JP5879945B2 - Nasal drops - Google Patents
Nasal drops Download PDFInfo
- Publication number
- JP5879945B2 JP5879945B2 JP2011250593A JP2011250593A JP5879945B2 JP 5879945 B2 JP5879945 B2 JP 5879945B2 JP 2011250593 A JP2011250593 A JP 2011250593A JP 2011250593 A JP2011250593 A JP 2011250593A JP 5879945 B2 JP5879945 B2 JP 5879945B2
- Authority
- JP
- Japan
- Prior art keywords
- physiological saline
- nasal
- sodium hydroxide
- appropriate amount
- chlorpheniramine maleate
- 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.)
- Active
Links
- 239000007923 nasal drop Substances 0.000 title claims description 37
- 229940100662 nasal drops Drugs 0.000 title claims description 19
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 claims description 32
- 229940046978 chlorpheniramine maleate Drugs 0.000 claims description 32
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 17
- 229920001223 polyethylene glycol Polymers 0.000 claims description 15
- 239000002202 Polyethylene glycol Substances 0.000 claims description 14
- 235000011187 glycerol Nutrition 0.000 claims description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 102
- 239000002504 physiological saline solution Substances 0.000 description 52
- 239000007922 nasal spray Substances 0.000 description 35
- 229940097496 nasal spray Drugs 0.000 description 35
- 230000007794 irritation Effects 0.000 description 24
- 239000003814 drug Substances 0.000 description 20
- 230000000052 comparative effect Effects 0.000 description 14
- 229940087213 glycerin 2000 mg Drugs 0.000 description 11
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 7
- 229940057838 polyethylene glycol 4000 Drugs 0.000 description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- ZZHLYYDVIOPZBE-UHFFFAOYSA-N Trimeprazine Chemical compound C1=CC=C2N(CC(CN(C)C)C)C3=CC=CC=C3SC2=C1 ZZHLYYDVIOPZBE-UHFFFAOYSA-N 0.000 description 4
- 239000000739 antihistaminic agent Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- -1 methodirazine Chemical compound 0.000 description 4
- 150000005846 sugar alcohols Polymers 0.000 description 4
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 230000007815 allergy Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 210000002850 nasal mucosa Anatomy 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 229960000351 terfenadine Drugs 0.000 description 3
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- CNIIGCLFLJGOGP-UHFFFAOYSA-N 2-(1-naphthalenylmethyl)-4,5-dihydro-1H-imidazole Chemical compound C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 CNIIGCLFLJGOGP-UHFFFAOYSA-N 0.000 description 2
- MBUVEWMHONZEQD-UHFFFAOYSA-N Azeptin Chemical compound C1CN(C)CCCC1N1C(=O)C2=CC=CC=C2C(CC=2C=CC(Cl)=CC=2)=N1 MBUVEWMHONZEQD-UHFFFAOYSA-N 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 2
- HOKDBMAJZXIPGC-UHFFFAOYSA-N Mequitazine Chemical compound C12=CC=CC=C2SC2=CC=CC=C2N1CC1C(CC2)CCN2C1 HOKDBMAJZXIPGC-UHFFFAOYSA-N 0.000 description 2
- 208000003251 Pruritus Diseases 0.000 description 2
- 206010039085 Rhinitis allergic Diseases 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 229960003790 alimemazine Drugs 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 201000010105 allergic rhinitis Diseases 0.000 description 2
- 230000001387 anti-histamine Effects 0.000 description 2
- 229940125715 antihistaminic agent Drugs 0.000 description 2
- GXDALQBWZGODGZ-UHFFFAOYSA-N astemizole Chemical compound C1=CC(OC)=CC=C1CCN1CCC(NC=2N(C3=CC=CC=C3N=2)CC=2C=CC(F)=CC=2)CC1 GXDALQBWZGODGZ-UHFFFAOYSA-N 0.000 description 2
- 229960004574 azelastine Drugs 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 229960000428 carbinoxamine Drugs 0.000 description 2
- OJFSXZCBGQGRNV-UHFFFAOYSA-N carbinoxamine Chemical compound C=1C=CC=NC=1C(OCCN(C)C)C1=CC=C(Cl)C=C1 OJFSXZCBGQGRNV-UHFFFAOYSA-N 0.000 description 2
- 229960003291 chlorphenamine Drugs 0.000 description 2
- SOYKEARSMXGVTM-UHFFFAOYSA-N chlorphenamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 SOYKEARSMXGVTM-UHFFFAOYSA-N 0.000 description 2
- 229960002881 clemastine Drugs 0.000 description 2
- YNNUSGIPVFPVBX-NHCUHLMSSA-N clemastine Chemical compound CN1CCC[C@@H]1CCO[C@@](C)(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 YNNUSGIPVFPVBX-NHCUHLMSSA-N 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 229960000520 diphenhydramine Drugs 0.000 description 2
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 2
- 229960000325 emedastine Drugs 0.000 description 2
- KBUZBQVCBVDWKX-UHFFFAOYSA-N emedastine Chemical compound N=1C2=CC=CC=C2N(CCOCC)C=1N1CCCN(C)CC1 KBUZBQVCBVDWKX-UHFFFAOYSA-N 0.000 description 2
- 229960003449 epinastine Drugs 0.000 description 2
- WHWZLSFABNNENI-UHFFFAOYSA-N epinastine Chemical compound C1C2=CC=CC=C2C2CN=C(N)N2C2=CC=CC=C21 WHWZLSFABNNENI-UHFFFAOYSA-N 0.000 description 2
