WO2005113492A1 - Sels d'ambroxol analogues de cysteine, procedes d'elaboration et utilisations - Google Patents

Sels d'ambroxol analogues de cysteine, procedes d'elaboration et utilisations Download PDF

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Publication number
WO2005113492A1
WO2005113492A1 PCT/CN2005/000685 CN2005000685W WO2005113492A1 WO 2005113492 A1 WO2005113492 A1 WO 2005113492A1 CN 2005000685 W CN2005000685 W CN 2005000685W WO 2005113492 A1 WO2005113492 A1 WO 2005113492A1
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Prior art keywords
ambroxol
water
cysteine
preparation
solvent
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PCT/CN2005/000685
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English (en)
Chinese (zh)
Inventor
Junda Cen
Huijuan Zhong
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Jiangsu Hansen Pharmaceutical Co., Ltd.
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Publication of WO2005113492A1 publication Critical patent/WO2005113492A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/42—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having amino groups or hydroxy groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C215/44—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having amino groups or hydroxy groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton bound to carbon atoms of the same ring or condensed ring system
    • 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
    • A61P11/10—Expectorants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/57—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C323/58—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton
    • C07C323/59—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton with acylated amino groups bound to the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/30—Hetero atoms other than halogen
    • C07D333/36—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Definitions

