Whitening composition containing PDRN and SOD enzyme

Abstract

The invention discloses a whitening composition containing PDRN and SOD (superoxide dismutase). The composition comprises a selaginella tamariscina extract, a mulberry root extract, a cystosella rubra extract and a nucleotide protein compound, and the nucleotide protein compound comprises the PDRN and the SOD. The composition obtained by scientific compatibility of the selaginella tamariscina extract, the mulberry root extract, the cystosella rubra extract and the nucleotide protein compound has a remarkable inhibition effect on tyrosinase activity, is safe and efficient, and can be widely applied to the field of cosmetics.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of cosmetics, in particular to a whitening composition containing PDRN and SOD enzyme. BACKGROUND

[0002] In recent years, with the increasing pursuit of skin whitening, developing efficient and safe tyrosinase inhibitors has become a research hotspot in the field of cosmetics. Tyrosinase, as the key enzyme in melanin synthesis, its activity directly affects the degree of skin pigmentation. However, the existing technology has the following limitations in inhibiting tyrosinase: Current commercially available whitening products rely on single active ingredients (such as arbutin, kojic acid, vitamin C derivatives, etc.), although they have certain inhibitory effects, but are easily affected by environmental factors (such as ultraviolet light, oxidative stress), and long-term use may lead to increased skin tolerance or damaged barrier function. For example, arbutin is easily decomposed and ineffective under strong light, while kojic acid may cause skin sensitivity.

[0003] The activity of tyrosinase is regulated by multiple dimensions, including gene transcription (such as MITF protein), enzyme protein modification (such as phosphorylation activation), cofactor binding (such as Cu²⁺ chelation), and substrate competition. The existing ingredients are mostly targeted at a single target (such as directly inhibiting enzyme activity or scavenging free radicals), which is difficult to achieve whole-cycle regulation, resulting in insufficient inhibition efficiency.

[0004] Although PDRN (polydeoxyribonucleotides) has been proven to promote cell proliferation and repair by activating A2A adenosine receptors, and SOD (superoxide dismutase) can enhance antioxidant capacity by scavenging superoxide anions, but the synergistic application of the two in the field of whitening has not been reported. When used alone, PDRN has weak tyrosinase inhibition effect, and SOD has limited direct inhibition effect, which needs to be complemented by composition design.

[0005] In view of the above problems, it is urgent to develop a whitening composition with multiple target synergies, safety, mildness and strong stability. By integrating natural plant extracts, functional nucleic acid ingredients (PDRN) and antioxidant enzymes (SOD), a complex system targeting whole-cycle regulation of tyrosinase is constructed to meet the urgent needs of the market for efficient and low-irritation whitening products. SUMMARY

[0006] Therefore, the purpose of the present application is to overcome the deficiencies of the prior art and provide a whitening composition containing PDRN and SOD enzyme.

[0007] To achieve the above purpose, the technical solution adopted by the present application is as follows: In a first aspect, the present application provides a whitening composition containing PDRN and SOD enzyme, which comprises the following components by mass fraction: Extract of Selaginella tamariscina: 2-4 parts; Extract of Morus root: 1-3 parts; Extract of Porphyridium: 8-10 parts; Nucleotide protein complex: 0.5-1.5 parts; The nucleotide protein complex comprises PDRN and SOD enzyme.

[0008] Preferably, the PDRN has an average molecular weight of 50-850 KDa; the SOD enzyme has an activity of 50,000-200,000 U / g.

[0009] Preferably, the mass ratio of PDRN to SOD enzyme in the nucleotide protein complex is 1:0.6-1.3.

[0010] In a second aspect, the present application provides use of the whitening composition containing PDRN and SOD enzyme in the first aspect in the preparation of a cosmetic product having whitening effect.

[0011] Preferably, the dosage form of the cosmetic product having whitening effect comprises any one of cream, emulsion, serum.

[0012] In a third aspect, the present application provides a serum having whitening effect, which comprises 0.1-5 wt% of the whitening composition containing PDRN and SOD enzyme in the first aspect.

[0013] Preferably, the serum having whitening effect further comprises a humectant, a preservative, a thickening agent, a pH regulator, deionized water.

[0014] Preferably, the humectant is at least one of sodium hyaluronate, glycerol, squalane.

