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WO2021033898A1 - Composition aqueuse contenant du désoxycholate de sodium, stable contre la précipitation - Google Patents

Composition aqueuse contenant du désoxycholate de sodium, stable contre la précipitation Download PDF

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Publication number
WO2021033898A1
WO2021033898A1 PCT/KR2020/007761 KR2020007761W WO2021033898A1 WO 2021033898 A1 WO2021033898 A1 WO 2021033898A1 KR 2020007761 W KR2020007761 W KR 2020007761W WO 2021033898 A1 WO2021033898 A1 WO 2021033898A1
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aqueous solution
phosphate
nadc
aqueous
sodium deoxycholate
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Korean (ko)
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아영창
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Biobelief Co Ltd
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Biobelief Co Ltd
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    • 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
    • A61K9/08—Solutions
    • 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
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • 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
    • A61K47/02—Inorganic compounds
    • 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
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/24—Phosphorous; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/345—Alcohols containing more than one hydroxy group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/63—Steroids; Derivatives thereof
    • 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
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/06—Preparations for care of the skin for countering cellulitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/52—Stabilizers

Definitions

  • the present invention relates to an aqueous composition comprising sodium deoxycholate, which has a pH similar to the physiological pH (7.35 to 7.45) observed in the plasma of a healthy person, and is stable from precipitation even with a low concentration of sodium deoxycholate. will be.
  • Sodium deoxycholate (C 24 H 39 NaO 4 , molecular weight: 414.55 g/mol, CAS No: 302-95-4, NaDC) is deoxycholic acid (C 24 H 40 O 4 , molecular weight: It is a sodium salt of 415.55 393.6 g/mol, CAS No: 83-44-3, DCA), and its specific molecular structure is the same as the following Formula 1, and is known to exhibit a solubility of 33.3% by weight or more in water at 15 degrees Celsius.
  • it is an anionic surfactant with a critical micelle concentration (CMC) of 2 to 6 mM measured in water.
  • CMC critical micelle concentration
  • NaDC acts as an anionic surfactant and promotes the conversion of a substance having low solubility in water into a solution mixture containing water as the main solvent.
  • NaDC is reported to have a property of removing fat when injected into a tissue containing fat and fat accumulated in vivo. More specifically, International Patent Application Nos. WO 2005/117900 and WO 2005/112942, US Patent Application No. US2005/0261258; US2005/0267080; US2006/127468; And in US2006/0154906 and the like, it is known that NaDC is a material having an excellent effect of removing or reducing fat cells in the body, and is helpful in improving obesity. Therefore, such an aqueous solution containing NaDC as a main component is very usefully used not only for injections for subcutaneous injection prepared for the purpose of adipocyte degradation, but also for the manufacture of cosmetics for the purpose of adipocyte degradation. In addition, NaDC is very useful as a surfactant for studying the structure of membrane proteins for biological cell experiments or for the development of new drugs for the purpose of extracting intracellular substances by disrupting the cell wall.
  • Korean Patent Registration Nos. 10-1751585, 10-1919269, etc. in aqueous pharmaceutical compositions for the purpose of preventing the occurrence of precipitation in aqueous pharmaceutical compositions containing NaDC at a concentration lower than 2% by weight as a main component.
  • a technique for adjusting the pH of the composition from about 8.1 to about 8.5 was proposed.
  • this technology is to secure the stability of an aqueous pharmaceutical composition containing NaDC in a pH range different from 7.35 to 7.45, which is the physiological pH observed in plasma of healthy humans, so it is a technology as an injection formulation directly injected into the subcutaneous tissue. It cannot be said that the degree of completion is high.
  • the above techniques include preparing a basic aqueous solution first, preparing a first solution composition having a pH of 10 or higher by adding NaDC to the basic aqueous solution, and adding HCl to the first solution composition to obtain a target pH It is described that the preparation is complete including the step of adjusting to, and at this time, if the rate of titration by adding the HCl is too fast, solid content may be precipitated. That is, the above technology has a problem that the manufacturing process is very difficult and difficult.
  • the present invention was created to overcome the problems of the prior art described above, and has a pH range close to 7.35 to 7.45, which is a physiological pH observed in plasma of a healthy person, and is stable with an easier manufacturing method compared to the existing technology. It is intended to provide an aqueous composition containing sodium deoxycholate that can be prepared as, and there is no precipitation, and is stable from precipitation.
