JP2021134160A - Melanogenesis inhibitor, skin-whitening agent, topical skin preparation for skin whitening, method for producing hydroxymethyl furfural, and device for producing hydroxyl furfural - Google Patents

Abstract

To provide a melanogenesis inhibitor containing a compound having high melanogenesis inhibitory activity as an active ingredient, and a skin-whitening agent and a topical skin preparation for skin whitening.SOLUTION: Prepared are a melanogenesis inhibitor containing hydroxymethyl furfural as an active ingredient, a skin-whitening agent containing hydroxymethyl furfural as an active ingredient, and a topical skin preparation for skin whitening containing the melanogenesis inhibitor.SELECTED DRAWING: Figure 7

Description

The present invention relates to a melanin production inhibitor, a whitening agent, and a skin external preparation for whitening. More specifically, hydroxymethylfurfural (5-hydroxymethyl-2-flualdehyde, 5-HМF) having a high melanin production inhibitory activity is effective. It relates to a melanin production inhibitor as an ingredient, a whitening agent, and an external skin-whitening agent.

Melanin is a brown to black pigment formed in animals including humans, plants, protozoa, and some bacterial cells. In vertebrates, this melanin is mostly produced by melanocytes (pigment cells) in the basal layer of the lowest layer of the epidermis of the skin and the hair matrix of the hair. This melanocyte only has the function of producing melanin, not the cell that stores melanin. Melanin is tightly bound to proteins.

Melanin is one of the factors that determine skin color in humans, and plays an important role in protecting the body from the harmful effects of ultraviolet rays. Excessive production of melanin is considered to be the cause of darkening, and the appearance of spots and freckles due to the uneven distribution of the produced melanin is also called cosmetic defect and skin aging. Recently, melanin is produced through the melanin production pathway starting from tyrosine by activating tyrosinase in melanocytes existing in the basal part inside the skin by active oxygen generated inside the skin due to ultraviolet rays, stress, etc. It is said that after being synthesized and stored in vesicles called melanosomes, it is transferred to keratinocytes of the skin and causes a change in skin color.

Thus, the cosmetics industry and the like are required to develop more effective melanin production inhibitors, whitening agents, and external skin whitening agents for the purpose of preventing darkening of the skin caused by melanin production and whitening. For this purpose, prior art has been proposed for substances having many melanin production inhibitory effects, including the use of L-ascorbic acid, which is said to have a reducing effect on produced melanin (see, for example, Patent Document 1). ..

On the other hand, hydroxymethylfurfural, in other words, this metabolite (5-HМFA) can prevent the occurrence of causes of lifestyle-related diseases such as hyperlipidemia, diabetes, arteriosclerosis, thrombosis, and pneumonia, and maintain health. It is a compound that has the effect of, for example, a compound that can be added to foods such as soups, sauces, jams, coffee, etc. to make it a useful food without damaging the original flavor. (See, for example, Patent Document 2).
However, it is not known that hydroxymethylfurfural has a melanin production inhibitory effect and a whitening effect.

Japanese Unexamined Patent Publication No. 2007-177119 Japanese Unexamined Patent Publication No. 2008-193933

An object of the present invention is to solve the above-mentioned problems of the prior art, such as a melanin production inhibitor containing hydroxymethylfurfural, which is a compound having high melanin production inhibitory activity and has high safety, as an active ingredient, and hydroxymethyl. It is an object of the present invention to provide a whitening agent containing furfural as an active ingredient and an external skin whitening agent containing this melanin production inhibitor.

The melanin production inhibitor of the present invention is characterized by containing hydroxymethylfurfural (5-HMF) as an active ingredient.
The whitening agent of the present invention is characterized by containing the melanin production inhibitor as an active ingredient.
The external preparation for whitening skin of the present invention is characterized by containing the melanin production inhibitor as an active ingredient.

In the method for producing hydroxymethylfurfural of the present invention, the juice obtained by squeezing the fruit juice is heat-concentrated or honey is heat-concentrated, and the obtained concentrate is dried to dry hydroxymethylfurfural (5-hydroxymethyl-). 2-Furfural (5-HMF)) is obtained.

The hydroxylfurfural production apparatus of the present invention is a means for heat-concentrating squeezed fruit juice or heat-concentrating honey using a squeezing means for squeezing fruit juice, and drying the obtained concentrate to obtain hydroxymethylfurfural. It is characterized by having means.

