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Meyan Kökü İran

Atopik Dermatitin meyan kökü jeliyle tedavisi

Glycyrrhiza glabra L. cilt için dermatit, egzama, kaşıntı ve kistler de dahil olmak üzere bitkisel ilaç olarak kullanılmıştır. Topikal preparat olarak Meyan ekstresinin etkisi atopik dermatitde değerlendirildi. Bitki toplandı ve uygun bir çözücü ile süzme ile ekstre edildi. Glycyrrhizinic asite dayanarak titrimetri yöntemi kullanarak öz standartlaşdırıldı. Farklı topikal jeller farklı solvent kullanılarak formüle edilmiştir. Topikal hazırlıklar ayarlandıktan sonra iki haftadan fazla zamanda en iyi formulasyonlar çift-kör klinik çalışma taban jeliyle karşılaştırılmada atopik dermatitde öğrenildi. Jelleştirici ajan nihai formülasyon içinde en iyi sonuçlar gösterdiği gibi Propilen glikol öz ve Carbopol 940 için en iyi çözücü oldu. Glycyrrhizinic asit miktarının özü % 20.3 ve terkiplerine içinde % 19.6 olarak tespit edilmiştir. Yüzde iki meyan topikal jel eritem, ödem ve iki haftadan çok olan kaşıntı skorlarının azaltılmasında % 1 ‘den daha etkili oldu. Sonuçlar meyan özünün atopik dermatitin tedavisinde etkili bir ajan olarak kabul edile bileceğini gösterdi.

 

Giriş

Atopik dermatit atopik durumun kutanöz ifadesidir, ailenin asıtım durumundan, bahar nezlesi veya hastaların %70 kadarında dermatitin olmasıyla karakterize olunuyor. Hanifin yaptığı incelemede atopik dermatit davasıyla ilgili dört akım hipotez özetlemiştir: devirli fonksiyonel nükleotit bozukluğu, süper antijen rolü, IG-E aracılı alerji ve gida alerjenleri ve antijene karşı otoimmun. Topikal kortikosteroid kremler veya merhemler atopik dermatit akut fişeklerini kontrol eden tedavinin temelidir, onların geniş immünomodülatör etkileri nedenine esasen. Bu ve diğer tedaviler yan etkilere sahip oldukları için yeni tedavi yöntemlerini değerlendirmek gereklidir. Özellikle çeşitli otlar, Glycyrrhiza uralensis (Çinli bir meyan türü) karışımından oluşan geleneksel Çin ilaçları yaygın atopik dermatiti olan çocuklar için bir tedavi seçeneği sağladı. Doğu Asya’da deri hastalığı için bir elyaf bitki olan Çin meyan kökü (G. uralensis), steroid benzeri maddeler içerir, dahili olarak ele alındığında, veya topikal olarak uygulandığında, hızlı bir şekilde yardım sağlıyor. Glycyrrhiza glabra L. Avrasyada yereldir ve Avrupa’da (örnek, İspanya, İtalya, Fransa), Orta Doğu (örnek Suriye, İran, Türkiye, Irak), ve Asya’da yetiştiriliyor. Kullanılan kısımlar sonbaharda toplanan kurutulmuş köklerdir. G. glabra önemli miktarda liquiritigen ve liquiritin ve glycyrrhetinic asit ve glycyrrhisin gibi triterpenoids olan flavonlar içeriyor. Liquiritigenin, disodyum glycyrrhetinic asitin glycyrrhisin antienflamatuar etkinliğe sahip olduğu gösterilmiştir. Glycyrrhiza glabranın önemli bir anti-enflamatuar ve anti-allerjik etkisi vardır. Glycyrrhizin antikor oluşumu, stres tepkisi, ve inflamasyon kortizol adlı inhibisyonu pekiştiriyor. G. glabranın alkol ekstresi Staphylococcus aureus, Streptococcus mutans, Mycobacterium smegmatis’in ve Candida albicansa karşı in vitro anti-mikrobiyal aktivite göstermiştir. Antimikrobik etki çoğunluğu soflavenoid bileşenlerden dolayıdır. Bu çalışma atopik dermatit olan hastalarda meyan jelinin klinik etkinliği (% 1 ve% 2) karşılaştırmak için tasarlanmıştır.

