JP7002756B2 - 局所と局部の麻酔と鎮痛 - Google Patents
局所と局部の麻酔と鎮痛 Download PDFInfo
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Description
本出願は2015年11月5日に出願されたアメリカ仮出願シリアル番号62/251、162の優先権を主張し、この文献の全ての開示がこの参照により本明細書に組み込まれる。
本発明はアメリカ国立衛生研究所により与えられた補助金ナンバー1U01HL127518下の政府の支援の元で行われた。政府は本発明に対する所定の権利を有する。
今開示される主題は、対象者の神経組織内で局所(local)または局部(regional)の麻酔と鎮痛を生じさせるための医薬組成物と方法に関連する。特に、今開示される主題は対象者へアチパメゾールの有効量を投与することによる、対象者の神経組織内で局所または局部の麻酔と鎮痛を生じさせることに関連する。
数百万人の人々が、局所麻酔薬が軽減できる持続性の痛みを経験している。けれども、現在の局所麻酔薬は著しい安全性と毒性の問題がある。例えば、毎年1億6千万人以上の人々が、慢性痛の状態のものも含む数日以上続く穏やかから激しい目の痛みを経験している。これらの多くが、局所/経口NSAIDsおよび麻薬があるにもかかわらず残存する痛みを有する。局所麻酔薬は完全な痛みの軽減を提供するが、しかし、数時間を超えて使用することは傷の回復の遅れや角膜劣化の重大な危険性のために認可されていない。
今開示される主題は、局所または局部の麻酔もしくは鎮痛を生じさせるための医薬組成物および方法を含み、それらは現在の薬剤や方法に関連する不都合を有さない。
本方法のいくつかの実施形態において、補助剤はエピネフリン、麻薬、ブプレノルフィン、筋弛緩薬、非ステロイド性抗炎症薬、ヒアルロニダーゼ、重炭酸塩およびデキサメタゾンから選択される。
いくつかの実施形態において、補助剤は、エピネフリン、麻薬、ブプレノルフィン、筋弛緩薬、非ステロイド性抗炎症薬(トラドールのような)、ヒアルロニダーゼ、重炭酸塩およびデキサメタゾンから選択される。
今開示される主題の一つあるいはより多くの実施形態の詳細がこの書類に記載される。この書類に記載された実施形態への修正およびその他の実施形態は、この書類の中で提供される情報の研究後に当業者に明白になるだろう。この書類の中で提供される情報、特に、記載された具体的な実施形態の具体的詳細は、主に理解の明確のために提供され、不必要な限定がそれから理解されるべきでない。係争の際は、定義を含むこの書類の明細書が支配する。
アチップが感覚あるいは運動ニューロンに異なる働きをするかどうかを測定するために、外科的動物標本が用いられた。その手順はPetruskaら1998(Experimental Brain Research 121:379-390)に記載されたのと同様であった。簡潔に言うと、成熟したラットは、ケタミン/キシラジンで一般的な麻酔薬を受けた。頸静脈、頸動脈、そして気管は、補足の麻酔薬を投与、血圧の測定、終末呼気のCO2の測定のためにそれぞれ挿管された。通常の体温は、水ベースの熱毛布(water-based thermal blanket)により1℃以内に維持された。椎弓切除(T13~L2)はL4-L6の背根と腹根を曝すために行われ、脊髄から切開された。
生細胞のカルシウムを画像化する研究が、死後の提供者から分離されたヒトDRGニューロンで行われた。細胞は0.1%プルロニックF-127(シグマ P2443)を含む3μM フルオ 8-AM(AAT Bioquest 21081)で20分間負荷された。細胞外の溶液はmM単位で(シグマ):145 塩化ナトリウム(S3014)、3 塩化カリウム(P3911)、2 塩化カルシウム(C3881)、1 塩化マグネシウム(M9272)、10 ヘペス(H3375)、10 グルコース(G5767)を含み、水酸化ナトリウム(72068)によってPH7.4に調整した。フルオ-8-負荷細胞は480nmで励起され、倒立顕微鏡(オリンパスIX71)に取り付けられたpcoEDGE sCMOS カメラ(PCO)を用いて520nmの発光が集められた。
細胞毒性に関する研究は、ヒトテロメラーゼ不死化ヒト角膜上皮細胞(hTCEpi細胞:細胞はゲノンコーポレーション、メンローパーク、カリフォルニア、アメリカを通して得られた)を使って行われた。細胞を、成長培地(成長補助剤を有する規定のケラチン生成細胞培地、インビトロジェン、グランドアイランド、ニューヨーク、アメリカ)を入れた96ウェル皿の1ウェルあたり30、000細胞の密度で培養した。24時間のリカバリー(recovery)後、成長培地単独または0.5%のDMSO(ビヒクル)、指示された濃度のアチップもしくは0.5%のプロパラカイン(アコーン、フォレストレイク、イェール)が補充された成長培地のいずれかで細胞を処理した。細胞を24あるいは48時間、37℃、5%二酸化炭素でインキュベートした。細胞の生存能力をAlamar Blue Assay(サーモフィッシャー、ウォルサム、マサチューセッツ、アメリカ)を使って評価した。
研究は、脱分極電流によって誘導された活動電位へのアチップ投与の効果を調べるために行われた。外傷感受性解離ラット感覚ニューロンにおける電気生理学現象を、以前に記載されたパッチ-クランプ法(5)を用いて記録した。
アチップの効果を試験する研究も、α2受容体サブユニットノックアウトマウスで行われた。本研究ではα2A ARノックアウトとα2C ARノックアウトマウスを用いた。動物は、5mMのアチップを右足底の皮下に、そしてビヒクルを左足底の皮下に注射された。次いで、それぞれの足の皮膚と足の肉趾を強くつねった。右および左の足のつねりに対するひっこみ反応が評価された。
1. The Gallup Organization, I. (2008) The 20008 Gallup Study of Dry Eye Sufferers. Princeton, NJ
2. Rush, J. S., Boeving, M. A., Berry, W. L., and Ceresa, B. P. (2014). Antagonizing c-Cbl enhances EGFR-dependent corneal epithelial homeostasis. Invest Ophthalmol Vis Sci 55, 4691-4699
3. Boljka, M., Kolar, G., and Vidensek, J. (1994). Toxic side effects of local anaesthetics on the human cornea. Br J Ophthalmol 78, 386-389
