JP2018538290A5 - - Google Patents
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- JP2018538290A5 JP2018538290A5 JP2018529574A JP2018529574A JP2018538290A5 JP 2018538290 A5 JP2018538290 A5 JP 2018538290A5 JP 2018529574 A JP2018529574 A JP 2018529574A JP 2018529574 A JP2018529574 A JP 2018529574A JP 2018538290 A5 JP2018538290 A5 JP 2018538290A5
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- estradiol
- vaginal
- vaginal suppository
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- 239000006216 vaginal suppository Substances 0.000 claims 73
- 229940120293 Vaginal Suppository Drugs 0.000 claims 59
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 claims 56
- 229960005309 Estradiol Drugs 0.000 claims 56
- 210000002381 Plasma Anatomy 0.000 claims 20
- 230000036470 plasma concentration Effects 0.000 claims 17
- 239000007788 liquid Substances 0.000 claims 9
- 239000000203 mixture Substances 0.000 claims 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 7
- 230000035839 C max Effects 0.000 claims 6
- 208000004483 Dyspareunia Diseases 0.000 claims 4
- 229940088597 Hormone Drugs 0.000 claims 4
- 206010047791 Vulvovaginal dryness Diseases 0.000 claims 4
- 239000000227 bioadhesive Substances 0.000 claims 4
- 230000002354 daily Effects 0.000 claims 4
- 238000011156 evaluation Methods 0.000 claims 4
- 239000005556 hormone Substances 0.000 claims 4
- 238000011179 visual inspection Methods 0.000 claims 4
- 239000007903 gelatin capsule Substances 0.000 claims 3
- IIRDTKBZINWQAW-UHFFFAOYSA-N hexaethylene glycol Chemical compound OCCOCCOCCOCCOCCOCCO IIRDTKBZINWQAW-UHFFFAOYSA-N 0.000 claims 3
- 239000002736 nonionic surfactant Substances 0.000 claims 3
- 239000002904 solvent Substances 0.000 claims 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-M stearate Chemical compound CCCCCCCCCCCCCCCCCC([O-])=O QIQXTHQIDYTFRH-UHFFFAOYSA-M 0.000 claims 3
- VLPFTAMPNXLGLX-UHFFFAOYSA-N Axona Chemical compound CCCCCCCC(=O)OCC(OC(=O)CCCCCCC)COC(=O)CCCCCCC VLPFTAMPNXLGLX-UHFFFAOYSA-N 0.000 claims 2
- 206010057671 Female sexual dysfunction Diseases 0.000 claims 2
- 210000003905 Vulva Anatomy 0.000 claims 2
- 230000001568 sexual Effects 0.000 claims 2
- LADGBHLMCUINGV-UHFFFAOYSA-N tricaprin Chemical compound CCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC LADGBHLMCUINGV-UHFFFAOYSA-N 0.000 claims 2
- -1 triglycerides ester Chemical class 0.000 claims 2
- 206010003694 Atrophy Diseases 0.000 claims 1
- 210000003756 Cervix Mucus Anatomy 0.000 claims 1
- 206010013990 Dysuria Diseases 0.000 claims 1
- 206010018987 Haemorrhage Diseases 0.000 claims 1
- 206010019233 Headache Diseases 0.000 claims 1
- 241001313288 Labia Species 0.000 claims 1
- 208000003251 Pruritus Diseases 0.000 claims 1
- 230000037098 T max Effects 0.000 claims 1
- 210000001215 Vagina Anatomy 0.000 claims 1
- 206010046910 Vaginal haemorrhage Diseases 0.000 claims 1
