JP4947758B2 - Powdered composition of propolis extract and method for producing the same - Google Patents

Description

  The present invention relates to a propolis extract that can be used as a pharmaceutical, food-drinking, cosmetic, or oral composition, or a powdery composition containing a high extract of a plant of its origin, and a method for producing the same.

  Propolis is a substance that bees are constructed by mixing saliva with shoots, leaves, berries, and sap of plants such as Aleklin (Baccharis dracunculifolia). (Shigeta Tazawa et al., Natural Medicines 54 (6): 306-313, 2000: Non-Patent Document 1). A propolis extract extracted with alcohol or an aqueous alcohol solution is excellent in antibacterial properties and antioxidant activity, and has been used in folk remedies especially for cancer treatment and prevention.

  Propolis has different types and amounts of active ingredients depending on the place of production. However, propolis contains abundant fat-soluble active ingredients such as flavonoids, terpenoids and cinnamic acid (Non-patent Document 1). As a method for efficiently extracting these components, an edible alcohol such as ethanol or a mixture of alcohol and water is most widely used. However, since the propolis extract extracted with alcohol is liquid, it cannot be processed into soft capsule tablets, granule preparations, and hard capsule preparations. Alcohol extract with a propolis extract content of 70% or more (alcohol content of 30% or less) can be filled into soft capsules, but it can only contain up to about 50% of the capsule content.

  The propolis extract extracted with edible alcohol can be evaporated with hot air or freeze-dried to evaporate the alcohol to obtain a solid, but the resulting propolis extract is very sticky, so it becomes a fine powder. It is difficult to process. Propolis extract extracted with water containing organic solvent such as acetone, hexane, carbon dioxide in supercritical state, or compound having both hydrophilic and lipophilic properties (surfactant, glycerol, propylene glycol, polyethylene glycol) Similarly, it is difficult to form a powder by drying with hot air or freeze drying.

  As one method for solving these problems, a method of mixing dextrin or dietary fiber (JP-A-6-70705: Patent Document 1) as an excipient with a propolis extract extracted with edible alcohol has been used so far. It was. However, the content of the propolis extract of the powder obtained by this method is about 50% at the maximum, and at a concentration higher than that, there is a problem that it is solidified solidly at a high temperature of 25 ° C. or higher.

  As a method for obtaining a high-concentration powdery propolis extract, flaky starch hydrolyzate (JP-A-8-70797: Patent Document 2, JP-A-2000-350557: Patent Document 3), lactose (JP-A 2000-350557: Patent Document 3) or saponin (Japanese Patent Laid-Open No. 2001-10963: Patent Document 4) has been reported to be mixed with a propolis extract extracted with alcohol and dried. However, in order to obtain a flowable powder that can be filled into hard capsules by these methods, starch hydrolyzate or saponin must be added to the propolis extract at a concentration of 33.3% by weight or more. According to the examples described in the patent relating to the powder of the propolis extract composition to which starch hydrolyzate or saponin is added, the content of propolis extract in the composition in the case of adding starch hydrolyzate is at most 50 In the case of addition of saponin, the content of propolis extract in the composition is 66.7% by weight at the maximum. Thus, no powder of a propolis extract composition having a content of 70% by weight or more has been reported so far.

  Propolis extract compositions to which carbohydrates and saponins are added (when the propolis extract content is 50% or more) can be temporarily powdered, but they must be stored at 25 ° C or more for several months or more. If the powder particles adhere to each other and form an irreversible hard mass, they cannot be stored for a long time. In addition, when stored at a high temperature of 40 ° C., the particles are bonded to each other in a short period of time and become a hard rod-like lump, and thus cannot be stored at a high temperature from May to September in Japan. Usually, in order for a hard capsule or granular preparation filled with propolis extract to have stable physical properties for at least one year (when the expiration date is set to one year), the preparation is packaged at 40 ° C. It is desirable that it can be stored at high temperature for more than 2 months (Emiko Araki Journal of Japanese Society of Low Temperature Preservation 22 (4) 241-248, 1996: Non-Patent Document 2). However, no powdered propolis extract having stability to a high temperature of 40 ° C. has been reported so far in a composition having a propolis extract content of 50% by weight or more. Therefore, as a matter of course, 70% or more of the filled content is a propolis extract, and there was no hard capsule product having a high temperature resistance of 40 ° C. or more.