- 229960005042 mequitazine Drugs 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000000116 mitigating effect Effects 0.000 description 2
- WYWIFABBXFUGLM-UHFFFAOYSA-N oxymetazoline Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C)=C1CC1=NCCN1 WYWIFABBXFUGLM-UHFFFAOYSA-N 0.000 description 2
- 229960003910 promethazine Drugs 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- BYJAVTDNIXVSPW-UHFFFAOYSA-N tetryzoline Chemical compound N1CCN=C1C1C2=CC=CC=C2CCC1 BYJAVTDNIXVSPW-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- FMCGSUUBYTWNDP-ONGXEEELSA-N (1R,2S)-2-(dimethylamino)-1-phenyl-1-propanol Chemical compound CN(C)[C@@H](C)[C@H](O)C1=CC=CC=C1 FMCGSUUBYTWNDP-ONGXEEELSA-N 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 108010000437 Deamino Arginine Vasopressin Proteins 0.000 description 1
- 208000019872 Drug Eruptions Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- FMCGSUUBYTWNDP-UHFFFAOYSA-N N-Methylephedrine Natural products CN(C)C(C)C(O)C1=CC=CC=C1 FMCGSUUBYTWNDP-UHFFFAOYSA-N 0.000 description 1
- 206010028741 Nasal inflammation Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 239000008118 PEG 6000 Substances 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 1
- 208000036071 Rhinorrhea Diseases 0.000 description 1
- 206010039101 Rhinorrhoea Diseases 0.000 description 1
- UFLGIAIHIAPJJC-UHFFFAOYSA-N Tripelennamine Chemical compound C=1C=CC=NC=1N(CCN(C)C)CC1=CC=CC=C1 UFLGIAIHIAPJJC-UHFFFAOYSA-N 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000003212 astringent agent Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 239000002826 coolant Substances 0.000 description 1
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
- 229960004281 desmopressin Drugs 0.000 description 1
- NFLWUMRGJYTJIN-NXBWRCJVSA-N desmopressin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSCCC(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(N)=O)=O)CCC(=O)N)C1=CC=CC=C1 NFLWUMRGJYTJIN-NXBWRCJVSA-N 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 229960002221 methylephedrine Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229960005016 naphazoline Drugs 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- BAINIUMDFURPJM-UHFFFAOYSA-N oxatomide Chemical compound O=C1NC2=CC=CC=C2N1CCCN(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 BAINIUMDFURPJM-UHFFFAOYSA-N 0.000 description 1
- 229960002698 oxatomide Drugs 0.000 description 1
- 229960001528 oxymetazoline Drugs 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
- 229960001802 phenylephrine Drugs 0.000 description 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 206010041232 sneezing Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- KQKPFRSPSRPDEB-UHFFFAOYSA-N sumatriptan Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 KQKPFRSPSRPDEB-UHFFFAOYSA-N 0.000 description 1
- 229960003708 sumatriptan Drugs 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 229960000337 tetryzoline Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 229960003223 tripelennamine Drugs 0.000 description 1
- 229960001128 triprolidine Drugs 0.000 description 1
- CBEQULMOCCWAQT-WOJGMQOQSA-N triprolidine Chemical compound C1=CC(C)=CC=C1C(\C=1N=CC=CC=1)=C/CN1CCCC1 CBEQULMOCCWAQT-WOJGMQOQSA-N 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 230000001457 vasomotor Effects 0.000 description 1
- 208000001319 vasomotor rhinitis Diseases 0.000 description 1
Description
本発明は、点鼻剤の分野に関する。さらに詳しくは、塩基性薬物を含有する点鼻剤において点鼻時に生じる刺激感を緩和する技術である。 The present invention relates to the field of nasal drops. More specifically, it is a technique for alleviating the irritation sensation that occurs during nasal drop in nasal drops containing a basic drug.
薬物の吸収は、一般的に薬物の分子型分率が高いほどよいと言われている(非特許文献1)。塩基性薬物に関しては、pHが高くなるほど分子型分率が高くなることから、pHが高いほど吸収性が増加し、酸性薬物に関しては、pHが低くなるほど分子型分率が高くなることから、pHが低いほど吸収性が増加する。
代表的な塩基性薬物であるクロルフェニラミンマレイン酸塩は抗ヒスタミン薬の一つである。じん麻疹、血管運動性浮腫、枯草熱、皮膚疾患に伴うそう痒( 湿疹、皮膚炎、皮膚そう、薬疹)、アレルギー性鼻炎、血管運動性鼻炎、感冒等上気道炎に伴うくしゃみ・鼻水・咳嗽に対して効果を示し、アレルギーや風邪の治療薬として一般的に使用されている。
It is generally said that the higher the molecular type fraction of a drug, the better the drug absorption (Non-patent Document 1). For basic drugs, the higher the pH, the higher the molecular fraction, so the higher the pH, the higher the absorbency, and for acidic drugs, the lower the pH, the higher the molecular fraction, The lower the value, the higher the absorbability.
Chlorpheniramine maleate, a typical basic drug, is one of the antihistamines. Urticaria, vasomotor edema, hay fever, pruritus associated with skin diseases (eczema, dermatitis, skin itch, drug eruption), allergic rhinitis, vasomotor rhinitis, cold, sneezing, runny nose, etc. It is effective against cough and is commonly used as a treatment for allergies and colds.
