KR20160037791A - A acidic external application for psoriasis treatment - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for the treatment of psoriasis, which is characterized in that the pH is controlled to be acidic by an acidic polymer compound and is effective for treating psoriasis such as skin thickness reduction, Thereby providing a novel composition for treating psoriasis.

Description

[0001] The present invention relates to an acidic external application for psoriasis treatment,

The present invention relates to a pharmaceutical composition for treating psoriasis, wherein the pH is controlled by an acidic polymer compound.

Psoriasis is a chronic inflammatory skin disease that is a chronic skin disease characterized by the occurrence of peptic peeling that occurs mainly in the elbows, knees, scalp, nails, claws or trunk and peels in silver. Typical forms are psoriatic psoriasis, watery psoriasis, psoriatic psoriasis, or pustular psoriasis, and may occur locally, lightly, or throughout the body, leading to severity and complications.

Research on the causes of psoriasis has been actively carried out, but it is not yet clear. It is a major cause of genetic, environmental, drug, skin irritation, and stress. It stimulates keratinocytes of skin through various mechanisms of immune substances secreted by immune cells such as T cells, dendritic cells and neutrophils of skin, And it is thought that psoriasis occurs due to excessive proliferation and inflammation.

In the treatment of psoriasis, various methods are used, such as directly administering drugs to the onset area, photochemical treatment using ultraviolet light, injecting drugs, or taking drugs that can be taken orally. Directly applied drugs can cause resistance to creams or ointments containing steroids, and photochemical treatment can increase skin aging and skin cancer incidence. In addition, it is known that the therapeutic agent for injection or oral ingestion has side effects such as inhibition of immune cell activity, cirrhosis and fibrosis. To improve these side effects, research into the development of a biological agent as a therapeutic agent for psoriasis is also active, but there is no therapeutic agent or method for preventing a clear cure and recurrence of psoriasis.

Korea Patent No. 0634397 discloses a composition for treating psoriasis in which various ingredients are mixed at specific ratios. Korean Pat. No. 1374907 discloses that alpha 2 adrenergic receptor is provided as a therapeutic agent for psoriasis-related symptoms, and the effect of gross symptom relief The degree of the possibility as a therapeutic agent for psoriasis-related diseases is described.

The present invention relates to a composition for treating psoriasis by controlling the pH to acidic, and there is no known invention for a composition for treating psoriasis through pH control as in the present invention.

Korea Patent No. 0634397 Korea Patent No. 1374907

The present invention provides a composition for the treatment of psoriasis, and more particularly, to provide an acidic pharmaceutical composition for external application having a pH of 3.0 to 5.0 by adjusting pH with an acidic polymer.

The present invention provides a pharmaceutical composition for external use for psoriasis comprising an acidic polymer compound.

The present invention provides a pharmaceutical composition for external use for the treatment of psoriasis whose pH is adjusted to 3.0 to 5.0 by the content of the acidic polymer compound.

The present invention provides an acidic pharmaceutical composition for external application wherein the pH of a carbomer having a carboxyl group is controlled to have a pH of 3.0 to 5.0.

It is effective in the treatment of psoriasis through reduction of skin thickness, reduction of skin moisture evaporation, increase of skin moisture content and measurement of weight loss of skin tissue in the treatment of pharmaceutical composition containing pH 3.0 to 5.0 containing acidic polymeric compound .

