WO2006033473A1

WO2006033473A1 - Denatured silk and aqueous extract thereof

Info

Publication number: WO2006033473A1
Application number: PCT/JP2005/018064
Authority: WO
Inventors: Tadashi Komoto; Tatsuo Kumazaki; Masashi Horiguchi
Original assignee: Minekawa, Sumiko
Priority date: 2004-09-22
Filing date: 2005-09-22
Publication date: 2006-03-30
Also published as: JP4906509B2; JPWO2006033473A1

Abstract

Denatured silk is produced by heating silk in the state of being in contact with a solid surface. Then, this denatured silk is extracted with hot water to give an aqueous extract which is employed in cosmetic lotions, drugs, quasi drugs and so on. When applied to preparations and drugs, this extract remains colorless, transparent and odorless. Thus, silk protein can be degraded and cosmetics etc. having excellent qualities and functions can be provided.

Description

Meiji book Modified silk and its aqueous extract

The present invention comprises a modified silk, an aqueous solution of this modified silk, and an aqueous solution of the extracted silk, which contains no preservatives and is colorless and transparent without any deterioration such as decay even when stored at room temperature for a long time. It relates to tasteless, odorless cosmetics, pharmaceuticals and quasi drugs. Background art

Conventionally, various applications for silk cosmetics, foods, pharmaceuticals, medical materials, etc. have been studied (for example, Non-Patent Document 1). Actually, for example, silk powder is commercially available for cosmetics and foods. Surgical sutures made from silk hive mouth-in are used as medical materials.

Also, for example, silk hive mouth-in powder (Patent Document 2) obtained by dealkalizing, drying, and pulverizing an ice solution obtained by contacting silk thread with a hot alkaline aqueous solution is a raw material for skin lotion. . In addition, the raw silk is dissolved in an aqueous solution composed of calcium chloride, ethyl alcohol, and water, and then a mixed aqueous solution of hive mouth-in and sericin obtained by dialysis with water 10 times or more is cast, and the wound dressing (Method for producing silk film (Patent Document 3)) has also been proposed. However, the production of silk powder and silk film, which require such conventional chemical treatment, has a problem that requires many steps and time.

Furthermore, solids such as silk powder, sericin powder, silk thread, or silk film can be stored at room temperature, but the aqueous solution in which these are dissolved does not contain preservatives even when stored in glass containers. In this case, there is a problem that at room temperature, corruption starts in about two weeks. In addition, lotion using silk material is effective for whitening the skin and preventing aging. Toner lotions containing additives such as these are not preferred for the skin of allergic humans. Therefore, in the case of such a lotion made from conventional silk, it must be used within a short period of time or it must be added with a preservative. A storable silk extract or lotion was desired.

Therefore, many of the aqueous solutions from which silk cocoons, silk thread, silk powder, sericin powder, etc. are extracted are slightly yellow and have an odor peculiar to cocoons (unusual odor). The present inventor found that silk protein in the extracted aqueous solution is a cause of faint yellow color and off-flavor, and that it starts to rot by touching general bacteria in the air, or microorganisms remaining in the extraction process Studies have been conducted on the assumption that spoilage may begin when bacteria propagate using silk protein as a nutrient source.

In other words, the inventor of this application stated that the silk protein is a polymer having a molecular weight of several tens of thousands of Dal ton to several hundred thousand Dal ton and that the aqueous solution is spoiled. Assuming that there is a mechanism for recognizing protein as a nutrient source, the above problems can be solved if microorganisms and bacteria can be degraded and denatured, and silk protein can be degraded to lower the molecular weight. I thought that.

In addition, the silk protein extracted from silk has been reported to have medical effects such as anti-cancer activity (Non-patent Document 1), but the anti-oxidation effect and the aqueous solution of this high molecular weight silk protein have a slightly yellow color. There is a coloring, and there is a peculiar odor. Furthermore, as a non-negligible problem, high molecular weight proteins may cause anaphylactic uniform shocks when administered in vivo, which is problematic for use as a pharmaceutical product. If the inventor can denature microorganisms and bacteria contained in the cocoon and at the same time obtain a low molecular weight silk protein as described above, it is effective as a pharmaceutical or quasi-drug as well as lotion. Thought it would be excellent. As a result of the examination from the viewpoint as described above, the inventor firstly, The following was revealed. That is, when silk powder is produced by the chemical treatment as described above, or when silk is treated in water at a high temperature such as 120 for 30 minutes, the molecular weight generally decreases, but the molecular weight is about Since high molecular weight compounds of 5,000 ODalton or more are the main components (Patent Document 4), treatment in water has a limitation in molecular weight reduction, and in order to obtain only low molecular weight components, separation of components, etc. This requires a complicated process and has many problems.

Another method for obtaining low molecular weight materials is to pyrolyze silk without using an aqueous solution. Specifically, a method of reducing the molecular weight by oxidizing and decomposing silk in air can be considered. For example, as a means for heat-treating silk in the air, for example, a method (Patent Document 5) for treating in an atmosphere of air current having a temperature of 150 to 500 has been proposed. However, treatment under an air stream atmosphere requires a high heating temperature for the heat insulation effect of the air and requires a long time, but even under such severe conditions, the silk that constitutes many silks. There are various problems such as the fact that the protein is not decomposed and the high molecular weight component remains.

As a similar method, a method of heating silk at 300 to 700 on a frying pan has also been proposed (Patent Document 6). However, since silk is a temperature at which it is easy to burn, an optimal low molecular weight silk protein is proposed. There was a problem that it was inappropriate as a method for obtaining the above.

