JP6430935B2 - クロルフェニラミン又はその塩の安定化方法 - Google Patents
クロルフェニラミン又はその塩の安定化方法 Download PDFInfo
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- JP6430935B2 JP6430935B2 JP2015519867A JP2015519867A JP6430935B2 JP 6430935 B2 JP6430935 B2 JP 6430935B2 JP 2015519867 A JP2015519867 A JP 2015519867A JP 2015519867 A JP2015519867 A JP 2015519867A JP 6430935 B2 JP6430935 B2 JP 6430935B2
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- 239000011770 retinyl acetate Substances 0.000 description 1
- 229940108325 retinyl palmitate Drugs 0.000 description 1
- 235000019172 retinyl palmitate Nutrition 0.000 description 1
- 239000011769 retinyl palmitate Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- GQTHJBOWLPZUOI-FJXQXJEOSA-M sodium D-pantothenate Chemical compound [Na+].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O GQTHJBOWLPZUOI-FJXQXJEOSA-M 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- 229940068459 sodium pantothenate Drugs 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- GEYJUFBPCGDENK-UHFFFAOYSA-M sodium;3,8-dimethyl-5-propan-2-ylazulene-1-sulfonate Chemical compound [Na+].CC(C)C1=CC=C(C)C2=C(S([O-])(=O)=O)C=C(C)C2=C1 GEYJUFBPCGDENK-UHFFFAOYSA-M 0.000 description 1
- 239000012453 solvate 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
- 239000000600 sorbitol Substances 0.000 description 1
- 229940063673 spermidine Drugs 0.000 description 1
- 125000002730 succinyl group Chemical group C(CCC(=O)*)(=O)* 0.000 description 1
- 229960004306 sulfadiazine Drugs 0.000 description 1
- SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 description 1
- ZZORFUFYDOWNEF-UHFFFAOYSA-N sulfadimethoxine Chemical compound COC1=NC(OC)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 ZZORFUFYDOWNEF-UHFFFAOYSA-N 0.000 description 1
- 229960000973 sulfadimethoxine Drugs 0.000 description 1
- 229960004257 sulfaguanidine Drugs 0.000 description 1
- BRBKOPJOKNSWSG-UHFFFAOYSA-N sulfaguanidine Chemical compound NC(=N)NS(=O)(=O)C1=CC=C(N)C=C1 BRBKOPJOKNSWSG-UHFFFAOYSA-N 0.000 description 1
- 229960004818 sulfaphenazole Drugs 0.000 description 1
- QWCJHSGMANYXCW-UHFFFAOYSA-N sulfaphenazole Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=CC=NN1C1=CC=CC=C1 QWCJHSGMANYXCW-UHFFFAOYSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229940104261 taurate Drugs 0.000 description 1
- 229960000337 tetryzoline 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
- 229940033663 thimerosal Drugs 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- NZHGWWWHIYHZNX-CSKARUKUSA-N tranilast Chemical compound C1=C(OC)C(OC)=CC=C1\C=C\C(=O)NC1=CC=CC=C1C(O)=O NZHGWWWHIYHZNX-CSKARUKUSA-N 0.000 description 1
- 229960005342 tranilast Drugs 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 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
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 229960001939 zinc chloride Drugs 0.000 description 1
