JP2600653B2 - Oral preparation - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to an oral preparation having an excellent effect of adsorbing and removing harmful substances and malodorous substances generated or present in the digestive tract.

2. Description of the Related Art Problems to be solved by the prior art and the invention It has been known that activated carbon is conventionally used as an oral preparation and has an effect of adsorbing harmful substances in the digestive tract. For example, activated carbon is embedded in an agar gel by a water-in-oil (W / O) emulsion method, and the activated carbon is converted into beads to form a formulation that is easy to take, and applied as an emergency detoxifier (Pharmacia, V.
ol.21, NO.5, 414-417, 1985), in order to make it easy to take and to effectively exert the adsorption effect of activated carbon in the intestine, petroleum pitch-based spherical activated carbon can be made alkaline with sodium picosulfate. It is microencapsulated with a soluble polymer substance to be useful for the treatment of uremia and liver injury (Japanese Patent Laid-Open No. 57-31864), and similarly, activated carbon for oral administration is coated with a sugar coating or stored in a capsule. It has been proposed to use it for detoxification of acute drug poisoning (JP-A-59-193826). Conventionally, activated carbon microcapsules having 5 to 85% of activated carbon based on the total weight, and having about 10 to 30 mm of micropores formed in the outer layer of the polymer to prevent deterioration of the adsorption ability of activated carbon. It has also been proposed to use in fields such as pharmaceuticals (JP-A-53-30988).

As described above, it has been conventionally known that activated carbon is used as a pharmaceutical adsorbent, but an oral preparation having a higher adsorption effect is desired. In particular, it is difficult to deodorize odorous substances generated by metabolism in the gastrointestinal tract, for example, garlic odor by simply orally administering activated carbon. Therefore, it is required to adsorb and deodorize such odorous substances.

The present invention has been made in view of the above circumstances, and an object of the present invention is to provide an oral preparation that is excellent not only in the effect of adsorbing toxic substances in the digestive tract but also in the effect of deodorizing malodorous substances.

Means and Action for Solving the Problems The present inventors have conducted intensive studies to achieve the above object, and as a result, adsorbents and at least one plant extract selected from rosemary, Japanese gourd or clove It has been found that an oral preparation having an effect of adsorbing and removing toxic substances generated or present in the digestive tract and an effect of deodorizing malodorous substances can be obtained by using in combination.

That is, when the above extract is used in combination with adsorbents such as activated carbon, silica gel, zeolite, diatomaceous earth, activated clay, and activated alumina, harmful substances in the digestive tract can be effectively adsorbed and removed, and malodorous substances such as methyl mercapton can be obtained. The deodorizing effect of garlic is increased, and it is possible to effectively adsorb and deodorize malodorous substances in the gastrointestinal tract as compared with the case where the adsorbent is taken alone, for example, to deodorize garlic odor etc generated by metabolism in the gastrointestinal tract. It has been found that bad breath from the gastrointestinal tract can be prevented and eliminated.

To further elaborate on this point, it has been conventionally known that plant extracts are used for removing bad breath, and the plant extracts are blended into an oral composition such as dentifrice and the like. It has been proposed to prevent and eliminate bad breath by cleaning (JP-A-57-38708, JP-A-57-56415, JP-A-57-56416, JP-A-57-56416).
203445, 58-39615, 58-134013, 59-13712, 50-
However, it is difficult to simply remove the garlic odor and the like generated by metabolism in the digestive tract by cleaning the oral cavity. Thus, the bad odor derived from the malodorous components in the digestive tract is removed by the conventional bad odor prevention method. It cannot be done. Further, as described above, it is difficult to reliably adsorb and deodorize such malodorous components in the digestive tract only by taking an adsorbent such as activated carbon, but the adsorbent such as activated carbon and the extract When used in combination, harmful substances and malodorous substances generated or present in the digestive tract can be reliably adsorbed and deodorized, so that bad breath derived from these substances can be prevented and eliminated.

Conventionally, an adsorbent such as activated carbon has been used as a deodorant component for removing malodorous components in the air. In this case, an adsorbent such as activated carbon is used in combination with another deodorant substance. For example, Japanese Patent Application Laid-Open No. 49-31831 proposes that chlorella or chlorophyll powder adsorbed on activated carbon or diatomaceous earth is used for purification of automobile exhaust gas. It has been proposed that the extract be absorbed by a carrier such as silica gel, diatomaceous earth, activated carbon, and the like and used as an air purifier.
No. 8725 proposes to absorb or adsorb and remove malodorous gas discharged from a human waste treatment plant or a sewage treatment plant by using a malodor removing agent using tannic acid and / or a tannic acid derivative in combination with activated carbon. No. 75322 proposes a deodorizing filter for an air purifier using an extract of a camellia family or camphoraceous plant and activated carbon in combination.

