WO2023120703A1

WO2023120703A1 - Ocular instillation member

Info

Publication number: WO2023120703A1
Application number: PCT/JP2022/047635
Authority: WO
Inventors: 幸博矢野; 真黒木; 孝史塚谷; 彩子佐々木; 秀和三橋; 武志狩野
Original assignee: 大成化工株式会社; 株式会社プライムポリマー
Priority date: 2021-12-24
Filing date: 2022-12-23
Publication date: 2023-06-29

Abstract

Provided is an ocular instillation member including at least one component selected from an ocular instillation container main body and an ocular instillation nozzle, in which the ocular instillation container main body has a bottom part, a hollow cylindrical body part that is continuous to a circumferential edge of the bottom part, a shoulder part that is continuous to the body part, and an opening cylindrical part that is continuous to the shoulder part, each of the ocular instillation container main body and the ocular instillation nozzle contains a propylene-based polymer, and the formula (1) is satisfied.　x1-x2 ≦ 60.0 mg · · · (1) [In the formula, x1 represents the mass (mg) of a dried product produced by cutting out a test specimen having a weight of 5.0 g from the body part of the ocular instillation container main body or the ocular instillation nozzle, then cutting the test specimen into a piece having a size of 3 cm × 0.3 cm, then placing the cut piece in a round-bottomed flask containing 50 mL of n-hexane, then heating the resultant solution to reflux for 4 hours, then cooling the solution to room temperature to produce a solution, then filtrating the solution to produce a filtrate, then placing the filtrate in an evaporation pan, then drying the filtrate in a water bath, and then drying the resultant product at 105°C for 2 hours; and x2 represents the mass (mg) of a dried product produced by performing a blank test in the same manner as mentioned above except that the test specimen is not used.]

Description

eyedropper

One embodiment of the present invention relates to an eyedropper.

Conventionally, resin-made eyedrops have been known as eyedroppers because they are hard to break and can be administered dropwise to the eyeball by pressing (squeezing) the container body. .

For example, Patent Document 1 describes that blow-moldable thermoplastic resins such as polyethylene, polypropylene, polyethylene terephthalate, etc., can be mentioned as materials constituting the eyedropper.

Japanese Patent Application Laid-Open No. 2009-165680

When applying for manufacturing and marketing of ophthalmic solutions, it is necessary to consider various physical properties of the ophthalmic components that store and store the ophthalmic solutions, especially the body of the eyedropper container that is always in contact with the ophthalmic solution and the eyedropper nozzle that is in contact with the ophthalmic solution when the eyedrops are instilled. are required to be satisfied, and these required physical properties are often determined independently in each country.

As described above, propylene-based polymer eyedrops have been known in the past, and the propylene-based polymer eyedrops have satisfied most of the physical properties described above. standards are becoming stricter. In addition, some countries have higher standards for required physical properties, and in China's YBB regulations (YBB00072002: polypropylene eyedropper container), the amount of components eluted from the eyedropper into n-hexane (hereinafter referred to as "n-hexane non-volatile However, conventional propylene-based polymer eyedrops contain a large amount of n-hexane non-volatile matter, and in this respect, the physical properties required above cannot be satisfied. I found out.

One embodiment of the present invention provides an eyedropper with a low amount of n-hexane non-volatile matter.

As a result of earnest research, the inventors of the present invention completed an embodiment of the present invention with the following configuration example.
A configuration example of the present invention is as follows.

[1] An eyedropper member including at least one selected from an eyedropper container body and an eyedropper nozzle,
The eye drop container main body has a bottom portion, a hollow cylindrical body portion continuing to the periphery of the bottom portion, a shoulder portion continuing to the body portion, and an open cylindrical portion continuing to the shoulder portion,
An eyedropper, wherein the eyedropper container body and the eyedropper nozzle contain a propylene-based polymer and satisfy the following formula (1).
x1−x2≦60.0 mg (1)
[x1 is a 5.0 g test piece cut from the body of the eyedropper body or from the eyedropper nozzle, cut into a size of 3 cm × 0.3 cm, and then filled with 50 mL of n-hexane. Place in a bottom flask, heat under reflux for 4 hours, cool to room temperature, filter the resulting liquid, put the resulting filtrate in an evaporating dish, dry in a water bath, and then heat at 105°C. is the mass (mg) of the dried product obtained by drying for 2 hours at x2 is the mass (mg) of the dried body obtained by performing the blank test in the same manner as above, except that the test piece was not used. ]

[2] The eye drop according to [1], wherein the propylene-based polymer contains 2.5% by mass or less of a component having a molecular weight of 10000 or less as measured by gel permeation chromatography (GPC). Element.

[3] The eyedropper according to [1] or [2], wherein the propylene-based polymer is a copolymer of propylene and a monomer other than propylene, and the monomer other than propylene contains ethylene.

[4] The content of ethylene-derived structural units in the propylene-based polymer is 4.0% by mass or less with respect to 100% by mass of all structural units constituting the propylene-based polymer, according to [3]. Eyedropper.

[5] The eye drop according to any one of [1] to [4], wherein the propylene-based polymer has a melt flow rate (230°C, 2.16 kg load) of 0.1 to 30.0 g/10 minutes. Element.

[6] The eyedropping member according to any one of [1] to [5], which contains the propylene-based polymer and a crystal nucleating agent.
[7] The eyedropping member according to [6], wherein the eyedropping member is an eyedropping nozzle.

[8] The eyedropping member according to any one of [1] to [7], wherein the eyedropping member has a density of 0.900 to 0.915 g/cm ³ .

According to one embodiment of the present invention, it is possible to provide an eyedropper with a small amount of n-hexane non-volatile matter.

