JP4048218B2 - Textile products with allergen decomposition function - Google Patents

Description

  The present invention relates to a fiber product formed from a fiber material carrying a drug capable of decomposing allergen using a metal phthalocyanine derivative as an effective main component.

  Allergic symptoms are caused when the allergen enters the human body through the skin, respiratory organs, or digestive organs, and is induced by an antigen-antibody reaction inherent in humans, releasing chemical mediators such as histamine and leukotriene in the body, Due to the generation of active oxygen, secondary symptoms may include fever, rash, pruritus, vomiting, rhinitis, etc. Such allergic symptoms develop depending on the combination of the type of allergen and the constitution of each individual human.

  Allergens are included as ingredients such as mites, their carcasses and excrement, pollen such as cedar, ragweed and camo, bacteria, fungi, eggs, milk, fish shellfish, soybeans, insects, animal hair, beast and human dander. , Many are proteins. In the current situation where there are no medications that are effective for allergic symptoms, it is important to keep allergens away from humans with allergic constitutions in order to prevent allergic symptoms. However, because allergens exist in nature and may be associated with things that are indispensable for human life, it is extremely difficult to remove them entirely from the sphere of living and is virtually impossible. It is.

  As a means for removing the generated allergen, Patent Document 1 discloses an anti-allergen filter. Tea polyphenol, which is a tea extract component, is attached to the filter as an allergy inactive agent. Patent Document 2 discloses anti-allergen fibers such as cotton, hemp, wool, silk, rayon, nylon, polyester, and acrylic containing a zirconium salt that reacts with and deactivates allergens, and bedding, masks, curtains, and the like. Textile products are shown.

  Further, an anti-mite treatment is known as a means for controlling mites of textile products. Anti-mite agents can only be expected to have a repellent effect in a small amount, and it is necessary to use a large amount in order to kill ticks, and the amount used is limited in terms of safety to humans. Moreover, the mite-preventing agent has no inhibitory effect on allergic symptoms caused by mite-derived allergens such as mite carcasses and excreta.

  Waterfowl feather products are widely used as materials for bedding and clothing because they are excellent in heat retention, moisture retention and breathability. Feather products are animal protein feathers that feed on ticks, absorb moisture due to human sweating, etc., and are warmed appropriately by human body temperature, creating an environment where ticks grow. Therefore, the amount of mite-derived allergen tends to increase remarkably. There are no known anti-allergen feathers that are not treated with an acaricide, are safe and have the effect of adsorbing mite-derived allergens.

  On the other hand, Patent Document 3 and Patent Document 4 disclose deodorants containing metal phthalocyanine as an active ingredient. Patent Document 4 describes that a metal phthalocyanine derivative acts as a redox catalyst and exhibits an effect as a deodorant.

JP 2000-5553 A JP 2001-214367 A JP 56-63355 A JP-A-61-258806

  The inventors of the present invention have studied the enzyme-like catalytic action of metal phthalocyanine for many years and have found that the protein is denatured by its adsorptivity and redox catalytic function. In view of the fact that it is extremely difficult to completely remove allergen generation, an object of the present invention is to provide a fiber product having an allergen decomposing function using such properties of metal phthalocyanine.

（式（Ｉ）中、ＭはＦｅ、Ｃｏ、Ｍｎ、Ｔｉ、Ｖ、Ｎｉ、Ｃｕ、Ｚｎ、Ｍｏ、Ｗ、Ｏｓから選択される金属）で示される金属フタロシアニンの誘導体を有効成分に含むダニ由来のアレルゲン分解剤が担持されている天然繊維、合成繊維、半合成繊維または再生繊維を含む綿、糸、織布、不織布、編物、または紙からなるアレルゲン分解繊維素材を少なくとも一部に有して、寝具、衣類、布団、カーテン、壁紙、またはカーペットに形づくられていることを特徴とする。 The problems allergen content fibrillation維製article according to claim 1 for solving the following formula (I)

(In formula (I), M Fe, Co, Mn, Ti, V, Ni, Cu, Zn, Mo, W, a metal selected from Os) from ticks including derivatives of metal phthalocyanine represented by the active ingredient At least a part of an allergen-degrading fiber material made of cotton, yarn, woven fabric, non-woven fabric, knitted fabric, or paper containing natural fibers, synthetic fibers, semi-synthetic fibers or regenerated fibers carrying the allergen-degrading agent of It is characterized by being shaped into bedding, clothing, bedding, curtains, wallpaper, or carpet .

（式（ＩＩ）中、ＭはＦｅ、Ｃｏ、ＣｕおよびＮｉから選択される金属、Ｒ^１、Ｒ^２、Ｒ^３およびＲ^４は同一または異なるＣＯＯＨ基またはＳＯ_３Ｈ基であり、ｎ１、ｎ２、ｎ３およびｎ４は０〜４で１≦ｎ１＋ｎ２＋ｎ３＋ｎ４≦８を満たす正数）で示される化合物、またはその塩であることを特徴とする。 Allergen content fibrillation維製article according to claim 2, comprising the configuration described in claim 1, a derivative of the metal phthalocyanine is represented by the following formula (II)

(In the formula (II), M is a metal selected from Fe, Co, Cu and Ni, R ¹ , R ² , R ³ and R ⁴ are the same or different COOH groups or SO ₃ H groups, and n1, n2 , N3 and n4 are 0 to 4 and a positive number satisfying 1 ≦ n1 + n2 + n3 + n4 ≦ 8), or a salt thereof.

  Derivatives of metal phthalocyanines, which are active ingredients of allergen-degrading agents, coordinate allergen proteins to the central metal and cleave peptide bonds by oxygen oxidation in the air, thus reducing the molecular weight and changing the molecular structure. Or Derivatives of metal phthalocyanines not only simply adsorb allergens, but also act as decomposition catalysts, so their action is permanent. Allergens invade the human body, and due to their molecular structure, they specifically bind to human antibodies and show allergic symptoms, but if the allergen is low molecular or the molecular structure of the allergen is changed, It does not bind to previously reacted antibodies.

  Allergens in the living environment are mostly decomposed by this degrading agent, and even if a small amount of residue enters the human body having an allergic constitution, the concentration does not reach the threshold for developing allergic symptoms. Therefore, if an allergen degrading agent is placed in the living environment, even a person with an allergic constitution can lead daily life without developing symptoms.

  Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to the following examples.

  The allergen decomposing agent is a metal phthalocyanine dicarboxylic acid, metal phthalocyanine tetracarboxylic acid, metal phthalocyanine octacarboxylic acid, metal phthalocyanine disulfonic acid, metal phthalocyanine tetrasulfonic acid, metal phthalocyanine octasulfonic acid, or these acids. It is preferable that it is a salt.

The structural formula of metal phthalocyanine dicarboxylic acid is represented by the following formula (III)

The structural formula of metal phthalocyanine tetracarboxylic acid is represented by the following formula (IV)

The structural formula of metal phthalocyanine octacarboxylic acid is the following formula (V)

The structural formula of metal phthalocyanine disulfonic acid is represented by the following formula (VI)

The structural formula of metal phthalocyanine tetrasulfonic acid is the following formula (VII)

で例示される。 The structural formula of metal phthalocyanine octasulfonic acid is the following formula (VIII)

It is illustrated by.

  The allergen decomposing agent and the allergen decomposing method will be described.

  The allergen degrading agent contains a derivative of the metal phthalocyanine represented by the formula (I) as an active ingredient, and M is selected from the metals described above. Among them, Fe, Co, or Cu is preferable. Most preferred is iron phthalocyanine tetracarboxylic acid.

