WO2015064898A1 - 질레우톤 크림 제형의 국소용 항염증 약학적 조성물 - Google Patents
질레우톤 크림 제형의 국소용 항염증 약학적 조성물 Download PDFInfo
- Publication number
- WO2015064898A1 WO2015064898A1 PCT/KR2014/007525 KR2014007525W WO2015064898A1 WO 2015064898 A1 WO2015064898 A1 WO 2015064898A1 KR 2014007525 W KR2014007525 W KR 2014007525W WO 2015064898 A1 WO2015064898 A1 WO 2015064898A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- weight
- weight percent
- pharmaceutical composition
- cream
- cream formulation
- Prior art date
Links
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
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
-
- 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
-
- 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
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
-
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- 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
-
- 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
-
- 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
- A61P17/06—Antipsoriatics
-
- 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
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
Definitions
- the present invention relates to a zileuton cream formulation for topical treatment of skin diseases caused by leukotrin.
- Leukotrin is a metabolite of arachidonic acid and is known as an inflammatory factor deeply involved in inflammation, edema, mucus secretion, and the like.
- the leukotrin inhibitors thus far developed are Zileuton (( ⁇ ) -1- (1- (benzo [b] thiophen-2-yl) ethyl) -1-hydroxyurea).
- An object of the present invention is a disease caused by a local skin inflammatory response, such as atopic dermatitis, acne.
- a local skin inflammatory response such as atopic dermatitis, acne.
- the present invention provides a topical pharmaceutical composition of a cream formulation and a method for preparing the same, which maximize the pharmacological effect by minimizing systemic absorption by minimizing systemic absorption by topically applying ileuton to skin lesions of cytopathy. .
- the present invention provides an active ingredient, zileuton 0.05 to 2% by weight; 30 to 34 weight percent water; 36 to 40 wt% white petrolatum; Pewter 4 to 8% by weight; Propylene glycol 16-22 wt%; 2 to 6 weight percent of phosphoricone 90H; And 0.005 to 0.04 wt% of a preservative.
- the topical pharmaceutical composition of the cream formulation is more specifically, the topical pharmaceutical composition of the cream formulation is 0.1 to 1% by weight of ileuton; 31 to 33 weight percent water; 37 to 39 weight percent of white petrolatum; Pewter 5-7 wt%; Propylene glycol 18-20 wt%; 3 to 5 weight percent of phosphoricone 90H; And 0.01 to 0.03% by weight of a preservative.
- Topical pharmaceutical compositions of the cream formulations are atopic dermatitis, acne.
- the topical pharmaceutical composition of the cream formulation may be for topical application to the skin of the human body, the zileuton may be racemic zileuton.
- the present invention also relates to an active ingredient, 0.05 to 2% by weight of ileuton; 30 to 34 weight percent water; 36 to 40 wt% white petrolatum; Pewter 4 to 8% by weight; Propylene glycol 16-22 wt%; 2 to 6 weight percent of phosphoricone 90H; And 0.005 to 0.04% by weight of a preservative at a temperature of 30 to 80 ° C., 600 to 1200 rpm, and a stirring condition of 10 to 60 minutes to provide a method for preparing a topical pharmaceutical composition of a cream formulation.
- an active ingredient 0.05 to 2% by weight of ileuton; 30 to 34 weight percent water; 36 to 40 wt% white petrolatum; Pewter 4 to 8% by weight; Propylene glycol 16-22 wt%; 2 to 6 weight percent of phosphoricone 90H; And 0.005 to 0.04% by weight of a preservative at a temperature of 30 to 80 ° C., 600 to 1200 r
- the method for preparing a topical pharmaceutical composition of the cream formulation may further include cooling the mixed active ingredient at 20 to 30 ° C. at 600 rpm or less, and the zileuton may be racemic zileuton.
- the present invention is atopic dermatitis, acne (acne).
- Various types of urticaria, psoriasis, eczema, bullous pemphigoid, bullous skin diseases, collagenoses, Sjogren-Larsson syndrome, obesity There is an effect of providing a topical pharmaceutical composition in the form of a cream containing as a main component Gilleston showing an effective therapeutic effect on skin lesions of cytopathy (mastocytosis).
- the topical pharmaceutical composition in cream form has a pharmacokinetic profile that effectively absorbs leukotrin inhibitor zileuton into the skin, while minimizing systemic absorption, and possesses chemical and physical stability.
- 1 is an experimental schematic diagram verifying the efficacy of the topical application of the formulation according to the present invention to an atopic mouse model.
- 2 is the thickness of the mouse ear measured by topical application of the formulation according to the invention to an atopy mouse model.
- 3 and 4 show the results of pharmacokinetic profile studies of the formulations according to the invention in mini pigs.
- the present inventors search for components that can be applied to zileuton among the components used in the cream formulation.
- the present invention was completed by finding the cream composition of the present invention and then identifying stabilization conditions capable of realizing the optimum concentration of zileuton and physicochemical stability.
- the present invention provides an active ingredient comprising 0.05 to 2% by weight of ileuton; 30 to 34 weight percent water; 36 to 40 wt% white petrolatum; Pewter 4 to 8% by weight; Propylene glycol 16-22 wt%; 2 to 6 weight percent of phosphoricone 90H; And 0.005 to 0.04 wt% of a preservative.
- the topical pharmaceutical composition of the cream formulation is more specifically, the topical pharmaceutical composition of the cream formulation is 0.1 to 1% by weight of ileuton; 31 to 33 weight percent water; 37 to 39 weight percent of white petrolatum; Pewter 5-7 wt%; Propylene glycol 18-20 wt%; 3 to 5 weight percent of phosphoricone 90H; And 0.01 to 0.03% by weight of a preservative.
- the topical pharmaceutical composition of the cream formulation is 0.1 to 1% by weight of zileuton; 32 weight percent water; White petrolatum 38%; Pewter 6% by weight; Propylene glycol 18-20 wt%; 4% by weight of phosphoricone 90H; And 0.02% by weight of a preservative.
