WO2006033453A1 - Amplificateur d'activité pour un agent de type interféron - Google Patents

Amplificateur d'activité pour un agent de type interféron Download PDF

Info

Publication number
WO2006033453A1
WO2006033453A1 PCT/JP2005/017907 JP2005017907W WO2006033453A1 WO 2006033453 A1 WO2006033453 A1 WO 2006033453A1 JP 2005017907 W JP2005017907 W JP 2005017907W WO 2006033453 A1 WO2006033453 A1 WO 2006033453A1
Authority
WO
WIPO (PCT)
Prior art keywords
interferon
glycine
agonist
agent
ifn
Prior art date
Application number
PCT/JP2005/017907
Other languages
English (en)
Japanese (ja)
Inventor
Nobuhiro Sato
Yoshiyuki Takei
Kenichi Ikejima
Sonoko Ishizaki
Original Assignee
Juntendo Educational Foundation
Ajinomoto Co., Inc.
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 Juntendo Educational Foundation, Ajinomoto Co., Inc. filed Critical Juntendo Educational Foundation
Priority to JP2006536439A priority Critical patent/JPWO2006033453A1/ja
Publication of WO2006033453A1 publication Critical patent/WO2006033453A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/21—Interferons [IFN]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • 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
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to an activity enhancer of an interferon agonist that has an activity enhancing activity of an interferon agonist, a side effect alleviator that reduces the side effects of interferon agonist treatment, a pharmaceutical comprising a combination of glycine and an interferon agonist, and
  • the present invention relates to pharmaceutical compositions thereof.
  • Interferon is a cytokine with various biological activities such as antiviral action, cell growth suppression production, and immunomodulation action.
  • IFN Interferon
  • HCV hepatitis C virus
  • Ribavirin (R i b a V i r i n, hereinafter also referred to as R i b) is an antiviral agent that exhibits antiviral activity with a different mechanism of action from IFN. Although it has no effect on HCV alone, combination therapy with IFN and Rib improves the overall efficacy to about 50% for all cases and to about 30% for intractable patients (Japanese liver) (See the Society edition, Chronic hepatitis treatment guide (Bunkodo), p 30, p 34 (2004)). However, it has not yet reached an effective therapeutic effect for all patients. Therefore, there is currently a need for an IFN activity enhancer that has even better effects.
  • Glycine on the other hand, is known to have anti-inflammatory, cytoprotective, and immunoregulatory effects (Z. Zhong et al.), Current-Pione 'in' Clinical. & Metabolic Care (Refer to Curr Op in Clin Nutra Me tab Carre.) 6, 229-40 (2003)), enhances IFN activity and reduces side effects of IFN There is no report that it has the action to do. Disclosure of the invention
  • the problem to be solved by the present invention is to reduce the side effects of reducing the side effect of an excellent IFN agonist and the excellent activity enhancer of IFN agonist that enhances the activity of IFN agonist during the treatment of IFN agonist Is to provide an agent.
  • glycine enhances the activity of an IFN agonist and that glycine alone also exhibits an IFN-like activity.
  • the present invention is as follows.
  • An interferon active substance potentiator comprising glycine as an active ingredient.
  • An antiviral agent comprising the interferon agonist activity enhancer described in (1) or (2) above.
  • a therapeutic agent for viral hepatitis comprising the interferon agonist activity enhancer according to (1) or (2) above.
  • a therapeutic agent for cirrhosis caused by viral hepatitis comprising the activity enhancer of an interferon acting substance described in (1) or (2) above.
  • An antitumor agent comprising the activity enhancer of an interferon acting substance described in (1) or (2) above.
  • a therapeutic agent for an autoimmune disease comprising the interferon-acting substance activity enhancer according to (1) or (2) above.
  • a food composition comprising the interferon active substance activity enhancer according to (1) or (2) above.
  • An agent for reducing side effects in the treatment of an interferon active substance comprising glycine as an active ingredient.
  • interferon agonist treatment is an interferon agonist treatment for viral hepatitis.
  • interferon agonist treatment is a treatment including a combination of an interferon agonist and a ribavirin agonist.
  • a food composition comprising the side effect reducing agent according to any one of (9) to (13).
  • An antiviral agent comprising glycine as an active ingredient.
  • a therapeutic agent for viral hepatitis comprising glycine as an active ingredient.
  • a pharmaceutical comprising a combination of glycine and an interferon active substance.
  • a pharmaceutical kit comprising a combination of glycine and an interferon active substance as active ingredients as active ingredients.