従来から、花粉やハウスダストなどに対する鼻アレルギーの症状を改善する為の対症療法として、鼻炎用医薬品である点鼻剤が知られている(非特許文献2)。
クロルフェニラミンマレイン酸塩を配合した点鼻剤は、アレルギー性鼻炎や花粉症などの治療に使用されている。花粉症による鼻炎症状を抑えるためには、花粉粒子からの抗原の溶出がアルカリ性側で高いため、点鼻剤のpHを弱酸性に調整しており(特許文献1)、このような弱酸性の点鼻剤では刺激を生じない。
Conventionally, nasal drops, which are drugs for rhinitis, are known as symptomatic treatments for improving the symptoms of nasal allergy to pollen and house dust (Non-patent Document 2).
Nasal drops containing chlorpheniramine maleate are used to treat allergic rhinitis and hay fever. In order to suppress the nasal inflammation caused by hay fever, the elution of the antigen from the pollen particles is high on the alkaline side, so the pH of the nasal drops is adjusted to be weakly acidic (Patent Document 1). Nose drops cause no irritation.
クロルフェニラミンマレイン酸塩を配合し、製剤のpHをアルカリ性側に設定した点鼻剤の報告はあるが(特許文献2)、刺激感を十分に緩和した技術は知られていない。 Although there is a report of a nasal drop containing chlorpheniramine maleate and setting the pH of the preparation to the alkaline side (Patent Document 2), there is no known technique that sufficiently reduces the irritation.
本発明は、塩基性薬物を含有する点鼻剤において、点鼻した際の刺激を緩和することを課題とする。 An object of the present invention is to alleviate irritation caused by nasal drop in a nasal drop containing a basic drug.
塩基性薬物の吸収性を高めるために点鼻剤のpHを7以上に設定すると、点鼻時に刺激を生じることを、本発明者らは発見した。
そこで、この問題を解決するために鋭意検討した結果、特定のポリエチレングリコールとグリセリンを配合することにより、塩基性薬物を配合する点鼻剤において生じる刺激を緩和できることを見出し、本発明を完成した。
すなわち本発明は、
(1)塩基性薬物、平均分子量が1300以上のポリエチレングリコール及びグリセリンを配合し、pHが7〜9であることを特徴とする点鼻剤、
(2)塩基性薬物が抗ヒスタミン薬である(1)に記載の点鼻剤、
(3)抗ヒスタミン薬がクロルフェニラミンマレイン酸塩である(2)に記載の点鼻剤、
(4)クロルフェニラミンマレイン酸塩の濃度が0.15w/v%以上である(3)に記載の点鼻剤、である。
The present inventors have discovered that when the pH of a nasal drop is set to 7 or more in order to enhance the absorbability of a basic drug, irritation occurs during nasal drop.
Thus, as a result of intensive studies to solve this problem, the inventors have found that by adding a specific polyethylene glycol and glycerin, it is possible to alleviate the irritation caused by a nasal drop containing a basic drug, thereby completing the present invention.
That is, the present invention
(1) A nasal preparation characterized by comprising a basic drug, polyethylene glycol having an average molecular weight of 1300 or more and glycerin, and having a pH of 7 to 9.
(2) Nasal agent according to (1), wherein the basic drug is an antihistamine;
(3) The nasal drop according to (2), wherein the antihistamine is chlorpheniramine maleate,
(4) The nasal drop according to (3), wherein the concentration of chlorpheniramine maleate is 0.15 w / v% or more.
本発明により、塩基性薬物を配合する点鼻剤において生じる刺激を緩和できる点鼻剤を提供することが可能になった。 According to the present invention, it has become possible to provide a nasal drop that can relieve irritation caused by a nasal drop containing a basic drug.
本発明の塩基性薬物としては、クロルフェニラミン、イソチペンジル、イプロヘプチン、ジフェテロール、ジフェニルピラリン、ジフェンヒドラミン、トリプロリジン、トリペレナミン、トンジルアミン、プロメタジン、メトジラジン、カルビノキサミン、アリメマジン、ジフェニルピラリン、アステミゾール、シクロヘプタジン、テルフェナジン、オキサトミド、アゼラスチン、エメダスチン、メキタジン、クレマスチン、エピナスチン、エフェドリン、テトラヒドロゾリン、オキシメタゾリン、ナファゾリン、フェニレフリン、メチルエフェドリン、リドカイン、デスモプレシン、スマトリプタン、カフェイン、プロプラノロール、またはその塩などが挙げられる。 Examples of the basic drug of the present invention include chlorpheniramine, isothipentyl, iproheptin, dipheterol, diphenylpyralin, diphenhydramine, triprolidine, tripelenamine, tondilamine, promethazine, methodirazine, carbinoxamine, alimemazine, diphenylpyralin, astemizole, cycloheptazine, terfenadine, Examples include oxatomide, azelastine, emedastine, mequitazine, clemastine, epinastine, ephedrine, tetrahydrozoline, oxymetazoline, naphazoline, phenylephrine, methylephedrine, lidocaine, desmopressin, sumatriptan, caffeine, propranolol, and salts thereof.
このうち、抗ヒスタミン薬としてはクロルフェニラミン、イソチペンジル、イプロヘプチン、ジフェテロール、ジフェニルピラリン、ジフェンヒドラミン、トリプロリジン、トリペレナミン、トンジルアミン、プロメタジン、メトジラジン、カルビノキサミン、アリメマジン、ジフェニルピラリン、アステミゾール、シクロヘプタジン、テルフェナジン、オキサトミド、アゼラスチン、エメダスチン、メキタジン、クレマスチン、エピナスチンが挙げられる。この中で最も好ましいのはクロルフェニラミンマレイン酸塩である。 Among these, the antihistamines include chlorpheniramine, isothipentyl, iproheptin, dipheterol, diphenylpyralin, diphenhydramine, triprolysine, tripelamine, tondilamine, promethazine, methodirazine, carbinoxamine, alimemazine, diphenylpyralin, astemizole, cycloheptazine, terfenadine, terfenadine, , Azelastine, emedastine, mequitazine, clemastine, and epinastine. Of these, chlorpheniramine maleate is most preferred.
