JP5886147B2 - Pharmaceutical composition containing cetirizine hydrochloride and basic substance - Google Patents
Pharmaceutical composition containing cetirizine hydrochloride and basic substance Download PDFInfo
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- JP5886147B2 JP5886147B2 JP2012139680A JP2012139680A JP5886147B2 JP 5886147 B2 JP5886147 B2 JP 5886147B2 JP 2012139680 A JP2012139680 A JP 2012139680A JP 2012139680 A JP2012139680 A JP 2012139680A JP 5886147 B2 JP5886147 B2 JP 5886147B2
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- Prior art keywords
- cetirizine hydrochloride
- pharmaceutical composition
- magnesium
- tranexamic acid
- present
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- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 title claims description 31
- 229960004342 cetirizine hydrochloride Drugs 0.000 title claims description 31
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 17
- 239000000126 substance Substances 0.000 title description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 29
- 229960000401 tranexamic acid Drugs 0.000 claims description 28
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 claims description 28
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 19
- 235000012239 silicon dioxide Nutrition 0.000 claims description 16
- 239000000377 silicon dioxide Substances 0.000 claims description 12
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 claims description 7
- 239000000378 calcium silicate Substances 0.000 claims description 6
- 229910052918 calcium silicate Inorganic materials 0.000 claims description 6
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 claims description 6
- 229960001545 hydrotalcite Drugs 0.000 claims description 6
- 229910001701 hydrotalcite Inorganic materials 0.000 claims description 6
- 239000000395 magnesium oxide Substances 0.000 claims description 6
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 6
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 6
- WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical group [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 description 14
- 239000003826 tablet Substances 0.000 description 14
- 230000008859 change Effects 0.000 description 13
- 238000002156 mixing Methods 0.000 description 12
- 239000007787 solid Substances 0.000 description 11
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 239000000203 mixture Substances 0.000 description 9
- 239000006069 physical mixture Substances 0.000 description 9
- 238000002845 discoloration Methods 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 238000005469 granulation Methods 0.000 description 7
- 230000003179 granulation Effects 0.000 description 7
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
- 235000012241 calcium silicate Nutrition 0.000 description 5
- 239000001913 cellulose Substances 0.000 description 5
- 229920002678 cellulose Polymers 0.000 description 5
- 238000000975 co-precipitation Methods 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 229910052749 magnesium Inorganic materials 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 239000004033 plastic Substances 0.000 description 5
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 235000019700 dicalcium phosphate Nutrition 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 238000005550 wet granulation Methods 0.000 description 4
- 201000004624 Dermatitis Diseases 0.000 description 3
- 229940008027 aluminum hydroxide / magnesium carbonate Drugs 0.000 description 3
- 229940024546 aluminum hydroxide gel Drugs 0.000 description 3
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 3
- 239000000347 magnesium hydroxide Substances 0.000 description 3
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 3
- -1 magnesium metasilicate aluminate Chemical class 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 206010015150 Erythema Diseases 0.000 description 2
- 102000003834 Histamine H1 Receptors Human genes 0.000 description 2
- 108090000110 Histamine H1 Receptors Proteins 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 201000007100 Pharyngitis Diseases 0.000 description 2
- 208000003251 Pruritus Diseases 0.000 description 2
- 208000024780 Urticaria Diseases 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 229940024545 aluminum hydroxide Drugs 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229940124579 cold medicine Drugs 0.000 description 2
- JAUGGEIKQIHSMF-UHFFFAOYSA-N dialuminum;dimagnesium;dioxido(oxo)silane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O.[O-][Si]([O-])=O JAUGGEIKQIHSMF-UHFFFAOYSA-N 0.000 description 2
- PGZIKUPSQINGKT-UHFFFAOYSA-N dialuminum;dioxido(oxo)silane Chemical compound [Al+3].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O.[O-][Si]([O-])=O PGZIKUPSQINGKT-UHFFFAOYSA-N 0.000 description 2
- XLIDPNGFCHXNGX-UHFFFAOYSA-N dialuminum;oxygen(2-);silicon(4+) Chemical compound [O-2].[O-2].[O-2].[O-2].[O-2].[Al+3].[Al+3].[Si+4] XLIDPNGFCHXNGX-UHFFFAOYSA-N 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000007888 film coating Substances 0.000 description 2
