JP2019019061A - Oral liquid pharmaceutical composition and pharmaceutical - Google Patents

Abstract

To provide an oral liquid pharmaceutical composition that is easy to swallow, and suppresses a discomfort taste or flavor just after ingestion and even after a lapse of long time, offering good (easy) ingestibility, and contains an unpleasant taste crude drug extraction component, and provide a pharmaceutical.SOLUTION: An oral liquid pharmaceutical composition contains (A) an unpleasant taste crude drug extraction component, (B) a water-soluble polymer compound, (C) a sweetener, (D) a flavor and (E) water.SELECTED DRAWING: None

Description

  The present invention relates to an oral liquid pharmaceutical composition and a medicine containing an unpleasant taste crude drug extract component.

  Herbal medicine, which is a healthy stomach component, is blended as an active ingredient of oral medicine such as gastrointestinal drugs. However, many crude drugs have an unpleasant taste and aroma. In particular, internal liquids and orally disintegrating tablets directly feel the unpleasant taste derived from herbal medicines, so the problem is that the ingestion becomes worse by blending herbal medicines.

  A fragrance | flavor etc. may be added in order to mask the unpleasant taste and fragrance of a crude drug. However, although this method can mask the initial taste, it has been a challenge to feel an unpleasant taste over time. In view of the above, there has been a demand for a technique that can reduce the unpleasant taste immediately after taking and after the time after taking.

JP 2008-094742 A

  The present invention has been made in view of the above circumstances, is easy to swallow, and has an unpleasant taste and aroma that is suppressed immediately after taking and after taking time, so that it is easy to take (easy to take), unpleasant taste An object of the present invention is to provide an oral liquid pharmaceutical composition and a pharmaceutical product containing herbal extract components.

  As a result of intensive studies to achieve the above object, the present inventor has (B) a water-soluble polymer compound, (C) a sweetener, and (A) an oral liquid pharmaceutical composition containing an unpleasant tasting crude drug extract component. D) It has been found that the above problems can be solved by using a fragrance in combination, and the present invention has been made.

Accordingly, the present invention provides the following inventions.
[1]. An oral liquid pharmaceutical composition comprising (A) an unpleasant taste crude drug extract component, (B) a water-soluble polymer compound, (C) a sweetener, (D) a fragrance, and (E) water.
[2]. The blending amount of the components (A) to (D) in the oral liquid pharmaceutical composition is (A) component 1 to 20% by mass, (B) component 0.04 to 2.0% by mass, (C) component 0. 002-0.2% by mass, (D) component 0.002-0.12% by mass, and the mass ratio of (A) / (B) component represented by (A) / (B) is 2 To 100, the mass ratio of the component (A) represented by (A) / (C) to the component (C) is 10 to 2,000, and the component (A) represented by (A) / (D) (D) The oral liquid pharmaceutical composition of [1] whose mass ratio with a component is 10-2,000.
[3]. The blending amounts of the components (A) to (D) in the oral liquid pharmaceutical composition are (A) component 1 to 10% by mass, (B) component 0.1 to 1.0% by mass, (C) component 0. 01 to 0.2% by mass, (D) component 0.01 to 0.12% by mass, and the mass ratio of (A) / (B) component represented by (A) / (B) is 2 The mass ratio of the (A) component represented by (A) / (C) and the (C) component is 10 to 400, and the (A) component represented by (A) / (D) (D) The oral liquid pharmaceutical composition of [2] description whose mass ratio with a component is 10-400.
[4]. (B) The liquid pharmaceutical composition according to any one of [1] to [3], wherein the component has a functional group selected from a carboxyl group, a hydroxyl group, an amino group, an amide group, and a sulfate group.
[5]. [1] to [4] A pharmaceutical product in which the liquid pharmaceutical composition according to any one of [1] to [4] 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, it is possible to provide an oral liquid pharmaceutical composition containing an unpleasant-tasting herbal medicine extract component that is easy to swallow, has an unpleasant taste and aroma that is suppressed immediately after taking and after the time has elapsed, and has good takeability. Can do.

Hereinafter, the present invention will be described in detail. Hereinafter, the oral liquid pharmaceutical composition may be referred to as “composition”.
[(A) component]
As an unpleasant taste crude drug extraction component, if it mix | blends with a pharmaceutical composition, it will not specifically limit, 1 type can be used individually or in combination of 2 or more types. For example, turmeric, licorice, carrot, auren, clove, gentian, gentian, keihi, ginger, goshyu, takusha, bukuryo (茯苓), keihi (cinnamon), chorei (猪苓), biakujutsu (white moth), oak (yellow candy), Herbal medicine extract components such as urgon, sanshishi (yamashiko), pheasant, chimpi, kokuboku, fennel, clove, mokko, hange, and lysam can be used. The extraction method is not particularly limited, and can be used not only as a raw powder but also as a raw material for processing such as a stream extract, a dry extract, and a tincture.

