Abstract:
The present invention provides a test meal kits that are used in the diagnosis of gastrointestinal disorders characterized by changes in the rate of gastric emptying; and, with a breath test or a nuclear scintigraphy scan, are used to measure a half-gastric emptying time useful for therapy monitoring of gastrointestinal disorders in clinical.

Description:
FIELD OF THE INVENTION  
       [0001]     The present invention relates to a measurement; more particularly, relates to a test meal kits that are used in the diagnosis of gastrointestinal disorders characterized by changes in the rate of gastric emptying, which kit contains an isotope tracer and a dry mix provided separately to minimize concerns on the stability and the FDA regulations; and, with a breath test or nuclear scintigraphy scan, to measure a half-gastric emptying time useful for therapy monitoring of gastrointestinal disorder in clinical.  
       BACKGROUND OF THE INVENTION  
       [0002]     A current method for measuring gastric emptying, called a nuclear scintigraphy scan, uses a radioactive material of a Tc-99 m (metastable Technetium-99) sulfur colloid which is injected to an egg to be further prepared as an omelet; and, requires the patient to lie still for more than three hours for a scanning. There are many disadvantages. First, the between-day coefficient variance of the measurement for an individual is more than 20% since the Tc-99 m sulfur colloid in the omelet does not distribute homogeneously. Second, although stuffs are fresh-made and fresh-used, the preparation process is inconvenient and difficult to control quantity. Furthermore, it needs expensive nuclear imaging suites, usually available only in major centers, and its cost effect is low. So, the expense and the inconvenience of the scintigraphy test lead to the creation of a simplified breath test.  
         [0003]     The breath test for the measurement of a gastric emptying of solids, labeled with a carbon-13 ( 13 C) octanoic acid or a carbon-14 ( 14 C) octanoic acid, is referred to Ghoos et al (1993), “Measurement of Gastric Emptying Rate of Solids by Means of a Carbon-Labeled Octanoic Acid Breath Test”, Gastroenterology 104, 1640-1647 and Maes et al (1994), “Combined Carbon-13-Glycine/Carbon-14-Octanoic Acid Breath Test to Monitor Gastric Emptying Rates of Liquids and Solids”, J Nucl Med 35, 824-831. In brief, after an overnight fast, the subject is given a test meal comprising a scrambled egg with the yolk doped with a  13 C octanoic acid or a  14 C octanoic acid. The yolk and the egg white are baked separately but are injected together with two slices of white bread and margarin, followed immediately by water. The test is based on a prompt solubilization of the  13 C octanoic acid or the  14 C octanoic acid in an egg yolk and the disintegration of the labeled solid phase in the duodenum, followed by a rapid absorption by the intestinal cells and a preferential oxidation to  13 CO 2  in the liver. The appearance of  13 CO 2  in a breath is primarily determined by the rate of delivery of the test meal from the stomach into the duodenum. Breath samples are collected and analyzed to get a half-emptying time and a lag phase, which are parameters for the calculation of a gastric emptying rate. All stuffs are fresh-made and fresh-used. The preparation is time consuming and it is hard to control the quality and the quantity. Besides, the coefficient variance of the measurement is more than 20% and the shelf-life is short. There can be difficulty on a uniform incorporation of the isotope tracers into the egg, since only the yolk mixed with  13 C-octanoic acid or  14 C-octanoic acid yet not the whole egg. In addition, meal homogeneity is difficult to maintain. Eggs, for example, vary in caloric content, size and composition, so that non-standardized cooking conditions can affect the outcome of the test and prevent intra-clinic comparison of the test results. Furthermore, the palatability was less than desirable because of the unpleasant taste, the pungent aroma of the octanoic acid, and the high viscosity at a room temperature.  
