WO2010110428A1 - Agent pour prévenir et/ou traiter le prurit - Google Patents

Agent pour prévenir et/ou traiter le prurit Download PDF

Info

Publication number
WO2010110428A1
WO2010110428A1 PCT/JP2010/055384 JP2010055384W WO2010110428A1 WO 2010110428 A1 WO2010110428 A1 WO 2010110428A1 JP 2010055384 W JP2010055384 W JP 2010055384W WO 2010110428 A1 WO2010110428 A1 WO 2010110428A1
Authority
WO
WIPO (PCT)
Prior art keywords
pruritus
pharmaceutically acceptable
acceptable salt
agent
compound
Prior art date
Application number
PCT/JP2010/055384
Other languages
English (en)
Japanese (ja)
Inventor
俊二 九里
史郎 白倉
Original Assignee
協和発酵キリン株式会社
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 協和発酵キリン株式会社 filed Critical 協和発酵キリン株式会社
Publication of WO2010110428A1 publication Critical patent/WO2010110428A1/fr

Links

Classifications

    • 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
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/665—Phosphorus compounds having oxygen as a ring hetero atom, e.g. fosfomycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics

Definitions

  • the present invention relates to a prophylactic and / or therapeutic agent for pruritus containing a compound having a T-type calcium channel antagonistic action or a pharmaceutically acceptable salt thereof as an active ingredient.
  • Pruritus is an itchy sensation that occurs in the surface layer of the skin and the mucous membrane adjacent to the skin, and is often seen in skin diseases accompanied by inflammation, but visceral diseases (endocrine / metabolic diseases, liver / biliary diseases, kidney diseases, etc.), malignant tumors , Blood diseases, neurological diseases, AIDS (acquired immune deficiency syndrome), iron deficiency and pregnancy, parasitic infections, drug side effects, psychogenic. Pruritus is a sensation that can be easily understood as a sensation of urge to scratch, but the mechanism of its expression has not yet been fully elucidated.
  • Atopic dermatitis As specific diseases (including morbidity caused by diseases etc.) for which pruritus is treated, for example, Atopic dermatitis, neurodermatitis, senile dermatitis, seborrheic dermatitis, mesothelitis, eczema / dermatitis, hives, photosensitivity, self-sensitizing dermatitis, urticaria, insect bite
  • skin diseases such as scabies, mycosis, pruritus, hypertrophic scars, psoriasis such as psoriasis vulgaris, blistering, psoriasis, lichen, ringworm, burns, Endocrine / metabolic diseases (thyroid diseases such as thyroid abnormalities, diabetes, etc.), liver / biliary diseases (cirrhosis such as primary biliary cirrhosis, cholestasis, hepatitis, etc.), renal diseases (renal failure such as chronic renal failure) Visceral
  • Pruritus due to pregnancy or side effects of drugs may be treated. Pruritus is a very unpleasant symptom and is often observed to cause sleep disorders. In severe cases, it becomes a serious obstacle to daily life.
  • antihistamines, antiallergic agents, antiserotonin agents, etc. are used as internal preparations, and steroid external preparations, immunosuppressants (Protopic ointment, etc.), menthol, moisturizers, etc. are used as external preparations. Except for some pruritus such as urticaria, the effect on itching is not sufficient.
  • side effects such as central nervous system inhibitory action (drowsiness, malaise, etc.) and disorders to the digestive system are problems in internal medicine.
  • the voltage-gated calcium channel is a protein that penetrates the cell membrane, and is an ion channel that forms a pathway for allowing calcium ions to flow into cells due to a potential difference inside and outside the cells. Due to the difference in electrophysiological properties, five types of voltage-dependent calcium channels of high threshold activation type L, T, N, P / Q and R are known. L-type, N-type, P / Q-type, and R-type are activated by moderate to large depolarization, whereas T-type is activated by small depolarization. T-type calcium channels have been confirmed to be expressed in the brain, heart, kidney, liver and sensory nerves.
  • T-type calcium channel antagonists are targeted for indications such as sleep disorder, epilepsy, hypertension, arrhythmia, renal disorder, diabetes, pain, cancer, etc., and actually have T-type calcium channel antagonism in clinical practice
  • efonidipine lower
  • protective effects on the heart and kidney have been reported (Non-patent Documents 1 and 2).
  • efonidipine as compounds having T-type calcium antagonistic activity, for example, mibefradil (Non-patent document 3), (R) -efonidipine (Non-patent document 4), KYS05049 (Non-patent document 5), nickel chloride (non-patent document 3) Patent Document 6) and the like are known.
  • An object of the present invention is to provide a prophylactic and / or therapeutic agent for pruritus comprising a compound having a T-type calcium channel antagonistic action or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention relates to the following (1) to (12).
  • a prophylactic and / or therapeutic agent for pruritus comprising a compound having a T-type calcium channel antagonistic action or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the agent for preventing and / or treating pruritus according to (2), wherein the low-molecular organic compound or inorganic compound or a pharmaceutically acceptable salt thereof is (R) -ephonidipine.
  • the agent for preventing and / or treating pruritus according to (2), wherein the low molecular organic compound or inorganic compound or a pharmaceutically acceptable salt thereof is nickel chloride hexahydrate.
  • the agent for preventing and / or treating pruritus according to (2), wherein the low-molecular organic compound or inorganic compound or a pharmaceutically acceptable salt thereof is efonidipine monohydrochloride / 1 ethanol solvate.
