WO2007105981A1 - Solid oral form of a medicinal preparation and a method for the production thereof - Google Patents

Solid oral form of a medicinal preparation and a method for the production thereof Download PDF

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Publication number
WO2007105981A1
WO2007105981A1 PCT/RU2006/000237 RU2006000237W WO2007105981A1 WO 2007105981 A1 WO2007105981 A1 WO 2007105981A1 RU 2006000237 W RU2006000237 W RU 2006000237W WO 2007105981 A1 WO2007105981 A1 WO 2007105981A1
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WO
WIPO (PCT)
Prior art keywords
solid oral
antibodies
antibody
pharmaceutically acceptable
dilution
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/RU2006/000237
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English (en)
French (fr)
Russian (ru)
Inventor
Oleg Iliich Epshtein
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.)
Individual
Original Assignee
Individual
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
Priority to CN2006800540501A priority Critical patent/CN101415403B/zh
Priority to JP2009500312A priority patent/JP5551429B2/ja
Priority to LTEP06799634.8T priority patent/LT1997481T/lt
Priority to US12/282,614 priority patent/US9522116B2/en
Priority to PL06799634T priority patent/PL1997481T3/pl
Priority to DK06799634.8T priority patent/DK1997481T3/en
Priority to BRPI0621507-6A priority patent/BRPI0621507A2/pt
Priority to EA200801971A priority patent/EA200801971A1/ru
Priority to MX2008011811A priority patent/MX2008011811A/es
Priority to EP06799634.8A priority patent/EP1997481B1/en
Priority to AU2006340119A priority patent/AU2006340119B2/en
Priority to CA2645475A priority patent/CA2645475C/en
Application filed by Individual filed Critical Individual
Priority to ES06799634.8T priority patent/ES2651350T3/es
Publication of WO2007105981A1 publication Critical patent/WO2007105981A1/ru
Anticipated expiration legal-status Critical
Priority to ZA2008/08631A priority patent/ZA200808631B/en
Priority to US15/349,640 priority patent/US20170056499A1/en
Priority to CY20171101299T priority patent/CY1119682T1/el
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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0004—Homeopathy; Vitalisation; Resonance; Dynamisation, e.g. esoteric applications; Oxygenation of blood
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39591—Stabilisation, fragmentation
    • 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
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • 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]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/241—Tumor Necrosis Factors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies

Definitions

  • the invention relates to medicine and can be used for the technologically simple preparation of a solid oral antibody-based drug for the effective treatment of a pathological syndrome without significant side effects.
  • medications serums, immunoglobulins
  • antibodies used in therapeutic doses
  • these drugs are prepared in liquid dosage form for injection and injected into the body parenterally, since only with this method of administration the bioavailability of these drugs is ensured.
  • the invention is directed to the creation of a solid form of a drug based on antibodies suitable for oral administration. denia, and a technologically simple way to obtain a drug based on antibodies in an activated form prepared according to homeopathic technology in the form of tablets.
  • the solid oral form of the antibody-based drug product includes an effective amount of a carrier irrigated with water-alcohol dilution of antibodies in an activated form prepared by combining multiple serial dilutions of antibodies and external exposure, and pharmaceutically acceptable additives.
  • water-alcohol dilution contains, in an activated form, antibodies to an endogenous substance involved in the regulation or affecting the mechanisms of formation of a pathological syndrome, the activated form being prepared by repeated serial dilution and external exposure according to homeopathic technology.
  • the drug contains a neutral substance - lactose
  • a pharmaceutically acceptable additive contains a binder and a glidant.
  • the additionally solid oral form contains a neutral filler - lactose in an amount of 30 ⁇ 80 mass. % of the mass of solid oral form - tablets, while in the capacity of a binder contains microcrystalline cellulose in an amount of 10.0 ⁇ 15.0 mass. % of the mass of solid oral form - tablets, and as a moving substance - magnesium stearate in an amount of 0.8 ⁇ 1.2 mass. % by weight of solid oral form - tablets.
  • the activated form of antibodies is a mixture of various decimal and / or hundreds of water-alcohol homeopathic dilutions.
  • the method of obtaining a solid oral form of a drug based on antibodies involves the preparation of a water-alcohol dilution of antibodies in an activated form, obtained by combining multiple serial dilutions and external exposure using homeopathic technology, irrigation with a water-alcohol dilution of a neutral carrier in a fluidized - fluidized bed with simultaneous drying at a temperature not exceeding 35 0 C, mixing in pharmaceutically acceptable sequence with pharmaceutically acceptable additives, and subsequent tabletting — tablet formation by direct dry compression.
  • a neutral substance lactose, with a particle size of 150 to 250 microns, is used as a carrier.
  • the introduction into the solid dosage form of antibodies in the activated form provides the possibility of oral administration of a drug based on antibodies while maintaining biological activity.
  • the qualitative, quantitative, particle size and structural composition of the claimed ingredients provides the possibility of reliable formation of tablets directly dry pressing using a limited number of additives.
  • Polyclonal antibodies, monoclonal antibodies, and natural antibodies to a substance involved in the regulation or affecting the mechanisms of formation of a pathological syndrome are used to prepare a pharmaceutical substance.
  • Polyclonal antibodies that specifically bind to compounds of various classes — proteins, polynucleotides, oligosaccharides, glycolipids, etc., as well as interacting with low molecular weight substances (haptens) are obtained by active immunization of animals.
  • an antigen which is either an individually isolated high molecular weight substance, or is a synthetic conjugate - in the case of using haptens.
  • an antigen which is either an individually isolated high molecular weight substance, or is a synthetic conjugate - in the case of using haptens.
  • an antigen which is either an individually isolated high molecular weight substance, or is a synthetic conjugate - in the case of using haptens.
  • an antigen which is either an individually isolated high molecular weight substance, or is a synthetic conjugate - in the case of using haptens.
  • an antigen which is either an individually isolated high molecular weight substance, or is a synthetic conjugate - in the case of using haptens.
  • Monoclonal antibodies of various specificity interacting with both low molecular weight haptenes and epitopes of high molecular weight substances are obtained using hybridoma technology.
  • the initial stage of the process includes immunization, based on the principles already developed in the preparation of research institutes of polyclonal antisera. Further stages of the work include obtaining hybrid cells producing clones of antibodies of the same specificity. Their isolation in an individual form is carried out by the same methods as in the case of polyclonal antisera.
  • Natural antibodies to exogenous antigens and bioregulators of various nature are isolated from human blood serum by affinity chromatography.
  • a carrier with a covalently bound antigen which is either a hapten or a macromolecular compound, is used as an immunosorbent.
  • chromatography a population of antibodies with a narrow distribution of specificity and affinity is obtained.
  • Isolated antibodies to a substance or a medicinal product are subsequently diluted several times in combination with an external action, mainly vertical shaking, until an activated form is obtained, for example, by homeopathic potentiation technology (see, for example, W. Schwabe, Homeopathic medicines. Description and manufacturing manual , M., 1967, p. 12 - 38; or G. Keller, Homeopathy, M. "Medicine” 2000, part 1, p. 37 - 40).
