CN1384745A - 含有一种氟喹诺酮抗生素和黄原酸胶的药物组合物 - Google Patents
含有一种氟喹诺酮抗生素和黄原酸胶的药物组合物 Download PDFInfo
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- xanthan gum
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- 239000000230 xanthan gum Substances 0.000 title claims abstract description 36
- 229920001285 xanthan gum Polymers 0.000 title claims abstract description 36
- 229940082509 xanthan gum Drugs 0.000 title claims abstract description 36
- 235000010493 xanthan gum Nutrition 0.000 title claims abstract description 36
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 13
- 239000003306 quinoline derived antiinfective agent Substances 0.000 title claims abstract description 13
- 239000003814 drug Substances 0.000 title abstract description 16
- 229940079593 drug Drugs 0.000 title abstract 3
- 159000000007 calcium salts Chemical class 0.000 claims abstract description 12
- 239000000203 mixture Substances 0.000 claims description 34
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 claims description 25
- 229960003405 ciprofloxacin Drugs 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical group [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 8
- 239000001110 calcium chloride Substances 0.000 claims description 8
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 8
- 235000011148 calcium chloride Nutrition 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 150000001768 cations Chemical class 0.000 claims description 6
- 239000011575 calcium Substances 0.000 claims description 3
- BCZXFFBUYPCTSJ-UHFFFAOYSA-L Calcium propionate Chemical compound [Ca+2].CCC([O-])=O.CCC([O-])=O BCZXFFBUYPCTSJ-UHFFFAOYSA-L 0.000 claims description 2
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 claims description 2
- 239000001639 calcium acetate Substances 0.000 claims description 2
- 235000011092 calcium acetate Nutrition 0.000 claims description 2
- 229960005147 calcium acetate Drugs 0.000 claims description 2
- 239000011692 calcium ascorbate Substances 0.000 claims description 2
- 235000010376 calcium ascorbate Nutrition 0.000 claims description 2
- 229940047036 calcium ascorbate Drugs 0.000 claims description 2
- 229960002713 calcium chloride Drugs 0.000 claims description 2
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 claims description 2
- 239000001527 calcium lactate Substances 0.000 claims description 2
- 235000011086 calcium lactate Nutrition 0.000 claims description 2
- 229960002401 calcium lactate Drugs 0.000 claims description 2
- 239000004330 calcium propionate Substances 0.000 claims description 2
- 235000010331 calcium propionate Nutrition 0.000 claims description 2
- BLORRZQTHNGFTI-ZZMNMWMASA-L calcium-L-ascorbate Chemical compound [Ca+2].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] BLORRZQTHNGFTI-ZZMNMWMASA-L 0.000 claims description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 229940124307 fluoroquinolone Drugs 0.000 description 9
