JPH08337532A - Medicinal composition - Google Patents

Abstract

PURPOSE: To obtain a medicinal composition, capable of rapidly removing sputum and remitting the tussis and sputum symptoms and having high safety by blending a crude drug having promoting actions on the secretion of an airway mucilage with an airway mucilage consistency regulator and/or an airway mucosal membrane wetting agent. CONSTITUTION: This medicinal composition is obtained by blending (A) a crude drug having promoting actions on the secretion of an airway mucilage (preferably Senegae Radix or Platycod Radix, etc.) with (B) an airway mucilage consistency regulator (preferably an airway mucilage dissolvent such as N- aceylcysteine, an airway mucilage hardener such as sodium N-actylneuraminate) and/or (C) an airway mucosal membrane wetting agent (preferably ambroxol, etc.). The amount of the blended ingredient (A) is preferably 150-450mg expressed in terms of the daily dose for an adult and the dried extract in the case of the Senegae Radix (Pulverata). The amount of the blended ingredient (B) is usually 15-100mg in the case of the N-acetylcysteine and the amount of the blended ingredient (C) is preferably 15-45mg expressed in terms of the daily dose for an adult when using ambroxoal hydrochloride.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a pharmaceutical composition having an excellent action on sputum. More specifically, it relates to a composition for antitussive and expectorant having a wide range of application and having an expectorant action.

[0002]

2. Description of the Related Art Cough is caused mainly by a foreign substance invading the respiratory tract and an excessive secretion produced in response to the foreign substance, preventing the foreign substance from entering and making the mucus of the respiratory tract into sputum. It is said to be one of the so-called reflexive defense reactions of the living body that purifies the respiratory tract by letting it out. Cough
It is divided into wet cough with sputum and dry cough without sputum. The most common type of cough / sputum is generally the cold syndrome associated with acute inflammation of the upper respiratory tract due to viral infection. In this case, a so-called dry cough with less sputum usually recovers naturally in a few days,
In many cases, no particular treatment is required, and if the degree is so severe that it interferes with daily life, a cough medication will be used as symptomatic treatment. On the other hand, in so-called wet cough, which is a mixture of sputum and cough, which is often seen in general cold syndrome, it has the purpose of helping the sputum of sputum, so it is easier to stop coughing with an antitussive in terms of biological defense. It is said that the rapid and reliable removal of sputum is more important in the medical field.

Sputum is composed mainly of secretions from the trachea and bronchial mucosa, and cells exfoliated from the airway mucosa and aspirated foreign substances are mixed therein. Airway fluid production is 10-day
It is said to be 100 ml, and under physiological conditions, this liquid is not reabsorbed or swallowed and is not excreted. It is sputum that the airway fluid is increased in sputum beyond the physiological level for some reason such as inflammation of the airway, tumor or pulmonary congestion, and therefore any sputum should be regarded as abnormal. In many cases, sputum contains inflammatory exudates and pathogenic microorganisms of infectious diseases in addition to physiological secretion components. In a wet cough, if sputum is easily produced, the frequency of ejection is reduced, and therefore, expectorant is indirectly accompanied by an antitussive effect. It is said that the defense mechanism by the mucus factor and airway ciliary movement is involved in the expulsion of mucus in the respiratory tract due to the defense reaction of the living body. In wet cough, it is often the case that phlegm is viscous and sticks to the airway wall, and even if the cough is repeated, sputum will not be produced.In such cases, stopping the cough with an antitussive will cause sputum buildup, risk of choking or bacterial infection. There is a possibility that the property will increase. Therefore, in a moist cough, it may be more preferable for antitussiveness to promote sputum to eliminate passage obstruction in the airways. Speaking of sputum, it may become more viscous depending on the transition of the symptoms and stick to the walls of the respiratory tract, making it difficult to separate.On the other hand, since the mucolytic agent was taken at the onset of the initial symptoms, the viscosity became extremely low. Or, although the amount of airway fluid due to an expectorant drug was increased for the purpose of diluting sputum, sputum does not adapt well to water, and since it is not easily liquefied, the amount of water may become extremely large and the symptoms may worsen. It's a problem in the clinic. Thus, for sputum production, it may be easier for sputum to appear to some extent rather than a decrease in viscosity due to a mucolytic agent, so it is important to select a drug according to the phlegm symptom. Is.