  • homeopathic potentiation technology see, for example, W. Schwabe, Homeopathic medicines. Description and manufacturing manual , M., 1967, p. 12 - 38; or G. Keller, Homeopathy, M. "Medicine” 2000, part 1, p. 37 - 40).
  • a uniform decrease in concentration is carried out by sequentially diluting 1 volume part of the starting substance (antibodies) in 9 volume parts (for decimal dilution D) or in 99 volume parts (for hundredth dilution C) or in 999 volume parts (for thousandth dilution) of a neutral solvent - distilled water and / or 70% ethyl alcohol with multiple vertical shaking of each dilution obtained and the use of mainly separate containers for each subsequent dilution to obtain Nia required dilution.
  • External processing in the process of reducing the concentration can also be carried out by ultrasound or electromagnetic exposure, as well as other mechanical effects.
  • the granules of the neutral substance - lactose (milk) introduced into the fluidized bed are irrigated sugar) with a particle size of 150 ⁇ 250 microns prepared water-alcohol dilution (preferably hundred) of the activated form of antibodies with simultaneous drying at a temperature not exceeding 35 ° C.
  • the estimated amount of the prepared pharmaceutical substance - the active substance in the form of "saturated” lactose is loaded into the mixer and mixed with microcrystalline cellulose, introduced in an amount of 10.0 ⁇ 15.0 mass. % of the total mass of the load. Then “unsaturated” lactose is added to the mixture (if necessary, to reduce the cost and to simplify and speed up the technological process without reducing the effectiveness of the therapeutic effect by reducing the content of a pharmaceutical substance in a tablet: water-alcohol dilution of the activated form of antibodies) in an amount of 30–80 macc. % of the total mass of the load and magnesium stearate in an amount of 0.8 ⁇ 1.2 mass. % of the total mass of the load, and evenly mixed.
  • the obtained dry homogeneous mixture is sent to a tabletting machine, for example, tablet - Korsh press - XL 400, to form round tablets by direct dry pressing weighing 150 ⁇ 500 mg.
  • a tabletting machine for example, tablet - Korsh press - XL 400
  • the following is an example of obtaining a drug in the form of an activated form of polyclonal antibodies (antisera) to morphine, the process of which proceeds in several stages.
  • the step of obtaining the morphine-ovalbulin conjugate is the step of obtaining the morphine-ovalbulin conjugate.
  • a solution of 50 mg (0.001 mmol) of ovalbulin in 5.0 ml of distilled water is mixed with 2.0 ml of dimethylformamide containing 15.0 mg (0.039 mmol) of morphine 6-hemicycin, and a solution of 15 mg (0.055 mmol) is added dropwise.
  • water-soluble carbodiamide in 3 ml of distilled water was incubated for 5 hours at 4 ° C.
  • the resulting conjugate was isolated by gel chromatography on a Sephadex G25 column and lyophilized.
  • the amount of attached morphine is calculated from the UV spectra of the starting protein and the resulting conjugate from the change in absorbance at 280 nm. According to the UV spectra, the synthesized conjugate contains 12–15 moles of hapten per mole of protein.
  • the immunization of “Blue Blue” rabbits weighing no more than 2 kg is carried out cyclically with a 10-day interval. The maximum number of injections is four.
  • the conjugate is injected into the front and hind limbs in the region of the articular lymph nodes in an amount of 1 mg per immunization.
  • the antigen is pre-dissolved in 1 ml of complete Freund's adjuvant.
  • the volume of the mixture for immunization is 2 ml.
  • Rabbit blood serum was obtained by centrifugation at 100Og for 10 minutes at room temperature, after which chloroform was added as a preservative to a final concentration of 13%.
  • the resulting antiserum is checked by enzyme-linked immunosorbent assay for the presence of specific antibodies to morphine, the detection of which is carried out using the conjugate of antispecies antibodies labeled with the enzyme.
  • antiserum contains specific antibodies at a dilution of 1: 1000 ⁇ 1: 25000.
  • the ⁇ -globulin fraction is isolated from the obtained antiserum.
  • protein precipitation with 50% ammonium sulfate is used, followed by washing the precipitate with 30% saline solution, centrifugation and dialysis against phosphate buffer.
  • the fraction thus prepared containing specific antibodies to this antigen is used in the next step to prepare a drug.
  • the step of obtaining an activated form of antibodies to morphine is a step of obtaining an activated form of antibodies to morphine.
  • 0.5 ml of the fraction of ⁇ -globulin antiserum is placed in an E-6 container. 4.5 ml of distilled water are added, shaken 10 times, 5 ml of the 1st hundredth dilution are obtained. Then 0.05 ml of the 1st hundredth dilution is placed in an E-6 2 container, 4.95 ml of distilled water is added, shaken 10 times, 5.0 ml of the 2nd hundredth dilution is obtained. Similarly, the 2nd hundredth dilution is prepared from the 3rd to 29th hundredth dilution. The final 30th hundredth dilution is obtained by diluting the 29th in 70% ethanol.
  • the resulting water-alcohol solution is used for fluidized bed irrigation of particles of a neutral carrier - lactose (milk sugar) in the preparation of a pharmaceutical substance - the active substance in the form of "saturated" lactose, which is the basis for the formation of direct oral compression of a solid oral form (round tablets, mainly , weighing 240 and 300 mg) of the claimed drug.
  • a neutral carrier - lactose milk sugar

