JP6950312B2 - Liquid pharmaceutical compositions and pharmaceuticals - Google Patents

Description

The present invention relates to a liquid pharmaceutical composition and a pharmaceutical product that can be felt to stay in the mucous membrane.

In order to deal with inflammation of the esophagus and gastric mucosa, a porous water-insoluble inorganic particle component such as an antacid is generally blended. These have the effect of neutralizing gastric acid by themselves, and by staying on the mucous membrane of the stomach and esophagus, they are expected to have the effect of directly neutralizing on the spot and protecting the mucosa itself. Further, in order to deal with inflammation of the esophagus and gastric mucosa, a formulation technique for thickening a preparation with a polymer compound or the like to improve mucosal retention is disclosed.

On the other hand, mucosal irritants such as menthol and eugenol are absorbed through the mucous membranes of the esophagus and stomach immediately after taking the drug, thus giving a feeling of effect on the mucous membranes (eliminating discomfort in the esophagus and stomach) and a good feeling of taking. be able to. From the above, the composition is composed by using porous water-insoluble inorganic particles in combination with mucosal stimulating components such as menthol and eugenol to retain the mucosa and to feel irritation by the mucosal stimulant in the mucosa, especially in the esophagus. There has been a demand for a technique that allows the mucous membrane to stay in the mucosa.

JP-A-2002-193827

Although mucosal irritating components such as menthol and eugenol have the above effects, since these components are hydrophobic and low molecular weight, they are co-blended with a porous water-insoluble inorganic particle component and a liquid pharmaceutical composition containing water. In this case, we newly found the problem that the mucosal stimulating component is trapped in the porous material. As a result, even if the composition itself containing the mucosal irritant is retained in the mucous membrane, the irritation caused by the mucosal irritant cannot be felt, and there arises a problem that the composition cannot be actually retained. From this, in the present invention, the composition is retained in the mucous membrane, and by feeling the irritation of the mucosa, especially the esophagus, by the mucosal irritant, the composition can be felt to be retained in the mucosa, and the discomfort of the esophagus and stomach is eliminated. , An object of the present invention is to provide a liquid pharmaceutical composition and a pharmaceutical product having high uniformity of composition and easy to take.

As a result of diligent studies to achieve the above object, the present inventor (A) a water-soluble polymer compound, (B) a porous water-insoluble inorganic particle component, (C) a mucosal stimulating component, and (D) water. It was found that the composition can be retained in the mucosa by combining the above, and the composition can be felt to be retained in the mucosa by feeling the irritation caused by the mucosal stimulant in the esophagus when taken. It has been found that a liquid pharmaceutical composition that is easy to take can be obtained from the viewpoints of a feeling of throatiness, a feeling of residual mouth during administration, a feeling of residual mouth after swallowing, etc., and this has led to the present invention.

Therefore, the present invention provides the following invention.
[1]. A liquid pharmaceutical composition containing (A) a water-soluble polymer compound, (B) a porous water-insoluble inorganic particle component, (C) a mucosal irritating component, and (D) water.
[2]. The liquid pharmaceutical composition according to [1], wherein the component (C) is one or more selected from menthol, menthone, carvacrol, eugenol, capsaicin, vitamin E, hesperidin and osthol.
[3]. (C) The liquid pharmaceutical composition according to [2], wherein the component is selected from menthol, menthone, carvacrol, eugenol and capsaicin.
[4]. The liquid according to any one of [1] to [3], wherein the component (A) has a functional group selected from a linear alkyl group, a cyclic hydrocarbon chain, a carboxyl group, a hydroxyl group, an amino group and a hydroxyl group. Pharmaceutical composition.
[5]. The mass ratio of the component (A) represented by (A) / (B) to the component (B) is 0.01 to 0.4, and the component (A) represented by (A) / (C). The liquid pharmaceutical composition according to any one of [1] to [4], wherein the mass ratio of and the component (C) is 1.0 to 100.
[6]. The liquid pharmaceutical composition according to any one of [1] to [5], which comprises an aggregate of the component (A) and the component (C).
[7]. (I) A step of mixing the (A) component, the (C) component, and a part of the (D) component (the (D) component of the (I) step) to obtain a solution (I).
A step of mixing the components (II) and (B) with a part of the component (D) (component (D) of step (II)) to obtain a dispersion liquid (II), and (III) the above solution (I). The liquid pharmaceutical composition according to any one of [1] to [6], which is obtained by the step of mixing the dispersion liquid (II) with the dispersion liquid (II).
[8]. (I) A step of mixing the (A) component, the (C) component, and a part of the (D) component (the (D) component of the (I) step) to obtain a solution (I).
A step of mixing the components (II) and (B) with a part of the component (D) (component (D) of step (II)) to obtain a dispersion liquid (II), and (III) the above solution (I). ) And the dispersion liquid (II), the method for producing the liquid pharmaceutical composition according to any one of [1] to [6].
[9]. A pharmaceutical product in which the liquid pharmaceutical composition according to any one of [1] to [7] is filled in a resin container made of polyethylene, polypropylene or polyethylene terephthalate, or a container made of a glass bottle.