- Gilleutone in the present invention is (R) -1- (1- (benzo [b] thiophen-2-yl) ethyl) -1-hydroxyure and (S) -1- (1) A mixture of-(benzo [b] thiophen-2-yl) ethyl) -1-hydroxyurea in the form of a white powder, which may be racemic zileuton. That is, the present invention is to prepare a cream formulation with the active ingredient optimized for racemic zileuton.
- the zileuton may be chemically synthesized or commercially available (trade names ZYFLO, ZYFLO CR, etc., of Cornerstone Therapeutics Inc.).
- White petrolatum, white wax, propylene glycol and phospholipon 90H used in topical pharmaceutical compositions of the cream formulations of the present invention are commercially available.
- Methyl paraben, ethyl paraben, propyl paraben, isobutyl paraben, butyl paraben, 2-phenoxy ethanol, or 4-hydroxybenzoic acid may be used as the preservative, but is not particularly limited thereto. Such preservatives are also commercially available.
- Topical pharmaceutical compositions of the cream formulations according to the invention are characterized in that the physical and chemical stability is maintained for 4 weeks under conditions of 25 to 40 °C.
- the topical pharmaceutical composition of the cream formulation according to the invention has been tested for efficacy in an atopic experimental animal model (Delayed Type Hypersensitivity Reaction in mouse).
- DNFB was used to induce atopic dermatitis, applied to mouse skin three times a day, and drug efficacy was measured.
- Excess drug was administered using acetone, an unoptimized test vehicle.
- the topical pharmaceutical composition of the cream formulation may exhibit an anti-inflammatory effect through inhibiting leukotriene formation, such as atopic dermatitis, acne.
- leukotriene formation such as atopic dermatitis, acne.
- the acne may be an inflammatory acne selected from the group consisting of acne papulosa, acne pustulosa, acne papulopustolosa and severe inflammatory acne.
- the topical pharmaceutical composition of the cream formulation may be for topical application to the skin of the human body. Specifically, it may be to perform the topical application once to four times on a daily basis.
- the present invention also relates to an active ingredient, 0.05 to 2% by weight of ileuton; 30 to 34 weight percent water; 36 to 40 wt% white petrolatum; Pewter 4 to 8% by weight; Propylene glycol 16-22 wt%; 2 to 6 weight percent of phosphoricone 90H; And 0.005 to 0.04% by weight of a preservative at a temperature of 30 to 80 ° C., 600 to 1200 rpm, and agitation conditions of 10 to 60 minutes.
- the preparation method of the topical pharmaceutical composition of the cream formulation is more specifically, 0.1 to 1% by weight of ileuton; 31 to 33 weight percent water; 37 to 39 weight percent of white petrolatum; Pewter 5-7 wt%; Propylene glycol 18-20 wt%; 3 to 5 weight percent of phosphoricone 90H; And 0.01 to 0.03% by weight of a preservative.
- the preparation method of the topical pharmaceutical composition of the cream formulation is most specifically, 0.1 to 1% by weight of ileuton; 32 weight percent water; White petrolatum 38%; Pewter 6% by weight; Propylene glycol 18-20 wt%; 4% by weight of phosphoricone 90H; And 0.02% by weight of a preservative.
- the method for preparing a topical pharmaceutical composition of the cream formulation may further comprise cooling the mixed active ingredient at 20 to 30 ° C. at 600 rpm or less.
- Cream formulations prepared through the above steps can maintain stability for 4 weeks at 25 to 40 °C, may be suitable for topical application.
- the solution stability test screened for compatibility with solvents that solubilize gilleutone (ethanol, PEG400, propylene glycol, hexylene glycol, capriol 90, benzyl alcohol, water).
- solvents that solubilize gilleutone ethanol, PEG400, propylene glycol, hexylene glycol, capriol 90, benzyl alcohol, water.
- 10 mg of zileuton was dissolved in 2 mL of vehicle, and TRS% change was observed at 25 ° C, 40 ° C, and 70 ° C.
- Tables 2 and 3 below show the stability test results of the solution at 25 ° C.
- Table 3 below shows the stability test results of the solution at 40 ° C. or 70 ° C.
- composition ratios which were judged to be suitable in the suitability screening experiment were combined to screen the composition ratios of the solvent and cream formulation components stable under accelerated conditions (30 ° C., 40 ° C.).
- composition ratio having a suitable cream shape such as 022-4, 023-5, 028-5, 028-6, 028-7, 029-12, 029-14 was found. From the above results, it was confirmed that the content ratio between water, white petrolatum, pewter, and propylene glycol had critical significance within the range.
- the conditions for satisfying the target drug concentration (1%) and physical and chemical stability were screened.
- the remaining components except for solvents such as propylene glycol, water, etc. are mixed at 70 ° C. according to the composition ratio shown in Table 5 below, and then the remaining solvents are mixed at 800 rpm or lower under 70 ° C. with reference to the mixing conditions shown in Table 5 below. It was.
- the mixed formulation was cooled to room temperature with stirring below 100 rpm.
- the formulations do not contain ethanol because ethanol inhibits physical stability.
- the 036-1 and 040-1 formulations had lower physical stability but higher chemical stability.
- formulations with lower drug loadings were prepared to improve physical stability after scale up.
- the 062-1 formulation was selected and based on this formulation, the drug loading was improved by up to 1%, and the solvent was screened to ensure chemical stability while maintaining physical stability.
- the remaining components except for solvents such as propylene glycol, water, etc. were mixed under 70 ° C. according to the composition ratios shown in Table 7 below, and the remaining solvents were stirred at 800 rpm or less for 30 minutes at 70 ° C. It mixed according to a composition ratio.
- the mixed formulation was cooled to room temperature with stirring up to 100 rpm.
- NMP and benzyl alcohol were screened as a solvent, but both showed phase separation under physical stability conditions.
- capryol90 was screened as a solvent, but all showed phase separation under physical stability test conditions.