- 238000005352 clarification Methods 0.000 description 8
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- KHSLHYAUZSPBIU-UHFFFAOYSA-M benzododecinium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 KHSLHYAUZSPBIU-UHFFFAOYSA-M 0.000 description 6
- 229940073464 benzododecinium bromide Drugs 0.000 description 6
- 229920001214 Polysorbate 60 Polymers 0.000 description 5
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
- 230000036571 hydration Effects 0.000 description 4
- 238000006703 hydration reaction Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000001632 sodium acetate Substances 0.000 description 4
- 235000017281 sodium acetate Nutrition 0.000 description 4
- VGTPKLINSHNZRD-UHFFFAOYSA-N oxoborinic acid Chemical compound OB=O VGTPKLINSHNZRD-UHFFFAOYSA-N 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 238000005498 polishing Methods 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- PDFKFLNYRFAWOA-UHFFFAOYSA-N 1-fluoroquinolin-2-one Chemical compound C1=CC=C2C=CC(=O)N(F)C2=C1 PDFKFLNYRFAWOA-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 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
- 229930195725 Mannitol Natural products 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229960005475 antiinfective agent Drugs 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960005069 calcium Drugs 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000004531 microgranule Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 238000010935 polish filtration Methods 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
-
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
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- A—HUMAN NECESSITIES
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- A61P31/04—Antibacterial agents
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- A61K9/00—Medicinal preparations characterised by special physical form
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Abstract
本发明公开了一种药物组合物,该组合物含有一种氟喹诺酮抗生素、黄原酸胶和一种足量的能够使氟喹诺酮抗生素和黄原酸胶相配伍的水溶性钙盐。
Description
发明背景
1.发明领域
本发明涉及药物组合物。特别地，本发明涉及的药物组合物中用于组方的氟喹诺酮(fluroquinolone)抗生素和黄原酸胶是可配伍的。
2.相关技术的描述
黄原酸胶是一种已知作为粘度增强剂用于眼药组合物的多糖。美国专利No.4,136,177公开的眼药组合物包括一种眼药和浓度约为自0.01至2.5％(W/V)的黄原酸胶。该专利声称如果黄原酸胶的浓度约为自0.02至约1.0％(W/V)时该组合物适用于眼用“滴注”。相反地，当黄原酸胶的浓度在1.0％～2.5％(W/V)时，“可获得一种凝胶状的粘度”。因此，该专利公开的组合物被如此组方，使得该组合物在滴入眼睛前既可为非凝胶状的液体亦可为凝胶。该专利并未描述任何可以液体形式施用并在与眼睛接触时胶凝的含黄原酸胶的组合物。根据该专利，任何眼药均可被加入到含有黄原酸胶的组合物中，但该专利列出合适的抗菌药时并未包括氟喹诺酮抗生素。(见Col.3,54-58行)。
WO 99/51273公开了含有黄原酸胶的凝胶型组合物，其中黄原酸胶中起始粘和醋酸酯的含量为至少约4％，起始粘和丙酮酸酯的含量为至少约2.5％。此处引用了WO 99/51273中的全部内容作为参考。
环丙沙星是一种公知的用于药物组合物中的抗生素。由于溶解度的限制，含0.3％(W/W)环丙沙星的、可局部施用的水性组合物通常在较低的pH值(例如pH为4.5)时组方以避免环丙沙星从组合物中析出。美国专利No.5,679,336公开了可局部施用的药物组合物，它是利用聚苯乙烯磺酸于生理pH或近于生理pH时配成的溶液。
