Applications of mussel adhesive protein product in treatment and prevention of diseases related to melanin

Abstract

Disclosed are applications of a mussel adhesive protein or preparations thereof in treatment and prevention of diseases related to melanin. Specifically disclosed are applications of a mussel adhesive protein or preparations thereof in treatment and prevention of pigmentations such as chloasma, freckles, melanosis, applications in skin cancers represented by melanoma, and applications in treatment of pigmentation possibly caused by skin diseases or drugs.

Claims

1. A method for treating melanin pigmentation, the method comprising administering to an individual in need thereof an effective amount of a composition comprising a mussel adhesive protein (MAP), wherein the MAP comprises M. edulis foot protein 1 (mefp-1), and wherein said administering treats melanin pigmentation.

2. The method according to claim 1, wherein the MAP is present in the composition at a concentration of 0.1 to 15.0 mg/ml.

3. The method according to claim 1, wherein the composition is a liquid formulation, a gel formulation, a lotion, a paste, a foam formulation, or in the form of a therapy patch.

4. The method according to claim 1, wherein the composition has a pH in the range of 1.0 to 7.0.

5. The method according to claim 4, wherein the composition has a pH in the range of 3.0 to 6.5.

6. The method according to claim 1, wherein the melanin pigmentation is selected from the group consisting of chloasma, freckles, melanosis, chromatosis and skin cancers.

7. The method according to claim 6, wherein the melanin pigmentation comprises melanoma or chromatosis caused by exposure to the sun or a skin disease.

8. The method according to claim 1, wherein the melanin pigmentation is melanin pigmentation after burns.

9. The method according to claim 1, wherein the composition is suitable for external skin application.

10. The method according to claim 1, wherein the composition is a medicine, a cosmetic preparation, a disinfecting product, a healthcare product, a food or a household chemical.

11. The method according to claim 1, further comprising administering an enzyme to the individual.

12. The method according to claim 11, further comprising creating a micro-wound surface and administering the MAP to the micro-wound surface, wherein the MAP is administered directly or after creating the micro-wound surface.

13. The method according to claim 12, wherein said creating the micro-wound surface is carried out using a micro-needle, a rolling needle, or a laser.

14. The method according to claim 11, wherein the enzyme is selected from the group consisting of trypsin, a collagenase, a caseinase, chymotrypsin, a carboxypeptidase, a ceratinase, an enterokinase, and rennet.

15. The method according to claim 11, wherein said administering the composition and said administering the enzyme comprises: (a) spraying a composition comprising the enzyme onto the skin surface to decompose the corneous layer on the skin surface, repeating said spraying the composition comprising the enzyme onto the skin surface, and then spraying the composition comprising the MAP onto the skin surface; or (b) spraying the composition comprising the MAP onto the skin surface, and then spraying a composition comprising the enzyme onto the skin surface; or (c) mixing the composition comprising the MAP with a composition comprising the enzyme and then spraying the mixture onto the skin surface; or (d) spraying a composition comprising the enzyme onto the skin surface, and then spraying the composition comprising the MAP onto the skin surface.

16. The method according to claim 11, wherein the composition comprising the MAP and the enzyme are provided in different packages.

17. The method according to claim 11, wherein the MAP is provided in the form of a mixture of hydrolyzed MAP peptides or the form of a single hydrolyzed MAP peptide.

18. The method according to claim 11, wherein the molar ratio of MAP to the enzyme is in the range of 0.1:1 to 100:1.

19. The method according to claim 18, wherein the molar ratio is in the range of 1:1 to 50:1.

Description

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

(1) Embodiments of the present invention comprise:

(2) 1. Use of MAP in treating and preventing melanin pigmentation.

(3) 2. The use of MAP according to Embodiment 1, wherein the MAP may be one or a mixture of several selected from the group consisting of subtypes mefp-1, mefp-2, mefp-3, mefp-4, mefp-5, mefp-6, the collagens pre-COL-P, pre-COL-D, pre-COL-NG, and the mussel feet matrix proteins PTMP and DTMP.