- 238000009501 film coating Methods 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 229960002449 glycine Drugs 0.000 description 2
- 235000013905 glycine and its sodium salt Nutrition 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 230000033444 hydroxylation Effects 0.000 description 2
- 238000005805 hydroxylation reaction Methods 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 230000008676 import Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 2
- 239000001095 magnesium carbonate Substances 0.000 description 2
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 2
- ZADYMNAVLSWLEQ-UHFFFAOYSA-N magnesium;oxygen(2-);silicon(4+) Chemical compound [O-2].[O-2].[O-2].[Mg+2].[Si+4] ZADYMNAVLSWLEQ-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000011812 mixed powder Substances 0.000 description 2
- 239000000820 nonprescription drug Substances 0.000 description 2
- GRLPQNLYRHEGIJ-UHFFFAOYSA-J potassium aluminium sulfate Chemical compound [Al+3].[K+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O GRLPQNLYRHEGIJ-UHFFFAOYSA-J 0.000 description 2
- 229940088417 precipitated calcium carbonate Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 206010037844 rash Diseases 0.000 description 2
- 206010039083 rhinitis Diseases 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000004575 stone Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 1
- 101100083069 Candida albicans (strain SC5314 / ATCC MYA-2876) PGA62 gene Proteins 0.000 description 1
- 101100106993 Candida albicans (strain SC5314 / ATCC MYA-2876) YWP1 gene Proteins 0.000 description 1
- 208000019872 Drug Eruptions Diseases 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 101150054379 FLO1 gene Proteins 0.000 description 1
- 229940124056 Histamine H1 receptor antagonist Drugs 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 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 1
- HDVDLQFPDLTOSI-UHFFFAOYSA-L O[AlH]O Chemical compound O[AlH]O HDVDLQFPDLTOSI-UHFFFAOYSA-L 0.000 description 1
- 206010031009 Oral pain Diseases 0.000 description 1
- 206010068319 Oropharyngeal pain Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 150000004645 aluminates Chemical class 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- BWZOPYPOZJBVLQ-UHFFFAOYSA-K aluminium glycinate Chemical compound O[Al+]O.NCC([O-])=O BWZOPYPOZJBVLQ-UHFFFAOYSA-K 0.000 description 1
- 229940043673 aluminum hydroxide / calcium carbonate Drugs 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 229940030225 antihemorrhagics Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000003907 antipyretic analgesic agent Substances 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000005282 brightening Methods 0.000 description 1
- 229960003340 calcium silicate Drugs 0.000 description 1
- HFNQLYDPNAZRCH-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O.OC(O)=O HFNQLYDPNAZRCH-UHFFFAOYSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002826 coolant Substances 0.000 description 1
- 229940015826 dihydroxyaluminum aminoacetate Drugs 0.000 description 1
- 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 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- 230000003419 expectorant effect Effects 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000004088 foaming agent Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000002874 hemostatic agent Substances 0.000 description 1
- 239000000938 histamine H1 antagonist Substances 0.000 description 1
- 239000003317 industrial substance Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 208000018962 mouth sore Diseases 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229960004029 silicic acid Drugs 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 206010044008 tonsillitis Diseases 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
本発明は、セチリジン塩酸塩を含有する安定性に優れた医薬組成物に関するものである。 The present invention relates to a pharmaceutical composition containing cetirizine hydrochloride and excellent in stability.
セチリジン塩酸塩は、ａ）ヒスタミンＨ１受容体拮抗作用、ｂ）好酸球遊走抑制作用、ｃ）メディエータ遊離抑制作用を有し、本邦では、アレルギー性鼻炎、蕁麻疹、湿疹・皮膚炎、痒疹、皮膚掻痒症の効能・効果が認められている（例えば、非特許文献１参照）。
本邦では、上記のヒスタミンＨ１受容体拮抗作用を有する薬物は、一般用医薬品の感冒薬（かぜ薬）や鼻炎用内服薬の有効成分として、他の薬効を有する成分と配合されて市販されており、セチリジン塩酸塩に関しても、有効成分の一つとして期待されている。
Cetirizine hydrochloride has a) histamine H1 receptor antagonistic action, b) eosinophil migration inhibitory action, and c) mediator release inhibitory action. In Japan, allergic rhinitis, urticaria, eczema / dermatitis, rash, Efficacy and effect of cutaneous pruritus are recognized (for example, see Non-Patent Document 1).
In Japan, the above-mentioned drugs having histamine H1 receptor antagonism are marketed in combination with other medicinal ingredients as active ingredients for common cold drugs (cold medicines) and internal medicines for rhinitis, Cetirizine hydrochloride is also expected as one of the active ingredients.