  • a pharmaceutical kit characterized by combining, as active ingredients, glycine, an interferon active substance and a lipavirin acting substance as a simple agent.
  • An interferon-inducible gene expression enhancer comprising glycine as an active ingredient.
  • a method for enhancing the activity of an interferon agonist comprising administering an effective amount of glycine.
  • a method of reducing side effects in interferon agonist treatment comprising administering an effective amount of glycine.
  • a method for enhancing the expression of an interferon-inducible gene comprising administering an effective amount of glycine.
  • Fig. 1 shows the increased expression of IFN-inducible gene (PKR) in PBMC by glycine administration. (Average soil standard deviation: * ** P ⁇ 0.005: t test)
  • Figure 2 shows the increased expression of the IFN-inducible gene (2-5AS1) in PBMC by glycine administration. (Average soil standard deviation: * P ⁇ 0.05, ** P ⁇ 0.01: t test)
  • Figure 3 shows the increased expression of IFN-inducible gene (PKR) in the liver by glycine administration. (Average value of 2 cases in each group)
  • Figure 4 shows the increase in the expression of IFN-inducible gene (2_5 A S 1) in the liver by glycine administration. (Average value of 2 cases in each group) The best mode for carrying out the invention
  • glycine is not necessarily used as a free amino acid, and may be used in the form of an inorganic acid salt, an organic acid salt, an ester that can be hydrolyzed in vivo, or the like. Alternatively, it may be used in the form of peptides in which two or more glycines or other amino acids are peptide-bonded.
  • the active enhancer of the IFN active substance of the present invention may be a simple glycine, but may contain a pharmaceutical carrier and a general food material described below.
  • the IFN-acting substance in the present invention is not particularly limited as long as it is a substance that exhibits an IFN-like action in vivo in addition to IFN.
  • I FN include I FN- ⁇ , I FN—; 3 and I FN- ⁇ , a chemical modification of IFN, and the like. It is said that there are more than 20 subtypes of IFN- ⁇ , which can be broadly divided into those consisting of 165-166 amino acids and those consisting of 172 amino acids. Molecular weight Is between 1.7 and 230,000, with the former having sugar chains but the latter not having sugar chains.
  • IFN- ⁇ has a natural type and a recombinant type produced in E. coli by genetic recombination. The latter does not have a sugar chain.
  • Natural type I FN-a preparations include OVF (registered trademark), I FN- ⁇ Mochida, and Sumiferon (registered trademark) (2.5 million to 6 million international unit doses per adult).
  • Genetically modified IF ⁇ — ⁇ preparations include Advaferon (registered trademark), Oral ferroon (registered trademark), Canferon (registered trademark) ⁇ , Intron (registered trademark) ⁇ , etc. (3 million adults per day) ⁇ 18 million international unit administration).
  • I FN—] 3 consists of 166 amino acids and has no subtypes.
  • Natural type I FN— preparations include FERRON (registered trademark), I FN] 3 Mochida (1 million to 3 million international daily doses for adults), and recombinant IFN— preparations include BETA FERON (registered trademark) (Adult daily administration of 8 million international units).
  • Natural type I FN— y preparations include O-Gamma (registered trademark) (administered 1 million international units per day for adults), and genetically modified I FN— ⁇ preparations include bio-gamma (registered trademark), Imnomax (registered trademark). ) One gamma (2 to 4 million international unit doses per day for adults).
  • the chemical modification of the I FN were modified inter Feron with polyethylene glycol (PEG), for example PEG- in interferon one alpha 2 a (Bae Gashisu (TM) (adult 180 mu g administered per day)) And PEG-interferon- ⁇ 2 b (PEG-Intron (registered trademark) (1.5 g dose per adult IS)).
  • PEG polyethylene glycol
  • the IFN-acting substance may be any substance that induces IFN-like biological activity, and does not necessarily have to have the same amino acid sequence as IFN. Further, it may be an antibody, a peptide, or a small molecule. Of these, IFN preparations are preferred, and IFN-a preparations are particularly preferred.
  • Enhancement of the activity of IFN agonists means enhancing the effect of IFN agonist treatment, and the resulting improvement in the efficiency of patients treated with IFN agonist, shortening of treatment period, IFN agonist Including dose reduction.
  • PKR double-stranded RNA-dependent protein
  • Kinase Kinase
  • 2-5AS 1 oligoadenylate synthase 1).
  • the activity-enhancing activity of IFN agonists can be confirmed by examining their expression levels.
  • antiviral activity which is one of the IFN biological activities, is exhibited by inducing the expression of PKR, 2-5 AS1, so if the expression of these genes is enhanced, an IFN agonist It is clear that the activity of is enhanced.
