PAD FOR ALLEVIATING AND TREATING PLASMA PROTEIN EXUDATION SKIN DISEASES INCLUDING ATOPIC DISEASES
20200030480 ยท 2020-01-30
Inventors
Cpc classification
A61K8/9717
HUMAN NECESSITIES
A61F2013/00225
HUMAN NECESSITIES
A61P17/02
HUMAN NECESSITIES
C08L5/12
CHEMISTRY; METALLURGY
A61K36/04
HUMAN NECESSITIES
A61L2300/216
HUMAN NECESSITIES
A61F13/01012
HUMAN NECESSITIES
A61L15/60
HUMAN NECESSITIES
A61F7/02
HUMAN NECESSITIES
A61K31/685
HUMAN NECESSITIES
A61L15/60
HUMAN NECESSITIES
A61F13/00063
HUMAN NECESSITIES
A61L2300/30
HUMAN NECESSITIES
C08L5/12
CHEMISTRY; METALLURGY
International classification
A61L15/40
HUMAN NECESSITIES
A61K36/04
HUMAN NECESSITIES
A61K8/9717
HUMAN NECESSITIES
A61K31/685
HUMAN NECESSITIES
A61L15/42
HUMAN NECESSITIES
A61P17/02
HUMAN NECESSITIES
Abstract
The present invention relates to a pad for treating skin diseases, comprising agar gel and a fiber layer fixed to the inside of the gel, and a manufacturing method therefor. The pad of the present invention inhibits blood vessel exudation symptoms according to vasodilation by maintaining a low temperature of the affected area, reduces an itchy sensation and, at the same time, removes, from the skin, plasma proteins and various plasma-derived substances accumulated in skin tissue, thereby having an effect of alleviating the symptoms of the affected area.
Claims
1. A pad for treating the skin diseases, comprising an agar gel and a fiber layer fixed to the inside of the gel.
2. The pad according to claim 1, wherein the pad further comprises a porous membrane for regulating amounts of the moisture evaporation on the upper surface of the fiber layer.
3. The pad according to claim 2, wherein the pad further comprises a net structure for preventing contact between the clothes and the pad on the upper surface of the porous membrane.
4. The pad according to claim 1, characterized in that the pad further comprises at least one of an organic acid and a salt thereof.
5. The pad for treating skin diseases according to claim 4, characterized in that the organic acid is propionic acid, butyric acid or acetic acid.
6. The pad for treating skin diseases according to claim 1, characterized in that the pad further comprises phospholipids.
7. The pad for treating skin diseases according to claim 6, characterized in that the phospholipid is lecithin.
8. The pad for treating skin diseases according to claim 1, characterized in that the fiber is paper, natural fiber or synthetic fiber.
9. The pad for treating skin diseases according to claim 1, characterized in that the skin disease is a disease showing vascular exudation of plasma proteins.
10. The pad for treating skin diseases according to claim 1, characterized in that the skin disease is a disease selected from the group consisting of atopic dermatitis, eczema, psoriasis, contact dermatitis, and skin pruritus.
11. A pad for applying after mosquito bite, which comprises an agar gel and a fiber layer fixed to the inside of the gel.
12. (canceled)
13. (canceled)
14. A method for preparing a pad for treating skin diseases, comprising steps for placing agar in NaCl solution and sterilizing the solution; placing a fiber on the surface of the solution before the solution is hardened and then curing the solution to be united with agar.
15. The method for preparing the pad for treating skin diseases according to claim 14, characterized in that it further comprises adding at least one of an organic acid and a phospholipid before the solution hardens.
16. The method for preparing the pad for treating skin diseases according to claim 14, characterized in that the fiber is paper, natural fiber or synthetic fiber.
17. The method for preparing the pad for treating skin diseases according to claim 14, characterized in that the skin disease is a disease showing vascular exudation of plasma proteins.
18. The pad for treating skin diseases according to claim 2, characterized in that the skin disease is a disease showing vascular exudation of plasma proteins.
19. The pad for treating skin diseases according to claim 2, characterized in that the skin disease is a disease selected from the group consisting of atopic dermatitis, eczema, psoriasis, contact dermatitis, and skin pruritus.
20. The method for preparing the pad for treating skin diseases according to claim 15, characterized in that the skin disease is a disease showing vascular exudation of plasma proteins.
21. The method for preparing the pad for treating skin diseases according to claim 16, characterized in that the skin disease is a disease showing vascular exudation of plasma proteins.