         [0004]     For solving these problems, Peter (DK U.S. Pat. No. 5,707,602, 1998), Spathe (Isot. Environ. Health Stud., 1998) and Meiler (WO02/062399A1) provide a biscuit with a sealed storage which is prepared with either  13 C-Spidina platenesis to wheat, or  13 C sodium acetate to wheat or sugar syrup. Pre-made products certainly have a shorter shelf-life than a dry mix. In addition, the incorporation of  13 C isotope tracer directed into the biscuit presents FDA regulatory hurdles that must be addressed, which can be avoided by not mixing the  13 C isotope tracer into a food product. Additionally, the growth of algae under specialized conditions costs additional expenses to the final test. The algae also may cause an adverse allergic reaction to a patient and may be less than palatable. The  13 C sodium acetate is not evenly incorporated into the food so that the CV (coefficient variance) of a gastric emptying measurement with a  13 C sodium acetate breath test is still more than 10%. Furthermore, the chemical stability of  13 C sodium acetate is poor so that the accuracy of the results is hard to maintain. Ghoos (2001, WO01/72342A1) prepares a test cake through a microwave by instantly mixing a dry egg yolk mix and  13 C octanoic acid. Wagner (2003, U.S. Pat. No. 6,548,043 B1) stores a  13 C octanoic acid and a standardized dry mix separately. The dry mix for the test meal is standardized in several respects, including the caloric content, the volume, the carbohydrate, the fat and the protein proportions; and is packed in a stable dry mix form, which can be easily shipped and stored indefinitely at room temperature. The test meal is constituted on site with liquid and  13 C octanoic acid; then, is cooked and is administered to a patient, followed by an appropriate diagnostic measurement, such as a  13 CO 2  breath test. One of the disadvantages is that the delivery system is only allowed to measure the solid emptying due to the insolubility of the  13 C octanoic acid. Other disadvantages include the high cost of the octanoic acid, the low speed of adsorption and metabolism in body, and the longer testing time required. Although the test meal is made by an instant solubilization and an instant preparation and is very close to a true meal either in the caloric content or in the nutrition proportions, inconvenience still exists that it is not palatable and toxic due to the characteristics of the octanoic acid and so it limits its clinical usage. In addition, the CV of the gastric emptying measurement by a  13 C octanoic acid breath test is more than 20%. The precision is poor and it could not be applied to a liquid or a semi-solid gastric emptying system due to the water insolubility of the octanoic acid. So, the prior arts do not fulfill users&#39; requests on actual use.  
       SUMMARY OF THE INVENTION  
       [0005]     The present invention is a standard, easy to use, and rapidly absorbed test meal kit, which can be applied to measure a solid or semisolid gastric mobility. Therein, the albumin of egg powder of the kit is coagulated into a solid form with an isotope tracer at more than 75° C. and the isotope tracer is well incorporated into the food product.  
         [0006]     The present invention also provides a rapid test method with low cost for a gastric emptying measurement, comprising the following steps:  
         [0007]     (a) Rapidly constituting a solid test meal, comprising a dry mix, an isotope tracer (such as a  13 C glycine, a  14 C glycine, a Tc-99 m phytate, a Tc-99 m-sulfur colloid, or a Tc-99 m DTPA) and water, by mixing the dry mix, the isotope tracer and the water and cooking the test meal in 9 minutes.  
         [0008]     (b) Collecting breath samples from the patients before administering the test meal to the patient.  
         [0009]     (c) Orally administering the solid meal in 10 minutes. The Isotope tracer is not adsorbed or metabolized in the stomach, since the isotope tracer is well incorporation in test meal and is chemically stable in the gastric juice.  
         [0010]     (d) Collecting breath samples from the patients per 15 minutes for four hours after administering the test meal to the patient.  
