JPH08208465A - Therapeutic agent of cold - Google Patents

Abstract

PURPOSE: To provide a cold treating agent having increased anti-inflammatory action, analgesic action and antipyretic action, exhibiting antiulcer action and capable of suppressing gastrointestinal disorder. CONSTITUTION: This cold treating agent contains ibuprofen and SAIKO- KEISHITO extract as active components. The amount of the SAIKO-KEISHITO is preferably 5-7 pts.wt. in dry weight based on 1 pt.wt. of ibuprofen. A SAIKO- KEIHITO derived from a mixed herb drug composed of 5.0 pts.wt. of SAIKO (root of Bupleurum falcatum), 4.0 pts.wt. of HANGE (rhizome of Pinellia ternata), 3.0 pts.wt. of KEIHI (bark of Cinnamomum cassia), 3.0 pts.wt. of SHAKUYAKU (root of Paeonia albiflora), 2.0 pts.wt. of OUGON (root of Scutellaria baicalensis), 2.0 pts.wt. of TAISOU (fruit of Zizyphus vulgaris), 2.0 pts.wt. of NINJIN (rhizome of Panax ginseng), 2.0 pts.wt. of KANZOU (root of Glycyrrhiza glabra) and 1.0 pt.wt. of SHOUKYOU (rhizome of Zingiber officinale) is suitable for the cold treating agent.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a remedy for colds. More specifically, it relates to a remedy for colds containing ibuprofen and saikokeishito extract as active ingredients.

[0002]

BACKGROUND OF THE INVENTION Ibuprofen has anti-inflammatory, analgesic and antipyretic effects and is used for inflammatory and painful diseases such as common cold, but when orally administered, it causes gastrointestinal disorders as a side effect. It has been known.

As a method for alleviating gastrointestinal disorders caused by oral administration of ibuprofen, suppositories or [applied pharmacology, 24
Vol. 549-560 (1982)], ibuprofen with a combination of acetaminophen and a magnesium-based antacid (Japanese Patent Laid-Open No. 5-1
No. 48139) is known, but not always satisfactory results have been obtained.

Ibuprofen [chemical name; 2- (4-isobutylphenyl) propionic acid] contains R (-) and S
There are enantiomers of (+) (hereinafter referred to as R-form and S-form, respectively), but the active substance is known to be the S-form. Further, ibuprofen is usually administered (taken) in a racemic form, but after administration, the R form is converted into the S form in the body [Br.J.Clin.Pharmac., Vol. 19, pp. 669-674, ( 198
Five)].

Saiko-keishi-to is gastroenteritis accompanied by abdominal pain, low-grade fever,
It is used for colds, headaches, colds such as nausea, and late symptoms of colds, but its effect in combination with ibuprofen is unknown.

[0006]

DISCLOSURE OF THE INVENTION The present inventors have aimed to enhance the anti-inflammatory action, analgesic action and antipyretic action of ibuprofen and reduce the gastrointestinal disorders of ibuprofen in a therapeutic agent for colds containing ibuprofen as an active ingredient. Various studies were conducted for the purpose.

[0007]

Means for Solving the Problems As a result of various investigations, the present inventors have found that the Saiko-keishito extract enhances the anti-inflammatory action, analgesic action and antipyretic action of ibuprofen and reduces the gastrointestinal disorders of ibuprofen. Based on this finding, the present invention has been completed.

The drug for treating colds, which contains the ibuprofen and the Saiko-keishito extract of the present invention as active ingredients, will be described in detail below.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION The saiko-keishito extract used in the present invention is, by weight ratio, saiko 2.5 to 8.5 and half summer 1.3 to.
6.5, laurel or cinnamon 1.0 to 4.0, peony root 1.0
~ 6.0, yellow rice 1.0-3.0, and Ojujumu 1.0-5.
0, ginseng 0.7-3.0, licorice 0.3-2.2 and ginger 0.5-2.0, or preferably mixed saiko 4.0-6.0, half-summer 4 .0-5.0, katsura or cinnamon skin 1.5-3.0, peony root 1.5-3.0, yellow corn 1.5-2.5, large jujube 1.5-2.5, carrot 1.5 ~
2.5, licorice 1.0-2.0 and ginger 0.5-1.0
5. A mixed crude drug consisting of, or more preferably Saiko 5.
0, half-summer 4.0, cinnamon skin 3.0, peony root 3.0, yellow rice 2.
It is obtained from a mixed crude drug consisting of 0, Ooju 2.0, ginseng 2.0, licorice 2.0 and ginger 1.0.

