JP2022183154A - ビスホスホシンゲル製剤及びその使用 - Google Patents
ビスホスホシンゲル製剤及びその使用 Download PDFInfo
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- JP2022183154A JP2022183154A JP2022147051A JP2022147051A JP2022183154A JP 2022183154 A JP2022183154 A JP 2022183154A JP 2022147051 A JP2022147051 A JP 2022147051A JP 2022147051 A JP2022147051 A JP 2022147051A JP 2022183154 A JP2022183154 A JP 2022183154A
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Classifications
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- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
本願は、その全体において本明細書に参照により組み込まれる、2017年6月12日提出の米国仮特許出願第62/518,262号の優先権を主張する。
を有する。
を有する。
を有する。
を有する。
本開示の別の態様において、pH調整剤は、本組成物のpHを約pH3~約pH4に調整するのに十分な量で存在する。
(式中、Aは、H、アルキル、アルキル-(O-アルキル)、アリール、アルケニル、アルカノール、フェノール又はエノールであり;
式中、Qは、O、S、P-H、P-OH、P-アルキル、P-アリール、P-アシル、N-H、N-OH、N-アルキル、N-アリール、N-アシル、-CH2、-CH(OH)又はCH(O-アルキル)であり;
式中、X及びZは、アルキル又はO-アルキル末端ブロッキング基であり;
式中、Wは、H、プリン、ピリミジン又はプリンもしくはピリミジンの修飾類似体である。);又は薬学的に許容可能なその塩の構造を有する。いくつかの実施形態において、X及び/又はZはアルキル末端ブロッキング基を含み、ここでアルキル部分は直鎖、分岐鎖又は環状である。いくつかの実施形態において、アルキル部分は1~4個の炭素を有し、直鎖である。いくつかの実施形態において、X及びZは同じ化学部分を有する。いくつかの実施形態において、X及びZは異なる化学部分を有する。いくつかの実施形態において、X及びZはブチル基を含む。いくつかの実施形態において、Xはブチル基であり、Zはブタノールである。いくつかの実施形態において、Xはブタノールであり、Zはブチル基である。いくつかの実施形態において、X及び/又はZは、CH3CH2CH2CH2-、CH3CH2CH2-、CH3CH2-及びHOCH2CH2CH2CH2-からなる群から選択される構造を含む。
(式中、環Aは、遊離アミノ基が環炭素原子に連結される飽和又は部分的不飽和の何れかである安定な5~7員単環式又は7~10員二環式炭素環式又は複素環式部分であり、R1及びR2は、分岐状又は非分岐状であり得るC1-C8アルキル部分の群からそれぞれ独立して選択される。)又は薬学的に許容可能なその塩を有する。
本開示の化合物を含む今回記載のゲル製剤は、様々な活性成分及び様々な生理学的担体分子とともに製剤化し得る。本開示の化合物は、場合によっては、標的細胞への侵入能を高める分子と複合化され得る。このような分子の例としては、炭水化物、ポリアミン、アミノ酸、ペプチド、脂質及び細菌の増殖に不可欠な分子が挙げられるが限定されない。
今回記載される製剤はまた、実験室の培養物、消耗品(食品又は飲料調製品)、医療機器、病院の装置又は工業プロセスの微生物(例えば細菌、真菌、原虫又はウイルス)汚染に対抗するのに有効であることも企図される。
本開示のゲル製剤は、処方薬(例えばベンゾマイシン)及び市販薬(例えば、サリチル酸、過酸化ベンゾイルなど)の両方とともに他の抗生剤を含む局所抗生物質製剤として有用であり得る。疾患の治療的処置において使用される場合、本開示の化合物及び別の活性成分を含有するゲル製剤の適切な投与量は、いくつかの十分に確立された方法論の何れかによって決定され得る。例えば、動物実験は、体重1キログラムあたりの生物活性剤の最大耐容量又はMTDを決定するために一般的に使用される。一般に、試験した動物種の少なくとも1つは哺乳動物である。当業者は、有効性のために用量を定期的に外挿し、ヒトを含む他の種への毒性を回避する。さらに、感染の重症度及び宿主の体格又は種などの要因に応じて、治療投与量を変更することもできる。
本開示の化合物の一部はヌクレオシドの天然構造に基づくので、本開示の化合物を含む製剤は効率的な抗ウイルス活性を保持し得る。
