JP2717509B2 - Bitterness reducing agent and method for reducing bitterness - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a bitterness reducing agent and a method for reducing bitterness using the same. In particular, the present invention relates to a bitterness reducing agent capable of effectively reducing bitterness by adding it to foods, medicines, or cosmetics having bitterness, and a method for reducing bitterness using the same.

[0002]

2. Description of the Related Art There are many foods, pharmaceuticals or cosmetics containing bitter substances. In particular, most of pharmaceuticals have a bitter substance and are painful when taken orally. Therefore, reducing bitterness has become a major formulation challenge. As a method of reducing bitterness in currently used preparations, for example, a method of adding a sweetener and a flavoring agent (JP-A-2-56416: a method using aspartame), microencapsulation, and a gastrosoluble coating agent A method using a powder coating agent,
Various methods such as a method of chemically modifying a drug and a method of adding an inclusion compound (JP-A-3-236316) are exemplified. However, both methods have drawbacks such as difficulty in sufficiently suppressing bitterness, and use of only a limited number of drugs. Furthermore, in addition to the above methods, a method of adding an oil component to a drug having a bitter taste, particularly a method of adding lecithin (phosphatidylcholine) or kephalin alone or in a mixture (Japanese Patent Publication No.
No. 5-8966) and a method of adding lecithin (phosphatidylcholine) (Japanese Patent Application Laid-Open No. 62-265234) have also been proposed. However, according to the study by the present inventors, even the above method has not yet sufficiently reduced bitterness. In particular, it is often difficult for infants and the elderly to take a solid preparation when taking a drug. In such a case, a liquid form such as a syrup is used. However, at present, there is no effective method for removing the bitter taste of a liquid drug such as a syrup.

[0003] Foods may also contain various bitter substances such as bitterness of amino acids and peptides obtained from protein degradation products, bitterness present in fruit juice, bitterness derived from added flavors, and the like. The presence of the substance often reduces the quality of the food. As a method for removing bitterness in food, for example, a method using an adsorbent (JP-A-55-108254), a method using an inclusion compound (JP-A-61-40260), and a method using a sweetener A method of adding (JP-A-60-9774) is known. However, there are many problems that these methods often cannot sufficiently suppress bitterness and that the quality of food taste is easily changed.

[0004] Furthermore, it is preferable that cosmetics such as a lotion used for the face, a mouthwash used in the oral cavity, and a toothpaste do not usually have a bitter taste. However, some of the surfactants and fragrances (flavors) as components thereof have a bitter taste, and the types and amounts thereof may be limited due to the bitterness when used. Conventionally, bitterness has been removed by adding a sweetener or a specific flavor to alleviate the bitterness. However, such a method is often inappropriate, and a component exhibiting strong bitterness has a sufficient effect. Is often not obtained.

[0005]

An object of the present invention is to effectively reduce the bitterness of pharmaceuticals, foods, or cosmetics containing a bitter substance, and to change the taste of foods safely and safely. It is an object of the present invention to provide a bitterness reducing agent which can be used without any problem and a method for reducing bitterness using the same.

[0006]

Generally, a substance having a bitter taste has a hydrophobic group, and by the action of the hydrophobic group, the lipid-lipid and lipid-protein lipids present on the taste receptor membrane of the taste cells of the tongue are present. People who ingest the substance tend to
Bitterness is felt through this adsorption action. It has also been confirmed in studies using liposomes composed of phospholipids that substances having stronger bitterness have higher affinity for lipids. That is, when a substance having a bitter taste is added to the liposome in which the fluorescent dye has been incorporated, the substance having a bitter taste is adsorbed to the liposome membrane, thereby releasing the fluorescent dye. It has been confirmed that the emission of the fluorescent dye is greater for a substance exhibiting a stronger bitter taste. That is,
It has the property that bitter substances are easily adsorbed on the phospholipid membrane.

[0007] The present inventors have conducted intensive studies focusing on the bitter taste-receiving mechanism of the substance having a bitter taste in the taste organ and the interaction between the bitter substance and lipid. As a result, they have found that acidic phospholipids and lysoacid phospholipids are very effective in reducing bitterness. It has not been known that such acidic phospholipids or lyso forms thereof independently exhibit a strong bitter taste reducing action.

Accordingly, the present invention resides in a bitterness reducing agent comprising an acidic phospholipid or its lyso form as an active ingredient.

The present invention also provides a method for reducing bitterness comprising adding the above-mentioned bitterness reducing agent as an active ingredient to a food having a bitter taste in an amount of 0.05 to 30% by weight based on the total amount of the food. There is also.

Further, the present invention provides a method for reducing bitterness, which comprises adding the above-mentioned bitterness reducing agent as an active ingredient to a drug having bitterness in an amount of 0.01 to 60% by weight based on the total amount of the drug. There is also.

The present invention further provides a bitter taste reducing agent characterized in that the above-mentioned bitterness reducing agent is added as an active ingredient to a cosmetic product having a bitter taste in an amount of 0.05 to 30% by weight based on the total amount of the cosmetic product. There is also a law.

The present invention is preferably in the following modes. (1) The acidic phospholipid and its lyso form are selected from the group consisting of phosphatidylserine, phosphatidic acid, phosphatidylinositol, phosphatidyl glycerol, cardiolipin, and these lyso forms. (2) The acidic phospholipid or lyso-form is present in the lipid mixture, and the amount of neutral lipid in the lipid mixture is 25% by weight or less (particularly 20% by weight or less).