- the formulation was changed at 062-1 to increase the drug loading to 1% and found a cream formulation that satisfied both the target drug concentration and physical stability.
- the chemical stability was observed a significant TRS% change after 3 weeks at 40 °C.
- the propylene glycol content was optimized and propyleneparaben was added as a preservative.
- the cream formulations, 089-1, and 089-2 formulations of the composition ratios according to Table 10 below satisfied chemical / physical stability at 30 ° C acceleration conditions.
- the cream formulation having a composition ratio of the following Table 11 used as a comparative example was confirmed that the chemical / physical stability is not good at 30 °C acceleration conditions in the range of the target drug concentration showing an effective effect.
- mice were divided into four groups with 10 mice per group.
- the group consisted of vehicle (acetone), positive control (dexamethasone 0.05 mg / ear), zileuton group.
- the zileuton group was divided into vehicle with acetone (1 mg / ear) and with 089 cream formulation (0.2 mg / ear and 0.02 mg / ear).
- DNFB dinitrofluorobenzene
- the group using vehicle 089 formulation effectively delivered Q301 (Active Pharmaceutical Ingredient) to the skin, effectively inhibiting the increase in ear thickness due to inflammation and edema than the group using acetone.
- Q301 Active Pharmaceutical Ingredient
- Table 13 group Number of Bamma Pig Treatment (#/gender) Experimental drugs Dose (mg / cm 2) Concentration (mg API / g cream) Vehicle root Sample acquisition type One 6 males Gilleston (Q301) 0.2 (API) 10 089-1 Topical administration Plasma, skin Drug storage: dried at 4 ° C Animals in the 15 to 20kg body weight range are used, and the dosage range is 10cm X 10cm Overnight Fast of Animals: None
- the 089 formulation showed an effective skin absorption pattern.
- the 089 formulation showed no absorption pattern in mini pigs.
- the cream formulation using propylene glycol effectively induces skin absorption and minimizes the absorption in the body, thus making it suitable as a candidate formulation of zileuton for future skin administration.
- the present invention is to provide a zileuton cream formulation for topical treatment of skin diseases caused by leukotrin, which is an industrially available invention.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Pulmonology (AREA)
- Transplantation (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
Abstract
Description
No. | 부형제 | API:부형제 비율 | 0일 | 2주, 50℃ | 4주, 50℃ | ||||||
형태 | 회복율% | TRS.% | 형태 | 회복율% | TRS.% | 형태 | 회복율% | TRS.% | |||
1 | 질레우톤(Q301) | API | - | - | 2.378 | 백색파우더 | 101.47 | 3.311 | 백색파우더 | 99.12 | 2.711 |
101.30 | 3.006 | 98.23 | 2.493 | ||||||||
2 | 스테아릴알코올(Stearyl Alcohol) | 1:1 | 백색파우더 | 98.71 | 3.311 | 백색파우더 | 101.69 | 2.935 | 백색파우더 | 102.91 | 2.512 |
101.28 | 2.796 | 98.77 | 2.567 | ||||||||
3 | 세테아레스-20(Ceteareth-20) | 1:1 | 백색파우더 | 100.34 | 2.394 | 백색파우더 | 99.99 | 3.445 | 백색반고체 | 97.59 | 3.632 |
100.36 | 3.365 | 96.39 | 3.549 | ||||||||
4 | 포스포리폰 90H | 1:1 | 백색파우더 | 100.61 | 2.400 | 백색파우더 | 101.50 | 2.820 | 백색파우더 | 97.26 | 2.557 |
102.21 | 2.846 | 103.30 | 2.429 | ||||||||
5 | 백랍 | 1:1 | 백색파우더 | 99.46 | 2.372 | 백색파우더 | 100.70 | 2.863 | 백색파우더 | 98.77 | 2.459 |
102.20 | 2.843 | 97.31 | 2.381 | ||||||||
6 | 이산화티타늄 | 1:1 | 백색파우더 | 100.59 | 2.344 | 백색파우더 | 102.55 | 2.803 | 백색파우더 | 99.14 | 2.507 |
102.86 | 2.839 | 99.17 | 2.504 | ||||||||
7 | 하이프로멜로스(HPMC) | 1:1 | 백색파우더 | 103.72 | 2.610 | 백색파우더 | 102.67 | 2.864 | 백색파우더 | 98.86 | 2.555 |
