WO2012085185A1 - Aqueous solution of ambroxol - Google Patents

Aqueous solution of ambroxol Download PDF

Info

Publication number
WO2012085185A1
WO2012085185A1 PCT/EP2011/073754 EP2011073754W WO2012085185A1 WO 2012085185 A1 WO2012085185 A1 WO 2012085185A1 EP 2011073754 W EP2011073754 W EP 2011073754W WO 2012085185 A1 WO2012085185 A1 WO 2012085185A1
Authority
WO
WIPO (PCT)
Prior art keywords
aqueous solution
ambroxol
solution according
total content
glycol
Prior art date
Application number
PCT/EP2011/073754
Other languages
English (en)
French (fr)
Inventor
Gianluigi PASSETTI
Original Assignee
Advance Holdings Limited
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=45094329&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2012085185(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority to KR1020137013725A priority Critical patent/KR20130140042A/ko
Priority to MX2013005500A priority patent/MX2013005500A/es
Priority to CA2817453A priority patent/CA2817453A1/en
Priority to EA201300535A priority patent/EA201300535A1/ru
Priority to BR112013012815A priority patent/BR112013012815A2/pt
Application filed by Advance Holdings Limited filed Critical Advance Holdings Limited
Priority to CN2011800583550A priority patent/CN103269685A/zh
Priority to JP2013545397A priority patent/JP2014503542A/ja
Priority to EP11799722.1A priority patent/EP2654719A1/en
Priority to AU2011347257A priority patent/AU2011347257A1/en
Priority to NZ609742A priority patent/NZ609742A/en
Publication of WO2012085185A1 publication Critical patent/WO2012085185A1/en