  In addition, it has been reported that tablets (tablet products) were produced using a propolis extract to which flaky starch hydrolyzate or lactose was added (Japanese Patent Laid-Open No. 2000-350557). The concentration of propolis extract contained in the tablet is a maximum of 15% by weight. It is unclear whether the tablet has sufficient hardness. Therefore, the hardness of the propolis extract is 15% or more, and the hardness is 3.5 kg or more that can withstand physical impact (the hardness required to withstand the impact that occurs during transportation and use as a product). No tablet has ever existed.

JP-A-6-70705 JP-A-8-70797 JP 2000-350557 A JP 2001-10963 A Tazawa Shigeru et al. Natural Medicines 54 (6): 306-313, 2000 Emiko Araki Journal of Japan Society of Low Temperature Food Storage 22 (4) 241-248, 1996

  An object of the present invention is to develop a high-temperature stable powdery composition containing a high amount of propolis extract extracted using alcohol or supercritical carbon dioxide and having high fluidity, and a capsule formulation using the composition , To provide tablets and granule preparations.

  In order to solve the above-mentioned problems, the present inventors have developed a propolis extract extracted with alcohol from amino acids that are safe and have no problem for use as foods, analogs thereof, and peptides to which they are bound. As a result of searching for compounds that can provide a high-flowability, high-temperature, stable powder composition when blended and mixed, then dried and ground, betaine, β-alanine, creatine, γ-aminobutyric acid, L-carnitine, L-carnosine, L-ornithine, L-theanine, pantothenic acid, L-arginine, L-lysine, L-histidine, L-proline, L-tryptophan, L-glutamic acid, poly-L-arginine, respectively The propolis extract powder obtained by freeze-drying after adding to the propolis extract at a ratio of about 50% or less is about Although there is a difference, the present inventors have found that it can be stably stored because it does not form a bowl-like lump under normal temperature and high temperature conditions. Furthermore, the structure of these amino acids and analogs thereof was analyzed to find a common mother nucleus structure, and the present invention was completed.

That is, the present invention relates to (1) a powdery composition of a propolis extract or a plant extract derived from propolis characterized by containing L-carnosine.

The present invention also relates to (2) a powdery composition of a propolis extract or a propolis-derived plant extract as described in (1) above, which contains less than 50% by weight of L-carnosine.

The present invention also relates to (3) a powdery composition of a propolis extract or a propolis-derived plant extract as described in (2) above, which contains less than 30% by weight of L-carnosine.

In addition, the present invention provides (4) any one of the above (1) to (3), wherein the plant extract of propolis is at least one selected from extracts of alectrine, eucalyptus, poplar and jujube It relates to a powdery composition of the described propolis extract or plant extract of propolis origin.

In the present invention, (5) the propolis extract or the propolis origin plant extract is an ethanol extract, hydrous ethanol extract, supercritical carbon dioxide extract, supercritical ethanol extract, supercritical water, or a propolis origin plant. It is an extract, It is related with the powdery composition of the propolis extract or the plant extract of propolis origin in any one of said (1)-(4) characterized by the above-mentioned.

Moreover, this invention contains the powdery composition of the propolis extract or propolis origin plant extract in any one of (6) said (1)-(5), The pharmaceutical use, food-drinks, and makeup | decoration characterized by the above-mentioned Or an oral composition.

The present invention also relates to (7) a capsule preparation, a granule preparation or a tablet comprising the powdery composition of the propolis extract or the plant extract of propolis origin according to any one of (1) to (6) above.

The present invention also relates to (8) a method for producing a powdery composition, wherein L-carnosine or a solution thereof is mixed and stirred in a propolis extract or a propolis-derived plant extract and then dried.

The present invention also provides (9) the powdery composition according to (8) above, wherein the plant extract of propolis is at least one selected from the extracts of alectrin, eucalyptus, poplar and jujube. It relates to a manufacturing method.

In the present invention, (10) the propolis extract or the propolis origin plant extract is an ethanol extract, hydrous ethanol extract, supercritical carbon dioxide extract, supercritical ethanol extract, supercritical water, or a propolis origin plant. (8) to (8) to (8), wherein the method is a method for producing a powdery composition according to (8) or (9) above, or (11) freeze drying or hot air drying. It relates to the manufacturing method of the powdery composition in any one of 10).