Description
DESCRIPTION OF DRAWINGS
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MODE FOR INVENTION
[0066] Hereinafter, the present invention will now be described in more detail by way of non-limiting examples. Provided that, the following examples are intended to illustrate the present invention and the scope of the present invention is not to be construed as being limited by the following examples.
Example 1: Preparation of the Pad of the Present Invention
[0067] The pad of the present invention was prepared by putting 2% (w/v) agar in a 50% NaCl solution (about 70 mM) of saline, autoclaving (121 C., 151b/cm.sup.2, 15 min) and then pouring it into a mold to be a thickness of 2 mm, when cooled at 60-70 C. When the agar solution was maintained in the liquid phase (about 55-70 C.) before hardening, fibers (paper, thin cotton, fiber, etc.) were placed on the surface and cured together with the agar gel so as to be united. After the agar gel was completely hardened, the agar film, which occasionally climbed over the fibrous layer and hardened to form, was scraped off with a flat, sharp tool to remove it clearly.
[0068] In preparing the pads containing the various compositions described in Table 1 in addition to the basic pads of the present invention, when the gel is in the liquid phase before hardening it (55-70 C.), the components to be required (for example, organic acid, lecithin, and the like, as described in Table 1) were added, mixed well and then hardened by pouring them into a mold. Upon mixing the composition required for the gel, care was taken to prevent air bubbles from forming the inside of the gel.
Experimental Example 1: Measurement of Epidermal Temperature and Epidermis Cooling Effect of the Pad
[0069] The temperature change of epidermis was monitored using a wireless temperature sensor (SL52T data logger, Signatrol, UK). In order to confirm the effect of the pad on lowering the epidermal temperature, the temperature change was determined for each of cases that temperature sensor was placed on the skin inside the normal forearm, and then covered with two layers of gauze, and that the temperature sensor was placed on the skin, and then the pad (68 cm, 2 mm thickness, 50% NaCl concentration) was placed on the it. In addition, in order to confirm the continuous effect of pad on skin cooling, the temperature changes were compared using nonwoven fabrics (68 cm) for a mask pack, socked with a salt concentration solution of 50% physiological saline. Experiments were carried out at room temperature, and the mean room temperature at the time of the experiment was 251 C. and the mean relative humidity was 30%. Each of gauze, pad, and nonwoven fabric soaked in saline, including a temperature sensor, was fixed on the skin using SurgeNet.
[0070] As a result of the experiment, the epidermal temperature of the normal person was 32.50.5 C. (n=4), and the pad of the present invention was able to lower the epidermal temperature by about 5.80.3 C. On the contrary, the wet nonwoven fabric was able to temporarily lower the epidermal temperature, but was found to be non-persistent (
[0071] The temperatures of the normal and affected areas of atopic patients were measured in the same manner as above and compared with the skin temperature of the normal person.
[0072] The average temperature of the normal parts of the atopic dermatitis patients was 34.050.4 C. (n=2) and the average temperature of affected parts showing inflammation was 34.10.5 C. The epidermal temperature of the affected area with the pad was kept low by an average of 6.250.2 C.
[0073] From the above results, the skin temperature of the patient with atopic skin disease was about 1.5 C. higher than that of the normal person, and the temperature of the affected part was finely higher than the other normal parts of the patient. It can be inferred that the atopic skin disease is associated with vasodilatory factors.
[0074] When applying the pad of the present invention, it was observed that the skin temperature was lowered at the affected area of the atopic patient as compared with the normal skin. This reason can be explained by the phenomenon occurred by that the epidermal temperature is relatively high and thus the evaporation of water on the pad surface is increase.
Experimental Example 2: The Duration for Lowering the Epidermal Temperature by the Pad of the Present Invention
[0075] A pad having 2 mm thickness was closely attached to the surface of a heating block flat plate set at 32 C. (11.36.6 cm custom-made, Dry Bath, Thermo Scientific, USA), and the weight of the pads was measured at constant intervals to calculate the amount of moisture evaporated. The gel of the pad was prepared so as to contain 50% NaCl concentration of physiological saline, and based on this, the time point at which 50% of the moisture of the pad is evaporated to be higher to the physiological salt concentration is set as the epidermis application time. As a result of the experiment, the application time of the pad was measured to be about 4 hours and 30 minutes. It is expected that the amount of moisture evaporation will be further increased because the heat generation in the affected area of the patient is slightly higher than that of the normal skin. That is, when using pads having the same thickness, it is possible to apply a relatively short application time or to extend the application time by increasing the thickness of the pad.
