WO2015040067A1

WO2015040067A1 - Preparation and use thereof in atopic dermatitis

Info

Publication number: WO2015040067A1
Application number: PCT/EP2014/069814
Authority: WO
Inventors: Gisela Rauch-Petz
Original assignee: Pg Naturpharma Gmbh
Priority date: 2013-09-17
Filing date: 2014-09-17
Publication date: 2015-03-26
Also published as: DE202013008190U1

Abstract

The invention relates to a composition for the supportive treatment of atopic dermatitis, containing borrage oil, carob seed oil and/or evening primrose oil and Omega 3 fatty acids-rich in concentrations such that the ratio of γ-linolenic acid to eicosapentaenoic acid is 1.33 1 to 1.66: 1.

Description

Preparation and its use in atopic dermatitis

The present invention relates to a composition containing fish oil, borage oil and / or evening primrose oil, vitamin D and vitamin E.

The composition on which the invention is based is used, for example, as a supplementary balanced diet for skin diseases such as psoriasis or atopic dermatitis, which is also known as atopic dermatitis or atopic dermatitis.

background

For years, the diseases of the atopic form of the population increase. Even in infants and toddlers, the diseases can be diagnosed. They cause minor impairments in quality of life, including serious illnesses of those affected, including hospitalization, mental health and work loss.

Among the atopic diseases are in addition to asthma and allergic rhinitis in particular, the allergic reactions of the skin, namely the atopic dermatitis (atopic dermatitis, atopic dermatitis) to call. For atopic dermatitis there is no generally accepted therapy recommendation. Rather, being in medical

Treatment usually developed an individualized treatment plan. So far, various drug therapies with cortisone, antihistamines and leukotriene antagonists are combined with consistent skin care, plant ointments, thalassotherapy, brine baths, but also autogenic training. In the case of dietary measures, the recommendations for avoiding ingestion outweigh the known allergens.

Balanced diets are "dietary foods for special medical purposes." They were included as a new product category in Section 1 (4a) of the German Diet Ordinance (DiätV) in 2001. They are subdivided into fully balanced diets (No.1) and supplemented balanced diets (No. 2) and include compositions that are specially processed or formulated. Balanced diets are being developed for the dietary treatment of individuals who derive a specific medical indication

have nutritional needs due to nutritional medicine. This central

Purpose is in the definition of balanced diets of § 1 Abs. 4a DiätV under the term "dietary treatment" of a disease, disorder or

Complaint summarized. These include, for example, complete formula diets with a nutrient standard formulation as a tube feed or certain supplementary foods for the treatment of liver cell or kidney failure as well as phenylanlaninfreie protein replacement preparations to meet the protein needs of children with phenylketonuria.

The use of this dietary food must be for the patient

especially beneficial and effective. This means that a complementary balanced diet can only be justified if a "special diet" is used

This nutritional need must not be achieved by modifying the normal diet, using other foods for a particular diet, or a combination of both at a reasonable cost, for example, a condition that is susceptible to nutrition, such as for example, in diabetics.

The supplemented balanced diets are intended to partially nourish patients with impaired, disabled or disturbed ability to ingest, digest, absorb, metabolize or excrete some common

Food or certain nutrients contained therein or their metabolites, or the diet of patients with any other medically related

Nutritional needs. Supplementary balanced diets, in contrast to fully balanced diets, are not intended for the exclusive nutrition of patients. Rather, they must be consumed in addition to the normal diet to complete the

To meet the nutritional needs of the patient. Thus, they are compositions with a standard nutrient formulation or with a condition specific for or specific to a particular disease or disorder

Nutrient formulations that are not suitable for use as the only food source.

Due to the nutritional purpose, supplementary balanced diets are not

Drug. While medicinal products are used to cure or alleviate disease, balanced diets have the sole purpose of nutritionally supporting and optimizing the treatment of diseases.

In addition, supplemented balanced diets are considered to be in their own right

Composition significantly different from the foods of daily consumption

to distinguish their dietetic character.

State of the art

In WO 2010/067206 A1, the treatment of atopic dermatitis and itchy skin symptoms in domestic animals by means of a mixture of hemp, linseed and rapeseed oil is described. Here the ratio of linoleic acid to a-linolenic acid should be at least 2: 1 and the ratio of γ-linolenic acid to

Stearidonic be at least 2: 1.

