MLE (multi lamellar emulsion), made from the synthetic ceramide PC-9, which is similar to natural ceramides, is an exact recreation of intercellular lipid layers. MLE is a drug delivery system that, upon application, enters stratum corneum with ease, reinforces skin barrier function, releases the drug over a reasonable amount of time by staying in the epidermis, and thereby increases the drug’s effectiveness and reduces the side effects.

Inflammatory skin condition

Atopic dermatitis

Contact dermatitis

Seborrheic dermatitis

local corticosteroids

Increasedanti-inflammatory effects

Improved release of chemicalagents from the stratum corneum

Prevention of damage in skin barrier Increased production of AMPs

Increased production ofanti-microbial peptide(AMPs)

Increased treatmenteffects of steroids

Prevention ofsecondary infection

Anti-inflammation

Reduction in intercellular lipidsin dead skin cells

Reduction in AMPs production

Increase in infections

Damages in the skin barrier

Increase in inflammation

Treatment effect of local corticosteroids Side effects of local corticosteroids regarding skin conditions and skinbarrier function

Sheu HM, et al., British J Dermatol 1997; 136:884-890Kao JS, et al., J Invest Dermatol 2003; 120:4456-464

MometasoneMLE

In the case of corticosteroids, an increase in effectiveness inevitably results in an increase in side

effects. Thus minimizing side effects can be called an underlying goal of cosmetic corticosteroids.

Stratum corneum, the outermost layer of the skin, is in charge of protecting the skin from harmful

factors and plays a vital role in maintaining an adequate level of moisture. Stratum corneum is

composed of corneous cells and intercellular lipids, which act as the skin barrier.

Side effects have been reduced once more due to the combination

of mometasone, a safe steroid whose side effects were already

minimized, and MLE technology.Dermotasone

Synthesis inhibition of lipidsin the corium derma

allergen allergen various bacteria various bacteria

stra

tum

cor

neum

epid

erm

isde

rma

moisture

epid

erm

isde

rma

moisture

allergen various bacteria

epid

erm

isde

rma

moisture

<Atopic/sensitive skin with damaged skin barrier> <Absorption of MLE by damaged skin barrier> <Healthy skin restored by MLE>

▶Test subjects

Species: Hairless mouse (hairless mice are widely used in animal testing because their skin structure is very similar to

that of human skin)

▶Procedure

a. Day 0- After their TEWL, hydration and thickness are measured, they are grouped according to their TEWL values.

b. After grouping, the drug is applied to them at 9:00AM and at 17:00PM.

c. The steps above are repeated until the morning of day 2.

d. Day 3 - Their TEWL, hydration and thickness are measured again.

Estimating TEWL (Transepidermal Water Loss)▶TEWL amount: A measure of the amount of moisture evaporated from the skin excluding the amount caused by sweating.

Indicates epidermal permeability barrier function.

▶Most commonly used method to measure skin barrier function

▶The normal range for TEWL is between 0.1~0.4mg/m2. It is proportionate to the amount of damage to epidermal permeability

barrier caused by damages to the stratum corneum.

▶Measuring apparatus: TEWameter TM 300 (Courage & Khazaka, Cologne, Germany)

Measuring the moisture level in the stratum corneum▶Measuring the level of moisture in the stratum corneum using the skin capacitance

▶Measuring apparatus: Corneometer CM 820 (Courage & Khazaka, Cologne, Germany)

Testing procedure

Estimation of level of skin barrier damage

Measuring the moisture level

Normal MLE CreamMLE Lotion Existing CreamExisting Lotion

Normal MLE CreamMLE Lotion Existing CreamExisting Lotion

20

15

10

5

03 Day

80

75

70

65

60

553 Day

Contains similar ceramide for patients of age 4 and above with eczematous skin conditions. A manifold for evaluating Mometasone MLE Creamʼs effectiveness of treatment and skin barrier function, double blind test, anda comparative clinical study with Methylprednisolone aceponate 0.1%

Primary effectiveness Evaluation results: PGA treatment success rate

Primary Effectiveness Evaluation Variable: PGA Treatment Success Rate

Primary effectiveness evaluation (PGA) results show that Dermotasone MLE Cream statistically superior to its competition

PGA Effectiveness Rating: (# of Patients considered fully recovered or

improved by PGA standards / Total # of Patients) X 100(%)

▶ Patients: 175 individuals aged 4 and above with symmetrical eczema lesion

▶ Product: Dermotasone MLE Cream

▶ Product compared: Methylprednisolone aceponate 0.1%

▶ Treatment period: At most 2 weeks

▶ Effectiveness evaluation variable

Primary effectiveness evaluation variable: PGA improvement factor

Secondary effectiveness evaluation variable: transepidermal water loss, itch VAS improvement factor

▶ Clinical study site: Myung-Ji Hospital, Yonsei University Hospital, Seoul University Hospital, Gangnam Sungshim Hospital, Incheon Sungmo Hospital

▶ Duration: 11/19/2009, 6/15/2010

Day 15 Full recovery

Improvement

Protection

Stability

Worsening

Total

Effective 1)