  • IFN agonist treatment refers to treatment of a disease by administering an IFN agonist.
  • the IFN agonist treatment in the present invention includes the case where an IFN agonist and other drugs are used in combination, for example, a combination therapy of an IFN agonist and a Rib agonist.
  • R ib In addition to R ib, R ib analogs such as V ir am idine (Watson et al., Current O inionininvestigationa ldrugs 2002, 3, (5) 680-683)
  • the substance is not particularly limited as long as it exhibits a Rib-like action that enhances the antiviral effect of interferon in vivo.
  • the pharmaceutical composition containing the activity enhancer of the IFN agonist of the present invention can be used as an antiviral agent, a viral hepatitis therapeutic agent, an antitumor agent, or an autoimmune disease therapeutic agent.
  • the viral disease to be treated is preferably a disease for which an IFN agonist treatment is performed, for example, hepatitis B virus (HBV), hepatitis C virus (HCV), HT L V -1 virus, preferably hepatitis C virus (HCV) disease treatment.
  • viremia for the treatment of viral hepatitis, it can be used to improve viremia of HB e antigen positive and DNA polymerase positive active hepatitis B, viremia in chronic hepatitis C, especially chronic C Useful for treating patients with hepatitis. Furthermore, it can be used for cirrhosis caused by viral hepatitis.
  • chronic myelogenous leukemia, renal cancer, multiple myeloma, hairy cell leukemia, subacute sclerosing panencephalitis, HTLV-1 myelopathy, cutaneous malignant melanoma, glioblastoma, medulloblastoma Can be used for the treatment of astrocytoma, etc.
  • an autoimmune disease therapeutic agent it can be used for the treatment of multiple sclerosis and the like.
  • the agent for reducing side effects in the treatment of IFN agonists according to the present invention is an agent for reducing side effects that reduces the side effects of IFN agonist treatment, comprising glycine as an active ingredient.
  • the side effect reducing agent of the present invention may be glycine alone, but may contain a pharmaceutical carrier and a general food material described below.
  • IFN agonist treatment is interstitial pneumonia, pulmonary fibrosis, depression, suicide planning, disturbance of consciousness, convulsions, disorientation, delirium, confusion, hallucinations, acupuncture, etc.
  • the Rib agent may be used in combination, but hemolytic anemia, general malaise, depression, Psychiatric symptoms such as insomnia, neurological symptoms such as dizziness, digestive symptoms such as decreased appetite and nausea, muscle pain, eczema, and sensation are also included in the reduction of side effects of the present invention.
  • glycine can be used as an antiviral agent or a viral hepatitis therapeutic agent alone or in combination with other antiviral agents or hepatitis therapeutic agents.
  • viral diseases that are suitable for treatment include hepatitis B virus (H B V), hepatitis C virus (HCV), and HTLV-1 virus.
  • H B V hepatitis B virus
  • HCV hepatitis C virus
  • HTLV-1 virus hepatitis B virus
  • HBe antigen-positive and DNA polymerase-positive active hepatitis B and viremia in chronic hepatitis C.
  • it can be used for cirrhosis caused by viral hepatitis.
  • Antiviral agents to be combined with glycine include the above-mentioned IFN active substances, Rib active substances, synthetic drugs such as ramipudine, etc.
  • ursodeoxy Examples include cholic acid and Sho-saiko-to.
  • the medicament of the present invention includes either a pharmaceutical composition containing glycine and an IFN agent, or a formulation in which glycine and an IF agent are separately formulated.
  • the medicament of the present invention includes chronic hepatitis B, chronic hepatitis C, chronic myelogenous leukemia, renal cancer, multiple myeloma, hairy cell leukemia, subacute sclerosing panencephalitis, It can be used for diseases such as cutaneous malignant melanoma, glioblastoma, medulloblastoma, astrocytoma. Preparation>
  • the pharmaceutical of the present invention and the drug such as an activity enhancer of an IFN active substance, a side effect reducing agent, and an antiviral agent are, for example, a pharmacologically acceptable carrier for glycine or (and) an IFN active substance according to a method known per se.
  • a pharmaceutical composition such as injections, tablets, granules, fine granules, powders, capsules, creams, suppositories, orally or parenterally (eg, topical, rectal, intravenous administration, etc.) Can be administered.
  • the activity enhancer and side effect reducing agent of the pharmaceutical and IFN active substance can be formulated as various preparations by a method known per se using a pharmacologically acceptable carrier or additive.
  • the preparation include liquid preparations such as injections (for intramuscular injection and intravenous injection), tube preparations, solid preparations such as powders, fine granules, granules, tablets and capsules.
