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WO2015108440A1 - Composition pharmaceutique sous forme de comprimé et procédé de fabrication correspondant - Google Patents

Composition pharmaceutique sous forme de comprimé et procédé de fabrication correspondant Download PDF

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Publication number
WO2015108440A1
WO2015108440A1 PCT/RU2014/000164 RU2014000164W WO2015108440A1 WO 2015108440 A1 WO2015108440 A1 WO 2015108440A1 RU 2014000164 W RU2014000164 W RU 2014000164W WO 2015108440 A1 WO2015108440 A1 WO 2015108440A1
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WO
WIPO (PCT)
Prior art keywords
glutaryl histamine
composition
pharmaceutical composition
sieved
lactose monohydrate
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/RU2014/000164
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English (en)
Russian (ru)
Inventor
Владимир Евгеньевич НЕБОЛЬСИН
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.)
Valenta Intellect LLC
Original Assignee
Valenta Intellect LLC
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 Valenta Intellect LLC filed Critical Valenta Intellect LLC
Priority to HK16102807.1A priority Critical patent/HK1214767B/xx
Priority to SG11201505385VA priority patent/SG11201505385VA/en
Priority to CN201480006100.3A priority patent/CN105307650B/zh
Publication of WO2015108440A1 publication Critical patent/WO2015108440A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders

Definitions

  • the invention relates to medicine, the pharmaceutical industry and relates to agents having nootropic and neuromodulatory activity.
  • the glutaryl histamine of the formula is mixed with various excipients to obtain a solid form of glutaryl histamine.
  • the solid form is a tablet form; in other embodiments, it is a capsule.
  • An additional aspect of the present invention includes a method for preparing glutaryl histamine formulations.
  • Other aspects of the present invention include the use of these compositions for the treatment of a viral disease in a mammal in need thereof, which comprises administering to the mammal a therapeutically effective amount of the compositions of the present invention.
  • Influenza is one of the most dangerous, in an epidemic respect, infection. For example, annually, in the Russian Federation, about 7 million cases of influenza infection are recorded, per 142 million people. Which is about 20% in the structure of infectious and parasitic diseases and this is a significant indicator.
  • One of the evolutionary features of the influenza virus is its high ability for rapid mutations due to antigenic variation. Influenza viruses are common in both humans and some animal species, including mammals and birds. So the influenza viruses of some animals, for example, birds and pigs, are the most pathogenic.
  • Vaccine therapy has good indicators of preventing morbidity and / or a decrease in the intensity of the disease. And even such events cannot stop the massive outbreaks of the disease, especially in the cold season.
  • One of the adverse events is the fulminant form, the so-called, rapid development of hemorrhagic toxic pulmonary edema and death from respiratory and cardiovascular failure [Int. J. Tuberc. Lung dis. // 2007- V.11. - N7. - S.710-721].
  • amantadine and remantadine which are antiviral against influenza virus strains, have been widely used and are still being used.
  • the antiviral drug Remantadine has spread. It is used to treat and prevent infection caused by type A influenza viruses. A pronounced therapeutic effect, the drug showed against the influenza virus subtype H3N2.
  • the mechanism of action on the virus is associated with the blocking of the function of the viral protein inside the membrane. Inhibition of viral activity occurs at the stages of receptor-mediated endocytosis, decapsidation in the phagolysosome, as well as the assembly and budding of viral particles [Vestnik RAMS // 1993. - N 3. - P.10-15].
  • remantadine as a representative of the adamantane group, has limitations in its use. At high doses, side effects from the central nervous system occur, in particular, it can cause convulsive effects. It also has an adverse effect on the liver and kidneys, which makes it unlikely to be used in people with diseases of these organs.
  • influenza A and B virus neuraminidase inhibitors are widely used - oseltamivir phosphate (oseitamivir) and zanamivir (zanamivir), which, when combined with the hydrophobic portion of the active portion of the influenza virus neuraminidase, blocks the ability of the latter to cleave sialic acid residues from the surface of the infected cell, thereby most suppressing the exit from it of newly formed virions.
