JPH11199498A - Pharmaceutical preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a pharmaceutical preparation which has high safety, excellent pharmaceutical stability and bad breath reducing effect. SOLUTION: This pharmaceutical preparation includes an active ingredient against gastrointestinal malady and a tea powder or an extract extracted from tea. The active ingredient is selected from antacids, mucosa repairing agents, stomachics, drugs for controlling intestinal function or digestive agents. The tea powder or extract extracted from tea used in this invention is a powder, an extraction solution or an extract obtained by various methods from arbitrary portions, e.g. leaves, stems or leaf buds of various teas such as green tea, powdered green tea, oolong tea and black tea, for example, a green tea powder, a powdered green tea (minute powder), an oolong tea extract or a black tea extract is illustrated. On these matters, goods on the market are used or it can be prepared by usual methods. The green tea powder or the powdered green tea is favorable. It is possible to be blended in an amount of 0.01-300 mg at a daily dosage and to be increased and decreased due to the dosage form and the unit dose.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a pharmaceutical preparation containing a tea powder or a tea extract.

[0002]

2. Description of the Related Art In the case of gastrointestinal inflammation or indigestion caused by overeating, there is a problem that undigested substances staying in the gastrointestinal tract generate a bad smell and give discomfort. In conventional gastrointestinal drugs, efforts have been made to focus on improving gastrointestinal mucosal repair and digestion promoting effects. Therefore, as the inflammation of the gastric mucosa is repaired, retentate is sent out, and digestion proceeds,
The only way to avoid malodor over time was to use a passive method based on eliminating the cause of the malodor. Therefore, the conventional method using a gastrointestinal drug was not effective against bad odor caused by gastrointestinal disorders or bad breath caused by gastrointestinal dysfunction due to stress. On the other hand, medicines for gastrointestinal diseases are improved by adding sweeteners, fresheners, and fragrances to reduce discomfort such as bitterness and smell when taking the medicine. Was not considered at all.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide a pharmaceutical preparation excellent in the effect of reducing bad breath, which is high in safety and excellent in pharmaceutical stability.

[0004]

Means for Solving the Problems The present inventors have conducted intensive studies in order to solve the above-mentioned problems, and as a result, by adding tea powder or tea extract to a pharmaceutical preparation, the preparation has excellent stability. It has been found that a safe formulation excellent in the effect of preventing bad breath can be obtained. It has been conventionally known that tea powder and tea extract have a bad breath suppressing effect, but it is known that when combined with a drug having an effect on gastrointestinal diseases, a sufficient bad breath suppressing effect is exhibited. Not been. The strength of the bad breath suppressing effect depends on the dosage form and the formulation technique, as well as the selection of the bad breath suppressing agent. It is more preferable to mix tea powder or tea extract as a solid preparation.

[0005] In addition, digestive agents, mucosal repair agents, antacids, and stomachic agents, which are commonly used for gastrointestinal diseases, have weak halitosis-suppressing activity. Have been found to be enhanced. Even more surprisingly, it has been found that the incorporation of tea powder or tea extract into a solid formulation improves formulation properties and enhances stability of digestive and mucosal repair agents and the like. Digestive agents and mucosal repair agents are generally components that tend to cause problems such as a decrease in potency at the time of formulation processing and stability after formulation. In particular, formulations formulated with antacids are more problematic in terms of overall formulation development because their stability is more likely to decrease, but formulations containing tea powder or tea extract increase the stability of digestive and mucosal repair agents Was found.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The tea powder or tea extract used in the present invention is obtained from various parts such as green tea, matcha tea, oolong tea, black tea leaves, stems and buds by various methods. , Powder, extract, extract, and the like, for example, green tea powder, matcha (fine powder), oolong tea extract, black tea extract and the like. These are commercially available or
It can also be prepared by a usual method. Green tea powder or matcha is preferred. The daily dose may be 0.01 mg to 300 mg, and the dose may be appropriately adjusted depending on the dosage form, unit dose, and the like.