  • An embodiment of the present invention is 0.5 to 2% by weight of sodium deoxycholate; And 0.5 to 10 mmmol / kg of a phosphate (phosphate, PO 4 ) aqueous solution for pH adjustment containing a phosphate aqueous solution containing; including, by adjusting the pH to have a range of 7.0 to 8.0, sodium deoxycholate stable from precipitation It provides an aqueous composition comprising a.
  • phosphate phosphate, PO 4
  • the aqueous composition comprising the sodium deoxycholate comprises the steps of preparing an aqueous solution for adjusting the pH; And adding 0.5 to 2% by weight of sodium deoxycholate to the prepared aqueous solution for pH adjustment, and adjusting the pH to have a range of 7.0 to 8.0.
  • the aqueous solution for pH adjustment may have a pH in the range of 5.0 to 7.4.
  • the pH adjusting solution may be a mixed aqueous solution of a basic phosphate solution containing a phosphate (PO 4) an acidic phosphate solution and a phosphate (PO 4) comprising a.
  • aqueous solution for pH adjustment may further include an additive for controlling osmotic pressure, which is non-dissolving and water-soluble, including mannitol.
  • the aqueous composition containing sodium deoxycholate stable from precipitation contains sodium deoxycholate (NaDC), which is a salt of deoxycholic acid (DCA), at a low concentration of 0.5 to 2% by weight, , Even in the pH range of 7.0 to 8.0, which is similar to the physiological pH (7.35 to 7.45) observed in the plasma of a healthy person, phenomena such as solids precipitation, suspension, and gelation do not occur, there is a very stable effect from precipitation.
  • NaDC sodium deoxycholate
  • DCA deoxycholic acid
  • the aqueous composition containing sodium deoxycholate stable from precipitation is not only a pharmaceutical composition for subcutaneous injection prepared for the purpose of adipocyte degradation, but also for the manufacture of cosmetics for the purpose of adipocyte degradation.
  • a surfactant for biological cell experiments or membrane protein structure studies for new drug development is not only a pharmaceutical composition for subcutaneous injection prepared for the purpose of adipocyte degradation, but also for the manufacture of cosmetics for the purpose of adipocyte degradation.
  • FIG. 2 shows an image after refrigerating the aqueous composition containing NaDC prepared in Comparative Examples 2-1 to 2-4 for 1 week and then storing at room temperature for 1 day.
  • FIG. 3 shows an image of an aqueous composition containing NaDC prepared in Comparative Examples 3-1 to 3-6 after being refrigerated for 1 week and then stored at room temperature for 1 day.
  • FIG. 4 shows an image after the aqueous composition containing NaDC prepared in Comparative Examples 4-1 to 4-16 was refrigerated for 1 week and then stored at room temperature for 1 day.
  • FIG. 5 shows images after refrigerating the aqueous composition containing NaDC prepared in Examples 2-1 to 2-12 for 1 week, and then storing at room temperature for 1 day.
  • stable from sedimentation means that not only solid content precipitation, but also suspension and gelation do not occur, so that it is stable from precipitation to a degree suitable for use as an injection for subcutaneous injection.
  • An embodiment of the present invention is 0.5 to 2% by weight of sodium deoxycholate; And 0.5 to 10 mmmol / kg of a phosphate (phosphate, PO 4 ) aqueous solution for pH adjustment containing a phosphate aqueous solution containing; including, by adjusting the pH to have a range of 7.0 to 8.0, sodium deoxycholate stable from precipitation It provides an aqueous composition comprising a.
  • phosphate phosphate, PO 4
  • the aqueous composition containing sodium deoxycholate is first, the step of preparing an aqueous solution for pH adjustment; And adding 0.5 to 2% by weight of sodium deoxycholate to the prepared aqueous solution for pH adjustment, and adjusting the pH to have a range of 7.0 to 8.0.
  • the aqueous solution composition comprising sodium deoxycholate according to an embodiment of the present invention is preferably according to the above preparation sequence and method in order to significantly improve a stable effect from precipitation.
  • the aqueous solution for pH adjustment is preferably prepared to have a pH in the range of 5.0 to 7.4. That is, the aqueous composition containing sodium deoxycholate stable from precipitation according to an embodiment of the present invention is prepared so that the pH of the aqueous solution for pH adjustment has a pH in the range of 5.0 to 7.4, and then 0.5 to 2% by weight of sodium dioxycholate is By adding, by increasing the pH compared to the pH of the aqueous solution for pH adjustment, the pH can be adjusted to have a range of 7.0 to 8.0.
  • sodium deoxycholate is mixed with a basic aqueous solution to prepare a first solution composition having a pH of 10 or more, and then HCl is added to the first solution composition to lower the pH. It is a completely different method from the method controlled by, and is a method capable of preparing an aqueous composition containing sodium deoxycholate that is more stable from precipitation than this method.
  • the aqueous solution for pH adjustment may be prepared to have a pH in the above range by using an acidic aqueous solution for pH adjustment alone, or a mixture of the acidic aqueous solution for pH adjustment and a basic aqueous solution for pH adjustment.