本開示の化合物を含むゲル製剤は、従来の抗菌剤と併用することもできる。活性成分のさらなる活性は、より効果的な製剤を提供し得、微生物が標的とされる複数の機序をもたらし得る。別の活性剤と混合して本開示の化合物を含有する医薬組成物は、従来の医薬配合技術に従って調製し得る。
本開示の化合物を含有する本明細書中に記載のゲル製剤は、消毒剤として、及び静菌性又は殺生物性を有する調製物としての用途も見出し得る。本開示の消毒剤ゲル製剤はまた、静菌性及び/又は殺生物性がある他の活性成分も含有し得る。例えば、消毒剤ゲルは、ジメチルベンジルドデシルアンモニウムクロリド、ジメチルベンジルデシルアンモニウムクロリド、ジメチルベンジルデシルアンモニウムブロミド及びジメチルベンジルオクチルアンモニウムクロリド(dimethylbenzylloctylammonium chloride)などの適切な濃度の四級アンモニウム化合物とともに本開示の化合物を含有し得る。
本開示に関連する例を以下に記載する。殆どの場合、代替技術を使用し得る。例は例示であることを意図するものであり、特許請求の範囲で示されるような本発明の範囲を限定又は制限するものではない。
以下の段階は、100gスケールで遊離酸としてNu-3の溶液を使用してセルロースゲルを調製するために使用される。
1.水の一部にNu-3を添加し、均一になるまで混合する。
2.塩化ナトリウムを添加し、均一になるまで混合する。
3.4%NaOHを使用してpHを1.5(1.4~1.6の許容範囲)に調整する。
4.残りの水を添加し、均一になるまで混合する。
5.ヒドロキシエチルセルロース粉末(Natrosol 250 HHX PH,Ashland)を混合プロペラの渦にゆっくりと添加する。
6.ポリマーゲルが透明になるまで(~45-60分)混合を継続する。
以下の段階は、100gスケールで二ナトリウム塩としてNu-3の溶液を使用してFAゲルを調製するために使用される。
1.水の一部にNu-3を添加し、均一になるまで混合する。
2.10%HClを使用してpHを1.5(1.4~1.6が許容範囲)に調整する。
3.残りの水を添加し、均一になるまで混合する。
4.別個の容器中で、セトステアリルアルコール(Crodacol CS 50 NF,Croda)及びセテアレス-20(Cetomacrogol 1000 NF,Croda)を組み合わせ、混合しながらホットプレート上で~60℃に加熱して、脂肪アルコール及び界面活性剤を融解させる。~60℃で保持する。
5.プロペラミキサーで混合しながら、ホットプレート上で~60℃にAPI溶液を加熱する。
6.プロペラミキサーで混合しながら、脂肪アルコール/界面活性剤混合物をAPI溶液に添加する。プロペラミキサーを取り外し、容器を熱源から取り外し、高せん断混合を開始する。
7.ゲルが冷えて濃厚になるので、高せん断混合を継続する(~45-50℃)。
8.ゲルが濃厚になりすぎてホモジナイザーで混合できない場合は、高せん断混合を停止し、ゲルが35~40℃)に達するまでプロペラミキサーで混合を継続する。
表1のクロマトグラフィー条件を使用して、この例に対してNu-3製剤をアッセイする。
0.05~0.4mg/mLのNu-3溶液を使用して、直線性を評価する。mg/mLに対するピーク面積についての相関係数は0.9994の値を有する。0.2mg/mL標準液を繰り返し注入した場合の%相対標準偏差(RSD)は<1.0%である。
評価のために3種類のビヒクルゲルを調製する。式(I)の化合物の存在を模倣するためにリン酸ナトリウムを使用し、抗菌防腐剤としてベンジルアルコールを使用する。それらの組成を表2でまとめる。
ゲル2及び3は、それらの優れた物理的特性ゆえに5%w/wでNu-3を用いた製剤に対して選択される。Nu-3の最適な活性を確保するために、製剤のpHを1.5の目標値まで低下させる。
このゲルに対する組成を表3で示す。
5%Nu-3セルロースゲルの初期に対する結果及び安定性の結果を表4でまとめる。
保管時に、セルロースNu-3ゲルの粘度は温度とともに著しく低下する。これはおそらく、ポリマー中のセルロースの加水分解によるものである。しかし、40℃で1か月保管した後のアッセイ及びpHに顕著な変化はない。
これらのゲルに対する組成を表5で示す。
配合中、FA Gel1は濃厚にならない。
FA Gel 2の場合、セトステアリルアルコールレベルが4.0から7.25%w/wに上昇する。これにより、ビヒクル及び5%Nu-3製剤に対するゲル粘度が上昇する。Nu-3 FA Gel 2に対する安定性データを表6でまとめる。
FA Gel 2に対する、アッセイ、外観及びpHは、25又は40℃で1か月後に顕著な変化を示さない。保管時に粘度が僅かに上昇するが、これは脂肪アルコールゲルでは珍しいことではない。それらの粘度は、1~3か月の保管後に横ばいになる傾向がある。
これらのゲルに対する組成を表7で示し、安定性の結果を表8で示す。
