WO2012134351A1 - COMPLEXES DE CLATHRATES DE β-CYCLODEXTRINE ET DES DÉRIVÉS DE 5-HYDROXY-4-AMINOMÉTHYL-1-CYCLOHEXYL (OU CYCLOHEPTYL)-3-ALCOXYCARBONYLE INDOLE POSSÉDANT UN EFFET ANTIVIRAL ET PROCÉDÉ DE LEUR PRODUCTION - Google Patents

COMPLEXES DE CLATHRATES DE β-CYCLODEXTRINE ET DES DÉRIVÉS DE 5-HYDROXY-4-AMINOMÉTHYL-1-CYCLOHEXYL (OU CYCLOHEPTYL)-3-ALCOXYCARBONYLE INDOLE POSSÉDANT UN EFFET ANTIVIRAL ET PROCÉDÉ DE LEUR PRODUCTION Download PDF

Info

Publication number
WO2012134351A1
WO2012134351A1 PCT/RU2012/000222 RU2012000222W WO2012134351A1 WO 2012134351 A1 WO2012134351 A1 WO 2012134351A1 RU 2012000222 W RU2012000222 W RU 2012000222W WO 2012134351 A1 WO2012134351 A1 WO 2012134351A1
Authority
WO
WIPO (PCT)
Prior art keywords
cyclohexyl
hydroxy
aminomethyl
cycloheptyl
derivative
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.)
Ceased
Application number
PCT/RU2012/000222
Other languages
English (en)
Russian (ru)
Inventor
Анатолий Федорович ЦЫБ
Анна Яковлевна ГОНЧАРОВА
Рахимджан Ахметджанович РОЗИЕВ
Илья Владимирович ВОРОБЬЕВ
Владимир Константинович ПОДГОРОДНИЧЕНКО
Владимирович ХОМИЧЁНОКВиктор
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.)
Obschestvo S Ogranichennoy Otvetstvennostyu <<nauchno-Issledovatelskaya Kompaniya <<medbiopharm>>
Original Assignee
Obschestvo S Ogranichennoy Otvetstvennostyu <<nauchno-Issledovatelskaya Kompaniya <<medbiopharm>>
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 Obschestvo S Ogranichennoy Otvetstvennostyu <<nauchno-Issledovatelskaya Kompaniya <<medbiopharm>> filed Critical Obschestvo S Ogranichennoy Otvetstvennostyu <<nauchno-Issledovatelskaya Kompaniya <<medbiopharm>>
Priority to EA201370198A priority Critical patent/EA024643B1/ru
Publication of WO2012134351A1 publication Critical patent/WO2012134351A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
    • C08B37/0012—Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
    • C08B37/0015—Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes
    • 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
    • A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
    • 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
    • A61P31/12—Antivirals
    • 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
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Definitions