102.97 | 2.949 | 100.86 | 2.580 | ||||||||
8 | 카보머(Carbomer) | 1:1 | 백색파우더 | 99.34 | 3.326 | 백색파우더 | 102.45 | 2.385 | 백색파우더 | 99.63 | 2.330 |
103.39 | 3.067 | 97.65 | 2.403 |
용매 | 온도 | TRS (%) | TRS 증가율 % | |||
0일 | 1일 | 3일 | 8일 | |||
에탄올 | 25℃ | 1.255 | 1.014 | 1.951 | 2.137 | 0.882 |
폴리에틸렌글리콜(PEG- 400) | 25℃ | 1.427 | 1.491 | 2.897 | 4.065 | 2.638 |
프로필렌 글리콜 | 25℃ | 1.457 | 1.624 | 1.478 | 2.132 | 0.675 |
헥실렌 글리콜 | 25℃ | 1.505 | 1.448 | 1.583 | 1.980 | 0.475 |
카프리올 90 | 25℃ | 1.623 | 1.444 | 1.478 | 2.201 | 0.578 |
벤질 알코올 | 25℃ | 1.642 | 0.869 | 1.806 | 2.023 | 0.381 |
물 | 25℃ | 1.424 | 1.879 | 1.816 | 1.965 | 0.541 |
용매 | 온도 | TRS (%) | TRS 증가율 % | |||
0일 | 1일 | 3일 | 8일 | |||
에탄올 | 40℃ | 1.255 | 1.778 | 2.375 | 4.704 | 3.449 |
폴리에틸렌글리콜(PEG- 400) | 70℃ | 1.427 | 43.725 | 94.366 | 97.142 | 95.715 |
프로필렌 글리콜 | 70℃ | 1.457 | 26.382 | 82.228 | 96.325 | 94.868 |
헥실렌 글리콜 | 70℃ | 1.505 | 8.061 | 29.999 | 60.352 | 58.847 |
카프리올 90 | 70℃ | 1.623 | 10.312 | 39.603 | 76.445 | 74.822 |
벤질 알코올 | 70℃ | 1.642 | 11.350 | 20.397 | 24.250 | 22.608 |
물 | 70℃ | 1.424 | 35.171 | 80.268 | 91.994 | 90.570 |
구성성분(%) | 022-1 | 022-4 | 023-5 | 023-7 | 029-10 | 028-1 | 028-2 | 028-5 | 028-6 | 028-7 | 029-12 | 029-14 |
질레우톤(Q301) | - | - | - | - | - | - | - | - | - | - | - | - |
물 | - | - | - | 57 | 16 | - | - | 10~31 | ||||
백색 바세린 | 43 | 38~48 | 24 | 20 | 43 | 38 | 18~31 | |||||
백랍 | 6 | 6 | 6 | 6 | 5 | 7 | 7 | 5~9 | ||||
프로필렌 글리콜(PG) | 24 | 32~42 | 10 | 55 | 47 | 52 | 25~55 | |||||
스테아릴알코올(Stearyl Alcohol) | 16 | - | - | - | - | - | - | - | - | - | - | - |
프로필렌 글리콜 스테아르산염 | - | - | - | - | - | - | - | - | - | - | - | - |
포스포리폰 90H | - | 3 | 3 | 3 | 4 | 3 | 3 | 4 | 4 | 4 | 4 | 4 |
에탄올 | - | - | - | - | - | - | - | - | - | - | 10.5 | 10.5 |
알루미늄스타치옥테닐썩시네이트 | 11 | 11 | 11 | - | - | - | - | - | - | - | - | - |
형태 | Littledrycream | Cream | Cream | Liquid | Oint. | Oilycream | Very oilycream | Cream | Cream | Cream | Cream | Cream |
근사 용해성 (%) | - | - | - | - | <1.3% | <3% | - | <0.1% | <0.3% | <0.7% | <2.3% | <2.5% |
구성성분(%) | 030-1 | 030-2 | 030-3 | 030-4 | 032-4 | 033-1 | 033-2 | 033-3 | 033-4 | 033-5 | 033-6 | 033-7 |
질레우톤(Q301) | - | - | - | - | - | - | - | - | - | - | - | - |
물 | 10~12 | 17~21 | ||||||||||
백색 바세린 | 18~20 | 17~21 | ||||||||||
백랍 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 |
프로필렌 글리콜(PG) | 51 | 51 | 53 | 55 | 55 | 51 | 54 | 51 | 48 | 52 | 54 | 56 |
포스포리폰 90H | 4 | 4 | 4 | 4 | 4 | 5 | 5 | 4 | 4 | 4 | 4 | 4 |
에탄올 | 4.5~9 | - | - | - | - | |||||||
교반시간(분) | 20 | 20 | 20 | 20 | 20 | 20 | 20 | 20 | 20 | 20 | 20 | 20 |
형태 | Cream | Cream | Cream | Cream | Cream | Cream | Cream | Cream | Cream | Cream | Cream | Cream |
근사 용해성 (%) | <2.1% | <1.8% | <2.7% | <2.7% | <2.3% | <2.1% | <2.1% | <2.1% | <1.3% | <1.5% | <1.7% | <2.1% |
25℃에서의 물리적 안정성 | Bad | Bad | Bad | Bad | Bad | Bad | Bad | Bad | Good | Good | Good | Good |
구성성분(%) | 031-1 | 062-1 | 037-1 |
질레우톤(Q301) | - | - | - |
물 | 10~26 | ||
백색 바세린 | 17~29 | ||
백랍 | 6 | 6 | 6 |
프로필렌 글리콜(PG) | 35~56 | ||
포스포리폰 90H | 4 | 4 | 4 |
에탄올 | 6.5 | - | - |
구성성분의 총합 | 100 | 100 | 100 |
교반시간(분) | 5 | 30 | 60 |
형태 | Liquid like Cream | Cream | Cream |
근사 용해성 (%) | - | 0.3% | <1.3% |
30℃에서의 물리적 안정성 | Good |
구성성분(%) | 엔메틸피롤리돈(NMP) | 카프리올 90 | 벤질 알코올 | |||||||
064-1 | 066-1 | 067-1 | 078-2 | 080-1 | 080-2 | 073-4 | 073-5 | 073-6 | 073-7 | |
질레우톤(Q301) | - | - | - | - | - | - | - | - | - | - |
물 | 24~26 | 20~24 | 37~41 | |||||||
백색 바세린 | 29~33 | 29~33 | 38~42 | |||||||
백랍 | 6 | 6 | 6 | 12~24 | 6 | |||||
