WO2022255790A1 - 폐섬유화증의 예방 또는 치료용 약학 제제 - Google Patents
폐섬유화증의 예방 또는 치료용 약학 제제 Download PDFInfo
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- WO2022255790A1 WO2022255790A1 PCT/KR2022/007778 KR2022007778W WO2022255790A1 WO 2022255790 A1 WO2022255790 A1 WO 2022255790A1 KR 2022007778 W KR2022007778 W KR 2022007778W WO 2022255790 A1 WO2022255790 A1 WO 2022255790A1
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- Prior art keywords
- pulmonary fibrosis
- compound
- formula
- administration
- nintedanib
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Images
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
- A61K31/33—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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present disclosure relates to pharmaceutical formulations for treating or preventing pulmonary fibrosis. That is, the present disclosure relates to the pharmaceutical use of a specific compound for the treatment or prevention of pulmonary fibrosis.
- the present disclosure also relates to combination formulations, ie, combination therapy, for the treatment or prevention of pulmonary fibrosis.
- Pulmonary fibrosis is a disease in which the lungs gradually become stiff and their function deteriorates, leading to death due to respiratory failure.
- Causes include rheumatoid disease, radiation, mold exposure, etc., and there is also idiopathic pulmonary fibrosis for which no specific cause can be found.
- pulmonary fibrosis The treatment of pulmonary fibrosis is based on taking drugs that slow down the progress of fibrosis as much as possible, and lung transplantation should be considered in severe cases.
- pirfenidone the prescription drug for pulmonary fibrosis in clinical use: pirfenidone and nintedanib.
- the present disclosure is to provide a pharmaceutical agent useful for preventing or treating pulmonary fibrosis.
- Another aspect of the present disclosure is to provide a method for preventing or treating pulmonary fibrosis.
- one aspect of the present disclosure is to prevent or treat pulmonary fibrosis (pulmonary fibrosis) comprising a pyrimidine-4-carboxamide compound of Formula 1 as an active ingredient Provides a pharmaceutical preparation for use.
- the compound is a compound included in the formula disclosed in International Patent Application Publication No. WO2011-139107.
- the compound is an 11 ⁇ -HSD1 (11 ⁇ -hydroxysteroid dehydrogenase type 1) enzyme inhibitor and is mainly studied for use in the treatment of metabolic diseases such as diabetes and non-alcoholic steatohepatitis. (International Patent Application Publication WO2020-022708)
- the compound of Formula 1 may be prepared by the method disclosed in International Patent Application Publication No. WO2011-139107.
- the present disclosure also provides a method for treating, improving or preventing pulmonary fibrosis, comprising administering a therapeutically or prophylactically effective amount of the compound of Formula 1 to a subject in need of treatment or prevention of pulmonary fibrosis. do. That is, the present disclosure provides a pharmaceutical use of the compound of Formula 1 for treating or preventing pulmonary fibrosis.
- prevention includes prevention of recurrence, expansion, or development of pulmonary fibrosis in a patient.
- treatment includes eradication, elimination, or control of pulmonary fibrosis, and minimizing or delaying the spread of pulmonary fibrosis.
- the pulmonary fibrosis is pulmonary fibrosis induced by drug therapy (eg, anti-cancer drug therapy) or radiation exposure. In another aspect of the present disclosure, the pulmonary fibrosis is idiopathic pulmonary fibrosis.
- Another aspect of the present disclosure is a lung, comprising the compound of Formula 1 as an active ingredient, and further comprising Nintedanib (CAS number: 656247-17-5) or a pharmaceutically acceptable salt thereof as a second active ingredient.
- a pharmaceutical preparation for preventing or treating fibrosis is provided. That is, another aspect of the present disclosure provides a complex preparation of the two active ingredients for preventing or treating pulmonary fibrosis, that is, a combination therapy thereof.
- the compound of Formula 1 and the Nintedanib component synergistically increase the therapeutic or preventive effect of pulmonary fibrosis.
- Acid addition salts may be used as pharmaceutically acceptable salts of Nintedanib, and include salts of active compounds prepared with relatively non-toxic acids. Acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either pure or in a suitable inert solvent.
