JP5816690B2 - テストステロン欠乏症を治療するためのテストステロン溶液 - Google Patents
テストステロン欠乏症を治療するためのテストステロン溶液 Download PDFInfo
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- JP5816690B2 JP5816690B2 JP2013524368A JP2013524368A JP5816690B2 JP 5816690 B2 JP5816690 B2 JP 5816690B2 JP 2013524368 A JP2013524368 A JP 2013524368A JP 2013524368 A JP2013524368 A JP 2013524368A JP 5816690 B2 JP5816690 B2 JP 5816690B2
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- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- XIMSTDAFGWROBF-UHFFFAOYSA-N oxathiazine 2-oxide Chemical class O=S1OC=CC=N1 XIMSTDAFGWROBF-UHFFFAOYSA-N 0.000 description 1
- 230000004963 pathophysiological condition Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- ZPWFUIUNWDIYCJ-UHFFFAOYSA-N propan-2-yl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC(C)C ZPWFUIUNWDIYCJ-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000036299 sexual function Effects 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 230000035483 skin reaction Effects 0.000 description 1
- 231100000430 skin reaction Toxicity 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 229940098466 sublingual tablet Drugs 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
- 230000008337 systemic blood flow Effects 0.000 description 1
- 235000019640 taste Nutrition 0.000 description 1
- 229940005860 testosterone 100 mg Drugs 0.000 description 1
- 150000003515 testosterones Chemical class 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 150000004072 triols Chemical class 0.000 description 1
Classifications
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- 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
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
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Description
<例1:テストステロン 0.4%>
テストステロン 400mg
RAMEB 3.640g
エタノール 10〜25%(v/v)
水で100mLにする
100μL=400μgテストステロン
テストステロン 500mg
RAMEB 4.6g
エタノール 15%(v/v)
水で100mLにする
100μL=500μgテストステロン
テストステロン 20mg
RAMEB 182mg
エタノール 0.6mL
水 4.4mL
噴射剤 20mLまで適量
25μL=25μgテストステロン
10〜15nmol/Lのベースラインレベルを有する男性志願者において:
100μL(=500μgテストステロン)の頬側投与は、投与の30分後に20nmol/Lの増加。
2×100μL(=1000μgテストステロン)の頬側投与は、投与の30分後に38nmol/Lの増加。
<例4:テストステロン 0.8%>
テストステロン 800mg
96%エタノール 12mL
ミリスチン酸イソプロピルで100mLにする
100μL=800μgテストステロン
25μL=200μgテストステロン
テストステロン 50mg
96%エタノール 0.3mL
芳香性風味剤 200mg
サッカリン 1.25mg
ミリスチン酸イソプロピル 4.7mL
噴射剤(テトラフルオロエタンHFA134a) 20mLまで適量
50μL=125μgテストステロン
テストステロン 100mg
96%エタノール 0.6mL
芳香性風味剤 200mg
サッカリン 1.25mg
ミリスチン酸イソプロピル 4.7mL
噴射剤(テトラフルオロエタンHFA134a) 20mLまで適量
50μL=250μgテストステロン
10〜15nmol/Lのベースラインテストステロンレベルを有する男性志願者において:
