Medical propellant composition

Abstract

The main problem addressed by the present disclosure is to provide a novel low-GWP medical propellant.　As a means for solving this problem, a medical propellant composition containing a propellant is provided, said propellant containing a C2 olefin compound.

Description

Medical aerosol composition

[0001] The present disclosure relates to a medical aerosol composition.

[0002] Currently, R134a, R227ea, R152a, etc. are used as medical aerosols (Patent Documents 1 and 2). However, these have a high global warming potential (GWP).

[0003] Japanese Patent Publication No. 2004-525148 Japanese Patent Publication No. 2014-513146

[0004] An object of the present disclosure is to provide a medical composition containing a medical aerosol using a new low-GWP composition.

[0005] Item 1. A medical aerosol composition containing an aerosol, wherein the aerosol contains an olefinic compound having 2 carbon atoms (C2 olefin compound). Item 2. The medical aerosol composition according to Item 1, wherein the aerosol has a boiling point of -28°C to -15°C, a vapor pressure at 20°C of 0.35 Mpa to 0.6 Mpa, and a GWP of 5 or less. Item 3. The medical aerosol composition according to Item 1 or 2, wherein the C2 olefin compound contains cis-1,2-difluoroethylene (HFO-1132(Z)). Item 4. The medical aerosol composition according to any one of Items 1 to 3, wherein the aerosol contains HFO-1132(Z) and an additional compound capable of forming an azeotropic or azeotrope-like composition with HFO-1132(Z). Item 5. Further containing an active ingredient, wherein the active ingredient is at least one selected from the group consisting of fluticasone, mometasone, beclomethasone, ciclesonide, budesonide, salbutamol, glycopyrrolate, formoterol, arformoterol, bambuterol, clenbuterol, salmeterol, indacaterol, olodaterol, vilanterol, and tiotropium, and pharmaceutically acceptable salts and derivatives thereof. Item 6. The medical aerosol composition according to any one of Items 1 to 5, wherein the aerosol is contained in an amount of 70% by mass or more based on the total amount of the medical aerosol composition.

[0006] A new low-GWP medical aerosol is provided.

[0007] <Definition of Terms> In this specification, the term "propellant" refers to a liquefied gas that is filled into a pressure-resistant container along with the active ingredient, etc., when manufacturing a medical propellant composition, and which can generally be liquefied by pressurizing at or near room temperature.

[0008] In this specification, the term “medical propellant composition containing a propellant” includes at least (1) the propellant itself (including a mixture of multiple types of propellants) and (2) a composition that further contains at least an active ingredient and can be used as a pharmaceutical product.

[0009] In this specification, the term "azeotropic composition" means a composition that can be treated substantially in the same manner as an azeotropic composition. Specifically, in this specification, the term "azeotropic composition" means a mixture of two or more substances at their constant boiling points that behave substantially as a single substance. One characteristic of an azeotropic composition is that the composition of the vapor produced by evaporation or distillation of the liquid does not substantially change from the composition of the liquid. That is, in this specification, a mixture is called an azeotropic composition when it boils, distills or refluxes without a substantial change in composition. Specifically, in this disclosure, a composition is defined as an azeotropic composition if the difference between the bubble point vapor pressure of the composition and the dew point vapor pressure of the composition at a certain temperature is 3% or less (relative to the bubble point pressure).

[0010] 1. Medical propellant composition 1.1 Propellant The propellant of this disclosure comprises at least one C2 olefin compound. Examples of C2 olefin compounds include cis-1,2-difluoroethylene (HFO-1132(Z)), trans-1,2-difluoroethylene (HFO-1132(E)), 1,1-difluoroethylene (HFO-1132a), 1,1,2-trifluoroethylene (HFO-1123), 1,-chloro-1,2,2-trifluoroethylene (CTFE), 1-chloro-1-fluoroethylene (HCFO-1131a), trans-1-chloro-2-fluoroethylene (HCFO-1131(E)), cis-1-chloro-2-fluoroethylene (HCFO-1131(Z)), 1-chloro-2,2-difluoroethylene (HCFO-1122), 1-chloro-1,2-difluoroethylene (HCFO-1122a), fluoroethylene (HFO-1141), and ethylene.