(4) 3. The use of MAP according to Embodiment 1, wherein the MAP concentration may be 0.1-15.0 mg/mL.

(5) 4. The use of MAP according to Embodiment 1, wherein the MAP may be a liquid formulation, a gel formulation, a lotion, a paste, a therapy patch, or a foam formulation in use.

(6) 5. The use of MAP according to Embodiment 1, wherein MAP in the final product may be in a range of pH 1.0-7.0, and in particular, in a range of pH 3.0-6.5.

(7) 6. The use of MAP according to any one of Embodiments 1-5, wherein the melanin pigmentation may be chloasma, freckles, melanosis and other chromatosis, skin cancers with melanoma as a representative, and chromatosis that is caused by exposure to the sun or skin diseases like acne.

(8) 7. The use of MAP according to Embodiment 1, wherein the MAP may be used independently or combined with an enzyme in use.

(9) 8. The use of MAP according to Embodiment 7, wherein the MAP may be used directly or after a micro wound surface is created first.

(10) 9. The use of MAP according to Embodiment 8, wherein the methods to create a micro wound surface may include: micro-needle (which can be made of silicon, silicon dioxide, cellulose, etc.), rolling needle (which can be made of stainless steel, titanium, polytetrafluoroethylene, etc.), laser (e.g. fractional laser).

(11) 10. The use of MAP according to Embodiment 7, wherein the enzyme may be: (1) trypsin from various sources, for example, trypsin extracted from cod pancreas, bull pancreas, pig pancreas, and euphausiid shrimp; (2) collagenases from various sources; (3) caseinase from various sources; (4) chymotrypsin from various sources; (5) carboxypeptidase from various sources; (6) ceratinase from various sources; (7) enterokinase from various sources; (8) rennet from various sources, etc.

(12) 11. The use of MAP according to Embodiment 7, wherein the manner of use of a combination of MAP and an enzyme may comprise: (1) spray the enzyme first to decompose the corneous layer on the skin surface, then spray the enzyme again, and immediately spray MAP for them to work together for a period of time; (2) spray MAP first, and then spray the enzyme for them to work together for a period of time; (3) mix MAP with the enzyme for a period of time, and then spray it for use; (4) spray the enzyme first, and then spray MAP for them to work together for a period of time.

(13) 12. The use of MAP according to Embodiment 7, wherein MAP and the enzyme may be in different packagings.

(14) 13. The use of MAP according to Embodiment 7, wherein the use of a combination of MAP and an enzyme may be a use in the form of a mixture of hydrolyzed MAP peptides.

(15) 14. The use of MAP according to Embodiment 7, wherein the use of a combination of MAP and an enzyme may be a use in the form of a single hydrolyzed MAP peptide.

(16) 15. The use of MAP according to Embodiment 7, wherein the molar ratio of MAP to an enzyme may be in a range of 0.1:1-100:1, preferably in a range of 1:1-50:1.

(17) 16. Use of MAP as an active ingredient in a composition for treatment and prevention of melanin pigmentation, wherein the composition is a liquid formulation, a gel formulation, a lotion, a paste, a therapy patch, or a foam formulation in use.

(18) 17. The use of MAP according to Embodiment 16, wherein the composition is a composition for external application on the skin.

(19) 18. Use of MAP as an active ingredient in a drug for treatment of melanin.

(20) 19. Use of MAP as an active ingredient in a medical device for treatment of melanin.

(21) 20. Use of MAP as an active ingredient in a cosmetic for treatment of melanin.

(22) 21. Use of MAP as an active ingredient in a disinfecting product for treatment of melanin.

(23) 22. Use of MAP as an active ingredient in a healthcare product or food for treatment of melanin.

(24) 23. Use of MAP as an active ingredient in a household chemical for treatment of melanin.

(25) 24. The use of MAP according to any one of Embodiments 16-23, wherein MAP is combined with an enzyme in use.

(26) 25. A drug for treatment of melanin pigmentation, comprising MAP and a pharmaceutically acceptable carrier, wherein the MAP concentration is 0.1-15.0 mg/mL.

