KR20150000242A - Compositions Containing BMP6 for Preventing or Treating Psoriasis and Health Foods Containing BMP6 for Preventing or Improving Psoriasis - Google Patents

Abstract

The present invention relates to a composition for preventing or treating psoriasis including bone morphogenetic protein (BMP6) as an active ingredient and functional food products for promoting health for preventing or improving psoriasis, comprising pharmaceutically acceptable carriers wherein the BMP6 as an active ingredient promotes differentiation and proliferation of keratinocyte in normal cells. In the present invention, the composition can target the keratinocyte and increase the treatment efficiency of psoriasis.

Description

Technical Field [0001] The present invention relates to a composition for prevention or treatment of psoriasis containing BMP6, and a health functional food for preventing or improving psoriasis containing BMP6.

The present invention relates to a composition for preventing or treating psoriasis containing BMP6 (Bone Morphogenetic Protein 6 (Bone Morphogenetic Protein 6)) and a health functional food for preventing or improving psoriasis containing BMP6.

 Psoriasis is a chronic recurrent skin inflammatory disease that develops in the form of silvery white spots covered with erythematous papules. Approximately 3% (125 million) of the world's population are psoriatic patients and about 2% of the population in Korea. Psoriasis is one of the representative chronic inflammatory skin diseases that is difficult to treat because it is characterized by histologically abnormal stratification of the stratum corneum. Therefore, the demand for psoriasis drugs is continuously increasing.

Steroids, which are the most widely used treatments for traditional skin diseases, cause side effects such as diabetes and hypertension, and they have become a social problem due to their abuse. In the case of recently developed immunomodulators, they act only on specific target parts, Antibody agents that were expected to produce inhibitory effects have been reported to cause unexpected serious side effects such as immune disorders, infection, and cancer. Therefore, it was required to select a clearer psoriasis before the generation of the psoriasis and new target factors.

HIF-1, which is recently reported to have increased expression in psoriatic skin tissues, is a transcription factor that maintains intracellular homeostasis by inducing the corresponding process, angiogenesis, etc., in order to respond appropriately to the change of oxygen concentration in the hypoxic state to be. Among them, HIF-1α is a transcription factor of the basic helix-loop-helix-PER-ARNT-SIM (basic-helix-loop-helix- Increased expression and activity of HIF-1α in keratinocytes is known to promote skin inflammation, such as psoriasis, by inducing proliferation of keratinocytes and promoting angiogenesis around the epidermis by activating a dependent signaling pathway (C. Rosenberger et al, Journal of Investigative Dermatology , 127: 2445-52, 2007). In addition, the expression of HIF-1α in the actual psoriatic patient tissue was confirmed by immunohistochemical staining, and the expression was increased compared with normal tissues (M. Ioannou et al, Journal of Cutaneous Pathology , 36 (12): 1255-61, 2009). However, it is not known how HIF-1α overexpression plays a role in the development of psoriasis.

In addition, BMP (bone morphogenetic protein) is present in about 20 subtypes and exhibits numerous biological responses in various stages of developmental and adult cellular tissue. BMP is known to promote differentiation and proliferation of keratinocytes in normal skin, regulates melanogenesis activity, inhibits the initiation of hair follicle development, and in lesion skin, not only newly formed keratinocytes and skin fibroblasts but also chronic It is also known that the expression of BMP6 is increased in wound tissues.

In addition, it has been reported that psoriasis-like skin was observed in transgenic mice overexpressing BMP6 using the K10 promoter. In this animal model, it is reported that overexpression of BMP6 suppresses cell proliferation of epidermal layer, and that expression of BMP6 is weak and rarely increases proliferation of basal epidermal keratinocytes (Blessing M. et al , The Journal of Cell Biology , 135 (1): 227-39,1996). Thus, it is known in the art that BMP6 is overexpressed in the case of psoriasis, and conversely, it has not been possible to treat or prevent psoriasis by treating BMP6.

The present inventors have made intensive efforts to solve the above problems, and as a result, they have found that BMP6 reduces keratinocyte proliferation which is increased upon HIF-1 overexpression, and completed the present invention.