Saiko-keishi-to extract is usually used as a concentrated extract or a dry extract powder, and these saiko-keishi-to extract can be produced as follows.

That is, first, water, a water-soluble organic solvent or a mixed solvent thereof is added in an amount of 5 to 25 times, preferably 8 to 20 times by weight that of the above mixed crude drug, and usually 80 to
Heat at 100 ° C for 30 minutes to 2 hours to brew Saiko-keishiyu. Ethanol is preferred as the water-soluble organic solvent.

Next, after the completion of the infusion, the infusion is filtered or centrifuged to remove the infusion slag, and then the concentrated extract is obtained by a conventional concentration means, for example, concentration under reduced pressure, or an ordinary drying means. For example, dried extract powder is obtained by vacuum drying, spray drying or freeze drying.

The remedy for colds of the present invention (hereinafter referred to as the agent of the present invention) is 2 to 15 parts by weight, or preferably 5 to 7 parts by weight, of Saikokeishito extract as a dry weight per 1 part by weight of ibuprofen. It is manufactured by compounding.

The drug of the present invention is a capsule, tablet, or tablet containing ibuprofen and saikokeishito extract as active ingredients.
It includes various solid preparations such as granules, fine granules and powders. These various solid preparations are excipients, usual pharmaceutical additives such as disintegrants, for example, lactose, hydroxypropyl cellulose, corn starch, crystalline cellulose, carmellose calcium, silicic anhydride, synthetic aluminum silicate, It can be produced by a conventional method by appropriately adding magnesium stearate or the like.

Further, in the drug of the present invention, since ibuprofen has a peculiar bitterness, a preparation masking the bitterness is preferable for administration.

As the masking method, known masking methods such as a method of coating a drug with a coating agent (film coating method) or a method of dispersing a drug in a base material to form a matrix (matrix method) are used. .

That is, in the film coating method, the tablets, granules, fine granules or powders obtained as described above are coated with a coating agent such as gastric-soluble, enteric-soluble polymer or water-soluble or water-insoluble polymer. Can be easily performed by applying.

Specific examples of the above-mentioned coating agents include aminoalkylmethacrylate copolymer, polyvinylacetyldiethylaminoacetate, cellulose acetate phthalate, methacrylic acid copolymer, hydroxypropylcellulose, hydroxypropylmethylcellulose.
2910, methyl cellulose, ethyl cellulose and the like can be mentioned.

In the matrix method, ibuprofen and Saiko-keishi-to extract are kneaded with a base consisting of a water-insoluble polymer and / or a water-swelling polymer, granulated, and then ibuprofen and saiko-keishi-to extract. However, it can be carried out by preparing a tablet, granules, fine granules or powder by a conventional method after forming a matrix dispersed in a base comprising the polymer.

Specific examples of the water-insoluble polymer include ethyl cellulose and hydroxypropylmethyl cellulose phthalate. Specific examples of the water-swellable polymer include low-substituted hydroxypropyl cellulose, aminoalkyl methacrylate copolymer, carmellose calcium, sodium carboxymethyl starch, carboxyvinyl polymer and the like.

In addition, water-soluble polymers such as hydroxypropyl cellulose, hardened oils, higher fatty acids such as stearic acid and / or pharmaceutical additives such as sucrose fatty acid esters can be appropriately added to the above-mentioned base.

Among the above solid preparations, ibuprofen and saikokeishito extract are replaced with low-substituted hydroxypropyl cellulose and ethyl cellulose in that the bitterness is effectively masked and the drug effect is rapidly developed. Granules obtained by dispersing them to form a matrix are particularly preferable for administration.

The above granules are blended with 2 to 15 parts by weight, or preferably 5 to 7 parts by weight, of Saikokeishito extract as a dry weight per 1 part by weight of ibuprofen, and these are added to 1 part by weight of ibuprofen. And low-substituted hydroxypropyl cellulose, 1-1.5 parts by weight and 0.3-0.4 parts by weight of ethyl cellulose are added and mixed,
It can be produced by adding ethanol, kneading, granulating, drying and sieving.