  • Clathrate complexes of beta-cyclodextrin with a derivative of 5-hydroxy-4-aminomethyl-1-cyclohexyl (or cycloheptyl) -3-alkoxycarbonylindole having antiviral effects and methods for their preparation
  • the invention relates to new clathrate complexes (inclusion compounds) of ⁇ -cyclodextrin with a derivative of 5-hydroxy-4-aminomethyl-1-cyclohexyl (or cycloheptyl) -3-alkoxycarbonylindole having an antiviral effect, and methods for their preparation.
  • Clathrate complexes may find application in the pharmaceutical industry.
  • the invention also relates to compositions and drugs based on new clathrate cyclodextrin complexes.
  • New forms and ways of transporting drugs can expand the therapeutic potential of the prescribed treatment. Technologies for the transportation of drugs based on
  • SUBSTITUTE SHEET (RULE 26) complexes can significantly alter existing drugs, improving their bioavailability, reducing the therapeutic dose.
  • a water-soluble drug composition and a method for its preparation are described for such well-known drugs as Sibazon, Azaleptin, Mezapam, Indomethacin.
  • Pharmacological tests of the obtained complexes in laboratory animals showed a several-fold decrease in the therapeutic dose of drugs.
  • Molecules of cyclodextrins have a toroidal shape, and its internal cavity is hydrophobic. Water-soluble intermolecular complexes of lipophilic organic compounds are formed in solution due to the intercalation of their molecules in this cavity.
  • Complexes of ⁇ -cyclodextrin with non-steroidal anti-inflammatory drugs paracetamol, ibuprofen, ketoprofen, flufenamic and mefenamic acids, etc.
  • steroids paracetamol, ibuprofen, ketoprofen, flufenamic and mefenamic acids, etc.
  • prostaglandins and prostacyclins barbiturates
  • sulfonamides cardiac glycosides, and other drugs, for example, are available for treatment with antibiotics, etc.
  • US 4727064, RF patent 2337710 published in 2008, J.
  • the objective of this study is to find new clathrate complexes of ⁇ -cyclodextrin with an antiviral compound, which is a derivative of 5-hydroxy-4-aminomethyl-1-cyclohexyl (or cycloheptyl) -3-alkoxycarbonylindole, which have increased solubility in water, improved bioavailability.
  • the proposed clathrate complexes can reduce the dosage of the drug, and, therefore, reduce the toxicity of the drug.
  • the present invention is also the development of new methods for producing clathrate complexes and their use in pharmaceutical compositions and drugs.
  • the present invention relates to new clathrate complexes of ⁇ -cyclodextrin with a derivative of 5-hydroxy-4-aminomethyl-1-cyclohexyl (or cycloheptyl) -3-alkoxycarbo-yindole corresponding to the general formula (I) in a molar ratio of 5-hydroxy-4- derivative aminomethyl-1-cyclohexyl (or cycloheptyl) -3-alkoxycarbo-ylindole: ⁇ -cycle about dextrin from 1: 1 to 1: 5.
  • R 3 is C 3 alkyl
  • ALK- means Q-C b alkyl group
  • RR 2 are independently selected from C! -C4 -alkyl, preferably methyl, or Ri and R 2 together with a nitrogen atom (i.e., the group —NRiR 2 ) means groups corresponding to the formulas
  • Pharmaceutically acceptable salts include, first of all, hydrohalides, for example, hydrochlorides, mesylates, oxalates, tosylates, malonates, phosphates, etc.
  • a preferred clathrate complex is the 5-hydroxy-4-dimethylamino-2-methyl-1- ⁇ -cyclodextrin complex with ethyl ester cyclohexyl-III-indole-3-carboxylic acid (formula (II) and its hydrochloride (compound A).
  • the molar ratios of derivatives of 5-hydroxy-4-aminomethyl-1-cyclohexyl (or cycloheptyl) -3-alkoxycarbonylindole: the ⁇ -cycle of dextrin vary in the range from 1: 1 to 1: 5, allowing the complete translation compound in the clathrate complex, which significantly affects its bioavailability.
  • the clathrate complex like the nanocomplex proposed according to the present invention, has an antiviral effect and can be used to obtain most of the dosage forms and routes of administration used in medicine.
  • the invention also relates to a pharmaceutical composition having an antiviral effect, including in an effective amount the above clathrate complex of ⁇ -cyclodextrin with 5-hydroxy-4-aminomethyl-1-cyclohexyl (or cycloheptyl) -3-alkoxycarbonylindole derivatives of the general formula (I) (possibly in as nanoparticles) at a molar ratio of the above and pharmaceutically acceptable excipients.
  • the invention also relates to a medicament in the form of capsules or tablets in a pharmaceutically acceptable package containing the ⁇ -cycle o-dextrin clathrate complex with the derivative 5-hydroxy-4-aminomethyl-1-cyclohexyl (or cycloheptyl) -3-alkoxycarbonylindole of the general formula (I) in the molar ratio of the above, or a pharmaceutical composition based on it in an effective amount.
  • the clathrate complex can be used in the pharmaceutical composition or in the drug in the form of nanoparticles with a size of less than 100 nm