It is an object of the present invention to provide a composition for preventing or treating psoriasis containing BMP6 and a health functional food for preventing or improving psoriasis containing BMP6.

In order to achieve the above object, the present invention provides a composition for preventing or treating psoriasis containing BMP6 as an active ingredient and a health functional food for preventing or improving psoriasis containing BMP6.

When a composition containing BMP6 according to the present invention is used as an active ingredient, the keratinocyte is targeted, which is useful for the treatment of psoriasis because it can enhance the efficiency of psoriasis treatment as compared with therapeutic agents targeting existing immune cells.

1 shows the number of viable cells with CCK-8 after overexpressing HIF-1 in keratinocytes, and FIG. 1B shows the number of viable cells obtained by fluorescence microscopy Image.
FIGS. 2A and 2B show the results of cell cycle analysis using a flow cytometer after PI staining followed by HIF-1 overexpression in keratinocytes. FIG. 2C shows the result of Western blot analysis of Example 1-2 D, E, F and G of FIG. 2 show the expression of differentiation markers confirmed by the real-time PCR method of Example 1-2, respectively. The expression levels of K5, K10, FLG and LOR.
FIG. 3 shows a decrease in expression of BMP6 by overexpression of HIF-1, wherein A represents the change of BMP6 mRNA and B represents the change of BMP6 protein.
FIG. 4A is a schematic diagram of the BMP6 promoter, and FIG. 4B shows the activity of the BMP6 promoter after overexpression of HIF-1.
FIG. 5A shows the number of living cells with CCK-8 after treating keratinocytes with BMP6, and FIG. 5B shows an image of living cells obtained by fluorescence microscopy through Calcine-AM staining of the cells .
6A and 6B show the results of analysis of cell cycle using a flow cytometry analyzer after treating keratinocytes with BMP6, followed by PI staining, and FIG. 6C shows the results obtained by Western blot analysis of Example 2-2 6, D, E, F and G show the expression of the differentiation markers confirmed by the real-time PCR method of Example 2-2, which show K5, K10, FLG and LOR, respectively will be.
FIG. 7A shows the number of living cells as CCK-8 after treatment of BMP6 with keratinocytes in which HIF-1 was overexpressed. FIG. 7B shows the results of fluorescence microscopy FIG. 7C and D show the result of analysis of cell cycle using a flow cytometer after PI staining of normal cells.
8 is a graph showing a decrease in the proliferation of keratinocytes and an increase in the expression of filamentous green by the treatment of BMP6 in the mouse psoriasis model of Example 3. Fig.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature used herein is well known and commonly used in the art.

In the present invention, the increase of keratinocyte and S-keratinocyte proliferation, the decrease of BMP6 expression by HIF-1 and the decrease of keratinocyte and S-keratinocyte cell by BMP6 treatment were analyzed by HIF-1 overexpression. As a result, it was confirmed that BMP6 reduced keratinocyte proliferation which is increased upon HIF-1 overexpression.

That is, in one embodiment of the present invention, it was confirmed that BMP6 reduces keratinocyte proliferation which is increased upon HIF-1 overexpression.

Accordingly, in one aspect, the present invention relates to a composition for preventing or treating psoriasis comprising BMP6 as an active ingredient.

In the present invention, it is characterized in that the BMP6 reduces the proliferation of keratinocytes which are increased upon HIF-1 overexpression.

In the present invention, the composition is characterized by containing a pharmaceutically acceptable carrier, wherein the carrier is selected from the group consisting of ion exchange resins, alumina, aluminum stearate, lecithin, serum proteins, buffer substances, water, , At least one selected from the group consisting of colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, cellulose-based substrate, polyethylene glycol, sodium carboxymethylcellulose, polyarylate, wax, polyethylene glycol and wool.