10~20%Nu-3入りのFAゲルに対する、アッセイ、外観及びpHは、25又は40℃で1か月後に顕著な変化を示さない。保管時に粘度が僅かに上昇するが、これは脂肪アルコールゲルでは珍しいことではない。それらの粘度は、1~3か月の保管後に横ばいになる傾向がある。
動物及び畜産
Charles River Laboratoriesから注文された雌SKH1マウスは、飼育条件に順応させ、Animal Use Protocol(AUP)番号TP-18に従って取り扱う。動物は、細菌負荷試験前に最短で24時間順応させ、実験の第0日に6~8週齢である。健康とみなされる動物のみをこの研究に含める。動物には、照射したTeklad Global Rodent Diet 2918及び水を自由に与える。マウスは、1時間あたり100回の完全な空気交換でバブル環境にH.E.P.A.フィルター処理空気を提供するbioBubble(登録商標)クリーンルーム内に、照射済みTeklad 1/8”コーンコブベッディング7902を備えた静置ケージに収容する。全ての処置及び感染負荷は、BSL2手術スイートで実施する。74°+4°Fの温度範囲及び30~70%の湿度範囲に環境を制御する。処置群はケージカードによって識別する。この実験で実施される全ての手順は、National Institutes of Healthの法律、規制、ガイドラインに準拠し、TransPharm Animal Care and Use Committeeの承認を得て実施される。
この研究で使用する細菌株は、Barry Kreiswirth研究室(Public Health Research Institute Center,New Jersey Medical School)から調達したメチシリン耐性スタフィロコッカス・アウレウス(Staphylococcus aureus)株USA300(TPPS 1056)である。
感染直前の第0日に、イソフルラン誘導チャンバーを使用して各マウスに麻酔をかけ、皮膚の最外表皮層を除去するために、背部にNexcare(商標)(3M)外科用テープを7~10回貼付し、除去した。
生物は、5%ヒツジ血液細胞を補充したトリプチケース大豆寒天プレート上で、周囲大気中、37℃で一晩増殖させた。負荷日(第0日)に、培養物を無菌的に拭い取り、TSBの培養チューブに移した。培養物を光学密度が600nmでおよそ0.65に達するまで37℃の水浴で増殖させ、およそ109コロニー形成単位(CFU)/mLの未希釈細菌濃度を得た。次いで、培養物を希釈して、100μLの体積でマウスあたり6.0 log10 CFUの負荷接種物を与える。
接種材料カウントは接種前に光学密度により推定し、接種後に希釈及び逆算により確認する。
Nu-3の10%(100mg/mL)溶液を脂肪アルコールに基づくゲル中で調製する。塩酸を使用して溶液をpH1.5に調整する。
研究に基づいて指定時点でマウスを回収する。各時点で各グループから4匹のマウスを回収する。
処置に関連する何らかの急性有害事象を示したマウスはいなかった。循環系又は深部組織への感染の浸透に起因し得る感染により死亡したか又は病的状態の兆候を示したマウスはなかった。表在性の細菌感染を受けたマウスについて予想されるもの以上の有害な兆候を示す群はなかった。
Claims (55)
- Nu-2、Nu-3、Nu-4、Nu-5及びNu-8又は薬学的に許容可能なその塩、又はそれらの何らかの組み合わせからなる群から選択されるビスホスホシンと、
脂肪アルコール増粘剤と、
非イオン性ポリマー乳化剤と、
を含む、ゲル製剤。 - ビスホスホシンが、Nu-3又は薬学的に許容可能なその塩である、請求項1に記載の製剤。
- 約pH1~約pH5のpHを有する、請求項1に記載の製剤。
- 約pH1.5~約pH4のpHを有する、請求項1に記載の製剤。
- 約pH3~約pH4のpHを有する、請求項1に記載の製剤。
- ビスホスホシンが、製剤中に約1%~約20%(重量/重量)の量で存在する、請求項1に記載の製剤。
- ビスホスホシンが、製剤中に約5%~約15%(重量/重量)の量で存在する、請求項6に記載の製剤。
- ビスホスホシンが、製剤中に約30%~約50%(重量/重量)の量で存在する、請求項1に記載の製剤。
- 脂肪アルコール増粘剤が、製剤中に約1%~約50%(重量/重量)の量で存在する、請求項1に記載の製剤。
- 脂肪アルコール増粘剤が、製剤中に約1%~約20%(重量/重量)の量で存在する、請求項1に記載の製剤。
- 脂肪アルコール増粘剤が、製剤中に約1%~約10%(重量/重量)の量で存在する、請求項1に記載の製剤。
- 非イオン性ポリマー乳化剤が、製剤中に約0.25%~約15%(重量/重量)の量で存在する、請求項1に記載の製剤。
- 非イオン性ポリマー乳化剤が、製剤中に約0.5%~約5%(重量/重量)の量で存在する、請求項1に記載の製剤。
- 水、グリセロール、マンニトール、生理食塩水及びリン酸緩衝食塩水からなる群から選択される希釈剤をさらに含む、請求項1に記載の製剤。