Figure 1 shows changes in weight of mice on days 8, 10 and 12.
Fig. 2 shows changes in skin moisture evaporation on mice at 8, 10 and 12 days.
Fig. 3 shows changes in the skin moisture content of the mice on days 8, 10 and 12.
Figure 4 shows changes in the dorsal skin thickness of the mice on days 8, 10 and 12.
Figure 5 shows changes in the skin thickness of the ear of the mice on days 8, 10 and 12.
Figure 6 shows changes in isometric weight of the mice.
Fig. 7 shows changes in the weight of the ear tissue of the mouse. The left bar represents the weight of the left ear.
Figure 8 shows changes in the skin pH of the mice
9 shows the results of erythema measurement of the mouse.
Fig. 10 shows changes in the isotonic epidermal layer thickness of the mice.
Fig. 11 shows changes in thickness of the ear tissue skin layer of the mouse.
12 is a result of observing the thickness of the back tissue (A) and the ear tissue (B) of Comparative Example 1. Fig.
Fig. 13 shows the results of observing the thickness of the back tissue (A) and the ear tissue (B) of Comparative Example 2. Fig.
Fig. 14 shows the results of observing the thickness of the back tissue (A) and ear tissue (B) in Example 1. Fig.
Fig. 15 shows the results of observing the thickness of the back tissue (A) and the ear tissue (B) in Example 2. Fig.
Fig. 16 shows the results of observing the thickness of the back tissue (A) and the ear tissue (B) in Example 3. Fig.
17 shows the results of observing the thickness of the back tissue (A) and the ear tissue (B) in Example 4. Fig.
18 shows the results of observing the thickness of the back tissue (A) and the ear tissue (B) in Example 5. Fig.

Hereinafter, the present invention will be described in detail. The terms used in the present specification should be construed as generally understood by a person having ordinary skill in the art unless otherwise defined. It is to be understood that the drawings and embodiments are not intended to limit the scope of the present invention, which is not intended to limit the scope of the present invention. It is not.

The present invention provides a pharmaceutical composition for external use for the treatment of psoriasis, which comprises an acidic polymer compound and is adjusted to a pH of 3.0 to 5.0 by the acidic polymer compound.

Prosiasis will generally include known psoriasis, diseases with symptoms thereof. Psoriasis is a chronic inflammatory skin disease, characterized by epidermal hyperplasia and inflammation of the dermis, histologically, reddening of the skin at the onset and skin keratin like scales of the skin are observed. Depending on the onset type, psoriasis, And dryness.

The acidic polymer compound is not limited as long as it is a polymer compound containing an acidic functional group and can be used in a pharmaceutical composition. The acidic polymer compound is preferably a carbomer or carbopol. According to one embodiment of the present invention, the pH of the composition can be controlled according to the content of the carbomer, which is an acidic polymer compound having a carboxyl group by polymerizing acrylic acid with a monomer.

The pharmaceutical composition for treating psoriasis is a composition having a specific pH, wherein the pH is in the range of 3.0 to 5.0, 3.1 to 4.9, 3.2 to 4.8, 3.3 to 4.7, 3.4 to 4.6, 3.5 to 4.5, 3.6 to 4.4, 3.7 to 4.3, 3.8 To 4.2, 3.9 to 4.1, 3.1 to 3.9, 3.2 to 3.8, 3.3 to 3.7, and 3.4 to 3.6. The composition for external application of the above-mentioned pH range is applied to psoriasis-induced skin, so that the effect of treating psoriasis according to the decrease of pH can be confirmed. If the pH is less than 3.0, problems such as shape problems may occur and it is difficult to carry out animal experiments, and even when used as an external preparation, adverse effects are exerted on the skin. In addition, the external preparation for skin application having a pH of less than 3.0, which deviates from the pH range specified in the cosmetics standards and test methods of the Food and Drug Administration for the treatment of psoriasis, is in the range of 3.0 to 9.0, which is not meaningful either for experiment or for commercial purposes.

The external preparation is used outside the human body and may be ointment, lotion, cream or the like depending on the formulation, but it is not limited depending on the form as long as it can be used for external treatment. When formulating with an ointment, skin temperature, pH, water content, and amount of lipid should be taken into account. It should be kept in a stable state such as petrolatum, paraffin, plastic, rod, silicone, vegetable oil, wax and lanolin, emulsifiable base, Etc., and may include additives such as antioxidants, preservatives, moisturizers, solubilizers, softening aids, and the like. In the case of lotion-free formulation, it may be formulated into a solution type base, a suspension type base and an emulsion type base, and may include a wetting agent such as glycerin and glycol.