  • the invention relates to an ambroxol cysteine analog salt and a preparation method thereof, a pharmaceutical composition containing a pharmaceutically effective dose of the compound, and an application thereof for preparing an expectorant pharmaceutical preparation.
  • Ambroxol is the active metabolite of bromhexine. Its chemical name is trans-4-[(2-amino-3,5-dibromobenzyl) amino] cyclohexanol. Phlegm medicine has low toxicity and exact effect. Its expectorant effect is stronger than that of bromhexine. Its preparation method and pharmacological effect have been published in US Patent No. 3536713. Its clinical application has been published in Respiration 51 Suppl. 1,37 (1987). Ambroxol hydrochloride has been widely used in many countries such as the United States, Britain, Germany, Japan and other countries to treat respiratory diseases with excellent clinical effects and almost no toxic side effects.
  • this product can regulate the secretion of serous fluid and mucus, promote the synthesis of surface living substances in the lungs, strengthen the ciliary swing (increasing the clearing capacity of the mucous ciliary transport system), and make sputum easier.
  • the product can also increase the amount of fluid in the respiratory tract, reduce mucus secretion, promote the secretion of pulmonary surfactant and bronchial cilia movement, and make sputum easy to cough.
  • Ambroxol hydrochloride can improve lung function indicators and prevent respiratory infections.
  • Ambroxol hydrochloride is widely used clinically for acute and chronic respiratory diseases with abnormal sputum secretion and poor sputum excretion, such as acute and chronic bronchitis, asthma-type bronchitis, bronchiectasis and tracheal asthma, and surgery for patients undergoing lung surgery.
  • acute and chronic bronchitis asthma-type bronchitis
  • bronchiectasis tracheal asthma
  • tracheal asthma tracheal asthma
  • IRDS respiratory distress syndrome
  • Ambroxol hydrochloride is quickly absorbed orally and its elimination half-life is 2 ⁇ 3hr. Its preparations mainly include tablets, sustained-release pellets, solutions, syrups, water injections and other compound preparations. It is too ideal, which limits its application and clinical application.
  • the present invention surprisingly discovered through research that the new compound of ambroxol and acetylcysteine or erdosteine has a strong expectorant effect, and its expectorant effect is significantly stronger than that of a single compound. This constitutes the present invention.
  • the purpose of the present invention is to prepare an ambroxol cysteine analog salt with better curative effect, and overcome the shortcomings of the clinical curative effect and treatment scope of the existing preparation. Summary of the invention
  • An object of the present invention is to provide an ambroxol cysteine analogue having the following structure:
  • cysteine analogs include N-acetyl-L-cysteine and Erdostan.
  • N-acetyl-L-cysteine (Acetylcysteine, chemical name N-acetyl-L-cysteine) and Erdosteine (chemical name N- [2- (carboxymethylsulfanyl) ) Acetyl] homocysteine thiolactone) are two cysteine analogs currently available for expectoration, and their preparation methods and pharmacological effects have been published in US patents 3184505 and US4411909 Its clinical applications have been published in the literature N. Engl. J. Med. 319, 1557 (1988) and Thorax 43, 585 (1988). N-acetylcysteine (NAC) is a long-known compound.
  • NAC is usually administered topically or orally in the form of granules or tablets.
  • Erdostan is a new bronchitis expectorant. It was first marketed in France in 1995, and subsequently listed in European countries such as Switzerland, Italy, and the United Kingdom. It is used to treat chronic obstructive bronchitis, including acute bronchitis. Aggravated infectivity. This product has good anti-phlegm effect and free radical scavenging activity, and has an inhibitory effect on free radicals generated by smokers. Erdostan's clinical research on patients with chronic obstructive pulmonary disease has shown that this product has good efficacy and tolerance.
  • Erdostan can improve the efficacy of antibiotics (such as ampicillin) in the treatment of acute infections of bronchitis, greatly reduce the amount of antibiotics, and shorten the treatment time.
  • antibiotics such as ampicillin
  • Erdosteine has fewer adverse reactions. Due to its chemically protected thiol group, it is metabolized by the liver to become a free radical, which exerts antiphlegm, cough and scavenging free radical activities, and reduces gastrointestinal side effects.
  • the new compound of ambroxol and acetylcysteine or erdosteine has a strong expectorant effect, and its expectorant effect is significantly stronger than that of a single compound.
  • the present invention relates not only to the salt formed by ambroxol base and a single-molecule cysteine analog, but also to the salt formed by ambroxol base and a bi-molecular cysteine analog.
  • the salts mentioned here include crystals with specific structures and physicochemical properties, as well as amorphous solid powders or lyophilized powders; they can be used in the preparation of various commonly used dosage forms.
  • Another object of the present invention is to provide a method for preparing ambroxol cysteine analog salt.
  • the preparation method is a salt forming reaction of ambroxol and a cysteine analog in a solvent, and then using a concentration method, crystallization of a mixed solvent, crystal form conversion, filtration or freeze drying to obtain ambroxol White crystalline or lyophilized powder of cystine analog salt.
  • the mixed solvent refers to a water-soluble organic solvent.
  • Water-soluble organic solvents refer to lower alcohols, acetone, etc .; more Lower alcohols are preferred.
  • Lower alcohols are methanol, ethanol, propanol or isopropanol.
  • the above water-soluble solvents include lower alcohols, acetone and the like, and lower alcohols are preferred.
  • Lower alcohols include methanol, ethanol, propanol, and isopropanol.