 

Gereç ve yöntem

Gereçler

Aşağıdaki kimyasallar tedarikçilerinden alındığı gibi kullanılmıştır. Metil ve propil paraben, propilen glikol, PEG 200, PEG 300, PEG 400, izopropil alkol, gliserin, trietanolamin, metanol, aseton, etanol, NaOH, NH3, formalin (Merck), Carbopol 940 (BF Goodrich).

 

Bitkinin materyalları

Glycyrrhiza glabra L. kökleri 2001 yılında, baharda, İran’ın güneyinde, Şirazdan toplanmıştır. Kurutulmuş kökler tüm materyallerin kafes boyutu 0.5mm-den büyük olmadan geçe bilmesi için pudralandı.

 

Ekstraksiyon prosedürü

Toz kökler (600 g) bir gün için 1 litre metanol içinde eritildi ve bu adım filtre kağıdı ile filtrasyon yoluyla ardından iki kez tekrarlandı. Süzülen madde düşürülen basınç altında kuruyana kadar buharlaştırıldı ve (122 g,% 20.33) tartıldı.

 

Glycyrrhizic asitin tayini

Meyan kökü (2 g), 1 saat asetonun içinde % 3 HNO3 20 ml ile karıştırıldı ve daha sonra süzüldü ve 10 ml aseton ile yıkandı. Tortu 20 ml aseton ile geri akıtıldı tekrar filtre edildi ve bu işlem üç kez tekrarlandı. Bir araya getirilen ekstreler 100 ml aseton ile seyreltildi ve 40 ml Etanolla yıkandı, %30 NH3-ün 0,9 ml-i karışıma damla-damla ilave edildi. Amonyum glycyrrhizate süzüldü, aseton (50 ml toplam) ile 2-3 kez yıkandı ve 25 ml su içinde çözülmüş, 20 ml formalin ilave edildi ve 1 dakika sonra, karışım, 0.1 N NaOH ile titre edildi. Bu yöntem aynı zamanda meyan kökü preparatlarda Glycyrrhizic asit belirlenmesi için kullanılmıştır. Deney üç kez tekrarlandı.

 

Formülasyonların hazırlanması

PEG 200, 300, 400, izopropil alkol ve propilen glikol kurutulmuş ekstresi için ortak çözücü olarak kullanılmıştır ve propilen glikol en iyi levigator olarak seçilmiştir. Tablo I incelenen preparatların bileşenleri gösteriyor. Carbopol 940 korunmuş su (% 0.18 metil paraben ve propil paraben% 0.02) ve gece boyunca gliserin içinde dağıtıldı. Ekstrakt, propilen glikol içinde çözülmüş ve polimer dispersiyonu ilave edildi ve 10 dakika için 500 rpm’de bir çift kanatlı karıştırıcı (IKA-Werk, Almanya) ile karıştırıldı, ve 10 dakika boyunca pH 6.4 ‘e trietanolamin ile nötralize edildi ve daha sonra 300 rpm’de 10 dakikaya kadar karıştırıldı. Formülasyonlar 4, 25, ve 40 ‡ C iki hafta değerlendirilmenin fiziksel kararlılığını sağlamak için bekletildi. Klinik deneme için final formülasyonlar USP XXIV dayalı mikrobiyolojik olarak kontrol edildi.

 

Klinik çalışma ve istatistiksel analiz

Çalışma çift kör, randomize (basit rastgele örnekleme), prospektif, plasebo-kontrollü bir denemedir. Klinik araştırmanın birincil sonlanım noktası şiddetli ödem, kaşıntı ve eritemdir. 0.5 birimlerinin genel bir ortalama farkı varsayımı üzerinde ve 0.5 birimlerinin standart sapması 78 hastadan bir güç elde edildi.

 

Sonuç

Nihayet biz atopik dermatit yönetimi konusunda güncel yaklaşımları özetlemek istiyoruz. Tedavinin nihai amacı, hastanın günlük hayatlarında daha fazla sosyal faaliyetler için bir fırsat vermekti. Cilt bakımı, kaşıntı kontrolü ve arttırıcı faktörler dışlanması kontrolü tedavinin üç yönüdür ve bu mükemmel bir tedavi aracı için hastanın yanıtı dikkate alan topikal meyan hazırlıkların uygun kullanımı vardır.