塩基性薬物の配合濃度は適用する疾病の症状に応じて適宜増減することができる。ここで、本発明者らは、クロルフェニラミンマレイン酸塩が濃度依存的に鼻粘膜に刺激が生じることを発見した。すなわち、製剤中にクロルフェニラミンマレイン酸塩を0.15w/v%以上含有すると刺激を生じ、さらに濃度が高まると刺激を強く感じることを発見した。本発明の点鼻剤におけるクロルフェニラミンマレイン酸塩点鼻剤全体の0.15〜2.0w/v%であることが好ましい。 The concentration of the basic drug can be increased or decreased as appropriate according to the disease symptoms to be applied. Here, the present inventors have discovered that chlorpheniramine maleate stimulates the nasal mucosa in a concentration-dependent manner. That is, it has been found that when chlorpheniramine maleate is contained in an amount of 0.15 w / v% or more in the preparation, irritation occurs and when the concentration is further increased, irritation is felt strongly. The total amount of chlorpheniramine maleate nasal drops in the nasal drops of the present invention is preferably 0.15 to 2.0 w / v%.
本発明で用いるポリエチレングリコールは、多価アルコールであり、点鼻剤において本来溶解補助剤として用いられる成分である。平均分子量が1300以上のポリエチレングリコールとしては、PEG1540、PEG4000、PEG6000等が挙げられる。これらはグリセリンと組み合わせて使用することで、塩基性薬物を含有する点鼻剤の点鼻時の刺激を緩和することが可能である。平均分子量が1300未満のポリエチレングリコール、例えばPEG400等を使用しても効果は認められない。 Polyethylene glycol used in the present invention is a polyhydric alcohol and is a component that is originally used as a solubilizing agent in nasal drops. Examples of polyethylene glycol having an average molecular weight of 1300 or more include PEG 1540, PEG 4000, PEG 6000, and the like. By using these in combination with glycerin, it is possible to alleviate irritation during nasal drop of nasal drops containing a basic drug. Even if polyethylene glycol having an average molecular weight of less than 1300, such as PEG400, is used, no effect is observed.
また、ポリエチレングルコール以外の他の多価アルコールではグリセリンと組み合わせて使用しても点鼻時の刺激緩和効果は得られない。本発明は、平均分子量が1300以上のポリエチレングリコールに特異的な効果である。 In addition, when other polyhydric alcohols other than polyethylene glycol are used in combination with glycerin, no irritation mitigating effect can be obtained. The present invention has an effect specific to polyethylene glycol having an average molecular weight of 1300 or more.
さらに、本発明の平均分子量が1300以上のポリエチレングリコールの配合濃度は、好ましくは点鼻剤全体の0.25〜15.0w/v%である。0.25w/v%未満であると点鼻時の刺激緩和効果が不十分になる恐れがあるからである。 Furthermore, the blending concentration of polyethylene glycol having an average molecular weight of 1300 or more according to the present invention is preferably 0.25 to 15.0 w / v% of the whole nasal drop. This is because if it is less than 0.25 w / v%, the irritation mitigating effect may be insufficient.
また、本発明のグリセリンの配合濃度は必要に応じて適宜増減することができるが、点鼻剤全体の0.01〜6.0w/v%であることが好ましく、0.1〜2.0w/v%であることが更に好ましい。 Moreover, although the compounding density | concentration of the glycerol of this invention can be increased / decreased suitably as needed, it is preferable that it is 0.01-6.0 w / v% of the whole nasal drop, 0.1-2.0 w More preferably, it is / v%.
本発明の点鼻剤は、クロルフェニラミンマレイン酸塩、平均分子量が1300以上のポリエチレングリコール及びグリセリンを、精製水や生理食塩水に溶解することにより調製できる。さらに、点鼻剤用の噴霧器などに充填することにより点鼻剤として提供できる。 The nasal drops of the present invention can be prepared by dissolving chlorpheniramine maleate, polyethylene glycol having an average molecular weight of 1300 or more and glycerin in purified water or physiological saline. Furthermore, it can provide as a nasal drop by filling in a sprayer for nasal drops.
その際、本発明の効果を損なわない範囲で、他の有効成分として、ステロイド剤、血管収縮剤、抗炎症剤、局所麻酔剤、殺菌剤、収斂剤、清涼化剤等を配合することができる。また、ポリエチレングリコール以外の溶解補助剤、グリセリン以外の等張化剤、精製水やアルコールなどの溶剤、安定化剤、界面活性剤、清涼化剤、増粘剤、緩衝剤、防腐剤、pH調節剤、抗酸化剤、香料、色素のような各種添加剤を適宜添加してもよい。 At that time, steroid agents, vasoconstrictors, anti-inflammatory agents, local anesthetics, bactericides, astringents, cooling agents, etc. can be blended as other active ingredients within the range not impairing the effects of the present invention. . In addition, solubilizing agents other than polyethylene glycol, isotonic agents other than glycerin, solvents such as purified water and alcohol, stabilizers, surfactants, detergents, thickeners, buffers, preservatives, pH adjustment Various additives such as agents, antioxidants, fragrances, and pigments may be added as appropriate.