According to the present invention, by feeling the irritation of the mucosal irritant in the esophagus when taking the drug, the composition can be felt to stay (hereinafter, the feeling of staying may be described), and the discomfort of the esophagus and stomach is eliminated. It is possible to provide a liquid pharmaceutical composition having high uniformity of composition and easy to take.

Hereinafter, the present invention will be described in detail.
[(A) component]
The water-soluble polymer compound means a polymer compound in which 1 g is dissolved in 100 mL of water at 20 ° C. In the liquid pharmaceutical composition of the present invention (hereinafter, may be referred to as a composition), the component (A) is partially or completely dissolved, and it is more preferable that the component (A) is completely dissolved. By blending the component (A), the composition is thickened and the mucosal retention is improved, so that the medicinal effect of the blended drug is improved. Furthermore, when used in combination with the component (C) described later, the mucosal stimulating component is suppressed from being trapped in the porous medium, so that a feeling of retention can be obtained.

Examples of the water-soluble polymer compound include alginic acid derivatives such as xanthan gum, carrageenan, pectin, alginic acid and alginate, and propylene glycol alginate, gum-based polymer compounds such as guagam, gellan gum, and tamarind gum, hydroxypropyl starch, carboxymethyl cellulose, and hydroxy. Examples thereof include water-soluble polysaccharides such as alkyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone and agar, and water-soluble proteins such as gelatin and casein, and one type alone or two or more types can be used as appropriate. All of these are water-soluble and have a hydrocarbon chain or a functional group having an intramolecular interaction in the molecule. The intramolecular interaction refers to a hydrophobic interaction, an electrostatic interaction, a hydrogen bond, a dipole interaction, an ionic bond, and the like. Suitable hydrocarbon chains include linear alkyl groups such as ethyl groups and propyl groups, and cyclic hydrocarbon chains such as 5-membered rings. Examples of the interacting functional group include a 1-4, 1-6 glucosidic bond, a carboxyl group, a hydroxyl group, an amino group, a hydroxyl group, a hydroxypropyl group and the like. Among them, those having a functional group selected from a linear alkyl group such as an ethyl group and a propyl group, a cyclic hydrocarbon chain, a carboxyl group, a hydroxyl group, an amino group and a hydroxyl group are preferable.

The blending amount of the component (A) in the composition is preferably 0.08 to 3.0% by mass (hereinafter referred to as%), more preferably 0.1 to 2.0%, and 0.4 to 0.8. % Is more preferable. By setting it to 0.08% or more, it is possible to suppress trapping in the porosity of the mucosal stimulating component, and it is possible to obtain more retention in the esophageal / gastric mucosa. , The composition has an appropriate viscosity and is easy to take.

[(B) component]
Porous water-insoluble inorganic particle components include alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide, carbonates such as calcium carbonate and magnesium carbonate, synthetic hydrotalcites, magnesium aluminometasilicate, and the like. Acidic agents such as magnesium silicate aluminate, magnesium oxide, aluminum hydroxide, and magnesium hydroxide alumina can be used, and one type alone or two or more types can be used in combination as appropriate. By staying in the mucous membrane, these components have an on-site gastric acid neutralizing effect and the like. In addition, water insoluble means that 1 g does not dissolve in 100 mL of water at 20 ° C. The amount of water supplied is preferably 0.5 to 5 g / mL. When the water supply amount is 0.5 g / mL or more, a highly uniform composition can be obtained, and when the water supply amount is 5 g / mL or less, the feeling of retention is further improved. The amount of water supplied is measured by the "weight of added water" when water is added to the powder until liquid-like fluidity is exhibited.