将0.3％(W/W)的环丙沙星加入到含有黄原酸胶的单一水样组合物中，即便在pH为4.5时，也会引起环丙沙星和黄原酸胶间沉淀的形成。
发明概述
本发明涉及一种使氟喹诺酮抗生素和黄原酸胶在水性的药物组合物中配伍的方法。根据本发明，将足量钙盐加入该组合物以使氟喹诺酮药物与黄原酸胶相配伍。本发明还涉及组合物，该组合物包括一种氟喹诺酮药物、黄原酸胶和足量的能使氟喹诺酮药物与黄原酸胶配伍的钙盐。本发明的方法和组合物包括最低为0.15重量％的钙盐以使组方在室温时的浊度≤40NTU(浊度单位)。
除其他因素外，本发明基于一个发现，即：不同于一价阳离子或多价阴离子的盐，钙盐在使环丙沙星与黄原酸胶在药物组合物中相配伍时特别有效。
发明详述
除非另外说明，所有成分的浓度都指重量百分比％(W/W)。
众所周知黄原酸胶是一种来源广泛的市售的多糖。本发明的组合物中黄原酸胶的用量是由所需终组合物的性质以及组合物中其它组分的特性和浓度所决定的，但其范围一般在约0.4％到0.8％左右，优选0.5-0.7％。
通常可得到至少两个等级的市售的黄原酸胶，一个为食用或工业级，另一个为药用级。为使最终的药用产物具有增加的澄明度，适宜对即便是药用级原料抛光过滤。本领域熟练技术人员均知道用于抛光过滤的合适的过滤器的尺寸是由需自原材料中除去的杂质的大小决定的。例如：在一个溶液组合物实例中，已经发现由Rhone-Poulenc公司提供的RhodigelClear级的黄原酸胶需用0.45μm的过滤器以除去细胞残留物和杂质。多级过滤器可用来增加抛光过滤过程的总效率。
尽管本发明的组合物中所含氟喹诺酮药的量可以为任意有效治疗量，且取决于许多因素如所选药物的特性和效力，药物的总浓度一般应为约1％或更少。优选的氟喹诺酮抗菌素为环丙沙星。在局部施用眼药组合物剂量中，优选的环丙沙星浓度在0.2-0.4％之间。
除了黄原酸胶和一种氟喹诺酮抗菌药外，本发明的组合物包括一种足量的水溶性的钙盐以使黄原酸胶和氟喹诺酮药物相配伍。钙盐的需用量是由黄原酸胶的浓度、氟喹诺酮药的特性和浓度以及终组方所需的澄明度来决定的。然而，一般而言钙盐的的浓度在室温下应足以使终组方的浊度(nepheols)≤40NTU。适宜的钙盐浓度应≥0.15％。优选的水溶性钙盐包括氯化钙、乳酸钙、醋酸钙、丙酸钙和抗坏血酸钙。最优选的钙盐是氯化钙。
本发明的组合物可包括其他组分。例如：该组合物可包括一种第二活性组分(不限于抗感染药物)。该组合物还可包括一种或多种赋形剂如：药用缓冲剂、防腐剂(包括防腐助剂)、张力调节剂如含一价阳离子的盐、表面活性剂、助溶剂、稳定剂、舒适增强剂(comfort-enhancing agent)、润滑剂、pH调节剂和/或润滑剂，但不局限于此。
下面的实施例用于说明本发明的更多方面，但它们并不从任一方面构成对本发明范围的限定。
实施例
下面的表1-3中所示的每一组方依下述方法制备。如果存在，将溴化苄基十二烷基二甲铵(BDAB)，乙酸、醋酸钠和乙二胺四乙酸二钠用纯净水组合，然后是所列出的盐，其次，如果存在的话，是环丙沙星。所有组分均被搅拌以使之溶解，如果需要，调节其pH。加入黄原酸胶原液并对所得组方搅拌使混合以得到均匀的组合物。如果需要，再次调节其pH值。所获组方在121℃高压灭菌30分钟(使用液体循环)。将经过灭菌的组方冷至室温后装入试管。
使用Brookfield Rheometer测定特定样品在1.2S-1、6S-1，有些实例中为120S-1时的粘度。记录每一样品的目测外观或浊度。使用DRT-100B浊度计(H.F.Scientific)在室温下测定浊度(NTU)。所得结果紧接于表1-3中每一组方的成分下。
实施例1：一价阳离子
表1
| 成份 | ％(W/W) | |||||||
| A | B | C | D | E | F | G | H | |
| 环丙沙星盐酸盐一水合物 | 0.35 | 0.35 | 0.35 | 0.35 | 0.35 | 0.35 | 0.35 | 0.35 |
| 黄原酸胶 | 0.6 | 0.6 | 0.6 | 0.6 | 0.6 | 0.3 | 0.3 | 0.6 |
| 甘露糖醇 | 0 | 0 | 0 | 0 | 4.6 | 4.6 | 0 | 0 |
| 氯化钾 | 1.1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 氯化钠 | 0 | 0.86 | 0.86 | 0.66 | 0 | 0 | 0.86 | 0.86 |
| 二水合氯化钙 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 硼酸 | 0 | 0 | 0 | 0.4 | 0 | 0 | 0 | 0 |
| 聚山梨酯80 | 0 | 0 | 0.05 | 0 | 0 | 0 | 0 | 0 |
| 乙二胺四乙酸二钠 | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 |
| 乙酸 | 0.04 | 0.04 | 0.04 | 0.04 | 0.04 | 0.04 | 0.04 | 0.04 |
| 醋酸钠 | 0.03 | 0.03 | 0.03 | 0.03 | 0.03 | 0.03 | 0.03 | 0.03 |
| 溴化苄基十二烷基二甲铵 | 0.012 | 0.012 | 0.012 | 0.012 | 0.012 | 0.012 | 0.012 | 0.012 |
| 氢氧化钠/盐酸 | pH4.5 | pH4.5 | pH4.5 | pH4.5 | pH4.5 | pH4.5 | pH4.5 | pH4.5 |
| 纯净水 | qs | qs | qs | qs | qs | qs | qs | qs |
| 浊度(NTU)粘度(1.2S-1)粘度(6S-1) | 68 | 67 | 49 | 74 | 248 | 793 | 36 | 70 |
| 3300 | 3100 | -- | 3100 | 凝胶 | 200 | 280 | 3030 | |
| 1040 | 1000 | -- | 980 | 结块 | 45 | 170 | 980 | |
实施例2：多价阴离子
表2
| 成份 | ％(W/W) | ||||
| I | J | K | L | M | |
| 环丙沙星盐酸盐一水合物 | 0.35 | 0.35 | 0 | 0.35 | 0 |