- 206010056530 Vulvovaginal pruritus Diseases 0.000 claims 1
- 230000037007 arousal Effects 0.000 claims 1
- 230000000740 bleeding Effects 0.000 claims 1
- 231100000319 bleeding Toxicity 0.000 claims 1
- 235000014113 dietary fatty acids Nutrition 0.000 claims 1
- 239000000262 estrogen Substances 0.000 claims 1
- 230000003203 everyday Effects 0.000 claims 1
- 239000000194 fatty acid Substances 0.000 claims 1
- 150000004665 fatty acids Chemical class 0.000 claims 1
- 231100000869 headache Toxicity 0.000 claims 1
- 238000005461 lubrication Methods 0.000 claims 1
- 210000004877 mucosa Anatomy 0.000 claims 1
- 229940068196 placebo Drugs 0.000 claims 1
- 239000000902 placebo Substances 0.000 claims 1
- 230000036299 sexual function Effects 0.000 claims 1
- 230000037303 wrinkles Effects 0.000 claims 1
Claims (27)
4μg〜25μgのエストラジオールを含み、
VVAを患う被験体に対して投与されるものであり、
前記投与は、毎日２週間、その後は週２回にわたり実施されるものであり、
前記治療が、最初の膣坐剤を投与した際、又は、最初の膣坐剤を投与してから2週間以内に効果がある、膣坐剤。 A vaginal suppository for treating symptoms of vulva vaginal atrophy (VVA), wherein the vaginal suppository comprises:
4 μg~25μg estradiol only free,
Administered to a subject suffering from VVA ,
The administration is performed for two weeks every day and thereafter twice a week,
A vaginal suppository , wherein the treatment is effective when the first vaginal suppository is administered or within 2 weeks after administering the first vaginal suppository .
（i）前記被験体の膣分泌のレベルの増加が、目視検査によって評価されること；
（ii）前記被験体の膣粘膜皺数の増加が、目視検査によって評価されること；
（iii）前記被験体の膣出血または点状出血の減少が、目視検査によって評価される；
（iv）前記被験体の膣粘膜の色の、透明からピンクへの、または淡いピンクからピンクへの変化が、目視検査によって評価されること；
（v）膣乾燥の重症度を、最初の膣坐剤を投与した際、又は、最初の膣坐剤を投与してから2週間以内に低下させること；
（vi）外陰部または膣のかゆみの重症度を、最初の膣坐剤を投与した際、又は、最初の膣坐剤を投与してから2週間以内に低下させること；
（vii）性交疼痛の重症度を、最初の膣坐剤を投与した際、又は、最初の膣坐剤を投与してから2週間以内に低下させること。 The vaginal suppository of claim 1, wherein the treatment comprises one or more of the following (i) to (vii) .
(I) increasing the level of vaginal secretion in the subject is assessed by visual inspection ;
(Ii) an increase in the number of vaginal mucosal wrinkles in the subject is assessed by visual inspection ;
(Iii) the reduction of vaginal or petechial bleeding in the subject is assessed by visual inspection ;
(Iv) the change in color of the subject's vaginal mucosa from transparent to pink or pale pink to pink is assessed by visual inspection ;
(V) reducing the severity of vaginal dryness when the first vaginal suppository is administered or within two weeks after the administration of the first vaginal suppository ;
(Vi) reducing the severity of vulvar or vaginal itching upon administration of the first vaginal suppository or within two weeks of administering the first vaginal suppository ;
(Vii) To reduce the severity of dyspareunia upon administration of the first vaginal suppository or within two weeks of administering the first vaginal suppository .