- Examples of pharmaceutically acceptable acid addition salts are acetic acid, propionic acid, isobutyric acid, oxalic acid, maleic acid, malonic acid, benzoic acid, succinic acid, suberic acid, fumaric acid ( fumaric), mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric acid, tartaric acid, methanesulfonic, and their analogues.
- Hydrogen chloride hydrogen bromide, nitric acid, carbonic acid, monohydrogencarbonic, phosphoric, monohydrogenphosphate, dihydrogenphosphate, sulfuric acid, monohydrosulfuric acid, hydrogen iodide or phosphorous acid ( phosphorous acid) and its analogues.
- salts of amino acids such as alginate and analogs thereof and analogs of organic acids such as glucuronic or galactunoric acids and analogs thereof.
- the ethanesulfonic acid of nintedanib can be used.
- compound of Formula 1 or “nintedanib” refers to the compound of Formula 1 and nintedanib, as well as clathrates, hydrates, solvates, or polymorphs (polymorphs) thereof. meaning to include
- polymorph refers to a solid crystal form of a compound of the present invention or a complex thereof. Different polymorphs of the same compound exhibit different physical, chemical and/or spectral properties. Differences in terms of physical properties include, but are not limited to, stability (e.g. heat or light stability), compressibility and density (important for formulation and product manufacturing), and dissolution rate (which may affect bioavailability). It doesn't. Differences in stability may be due to chemical reactivity changes (e.g. differential oxidation such as faster discoloration when composed of one polymorph than when composed of another polymorph) or mechanical properties (e.g.
- kinetically Tablet fragments stored as the preferred polymorph may be thermodynamically converted to a more stable polymorph) or both (tablets of one polymorph are more susceptible to degradation at high humidity).
- Other physical properties of polymorphs can affect their processing. For example, one polymorph may be more likely to form solvates, or may be more difficult to filter or wash, than another polymorph, eg, due to its shape or particle size distribution.
- solvent compound refers to a compound of the present invention comprising a stoichiometric or non-stoichiometric amount of a solvent bound by non-covalent intermolecular forces.
- Preferred solvents are volatile, non-toxic, and can be administered in very small amounts to humans.
- hydrate refers to a compound of the present invention that contains a stoichiometric or non-stoichiometric amount of water bound by non-covalent intermolecular forces.
- clathrate refers to a compound of the present invention in the form of a crystal lattice containing spaces (eg, channels) in which guest molecules (eg, solvent or water) are confined.
- prodrug refers to hydrolysis, oxidation and other reactions under biological conditions (ex vivo or in vivo) to provide an active compound, particularly a compound of the present invention.
- prodrugs means a compound of the present invention capable of Examples of prodrugs include biohydrolyzable amides, biohydrolyzable esters, biohydrolyzable carbamates, biohydrolyzable carbonates, biohydrolyzable ureides ( ureides), and compounds that are biohydrolyzed to yield compounds of the present invention, including biohydrolyzable moieties, such as biohydrolyzable phosphate analogues.
- the prodrug of the compound having a carboxyl functional group is a lower alkyl ester of a carboxylic acid.
- Carboxylic esters are commonly formed by esterifying a portion of a carboxylic acid present in a molecule.
- Prodrugs are described in Burger's Medicinal Chemistry and Drug Discovery 6th ed. (Donald J. Abrahamed., 2001, Wiley) and Design and Application of Prodrugs (H. Bundgaard ed., 1985, Harwood Academic Publishers Gmfh).
- a compound of the present invention is generally administered in a therapeutically effective amount.
- the compound(s) of the present invention can be administered by any suitable route, in the form of a pharmaceutical composition suitable for such route, and in a dosage effective for the intended treatment.
- An effective dosage is generally from about 0.01 to about 50 mg/kg of body weight/day, preferably from about 0.05 to about 20 mg/kg/day, in single or divided administration. Dosage levels below the lower end of this range may be suitable depending on the age, species, and disease or condition being treated. In other cases, still larger doses can be used without detrimental side effects. Larger doses may be divided into several smaller doses for administration throughout the day. Methods for determining the appropriate dosage are well known in the art.
- the dosage of each active ingredient may be the same as the dosage when administered alone or reduced by 10-30% by weight compared to single administration.
- the compound of Formula 1 when used in combination, may be administered in an amount of 0.1 to 1 part by weight relative to the dose of Nintedanib.