Omega-3 and omega-6 acids such as linoleic, linolenic and

Eicosapentaenoic acid is combined with other substances in GB 2 453 157 A1 to provide a composition for the treatment of skin diseases, i.a. to treat atopic dermatitis and eczema. Here the composition is applied purely externally.

EP 1 634 599 A1 and EP 1 781 307 B1 protect a nutritional supplement or pharmaceutical composition containing a fat component, a protein component and a carbohydrate component and include whey and casein. This dietary supplement or pharmaceutical composition has a weight ratio of casein to whey of 1: 1 to 1: 2.4 and the

Composition contains:

a) at least 3 grams of arginine per 100 grams of protein;

b) at least 10% by weight of linoleic acid based on the total fatty acids;

c) at least 1% by weight of alpha-linolenic acid based on the total fatty acids; d) at least one long-chain polyunsaturated fatty acid in an amount of more than 0.1 wt.% Based on the total fatty acids, the long-chain polyunsaturated fatty acid selected from the group consisting of

Docosahexaenoic acid, arachidonic acid and eicosapentaenoic acid;

e) 5 to 25% by weight of at least one polyunsaturated fatty acid based on the total fatty acids; And

f) 2 to 12 g of indigestible oligosaccharides having a degree of polymerization of 2 to 100 per 100 grams dry weight of the composition.

The "double heart system eyes plus eyesight + protection" capsules contain in a 1st capsule 15 mg lutein, 1 mg zeaxanthin, 0.4 mg vitamin A, 2 mg vitamin B6, 1, 0 pg vitamin B12, 10 mg zinc, 40 pg selenium, 60 mg vitamin C, 4 mg vitamin E, 640 mg sea fish oil with 140 mg DHA and in a second capsule 725 mg sea fish oil with 160 mg docosahexaenoic acid, 68 mg borage oil with 15 mg gamma-linolenic acid, 5 pg vitamin D, 2 mg of vitamin B2, 13.6 mg of vitamin E. These capsules are called

Dietary supplements are distributed and should contribute to eye health.

Various studies are concerned with omega-3 fatty acids and omega-6 fatty acids and their different effects on the human body, such as e.g. Evangelos C. Rizos, MD, PhD; Evangelia E. Ntzani, MD, PhD; Eftychia Bika, MD; Michael S. Kostapanos, MD; Moses S. Elisaf, MD, PhD, FASA, FRSH

(September 2012), "Association Between Omega-3 Fatty Acid Supplementation and Risk of Major Cardiovascular Disease Events: A Systematic Review and Meta- analysis." JAMA 308 (10): 1024-1033,

Bent, Stephen; Bertoglio, Kiah; Hendren, Robert L. (March 2009), "Omega-3 Fatty Acids for Autistic Spectrum Disorder: A Systematic Review", J Autism Dev Disord 39 (8): 1 145-54,

Van De Rest, O .; Geleijnse, JM; Kok, FJ; Van Staveren, WA; Dullemeijer, C; Olderikkert, MGM; Beekman, ATF; De Groot, CPGM (August 2008), "Effects "Fatty acids from fish: the anti-inflammatory potential of longevity.", Neurology 71 (6): 430-38, Wall R, Ross RP, Fitzgerald GF, Stanton C (2010). chain omega-3 fatty acids ", Nutr Rev 68 (5): 280-9, Ruggiero C, Lattanzio F, Lauretani F, Gasperini B, Andres-Lacueva C, Cherubini A (2009)," Omega-3 polyunsaturated fatty acids and immune-mediated diseases:

inflammatory bowel disease and rheumatoid arthritis ", Curr Pharm Des15 (36): 4135-48,

Belch JJ, Hill A (2000), "Evening primrose oil and borage oil in rheumatologic conditions". At the. J. Clin. Nutr. 71 (1 Suppl): 352S-6S,

Fan, Yang-Yi and Robert S. Chapkin (9 September 998). Journal of Nutrition 128 (9): 141 1-4, Horrobin, David (January 1, 2000), "Essential fatty acid metabolism and its

modification in atopic eczema ", American Journal of Clinical Nutrition 71 (1): 367S- 72S,

Williams, Hywel C (13 Dec 2003). "Editorial: Evening primrose oil for atopic dermatitis - Time to say goodnight". BMJ 327 (7428): 1358-9.