  • the mixed solvent refers to a mixture of a water-soluble solvent and a non-water-soluble solvent.
  • the water-insoluble solvent includes a halocarbon-based solvent and an ether-based solvent, and chloroform, dichloromethane, ether, isopropyl ether, and the like are preferred.
  • the present invention also provides a pharmaceutical composition containing a therapeutically effective dose of the aforementioned structural ambroxol cysteine analogue salt as an active ingredient and a pharmaceutically acceptable carrier, excipient, or diluent such as a pharmaceutical auxiliary Agent.
  • the pharmaceutical composition is prepared by mixing the ambroxol cysteine analog salt prepared by the above method with a pharmaceutically acceptable pharmaceutical adjuvant, and then preparing the required preparation form according to the conventional preparation method of the preparation.
  • the composition may be in the form of tablets, capsules, powders, granules, lozenges, suppositories, or liquid formulations such as oral liquids or sterile parenteral solutions for oral or parenteral administration, and the route, dosage, and administration The number of times can be adjusted according to the patient's age, weight and disease.
  • the composition may also be in the form of a large or small volume injection, a lyophilized powder injection, a sterile powder portion, and the like.
  • Single-dose representations for oral administration may be tablets and capsules, and may contain conventional excipients such as binders, such as syrup, acacia, gelatin, sorbitol, tragacanth or polyvinylpyrrolidone; filling Agents such as lactose, sugar, corn starch, calcium phosphate, sorbitol or glycine; tabletting lubricants such as magnesium stearate; disintegrants such as starch, polyvinylpyrrolidone, sodium starch glycolate or microcrystalline cellulose; Or a pharmaceutically acceptable wetting agent, such as sodium lauryl sulfate.
  • binders such as syrup, acacia, gelatin, sorbitol, tragacanth or polyvinylpyrrolidone
  • filling Agents such as lactose, sugar, corn starch, calcium phosphate, sorbitol or glycine
  • tabletting lubricants such as magnesium stearate
  • disintegrants such
  • Solid oral compositions can be prepared by conventional mixing, filling or tabletting methods. Repeated blending operations can be used to distribute the active agent sufficiently into a composition using a large amount of filler. Such operations are of course routine in the art.
  • the tablets can be made into coated or plain tablets according to a conventional method.
  • Oral liquid preparations can be in the form of, for example, emulsions, syrups, or elixirs, or they can be present as dry products and reconstituted with water or other suitable carriers before use.
  • This liquid formulation may contain conventional additives such as suspending agents such as sorbitol, syrup, methyl cellulose, gelatin, hydroxyethyl cellulose, carboxymethyl cellulose, aluminum stearate gel or hydrogenated Edible fats; emulsifiers, such as lecithin, sorbitan monooleate, or gum arabic; anhydrous carriers (including edible oils), such as almond oil, distilled coconut oil, or oily esters, such oily esters include Glycerides, propylene glycol or ethanol; preservatives such as methyl or propyl parabens or sorbic acid; if desired, conventional flavoring or coloring agents can also be added.
  • suspending agents such as sorbitol, syrup, methyl cellulose, gelatin, hydroxyethyl
  • the active ingredient can be dissolved in a sterile carrier to prepare a unit liquid dosage form.
  • a sterile carrier When preparing a solution, the active ingredient can be dissolved in water for injection and filtered for sterilization, and then poured into a vial or ampoule and sealed.
  • adjuvants such as a local anesthetic, preservatives and buffering agents can be dissolved in the carrier.
  • the composition can be frozen and filled into vials, and the water can be removed under vacuum.
  • a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound.
  • the pharmaceutical composition can also be made into a sustained-release preparation according to a conventional method, such as a sustained-release pellet or a controlled-release pellet.
  • Another object of the present invention is to provide the application of ambroxol cysteine analog salt or a combination thereof in the preparation of a medicine for expectoration, and the use in the preparation of a pharmaceutical preparation.
  • Ambroxostatin, microcrystalline cellulose and lactose were sieved and mixed well, mixed with water to make a soft material, granulated through a 20-mesh sieve, wet granules were dried at 55-60 ° C, and dried granules were dried. A 20 mesh sieve is used to granulate, mix with magnesium stearate and fine powder silica gel, and fill the capsules.
  • Example 10 Preparation of ambroxol acetylcysteine oral solution
  • Citric acid 1. 5g
  • the microcrystalline cellulose, lactose, and ambroxol cysteine were pulverized through an 80-mesh sieve in advance and mixed uniformly.
  • the aqueous hydroxypropyl methylcellulose aqueous solution was used as a binder to prepare pellets, which were then mixed at 50 to 60 ° C dry, choose 20 ⁇ 30 mesh pellets and set aside.
  • the prepared and selected pellets are fluidized In the bed, the spray bag method is adopted to suspend fluidization through hot air. When the inlet air temperature is 55 ° C and the bed temperature is controlled at 30 ° C, the speed of the peristaltic pump is adjusted to supply liquid. The atomization pressure is 2 bar. The pellets are continuously sprayed.
  • mice 160 male mice were randomly divided into 15 groups, which were negative control groups, low, medium and high dose groups of ambroxol hydrochloride, low, medium and high dose groups of acetylcysteine, low, medium and high doses of erdosteine High-dose group, low, medium, and high-dose ambroxol acetylcysteine salt, low, medium, and high-dose group of ambroxoedostat salt, oral test sample once a day for 3 consecutive days, The administration volume was 0.4ml, and the negative control group received the same volume of saline.

