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WO2008048018A1 - Suspension d'un matériau à base de megestrol pharmaceutiquement stable - Google Patents

Suspension d'un matériau à base de megestrol pharmaceutiquement stable Download PDF

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Publication number
WO2008048018A1
WO2008048018A1 PCT/KR2007/004972 KR2007004972W WO2008048018A1 WO 2008048018 A1 WO2008048018 A1 WO 2008048018A1 KR 2007004972 W KR2007004972 W KR 2007004972W WO 2008048018 A1 WO2008048018 A1 WO 2008048018A1
Authority
WO
WIPO (PCT)
Prior art keywords
suspension
daim
agent
suspension according
viscosity
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/KR2007/004972
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English (en)
Inventor
Sang Wook Kim
Suk Kyoon Yoon
Mi Hong Min
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
LG Chem Ltd
Original Assignee
LG Life Sciences Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by LG Life Sciences Ltd filed Critical LG Life Sciences Ltd
Priority to CN2007800430440A priority Critical patent/CN101553208B/zh
Publication of WO2008048018A1 publication Critical patent/WO2008048018A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • 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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers

Definitions

  • the present invention relates to a suspension of megestrol material which is physically stable under room temperature, accelerated conditions and severe conditions, and a pharmaceutical composition thereof.
  • Megestrol acetate is a generic name of 17 ⁇ -acetoxy-6-methyl-4,6- pregnadiene-
  • Megestrol acetate is an anti-tumor agent used for relief therapy in advanced breast cancer and endometrial cancer, and is used for the purpose of treating inappetence, cachexia or noticeable weight bss of unknown origin in cancer or AIDS patients.
  • Megestrol acetate is currently on sale in the market in forms of tablet (LG Megestrol Tab.: LG life Science, Co. Ltd.) or suspension (Megace Suspension: Bristol-Myers Squibb).
  • a pharmaceutical dosage form of liquid phase is preferable when a patient has a trouble in swallowing tablet or capsule, or is required to intake a relatively large amount of tablets due to a high dosage.
  • the devebpment of a suspension of megestrol acetate has an important meaning.
  • suspension it is important to maintain a stable form without physical/chemical deterioration during the period of circulation.
  • Che of the factors to be considered mostly in evaluating the stability of a suspension is sedimentation of components in the suspension and redispersibility thereof.
  • Korean Patent No. 0211192 by Bristol-Myers Squibb Company suggests a measurement of sedimentation height as a general method for evaluating the stability of a suspension.
  • a sedimentation ratio of flocculated suspension is determined by measuring the height of sedimentation periodically with using cylinder.
  • the Korean Patent No. 0211192 by Bristol-Myers Squibb Company provides a pharmaceutical composition of megestrol acetate suspension which is not de- flocculated during the preservation period of the product.
  • This pharmaceutical composition consists of micronized megestrol acetate in combination with polysorbate 80 and poly ethylenegly col 1450, xanthan gum, sodium benzoate, citric acid, sodium citrate, sucrose, flavoring agent, and water.
  • the suspension in this patent is very viscous, and thus the time to remain in mouth and tube when orally administered is long. As a result, the drug's bss amount becomes large, causing inconvenience to patients in oral administration.
  • US Patent No. 6,028,055 mentions a flocculated oral suspension of micronized megestrol acetate which is stable in water.
  • a suspension comprising at least one component selected from the group consisting of polyethyleneglycol, propylene glycol, glycerol and sorbitol; surfactant; and megestrol acetate, particularly indicating that polysorbate as a surfactant is not used with polyethyleneglycol simultaneously.
  • the object of the present invention is to provide a low viscous suspension wherein megestrol material, which is a very hydrophobic active ingredient, is wetted effectively in water and maintains bng-term homogeneous dispersion state (i.e. high sedimentation ratio) in spite of the bw viscosity.
  • the present invention relates to a suspension comprising a megestrol material as active ingredient, a pofoxamer as wetting agent, and a viscosity controlling agent.
  • Figure 1 is a graph representing sedimentation ratios at room temperature in
  • Figure 2 is a graph representing sedimentation ratios under 4O 0 C and 75%RH condition in Comparative Example and Example 6.
  • Figure 3 is a graph representing sedimentation ratios in 6O 0 C drying oven in
  • Figure 5 is a graph representing dissolution patterns in Examples 1, 2, 5, 6 and 9.
  • megestrol material used as active ingredient means megestrol; or stereoisomers, esters or pharmaceutically acceptable salts thereof.