None of these proposed compositions or studies come to satisfactory results regarding the treatment or support of atopic dermatitis.

task

It is therefore the object of the present invention to provide a composition which can be used as a food, dietary supplement and especially as a supplemental balanced diet in atopic dermatitis. Here, especially herbal ingredients should be present.

description

This object is achieved by a composition for the supportive treatment of atopic dermatitis containing borage oil, St. John's wort oil and / or evening primrose oil and omega-3 acid rich fish oil in concentrations, so the ratio of γ-linolenic acid to eicosapentaenoic acid is from 1.33: 1 to 1.66: 1.

Surprisingly, the Applicant has found that it is precisely in this ratio, the ingredients of borage oil, St. John's Wort oil and / or evening primrose oil and omega-3 acid-rich fish oil are particularly effective in skin diseases of the atopic Formenkreises.

The borage oil advantageous for the invention has a content of from 18 to 25% by weight, preferably from 17 to 18% by weight, of γ-linolenic acid.

Furthermore, in a preferred embodiment, the composition according to the invention contains the oil of fatty fish, which is generally rich in omega-3 fatty acids. These omega-3 fatty acids may be included in the composition in the form of triglycerides, but there may also be ethyl esters of said fatty acids. These ethyl esters are partially synthetic substances obtained from fish oil by work-up.

Omega-3 fatty acids are in part essential for the human organism. Above all, the predominantly herbal α-linolenic acid (ALA) is an essential nutrient, since it can not be formed by the body. α-linolenic acid will turn into the formation of the omega-3 fatty acids docosahexaenoic acid (DHA) and

Eicosapentaenoic acid (EPA) is needed. α-linolenic acid is present in vegetable oils such as linseed oil (56-71%), hemp oil (28%), walnut oil (about 15%), rapeseed oil (5-16%) and soybean oil (4-1 1), also low in animal fats contain. However, the fish oils described here mainly contain eicosapentaenoic acid and docosahexaenoic acid as omega-3 fatty acids.

The most suitable fish oil is a purified and / or winterized and / or deodorized fat oil derived from family Engraulidae (anchovies), Carangidae (spiny mackerels), Clupeidae (herring), Osmeridae (stinte),

Salmonidae (salmonidae), Scombridae (mackerel and tuna) and

Ammodytidae (sand eels) is obtained. Winterization is carried out to prevent clouding of the oil at low temperatures (e.g., in the refrigerator)

Avoid, usually by contaminants such as waxes, mucilage or higher melting triglycerides is caused. For this purpose, the oil is cooled to a low temperature, for example 5 - 10 ° C. In this

Temperature range develops during a "maturity period" lasting up to 24 hours (crystallization)

Precipitation and filtration are these crystals removed. The composition of the oil does not change by the separation of these solid constituents, since only impurities are removed. The winterization makes it cold-resistant and stays clear even at refrigerator temperature.

Preferably, the omega-3-rich fish oil is a content

Elcosapentaensäure from 25 to 55 wt .-% to. For the sake of clarity, the concentration of elcosapentaenoic acid as the free fatty acid is calculated for this concentration indication, even if the oil of elcosapentaenoic acid is present as triglyceride or ethyl ester. Fish oils with a content of elcosapentaenoic acid, calculated as free fatty acid, of 38 to 51% by weight are particularly suitable for the present invention.

Suitable for the present invention, for example, the fish oils from Epax AS, selected from EPAX 6000 TG / N, EPAX 6000 TG, EPAX 6000 EE, EPAX 4510 TG, EPAX 6500 EE, EPAX 5500 EE, EPAX 4020 TG, EPAX 4020 EE, EPAX 6015 TG and EPAX 6015 EE.

Particularly suitable are EPAX 6015 TG and EPAX 4020 TG. Also preferred are EPAX 4510 TG, EPAX 4020 EE and EPAX 6015 EE.

The composition according to the invention is mixed from said oils, the omega-3-acid-rich fish oil and the γ-linolenic acid-rich borage, Johanniskern and / or evening primrose oil such that the ratio of gamma-linolenic acid to elcosapentaenoic acid of 1, 33 : 1 to 1, 66: 1.

For filling in single or multiple doses, depending on the content of

oils used so the composition in unit doses, e.g.

Soft gelatin capsules, packaged or dosed in a multidose dosing with measuring cups, measuring spoons or the like so that an adult with the number of prescribed single doses or single doses per day 250-450 mg of elecosapentaenoic acid from omega-3 acid-rich fish oil and 450 to 600 mg γ-linolenic acid from borage oil, evening primrose oil and / or Johanniskernöl takes.