(3) The acidic phospholipid or its lyso form is present in the lipid mixture, and the acidic phospholipid or its lys form in the lipid mixture is contained in the lipid mixture in an amount of 60% by weight or more (particularly 70% by weight or more). )include. (4) the acidic phospholipid or its lyso-form is phosphatidic acid or lysophosphatidic acid, and the phosphatidic acid and / or lysophosphatidic acid is 5% by weight or more (more preferably 20% by weight or more, particularly preferably 50% by weight or more). (5) The acidic phospholipid or its lyso form is present in the lipid mixture, and the amount of the neutral phospholipid in the lipid mixture is not more than twice the content of the phospholipid (more preferably 1/2).
Or less, particularly 1/5 or less, and most preferably 1/50 or less).

(6) The above-mentioned bitterness-reducing agent is added to a food having a bitter taste as an active ingredient in an amount of 0.
1-20% by weight (preferably 0.5-15% by weight, more preferably 1-10% by weight, particularly preferably 1-5% by weight) is added.

(7) The above-mentioned bitterness reducing agent is added as an active ingredient to a drug having a bitter taste in an amount of 0.05 to 50% by weight (preferably 0.1 to 30% by weight, more preferably 0.1 to 30% by weight). Is added in an amount of 0.5 to 20% by weight, particularly preferably 1 to 10% by weight.

(8) In a cosmetic having a bitter taste, the above-mentioned bitterness reducing agent is used as an active ingredient in an amount of 0.1 to 20% by weight (preferably 0.5 to 15% by weight, based on the total amount of the cosmetic).
More preferably 1 to 10% by weight, particularly preferably 1 to 5% by weight.
% By weight).

Hereinafter, the bitterness reducing agent of the present invention will be described. The bitterness reducing agent of the present invention contains an acidic phospholipid or its lyso form as an active ingredient. The acidic phospholipids are those which have a negative total charge in physiological saline (pH 7.0). Examples of acidic phospholipids include phosphatidylserine, phosphatidic acid, phosphatidylinositol, phosphatidylglycerol, and cardiolipin. Examples of the lyso form (ie, lyso acid phospholipid) include lysophosphatidylserine, lysophosphatidic acid, lysophosphatidylinositol, and lysophosphatidylglycerol.

The acidic phospholipid or its lyso form used in the bitterness reducing agent of the present invention can be obtained by extracting and separating from soybean, egg yolk, wheat germ, various animal organs and various plant tissues. . Examples of the extraction method that can be used include extraction with an organic solvent using a difference in polarity. Examples of the separation method include a method of adsorbing on a silica gel column and then eluting with an organic solvent. In order to obtain an acidic phospholipid or a lyso form thereof, a method in which a phospholipid analog separated by extraction, separation, and purification is modified by chemical modification and / or enzymatic treatment can also be used. As a specific method thereof, phospholipase D derived from plants such as oil seeds (Japanese Patent Application Laid-Open No. 2-312552), cabbage, rice bran or the like, or phospholipase D produced by microorganisms (Japanese Patent Application Laid-Open No. 2-312551) is used. A method of hydrolyzing phosphatidylcholine, which is a neutral phospholipid, to obtain phosphatidic acid, or transesterifying a phosphate group using phospholipase D to convert phosphatidylcholine into phosphatidylglycerol (Japanese Patent Application Laid-Open No. 3-22991) or phosphatidyl. A method of converting to serine or the like can be mentioned.

In the bitterness reducing agent of the present invention, a chemically synthesized acidic phospholipid or its lyso form can also be used. Specific synthesis methods include phosphorylation of diglyceride, phosphorylation of monoglyceride, fatty acid esterification of glycerophosphoric acid, phosphorylation of monoglyceride, and fatty acid esterification of glycerophosphate. Examples of acidic phospholipids and lyso forms thereof obtained by the chemical synthesis method as described above include monoacylglyceromonophosphate, monoacylglycerodiphosphate, diacylglyceromonophosphate, bisphosphatidic acid, bisphosphatidyl monophosphatidic acid, Bisphosphatidyl lysophosphatidic acid and the like can be mentioned. Further, hydrogenated acidic phospholipids and hydrogenated lysoacid phospholipids can also be used.

The acidic phospholipid or its lyso form, which is an active ingredient of the bitterness reducing agent of the present invention, can be obtained from natural products or by chemical synthesis as described above. Therefore, the acidic phospholipid or its lyso form is obtained as a lipid mixture and is often used as a lipid mixture. In that case, in order to obtain a higher bitterness-reducing effect, it is preferable that the content of the acidic phospholipid or its lyso form is large, and specifically, the content is 20% by weight or more in the lipid mixture. And more preferably 40% by weight or more. In particular, it is preferably contained in an amount of 60% by weight or more and 70% by weight or more. In addition, among acidic phospholipids and lyso-forms thereof, phosphatidic acid and lysophosphatidic acid have been confirmed to have a strong bitterness-reducing action, and therefore, in the bitterness-reducing agent of the present invention, phosphatidic acid or lysophosphatidic acid is used. It is preferable to use phosphatidic acid. The phosphatidic acid or lysophosphatidic acid is preferably present in the lipid mixture in an amount of at least 5% by weight, more preferably at least 20% by weight, particularly preferably at least 50% by weight.

The lipid mixture usually contains other lipid components in addition to the acidic phospholipid or its lyso form. Examples of lipid components other than acidic phospholipids and their lyso forms include neutral phospholipids (eg, phosphatidylcholine, phosphatidylethanolamine, and lyso forms thereof), neutral lipids (eg, triglyceride, diglyceride, monoglyceride), fatty acids , Sterol lipids, and glycolipids.

