JP2000095675A - Oral solid pharmaceutical composition for treating rhinitis of intraoral soluble type or mastication type - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject composition enabling the rapid reaching of an administered treating agent for rhinitis to an inflammatory site to act on it and, at the same time, imparting the sure durability of the activity and high bioavailability to it by including the agent. SOLUTION: This composition is obtained by including a treating agent for rhinitis. Preferable examples of the treating agent for rhinitis include (A) a parasympatholytic agent, (B) an antihistaminic agent, (C) a sympathomimetic drug, (D) an antiallergic agent, (E) an antiinflammatory agent, (F) an antiinflammatory enzyme and the like. Examples of the components are as follow: a belladonna (gross) alkaloid, isopropamide iodide and the like as the component A; isothipendyl hydrochloride, diphenhydramine and the like as the component B; phenylpropanolamine hydrochloride, phenylephrine hydrochloride and the like as the component C; astemizole, cycloheptadine hydrochloride and the like as the component D; glycyrrhizic acid, KANZOU (root of Glycyrrhiza glabra) and the like as the component E; and lysozyme chloride, bromelain and the like as the component F.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a solid oral pharmaceutical composition for treating nasal inflammation of the oral dissolution type or chewable type, which has immediate action and long-lasting properties.

[0002]

2. Description of the Related Art Although the entrance of a nose (nostril) is small, there is a large space (nasal cavity) covered with mucous membrane at the back, and the nasal cavity is further connected to the pharynx at the back. Rhinitis is a condition in which the mucous membrane of the nasal cavity is inflamed for some reason, and the main causes include allergies and infections caused by viruses and bacteria. In recent years, the number of patients suffering from allergic rhinitis due to hay fever and house dust has been increasing. In addition, patients who exhibit rhinitis as one of the various symptoms of the so-called "cold" such as influenza and colds caused by viruses and the like are not extinct. Usually, the representative cause of chronic rhinitis is allergy. However, when the treatment of "cold" is incomplete, there are cases where rhinitis is not cured and the disease is changed to chronic rhinitis. In addition, in patients with “cold”, rhinitis may be exacerbated by resident bacteria such as staphylococci and streptococci because the nasal self-purifying effect is reduced due to viral infection or the like. Although there are various causes as described above, specific symptoms common to rhinitis include nasal discharge, nasal congestion, sneezing, nasal itch, tears, and sore throat. The nasal congestion symptom is caused by swelling of the mucous membrane of the nose and narrowing of the nasal cavity, which may be accompanied by dyspnea and heavy head. Also, nasal secretions themselves cause discomfort, but can cause inflammation of the nasal cavity by frequent chewing of the nose. Watery eyes are symptoms caused by increased secretion of tears.

[0003] Many patients with rhinitis develop the above-mentioned unpleasant symptoms more than once, repeatedly or chronically. If such a state persists for a long period of time, the quality of life (QOL) of the patient will be reduced, and daily life will be hindered. These rhinitis symptoms, especially nasal congestion and increased nasal discharge, can cause intolerable discomfort, and rhinitis patients tend to urge for an immediate and effective treatment. Therefore, there has been a strong demand for the development of a pharmaceutical preparation which is not only effective in alleviating the symptoms of total rhinitis, but also has an immediate effect and a long lasting effect in which the effect of suppressing nasal discharge and improving the nasal congestion is enhanced. 2. Description of the Related Art Conventionally, drug treatments for rhinitis are mainly administered as oral oral preparations or nasal drops of drugs such as antihistamines, sympathomimetics (vasoconstrictors), parasympathetic blockers, anti-inflammatory drugs, and anti-inflammatory enzymes. It is done by that.