[0007] The pharmaceutical preparation of the present invention suppresses gastrointestinal disorders and accompanying bad breath by blending an active ingredient such as an antacid, a mucosal repair agent, an intestinal regulant, a stomachic, a digestive agent and tea powder or a tea extract. Or can be removed. Examples of the active ingredient used in the present invention include dried aluminum hydroxide gel, magnesium aluminate silicate, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, sodium hydrogen carbonate, magnesium carbonate, magnesium hydroxide, and water. Antacids such as magnesium alumina oxide, cimetidine, ranitidine, famotidine and the like can be mentioned. Further, sodium azulene sulfonate, aldioxa, glycyrrhizic acid and salts thereof and licorice extract, L-glutamine, copper chlorophyllin potassium, histidine hydrochloride, etc. ,
Examples include stomach medicines such as oak, calyx, assembly, rhubarb and carrot, and digestive agents such as starch digestive enzyme, protein digestive enzyme, lipolytic enzyme, fibrinolytic enzyme, ursodesoxycholic acid, bile powder, and bile extract. In addition, an active ingredient such as an analgesic and antispasmodic such as scopolamine hydrobromide, methyl scopolamine bromide, and papaverine hydrochloride, and an antidiarrheal such as berberine chloride, guaiacol, tannic acid, and precipitated calcium carbonate can be added. The amounts of these active ingredients are appropriately compounded in the usual dose. The pharmaceutical preparations of the present invention can be administered orally in various dosage forms: tablets, chewables, pills, powders, fine granules,
It can be prepared and used as solid preparations such as granules and capsules, and liquid preparations such as aqueous solutions, oily solutions, suspensions, emulsions, syrups, etc., but solid preparations are preferred due to the effect of tea powder. It is. Each of the above-mentioned preparations is prepared by a conventional method, but is prepared by using various additives as necessary.

The additives used include, for example, lactose, sucrose, corn starch, crystalline cellulose,
Mannitol, excipients such as calcium carbonate, hydroxypropylmethylcellulose, binders such as hydroxypropylcellulose, talc, magnesium stearate, lubricants such as calcium stearate, carboxymethylcellulose, disintegrants such as low-substituted hydroxypropylcellulose, Essential oil components such as l-menthol, peppermint oil and lemon oil, fragrances such as mint oil, chlorophyll and the like. Addition of chlorophyll is preferable because the effect of suppressing bad breath increases, and the addition of an essential oil component increases the effect on stomachic. In addition, other additives commonly used in the production of solid preparations and liquid preparations such as solubilizers, stabilizers, emulsifiers, diluents, preservatives, sweeteners, and flavoring agents can be used. Hereinafter, specific examples of the pharmaceutical preparation of the present invention will be described, but the present invention is not limited thereto.

[0009]

EXAMPLES Preparations were prepared comprising the components shown in Tables 1 and 2 below. Example 1-5

[Table 1] Unit: (mg)

Reference Example 1-6

[Table 2] Unit: (mg) The production method is shown below.

Example 1 Xylitol, mannitol, hydroxypropylcellulose, crystalline cellulose, magnesium carbonate, precipitated calcium carbonate, and synthetic hydrotalcite are mixed, granulated, dried and crushed by a conventional method to obtain a powder. Green tea powder is added to the resulting powder and mixed. Further, an appropriate amount of magnesium stearate is added and mixed to obtain a mixed powder for tableting. Chewable tablets and tablets were obtained. Thereafter, the mixed powder for tableting was tableted to obtain chewable tablets (diameter: 18 mm, hole diameter: 6 mm) or tablets. In order to compare the effects, chewable preparations or tablets obtained by removing the green tea powder from the formulation of Example 1 as Reference Example 1 were obtained in the same manner as in Example 1. Tablets or chewables having the component contents shown in Tables 1 and 2 per tablet were obtained.

Example 2 Xylitol, mannitol, hydroxypropylcellulose and microcrystalline cellulose were mixed and granulated by a conventional method.
Dry and crush to obtain powder. Add green tea powder, biodiastase, lipase and prozyme to the resulting powder and mix. Further, an appropriate amount of magnesium stearate is added and mixed to obtain a mixed powder for tableting. Thereafter, the mixed powder for tableting was tableted to obtain chewable tablets (diameter: 18 mm, hole diameter: 6 mm) or tablets. In order to compare the effects, chewable preparations or tablets obtained by removing the green tea powder from the formulation of Example 2 as Reference Example 2 were obtained in the same manner as in Example 2. Tablets or chewables having the component contents shown in Tables 1 and 2 per tablet were obtained.