         [0011]     (e) If the isotope tracer is a  13 C glycine or a  14 C glycine, measuring the amount of  13 CO 2  or  14 CO 2  by a carbon isotope breath test to determine the gastric half emptying time of the patient. If the isotope tracer is a Tc-99 m phytate, a Tc-99 m sulfur colloid, or a Tc-99 m DTPA, measuring the gamma count around stomach by a gamma-camera to determine the gastric half emptying time of the patient.  
         [0012]     In the preferred embodiment, the isotope tracer is labeled with a  13 C glycine, a Tc-99 m phytate, a Tc-99 m sulfur colloid, a Tc-99 m DTPA or a  14 C glycine. A  13 C glycine could be a crystal, a capsule, a tablet, a granule or a solution. Because of its small molecular weight, its cost is lower than that of a  13 C octanoic acid. And, because of its water solubility, the rate of adsorption and metabolism is very fast. By incorporating an isotope tracer of a  13 C glycine, a Tc-99 m phytate, a Tc-99 m sulfur colloid, a Tc-99 m DTPA or a  14 C glycine with different test meals, a gastric emptying time could be rapidly measured by a  13 C or  14 C carbon dioxide breath test or scintigraphy. The test meal obtains several advantages which include an easy preparation, a standardization over the composition and the calorie content, a rapid adsorption and metabolism for a rapid test, a well chemical stability, and a water solubility, comprising a homogeneous dry mix and an isotope tracer provided separately to easily obey the FDA regulations and to get a longer shelf-life. In addition, using fructose as an alternative to sucrose containing formulation is preferable to the diabetes individuals who are often the cases for gastric disorders. In the present invention, the meal components are constituted and cooked on site prior to administering the test. On site preparation of the pre-packaged test meal reduces possibilities on the variability associated with the storage of a pre-cooked meal. This formulation also provides commercial advantages, such as that a dry mix has a longer shelf life and requires no special handling.  
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0013]     The present invention will be better understood from the following detailed descriptions of the preferred embodiments according to the present invention, taken in conjunction with the accompanying drawings, in which  
         [0014]      FIG. 1  is a view showing a kit for a gastric emptying measurement according to the present invention;  
         [0015]      FIG. 2  is a view showing isotope tracer retention in a solid phase of a test meal according to the present invention;  
         [0016]      FIG. 3  is a view showing the principle of a  13 C (carbon-13) glycine breath test according to the present invention;  
         [0017]      FIG. 4  is a view showing an in crease in number of a  13 C atom over a baseline in breath after ingestion according to the present invention;  
         [0018]      FIG. 5  is a view showing a  13 C exhaled rate in breath after ingestion according to the present invention;  
         [0019]      FIG. 6  is a view showing a cumulative  13 C-atom excess over a baseline in breath after ingestion according to the present invention;  
         [0020]      FIG. 7  is a view showing a  13 CO 2  coefficient variance of the test meal without isotope tracer oral administered according to the present invention;  
         [0021]      FIG. 8  is a view showing a between-day reproducibility of a solid gastric emptying measurement for the same subject according to the present invention; and  
         [0022]      FIG. 9  is a view showing a composition of a dry mix according to the present invention.  
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0023]     Please refer to  FIG. 1  and  FIG. 2 , which are views showing a kit for a gastric emptying measurement and isotope tracer retention in a solid phase of a test meal, according to the present invention, where isotope tracer retention percentage is obtained in  FIG. 2  in vitro gastric digest at pH 2.3 to imitate the gastric condition after administering the test meal. As shown in  FIG. 1 , the kit comprises a dry mix  1 , which is shipped in a foil, an isotope tracer  2  and a plurality of collecting tubes  3 . A standardized recipe is provided to clinicians in the test meal, which has fixed proportions