  • the pharmaceutical composition may contain adjuvants, such as fillers, moisturizers, emulsifiers, suspending agents, thickeners, sweeteners, perfumes, flavors.
  • adjuvants such as fillers, moisturizers, emulsifiers, suspending agents, thickeners, sweeteners, perfumes, flavors.
  • Pharmaceutically acceptable additives may be selected, for example, from microcellulose, lactose, calcium stearate, starch. The choice and ratio of these components depends on the nature and method of administration and dosage.
  • the content of the active ingredient is usually from 1 to 20 wt.%, In combination with one or more pharmaceutically acceptable additives, such as diluents, binders, disintegrating agents, adsorbents, flavoring agents, flavoring agents.
  • pharmaceutically acceptable additives such as diluents, binders, disintegrating agents, adsorbents, flavoring agents, flavoring agents.
  • the specified pharmaceutical composition and drug can be obtained by methods known in the pharmaceutical industry.
  • the active ingredient (compound of formula (I)) is mixed with a pharmaceutically acceptable carrier and, if necessary, with appropriate additives.
  • the drug may be in liquid or solid form.
  • solid dosage forms are, for example, tablets, pills, gelatin capsules, etc.
  • liquid dosage forms for injection and parenteral administration are solutions, emulsions, suspensions, etc.
  • the preparation of these dosage forms is carried out by methods traditional for the pharmaceutical industry — by mixing the components, tabletting, encapsulation etc.
  • the clathrate complexes proposed according to the present invention can be obtained in two ways:
  • the liquid-phase method consists in preparing an aqueous solution of the starting ⁇ -cyclodextrin and the alcohol corresponding derivative of 5-hydroxy-4-aminomethyl-1-cyclohexyl (or cycloheptyl) -3-alkoxycarbonylindole, which are then mixed with stirring and heating to a temperature not exceeding 75 ° C, in a molar ratio, the derivative of 5-hydroxy-4-aminomethyl-1-cyclohexyl (or cycloheptyl) -3-alkoxycarbononylindole or its pharmaceutically acceptable salt: ⁇ -cyclodextrin from 1: 1 to 1: 5, followed by stirring at indicated temperature until a homogeneous solution is obtained and the crystalline clathrate complex obtained is isolated.
  • Non-covalent clathrate complexes stabilized by hydrogen bonds are obtained.
  • Non-covalent complex is a complex that is formed between the molecules of substances in a suitable solvent due to intermolecular van der Waals interactions of a non-covalent nature, namely, hydrogen bonding.
  • the solid-phase method consists in the fact that ⁇ -cyclodextrin and a crystalline derivative of 5-hydroxy-4-aminomethyl-1-cyclohexyl (or cycloheptyl) -3-alkoxycarboninilindole or a pharmaceutically acceptable salt thereof at a temperature of 30-60 ° C are subjected to grinding at a speed of 400 rpm to 800 rpm for a period of time from 10 to 60 minutes, usually in a planetary ball mill, in modes from Shock-Shear to Shock, with a molar ratio of 5-hydroxy-4-aminomethyl-1-cyclohexyl derivative ( or cycloheptyl) -3-alkoxycarbonylindole or its pharmaceutically acceptable salt: ⁇ -cycle o dextrin from 1: 1 to 1: 5 (for compound A, the ratios 1: 1 and 1: 2 are optimal), with the isolation of the obtained crystalline clathrate complex, when necessary, in the form of nanoparticles with a particle
  • plastic deformation of a solid usually leads not only to a change in the shape of the solid, but also to the accumulation of defects in it that alter the physicochemical properties, including reactivity.
  • the accumulation of defects can be used in chemistry to accelerate reactions involving solids, reduce the temperature of processes, and other ways of intensifying chemical reactions in the solid phase.
  • a feature of the process of activation of a solid substance as a result of machining is that activation occurs when the particle size reaches a certain critical value as it is milled. During mechanical activation, the surface does not so much increase as defects accumulate in the entire crystal volume. This dramatically changes many of the physicochemical properties of solids, including reactivity.
  • the increase in reactivity as a result of mechanical activation can be considered as one of the methods for producing solids in a metastable, active form. Since chemical reactions involving solids, depending on the features of their mechanism, are sensitive to different defects that are contained in the crystal, the task of mechanical activation consists not only in the accumulation of defects in general, but also in obtaining the exact form defects, which is necessary for this reaction. This goal can be achieved both by selecting the conditions of mechanical action on the crystal (exposure energy, duration, relationship between pressure and shear, processing temperature, composition of the surrounding atmosphere), and taking into account the structural features of the crystal, the nature of the chemical bond, its strength characteristics, etc. .