(27) 26. A medical device for treatment of melanin pigmentation, comprising MAP and a carrier acceptable in the field of medical devices, wherein the MAP concentration is 0.1-15.0 mg/mL.

(28) 27. A cosmetic for treatment of melanin pigmentation, comprising MAP and a carrier acceptable in the field of cosmetics, wherein the MAP concentration is 0.1-15.0 mg/mL.

(29) 28. A disinfecting product for treatment of melanin pigmentation, comprising MAP and a carrier acceptable in the field of disinfecting products, wherein the MAP concentration is 0.1-15.0 mg/mL.

(30) 29. A healthcare product or food for treatment of melanin pigmentation, comprising MAP and a carrier acceptable in the field of healthcare products or foods, wherein the MAP concentration is 0.1-15.0 mg/mL.

(31) 30. A household chemical for treatment of melanin pigmentation, comprising MAP and a carrier acceptable in the field of household chemicals, wherein the MAP concentration is 0.1-15.0 mg/mL.

(32) 31. The drug according to any one of Embodiments 25-30, further comprising an enzyme.

(33) The present invention will be further described below with reference to specific embodiments. It should be noted that, when a drug, medical device, cosmetic, disinfecting product, healthcare product or food, or household chemical formed from MAP or various formulations of MAP according to the present invention is applied on a subject, it can be used for the indications described above and exhibits the functions described above. All formulations within the scope of the present invention have been tested, and only a small portion thereof are described below in the embodiments for the purpose of description; however, they shall not be construed as limitations to the present invention.

(34) Unless otherwise specifically described, all reagents used in the present invention are commercially available on the market.

Example 1

Use of MAP Gel Cosmetic in Treatment of Chloasma

(35) Mix an MAP solution with polyvinyl alcohol, hydroxypropyl cellulose, and glycerin at a mass ratio of 2:2:1:2 to obtain an MAP gel cosmetic with an MAP concentration of 3 mg/g.

(36) Gather 10 patients with chloasma. It is required that the selected patients have the chin affected and the color of the patches is dark brown. They are diagnosed by dermatologists and then join the groups for test. Apply the above MAP gel cosmetic at the affected part once per day, and evenly apply the gel on the surface of the affected part each time. Measure the pigment value of the affected part using a pigment measurement instrument every 10 days. For the 10 patients, the pigment value of the affected part decreases by 9% at 50 days after application of the MAP gel cosmetic (see Table 1), proving that long-term use of the MAP product can reduce pigmentation at the position of chloasma.

(37) TABLE-US-00001 TABLE 1 Average pigment value of the affected part at  308 ± 10.7 Day 0 Average pigment value after 10 days of use 303.4 ± 9.9  Average pigment value after 20 days of use 299.2 ± 9.5  Average pigment value after 30 days of use 293.6 ± 8.2  Average pigment value after 40 days of use 286.6 ± 5.8  Average pigment value after 50 days of use 280.6 ± 6.8 

Example 2

Use of MAP Household Chemical Lotion in Treatment of Chloasma

(38) Mix an MAP solution with propanediol and glycerin at a mass ratio of 2:2:1 to obtain an MAP household chemical lotion with an MAP concentration of 1.5 mg/g.

(39) Gather 10 patients with chloasma. It is required that the selected patients have the chin affected and the color of the patches is dark brown. They are diagnosed by dermatologists and then join the groups for test. Apply the above MAP household chemical lotion at the affected part two times per day, and evenly apply the household chemical lotion on the surface of the affected part each time. Measure the pigment value of the affected part using a pigment measurement instrument every 10 days. For the 10 patients, the pigment value of the affected part decreases by 7.3% at 50 days after application of the MAP household chemical lotion (see Table 2), proving that long-term use of the MAP product can reduce pigmentation at the position of chloasma.