The melanin production inhibitor containing hydroxymethylfurfural (5-HMF) as an active ingredient according to the present invention is useful as an agent for improving or preventing skin stains and freckles caused by melanin production, a whitening agent, and an external skin whitening agent. It has the effect of being.

It is a graph showing ^{1 H} nuclear data of the active ingredient in the present invention (showing that it is a six with compound H). Is a graph showing ^{1 H} nuclear data of the active ingredient in the present invention (doublet peak is broken into two), From this, the 2 H atoms, "each other in the meta position adjacent or aromatic ring You can see that it is "arranged". ^{It is a graph which shows the data of 13} C NMR and DEPT of the active ingredient in this invention, respectively. (a) From the data of DEPT, CH ₁ and CH ₃ are seen above, CH ₂ is seen below, and grade 4 is Not visible, (b) From the ¹³ C NMR data, it can be seen that all C atoms are visible and contain 6 C atoms. The COSY spectrum showing the positional relationship between the Hs of the active ingredients in the present invention is shown, and the correlation between the H atom and the H atom is shown (it can be seen that there is a correlation between b and c). The HMBC spectrum showing the positional relationship between the H atom and the C atom of the active ingredient in the present invention is shown (the position of the H atom and the C atom can be known). It is a graph which confirms the production by HPLC about the active substance in this invention, and shows that the purity is about 75% before an open column, and 99.8% after an open column. It is a graph which shows the data explaining the tyrosinase inhibitory effect (whitening effect) of 5-HMF of an active substance in this invention. It is data for demonstrating the influence which 5-HMF of the active substance in this invention has on the expression of tyrosinase. It is a graph for demonstrating the influence which 5-HMF of an active substance in this invention has on a tyrosinase transcription factor. It is a graph for demonstrating the influence which 5-HMF of the active substance in this invention has on the cAMP signal pathway. It is a graph which shows the summary of FIGS. 8-10.

Hereinafter, a method for producing a melanin production inhibitor, a whitening agent containing a melanin production inhibitor as an active ingredient, a skin external preparation for whitening containing a melanin production inhibitor, and hydroxymethylfurfural (5-HMF) according to the present invention will be carried out. The form will be described with reference to the drawings. First, the outline of the embodiment will be described, and then the individual components will be described in detail.

According to the embodiment of the melanin production inhibitor according to the present invention, the melanin production inhibitor is not particularly limited as long as it contains hydroxymethylfurfural (5-HMF) as an active ingredient, and is not particularly limited. According to the embodiment of the whitening agent, the whitening agent is not particularly limited as long as it contains the above-mentioned melanin production inhibitor as an active ingredient, and the embodiment of the external skin whitening agent of the present invention. According to the above, there is no particular limitation as long as it contains the above-mentioned melanin production inhibitor.

According to the embodiment of the method for producing hydroxymethylfurfural according to the present invention, the squeezed fruit juice of a fruit (preferably a non-standard 20th century pear (of course, a non-standard pear)) is heated and concentrated, or The honey is concentrated, an ethanol solution (for example, 1: 4 v / v) is added to the obtained concentrate, and the mixture is shaken for a predetermined time (for example, about 30 minutes), and the obtained extract is concentrated with a rotary evaporator. Then, appropriately dilute with distilled water, _{activate the resin (Cosmosil 140C 18-} OPN) with ethanol, fill the column, equilibrate with distilled water, apply the sample, and show absorption at 280 nm. Is collected and concentrated, and the obtained concentrate is subjected to reverse phase HPLC analysis (confirmation of purity), lyophilized, and the dried product is structurally analyzed. As a result of the analysis, hydroxymethylfurfural (5-hydroxymethyl-2-furfural (5-HMF)) is obtained. As a result of this HPLC analysis, β-arbutin is reduced and 5-HMF is expressed in 8 to 9 minutes.

In the present invention, according to an embodiment of an apparatus for producing hydroxymethylfurfural, this apparatus is preferably a means for heating and concentrating fruit juice or concentrating honey, 280 nm by a reverse phase HPLC method. It has a means for collecting fractions having absorption of the above, and a means for freeze-drying the collected fractions to obtain hydroxymethylfurfural.

