Preparation method and application of polyaspartic acid chelated zinc

Abstract

The invention discloses a preparation method and application of polyaspartic acid chelated zinc, which comprises: dissolving sodium hydroxide or potassium hydroxide in deionized water, dripping ammonia water and fully mixing, adding polysuccinimide, stirring and dissolving, and filtering to obtain a sodium polyaspartic acid / ammonium copolymer or a potassium polyaspartic acid / ammonium copolymer aqueous solution; using an inorganic acid aqueous solution to adjust the pH of the sodium polyaspartic acid / ammonium copolymer aqueous solution or the potassium polyaspartic acid / ammonium copolymer aqueous solution to 4.5-6.5, adding a water-soluble zinc salt, and continuously and fully stirring in a water bath to obtain a product solution; removing soluble impurities in the product solution to obtain a final product polyaspartic acid chelated zinc aqueous solution. The polyaspartic acid chelated zinc prepared by the method has a high zinc chelation rate, few free zinc ions, mild reaction conditions, and a simple method.

Description

Technical Field

[0001] The present invention relates to the technical field of daily chemical products, and particularly relates to a preparation method and application of zinc chelated with polyaspartic acid. Background Art

[0002] Zinc is one of the essential trace elements in the human body and plays an extremely important role in the growth and development process of the human body. Its content in the human body is second only to iron. In skin care, zinc can be beneficial to improving acne. It can maintain the functions of macrophages, neutrophils, and natural killer cells and the activity of complement by participating in histone deacetylation, and can stabilize the organelle membrane and reduce the production of inflammatory mediators; zinc can also block ultraviolet rays, has an antioxidant effect, and can promote the absorption of antibiotics.

[0003] Polyaspartic acid and its sodium salt show excellent moisturizing performance. In addition, it has a powerful water replenishing function to improve the skin moisture content; it has a high-efficiency water locking and moisturizing function, making the skin feel smooth and fresh. It can also supplement skin nutrition and improve the fullness and elasticity of the skin.

[0004] Therefore, zinc chelated with polyaspartic acid can increase the anti-inflammatory and whitening effects on the basis of the moisturizing property of polyaspartic acid and its sodium salt; and compared with elemental zinc, zinc oxide, and zinc salts, the relative stability of its chelation bond effectively improves the persistence of its efficacy.

[0005] Existing zinc chelated with polyaspartic acid is mostly used in feed or fertilizers, which is obtained through multiple-step reactions using zinc oxide or zinc hydroxide as raw materials. These processes have many control factors, relatively harsh conditions, and a relatively low chelation rate of zinc in the product. Therefore, it is necessary to develop a preparation process of zinc chelated with polyaspartic acid that is simple in preparation process, has fewer steps, and has a higher chelation rate of zinc in the product to meet the requirements as a cosmetic efficacy ingredient. Summary of the Invention

[0006] (1) Object of the Invention

[0007] The object of the present invention is to provide a preparation method and application of zinc chelated with polyaspartic acid. The zinc chelated with polyaspartic acid prepared by this method has a relatively high chelation rate of zinc and very few free zinc ions; the chelation process is a homogeneous reaction with water as a solvent, the reaction conditions are mild, and the method is simple, efficient, and environmentally friendly.

[0008] (2) Technical Solution

[0009] To solve the above problems, the first aspect of the present invention provides a preparation method of zinc chelated with polyaspartic acid, including:

[0010] S1. Dissolve sodium hydroxide or potassium hydroxide in deionized water, add ammonia water and mix well, then add polysuccinimide and stir to dissolve. After filtration, an aqueous solution of sodium / ammonium polyaspartate copolymer or an aqueous solution of potassium / ammonium polyaspartate copolymer is obtained;

[0011] S2. Using an aqueous solution of inorganic acid, adjust the pH of the aqueous solution of sodium / ammonium polyaspartate copolymer or the aqueous solution of potassium / ammonium polyaspartate copolymer to 4.5 - 6.5, then add a water-soluble zinc salt, and continuously stir well in a water bath at 60 - 80 °C to obtain a product solution;

[0012] S3. Separate and remove the soluble impurities in the product solution to obtain the final product, an aqueous solution of zinc chelated polyaspartate.

[0013] Further, in S1, the polysuccinimide is obtained by polymerizing aspartic acid, and the average molecular weight range of the polysuccinimide is 3 - 50 kDa.

[0014] Further, in S1, the molar ratio among ammonia water, sodium hydroxide or potassium hydroxide, and the repeating unit of polysuccinimide is x:1:y, where 0.05 ≤ x ≤ 0.2 and 0.8 ≤ y ≤ 1, and the polysuccinimide is composed of repeating units of polysuccinimide.

[0015] Further, in S1, the mass fraction of the aqueous solution of sodium / ammonium polyaspartate copolymer or the aqueous solution of potassium / ammonium polyaspartate copolymer is 3wt% - 30wt%.

[0016] Further, the method for separating and removing the soluble impurities in the product solution in S3 includes membrane filtration and electrodialysis.

[0017] Further, the water-soluble zinc salt includes zinc chloride, zinc sulfate, zinc nitrate, zinc acetate, zinc lactate, zinc gluconate, and zinc aspartate.

[0018] Further, in S2, the molar ratio between zinc in the water-soluble zinc salt and the repeating unit of sodium / ammonium polyaspartate or the repeating unit of potassium / ammonium polyaspartate is p:1, where 0.01 ≤ p ≤ 0.1.