1）1日目の評価で約73.3pg*時間/mL〜約114.7pg*時間/mLに及ぶエストラジオールの未調整算術平均曲線下面積（AUC）0-24；
2）1日目の評価で約3.1pg/mL〜約4.8pg/mLに及ぶエストラジオールの補正算術平均ピーク血漿濃度（Cavg[0-24]）；
3）14日目の評価で約69.7pg*時間/mL〜約108.9pg*時間/mLに及ぶエストラジオールの未調整算術平均曲線下面積（AUC）0-24；および
4）14日目の評価で約2.8pg/mL〜約4.6pg/mLに及ぶエストラジオールの補正算術平均ピーク血漿濃度（Cavg [0-24]）；または、
（b）前記膣坐剤の投与が、該患者からの血漿試料において、1日目の評価で約2.0pg/mL〜約3.3pg/mLに及ぶエストラジオールの補正幾何平均ピーク血漿濃度（Cmax）を与えるか；
（c）前記膣坐剤の投与が、該患者からの血漿試料において、14日目の評価で約1.0pg/mL〜約1.7pg/mLに及ぶエストラジオールの補正幾何平均ピーク血漿濃度（Cmax）を与えるか；
（d）前記膣坐剤の投与が、該患者からの血漿試料において、1日目の評価で約9.5pg*時間/mL〜15.1pg*時間/mLに及ぶエストラジオールの補正幾何平均曲線下面積（AUC）0-24を与えるか;または、
（e）前記膣坐剤の投与が、該患者からの血漿試料において、14日目の評価で約5.7pg*時間/mL〜約9.1pg*時間/mLに及ぶエストラジオールの補正幾何平均曲線下面積（AUC）0-24を与える、
請求項６に記載の膣坐剤。 (A) administration of the vaginal suppositories in plasma samples from the patient, or provide one or more parameters selected from:
1) about 73.3Pg * time rating of 1 day / mL to about 114.7Pg * unadjusted arithmetic mean area under the curve of estradiol ranging time / mL (AUC) 0-24;
2) Estradiol corrected arithmetic mean peak plasma concentration (C avg [0-24] ) ranging from about 3.1 pg / mL to about 4.8 pg / mL on day 1 evaluation;
3) the area under the unadjusted arithmetic mean curve (AUC) of estradiol ranging from about 69.7 pg * h / mL to about 108.9 pg * h / mL on day 14, 0-24 ;
4) a corrected arithmetic mean peak plasma concentration of estradiol ranging from about 2.8 pg / mL to about 4.6 pg / mL on day 14 (C avg [0-24] ) ; or
(B) Corrected geometric mean peak plasma concentration (C max ) of estradiol ranging from about 2.0 pg / mL to about 3.3 pg / mL as assessed on day 1 in administration of the vaginal suppository in a plasma sample from the patient. Or give ;
Administration of (c) the vaginal suppositories in plasma samples from the patient, corrected geometric mean peak plasma concentration of estradiol up to about 1.0p g / mL to about 1.7p g / mL in the evaluation of day 14 (C max ) ;
(D) the area under the corrected geometric mean curve of estradiol, wherein administration of the vaginal suppository ranges from about 9.5 pg * h / mL to 15.1 pg * h / mL in a plasma sample from the patient, as assessed on day 1 ( AUC) gives 0-24 ; or
(E) the area under the corrected geometric mean curve of estradiol, wherein administration of the vaginal suppository ranges from about 5.7 pg * h / mL to about 9.1 pg * h / mL, as assessed on day 14, in a plasma sample from the patient. (AUC) gives 0-24 ,
A vaginal suppository according to claim 6 .
1）1日目の評価で約110.3pg*時間/mL〜約172.6pg*時間/mLに及ぶエストラジオールの未調整算術平均曲線下面積（AUC）0-24；
2）1日目の評価で約4.6pg/mL〜約7.8pg/mLに及ぶエストラジオールの補正算術平均ピーク血漿濃度（Cavg [0-24]）；
3）14日目の評価で約87.9pg*時間/mL〜約137.4pg*時間/mLに及ぶエストラジオールの未調整算術平均曲線下面積（AUC）0-24；および
4）14日目の評価で約3.6pg/mL〜約5.8pg/mLに及ぶエストラジオールの補正算術平均ピーク血漿濃度（Cavg [0-24]）;
（b）前記膣坐剤の投与が、該患者からの血漿試料において、1日目の評価で約4.7pg/mL〜約7.6pg/mLに及ぶエストラジオールの補正幾何平均ピーク血漿濃度（Cmax）を与えるか;
（c）前記膣坐剤の投与が、該患者からの血漿試料において、14日目の評価で約2.3pg/mL〜約3.8pg/mLに及ぶエストラジオールの補正幾何平均ピーク血漿濃度（Cmax）を与える；
（d）前記膣坐剤の投与が、該患者からの血漿試料において、1日目の評価で約17.5pg*時間/mL〜約27.4pg*時間/mLに及ぶエストラジオールの補正幾何平均曲線下面積（AUC）0-24を与えるか；