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
    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/136—Amines having aromatic rings, e.g. ketamine, nortriptyline having the amino group directly attached to the aromatic ring, e.g. benzeneamine
    • 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
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the present invention relates to an aqueous solution, comprising an acid addition salt of ambroxol.
  • the aqueous solution of the present invention comprises an ambroxol content ranging from 0.1 % to 7% (w/v), a total content of polyalcohols selected from polyols and polyalkyleneglycols of at least 20% (w/v), an alcohol content lower than 1 % (w/v) and is free of benzoic acid and/or salts thereof with organic or inorganic bases, hereinbelow collectively referred to as "benzoates".
  • Ambroxol hydrochloride [trans-4-(2-amino-3,5-dibromobenzyl amino)cyclohexanol hydrochloride] (Ph. Eur., Monograph 1489) is a well known mucolytic drug available in various compositions suitable for oral or parenteral administration. However, oral compositions are by far preferred.
  • US2003/0171391 and US 2005/0014844 generally disclose a pharmaceutical composition containing ambroxol.
  • Example G of both such patent applications discloses an oral solution comprising 1 .5% w/v of ambroxol, 6% w/v of a sorbitol solution at 70%, 2% w/v of glycerol, and minor amount of other additives and flavouring agents.
  • US 2005/0266058, US 2003/01 13377, and US 2005/0075403 generally disclose a pharmaceutical composition containing ambroxol, in particular in the form of gels, hydrophilic pastes, lotions, solutions, suppositories, hydrophobic pastes, ointments, creams, lotions, sticks, lozenges, tablets, pastilles, and sweets.
  • Example 1 of US 2005/0266058 discloses an aqueous solution comprising 1 % w/w of ambroxol, 20% w/w of a glycerol solution at 85%, 5% w/w of ethanol solution at 96%, and minor amount of flavouring and colouring agents.
  • Examples 1 1 and 15 of US 2003/01 13377 disclose an aqueous solution comprising about 2.3% w/w of ambroxol, about 47% w/w of propylene glycol, and 10% w/w of ethanol.
  • Formulation 3 of US 2005/0075403 discloses an aqueous solution comprising 1 % w/w of ambroxol, 30% w/w of sorbitol, 10% w/w of glycerol, 5% w/w of ethanol, and minor amount of flavouring agents.
  • EP 1 543 826 describes an oral liquid formulation of ambroxol, characterized by high concentration (about 4-7% w/v) of the active ingredient.
  • Example 1 of EP 1 543 826 discloses an aqueous solution comprising 5% w/v of ambroxol, 20% w/v of xylitol, 10% w/v of Solutol HS15, 2.9% w/v of glycerol, 0.50% w/v of sodium benzoate, and minor amount of flavouring agents.
  • Such formulation is said to be stable for at least 12 months if it is stored in an amber glass bottle at 25 °C.
  • preservatives like alcohols, benzoates, sorbates, and parabens is common in liquid formulations. Preservatives are effective in controlling mold, inhibiting yeast growth and protecting against bacterial proliferation, thus, finally, to allow compliance with the European Pharmacopoeia microbiological specifications (Ph. Eur. 6.7, ⁇ 5.1 .4) for "aqueous preparations for oral use” or "aqueous preparations for oromucosal use”. The use of preservatives is particularly recommended in aqueous compositions, wherein microorganisms can find favourable conditions for their propagation.
  • impurity B trans-4-(6,8- dibromo-1 ,4-dihydroquinazolin-3(2H)-yl)cyclohexanol.
  • impurity A (2-amino-3,5-dibromophenyl)methanol]
  • impurity E (2-amino-3,5-dibromobenzaldeyde), but both can be controlled by operating in nitrogen atmosphere.
  • aqueous oral ambroxol formulations known in the art both with low and high active ingredient concentration, contain benzoates or other specific antimicrobial preservatives.
  • Benzoates are known to induce adverse reactions, both in adults and children, for example in asthmatic persons (see Petrus M. et al., Arch. Pediatr., 1996; 3(10): 984-7), fixed drug eruption (Vilaplana J. ei al., Contact Dermatitis, 2003; 49(6):290-1 ) and episodes of acute urticaria/angio-oedema. (Nettis E. et al., Br. J. Dermatol., 2004; 151 (4): 898-902). Further, recent studies have reported serious side effects associated with potassium sorbate and methyl hydroxybenzoate (methyl-paraben). Skin reactions, such as rash, urticaria, and contact dermatitis have been reported after topical application.
  • the Applicant has found that, despite the absence of sodium benzoate and the very low, if any, amount of alcohols, when the total content of polyols and polyalkyleneoxides is at least 20% w/v. the "efficacy of antimicrobial preservation" (Eur. Ph. 6.6 Ed. ⁇ 5.1 .3) test in different severe conditions is maintained, so that the presence of additional preservatives, together with the side effects thereof, can be optionally avoided.
  • an object of this invention to provide an aqueous solution comprising an acid addition salt of ambroxol, wherein the ambroxol content is ranging from 0.1 % to 7% (w/v), the total content of polyalcohols selected from polyols and/or polyalkyleneglycols is at least 20% (w/v), the total content of alcohols is lower than 1 % (w/v), and said aqueous solution is free of benzoates.
  • the term “benzoates” shall refer to both the benzoic acid and the salt thereof with organic or inorganic bases.
  • the term “free of” referred to the amount of “benzoates” as defined herein shall mean that the amount of benzoates is below 0.001 % (w/v).
  • alcohols shall refer to any of a class of pharmaceutically acceptable organic compounds bearing only one hydroxy (-OH) group attached to a carbon atom of an alkyl group (hydrocarbon chain). Specific examples of alcohols within the above mentioned definition are: ethanol, propanol and isopropanol.
  • the acid addition salt of ambroxol is hydrochloride salt.
  • the ambroxol content is from 0.2 to 6% (w/v), more preferably is from 0.3 to 5% (w/v), and most preferably from 1 .0% to 4.0% (w/v).
  • the formulation comprises polyalcohols selected from polyols and/or polyalkyleneglycols having solubilising, surfactant and sweetening properties as main functions.
  • said polyols are selected from glycols, such as ethylene glycol, propylene glycol, 1 ,3-propanediol, trimethylene glycol, 1 ,2- butanediol, 1 ,3-butanediol, 1 ,4-butanediol, 1 ,2-pentanediol, 1 ,4- pentanediol, 1 ,5-pentanediol, 1 ,6-hexanediol, 1 ,7-heptanediol, diethylene glycol, dipropylene glycol, glycerol, 1 , 1 , 1 -trimethylolpropane, 1 ,1 ,1 -trimethylolethane, 1 ,2,6 hexanetriol, etohexadiol, 2-methyl-2,4- pentanediol, 1 ,8-octanedi