以下に、実施例、比較例及び試験例を示し、本発明を詳細に説明する。 Hereinafter, the present invention will be described in detail with reference to Examples, Comparative Examples and Test Examples.
(実施例1)
処方
クロルフェニラミンマレイン酸塩 200mg
ポリエチレングリコール4000 5000mg
グリセリン 2000mg
水酸化ナトリウム 適量
生理食塩水 全100mL
生理食塩水(約80mL)に各成分を溶解後、水酸化ナトリウムを適量添加し、pHを9.0に調整後、生理食塩水で全量を正確に100mLとした。これを点鼻剤用噴霧器に充填して点鼻剤とした。
Example 1
Prescription chlorpheniramine maleate 200mg
Polyethylene glycol 4000 5000mg
Glycerin 2000mg
Sodium hydroxide appropriate amount physiological saline all 100mL
After each component was dissolved in physiological saline (about 80 mL), an appropriate amount of sodium hydroxide was added to adjust the pH to 9.0, and then the total amount was accurately adjusted to 100 mL with physiological saline. This was filled into a nasal spray device to obtain a nasal spray.
(実施例2)
処方
クロルフェニラミンマレイン酸塩 500mg
ポリエチレングリコール1540 5000mg
グリセリン 2000mg
水酸化ナトリウム 適量
生理食塩水 全100mL
生理食塩水(約80mL)に各成分を溶解後、水酸化ナトリウムを適量添加し、pHを7.0に調整後、生理食塩水で全量を正確に100mLとした。これを点鼻剤用噴霧器に充填して点鼻剤とした。
(Example 2)
Prescription chlorpheniramine maleate 500mg
Polyethylene glycol 1540 5000mg
Glycerin 2000mg
Sodium hydroxide appropriate amount physiological saline all 100mL
After each component was dissolved in physiological saline (about 80 mL), an appropriate amount of sodium hydroxide was added to adjust the pH to 7.0, and the total amount was accurately adjusted to 100 mL with physiological saline. This was filled into a nasal spray device to obtain a nasal spray.
(実施例3)
処方
クロルフェニラミンマレイン酸塩 500mg
ポリエチレングリコール4000 5000mg
グリセリン 2000mg
水酸化ナトリウム 適量
生理食塩水 全100mL
生理食塩水(約80mL)に各成分を溶解後、水酸化ナトリウムを適量添加し、pHを7.0に調整後、生理食塩水で全量を正確に100mLとした。これを点鼻剤用噴霧器に充填して点鼻剤とした。
(Example 3)
Prescription chlorpheniramine maleate 500mg
Polyethylene glycol 4000 5000mg
Glycerin 2000mg
Sodium hydroxide appropriate amount physiological saline all 100mL
After each component was dissolved in physiological saline (about 80 mL), an appropriate amount of sodium hydroxide was added to adjust the pH to 7.0, and the total amount was accurately adjusted to 100 mL with physiological saline. This was filled into a nasal spray device to obtain a nasal spray.
(実施例4)
処方
クロルフェニラミンマレイン酸塩 500mg
ポリエチレングリコール6000 5000mg
グリセリン 2000mg
水酸化ナトリウム 適量
生理食塩水 全100mL
生理食塩水(約80mL)に各成分を溶解後、水酸化ナトリウムを適量添加し、pHを7.0に調整後、生理食塩水で全量を正確に100mLとした。これを点鼻剤用噴霧器に充填して点鼻剤とした。
Example 4
Prescription chlorpheniramine maleate 500mg
Polyethylene glycol 6000 5000mg
Glycerin 2000mg
Sodium hydroxide appropriate amount physiological saline all 100mL
After each component was dissolved in physiological saline (about 80 mL), an appropriate amount of sodium hydroxide was added to adjust the pH to 7.0, and the total amount was accurately adjusted to 100 mL with physiological saline. This was filled into a nasal spray device to obtain a nasal spray.
(実施例5)
処方
クロルフェニラミンマレイン酸塩 2000mg
ポリエチレングリコール4000 5000mg
グリセリン 2000mg
水酸化ナトリウム 適量
生理食塩水 全100mL
生理食塩水(約80mL)に各成分を溶解後、水酸化ナトリウムを適量添加し、pHを8.0に調整後、生理食塩水で全量を正確に100mLとした。これを点鼻剤用噴霧器に充填して点鼻剤とした。
(Example 5)
Prescription chlorpheniramine maleate 2000mg
Polyethylene glycol 4000 5000mg
Glycerin 2000mg
Sodium hydroxide appropriate amount physiological saline all 100mL
After each component was dissolved in physiological saline (about 80 mL), an appropriate amount of sodium hydroxide was added to adjust the pH to 8.0, and the total amount was accurately adjusted to 100 mL with physiological saline. This was filled into a nasal spray device to obtain a nasal spray.
(実施例6)
処方
クロルフェニラミンマレイン酸塩 150mg
ポリエチレングリコール4000 5000mg
グリセリン 2000mg
水酸化ナトリウム 適量
生理食塩水 全100mL
生理食塩水(約80mL)に各成分を溶解後、水酸化ナトリウムを適量添加し、pHを9.0に調整後、生理食塩水で全量を正確に100mLとした。これを点鼻剤用噴霧器に充填して点鼻剤とした。
(Example 6)
Prescription chlorpheniramine maleate 150mg
Polyethylene glycol 4000 5000mg
Glycerin 2000mg
Sodium hydroxide appropriate amount physiological saline all 100mL
After each component was dissolved in physiological saline (about 80 mL), an appropriate amount of sodium hydroxide was added to adjust the pH to 9.0, and then the total amount was accurately adjusted to 100 mL with physiological saline. This was filled into a nasal spray device to obtain a nasal spray.