Psoriasis can be induced by applying imiquimod cream to the skin. Psoriasis induced by qi-mode shows clinical, histological and immunological changes similar to those of psoriasis. In order to confirm the effect of the composition for external application for psoriasis in the present invention, psoriasis model induced by qi-mode was used, but not limited thereto, it can be applied to skin of patients with psoriasis.

According to one embodiment of the present invention, when applied to psoriasis-causing skin, the composition for external treatment for psoriasis of acidic condition reduces the pH of the skin, decreases psoriasis-induced epidermal layer thickness of the back and ears, decreases moisture evaporation amount, We could confirm the effect by weight reduction of tissue.

Hereinafter, the composition for external application for psoriasis according to the present invention will be described in more detail with reference to Examples, but the present invention is not limited by the following Examples.

[ Example  1-5]

Acid external preparation for skin application

The external preparation for skin application was prepared in the form of cream which is easy to apply to the skin. The ingredients of the pH 3.5 external preparation are as shown in Table 1 below, and an external preparation for external application of pH 3.0 to 5.0 was prepared by using the same ingredients by adjusting the carbomer and water.

[Table 1]

psoriasis  Making of mouse model

Seven-week-old female mice (Balb / c) were adapted for one week in constant temperature and humidity conditions to prepare psoriatic mice, and 8-week-old mice were prepared. The dorsal hairs of the mouse were epilated and 62.5 mg of imiquimod (Aldara®) 5% cream was applied twice a day and morning to the right ear and sensitized. After 2 days, imiquimode 5% cream was applied to the right ear for 62 days with 62.5 mg each day for 5 days. On the eighth day after the start of the experiment, psoriasis-induced mice were identified by measuring body weight, trans epidermal water loss (TEWL), skin hydration, and skin thickness of the ear.

Comparative Example  1 to 2 and Example  Selection of 1 ~ 5

The body weight of the mouse, the amount of evaporation of the skin level, the amount of skin moisture, the thickness of the skin of the ear, and the skin thickness of the ear were measured, and groups were averaged. Five groups of mice were used in each group. (Comparative Example 1), which is a normal mouse group in which psoriasis has not been induced, and Group 1 (Comparative Example 2), in which psoriasis-induced mice were treated only with IMQ (Imidazoline quaternary) Were defined as the control group, respectively. PH 3.5 external preparation treatment group (Example 3), pH 4.5 external preparation treatment group (Example 2), pH 4.0 external preparation treatment group (Example 3), pH 4.5 external preparation treatment group (Example 1) Example 4), pH 5.0 external preparation treatment group (Example 5).

Application of acidic external agent for skin application and check of condition

On the 8th day after the start of the experiment, the external preparation was applied to the back and right ear for 4 days. On the 8th, 10th, and 12th day of the experiment, the body weight, the amount of skin moisture evaporation, the amount of skin moisture, and the skin thickness of the ear and ear were measured and the skin pH, erytheme was measured from the 12th day And the state was confirmed.

Histopathological confirmation

On the 12th day after the end of the experiment, the mouse was euthanized, and the dorsal skin tissue and the left and right ear tissues were cut into a 6 mm diameter circle, and weighed and fixed in 10% neutral buffered formalin. Paraffin blocks were prepared using fixed tissues and stained with H & E (hematoxylin & eosin) at a thickness of 5 μm. The stained tissue was confirmed by optical microscope (Figs. 12 to 18) and the thickness of the epidermis was measured.

[Table 2]

Table 2 and Figure 1 show the body weight (g) of the mouse, which showed a slight weight loss in the group treated with IMQ, but not so much as to show a significant difference.

[Table 3]

Table 3 and FIG. 2 show the skin moisture evaporation amount (g / cm 2 / hr). In the case of Comparative Example 2 treated with IMQ, the skin moisture evaporation amount was increased more than 5 times on the eighth day compared with Comparative Example 1, 3 and Example 4, and the most excellent effect was obtained in Example 3. A significant increase in all of Examples 1 to 5 was confirmed.

