JPS625890B2 - - Google Patents

Description

[Detailed Description of the Invention] [A] Purpose of the Invention [Field of Industrial Application] The present invention uses the bark of Yellow oak as a starting material. (including quasi-drugs specified in
The goal is to obtain useful extracts.

[Conventional technology]

Yellow oak is one of the medicinal plants and herbal medicines that have been used in Chinese medicine and folk medicine for a long time. Recent applications of herbal medicines are not limited to internal medicines, but are increasingly being applied to external preparations for the skin and cosmetics for the skin and hair.

The main component of Huangbai is berberine, which has antibacterial and antibacterial effects.
Known for its anti-inflammatory effect. Here, a survey of recent publications regarding applications for external use on the skin reveals the following (1) to (9). However, although (9) uses yellow lotus, the main ingredient contains berberine, and it is already known that yellow lotus is used in the publication of (1), so it cannot be compared with the same type. It was considered and shown.

"Known Publications" (1) Fragrance Journal (Magazine) Special Issue No.
1 45-46 1979 (2) Published Patent Publication 1979-23918 (3) 〃 1980-125019 (4) 〃 1982-40609 (5) 〃 1982-53404 (6) 〃 1982-140014 (7) ) 〃 1984-1406 (8) Published Patent Publication 1988-88411 (9) 〃 1982-185210 [Problems to be solved by the invention] The development history of the present invention will be explained as follows. We succeeded in extracting a water-soluble extract containing . In other words, in order to use Huang Bao for external use on the skin, conventionally, its powdered form and extract containing berberine are mixed into a cream,
Methods of compounding it into emulsions, ointments, bandages, etc. are known, but recently there has been a desire to commercialize transparent water-soluble types, such as lotions and liquid-type formulations, by compounding them into external skin preparations. Unfortunately, in water-based products, sludge and precipitates occur over time after blending, and the sludge and precipitates must be removed by filtration each time. .

Basically, the method for producing an aqueous extract containing berberine is to first degrease Aspergillus orientalis using benzole, n-hexane, or ether as an organic solvent, and then add it to ethanol, methanol, or ethanol or water-miscible extract. A method of extraction in a methanol mixture was used, but with this method, the resulting crude extract often produced dregs and precipitates, and the filtration was repeated several times.
It was necessary to remove the sludge and sediment. As a result, the amount of berberine contained in purified extracts has the drawback of decreasing with each filtration.Furthermore, if filter aids such as perlite or diatomaceous earth are used for purification, berberine will be contained in sludge and sediment. At present, berberine is adsorbed by the filter aid, and in order to recover the berberine once adsorbed, a more complicated process is required.

In the case of aqueous liquid products for external use on the skin that do not use emulsifiers or dispersants, the content of water or ethanol is high in the formulation, and under these conditions, scum and precipitates are likely to occur. No, yellow oak extract was desired.

[Means for solving problems]

In view of the above-mentioned drawbacks, the present inventors adopted a conventional extraction method, that is, using benzol, ether, or n-hexane, to extract extracts from degreased yellow oak in a mixed solution of water or ethanol or methanol. We began our research by collecting a sludge-like substance along with a large amount of precipitate over time from the crude extract obtained by extraction, and investigating what kind of component this substance was.

As a result, proteins, bitter oobacnon, limonene, phytin-like polysaccharides, sterols, and small amounts of linoleic acid and sitosterol were confirmed.
Furthermore, the occurrence of dregs and precipitates in these water-soluble extracts varies greatly depending on the organic solvent used for pretreatment during degreasing, as well as the temperature and operation time for degreasing. It was found that a large amount of protein was generated in the form of dregs and precipitates in the crude extract obtained by pre-defatting with benzol.

On the other hand, they discovered that when the water-soluble extract scum and precipitate obtained after these degreasing treatments are collected and applied to the skin, a smooth, glossy feeling can be obtained and it has a moisturizing effect.

Therefore, the present inventors have attempted to obtain a water-soluble extract with a high efficiency with less sludge or precipitates, and to remove components that were conventionally removed as sludge or precipitates and that have not been removed by pretreatment operations. In addition, we focused on degreasing substances, focused our research on the effective application of these degreasing substances, and completed an extraction method that eliminates waste.

That is, as shown in the following examples, the extraction method of the present invention uses a fatty acid ester in the pretreatment to obtain a liquid to which a soluble extract is transferred. Next, by using the residue to obtain an aqueous extract, the final aqueous extract has very little generation of dregs and precipitates.
Moreover, the fatty acid ester obtained in the pretreatment can be used as it is as an external preparation for the skin, thereby achieving the object of the present invention.

