[go: up one dir, main page]

WO2015045037A1 - Préparation en capsule - Google Patents

Préparation en capsule Download PDF

Info

Publication number
WO2015045037A1
WO2015045037A1 PCT/JP2013/075926 JP2013075926W WO2015045037A1 WO 2015045037 A1 WO2015045037 A1 WO 2015045037A1 JP 2013075926 W JP2013075926 W JP 2013075926W WO 2015045037 A1 WO2015045037 A1 WO 2015045037A1
Authority
WO
WIPO (PCT)
Prior art keywords
tamibarotene
capsule
propylene glycol
mass
capsule preparation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2013/075926
Other languages
English (en)
Japanese (ja)
Inventor
秋山　英郎
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
TMRC Co Ltd
Original Assignee
TMRC Co Ltd
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 TMRC Co Ltd filed Critical TMRC Co Ltd
Priority to PCT/JP2013/075926 priority Critical patent/WO2015045037A1/fr
Publication of WO2015045037A1 publication Critical patent/WO2015045037A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia

Definitions

  • the present invention relates to a capsule preparation containing tamibarotene.
  • Retinoic acid is a substance having physiological functions that are extremely important for life-supporting action, such as differentiating developing immature cells into mature cells having a specific function, or promoting cell proliferation. It is. Clinically, retinoic acid has been found useful for the treatment of vitamin A deficiency, epithelial keratosis, leukemia and certain cancers. Drugs using such physiological functions of retinoids have been developed. One of these is tamibarotene, which is known as a therapeutic agent for cancers such as leukemia (for example, JP-A-7-17584).
  • Capsule preparations are filled with glycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, propylene glycol fatty acid ester, ethylene glycol fatty acid ester, decaglycerin fatty acid ester, etc. in order to dissolve a poorly soluble drug in water and fill the capsule. It has been proposed to use it as a liquid base (for example, JP-A-5-25037). Tamibarotene is also known to be excellent in stability and easy to take by making into a capsule formulation. For example, WO 2008/056073 pamphlet contains propylene glycol monooleate as a filling liquid. A capsule formulation based on the above is disclosed.
  • an object of the present invention is to provide a capsule preparation containing tamibarotene and having excellent stability over time.
  • the present invention is as follows.
  • [1] A capsule preparation in which a filling liquid containing tamibarotene and propylene glycol monocaprylate is coated with a coating component.
  • [2] The capsule preparation according to [1], wherein the filling liquid contains 0.1% by mass to 10.0% by mass of tamibarotene.
  • [3] The capsule formulation according to [1], wherein the filling liquid contains 0.1% by mass to 8.0% by mass of tamibarotene.
  • [5] The capsule preparation according to any one of [1] to [4] for the treatment of blood cancer or solid cancer.
  • the capsule formulation of the present invention is a capsule formulation in which a filling liquid containing tamibarotene and propylene glycol monocaprylate is coated with a coating component.
  • a filling liquid containing tamibarotene and propylene glycol monocaprylate is coated with a coating component.
  • the term “process” is not limited to an independent process, and is included in the term if the intended purpose of the process is achieved even when it cannot be clearly distinguished from other processes. .
  • a numerical range indicated by using “to” indicates a range including the numerical values described before and after that as the minimum value and the maximum value, respectively.
  • the amount of each component in the composition is the total amount of the plurality of substances present in the composition unless there is a specific indication when there are a plurality of substances corresponding to each component in the composition. means. The present invention will be described below.
  • Tamibarotene which is an active ingredient of the present invention is 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl) carbamoyl] benzoic acid.