（e）前記膣坐剤の投与が、該患者からの血漿試料において、14日目の評価で約10.9pg*時間/mL〜約17.2pg*時間/mLに及ぶエストラジオールの補正幾何平均曲線下面積（AUC）0-24を与えるか；
（f）前記膣坐剤の投与が、該患者からの血漿試料において、1日目の評価で約0.6pg/mL〜約1.1pg/mLに及ぶエストラジオールの補正幾何平均ピーク血漿濃度（Cavg）を与えるか；または、
（g）前記膣坐剤の投与が、該患者からの血漿試料において、14日目の評価で約0.1pg/mL〜約0.3pg/mLに及ぶエストラジオールの補正幾何平均ピーク血漿濃度（Cavg）を与える、請求項８に記載の膣坐剤。 (A) whether the administration of the vaginal suppository provides one or more parameters selected from the following in a plasma sample from the patient ;
1) The area under the unadjusted arithmetic mean curve (AUC) of estradiol ranging from about 110.3 pg * hr / mL to about 172.6 pg * hr / mL on the first day, 0-24 ;
2) Estradiol corrected arithmetic mean peak plasma concentration (C avg [0-24] ) ranging from about 4.6 pg / mL to about 7.8 pg / mL on day 1 evaluation;
3) the area under the unadjusted arithmetic mean curve (AUC) of estradiol ranging from about 87.9 pg * hr / mL to about 137.4 pg * hr / mL on day 14, 0-24 ;
4) Estradiol corrected arithmetic mean peak plasma concentration (C avg [0-24] ) ranging from about 3.6 pg / mL to about 5.8 pg / mL on day 14 ;
(B) Corrected geometric mean peak plasma concentration (C max ) of estradiol ranging from about 4.7 pg / mL to about 7.6 pg / mL as assessed on day 1 in a plasma sample from the patient wherein administration of the vaginal suppository. Or give ;
(C) the administration of the vaginal suppository results in a corrected geometric mean peak plasma concentration (C max ) of estradiol ranging from about 2.3 pg / mL to about 3.8 pg / mL as assessed on day 14 in a plasma sample from the patient. Give ;
(D) the area under the corrected geometric mean curve of estradiol, wherein administration of the vaginal suppository ranges from about 17.5 pg * hr / mL to about 27.4 pg * hr / mL in a plasma sample from the patient as assessed on day 1 (AUC) Give 0-24 ;
(E) the area under the corrected geometric mean curve of estradiol, wherein administration of the vaginal suppository ranges from about 10.9 pg * hr / mL to about 17.2 pg * hr / mL in a plasma sample from the patient as assessed on day 14; (AUC) Give 0-24 ;
(F) Corrected geometric mean peak plasma concentration of estradiol (C avg ) ranging from about 0.6 pg / mL to about 1.1 pg / mL as assessed on day 1 in the plasma sample from said patient, wherein administration of said vaginal suppository. Or; or
(G) Corrected geometric mean peak plasma concentration (C avg ) of estradiol, wherein administration of the vaginal suppository ranges from about 0.1 pg / mL to about 0.3 pg / mL in a plasma sample from the patient, as assessed on day 14 The vaginal suppository of claim 8 , which provides
1）1日目の評価で約173.5pg*時間/mL〜約271.3pg*時間/mLに及ぶエストラジオールの未調整算術平均曲線下面積（AUC）0-24；
2）1日目の評価で約7.2pg/mL〜約11.4pg/mLに及ぶエストラジオールの補正算術平均ピーク血漿濃度（Cavg [0-24]）；
3）14日目の評価で約137.5pg*時間/mL〜約215.1pg*時間/mLに及ぶエストラジオールの未調整算術平均曲線下面積（AUC）0-24；および
4）14日目の評価で約5.7pg/mL〜約9.0pg/mLに及ぶエストラジオールの補正算術平均ピーク血漿濃度（Cavg [0-24]）；または、
（b）前記膣坐剤の投与が、該患者からの血漿試料において、1日目の評価で約20.9pg/mL〜約32.8pg/mLに及ぶエストラジオールの補正幾何平均ピーク血漿濃度（Cmax）を与えるか；