For example, when the 20th century pear juice is concentrated by heating, it is clear that the juice before heating contains a large amount of substances that are rarely contained, and that it has an inhibitory effect on tyrosinase (an enzyme that causes stains). Became. In order to clarify what this substance is, the substance was purified from a heated concentrated solution of 20th century pear juice. After confirming that purification was possible by HPLC, the purity was increased so that the structural analysis could be performed accurately.

In order to clarify the structure of the substance, FIGS. 1 to 5 show an analysis of how many hydrogen atoms and carbon atoms are contained in the molecule, and as a result, the structure shown in the following formula (I) is obtained. It was identified to have.

As is clear from FIGS. 1-5, it was clear that the obtained substance was 5-hydroxymethyl-2-furfural (5-HMF). FIG. 6 is a diagram confirming whether purification can be performed by HPLC. As a result, the purity was increased (purity 99%), and the structural analysis in the invention could be performed accurately.

As shown in FIG. 7 (graph showing the results by the Dixon plot method), it is clear that 5-HMF can inhibit the activity of tyrosinase. Tyrosine converts tyrosine to dopa and also dopa to dopaquinone (vsL-tyrosine: monophenolase). It also converts dopaquinone to melanin (vsL-dopa: diphenolase). Thus, the substance (5-HMF) was added to tyrosine and dopa to which tyrosinase was added, and the concentrations of tyrosine and dopa after the addition were examined. Since both are high, it is considered that the activity of tyrosinase was inhibited (mixed inhibition).

Examples of the types of external skin whitening agents include basic cosmetics for limbs or bodies such as sunscreens, lotions, emulsions, creams and facial masks, and makeup cosmetics such as foundations, white powder, blushers, lipsticks and eye shadows. Can be mentioned. Examples of the dosage form of the external preparation for whitening skin include liquid, powder, solid, stick, milky liquid (oil-in-water type / water-in-oil type), cream-like, and gel-like.

The above and hydroxymethyl furfural (5-HMF), a is represented by the following formula (I) 5-hydroxymethyl-2-furfural compound _{(C 6 H 6 O 3)} , the result of the analysis, as described below , All physical characteristics matched with commercially available reagents.

According to the structural analysis data of the compound which is the active ingredient in the present invention shown in FIGS. 1 to 5, it was found that this compound is a known compound (5-HMF) having the following chemical structure. Therefore, when the physical characteristics of the commercially available 5-HMF reagent (manufacturing company: Tokyo Chemical Industry Co., Ltd.) and the physical characteristics of the active ingredient (I) of the present invention were compared, all the physical characteristics were in agreement.

（Ｉ）

(I)

As a method for producing or obtaining hydroxymethylfurfural represented by the above formula (I) used in the present invention, a method for extracting and separating from fruits (for example, non-standard (within) 20th century pear) and other methods are used. A method can be considered, but there are no particular restrictions. For example, 5-HMF is used as a quality standard for honey and is obtained by heating sugar, so that it contains sugar other than 20th century pears (for example, other fruits containing sugar and protein). If so, it can be used without limitation and can be extracted from anything. Examples of other fruits include apples, watermelons, citrus fruits, melons and the like.

The melanin production inhibitor, whitening agent, and external skin whitening agent of the present invention include a crude product in the purification process, and are usually used as a melanin production inhibitor or whitening agent as long as the melanin production inhibitory activity is not impaired. Contains activators, disintegrants, binders, lubricants, diluents, buffers, isotonic agents, preservatives, wetting agents, emulsifiers, dispersants, stabilizers, solubilizers, etc. contained in the agent. Compositions may be included.

The melanin production inhibitory activity of the melanin production inhibitor of the present invention is not particularly limited as long as it is an activity that suppresses the action of suppressing the darkening of the body color of the skin and the like associated with the production and accumulation of melanin. The whitening action of the whitening agent and the external skin whitening agent of the present invention includes not only a positive whitening action for whitening the skin but also a passive whitening action for suppressing the darkening of the skin, for example, stains and buckwheat. It also includes a whitening effect that suppresses pigmentation such as.