[0015] Preferably, the preservative is at least one of p-hydroxyacetophenone, ethylhexylglycerin, caprylyl glycol.

[0016] Preferably, the thickening agent is at least one of xanthan gum, hydroxyethylcellulose, acryloyldimethyltaurine ammonium / VP copolymer, polyacryloyldimethyltaurate sodium.

[0017] Preferably, the pH regulator is tromethamine.

[0018] Compared with the prior art, the present application has the following beneficial effects: The whitening composition containing PDRN and SOD enzyme comprises the following components: eustigmatophyte extract, selaginella extract, mulberry root extract and nucleotide protein complex, wherein the nucleotide protein complex comprises PDRN and SOD enzyme; the above-mentioned five components realize synergistic effect through whole-cycle synergistic regulation in inhibiting tyrosinase, effectively inhibit tyrosinase activity, wherein the eustigmatophyte extract targets the activation of the key transcription factor MITF of tyrosinase, reduces the total amount of tyrosinase synthesis from the source; the selaginella extract blocks the downstream signal of MITF, inhibits the phosphorylation activation of the synthesized tyrosinase, and reduces its functional activity; the mulberry root extract is rich in polyphenols, which chelates copper ions of tyrosinase through catechol structure, deprives the catalytic center of tyrosinase and makes it inactivate; the enzymatic oligosaccharides in the eustigmatophyte extract and the flavonoids in the selaginella extract synergistically block the amino acid residue binding site of tyrosinase, prevent the substrate from entering, and double-block the catalytic function of the enzyme. The nucleotide protein complex (PDRN+SOD) further enhances the effect, PDRN activates the A2A adenosine receptor of melanocytes, promotes the target enrichment of other active ingredients (selaginella extract, mulberry bark extract, eustigmatophyte extract) in the composition to melanocytes; SOD catalyzes the conversion of superoxide anion, maintains the stability of the microenvironment, avoids the oxidation and destruction of other active substances in the composition, and ensures the persistence of the inhibition effect. The five components realize significant synergistic effect through whole-chain synergy of “reducing synthesis-inhibiting activation-chelating metal ions-blocking sites-enriching and stabilizing”. DETAILED DESCRIPTION

[0019] In order to better illustrate the purposes, technical solutions and advantages of the present application, the present application will be further described below in combination with specific examples. The purpose is to understand the content of the present application in detail, rather than to limit the present application. All other examples obtained by those of ordinary skill in the art without creative labor fall within the protection scope of the present application. The experimental reagents and instruments designed in the examples and comparative examples of the present application are common reagents and instruments unless otherwise specified, and can be obtained from commercial channels. In the examples and comparative examples, the experimental methods used are conventional methods unless otherwise specified; and the raw materials used in parallel experiments are the same batch of raw materials unless otherwise specified.

[0020] Further description of the raw materials used in the present application: The eustigmatophyte extract is purchased from CODIF TECHNOLOGIE NATURELLE, item number: CYBRIGHT.

[0021] The selaginella extract is purchased from Shanghai Gaikai Biological Co., Ltd., item number: Gerbex® Selaginella.

[0022] Mulberry root extract was purchased from Yunnan Inge Biotechnology Co., Ltd., item number: black ink.

[0023] PDRN was purchased from Boman Biotech (Shanghai) Co., Ltd., item number: RJMPDRN-850K, average molecular weight 850KDa; item number: RJMPDRN-C02, average molecular weight: 400KDa; item number: RJMPDRN-S02, average molecular weight: 50KDa.

[0024] SOD enzyme was purchased from Shenzhen Zhongkeyixian Biotechnology Co., Ltd., item number: O-SOD-200,000, enzyme activity: 200,000 U / g; item number: O-SOD-100,000, enzyme activity: 100,000 U / g; item number: O-SOD-50,000, enzyme activity: 50,000 U / g.

[0025] The remaining raw materials, reagents, etc. were all commercially available.

[0026] The whitening composition containing PDRN and SOD enzyme, its components, mass parts and preparation method are as follows: Composition 1: Selaginella extract: 3 parts; Mulberry root extract: 2 parts; Euglena gracilis extract: 9 parts; Nucleotide protein complex: 1 part; The nucleotide protein complex is composed of PDRN and SOD enzyme, wherein the mass ratio of PDRN to SOD enzyme is 1:0.8, the average molecular weight of PDRN is 50 KDa, and the SOD enzyme activity is 200,000 U / g.

