KR20130012709A - Pharmaceutical composition for treating atopic dermatitis - Google Patents

Abstract

PURPOSE: An external use composition containing adenosylcobalamin and a method for treating a patient with minor atopic dermatitis are provided to effectively treat atopic dermatitis without side effects. CONSTITUTION: An external use composition for treating a patient with minor atopic dermatitis at over 2 to 10 scores of EASI(Eczema Area and Severity Index) contains adenosylcobalamin(coenzyme B12) as an active ingredient. The external use composition is a gel type in which adenosylcobalamin is encapsulated in liposome. The external use composition is topically administered at least four weeks. [Reference numerals] (AA,CC,EE) Score change; (BB) Control drug(n=11); (DD) Control drug(n=34); (FF) 2 weeks; (GG) 4 weeks; (HH) 6 weeks; (II) 8 weeks

Description

Pharmaceutical composition for the treatment of atopic dermatitis {PHARMACEUTICAL COMPOSITION FOR TREATING ATOPIC DERMATITIS}

The present invention provides a method for treating mild atopic dermatitis patients using an external preparation composition containing adenosyl cobalamin as an active ingredient.

Atopic dermatitis is a recurrent chronic dermatitis with severe itching. It is difficult to estimate the exact incidence of atopic dermatitis in Korea, but its prevalence is steadily increasing. Prevalence rates of approximately 10-20% are reported, and varying prevalence rates vary according to region, age, gender, and sociocultural characteristics.

There are several therapeutic agents that can be administered topically to atopic skin lesions. Currently the most commonly used therapeutic agent for the treatment of atopic dermatitis is a steroid preparation. If steroids are used in excess of the dosage, the steroid binding receptors are depleted and become resistant, and patients are forced to apply more often or use more intense ones. Eventually, patients use higher amounts of steroids, which in turn deteriorate the skin as the steroids degenerate from the skin to peroxides. The thinner the skin, the better it is absorbed, especially in children, so the side effects limit the use of steroids.

In addition to steroids, immunomodulators and antihistamines are used, but immunomodulators have less side effects than steroids, but the possibility of skin cancer has been raised. In addition, the use of antihistamines to improve pruritus leads to a vicious cycle of pruritus-scratch-atopic dermatitis-pruritus even though pruritus is improved, making treatment difficult. And no effect has yet been demonstrated for atopic dermatitis. Therefore, it is urgent to develop an effective and safe treatment for atopic dermatitis.

Accordingly, the present applicant has filed a Korean Patent Application No. 2005-0120648 (Registration No. 0658436) for adenosyl cobalamin (coenzyme B12) -containing composition for the treatment of skin diseases. The adenosyl cobalamin-containing external preparation composition is difficult to expect a quick drug, the molecular weight is so large that 90% or more of the dosage is excreted to improve the disadvantages of the existing cobalamin (vitamin B12) formulation showing a very low bioavailability Adenosyl cobalamin constituting cobalamin coenzyme as an active ingredient, and is an external preparation for treating skin diseases that facilitates the penetration of the epidermal barrier of the skin. In particular, the adenosyl cobalamin-containing external preparation composition exhibits an excellent effect on atopic dermatitis.

KR 0658436 B

The present invention confirmed that the external preparation composition containing adenosyl cobalamin as an active ingredient exhibits an excellent therapeutic effect in patients with mild atopic dermatitis.

Therefore, the present invention provides a method for treating mild atopic dermatitis patients by topically administering an external preparation composition containing adenosyl cobalamin as an active ingredient, and an external preparation composition containing adenosyl cobalamin as an active ingredient for treating mild atopic dermatitis. .

In addition, the present invention confirmed that the external preparation composition containing adenosyl cobalamin as an active ingredient shows a superior therapeutic effect to female patients among patients with mild atopic dermatitis.

In another aspect, the present invention provides a method for treating female mild atopic dermatitis patients by topically administering an external preparation composition containing adenosyl cobalamin as an active ingredient, and adenosyl cobalamin for treating mild atopic dermatitis as an active ingredient. The external preparation composition is provided.