- 希釈剤が水である、請求項14に記載の製剤。
- 水が、製剤中に約65%~約97.5%(重量/重量)の量で存在する、請求項15に記載の製剤。
- 脂肪アルコール増粘剤が、セチルアルコール、ラウリルアルコール、ステアリルアルコール、セトステアリルアルコール、ミリスチルアルコール、ドコサノールアルコール及びオレイルアルコールからなる群から選択される、請求項1に記載の製剤。
- 脂肪アルコール増粘剤がセトステアリルアルコールである、請求項17に記載の製剤。
- セトステアリルアルコールが、製剤中に約2%~約10%(w/w)の量で存在する、請求項18に記載の製剤。
- 非イオン性ポリマーが、セテス-20、ステアレス-20及びセテアレス-20からなる群から選択される、請求項1に記載の製剤。
- 非イオン性ポリマー乳化剤がセテアレス20である、請求項20に記載の製剤。
- セテアレス-20が、製剤中に約0.5%(w/w)より多い量で存在する、請求項21に記載の製剤。
- セテアレス-20が、製剤中に約0.5%~約5%(w/w)の量で存在する、請求項21に記載の製剤。
- 局所投与に適合している、請求項1に記載の製剤。
- 請求項1に記載の製剤の有効量を患者に投与することを含む、感染症の処置を必要とする患者において感染症を処置する方法。
- 感染症が糖尿病性足潰瘍の感染である、請求項25に記載の方法。
- 感染症が熱傷創の感染である、請求項25に記載の方法。
- 感染症が併発(complicated)静脈下肢潰瘍の感染である、請求項25に記載の方法。
- 感染症が外耳炎感染である、請求項25に記載の方法。
- 請求項1に記載の製剤の有効量を患者に投与することを含む、尋常性ざ瘡の処置を必要とする患者において尋常性ざ瘡を処置する方法。
- 請求項1に記載の製剤の有効量を患者に投与することを含む、爪真菌症の処置を必要とする患者において爪真菌症を処置する方法。
- 請求項1に記載の製剤の有効量を患者に投与することを含む、結膜炎の処置を必要とする患者において結膜炎を処置する方法。
- 請求項1に記載の製剤の有効量を患者に投与することを含む、口腔粘膜炎の処置を必要とする患者において口腔粘膜炎を処置する方法。
- 少なくとも1つのさらなる活性成分が患者に投与される、請求項25に記載の方法。
- 患者がヒトである、請求項25記載の方法。
- 治療での使用のための、請求項1に記載の製剤。
- 感染症の処置での使用のための、請求項1に記載の製剤。
- 糖尿病性足潰瘍の感染症の処置での使用のための、請求項1に記載の製剤。
- 熱傷創の処置での感染症の処置での使用のための、請求項1に記載の製剤。
- 併発(complicated)静脈下肢潰瘍の感染症の処置での使用のための、請求項1に記載の製剤。
- 尋常性ざ瘡の処置での使用のための、請求項1に記載の製剤。
- 外耳炎の処置での使用のための、請求項1に記載の製剤。
- 爪真菌症の処置での使用のための、請求項1に記載の製剤。
- 結膜炎の処置での使用のための、請求項1に記載の製剤。
- 口腔粘膜炎の処置での使用のための、請求項1に記載の製剤。
- 薬剤の製造での使用のための、請求項1に記載の製剤。
- 薬剤が、熱傷創における感染症を処置するためのものである、請求項46に記載の使用。
- 薬剤が、糖尿病性足潰瘍での感染症を処置するためのものである、請求項46に記載の使用。
- 薬剤が、併発(complicated)静脈下肢潰瘍での感染症を処置するためのものである、請求項46に記載の使用。
- 薬剤が、尋常性ざ瘡を処置するためのものである、請求項46に記載の使用。
- 薬剤が、外耳炎を処置するためのものである、請求項46に記載の使用。
- 薬剤が、爪真菌症を処置するためのものである、請求項46に記載の使用。
- 薬剤が、結膜炎を処置するためのものである、請求項46に記載の使用。
- 薬剤が、口腔粘膜炎を処置するためのものである、請求項46に記載の使用。
- 薬剤が局所投与に適合される、請求項46に記載の使用。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
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US201762518262P | 2017-06-12 | 2017-06-12 | |
US62/518,262 | 2017-06-12 | ||
PCT/US2018/037151 WO2018231863A1 (en) | 2017-06-12 | 2018-06-12 | Bisphosphocin gel formulations and uses thereof |
JP2019567981A JP7148994B2 (ja) | 2017-06-12 | 2018-06-12 | ビスホスホシンゲル製剤及びその使用 |