| 黄原酸胶 | 0.6 | 0.6 | 0.6 | 0.3 | 0.3 |
| 硫酸钠 | 1.5 | 1.5 | 1.5 | 1.5 | 1.5 |
| 乙二胺四乙酸二钠 | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 |
| 聚山梨酯80 | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 |
| 溴化苄基十二烷基二甲铵 | 0.012 | 0.012 | 0.012 | 0.012 | 0.012 |
| 氢氧化钠/盐酸 | pH4.5 | pH4.5 | pH4.5 | pH4.5 | pH4.5 |
| 纯净水 | qs | qs | qs | qs | qs |
| 外观 | 几乎澄清 | 沉淀 | 澄清 | 澄清 | 澄清 |
| 粘度(1.2S-1) | 2700 | -- | 4700 | 640 | 690 |
| 粘度(6S-1) | 830 | -- | 1300 | 280 | 300 |
| 粘度(120S-1) | 76 | -- | 106 | 37 | 38 |
在组方I、J和L中，每一组方在放置一周后均观察到有小颗粒出现。
实施例3：多价阳离子
表3
| 成份 | ％(W/W) | ||||
| N | O | P | Q | R | |
| 环丙沙星盐酸盐一水合物 | 0.35 | 0.35 | 0 | 0.35 | 0 |
| 黄原酸胶 | 0.6 | 0.6 | 0.6 | 0.3 | 0.3 |
| 二水合氯化钙 | 1.2 | 1.2 | 1.2 | 1.2 | 1.2 |
| 乙二胺四乙酸二钠 | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 |
| 聚山梨酯80 | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 |
| 溴化苄基十二烷基二甲铵 | 0.012 | 0.012 | 0.012 | 0.012 | 0.012 |
| 氢氧化钠/盐酸 | pH4.5 | PH6.6 | pH4.5 | pH4.5 | pH4.5 |
| 纯净水 | qs | qs | qs | qs | qs |
| 外观 | 澄清 | 模糊 | 澄清 | 澄清 | 澄清 |
| 粘度(1.2S-1) | 4800 | 5300 | 4800 | 1130 | 1340 |
| 粘度(6S-1) | 1230 | 1350 | 1230 | 370 | 390 |
| 粘度(120S-1) | 95 | 103 | 95 | 37 | 38 |
表3(续表)
| 成份 | ％(W/W) | |||||||
| S | T | U | V | W | X | Y | Z | |
| 环丙沙星盐酸盐一水合物 | 0.35 | 0.35 | 0.35 | 0.35 | 0.35 | 0.35 | 0.35 | 0.35 |
| 黄原酸胶 | 0.6 | 0.6 | 0.6 | 0.6 | 0.6 | 0.6 | 0.6 | 0.6 |
| 氯化纳 | 0 | 0 | 0.45 | 0 | 0.26 | 0 | 0 | 0 |
| 二水合氯化钙 | 1.4 | 1.3 | 0.7 | 1.1 | 0.7 | 1.1 | 0.7 | 1.4 |
| 硼酸 | 0 | 0 | 0 | 0.4 | 0.4 | 0.4 | 0.4 | 0 |
| 聚山梨酯80 | 0 | 0 | 0 | 0 | 0 | 0.05 | 0.05 | 0 |
| 乙二胺四乙酸二钠 | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 |
| 乙酸 | 0.04 | 0.04 | 0.04 | 0.04 | 0.04 | 0.04 | 0.04 | 0.04 |
| 醋酸钠 | 0.03 | 0.03 | 0.03 | 0.03 | 0.03 | 0.03 | 0.03 | 0.03 |
| 溴化苄基十二烷基二甲铵 | 0.012 | 0.012 | 0.012 | 0.012 | 0.012 | 0.012 | 0.012 | 0.012 |
| 氢氧化钠/盐酸 | pH4.5 | pH4.5 | pH4.5 | pH4.5 | pH4.5 | pH4.5 | pH4.5 | pH4.5 |
| 纯净水 | qs | qs | qs | qs | qs | qs | qs | qs |
| 浊度(NTU) | 15 | 7 | 15 | 34 | 30 | 29 | 27 | 20 |
| 粘度(1.2S-1) | 5600 | -- | -- | 6000 | 4000 | -- | -- | 3860 |
| 粘度(6S-1) | 1370 | -- | -- | 1630 | 1140 | -- | -- | 1130 |
表3(续表)
| 成份 | ％(W/W) | |||||
| AA | AB | AC | AD | AE | AF | |
| 环丙沙星盐酸盐一水合物 | 0.35 | 0.35 | 0.35 | 0.35 | 0.35 | 0.35 |
| 黄原酸胶 | 0.6 | 0.6 | 0.6 | 0.6 | 0.6 | 0.6 |
| 氯化纳 | 0.26 | 0.26 | 0.26 | 0.5 | 0.65 | 0.78 |
| 二水合氯化钙 | 0.7 | 0.7 | 0.7 | 0.5 | 0.3 | 0.1 |
| 硼酸 | 0 | 0.4 | 0.4 | 0 | 0 | 0 |
| 聚山梨酯80 | 0 | 0 | 0.05 | 0 | 0 | 0 |
| 乙二胺四乙酸二钠 | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 |
| 乙酸 | 0.04 | 0.04 | 0.04 | 0.04 | 0.04 | 0.04 |
| 醋酸钠 | 0.03 | 0.03 | 0.03 | 0.03 | 0.03 | 0.03 |
| 溴化苄基十二烷基二甲铵 | 0.012 | 0.012 | 0.012 | 0.012 | 0.012 | 0.012 |
| 氢氧化钠/盐酸 | pH4.5 | pH4.5 | pH4.5 | pH4.5 | pH4.5 | pH4.5 |
| 纯净水 | qs | qs | qs | qs | qs | qs |
