KR101722039B1 - 안구건조증 치료용 약학 조성물 - Google Patents

안구건조증 치료용 약학 조성물 Download PDF

Info

Publication number
KR101722039B1
KR101722039B1 KR1020167023214A KR20167023214A KR101722039B1 KR 101722039 B1 KR101722039 B1 KR 101722039B1 KR 1020167023214 A KR1020167023214 A KR 1020167023214A KR 20167023214 A KR20167023214 A KR 20167023214A KR 101722039 B1 KR101722039 B1 KR 101722039B1
Authority
KR
South Korea
Prior art keywords
pharmaceutical composition
eye
sfa
cyclosporin
composition
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
Application number
KR1020167023214A
Other languages
English (en)
Korean (ko)
Other versions
KR20160105533A (ko
Inventor
바스티안 테싱어
존야 테싱어
베른하르트 귄터
Original Assignee
노바리크 게엠베하
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=41731659&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=KR101722039(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by 노바리크 게엠베하 filed Critical 노바리크 게엠베하
Publication of KR20160105533A publication Critical patent/KR20160105533A/ko
Application granted granted Critical
Publication of KR101722039B1 publication Critical patent/KR101722039B1/ko
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • A61K38/13—Cyclosporins
    • 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
    • A61K47/08—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
    • 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
    • A61K9/0048—Eye, e.g. artificial tears
    • 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
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Ophthalmology & Optometry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Transplantation (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
KR1020167023214A 2009-12-14 2010-12-13 안구건조증 치료용 약학 조성물 Active KR101722039B1 (ko)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP09015423.8 2009-12-14
EP09015423A EP2335735A1 (en) 2009-12-14 2009-12-14 Pharmaceutical composition for treatment of dry eye syndrome
PCT/EP2010/069495 WO2011073134A1 (en) 2009-12-14 2010-12-13 Pharmaceutical composition for treatment of dry eye syndrome

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
KR1020127018066A Division KR101652714B1 (ko) 2009-12-14 2010-12-13 안구건조증 치료용 약학 조성물

Publications (2)

Publication Number Publication Date
KR20160105533A KR20160105533A (ko) 2016-09-06
KR101722039B1 true KR101722039B1 (ko) 2017-03-31

Family

ID=41731659

Family Applications (2)

Application Number Title Priority Date Filing Date
KR1020167023214A Active KR101722039B1 (ko) 2009-12-14 2010-12-13 안구건조증 치료용 약학 조성물
KR1020127018066A Active KR101652714B1 (ko) 2009-12-14 2010-12-13 안구건조증 치료용 약학 조성물

Family Applications After (1)

Application Number Title Priority Date Filing Date
KR1020127018066A Active KR101652714B1 (ko) 2009-12-14 2010-12-13 안구건조증 치료용 약학 조성물

Country Status (15)

Country Link
US (1) US8614178B2 (enExample)
EP (2) EP2335735A1 (enExample)
JP (5) JP5663595B2 (enExample)
KR (2) KR101722039B1 (enExample)
CN (1) CN102652022B (enExample)
AU (1) AU2010333039B2 (enExample)
BR (3) BR122020020872B1 (enExample)
CA (2) CA2776860C (enExample)
DK (1) DK2512515T3 (enExample)
ES (1) ES2449308T3 (enExample)
IN (1) IN2012DN03128A (enExample)
MX (1) MX2012006720A (enExample)
PL (1) PL2512515T3 (enExample)
PT (1) PT2512515E (enExample)
WO (1) WO2011073134A1 (enExample)

