JP7118412B2 - バンコマイシン懸濁液充填カプセル製剤 - Google Patents
バンコマイシン懸濁液充填カプセル製剤 Download PDFInfo
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- JP7118412B2 JP7118412B2 JP2018142629A JP2018142629A JP7118412B2 JP 7118412 B2 JP7118412 B2 JP 7118412B2 JP 2018142629 A JP2018142629 A JP 2018142629A JP 2018142629 A JP2018142629 A JP 2018142629A JP 7118412 B2 JP7118412 B2 JP 7118412B2
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- suspension
- vancomycin
- vancomycin hydrochloride
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- capsule
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- 108010059993 Vancomycin Proteins 0.000 title claims description 75
- 239000000725 suspension Substances 0.000 title claims description 55
- 229960003165 vancomycin Drugs 0.000 title claims description 18
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 title claims description 18
- 239000007963 capsule composition Substances 0.000 title claims description 16
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 title description 18
- 229960001572 vancomycin hydrochloride Drugs 0.000 claims description 57
- LCTORFDMHNKUSG-XTTLPDOESA-N vancomycin monohydrochloride Chemical compound Cl.O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 LCTORFDMHNKUSG-XTTLPDOESA-N 0.000 claims description 57
- 239000007901 soft capsule Substances 0.000 claims description 41
- 239000000203 mixture Substances 0.000 claims description 33
- 239000007902 hard capsule Substances 0.000 claims description 31
- 238000009472 formulation Methods 0.000 claims description 28
- 239000002202 Polyethylene glycol Substances 0.000 claims description 20
- 229920001223 polyethylene glycol Polymers 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 14
- MYPYJXKWCTUITO-LYRMYLQWSA-O vancomycin(1+) Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C([O-])=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)[NH2+]C)[C@H]1C[C@](C)([NH3+])[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-O 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 25
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 23
- 238000004128 high performance liquid chromatography Methods 0.000 description 17
- 238000002156 mixing Methods 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000003860 storage Methods 0.000 description 14
- 108010010803 Gelatin Proteins 0.000 description 12
- 229920000159 gelatin Polymers 0.000 description 12
- 239000008273 gelatin Substances 0.000 description 12
- 235000019322 gelatine Nutrition 0.000 description 12
- 235000011852 gelatine desserts Nutrition 0.000 description 12
- 239000007788 liquid Substances 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 11
- 239000002775 capsule Substances 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000011049 filling Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 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 description 3
- 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 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 229920002556 Polyethylene Glycol 300 Polymers 0.000 description 3
- 229920002582 Polyethylene Glycol 600 Polymers 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 229960003511 macrogol Drugs 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- 229960002920 sorbitol Drugs 0.000 description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 2
- 108010025899 gelatin film Proteins 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 description 2
- 239000004014 plasticizer Substances 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 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 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 235000013878 L-cysteine Nutrition 0.000 description 1
- 239000004201 L-cysteine Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 1
- 239000004373 Pullulan Substances 0.000 description 1
- 229920001218 Pullulan Polymers 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 1
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011167 hydrochloric acid Nutrition 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000012931 lyophilized formulation Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 239000003910 polypeptide antibiotic agent Substances 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 238000013094 purity test Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
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- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
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Images
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
項1.
(A)バンコマイシン又はその塩、及び
(B)平均分子量300~500のポリエチレングリコール
を含む懸濁液が充填されたハード若しくはソフトカプセル製剤。
項2.
(B)成分が、平均分子量320~480のポリエチレングリコールである、項1に記載のカプセル製剤。
項3.
(A)成分が、バンコマイシン塩酸塩である、項1又は2に記載のカプセル製剤。
項4.
前記懸濁液が、実質的に水を含まない、項1~3のいずれかに記載のカプセル製剤。
項5.
前記懸濁液に含まれる(A)成分及び(B)成分の質量比が、1:0.1~3である、項1~4のいずれかに記載のカプセル製剤。
項6.
前記懸濁液が、(A)成分及び(B)成分のみからなる懸濁液である、項1~5のいずれかに記載のカプセル製剤。
項7.