FIG. 1 is an external perspective view showing an example of an eye drop container in which an eye drop nozzle is fitted to an eye drop container main body according to one embodiment of the present invention. FIG. 2 is a cross-sectional explanatory view showing an example of an eye drop container in which an eye drop nozzle is fitted to an eye drop container main body according to one embodiment of the present invention. FIG. 3 is a cross-sectional explanatory view showing an example of a capped eyedrops container having an eyedrops container main body, an eyedrops nozzle, and a cap according to one embodiment of the present invention.

≪Eye drops≫
An eyedropping member according to an embodiment of the present invention includes at least one selected from an eyedropping container main body (hereinafter also referred to as "this container main body") and an eyedropping nozzle (hereinafter also referred to as "this nozzle"), and the present invention Specifically, the eye drop member according to one embodiment of is the present container main body, the present nozzle, or the present container main body and the present nozzle.
The container body has a bottom portion, a hollow cylindrical body portion continuing to the periphery of the bottom portion, a shoulder portion continuing to the body portion, and an open cylindrical portion continuing to the shoulder portion.
The container main body and the nozzle contain a propylene-based polymer and satisfy the following formula (1).
x1−x2≦60.0 mg (1)
[x1 is a 5.0 g test piece cut from the trunk of the container body or from the nozzle, cut the test piece to a size of 3 cm x 0.3 cm, and then a circle containing 50 mL of n-hexane Place in a bottom flask, heat under reflux for 4 hours, cool to room temperature, filter the resulting liquid, put the resulting filtrate in an evaporating dish, dry in a water bath, and then heat at 105°C. is the mass (mg) of the dried product obtained by drying for 2 hours at x2 is the mass (mg) of the dried body obtained by performing the blank test in the same manner as above, except that the test piece was not used. ]

The left side of the formula (1) represents the amount of n-hexane non-volatile matter.
The right side of the formula (1) is 60.0 mg, preferably 50 mg, more preferably 40 mg.
The eyedropper body and the eyedropper nozzle that satisfy the formula (1) can be said to be the eyedropper body and the eyedropper nozzle having a small amount of n-hexane non-volatile matter. Since the amount of components eluted from the main body and the eyedropper nozzle into the eyedrops is reduced and the contamination of the eyedrops is reduced, safe eyedrops can be provided over a long period of time.

<Propylene polymer>
The container body and the nozzle contain a propylene-based polymer. That is, the main body of the container is an eye drop container main body made of a propylene polymer, and the nozzle is an eye drop nozzle made of a propylene polymer.
The propylene-based polymer contained in the container main body and the nozzle may be of one type or two or more types.

A polypropylene-based polymer is a polymer whose main component is a structural unit derived from propylene, and specific examples thereof include homopolymers of propylene (propylene homopolymers), (propylene copolymer). Among these, a propylene homopolymer is preferable from the viewpoint that an eye drop container body having a small amount of n-hexane non-volatile matter can be easily obtained, and an eye drop container body excellent in moldability and transparency can be easily obtained. A propylene copolymer is preferred because it can be A propylene copolymer is more preferable from the viewpoint that it is possible to easily obtain an eye drop container main body that is excellent in balance between excellent moldability and transparency and a low n-hexane non-volatile matter content.

The stereoregularity of the polypropylene-based polymer is not particularly limited, and the propylene copolymer may be a random copolymer or a block copolymer. preferable.

Examples of the other monomers include ethylene and α-olefins having 4 to 20 carbon atoms. Examples of α-olefins having 4 to 20 carbon atoms include 1-butene, 1-pentene, 3-methyl-1-butene, 1-hexene, 4-methyl-1-pentene, 3-methyl-1-pentene, 1-octene, 1-decene, 1-dodecene, 1-tetradecene, 1-hexadecene, 1-octadecene and 1-eicosene.
As the other monomer, ethylene, 1-butene, 1-hexene and 4-methyl-1-pentene are preferable, and ethylene is more preferable.
1 type(s) or 2 or more types can be used for said other monomer.

The content of constituent units derived from other monomers in the propylene copolymer is set to It is preferably 4.0% by mass or less, more preferably 3.8% by mass or less, and still more preferably 3.5% by mass or less relative to 100% by mass of the structural units. It is 0% by mass.

The content ratio of components having a molecular weight of 10,000 or less as measured by gel permeation chromatography (GPC) in the propylene-based polymer is as follows: It is preferably 2.5% by mass or less, more preferably 2.0% by mass or less, and still more preferably 1.5% by mass or less, and the lower limit is not particularly limited. It is also preferred to be free of ingredients.
Specifically, the content of the component having a molecular weight of 10,000 or less can be measured by the method described in Examples below.

The melt flow rate (MFR) of the propylene-based polymer, measured according to ASTM D-1238 (measurement temperature: 230°C, load: 2.16 kg), is excellent in moldability, especially injection moldability, into eye drop container bodies. etc., preferably 0.1 g/10 min or more, more preferably 0.3 g/10 min or more, preferably 30.0 g/10 min or less, more preferably 8.0 g/10 min or less, especially It is preferably 4.0 g/10 minutes or less.

The tensile elastic modulus of the propylene-based polymer measured in accordance with JIS K 6921-2:2018 is preferably 700 MPa or more, more preferably 700 MPa or more, more preferably from the viewpoint of easily obtaining an eye drop container body having excellent mechanical strength. It is 900 MPa or more, preferably 2400 MPa or less, more preferably 1700 MPa or less.

[Method for Producing Propylene Polymer]
The propylene-based polymer can be produced by polymerizing propylene or propylene and the other monomers by a known polymerization method such as slurry polymerization or bulk polymerization. In this production, it is preferable to use a polypropylene production catalyst, which will be described later.

Preferred examples of conditions for producing a propylene polymer include a polymerization temperature of preferably 20 to 80° C., more preferably 40 to 80° C., and a polymerization pressure of generally normal pressure to 9.8 MPa, preferably 0.2 to 80° C.; 4.9 MPa and conditions in which hydrogen is present as a molecular weight modifier.

