JP2004051534A - Anti-metal allergic agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain an anti-metal allergic agent which is effectively preventing and treating allergic diseases by metals such as nickel, cobalt, chromium, mercury, gold, etc., so-called metal allergy. <P>SOLUTION: The anti-metal allergic agent contains glutathione as an active ingredient. A unit dose is normally 1-1,000mg expressed in terms of glutathione. The anti-metal allergic agent is administered once to four times daily. <P>COPYRIGHT: (C)2004,JPO

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a useful antimetal allergic agent containing glutathione.
[0002]
[Prior art]
Metal allergy was first reported by Fleischmann in 1928, but in recent years, various metals have been present in the surrounding environment and have been increasing. Among them, metal allergies such as accessories, watches, and glasses worn on a daily basis are typical, but in addition to that, dental metals, tableware-derived metals, or foods rich in metals (soybean, tea, buckwheat, etc.) Metal allergies due to ingestion have been reported. Nickel, chromium, cobalt, mercury, gold and the like are known as the main metal allergens of these allergies.
Metal allergy is not caused by contact with solid metal, but ionized metal becomes a hapten, and after percutaneous invasion, it binds to the self protein (carrier) in the epidermis and sensitizes as a complete antibody. Therefore, measures such as conversion to other metals without using metals that cause allergic symptoms, and covering metal parts that come into contact with the skin with carbon films, synthetic resins, non-electrolyte substances, etc. have been taken. ing.
[0003]
On the other hand, with regard to the treatment and treatment of metal allergic diseases, active vitamin D ₃ , antibiotics, UV therapy, etc. are known, represented by steroidal drugs, but these symptomatic treatments temporarily relieve symptoms However, it is difficult to cure metal allergies.
[0004]
Glutathione is widely present in animals and plants and microorganisms. In humans, glutathione is not only used as a drug for the treatment of drug addiction and chronic liver disease, but also has various immunostimulatory or antioxidant effects. It is said to have a physiological activity.
However, it has been reported that glutathione derivatives such as S-dicarboxyethyl glutathione and its esters, glutathione thiol derivatives and the like have an antiallergic action (for example, JP-T-2-5000084, JP-A-3-48626). No. 10-204098, etc.), there is no report that glutathione has an anti-allergic action, while JP-A-3-48626 describes that glutathione has no anti-allergic action. Yes.
[0005]
[Problems to be solved by the invention]
An object of the present invention is to provide an antimetal allergic agent useful for prevention and treatment of metal allergy.
[0006]
[Means for Solving the Problems]
As a result of intensive studies to solve such problems, the present inventors have constructed a metal allergy mouse model and found that glutathione can effectively suppress metal allergy using the model, and have completed the present invention. .
That is, the present invention provides an antimetal allergic agent containing glutathione as an active ingredient.
[0007]
Hereinafter, the present invention will be described in detail.
The metal allergy referred to in the present invention refers to an allergic disease caused by metal, and examples of the metal include mercury, nickel, cobalt, tin, palladium, chromium, copper, platinum, zinc, and gold.
[0008]
Glutathione, which is an active ingredient of the present invention, is a known peptide composed of three amino acids, glutamic acid, cysteine and glycine, and the glutathione used may be any of reduced glutathione, oxidized glutathione, and a mixture thereof. Used as glutathione-containing yeast extract as well as glutathione. The glutathione-containing yeast extract preferably contains 1 to 15% glutathione, and examples of yeast used in this include torula yeast, baker's yeast, and brewer's yeast.
[0009]
The effective amount for preventing or treating metal allergy depends on the usual factors such as the nature, severity and weight of the problem. However, the unit dose is usually 1-1000 mg as glutathione. Usually the unit dose is administered one or more times a day, more typically 1 to 4 times a day, and the total daily dose is, for example, 1 to 4000 mg, more typically 1 to 2000 mg for an adult weighing 70 kg, for example. The dose should be within the range.
[0010]
Glutathione is orally administered as it is together with a conventional pharmaceutical carrier or as a solution, but may be a composition administered by other routes such as injection.
Particularly suitable oral dosage forms are unit dosage forms such as tablets, capsules and solutions.
[0011]
As the carrier, a binder, a disintegrant, a surfactant, a lubricant, a fluidity promoter, a corrigent, a colorant, a fragrance and the like can be used in addition to the excipient.