  The metal phthalocyanine compound of formula (II) or a salt thereof may be commercially available or may be produced by a known method. For example, it can be produced by the method described in "Phthalocyanine -Chemistry and Function-" (by Shigei Yoshiyoshi and Kobayashi Nagao, IP Publishing Co., Ltd., issued on February 28, 1997). For example, iron phthalocyanine tetracarboxylic acid can be obtained as follows. Trimellitic anhydride, urea, ammonium molybdate, and ferric chloride anhydride are added to nitrobenzene, stirred, and heated to reflux to obtain a precipitate. The obtained precipitate is hydrolyzed by adding an alkali, and then acidified by adding an acid. Cobalt phthalocyanine octacarboxylic acid is a similar method using pyromellitic anhydride instead of trimellitic anhydride, which is a raw material of iron phthalocyanine tetracarboxylic acid, and ferric chloride instead of ferric chloride anhydride. Can be manufactured.

  The metal phthalocyanine derivative is preferably supported on or mixed with an organic or inorganic carrier to form an allergen decomposing agent. A fiber is particularly preferred as the organic carrier. Since the fiber is bulky and has a large surface area, the metal phthalocyanine or its derivative efficiently contacts the allergen in the air.

  Examples of fiber materials include cellulosic fibers (cotton, hemp, rayon, etc.), protein fibers (wool, silk, etc.), polyamide fibers, polyester fibers, polyacrylic fibers, poval fibers, polyvinyl chloride fibers, Any natural fiber such as polyvinylidene chloride fiber, polyolefin fiber and polyurethane fiber, regenerated fiber, semi-synthetic fiber and synthetic fiber are used. Among these, cellulosic fibers, particularly cotton, have good water absorption, and therefore have favorable conditions for expressing an enzyme-like function as a water-absorbing medium.

  A fiber material carrying an allergen decomposing agent containing the metal phthalocyanine derivative as an active ingredient is placed in the living environment to decompose the protein-derived allergen.

  The fiber carrying the allergen degrading agent decomposes the allergen while isolating the human body with allergic constitution as clothing and futon from the allergen, and breaks down allergen entering from the outside as a curtain, as wallpaper and carpet It breaks down allergens that are floating or falling, and breaks down allergens that pass as an air filter.

The anti-allergen feather has the above-described metal phthalocyanine derivative supported on the feather. In the metal phthalocyanine derivative represented by the formula (II) used for this, R ¹ , R ² , R ³ and R ⁴ are SO ³ H groups, and n1, n2, n3 and n4 are 1 is preferable. Similarly, in the formula, it is preferable that M is Co or Fe.

  In the anti-allergen feather, the metal phthalocyanine derivative is preferably a sodium salt or a copper (II) salt of the compound represented by the formula (II).

  In the anti-allergen feather, the amount of the metal phthalocyanine derivative supported is preferably 0.1% by mass or more and 10% by mass or less based on the weight of the feather.

  The anti-allergen feathers, compositions and feather products containing the anti-allergen feathers are not treated with an anti-mite agent, and adsorb allergens derived from mites such as mite carcasses and excrement. Has an effect. Therefore, it is possible to remove mite-derived allergens.

  Hereinafter, the allergen decomposing agent and the decomposing method will be described in more detail with reference to Example 1.

Example 1
In order to confirm the effectiveness of the allergen-degrading agent, the efficacy of iron phthalocyanine tetracarboxylic acid as a metal phthalocyanine derivative was confirmed by test tube experiments, animal experiments, and safety by other experiments.

(Confirmation of drug efficacy)
The mite antigen DerfII (manufactured by Asahi Breweries) was selected as the allergen, and the electrophoresis when the mite allergen was mixed with iron phthalocyanine tetracarboxylic acid was compared with the electrophoresis of the allergen alone.

1. Preparation of solution Including each aqueous solution of iron phthalocyanine tetracarboxylate (Fe-Pc-COOK) and DerfII at a predetermined concentration (w / v%) in each experimental preparation example and IPG (Immobilized pH Gradient) buffer A mixed solution with a stock solution for swelling (Urea 8 mol / L, CHAPS 2 w / v%, IPG Buffer 2%, Bromophenol blue appropriate amount, distilled water) was prepared, and the test solutions of Experimental Preparation Examples 1 to 4 in Table 4 did.

  On the other hand, a mixed solution of a DerfII solution and a stock solution for swelling containing an IPG buffer was prepared and used as test solutions of Comparative Preparation Examples 1 to 4 in Table 4.

2. One-dimensional electrophoresis Prepare two types of gel films for single-dimensional electrophoresis (hereinafter referred to as “Stripe”), Strip pH 4-7 and Strip pH 3-10.5, and immerse each test solution in an appropriate amount of silicone oil to prevent drying. Added and left to stand for 10 hours. Each Strip was taken out from the test solution, washed with water, set in a one-dimensional electrophoresis apparatus, silicone oil for preventing drying was added, and one-dimensional electrophoresis was performed for 16 hours.

  The one-dimensional electrophoresis program for Strip pH 4-7 is shown in Table 1.

  The one-dimensional electrophoresis program for Strip pH 3 to 10.5 is shown in Table 2.

3. Two-dimensional electrophoresis (the operation is the same even if the strip of one-dimensional electrophoresis is different)
The Strip after one-dimensional electrophoresis was removed from the electrophoresis apparatus and washed with water. SDS (sodium dodecyl sulfate) buffer for equilibration (1.5 mol / L pH 8.8 Tris-Cl 50 mmol / L, Urea 6 mol / L, 87 v / v% Glycerol 30 v / v%, SDS 2 v / v% Stripo was immersed in 10 mL of a solution of DTT (dithiothreitol: dithiothreitol) 100 mg / 10 mL in Bromophenol blue (appropriate amount, distilled water) and allowed to permeate for 10 minutes. The Strip was taken out and immersed in 10 mL of a solution obtained by adding iodoacetamide (250 mg / 10 mL) to the SDS equilibration buffer and allowed to permeate for 10 minutes. The strip was taken out, washed with water and wiped off, and then attached to a two-dimensional electrophoresis apparatus in which a two-dimensional electrophoresis gel, filter paper, electrode gel, and molecular weight marker were set, and subjected to electrophoresis for 1 hour and 40 minutes.

  The two-dimensional electrophoresis program is shown in Table 3.

4). For preparation of staining and photographing materials, Silver Staining Kit, Protein manufactured by Amersham Biosciences was used.

The two-dimensional electrophoresis gel was immersed in a fixing solution (ethanol 100 mL, acetic acid 25 mL, distilled water up to 250 mL) and allowed to permeate for 30 minutes. A two-dimensional electrophoresis gel is immersed in a sensitizing solution (ethanol 75 mL, 25 w / v% glutaraldehyde 1.25 mL, 5 w / v% sodium thiosulfate 10 mL, sodium acetate 17 g, and made up to 250 mL with distilled water) for 30 minutes. Infiltrated. The washing in which the two-dimensional electrophoresis gel was immersed in 250 mL of distilled water and permeated for 5 minutes was repeated three times. The two-dimensional electrophoresis gel was immersed in a silver reaction solution (2.5 w / v% silver acetate solution 25 mL, 37 w / v% formaldehyde 0.1 mL, diluted to 250 mL with distilled water) and allowed to permeate for 20 minutes. The washing in which the two-dimensional electrophoresis gel was immersed in 250 mL of distilled water and permeated for 30 minutes was repeated twice. The two-dimensional electrophoresis gel was immersed in a developing solution (6.25 g of sodium carbonate, 0.05 mL of 37 w / v% formaldehyde, made up to 250 mL with distilled water) and allowed to permeate for 2 to 5 minutes. The two-dimensional electrophoresis gel was immersed in a stopping solution (3.65 g of EDTA-Na ₂ .2H ₂ O, made up to 250 mL with distilled water) and allowed to permeate for 10 minutes. The washing in which the two-dimensional electrophoresis gel was immersed in 250 mL of distilled water and permeated for 5 minutes was repeated three times.