The drug of the present invention is administered as a remedy for colds. The dose of the drug of the present invention is not constant depending on the condition, age, body weight, etc. of the patient, but is usually 0.1 to 10 g as an active ingredient per day for an adult, and this is administered once or 2-3 times. Oral administration in divided doses.

[0025]

INDUSTRIAL APPLICABILITY In the drug of the present invention, the plasma concentration of ibuprofen increases as compared with the administration of ibuprofen alone (Test Example 1), so that the anti-inflammatory action of ibuprofen is enhanced. In the drug of the present invention, the analgesic effect of ibuprofen (Test Example 2) and the antipyretic effect (Test Example 3) are enhanced as compared with the case of administration of ibuprofen alone.

Further, since Saiko-keishito extract has an anti-ulcer effect (Test Example 4), the gastrointestinal disorder of ibuprofen is alleviated by the drug of the present invention.

Further, the drug of the present invention has low toxicity (Test Example 5).

The present invention will be described below with reference to test examples.

In the following test examples, ibuprofen was used in a racemic form (R form / S form = 55/45). Also,
As the Saikokeishito extract, a dry extract powder prepared according to Production Example 1 below was used. The drug of the present invention was prepared by appropriately mixing the above-mentioned ibuprofen and Saiko-keishito extract.

Test Example 1 Plasma concentration of ibuprofen: (1) Specimen Drug of the present invention (mixing ratio of ibuprofen and Saikokeishito extract is 1 to 6.11) ibuprofen (2) Test method Male Wistar rats fasted overnight (Weight 220
~ 250 g, 5 animals per group) Canal under anesthesia in the right femoral artery
The blood was applied so that blood could be collected at any time. Each sample was dissolved or suspended in distilled water-5% gum arabic emulsion, and [106.7 mg / kg (ibuprofen 15 mg / k
(equivalent to g), ibuprofen was orally administered at 15 mg / kg], and blood was collected over time after administration, and this blood was collected at 10000 × g, 1
Plasma was obtained after centrifugation for 0 seconds.

1% was added to 50 μl of the plasma thus obtained
Hydrochloric acid 50 μl, hexane / 2-propanol (9/1) 180
20 μl of an internal standard substance (40 μg / ml of m-toluic acid) dissolved in hexane and hexane / 2-propanol (100/1) were added, stirred and centrifuged, and the supernatant was used as a sample solution. This was measured by a high performance liquid column chromatography (HPLC) method using the following measurement conditions, and the concentrations of the R and S forms were calculated from the peak height ratios of the R and S forms to the internal standard substance. .

HPLC measurement conditions: Column: Chiralcel TMOD (manufactured by Daicel Chemical Industries, Ltd.,
4.6mm × 250mm) Column temperature: 35 ℃ Mobile phase: Hexane / 2-propanol / 1% trichloroacetic acid
(100/1 / 0.01) Flow rate: 1.0 ml / min Detection: UV220nm (3) Test results The concentration transition of S-body (active body) in rat plasma is shown in Fig. 1 and R
Changes in body concentration are shown in FIG.

As is clear from FIG. 1, the plasma concentration of S-body (active substance) in the drug administration group of the present invention tended to increase immediately after the administration as compared with that in the ibuprofen administration group, and particularly 10 to 15 administrations In the minute, a significant increase was observed.

As is clear from FIG. 2, the plasma concentration of R-form in the drug administration group of the present invention is lower than that of S-form because the R-form is converted into S-form in the body. However, as in the case of the above S-form, an increase tendency was observed immediately after the administration, as compared with that of the ibuprofen administration group.
A significant increase was observed at ~ 15 minutes.

Test Example 2 Analgesic effect: (1) Specimen Agent of the present invention (mixing ratio of ibuprofen and Saiko-Keishi-to extract is 1 to 6.67) Ibuprofen Saiko-Keishi-to extract (2) Test method Five-week-old ddY system fasted overnight Male mouse (weight 20-26
g, 1 group 11 to 16 animals), each sample was dissolved or suspended in distilled water-5% gum arabic emulsion and the dose (0.1
(ml / 10g) was orally administered. 1 hour after administration, 0.7% acetic acid 0.1
ml / 10g was intraperitoneally administered. Next, 5 minutes after acetic acid administration, 2
15 minutes mouse writhing until 0 minutes
The inhibitory rate was calculated according to the following formula from the licing number of the control group [group in which only distilled water-5% gum arabic emulsion was orally administered (sample non-administered group)]. The ED ₅₀ value was determined by the Probit method with 50% or less of the average licing number of the control group being effective.

