WO2016175042A1 - Agent médicinal contenant un composé de magnésium en tant qu'ingrédient actif - Google Patents

Agent médicinal contenant un composé de magnésium en tant qu'ingrédient actif Download PDF

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Publication number
WO2016175042A1
WO2016175042A1 PCT/JP2016/062053 JP2016062053W WO2016175042A1 WO 2016175042 A1 WO2016175042 A1 WO 2016175042A1 JP 2016062053 W JP2016062053 W JP 2016062053W WO 2016175042 A1 WO2016175042 A1 WO 2016175042A1
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Prior art keywords
magnesium
platinum
tablet
magnesium oxide
compound
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PCT/JP2016/062053
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English (en)
Japanese (ja)
Inventor
勇哉 吉村
孝輔 藤崎
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協和化学工業株式会社
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Priority claimed from JP2015093307A external-priority patent/JP2018104291A/ja
Priority claimed from JP2015094833A external-priority patent/JP2018104292A/ja
Application filed by 協和化学工業株式会社 filed Critical 協和化学工業株式会社
Publication of WO2016175042A1 publication Critical patent/WO2016175042A1/fr

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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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/243—Platinum; Compounds thereof
    • 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
    • A61K31/28—Compounds containing heavy metals
    • A61K31/282—Platinum compounds
    • 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
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A61K33/08—Oxides; Hydroxides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A61K33/12—Magnesium silicate
    • 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