[0019] Further, in the final product, the aqueous solution of zinc chelated polyaspartate, the soluble solid content is 5wt% - 30wt%.

[0020] Further, the mass fraction of zinc in the soluble solid content is 0.01wt% - 5wt%, and the free zinc content in the aqueous solution of zinc chelated polyaspartate does not exceed 1% of the mass fraction of zinc.

[0021] Another aspect of the present invention provides a cosmetic composition, which comprises an aqueous solution of zinc polyaspartate chelate as described in any one of the above descriptions.

[0022] (III) Beneficial effects

[0023] The present invention provides a preparation method and application of zinc polyaspartate chelate. In this preparation method, an aqueous solution of sodium / potassium polyaspartate / ammonium copolymer or potassium / ammonium polyaspartate copolymer is prepared with sodium hydroxide or potassium hydroxide, ammonia water, and polysuccinimide. Then, after adjusting the pH of the above solution to 4.5 - 6.5 with an aqueous solution of inorganic acid, a water-soluble zinc salt is added, and continuous and sufficient stirring is carried out in a water bath at 60 - 80 °C. The resulting solution is filtered to obtain the final product, an aqueous solution of zinc polyaspartate chelate. Compared with the production process using zinc oxide or zinc hydroxide as raw materials, the preparation method of the present invention is a homogeneous reaction with water as the solvent and has no exothermic process of acid-base neutralization. The process is simple, the conditions are mild, and the cost difference is small. The zinc polyaspartate chelate obtained by the preparation method of the present invention has a chelation rate of more than 99% based on zinc element, and there are very few free zinc ions, which is suitable for use as an active ingredient in cosmetics. The zinc polyaspartate chelate prepared by the present invention can effectively exert its effects in moisturizing, whitening, oil control, and anti-inflammation when applied in cosmetics. Description of the drawings

[0024] Figure 1 is a schematic diagram of the molecular structure of zinc polyaspartate chelate of the present invention;

[0025] Figure 2 is a schematic diagram of the reaction process in step S1 in a specific embodiment of the present invention;

[0026] Figure 3 Schematic diagram of the reaction process in step S2 in a specific embodiment of the present invention;

[0027] Figure 4 is the ultraviolet / visible light full-wavelength scanning spectrum of the product obtained in Example 6 of the present invention.

[0028] Figure 5 Infrared spectrum of the product obtained in Example 6 of the present invention;

[0029] Figure 6 is the thermogravimetric analysis of the product obtained by the method of Example 6 of the present invention;

[0030] Reference numerals in the drawings:

[0031] 1. Zinc sulfate; 2. Zinc lactate; 3. Sodium polyaspartate; 4. Zinc polyaspartate chelate; 5. Sodium polyaspartate; 6. Zinc polyaspartate chelate; 7. TG - Sodium polyaspartate; 8. TG - Zinc polyaspartate chelate; 9. DTG - Sodium polyaspartate; 10. DTG - Zinc polyaspartate chelate. Detailed implementation manners

[0032] To make the objectives, technical solutions and advantages of the present invention clearer and more understandable, the present invention will be further described in detail below in conjunction with the specific implementation manners and with reference to the accompanying drawings. It should be understood that these descriptions are merely exemplary and are not intended to limit the scope of the present invention. In addition, in the following descriptions, the descriptions of well - known structures and technologies are omitted to avoid unnecessarily confusing the concepts of the present invention.

[0033] When a numerical range is provided, it should be understood that each intermediate value between the upper and lower limits of the range and any other specified or intermediate value in the specified range is encompassed within the present invention. The upper and lower limits of these smaller ranges can be independently included in the smaller ranges and are also encompassed within the present invention, subject to any explicitly excluded limits in the specified range. When the specified range includes one or both of the limits, ranges excluding either or both of the included limits are also included in the present invention.

[0034] For any numerical value mentioned in the present invention, if there is only a two - unit interval between any lowest value and any highest value, all values increasing by one unit each from the lowest value to the highest value are included. For example, if the amount of a component, or the value of a process variable such as temperature, time, etc. is stated as 3 - 40, it means in this specification that 4 - 39, 5 - 38... as well as 20 - 23 and 21 - 24 etc. are specifically listed. For non - integer values, appropriate consideration can be given with 0.1, 0.01, 0.001 or 0.0001 as a unit. These are only some specifically indicated examples. In this application, in a similar manner, all possible combinations of the numerical values between the listed lowest and highest values are considered to have been disclosed.

[0035] Unless otherwise defined, all terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the present invention pertains. Although any methods and materials similar or equivalent to those described herein can also be used in the implementation or testing of the present invention, the preferred methods and materials are now described.

[0036] I. Terms

[0037] The term "water" used in the present invention, unless otherwise specified, refers to deionized water, ultrapure water or distilled water.

[0038] In the present invention, the terms "polyaspartic acid", "polytartaric acid", and "polymalic acid" have the same meaning, and the terms "zinc chelate of polyaspartic acid", "zinc chelate of polycondensed aspartic acid", and "zinc chelate of polymalic acid" can also be used interchangeably.

