JP2009514777A - 凍結乾燥fsh/lh製剤 - Google Patents
凍結乾燥fsh/lh製剤 Download PDFInfo
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- JP2009514777A JP2009514777A JP2006516157A JP2006516157A JP2009514777A JP 2009514777 A JP2009514777 A JP 2009514777A JP 2006516157 A JP2006516157 A JP 2006516157A JP 2006516157 A JP2006516157 A JP 2006516157A JP 2009514777 A JP2009514777 A JP 2009514777A
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- fsh
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- lyophilized formulation
- tween
- hormone
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- 235000010233 benzoic acid Nutrition 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 108010066058 beta Subunit Luteinizing Hormone Proteins 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- KDQPSPMLNJTZAL-UHFFFAOYSA-L disodium hydrogenphosphate dihydrate Chemical compound O.O.[Na+].[Na+].OP([O-])([O-])=O KDQPSPMLNJTZAL-UHFFFAOYSA-L 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
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- 108010006578 follitropin alfa Proteins 0.000 description 1
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- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
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- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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- 150000002772 monosaccharides Chemical class 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
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- 239000000825 pharmaceutical preparation Substances 0.000 description 1
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- ORMNNUPLFAPCFD-DVLYDCSHSA-M phenethicillin potassium Chemical compound [K+].N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C([O-])=O)=O)C(=O)C(C)OC1=CC=CC=C1 ORMNNUPLFAPCFD-DVLYDCSHSA-M 0.000 description 1
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- 230000002028 premature Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 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
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- 235000019259 sodium dehydroacetate Nutrition 0.000 description 1
- 229940079839 sodium dehydroacetate Drugs 0.000 description 1
- BBMHARZCALWXSL-UHFFFAOYSA-M sodium dihydrogenphosphate monohydrate Chemical compound O.[Na+].OP(O)([O-])=O BBMHARZCALWXSL-UHFFFAOYSA-M 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- DSOWAKKSGYUMTF-GZOLSCHFSA-M sodium;(1e)-1-(6-methyl-2,4-dioxopyran-3-ylidene)ethanolate Chemical compound [Na+].C\C([O-])=C1/C(=O)OC(C)=CC1=O DSOWAKKSGYUMTF-GZOLSCHFSA-M 0.000 description 1
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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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/24—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- 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
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- 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
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
Abstract
Description
−スクロースエキストラピュアMerckコード番号1.07653
−リン酸二水素ナトリウム一水和物(以下、NaH2PO4 H20として示す)Merckコード番号1.06346
−リン酸水素二ナトリウム二水和物(以下、Na2HPO4 2H20として示す)Merckコード番号1.06580
−Tween 20Merckコード番号1822184
−L−メチオニン Rexim
−注射用水
−オルトリン酸85%エキストラピュアMerckコード番号1.00563
−オルトリン酸(約17%w/w)溶液
−水酸化ナトリウムペレットエキストラピュアMerckコード番号1.06498
以下の組成を有する凍結乾燥製剤Aを調製した:
製剤A
FSH μg 12.0(156I.U.)
LH μg 3.7(92I.U.)