Although such a cough / sputum symptom alone is unlikely to lead to a serious illness, it sometimes interferes with sleep or impairs food intake, which causes mental and physical exhaustion, and other respiratory organs. It is said that it is important to remove the disease as soon as possible because it may affect the exacerbation of diseases of the circulatory system. Conventionally, a therapeutic agent for cough / sputum symptom has been designed with the aim of stopping the cough, and various antitussive agents are used as main components. As such antitussives, narcotic codeines, non-narcotic but centrally acting drugs, and noscapine having a peripheral bronchodilator effect are used, but they have central side effects (for example, respiratory depression, sedation). ,sleepiness,
In addition to dizziness) and suppression of exocrine secretion (for example, dryness of tracheal mucosa due to suppression of tracheal secretion), there are side effect problems such as promotion of bronchial secretion and entanglement of sputum. Also,
In cold syndrome, etc., antihistamines are often used for symptomatic treatment of symptoms such as cough and sputum, as well as runny nose.However, their anticholinergic action extremely suppresses the secretion of water and causes sedation or hypnosis. Negative effects such as a decrease in daily activity due to drowsiness have been recognized. In addition to chemotherapeutic agents, Kampo prescriptions are used for relieving cough and sputum symptoms, and there is no side effect and persistence.
Widely used for temperamental symptoms. However, almost none of them show a rapid action effect, and there is a problem in terms of ingestability or handling, and it cannot be said to be sufficient. The cough / sputum symptom in a moist cough can be released from the unpleasant and difficult breathing symptom by promptly clearing the sputum, and it is often possible to return to the normal level of living activity. There is a long-awaited need for a drug with a high therapeutic effect that can be taken with peace of mind and that alleviates cough / sputum symptoms, rather than a drug that contains a strong narcotic antitussive.

[0005]

[Means for solving the problem] For cough / sputum symptoms, rather than prioritizing antitussiveness, it is possible to relieve cough / sputum symptoms by removing the unpleasant sputum promptly (expectorant). In addition, the inventors of the present invention have conducted intensive studies for the purpose of providing a highly safe pharmaceutical composition with few side effects, and have completed the present invention. That is, the present invention is: 1) a pharmaceutical composition characterized by blending a crude drug having an airway mucus secretion promoting action and an airway mucus viscosity regulator and / or an airway mucosa lubricant, 2) airway mucus viscosity The pharmaceutical composition according to 1) above, wherein the regulator is an airway mucolytic agent or an airway mucus sclerosing agent, 3) the above-mentioned 1), wherein the crude drug having an airway mucus secretion promoting action is at least one of Senega, Kikiyo, Ondi, and Sion.
4. The pharmaceutical composition described in 4), wherein the airway mucolytic agent is N-acetyl L-cysteine, L.
-Methylcysteine, L-ethylcysteine, carbocysteine, serrapeptase, bromelain and at least one of the pharmacologically acceptable salts thereof, the pharmaceutical composition according to the above 2) or 3), 5) an airway mucus sclerosing agent. Is N-acetylneuraminic acid (sodium acenoylate), 6. The pharmaceutical composition according to claim 2 or 3, 6) The airway mucosal lubricant is ambroxol or a pharmacologically acceptable salt thereof, 1). , 3), 4) or 5), and 7) the pharmaceutical composition according to 1), which is a composition for antitussive and expectorant preparation.

The present invention does not focus on the antitussive action, but rather makes the expectoration more secure by adding the action of facilitating the expectoration of sputum and promoting the expectoration of the sputum, and as a result, the composition for promptly calming the cough. Is. The compounded composition contains at least one herbal medicine that has an excellent action on expectoration of sputum and is highly safe (for example, Senega, Kyoukyo, Ondi, Sion, etc.), and one or more mucosal lubricants As an agent and / or airway mucus consistency adjusting agent, one or more kinds of airway mucus hardening agents or airway mucus dissolving agents, preferably three, are blended, depending on the properties of sputum. . Examples of the crude drug having an airway mucus secretion-promoting action that can be used in the composition of the present invention include crude drugs having an airway mucus-secretion promoting action listed in, for example, the Japanese and Chinese medicine encyclopedia (published by a nursery company) or a Chinese medicine dictionary. Therefore, Senega, Kyoukyo, Onji, Sion and the like are preferably used. Among these herbal medicines, those mainly having a peripheral airway mucus secretion promoting action are preferable. Further, here, the crude drug is according to the rules described in the Japanese and Chinese medicine encyclopedia or the Chinese medicine dictionary, but as long as the same effect can be obtained, different parts of the same genus or non-regular parts may be used. These crude drugs are in the form of powder (for example, coarse powder, middle powder, fine powder, fine powder), soft extract (for example, water extract, dilute lower alcohol extract, etc.) and dry extract powder, and they may be used alone or in combination of two or more kinds. It should be mixed. As the blending amount,
It may be appropriately selected depending on the indication, crude drug used or a combination thereof, a combination with other components, and the like.