Non-Patent Document 1: Masakazu Nomura, Hideyuki Yamada, Unbreakable Junsei, Textile and Industry, 57, 10, 279 (200 1)

Patent Document 2: Japanese Patent No. 26 1 5440

Patent Document 3: Japanese Patent No. 2990239

Patent Document 4: Japanese Patent Laid-Open No. 2003-3 17 874

Patent Document 5: Japanese Patent No. 3066434

Patent Document 6: Japanese Patent Laid-Open No. 7-33062 1 Disclosure of the invention

The present invention eliminates the conventional problems from the background as described above, and has colorlessness, transparency, and odorlessness in the application to cosmetics such as lotion, or pharmaceuticals, and an antiseptic is added. Can be stored for a long period of time even if it is not, providing a new technical means that can reduce the molecular weight of silk protein and realize high-quality, superior cosmetics, pharmaceuticals, quasi-drugs, etc. The challenge is to do.

In order to solve the above-mentioned problems, the present invention is as follows. First, silk is in contact with a heated solid surface under air or an oxidative atmosphere, and is lower than 2 00 ^ and lower than 3 0 0 Provided is a modified silk characterized by being a modified silk obtained by heat treatment in a temperature range.

Second, there is provided a modified silk-extracted aqueous solution characterized by being obtained by extracting the modified silk with hot water in a temperature range of 60 to 140.

Thirdly, the present invention provides a modified silk extraction aqueous solution characterized in that the amount of the hot water is in a range of 5 times to 30 and 0.00 times by weight with respect to the modified silk.

Fourthly, the present invention provides a modified silk extraction aqueous solution characterized in that the non-volatile components in the modified silk extraction aqueous solution are contained in an amount of 5 ppm to l% by weight with respect to the entire aqueous solution.

Fifth, the non-volatile component is a low molecular weight polyamino acid having a molecular weight of 75 Dal ton or more and 3,00 Dal ton or less and comprising one or more amino acid residues, or a mixture of these low molecular weight polyamino acids. A modified silk extraction aqueous solution characterized by having a main component as a base.

Sixth, among the plurality of amino acid residues constituting the low molecular weight polyamino acid or the mixture of the low molecular weight polyamino acids which are the main components of the non-volatile component, at least a tryptophan residue as an essential component Is a modified silk extraction aqueous solution characterized by containing 0.1 to 50 mol% of proline and 0.5 to 40 mol% of proline residues. I will provide a.

Seventh, it consists of a low molecular weight polyamino acid composed of a plurality of amino acid residues having a molecular weight of 75 Dalton or more and 3,00 O Dal ton or a mixture of these low molecular weight polyamino acids, and at least tributophane as an amino acid residue. Containing 5 ppm to 1% by weight of low molecular weight polyamino acid components having residues of 0.1 to 50 mol% and proline residues of 0.5 to 40 mol% relative to the total amount An aqueous solution of a low molecular weight polyamino acid characterized by the above is provided.

Eighth, an external composition characterized in that any one of the above-mentioned modified silk extraction aqueous solutions is an active ingredient, and ninth, the low molecular weight polyamino acid aqueous solution is an active ingredient. A composition for external use is provided.

A tenth aspect provides a cosmetic or medicinal cosmetic characterized in that it is the composition for external use.

In the first aspect, the present invention provides a cosmetic or medicinal cosmetic characterized in that it improves skin spots, wrinkles, dullness, dryness and sagging by application.

First, a pharmaceutical or quasi-drug for skin prescription characterized by being the above-mentioned composition for external use is provided.

The first is to provide a medicinal product or quasi-drug for skin prescription characterized in that application improves skin pimples, acne, and atopic dermatitis.

The first 14 is that the application improves skin cuts / scratches, pain, burns, itching, crotch, diaper rash, itching, insect bites, rashes, eczema, bed sores (pox), and hay fever. Pharmaceutical products or quasi-drugs for skin prescriptions characterized by BEST MODE FOR CARRYING OUT THE INVENTION

The present invention has the characteristics as described above. The embodiment will be described in detail.

First, in the present invention, as silk, liquid silk produced by cocoon or dried product thereof, cocoon, cocoon feather, silk wool, scoured silk, silk thread, silk sericin and silk fiber mouth-in which are cocoon ingredients, or these The recycled material is exemplified as a suitable target, and silk cotton is more preferable in terms of quality and handling.

In addition, the seeds of silkworms that produce silk are not particularly limited, and examples include rabbits, cocoons, tensans, saksans, erisans, shijusans, and cussans.

The atmosphere for heat-treating the silk is not particularly limited as long as it is a gas containing oxygen, and may be an oxidative atmosphere such as air or a mixed gas of oxygen and an inert gas, and is air. More preferred. The solid surface for heat-treating silk with heat treatment in contact with the heated solid surface is not particularly limited as long as the material on the solid surface is a heat-resistant material that does not generate thermal decomposition products. Metals such as iron, steel, copper, and aluminum, ceramics, their fluororesin coatings, and heat-resistant glass are preferable as materials, and more preferably metal. The shape is not particularly limited as long as silk can be heated and brought into contact with the surface in an oxidizing atmosphere, and flat plates, flat-bottom containers, and round-bottom containers are preferably considered.

The means for heating the solid is not particularly limited as long as it is a heat source that can heat the solid from the bottom, and a gas heater or an electric heater is preferable.

The state in which silk is in contact with such a heated solid surface means that at least a part of each silk as a filament or the like only needs to contact the solid surface. This contact may be all or part of the heat treatment time. What is important is that the silk is heated and decomposed by oxidation in a lower temperature range of 200 to 300. When the silk is oxidized in contact with the heated solid surface, the temperature for obtaining the desired modified silk is lower than when the silk is simply oxidized under an air stream as in the conventional method. be able to. Therefore, it can be set to a temperature range of 2 0 0 or more and lower than 3 0 0 · Ό. This temperature range is actually set as the temperature near the surface of the solid or in contact with the silk. More preferably, it is in the range of 2 5 O ^ C or more and lower than 30, and most preferably 2 70 or more and 2 95 or less.