  • a solid dispersion is usually first prepared, followed by optionally grinding or grinding the solid dispersion to an appropriate particle size.
  • Fine grinding of particles can be carried out mechanically by applying a force to the particles, under the influence of which they are crushed. Such a force can be provided in the collision of particles, which are given a high speed, with each other.
  • Fine grinding in order to obtain fine particles can be carried out, for example, by grinding, using an air-jet micron colloid mill, using a ball mill or using a pin mill.
  • the size of the resulting nanoparticles can be determined by any means well known in the industry.
  • the following methods can be used, for example: screening through sieves, sedimentation, electrozonal sensing (using a Coulter counter), microscopy, low-angle laser light scattering LALLS (abbreviation for Low-Angle Laser Light-Scattering - small-angle laser light scattering).
  • LALLS abbreviation for Low-Angle Laser Light-Scattering - small-angle laser light scattering
  • Preferred for use in the present invention are the particle size measurement methods most commonly used in the pharmaceutical industry, such as laser diffraction or sieve analysis.
  • the clathrate complex obtained according to the present invention in comparison with the previously known similar in structure and used in industry antiviral compound - arbidol, has not only increased solubility and Bioavailability, but also increased activity, which is unexpected and not obvious for this latrate complex.
  • Liquid phase method The calculated sample of ⁇ -cyclodextrin was dissolved in 0.5 l of distilled water at a temperature of 65-70 ° C. A portion of compound A was dissolved in 0.25 L of ethanol at the same temperature as the dextrin cycle. While stirring and heating, a solution of 1-cyclohexyl-4-aminomethyl-5-hydroxy-2-methyl-1 H-indole-3-carboxylic acid ethyl ester hydrochloride is added to the cyclodextrin solution. After mixing, the temperature was maintained at 65-70 ° C until a true solution was obtained, after which the temperature was lowered to 55 ° C for 2 hours. The alcohol from the solution was evaporated, and the aqueous residue was sent for freeze drying.
  • Solid-phase method The tests were carried out on a ball planetary mill Activator 2s with the material of grinding cups of aluminum oxide. The optimal regime was 400 rpm 5 min, 600 rpm 10 min, 400 rpm 5 min, 10 mm balls (zirconium oxide) to obtain the compound A: ⁇ -cyclodextrin complex. The molar ratios of the components also ranged from 1: 1 to 1: 3.
  • the resulting complex had a particle size of less than 100 nm.
  • a clathrate complex (1: 1) in the form of nanoparticles with the indicated size is confirmed by the analysis performed on a Zetasizer Nano ZS device ( Figure 1).
  • the measurement conditions are as follows: dispersion in water. Density 1,330, viscosity 0,8886sR, temperature 25 ° ⁇ , the attrition rate of 210, the average diameter of the particles obtained in this case is 32.6 nm.
  • the molar ratio of Compound A: ⁇ -cyclodextrin 1: 2 is optimal.
  • Possible additives microcellulose, lactose, calcium steorate, starch. Obtained by mixing the components in a Bectochem mixer and pressing on a Rimec tablet machine.
  • microcellulose lactose, starch.
  • mice were infected with the whole allantoic virus and its successive 10-fold dilutions. Data on the observation of animals for 15 days are presented in table 1. Studies on the antiviral activity of the antivirus in vivo were carried out at the Center for Chemistry of Medicinal Products (TsHLS-VNIHFI). The research results are shown in tables 1 and 2.
  • the data shown in table 2 indicate that the preparation of ethyl ester of 1-cyclohexyl-4-aminomethyl-5-hydroxy-2-methyl-1H-indole-3-carboxylic acid in the form of a clathrate complex with ⁇ -cyclodextrin in a ratio of 1 : 2, applied at doses of 30 and 60 mg / kg / day in antiviral activity superior to native ethyl ester of 1-cyclohexyl-4-aminomethyl-5-hydroxy-2-methyl-1 N-indole-3 - carboxylic acid, as evidenced by mortality protection rates of 50-70 and 30-40%, respectively.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Virology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Molecular Biology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nanotechnology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Materials Engineering (AREA)
  • Biochemistry (AREA)
  • Polymers & Plastics (AREA)
  • Pulmonology (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • Medical Informatics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)

