JPS6150922A - External drug for skin containing extracted component of "oubaku" - Google Patents

Abstract

PURPOSE:To obtain an external drug for skin, giving smooth feeling to the skin and having hair-growing effect, by extracting OUBAKU (bark of Phellodendron amurense) with a fatty acid ester, leaving the ester layer at rest under freezing, filtering the layer, and using the obtained OUBAKU component soluble in fatty acid ester as an active component. CONSTITUTION:1pt. of OUBAKU is added with 2pts. of a fatty acid ester having a boiling poing of >=80-100 deg.C, immersed at 80-100 deg.C, and separated into the fatty acid ester layer and residue. The ester layer is left at rest at about -20 deg.C, and filtered to obtain a component soluble in a fatty acid ester and useful as an external drug for skin. The residue is defatted with n-hexane, etc., immersed in 20pts. of a 1:1 mixture of water and propylene glycol, based on 1pt. of the separated residue, at 80-100 deg.C, left at rest at -20 deg.C, filtered, and concentrated to obtain a water-soluble extract useful as an external drug for skin. The fat-soluble component of OUBAKU which has been discarded so far can be used as an external drug for skin.

Description

[Detailed Description of the Invention] [A] Purpose of the Invention [Field of Industrial Application] The present invention is directed to the use of yellow cypress bark, which is extracted (eluted) using a fatty acid ester, from the bark of the yellow cypress tree as a raw material. Use of the ingredients in pharmaceuticals, cosmetics, or external skin preparations. Furthermore, after elution using fatty acid ester,
To obtain an aqueous extract containing a high content of berberine and with very little occurrence of sludge by using the residue of Aspergillus as a raw material, and to use this as an external preparation for the skin, and on the other hand, a known method for extracting berberine from Aspergillus orthus Alternatively, when obtaining a water-soluble extract, a degreasing operation is employed using a growth solvent such as n-hexane, ether, penzole, etc., and this is removed.
! However, it has been collected and dissolved in fatty acid ester, and this is also used in external preparations for the skin. By the term "external skin preparations" here, we mean cosmetics, pharmaceuticals, and quasi-drugs for the skin or hair that are used in forms other than oral administration or injections, as defined by the country's Pharmaceutical Affairs Law. As expected.

[Conventional technology]

351" Kasu is one of the representative herbal medicines known as Chinese medicine or folk medicine. It is also listed in Japan (JP). It is known as the main ingredient for external use (external preparation). There is an antibacterial effect of berberine, and 'f' has been used since ancient times.
X.Bunches - There are applications using powders, water-based extracts (base extracts, etc.), tinctures, etc. For this reason, attempts have naturally been made to use powdered yellow oak or water-based extracts in cosmetics.

Recent publications that apply the anti-inflammatory and antibacterial effects of yellow oak to external skin preparations include (1) listed below, as well as (2) to (9). There are several published patent publications.

(1) 7 Régrance Journal (Magazine) Extra Issue No.
, 1.45-46 1979 (2) Published Patent Publication 1979-23918 (3) l
l Showa 5O-125019 (4) 〃
Showa 56-40609 (5)
1986-53404 (6) 〃 1980-185210 (7) 〃 1982-14
0014 (8)〃 1984-14-06 (9
) It l 59-88411 Among the above publications, (6) uses yellow lotus, but in (1), it is already mentioned that yellow lotus and yellow lotus have been used for skin or cosmetics. Since the main component is berberine, it is classified as a similar substance.

[Problem that the invention seeks to solve]

To explain the history of the development of the present invention, the original research theme was how to obtain berberine contained in the quality phase or an aqueous extract containing berberine more efficiently and in a higher yield. , ζ The methods that have been adopted include removing the lipids from the extract to obtain a crude extract, and then purifying it, or directly extracting it using a water-soluble growth solvent (ethanol, methanol, etc.).

According to these conventional methods, the drawback is that a large amount of sludge or precipitate is generated in the extract, and in order to remove this, filtration and other methods are used many times. Filtration is required, so that the berberine content in the final product is low. Particularly when an aqueous extract contains a high amount of berberine, if it is dissolved in water, the occurrence of dregs increases over time. For that purpose, we need salves, bandages, creams, etc. Even if it can be incorporated into L-liquid, lotion, etc. type dosage forms or powder-type dosage forms, other ingredients used in the formulation may not be included in water-based transparent liquid products. Due to this, the occurrence of sludge and sediment has increased, and as a means to prevent this, filter aids such as perlite and clay have been used.

In addition, examples of extracts mainly consisting of fat-soluble components contained in the substance being used for the skin of cosmetics, etc. are as follows:
I haven't seen it anywhere else until now.