[0039] II. Detection Instruments and Methods

[0040] In the present invention, the pH value is measured using a SevenDirect SD20 from Mettler Toledo. The soluble solid content is measured using a PAL-1 from ATAGO. The total zinc content and the free zinc ion content are determined by atomic absorption spectrophotometry and EDTA titration respectively according to the group standard T / CFIAS6007-2024. The present invention analyzes and compares the efficacy of the zinc chelate of polyaspartic acid by means of cell experiments. III. Specific Embodiments

[0042] On the one hand, the present invention provides a method for preparing a zinc chelate of polyaspartic acid, comprising:

[0043] S1, dissolving sodium hydroxide or potassium hydroxide in deionized water, adding ammonia water and mixing thoroughly, then adding polysuccinimide (PSI), continuously stirring and dissolving sufficiently, and obtaining an aqueous solution of sodium / ammonium polyaspartate copolymer (PASPNa / NH 4 ) or an aqueous solution of potassium / ammonium polyaspartate copolymer (PASPK / NH 4 ) after filtration;

[0044] S2, adjusting the pH of the aqueous solution of PASPNa / NH 4 or the aqueous solution of PASPK / NH 4 to 4.5 - 6.5 with an aqueous solution of inorganic acid, adding a water-soluble zinc salt, and continuously stirring sufficiently in a water bath at 60 - 80 °C for 1 - 3 h to obtain a product solution;

[0045] S3, separating and removing the soluble impurities in the product solution to obtain a colorless or light yellow final aqueous solution of zinc chelate of polyaspartic acid.

[0046] Further, in S1, the PSI is polymerized from aspartic acid, and the average molecular weight range of the PSI is 3 - 50 kDa.

[0047] Further, in S1, the molar ratio among the ammonia water (NH 3 ) in the ammonia water, the sodium hydroxide or potassium hydroxide, and the polysuccinimide repeating unit is x:1:y, where 0.05 ≤ x ≤ 0.2 and 0.8 ≤ y ≤ 1, and the polysuccinimide is composed of polysuccinimide repeating units.

[0048] Further, in S1, the PASPNa / NH 4 or PASPK / NH 4 aqueous solution can be optionally diluted with deionized water or not, where the mass fraction of PASPNa / NH 4 or PASPK / NH 4 is 3 wt% to 30 wt%.

[0049] Further, in S1, the mass ratio of the deionized water to the PSI is k:1, where 2.5 ≤ k ≤ 5.

[0050] Further, the concentration of hydrogen ions in the inorganic acid aqueous solution is 1 mol / L, and the inorganic acid includes one or more of hydrochloric acid, sulfuric acid, phosphoric acid, and nitric acid.

[0051] Further, in S2, the molar ratio between zinc in the water-soluble zinc salt, the sodium / ammonium polyaspartate repeat unit, or the potassium / ammonium polyaspartate repeat unit is p:1, where 0.01 ≤ p ≤ 0.1, and the water-soluble zinc salt includes zinc chloride, zinc sulfate, zinc nitrate, zinc acetate, zinc lactate, zinc gluconate, and zinc aspartate.

[0052] Further, in the final product of the zinc chelate of polyaspartic acid aqueous solution, the soluble solid content is 5 wt% to 30 wt%.

[0053] Further, the mass fraction of zinc in the soluble solid content is 0.01 wt% to 5 wt%, and the free zinc content in the zinc chelate of polyaspartic acid aqueous solution does not exceed 1% of the mass fraction of zinc. The molecular structure of the product zinc chelate of polyaspartic acid is shown in Figure 1 , and the reaction process of step S1 is shown in Figure 2 , and the reaction process of step S2 is shown in Figure 3 .

[0054] Further, the method for separating and removing soluble impurities from the product solution in S3 includes membrane filtration and electrodialysis.

[0055] On the other hand, the present invention also provides a cosmetic composition, which includes the zinc chelate of polyaspartic acid aqueous solution as described in any one of the above claims, and the cosmetic composition includes preparations for facial masks, hand care products, sunscreen products, skin revitalizing products, antifreeze products, antidandruff products, moisturizing products, anti-inflammatory products, whitening products, and products for whitening and reducing melanin pigmentation.

[0056] The above solution will be described in detail below in combination with specific embodiments. For specific experimental methods not mentioned in the following examples, they are usually carried out according to conventional experimental methods. The raw materials or components used in the present invention can be obtained through commercial channels or conventional methods without special instructions.

[0057] Example 1 Preparation of Zinc Chelate of Polyaspartic Acid

[0058] Accurately measured deionized water was added to a 50 mL beaker, and then accurately weighed NaOH was added thereto; after fully stirring to completely dissolve NaOH, accurately weighed ammonia water was added, and the mixture was stirred evenly at room temperature; then accurately weighed PSI was added to the above mixed solution, and after reacting at room temperature with stirring for 2 h, the insoluble substances were removed by filtration to obtain an aqueous solution of PASPNa / NH 4 aqueous solution.

[0059] After adjusting the pH of the above aqueous solution of PASPNa / NH 4 with 1 mol / L hydrochloric acid aqueous solution, accurately weighed zinc salt was added; then, it was continuously stirred sufficiently at 60 °C in a water bath for 3 h to obtain a light yellow solution. After the above light yellow solution was filtered and separated through a filter membrane with a molecular weight cut-off of 3 kDa (compensating for the loss of the reaction system with deionized water based on the mass of the filtrate), a zinc chelate of polyaspartic acid solution was obtained. The specific process parameters and product indexes in the above process are shown in Table 1 and Table 2 (replacing NaOH with KOH in Example 1, and the steps and calculation processes are the same).

[0060] In addition, the preparation processes of Examples 2 - 19 are the same as those of Example 1, and the specific process parameters are shown in Table 1 in detail. Table 2 shows the product detection results corresponding to each example in Table 1.