<Catalyst for polypropylene production>
The polypropylene production catalyst comprises, for example, a transition metal catalyst component having magnesium, titanium and halogen as essential components, an organometallic compound catalyst component such as an organoaluminum compound, and an electron-donating compound catalyst component such as an organosilicon compound. Catalysts obtained by using these compounds are mentioned, and typical examples thereof include the following catalysts.

(Transition metal catalyst component)
Examples of the transition metal catalyst component include (i) a transition metal catalyst component having a carrier and (ii) a transition metal catalyst component having no carrier.

(i) Transition Metal Catalyst Component Having Carrier The carrier is preferably a carrier obtained from metallic magnesium, an alcohol, and a halogen and/or a halogen-containing compound.

As metal magnesium, granular, ribbon-like, powdered magnesium, and the like can be used. Metal magnesium is preferably not coated with magnesium oxide or the like on its surface.
1 type(s) or 2 or more types can be used for metallic magnesium.

As the alcohol, it is preferable to use a lower alcohol having 1 to 6 carbon atoms. In particular, when ethanol is used, it is possible to easily obtain a carrier that remarkably improves the expression of catalytic performance. The amount of alcohol to be used is preferably 2 mol or more, more preferably 5 mol or more, and preferably 100 mol or less, more preferably 50 mol or less, relative to 1 mol of metallic magnesium.
1 type(s) or 2 or more types can be used for alcohol.

Halogen is preferably chlorine, bromine or iodine, preferably iodine. Moreover, as the halogen-containing compound, MgCl ₂ and MgI ₂ are preferable. The amount of the halogen or halogen-containing compound used is usually 0.0001 gram-atom or more, preferably 0.0005 gram-atom or more, and more preferably 0.0005 gram-atom or more of the halogen atom or the halogen atom in the halogen-containing compound per 1 gram atom of metallic magnesium. It is preferably 0.001 gram-atom or greater.
Halogens and halogen-containing compounds can be used alone or in combination of two or more.

A method of obtaining a carrier by reacting metallic magnesium, an alcohol, and a halogen and/or a halogen-containing compound includes, for example, metallic magnesium, an alcohol, a halogen and/or a halogen-containing compound, under reflux (e.g., about 79° C.) until generation of hydrogen gas is no longer observed (usually for 20 to 30 hours). The reaction is preferably carried out in an inert gas atmosphere such as nitrogen gas or argon gas.

When the obtained carrier is used for synthesizing a transition metal catalyst component, it may be dried or washed with an inert solvent such as heptane after filtration.
It is preferable that the obtained carrier be nearly granular and have a sharp particle size distribution. Furthermore, it is preferable that the variation in the particle size of each particle is small. In this case, the sphericity (S) represented by the following formula (I) is less than 1.60, particularly less than 1.40, and the particle size distribution index (P) represented by the following formula (II) is preferably less than 5.0, especially less than 4.0.

S=(E1/E2) ² (I)
In formula (I), E1 represents the projected contour length of the carrier particle, and E2 represents the perimeter of a circle equal to the projected area of the carrier particle.

P=D90/D10 (II)
In formula (II), D90 refers to the particle diameter corresponding to a mass cumulative fraction of 90%. That is, it indicates that the sum of the mass of particles smaller than the particle diameter represented by D90 is 90% of the total mass of all particles. D10 refers to the particle diameter corresponding to a mass cumulative fraction of 10%.

The transition metal catalyst component having the carrier can usually be obtained by contacting the carrier with at least a titanium compound. The contact with the titanium compound may be performed in multiple steps. Examples of titanium compounds include titanium compounds represented by the following formula (III).

^TiX1n ⁽ _OR1 ) _4-n (III)
In formula (III), X ¹ is independently a halogen atom, particularly preferably a chlorine atom, R ¹ is independently a hydrocarbon group having 1 to 10 carbon atoms, preferably a linear or branched alkyl group, When there are a plurality of X ¹ , they may be the same or different, and when there are a plurality of R ¹ , they may be the same or different, and n is an integer of 0-4.

Specific examples of titanium compounds include Ti(Oi-C ₃ H ₇ ) ₄ , Ti(O-C ₄ H ₉ ) ₄ , TiCl(O-C ₂ H ₅ ) ₃ , TiCl(Oi —C ₃ H ₇ ) ₃ , TiCl(O—C ₄ H ₉ ) ₃ , TiCl ₂ (O—C ₄ H ₉ ) ₂ , TiCl ₂ (Oi-C ₃ H ₇ ) ₂ , TiCl _{4 .} , TiCl ₄ are preferred.
1 type(s) or 2 or more types can be used for a titanium compound.

The transition metal catalyst component having the carrier can usually be obtained by contacting the carrier with an electron-donating compound. Electron-donating compounds include, for example, di-n-butyl phthalate.
1 type(s) or 2 or more types can be used for an electron-donating compound.

When the titanium compound and the electron-donating compound are brought into contact with the carrier, a halogen-containing silicon compound such as silicon tetrachloride can be brought into contact.
Halogen-containing silicon compounds can be used alone or in combination of two or more.

The transition metal catalyst component having the carrier can be prepared by a known method. For example, there is a method of using an inert hydrocarbon such as pentane, hexane, peptane or octane as a solvent, adding the carrier, the electron donating compound and the halogen-containing silicon compound to the solvent, and then adding the titanium compound while stirring. mentioned.

Usually, 0.01 to 10 mol, preferably 0.05 to 5 mol of the electron donating compound is added to 1 mol of the support in terms of magnesium atom, and the titanium compound is added to 1 mol of the support in terms of magnesium atom. 1 to 50 mol, preferably 2 to 20 mol, is added, and the contact reaction is performed at 0 to 200 ° C. for 5 minutes to 10 hours, preferably at 30 to 150 ° C. for 30 minutes to 5 hours. You can do it.
After completion of the reaction, it is preferable to wash the produced transition metal catalyst component using an inert hydrocarbon such as n-hexane or n-heptane.