4. Petruska, J. C., Barker, D. F., Garraway, S. M., Trainer, R., Fransen, J. W., Seidman, P. A., Soto, R. G., Mendell, L. M., and Johnson, R. D. (2014). Organization of sensory input to the nociceptive-specific cutaneous trunk muscle reflex in rat, an effective experimental system for examining nociception and plasticity. J Comp Neurol 522, 1048-1071
5. Rau, K. K., Hill, C. E., Harrison, B. J., Venkat, G., Koenig, H. M., Cook, S. B., Rabchevsky, A. G., Taylor, B. K., Hai, T., and Petruska, J. C. (2016). Cutaneous tissue damage induces long-lasting nociceptive sensitization and regulation of cellular stress- and nerve injury-associated genes in sensory neurons. Exp Neurol 283, 413-427
6. Theriault, E., and Diamond, J. (1988). Intrinsic organization of the rat cutaneus trunci motor nucleus. J Neurophysiol 60, 463-477
7. Theriault, E., and Diamond, J. (1988). Nociceptive cutaneous stimuli evoke localized contractions in a skeletal muscle. J Neurophysiol 60, 446-462
8. Petruska, J. C., Barker, D. F., Garraway, S. M., Trainer, R., Fransen, J. W., Seidman, P. A., Soto, R. G., Mendell, L. M., and Johnson, R. D. (2013). Organization of sensory input to the nociceptive-specific cutaneous trunk muscle reflex in rat, an effective experimental system for examining nociception and plasticity. The Journal of comparative neurology
9. Huang, Y., Gil, D. W., Vanscheeuwijck, P., Stamer, W. D., and Regan, J. W. (1995). Localization of alpha 2-adrenergic receptor subtypes in the anterior segment of the human eye with selective antibodies. Invest Ophthalmol Vis Sci 36, 2729-2739
10. Woldemussie, E., Wijono, M., and Pow, D. (2007). Localization of alpha 2 receptors in ocular tissues. Vis Neurosci 24, 745-756
12. Takagi, Y., Osaki, H., Yamashita, T., and Kai, Y. (2016). Prospective Observational Post-marketing Study of Tafluprost 0.0015%/Timolol 0.5% Combination Ophthalmic Solution for Glaucoma and Ocular Hypertension: Short-Term Efficacy and Safety. Ophthalmol Ther
13. Berlan, M., Verhaeghe, S., Pavy-Le Traon, A., Thalamas, C., Lafontan, M., Marques, M. A., Senard, J. M., Parent, M., and Galitzky, J. (2002). Yohimbine administration prevents over-responsiveness to epinephrine induced by simulated microgravity. Aviat Space Environ Med 73, 735-742
14. Christoph, T., Schroder, W., Tallarida, R. J., De Vry, J., and Tzschentke, T. M. (2013). Spinal-supraspinal and intrinsic mu-opioid receptor agonist-norepinephrine reuptake inhibitor (MOR-NRI) synergy of tapentadol in diabetic heat hyperalgesia in mice. J Pharmacol Exp Ther 347, 794-801
15. de Tejada, I. S., Garvey, D. S., Schroeder, J. D., Shelekhin, T., Letts, L. G., Fernandez, A., Cuevas, B., Gabancho, S., Martinez, V., Angulo, J., Trocha, M., Marek, P., Cuevas, P., and Tam, S. W. (1999). Design and evaluation of nitrosylated alpha-adrenergic receptor antagonists as potential agents for the treatment of impotence. J Pharmacol Exp Ther 290, 121-128
