KR20110001900A - Composition for oral use - Google Patents

Abstract

PURPOSE: A composition for oral administration containing ibuprofen is provided to shield unpleasant taste without throat irritation. CONSTITUTION: A medicinal composition for oral administration contains 5-80 mass% of ibuprofen, 0.01-10 mass% of sucralose and 0.01-2 mass% of grape fruit flavoring agent. The mass ratio of sucralose and grape fruit flavoring agent is 1/0.01~1/1(=100~1). The mass ratio of ibuprofen and sucralose is 1/0.01~1/0.5(=100~2). The composition contains sugar alcohol. A granular agent, oral disintegrated tablet or troches contains the medicinal composition.

Description

Oral composition {COMPOSITION FOR ORAL USE}

The present invention relates to an oral preparation having good dose, in which the unpleasant taste (bitterness) of ibuprofen is suppressed and there is no throat irritation.

Many drugs have an unpleasant taste, and when an oral preparation containing them is used, studies have been made to mask the unpleasant taste derived from the drug. In particular, since tablets (oral disintegrating tablets, troches, etc.), granules, liquids, and jellys, which are taken without using water, are preparations that make the patient feel unpleasant, the masking is an important problem. do.

In order to solve the said subject, the masking technique which adds a sweetener and a fragrance | flavor is conventionally reported. However, sweeteners and fragrances were not necessarily satisfactory, such as not being able to mask a sufficiently unpleasant taste, a bitter taste derived from the fragrance, or a decrease in the dose due to the aftertaste of the sweetener.

Among the drugs, ibuprofen, besides bitter taste, has a throat irritation, such as stinging when swallowed, and a poor feeling of taking. In particular, solid preparations (tablets, granules) and jellys containing active ingredients at a higher concentration than liquids and the like have strong feelings of irritation of the throat, and therefore, a solution is desired.

Patent Document 1: Japanese Patent Application Laid-Open No. 2001-106639

An object of the present invention is to provide an oral composition having an unpleasant taste derived from ibuprofen and having good dose.

Another object of the present invention is to provide an oral composition having a good dose, in which throat stimulation derived from ibuprofen is reduced.

The inventors of the present invention have studied the above problems, and, in the case of containing ibuprofen, in addition to ibuprofen, by selecting scalose as a sweetener and grapefruit flavor as a flavor, it is excellent in bitterness masking effect and throat. It was confirmed that the irritation was reduced, and there was no aftertaste of the sweetener, and an oral preparation excellent in the dose was obtained, and the present invention was completed.

That is, the present invention,

<1> oral pharmaceutical composition containing ibuprofen, scalose and grapefruit flavoring agent;

<2> oral pharmaceutical composition as described in <1> characterized by being a scalose / grapefruit flavoring (mass ratio) = 1 / 0.01 to 1/1 (= 100 to 1);

The oral pharmaceutical composition as described in <1> characterized by the <3> ibuprofen / scalose (mass ratio) = 1 / 0.01-1 / 0.5 (= 100-2);

<4> <1>-<3 whose content of ibuprofen is 5-80 mass% in a formulation, content of scalose is 0.01-10 mass% in a formulation, and content of grapefruit fragrance is 0.01-2 mass% in a formulation. Oral pharmaceutical compositions described in>;

<5> Furthermore, the oral pharmaceutical composition as described in <1>-<4> containing sugar alcohol;

<6> Provided are granular agents, oral disintegrating tablets, or troches comprising the oral pharmaceutical composition according to <1> to <5>.

According to the constitution of the present invention, an oral pharmaceutical composition in which the unpleasant taste of ibuprofen and the throat irritation are sufficiently suppressed can be obtained, and in particular, tablets or granules to be taken without water such as chewable tablets, intraoral disintegrating tablets or troches. It is useful as a component of an agent.

(1) ibuprofen

Ibuprofen is a known nonsteroidal anti-inflammatory agent and is a drug that is formulated as an active ingredient of antipyretic analgesics and cold medicines. Ibuprofen used in the present invention can be used without particular limitation so long as it can be used for oral use, and may be in any form of powder or granulated material.

In terms of masking, the blended amount of ibuprofen is preferably 60 mass% or less in the oral composition, more preferably 50 mass% or less, particularly preferably 40 mass% or less. From the viewpoint of drug efficacy, a blending amount of 5% by mass or more, in particular 10% by mass or more is preferable, but in the use of ibuprofen not having the constitution of the present invention, the problem of throat irritation becomes more pronounced as the blending amount of ibuprofen increases.