In addition, when compared at the same temperature, it is advantageous to oxidize silk while in contact with a heated solid surface, which shortens the heating time for obtaining the desired modified silk than simply oxidizing under an air stream. There is. Since silk material is relatively bulky, when it is oxidatively decomposed in large quantities, it takes a longer time to sufficiently bring all fine silk fibers into contact with the solid surface. On the other hand, if the oxidation reaction is performed with a sufficiently wide contact area with respect to the amount of silk fibers, that is, if the amount of silk per contact area is small, the reaction can be completed in a short time. However, since the oxidation reaction rate decreases as the solid surface temperature decreases, the reaction time must be increased as the solid surface temperature decreases. Therefore, in consideration of productivity, the reaction time is preferably 30 seconds or more and 6 hours or less, more preferably 5 minutes or more and 3 hours or less, and 10 minutes More preferably within 2 hours.

In order to extract only silk protein from the silk modified product obtained by oxidative decomposition in this way, Al force does not contain additives such as harmful heavy metal ions, and the concentration of microorganisms and bacteria as drinking water The water is not particularly limited as long as it is below the standard value. Of these, almost neutral water such as distilled water, ion exchange water, tap water, and drinking water is preferably used. Furthermore, for the purpose of removing impurities and the like in the extracted aqueous solution, it is more preferable to coexist with activated carbon and charcoal, and it is most preferable to use water in which Bincho charcoal coexists. In order to extract silk protein from the modified silk, Since the extraction efficiency is high, a temperature range of 60 to 140 is preferable, a temperature range of 85 to 120 is more preferable, and a temperature range of 95 to 100 is most preferable in terms of productivity.

The amount of the water (hot water) for obtaining the modified silk-extracted aqueous solution is preferably in the range of 5 to 30,000 times by weight with respect to the modified silk, and 20 to 10 to 10, A range of 000 times is more preferable, and a range of 40 times to 5,000 times is most preferable.

The modified silk extract aqueous solution thus obtained can be used as it is in cosmetics and pharmaceuticals and quasi-drugs, but it can be filtered with filter paper in order to separate the charcoal coexisting during hot water extraction. It is preferable to filter.

Since the concentration of silk protein in the modified silk extraction aqueous solution, which is the filtrate after being extracted from the modified silk with hot water, depends on the amount ratio of the modified silk and water, The concentration of silk protein, which is the main component of the non-volatile component (amino acid component), is preferably 5 ppm to 1% with respect to the total weight of the aqueous solution, and 20 ρ ρπ! More preferably, it is ˜1%, 70 ρρπ! Most preferred is ~ 0.1%.

Furthermore, in order that the polyamino acid, which is a main component of the non-volatile component in the modified silk extract aqueous solution, does not cause changes such as decay even during long-term use, its molecular weight range is 75 Dalton or more. It is preferably 3,000 Dalton or less, more preferably 75 Dalton or more and 2,000 Dalton or less, and most preferably 75 Dalton or more and 1,500 Dalton or less.

In addition, the polyamino acid that is a main component of the non-volatile component is a low molecular weight polyamino acid obtained by heat-oxidizing and decomposing silk, and includes a plurality of amino acids constituting unmodified silk, but is used for a long time. As a protein that functions as a lotion, pharmaceuticals, and quasi-drugs, it does not cause changes such as spoilage. Among the groups, it is preferable that the essential components include 0.01 to 50 mol% of tribtophan residues and 0.5 to 40 mol% of proline residues, and 1 to 45 5 of tribtophan residues. More preferably, it contains 1 to 35 mol% of mol% and proline residues, and most preferably contains 5 to 40 mol% of tryptophan residues and 3 to 30 mol% of proline residues.

Regenerated silk, such as conventional regenerated hive-in and regenerated sericin, is a high molecular weight product with a molecular weight of tens of thousands of Dal tons, and the amino acid composition is not much different from the original fibroin or sericin. In addition, aqueous solutions prepared from these regenerated silks have a slightly yellow color and some have a peculiar odor. Furthermore, these aqueous solutions generate malodor associated with decay at room temperature in about 2 weeks, and at least without the addition of preservatives, they cannot be used as a raw material for skin lotions. There is a big problem in using it as a.

However, as described above, since the silk protein in the aqueous modified silk extract obtained in the present invention has a very specific molecular weight and amino acid composition, the modified silk extracted aqueous solution is Colorless, transparent, tasteless, odorless, and no degradation such as decay occurs at room temperature for long periods. Therefore, the modified silk-extracted aqueous solution can be used as it is in a cosmetic polyamic acid aqueous solution that does not require the addition of preservatives or the like, and it can be used as it is in cosmetics, as well as in pharmaceuticals, quasi drugs and the like.

In the present invention, as described above, a low molecular weight poly- mer composed of a plurality of amino acid residues having a molecular weight of 75 DaUon or more and 3,00 0 Dal ton or less is obtained as an aqueous solution that has never been known. Low molecular weight consisting of an amino acid or a mixture of these low molecular weight polyamino acids and having at least 0.5 to 50 mol% of tributophane residues and 0.5 to 40 mol% of proline residues as amino acid residues 5 p ρ π by weight of polyamino acid component based on the total amount! Contain ~ 1% The characteristic low molecular weight polyamino acid aqueous solution will be provided. In the present invention, the modified silk extract aqueous solution and the low molecular weight polyamino acid aqueous solution as described above can be used as the active ingredients of the composition for external use.

For example, it is a composition for external use as cosmetics, medicinal cosmetics, pharmaceuticals, and quasi drugs. Cosmetic, medicinal cosmetics, or quasi-drug forms include, for example, lotions, lotions, emulsions, creams, lotions, jewels, sprays, cleansing agents, rinses, packs, conditioners, and foundations. It is used as various forms. Other ingredients may be added as needed.