  • Megestrol material is megestrol acetate.
  • Megestrol material has a wide use, and is used as anti-tumor agent to advanced breast cancer and endometrial cancer; auxiliary therapy in a treatment of breast cancer, and medicament for treating inappetence, cachexia ,or noticeable weight bss of unknown origin in cancer or AIDS patients
  • the amount of the active ingredient in the present suspension is 1 to 15 w/v%, preferably 2 to 10 w/v%, and more preferably 3 to 9 w/v%. If the amount of the active ingredient is less than 1 w/v%, the amount for one dose becomes too large. If the amount is greater than 15 w/v%, the viscosity of final dosage form is too high, whereby the administration may be inconvenient.
  • the wetting agent used in the present suspension is pobxamer, making the active ingredient exhibit homogeneous distribution in the suspension by providing hy- drophilicity to the surface of the active ingredient.
  • Pobxamer is a non-ionic surfactant comprising copolymer of ethylene oxide and propylene oxide, prevents the caking phenomenon, and makes the redispersion of the suspension easy by forming partial charge at the surface of the active ingredient and medium enough to prevent or minimize coagulation of particles.
  • the pobxamer preferably used for the present suspension includes, but is not limited to, pobxamers 124, 184, 185, 188, 237, 338 and 407, and more preferably, pobxamer 188 or pobxamer 407.
  • the present suspension may further comprise a wetting agent selected from the group consisting of polyethyleneglycol-35 castor oil, polyethyleneglycol-40 hydrogenated castor oil, caprybcaproyl macrogol gjyceride, oleoyl macrogol gjyceride, capry ⁇ c/capric gjyceride, capry ⁇ c/capric triglyceride polyethyleneglycol-4 ester and derivatives thereof, glyceryl monooleate, polyethyleneglycol-40 stearate, glyceryl citrate/lactate/ ⁇ noleate/oleate, pofyoxyethylene (20) isohexadecyl ether, propylene glycol monolaurate, propylene glycol monocaprylate, sodium lauryl sulfate, dioctylsulfosuccinate, and mixtures thereof.
  • a wetting agent selected from the group consisting of polyethyleneglycol-35 castor oil, polyethyleneglycol-40 hydrogenated
  • the present suspension may further comprise a wetting agent selected from the group consisting of polyethyleneglycol-35 castor oil, po]yethyleneglycol-40 hydrogenated castor oi, capry ⁇ c/capric gjyceride, polyethyleneglycol-40 stearate, and mixtures thereof.
  • the amount of the wetting agent in the present suspension is 0.0001 to 0.5 w/v%, preferably 0.001 to 0.4 w/v%, and more preferably 0.003 to 0.3 w/v%. If the amount of the wetting agent is less than 0.0001 w/v%, the wetting of the active ingredient is not sufficient, and so the active ingredient may float or settle down easily. If the amount is greater than 0.5 w/v%, the wetting of the active ingredient is excessive, and so the sedimentation vebcity may increase.
  • Viscosity controlling agent decreases the sedimentation vebcity of the dispersed active ingredients by maintaining the viscosity of the suspension at a constant level, and so minimizes or delays the formation of precipitates to distribute the active ingredients homogeneously in the whole suspension during the period of circulation.
  • the viscosity controlng agent guarantees an intake of a pre-determined amount of active ingredient.
  • the sedimentation vebcity decreases as the suspension's viscosity increases, but too high viscosity may make intake difficult to patients.
  • the viscosity controlng agent used in the present invention is hydrated in aqueous solution to exhibit viscosity, or floats in aqueous solution without sinking rapidly, thereby delaying the sedimentation.
  • the viscosity controlling agent used in the present suspension is not limited specially as bng as it can provide a desired viscosity to the suspension.
  • the viscosity controlling agent is selected from the group consisting of carbomer, polyethyleneoxide with a molecular weight of 5,000 to 5,000,000, hydroxypropylmethybelubse, hy- droxypropybeltubse, xanthan gum, gua gum, tragacanth gum, locust bean gum, carrageenan, polyvinylpyrrolidone, polyvinylabohol, vinylpyrrolidone-vinylacetate copolymer, microcrystalne celubse-carboxymethybeltubse sodium mixture, micronized crospovidone, carboxymethybelubse and derivatives thereof (for example, sodium carboxymethylcelluloseose and cabium carboxymethybelubse), alginic acid and derivatives thereof (for example, sodium
  • the viscosity controlling agent is selected from the group consisting of carbomer, polyethyleneoxide with a molecular weight of 5,000 to 5,000,000, hydroxypropylmethybelubse, hydroxypropybelulose, xanthan gum, microcrystalne celubse- carboxymethybelubse sodium mixture, slcone emulsion, glycerol, and mixtures thereof.
  • the viscosity controlng agent is selected from the group consisting of carbomer 934P, carbomer 97 IP, carbomer 974P, and mixtures thereof. Most preferably, the viscosity controlng agent is carbomer 97 IP.
