ES2597784T3 - Combinación de extracto de raíz de valeriana y aceite de lavanda para utilizar en el tratamiento de trastornos del sueño - Google Patents
Combinación de extracto de raíz de valeriana y aceite de lavanda para utilizar en el tratamiento de trastornos del sueño Download PDFInfo
- Publication number
- ES2597784T3 ES2597784T3 ES14176927.3T ES14176927T ES2597784T3 ES 2597784 T3 ES2597784 T3 ES 2597784T3 ES 14176927 T ES14176927 T ES 14176927T ES 2597784 T3 ES2597784 T3 ES 2597784T3
- Authority
- ES
- Spain
- Prior art keywords
- root extract
- lavender oil
- valerian root
- combination
- treatment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000000171 lavandula angustifolia l. flower oil Substances 0.000 title abstract description 11
- 229940038779 valerian root extract Drugs 0.000 title abstract description 5
- 239000001192 valeriana officinalis l. rhizome/root Substances 0.000 title abstract description 5
- 208000019116 sleep disease Diseases 0.000 title abstract 2
- 238000011282 treatment Methods 0.000 title abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 6
- 244000126014 Valeriana officinalis Species 0.000 abstract description 6
- 235000013832 Valeriana officinalis Nutrition 0.000 abstract description 6
- 235000016788 valerian Nutrition 0.000 abstract description 6
- 235000010701 Lavanda vera Nutrition 0.000 abstract description 2
- 244000178870 Lavandula angustifolia Species 0.000 abstract description 2
- 235000010663 Lavandula angustifolia Nutrition 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract 6
- 238000000605 extraction Methods 0.000 abstract 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract 2
- 239000003921 oil Substances 0.000 abstract 1
- 238000011321 prophylaxis Methods 0.000 abstract 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 6
- 235000012239 silicon dioxide Nutrition 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000007788 liquid Substances 0.000 description 3
- 229920002785 Croscarmellose sodium Polymers 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 229960001681 croscarmellose sodium Drugs 0.000 description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 239000004408 titanium dioxide Substances 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 239000012073 inactive phase Substances 0.000 description 1
- 239000004407 iron oxides and hydroxides Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000001238 valeriana officinalis l. root oil Substances 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/84—Valerianaceae (Valerian family), e.g. valerian
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Botany (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Anesthesiology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Psychology (AREA)
- Pulmonology (AREA)
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Combinación que comprende un contenido de extracto de raíz de valeriana (extracto de raíces secas de Valeriana officinalis) y aceite de lavanda (aceite de flores de Lavandula officinalis) para utilizar por vía oral en el tratamiento o la profilaxis de trastornos del sueño, en la que el extracto de raíz de valeriana se prepara por extracción con etanol acuoso o metanol acuoso, en donde se utilizan para la extracción etanol y agua en una proporción de volumen de 30/70 a 90/10, o metanol y agua en una proporción de volumen de 40/60 a 55/45.
Description
sobre todo en la corteza, pero principalmente también durante la tercera a quinta horas siguientes a la administración (véanse Figs. 1, 2, 3 y Fig. 7).
La administración por vía oral de la combinación de extracto de raíz de valeriana y aceite de lavanda como dosis individuales dio lugar a variaciones extremadamente evidentes y estadísticamente significativas de la actividad
5 eléctrica del cerebro en los animales de experimentación, que se correspondieron con las registradas durante el sueño. En particular, resulta sorprendente comprobar que los preparados se administraron por la mañana, es decir, después del descanso nocturno (fase inactiva).
Ejemplo 1: Preparación de un extracto de raíz de valeriana según la Ph. Eur.
Raíces desecadas de Valeriana officinalis se extrajeron dos veces con siete veces la cantidad en peso de etanol al
10 70% (en volumen) a 60ºC durante 1 h. La mezcla enfriada se filtró. El filtrado se concentró y, a continuación, se secó a 60ºC y 25 mbar durante 8 h; rendimiento de 24% de extracto seco.
Ejemplo 2: Preparación de un aceite de lavanda según la Ph. Eur.
Flores frescas de Lavandula officinalis se sometieron a una destilación en vapor de agua según la Ph. Eur. El aceite etérico obtenido de esta forma se siguió purificando por destilación a una temperatura máxima de 120ºC y 10 a 20
15 mbar.