Regarding the method for determining the presence or absence of inhibitory activity in the melanin production inhibitor of the present invention, for example, DMEM medium (10% (v / v) fetal bovine serum (FBS)), 1% (v / v) penicillin / on a plate. B16 cells were seeded on 3 mL of streptomycin) so as to have 5.0 × 10 ⁴ cells / mL, and after standing at 37 ° C. for 24 hours at a carbon dioxide concentration of 5 v / v%, implantation of the cells was confirmed. Then, the melanocyte-stimulating hormone α-MSH (final concentration (10 nM)) was added, then 5-HMF was added, dissolved in sterile water, and the final concentration of 5-HMF was 0, 17, 34, 170, It was set to 340 ng / mL. After allowing to stand for 72 hours, the cells are collected, and the following various experiments are performed using the cells to visually evaluate and judge the degree of whitening of the cells as compared with the control to which no sample is added. Can be mentioned.

The melanin production inhibitor of the present invention is a whitening agent for improving or preventing, for example, spots, freckles, sunburn, etc., and skin for whitening, as a means for improving the condition caused by the above-mentioned melanin production action. It can be used as a drug for external use, quasi-drugs, etc.

Further, in preparing the melanin production inhibitor of the present invention as a pharmaceutical product, a quasi drug, etc., an activator, a disintegrant, a binder, a lubricant, a diluent, a buffer, an isotonic agent, a preservative, etc. It may be appropriately mixed with additives such as a wetting agent, an emulsifier, a dispersant, a stabilizer, and a solubilizing agent, diluted, dissolved, and blended. Examples of the dosage form in this case include dosage forms such as ointments, liquids, patches, emulsions, solutions, gels and lotions, packs and powders. It can also be used orally or parenterally depending on the purpose of treatment.

The external preparation for whitening skin of the present invention may contain, in addition to hydroxymethylfurfural (5-HMF) as an active ingredient, an ingredient usually blended in the external preparation for whitening skin. For example, at least one selected from the following oily components, powder components, aqueous components, surfactants, antioxidants, preservatives, skin anti-aging agents, UV protection agents, anti-inflammatory agent components, etc. It may be appropriately blended in an amount within a range that does not interfere with the action and effect of the present invention.

The oily component can be blended without particular limitation as long as it can be normally blended in a whitening external preparation for skin. For example, animal oils, vegetable oils, synthetic oils, oils and fats based on them, waxes, hydrocarbons, hydrogenated oils and the like are included.

As the powder component, any powder component that can be usually blended in a whitening external preparation for skin can be blended without particular limitation. As long as it is a powder, it may be an inorganic powder or an organic powder regardless of its shape, particle structure, and the like. For example, specifically, various resin powders such as titanium oxide and zinc oxide are included.

The aqueous component can be added without particular limitation as long as it can be usually added to a whitening external preparation for skin. For example, lower alcohols, glycols, glycerol and the like are included. Specifically, water, ethyl alcohol, butyl alcohol and the like are included.

The surfactant may be blended without particular limitation as long as it can be usually blended in a whitening external preparation for skin. For example, nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants and the like are included.

The antioxidant may be blended without particular limitation as long as it can be usually blended in an external preparation for whitening skin. For example, α-tocopherol, ascorbic acid and the like can be mentioned.

As the preservative, any preservative that can be usually blended in a whitening skin external preparation can be blended without particular limitation. For example, paraoxybenzoic acid ester, phenoxyethanol and the like can be mentioned.

The skin anti-aging agent can be added without particular limitation as long as it can be usually added to a whitening external preparation for skin. For example, coenzyme Q10, retinol, retinoic acid and the like can be mentioned.

The ultraviolet protective agent can be blended without particular limitation as long as it can be usually blended in a whitening external preparation for skin. For example, benzophenone-based compounds, sartylic acid-based compounds and the like can be mentioned.

The anti-inflammatory agent component can be added without particular limitation as long as it can be usually added to a whitening external preparation for skin. For example, allantoin, sulfur, sulfur derivatives, glycyrrhizin, glycyrrhizin derivatives and the like can be mentioned.

In the present invention, the blending ratio of hydroxymethylfurfural (5-HMF) in the external preparation for whitening skin is not particularly limited as long as the action / effect of the present invention is exhibited and the action / effect is not impaired. The minimum concentration at which this 5-HMF can be added to have a whitening effect may be at least 0.0214387 mg / mL of external preparation. At 0.0428774 mg / mL, which is twice that concentration, cytotoxicity may occur, so it is desirable to use at a concentration lower than this concentration. By the way, in order to obtain 5-HMF of 0.0214387 mg / mL to 0.0428774 mg / mL, the blending amount of the pear juice heated concentrate was 3.58 to 7.14% by weight.