 

The treatment of atopic dermatitis with licorice gel

Introduction

Atopic dermatitis is the cutaneous expression of the atopic

state, characterized by a family history of asthma, hay

fever, or dermatitis in up to 70% of patients.1 Hanifin

summarized four current hypotheses concerning the cause

of atopic dermatitis in his review: cyclic nucleotide

dysfunction, the role of superantigen, Ig-Emediated allergy

to airborne and food allergens, and autoimmunity to selfantigen.

2 Topical corticosteroid creams or ointments are

themainstay of therapy to control the acute flares of atopic

dermatitis, probably due to their broad immunomodulatory

effects.3,4 As these and other therapies have side effects

it is necessary to evaluate new therapeutic methods. A

traditional Chinese medication consisting of a mixture of

several herbs, especially Glycyrrhiza uralensis (a Chinese

species of licorice) has provided a therapeutic option for

children with extensive atopic dermatitis.5,6 Chinese

licorice root (G. Uralensis) which is a staple herb for skin

disease in east Asia, contains steroid-like substances,

which, when taken internally, or even applied topically,

rapidly provide relief.7

Glycyrrhiza glabra L. is native to Eurasia and

cultivated in Europe (e.g. Spain, Italy, France), the

Middle East (e.g. Syria, Iran, Turkey, Iraq), and Asia.

Those parts used are the dried roots collected in the

autumn.8 G. glabra contains substantial amounts of

flavones, such as liquiritigenin and liquiritin, and

triterpenoids, such as glycyrrhetinic acid and glycyrrhizin.

Liquiritigenin, disodium glycyrrhetinic acid and

glycyrrhizin have been shown to have antiinflammatory

activity.9–11 Glycyrrhiza glabra has significant

anti-inflammatory and anti-allergic activity.

Glycyrrhizin reinforces cortisol’s inhibition of antibody

formation, stress reaction, and inflammation. Alcohol

extract of G. glabra has displayed anti-microbial activity

in vitro against Staphylococcus aureus, Streptococcus

mutans, Mycobacterium smegmatis, and Candida albicans.

The majority of the antimicrobial effects are due to

soflavenoid components, with the saponins having a

lesser antibacterial effect.12 This study was designed to

compare the clinical efficacy of licorice gel (1% and 2%)

with that of placebo, in patients with atopic dermatitis.

M Saeedi1, K Morteza-

Semnani2 and M-R Ghoreishi3

Departments of 1Pharmaceutics and

2Medicinal Chemistry, Faculty of

Pharmacy, Mazandaran University of

Medical Sciences, Sari, Iran;

3Dermatologist, Sari, Iran

Glycyrrhiza glabra L. has been

used in herbal medicine for skin

eruptions, including dermatitis,

eczema, pruritus and cysts. The

effect of licorice extract as topical

preparation was evaluated on

atopic dermatitis. The plant was

collected and extracted by percolation

with suitable solvent.

The extract was standardized,

based on Glycyrrhizinic acid by

using a titrimetry method.

Different topical gels were formulated

by using different cosolvents.

After standardizing of

topical preparations, the best

formulations (1% and 2%) were

studied in a double–blind clinical

trial in comparison with base gel

on atopic dermatitis over two

weeks (30 patients in each

group). Propylene glycol was

the best co-solvent for the

extract and Carbopol 940 as

gelling agent showed the best

results in final formulations. The

quantity of glycyrrhizinic acid

was determined 20.3% in the

extract and 19.6% in the topical

preparation. Two percent licorice

topical gel was more effective

than 1% in reducing the scores

for erythema, oedema and itching

over two weeks (p,0.05).

The results showed that licorice

extract could be considered as

an effective agent for treatment

of atopic dermatitis. (J Dermatol

Treat (2003) 14: 153–157)

Received 20 September 2002

Accepted 3 June 2003

Keywords: Atopic dermatitis — Glycyrrhiza glabra — Oedema —

Erythema — Itching

Correspondence:

M. Saeedi, Faculty of Pharmacy, Taleghani Blvd., P.O.Box: 48175-861,

Sari, Iran; Tel/Faxz151-3243109. E-mail: saeedi_m_2001@yahoo.co.uk

Journal of Dermatological Treatment (2003) 14, 153–157

# 2003 Journal of Dermatological Treatment. All rights reserved. ISSN 0954-6634 153

Materials and methods

Materials

The following chemicals were used as received from the

suppliers. Methyl and propyl paraben, propylene glycol,

PEG 200, PEG 300, PEG 400, isopropyl alcohol,

glycerin, triethanolamine, methanol, acetone, ethanol,

NaOH, NH3, formalin (Merck), Carbopol 940 (BF

Goodrich).