  • the polyols useful in the present invention are selected from glycerol, propylene glycol, xylitol, sorbitol, sucrose, glucose, and mixture thereof.
  • said polyalkylene glycols are selected from polyethylene glycol, polypropylene glycol, esters thereof with organic acids, or ethers thereof with alcohols, and mixture thereof.
  • the polyalkylene glycols useful in the present invention are selected from esters of polyethylene glycols having a molecular weight ranging from 200 to 1500 (PEG 200, PEG 300, PEG 400, PEG 600, PEG 660, PEG 1000, PEG 1500) with hydroxy fatty acids, such as, for example hydroxylauric acid, hydroxymyristic acid, hydroxypalmitic acid, hydroxystearic acid, and hydroxyarachidic acid.
  • the polyalkylene glycol ester useful in the present invention is SolutolTM HS 15 (Macrogol 15 hydroxystearate, Ph. Eur., Monograph 2052), a polyethylene glycol 660 hydroxystearate manufactured by BASF (Parsippany, N.J.).
  • the total content of the above described polyols and polyalkylene glycols amounts to at least 20% by weight based on the total volume of the aqueous solution (w/v).
  • the total content of the above described polyols and polyalkylene glycols ranges from 25% to 75% w/v, more preferably from 30% to 70% w/v, and most preferably from 35% to 65% w/v.
  • the total content of alcohols is lower than 0.7% (w/v), and more particularly, the presence of alcohols can also be totally avoided.
  • the aqueous solution is preferably free of additional preservatives represented by sorbic acid, sorbates (salts of sorbic acid) and parabens (esters of para-hydroxybenzoic acid).
  • additional preservatives represented by sorbic acid, sorbates (salts of sorbic acid) and parabens (esters of para-hydroxybenzoic acid).
  • the term "free of” referred to the amount of "additional preservatives" as defined herein shall mean that the amount of any of such preservatives is below 0.001 % (w/v).
  • the pH value of the formulation is from 6 to 7 and more preferably it is about 6.4.
  • a pH value of from 6 to 7 is obtained by adding an inorganic or organic base, such as sodium or potassium hydroxide, sodium or potassium bicarbonate, triethanolamine, tris [tris(hydroxy methyl)aminomethane], N-methylglucosamine, lysine, arginine and the like.
  • an inorganic or organic base such as sodium or potassium hydroxide, sodium or potassium bicarbonate, triethanolamine, tris [tris(hydroxy methyl)aminomethane], N-methylglucosamine, lysine, arginine and the like.
  • the aqueous solution of this invention may comprise further pharmacologically active ingredients whose concurrent administration is useful, provided they do not interfere with the solubility of the acid addition salt of ambroxol in the solution of this invention.
  • an acid addition salt of ambroxol is the sole pharmacologically active ingredient in the aqueous solution of this invention.
  • the solution of this invention preferably comprises a taste masking agent.
  • the taste masking agent is an ammonium salt of glycyrrhizic acid.
  • the preferred salt is ammonium monoglycyrrhizinate.
  • ammonium monoglycyrrhizinate with menthol has been found to be particularly effective.
  • the preferred ammonium monoglycyrrhizinate:menthol weight ratio is of from 0.5:10 to 5:10.
  • the preferred ammonium monoglycyrrhizinate:ambroxol weight ratio is of from 0.001 :1 to 0.1 :1 . More preferably, said weight ratio is of from 0.01 :1 to 0.05:1 and even more preferably, it is of from 0.01 1 :1 to 0.025:1 .
  • the solution of this invention is suitable for mucolytic therapy in place of known ambroxol-based compositions. Moreover, the most concentrated (> 5%) solutions of this invention are also effective in the treatment of sore throat symptoms when administered in the form of sprays or mouth washes.
  • the solution of the present invention is for oral use.
  • Preferred dosage forms of the solution of this invention are, therefore, syrups, drops, sprays and mouthwashes.
  • the following examples further illustrate the invention, without limiting it.
  • Formulation 1 5% ambroxol solution, comparative formulation according to EP 1 543 826 (100 mL).
  • Formulation 2 5% ambroxol solution, formulation according to the present invention (100 mL).
  • a standard solution of impurity B was prepared by weighing exactly 10 mg of the product, in a 100 mL volumetric flask. The product was dissolved with acetonitrile and the solution thus obtained was brought to volume (100 mL) with acetonitrile.
  • a standard solution of ambroxol HCI was prepared by weighing exactly 50 mg of the product, in a 25 mL volumetric flask. The product was then dissolved with 10 mL of acetonitrile and then, 0.5 ml of the standard solution of impurity B, prepared as described above, was added. The solution thus obtained was brought to volume (25 ml_) with acetonitrile.
  • Two sample solutions were prepared for both Formulations 1 and 2.
  • the sample solutions to be used in the HPLC analysis were prepared by transferring 1 g of each Formulation 1 and Formulation 2, into two 25 ml_ volumetric flasks. The solutions thus obtained were brought to volume (25 ml_) with acetonitrile.
  • Accelerated stability tests are performed by storing a product in stress conditions.
  • the accelerated stability test in this case was performed according to the EMEA Guideline on Stability Testing (CPMP/QWP/122/02, rev 1 ), i.e. by maintaining the product in its container at a temperature of 40 °C ⁇ 2°C and 75% + 5 %RH (Relative Humidity) for six months.
  • Formulation 3 0.3% ambroxol solution, comparative formulation prepared in substantial agreement with that of Mucosolvan (100 ml_).
  • Formulation 4 0.3% ambroxol solution, as Formulation 3, modified according to the present invention (100 ml_). Table 4
  • Formulation A and B correspond to Formulations 2 and 4.
  • Formulation C has the composition of the following Table 7.
  • pH 6.4 Formulations A to C were subjected to a test to verify the preservative properties.
  • the test for efficacy of anti-microbial preservation was performed in accordance with the EU Ph. 6.6, ⁇ 5.1 .3.
  • the test verified that the limits related to the concentration of bacteria and fungi in oral preparations were in accordance with Table 5.1 .3-3 of the European Pharmacopoeia.
  • Formulations A to C demonstrated that the preservative properties of the preparations were maintained, although the absence of a specific excipient acting as preservative agent.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Compositions Of Macromolecular Compounds (AREA)
  • Chemical And Physical Treatments For Wood And The Like (AREA)
PCT/EP2011/073754 2010-12-23 2011-12-22 Aqueous solution of ambroxol WO2012085185A1 (en)