The present invention provides a method for treating mild atopic dermatitis patients by topically administering an external preparation composition containing adenosyl cobalamin as an active ingredient.

Atopic dermatitis is a patient diagnosed with atopic dermatitis. In most cases, atopic dermatitis is diagnosed according to clinical symptoms because there is no specific method or test. As an example, Hanifin & Rajka's criteria for diagnosing atopic dermatitis can be used.

Atopic dermatitis can be divided into mild, moderate, and severe according to the severity of symptoms. In the present invention, the Eczema Area and Severity Index (EASI) score change was selected as the primary efficacy endpoint. When classified based on the EASI score, mild is generally 10 or less EASI score, greater than 10 or less 20, and severe more than 20 severe. Mild atopic dermatitis for the present invention is atopic dermatitis with an EASI score greater than 2 and less than 10. An EASI score of less than 2 was excluded because the symptoms of atopic dermatitis were insignificant and the apparent effects of the present invention could not be measured. Thus, a mild atopic dermatitis patient of the present invention refers to atopic dermatitis patients with EASI score greater than 2 and 10 or less when atopic dermatitis is diagnosed.

The external preparation composition containing the adenosyl cobalamin of the present invention as an active ingredient and a method for preparing the same are described in Korean Patent Application No. 2005-0120648 of the applicant, which is incorporated herein by reference. Preferably, the external preparation composition of the present invention is an external preparation composition in the form of a gel in which adenosyl cobalamin is encapsulated in a liposome including phospholipid and cholesterol. If necessary, it may further include a surfactant containing an alkyl group having 8 to 16 carbon atoms for the purpose of enhancing skin absorption and skin affinity. Although not limited thereto, the content of adenosyl cobalamin may be 0.01 to 7 wt% based on the total external composition. In one embodiment, the content of adenosyl cobalamin may be 0.01 to 1% by weight relative to the total external composition.

Administration of the present invention means the thin application of the topical composition of the present invention to atopic dermatitis lesions. As one of the administration methods of the present invention, a thin coating is applied twice a day at intervals of about 8 to 14 hours. As one embodiment, the present invention includes continuous administration of an external preparation composition containing adenosyl cobalamin as an active ingredient for at least 4 weeks, at least 6 weeks, or at least 8 weeks.

As another embodiment, the present invention provides a method for treating mild atopic dermatitis in a female by topically administering an external preparation composition containing adenosyl cobalamin as an active ingredient to a female mild atopic dermatitis patient.

The woman of the present invention is not age-restricted, but in one embodiment, a woman who has started menarche and is generally a woman over 12 years old. Atopic dermatitis is more common in women after puberty ( Osman meat al , Arch Dis Child 2003; 88; 587-590) , in terms of treatment, there are no cases in which the difference between women and men has been identified.

As another embodiment, the present invention provides an external preparation composition containing adenosyl cobalamin for treating mild atopic dermatitis as an active ingredient.

As another embodiment, the present invention provides an external preparation composition containing adenosyl cobalamin for treating mild atopic dermatitis in women as an active ingredient.

In order to confirm the therapeutic effect of the adenosyl cobalamin external composition for atopic dermatitis patients, an eight-week double-blind, randomized, placebo-controlled, parallel group clinical trial was conducted.

A total of 125 patients with mild atopic dermatitis (28 patients with EASI score 2 or lower and EASI score 2 with 0.07% and 0.30% adenosyl cobalamin external gel as a test drug and a gel containing 0.3% nanoliposome except adenosyl cobalamin as a control drug) A total of 37 patients with> 10 or less) and 37 patients with moderate atopic dermatitis (> EASI score> 10) reported changes in EASI score, change in EASI score percentage in patients with mild atopic dermatitis above EASI score> 2, IGA treatment success rate, IGA score change, pruritus, insomnia and quality of life were all significant effects.