The blending amount of the component (B) in the composition is preferably 1 to 24%, more preferably 2 to 16%, still more preferably 8 to 12%. When it is 1% or more, the desired antioxidative effect or the like can be further obtained, and when it is 24% or less, the composition viscosity becomes appropriate and it becomes easy to take.

The mass ratio of the component (A) represented by (A) / (B) to the component (B) is preferably 0.01 to 0.4, more preferably 0.013 to 0.25, and 0.025 to 0.025. 0.1 is even more preferred. When it is 0.01 or more, the effect of the component (B) is exhibited more quickly, and when it is 0.4 or less, the actual feeling of retention is further improved.

[(C) component]
The mucosal stimulating component is not particularly limited as long as it stimulates the mucous membrane to give a feeling of retention, and one type alone or two or more types can be used as appropriate. Specifically, essential oils such as fragrances, cooling components such as menthol, menthol, allyl isocyanate, caffeine, and cinnamaldehyde, warming components such as carbachlor, eugenol, and thymol, capsaicin, gingerol, shogaol, sanshool, and alicin. Examples include heat-sensing and stimulating components such as, vitamin E such as tocophenol acetate, and blood flow promoting components such as hesperidin and osthol. Further, as a processing raw material containing these, extracts such as mint, eucalyptus, cinnamon, mustard oil, eucalyptus, oregano, thyme, bay leaf, pepper, ginger, Japanese pepper, mushrooms, onions, and chili peppers can be used. Further, a processing raw material containing these components can also be used. Examples of the processing raw material include dried cinnamon extract, bay leaf extract (eugenol and the like), thyme dried extract (carvacrol, thymol, etc.), chili extract (capsaicin), mint (menthol) and the like. These components activate TRP receptors on the esophageal and gastric mucosa and give a feeling of retention.

Among them, a refreshing component, a warming component, a heat / stimulating component, and a blood flow promoting component are preferable, and menthol, menthol, carbacrol, eugenol, capsaicin, vitamin E, hesperidin and osthol are more preferable, and menthol, menthol, carbacrol, Eugenol and capsaicin are more preferred.

The blending amount of the component (C) in the composition is preferably 0.004 to 0.24%, more preferably 0.01 to 0.24%, still more preferably 0.05 to 0.08%. When it is 0.004% or more, a feeling of retention can be obtained more, and when it is 0.24% or less, an appropriate stimulus can be obtained.

The mass ratio of the component (A) represented by (A) / (C) to the component (C) is preferably 1.0 to 100, more preferably 1.25 to 40, and even more preferably 1.5 to 10. .. By setting the value to 1.0 to 100, a feeling of staying can be further obtained.

Although the mechanism of the effect of obtaining the feeling of retention of the present invention is unknown, functional groups having an intramolecular interaction of the component (A), particularly hydrophobic interaction and electrostatic interaction, work in combination, and (C) Due to the intramolecular interaction with the mucosal stimulating component, the (A) component and the (C) component form an aggregate, and the (C) mucosal stimulating component (B) in the particles of the porous water-insoluble inorganic particle component. It is expected that the feeling of staying will be improved by preventing trapping in. The aggregate can be confirmed by means such as NMR and IR.

[(D) component]
Purified water or the like can be used as the water, and the water is not particularly limited. The blending amount of the component (D) in the composition is preferably 70 to 99%, more preferably 75 to 98%.

Any component can be appropriately blended in the composition of the present invention as long as the effects of the present invention are not impaired. Examples of the optional component include other active ingredients, polyols, polymer compounds other than the above component (A), sweeteners, flavors, preservatives, flavoring agents, pigments, surfactants, oils, soluble inorganic components and the like. Be done.

Other active ingredients include ranitidine or ranitidine hydrochloride, famotidine, cimetidine, loxatidine hydrochloride acetate, nizatidine, laftidine, lansoprazole, labeprazole, omeprazole and other gastric acid secretion inhibitors, pyrenzepine, atropine, scopolamine and other muscarinic receptors. In addition to protective factor promoters such as antagonists, scralfert, aldioxa, azulene, L-glutamine, and levamipid, turmeric, kanzo, carrot, aulen, chowji, gentiana, sojutsu, ginseng, ginger, keihi, goshuyu, takusha, bukuryo, keihi , Chorei, Byakujutsu, Oubaku, Ogon, Sanshishi, Kijitsu, Chimpi, Koboku, Keihi, Uikyo, Mokko, etc. It may be blended.

