薬性薬剤であり、上気道炎、急性気管支炎、肺炎に対して用いられており、一般用医薬品の咳止めシロップ剤としても使用されている。
Dimemorphan is an antitussive agent having a morphinan skeleton and has a strong antitussive effect. It is a non-narcotic drug with no central dependence, and is used for upper respiratory tract inflammation, acute bronchitis, and pneumonia. It is also used as a cough syrup for over-the-counter medicines.
内服製剤等の飲料は、固形製剤に比べ飲み込み易く、こどもや老人など嚥下機能が低い人や咳等の症状がある人にとって服用しやすいという利点がある。しかし、ジメモルファンの味は苦く、飲料にした場合、風味の面から服用性が悪くなる。そこで、糖アルコール等の甘味剤の使用により、苦味を低減させ、飲みやすく設計する必要がある。
Beverages such as internal preparations are easier to swallow than solid preparations, and have the advantage of being easy to take for people with low swallowing function such as children and the elderly and people with symptoms such as cough. However, the taste of dimemorphan is bitter, and when it is used as a beverage, the ingestibility is poor from the aspect of flavor. Therefore, it is necessary to reduce the bitterness by using a sweetener such as sugar alcohol and to design it to be easy to drink.
これまでも苦味等を呈する薬物を含有するために、味を改善する方法が開発されてきた。例えば、ステビアの使用により、リン酸ジヒドロコデインやマレイン酸カルビノキサミンなどの苦味を改善した感冒用組成物ができること（特許文献１参照）、エリスリトールの使用により、ノスカピン、ブロムヘキシンの苦味を軽減した経口液剤ができること（特許文献２参照）が報告されている。
So far, methods for improving taste have been developed in order to contain drugs that exhibit bitterness and the like. For example, by using stevia, a composition for colds with improved bitterness such as dihydrocodeine phosphate and carbinoxamine maleate can be produced (see Patent Document 1), and by using erythritol, an oral solution with reduced bitterness of noscapine and bromhexine can be produced. (See Patent Document 2).
また、口腔内で崩壊又は溶解させて服用する鎮咳用固形製剤の中には、苦味だけでなく、服用する際に喉へのいがらっぽさを有する薬物が存在するが、マンニトール等を配合して喉へのいがらっぽさを低減した例が報告されている（特許文献３参照）。
In addition, some antitussive solid preparations that are disintegrated or dissolved in the oral cavity take drugs that have not only bitterness but also throat irritation when taken, but contain mannitol, etc. And the example which reduced the irritability to a throat has been reported (refer patent document 3).
しかし、鎮咳剤を含む内服液剤については、公知の方法によって苦味の改善がなされているものの、喉への刺激を低減するという課題は未だ解決されていない。そこで、苦味と喉への刺激との両方を低減させた鎮咳剤含有内服液剤または飲料が求められていた。
However, with respect to internal liquid preparations including antitussive agents, although the bitterness has been improved by a known method, the problem of reducing irritation to the throat has not yet been solved. Therefore, an antitussive-containing internal solution or beverage that reduces both bitterness and throat irritation has been demanded.
本発明者らは、ジメモルファン及び／又はその塩を含有する内服液剤または飲料に糖アルコールを高濃度配合しても、苦味が低減されず、また喉への刺激も低減されないことを確認した。本発明は、内服液剤または飲料中のジメモルファン及び／又はその塩特有の苦味及び喉への刺激を低減することを課題とする。
The inventors of the present invention have confirmed that bitterness is not reduced and irritation to the throat is not reduced even when a high concentration of sugar alcohol is added to an internal solution or beverage containing dimethylmorphane and / or a salt thereof. An object of the present invention is to reduce bitterness and throat irritation peculiar to dimemorphan and / or a salt thereof in an oral solution or beverage.
本発明者らは、上記課題を解決すべく鋭意研究を重ねた結果、ジメモルファン及び／又はその塩含有内服液剤または飲料に糖アルコール及び／又はトレハロース、並びにスクラロースを一緒に配合することにより、ジメモルファン特有の苦味を改善し、さらには喉への刺激も低減することができることを突き止め、本発明を完成するに至った。
As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that dimemorphan and / or its salt-containing oral solution or beverage can be combined with sugar alcohol and / or trehalose and sucralose together so that it is unique to dimemorphan. As a result, it was found that the bitter taste of the throat can be improved and also the irritation to the throat can be reduced, and the present invention has been completed.