In addition, among patients with mild atopic dermatitis above EASI score 2 and below 10, female patients showed superior effects in all of the above assessments compared to male patients.

The present invention can safely and effectively treat patients with mild atopic dermatitis using an external preparation composition containing adenosyl cobalamin as an active ingredient.

1 is a graph showing changes in EASI score in patients with (i) EASI score 2 or less, (ii) EASI score greater than 2 or less and (iii) EASI score greater than or equal to 10, atopic dermatitis, measured according to the clinical practice of the present invention.
FIG. 2 is a graph showing percent change in EASI score in patients with (i) EASI score 2 or less, (ii) EASI score 2 or more and 10 and (iii) EASI score or more and 10 or more atopic dermatitis, measured according to the clinical practice of the present invention. .
FIG. 3 is a graph showing the success rate of IGA treatment in patients with (i) EASI score 2 or less, (ii) EASI score 2 or more and 10 and (iii) EASI score or more and 10 or more atopic dermatitis, measured according to the clinical practice of the present invention.
FIG. 4 is a graph showing IGA score changes in patients with (i) EASI score 2 or less, (ii) EASI score 2 or more and 10 or less and (iii) EASI score or more and 10 or more atopic dermatitis measured according to the clinical practice of the present invention.
FIG. 5 is a graph showing changes in pruritus degree in patients with (i) EASI score 2 or less, (ii) EASI score 2 or more and 10 or less, and (iii) EASI score or more and 10 or more atopic dermatitis, measured according to the clinical practice of the present invention.
FIG. 6 is a graph showing changes in insomnia in patients with (i) EASI score 2 or less, (ii) EASI score 2 or more and 10 or less and (iii) EASI score or more and 10 or more atopic dermatitis measured according to the clinical practice of the present invention.
FIG. 7 is a graph showing changes in quality of life in patients with (i) EASI score 2 or less, (ii) EASI score 2 or more and 10 or less and (iii) EASI score or more and 10 or more atopic dermatitis, measured according to the clinical practice of the present invention. to be.
FIG. 8 is a graph showing the change in EASI score between male and female among patients with atopic dermatitis greater than 2 and less than EASI score 2 according to the clinical practice of the present invention.
9 is a graph showing the percentage change in EASI score between male and female among patients with atopic dermatitis greater than 2 and less than EASI score 2 according to the clinical practice of the present invention.
10 is a graph showing the success rate of IGA treatment between male and female among atopic dermatitis patients with EASI score greater than 2 and less than 10 measured according to the clinical practice of the present invention.
FIG. 11 is a graph showing the change in IGA score between male and female among atopic dermatitis patients with EASI score greater than 2 and less than 10 measured according to the clinical practice of the present invention.
12 is a graph showing the degree of pruritus changes between men and women among atopic dermatitis patients with EASI score greater than 2 and less than 10 measured according to the clinical practice of the present invention.
FIG. 13 is a graph showing changes in insomnia between males and females among atopic dermatitis patients with EASI score greater than 2 and less than 10 measured according to the clinical practice of the present invention.
14 is a graph showing a change in the quality of life between men and women of atopic dermatitis patients with EASI score greater than 2 and less than 10 measured according to the clinical practice of the present invention.

Hereinafter, preferred preparation examples and examples are provided to help understanding of the present invention, but the following preparation examples and examples are merely illustrative of the present invention, and the scope of the present invention is not limited thereto.

[ Manufacturing example  One] Adenosyl cobalamin  0.07% external gel preparation ( Test drug  1 manufacture)

In order to prepare the adenosyl cobalamin external gel of the present invention, it was carried out under the condition that the light is blocked. After putting propylene glycol in a paddle mixer tank, cholesterol and stearoyl phosphatidylcholine were added at a ratio of 1: 3 and stirred to allow complete dissolution. Accurately weigh 35 g of adenosyl cobalamin into a separate container and add it to 3,500 g of purified water, and then completely dissolve the adenosyl cobalamin and put it into the paddle mixing tank. The solution was extruded with a nano disperser (ILSIN autoclave) until particles of 100 nm to 200 nm were obtained to prepare liposomes.