スクロース mg 30.0
NaH2PO4 H20 mg 0.45
Na2HPO4 2H20 mg 1.11
Tween 20 mg 0.05
L−メチオニン mg 0.1
−風袋を計った容器にWFI、リン酸水素二ナトリウム二水和物、リン酸二水素ナトリウム一水和物、スクロース、5%のTween20及びL−メチオニンを添加し、そして完全に溶解するまで10分間攪拌する。
−pHを調べ、そして最終的にそれを10%NaOH又は希釈したH3PO4でpH7.00±0.2に修正する。
−FSH及びLHを上記の調製した混合物に添加し、そして得られた溶液を10分間穏やかに攪拌する。
−再びpHを調べ、そして最終的にそれを10%NaOH又は希釈したH3PO4でpH7.0±0.1に修正する。
−15g/cm2以上の濾過率を有する0.22μmのDurapore膜を用い、1.5atm(151987.5Pa)の窒素ガス流のもと溶液を濾過する。
−前記溶液を予め滅菌したフラスコに回収する。
−濾過した溶液をガラス容器に充填し、ストッパーで封をし、そして充填したバイアルをステンレス鋼のトレイに置く。
−前記トレイを凍結乾燥機に載せ、そして以下の凍結乾燥サイクルを用いて生成物を凍結乾燥する:
・+4℃で約20分間平衡化する。
・棚の温度を−25℃にし、そして2時間維持する。
・棚の温度を−15℃にし、そして1時間維持する。
・棚の温度を−45℃にし、そして3時間維持する。
・濃縮機の温度を−65℃にする。
・チャンバーを真空状態にする。
・真空が7x10-2mBarの値に達したら、棚の温度を−10℃にまで上昇させ、そして14時間維持する。
・棚の温度を8時間で+35℃にまで上昇させ、そしてこのサイクルの最後まで維持する(14時間)。
・真空状態を中断して乾燥窒素をチャンバー内に封入する。
・凍結乾燥機の自動システムにより蓋をする。
・蓋をしたバイアルを適切なフリップオフキャップで密封する。
・FSHのin vivoアッセイ:製剤は、FSH活性についてSteelman-Pohley卵巣増量バイオアッセイを用いて試験した。
・LHのin vivoアッセイ:製剤は、LH活性についてラット精嚢増量バイオアッセイを用いて試験した。
・酸化型アルファサブユニットのアッセイ:酸化型アルファサブユニットのパーセンテージは、逆相HPLC(RP−HPLC)法で測定した。
・遊離サブユニット(rFSH+rLH)の評価:遊離サブユニットのパーセンテージをSDS−PAGEで評価した。
・凝集物の評価:凝集物のパーセンテージは、遊離サブユニットの評価について上述したようにSDS−PAGEにより評価した。
配列番号1:ヒト糖タンパク質α−サブユニット
配列番号2:hFSHβ−サブユニット
配列番号3:hFSHβ−サブユニット変異体1
配列番号4:hFSHβ−サブユニット変異体2
配列番号5:hFSHβ−サブユニット変異体3
配列番号6:hLHβ−サブユニット
Claims (23)
- 卵胞刺激ホルモン(FSH)又はその変異体並びに黄体形成ホルモン(LH)又はその変異体、並びにTween 20(ポリオキシエチレン(20)ソルビタンモノラウレート)、Tween 40(ポリオキシエチレン(20)ソルビタンモノパルミテート)、Tween 80(ポリオキシエチレン(20)ソルビタンモノオレエート)を含むポリソルベートから選択される界面活性剤、を含んで成る凍結乾燥製剤。
- 界面活性剤がTween 20である、請求項1に記載の凍結乾燥製剤。
- 卵胞刺激ホルモンがヒト卵胞刺激ホルモンであり、そして/あるいは黄体形成ホルモン(LH)がヒト黄体形成ホルモン(LH)である、請求項1又は2に記載の凍結乾燥製剤。
- 卵胞刺激ホルモンが尿のヒト卵胞刺激ホルモンであり、そして/あるいは黄体形成ホルモン(LH)が尿のヒト黄体形成ホルモン(LH)である、請求項3に記載の凍結乾燥製剤。
- 卵胞刺激ホルモンが組換えヒト卵胞刺激ホルモンであり、そして/あるいは黄体形成ホルモン(LH)が組換えヒト黄体形成ホルモン(LH)である、請求項1〜3のいずれか1項に記載の凍結乾燥製剤。
- 卵胞刺激ホルモン(FSH)が全製剤1mg当たり約0.1〜10μgの濃度(w/w)で存在する、請求項1〜5のいずれか1項に記載の凍結乾燥製剤。
- 卵胞刺激ホルモン(FSH)が全製剤1mg当たり約0.3〜5μgの濃度で存在する、請求項6に記載の凍結乾燥製剤。
- 卵胞刺激ホルモン(FSH)が全製剤1mg当たり約0.37〜2μgの濃度で存在する、請求項7に記載の凍結乾燥製剤。
- 黄体形成ホルモン(LH)が全製剤1mg当たり約0.1〜3μgの濃度で存在する、請求項1〜8のいずれか1項に記載の凍結乾燥製剤。
- 黄体形成ホルモン(LH)が全製剤1mg当たり約0.1〜1μgの濃度で存在する、請求項9に記載の凍結乾燥製剤。
- 黄体形成ホルモン(LH)が全製剤1mg当たり約0.1〜0.6μgの濃度で存在する、請求項10に記載の凍結乾燥製剤。
- FSH対LHの比率が約6:1〜約1:6の範囲内にある、請求項1〜11のいずれか1項に記載の凍結乾燥製剤。
- FSH対LHの比率が約4:1〜約1:2の範囲内にある、請求項12に記載の凍結乾燥製剤。
- FSH対LHの比率が約3:1〜約1:1の範囲内にある、請求項13に記載の凍結乾燥製剤。