すなわち、本発明は
（１）ａ）ジメモルファン及び／又はその塩、ｂ）糖アルコール及び／又はトレハロース、ｃ）スクラロースを含有する内服液剤または飲料、
（２）ａ）成分１質量部に対して、ｂ）成分が１８０質量部以上であり、かつｃ）成分が０．１質量部以上である前記（１）に記載の内服液剤または飲料、
（３）糖アルコールが、キシリトール、ソルビトール、エリスリトール及びマルチトールからなる群より選択される少なくとも１種である、前記（１）又は（２）に記載の内服液剤または飲料、
である。 That is, the present invention provides (1) a) dimemorphan and / or a salt thereof, b) a sugar alcohol and / or trehalose, c) an internal liquid or beverage containing sucralose,
(2) The internal liquid or beverage according to (1) above, wherein b) component is 180 parts by mass or more and c) component is 0.1 parts by mass or more with respect to 1 part by mass of a) component a)
(3) The internal liquid or beverage according to (1) or (2), wherein the sugar alcohol is at least one selected from the group consisting of xylitol, sorbitol, erythritol and maltitol,
It is.
（１）ａ）ジメモルファン及び／又はその塩、ｂ）糖アルコール及び／又はトレハロース、ｃ）スクラロースを含有する内服液剤または飲料、
（２）ａ）成分１質量部に対して、ｂ）成分が１８０質量部以上であり、かつｃ）成分が０．１質量部以上である前記（１）に記載の内服液剤または飲料、
（３）糖アルコールが、キシリトール、ソルビトール、エリスリトール及びマルチトールからなる群より選択される少なくとも１種である、前記（１）又は（２）に記載の内服液剤または飲料、
である。 That is, the present invention provides (1) a) dimemorphan and / or a salt thereof, b) a sugar alcohol and / or trehalose, c) an internal liquid or beverage containing sucralose,
(2) The internal liquid or beverage according to (1) above, wherein b) component is 180 parts by mass or more and c) component is 0.1 parts by mass or more with respect to 1 part by mass of a) component a)
(3) The internal liquid or beverage according to (1) or (2), wherein the sugar alcohol is at least one selected from the group consisting of xylitol, sorbitol, erythritol and maltitol,
It is.
本発明により、ジメモルファン及び／又はその塩を含有する内服液剤又は飲料の苦味及び喉への刺激を低減することができた。
According to the present invention, it was possible to reduce the bitterness and throat irritation of an internal solution or beverage containing dimemorphan and / or a salt thereof.
本発明の「ジメモルファンの塩」としては、塩酸塩、硫酸塩、硝酸塩、リン酸塩、マレイン酸塩、フマル酸塩など内服液剤又は飲料として許容可能な塩が挙げられるが、最も好ましいのはジメモルファンリン酸塩である。
Examples of the “dimemorphan salt” of the present invention include salts acceptable as an oral solution or beverage, such as hydrochloride, sulfate, nitrate, phosphate, maleate, and fumarate. Merolphan phosphate.
本発明における「糖アルコール」には、エリスリトール、キシリトール、マルチトール、イノシトール、ソルビトール、マンニトール、マルチトール等を使用することができるが、好ましいのはキシリトール、ソルビトールである。
As the “sugar alcohol” in the present invention, erythritol, xylitol, maltitol, inositol, sorbitol, mannitol, maltitol and the like can be used, and xylitol and sorbitol are preferable.
本発明の効果を十分に奏するために、本発明における糖アルコール及び／またはトレハロースの配合量（２種以上配合の場合は合計量）は、ジメモルファン１質量部に対して通常１８０質量部以上、好ましくは１８４質量部以上、より好ましくは２３０質量部以上、最も好ましくは２６０質量部以上である。このときのスクラロースの配合量は、ジメモルファン及び／又はその塩（２種以上配合の場合は合計量）１質量部に対して０．１質量部以上であることが好ましい。
In order to sufficiently exhibit the effects of the present invention, the amount of sugar alcohol and / or trehalose in the present invention (the total amount in the case of 2 or more types) is usually 180 parts by mass or more, preferably 1 part by mass of dimemorphan Is 184 parts by mass or more, more preferably 230 parts by mass or more, and most preferably 260 parts by mass or more. The blending amount of sucralose at this time is preferably 0.1 parts by mass or more per 1 part by mass of dimemorphan and / or a salt thereof (in the case of blending two or more).