of carbohydrate, protein, and fat. The raw ingredients in the test meal include a lyophilized egg flour. The characteristic is that the isotope tracer  2  is coagulated with albumin of the egg flour into a solid form at more than 75° C., which means the isotope tracer is well incorporated into a food product. More than 90% of the isotope tracer is retained in a mimic gastric fluid at 35˜39° C. for three hours. The isotope tracer  2  is a  13 C glycine, a  14 C (carbon-14) glycine, a Tc-99 m phytate, a Tc-99 m sulfur colloid or a Tc-99 m DTPA (diethyl-triamine-pentaacetic acid). More than 93% of the  13 C glycine is retained in a mimic gastric fluid at 35˜39° C. for 4 hours. More than 98% of the Tc-99 m phytate is retained in a mimic gastric fluid at 35˜39° C. for 4 hours. More than 90% of the Tc-99 m DTPA is retained in a mimic gastric fluid at 35˜39° C. for 3 hours The dry mix  1  comprises egg powder (7.4%), all purpose flour (19.6%), glutinous rice powder (3.9%), whole milk powder (35.7%), levulose (fructose) flour (8%), foaming powder (3%), cream powder (22%), cream fragrance powder (0.2%), and salt (0.2%), having a most preferred calorie of about 289.5±12.5 kcal. The test meal is standardized in a format, for example a format of a muffin or a semisolid soup. Criteria on format selection are concerning convenience, palatability, stable incorporation of the isotope tracer, and capability on being amended on the standardization for the measurement of a gastric emptying. Furthermore, fructose instead of sucrose is preferably offered to patients having diabetes, who are often the cases with gastric disorders. Glycine is a smallest amino acid, so that it has the fastest adsorption and metabolism rate. The present invention is capable of getting a half-gastric emptying time in a shorter period, is cost low, and has a well chemical stability. The chemical stability of the dry mix  1  and stable isotope tracer last more than 2 years.  
         [0024]     The present invention costs low and provides a rapid gastric emptying measurement by a carbon breath test or a scintigraphy, comprising the following steps:  
         [0025]     (a) Rapidly constituting a solid test meal comprised with the dry mix  1 , the isotope tracer  2  and water, by mixing them up, and then cooking the test meal in 9 minutes. If the isotope tracer  2  is a  13 C glycine or a  14 C glycine, then a carbon breath test is used to determine a half-gastric emptying time; if the isotope tracer  2  is a Tc-99 m phytate, a Tc-99 m-sulfur colloid, or a Tc-99 m DTPA, then a scintigraphy is used to determine the half-gastric emptying time.  
         [0026]     Please refer to  FIG. 3 , which is a view showing the principle of a  13 C glycine breath test according to the present invention. As shown in the figure, the test meal  10  is taken by mouth  11  and is digested in the stomach  12 ; the  13 C glycine (NH 2 CH 2   13 COOH) is metabolized in the liver  13  (H 13 CO 3   − +metabolites); a gas  16  of  13 CO 2  is obtained in lung  14 ; and, then, the gas  16  is exhaled by the mouth  15  to be collected for a test.  
         [0027]     (b) Collecting breath samples from the patients before administering the test meal to the patient.  
         [0028]     (c) Oral administering the solid meal with 100 mL (milliliter) of water in 10 minutes.  
         [0029]     (d) Collecting breath samples each collected from the patient at every 15 minutes during four hours after administering the test meal to the patient.  
         [0030]     (e) Measuring a carbon isotope ratio by a mass spectrometer or an infrared spectrometer, if the isotope tracer is a  13 C glycine, to determine the gastric ha If emptying time of the patient. As shown in  FIG. 4 , the X-axis is sampling time after oral administering the breath meal; and the Y-axis is the increase amount of a  13 C/ 12 C ratio. So,  FIG. 4  shows a curve of an increase amount of  13 C/ 12 C ratio. In a medical examination, the isotope ratio of  13 C/ 12 C is expressed as δ 13 C according to the following equation:  
           δ   13     ⁢   C     =           R   S     -     R   PDB         R   PDB       ×   1000   ⁢     (     per   ⁢           ⁢   mil     )           
 
