Galactose oral compositions and uses thereof

Abstract

A galactose oral composition containing galactose, an antioxidant, and a buffering agent. The galactose oral composition contains 1% to 80% by weight of galactose. The antioxidant is selected from vitamin A, vitamin C, vitamin E, ethylenediaminetetraacetic acid (EDTA), sodium bisulfite, flavonoids, polyphenols, diethylenetriaminepentaacetic acid (DTPA), and NTA-nitrilotriacetic acid (NTA). The buffering agent is selected from ascorbic acid buffer, citrate buffer, phosphate buffer, acetate buffer, carbonate buffer, and triethanolamine buffer. The galactose oral composition of the present invention can be used to detect an individual's galactose metabolic ability and evaluate liver function.

Description

[Technical Field]

[0001] The present invention relates to an oral galactose preparation used for detecting galactose levels in blood. [Background technology]

[0002] Galactose is an epimer of glucose and one of the main components of lactose. Galactose is primarily metabolized in the liver and converted to glucose, then converted to glycogen and stored in the liver. Although galactose metabolism is significantly affected by liver disease, the maximum galactose elimination capacity (GEC) concentration in blood and the galactose concentration determined by the galactose single point method (GSP) can be used as clinical indicators of liver function.

[0003] For many years, GEC has been used as a method for quantitatively assessing human liver function. However, the GEC test requires a large number of blood samples to establish a calibration curve, making clinical application difficult. Many studies have used GSP to assess human liver function. Liver function includes hepatic blood flow status, liver enzyme status, and metabolic capacity of galactose.

[0004] Tang HS and Hu OYP (Digestion 1992;52:222-231) et al. demonstrated that the GSP method can accurately identify various liver diseases, including chronic hepatitis, cirrhosis, and liver cancer. It can also be used to assess residual liver function. The GSP method has been recommended as a benchmark by the U.S. Food and Drug Administration (FDA), and has been validated as a highly convenient and feasible method for assessing residual liver function in patients with common liver diseases. Furthermore, the GSP method is one of the recommended liver function tests in the FDA's industry guidelines.

[0005] Previously, subjects' blood galactose concentrations were measured as GSP values ​​(μg / ml) 60 minutes after fasting subjects received a rapid intravenous injection of 0.5 g / kg of galactose over a three-minute period. However, intravenous injection is invasive, causes psychological stress for the subjects, and can lead to tissue damage, pain, and potential complications. It is particularly unpopular with elementary school and kindergarten children, and requires considerable effort to successfully inject into the small blood vessels.

[0006] Therefore, how to design a non-invasive galactose formulation that can be orally administered to a subject and can be accurately detected by the GSP method has been an important topic to be solved by the present invention. Summary of the Invention

[0007] An object of the present invention is to provide a galactose oral composition comprising galactose, a buffer and an antioxidant, wherein the galactose oral composition has a pH value ranging from 2.0 to 10.0, and the galactose comprises D-(+)-galactose, L-(-)-galactose, stable isotope galactose, a galactose ring, or a galactose derivative.

[0008] In order to achieve the above-mentioned object of the present invention, the aforementioned antioxidant is selected from the group consisting of vitamin A, vitamin C, vitamin E, sodium bisulfite, polyphenols, ethylenediaminetetraacetic acid (EDTA), flavonoids, diethylenetriaminepentaacetic acid (DTPA), and NTA-nitrilotriacetic acid (NTA).

[0009] To achieve the above-mentioned object of the present invention, the buffer is selected from the group including at least one of ascorbic acid buffer, citrate buffer, phosphate buffer, acetate buffer, carbonate buffer, and triethanolamine buffer.

[0010] To achieve the above-mentioned object of the present invention, the aforementioned galactose oral composition exhibits a pH value ranging from 3.0 to 6.0.

[0011] To achieve the above-mentioned object of the present invention, the aforementioned galactose oral composition is a food composition and / or a pharmaceutical composition.

[0012] To achieve the above-mentioned object of the present invention, the aforementioned galactose oral composition further comprises at least one of an emulsifier, a colorant, a flavoring agent, a sweetener, a preservative, an excipient, a bulking agent, a stabilizer, and a dispersing agent.