In the present invention, the composition is formulated for intravenous, intraperitoneal, intramuscular, intraarterial, oral, intracardiac, intramedullary, transdermal, intestinal, subcutaneous, sublingual or topical administration Wherein the composition further comprises at least one adjuvant selected from the group consisting of a buffer, an antibacterial preservative, a surfactant, an antioxidant, a tonicity adjusting agent, an antiseptic, a thickener and a viscosity modifier, Suspensions, emulsions, gels, and powders.

The present invention also relates to a health functional food for preventing or ameliorating psoriasis containing the composition as an active ingredient from a different viewpoint.

The term "composition" as used herein in the context of the present invention is intended to encompass the products containing the specified ingredients, as well as any products made directly or indirectly by the combination of the specified ingredients.

The pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by intraperitoneal injection, intravenous injection, subcutaneous injection, muscle injection, or the like.

The appropriate dosage of the pharmaceutical composition of the present invention will vary depending on factors such as severity of symptoms, body weight, age, sex, mode of administration and time of administration, etc. Usually, the skilled physician will administer effective doses Can be easily determined.

In the present invention, the composition is characterized by containing 0.0001 to 100 mg of BMP6 per kg body weight of the subject to be treated, preferably 0.01 to 50 mg per kg body weight of the subject to be treated.

The pharmaceutical composition of the present invention may be prepared in the form of a unit dose by formulating it using a pharmaceutically acceptable carrier or excipient according to a method which can be easily carried out by a person skilled in the art to which the present invention belongs Into a capacity container. The above carriers include lactose, dextrose, sucrose, sorbitol, acacia, calcium phosphate, gelatin, cellulose, water, syrup, methylhydroxybenzoate, talc, mineral oil and the like which are conventionally used in the formulation , But is not limited thereto. The composition can be used as a preservative such as methyl parahydroxybenzoate or potassium sorbate, a stabilizer, a natural flavor such as a plum flavor or a lemon flavor, a natural coloring matter such as chlorophyllin, a sweetener such as fructose, honey or sugar, May be further contained.

Examples of the agent for parenteral administration of the pharmaceutical composition of the present invention include a sterilized aqueous solution, a non-aqueous solvent, a suspending agent, an emulsion, a freeze-dried preparation and a suppository. Examples thereof include propylene glycol, And injectable esters such as vegetable oil and ethyl oleate may be used. As a suppository, suppositories, macrogol, cacao butter, glycerogelatin and the like may be used, but the present invention is not limited thereto.

The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with another therapeutic agent, and may be administered sequentially or simultaneously with a conventional therapeutic agent.

The health functional food of the present invention refers to a food prepared and processed by using raw materials or ingredients having useful functions in accordance with Law No. 6722 on Health Functional Foods, Physiological function, etc., for the purpose of obtaining a beneficial effect for health food.

The health functional food of the present invention may be formulated into a conventional health functional food formulation known in the art, and the health functional food may be a granular preparation, a tablet, a pill, a suspension, an emulsion, a syrup, a chewing gum, Various beverages, drinks, alcoholic beverages and the like, and there is no particular limitation on the kind of the health functional food.

The health functional food of the present invention may be in any form suitable for administration to an animal body including the human body, more specifically any form usual for oral administration, for example, additives and adjuvants for food or feed, food or feed, Such as tablets, pills, tablets, pills, tablets, pills, granules, capsules, and foamed formulations, or in the form of liquids such as solutions, suspensions, emulsions, beverages, pastes and the like and may be in the form of nutrients, vitamins, electrolytes, sweeteners, Etc., and these components may be used independently or in combination.

[Example]

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for illustrating the present invention and that the scope of the present invention is not construed as being limited by these embodiments. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.

Example  One: HIF -1 BMP6 Control of

1-1: HIF -1 Overexpression Increases proliferation of keratinocytes

In order to confirm the hyperproliferation of keratinocytes, HIF-1 was overexpressed in keratinocytes and the degree of keratinocyte proliferation was checked with CCK-8 (Woongbi, Korea) over time. As a result, (Fig. 1, A). Then, on the fifth day of experiment, it is a substance which is easy to get into cell with hydrophobic substance which is not fluorescence originally. It enters into living cell and turns into calcein by intracellular esterase and becomes green fluorescence, (Sigma, USA) at 37 ° C for 10 minutes and then confirmed by fluorescence microscopy (FIG. 1B).