Experimental Example 3: Adjustment of the Pad of the Present Invention for Lowering the Epidermal Temperature
[0076] When the pad is applied to the epidermis, the effect is shown that the epidermal temperature of the applied area is lowered by about 6 C. under the environmental conditions fixed given in the laboratory. Occasionally, a user may feel cold due to a rarely lowered temperature difference. To alleviate this discomfort, it is necessary to control the degree of lowering of the epidermal temperature by adjusting the moisture evaporation amount of the pad. It is possible to control the lowering of the epidermal temperature by attaching a polyvinyl film perforated at constant intervals to the surface of the pad and controlling the moisture evaporation. When moisture evaporation was measured at the surface of the hot plate set at 32 C., the evaporation rate of moisture was reduced by 64% when the pads were covered with the vinyl film perforated in the area of 30%, and when the pads were covered with the vinyl film perforated in the area of 15%, the moisture evaporation was reduced by 52% (
[0077] Such a temperature control method can be selectively used as a method for reducing the inconvenience caused by the patient's cold. In addition, it can be used as a method for delaying the evaporation of moisture and extending the application time of the epidermis of the pad.
[0078] By controlling the moisture evaporation of the pad surface, the effect of lowering the skin temperature of the pad can be controlled. The pad surface was covered with a 15% and 30% perforated vinyl film, respectively, to control the moisture evaporation. The moisture evaporation was reduced by 52% when 15% of the surface of the pad was exposed, and moisture evaporation was reduced by 64% when 30% of the pad surface was exposed. The effect of lowering the epidermal temperature was lowered to about 50% and 70%, respectively, as compared with the pad of which entire surface was exposed.
Experimental Example 4: Pumping Action of the Pad of the Present Invention by Moisture Evaporation
[0079] When moisture evaporates from the surface of the pad, a phenomenon occurs in which the materials are rapidly moved from the bottom surface of the pad toward the top surface. Pumping action is an important mechanism used to remove plasma proteins, various ions and organic materials accumulated in atopic skin diseases and various exudative skin diseases from the epidermis. In this experiment, the following experiment was designed to demonstrate the pumping action of the pad.
[0080] A Finn Chamber (diameter 11 mm) for Filter Paper Disc was placed on a heating block set at 32 C. and fully filled with 0.1% (w/v) bromophenol blue (BPB, molecular weight 669.9) solution. After covering the chamber with a wrap, a hole was made with a needle having a constant thickness in the center of the chamber, and the pad was brought into contact with it immediately above.
[0081] The movement of the BPB staining reagent was observed while the top surface of the pad was normally exposed to air and the upper surface of the pad was covered with a wrap (
[0082] As moisture evaporates from the surface of the pad, a force acts to pull the material up from the bottom of the pad to the upper surface of the pad. This pumping action of the pad can be applied to remove plasma proteins accumulated from the epidermis, various ions derived from plasma and other organic substances. From this result, it is important to expose the upper surface of the pad to the outside to keep the moisture evaporation smoothly, when the pad is applied to the skin.
Experimental Example 5: The Pumping Function of the Protein of the Present Invention in the Affected Area of the Patient with Atopy
[0083] After the pad was applied to the affected area of the patient with atopic dermatitis for 3.5 hours, it was collected to identify the proteins transferred into the gel of the pad. The pad which was applied to the patient for 3 hours and 30 minutes and collected were diced with a razor and then incubated in a 4 SDS-PAGE sample buffer for 1 hour. The crushed gel fragments and SDS-sample buffer were centrifuged (at 500 g for 30 min) using 0.45 micrometer, Spin-X centrifuge tubes (Coster, Corning). The collected samples were developed on a 10% (w/v) SDS-PAGE gel. The developed proteins were visualized by Coomassie Brilliant Blue-R250 staining method. As a result of the experiment, it was confirmed that plasma albumin (67 kDa) and small proteins were migrated into the pad. It shows the result that pads have an effect of lowering the epidermal temperature and at the same time have the effect of eliminating the proteins accumulated in the skin tissue by exuding from the blood vessels, thereby helping to improve the symptom of atopic dermatitis and the similar exudative skin diseases (
Experimental Example 6: Major Components of the Pad and Test Verifying the Effect for Improving the Symptoms
[0084] The pads aimed by the present invention have effects of shrinking blood vessels around the affected area by constantly lowering the epidermal temperature by only a unique basic structure and removing exuded proteins accumulated on the epidermis to improve symptoms. However, if the exuded proteins are more effectively removed and simultaneously the itchy sensation is reduced, the effect for improving the symptoms can be made more rapidly, and thus, it has been attempted to improve the symptom improvement effect by adding organic acid and lecithin to the composition of the pad. The organic acids used in the present invention were used for the purpose of hindering the hydrophobic binding and the ionic bonding of the organic acid, and lecithin (total phospholipids extracted from animals or plants) was used as a material with a detergent-like property.
