JP2016108260A - 眼科用液剤 - Google Patents
眼科用液剤 Download PDFInfo
- Publication number
- JP2016108260A JP2016108260A JP2014245659A JP2014245659A JP2016108260A JP 2016108260 A JP2016108260 A JP 2016108260A JP 2014245659 A JP2014245659 A JP 2014245659A JP 2014245659 A JP2014245659 A JP 2014245659A JP 2016108260 A JP2016108260 A JP 2016108260A
- Authority
- JP
- Japan
- Prior art keywords
- hydrogen peroxide
- concentration
- stabilizer
- ophthalmic solution
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000002997 ophthalmic solution Substances 0.000 title claims abstract description 39
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims abstract description 280
- 239000003381 stabilizer Substances 0.000 claims abstract description 46
- 229940054534 ophthalmic solution Drugs 0.000 claims abstract description 32
- 239000000243 solution Substances 0.000 claims abstract description 31
- 150000003839 salts Chemical class 0.000 claims description 11
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 claims description 8
- 229920001287 Chondroitin sulfate Polymers 0.000 claims description 8
- KXKPYJOVDUMHGS-OSRGNVMNSA-N chondroitin sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](OS(O)(=O)=O)[C@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](C(O)=O)O1 KXKPYJOVDUMHGS-OSRGNVMNSA-N 0.000 claims description 8
- 229940059329 chondroitin sulfate Drugs 0.000 claims description 8
- 150000004677 hydrates Chemical class 0.000 claims description 8
- DUYCTCQXNHFCSJ-UHFFFAOYSA-N dtpmp Chemical group OP(=O)(O)CN(CP(O)(O)=O)CCN(CP(O)(=O)O)CCN(CP(O)(O)=O)CP(O)(O)=O DUYCTCQXNHFCSJ-UHFFFAOYSA-N 0.000 claims description 7
- 229960001922 sodium perborate Drugs 0.000 claims description 7
- YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 claims description 7
- 239000007788 liquid Substances 0.000 abstract description 40
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- 230000000694 effects Effects 0.000 description 18
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
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- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
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- 235000010339 sodium tetraborate Nutrition 0.000 description 3
- XSVSPKKXQGNHMD-UHFFFAOYSA-N 5-bromo-3-methyl-1,2-thiazole Chemical compound CC=1C=C(Br)SN=1 XSVSPKKXQGNHMD-UHFFFAOYSA-N 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
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- 241000222122 Candida albicans Species 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
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- DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 description 2