  According to the present invention, by providing a propolis extract powder containing an amino acid that has not been known so far, a high-concentration propolis extract-containing preparation having a high concentration of 50% by weight or more can be obtained. be able to.

As a powdery composition of the propolis extract or propolis origin plant extract of the present invention, a compound represented by any one of the following formulas (I) to (V) (a propolis extract or a propolis origin plant extract is powdered): A compound capable of pulverizing a propolis extract or a plant extract derived from propolis; hereinafter referred to as a “powdered weight”. In the formulas (I) to (V), R is a hydrogen atom, a substituted or unsubstituted lower alkanoyl group, an amidino group, or a carboxyl group. together with the methylene group adjacent to the group may form a ring, R ¹ and R ² may be the same or different, represents a single bond or a divalent organic group, R ³ is Imidazolyl group, an indolyl group or a N- diethylcarbamoylmethyl group. Here, the lower alkanoyl group represents a C1-C6 formyl group, acetyl group, propionyl group, butyryl group, valeryl group, hexanoyl group and their respective isomers. The same or different, a hydroxy group having 1 to 3 substituents and an amino group can be shown, and the divalent organic group represents a substituted or unsubstituted methylene group, an ethylene group or an amide group. The group represents an amino group, a hydroxy group, a carboxyl group or an imidazolylmethyl group. The powdered compounds represented by any of formulas (I) to (V) are exemplified in [Table 1].

R—NH—CH ₂ —CH ₂ —R ¹ —R ² —COOH (I)
R—NH—R ¹ —R ² —CH ₂ —CH ₂ —COOH (II)
R—NH—CH (CH ₂ —R ¹ —R ³ ) —COOH (III)
^{_{(CH 3) 3 N + -R}} 1 -R 2 -CH 2 -COO - (IV)
R—NH—C (NH) —N (CH ₃ ) —CH ₂ —COOH (V)

  As shown in Table 1, as powdered compounds, betaine, β-alanine, creatine, γ-aminobutyric acid, L-carnitine, L-carnosine, L-ornithine, L-theanine, pantothenic acid, L-arginine, L -Lysine, L-histidine, L-proline, L-tryptophan and L-glutamic acid can be preferably exemplified.

  Moreover, in this invention, the polymer which 1 or more types of the compound shown by either of formula (I)-(V) couple | bonded is the same or shown by either of formula (I)-(V), or This means a polymer in which two or more of different compounds are polymerized by an acid amide bond. Examples of such a powdered polymer include L and / or D polyarginine, polylysine, polyhistidine, polyornithine, and polyglutamic acid. Of these, poly-L-arginine can be preferably exemplified.

  The powdery composition of the propolis extract or propolis origin plant extract of the present invention is a powdery composition in which the propolis extract or propolis origin plant extract is mixed with the above powdered compound or powdered polymer. This powdery composition includes, for convenience, a solid before being pulverized into a powder. The extraction solvent for propolis extract and propolis origin plant extract is not particularly limited as long as it is a solvent capable of extracting a fat-soluble component, but edible alcohol such as ethanol, a mixed solution of the edible alcohol and water, acetone, Preferable examples are organic solvents such as hexane, water containing both hydrophilic and lipophilic compounds (surfactant, glycerol, propylene glycol, polyethylene glycol), supercritical carbon dioxide, alcohol, water, and the like. Among them, ethanol, hydrous ethanol, and supercritical carbon dioxide that can efficiently extract a fat-soluble component and are widely used as an extraction solvent throughout the world are particularly preferable.

  Propolis production areas used in the present invention can include Brazil, China, Australia, New Zealand, North America, etc., but are not particularly limited, and propolis origin plants may be propolis origin plants. Although it does not restrict | limit in particular, Aleklin, eucalyptus, poplar, and jujube can be illustrated suitably.

  In the powdered composition of the propolis extract or propolis origin plant extract of the present invention, the above powdered compound or powdered polymer is less than 50% by weight, that is, the propolis extract or propolis origin plant extract is 50% by weight. What is contained above is preferable, and in particular, the above powdered compound or powdered polymer is preferably less than 30% by weight, that is, a product containing 70% by weight or more of propolis extract or plant extract derived from propolis.