Example 3 Xylitol, mannitol, hydroxypropylcellulose, and crystalline cellulose were mixed and granulated by a conventional method.
Dry and crush to obtain powder. Green tea powder, aldioxa and L-glutamine are added to the resulting powder and mixed. Further, an appropriate amount of magnesium stearate is added and mixed to obtain a mixed powder for tableting. Thereafter, the mixed powder for tableting is tableted to obtain chewable tablets (diameter 18 mm, hole diameter 6 mm) or tablets.
In order to compare the effects, a chewable preparation or tablet obtained by removing the green tea powder from the formulation of Example 3 as Reference Example 3 was obtained in the same manner as in Example 3. Tablets or chewables having the component contents shown in Tables 1 and 2 per tablet were obtained.

Example 4 Xylitol, mannitol, hydroxypropylcellulose and microcrystalline cellulose were mixed and granulated by a conventional method.
Dry and crush to obtain powder. Add green tea powder, carrot powder and calyx powder to the resulting powder and mix. Further, an appropriate amount of magnesium stearate is added and mixed to obtain a mixed powder for tableting. Thereafter, the mixed powder for tableting is tableted to obtain chewable tablets (diameter 18 mm, hole diameter 6 mm) or tablets. In order to compare the effects, a chewable preparation or tablet obtained by removing the green tea powder from the formulation of Example 1 as Reference Example 4 was obtained in the same manner as in Example 1. In order to compare the effects, a chewable preparation or tablet obtained by removing the green tea powder from the formulation of Example 4 as Reference Example 4 was obtained in the same manner as in Example 4. Tablets or chewables having the component contents shown in Tables 1 and 2 per tablet were obtained.

Example 5 Xylitol, mannitol, hydroxypropylcellulose, crystalline cellulose, magnesium carbonate, precipitated calcium carbonate, synthetic hydrotalcite Granulated by a conventional method.
Dry and crush to obtain powder. Green tea powder and biodustase, lipase, prozyme, aldioxa,
Add L-glutamine and mix. Further, an appropriate amount of magnesium stearate is added and mixed to obtain a mixed powder for tableting. Thereafter, the mixed powder for tableting is tableted to obtain chewable tablets (diameter 18 mm, hole diameter 6 mm) or tablets. In order to compare the effects, a chewable preparation or tablet obtained by removing the green tea powder from the formulation of Example 5 as Reference Example 5 was obtained in the same manner as in Example 5. Tablets or chewables having the component contents shown in Tables 1 and 2 per tablet were obtained.

Test Example 1 Improvement of Mixability In Example 1 and Reference Example 1, xylitol 525 was used.
g, mannitol 220 g or 250 g, hydroxypropyl cellulose 50 g, crystalline cellulose 25 g, magnesium carbonate 150 g, precipitated calcium carbonate 200
g and 100 g of synthetic hydrotalcite are mixed, granulated, dried and crushed by a conventional method to produce a powder. Thus obtained powder of Example 1, 30 g of green tea powder and aldioxa 10
g or the powder of Reference Example 1 and 10 g of aldioxa,
It is charged into a V-type mixer (V3 manufactured by Showa Kogyo) and mixed at a rotation speed of 14 rpm. After mixing, after 5, 10, 15, 30, 45, and 60 minutes from the start of mixing, 150 to 200 mg of mixed powder samples were collected from five different locations in the mixer, and the mixed powder per unit mixed powder was collected. The amount of allantoin (component in aldioxa) is determined by liquid high performance chromatography. From the quantitative value of allantoin, the variation value (standard deviation of 5 samples / 5 average value of samples) of the samples collected at five different places was calculated, and the degree of mixing was evaluated. Table 3 shows the results. Good uniformity was obtained from the early stage of mixing by blending the tea powder. At the time of preparation of mixed granules for tableting,
Mixing of the fine powder is difficult and causes uneven distribution. If only the granulated material and the aldioxa are mixed, it can be mixed in a short time,
Although it is difficult to obtain a uniform mixture, when the green tea powder is added and mixed at the same time, the component uniformity of the mixed powder is improved.