  • a compound having a T-type calcium channel antagonistic action or a pharmaceutically acceptable salt thereof as an active ingredient for example, atopic Dermatitis, neurodermatitis, senile dermatitis, seborrheic dermatitis, hair dermatitis, eczema / dermatitis, hives, photosensitivity, self-sensitizing dermatitis, rash, insect bite, scabies
  • skin diseases such as mycosis, pruritus, hypertrophic scar, psoriasis such as psoriasis vulgaris, blistering, psoriasis, lichen, ringworm, burns, Liver and biliary tract diseases (cirrhosis such as primary biliary cirrhosis, cholestasis, hepatitis, etc.), renal diseases (renal failure such as chronic renal failure, renal dialysis, etc.
  • the compound having T-type calcium antagonistic activity which is an active ingredient of the agent for preventing and / or treating pruritus according to the present invention, may be any compound as long as it has T-type calcium channel antagonistic activity.
  • it may be a non-peptide compound, may be a low molecular compound or a high molecular compound, and may be an organic compound or an inorganic compound.
  • the low molecular weight organic compound means an organic compound having a small molecular weight, and examples thereof include an organic compound having a molecular weight of 1000 or less.
  • Atopic dermatitis As a disease (including a morbid state resulting from a disease etc.) with a specific pruritus that is a target of the agent for preventing and / or treating pruritus of the present invention, Atopic dermatitis, neurodermatitis, senile dermatitis, seborrheic dermatitis, mesothelitis, eczema / dermatitis, hives, photosensitivity, self-sensitizing dermatitis, urticaria, insect bite
  • diseases involving skin lesions such as scabies, mycosis, pruritus, hypertrophic scars, psoriasis vulgaris, blistering, psoriasis, lichen, ringworm, burns, Liver and biliary tract diseases (cirrhosis such as primary biliary cirrhosis, cholestasis, hepatitis, etc.), renal diseases (renal failure such as chronic renal failure, renal di
  • the prevention and / or treatment agent for pruritus of the present invention can be applied to the prevention and / or treatment of itching due to pregnancy and side effects of drugs.
  • the disease with pruritus that is prevented and / or treated with the preventive and / or therapeutic agent according to the present invention is preferably a disease with intractable pruritus that exhibits resistance to an antihistamine, specifically, for example, Examples include atopic dermatitis or renal failure with pruritus, renal dialysis, or cholestasis.
  • Examples of compounds that antagonize the T-type calcium channel used in the present invention include mibefradil, efonidipine, (R) -efonidipine, (R) -Efonidipine, ethosuximide, zonisamide, flunarizine (Flunarizine), KYS05049, KYS05090, TTL-1177, NNC55-0396, and other organic compounds, or NiCl 2 (nickel chloride) and other inorganic compounds.
  • the compounds described in the following documents or patents can also be cited as examples of compounds that antagonize the T-type calcium channel used in the present invention, and these compounds are synthesized by the methods described in the respective documents or patents.
  • pharmaceutically acceptable salts of these compounds can also be used.
  • Pharmaceutically acceptable salts of these compounds include, for example, pharmaceutically acceptable acid addition salts, metal salts, ammonium salts, organic amine addition salts, amino acid addition salts and the like.
  • examples of pharmaceutically acceptable acid addition salts of these compounds include inorganic acid salts such as hydrochloride, hydrobromide, nitrate, sulfate, phosphate, acetate, oxalate, and maleate.
  • Organic acid salts such as fumarate, citrate, benzoate, methanesulfonate, and the like.
  • Examples of pharmaceutically acceptable metal salts include alkali metal salts such as sodium salt and potassium salt, Examples thereof include alkaline earth metal salts such as magnesium salt and calcium salt, aluminum salt and zinc salt.
  • Examples of pharmaceutically acceptable ammonium salts include salts such as ammonium and tetramethylammonium.
  • Examples of acceptable organic amine addition salts include addition salts such as morpholine and piperidine.
  • Examples of pharmaceutically acceptable amino acid addition salts include lysine and glycine. Phenylalanine, aspartic acid, addition salts of the glutamic acid and the like.
  • These compounds and pharmaceutically acceptable salts thereof may exist in the form of adducts with water or various solvents (ethanol, propyl alcohol, acetone, etc.), and these adducts are also used in the present invention. be able to.
  • refractory pruritus that is resistant to antihistamines, such as pruritus associated with atopic dermatitis, pruritus associated with renal failure or renal dialysis, or cholestatic pruritus
  • endogenous opioids in the blood Known to increase [Acta Dermato Venereologica, 1995, 75, 9-11; Nephrology Dialysis Transplantation, 2001, 16, 1953-1954; British Medical Journal, 1988, 297, 1501-1504].
  • opioid antagonists are effective against these intractable pruritus, suggesting that endogenous opioids are associated with the pathology of these intractable pruritus [Journal of American Academy of Dermatology, 1999, 41, 533-539; Lancet, 1996, 348, 1552-1554; Journal of Hepatology ( Journal of Hepatology), 2002, 37, 717-722].