[0004]

A nasal drop is expected to have an immediate effect on nasal congestion since a drug is sprayed or dropped into a nasal cavity directly from a nostril to reach a mucous membrane directly. However, in case of excessive nasal discharge, the nasal discharge is pushed out from the nasal cavity toward the nostril due to the physiological function of the nasal cavity, so that the drug may not be able to reach the nasal cavity effectively. In addition, it does not show sufficient effects in terms of sustained effects and relief of nasal discharge, head weight and tears. On the other hand, oral preparations are useful in terms of long-lasting effects and treatment of nasal congestion, nasal discharge, headache, sore throat, and teary eyes, but cannot be expected to have immediate effect. A soft capsule for rhinitis is provided as a better immediate-acting solid preparation for internal use, but this preparation also reaches the stomach quickly after taking it, so it has no direct effect on the nasal cavity and it shows immediate effect. Can not. In addition, since oral solid preparations are generally absorbed via the digestive tract and act locally, the expression of the effect fluctuates due to the influence of the content of the meal, and not only a certain effect can not be expected, but also administered. Only a small part of the drug reaches the target site (nasal cavity) and only exerts its effect. There is also a problem in terms of effective use of the drug. Therefore, the administered drug quickly reaches the site of inflammation and acts,
There has been a demand for the development of a pharmaceutical composition capable of reliably maintaining its action, having a high bioavailability and maximizing the effect of a drug.

[0005]

DISCLOSURE OF THE INVENTION The present inventors have enthusiastically aimed at providing an effective solid oral pharmaceutical composition for the treatment of rhinitis, which has an immediate effect and a reliable sustainability for the treatment of rhinitis symptoms. As a result of repeated studies, it has been found that, when the same amount of active ingredient is allowed to act, it can achieve not only immediate effect and sustainability of the effect but also high bioavailability when it is made into a mouth-soluble or chewable form. As a result, the present invention has been completed. That is, the present invention provides a solid pharmaceutical composition for treating rhinitis of the oral dissolution type or mastication type, which comprises a therapeutic agent for rhinitis.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The pharmaceutical composition for the treatment of oral dissolving or masticatory rhinitis of the present invention is a preparation which is dissolved or dissolved in the oral cavity in the presence of saliva, instantaneously or gradually, or which is chewed, pulverized and saliva Is a preparation to be taken after dissolving a part or the whole thereof by mixing with the above, and refers to a pharmaceutical composition used for treatment of rhinitis symptoms associated with colds such as allergy, influenza and common cold. As shown in the test examples described below, the oral dissolving or chewable pharmaceutical composition of the present invention is compared with a case in which the same amount of a therapeutic agent for rhinitis is taken as an oral tablet without dissolving or chewing in the mouth. It has unexpectedly good therapeutic effects. As described above, the enhancement of the therapeutic effect of rhinitis according to the present invention effectively eliminates all rhinitis symptoms including nasal congestion, nasal discharge, head weight, tears, and sore throat for a long time immediately after administration. can do. This excellent effect is a symptom in a site where rhinitis is in close contact with the oral cavity, and is dissolved in saliva in the process of dissolving and / or chewing the pharmaceutical composition of the present invention in the mouth, thereby promoting drug elution. A part of it acts directly from the pharynx to the local part of the nasal cavity to exert immediate effects, reaches the absorption site in a state that it is easily absorbed as a mixture with saliva, and is absorbed from the digestive tract while maintaining stability and high It is related to being able to exhibit effects.

[0007] The pharmaceutical composition of the present invention can contain any known drug for treating rhinitis, except for drugs that are not suitable for dissolving or chewing in the mouth. Examples of such rhinitis treatment agents include parasympathetic blockers, antihistamines, sympathomimetics, antiallergic agents, antiinflammatory agents and anti-inflammatory enzymes, and when preparing the pharmaceutical composition of the present invention, And one or more drugs selected therefrom.
When a plurality of drugs are used, the drugs may be of the same type (when classified by action) or may be of different types. Usually, rhinitis patients often present with a plurality of symptoms such as nasal congestion, nasal discharge, weight of the head, and tearing eyes.
It is preferable to use a combination of two or more drugs.