100μL(=800μgテストステロン)の頬側投与は、投与の30分後に36nmol/Lの増加。
50μL(=400μgテストステロン)の頬側投与は、投与の30分後に18nmol/Lの増加。
バッカル用溶液を投与して30分後の、100μgおよび500μgのテストステロン(T)当たりの血清中テストステロンレベル(T−レベル)の増加
・口腔粘膜(頬側、舌下)で投与されるテストステロン溶液は、主成分としてテストステロンおよびRAMEBを含む17例の水溶液、および主要添加剤としてミリスチン酸イソプロピルを含む7例のテストステロン溶液とした。双方の製剤とも、やはりエタノールを15%(v/v)含めた。
・24例を適用した後の、T500μg当たりのテストステロンレベルの平均増加量は、15.7nmol/L(SD4.5nmol/L)であり、水性(平均15.2nmol/L)または非水性テストステロン製剤の投与後(平均16.7nmol/L)の平均増加量の間で統計的差異はなかった。
・血清中テストステロンレベルの平均増加量は、投与されたテストステロン用量の各0.1mgについて3.1nmol/L(SD0.9)、投与されたテストステロン用量の各0.5mgについて15.7nmol/L(SD4.6)であった。
この実験では、午前中により高いレベルを有する日内変動を模擬し、必要とされる用量およびテストステロン溶液の容積を設定して、血清中テストステロンレベルを10〜35nmol/Lの正常範囲内に調節した。
・志願者Mに、午前7:30に500μgのT(25μL×4)、ならびに午前9:30および午前11:30に375μgのT(25μL×3)の水性溶液を投与した。
・血清中ジヒドロテストステロンレベルは、抽出ラジオイムノアッセイ(Diasource)で測定した。
・テストステロン(T)レベルは、いずれの場合も、正常範囲(10〜35nmol/Lの間)内にあり、ジヒドロテストステロン(DHT)レベルも正常な生理学的範囲にある。ほぼ10%のDHT/T比は、正常範囲(0.05〜0.33)内にある。
Claims (19)
- 男性対象におけるテストステロン欠乏症を口腔粘膜投与によって治療するのに使用するためのテストステロン溶液であって、前記治療が、前記男性対象に1日に2〜10回の用量で、各用量100μg〜1000μgのテストステロンを含む前記溶液10〜500μLの各用量を、噴霧、液滴の形態でまたは投薬ペンによって、口腔粘膜投与することを含むことを特徴とするテストステロン溶液。
- 請求項1に記載のテストステロン溶液であって、各用量が、10〜250μLの前記テストステロン溶液を含むことを特徴とするテストステロン溶液。
- 請求項1または請求項2に記載のテストステロン溶液であって、0.1〜10%(w/v)の範囲のテストステロン濃度を有することを特徴とするテストステロン溶液。
- 請求項1から3のいずれか一項に記載のテストステロン溶液であって、前記治療が、前記男性対象に該対象の覚醒時に1〜4時間毎に投与することを含むことを特徴とするテストステロン溶液。
- 請求項1から4のいずれか一項に記載のテストステロン溶液であって、前記治療が、1日に4〜10回用量の前記テストステロン溶液を投与することを含むことを特徴とするテストステロン溶液。
- 請求項1から5のいずれか一項に記載のテストステロン溶液であって、男性対象におけるテストステロンレベルの低下の治療が、筋肉量、骨量、認知機能、***、性的能力、***形成の低下、下垂体疾患、抑うつ気分、および骨粗鬆症から選択される、不十分な内因性テストステロンレベルに関連する疾患または症状の改善、緩和または完全な抑制をもたらすことを特徴とするテストステロン溶液。
- 請求項1から6のいずれか一項に記載のテストステロン溶液であって、テストステロンおよび1.5〜2.0の範囲にある置換度を有するランダムにメチル化されたβ−シクロデキストリンの水性溶液であることを特徴とするテストステロン溶液。
- 請求項7に記載のテストステロン溶液であって、前記ランダムにメチル化されたβ−シクロデキストリンの濃度が3〜5%(w/v)の範囲にあることを特徴とするテストステロン溶液。
- 請求項7または8に記載のテストステロン溶液であって、10〜25%(v/v)のエタノールをさらに含むことを特徴とするテストステロン溶液。
- 請求項1から6のいずれか一項に記載のテストステロン溶液であって、0〜35%(v/v)のC2〜C5アルコールおよびC8〜C22脂肪酸とC2〜C6アルコールとのエステルを含む非水性溶液であることを特徴とするテストステロン溶液。
- 請求項10に記載のテストステロン溶液であって、前記C8〜C22脂肪酸とC2〜C6アルコールとのエステルがミリスチン酸イソプロピルであり、前記C2〜C5アルコールがエタノールであることを特徴とするテストステロン溶液。
- 請求項10または11に記載のテストステロン溶液であって、前記非水性溶液が、10〜25%(v/v)のエタノールを含むことを特徴とするテストステロン溶液。
- 請求項10または11に記載のテストステロン溶液であって、エタノールとミリスチン酸イソプロピルとの容積比が、25:75であることを特徴とするテストステロン溶液。
- 請求項10または11に記載のテストステロン溶液であって、10〜25%(v/v)のエタノールおよび90〜75%(v/v)のミリスチン酸イソプロピル、加えて他の任意選択の添加剤を全体が100%(v/v)となるように含むことを特徴とするテストステロン溶液。
- 請求項1に記載のテストステロン溶液であって、10〜25%(v/v)のエタノール、0.1〜1%(w/v)のテストステロン、および1.5〜2.0の範囲にある置換度を有する、3〜5%のランダムにメチル化されたβ−シクロデキストリン、および水を含むことを特徴とするテストステロン溶液。
- 請求項1に記載のテストステロン溶液であって、0.1〜1%(w/v)のテストステロン、10〜35%(v/v)のエタノール、およびミリスチン酸イソプロピルを含むことを特徴とするテストステロン溶液。