프로필렌 글리콜(PG) | 24 | 24 | 24 | - | - | - | - | - | - | - |
스테아릴알코올(Stearyl Alcohol) | - | - | - | - | - | - | 4 | - | - | - |
프로필렌 글리콜 스테아르산염 | - | - | - | - | - | - | - | 4 | - | - |
포스포리폰 90H | 4 | 4 | 4 | 4 | 4 | 4 | - | - | 4 | 4 |
에탄올 | - | - | - | - | - | - | - | - | - | - |
알루미늄스타치옥테닐썩시네이트 | - | - | - | - | - | - | - | - | - | - |
엔메틸피롤리돈(NMP) | 10 | 10 | 8 | - | - | - | - | - | - | - |
벤질 알코올 | - | - | - | - | - | - | 14 | 14 | 10 | 10 |
카프리올 90 | - | - | - | 28 | 28 | 28 | - | - | - | - |
다이메틸설폭사이드 | - | - | - | - | - | - | - | - | - | - |
교반시간(분) | 30 | 30 | 30 | 30 | 30 | 30 | 30 | 30 | 30 | 30 |
형태 | Liquid | Liquid | Cream | Cream | Cream | Cream | Cream | Cream | Cream | Cream |
근사 용해성 (%) | 1% | 1% | 0.8% | 0.8% | 0.8% | 0.8% | ||||
30℃에서의 물리적 안정성 | Bad | |||||||||
40℃에서의 물리적 안정성 | Bad | Bad | Bad | Bad | Bad | Bad | Bad |
구성성분(%) | 기준(Criteria) | 079-1 | 083-1 |
질레우톤(Q301) | - | - | - |
물 | 30~40 | 32 | 32 |
백색 바세린 | 36~40 | 33 | 38 |
백랍 | 4~8 | 6 | 6 |
프로필렌 글리콜(PG) | 16~22 | 25 | 19 |
포스포리폰 90H | 2~6 | 4 | 4 |
형태 | Cream | Cream | Cream |
40℃하에서 4주간의 물리적 안정성 | 안정함 | 4주째 상분리 관찰됨 | 안정함 |
후보 제형 | ||
구성성분 (%) | 081-1 | 081-2 |
질레우톤 (Q301) | 1 | 1 |
물 | 32 | 26 |
백색 바세린 | 32 | 29 |
백랍 | 6 | 6 |
프로필렌 글리콜(PG) | 25 | 34 |
포스포리폰 90H | 4 | 4 |
구성성분의 총합 | 100 | 100 |
교반시간 (분) | 30 | 30 |
형태 | Cream | Cream |
근사 용해성 (%) | 1% | 1% |
40℃에서의 물리적 안정성 | Good | Good |
40℃에서의 화학적 안정성 (TRS %) | 3주간 6.65% 변화 | 3주간 9.79% 변화 |
크림제형 성분 | 089-1 (중량%) | 089-2 (중량%) |
Q301 (질레우톤) | 0.1 | 1 |
물 | 32 | 32 |
백색 바셀린 (White Petrolatum) | 38 | 38 |
백랍 (White Wax) | 6 | 6 |
프로필렌 글리콜 (Propylene Glycol) | 19.88 | 18.98 |
포스포리폰 90H (Phospholipon 90H) | 4 | 4 |
보존제 (Propylparaben) | 0.02 | 0.02 |
구성성분 총합 | 100 | 100 |
교반시간 (분) | 30 | 30 |
형태 | 크림 | 크림 |
물리적 안정성 | 4주동안 좋음 | 4주동안 좋음 |
화학적 안정성(TRS %) | 30℃에서 4주간 1.4% 변화 | 30℃에서 4주간 1.4% 변화 |
비교 크림제형 성분 | 058-1 (중량%) | 059-1 (중량%) |
Q301 (질레우톤) | 0.7 | 0.7 |
물 | 24 | 22 |
백색 바셀린 (White Petrolatum) | 25 | 27 |
백랍 (White Wax) | 3 | 3 |
프로필렌 글리콜 (Propylene Glycol) | 46 | 46 |
포스포리폰 90H (Phospholipon 90H) | 1 | 1 |
보존제 (Propylparaben) | 0.02 | 0.02 |
교반시간 (분) | 30 | 30 |
형태 | 크림 | 크림 |
물리적 안정성 | 30℃에서 층분리 관찰됨 | 30℃에서 층분리 관찰됨 |
실험모델 | BALB/c 마우스, 암컷 6~8주령 (17~20g) | ||||||
투여량(Dosing) | |||||||
그룹 | 약물(제형) | No. | 루트 | 농도 (mg/mL 또는 %) | mL 또는 mg/ear | APImg/ear | Regimen(시간) |
1 | 비히클(아세톤) | 10 | 국소 | N/A | 0.02mL | N/A | 1,6,23 |
2 | Dex(아세톤) | 10 | 국소 | 2.5mg/mL | 0.02mL | 0.05 | 1,6,23 |
3 | Q301(아세톤) | 10 | 국소 | 50mg/mL | 0.02mL | 1 | 1,6,23 |
4 | Q301(089-2제형) | 10 | 국소 | 1% | 20mg | 0.2 | 1,6,23 |
5 | Q301(089-1제형) | 10 | 국소 | 0.1% | 20mg | 0.02 | 1,6,23 |
측정 | * 체중* 귀 두께* 조직병리학적 관찰 (부종, 염증, 크러스트 형성) |
그룹 | Bamma Pig의 수 | 처치(Treatment) | |||||
(#/성별) | 실험 약물 | 투여량(mg/㎠) | 농도 (mg API/g cream) | 비히클 | 루트 | 시료수득타입 | |
1 | 숫컷 6마리 | 질레우톤(Q301) | 0.2(API) | 10 | 089-1제형 | 국소투여 | 혈장, 피부 |
약물 저장 : 4℃하에서 건조됨 | 15~20kg 체중 범위의 동물을 사용하며, 투여범위는 10cm X 10cm임 | ||||||
동물의 밤동안의 금식(Overnight Fast of Animals) : 없음 |
그룹 | 투여루트 | 동물ID | 샘플링 및 투여 스케줄 (시간) | ||||||||||
-0.5 | 0 | 0.25 | 0.5 | 1 | 1.5 | 2 | 3 | 4 | 6 | 8 | |||
1 | 국소 | 1~3 | P | D | P | 0 | P+S | - | - | - | - | - | - |
4~6 | P | D | - | P | - | P | P | P | P | P | P+S | ||
P: 혈액을 수집한 후, 혈장을 분리함D: 동물에 대해 설정된 시간에 약물을 투여함P+S: 혈액과 피부을 수득하고, 혈액에서 혈장을 분리 수득함. 피부샘플을 수득하기 전에 각질층을 수득함. 피부에서 표피와 진피를 분리함 | |||||||||||||
항음고제 : K2-EDTA |
Claims (11)
- 활성 성분으로서,질레우톤 0.05 내지 2 중량%; 물 30 내지 34 중량%; 백색 바셀린 36 내지 40 중량%; 백랍 4 내지 8 중량%; 프로필렌 글리콜 16 내지 22 중량%; 포스포리폰 90H 2 내지 6 중량%; 및 보존제 0.005 내지 0.04 중량%;를 포함하는 질레우톤 크림 제형의 국소용 항염증 약학적 조성물.