[0008] The parasympathetic blocker used in the present invention includes:
It is a drug having mucus secretion inhibitory effect and nasal secretion inhibitory effect based on blocking anti-acetylcholine action, and is useful for nasal secretion inhibition. For example, datsura extract, belladonna alkaloid, belladonna total alkaloid, belladonna extract, funnel extract, isopropamide iodide and the like are exemplified, belladonna alkaloid, belladonna total alkaloid, belladonna extract, roth extract, isopropamide iodide are preferable, belladonna alkaloid, belladonna total alkaloid And isopropamide iodide are more preferred. These can be used alone or in combination of two or more. Although parasympathetic blockers have the side effect of dry mouth due to suppression of salivary secretion, the effect per dose is higher than in the case of oral administration by dissolving or chewing in the mouth, resulting in immediate effect and high biological effect. As a result, it is possible to avoid the occurrence of side effects.

[0009] Parasympathetic blockers are usually administered to an adult in an amount of 0.01 to 10 parts per day as an active ingredient.
100 mg can be administered. For example, in the case of belladonna alkaloid, 0.01 to 1 mg, and in the case of a funnel extract, belladonna extract, and datsura extract, 1 to 100 m
g, in the case of isopropamide iodide, 0.1 to 10 mg can be orally administered once or several times a day. In the case of the composition of the present invention, the effect per dose can be enhanced, so that the dose can be reduced. Therefore, in the case of belladonna alkaloids, 0.1 to 0.6 mg, and in the case of funnel extract, belladonna extract and datsura extract, 10 to 60 m
g, isopropamide iodide is effective even in the range of 1 to 8 mg, and this range is preferable from the viewpoint of avoiding side effects such as dry mouth. However, the dose can be appropriately increased or decreased according to the age, weight, or medical condition of the patient, and is not limited to the above range.

[0010] Antihistamines are drugs that block the action of histamine.
Iproheptin hydrochloride, dipheterol hydrochloride, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, diphenhydramine hydrochloride, triprolidine hydrochloride, tripelenamine hydrochloride, tondylamine hydrochloride, promethazine hydrochloride, methdilazine hydrochloride, diphenhydramine salicylate, carbinoxamine diphenyldisulfonate, alimimazine tartrate, diphenamine diphenylamine tannate , Carbinoxamine maleate, chlorpheniramine maleate (d-form, dl-form), promethazine methylene disalicylate or salts thereof.
More than one species can be used in combination. Examples of the salts include hydrochloride, maleate, tartrate, salicylate, tannate, diphenyldisulfonate, theocleate, and methylene disalicylate. Preferred antihistamines are isotipendyl hydrochloride, iproheptin hydrochloride, diphenhydramine hydrochloride, diphenhydramine, alimemazine tartrate, diphenhydramine tannate and chlorpheniramine maleate (d-form, dl-form), or salts thereof. The antihistamine is usually administered to an adult in a daily dose of 1 to 200 mg, preferably 1 to 100 mg, but the appropriate amount varies depending on the drug. For example, diphenhydramine hydrochloride has an appropriate amount of 1 to 100 mg, and chlorpheniramine maleate (dl form) has an appropriate amount of 1 to 10 mg, which can be appropriately used depending on the drug.

[0011] As antiallergic drugs, astemizole,
Cycloheptadine hydrochloride, terfenadine, ibudilast, oxatomide, amlexanox, tranilast,
Ketotifen, azelastine, sodium cromoglycate, repirinast, emedastine, mequitazine, ozagrel, tazanolast, pemirolast, clemastine fumarate, alimemazine, epinastine, suplatast and the like, or a salt thereof, and the like, or a combination of two or more can be used. . Examples of the salts include hydrochloride, maleate, tartrate, salicylate, tannate, diphenyldisulfonate, theoclate, methylenedisalicylate, nitrate, fumarate and the like. Preferred antiallergic agents include astemizole, cycloheptadine hydrochloride, amlexanox, ketotifen fumarate, azelastine hydrochloride, sodium cromoglycate, mequitadine, clemastine fumarate, epinastine hydrochloride, tranilast, emedastine fumarate, oxatomide, pemirolast potassium and alimemazine, Or salts thereof. Antiallergic drugs are usually administered to adults at a daily dose of 0.1%.
The dosage is from 01 to 300 mg, and the appropriate amount varies depending on the drug, and it can be appropriately used within the usual range.
For example, astemizole is 2.5-5 mg, ketotifen fumarate is 0.2-5 mg, and epinastine hydrochloride is 2-3.
0 mg, mequitazine 0.5 to 15 mg, and alimemazine tartrate 2 to 15 mg.

