WO2006000421A2

WO2006000421A2 - Ige antibody repressing agent comprising alpha cyclodextrin

Info

Publication number: WO2006000421A2
Application number: PCT/EP2005/006817
Authority: WO
Inventors: Keiji Terao; Daisuke Nakada
Original assignee: Wacker Chemie AG
Current assignee: Wacker Chemie AG
Priority date: 2004-06-24
Filing date: 2005-06-23
Publication date: 2006-01-05
Anticipated expiration: 2006-12-24
Also published as: WO2006000421A3; JP2006008568A

Abstract

The present invention provides a safe IgE antibody repressing agent and foodstuff of high therapeutical effect. This IgE antibody repressing agent and foodstuff efficient in improving IgE allergic diseases comprises alpha-cyclodextrin as an active component.

Description

IgE Antibody Repressing Agent and Foodstuff

The present invention relates to an IgE antibody repressing agent and foodstuff. More particularly, it relates to IgE antibody repressing agent and foodstuff having an effect of ameliorating allergic diseases characterised in comprising alpha-cyclodextrin.

These last 10 years there is a growing tendency all over the world in contraction and mortality of allergic diseases as a result of changes in eating habits and housing conditions . Nowadays, for the population in Japan, one out of three suffers from some allergic disease such as bronchial asthma, atopic dermatitis or allergic nasal inflammation.

It is well known that the origin of such diseases is that immunoglobulin (IgE) is produced in antigen-antibody reaction in the organism and, by stimulation of the cell membrane of mast cells, histamine, leucotriene, etc. is released. These released substances have such action as to promote the permeability of blood vessels, contract the smooth muscles, etc. and, for that reason, may induce such effects as the leakage of leucocytes and proteins from blood vessels or, through inflammation, the contraction of the bronchial tube leading to asthma. In order to alleviate an allergic condition, (e.g. chlorophenyl-amine, diphenhydramine, etc.) antihistamine agents (e.g. chromotin, tranirast, etc.) , mast cell membrane stabilisers or adrenocortical hormones are administered in a peroral way or in the form of a cream.

However, antihistamine agents exert side effects such as drowsiness or thirst and mast cell membrane stabilisers are not expected to produce an alleviating effect upon an already established disease. On the other hand, side effects of adreno-cortical hormones include gastrointestinal troubles, liver troubles, diabetes, high blood pressure, etc. Furthermore, all these substances are applied for a temporary treatment and after the suspension of their administration a relapse may cause various problems .

As a safe IgE antibody repressing agent with reduced side- effect, a purified glucomannan is used containing at least 90% edible fibre obtained from Amorphophallus konjak (devil's tongue) powder, which is made easily soluble in water by grinding treatment. Since this material is produced from Amorphophallus konjak, it can also be used as a food. However, the production of this IgE antibody repressing agent and food is quite laboursome, and it is therefore desirable to provide an IgE antibody repressing agent and foodstuff that are more easy to produce and safely consumable.

The problem to be solved in this invention is to provide an IgE antibody repressing agent or food having no side effect, and which are easy to produce and safely consumable.

This problem is solved by an IgE antibody repressing agent comprising alpha-cyclodextrin.

As a result of thorough investigations aiming at solving the above problems, the inventiors have discovered that alpha- cyclodextrin exhibits an IgE antibody repressing ability. Alpha-cyclodextrin is a hardly digestible dextrin having an effect to reduce blood sugar level and reduce the amount of neutral lipids. It is marketed as functional food additive. By the addition of alpha-cyclodextrin, the authors of this invention obtained an IgE antibody repressing agent and food having the effect of ameliorating an IgE allergic condition. Thus they attained to the above named invention, wich comprises the following preferred embodiments (1) to (3) : (1) An IgE antibody repressing agent comprising alpha- cyclodextrin, wherein the allergic disease is bronchial asthma, atopic dermatitis or allergic nasal inflammation. (2) An IgE antibody repressing foodstuff having an effect of improving allergic diseases characterised in comprising alpha- cyclodextrin. (3) An IgE antibody repressing foodstuff according to said (2) wherein the allergic disease is bronchial asthma, atopic dermatitis or allergic nasal inflammation.