トラネキサム酸は、抗プラスミン作用を有し、止血剤として広く用いられているほか、抗アレルギー作用及び抗炎症作用を有し、湿疹及びその類症、蕁麻疹、薬疹・中毒疹における紅斑・腫脹・そう痒等の症状；扁桃炎、咽喉頭炎における咽頭痛・発赤・充血・腫脹等の症状；口内炎における口内痛及び口内粘膜アフターに用いられている（例えば、非特許文献２参照）。 Tranexamic acid has antiplasmin activity, is widely used as a hemostatic agent, has anti-allergic and anti-inflammatory effects, erythema / swelling in eczema and related diseases, urticaria, drug eruption and poisoning eruption -Symptoms such as pruritus; symptoms such as sore throat, redness, hyperemia, swelling in tonsillitis and sore pharyngitis; used for mouth pain and mouth mucosa after in mouth sores (for example, see Non-Patent Document 2).
これまでに、ヒスタミンＨ１受容体拮抗薬や抗アレルギー薬と、トラネキサム酸との併用に関する報告は多数あるが（例えば、特許文献１、２参照）、セチリジン塩酸塩にトラネキサム酸を配合することによる製剤の安定性についての報告はない。 There have been many reports on the combined use of histamine H1 receptor antagonists and antiallergic drugs and tranexamic acid so far (see, for example, Patent Documents 1 and 2), but a preparation by combining tranexamic acid with cetirizine hydrochloride There is no report on the stability of.
本発明者らは、セチリジン塩酸塩とトラネキサム酸を混合、保存した際、経時的な変色や性状変化が発生することを見出した。それらの変化を避けるためには、一般的には、セチリジン塩酸塩とトラネキサム酸を接触（混合）させないこと、例えば、セチリジン塩酸塩とトラネキサム酸を、各々別顆粒に配合すればよいが、かかる方法では、製剤の製造工程が多くなり、製造コストが増加する。
本発明の課題は、かかるセチリジン塩酸塩とトラネキサム酸の配合変化を、より簡便に防止する方法を提供することである。
The present inventors have found that when cetirizine hydrochloride and tranexamic acid are mixed and stored, discoloration and property changes with time occur. In order to avoid these changes, generally, cetirizine hydrochloride and tranexamic acid are not brought into contact (mixed), for example, cetirizine hydrochloride and tranexamic acid may be blended in separate granules. Then, the manufacturing process of a formulation increases and manufacturing cost increases.
The subject of this invention is providing the method of preventing the mixing | blending change of this cetirizine hydrochloride and tranexamic acid more simply.
本発明者らは、かかる配合変化を防止するために鋭意研究を進めたところ、セチリジン塩酸塩及びトラネキサム酸に、さらに、塩基性医薬品添加物及び／又は含水二酸化ケイ素を配合することにより、セチリジン塩酸塩とトラネキサム酸を配合した際の変色、性状変化を防止できることを見出し、本発明を完成させた。 The inventors of the present invention have made extensive studies in order to prevent such a change in formulation, and by adding a basic pharmaceutical additive and / or hydrous silicon dioxide to cetirizine hydrochloride and tranexamic acid, cetirizine hydrochloride The present inventors have found that discoloration and property change can be prevented when a salt and tranexamic acid are blended, and the present invention has been completed.
すなわち、本発明は以下の（１）〜（４）を提供するものである。
（１）セチリジン塩酸塩、トラネキサム酸、並びに塩基性医薬品添加物及び／又は含水二酸化ケイ素を含有する医薬組成物。
（２）塩基性医薬品添加物が、乾燥水酸化アルミニウムゲル、ケイ酸アルミン酸マグネシウム、ケイ酸マグネシウム、合成ケイ酸アルミニウム、合成ヒドロタルサイト、酸化マグネシウム、水酸化アルミナマグネシウム、水酸化アルミニウムゲル、水酸化アルミニウム・炭酸水素ナトリウム共沈生成物、水酸化アルミニウム・炭酸マグネシウム混合乾燥ゲル、水酸化アルミニウム・炭酸マグネシウム・炭酸カルシウム共沈生成物、水酸化マグネシウム、炭酸マグネシウム、沈降炭酸カルシウム、メタケイ酸アルミン酸マグネシウム、無水リン酸水素カルシウム、リン酸水素カルシウム、烏賊骨、石決明、ボレイ、軽質無水ケイ酸、重質無水ケイ酸、ケイ酸カルシウム、アミノ酢酸、ジヒドロキシアルミニウム・アミノ酢酸塩、及び水酸化マグネシウム・硫酸アルミニウムカリウム共沈生成物から選ばれる１種以上である、（１）に記載の医薬組成物。
（３）塩基性医薬品添加物が、メタケイ酸アルミン酸マグネシム、合成ヒドロタルサイト、酸化マグネシウム、及びケイ酸カルシウムから選ばれる１種以上である、（１）に記載の医薬組成物。
（４）剤形が固形製剤である、（１）〜（３）のいずれか１に記載の医薬組成物。
That is, the present invention provides the following (1) to (4).