  • Opioid antagonists also suppress pruritus caused by endogenous pruritus-inducing substances such as histamine, substance P, and serotonin [Journal of Investigative Dermatology, 1982, 78, 82-83; European Journal of Pharmacology, 2003, 477, 29-35; Neuroscience Research, 1999, 35 77-83], endogenous opioids are considered to be mediators that are not limited to refractory pruritus but are common to the transmission of various pruritus. Therefore, the morphine-induced pruritus model [Journal of Biomedical Science, 2000, Vol. 7, pp. 248-252] was used for the evaluation of itching. Hereinafter, the present invention will be described more specifically based on examples.
  • Test compounds in the evaluation of pruritus-suppressing effects of T-type calcium channel antagonists include mibefradil dihydrochloride (EP0268148, US4808605), efonidipine monohydrochloride, 1 ethanol hydrate [Chemical Pharmaceutical Bretan (Chem. Pharm. Bull), 1992, 40, NZ-105 in pages 2362-2369], (R) -Ehonidipine [Chem. Pharm. Bull, 1992, 40, 2377 -2381 (R) -6], KYS05049 (compound 9a in Non-Patent Document 5), NiCl 2 ⁇ 6H 2 0 (nickel chloride hexahydrate, Cat. No. 242-23, Lot. No.
  • Test Example 1 Drug Itching Inhibition Action in Morphine-Induced Pruritic Mice Using a microsyringe with a 30-gauge injection needle between the 5th and 6th lumbar vertebrae of male ddY mice, morphine (1 nmol / 5 ⁇ L in physiological saline) Dissolution) or saline was administered intrathecally. A group to which only morphine was administered was defined as a control group (“control group” in the table), and a group to which only physiological saline was administered was defined as a physiological saline administration group (“physiological saline group” in the table).
  • the number of scratching behaviors in the hind limbs observed immediately after morphine administration was measured for 30 minutes.
  • movement the series of operation
  • the test compounds mibefradil dihydrochloride, efonidipine monohydrochloride / 1 ethanol solvate, (R) -efonidipine and KYS05049 were administered 30 minutes prior to morphine administration.
  • Mibefradil dihydrochloride is dissolved in physiological saline, and efonidipine monohydrochloride / ethanol monohydrate, (R) -efonidipine and KYS05049 are suspended in 0.5% methylcellulose solution, and each is intraperitoneally (i) in a volume of 10 mL / kg. P.).
  • NiCl 2 ⁇ 6H 20 was dissolved in physiological saline, and 5 ⁇ L / mouse was administered intrathecally (it) simultaneously with morphine.
  • Tables 1, 2, 3 and 4 show the effects of mibefradil, efonidipine, (R) -ephonidipine, KYS05049 and nickel chloride on the scratching behavior of morphine-induced pruritic mice.
  • Mibefradil (10 mg / kg, ip), efonidipine (100 mg / kg, ip), (R) -efonidipine (100 mg / kg, ip), KYS05049 (3, 10 mg / kg) kg, ip) and nickel chloride (1, 10 nmol, it) suppressed the increased scratching behavior observed in morphine-induced pruritic mice.
  • the administration route of the medicament of the present invention is not particularly limited, and the most effective administration route for prevention and / or treatment can be appropriately selected from either oral administration or parenteral administration such as intravenous administration.
  • preparations suitable for oral administration include tablets and the like, and examples of preparations suitable for parenteral administration include injections and the like.
  • Formulations suitable for parenteral administration preferably comprise a sterile aqueous solution containing the active compound that is isotonic with the blood of the recipient.
  • a solution for injection is prepared using a carrier comprising a salt solution, a glucose solution, or a mixture of salt water and a glucose solution.
  • auxiliary agents selected from diluents, preservatives, flavors, excipients, disintegrants, lubricants, binders, surfactants, plasticizers and the like. Ingredients can also be added.
  • the dose and frequency of administration of the medicament of the present invention vary depending on the dosage form, patient age, body weight, nature or severity of symptoms to be treated, but usually 0.01 mg to 1 g / kg per adult for oral administration. Preferably, 0.05 to 50 mg / kg, more preferably 3 to 30 mg / kg is administered once to several times a day.
  • parenteral administration such as intravenous administration
  • usually 0.001-1 to 1 g / kg, preferably 0.01 to 10 mg / kg, more preferably 1 to 10 mg / kg is administered once a day to several times per adult.
  • these doses and number of doses vary depending on the various conditions described above. In the following, embodiments of the present invention will be described with reference to examples, but the present invention is not limited to these examples.
  • a tablet having the following composition is prepared by a conventional method. 40 g of mibefradil, 286.8 g of lactose and 60 g of potato starch are mixed, and 120 g of a 10% aqueous solution of hydroxypropylcellulose is added thereto. The obtained mixture is kneaded by a conventional method, granulated and dried, and then sized to obtain granules for tableting.
  • Injection (mibefradil) An injection having the following composition is prepared by a conventional method. Add 1 g of mibefradil to distilled water for injection, mix, add hydrochloric acid and aqueous sodium hydroxide to adjust the pH to 7, and make the total volume 1000 mL with distilled water for injection. The obtained mixed solution is aseptically filled into glass vials by 2 mL to obtain an injection (containing 2 mg of active ingredient per vial).
  • Formulation Mibefradil 2 mg Hydrochloric acid appropriate amount Sodium hydroxide aqueous solution appropriate amount distilled water for injection appropriate amount 2.00 mL
  • a prophylactic and / or therapeutic agent for pruritus containing a compound having a T-type calcium channel antagonistic action or a pharmaceutically acceptable salt thereof as an active ingredient can be provided.