[0013] To achieve the above-mentioned object of the present invention, the sweetener is selected from the group consisting of at least one of D-sorbitol, D-sorbitol 70% solution, D-xylitol, glycyrrhizin, trisodium glycyrrhizinate, D-mannitol, saccharin, saccharin sodium, sodium cyclamate, calcium cyclamate, aspartame, steviol glycoside, licorice extract, acesulfame potassium, ammoniated glycyrrhizin, monoammonium glycyrrhizinate, maltitol, maltitol syrup (hydrogenated glucose syrup), isomalt (hydrogenated palatinose), lactitol, monoglucuronyl glycyrrhetinic acid, thaumatin, erythritol, sucralose, and neotame.

[0014] In order to achieve the above object of the present invention, the spice is selected from the group comprising at least one of cherry, lemon, lime, mandarin, orange, tangerine, mint, strawberry, banana, caramel, licorice, passion fruit, peach, raspberry, tutti frutti, grapefruit, vanilla, cream, chocolate and grape.

[0015] Another object of the present invention is to provide a type of the above-mentioned oral galactose composition, which is a preparation agent for examining the hepatic blood flow status, liver enzyme status, and metabolic capacity of galactose.

[0016] To achieve the above-mentioned objectives of the present invention, each oral dose of the galactose oral composition ranges from 0.0 lg / kg to 5 g / kg.

[0017] Another object of the present invention is to provide a galactose composition comprising galactose, a buffer, and an antioxidant, wherein the galactose composition exhibits a pH value in the range of 2.0 to 10.0, the galactose composition maintains its original color under high temperature conditions, and the galactose comprises at least one of D-(+)-galactose, L-(-)-galactose, stable isotope galactose, a galactose ring, or a galactose derivative.

[0018] In order to achieve the above object of the present invention, the aforementioned high temperature means a temperature of 80°C to 250°C.

[0019] In achieving the above-mentioned objectives of the present invention, the aforementioned galactose composition is a nutritive sweetener for diabetics.

[0020] In achieving the above-mentioned objectives of the present invention, the galactose compositions described above can be added to foods, nutrients, and formulas.

[0021] Another object of the present invention is to provide one of the above-mentioned galactose compositions as a preparation agent for examining the hepatic blood flow status, liver enzyme status, and metabolic capacity of galactose.

[0022] To achieve the above-mentioned objectives of the present invention, each dose of the galactose composition ranges from 0.01 g / kg to 5 g / kg. [Brief explanation of the drawings]

[0023] [Figure 1] Figure 1 shows the results of the test report for the galactose oral solution product. [Figure 2] Figure 2 shows the relative distribution of GSP results from intravenous injection of galactose and OGSP results from oral administration of galactose. [Figure 3] FIG. 3 shows the distribution of OGSP results following oral galactose administration in subjects with normal, moderately, and severely impaired liver function. [Figure 4] FIG. 4 shows the correlation between OGSP results and liver cirrhosis following oral administration of galactose. [Figure 5] FIG. 5 shows the correlation between GSP results and liver cirrhosis with intravenous galactose injection. [Figure 6] FIG. 6 shows the correlation between OGSP results and the degree of end-stage liver disease following oral administration of galactose. [Figure 7] FIG. 7 shows the correlation between GSP results with intravenous galactose injection and the degree of end-stage liver disease. [Figure 8] FIG. 8 shows the changes in OGSP at various time points after oral administration of galactose to animals with nonalcoholic steatohepatitis (NASH). DETAILED DESCRIPTION OF THE INVENTION

[0024] The present invention will be exemplified below, but the present invention is not limited to the following embodiments.

[0025] In the present invention, in order to provide a good galactose oral formulation, various kinds and concentrations of buffers and antioxidants are added to prepare galactose oral solutions with different pH values, and stability tests are carried out.

[0026] The galactose of the present invention refers to galactose containing at least one of D-(+)-galactose, L-(-)-galactose, and stable isotope galactose.

[0027] Antioxidants in this invention refer to antioxidants including at least one of vitamin C and / or sodium bisulfite, vitamin A, vitamin E, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), flavonoids, polyphenols, and NTA-nitrilotriacetic acid (NTA).

[0028] The buffer of the present invention refers to a buffer containing at least one of a citrate buffer, a phosphate buffer, an acetate buffer, a carbonate buffer, an ascorbic acid buffer, and a triethanolamine buffer.