In relation to a substance (drug) having a function of suppressing melanin synthesis, such as a melanin production inhibitor (melanin production inhibitor), it is considered that the effect of 5-HMF on the tyrosinase transcription factor may be related. .. That is, as shown in FIGS. 8-11, the effect of 5-HMF on tyrosinase expression was shown based on the cAMP signaling pathway (FIG. 8), and a predetermined amount (170 μm) of 5-HMF inhibited tyrosinase. The effect of 5-HMF on the tyrosinase transcription factor is shown (FIG. 9), the effect of 5-HMF on the cAMP signaling pathway is shown (FIG. 10), and the cAMP signaling pathway is shown (FIG. 11). Thus, it is clear that 5-HMF reduces mRNA and protein expression of MITF, a transcription factor for tyrosinase.
Hereinafter, the present invention will be described in detail with reference to Examples and Comparative Examples. The technical scope of the present invention is not limited to these examples.

(Melanin production inhibitory effect and cell viability test using B16 melanoma cultured cells)
Using B16 melanoma cultured cells derived from mice, hydroxymethylfurfural (5-HMF) was used as a sample to examine the melanin production inhibitory effect and cell viability.

Take an appropriate amount (3 mL) of DMEM medium containing 10% v / vFBS (Biogest) (Life Technologies (currently Thermo Fisher Scientific)) on a 3.5 cm plate, and add B16 melanoma cells (RCB1283 RIKEN BioResource Research Center). The cells were seeded at 5.0 × 10 ⁴ cells / mL and allowed to stand at 37 ° C. for 24 hours at a carbon dioxide concentration of 5 v / v%. After confirming that the cells have been implanted, the final concentration of αMSH (manufactured by Wako Pure Chemical Industries, Ltd. (currently Fuji Film Wako Pure Chemical Industries, Ltd.)), which is a melanin production stimulating hormone, is adjusted to 10 nM (3 μL of 10 μM αMSH solution is added). And allowed to stand again at 37 ° C. for 24 hours under the condition of carbon dioxide concentration of 5 v / v%. Then, hydroxymethylfurfural (manufactured by Tokyo Chemical Industry Co., Ltd.) is dissolved in an appropriate amount of sterilized water, treated with a sterilization filter (manufactured by Toyo Filter Paper Co., Ltd.), and then treated with sterilized water at 1.7, 3.4, 17, and 34 mM hydroxymethyl. A furfural solution was prepared. 30 μL of each concentration of hydroxymethylfurfural solution was added to the above cell culture medium, and the final concentration was set to 0 (control; 30 μL of sterile water was added), 17, 34, 170, 340 μM. After adding the hydroxymethylfurfural solution of each concentration, the cells were mixed and cultured under the above conditions for about 3 days until the cells became about 70% conferted. Ten plates for each culture condition were prepared. The cultured B16 melanoma cells are washed with PBS solution (Phosphate Buffered Saline, pH 7.4, Life Technologies (currently Thermo Fisher Scientific)) and then plated with trypsin solution (Life Technologies (currently Thermo Fisher Scientific)). It was peeled off from the above, recovered, and then washed again with PBS solution.

[Cell viability test]
The collected nB16 melanoma cells were suspended in an appropriate amount of cell culture medium (1 to 2 mL), and 10 μL of the cell suspension and 10 μL of the trypan blue solution were placed in a microtube and mixed. 10 μL of the mixed solution was inserted into a cell counting slide (manufactured by BioRad), and the number of cells and the number of viable cells were measured with a ^{TC20 TM cell counter (manufactured by BioRad).} The viable cell rate (%) at the concentration after each sample was prepared was calculated. The results are shown below.

・数字は平均値±ＳＤ、※は有意差あり（ｐ<０．０５）
・この表は対照（０）の値を１００％にした際の相対値（％）で算出

・ Numbers are average ± SD, * is significantly different (p <0.05)
・ This table is calculated by the relative value (%) when the value of control (0) is set to 100%.

As is clear from Table 1, the amount of 5-HMF is 170 μM, and the whitening evaluation tends to be good (the melanin content is low). In addition, the cell viability tends to be less toxic to some extent when the 5-HMF content is about 34 μM or 170 μM.