(1) A pharmaceutical composition containing cetirizine hydrochloride, tranexamic acid, a basic pharmaceutical additive and / or hydrous silicon dioxide.
(2) Basic pharmaceutical additive is dry aluminum hydroxide gel, magnesium aluminate silicate, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, magnesium alumina hydroxide, aluminum hydroxide gel, water Aluminum oxide / sodium bicarbonate coprecipitation product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate coprecipitation product, magnesium hydroxide, magnesium carbonate, precipitated calcium carbonate, metasilicate aluminate Magnesium, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, bandit bone, stone decision, volley, light anhydrous silicic acid, heavy anhydrous silicic acid, calcium silicate, aminoacetic acid, dihydroxyaluminum aminoacetate, and hydroxylation Mug Is at least one selected from the Siumu Aluminum sulfate Potassium coprecipitated product, pharmaceutical composition according to (1).
(3) The pharmaceutical composition according to (1), wherein the basic pharmaceutical additive is at least one selected from magnesium aluminometasilicate, synthetic hydrotalcite, magnesium oxide, and calcium silicate.
(4) The pharmaceutical composition according to any one of (1) to (3), wherein the dosage form is a solid preparation.
本発明により、セチリジン塩酸塩及びトラネキサム酸を含有する、安定した医薬組成物を提供することができる。 According to the present invention, a stable pharmaceutical composition containing cetirizine hydrochloride and tranexamic acid can be provided.
本発明の医薬組成物は、セチリジン塩酸塩とトラネキサム酸とを含有する医薬組成物に、安定剤として塩基性医薬品添加物及び／又は含水二酸化ケイ素を添加することにより、セチリジン塩酸塩とトラネキサム酸とが互いに境界膜等を有さずに混合して存在しても変色せずに安定に存在することを特徴とする。 The pharmaceutical composition of the present invention comprises cetirizine hydrochloride and tranexamic acid by adding a basic pharmaceutical additive and / or hydrous silicon dioxide as a stabilizer to a pharmaceutical composition containing cetirizine hydrochloride and tranexamic acid. Are stable without discoloration even if they are mixed without having a boundary film or the like.
本発明に用いられる「セチリジン塩酸塩」、「トラネキサム酸」は第１５改正日本薬局方に収載されている。 “Cetirizine hydrochloride” and “tranexamic acid” used in the present invention are listed in the 15th revised Japanese Pharmacopoeia.
本発明に用いられる「塩基性医薬品添加物」とは、５％懸濁液のｐＨが７以上のケイ酸類、もしくは一般用医薬品製造（輸入）承認基準（２０００年度版）のかぜ薬、解熱鎮痛薬、及び鎮咳去痰薬の一般用医薬品製造（輸入）承認基準に収載されている胃粘膜保護成分（胃粘膜保護成分とは第１５改正日本薬局方に収載されている制酸力試験法で制酸力を示す）添加物で、具体的には、乾燥水酸化アルミニウムゲル、ケイ酸アルミン酸マグネシウム、ケイ酸マグネシウム、合成ケイ酸アルミニウム、合成ヒドロタルサイト、酸化マグネシウム、水酸化アルミナマグネシウム、水酸化アルミニウムゲル、水酸化アルミニウム・炭酸水素ナトリウム共沈生成物、水酸化アルミニウム・炭酸マグネシウム混合乾燥ゲル、水酸化アルミニウム・炭酸マグネシウム・炭酸カルシウム共沈生成物、水酸化マグネシウム、炭酸マグネシウム、沈降炭酸カルシウム、メタケイ酸アルミン酸マグネシウム、無水リン酸水素カルシウム、リン酸水素カルシウム、烏賊骨、石決明、ボレイ、軽質無水ケイ酸、重質無水ケイ酸、ケイ酸カルシウム、アミノ酢酸、ジヒドロキシアルミニウム・アミノ酢酸塩、及び水酸化マグネシウム・硫酸アルミニウムカリウム共沈生成物等であり、一般用医薬品製造（輸入）承認基準（２０００年度版）、２００７医薬品添加物事典、及び２００７医薬品添加物ハンドブックに収載されている。本発明における塩基性医薬品添加物としては、メタケイ酸アルミン酸マグネシム、合成ヒドロタルサイト、酸化マグネシウム、及びケイ酸カルシウムから選ばれる１種以上であることが好ましい。 