- 請求項16に記載のテストステロン溶液であって、10〜25%(v/v)のエタノールを含むことを特徴とするテストステロン溶液。
- 請求項16に記載のテストステロン溶液であって、10〜25%(v/v)のエタノールおよび90〜75%(v/v)のミリスチン酸イソプロピル、加えて他の任意選択の添加剤を全体が100%(v/v)となるように含むことを特徴とするテストステロン溶液。
- 請求項1から18のいずれか一項に記載のテストステロン溶液であって、各用量で投与されるテストステロン量が、正常で健康な男性におけるテストステロンレベルの概日リズムを模擬するために、生じるテストステロンレベルが午後よりも午前の時間により高くなるように前以て決定されることを特徴とするテストステロン溶液。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB1013701.6A GB2482868A (en) | 2010-08-16 | 2010-08-16 | A testosterone liquid spray formulation for oromucosal administration |
GB1013701.6 | 2010-08-16 | ||
PCT/EP2011/004031 WO2012022446A1 (en) | 2010-08-16 | 2011-08-09 | Testosterone solutions for the treatment of testosterone deficiency |
Publications (3)
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JP2013534228A JP2013534228A (ja) | 2013-09-02 |
JP2013534228A5 JP2013534228A5 (ja) | 2014-01-16 |
JP5816690B2 true JP5816690B2 (ja) | 2015-11-18 |
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JP2013524368A Expired - Fee Related JP5816690B2 (ja) | 2010-08-16 | 2011-08-09 | テストステロン欠乏症を治療するためのテストステロン溶液 |
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US (1) | US9498436B2 (ja) |
EP (1) | EP2605778B1 (ja) |
JP (1) | JP5816690B2 (ja) |
CN (1) | CN103118684A (ja) |
AU (1) | AU2011291075B2 (ja) |
BR (1) | BR112013003471A2 (ja) |
CA (1) | CA2807405A1 (ja) |
DK (1) | DK2605778T3 (ja) |
ES (1) | ES2539582T3 (ja) |
GB (1) | GB2482868A (ja) |
WO (1) | WO2012022446A1 (ja) |
ZA (1) | ZA201300858B (ja) |
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DE102010038259B4 (de) | 2010-10-19 | 2013-02-07 | 4Jet Sales + Service Gmbh | Verfahren und Vorrichtung zum Gravieren eines flexiblen Bands |
US20130040923A1 (en) | 2011-05-13 | 2013-02-14 | Trimel Pharmaceuticals Corporation | Intranasal lower dosage strength testosterone gel formulations and use thereof for treating anorgasmia or hypoactive sexual desire disorder |
US9757388B2 (en) | 2011-05-13 | 2017-09-12 | Acerus Pharmaceuticals Srl | Intranasal methods of treating women for anorgasmia with 0.6% and 0.72% testosterone gels |
US20130045958A1 (en) | 2011-05-13 | 2013-02-21 | Trimel Pharmaceuticals Corporation | Intranasal 0.15% and 0.24% testosterone gel formulations and use thereof for treating anorgasmia or hypoactive sexual desire disorder |
WO2014083432A2 (en) * | 2012-11-14 | 2014-06-05 | Trimel Biopharma Srl | Female intranasal lower dosage strength testosterone gel formulations and use thereof for treating anorgasmia or hypoactive sexual desire disorder |