[0029] Preparation of galactose oral solution: 50 liters of 45°C water is poured into a barrel dispenser, followed by the addition of 155 g of sodium citrate and stirring until completely dissolved. After adjusting the pH to 4.5±0.5, 500 g of sodium bisulfite is added and stirred until completely dissolved, 40 kg of D-galactose is added and stirred until completely dissolved, and then 36 g of sodium citrate is added and stirred until completely dissolved. After adjusting the pH to 4.5±0.5, the mixture is filled with 45°C water until the total volume reaches 100 liters, then stirred for 10 minutes and filtered through a 0.22 μm pore size filter. After uniform mixing, the mixture is poured into several 100 ml glass bottles, sampled, and immediately sealed. Finally, each bottle is heated at 121°C (1.2 kg / cm). 2 The bottles were placed in a high-pressure steam pot (2000 psi). After sterilization for 15 minutes, the bottles were removed and sampled. Table 1 shows the results of the long-term stability test of the galactose oral solution. The formulations were shown to have good stability even after 37 to 148 months.

[0030] [Table 1]

[0031] The galactose content is 1% to 80%. In this method, galactose is prepared as a 1% to 80% solution at high temperature, and then diluted to a more suitable content of 4% to 40% by weight. The buffer should not be added in an amount greater than 0.001% to 5% by weight. The antioxidant should not be added in an amount greater than 0.001% to 5% by weight. Suitable oral solution formulations can be prepared by appropriately selecting buffers and antioxidants to achieve the following component contents: 0.001M to 1M sodium bisulfite and / or vitamin C, vitamin A, vitamin E, flavonoids, ethylenediaminetetraacetic acid (EDTA), polyphenols, diethylenetriaminepentaacetic acid (DTPA), and / or NTA-nitrilotriacetic acid (NTA) as antioxidants; and / or a buffer solution adjusted to a pH value ranging from 4.0 to 9.0 with one of the following seven buffer solutions: 0.001M to 1M citrate buffer solution, phosphate buffer solution, acetate buffer solution, carbonate buffer solution, ascorbic acid buffer solution, and triethanolamine buffer solution. A stable oral solution formulation can be obtained by adding 0.01% citrate buffer and 0.5% sodium bisulfite to achieve a pH value of 4.5.

[0032] The oral solution prepared using the above formulation has a galactose concentration of 400 mg / ml and a volume of 100 ml. The resulting galactose oral solution was then tested, and the results are shown in Figure 1. From the results in Figure 1, the color, component content, pH, and volume of the galactose oral solution of the present invention are standard values. USP-XXII regulations regarding 5-hydroxymethylfurfural, the main decomposition product in dextrose oral liquids, and other related regulations regarding the content of related substances, stipulate that the absorbance value of water as a blank control solution must not exceed 0.25 when measured at a wavelength of 284 nm with a dextrose concentration of 1 / 250 g / ml. The content of 5-hydroxymethylfurfural in the galactose oral solution of the present invention is only 0.02, even after long-term storage. Therefore, according to the results in Figure 1 and Table 1, the galactose oral solution of the present invention can be stored for a long period of time and maintain stability.

[0033] Example 1: Effect of antioxidants and buffers on galactose stability. Oral solution The galactose oral solution was prepared with a 4% galactose concentration and a volume of 100 ml. As shown in Table 2, the stability test results showed that all formulations containing vitamin C (0.5 M) as an antioxidant changed color after 168 hours at 80°C. However, when sodium bisulfite (0.1 M, 0.5 M) was added as an antioxidant and the pH was adjusted to 4.5, the formulations did not change color even after 168 hours at 80°C.

[0034] [Table 2]

[0035] The galactose oral solution was prepared with a 4% galactose concentration and a volume of 100 ml. For stability testing, five different buffer solutions with a 0.01 M buffer concentration were prepared by adding antioxidants. The buffers were selected from a group including citrate buffer, phosphate buffer, acetate buffer, carbonate buffer, and triethanolamine buffer. The antioxidants were sodium bisulfite and vitamin C at 0.01 M concentrations. According to the results in Table 3, all formulations containing vitamin C as an antioxidant showed color changes and decreased stability after 168 hours. However, all formulations containing sodium bisulfite as an antioxidant showed no color changes at pH 7.35 or 4.5, regardless of buffer. Observation of galactose formulations 1-30 containing citrate buffer and sodium bisulfite antioxidant at pH 4.5 revealed superior stability in terms of pH and color change.