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Reproductive Health (AREA)
  • Addiction (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Rheumatology (AREA)
  • Endocrinology (AREA)
  • Pain & Pain Management (AREA)
  • Psychiatry (AREA)
  • Gynecology & Obstetrics (AREA)
  • Neurosurgery (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PCT/RU2006/000237 2006-03-13 2006-05-16 Solid oral form of a medicinal preparation and a method for the production thereof Ceased WO2007105981A1 (en)

Priority Applications (16)

Application Number Priority Date Filing Date Title
JP2009500312A JP5551429B2 (ja) 2006-03-13 2006-05-16 固体の経口投与形態の医薬組成物、及びその製造方法
LTEP06799634.8T LT1997481T (lt) 2006-03-13 2006-05-16 Medicininio preparato solidinė peroralinė forma ir jos gavimas
US12/282,614 US9522116B2 (en) 2006-03-13 2006-05-16 Solid oral form of a medicinal preparation and a method for the production thereof
PL06799634T PL1997481T3 (pl) 2006-03-13 2006-05-16 Stała postać doustna preparatu leczniczego i sposób jego wytwarzania
DK06799634.8T DK1997481T3 (en) 2006-03-13 2006-05-16 Solid oral form of a medical composition and method of preparation thereof
BRPI0621507-6A BRPI0621507A2 (pt) 2006-03-13 2006-05-16 método para a produção de uma forma oral sólida de uma preparação medicinal baseada em anticorpo e forma de dosagem sólida para a administração em um sujeito humano
EA200801971A EA200801971A1 (ru) 2006-03-13 2006-05-16 Твердая оральная форма лекарственного препарата и способ получения твердой оральной формы лекарственного препарата
EP06799634.8A EP1997481B1 (en) 2006-03-13 2006-05-16 Solid oral form of a medicinal preparation and a method for the production thereof
MX2008011811A MX2008011811A (es) 2006-03-13 2006-05-16 Forma oral solida de una preparacion medicinal y un metodo para la produccion de la misma.
CN2006800540501A CN101415403B (zh) 2006-03-13 2006-05-16 药物制剂的固体口服剂形式及其制备方法
CA2645475A CA2645475C (en) 2006-03-13 2006-05-16 Solid oral form of a medicinal preparation and a method for the production thereof
AU2006340119A AU2006340119B2 (en) 2006-03-13 2006-05-16 Solid oral form of a medicinal preparation and a method for the production thereof
ES06799634.8T ES2651350T3 (es) 2006-03-13 2006-05-16 Forma oral sólida de una preparación medicinal y un método para la producción de la misma
ZA2008/08631A ZA200808631B (en) 2006-03-13 2008-10-09 Solid oral form of a medicinal preparation and a method for the production thereof
US15/349,640 US20170056499A1 (en) 2006-03-13 2016-11-11 Solid oral form of a medicinal preparation and a method for the production thereof
CY20171101299T CY1119682T1 (el) 2006-03-13 2017-12-12 Απο του στοματος στερεα μορφη ενος φαρμακευτικου παρασκευασματος και μια μεθοδος για την παραγωγη αυτης

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
RU2006107580/15A RU2309732C1 (ru) 2006-03-13 2006-03-13 Спрессованная твердая оральная форма лекарственного препарата и способ получения твердой оральной формы лекарственного препарата
RU2006107580 2006-03-13

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US12/282,614 A-371-Of-International US9522116B2 (en) 2006-03-13 2006-05-16 Solid oral form of a medicinal preparation and a method for the production thereof
US15/349,640 Division US20170056499A1 (en) 2006-03-13 2016-11-11 Solid oral form of a medicinal preparation and a method for the production thereof

Publications (1)

Publication Number Publication Date
WO2007105981A1 true WO2007105981A1 (en) 2007-09-20

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Family Applications (1)

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PCT/RU2006/000237 Ceased WO2007105981A1 (en) 2006-03-13 2006-05-16 Solid oral form of a medicinal preparation and a method for the production thereof

Country Status (21)