  • aqueous solution for pH adjustment when an acidic aqueous solution for pH adjustment is used alone, an aqueous solution prepared from phosphoric acid or an acidic phosphate containing PO 4 may be used alone.
  • an aqueous solution prepared from an acidic phosphate containing phosphoric acid or PO 4 , and a basic phosphate aqueous solution containing PO 4 Using a mixture; It may be the case of using a mixture of an aqueous acidic phosphate solution containing PO 4 and an aqueous basic phosphate solution not containing PO 4.
  • a mixed aqueous solution of a basic aqueous solution containing a phosphate and an acidic phosphate PO 4 aqueous solution containing a PO 4 it is possible to obtain an aqueous composition containing the more stable sodium deoxy cholate precipitation.
  • a basic aqueous solution not containing PO 4 may be further added and titrated.
  • the basic aqueous solution that does not contain PO 4 is generally used in the art, and its kind is not particularly limited, but an aqueous solution of sodium hydroxide (NaOH) or potassium hydroxide (KOH) is preferably used.
  • the present invention has an important technical feature in using a phosphate aqueous solution containing PO 4 at a concentration of 0.5 to 10 mmmol/kg as an aqueous solution for pH adjustment, and an aqueous composition containing sodium deoxycholate finally prepared
  • a phosphate aqueous solution containing the PO 4 can improve the excellent effect of the present invention it is very easily by the use in that it comprises a PO 4 of from 0.5 to 10 mmmol / kg concentration. More preferably, it is good to include PO 4 at a concentration of 1 to 5 mmmol/kg.
  • the concentration of PO 4 is too low, the pH is too high to have a pH of 8.0 or higher, which may cause a problem that deviates from the goal to be achieved in the present invention.
  • the difference with the pH (7.35 to 7.45) observed in the plasma of a healthy person increases, a problem in which the patient feels pain during and after the injection may occur.
  • the concentration of PO 4 is too high, phenomena such as solid content precipitation, suspension, and gelation may occur, resulting in unstable problems from precipitation.
  • the phosphate aqueous solution containing PO 4 is used as a "aqueous solution for pH adjustment", and preferably at least one aqueous solution selected from the group consisting of phosphoric acid, alkali metal-hydroxides, alkali metal-phosphates, hydrates thereof, and mixtures thereof. Can be used.
  • phosphoric acid sodium hydroxide (NaOH), potassium hydroxide (KOH), sodium dihydrogen phosphate (NaH 2 PO 4 ), sodium monohydrogen phosphate (Na 2 HPO 4 ), potassium dihydrogen phosphate (KH 2 PO 4 ) , Potassium monohydrogen phosphate (K 2 HPO 4 ), hydrates thereof and mixtures thereof may be one or more aqueous solutions selected from the group consisting of.
  • an aqueous solution of sodium dihydrogen phosphate monohydrate (NaH 2 PO 4 ⁇ H 2 O, molar weight 137.99 g/mol) may be used as an acidic phosphate aqueous solution containing PO 4 and sodium monohydrogen phosphate
  • An aqueous solution of 12 hydrate (Na 2 HPO 4 ⁇ 12H 2 O, molar weight 358.14 g/mol) can be used as a basic phosphate aqueous solution containing PO 4.
  • the aqueous solution for pH adjustment may further include an additive for controlling osmotic pressure, which is non-dissolving and water-soluble, including mannitol.
  • the osmotic pressure control additive may be included so that the osmotic pressure of the aqueous composition containing sodium deoxycholate stable from precipitation according to an embodiment of the present invention is 250 to 350 mOmol/kg. Accordingly, the osmotic pressure (280 to 290 mOsmol/kg) observed in the plasma of a healthy adult is close to the range, and when applied to a pharmaceutical injection and injected, the pain of the person receiving the injection can be further reduced.
  • the pH may be adjusted to have a range of 7.0 to 8.0.
  • the aqueous solution composition containing sodium deoxycholate stable from the precipitation has an effect that can be stably and easily prepared even in the manufacturing process.
  • the aqueous composition containing sodium deoxycholate stable from precipitation is adjusted to have a pH in the range of 7.4 to 8.0, and the physiological pH (7.35 to 7.45) and osmotic pressure (280 to 7.45) observed in the plasma of a healthy person 290 mOsmol/kg) has a similar pH and osmotic pressure, so when applied to a pharmaceutical injection and injected, there is an effect that the pain of the person receiving the injection can be reduced.
  • Water used in the "aqueous solution” of the present invention may be “sterile water” or “water for injection”. It refers to a sterile, non-pyrogenic preparation of water for injection that does not contain any bacteriostat, antimicrobial agents, or added buffers.
  • the aqueous composition containing sodium deoxycholate stable from precipitation contains sodium deoxycholate, a salt of deoxycholic acid (DCA), in a low concentration of 0.5 to 2% by weight, and a healthy person Even in the pH range of 7.0 to 8.0, which is similar to the physiological pH (7.35 to 7.45) observed in plasma, solids precipitation, suspension, and gelation do not occur, so there is a very stable effect from precipitation.
  • DCA deoxycholic acid
  • the aqueous composition containing sodium deoxycholate stable from precipitation is not only a pharmaceutical composition for subcutaneous injection prepared for the purpose of adipocyte degradation, but also a cosmetic product for the purpose of adipocyte degradation.