- Nintedanib dosages are well known in the art (see Ofev® dosages)
- the present disclosure treats pulmonary fibrosis by administering to a subject a therapeutically effective amount of the compound of Formula 1 and a therapeutically effective amount of the second active ingredient Nintedanib or a pharmaceutically acceptable salt thereof Or provide a way to prevent it.
- one of the plurality of active ingredients can be given in multiple doses, or all in multiple doses. If not simultaneous, the timing between multiple doses may vary arbitrarily from greater than 0 weeks to less than 20 weeks.
- combination methods, compositions and formulations are not limited to the use of only two agents, and multiple therapeutic combinations are also envisioned.
- a dosage regimen for treating, preventing, or ameliorating a condition may be arbitrarily changed depending on various factors. These factors include the individual's age, weight, sex, diet, and medical condition, as well as the disorder the individual suffers from.
- the pharmaceutical agents comprising the combination therapy disclosed herein are optionally combined in a single dosage form or primarily separate dosage forms for co-administration.
- the formulation may be a kit formulation in which two active ingredients are separately included.
- the pharmaceutical agents constituting the combination treatment may also be administered sequentially with either agent being administered by a regimen requiring two-step administration.
- a two-step dosing regimen may require sequential administration of the active agents or spaced-apart administration of separate active agents.
- the time period between multiple administration steps ranges from a few minutes to a few minutes depending on the characteristics of each pharmaceutical agent, such as potency, solubility, bioavailability, plasma half-life and kinetic profile of the pharmaceutical agent. up to several hours Circadian variation in target molecule concentration is used to determine the optimal dosing interval.
- another aspect of the present disclosure provides a pharmaceutical formulation comprising the compound of Formula 1, and a pharmaceutically acceptable carrier or additive;
- a pharmaceutical preparation comprising the compound of Formula 1, Nintedanib or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or additive is provided.
- pharmaceutically acceptable means suitable for use as a pharmaceutical preparation, generally considered safe for such use, and officially approved for such use by a national regulatory agency or approved by the Korean Pharmacopoeia or the United States Means in the pharmacopeia list.
- the active ingredient or active ingredients described herein can be administered as follows.
- a plurality of active ingredients according to the present invention may be included together in one formulation, or a plurality of active ingredients may be included in separate formulations and taken together.
- the active ingredients according to the present invention may be administered intranasally, and nasal administration may be particularly preferred for the pharmaceutical use of the present disclosure.
- nasal administration is a concept including conventional inhalant administration.
- intranasal administration is meant delivery of a composition into the nose and nasal cavities through one or both of the nose or nasal passages, and includes delivery by a spray mechanism or droplet mechanism or delivery by aerosolization of an active ingredient.
- Administration of the composition by inhalation may be through the nose or mouth via delivery by a nebulizer or droplet mechanism.
- compositions of the present invention may be formulated by methods well known to those skilled in the art, for example, with representative solubilizing, diluting, or dispersing substances such as saline, preservatives such as benzyl alcohol. , absorption enhancers and the like, but is not limited thereto.
- a liquid pharmaceutical composition may be prepared by the same method as an oral administration composition described later.
- Such nasal administration may be performed using an intranasal delivery device well known in the art to which the present invention pertains, and propellants such as fluorocarbon and hydrofluoroalkane may be used in such a device.
- propellants such as fluorocarbon and hydrofluoroalkane may be used in such a device.
- the compound of the present invention can be administered orally, and oral is a concept including swallowing.
- Oral administration allows the compounds of the present invention to enter the gastrointestinal tract or be directly absorbed from the mouth into the bloodstream, eg, by buccal or sublingual administration.
- compositions suitable for oral administration may be in solid, liquid, gel, or powder form, and may have formulations such as tablets, lozenges, capsules, granules, powders, and the like. .
- compositions for oral administration may optionally be enteric coated and exhibit delayed or sustained release through the enteric coating. That is, the composition for oral administration according to the present invention may be a formulation having an immediate or modified release pattern.
- Liquid formulations may include solutions, syrups and suspensions, and such liquid compositions may be contained in soft or hard capsules.
- Such formulations may include a pharmaceutically acceptable carrier such as water, ethanol, polyethylene glycol, cellulose, or oil.
- the formulation may also contain one or more emulsifying and/or suspending agents.
- the amount of active ingredient drug may be present from about 0.05% to about 95% by weight, more typically from about 2% to about 50% by weight of the total weight of the tablet.
