Medical propellant composition

Abstract

We offer a new low-GWP medical propellant. [Solution] A medical propellant composition comprising a propellant, wherein the propellant comprises an olefin compound having 2 carbon atoms.

Description

Technical Field

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

Background Art

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

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0004] An object of the present disclosure is to provide a medical composition including a medical injectant using a new composition with a low GWP.

Means for Solving the Problems

[0005] Item 1. A medical injectant composition including an injectant, wherein the injectant includes an olefinic compound having 2 carbon atoms (C2 olefin compounds). Item 2. The injectant is having a boiling point of -28°C to -15°C, having a vapor pressure at 20°C of 0.35 Mpa to 0.6 Mpa, and having a GWP of 5 or less. The medical injectant composition according to Item 1. Item 3. The medical injectant composition according to Item 1 or 2, wherein the C2 olefin compounds include cis-1,2-difluoroethylene (HFO-1132(Z)). Section 4. A 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). Section 5 A medical propellant composition according to any one of claims 1 to 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. Section 6 A medical propellant composition according to any one of claims 1 to 5, comprising 70% by mass or more of the propellant with respect to the entirety of the medical propellant composition. [Effects of the Invention]

[0006] A new low-GWP medical propellant will be offered. [Modes for carrying out the invention]

[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 The propellant of this disclosure may further contain, in addition to C2 olefin compounds, 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. As for the additional compounds, Examples of "fluorocarbon compounds" include hydrofluoroolefins (HFOs), hydrochlorofluoroolefins (HCFOs), chlorofluorocarbons (CFCs), hydrochlorofluorocarbons (HCFCs), and hydrofluorocarbons (HFCs). Examples include R32, HFC-143a, HFC-134a, HFO-1243zf, HFC-245cb, HCFC-1122, HCFC-124, CFC-1113, and 3,3,3-trifluoropropine. Examples of "fluorine-free organic compounds" include propane (R290), propylene (R1270), butane (R600), isobutane (R600a), acetylene, and methylamine. When 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.

[0014] 1.3 Azeotropic or azeotropic propellant When the medical injection composition of the present disclosure is used in combination with an active ingredient, it is preferable that a substantially constant amount of the active ingredient can be injected regardless of the number of injections. Therefore, when the injection agent of the present disclosure is a mixture, it is preferably azeotropic or azeotrope-like. When the injection agent is an azeotropic or azeotrope-like mixture, the component ratio of the injection agent in the residual liquid hardly changes regardless of the number of injections, so a substantially constant amount of the active ingredient can be injected. The combination of C2 olefin compounds and additional compounds that becomes azeotropic or azeotrope-like is not particularly limited, but it preferably has a boiling point close to that of conventionally used medical injection agents and a vapor pressure at 20 °C, that is, 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. As a combination that satisfies the above conditions and further has a GWP of 5 or less, for example, an injection agent having a weight ratio of HFO-1132(Z):R1234zeE = 48:52 to 54:46, or an injection agent having a weight ratio of HFO-1132(Z):R600a = 75:25 to 81:19 can be mentioned.

[0015] The injection agent of the present disclosure may further contain other components in addition to the C2 olefin compounds and additional compounds, as long as the above characteristics and effects are not impaired. In this regard, it is preferable that the injection agent of the present disclosure contains 99.5 mass% or more, more preferably 99.75 mass% or more, and even more preferably 99.9 mass% or more of the total of the C2 olefin compounds and additional compounds with respect to the entire injection agent.

[0016] 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.

[0017] 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.

[0018] 1.5 additives The medical propellant composition disclosed herein 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, and pH adjusters. Furthermore, it 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 can be incorporated. 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. [Examples]

[0019] 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.

[0020] Example 1 Table 1 shows the GWP, boiling point, and vapor pressure at 20°C for each medical propellant-containing composition. GWP was assessed based on the values ​​(100-year values) from the IPCC (Intergovernmental Panel on Climate Change) 45th Assessment Report (AR4). For HFO-1132(E), which is not listed in AR4, the GWP was set to 1 or less, based on the <<1 indication in WMO (World Meteorological Organization) GAW Report No. 278 (2022). For HFO-1132(Z), the GWP was set to 1 or less, based on the GWP of HFO-1132(E). For HFO-1123, the GWP was set to 1 or less, based on the 0.3 value listed in WO2015 / 141678.

[0021] 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.

[0022] [Table 1]

[0023] Example 2 Table 2 shows the GWP, boiling point, and vapor pressure at 20°C for azeotropic compositions containing HFO-1132(Z) and additional compounds. The evaluation method is the same as in Example 1.

[0024] All of the compositions have low GWP (Global Warming Potential) and possess boiling points and vapor pressures at 20°C that are similar to those of conventionally used medical propellants, indicating their usefulness as substitutes for conventional medical propellants.

[0025] [Table 2]

[0026] Example 3 Table 3 shows the solubility of salbutamol, one of the active ingredients, in compositions containing the propellant of this disclosure. Solubility was calculated using the thermodynamic property estimation software "COSMOtherm" from Molsys Co., Ltd.

[0027] 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.

[0028] [Table 3]

Claims

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

2. The propellant is Its boiling point is between -28°C and -15°C. The vapor pressure at 20°C is 0.35 MPa to 0.6 MPa, and A medical propellant composition according to claim 1, wherein the GWP is 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. Furthermore, it contains an active ingredient, and the said active ingredient is The composition according to claim 4, comprising fluticasone, mometasone, beclomethasone, ciclesonide, budesonide, salbutamol, glycopyrrolate, formoterol, alformoterol, bambuterol, clenbuterol, salmeterol, indacaterol, orodaterol, vilanterol, and tiotropium, and pharmaceutically acceptable salts and derivatives thereof, selected from the group.

6. The medical propellant composition according to claim 4, comprising 70% by mass or more of the propellant with respect to the total amount of the medical propellant composition.

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