16. Karhuvaara, S., Kallio, A., Scheinin, M., Anttila, M., Salonen, J. S., and Scheinin, H. (1990). Pharmacological effects and pharmacokinetics of atipamezole, a novel alpha 2-adrenoceptor antagonist--a randomized, double-blind cross-over study in healthy male volunteers. Br J Clin Pharmacol 30, 97-106
17. Huupponen, R., Karhuvaara, S., Anttila, M., Vuorilehto, L., and Scheinin, H. (1995). Buccal delivery of an alpha 2-adrenergic receptor antagonist, atipamezole, in humans. Clin Pharmacol Ther 58, 506-511
18. Friedenwald, J. S., and Buschke, W. (1944). Some Factors Concerned in the Mitotic and Wound-Healing Activities of the Corneal Epithelium. Trans Am Ophthalmol Soc 42, 371-383
19. Wang, S. B., Hu, K. M., Seamon, K. J., Mani, V., Chen, Y., and Gronert, K. (2012). Estrogen negatively regulates epithelial wound healing and protective lipid mediator circuits in the cornea. FASEB J 26, 1506-1516
20. Meng, I. D., Barton, S. T., Mecum, N. E., and Kurose, M. (2015). Corneal sensitivity following lacrimal gland excision in the rat. Invest Ophthalmol Vis Sci 56, 3347-3354
22. Judge, A. J., Najafi, K., Lee, D. A., and Miller, K. M. (1997). Corneal endothelial toxicity of topical anesthesia. Ophthalmology 104, 1373-1379
23. Kadonosono, K., Ito, N., Yazama, F., Nishide, T., Sugita, M., Sawada, H., and Ohno, S. (1998). Effect of intracameral anesthesia on the corneal endothelium. J Cataract Refract Surg 24, 1377-1381
24. Kim, W. J., Shah, S., and Wilson, S. E. (1998). Differences in keratocyte apoptosis following transepithelial and laser-scrape photorefractive keratectomy in rabbits. J Refract Surg 14, 526-533
25. Stepp, M. A., Spurr-Michaud, S., and Gipson, I. K. (1993). Integrins in the wounded and unwounded stratified squamous epithelium of the cornea. Invest Ophthalmol Vis Sci 34, 1829-1844
26. Peterson, J. L., Phelps, E. D., Doll, M. A., Schaal, S., and Ceresa, B. P. (2014). The role of endogenous epidermal growth factor receptor ligands in mediating corneal epithelial homeostasis. Invest Ophthalmol Vis Sci 55, 2870-2880
27. Rau, K. K., Petruska, J. C., Cooper, B. Y., and Johnson, R. D. (2014). Distinct subclassification of DRG neurons innervating the distal colon and glans penis/distal urethra based on the electrophysiological current signature. J Neurophysiol 112, 1392-1408
28. Petruska, J. C., Napaporn, J., Johnson, R. D., and Cooper, B. Y. (2002). Chemical responsiveness and histochemical phenotype of electrophysiologically classified cells of the adult rat dorsal root ganglion. Neuroscience 115, 15-30
29. McAlvin, J. B., Zhan, C., Dohlman, J. C., Kolovou, P. E., Salvador-Culla, B., and Kohane, D. S. (2015). Corneal Anesthesia With Site 1 Sodium Channel Blockers and Dexmedetomidine. Invest Ophthalmol Vis Sci 56, 3820-3826
30. Sjoholm, B., Lahdesmaki, J., Pyykko, K., Hillila, M., and Scheinin, M. (1999). Non-adrenergic binding of [3H]atipamezole in rat kidney--regional distribution and comparison to alpha2-adrenoceptors. Br J Pharmacol 128, 1215-1222
32. Wei, H., and Pertovaara, A. (2006). Spinal and pontine alpha2-adrenoceptors have opposite effects on pain-related behavior in the neuropathic rat. Eur J Pharmacol 551, 41-49
