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WO2012018145A2 - Agent pour améliorer la qualité de vie - Google Patents

Agent pour améliorer la qualité de vie Download PDF

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WO2012018145A2
WO2012018145A2 PCT/JP2011/068339 JP2011068339W WO2012018145A2 WO 2012018145 A2 WO2012018145 A2 WO 2012018145A2 JP 2011068339 W JP2011068339 W JP 2011068339W WO 2012018145 A2 WO2012018145 A2 WO 2012018145A2
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qol
hepatocellular carcinoma
improving
patients
liver function
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PCT/JP2011/068339
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Japanese (ja)
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WO2012018145A3 (fr
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光彦 川口
義人 畝
研介 後藤
太乙 郭
喜治 角田
栄一 平野
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株式会社日本生物製剤
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    • 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
    • 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
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • 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
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/385—Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/409—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having four such rings, e.g. porphine derivatives, bilirubin, biliverdine
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7012—Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/37—Digestive system
    • A61K35/407—Liver; Hepatocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/48—Reproductive organs
    • A61K35/50—Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
    • 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
    • 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
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to a QOL (Quality of life) improving agent. More specifically, it contains human placenta extract (also called placenta hydrolyzate, placenta hydrolyzate, placenta extract, placenta hydrolyzate, etc.), is inexpensive, and provides QOL for patients with liver cancer (hepatocellular carcinoma).
  • the present invention relates to a QOL improver that can be improved.
  • hepatocellular carcinoma that arises from hepatocytes that are the liver's parenchyma and cholangiocellular carcinoma that arises from the bile duct in the liver, and about 90% of primary liver cancers are hepatocellular carcinoma.
  • 80% to 90% of hepatocellular carcinoma occurs in association with cirrhosis or chronic hepatitis, which is the previous stage.
  • treatment according to the cause (virus, alcohol, non-alcohol, drug, autoimmunity, etc.) is performed (for example, page 11 of Non-Patent Document 1, (See pages 18-19, 26, 36-37, etc.).
  • Hepatocellular carcinoma in which hepatitis / cirrhosis has progressed is a disease with a high recurrence rate, not limited to viral, and metastatic hepatocellular carcinoma is a disease with a poor prognosis.
  • various treatment methods have been tried (see pages 62 to 69 of Non-Patent Document 1).
  • medical local treatment percutaneous ethanol local therapy, Cutaneous microwave coagulation therapy, radiofrequency ablation therapy, etc.
  • TAE hepatic artery embolization therapy
  • hepatic arterial infusion chemotherapy or the like
  • Anti-hepatoma drugs for example, mitoxantrone, miriplatin hydrate, cisplatin, etc.
  • molecular target drug sorafenib trade name: Nexavar, registered trademark
  • Patent Document 1 describes an improvement in QOL of various cancer patients comprising administering a composition containing casein, peptone, RNA, and a serum albumin degradation product. It has not been revealed.
  • the present invention has been made paying attention to the above problems. Its purpose is to reduce the economic burden on hepatocellular carcinoma patients, to suppress or reduce the growth of hepatocellular carcinoma, improve QOL, and consequently to increase the survival rate of hepatocellular carcinoma patients. Intensively studied and found that human placenta extract significantly improves QOL in patients with hepatocellular carcinoma. That is, this invention is providing the QOL improving agent for hepatocellular carcinoma patients which contains a placenta extract as an active ingredient.
  • the gist of the present invention made to solve the above-mentioned problems is a QOL improving agent for hepatocellular carcinoma patients, comprising human placenta extract.
  • the above-mentioned hepatocellular carcinoma patient may be a patient who has been administered a liver function improving agent including an interferon preparation and a nucleic acid related compound preparation.
  • the liver function improving agent include glycyrrhizinate, ursodeoxycholic acid.
  • Adenosine triphosphate flavin adenine dinucleotide, diisopropylamine dichloroacetate, glucuronolactone, glutathione, malotilate, methylmethionine sulfonium chloride, polyemphosphatidylcholine, protoporphyrin salt, branched chain amino acid preparation, liver hydrolyzate, interferon Examples include at least one selected from a preparation and a nucleic acid-related compound preparation. Furthermore, as a human placenta extract, Raeneck (trade name, registered trademark) is preferably used.