Country Link
US (2) US9522116B2 (enExample)
EP (1) EP1997481B1 (enExample)
JP (1) JP5551429B2 (enExample)
KR (1) KR20080109017A (enExample)
CN (1) CN101415403B (enExample)
AU (1) AU2006340119B2 (enExample)
BR (1) BRPI0621507A2 (enExample)
CA (1) CA2645475C (enExample)
CY (1) CY1119682T1 (enExample)
DK (1) DK1997481T3 (enExample)
EA (1) EA200801971A1 (enExample)
ES (1) ES2651350T3 (enExample)
HU (1) HUE035265T2 (enExample)
LT (1) LT1997481T (enExample)
MX (1) MX2008011811A (enExample)
PL (1) PL1997481T3 (enExample)
PT (1) PT1997481T (enExample)
RU (1) RU2309732C1 (enExample)
UA (1) UA92076C2 (enExample)
WO (1) WO2007105981A1 (enExample)
ZA (1) ZA200808631B (enExample)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9522116B2 (en) 2006-03-13 2016-12-20 Oleg Iliich Epshtein Solid oral form of a medicinal preparation and a method for the production thereof
WO2021040570A1 (en) 2019-08-29 2021-03-04 Oleg Iliich Epshtein Medicament and method for treating infectious diseases
WO2025088452A1 (en) 2023-10-24 2025-05-01 Epshtein Oleg Ilyich Artificial substance and method of its preparation

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2181297C2 (ru) * 2000-06-20 2002-04-20 Эпштейн Олег Ильич Способ лечения патологического синдрома и лекарственное средство
UA76638C2 (en) 2002-08-02 2006-08-15 Oleh Illich Epshtein Homeopathic medication based on anti-interferon antibodies and method for treating a pathological syndrome associated with interferon
MX2008015621A (es) 2006-06-06 2009-03-06 Oleg Iliich Epshtein Agente medicinal para el tratamiento de obesidad, diabetes y enfermedades relacionadas con la tolerancia deteriorada de glucosa.
RU2525155C2 (ru) * 2010-07-15 2014-08-10 Общество С Ограниченной Ответственностью "Научно-Производственная Фирма "Материа Медика Холдинг" Способ лечения хронической сердечной недостаточности и фармацевтическая композиция для комплексной терапии хронической сердечной недостаточности
RU2525156C2 (ru) * 2010-07-15 2014-08-10 Общество С Ограниченной Ответственностью "Научно-Производственная Фирма "Материа Медика Холдинг" Способ лечения и профилактики артериальной гипертензии и фармацевтическая композиция для лечения артериальной гипертензии
RU2523557C2 (ru) * 2010-07-15 2014-07-20 Общество С Ограниченной Ответственностью "Научно-Производственная Фирма "Материа Медика Холдинг" Способ лечения вегетососудистой дистонии и фармацевтическая композиция для лечения вегетососудистой дистонии
RU2531048C2 (ru) * 2010-07-21 2014-10-20 Мапикс Эс.Эй.Ар.Эл. Лекарственное средство для уменьшения резистентности к инсулину и лечения сахарного диабета и способ повышения эффективности лечения сахарного диабета инсулином и/или гипогликемическими препаратами
RU2522499C2 (ru) * 2010-07-27 2014-07-20 Олег Ильич Эпштейн Лекарственное средство для лечения инфекционных заболеваний, сопровождающихся нейротоксическими нарушениями, и способ лечения инфекционных заболеваний, сопровождающихся нейротоксическими нарушениями
PH12013500107A1 (en) 2010-07-15 2013-03-11 Oleg Iliich Epshtein A method of increasing the effect of an activated-potentiated form of an antibody
CA2805091A1 (en) * 2010-07-15 2012-01-19 Oleg Iliich Epshtein Pharmaceutical compositions comprising a homopathically potentized form of an antibody to human cannabinoid receptor
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EA200801971A1 (ru) 2009-02-27
ES2651350T3 (es) 2018-01-25
BRPI0621507A2 (pt) 2011-12-13
KR20080109017A (ko) 2008-12-16
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CY1119682T1 (el) 2018-04-04
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CN101415403B (zh) 2013-07-10
EP1997481B1 (en) 2017-09-13
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US20170056499A1 (en) 2017-03-02
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PL1997481T3 (pl) 2018-02-28
EP1997481A1 (en) 2008-12-03
US20090148521A1 (en) 2009-06-11
LT1997481T (lt) 2018-02-12
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