[0036]

[Equation 1] (3) Test results The results are shown in FIG. 3 and Table 1.

[0037]

[Table 1] The ED ₅₀ value of the drug of the present invention is 359.8 mg / kg, but when compared by the amount of ibuprofen, the efficacy was increased by about 1.3 times as compared with the case of administering ibuprofen alone.

Test Example 3 Antipyretic Action: (1) Sample Same as Test Example 2. (2) Test method 2 subcutaneously on the back of Wistar male rats (body weight 182-222 g)
10 ml / kg of 0% dry yeast saline was injected. After fasting overnight after yeast injection, after 17 hours, each sample was dissolved or suspended in distilled water-5% gum arabic emulsion in rats (6 rats per group) whose rectal temperature increased by 1.2 ° C or more. Inventive drug
11.5 mg / kg (equivalent to ibuprofen 1.5 mg / kg), ibuprofen 1.5 mg / kg, and saikokeishito extract 12.5 mg / kg]. Then, the rectal temperature was measured every 1 hour after the administration of the sample until 5 hours later.

The rectal temperature of the control group [group in which only distilled water-5% gum arabic emulsion was orally administered (sample not administered group)] was measured in the same manner as above. (3) Test results The results are shown in FIGS. 4 and 5.

As is clear from FIG. 4, in the ibuprofen administration group, a significant decrease in rectal temperature was observed 1 hour after administration, but no difference was observed from the control group after 2 hours.
On the other hand, in the drug administration group of the present invention, a significant decrease in rectal temperature was observed from 1 to 3 hours after the administration, showing that the antipyretic action of ibuprofen was enhanced.

Further, as shown in FIG. 5, the rectal temperature of the Saiko-keishito extract-administered group remained almost unchanged.

Test Example 4- (1) Anti-ulcer action: (1) Specimen Saiko-keishi-to extract (2) Test method Male SD rats (body weight: 174-206 g, group 8-9) fasted overnight
The test sample was suspended in distilled water, and the dose shown in FIG. Aspirin 200 mg / kg 30 minutes after oral administration
Was orally administered to induce aspirin ulcer. Four hours later, the rat was sacrificed, and the stomach was immediately removed and fixed with formalin. After incising the major bay, the length of damage (mm) was measured with a stereomicroscope, and the total length of damage per animal was taken as the ulcer index.

The ulcer index was determined in the same manner as described above for the control group [group in which only distilled water-5% gum arabic emulsion was orally administered (sample not administered group)]. (3) Test result The result is shown in FIG.

As is apparent from FIG. 6, the gastric mucosal damage caused by aspirin was suppressed by the administration of the Saikokeishito extract. Therefore, in the drug of the present invention containing ibuprofen and saikokeishito extract, the gastrointestinal disorder of ibuprofen is reduced by the saikokeishito extract.

Test Example 4- (2) Anti-ulcer action: (1) Specimen Saiko-keishi-to extract (2) Test method Male SD rats (body weight 184-208 g, group 5-6) fasted overnight
The test sample was suspended in distilled water and orally administered at the dose shown in FIG. 30 minutes after oral administration ibuprofen 100m
Oral administration of g / kg induced ibuprofen ulcer.
Four hours later, the rat was sacrificed, and the stomach was immediately removed and fixed with formalin. Length of damage after incision in great bay
(mm) was measured with a stereoscopic microscope, and the total length of damage per animal was taken as the ulcer index.

Further, the ulcer index was determined in the same manner as described above for the control group [group in which only distilled water was orally administered (sample non-administration group)]. (3) Test results The results are shown in Fig. 7.

As is clear from FIG. 7, administration of the Saiko-keishito extract significantly suppressed the gastric mucosal damage caused by ibuprofen. Therefore, in the drug of the present invention containing ibuprofen and saikokeishito extract, the gastrointestinal disorder of ibuprofen is reduced by the saikokeishito extract.