- FSH対LHの比率が約2:1〜約1:1の範囲内にある、請求項14に記載の凍結乾燥製剤。
- 更にスクロースを含んで成る、請求項1〜15のいずれか1項に記載の凍結乾燥製剤。
- 更にメチオニンを含んで成る、請求項1〜16のいずれか1項に記載の凍結乾燥製剤。
- 更にリン酸緩衝液を含んで成る、請求項1〜17のいずれか1項に記載の凍結乾燥製剤。
- 以下の成分:rFSH、rLH、Tween 20、スクロース、メチオニン、リン酸緩衝液を含んで成る、請求項1〜18のいずれか1項に記載の凍結乾燥製剤。
- 12.0μgの組換えFSH、3.7μgの組換えLH、30.0mgのスクロース、0.45mgのNaH2PO4 H20、1.11mgのNa2HPO4 2H20、0.05mgのTween 20及び0.1mgのL−メチオニンを含んで成る、請求項1〜19のいずれか1項に記載の凍結乾燥製剤。
- 請求項1〜20のいずれか1項に記載の凍結乾燥製剤を充填した第一容器及び再構成用の溶媒を含んで成る第二容器を含んで成る製品。
- 第二容器が再構成用の水を含む、請求項21に記載の製品。
- 請求項1〜20のいずれか1項に記載の凍結乾燥製剤の製造方法であって、FSHとLT、そしてTween 20との混合物を形成する工程、及び当該混合物を凍結乾燥にかける工程を含んで成る方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP03101830 | 2003-06-20 | ||
EP03101830.2 | 2003-06-20 | ||
PCT/EP2004/051138 WO2004112826A1 (en) | 2003-06-20 | 2004-06-16 | Freeze-dried fsh / lh formulations |
Publications (2)
Publication Number | Publication Date |
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JP2009514777A true JP2009514777A (ja) | 2009-04-09 |
JP4871124B2 JP4871124B2 (ja) | 2012-02-08 |
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JP2006516157A Active JP4871124B2 (ja) | 2003-06-20 | 2004-06-16 | 凍結乾燥fsh/lh製剤 |
Country Status (15)
Country | Link |
---|---|
US (1) | US7740884B2 (ja) |
EP (1) | EP1638595B1 (ja) |
JP (1) | JP4871124B2 (ja) |
AU (1) | AU2004248931B2 (ja) |
CA (1) | CA2526099C (ja) |
CY (1) | CY1114121T1 (ja) |
DK (1) | DK1638595T3 (ja) |
ES (1) | ES2414705T3 (ja) |
HR (1) | HRP20130242T1 (ja) |
IL (1) | IL172353A (ja) |
NO (1) | NO330210B1 (ja) |
PL (1) | PL1638595T3 (ja) |
PT (1) | PT1638595E (ja) |
SI (1) | SI1638595T1 (ja) |
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JP2021525083A (ja) * | 2018-05-25 | 2021-09-24 | ジェンザイム・コーポレーション | 酸性スフィンゴミエリナーゼ欠損症を治療するための医薬組成物 |
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TWI369401B (en) * | 2005-07-05 | 2012-08-01 | Ares Trading Sa | Serum-free culture medium for the production of recombinant gonadotropins |
CN101347613B (zh) * | 2008-09-17 | 2011-10-26 | 上海天伟生物制药有限公司 | 几乎不含亚基的糖蛋白的组合物及其制备方法 |
KR101483165B1 (ko) * | 2009-12-22 | 2015-01-15 | 샹하이 테크웰 바이오파마슈티컬 컴퍼니, 리미티드 | 인간폐경성선자극호르몬의 조성물 |
WO2014159813A1 (en) | 2013-03-13 | 2014-10-02 | Moderna Therapeutics, Inc. | Long-lived polynucleotide molecules |
FI126979B (en) * | 2016-02-29 | 2017-09-15 | Faron Pharmaceuticals Oy | Lyophilized pharmaceutical formulation and use thereof |