Abstract

L'invention concerne de nouveaux complexes de clathrates de β-cyclodextrine et des dérivés de 5-hydroxy-4-aminométhyl-1-cyclohexyl (ou cycloheptyl)-3-alcoxycarbonyle indole qui se présentent comme des nanoparticules d'une taille inférieure à 100 nm, avec un rapport molaire de 1:1 à 1:5, possédant un effet antiviral et étant hautement actifs contre les virus de la grippe. Les complexes de clathrates sont obtenus par des procédés en phase solide ou en phase liquide. L'invention concerne aussi une composition pharmaceutique et un médicament basé sur ces complexes de clathrates.
PCT/RU2012/000222 2011-03-31 2012-03-27 COMPLEXES DE CLATHRATES DE β-CYCLODEXTRINE ET DES DÉRIVÉS DE 5-HYDROXY-4-AMINOMÉTHYL-1-CYCLOHEXYL (OU CYCLOHEPTYL)-3-ALCOXYCARBONYLE INDOLE POSSÉDANT UN EFFET ANTIVIRAL ET PROCÉDÉ DE LEUR PRODUCTION Ceased WO2012134351A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EA201370198A EA024643B1 (ru) 2011-03-31 2012-03-27 КЛАТРАТНЫЕ КОМПЛЕКСЫ β-ЦИКЛОДЕКСТРИНА С ПРОИЗВОДНЫМ 5-ГИДРОКСИ-4-АМИНОМЕТИЛ-1-ЦИКЛОГЕКСИЛ( ИЛИ ЦИКЛОГЕПТИЛ)-3-АЛКОКСИКАРБОНИЛИНДОЛА, ОБЛАДАЮЩИЕ ПРОТИВОВИРУСНЫМ ДЕЙСТВИЕМ, И СПОСОБЫ ИХ ПОЛУЧЕНИЯ

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
RU2011112073/04A RU2464042C1 (ru) 2011-03-31 2011-03-31 КЛАТРАТНЫЙ КОМПЛЕКС β-ЦИКЛОДЕКСТРИНА С ПРОИЗВОДНЫМ 5-ГИДРОКСИ-4-АМИНОМЕТИЛ-1-ЦИКЛОГЕКСИЛ(ИЛИ ЦИКЛОГЕПТИЛ)-3-АЛКОКСИКАРБОНИЛИНДОЛА, СПОСОБ ЕГО ПОЛУЧЕНИЯ (ВАРИАНТЫ), ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И ЛЕКАРСТВЕННОЕ СРЕДСТВО
RU2011112073 2011-03-31

Publications (1)

Publication Number Publication Date
WO2012134351A1 true WO2012134351A1 (fr) 2012-10-04

Family

ID=46931722

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/RU2012/000222 Ceased WO2012134351A1 (fr) 2011-03-31 2012-03-27 COMPLEXES DE CLATHRATES DE β-CYCLODEXTRINE ET DES DÉRIVÉS DE 5-HYDROXY-4-AMINOMÉTHYL-1-CYCLOHEXYL (OU CYCLOHEPTYL)-3-ALCOXYCARBONYLE INDOLE POSSÉDANT UN EFFET ANTIVIRAL ET PROCÉDÉ DE LEUR PRODUCTION

Country Status (3)

Country Link
EA (1) EA024643B1 (fr)
RU (1) RU2464042C1 (fr)
WO (1) WO2012134351A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2570382C1 (ru) * 2014-12-10 2015-12-10 Общество с ограниченной ответственностью "ЛАЙФ САЙНСЕС ОХФК" Фармацевтическая композиция и лекарственное средство на основе клатратного комплекса 7-бром-5-(орто-хлорфенил)-2,3-дигидро-1н-1,4-бензодиазепин-2-она с циклодекстрином, способы его получения (варианты)
RU2761429C2 (ru) * 2018-06-13 2021-12-08 Общество с ограниченной ответственностью "Тиацен" Средство, обладающее противоопухолевым действием, для лечения онкологических заболеваний