  • a cosmetic product for the purpose of adipocyte degradation.
  • the pH of the prepared sodium monohydrogen phosphate 12 hydrate (Na 2 HPO 4 ⁇ 12H 2 O) aqueous solution was confirmed to exhibit basicity from 8.68 to 9.26.
  • sodium dihydrogen phosphate monohydrate NaH 2 PO 4 .H 2 O
  • sodium monohydrogen phosphate ⁇ 12 hydrate Na 2 HPO 4 ⁇ 12H 2 O
  • 35.8 g was diluted with water to obtain 500 g
  • sodium dihydrogen phosphate monohydrate NaH 2 PO 4 ⁇ H 2 O, molar weight 137.99 g/mol
  • an aqueous solution of sodium monohydrogen phosphate/12 hydrate Na 2 HPO 4 ⁇ 12H 2 O, molar weight 358.14 g/mol
  • the mixed aqueous solution was diluted with water to prepare a mixed aqueous solution having PO 4 concentrations of 100, 50, 20, 10, 5, and 2 mmol/kg, respectively.
  • the pH of the prepared mixed aqueous solution was confirmed to represent a range of pH 7.02 to 7.32, as shown in Tables 4 to 5 below.
  • a mixed aqueous solution of a basic phosphate aqueous solution comprising an acidic phosphate solution and PO 4 containing PO 4, dihydrogenphosphate, sodium and monohydrate (NaH 2 PO 4 and H 2 O, mol
  • An aqueous solution having a weight of 137.99 g/mol) and an aqueous solution of sodium monohydrogen phosphate ⁇ 12 hydrate (Na 2 HPO 4 ⁇ 12H 2 O, molar weight 358.14 g/mol) were prepared, respectively, and the aqueous solutions were mixed.
  • the mixed aqueous solution was prepared so that the concentration of PO 4 was 1 mmol/kg and the pH was 7.0 to 7.1.
  • Sodium deoxycholate (NaDC) was added to each of the aqueous solutions for pH adjustment prepared in Preparation Example as shown in Tables 1 to 5 below to prepare an aqueous composition containing NaDC.
  • NaDC sodium chloride
  • KCl potassium chloride
  • mannitol aqueous composition
  • NaCl was 0.6% by weight
  • KCl was 0.76% by weight
  • mannitol was 3.75% by weight based on the content in the aqueous solution containing the final NaDC.
  • the stability against precipitation was evaluated.
  • the aqueous composition containing NaDC prepared above was separated into room temperature (about 25° C.) and low temperature (about 1° C.), respectively, and stored for 1 week.
  • room temperature about 25° C.
  • low temperature about 1° C.
  • room temperature about 25° C.
  • the stability against precipitation was evaluated, and the results are shown in Tables 1 to 7 below. As shown in Figures 1 to 6.
  • the concentration of phosphate in the acidic phosphate aqueous solution containing phosphate is 0.5 to 10 mmmol/kg; It was confirmed that the stability against precipitation was very excellent only when all the conditions in which the pH of the aqueous composition containing NaDC was in the range of 7.0 to 8.0 were satisfied (Examples 1-1 to 1-10). However, when the pH of the acidic phosphate aqueous solution containing phosphate was lower than 5.0 (Example 1-1), a weak gelation phenomenon was observed under refrigerated storage conditions at 1° C., but after 1 week refrigerated storage, then at 25° C. for 1 day. After storage at room temperature, it was converted into a clear solution again.
  • PO 4 are the phosphate concentration in the mixed aqueous solution of a basic aqueous solution containing a phosphate and an acidic phosphate PO 4 aqueous solution containing 0.5 to 10 mmmol / kg, and; It was confirmed that the stability against precipitation was very excellent only when the pH of the prepared aqueous composition containing NaDC satisfies all conditions in the range of 7.0 to 8.0 (Examples 2-1 to 2-12).
  • the content stability of NaDC was evaluated.
  • the aqueous composition containing NaDC was put in a 5 ml injection tube shown in FIG. 7 and stored for 2 weeks at room temperature, refrigerated and frozen conditions, respectively, and stability against precipitation was evaluated at 1-week intervals;
  • the content of NaDC was measured using high performance liquid chromatography (HPLC), the rate of change was calculated, and the results are shown in Table 8 below.
  • HPLC high performance liquid chromatography
  • -Calibration curve Prepared as a solution prepared by diluting NaDC in a mobile phase and prepared at 50, 100, 250, 500, 1000 ⁇ g/ml
  • Example preparation After passing the aqueous composition containing NaDC through a membrane having a pore of 0.2 ⁇ m, dilute 50 times by adding the prepared mobile phase
  • the aqueous composition containing NaDC according to Examples 2-6 and 2-10 under both freezing, refrigerating and room temperature storage conditions has stability against precipitation and stability of NaDC content. It could be confirmed that it was excellent.
  • NaDC aqueous solution prepared by making 1% by weight of NaDC in purified water just before measurement
  • the aqueous composition containing NaDC according to Examples 2-6 and 2-10 under all conditions of freezing, refrigeration and room temperature storage has a visible light transmittance of 99% or more. It could be confirmed that it was high. That is, it was confirmed that the aqueous composition containing NaDC according to Examples 2-6 and 2-10 had very excellent stability against precipitation.
  • the concentration of phosphate is 0.5 to 10 mmmol/kg
  • the pH of the aqueous solution for adjusting the pH before adding NaDC is in the range of 5.0 to 7.4
  • stability against precipitation is excellent even if 0.5 to 2% by weight of NaDC is added. I could confirm.
  • a non-electrolyte that is, a material that does not generate ions, as a water-soluble material added to control the osmotic pressure.