Suitable carriers include, for example, lactose, dextrin, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, calcium silicate, microcrystalline cellulose, cellulose, polyvinyl pyrrolidone, carboxymethyl cellulose, magnesium stearate, lauryl Examples include sodium acid.
[0012]
【Example】
Hereinafter, the present invention will be described in detail with reference to examples.
Test Example 1 Examination of Sensitization Concentration Back coat of 5-week-old male ddy mouse was clipped with clippers, and 10%, 15%, 20% nickel sulfate petrolatum sample (control is petrolatum only) was shaved from the back the next day. This was applied to the part every other day for a total of 4 times, and the metal salt concentration of the petrolatum sample used for sensitization was examined (n = 8). The induction concentration was fixed at 0.4%.
As a result, a sufficient allergic reaction was not observed in 10%, and in 20%, some mice died of weight loss from the start of application, but some solids were observed. As shown in FIG. 1, an increase in swelling was observed in the non-sensitized group after 18 hours from the induction. In particular, since the difference between the sensitized group and the non-sensitized group was the largest at 48 hours, the evaluation was performed 48 hours after the induction.
The allergenicity was evaluated by measuring the foot-pad swelling with a peacock dial thick gauge gauge (manufactured by Ozaki Mfg. Co., Ltd.). Significance test was performed by Tukey's multiple comparison between groups.
[0013]
Test Example 2 Confirmation of Antigen Specificity In the same manner as in Test Example 1, mice sensitized with a 15% nickel sulfate petrolatum sample were treated with 0.4% nickel chloride saline sample solution or 0.2% chromium sulfate saline sample. The solution (control was physiological saline only) was administered and swelling was observed (n = 8).
As a result, as shown in FIG. 2, a significant delayed allergic reaction was observed in the nickel chloride sample solution, but no significant difference was obtained in the chromium sulfate sample solution (FIG. 3).
From these results, it was confirmed that this method was not influenced by anions and was a nickel antigen-specific reaction.
[0014]
Test Example 3 Examination of Induced Concentration Mice sensitized with a 15% nickel sulfate petrolatum sample in the same manner as in Test Example 1 were swollen 48 hours after induction with nickel sulfate in a concentration range of 5 ppm to 893 ppm (0.4%). The rate was measured (n = 4).
The results are shown in FIG.
As seen in FIG. 4, there was a tendency for swelling to increase in a concentration-dependent manner, and significant nickel allergy could be induced at 10 ppm or more.
[0015]
Example 1
The back coat of 5-week-old male ddy mice was clipped with clippers, and 0.2 g of 15% nickel sulfate petrolatum was applied every other day for one week from the next day (total 4 times). After sensitization, 20 μL of 0.4% nickel sulfate physiological saline sample solution was subcutaneously injected into a foot-pad to induce.
As for glutathione, 100 mg / 10 mL / kg (control is 10 ml / kg of ultrapure water) is orally administered 30 minutes before the induction, or 10 mg / 10 mL / kg (control is physiological saline) is intravenously administered 5 minutes before the induction. (N = 5).
The results are shown in FIG.
As is apparent from FIG. 5, it can be seen that glutathione exhibits a significant nickel allergy inhibitory effect in both oral administration and intravenous administration.
[0016]
【The invention's effect】
As described above, according to the present invention, an anti-metal allergic agent containing glutathione as an active ingredient and useful for the prevention and treatment of metal allergy is provided.
[Brief description of the drawings]
FIG. 1 is a graph showing the change over time in the swelling rate of induced swelling when sensitized with a 15% nickel sulfate petrolatum sample.
FIG. 2 is a graph showing the change over time in the swelling rate of the induced swelling when sensitized with a 15% nickel sulfate petrolatum sample and induced with a 0.4% nickel chloride physiological saline sample solution.
FIG. 3 is a graph showing changes over time in swelling rate when sensitized with a 15% nickel sulfate petrolatum sample and administered with 0.2% chromium sulfate.
FIG. 4 is a graph showing the swelling rate at 48 hours after sensitization with a 15% nickel sulfate petrolatum sample and induction with nickel sulfate in a concentration range of 5 to 893 ppm.
5 is a graph showing the inhibition rate by administration of glutathione in Example 1. FIG. In the figure, ** indicates that the risk rate is significant at 1%.

Claims (1)

An anti-metal allergic agent characterized by containing glutathione as an active ingredient.

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