(2) Scralose

The sweetener used in the oral pharmaceutical composition of the present invention requires scalose. Scralose is a well-known sweetener which can be mix | blended with oral medicine similarly to acesulfame potassium, aspartame, stevia, saccharin, etc., and can use a commercially available thing.

It is preferable to make content of the scalose used by this invention into 0.01-10 mass% in an oral composition, More preferably, it is 0.05-10 mass%, Especially preferably, it is 0.1-6 mass%. In 0.01 mass% or less, bitterness masking may not be enough, and when it exceeds 10 mass%, the bitter taste of a high sweetness sweetener may arise, or the aftertaste feeling of sweetness may become strong, and a dose may worsen.

Moreover, ibuprofen / scalose (mass ratio) = 1 / 0.01-1 / 0.5 are preferable, More preferably, it is 1 / 0.05-1 / 0.5. In the above range, it is particularly excellent in the effect of inhibiting throat stimulation of ibuprofen.

(3) grapefruit flavoring

The oral composition of this invention contains grapefruit fragrance as a fragrance | flavor. By using grapefruit flavoring, the effect of masking the bitter taste of a drug is high, and it can be set as the oral preparation which was excellent in a feeling of taking that the aftertaste of the sweetness of the said high sweetness sweetener was suppressed. The grapefruit flavoring agent is known as a citrus flavoring substance having the same fragrance as grapefruit containing d-limonene as the main ingredient (60 to 99.9% by mass), and includes nut carton as a bitter ingredient unique to grapefruit. The present invention effectively masks an unpleasant taste of a drug by using a combination of grapefruit flavor containing a lot of limonene and a high sweetness sweetener, and the bitterness component of the sweetness of the high sweetness sweetener (particularly scalose) Since the aftertaste is suppressed, the remarkable effect of the present invention can be obtained.

It is preferable that it is 20-99 mass% in grapefruit fragrance, and, as for content of d-limonene, it is more preferable that it is 40-97 mass%.

It is preferable that it is 0.0001-5.0 mass% in grapefruit fragrance, and, as for content of a nut carton, it is more preferable that it is 0.001-2.0 mass%.

It is preferable that the grapefruit flavoring agent which concerns on this invention contains the said d-limonene and a nut carton at the same time, respectively.

The grapefruit flavoring agent used in the present invention can be prescribed by appropriately adjusting the natural flavoring material and the synthetic flavoring material. As natural fragrance material, white grapefruit, red grapefruit, pink grapefruit, etc. are mentioned, Essential oil obtained by methods, such as conventional steam distillation or the crimping method, can be used suitably in the said technical field. have. As the synthetic perfume material, various volatile perfume components contained in grapefruit, such as naringin, alcohols, aldehydes, esters, ethers, ketones, in addition to the limonene and nut carton, can be appropriately used.

In addition, although the fragrance | flavor may mix | blend a liquid fragrance | flavor as it is or as the fragrance particle which carried on the carrying particle, Preferably, fragrance particle is used.

Examples of the supported particles include dextrin, gum arabic, starch, reduced palatinose, and the like, and gum arabic is preferable. Further, at least the d-limonene is 1 to 50% by mass, more preferably 2 to 40% by mass, more preferably 2 to 40% by mass of the gum arabic, and 0.000005 to 0.25% by mass of the arabic gum, more preferably, to the supported particles. It is preferable to set it as fragrance particle | grains, respectively, so that it may become 0.00005 to 0.1 mass%.

It is preferable to make content of the grapefruit fragrance used by this invention into 0.01-2 mass% in an oral composition, More preferably, it is 0.01-1 mass%. In 0.01 mass% or less, bitterness masking and the high sweetness sweetness suppression of the aftertaste suppression may not be enough, and in 2 mass% or more, the bitterness derived from grapefruit becomes strong, and there is a possibility that a dose may worsen.

Further, scalose / grapefruit flavoring (mass ratio) is preferably 1 / 0.001 to 1/10, more preferably 1 / 0.01 to 1/1 (= 100 to 1) (particularly preferably 1 / 0.1 to 1 / 0.5). In the above range, it is particularly excellent in the effect of inhibiting throat stimulation of ibuprofen.