（c）前記膣坐剤の投与が、該患者からの血漿試料において、14日目の評価で約9.5pg/mL〜約15.1pg/mLに及ぶエストラジオールの補正幾何平均ピーク血漿濃度（Cmax）を与えるか；
（d）前記膣坐剤の投与が、該患者からの血漿試料において、1日目の評価で約104.3pg*時間/mL〜約163.1pg*時間/mLに及ぶエストラジオールの補正幾何平均曲線下面積（AUC）0-24を与えるか；
（e）前記膣坐剤の投与が、該患者からの血漿試料において、14日目の評価で約67.6pg*時間/mL〜約105.8pg*時間/mLに及ぶエストラジオールの補正幾何平均曲線下面積（AUC）0-24を与えるか；
（f）前記膣坐剤の投与が、該患者からの血漿試料において、1日目の評価で約4.3pg/mL〜約6.8pg/mLに及ぶエストラジオールの補正幾何平均ピーク血漿濃度（Cavg）を与えるか；
（g）前記膣坐剤の投与が、該患者からの血漿試料において、14日目の評価で約2.7pg/mL〜約4.4pg/mLに及ぶエストラジオールの補正幾何平均ピーク血漿濃度（Cavg）を与えるか；または、
（h）前記膣坐剤の投与が、該患者からの血漿試料において、約0.25時間〜約2時間のエストラジオールのピーク血漿濃度到達補正幾何平均時間（Tmax）を与える；
請求項１０に記載の膣坐剤。 (A) administration of the vaginal suppositories in plasma samples from the patient, or provide one or more parameters selected from the following;
1) The area under the unadjusted arithmetic mean curve (AUC) of estradiol ranging from about 173.5 pg * h / mL to about 271.3 pg * h / mL on day 1; 0-24 ;
2) Estradiol corrected arithmetic mean peak plasma concentration (C avg [0-24] ) ranging from about 7.2 pg / mL to about 11.4 pg / mL on day 1 evaluation;
3) Unadjusted arithmetic mean area under estradiol curve (AUC) 0-24 ranging from about 137.5 pg * hr / mL to about 215.1 pg * hr / mL on day 14;
4) a corrected arithmetic mean peak plasma concentration of estradiol ranging from about 5.7 pg / mL to about 9.0 pg / mL on the 14th day (C avg [0-24] ) ; or
(B) Corrected geometric mean peak plasma concentration (C max ) of estradiol, wherein administration of the vaginal suppository ranges from about 20.9 pg / mL to about 32.8 pg / mL in a plasma sample from the patient as assessed on day 1 Or give ;
(C) the administration of the vaginal suppository results in a corrected geometric mean peak plasma concentration (C max ) of estradiol ranging from about 9.5 pg / mL to about 15.1 pg / mL as assessed on day 14 in a plasma sample from the patient. Or give ;
(D) the area under the corrected geometric mean curve of estradiol, wherein administration of the vaginal suppository ranges from about 104.3 pg * h / mL to about 163.1 pg * h / mL in a plasma sample from the patient, as assessed on day 1; (AUC) Give 0-24 ;
(E) the area under the corrected geometric mean curve of estradiol, wherein administration of the vaginal suppository ranges from about 67.6 pg * h / mL to about 105.8 pg * h / mL in a plasma sample from the patient, as assessed on day 14; (AUC) Give 0-24 ;
(F) Corrected geometric mean peak plasma concentrations of estradiol (C avg ) ranging from about 4.3 pg / mL to about 6.8 pg / mL on day 1 in plasma samples from the patient after administration of the vaginal suppository. Or give ;
(G) Corrected geometric mean peak plasma concentration of estradiol (C avg ) ranging from about 2.7 pg / mL to about 4.4 pg / mL as assessed on day 14 in administration of the vaginal suppository in a plasma sample from the patient. Or; or
(H) administration of the vaginal suppository gives a corrected geometric mean time to peak plasma concentration of estradiol (T max ) of about 0.25 hours to about 2 hours in a plasma sample from the patient ;
A vaginal suppository according to claim 10.