Plant material

Glycyrrhiza glabra L. roots were collected from Shiraz, in

the south of Iran, in spring 2001. The dried roots were

powdered so that all the material could be passed

through a mesh size no larger than 0.5 mm.

Extraction procedure

Powdered roots (600 g) were macerated in 1 l of

methanol for one day, and the step was repeated

twice, following by filtration through filter paper. The

filtrate was evaporated to dryness under reduced

pressure and weighed (122 g, 20.33%).

Glycyrrhizic acid determination

The licorice extract (2 g) was stirred with 20 ml of 3%

HNO3 in acetone for 1 hour, then filtered and washed

with 10 ml of acetone. The residue was refluxed with

20 ml of acetone, filtered again, and this operation

repeated three times. The combined acetone extracts

were diluted to 100 ml, and washed down with 40 ml of

ethanol; 0.9 ml of 30% NH3 was added dropwise to the

mixture. Ammonium glycyrrhizate was filtered, washed

2–3 time with acetone (50ml total), and dissolved in

25 ml of water; 20 ml of formalin was added and after

1 min the mixture was titrated with 0.1 N NaOH in the

presence of phenolphthalein as indicator.13 This method

was also used for determination of glycyrrhizic acid in

licorice preparations. The assay was repeated three

times.

Preparation of the formulations

PEG 200, 300, 400, isopropyl alcohol and propylene

glycol were used as co-solvent for dried extract and

propylene glycol was chosen as the best levigator.

Table I shows the constituents of the investigated

preparations. Carbopol 940 was dispersed in preserved

water (methyl paraben 0.18% and propyl paraben

0.02%) and glycerin overnight. The extract was

dissolved in propylene glycol and was added to the

polymer dispersion and stirred with a double bladed

mixer (Ika-werk, Germany) at 500 rpm for 10 min, and

neutralized by triethanolamine to pH 6.4 and then

mixed at 300 rpm for 10 min. The formulations were

stored at 4, 25, and 40C to ensure physical stability

evaluation for two weeks. Final formulations for the

clinical trial were controlled microbiologically based on

USP XXIV.

Clinical trial and statistical analysis

The study was a randomized (simple-random sampling),

double blind, prospective, placebo-controlled trial. The

primary endpoint of the clinical trial is severity in

oedema, itching and erythema. On the assumption of an

overall mean difference of 0.5 units and a standard

deviation of 0.5 units, 78 patients (26 in each group)

were required to achieve a power of 95% to reject a null

hypothesis of equality, applying a two-sided test at the

5% significance level. With an estimated fraction of 35%

of the patients being not evaluable, a total of 108

patients, aged over 15 years, with clinically diagnosed

mild to moderate degrees of atopic dermatitis (1.

pruritus and scratching, 2. course marked by exacerbation

and remissions, 3. lesions typical of eczematous

dermatitis, 4. personal or family history of atopy, 5.

clinical course lasting longer than 6 weeks) were

recruited.1 Before enrollment to the study, written

informed consent was obtained from all patients or

the parents of those under the age of 18 years. Patients

receiving systemic or topical steroids, antibiotics, or

Formulation* Composition % (w/w)

Licorice

extract

Carbopol Propylene

glycol

Glycerin

F1 1 0.30 10 5

F2 1 0.30 15 5

F3 1 0.30 20 5

F4 1 0.40 15 5

F5 1 0.40 20 5

F6 1 0.50 10 5

F7 1 0.50 15 5

F8 1 0.50 20 –

F9 1 0.50 20 5

F10 1 0.75 10 5

F11 1 0.75 15 5

F12 1 0.75 20 5

F13 1 1.00 10 5

F14 1 1.00 15 5

F15 1 1.00 20 5

F16 2 0.25 20 5

F17 2 0.50 20 5

F18 2 0.75 20 5

F19 2 1.00 20 5

Placebo – 0.50 20 5

*Each formulation consists of preserved water (propyl paraben

0.02%w/w and methyl paraben 0.18% w/w) to 100 g. The

formulations was neutralized by triethanolamine to pH=6.8.