(実施例7)
処方
クロルフェニラミンマレイン酸塩 200mg
ポリエチレングリコール4000 250mg
グリセリン 2000mg
水酸化ナトリウム 適量
生理食塩水 全100mL
生理食塩水(約80mL)に各成分を溶解後、水酸化ナトリウムを適量添加し、pHを9.0に調整後、生理食塩水で全量を正確に100mLとした。これを点鼻剤用噴霧器に充填して点鼻剤とした。
(Example 7)
Prescription chlorpheniramine maleate 200mg
Polyethylene glycol 4000 250mg
Glycerin 2000mg
Sodium hydroxide appropriate amount physiological saline all 100mL
After each component was dissolved in physiological saline (about 80 mL), an appropriate amount of sodium hydroxide was added to adjust the pH to 9.0, and then the total amount was accurately adjusted to 100 mL with physiological saline. This was filled into a nasal spray device to obtain a nasal spray.
(実施例8)
処方
クロルフェニラミンマレイン酸塩 200mg
ポリエチレングリコール4000 500mg
グリセリン 2000mg
水酸化ナトリウム 適量
生理食塩水 全100mL
生理食塩水(約80mL)に各成分を溶解後、水酸化ナトリウムを適量添加し、pHを9.0に調整後、生理食塩水で全量を正確に100mLとした。これを点鼻剤用噴霧器に充填して点鼻剤とした。
(Example 8)
Prescription chlorpheniramine maleate 200mg
Polyethylene glycol 4000 500mg
Glycerin 2000mg
Sodium hydroxide appropriate amount physiological saline all 100mL
After each component was dissolved in physiological saline (about 80 mL), an appropriate amount of sodium hydroxide was added to adjust the pH to 9.0, and then the total amount was accurately adjusted to 100 mL with physiological saline. This was filled into a nasal spray device to obtain a nasal spray.
(比較例1)
処方
クロルフェニラミンマレイン酸塩 200mg
水酸化ナトリウム 適量
生理食塩水 全100mL
生理食塩水(約80mL)に各成分を溶解後、水酸化ナトリウムを適量添加し、pHを6.0に調整後、生理食塩水で全量を正確に100mLとした。これを点鼻剤用噴霧器に充填して点鼻剤とした。
(Comparative Example 1)
Prescription chlorpheniramine maleate 200mg
Sodium hydroxide appropriate amount physiological saline all 100mL
After each component was dissolved in physiological saline (about 80 mL), an appropriate amount of sodium hydroxide was added to adjust the pH to 6.0, and then the total amount was accurately adjusted to 100 mL with physiological saline. This was filled into a nasal spray device to obtain a nasal spray.
(比較例2)
処方
クロルフェニラミンマレイン酸塩 200mg
水酸化ナトリウム 適量
生理食塩水 全100mL
生理食塩水(約80mL)に各成分を溶解後、水酸化ナトリウムを適量添加し、pHを9.0に調整後、生理食塩水で全量を正確に100mLとした。これを点鼻剤用噴霧器に充填して点鼻剤とした。
(Comparative Example 2)
Prescription chlorpheniramine maleate 200mg
Sodium hydroxide appropriate amount physiological saline all 100mL
After each component was dissolved in physiological saline (about 80 mL), an appropriate amount of sodium hydroxide was added to adjust the pH to 9.0, and then the total amount was accurately adjusted to 100 mL with physiological saline. This was filled into a nasal spray device to obtain a nasal spray.
(比較例3)
処方
クロルフェニラミンマレイン酸塩 100mg
水酸化ナトリウム 適量
生理食塩水 全100mL
生理食塩水(約80mL)に各成分を溶解後、水酸化ナトリウムを適量添加し、pHを9.0に調整後、生理食塩水で全量を正確に100mLとした。これを点鼻剤用噴霧器に充填して点鼻剤とした。
(Comparative Example 3)
Prescription chlorpheniramine maleate 100mg
Sodium hydroxide appropriate amount physiological saline all 100mL
After each component was dissolved in physiological saline (about 80 mL), an appropriate amount of sodium hydroxide was added to adjust the pH to 9.0, and then the total amount was accurately adjusted to 100 mL with physiological saline. This was filled into a nasal spray device to obtain a nasal spray.
(比較例4)
処方
クロルフェニラミンマレイン酸塩 150mg
水酸化ナトリウム 適量
生理食塩水 全100mL
生理食塩水(約80mL)に各成分を溶解後、水酸化ナトリウムを適量添加し、pHを9.0に調整後、生理食塩水で全量を正確に100mLとした。これを点鼻剤用噴霧器に充填して点鼻剤とした。
(Comparative Example 4)
Prescription chlorpheniramine maleate 150mg
Sodium hydroxide appropriate amount physiological saline all 100mL
After each component was dissolved in physiological saline (about 80 mL), an appropriate amount of sodium hydroxide was added to adjust the pH to 9.0, and then the total amount was accurately adjusted to 100 mL with physiological saline. This was filled into a nasal spray device to obtain a nasal spray.