Ejemplo 3: Preparado de combinación en forma de comprimido recubierto
Tabla 2: Composición del comprimido recubierto con 500 mg de extracto seco de raíz de valeriana y 80 mg de aceite de lavanda
- Posición
- Sustancia presente Cantidad por comprimido (mg) Cantidad por lote de fabricación para 30.000 comprimidos (kg)
- 1
- Extracto seco de raíz de valeriana 500,0 15,00
- 2
- Dióxido de silicio precipitado 100,0 3,00
- 3
- Aceite de lavanda 80,0 2,40
- 4
- Celulosa microcristalina 200,0 6,00
- 5
- Croscarmelosa sódica 40,0 1,20
- 6
- Dióxido de silicio precipitado 20,0 0,60
- 7
- Estearato de magnesio 5,0 0,15
- 8
- Hipromelosa 40,0 1,20
- 9
- Macrogol 1500 8,0 0,24
- 10
- Dióxido de titanio E171 6,0 0,18
- 11
- Óxido de hierro amarillo E172 3,0 0,09
- 12
- Talco 3,0 0,09
- 1005,0
- 30,15
20 Para la preparación de un comprimido con 500 mg de extracto seco de raíz de valeriana y 80 mg de aceite de lavanda líquido, se mezclan intensivamente 15 kg de extracto seco de raíz de valeriana (Posición 1) con 3 kg de dióxido de silicio precipitado (Posición 2). A continuación, a esta mezcla se agregan 2,4 kg de aceite de lavanda (Posición 3) y se mezcla nuevamente de forma intensiva. Se forma una mezcla pulverulenta sin partes líquidas. Si la mezcla de extracto seco de raíz de valeriana y aceite de lavanda se efectúa sin dióxido de silicio precipitado, el
25 aceite de lavanda se separa en forma líquida y la mezcla no es apropiada para el procesamiento posterior en comprimidos.
La mezcla de extracto seco de raíz de valeriana, dióxido de silicio y aceite de lavanda se combina y mezcla con celulosa microcristalina (carga y aglutinante; Posición 4), croscarmelosa sódica (acelerador de la disgregación; Posición 5), dióxido de silicio precipitado (agente regulador de fluidez; Posición 6). Seguidamente, se agregan
30 estearato de magnesio (lubricante; Posición 7) y se vuelve a mezclar brevemente durante 5 minutos.
7
Claims (1)
-
imagen1
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14176927.3A EP2974733B1 (de) | 2014-07-14 | 2014-07-14 | Kombination von Baldrianwurzelextrakt und Lavendelöl zur Verwendung zur Behandlung von Schlafstörungen |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2597784T3 true ES2597784T3 (es) | 2017-01-23 |
Family
ID=51167804
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES14176927.3T Active ES2597784T3 (es) | 2014-07-14 | 2014-07-14 | Combinación de extracto de raíz de valeriana y aceite de lavanda para utilizar en el tratamiento de trastornos del sueño |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US10357530B2 (es) |
| EP (1) | EP2974733B1 (es) |
| JP (1) | JP6474114B2 (es) |
| KR (1) | KR102231129B1 (es) |
| CN (1) | CN106573029B (es) |
| AU (1) | AU2015291363B2 (es) |
| CA (1) | CA2953190C (es) |
| ES (1) | ES2597784T3 (es) |
| HU (1) | HUE031669T2 (es) |
| MX (1) | MX2017000472A (es) |
| MY (1) | MY177827A (es) |
| PL (1) | PL2974733T3 (es) |
| PT (1) | PT2974733T (es) |
| RU (1) | RU2672876C2 (es) |
| TW (1) | TWI654987B (es) |
| WO (1) | WO2016008650A1 (es) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2017260019A1 (en) | 2016-05-06 | 2018-11-22 | Sociétés des Produits Nestlé S.A. | Valerian composition and related methods |
| CN108042658A (zh) * | 2017-11-17 | 2018-05-18 | 贵州苗药生物技术有限公司 | 一种缬草苗药睡眠精油组合物及其制备方法和应用 |
| JP6961481B2 (ja) * | 2017-12-26 | 2021-11-05 | 株式会社ファンケル | 脳血流改善用組成物 |
| CN111388572A (zh) * | 2020-04-13 | 2020-07-10 | 北京中医药大学 | 一种复方精油及其制备方法、制剂和应用 |
| KR20240134719A (ko) * | 2022-01-18 | 2024-09-10 | 옴니액티브 헬스 테크놀로지스 리미티드 | 수면 관리용 발레리안 조성물 |
| CN118600573B (zh) * | 2024-04-10 | 2025-02-07 | 和也健康科技有限公司 | 一种薰衣草、缬草改性植物基纤维及其制备方法 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2106873C1 (ru) * | 1994-03-16 | 1998-03-20 | Николай Николаевич Бобров-Егоров | Бальзамическое биологически активное средство - фитаон-4 и способ его получения |
| JPH1025246A (ja) | 1996-07-11 | 1998-01-27 | Kobayashi Pharmaceut Co Ltd | 催眠剤、催眠性飲食物及び催眠性餌料 |