Table I

Formulations composition

154 M Saeedi et al The treatment of atopic dermatitis

other effective topical therapy within the previous 7

days, pregnant women, nursing mothers, and patients

with other skin disorders were excluded. Lesions

location was classified as head and neck, trunk,

hands, and feet.

The topical preparations (1% and 2% licorice gels and

placebo) were administered to patients, in three groups,

three times a day for two weeks. The overall clinical

response was assessed by the investigator based on

effect on oedema, itching, erythema and scaling,

according to the following 4-point scale: absent=0,

mild=1, moderate=2, and severe=3. Follow up of

patients ceased after two weeks. ANOVA, followed by

Student-Newman-Keuls test, was used to determine

significant differences between groups and p,0.05 was

considered significant.14

Results and discussion

Licorice contains as its major active ingredient the

triterpene glycoside glycyrrhizin (also known as glycyrrhizic

or glycyrrhizinic acid) in concentrations ranging

from 1% to 24%, depending on sources and methods of

assay. Glycyrrhizin on hydrolysis yields glycyrrhetinic

(or glycyrrhetic) acid and two molecules of glucoronic

acid.8 Thus the standardization of licorice extract and its

preparations were performed by determination of glycyrrhizinic

acid. From the glycyrrhizic acid determination

conducted according to the previously described

method, the quantity of glycyrrhizic acid obtained was

20.3±0.81% and 19.6±0.74% in licorice extract and

licorice gel respectively. All investigated formulations in

the clinical trial used the criteria of USP microbial

limitation.

On observing the clinical features of atopic dermatitis,

some of them showed resistance to topical steroids and

were even exacerbated by application of steroids, so it is

likely that long term topical use of steroids may

modulate the barrier-immunity function of the skin.

The present study compared the efficacy of up to two

weeks treatment with 1% and 2% licorice extract as a

herbal gel with placebo in patients with a clinical

diagnosis of atopic dermatitis.

A total of 108 patients were recruited in the present

study by a single investigator. 18 patients were

excluded from the efficacy analyses. Nine patients

were given systemic antibiotics, five patients were

pregnant, one patient was a nursing mother and

three patients were suffering from other skin disorders.

All of the 90 evaluable subjects complete two weeks

treatment. Table II shows patient characteristics in

several groups.

The assessment of the overall clinical responses,

relative to baseline, at the end of treatment after one

and two weeks is shown in Figure 1. Treatment with 1%

(F9) and 2% (F17) licorice gel resulted in a statistically

significant reduction in the scores for erythema after

two weeks (p,0.05). This effect was not observed for

1% extract gel after one week (pw0.05). The 2% licorice

gel showed more reduction in the scores for erythema

than 1% extract at the end of first and second weeks

(p,0.05). The licorice extract treatment was significantly

more effective than baseline in reducing the

scores for oedema and itching after one week (p,0.05)

and two weeks (p,0.01), and 2% licorice gel was more

effective than 1% extract at the end of first and second

weeks (p,0.05). Treatment with licorice extract was

not significantly effective in reducing the scores of

scaling (pw0.05). The effect of 1% and 2% licorice gel

in reducing in reducing the scores for erythema, oedema

and itching were significantly more than placebo after

one and two weeks (p,0.01).

Baseline evaluation showed that treatment groups

were well balanced in respect of number per group, age

and sex distribution, previous eczema treatment and

severity of signs and symptoms of eczema.

At the end of the treatments, the reduction of

erythema scores was 35.02% for 1% licorice extract

and 60.76% for 2% licorice gel. The reduction of

oedema scores was 56.64% and 83.76% for 1% and 2%

licorice gel treatment after two weeks respectively. At

the end of the treatments, the reduction of itching

scores was 44.1% and 72.53% for 1% and 2% licorice

gel respectively. A study carried out in 1994 reinforced

the excellent reputation of Glycyrrhiza glabra in atopic

dermatitis. Thirty-seven children were given a Chinese

herbal medicine containing licorice (and some other

plants) orally. After one year, 18 of the children had

experienced at least a 90% reduction in their symptoms.

6 Another study showed that topical steroids

exacerbated the dermatitis in about one third of the

patients15 but no side effects were observed in treatment

with licorice topical gel.