90% C.I.2)

1) Full recovery or Improvement

2) 90% confidence interval for difference between two groups computed from matched-pairs table

72(45.28%)

47(29.56%)

28(17.61%)

12(7.55%)

-

159(100.0%)

119(74.84%)

(20.08%, 34.01%)

DermotasoneMLE

(N=159)

Methylprednisoloneaceponate 0.1%

(N=159)

Methylprednisoloneaceponate 0.1%

(N=165)

PP ITT=LOCF

DermotasoneMLE

(N=165)

72(43.64%)

47(28.48%)

31(18.79%)

15(9.09%)

-

165(100.0%)

119(72.12%)

(19.31%, 32.81%)

28(17.61%)

48(30.19%)

61(38.36%)

22(13.84%)

-

159(100.0%)

76(47.80%)

28(16.97%)

48(29.09%)

63(38.18%)

25(15.15%)

-

1(0.61%)

165(100.0%)

76(46.06%)

Methylprednisoloneaceponate 0.1%

Dermotasone MLE 100

80

60

40

20

0Day 4 Day 8 Day 15

ResearchSubject

PGA Improvement Factor : treatment success rate of

the overall evaluation of the patient’s clinical response upon completion

of clinical study

PGA Evaluation: After rating the patient on scaling, erythema,

vesiculation, pruritus, and burning/pain each on a scale of 0 through 2,

the five ratings are added up to produce a final sum. (0: No symptoms,

1: Mild, 2: Medium, 3: Severe)

Evaluation Results and Standards• Full Recovery: Symptom Improvement 100%

• Improvement: Symptom Improvement over 75%

• Protection: Symptom Improvement over 50%

• Stability: Symptom Improvement below 50%

• Worsening: Symptom Worsening

Study Design

Secondary Effectiveness Evaluation Variable: TEWL

Secondary Effectiveness Evaluation Variable: VAS Improvement Factor

Results of TEWL measurements.

After four days of using Dermotasone MLE, the experimental group showed a statistically significant improvement when

compared to the control group.

Results of VAS measurements

After two weeks of using Dermatasone MLE, the experimental group showed a statistically significant improvement when

compared to the control group.

Multi-component clinical testing of eczema patients four years or older - Dermotasone MLE, the experimental drug, when compared to the Reference drug,

Mometasone furoate in MLE (Dermotasone MLETM) in Eczema Treatment

- displayed statistically significant superiority in the primary effectiveness evaluation variable PGA improvement rate,

- and displayed statistically significant superiority in the secondary effectiveness evaluation variables TEWL and VAS.

- No adverse drug reactions or other serious reactions resulted from either the experimental drug or the control drug.

Dermotasone MLE cream showed statistically significant effectiveness results in treating eczema. No unusual adverse drug reactions were found besides the ones that exist in the Reference drug and other existing external steroid medications.

Methylprednisoloneaceponate 0.1%

Dermotasone MLE 100

80

60

40

20

0

(%)

Day 4

TEWL Improvement Factor of Per Protocol group

VAS Improvement Factor of Per Protocol group

Day 8 Day 15

17.12%

16.02%

23.63%32.74%

29.86%

48.30%

P-value=0.0070

P-value=0.0001

P-value=0.0001

Methylprednisoloneaceponate 0.1%

Dermotasone MLE 100

80

60

40

20

0

(%)

Day 4 Day 8 Day 15

40.56%

37.46%

61.22%

75.41%65.38%

83.28%

P-value=0.0001

Trans-epidermal water loss: TEWL- Measure TEWL with TEWameter

- Improvement Factor (%) = [(TEWLday1-TEWL각 visit)/TEWLday1]X100(%)

Itch Scale (VAS)- The change in itchiness in the test subject between the baseline

and the end of the test.

- Improvement Factor (%) = [(VASday1-VAS각 visit)/VASday1]X100(%)

Test ResultSummary

✽✽

✽✽

✽✽

✽✽

Dermotasone cream once a day VSFluocinolone acetonide 0.025%Three times a day

Dermotasone cream once a day VSTriamcinolone acetonide 0.1% Twice a day

No. of patientstreated(evaluated)

Treatment outcomedecrease in total sign andsymptom severity score(%)

Treatment X Duration(wk)

In children(aged between 6mo and 12y)

r, db, pg

nb

r, db

r, nb

21

5

5

5

24

24

5

11

10

12

12

Studydesign

Duration(days)

No. ofsubjects

Effect on serumcortisol levels

MOM

HYDV

MOM

CLO

MOM

HYD

0.1% cr od X≤ 3

0.2% cr bid X≤ 3

0.1% cr od X 3

0.05% cr bid X 3

0.1% cr od X ≤ 6

1.0% cr bid X ≤ 6

111

112

30(30)

30(30)

24(23)

24(19)

87.2

78.6

86.1

66.1

95

75

bid=twice daily; CLO=clobetasone; cr=cream; HYD=hydrocortisone; HYDV=hydrocortisone valerate; MOM=mometasone; od=once daily; p≤0.001 vs comparator