[0007] Specifically, for example, as Senega, dried Senega or Hirosehaenega roots are usually used, and the compounding amount is 300 to 5000 mg, preferably 1000 in powder as an adult daily dose. ~ 3000 mg. In the case of extract or extract powder, it is 45 to 75 in terms of dry extract.
It may be used so as to obtain a combined extract amount of 0 mg, preferably 150 to 450 mg. For example, as kyokyo, the roots of kyoto of the kyobanaceae family are usually washed with water to remove the fine roots and then used as they are or after cork skin is removed and dried. The daily dose for adults is from 300 to 300 in powder form. 5000
mg, extract or extract powder is 45 to 750 mg, preferably 150 to 450 mg. For example, as Onji, dried roots or root bark of Astragalus membranaceae is usually used, and the adult daily dose is 1000 to 8000 mg as powder,
It is preferably 3000 to 5000 mg. The amount of the extract or extract powder is 100 to 800 mg, preferably 300 to 500 mg. For example, as Zion, dried roots and rhizomes of Asteraceae are usually used, and the adult daily dose is 10
The amount is 00 to 8000 mg, preferably 3000 to 5000 mg. Extract and extract powder 150-1200 mg, preferably 450-750 m
It is g.

Each of these crude drugs has an expectorant action by promoting airway secretion which is characteristic of crude drugs, but there is no definitive difference in their strengths, and rather it is considered that the characteristic drug effect can be brought out by adjusting the compounding amount. . Therefore, these crude drugs are not limited to one kind, and a preferable therapeutic effect is expected by combining two or more kinds. In the production of extracts and extract powders obtained from these crude drugs, water or lower alcohols (methyl alcohol, ethyl alcohol, isopropyl alcohol, etc.), hydrophilic organic solvents (acetone, acetonitrile, etc.), etc. are used as extraction solvents. The dry extract powder can be obtained by pulverizing a dry extract prepared according to a method generally used in the pharmaceutical industry into a desired particle size according to a conventional method. In addition to directly spray-drying the extract extracted from the crude drug, it is also possible to directly obtain the dry extract powder by a wet granulation method or a spray-drying method (spray dry) by adding excipients and additives such as various adsorbents. Good. Moreover, the extracted extract may be filtered and concentrated by a generally adopted method to be used as a soft extract.

Examples of the airway mucus viscosity adjusting agent used in the present invention include airway mucolytic agents and airway mucus hardening agents. This component is a mucolytic action by promoting the secretion of lung surface-active substances, dissolving or lowering the molecular weight of acidic glycoprotein in the mucus component (for example, the action of decreasing the viscosity by cleaving disulfide bonds), or the action of proteolytic enzymes. While mucopolysaccharide degradation, proteolysis, fibrinolysis, etc. decomposes viscous secretions accumulated at the inflammatory site to reduce viscosity and facilitate phlegm production of highly viscous sputum. In the case of very low-viscosity thin sputum, for example, by adding sialic acid, which is a mucus component, for the purpose of appropriately hardening the viscoelasticity of sputum to a level suitable for transportation by airway cilia. Used. Therefore, any one may be appropriately selected and used according to the sputum state (viscosity). The airway mucolytic agent is selected from, for example, cysteine-based preparations such as N-acetyl cysteine, L-ethyl cysteine, L-methyl cysteine, carbocysteine and proteolytic enzyme preparations such as serrapeptase and bromelain.
One kind or two or more kinds may be appropriately combined and used.
The daily dose for adults is determined according to the type and amount of other drugs to be mixed according to known mixing methods.
Carbocysteine, N-acetylcysteine, L-hydrochloride
Usually for methyl cysteine and L-ethyl cysteine hydrochloride
100 to 1500 mg, usually 5 to 200 for proteolytic enzyme preparations
mg, preferably 15-100 mg. The optimum pH of most proteolytic enzyme preparations is on the alkaline side and is inactivated by gastric acid, so it is necessary to take into consideration the formulation such as making it enteric when taken orally. Examples of the airway mucus hardening agent include N-acetylneuraminic acid (aceneulamic acid) and its pharmacologically acceptable salts. The amount used is appropriately changed depending on the symptoms, the combination with other components, etc., but for example, the daily dose of sodium N-acetylneuraminate is 1 to 5 mg. Most of sodium N-acetylneuraminate is decomposed by intestinal bacteria upon oral administration and its intestinal absorption is slight. Therefore, in order to obtain an effective drug, for example, troche, chewable, spray liquid or powder inhalant As a topical 1 to 3 times a day,
Best used when you need the most expectorant.