  The silver-stained two-dimensional electrophoresis gel was photographed with an ATTO Printgraph-1 electrophoresis photographing apparatus.

  Along with the concentration of aqueous iron phthalocyanine tetracarboxylate solution in each experimental preparation, Strip pH for one-dimensional electrophoresis, gel gradient for two-dimensional electrophoresis (concentration of polyacrylamide contained in the gel), and two-dimensional electrophotography taken Table 4 shows the numbers of the figures on which the photographs of the electrophoresis gel are posted.

  In the photographs of FIGS. 1, 2, 3, and 4, the center spot row is a molecular weight marker, which is a measure of molecular weight. The spots of molecular weight markers in the photographs of FIGS. 1, 2, and 3 have molecular weights of 14.4, 20.1, 30, 45, 66, and 97 KDa (Kiro Dalton) in order from the bottom. The spots of molecular weight markers in the photograph of FIG. 4 are molecular weights of 3.5, 6.5, 14.3, 20.1, 30, 45 KDa in order from the bottom. Each horizontal axis of A and B divided by the center spot row of each photograph is the Strip pH of one-dimensional electrophoresis.

  The spot in A of each photograph is a mixture of potassium iron phthalocyanine tetracarboxylate and mite allergen, and the spot in B is mite allergen only. If there is no change in mite allergen due to potassium iron phthalocyanine tetracarboxylate, the spots in A and B will be the same, but from A, the spots around pH 5-6 disappear in A, and mite allergen due to potassium iron phthalocyanine tetracarboxylate. It can be seen that changes.

(Confirmation of safety)
In order to demonstrate that the allergen degrading agent can be used safely, the following experiment was conducted on iron phthalocyanine tetracarboxylic acid.

1. Skin primary irritation test for rabbits A knit fabric containing 1% by weight of iron phthalocyanine tetracarboxylic acid was used as a sample of functional fibers for allergen degradation.

  Six cases of 17-week-old Japanese white male rabbits (Kb1: JW (SPF)) having healthy and intact skin on the day before administration were selected, their backs were removed, and four administration categories (1 category: 2. 5 × 2.5 cm). Two of them were normal skin, and the other two were shaved lightly with a shaver and then stripped with cellophane tape to give damaged skin. A functional fiber moistened with water for injection was applied to each of normal skin and damaged skin, covered with gauze, and fixed with taping tape. The other was treated as an untreated site, and gauze and taping tape were applied in the same manner. Further, the covering was fixed using a cloth cover and a tube-type net bandage. After 24 hours, the functional fiber, gauze and taping tape were removed, and the administration site was wiped with slightly warm water.

  Macroscopic determinations were made before administration and at 1, 24, 48 and 72 hours after removal of the test substance. Judgment was carried out for erythema (scab formation) and floating species, respectively, according to Draize's criteria (Appendix 3). The average value and the standard deviation were calculated for erythema (scab formation), floating species, and their total score (TS) at each observation time point, divided into normal skin and damaged skin. In addition, according to the evaluation standard (Appendix 3) of ISO 10993-10, the average value of the primary irritation index (the erythema (scab formation) and the total score of floating species was evaluated for normal skin and damaged skin at 24, 48 and 72 hours, respectively , PII) was calculated, and the irritation intensity of the test substance was determined from the obtained primary stimulation index.

  As a result, at the functional fiber administration site, no irritant reaction was observed in the normal skin and the damaged skin throughout the entire observation period. The PII of the functional fiber is 0.0 for both normal skin and damaged skin, and the strength to irritation is determined as “Negligible”, and it is considered that there is no problem in the safety of the functional fiber to the skin.

2. Cumulative skin irritation test for rabbits The same allergen-degrading functional fiber was used as a sample, and was also used as rabbit damaged skin. A functional fiber moistened with water for injection was applied to each of normal skin and damaged skin, covered with gauze, and fixed with taping tape. Each other one site was an untreated site, and gauze and taping tape were applied in the same manner. Further, the covering was fixed using a cloth cover and a tube-type net bandage. After 23 hours, the functional fiber, gauze and taping tape were removed, and the administration site was wiped with slightly warm water. The administration period was 21 days, and irritation was evaluated visually 1 hour after daily removal. Judgment was carried out for erythema (scab formation) and floating seeds, respectively, based on the criteria for Draize. The average value and the standard deviation were calculated for erythema (scab formation), floating species, and their total score (TS) for each observation time point, divided into normal skin and damaged skin. After completion of the administration period, the animals were exsanguinated under pentobarbital sodium anesthesia, and each administration site skin was fixed with 10% neutral buffered formalin solution, followed by HE staining and histopathological examination.

  As a result, at the functional fiber administration site, no irritant reaction was observed in the normal skin and the damaged skin throughout the entire observation period. There was no change in histopathological examination. From the above results, it is considered that there is no problem in the safety of the functional fiber to the skin.

3. Ocular mucosal irritation test for rabbits Two groups, a non-washing group and a washing group, consisting of three 10-week-old Japanese white male rabbits each were set. Rabbits were confirmed to be free from changes in body weight and general condition after 7 days of preliminary breeding. In addition, on the day before administration, both eyes were not visually abnormal, and were subjected to fluorescein staining (fluor test paper, lot number 3990849, Weiss Eye Laboratories, USA), and slit lamp (SL-5, Kowa Co., Ltd.) Was used for the test after confirming that the cornea was not damaged.

  In each rabbit's right conjunctival sac, 100 mg of iron phthalocyanine tetracarboxylic acid powder, which was a test substance, passed once through a 300 μm mesh was placed, and the upper and lower eyelids were gently aligned and held for about 1 second. In the washing group, 30 seconds after administration, the inside of the conjunctival sac was washed with 230 to 330 mL of lukewarm water to remove the test substance. The left eye was left untreated in both the unwashed group and the washed group. At 1, 24, 48 and 72 hours after administration, the cornea, iris and conjunctiva were observed in comparison with untreated control eyes. In the non-washing group, an irritant reaction was observed even 72 hours after administration, so the observation period was extended to the 21st day. The observed findings were determined according to the evaluation criteria of Draize (Appendix 3), and the irritation was evaluated according to the classification method of Kay and Calandra (Appendix 4).

  In the non-washing group, clear irritant responses were observed in all cases, and corneal turbidity and surface roughening, iris congestion, conjunctival redness, floating seeds, secretions, etc. were observed. In addition, the cornea and iris were colored (green) by the test substance. These responses were most intense at 24 hours after administration. Thereafter, it gradually recovered, and the reaction of the cornea and iris disappeared by 72 hours after the administration and the reaction of the conjunctiva disappeared by the 10th day. In addition, only the coloring of the iris was recognized continuously until the 21st day after administration. Evaluation of ocular mucosal irritation was moderately irritating.

In the washing group, light redness was observed in the conjunctiva in all cases 1 hour after administration, but all disappeared 24 hours after administration. There were no changes in the cornea and iris. Evaluation of ocular mucosal irritation was Practically nonirritation. Iron phthalocyanine tetracarboxylic acid has a moderately irritating (M ₃ ) irritating property to the eye mucosa of rabbits, but the irritating reaction produced is reversible and can be reduced to Practically nonirritating (P) by washing. confirmed.

4). Intravenous administration of the extract to rats 844 mg sodium chloride, 1200 mg potassium chloride, 146 mg calcium chloride, 52 mg magnesium chloride, 342 mg dipotassium phosphate, and physiological saline prepared with 1000 mL purified water were added with 0. 0 functional fiber as a test substance. After immersion at a rate of 2 g / l mL and extraction in an autoclave at 121 ± 2 ° C. for 1 hour, the mixture was cooled to 20-30 ° C., stored at room temperature, and used within 24 hours.