  • the present invention also relates to a method for improving QOL, comprising a step of administering an effective amount of human placenta extract to a hepatocellular carcinoma patient, for preparing an agent for improving QOL of a hepatocellular carcinoma patient.
  • a method for improving QOL comprising a step of administering an effective amount of human placenta extract to a hepatocellular carcinoma patient, for preparing an agent for improving QOL of a hepatocellular carcinoma patient.
  • the use of human placenta extract comprising a step of administering an effective amount of human placenta extract to a hepatocellular carcinoma patient, for preparing an agent for improving QOL of a hepatocellular carcinoma patient.
  • placenta extracts eg, Raeneck
  • a liver function improving agent eg, monoammonium glycyrrhizinate
  • the combined administration of the placenta extract and the liver function improving agent enables long-term administration.
  • the cancer cells can be reduced, the subjective symptoms of the patient can be improved, and the QOL can be improved.
  • the placenta extract can also reduce cancer cells by intravenous single continuous administration.
  • placental extract can be used in combination with a liver function improving agent to allow longer-term administration of a liver function improving agent than with a liver function improving agent alone, improving liver function in patients with chronic liver disease.
  • QOL is further improved.
  • it has the feature that side effects caused by these administrations are few. Therefore, according to the present invention, taking into account the low drug price of Raeneck, it has a special effect in the treatment of hepatocellular carcinoma, including end-stage hepatocellular carcinoma.
  • FIG. 1 is a graph showing the inhibitory effect of Raeneck on human hepatocellular carcinoma growth.
  • (a), (b) and (c) show HepG2, HLE and Huh-7 cells, respectively.
  • FIG. 2 is a graph showing the inhibitory effect on the growth of human hepatocellular carcinoma by the combined use of Raennek and monoammonium glycyrrhizinate.
  • (a), (b) and (c) show HepG2, HLE and Huh-7 cells, respectively.
  • ⁇ represents monoammonium glycyrrhizinate alone
  • ⁇ represents monoammonium glycyrrhizinate + 10% raeneck
  • ⁇ represents monoammonium glycyrrhizinate + 20% raeneck.
  • the control (monoammonium glycyrrhizinate 0 ⁇ M) does not contain Raeneck.
  • FIG. 3 is a graph showing that the GOT (AST) value and the GPT value were lowered when Laennec was used in combination with the patients (124 cases) whose GPT value did not fall by the third stage in Example 2. is there.
  • FIG. 4 shows that as a result of combined use of pegylated interferon ⁇ and Laennec in hepatitis C patients who discontinued interferon therapy due to side effects, GOT and GPT values decreased and HCV (human hepatitis C virus) disappeared.
  • shaft is IU / L.
  • FIG. 5 is an abdominal dynamic CT image showing how the ascites of a hepatocellular carcinoma patient disappeared by treatment in Example 4 (part 1).
  • FIG. 6 is an abdominal dynamic CT image showing how the ascites of a hepatocellular carcinoma patient disappeared by treatment in Example 4 (part 2).
  • FIG. 7 is a graph showing the inhibitory effect on the growth of human hepatocellular carcinoma by the combined use of Raeneck and ursodeoxycholic acid.
  • (a), (b) and (c) show HepG2, HLE and Huh-7 cells, respectively.
  • ⁇ represents ursodeoxycholic acid alone
  • ⁇ represents ursodeoxycholic acid + 10% raeneck
  • ⁇ represents ursodeoxycholic acid + 20% raeneck.
  • FIG. 8 is a graph showing the inhibitory effect on the growth of human hepatocellular carcinoma by the combined use of Raeneck and glucuronolactone.
  • (a), (b) and (c) show HepG2, HLE and Huh-7 cells, respectively.
  • ⁇ represents glucuronolactone alone
  • ⁇ represents glucuronolactone + 10% raeneck
  • ⁇ represents glucuronolactone + 20% raeneck.
  • Significant difference tests were performed for glucuronolactone alone and Laennec alone.
  • FIG. 9 is a diagram showing the inhibitory effect on human hepatocellular carcinoma growth by the combined use of Raeneck and glutathione.
  • (a), (b) and (c) show HepG2, HLE and Huh-7 cells, respectively.
  • ⁇ represents glutathione alone
  • ⁇ represents glutathione + 10% raeneck
  • ⁇ represents glutathione + 20% raeneck.
  • FIG. 10 is a graph showing the inhibitory effect on the growth of human hepatocellular carcinoma by the combined use of Laennec and branched amino acids.
  • (a), (b) and (c) show HepG2, HLE and Huh-7 cells, respectively.
  • ⁇ represents a branched amino acid alone
  • ⁇ represents a branched amino acid + 10% raeneck
  • ⁇ represents a branched amino acid + 20% raeneck.
  • FIG. 11 is a graph showing the inhibitory effect on the growth of human hepatocellular carcinoma by the combined use of Raenneck and methylmethioninesulfonium chloride.
  • (a), (b) and (c) show HepG2, HLE and Huh-7 cells, respectively.
  • ⁇ represents methylmethioninesulfonium chloride alone
  • ⁇ represents methylmethioninesulfonium chloride + 10% raeneck
  • ⁇ represents methylmethioninesulfonium chloride + 20% raeneck.
  • the present invention is an agent for improving QOL for patients with hepatocellular carcinoma, comprising human placenta extract.
  • the human placenta extract is not particularly limited in its extraction method, purification method, and treatment method.