  • tamibarotene either a crystal obtained by normal production or a crystalline powder can be used.
  • the method for producing tamibarotene include the methods described in Japanese Patent No. 3001632, Japanese Patent Laid-Open No. 61-76440, and WO2002 / 018322.
  • the filling liquid preferably contains tamibarotene in a content (mass ratio) of 0.1% by mass to 10.0% by mass. If it is 0.1% by mass or more, the number of capsule preparations for taking a desired amount of tamibarotene is not excessively increased, and if it is 10.0% by mass or less, the solubility of tamibarotene is improved. There is a tendency to maintain.
  • the content of tamibarotene in the filling liquid is more preferably 0.1% by mass to 8.0% by mass from the viewpoint of stability over time of the capsule preparation.
  • the content per volume of the tamibarotene filling liquid can be 1 mg / mL to 100 mg / mL, preferably 1 mg / mL to 80 mg / mL. If Tamibarotene is 1 mg / mL or more, the effect of Tamibarotene tends to be sufficiently obtained, and if it is 100 mg / mL or less, good solubility tends to be obtained.
  • the filling liquid contains propylene glycol monocaprylate (propylene glycol monooctanoate) as a base.
  • propylene glycol monocaprylate propylene glycol monooctanoate
  • the propylene glycol monocaprylate used as the base is preferably a grade approved for use as a pharmaceutical additive.
  • the filling liquid may contain an oily base other than propylene glycol monocaprylate from the viewpoint of imparting desired properties to the capsule preparation, such as dissolution of a poorly soluble drug in water.
  • oily bases examples include propylene glycol fatty acid esters other than propylene glycol monocaprylate, sucrose fatty acid esters, sorbitan fatty acid esters, fatty acid triglycerides, polyethylene glycols, animal and vegetable oils, and surfactants. These can be used alone or in combination of two or more.
  • propylene glycol fatty acid ester examples include monooleic acid ester and di (capryl, capric acid) ester.
  • Riquemar PO-100V propylene glycol monooleate, manufactured by Riken Vitamin Co., Ltd.
  • Sunsoft No. 25-ODV manufactured by Taiyo Chemical Co., Ltd.
  • NIKKOL Sefsol-228 Nikko Chemicals Co., Ltd.
  • NIKKOL Sefsol PDD Nikko Chemicals Co., Ltd.
  • fatty acid triglycerides examples include C8-C12 medium chain fatty acid triglycerides.
  • polyethylene glycol examples include polyethylene glycol and methoxy polyethylene glycol.
  • the average molecular weight of the polyethylene glycols is preferably 200 to 1540.
  • Specific examples of polyethylene glycols include polyethylene glycol (macrogol) 200, 300, 400, 600, 1000, 1500, and 1540 described in the Japanese Pharmacopoeia and the Japanese Pharmacopoeia Pharmaceutical Component Standards. .
  • PEG-200 freezing point-50 ° C.
  • PEG-300 freezing point-13 ° C.
  • PEG-400 freezing point 7 ° C.
  • PEG-600 freezing point 20 ° C.
  • Five types of PEG-1000 (freezing point: 37 ° C.) are preferable, and those having a mean molecular weight of 300 PEG-300, 400 PEG-400, and 600 PEG-600 at room temperature are preferable.
  • sucrose fatty acid ester examples include esters of fatty acids having 12 to 20 carbon atoms and sucrose.
  • sorbitan fatty acid ester examples include esters of fatty acids having 12 to 20 carbon atoms and sorbitan.
  • animal and vegetable oils include olive oil, sunflower seed oil, soybean oil, corn oil, fennel oil, sesame oil, safflower oil, wheat germ oil, perilla oil, camellia oil, and whale oil.
  • surfactant include polyoxyethylene hydrogenated castor oil and polysorbate.
  • a base having a low molecular weight may be used.
  • the filling liquid may contain a base having a high melting point from the viewpoint of adjusting the viscosity of the oily base and the dispersibility of the drug.
  • a base having a high melting point from the viewpoint of adjusting the viscosity of the oily base and the dispersibility of the drug.
  • the high melting point base include wax, for example, beeswax, tree wax, whale wax, hydrogenated plant wax, and the like.