[0085] As the used organic acids, acetic acid and butyric acid were used by adding them to the pads in the same concentration, based on propionic acid, and they were compared for the effects improving symptoms.
[0086] The lecithin used in this experiment was palm lecithin and lecithin extracted from pig lung tissue, respectively. Palm lecithin was extracted from crude palm oil by the method (Pardun H. (1988), Pflanzenlecithine. Gewinnung, Eigenschaften, Verarbeitung and Anwendung pflanzlicher Phosphatidpraparate. Ziolkowsky, Augsburg ISBN 3-87846-128-3). Lecithin extracted from lung tissue of pigs was extracted and purified by the method described by Moon, et al. (Moon J. S., Jeon B. S., Yoon B. I., Choi S. H. and Lim C. J. (2012) Mol. Biol. Rep. 39:4237-4247).
[0087] In order to investigate the efficacy and effect of the pad of the basic form and the pad containing various compositions of the present invention, the experiment candidates were selected from patients suffering from atopic dermatitis, atopic eczema, and contact dermatitis. Participants were patients diagnosed with each disease at local or general hospitals. Patients were told about the safety of the ingredients in the pads, but they were made not to notice as to which ingredients of pads were applied. The application time of each pad was 3 hours and 30 minutes, and after the pad was removed from the affected area, a photograph was taken after the lapse of 20 minutes to compare the degree of improvement of the skin.
[0088] In order to assess efficacy and effect, two items were made to be evaluated by the patients themselves. 1. How much did the itchy sensation decrease, 2. What is the degree to which the skin is improved by the patient; With respect to these two items, it was evaluated as 3 points with respect to that the state became worse and +3 points with respect to that the effect is better, based on 0 point with respect to that no effect is improved. In addition to the two items that the patients themselves evaluated, three researchers compared the photographs of patients before and after the treatment of the patients, and then, the inflammation reduction effect was evaluated as a score and the average value was reflected in the efficacy and effect evaluation.
[0089] Table 1 shows the pads formed to observe the symptom improvement effect.
TABLE-US-00001 TABLE 1 Pad Name Composition of the components P-FB Non-woven fabric (soaked with 50% physiological saline concentration) P-B Pad (Basic form) P-BP Pad + 10 microM propionic acid/propionate sodium salt (p5.8) P-BA Pad + 10 microM acetic acid/acetate sodium salt (pH 5.8) P-BB Pad + 10 microM butyric acid/butyrate sodium salt (pH 5.8) P-BPLL Pad + 10 microM propionic acid/propionate sodium salt (p5.8) + lecithin isolated from pig lung tissue P-BPPL Pad + 10 microM propionic acid/propionate(p5.8) + lecithin isolated from Palm
[0090] Table 1 shows the types of pads used for the efficacy and effect test.
Results Obtained after Applying Atopic Dermatitis
TABLE-US-00002 TABLE 2 Reduction Improvement of itchy for symptoms Improvement of sensation of the skin dermatitis Numbers Kinds of (Self- (Self- (Assessment by of the pad assessment) assessment) photograph result) patients P-F Not Not 0.5 2 assessable assessable P-B 1.5 1.5 0.58 3 P-BP 1.7 1.7 0.92 13 P-BA 1.0 1.0 0.5 2 P-BB 1.6 1.6 0.87 2 P-BPLL 1.7 1.7 1.15 5 P-BPPL 2.0 2.0 1.14 6
[0091] Table 2 shows the results of the efficacy and effect assessment of Pad when applied to patients with atopic dermatitis.
[0092] In order to investigate the effect of each of the animal and vegetable lecithin added to the pad of the present invention on efficacy, it was applied to patients having atopic eczema. Evaluation was performed in the same manner as patients with atopic dermatitis. The results are as follows (Table 3).