Example 1 To 1 part of Oriental oak, from various known fatty acid esters, for example, octyldodecyl myristate, neopentyl glycol-2-ethylhexanate (Cosmol 525 manufactured by Nisshin Oil Co., Ltd.), octyldodecyl oleate, isopropyl myristate, Any compound used in the formulation of cosmetics or external medicines, such as hexyl laurate, may be used, but it is preferable to select one compound with a boiling point of 80 to 100°C or higher, add 2 parts of it, 80-100
When digested at ℃ for about 2 hours with stirring,
This causes soluble components to migrate into the fatty acid ester used. Next, leave it to stand naturally and when it reaches room temperature, separate the fatty acid ester layer. still,
The residue obtained at this time is used for the aqueous extract in Example 2 or for the isolation of berberine in Example 3.

A centrifuge was used for fractionation in the above steps. Next, the aliquoted liquid was stored at -20°C.
After allowing it to stand overnight under freezing at ±5°C, it is returned to room temperature and then filtered to obtain the liquid. This liquid is hereinafter referred to as liquid A for convenience. This liquid A can be used as it is as a skin preparation for external use, or by being incorporated into the formulation of a skin preparation for external use.

Liquid A contains linoleic acid and sitosterol.
2.0-4.8%, other sterols 0.1-1.0%,
0.1-1.3% of bitter substances and bitter-tasting glycosides such as Oobacnon and limonene, and phytin-like polysaccharides,
Although protein was confirmed, berberine was found at zero or in very small amounts. In Example 1,
When obtaining Liquid A, a fatty acid ester was used, but instead of this, squalane, squalene, pristane, and other hydrocarbon fats and oils such as Pearleam No. 6 (manufactured by NOF Corporation) may be used. however,
When hydrocarbon oils and fats are used, if berberine or water-soluble extracts are subsequently obtained from the residue, dregs and precipitates will not be generated by only smooth operations as shown in Examples 2 and 3 below. As a result, a decrease in absorption capacity is observed.

Example 2 The residue obtained by centrifugation in the process of Example 1 contains about 1-5% fatty acid ester. To remove this, n-hexane,
The fatty acid ester in the residue is transferred using one of the ethers. This allows the fatty acid ester in the residue to be easily removed.
For 1 part of the residue after the above organic solvent treatment, 1 part of a polyol solvent such as butylene glycol or propylene glycol and water was added to 20 parts of a 1:1 mixture solution while stirring at 80 to 100°C. Digestion for hours or add a 1:1 mixture of ethanol and water to 1 part of the residue after the above-mentioned organic solvent treatment.
Digestion is carried out in 20 parts at 60-80° C. for 1 hour with stirring. After digestion, the mixture is left to stand until it reaches room temperature, and then the extract is separated using a centrifuge. The fractionated extract is allowed to stand overnight in a freezer at -20°C plus -5°C, then returned to room temperature and filtered to obtain a filtrate. This filtrate is hereinafter referred to as liquid B for convenience.

Liquid B can be used as it is as an external skin preparation, but it can also be used by adding an appropriate amount into the formulation of an external skin preparation.

When the B solution is concentrated to dryness under reduced pressure using an evaporator, 140 to 240 g of water-soluble extract is obtained per 1 kg of residue. It also contains 38-40g of berberine. Even when this dry solid product is diluted with water again, almost no sludge or precipitate is observed.

Example 3 The residue obtained in the step of Example 1 was preliminarily adsorbed into the residue using an organic solvent such as n-hexane or ether, as shown in Example 2. After removing the fatty acid ester, water was added at a ratio of 20 parts to 1 part of the residue after the organic solvent treatment, and the following operations were carried out at 80 to 100 °C according to Example 2. Digestion is carried out for 1 hour under heating. After completing the digestion, separate the aqueous layer and leave it in a freezer at -20°C ± 5°C overnight. Next, after returning the temperature to room temperature again, the supernatant liquid is collected and concentrated to dryness using an evaporator.
240g is obtained. This dry matter contains 30 to 40g
Contains berberine. This dried product is hereinafter referred to as C extract for convenience.