For children, this distribution of the daily dose can easily achieve a reduced dosage by reducing the number of prescribed single doses or single doses of a multi-dose dosage form according to body weight.

Thus, for example, a composition can be provided which

- 250 - 450 mg of eicosapentaenoic acid from omega-3 acid-rich fish oil

- 450 - 600 mg γ-linolenic acid from borage oil

- 900 - 1,700 I.E. Vitamin D

- 50 - 90 mg vitamin E,

This amount corresponds to the dosage per day in adults.

To facilitate intake, the daily dosage may be divided up to 12 individual doses. These single doses may be, for example, soft gelatin capsules. The composition can also be packaged as a liquid in a bottle and provided with a measuring cup or measuring spoon for dosing. Also conceivable would be a dosage form in drinking ampoules. The Weichgeiatinekapseln can be given due to the lamination of the taste here certainly the preference.

Furthermore, it is advantageous if in addition vitamin D and vitamin E are contained in the composition. Vitamin D is in a concentration of 800 to 2,000 I.E. Based on the daily dosage for an adult advantageous.

In particular, a concentration equivalent to a daily dosage of 1,000 to 1,600 I.U. is appropriate. Vitamin E can be calculated in concentrations of 40 to 100 mg, preferably from 60 to 80 mg to the daily dosage of one

Be adult.

The composition according to the invention is used in particular for the supportive treatment of atopic dermatitis, atopic dermatitis or psoriasis.

Examples Example 1: Soft Gelatin Capsule Glandol ATOP

The following ingredients are filled into a transparent soft gelatin capsule size 11 minims, so that the final weight of the capsule is 875.5 mg:

Borage oil 450.30 mg

Fish oil concentrate EPAX 6015 TG 109,09 mg

RRR-alpha-tocopherol concentrate 25.76 mg

Cholecalciferol 0.35 mg

Example 2: Treatment cases

In an observational study, a total of 59 patients with atopic dermatitis aged 12 to 77 years (mean age 36 years) consumed 2 soft gelatine capsules of Glandol ATOP 3 times daily for a period of 12 weeks. At the end of the observation period, a significant

Reduction of the severity of the skin change noted. There was also a significant reduction in itching and a decrease in sleep disturbances. Participants were highly satisfied with the type of capsule consumed, the amount of intake and the taste and smell of the soft gelatin capsule Glandol ATOP.

Claims

claims

1. Composition for the supportive treatment of atopic

Dermatitis containing borage oil, styrofoam oil and / or evening primrose oil and omega-3 acid rich fish oil in concentrations such that the ratio of γ-linolenic acid to eicosapentaenoic acid is from 1.33: 1 to 1.66: 1.

2. A composition according to claim 1, wherein the borage oil has a content of 18 to 25% by weight, preferably from 17 to 18% by weight, of γ-linolenic acid.

3. The composition of claim 1 or 2, wherein the omega-3 acid rich fish oil is a purified, winterized and deodorized, fatty oil derived from fish of the families Engraulidae, Carangidae, Clupeidae,

Osmeridae, Salmonidae, Scombridae and Ammodytidae.

A composition according to any one of claims 1 to 3, wherein the omega-3 acid rich fish oil has a content of eicosapentaenoic acid of from 25 to 55% by weight, preferably from 38 to 51% by weight.

Composition according to any one of claims 1 to 4, wherein the omega-3 acid rich fish oil is selected from EPAX 6000 TG, EPAX 6000 EE, EPAX 4510 TG, EPAX 4020 TG, EPAX 4020 EE, EPAX 6015 TG, EPAX 6015 EE ,

6. The composition according to any one of claims 1 to 4, wherein additionally

Vitamin D and Vitamin E are included.

7. The composition according to any one of claims 1 to 5, comprising

- 250 - 450 mg of eicosapentaenoic acid from omega-3 acid-rich fish oil

- 450 - 600 mg γ-linolenic acid from borage oil

- 900 - 1,700 I.E. Vitamin D

- 50 - 90 mg vitamin E,

this amount corresponds to the dosage per day in adults and this amount may be divided into 1 to 12 units.

8. Use of the composition according to claim 1 to 7 for

supportive treatment of atopic dermatitis