[0011] The above-mentioned C2 olefin compounds have a lower global warming potential (GWP) compared to conventionally used medical propellants (such as R134a, R227ea, and R152a).

[0012] C2 olefin compounds can be used as propellants, either individually or in mixtures. Preferred C2 olefin compounds have boiling points and vapor pressures at 20°C that are similar to those of conventionally used medical propellants, i.e., boiling points of -60°C to 0°C, preferably -40°C to -10°C, more preferably -28°C to -15°C, and vapor pressures at 20°C of 0 MPa to 1.8 MPa, preferably 0.2 MPa to 0.8 MPa, more preferably 0.35 MPa to 0.6 MPa. When used individually, HFO-1132(Z) is preferred as a C2 olefin compound that satisfies the above conditions and also has a GWP of 5 or less.

[0013] 1.2 Additional Compounds In addition to C2 olefin compounds, the propellants of this disclosure may further contain fluorocarbon compounds other than C2 olefin compounds, fluorine-free organic compounds, or carbon dioxide (R744) as additional compounds. The additional compounds may consist of one compound alone or two or more compounds.

[0014] Additional compounds include "fluorocarbon compounds," such as hydrofluoroolefins (HFOs), hydrochlorofluoroolefins (HCFOs), chlorofluorocarbons (CFCs), hydrochlorofluorocarbons (HCFCs), and hydrofluorocarbons (HFCs). Specifically, these include R32, HFC-143a, HFC-134a, HFO-1243zf, HFC-245cb, HCFC-1122, HCFC-124, CFC-1113, and 3,3,3-trifluoropropyne. These may be used individually or in combination.

[0015] Additional compounds that do not contain fluorine include propane (R290), propylene (R1270), butane (R600), isobutane (R600a), acetylene, and methylamine. These may be used individually or in combination.

[0016] If the propellant contains additional compounds, it is preferable that the boiling point is between -28°C and -15°C, the vapor pressure at 20°C is between 0.35 MPa and 0.6 MPa, and the GWP is 5 or less.

[0017] 1.3 Azeotrope or Azeotropic Propellant When the medical propellant compositions of this disclosure are used in combination with an active ingredient, it is preferable that a nearly constant amount of the active ingredient can be sprayed regardless of the number of sprays. For this reason, if the propellant of this disclosure is a mixture, it is preferable that it be azeotropic or azeotropic. When the propellant is azeotropic or an azeotropic mixture, the component ratio of the propellant in the residual liquid does not change nearly regardless of the number of sprays, so that a nearly constant amount of the active ingredient can be sprayed. The combination of C2 olefin compounds and additional compounds that forms an azeotrope or azeotropic mixture is not particularly limited, but it is preferable that the boiling point and vapor pressure at 20°C be close to those of conventionally used medical propellants. That is, it is preferable that the boiling point is -28°C or higher and -15°C or lower, and the vapor pressure at 20°C is 0.35 MPa or higher and 0.6 MPa or lower. Combinations that satisfy the above conditions and also result in a GWP of 5 or less include, for example, propellants with a weight ratio of HFO-1132(Z):R1234zeE = 48:52 to 54:46, and propellants with a weight ratio of HFO-1132(Z):R600a = 75:25 to 81:19.

[0018] The propellant of this disclosure may contain other components in addition to the C2 olefin compounds and additional compounds, to the extent that they do not impair the above-mentioned properties and effects. In this regard, it is preferable that the propellant of this disclosure contains 99.5% by mass or more of the total C2 olefin compounds and additional compounds relative to the entire propellant, more preferably 99.75% by mass or more, and even more preferably 99.9% by mass or more.

[0019] 1.4 Active Ingredients The medical propellant compositions of this disclosure may contain effective amounts of conventionally known active ingredients. Examples of such active ingredients include fluticasone, mometasone, beclomethasone, ciclesonide, budesonide, salbutamol, glycopyrronium, formoterol, alformoterol, bambuterol, clenbuterol, fenoterol, salmeterol, indacaterol, orodaterol, vilanterol, and tiotropium, as well as pharmaceutically acceptable salts and derivatives thereof. These active ingredients may be used individually or in combination.