Definitions

  • the present invention relates to a pharmaceutical preparation containing a specific magnesium compound that reduces renal damage caused by a drug. More specifically, specific magnesium as an active ingredient for maintaining renal function without reducing renal function in patients with platinum compound-induced renal damage expressed in patients receiving platinum-containing chemical preparations in anticipation of anticancer effects
  • the present invention relates to a pharmaceutical preparation containing a compound.
  • platinum compound responsive malignant tumors (testicular tumor, bladder cancer, renal pelvis / ureter tumor, prostate cancer, ovarian cancer, head and neck cancer, non-small cell lung cancer, esophageal cancer, cervical cancer, neuroblastoma, gastric cancer, small Platinum-containing chemicals are often prescribed for patients with (cell lung cancer, osteosarcoma, germ cell tumor, malignant pleural mesothelioma, biliary tract cancer).
  • This platinum-containing chemical preparation has a strong anti-cancer action against platinum compound-responsive malignant tumors and is an indispensable anti-cancer agent for treatment, but it often shows severe kidney damage as a side effect. Renal function decline is common in patients undergoing treatment. Decreased renal function varies from mild to severe, but kidney function deteriorates irreversibly and often causes chronic renal failure. The quality of life (QOL) is greatly reduced. In particular, when platinum-containing chemicals are administered repeatedly over a long period of time, the cumulative toxicity of these drugs necessitates dose reductions and changes to other drugs depending on the patients who have developed renal impairment. It may cause a decrease in Therefore, deterioration of kidney function is considered as a serious side effect that may lead to shortening of life span.
  • therapies that promote the excretion of platinum compounds from the kidney include the use of diuretics and hydration therapy in which water is applied by infusion before and after administration of platinum-containing chemicals.
  • a short hydration method with reduced time has also been devised, but it is not enough to prevent renal function decline, and patients are forced to be restrained for a long time by medical practice, and there is a need for alternative measures to reduce kidney damage. It was done.
  • the present inventor prevents or reduces renal damage caused by a platinum-containing chemical preparation by orally administering to a patient, reduces the burden on the patient, eases the time restriction of receiving platinum compound excretion therapy such as hydration, and the like.
  • the development of a formulation that improves the quality of life was promoted.
  • oral administration of specific magnesium compounds can prevent or reduce the above-mentioned renal damage caused by platinum compounds, ease the burden on patients and time constraints, and improve the acceptability of treatment with anticancer agents.
  • This pharmaceutical preparation of the present invention can reduce platinum compound-induced renal injury by the action of a specific magnesium compound, can be released from the time restriction of platinum compound excretion therapy of patients in order to reduce renal damage, For example, since it can be taken in the form of tablets or granules, it has been found that the burden on patients can be reduced and the acceptability of anticancer drug treatment can be improved.
  • the present invention has been achieved based on the above findings, and according to the present invention, the following pharmaceutical preparations and methods for using the same are provided.
  • the tablet or granule according to the above (1) which further contains a binder, a disintegrant and a lubricant as additive components.
  • the tablet or granule according to (1) wherein the disintegration time measured in water does not exceed 30 seconds.
  • the platinum-containing chemical preparation includes cisplatin (cis-diamine dichloroplatinum), oxaliplatin (cis-1,2-cyclohexanediamine-oxalate platinum), carboplatin (cis-diamine-1,1-cyclobutanedicarboxalate).
  • the tablet or granule according to the above (1) comprising as an active ingredient at least one selected from the group consisting of platinum) and nedaplatin (cis-diamine glycolate platinum). (7) Orally administering a tablet or granule containing 80% by mass or more of at least one magnesium compound selected from the group consisting of magnesium oxide, magnesium hydroxide, magnesium silicate and magnesium citrate A method for preventing or treating renal damage caused by a platinum-containing chemical preparation.
  • the tablet or granule of the present invention has an effect of suppressing or reducing platinum compound-induced renal damage by taking a magnesium compound before or during treatment by administration of a platinum-containing chemical preparation as an anticancer agent.
  • the ability to relieve the patient from the time-constrained platinum compound excretion therapy to suppress or alleviate kidney damage, significantly reduce the burden on patients because it can be taken in an oral form, and improve the acceptability of anticancer drug treatment Has the advantage of being able to.
  • the tablet or granule of the present invention is excellent in disintegration, and has an advantage that the disintegration time (in water) does not exceed 30 seconds, and preferably 20 seconds or less.