 , where the R S  is the isotope ratio of  13 C/ 12 C in an unknown sample and the PDB is a primary standard whose ratio of  13 C/ 12 C is 0.0112372. 
 
         [0031]     (f) Converting results obtained from  13 CO 2  breath tests at (e) to %  13 C to be expressed in a percentage of an administered dose of  13 C recovered per hour (i.e. a %  13 C recovery/hr or a %  13 C dose/hr), and to be expressed in a cumulative percentage of the administered dose of  13 C recovered over time (i.e. a %  13 C cumulative dose). The shape of the curve of the %  13 C dose/hr shows the dynamics of the process. It reflects the rate at which the process occurs. The %  13 C cumulative dose, derived numerically from the %  13 C dose/hr data, informs about the global process (as shown in  FIG. 6 ).  
         [0032]     (g) A non-linear regression analysis is performed on the originally measured data to obtain parameter values of the rate at which stomach empties.  
         [0033]     The dry mix  1  uses fructose as an alternative to sucrose containing formulation, where the fructose is preferable to diabetes individuals for long-term follow-up examinations. Besides, the  13 C abundance of mix  1  (δ 13 C=−25.5 per mil) is close to the baseline of human breath, which indicates the test meal prepared without isotope tracer did not cause apparent fluctuation of  13 C/ 12 C ratio in breath test. (CV=0.27% in 4 hr after administering to the patients) (see  FIG. 7 ). The dry mix  1  and the  13 C glycine  2  are provided separately for a longer term of storage, which minimize the concerns on stability and FDA regulation. They mimic a true meal and are convenient for palatability, easy preparation, good stability and good precision. The  13 C glycine  2  combined with the dry mix  1  could be oral administered through stomach to small intestine for a rapid adsorption and a rapid metabolism in liver. The present invention significantly improves current methodologies because it is not limited by the availability of gamma cameras at clinical sites. It is more convenient than a scintigraphic test, because the patient do not have to remain motion less under the expensive instrument. It allows more people to take the test simultaneously. The between-day CV for the same individual is below 10%, which significantly improves the reproducibility of the solid gastric emptying measurement (as shown in  FIG. 8 ). In addition, the followings are examples of preferred embodiments in detail:  
       EXAMPLE 1  
     A Test Meal of a Solid Gastric Emptying Measurement  
       [0034]     The composition of the dry mix  1  is prepared according to  FIG. 9 . The dry mix  1  is packed in an aluminum foil and is standardized in weight and calorie. The weight is 70±3 grams and the total calorie is 289.5±12.5 kcal. The  13 C/ 12 C isotope ratio measured with a mass spectrometer is −25.5±0.2 per mil, which is close to the  13 C/ 12 C isotope ratio −24.6±1.3 per mil of the exhaled human breath with a general daily diet and so indicates that the kit&#39;s formula and composition are close to a general daily diet (Gut 2002; 51, suppl III, A109.) (Amer J Clin Nutr 1980; 33, 2375.). The shelf-life for the dry mix  1  stored at a room temperature is at least one year and that for a  13 C glycine is more than 5 years. The  13 C glycine solid test meal is prepared by putting the dry mix  1  in a container to be mixed with a dissolving  13 C glycine (50 mg (milligram)/50 mL); and then is stirred to be battered and is instantaneously coagulated at more than 75° C. for 5 minutes by a waffle iron to produce a test meal in a muffin format. The Tc-99 m phytate solid test meal is prepared by putting the flour of the dry mix  1  in a container to be mixed with 1 mCi (millicurie) of a Tc-99 m phytate and 50 mL of water, and then is stirred to be battered and is instantaneously coagulated at more than 75° C. for 5 minutes by a waffle iron to produce a test meal in a muffin format. The Tc-99 m DTPA solid test meal is prepared by putting the flour of the dry mix  1  in a container to be mixed with 1 mCi of a Tc-99 m DTPA and 50 mL of water; and then is stirred to be battered and is instantaneously coagulated at more than 75° C. for 5 minutes by a waffle iron to produce a test meal in a muffin format.  
       EXAMPLE 2  
     An In-Vitro Gastric Simulation  
       [0035]     To assess the extent of  13 C glycine retention in the solid phase of the test meal, a simulated gastric digest is made. A muffin is prepared as described in the section above with 100 mg of a  13 C glycine mixed with the dry mix  1  and water. After chewing the test meal, it is put into a semi-permeable membrane (Spectra/PorMembrane MWCO 3,500, 54 mm×150 mm) incubated and shook with a simulated gastric juice (2 g (gram) of sodium chloride; 3.2 g of pepsin; and, 7 mL of HCl in 1000 mL, pH 1.2) at 37±2° C. having different time intervals. 5 mL aliquot of the liquid phase were removed at regular 60 min intervals, centrifuged and aliquots of the supernatants removed for C-13 glycine quantification with Liquid Chromatography/Mass Spectrometry. Results are then expressed as a percentage, P %, of the initial amount of the  13 C glycine added. And, (100−P %) means an incorporation percentage of the  13 C glycine in the test meal. The results (as shown in  FIG. 2 ) show more than 93% of the  13 C glycine is incorporated in the test meal after 4 hours.  