33. Sjoholm, B., Savola, J. M., and Scheinin, M. (1995). Nonadrenergic binding of [3H]atipamezole in rat lung. A novel imidazole binding site? Ann N Y Acad Sci 763, 66-77
34. Sjoholm, B., Voutilainen, R., Luomala, K., Savola, J. M., and Scheinin, M. (1992). Characterization of [3H]atipamezole as a radioligand for alpha 2-adrenoceptors. Eur J Pharmacol 215, 109-117
35. Koerber, H. R., Druzinsky, R. E., and Mendell, L. M. (1988). Properties of somata of spinal dorsal root ganglion cells differ according to peripheral receptor innervated. J Neurophysiol 60, 1584-1596
36. Lopez de Armentia, M., Cabanes, C., and Belmonte, C. (2000). Electrophysiological properties of identified trigeminal ganglion neurons innervating the cornea of the mouse. Neuroscience 101, 1109-1115
37. Huang, J., Yang, Y., Dib-Hajj, S. D., van Es, M., Zhao, P., Salomon, J., Drenth, J. P., and Waxman, S. G. (2014). Depolarized inactivation overcomes impaired activation to produce DRG neuron hyperexcitability in a Nav1.7 mutation in a patient with distal limb pain. J Neurosci 34, 12328-12340
38. Park, J., Werley, C. A., Venkatachalam, V., Kralj, J. M., Dib-Hajj, S. D., Waxman, S. G., and Cohen, A. E. (2013). Screening fluorescent voltage indicators with spontaneously spiking HEK cells. PLoS One 8, e85221
39. Jahnsen, J. A., and Uhlen, S. (2013). The C-terminal half of the alpha2C-adrenoceptor determines the receptor's membrane expression level and drug selectivity. Naunyn Schmiedebergs Arch Pharmacol 386, 1031-1040
40. Rush, A. M., Cummins, T. R., and Waxman, S. G. (2007). Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons. J Physiol 579, 1-14
42. Fan, S. F., Shen, K. F., Scheideler, M. A., and Crain, S. M. (1992). F11 neuroblastoma x DRG neuron hybrid cells express inhibitory mu- and delta-opioid receptors which increase voltage-dependent K+ currents upon activation. Brain Res 590, 329-333
43. Wieringa, P., Tonazzini, I., Micera, S., and Cecchini, M. (2012). Nanotopography induced contact guidance of the F11 cell line during neuronal differentiation: a neuronal model cell line for tissue scaffold development. Nanotechnology 23, 275102
44. Ceresa, B. P., and Limbird, L. E. (1994). Mutation of an aspartate residue highly conserved among G-protein coupled receptors results in nonreciprocal disruption of alpha2a-adrenergic receptor-G-protein interactions. J Biol Chem 272, 12121-12124
45. Grant, R. L., and Acosta, D. (1994). Comparative toxicity of tetracaine, proparacaine and cocaine evaluated with primary cultures of rabbit corneal epithelial cells. Exp Eye Res 58, 469-478
46. Farley, D. B., Ford, S. P., Reynolds, L. P., Bhatnagar, R. K., and Van Orden, D. E. (1984). Quantitation of alpha 1-adrenergic receptors in porcine uterine and mesenteric arteries. Am J Obstet Gynecol 150, 485-491
47. Kosugi, T., et al., (2010) High concentrations of dexmedetomidine inhibit compound action potentials in frog sciatic nerves without a2 adrenoceptor activation, British Journal of Pharmacology.