(ii) Transition Metal Catalyst Component Not Having a Carrier The transition metal catalyst component not having a carrier is a component obtained by contacting a liquid magnesium compound and a liquid titanium compound in the presence of an electron donating compound. may be The contact with the liquid titanium compound may be carried out in multiple times.

A liquid magnesium compound can be obtained, for example, by contacting a known magnesium compound and an alcohol, preferably in the presence of a liquid hydrocarbon medium, to liquefy.
1 type(s) or 2 or more types can be used for a liquid magnesium compound.

Examples of the magnesium compound include magnesium halides such as magnesium chloride and magnesium bromide.
Examples of the alcohol include aliphatic alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, and 2-ethylhexyl alcohol.
Examples of the liquid hydrocarbon medium include hydrocarbon compounds such as heptane, octane, and decane.
The amount of alcohol used in preparing the liquid magnesium compound is generally 1.0 to 25 mol, preferably 1.5 to 10 mol, per 1 mol of the liquid magnesium compound.

Examples of liquid titanium compounds include titanium compounds represented by the formula (III).
1 type(s) or 2 or more types can be used for a liquid titanium compound.

The amount of the liquid titanium compound used is usually 0.1 to 1000 mol, preferably 1 to 200 mol, per 1 mol of magnesium atoms (Mg) contained in the liquid magnesium compound.

Examples of electron-donating compounds include dicarboxylic acid ester compounds such as phthalates, acid anhydrides such as phthalic anhydride, organosilicon compounds such as dicyclopentyldimethoxysilane, dicyclohexyldimethoxysilane, cyclohexylmethyldimethoxysilane, and polyethers. , acid halides, acid amides, nitriles, and organic acid esters.
1 type(s) or 2 or more types can be used for an electron-donating compound.

The amount of the electron-donating compound to be used is usually 0.01 to 5 mol, preferably 0.1 to 1 mol, per 1 mol of magnesium atoms (Mg) contained in the liquid magnesium compound.
The contact temperature is usually -70 to 200°C, preferably 10 to 150°C.

(organometallic compound catalyst component)
As the organometallic compound catalyst component, an organoaluminum compound is preferable. Examples of organoaluminum compounds include compounds represented by the following formula (IV).

^AlR2nX23 ^- _n ₍ IV)
In formula (IV), R ² is independently an alkyl group having 1 to 10 carbon atoms, a cycloalkyl group or an aryl group, X ² is independently a halogen atom or an alkoxy group, and a chlorine atom or a bromine atom is Preferably, when multiple R ² are present, they may be the same or different, and when multiple X ² are present, they may be the same or different, and n is a number from 1 to 3.

Specific examples of organoaluminum compounds include trialkylaluminum compounds such as trimethylaluminum, triethylaluminum and triisobutylaluminum, diethylaluminum monochloride, diisobutylaluminum monochloride, diethylaluminum monoethoxide, and ethylaluminum sesquichloride. be done.
1 type(s) or 2 or more types can be used for an organoaluminum compound.

The amount of the organometallic compound catalyst component used is usually 0.01 mol or more, preferably 0.05 mol or more, and usually 20 mol or less, preferably 10 mol, per 1 mol of the titanium atom in the transition metal catalyst component. It is below.

(Electron donating compound catalyst component)
An organosilicon compound is preferable as the electron-donating compound catalyst component. Examples of organosilicon compounds include dicyclopentyldimethoxysilane, cyclohexylmethyldimethoxysilane, diethylaminotriethoxysilane, diisopropyldimethoxysilane, and cyclohexylisobutyldimethoxysilane.
1 type(s) or 2 or more types can be used for an organosilicon compound.

The amount of the electron-donating compound catalyst component used is usually 0.01 mol or more, preferably 0.1 mol or more, and usually 20 mol or less, preferably 5 mol, per 1 mol of the titanium atom in the transition metal catalyst component. less than a mole.

(Preprocessing)
The polypropylene production catalyst is preferably used for polymerization after pretreatment such as prepolymerization.
As a method for the pretreatment, for example, an inert hydrocarbon such as pentane, hexane, peptane, and octane is used as a solvent, and the solvent contains the transition metal catalyst component, the organometallic compound catalyst component, and, if necessary, A method of charging an electron-donating compound catalyst component, supplying propylene while stirring, and allowing the reaction to occur can be used.
Propylene is preferably fed under a partial pressure of propylene higher than atmospheric pressure and pretreated at 0-100° C. for 0.1-24 hours.
After completion of the reaction, it is preferable to wash the pretreated material with an inert hydrocarbon such as n-hexane or n-heptane.

<Other ingredients>
In addition to the propylene-based polymer, the main body of the container and the nozzle may contain stabilizers such as antioxidants, heat stabilizers, light stabilizers, and weather stabilizers, dispersants, fillers, crystal nucleating agents, etc., if necessary. Other components that have been used in the conventional eyedropper container body and eyedropper nozzle may be contained within a range that does not impair the effects of the present invention.
The present container body and the present nozzle may each contain one type of these other components alone, or may contain two or more types thereof.

Whether or not the main body of the container and the nozzle contained the above-mentioned other components, the amount of n-hexane non-volatile matter was well below the standard value. Therefore, the contents of the other components in the container main body and the nozzle are not particularly limited, but are preferably 0.30% by mass or less, more preferably 0.25% by mass or less.

Chinese YBB regulations require that the density of the container body and the nozzle be in the range of 0.900 to 0.915 g/cm ³ . In order to satisfy this YBB regulation, it is preferable that the density of the present container body and the present nozzle also be in the range of 0.900 to 0.915 g/cm ³ .