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4727064A (en) * 1984-04-25 1988-02-23 The United States Of America As Represented By The Department Of Health And Human Services Pharmaceutical preparations containing cyclodextrin derivatives
US4956351A (en) * 1987-07-01 1990-09-11 Janssen Pharmaceutica N.V. Frame-543 Antiviral pharmaceutical compositions containing cyclodextrins
RU2099354C1 (ru) * 1990-01-23 1997-12-20 Дзе Юниверсити оф Канзас Очищенное производное циклодекстрина, клатратный комплекс очищенного производного циклодекстрина с лекарственным средством, фармацевтическая композиция
RU2128664C1 (ru) * 1996-08-14 1999-04-10 Закрытое акционерное общество "Производственно-коммерческая Ассоциация АЗТ" СОЕДИНЕНИЕ ВКЛЮЧЕНИЯ 9-(2-ОКСИЭТОКСИМЕТИЛ)ГУАНИНА С β-ЦИКЛОДЕКСТРИНОМ, ОБЛАДАЮЩЕЕ АНТИГЕРПЕСНОЙ АКТИВНОСТЬЮ
RU2386616C2 (ru) * 2008-04-23 2010-04-20 Общество С Ограниченной Ответственностью "Бинатех" Производные 5-гидрокси-4-аминометил-1-циклогексил (или циклогептил)-3-алкоксикарбонилиндолов, их фармацевтически приемлемые соли, обладающие противовирусной активностью, и способ их получения
US20100204179A1 (en) * 2007-07-23 2010-08-12 Andre Arigony Souto Resveratrol complex and process for the preperation

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5221669A (en) * 1991-04-19 1993-06-22 The United States Of America As Represented By The Department Of Health And Human Services Antiviral compositions containing α-cyclodextrin sulfates alone and in combination with other known antiviral agents and glucocorticoids and methods of treating viral infections
DE19814815C2 (de) * 1998-04-02 2000-10-12 Gerhard Steffan Sterinverknüpfte, anionische Cyclodextrinderivate und deren Verwendung in Arzneimittelformulierungen
US20050209189A1 (en) * 2001-03-06 2005-09-22 Roger Hershline Antiviral composition
US7622581B2 (en) * 2004-05-17 2009-11-24 Tibotec Pharmaceuticals Ltd. 6,7,8,9-substituted 1-phenyl-1,5-dihydro-pyrido[3,2-b]indol-2-ones useful as anti-infective pharmaceutical agents
CA2600510C (fr) * 2005-03-11 2010-11-02 Pfizer Inc. Formes cristallines d'un derive d'imidazole
BRPI0616447A2 (pt) * 2005-09-30 2011-06-21 Ovation Pharmaceuticals Inc complexo de inclusão de carbamazepina-ciclodextrina, método de administrar e método de preparar o mesmo

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4727064A (en) * 1984-04-25 1988-02-23 The United States Of America As Represented By The Department Of Health And Human Services Pharmaceutical preparations containing cyclodextrin derivatives
US4956351A (en) * 1987-07-01 1990-09-11 Janssen Pharmaceutica N.V. Frame-543 Antiviral pharmaceutical compositions containing cyclodextrins
RU2099354C1 (ru) * 1990-01-23 1997-12-20 Дзе Юниверсити оф Канзас Очищенное производное циклодекстрина, клатратный комплекс очищенного производного циклодекстрина с лекарственным средством, фармацевтическая композиция
RU2128664C1 (ru) * 1996-08-14 1999-04-10 Закрытое акционерное общество "Производственно-коммерческая Ассоциация АЗТ" СОЕДИНЕНИЕ ВКЛЮЧЕНИЯ 9-(2-ОКСИЭТОКСИМЕТИЛ)ГУАНИНА С β-ЦИКЛОДЕКСТРИНОМ, ОБЛАДАЮЩЕЕ АНТИГЕРПЕСНОЙ АКТИВНОСТЬЮ
US20100204179A1 (en) * 2007-07-23 2010-08-12 Andre Arigony Souto Resveratrol complex and process for the preperation
RU2386616C2 (ru) * 2008-04-23 2010-04-20 Общество С Ограниченной Ответственностью "Бинатех" Производные 5-гидрокси-4-аминометил-1-циклогексил (или циклогептил)-3-алкоксикарбонилиндолов, их фармацевтически приемлемые соли, обладающие противовирусной активностью, и способ их получения

Also Published As

Publication number Publication date
EA201370198A1 (ru) 2014-01-30
RU2464042C1 (ru) 2012-10-20
EA024643B1 (ru) 2016-10-31