[0036] [Table 3]

[0037] The galactose oral solution was prepared with a 4% galactose concentration and a volume of 100 ml. For stability testing, five different 1M buffer solutions were prepared with antioxidants. The buffers were selected from a group including citrate buffer, phosphate buffer, carbonate buffer, and triethanolamine buffer, and the antioxidant was either 0.5M sodium bisulfite or vitamin C. According to the results in Table 4, all formulations containing 0.5M vitamin C as an antioxidant showed color changes after 168 hours, indicating poor stability. Some formulations containing 0.5M sodium bisulfite as an antioxidant also showed color changes after 168 hours at 80°C. Furthermore, color changes occurred after one week of storage in 1M carbonate buffer at pH 7.35 and 1M triethanolamine buffer at pH 4.5. This indicates that increasing the sodium bisulfite and buffer concentrations together decreases the stability of the formulation. The remaining four high-concentration buffer systems, i.e., citrate buffer, phosphate buffer, carbonate buffer, and triethanolamine buffer, are stabilized by adding high concentrations of sodium bisulfite antioxidants at a pH of 4.5, but the citrate and acetate buffer environments produce better results. No precipitates were observed after storing formulations 31-50 at 80°C for one week.

[0038] [Table 4]

[0039] Embodiment 2: Effect of pH value on stability of galactose oral solution. Stability testing of galactose oral solutions was performed at pH values ​​ranging from 5.02 to 8.52, with a galactose concentration of 4%, a volume of 100 ml, and no buffering or antioxidants. According to USP XXII regulations regarding 5-hydroxymethylfurfural, the main degradation product in dextrose oral solutions, and other related regulations regarding the content of related substances, the absorbance value of the blank control solution containing water must not exceed 0.25 when measured at a wavelength of 284 nm at a dextrose concentration of 1 / 250 g / ml. Therefore, the absorbance value of the 4% galactose oral solution of the present invention must not exceed 2.5. Results showed that a pH of 4.5 resulted in minimal variation between the formulations before and after sterilization. This indicates that stability is better in a low pH environment.

[0040] Example 3: Effect of antioxidant concentration on stability of galactose oral solution. The stability of galactose oral solutions prepared with different antioxidant concentrations was observed, and it was found that as the antioxidant concentration increased, both the pH and absorbance values ​​showed minimal changes before and after sterilization, and that the addition of an antioxidant was better than the addition of no antioxidant. Using 0.01M citrate buffer, both the pH value of the oral solution and the sodium bisulfite antioxidant concentration were adjusted. As a result, under acidic conditions, when the sodium bisulfite antioxidant concentration was 1%, both the pH value and absorbance values ​​showed minimal changes before and after sterilization.

[0041] Both the pH value and the sodium bisulfite antioxidant concentration of the oral solution were adjusted using 0.01M phosphate buffer solution. Results showed that under acidic conditions and with a 1% sodium bisulfite antioxidant concentration, both the pH and absorbance values ​​showed minimal changes before and after sterilization, indicating excellent stability. When both the pH value and the sodium bisulfite antioxidant concentration of the oral solution were adjusted using 0.01M acetate buffer solution, both the pH value and the sodium bisulfite antioxidant concentration showed minimal changes before and after sterilization, indicating excellent stability, at a 1% sodium bisulfite antioxidant concentration. When both the pH value and the sodium bisulfite antioxidant concentration of the oral solution were adjusted using 0.01M triethanolamine buffer solution, both the pH value and the sodium bisulfite antioxidant concentration showed minimal changes before and after sterilization, indicating excellent stability, at a 1% sodium bisulfite antioxidant concentration.

[0042] Based on the minimal change in pH and color, a citrate buffer-containing formulation can be selected as an ideal model system. Further investigations could involve increasing the galactose concentration to 40%. In systems using pure water, the solution becomes more yellow with increasing galactose concentration. In acidic citrate buffer systems, the addition of different concentrations of sodium bisulfite has little effect on the pH before and after sterilization. However, when the sodium bisulfite concentration exceeds 0.5%, the color of the oral solution remains unchanged and the change in absorbance is minimal. In alkaline citrate buffer systems, the color of the oral solution changes significantly after one week of storage at 80°C, regardless of the concentration of sodium bisulfite added.