  • Examples of the carrier for the preparation include lactose, glucose, D-mannitol, starch, crystalline cellulose, calcium carbonate, kaolin, starch, gelatin, hydroxypropylcellulose, hydroxypropylmethylenocellulose, polyvinylpyrrolidone, ethanolanol.
  • the dose of glycine varies depending on the patient's condition, age, administration method, etc. Usually about 0.1 to 50 g ZB, preferably about 2.5 to 40 g Z days, more preferably about 3 to 30 g Z days, and this is divided into 1 to 5 times as necessary. To administer.
  • the dose of the IFN active substance varies depending on the patient's condition, age, and administration method.Adult Adult daily dose is about 1 million to 200,000 international units, or adult daily dose is 20 to 40. Set to about 0 ⁇ g.
  • the dose of Rib agonist should be about 20 to 200 mg as the daily dose for adults.
  • glycine and IFN active substance and Z or Rib active substance may be prepared separately, respectively, or a pharmaceutical composition containing glycine and IFN active substance and / or Rib active substance at the same time. It is good also as a compounding agent which is a thing.
  • the amount of glycine in one preparation is usually about 0.02 to 50 g, preferably about 0.4 to 40 g, more preferably about 0.6 to 30 g.
  • the amount of I FN active substance and Z or Rib active substance in one preparation should be set for each drug.
  • the ratio of glycine to IFN active substance in the combination is 2 x 10 4 to 2 x 10 8 international units for IFN acting substance or 0.: ⁇ 40 0 ⁇ ⁇ g for IFN acting substance. Yes, preferably 2.5 x 10 4 to 8 x 10 6 international units or 0.5 to 160 zg of IFN active agent per 0.5 g of glycine, more preferably 0.5 to 160 zg of IFN active agent.
  • the IFN agonist is 3 xl 0 4 to 7 xl 0 6 international units or the IFN agonist is 0.7 to 1 30 ⁇ g.
  • the present invention can also provide a pharmaceutical composition containing an Rib agonist in addition to glycine and an IFN agonist.
  • the pharmaceutical composition of the present invention contains glycine, an IFN active substance and an Rib active substance
  • the ratio of the glycine, the IFN active substance and the Rib active substance in the pharmaceutical composition is 1 g of glycine
  • the IFN active substance 2 x 10 4 to 2 X 10 8 international units or I FN agonist is 0.4 to 4000 ⁇ g
  • Rib agonist is 4 mg to 20 g, preferably IFN action against glycine lg
  • the substance is 2.5 xl 0 4 to 8 xl 0 6 international units or I FN active agent is 0.5 to 160 jug
  • Rib active agent is 5 to 800 mg, more preferably, for glycine lg IFN agonists are 3 X 10 4 to 7 X 10 6 international units or IFN agonists are 0.7 to 130 ⁇
  • Rib agonists are
  • glycine and the IFN and / or Rib agents are in separate formulations, glycine can be administered alone to treat the disease or in combination with the IFN and / or Rib agents For the purpose of It can be administered either simultaneously or before or after administration of the IFN agonist.
  • the administration method and dose at the time of concomitant use are appropriately determined according to the type and effect of the concomitant drug.
  • the time lag varies depending on the active ingredient, dosage form, and method of administration.
  • glycine when glycine is administered first, glycine The method includes administering an IFN agonist within 5 minutes to 14 days after administration, preferably within 10 minutes to 7 days.
  • glycine is administered within 5 minutes to 120 hours or less, preferably within 10 minutes to 80 hours after administration of an IFN agonist.
  • the dose (intake amount) of glycine which is an active ingredient used in the present invention, as an active ingredient of a drug used for the purpose of treatment or prevention of various disease abnormalities targeted by the present invention. Since the above calculation range has been determined, for the purposes other than this, for example, for the need of normal eating habits, or for the treatment of other diseases, this is used for the above calculation. It is not necessary to include it.
  • the activity enhancer or side effect reducing agent of the IFN active substance of the present invention may be packaged together, for example, in combination with an effective amount of IFN preparation, Rib preparation, or both IFN preparation and Rib preparation. Can be used as a pharmaceutical kit.
  • the activity enhancer and / or side effect reducing agent of the IFN-active substance of the present invention can be contained in a food composition.
  • food materials such as nutritional components and additives that are preferable as a food composition may be added and prepared by a conventional method.
  • the interferon-inducible gene expression enhancer of the present invention is an enhancer that enhances the expression of an interferon-inducible gene, characterized by using glycine as an active ingredient.