  • the tablet or granule containing the magnesium compound of the present invention can be easily taken orally and can reduce the platinum compound-induced renal damage caused by administering the platinum compound before treatment. As a result, it was found that the burden on the platinum compound can be reduced and the acceptability of the anticancer drug treatment can be improved.
  • the tablet or granule of the present invention contains magnesium oxide, magnesium hydroxide, magnesium silicate, magnesium citrate, or a mixture of two or more thereof as active ingredients.
  • magnesium oxide, magnesium hydroxide, or magnesium silicate is preferable, and magnesium oxide is particularly preferable.
  • the content of the magnesium compound contained in the tablet or granule of the present invention is 80% by mass or more, preferably 80 to 95% by mass, particularly preferably 83 to 92% by mass.
  • the average secondary particle diameter of the magnesium compound for formulating a tablet or granule will be described.
  • the average secondary particle diameter is preferably 0.5 to 10 ⁇ m, particularly preferably 1.0 to 7.0 ⁇ m. It is.
  • the average secondary particle diameter is preferably 0.5 to 20 ⁇ m, particularly preferably 1.0 to 15.0 ⁇ m.
  • the average secondary particle size is preferably 0.5 to 20 ⁇ m, particularly preferably 1.0 to 15.0 ⁇ m.
  • the average secondary particle size is preferably 10.0 to 200.0 ⁇ m, particularly preferably 50.0 to 150.0 ⁇ m.
  • the tablet may be tableted or granulated according to an ordinary method using the predetermined ratio of the magnesium compound described above.
  • additive components such as a binder, a disintegrant, and a lubricant may be mixed with the magnesium compound particles, and the resulting mixture may be formulated.
  • Binders include sodium carboxymethylcellulose, low substituted hydroxypropylcellulose, corn starch, potato starch, D-mannitol and crystalline cellulose, preferably corn starch, D-mannitol and crystalline cellulose, particularly preferably D-mannitol. And crystalline cellulose.
  • the content of the binder is 1 to 10% by mass, preferably 1.2 to 5% by mass, particularly preferably 1.5 to 3% by mass.
  • Disintegrants include croscarmellose sodium, carboxymethylcellulose calcium, carmellose, carboxystarch sodium, low-substituted hydroxypropylcellulose and insoluble polyvinylpyrrolidone, preferably croscarmellose sodium, carboxystarch sodium and insoluble polyvinylpyrrolidone, particularly preferably cross Carmellose sodium and insoluble polyvinylpyrrolidone.
  • the content of the disintegrant is 1 to 20% by mass, preferably 5 to 20% by mass, particularly preferably 5 to 10% by mass.
  • the lubricant examples include calcium stearate and magnesium stearate, preferably calcium stearate.
  • the content of the lubricant is 0.5 to 2% by mass, preferably 0.7 to 1.8% by mass, and particularly preferably 0.8 to 1.6% by mass.
  • the daily intake per person will be described.
  • the lower limit is 0.5 g, preferably 1 g, and the upper limit is 6 g, preferably 5 g. .
  • the upper limit is 8 g, preferably 7 g.
  • the lower limit is 5 g, preferably 10 g
  • the upper limit is 75 g, preferably 60 g.
  • the lower limit is 2 g, preferably 4.5 g
  • the upper limit is 25 g, preferably 20 g. It should be understood that these lower and upper limit values are general amounts and will vary depending on the extent of renal injury and the patient's condition with the platinum-containing chemical.
  • the medicament of the present invention contains a magnesium compound as an active ingredient.
  • the magnesium compound as an active ingredient is 10 mg, preferably 30 mg, more preferably 50 mg, more preferably 650 mg, preferably 600 mg as the upper limit, in terms of magnesium metal per dose. More preferably, it is desirable to take 500 mg.
  • the magnesium concentration in the blood after administration of the pharmaceutical composition of the present invention is 0.75 mmol / L, preferably 0.8 mmol / L, more preferably 0.9 mmol / L, and 2 as the upper limit. It is preferable to administer such that it is maintained at 3 mmol / L, preferably 2.2 mmol / L, more preferably 2.0 mmol / L.
  • the amount of magnesium described above is the total amount maintained in the blood when used for a single administration, and may be administered as a sustained release preparation that can be absorbed slowly or divided into 2 to 3 portions. it can.
  • the magnesium concentration in the blood is 0.75 mmol / L as a lower limit, preferably 0.8 mmol / L, more preferably 0.9 mmol / L, 2.3 mmol / L as an upper limit, If it can be preferably maintained at 2.2 mmol / L, more preferably 2.0 mmol / L, the amount of medicine to be administered at each time does not need to be equal, and may be appropriately changed.
  • the medicament of the present invention can be continuously administered 1 to 3 days before administration of the platinum-containing chemical preparation, more preferably from one week before, and can also be continuously administered after administration of the platinum-containing chemical preparation. .
  • Platinum-containing chemical preparations as anticancer agents are usually mixed with physiological saline or glucose-saline and administered by intravenous infusion.
  • the usage and dose of the platinum-containing chemical preparation may be determined depending on the type of preparation, the type of tumor, the condition of the patient, the presence or absence of concomitant use with other tumor agents, and the dose and frequency are not in a certain range. Specifically, it is prescribed in the Japanese Pharmacopoeia.