Investigations by the present inventors have revealed that reducing the amount of neutral lipids and neutral phospholipids in a lipid mixture can further enhance the bitterness reducing effect. Therefore, when a lipid mixture is used as the bitterness reducing agent of the present invention, the amount of neutral lipid present in the lipid mixture is preferably 30% by weight or less, more preferably 25% by weight or less, and particularly preferably 20% by weight or less. % By weight or less. The amount of the neutral phospholipid in the lipid mixture is preferably 50% by weight or less, more preferably 30% by weight or less, and particularly preferably 10% by weight or less. Further, the ratio of the neutral phospholipid to the acidic phospholipid or its lyso form in the lipid mixture is preferably not more than twice (neutral phospholipid / acidic phospholipid and its lyso form), more preferably 1 or less. / 2 or less, especially 1/5 or less, most preferably 1/50 or less. In addition, in order to increase the abundance of the acidic phospholipid and its lyso form in the lipid mixture, and to reduce the abundance of the neutral lipid, the lipid mixture containing these components is enzymatically decomposed,
After the solvent fractionation treatment, a method of performing a treatment such as an acetone treatment and a membrane separation can be used.

The bitterness reducing agent of the present invention may be made into a solid such as powder, granule, troche or the like, or a liquid such as paste or syrup, according to a known preparation method depending on the conditions used. it can. In addition, it is preferable to add an antioxidant to the bitterness reducing agent of the present invention in order to prevent and stabilize oxidation. Preferred antioxidants include, for example, tocopherol and polyphenol.

The method for reducing bitterness of the present invention can be carried out by adding a bitterness reducing agent to a substance having bitterness. When the substance having a bitter taste is a liquid such as an aqueous solution, a suspension, or an emulsion, an acid phospholipid such as phosphatidic acid or lysophosphatidic acid or a lyso form thereof usually has a bitter taste in the liquid. 0.01 to 100 parts by weight, preferably 0.1 to 20 parts by weight, based on 100 parts by weight of the total amount of the substance
Add by weight. When the substance having a bitter taste is a paste or solid, usually a phosphatidic acid, an acidic phospholipid such as lysophosphatidic acid or a lyso form thereof,
0.01 parts by weight or more (preferably 0.1 to 20 parts by weight) based on 100 parts by weight of the total amount of the paste or solid.
Added. In foods, pharmaceuticals, cosmetics, and the like to which a bitterness reducing agent is added by the bitterness reduction method of the present invention, the bitterness is specifically suppressed without suppressing the taste of other taste components.

Next, the objects to which the bitterness reducing agent of the present invention is added will be described in detail. The method for reducing bitterness of the present invention can be preferably applied to foods (including beverages) having bitterness, pharmaceuticals, or cosmetics. The form of food, medicine, or cosmetics having bitterness to be applied (hereinafter, sometimes simply referred to as food etc.) may be in the form of a liquid or paste such as an aqueous solution, a suspension, an emulsion, or a solid such as a powder. But it is good. When these forms are in the form of a liquid or paste such as an aqueous solution, suspension, or emulsion, the acidic phospholipid of the present invention or its lyso form (or a lipid mixture containing them) is added. Stirring well,
A dispersing method can be used. For the stirring and dispersion, a homogenizer, an emulsifier, an ultrasonic treatment device or the like can be used. The obtained dispersion may be dried, for example, by spray-drying or freeze-drying, and then into a solid such as powder or granules. When the form of food, medicine, or cosmetics having bitterness is a solid such as powder, a method of simply adding and mixing the acidic phospholipid of the present invention or its lyso form (or a lipid mixture containing them) is used. can do. In addition, acidic phospholipid or its lyso form (or
A lipid mixture containing them may be dispersed in water or the like, and this may be mixed with a food having a bitter taste in the form of a solid, mixed, homogenized, and then dehydrated. In addition, when the food or the like having the bitter taste has a bitter component that is hardly soluble in water, an organic solvent such as hexane or an alcohol such as ethanol is used, and after dissolving these components according to the present invention. Phospholipids can also be added.

When using the bitterness reducing agent of the present invention,
For example, as an aqueous solution, a method of preliminarily including this in the oral cavity and thereafter ingesting a food or drug having a bitter taste orally can be used.

Examples of foods (including beverages) having bitterness to which the bitterness reducing agent of the present invention is applied include the following. Citrus such as grapefruit, orange, lemon and fruit juice containing them; tomato,
Vegetables such as peppers, celery, cucumber, carrots, potatoes, asparagus and vegetable juices and vegetable juices containing them; sauces, soy sauce, miso, umami seasonings and peppers, etc .; soybean foods such as soy milk, soy milk; cream Emulsified foods such as garlic, dressing, mayonnaise and margarine; Fish processed foods such as fish meat, surimi and fish eggs; Nuts such as peanuts; Fermented products such as natto; Meats and processed meat products; Beer, coffee, cocoa, black tea, green tea , Fermented tea, semi-fermented tea, soft drinks, and functional beverages; pickles; noodles; soups including powdered soup; dairy products such as cheese and milk; bread and cakes; snacks, chewing gum, chocolate Candy; health foods; In addition, the bitterness of the food can be reduced by adding the flavor reducing agent of the present invention to the flavor used in the food in advance and then adding the flavor to the food. Furthermore, it can also be used to reduce the bitterness of amino acids, peptides, and oligosaccharides having bitterness such as leucine, isoleucine, and phenylalanine. further,
It can also be used to reduce the bitterness of tobacco.

When the bitterness reducing agent of the present invention is added to a food, the active ingredient (acidic phospholipid or its lyso form) is usually used in an amount of 0.05 to 3 based on the total amount of the food.
0% by weight, preferably 0.1 to 20% by weight, more preferably 0.5 to 15% by weight, particularly preferably 1 to 10% by weight, and most preferably 1 to 5% by weight.

Next, examples of drugs having a bitter taste include drugs having various bitter tastes conventionally used as drugs. In particular, basic drugs (for example,
Strychnine, quinine, papaverine, berberine,
It is effective in reducing the bitterness of acid addition salts of bromethazine, brucine, propranolol, chlorpromazine and the like. Examples of acid addition salts include mineral and organic acid salts such as hydrochloride, nitrate, sulfate, acetate, citrate, carbonate and the like.