The IgE antibody repressing agent and foodstuff of this invention is efficacious for allergic diseases such as bronchial asthma, atopic dermatitis or allergic nasal inflammation. Since this IgE antibody repressing agent and food comprises alpha-cyclodextrin as active component that has been recognised as a functional food additive, their use is of high safety permitting a general and wide range application.

Alpha-cyclodextrin contained in the active component of this invention can be produced from natural substances such as maize, potato, etc.; particularly suitable is the inexpensive maize. A commercially available α-cyclodextrin can also be used as α-cyclodextrin of this invention. The IgE antibody repressing agent of this invention can be used in the form of powder, granule, capsule, chewable, tablet, etc. In this case, generally applied additives can be admixed, such as starch, lactose, white sugar, mannitol, carboxymethyl cellulose, corn starch, inorganic salts, etc., in an appropriate formulation. Further, in case of necessity, other known additives can also be added directly such as, for instance, binders, disintegrators, surface active agents, flavouring agents, colorants, aroma, etc. The daily intake amount of this IgE antibody repressing agent or food for an adult is preverably more than 100 mg without upper limit, more preferably 1 g to 100 g, most preferably 5 g to 15 g, expressed in terms of α- cyclodextrin content as active component. The dose is preferably established in function of the health condition. The intake can be done any time but, whenever possible, intake is suggested orally before sleeping or at the time or during meals in the morning, at noon or in the evening.

An IgE antibody repressing foodstuff of this invention includes foods in liquid, gel, sol, solid etc., form containing α-cyclodextrin. Examples of a liquid foodstuff include mineral water, tea, sport drink, apple juice, orange juice, beer, wine, etc. beverages with dissolved α- cyclodextrin as an IgE antibody repressing drink. A gel-form food can be an α-cyclodextrin containing solid jelly, tofu, egg tofu, etc. A sol-form food can be an α-cyclodextrin containing liquid jelly or the like. A solid form food can be rice, hulled products etc. obtained with α-cyclodextrin addition and processed to foodstuff, e.g. udon, soba, baked soba, noodles, macaroni, various breads, cereales, milk products, etc.

The invention further relates to a process for the production of an antiinflammatory active agent, preferred an antiallergic active agent, especially preferred an IgE Antibody Repressing Agent charcterised in that α-cyclodextrin is incorporated into foodstuff .

The incorporation is preferably done by mixing, dissolving or blending.

The invention further relates to the use of α-cyclodextrin as antiinflammatory active agent, preferred as antiallergic active agent, especially preferred as IgE Antibody Repressing Agent. For this purpose it is applied in the doses named above.

The following examples show detailed embodiements of the invention.

Example 1 : Preparation of IgE antibody repressing agent The IgE antibody repressing agent was CAVAMAX^® W6 Food grade (commercially available from Wacker-Chemie GmbH, Munich) containing α-cyclodextrin produced from maize starch by enzymatic reaction. As a daily intake for an adult, this IgE antibody repressing agent was given in a daily dose of 5 to 15 g, directly or dissolved in water, etc., or mixed with rice etc. foods. Example 2: Preparation of IgE antibody repressing food (1) CAVAMAX^® W6 Food grade containing α-cyclodextrin produced from maize starch by enzymatic reaction was dissolved in mineral water, tee, sport drink, apple juice, orange juice, beer, wine etc. beverages in an amount of 5g/100 mL so as to obtain an IgE antibody repressing beverage. (2) Further, α-cyclodextrin was combined with white rice or whole grained rice in an amount of 5 g for 0.18 litres to prepare an IgE antibody repressing rice food. Moreover, using this IgE antibody repressing rice, rice ball, risotto, curry rice, etc. foodstuffs were prepared. (3) Further, udon, vermicelli, soba, Chinese vermicelli, baked soba, macaroni, jelly sticks, bifun, etc. IgE antibody repressing products were prepared containing 6 g α-cyclo¬ dextrin for 100 g product. By incorporating α-cyclodextrin, no change was observed in the taste of these drinks and foods.