However, it is emphasized that the aqueous solution of the present invention has a great feature that it can be used as it is as a lotion or a cosmetic liquid.

In addition to the above-mentioned various forms, it is also used as a soft corn, puppy, etc. in pharmaceutical products as a skin prescription.

For example, when the aqueous solution is used as a skin lotion, the container filled with the skin lotion is particularly limited as long as the material component of the container does not elute into water and does not change color or deteriorate over a long period of time. It may be made of glass or resin, but a glass container is more preferred.

The above-mentioned lotion can be used to improve skin blemishes, dullness, dryness, and sagging by application, as well as skin pimples, acne, atopic dermatitis, cuts, abrasions, pain, burns. It can be used as a medicine or quasi-drug that has the effect of reducing, itchiness, crotch, diaper rash, tingling, insect bite, rash, eczema, bed sores (decubitus), hay fever, and healing. it can. Hereinafter, examples will be shown, and the embodiments of the present invention will be described in more detail. Of course, the present invention is not limited to the following examples, and it goes without saying that various aspects are possible in detail. Yes.

<1> Preparation of modified silk and modified silk aqueous extract

Example

Example 1

The surface of a clean iron plate heated by a gas heater was brought into contact with 5 g of silk cotton for 13 minutes in the presence of air at 29 to obtain 3.2 g of modified silk.

Add 700 mL of distilled water (700 times the weight ratio to the modified silk) and 1 g of the modified silk and 2 g of Bincho charcoal into a glass round bottom flask with a clean surface, attach a reflux condenser, and add an electric heater ( The mantle was boiled for 2 hours. The obtained hot aqueous solution was filtered using No. 2 filter paper manufactured by Advante, and cooled to room temperature to obtain a colorless, transparent, tasteless, odorless modified silk extraction aqueous solution. The weight of the modified silk residue after extraction was 3.1 g.

Example 2

3.3 g of modified silk was obtained in the same manner as in Example 1 except that the heating temperature was 270 and the heating time was 70 minutes.

Furthermore, a colorless, transparent, tasteless, and odorless modified silk extraction aqueous solution was obtained in the same manner as in Example 1 except that the hot water extraction time was 3 hours. The weight of the modified silk residue after extraction was 3.2 g.

Example 3

3.3 g of modified silk was obtained in the same manner as in Example 1, except that the heating temperature was 250 and the reaction time was 120 minutes.

Furthermore, by the same operation as in Example 1, a colorless, transparent, tasteless, and odorless modified silk extraction aqueous solution was obtained. The weight of the modified silk residue after extraction was 3.2.

From the above results, it was found that when the heating temperature is low, a good modified silk and a modified silk-extracted aqueous solution can be obtained by a long-time reaction. Comparative Example 1

Except that the heating temperature was 3 10, the silk wool was subjected to an oxidation reaction in the same manner as in Example 1. As a result, the silk cotton burned within 1 minute, and the remaining weight of the silk cotton became 0 g. I couldn't get silk. Therefore, it was not possible to obtain a modified silk extract aqueous solution under these conditions. Comparative Example 2

Except that the heating temperature was 180 and the heating time was 12 hours, the silk silk was oxidized by the same operation as in Example 1. As a result, the weight of the silk silk after the reaction was 4.3 g. Yes, the weight loss of silk cotton was 14%, which was lower than that of Example 1, and no modified silk similar to Examples 1 to 3 was obtained. The silk aqueous cotton after this oxidation reaction was prepared as an extraction aqueous solution in the same manner as in Example 1. As a result, the aqueous solution had a yellow color and had a peculiar odor of wrinkles. Was found to be unsuitable.

Based on this result, under the conditions where the oxidation reaction rate is even slower, 1800, even if the reaction time is increased to 12 hours, part of the silk cotton remains unmodified, colorless, transparent, tasteless It became clear that an odorless modified silk aqueous solution could not be obtained. 2> Room temperature storage stability of modified silk extract aqueous solution

Example 4

The modified silk-extracted aqueous solution obtained in Example 1 (10 O mL) is filled in a cleaned glass container (capacity: 103 mL) with a screw cap, sealed, and stored at room temperature for 1 year. The modified silk extract aqueous solution was colorless, transparent, tasteless, odorless, and no deterioration such as decay occurred.

Further, as described later, for the purpose of using the modified silk extract aqueous solution for skin lotion, etc., the modified silk extract aqueous solution 10 O mL is filled in a cleaned glass container with a screw cap in the same manner as described above. Once a day, the cap was opened, and after applying a few drops of the extracted aqueous solution to the skin, the cap was closed for 6 months. Also in this case, The solution did not change in quality and was colorless, transparent, tasteless and odorless.

Example 5

Except that the modified silk obtained in Example 2 was used, the room temperature storage stability of the modified silk extract aqueous solution was examined in the same manner as in Example 4. As a result, as in Example 4, even if the glass container was stored in a sealed state for 1 year, and the opening and closing were repeated for 6 months, the extracted aqueous solution did not change in quality, and no coloration occurred. It was clear, tasteless and odorless.

Comparative Example 3

Each of the extracted aqueous solutions having a yellow and off-flavor obtained in Comparative Example 2 was stored at room temperature for 3 months in the same manner as in Example 4. However, the yellow and off-flavor remained and may not be suitable for use in skin lotions. confirmed.

Analysis of non-volatile components of <3> modified silk extract aqueous solution

Example 6

In order to measure the concentration of non-volatile components in the modified silk extract aqueous solution obtained in Example 1, a freeze dryer (Iwaki Freeze Dryer FRD-50M) was used, and the modified silk extract aqueous solution 10 O m was used. L was freeze-dried to obtain 18 mg of solid powder. As a result, it was revealed that the concentration of the non-volatile component in the modified silk extract aqueous solution was 180 ppm.