The original purpose of the present inventors was to improve the conventional method. As a first step to that end, first, using the conventional method,
A water-soluble crude extract with a high content of berberine is made, and then the scum and precipitate that occur over time are collected.
We analyzed the main components of this causative substance.

As a result, even for desk extracts that have been previously degreased using ether, penzol, n-hexane, etc., ethanol or methanol alone or in a mixture with water can be used without pretreatment. In the crude extract obtained from this process, common oliy-like substances or precipitates were found, including the bitter substances Oobacnone and limonene, as well as proteins, linoleic acid, sitosterol, sterols, and high-molecular phytin-like polysaccharides. It came to be.

In the degreasing operation, the above-mentioned solvent is used, and if this operation is performed in the absence of light, the lipids will naturally form in the form of an olivine. On the other hand, in the degreasing process during pre-treatment, even when completely treated and removed using the above-mentioned solvents, sludge-like substances are generated, and most of them are protein-based. It was found that the oli-like matter and precipitate of the crude extract extracted using a water-soluble solvent such as methanol are rich in both lipids and proteins. Therefore, with less sludge and sediment,
I decided to continue my research on how to obtain an aqueous extract.

[Explanation] Structure of the invention [Means and effects for solving the problems] The present inventors discovered the following when analyzing the oli-like substances and precipitates recovered from the crude extract obtained by the above-mentioned conventional method. When this substance adhered to the skin and tried to wipe it off, it was discovered that a very pleasant and slippery feeling was obtained.

Therefore, the present inventors conducted research on extracting an aqueous extract or berberine at a high efficiency, and on the other hand, simultaneously collected oli-like substances or precipitates that were conventionally removed or discarded. We focused our research on applying this to topical skin preparations.

As a result, each of the extracts obtained by the extraction methods shown in the Examples below can be used as a skin preparation, and the object of the present invention was achieved.

"Example 1" For example, octyldodecyl myristate, Neobenchi!, etc. are added to 1 part of Aspergillus from various known fatty acid esters. Reglycol-2-ethylhexanate (Cosmol 525
Nisshin Oil Co., Ltd.), octyl thicil oleate, impyl myristate, hexyl laurate, etc., which are used in the formulation of cosmetics and external pharmaceutical preparations, may be used, but preferably have a boiling point of 80 to 100. Select one type of thing from ℃ to
When digestion is carried out at 0 to 100°C for about 2 hours with stirring, soluble components migrate into the fatty acid ester used. Separate the ester layer. The residue obtained at this time is used for the aqueous extract in Example 2 or for the isolation of berberine in Example 3.

The fractionation in the above-mentioned steps was carried out using a centrifuge. Next, the fractionated liquid was stored at minus 20°C ± 5°C in an apparatus for day and night, then allowed to stand at room temperature, and then filtered.
Get that liquid. For convenience, this liquid will be referred to as Liquid A hereinafter.This AFOL 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.

In liquid A, 9-nolic acid and cytokyutyrol are present at a concentration of 2°0~.
1.8%, 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 is confirmed, berberine is zero or very low.
6 In Example 1, fatty acid ester was used when obtaining liquid A, but instead of this, squalane, squalene, pristane, and others, Pearleam N: 0.6 (manufactured by NOF) were used. Hydrocarbon oils and fats may also 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 cannot be produced by only smooth operations as shown in Examples 2 and 3 below. This results in a decrease in yield.

"Example 2" The residue obtained by centrifugation in the process of Example 1 contains about 1-5% of 73rI costate ester.

In order to remove this, one type of n-hexane or ether is used to transfer the fatty acid ester in the residue. As a result, the amount of fatty acids in the remaining figurines is
easily removed.

For 1 part of the residue after the above-mentioned if-containing solvent treatment, 80 to 1
Digestion for 1 hour with stirring at 00"C, or
For 1 part of the residue after the above-mentioned organic solvent treatment, ether/
- 60 to 80° in 2OiB of a 1:1 mixture of water and water.
c-Ch Digestion is performed for 1 hour while stirring. After incubation, the mixture is left to stand until it reaches room temperature. Next, the extract is fractionated using a centrifugal am. The fractionated extract is kept in a freezer at -20°C plus -5°C day and night, then returned to room temperature and filtered to obtain a filtrate. This filtrate is hereinafter referred to as liquid B for convenience.

B8L 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, a residue IKg1. : On the other hand, 140 to 240 g of water-soluble extract is obtained. Also, as berberine, 38
Contains ~40g. Even when this dry solid product is diluted with water again, no sludge or precipitate is observed.