         [0036]     To assess the extent of Tc-99 m phytate retention in the solid phase of the test meal, a simulated gastric digest is made. A muffin is prepared as described above with 1 mCi of a Tc-99 m phytate, which is equivalent to 156.25 μg (microgram) with a specific activity of 10.06 mCi/μmol (μmol, micromolar) mixed with the dry mix  1  and water. After chewing the test meal, it is put into a semi-permeable membrane (Spectra/PorMembrane MWCO 3,500, 54 mm×150 mm) incubated and shook with a simulated gastric fluid (2 g of sodium chloride, 3.2 g of pepsin and 7 mL of HCl in 1000 mL, pH1.2) at 37±2° C. having different time intervals. 5 mL aliquot of the liquid phase were removed at regular 60 min intervals, centrifuged and aliquots of the supernatants removed for liquid scintillation counting Results are then expressed as a percentage, P %, of the initial amount of a radioactivity added. And, (100−P %) means an incorporation percentage of the Tc-99 m phytate in the test meal. The results (as shown in  FIG. 2 ) show more than 98% of the Tc-99 m phytate is incorporated in the test meal after 4 hours.  
         [0037]     To assess the extent of Tc-99 m DTPA retention in the solid phase of the test meal, a simulated gastric digest is made. A muffin is prepared as described above with 1 mCi of a Tc-99 m DTPA, which is equivalent to 110.22 μg with a specific activity of 4.54 mCi/μmol, mixed with the dry mix  1  and water. After chewing the test meal, it is put into a semi-permeable membrane (Spectra/PorMembrane MWCO 3,500, 54 mm×150 mm) incubated and shook with a simulated gastric fluid (2 g of sodium chloride, 3.2 g of pepsin and 7 mL of HCl in 1000 mL, pH1.2) at 37±2° C. having different time intervals. 5 mL aliquot of the liquid phase were removed at regular 60 min intervals, centrifuged and aliquots of the supernatants removed for liquid scintillation counting. Results are then expressed as a percentage, P %, of the initial amount of a radioactivity added. And, (100−P %) means an incorporation percentage of the Tc-99 m DTPA in the test meal. The results (as shown in  FIG. 2 ) show more than 87% of Tc-99 m DTPA is incorporated in the test meal after 4 hours.  
       EXAMPLE 3  
     The Stability and Suitability of a Test Meal for the Solid Gastric Emptying Measurement  
       [0038]     To perform a gastric emptying test, a baseline sample of breath is collected using a septum capped glass tube in the morning after an overnight fast; and then is analyzed to obtain a baseline δ 13 C level. The blank solid test meal is prepared by putting the flour of the dry mix  1  along with water in a container; and then is stirred to be battered and is instantaneously coagulated at more than 75° C. for 5 minutes by a waffle iron to produce a blank test meal in a muffin format. The patient then administered the blank test meal along with 100 mL water within 10 minutes. The breath samples are collected with a 15-minute interval for 4 hours and analyzed using an isotope ratio mass spectrometer and are plotted into  FIG. 7 . The X-axis of  FIG. 7  is a sampling time and the Y-axis of  FIG. 7  is the  13 C/ 12 C isotope ratio (δ 13 C). The curve shows the variation of the breath samples is only 0.27%. It means the fluctuation of the baseline of the breath tests for the dry mix  1  of the test meal is very low and stable; and do not affect the results of the breath tests. The  13 C abundance of dry mix  1  was determined to be −25.5±0.2 per mil with an isotope ratio mass spectrometer, which closely approximates the  13 C abundance of fasting breath CO 2  from the patients. Besides, the low baseline fluctuation indicates it will not alter the CO 2  abundance in breath test (Am. J. Clin. Nutr. 33:2375˜2385, 1980).  
       EXAMPLE 4  
     The Quantification of a Half-Emptying Time and Lag Phase Time  
       [0039]     A test meal is prepared by putting the dry mix  1  along with a dissolving  13 C glycine (50 mg/50 mL) in a container; and then is stirred to be battered and is instantaneously coagulated at more than 75° C. for 5 minutes by a waffle iron to produce a test meal in a muffin format. The test meal is administered after an overnight fast along with 100 mL of water within 10 minutes. The first one of the breath samples is collected before the test meal is administered so that a baseline is obtained. And the rest of the breath samples are collected with an 15-minute intervals during 4 hours after the test meal is administered. A measurement can be conveniently done using an isotope ratio mass spectrometer. The results obtained are then expressed in a δ 13 C value ( 13 C/ 12 C).  FIG. 6  shows a cumulative %  13 C dose excretion curve of the breath tests, which resembles the reversed retention curve. The  13 CO 2  excretion parameters are derived from the chi-square distribution in statistics and the equation is expressed as follows. 
 
