JPS5820583B2 - solid royal jelly - Google Patents

Description

[Detailed description of the invention] The present invention relates to a novel solid royal jelly.

The substance of the present invention is solid royal jelly composed of royal jelly and cyclodextrin, and its main advantage is that it can maintain its blood flow increasing activity for a long period of time without reducing the blood flow increasing activity of royal jelly. .

Royal jelly has been widely used as a nutritional health food, and its usage is increasing year by year.

Although there are still some unknowns about the ingredients of royal jelly, it is known that it is highly nutritious for the human body and has desirable physiological activities.

Royal jelly's physiological activity is known to be colored, but there are few quantitative numerical values.

Therefore, it is unclear whether royal jelly maintains its activity stably and effectively when ingested, and therefore it is difficult to widely utilize Royale IJ-. As a result of many years of research to overcome these difficulties, it was discovered that the physiological activity of royal jelly has an effect of increasing blood flow, and it was also found that this blood flow increasing effect could be captured numerically.

By being able to capture this effect numerically, it is possible to numerically determine the stability of royal jelly.

The blood flow increasing effect was measured using experimental animals weighing 8 to 10 mm.
Using a dog (female) weighing 1 kg, changes in hindlimb vascular blood flow are measured.

The animal is anesthetized, and a blood vessel probe connected to a blood flow meter is attached to its femoral artery.

A sample is administered, changes in blood flow that occur in the artery are captured as voltage, the signal is calibrated using an electromagnetic blood flow meter, the signal is amplified using an amplifier, and the data is read using an oscilloscope.

[Masato Shinoyama et al., “Star Medicinal Dog Bulletin J 13, 109 (197
See 1)].

This effect was expressed at a dose of 5 μg of royal jelly,
An increase in blood flow of 5-60 ml/min is observed for doses of 5-1000 μI, with a linear relationship between dose and response.

We also measured the effects on blood flow of various flowers and vitamins as substances related to royal jelly, and compared the activity per unit weight when the activity of royal jelly was set as 100. As shown in the table.

As is clear from Table 1, all types of honey have a slight effect on increasing blood flow, but their activity is about 1/100 to 1/200 that of royal jelly, while the vitamins used In all cases, the dosage is 50~
No change in blood flow was observed within the 250 μg range.

This blood flow increasing factor is relatively stable when treated with acid, but when treated at pH 8.0, it decreases to about 30 after 4 hours, and when treated with alkaline, it is rapidly inactivated.

It also has a constrictive effect on the isolated intestinal tract of the guinea pig,
Its action is royal jelly 0.5-15 μg ArLl (
(final concentration) and increases with increasing concentration.

In order to clarify the blood flow increasing factors in royal jelly, gel filtration was performed on the water-soluble fraction of royal jelly.

Add 154mM Nacn (physiological saline) 5mA to Royal Jelly 534~, stir and extract under water cooling for 1 hour,
When gel filtration was performed on the supernatant after centrifugation at ooo; rpm for 20 minutes, it was separated into several fractions based on absorbance in ultraviolet light and reactions of proteins, sugars, etc.

The dog blood flow increasing activity and the guinea pig isolated intestinal tract contracting activity were both eluted as a single peak J around V,/Vo1.6.

Royal jelly, as is well known, is a liquid substance extracted from the crown of the honeycomb.

Commercially available royal jelly has a water content of 62.5~
It is roughly divided into three types: raw royal jelly with a water content of 68.5%, dried royal jelly with a water content of J5.0 or less, and adjusted royal jelly.

Fresh royal jelly is the raw material that is put in a container and packaged.Dried royal jelly is the raw royal jelly that has had more than 90% of its water removed by a method such as vacuum freeze-drying. Royal jelly is raw or dried and processed into tablets, capsules, and other dosage forms using lactose, starch, fats and oils, other conditioning agents, or food additives.

Compared to other forms of royal jelly, raw royal jelly requires almost no processing after the raw milk is collected, so it can be said to be ideal because it can fully utilize the potency of royal jelly.

However, it is preferable for raw milk to be collected within a short period of 48 hours after migration, from the viewpoint of quality assurance and economical collection, and raw milk must be kept at a constant temperature (5 to 8°C). Products filled in small bottles must also be kept refrigerated, and if they are not kept cold with dry ice or the like during packaging and transportation, their effectiveness will rapidly decline.