（ii）前記膣坐剤においてエストラジオールが唯一の活性ホルモンであるか；または、
（iii）前記被験体が、前記膣坐剤の投与の約5分後に開始し、該膣坐剤の投与の約4時間後に終了する期間にわたって歩行可能な状態を維持する、
請求項１に記載の膣坐剤。 (I) whether or not the solubilizing agent contains a hydrophilic gel-forming bioadhesive ;
(Ii) estradiol is the only active hormone in the vaginal suppository ; or
(Iii) the subject is started after about 5 minutes of administration of the vaginal suppositories, maintaining a walkable state for a period ending about 4 hours after the administration of the vaginal suppositories,
A vaginal suppository according to claim 1 .
前記膣坐剤は、（a）治療有効量のエストラジオール；カプリル酸／カプリン酸トリグリセリド；ステアリン酸PEG-6およびパルミトステアリン酸エチレングリコールを含む非イオン性界面活性剤を含む液体組成物であり、前記治療有効量のエストラジオールとして約1マイクログラム〜約25マイクログラムのエストラジオールを含み、且つ、該膣坐剤においてエストラジオールが唯一の活性ホルモンである、液体組成物；ならびに（b）軟質ゼラチンカプセルを含む、
膣坐剤。 There vaginal suppositories to treat female sexual dysfunction, the vaginal suppository is to be administered it against the female subject in need,
The vaginal suppositories are, (a) a therapeutically effective amount of estradiol; a liquid composition comprising a nonionic surfactant comprising stearate PEG-6 and palmitostearate ethylene glycol; caprylic / capric triglyceride A liquid composition comprising from about 1 microgram to about 25 micrograms of estradiol as the therapeutically effective amount of estradiol, and wherein estradiol is the only active hormone in the vaginal suppository ; and (b) a soft gelatin capsule. Including ,
Vaginal suppositories .
約10μgのエストラジオールを含むか、または、
約25μgのエストラジオールを含む、
請求項１３に記載の膣坐剤。 Contains about 4 μg of estradiol,
Contains about 10 μg estradiol, or
Containing about 25 μg estradiol,
A vaginal suppository according to claim 13 .
前記膣坐剤は、（a）治療有効量のエストラジオール；カプリル酸／カプリン酸トリグリセリド；ステアリン酸PEG-6およびパルミトステアリン酸エチレングリコールを含む非イオン性界面活性剤を含む液体組成物であり、前記治療有効量のエストラジオールとして約1マイクログラム〜約25マイクログラムのエストラジオールを含み、且つ、該膣坐剤においてエストラジオールが唯一の活性ホルモンである、液体組成物；ならびに（b）軟質ゼラチンカプセルを含む、膣坐剤。 A vaginal suppository for treating vaginal dryness or dyspareunia , wherein the vaginal suppository is to be administered to a female subject in need thereof .
The vaginal suppositories are, (a) a therapeutically effective amount of estradiol; a liquid composition comprising a nonionic surfactant comprising stearate PEG-6 and palmitostearate ethylene glycol; caprylic / capric triglyceride A liquid composition comprising from about 1 microgram to about 25 micrograms of estradiol as the therapeutically effective amount of estradiol, and wherein estradiol is the only active hormone in the vaginal suppository ; and (b) a soft gelatin capsule. Including , vaginal suppositories .
約10μgのエストラジオールを含むか、または、
約25μgのエストラジオールを含む、
請求項１９に記載の膣坐剤。 Contains about 4 μg of estradiol ,
Contains about 10 μg estradiol, or
Containing about 25 μg estradiol,
A vaginal suppository according to claim 19 .
前記治療が、膣乾燥を2週間以内に緩和させる、
請求項１９に記載の膣坐剤。 The administration is performed daily for two weeks and thereafter twice a week,
Said treatment alleviates vaginal dryness within two weeks,
A vaginal suppository according to claim 19 .