Test Example 5 Acute toxicity: (1) Specimen Compound of the present invention (mixing ratio of ibuprofen and Saiko-keishito extract is 1 to 6.44) (2) Test method Male F344 / Du Crj rats (weight: 76 to 81 g, 1 Samples were suspended in distilled water in 5 animals per group, and 2000 mg / kg was orally administered, and the presence or absence of death, general condition, and changes in body weight were observed for 7 days. At the end of the observation period, the presence or absence of abnormalities in various organs of the whole body was visually observed. (3) Test Results No mortality was observed even when the drug of the present invention was orally administered at 2000 mg / kg (LD ₅₀ value> 2000 mg / kg). Also, during the observation period,
There was no abnormality in the general condition, and the weight also showed a steady increase.

No macroscopic changes in major organs were observed even at autopsy at the end of the observation period.

[0050]

EXAMPLES The present invention will be described below with reference to production examples and examples.

Production Example 1 Production of Saiko-keishi-to extract powder: 1.25 kg of saiko, 1.0 kg of summer, 0.75 kg of cinnamon bark, 0.75 kg of peony, 0.5 kg of yellow rice, 0.5 kg of ginseng, carrot To a mixed crude drug consisting of 0.5 kg, licorice 0.5 kg and ginger 0.25 kg, 60 l of purified water was added and heated at about 100 ° C. for 1 hour.
The decoction was filtered, concentrated under reduced pressure, and then spray-dried to obtain 1.47 kg of dried Saiko-keishi-to extract powder (yield: 24.5%.
).

Example 1 Granules: (Formulation) 10 parts by weight ibuprofen 10 parts by weight dried extract of Saiko-keishi-to 64 parts by weight Lactose 9 parts by weight Low-substituted hydroxypropylcellulose 13 parts by weight Ethylcellulose 3 parts by weight Magnesium stearate 1 part by weight Each component from ibuprofen to ethyl cellulose was thoroughly mixed, and 30 parts by weight of anhydrous ethanol was added and kneaded.
Granulate by a wet extrusion granulation method, dry and sieve to obtain a granulated product. Magnesium stearate is added to this granulated product and mixed to obtain a granule.

Example 2 Granules: (Formulation) Ibuprofen 10 parts by weight Saiko-keishito dried extract powder 67 parts by weight Lactose 5 parts by weight Low-substituted hydroxypropylcellulose 14 parts by weight Hydroxypropylcellulose 3 parts by weight Magnesium stearate 1 Parts by weight Ibuprofen up to hydroxypropyl cellulose are thoroughly mixed, 30 parts by weight of anhydrous ethanol is added and kneaded, granulated by a wet extrusion granulation method, dried and sieved to obtain a granulated sieve. Get the granules. Magnesium stearate is added to this granulated product and mixed to obtain a granule.

Example 3 Granules: (Formulation) Ibuprofen 10 parts by weight Saiko-keishi-to dried powder 67 parts by weight Lactose 12 parts by weight Low-substituted hydroxypropylcellulose 7 parts by weight Hydroxypropylcellulose 3 parts by weight Magnesium stearate 1 Parts by weight Ibuprofen up to hydroxypropyl cellulose are thoroughly mixed, 30 parts by weight of anhydrous ethanol is added and kneaded, granulated by a wet extrusion granulation method, dried and sieved to obtain a granulated sieve. Get the granules. Magnesium stearate is added to this granulated product and mixed to obtain a granule.

Example 4 Granules: (Formulation) Ibuprofen 10 parts by weight Saiko-keishi-to dry extract powder 67 parts by weight Lactose 14 parts by weight Carmellose calcium 5 parts by weight Hydroxypropyl cellulose 3 parts by weight Magnesium stearate 1 part by weight Ibuprofen or less hydroxy Each component up to propyl cellulose is thoroughly mixed, 30 parts by weight of anhydrous ethanol is added and kneaded, granulated by a wet extrusion granulation method, dried and sieved to obtain a granulated product. Magnesium stearate is added to this granulated product and mixed to obtain a granule.

Example 5 Fine Granules: (Formulation) Ibuprofen 12 parts by weight Saiko-keishi-to dried powder 72 parts by weight Crystalline cellulose 7 parts by weight Synthetic aluminum silicate 7 parts by weight Magnesium stearate 2 parts by weight Each of the above components Is thoroughly mixed, and the mixture is made into a plate-like product by a compression molding machine, crushed into granules with an oscillator, and sieved to obtain fine granules.