- Tablets may also contain a disintegrant comprising from about 0.5% to about 35% by weight, more usually from about 2% to about 25% by weight of the dosage form.
- disintegrants include, but are not limited to, lactose, starch, sodium starch glycolate, crospovidone, croscarmellose sodium, maltodextrin, or mixtures thereof.
- Suitable glidants included for making into tablets may be present in amounts from about 0.1% to about 5% by weight, and include talc, silicon dioxide, stearic acid, calcium, zinc or magnesium stearate, sodium stearyl fumarate, and the like. It can be used as a lubricant, but the present invention is not limited to these types of additives.
- Gelatin polyethylene glycol, sugar, gum, starch, polyvinylpyrrolidone, hydroxypropylcellulose, hydroxypropylmethylcellulose, etc. may be used as a binder for preparing tablets.
- Mannitol, xylitol, lactose, dextrose, sucrose, sorbitol, starch, microcrystalline cellulose, etc. may be used as suitable diluents for preparing tablets, but the present invention is not limited to these types of additives. .
- the solubilizing agent that may optionally be included in the tablet may be used in an amount of about 0.1% to about 3% by weight based on the total weight of the tablet, for example, polysorbate, sodium lauryl sulfate, sodium dodecyl sulfate, propylene carbonate, Diethylene glycol monoethyl ether, dimethylisosorbide, polyoxyethylene glycolated natural or hydrogenated castor oil, HCOR TM (Nikkol), oleyl ester, Gelucire TM , caprylic/caprylic mono/ Diglyceride, sorbitan fatty acid ester, Solutol HS TM and the like may be used in the pharmaceutical composition according to the present invention, but the present invention is not limited to specific types of these solubilizers.
- Compounds of the present invention may be administered directly into the bloodstream, muscle, or intestine.
- Suitable methods for parenteral administration include intravenous, intramuscular, subcutaneous intraarterial, intraperitoneal, intrathecal, intracranial injection, and the like.
- Suitable devices for parenteral administration include injectors (including needle and needleless syringes) and infusion methods.
- compositions for parenteral administration may be formulations with an immediate or modified release pattern, and the modified release pattern may be a delayed or sustained release pattern.
- parenteral formulations are liquid compositions, and these liquid compositions are aqueous solutions containing the active ingredient, salt, buffer, tonicity agent and the like according to the present invention.
- Parenteral formulations may also be prepared in dried form (eg lyophilized) or as sterile non-aqueous solutions. These formulations may be used with a suitable vehicle such as sterile water. Solubility-enhancing agents may also be used in the preparation of parenteral solutions.
- the compounds of the present invention may be administered topically to the skin or transdermally.
- Formulations for this topical administration include lotions, solutions, creams, gels, hydrogels, ointments, foams, implants, patches, and the like.
- Pharmaceutically acceptable carriers for topical formulations may include water, alcohol, mineral oil, glycerin, polyethylene glycol, and the like. Topical administration can also be performed by electroporation, iontophoresis, phonophoresis, and the like.
- compositions for topical administration may be formulations with an immediate or modified release pattern, and the modified release pattern may be a delayed or sustained release pattern.
- the present disclosure provides a pharmaceutical formulation useful for the treatment or prevention of pulmonary fibrosis, comprising the compound of Formula 1 as an active ingredient. That is, the present disclosure provides a pharmaceutical use of the compound of Formula 1 useful for the treatment or prevention of pulmonary fibrosis.
- the present disclosure also provides a pharmaceutical formulation useful for the treatment or prevention of pulmonary fibrosis, comprising two active ingredients of a compound of Formula 1 and Nintedanib or a pharmaceutically acceptable salt thereof. That is, the present disclosure provides a combination therapy showing a synergistic synergistic effect useful for the treatment or prevention of pulmonary fibrosis.
- FIG. 2 is a graph showing the quantification of the degree of collagen deposition using an image program after taking a photo of the irradiated lung tissue under a microscope when each test substance was orally administered to a pulmonary fibrosis induced mouse model by irradiation.
- FIG. 3 is a graph showing the quantification of mRNA expression of the col1a1 gene by extracting RNA from lung tissue and using a qPCR method when each test substance was orally administered in a bleomycin-induced pulmonary fibrosis mouse model.