(40) TABLE-US-00002 TABLE 2 Average pigment value of the affected part 316.0 ± 13.6  at Day 0 Average pigment value after 10 days of use 313.8 ± 9.3  Average pigment value after 20 days of use 309.4 ± 7.8  Average pigment value after 30 days of use 302.3 ± 7.2  Average pigment value after 40 days of use 298.6 ± 6.9  Average pigment value after 50 days of use 293.9 ± 8.2 

Example 3

Use of MAP Liquid Medical Device in Treatment of Chloasma

(41) Take 1 mL of an MAP solution with concentration at 20.0 mg/mL, add 9 mL of 0.1% citric acid solution, and prepare an aqueous solution with the MAP concentration at 2.0 mg/mL. Take 1.0 mg cod enzyme, and add 1.0 mL deionized water to prepare a solution with a concentration of 1.0 mg/mL.

(42) Gather 30 patients with chloasma diagnosed by dermatologists for test. The patients have brown patches at the affected part.

(43) The selected patients are randomly divided into three groups. For the first group marked as Group A, apply a commercially available spot-removing liquid at the affected part. For the second group marked as Group B, spray the above MAP liquid medical device at the affected part; for the third group marked as Group C, spray a composition of the MAP liquid medical device and an enzyme at the affected part, and in use, spray MAP first, and then spray the enzyme formulation. There are three drug administrations per day for all the three groups, and the dose is sufficient for the drugs to be evenly applied at the affected part. Prior to use, measure the melanin value of the affected part and the melanin value of areas surrounding the affected part and having no colored patches. Measure the melanin value of the affected part every 10 to 30 days, and calculate the rate of melanin change at the affected part (see Table 3 for results).

(44) The rate of melanin change is calculated using the following equation:
(melanin value before use−melanin value after use)/(melanin value before use−melanin value of a normal position)×100%

(45) TABLE-US-00003 TABLE 3 Use Rate of melanin Rate of melanin Rate of melanin time change change change for (d) for Group A (%) for Group B (%) Group C (%) 10 0.6 ± 0.2 2.6 ± 0.4  8.3 ± 1.9 30 1.2 ± 0.3 5.8 ± 1.2 16.9 ± 2.7 60 4.3 ± 0.8 9.6 ± 1.8 20.6 ± 3.1 90 5.2 ± 1.6 13.7 ± 2.5  28.2 ± 2.8

(46) The results show that compared with the commercially available spot-removing product, after 90 days of using the MAP liquid medical device, the rate of pigment value change at the affected part is more than one times, and the spot-removing effect is better than that of the commercially available product. After 90 days of using a combination of the MAP liquid medical device and an enzyme, the rate of pigment value change at the affected part reaches up to 28.2%, which achieves a significant effect on improving chloasma at the affected part. Moreover, compared with the use of the MAP product alone, the combined use of the MAP product and an enzyme increases the rate of pigment value change at the affected part by one time, which is more favorable for treatment of chloasma.

Example 4

Use of MAP Hydrogel Cosmetic in Treatment of Chloasma

(47) Take 10 g sodium carboxymethyl cellulose, add 20 mL deionized water, place in a bath at 90□ for 30 min. until complete dissolution to obtain a gel matrix, separately take 2.5 mL of an MAP solution with concentration at 10.0 mg/mL, add it into the gel matrix while stirring, and mix homogeneously to form an MAP hydrogel cosmetic, wherein the MAP concentration is 1.1 mg/mL. Take 1.0 mg cod enzyme, and add 1.0 mL deionized water to prepare a solution with a concentration of 1.0 mg/mL.

(48) Gather 20 patients with chloasma diagnosed by dermatologists for test. The patients have brown patches at the affected part.

(49) For the selected patients, spray the above MAP hydrogel cosmetic at the affected part, and in use, spray the MAP hydrogel cosmetic first, and then spray the enzyme formulation, three times per day. Prior to use, measure the melanin value of the affected part and the melanin value of areas surrounding the affected part and having no colored patches. Measure the melanin value of the affected part every 10 to 30 days, and calculate the rate of melanin change at the affected part (see Table 4 for results).