  • the film component of the capsule preparation is not particularly limited as long as it is a component usually used in capsule preparations.
  • As the base of the coating component gelatin, agar, pullulan, cellulose, carrageenan and the like can be used alone or in combination.
  • the film component includes additives such as glycerin, sorbitol, mannitol, polyethylene glycol, maltitol, erythritol, xylitol, alginic acid, sodium alginate, and dextrin from the viewpoint of adjusting the strength, disintegration or release characteristics of the film. It may be included.
  • colorants such as caramel, ⁇ -carotene, tar dyes; preservatives such as methylparaben, ethylparaben, propylparaben; BHT, BHA, tocopherol, gallic acid, propyl gallate, ascorbic acid, ascorbic acid Antioxidants or stabilizers such as sodium and stearic esters of ascorbic acid; thickeners or dispersants such as fatty acid monoglycerides and beeswax; solubilizers and solubilizers such as ethanol, ethyl acetate and surfactants; One or more kinds can be added.
  • preservatives such as methylparaben, ethylparaben, propylparaben
  • BHT BHA, tocopherol, gallic acid, propyl gallate, ascorbic acid, ascorbic acid
  • Antioxidants or stabilizers such as sodium and stearic esters of ascorbic acid
  • the coating component is preferably gelatin from the viewpoint of stability over time.
  • the gelatin content can generally be 30% to 90% by mass, preferably 55% to 85% by mass, based on the total mass of the coating component.
  • the coating component may contain glycerin, sorbitol, etc. in order to give elasticity to gelatin.
  • Gelatin may be acid-treated gelatin, alkali-treated gelatin, or chemically modified gelatin.
  • Examples of the chemically modified gelatin include succinylated gelatin.
  • succinylated gelatin is preferable because it is easily soluble and hardly causes a delay in disintegration.
  • the moisture content of the coating component is preferably 1% by mass to 20% by mass, more preferably 5% by mass to 15% by mass, and further preferably 7% by mass to 13% by mass.
  • the shape of the capsule preparation of the present invention is not particularly limited, and is oval type (football type), oblong type (long oval type), round type (spherical type), acorn type, long eggplant type, triangular type. , Diamond type, tube type and the like. From the viewpoint of easy pinching and ease of swallowing, an oval type, an oblong type, or a round type is preferable.
  • the capsule preparation may be a soft capsule or a hard capsule, but is preferably a soft capsule in order to encapsulate a poorly soluble drug in water dissolved in an oil base.
  • a capsule size having a major axis of about 5 mm to about 12 mm is preferable as a soft capsule, and a Japanese standard No. 1 to No. 4 capsule is preferable as a hard capsule.
  • the capsule preparation can be produced by blending each of the above components by a usual method. For example, it can be obtained as follows. At room temperature, the tamibarotene drug substance is added to a propylene glycol monocaprylate ester or a mixed solution with other components as necessary, and the mixture is stirred and dissolved to prepare a filling solution. On the other hand, the coating is formed into a desired shape by heating / dissolving a base such as gelatin and an additional component as necessary, if necessary. Moreover, after shaping
  • the capsule preparation is a soft capsule
  • a filling machine is used to fill a certain amount of the above filling liquid into the capsule and dry it. Get the desired soft capsule.
  • the capsule preparation is a hard capsule
  • a gelatin-based solution is used to seal the joint between the capsule head and the body in a band shape. Get a hard capsule.
  • covered the filling liquid containing a tamibarotene with the film component is obtained.
  • the capsule preparation of the present invention is preferably used for an application according to the application application of tamibarotene, for example, for the treatment of blood cancer or solid cancer.
  • hematological cancer such as acute promyelocytic leukemia (APL), adult T cell leukemia (ATL), multiple myeloma (MM); liver cancer