The dosage form of the drug to which the bitterness reducing agent of the present invention is added is not particularly limited, and various dosage forms can be used. For example, solid preparations such as capsules, granules, pills, powders, tablets, troches and dry syrups, liquids, extracts, elixirs, alcoholic beverages, syrups, fragrances, limonades, fluid extracts, etc. Liquid preparations.

In formulating a pharmaceutical containing the bitterness reducing agent of the present invention, a known method can be used. Therefore, at the time of formulation, one or more conventionally used additives can be used in combination. Additives include, for example, excipients, binders, disintegrants, lubricants, glidants, coatings, flavoring agents, masking agents, fragrances, and antioxidants. Examples of the granulator used in the formulation process include a planetary mixer, a stirring granulator, a high-speed mixing granulator, an extrusion granulator, a fluidized bed granulator, a centrifugal tumbling fluidized granulator, and a roller compactor. And the like.

In the present invention, a bitterness reducing agent is used as the active ingredient (acidic phospholipid or lyso-form thereof) of the drug in an amount of usually 0.01 to 6 based on the total amount of the drug.
0% by weight (preferably 0.01 to 50% by weight, more preferably 0.1 to 30% by weight, particularly preferably 0.5 to 2% by weight).
0 wt%, and most preferably 1-10 wt%).

When the main ingredient, which is a medicinal ingredient of a drug, has a bitter taste, it is generally 0.01 to 1000 parts by weight (preferably 0.1 to 1 part by weight) per 1 part by weight of the main ingredient.
(00 parts by weight), the bitterness reducing agent of the present invention is preferably added. When two or more medicinal components having a bitter taste are present in a drug, the total weight is 1 part by weight.

Next, examples of cosmetics having a bitter taste include:
Cosmetics used for the face and cosmetics used for the oral cavity are included. Examples of cosmetics used on the face include lotions, emulsions, creams, packs, lipsticks, foundations, shaving aids, aftershave lotions, cleansing foams and cleansing gels. In addition, as cosmetics used for the oral cavity,
For example, toothpaste, mouthwash, and mouth rinse can be mentioned. Examples of the component exhibiting a bitter taste in cosmetics having such a bitter taste include surfactants such as sodium alkyl sulfate and sodium monoalkyl phosphate, menthol, linalool, phenylethyl alcohol, ethyl propionate, geraniol, linalool acetate. , Fragrances such as benzyl acetate, fungicides such as methylparaben, propylparaben, butylparaben,
Examples include humectants such as lactic acid and sodium lactate, alcohol denaturants such as 8-acetylated sucrose and brucine, and astringents such as aluminum lactate.

For cosmetics having a bitter taste, the agent for reducing bitterness of the present invention, as its active ingredient (acidic phospholipid or lyso-form thereof), is usually contained in an amount of 0.1% based on the total amount of the cosmetic.
05 to 30% by weight (preferably 0.1 to 20% by weight, more preferably 0.5 to 15% by weight, particularly preferably 1 to
10% by weight, and most preferably 1-5% by weight). In addition, it is preferable to use 0.1-1000 weight (especially 1-200 weight) of acidic phospholipid or its lyso form with respect to 1 weight part of components with respect to the quantity of the component which shows a bitter taste in cosmetics. .

[0036]

The present invention will be described more specifically below with reference to examples and comparative examples. In the following, "part"
Indicates "parts by weight" and "%" indicates "% by weight".

[Preparation of Bitter Taste Reducing Agent Sample Containing Acidic Phospholipid of the Present Invention and Its Lyso Form] (Preparation of Sample 1) 500 mL capacity 4 equipped with a stirring device
A commercially available defatted lecithin (trade name: SLPW-
SP, manufactured by True Lecithin Industry Co., Ltd.)
125 mL of 0.1 M Tris / HCl buffer (pH 6-8)
Hexane / ethyl acetate (2/1, V / V)
340 mL was added and stirred. Further, 150 mL of an aqueous calcium chloride solution (1M concentration) was added thereto, and then phospholipase D (derived from Streptomyces Chromofuscus, manufactured by Asahi Kasei Kogyo Co., Ltd.) of microbial origin was added to a 1 unit aqueous solution of 15 units.
50 mL was added, and stirring was continued for 14 hours while maintaining the temperature of the mixture at 30 ° C. to carry out the reaction. After the reaction, the reaction product was allowed to stand, and the solvent layer was separated. The solvent layer was taken out, and the solvent was distilled off under reduced pressure. Analysis of the lipid mixture component in the residue was performed using a thin-layer silica gel plate (Kieselgel: manufactured by Merck), and detection was performed using sulfuric acid coloring.
Table 1 shows the results.

(Preparation of Sample 2) 500 equipped with a stirrer
In a 4-mL flask having a capacity of 0 mL, 150 g of commercially available phosphatidylcholine (trade name: Epichlor S200, manufactured by Lucas Meier) was placed, and hexane / ethyl acetate (2/1,
(V / V) After adding 1500 mL, the mixture was stirred and dissolved therein. To this is added microbial phospholipase D (Streptom
yces Chromofuscus (from Asahi Kasei Kogyo)
After adding 1500 mL of an acetate buffer (pH 8) containing 0 units, 100 g of calcium chloride was added, and the reaction was carried out for 36 hours with stirring while maintaining the temperature at 37 ° C. After completion of the reaction, the solvent layer was separated, and the solvent was removed under reduced pressure to obtain about 100 g of a lipid mixture as a residue. The analysis of the lipid mixture components was similarly performed using a thin-layer silica gel plate, and detected using sulfuric acid coloring. Table 1 shows the results.