Example 6 Tablets: (Formulation) 8 parts by weight of ibuprofen 8 parts by weight of dried extract of Saiko-keishi-to 48 parts by weight of lactose 20 parts by weight of corn starch 6 parts by weight of synthetic aluminum silicate 8 parts by weight of calcium carmellose 6 parts by weight of magnesium stearate 1 3 parts by weight Hydroxypropyl methylcellulose 2910 3 parts by weight After adding 28 parts by weight of 99% ethanol to ibuprofen, dried saiko-keishito dry extract powder, lactose, corn starch and synthetic aluminum silicate, and thoroughly kneading,
It is crushed and granulated with a hammer mill type crusher and dried to obtain a granulated product. Carmellose calcium,
Magnesium stearate is added and mixed, and this mixture is tabletted into 300 mg tablets to give tablets. The tablets are then loaded with hydroxypropyl methylcellulose 2910.
Apply a film consisting of to make a film-coated tablet.

[Brief description of drawings]

FIG. 1 is a graph showing changes in the plasma concentration of S-body when the drug of the present invention or ibuprofen is orally administered to rats.

FIG. 2 is a graph showing changes in the plasma concentration of R-form when the drug of the present invention or ibuprofen is orally administered to rats.

FIG. 3 is a graph showing a dose-response curve of acetic acid licing inhibition rate when the drug of the present invention, saikokeishito extract and ibuprofen were orally administered to mice.

FIG. 4 is a graph showing changes in rectal temperature with time when the drug of the present invention, ibuprofen, was orally administered to yeast-fevered fever rats.

FIG. 5 is a graph showing changes in rectal temperature with time when the Saiko-keishito extract is orally administered to yeast-fevered rats.

FIG. 6 is a view showing a dose-response curve of gastric mucosal disorder (aspirin ulcer) when the Saiko-keishito extract is orally administered to rats.

FIG. 7 is a view showing a dose-response curve of gastric mucosal disorder (ibuprofen ulcer) when the Saiko-keishito extract is orally administered to rats.

[Explanation of symbols]

●: The drug administration group of the present invention ○: Ibuprofen administration group △: Saikokeishito extract administration group □: Control group *: Significantly different from the control group at p <0.05 (Dunne
tt's test) **: Significantly different from control group at p <0.01 (Dunne
tt's test) #: p <0.05 significantly different from ibuprofen administration group (Dunnett's test) ##: p <0.01 significantly different from ibuprofen administration group (Dunnett's test)

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Internal reference number FI technical display location A61K 47/38 L (72) Inventor Muneto Matsuda 1-8 Tsuzuyamadai, Tomitabayashi-shi, Osaka -207 (72) Inventor, Motoki Hiura 1-6-7-203, Tomobuchi-cho, Miyakojima-ku, Osaka-shi, Osaka (72) Inventor Akira Yamashita 2--1-30-401, Takasu-cho, Nishinomiya-shi, Hyogo

Claims (7)

[Claims] 1. A therapeutic agent for colds, which comprises ibuprofen and Saiko-keishito extract as active ingredients. 2. The therapeutic agent for colds according to claim 1, wherein 1 to 15 parts by weight of ibuprofen is mixed with 2 to 15 parts by weight of a dry extract of Saiko-keishito extract. 3. The cold remedy according to claim 1, which comprises 1 to 7 parts by weight of ibuprofen and 5 to 7 parts by weight of a dry product of Saiko-keishito extract. 4. By weight ratio, saiko 5.0, half-summer 4.0, cinnamon skin 3.0, peony medicine 3.0, yellow rice 2.0, ojutsu 2.0, carrot 2.0, licorice. The remedy for colds according to any one of claims 1 to 3, which comprises a Saiko-keishito extract obtained from a mixed crude drug consisting of 2.0 and ginger 1.0. 5. A solid preparation in which the bitterness of ibuprofen is masked, which is obtained by dispersing ibuprofen and Saiko-keishito extract in a water-insoluble polymer and a water-swellable polymer. The cold remedy according to any one of 1. 6. The cold remedy according to claim 5, wherein the solid preparation is a granule. 7. The cold remedy according to claim 6, wherein the water-insoluble polymer is ethyl cellulose and the water-swellable polymer is low-substituted hydroxypropyl cellulose.