Even when C extract is redissolved in water, almost no deposits or precipitates are observed, and it can be used not only for external preparations for the skin but also for internal preparations.
In addition, when blending into cosmetics etc., C extract,
It may be mixed with a liquid dissolved in advance at an appropriate concentration. Furthermore, it can be used for isolating berberine.

Example 4 One part of fine pieces or powder of Aspergillus orientalis is soaked with 3 to 5 parts of one of ether, n-hexane, or benzene while stirring. The components are mainly transferred to the organic solvent layer. At the same time, a portion of proteins, bitter substances, etc. are also transferred to the organic solvent layer. Therefore, after separating this organic solvent layer portion, the organic solvent is distilled off and concentrated using an evaporator to obtain a wax-like or paste-like material.
Hereinafter, this concentrate will be referred to as D oil and fat for convenience.

If D oil is used as it is as a skin preparation for external use, scum and deposits will be formed in the oil base used for the skin preparation. In particular, it increases in liquid oil. To prevent this, we used the same method used in Example 1, in which fatty acid ester was heated at 80 to 100°C, D fat was added, dissolved, and then filtered. It's not enough. In this method, for example, when added to olive oil, etc., sludge and precipitates are generated over time. Therefore, after separating the above-mentioned organic solvent layer, it was left to stand for a day and night in a freezer at -20°C ± 5°C, then returned to room temperature, and then filtered. I tried switching to a method of obtaining a wax-like or paste-like product by concentrating the liquid while distilling off the organic solvent using an evaporator. This concentrate is hereinafter referred to as D-1 fat for convenience.

D-1 oils and fats are used for external skin preparations (including cosmetics)
used for. Completely dissolved in all oil bases,
The occurrence of sludge and sediment is hardly observed.

However, in Example 4, it was shown that n-hexane, ether, and benzole were used as organic solvents.
- It is observed that more sludge and precipitates tend to migrate than when hexane or ether is used, so it is more advantageous to use n-hexane or ether from an operational point of view.

Example 5 The D-1 oil obtained in Example 4 above has a content of linoleic acid and sitosterol.
Contains 20-30% and other fatty acids derived from Aspergillus orientalis, and is used in external skin preparations (including cosmetics).
Considering the wide range of prescription applications, D-1 oil and fat further dissolved in the precipitated ester employed in Example 1 also has higher stability. The dissolution conditions at that time include linoleic acid,
As a guideline, the sitosterol content should be adjusted to 2.0 to 4.8%.
This adjustment liquid is hereinafter referred to as D-1 liquid for convenience. D-
Part 1 provides a slippery feeling effect similar to that of Part A, and is particularly easy to add to liquid fats and oils.

In Examples 4 to 5, D oil and fat, D-1 oil and fat,
The basic operation of liquid D-1 is to carry out a treatment known as a degreasing process as a pretreatment operation from so-called yellow oak or yellow lotus when obtaining conventionally known berberine or a water-soluble extract containing berberine. This is based on the effective use of the degreasing substance components.

[C] Effect of the invention Liquid A obtained in Example 1 of the present invention or
An example of applying the D-1 oil obtained in Example 4 and the D-1 liquid prepared in Example 5 to a skin external preparation is as follows.
I can't find anything else. On the other hand, B obtained in Example 2
There are no other reports on the production of a water-soluble extract from Oriental oak using the liquid or the C extract obtained in Example-3, nor any examples of its use in external preparations for the skin.

In other words, extracts such as liquid B and extract C that are dissolved in water and do not form any deposits or precipitates over a long period of time can be used as external skin preparations in the form of liquid products, such as lotions, etc. Easy to incorporate into water-based products. In particular, with conventional water-soluble extracts, when the liquid product contains a high amount of ethanol, scum and precipitation occur over time, and because of this, filtration and other steps are required several times in the final process of the product. Previously, methods were used to remove the cage and sediment, but this is unnecessary. Of course, the final products shown in Examples 1 to 5 are all creams, emulsions, lotion-type skin products, hair care products,
It can be used by incorporating it into ointments, adhesive plasters, wiping papers, and cloths.

As can be understood from the extraction process, the extract of Aspergillus orientalis obtained by the method of Examples 1 to 3 is not wasted. It is a great achievement that we were able to recover the fat-soluble components that had been present and effectively utilize them based on the results of Example 1.

There is no need to explain the medicinal effects of liquid B and extract C obtained in Examples 2 to 3, which are extracts containing berberine.
It exhibits anti-inflammatory, antibacterial, and water-retaining effects, but
Particularly in the case of liquid B, the water retention effect is enhanced. This is thought to be due to the fact that in addition to berberine, Liquid B contains flavonoid components and phenol compounds.