  • the amount of the viscosity controlng agent in the present suspension is 0.01 to 10 w/v%, preferably 0.05 to 5 w/v%, more preferably 0.1 to 4 w/v%. If the amount of the viscosity controlng agent is less than 0.01 w/v%, the physical stability of the suspension (i.e. sedimentation ratio) may not be maintained property, and so the active ingredient may float or precipitate easily. If the amount is greater than 10 w/v%, the viscosity is too high, and so the production may become difficult, and the intake to patients may be difficult. [67] [68] (4) Buffers, preservatives, sweeteners, flavors and antifoaming agents
  • the present suspension may further comprise buffer, preservative, sweet ener, flavor, antifoaming agent, or mixtures thereof.
  • the buffer can be used to provide a suspension which is easy to drink, by maintaining the suspension's pH at a constant level during the period of circulation, and providing appropriate acidity to the suspension.
  • the buffer in the present invention can be selected freely from pharmaceutically acceptable conventional buffers.
  • citric acid, sodium citrate, tartaric acid and salts thereof, fumaric acid, or sodium acetate can be used as the buffer.
  • the preservative can be used to prevent the chemical deterioration of products during the period of circulation.
  • the preservative in the present invention can be selected freely from pharmaceutically acceptable conventional preservatives.
  • the preservative can be selected from benzoic acid, sodium benzoate, methyl paraoxybenzoate, ethyl paraoxybenzoate, (iso)propyl paraoxybenzoate, (iso)butyl paraoxybenzoate, sorbic acid, potassium sorbate, sodium sorbate, dehydroacetic acid, sodium dehydroacetate, chbrobutanol, benzalkonium chloride, benzenthonium chbride, phenol (p type), cresol, chbrocresol, and benzyl abohol. More preferably, sodium benzoate can be used.
  • the sweetener and flavor can be used to improve the administration compliance by providing a good taste to patients in administration to reduce aversion to the administration.
  • the sweetener in the present invention can be selected freely from pharmaceutically acceptable conventional sweeteners.
  • the sweetener can be selected from sucrose, fructose, honey, sodium saccharin, cydamate, aspartame, xy ⁇ tol, erythritol, acesutfame or the like. More preferably, sucrose can be used.
  • the flavor in the present invention can be selected freely from pharmaceutically acceptable conventional flavors.
  • lemon lime flavor, lemon essence, strawberry flavor, banana flavor, chocolate flavor, milk flavor or the like can be used, but are not limited thereto.
  • the antifoaming agent increases convenience in production and administration of the suspension by suppressing the generation of bubbles when the suspension is shaken in formulation and administration.
  • the antifoaming agent in the present invention can be selected freely from pharmaceutically acceptable conventional antifoaming agents.
  • simethicone, simethicone emulsion, methyl oleate, glyceryl oleate, sorbitan laurate, sorbitan oleate or the like can be used, but are not limited thereto.
  • buffer preservative, sweetener, flavor and antifoaming agent.
  • the amounts of the buffer, preservative, sweetener, flavor and antifoaming agent used in the present suspension are not limited specially. A skied artisan can choose a preferable amount of use for each of them, depending on a desired state of the suspension.
  • the suspension according to the present invention comprises the components as shown in the following Table 1.
  • the suspension according to the present invention comprises the components as shown in the following Table2.
  • a suspension was prepared according to the composition shown in the following Table 4. [102] [Table 4] [103] Composition of the suspension in Example 1
  • Example 9 The same procedures as the steps (3) and (4) in Example 1 were conducted. [131] [132] Examples 9 to 11 [133] Suspensions for Examples 9 to 11 were prepared respectively, according to the compositions shown in the folbwing Table 7. The concentration of megestrol acetate was increased, and in order to maintain suitable physical stability, the wetting agent and the viscosity controlng agent were adjusted property, to prepare oral suspensions of the compositions shown in the foDowing Table 7.
  • [145] - Test method The measurements were conducted according to a method described in Korean Patent No. 0211192 by Bristol-Myers Squibb Company. Concretely, about 5OmL of sample was placed in a cylinder marked with degrees in volume unit, and sealed tightly. After keeping the sample in a cylinder at room temperature for one week, the sedimentation height was measured, and the sedimentation ratio was calculated by the following equation.