1-2: HIF -1 overexpression of proliferating S-keratinocytes

To confirm whether hyperproliferation of keratinocytes is related to cell cycle changes, HIF-1 was overexpressed and keratinocytes were stained with propidium iodide (PI) and analyzed by flow cytometry. Specifically, pcDNA3-no insert and pcDNA-HIF-1a (P402A, P564A) were transfected into human keratinocytes (Millipore, USA) using lipofectamine 2000. After 48 hours, Ethanol for 1 hour, washed, and reacted with 0.5 mg / ml RNase (Sigma, USA) at 37 ° C for 1 hour. Then, 10 ug / ml PI solution was added and the cell cycle was analyzed with a flow cytometer (BD, USA). As a result, it was confirmed that S phase cells, which are proliferative cells, were increased in keratinocytes in which HIF-1 was overexpressed (FIGS. 2A and 2B).

In addition, in order to confirm the increase of the cell cycle by a certain cell cycle regulator, expression of interest involved in the cell cycle was confirmed by Western blotting. Specifically, pcDNA3-no insert and pcDNA-HIF-1a (P402A, P564A) were transfected into human keratinocytes (Millipore, USA) using lipofectamine 2000. After 48 hours, RIPA buffer , Korea) and allowed to stand in ice for 30 minutes. After centrifugation at 13000 rpm for 30 minutes in a refrigerated centrifuge, the supernatant was taken and the protein was quantitatively analyzed. Then, 50 μg of the protein was loaded on the SDS-PAGE gel. The PVDF-loaded gel was then transferred, blocked with 5% BSA for 1 hour, and incubated with CKD2, CDK4, CDK6 or Actin antibody (Cell Signaling, USA) diluted 1: 1000. After the HRP-conjugated secondary antibody reaction and washing, ECL solution was used to identify the protein band. As a result, it was confirmed that the expression of CDK2, which is known to increase expression in S phase, was increased more than two times when HIF-1 was overexpressed (FIG. 2C). It can be seen that the differentiation and proliferation of keratinocytes are closely controlled and controlled.

(K10), filaggrin (FLG), which are known to increase expression at the normal differentiation of keratinocytes by real-time PCR, in order to determine whether the expression of keratinocyte differentiation factor ), Loricrin (LOR), and keratin-5 (K-5) expression, which is increased during keratinocyte differentiation. Specifically, pcDNA3-no insert and pcDNA-HIF-1a (P402A, P564A) were transfected into human keratinocytes (Millipore, USA) using lipofectamine 2000. After 48 hours, TRIzol reagent was added Then, the RNA was separated by grinding using a homogenizer. The isolated RNA was used to prepare cDNA for each tissue using reverse transcriptase (Super-bio, Korea). (SEQ ID NO: 1) and K5 primer-R (SEQ ID NO: 2), K10 primer-F (SEQ ID NO: 3) and K10 primer- F (SEQ ID NO: 5) and FLG primer-R (SEQ ID NO: 6), LOR primer-F (SEQ ID NO: 7) and LOR primer- 35 cycles were carried out using one cycle of denaturation step (95 ° C., 30 seconds), annealing step (56 ° C., 30 seconds) and extension step (72 ° C., 40 seconds) Respectively. As a result, the expression of FLG and LOR was decreased upon HIF-1 overexpression (D, E, F, and G of FIG. 2). This result shows that abnormal differentiation of keratinocytes can be induced by overexpression of HIF-1 in keratinocytes.

1-3: Microarray  through HIF -1 of Target factor  Selection

HIF-1 overexpression, as well as the proliferation of keratinocytes, as well as the ability to regulate differentiation, may be attributed to HIF-1 as a marker of differentiation. HIF-1 Targeting factors were selected. RNA was extracted from the keratinocytes transfected with the HIF-1 plasmid and the keratinocytes transfected with the no insert plasmid and microarray was performed using a 4x44k array chip (Agilent, Korea). As a result, expression of BMP6, which is involved in the differentiation of keratinocytes, was selected as a target factor. HIF-1 overexpressed keratinocyte expression was reduced to about half, and HIF-1 binding site was found on the promoter.