The powdery composition of the propolis extract or propolis-derived plant extract of the present invention is:
For example, liquid or pasty propolis extract extracted with ethanol, hydrous ethanol, supercritical carbon dioxide (supercritical method), etc. (preferred propolis extract concentration is 10 to 50%) or propolis origin plant extract (preferred propolis origin) The plant extract concentration is 10 to 50%), and the powdered compound or powdered polymer is directly added to the solution and stirred or dissolved or dispersed, followed by drying treatment such as freeze drying or hot air drying. It can manufacture by grind | pulverizing the obtained solid substance.

  When using a powdered compound or powdered polymer that is difficult to dissolve in ethanol, dissolve the powdered compound or powdered polymer in an aqueous solution having an ethanol concentration of 50% or less in advance, and then the powdered compound or powdered polymer. Can be added to the 50-70% by weight propolis extract with stirring and mixed. In addition, when using a powdered compound or powdered polymer that is difficult to dissolve in water, the above powdered compound or powdered polymer is added to an aqueous alcohol solution having a water concentration of 50% or less or an organic solvent such as ethanol, hexane, or acetone. Can be dissolved or dispersed in advance, and the powdered compound or powdered polymer solution can be added little by little to the 50-70 wt% propolis extract while stirring. Thereafter, freeze-drying or hot-air drying is performed, and the obtained solid is pulverized to obtain a powdery propolis extract composition or a propolis-derived plant extract composition.

  In addition, as a pharmaceutical, food-drinking, cosmetic, or oral composition containing the powdered composition of the propolis extract or propolis-derived plant extract of the present invention, a hard capsule preparation filled with the propolis extract at a high concentration, Pasty formulations, granule formulations, and tablets can be provided. When used as a pharmaceutical, cosmetic, or oral composition, conventional pharmaceutically acceptable carriers, binders, stabilizers, excipients, diluents, pH buffering agents, disintegrants, solubilizers Further, various compounding ingredients for preparation such as a solubilizing agent and an isotonic agent can be added. In addition, when used for food and drink, it can be eaten as capsules and tablets as it is, but various drinks such as yogurt, drink yogurt, juice, milk, soy milk, liquor, coffee, tea, sencha, oolong tea, sports drinks, Baked confectionery such as pudding, cookies, bread, cakes, jelly, rice crackers, Japanese confectionery such as sheep crab, bread and confectionery such as frozen confectionery, chewing gum, noodles such as udon and soba, fish paste products such as kamaboko, ham, and fish sausage To be used in seasonings such as yam, miso, soy sauce, dressing, mayonnaise, sweeteners, dairy products such as cheese and butter, tofu, konjac, other boiled fish, dumplings, croquettes and salads. You can also.

  Hereinafter, the present invention will be described in detail based on examples and comparative examples, but the technical scope of the present invention is not limited to these examples. In Examples, a method for pulverizing a propolis extract extracted with ethanol or supercritical carbon dioxide, which is an extraction solvent that can efficiently extract fat-soluble components and is widely used all over the world, will be described. Further, a capsule preparation filled with the propolis extract powder and a method for producing tablets will be described.

[Comparative Example 1]
(Stability test result of propolis extract composition containing starch hydrolyzate)
A propolis extract composition to which a starch hydrolyzate was added was prepared with reference to the examples of JP-A-8-70797 (Patent Document 1). Approximately 8.3 kg of Brazilian propolis extract with a concentration of 60% by weight extracted after extraction with ethanol and 5.0 kg of starch hydrolyzate (trade name Pine Flow manufactured by Matsutani Chemical Industry Co., Ltd.) are mixed and dried with hot air And dried at 50 ° C. for 24 hours. After cooling, the powder obtained by pulverization was collected with a mesh 30 to obtain a powdered propolis extract having a concentration of 50% by weight. The recovery rate of this extract was very low due to many losses in fractional collection.

  In the same procedure, a propolis extract having a starch hydrolyzate content of 30% by weight was obtained by hot air drying or freeze drying (at -20 ° C for 48 hours). As a comparative control, a Brazilian propolis extract having a concentration of 60% by weight was directly dried with hot air or freeze-dried to obtain a solid propolis extract.

  A propolis extract containing 30% by weight of a starch hydrolyzate was sticky regardless of the drying temperature during the production process, so that a fluid powder could not be obtained. Therefore, it did not reach the stage which performs a stability test (refer Table 2).