The density is calculated by the following formula (2).
Density=Wa×d/(Wa−Ws) (2)
[Wa (g) is obtained by cutting a 2 g test piece from the barrel of the container body or from the nozzle, placing the test piece in a round-bottomed flask containing 100 mL of pure water, heating under reflux for 2 hours, and then It is the mass of the test piece obtained by drying the test piece cooled to room temperature at 80° C. for 2 hours. Ws (g) is the mass of the test piece immersed in a liquid having a density of d (g/cm ³ ) and immersed in the liquid. ]

From the point of view that the container body and/or the nozzle having the density can be easily obtained, the container body and/or the nozzle are composed of one or more propylene-based polymers and one or more Two or more kinds of crystal nucleating agents may be contained, and the present nozzle preferably contains one or two or more kinds of the propylene-based polymer and one or two or more kinds of crystal nucleating agents.
Examples of the crystal nucleating agent include inorganic fillers such as silica, talc, and calcium carbonate, sodium benzoate, aluminum benzoate, aluminum dibenzoate, potassium benzoate, lithium benzoate, sodium β-naphthalate, sodium cyclohexane carboxy benzylidene sorbitol and its derivatives, carboxylic acid metal salts such as phosphate metal salts, pimelate metal salts, rosin acid metal salts, stearate metal salts, 2-hydroxy-2-oxo-4,6,10,12 - sodium salt of tetra-tert-butyl-1,3,2-dibenzo[d,g]perhydrodioxaphosphalosine, polymer (e.g. poly-3-methylbutene-1, polyvinylcycloalkane, polyvinyltrialkylsilane , EPR, Kevlar fiber, 2,2′-methylenebis(4,6-di-tert-butylphenyl)sodium phosphate, polyol derivatives, and amide compounds.

When the container body and/or the nozzle contain the propylene-based polymer and the crystal nucleating agent, the amount of the crystal nucleating agent used relative to 100 parts by mass of the propylene-based polymer is / Or it is preferably 700 ppm or more, more preferably 900 ppm or more, preferably 3000 ppm or less, and more preferably 2500 ppm or less from the viewpoint that the present nozzle can be easily obtained.

<Structure, etc. of this container body and this nozzle>
The main body of the container has a bottom, a hollow cylindrical trunk connected to the periphery of the bottom, a shoulder connected to the trunk, and an open cylinder connected to the shoulder, and contains an ophthalmic solution. There is no particular limitation as long as the eye drop container main body is possible, and conventionally known structures can be used.
A specific example of such a main container body is the container main body 1 shown in FIGS.
Further, the nozzle is not particularly limited as long as it can drop the container body, particularly the ophthalmic solution (medical solution) contained in the container body, and may have a conventionally known configuration.
Specific examples of such a present nozzle include the eyedropper nozzle 2 and the eyedropper nozzle 3 shown in FIGS.

FIG. 1 is an external perspective view showing an example of an eye drop container in which an eye drop nozzle is fitted to one embodiment of the container main body, and FIG. 2 is an explanatory cross-sectional view of the eye drop container.
A container body (main container body) 1 in FIG. , and an opening cylindrical portion 11 in which is formed.

An eyedropper nozzle 2 (main nozzle) for liquid injection is fitted into the opening cylindrical portion 11 in FIG.
The eyedropper nozzle 2 includes a circular plate portion 21, an outer cylinder portion 22 integral with the circular plate portion 21 and hanging down from the periphery of the circular plate portion 21, an inner cylinder portion 23 hanging down from the lower surface of the circular plate portion 21, It is roughly composed of a cylindrical liquid injection part 24 protruding from the upper surface of a circular plate part 21, and the opening cylinder part 11 of the container body 1 is fitted into the gap between the outer cylinder part 22 and the inner cylinder part 23. there is A liquid injection port 25 is formed at the tip of the liquid injection portion 24, and a liquid passage portion 26 through which the ophthalmic solution extruded from the container body 1 passes is formed to extend from the liquid injection port 25 to the lower surface of the circular plate portion 21. ing.

The container body 1 in FIG. 1 is normally used as an eyedrop container with a cap by screwing a cap (not shown) onto the opening cylindrical portion 11 of the container body 1 . The cap may be formed with a protrusion that closes the injection port 25 when the cap is attached.

FIG. 3 is a cross-sectional explanatory view of a capped eye drop container having a container body (main container body) 1, an eye drop nozzle (main nozzle) 3, and a cap 221. As shown in FIG.
The capped eye drop container in FIG. 3 includes a container body 1 loaded with a predetermined amount (eg, 5 mL) of an eye drop (medicine) Y, an eye drop nozzle 3 attached to an opening cylindrical portion 11 of the container body 1, and a cap 221 that is screwed into the opening cylindrical portion 11 to protect the eye drop nozzle (dripping nozzle) 3 .

The container body 1 in FIG. 3 includes a bottom portion 12, a hollow tubular (bottle-shaped) body portion 13 connected to the periphery of the bottom portion 12, a shoulder portion 14 continuing to the body portion 13, and a shoulder portion continuing to the shoulder portion. and an open cylindrical portion 11 having a threaded portion formed on its outer peripheral surface.

The eyedropper nozzle 3 is roughly composed of a collar portion 33, an outer wall 44 that is integral with the collar portion 33 and hangs down from the bottom surface of the collar portion 33, and a columnar liquid injection portion 32 that protrudes from the top surface of the collar portion 33, The outer surface of the outer wall 44 and the inner surface of the opening cylindrical portion 11 of the container body 1 are tightly fitted together. A liquid injection port 312 is formed at the tip of the liquid injection section 32 , and an inlet section 311 is formed at the lower end of the liquid injection section 32 . A liquid passing portion 31 through which the ophthalmic solution extruded from the container body 1 passes is formed from the liquid inlet 312 to the inlet. The liquid passage portion 31 is set so that the inner diameter near the inlet portion 311 is sharply reduced.

The cap 221 has a threaded portion on its inner peripheral surface that can be attached and detached by screwing it into the threaded portion on the outer peripheral surface of the opening tube portion 11, and its upper inner surface is fitted into the tip opening of the liquid injection port 312 of the eyedropper nozzle 3 to seal it. A convex portion 222 is formed that can The cap 221 closes the injection port 312 with the convex portion 222 in the closed state (the state shown in FIG. 3) screwed into the opening cylindrical portion 11, and the upper surface of the collar portion 33 and the screw portion are closed. The inside of the container main body 1 can be sealed by closely contacting with one or more locations.