- 제1항에 있어서,상기 활성 성분은 질레우톤 0.1 내지 1 중량%; 물 31 내지 33 중량%; 백색 바셀린 37 내지 39 중량%; 백랍 5 내지 7 중량%; 프로필렌 글리콜 18 내지 20 중량%; 포스포리폰 90H 3 내지 5 중량%; 및 보존제 0.01 내지 0.03 중량%;를 포함하는 질레우톤 크림 제형의 국소용 항염증 약학적 조성물.
- 제1항에 있어서,상기 보존제는 메틸파라벤, 에틸파라벤, 프로필파라벤, 아이소뷰틸파라벤, 뷰틸 파라벤, 2-페녹시 에탄올 및 4-히드록시벤조산으로 이루어진 군으로부터 선택된 하나 이상인 질레우톤 크림 제형의 국소용 항염증 약학적 조성물.
- 제1항에 있어서,상기 조성물은 아토피성 피부염(atopic dermatitis), 여드름(acne). 두드러기(urticaria), 건선(psoriasis), 습진(eczema), 수포성 류천포창(bullous pemphigoid)과 같은 수포성 피부 질환(bullous skin diseases), 교원질증(collagenoses), Sjogren-Larsson 증후군, 또는 비만세포증(mastocytosis)의 피부 병변의 여드름 개선 또는 치료를 위한 것인 질레우톤 크림 제형의 국소용 항염증 약학적 조성물.
- 제1항에 있어서,상기 조성물은 인체의 피부에 대한 국소 도포를 위한 것인 질레우톤 크림 제형의 국소용 항염증 약학적 조성물.
- 제1항에 있어서,상기 질레우톤은 라세믹 질레우톤인 질레우톤 크림 제형의 국소용 항염증 약학적 조성물.
- 활성 성분으로서, 질레우톤 0.05 내지 2 중량%; 물 30 내지 34 중량%; 백색 바셀린 36 내지 40 중량%; 백랍 4 내지 8 중량%; 프로필렌 글리콜 16 내지 22 중량%; 포스포리폰 90H 2 내지 6 중량%; 및 보존제 0.005 내지 0.04 중량%를 30 내지 80℃의 온도, 600 내지 1200 rpm 및 10 내지 60분의 교반 조건에서 혼합하는 단계를 포함하는 질레우톤 크림 제형의 국소용 항염증 약학적 조성물의 제조방법.
- 제7항에 있어서,질레우톤 0.1 내지 1 중량%; 물 31 내지 33 중량%; 백색 바셀린 37 내지 39 중량%; 백랍 5 내지 7 중량%; 프로필렌 글리콜 18 내지 20 중량%; 포스포리폰 90H 3 내지 5 중량%; 및 보존제 0.01 내지 0.03 중량%로 혼합하는 질레우톤 크림 제형의 국소용 항염증 약학적 조성물의 제조방법.
- 제7항에 있어서,상기 보존제는 메틸파라벤, 에틸파라벤, 프로필파라벤, 아이소뷰틸파라벤, 뷰틸 파라벤, 2-페녹시 에탄올, 4-히드록시벤조산으로 이루어진 군으로부터 선택된 하나 이상인 질레우톤 크림 제형의 국소용 항염증 약학적 조성물의 제조방법.
- 제7항에 있어서,혼합된 활성 성분을 600 rpm 이하에서 20 내지 30℃에서 냉각하는 단계를 더 포함하는 질레우톤 크림 제형의 국소용 항염증 약학적 조성물의 제조방법.
- 제7항에 있어서,상기 질레우톤은 라세믹 질레우톤인 질레우톤 크림 제형의 국소용 항염증 약학적 조성물의 제조방법.
Priority Applications (15)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP14858248.9A EP3064197B1 (en) | 2013-10-30 | 2014-08-13 | Topical anti-inflammatory pharmaceutical composition with zileuton cream formulation |
CA2907060A CA2907060C (en) | 2013-10-30 | 2014-08-13 | Topical anti-inflammatory pharmaceutical composition with zileuton cream formulation |
JP2016525982A JP6159885B2 (ja) | 2013-10-30 | 2014-08-13 | ジロートンクリーム剤形の局所用抗炎症薬学的組成物 |
BR112016009777-7A BR112016009777B1 (pt) | 2013-10-30 | 2014-08-13 | Composição farmacêutica anti-inflamatória tópica com formulação de creme de zileutona |
US14/777,183 US9655841B2 (en) | 2013-10-30 | 2014-08-13 | Topical anti-inflammatory pharmaceutical composition with zileuton cream formulation |
DK14858248.9T DK3064197T3 (en) | 2013-10-30 | 2014-08-13 | TOPICAL ANTI-INFLAMMATORY PHARMACEUTICAL COMPOSITION WITH ZILEUTON - CREAM FORMULATION |
ES14858248.9T ES2688469T3 (es) | 2013-10-30 | 2014-08-13 | Composición farmacéutica antiinflamatoria tópica con formulación en crema de zileutón |
SG11201602888SA SG11201602888SA (en) | 2013-10-30 | 2014-08-13 | Topical anti-inflammatory pharmaceutical composition with zileuton cream formulation |
AU2014341014A AU2014341014B2 (en) | 2013-10-30 | 2014-08-13 | Topical anti-inflammatory pharmaceutical composition with zileuton cream formulation |
CN201480057004.1A CN105658202B (zh) | 2013-10-30 | 2014-08-13 | 齐留通乳膏剂型的局部用抗炎症药学组合物 |
RU2016114076A RU2616254C1 (ru) | 2013-10-30 | 2014-08-13 | Противовоспалительная фармацевтическая композиция для местного применения в виде крема с цилейтоном |
PH12016500726A PH12016500726A1 (en) | 2013-10-30 | 2016-04-19 | Topical anti-inflammatory pharmaceutical composition with zileuton cream formulation |
US15/215,909 US9855243B2 (en) | 2013-10-30 | 2016-07-21 | Topical anti-inflammatory pharmaceutical composition with zileuton cream formulation |
HK16111994.5A HK1223568A1 (zh) | 2013-10-30 | 2016-10-18 | 齊留通乳膏劑型的局部用抗炎症藥學組合物 |
US15/816,594 US20180092877A1 (en) | 2013-10-30 | 2017-11-17 | Topical anti-inflammatory pharmaceutical composition with zileuton cream formulation |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2013-0130165 | 2013-10-30 | ||
KR1020130130165A KR101462474B1 (ko) | 2013-10-30 | 2013-10-30 | 질레우톤 크림 제형의 국소용 항염증 약학적 조성물 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US14/777,183 A-371-Of-International US9655841B2 (en) | 2013-10-30 | 2014-08-13 | Topical anti-inflammatory pharmaceutical composition with zileuton cream formulation |
US15/215,909 Continuation-In-Part US9855243B2 (en) | 2013-10-30 | 2016-07-21 | Topical anti-inflammatory pharmaceutical composition with zileuton cream formulation |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2015064898A1 true WO2015064898A1 (ko) | 2015-05-07 |