[0061] Table 1 Preparation Process Parameters of Zinc Chelate of Polyaspartic Acid

[0062]

[0063]

[0064] Table 2 Detection Results of Each Example

[0065]

[0066] As can be seen from Table 2, membrane filtration can more thoroughly remove free zinc ions that have not formed a chelate structure.

[0067] Combined with Table 1 and Table 2, it can be seen from the comparison of Example 1, Example 6 and Example 19 that the average molecular weight of the raw material poly(succinimide) PSI (abbreviated as PSI molecular weight) will affect the soluble solids and zinc content of the product. That is, the lower the molecular weight of PSI prepared by the process, the higher the content of small molecule substances, the more soluble solids lost after passing through the filter membrane, and the more zinc content chelated with PASP is also lost. See Example 1 (this principle involves the production process of PSI. In the production of PSI, temperature, time, and catalyst dosage will all affect the molecular weight of the product PSI. Among them, low temperature, short time, and less catalyst dosage will result in a low molecular weight of the product PSI, but at the same time, the reaction rate will be low, that is, there are more small molecule substances; vice versa. The production process of PSI has been publicly reported); when the PSI molecular weight is too high, due to the steric hindrance of molecular chain entanglement, the formed chelation structure will also be relatively less. See Example 19. In the present invention, the average molecular weight range of PSI is 3 - 50 kDa, preferably 20 kDa. See Example 6.

[0068] Combined with Example 2, 4 and Example 3, 5, it can be seen that the addition amount of NaOH within a suitable range has little effect on the soluble solids and zinc content of the product, but too little (Example 3) will cause incomplete hydrolysis of PSI to form insoluble substances, resulting in a decrease in the soluble solids content, while too much addition of NaOH (Example 2) will increase the treatment pressure of membrane filtration.

[0069] Combined with Experimental Examples 4, 5, 6, it can be seen that the increase of ammonia can increase the content of PASN in the polymer, which is beneficial to the formation of chelated zinc structure within a suitable range. However, excessive addition of ammonia water (Example 5) will cause a decrease in pH during the hydrolysis of PSI to form insoluble substances, resulting in a decrease in the soluble solids content.

[0070] From the above comparison, it can be known that the molar ratio of the ammonia water (NH 3 ) in the ammonia water, the sodium hydroxide or potassium hydroxide, and the repeating unit formed by the poly(succinimide) is x:1:y (0.05 - 0.2:1:0.8 - 1), where 0.05 ≤ x ≤ 0.2 and 0.8 ≤ y ≤ 1. The following takes Example 6 as an example to illustrate the molar relationship among ammonia water, sodium hydroxide and the PSI repeating unit. The calculation process is as follows:

[0071] The concentration of ammonia water is 25%, and the molecular weight of ammonia water is 35. Therefore, the molar amount of ammonia water (calculated as NH 3 H 2 O) is 52.87×0.25 / 35 = 0.3776 mol;

[0072] The molar amount of sodium hydroxide is: 137.46 / 40 = 3.4365 mol;

[0073] The molar amount of the PSI repeating unit is as follows: The molecular weight of aspartic acid is 133. The PSI repeating unit is the product of aspartic acid removing 2 molecules of water, and its molecular weight is 97. Therefore, the molar amount of PSI is 300 / 97 = 3.0928 mol;

[0074] Therefore, the molar ratio among ammonia water, sodium hydroxide, and the PSI repeating unit is 0.11:1:0.89; the calculation process for other examples is the same.

[0075] Combined with Examples 6 to 9, it can be seen that as the addition amount of zinc salt increases within a suitable range, the zinc content of the product will increase accordingly; however, limited by the number of chelated zinc structures that the PASP / PASN system can accommodate, the zinc salt cannot be increased infinitely. Excessive zinc salt will not be chelated and will exist in a free state and be removed by membrane filtration. A far excessive amount of zinc salt will also form insoluble substances, as shown in Example 9 (Example 9 is the upper limit of the addition amount of zinc salt. This example proves that after the addition amount of zinc salt reaches a certain level, increasing the addition amount of zinc salt further cannot increase the number of chelated zinc, but the excess zinc will exist in the form of free zinc and be removed during the membrane filtration process).

[0076] Combined with Examples 6, 10 to 15, it can be seen that due to the strong chelating performance of PASP, generally soluble zinc salts can form chelated structures with PASP / PASN; among zinc salts, factors such as whether the anion is an organic or inorganic ion, the size of the anion, and the solubility of the zinc salt will have some influence on the zinc content, but the influence is not significant. The molar ratio of zinc, the PASPNa / NH 4 repeating unit or the PASPK / NH 4 repeating unit in is p:1, where 0.01 ≤ p ≤ 0.1. Here, the PASPNa / NH 4 repeating unit or the PASPK / NH 4 repeating unit molar amount is equal to the molar amount of the PSI repeating unit. The principle is as follows: Polysuccinimide is hydrolyzed under alkaline conditions to obtain polyaspartate. That is, polysuccinimide is hydrolyzed in an aqueous sodium hydroxide solution to obtain sodium polyaspartate; the same is true for potassium hydroxide. Therefore, the repeating unit of polysuccinimide is succinimide, and the repeating unit of sodium polyaspartate is aspartic acid. For the same polymer chain (i.e., polymer molecule), the number of repeating units of polysuccinimide and sodium polyaspartate remains unchanged before and after hydrolysis; that is, although the polymer structure changes before and after hydrolysis, the number of moles of the repeating unit remains unchanged. Therefore, the "molar ratio between zinc and the polyaspartate sodium / ammonium repeating unit or the polyaspartate potassium / ammonium repeating unit" is equal to the "molar ratio between zinc and the PSI repeating unit".