[0027] Preparation method: mix Selaginella extract, mulberry root extract, Euglena gracilis extract and nucleotide protein complex uniformly, seal, and store at 5°C in the dark.

[0028] Composition 2: Selaginella extract: 2 parts; Mulberry root extract: 1 part; Euglena gracilis extract: 8 parts; Nucleotide protein complex: 0.5 parts; The nucleotide protein complex is composed of PDRN and SOD enzyme, wherein the mass ratio of PDRN to SOD enzyme is 1:0.6, the average molecular weight of PDRN is 400KDa, and the SOD enzyme activity is 50,000 U / g.

[0029] Preparation method: mix Selaginella extract, mulberry root extract, Euglena gracilis extract and nucleotide protein complex uniformly, seal, and store at 5°C in the dark.

[0030] Composition 3: Selaginella extract: 4 parts; Mulberry root extract: 3 parts; Euglena gracilis extract: 10 parts; Nucleotide protein complex: 1.5 parts; The nucleotide protein complex is composed of PDRN and SOD enzyme, wherein the mass ratio of PDRN to SOD enzyme is 1:1.3, the average molecular weight of PDRN is 850 KDa, and the activity of SOD enzyme is 100,000 U / g.

[0031] Preparation method: mix Selaginella extract, mulberry root extract, Euglena gracilis extract, and nucleotide protein complex uniformly, seal, and store at 5°C in the dark.

[0032] Composition ①: Different from composition 1, it lacks Selaginella extract, and the missing mass parts are supplemented with 2:9 mulberry root extract and Euglena gracilis extract, and the rest of the components and their mass parts are the same as composition 1. Preparation method: mix mulberry root extract, Euglena gracilis extract, and nucleotide protein complex uniformly, seal, and store at 5°C in the dark.

[0033] Composition ②: Different from composition 1, it lacks mulberry root extract, and the missing mass parts are supplemented with 3:9 Selaginella extract and Euglena gracilis extract, and the rest of the components and their mass parts are the same as composition 1. Preparation method: mix Selaginella extract, Euglena gracilis extract, and nucleotide protein complex uniformly, seal, and store at 5°C in the dark.

[0034] Composition ③: Different from composition 1, it lacks Euglena gracilis extract, and the missing mass parts are supplemented with 3:2 mulberry root extract and Selaginella extract, and the rest of the components and their mass parts are the same as composition 1. Preparation method: mix Selaginella extract, mulberry root extract, and nucleotide protein complex uniformly, seal, and store at 5°C in the dark.

[0035] Composition ④: Different from composition 1, PDRN with an average molecular weight of 50 KDa is used to replace the nucleotide protein complex in equal mass, and the rest of the components and their mass parts are the same as composition 1. Preparation method: mix Selaginella extract, mulberry root extract, Euglena gracilis extract, and PDRN uniformly, seal, and store at 5°C in the dark.

[0036] Composition ⑤: Different from composition 1, the nucleotide protein complex is replaced by SOD enzyme with equal mass, and the mass fraction of the rest of the components is the same as that of composition 1. Preparation method: mix the Selaginella moellendorfi extract, mulberry root extract, and euglena gracilis extract uniformly, seal, and store at 5°C in the dark.

[0037] Composition ⑥: Different from composition 1, the nucleotide protein complex is replaced by Selaginella moellendorfi extract, mulberry root extract, and euglena gracilis extract with a mass ratio of 3:2:9, and the mass fraction of the rest of the components is the same as that of composition 1. Preparation method: mix the Selaginella moellendorfi extract, mulberry root extract, and euglena gracilis extract uniformly, seal, and store at 5°C in the dark.

[0038] Composition ⑦: Different from composition 1, the Selaginella moellendorfi extract, mulberry root extract, and euglena gracilis extract are replaced by a nucleotide protein complex, and the mass fraction of the rest of the components is the same as that of composition 1. Preparation method: seal the nucleotide protein complex and store at 5°C in the dark.