(Preparation of Sample 3) 25 g of US soybean (silky bean) was mixed with 0.1 M of 50 mM calcium chloride.
This was added to 150 g of an acetate buffer (pH 6), wet-pulverized at room temperature, and centrifuged (3000 rpm, 10 minutes) to obtain 120 g of a supernatant (extract). The obtained extract was used for preparing the following lipid mixture.

A commercially available defatted lecithin (trade name: SLPW-S) was placed in a 500 mL four-necked flask equipped with a stirrer.
P, manufactured by True Lecithin Industry Co., Ltd.), and 120 g of the extract from the soybean crushed material prepared above was added.
Ethyl acetate (250 mL) was added to the mixture while stirring.
, And 32.5 g of water are further added.
The mixture was stirred for an hour to react. The ethyl acetate layer was separated from the reaction product, and the remaining aqueous layer was extracted twice with chloroform / methanol (2/1, V / V), and the extract was subjected to Forti partition. Separately, ethyl acetate was removed from the ethyl acetate layer to obtain a residue. After combining these, chloroform / methanol was removed to obtain 22 g of a lipid mixture as a product. The analysis of the obtained lipid mixture component was similarly performed using a thin-layer silica gel plate, and detection was performed by sulfuric acid coloring. Table 1 shows the results.

[0041]

Table 1 Table 1 成分 Ingredients in lipid mixture Sample 1 ( %) Sample 2 (%) Sample 3 (%) ──────────────────────────────────── (Medium (Phospholipid) PC 000 PE 000 (Acid Phospholipid) PI 7.800 PA 54.2 94.0 62.0 PS 0.10 0.1 L-PA 0.5 1.0 0.9 << neutral lipid 18.4 4.0 18.0 glycolipid 19.0 1.0 19.0 >> ────────────────────────────────── PC: Phospha Phosphatidylcholine PE: phosphatidylethanolamine PI: phosphatidylinositol PA: phosphatidic acid PS: phosphatidylserine L-PA: lysophosphatidic acid

[Example 1] Grapefruit juice, orange juice and vegetable juice were selected as foods to be added. To these foods, the bitterness reducing agent sample 2 obtained above was added so that the final concentration was 0.1% (weight ratio) or 0.3% (weight ratio), and after stirring, each sample 2 was added. Was evaluated for its effect. The evaluation of the addition effect was 2
The sensory evaluation was performed by a panel of 10 test subjects of males and females in their 0s to 40s, and evaluated based on the following five criteria. Table 2 shows the evaluation results as average values. Bitterness intensity 5: Strong bitterness is felt. Bitterness intensity 4: Not strong, but bitter. Bitterness intensity 3: Slightly bitter. Bitterness intensity 2: Bitterness is felt to the extent that it can be perceived. Bitterness intensity 1: No bitterness is felt. Further, as control samples, foods to which no sample 2 was added were prepared, and their bitterness was evaluated in the same manner.

[0043]

[Table 2] Table 2 ──────────────────────────────────── Sample bitterness intensity (average value) ─ ─────────────────────────────────── Grapefruit juice 4.2 0.1% of sample 2 in grapefruit juice 2.2 grapefruit juice with 0.3% of sample 2 added ──────── Orange juice 3.8 Orange juice with 0.1% of sample 2 added 1.8 Orange juice with 0.3% of sample 2 added 1.0 ───── ─────────────────────────────── Vegetable juice 4.2 Vegetable juice with 0.1% of sample 2 added 2 .8 Vegetables 2.0% with sample 2 added to 0.3% ──

The results in Table 2 show that the addition of bitterness reducing agent sample 2 according to the present invention can significantly reduce bitterness.

[Example 2] Coffee (instant coffee and regular coffee) as a food to be added
And the intensity of bitterness was evaluated in the same manner as in Example 1 except that the bitterness reducing agent sample 3 was used. In addition, as a control example, coffee to which sample 3 was not added was prepared, and the bitterness intensity of each was evaluated in the same manner. The results are shown in Table 3 below.

[0046]

[Table 3] Table 3 物 Evaluation target bitterness intensity (average value) ──────────────────────────────────── イ ン ス タ ン ト Instant coffee 4.3 Instant coffee with sample 3 1% added 1.8 Instant coffee added 0.3% of sample 3 1.3 ────────────────────────── ────────── Regular coffee 4.8 0.1% sample 3 added to regular coffee 2.2 0.3% sample 3 added to regular coffee 1.0─── ───────────────────────────────── Note: Addition amount is based on beverage

From the results in Table 3, it was confirmed that the bitterness of coffee can be significantly reduced by adding Sample 3 according to the present invention. In addition, the taste became mild, and coffee that was easy to drink was obtained.

[Example 3] Powdered soup was selected as a food to be added, and 0.1% by weight or 0.3% by weight of a bitterness reducing agent sample 1 was added to this solution, followed by eating and drinking. In each case, the bitterness was reduced, the body taste was further increased, and the soup was good in flavor.

Example 4 As a drug to be added, propranolol having strong bitterness was selected, and its aqueous solution (1
0 mM), the final concentration of the bitter taste reducing agent sample 2 was set to 0.
Liquid preparations were added so as to be 3% (W / V) or 1.0% (W / V). For comparison, a liquid preparation was prepared by adding sucrose or sorbitol to the above-mentioned aqueous solution of propranolol (10 mM) so that the final concentration was 15% (W / V). The strength of bitterness of each of the obtained liquid preparations was evaluated by selecting 10 to 15 healthy male and female persons having normal taste and using them as subjects, and using the following equivalent concentration test method by the panel.