本発明における「内服液剤」とは、内服することができる液体であれば特に制限はない。例えば内服液剤、ドリンク剤等の医薬品及び医薬部外品が挙げられる。また、「飲料」とは、栄養機能食品、特定保険用食品等の食品領域における各種飲料が挙げられる。
The “internal liquid” in the present invention is not particularly limited as long as it is a liquid that can be taken internally. Examples thereof include pharmaceuticals such as internal liquids and drinks and quasi drugs. In addition, “beverages” include various beverages in the food area such as nutritionally functional foods and foods for specified insurance.
本発明の内服液剤または飲料には、ビタミン、ミネラル、アミノ酸、生薬、生薬抽出物、カフェインなどを本発明の効果を損なわない範囲で適宜に配合できる。また、必要に応じて抗酸化剤、着色剤、香料、矯味剤、界面活性剤、溶解補助剤、保存剤、糖アルコール、トレハロース以外の甘味料、スクラロース以外の高甘味度甘味料などの添加物を本発明の効果を損なわない範囲で適宜に配合することもできる。これらの添加物等は、１種で単独に配合しても、２種以上を適宜組み合わせて配合してもよい。
In the internal use liquid or beverage of the present invention, vitamins, minerals, amino acids, herbal medicines, herbal extracts, caffeine, etc. can be appropriately blended within a range not impairing the effects of the present invention. In addition, additives such as antioxidants, coloring agents, flavoring agents, flavoring agents, surfactants, solubilizers, preservatives, sugar alcohols, sweeteners other than trehalose, and high-intensity sweeteners other than sucralose as necessary Can be appropriately blended within a range not impairing the effects of the present invention. These additives and the like may be blended singly or in combination of two or more.
本発明の内服液剤または飲料を調製する方法は特に限定されるものではない。通常、ジメモルファン及び／又はその塩、糖アルコール及び／又はトレハロース、スクラロース、及びその他に必要に応じて他の成分を適量の精製水で溶解した後、精製水をさらに加えて容量調整し、必要に応じて濾過、滅菌処理を施すことにより、ジメモルファン含有内服液剤または飲料として提供することができる。
The method for preparing the internal liquid or beverage of the present invention is not particularly limited. Usually, dimemorphan and / or its salt, sugar alcohol and / or trehalose, sucralose, and other ingredients as necessary are dissolved in a suitable amount of purified water, and then the volume is adjusted by adding further purified water. Accordingly, by performing filtration and sterilization treatment, it can be provided as a dimemorphan-containing internal solution or beverage.
以下に、試験例等を挙げ、本発明をさらに詳細に説明するが、本発明はこれらの試験例等に何ら限定されるものではない。
Hereinafter, the present invention will be described in more detail with reference to test examples and the like, but the present invention is not limited to these test examples and the like.
試験例
（１）各内服液剤または飲料の調製
下記に示す参考例１－３、実施例１－７及び比較例１－３の各内服液剤または飲料を調製した。 Test Example (1) Preparation of Each Internal Solution or Beverage Each internal solution or beverage of Reference Example 1-3, Example 1-7 and Comparative Example 1-3 shown below was prepared.
（１）各内服液剤または飲料の調製
下記に示す参考例１－３、実施例１－７及び比較例１－３の各内服液剤または飲料を調製した。 Test Example (1) Preparation of Each Internal Solution or Beverage Each internal solution or beverage of Reference Example 1-3, Example 1-7 and Comparative Example 1-3 shown below was prepared.
参考例１
ジメモルファンリン酸塩６０ｍｇ及びキシリトール１６０００ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Reference example 1
Dimemorphan phosphate 60 mg and xylitol 16000 mg were dissolved in purified water to a total volume of 40 mL.
ジメモルファンリン酸塩６０ｍｇ及びキシリトール１６０００ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Reference example 1
Dimemorphan phosphate 60 mg and xylitol 16000 mg were dissolved in purified water to a total volume of 40 mL.