"Example 3" The residue obtained in the process of Example 1 was preliminarily adsorbed into the residue using an organic solvent such as n-hexane or ether in the same manner 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. under heating of
'Perform 11 hours of digestion; after completing the digestion, the water M
Take aliquots and store them in a freezer at -20℃±5℃.
Next, after returning the temperature to room temperature again, the liquid was collected and concentrated to dryness using an evaporator, resulting in a residue of Ikg! , : On the other hand, the yield is 140
~240 g are obtained. This dry matter contains 30 to 40
Contains g of berberine. This dried product is hereinafter referred to as C extract for convenience.

Even when C extract is redissolved in water, no scum or precipitate is observed, and it can be used for external preparations for the skin as well as internal preparations.

Furthermore, when blending into cosmetics, etc., C extract may be mixed in advance with a liquid dissolved at an appropriate concentration.

Furthermore, it can be used for isolating berberine.

[Example 4] Ether, n-
When 3 to 5 parts of hexane or penzole are used and cooled while stirring, the fat-soluble components in the poor phase are mainly transferred to the solvent layer.

At the same time, a portion of proteins and bitter substances are 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 fats and oils for convenience.

D oils and fats can be used as is as a skin preparation for external use.
Formation of scum and precipitates is observed in the oil base used for external skin preparations. In particular, it increases in liquid oil. As a method to prevent this, using the artificial chilled fatty acid employed in Example 1, 80 to 100
A method was used in which oil and fat D was added and dissolved under heating at 0.degree. C., and then filtered, but this method is still insufficient. In this method, for example, when added to olive oil, etc., sludge and precipitates are generated over time. Therefore, after separating the organic solvent WfIg mentioned above, it was placed in a freezer at -20°C ± 5°C for -M overnight, and then returned to room temperature, and then filtered, and the resulting filtrate was Originally, I tried switching to a method of distilling off the organic solvent using an evaporator and concentrating it to obtain a wax-like or paste-like product. This concentrate is hereinafter referred to as D-1 oil pan for convenience.

D-1 oil and fat are completely dissolved in all oil and fat bases used in external skin preparations (including cosmetics), and the generation of scum and sediment is hardly observed.

However, in Example 4, n-hexane,
The use of ether and penzole was shown, but when using penzol, more sludge and precipitates tend to be transferred than when using n-hexane or ether, so it is difficult to operate. It is more advantageous to use n-hexane or ether.

"Example 5" The D-1 fat and oil obtained in Example 4 described above had the following:
The content of sulfuric acid and sitosterol is 20-30%,
In addition, it contains fatty acids derived from Aspergillus orientalis, but considering its use in external skin preparations (including cosmetics) and wide MH prescriptions, D-1 oil was further adopted in Example 1. Those dissolved in fatty acid esters have even higher stability. In this case, the dissolution conditions should be adjusted so that the content of linoleic acid and sitosterol is 2.0 to 4.8% as a guideline. Liquids 0 and D-1, referred to as liquid 1, provide almost the same slippery feeling effect as liquid A, and are particularly easy to add to liquid oil JJitM.

In Examples 4 and 5, the basic originals of D-oil, D-1 oil, and D-1 liquid are from so-called Huangbai and Huanglian, which are used to obtain conventionally known berberine or water-soluble extracts containing berberine. As a pre-treatment technique, we aimed to effectively utilize the degreasing substance components based on what is known as a degreasing process.

[C] Effect of the invention Liquid A obtained in Example 1 or Example 4 of the present invention
No other examples have been found in which the D-1 oil and fat obtained in Example 5 and the D-1 liquid prepared in Example 5 were applied to external skin preparations. On the other hand, liquid B obtained in Example 2 and liquid C obtained in Example-3
Ike has not found any reports on the production of water-soluble extracts from Oriental oak, nor any examples of its use in external preparations for the skin.

In other words, extracts such as liquid B and extract C (extracts that dissolve in water and do not cause any buildup or precipitation over a long period of time) can be used as external preparations for the skin, and when they are made of wood products, such as lotions. Especially with conventional water-soluble extracts, which are easy to incorporate into water-based products such as ethanol, when the liquid product contains a high amount of ethanol, scum and precipitation occur over time, which causes the final product to During the process, methods such as filtration were used many times to remove slag and sediment, but this is unnecessary.

Of course, the final products shown in Examples 1 to 5 include creams, emulsions, low-skin type skin products, hair care products, cartilage, bandages, wiping papers and cloths. It can be used by containing it in the class.

The quality phase extract obtained by the method of Examples 1 to 3 is as follows:
From the extraction process, it is understood that there is no swallowtail,
In addition, in Examples 4 and 5, it was a great achievement that we were able to recover fat-soluble components that were conventionally discarded or removed and achieve effective use based on the results of Example 1. be.

Example 2 of kissing in and out of hII containing berberine~
Regarding the medicinal effects of liquid B and extract C obtained in step 3, there is no need to explain them here; they exhibit anti-inflammatory, antibacterial, and water-retaining effects, but especially in the case of Bi,
Increases water retention effect. Is this B? [Judging from the ingredients inside, in addition to berberine, it contains 7 Lab/Ide type components and 7 E7 type compounds9, which may be the reason.