Therefore, the stability test and the acceleration test were carried out only for the powdered propolis extract having a concentration of 50% by weight. First, 1 g of desiccant was added to 10 g of the extract and hermetically packaged in a vinyl bag. For the stability test, these specimens were treated for 2 months in a constant temperature layer at a temperature of 20 ° C. and a humidity of 60% (RH), and for the acceleration test, the sample was conducted for 2 months at a temperature of 40 ° C. and a humidity of 75% (RH). . Thereafter, the state of the powder was visually observed, and its shape and fluidity were evaluated in five stages from A to E as follows. The results are shown in [Table 2].
A: The particles did not adhere to each other and were powdery.
B: The particles partially adhered to each other to form a soft lump, but when loosened, the particles returned to the original powder form.
C: Particles partially adhered to each other to form a lump, but could be re-powdered by grinding.
D: A bowl-shaped lump in which particles were firmly attached to each other was formed.
E: The stability test was not carried out because it was already sticky immediately after drying in the production process and could not be pulverized by physical pulverization.

  The propolis extract powder containing 50% by weight of starch hydrolyzate was stored at 25 ° C. for 2 months. As a result, the powder particles adhered to each other and became an irreversible hard mass. Further, when stored at a high temperature of 40 ° C., the particles were bonded to each other within one month to form a hard rod-like lump. From the above results, propolis extract powders containing 30-50% by weight of these starch hydrolysates are highly likely to deteriorate in Japan at high temperatures from May to September, such as hard capsules and granules. It is thought that it cannot be used for other preparations.

[Comparative Example 2]
(Results of stability test of propolis extract composition containing saponin)
The Brazilian propolis extract composition to which extracted ginseng saponin was added was hot-air dried (at 50 ° C. for 24 hours) with reference to the examples of JP-A-2001-10963 (Patent Document 2), and 66.7 wt. % Propolis extract powder was made. However, it was highly viscous and could not be crushed. On the other hand, a 66.7% by weight propolis extract was similarly produced by changing the drying method to freeze-drying, and pulverized using a mortar. The results of the stability test and the acceleration test according to Comparative Example 1 are shown in [Table 3]. As a result, the stability test and the acceleration test were in the evaluation D state. Therefore, it became clear that these are not the quality which can be put into practical use.

(Stability test results of Brazilian propolis extract composition)
The Brazilian propolis extract extracted with 99.5 wt% ethanol was concentrated to 70 wt% concentration with an evaporator to obtain a highly viscous propolis extract concentrate. Next, various amino acids (taurine, betaine, L-alanine, β-alanine, creatine, γ-aminobutyric acid, L-carnitine, L-carnosine, L-theanine, pantothenic acid, L-arginine, L-lysine, L -Histidine, L-proline, L-tryptophan, L-aspartic acid, L-glutamic acid, L-asparagine, L-glutamine, L-tyrosine, L-valine, L-leucine, L-isoleucine, L-methionine, L- (4.8 g of phenylalanine, L-glycine, L-serine, L-threonine, L-cysteine) were each dissolved or mixed and dispersed in 12 g of a 50 wt% aqueous ethanol solution. An aqueous ethanol solution in which various amino acids were dissolved in 16 g of a 70 wt% propolis extract was added little by little with stirring and stirred for 12 hours to obtain an aqueous ethanol solution in which the propolis extract and amino acid were uniformly mixed. This was freeze-dried at −20 ° C., and the resulting solid was pulverized and collected with a mesh 30. The content of the obtained propolis extract was 70% by weight, and the content of the additive was 30% by weight. With respect to these specimens, the stability test, the acceleration test, and the specimen evaluation were performed according to Comparative Example 1. The results are shown in [Table 4].

  As a result of the stability test, β-alanine, γ-aminobutyric acid, L-carnitine, L-carnosine, L-theanine, pantothenic acid, L-arginine, L-lysine, L-histidine, L-proline, L-tryptophan, The propolis extract powder containing L-aspartic acid, L-glutamic acid, L-asparagine and L-glutamine maintained a certain fluid powder state. However, many of the accelerated tests were relatively hardened and wrinkled. In order to maintain a quality that does not cause a significant problem in appearance when filled into a hard capsule preparation, the result of the accelerated test must be C or higher. Therefore, the addition of β-alanine, γ-aminobutyric acid, L-carnosine, L-theanine, pantothenic acid, L-arginine, L-lysine, L-histidine, L-proline, and L-tryptophan is a powdered propolis extract. It can be said that this is an effective method. Among them, L-carnosine, pantothenic acid, and L-arginine were in a very good storage state with almost no change in color, shape, and fluidity before and after the acceleration test.