[0039] Composition ⑧: Selaginella moellendorfi extract: 9 parts; Mulberry root extract: 1 part; Euglena gracilis extract: 3 parts; Nucleotide protein complex: 2 parts; The nucleotide protein complex is composed of PDRN and SOD enzyme, and the mass ratio of PDRN to SOD enzyme is 1:0.8, the average molecular weight of PDRN is 50 KDa, and the activity of SOD enzyme is 200,000 U / g.

[0040] The preparation method is the same as that of composition 1.

[0041] An essence with whitening effect, the components and mass percentages of which are shown in the following Table 1: Table 1 Components and mass percentages of essence with whitening effect

[0042] Note: "-" means not added; "appropriate amount" in the pH regulator means that the pH is adjusted to the specified pH, and the "specified pH" is the specified pH in the preparation steps of the essence.

[0043] The preparation method of the above-mentioned essence 1 is as follows: Step 1: Mix the composition, preservative, humectant and 1 / 2 deionized water at 25°C to obtain mixture A; Step 2: Mix the thickener with 1 / 4 deionized water at 40°C until homogeneous to obtain mixture B; Step 3: After mixture B cools to 25°C, mix mixture B with mixture A and the remaining deionized water evenly and adjust the pH to 6 using a pH adjuster to obtain the essence.

[0044] The preparation methods for serums 1-5 and serums ①-⑧ are the same as those for serum 1.

[0045] The preparation method for blank serum is as follows: Step 1: Mix the preservative, humectant and 1 / 2 deionized water at 25°C until homogeneous to obtain mixture A; Step 2: Mix the thickener with 1 / 4 deionized water at 40°C until homogeneous to obtain mixture B; Step 3: After mixture B cools to 25°C, mix mixture B with mixture A and the remaining deionized water evenly and adjust the pH to 6 using a pH adjuster to obtain the essence.

[0046] Experiment 1: Tyrosinase Inhibition Test Tyrosinase activity is related to melanin synthesis; inhibiting tyrosinase activity can reduce melanin production in the skin. This study evaluates the skin-whitening efficacy of the composition by its effect on tyrosinase activity.

[0047] Solvent preparation: PBS buffer: purchased from Solarbio; catalog number: P1039; L-Tyrosine solution: Dissolve L-tyrosine in PBS buffer to a final concentration of 0.5 mg / mL; Tyrosinase solution: Dissolve tyrosinase in PBS buffer to a final concentration of 500 U / mL; Sample solutions: Prepare 1wt% sample solutions of compositions 1-3 and compositions ①-⑧ using deionized water.

[0048] Test method: In 96-well microplates, samples were added according to the following groups: solvent background group, solvent reaction group and sample background group, and sample reaction group, with three replicates for each group. First, L-tyrosine solution, sample solution / deionized water, and PBS buffer were added to each well sequentially, mixed thoroughly, and incubated at 37°C in the dark for 10 min. Then, 20 μL of tyrosinase solution was added to each well sequentially, and the mixture was incubated at 37°C for 5 min ± 5 s. The absorbance was immediately measured at 475 nm using a microplate reader. The amounts added to each well are shown in Table 2 below. Table 2 Tyrosinase inhibition test amount per well Components Solvent background group (A) Solvent reaction group (B) Sample background group (C) Sample reaction group (D) L-tyrosine solution (μL) 0 40 0 40 Sample solution (μL) 0 0 40 40 Deionized water (μL) 40 40 0 0 PBS buffer solution (μL) 70 30 70 30 Tyrosinase solution (μL) 20 20 20 20 Total (μL) 130 130 130 130 The tyrosinase inhibition rate was calculated according to the formula as follows: Tyrosinase inhibition rate / % = [1-(D-C) / (B-A)]x100%.

[0049] The results are shown in Table 3.