参考例２
無水カフェイン３．３ｍｇ及びキシリトール１６０００ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Reference example 2
Anhydrous caffeine 3.3 mg and xylitol 16000 mg were dissolved in purified water to make a total volume of 40 mL.
無水カフェイン３．３ｍｇ及びキシリトール１６０００ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Reference example 2
Anhydrous caffeine 3.3 mg and xylitol 16000 mg were dissolved in purified water to make a total volume of 40 mL.
参考例３
ジメモルファンリン酸塩６０ｍｇ及びキシリトール１８０００ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Reference example 3
Dimemorphan phosphate 60 mg and xylitol 18000 mg were dissolved in purified water to a total volume of 40 mL.
ジメモルファンリン酸塩６０ｍｇ及びキシリトール１８０００ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Reference example 3
Dimemorphan phosphate 60 mg and xylitol 18000 mg were dissolved in purified water to a total volume of 40 mL.
実施例１
ジメモルファンリン酸塩６０ｍｇ、キシリトール１６０００ｍｇ及びスクラロース６．６ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Example 1
Dimemorphan phosphate 60 mg, xylitol 16000 mg and sucralose 6.6 mg were dissolved in purified water to make a total volume of 40 mL.
ジメモルファンリン酸塩６０ｍｇ、キシリトール１６０００ｍｇ及びスクラロース６．６ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Example 1
Dimemorphan phosphate 60 mg, xylitol 16000 mg and sucralose 6.6 mg were dissolved in purified water to make a total volume of 40 mL.
実施例２
ジメモルファンリン酸塩６０ｍｇ、ソルビトール１４０００ｍｇ及びスクラロース６．６ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Example 2
Dimemorphan phosphate 60 mg, sorbitol 14000 mg and sucralose 6.6 mg were dissolved in purified water to make a total volume of 40 mL.
ジメモルファンリン酸塩６０ｍｇ、ソルビトール１４０００ｍｇ及びスクラロース６．６ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Example 2
Dimemorphan phosphate 60 mg, sorbitol 14000 mg and sucralose 6.6 mg were dissolved in purified water to make a total volume of 40 mL.
実施例３
ジメモルファンリン酸塩６０ｍｇ、キシリトール１６０００ｍｇ、ステビア７．４ｍｇ及びスクラロース４．４ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Example 3
Dimemorphan phosphate 60 mg, xylitol 16000 mg, stevia 7.4 mg and sucralose 4.4 mg were dissolved in purified water to a total volume of 40 mL.
ジメモルファンリン酸塩６０ｍｇ、キシリトール１６０００ｍｇ、ステビア７．４ｍｇ及びスクラロース４．４ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Example 3
Dimemorphan phosphate 60 mg, xylitol 16000 mg, stevia 7.4 mg and sucralose 4.4 mg were dissolved in purified water to a total volume of 40 mL.
実施例４
ジメモルファンリン酸塩６０ｍｇ、エリスリトール８０００ｍｇ及びスクラロース４．４ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Example 4
Dimemorphan phosphate 60 mg, erythritol 8000 mg and sucralose 4.4 mg were dissolved in purified water to make a total volume of 40 mL.
ジメモルファンリン酸塩６０ｍｇ、エリスリトール８０００ｍｇ及びスクラロース４．４ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Example 4
Dimemorphan phosphate 60 mg, erythritol 8000 mg and sucralose 4.4 mg were dissolved in purified water to make a total volume of 40 mL.
実施例５
ジメモルファンリン酸塩６０ｍｇ、マルチトール１６０００ｍｇ及びスクラロース４．４ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Example 5
Dimemorphan phosphate 60 mg, maltitol 16000 mg and sucralose 4.4 mg were dissolved in purified water to make a total volume of 40 mL.
ジメモルファンリン酸塩６０ｍｇ、マルチトール１６０００ｍｇ及びスクラロース４．４ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Example 5
Dimemorphan phosphate 60 mg, maltitol 16000 mg and sucralose 4.4 mg were dissolved in purified water to make a total volume of 40 mL.