Priority Applications (10)

Application Number Priority Date Filing Date Title
NZ609742A NZ609742A (en) 2010-12-23 2011-12-22 Aqueous solution of ambroxol
MX2013005500A MX2013005500A (es) 2010-12-23 2011-12-22 Solucion acuosa de ambroxol.
CA2817453A CA2817453A1 (en) 2010-12-23 2011-12-22 Aqueous solution of ambroxol
EA201300535A EA201300535A1 (ru) 2010-12-23 2011-12-22 Водный раствор амброксола
BR112013012815A BR112013012815A2 (pt) 2010-12-23 2011-12-22 solução aquosa de ambroxol
KR1020137013725A KR20130140042A (ko) 2010-12-23 2011-12-22 암브록솔의 수용액
CN2011800583550A CN103269685A (zh) 2010-12-23 2011-12-22 氨溴索水溶液
JP2013545397A JP2014503542A (ja) 2010-12-23 2011-12-22 アンブロキソールの水溶液
EP11799722.1A EP2654719A1 (en) 2010-12-23 2011-12-22 Aqueous solution of ambroxol
AU2011347257A AU2011347257A1 (en) 2010-12-23 2011-12-22 Aqueous solution of ambroxol

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP10196711.5 2010-12-23
EP10196711 2010-12-23
US201061428269P 2010-12-30 2010-12-30
US61/428,269 2010-12-30

Publications (1)

Publication Number Publication Date
WO2012085185A1 true WO2012085185A1 (en) 2012-06-28

Family

ID=45094329

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2011/073754 WO2012085185A1 (en) 2010-12-23 2011-12-22 Aqueous solution of ambroxol

Country Status (13)

Country Link
EP (1) EP2654719A1 (pt)
JP (1) JP2014503542A (pt)
KR (1) KR20130140042A (pt)
CN (1) CN103269685A (pt)
AR (1) AR084537A1 (pt)
AU (1) AU2011347257A1 (pt)
BR (1) BR112013012815A2 (pt)
CA (1) CA2817453A1 (pt)
CL (1) CL2013001297A1 (pt)
EA (1) EA201300535A1 (pt)
MX (1) MX2013005500A (pt)
NZ (1) NZ609742A (pt)
WO (1) WO2012085185A1 (pt)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103462942A (zh) * 2013-08-20 2013-12-25 湖南赛隆药业有限公司 一种吸入用盐酸氨溴索溶液
CN104316482A (zh) * 2014-08-15 2015-01-28 河北菲尼斯生物技术有限公司 一种盐酸氨溴索颗粒的质量控制方法
CN113995721A (zh) * 2020-07-27 2022-02-01 德国吉麦医疗技术有限公司 一种盐酸氨溴索口腔喷雾溶液及其制备方法