(Results of stability test of Chinese propolis extract powder)
A highly viscous propolis extract solution having a concentration of 70% by weight was obtained from a Chinese propolis extract solution extracted with 99.5% by weight ethanol. In the same manner as in Example 3, a stability test and an acceleration test were carried out using a powdered propolis extract with a concentration of 70% by weight (additive content was 30% by weight) blended with an amino acid and an analog thereof. The fluidity of the specimen was evaluated according to Comparative Example 1. The results are shown in [Table 5].

  When a 70% by weight Chinese propolis extract containing no additive was freeze-dried, a solid was obtained and pulverized. The state after the stability test was also at the C level, and a tendency to be pulverized more easily than Brazilian propolis was observed. Moreover, the fluidity of the powder was improved without exception by the addition of an amino acid or an analog thereof, and a remarkable improvement trend was observed after the stability test. However, specimens that obtained fluidity higher than C rank after the accelerated test were betaine, β-alanine, creatine, γ-aminobutyric acid, L-carnitine, L-carnosine, L-theanine, L-ornithine, pantothenic acid , L-arginine, L-lysine, L-histidine, L-proline, L-tryptophan, and L-glutamic acid. Among them, L-carnosine, pantothenic acid, and L-arginine have almost no change in color, shape, and fluidity before and after the accelerated test and are in a very good storage state, and have high commonality with Brazilian propolis results. there were.

  On the other hand, the effects of the addition of betaine, creatine, L-carnitine, L-ornithine, and L-glutamic acid were different from those of Brazilian propolis, and were effective in producing high temperature resistant powder in Chinese propolis.

In Tables 4 and 5, as a result of analyzing the structures of amino acids and analogs effective for pulverization of propolis extract, a common mother nucleus structure was found. The minimum unit compound is β-alanine (NH ₂ —CH ₂ —CH ₂ —COOH), and has an ethylene group between an amino group (NH ₂ —) and a carboxyl group (—COOH). Taurine having a carboxyl group of —SO ₃ H has a small effect, suggesting that the carboxyl group is essential. In addition, L-arginine and L-lysine are effective, whereas L-methionine and L-glutamine are ineffective. Therefore, an amino group is considered essential. However, since L-alanine is not effective and β-alanine is effective, it is considered that the amino group has no effect unless it is bonded to a carbon other than the α-position carbon to which the carboxyl group is bonded. . This assumption is also supported by the effect on L-tryptophan and histidine. Judging from the above, it is considered that certain amino acids represented by the following formula (I) or (II) and analogs thereof are effective.

R—NH—CH ₂ —CH ₂ —R ¹ —R ² —COOH (I)
R—NH—R ¹ —R ² —CH ₂ —CH ₂ —COOH (II)
R—NH—CH (CH ₂ —R ¹ —R ³ ) —COOH (III)

Betaine and L-carnitine were not very effective in accelerated tests for Brazilian propolis, but were effective in China. Therefore, in Chinese propolis pulverization, the amino group hydrogen atom of the additive was a methyl group. It is considered effective even if it is replaced by. Therefore, the compound represented by the following formula (IV) was considered to be effective for pulverization of Chinese propolis extract.
_{^{(CH 3) 3 N + -R}} 1 -R 2 -CH 2 -COO - (IV)
Further, since creatine was effective, it was considered that the compound represented by the formula (V) would be effective for pulverization of Chinese propolis extract.
R—NH—C (NH) —N (CH ₃ ) —CH ₂ —COOH (V)

(Results of stability test of propolis extract powder containing L-arginine)
Powdered propolis extracts having an arginine content of 10, 20, 30, 40, and 50% by weight were prepared in the same manner as in Example 1, and subjected to a stability test and an acceleration test. The fluidity of the specimen was evaluated according to Example 1. As a result, a powder having a content of 80% by weight of propolis extract in the Brazilian propolis extract and a content of 90% by weight of propolis extract in the case of the Chinese propolis extract was obtained. Even when the content of arginine was increased to 30% by weight or more, the fluidity was hardly affected.