  • solid cancers such as gastric cancer, breast cancer, esophageal cancer, prostate cancer, gynecological cancer, pancreatic cancer, lung cancer and colon cancer.
  • the present invention also includes a method for treating blood cancer or solid cancer.
  • the treatment method includes administering (specifically, orally administering) the capsule preparation containing tamibarotene to a subject in need of treatment for blood cancer or solid cancer.
  • the capsule preparation may be administered once or multiple times.
  • One or more capsule preparations may be administered at one time.
  • the daily dose of tamibarotene is preferably 1 mg to 16 mg.
  • an amount of tamibarotene necessary for treatment per day may be included in one capsule preparation, and multiple administrations or multiple administrations may be performed at one time. As possible, a reduced amount of tamibarotene may be included in one capsule formulation.
  • Example 1 Insolubilization evaluation The insolubilization of capsule preparations by a combination of a base material for a filling liquid of capsule preparations and a film was examined.
  • Propylene glycol monocaprylate NIKKOL Sefsol-218, Nikko Chemicals
  • propylene glycol monooleate Rosmar PO-100V, Riken Vitamin
  • propylene glycol dicaprate NIKKOL Sefsol PDD
  • NIKKOL Sefsol PDD propylene glycol dicaprylate
  • a liquid and a filling liquid composed only of a polypropylene glycol fatty acid ester not containing tamibarotene were prepared as filling liquid samples.
  • the capsule coating solution 25 g was spread evenly on a stainless steel vat (about 15 cm ⁇ about 11 cm) and allowed to stand at room temperature to obtain a capsule skin sheet. From the obtained sheet, a circular sample having a diameter of 1 cm was punched out and dried in the drying chamber until the moisture content of the soft capsule (9% by mass or less) was obtained, thereby obtaining a test coating sample.
  • a capsule film sample taken out from each filling liquid sample is subjected to a disintegration test at 37 ⁇ 2 ° C. using a disintegration tester (NT-4H, Toyama Sangyo Co., Ltd.), and the film is completely dissolved. As the time of disintegration, the time from the start of the test to the disintegration was measured. The results are shown in Table 1.
  • propylene glycol monooleate which is widely used in pharmaceuticals as a base for filling liquid, causes insolubilization of a coating based on gelatin when combined with tamibarotene.
  • propylene glycol monocaprylate ester did not specifically cause insolubilization of the gelatin-based film, and showed good disintegration of the capsule preparation.
  • the dissolution concentration of tamibarotene at 20 ° C. ⁇ 5 ° C. was 6.3% by mass for propylene glycol monocaprylate, 0.8% by mass for propylene glycol dicaprylate, and propylene glycol dicaprate. It was 0.5 mass% with respect to the phosphonate ester. Therefore, it was found that the solubility of tamibarotene at the specific temperature in propylene glycol monocaprylate was significantly higher than the solubility in propylene glycol dicaprylate and propylene glycol dicaprate.
  • propylene glycol monocaprylate is used in terms of stability over time and the ability to formulate tamibarotene at a high concentration. It has been found that it is best to use the base of the filling liquid.
  • the coating was loaded into a rotary capsule automatic filling machine (manufactured by Toyo Capsule Co., Ltd.), and the filling solution was filled so as to be equivalent to 100 mg per soft capsule to obtain a Tamibarotene capsule containing 2 mg Tamibarotene. Thereafter, PTP packaging was performed to obtain a product.
  • tamibarotene-containing capsule preparation having excellent stability over time.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne une préparation en capsule telle qu'un liquide de remplissage comprenant un tamibarotène et un ester d'acide monocaprylique de propylène glycol, est enrobé d'un composant film.
PCT/JP2013/075926 2013-09-25 2013-09-25 Préparation en capsule Ceased WO2015045037A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/JP2013/075926 WO2015045037A1 (fr) 2013-09-25 2013-09-25 Préparation en capsule