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

Abstract

L'invention concerne des sels d'ambroxol analogues de cystéine de formule (I) ; n vaut 1 ou 2, A est tel que défini dans la description. On décrit aussi des procédés d'élaboration correspondants, des compositions pharmaceutiques renfermant ces produits, et des utilisations correspondantes pour la préparation d'expectorant. Les procédés consistent à faire réagir l'ambroxol et les analogues de cystéine dans un solvant et à conduire ensuite une cristallisation.
PCT/CN2005/000685 2004-05-20 2005-05-18 Sels d'ambroxol analogues de cysteine, procedes d'elaboration et utilisations WO2005113492A1 (fr)

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CN200410042363.8 2004-05-20
CNB2004100423638A CN1303065C (zh) 2004-05-20 2004-05-20 氨溴索半胱氨酸类似物盐及其制备方法和用途

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104922079A (zh) * 2015-05-26 2015-09-23 苗怡文 一种祛痰的药物盐酸氨溴索冻干粉针剂组合物
CN104971057A (zh) * 2015-08-05 2015-10-14 青岛蓝盛洋医药生物科技有限责任公司 一种治疗呼吸系统疾病的药物盐酸氨溴索组合物胶囊
CN105012245A (zh) * 2015-08-10 2015-11-04 青岛蓝盛洋医药生物科技有限责任公司 一种化痰药物盐酸氨溴索组合物颗粒剂及其制备方法
CN105055321A (zh) * 2015-09-01 2015-11-18 青岛蓝盛洋医药生物科技有限责任公司 一种治疗咳嗽的药物盐酸氨溴索组合物干混悬剂
CN105997902A (zh) * 2015-05-15 2016-10-12 苗怡文 一种治疗呼吸系统疾病的药物盐酸氨溴索组合物
CN106220518A (zh) * 2015-05-15 2016-12-14 苗怡文 一种制备治疗呼吸系统疾病的盐酸氨溴索化合物晶体的方法

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WO2008144956A1 (fr) * 2007-05-28 2008-12-04 Tianjin Institute Of Pharmaceutical Research Nouveaux composés ambroxol, leurs procédés de préparation et leurs utilisations
CN101544572B (zh) * 2008-03-26 2013-03-20 连云港恒邦医药科技有限公司 一种氨溴索衍生物及其制备方法
CN106220604A (zh) * 2015-04-30 2016-12-14 苗怡文 一种制备治疗呼吸道炎症的厄多司坦化合物的方法
CN112745251B (zh) 2019-10-31 2023-10-27 华创合成制药股份有限公司 一种治疗祛痰化合物及其制备方法和用途

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4845114A (en) * 1987-01-07 1989-07-04 Erregierre Industria Chimica Spa N-(trans-p-hydroxy-cyclohexyl)-(2-amino-3,5-dibromo)benzylamine salts possessing mucolytic activity

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ZA963590B (en) * 1995-05-10 1996-11-19 Adcock Ingram Ltd Pharmaceutical composition
JPH08337532A (ja) * 1995-06-14 1996-12-24 Takeda Chem Ind Ltd 医薬組成物

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4845114A (en) * 1987-01-07 1989-07-04 Erregierre Industria Chimica Spa N-(trans-p-hydroxy-cyclohexyl)-(2-amino-3,5-dibromo)benzylamine salts possessing mucolytic activity

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105997902A (zh) * 2015-05-15 2016-10-12 苗怡文 一种治疗呼吸系统疾病的药物盐酸氨溴索组合物
CN106176629A (zh) * 2015-05-15 2016-12-07 苗怡文 一种制备治疗呼吸系统疾病的盐酸氨溴索冻干粉针剂的方法
CN106220518A (zh) * 2015-05-15 2016-12-14 苗怡文 一种制备治疗呼吸系统疾病的盐酸氨溴索化合物晶体的方法
CN106220517A (zh) * 2015-05-15 2016-12-14 苗怡文 一种制备用于制备盐酸氨溴索组合物的盐酸氨溴索化合物晶体的方法
CN106242983A (zh) * 2015-05-15 2016-12-21 苗怡文 一种制备治疗呼吸系统疾病的盐酸氨溴索化合物晶体的方法
CN106242982A (zh) * 2015-05-15 2016-12-21 苗怡文 一种制备治疗呼吸系统疾病的盐酸氨溴索化合物晶体的方法
CN106349088A (zh) * 2015-05-15 2017-01-25 苗怡文 一种制备治疗呼吸系统疾病的盐酸氨溴索化合物晶体的方法
CN104922079A (zh) * 2015-05-26 2015-09-23 苗怡文 一种祛痰的药物盐酸氨溴索冻干粉针剂组合物
CN104971057A (zh) * 2015-08-05 2015-10-14 青岛蓝盛洋医药生物科技有限责任公司 一种治疗呼吸系统疾病的药物盐酸氨溴索组合物胶囊
CN105012245A (zh) * 2015-08-10 2015-11-04 青岛蓝盛洋医药生物科技有限责任公司 一种化痰药物盐酸氨溴索组合物颗粒剂及其制备方法
CN105055321A (zh) * 2015-09-01 2015-11-18 青岛蓝盛洋医药生物科技有限责任公司 一种治疗咳嗽的药物盐酸氨溴索组合物干混悬剂

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CN1699337A (zh) 2005-11-23

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