(Filling test of L-arginine-containing propolis extract composition into hard capsule)
A powdery Brazilian propolis extract containing 30% by weight of arginine obtained by scaling up the production method of Example 3 was added to 10.2 kg of sucrose fatty acid ester (purchased from Daiichi Kogyo Seiyaku Co., Ltd.) 0.3 kg After mixing the mixture uniformly, it was poured into a powder filling machine (model name G37 / N manufactured by MG2 in Italy) equipped with No. 1 gelatin hard capsule (manufactured by Capsugel Japan Co., Ltd.), and the following prescription settings [Table 7 The capsule was filled.

  Of the produced capsules, 10 were randomly extracted and weighed. As a result, the average error was +4 mg and the maximum error was +11 mg [Table 8]. In addition, as a result of visual inspection of 2,000, no capsules that were insufficiently filled or whose contents were discolored or solidified were detected.

(Acceleration test of hard capsule of propolis extract composition containing L-arginine)
90 hard capsules of L-arginine-containing propolis extract composition prepared in Example 6 and 1 g of a desiccant were placed in a plastic container and sealed. It was stored in a constant temperature layer at 40 ° C. and a humidity of 75% RH for 4 months. The contents of the hard capsule were taken out before and after the accelerated test, respectively, and the content of p-coumaric acid was measured according to the guidance of the Japan Health and Nutrition Food Association. The results are shown in [Table 9]. Compared with before the test, p-coumaric acid after the acceleration treatment was hardly decomposed, and the residual ratio was 95.3% by weight. Alternatively, the fluidity of the contents of the capsule was sufficiently maintained even after the acceleration test. The result of evaluating the fluidity of the contents after the acceleration test according to Comparative Example 1 was A level.

(Production of tablets containing a propolis extract composition containing L-arginine)
A Brazilian propolis extract powder containing 30% by weight of L-arginine obtained in Example 3 was used to produce a circular tablet having a diameter of 8 mm using a tableting machine (model name LIB2 0836SS2JZ manufactured by Kikusui Seisakusho Co., Ltd.). did. The hardness of the obtained tablet was measured using a hardness meter (model name KHT-20N manufactured by Fujiwara Seisakusho Co., Ltd.). As a result, the hardness was 4.5 kg (3 specimens were measured, and the standard deviation was 0.10 kg). This hardness was sufficient to prevent the tablet from being deformed even when the tablet was filled in a glass container or packaged with PTP.

(Stability test results of propolis extract composition containing L-tryptophan)
Since the powdery propolis extract having a tryptophan content of 30% by weight is transformed into a C-rank state after the accelerated test, its relative effect is low (see Examples 3 and 4). Therefore, the L-tryptophan content was increased, and 40 and 50% by weight of a powdered propolis extract was produced by the same production method as in Example 3 and subjected to a stability test and an acceleration test. As a result, in both Brazilian propolis extract and Chinese propolis extract, the fluidity of the powdered propolis extract was improved depending on the L-tryptophan content (see Table 10). In the 50% by weight powdery propolis extract, B level fluidity was obtained after the accelerated test.

(Results of stability test of mixed composition of propolis extract and L-arginine obtained by supercritical carbon dioxide)
In the same manner as in Example 1, L-arginine was added to the propolis extract obtained with supercritical carbon dioxide, and the L-arginine content was adjusted to 30, 40, and 50% by weight. The specific work procedure is as follows. First, 4.8 g, 6.4 g, and 11.2 g of L-arginine were dissolved or mixed and dispersed in 12 g of 50% by weight ethanol aqueous solution. Ethanol aqueous solution with L-arginine dissolved in 11.2 g of Brazilian and Chinese propolis extracts obtained with supercritical carbon dioxide was added little by little, and stirred for 12 hours to mix the propolis extract and L-arginine uniformly. An ethanol aqueous solution was obtained. This was freeze-dried at −20 ° C., and the resulting solid was pulverized and collected with a mesh 30. A powdery propolis extract with an L-arginine content of 30, 40 and 50% by weight was thus obtained. With respect to these specimens, the stability test, the acceleration test, and the specimen evaluation were performed according to Comparative Example 1. The results are shown in [Table 11].

  As a result, in both Brazilian propolis extract and Chinese propolis extract, if the content of L-arginine is 30% by weight or more, a highly fluid powdery propolis extract can be obtained even after the stability test. It was. Although 30% by weight powdery Brazilian propolis extract powder has a slight decrease in fluidity after the accelerated test, propolis extract with an L-arginine content of 40% by weight or more is extremely fluid and stable even at high temperatures. It became clear that there was.