(Equivalent Concentration Test Method)
A reference liquid is prepared in advance so that the intensity of bitterness is evenly spaced, and the reference liquid and the liquid preparation prepared above are compared by subject's sensory evaluation, and the corresponding bitterness intensity is averaged. It is a method represented by. Here, as the reference solution, a solution prepared by adjusting the intensity of bitterness to 10 levels using quinine sulfate, which is a typical bitter substance, was used. Note that the intensity of the sensation such as the taste is proportional to the logarithm of the density, so that the density interval is not constant, but the intensity of the bitterness felt is equal.キ Quinine sulphate Quinine sulphate Bitterness intensity Concentration (g / 100mL) Bitterness intensity Concentration (g / 100mL) １ 1 0.00022 6 0.0037 2 0.00048 7 0.0058 3 0.0009 8 0.0094 4 0.0015 9 0.015 5 0.0023 10 0.0245 ────────────────── ────────────────── The evaluation results are shown in Table 4 below.

[0051]

[Table 4] Table 4 ──────────────────────────────────── Evaluation target bitterness intensity (average value) ──────────────────────────────────── ──────────────────────────────────── Propranolol aqueous solution 9.4 Bitter taste reducing agent sample in the above aqueous solution 5.6 No. 2 added 0.3% Bitter taste reducing agent sample 2 added to the above aqueous solution 1.0% 4.3%も の 15.0% sucrose added to the above aqueous solution 6.9 9.8% sorbitol added to the above aqueous solution 15.0% ──────────────────────────────────

From the results shown in Table 4, it can be seen that the addition of the bitterness reducing sample 2 according to the present invention can significantly reduce the bitterness of the drug.

Example 5 Instead of propranolol, liquid preparations were prepared in the same manner as in Example 4, except that the following drug was added with bitterness reducing agent sample 2. The bitterness intensity of each of the obtained liquid preparations was evaluated by the same evaluation method as described above. As a result, each liquid preparation had disappeared its inherent unpleasant bitterness, and became a liquid preparation that could be easily taken. Drugs used: quinine, promethazine, papaverine,
Chlorpromazine, berberine, brucine, strychnine

Example 6 Granules having the following composition were produced by extrusion granulation. Quinine hydrochloride (main drug component) 1 part Gelatinized starch 7 parts Corn starch 32 parts Lactose 55 parts Bitter taste reducing agent sample 3 5 parts As a control, the lactose content was increased to 60 parts without adding the bitter taste reducing agent sample 3 in the above composition. In the same manner, granules having the above composition and granules having a composition using lecithin (phosphatidylcholine) instead of the bitterness reducing agent sample 3 in the above composition were prepared as comparative examples. The bitterness intensity of each of the obtained granules was evaluated using the same method as in Example 4 (equivalent concentration test method). Table 5 shows the results.

[0055]

[Table 5] Table 5 ──────────────────────────────────── Evaluation target bitterness intensity (average value) ) 対 照 Control 8.4 Contains bitter taste reducing agent sample 3. Granules 4.5 Granules containing lecithin 7.8────────────────────────────────────

From the results shown in Table 5, it can be seen that bitterness can be significantly reduced by adding the bitterness reducing agent sample 3 according to the present invention.

Example 7 The intensity of bitterness was evaluated in the same manner as in Example 6 except that quinine hydrochloride as the main drug was replaced with the following drugs having bitterness. As a result, it was found that bitterness was significantly reduced for all drugs. Drugs used: promethazine, chlorpromazine, papaverine, propranolol, berberine

Example 8 A granule having the following composition was produced by extrusion granulation. Quinine hydrochloride (main drug component) 10 parts Gelatinized starch 10 parts Corn starch 25 parts Lactose 35 parts Bitter taste reducing agent sample 2 20 parts As a control, the lactose content was reduced to 55 parts without adding the bitter taste reducing agent sample 2 in the above composition. In the same manner, a granule having the above composition and a granule having a composition using lecithin (phosphatidylcholine) instead of the bitterness reducing agent sample 2 in the above composition were prepared as comparative examples. The bitterness intensity of each of the obtained granules was evaluated using the same method as in Example 4. Table 6 shows the results.

[0059]

[Table 6] Table 6 ──────────────────────────────────── Evaluation target bitterness intensity (average value) ) ──────────────────────────────────── Control 9.9 Contains bitter taste reducing agent sample 2. Granules 5.5 Granules containing lecithin 9.7 ────────────────────────────────────

The results in Table 6 show that the use of bitterness reducing agent sample 2 according to the present invention can significantly reduce bitterness.

Example 9 The intensity of bitterness was evaluated in the same manner as in Example 8 except that quinine hydrochloride, which was the main drug of Example 8, was replaced with the following drugs having bitterness. As a result, it was confirmed that bitterness was significantly reduced for all drugs. Drugs used: promethazine, chlorpromazine, papaverine, propranolol, berberine

Example 10 Tablets having the same composition as the granules prepared in Examples 8 and 9 were prepared. In addition, tablets having a combination of promethazine, chlorpromazine, papaverine, propranolol, and berberine instead of quinine hydrochloride (main drug component) were prepared in the same manner. The intensity of bitterness was evaluated for each tablet in the same manner as in Example 4. As a result, it was confirmed that the bitterness was significantly reduced in each case.

Example 11 A granule having the following composition was produced by a tumbling granulation method. Quinine hydrochloride (main drug component) 1 part Corn starch 35 parts Mannitol 58 parts HPC 3.5 parts (hydroxypropylcellulose) Bitter taste reducing agent sample 2 1 part Also, as a control, the bitter taste reducing agent sample 2 was not added in the above composition. Granules having a composition with a mannitol content of 59 parts,
And as a comparative example, granules having a composition using lecithin (phosphatidylcholine) in place of the bitterness reducing agent sample 2 in the above composition were prepared in the same manner. The bitterness intensity of each of the obtained granules was evaluated in the same manner as in Example 4.
Table 7 shows the results.