(比較例5)
処方
クロルフェニラミンマレイン酸塩 200mg
ポリエチレングリコール4000 5000mg
水酸化ナトリウム 適量
生理食塩水 全100mL
生理食塩水(約80mL)に各成分を溶解後、水酸化ナトリウムを適量添加し、pHを9.0に調整後、生理食塩水で全量を正確に100mLとした。これを点鼻剤用噴霧器に充填して点鼻剤とした。
(Comparative Example 5)
Prescription chlorpheniramine maleate 200mg
Polyethylene glycol 4000 5000mg
Sodium hydroxide appropriate amount physiological saline all 100mL
After each component was dissolved in physiological saline (about 80 mL), an appropriate amount of sodium hydroxide was added to adjust the pH to 9.0, and then the total amount was accurately adjusted to 100 mL with physiological saline. This was filled into a nasal spray device to obtain a nasal spray.
(比較例6)
処方
クロルフェニラミンマレイン酸塩 200mg
グリセリン 2000mg
水酸化ナトリウム 適量
生理食塩水 全100mL
生理食塩水(約80mL)に各成分を溶解後、水酸化ナトリウムを適量添加し、pHを9.0に調整後、生理食塩水で全量を正確に100mLとした。これを点鼻剤用噴霧器に充填して点鼻剤とした。
(Comparative Example 6)
Prescription chlorpheniramine maleate 200mg
Glycerin 2000mg
Sodium hydroxide appropriate amount physiological saline all 100mL
After each component was dissolved in physiological saline (about 80 mL), an appropriate amount of sodium hydroxide was added to adjust the pH to 9.0, and then the total amount was accurately adjusted to 100 mL with physiological saline. This was filled into a nasal spray device to obtain a nasal spray.
(比較例7)
処方
クロルフェニラミンマレイン酸塩 200mg
プロピレングリコール 5000mg
グリセリン 2000mg
水酸化ナトリウム 適量
生理食塩水 全100mL
生理食塩水(約80mL)に各成分を溶解後、水酸化ナトリウムを適量添加し、pHを9.0に調整後、生理食塩水で全量を正確に100mLとした。これを点鼻剤用噴霧器に充填して点鼻剤とした。
(Comparative Example 7)
Prescription chlorpheniramine maleate 200mg
Propylene glycol 5000mg
Glycerin 2000mg
Sodium hydroxide appropriate amount physiological saline all 100mL
After each component was dissolved in physiological saline (about 80 mL), an appropriate amount of sodium hydroxide was added to adjust the pH to 9.0, and then the total amount was accurately adjusted to 100 mL with physiological saline. This was filled into a nasal spray device to obtain a nasal spray.
(比較例8)
処方
クロルフェニラミンマレイン酸塩 500mg
水酸化ナトリウム 適量
生理食塩水 全100mL
生理食塩水(約80mL)に各成分を溶解後、水酸化ナトリウムを適量添加し、pHを7.0に調整後、生理食塩水で全量を正確に100mLとした。これを点鼻剤用噴霧器に充填して点鼻剤とした。
(Comparative Example 8)
Prescription chlorpheniramine maleate 500mg
Sodium hydroxide appropriate amount physiological saline all 100mL
After each component was dissolved in physiological saline (about 80 mL), an appropriate amount of sodium hydroxide was added to adjust the pH to 7.0, and the total amount was accurately adjusted to 100 mL with physiological saline. This was filled into a nasal spray device to obtain a nasal spray.
(比較例9)
処方
クロルフェニラミンマレイン酸塩 500mg
ポリエチレングリコール400 5000mg
グリセリン 2000mg
水酸化ナトリウム 適量
生理食塩水 全100mL
生理食塩水(約80mL)に各成分を溶解後、水酸化ナトリウムを適量添加し、pHを7.0に調整後、生理食塩水で全量を正確に100mLとした。これを点鼻剤用噴霧器に充填して点鼻剤とした。
(Comparative Example 9)
Prescription chlorpheniramine maleate 500mg
Polyethylene glycol 400 5000mg
Glycerin 2000mg
Sodium hydroxide appropriate amount physiological saline all 100mL
After each component was dissolved in physiological saline (about 80 mL), an appropriate amount of sodium hydroxide was added to adjust the pH to 7.0, and the total amount was accurately adjusted to 100 mL with physiological saline. This was filled into a nasal spray device to obtain a nasal spray.
(試験例)
下表1〜5記載の実施例及び比較例で得た点鼻剤を点鼻剤用噴霧器に充填した。健常人2〜3名に対し、点鼻剤を鼻腔に噴霧し、刺激感の程度を0〜4(0は刺激感なし、1はほぼ刺激感なし、2は刺激を感じる、3はやや刺激が強い、4は刺激が強い)にスコア化して評価した。刺激緩和目標値を1以下と設定した。結果を同表下欄に記載する。処方の数値は「mg/100mL」で示した。
(Test example)
The nasal drops obtained in the examples and comparative examples described in Tables 1 to 5 below were filled in a nasal spray device. For 2 to 3 healthy people, spray nasal drops on the nasal cavity, and the degree of irritation is 0-4 (0 is no irritation, 1 is almost no irritation, 2 is irritation, 3 is slightly irritation (4 is strong and irritation is strong). The stimulation alleviation target value was set to 1 or less. The results are listed in the lower column of the table. The numerical value of the prescription was shown as “mg / 100 mL”.