Table 3 Changes in the degree of mixing

[Table 3]

Test Example 2 Improvement of Tableting Characteristics The mixed granules were subjected to a tableting machine (HT-E5-S manufactured by Hata Iron Works) at a rotation speed of 15 to 20 rpm, a tableting pressure of 4 to 5 t / punch, and both R surfaces. , A chewable agent having a diameter of 18 mm and a hole diameter of 6 mm was continuously tableted for 8 hours. When the appearance of the chewables of Examples 1 to 5 and Reference Examples 1 to 5 was visually observed, in Reference Example 1, tableting troubles such as binding, capping, and sticking were observed from around 30 minutes of tableting time. In Example 1, no tableting trouble was observed. Example 1
The mixed powders Nos. 1 to 5 had better bonding strength than Reference Examples 1 to 5 and showed high tablet hardness.

Test Example 3 Improvement of Tablet Disintegration A disintegration test was performed according to the 12th edition of the Japanese Pharmacopoeia. Example 1
In Nos. To 5, all tablets disintegrated within the prescribed 15 to 20 minutes. On the other hand, in Reference Examples 1 to 5, the variation in the disintegration time is large, 25 to 40 minutes, which is the specified value of 30.
In some cases, it took more than a minute.

Test Example 4 Deodorizing effect of malodorous substances 1 ml of methyl mercaptan and 50 ml of water were put into a 200 ml suction bottle as malodorous solution and stirred for 1 minute. The gas in the methyl mercaptan suction bottle is led to the detector tube, and the methyl mercaptan concentration is measured and used as a control value. In another suction bottle, 1 ml of methyl mercaptan and Examples 1 to 5, Reference Example 1
チ ュ 5 chewable tablets were pulverized to obtain 4
Add 00 mg and 50 ml of water, stir for 1 minute, guide the gas in the suction bottle to the detector tube, and measure the methyl mercaptan concentration. Further, in order to confirm the deodorizing effect of the green tea powder, Reference Example 6, which was produced in the same manner as in Example 1 except that magnesium carbonate, precipitated calcium carbonate and synthetic hydrotalcite were removed, was obtained. The mercaptan concentration was measured. The difference between the control value and the measured value of the sample / the control value was taken as the deodorizing rate (%), and the deodorizing rate was compared to evaluate the deodorizing effect of the green tea powder. The results are shown in Table 4. . Table 4 Deodorizing effects

[Table 4]

Test Example 5 Improvement in Stability The chewable ring tablet of Example 5 and Reference Example 5 was
Sealed packaging with aluminum laminated film in units of 0 tablets, 4
Stored in a 0 ° C thermostat. The package was taken out over time, and the tablets were crushed for analysis. The effect of green tea powder on the stability of the blended aldioxa and digestive enzymes was evaluated. Starch saccharification, protein digestion, and fat digestion were quantified to evaluate the stability of the digestive enzymes biodiastase, lipase, and prozyme aldiaxa, and allantoin content was quantified as the evaluation of the stability of aldioxa.
The residual rate (residual rate (%) = quantitative value / initial value) was determined from the quantitative value and the initial value after a storage period of one month, two months, three months, and six months. The formulation of the present invention was shown to have high digestive enzyme activity and high stability of allantoin. Table 5 shows the results.

Table 5 Stability test

[Table 5] Note: (-) in the table indicates that there is no data.

Test Example 6 Salivary Secretion-Promoting Effect The effect brought about by mastication during administration was examined. With the mouth still, the saliva accumulated in the mouth for 5 minutes was discharged, and the weight of the saliva was measured to determine the normal secretion amount. Subsequently, the chewable tablets of Examples 1, 2, and 5 were chewed in the mouth for 30 seconds, held in the mouth for further 30 seconds, and then all were exhaled, and the weight of saliva secreted when the chewed mouth was taken was measured. Also,
The weight of saliva exhaled in the still state three times every 5 minutes from the first ejection was measured, and this was used as the trend of the weight of saliva secreted after taking the saliva. The test was performed by five volunteers. In addition, a tablet obtained by tableting only lactose was used as a placebo. Table 6 shows the ratio between (the amount of saliva secreted after ingestion) and (the amount of saliva secreted under normal conditions). All the examples promoted salivary secretion, and were particularly remarkable in Example 5 which is a composite formulation.
Since saliva has amylase activity, such an increase in saliva secretion is more preferable because of an increase in digestive action. Table 6 Time change of (salivary secretion after taking / salivary secretion at normal time)