As the airway mucous membrane lubricant, a drug having a pharmacological action such as an airway mucociliary hyperactivity action is used, and in addition to this action, a drug having a pulmonary surfactant secretion promoting action and an airway fluid secretion promoting action as well. Is preferably used. Specific examples include ambroxol and its pharmacologically acceptable salts. The blending amount may be appropriately changed depending on the symptoms, the combination with other components, and the like. For example, in the case of ambroxol hydrochloride, the adult daily dose is 5 to 60.
mg, preferably 15-45 mg. The pharmacologically acceptable salts include, for example, inorganic acid salts such as hydrochlorides and hydrobromides, organic acid salts such as acetates and tartrates, inorganic base salts such as sodium and potassium, such as ammonium. Any salt such as an organic base salt such as a salt that is safe for the living body and does not impair the original pharmacological action of the drug in the living body may be used, such as solubility and stability in terms of formulation or absorbability. It may be appropriately selected depending on the purpose of administration such as stability.

The combination of the above-mentioned respective components, the amount ratio and the like are appropriately designed according to the indication symptoms and the like, and specific examples thereof include the following formulation design. a) The mild cough without inflammation of the throat, which is often seen in the common cold, and when applied to the condition in which the cough disappears when the sputum is cut off, the antitussive / expectorant action of Senega and the persistent action of Zion. Good expectorant action (enhancing respiratory secretions and making sputum easier to cut off)
, Which is designed to be combined with an airway mucolytic agent such as L-ethylcysteine hydrochloride, which is expected to prevent phlegm viscousization and also have a drainage effect. b) When watery sputum is entangled in the throat and is accompanied by inflammation of the throat, moderate airway secretion by a herbal mixture component (eg, kyoto, ondi, sion), which also has an anti-inflammatory effect, can be used for proper respiratory secretion. By mixing an airway mucus hardening agent such as sodium, the sputum is made to have a certain degree of hardness (viscosity) to facilitate sputum production. c) In the case of stubborn symptoms of phlegm in the latter stage of inflammation, successful moderate airway secretion due to herbal mixture components (Senega, Kyoukyo, Ondi) and airway ciliary movement with airway mucosal lubricant such as ambroxol hydrochloride The increased sputum causes the solidified (highly viscous) sputum to be discharged as it is. d) In the case of low-viscosity sputum with mild cough (a condition in which the throat is tingling and sputum is entangled one after another), the ratio of sialic acid and fucose, which are the constituents of sputum, was normalized. The action of carbocysteine and serrapeptase causes the sputum to have an appropriate hardness, and in addition to the antitussive and expectorant actions of Senega, Sion, which has a superior expectorant action, is added to enhance the airway ciliary movement and enhance the action of sputum. Combines ambroxol hydrochloride, which contributes to excretion, to achieve good expectorant action.

E) In the case of stubborn tangled sputum without cough, the main focus is on the action of stubbornly clinging sputum to moderately enhance airway secretion (expectorant action by Zion, Onji, and Kyoukyo), and sputum removal. To reduce elasticity by improving airway mucus-dissolving agent (L-ethylcysteine hydrochloride +
Bromelain, etc.) is added, and the action of an airway mucosal lubricant such as ambroxol hydrochloride facilitates sputum. f) For symptoms in which watery sputum is frequently entangled in the trachea and makes it difficult to breathe and sputum is not performed successfully, it is better to harden the sputum to a hardness that facilitates sputum rather than promoting airway secretion. It may be more effective. In this case, as a crude drug, Ondi, which has a mild and safe antitussive and expectorant action, and sion, which has a therapeutic effect on expectorant rather than antitussive, are mixed, and sputum watery sputum is treated with an airway mucus-hardening agent such as sodium asenoiramate. It hardens to an easy hardness, and it further successfully causes sputum due to the airway ciliary motility enhancing action of an airway mucosal lubricant such as ambroxol hydrochloride. g) Regardless of the presence or absence of a cough, in the case of a formulation which is expected to have a local action and a systemic action in order to promote sputum more smoothly, a locally applied crude drug such as Senega having a reflex airway secretion action due to a mucous membrane stimulating action And a crude drug that has a persistent airway secretagogue action such as Zion are combined and combined to facilitate sputum due to the action of an airway mucosal lubricant such as ambroxol hydrochloride, and depending on the nature (viscosity) of sputum. For low-viscosity sputum, 1 or 2 or more airway mucus-hardening agents such as sodium asenoylamate are added, and for high-viscosity sputum, 1 or 2 or more airway mucus-dissolving agents such as carbocysteine are added.