(50) The rate of melanin change is calculated using the following equation:
(melanin value before use−melanin value after use)/(melanin value before use−melanin value of a normal position)×100%

(51) TABLE-US-00004 TABLE 4 Use time (d) Rate of melanin change (%) 10  9.6 ± 1.6 30 18.2 ± 1.9 60 29.6 ± 2.7 90 38.4 ± 1.8

(52) The results show that After 10 days of using the MAP hydrogel cosmetic and the enzyme, the pigment value at the affected part has begun to decrease, and along with the extended use time, the rate of the pigment value change at the affected part increases. As of 90 days of use, the pigment change at the affected part is more than 1/3. The MAP product according to the present invention can mitigate pigmentation at the position of chloasma, and can be used for treatment of chloasma.

Example 5

Use of MAP Liquid Drug in Treatment of Freckles

(53) Take 1 mL of an MAP solution with concentration at 10.0 mg/mL, add 9 mL of 0.1% citric acid solution, and prepare a liquid drug with the MAP concentration at 1.0 mg/mL. Take 1.0 mg trypsin, and add 1.0 mL deionized water to prepare a solution with a concentration of 1.0 mg/mL.

(54) Gather 20 patients with freckles diagnosed by dermatologists for test. The patients have brown patches at the affected part.

(55) For the selected patients, spray the above MAP liquid drug at the affected part, and in use, spray the MAP liquid drug first, and then spray the enzyme formulation, three times per day. Prior to use, measure the melanin value of the affected part and the melanin value of areas surrounding the affected part and having no colored patches. Measure the melanin value of the affected part every 10 to 30 days, and calculate the rate of melanin change at the affected part (see Table 5 for results).

(56) The rate of melanin change is calculated using the following equation:
(melanin value before use−melanin value after use)/(melanin value before use−melanin value of a normal position)×100%

(57) TABLE-US-00005 TABLE 5 Use time (d) Rate of melanin change (%) 10  6.4 ± 1.4 30 21.6 ± 2.8 60 28.7 ± 2.9 90 35.2 ± 3.6

(58) The results show that After 10 days of using the MAP liquid drug and the enzyme, the pigment value at the affected part has begun to decrease, and along with the extended use time, the rate of the melanin change at the affected part increases. As of 90 days of use, the pigment change at the affected part reaches up to 35.2%, proving that the MAP product according to the present invention can mitigate pigmentation for patients with freckles, and can be used for treatment of freckles.

Example 6

Use of MAP Household Chemical Lotion in Treatment of Freckles

(59) Mix propanediol and propanetriol at a ratio of 1:1 to obtain a lotion matrix, separately take 2.5 mL of an MAP solution with concentration at 10.0 mg/mL, add it into the lotion matrix while stirring, and mix homogeneously to form an MAP household chemical lotion, wherein the MAP concentration is 3.0 mg/mL.

(60) Gather 30 patients with freckles diagnosed by dermatologists for test. The patients have brown patches at the affected part.

(61) The selected patients are randomly divided into three groups. For the first group marked as Group A, a commercially available spot-removing lotion is applied. For the second group marked as Group B, directly apply the above MAP household chemical lotion at the affected part; for the third group marked as Group C, first use micro-needle to create a micro-wound surface at the affected part, and then apply the MAP household chemical lotion at the affected part. There are three drug administrations per day for all three groups, and the dose is sufficient for the drug to be evenly applied at the affected part. Prior to use, measure the melanin value of the affected part and the melanin value of areas surrounding the affected part and having no colored patches. After using MAP, measure the melanin value of the affected part every 10 to 30 days, and calculate the rate of melanin change at the affected part (see Table 6 for results).