[0077] Taking Example 6 as an example, the molar relationship between zinc (Zn) and the PASPNa / NH 4 repeating unit is as follows:

[0078] The molecular weight of zinc sulfate is generally simply calculated as 161, so the molar amount is 17.43 / 161 = 0.1083 mol.

[0079] The molar ratio of Zn to PASPNa / NH 4 is 0.1083:3.0928, that is, 0.035:1. The calculation process for other examples is the same.

[0080] Combined with Examples 6 and 16, it can be seen that after increasing the amount of water added and reducing the reaction system concentration, in addition to the inevitable decrease in soluble solids, the zinc content also significantly decreases. The mass ratio of the deionized water to the polysuccinimide is k:1, where 2.5 ≤ k ≤ 5.

[0081] Taking Example 6 as an example, the amount of water added is 860.3 mL (calculated based on the density of deionized water being 1.0 g / mL, the added amount is 860.3 g), and its mass ratio to PSI is 2.87:1. The calculation process for other examples is the same.

[0082] In addition, combined with Examples 6, 17, and 18, it can be seen that the pH of the reaction system has a great influence on the zinc content. Too large (Example 18) or too small pH value (Example 17) will significantly reduce the zinc content in the product. From the results, the pH value is the most important influencing factor, and finally it is determined that the pH is adjusted to 4.5 - 6.5.

[0083] In step S1 of the present invention, PASPNa / NH is formed 4 with a mass fraction of 3 wt% - 30 wt% (if NaOH is replaced with KOH, the mass fraction of PASPK / NH 4 is 3 wt% - 30 wt%). Taking Example 6 as an example, the calculation process of the mass fraction of PASPNa / NH 4 is as follows:

[0084] The molecular weight of the repeating unit of PASPNa / NH 4 is 96, and the number of moles of the repeating unit of PASPNa / NH 4 is also 3.0928 mol, and the mass of water is 860.3 g.

[0085] The mass fraction of PASPNa / NH 4 = 96×3.0928 / (96×3.0928 + 860.3) ×

[0086] 100% = 25.7 wt%. The calculation for other examples is the same.

[0087] In the final product of zinc chelated polyaspartic acid aqueous solution prepared by the present invention, the soluble solids content is 5 wt% - 30 wt%, and the preferred content is 5 wt% - 25 wt%;

[0088] The mass fraction of zinc in the soluble solid content is 0.01 wt% to 5 wt%, preferably 0.05 wt% to 1 wt%.

[0089] The free zinc content in the aqueous solution of polyaspartic acid chelated zinc does not exceed 1% of the mass fraction of zinc.

[0090] The chelation rate of the polyaspartic acid chelated zinc obtained by the preparation method of the present invention, calculated based on zinc element, exceeds 99%. There are very few free zinc ions. The process is simple, the conditions are mild, and the cost difference is small.

[0091] UV / visible light full-wavelength scanning, infrared, and thermogravimetric analyses were performed on the product of Example 6. The results are shown in Figure 4 , Figure 5 and Figure 6 . Among them, from Figure 4 the UV / visible light full-wavelength scanning results (the upper right corner is the enlarged UV image of polyaspartic acid chelated zinc and sodium polyaspartate), compared with the maximum absorption peak of sodium polyaspartate at 230 nm (label 3), polyaspartic acid chelated zinc (label 4) has an additional absorption peak at 219 nm. From this figure, it can be seen that sodium polyaspartate alone has one and only one maximum absorption peak at around 230 nm in the UV wavelength; while the product of the present invention, in addition to sodium polyaspartate, also has a chelated zinc structure, and this chelated structure has a UV absorption peak at 219 nm in the UV wavelength. Therefore, the UV full-wavelength scanning spectrum can qualitatively prove that through the chelation reaction, a new compound different from the original sodium / ammonium polyaspartate is obtained, and based on the reaction conditions, it is determined to be polyaspartic acid chelated zinc), Figure 4 where the abscissa is wavelength (Wavelength) in nm and the ordinate is absorbance (ABs). The changes in the vibration peaks on the infrared spectrum are shown in Table 3. The amide bond on the main chain of polyaspartic acid and the carboxyl group on the side chain, the stretching vibration peaks of acyl groups, amino groups, etc. in their infrared spectra will inevitably cause changes in the absorption peak positions after chelation with zinc ions. As Figure 5 and Table 3 show, comparing the infrared spectrum of polyaspartic acid chelated zinc (label 6) with that of sodium polyaspartate (label 5), it is found that after the chelation reaction, the position of the C=O stretching vibration peak shifts and splits into two peaks, the C-O stretching vibration peak significantly redshifts, the absorption peak representing COOH has a small displacement but a significant decrease in intensity, indicating that a large number of carboxyl groups participate in the chelated structure; the absorption peaks of N-H, C-H, and C-N bonds also shift to varying degrees, indicating that zinc atoms form a chelated structure with polyaspartic acid and affect the stretching vibration of chemical bonds of its surrounding groups. Similar to the Figure 4 UV full-wavelength scanning spectrum,[[]] Figure 5The infrared spectrum is also a qualitative analysis of the chelation structure of polyaspartic acid. That is, compared with sodium polyaspartate, the position of the vibration peak related to the carboxyl group shifts, indicating that the carboxyl group participates in the zinc chelation structure and simultaneously qualitatively proves the formation of the chelated zinc structure. Figure 5 In Figure 5 , the abscissa is the wavenumber, with the unit of cm -1 , and the ordinate is the transmittance.