The composition of the present invention comprises oral solid preparations such as tablets, powders, fine granules, granules, capsules, suspensions, troches and chewable preparations, and elixirs and syrups (including dry syrup). It can be administered in the form of a liquid preparation or the like. In addition, when unsuitable for oral administration or when faster and more reliable drug efficacy is required by selecting local administration, conventional liquid injection,
Mist spray and nebulizer injection method, and powder inhaler using spin-heller and disc-heller (dry powder devi
ce; DPD) and metered dose inhaler;
It is administered by a method such as MDI). In these cases, convenience,
It is selected in consideration of certainty and efficiency. The dosage and administration dose can be adjusted appropriately depending on the formulation form. That is, the daily dosage may be taken as an oral solid preparation such as a tablet or an oral solution in one to several divided doses.
In addition, for example, in the case of a drug product such as syrup, troche, chewable tablet, etc., which has a local action and a systemic action by oral administration,
2 to 1/10 may be blended and taken as a single dose, in which case the total dose may not be less than the daily dose. On the contrary, if the dose is not unreasonable in view of the dosage form, an amount corresponding to the daily dose may be added as a single dose. Also,
In the case of liquid injection, mist spray, nebulizer injection method, powder inhalation method, etc. for topical application, the dose may be adjusted to 1/10 to 1/100 of the oral dose for internal use.

In preparing the preparation, diluents and excipients such as fillers, fillers, binders, disintegrants, surfactants, lubricants, coating agents and sustained-release agents which are usually used are used. be able to. In addition, solubilizers, buffers, preservatives, solubilizers, isotonic agents, emulsifiers, suspending agents, dispersants, thickeners, gelling agents, curing agents, absorbents, if necessary.
Adhesives, elastic agents, plasticizers, adsorbents, fragrances, coloring agents, flavoring agents, antioxidants, moisturizers, light-shielding agents, brighteners, antistatic agents and the like can be used. More specifically, as an excipient, lactose, corn starch, mannitol, D-sorbitol, crystalline cellulose, erythritol, sucrose, and the like, and as a binder, hydroxypropyl cellulose (H
PC-L), hydroxypropylmethylcellulose, polyvinylpyrrolidone, methylcellulose, pregelatinized starch, etc., carmellose calcium, croscarmellose sodium, cross-linked polyvinylpyrrolidone, etc. as disintegrants, magnesium stearate, talc etc. as lubricants. is there. Examples of the fragrance include flavors such as 1-menthol, vanillin, lemon oil, cinnamon oil, and peppermint oil, and aromatic oils, and the adsorbent may contain synthetic aluminum silicate, light anhydrous silicic acid, and the like. Further, a coating preparation can be prepared by using a coating agent which is usually used such as hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose and polyvinylpyrrolidone. In addition, if necessary, a sweetener can be used particularly in lozenges, syrups, chewable agents and the like. That is, mannitol (mannitol), glucose (glucose), maltose (maltose), starch syrup, malt extract, maltitol,
Examples include sorbitol, sucrose, brown sugar, fructose, lactose, honey, xylitol, sweet tea, saccharin, aspartyl phenylalanine ester, and other oligosaccharides such as maltooligosaccharides, maltosyl sucrose, reduced isomaltulose, and raffinose. To be The formulation using these can be carried out by any of the methods known in the art, conventional methods and conventional methods depending on the formulation form.