In order to prepare a gel base, purified water and carbomer were added to a homo mixer tank and completely dissolved by stirring. After adding glycerol and sodium edetate hydrate therein, completely dissolving, methyl paraoxybenzoate and propyl paraoxybenzoic acid were added, and a homogeneous mixer was operated to mix until homogeneous. After completion of mixing, the trolamine was added to adjust the pH in the range of 6.5 to 7.5 to prepare a gel base.

The liposome prepared above was put into a mixing tank containing a gel base, and stirred for 30 minutes to prepare 50 kg of test drug 1 containing 0.07% of adenosyl cobalamin.

[ Manufacturing example  2] Adenosyl cobalamin  0.3% external gel preparation ( Test drug  2 manufacturing)

Except that 150 g of adenosyl cobalamin was added to 15,000 g of purified water, 50 kg of the test drug 2 containing 0.3% of adenosyl cobalamin was prepared in the same manner as in Preparation Example 1.

[ Manufacturing example  3] Adenosyl cobalamin  Placebo gel manufacturing (control preparation)

A nanoliposome gel preparation containing no adenosyl cobalamin as a main ingredient in the test drug was prepared as a control drug of the clinical trial. The purpose of this study was to identify only the effect of pure adenosyl cobalamin in atopic dermatitis, so it was set as a control except for adenosyl cobalamin in the test drug. This clinical trial is conducted over a medium-term period of 8 weeks, and steroids, immunosuppressants, etc. have problems in terms of stability, and these are compared with the adenosyl cobalamin external composition as secondary, short-term and intermittent treatments. The reference drug was set as above in an inappropriate relationship.

In addition, this test drug has a reddish color depending on the characteristics of the main ingredient, so that a double-blinded red pigment was added to the reference drug, and the 'Tar pigment designation and standards and test methods for quasi-drugs and cosmetics' were specified. Placebo was made using red 227 and 40 and selected as a control.

[ Example  1] Clinical Protocol

Example  1-1: Criteria for Selection of Clinical Subjects

Men and women aged 12 to 18 years of age who were diagnosed with atopic dermatitis by Hanifin & Rajka were selected. Subjects were selected for mild to moderate atopic dermatitis based on the EASI score. In addition, we set up exclusion criteria for subjects who received drugs requiring a drug release period and those with vitamin B12 allergy.

Example  1-2: test method

At week 0 of the trial (Visit 2), each subject was assigned a random number. Group 1 is assigned to Test 1 (HL-009 0.07%), Test 2 (HL-009 0.30%), and Control: 1: 1: 1. 54 patients and 56 controls were used for a total of 162 patients.

The trial period per subject consisted of 7 visits (screening, 0 weeks, 2 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks), including 10 weeks of screening. After a week-long screening period and the completion of the 8-week treatment period, follow-up visits were made two weeks later to confirm safety. If no extracorporeal discharge period was required, visits 1 and 2 were conducted simultaneously.

Subjects will be admitted once every two weeks during the treatment period following randomization to be prescribed a two-week study drug at each visit 2, 3, 4, or 5, and a blank study prescribed at each visit 3, 4, 5, or 6 Drug tubes and any remaining clinical investigational drugs should be returned.

Example  1-3: Dosage, Duration and Method of Administration

Test drug 1, test drug 2, and the control drug were thinly applied in the following amounts considering the site and area of atopic dermatitis twice a week for about 8 to 14 hours. The squeezed tube for this study drug (1 mm in diameter) corresponds to 0.07 g per cm of gel, which was applied to a body surface area of about 3.3 cm x 3.3 cm.

Moisturizers were applied with steroid-containing moisturizers (Neutrogen, Moisturizer, Johnson & Johnson) twice a day after baseline, up to 8 weeks, appropriately for atopic dermatitis. However, the study drug should be applied at least 30 minutes after application.