Embedded image

Test Example 7 Action on Antacid by Chewing The tablet of Example 5 was discharged together with saliva after chewing, and the action of saliva on the antacid was observed by modified Fuchs' method. Chew the tablet until it becomes fine, hold it in the mouth for 5 minutes, and then discharge it. Then, every 5 minutes, dilute the whole liquid exhaled saliva in the mouth with water to 45 ml, and add 1N hydrochloric acid TS at the start of measurement. It was added at a rate of 2 ml / min. The pH curve immediately after the addition of 5 ml of 1N hydrochloric acid test solution was observed. Example 5 as control
Was crushed and tested similarly. In the case of mastication mixed with saliva, a marked improvement in antacid action was observed 10 minutes after the start of measurement.

Test Example 8 Improvement of Lipophilicity by Chewing The tablet of Example 5 was chewed, held in the mouth for 5 minutes, and then all was discharged together with saliva. 10 ml of the discharged chewing mixture and 5 ml of olive oil are placed in a stoppered centrifuge tube having a capacity of 20 ml and shaken for 10 minutes. After standing, the content liquid immediately separated into an aqueous layer and an emulsion layer. After standing for 10 minutes, only the emulsion layer was separated, and a 1: 1 mixed powder of the hydrophilic colorant Blue No. 1 and the lipophilic colorant Sudan 3 was added and shaken.
As a control, the same operation was performed using purified water in place of the chewing mixture. In the case of the chewing mixture, the emulsion was blue and O / W type, whereas the control emulsion was a mixture of blue and red. By chewing the tablet of Example 9, the tablet was emulsified in a short time, the lipophilicity of the chewing mixture was increased, and it was shown that the tablet had an effect of promoting fat digestion in the digestive tract.

Test Example 9 Breath Removal Effect The breath breath removal effect upon taking the breath was sampled by six volunteers according to the following procedure and collected using an odor sensor (XP-329, manufactured by Kosmo Electric Co., Ltd.). The odor concentration in the exhaled breath was measured. After rinsing with 50 ml of water, expiration is discharged into a 2 L plastic bag.
After chewing the chewable tablet of Example 5 for 1 minute, all is spit out and rinsed with 50 ml of water. Immediately after that 2L
Discharge into a plastic bag of capacity. After rinsing with 50 ml of water, expiration is discharged into a 2 L vinyl bag. After chewing 2g of raw grated garlic for 1 minute, spit out everything, 50m
Wash with 1 l of water. Immediately after that, the expired air is discharged into a 2 L plastic bag. After rinsing with 50 ml of water, expiration is discharged into a 2 L vinyl bag. After chewing one chewable tablet and 2 g of grated garlic at the same time for 1 minute, all are spit out and rinsed with 50 ml of water. 2 liters of breath immediately after mouthwash
Discharge to capacity plastic bag. From the measured values of these breath samples, the residual ratio of odor was determined by the following equation.

## EQU1 ## Residual rate (%) = ｛(smell concentration in breath after chewing chewing gum and garlic−odor concentration in breath after chewing chewing gum)
/ Odor concentration in breath after chewing garlic｝ x100 =
[{(−) − (−)} / (−)] × 100 By taking the chewable tablet of Example 5, the residual ratio of the odor immediately after ingestion of garlic was 31.6%, and about 70% of the odor was reduced. It was found that it was removed.

Claims (5)

[Claims] 1. A pharmaceutical preparation containing tea powder. 2. A pharmaceutical preparation comprising a pharmaceutically acceptable active ingredient and tea powder or tea extract. 3. The pharmaceutical preparation according to claim 1, wherein the pharmaceutical preparation is a solid preparation. 4. The pharmaceutical preparation according to claim 2, wherein the pharmaceutically acceptable active ingredient is an active ingredient for gastrointestinal diseases. 5. The pharmaceutical preparation according to claim 2, wherein the active ingredient for gastrointestinal diseases is selected from the group consisting of an antacid, a mucosal repair agent, a stomachic, an intestinal medicine and a digestive agent.