  (A) As for the compounding quantity in the composition of a component, 1-20 mass% (it is hereafter set as%) is preferable, 1-10% is more preferable, and 4-8% is more preferable. By setting it to 1% or more, a medicinal effect due to sufficient herbal medicine blending is obtained, and by setting it to 20% or less, unpleasant taste and aroma are further suppressed, and the ingestion is further improved.

[Component (B)]
By blending the component (B), a remarkable unpleasant taste / scent suppressing effect that cannot be obtained by simply blending the sweetener (C) and the flavor (D) is obtained. The water-soluble polymer compound refers to a polymer compound in which 1 g is dissolved in 100 mL of water at 20 ° C. In the composition of the present invention, the component (B) is partially or completely dissolved in the oral liquid pharmaceutical composition. Uncomfortable taste and fragrance derived from the highly volatile essential oil component of component (A) (discomfort after time has elapsed after taking) by being partly or completely dissolved in the oral liquid pharmaceutical composition Nasty taste and fragrance). From the viewpoint of such action and effects, it is more preferable that the component (B) is completely dissolved in the oral liquid pharmaceutical composition.

  Examples of water-soluble polymer compounds include xanthan gum, carrageenan, pectin, chondroitin and its sulfates, alginic acid derivatives such as alginic acid and alginic acid salts, propylene glycol alginate, gum based polymer compounds such as guar gum, gellan gum, tamarind gum, carboxymethyl cellulose , Hydroxypropyl starch, hydroxyalkyl cellulose, polyvinyl pyrrolidone, polyvinyl alcohol, water-soluble polysaccharides such as agar, water-soluble proteins such as gelatin and casein, and the like, which may be used alone or in appropriate combination of two or more. Can do. These are all water-soluble and have a hydrocarbon chain in the molecule.

  Among them, a polymer compound having a hydrophilic functional group such as a carboxyl group, a hydroxyl group, an amino group, an amide group, or a sulfate group is preferable, and those that form a higher order structure when an aqueous solution is used are preferable. Unlike higher-order structures such as vinyl polymers such as polyvinyl alcohol and linear polymer compounds such as polyoxyethylene polymers such as polyethylene glycol, a higher-order structure forms a three-dimensional network structure by branching many molecular chains. To do. Examples of such water-soluble polymer compounds include xanthan gum, hydroxypropylcellulose, carrageenan, pectin, alginic acid and alginates, alginic acid derivatives, carboxymethylcellulose and the like. They interact with metal ions (such as alkaline earth metals) to form higher order gel networks and can effectively confine unpleasant taste components. As what has such a metal ion, the (F) component mentioned later can be mentioned.

  The blending amount of the component (B) in the composition is preferably 0.04 to 2.0%, more preferably 0.1 to 1.0%, and still more preferably 0.4 to 0.6%. By setting it to 0.04% or more, unpleasant taste and aroma are further suppressed, and by setting it to 2.0% or less, the viscosity is not too high and it is easier to take.

[Component (C)]
The sweetener is not particularly limited. , Neotome, aritem and the like. These can be used individually by 1 type or in combination of 2 or more types. Of these, sucralose and aspartame are preferable.

  The amount of component (C) in the composition is preferably 0.002 to 0.2%, more preferably 0.01 to 0.2%, and still more preferably 0.04 to 0.12%. By setting it to 0.002% or more, unpleasant taste and aroma, especially 0.2% or less after elapse of time after taking, it is easier to take with moderate sweetness.

[(D) component]
Although it does not specifically limit as a fragrance | flavor, since the unpleasant taste and fragrance of (A) component are suppressed effectively, citrus-type fragrance | flavors, such as grapefruit flavor, orange flavor, lemon flavor, lime flavor, sudachi flavor, and sea quasar flavor. Preferably, the essential oil itself is used as the fragrance.

  (D) As for the compounding quantity in the composition of a component, 0.002-0.12% is preferable, 0.01-0.12% is more preferable, 0.04-0.08% is further more preferable. By making it 0.002% or more, unpleasant taste and scent, particularly unpleasant taste and scent just before taking, are further suppressed, and by making it 0.12% or less, it is easier to take with moderate scent.

  2-100 are preferable, as for mass ratio of (A) component represented by (A) / (B), and (B) component, 2.5-100 are more preferable, and 6.67-20 are more preferable. By setting it to 2 or more, a medicinal effect by sufficient herbal medicine blending is obtained, and by setting it to 100 or less, unpleasant taste and aroma are further suppressed.

  10-2,000 are preferable, as for mass ratio of (A) component represented by (A) / (C), and (C) component, 10-400 are more preferable, and 33.3-100 are more preferable. By setting it to 10 or more, it is easier to take with moderate sweetness, and by setting it to 2,000 or less, unpleasant taste and scent, especially unpleasant taste and scent after time has elapsed after taking, are further suppressed. Is done.