  • Oseltamivir is the trade name of Tamiflu ®
  • zanamivir is the trade name of Relenza ®
  • Currently, there are cases of resistance to oseltamivir and zanamivir [Menno D. de Jong, Tran Tan Thanh, Truong Huu Khanh et al. Oseitamivir Resistance during Treatment of Influenza A (H5N1) Infection // N. Engi.
  • Highly pathogenic viral diseases also include severe acute respiratory syndrome (SARS), a new acute coronavirus disease caused by a causative agent of genotype IV and characterized by a mortality rate of up to 10% [Revised U.S. Surveillance case definition for severe acute respiratory syndrome (SARS) and update on SARS cases - United States and worldwide, December 2003 // MMWR Wkly Rep. - 2003. - Vol. 52, N. 49. - P. 1202-1206].
  • SARS severe acute respiratory syndrome
  • SARS severe acute respiratory syndrome
  • the present invention provides the manufacture of a glutaryl histamine composition, not containing magnesium salts of silicic acids and / or talc.
  • Other embodiments include glutaryl histamine compositions with one or more diluents, disintegrants, binders, and lubricants.
  • a composition is provided which consists of glutaryl histamine with one or more diluents, disintegrating agents, binders and lubricants.
  • the composition comprises glutaryl histamine, one or more diluents, wherein the diluent is selected from starch, lactose monohydrate or microcrystalline cellulose, one or more disintegrants, each independently selected from pregelatinized starch or cross-linked sodium carboxymethyl cellulose , binder and lubricant.
  • the binder is selected from polyvinylpyrrolidone
  • the lubricant is selected from the magnesium salt of silicic acid.
  • the diluent is selected from lactose monohydrate
  • the disintegrant is selected from the group consisting of croscarmellose sodium
  • the binder the substance is povidone.
  • Excipients are selected to deliver an appropriate amount of glutaryl histamine in an industrially manufactured dosage form. All excipients are selected and are inert, acceptable organoleptically and compatible with glutaryl histamine. Excipients that are used in solid oral formulations typically include fillers or diluents, binders, disintegrants, lubricants, release agents, glidants, moisturizers and surfactants, colorants, flavors, sweeteners, adsorbents and substances that improve organoleptic properties.
  • Excipients or diluents are added to the active substance in order to increase the volume of the tablet.
  • lactose which can be either crystalline or amorphous.
  • Various types of lactose include lactose monohydrate, alpha-lactose monohydrate, such as: anhydrous forms of lactose ( ⁇ -, ⁇ -) and agglomerated lactose.
  • Other diluents include sugars, such as derivatives of sugars.
  • One of the most used excipients is lactose monohydrate. Also use microcrystalline cellulose and in the form of microparticles.
  • starch and starch derivatives are referred to diluents and fillers.
  • starches include pregelatinized starch and sodium glycolate modified starch.
  • Starches and starch derivatives may also be disintegrants.
  • Other diluents include inorganic salts such as dibasic calcium phosphate, tribasic calcium phosphate and calcium sulfate.
  • Polyols such as mannitol, sorbitol and xylitol can also serve as diluents.
  • Many diluents also act as disintegrants and binders, and these additional properties must be taken into account when developing the formulation.
  • Disintegrants are included in tablet formulations for disintegrating tablets into particles of the active pharmaceutical component and excipients, which will facilitate the dissolution of the active component and increase the bioavailability of the active component.
  • the disintegrant is gelatinized starch.
  • Another disintegrant is cross-linked sodium carboxymethyl cellulose; also disintegrants include cross-linked polyvinylpyrrolidone (e.g. crospovidone), microcrystalline
  • Binders are used in wet granulation.
  • the binder performs the function of fluidity of the powder and for pressing.
  • the binders are cellulose derivatives such as microcrystalline cellulose, methyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose and hydroxypropyl cellulose.