Next, amino acid analysis of the solid powder as a non-volatile component was performed by the following method. Weigh 2.65 mg of the above solid powder into a glass test tube, add 10 L of 6 N hydrochloric acid, hydrolyze it with 110 for 22 hours to decompose to the amino acid monomer, and then dry under reduced pressure. Solidified. The obtained residue was dissolved in 100 L of purified water and filtered through a 0.22 tm filter to obtain a filtrate.

50 L of the filtrate was subjected to amino acid analysis. Amino acid analysis was performed by a ninhydrin color development method using a Hitachi-8500 type amino acid analyzer. Each amino acid in the chromatogram of the sample obtained in the amino acid analysis is the same as the chromatogram of various amino acid standard products. Set.

As a result, as shown in Table 1, it was clarified that the main component of the non-volatile component was an amino acid compound (low molecular weight polyamino acid as described later). Surprisingly, 33.4 3 mol% of triftophan and 2 8 74 4% of proline are contained in all amino acids constituting the main component of the non-volatile component. This is one of the features of the present invention. Although glycine is also contained in 18.666%, it can be said that dalycin is an appropriate content considering that it is an amino acid that is naturally contained in silk fibroin and silk sericin.

One of the objects of the present invention is to reduce the molecular weight of silk protein by oxidative degradation. Therefore, the molecular weight measurement of the main components of the above non-volatile components was performed using the mass spectrometer Voyager Sys tem 6 manufactured by Applied Biosys tems. 2600, £ x-Cyano-4-hydroxycinnamic acid as calibration matrix, angiotensin (molecular weight 1, 26 SDalton) as reference material for molecular weight measurement, and Voyager Biospector ometry Workstation This was performed using Ver.5.0.

As a result, it has been clarified that the main component of the above non-volatile component is a mixture of low molecular weight polyamino acids having a maximum molecular weight of 1,50 ODalton or less. That is, the inventors of the present application succeeded in obtaining a low molecular weight polyamino acid that could not be obtained by a conventional method. In addition, the modified silk extract aqueous solution according to the present invention is an aqueous solution of a mixture of low molecular weight polyamino acids containing a large amount of tributofan and proline, and is colorless, transparent, tasteless, and odorless that cannot be obtained with conventional silk extracts. It is concluded that this is an aqueous solution characterized by being stored at room temperature for a long time without deterioration such as decay. 4> Skin irritation of modified silk extract aqueous solution

Example 7

3 A modified silk extract aqueous solution obtained in Example 1 according to the method described in Example 4 for 10 men and women with healthy skin from 5 to 6 years of age. 10 OmL Filled a cleaned glass container with a screw cap, opened the cap twice a day, applied a few drops of the above aqueous extract solution to the skin of the hands and arms, and then closed the cap for 2 months. The skin irritation of the modified silk extract aqueous solution was examined.

As a result, there was no irritation or rough skin on the skin of all 10 monitors, but rather, the skin became smooth and moist.

<5> Effect of Modified Silk Extraction Aqueous Solution on Skin Blots, Wrinkles, Dullness, Dryness, and Sagging As described in Example 7, the modified silk extract aqueous solution of the present invention has no skin irritation or rough skin. Rather, it has become clear that it improves the properties of the skin. The purpose of this study was to examine skin spots, dullness, dryness, and sagging. The results are shown in Table 2, and will be described in detail in Examples 8 to 12.

Example 8

3 Male and female with healthy skin from 5 to 5 years old 7 For 4 monitors, the cotton impregnated with the modified silk extract aqueous solution obtained in Example 1 every day, at least twice in the morning and evening, face It was pressed against the spotted area for 5 minutes and the change in the spot was observed.

As a result, the faint blots faded to an unacceptable level 7 days or 1 month after the start of the test, and in the case of dark blots, they almost disappeared in 1 to 6 months. 7 Out of 4 monitors 7 2 people no longer lose or disappear. The other two monitors were excluded from the data that they were effective because the use of the modified silk extract aqueous solution was stopped several days after the start of the test.

Thus, since the modified silk extract aqueous solution of the present invention has the effect of eliminating the stain and giving beautiful skin, most monitors continued to be used even after the stain disappeared. 1 After the disappearance of the stain, the 3 monitors stopped applying to the spot, but no recurrence of the stain was observed for at least 6 months.

Example 9

3 About 9 6 men and women with healthy skin from 3 to 5 years of age 9 As with Example δ, a cotton with a modified silk extraction water solution was applied to the wrinkled part of the face. Each day, they were pressed at least twice in the morning and evening for 5 minutes each to observe wrinkle changes.

As a result, fine lines in the corners of the eyes and fine lines in the mouth are not noticeable about one month after the start of the test, and even a relatively deep wrinkle is noticeable in several months. One person was recognized. The other five monitors were excluded from the data that would have been effective for the same reason as in Example 8. Also, as in Example 8, most monitors continued to use the modified silk extract aqueous solution after the disappearance of fine lines. For the two monitors, the use of the modified silk extract aqueous solution was stopped, but no noticeable fine lines were observed until at least 6 months after the use was stopped.

Example 1 0

3 Men and women with healthy skin from 5 to 5 years of age 1 1 0 Monitor for one person Similar to Example 8, a dipped part of face with dull silk extracted with a modified silk solution. Tons were pressed every day, at least twice in the morning and evening, for 5 minutes each to observe changes in dullness.

As a result, 1 0 9 out of 1 10 monitors showed a noticeable effect that facial dullness disappeared in 1 day at the earliest time after the start of the study, and disappeared after 1 or 2 weeks even at a later time. It was. The other one monitor was excluded from the data that would have been effective for the same reason as in Example 8.