Example  1-4: Evaluation Method

In the outpatient department, the investigator evaluated the subject's atopic dermatitis evaluation (EASI and IGA) and safety, and the subject performed pruritus, insomnia and quality of life.

Example  1-5: Validation Variables and Stability Evaluation Variables

The change in EASI score was set as the primary efficacy endpoint in this clinical trial. Secondary efficacy endpoints were assessed as percentage change in EASI score, success rate of IGA treatment, change in IGA score, degree of pruritus, insomnia and quality of life.

1) Change in EASI Score

The body surface area is divided into four areas: head and neck, upper limbs, torso and lower limbs. In each part of the body, the degree of erythema, induration / population, abrasion and lichenification, acute / chronic inflammatory reactions of atopic dermatitis, will be observed, with severity ranging from 0 to 3. It is represented by the numerical value of. In addition, quantify by measuring the surface area of the body showing the above symptoms at four sites. Scores range from 0, where there are no symptoms, to 6, where symptoms appear in 90-100% of the area. Each body part is also weighted according to age. Age groups 8 years and older apply 10% for head and neck, 20% for upper limb, 30% for torso and 40% for lower limb. The body surface area and the symptoms quantified in the above process are multiplied by the ratio according to age, and the combined values are EASI scores, and the values range from 0 to 72 depending on the severity. In this way, the change in EASI score is assessed by measuring the score before and after dosing.

2) EASI score percentage change

The change in EASI score percentage is assessed by percentage of the change in EASI score after administration compared to pre-administration.

3) IGA treatment success rate and IGA score change

The IGA score is given by the researcher's overall evaluation based on the criteria as shown in Table 1 (IGA score) below in 6 steps from 0 to 5 points.

IGA  Score score Symptom 0 = Clear No inflammatory symptoms of atopy 1 = Almost clear Slight perceptual erythema, papulation / infiltration 2 = Mild Mild erythema, papulation / infiltration 3 = Moderate Moderate erythema, papulation / infiltration 4 = Severe Severe erythema,
Papulation / infiltration 5 = Very severe Severe erythema with exudation and swelling,
Papulation / infiltration

IGA treatment success rate is determined by the subject as a treatment success if the IGA score is 0 or 1 at the end of the study start and end.

Change in IGA score assesses the amount of change in IGA score after dosing versus predose.

4) Pruritus and insomnia evaluation

The subject's assessment of pruritus / insomnia is 10 cm VAS (Visual Analog Scale). Evaluate the amount of change after administration compared to pre-administration with a zero point for no itching / insomnia and 10 points for the most severe itching / insomnia.

5) Quality of Life (QOL) Assessment

The assessment of quality of life consists of a total of 10 questions relating to symptoms and perception, leisure and leisure, school or holiday, personal relationships, sleep and treatment. Subjects scored each question "very much (3 points), fairly (2 points), slightly (1 point) and none (0 points)", and added up the scores to assess the amount of change after administration compared to pre-dose do.

[ Example  2] EASI  Comparison of effects by score group (medium vs . Comparison of the Effects of Patients with Moderate Atopic Dermatitis)

The results of confirming the effects on atopic dermatitis patients with EASI score 2 or less, EASI score 2 or more and 10 or less and EASI score or more and 10 or more are as follows. Effects were: EASI score change (Table 2), EASI score percentage change (Table 3), IGA treatment success rate (Table 4), IGA score change (Table 5), pruritus degree (Table 5), insomnia level (Table 6) and life The quality change (Table 7) was confirmed.