 CD=m (1− e   −kt ) β 
 
 , where CD is the cumulative percentage of the administered dose; t is the time; and, m is the total cumulative percentage of the dose recovered. 
 
         [0040]     A non-linear regression analysis is performed on the originally measured data to obtain values of the m, k, and β for each individual breath test.  
         [0000]     A. Half Emptying Time:  
         [0041]     The half emptying time is calculated by making CD equal to m/2 in the CD equation:  
         t     1   2       =       (     -     1   k       )     ⁢     ln   (     1   -     2     -     1   β           )           
 
 B. Lag Phase: 
 
         [0042]     The lag phase for the breath test has been defined, which is expressed as follows: 
 
 t   lag =1/k ln β
 
       EXAMPLE 5  
     An Example of a Test Calculation  
       [0000]    
       
          (1) Patient: X  
          (2) Weight (W): 60 kg  
          (3) Height (H): 164 cm  
          (4) Body Surface Area, BSA: 
 
(W 0.5378 ×H 0.3964 )×0.024265=1.6566 (unit: m 2 , meter square) 
 
 BSA =(W 0.5378 ×H 0.3964 )×0.024265, 
 
           which is calculated according to the formula of Haycock et al. (J. Pediatr., 93, 62-66, 1978.)  
           W means weight (in kg, kilogram)  
           H means height (in cm, centimeter)  
          (5)  
           CO   2     ⁢           ⁢   production     =       300   ⁢     (     mmol   ⁢     /     ⁢       m   2     ·   hr       )     ×     BSA   ⁡     (     m   2     )         =     497   ⁢     (     mmol   ⁢     /     ⁢   hr     )             
 
           (mmol, millimolar; m, meter)  
          (6) substrate ( 13 C-glycine) mg administered=50 mg  
          (7) %  3 C-substrate=99 atom %  
          (8) molecular weight of  13 C-glycine=76.06 mg/mmol  
          (9) n=1 (only the carboxyl group of glycine is  13 C labeled)  
          (10) measuring  13 C/ 12 C of breath samples using an isotope ratio mass spectrometer (δ 13 C, per mil)  
          (11) obtaining a Δδ 13 C of breath samples at each sampling time by subtracting δ 13 C collected at time zero from δ 13 C at each sampling time. Results of Δδ 13 C are shown in  FIG. 4 .  
          (12) The Δδ 13 C value obtained by the mass spectrometric analysis is converted to %  13 C; and results on  13 CO 2  breath tests are expressed in percentage of the administered dose of  13 C recovered per hour (i.e. %  13 C recovery/hr or %  13 C dose/hr).  FIG. 5  represents a  13 CO 2  excretion (in %  13 C dose/hr) in a course of time. The shape of the %  13 C dose/hr curve shows the dynamics of the process. It reflects the rate at which the process occurs (delayed, accelerated, with or without a lag phase). The %  13 C dose/hr is calculated by the following equation Eq. 1:  
                 %   13     ⁢   C   ⁢           ⁢   dose   ⁢     /     ⁢   hr     =           mmol   13     ⁢   C   ⁢           ⁢   excess   ⁢           ⁢   in   ⁢           ⁢   breath   ⁢           ⁢     (   a   )           mmol   13     ⁢   C   ⁢           ⁢   excess   ⁢           ⁢   administered   ⁢           ⁢     (   b   )         ×   100             Eq   .           ⁢   1             
        The definition of mmol  13 C excess in breath (a) and mmol  13 C excess administered (b) were shown below:  
                       mmol   13     ⁢   C   ⁢           ⁢   excess   ⁢           ⁢   in   ⁢           ⁢   breath     =       (           %   13     ⁢     C   1       -       %   13     ⁢     C     t   0           100     )     ×     CO   2     ⁢           ⁢   production       ⁢     
       ⁢   %13   ⁢   Ct     =         (         δ   ⁢           ⁢   t     1000     +   1     )     ×   0.0112372         (       (         δ   ⁢           ⁢   t     1000     +   1     )     ×   0.0112372     )     +   1               (   a   )             
            0.0112372 is the ratio of  13 C/ 12 C of PDB     %  13 C t  and %  13 C t     0   : the concentration of  13 C at time t and t 0  (i.e. time zero)     δt=δ 13 C value at time t (%  13 C t −%  13 C t     0   ) is also called “ 13 C atom percent excess” 
                 mmol   13     ⁢   C   ⁢           ⁢   excess   ⁢           ⁢   administered     =       (           %   13     ⁢     C     substr   .         -       %   13     ⁢     C     t   0           100     )     ×     m   M     ×   n             (   b   )             
    %  13 C substr. =%  13 C present in substrate     M=molar mass of substrate     m=amount of substrate     n=number of atoms,  13 C-labelled    
           
     
          (13) The %  13 C cumulative dose is derived numerically from the %  13 C dose/hr data and is calculated from the following Eq. 2, which informs about the global process. The  13 C cumulative excretion is shown in  FIG. 6 .  
                 %   13     ⁢     C         cumul   .   dos     ⁢           ⁢     t   i       +   1         =         %   13     ⁢     C       cumul   .   dose     ⁢           ⁢     t   i           +       (           %   13     ⁢     C     dose   ⁢           ⁢     t   i           +       %   13     ⁢     C     dose   ⁢           ⁢     t     i   +   1               2     )     ×     1   n                 Eq   .           ⁢   2             
        n=number of samples per hour     n=4, if a breath sample is taken every 15 minutes     t i =time i    
     