Also, as in Example 8 and Example 9, I was impressed by the surprising effect of the modified silk extract aqueous solution of the present invention, and the coating was continued even after most monitors disappeared.

For the three monitors that stopped application after the disappearance of dullness, dullness did not recur until at least 6 months after discontinuation of use. Example 1 1

3 From 5 to 5 years of age, the skin is bulky and moisturized so-called dry skin men and women 9 For 7 monitors, as in Example 8, on the dry skin of the face and limbs The cocoon soaked with the silk extract aqueous solution was pressed every day at least twice in the morning and evening for 5 minutes each to observe changes in the skin condition.

As a result, a significant change was observed in dry skin in 1 day at the earliest time after the start of the test, and after 1 to 2 weeks even at the later time, 9 5 out of 9 monitors. Recognized by The other two monitors are effective for the same reason as in Example 8. Excluded from the data.

Further, as in Examples 8 to 10, most monitors continued to use the modified silk extract aqueous solution even after the skin became moist. For the 8 monitors who stopped using the modified silk extract aqueous solution after a moist feeling was achieved, there was no recurrence of bulky skin symptoms until at least 6 months after cessation of use.

Example 1 2

3 Men and women aged 8 to 5 9 years 9 For two monitors, as in Example 8, in particular, at least morning and evening, cotton with a modified silk extraction aqueous solution in the part of the heel where slack is likely to occur. Pressed twice for 5 minutes each and observed changes in the sagging slack.

As a result, it was found that the sagging of the heels became a tight and firm skin about one month after the start of the test. 9 Out of 2 monitors 8 7 had good results. The other five monitors were excluded from the data that would have been effective for the same reason as in Example 8.

In addition, as in Examples 8 to 11, most monitors continued to use the modified silk-extracted aqueous solution even after a tight tensioned state was obtained. After the wrinkle sag was resolved, the four monitors who stopped using the modified silk extract aqueous solution showed no recurrence of wrinkle sag until at least 3 months after cessation of use.

<6> Effect of modified silk extract aqueous solution on skin pimples, acne, and atopic dermatitis As described above, the modified silk extract aqueous solution of the present invention was found to have a remarkable effect on skin properties. Therefore, the effects of the modified silk extract aqueous solution on skin pimples, acne, and atopic dermatitis were investigated for the purpose of use as a skin lotion, pharmaceuticals, and quasi drugs. The results are shown in Table 2, and these effects will be described in detail in Examples 13 to 15. Example 1 3

3 Male and female aged 0 to 5 8 5 For 9 monitors, as in Example 8, daily cotton at least morning and evening 2 Pressed each time for 5 minutes to observe the state change of the breakout.

As a result, the pimple was found to be in good condition within a few days to about 2 weeks after the start of the test. 5 out of 9 monitors 5 7 showed healing effects of breakouts. Of the other two monitors, one was excluded from the data that would have been effective for the same reason as in Example 8. The remaining 1 person did not see any effect after 2 weeks of testing.

Even when the use of the modified silk extract aqueous solution was stopped, it was not observed that the exudate recurred at the same site until at least 2 months after healing.

Example 1 4

1 Males and females aged 2 to 30 years 7 For 9 monitors, as in Example 8, each day, a cotton impregnated with a modified silk extract aqueous solution is applied at least twice a day in the morning and evening. Press for 5 minutes and observe the change in acne condition.

As a result, it was found that acne began to decrease within a few days after the start of the test and was in good condition in about one month. 7 Out of 9 monitors 7 6 were effective. Of the other three monitors, two were excluded from the data that would have been effective for the same reason as in Example 8. The remaining one did not show a noticeable effect even after the 2-week study.

Most of the monitors are in good condition about 1 month after the start of the test, and even if acne is not noticeable, acne scars disappear completely from the face, and it is difficult to completely cure the skin without any acne. Continued to use the modified silk extract aqueous solution daily. Example 1 5

Applying a modified silk extract aqueous solution to the affected area daily, at least twice in the morning and evening, for 5 minutes each, for the monitor of 9 6 men and women with atopic dermatitis from 5 to 5 to 7 years of age, as in Example 8. We observed changes in the state of atopic dermatitis.

As a result, it was found that itching was reduced in a short time after the start of the study in a slightly reddish affected area, and it became good after 1 to 3 weeks. In addition, even in the affected area with severe symptoms with dripping skin, the symptoms improved significantly within 6 months. 9 9 out of 6 monitors 9 3 were cured or markedly improved. Of the other three monitors, two were excluded from the data that they were effective for the same reason as in Example 8. The remaining 1 person did not improve after 2 weeks of testing.

As in the case of Nikipi in Example 14, most monitors continued to use the modified silk extract aqueous solution daily after the symptoms of atopic dermatitis improved.

<7> Skin cuts / scratches, pain, burns, itching, crotch slipper, diaper rash, scab, insect bite, rash, eczema, bed sores (decubitus), pollen allergy Since the modified silk extract aqueous solution of the present invention has been found to have various effects not only for skin lotions but also for pharmaceuticals and quasi drugs, it has not been found in conventional cosmetics using silk. The effects of other skin diseases were also examined. The results are shown in Table 2, and these effects will be described in detail in Examples 16 to 25.

Example 1 6

3 Male and female from 0 to 60 years old 3 For 7 monitors, apply the modified silk extract aqueous solution of the present invention to the wound of minor cuts and scratches caused by injury in daily life, or Example 8 In the same way, press a cotton or tissue dyed with a modified silk extraction aqueous solution for about 5 minutes. The wound was observed for changes in state.

As a result, in the case of mild wounds, a certain amount of pain occurred, but all monitors stopped feeling pain in about 1 minute just by applying the modified silk extract aqueous solution. Furthermore, when the denatured silk extract aqueous solution was applied, or the cotton or Tissyu soaked with this was continuously applied every day, the wound did not become suppurated in all monitors, and 4 days to Healed in 7 days, especially in the case of scratches, and it was found that the wound recovered quickly. 3 out of 7 monitors 3 All 7 were effective.