1-4: HIF -1 BMP6  Identification of reduced gene expression

After HIF-1 plasmid was transfected into keratinocytes, 24 hours after HIF-1 overexpression, real-time PCR and Western blotting revealed that the expression of BMP6 mRNA and protein was reduced (FIG. 3). Western blot is similar to Example 1-2 except that BMP6 (R & D, USA), HIF-1α (BD, USA) or Actin antibody (Cell Signaling, USA) was diluted 1: 1000. In addition, in the case of real-time PCR, except for using BMP6 primer-F (SEQ ID NO: 11) and BMP6 primer-R (SEQ ID NO: 12), GAPDH primer-F (SEQ ID NO: 9) and GAPDH primer- Is the same as in Example 1-2.

1-5: HIF -1 BMP6 Control of

In order to confirm the regulation of BMP6 molecule reduced by HIF-1 overexpression, it was confirmed that HIF-1 binding site exists in the promoter of BMP6 gene in bioinformatics aspect. Analysis of the transcription factors binding to the BMP6 promoter using a matrix-inspector (Genomatix) confirmed the presence of the HIF-1 binding site in the promoter of the BMP6 gene (Fig. 4A).

In addition, the activity of luciferase (Promega, USA) was measured after transfection of pcDNA3-no insert, pcDNA-HIF-1a (P402A, P564A) plasmid and pGL3-BMP6 promoter plasmid into keratinocytes, -1 was increased, the promoter activity of BMP6 was lowered (FIG. 4B). That is, it was found that HIF-1 regulates the transcription of BMP6, thereby decreasing the expression level.

Example  2: BMP6  By treatment Psoriasis treatment

2-1: BMP6  Inhibition of keratinocyte cell proliferation by treatment

BMP6 protein was treated with keratinocytes at various concentrations and the degree of cell proliferation with time was confirmed using CCK-8. As a result, it was found that the proliferation of keratinocytes was decreased in a concentration-dependent manner by treatment with BMP6 (FIG. 5A). On the fifth day of the experiment, living cells were identified by fluorescence microscopy through Calcine-AM staining (Fig. 5B).

2-2: BMP6  Cell cycle control of keratinocytes by treatment

As a result of confirming whether the decrease of keratinocyte proliferation rate by BMP6 treatment is related to inhibition of cell cycle, it was confirmed that, in contrast to the case of HIF-1 overexpression, the number of S phase cells in the group treated with BMP6 decreased (Fig. PI staining, Western blotting, and real-time PCR were performed in the same manner as in Example 1-2 except that the BMP6 protein was treated for 18 hours.

2-3: HIF By -1 Increased  Keratinocyte BMP6  Proliferation inhibition by treatment

HIF-1 over-expressing cells were treated with BMP6 protein to induce HIF-1 overexpression. In order to examine whether the proliferation of keratinocytes during HIF-1 overexpression was due to a decrease in BMP6 expression, . As a result, it was found that the degree of proliferation decreased upon treatment with BMP6 (FIGS. 7A and 7B).

In addition, the reduction of HIF-1 overexpressed keratinocytes by BMP6 treatment was correlated with cell cycle inhibition, indicating that the S group of BMP6-treated cells decreased (C and D in Fig. 7).

Example  3: BMP6  Protein psoriasis  Therapeutic efficacy verification experiment

In order to examine the efficacy of BMP6 protein for psoriasis, an animal model in which psoriasis was induced by applying imiquimod (IMQ) to mouse skin was used. One day, 62.5 mg of IMQ cream (Sigma, USA) was applied to Balb / c mice at 5 weeks of age for 9 days to induce psoriasis-like skin. Then, 5 ug of BMP6 protein was subcutaneously injected to the IMQ application site for 6 days from day 7 of IMQ treatment, and PBS was subcutaneously injected into IMQ application site as a control group.