The “basic pharmaceutical additive” used in the present invention is a silicic acid having a 5% suspension having a pH of 7 or higher, or a cold medicine and antipyretic analgesic approved by the manufacturing (import) standard for over-the-counter drugs (2000 version). Gastric mucosal protective ingredients listed in the standard for the manufacture and import of over-the-counter drugs for drugs and antitussive expectorant (the gastric mucosa protective ingredients are controlled by the antacid test method listed in the 15th revised Japanese Pharmacopoeia. Additives that show acidity), specifically, dry aluminum hydroxide gel, magnesium aluminate silicate, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, magnesium alumina hydroxide, hydroxylation Aluminum gel, aluminum hydroxide / sodium bicarbonate coprecipitation product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / carbonate carbonate Nesium-calcium carbonate coprecipitation product, magnesium hydroxide, magnesium carbonate, precipitated calcium carbonate, magnesium metasilicate aluminate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, bandit bone, stone decision, volley, light anhydrous silicic acid , Heavy anhydrous silicic acid, calcium silicate, aminoacetic acid, dihydroxyaluminum / aminoacetate, and magnesium hydroxide / potassium aluminum sulfate coprecipitation products, etc. ), 2007 Pharmaceutical Additives Encyclopedia, and 2007 Pharmaceutical Additives Handbook. The basic pharmaceutical additive in the present invention is preferably at least one selected from magnesium aluminometasilicate, synthetic hydrotalcite, magnesium oxide, and calcium silicate.
本発明における「含水二酸化ケイ素」としては、２００７医薬品添加物事典に収載されているものを使用すればよいが、特に多孔性で給油能がすぐれていることが特徴とされているグレードのものが望ましく、例えば、アドソリダー（登録商標）１０２（フロイント産業）、カープレックス（登録商標）♯６７（ＤＳＬ．ジャパン）、カープレックス（登録商標）♯８０（ＤＳＬ．ジャパン）、含水二酸化ケイ素（東ソー・シリカ）等が挙げられる。 As the “hydrated silicon dioxide” in the present invention, those listed in the 2007 Pharmaceutical Additives Encyclopedia may be used. Desirable, for example, Adsolider (registered trademark) 102 (Freund Sangyo), Carplex (registered trademark) # 67 (DSL. Japan), Carplex (registered trademark) # 80 (DSL. Japan), hydrous silicon dioxide (Tosoh Silica) ) And the like.
本発明の医薬組成物の剤形は、本発明の効果が奏される限り特に限定されないが、固形製剤または液剤が好ましく、固形製剤であることがより好ましい。本発明における固形製剤とは、例えば、第１５改正日本薬局方に記載されている顆粒剤、散剤、カプセル剤、錠剤、または丸剤等を挙げることができ、好適には、顆粒剤、散剤、カプセル剤又は錠剤である。また、本発明における液剤とは、例えば、第１５改正日本薬局方に記載されている液剤、エアゾール剤、点眼剤等を挙げることができる。
また、本発明の剤形が顆粒剤又は錠剤の場合、その態様として、水溶性の高分子などで製剤をコーティングしたものや、糖で錠剤をコーティングしたものも好適である。すなわち、フィルムコーティング顆粒、フィルムコーティング錠、糖衣錠等が挙げられる。
くわえて、本発明の剤形が錠剤の場合、組成の異なる粉末又は顆粒を２層又は３層以上に積み重ねて圧縮成型した多層錠も好ましい態様として挙げられる。
本発明の医薬組成物における、セチリジン塩酸塩とトラネキサム酸、塩基性医薬品添加物及び／又は含水二酸化ケイ素の含有比は、セチリジン塩酸塩１重量部あたり、それぞれ、１０〜１５０重量部、１〜５００重量部であり、好ましくは、１０〜１００重量部、１〜４００重量部である。
The dosage form of the pharmaceutical composition of the present invention is not particularly limited as long as the effects of the present invention are exhibited, but a solid preparation or a liquid preparation is preferable, and a solid preparation is more preferable. Examples of the solid preparation in the present invention include granules, powders, capsules, tablets, pills and the like described in the 15th revised Japanese Pharmacopoeia, preferably, granules, powders, Capsule or tablet. Examples of the liquid agent in the present invention include liquid agents, aerosol agents, eye drops and the like described in the 15th revised Japanese pharmacopoeia.