[0043] Common sugars such as sucrose and galactose discolor at temperatures as high as approximately 80°C, and galactose discolors at high temperatures both in solid and solution. The galactose oral solution formulation of the present invention does not change color even when stored at 80°C or sterilized at 121°C. This means that the galactose oral solution formulation of the present invention can be used as a sweetening supplement at temperatures as high as baking. Galactose is sweet and caloric, but does not affect blood sugar levels, making it a suitable nutritional sweetener for diabetics or those who need to control their blood sugar levels.

[0044] The practical application of the galactose oral composition to the detection of galactose concentration in blood will be further demonstrated below.

[0045] Subject conditions Subject selection criteria: 1. Men or women aged 20-85. 2. Agree to sign the subject consent form and willing to cooperate with all experimental procedures. Subject Exclusion Criteria: 1. Patients with galactosemia who have an allergic reaction to galactose. 2. People who have undergone total or subtotal gastrectomy, celiac disease and bowel resection, and have other medical history. 3. Diabetes. 4. Children or people with disabilities. 5. Any other medically related reason acceptable to the Principal Investigator will exclude you from this trial.

[0046] Clinical trial methods, procedures, and related clinical trials (1) Preliminary screening Before the screening period, subjects must sign a subject consent form. Before grouping subjects with the investigational drug, subjects must cooperate with the investigator by recording their past medical history (including medication history) in order to participate in the clinical trial. (2) Commencement of clinical trials Each subject will undergo two additional liver function tests, GSP and OGSP, over a period of time. The time interval between these two tests must be at least 12 hours. Subjects will also be required to fast for 6 hours before the test day.

[0047] OGSP test: Subjects were instructed to drink 1.25 ml of galactose solution per kg of body weight (400 mg of galactose per ml), i.e., 0.5 g / kg of galactose per kg of body weight. After 3-5 minutes of oral administration, subjects were given at least 20 ml of water. Sixty minutes after the oral administration, blood was drawn from the finger and 0.5 ml of whole blood was slowly dripped onto a galactose test strip to complete the test.

[0048] Galactose is present in an amount of 1% to 80% by weight, preferably 4% to 40%, buffering agent is present in an amount of 0.001% to 5%, with or without addition, and antioxidant is present in an amount of 0.001% to 5%, with or without addition. The antioxidant is selected from the group including at least one of vitamin C and / or sodium bisulfite, vitamin A, vitamin E, polyphenols, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), flavonoids, and / or NTA-nitrilotriacetic acid (NTA). The buffer is selected from the group including at least one of citrate buffer, phosphate buffer, acetate buffer, carbonate buffer, ascorbic acid buffer, and triethanolamine buffer.

[0049] GSP: Subjects receive a 1.25 ml galactose injection per kg of body weight (400 mg galactose per ml), or 0.5 g / kg of galactose per kg of body weight. The galactose injection is completed within 3-5 minutes. 60 minutes after the injection, a fingernail blood sample is taken, and 0.5 ml of whole blood is slowly dripped onto a galactose test strip to complete the test.