[Table 4]

Table 4 and FIG. 3 show the skin moisture content (AU). In Comparative Example 2 treated with IMQ, the skin moisture content was reduced more than three times as compared with Comparative Example 1, and in Example 2, Example 3 and Example 4, , And the most excellent effect was obtained in Example 3. A significant increase in all of Examples 1 to 5 was confirmed.

[Table 5]

Table 5 and FIG. 4 show the results of measurement of the back thickness (mu m). Comparative Example 2 treated with IMQ showed a thickness three times or more thicker than that of Comparative Example 1, and thicknesses close to normal in Examples 2, 3 and 4 And the best effect was excellent in Example 3. A significant reduction was confirmed in all of Examples 1-5.

[Table 6]

Table 6 and Fig. 5 show the measured ear thickness (占 퐉). The left ear was not treated but the control group. Comparative Example 2 treated with IMQ was thicker than that of Comparative Example 1 by 3 times or more, and a thickness close to normal was shown in Examples 3 and 4, and the most excellent effect was obtained in Example 3. A significant reduction was confirmed in all of Examples 1-5.

[Table 7]

Table 7 and FIG. 6 show the weight (mg) after collecting the back tissues after the completion of the experiment, and the weight was decreased compared with Comparative Example 2 in which IMQ was treated in Examples 1 to 5. The values close to normal were shown in Examples 2, 3, and 4, and the best effect was excellent in Example 3. A significant decrease was observed in all of Examples 1 to 5 when compared to Comparative Example 2. [

[Table 8]

Table 8 and FIG. 7 show the results of measuring the weight (mg) of the ear tissue after the end of the experiment. When compared through the right ear, in Examples 1 to 5, the weight decreased compared with Comparative Example 2 treated with IMQ. The values close to normal were shown in Examples 2, 3 and 4, and a significant decrease was observed in all of Examples 1 to 5 as compared with Comparative Example 2. [

[Table 9]

Table 9 and Fig. 8 show the pH of the skin, showing a decrease in pH in Examples 1 to 5 and a significant decrease except for Example 5, and the closest value to that in Example 3 was found .

[Table 10]

Table 10 and FIG. 9 show erythema levels measured using a colorimeter. The degree of erythema was difficult to distinguish from the naked eye, but decreased to a numerical value. Significance was shown in Examples 3 and 4.

[Table 11]

Table 11 and FIG. 10 show the epidermal thickness (占 퐉) through H & E staining. After photographing the dyed tissue sample, the thickness of the epidermal layer was measured at six different points. Compared with Comparative Example 2 in which IMQ was treated, Examples 1 to 5 showed a significant decrease, and values close to normal were obtained in Examples 3, 4 and 5, and the best effect Respectively.

[Table 12]

Table 12 and Fig. 11 show the epidermal thickness (占 퐉) through H & E staining. After photographing the dyed tissue samples, the thickness of the epidermal layer was measured at six different points. Compared with Comparative Example 2 in which IMQ was treated, Examples 1 to 5 showed a significant decrease, and values close to normal were obtained in Examples 3, 4 and 5, Respectively.

[Table 13]

Table 13 shows the significance of the respective quantitative measurement values measured in Comparative Examples 1 and 2 and Examples 1 to 5. In particular, in Examples 1 to 5, the values of significance There was an effect.

Claims (4)

A composition for external use for psoriasis, which comprises an acidic polymer compound and has a pH of 3.0 to 5.0. The method according to claim 1,
Wherein the pH of the composition is adjusted according to the content of the acidic polymer compound. 3. The method of claim 2,
Wherein the acidic polymer compound is a carbomer or a carbopol. 4. The method according to any one of claims 1 to 3,
Wherein the composition is in a form selected from the group consisting of lotions, creams, gels, ointments, ointments, emulsions, solutions, aerosols and pastes.

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