上表3より、比較例2〜4において、クロルフェニラミンマレイン酸塩を、0.15質量%以上含有すると刺激を生じ、濃度依存的に刺激を強く感じることが分かった。また、比較例1より、クロルフェニラミンマレイン酸塩が0.2質量%配合されても、pH6では刺激感を生じなかった。 From Table 3 above, in Comparative Examples 2 to 4, it was found that when chlorpheniramine maleate was contained in an amount of 0.15% by mass or more, irritation occurred and the irritation was strongly felt in a concentration-dependent manner. Further, from Comparative Example 1, even when 0.2% by mass of chlorpheniramine maleate was added, no irritation was felt at pH 6.
本発明にかかる実施例1〜8の点鼻剤は、比較例2、4〜9の点鼻剤と比較して鼻粘膜への刺激が緩和された。本発明で用いるポリエチレングリコールは、多価アルコールであるが、他の多価アルコール(プロピレングリコール)では、鼻粘膜への刺激緩和効果は得られず、ポリエチレングリコールに特異的な効果であった。本発明により、塩基性薬物、特にクロルフェニラミンマレイン酸塩を配合する点鼻剤において生じる点鼻時の刺激を緩和出来る極めて有用な点鼻剤を提供することが可能となった。また、点鼻剤が高pHに設定されているので、塩基性薬物の吸収性が増加することで薬物量の低減などが期待される。 The nasal drops of Examples 1 to 8 according to the present invention alleviated irritation to the nasal mucosa as compared with the nasal drops of Comparative Examples 2 and 4 to 9. The polyethylene glycol used in the present invention is a polyhydric alcohol, but other polyhydric alcohols (propylene glycol) did not provide an effect of alleviating irritation to the nasal mucosa and were specific to polyethylene glycol. INDUSTRIAL APPLICABILITY According to the present invention, it has become possible to provide a very useful nasal drop that can relieve irritation caused by a nasal drop that occurs in a nasal drop containing a basic drug, particularly chlorpheniramine maleate. In addition, since the nasal drops are set to a high pH, it is expected that the amount of the drug will be reduced by increasing the absorbability of the basic drug.
塩基性薬物を含有し、刺激の緩和されたpH7〜9の点鼻剤の提供が可能となった。 It became possible to provide a nasal drop containing a basic drug and having a relaxed pH of 7-9.
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2011250593A JP5879945B2 (en) | 2010-11-30 | 2011-11-16 | Nasal drops |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010266303 | 2010-11-30 | ||
JP2010266303 | 2010-11-30 | ||
JP2011250593A JP5879945B2 (en) | 2010-11-30 | 2011-11-16 | Nasal drops |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2012131774A JP2012131774A (en) | 2012-07-12 |
JP5879945B2 true JP5879945B2 (en) | 2016-03-08 |
Family
ID=46647810
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2011250593A Active JP5879945B2 (en) | 2010-11-30 | 2011-11-16 | Nasal drops |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP5879945B2 (en) |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5897858A (en) * | 1994-02-03 | 1999-04-27 | Schering-Plough Healthcare Products, Inc. | Nasal spray compositions exhibiting increased retention in the nasal cavity |
JP2001247446A (en) * | 2000-03-06 | 2001-09-11 | Toa Yakuhin Kk | Cleaning agent with deep sea water |
JP2004018432A (en) * | 2002-06-14 | 2004-01-22 | Lion Corp | Temperature-sensitive composition for ophthalmology or otorhinology |
JP5163845B2 (en) * | 2006-10-19 | 2013-03-13 | ライオン株式会社 | Spray |
-
2011
- 2011-11-16 JP JP2011250593A patent/JP5879945B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
JP2012131774A (en) | 2012-07-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10987352B2 (en) | Ophthalmic formulations of cetirizine and methods of use | |
RU2607892C2 (en) | Composition based on xylitol, preventing separation of slime and related methods and compositions | |
JP5794744B2 (en) | Stabilized ophthalmic galactomannan formulation | |
ES2830447T3 (en) | Method for the prevention and / or treatment of cognitive impairment associated with aging and neuroinflammation | |
JP2020097624A (en) | Treatment of allergic rhinitis using combination of mometasone and olopatadine | |
JP2018506570A5 (en) | ||
CN107847433B (en) | Nasal composition | |
JP2009196983A (en) | Ophthalmic composition | |
JP2013237638A (en) | Ophthalmic composition | |
AR039409A1 (en) | PHARMACEUTICAL COMPOSITION IN DRY POWDER FOR INHALATION, MANUFACTURE AND USE. | |
AU2003278962C1 (en) | Nasal compositions comprising a mucopolysaccharide and propylene glycol | |
JP5879945B2 (en) | Nasal drops | |
JP2002114686A (en) | Eye drop composition | |
JP5834427B2 (en) | Adsorption suppression method for soft contact lenses | |
EA030949B1 (en) | Pharmaceutical composition in the form of an oral suspension including a flavonoid fraction and xanthan gum | |
CN100496491C (en) | Mebendazole new formulation for treating chronic rhinitis | |
JP5560588B2 (en) | Ophthalmic agent | |
WO2017123424A1 (en) | Nasal spray | |
JP4614423B2 (en) | Nasal composition for allergic rhinitis | |
JP2005047816A (en) | Nasal drop comprising alkali metal azulenesulfonate | |
JP2004168762A (en) | Nose drop preparation composition | |
CN100446765C (en) | Albendazole new form for treating chronic rhinitis | |
JP2005097221A (en) | Nasal drop | |
JP2003055206A (en) | Medicine composition for nasal cavity | |
JP2009185006A (en) | Nose drop or eye drop |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20141104 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150526 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20150529 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150717 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20160105 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160118 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5879945 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |