CN1652763A - 用于局部治疗口咽腔疾病的基于双氯芬酸的组合物 - Google Patents

用于局部治疗口咽腔疾病的基于双氯芬酸的组合物 Download PDF

Info

Publication number
CN1652763A
CN1652763A CNA038105764A CN03810576A CN1652763A CN 1652763 A CN1652763 A CN 1652763A CN A038105764 A CNA038105764 A CN A038105764A CN 03810576 A CN03810576 A CN 03810576A CN 1652763 A CN1652763 A CN 1652763A
Authority
CN
China
Prior art keywords
compositions
diclofenac
salt
topical treatment
oropharyngeal cavity
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.)
Granted
Application number
CNA038105764A
Other languages
English (en)
Other versions
CN1303992C (zh
Inventor
M·平扎
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Angelini Ricerche SpA
Angelini Acraf SpA
Original Assignee
Aziende Chimiche Riunite Angelini Francesco ACRAF SpA
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
Application filed by Aziende Chimiche Riunite Angelini Francesco ACRAF SpA filed Critical Aziende Chimiche Riunite Angelini Francesco ACRAF SpA
Publication of CN1652763A publication Critical patent/CN1652763A/zh
Application granted granted Critical
Publication of CN1303992C publication Critical patent/CN1303992C/zh
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • 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
    • A61P11/02—Nasal agents, e.g. decongestants
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02—Local antiseptics

Landscapes

  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Rheumatology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Otolaryngology (AREA)
  • Pulmonology (AREA)
  • Pain & Pain Management (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Cosmetics (AREA)

Abstract

本发明涉及用于局部治疗口咽腔疾病的组合物，其包含双氯芬酸与氨丁三醇的盐的水溶液，其中所述盐的量为0.1％至0.2％(w/w)且将pH调为7至8。

Description

用于局部治疗口咽腔疾病的基于双氯芬酸的组合物
本发明涉及用于局部治疗口咽腔疾病的基于双氯芬酸的组合物。
已知双氯芬酸[2-(2，6-二氯苯胺基)苯乙酸]是一种广泛使用的药物产品，具有抗炎、解热和镇痛性质。它主要以原形或以其与无机或有机碱的盐形式全身施用。
但是，它的盐几乎不溶于水。
专利US-4 407 824的实施例2描述了双氯芬酸与氨丁三醇[三(羟甲基)甲胺]的盐的制备，但没有详细说明其在水中的溶解度，并且未给出任何含有上述盐的药物形式的实例。
在EP-A-0 521 393中也确认了双氯芬酸盐不溶于水的问题，其建议用胆碱盐解决所述问题。据描述，该盐是可令人惊讶地溶于水且还特别适于制备漱口剂的化合物。
但是，胆碱盐具有胆碱的典型缺点，即众所周知的其令人不愉快的气味和味道。
对于需要与粘膜保持接触较长时间以发挥其治疗作用、用于局部治疗口咽腔疾病的组合物，例如漱口剂和口腔喷雾剂，这些缺点特别不利。
即使加入大量能掩盖其味道的成分[0.5％(w/w)的乙酰舒泛和35％(w/w)的山梨醇]，用于局部治疗口咽腔疾病的基于双氯芬酸与胆碱的盐的组合物仍然口味较差。
因此，仍然非常需要用于局部治疗口咽腔疾病、具有令人愉快或者至少是中性味道的基于双氯芬酸的组合物。
尽管A.Fini等人已经报道说认为氨丁三醇盐在水中的溶解度为0.167g/100ml(European J.Pharm.Sci.4，231，1996)，但本发明人所进行的试验已证明：即使在化学计算量(分别为0.029至0.058g)的氨丁三醇存在下，量为0.071至0.142g的双氯芬酸也不能溶于100ml水(对比实施例1和2)。
令人惊讶的是，现已发现：如果将它们的pH调至7-8，则含有0.071至0.142g双氯芬酸与化学计算量(分别为0.029至0.058g)氨丁三醇的上述组合物在100ml水中变得澄明且长时间保持澄明(实施例1和2)。
同样令人惊讶的是，已发现：这些溶液的口味良好，并且也可非常容易地用中等量的标准矫味剂和甜味剂来改善口味。
因此，本发明的一项主题是用于局部治疗口咽腔疾病的组合物，其特征在于：其包含双氯芬酸与氨丁三醇的盐的水溶液，其中所述盐的量为0.1％至0.2％(w/w)且将pH调为7至8。
在本发明的组合物中，双氯芬酸与氨丁三醇的盐的优选浓度为0.1％(w/w)。
有利地，上述漱口剂包含其它标准成分，例如乙醇、多羟基醇、络合剂、防腐剂、湿润剂、甜味剂、矫味剂、着色剂等。
这些成分的典型例子有：
多羟基醇：甘油、丙二醇和聚乙二醇；
络合剂：依地酸钠；
防腐剂：对羟基苯甲酸甲酯和对羟基苯甲酸丙酯、苯甲酸钠；
湿润剂：甘油聚乙二醇蓖麻醇酸酯(glyceryl polyethylene glycolricinoleate)；
甜味剂：糖精钠、山梨醇、乙酰舒泛和木糖醇；
胶凝剂：聚乙二醇和聚丙二醇嵌段共聚物，例如PoloxamerTM407；
矫味剂：薄荷矫味剂、天然什锦果味矫味剂和石榴汁矫味剂；
着色剂：喹啉黄E 104和专利蓝E 131。
用本发明的组合物进行治疗可受益的口咽腔疾病的典型例子有：由放射治疗和化学治疗引起的龈炎、舌炎、口炎、口疮、牙周病、牙周炎、喉炎、咽炎和粘膜炎。另外，本发明的组合物可用于治疗牙外科手术和/或普通外科手术的后遗效应。
本发明组合物的优选剂型是漱口剂和口腔喷雾剂。
根据药物化学工作者已知的技术可容易地制备这些剂型，包括如混合、溶解、灭菌等步骤。
以下实施例用于举例说明本发明，但不限制本发明。
                           实施例1
                           漱口剂A
100g漱口剂A含有：
双氯芬酸与氨丁三醇的盐*           0.104g
木糖醇                             10.000g
PoloxamerTM407                    0.500g
苯甲酸钠                           0.500g
天然薄荷矫味剂                     0.500ml
E 131水溶液(1mg/ml)                0.200ml
pH7.8的磷酸盐缓冲液**适量至       100g
pH                                 7.6
*等于0.074g双氯芬酸
**1升在纯化水中的溶液含有：无水磷酸氢二钠(5.803g)、无水磷酸二氢钾(3.522g)和1N氢氧化钠(18.70ml)。
                           实施例2
                           漱口剂B
除以下区别外，100g漱口剂B具有与漱口剂A相同的组成：
-其还含有天然什锦果味矫味剂(0.04ml)和天然石榴汁矫味剂(0.02ml)，和
-其含有0.25ml E 124水溶液(10mg/ml)，用于代替0.2ml E 131水溶液(1mg/ml)。
                         对比实施例1
                           漱口剂C
制备除含有纯化水代替pH7.8的磷酸盐缓冲液之外与漱口剂A组成相同的漱口剂。
                         对比实施例2
                           漱口剂D
制备除含有纯化水代替pH7.8的磷酸盐缓冲液之外与漱口剂B组成相同的漱口剂。
                           稳定性
发现漱口剂A和B稳定。
相反，漱口剂C和D尤其是在冷的条件下在一段时间中释放双氯芬酸沉淀。
对于所含有的双氯芬酸与氨丁三醇的盐的量低于(以上所引用的)Fini等人报道的溶解度限度的漱口剂，该现象是完全出乎意料的。

Claims (8)

1.用于局部治疗口咽腔疾病的组合物，其特征在于：其包含双氯芬酸与氨丁三醇的盐的水溶液，其中所述盐的量为0.1％至0.2％(w/w)且将pH调为7至8。
2.根据权利要求1的组合物，其特征在于：其含有0.10％(w/w)的双氯芬酸与氨丁三醇的盐。
3.根据权利要求1或2的组合物，其特征在于：其还包含选自糖精钠、山梨醇、乙酰舒泛和木糖醇的甜味剂。
4.根据以上权利要求1至3中任一项的组合物，其特征在于：其还包含选自苯甲酸钠、对羟基苯甲酸甲酯和对羟基苯甲酸丙酯的防腐剂。
5.根据以上权利要求1至4中任一项的组合物，其特征在于：其还包含由聚乙二醇和聚丙二醇嵌段共聚物组成的胶凝剂。
6.根据以上权利要求1至5中任一项的组合物，其特征在于：其还包含可药用的矫味剂。
7.根据以上权利要求1至6中任一项的组合物，其特征在于：其还包含可药用的着色剂。
8.根据以上权利要求1至7中任一项的组合物，其特征在于：其用于治疗由放射治疗和化学治疗引起的龈炎、舌炎、口炎、口疮、牙周病、牙周炎、喉炎、咽炎、口腔粘膜炎，以及牙外科手术和/或普通外科手术的后遗效应。
CNB038105764A 2002-05-10 2003-04-16 用于局部治疗口咽腔疾病的基于双氯芬酸的组合物 Expired - Fee Related CN1303992C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT2002MI000986A ITMI20020986A1 (it) 2002-05-10 2002-05-10 Composizione a base di diclofenac per il trattamento topico di affezioni del cavo orofaringeo
ITMI02A000986 2002-05-10

Publications (2)

Publication Number Publication Date
CN1652763A true CN1652763A (zh) 2005-08-10
CN1303992C CN1303992C (zh) 2007-03-14

Family

ID=11449862

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB038105764A Expired - Fee Related CN1303992C (zh) 2002-05-10 2003-04-16 用于局部治疗口咽腔疾病的基于双氯芬酸的组合物

Country Status (22)

Country Link
US (1) US20050100597A1 (zh)
EP (1) EP1503747B1 (zh)
JP (1) JP2005526120A (zh)
KR (1) KR20040111415A (zh)
CN (1) CN1303992C (zh)
AR (1) AR039977A1 (zh)
AT (1) ATE333872T1 (zh)
AU (1) AU2003232480B2 (zh)
CA (1) CA2477773C (zh)
DE (1) DE60307086T2 (zh)
DK (1) DK1503747T3 (zh)
EA (1) EA006165B1 (zh)
ES (1) ES2268402T3 (zh)
GE (1) GEP20063822B (zh)
HK (1) HK1071312A1 (zh)
IL (2) IL163871A0 (zh)
IT (1) ITMI20020986A1 (zh)
MX (1) MXPA04010401A (zh)
PL (1) PL215221B1 (zh)
PT (1) PT1503747E (zh)
UA (1) UA79110C2 (zh)
WO (1) WO2003094905A1 (zh)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101138544B (zh) * 2006-09-06 2010-09-29 上海医药工业研究院 双氯芬酸或其盐局部成膜凝胶组合物及其应用
CN102538083A (zh) * 2010-12-29 2012-07-04 Lg电子株式会社 用于空调器的室外单元
CN104546527A (zh) * 2014-12-29 2015-04-29 福建省闽东力捷迅药业有限公司 一种含七叶皂苷钠的漱口液及其制备方法

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20032523A1 (it) 2003-12-19 2005-06-20 Acraf Forma di dosaggio per uso orale comprendente un farmaco
ITMI20040235A1 (it) * 2004-02-13 2004-05-13 Therapicon Srl Preparazione farmaceutica per il cavo orale
JP5432716B2 (ja) 2006-10-17 2014-03-05 ヌーボ リサーチ インコーポレイテッド ジクロフェナクゲル
US8618164B2 (en) 2009-03-31 2013-12-31 Nuvo Research Inc. Treatment of pain with topical diclofenac compounds
US8546450B1 (en) 2009-03-31 2013-10-01 Nuvo Research Inc. Treatment of pain with topical diclofenac compounds
US20120003162A1 (en) * 2010-06-30 2012-01-05 Mcneil-Ppc, Inc. Methods of Preparing Non-Alcohol Bioactive Esential Oil Mouth Rinses
DE102011111944A1 (de) * 2011-08-29 2013-02-28 Richard A. Huthmacher Verwendung von Diclofenac zur Verhinderung und Behandlung grippaler Infekte sowie durch grippale Infekte bewirkter Krankheitssymtome
US20150374745A1 (en) * 2014-06-30 2015-12-31 Mitochondrial Substrate Invention Limited Nutrients solutions for enhancement of cognitive function

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AT370721B (de) * 1981-02-24 1983-04-25 Ciba Geigy Ag Verfahren zur herstellung von neuen salzen der 2- (2,6-dichloranilino)-phenylessigsaeure, der
EP0373103B1 (de) * 1988-11-10 1993-03-31 Ciba-Geigy Ag Flüssige orale Formulierung
CA1340994C (en) * 1989-09-21 2000-05-16 Rudolf Edgar Dr. Falk Treatment of conditions and disease
US5028413A (en) * 1990-03-21 1991-07-02 Bausch & Lomb Incorporated Novel fluoride-containing dentifrice
IT1243342B (it) * 1990-07-13 1994-06-10 Farcon Ag Composizioni farmaceutiche orali liquide ad attivita' antiinfiammatoria
US5972906A (en) * 1991-07-03 1999-10-26 Hyal Pharmaceutical Corporation Treatment of mucous membrane disease, trauma or condition and for the relief of pain thereof
IT1250636B (it) * 1991-07-04 1995-04-21 Ricerche Di Schiena Del Dr Mic Sale del diclofenac, metodo di preparazione e composizioni farmaceutiche che lo contengono.
US5626838A (en) * 1995-03-13 1997-05-06 The Procter & Gamble Company Use of ketorolac for treatment of squamous cell carcinomas of the oral cavity or oropharynx
CN1059797C (zh) * 1995-11-22 2000-12-27 王树力 双氯芬酸钠喷雾剂