EASI  Change score Initial EASI Score
range Experimental group Treatment period 2 weeks 4 weeks 6 weeks 8 weeks 2 or less 0.07% (n = 9) 0.11 0.20 0.11 0.23 0.3% (n = 8) 0.06 0.48 0.38 0.23 Reference drug (n = 11) 0.41 0.58 0.77 0.86 More than 2 more than 10 0.07% (N = 30) 0.42 1.45 1.78 2.17 0.3% (N = 32) 0.38 1.03 1.54 2.09 Reference drug (N = 34) 0.74 0.80 1.19 1.79 More than 10 0.07% (n = 12) 3.23 4.98 5.71 6.84 0.3% (n = 14) 2.29 1.31 2.39 3.45 Reference drug (n = 11) 2.95 4.41 7.22 8.05

EASI  Score percentage change Initial EASI Score
range Experimental group Treatment period 2 weeks 4 weeks 6 weeks 8 weeks 2 or less 0.07% (n = 9) 8.10 19.88 3.39 10.90 0.3% (n = 8) 8.15 23.94 16.24 4.26 Reference drug (n = 11) 28.32 40.41 52.88 60.62 More than 2 more than 10 0.07% (N = 30) 8.51 26.01 32.00 40.01 0.3% (N = 32) 8.61 20.22 27.18 34.57 Reference drug (N = 34) 14.61 16.28 22.95 33.64 More than 10 0.07% (n = 12) 21.52 33.03 36.97 44.71 0.3% (n = 14) 18.97 11.07 23.94 26.91 Reference drug (n = 11) 20.05 29.05 49.75 55.27

IGA  Treatment success rate Initial EASI Score
range Experimental group Treatment period 2 weeks 4 weeks 6 weeks 8 weeks 2 or less 0.07% (n = 9) 11.1 22.2 33.3 66.7 0.3% (n = 8) 12.5 25.0 25.0 25.0 Reference drug (n = 11) 27.3 45.5 63.6 81.8 More than 2 more than 10 0.07% (N = 30) 3.3 10.0 13.3 36.7 0.3% (N = 32) 3.1 6.3 12.5 25.0 Reference drug (N = 34) 8.8 9.1 18.8 23.5 More than 10 0.07% (n = 12) 0.0 0.0 8.3 16.7 0.3% (n = 14) 0.0 0.0 0.0 7.1 Reference drug (n = 11) 0.00 0.00 27.3 18.2

IGA  Change score Initial EASI Score
range Experimental group Treatment period 2 weeks 4 weeks 6 weeks 8 weeks 2 or less 0.07% (n = 9) 0.18 0.55 0.55 1.27 0.3% (n = 8) 0.00 0.00 0.00 0.13 Reference drug (n = 11) 0.27 0.45 0.73 1.00 More than 2 more than 10 0.07% (N = 30) 0.20 0.27 0.43 0.70 0.3% (N = 32) 0.13 0.25 0.28 0.59 Reference drug (N = 34) 0.06 0.12 0.26 0.41 More than 10 0.07% (n = 12) 0.17 0.33 0.58 0.58 0.3% (n = 14) 0.21 0.07 0.21 0.29 Reference drug (n = 11) 0.18 0.45 0.55 0.55

Pruritus degree assessment Initial EASI Score
range Experimental group Treatment period 2 weeks 4 weeks 6 weeks 8 weeks 2 or less 0.07% (n = 8) 0.89 1.61 0.43 1.76 0.3% (n = 8) 0.38 -0.01 0.34 0.85 Reference drug (n = 11) 0.50 1.49 2.09 2.46 More than 2 more than 10 0.07% (N = 30) 1.23 2.13 2.13 2.60 0.3% (N = 32) 0.93 1.52 1.84 2.67 Reference drug (N = 34) 0.95 0.92 1.28 1.65 More than 10 0.07% (n = 12) 0.23 0.49 1.32 1.26 0.3% (n = 13) 0.68 1.33 0.99 1.24 Reference drug (n = 11) 1.88 2.78 2.21 3.01