The mass ratio (Ibuprofen / Scralose / Grapefruit Flavor) of ibuprofen, scalose and grapefruit flavoring used in the present invention is preferably 1 / 0.01 / 0.00001 to 1 / 0.5 / 5, more preferably. Is 1 / 0.05 / 0.0005 to 1 / 0.5 / 0.5, particularly preferably 1 / 0.05 / 0.005 to 1 / 0.5 / 0.25, most preferably 1 / 0.1 / 0.01 to 1 / 0.5 / 0.05.

(4) other ingredients

In addition to the above components, the oral pharmaceutical composition of the present invention may contain various drugs and additives usable in oral medicines within a range that does not impair the effects of the present invention.

Examples of the drug include antipyretic analgesics, antihistamines, antitussive expectorants, antacids, vitamins, minerals and the like.

Specifically, for example, aspirin, acetaminophen, ibuprofen, ethenamide, naproxen, diclofenac sodium, pyoxycamp, azulene, indomethacin, salicylic acid, ketoprofen, isosorbide nitrate, and dihydrocodein phosphate And ephedrine and salts thereof, phenylpropanolamine hydrochloride, chlorpheniramine maleate, theophylline, (anhydrous) caffeine, cephalexin, sulfisoxazole, minerals, thiamine, ascorbic acid (salts), and the like.

Examples of the additive include excipients, disintegrants, binders, sweeteners other than scalose, pigments, flavors other than grapefruit flavoring agents, lubricants, and the like, which are commonly used in the field of medicine.

Examples of the excipient include sugars such as lactose, sugar alcohols such as sorbitol, mannitol, maltitol, erythritol and xylitol, starch such as corn starch, silicon dioxide and the like. Among them, the use of sugar alcohols is preferred because the effect of the present invention becomes better. Particularly preferred sugar alcohol is erythritol.

Examples of the disintegrating agent include croscarmellose, crospovidone, low-substituted hydroxypropyl cellulose, crystalline cellulose, and the like.

Examples of the binder include hydroxypropyl cellulose, polyvinyl alcohol, polyvinylpyrrolidone, alpha starch and the like.

As sweeteners other than scalose, for example, acesulfame potassium, tomate, aspartame, stevia and the like can be used within a range that does not impair the effect of the present application.

Examples of the pigment include zinc oxide, titanium dioxide, and various colored pigments that can be blended into oral medicines.

Arbitrary fragrances other than grapefruit fragrance can use the fragrance which is compatible with grapefruit flavor in the range which does not impair the effect of this application. As said fragrance | flavor, mint type fragrances, such as peppermint, spearmint, and mint, menthol, a carbon, etc. are mentioned.

Examples of the lubricant include calcium stearate, magnesium stearate, and the like.

(5) formulation, preparation method

Although the oral pharmaceutical composition of this invention can be made into solid preparations, such as a tablet and a granule, a liquid preparation, a jelly agent, etc., a solid preparation is preferable. As a tablet, it is preferable to set it as the formulation taken without water, such as a chewable tablet, an intraoral disintegrating tablet, an intraoral dissolving tablet, and a troche.

Examples of the granular agent include powders, fine granules, and granules, which are well known in the field of medicine.

The manufacturing method of each formulation is not specifically limited, It can manufacture by a well-known method. For example, a granular agent can mix and obtain each component, and may use granulated particle as needed. In the case of refining, it can obtain by applying well-known methods, such as mixing each component (you may use a usual granulated particle as needed), and tableting with a tableting machine.

[Example]

Below, the oral composition of this invention is demonstrated using an Example.

<Test Example 1>

Each component was weighed by the prescription of Table 1, and it stirred and mixed so that each component may uniformly disperse | distribute, and prepared the oral preparation (granule) of 1000 mg of whole quantity.

The presence or absence of the unpleasant taste of the oral preparation and the aftertaste of the sweetener of the sweetener were evaluated by the trained flavor technician on the following criteria.

(Evaluation standard)

Presence of throat irritation

◎: do not feel throat irritation.

(Circle): It feels a little throat irritation.

(Triangle | delta): A strong throat irritation is felt.

X: The throat irritation is felt very strongly.

Presence of unpleasant taste

◎ I do not feel unpleasant taste.

○ I feel some unpleasant taste.

△ I feel slightly unpleasant taste.

× I feel an unpleasant taste strongly.

Aftertaste of sweetness

◎ I do not feel the aftertaste of sweetness.