(62) The rate of melanin change is calculated using the following equation:
(melanin value before use−melanin value after use)/(melanin value before use−melanin value of a normal position)×100%

(63) TABLE-US-00006 TABLE 6 Rate of melanin Rate of melanin Rate of melanin Use time change change change (d) for Group A (%) for Group B (%) for Group C (%) 10 0.5 ± 0.3  3.9 ± 0.9 11.3 ± 2.6 30 1.1 ± 0.4  7.2 ± 1.6 28.5 ± 2.9 60 3.9 ± 0.7 11.6 ± 1.7 34.8 ± 3.8 90 5.0 ± 1.2 16.7 ± 2.4 42.6 ± 3.1

(64) The results show that compared with the commercially available product, after 90 days of using the MAP household chemical lotion, the rate of melanin change is increased three times. After 90 days of using a combination of the MAP household chemical lotion and an enzyme, the rate of pigment value change at the affected part reaches up to 42.6%, which achieves a significant effect on improving freckle pigmentation at the affected part. Moreover, compared with the use of the MAP product alone, the combined use of the MAP product and an enzyme increases the rate of pigment value change at the affected part 2.5 times, which is more favorable for treatment of freckles.

Example 7

Use of MAP Lotion Cosmetic in Treatment of Melanosis

(65) Mix MAP freeze-dried powder with gelatin, isinglass, and glycerin at a ratio of 3:1:1:0.5 to form an MAP lotion cosmetic, wherein the MAP concentration is 5.5 mg/mL.

(66) Gather 12 patients with melanosis diagnosed by dermatologists. The patients use the above MAP lotion cosmetic twice a day at an amount capable of completely covering the testing area for 90 days in a row.

(67) Measure the pigment situation of the affected part using a pigment measurement instrument. After 20 days of continuous use, the average pigment value of the affected part begins to decrease to around 96% of the initial value. At 90 days, the pigment value of the affected part decreases to 82.6% of the initial value (see Table 7), proving that the use of the MAP product according to the present invention can decrease pigmentation in melanosis.

(68) TABLE-US-00007 TABLE 7 Average pigment value of the affected part 328.0 ± 23.7 at Day 0 Average pigment value after 20 days of use 317.7 ± 19.5 Average pigment value after 40 days of use 303.4 ± 15.8 Average pigment value after 60 days of use 292.6 ± 16.9 Average pigment value after 80 days of use 285.9 ± 18.1 Average pigment value after 90 days of use 271.2 ± 28.8

Example 8

Use of MAP Gel Healthcare Product in Treatment of Melanosis

(69) Mix an MAP solution with gelatin and glycerin at a ratio of 1:1:1 to form an MAP gel healthcare product, wherein the MAP concentration is 10.0 mg/mL.

(70) Gather 12 patients with melanosis diagnosed by dermatologists. The patients use the above MAP gel healthcare product twice a day at a dose capable of completely covering the testing area for 90 days in a row.

(71) Measure the pigment situation of the affected part using a pigment measurement instrument. After 20 days of continuous use, the average pigment value of the affected part begins to decrease to 96% of the initial value. At 90 days, the pigment value of the affected part decreases to 80% of the initial value (see Table 8), proving that the use of the MAP product according to the present invention can decrease pigmentation in melanosis.

(72) TABLE-US-00008 TABLE 8 Average pigment value of the affected part 353.3 ± 43.1 at Day 0 Average pigment value after 20 days of use 341.7 ± 36.4 Average pigment value after 40 days of use 316.6 ± 25.6 Average pigment value after 60 days of use 300.3 ± 24.8 Average pigment value after 80 days of use 290.9 ± 19.6 Average pigment value after 90 days of use 282.2 ± 24.9

Example 9

Use of MAP Liquid Healthcare Product in Treatment of Melanosis

(73) Take 10 mL of an MAP solution with concentration at 10.0 mg/mL add 10 mL of 0.001% acetic acid solution, and prepare an aqueous solution with the MAP concentration at 5.0 mg/mL.

(74) Gather 12 patients with melanosis diagnosed by dermatologists for test. Use the laser micro-wound technology to create micro-wound surfaces on the testing surfaces of the patients, and then the above MAP liquid healthcare product is used twice per day at an amount capable of completely covering the testing area for 90 days in a row.