Families Citing this family (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2437684B1 (en) 2009-06-03 2022-06-15 ForSight Vision5, Inc. Anterior segment drug delivery
ES2564502T3 (es) 2010-03-17 2016-03-23 Novaliq Gmbh Composición farmacéutica para el tratamiento de la presión intraocular aumentada
EP2444063A1 (en) 2010-10-20 2012-04-25 Novaliq GmbH Liquid pharmaceutical compositions for the delivery of active ingredients
EP2462921A1 (en) 2010-11-11 2012-06-13 Novaliq GmbH Liquid pharmaceutical compositions for the treatment of a posterior eye disease
CN103561724B (zh) 2011-05-25 2016-06-29 诺瓦利克有限责任公司 给药给甲的药物组合物
JP6039145B2 (ja) 2011-05-25 2016-12-07 ノバリック ゲーエムベーハー 半フッ化アルカンを基礎にした局所薬学的組成物
PT2806886T (pt) 2012-01-23 2017-03-24 Novaliq Gmbh Composições de proteínas estabilizadas baseadas em alcanos semifluorados
MX363182B (es) * 2012-09-12 2019-03-13 Novaliq Gmbh Composiciones que comprenden mezclas de alcanos semifluorados.
EP2895144B1 (en) 2012-09-12 2017-01-11 Novaliq GmbH Semifluorinated alkane compositions
PL2708228T3 (pl) 2012-09-12 2018-11-30 Novaliq Gmbh Kompozycje do przemywania oczu
EP2730291A1 (en) * 2012-11-09 2014-05-14 Fluoron Gmbh Internal Tamponade Composition
US10172789B2 (en) 2013-01-24 2019-01-08 Palvella Therapeutics Llc Compositions for transdermal delivery of mTOR inhibitors
JP6304475B2 (ja) * 2013-01-31 2018-04-04 ロート製薬株式会社 点眼剤
TWI623313B (zh) * 2013-03-13 2018-05-11 Santen Pharmaceutical Co Ltd 瞼板腺功能障礙之治療劑
DK3024484T3 (en) 2013-07-23 2018-10-08 Novaliq Gmbh STABILIZED ANTIBODY COMPOSITIONS
US20160243291A1 (en) * 2013-10-15 2016-08-25 Forsight Vision5, Inc. Formulations and Methods for Increasing or Reducing Mucus
US20200237859A1 (en) 2019-01-25 2020-07-30 Newport Research, Inc. Aqueous suspensions of cyclosporin
US11324800B2 (en) 2015-01-15 2022-05-10 Wellspring Ophthalmics, Inc. Aqueous suspensions of cyclosporin
EP3283004A4 (en) 2015-04-13 2018-12-05 Forsight Vision5, Inc. Ocular insert composition of semi-crystalline or crystalline pharmaceutically active agent
US11013403B2 (en) * 2015-09-29 2021-05-25 The Regents Of The University Of California Methods of diagnosing diseases of mucosal surfaces
US20170087100A1 (en) 2015-09-30 2017-03-30 Novaliq Gmbh Semifluorinated compounds and their compositions
EP3722274B1 (en) * 2015-09-30 2023-06-07 Novaliq GmbH 2-perfluorobutyl pentane for ophthalmic administration
DK3442480T3 (da) 2016-06-23 2020-01-13 Novaliq Gmbh Fremgangsmåde til topisk indgivelse
KR102614858B1 (ko) 2016-09-22 2023-12-18 노바리크 게엠베하 안검염 치료에 사용되는 약제학적 조성물
AU2017329983B2 (en) * 2016-09-23 2022-05-05 Novaliq Gmbh Ophthalmic compositions comprising ciclosporin
CN109803650A (zh) * 2016-09-28 2019-05-24 诺瓦利克有限责任公司 包含大麻素受体结合配体的组合物
WO2018114557A1 (en) * 2016-12-22 2018-06-28 Novaliq Gmbh Compositions comprising tacrolimus for the treatment of intraocular inflammatory eye diseases
MX381639B (es) * 2016-12-23 2025-03-13 Novaliq Gmbh Composicion oftalmica para el tratamiento de la enfermedad del ojo seco.
WO2018129364A1 (en) 2017-01-06 2018-07-12 Palvella Therapeutics Llc Anhydrous compositions of mtor inhibitors and methods of use
PL3612228T3 (pl) 2017-04-21 2024-04-08 Dermaliq Therapeutics, Inc. Kompozycje jodu
US10717691B2 (en) 2017-05-05 2020-07-21 Novaliq Gmbh Process for the production of semifluorinated alkanes
US11278503B2 (en) 2017-05-12 2022-03-22 Novaliq Gmbh Pharmaceutical compositions comprising semifluorinated alkanes for the treatment of contact lense-related conditions
JP7814839B2 (ja) 2017-09-27 2026-02-17 ノバリック ゲーエムベーハー 眼疾患の治療に使用するためのラタノプロストを含む眼科用組成物
CN111182893A (zh) 2017-10-04 2020-05-19 诺瓦利克有限责任公司 包含f6h8的眼用组合物
US11576893B2 (en) 2018-03-02 2023-02-14 Novaliq Gmbh Pharmaceutical compositions comprising nebivolol
AU2019246035B2 (en) 2018-03-28 2024-07-18 Novaliq Gmbh Pharmaceutical composition comprising timolol
JP7855312B2 (ja) 2018-04-27 2026-05-08 ノバリック ゲーエムベーハー 緑内障の治療のためのタフルプロストを含む眼科用組成物
EP3817743A4 (en) 2018-07-02 2022-07-06 Palvella Therapeutics, Inc. ANHYDROUS COMPOSITIONS OF MTOR INHIBITORS AND METHODS OF USE
EP3852734A1 (en) 2018-09-22 2021-07-28 Novaliq GmbH Ophthalmic compositions for treatment of ocular surface damage and symptoms of dryness
WO2020064549A1 (en) 2018-09-27 2020-04-02 Novaliq Gmbh Lipid barrier repair
CA3112031A1 (en) 2018-10-12 2020-04-16 Novaliq Gmbh Ophthalmic composition for treatment of dry eye disease
CN113518619A (zh) * 2019-01-21 2021-10-19 诺瓦利克有限责任公司 用于治疗眼部新生血管形成的药物组合物
EP3923907B1 (en) 2019-02-13 2024-09-25 Novaliq GmbH Compositions and methods for the treatment of ocular neovascularization
WO2020239646A1 (en) 2019-05-24 2020-12-03 Novaliq Gmbh Ophthalmic composition for the treatment of ocular allergy
CN114449999A (zh) 2019-09-06 2022-05-06 诺瓦利克有限责任公司 用于治疗葡萄膜炎的眼用组合物
WO2021048803A1 (en) 2019-09-13 2021-03-18 Minas Coroneo Eye drop dispenser
EP3861857A1 (en) * 2020-02-07 2021-08-11 Novaliq GmbH Antiparasitic compositions
WO2021191273A1 (en) 2020-03-24 2021-09-30 Hovione Scientia Limited Compositions for use in treating meibomian gland dysfunction
US11191751B1 (en) * 2020-10-08 2021-12-07 Ads Therapeutics Llc Topical ophthalmological atropine free base compositions
EP4606396A4 (en) * 2022-11-11 2025-12-03 Cardio Navi Medtech Wuhan Co Ltd Coating solution for drug-coated balloons, coating material, drug-coated balloon, its preparation process and use
EP4665377A1 (en) * 2023-02-13 2025-12-24 Novaliq GmbH Ophthalmic composition for ocular surgery preparation in patients with ocular surface disease
AU2023270196B2 (en) * 2023-11-20 2025-06-26 Dyer, Gordon Wayne DR Method of Arthropod Egress
WO2026104414A1 (en) * 2024-11-12 2026-05-21 Dermaliq Therapeutics Gmbh Topical compositions for the treatment of alopecia areata