  • the human placenta extract is washed with water to remove blood, and if necessary, degreased, Examples thereof include those obtained by removing insoluble components after treatment by conventional methods such as pulverization, freeze-thawing, enzymatic degradation, and acid hydrolysis.
  • the placenta extract is also referred to as placenta decomposition product, placenta hydrolyzate, placenta extract, placenta hydrolyzate and the like.
  • Laennec is a preparation obtained by washing the placenta with water, removing blood, then degreasing with acetone, crushing, enzymatically decomposing with a protease, and further heat acid hydrolysis using hydrochloric acid to remove insoluble components.
  • Laennec contains 112 mg of the above water-soluble substance of human placenta per tube (2 ml), and contains pepsin, lactose and pH adjuster as additives.
  • the pH of Raeneck is 5.5 to 6.5, and the osmotic pressure ratio (ratio to physiological saline) is about 1.
  • Raeneck contains nucleobases in addition to proteins and amino acids, not all the components have been identified.
  • it has been studied for many years which of the contained components is involved in the efficacy effect it has not been elucidated.
  • the effects of human placenta extract-containing products approved as pharmaceuticals are as described above, but it has been revealed that human placenta extract-containing products exhibit various other actions.
  • Raeneck contains hepatocyte growth factor (HGF).
  • HGF hepatocyte growth factor
  • Laennec has been manufactured and sold as a liver function improving agent (intramuscular or subcutaneous administration) for chronic liver diseases since November 1984, but has never been applied to hepatocellular carcinoma.
  • the main reasons are as follows.
  • ⁇ Unlike the drugs listed above, which have the same efficacy and effect as Laenneq (improved liver function for chronic liver disease), the mechanism for improving liver function has not been elucidated;
  • ⁇ There is no scientific basis (experimental data) for administering Raennec to patients with hepatocellular carcinoma; -Of the drugs listed above that have the same efficacy and effect as Laenneq (improved liver function for chronic liver disease), only a part of those drugs that have been studied for anti-hepatocellular carcinoma activity (ie, adenosine) Only sodium triphosphate, flavin adenine dinucleotide, monosodium glycyrrhizinate, ursodeoxycholic acid, etc.); ⁇ In addition, there are no reports
  • the improvement of QOL means that the quality of life of a patient who has been lowered due to hepatocellular carcinoma is improved and then maintained to bring it closer to the normal human life.
  • long-term treatment with anticancer drugs may conversely shorten the life of the patient, and even if the cancer is not completely cured, the life can be prolonged. Based on the idea that it is essential to have a comfortable life.
  • Examples of QOL of patients who have decreased due to hepatocellular carcinoma include loss of appetite, weight loss, fatigue, general malaise, slight fever, abdominal distension, abdominal pain, ascites, jaundice and the like.
  • the QOL improving agent of this invention contains a placenta extract
  • content in a formulation will not be specifically limited, It can be set as a suitable quantity.
  • conventional auxiliaries such as stabilizers, antioxidants, pH adjusters and soothing agents can be added.
  • the dose of the placental extract to the hepatocellular carcinoma patient can be appropriately selected depending on the degree of disease, age, weight, etc. of the patient. (Containing 112 mg of placenta-derived component per ampoule) is administered once or divided into several times.
  • As an administration method subcutaneous administration and intramuscular administration for which Raeneck is approved, and intravenous administration (use outside application) are also possible.
  • the QOL improving agent of the present invention uses a liver function improving agent together with a placenta extract, they act synergistically to produce more excellent effects. That is, it is preferable that a hepatocellular carcinoma patient is administered a liver function improving agent together with the QOL improving agent of the present invention.
  • the liver function improving agent means a drug that can suppress hepatitis, improve liver function, and suppress progression to liver cirrhosis or liver cancer regardless of disease-specific drugs and non-specific drugs.
  • examples of such liver function improving agents include the following examples, including interferon preparations and nucleic acid related compound preparations which are disease-specific drugs.
  • Glycyrrhizinate (monoammonium salt, monosodium salt): for example, strong minophagen P (intravenous injection) (trade name), strong neominophagen C (trade name) Adenosine triphosphate (sodium salt): For example, ATP Note 1 (trade name) Flavin adenine dinucleotide: eg Adelabin 9 Note (trade name) Ursodeoxycholic acid: For example, Urso tablet (trade name) Diisopropylamine dichloroacetate: for example Ribaol tablets (trade name) Glucuronolactone: Gronsan Injection (trade name), for example Glutathione: For example, Tachion Note (trade name) Malotilate: For example, Kandec Tablet (trade name) Methylmethionine sulfonium chloride: For example, Cavedin U Kowa (trade name) Polyenphosphatidylcholine: For example, Blobin capsule (trade