  10-2,000 are preferable, as for mass ratio of (A) component represented by (A) / (D), and (D) component, 10-400 are more preferable, and 50-100 are more preferable. By setting it to 10 or more, it is easier to take with a moderate scent, and by setting it to 2,000 or less, an unpleasant taste and scent, particularly an unpleasant taste and scent just before taking are further suppressed.

[(E) component]
The water is not particularly limited as purified water. (E) 70.0-99.0% of the compounding quantity in the composition of a component is preferable, and 75.0-98.0% is more preferable.

[(F) component]
It is preferable to mix | blend metal ions, such as an alkaline-earth metal, with the composition of this invention as a component which interacts with the said (B) component and forms a high order gel network. As metal ions, calcium, magnesium, zinc, aluminum, and the like, inorganic compounds containing these, antacids, and the like can be blended. As antacids, alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide, carbonates such as calcium carbonate and magnesium carbonate, synthetic hydrotalcite, magnesium aluminate metasilicate, magnesium aluminate silicate, Examples thereof include magnesium oxide, aluminum hydroxide, and magnesium hydroxide alumina.

  As for the compounding quantity in the composition of (F) component, it is preferable that mass ratio of the metal ion of (B) :( F) component is 100: 4-100: 25.

  In the composition of the present invention, optional components can be appropriately blended within a range not impairing the effects of the present invention. Examples of optional components include other active ingredients, polyols (excluding the above component (C)), tasting ingredients such as menthol, preservatives, dyes, surfactants, oils, and bases.

  Other active ingredients include ranitidine or ranitidine hydrochloride, famotidine, cimetidine, roxatidine acetate hydrochloride, nizatidine, lafutidine, lansoprazole, rabeprazole, omeprazole and other muscarinic receptors such as pirenzepine, atropine, scopolamine You may mix | blend defense factor promoters, such as an antagonist, sucralfate, aldioxa, azulene, L-glutamine, rebamipide, and teprenone.

  Polyols can be blended with polyethylene glycol (PEG) and polyhydric alcohols such as glycerin and propylene glycol. Moreover, lower alcohols, such as ethanol, can also be mix | blended.

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

[Production method]
Although the manufacturing method of the composition of this invention is not specifically limited, It can manufacture in the procedure of mix | blending a normal liquid pharmaceutical formulation. (A) Raw material extraction components may be used as they are, or processed raw materials such as extracts may be used. In that case, the blending amount is determined from the amount of the bulk drug equivalent. (B) The polymer compound may be dissolved in water as it is, or may be dissolved after being previously dispersed in ethanol, propylene glycol or the like.

[Oral liquid pharmaceutical composition]
The viscosity of the liquid pharmaceutical composition of the present invention is preferably 0.1 to 5 Pa · s, and more preferably 0.2 to 3 Pa · s. By setting it as this viscosity range, the amount of staying in the esophagus can be improved and more easily taken. The viscosity was measured with a B-type viscometer (for example, Brookfield, DV2T type), 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 oral liquid pharmaceutical composition of the present invention includes aqueous solutions, suspensions, emulsions and the like. As the dosage form, all of the dosage forms corresponding to the items of the general rules of formulation and oral solution of the Japanese Pharmacopoeia can be used. They can also be used in hard capsules, soft capsules, jelly agents, and liquid-containing gummy. In that case, the excipient | filler of each dosage form, a binder, a disintegrating agent, etc. can be mix | blended. Of these, suspensions and emulsions are preferred.

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

  EXAMPLES Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example. In the following examples, unless otherwise specified, “%” in the composition indicates mass%, the ratio indicates the mass ratio, and the amount of each component in the table is an amount converted into a pure component.

[Examples and Comparative Examples]
The liquid composition described in the following table was prepared by mixing each component. (A) The quantity of a component shows an amount equivalent to an active ingredient.
The following evaluation was performed about the obtained composition. The results are shown in the table. In addition, all the compositions of the examples were liquid and the pH ranged from 5 to 9. Furthermore, 5 mL of an aluminum laminate packaging container (manufactured by Fujimori Kogyo Co., Ltd., aluminum laminate film (from the innermost layer to polyethylene, aluminum, PET, polyethylene)) was filled with 5 mL of the resulting composition to obtain a pharmaceutical product. In the table, the composition is 5,000 mg (about 5 mL).

[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 selected appropriately according to viscosity).