前記治療が、最初の膣坐剤を投与した際、又は、最初の膣坐剤を投与してから2週間以内に、性交疼痛を緩和させる、請求項１９に記載の膣坐剤。 The administration is performed daily for two weeks and thereafter twice a week,
20. The vaginal suppository of claim 19, wherein the treatment alleviates dyspareunia upon administration of the first vaginal suppository or within two weeks of administering the first vaginal suppository .
約10μgのエストラジオールを含むか、または、
約25μgのエストラジオールを含む、
請求項２４に記載の膣坐剤。 It contains estradiol of about 4μg,
Contains about 10 μg estradiol, or
Containing about 25 μg estradiol,
A vaginal suppository according to claim 24 .
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| JP2021070619A JP2021119155A (en) | 2015-12-07 | 2021-04-19 | Vaginal Insertion Estradiol Pharmaceutical Compositions and Methods |
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| Application Number | Priority Date | Filing Date | Title |
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| US201562264309P | 2015-12-07 | 2015-12-07 | |
| US62/264,309 | 2015-12-07 | ||
| US201662296552P | 2016-02-17 | 2016-02-17 | |
| US62/296,552 | 2016-02-17 | ||
| US201662324838P | 2016-04-19 | 2016-04-19 | |
| US62/324,838 | 2016-04-19 | ||
| US201662329940P | 2016-04-29 | 2016-04-29 | |
| US62/329,940 | 2016-04-29 | ||
| US201662348820P | 2016-06-10 | 2016-06-10 | |
| US62/348,820 | 2016-06-10 | ||
| PCT/US2016/065466 WO2017100378A2 (en) | 2015-12-07 | 2016-12-07 | Vaginal inserted estradiol pharmaceutical compositions and methods |
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| Country | Link |
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| EP (1) | EP3386514A4 (en) |
| JP (2) | JP2018538290A (en) |
| KR (1) | KR20180100567A (en) |
| AU (1) | AU2016366200B2 (en) |
| BR (1) | BR112018011483A2 (en) |
| CA (1) | CA3007636A1 (en) |
| IL (1) | IL259884A (en) |
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| CA3159370A1 (en) * | 2019-10-31 | 2021-05-06 | R.P. Scherer Technologies, Llc | Suppository capsule |
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| FR2739558B1 (en) * | 1995-10-05 | 1997-11-28 | Innothera Lab Sa | UNITAL GALENIC FORM FOR LOCAL HORMONOTHERAPY OF VAGINAL DROUGHT |
| US6117446A (en) * | 1999-01-26 | 2000-09-12 | Place; Virgil A. | Drug dosage unit for buccal administration of steroidal active agents |
| BRPI0516243C1 (en) * | 2004-10-20 | 2021-05-25 | Endorecherche Inc | use of a sex steroid precursor selected from the group consisting of dehydroepiandrosterone, dehydroepiandrosterone sulfate, androst-5-ene-3b,17b-diol and 4-androsten-3,17-dione, use of said precursor in association with a selective estrogen receptor modulator for uterine and mammary gland protection against cancer, pharmaceutical composition and kit |
| BR112014031914B1 (en) * | 2012-06-18 | 2021-12-14 | Therapeuticsmd, Inc | ENCAPSULATED PHARMACEUTICAL FORMULATION FOR INTRAVAGINAL RELEASE INCLUDING ESTRADIOL AND USE THEREOF FOR THE TREATMENT OF VULVOVAGINAL ATROPHY AND AN ASSOCIATED SYSTEM, AS WELL AS AN ESTROGEN-DEFICIENT URINARY STATE |
| US10806697B2 (en) * | 2012-12-21 | 2020-10-20 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
| US9180091B2 (en) * | 2012-12-21 | 2015-11-10 | Therapeuticsmd, Inc. | Soluble estradiol capsule for vaginal insertion |
-
2016
- 2016-12-07 KR KR1020187019331A patent/KR20180100567A/en not_active Application Discontinuation
- 2016-12-07 WO PCT/US2016/065466 patent/WO2017100378A2/en active Application Filing
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