Family
ID=52290736
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/KR2014/007525 WO2015064898A1 (ko) | 2013-10-30 | 2014-08-13 | 질레우톤 크림 제형의 국소용 항염증 약학적 조성물 |
Country Status (16)
Country | Link |
---|---|
US (1) | US9655841B2 (ko) |
EP (1) | EP3064197B1 (ko) |
JP (1) | JP6159885B2 (ko) |
KR (1) | KR101462474B1 (ko) |
CN (1) | CN105658202B (ko) |
AU (1) | AU2014341014B2 (ko) |
BR (1) | BR112016009777B1 (ko) |
CA (1) | CA2907060C (ko) |
DK (1) | DK3064197T3 (ko) |
ES (1) | ES2688469T3 (ko) |
HK (1) | HK1223568A1 (ko) |
HU (1) | HUE039408T2 (ko) |
PH (1) | PH12016500726A1 (ko) |
RU (1) | RU2616254C1 (ko) |
SG (1) | SG11201602888SA (ko) |
WO (1) | WO2015064898A1 (ko) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021121645A1 (en) | 2019-12-20 | 2021-06-24 | Qurient Co., Ltd. | A topical anti-inflammatory pharmaceutical composition comprising zileuton |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9855243B2 (en) * | 2013-10-30 | 2018-01-02 | Qurient Co., Ltd. | Topical anti-inflammatory pharmaceutical composition with zileuton cream formulation |
KR20210045987A (ko) * | 2018-08-16 | 2021-04-27 | 닥터 레디스 레보러터리즈 리미티드 | 국소적 유지성 조성물 |
KR20230080579A (ko) | 2021-11-30 | 2023-06-07 | 한국원자력의학원 | 질레우톤(zileuton)을 유효성분으로 포함하는 피부 방사선 증후군 예방 또는 치료용 약학 조성물 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20040008166A (ko) * | 2001-04-30 | 2004-01-28 | 크리스토스 초우보울리스 | 여드름 치료제 |
US20040171599A1 (en) * | 2001-04-04 | 2004-09-02 | Dorothea Ledergerber | Pharmaceutical compositions |
US8003684B2 (en) * | 2006-02-21 | 2011-08-23 | Cornerstone Therapeutics, Inc. | Crystal form and pharmaceutical compositions of (+)-R-zileuton |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050090553A1 (en) * | 1992-06-30 | 2005-04-28 | Shapiro Howard K. | Compositions and method for treatment of chronic inflammatory diseases |
EP0799051B1 (en) * | 1994-12-12 | 2005-07-27 | Omeros Corporation | Irrigation solution and use thereof for perioperatively inhibiting pain, inflammation and spasm at a wound |
US6656928B1 (en) * | 1999-09-02 | 2003-12-02 | Mccadden Michael E. | Composition for the topical treatment of rashes, dermatoses and lesions |
BRPI0618661A2 (pt) * | 2005-11-15 | 2011-09-06 | Baxter Int | composições de inibidores de lipoxigenase |
WO2008106081A1 (en) * | 2007-02-26 | 2008-09-04 | Larry Schlesinger | Topical formulations containing leukotriene receptor antagonist and use for treatment or prevention of capsular contracture, scarring or hyperpigmentation |
CN102988276B (zh) * | 2011-09-08 | 2015-09-09 | 哈药集团生物工程有限公司 | 一种盐酸特比萘芬乳膏处方及其制备工艺 |
GB201118193D0 (en) * | 2011-10-21 | 2011-12-07 | Jagotec Ag | Improvements in or relating to oranic compounds |
CN203126976U (zh) * | 2013-01-07 | 2013-08-14 | 浙江吉利汽车研究院有限公司杭州分公司 | 汽车发动机罩内板 |
-
2013
- 2013-10-30 KR KR1020130130165A patent/KR101462474B1/ko active IP Right Grant
-
2014
- 2014-08-13 AU AU2014341014A patent/AU2014341014B2/en active Active
- 2014-08-13 ES ES14858248.9T patent/ES2688469T3/es active Active
- 2014-08-13 SG SG11201602888SA patent/SG11201602888SA/en unknown
- 2014-08-13 EP EP14858248.9A patent/EP3064197B1/en active Active
- 2014-08-13 CN CN201480057004.1A patent/CN105658202B/zh active Active
- 2014-08-13 RU RU2016114076A patent/RU2616254C1/ru active
- 2014-08-13 US US14/777,183 patent/US9655841B2/en active Active
- 2014-08-13 DK DK14858248.9T patent/DK3064197T3/en active
- 2014-08-13 JP JP2016525982A patent/JP6159885B2/ja active Active
- 2014-08-13 HU HUE14858248A patent/HUE039408T2/hu unknown
- 2014-08-13 CA CA2907060A patent/CA2907060C/en active Active
- 2014-08-13 WO PCT/KR2014/007525 patent/WO2015064898A1/ko active Application Filing
- 2014-08-13 BR BR112016009777-7A patent/BR112016009777B1/pt active IP Right Grant
-
2016
- 2016-04-19 PH PH12016500726A patent/PH12016500726A1/en unknown
- 2016-10-18 HK HK16111994.5A patent/HK1223568A1/zh unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040171599A1 (en) * | 2001-04-04 | 2004-09-02 | Dorothea Ledergerber | Pharmaceutical compositions |
KR20040008166A (ko) * | 2001-04-30 | 2004-01-28 | 크리스토스 초우보울리스 | 여드름 치료제 |
US8003684B2 (en) * | 2006-02-21 | 2011-08-23 | Cornerstone Therapeutics, Inc. | Crystal form and pharmaceutical compositions of (+)-R-zileuton |