  20 mL / kg of physiological fiber extract of functional fibers (4 g / kg in terms of functional fiber used for extraction) was repeated for 28 weeks on 26 male and female 6-week-old Crj: CD (SD) IGS (SPF) rats. Toxicity when administered intravenously was examined. A physiological saline was administered to the control group. As a result, no death was observed.

  No changes suggestive of the effects of functional fiber saline extract administration were observed in general conditions, body weight changes, food consumption changes, pathological anatomical examination, and histopathological examination. In urinalysis, hematology, blood chemistry, and organ weight, there were some items that showed a significant difference in the functional fiber saline extract administration group compared to the control group. These are considered to be accidental changes that are unrelated to toxicity, because they are fluctuations within the range and are not accompanied by changes in other test items that suggest the difference.

  Based on the above, it is considered that the functional fiber physiological saline extract is extremely low in toxicity, and the toxicological non-toxic amount under the test conditions is 20 mL / kg for both sexes (in terms of the functional fiber used for extraction). 4 g / kg).

5. Single oral dose toxicity test of extract on rats Five weeks old Crj: CD (SD) IGS (SPF) rats and 26 male and female rats were quarantined for 1 week, and no abnormalities were observed. Provided. Based on the body weight measured before pre-breeding, each group was assigned by the layer continuous randomization method. Surplus animals that were not assigned to groups were grouped. The age at the time of administration was 6 weeks for both males and females, and the body weight was 178 to 197 g for males and 122 to 142 g for females.

  Sodium chloride 844 mg, potassium chloride 1200 mg, calcium chloride 146 mg, magnesium chloride 52 mg, dipotassium phosphate 342 mg, and artificial saliva prepared with purified water 1000 mL were soaked with functional fiber as a test substance at a rate of 0.2 g / l mL, Extraction was performed for 1 hour at 121 ± 2 ° C. in an autoclave. Thereafter, it was cooled to 20-30 ° C., stored at room temperature, and administered within 24 hours.

  The dosage was 50 mL of extract per kg body weight based on the body weight immediately before administration. 50 mL of the extract is equivalent to 10 g in terms of extracted fiber. The number of administrations was one. After fasting for 18 hours or more from the evening of the day before administration, gavage was administered between 9:00 and 13:30 using a disposable syringe and an oral sonde. The observation period was 14 days after administration.

  Observation was continued up to 5, 15, 30 minutes, 1, 2, 4 hours before and after administration. From the day after the administration, it was observed once a day. Body weights were measured at 9:00 to 12:00 on the first, third, seventh, and tenth days before and after administration. At the end of the observation period, the organs and tissues of the head and thoracoabdominal region of all cases were observed to confirm the presence or absence of abnormalities.

  As a result, no death was observed in males and females of the artificial saliva extract administration group and the control group. In the general state observation after administration, no abnormality was observed in the male and female of the artificial saliva extract administration group and the control group. Both males and females in the artificial saliva extract administration group steadily gained weight and showed almost the same transition as the control group. There were no pathological anatomical abnormalities in males and females in the artificial saliva extract administration group and the control group.

  From the above, the lethal dose was estimated to be 10 g / kg or more in terms of functional fiber.

6). Single oral dose toxicity test of drug substance solution for rats Five male and female Crj: CD (SD) IGS (SPF) rats were quarantined for 1 week, and no abnormalities were observed. It was used for. Based on the body weight measured immediately before quarantine breeding, each group was assigned by the layer continuous randomization method. Surplus animals that were not assigned to groups were removed from the study on the day of grouping, euthanized and disposed of. The age at the time of administration was 6 weeks for both males and females, and the body weight was 172 to 186 g for males and 130 to 151 g for females.

  Immediately before administration, a necessary amount of iron phthalocyanine tetracarboxylic acid as a test substance was weighed and dissolved in purified water adjusted to pH 10.2 with 1N sodium hydroxide. After dissolution, the pH was adjusted to 7.11 using 1N hydrochloric acid, and then the dosage was prepared by making up with purified water so that the final concentration of iron phthalocyanine tetracarboxylic acid was 100 mg / mL. In compliance with the Guidelines for Drug Toxicity Test, the maximum dose that can be administered technically was set to 2000 mg / kg, which is the upper limit for oral administration, as the administration dose of the test substance. In addition, a control group to which a control substance (Japanese Pharmacopoeia purified water) was administered was set, and the total number of test groups was 2. Each group was assigned 10 males and 10 females.

  The administration liquid volume was 20 mL / kg, and was calculated individually based on the body weight immediately before administration on the administration day. The number of administrations was one. After fasting for 18 hours or more from the evening immediately before the administration, it was forcibly administered orally using a disposable syringe (Terumo Corp.) and an oral sonde (Fuchigami Instrument Store, Disposable Oral Sonde) and observed for 14 days. The observation of general condition and life and death was continuously observed before administration and 5, 15, 30 minutes, 1, 2, 4 hours after administration. From the day after the administration, it was observed once a day. The body weight was measured at 9:00 to 12:00 before administration and on 1, 3, 7, 10, and 14 days after administration. At the end of the observation period, the organs and tissues of the head and thoracoabdominal region of all cases were observed to confirm the presence or absence of abnormalities.

  As a result, there was no death in males and females of the test substance administration group and the control group. In general state observation after administration, liquid green stool was observed in all sexes in the test substance administration group 2 hours after administration on the day of administration, and green stool was observed 1 to 3 days after administration. The test substance is a dark green powder, and the green color of stool reflects this unique color. No abnormalities were observed in males and females in the control group. Both males and females in the test substance-administered group gained weight steadily and showed almost the same transition as the control group. Liquid stool is considered to be a transient diarrhea symptom caused by a large dose of the test substance, and none of the findings suggests toxicity.

  When an approximate lethal dose was determined by counting from the mortality rate during the observation period, the approximate minimum lethal dose of iron phthalocyanine tetracarboxylic acid under the test conditions was estimated to be 2000 mg / kg or more.

7). Skin sensitization test on guinea pigs 5-week-old male Crj; Hartley guinea pigs were divided into a vehicle control group and a test substance sensitization group, and the skin sensitization of functional fibers was tested by the Maximization method. A 10-fold amount of methanol was added to the functional fiber chopped as a test substance, followed by extraction at room temperature, and then the methanol was distilled off to obtain an extract of 151.88 g to 5.482 g of functional fiber.

  In the vehicle control group, dimethyl sulfoxide as a vehicle control was sensitized intradermally at a concentration of 10%, followed by transdermal sensitization with dimethyl sulfoxide, and then 10%, 1% and 0.1% functional fiber methanol extracts. As well as dimethyl sulfoxide. As a result, no skin reaction was observed at any initiation site.

  In the test substance sensitized group, the functional fiber methanol extract was sensitized at a concentration of 10%, and then induced with 10%, 1% and 0.1% functional fiber methanol extract and vehicle control. As a result, a skin reaction was occasionally observed at the site where the 10% methanol extract was induced, and the average evaluation score and positive rate at the site of the induction were 0.7 and 10% at 24 hours after the induction, and 1.4 and 40% at 48 hours, respectively. there were. In the 1% functional fiber methanol extract-induced site, erythema with an evaluation score of 1 was scattered, but no positive cases were observed. No skin reaction was seen at the 0.1% functional fiber methanol extract and the vehicle control initiation site. From the positive rate at 48 hours after induction, the functional fiber methanol extract was evaluated to have moderate (Grade III) skin sensitization by induction at a concentration of 10%.

  In the positive control group, 2,4-dinitrochlorobenzene (DNCB) was sensitized at a concentration of 0.1% and then induced with 0.1% DNCB and acetone. As a result, a skin reaction was observed at the DNCB inducing site in all cases, the positive rate at 48 hours after the inducing was 100%, and DNCB was evaluated to have severe (Grade V) skin sensitization.