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- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
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- 229940095064 tartrate Drugs 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
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Images
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Abstract
Description
0.0045X+0.4712 ≦ Y ≦ 1.2544X+11.9680・・・(1)
(但し、Xは5〜80)
0.0045X+0.4712 ≦ Y ≦ 1.2544X+11.9680・・・(1)
(但し、Xは5〜80)
4NaBO3 + 5H2O → 4H2O2 + Na2B4O7 + 2NaOH
分解生成物である硼酸ナトリウムは眼科用液剤には汎用されており、水酸化ナトリウムは液剤のpHが中性付近に維持される範囲内であれば問題がなく、安全性の高いものであることがわかる。
以下本発明をより具体的に明らかにするために、いくつかの例を示す。
過酸化水素源として過硼酸ナトリウム4水和物、過酸化水素安定化剤としてジエチレントリアミンペンタ(メチレンホスホン酸)(以下「DTPMPA」と略す)を各種の濃度で蒸留水に溶解し本発明の眼科用液剤を調製した。各眼科用液剤には、緩衝剤として無水リン酸一水素ナトリウムを0.1w/v%とリン酸二水素カリウムを0.05w/v%、等張化剤として塩化ナトリウムを0.83w/v%、増粘剤としてコンドロイチン硫酸ナトリウムを0.001w/v%、低分子量ヒアルロン酸を0.001w/v%、になるように添加した。
試験管に各眼科用液剤0.5mLを取り、5%濃度の硫酸チタン(IV)溶液を1.5mL加えて攪拌した。波長407nmにおける吸光度を測定して、検量線から過酸化水素濃度を計算した。
過硼酸ナトリウム4水和物の濃度を調整して、過酸化水素濃度が5、10、15、20、40ppmになるようにし、DTPMPAの濃度を3ppm、その他の成分は実施例1の液剤と同様に設定した眼科用液剤を調製した。この各液剤について、下記の保存効力試験を実施した。
第16改正 日本薬局方・参考情報に記載の保存効力試験に従って試験を実施した。細菌3種(黄色ブドウ球菌:S.a.、緑膿菌:P.a.、大腸菌:E.c.)、真菌1種(カンジダ菌:C.a.)及びカビ1種(黒麹菌:A.b.)を1mLあたり105〜106個になるように加え、23℃に静置した。7、14、21、28日目に菌を接種した溶液を適宜希釈し、それぞれを培養した後、生菌数を測定し、初期菌数からの変化量を対数表示で示した。
菌減少量[対数換算]=LOG(調製直後の菌懸濁液1ml中の生菌数)−LOG(期間経過後の菌懸濁液1ml中の生菌数)
前記試験の結果を対象微生物ごとに表1〜表5に示す。
表6に示すような各処方の液剤を調製した。各液剤2.7mLに2.5w/v%のリゾチーム水溶液を0.3mL加えて、混合後のリゾチームの濃度が0.25w/v%となるようにした。リゾチームを含む各処方の液剤に、レンズ(医薬審第645号に記載されているグループ4に属するレンズ、含水率58%)1枚を入れて35℃のインキュベーター内で20時間静置した。0.9w/v%の塩化ナトリウム水溶液ですすいだ後、蛍光光度計を用いてレンズを測定した(表7の「浸漬後の蛍光強度」)。蛍光光度計の測定条件は、励起光280nm、測定蛍光340nmである。
Claims (6)
- 有効量の過酸化水素源を含み、
液剤中の過酸化水素濃度をXppmとし、過酸化水素安定化剤濃度をYppmとするときXとYが次の関係式(1)を満たす眼科用液剤。
0.0045X+0.4712 ≦ Y ≦ 1.2544X+11.9680・・・(1)
(但し、Xは5〜80) - 過酸化水素源が、過硼酸ナトリウム、その水和物および過酸化水素から選択される一種以上である請求項1に記載の眼科用液剤。
- 過酸化水素安定化剤が、ジエチレントリアミンペンタ(メチレンホスホン酸)である請求項1または2に記載の眼科用液剤。
- 80℃で1週間保存したときの過酸化水素濃度残存率が、80%以上である請求項1乃至3のいずれかに記載の眼科用液剤。
- コンドロイチン硫酸及び/又はその塩をさらに含む請求項1乃至4のいずれかに記載の眼科用液剤。
- コンドロイチン硫酸ナトリウムが0.00001〜10w/v%の濃度である請求項5に記載の眼科用液剤。
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JP2004509925A (ja) * | 2000-09-28 | 2004-04-02 | ノバルティス アクチエンゲゼルシャフト | 安定化過酸化水素溶液 |
JP2011093897A (ja) * | 2009-09-30 | 2011-05-12 | Rohto Pharmaceutical Co Ltd | 眼科用液体組成物 |
JP2011136988A (ja) * | 2009-12-02 | 2011-07-14 | Rohto Pharmaceutical Co Ltd | シリコーンハイドロゲルコンタクトレンズ用眼科組成物 |
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JP2011093897A (ja) * | 2009-09-30 | 2011-05-12 | Rohto Pharmaceutical Co Ltd | 眼科用液体組成物 |
JP2011136988A (ja) * | 2009-12-02 | 2011-07-14 | Rohto Pharmaceutical Co Ltd | シリコーンハイドロゲルコンタクトレンズ用眼科組成物 |
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