- 239000011576 zinc lactate Substances 0.000 description 1
- 229940050168 zinc lactate Drugs 0.000 description 1
- 235000000193 zinc lactate Nutrition 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- 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
-
- A—HUMAN NECESSITIES
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
- B65D47/00—Closures with filling and discharging, or with discharging, devices
- B65D47/04—Closures with discharging devices other than pumps
- B65D47/06—Closures with discharging devices other than pumps with pouring spouts or tubes; with discharge nozzles or passages
- B65D47/18—Closures with discharging devices other than pumps with pouring spouts or tubes; with discharge nozzles or passages for discharging drops; Droppers
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Ophthalmology & Optometry (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Mechanical Engineering (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
項1. クロルフェニラミン及び/又はその薬学的に許容される塩を含有し、pHが7.0以上である液剤が、容器に収容されてなるクロルフェニラミン類含有製品であって、
前記容器が、前記液剤を収容する容器本体と、前記容器本体に収容された液剤を注出する注出口を有する注出部と、前記注出口をふさぐ蓋部とを備え、
前記注出部の内部空間の壁面、及び前記蓋部において前記注出口と対向する壁面の少なくとも一方が、ポリブチレンテレフタレートを含む樹脂で構成されていることを特徴とする、
クロルフェニラミン類含有製品。
項2. 前記注出部が、前記液剤を液滴状で注出するノズルであり、当該ノズルの内部空間の壁面がポリブチレンテレフタレートを含む樹脂で構成されている、項1に記載のクロルフェニラミン類含有製品。
項3. 前記容器本体が、ポリエチレンテレフタレートを含む樹脂で構成されている、項1又は2に記載のクロルフェニラミン類含有製品。
項4. 前記液剤のpHが7.5〜9.0である、項1〜3のいずれかに記載のクロルフェニラミン類含有製品。
項5. 前記液剤に、クロルフェニラミン及び/又はその薬学的に許容される塩が0.0006〜0.2w/v%含まれる、項1〜4のいずれかに記載のクロルフェニラミン類含有製品。
項6. 前記液剤が点眼剤である、項1〜5のいずれかに記載のクロルフェニラミン類含有製品。
項7. クロルフェニラミン及び/又はその薬学的に許容される塩を含有し、pHが7.0以上である液剤の安定化方法であって、
容器の内壁を構成する領域の少なくとも一部分が、ポリブチレンテレフタレートを含む樹脂によって構成されている容器に、クロルフェニラミン及び/又はその薬学的に許容される塩を含有する液剤を収容することを特徴とする、
安定化方法。
項8. 前記容器が、前記液剤を収容する容器本体と、前記容器本体に収容された液剤を注出する注出口を有する注出部と、前記注出口をふさぐ蓋部とを備え、
前記注出部の内部空間の壁面、及び前記蓋部において前記注出口と対向する壁面の少なくとも一方が、ポリブチレンテレフタレートを含む樹脂で構成されている、項7に記載の安定化方法。
項9. 前記注出部が、前記液剤を液滴状で注出するノズルであり、当該ノズルの内部空間の壁面がポリブチレンテレフタレートを含む樹脂で構成されている、項7又は8に記載の安定化方法。
項10. 前記容器本体が、ポリエチレンテレフタレートを含む樹脂で構成されている、項7〜9のいずれかに記載の安定化方法。
項11. 前記液剤のpHが7.5〜9.0である、項7〜10のいずれかに記載の安定化方法。
項12. 前記液剤に、クロルフェニラミン及び/又はその薬学的に許容される塩が0.0006〜0.2w/v%含まれる、項7〜11のいずれかに記載の安定化方法。
項13. 前記液剤が点眼剤である、項7〜12のいずれかに記載の安定化方法。
本発明のクロルフェニラミン類含有製品は、クロルフェニラミン及び/又はその塩を含有し、pHが7.0以上である液剤が、注出部の内部空間の壁面及び/又は蓋部において注出部の注出口と対向する壁面がポリブチレンテレフタレートで構成された容器に収容されていることを特徴とする。以下、本発明のクロルフェニラミン類含有製品について、詳述する。
本発明のクロルフェニラミン類含有製品において、容器に収容する液剤は、クロルフェニラミン及び/又はその塩を含有する。クロルフェニラミンは、3−(4−クロロフェニル)−N,N−ジメチル−3−ピリジン−2−イル−プロパン−1−アミンとも称され、抗ヒスタミン剤として公知の化合物である。
本発明のクロルフェニラミン類含有製品では、前記液剤を収容するために、容器本体と注出部と蓋部とを備え、前記注出部の内部空間の壁面及び/又は蓋部において注出部の注出口と対向する壁面がポリブチレンテレフタレートを含む樹脂で構成されている容器が使用される。
前記容器を構成する容器本体とは、前記液剤を収容する部位である。当該容器本体の形状、大きさについては、特に制限されず、収容する液剤の種類に応じて適宜設定される。