  Each sensitizer was administered intradermally in combination with an adjuvant, and after 7 days, each sensitizer was occluded for 48 hours for percutaneous sensitization. On the 21st day after intradermal administration, each inducing substance was occluded and applied to the skin for 24 hours, and the skin reaction was determined at 24 and 48 hours after removal. The criteria for skin reaction are 0 for erythema and scab, 0 for slight erythema, 2 for obvious erythema, 3 for moderate erythema and 4 for erythema. Regarding floating species, there are no floating species, slight floating species 1, moderate floating species 2, strong floating species 3.

  Based on the above, the functional fiber methanol extract was considered to have skin sensitization properties to guinea pigs, and the lowest concentration was considered to be 10%. Moreover, the intensity of sensitization at the induction of 10% concentration was rated as moderate (Grade III).

8). Skin photosensitization test for guinea pigs The functional fiber methanol extract used in the skin sensitization test of 7 was tested for skin photosensitization by the Adjuvant and Strip method using 5-week-old male Crj: Hartley guinea pigs. Did. The dosing substance 0.1 mL was openly applied to the back of the guinea pig from which the hair had been removed, and after about 30 minutes, ultraviolet rays of about 10.2 Joules / cm ² were irradiated. The same treatment was performed for 5 consecutive days and photosensitized. On the 17th day after the final sensitization, 0.1 mL of each administered substance was removed and applied symmetrically to the back skin, and the right half of the animal was covered with aluminum foil and irradiated with about 10.2 Joules / cm ² of ultraviolet light. And light evoked. Skin reaction was determined at 24 and 48 hours after photoinduction.

  The test substance photosensitization group was sensitized by dissolving a methanol extract of functional fibers in dimethyl sulfoxide at a concentration of 10%, and was induced at a concentration of 1%. As a result, although erythema with a rating of 1 was scattered, no positive cases were observed, and all cases were determined to be negative. The vehicle control group was sensitized and challenged with dimethyl sulfoxide. As a result, no skin reaction was observed at any of the initiation sites. For the positive control group, 6-methylcoumarin (6-MC) was sensitized at a concentration of 5% and induced at a concentration of 1%. As a result, erythema with a score of 2 to 4 was observed at the ultraviolet irradiation site of the 6-MC induction site, and all cases were determined to be positive.

  Based on the above, it was considered that the methanol extract of functional fibers does not have skin photosensitization to guinea pigs.

9. Phototoxicity test on guinea pigs The functional fiber methanol extract used in the skin sensitization test of No. 7 was subjected to a phototoxicity test on male 5-week-old Crj: Htley guinea pigs by the method of Morikawa et al. For the test substance administration group, methanol extract of functional fiber dissolved in dimethyl sulfoxide at a concentration of 10%, dimethyl sulfoxide for the medium control group, and 0.05% 8-methoxypsoralen for the positive control group, respectively. As a substance, 0.03 mL of each administered substance was applied to the back of the guinea pig from which hair was removed. Thirty minutes after the open coating, ultraviolet rays of about 11.2 Joules / cm ² were irradiated. Skin reaction was determined 24 and 48 hours after irradiation.

  As a result, in the test substance administration group and the vehicle control group, no skin reaction was observed at any of the ultraviolet irradiation site and the non-irradiation site, and all cases were determined to be negative. On the other hand, in the positive control group, a skin reaction with a rating of 4 was observed at the ultraviolet irradiation sites in all cases.

  From the above, it was considered that the functional fiber methanol extract has no phototoxicity to guinea pigs.

10. Bacterial mutagenesis test Using Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli Escherichia coli WP2 uvrA, the presence or absence of mutagenic ability of functional fiber methanol extract was searched. The methanol extract is a residue obtained by adding 10 times the amount of methanol to the minced functional fiber, stirring and extracting at room temperature for 24 hours, and distilling off the methanol with a rotary evaporator.

  As a result, the number of revertant colonies by this test substance treatment does not increase more than twice as much as the negative control in both base pair substitution type and frameshift type strains regardless of the presence or absence of metabolic activation. Also, no dose response was observed. Therefore, it is determined that the methanol extract of functional fibers is not mutagenic under the test conditions.

11. Chromosome aberration test using mammalian cells The presence or absence of chromosomal aberration in functional methanol extract was searched. The test was conducted using DMSO as a medium. The maximum test dose of the test substance in the cell growth inhibition test was 5.0 mg / mL. As a result of the cell growth inhibition test, the 50% cell growth inhibition concentration was 5.0 mg / mL or more in the absence of a short-term metabolic activation system (hereinafter abbreviated as -S9mix method). In the presence of a short-term treatment metabolic activation system (hereinafter abbreviated as + S9mix method), it was 0.840 mg / mL. Precipitation of the test substance was observed at 0.313 mg / mL or more. Therefore, the test dose for the chromosomal aberration test was set to 3 doses diluted at a common ratio of 2, with the highest test dose of the -S9mix method being 0.313 mg / mL. In addition, the maximum test dose of the + S9mix method was set to 1.25 mg / mL, and four doses diluted with a common ratio of 2 were set.

  As a result of the short-time treatment method, the frequency of appearance of cells having chromosomal structural abnormality and ploidy cells in the -S9mix method was 5% or less at any test dose. However, in the + S9mix method, the frequency of appearance of cells having chromosomal structural abnormalities was 0.313 mg / mL or more, showing a dose-dependent increase and became positive. As a result of the short-time treatment method, the continuous treatment method was not performed because it was determined to be positive.

  In the positive control group in each treatment method, the frequency of appearance of cells having chromosomal structural abnormalities showed an appropriate value, and thus the test was judged to have been performed appropriately. From the above results, it was determined that the test substance has a chromosomal aberration inducing effect on Chinese hamster lung-derived fibroblasts (CHL / IU cells).

The cell growth inhibition test is as follows. Short-time treatment method 1; -S9mix method was performed by seeding 2 × 10 ⁴ cells (culture solution 5.0 mL) per one 60 mm diameter plastic petri dish and culturing for 3 days. The maximum test dose of the test substance was 5.0 mg / mL, and a total of 10 doses (0.010, 0.020, 0.039, 0.078, 0.156,. 313, 0.625, 1.25, 2.5 and 5.0 mg / mL). A vehicle (DMSO) control group was provided as a negative control. 50 μL of the medium or the test solution for each test dose was added to one petri dish per dose and allowed to act at 37 ° C. for 6 hours. After the action, the petri dish culture medium was removed, the cells were washed with physiological saline, and 5 mL of a new culture medium was added. Furthermore, the culture was continued for 18 hours. After culturing, the culture solution of the petri dish was removed, the cell surface was washed with physiological saline, and then fixed with a 10% formalin solution. After fixation, it was stained with 0.1% crystal violet solution. The cell growth rate was measured from the density of cell staining using a monolayer culture cell densitometer (Monocerator, Olympus Optical Co., Ltd.). At this time, the value of the medium control cell was 100%. From this, the 50% cell growth inhibitory concentration (approximate value) of the test substance was determined.

  Short-time treatment method 2; + S9mix method was the same as −S9mix method in which cells were seeded and cultured for 3 days. The number of petri dishes per dose and the dose of the test substance were the same as in the -S9mix method. 0.83 mL of the culture solution was removed from the petri dish, and 0.83 mL of S9mix was added to obtain an S9mix dilution (final concentration of S9: 5%). 50 μL of the medium or the test solution for each test dose was added to the petri dish and allowed to act at 37 ° C. for 6 hours. The operation after the action was the same as in the -S9mix method.

The chromosomal aberration test is as follows. The test dose of the test substance was determined by performing a cell growth inhibition test. As a result of the cell growth inhibition test, the 50% cell growth inhibition concentration was 5.0 mg / mL or more by the short-time treatment-S9mix method. Moreover, it became 0.840 mg / mL in the short-time treatment + S9mix method.
Precipitation of the test substance was observed at 0.313 mg / mL or more.