Moreover, when the dosage form of the present invention is a granule or a tablet, a form in which the preparation is coated with a water-soluble polymer or a form in which a tablet is coated with sugar is also suitable. That is, a film coating granule, a film coating tablet, a sugar-coated tablet, etc. are mentioned.
In addition, when the dosage form of the present invention is a tablet, a multilayer tablet obtained by compressing and molding powders or granules having different compositions in two layers or three or more layers is also mentioned as a preferred embodiment.
The content ratio of cetirizine hydrochloride and tranexamic acid, basic pharmaceutical additive and / or hydrous silicon dioxide in the pharmaceutical composition of the present invention is 10 to 150 parts by weight and 1 to 500 parts per 1 part by weight of cetirizine hydrochloride, respectively. Parts by weight, preferably 10 to 100 parts by weight, and 1 to 400 parts by weight.
本発明の医薬組成物における製剤の製造方法としては、セチリジン塩酸塩、トラネキサム酸、並びに塩基性医薬品添加物及び／又は含水二酸化ケイ素が均一に混合する工程が含まれていれば、特に制限はない。ここで、「均一に混合する」とは、セチリジン塩酸塩、トラネキサム酸、及び塩基性医薬品添加物を、通常使用される混合機、例えば攪拌型混合機等により混合すればよい。 The method for producing the preparation in the pharmaceutical composition of the present invention is not particularly limited as long as it includes a step of uniformly mixing cetirizine hydrochloride, tranexamic acid, and a basic pharmaceutical additive and / or hydrous silicon dioxide. . Here, “mixing uniformly” means mixing cetirizine hydrochloride, tranexamic acid, and basic pharmaceutical additives with a commonly used mixer such as a stirring mixer.
本発明の医薬組成物の剤形が固形製剤の場合、かかる固形製剤の製造方法としては、セチリジン塩酸塩、トラネキサム酸、並びに塩基性医薬品添加物及び／又は含水二酸化ケイ素を含む組成物を造粒するのが好ましい。かかる造粒としては、乾式造粒や湿式造粒が挙げられるが、本発明においては、湿式造粒が好ましい。本発明にかかる固形製剤を製造する際の湿式造粒としては、攪拌造粒、噴霧造粒、転動造粒、流動層造粒、押し出し造粒等の通常に医薬品等の分野で使用されている湿式造粒法であれば、特に限定されない。
さらに本発明においては、前記造粒によって得られた造粒物を圧縮成型し、錠剤とするのが好ましい。
When the dosage form of the pharmaceutical composition of the present invention is a solid preparation, a method for producing such a solid preparation includes granulating a composition containing cetirizine hydrochloride, tranexamic acid, a basic pharmaceutical additive and / or hydrous silicon dioxide. It is preferable to do this. Examples of such granulation include dry granulation and wet granulation. In the present invention, wet granulation is preferable. As the wet granulation in producing the solid preparation according to the present invention, it is usually used in the field of pharmaceuticals such as stirring granulation, spray granulation, tumbling granulation, fluidized bed granulation, extrusion granulation and the like. The wet granulation method is not particularly limited.
Furthermore, in the present invention, the granulated product obtained by the granulation is preferably compression-molded to form a tablet.
本発明における固形製剤の調製する際には、必要により他の薬効成分を配合し、さらに必要に応じて、前記に挙げられた塩基性医薬品添加物及び／又は含水二酸化ケイ素以外の製剤添加剤を添加して、調製してもよい。本発明にかかる固形製剤の製剤化に使用される製剤添加剤としては、薬学的に許容される担体、例えば賦形剤、結合剤、崩壊剤、崩壊補助剤、滑沢剤、流動化剤、光沢化剤、発砲剤、防湿剤、界面活性剤、安定化剤、乳化剤、抗酸化剤、充填剤、防腐剤、保存剤、甘味剤、矯味剤、清涼化剤、香料、芳香剤、着色剤、基剤、コーティング剤、糖衣剤、可塑剤、分散剤、消泡剤等が挙げられ、従来公知の固形製剤に使用しうる製剤添加剤を上記の目的で使用し得る。 When preparing the solid preparation of the present invention, other medicinal ingredients are blended as necessary, and if necessary, preparation additives other than the basic pharmaceutical additives and / or hydrous silicon dioxide listed above are added. You may add and prepare. The formulation additive used for formulating the solid formulation according to the present invention includes a pharmaceutically acceptable carrier such as an excipient, a binder, a disintegrant, a disintegration aid, a lubricant, a fluidizing agent, Brightening agents, foaming agents, moisture-proofing agents, surfactants, stabilizers, emulsifiers, antioxidants, fillers, preservatives, preservatives, sweeteners, flavoring agents, cooling agents, fragrances, fragrances, colorants , Bases, coating agents, dragees, plasticizers, dispersants, antifoaming agents and the like, and conventionally known formulation additives that can be used for solid formulations can be used for the above purpose.