[0020] The active ingredient is mixed with a propellant, solvent, etc., and included in the medical propellant composition as a solution or suspension. When the active ingredient is included in the medical composition as a suspension, the active ingredient may be finely divided by conventionally known methods.

[0021] 1.5 Additives The medical propellant composition of this disclosure may contain additives commonly used in pharmaceuticals, in addition to the propellant and active ingredients, such as buffering agents, viscosity modifiers, surfactants, isotonic agents, stabilizers, preservatives, antioxidants, pH adjusters, etc. Furthermore, the medical propellant composition of this disclosure may contain colorants, fragrances, flavoring agents, sweeteners, etc., as needed. These may be used individually or in combination of two or more as appropriate, and appropriate amounts may be blended. From the viewpoint of quality stability of the medical composition, it is preferable that the propellant constitutes 50% by mass or more of the total medical propellant composition containing the above components, and particularly preferable that it constitutes 70% by mass or more.

[0022] The present disclosure will be further described below with reference to examples, but the present disclosure is not limited in any way to these examples.

[0023] Example 1 Table 1 shows the GWP, boiling point, and vapor pressure at 20°C for each medical propellant composition. The GWP was evaluated based on the values ​​(100-year values) from the IPCC (Intergovernmental Panel on Climate Change) 45th Assessment Report (AR4). The GWP of HFO-1132(E), which is not listed in AR4, was set to 1 or less based on the description <<1 in WMO (World Meteorological Organization) GAW Report No. 278 (2022). The GWP of HFO-1132(Z) was set to 1 or less, based on the GWP of HFO-1132(E). The GWP of HFO-1123 was set to 1 or less, based on the value of 0.3 described in WO2015 / 141678.

[0024] Table 1 below shows that all compositions containing C2 olefin compounds as propellants have low GWP (Gross Wave Pressure). Furthermore, HFO-1132(Z) has a boiling point and vapor pressure at 20°C similar to conventionally used medical propellants, indicating its usefulness as a substitute for conventional medical propellants.

[0025]

[0026] Table 2 shows the GWP, boiling point, and vapor pressure at 20°C for an azeotrope-like composition containing HFO-1132(Z) and additional compounds in Example 2. The evaluation method was the same as in Example 1.

[0027] All of the compositions have low GWP (Global Warming Potential) and possess boiling points and vapor pressures at 20°C similar to conventionally used medical propellants, indicating their usefulness as substitutes for conventional medical propellants.

[0028]

[0029] Example 3: Table 3 shows the solubility of salbutamol, one of the active ingredients, in a composition containing the propellant of this disclosure. Solubility was calculated using the thermodynamic property estimation software "COSMOtherm" from Molsys Co., Ltd.

[0030] Table 3 below shows that a conventionally known effective amount of salbutamol dissolves in the composition of this disclosure. Therefore, the composition of this disclosure is useful as a substitute for conventional medical propellants.

[0031]

Claims

1. A medical propellant composition comprising a propellant, wherein the propellant comprises a carbon-2 olefin compound (C2 olefin compound).

2. The medical propellant composition according to claim 1, wherein the propellant has a boiling point of -28°C to -15°C, a vapor pressure of 0.35 MPa to 0.6 MPa at 20°C, and a GWP of 5 or less.

3. The medical propellant composition according to claim 1, wherein the C2 olefin compound comprises cis-1,2-difluoroethylene (HFO-1132(Z)).

4. The medical propellant composition according to any one of claims 1 to 3, wherein the propellant comprises HFO-1132(Z) and an additional compound capable of forming an azeotrope or azeotrope-like composition with HFO-1132(Z).

5. The composition according to claim 4, further comprising an active ingredient, wherein the active ingredient comprises at least one selected from the group consisting of fluticasone, mometasone, beclomethasone, ciclesonide, budesonide, salbutamol, glycopyrrolate, formoterol, alformoterol, bambuterol, clenbuterol, salmeterol, indacaterol, orodaterol, vilanterol, and tiotropium, and pharmaceutically acceptable salts and derivatives thereof.

6. The medical propellant composition according to claim 4, wherein the propellant is contained in an amount of 70% by mass or more of the total medical propellant composition.

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