On the other hand, C extract can be used in the formulation of internal melon preparations and skin external preparations. , when converted to berberine content as the content of C extract in a 1:1 mixture with butylene glycol, it is 0.14 to 0.24%.
When the liquid is adjusted to 100%, it becomes an aqueous type transparent liquid product, making it easier to blend.

Next, the solution A obtained in Example 1, which does not contain berberine, contains s/- in the fatty acid ester used in that step.
It mainly consists of fat-soluble components such as acid and sitosterol.
Although it may contain bitter substances, the effects of this liquid A include a good slippery feeling on the skin, as well as the following effects.

After cutting the hair on the back of the mouse, 1. Make small incisions on both sides of the back using a scalpel, apply liquid A once a day to one side, and apply liquid A to the other side 1. If you observe the progress of healing without application, you will find that in the treated areas, the healing time is faster, and at the same time, the growth of clipped hair is faster.

On the other hand, in the non-applied area, edema was observed around the area cut by the scalpel, but in the applied area, there was little edema.

Such effects can also be observed in the 20-fold dilution of AQ and B solutions, the 20-fold dilution of the adjusted dilution of C extract, D-1 oil and fat, and D-1 solution R. On the contrary, the cure time tended to be faster for solutions A and D-1. Furthermore, the hair elongation rate was 2.0 for liquids A and D-1. Therefore, there are 8 combinations for hair punishment, etc. Substances that exhibit such a hair elongation (growth)-promoting effect include bitter-tasting ingredients such as Physcomitrella occidentalis, sulfuric acid, sitosterol, etc., but these are still unknown.

(Combination Prescription Example 1) According to the prescription shown in the day-to-day treatment, 0.3 to 10% of Solution A obtained in Example 1 is added to Vaseline, parent tree ointment, and water-absorbing cartilage, or
0.3 to 10% r)-1 oil and fat obtained in Example 4, or D-1 liquid () obtained in Example 5.

(~10% is added under heating to make soft shells.

(Example 2 of formulation) In accordance with known cream and emulsion formulations, add liquid A or D-1 oil or D- with other oil bases under heating.
Add 0.1 to 10% of liquid 1 to make cream or milky lotion.

(Example 3 of Formulation) When formulating a topical lubricant using known creams, emulsions, emulsifiers, dispersants, and suspending agents, liquid A or D-
A skin external preparation is prepared by adding an appropriate amount of liquid B or extract C together with liquid D-1 or oil or fat D-1. However, when using liquid B or extract C, it is recommended that the content of berberine in the product to be manufactured is approximately 0.001% to 0.23% (formulation example 4). Alternatively, a liquid product is prepared by adding an appropriate amount of liquid B or extract C to the formulation of a known aqueous external preparation containing ethanol. At this time, the amount of berberine in the product is about 0.001 to 0.01% for cosmetics, and 0.001 to 0.01% for external medicines (including quasi-drugs 31S).
One guideline is a content of about 23%.

Claims (3)

[Claims] (1) The boiling point of the fatty acid ester is 80 to 10
Add 2 parts of one type that is above 0℃ and heat to 80-100℃
After digestion under heating, the fatty acid ester layer is separated,
An external preparation for skin, characterized in that it contains a soluble component of fatty acid ester of yellow oak obtained by standing still under freezing at around -20°C and then filtering. (2) The boiling point of the fatty acid ester is 80 to 10
After adding 2 parts of 1 type at 0°C or higher and digesting under heating at 80 to 100°C, the remaining yellow oak residue after separating the fatty acid ester layer was mixed with n-hexane or Immerse it in ether, transfer the fatty acid ester remaining in the residue into the solvent layer, separate the residue, and add water and propylene glycol or water and butylene to 1 part of the separated residue. Add 20 parts of a mixture with glycol in a 1:1 ratio, and make 8
After digestion under heating at 0 to 100°C, the liquid layer is taken out, left to stand under freezing at around -20°C, filtered, and the liquid layer is concentrated under reduced pressure. The obtained skin external preparation is characterized by containing a water-soluble component of Aspergillus orientalis. (3) Fatty acid ester having a boiling point of 80 to 100°C or higher relative to the residue after completely removing the solvent under reduced pressure from the eluted components transferred from Huang Bao using n-hexane or ether. After adding and dissolving under heating at 80 to 100°C,
After leaving it in the freezer at around minus 20 degrees Celsius, filter it.
Linoleic acid/sitosterol in the filtrate is 2.0~
A skin external preparation characterized by containing a fatty acid ester soluble component of Aspergillus orientalis , which is adjusted to contain 4.8%.