(A)バンコマイシン塩酸塩、及び
(B)平均分子量320~480のポリエチレングリコール
のみからなり、(A)成分及び(B)成分の質量比が、1:0.1~3である懸濁液が充填されたハード若しくはソフトカプセル製剤。
M:本品の秤取量(g)
a:空試験における0.5mol/L水酸化ナトリウム液の消費量(mL)
b:被験物の試験における0.5mol/L水酸化ナトリウム液の消費量(mL)
また、ハードカプセルとソフトカプセルとは、第十七改正日本薬局方では、それぞれ硬カプセル、軟カプセルと規定されており、本発明もこれに従う。
バンコマイシン塩酸塩とPEG400とを、以下の質量比でバイアル瓶内で混合して懸濁液を調製した。
(参考例1)バンコマイシン塩酸塩:PEG400=5:1
(参考例2)バンコマイシン塩酸塩:PEG400=2:1
(参考例3)バンコマイシン塩酸塩:PEG400=1:1
(参考例4)バンコマイシン塩酸塩:PEG400=2:3
(参考例5)バンコマイシン塩酸塩:PEG400=1:2
(参考例6)バンコマイシン塩酸塩:PEG400=1:4
・移動相B:pH3.2トリエチルアミン緩衝液,アセトニトリル,テトラヒドロフラン(70:29:1)
・機器条件:送液速度1.5mL/min,波長280nm,サンプル投入量20μL
バンコマイシン塩酸塩と、次に示す各平均分子量のポリエチレングリコール(PEG300、PEG400、又はPEG600)とを、質量比2:3でバイアル瓶内で混合して懸濁液を調製した。
(参考例A)バンコマイシン塩酸塩:PEG300=2:3
(参考例B)バンコマイシン塩酸塩:PEG400=2:3
(参考例C)バンコマイシン塩酸塩:PEG600=2:3
(実施例1)
上記の検討において、最も保存性に優れた混合比率(バンコマイシン塩酸塩:PEG400=2:3)を採用し、当該質量比でこれらを混合した懸濁液をソフトカプセルに充填してソフトカプセル製剤を調製した。
(比較例1)
米国特許出願公開第2009/0232888号明細書の製剤3(表3)の即放部の組成を参考にして、バンコマイシン塩酸塩、PEG400、及びGelucireを質量比34:16:15で混合して混合液を調製し、これをゼラチンハードカプセルに充填してカプセル製剤を製造した(当該混合液200mg/1カプセル)。但し、Gelucireは湯浴で溶かした状態にしてから混合し、固まる前にカプセルに充填した。このため、充填後、常温になるとカプセル内の混合液は固体になった。
中国特許出願公開第101991557号明細書の実施例2の組成を参考にして、バンコマイシン塩酸塩、グリセリン、大豆油、PEG400、レシチン、及びL-システインを質量比25:3:10:40:5:1で混合して懸濁液を調製し、ゼラチンハードカプセルに充填してカプセル製剤を製造した(当該懸濁液200mg/1カプセル)。
用いたPEGをPEG400からPEG600へと変更した以外は、比較例2と同様にして、カプセル製剤を調製した。
国際公開第2001/047542号の実施例1の組成を参考にして、バンコマイシン塩酸塩を500mg、PEG400を100mg、精製水を5mL、混合し、当該混合液をバイアル充填した後、凍結乾燥して、凍結乾燥製剤を調製した。
さらにマンニトール100mgを加えて混合して混合液を調製したこと以外は、比較例4と同様にして、凍結乾燥製剤を調製した。(当該凍結乾燥製剤は、バンコマイシン塩酸塩散0.5g「MEEK」添付文書(第9版)に記載される市販品と同様の製剤と考えられる。)
上記ソフトカプセルの調製及び検討と同様に、バンコマイシン塩酸塩:PEG400=2:3の質量比でこれらを混合した懸濁液を、ハードカプセルに充填して、ハードカプセル製剤を調製した。
Claims (6)
- (A)バンコマイシン又はその塩、及び
(B)平均分子量300~500のポリエチレングリコール
を含み、実質的に水を含まない懸濁液が充填されたハード若しくはソフトカプセル製剤。 - (B)成分が、平均分子量320~480のポリエチレングリコールである、請求項1に記載のカプセル製剤。
- (A)成分が、バンコマイシン塩酸塩である、請求項1又は2に記載のカプセル製剤。
- 前記懸濁液に含まれる(A)成分及び(B)成分の質量比が、1:0.1~3である、請求項1~3のいずれかに記載のカプセル製剤。
- 前記懸濁液が、(A)成分及び(B)成分のみからなる懸濁液である、請求項1~4のいずれかに記載のカプセル製剤。
- (A)バンコマイシン塩酸塩、及び
(B)平均分子量320~480のポリエチレングリコール
のみからなり、(A)成分及び(B)成分の質量比が、1:0.1~3である懸濁液が充填されたハード若しくはソフトカプセル製剤。
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2000202003A (ja) | 1999-01-20 | 2000-07-25 | Shionogi Qualicaps Kk | 硬質カプセル及びその製造方法 |
JP2001170137A (ja) | 1999-12-16 | 2001-06-26 | Shionogi Qualicaps Kk | 硬質カプセル及びその製造方法 |
WO2004073692A1 (ja) | 2003-02-18 | 2004-09-02 | Yamashita, Shinji | 難水溶性薬物のハードカプセル剤 |
WO2016071495A1 (en) | 2014-11-06 | 2016-05-12 | Xellia Pharmaceuticals Aps | Glycopeptide compositions |
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JP2000202003A (ja) | 1999-01-20 | 2000-07-25 | Shionogi Qualicaps Kk | 硬質カプセル及びその製造方法 |
JP2001170137A (ja) | 1999-12-16 | 2001-06-26 | Shionogi Qualicaps Kk | 硬質カプセル及びその製造方法 |
WO2004073692A1 (ja) | 2003-02-18 | 2004-09-02 | Yamashita, Shinji | 難水溶性薬物のハードカプセル剤 |
WO2016071495A1 (en) | 2014-11-06 | 2016-05-12 | Xellia Pharmaceuticals Aps | Glycopeptide compositions |
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