  • the lower limit is 10 mg / m 2 once a day (the body surface area, hereinafter the unit of “m 2 ” indicates the body surface area), preferably
  • the upper limit is 15 mg / m 2
  • the upper limit is 100 mg / m 2 , preferably 90 mg / m 2 .
  • it is 80 to 150 mg / m 2 once a day
  • carboplatin 300 to 400 mg / m 2 once a day
  • nedaplatin 80 to 100 mg / m 2 once a day. It is.
  • Example 1 (I) Examination method Animal test rats were allowed to take magnesium oxide as a magnesium compound, and the serum magnesium concentration at a predetermined time point from 5 minutes to 72 hours was measured. (Ii) Magnesium compound used This evaluation relates to a preparation containing magnesium oxide as the magnesium compound. A magnesium oxide preparation in the form of a tablet containing 500 mg of magnesium oxide per tablet was used as the magnesium oxide preparation, and a suspension-disintegrated solution was used for administration to rats. The magnesium oxide used consists of magnesium oxide particles having an average secondary particle size of 0.5 to 10 ⁇ m.
  • Example 1 In order to clarify the migration of magnesium from the magnesium compound into the blood, rats were given a magnesium oxide preparation at a dose of 200 mg / kg or 400 mg / kg, and the serum magnesium concentration was measured. The total dose of each test group was constant (5 mL / kg). Blood was collected every predetermined time, and the magnesium concentration (mmol / L) in serum was evaluated. Table 1 shows the serum magnesium concentration (mmol / L) of rats administered orally with magnesium oxide.
  • magnesium oxide as a magnesium compound, the magnesium concentration in the blood can be increased, the blood concentration can be controlled in relation to the dose, and if overdose, the administration of the magnesium can be stopped promptly It was confirmed that it was excreted.
  • Example 2 (I) Testing method Magnesium oxide was administered as a magnesium compound to the animal test rats, and the amount of magnesium in urine and feces excreted by 72 hours was measured.
  • Magnesium oxide particles used The present evaluation relates to a preparation containing magnesium oxide as a magnesium compound.
  • a magnesium oxide preparation in the form of a tablet containing 500 mg of magnesium oxide per tablet was used as the magnesium oxide preparation, and a suspension-disintegrated solution was used for administration to rats.
  • the magnesium oxide used consists of magnesium oxide particles having an average secondary particle size of 0.5 to 10 ⁇ m.
  • Example 2 In order to clarify the migration rate of magnesium from the magnesium compound, the magnesium oxide preparation was administered to rats at 400 mg / kg as the amount of magnesium oxide, and the amount of magnesium in urine and feces excreted by 72 hours was measured. The total liquid dose was constant (5 mL / kg). Urine and feces were collected every 24 hours, and after measuring the amount of magnesium in each sample, the average values of control urine and fecal magnesium were subtracted, respectively, and the ratio to the dose of magnesium was calculated and evaluated. Table 2 shows the ratio of magnesium excreted in urine and feces of rats administered orally with magnesium oxide to the dose. Each data was an average value ⁇ standard deviation. By taking magnesium oxide as a magnesium compound, about 15% of magnesium is transferred into the blood, and the transfer into blood from Example 1 depends on the dose, so the blood correlated with the dose. It was confirmed that concentration control was possible.
  • Example 3 (I) Examination Method Rats for animal test were given magnesium oxide as a magnesium compound repeatedly once a day for 7 days, and the serum magnesium concentration was measured 2-3 hours after administration on each day.
  • Magnesium oxide particles used The present evaluation relates to a preparation containing magnesium oxide as a magnesium compound. A magnesium oxide preparation in the form of a tablet containing 500 mg of magnesium oxide per tablet was used as the magnesium oxide preparation, and a suspension-disintegrated solution was used for administration to rats.
  • the magnesium oxide used consists of magnesium oxide particles having an average secondary particle size of 0.5 to 10 ⁇ m.
  • Example 3 In order to clarify the retention in blood after repeated administration of magnesium oxide particles, the magnesium oxide preparation was administered to rats at a dose of 200 mg / kg or 400 mg / kg as the amount of magnesium oxide once a day. It was measured. The dose of each dose was fixed (5 mL / kg). Serum was taken once a day for 7 days, blood was collected every 2-3 hours after administration on each administration day, and the magnesium concentration (mmol / L) in the serum for 7 days was evaluated. Table 3 below shows the serum magnesium concentration (mmol / L) of rats subjected to repeated oral administration of magnesium oxide for 7 days. It was confirmed that by taking magnesium oxide as a magnesium compound, the serum magnesium concentration can be increased, the serum magnesium concentration can be maintained continuously by repeated administration for 7 days, and the blood concentration can be controlled in relation to the dose. .
  • Example 4 (I) Test method Based on the Japanese Pharmacopoeia dissolution test method, the amount of magnesium eluted in the first dissolution test solution was measured, and the dissolution rate was calculated from the sample.