  • liver function improving agent glycyrrhizinate, ursodeoxycholic acid, branched chain amino acid preparation, glucuronolactone, glutathione, and methylmethionine sulfonium chloride are preferable, and glycyrrhizinate and ursodeoxycholic acid are particularly preferable.
  • Example 1 We investigated the growth inhibition effect of human hepatocarcinoma cells in vitro by the combined use of Raenneck and monoammonium glycyrrhizinate. [Materials and experimental methods] Reagent : Laeneck was used as the placenta extract. MTT assay was purchased from Nacalai.
  • HepG2 liver cancer cell lines, differentiated, obtained from RIKEN
  • HLE liver cancer cell lines, undifferentiated, obtained from JCRB (Japanese Collection of Research Bioresources) ) 10% serum-containing DMEM medium, Huh-7 (Hepatoma cell line, well-differentiated type, obtained from Tohoku University Research Institute for Aging) were each cultured in RPMI medium containing 10% serum.
  • Example 2 This example shows that QOL of hepatitis patients affected by B virus, C virus, non-B non-C virus, and other causes is improved by administration of Raeneck. In the case of viral hepatitis, the goal is to eliminate the virus and lower the GPT value.
  • liver function improving agent combination of ursodeoxycholic acid and monoammonium glycyrrhizinate
  • the relationship between changes in GOT and GPT values and QOL improvement was examined.
  • the following knowledge was obtained.
  • Regimens for administration of liver function improving agents The total number of hepatitis patients (759 cases) treated for liver function improving agent administration, etc. is as shown in Table 1, but the patient's subjective findings and other objective findings (blood data, blood life Based on changes in chemical data, etc., the regimen for administration of liver function improving agents was as follows in principle.
  • First stage Ursodeoxycholic acid (600 mg / day) orally administered
  • Second stage Ursodeoxycholic acid and monoammonium glycyrrhizinate (40 ml to 60 ml three times a week) intravenously
  • Third stage Ursodeoxycholic Increase the amount of monoammonium glycyrrhizinate used in combination with acid (60 ml to 100 ml 3 times a week)
  • ii) Clinical effects
  • Example 3 A man in his 50s who suffered from hepatitis C (genotype 2a), compensatory cirrhosis, and diffuse hepatocellular carcinoma. He was sentenced to one month of life in a hospital in Hiroshima Prefecture on April 9, 2007. I visited the hospital. He had subjective symptoms such as general malaise and loss of appetite, and his face was browned. April 20, 2007: With the consent of the patient, Laennek (one ampoule once every other day in the muscles) and monoammonium glycyrrhizinate (every other day, 3 ampoules intravenously) were started. UFT (Tegafur uracil, 2 tablets daily) was also prescribed. The results are shown over time.
  • Example 4 The case was a man in his 50s who had a blood transfusion due to a traffic accident when he was 25 years old. I was working without any particular problems.
  • Example 7 We investigated the growth inhibitory effect of human hepatocarcinoma cells in vitro by the combined use of Raennec and glucuronolactone. The determination of the presence of the material, the experimental method, and the combined effect is the same as in Example 5. The test results are shown in FIG. As shown in FIG.
  • Example 7 We investigated the growth inhibitory effect of human hepatocarcinoma cells in vitro by the combined use of Laennec and glutathione. The determination of the presence of the material, the experimental method, and the combined effect is the same as in Example 5. The test results are shown in FIG. As shown in FIG. 9, when glutathione was used in combination with 10% Laennec, HepG2 and Huh-7 did not show a significant growth-inhibiting effect on cancer cells, but markedly suppressed against HLE.
  • Example 8 We investigated the growth inhibitory effect of human hepatoma cells in vitro by the combined use of Laennec and branched amino acids. The determination of the presence of the material, the experimental method, and the combined effect is the same as in Example 5.
  • the test results are shown in FIG.
  • FIG. 10 when 10% Laennec was used in combination with a branched amino acid, HepG2 and Huh-7 did not show a significant growth inhibitory effect on cancer cells, but were prominent for HLE.
  • Example 9 We investigated the growth-inhibitory effect of human hepatoma cells in vitro by the combined use of Raennec and methylmethioninesulfonium chloride. The determination of the presence of the material, the experimental method, and the combined effect is the same as in Example 5. The test results are shown in FIG. As shown in FIG. 11, when 10% Laeneck was used in combination with methylmethioninesulfonium chloride, HepG2 and Huh-7 did not show a significant growth inhibitory effect on cancer cells. A remarkable inhibitory effect was shown (see ⁇ in FIG. 11B).
  • the QOL improving agent of the present invention hepatoma cells can be reduced, patient's subjective symptoms can be improved, and QOL can be improved, so that it is useful in the treatment of hepatocellular carcinoma including end-stage hepatocellular carcinoma.
  • the QOL improving agent of the present invention when used in combination with a liver function improving agent, can significantly suppress the growth of hepatocellular carcinoma due to their synergistic effect, and thus is useful for the treatment of hepatocellular carcinoma.