前記容器は、前記注出部の内部空間の壁面、及び前記蓋部において前記注出口と対向する壁面の少なくとも一方が、ポリブチレンテレフタレート(PBT)を含む樹脂によって構成される。ここで、「蓋部において前記注出口と対向する壁面」とは、蓋部を容器本体及び/又は注出部に取りつけた際に注出口を覆う蓋部の内壁部分に該当する。具体的には、図2、5、及び6を例に挙げると、符号5で示した面部分が「注出部の内部空間の壁面」に該当し、符号6で示した面部分が「蓋部において前記注出口と対向する壁面」に相当する。
本発明の安定化方法は、クロルフェニラミン及び/又はその薬学的に許容される塩を含有し、pHが7.0以上である液剤の安定化方法であり、当該液剤を、容器の内壁を構成する領域の少なくとも一部分がポリブチレンテレフタレートを含む樹脂で構成された容器に収容することを特徴とするものである。
表2及び3に示す液剤を調製して各種容器に収容して保存した際のクロルフェニラミンマレイン酸塩の含有量の経時変化を測定した。具体的には、表2及び3に示す液剤を常法に従って調製して、表1に示す各容器に収容し、密封状態にして50℃の温度条件にて8週間静置することにより保存した。その際、容器1及び3の場合には液剤の収容量は10mLにし、容器2の場合には液剤の収容量は5mLにした。また、容器1及び3の場合には、保存中は、蓋部分が下面、容器本体の底部が上面となるように、容器を倒立させた状態で静置した。保存開始前、保存開始から2週間後及び8週間後に、容器中の液剤をサンプリングし、液剤中のクロルフェニラミンマレイン酸塩の含有量をHPLCにて測定することにより、保存後のクロルフェニラミンマレイン酸塩の残存率(%)を算出した。なお、容器3は従来汎用されている点眼容器の例である。また、ガラスは一般に薬物の吸着が認められないことが知られており、容器2はクロルフェニラミンマレイン酸塩が吸着し難い容器の例である。
表4及び5に示す液剤を常法に従って調製し、前記試験例1と同様の方法で、表1に示す各容器に収容して保存した際のクロルフェニラミンマレイン酸塩の残存率を測定した。なお、本試験では、50℃での保存期間は4週間に設定した。
表6に示す液剤を常法に従って調製し、前記試験例1と同様の方法で、表1に示す各容器に収容して保存した際のクロルフェニラミンマレイン酸塩の残存率を測定した。なお、本試験では、50℃での保存期間は4週間に設定した。
表7に示す液剤を常法に従って調製し、前記試験例1と同様の方法で、表1に示す各容器に収容して保存し、各薬理成分(ジブカイン塩酸塩、ナファゾリン塩酸塩、ピリドキシン塩酸塩)の含有量の経時変化をHPLCにより測定し、その残存率を求めた。なお、本試験では、50℃での保存期間は2週間に設定した。
表8に示す液剤を調製し、当該液剤と接液した状態でのポリエチレン又はポリブチレンテレフタレートに対する脂溶性抗酸化剤(ブチルヒドロキシアニソール)の吸着性について評価を行った。具体的には、6mLの液剤を収容したガラス製アンプル容器に、ポリエチレン製ノズル(低密度ポリエチレン樹脂製の点眼容器用のノズル;商品名「ノバテック(登録商標)LD LJ808」、日本ポリエチレン株式会社製)又はポリブチレンテレフタレート製ノズル(点眼容器用のノズル;商品名「ノバデュラン(登録商標) 5010R5X」、三菱エンジニアリングプラスチック株式会社製)1個を入れて、ガラス製アンプル容器の開口部を熔封することにより密封した。液剤中にノズルが浸漬した状態で50℃の温度条件にて2週間静置した。次いで、密封したガラス製アンプル容器を開封し、液剤中の脂溶性抗酸化剤含有量をHPLCにて測定することにより、保存後の脂溶性抗酸化剤の残存率(%)を算出した。また、比較のために、ノズルを入れずに上記と同様の方法で試験を行った。
2 注出部
3 蓋部
4 抽出部の内部空間
5 抽出部の内部空間の壁面
6 蓋部において注出部の注出口と対向する壁面
Claims (13)
- クロルフェニラミン及び/又はその薬学的に許容される塩を含有し、pHが7.0以上である液剤が、容器に収容されてなるクロルフェニラミン類含有製品であって、
前記容器が、前記液剤を収容する容器本体と、前記容器本体に収容された液剤を注出する注出口を有する注出部と、前記注出口をふさぐ蓋部とを備え、
前記注出部の内部空間の壁面、及び前記蓋部において前記注出口と対向する壁面の少なくとも一方が、ポリブチレンテレフタレートを含む樹脂で構成されていることを特徴とする、
クロルフェニラミン類含有製品。 - 前記注出部が、前記液剤を液滴状で注出するノズルであり、当該ノズルの内部空間の壁面がポリブチレンテレフタレートを含む樹脂で構成されている、請求項1に記載のクロルフェニラミン類含有製品。
- 前記容器本体が、ポリエチレンテレフタレートを含む樹脂で構成されている、請求項1又は2に記載のクロルフェニラミン類含有製品。
- 前記液剤のpHが7.5〜9.0である、請求項1〜3のいずれかに記載のクロルフェニラミン類含有製品。
- 前記液剤に、クロルフェニラミン及び/又はその薬学的に許容される塩が0.0006〜0.2w/v%含まれる、請求項1〜4のいずれかに記載のクロルフェニラミン類含有製品。
- 前記液剤が点眼剤である、請求項1〜5のいずれかに記載のクロルフェニラミン類含有製品。
- クロルフェニラミン及び/又はその薬学的に許容される塩を含有し、pHが7.0以上である液剤の安定化方法であって、
容器の内壁を構成する領域の少なくとも一部分が、ポリブチレンテレフタレートを含む樹脂によって構成されている容器に、クロルフェニラミン及び/又はその薬学的に許容される塩を含有する液剤を収容することを特徴とする、
安定化方法。 - 前記容器が、前記液剤を収容する容器本体と、前記容器本体に収容された液剤を注出する注出口を有する注出部と、前記注出口をふさぐ蓋部とを備え、
前記注出部の内部空間の壁面、及び前記蓋部において前記注出口と対向する壁面の少なくとも一方が、ポリブチレンテレフタレートを含む樹脂で構成されている、請求項7に記載の安定化方法。 - 前記注出部が、前記液剤を液滴状で注出するノズルであり、当該ノズルの内部空間の壁面がポリブチレンテレフタレートを含む樹脂で構成されている、請求項7又は8に記載の安定化方法。
- 前記容器本体が、ポリエチレンテレフタレートを含む樹脂で構成されている、請求項7〜9のいずれかに記載の安定化方法。
- 前記液剤のpHが7.5〜9.0である、請求項7〜10のいずれかに記載の安定化方法。
- 前記液剤に、クロルフェニラミン及び/又はその薬学的に許容される塩が0.0006〜0.2w/v%含まれる、請求項7〜11のいずれかに記載の安定化方法。
- 前記液剤が点眼剤である、請求項7〜12のいずれかに記載の安定化方法。
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