  • the interferon-inducing gene in the present invention is not particularly limited as long as the production is induced by interferon, and examples thereof include PKR gene and 2 15 AS 1.
  • the description includes a so-called Noh book that describes the purpose of use, efficacy and administration method, etc. .
  • Chronic hepatitis was induced by a total of 5 subcutaneous injections One hour after administration on the final day, glycine 2 g / kg or physiological saline 1 Om 1 / kg was administered orally to each of 4 animals 24 hours Thereafter, 2.5 ml of blood was collected from the inferior vena cava of all rats under ether anesthesia, mixed with 2.5 ml of PBS, and peripheral blood mononuclear cells were collected using Lympho 1 yte—Rat (Cosmo Bio).
  • PBMC Human Recom inant IF—a (Cell Signaling 1 echno 1 ogy)) was added to a final concentration of 1 OOOI UZm1.
  • ISOGEN Natural Gene
  • DNTPmix, O1igo dT, DTT, and reverse transcriptase were added to the extracted RNA, and cDNA was synthesized using a gene amplification apparatus.
  • IFN-inducible gene PLR and 2-5 AS 1
  • SYBR green PCR Mastermi SYBR green PCR Mastermi (Applied Biosyst ems) as control
  • TaqMan PCR amplification The gene expression level was quantified using a detection system (AB I 7700). The results were expressed as the ratio of the expression level of the PKR gene or 2-5 AS 1 gene to the GAPDH gene expression level. Figures 1 and 2 show the results.
  • PKR and 2_5 AS1 which are IFN-inducible genes
  • IFN IFN-inducible genes
  • the IFN active substance activity enhancer or IFN active substance treatment side effect reducing agent of the present invention When used in combination with an IFN active substance, side effects caused by the IFN active substance are reduced, and remarkable efficiency is significantly improved. it can. Therefore, the dose of IFN agonist can be reduced or the administration period can be shortened, and the indication can be expanded to patients who could not be indicated due to side effects. In addition, by reducing the side effects, it becomes possible to select a dosage form that increases the dosage or prolongs the administration period, which can broaden the scope of treatment.
  • the activity enhancer or side effect reducing agent for the IFN active substance of the present invention can be used simultaneously.
  • the side effects of Rib agonists as well as FN agonists can be reduced. Therefore, the indication can be extended to patients who had to give up or discontinue treatment due to side effects of Rib agonists.
  • glycine since glycine also exhibits an IFN-like action even when administered alone, it does not only enhance the activity of the IFN agonist or reduce the side effects, but also the IFN agonist and / or Rib agonist. It is possible to reduce the dose itself, and in some cases, to replace the Rib active substance in the FN active substance combination therapy with glycine, or to treat a viral disease containing glycine alone as an active ingredient.
  • the FN agonist and Rib agonist are important therapeutic agents for viral diseases represented by viral hepatitis
  • the present invention has not always been satisfactory in terms of side effects and remarkable efficiency. It is extremely useful for further improving the outcome of IFN agonist treatment.
  • the IFN-inducible gene expression enhancer of the present invention itself can be used as an experimental reagent in the fields of physiology and biochemistry in addition to its use as a medicament as described above.
  • This application is based on Japanese Patent Application No. 2004-275997 filed in ⁇ , the contents of which are incorporated in full herein.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Virology (AREA)
  • Epidemiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Mycology (AREA)
  • Zoology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un amplificateur d'activité et/ou un agent diminuant les effets secondaires pour un agent de type IFN contenant de la glycine comme ingrédient actif lequel est un excellent amplificateur d'activité et/ou agent diminuant les effets secondaires pour un agent de type IFN dans la mesure où il est capable d'accroître l'activité de l'agent de type IFN et/ou de diminuer les effets secondaires de celui-ci dans une thérapie utilisant l'agent de type IFN. L'invention concerne également un agent antiviral, un remède contre l'hépatite virale, un agent anti-tumeur, un remède contre les maladies auto-immunes, une composition d'aliment et ainsi de suite contenant l'amplificateur d'activité et/ou l'agent diminuant les effets secondaires pour un agent de type IFN.
PCT/JP2005/017907 2004-09-22 2005-09-21 Amplificateur d'activité pour un agent de type interféron WO2006033453A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2006536439A JPWO2006033453A1 (ja) 2004-09-22 2005-09-21 インターフェロン作用物質の活性増強剤