48. Maruta, et al., (2011) Dexmedetomidine and clonidine inhibit the function of Nav1.7 independent of α2-adrenoceptor in adrenal chromaffin cells, J. Anesth 25:549-557.
49. Leem, et al., (2000) Conduction Block by Clonidine is Not Mediated by α2-Adrenergic Receptors in Rat Sciatic Nerve Fibers, Regional Anesthesia and Pain Medicine 25(6): 620-625.
50. Jackson and Ceresa, (2016) Protein Kinase G facilitates EGFR-mediated cell death in MDA-MB-468 cells, Exp Cell Res. 346(2):224-32.
Claims (15)
- 前記の軸索もしくは神経線維を含む神経または組織が対象者の中にある、請求項1に記載の使用のための医薬組成物。
- 神経障害性、炎症性、手術後の、外傷誘導性、内臓膨張誘導性、神経変性、癌誘導性または組織変性誘導性の、痛みあるいは知覚不全の治療のための、請求項2に記載の使用のための医薬組成物。
- 対象者がアミノエステルおよび/またはアミノアミド局所麻酔薬への抵抗性あるいはアレルギーを有する、請求項2に記載の使用のための医薬組成物。
- 対象者が保持された運動機能のあるレベルを必要とする、請求項2に記載の使用のための医薬組成物。
- 医薬組成物が歯科処置に優先してまたは陣痛の間に用いられる、請求項2に記載の使用のための医薬組成物。
- 目の外傷、眼科手術、目のびらんまたはドライアイ症に関連する痛みの治療のための、請求項2に記載の使用のための医薬組成物。
- 開放創、外傷、熱傷、褥瘡または表皮水疱症(EB)に関連する痛みの治療のための、請求項2に記載の使用のための医薬組成物。
- 対象者が手術中の洗浄を受けている、請求項2に記載の使用のための医薬組成物。
- 前記使用が、任意にアミノエステルまたはアミノアミドである第二の麻酔薬を投与することをさらに含み、ここで、アミノエステルはベンゾカイン、クロロプロカイン、コカイン、シクロメチカイン、ジメソカイン/ラロカイン、ピペロカイン、プロポキシカイン、プロカイン(ノボカイン)、プロパラカインおよびテトラカイン(アメソカイン)からなる群から任意に選択され、アミノアミドはアルチカイン、ブピバカイン、シンコカイン(ジブカイン)、エチドカイン、レボブピバカイン、リドカイン(リグノカイン)、メピバカイン、プリロカイン、ロピバカインおよびトリメカインからなる群から任意に選択される、請求項2に記載の使用のための医薬組成物。
- エピネフリン、麻薬、ブプレノフィン、筋弛緩剤、非ステロイド性抗炎症剤、ヒアルロニダ-ゼ、重炭酸塩およびデキサメタゾンから選択される補助剤を投与することをさらに含む使用である、請求項2に記載の使用のための医薬組成物。
- 対象者が傷ついた感覚ニューロンを含む、軸索もしくは神経線維を含有する組織内の局所麻酔または鎮痛を必要とする、請求項2に記載の使用のための医薬組成物。
- 医薬が注射による投与あるいは目の局所投与を含む局所投与用に製剤化される、請求項2に記載の使用のための医薬組成物。
- 前記化合物又は塩が10~4000μMの濃度で含まれる、請求項1~13のいずれか1項に記載の使用のための医薬組成物。
- 前記化合物又は塩が100~1000μMの濃度で含まれる、請求項1~13のいずれか1項に記載の使用のための医薬組成物。
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US4804539A (en) | 1986-07-28 | 1989-02-14 | Liposome Technology, Inc. | Ophthalmic liposomes |
US5278151A (en) | 1987-04-02 | 1994-01-11 | Ocular Research Of Boston, Inc. | Dry eye treatment solution |
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