[0050] Table 3 Inhibition rate of composition on tyrosinase Group Tyrosinase inhibition rate / % Composition 1 65.72 Composition 2 63.62 Composition 3 63.94 Composition ① 42.44 Composition ② 38.31 Composition ③ 47.62 Composition ④ 56.52 Composition ⑤ 54.91 Composition ⑥ 50.37 Composition ⑦ 10.64 Composition ⑧ 57.33 According to the results in Table 3, the composition in the present application has a significant effect of inhibiting tyrosinase. According to the results of composition 1 and composition ①-③, the Selaginella extract, mulberry root extract, and euglena extract in the present application have a significant synergistic effect. The use of nucleotide protein complex can significantly improve the inhibition of tyrosinase of the composition. According to the results of composition 1 and composition ④-⑤, the use of PDRN and SOD enzyme with Selaginella extract, mulberry root extract, and euglena extract can significantly improve the inhibition of tyrosinase of the composition, indicating that there is a significant synergistic effect between PDRN and SOD enzyme. According to the results of composition 1 and composition ⑥-⑦, there is a significant synergistic effect between Selaginella extract, mulberry root extract, and euglena extract and PDRN and SOD enzyme. According to the data of composition ⑦, the nucleotide protein complex composed of PDRN and SOD enzyme has poor inhibition effect on tyrosinase, but when used with Selaginella extract, mulberry root extract, and euglena extract, it can improve the inhibition effect of the composition composed of Selaginella extract, mulberry root extract, and euglena extract on tyrosinase, indicating that there is a significant synergistic effect between PDRN, SOD enzyme, Selaginella extract, mulberry root extract, and euglena extract. According to the results of composition 1-3 and composition ⑧, the mass fraction of Selaginella extract, mulberry root extract, euglena extract, PDRN, and SOD enzyme selected in the present application has the best effect within the range defined in the present application.

[0051] Human efficacy test: Test 2: Safety test Test A: Human skin patch test Test material: serum 1-5, serum ①-⑧, blank serum.

[0052] Subject selection: Healthy subjects aged 31-47 years old were selected, voluntarily participated and signed the informed consent, could complete the test as required during the test period, and the subjects were randomly grouped, with 30 subjects in each group corresponding to one test substance.

[0053] Experimental method: Qualified patch equipment was selected, 1 g of the test substance was placed in the patch tester and evenly coated, and then the patch tester was attached to the flexor of the forearm of the subject using an external low-sensitization adhesive tape. After 24 hours, the test substance was removed, and the skin reaction was observed and recorded at 0.5, 24 and 48 hours after removal, respectively.

[0054] Result evaluation: The skin adverse reaction grading was determined according to the skin adverse reaction grading of human use test in the “Cosmetic Safety Technical Specification” (2015 edition), and the grading standard was shown in Table 4, and the results were shown in Table 5.

[0055] Table 4 Skin adverse reaction grading standard Classification Phenomenon 0 level Skin has no reaction 1 level Skin appears pinkish red spots 2 level Skin appears red spots, infiltration and papules 3 level Skin appears red spots, edema, papules and blisters 4 level Skin appears red spots, edema and bullae Table 5 Results of human skin patch test

[0056] Test B: Human use test for sensitive skin Test substance: Serum 1-5, serum ①-⑧, and blank serum.

[0057] Subject selection: Healthy subjects aged 31-47 years old were selected, met the positive lactic acid stinging test, voluntarily participated and signed the informed consent, could complete the test as required during the test period, and the subjects were randomly grouped, with 30 subjects in each group corresponding to one test substance.

[0058] Experimental method: The subjects randomly divided the bilateral face into test side and control side, and after cleansing, the test substance was evenly applied to the facial skin of the test side according to the use method of the test substance, and the control side was not used. After 28 days of use, the subjects fed back the local skin reaction, and if there was an adverse reaction, the dermatologist evaluated the adverse reaction.

[0059] Result evaluation: The skin adverse reaction grading was determined according to the skin adverse reaction grading of human use test in the “Cosmetic Safety Technical Specification” (2015 edition), and the grading standard was shown in Table 4, and the results were shown in Table 6.

[0060] Table 6 Results of human use test

[0061] From the results of the human skin patch test, during the test period, serum 1-5 and serum ①-⑧ were safe, and the subjects had no adverse reactions.

[0062] From the results of the sensitive skin test, no adverse skin reactions occurred in the test period, indicating that serums 1-5 and serums 1-8 are safe, mild and non-irritating, and suitable for sensitive skin.

[0063] Test 3: Whitening efficacy detection Based on the results of the foregoing Table 3, the present application further detects the whitening efficacy of the serum containing the whitening composition containing PDRN and SOD enzyme, and the results are shown in Table 7.

[0064] Test sample: serums 1-5, serums 1-8, and blank serum.

[0065] Subjects: healthy subjects aged 31-47 years old were selected, with 30 subjects in each group corresponding to one test sample.