  • High sedimentation ratio means that the suspension is physically stable. As can be seen from Table 8, the suspensions according to the present invention exhibited high sedimentation ratios after being kept at room temperature for one week, which shows that they were physically stable regardless of whether they were flocculated or not.
  • Test Example 2 Sedimentation velocity according to temperature
  • Viscosity is one of important physical properties of suspension. Viscosity of suspension is an important factor for maintaining the physical stability of the suspension system. Generally, as the viscosity becomes higher, the physical stability of the system, i.e., the sedimentation ratio, becomes higher. However, the increase of the viscosity for the sake of physical stability of the system results in bwering flowabi ⁇ ty of the suspension, which may cause inconvenience in administration to patients. Therefore, it is very important to maintain the viscosity of suspension to an appropriate level enough to provide the physical stability and the easiness of administration.
  • the surface of solid (liquid or gas) in contact with aqueous solution takes charge, and withdraws counter-charged ions (counter ions) in the solution, to form electrical double layer near the surface.
  • surface-activating ions for example, surfactants
  • they are adsorbed specifically onto the so ⁇ d surface, and change the surface potential greatly.
  • Zeta potential may be a factor for determining stability of colloidal particles. If the zeta potential increases, the electrically charged amount increases, and the repulsion becomes strong, thereby improving the stability of colloidal partides. If the zeta potential goes to 0, the repulsion between the partides becomes weak, thereby destabilizing the partides and causing coagulation.
  • the zeta potential is used as an index to represent the property of colloidal partides, especially physical stability thereof.
  • the present test was to compare and verify the physical stability of suspension by measuring the surface potential ( ⁇ -potential, Zeta-potential) of partides.
  • Example was dose to 0, whereas that of Example 6 was -14.3 which was relatively far from 0. This shows that the stability of the suspension of Example 6 was improved by repulsion between partides that was caused from the relative partial negative charge on the surface of megestrol acetate in Example 6, in comparison with the Megace oral suspension.
  • the present suspension has an advantage of providing easiness in re- dispersing when it is re-suspended after a long-term storage, which is consistent with the results of the sedimentation vebcity measurements of Test Examples 1 and 2.
  • the monkey size distribution in suspension is a very important factor characterizing the physical stablty (for example, sedimentation ratio, etc.) of the formulation. Generally, as the monkeye size becomes smaller, the sedimentation ratio increases, and the physical stablty is improved.
  • the physical stablty for example, sedimentation ratio, etc.
  • the megestrol acetate partides existed separately from each other by the strong repulsion due to the partial charge on the surface of megestrol acetate particles, thereby exhibiting small change in particle size before and after the ultrasonication.
  • the long-term physical stability of the present suspension comes from the strong repulsion between the partides in the suspension.
  • the present invention provides a stable oral suspension of megestrol acetate.
  • the suspension of megestrol material according to the present invention has remarkably excellent sedimentation ratio, and so provides relatively excellent dispersion state of active ingredient during the period of circulation, in spite of relatively bw viscosity compared with Megace oral suspension (Bristol-Myers Squibb Company) which is currently on sale. Therefore, patients can take the medicament easily, and the amount of megestrol material in each administration can be maintained constantly.
  • the suspension of megestrol material according to the present invention shows rapid dissolution vebcity, and so when it is administered, the rapid exhibition of effect of the active ingredient can be expected.
  • the suspension of the present invention has excellent stability depending on temperature, and so the change in quality according to the storage and circulation conditions is relatively small, thereby providing higher quality of medicaments to patients and contributing to improve the quality of life.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dispersion Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Cette invention concerne une suspension stable comprenant un matériau à base de megestrol en tant que principe actif, un poloxamère en tant qu'agent mouillant et un agent régulateur de viscosité.
PCT/KR2007/004972 2006-10-19 2007-10-11 Suspension d'un matériau à base de megestrol pharmaceutiquement stable Ceased WO2008048018A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN2007800430440A CN101553208B (zh) 2006-10-19 2007-10-11 甲地孕酮物质的药学稳定的混悬液