Powder and granular preparations such as powders, fine granules and granules (including metered dose inhaler (MDI) and powder inhaler (DPD))
The desired formulation can be prepared in consideration of properties such as splattering property and adhesiveness. For example, powder bulk, splattering property, adhesive property, hygroscopicity, electrostatic property, wettability, solubility, etc. It is preferable to prepare a pharmaceutical preparation in consideration of the physical properties, particle size (particle diameter), surface area, shape and other properties. Specifically, it is said that in the powder inhalation method, it is necessary to pay attention to the particle size of the drug component in order to make the drug efficiently reach the sputum affected area,
The most suitable particle size is 0.5 to 5.0 μm. Further, it is preferable to prepare it in consideration of facilitation of handling and prevention of moisture absorption, decomposition, deterioration, discoloration and the like. As a pulverizing method for preparing the powder, a dry pulverizing method, a wet pulverizing method, a low temperature pulverizing method,
It can be appropriately selected by a conventionally used method such as a jet pulverizing method, a batch pulverizing method, a continuous open circuit pulverizing method, a continuous closed circuit pulverizing method, or a combination thereof depending on the purpose.

[0016]

EXAMPLES Some preferred examples of the formulation of the present invention will be described below, but the present invention is not limited thereto. In addition, in the following formulation examples, unless otherwise specified, the blending amount of each component represents an adult daily dose, and the formulation is carried out according to the above-mentioned conventional method. [Formulation Example 1] Senega dry extract 450 mg (raw drug equivalent 3,000 mg) Zion dry extract 450 mg (raw drug equivalent 3,000 mg) L-ethyl cysteine hydrochloride (enteric) 250 mg According to the above, it is prepared as an oral preparation such as tablets, powders, granules or capsules. In this blending, in order to prevent the decomposition of L-ethylcysteine hydrochloride by gastric acid, it is preliminarily made into enteric coated granules and blended. [Formulation Example 2] Onji dried extract 300 mg (active ingredient equivalent 2,000 mg) Kyoukyo dried extract 150 mg (active ingredient equivalent 1,000 mg) Sion dried extract 300 mg (active ingredient equivalent 2,000 mg) Sodium acenoylate 4 mg Above The compounded composition is preferably in the form of a preparation which is as easy to apply topically as possible. For example, it is desirable to prepare a solid preparation such as chewable troche or troche or a syrup.

[Formulation Example 3] Dry extract of Senega 500 mg (amount of crude drug equivalent: 3,333 mg) Dried extract of kyoto: 500 mg (amount of crude drug equivalent: 3,333 mg) Dried extract of Onji (500 mg, equivalent amount of a crude drug 5,000 mg) Ambroki hydrochloride Sol 45 mg The above-prepared composition was added to tablets, powders, granules, capsules,
Alternatively, it is prepared as a liquid preparation. [Formulation Example 4] Dry extract of Senega 150 mg (amount of crude drug equivalent 1,000 mg) Dried extract of Zion 300 mg (amount of crude drug equivalent 2,000 mg) Carbocysteine 300 mg Serrapeptase 10 mg Ambroxol hydrochloride 30 mg Prepare as tablets, powders, granules, and capsules. [Formulation Example 5] Dried sion extract 750 mg (5,000 mg equivalent of the original drug) Onji dried extract 100 mg (1,000 mg equivalent of the original drug) Dried kyokyo extract 450 mg (3,000 mg equivalent of the original drug) L-ethylcystine hydrochloride ( Enteric-coated) 200 mg Bromelain (enteric-coated) 40 mg (32,000 bromelain units) Ambroxol hydrochloride 50 mg The above-mentioned compounded composition is prepared as a tablet, a fine granule, a granule or a capsule. In this formulation, in order to prevent decomposition by gastric acid due to oral administration of L-ethylcysteine hydrochloride and bromelain, enteric-coated granules are preliminarily prepared and blended. As the coating agent, conventionally used hydroxypropylmethylcellulose phthalate 200731, purified shellac, Macrogol 6000 and the like are preferably used.