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (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)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne, entre autres, un agent destiné à prévenir et/ou à traiter le prurit et qui comprend comme principe actif un composé possédant une activité antagoniste sur un canal calcique de type T, ou un sel pharmaceutiquement acceptable de ce composé.
PCT/JP2010/055384 2009-03-27 2010-03-26 Agent pour prévenir et/ou traiter le prurit WO2010110428A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2009-078349 2009-03-27
JP2009078349 2009-03-27

Publications (1)

Publication Number Publication Date
WO2010110428A1 true WO2010110428A1 (fr) 2010-09-30

Family

ID=42781118

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2010/055384 WO2010110428A1 (fr) 2009-03-27 2010-03-26 Agent pour prévenir et/ou traiter le prurit

Country Status (1)

Country Link
WO (1) WO2010110428A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014021383A1 (fr) 2012-07-31 2014-02-06 協和発酵キリン株式会社 Composé hétérocyclique à cycles condensés
US9000186B2 (en) 2011-02-01 2015-04-07 Kyowa Hakko Kirin Co., Ltd. Ring-fused heterocyclic derivative
JP7478894B1 (ja) 2022-11-30 2024-05-07 花王株式会社 痒みの予防又は改善剤
JP7478895B1 (ja) 2022-11-30 2024-05-07 花王株式会社 痒みの予防又は改善剤