As sympathomimetics (vasoconstrictors), phenylpropanolamine hydrochloride, phenylephrine hydrochloride,
Drugs such as methylephedrine hydrochloride, methoxyphenamine hydrochloride, epinephrine, ephedrine hydrochloride, norepinephrine, naphazoline nitrate, gyrometazoline, midodrine, methoxamine, tetrahydrozoline hydrochloride and the like, and salts thereof, and the like, alone or in combination of two or more Can be. Examples of the salts include hydrochloride, maleate, tartrate, salicylate, tannate, diphenyldisulfonate, theoclate, methylene disalicylic acid, and nitrate. As salts, hydrochloride, maleate,
Tartrate, salicylate, tannate, diphenyldisulfonate, theoclate, methylene disalicylate,
There are nitrates and the like. Preferred sympathomimetics (vasoconstrictors) are phenylpropanolamine hydrochloride, phenylephrine hydrochloride and methoxyphenamine hydrochloride, methylephedrine hydrochloride or salts thereof. Sympathomimetics (vasoconstrictors) are usually given as a daily dose to adults of 1-3.
00 mg, preferably 1 to 150 mg, the appropriate amount varies depending on the drug, for example, 1 to 120 mg for phenylpropanolamine hydrochloride, 1 to 40 mg for phenylephrine hydrochloride, 1 to 40 mg for methylephedrine hydrochloride. If the dose is 125 mg and methoxyphenamine hydrochloride, the dose is 1 to 175 mg.

[0013] Examples of the anti-inflammatory enzyme include lysozyme chloride, bromelain, α-chymotrypsin, semi-alkaline proteinase (seaprose S-AP), proteinase, serratiopeptidase (serrapeptidase), streptokinase, and strepdornase. Preferred anti-inflammatory enzymes are semi-alkaline proteinases, lysozyme chloride, bromelain and serrapiopeptidase (serrapeptidase). The anti-inflammatory enzyme is usually administered to an adult at a daily dose of 1.0 to 200 mg, preferably 1 to 100 mg. The appropriate amount varies depending on the drug, and can be used as appropriate within the usual range.
For example, in the case of lysozyme chloride, the range of 1 to 100 mg is appropriate.

The anti-inflammatory drug includes glycyrrhizic acid, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, diammonium glycyrrhizinate and salts thereof, as well as licorice and tranexamic acid. These may be used alone or in combination. Can also. The anti-inflammatory drug is usually administered to an adult in a daily dose of 0.1 to 300 mg as glycyrrhizic acid. The appropriate amount varies depending on the drug, and can be appropriately used within the usual range.

When a central nervous system stimulant is added to the pharmaceutical composition of the present invention in addition to a therapeutic agent for rhinitis, the effect on head weight due to rhinitis is further enhanced, and it is also effective against drowsiness which is a side effect of certain therapeutic agents for rhinitis. In some cases, this is preferable because it contributes to the improvement of the overall therapeutic effect. Examples of the central nervous system stimulant include caffeines, and specific examples thereof include anhydrous caffeine, caffeine, sodium benzoate caffeine, and the like. The dose is preferably 12 to 300 mg per day for an adult. More preferably, 10
0-200 mg.

In the composition of the present invention, menthol, cinerol and camphor can be used together. As shown in the test examples described below, it is preferable to include menthol, because in addition to the improvement of compliance, the immediate effect is further remarkably enhanced. Menthol may be used as menthol or as an essential oil containing menthol such as peppermint oil, spearmint oil, peppermint oil, and mint oil. The dose of menthol is usually in the range of 0.001 to 40 mg per day for an adult. The preferred concentration of menthol in the composition is between 0.1 and 2.2.
It is 25% by weight, and if it is in this range, it gives a refreshing refreshing feeling without bitterness and is effective in improving patient compliance. When it exceeds this range, menthol stimulation may be unpleasant. . Menthol is described in the literature (13th revised Japanese Pharmacopoeia, D1050 to 1058), and commercially available menthol can also be used. Any of natural essential oil-derived and synthetic products may be used. When used in the composition of the present invention, menthol is
It may be either a body or a dl body. Cinerol and camphor are both described in the Japanese Pharmacopoeia, and commercially available ones can also be used. Cinerol is contained in a large amount in eucalyptus oil, and may be used as cinelol or eucalyptus oil. A large amount of camphor is contained in camphor oil, and may be used as camphor or camphor oil. In addition, since the composition of the present invention, which is a dosage form that dissolves and / or chews in the mouth, has a long residence time in the mouth and the drug comes into direct contact with the taste buds, it is necessary to consider the effect on taste and smell. preferable. From that perspective,
Essential oils containing menthol, camphor and cinerol,
When used together with fruit flavors, it helps to improve patient compliance. This is preferred, particularly when using a bitter-tasting drug, as it allows masking of it.