On the other hand, C extract can be used in the formulation of internal medicines and skin external medicines, but it can be used in advance with water, a mixture of water and ethanol in a ratio of 1:1, or
When converting to berberine content as the content of C extract in a mixture of water and polyol solvent, propylene glycol and butylene glycol at a ratio of 1:1, a solution adjusted to 0.14 to 0.24% is an aqueous type. As a transparent liquid product, it is easier to blend.

Next, the liquid A obtained in Example 1, which does not contain berberine, mainly contains fat-soluble components such as linoleic acid and sitosterol in the fatty acid ester used in the step, and also contains bitter substances. However, the effects of this liquid A include good lubricious feeling on the skin,
It has the following effects.

After cutting off the hair on the back of the mouse, small incisions were made on both sides of the back using a scalpel on the epidermis treated with a depilatory agent, and Solution A was applied once a day to one side, while the other side was left unapplied. When observing the process leading to healing, it was found that the treated areas healed quickly, and at the same time, the length of cut hair also accelerated.

On the other hand, in the non-applied area, edema was observed around the cut area made by the scalpel, but in the applied area, there was little edema. This effect is due to the 20% of liquid A and B.
Observations can be made with the diluted solution, the solution prepared by diluting the adjusted diluted solution of C extract 20 times, D-1 oil, and D-1, but rather, the number of days for healing is different from that of solution A or D-1. showed a tendency to be faster. Furthermore, the hair elongation rate was remarkable for solutions A and D-1.
Therefore, it can also be incorporated into hair growth agents. Substances that exhibit such a hair elongation (growth) promoting effect are thought to include bitter components such as octopus, linoleic acid, and sitosterol, but these are still unknown.

Example of combination prescription 1 The prescription prescribed by the Japanese pharmacies includes petrolatum, hydrophilic ointment,
In the water-absorbing ointment, add 0.3 to 10 of liquid A obtained in Example 1.
% or D-1 fat obtained in Example 4 0.3~
10% or D-1 liquid obtained in Example 5 0.3-10
% under heating to prepare ointments.

Formulation example 2 In accordance with known cream and emulsion formulations, add 0.1 to 10% of Part A or D-1 oil or fat or D-1 together with other fat bases under heating to prepare cream or emulsion. Manufacture.

Combination Prescription Example 3 In the formulation of a topical lubricant using known creams, emulsions, other emulsifiers, dispersants, and suspending agents, together with Liquid A or D-1 oil or fat, or Liquid D-1,
A suitable amount of liquid B or extract C is added to prepare a skin preparation for external use. However, when using liquid B or extract C, the content of berberine in the product manufactured is as follows:
A good guideline is about 0.001% to 0.23%.

Formulation example 4 Add an appropriate amount of liquid B or extract C to the formulation of a lotion or a known aqueous external preparation containing ethanol to prepare a liquid product. At this time, for cosmetics, the amount of berberine in the product is 0.001~
One guideline for the content is about 0.01%, and for external medicines (including quasi-drugs), the content is about 0.001 to 0.23%.

Claims (1)

[Claims] 1. The boiling point of the fatty acid ester is
Add 2 parts of 1 type to 80 to 100℃ or higher.
After digestion under heating at ~100°C, the fatty acid ester layer portion (A layer portion) and the residue portion (B layer portion) are separated.
The layered portion is allowed to stand still under freezing at -20°C±5°C, and then filtered to obtain a liquid containing fatty acid ester soluble components in yellow oak (liquid A). On the other hand, the B layer part is n-
After removing the fatty acid ester still remaining in the B layer using hexane or ether, a mixture of water and propylene glycol, water and butylene glycol in a 1:1 mixing ratio, or water and ethanol is added. Using a 1:1 mixture, add 20 parts to 1 part of layer B, digest at 60 to 100°C, separate this liquid layer, and heat at -20°C. ±5℃
1. A method for producing a liquid containing a yellow oak extract, which is characterized in that a water-soluble extract-containing liquid (liquid B) is obtained by leaving the liquid in a freezer and then filtering it. 2 Liquid A obtained from Huangbai contains 2.0 to 4.8% of linoleic acid and sitosterol, while liquid B contains 0.14 to 4.8% of berberine.
1. The method for producing a liquid containing Aspergillus orientalis extract according to claim 1, characterized in that the liquid contains 0.24%.