1 and 2 show a structure in which the eyedropper nozzle 2 and the container body 1 are separate bodies, and FIG. 3 shows a structure in which the eyedropper nozzle 3 and the container body 1 are separate bodies. However, both may be molded integrally. In this case, the filling of the ophthalmic solution Y contained in the container body 1 and the molding of the container body may be performed at the same time.

The size of the container body is not particularly limited, and it may be designed to have a volume capable of being filled with 1 to 20 mL of the ophthalmic solution. The height is, for example, 20-40 mm.
The average thickness of the trunk is, for example, 0.4 to 1.0 mm.
The shape of the bottom is not particularly limited, but may be, for example, circular (including elliptical, oval, etc.), polygonal (including rectangular, rhombic, pentagonal, hexagonal, etc.).
The diameter of the injection port may be appropriately set according to the properties of the ophthalmic solution, and is not particularly limited, but is usually designed in the range of 1 to 4 mm.

The material constituting the cap is not particularly limited, and materials that have been used for conventionally known caps can be used. Examples thereof include injection-moldable thermoplastic resins such as polyethylene, polypropylene, and polyethylene terephthalate. . It is also possible to use the same material as the container body and the eye drop nozzle.

The manufacturing method of the present container body, the eye drop nozzle, and the cap is not particularly limited, and may be manufactured by a conventionally known manufacturing method. , injection molding, direct blow molding, especially injection blow molding.

Hereinafter, one embodiment of the present invention will be described in more detail with examples, but the present invention is not limited by these.

The physical properties of the propylene-based polymer used in the tests below were measured as follows. Table 1 shows the results.

<Content ratio of components having a molecular weight of 10,000 or less>
The content of components having a molecular weight of 10,000 or less in the propylene-based polymer used in the following tests was measured by GPC under the following measurement conditions.
(Measurement condition)
Liquid chromatograph: (manufactured by Waters, Alliance/GPC2000 type)
Column: Two TSKgelGMH ₆ -HT and two TSKgelGMH ₆ -HTL (manufactured by Tosoh Corporation, column size: 7.5 mm in diameter and 300 mm in length) connected in series Mobile phase medium: o - dichlorobenzene (containing 0.025% by weight of dibutylhydroxytoluene (BHT))
Sample concentration: 0.15% (V/W)
Flow rate: 1.0 ml/min Column temperature: 140°C

The obtained chromatogram is analyzed by a known method using data processing software Empower 2 manufactured by Waters, using a calibration curve using a standard polystyrene sample (manufactured by Tosoh Corporation). The content ratio (% by mass) of components having a molecular weight of 10,000 or less in the propylene-based polymer was calculated.

<Ethylene content>
The ethylene content in the propylene-based polymer used in the following tests was measured by ¹³ C-NMR under the following measurement conditions.
(Measurement condition)
Measurement device: LA400 type nuclear magnetic resonance device manufactured by JEOL Ltd. Measurement mode: BCM (Bilevel Complete decoupling)
Observation frequency: 100.4MHz
Observation range: 17006.8Hz
Pulse width: C nucleus 45° (7.8 μs)
Pulse repetition time: 5 seconds Sample tube: 5 mmφ
Sample tube rotation speed: 12 Hz
Accumulation times: 20000 times Measurement temperature: 125°C
Solvent: 1,2,4-trichlorobenzene; 0.35 ml/deuterated benzene; 0.2 ml
Sample amount: about 40 mg

<MFR>
The MFR of the propylene-based polymer used in the following tests was measured according to ASTM D-1238 (measurement temperature: 230°C, load: 2.16 kg).

<Tensile modulus>
The tensile elastic modulus of the propylene-based polymer used in the following tests was measured according to JIS K 6921-2:2018.

[Production Example 1]
<Preparation of transition metal catalyst component>
A vibration mill equipped with 4 pulverizing pots having an inner volume of 4 L each containing 9 kg of steel balls of 12 mm in diameter was prepared. 300 g of magnesium chloride, 115 mL of diisobutyl phthalate, and 60 mL of titanium tetrachloride were added to each pot in a nitrogen atmosphere, and the mixture was pulverized for 40 hours to obtain a co-pulverized product.
75 g of the obtained co-ground material was placed in a 5 L flask, 1.5 L of toluene was added thereto, and the mixture was stirred at 114° C. for 30 minutes, then allowed to stand and the supernatant was removed. Then, 1.5 L of n-heptane was added three times at 20° C. to wash the solid content. After that, 1.5 L of n-heptane was further added to disperse the solid content, thereby obtaining a slurry-like transition metal catalyst component. The resulting transition metal catalyst component contained 2.3% by mass of titanium and 18% by mass of diisobutyl phthalate.

<Production of prepolymerization catalyst>
100 g of the transition metal catalyst component, 15.4 mL of triethylaluminum, and 100 L of heptane were placed in a 200 L autoclave equipped with a stirrer, 600 g of propylene was added while maintaining the internal temperature at 5° C., and the mixture was reacted with stirring for 60 minutes. After completion of the polymerization, 4.1 mL of titanium tetrachloride was charged to obtain a prepolymerized catalyst. This prepolymerized catalyst contained 6 g of polypropylene per 1 g of transition metal catalyst component.

<Production of propylene-based polymer 1>
100 kg/hour of propylene, 1.38 kg/hour of ethylene, 0.87 g/hour of prepolymerization catalyst, 3.4 mL/hour of triethylaluminum, and 4 parts of cyclohexylmethyldimethoxysilane were placed in a 500 L vessel polymerization vessel equipped with a stirrer. Hydrogen was supplied continuously at a rate of 2 mL/hour so that the hydrogen concentration in the gas phase was 0.13 mol %. The temperature of the vessel polymerization vessel was 70°C and the pressure was 3.0 MPa/G.
After the obtained slurry was deactivated, the propylene was evaporated to obtain a propylene-based polymer 1 in powder form. The obtained propylene-based polymer 1 had an MFR of 0.5 g/10 min and an ethylene content of 3.0% by mass.