As the polyol, sugar alcohols such as mannitol, erythritol, xylitol, sorbitol, palatinit and lactitol, monosaccharides, oligosaccharides and polysaccharides, as well as polyethylene glucol (PEG) and polyhydric alcohols such as glycerin and propylene glycol can be blended. .. Further, a lower alcohol such as ethanol can also be blended. When the component (A) is dissolved in the component (D), the component (A) can be quickly dissolved by dispersing the component (A) in ethanol in advance and then adding it to the water (D).

As the polymer compound other than the above component (A), a linear polymer compound such as polyethylene glycol can also be used.

Examples of the sweetener include sucrose, fructose, aspartame, sucralose, thaumatin, acesulfame potassium, sorbitol, stevia, purified sucrose, saccharin, glycyrrhizin and the like.

Examples of the flavor include known essential oils such as limonene, orange flavor, lychee flavor, lemon flavor, lime flavor, strawberry flavor, pineapple flavor, mint flavor, grapefruit flavor and the like. Examples of the pigment include caramel, carmine, carotene solution, β-carotene, copper chlorophyll, sodium copper chlorophyllin and the like.

Examples of the preservative include parabens such as alkylparaben, benzoic acid, paraoxybenzoic acid ester, sodium benzoate and the like.

[Production method]
The method for producing the liquid pharmaceutical composition of the present invention is not particularly limited, and examples thereof include a production method including the following steps.
(I) A step of mixing the (A) component, the (C) component, and a part of the (D) component (the (D) component of the (I) step) to obtain a solution (I).
A step of mixing the components (II) and (B) with a part of the component (D) (component (D) of step (II)) to obtain a dispersion liquid (II), and (III) the above solution (I). ) And the dispersion liquid (II)

The amount of the component (D) in the step (I) and the component (D) in the step (II) is not particularly limited, but further, a solvent such as ethanol is used in any step (particularly in the step (I)). be able to. The mass ratio ((I) (D) :( II) (D)) of the component (D) used in the step (I) to the component (D) used in the step (II) is 1: 0.3 to 1. : 10 is preferable. Further, in the step (I), the mass ratio of the component (D) is preferably 25 to 500 times that of the component (A), and in the step (II), the mass ratio of the component (D) is relative to the component (B). It is preferably 1 to 50 times.

In any process, it can be produced in a general-purpose liquid mixer at room temperature. In the above step (III), for example, when the solution (I) is added to the dispersion liquid (II), the dispersion liquid (II) is gradually added while being strongly stirred with a stirring blade or the like having a shearing ability. preferable.

[container]
Examples of the container for filling the oral liquid pharmaceutical composition of the present invention include a general bottle container, a resin container (both a bottle type and a single-use type can be used), and a glass bottle as a bottle container. .. As the resin material, general materials such as polyethylene, polypropylene, polyethylene terephthalate, and polyacrylonitrile can be used, and polyethylene, polypropylene, polyethylene terephthalate, and the like are preferable. A packaging container (pouch or the like) made of a laminate of a metal foil and a resin film can be used. As the resin material, the above-mentioned general material can be used, and in particular, polyethylene, polypropylene, polyethylene terephthalate or the like can be used as the innermost layer. As the metal foil, aluminum foil or the like can be used. Among them, since it is a liquid, an appropriate amount can be drunk at one time, and a resin pouch container is preferable from the viewpoint of portability and the like. The shape of the above-mentioned laminated packaging container can be freely formed such as a three-dimensional structure by pressure air or physical extrusion by a mold.

[Liquid pharmaceutical composition]
The liquid pharmaceutical composition of the present invention preferably has a viscosity (25 ° C.) of 0.1 to 5 Pa · s, more preferably 0.2 to 3 Pa · s. By setting this viscosity range, the amount of retention in the esophagus can be improved and it becomes easier to take. The viscosity was measured with a B-type viscometer (for example, DV2T type manufactured by Brookfield), 60 rpm, 25 ° C., and the rotor was appropriately selected according to the viscosity) (average value obtained by three measurements). The pH of the composition of the present invention is preferably 5-9.