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US8492369B2 (en) | 2010-04-12 | 2013-07-23 | Clarus Therapeutics Inc | Oral testosterone ester formulations and methods of treating testosterone deficiency comprising same |
DK2985026T3 (da) | 2005-04-15 | 2022-10-31 | Clarus Therapeutics Inc | Farmaceutiske leveringssystemer til hydrofobe lægemidler og sammensætninger dermed |
US11377468B2 (en) | 2017-03-10 | 2022-07-05 | Lakewood Amedex, Inc. | Antimicrobial compounds, compositions, and uses thereof |
US11795192B2 (en) | 2017-03-10 | 2023-10-24 | Lakewood Amedex, Inc. | Antimicrobial compounds, compositions, and uses thereof |
BR122021004504B1 (pt) * | 2017-03-10 | 2022-08-23 | Lakewood Amedex, Inc. | Uso de um composto antimicrobiano |
EP3866810A4 (en) * | 2018-10-17 | 2022-07-27 | Lakewood Amedex, Inc. | METHODS AND COMPOSITIONS FOR THE TREATMENT OF ORAL MUCOSITIS |
US20230092578A1 (en) * | 2021-07-22 | 2023-03-23 | Lakewood Amedex, Inc. | Methods for preparing bisphosphocins |
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US4105782A (en) | 1975-03-07 | 1978-08-08 | Yu Ruey J | Treatment of acne and dandruff |
SE8004580L (sv) | 1980-06-19 | 1981-12-20 | Draco Ab | Farmaceutisk beredning |
KR830005852A (ko) * | 1980-07-18 | 1983-09-14 | 미첼 페터 잭슨 | 피부와 점막의 비루스 감염치료에 적합한 국소치료제의 제조방법 |
US4421769A (en) * | 1981-09-29 | 1983-12-20 | The Procter & Gamble Company | Skin conditioning composition |
DE3542516A1 (de) | 1985-12-02 | 1987-06-04 | Henkel Kgaa | Desinfektionsmittel |
DE3731255A1 (de) * | 1987-09-17 | 1989-04-06 | Boehringer Ingelheim Int | Stabilisierung von therapeutisch wirksamen proteinen in pharmazeutischen zubereitungen |
US5153230A (en) | 1989-10-06 | 1992-10-06 | Perfective Cosmetics, Inc. | Topical skin cream composition |
US5167950A (en) | 1991-03-28 | 1992-12-01 | S. C. Johnson & Son | High alcohol content aerosol antimicrobial mousse |
US5208015A (en) * | 1991-07-23 | 1993-05-04 | Bristol-Myers Squibb Company | Topical anti-fungal agents having anti-inflammatory activity |
DE4333385C2 (de) | 1993-09-30 | 1997-01-30 | Friedrich A Spruegel | Flächendesinfektions- und Reinigungsmittel |