As described above, hygiene management and refrigerated storage are important and indispensable for fresh royal jelly, which has the disadvantage of being troublesome to handle and costing too much at the distribution stage.

Dried royal jelly is obtained by removing water from raw royal jelly by a method such as freeze-drying, as described above, and was devised to prevent the effectiveness of raw royal jelly from decreasing.

However, even with this method, it is difficult to completely maintain the potency of raw royal jelly for a certain period of time, and freeze-drying is disadvantageous in that it is expensive.

Dried royal jelly is mainly used for producing adjusted royal jelly.

As mentioned above, prepared royal jelly is processed into dosage forms such as tablets and capsules, and has the advantage of being easier to store than fresh royal jelly. However, it has the disadvantage that the activity of fresh royal jelly tends to decrease due to solvent treatment or the like.

Therefore, conventional products such as fresh royal jelly, dried royal jelly, and adjusted royal jelly all have advantages and disadvantages in their characteristics, and it is difficult to say that they are the gold standard.

Therefore, obtaining royal jelly products that are free from the various drawbacks mentioned above is very meaningful, if not necessary, in view of the great impact it has on people's health. No.

Among them, the shipping value and final retail price of adjusted royal jelly is approximately twice that of fresh royal jelly, and it is important to obtain excellent adjusted royal jelly.

The present inventor has arrived at the present invention as a result of research into ways to avoid such disadvantages and to stably maintain the blood flow increasing activity of royal jelly.

That is, the present invention relates to solid royal jelly comprising royal jelly and cyclodextrin.

The solid royal jelly of the present invention is a novel substance that has not been previously known.

The solid royal jelly of the present invention does not require the labor and expense of freeze-drying, and is a solid substance that does not impair the blood flow increasing activity of the royal jelly itself, compared to conventional prepared royal jelly.

The blood flow increasing activity of royal jelly can be maintained for a long period of time.

Even when the solid royal jelly of the present invention is made into a dosage form such as granules or tablets, the blood flow increasing activity of the royal jelly is stably maintained.

For example, the royal jelly of the present invention has 100%
It has an excellent effect in that its blood flow increasing activity does not decrease even after days have passed.

This excellent effect was completely unexpected.

The cyclodextrin used in the present invention is
It is a cyclic dextrin obtained by the action of special microorganisms or enzymes on starch or dextrin, and its characteristic feature is that it has a donut-shaped molecular structure and has cavities of about 6 to 10 people in diameter inside. .

There are three types of cyclodextrin, α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin, depending on the number of constituent units of d-glucose. May be used.

β-Cyclodextrin is a white crystalline powder with the molecular formula (Ca Hlo 05 ).
? It is shown as 1135. Melting point 300-305°C
(decomposition).

In addition, the acute toxicity of β-cyclodextrin is >12.5 g/kg orally in mice and >12 g/kg in rats.
．． It is OgA&.

Regarding chronic toxicity in rats, no changes were observed in blood, clinical biochemical, and histopathological findings even after daily oral administration of 1.697 kg for 6 months.

Therefore, cyclodextrin is a naturally occurring edible substance, and based on these acute and chronic toxicity tests, β-cyclodextrin is considered to be an extremely safe substance. Cyclodextrin is a donut made of glucose. It is known that, as a characteristic of the molecular structure, it forms inclusion compounds with various substances such as hydrocarbons, steroids, and terpenes of small to medium molecular weight.

Therefore, cyclodextrin can be called a microcapsule at the molecular level.

However, inclusion of highly polar substances such as amino acids is considered difficult.

The present inventor conducted various experiments in order to encapsulate royal jelly with this molecular microcapsule, and was able to achieve this.

Although there are various methods for producing the solid royal jelly of the present invention, the kneading method is preferred.

In carrying out the kneading method, for example, water (about 0.1 to 1 times the weight of cyclodextrin) is added to cyclodextrin to form a paste.

Royal jelly in an amount of about 0.5 to 2 times the weight of cyclodextrin is added to this and kneaded.

The kneading time is approximately 4 to 10 hours.

After kneading, if you want a final product in the form of granules, knead as is or with an appropriate amount of excipients such as lactose, starch, or cyclomethylcellulose added.

The obtained granules are then aerated or dried under reduced pressure to obtain the desired product.