The composition of the present invention can contain any medicinal ingredient according to the purpose of the present invention, and is not limited to the above-mentioned drugs. In addition, other substances (pharmaceuticals or quasi-drugs) commonly used in the art may be added as long as the therapeutic effect of the rhinitis condition is not impaired. Such substances include vitamins, crude drugs, antitussives, expectorants, sputum lytics, antipyretic analgesics, antacids and the like. Combining components for cold medicine is useful for treating rhinitis associated with cold.

The above-mentioned other components are each compounded within the range of the usual dose. As crude drugs,
Keigai, Saishin, Tokyo, Shiny, Zenko,
Anti-tussives such as codeine phosphate, dextrometrophanes, etc .; expectorants such as guaifenesin and potassium guaiacol sulfonate; sputum dissolving agents such as lysozyme chloride and cysteine; Examples of antacids such as phen, ethenzamide, and aspirin include magnesium silicate, magnesium oxide, and magnesium hydroxide.

The pharmaceutical composition of the present invention may be in any form as long as it is taken by dissolving or chewing in the mouth, and tablets (uncoated tablets, dragees), candy (candy), gummy preparations, nougat And the like. The shape and size are appropriately selected within a range not inconvenient for taking in the mouth. Tablets are prepared by mixing a powdered drug with a pharmaceutically acceptable excipient and compression-molding. Candies (candy), gummy preparations, nougat preparations, and the like are prepared by methods known in the confectionery field. Can be prepared. For example, tablets are extruded granulation methods, pulverization granulation methods, dry compaction granulation methods, fluid bed granulation methods, tumbling granulation methods, high-speed stirring granulation methods, wet tableting methods known in the art, What is necessary is just to manufacture by directly combining the direct compression method etc. according to the objective. Preferred dosage forms for the practice of the present invention are
Tablets, especially chewable tablets which are taken by chewing in the mouth.

The preparation of the present invention may contain any component generally used as an excipient as long as the effects of the present invention are not affected. As such additives, corn starch, potato starch, sucrose, talc, kaolin, calcium sulfate, calcium carbonate, excipients such as crystalline cellulose, lubricating agents such as magnesium stearate, calcium stearate, carboxymethylcellulose calcium, Disintegrators such as hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, gelatin, cellulose polymers, acrylic polymers, methylcellulose, gum arabic, binders such as polyvinyl alcohol, and other sweeteners, Flavoring agents, coloring agents, flavoring agents, adsorbents, preservatives, wetting agents, antistatic agents and the like can be mentioned. In addition, the composition of the present invention can control the release of a drug in accordance with the purpose, thereby controlling the manifestation of a pharmacological effect, and can provide a more durable preparation.

[0021]

The present invention will be described in more detail with reference to the following examples. Example 1 Tablet

[Table 1] Tablets were prepared according to the Japanese Pharmacopoeia General Rules for Preparations “Tablets”. Specifically, the components from d-chlorpheniramine maleate to mannitol are taken, and granules (A) are prepared by a wet granulation method. On the other hand, menthol and Avicel are mixed to prepare menthol trituration (B). Next, the granules (A), menthol trituration (B), and magnesium stearate were mixed to obtain granules for tableting.
Tablets were prepared on a tableting machine as mg / tablet.