本発明をより詳細に説明するため、以下に実施例及び比較例を記載するが、本発明はこれらに限定されるものではない。 In order to describe the present invention in more detail, examples and comparative examples are described below, but the present invention is not limited thereto.
試験例：安定化剤の比較試験
（比較例１)
セチリジン塩酸塩（パーマケム・アジア）１．０ｇとトラネキサム酸（第一三共プロファーマ）１０．０ｇをポリ袋にて混合した後に、混合末を篩（２０号）にて篩過し物理混合物を得た。
Test example: Stabilizer comparison test (Comparative Example 1)
After mixing 1.0 g of cetirizine hydrochloride (Permachem Asia) and 10.0 g of tranexamic acid (Daiichi Sankyo Propharma) in a plastic bag, the mixed powder is sieved with a sieve (No. 20) to obtain a physical mixture. Obtained.
（比較例２)
セチリジン塩酸塩１．０ｇ、トラネキサム酸１０．０ｇ、及びｄｌ−リンゴ酸（扶桑化学工業）１．０ｇをポリ袋にて混合した後に、混合末を篩（２０号）にて篩過し物理混合物を得た。
(Comparative Example 2)
After mixing 1.0 g of cetirizine hydrochloride, 10.0 g of tranexamic acid, and 1.0 g of dl-malic acid (Fuso Chemical Co., Ltd.) in a plastic bag, the mixed powder is sieved with a sieve (No. 20) to obtain a physical mixture. Got.
（実施例１）
セチリジン塩酸塩３．０ｇ、トラネキサム酸３０．０ｇ、メタケイ酸アルミン酸マグネシウム（富士化学工業）３．０ｇ、結晶セルロース適量をポリ袋に投入・混合し物理混合物を調製した。その後、物理混合物にステアリン酸マグネシウム０．５ｇを混合・打錠して裸錠を調製した。
Example 1
A physical mixture was prepared by charging and mixing 3.0 g of cetirizine hydrochloride, 30.0 g of tranexamic acid, 3.0 g of magnesium aluminate metasilicate (Fuji Chemical Industry), and an appropriate amount of crystalline cellulose into a plastic bag. Thereafter, 0.5 g of magnesium stearate was mixed with the physical mixture and tableted to prepare a plain tablet.
（実施例２）
セチリジン塩酸塩３．０ｇ、トラネキサム酸３０．０ｇ、酸化マグネシウム（協和化学工業）３．０ｇ、結晶セルロース適量をポリ袋に投入・混合し物理混合物を調製した。その後、物理混合物にステアリン酸マグネシウム０．５ｇを混合・打錠して裸錠を調製した。
(Example 2)
A physical mixture was prepared by charging and mixing 3.0 g of cetirizine hydrochloride, 30.0 g of tranexamic acid, 3.0 g of magnesium oxide (Kyowa Chemical Industry), and an appropriate amount of crystalline cellulose into a plastic bag. Thereafter, 0.5 g of magnesium stearate was mixed with the physical mixture and tableted to prepare a plain tablet.
（実施例３）
セチリジン塩酸塩３．０ｇ、トラネキサム酸３０．０ｇ、合成ヒドロタルサイト（協和化学工業）３．０ｇ、結晶セルロース適量をポリ袋に投入・混合し物理混合物を調製した。その後、物理混合物にステアリン酸マグネシウム０．５ｇを混合・打錠して裸錠を調製した。
(Example 3)
A physical mixture was prepared by charging and mixing 3.0 g of cetirizine hydrochloride, 30.0 g of tranexamic acid, 3.0 g of synthetic hydrotalcite (Kyowa Chemical Industry), and an appropriate amount of crystalline cellulose into a plastic bag. Thereafter, 0.5 g of magnesium stearate was mixed with the physical mixture and tableted to prepare a plain tablet.