  From the above results, the test dose of the short-time treatment method in the chromosome aberration test was as follows. -S9mix method: 0.078, 0.156 and 0.313 mg / mL (ratio 2, 3 used). + S9mix method: 0.156, 0.313, 0.625 and 1.25 mg / mL (ratio 2, 2 used). As a result of the cell growth inhibition test, the maximum test dose of the test substance was 0.313 mg / mL, and a total of 3 doses diluted from the maximum test dose with a common ratio of 2 were set. Untreated and vehicle control groups were provided as negative controls, and mitomycin C (0.05 μg / mL) treated groups were provided as positive controls.

  At that time, colcemid (GIBCO / Lot No. 1125546) was added to the chromosomal specimen petri dish at a final concentration of 0.2 μg / mL two hours before preparation of the specimen in order to stop cell division at the middle stage of division. After 2 hours, the culture solution of each petri dish was transferred to a Spitz tube. Immediately, 2 mL of a 0.25% trypsin solution was added to each petri dish, and the cells were detached and then collected in the aforementioned Spitz tube and centrifuged (1000 rpm, 5 minutes). Discard the supernatant, add 5 mL of 0.075 M potassium chloride solution, and after hypotonic treatment for 15 minutes in a constant temperature water bath at 37 ° C., then add 0.5 mL of cooling fixative (mixed chilled methanol and acetic acid in 3: 1) And then semi-fixed, immediately centrifuged (1000 rpm, 5 minutes), and 5 mL of a new fixative solution was added. The same operation was repeated three times to completely fix the cells. The fixed cells were prepared in a cell suspension that was lightly turbid, dropped on a slide glass, air-dried, and stained with 1.7% Giemsa solution for about 15 minutes. Further, the cell proliferation rate petri dish was fixed and stained in the same manner as in the cell proliferation inhibition test described above, and the cell proliferation rate was measured.

  Under a microscope, 200 well-expanded metaphase images per treatment group (100 per petri dish) were observed, and the types of structural abnormalities and the number of cells with abnormalities were recorded. At the same time, the number of ploidy cells was recorded (37 or more chromosomes including 3 media were recorded as ploidy). In addition, in order to perform objective observation, it observed by the blind method.

  The types of chromosomal abnormalities were classified as follows. However, the gap means that the non-stained part is on the vertical axis of the dyed part, the width is equal to or less than the width of the dyed part, and the shape of the non-stained part is clear. If it is on the axis, its width is greater than the width of the chromatid and the shape of the unstained part is clear, or there is a fragment that is shifted from the axis of the chromosome or chromatid, exchange means chromosome or staining It was defined as mutual exchange by cutting two or more parts of the body, and other structural abnormalities were defined as others.

Abnormal structure Chromosome cut (ctb)
Chromosome exchange (four radial exchanges, cte)
Chromosome type break (csb)
Chromosome exchange (denocentric, circular, cse)
Others (fragmentation, frg)
Other chromosomal abnormalities Gap (g)
Numerical anomaly polyploid, endoruplication

As a result of the short-time treatment, the frequency of appearance of cells having chromosomal structural abnormalities and ploidy cells in the -S9mix method was 5% or less at any test dose. However, with the + S9mix method, the frequency of occurrence of polyploid cells of the chromosome was 5% or less at any test dose, but the frequency of appearance of cells with chromosomal structural abnormalities was 0.313, 0.625 and 1. There was a dose-dependent increase at 15.5, 49.5 and 73.0% at 25 mg / mL, respectively. Precipitation of the test substance was observed at 0.313 mg / mL or more. In the short-time treatment method -S9mix method positive control group (MMC), the appearance frequency of cells having chromosomal structural abnormality was 16.0%. In addition, in the + S9mix method positive control group (DMN), the frequency of appearance of cells having chromosomal structural abnormalities was 37.5%. Therefore, it was judged that the test was appropriately performed. As a result of the short-time treatment, it was determined to be positive, so the continuous treatment method was not performed. Test dose of the test substance to induce structural abnormalities 20% _{(D 20} value) was 0.35 mg / mL at + S9mix method.

12 Cytotoxicity test 8 g of functional fiber as a test substance was sterilized under high pressure steam (121 ° C., 20 minutes). After cooling and drying, 80 mL of the medium was added and the bottle was lightly plugged. After confirming that the test substance was sufficiently immersed in the medium, the sample was allowed to stand in a carbon dioxide incubator and incubated for 24 hours. Only the medium was taken out from the glass bottle, and this medium was used as a 100% test substance extract. The medium was diluted to 100, 80, 70, 50, 30 and 10%. The concentration of the test substance extract was set to 6 concentrations within an appropriate range in which the IC ₅₀ value can be calculated from the results of the preliminary study.

  About 2 × 15 mm functional fiber standard material and blank fiber negative material were each placed in a glass bottle and autoclaved. After cooling and drying, the medium was added at a rate of 10 mL to 1 g of the standard material or negative material, and lightly plugged. After leaving still in a carbon dioxide incubator and incubating for 24 hours, only the medium was taken out from the glass bottle, and this medium was used as a 100% standard material extract and a 100% negative material extract, respectively. Using the medium, standard material A was diluted to 8.0, 3.0, 1.0, 0.5 and 0.1%, and standard material B was diluted to 90, 80, 70, 50 and 30%. For the negative material, the 100% extract was used as it was.

  In an Eagle MEM medium (containing balanced salts of Eagle, 0.292 g / L L-glutamine, Invitrogen, Lot No. 1101728), 0.11 g / L sodium pyruvate (Wako Pure Chemical Industries, Ltd., Lot No. LDE0019) ), 2.2 g / L sodium hydrogen carbonate (Kanto Chemical Co., Ltd., Lot No. 106G1268), 0.1 mmol / L MEM non-essential amino acid (Invitrogen, Lot No. 1133557), 50 U / mL penicillin (Ashiyu Pharmaceutical Co., Ltd.) Co., Ltd., Lot No. 7QB03P) and 50 μg / mL streptomycin (Meiji Seika Co., Ltd., Lot No. SSD468) were added to obtain fetal bovine serum (FBS, Invitrogen, Lot No. A0282282) -free M05 medium. . Mv medium was prepared by adding 5 v / v% FBS to MBS medium without FBS.

Cell culture was performed using a carbon dioxide incubator at a temperature of 37.0 ± 1.0 ° C. (actual temperature: 36.9 to 37.4 ° C.) and a CO ₂ concentration of 5.0 ± 0.5% (actual concentration: 4.8-5.1%) and static culture under humidified conditions. The subculture was performed in a state where the cell density was about 30 to 70% of the flask bottom area. The medium in the flask was removed and rinsed lightly using Dulbecco's phosphate buffer without Ca ²⁺ and Mg ²⁺ . After removing PBS (-) by suction, a small amount of 0.05% trypsin and 0.02% EDTA · 2Na (Dojin Chemical Co., Ltd., Lot No. KC159) containing PBS (-) (trypsin / EDTA solution) was added and allowed to stand in a carbon dioxide incubator. After observing under a microscope and confirming that the cells were almost detached from the bottom of the flask, the medium was added to collect the cells, transferred to a centrifuge tube, and centrifuged at about 80 rpm for 2 minutes. The supernatant was removed and a new medium was added to loosen the cells to obtain a cell suspension. It diluted with the culture medium so that it might become the cell density of 1/3-1/10 before the subculture, and it seed | inoculated to the new flask.

  Cells are detached according to the passage method, and a cell suspension diluted with a medium so that the number of cells becomes 1000 cells / mL is added to a 6-well plate to which 3 mL of medium has been added in advance to 0.1 mL / mL. Each well was added and cultured for 24 hours in a carbon dioxide incubator. After removing the medium, 3 mL each of the test substance extract of each concentration, standard material A and standard material B, and negative material (100% extract only) was added. Four wells to which only the medium was added were provided as a control group. Four wells were used per concentration (n = 4). After each extract was added and cultured for 7 days in a carbon dioxide incubator, the medium in each well was removed and washed with 3 mL / well of PBS (−). After adding 3 mL of methanol to each well and allowing to stand for 10 minutes to fix the cells, methanol was removed, 3 mL of 5% Giemsa solution diluted with phosphate buffer (pH 6.4) was added, and allowed to stand for 10 minutes. Colonies were stained. Each well was washed once with purified water and then dried, and the number of colonies judged to be composed of 50 or more cells was counted with the naked eye or a real microscope.

After culturing V79 cells, a male Chinese hamster lung-derived established strain, at 100 cells / well (6 well plate) for 24 hours, each test substance (functional fiber) and each control substance (standard material A: 0.1% zinc dithiodicarbamate) (ZDEC) -containing polyurethane film, standard material B: 0.25% zinc dibutyldithiocarbamate (ZDBC) -containing polyurethane film and negative material: high-density polyethylene film) were added in an amount of 4 wells each and cultured for 7 days. The number of colonies formed was counted, and the concentration of the extract (IC ₅₀ value) was calculated when it was half the number of colonies when cultured in the same manner only in the medium (control group). The colony forming ability of the control group was 95%, indicating a good colony forming ability. There was no statistically significant difference in the number of colonies between the control group and 100% extract wells of negative material. The IC ₅₀ values of the standard material A and the standard material B were 1.32% and 68.92%, respectively, and both satisfied the acceptance criteria of the test.

Comparing the size of colonies in wells to which functional fiber extract was added and the control group, colonies tend to be smaller in the extract with a high concentration (70% or more), and there is a slight influence on the cell growth ability. It was suggested. However, the number of colonies forming the functional fiber extract was not different from that of the control group, and the IC ₅₀ value of the functional fiber extract was 100% or more, and no influence on the colony forming ability was observed.

  From the above results, it was determined that the inhibitory effect on the colony formation of the functional fiber extract was not observed under the present test conditions.

  Next, a preferred embodiment of the anti-allergen feather and a composition / feather product containing the same will be described.

  The present invention is an antiallergen feather on which a metal phthalocyanine compound represented by the formula (II) (hereinafter referred to as metal phthalocyanine compound (II)) or a salt thereof is supported as a derivative of the metal phthalocyanine. The amount of the metal phthalocyanine compound (II) or a salt thereof supported on the feathers is preferably 0.1% by mass or more and 10% by mass or less, more preferably 0.3% by mass or more with respect to the feather weight. It is 5 mass% or less, More preferably, it is 0.5 mass% or more and 3 mass% or less. This is because if the amount of the metal phthalocyanine compound (II) or a salt thereof is 0.1% by mass or more and 10% by mass or less, the effect of adsorbing allergens derived from anti-allergen feather mites is excellent.

  Examples of the material for the anti-allergen feathers include feathers collected from ducks, eagle birds, duck, mallards, Rouen duck, Chinese duck, Pekin duck, goose (Birgrim goose, Emden goose, etc.), and gray lagoon. Further, as the material for the anti-allergen feathers, feathers (large feathers, feathers having a wing part), downs (chests, fluffs), small feathers (small feathers), and the like can be used.

  Examples of the salt of the metal phthalocyanine compound (II) include a salt with an inorganic base and a salt with an organic base. Preferable examples of the salt with an inorganic base include alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt; and copper (II) salt and ammonium salt. . Preferable examples of the salt with an organic base include salts with trimethylamine, triethylamine, pyridine, picoline, ethanolamine, diethanolamine, triethanolamine, dicyclohexylamine and the like.

In the metal phthalocyanine compound (II) or a salt thereof, M is preferably Co or Fe in the formula (II). In the metal phthalocyanine compound or a salt thereof, in the formula (II), R ¹ , R ² , R ³ and R ⁴ are the same and are SO ₃ H groups, and n1, n2, n3 and n4 are the same 1 is more preferable. More specifically, such a metal phthalocyanine compound (II) or a salt thereof is represented by the following structural formula.

  The salt of the metal phthalocyanine compound (II) is more preferably a sodium salt or a copper (II) salt.

  The anti-allergen feather carrying the metal phthalocyanine compound (II) or a salt thereof can be produced, for example, by the following method. First, the feathers are pretreated. Pretreatment includes pre-dust removal to remove dirt and other impurities in raw material feathers, dust that cannot be removed by washing with pebbles, sand, fatty acids, etc., pre-wash dust removal to remove feather stains, water (room temperature water, hot water) Etc.).

  Next, the pretreated feathers are immersed in an aqueous solution of the metal phthalocyanine compound (II) or a salt thereof at 80 ° C. or higher and 100 ° C. or lower for 30 minutes to 2 hours, washed with water, dehydrated, and dried. Thus, an antiallergen feather carrying the metal phthalocyanine compound (II) or a salt thereof can be produced.

  The content of the metal phthalocyanine compound (II) or a salt thereof in the aqueous solution is preferably 0.01% by mass or more and 10% by mass or less, and 0.1% by mass or more and 5% by mass or less with respect to the feather weight. More preferred.

  The aqueous solution of the metal phthalocyanine compound (II) or a salt thereof may contain an acid generally used in an acid dyeing method such as formic acid, acetic acid, hydrochloric acid, phosphoric acid and citric acid. The acid is used in order to facilitate cationization of the amino group of the amino acid constituting the feathers and to reduce the solubility of the metal phthalocyanine compound so as to be easily carried on the feathers.

The anti-allergen feathers carrying the metal phthalocyanine compound (II) or a salt thereof may be further treated with a mordant, a fixing agent or the like. Examples of the mordant include tannic acid, aluminum salt (for example, aluminum acetate, raw alum, baked alum), chromic acid (for example, chromium acetate, chromium alum), iron salt (for example, ferric sulfamate, wood acetic acid). Iron, ferrous chloride, ferrous sulfate, etc.), tin salts (eg, sodium stannate, stannous chloride, etc.), copper salts (eg, copper acetate, etc.), barium salts (eg, barium chloride, etc.), etc. Can be used. As the fixing agent, a copper salt (for example, copper sulfate), an aluminum salt, a quaternary ammonium salt, or the like can be used. When treated with the mordant, the free SO ₃ H group or COOH group in the metal phthalocyanine compound (II) can form a salt, and this metal phthalocyanine compound (II) or salt is firmly supported on the feathers. be able to. Accordingly, even when the anti-allergen feathers carrying the metal phthalocyanine compound (II) or a salt thereof are washed, the carrying can be maintained for a long time.

  The present invention is a composition comprising anti-allergen feathers carrying a metal phthalocyanine compound (II) or a salt thereof. The composition may be processed into a molded product such as a feather product in combination with other materials.

  The present invention is a feather product including an anti-allergen feather carrying a metal phthalocyanine compound (II) or a salt thereof. Examples of the feather product include bedding such as a duvet and clothing such as a feather jacket.

  Hereinafter, the anti-allergen feathers will be described more specifically by Examples 2 and 3. In this example, the bulkiness was measured in a test room at a temperature of 20 ° C. and a relative humidity of 65% according to the JIS L 1903 feather test method.

(Example 2)
A goose feather (85% by mass down, 15% by mass small feather) (bulkyness 153 mm) subjected to a pre-dust removal treatment, a dust removal treatment before washing and a washing treatment with water was prepared.

  On the other hand, 0.5 mass% (weight ratio of feathers) of sodium cobalt phthalocyanine polysulfonate represented by the formula (IX) and 2 mass% of formic acid (weight ratio of feathers) were dissolved in 30 times the volume of water, A solution was prepared.