Insomnia degree evaluation Initial EASI Score
range Experimental group Treatment period 2 weeks 4 weeks 6 weeks 8 weeks 2 or less 0.07% (n = 8) 0.11 0.49 -0.29 -0.03 0.3% (n = 8) -0.08 -0.10 -0.10 -0.14 Reference drug (n = 11) -0.10 0.05 0.27 0.44 More than 2 more than 10 0.07% (N = 30) 0.35 0.55 0.99 1.58 0.3% (N = 32) 0.73 1.05 1.50 1.92 Reference drug (N = 34) 0.53 0.56 0.71 0.96 More than 10 0.07% (n = 12) 0.37 1.57 1.99 2.08 0.3% (n = 13) 0.34 1.38 1.30 1.58 Reference drug (n = 11) 1.06 1.64 1.43 1.61

Assessment of changes in quality of life Initial EASI Score
range Experimental group Treatment period 2 weeks 4 weeks 6 weeks 8 weeks 2 or less 0.07% (n = 9) 0.33 1.00 1.00 2.11 0.3% (n = 8) -0.63 -1.00 -1.13 0.00 Reference drug (n = 11) 2.18 1.82 2.27 3.45 More than 2 more than 10 0.07% (N = 30) 1.58 3.10 3.68 4.68 0.3% (N = 32) 1.25 2.53 3.38 4.06 Reference drug (N = 34) 1.06 1.35 1.53 2.06 More than 10 0.07% (n = 12) 4.58 3.83 5.92 6.83 0.3% (n = 13) 0.92 2.15 1.46 1.15 Reference drug (n = 11) 2.00 3.27 2.82 3.64

As shown in [Table 2] to [Table 8] and [FIGS. 1 to 7] above, the effect of adenosyl cobalamin atopic dermatitis treatment in patients with mild atopic dermatitis greater than or equal to EASI score 2 and less than 10 is EASI score in all items. It can be seen that it is superior to patients with atopic dermatitis of 2 or less and patients with atopic dermatitis with an EASI score greater than 10.

[ Example  3] EASI  Atopic dermatitis above score 2 and below 10 In patients  Comparison of effects between men and women

The effects of atopic dermatitis patients with EASI scores above 2 and below 10 were divided into males and females. Effects were: EASI score change (Table 9), EASI score percentage change (Table 10), IGA treatment success rate (Table 11), IGA score change (Table 12), pruritus degree (Table 13), degree of insomnia (Table 14), and life The quality change (Table 15) was confirmed.

EASI  Change score Gender distinction
(2 <EASI = 10) Experimental group Treatment period 2 weeks 4 weeks 6 weeks 8 weeks female 0.07% (n = 18) 0.64 1.72 2.37 2.73 0.3% (n = 16) 0.34 0.97 1.89 2.67 Reference drug (n = 16) 0.51 0.54 0.89 1.26 male 0.07% (N = 12) 0.08 1.03 0.90 1.34 0.3% (N = 16) 0.41 1.09 1.19 1.51 Reference drug (N = 18) 0.94 1.02 1.45 2.27

EASI  Score percentage change Gender distinction
(2 <EASI = 10) Experimental group Treatment period 2 weeks 4 weeks 6 weeks 8 weeks female 0.07% (n = 18) 13.90 30.45 42.41 48.96 0.3% (n = 16) 7.53 19.52 30.41 42.78 Reference drug (n = 16) 6.19 9.50 14.69 23.59 male 0.07% (N = 12) 0.43 19.35 16.38 26.60 0.3% (N = 16) 9.69 20.92 23.95 26.35 Reference drug (N = 18) 22.09 22.30 30.30 42.58

IGA  Treatment success rate Gender distinction
(2 <EASI = 10) Experimental group Treatment period 2 weeks 4 weeks 6 weeks 8 weeks female 0.07% (n = 18) 5.56 11.11 16.67 50.00 0.3% (n = 16) 0.00 6.25 12.50 31.25 Reference drug (n = 16) 12.50 6.25 18.75 25.00 male 0.07% (N = 12) 0.00 7.69 7.69 15.38 0.3% (N = 16) 6.25 6.25 12.50 18.75 Reference drug (N = 18) 5.56 11.11 16.67 22.22