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101138544B (zh) * 2006-09-06 2010-09-29 上海医药工业研究院 双氯芬酸或其盐局部成膜凝胶组合物及其应用
CN102538083A (zh) * 2010-12-29 2012-07-04 Lg电子株式会社 用于空调器的室外单元
US8950208B2 (en) 2010-12-29 2015-02-10 Lg Electronics Inc. Outdoor unit for air conditioner
CN102538083B (zh) * 2010-12-29 2015-04-01 Lg电子株式会社 用于空调器的室外单元
CN104546527A (zh) * 2014-12-29 2015-04-29 福建省闽东力捷迅药业有限公司 一种含七叶皂苷钠的漱口液及其制备方法

Also Published As

Publication number Publication date
EA006165B1 (ru) 2005-10-27
ITMI20020986A0 (it) 2002-05-10
UA79110C2 (en) 2007-05-25
PT1503747E (pt) 2006-11-30
CN1303992C (zh) 2007-03-14
AU2003232480A1 (en) 2003-11-11
JP2005526120A (ja) 2005-09-02
ATE333872T1 (de) 2006-08-15
US20050100597A1 (en) 2005-05-12
DE60307086D1 (de) 2006-09-07
MXPA04010401A (es) 2005-02-17
HK1071312A1 (en) 2005-07-15
PL371426A1 (en) 2005-06-13
DK1503747T3 (da) 2006-11-27
ITMI20020986A1 (it) 2003-11-10
ES2268402T3 (es) 2007-03-16
IL163871A (en) 2007-10-31
EP1503747B1 (en) 2006-07-26
AR039977A1 (es) 2005-03-09
WO2003094905A1 (en) 2003-11-20
CA2477773C (en) 2011-01-18
IL163871A0 (en) 2005-12-18
EA200401090A1 (ru) 2005-02-24
EP1503747A1 (en) 2005-02-09
DE60307086T2 (de) 2007-02-01
PL215221B1 (pl) 2013-11-29
GEP20063822B (en) 2006-05-10
KR20040111415A (ko) 2004-12-31
CA2477773A1 (en) 2003-11-20
AU2003232480B2 (en) 2008-07-31
WO2003094905A8 (en) 2004-04-01

Similar Documents

Publication Publication Date Title
CN1303992C (zh) 用于局部治疗口咽腔疾病的基于双氯芬酸的组合物
CN1140411A (zh) 含有帕罗西汀树脂酸盐的口服液体组合物
EP1782816B1 (en) Water-based medicinal composition containing azithromycin and method of preparing the same
KR19980064024A (ko) 약학 조성물
WO1997007794A1 (fr) Composition pour anesthesie locale
EP0101178A2 (en) Topical anti-inflammatory compositions
JP2005510510A (ja) ２−（４−イソブチルフェニル）プロピオン酸の医薬組成物
JP2023540149A (ja) 抗ウイルス化合物の製剤
EP0877600A1 (en) Preservative systems for pharmaceutical compositions containing cyclodextrins
US5100898A (en) Antitussive liquid compositions containing dyclonine
ES2323264T3 (es) Composicion para enmascaramiento del sabor.
US4892877A (en) Antitussive liquid compositions containing phenol
EP1002531A1 (en) A water-miscible composition of non-steroidal antiinflammatory drugs
CA2362772C (en) Pharmaceutical formulation for intraveous or intramuscular octreotide administration
US20070154497A1 (en) Stable, palatable syrup containing ibuprofen and method of its preparation
CN1893922A (zh) 包括非甾体抗炎药,并且具有良好可口性的药物口服剂型
JP2003509474A (ja) 局所的薬学的組成物の抗菌効果を増強させるための脂肪酸／アミノ酸石鹸の使用
CN1224351A (zh) 含有尼美舒利的经口给药的药用制剂
US20050037979A1 (en) Tannate compositions and methods of use
KR20060031689A (ko) 피리베딜의 경비 투여용 약제 조성물
EP1041984A1 (fr) Composition pharmaceutique buvable
RU2002128741A (ru) Тимолсодержащая композиция, полезная для лечения устойчивых к лекарственным средствам бактериальных инфекций
JP2003183170A (ja) うがい剤

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20070314

Termination date: 20180416

CF01 Termination of patent right due to non-payment of annual fee