[0092] Table 3 Changes in vibration peaks in the infrared spectrum

[0093]

[0094] From Figure 6 In the thermogravimetric analysis diagram, it can be seen that during the continuous heating of sodium polyaspartate, as shown by curve 7, first, the mass slowly decreases with the volatilization of bound water at 100 °C - 300 °C, and at around 300 °C, the mass decreases sharply with the decarboxylation and dehydration of the side-chain carboxyl groups, and at around 400 °C, the amide bond breaks, the carbon chain rearranges, and CO 2 , H 2 O, NH 3 and other small-molecule substances are released, resulting in a decrease in mass. Due to the chelation structure of polyaspartic acid chelated zinc, as shown by curve 8, it can appropriately improve the thermal stability of the polymer similar to a cross-linking agent. Therefore, the mass loss of polyaspartic acid chelated zinc at around 300 °C is lower than that of sodium polyaspartate, and at around 350 °C, there will be an additional mass loss stage with the disintegration of the chelation structure accompanied by decarboxylation and dehydration. Figure 6 In Figure 6 , TG is the thermogravimetric curve and DTG is the differential thermogravimetric curve. The thermogravimetric analysis results of this figure prove that during the continuous increase in temperature, the mass loss degree and loss rate of the product of the present invention are different from those of sodium polyaspartate; that is, there are obvious structural differences in the present invention compared with the raw material sodium polyaspartate / ammonium.

[0095] Based on the comprehensive analysis results of ultraviolet, infrared, and thermogravimetry, it can be qualitatively considered that the product of the present invention has a new structure significantly different from the original sodium polyaspartate / ammonium; and through the reaction process judgment, there is a relatively stable chelated zinc structure in the product of the present invention.

[0096] IV. Scale-up of the preparation process

[0097] Based on the process conditions of Example 6 above, the industrial preparation of polyaspartic acid chelated zinc is carried out. The specific method is as follows: Add 34.4 L of deionized water to a 70 L reaction tank, and slowly add 5.50 kg of NaOH thereto with stirring. After complete dissolution, add 2.12 kg of ammonia water and stir well and mix evenly. After the mixed solution returns to room temperature, slowly add 12 kg of PSI with stirring and continue stirring for 2 h to obtain PASPNa / NH4 aqueous solution. After removing insolubles from the above PASPNa / NH 4 aqueous solution through a pipeline filter, adjust its pH to 6.0 with 1 mol / L hydrochloric acid aqueous solution, and then slowly add 0.70 kg of zinc sulfate. After the addition of zinc sulfate is completed, heat the reaction tank to 60 °C and stir thoroughly for 3 h. After the reaction ends, wait for the system to cool naturally to room temperature, and filter through a filter membrane with a pore size of 3000 to obtain the product zinc polyaspartate chelate solution (make up for the loss of the reaction system with deionized water based on the mass of the filtrate). The color of this product is light yellow, with a total of 49.84 kg; the soluble solid content is 24.44 wt%, the total zinc content is 0.47 wt%, and free zinc is not detected.

[0098] It can be seen from the scale-up experiment that the preparation process described in the present invention meets the conditions for industrial production.

[0099] V. Efficacy Evaluation

[0100] 1. Anti-inflammatory Efficacy Evaluation (Hyaluronidase Inhibition Rate)

[0101] Hyaluronidase is a participant in type I allergic reactions. There is a strong correlation between hyaluronidase and inflammation and allergies. Research reports that various drugs that release histamine from mast cells can regulate the activity of hyaluronidase, and some anti-allergic drugs have strong inhibitory effects on the activity of hyaluronidase. Therefore, inhibiting the activity of hyaluronidase is used as an index for studying anti-inflammatory effects.

[0102] Test the hyaluronidase inhibition rate of the zinc polyaspartate chelate prepared in the present invention. The test method includes:

[0103] (1) Prepare the test solutions according to the components shown in Table 4.

[0104] Table 4 Components of the Test Solutions

[0105]

[0106] (2) After incubating the solutions obtained in the above step (1) at 37 °C for 20 min, add 0.1 mL of 2.5 mol / L CaCl 2 solution to each solution; continue to incubate at 37 °C for 20 min, then add 0.5 mL of 0.5 mg / ml sodium hyaluronate solution to solutions A and C respectively, and add 0.5 mL of acetic acid buffer solution with pH = 5.6 to solutions B and D respectively.

[0107] (3) After keeping the solutions obtained in the above step (2) at 37 °C for another 40 min, place them at room temperature (25 °C) for 10 min, and respectively add 0.5 mL of pure water and 0.1 mL of 5 mol / L NaOH solution dropwise; at the same time, 0.5 mL of the mixed solution should also be added dropwise. The preparation process of the mixed solution is as follows: Mix 50 ml of 10 mol / L sodium carbonate solution and 3.5 ml of acetylacetone evenly to form a mixed solution.

[0108] (4) Place the solutions obtained in the above step (3) in a boiling water bath for 15 min respectively, then place them in an ice bath for 10 min, and then let them stand at room temperature (25 °C) for 10 min; Dissolve 0.8 g of p-dimethylaminobenzaldehyde in 15 ml of concentrated hydrochloric acid and 15 ml of absolute ethanol to prepare the P-DAB color reagent; Add 1 mL of the P-DAB color reagent to each of the solutions obtained in the above step (3) respectively.