  • the dissolution test was carried out using a dissolution tester (NTR-8000AC; Toyama Sangyo Co., Ltd.) and the first dissolution solution (pH 1.2) at a paddle method of 50 rpm.
  • the test preparation is supplied to a dissolution test solution, and a part of the test solution is collected at predetermined time intervals, and the collected test solution is appropriately diluted and measured by an atomic absorption photometry (atomic absorption photometer AA-6300; Shimadzu Corporation). Quantified.
  • magnesium oxide magnesium oxide, magnesium hydroxide, magnesium silicate, or magnesium citrate particles were used. Further, as a preparation containing a magnesium compound, a magnesium oxide preparation in the form of a tablet containing 500 mg of magnesium oxide particles per tablet was used as a magnesium oxide preparation.
  • Example 4 In order to clarify the elution property of magnesium from the magnesium compound, a Japanese Pharmacopoeia elution test was conducted, and the magnesium concentration eluted in the elution test solution was measured. The magnesium concentration was converted with respect to the sample amount, and the elution rate of the magnesium compound was calculated. The elution rate (%) of the magnesium compound is shown in Table 4 below. It was suggested that by taking magnesium compound particles, magnesium is eluted in the stomach and the concentration of magnesium in the blood can be increased.
  • Example 5 Test method Magnesium oxide-containing food was given to 8-week-old SD male rats. This diet contained 400 mg / kg of magnesium oxide as a daily dose. On the other hand, cisplatin 7.0 mg / kg was intraperitoneally administered and blood was collected to evaluate renal function. The diet was given and acclimatized from one week before cisplatin administration and continued from the end of cisplatin administration until the end of the study. The time of blood collection was before cisplatin administration and 1, 3, 5, 7, 14, 21, and 28 days after administration, and renal function evaluation items were creatinine (Cre) and blood urea nitrogen (BUN). (Ii) Magnesium oxide used In this evaluation, a feed in which magnesium oxide sold as a food additive was kneaded into an animal feed was used, and a feed corresponding to the daily feed amount was given as a feed.
  • Example 5 In Example 5, renal function was evaluated in the same manner as in Example 5 except that a normal diet containing no magnesium oxide was given. The results of Example 5 and Reference Example 1 are collectively shown in Tables 5 and 6 below.
  • Example 5 Comparison of Evaluation between Example 5 and Reference Example 1
  • Example 5 it was shown that an increase in creatinine and an increase in blood urea nitrogen were clearly suppressed, and renal damage caused by cisplatin was reduced.
  • magnesium since magnesium was rapidly excreted even when it moved into the blood, it did not accumulate, indicating the effectiveness of a diet containing MgO.
  • Reference Example 1 creatinine and blood urea nitrogen were remarkably increased with a decrease in renal function, and an increase in blood Mg level was observed due to the migration of magnesium leaked from cells due to cell damage caused by cisplatin into the blood.
  • Example 6 Test method Eight weeks old SD male rats were usually fed. Rats were orally administered 200 mg / kg of magnesium oxide. On the other hand, cisplatin 7.0 mg / kg was intraperitoneally administered and blood was collected to evaluate renal function. Magnesium oxide to be administered was suspended in 0.5% CMC-Na in 500 mg magnesium oxide tablet to 40 mg / mL, and then 5 mL / kg was orally administered to rats once a day. Oral administration of magnesium oxide was continued from 3 days before cisplatin administration to 1 day after administration. The time of blood collection was before cisplatin administration and 1, 3, 5, 7, 14, 21, and 28 days after administration, and renal function evaluation items were creatinine (Cre) and blood urea nitrogen (BUN).
  • Re creatinine
  • BUN blood urea nitrogen
  • Magnesium oxide used in this evaluation a magnesium oxide preparation in the form of a tablet containing 500 mg of magnesium oxide per tablet was used as the magnesium oxide preparation, and the suspension was disintegrated for administration to rats. .
  • the magnesium oxide used consists of magnesium oxide particles having an average secondary particle size of 0.5 to 10 ⁇ m.
  • Example 6 In Example 6, renal function was evaluated in the same manner as in Example 6 except that magnesium oxide was not orally administered. The results of Example 6 and Reference Example 2 are collectively shown in Tables 7 and 8 below.
  • Example 6 As compared with Reference Example 2, an increase in creatinine and an increase in blood urea nitrogen were suppressed, and it was shown that renal damage caused by cisplatin was reduced. In addition, no increase in blood magnesium level due to oral administration of magnesium oxide was observed, indicating the effectiveness of oral administration of magnesium oxide. On the other hand, in Reference Example 2, creatinine and blood urea nitrogen significantly increased with a decrease in renal function.
  • the pharmaceutical preparation of the present invention can prevent or reduce renal damage caused by drugs, can greatly reduce the burden on patients treated with anticancer drugs, and improve the quality of life.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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Abstract