Example 2 Tablet

[Table 2] As in Example 1, granules (A) were prepared using components from diphenhydramine hydrochloride to xylitol, while components from Avicel to peppermint oil were mixed,
Menthol trituration (B) was prepared to produce a tablet of 300 mg per tablet.

Example 3 Tablet

[Table 3] In the same manner as in Example 1, a granule (A) is prepared using components from diphenhydramine salicylate to mannitol, while a component from Avicel to mint oil or peppermint oil is mixed to obtain menthol trituration (B). Prepared, 1 tablet 40
0 mg tablets were made.

Example 4 Tablet

[Table 4] In the same manner as in Example 1, granules (A) were prepared using components from clemastine fumarate to sorbit.
Menthol trituration (B) was prepared from HPC and menthol to produce a tablet of 250 mg per tablet.

Example 5 Tablet

[Table 5] In the same manner as in Example 1, granules (A) are prepared using the components from mequitazine to mannitol, while the components from Avicel to mint oil or mint oil are mixed to prepare menthol trituration (B). Then, a tablet of 500 mg per tablet was produced.

Example 6 Tablet

[Table 6] As in Example 1, granules (A) were prepared using components from ketotifen fumarate to sorbit, while L-
Menthol trituration (B) was prepared from HPC and menthol to produce a tablet of 250 mg per tablet.

[0027] Mix the above ingredients and add 1.5g per piece as usual
(Dose: 3 per day) candy was made.

Example 8 nougat d-chlorpheniramine maleate 6.0 parts phenylpropanolamine hydrochloride 90.0 caffeine 60.0 sugar 2677.2 starch syrup 210.0 expanded gelatin (50% gelatin) 390.0 vegetable Oils and fats 54.0 Pigment 5.4 Menthol 12.0 Grapefruit essence 5.4 540.0 The above ingredients are mixed, and 1.8g per piece is mixed as usual.
(Dose: 3 per day) nougat was produced.

Example 9 Gummy Diphenhydramine hydrochloride 50.0 parts Phenylpropanolamine hydrochloride 90.0 Caffeine 60.0 Powdered gelatin (180 bloom) 430.5 Sugar 120.0 Sugar cane 12000.0 Menthol 15.0 Lemon oil 4. 5 Hot water 1450.0 4500.0 The above ingredients are mixed together and, as usual, 1.5 g per piece
Gums (dose: 3 per day) were made.

Example 10 Gum d-Chlorpheniramine maleate 6.0 parts Verazonena total alkaloid 0.4 Caffeine 60.0 Gum base 210.0 Sugar 4656.8 Glucose 90.0 Corn syrup 120.0 Glycerin 55.8 Menthol 12.0 Peppermint oil 9.0 900.0 Mix the above ingredients and 3.0g per sheet as usual
(Dose: 3 per day) gum was made.

Test Example 1 Dissolution Test Using the chewable tablet of Example 1 and a commercially available oral preparation for rhinitis,
Dissolution test (paddle method), a general test method of the Japanese Pharmacopoeia
The test was performed according to As a test solution, using purified water, in a test solution 500 ml, at 37 ° C., the paddle rotation speed 100 rpm
Went as. The chewable tablet of Example 1 has about 5
, And added to the test solution as a sample. After the test was started, the eluate was collected over time, and the elution amount of the drug was measured using chlorpheniramine maleate contained in the chewable tablet as an index component. As controls, commercially available hard capsules (commercially available product 1), tablets (sugar-coated tablets) (commercially available products 2), granules (commercially available products 3), and soft capsules (commercially available products) containing chlorpheniramine maleate as an active ingredient These were tested without mastication using 4). Chlorpheniramine maleate was measured by a conventional HPLC method. Table 7 shows the results.

[0032]

[Table 7] nd: below the detection limit On the other hand, using a test solution of pH 1.2 assuming gastric juice or pH 6.8 assuming intestinal fluid in a disintegration test, which is a general test method of the Japanese Pharmacopoeia, A drug dissolution test was performed on the granules (commercial product 3) in the same manner as described above. Table 8 shows the results.