(75) Prior to use, measure the melanin value of the affected part and the melanin value of areas surrounding the affected part and having no colored patches. Measure the melanin value of the affected part every 10 to 30 days, and calculate the rate of melanin change at the affected part (see Table 9 for results).

(76) The rate of melanin change is calculated using the following equation:
(melanin value before use−melanin value after use)/(melanin value before use−melanin value of a normal position)×100%

(77) TABLE-US-00009 TABLE 9 Use time (d) Rate of melanin change (%) 10  4.2 ± 1.1 30 25.6 ± 3.8 60 37.1 ± 3.6 90 42.2 ± 3.7

(78) The results show that after using the MAP liquid healthcare product, the pigment value at the affected part has begun to decrease, and along with the extended use time, the rate of the melanin change at the affected part increases. As of 90 days of use, the pigment change at the affected part reaches up to 42.2%, proving that the MAP product according to the present invention can mitigate pigmentation for patients with melanosis, and can be used for treatment of melanosis.

Example 10

Use of MAP Hydrogel Medical Device in Treatment of Melanosis

(79) Mix MAP, Carbomer and propanediol at a mass ratio of 1:1:2 to obtain an MAP hydro-lotion medical device, wherein the MAP concentration is 2.5 mg/mL.

(80) Gather 12 patients with melanosis diagnosed by dermatologists for test. Use the rolling needle micro-wound technology to create micro-wound surfaces on the testing surfaces of the patients, and then the MAP hydrogel medical device is used twice per day at an amount capable of completely covering the testing area for 90 days in a row.

(81) Prior to use, measure the melanin value of the affected part and the melanin value of areas surrounding the affected part and having no colored patches. After using MAP, measure the melanin value of the affected part every 10 to 30 days, and calculate the rate of melanin change at the affected part (see Table 10 for results).

(82) The rate of melanin change is calculated using the following equation:
(melanin value before use−melanin value after use)/(melanin value before use−melanin value of a normal position)×100%

(83) TABLE-US-00010 TABLE 10 Use time (d) Rate of melanin change (%) 10 10.3 ± 1.6 30 23.6 ± 3.1 60 31.8 ± 2.8 90 39.2 ± 3.5

(84) The results show that after 10 days of using the MAP hydrogel medical device, the pigment value at the affected part has begun to decrease, and along with the extended use time, the rate of the melanin change at the affected part increases. As of 90 days of use, the pigment change at the affected part reaches up to 39.2%, proving that the MAP product according to the present invention can mitigate pigmentation for patients with melanosis, and can be used for treatment of melanosis.

Example 11

Use of MAP Liquid Cosmetic in Treatment to Inhibit Melanin Pigmentation After Burns

(85) Take an MAP solution, add 0.01% citric acid to adjust pH to 4.0 and obtain an MAP liquid cosmetic, wherein the MAP concentration is 10.0 mg/mL.

(86) Gather five patients in the healing phase after burns, the burn surface area of the patients is greater than 2% of the human body surface area, and the subjects join the test after voluntarily signing an Informed Consent Form. The patients use the above MAP liquid cosmetic three times per day at an amount each time capable of evenly covering the affected part. During the test, an adjacent area of the same body is selected as the control, namely two areas of the same body are selected, one of which is applied with the above MAP liquid cosmetic (the test group), and the other one thereof is treated according to a normal procedure (the control group). At Day 0, Day 7 and Day 14 of the use, determine pigment for the test group, the control group and the healthy skin, respectively (see Table 11). After 14 days of treatment, no obvious melanin pigmentation is observed on the skin recovered from the burn by using the MAP liquid cosmetic, while obvious pigmentation is observed on the skin that did not use the MAP liquid cosmetic.

(87) TABLE-US-00011 TABLE 11 Pigment of healthy Pigment of skin in Pigment of skin in the skin the test group control group Day 0 138.7 ± 5.8 139.6 ± 6.1 139.6 ± 6.1 Day 7 138.7 ± 5.8 142.6 ± 4.3 157.4 ± 5.5 Day 14 138.7 ± 5.8 145.2 ± 4.9 170.2 ± 6.0