[0066] Test sample usage method: use the test sample once a day in the morning and evening, 0.5 mL each time; the application area is the face.

[0067] Test method: use the skin analyzer DermaLab Combo to detect the ITA value of the test area before skin application of the subjects, record it as the pre-use ITA value, and mark the measurement area. Then the subjects receive the test sample and use it according to the requirements, and the application area needs to completely cover the measurement area. The next day after the test is completed, return to the test point and detect the ITA value of the measurement area, record it as the ITA value after 56 days of application. Refer to the formula to calculate the ITA value change rate. The higher the ITA value change rate, the less the skin melanin, and the whiter the skin looks.

[0068] ITA value change rate / % = (ITA value after 56 days of use - pre-use ITA value) / pre-use ITA value x 100%.

[0069] Table 7 Effect of composition on skin whitening Test sample Number of subjects Pre-use ITA value ITA value after 56 days of use ITA value change rate / % Serum 1 30 24.64 33.38 35.47 Serum 2 30 25.12 29.36 16.88 Serum 3 30 24.84 34.27 37.96 Serum 4 30 24.49 32.71 33.56 Serum 5 30 25.94 34.29 32.19 Serum ① 30 25.53 31.25 22.41 Serum ② 30 25.01 29.93 19.67 Serum ③ 30 24.85 31.27 25.84 Serum ④ 30 24.63 31.86 29.35 Serum ⑤ 30 24.23 30.91 27.57 Serum ⑥ 30 25.26 32.21 27.51 Serum ⑦ 30 25.69 28.06 9.23 Serum ⑧ 30 24.11 31.42 30.32 Blank serum 30 24.50 25.14 2.61 According to the results in Table 7, serums 1-5 and serums 1-8 have certain whitening effect; comparing the results of serums 1-3 and blank serum, it can be seen that the whitening composition containing PDRN and SOD enzyme has certain whitening effect; comparing the results of serum 1 and serums 4-5 and serum 8, it can be seen that the mass fraction of each component in the whitening composition containing PDRN and SOD enzyme is within the range defined in the present application, and the whitening effect is better; comparing the results of serum 1 and serums 1-6, it can be seen that there is a significant synergistic effect between the components in the whitening composition containing PDRN and SOD enzyme in the present application.

[0070] The embodiments described above are only part of the embodiments of the present application, rather than all the embodiments. The detailed description of the embodiments of the present application is not intended to limit the scope of the claimed present application, but only represents selected embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

Claims

1. A whitening composition containing PDRN and SOD enzyme, characterized in that, The composition comprises the following components in parts by weight: Selaginella extract: 2-4 parts; Mulberry root extract: 1-3 parts; Oenanthera extract: 8-10 parts; Nucleotide-protein complex: 0.5-1.5 parts; The nucleotide-protein complex includes PDRN and SOD enzyme.

2. The composition according to claim 1, characterized in that, The average molecular weight of the PDRN is 50-850 kDa; the SOD enzyme activity is 50,000-200,000 U / g.

3. The composition according to claim 1, characterized in that, The mass ratio of PDRN to SOD enzyme in the nucleotide protein complex is 1:0.6-1.

3.

4. The use of the whitening composition containing PDRN and SOD enzyme as described in any one of claims 1-3 in the preparation of cosmetics with whitening effects.

5. The application as described in claim 4, characterized in that, The dosage form of the whitening cosmetic includes any one of face cream, lotion, and serum.

6. A whitening serum, characterized in that, The serum comprises 0.1-5 wt% of the whitening composition containing PDRN and SOD enzyme as described in any one of claims 1-3.

7. The essence as described in claim 6, characterized in that, The serum also includes moisturizers, preservatives, thickeners, pH adjusters, and deionized water.

8. The essence as described in claim 7, characterized in that, The moisturizer is at least one of sodium hyaluronate, glycerin, and squalane.

9. The essence as described in claim 7, characterized in that, The preservative is at least one of p-hydroxyacetophenone, ethylhexylglycerin, and octyl glycol.

10. The essence as described in claim 7, characterized in that, The thickener is at least one of xanthan gum, hydroxyethyl cellulose, ammonium acryloyl dimethyl taurate / VP copolymer, and sodium polyacryloyl dimethyl taurate; the pH adjuster is tromethamine.

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