       
     
         [0071]     The numerical calculation is given as follows in detail:  
                                                                     Sampling                       time   δ 13 C   Δδ 13 C   %  13 C       (min)   (per mil)   (per mil)   (dose/hr)   %  13 C cumul.dose                                  0   −21.6   0   —   —       15   −20.3   1.3   1.10377   0.13797       30   −18.3   3.3   2.80151   0.61787       45   −17.0   4.6   3.90500   1.45618       60   −16.0   5.6   4.75382   2.53853       75   −15.0   6.6   5.60262   3.53309       90   −15.6   6.0   5.09334   5.17009       105   −14.7   6.9   5.85726   6.53892       120   −14.5   7.1   6.02701   8.02445       135   −13.7   7.9   6.70603   9.61608       150   −14.7   6.9   5.85726   11.18649       165   −15.4   6.2   5.26310   12.57654       180   −16.4   5.2   4.41430   13.78622       195   −17.3   4.3   3.65035   14.79430       210   −17.3   4.3   3.65035   15.70689       225   −18.0   3.6   3.05617   16.54521       240   −18.6   3.0   2.54685   17.24559                  
    (14) Mathematically analyzing the  13 CO 2  excretion curves with a Sigma plot software. The cumulative %  13 C dose excretion curve of the breath test (as shown in  FIG. 6 ) is described as an equation: CD=m(1−e −kt ) β ; and, m=22.844, k=0.0101 and β=2.8256 are obtained. All of these parameters were determined by a non-linear regression analysis. The half emptying time is calculated by making CD equal to m/2 in the CD equation and being defined by  
               t     1   2       =       (     -     1   k       )     ⁢     ln   ⁡     (     1   -     2     -     1   β           )                 Eq   .           ⁢   3             
     . The half-emptying time is equal to 151.0 minutes, which is calculated by entering these parameters of k and β into the equation of Eq. 3. The lag phase for the breath test is expressed as t lag =1/k ln β (Eq. 4). The emptying delayed time is equal to 102 minutes, which is calculated by entering these parameters of k and β into the equation of Eq. 4.    
 
       EXAMPLE 6  
     A Between-Day Reproducibility of the Solid Gastric Emptying Measurement for the Same Subject  
       [0074]     The reproducibility of the solid gastric emptying measurement is investigated by thirty-five volunteers within a one-week period using a  13 C breath test. The dry mix  1 , water and a  13 C-glycine are mixed thoroughly. The mix is cooked exactly as directed, and is coo led to a room temperature. The patients arrive at the clinician&#39;s facility after an overnight fast and a baseline sample of CO 2  is collected from the patients. The test meal is administered with 100 mL of water. The patients remain within a certain area throughout the test. Samples are continuously collected with a 15-minute interval for 4 hours. The appearance of label is measured appropriately. The  13 CO 2  excretion curves are mathematically analyzed using a non-linear regression method to get the half-emptying time (t 1/2 ) and the lag phase time (t lag , emptying delayed time). The between-day coefficient variance is below 10%, either for t lag  or t 1/2  (as shown in  FIG. 8 ).  
         [0075]     To sum up, the present invention relates to a  13 C-glycine kit for solid or semisolid gastric emptying measurement. The test meal is made in a muffin form by a quick coagulation of albumin with the other constituents in the dry mix  1  together with the  13 C-glycine cooked at more than 75° C. The incorporation of the isotope tracer  2  mixed into the muffin and the characteristics of the  13 C-glycine are the major causes for a good precision and stability during the gastric emptying measurement. The measurement is finished soon even including the preparation of the test meal. Besides, the test meal is easy for a quick preparation. The advantages also include the low cost of the  13 C-glycine, a long shelf-life of the  13  C-glycine, and the palatability provided. The isotope tracer and the dry mix are provided separately, which makes it easy for the quality and quantity control and is easy to obey the FDA regulations. Furthermore, fructose is chosen as an alternative to sucrose containing formulation is preferred for the diabetes which is often the case for a gastric disorder. So, the present invention allows an accurate standardization and a more convenient measurement for gastric emptying results.  
         [0076]     The preferred embodiments herein disclosed are not intended to unnecessarily limit the scope of the invention. Therefore, simple modifications or variations belonging to the equivalent of the scope of the claims and the instructions disclosed herein for a patent are all with in the scope of the present invention.