TABLE-US-00003 TABLE 3 Reduction Improvement of itchy for symptoms Improvement of sensation of the skin dermatitis Numbers Kinds of (Self- (Self- (Assessment by of the pad assessment) assessment) photo result) patients P-BP 2.3 1.8 0.75 4 P-BPLL 2.5 1.5 0.8 2 p-BPPL 2.0 1.5 0.17 3
[0093] Table 3 shows the results of the efficacy and effect evaluation when the pad was applied to patients with atopic eczema.
[0094] In order to investigate the effect of added additional lecithin in addition to the organic acids added to the basic pad, the effects were evaluated by applying it to patients with contact dermatitis. The evaluation method is the same as that applied to patients with atopic dermatitis and atopic eczema, as mentioned above.
TABLE-US-00004 TABLE 4 Reduction Improvement of itchy for symptoms Improvement of sensation of the skin dermatitis Numbers Kinds of (Self- (Self- (Assessment by of the pad assessment) assessment) photo result) patients P-BP 1.0 1.5 0.5 2 P-BPLL 1.5 1 0.9 2 p-BPPL 1.0 1.5 0.8 2
[0095] Table 4 shows the results of the efficacy evaluation when pad was applied to patients with contact dermatitis.
[0096] When the pad with various compositions were applied to patients with atopic dermatitis, eczema, and contact dermatitis, the pads showed symptomatic improvement to the degree that can be confirmed by naked eyes even by one application (3 hours 30 minutes) (Examples of symptom improvements for each disease:
Application of the Pad of the Present Invention (Psoriasis)
[0097] The improvement effect was confirmed by applying the P-BPPL Pad described above to the epidermis of the patient with psoriasis. After applying the relevant pad for 4 hours, the photographs were taken to confirm the improvement of symptoms. It was clearly observed that the background color of the affected area was decreased, and the texture of the keratin was changed. (
Application of the Pad of the Present Invention (Mosquito Bite)
[0098] When the mosquito bites, itchy sensation and local warmth are produced together with vasodilatation. Since the pad of the present invention has functions for vasoconstriction, cooling the affected areas, and reduction of itchy sensation, the effect is observed by applying it to the skin bitten by the mosquito. There are three observation opportunities in total. The pad used at this time was pad containing propionic acid in concentration of 20 times or more (20 micro-M propionic acid/propionate, pH 5.8) than that of Pad P-BP (containing 1 micro-M propionic acid/propionate) described above. After application of the pad, it was observed that the time taken until itchy sensation was disappeared was 15 minutes on average, and the time taken until a wheal generated by the mosquito bite was gone down was about 45 minutes (
Results of Other Observations
[0099] When the concentration of organic acids is increased, the time until the reduction of the itchy sensation felt by patients is accelerated, however, in some cases, the condition of the affected area may be deteriorated. In particular, when the pad containing propionic acid having the concentration of 20 micro-M was applied of the present invention for 1 hour, there was a case that the affected area was swollen and oozing became more severe. This is presumed to be the result that propionic acid was excessively transferred to the skin under the condition that the skin barrier of the patient with atopic dermatitis was damaged.
[0100] The calcium ion concentration required for stabilization of the epidermal structure is nM (nano-M) level, but there is a possibility that the highly transferred propionic acid may have been interfered with the intrinsic function of calcium. On the other hand, in the skin of normal person, it was applied such that the concentration of propionic acid in the pad was increased to 60 micro-M concentration, but no negative effect was observed. On the other hand, patients suffering from atopic dermatitis for a long time and thus having the thickened keratin (lichenification) did not show any skin abnormal reactions even though the pad containing 40 micro-M of propionic acid was used.
[0101] 1 mg/ml lecithin was used in the efficacy and effect test using lecithin, but no abnormal reaction was observed even though pad containing 80 mg/ml phospholipid was applied to an atopic patient with the damaged keratin. It is assumed to be the result due to that since the phospholipid molecules contained in lecithin has larger molecular weight than that of organic acid molecules, the amounts of phospholipid molecules delivered to the inside of the skin are relatively small and most of the molecules are moved to the upper surface of the gel by pumping action of the pad.
Application as Cosmetics
[0102] In connection with the pad of the present invention, in the detailed description of the present invention, it has demonstrated the adsorption of a dyeing reagent with a molecular weight of 700 Da and shown the adsorption of proteins in the treatment of atopic patients. That is, it can be inferred that such adsorption function of the pad can exhibit a cleansing effect removing the wastes of the skin by using the pad as cosmetics.
[0103]
[0104] As can be seen in the photograph of