Moreover, when the effect of hydroxymethylfurfural on the melanin content of B16 cells was examined, cytotoxicity was shown at 340 μM, so 170 μM or less is considered to be the preferable upper limit. It should be noted that there is a tendency that there is a slight inhibitory effect at about 34 μM.

[Example 1: Toner]
(1) Polyoxyethylene (20EO) sorbitan monolauric acid ester, ethyl alcohol, and ascorbic acid palmitic acid ester, 1.2, 12.0, 0.1% by mass, and preservatives and fragrances, respectively. , Each of them is mixed and dissolved in an appropriate amount. (2) Next, glycerin and 1,3-butylene glycol, 5.0 and 6.5% by mass, ascorbic acid ester sodium, ascorbic acid glucoside, lactic acid, sodium lactate, and collagen, respectively, 0.5, respectively. 2.0, 0.05, 0.1, and 1.0% by mass, and purified water are mixed and dissolved. The above (1) and (2) are mixed to prepare a lotion. Hydroxymethylfurfural is contained in this lotion in an amount of 0.0214387 mg / mL or more and less than 0.0428774 mg / mL based on the melanin production inhibitor standard.

[Example 2: Cleanser]
(1) Lauric acid, myristic acid, stearic acid, glycerin, polyethylene glycol 1500, potassium hydroxide, and purified water were added to 5.0, 18.5, 6.0, 12.0, 5.0, 6 respectively. .5 and a predetermined amount (remaining amount) are heated and melted. (2) Coconut oil fatty acid diethanolamide, coconut oil fatty acid methyl taurine sodium, polyoxyethylene (7.5 E.O.) lauryl ether, and ethylene glycol distearate were added to 5.0, 1.8, and 2.0, respectively. Heat and dissolve mass%. Add (2) to (1) and mix. The mixture is cooled, then a 1% aqueous solution of hydroxypropylmethylcellulose and a fragrance are added and mixed to give a cleanser. Hydroxymethylfurfural is contained in this facial cleanser at 0.0214387 mg / mL or more and less than 0.0428774 mg / mL based on the melanin production inhibitor standard.
All of the cosmetics produced as described above were excellent in diametrical stability, and when applied to the skin, an excellent whitening effect could be brought about.

According to the present invention, a melanin production inhibitor containing hydroxymethylfurfural as an active ingredient, which has a melanin production inhibitory effect, a whitening agent containing hydroxymethylfurfural as an active ingredient, and an external skin whitening agent containing this melanin production inhibitor. It is useful in the field of cosmetics industry where whitening effect is required.

The melanin production inhibitor of the present invention is characterized by containing hydroxymethylfurfural as an active ingredient at 3.4 μmol / L or more and 170 μmol / L or less. Further, the melanin production inhibitor of the present invention preferably contains hydroxymethylfurfural as an active ingredient at 3.4 μmol / L or more and 170 μmol / L or less, and the whitening agent of the present invention preferably contains the melanin production inhibitor. It is characterized by containing an agent as an active ingredient.
The external preparation for whitening skin of the present invention is characterized by containing the melanin production inhibitor as an active ingredient.

Method for producing a melanin production inhibitor of the present invention, the twentieth century pear juice was juice allowed to thermally concentrated resulting from squeezing, is dried and the resulting concentrate to give the hydroxymethyl furfural, resulting hydroxy It is characterized in that a melanin production inhibitor is produced by containing methylfurfural as an active ingredient at 3.4 μmol / L or more and 170 μmol / L or less.

Claims (5)

A melanin production inhibitor characterized by containing hydroxymethylfurfural as an active ingredient. A whitening agent containing the melanin production inhibitor according to claim 1 as an active ingredient. An external preparation for whitening skin, which comprises the melanin production inhibitor according to claim 1 as an active ingredient. A method for producing hydroxymethylfurfural, which comprises heat-concentrating fruit juice obtained by squeezing fruit juice or heat-concentrating honey, and drying the obtained concentrate to obtain hydroxymethylfurfural. It is characterized by having a means for heat-concentrating the juice squeezed using a squeezing means for squeezing the fruit juice or for heat-concentrating honey, and a means for drying the obtained concentrate to obtain hydroxymethylfurfural. Hydroxymethylfurfural production equipment.

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