(Stability test result of extract composition of propolis origin plant containing L-arginine)
After crushing 5 g of dried shoots of shoots of Aleklin (Baccharis dracunculifolia), one of the plants originating in Brazilian propolis or Populus (Populus lassiocarpa), one of the plants originating in Chinese propolis, 15 g of 80% by weight The mixture was mixed with an aqueous ethanol solution and stirred at room temperature for 3 days. The mixture was squeezed and the supernatant obtained by filter filtration (6 μm mesh) was designated as alectrin and poplar extract (first squeeze), respectively. Further, ethanol was added to the squeezed residue and extracted in the same manner (second squeezing). Finally, these extracts were mixed into test Aleklin and poplar extracts. This was concentrated under reduced pressure to obtain 22% by weight of a liquid propolis-derived plant extract. 0.5 g of L-arginine was directly added to 5.6 g of the extract, stirred at 25 ° C. for 12 hours, freeze-dried according to Example 1, selected and collected with a mesh 30 to obtain a powder of plant extract of propolis origin. Obtained. A stability test and an acceleration test were performed using these as samples, and the fluidity of the samples was evaluated according to Comparative Example 1. The results are shown in [Table 12]. It was revealed that arginine has a high effect on pulverization of plant extracts derived from propolis. On the other hand, when arginine was not added (control), good results were not obtained in the stability test and the acceleration test.

(Stability test result of propolis extract composition containing poly-L-arginine)
10 mg of poly-L-arginine hydrochloride (manufactured by Wako Pure Chemical Industries, Ltd.) was added to 50 mg of 50% by weight ethanol aqueous solution and dissolved. 116.5 mg of Brazilian propolis extract (the solid concentration of the propolis extract was 20 wt%) extracted with 99.5 wt% ethanol was added thereto, and the mixture was vibrated with a shaker for 12 hours. According to Example 3, the solid obtained by freeze-drying at −20 ° C. was ground in a mortar. A powdery propolis extract with a poly-L-arginine content of 30% by weight was thus obtained. With respect to this sample, the stability test, the acceleration test, and the evaluation of the sample were performed according to Comparative Example 1. As a result (see Table 13), the powder of propolis extract added with polyarginine maintained high fluidity even at high temperatures.

Claims (11)

A powdery composition of propolis extract or plant extract derived from propolis, characterized by containing L-carnosine . L-carnosine is contained in an amount of less than 50% by weight, and the powder composition of the propolis extract or the propolis-derived plant extract according to claim 1. The powdery composition of a propolis extract or a propolis-derived plant extract according to claim 2, comprising less than 30% by weight of L-carnosine . 4. The propolis extract or the propolis origin plant extract according to any one of claims 1 to 3 , wherein the propolis origin plant extract is at least one selected from an extract of alectrine, eucalyptus, poplar, and jujube. A powdery composition. The propolis extract or propolis-derived plant extract is ethanol extract, hydrous ethanol extract, supercritical carbon dioxide extract, supercritical ethanol extract, supercritical water extract of propolis or propolis origin plant, The powdery composition of the propolis extract or the plant extract of propolis origin according to any one of claims 1 to 4 . A pharmaceutical, food-drinking, cosmetic, or oral composition comprising the propolis extract or the propolis-derived plant extract composition according to any one of claims 1 to 5 . The capsule formulation, granule formulation, or tablet containing the powdery composition of the propolis extract or propolis origin plant extract in any one of Claims 1-6 . Method for producing a propolis extract or propolis origin plant extracts, L- carnosine, or by mixing and stirring the solution, followed by powdered composition characterized by drying. The method for producing a powdery composition according to claim 8 , wherein the plant extract of propolis is at least one selected from extracts of alectrine, eucalyptus, poplar and jujube. The propolis extract or propolis-derived plant extract is ethanol extract, hydrous ethanol extract, supercritical carbon dioxide extract, supercritical ethanol extract, supercritical water extract of propolis or propolis origin plant, The manufacturing method of the powdery composition of Claim 8 or 9 . Method for producing a powdery composition according to any of claims 8 to 10, characterized in that dried by freeze-drying or hot air drying.