US11376220B2 (en) | 2017-06-30 | 2022-07-05 | Therio, LLC | Single-injection methods and formulations to induce and control multiple ovarian follicles in bovine, caprine, ovine, camelid and other female animals |
CN108096199B (zh) * | 2018-01-15 | 2020-08-25 | 常州市第四制药厂有限公司 | 一种注射用奥美拉唑钠及制备方法 |
AR117743A1 (es) | 2019-12-30 | 2021-08-25 | Univ Nacional Del Litoral Unl | MÉTODO DE OBTENCIÓN DE UNA LÍNEA CELULAR DE MAMÍFERO QUE EXPRESA UNA HORMONA GONADOTROFINA CORIÓNICA EQUINA RECOMBINANTE (reCG), LÍNEA CELULAR QUE EXPRESA reCG, MÉTODO DE PRODUCCIÓN A ESCALA DE reCG, reCG, FORMULACIONES QUE LA CONTIENEN, ÁCIDOS NUCLEICOS QUE CODIFICAN PARA reCG Y USOS |
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- 2004-06-16 AU AU2004248931A patent/AU2004248931B2/en active Active
- 2004-06-16 EP EP04766052A patent/EP1638595B1/en not_active Revoked
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- 2004-06-16 DK DK04766052.7T patent/DK1638595T3/da active
- 2004-06-16 WO PCT/EP2004/051138 patent/WO2004112826A1/en active Application Filing
- 2004-06-16 JP JP2006516157A patent/JP4871124B2/ja active Active
- 2004-06-16 ES ES04766052T patent/ES2414705T3/es active Active
- 2004-06-16 US US10/561,529 patent/US7740884B2/en active Active
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Cited By (1)
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JP2021525083A (ja) * | 2018-05-25 | 2021-09-24 | ジェンザイム・コーポレーション | 酸性スフィンゴミエリナーゼ欠損症を治療するための医薬組成物 |
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Publication number | Publication date |
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NO330210B1 (no) | 2011-03-07 |
AU2004248931B2 (en) | 2009-07-16 |
SI1638595T1 (sl) | 2013-04-30 |
PL1638595T3 (pl) | 2013-06-28 |
IL172353A (en) | 2013-04-30 |
WO2004112826A1 (en) | 2004-12-29 |
DK1638595T3 (da) | 2013-04-08 |
CA2526099A1 (en) | 2004-12-29 |
PT1638595E (pt) | 2013-04-26 |
JP4871124B2 (ja) | 2012-02-08 |
NO20060241L (no) | 2006-01-17 |
HRP20130242T1 (hr) | 2013-04-30 |
CA2526099C (en) | 2013-02-05 |
CY1114121T1 (el) | 2016-07-27 |
AU2004248931A1 (en) | 2004-12-29 |
US20070059252A1 (en) | 2007-03-15 |
ES2414705T3 (es) | 2013-07-22 |
EP1638595B1 (en) | 2013-03-20 |
EP1638595A1 (en) | 2006-03-29 |
US7740884B2 (en) | 2010-06-22 |
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