[Formulation Example 6] Dried extract of Ondi (30 mg, 300 mg of crude drug equivalent) Dried extract of Zion, 45 mg (300 mg of crude drug equivalent) Sodium acenoylate 2 mg Ambroxol hydrochloride 5 mg Is used in a topical dosage form by nebulizer inhalation or powder inhalation. In this formulation, it is sprayed and sprayed directly on the trunk, so if necessary, a flavoring agent (sweetener)
May be added to the product to improve the feeling of ingestion. Since this formulation is to be sprayed / sprayed directly onto the affected area, a flavoring agent (sweetening agent) may be added if necessary to provide the product in a form in which the feeling of ingestion is improved. In this formulation form, the above-mentioned compounding amount is 1 to 3 per day.
Since it may be taken as a single dose or in divided doses, it may be taken in consideration of the dosage form as appropriate. [Compound Example 7] Senega dried extract 150 mg (amount of crude drug equivalent of 1,000 mg) Dried kyoto extract 100 mg (amount of crude drug equivalent of 1,000 mg) Onji dried extract 100 mg (amount of crude drug equivalent of 666 mg) Sion dried extract 150 mg ( Raw drug equivalent amount 1,000 mg) Carbocysteine 30 mg Ambroxol hydrochloride 10 mg It is appropriate to formulate the above-mentioned component combination composition into a troche or a chewable tablet. In this case, it can be prepared by appropriately adding a corrigent (sweetening agent) or the like in consideration of ingestability. It is appropriate that the lozenge is formed into 1 to 2 tablets, 1 to 3 times a day, and the chewable tablet is 1 to 2 tablets, 1 to 3 times a day.

[Formulation Example 8] A lozenge or a chewable tablet is prepared by adding 4 mg of sodium acenoylate instead of 30 mg of carbocysteine among the above-mentioned components up to ambroxol hydrochloride. [Formulation Example 9] Senega flow extract 1 ml (amount of crude drug equivalent: 1,000 mg) Ambroxol hydrochloride 30 mg The above-mentioned component combination composition is used as a syrup or a liquid agent once a day.
It is suitable to prepare a formulation to be taken 3 times. It can also be prepared by appropriately adding a flavoring agent (sweetening agent) or the like in consideration of ingestability.

[Formulation Example 1] Chewable tablets I-grain Senega dry extract 150 mg Kyoukyo dry extract 100 mg Onji dry extract 100 mg Zion dry extract 150 mg Crystalline cellulose 500 mg Corn starch 540 mg Mannitol 3321.9 mg HPC-L 256 mg Aspartame 5 0.1mg After uniform mixing, granulate according to the usual method to make uniform granules. II particles Carbocysteine 30 mg Ambroxol hydrochloride 10 mg Crystalline cellulose 150 mg Corn starch 300 mg Mannitol 2417 mg HPC-L 90 mg Aspartame 3 mg After uniform mixing, granulate according to a conventional method to obtain uniform granules. I granules 5123 mg II granules 3000 mg Corn starch 252 mg Magnesium stearate 25 mg After uniform mixing, the tablets were compressed according to a conventional method to give 1 tablet 1400 mg.
Of tablets.

[Formulation Example 2] The composition of the chewable tablets II grains was changed as follows, and in the same manner as in Preparation Example 1, 1400 mg of chewable tablets was prepared. Sodium acenolymate 4 mg Ambroxol hydrochloride 10 mg Crystalline cellulose 150 mg Corn starch 300 mg Mannitol 2443 mg HPC-L 90 mg Aspartame 3 mg

[Effect] The composition of the present invention quickly and cleanly removes sputum in cough / sputum symptoms, particularly in cough / sputum symptoms in a wet cough, and releases the discomfort caused thereby.
It is a safe and highly effective combination drug that cleans and relieves cough symptoms without the use of strong antitussives.

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Claims (7)

[Claims] 1. A pharmaceutical composition comprising a crude drug having an airway mucus secretion promoting action, an airway mucus viscosity regulator and / or an airway mucosal lubricant. 2. The pharmaceutical composition according to claim 1, wherein the airway mucus viscosity adjusting agent is an airway mucolytic agent or an airway mucus hardening agent. 3. The pharmaceutical composition according to claim 1, wherein the crude drug having an action of promoting mucus secretion in the respiratory tract is at least one of Senega, Kikyo, Ondi, and Sion. 4. An airway mucolytic agent is N-acetyl L-cysteine, L-methyl cysteine, L-ethyl cysteine,
The pharmaceutical composition according to claim 2 or 3, which is at least one of carbocysteine, serrapeptase, bromelain and a pharmacologically acceptable salt thereof. 5. The pharmaceutical composition according to claim 2 or 3, wherein the airway mucous hardening agent is N-acetylneuraminic acid (sodium acenoylate). 6. The airway mucosal lubricant is ambroxol or a pharmacologically acceptable salt thereof, 1, 3, 4
Or the pharmaceutical composition according to 5. 7. The pharmaceutical composition according to claim 1, which is an antitussive and expectorant composition.