[0109] (5) After shaking the solutions obtained in the above step (4) thoroughly, supplement the solution volume to 8 mL with absolute ethanol; Let it stand at room temperature (25 °C) for 30 min, and then measure the absorbance at 530 nm with a UV spectrophotometer.

[0110] The calculation method of the hyaluronidase inhibition rate is as follows:

[0111]

[0112] Where: A is the UV absorption value of solution A (i.e., the mixed solution of the sample, hyaluronidase and sodium hyaluronate); B is the UV absorption value of solution B (i.e., the mixed solution of the sample and acetate buffer); C is the UV absorption value of solution C (i.e., the mixed solution of hyaluronidase and sodium hyaluronate); D is the UV absorption value of solution D (i.e., acetate buffer).

[0113] Detect the hyaluronidase inhibition rate according to the above method. Use the products obtained in Examples 6, 7, 9, and 13 diluted 20 times as samples, use 1 wt% sodium polyaspartate (molecular weight 8 kDa) aqueous solution and 2.48 wt% zinc sulfate aqueous solution as controls, and use acetate buffer as the blank. The results are shown in Table 5.

[0114] Table 5 Detection results of hyaluronidase inhibition rate

[0115]

[0116] As shown in Table 5, all sample solutions have the effect of inhibiting hyaluronidase. Among them, with the increase of the content of chelated zinc, the inhibition rate of hyaluronidase shows an upward trend, but there is no linear relationship between the two; when the zinc content increases to a limit value, the increase of the inhibition rate of hyaluronidase will slow down. At the same time, the inhibition rate of hyaluronidase is not significantly affected by the type of zinc salt added in the process. In addition, the inhibition rate of hyaluronidase of polyaspartic acid chelated zinc is significantly higher than that of sodium polyaspartate, indicating that zinc element has an obvious promoting effect; and the inhibition rate of hyaluronidase of chelated zinc is higher than that of free zinc ions, indicating that the chelation structure can improve the utilization rate of zinc element. From the above, it can be seen that polyaspartic acid chelated zinc has an obvious effect on improving the inhibition rate of hyaluronidase and has good anti-inflammatory efficacy.

[0117] 2. Evaluation of Whitening Efficacy (Tyrosinase Inhibition Rate)

[0118] Tyrosinase is the rate-limiting enzyme in the process of melanin synthesis. The depth of human epidermal pigment and pigmentation diseases are all related to the activity of tyrosinase in the body. The greater the activity and the higher the content, the easier it is to form melanin. In the metabolic process, L-tyrosine can be converted into dopa under the action of tyrosinase, and dopa will be further catalyzed by tyrosinase to generate dopaquinone. Since dopaquinone has the maximum absorption peak at a wavelength of 475 nm, the inhibitory efficiency of the sample on tyrosine can be characterized by measuring the absorbance of the product dopaquinone, and its whitening effect can be proved.

[0119] The test method for the whitening effect of polyaspartic acid chelated zinc includes:

[0120] (1) Prepare the solution to be tested according to the components shown in Table 6.

[0121] Table 6 Ratio of Solution to be Tested

[0122]

[0123] (2) After heating and reacting the solutions in a water bath at 37 °C for 10 min, measure the absorbance at 475 nm with an ultraviolet spectrophotometer.

[0124] The calculation method of the tyrosinase inhibition rate is:

[0125]

[0126] Among them: C1 is the absorbance of the tyrosine solution; C2 is the absorbance of the mixed solution of tyrosinase and tyrosine; T1 is the absorbance of the sample to be tested and the tyrosine solution; T2 is the absorbance of the sample to be tested, tyrosinase and the mixed solution of tyrosine.

[0127] The tyrosinase inhibition rate was detected by the above method. The products obtained in Examples 6, 7, 9, and 13 were diluted 20 times as samples, 1 wt% aqueous solution of sodium polyaspartate (molecular weight 8 kDa) and 2.48 wt% aqueous solution of zinc sulfate were used as controls, and phosphate buffer was used as the blank. The results are shown in Table 7.

[0128] Table 7 Tyrosinase Inhibition Rate

[0129]

[0130] As shown in Table 7, all sample solutions had tyrosinase inhibition effects, and the inhibition pattern was similar to that of hyaluronidase mentioned above. Among them, with the increase of chelated zinc content, the tyrosinase inhibition rate showed an upward trend, but there was no linear relationship between them; when the zinc content increased to a certain limit, the increase of the tyrosinase inhibition rate would slow down. At the same time, the tyrosinase inhibition rate was not significantly affected by the type of zinc salt added in the process. In addition, the tyrosinase inhibition rate of zinc polyaspartate was significantly higher than that of sodium polyaspartate, indicating that zinc element had an obvious promoting effect; and the tyrosinase inhibition rate of chelated zinc was higher than that of free zinc ions, indicating that the chelated structure could improve the utilization rate of zinc element. From the above, it can be seen that zinc polyaspartate has an obvious effect on improving the tyrosinase inhibition rate and has good whitening efficacy.

[0131] 3. Evaluation of Oil Control Efficacy (5α-Reductase Inhibition Rate)

[0132] 5α-Reductase is a membrane protease dependent on reduced coenzyme II (NADPH) and is an important androgen metabolic enzyme in the skin. It can irreversibly convert testosterone into dihydrotestosterone, which is the most active androgen and can induce excessive sebum secretion by sebaceous glands. By inhibiting the activity of 5α-reductase to reduce the level of dihydrotestosterone, the excessive sebum secretion by sebaceous glands can be effectively alleviated. Therefore, inhibiting the activity of 5α-reductase was used as an index for studying the oil control effect.