| RU2215536C2 (ru) * | 1999-07-15 | 2003-11-10 | Сергей Иванович Гулый | Биологически активная пищевая добавка лечебно-профилактического действия, обладающая седативными свойствами, способ ее получения |
| US6869622B2 (en) | 1999-07-21 | 2005-03-22 | Ancile Pharmaceuticals, Inc. | Composition for improving sleep quality and efficiency, and methods of preparing and using the composition |
| DE102004048716A1 (de) * | 2004-10-06 | 2006-04-20 | Dr. Willmar Schwabe Gmbh & Co. Kg | Verwendung von Lavendelöl zur Prophylaxe und Behandlung von Neurasthenie, Somatisierungsstörungen und von anderen stress-assoziierten Erkrankungen |
| WO2007095716A1 (en) * | 2006-02-23 | 2007-08-30 | Iomedix Sleep International Srl | Compositions and methods for the induction and maintenance of quality sleep |
| US20090061029A1 (en) * | 2007-08-28 | 2009-03-05 | Kaira Rouda | Nighttime water |
| KR20110089169A (ko) * | 2008-12-03 | 2011-08-04 | 이엘씨 매니지먼트 엘엘씨 | 이완 상태를 촉진하는 조성물 및 방법 |
| EP2533790A2 (de) * | 2010-02-09 | 2012-12-19 | Reiner Rittinghausen | Zusammmensetzung zur behandlung und prophylaxe von nervösen störungen und schlafstörungen |
| KR20130102468A (ko) * | 2010-05-10 | 2013-09-17 | 세게티스, 인코포레이티드. | 방향 제형，이의 제조 방법 및 이를 포함하는 물품 |
| KR20120122109A (ko) * | 2011-04-28 | 2012-11-07 | 애경산업(주) | 허브 추출물을 함유하는 탈모 방지 및 양모 촉진용 모발 또는 두피 화장료 조성물 |
| US20130004599A1 (en) * | 2011-06-30 | 2013-01-03 | Masada Health & Beauty Corporation | Formulation for transdermal delivery to promote sleep |
| KR101296920B1 (ko) * | 2013-01-21 | 2013-08-14 | 강영숙 | 숙면을 위한 마사지 오일 |
| CN103142910B (zh) * | 2013-03-08 | 2014-07-09 | 张风华 | 安神脐贴 |
| US9375463B2 (en) * | 2013-09-10 | 2016-06-28 | Creative Medical Health, Inc. | Compositions and methods for improving sleep using a nutraceutical formulation |
| CN103750535B (zh) * | 2014-01-22 | 2015-12-02 | 红云红河烟草(集团)有限责任公司 | 一种加热非燃烧型卷烟烟块的制备方法 |
| WO2015142611A1 (en) * | 2014-03-20 | 2015-09-24 | Santé, Llc | Pre-operative beverages |
-
2014
- 2014-07-14 HU HUE14176927A patent/HUE031669T2/en unknown
- 2014-07-14 PL PL14176927T patent/PL2974733T3/pl unknown
- 2014-07-14 ES ES14176927.3T patent/ES2597784T3/es active Active
- 2014-07-14 EP EP14176927.3A patent/EP2974733B1/de active Active
- 2014-07-14 PT PT141769273T patent/PT2974733T/pt unknown
-
2015
- 2015-06-10 JP JP2017502250A patent/JP6474114B2/ja active Active
- 2015-06-10 MX MX2017000472A patent/MX2017000472A/es active IP Right Grant
- 2015-06-10 US US15/326,247 patent/US10357530B2/en active Active
- 2015-06-10 AU AU2015291363A patent/AU2015291363B2/en not_active Ceased
- 2015-06-10 CN CN201580038895.0A patent/CN106573029B/zh not_active Expired - Fee Related
- 2015-06-10 KR KR1020177003954A patent/KR102231129B1/ko active Active
- 2015-06-10 MY MYPI2016704711A patent/MY177827A/en unknown
- 2015-06-10 RU RU2017101445A patent/RU2672876C2/ru active
- 2015-06-10 CA CA2953190A patent/CA2953190C/en active Active
- 2015-06-10 WO PCT/EP2015/062891 patent/WO2016008650A1/de active Application Filing
- 2015-06-23 TW TW104120187A patent/TWI654987B/zh active
Also Published As
| Publication number | Publication date |
|---|---|
| PT2974733T (pt) | 2016-10-24 |
| WO2016008650A1 (de) | 2016-01-21 |
| HUE031669T2 (en) | 2017-07-28 |
| TW201613628A (en) | 2016-04-16 |
| CA2953190A1 (en) | 2016-01-21 |
| EP2974733B1 (de) | 2016-09-07 |
| CA2953190C (en) | 2022-05-24 |
| RU2672876C2 (ru) | 2018-11-20 |
| TWI654987B (zh) | 2019-04-01 |
| US10357530B2 (en) | 2019-07-23 |
| MY177827A (en) | 2020-09-23 |
| US20170296612A1 (en) | 2017-10-19 |
| KR102231129B1 (ko) | 2021-03-24 |
| AU2015291363B2 (en) | 2020-04-02 |
| AU2015291363A1 (en) | 2017-01-12 |
| PL2974733T3 (pl) | 2017-09-29 |
| CN106573029B (zh) | 2021-05-11 |
| KR20170029604A (ko) | 2017-03-15 |
| JP2017521446A (ja) | 2017-08-03 |
| EP2974733A1 (de) | 2016-01-20 |
| RU2017101445A3 (es) | 2018-08-14 |
| JP6474114B2 (ja) | 2019-02-27 |
| RU2017101445A (ru) | 2018-08-14 |
| CN106573029A (zh) | 2017-04-19 |
| MX2017000472A (es) | 2017-04-27 |
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