[0064]

[Table 7] Table 7 ──────────────────────────────────── Evaluation target bitterness intensity (average value) ) ──────────────────────────────────── Control 8.1 Contains bitter taste reducing agent sample 2. Granules 4.8 Granules containing lecithin 7.5

From the results in Table 7, it can be seen that the use of the bitterness reducing agent sample 2 according to the present invention can significantly reduce bitterness.

[Embodiment 12] In the above embodiment 11,
Example 11 except that the composition of the granules was changed as follows:
A granule was prepared using the tumbling granulation method in the same manner as described above. Quinine hydrochloride (main drug component) 10 parts Corn starch 25 parts Mannitol 50 parts HPC 5 parts (hydroxypropylcellulose) Bitter taste reducing agent sample 3 10 parts In addition, as a control, the mannitol content was not added without adding the bitter taste reducing agent sample 3 in the above composition. Granules having a blending ratio of 60 parts and, as a comparative example, granules having a composition using lecithin (phosphatidylcholine) instead of the bitterness reducing agent sample 3 in the above composition were prepared in the same manner. The bitterness intensity of each of the obtained granules was evaluated using the same method as in Example 4. Table 8 shows the results.

[0067]

[Table 8] Table 8 対 象 Evaluation target bitterness intensity (average value) ) ──────────────────────────────────── Control 9.5 Contains bitter taste reducing agent sample 3. Granules 5.6 Granules containing lecithin 9.2

From the results shown in Table 8, it can be seen that the use of the bitterness reducing agent sample 3 according to the present invention can significantly reduce bitterness.

Example 13 A syrup was prepared by the following method. To 100 mL of purified water, add 40 mg of butyl paraoxybenzoate, heat and dissolve.
g was added and stirred to homogenize. After cooling, promethazine was added to the obtained aqueous solution to a final concentration of 5 mM, followed by stirring and homogenization. Thereafter, the bitterness reducing agent sample 1 according to the present invention was further added to a final concentration of 1.0%, stirred and homogenized, and purified water was added to bring the total amount to 360.
to mL. In addition, in the preparation of the above syrup preparations, those without the bitterness reducing agent sample 1 were added as controls, and those with lecithin added instead of the bitterness reducing agent sample 1 as comparative examples. The bitterness intensity of each syrup obtained was evaluated using the same method as in Example 4. Table 9 shows the results.

[0070]

[Table 9] Table 9 ──────────────────────────────────── Evaluation target bitterness intensity (average value) ) ──────────────────────────────────── Control 7.9 Bitter taste reducing agent sample 1 was added Syrup 3.8 Syrup containing lecithin 6.9９

From the results shown in Table 9, it was confirmed that the bitterness can be remarkably reduced also by adding the bitterness reducing agent sample 1 according to the present invention to a drug in the form of a syrup.

Example 14 Sensory evaluation was performed using 1 mM quinine hydrochloride as a bitter substance. As the evaluation target, those to which phosphatidic acid was added, those to which phosphatidic acid and ovalbumin were added, and those to which soybean lecithin was added, and those to which rapeseed oil and β-lactoglobulin were added as comparative control examples were used. Was. The sensory evaluation is 20
Performed by 15 males and females in their 40s and 40s, and quantified by the equivalent concentration test method. That is, the strength of the standard solution (1 mM quinine hydrochloride aqueous solution) was converted to 1.0, and the degree of bitterness suppression was determined from the average of relative values. Table 10 shows the results.

[0073]

[Table 10] ──────────────────────────────────── Evaluation object Sensory evaluation value of bitterness水溶液 1 mM quinine hydrochloride aqueous solution (standard solution) 1.00 ── ０．３ 0.3 part of phosphor 0.113 ± per 100 parts of the above standard solution 0.022 Addition and dispersion of thidic acid 0.3 part of phosphoric acid 0.097 ± 0.017 thidic acid was added to 100 parts of the liquid, and 0.7 part of ovalbumin was added, followed by dispersion. ──────────────────── ０．３ 0.3 part of soybean 0.994 ± 0.028 lecithin is added to 100 parts of the above standard solution and dispersed. ０．３ Add 0.3 part of rapeseed oil 0.992 ± 0.085 to 100 parts of the above standard solution, and add 0.7 part of β-lactoglobulin. Added and dispersed ────────────────────────────────────

[Example 15] Raw quinine hydrochloride powder 0.0
4 g was dissolved in 100 mL of deionized water, 3 g of phosphatidic acid was added thereto, and 3 g of lactose was further added, followed by stirring and homogenization with a homogenizer. The obtained emulsion was dehydrated with a freeze dryer to obtain quinine powder containing phosphatinic acid. The obtained quinine powder had almost no bitterness.

[Example 16] The final concentration of purified water was 3.0.
%, And then the mixture was stirred and dispersed. The obtained dispersion of the bitterness reducing agent sample 3 was contained in the oral cavity for about 10 seconds, and then the mouth was gargled so that the dispersion could sufficiently spread in the oral cavity. Thereafter, the dispersion is spit out and the drug (0.1.
A 5 mM quinine hydrochloride aqueous solution and a 50 mM caffeine aqueous solution) were contained in the mouth, and the bitterness was evaluated for each of them. Also, for comparison, water, 10% sucrose aqueous solution, and 3.
The case where a 0% lecithin dispersion was used was also evaluated independently. Evaluation was performed using the equivalent concentration test method as described above. Table 11 shows the results.