[0033]

[Table 8]

From Tables 7 and 8, it can be seen that the elution of the drug from the chewable tablet of Example 1 is extremely rapid and complete elution in a short time (almost 100%). Its dissolution rate is superior to that of granules having a large surface area (commercial product 3). Also, from Table 8, it can be seen that the dissolution from the chewable tablet of Example 1 was not affected by the pH at all. It is considered that the elution of the drug is promoted by the increase of the surface area by mastication, however, compared with the granules of the commercial product 3, the dissolution in the stomach (pH
= 1.2) and in the mouth (pH = 6.8), the composition of the present invention shows a superior drug dissolution effect. This suggests that the promotion of dissolution in the composition of the present invention is not caused solely by the increase of the surface area by chewing. The rate of drug release and its fluctuation are closely related to the rate and amount of drug absorption in the gastrointestinal tract, and are known to have a great effect on the onset of drug treatment effects. The above test results reveal that the formulation of the present invention shows an excellent dissolution rate as compared with the conventional formulation, and the formulation of the present invention has immediate effect and high bioavailability, It proves that it is a useful preparation that can surely exert a high effect continuously.

Test Example 2 Effectiveness test

[Table 9] Tablets A-1 to D shown in Table 9 were prepared in the same manner as in Example 1. As a control, a tablet E containing only menthol was prepared in the same manner and used for the test. All of these preparations have a content test, a disintegration test (JP), and a content uniformity test (J
P). Rhinitis symptoms (sneezing,
The drug was administered (one tablet at a time) to 14 subjects having runny nose, congestion in the nose, sore throat, tears, and head weight, and the degree of improvement in symptoms was evaluated 10 minutes and 4 hours after taking the drug. Tablet A-
1, B and E were chewed (5 to 15 times) in the mouth and taken, and tablet A-2 was dissolved and taken without chewing. Also,
Tablets C and D were swallowed with 150 ml of water without chewing or dissolving in the mouth. The test results are shown in Tables 10 and 11.

[0036]

[Table 10]

[0037]

[Table 11]

The tablets A-1, A-2 and B of the present invention are
Compared to non-chewable and non-dissolvable tablet C, the improvement rate after 10 minutes is significantly higher and the improvement rate after 4 hours is also excellent, indicating that it has both immediate effect and sustainability. . In addition, these preparations A-1, A-2 and B of the present invention
Is much more effective than the composition of menthol alone, both after 10 minutes and after 4 hours, when compared with Tablet E containing no drug other than menthol (take by chewing). On the other hand, non-chewing, non-dissolving tablet C
And D have a low improvement rate regardless of the presence or absence of menthol.
Further, when the chewing type (A-1) and the dissolving type (A-2) preparations containing menthol are compared with the mastication type (B) preparation containing no menthol, the former two are much higher in immediate effect than the latter. This can be seen (see Table 10). This indicates that when menthol is contained in the chewable or dissolvable preparation, the immediate effect is significantly enhanced. From the above results, it is clear that the dissolvable or chewable preparation of the present invention is more immediate and has a longer lasting effect on rhinitis symptoms than ordinary swallowable tablets. Even after 4 hours from the administration, the composition of the present invention has a high effect and a high bioavailability. It can be said that this is a preparation. The following points are considered as causes of these excellent effects. 1. Because it is mixed with saliva in the mouth, drug dissolution is promoted. 2. Immediate absorption and increased absorption. 3. The movement of the jaw promotes blood circulation in the nasal cavity. 4. There is a direct action of the nasal cavity from the pharynx.

[0039]

The pharmaceutical composition of the present invention can act on the nasal mucosa directly from the pharynx because it is retained in the mouth for a long time and is mixed with saliva, so that any type of rhinitis including nasal discharge is possible. Shows immediate effect on This immediate effect is effective not only in nasal congestion but also in alleviating various symptoms of rhinitis such as nasal discharge, head weight and sore throat. At the same time, it is also absorbed from the gastrointestinal tract, can reliably exert a sustained effect, and can achieve a sufficiently high bioavailability as compared to ordinary oral tablets containing the same amount of active ingredient . As a result, the effective use of the drug becomes possible, and the burden on the patient can be reduced and the quality of life can be improved through reduction of the dose.