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/JP2013/075926 WO2015045037A1 (fr) 2013-09-25 2013-09-25 Préparation en capsule

Publications (1)

Publication Number Publication Date
WO2015045037A1 true WO2015045037A1 (fr) 2015-04-02

Family

ID=52742244

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2013/075926 Ceased WO2015045037A1 (fr) 2013-09-25 2013-09-25 Préparation en capsule

Country Status (1)

Country Link
WO (1) WO2015045037A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013199458A (ja) * 2012-03-26 2013-10-03 Tmrc Co Ltd カプセル製剤

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU609428B2 (en) * 1986-11-07 1991-05-02 F. Hoffmann-La Roche Ag Use of carboxylic acid amides
WO1993000891A1 (fr) * 1991-07-01 1993-01-21 The Upjohn Company Preparation enterique sensible aux enzymes destinee a une administration orale
EP0619116A2 (fr) * 1993-04-05 1994-10-12 Hoechst Japan Limited Utilisation des rétinoides synthétiques dans l'osteopathie
EP2143428A1 (fr) * 2007-03-30 2010-01-13 TMRC Co., Ltd. Préparation de capsules de tamibarotène
JP2013199458A (ja) * 2012-03-26 2013-10-03 Tmrc Co Ltd カプセル製剤

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU609428B2 (en) * 1986-11-07 1991-05-02 F. Hoffmann-La Roche Ag Use of carboxylic acid amides
WO1993000891A1 (fr) * 1991-07-01 1993-01-21 The Upjohn Company Preparation enterique sensible aux enzymes destinee a une administration orale
EP0619116A2 (fr) * 1993-04-05 1994-10-12 Hoechst Japan Limited Utilisation des rétinoides synthétiques dans l'osteopathie
EP2143428A1 (fr) * 2007-03-30 2010-01-13 TMRC Co., Ltd. Préparation de capsules de tamibarotène
JP2013199458A (ja) * 2012-03-26 2013-10-03 Tmrc Co Ltd カプセル製剤

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013199458A (ja) * 2012-03-26 2013-10-03 Tmrc Co Ltd カプセル製剤

Similar Documents

Publication Publication Date Title
EP2143428B1 (fr) Préparation de capsules de tamibarotène
CA2231342C (fr) Composition pharmaceutique pour administration par voie orale
AU2018100110A4 (en) Ubiquinone And Ubiquinol Compositions, And Methods Relating Thereto
JP2021518429A (ja) 腸溶性ソフトゲルカプセル剤
RU2344810C2 (ru) Новый состав для мягких желатиновых капсул, содержащих ретиноид
KR100679582B1 (ko) 경질 쉘 캡슐용 이부프로펜 용액
CN108295043B (zh) 一种治疗胃溃疡的液晶凝胶纳米粒冻干粉胶囊剂及其制备方法
JP2007529543A (ja) 組織解毒及び健康補助食品並びにそれらを製造及び使用する方法
CN109394724B (zh) 一种丁基苯酞液体硬胶囊制剂及其制备方法
CZ2002694A3 (cs) Biodostupná dávková forma isotretinoinu
WO2015045037A1 (fr) Préparation en capsule
JP2013199458A (ja) カプセル製剤
RU2630606C2 (ru) Устойчивые составы антитромбоцитарных средств, омега-3 жирных кислот и амилозы в мягких желатиновых капсулах
JPH03128322A (ja) ポリプレニル系化合物を含有する医薬組成物およびその製造方法
WO2004073692A1 (fr) Capsule dure de medicament peu hydrosoluble
WO2005046651A1 (fr) Capsules remplies de liquide et renfermant de la doxycycline
KR101096429B1 (ko) 안정성이 향상된 아세클로페낙의 경구용 연질캅셀제
US20230270678A1 (en) Pharmaceutical compositions for improved delivery of therapeutic lipophilic actives
US20080226705A1 (en) Gel delivery system for oral administration of medicaments
JP3131917U (ja) ソフトカプセル
WO2024080884A1 (fr) Compositions pharmaceutiques de trétinoïne et procédés de production de telles compositions
EP2699267A1 (fr) Véhicule liquide pour administration orale d'un agent pharmacologiquement actif
JP6971060B2 (ja) 医薬品組成物
JP2024512659A (ja) 医薬製剤におけるアニオン性キレート剤としてのリン脂質
CN101966168A (zh) 一种速崩型软胶囊的制备方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 13894135

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 13894135

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: JP