The feathers were immersed in this reagent solution and left at 97 ° C. for 50 minutes.
Most of the cobalt phthalocyanine polysulfonate was exhausted to the feathers.

  Thereafter, the feathers were thoroughly washed with water to remove the remaining reagent solution. Subsequently, dehydration and drying were performed to obtain antiallergen feathers (bulkyness 153 mm) carrying sodium cobalt phthalocyanine polysulfonate. The feathers thus obtained had no change in touch and bulkiness compared to feathers before the metal phthalocyanine compound or its salt was supported.

(Example 3)
Goose feathers (down 85% by mass, small feather 15% by mass) subjected to the pre-dust removal treatment, the dust removal treatment before washing and the water washing treatment were prepared.

  On the other hand, 0.5% by mass (sodium weight ratio) of cobalt phthalocyanine polysulfonate represented by the above formula (IX) and 2% by mass of formic acid (ratio of feather weight) are dissolved in 30 times the volume of water, A solution was prepared. The feathers were immersed in this reagent solution and left at 97 ° C. for 50 minutes. Thereafter, the feathers were thoroughly washed with water to remove the remaining reagent solution. Subsequently, it was dehydrated and dried.

  In addition, 1% by mass of copper sulfate pentahydrate (weight ratio to feathers) was dissolved in 30 times the volume of water to prepare a reagent solution. The feathers were immersed in this reagent solution and left at 30 ° C. for 30 minutes. As a result, copper ions were bonded to cobalt phthalocyanine polysulfonic acid to form an insoluble material which is a copper salt represented by the formula (X).

  Thereafter, the feathers were thoroughly washed with water to remove the remaining reagent solution. Subsequently, dehydration and drying were performed to obtain anti-allergen feathers carrying a copper salt (X) of a metal phthalocyanine compound. The feathers thus obtained had no change in touch and bulkiness compared to feathers before the metal phthalocyanine compound or its salt was supported.

(Evaluation)
1. Mite allergen adsorption test The mite allergen adsorption was measured as follows using the anti-allergen feathers carrying the metal phthalocyanine compound (II) or a salt thereof obtained in Examples 2 and 3. As a control sample, feathers that were not treated with the reagent solution in Examples 2 and 3, that is, goose feathers that had been subjected to the pre-dust removal treatment, the dust removal treatment before washing, and the washing treatment with water (down 85 mass%, small feather 15% by mass) was used.

  Each sample (2 mg) was put in a mite allergen antigen solution (Asahi Breweries, purified mite allergen rDer2 (trade name)) (1 μg / mL) (200 μl) and immersed at 25 ° C. for 1 hour. After the sample was taken out, the solution was centrifuged (10000 rpm, 3 minutes), and the supernatant (100 μl) was measured by ELISA.

Measurement method by enzyme immunoassay (ELISA) (1) Antigen coating 100 μl / well of the supernatant was injected into a microplate (96-well vinyl chloride plate, Dynatech) and maintained at 25 ° C. for 2 hours. did. Thereafter, the supernatant was removed from the well using a micropipette. The wells were washed 3 times with PBS solution.

(2) Blocking with BSA A BSA solution (VECTORUM BUMIN (trade name) (1% (w / v)) (1% (w / v)) was injected into the microplate at 100 μl / well and maintained at 25 ° C. for 1 hour. Thereafter, the supernatant was removed from the well using a micropipette. The wells were washed once with 0.05% Tween-PBS solution.

(3) Reaction of primary antibody to antigen A mite allergen antibody solution (manufactured by Asahi Breweries, anti-Derf2 monoclonal antibody (trade name)) (5 μg / mL) (5 μg / mL) was injected into the microplate at 25 ° C. Maintained for 2 hours.

(4) Reaction of enzyme-labeled secondary antibody Biotin-labeled anti-mouse IgG (H + L) antibody solution (VECTOR, BIOTINYLATED ANTI-MOUSE IgG (H + L) (trade name)) (1 μg / mL) Was injected into the microplate at 100 μl / well and maintained at 25 ° C. for 2 hours. Thereafter, the antibody solution was removed from the well using a micropipette. The wells were washed once with 0.05% Tween-PBS solution.

(5) Modification with avidin (AVIDIN) An avidin solution (manufactured by VECTOR, ALKALINE PHOSPHATASE AVIDIN D (trade name)) (100 units) was injected into the microplate at 100 μl / well and maintained at 25 ° C. for 0.5 hours. Thereafter, the supernatant was removed from the well using a micropipette. The wells were washed 3 times with 0.05% Tween-PBS solution.

(6) Reaction with Chromogenic Substrate A PNPP solution (P-NITROPHENYL PHOSPHATE (trade name) (500 μg / mL) manufactured by VECTOR, Inc.) (500 μg / mL) was injected into the microplate at 100 μl / well and maintained at 25 ° C. for 10 minutes. Then, 5N NaOH aqueous solution was inject | poured into 100 microliters / well, and reaction was stopped.

(7) Measurement Using a microplate reader (manufactured by BIO-RAD, MICROPLATE READER Model 550 (trade name)), absorbance at 405 nm or more was measured, and the concentration of mite allergen contained in each sample was quantified. From the mite allergen concentration before dipping the sample (1 μg / ml) and the mite allergen concentration after dipping the sample, the mite allergen adsorption rate of the sample was calculated according to the following formula.

Adsorption rate (%) = [(concentration of mite allergen after sample immersion: μg / ml) / (concentration of mite allergen before sample immersion: 1 μg / ml)] × 100

  As is apparent from the obtained results, it was confirmed that the anti-allergen feather carrying the metal phthalocyanine derivative was superior in ability to adsorb mite allergen without using an acaricide. Therefore, the feather of the present invention does not use an anti-mite agent and is excellent in anti-allergen effect.

  The allergen decomposing agent used in the present invention has been experimentally confirmed to have a medicinal effect of decomposing allergen by the action of a metal phthalocyanine derivative that is an active ingredient, and safety has also been experimentally confirmed. It can be used as a medicine.

  Furthermore, since the fiber material carrying the metal phthalocyanine derivative also has the effect of adsorbing allergens, it can be applied to fiber products containing it.

FIG. 1 is a photograph of a two-dimensional electrophoresis gel of test solutions of Experimental Preparation Example 1 and Comparative Preparation Example 1.

FIG. 2 is a photograph of two-dimensional electrophoresis gels of test solutions of Experimental Preparation Example 2 and Comparative Preparation Example 2.

FIG. 3 is a photograph of a two-dimensional electrophoresis gel of test solutions of Experimental Preparation Example 3 and Comparative Preparation Example 3.

FIG. 4 is a photograph of two-dimensional electrophoresis gels of test solutions of Experimental Preparation Example 4 and Comparative Preparation Example 4.

Claims (2)

Formula (I)

(In formula (I), M Fe, Co, Mn, Ti, V, Ni, Cu, Zn, Mo, W, a metal selected from Os) from ticks including derivatives of metal phthalocyanine represented by the active ingredient At least a part of an allergen-degrading fiber material made of cotton, yarn, woven fabric, non-woven fabric, knitted fabric, or paper containing natural fibers, synthetic fibers, semi-synthetic fibers or regenerated fibers carrying the allergen-degrading agent of , bedding, clothing, bedding, curtains, allergen content fibrillation維製products, characterized in that it has been shaped in the wallpaper or carpet,. The metal phthalocyanine derivative is represented by the following formula (II):

(In the formula (II), M is a metal selected from Fe, Co, Cu and Ni, R ¹ , R ² , R ³ and R ⁴ are the same or different COOH groups or SO ₃ H groups, and n1, n2 , allergen content fibrillation維製article according to claim 1, characterized in that the n3 and n4 compound represented by a positive number) that satisfies 1 ≦ n1 + n2 + n3 + n4 ≦ 8 0-4, or a salt thereof.

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