実施例６
ジメモルファンリン酸塩６０ｍｇ、トレハロース１６０００ｍｇ及びスクラロース４．４ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Example 6
Dimemorphan phosphate 60 mg, trehalose 16000 mg and sucralose 4.4 mg were dissolved in purified water to make a total volume of 40 mL.
ジメモルファンリン酸塩６０ｍｇ、トレハロース１６０００ｍｇ及びスクラロース４．４ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Example 6
Dimemorphan phosphate 60 mg, trehalose 16000 mg and sucralose 4.4 mg were dissolved in purified water to make a total volume of 40 mL.
実施例７
ジメモルファンリン酸塩６０ｍｇ、キシリトール４２００ｍｇ、ソルビトール１００８０ｍｇ、トレハロース１５００ｍｇ及びスクラロース１０．６ｍｇ、ステビア１７．７ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Example 7
Dimemorphan phosphate 60 mg, xylitol 4200 mg, sorbitol 10080 mg, trehalose 1500 mg and sucralose 10.6 mg, stevia 17.7 mg were dissolved in purified water to make a total volume of 40 mL.
ジメモルファンリン酸塩６０ｍｇ、キシリトール４２００ｍｇ、ソルビトール１００８０ｍｇ、トレハロース１５００ｍｇ及びスクラロース１０．６ｍｇ、ステビア１７．７ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Example 7
Dimemorphan phosphate 60 mg, xylitol 4200 mg, sorbitol 10080 mg, trehalose 1500 mg and sucralose 10.6 mg, stevia 17.7 mg were dissolved in purified water to make a total volume of 40 mL.
比較例１
ジメモルファンリン酸塩６０ｍｇ及びスクラロース３３．３ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Comparative Example 1
Dimemorphan phosphate 60 mg and sucralose 33.3 mg were dissolved in purified water to make a total volume of 40 mL.
ジメモルファンリン酸塩６０ｍｇ及びスクラロース３３．３ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Comparative Example 1
Dimemorphan phosphate 60 mg and sucralose 33.3 mg were dissolved in purified water to make a total volume of 40 mL.
比較例２
ジメモルファンリン酸塩６０ｍｇ及びステビア１１０．８ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Comparative Example 2
Dimemorphan phosphate 60 mg and stevia 110.8 mg were dissolved in purified water to a total volume of 40 mL.
ジメモルファンリン酸塩６０ｍｇ及びステビア１１０．８ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Comparative Example 2
Dimemorphan phosphate 60 mg and stevia 110.8 mg were dissolved in purified water to a total volume of 40 mL.
比較例３
ジメモルファンリン酸塩６０ｍｇ、キシリトール１６０００ｍｇ及びステビア２２ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Comparative Example 3
Dimemorphan phosphate 60 mg, xylitol 16000 mg and stevia 22 mg were dissolved in purified water to a total volume of 40 mL.
ジメモルファンリン酸塩６０ｍｇ、キシリトール１６０００ｍｇ及びステビア２２ｍｇを精製水に溶解し、全量を４０ｍＬとした。 Comparative Example 3
Dimemorphan phosphate 60 mg, xylitol 16000 mg and stevia 22 mg were dissolved in purified water to a total volume of 40 mL.
（２）試験方法
調製した各内服液剤または飲料を、表１の評価基準に基づき４名のパネルによる苦味及び喉への刺激の評価を実施し、結果を表２に示した。 (2) Test Method Each prepared liquid preparation or beverage was evaluated for bitterness and irritation by four panels based on the evaluation criteria shown in Table 1, and the results are shown in Table 2.
調製した各内服液剤または飲料を、表１の評価基準に基づき４名のパネルによる苦味及び喉への刺激の評価を実施し、結果を表２に示した。 (2) Test Method Each prepared liquid preparation or beverage was evaluated for bitterness and irritation by four panels based on the evaluation criteria shown in Table 1, and the results are shown in Table 2.
ここで甘味度（％）とは、
１００ｍＬ中のショ糖（砂糖）濃度［ｗ／ｖ％］
に相当する甘さとして定義され、甘味度１％とは、ショ糖１％水溶液の甘味度に相当する。
（３）結果 Here, sweetness (%)
Sucrose (sugar) concentration in 100 mL [w / v%]
The sweetness level of 1% corresponds to the sweetness level of a 1% sucrose aqueous solution.