[Production Examples 2 to 5] Production of propylene-based polymers 2 to 5 In the same manner as in Production Example 1, propylene System polymers 2-5 were prepared.

[Example 1]
Using the propylene-based polymer 1 (propylene/ethylene random copolymer) produced in Production Example 1 and having the physical properties shown in Table 1 below, an eye drop container having the shape shown in FIG. bottom. The container main body was produced by injection blow molding the propylene-based polymer 1 . The eye drop nozzle was produced by injection molding the propylene-based polymer 1.
The height of the produced container body was 42.7 mm, the height of the trunk was 29.5 mm, the average thickness of the trunk was 0.6 mm, and the shape of the bottom was oval. . Moreover, the inner diameter of the opening cylindrical portion was 8.1 mm.

[Example 2]
Example 1 was the same as Example 1, except that the propylene-based polymer 2 (propylene homopolymer) produced in Production Example 2 and having the physical properties shown in Table 1 below was used instead of the propylene-based polymer 1. Then, an eye drop container was produced.

[Comparative Example 1]
Example 1 except that the propylene-based polymer 3 (propylene/ethylene random copolymer) produced in Production Example 3 and having the physical properties shown in Table 1 below was used instead of the propylene-based polymer 1 in Example 1. An eye drop container was produced in the same manner as above.

[Comparative Example 2]
Example 1 except that the propylene-based polymer 4 (propylene/ethylene random copolymer) produced in Production Example 4 and having the physical properties shown in Table 1 below was used instead of the propylene-based polymer 1 in Example 1. An eye drop container was produced in the same manner as above.

[Comparative Example 3]
Example 1 except that the propylene-based polymer 5 (propylene-ethylene random copolymer) produced in Production Example 5 and having the physical properties shown in Table 1 below was used instead of the propylene-based polymer 1 in Example 1. An eye drop container was produced in the same manner as above.

<N-hexane non-volatile matter amount>
A 5.0 g test piece was cut from the body of the eye drop container body of the eye drop container prepared in Examples and Comparative Examples, cut into a size of 3 cm × 0.3 cm, and then diluted with 50 mL of n-hexane. placed in a round-bottomed flask and heated to reflux for 4 hours. After that, the liquid obtained by cooling to room temperature is filtered to obtain a filtrate, and the obtained filtrate is placed in an evaporating dish, dried in a water bath, and dried at 105 ° C. for 2 hours. Body mass x1 (mg) was measured.
A blank test was performed in the same manner as described above, except that the test piece was not used, and the mass x2 (mg) of the resulting dried body was measured.
Using the measured masses x1 and x2, the amount of n-hexane non-volatile matter was calculated from the following formula (3). Table 1 shows the results. The results in Table 1 are the average values of the n-hexane non-volatile matter amounts measured and calculated by conducting tests using 5 specimens of the eyedropper containers produced in each example and comparative example.
Amount of n-hexane non-volatile matter (mg) = x1-x2 (3)

<Dripping force>
The dropping force of the eyedropper prepared in Example 1 was measured as follows.
An eye drop container was filled with 5 mL of distilled water and an eye drop nozzle was capped. Next, with the mouth of the eye drop container facing directly downward, a load (dropping force, unit: N ) was measured.
As a result of measurement, the dropping force was 10.56N. The results are average values of dropping force measured by conducting tests using 5 specimens of the manufactured eyedrop container.
(Measurement condition)
Measurement environment: 23°C, 50% RH
Push speed: 0.2mm/s
Push position: Flat part of the body of the eyedropper body (near the center of the body of the eyedropper body)
Number of drops: 20 drops

<Transparency (haze value)>
The haze value of the body of the eye drop container body of the eye drop container produced in Example 1 was measured based on JIS K 7136:2000.
As a result of measurement, the haze value was 31.6%.

<Transpiration>
The transpiration property of the eyedropper prepared in Example 1 was measured as follows.
An eyedrop container was filled with 5 mL of distilled water, and the weight of the eyedrop container filled with distilled water was measured using an electronic balance (MSA225S-100-DI manufactured by Sartorius) to calculate the filling amount.
After that, the eyedropper was placed in a constant temperature and humidity bath (PR-1J manufactured by Espec Co., Ltd.) set at 40° C. and 25% RH, and stored for 12 hours. Next, the eyedropper was taken out from the constant temperature and humidity bath, and after slowly cooling at room temperature for 2 hours, the mass (initial mass) of the eyedropper was measured using an electronic balance (MSA225S-100-DI).
After that, the eyedropper was placed in a constant temperature and humidity bath (PR-1J) set at 40° C. and 25% RH, and stored for 6 days. Next, the eyedropper container was removed from the constant temperature and humidity bath, and after slowly cooling at room temperature for 2 hours, the weight of the eyedropper container (mass after 6 days) was measured using an electronic balance (MSA225S-100-DI).
After that, the eyedropper was placed in a constant temperature and humidity bath (PR-1J) set at 40° C. and 25% RH, and stored for 4 days. Next, the eyedropper container was removed from the constant temperature and humidity chamber, and after slowly cooling at room temperature for 2 hours, the weight of the eyedropper container (mass after 10 days) was measured using an electronic balance (MSA225S-100-DI).
When plotting the values of the initial mass, the mass after 6 days, and the mass after 10 days with the number of days elapsed on the horizontal axis and the mass of the eyedropper container on the vertical axis, the slope of the transpiration rate transition line is determined, and the transpiration rate transition line is obtained. was taken as the transpiration rate (mg/day).
As a result of measurement, the transpiration rate was 0.92 mg/day.