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2004275997 2004-09-22
JP2004-275997 2004-09-22

Publications (1)

Publication Number Publication Date
WO2006033453A1 true WO2006033453A1 (fr) 2006-03-30

Family

ID=36090197

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2005/017907 WO2006033453A1 (fr) 2004-09-22 2005-09-21 Amplificateur d'activité pour un agent de type interféron

Country Status (2)

Country Link
JP (1) JPWO2006033453A1 (fr)
WO (1) WO2006033453A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007013677A1 (fr) * 2005-07-27 2007-02-01 Ajinomoto Co., Inc. Potentialisateur pour substance ayant un effet semblable à celui de l'interféron
JP2009178057A (ja) * 2008-01-29 2009-08-13 Miyazakiken Sangyo Shien Zaidan インターフェロンとリバビリンとの併用治療効果の検出方法および検出キット
JP2011016728A (ja) * 2009-07-07 2011-01-27 Yamaguchi Univ 炎症性疾患の予防剤および／または治療剤
WO2021009332A1 (fr) * 2019-07-18 2021-01-21 Enyo Pharma Procédé pour diminuer les effets secondaires de l'interféron

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09216831A (ja) * 1995-06-12 1997-08-19 Otsuka Pharmaceut Co Ltd 抗ウイルス剤
JPH10506640A (ja) * 1995-05-19 1998-06-30 シェーリング コーポレイション Ｃ型肝炎の処置のためのリバビリンおよびインターフェロンαの使用
JPH10203972A (ja) * 1997-01-28 1998-08-04 Novartis Nutrition Ag アミノ酸を用いた免疫調節
JP2001226287A (ja) * 2000-02-17 2001-08-21 Sumitomo Pharmaceut Co Ltd 安定な注射用製剤
WO2003006053A1 (fr) * 2001-07-09 2003-01-23 Schering Aktiengesellschaft Preparations d'interferon-$g(b) humain
WO2003030613A2 (fr) * 2001-10-05 2003-04-17 Intermune, Inc. Procedes de traitement de la fibrose hepatique et de l'infection par le virus de l'hepatite c
JP2003342193A (ja) * 2002-05-30 2003-12-03 Otsuka Pharmaceut Co Ltd 注射用製剤

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10506640A (ja) * 1995-05-19 1998-06-30 シェーリング コーポレイション Ｃ型肝炎の処置のためのリバビリンおよびインターフェロンαの使用
JPH09216831A (ja) * 1995-06-12 1997-08-19 Otsuka Pharmaceut Co Ltd 抗ウイルス剤
JPH10203972A (ja) * 1997-01-28 1998-08-04 Novartis Nutrition Ag アミノ酸を用いた免疫調節
JP2001226287A (ja) * 2000-02-17 2001-08-21 Sumitomo Pharmaceut Co Ltd 安定な注射用製剤
WO2003006053A1 (fr) * 2001-07-09 2003-01-23 Schering Aktiengesellschaft Preparations d'interferon-$g(b) humain
WO2003030613A2 (fr) * 2001-10-05 2003-04-17 Intermune, Inc. Procedes de traitement de la fibrose hepatique et de l'infection par le virus de l'hepatite c
JP2003342193A (ja) * 2002-05-30 2003-12-03 Otsuka Pharmaceut Co Ltd 注射用製剤