However, the use of an adsorbent such as activated carbon and the above extract in combination with the above-mentioned extract as an oral preparation, such an oral preparation effectively removes harmful substances and malodorous substances in the gastrointestinal tract, and in particular, malodorous substances in the gastrointestinal tract. The present inventors have never found any knowledge of reliably preventing bad breath derived from the present invention, and have found it for the first time.

 Hereinafter, the present invention will be described in more detail.

The oral preparation according to the present invention is a breath freshener, an emergency detoxifier,
It is prepared and applied as an anti-aging agent, an obesity inhibitor, a health food (such as a troche), and uses an adsorbent together with an extract of at least one plant selected from rosemary, Japanese gourd or clove. It becomes.

The adsorbent used in the present invention may be any non-toxic and orally administrable adsorbent. In particular, powdered or granular materials such as activated carbon, silica gel, zeolite, diatomaceous earth, activated clay, and activated alumina Is preferably used. In this case, these adsorbents may be used alone or in combination of two or more.

In addition, the deodorant used in the present invention, as described above,
It is an extract of at least one plant selected from rosemary, Japanese gourd or clove, and the deodorant active ingredient contained in these extracts can be isolated from the extract or synthesized for use.

Here, the above-mentioned extract is obtained by adding at least one or more kinds selected from rosemary, Japanese gourd or clove to water, methanol, ethanol, acetone, ethyl ether, n
-It is obtained by extraction with one or more organic solvents such as hexane. The deodorant active ingredients contained in these extracts are carnosol, carnosic acid, rosmacour, shikonin, bridylin, hematoxylin, baicalin, baicalen, tannin, tannic acid and the like.

The oral preparation of the present invention uses the adsorbent and the extract as described above in combination, and in this case, the combination ratio of the adsorbent and the extract is 2: 1 to 200: 1 by weight. This makes it possible to more effectively adsorb and remove harmful substances and malodorous substances existing or generated in the digestive tract, such as indole, amine, nitroso compound, hydrogen sulfide, mercaptan, etc., and to deodorize, especially in the oral cavity. It is more effective to remove and deodorize malodorous components generated by metabolism, such as garlic odor, which are difficult to prevent bad breath by cleaning alone.

The oral preparation of the present invention can be formulated into various forms, such as powders and granules, tablets, capsules or drops,
It can be made into various forms that can be administered orally, but the adsorbent and the above-mentioned extract are used individually or in a state where both are mixed together, coated with an appropriate membrane material and microencapsulated. It is also preferable that in this case, it is also possible to use a membrane material that is insoluble and neutral or alkaline and dissolves in an acidic manner to form a positively soluble capsule, and by thus encapsulating the adsorbent and the extract, , These adsorbents, the use of powdery extract as an extract, can be used to suppress scattering, or if the extract has a bite or unpleasant taste, it can be included, so it is easy to take orally In the case of positively soluble capsules, the capsules do not dissolve in the stomach, so that they can be implanted with adsorbents, rosemary, orchids or cloves. The extract does not decompose or degrade with acid in the stomach, and the active ingredient directly acts on harmful substances and odorous substances that are generated or present in the intestine. Obtainable.

Here, the encapsulation can employ a usual method, and there is no limitation on the film material, and a generally used film material can be used. Specifically, proteins such as gelatin, casein, albumin, etc., natural polymer substances such as gum arabic, alginic acid, carrageenan, dextran, pullulan, etc .; Synthetic polymer substances, synthetic polymer substances such as polyvinyl alcohol, polyvinylpyrrolidone and the like, and examples of the enteric film material include cellulose acetate phthalate, hydroxypropyl methylcellulose, and methyl methacrylate-methacrylic acid copolymer. It should be noted that a translucent or porous membrane can be used as the membrane material to accelerate the solubility of the capsule.

If necessary, the oral preparation of the present invention may contain, in addition to the adsorbent and the above-mentioned extract, various components according to the kind of the oral preparation and the like.

The dosage of the oral preparation of the present invention may be, for example, an adsorbent.
It is preferable that the extract be about 33 mg / kg body weight and the extract be about 8 mg / kg body weight.

Effect of the Invention As described above, the oral preparation of the present invention uses an adsorbent and an extract of at least one plant selected from rosemary, Japanese gourd or clove in combination,
It can effectively deodorize and remove harmful substances and malodorous substances generated or present in the digestive tract, and especially malodorous substances (garlic odor etc.) generated by metabolism that is difficult to prevent bad breath by just cleaning the mouth. It is effective for deodorizing. In this case, if the adsorbent and the above extract are enteric-encapsulated to prepare an oral preparation, it is easy to take, and the adsorbent and the plant extract of any one of rosemary, Japanese gourd or Clove are used in the stomach. As a result, it is possible to reach the intestines without decomposition and deterioration, thereby having the effect of more reliably adsorbing and removing harmful substances, malodorous components, etc. present or generated in the intestine in the digestive tract and deodorizing.

Hereinafter, the present invention will be described specifically with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples.