| 浊度(NTU) | 26 | 33 | 25 | 24 | 27 | 43 |
| 粘度(1.2S-1) | 4200 | 3670 | 4300 | -- | -- | -- |
| 粘度(6S-1) | 1210 | 1070 | 1230 | -- | -- | -- |
组方S、T和U在室温下放置5个月，表3中其它组方在室温下放置至少两周。经过上述时间后表3所示任一组方均未观察到有微粒出现。
本发明已通过某些优选实施方案加以描述；然而，在不违反本发明的精神和基本特征的前提下本发明亦可以其它的具体形式实施。上述实施方案可被看作是对本发明的说明，但并不限制本发明的范围，本发明的范围由所附权利要求书而非上述说明书来阐明。
Claims (11)
1.一种制备含有黄原酸胶和一种氟喹诺酮抗生素的水性药物组合物的方法，该方法包括向该组合物中加入至少0.15％(W/W)水溶性钙盐的步骤，其中该组合物在室温下的浊度(NTU)≤40。
2.权利要求1的方法，其中黄原酸胶的浓度为0.4-0.8％(W/W)。
3.权利要求1的方法，其中氟喹诺酮抗生素的浓度为1％(W/W)或更少。
4.权利要求3的方法，其中氟喹诺酮抗生素为环丙沙星，且氟喹诺酮抗生素的浓度为0.2-0.4％(W/W)。
5.权利要求1的方法，其中钙盐选自氯化钙、乳酸钙、醋酸钙、丙酸钙和抗坏血酸钙。
6.权利要求5的方法，其中钙盐为氯化钙。
7.权利要求5的方法，其中钙盐的浓度为至少0.3％(W/W)。
8.权利要求1的方法，其中该组合物还包括一种一价阳离子的水溶性的盐。
9.一种水性药物组合物，该组合物包括用量为0.4-0.8％(W/W)的黄原酸胶、一种用量为1％(W/W)或更少的氟喹诺酮抗生素和用量≥0.15％的水溶性的钙盐，其中该组合物在室温下的浊度(NTU)≤40。
10.权利要求9的水性药物组合物，其中的氟喹诺酮抗生素为环丙沙星，且氟喹诺酮抗生素的含量为0.2-0.4％(W/W)。
11.权利要求10的水性药物组合物，其中该组合物还包括一种一价阳离子的水溶性的盐。
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Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050009922A1 (en) * | 2001-01-27 | 2005-01-13 | Carlson Paul E. | Stable aqueous antimicrobial suspension |
| AU2002331720B2 (en) * | 2001-08-24 | 2007-10-11 | Johns Hopkins University | Proaerolysin containing protease activation sequences and methods of use for treatment of prostate cancer |
| CN1293880C (zh) * | 2002-07-31 | 2007-01-10 | 千寿制药株式会社 | 水性液体制剂和光稳定的水性液体制剂 |
| US8877168B1 (en) | 2002-07-31 | 2014-11-04 | Senju Pharmaceuticals Co., Ltd. | Aqueous liquid preparations and light-stabilized aqueous liquid preparations |
| PT1901749T (pt) * | 2005-05-18 | 2016-11-04 | Raptor Pharmaceuticals Inc | Fluoroquinolonas aerossolizadas e suas utilizações |
| US8546423B2 (en) | 2005-05-18 | 2013-10-01 | Mpex Pharmaceuticals, Inc. | Aerosolized fluoroquinolones and uses thereof |
| CN101547695B (zh) * | 2006-10-12 | 2011-04-27 | 杏林制药株式会社 | 具有改进的加替沙星眼内渗透性的含水液体制剂 |
| MX2010010686A (es) * | 2008-03-31 | 2011-02-23 | Kyorin Seiyaku Kk | Preparacion liquida acuosa que contiene gatifloxacina, su produccion y metodo para suprimir la formacion de precipitado durante el almacenamiento a temperatura mas baja y en el momento del congelamiento y descongelamiento de la preparacion liquida ac |
| BRPI0909366A2 (pt) * | 2008-03-31 | 2017-06-13 | Kyorin Seiyaku Kk | preparação líquida aquosa contendo gatifloxacina |
| TWI495469B (zh) | 2008-06-09 | 2015-08-11 | Alcon Res Ltd | 含有氟喹諾酮抗生素藥物之經改良藥學組成物 |
| HUE050147T2 (hu) | 2008-10-07 | 2020-11-30 | Horizon Orphan Llc | Tüdõgyulladás csökkentése levofloxacin belélegzése útján |
| MX345158B (es) | 2008-10-07 | 2017-01-18 | Raptor Pharmaceuticals Inc | Formulaciones de fluoroquinolona en aerosol para farmacocinetica mejorada. |
| AU2010289326B2 (en) | 2009-09-04 | 2015-09-24 | Horizon Therapeutics U.S. Holding Llc | Use of aerosolized levofloxacin for treating cystic fibrosis |