Licorice extract

(1%)

Licorice extract

(2%)

Placebo

Age

Mean 32.7 34.1 35.3

Range 16–51 16–49 17–53

Sex

Male 13 12 10

Female 17 18 20

Duration of eczema (years)

Mean 3.8 3.5 3.6

Range 0.01–25 0.01–21 0.01–25

Area of eczema

Head and neck 8 9 7

Trunk 3 2 2

Hands 18 19 19

Feet 1 – 2

Table II

The comparison of patient characteristics

M Saeedi et al The treatment of atopic dermatitis 155

Conclusion

Finally we would like to summarize the current approach

with regard to the management of atopic dermatitis. The

final goal of the treatment is to give patients the

opportunity for improved social activities in their daily

life. Skin care, control of pruritus and exclusion of the

exacerbating factors are three facets of the therapy and the

appropriate use of topical licorice preparations in considering

the patients’ response to this excellent therapeutic tool.

The use of 2% licorice extract gives satisfactory effects in

treatment of atopic dermatitis.

References

1. Swerlick RA, Lawley TJ, Eczema, psoriasis, cutaneous

infection, acne, and other common skin disorders. In:

Fauci AS, Braunwald E, Isselbacher KJ, Wilson JD,

Martin JB, Kasper DL, Hauser SL, Longo DL (eds).

Harrison’s principles of internal medicine, Mc. Grow-Hill:

New York, 1998, pp: 298.

2. Hanifin JM, Critical evaluation of food and mite allergy

in the management of atopic dermatitis. J. Dermatol.

(1997) 24: 495–503.

3. Lane AT, Efficacy and safety of topical steroids in

pediatric atopic dermatitis. J. Eur. Acad. Dermatol.

Venerol. (1997) 8(suppl.): S24–S27.

Figure 1

Investigator assessment of overall clinical response, A: Erythema scores, B: Oedema scores, C: Scaling scores, D: Itching scores.

156 M Saeedi et al The treatment of atopic dermatitis

4. Ramsay CA, Savoie JM, Gilbert M, Gidon M, Kidson P,

The treatment of atopic dermatitis with topical fusidic

acid and hydrocortisone acetate. J. Eur. Acad. Dermatol.

Venerol. (1996) 7(suppl. 1): S15–S22.

5. Sheehan MP, Atherton DJ, A controlled trial of

traditional Chinese medicinal plants in wide spread

non-exudative atopic eczema. Br. J. Dermatol. (1992)

126: 179–184.

6. Sheehan MP, Atherton DJ, One-year follow up to

children treated with Chinese medicinal herbs for

atopic eczema. Br. J. Dermatol. (1994) 130: 488–493.

7. Tamir S, Eizenberg M, Somjen D, Izrael S, Vaya J,

Estrogen-like activity of glabrene and other constituents

isolated from licorice root. J. Steroid Biochem. Mol. Bio.

(2001) 78: 291–298.

8. Leung AY, Foster S., Encyclopedia of common natural

ingredients used in food, drugs and cosmetics, Wiley

Interscience: USA, 1996, pp: 346–348.

9. Yuan R, Lin Y, Traditional Chinese medicine: an

approach to scientific proof and clinical validation.

Pharmacology & Therapeutics. (2000) 86: 191–198.

10. Khaksa G, Zolfaghari ME, Dehpour AR, Samadian T,

Anti-inflammatory and anti-nociceptive activity of disodium

glycyrrhetinic acid and hemiphtalate. Planta Med.

(1996) 62: 326–328.

11. Pisanty S, Segal R, Glycyrrhizin as a vehicle for

iodoxuridine. J. Clin. Pharm. Ther. (1987) 12(Jun):

165–171.

12. Pizzorno J, Textbook of natural medicine. 2nd edn.

Macmillan Press: London, 1999, pp: 767–772.

13. Znakov T, Determination of glycyrrhizic acid in licorice

root extracts. Med. Prom. SSSR. (1963) 4: 35.

14. Atakan N, Erdem C, The efficacy, tolerability and safety

of a new oral formulation of Sandimum– Sandimum

Neoral in severe refractory atopic dermatitis. J. Eur.

Acad. Dermatol. Venerol. (1998) 240–246.

15. Katayama I, Taniguchi H, Matsunaga T, Yokozeki H,

Nishioka K, Evaluation of non-steroidal ointment

therapy for adult type atopic dermatitis. J. Dermatol.

Sci. (1997) 14: 37–44.

M Saeedi et al The treatment of atopic dermatitis 157

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