The liquid pharmaceutical composition of the present invention is used orally and includes an aqueous solution, a suspension, an emulsion and the like. As the dosage form, all dosage forms corresponding to the section of the general formulation / oral solution of the Japanese Pharmacopoeia can be used. These can also be used for hard capsules, soft capsules, jellies, and liquid-encapsulated gummies. In that case, a shaping agent, a binder, a disintegrant, etc. of each dosage form can be blended. Of these, suspensions and emulsions are preferable.

Hereinafter, the present invention will be specifically described with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples. In the following examples, unless otherwise specified, "%" in the composition indicates mass%, the ratio indicates mass ratio, and the amount of each component in the table is the amount converted to pure content.

[Examples, comparative examples]
The compositions listed in the table below were prepared by the following methods.
[Example 1]
(I) 20 g of the component (A) and 4 g of the component (C) were dissolved in 666 g of water (I) (D) (three-one motor, 500 to 1,000 rpm, room temperature) to obtain a solution (I).
400 g of (II) and (B) were dispersed in 2,000 g of water (II) and (D) (three-one motor, 200 to 500 rpm, room temperature) to obtain a dispersion liquid (II).
(III) The solution (I) was gradually added and dissolved while stirring the dispersion liquid (II), and 1,910 g of the remaining water (D) was further added and stirred to obtain a composition.
Other Examples and Comparative Examples were prepared according to Example 1, and the obtained compositions were evaluated as follows. The results are shown in the table. The compositions of Examples were all liquid, and the pH was in the range of 5-9. Further, a 5 mL aluminum laminate packaging container (manufactured by Fujimori Kogyo Co., Ltd., aluminum laminate film (polyethylene, aluminum, PET, polyethylene from the innermost layer)) was filled with 5 mL of the obtained composition to obtain a pharmaceutical product. The composition of 5,000 mg (about 5 mL) is shown in the table.

[Viscosity measurement]
The composition was placed in a 200 mL glass bottle and measured using a B-type viscometer (Brookfield, DV2T type, 60 rpm, 25 ° C., rotor appropriately selected according to viscosity).

[Homogeneity]
About 10 mL of the composition was filled into a 15 mL centrifuge tube. Based on the following evaluation criteria, the properties and appearance after standing for 1 day were confirmed.
[Evaluation criteria]
4: Uniformly dispersed, no supernatant 3: There is a slight amount of supernatant, but less than 10% by volume of the whole, and evenly dispersed by shaking 2: The supernatant is 10% by volume or more of the whole, but uniform by shaking Disperse in 1: There is a supernatant or a precipitate, and 2 points or more that do not disperse uniformly even when shaken are accepted.

[Easy to take / feeling of staying]
Four panelists (healthy adult men and women) took 5 mL of the composition filled in a 5 mL aluminum-laminated packaging container, and the ease of taking and the feeling of retention after 3 minutes were evaluated on a 5-point scale. The results are shown as an average of 4 people.

[Ease of administration evaluation criteria: Comprehensive evaluation of throat feeling, residual feeling in the mouth when taking, and residual feeling in the mouth after swallowing]
5: Very easy to take: There is a clear throat feeling and no residual feeling in the mouth 4: Easy to take: There is no clear throat feeling, but it does not stick to the mouth and there is no residual feeling 3 : Neither: No clear throat feeling, sticking to the mouth, but no residual feeling after swallowing 2: Difficult to take: Sticking to the mouth, slight residual feeling after swallowing Yes 1: Very difficult to take: The average value of 4 panelists who remained clearly in the mouth and had a feeling of residual after swallowing was 3.0 points or higher.