- FIG. 4 is a graph showing the quantification of mRNA expression of the TGFb gene by extracting RNA from lung tissue and using a qPCR method when each test substance was orally administered in a bleomycin-induced pulmonary fibrosis mouse model.
- Figure 5 is a graph quantifying by measuring the amount of hydroxyproline using the ELISA method after obtaining a lysate by dissolving lung tissue when each test substance was orally administered in a pulmonary fibrosis induced mouse model by bleomycin.
- mice C57BL/6 8-week-old male mice were orally administered with the test substance, and 1 hour later, radiation (90Gy, 4 mm collimator) was irradiated to the chest with a size of 3 mm. Afterwards, the test substance was orally administered twice a day for 14 days and then autopsied. After fixing the lung tissue of the mouse with 10% formalin, paraffin sections were made and the degree of collagen deposition in the tissue was confirmed using trichrome staining. The composition of the test group was shown in Table 1 below.
- test group test substance 1 dose route of administration number of administrations G1 Vehicle - oral- 2 times a day, 14 days G2 Nintedanib 30 mg/kg oral- 2 times a day, 14 days G3 Formula 1 compound 10 mg/kg oral- 2 times a day, 14 days G4 Formula 1 compound + nintedanib 10 + 30 mg/kg oral- 2 times a day, 14 days
- mice were respiratory anesthetized using isoflurane. Thereafter, an incision was made in the middle of the neck to expose the airway. 1.25 mg/kg of bleomycin dissolved in saline solution was slowly injected into the exposed upper respiratory tract using an insulin syringe. Then, the insulin syringe was removed and the incision was sutured. Afterwards, the test substance was orally administered twice a day for 14 days and then autopsied. After fixing the left lung tissue of the mouse with 10% formalin, paraffin sections were made and the degree of lung fibrosis was evaluated using the H&E staining method. The right lung had tissue lysed for qPCR and hydroxyproline measurements. Then, it was used in each experiment to evaluate the expression of lung fibrosis-related genes and the degree of collagen deposition in the lungs. The composition of the test group was shown in Table 2 below.
- test group test substance 1 dose route of administration number of administrations G1 Vehicle (normal group) - oral- 2 times a day, 14 days G2 Vehicle (trigger group) - oral- 2 times a day, 14 days G3 Formula 1 compound 30 mg/kg oral- 2 times a day, 14 days G4 Formula 1 compound 100 mg/kg oral- 2 times a day, 14 days G5 Formula 1 compound 200 mg/kg oral- 2 times a day, 14 days G6 Formula 1 compound + nintedanib 60 + 30 mg/kg oral- 2 times a day, 14 days G7 Nintedanib 60 mg/kg oral- 2 times a day, 14 days
- Example 1 Anti-fibrotic efficacy of the compound of Formula 1 in animal models of pulmonary fibrosis
- a test substance was administered to a mouse model of radiation-induced pulmonary fibrosis and autopsied.
- Lung tissues of mice were fixed in 10% neutral formalin for one day, and paraffin sections were made. In order to remove the paraffin around the tissue, it was reacted with xylene, 95, 90, and 70% ethanol solutions for 5 minutes each in order.
- xylene, 95, 90, and 70% ethanol solutions for 5 minutes each in order.
- To activate the tissue antigen the tissue was immersed in a 0.1 M citric acid (pH 6.0) solution and boiled for 20 minutes.
- the anti-fibrotic efficacy of inhibiting collagen deposition was confirmed in all test substance administration groups compared to the vehicle group (G1).
- the test groups showing high significance were the group administered with nintedanib alone (G2) and the group administered with nintedanib and the compound of Formula 1 in combination (G4).
- the group administered with nintedanib and the compound of Formula 1 in combination (G4) showed better efficacy.
- the compound of Formula 1 significantly inhibits collagen deposition, which is a primary evaluation index of pulmonary fibrosis, and in particular, when administered in combination with nintedanib, the effect was confirmed to be superior to that of nintedanib alone.
- Example 2 Anti-fibrotic efficacy of the compound of Formula 1 in animal models of pulmonary fibrosis
- the test substance was administered to the bleomycin-induced pulmonary fibrosis mouse model and autopsied.