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Abstract

La présente invention concerne une composition aqueuse contenant du désoxycholate de sodium comprenant une solution aqueuse de phosphate comprenant une solution aqueuse d'ajustement du pH qui contient 0,5 à 2 % en poids de désoxycholate de sodium ; et une concentration de 0,5 à 10 mmol/kg de phosphate (PO4), la composition étant ajustée pour avoir un pH de 7,0 à 8,0, similaire au pH physiologique (7,35 à 7,45) observé dans le plasma de personnes saines, et est stable vis-à-vis de la précipitation même si elle contient une faible concentration de désoxycholate de sodium.
PCT/KR2020/007761 2019-08-20 2020-06-16 Composition aqueuse contenant du désoxycholate de sodium, stable contre la précipitation Ceased WO2021033898A1 (fr)

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Cited By (2)

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Publication number Priority date Publication date Assignee Title
WO2023281367A1 (fr) * 2021-07-03 2023-01-12 Lupin Limited Formulations liquides stables d'aflibercept
WO2024169912A1 (fr) * 2023-02-16 2024-08-22 南京迈诺威医药科技有限公司 Composition pharmaceutique contenant de l'acide désoxycholique et de la lidocaïne, et son utilisation

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KR102111346B1 (ko) * 2019-08-20 2020-05-22 아영창 침전으로부터 안정한 소듐디옥시콜레이트를 포함하는 수용액상 조성물

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KR20170003992A (ko) * 2014-06-27 2017-01-10 (주)메디톡스 지방 감소를 위한 담즙산 및 염의 방법 및 조성물
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