[Examples 1 to 6] Activated carbon, silica gel, zeolite, diatomaceous earth, activated clay, and activated alumina were used as adsorbents, and 2 mg of each was placed in a test tube having a capacity of 25 ml.
1 ml of an aqueous solution containing a concentration of mg / ml was added to each test tube to prepare a sample. As the rosemary extract, rosemary extracted with 30% ethanol and dried was used.

Next, the deodorizing effect of these samples was evaluated by the following method.

Deodorizing effect evaluation method 0.05M phosphate buffer (pH 7.2) 5m into the test tube containing the sample
l and 1 ml of 10 ppm methyl mercaptan solution, and add
Incubated for minutes. After the incubation,
Methyl mercaptan in the head space was measured by gas chromatography, and the methyl mercaptan deodorizing rate of each sample was determined by each formula.

C: The amount of methyl mercaptan in the headspace in the control system containing no adsorbent and no extract.

S: The amount of methyl mercaptan in the sample headspace.

 The results are shown in Table 1.

From the above results, activated carbon, silica gel, zeolite,
It was confirmed that the diatomaceous earth, activated clay and activated alumina used as adsorbents and the extract of rosemary in combination were all excellent in deodorizing effect.

[Example 7, Comparative Examples 1 and 2] 5 g of gelatin powder was dissolved in 100 ml of warm water, and 2 g of activated carbon powder and 0.5 g of dried gourd extract as a plant extract were added and dispersed well. Then, 0.2% as surfactant
A mixed solution of ethyl acetate and chloroform containing polyoxyethylene hydrogenated castor oil (ethyl acetate: chloroform =
3: 4) was prepared and cooled sufficiently, and the above-mentioned dispersion liquid was dropped and dispersed in this mixed solution, followed by filtration to obtain microcapsules (A).

For comparison, microcapsules (B) or (C) containing no dried gourd extract or activated carbon powder were obtained in the same manner.

The dried gourd extract used was a gourd that had been extracted from water and the resulting extract was dried.

Example 8, Comparative Examples 3 and 4 4 g of cellulose acetate was dissolved in 40 ml of methylene chloride, and 6 g of activated carbon and 0.1 g of clove extract were added and dispersed. Next, this dispersion was added to 600 ml of an aqueous solution in which 3 g of sodium laurylbenzenesulfonate was dissolved while stirring at room temperature. Continue stirring and evaporate the solvent,
Include activated carbon with solid gelled cellulose acetate,
Activated carbon microcapsules with a semipermeable cellulose acetate membrane were deposited. This was filtered, washed with water, and dried by ventilation at 40 ° C. to obtain microcapsules (D).

For comparison, microcapsules (E) or (F) containing no clove extract or activated carbon were obtained in the same manner.

As the extract of the clove, an extract obtained by performing an extraction treatment with 30% ethanol and drying the obtained extract was used.

[Example 9, Comparative Example 5] 1% ethanol solution of rosemary dried extract (1/100 volume) was putsley on activated carbon powder, then sprayed with an aqueous sodium bicarbonate solution of cellulose acetate phthalate containing sodium pyrosulfate to give activated carbon. On the other hand, microcapsules (G) to which cellulose acetate phthalate was attached in an amount of 0.3 to 2% by weight were obtained.

This microcapsule was subjected to a disintegration test according to the disintegration test method of the Japanese Pharmacopoeia (tenth revision).
About 7.5) and confirmed to be enteric coated capsules.

For comparison, a microcapsule (H) containing only rosemary extract containing no activated carbon was obtained in the same manner.

In addition, as a rosemary dry extract, what extracted the hexane extraction residue of rosemary with ethanol, and dried the obtained extract was used.

Next, these microcapsules (A) to (H)
Each 0.1 g was put into a 25 ml test tube, and the deodorizing effect of methyl mercaptan was evaluated in the same manner as in Examples 1 to 6.

The results are shown in Table 2. The results are shown as the average ± SD of the values measured three times for each microcapsule.

From the above results, the microcapsules containing the adsorbent and the extracts of rosemary, Japanese gourd or clove each have an excellent deodorizing effect compared to the microcapsules containing only the adsorbent or the extract. Was confirmed.

 Hereinafter, formulation examples are shown.

(Formulation example)

A 50% sucrose (containing 2% ethylene glycol) solution is sprayed on the microcapsules obtained in Example 7 and dried to obtain sugar-coated capsules. This administers 1 g at a time.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification number Agency reference number FI Technical display location A61K 35/78 A61K 35/78 C

Claims (3)

(57) [Claims] 1. An oral preparation applied to the digestive tract, comprising a combination of an adsorbent and an extract of at least one plant selected from rosemary, red gourd or clove. 2. The oral preparation according to claim 1, wherein the adsorbent and the extract are covered with a film material and encapsulated. 3. The oral preparation according to claim 1, wherein activated carbon, silica gel, zeolite, diatomaceous earth, activated clay or activated alumina is used as the adsorbent.