For all monitors, after the wound was recovered, the use of the modified silk extraction aqueous solution was stopped, but it did not deteriorate at all.

Example 1 7

3 Male and female from 3 to 5 years old 3 For 4 monitors, the same as in Example 1-6, but with a modified silk extract aqueous solution soaked in the area of mild burns that occurred in daily life The effect was investigated by pressing the noodles or Tissyu for about 5 minutes.

As a result, burns are generally more painful and last longer than cuts and scratches, but all monitors are painful in about 1 minute by applying the modified silk extract aqueous solution of the present invention to the affected area of mild burns. I felt no longer. Furthermore, when the modified silk extract aqueous solution was applied or the cotton or tissue soaked with this was continuously applied every day, 7 days to 1 month without any suppuration of the affected area in all monitors. It became clear that healed. 3 Effectiveness was observed for all four monitors. Of course, even after application of the modified silk extract aqueous solution was stopped after healing, it did not deteriorate at all.

Also, for the two monitors that had burned in the past and left burn marks (including one burn on the palm and the other on the back of the hand) for 6 months, as in Example 8. Using the modified silk extract aqueous solution as a burn mark When pressed, the surprising result was that it recovered to healthy skin.

Example 1 8

In Example 15, it was confirmed that the itchy skin dermatitis was reduced by applying the modified silk extract aqueous solution of the present invention to the affected area. In order to investigate the effect of the modified silk extract aqueous solution on itching caused by insect bites etc. in other daily life, about 10 8 males and females from 30 to 5 9 years old, the affected area of itch A modified silk extract aqueous solution was applied, and the part was rubbed with a finger several times so that the modified silk aqueous solution penetrated into the skin, and the change in itching was examined.

As a result, mild itching disappeared in about 1 minute after application. In addition, even when itching was caused by scouring the skin before applying the modified silk extract aqueous solution, itching disappeared in about 10 minutes, but as in Example 8, 2 The affected area was restored to healthy skin by pressing the modified silk extract aqueous solution against the affected area for a week or 1 month. The effect was recognized in 1 0 6 out of 10 8 monitors. The other two monitors were excluded from the data that they were effective because no responses were obtained.

Example 1 9

Crying due to crotch and / or diaper rash pain For five infants aged 0 to 1 year, as in Example 8, the modified silk extraction aqueous solution of the present invention was pressed against the affected area to change the symptoms. Examined.

As a result, as in Examples 16 and 18, pain due to crotch slip and diaper rash was greatly reduced in about 1 minute after application of the modified silk extract aqueous solution, so that all infants stopped crying. It was. After that, the redness caused by crotch slip and diaper rash disappeared in 2 to 3 days by continuing the application, and all were completely cured. Even if the application was stopped after complete cure, no crotch slip or diaper rash occurred for about a week. Example 2 0. 3 For male and female monitors with chilli symptoms from age 0 to 5 years old 3 In the same manner as in Example 8, the modified silk extract aqueous solution of the present invention was pressed against the affected area to change the symptoms. Examined.

As a result, mild redness became healthy skin in 2 to 3 days after application of the modified silk extract aqueous solution. Even in the case of a slight bruise, the skin became healthy 4 to 7 days after application. 3 The effect was recognized by all 2 people.

Example 2 1

3 For 8 to 8 years old male and female insects from 5 to 5 years old, as in Example 1 8, apply the modified silk extract aqueous solution of the present invention to the affected area to observe the change in symptoms. Examined.

As a result, as described in Example 18, itching from insect bites is not felt in about 1 minute after application of the modified silk extract aqueous solution, and the affected area becomes healthy skin in 3 days to 10 days. became. 3 Effectiveness was observed in all 8 people. After complete cure, even if the application was stopped, the skin where the insect was bitten was naturally in a healthy state.

Example 2 2

As with Example 8, the monitor of two or three men and women with a symptom symptom from 0 to 5 to 5 years of age was examined by applying the modified silk extract aqueous solution of the present invention to the affected area and examining the change in symptoms.

As a result, ashmo healed in 7 to 10 days after application of the modified silk extract aqueous solution.

If sweat occurs continuously, it may not be completely cured, and only 2 out of 2 people were cured. For the other 3 monitors, 3 monitors were excluded from the data that would have been effective since the use of the modified silk extract aqueous solution was stopped several days after the start of the test, as in Example 8. did.

Example 2 3

3 Men and women with eczema on their skin from age 0 to 5 8 years 4 Moni of 8 people Example

In the same manner as in 8, the modified silk extract aqueous solution of the present invention was pressed against the affected area, and the change in symptom was examined.

As a result, eczema healed in 3 to 7 days after application of the modified silk extract aqueous solution in 39 out of 48 monitors. Of the other 9 people, 2 monitors were excluded from the data that had the same effect as in Example 8.

Example 2 4

5 2 to 6 3 years old 2-7 men and women with bedsores In the same manner as in Example 8, the modified silk extract aqueous solution of the present invention was pressed against the affected area to examine changes in symptoms.

As a result, mild bedsores became healthy skin in 3 to 4 days after application of the modified silk extract aqueous solution. In one person, a part of the skin was a pressure ulcer close to necrosis, but after about 1 month of application, recovery to healthy skin was observed. 2 All 7 monitors were effective. Also, among the long-term bedridden monitors, the modified silk was applied once a day or once every 2 days after complete cure to a site where bed slippage was likely to occur. Extraction A bed recurrence was not observed only by applying an aqueous solution. Example 2 5

Three types of men and women from 5 to 5 to 7 years old who have any one of various hay fever 15 Spray the modified silk extract aqueous solution of the present invention into the nasal cavity for the change of symptoms Examined. As a result, sneezing peculiar to hay fever was reduced by several sprays, that is, the symptoms were greatly reduced in one day.