Non-Patent Citations (1)
Title |
---|
See also references of EP3064197A4 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021121645A1 (en) | 2019-12-20 | 2021-06-24 | Qurient Co., Ltd. | A topical anti-inflammatory pharmaceutical composition comprising zileuton |
Also Published As
Publication number | Publication date |
---|---|
ES2688469T3 (es) | 2018-11-02 |
PH12016500726B1 (en) | 2016-05-30 |
JP2016534079A (ja) | 2016-11-04 |
CA2907060A1 (en) | 2015-05-07 |
BR112016009777A2 (ko) | 2017-08-01 |
AU2014341014B2 (en) | 2016-12-15 |
HK1223568A1 (zh) | 2017-08-04 |
PH12016500726A1 (en) | 2016-05-30 |
AU2014341014A1 (en) | 2016-04-21 |
SG11201602888SA (en) | 2016-05-30 |
JP6159885B2 (ja) | 2017-07-05 |
EP3064197A4 (en) | 2017-04-26 |
EP3064197B1 (en) | 2018-08-08 |
CN105658202B (zh) | 2019-09-13 |
DK3064197T3 (en) | 2018-10-08 |
KR101462474B1 (ko) | 2014-11-19 |
CA2907060C (en) | 2020-08-25 |
EP3064197A1 (en) | 2016-09-07 |
US20160228353A1 (en) | 2016-08-11 |
CN105658202A (zh) | 2016-06-08 |
RU2616254C1 (ru) | 2017-04-13 |
US9655841B2 (en) | 2017-05-23 |
HUE039408T2 (hu) | 2018-12-28 |
BR112016009777B1 (pt) | 2023-02-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2015064898A1 (ko) | 질레우톤 크림 제형의 국소용 항염증 약학적 조성물 | |
JP2002537243A (ja) | ホスホコリン結合プロドラッグ誘導体 | |
AU2007341218A1 (en) | Isosorbide mononitrate derivatives for the treatment of intestinal disorders | |
US20180092877A1 (en) | Topical anti-inflammatory pharmaceutical composition with zileuton cream formulation | |
WO2019245309A1 (en) | A sustained release pharmaceutical preparation comprising tacrolimus | |
EP4249476A1 (en) | Salt of benzothiazole compound, and crystal form and use thereof | |
EP2158908A1 (en) | Composition for transdermal or transmucosal administration | |
CN114929682B (zh) | 苯并硫代吡喃酮类化合物的盐及其制备方法和用途 | |
JP2003512425A (ja) | 6−メトキシ−2−ナフチル酢酸プロドラッグ | |
JP2023508844A (ja) | 左旋性二環式モルホリン及びその塩、その調製方法、医薬組成物、並びに使用 | |
WO2019124789A1 (ko) | 이리노테칸 또는 그의 약제학적으로 허용가능한 염을 포함하는 경구투여용 약제학적 조성물 | |
EP3901141B1 (en) | Novel form of isoquinoline sulfonamide | |
EP3085698B1 (en) | Pain-related compound and medicinal composition | |
WO2024029639A1 (ko) | 3성분 프로드럭, 이의 약학적 조성물 및 의약 용도 | |
RU2819002C1 (ru) | Левовращающий бициклический морфолин и его соль, способ его получения, его фармацевтическая композиция и применение | |
EP1142575B1 (en) | Dry skin remedies | |
KR102552315B1 (ko) | 펠루비프로펜 신규 염을 주성분으로 하며 위장장애 부작용이 저감된 약학적 조성물 | |
WO2011013992A2 (en) | R-7-(3-aminomethyl-4-methoxyimino-3-methyl-pyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid and l-aspartic acid salt, process for the preparation thereof and pharmaceutical composition comprising the same for antimicrobial | |
EP4092028A1 (en) | Crystal of hypoxanthine compound | |
CN115894283A (zh) | 一种曲尼司特衍生物及其制备方法和用途 | |
WO2020138935A1 (ko) | 근이영양증의 치료 또는 예방에 유용한 화합물 및 이들의 의약 용도의 치료, 개선 또는 예방용 유도체 | |
WO2023121232A1 (ko) | 용해도가 개선된 풀베스트란트의 약학 조성물 및 그 제조 방법 |
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: 14858248 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2907060 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 14777183 Country of ref document: US |
|
REEP | Request for entry into the european phase |
Ref document number: 2014858248 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2014858248 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 12016500726 Country of ref document: PH |
|
ENP | Entry into the national phase |
Ref document number: 2016525982 Country of ref document: JP Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: 2014341014 Country of ref document: AU Date of ref document: 20140813 Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: IDP00201602950 Country of ref document: ID |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
REG | Reference to national code |
Ref country code: BR Ref legal event code: B01A Ref document number: 112016009777 Country of ref document: BR |
|
ENP | Entry into the national phase |
Ref document number: 2016114076 Country of ref document: RU Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: 112016009777 Country of ref document: BR Kind code of ref document: A2 Effective date: 20160429 |