[0050] Example 4: OGSP results with oral administration of galactose and GSP results with intravenous injection of galactose. Figures 2 and 3 are relative distribution diagrams of GSP results from intravenous injection of galactose and OGSP results from oral administration of galactose for 127 subjects (56 with normal liver function and 71 with liver dysfunction). According to the recommendations by Digestion 1992;52:222-231, the subjects could be divided into three groups based on the GSP values (GSP) of intravenously administered galactose. Here, when GSP < 280 μg / ml, the subjects are defined as showing normal liver function. When 280 < GSP < 480 μg / ml, the subjects are defined as having moderate liver dysfunction, and when GSP > 480 μg / ml, the subjects are defined as having severe liver dysfunction. According to the results of Figures 2 and 3, the OGSP values from oral galactose are higher than those from intravenous galactose, the OGSP values from oral galactose increase with the severity of liver dysfunction, and a positive correlation is observed between OGSP and GSP. In the group of subjects showing normal liver function, the OGSP from oral administration of galactose is 318 ± 27 μg / ml (mean ± standard error SE). Here, the minimum value is 18 μg / ml and the maximum value is 887 μg / ml. In subjects with mild or moderate liver dysfunction, the OGSP from oral administration of galactose is 590 ± 40 μg / ml (mean ± standard error SE), the minimum value is 294 μg / ml, and the maximum value is 1282 μg / ml. In subjects with severe liver dysfunction, the OGSP from oral administration of galactose is 777 ± 48 μg / ml (mean ± standard error SE), the minimum value is 293 μg / ml, and the maximum value is 1499 μg / ml. Figure 5 shows the OGSP from oral administration of galactose and the GSP results from intravenous injection of galactose for three groups of subjects. As can be seen from the results, the OGSP values from oral administration of galactose increase with the severity of liver dysfunction. In particular, the OGSP values from oral galactose are higher than those from intravenous galactose. From Figures 2 and 3 and Table 5, it can be judged that the main range (mean ± 2 times the standard error SE) of OGSP from oral administration of galactose in the group of subjects with normal liver function is about 264 - 372 μg / ml.In the target group with mild or moderate liver dysfunction, the main range of OGSP (mean ± 2 times the standard error SE) by oral administration of galactose is about 510 - 670 μg / ml, and in the target group with severe liver dysfunction, the main range of OGSP (mean ± 2 times the standard error SE) by oral administration of galactose is about 681 - 873 μg / ml. Even when the results vary depending on the subject, in the target group with normal liver function, the OGSP by oral administration of galactose does not exceed 670 μg / ml, but the OGSP of subjects with liver dysfunction may exceed 370 μg / ml. Therefore, subjects with OGSP exceeding 370 μg / ml need to undergo additional liver function tests.

[0051]

Table 5

[0052] Embodiment 5: Relationship between blood biochemical values, OGSP results by oral administration of galactose, and GSP results by intravenous injection of galactose 127 subjects (excluding diabetic patients) were divided into three groups according to the GSP value (GSP) of intravenously administered galactose. Here, when GSP < 280 μg / ml, the subject is defined as having normal liver function, when 280 < GSP < 4800 μg / ml, the subject is defined as having moderate liver dysfunction, and when GSP > 480 μg / ml, the subject is defined as having severe liver dysfunction. Figure ⑥ shows the relationship between blood biochemical values, OGSP results by oral administration of galactose, and GSP results by intravenous injection of galactose in the three target groups. From this result, it is shown that both the GSP value by intravenous galactose and the OGSP value of oral galactose are significantly correlated with numerous blood biochemical indicators. Here, AST (aspartate aminotransferase) and ALT (alanine aminotransferase) are indicators of liver dysfunction, and the correlation between the OGSP value by oral galactose and AST, ALT is greater than the correlation between the GSP value by intravenous galactose and AST, ALT.

[0053] <H [Table 6]

[0054] Embodiment 6: Correlation of oral galactose-induced OGSP values, intravenous galactose-induced GSP values, and severe liver disease The GSP test will be performed on 42 patients with liver cirrhosis after oral administration of galactose. Figure 3 shows the correlation between oral galactose OGSP results and liver cirrhosis. The Child-Pugh index (Child-Pugh score) is typically used as a clinical index to estimate the severity of liver cirrhosis. Figure 4 shows that oral galactose OGSP values ​​are positively correlated with the Child-Pugh score (r = 0.817, p < 0.005). Compared with the conventional intravenous galactose GSP results (Figure 5), oral galactose OGSP values ​​are higher. However, both oral galactose OGSP values ​​and intravenous galactose GSP values ​​are positively correlated with liver cirrhosis. Therefore, it is possible to estimate liver cirrhosis using both oral galactose OGSP values ​​and intravenous galactose GSP values.

[0055] The Model for End-Stage Liver Disease (MELD) is an effective predictor of short- and medium-term mortality in patients with end-stage liver disease. This evaluation index is simple, objective, and easily calculated. Therefore, it is widely used in the diagnosis and treatment of liver disease. OGSP tests were performed on 42 patients with liver cirrhosis after oral administration of galactose. Figure 5 shows the correlation between oral galactose OGSP results and MELD. Figure 6 shows that oral galactose OGSP values ​​are positively correlated with MELD (r = 0.660, p < 0.005). Compared with the conventional intravenous galactose GSP results (Figure 7), oral galactose OGSP values ​​are higher. However, both oral galactose OGSP values ​​and intravenous galactose GSP values ​​are positively correlated with MELD. Therefore, MELD can be estimated using both oral galactose OGSP values ​​and intravenous galactose GSP values.