  • binders are polyvidone, polyvinylpyrrolidone, gelatin, natural gums, for example acacia, tragacanth, guar and pectin resins, starch paste, pregelatinized starch, sucrose, corn syrup, polyethylene enenglycols and sodium magnesium alginate, magnesium ammonium alginate, calcium magnesium ammonium aluminate, calcium ammonium aluminate, magnesium ammonium aluminate, calcium magnesium, ammonium alginate, calcium magnesium, ammonium alginate, magnesium alginate, calcium magnesium, ammonium alginate, magnesium alginate.
  • a preferred, but not exclusive, binder is polyvinylpyrrolidone, in particular povidone.
  • Lubricants are used in tablet formulations to prevent sticking of the tablet to the impact surface and to reduce friction during the pressing stages.
  • Lubricants typically include vegetable oils, such as corn oil, mineral oils, PEG polyethylene glycols, stearic acid salts such as calcium stearate, magnesium stearate and sodium stearyl fumarate, mineral salts, for example talc, inorganic salts, for example sodium chloride, organic salts, for example sodium benzoate, sodium acetate and sodium oleate ) and polyvinyl alcohols.
  • the lubricant is magnesium stearate.
  • Glidants are used in solid dosage forms to improve tablet flow.
  • the implementation of glutaryl histamine is from about 30-50% by weight of the composition.
  • This composition in this embodiment contains a diluent, which is lactose monohydrate, also a diluent selected from microcrystalline cellulose, a disintegrant selected from pregelatinized starch, a second disintegrant selected from cross-linked carboxymethyl cellulose, a binder a substance selected from polyvinylpyrrolidone; and a lubricant that is selected from magnesium stearate.
  • lactose monohydrate is about 25-40%
  • microcrystalline cellulose is about 5-15%
  • pregelatinized starch is about 5-15%
  • cross-linked sodium carboxymethyl cellulose is about 1-10%
  • polyvinylpyrrolidone is about 1-10 %
  • magnesium stearate is about 0.2-2.0%.
  • glutaryl histamine is about 40.0% by weight of the composition
  • lactose monohydrate is about 30%
  • microcrystalline cellulose is about 10.5%
  • pregelatinized starch is about 1 1%
  • croscamellose is about 4.0%
  • povidone is about 5.5%
  • magnesium stearate is about 0.5%.
  • glutaryl histamine comprises up to 80% (70-80%) by weight of the composition.
  • the composition may additionally contain lactose in an amount of 2.5-20% by weight of the composition; a disintegrating substance, namely, cross-linked carboxymethyl cellulose, in an amount of from 1-10% by weight of the composition; the binder selected for example, polyvinylpyrrolidone, in an amount of from 2-10% of mass of the composition; and a lubricant selected from the group of stearates, for example, magnesium (potassium) stearate, in an amount of 0.2-2.0% by weight of the composition.
  • lactose in an amount of 2.5-20% by weight of the composition
  • a disintegrating substance namely, cross-linked carboxymethyl cellulose
  • the binder selected for example, polyvinylpyrrolidone, in an amount of from 2-10% of mass of the composition
  • a lubricant selected from the group of stearates, for example, magnesium (potassium) stearate, in an amount of 0.2-2.0% by weight of the composition.
  • lactose monohydrate is selected as a diluent
  • sodium croscarmellose is selected as a disintegrant
  • povidone is used as a binder
  • magnesium stearate is used as a lubricant.
  • the content of glutaryl histamine is up to 80% by weight of the composition
  • lactose monohydrate is selected as a diluent, the content of which is 8-15% by weight of the composition
  • a disintegrant is selected cross-linked sodium carboxymethyl cellulose in an amount of 1-10% by weight of the composition
  • the binder is polyvinylpyrrolidone, with a content of 1-10% by weight of the composition
  • a binding agent of magnesium stearate with a content of 0.2-2.0% by weight of the composition.
  • the diluent is selected from lactose monohydrate, with a content of 9.5% by weight of the composition
  • the disintegrant is selected from croscarmellose sodium, and is 5% by weight of the composition
  • the binder is povidone, with a content of 5% by weight of the composition
  • lubricating the substance is magnesium stearate, and in an amount of 0.5% by weight of the composition.