IGA  Change score Gender distinction
(2 <EASI = 10) Experimental group Treatment period 2 weeks 4 weeks 6 weeks 8 weeks female 0.07% (n = 18) 0.22 0.28 0.50 0.83 0.3% (n = 16) 0.19 0.38 0.38 0.75 Reference drug (n = 16) 0.00 0.00 0.19 0.31 male 0.07% (N = 12) 0.00 0.08 0.15 0.31 0.3% (N = 16) 0.06 0.13 0.19 0.44 Reference drug (N = 18) 0.11 0.22 0.33 0.50

Pruritus degree assessment Gender distinction
(2 <EASI = 10) Experimental group Treatment period 2 weeks 4 weeks 6 weeks 8 weeks female 0.07% (n = 18) 1.20 2.03 2.22 2.47 0.3% (n = 16) 0.86 1.15 1.46 2.54 Reference drug (n = 16) 0.86 0.81 1.08 1.21 male 0.07% (N = 12) 1.23 2.34 1.99 2.80 0.3% (N = 16) 1.01 1.89 2.23 2.79 Reference drug (N = 18) 1.03 1.02 1.46 2.03

Insomnia degree evaluation Gender distinction
(2 <EASI = 10) Experimental group Treatment period 2 weeks 4 weeks 6 weeks 8 weeks female 0.07% (n = 18) 0.74 0.99 1.61 2.18 0.3% (n = 16) 0.11 0.33 1.23 1.67 Reference drug (n = 16) 0.39 0.32 0.54 0.78 male 0.07% (N = 12) -0.43 0.98 0.64 1.17 0.3% (N = 16) 1.27 1.68 1.68 2.04 Reference drug (N = 18) 0.66 0.77 0.86 1.13

Assessment of changes in quality of life Gender distinction
(2 <EASI = 10) Experimental group Treatment period 2 weeks 4 weeks 6 weeks 8 weeks female 0.07% (n = 18) 1.61 3.06 4.33 4.67 0.3% (n = 16) 1.25 2.19 3.13 3.75 Reference drug (n = 16) 0.94 1.13 1.25 1.50 male 0.07% (N = 12) 1.67 3.42 3.00 5.08 0.3% (N = 16) 1.25 2.88 3.63 4.38 Reference drug (N = 18) 1.17 1.56 1.78 2.56

As shown in [Table 9] to [15] and [FIG. 8] to [FIG. 14], the atopic treatment effect of adenosyl cobalamin in atopic dermatitis patients with EASI score greater than 2 or less than 10 was higher in female patients than in male patients. Excellent in all items.

Claims (10)

An external preparation composition containing adenosyl cobalamin as an active ingredient for the treatment of mild atopic dermatitis patients with an EASI score greater than 2 or less than 10. An external preparation composition containing adenosyl cobalamin as an active ingredient for the treatment of female mild atopic dermatitis patients having an EASI score greater than 2 and less than 10. The external preparation composition according to claim 1 or 2, wherein the external preparation composition containing adenosyl cobalamin as an active ingredient is a gel form in which adenosyl cobalamin is encapsulated in a liposome. The external preparation composition according to claim 1 or 2, wherein the external preparation composition containing adenosyl cobalamin as an active ingredient is 0.01 to 7 wt% based on the total external preparation composition. A method for treating mild atopic dermatitis patients having an EASI score greater than 2 and 10 or less by topically administering an external preparation composition containing adenosyl cobalamin as an active ingredient. A method of treating a female mild atopic dermatitis patient having an EASI score greater than 2 and 10 or less by topically administering an external preparation composition containing adenosyl cobalamin as an active ingredient. The method of claim 5 or 6, wherein the topical administration is for at least 4 weeks. The method of claim 5 or 6, wherein the topical administration is for at least six weeks. The method of claim 5 or 6, wherein the topical administration is for at least eight weeks. 7. The method of claim 5 or 6, wherein the topical administration is applied thinly, twice daily, at intervals of about 8 to 14 hours.

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