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2006-0102003 2006-10-19
KR1020060102003A KR20080035374A (ko) 2006-10-19 2006-10-19 약제학적으로 안정한 메게스트롤 물질의 현탁액제

Publications (1)

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WO2008048018A1 true WO2008048018A1 (fr) 2008-04-24

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KR (1) KR20080035374A (fr)
CN (1) CN101553208B (fr)
TR (1) TR200902923T2 (fr)
WO (1) WO2008048018A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017218894A1 (fr) * 2016-06-16 2017-12-21 Cutispharma, Inc. Composition et procédé de suspension d'inhibiteur de pompe à protons
US10751333B1 (en) 2019-07-16 2020-08-25 Cutispharma, Inc. Compositions and kits for omeprazole suspension
US11446246B2 (en) 2016-09-09 2022-09-20 Azurity Pharmaceuticals, Inc. Suspensions and diluents for metronidazole and baclofen
US11633478B2 (en) 2019-07-16 2023-04-25 Azurity Pharmaceuticals, Inc. Compositions and kits for Omeprazole suspension
US11903946B2 (en) 2012-12-07 2024-02-20 Ceva Sante Animale Triazine formulations with a second active ingredient and surfactant(s)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105769763A (zh) * 2016-05-25 2016-07-20 西安德天药业股份有限公司 一种醋酸甲地孕酮纳米混悬液及其制备方法和应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5338732A (en) * 1991-06-18 1994-08-16 Bristol-Myers Squibb Company Megestrol acetate formulation
US20020028794A1 (en) * 2000-07-21 2002-03-07 Brubaker Greg Allen Megestrol acetate suspension
US6593320B2 (en) * 1998-04-20 2003-07-15 Pharmaceutical Resources Inc. Flocculated suspension of megestrol acetate
US20050233001A1 (en) * 2002-04-12 2005-10-20 Elan Pharma International Ltd. Nanoparticulate megestrol formulations

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5338732A (en) * 1991-06-18 1994-08-16 Bristol-Myers Squibb Company Megestrol acetate formulation
US6593320B2 (en) * 1998-04-20 2003-07-15 Pharmaceutical Resources Inc. Flocculated suspension of megestrol acetate
US20020028794A1 (en) * 2000-07-21 2002-03-07 Brubaker Greg Allen Megestrol acetate suspension
US20050233001A1 (en) * 2002-04-12 2005-10-20 Elan Pharma International Ltd. Nanoparticulate megestrol formulations

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11911391B2 (en) 2012-12-07 2024-02-27 Ceva Sante Animale Triazine formulations with a second active ingredient and surfactant(s)
US11903947B2 (en) 2012-12-07 2024-02-20 Ceva Sante Animale Triazine formulations with a second active ingredient and surfactant(s)
US11903946B2 (en) 2012-12-07 2024-02-20 Ceva Sante Animale Triazine formulations with a second active ingredient and surfactant(s)
US11813253B2 (en) 2016-06-16 2023-11-14 Azurity Pharmaceuticals, Inc. Composition and method for proton pump inhibitor suspension
US11207307B2 (en) 2016-06-16 2021-12-28 Azurity Pharmaceuticals, Inc. Composition and method for proton pump inhibitor suspension
WO2017218894A1 (fr) * 2016-06-16 2017-12-21 Cutispharma, Inc. Composition et procédé de suspension d'inhibiteur de pompe à protons
US11446246B2 (en) 2016-09-09 2022-09-20 Azurity Pharmaceuticals, Inc. Suspensions and diluents for metronidazole and baclofen
US12458593B2 (en) 2016-09-09 2025-11-04 Azurity Pharmaceuticals, Inc. Suspensions and diluents for metronidazole and baclofen
US11771686B2 (en) 2019-07-16 2023-10-03 Azurity Pharmaceuticals, Inc. Compositions and kits for omeprazole suspension
US11633478B2 (en) 2019-07-16 2023-04-25 Azurity Pharmaceuticals, Inc. Compositions and kits for Omeprazole suspension
US11103492B2 (en) 2019-07-16 2021-08-31 Azurity Pharmaceuticals, Inc. Compositions and kits for omeprazole suspension
US11911473B2 (en) 2019-07-16 2024-02-27 Azurity Pharmaceuticals, Inc. Compositions and kits for omeprazole suspension
US10751333B1 (en) 2019-07-16 2020-08-25 Cutispharma, Inc. Compositions and kits for omeprazole suspension
US12042539B2 (en) 2019-07-16 2024-07-23 Azurity Pharmaceuticals, Inc. Compositions and kits for Omeprazole suspension
US12329752B2 (en) 2019-07-16 2025-06-17 Azurity Pharmaceuticals, Inc. Compositions and kits for omeprazole suspension
US12440566B2 (en) 2019-07-16 2025-10-14 Azurity Pharmaceuticals, Inc. Compositions and kits for omeprazole suspension

Also Published As

Publication number Publication date
TR200902923T2 (tr) 2009-06-22
CN101553208A (zh) 2009-10-07
CN101553208B (zh) 2012-01-25
KR20080035374A (ko) 2008-04-23

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