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  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physiology (AREA)
  • Pregnancy & Childbirth (AREA)
  • Reproductive Health (AREA)
  • Nutrition Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Steroid Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un agent pour améliorer la qualité de vie de patients atteints d'un carcinome hépatocellulaire. Cet agent est caractérisé en ce qu'il contient un extrait de placenta humain, et qu'il est de préférence utilisé simultanément avec un agent d'amélioration de la fonction hépatique (par exemple, un glycyrrhizinate). Cet agent permet de faire rétrécir les cellules d'hépatome, de soulager les symptômes subjectifs des patients et d'améliorer leur qualité de vie, et ainsi, cet agent est particulièrement efficace pour traiter un carcinome hépatocellulaire, y compris un carcinome hépatocellulaire au stade terminal.
PCT/JP2011/068339 2010-08-05 2011-08-04 Agent pour améliorer la qualité de vie WO2012018145A2 (fr)

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JP2010-176441 2010-08-05
JP2010176441 2010-08-05

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WO2012018145A2 true WO2012018145A2 (fr) 2012-02-09
WO2012018145A3 WO2012018145A3 (fr) 2012-03-29

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2015526469A (ja) * 2012-08-20 2015-09-10 ボリス, マルコシアンMarkosian, Boris 癌に対する胎盤ワクチン接種療法
WO2022191309A1 (fr) * 2021-03-12 2022-09-15 ドクタープロラボジャパン株式会社 Procédé d'utilisation d'un extrait de placenta
EP4512395A1 (fr) * 2023-08-21 2025-02-26 Bio Even Composition comprenant de la flavine adenine dinucleotide (fad), l-gsh, de l'acide atp et de l'acide myristique, seul ou avec un medicament

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101108001B (zh) * 2002-12-26 2011-12-14 味之素株式会社 保健功能食品

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2015526469A (ja) * 2012-08-20 2015-09-10 ボリス, マルコシアンMarkosian, Boris 癌に対する胎盤ワクチン接種療法
WO2022191309A1 (fr) * 2021-03-12 2022-09-15 ドクタープロラボジャパン株式会社 Procédé d'utilisation d'un extrait de placenta
JP2022140106A (ja) * 2021-03-12 2022-09-26 国立大学法人九州大学 プラセンタ抽出物の使用方法
EP4512395A1 (fr) * 2023-08-21 2025-02-26 Bio Even Composition comprenant de la flavine adenine dinucleotide (fad), l-gsh, de l'acide atp et de l'acide myristique, seul ou avec un medicament

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