  • glutaryl histamine comprises about 90% by weight of the composition.
  • the composition also contains a diluent, for example lactose monohydrate, in preferred amounts of 3-10% by weight of the composition; a disintegrant, such as cross-linked carboxymethyl cellulose, in an amount of 2-5% by weight of the composition; a binder, such as polyvinylpyrrolidone, in an amount of 2-5% by weight of the composition; a lubricant, such as magnesium stearate, in an amount of 0.2-2.0% by weight of the composition.
  • a diluent for example lactose monohydrate
  • a disintegrant such as cross-linked carboxymethyl cellulose
  • a binder such as polyvinylpyrrolidone
  • a lubricant such as magnesium stearate
  • the diluent is selected from lactose monohydrate, in an amount of 3.5% by weight of the composition
  • the disintegrant is selected from croscarmellose sodium, and it makes up about 3% by weight of the composition
  • the binder is povidone, with a content of about 3% by weight composition
  • the lubricant is selected from magnesium stearate with a content of about 1% by weight of the composition.
  • the present invention provides that the composition is glutaryl histamine, in an amount of 90 mg, where glutaryl histamine is contained in an amount of 40-90% by weight of the composition.
  • glutaryl histamine in the composition contains in the amount of 60-90% or may be in the amount of 70-80%.
  • these compositions may contain one or more of the starches, for example, corn starch, pregelatinized starch, cross-linked sodium salt of carboxymethyl ether starch, lactose monohydrate, microcrystalline cellulose, cross-linked sodium carboxymethyl cellulose; hydroxypropyl methylcellulose; polyvinylpyrrolidone, a silicate salt, for example magnesium silicate; a stearic acid salt, for example potassium stearate; and a mineral compound such as talc.
  • starches for example, corn starch, pregelatinized starch, cross-linked sodium salt of carboxymethyl ether starch, lactose monohydrate, microcrystalline cellulose, cross-linked sodium carboxymethyl cellulose; hydroxypropyl methylcellulose; polyvinylpyrrolidone, a silicate salt, for example magnesium silicate; a stearic acid salt, for example potassium stearate; and a mineral compound such as talc.
  • these compositions preferably, but not exclusively, contain one unit dose of glutaryl histamine.
  • the unit dose is in the form of a solid dosage form, such as a tablet or capsule, and more preferably is a tablet.
  • the tablet may include 30, 60, 100 and preferably 90 mg of glutaryl histamine in a solid dosage form of 250 mg.
  • a method for preparing a solid dosage form of glutaryl histamine by wet mixing glutaryl histamine and auxiliary substances with water, granulation, drying and grinding the granular mixture.
  • the final mixture is compressed into a tablet. In other embodiments, the final mixture is encapsulated.
  • the process includes the steps of dry mixing glutaryl histamine and one or more excipients to form a dry mixture; wetting the dry mixture with pre-prepared water to obtain a wet granulation mixture; drying to obtain a dry granulation mixture; grinding to obtain a crushed granulation mixture; mixing with the lubricant crushed granulation mixture to obtain the finished mixture; obtaining from the finished mixture a solid dosage form for oral administration.
  • the final blended mixture is compressed into tablets.
  • the final mixed mixture is encapsulated.
  • Glutaryl histamine sifted 100% - 3,000 (7,751) kg, dry sifted potato starch - 1,414 (3,652) kg, lactose (milk sugar) sifted - 4, 193 (10,832) kg, 5% starch paste - 2,028 (5,240) kg weighed scales in production tanks.
  • a high-speed mixer-granulator for example, GHL-250 GF-335 (for the minimum series: in the production capacity of GF-201), sieved glutaryl histamine is charged, dry sifted potato starch, sifted lactose (milk sugar) and sifted for 3-5 minutes. Next, add 5% starch paste and mix for 20-3 Osek, (for a minimum series: 2-3 minutes) until a uniformly moistened mass is obtained. When squeezed in the hand, the mass crumbles easily and breaks up with a light blow.