| WO2011105431A1 (ja) * | 2010-02-24 | 2011-09-01 | 森永乳業株式会社 | 昆布抽出物を有効成分とする抗菌補助剤、抗菌組成物、及び飲食品 |
| US9050357B2 (en) * | 2010-03-08 | 2015-06-09 | Cp Kelco U.S., Inc. | Compositions and methods for producing consumables for patients with dysphagia |
| GR1008168B (el) | 2013-03-14 | 2014-04-08 | "Φαρματεν Α.Β.Ε.Ε.", | Παρεντερικο σκευασμα αντιβακτηριακου παραγοντα φθοριοκινολονης και μεθοδος για την παρασκευη αυτου |
| JP6602534B2 (ja) * | 2013-09-27 | 2019-11-06 | 三栄源エフ・エフ・アイ株式会社 | 液状とろみ剤 |
| JP6538322B2 (ja) * | 2013-09-27 | 2019-07-03 | 三栄源エフ・エフ・アイ株式会社 | 液状とろみ剤 |
| JP6713728B2 (ja) * | 2015-05-01 | 2020-06-24 | 三栄源エフ・エフ・アイ株式会社 | 液状増粘剤 |
| MX2020000265A (es) | 2017-07-07 | 2020-07-22 | Epicentrx Inc | Composiciones para la administración parenteral de agentes terapéuticos. |
| US11298315B2 (en) | 2020-08-26 | 2022-04-12 | Somerset Therapeutics, Llc. | Triamcinolone and moxifloxacin compositions |
| US11484538B2 (en) | 2020-08-26 | 2022-11-01 | Somerset Therapeutics, Llc | Bromfenac, prednisolone, and moxifloxacin compositions and methods |
| US11382910B2 (en) | 2020-08-26 | 2022-07-12 | Somerset Therapeutics, Llc. | Loteprednol and moxifloxacin compositions and methods |
Family Cites Families (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3700451A (en) | 1970-04-06 | 1972-10-24 | Itek Corp | Gelable and gelled compositions |
| US3944427A (en) | 1970-04-06 | 1976-03-16 | Itek Corporation | Gelable and gelled compositions |
| US3784712A (en) | 1970-12-23 | 1974-01-08 | Gen Foods Corp | Gum gelling system xanthan-tara dessert gel |
| CA1070629A (en) | 1975-11-10 | 1980-01-29 | Allen I. Laskin | Process for modifying biopolymers |
| US4135979A (en) | 1976-08-24 | 1979-01-23 | Merck & Co., Inc. | Treatment of xanthan gum to improve clarity |
| US4136177A (en) | 1977-01-31 | 1979-01-23 | American Home Products Corp. | Xanthan gum therapeutic compositions |
| US4136178A (en) | 1977-01-31 | 1979-01-23 | American Home Products Corp. | Locust bean gum therapeutic compositions |
| US4136173A (en) | 1977-01-31 | 1979-01-23 | American Home Products Corp. | Mixed xanthan gum and locust beam gum therapeutic compositions |
| GB8318403D0 (en) | 1983-07-07 | 1983-08-10 | Sutherland I W | Gel-forming polysaccharides |
| FR2551087B1 (fr) | 1983-08-30 | 1986-03-21 | Rhone Poulenc Spec Chim | Procede de traitement d'une solution de polysaccharide et son utilisation |
| DE3335593A1 (de) | 1983-09-30 | 1985-04-11 | Diamalt AG, 8000 München | Gelier- und verdickungsmittel auf der basis von cassia-galactomannanen |
| US4717713A (en) | 1983-10-31 | 1988-01-05 | Research Corporation | Controlled release liquid pharmaceutical |
| US4708861A (en) | 1984-02-15 | 1987-11-24 | The Liposome Company, Inc. | Liposome-gel compositions |