US11744838B2 (en) | 2013-03-15 | 2023-09-05 | Acerus Biopharma Inc. | Methods of treating hypogonadism with transnasal testosterone bio-adhesive gel formulations in male with allergic rhinitis, and methods for preventing an allergic rhinitis event |
ITUB20161027A1 (it) | 2016-02-24 | 2017-08-24 | Altergon Sa | Preparazioni farmaceutiche oromucosali ad elevata biodisponibilita’ a base di ciclodestrina e sucralosio |
SG11202007303YA (en) * | 2018-02-02 | 2020-08-28 | Aytu Bioscience Inc | Methods of testosterone therapy |
CN108524485A (zh) * | 2018-02-24 | 2018-09-14 | 中山大学 | 一种猴睾酮缺乏模型的建立方法 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4596795A (en) * | 1984-04-25 | 1986-06-24 | The United States Of America As Represented By The Secretary, Dept. Of Health & Human Services | Administration of sex hormones in the form of hydrophilic cyclodextrin derivatives |
EP0381747A4 (en) * | 1988-08-15 | 1991-09-11 | American Maize-Products Company | Water soluble branched beta cyclodextrin steroid complex |
PT910339E (pt) | 1996-04-12 | 2005-05-31 | Novadel Pharma Inc | Aerossol polar bucal |
US5955098A (en) * | 1996-04-12 | 1999-09-21 | Flemington Pharmaceutical Corp. | Buccal non polar spray or capsule |
US20050180923A1 (en) * | 1997-10-01 | 2005-08-18 | Dugger Harry A.Iii | Buccal, polar and non-polar spray containing testosterone |
FR2784584B1 (fr) * | 1998-10-14 | 2002-09-20 | Adir | Procede de preparation d'une solution pour pulverisation nasale contenant une ou plusieurs hormones sexuelles et une cyclodextrine |
US20030027804A1 (en) * | 2001-06-27 | 2003-02-06 | Van Der Hoop Roland Gerritsen | Therapeutic combinations for the treatment of hormone deficiencies |
US7233228B2 (en) * | 2002-04-29 | 2007-06-19 | Glaxo Group Limited | Alerting system |
MXPA06003316A (es) * | 2003-10-10 | 2006-06-08 | Antares Pharma Ipl Ag | Formulacion farmaceutica transdermica para minimizar los residuos en la piel. |
DE60303854T2 (de) | 2003-11-11 | 2006-08-10 | Mattern, Udo | Nasenformulierung mit kontrollierter Freisetzung von Sexualhormonen |
EP1872774A1 (en) * | 2006-06-07 | 2008-01-02 | Familplan Consulting Ltd Oy | A pharmaceutical composition adapted for oral transmucosal administration comprising sex hormone and its use |
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US9498436B2 (en) | 2016-11-22 |
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GB201013701D0 (en) | 2010-09-29 |
WO2012022446A1 (en) | 2012-02-23 |
AU2011291075A1 (en) | 2013-03-28 |
JP2013534228A (ja) | 2013-09-02 |
CN103118684A (zh) | 2013-05-22 |
EP2605778A1 (en) | 2013-06-26 |
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