[Feeling of staying: Evaluating mucosal irritation felt in the esophagus as feeling of staying]
5: Very strong 4: Strong feeling 3: Slightly felt 2: Slightly felt 1: Little or no feeling The average value of the four panelists was 3.0 points or higher.
In addition, the following feelings of staying were explained to the panelists in advance.
Menthol: refreshing, carvacrol, eugenol: warmth

The raw materials used in the above example are shown below. Unless otherwise specified, the amount of each component in the table is a net conversion amount.
Hydroxypropyl cellulose: "HPC-L" manufactured by Nippon Soda Co., Ltd.
Carrageenan: "GENUVISCO JJ" manufactured by Sansho Co., Ltd.
Sodium alginate: "Kimika Algin" manufactured by Kimika Co., Ltd.
Polyvinyl alcohol: "Polyvinyl alcohol (Wako first grade)" manufactured by Wako Pure Chemical Industries, Ltd.
Carboxymethyl cellulose: "CMC Daicel 1160" manufactured by Daicel Chemical Industries, Ltd.
Xanthan gum: "Echo gum" manufactured by DSP Gokyo Food & Chemical Co., Ltd.
Hydroxypropyl starch: "HPS101" manufactured by Freund Sangyo Co., Ltd.
Agar: "Agar (special grade reagent)" manufactured by Wako Pure Chemical Industries, Ltd.
Gelatin: "Gelatin AP-270" manufactured by Nitta Gelatin Co., Ltd.
Magnesium aluminate metasilicate: "Neucillin NFL2N" manufactured by Fuji Chemical Industry Co., Ltd.
Magnesium aluminate silicate: "Neucillin A (AS)" manufactured by Fuji Chemical Industry Co., Ltd.
Magnesium carbonate: "Basic magnesium carbonate (heavy)" manufactured by Wako Pure Chemical Industries, Ltd.
Magnesium oxide: "Magnesium oxide (special grade reagent)" manufactured by Wako Pure Chemical Industries, Ltd.
Aluminum hydroxide: "Dry aluminum hydroxide gel SN" manufactured by Kyowa Chemical Industry Co., Ltd.
Synthetic hydrotalcite: "Alcamac VF" manufactured by Kyowa Chemical Industry Co., Ltd.
Menthol: "Super Menthol 3003" manufactured by Nagaoka Kogyo Co., Ltd.
Carvacrol: "Carvacrol" manufactured by Wako Pure Chemical Industries, Ltd.
Eugenol: "Eugenol" manufactured by Tokyo Chemical Industry Co., Ltd.
5mL aluminum laminated packaging container: Made by Fujimori Kogyo Co., Ltd., aluminum laminated film (polyethylene, aluminum, PET, polyethylene from the innermost layer) sealed on all four sides

Claims (9)

One or two selected from (A) water-soluble polymer compound, (B) porous water-insoluble inorganic particle component, (C) menthol, menthone, carvacrol, eugenol, capsaicin, vitamin E, hesperidin and osthol. The above , and (D) a liquid pharmaceutical composition containing water. The liquid pharmaceutical composition according to claim 1, wherein the content of the component (C) is 0.01 to 0.08% by mass in the composition. The liquid pharmaceutical composition according to claim 1 or 2, wherein the component (C) is selected from menthol, menthone, carvacrol, eugenol and capsaicin. The liquid pharmaceutical according to any one of claims 1 to 3, wherein the component (A) has a functional group selected from a linear alkyl group, a cyclic hydrocarbon chain, a carboxyl group, a hydroxyl group, an amino group and a hydroxyl group. Composition. The mass ratio of the component (A) represented by (A) / (B) to the component (B) is 0.01 to 0.4, and the component (A) represented by (A) / (C). The liquid pharmaceutical composition according to any one of claims 1 to 4, wherein the mass ratio of and the component (C) is 1.0 to 100. The liquid pharmaceutical composition according to any one of claims 1 to 5, wherein the mass ratio of the component (A) represented by (A) / (C) to the component (C) is 1.5 to 25.0. .. The liquid pharmaceutical composition according to any one of claims 1 to 6 , which comprises an aggregate of the component (A) and the component (C). (I) A step of mixing the (A) component, the (C) component, and a part of the (D) component (the (D) component of the (I) step) to obtain a solution (I).
A step of mixing the components (II) and (B) with a part of the component (D) (component (D) of step (II)) to obtain a dispersion liquid (II), and (III) the above solution (I). ) And the dispersion liquid (II), the method for producing the liquid pharmaceutical composition according to any one of claims 1 to 7. A pharmaceutical product in which the liquid pharmaceutical composition according to any one of claims 1 to 7 is filled in a resin container made of polyethylene, polypropylene or polyethylene terephthalate, or a container made of a glass bottle.