[Ingestion (ease of swallowing, unpleasant taste immediately after taking and after taking time (after 15 minutes), fragrance suppressing effect)]
Four panelists (healthy adult men and women) took 5 mL of the composition filled in a 5 mL aluminum laminate packaging container and evaluated it according to the following evaluation criteria.
<Evaluation criteria for ease of swallowing>
4: Very easy to swallow 3: Slightly easy to swallow 2: Slightly difficult to swallow 1: Very difficult to swallow

[Evaluation criteria for unpleasant taste and aroma suppression]
4: Almost / not at all 3: Slightly felt 2: Strongly felt 1: Very strongly felt The average value of four panelists at each time point was calculated. Regarding the unpleasant taste, the evaluation result immediately after taking and 15 minutes later was used as a criterion. A sample having an easiness of swallowing and an unpleasant taste of 2.5 or more was regarded as acceptable.

The raw materials used in the above examples are shown below. Unless otherwise specified, the amount of each component in the table is a pure conversion amount.
Kokuboku: “Kokuboku Style Extract” manufactured by Nippon Powder Chemical Co., Ltd.
Sojutsu: “Soryu Extract” manufactured by Nippon Powder Chemicals Co., Ltd.
Turmeric: Nippon Turbine Chemical Co., Ltd., “turmeric style extract”
Licorice: Nippon Kanko Pharmaceutical Co., Ltd., “licorice extract”
Ouren: "Ouren extract" manufactured by Nippon Powder Chemical Co., Ltd.
Owaku: Nippon Powdery Chemical Co., Ltd., “Owaku powder”
Chimpi: Nippon Chiyaku Pharmaceutical Co., Ltd., “Chimpi extract”
Xanthan Gum: DSP Gokyo Food & Chemical Co., “Echo Gum”
Alginic acid: “Kimika Argin” manufactured by Kimika Co., Ltd.
Propylene glycol ester alginate: manufactured by Kimika Co., Ltd. “Kimiloid”
Carboxymethylcellulose: “CMC Daicel 1160” manufactured by Daicel Chemical Industries, Ltd.
Polyvinyl alcohol: Wako Pure Chemical Industries, Ltd., “Polyvinyl alcohol (Wako first grade)”
Hydroxypropyl cellulose: Nippon Soda Co., Ltd., “HPC-L”
Hydroxypropyl starch: “HPS101” manufactured by Freund Sangyo Co., Ltd.
Sucralose: “Sucralose (P)”, manufactured by Saneigen FFI Co., Ltd.
Aspartame: “Puls Sweet Diet” manufactured by Ajinomoto Co., Inc.
Stevia: “Stevia Extract ST-AB”, manufactured by San-Ei Gen FFI Co., Ltd.
Saccharin sodium: Wako Pure Chemical Industries, Ltd., “Saccharin sodium (special grade reagent)”
Grapefruit flavor: Taiyo Fragrance Co., Ltd., “Grapefruit Fragrance”
Orange flavor: Taiyo Fragrance Co., Ltd., “Orange Fragrance”
Lemon flavor: Taiyo Fragrance Co., Ltd. “Lemon Flavor”
5mL aluminum laminate packaging container: made by Fujimori Kogyo Co., Ltd., sealed with aluminum laminate film (polyethylene, aluminum, PET, polyethylene)

Claims (5)

  An oral liquid pharmaceutical composition comprising (A) an unpleasant taste crude drug extract component, (B) a water-soluble polymer compound, (C) a sweetener, (D) a fragrance, and (E) water.   The blending amount of the components (A) to (D) in the oral liquid pharmaceutical composition is (A) component 1 to 20% by mass, (B) component 0.04 to 2.0% by mass, (C) component 0. 002-0.2% by mass, (D) component 0.002-0.12% by mass, and the mass ratio of (A) / (B) component represented by (A) / (B) is 2 To 100, the mass ratio of the component (A) represented by (A) / (C) to the component (C) is 10 to 2,000, and the component (A) represented by (A) / (D) The oral liquid pharmaceutical composition according to claim 1, wherein the mass ratio of the component (D) is 10 to 2,000.   The blending amounts of the components (A) to (D) in the oral liquid pharmaceutical composition are (A) component 1 to 10% by mass, (B) component 0.1 to 1.0% by mass, (C) component 0. 01 to 0.2% by mass, (D) component 0.01 to 0.12% by mass, and the mass ratio of (A) / (B) component represented by (A) / (B) is 2 The mass ratio of the (A) component represented by (A) / (C) and the (C) component is 10 to 400, and the (A) component represented by (A) / (D) The oral liquid pharmaceutical composition according to claim 2, wherein the mass ratio of component (D) is 10 to 400.   The liquid pharmaceutical composition according to any one of claims 1 to 3, wherein the component (B) has a functional group selected from a carboxyl group, a hydroxyl group, an amino group, an amide group and a sulfate group.   The pharmaceutical which filled the liquid pharmaceutical composition of any one of Claims 1-4 into the container made from a resin container comprised from polyethylene, a polypropylene, or a polyethylene terephthalate, or the container consisting of a glass bottle.