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996040052A1 (en) 1995-06-07 1996-12-19 Alliance Pharmaceutical Corp. Fluorochemical solutions for the delivery of lipophilic pharmaceutical agents
US6262126B1 (en) 1995-09-29 2001-07-17 Hasso Meinert Semi-fluorinated alkanes and their use
WO2005123035A1 (en) 2004-06-08 2005-12-29 Ocularis Pharma, Inc. Hydrophobic ophthalmic compositions and methods of use

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4839342A (en) 1987-09-03 1989-06-13 University Of Georgia Research Foundation, Inc. Method of increasing tear production by topical administration of cyclosporin
WO1989001772A1 (en) 1987-09-03 1989-03-09 University Of Georgia Research Foundation, Inc. Ocular cyclosporin composition
DE19861012A1 (de) * 1998-03-18 1999-09-30 Pharm Pur Gmbh Behandlungsmittel für die Ophthalmologie
CZ20013769A3 (cs) * 1999-04-30 2002-03-13 Sucampo Ag Činidlo pro léčbu suchého oka
DE19938668B4 (de) * 1999-08-14 2006-01-26 Bausch & Lomb Inc. Tränenersatzmittel
US20030018044A1 (en) * 2000-02-18 2003-01-23 Peyman Gholam A. Treatment of ocular disease
US20080019926A1 (en) * 2004-04-19 2008-01-24 Marie-Pierre Krafft Lung Surfactant Supplements
DE102007055046A1 (de) * 2007-11-19 2009-05-28 Fluoron Gmbh Infusionslösung
PL2110126T3 (pl) 2008-04-18 2012-04-30 Novaliq Gmbh Zastosowanie do inhalacji i zakraplania semifluorowanych alkanów jako nośników substancji aktywnych w strefie wewnątrzpłucnej

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996040052A1 (en) 1995-06-07 1996-12-19 Alliance Pharmaceutical Corp. Fluorochemical solutions for the delivery of lipophilic pharmaceutical agents
US6262126B1 (en) 1995-09-29 2001-07-17 Hasso Meinert Semi-fluorinated alkanes and their use
WO2005123035A1 (en) 2004-06-08 2005-12-29 Ocularis Pharma, Inc. Hydrophobic ophthalmic compositions and methods of use