  • the wetted mass is transferred to the drying operation.
  • the moistened mixture is dried in a granulator in a fluidized bed FL-60 ⁇ -337 at a temperature of (45 ⁇ 5) ° ⁇ , for 20-45 min until a residual moisture content of 2.0-3.0% (Sartorius moisture analyzer at 100 ° ⁇ ) or (for the minimum series: the moistened mixture is dried in air, on trays, 10-12 hours).
  • a sample of the dried mass, before determining the moisture content in it on a Sartorius moisture analyzer, must be granulated in order to obtain a more accurate result.
  • the dried mixture is discharged into production tanks and passed through a universal granulator GR-1 GF-332 with a diameter of drum openings of 1.0-1.5 mm (for the smallest series: through a manual sieve GF-210 with a diameter of openings of 1000 microns in a VSH-fume hood 208 (1)) and collected in production tanks (KT-3; TP-3.2).
  • the tablet mass is averaged in a DR-5 GF-340 pelletizing boiler for 3-5 minutes, the sample of the tablet mass is analyzed for glutaryl histamine content and upon receipt positive results, the tablet mass is transferred to the stage of tabletting. (CT-3, TP-4.1)
  • Tableting is carried out on a rotary pressing machine MRC-30N GF-230 with a diameter of punches of 9 mm
  • the tablets should be flat or white with a creamy tint, flat-cylindrical with bevel and notch, with solid edges, smooth and uniform surface, without cracks and chips.
  • a label is indicated on the MRC-30N GF-230 rotary pressing machine indicating the name of the preparation, batch number, and tablet weight.
  • a tablet mass is loaded into the press hopper and tabletting is started. Filling the tablet mass and dedusting the tablets is automatic. During tabletting, check the average weight of the tablets, the deviation from the average weight of the tablets, description, strength.
  • Discard substandard tablets collect in containers GF-201 and send them to grind into a granulator universal GR-1 GF-332. Air-conditioned tablets are held for 6-8 hours to relax the stress inside the tablet resulting from high pressure during compression.
  • the moistened mass is collected in production tanks GF-201, 302 and transferred to the drying operation TP-3.2.
  • the wet mixture is dried in a granulator dryer ⁇ - ⁇ exerc ⁇ -219 (1, 2), a granulator in a fluidized bed FL-60 GF-337 at a temperature of (55 ⁇ 5) ° ⁇ for 40-60 min until the residual moisture content 2.0-3.0%.
  • the dried mixture is discharged into production tanks GF-201, GF-302 and passed through a universal granulator GR-1 GF-218 (2), GF-332 (2) with a diameter of the drum holes 1, 0-1, 5 mm and collected in production containers GF-201, GF-302 (CT-3; TP-3.2). Dry granulate is passed to the stage of obtaining the mixture for encapsulation TP-4.1.
  • Encapsulation is carried out on the MG Compact GF-237 capsule filling line, NJP-800C GF-338 automatic capsule filling machine, SF-100N GF-automatic capsule filling machine.
  • the capsule mixture is loaded into hopper 1 of the capsule machine and loaded into hopper 2 hard gelatin capsules and begin encapsulation.
  • the encapsulation mixture is added automatically as the bins are empty.
  • the objective of the invention is the expansion of the arsenal of funds with virusotropic and immunogenic activity.
  • a new pharmaceutical composition in solid dosage form with virusotropic and immunogenic activity, characterized in that it includes glutaryl histamine in the mass up to 94 wt% and excipients up to 100% as an active principle.
  • the content of glutaryl histamine may be from 80 to 94% of the mass.
  • the dosage form may contain lactose monohydrate, cellulose microcrystalline, croscarmellose sodium, silicon colloidal dioxide (Aerosil 300) and calcium stearate.
  • Such a high content of active principle is not disclosed in the prior art.