| FR2588189B1 (fr) | 1985-10-03 | 1988-12-02 | Merck Sharp & Dohme | Composition pharmaceutique de type a transition de phase liquide-gel |
| US4647470A (en) | 1985-11-27 | 1987-03-03 | Merck & Co., Inc. | Low-acetyl gellan gum blends |
| FR2618333B1 (fr) | 1987-07-20 | 1990-07-13 | Merck Sharp & Dohme | Composition pharmaceutique et/ou cosmetique a usage topique contenant de la gomme rhamsam |
| US5192535A (en) | 1988-02-08 | 1993-03-09 | Insite Vision Incorporated | Ophthalmic suspensions |
| US4814160A (en) | 1988-03-01 | 1989-03-21 | Colgate-Palmolive Company | Non-bleeding striped dentifrice |
| US5234957A (en) | 1991-02-27 | 1993-08-10 | Noven Pharmaceuticals, Inc. | Compositions and methods for topical administration of pharmaceutically active agents |
| US5446070A (en) | 1991-02-27 | 1995-08-29 | Nover Pharmaceuticals, Inc. | Compositions and methods for topical administration of pharmaceutically active agents |
| DE3843416A1 (de) | 1988-12-23 | 1990-06-28 | Wolff Walsrode Ag | Xanthan mit verbesserter loeslichkeit und verfahren zur herstellung |
| CA2021414C (en) | 1989-07-25 | 2004-09-28 | Daniel H. Doherty | Genetic control of acetylation and pyruvylation of xanthan gum |
| US5461081A (en) | 1989-09-28 | 1995-10-24 | Alcon Laboratories, Inc. | Topical ophthalmic pharmaceutical vehicles |
| FR2653021A1 (fr) | 1989-10-17 | 1991-04-19 | Merck Sharp & Dohme | Composition ophtalmique aqueuse liquide a transition de phase liquide-gel. |
| JP2594486B2 (ja) | 1991-01-15 | 1997-03-26 | アルコン ラボラトリーズ インコーポレイテッド | 局所的眼薬組成物 |
| US5212162A (en) | 1991-03-27 | 1993-05-18 | Alcon Laboratories, Inc. | Use of combinations gelling polysaccharides and finely divided drug carrier substrates in topical ophthalmic compositions |
| ATE162081T1 (de) | 1991-09-17 | 1998-01-15 | Alcon Lab Inc | Chinolan-antibiotika und polystyrolsulfonat enthaltende zusammensetzungen |
| US5192802A (en) | 1991-09-25 | 1993-03-09 | Mcneil-Ppc, Inc. | Bioadhesive pharmaceutical carrier |
| US5318780A (en) | 1991-10-30 | 1994-06-07 | Mediventures Inc. | Medical uses of in situ formed gels |
| US5473062A (en) | 1992-10-29 | 1995-12-05 | Takeda Chemical Industries, Ltd. | Process for producing purified xanthan gum |
| JP3228315B2 (ja) | 1993-04-23 | 2001-11-12 | 信越化学工業株式会社 | キサンタンガムの汚染生菌数を減少させる方法 |
| ES2068762B1 (es) * | 1993-07-21 | 1995-12-01 | Lipotec Sa | Un nuevo preparado farmaceutico para mejorar la biodisponibilidad de drogas de dificil absorcion y procedimiento para su obtencion. |
| EP0757555A4 (en) | 1994-01-14 | 1999-04-07 | Lee Shahinian Jr | METHOD FOR LONG-LASTING AND EXTENDED CORNEAL ANALGESIA |
| US5422116A (en) | 1994-02-18 | 1995-06-06 | Ciba-Geigy Corporation | Liquid ophthalmic sustained release delivery system |
| KR100374098B1 (ko) | 1994-04-08 | 2003-06-09 | 아트릭스 라보라토리스, 인코포레이션 | 조절된방출이식편형성에적합한액체전달조성물 |