(3) Results
１００ｍＬ中のショ糖（砂糖）濃度［ｗ／ｖ％］
に相当する甘さとして定義され、甘味度１％とは、ショ糖１％水溶液の甘味度に相当する。
（３）結果 Here, sweetness (%)
Sucrose (sugar) concentration in 100 mL [w / v%]
The sweetness level of 1% corresponds to the sweetness level of a 1% sucrose aqueous solution.
(3) Results
表２に示したように、参考例１、２の結果から、日本薬局方に苦味を有する薬物として記載されているカフェインを含有する飲料に糖アルコールを配合することで苦味を低減できたのに対し、ジメモルファンを含有する内服液剤に糖アルコールを配合しても、苦味を低減できないことがわかった。また、ジメモルファンを含有する飲料は、カフェインを含有する飲料よりも喉への刺激が強いことがわかった。
As shown in Table 2, from the results of Reference Examples 1 and 2, the bitterness could be reduced by adding sugar alcohol to the beverage containing caffeine described as a drug having a bitter taste in the Japanese Pharmacopoeia. On the other hand, it was found that the bitterness could not be reduced even when sugar alcohol was added to the oral solution containing dimemorphan. Moreover, it turned out that the drink containing a dimemorphan has the irritation | stimulation to a throat stronger than the drink containing a caffeine.
参考例３の結果から、ジメモルファンを含有する内服液剤または飲料に、糖アルコールをさらに配合し、甘味度を４５％に調整しても、参考例１と比較して苦味及び喉への刺激は低減されないことがわかった。
From the results of Reference Example 3, bitterness and throat irritation are reduced as compared with Reference Example 1 even when sugar alcohol is further added to an internal liquid or beverage containing dimemorphan and the sweetness is adjusted to 45%. I found out that it was not.
実施例１の結果から、ジメモルファン及び糖アルコールを配合した内服液剤に、スクラロースを同時に配合することで、苦味及び喉への刺激が低減されることがわかった。比較例１の結果から、ジメモルファンに糖アルコールは配合せずスクラロースを配合して実施例１と同等の甘味度に調整した場合は、喉への刺激は低減されるものの、苦味が低減されないことがわかった。同様に、比較例２の結果から、ジメモルファンにステビアを配合して実施例１と同等の甘味度に調整しても、苦味は低減されないことがわかった。
From the results of Example 1, it was found that bitterness and irritation to the throat were reduced by simultaneously blending sucralose with an internal solution containing dimethylmorphane and sugar alcohol. From the results of Comparative Example 1, when sucralose is added to dimemorphan and sucralose is added to adjust the sweetness to the same level as in Example 1, although irritation to the throat is reduced, bitterness may not be reduced. all right. Similarly, from the result of Comparative Example 2, it was found that bitterness was not reduced even when stevia was added to dimemorphan to adjust the sweetness to the same level as in Example 1.
また実施例２、４、５の結果から、糖アルコールとして実施例１で配合したキシリトールの代わりにソルビトール、エリスリトール、マルチトールを配合した場合も、ジメモルファンの苦味及び喉への刺激が低減されることがわかった。
In addition, from the results of Examples 2, 4, and 5, when sorbitol, erythritol, and maltitol are blended in place of the xylitol blended in Example 1 as a sugar alcohol, the bitter taste and irritation of throat are reduced. I understood.
また実施例６の結果から、実施例１、２、４、５で配合した糖アルコールの代わりにトレハロースを配合しても、ジメモルファンの苦味及び喉への刺激が低減されることがわかった。
Also, from the results of Example 6, it was found that even if trehalose was blended in place of the sugar alcohols blended in Examples 1, 2, 4, and 5, the bitter taste and throat irritation of dimethylmorphane were reduced.
実施例３の結果から、ジメモルファン、糖アルコール及びスクラロースを配合した内服液剤に、さらにステビアを配合しても、苦味及び喉への刺激は実施例１と同程度であり、配合可能であることがわかった。
From the results of Example 3, even if stevia is further added to the internal liquid preparation containing dimemorphan, sugar alcohol and sucralose, bitterness and irritation to the throat are similar to those in Example 1 and can be added. all right.