For the eyedropper container produced in Example 2, the dropping power, transparency and transpiration were measured in the same manner as in Example 1. As a result, the dropping force was 8.73 N, the haze value was 74.8%, and the transpiration rate was 0.91 mg/day.

From these results, it can be said that both the eye drop containers produced in Examples 1 and 2 can be used as eye drop containers.

[Example 3]
Using the propylene-based polymer 1 (propylene/ethylene random copolymer) produced in Production Example 1 and having the physical properties shown in Table 1, an eye drop nozzle having the shape shown in FIG. 3 was produced by injection molding.
The total height of the manufactured eye drop nozzle was 16.2 mm, the height of the liquid injection part was 6.5 mm, the height of the outer wall was 8.0 mm, and the outer diameter of the collar part was 10.6 mm. Moreover, the diameter of the injection port was 2.0 mm.

[Example 4]
In Example 3, instead of 100% by mass of the propylene polymer 1, a crystal nucleating agent (High Cycle Master RM An eye drop nozzle was produced in the same manner as in Example 3, except that M301 [manufactured by Dainichiseika Kogyo Co., Ltd.] was used and the mixture was injection molded.

[Example 5]
In Example 3, instead of 100% by mass of the propylene polymer 1, a crystal nucleating agent (High Cycle Master RM M301) was used, and an eye drop nozzle was produced in the same manner as in Example 3, except that the mixture was injection molded.

[Example 6]
In Example 3, instead of 100% by mass of the propylene polymer 1, a crystal nucleating agent (High Cycle Master RM M301) was used, and an eye drop nozzle was produced in the same manner as in Example 3, except that the mixture was injection molded.

<Density>
A 2-g test piece was cut from the eyedropper nozzle prepared in Examples 3 to 6, placed in a round-bottomed flask containing 100 mL of pure water, and heated under reflux for 2 hours. After that, the test piece cooled to room temperature was dried at 80° C. for 2 hours, and the mass Wa (g) of the obtained test piece was measured.
Next, the test piece was immersed in water having a density of 0.998 g/cm ³ and the mass Ws (g) of the test piece immersed in the water was measured.
The eyedrop nozzle density D (g/cm ³ ) was calculated from the following formula (4).
Eye drop nozzle density D=Wa×0.998/(Wa−Ws) (4)

<N-hexane non-volatile matter amount>
A 5.0 g test piece was cut from the eyedropper nozzles prepared in Examples 5 and 6, placed in a round-bottomed flask containing 50 mL of n-hexane, and heated to reflux for 4 hours. After that, the liquid obtained by cooling to room temperature is filtered to obtain a filtrate, and the obtained filtrate is placed in an evaporating dish, dried in a water bath, and dried at 105 ° C. for 2 hours. Body mass x3 (mg) was measured.
A blank test was performed in the same manner as described above, except that the test piece was not used, and the mass x4 (mg) of the resulting dried body was measured.
Using the measured masses x3 and x4, the amount of n-hexane non-volatile matter was calculated from the following formula (5). Table 2 shows the results. The results in Table 2 are the average values of the n-hexane non-volatile matter amounts measured and calculated by conducting tests using 5 specimens of the eye drop nozzles produced in each example.
Amount of n-hexane non-volatile matter (mg) = x3-x4 (5)

1: Container main body 2: Eye drop nozzle 3: Eye drop nozzle 11: Opening cylinder part 12: Bottom part 13: Body part 14: Shoulder part 21: Circular plate part 22: Outer cylinder part 23: Inner cylinder part 24: Liquid injection part 25: Liquid injection port 26: liquid passage part 31: liquid passage part 32: liquid injection part 33: collar part 34: outer wall 221: cap 222: convex part 311: inlet part 312: liquid injection port Y: ophthalmic solution (medicine)

Claims

An eyedropper member including at least one selected from an eyedropper container body and an eyedropper nozzle,
The eye drop container main body has a bottom portion, a hollow cylindrical body portion continuing to the periphery of the bottom portion, a shoulder portion continuing to the body portion, and an open cylindrical portion continuing to the shoulder portion,
An eyedropper, wherein the eyedropper container body and the eyedropper nozzle contain a propylene-based polymer and satisfy the following formula (1):
x1−x2≦60.0 mg (1)
For x1, cut a 5.0 g test piece from the body of the eyedropper body or from the eyedropper nozzle, cut the test piece to a size of 3 cm × 0.3 cm, and then fill 50 mL of n-hexane with a round bottom. Place in a flask, heat under reflux for 4 hours, cool to room temperature, filter the obtained liquid to obtain a filtrate, put the obtained filtrate in an evaporating dish, dry in a water bath, and then heat at 105 ° C. The mass (mg) of the dried body obtained by drying for 2 hours, and x2 is the dried body obtained by performing a blank test in the same manner as described above, except that the test piece was not used. Mass (mg).
The eyedropping member according to claim 1, wherein the propylene-based polymer contains 2.5% by mass or less of a component having a molecular weight of 10000 or less as measured by gel permeation chromatography.
The eyedropping member according to claim 1 or 2, wherein the propylene-based polymer is a copolymer of propylene and a monomer other than propylene, and the monomer other than propylene contains ethylene.
The eyedropping member according to claim 3, wherein the content of ethylene-derived structural units in the propylene-based polymer is 4.0% by mass or less with respect to 100% by mass of all structural units constituting the propylene-based polymer.
The eyedropper according to claim 1 or 2, wherein the propylene-based polymer has a melt flow rate of 0.1 to 30.0 g/10 minutes measured at 230°C under a load of 2.16 kg.
The eyedropping member according to claim 1 or 2, wherein the eyedropping member contains the propylene-based polymer and a crystal nucleating agent.
The eyedropping member according to claim 6, wherein the eyedropping member is an eyedropping nozzle.
7. The eye drop according to claim 6, wherein the eye drop has a density of 0.900-0.915 g/ cm3 .