La présente invention concerne un comprimé ou un granulé à administration par voie orale permettant de prévenir ou de traiter des troubles rénaux induits par un agent chimique contenant du platine, lequel comprimé ou granulé contient 80 % en poids ou plus d'au moins un composé de magnésium choisi dans le groupe constitué d'un oxyde de magnésium, d'un hydroxyde de magnésium, d'un silicate de magnésium et d'un citrate de magnésium.
PCT/JP2016/062053 2015-04-30 2016-04-15 Agent médicinal contenant un composé de magnésium en tant qu'ingrédient actif WO2016175042A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP2015093307A JP2018104291A (ja) 2015-04-30 2015-04-30 マグネシウム化合物を有効成分として含有することを特徴とする医薬組成物
JP2015-093307 2015-04-30
JP2015094833A JP2018104292A (ja) 2015-05-07 2015-05-07 マグネシウム化合物を有効成分とする医薬組成物
JP2015-094833 2015-05-07

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WO2016175042A1 true WO2016175042A1 (fr) 2016-11-03

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000001428A (ja) * 1998-04-16 2000-01-07 Nippon Shinyaku Co Ltd 錠剤及び製造法
JP2004352633A (ja) * 2003-05-28 2004-12-16 Kowa Co 酸化マグネシウム錠剤
JP2006131555A (ja) * 2004-11-05 2006-05-25 Dai Ichi Seiyaku Co Ltd 制酸剤組成物
JP2006249052A (ja) * 2005-03-14 2006-09-21 Kyowa Hakko Kogyo Co Ltd 酸化マグネシウム粒子
JP2007525476A (ja) * 2003-07-09 2007-09-06 ブレーントリー ラボラトリーズ インコーポレーティッド 緩下薬を用いた過敏性腸症候群の治療法
WO2011030659A1 (fr) * 2009-09-08 2011-03-17 協和化学工業株式会社 Comprimé antiacide et laxatif

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000001428A (ja) * 1998-04-16 2000-01-07 Nippon Shinyaku Co Ltd 錠剤及び製造法
JP2004352633A (ja) * 2003-05-28 2004-12-16 Kowa Co 酸化マグネシウム錠剤
JP2007525476A (ja) * 2003-07-09 2007-09-06 ブレーントリー ラボラトリーズ インコーポレーティッド 緩下薬を用いた過敏性腸症候群の治療法
JP2006131555A (ja) * 2004-11-05 2006-05-25 Dai Ichi Seiyaku Co Ltd 制酸剤組成物
JP2006249052A (ja) * 2005-03-14 2006-09-21 Kyowa Hakko Kogyo Co Ltd 酸化マグネシウム粒子
WO2011030659A1 (fr) * 2009-09-08 2011-03-17 協和化学工業株式会社 Comprimé antiacide et laxatif

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KIDERA,Y. ET AL.: "Risk Factors for Cisplatin-Induced Nephrotoxicity and Potential of Magnesium Supplementation for Renal Protection", PLOS ONE, vol. 9, no. 7, e101902, 2014, pages 1 - 10, XP055327052 *
YOSHIKI ARITA ET AL.: "Keiko Magnesium-zai no Renjitsu Toyo ni yoru Cisplatin Toyoji no Jin Hogo Koka no Kento", ANNUAL MEETING OF JAPANESE SOCIETY OF PHARMACEUTICAL HEALTH CARE AND SCIENCES KOEN YOSHISHU, vol. 24, 2014, pages 342 *

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