○ I feel a little aftertaste of sweetness.

△ I feel a little strong aftertaste.

× I feel a strong aftertaste of sweetness.

Sample No 1-1 1-2 Ibuprofen 12 12 Scralose 1.2 1.2 Grapefruit Spice Particles (* 1) 0.4 0 Excipients (crystalline cellulose: D-mannitol: lactose = 1: 2: 2) Remainder Remainder system 100 100 Throat Stimulation ◎ △ Presence of unpleasant taste ◎ ◎ Aftertaste of sweetness ◎ ×

(* 1) Product name "powder flavor SY-1521"

 `` Powder fragrance SY-1521 '' grapefruit fragrance (containing 84.0 mass% of limonene and 0.245 mass% of nut carton) 25 mass% AI

<Test Example 2>

The tablet of the prescription shown in Table 2 was manufactured, and the presence or absence of the unpleasant taste and the aftertaste of the sweetener of the sweetener were evaluated like Test Example 1.

Sample No 2-1 2-2 2-3 Ibuprofen 65 65 65 Acetoaminophen 65 65 65 Caffeine 40 40 40 Arylisopropylacetylurea 30 30 30 Scralose 3.4 Acesulfame Potassium 10.2 Grapefruit Spice Particles (* 1) 1.12 1.12 1.12 Lactose Remainder Remainder Remainder Erythritol 15 15 15 Low Substitution Hydroxypropyl Cellulose 35 35 35 Hydroxypropylcellulose 6 6 6 Magnesium Stearate One One One System (mg / tablet) 280 280 280 Throat Stimulation ◎ × × Presence of unpleasant taste ◎ ○ × Aftertaste of sweetness ◎ ◎ ◎

(* 1) Product name "powder flavor SY-1521"

 `` Powder fragrance SY-1521 '' grapefruit fragrance (containing 84.0 mass% of limonene and 0.245 mass% of nut carton) 25 mass% AI

<Test Example 3>

The granules of the prescription of Tables 3 and 4 were produced, and the presence or absence of an unpleasant taste and the aftertaste of sweetness were evaluated similarly to Test Example 1.

Sample No 3-1 3-2 Ibuprofen 150 150 Caffeine Anhydrous 25 25 d1-methyl hydrochloride 20 20 Phosphate Dihydrocodeine 7 7 Male chlorpheniramine 2.5 2.5 Vitamin B1 7 7 Vitamin C 170 170 Scralose 12 Acesulfame Potassium 36 Grapefruit Spice Particles (* 1) 4 4 Lactose Remainder Remainder Mannitol 130 130 Erythritol 170 170 Crystalline cellulose 150 150 Silicon dioxide 10 10 Low Substitution Hydroxypropyl Cellulose 70 70 Hydroxypropylcellulose 50 50 System (mg / sachet) 1000 1000 Throat Stimulation ◎ × Presence of unpleasant taste ◎ ○ Aftertaste of sweetness ◎ ◎

(* 1) Product name "powder flavor SY-1521"

`` Powder fragrance SY-1521 '' grapefruit fragrance (containing 84.0 mass% of limonene and 0.245 mass% of nut carton)

Claims (7)

An oral pharmaceutical composition comprising ibuprofen, scalose and grapefruit flavorings. The method of claim 1,
Oral pharmaceutical composition, characterized in that the mass ratio of the scalose and grapefruit flavoring (Scralose / Grapefruit flavoring) is 1 / 0.01 to 1/1 (= 100 to 1). The method of claim 1,
Oral pharmaceutical composition, characterized in that the mass ratio of ibuprofen and scalose (Ibuprofen / Scralose) is 1 / 0.01 to 1 / 0.5 (= 100 to 2). The method of claim 1,
An oral pharmaceutical composition, wherein the mass ratio (ibuprofen / Scralose / Grapefruit flavoring) between ibuprofen, scalose, and grapefruit flavoring is 1 / 0.1 / 0.01 to 1 / 0.5 / 0.05. The method of claim 1,
The content of ibuprofen is 5 to 80% by mass in the composition, the content of scalose is 0.01 to 10% by mass in the composition, and the content of grapefruit flavor is 0.01 to 2% by mass in the composition. The method of claim 1,
Moreover, oral pharmaceutical composition containing sugar alcohol. A granular agent, orally disintegrating tablet or troche comprising the oral pharmaceutical composition according to claim 1.