- the left lung tissue of the mouse was fixed in 10% neutral formalin for one day, and paraffin sections were made. In order to remove the paraffin around the tissue, it was reacted with xylene, 95, 90, and 70% ethanol solutions for 5 minutes each in order. Then, for trichrome staining, reaction was sequentially performed in Bouin's solution for 1 minute, Weigert's hematoxylin for 10 minutes, Phosphotunstic/phosphomolydic acid for 10 minutes, aniline blue for 5 minutes, and 1% acetic acid for 1 minute.
- the compound of Formula 1 significantly inhibits collagen deposition, which is a primary evaluation index of pulmonary fibrosis, and in particular, when administered in combination with nintedanib, the effect was confirmed to be superior to that of nintedanib alone.
Abstract
Description
시험군 | 시험물질 | 1회 투여량 | 투여경로 | 투여횟수 |
G1 | Vehicle | - | 경구 | 1일 2회, 14일간 |
G2 | Nintedanib | 30 mg/kg | 경구 | 1일 2회, 14일간 |
G3 | 화학식 1 화합물 | 10 mg/kg | 경구 | 1일 2회, 14일간 |
G4 | 화학식 1 화합물 + nintedanib |
10 + 30 mg/kg | 경구 | 1일 2회, 14일간 |
시험군 | 시험물질 | 1회 투여량 | 투여경로 | 투여횟수 |
G1 | Vehicle (정상군) | - | 경구 | 1일 2회, 14일간 |
G2 | Vehicle (유발군) | - | 경구 | 1일 2회, 14일간 |
G3 | 화학식 1 화합물 | 30 mg/kg | 경구 | 1일 2회, 14일간 |
G4 | 화학식 1 화합물 | 100 mg/kg | 경구 | 1일 2회, 14일간 |
G5 | 화학식 1 화합물 | 200 mg/kg | 경구 | 1일 2회, 14일간 |
G6 | 화학식 1 화합물+ nintedanib | 60 + 30 mg/kg | 경구 | 1일 2회, 14일간 |
G7 | Nintedanib | 60 mg/kg | 경구 | 1일 2회, 14일간 |
Claims (8)
- 제1항에 있어서, 상기 폐섬유화증은 약물요법 또는 방사선 피폭에 의해 유발된 것인, 약학 제제.
- 제1항에 있어서, 상기 폐섬유화증은 특발성 폐섬유증(Idiopathic pulmonary fibrosis)인, 약학 제제.
- 제1항 내지 제3항 중 어느 한 항에 있어서, 상기 제제는 유효 성분으로 Nintedanib 또는 이의 약학적으로 허용 가능한 염을 추가로 포함하는, 약학 제제.
- 제5항에 있어서, 상기 폐섬유화증은 약물요법 또는 방사선 피폭에 의해 유발된 것인, 방법.
- 제6항에 있어서, 상기 폐섬유화증은 특발성 폐섬유증(Idiopathic pulmonary fibrosis)인, 방법.
- 제5항 내지 제7항 중 어느 한 항에 있어서, 상기 방법은 Nintedanib 또는 이의 약학적으로 허용 가능한 염의 치료적으로 또는 예방학적으로 유효한 양을 개체에게 투여하는 것을 추가로 포함하는, 방법.
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EP22816449.7A EP4349341A1 (en) | 2021-06-01 | 2022-05-31 | Pharmaceutical preparation for preventing or treating pulmonary fibrosis |
CN202280038937.0A CN117412751A (zh) | 2021-06-01 | 2022-05-31 | 用于预防或治疗肺纤维化的药物制剂 |
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WO2020022708A1 (ko) | 2018-07-23 | 2020-01-30 | 제이투에이치바이오텍 주식회사 | 비알콜성 지방간염의 예방 또는 치료용 약학 조성물 |
KR20210071130A (ko) | 2019-12-05 | 2021-06-16 | 삼성전자주식회사 | 컴퓨팅 장치, 컴퓨팅 장치의 동작 방법, 그리고 저장 매체 |
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- 2022-05-31 WO PCT/KR2022/007778 patent/WO2022255790A1/ko active Application Filing
- 2022-05-31 KR KR1020220067106A patent/KR20220163289A/ko unknown
- 2022-05-31 EP EP22816449.7A patent/EP4349341A1/en active Pending
- 2022-05-31 CN CN202280038937.0A patent/CN117412751A/zh active Pending
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