| US5523301A (en) | 1994-08-05 | 1996-06-04 | Merck & Co., Inc. | Optic nerve health |
| ATE208186T1 (de) | 1994-08-30 | 2001-11-15 | Alcon Lab Inc | Thermisch gelierende trägerstoffe zur arzneistoffabgabe, die zelluloseether enthalten |
| US5972326A (en) | 1995-04-18 | 1999-10-26 | Galin; Miles A. | Controlled release of pharmaceuticals in the anterior chamber of the eye |
| FR2742336B1 (fr) | 1995-12-19 | 1998-03-06 | Chauvin Lab Sa | Collyre destine notamment au traitement de l'oeil sec |
| SE9603480L (sv) | 1996-09-23 | 1998-03-24 | Johan Carlfors | Beredningsform för svårlösliga läkemedel |
| FR2754712B1 (fr) | 1996-10-17 | 1999-09-03 | Merck Sharp Dohme Chibret Lab | Compositions ophtalmiques |
| US5888493A (en) | 1996-12-05 | 1999-03-30 | Sawaya; Assad S. | Ophthalmic aqueous gel formulation and related methods |
| JP2002501533A (ja) | 1997-05-30 | 2002-01-15 | メルク エンド カンパニー インコーポレーテッド | 高眼圧症治療のための眼科用組成物 |
| AU740874B2 (en) | 1997-06-26 | 2001-11-15 | Merck & Co., Inc. | Method for optimizing retinal and optic nerve health |
| BR9811789A (pt) * | 1997-09-12 | 2000-09-05 | Procter & Gamble | Artigo de limpeza e condicionamento para tratamento pessoal de utilização única, descartável e processos para manufaturar esse artigo e para limpar e condicionar a pele ou cabelo com esse artigo |
| ES2203103T3 (es) | 1998-04-07 | 2004-04-01 | Alcon Manufacturing Ltd. | Composiciones oftalmicas gelificantes que contienen goma xantana. |
| US6166012A (en) * | 1999-07-30 | 2000-12-26 | Allergan Sales, Inc. | Antibiotic compositions and method for using same |
-
2000
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- 2000-10-10 KR KR1020027004809A patent/KR20020048967A/ko not_active Application Discontinuation
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- 2000-10-10 DE DE60003445T patent/DE60003445T2/de not_active Expired - Lifetime
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| Publication number | Publication date |
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| TR200201174T2 (tr) | 2002-08-21 |
| KR20020048967A (ko) | 2002-06-24 |
| MXPA02004349A (es) | 2003-09-22 |
| ATE243038T1 (de) | 2003-07-15 |
| EP1225898B1 (en) | 2003-06-18 |
| DK1225898T3 (da) | 2003-09-15 |
| HK1045940A1 (zh) | 2002-12-20 |
| JP2003513046A (ja) | 2003-04-08 |
| CA2386822A1 (en) | 2001-05-10 |
| BR0015256A (pt) | 2002-06-18 |
| WO2001032181A2 (en) | 2001-05-10 |
| PT1225898E (pt) | 2003-10-31 |
| PL354928A1 (en) | 2004-03-22 |
| AR026227A1 (es) | 2003-01-29 |
| EP1225898A2 (en) | 2002-07-31 |
| DE60003445D1 (de) | 2003-07-24 |
| US6331540B1 (en) | 2001-12-18 |
| ES2199873T3 (es) | 2004-03-01 |
| DE60003445T2 (de) | 2003-12-24 |
| AU8008300A (en) | 2001-05-14 |
| WO2001032181A3 (en) | 2002-05-02 |
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