  • a special case of a new pharmaceutical composition in the form of tablets with virusotropic and immunogenic activity is a dosage form, characterized in that it includes glutaryl histamine as an active principle, lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide (aerosil 300 ) and calcium stearate in the following ingredients, wt.%:
  • Glutaryl histamine 18.0-75 microcrystalline cellulose 18.0-71 croscarmellose sodium 0.25-1 silicon colloidal dioxide (Aerosil 300) 0.5-2 calcium stearate 0.5-2 lactose monohydrate else To further increase the stability of the composition, active substance pre-dried to a moisture content of not more than 1.5%. Examples of implementation:
  • Example L Composition.
  • Example B Composition.
  • lactose monohydrate BP / Eur.Ph. Or USP-NF
  • BP / Eur.Ph. Or USP-NF lactose monohydrate
  • the composition of glutaryl histamine can be attributed to relatively harmless drugs.
  • composition has no allergenic, mutagenic properties. 3.
  • composition of glutaryl histamine does not have reproductive toxicity.
  • composition in all studied doses (0.05, 0.5, 5.0 mg / kg glutaryl histamine) does not have carcinogenic activity, which was shown in a 24-month experiment.
  • mice weighing 15 g obtained from vivarium of the VTs NIIM MO RF.
  • the glutaryl histamine composition at a concentration of 100-200 ⁇ g / ml effectively inhibits the reproduction of influenza A virus (strain A / Aichi / 2/68 (H3N2) and A / chicken / Kurgan / Russia / 2/05 (H5N1)) when applied 2 hours after infection of the monolayer.
  • the 5 mg / kg glutaryl histamine composition is effective as a prophylactic against influenza A (H3N2 and H5N1).
  • the prophylactic efficacy of the glutaryl histamine composition is somewhat inferior to Tamiflu.
  • the composition of glutaryl histamine When used according to the emergency prevention and treatment regimen, the composition of glutaryl histamine is inferior to Tamiflu.
  • the optimal dose when using the glutaryl histamine composition according to this scheme is -15 mg / kg. 3.3. Study of the interferon-inducing and immunomodulating activity of the glutaryl histamine composition
  • glutaryl histamine composition oral administration.
  • a single oral administration in 73.3% of the donors causes an increase in the content of IFN in the blood within the upper limits of the physiological norm after 24-48 hours.
  • a single dose of the glutaryl histamine composition stimulates the production of gamma IFN.
  • the new composition showed high results of pharmacological activity and can be recommended for implementation in clinical practice.
  • the invention is applicable in the field of medicine, the pharmaceutical industry, in particular in the manufacture of agents having nootropic and neuromodulatory activity, and relates to new compositions of glutaryl histamine and methods for their production.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Chemical & Material Sciences (AREA)
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Abstract

L'invention concerne la médecine et plus particulièrement et l'industrie chimique et pharmaceutique et porte sur des médicaments possédant une activité tropique antivirale et immunogène. La composition pharmaceutique sous forme de comprimé possédant une activité tropique antivirale et immunogène est caractérisée en ce qu'elle comprend en tant que substance active de la glutaryle histamine et en tant que substances auxiliaires le monohydrate de lactose, la cellulose microcristalline, la croscarmellose sodium, le dioxyde de silicium colloïdal (Aerosil 300) et le stéarate de sodium.
PCT/RU2014/000164 2014-01-20 2014-03-14 Composition pharmaceutique sous forme de comprimé et procédé de fabrication correspondant Ceased WO2015108440A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
HK16102807.1A HK1214767B (en) 2014-01-20 2014-03-14 Tablet-formed pharmaceutical composition and preparation method thereof
SG11201505385VA SG11201505385VA (en) 2014-01-20 2014-03-14 Pharmaceutical composition in the form of a tabletand a method for producing same
CN201480006100.3A CN105307650B (zh) 2014-01-20 2014-03-14 片剂形式的药物组合物及其制造方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
RU2014101563 2014-01-20
RU2014101563/15A RU2546002C1 (ru) 2014-01-20 2014-01-20 Фармацевтическая композиция в форме таблетки и способ ее получения

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WO2015108440A1 true WO2015108440A1 (fr) 2015-07-23

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Cited By (2)

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RU2546002C1 (ru) 2015-04-10
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