[0076]

[Table 11] Table 11-Bitterness intensity in mouth for 10 seconds (Average value) Substance with bitterness Dispersion (or water) ──────────────────────────────────── 0.5 mM hydrochloric acid Dispersion of bitterness reducing agent sample 3 5.9 aqueous quinine solution water 9.2 10% aqueous sucrose solution 9.1 3.0% lecithin dispersion 8.8 ──────────分散 Dispersion of 50 mM caffeine bitterness reducing agent sample 3 5.5 aqueous solution water 9.0 10% sucrose Aqueous solution 8.6 3.0% lecithin dispersion 8.1────────────────────────────────────

From the results in Table 11, it can be seen that bitterness can be remarkably reduced when the liquid containing the bitterness reducing agent sample 1 according to the present invention is previously contained in the mouth and then a substance having bitterness is contained in the mouth. Recognize.

Example 17 The glossopharyngeal nerve response generated by stimulating the frog tongue was measured to quantitatively evaluate the effect of reducing the bitter taste by phosphatidic acid and lysophosphatidic acid. The bitter response of the frog taste organ is characterized by a high similarity with respect to the bitter taste threshold with the result of a human sensory test. For this reason, it becomes a quantitative evaluation system of the bitterness reducing effect.

Under a urethane anesthesia, the frog was incised on the outside of the lower jaw to expose the hypopharyngeal nerve. After cutting the central side, the frog was contacted with a silver electrode. The electric signal (nerve impulse) generated during the bitter taste stimulus was amplified, integrated, and recorded on a pen recorder.
The intensity of bitterness was defined as the response immediately after stimulation. Stimulation of the tongue surface was performed at a flow rate of 1.5 mL / sec.
It was 0 mL. As a substance having a bitter taste, strychnine nitrate was used, and as shown in the following (1) to (6), a system to which various additives were added was evaluated.
The result is shown in FIG.

(1) 1 mM aqueous solution of strychnine nitrate (2) 0.85 part of phosphatidic acid was added to 100 parts of 1 mM aqueous solution of strychnine nitrate, followed by stirring and dispersion. (3) 0.85 parts of phosphatidic acid was added to 100 parts of a 1 mM aqueous solution of strychnine nitrate, and 2.15 parts of β-lactoglobulin was further added to enhance dispersibility, followed by stirring and dispersion. (4) A solution obtained by adding 0.85 part of lysophosphatidic acid to 100 parts of a 1 mM aqueous solution of strychnine nitrate, followed by stirring and dispersion. (5) 0.85 part of rapeseed oil was added to 100 parts of 1 mM aqueous solution of strychnine nitrate, and β was added to further increase dispersibility.
-A mixture obtained by adding 2.15 parts of lactoglobulin and then stirring and dispersing. (6) In 100 parts of a 1 mM aqueous solution of strychnine nitrate,
After adding 3.0 parts of soybean lecithin, the mixture was stirred and dispersed.

As is clear from FIG. 1, bitterness was reduced in (2), (3) and (4) to which the bitterness reducing agent of the present invention was added, but this is a comparative example. In (1), (5) and (6), reduction in bitterness was not observed.

[0082]

Industrial Applicability The bitter taste reducing agent according to the present invention exhibits an excellent bitter taste reducing effect, is safe for living bodies, and easily reduces bitter taste by using the bitter taste reducing agent of the present invention. Can be. Examples of the substance having a bitter taste to which the bitterness reducing agent of the present invention is added include various foods, pharmaceuticals, and cosmetics, and among foods, bitterness can be reduced without changing the taste. Becomes

[Brief description of the drawings]

FIG. 1 is a graph showing evaluation results of bitterness of strychnine using frogs. (1) is the standard value (control)
In the graph, (2) to (4) show the effects of the phosphatidic acid and lysophosphatidic acid according to the present invention, and (5) and (6) show comparative examples.

────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. ⁶ Identification number Agency reference number FI Technical display location A61K 47/24 A61K 47/24 L (72) Inventor Tomoki Mitsui 1 Ohnohara, Kamisu-cho, Kashima-gun, Ibaraki Prefecture -8

Claims (9)

(57) [Claims] 1. A bitterness reducing agent comprising an acidic phospholipid or a lyso form thereof as an active ingredient. 2. An acidic phospholipid or a lyso form thereof is present in a lipid mixture, and the neutral lipid in the lipid mixture is 3%.
The bitterness reducing agent according to claim 1, which is 0% by weight or less. 3. The method according to claim 1, wherein the acidic phospholipid or the lyso form thereof is present in the lipid mixture, and the amount of the acidic phospholipid or the lyso form thereof in the lipid mixture is 20% by weight or more. Bitter taste reducing agent. 4. The bitter taste reducing agent according to claim 1, which contains both an acidic phospholipid and a lyso form thereof. 5. An acidic phospholipid or a lyso form thereof is present in a lipid mixture, and an amount of a neutral phospholipid in the lipid mixture is not more than twice the content of the acidic phospholipid or a lyso form thereof. The bitterness reducing agent according to claim 1. 6. The bitter taste reducing agent according to claim 1, wherein the acidic phospholipid and its lyso form are phosphatidic acid and lysophosphatidic acid, respectively. 7. The bitterness reducing agent according to any one of claims 1 to 6 is added to a food having a bitter taste as an active ingredient in an amount of 0.05 to 30% by weight based on the total amount of the food. A method for reducing bitterness, characterized in that: 8. A pharmaceutical product having a bitter taste, wherein the pharmaceutical product has a bitter taste.
13. A method for reducing bitterness, comprising adding the bitterness reducing agent according to any one of the above items as an active ingredient in an amount of 0.01 to 60% by weight based on the total amount of the drug. 9. A cosmetic product having a bitter taste, wherein the cosmetic product has a bitter taste.
13. A method for reducing bitterness, which comprises adding the bitterness reducing agent according to any one of the above items as an active ingredient to the cosmetic in an amount of 0.05 to 30% by weight.