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102083621B1 (ko) * 2013-06-13 2020-03-02 한미약품 주식회사 암브록솔 및 레보드로프로피진을 포함하는 안정성이 개선된 경구용 액상 제제
CN105287367B (zh) * 2015-10-13 2018-07-10 华润三九（南昌）药业有限公司 一种盐酸氨溴索的口服液体制剂及其制备方法与应用
CN109060473B (zh) * 2018-07-27 2021-03-05 商洛学院 一种盐酸氨溴索杂质对照品的制备方法
CN112168782A (zh) * 2020-10-26 2021-01-05 山东裕欣药业有限公司 一种呼吸系统药物口服喷雾剂的制备方法
CN112168783A (zh) * 2020-10-26 2021-01-05 山东裕欣药业有限公司 一种呼吸系统药物口服喷雾剂及制备方法
CN114129510A (zh) * 2021-12-03 2022-03-04 聊城大学 一种复方磺胺注射剂及制备方法

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0125634A1 (de) * 1983-05-13 1984-11-21 Reichert, Dietrich, Dr. med. Verwendung einer sekretolytisch wirkenden Substanz zur Herstellung eines Antischnarchmittels und zur Bekämpfung des Schnarchphänomens
WO2001005378A1 (de) 1999-07-20 2001-01-25 Boehringer Ingelheim International Gmbh Ambroxolhaltige lutschtablette
US20030113377A1 (en) 2001-10-10 2003-06-19 Dobrozsi Douglas Joseph Orally administered liquid compositions
US20030171391A1 (en) 2002-01-25 2003-09-11 Boehringer Ingelheim Pharma Gmbh & Co. Kg Ambroxol for the treatment of chronic pain
US20050014844A1 (en) 2003-07-16 2005-01-20 Boehringer Ingelheim International Gmbh Ambroxol for the treatment of acute pain
US20050075403A1 (en) 2003-10-02 2005-04-07 Boehringer Ingelheim Pharma Gmbh & Co. Kg Ambroxol for the treatment of inflammation in the pharynx
EP1543826A1 (en) 2003-12-16 2005-06-22 Advance Holdings Limited Concentrated aqueous solution of ambroxol
EP1543286A1 (de) 2002-08-30 2005-06-22 W.L. GORE & ASSOCIATES GmbH Infrarot reflektierendes abdeckmaterial
WO2005107732A1 (de) * 2004-05-03 2005-11-17 Boehringer Ingelheim International Gmbh Topische zubereitung enthaltend ambroxol

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000007561A (ja) * 1998-06-18 2000-01-11 Nissho Corp 塩酸アンブロキソール水溶液製剤
KR101232924B1 (ko) * 2003-09-09 2013-02-13 쓰리엠 이노베이티브 프로퍼티즈 컴파니 농축된 항균 조성물 및 방법
CN101961307B (zh) * 2010-09-14 2012-07-25 武汉人福药业有限责任公司 治疗呼吸道疾病的口服液及其制备方法

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0125634A1 (de) * 1983-05-13 1984-11-21 Reichert, Dietrich, Dr. med. Verwendung einer sekretolytisch wirkenden Substanz zur Herstellung eines Antischnarchmittels und zur Bekämpfung des Schnarchphänomens
WO2001005378A1 (de) 1999-07-20 2001-01-25 Boehringer Ingelheim International Gmbh Ambroxolhaltige lutschtablette
US20030113377A1 (en) 2001-10-10 2003-06-19 Dobrozsi Douglas Joseph Orally administered liquid compositions
US20030171391A1 (en) 2002-01-25 2003-09-11 Boehringer Ingelheim Pharma Gmbh & Co. Kg Ambroxol for the treatment of chronic pain
EP1543286A1 (de) 2002-08-30 2005-06-22 W.L. GORE & ASSOCIATES GmbH Infrarot reflektierendes abdeckmaterial
US20050014844A1 (en) 2003-07-16 2005-01-20 Boehringer Ingelheim International Gmbh Ambroxol for the treatment of acute pain
US20050075403A1 (en) 2003-10-02 2005-04-07 Boehringer Ingelheim Pharma Gmbh & Co. Kg Ambroxol for the treatment of inflammation in the pharynx
EP1543826A1 (en) 2003-12-16 2005-06-22 Advance Holdings Limited Concentrated aqueous solution of ambroxol
WO2005107732A1 (de) * 2004-05-03 2005-11-17 Boehringer Ingelheim International Gmbh Topische zubereitung enthaltend ambroxol
US20050266058A1 (en) 2004-05-03 2005-12-01 Boehringer Ingelheim International Gmbh Topical preparations containing ambroxol