[0133] The test method for the 5α-reductase inhibition rate of zinc polyaspartate includes:

[0134] (1) Take out the Omnimabs Human Steroid 5Alpha Reductase (SRD5a) kit and place it at room temperature (20 - 25 °C) for 30 min.

[0135] (2) Operate strictly according to the operation procedure of the kit, and finally measure the ultraviolet absorption at 450 nm.

[0136] (3) Obtain the content of 5α-reductase according to the standard curve and calculate the 5α-reductase inhibition rate.

[0137] The calculation method of the 5α-reductase inhibition rate is:

[0138]

[0139] Wherein: C is the content of 5α-reductase in the negative control; T is the content of 5α-reductase in the sample solution.

[0140] Detect the tyrosinase inhibition rate according to the above method. Using the products obtained from Experiments 6, 7, 9, and 13 in Example 1 diluted 20 times as samples, using an aqueous solution of 1 wt% sodium polyaspartate (molecular weight 8 kDa) and an aqueous solution of 2.48 wt% zinc sulfate as controls, using deionized water as the negative control, and using 0.5 μmol dutasteride as the positive control. The results are shown in Table 8.

[0141] Table 8 5α-Reductase Inhibition Rate

[0142]

[0143] As shown in Table 8, all sample solutions have an inhibitory effect on 5α-reductase, and the pattern is similar to that of the above hyaluronidase inhibition. Among them, as the content of chelated zinc increases, the 5α-reductase inhibition rate shows an upward trend, but there is no linear relationship between the two; when the zinc content increases to a limit value, the increase in the 5α-reductase inhibition rate will slow down. At the same time, the tyrosinase inhibition rate is not significantly affected by the type of zinc salt added in the process. In addition, the tyrosinase inhibition rate of zinc polyaspartate chelate is significantly higher than that of sodium polyaspartate, indicating that zinc element has an obvious promoting effect; and the tyrosinase inhibition rate of chelated zinc is higher than that of free zinc ions, indicating that the chelated structure can improve the utilization rate of zinc element. From the above, it can be seen that zinc polyaspartate chelate has an obvious effect on improving the 5α-reductase inhibition rate and has good oil control efficacy.

Claims

1. A method for preparing polyaspartic acid chelated zinc, characterized in that: include: S1, dissolving sodium hydroxide or potassium hydroxide in deionized water, adding ammonia water dropwise and mixing thoroughly, adding polysuccinimide, stirring to dissolve, and filtering to obtain a sodium polyaspartate / ammonium copolymer aqueous solution or a potassium polyaspartate / ammonium copolymer aqueous solution; the molar ratio of the ammonia water, the sodium hydroxide or potassium hydroxide, and the repeating unit of the polysuccinimide is x:1:y, wherein 0.05≤x≤0.2, 0.8≤y≤1, and the polysuccinimide is composed of polysuccinimide repeating units; S2, using an inorganic acid aqueous solution to adjust the pH of the sodium polyaspartate / ammonium copolymer aqueous solution or the potassium polyaspartate / ammonium copolymer aqueous solution to 4.5-6.5, adding a water-soluble zinc salt, and continuing to fully stir in a water bath at 60-80° C. to obtain a product solution; S3, separating and removing soluble impurities in the product solution to obtain a final product, a polyaspartate chelated zinc aqueous solution.

2. The method for preparing polyaspartate chelated zinc according to claim 1, characterized in that: In S1, the polysuccinimide is obtained by polymerization of aspartic acid, and the average molecular weight of the polysuccinimide is in the range of 3 to 50 kDa.

3. The method for preparing polyaspartate chelated zinc according to claim 1, characterized in that: In S1, the mass fraction of the sodium polyaspartate / ammonium copolymer aqueous solution or the potassium polyaspartate / ammonium copolymer aqueous solution is 3 wt % to 30 wt %.

4. The method for preparing polyaspartate chelated zinc according to claim 1, characterized in that: The method for separating and removing soluble impurities in the product solution in S3 includes membrane filtration and electrodialysis.

5. The method for preparing polyaspartate chelated zinc according to claim 1, characterized in that: The water-soluble zinc salts include zinc chloride, zinc sulfate, zinc nitrate, zinc acetate, zinc lactate, zinc gluconate and zinc aspartate.

6. The method for preparing polyaspartate chelated zinc according to claim 1, characterized in that: In S2, the molar ratio between zinc in the water-soluble zinc salt and the sodium / ammonium polyaspartate repeating unit or the potassium / ammonium polyaspartate repeating unit is p:1, wherein 0.01≤p≤0.

1.

7. The method for preparing polyaspartate chelated zinc according to claim 1, characterized in that: The final product, the polyaspartate chelated zinc aqueous solution, has a soluble solid content of 5 wt% to 30 wt%.

8. The method for preparing polyaspartate chelated zinc according to claim 7, characterized in that: The mass fraction of zinc in the soluble solid content is 0.01 wt % to 5 wt %, and the content of free zinc in the polyaspartic acid chelated zinc aqueous solution does not exceed 1 % of the mass fraction of zinc.

9. A cosmetic composition, characterized in that The cosmetic composition comprises the polyaspartate chelated zinc aqueous solution obtained by the preparation method of polyaspartate chelated zinc according to any one of claims 1 to 8.

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