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002505268A (ja) * 1998-03-06 2002-02-19 ロレアル 局所使用組成物におけるナトリウムチャンネル活性阻害化合物の使用
WO2008133867A1 (fr) * 2007-04-26 2008-11-06 Merck & Co., Inc. Dérivés d'indole 2-substitués comme bloqueurs de canaux calciques

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002505268A (ja) * 1998-03-06 2002-02-19 ロレアル 局所使用組成物におけるナトリウムチャンネル活性阻害化合物の使用
WO2008133867A1 (fr) * 2007-04-26 2008-11-06 Merck & Co., Inc. Dérivés d'indole 2-substitués comme bloqueurs de canaux calciques

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
HATTORI, T. ET AL.: "Interaction between stannous chloride and calcium channel blockers in frog neuromuscular transmission", RESEARCH COMMUNICATIONS IN CHEMICAL PATHOLOGY AND PHARMACOLOGY, vol. 75, no. 2, 1992, pages 243 - 6 *
RHIM, H. ET AL.: "Synthesis and biological activity of 3, 4-dihydroquinazolines for selective T-type Ca2+ channel blockers", BIOORG. MED. CHEM. LETT, vol. 15, no. 2, 2005, pages 283 - 6 *
TANAKA, H. ET AL.: "Pathophysiological significance of T-type Ca2+ channels: T-type Ca2+ channels and drug development", J PHARMACOL SCI, vol. 99, no. 3, 2005, pages 214 - 20 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9000186B2 (en) 2011-02-01 2015-04-07 Kyowa Hakko Kirin Co., Ltd. Ring-fused heterocyclic derivative
WO2014021383A1 (fr) 2012-07-31 2014-02-06 協和発酵キリン株式会社 Composé hétérocyclique à cycles condensés
JP7478894B1 (ja) 2022-11-30 2024-05-07 花王株式会社 痒みの予防又は改善剤
JP7478895B1 (ja) 2022-11-30 2024-05-07 花王株式会社 痒みの予防又は改善剤

Similar Documents

Publication Publication Date Title
AU2021202956B2 (en) Method of treatment with tradipitant
KR101673731B1 (ko) 벰루페닙 및 mdm2 억제제의, 증식성 질환 치료용 복합 요법
WO2004043389B1 (fr) Procedes de traitement du cancer et procedes connexes
KR20180113976A (ko) 암을 치료하기 위한 테트라사이클릭 퀴놀론 유사체의 병행 요법
JP6837486B2 (ja) 加齢に関連する認知障害及び神経炎症を予防及び／又は治療する方法
TW200829244A (en) Therapeutic combinations 482
US20220184075A1 (en) Pharmaceutical composition containing hdac6 inhibitor as active ingredient for prevention or treatment of itching
AU2002315814B2 (en) Medicinal composition for treatment of interstitial cystitis
WO2013002365A1 (fr) Agent antiprurigineux
CN109316480A (zh) 组合als疗法
JP2022507533A (ja) 肺動脈性高血圧症および他疾患に関連する肺動脈性肺高血圧症の治療法
TW202114694A (zh) 四環化合物及其鹽類、組合物、及彼等之使用方法
JP2011512399A (ja) 卵巣癌を治療するための、パクリタキセルを含む配合剤
WO2010110428A1 (fr) Agent pour prévenir et/ou traiter le prurit
TW201817425A (zh) 用於治療非酒精性脂肪肝疾病之醫藥組成物及方法
RU2611341C2 (ru) Способ увеличения эффективности терапии аутоиммунных заболеваний, таких как ревматоидный артрит
JP2010106019A (ja) リマプロストを含有してなる癌化学療法に起因する末梢神経障害予防、治療および／または症状軽減剤
WO2019242688A1 (fr) Combinaison d'acide 3-hydroxyaminobenzoïque et de sorafénib pour le traitement de cancers
CN113329749A (zh) 用于治疗葡萄膜黑色素瘤的联合疗法
US20230038138A1 (en) Combination therapy for treating cancer
WO2006041120A1 (fr) Préparation pharmaceutique
TWI356699B (en) Agent for treating interstitial cystitis and agent
JP2010526073A (ja) 癌または前癌性症状およびその他の症状の治療のためのジヒドロピリジン誘導体
JP5830983B2 (ja) 抗癌剤の副作用軽減剤
CN107613966A (zh) 阿片类物质和n‑酰基乙醇胺的组合

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: 10756224

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: 10756224

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: JP