比較例３の結果から、実施例１で配合したスクラロースの代わりにステビアを配合した場合は、苦味及び喉への刺激は低減されないことがわかった。
From the results of Comparative Example 3, it was found that when stevia was blended instead of sucralose blended in Example 1, bitterness and throat irritation were not reduced.
本発明により、ジメモルファンを含有する飲料の苦味及び喉への刺激を低減することが可能となったので、商品性の高いジメモルファン含有飲料を医薬品、医薬部外品及び食品の分野において提供することができる。
According to the present invention, it has become possible to reduce the bitterness and irritation of the throat of a beverage containing dimethylmorphane, so that it is possible to provide a highly commercialized beverage containing dimethylmorphane in the fields of pharmaceuticals, quasi drugs and foods. it can.
Claims (3)
- ａ）ジメモルファン及び／又はその塩、ｂ）糖アルコール及び／又はトレハロース、ｃ）スクラロースを含有する内服液剤または飲料。 A) Dimemorphan and / or a salt thereof, b) a sugar alcohol and / or trehalose, c) an internal liquid or beverage containing sucralose.
- ａ）成分１質量部に対して、ｂ）成分が１８０質量部以上であり、かつｃ）成分が０．１質量部以上である請求項１に記載の内服液剤または飲料。 The internal liquid or beverage according to claim 1, wherein b) component is 180 parts by mass or more and c) component is 0.1 parts by mass or more with respect to 1 part by mass of a) component.
- 糖アルコールが、キシリトール、ソルビトール、エリスリトール及びマルチトールからなる群より選択される少なくとも１種である、請求項１又は２に記載の内服液剤または飲料。 The internal liquid or beverage according to claim 1 or 2, wherein the sugar alcohol is at least one selected from the group consisting of xylitol, sorbitol, erythritol, and maltitol.
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| JP2012517216A JP5928331B2 (en) | 2010-05-27 | 2011-05-13 | Dimemorphan-containing oral solution |
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| JP2010-121855 | 2010-05-27 | ||
| JP2010121855 | 2010-05-27 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015091779A (en) * | 2013-10-01 | 2015-05-14 | 大正製薬株式会社 | Oral liquid formulation |
| JP2015091778A (en) * | 2013-10-01 | 2015-05-14 | 大正製薬株式会社 | Oral liquid formulation |
| JP2016020331A (en) * | 2014-06-18 | 2016-02-04 | 大正製薬株式会社 | Solid formulations |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008260717A (en) * | 2007-04-12 | 2008-10-30 | Takada Seiyaku Kk | Masking agent for unpleasant taste, and oral composition with masked unpleasant taste |
| JP2009263298A (en) * | 2008-04-28 | 2009-11-12 | Ss Pharmaceut Co Ltd | Oral composition having masked disagreeable taste |
-
2011
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- 2011-05-13 WO PCT/JP2011/061024 patent/WO2011148794A1/en active Application Filing
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008260717A (en) * | 2007-04-12 | 2008-10-30 | Takada Seiyaku Kk | Masking agent for unpleasant taste, and oral composition with masked unpleasant taste |
| JP2009263298A (en) * | 2008-04-28 | 2009-11-12 | Ss Pharmaceut Co Ltd | Oral composition having masked disagreeable taste |
Non-Patent Citations (1)
| Title |
|---|
| HIROYUKI SUZUKI ET AL.: "Acetaminophen no Nigami Yokusei o Mokuteki to shita Keiko Seizai no Kento (2): Kizai Oyobi Kyomizai no Henko ni yoru Seizai no Kairyo", DAI 123 NENKAI THE PHARMACEUTICAL SOCIETY OF JAPAN KOEN YOSHISHU 4, vol. 28, no. P2, 5 March 2003 (2003-03-05), pages 109 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015091779A (en) * | 2013-10-01 | 2015-05-14 | 大正製薬株式会社 | Oral liquid formulation |
| JP2015091778A (en) * | 2013-10-01 | 2015-05-14 | 大正製薬株式会社 | Oral liquid formulation |
| JP2016020331A (en) * | 2014-06-18 | 2016-02-04 | 大正製薬株式会社 | Solid formulations |
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| JP5928331B2 (en) | 2016-06-01 |
| JPWO2011148794A1 (en) | 2013-07-25 |
| TW201208715A (en) | 2012-03-01 |
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