< STUDY 1 > < STUDY 2 >

< STUDY 1 >

< STUDY 2 >

Decr

ease

in to

tal s

ign

and

sym

ptom

sco

re(%

)

Duration of treatment (days)

MOM(n=109)

FLU(n=109)

**P<0.001 vs comparator

MOM 0.1% ung od 15g/day

HYDB 1.0% ung od 15g/day

MOM 0.1% ung 10g/day(20h/day)a

MOM 0.1% ung 30g/day(22h/day)a

MPA 0.1% ung 30g/day(22h/day)a

MOM 0.1% cr 16g/day(11h/day)a

HYDB 0.1% cr 16g/day(11h/day)a

MOM ≡ HYDB

No effect on serum cortisol levels

MOM ≡ MPA

MOM > HYDB

a:Application under airtight occlusion.cr=cream; db=double-blind; HYDB=hydrocortisone butyrate; MOM=mometasone; MPA=methylprednisolone aceponate; nb=nonblind; od=once daily; pg=parallel group; r=randomised; ung=ointment; ≡indicates similar effect; > indicates significantly greater effect.

Treatment

▶ Atopic dermatitis

▶ Psoriasis vulgaris

▶ The Impact of Momerasone on HPA Axis

60

50

40

30

20

10

4 8 15 22

Duration of treatment (days)

MOM(n=66)

TRI(n=66)60

50

40

30

20

10

4 8 15 22

Potent

Safe

Active Ingredient/Dose

Appearance

Effect

Directions

Storage

Packing Unit

Drug Information

Dongkoo products Guide to potencies of topical corticosteroids

Group Generic Name Brand Name

In 1g, Mometasone Furoate --- 1mg

Cream - Complete uniform white cream

Lotion - White or light brown lotion

Alleviation of itch and inflammation from skin conditions in reaction to corticoids

Directions: Once daily, apply small amount to affected area and lightly rub until it fully permeates.

Refrain from putting bandages on the area.

Storage: Airtight container, 1~30°C

cream-15g, 30g, 500g

lotion-30g

1) Drugs. 1998 Jan; 55(1): 145-632) Australas J Dermatol. 1991; 32(2): 85-913) J Am Acad Dermatol. 1991 Apr; 24(4): 603-74) Cutis 1988 Nov; 42(5): 480-5, 1996 Feb;57:13-185) N Z Med J. 1993 May 26; 106(956): 203-56) J Int Med Res. 1990 Nov-Dec; 18(6): 460-77) Today's Therapeutic Trends 1988; 5: 25-35, 1990;8(3):21-348) Drug Saf 1994; 10(5): 406-129) Br J Dermatol 1982; 107 Suppl. 23: 24-910) J Steroid Biochem Mol Biol 1993 Feb; 44: 141-511) Skin Pharmacol 1993; 6(3): 187-9212) J Am Acad Dermatol 1993 Oct: 29: 576-8013) Today's Ther Trends 1988; 5(4): 25-3514) Eur J Clin Pharmacol 1995; 48(2): 123-5

15) Skin Res 1990; 32(3): 395-40216) Dermatol Venereol 1993; 2(3): 225-3017) Int J Clin Pharmacol Ther 1995 Apr: 33: 187-918) Int J Dermatol 1989 Jun: 28: 342-419) Z Hautkr 1991; 66(9): 785-720) Br J Dermatol 1995 Jan: 132: 66-821) Schering-Plough Corporation Limited. data on file, November 199722) Proceedings of the 55th Annual Meeting of the American Academy of Dermatology: 1997 Mar 21-26:San Francisco23) Poster presentation in the 19th World Congress of Dermatology, Sydney, Australia, Jun 15-20, 199724) Curr Ther Res 1990 Jul; 48: 128-3925) Am J Clin Dermatol 2002; 3 (1): 47-58

Ref.)

Ultra Ⅰ

Ⅱ

Ⅲ

High

Medium

Mild

Low

Very Low

Ⅳ

Ⅴ

Ⅵ

Ⅶ

Clobetasol propionate 0.05% ointment, solution

Fluocinonide 0.05% cream

Desoximetasone 0.05% gel

Diflucortolone Valerate 0.3%* ointment

Fluticasone Propionate 0.005% ointment

Mometasone furoate 0.1% cream, lotion

Prednicarbate 0.1% ointment

Clobetasone butyrate 0.05% ointment

Prednicarbate 0.25% lotion

Betamethasone Valerate 0.1% cream

Fluticasone Propionate 0.05% cream

Triamcinolone acetonide 0.1% cream

Prednisolone valeroacetate 0.3% cream, lotion

Clobetasone butyrate 0.05% cream

Desonide 0.05% cream, lotion

Alclometasone dipropionate 0.05% cream

Hydrocortisone 1%

Hydrocortisone 2.5%

Domo-horn Solution/Ointment/Cream

Dermotasone MLE Cream/Lotion

Bade Cream

Dongkoo Dermo Lotion

Cordicare Lotion