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CASTRO PM ET AL: "Application of a statistical design to the optimization of culture medium for recombinant interferon-gamma production by Chinese hamster ovary cells.", APPL MICROBIOL BIOTECHNOL., vol. 38, no. 1, 1992, pages 84 - 90, XP002995069 *
YEH SL ET AL: "Effects of glutamine-supplement total parenteral nutrition on cytokine production and T cell population in septic rats.", J PARENTER ENTERAL NUTR., vol. 25, 2001, pages 269 - 274, XP002995068 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007013677A1 (fr) * 2005-07-27 2007-02-01 Ajinomoto Co., Inc. Potentialisateur pour substance ayant un effet semblable à celui de l'interféron
JP2009178057A (ja) * 2008-01-29 2009-08-13 Miyazakiken Sangyo Shien Zaidan インターフェロンとリバビリンとの併用治療効果の検出方法および検出キット
JP2011016728A (ja) * 2009-07-07 2011-01-27 Yamaguchi Univ 炎症性疾患の予防剤および／または治療剤
WO2021009332A1 (fr) * 2019-07-18 2021-01-21 Enyo Pharma Procédé pour diminuer les effets secondaires de l'interféron
CN114173784A (zh) * 2019-07-18 2022-03-11 埃尼奥制药公司 降低干扰素的副作用的方法
CN114173784B (zh) * 2019-07-18 2023-12-01 埃尼奥制药公司 降低干扰素的副作用的方法

Also Published As

Publication number Publication date
JPWO2006033453A1 (ja) 2008-05-15

Similar Documents

Publication Publication Date Title
ES2608483T3 (es) Método mejorado de administración de beta-hidroxi-beta-metilbutirato (HMB)
Patton et al. Development of partial tolerance to the gastrointestinal effects of high doses of recombinant tumor necrosis factor-alpha in rodents.
EP1891089B1 (fr) Inhibiteurs de protease du VHC en combinaison avec des aliments
WO2004073706A1 (fr) Medicament destine a attenuer les effets secondaires dans la therapie combinee interferon ribaverine
WO2008024843A2 (fr) Méthode de thérapie combinatoire pour le traitement d'une infection par le virus de l'hépatite c et compositions pharmaceutiques correspondantes
TW201035099A (en) Therapeutic composition
TW200808308A (en) Novel HCV inhibitor combinations and methods
CN109467566B (zh) 用于治疗和/或预防与肝炎病毒相关的疾病或病症的双二氮杂双环化合物
JP2021119162A (ja) 肝疾患の予防および治療のための薬物の調製におけるトリメタジジンの使用
CN112135625A (zh) 一种预防或治疗covid-19新冠肺炎的药物、食物及其应用
WO2006033453A1 (fr) Amplificateur d'activité pour un agent de type interféron
EP1585524A2 (fr) Utilisation d'endoperoxydes pour le traitement d'infections causees par un flaviviridae, telles que l'hepatite c, la diarrhee virale bovine et le virus de la peste porcine classique
KR20150097256A (ko) C형 간염 바이러스의 게놈 복제의 선택적 저해 활성을 갖는 레스베라트롤 다량체 및 이의 용도
JPH05229940A (ja) 肝再生促進剤
JP5034944B2 (ja) インターフェロン作用物質の活性増強剤
TW201113023A (en) Enhancer of activity of nucleic acid analogue
RU2433827C2 (ru) Профилактический или терапевтический агент против вирусного заболевания
CA2429793C (fr) Ameliorateur de l'effet therapeutique de l'interferon
JP4023863B2 (ja) Ｉｌ−６を含む血清尿酸値低下剤
KR20180105084A (ko) C형 간염 바이러스 질환 치료를 위한 리고세르팁의 신규 용도
WO2012058795A1 (fr) Utilisations d'acides gras insaturés pour inhiber la réplication de virus et/ou l'infection par des virus
RU2721282C2 (ru) Способ лечения рассеянного склероза (варианты)
WO2006093211A1 (fr) Agent antiviral
JP2001247474A (ja) 肝疾患予防及び／又は治療剤
WO2009084732A1 (fr) Agent servant à soulager les effets secondaires néfastes d'une thérapie de combinaison interféron/ribavirine

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KM KP KR KZ LC LK LR LS LT LU LV LY MA MD MG MK MN MW MX MZ NA NG NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SM SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU LV MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2006536439

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 05788141

Country of ref document: EP

Kind code of ref document: A1