In addition, when the modified silk extract aqueous solution was instilled against the itching of the eyes, which is another symptom of hay fever, there was no irritation to the eyes and the itching was greatly reduced by one instillation. Furthermore, no side effects occurred at all, even after instillation every day for a week. From this result, it can be concluded that the modified silk extract aqueous solution of the present invention is effective as a hay fever therapeutic agent having no side effects even when administered to the eyes as well as the nasal cavity. All 15 monitors were found to be effective in reducing hay fever.

In addition, after the hay fever was alleviated, when the spray or the instillation of the modified silk extract aqueous solution was stopped, the symptoms tended to recur around 2 days. As a result, the symptoms were greatly reduced. Many of the over-the-counter hay fever medications are effective for early symptoms, but with continued use, the efficacy tends to decrease. However, in the modified silk extract aqueous solution of the present invention, it was confirmed that the effect was maintained even after continuous use.

Monitor Reduction / Healing Reduction / Healing Until recurrence Examples Symptoms

(Number of people) Period of time until (Number of people) Example 8 Blot 74 72 7 days to 6 months> 6 months Example 9 Wrinkle 96 91 1 to several months> 6 months Example 10 Dullness 110 109 1 day to 2 weeks> 6 months Example 11 Dry skin 97 95 1 day to 2 weeks> 3 months Example 12 Sagging 92 87 About 1 month> 3 months Example 13 Pimple 59 57 Days to 2 weeks yam Example 1 Acne 79 76 Days to 1 month ― Example 15 Atopic dermatitis 96 93 7 days to 6 months

Example 16 Cuts and abrasions 37 37 4-7 days

Examples 16, 17 Pain 71 71 1 minute Complete cure Example 1 7 Burn 34 34 7 days to 1 month a Example 18 Itching 108 106 1 to 10 minutes Higuchi Example 19 Crotch, diaper rash 5 5 2-3 days Approx. 7 days Example 20 Red snapper 32 32 2-3 days ― Example 21 Insect bite 38 38 3-10 days

Example 22 Ash also 23 12 7 to 10 days-Example 23 Eczema 48 39 3 to 7 days-Example 24 Bed sores 27 27 3 to 1 month-Example 25 Hay fever 15 15 1 to about 2 days

Industrial applicability

According to the present invention as described above, a method for oxidative degradation of silk and a modified silk by the method are provided.

In addition, the aqueous extract solution obtained from such modified silk is colorless, transparent, tasteless, odorless, and does not degenerate due to decay even when stored at room temperature for a long period of time. Furthermore, lotion, pharmaceuticals, pharmaceuticals Wide utility value as quasi-drugs.

Claims

The scope of the claims

1. A modified silk obtained by heat-treating silk in contact with a heated solid surface in air or in an oxidizing atmosphere at a temperature of 2 00 or higher and lower than 3 0 01. A modified silk characterized by being.

2. A modified silk-extracted aqueous solution obtained by subjecting the modified silk of claim 1 to extraction treatment with hot water in a temperature range of 60 to 14.

3. The modified silk extraction aqueous solution according to claim 2, wherein the amount of the hot water is in a range of 5 times to 30 000, 00 times by weight with respect to the modified silk.

4. The non-volatile component in the modified silk extract aqueous solution is 5 p ρπ by weight with respect to the entire aqueous solution! The modified silk-extracted aqueous solution according to claim 2 or 3, characterized by containing ~ 1%.

5. The non-volatile component having a molecular weight of 75 Dalton or more and 3,00 ODalton or less and comprising a low molecular weight polyamino acid composed of one or more amino acid residues or a mixture of these low molecular weight polyamino acids as a main component. 5. The modified silk extraction aqueous solution according to claim 4 characterized by the above.

6. Among the plurality of amino acid residues constituting the low molecular weight polyamino acid or the mixture of the low molecular weight polyamino acids, which is the main component of the non-volatile component, at least tributophan residue is 0.001 to 50 mol. 6. The modified silk-extracted aqueous solution according to claim 5, wherein the proline residue is contained in the range of 0.5 to 40 mol%.

7. A low molecular weight polyamino acid consisting of a plurality of amino acid residues or a mixture of these low molecular weight polyamino acids having a molecular weight of 7 5 Dalton or more and 3, 00 0 Dalton or less, and at least triftophan residues as amino acid residues It is characterized by containing 5 ppm to 1% by weight of a low molecular weight polyamisoic acid component having an amount of 0.1 to 50 mol% and a proline residue of 0.5 to 40 mol% based on the total amount. Low molecular weight polyamino acid aqueous solution.

8. A composition for external use characterized by comprising the modified silk extract aqueous solution according to any one of claims 2 to 6 as an effective component.

9. A composition for external use comprising the low molecular weight polyamino acid aqueous solution according to claim 7 as an active ingredient.

1 0. Cosmetic or medicinal cosmetic product characterized in that it is a composition for external use according to claim 8 or 9 o

1 1. The cosmetic or medicinal cosmetic according to claim 10, wherein the application to the skin improves skin spots, wrinkles, dullness, dryness and sagging.

1 2. A pharmaceutical or quasi drug for skin prescription characterized by being an external composition according to claim 8 or 9.

13. The skin treatment medicine or quasi-drug according to claim 12, wherein skin exudates, acne, and atopic dermatitis are improved by application to the skin.

1 4. It is characterized by the improvement of skin cuts, abrasions, pain, burns, itching, crotch, diaper rash, scab, insect bite, eczema, bed sores (decubitus) and hay fever. The medicinal product for skin prescription and quasi-drug according to claim 12.