Also Published As

Publication number Publication date
WO2011073134A1 (en) 2011-06-23
PT2512515E (pt) 2014-03-04
BR112012014190B8 (pt) 2021-05-25
JP6096731B2 (ja) 2017-03-15
AU2010333039B2 (en) 2014-08-28
JP6397472B2 (ja) 2018-09-26
BR112012014190B1 (pt) 2021-03-02
KR20120115977A (ko) 2012-10-19
CA2941956C (en) 2018-09-04
AU2010333039A1 (en) 2012-07-12
EP2512515B1 (en) 2013-12-25
JP2019070003A (ja) 2019-05-09
MX2012006720A (es) 2012-07-30
JP2019006803A (ja) 2019-01-17
JP6731039B2 (ja) 2020-07-29
US8614178B2 (en) 2013-12-24
BR122020020872B1 (pt) 2021-09-08
IN2012DN03128A (enExample) 2015-09-18
JP2013513586A (ja) 2013-04-22
BR122017018955B1 (pt) 2022-03-08
KR101652714B1 (ko) 2016-09-01
PL2512515T3 (pl) 2014-05-30
EP2335735A1 (en) 2011-06-22
BR112012014190A2 (pt) 2016-05-31
CA2776860A1 (en) 2011-06-23
CA2776860C (en) 2016-10-25
JP2015028064A (ja) 2015-02-12
CA2941956A1 (en) 2011-06-23
US20120244177A1 (en) 2012-09-27
JP2017078086A (ja) 2017-04-27
KR20160105533A (ko) 2016-09-06
HK1172269A1 (en) 2013-04-19
DK2512515T3 (en) 2014-03-10
ES2449308T3 (es) 2014-03-19
EP2512515A1 (en) 2012-10-24
JP5663595B2 (ja) 2015-02-04
CN102652022A (zh) 2012-08-29
CN102652022B (zh) 2014-12-17

Similar Documents

Publication Publication Date Title
KR101652714B1 (ko) 안구건조증 치료용 약학 조성물
KR101656121B1 (ko) 안압 증가를 치료하기 위한 약학 조성물
AU2017380769B2 (en) Compositions comprising tacrolimus for the treatment of intraocular inflammatory eye diseases
HK1172269B (en) Pharmaceutical composition for treatment of dry eye syndrome

Legal Events

Date Code Title Description
A107 Divisional application of patent
PA0104 Divisional application for international application

Comment text: Divisional Application for International Patent

Patent event code: PA01041R01D

Patent event date: 20160824

Application number text: 1020127018066

Filing date: 20120711

PG1501 Laying open of application
A201 Request for examination
PA0201 Request for examination

Patent event code: PA02012R01D

Patent event date: 20160923

Comment text: Request for Examination of Application

E701 Decision to grant or registration of patent right
PE0701 Decision of registration

Patent event code: PE07011S01D

Comment text: Decision to Grant Registration

Patent event date: 20170103

GRNT Written decision to grant
PR0701 Registration of establishment

Comment text: Registration of Establishment

Patent event date: 20170327

Patent event code: PR07011E01D

PR1002 Payment of registration fee

Payment date: 20170328

End annual number: 3

Start annual number: 1

PG1601 Publication of registration
J202 Request for trial for correction [limitation]
PJ0202 Trial for correction

Comment text: Request for Trial

Patent event date: 20180330

Patent event code: PJ02022R01D

Comment text: Registration of Establishment

Patent event date: 20170327

Patent event code: PJ02021E01I

Appeal kind category: Correction

Decision date: 20190625

Request date: 20180330

Appeal identifier: 2018105000040

J301 Trial decision

Free format text: TRIAL NUMBER: 2018105000040; TRIAL DECISION FOR CORRECTION REQUESTED 20180330

Effective date: 20190625

PJ1301 Trial decision

Patent event code: PJ13011S03D

Patent event date: 20190625

Comment text: Trial Decision on Correction (Patent, Utility Model)

Appeal kind category: Correction

Request date: 20180330

Decision date: 20190625

Appeal identifier: 2018105000040

G170 Re-publication after modification of scope of protection [patent]
PG1701 Publication of correction

Publication date: 20190704

FPAY Annual fee payment

Payment date: 20200320

Year of fee payment: 4

PR1001 Payment of annual fee

Payment date: 20200320

Start annual number: 4

End annual number: 4

FPAY Annual fee payment

Payment date: 20210319

Year of fee payment: 5

PR1001 Payment of annual fee

Payment date: 20210319

Start annual number: 5

End annual number: 5

FPAY Annual fee payment

Payment date: 20220318

Year of fee payment: 6

PR1001 Payment of annual fee

Payment date: 20220318

Start annual number: 6

End annual number: 6

PR1001 Payment of annual fee

Payment date: 20240314

Start annual number: 8

End annual number: 8