CZ267396A3 (en) * | 1994-03-11 | 1997-03-12 | Procter & Gamble | HYDROLYTIC STABLE COSMETIC, PREPARATION WITH LOW pH VALUE CONTAINING ACID ACTIVE SUBSTANCES |
FR2718022B1 (fr) | 1994-04-01 | 1996-04-26 | Roussel Uclaf | Compositions cosmétiques ou dermatologiques et leur préparation. |
FR2722102B1 (fr) * | 1994-07-11 | 1996-08-23 | Cird Galderma | Utilisation de particules creuses deformables dans une composition cosmetique et/ou dermatologique, contenant des matieres grasses |
US5843998A (en) | 1997-06-30 | 1998-12-01 | Song; Jin | Skin blemish treatment |
US6211162B1 (en) | 1998-12-30 | 2001-04-03 | Oligos Etc. Inc. | Pulmonary delivery of protonated/acidified nucleic acids |
US6627215B1 (en) | 1998-12-30 | 2003-09-30 | Oligos Etc. Inc. | Devices for improved wound management |
US20020032164A1 (en) | 1998-12-30 | 2002-03-14 | Dale Roderic M. K. | Antimicrobial compounds and methods for their use |
US6211349B1 (en) | 1998-12-30 | 2001-04-03 | Oligos Etc., Inc. | Protonated/acidified nucleic acids and methods of use |
US7868162B2 (en) * | 1998-12-30 | 2011-01-11 | Lakewood-Amedex, Inc. | Antimicrobial and antiviral compounds and methods for their use |
US6156294A (en) * | 1999-11-28 | 2000-12-05 | Scientific Development And Research, Inc. | Composition and method for treatment of otitis media |
WO2003032909A2 (en) * | 2001-10-18 | 2003-04-24 | Ilex Products, Inc. | Methods of treating skin with diphosphonate derivatives |
JP5711867B2 (ja) * | 2003-04-24 | 2015-05-07 | ガルデルマ・ソシエテ・アノニム | 皮膚科学的疾患の治療のためのアイバメクチンの使用 |
CN1687100A (zh) * | 2005-04-05 | 2005-10-26 | 奥林格斯技术有限公司 | 修饰性核苷酸及其用途 |
EP2149375A1 (en) | 2008-07-28 | 2010-02-03 | Despharma Kft. | Compositions for the treatment of dermatological diseases, and uses thereof |
WO2015075406A1 (en) | 2013-11-19 | 2015-05-28 | Lipopeptide Ab | New treatment of chronic ulcers |
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JP7148994B2 (ja) | 2022-10-06 |
US20180353529A1 (en) | 2018-12-13 |
EP3638251A4 (en) | 2021-03-10 |
JP2020523322A (ja) | 2020-08-06 |
AU2018282905A1 (en) | 2019-12-19 |
CN110753549A (zh) | 2020-02-04 |
EP4241769A2 (en) | 2023-09-13 |
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