Example 3 : Test of antiinflamatory activity (1) Experimental method 5 g IgE antibody repressing agent produced in Example 1 was dissolved in 100 mL water and given to patients with bronchial asthma, atopic dermatitis or allergic nasal inflammation, daily, before meals, during a period of two months and the change in their health state was observed.

(2) Results Out of four patients showing the condition of bronchial asthma, all patients showed improvement without using steroids, bronchodilators or the like that they have had used before the experiment and all have recovered. For two from among seven patients in condition of atopic dermatitis, symptoms such as erythroderma, dermatorrhagia, eczema, xeroderma, etc. have vanished to such extent that the skin portion involved could not be distinguished from the normal skin surface. In the case of four patients, this skin portion could be discriminated but the patient was almost without itching and the condition has improved. There was only one patient for which the effect was unclear. Further, out of 12 patients with allergic nasal inflammation, for seven patients, the symptoms caused by pollen during the spring in the previous year have completely vanished. For three patients the sneezing, nasal discharge, nasal congestion, etc. were alleviated. Unclear effect was experienced for two patients only. The effect of IgE antibody repressing agents against these allergic diseases is summa-rised in Table 1 according to the sex and age of the patients.

Example 4 : Test of antiinflamatory activity As example of asthma healing, the history of a 47 years old fully recovered patient was as follows. Infantile asthma started in childhood, then he began to play baseball in the middle school and his asthma temporarily stopped. Asthma relapsed at the age of 36 and, from that time, broke out once in a month and, for ten years, became increasingly violent with the age. During that time, steroids, antibiotics, peroral antiphlogistics/antipyretics were adminis-tered. The IgE antibody repressing agent of the Example 1 of this invention was applied as described in Example 3 for two months. Though alcohol consumption and smoking were also interrupted before the experiment, asthmatic symptoms have completely disappeared. Thereafter, application was interrupted for half a year but symptoms did not reappear.

Hence, it can be established that the IgE antibody repressing agent of this invention shows a high therapeutical effect for allergic diseases such as allergic nasal inflammation and the like. It can be expected that for patients with unclear effect a sustained application would bring amelioration or healing. Table 1: Results with IgE antibody repressing agent

O : Indicates the relevant section Bronchial asthma/recovery: disappeared symptoms; improve-ment frequency of persistent cough decreased; unclear effect: no change Atopic dermatitis/recovery: disappeared symptoms; improve¬ ment: less intense itching; unclear effect: no change Allergic nasal inflammation/recovery: disappeared symptoms; improvement: sneezing, nasal discharge, nasal congestion alleviated; unclear effect: no change.

The IgE antibody repressing agent and food of this invention is effective for allergic diseases such as bronchial asthma, atopic dermatitis and allergic nasal inflammation. These IgE antibody repressing agents and foodstuffs were found as safe functional foods and, since their active component is the inexpensive α-cyclodextrin available in great quantities, a highly economic and wide application has been made possible.

Claims

1. IgE antibody repressing agent having an effect of improving allergic diseases characterised in comprising alpha-cyclodextrin.

2. IgE antibody repressing agent according to Claim 1 wherein the allergic disease is bronchial asthma, atopic dermatitis or allergic nasal inflammation.

3. IgE antibody repressing foodstuff having an effect of improving allergic diseases characterised in comprising alpha-cyclodextrin.

4. IgE antibody repressing foodstuff according to Claim 3 wherein the allergic disease is bronchial asthma, atopic dermatitis or allergic nasal inflammation.

5. The IgE antibody repressing agent according to claim 1 or 2 characterised in that it is used in the form of powder, granule, capsule, chewable, or tablet.

6. The IgE antibody repressing agent according to claim 1, 2 or 5 characterised in that the intake is orally before sleeping or at the time or during meals in the morning, at noon or in the evening.

7. An IgE antibody repressing foodstuff according to claim 3 or 4 characterised in that the foodstuff is in liquid, gel, sol or solid form.

8. Process for the production of an antiinflammatory active agent, preferred an antiallergic active agent, especially preferred an IgE Antibody Repressing Agent charcterised in that α-cyclodextrin is incorporated into foodstuff.

9. Use of α-cyclodextrin as antiinflammatory acive agent, preferred as antiallergic active agent, especially preferred as IgE Antibody Repressing Agent.