The results were analyzed by immunohistochemistry. Specifically, mice were sacrificed and skin tissues were collected, fixed in 4% formaldehyde (Sigma, USA), embedded in paraffin, and slides were prepared. After the tissue slides were subjected to a dephosphorylation process using xylene and a dehydration process using alcohol, the slides were immersed in a citrate buffer, and the slides were rotated in a microwave oven for 10 minutes and then cooled at room temperature for one hour. Washed with distilled water and reacted with 5% goat serum for 1 hour at room temperature, followed by dilution with Fila green antibody at 1:50 and incubation. HRP-conjugated secondary antibody was reacted and DAB kit was used for color development to confirm the expression of pilar green in the tissues.

As a result, it was confirmed that the group treated with IMQ and PBS significantly increased the thickness of the stratum corneum compared to the group treated with PBS alone, resulting in psoriasis. In addition, the IMQ and BMP6-treated groups showed a roughly ½ thickness reduction of the stratum corneum compared to the IMQ and PBS-treated groups, and they were not only expressed at the last stage of differentiation, It was confirmed that the expression of green was increased (Fig. 8).

Therefore, the treatment of BMP6 with psoriasis tissue inhibited the proliferation of keratinocytes and showed the effect of treating psoriasis.

While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. something to do. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

<110> Korea University Research and Business Foundation <120> Compositions Containing BMP6 for Preventing or Treating Psoriasis          and Health Foods Containing BMP6 for Preventing or Improving          Psoriasis <130> P13-B127 <160> 12 <170> Kopatentin 2.0 <210> 1 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> K5 primer F <400> 1 tctcgccagt caagtgtgtc 20 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> K5 primer R <400> 2 atagccaccc actccacaag 20 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> K10 primer F <400> 3 tcgctactgt gtgcagctct 20 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> K10 primer R <400> 4 cggaacttcc ctctccttct 20 <210> 5 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> FLG primer F <400> 5 ggtctggacg ttcagggtct 20 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> FLG primer R <400> 6 ggatgtggtg tggctgtgat 20 <210> 7 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> LOR primer F <400> 7 gggcaccgat gggcttag 18 <210> 8 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> LOR primer R <400> 8 ggtaggttaa gacatgaagg attt 24 <210> 9 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> GAPDH primer F <400> 9 ccatgttcgt catgggtgt 19 <210> 10 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> GAPDH primer R <400> 10 ccaggggtgc taagcagtt 19 <210> 11 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BMP6 primer F <400> 11 gaagatctat tcccgggtct tg 22 <210> 12 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> BMP6 primer R <400> 12 cccaagcttc accaccagca cagc 24

Claims (7)

A composition for preventing or treating psoriasis comprising BMP6 (Bone Morphogenetic Protein 6) as an active ingredient.
The composition for preventing or treating psoriasis according to claim 1, wherein the BMP6 reduces keratinocyte proliferation which is increased upon HIF-1 overexpression.
The composition for preventing or treating psoriasis according to claim 1, which comprises a pharmaceutically acceptable carrier.
The method of claim 3, wherein the carrier is selected from the group consisting of ion exchange resins, alumina, aluminum stearate, lecithin, serum proteins, buffer substances, water, salts, electrolytes, colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, Wherein the composition is at least one selected from the group consisting of polyethylene glycol, sodium carboxymethyl cellulose, polyarylate, wax, polyethylene glycol, and wool.
The use according to claim 1, wherein the formulation is for intravenous, intraperitoneal, intramuscular, intraarterial, oral, intracardiac, intramedullary, intrathecal, transdermal, intestinal, subcutaneous, sublingual or topical administration. &Lt; / RTI &gt;
The composition for preventing or treating psoriasis according to claim 1, further comprising at least one adjuvant selected from the group consisting of a buffer, an antibacterial preservative, a surfactant, an antioxidant, a tonicity adjusting agent, an antiseptic, a thickener and a viscosity modifier .
A health functional food for preventing or improving psoriasis containing BMP6 as an active ingredient.

Images