Similar Documents

Publication Publication Date Title
RU2451680C1 (ru) Клатратный комплекс циклодекстрина или арабиногалактана с 9-фенил-симм-октагидроселеноксантеном, способ его получения (варианты), фармацевтическая композиция и лекарственное средство
Joshi et al. Nanocrystalization: an emerging technology to enhance the bioavailability of poorly soluble drugs
RU2448120C1 (ru) Клатратные комплексы бета-циклодекстрина с 1-{[6-бром-1-метил-5-метокси-2-фенилтиометил-1-н-индол-3-ил]карбонил}-4-бензилпиперазином, обладающие противовирусной активностью, их получение и применение
JP7196378B2 (ja) 高分子－シクロデキストリン－脂質共役体
WO2014161131A1 (fr) Préparation d&#39;un complexe d&#39;inclusion de méloxicam-β-cyclodextrine amorphe par l&#39;intermédiaire d&#39;un procédé de séchage par atomisation
Ndlovu et al. Domperidone nanocrystals with boosted oral bioavailability: fabrication, evaluation and molecular insight into the polymer-domperidone nanocrystal interaction
Borba et al. The effect of mechanical grinding on the formation, crystalline changes and dissolution behaviour of the inclusion complex of telmisartan and β-cyclodextrins
Timóteo et al. Layered double hydroxides of CaAl: A promising drug delivery system for increased dissolution rate and thermal stability of praziquantel
Mondal et al. Development and characterization of a phospholipid complex for effective delivery of capsaicin.
Al-Japairai et al. Lyophilized amorphous dispersion of telmisartan in a combined carrier–alkalizer system: Formulation development and in vivo study
CN113260359A (zh) 酒精解毒剂
RU2464042C1 (ru) КЛАТРАТНЫЙ КОМПЛЕКС β-ЦИКЛОДЕКСТРИНА С ПРОИЗВОДНЫМ 5-ГИДРОКСИ-4-АМИНОМЕТИЛ-1-ЦИКЛОГЕКСИЛ(ИЛИ ЦИКЛОГЕПТИЛ)-3-АЛКОКСИКАРБОНИЛИНДОЛА, СПОСОБ ЕГО ПОЛУЧЕНИЯ (ВАРИАНТЫ), ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И ЛЕКАРСТВЕННОЕ СРЕДСТВО
Naeem et al. Salt and non-salt forming excipients to improve the dissolution of dexibuprofen; formulation of chewable tablets
Sherje et al. Inclusion complexes of hydroxy propyl-β-cyclodextrin and paliperidone: preparation and characterization
HUP1000327A2 (en) Composition containing nanostructured ezetibime and process for it&#39;s preparation
CN1298314C (zh) 含有碱性氨基酸ⅱ的o－乙酰水杨酸的稳定盐
Zidan et al. Enhancement of glimepiride bioavailability by co-crystallization technique
Ain et al. Cyclodextrins: versatile carrier in drug formulations and delivery systems
US20090012284A1 (en) Process for the Preparation of a Piroxicam: Betacyclodextrin Inclusion Compound
WO2011154755A1 (fr) Atorvastatine nanostructurée, ses sels pharmaceutiquement acceptables et des compositions de ceux-ci, procédé pour leur préparation et compositions pharmaceutiques les contenant
Pilli et al. ETODOLAC DISSOLUTION IMPROVEMENT BY PREPARATION OF SOLID DISPERSIONS WITH CYCLODEXTRIN COMPLEX'S
Aher et al. Formulation and Evaluation of ketoprofen nanosuspension
RU2570382C1 (ru) Фармацевтическая композиция и лекарственное средство на основе клатратного комплекса 7-бром-5-(орто-хлорфенил)-2,3-дигидро-1н-1,4-бензодиазепин-2-она с циклодекстрином, способы его получения (варианты)
Nagasamy Venkatesh et al. Dissolution enhancement of diacerein using water soluble carrier by solid dispersion technology
RU2640081C1 (ru) Фармацевтическая композиция и лекарственное средство на основе клатратного комплекса N-карбамоилметил-4-фенил-2-пирролидон или 4-фенилпирацетам с циклодекстрином, способы его получения (варианты)

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: 12764162

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 201370198

Country of ref document: EA

122 Ep: pct application non-entry in european phase

Ref document number: 12764162

Country of ref document: EP

Kind code of ref document: A1