Claims (16)

[Claims] 1. A solid oral pharmaceutical composition for the treatment of rhinitis, which comprises a drug for the treatment of rhinitis. 2. The method according to claim 1, wherein the drug for treating rhinitis is one or more drugs selected from parasympathetic blockers, antihistamines, sympathomimetics, antiallergic drugs, antiinflammatory drugs and anti-inflammatory enzymes. Pharmaceutical composition. 3. The pharmaceutical composition according to claim 2, wherein the parasympathetic blocker is selected from datura extract, belladonna alkaloid, belladonna total alkaloid, belladonna extract, funnel extract and isopropamide iodide. 4. The pharmaceutical composition according to claim 3, wherein the parasympathetic blocker is selected from belladonna alkaloids, belladonna total alkaloids, and isopropamide iodide. 5. The antihistamine drug is isotipendyl hydrochloride, iproheptin hydrochloride, dipheterol hydrochloride, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, diphenhydramine hydrochloride, triprolidine hydrochloride, tripelenamine hydrochloride, tondylamine hydrochloride, promethazine hydrochloride, methdilazine hydrochloride, diphenhydramine salicylate, diphenyldisulfonic acid. Carbinoxamine, alimemazine tartrate,
3. The pharmaceutical composition according to claim 2, which is selected from diphenhydramine tannate, diphenylpyraline teoclate, carbinoxamine maleate, chlorpheniramine maleate (d-form, dl-form), and promethazine methylene disalicylate. 6. The method of claim 1, wherein the antihistamine is isotipendyl hydrochloride,
Iproheptin hydrochloride, diphenhydramine hydrochloride, diphenhydramine, alimemazine tartrate, diphenhydramine tannate and chlorpheniramine maleate (d
Or a dl-form) or a salt thereof. 7. The sympathomimetics include phenylpropanolamine hydrochloride, phenylephrine hydrochloride, methylephedrine hydrochloride, methoxyphenamine hydrochloride, epinephrine, ephedrine hydrochloride, norepinephrine, naphazoline nitrate, gyrometazoline, midodrine, methoxamine and tetrahydrozoline hydrochloride, or a combination thereof. The pharmaceutical composition according to claim 2, which is selected from salts of 8. The pharmaceutical composition according to claim 7, wherein the sympathomimetics are selected from phenylpropanolamine hydrochloride, phenylephrine hydrochloride, methylephedrine hydrochloride and methoxyphenamine hydrochloride, or salts thereof. 9. The antiallergic agent is astemizole, cyproheptadine hydrochloride, terfenadine, ibudilast, oxatomide, amlexanox, tranilast, ketotifen, azelastine, sodium cromoglycate, repirinast, emedastine, mequitazine, ozagrel,
Tazanolast, pemirolast, clemastine fumarate,
3. The pharmaceutical composition according to claim 2, which is selected from alimedazine, epinastine and suplatast, or salts thereof. 10. The antiallergic drug is astemizole, cyproheptadine hydrochloride, amlexanox, ketotifen fumarate, azelastine hydrochloride, sodium cromoglicate, mequitazine, clemastine fumarate and alimemazine, epinastine hydrochloride, tranilast, emedastine fumarate, oxatomide, pemirolast potassium 10. The pharmaceutical composition according to claim 9, which is selected from a salt thereof. 11. The pharmaceutical composition according to claim 2, wherein the anti-inflammatory drug is selected from glycyrrhizic acid and salts thereof, licorice and tranexamic acid. 12. The inflammatory enzyme is selected from lysozyme chloride, bromelain, α-chymotrypsin, semi-alkaline proteinase (seaprose S-AP), proteinase, serrapeptidase (serapeptidase), streptokinase and strepdornase. The pharmaceutical composition according to claim 2. 13. The pharmaceutical composition according to claim 12, wherein the anti-inflammatory enzyme is selected from semi-alkaline proteinase, lysozyme chloride, bromelain, and serrapeptidase (serrapeptidase). 14. The pharmaceutical composition according to claim 1, further comprising menthol, camphor or cinerol. 15. The pharmaceutical composition according to claim 1, further comprising caffeine. 16. A chewable oral preparation.
The pharmaceutical composition according to any one of the above.