[0056] Embodiment 7: Oral galactose-induced OGSP changes in mice with NASH (non-alcoholic steatohepatitis) Figure 8 shows the OGSP results (OGSP) at various time points after oral galactose administration. Mice develop nonalcoholic hepatitis (NASH) when fed a high-fat diet. All animals with NASH exhibit higher OGSP values ​​than normal individuals within 10 to 90 minutes after oral administration, but OGSP values ​​change significantly within 30 to 90 minutes after oral administration. The results indicate that NASH can be predicted from the OGSP value induced by oral galactose, and that the value 30 to 80 minutes after oral galactose administration is ideal for this prediction.

[0057] The above detailed description is intended to specifically illustrate possible embodiments of the present invention, but these embodiments in no way limit the patent scope of the present invention, and all embodiments or improvements thereof implemented without departing from the scope of the present invention are encompassed within the patent scope of the present invention.

[0058] The present invention has the following advantages over the prior art: (1) The galactose oral composition of the present invention is a non-invasive galactose preparation that can be orally administered to a subject for the GSP method; (2) The galactose oral composition formulation maintains good quality and has good stability and performance after long-term storage and high-temperature sterilization; and (3) The oral galactose composition of the present invention can detect galactose metabolism levels that exceed those detected by the intravenous galactose method.

Claims

1. 1. A galactose oral composition comprising: Galactose; a buffering agent; and an antioxidant in an amount of 0.001 to 99 volume percent; the galactose oral composition has a pH value in the range of 3.0 to 6.0; the galactose includes at least one of D-(+)-galactose, L-(-)-galactose, or stable isotope galactose; the antioxidant does not include vitamin C; and The antioxidant includes sodium bisulfite. Galactose oral composition.

2. the buffer is selected from the group consisting of a citrate buffer, a phosphate buffer, an acetate buffer, a carbonate buffer, and a triethanolamine buffer; The galactose oral composition of claim 1.

3. The galactose oral composition is a food composition or a pharmaceutical composition; The galactose oral composition of claim 1.

4. the galactose oral composition further comprises at least one of an emulsifier, a colorant, a spice, a flavoring, a sweetener, a preservative, an excipient, a bulking agent, a stabilizer, a dispersing agent, an acceptable food additive, or an acceptable pharmaceutical excipient; The galactose oral composition of claim 1.

5. The galactose oral composition further comprises a sweetener; the sweetener is selected from the group consisting of D-sorbitol, D-sorbitol 70% solution, D-xylitol, glycyrrhizin, trisodium glycyrrhizinate, D-mannitol, saccharin, sodium saccharin, sodium cyclamate, calcium cyclamate, aspartame, steviol glycoside, licorice extract, acesulfame potassium, ammoniated glycyrrhizin, monoammonium glycyrrhizinate, maltitol, maltitol syrup (hydrogenated glucose syrup), isomalt (hydrogenated palatinose), lactitol, monoglucuronyl glycyrrhetinic acid, thaumatin, erythritol, sucralose, and neotame; The galactose oral composition of claim 1.

6. The galactose oral composition further comprises a spice; the spices are selected from the group consisting of cherry, lemon, lime, mandarin, orange, tangerine, mint, strawberry, banana, caramel, licorice, passion fruit, peach, raspberry, tutti frutti, grapefruit, vanilla, cream, chocolate and grape, The galactose oral composition of claim 1.

7. 1. A galactose oral composition comprising: Galactose; a buffering agent; and an antioxidant in an amount of 0.001 to 99 volume percent; the galactose oral composition has a pH value in the range of 3.0 to 6.0; The galactose oral composition maintains its original color under elevated temperature conditions, the elevated temperature being a temperature of 80°C to 250°C; and the galactose includes at least one of D-(+)-galactose, L-(-)-galactose, or stable isotope galactose; the antioxidant does not include vitamin C; and The antioxidant includes sodium bisulfite. Galactose oral composition.

8. The galactose oral composition is a nutritive sweetener. The galactose oral composition of claim 7.

9. The galactose oral composition can be added to foods, nutrients, and formulas. The galactose oral composition of claim 7.

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