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
C. BOUKARIM ET AL., THE JOURNAL OF APPLIED RESEARCH, vol. 9, no. 1, 2, 2009
DEUTSCHE, APOTHEKER ZEITUNG, vol. 17, 2002, pages 2113
J. FISCHER ET AL., ARZNEIM. FORSCH., vol. 52, 2002, pages 256
NETTIS E. ET AL., BR. J. DERMATOL., vol. 151, no. 4, 2004, pages 898 - 902
PETRUS M. ET AL., ARCH. PEDIATR., vol. 3, no. 10, 1996, pages 984 - 7
VILAPLANA J. ET AL., CONTACT DERMATITIS, vol. 49, no. 6, 2003, pages 290 - 1

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103462942A (zh) * 2013-08-20 2013-12-25 湖南赛隆药业有限公司 一种吸入用盐酸氨溴索溶液
CN104316482A (zh) * 2014-08-15 2015-01-28 河北菲尼斯生物技术有限公司 一种盐酸氨溴索颗粒的质量控制方法
CN113995721A (zh) * 2020-07-27 2022-02-01 德国吉麦医疗技术有限公司 一种盐酸氨溴索口腔喷雾溶液及其制备方法

Also Published As

Publication number Publication date
JP2014503542A (ja) 2014-02-13
KR20130140042A (ko) 2013-12-23
CL2013001297A1 (es) 2013-10-11
CA2817453A1 (en) 2012-06-28
NZ609742A (en) 2015-01-30
CN103269685A (zh) 2013-08-28
MX2013005500A (es) 2013-09-26
BR112013012815A2 (pt) 2016-09-13
AU2011347257A1 (en) 2013-05-23
AR084537A1 (es) 2013-05-22
EP2654719A1 (en) 2013-10-30
EA201300535A1 (ru) 2013-08-30

Similar Documents

Publication Publication Date Title
WO2012085185A1 (en) Aqueous solution of ambroxol
EP2170362B1 (en) Lyophilized anti-fungal composition
EP2647380B1 (en) Pharmaceutical composition including mometasone furoate and azelastine hydrochloride for nasal administration
EP1713466B1 (en) Antiparasitic composition containing an organic amine salt of closantel
JP6832281B2 (ja) バンコマイシンの水溶液製剤
US20160143911A1 (en) Stable and water soluble pharmaceutical compositions comprising pemetrexed
AU634271B2 (en) Stable solutions of mitomycin c
WO2011014541A1 (en) Stable formulations of azacitidine
EP1543826B1 (en) Concentrated aqueous solution of ambroxol
US8758782B2 (en) Excipient preservatives and pharmaceutical compositions comprised thereof
EP2804597B1 (en) Aqueous paracetamol composition for injection
WO2018184540A1 (zh) 包含组氨酸缓冲体系的英夫利西单抗组合物
AU2011254651B2 (en) Pharmaceutical aqueous compositions comprising lipoic acid as an antioxidant
EP2695605A1 (en) Tranexamic acid composition
AU2011254651A1 (en) Pharmaceutical aqueous compositions comprising lipoic acid as an antioxidant
US20080312304A1 (en) Topical compositions containing metronidazole
US20080076798A1 (en) Alcohol free formulation of argatroban
CA3101093A1 (en) Dantrolene formulations and methods of their use
WO2014032956A1 (en) Tigecycline formulations
US20080287514A1 (en) Topical compositions containing metronidazole
US20140275122A1 (en) Voriconazole Formulations
WO2017037232A1 (en) Anidulafungin formulations
US20240180935A1 (en) Solution formulation of cyclophosphamide
JP2012224629A (ja) ペミロラストを含有する安定な水性組成物
EP1551391B1 (en) Dry syrup preparation of procaterol comprising ascorbic acid and citric acid

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 11799722

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2011799722

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2817453

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 2013001297

Country of ref document: CL

WWE Wipo information: entry into national phase

Ref document number: MX/A/2013/005500

Country of ref document: MX

ENP Entry into the national phase

Ref document number: 2011347257

Country of ref document: AU

Date of ref document: 20111222

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 20137013725

Country of ref document: KR

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2013545397

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 201300535

Country of ref document: EA

NENP Non-entry into the national phase

Ref country code: DE

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112013012815

Country of ref document: BR

ENP Entry into the national phase

Ref document number: 112013012815

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20130523