（実施例４）
セチリジン塩酸塩２．５ｇ、トラネキサム酸２００．０ｇ、メタケイ酸アルミン酸マグネシウム２００．０ｇ、結晶セルロース適量を流動層造粒機（フローコーター（型式ＦＬＯ１）：フロイント産業化式会社製）に投入・流動化後に、ヒドロキシプロピルセルロースを噴霧し造粒物を調製した。調製した造粒物４９．５ｇにステアリン酸マグネシウム０．５ｇを混合・打錠して裸錠を調製した。
Example 4
Cetirizine hydrochloride 2.5g, tranexamic acid 200.0g, magnesium metasilicate aluminate 200.0g, crystalline cellulose appropriate amount are put into a fluidized bed granulator (flow coater (model FLO1) manufactured by Freund Industrial Chemical Company) and fluidized. After conversion, hydroxypropylcellulose was sprayed to prepare a granulated product. A plain tablet was prepared by mixing and tableting 49.5 g of the prepared granulated product with 0.5 g of magnesium stearate.
（実施例５）
セチリジン塩酸塩２．５ｇ、トラネキサム酸２００．０ｇ、ケイ酸カルシウム（エーザイフード・ケミカル）５０．０ｇ、結晶セルロース適量を流動層造粒機に投入・流動化後に、ヒドロキシプロピルセルロースを噴霧し造粒物を調製した。調製した造粒物４９．５ｇにステアリン酸マグネシウム０．５ｇを混合・打錠して裸錠を調製した。
(Example 5)
Cetirizine hydrochloride 2.5 g, tranexamic acid 200.0 g, calcium silicate (Eisai Food Chemical) 50.0 g, appropriate amount of crystalline cellulose is put into a fluidized bed granulator and fluidized, then hydroxypropylcellulose is sprayed and granulated A product was prepared. A plain tablet was prepared by mixing and tableting 49.5 g of the prepared granulated product with 0.5 g of magnesium stearate.
１．試験方法
比較例１の物理混合物及び実施例１−３の錠剤をガラス瓶（４ｋ規格瓶）に充填し４０℃７５％開放、及び５０℃開放の条件で２ヶ月間放置した。保管後に冷蔵庫保存品を対照として色調変化、性状変化を確認した。また、変色の度合いに関しては色差計（分光式色差計（型式ＳＥ２０００）：日本電色工業製）にて各サンプルのＬ＊、ａ＊、ｂ＊の値を測定し、保管前と保管後のサンプル間のΔＥ（Ｌ＊ａ＊ｂ＊表色系での座標間距離で定義される値）を算出した。色差計にて測定した。
1. Test Method The physical mixture of Comparative Example 1 and the tablet of Example 1-3 were filled in a glass bottle (4k standard bottle) and left for 2 months under the conditions of 40 ° C 75% open and 50 ° C open. After storage, the color change and property change were confirmed using the refrigerator stored product as a control. Regarding the degree of discoloration, the L * , a * , b * values of each sample were measured with a color difference meter (spectral color difference meter (model SE2000): manufactured by Nippon Denshoku Industries Co., Ltd.) before and after storage. ΔE between samples (L * a * b * value defined by distance between coordinates in the color system) was calculated. Measured with a color difference meter.
色調変化の評価は、Ａ：変色なし、Ｂ：わずかな変色、Ｃ：変色あり、Ｄ：著しい変色、の４段階である。
性状変化の評価は、Ａ：変化なし、Ｂ：わずかな変化、Ｃ：変化あり、Ｄ：著しい変化、の４段階である。
The evaluation of the change in color tone has four stages: A: no discoloration, B: slight discoloration, C: discoloration, and D: significant discoloration.
The evaluation of property change is in four stages: A: no change, B: slight change, C: change, D: significant change.
２．試験結果
表２及び表３の結果より、セチリジン塩酸塩、トラネキサム酸が均一に存在してなる組成物に、塩基性医薬品添加物又は含水二酸化ケイ素を添加した場合には、色調変化、性状変化が著しく抑制できる固形製剤を製造できることがわかった。
2. Test results From the results of Tables 2 and 3, when a basic pharmaceutical additive or hydrous silicon dioxide was added to a composition in which cetirizine hydrochloride and tranexamic acid were uniformly present, there was a change in color tone and a change in properties. It was found that a solid preparation that can be significantly suppressed can be produced.
本発明により、セチリジン塩酸塩とトラネキサム酸を含有する医薬組成物を、簡便かつ低コストに製造することができる。かかる医薬組成物は、感冒や鼻炎等の治療に利用できるので、有用である。 According to the present invention, a pharmaceutical composition containing cetirizine hydrochloride and tranexamic acid can be produced simply and at low cost. Such a pharmaceutical composition is useful because it can be used for the treatment of colds and rhinitis.
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