According to the present invention, solid royal jelly can be obtained by such a simple method.

The content of royal jelly in the solid royal jelly of the present invention can generally be about 30 to 60 parts.

In the solid royal jelly of the present invention, royal jelly is considered to be included in cyclodextrin, and this means that, for example, solid royal jelly loses the characteristic odor of royal jelly, but when it is poured into hot water, This can be seen from the fact that by doing so, the unique smell is reproduced.

This clearly indicates that royal jelly is microencapsulated at the molecular level.

Next, the blood flow increasing effect of the solid royal jelly of the present invention will be shown.

That is, 150 g of β-cyclodextrin and 50 g of purified water.
After adding m1 and stirring for a short time, Royaleze IJ-15
Add 0g and mix thoroughly.

After kneading, 300 g of lactose is added to the mixture, and the mixture is further kneaded and passed through a sieve to form granules.

The resulting granules are dried at 20-23°C for 24 hours.

The dried granules are left at room temperature for 100 days.

Next, after pulverizing the granules, the royal jelly content is 50%.
The powder was accurately weighed so as to be ~, and extracted with about 75 TLl of physiological saline under water cooling with stirring for 1 hour.The total volume was made to 1001 rLl.The powder was centrifuged at 300 Orpm for 15 minutes, and the supernatant liquid was used for assay. .

This is designated as sample B. On the other hand, Royalze IJ-150g
and 300 g of lactose, knead thoroughly, and pass through a sieve to form granules.

The resulting granules are dried at 20-23°C for 24 hours and then left at room temperature for 100 days.

Next, it was treated in the same manner as Sample B to obtain a supernatant, which was used for assay.

This is designated as sample A.

The assay was based on the method for measuring vascular blood flow in the hind limbs of dogs described above.

The results obtained are shown in Table 2.

As is clear from the results in Table 2, the effects of the solid royal jelly of the present invention are extremely significant compared to conventional solid royal jelly.

The solid royal jelly of the present invention may be administered as it is in the form of granules, or the granules may be formulated into tablets, or the granules may be packed into capsules and administered.

In its formulation, additives commonly used in formulation can be used.

As described above, the solid royal jelly of the present invention can maintain the blood flow increasing activity of royal jelly for a long period of time.

Furthermore, in the present invention, the royal jelly is not in the usual sill shape.

Since it is in solid form, it is convenient to transport and is extremely convenient to take.

Furthermore, when this solid royal jelly is orally administered, it is easily released within the digestive tract, so that the physiological activity of the entire amount of royal jelly contained in the solid royal jelly can be advantageously utilized.

Next, examples will be shown.

Example 1 150 y of β-cyclodextrin was placed in a tabletop kneader, 50 d of purified water was added thereto, and the mixture was stirred for 3 minutes, followed by adding 150 g of Royale IJ-1 and kneaded for 7 hours.

After kneading, the mixture is sieved through an llnm sieve to form granules.

The obtained granules are dried at 20 to 23°C for 24 hours and then sized.

The obtained granules have lost the odor characteristic of royal jelly and contain 60 parts by weight of royal jelly.

Example 2 150 g of β-cyclodextrin was placed in a tabletop kneader, 50 g of purified water was added thereto, and the mixture was stirred for 5 minutes. Then, 1 liter of Royaleze IJ-15 was added and kneaded for 8 hours.

After kneading, add 300g of lactose to this and add 1 more
Knead for 5 minutes and sieve through a 1 mm sieve to form granules.

The obtained granules are dried at 20 to 23°C for 24 hours and then sized.

The obtained granules have lost the odor characteristic of royal jelly, and have a royal jelly content of 30 parts by weight.

When these granules are poured into hot water, the characteristic odor of royal jelly is recreated.

Comparative example The granules prepared by the method of Example 1 are referred to as sample A.

On the other hand, Sample B is a commercially available granule produced by freeze-drying.

Samples A and B each have a royal jelly content of 507Q.
/200 ■ and leave it at room temperature for 100 days.

After leaving it for a while, the blood flow increasing effect is measured by measuring blood flow in the dog's hind limbs.

When the blood flow increasing activity of sample A was set as 100, that of sample B was 52.1.

Claims (1)

[Claims] 1 Solid royal jelly consisting of royal jelly and cyclodextrin.