TW201536353A - Adsorbent capable of lowering uremia in human body - Google Patents

Abstract

The present invention provides an adsorbent capable of lowering uremia in human body, which includes poly-acrylonitrile activated carbon fiber with the following characteristics: (1) the average diameter is 5-30 [mu]m; (2) the BET specific surface area is greater than 390 m2/g; (3) the total acid base is greater than 1.2 meq/g or the total alkaline base is greater than 1 meq/g. The adsorbent has a relatively high adsorbing capability for the uremia precursor but a relatively low adsorbing capability for the normal enzyme inside the intestine. As a result, the uremia adsorbent of this invention is able to effectively alleviate the deterioration of kidney function and thus can be used as treatment agent or prevention agent for kidney diseases.

Description

An adsorbent that reduces urinary toxins in the body

The present invention relates to an oral substance for the treatment or prevention of kidney diseases, and more particularly to an adsorbent capable of reducing urinary toxins in the body, for reducing urinary toxins in an individual and slowing the deterioration of renal function.

The metabolic waste excreted by the kidneys is known as urinary toxin, and the concentration of urinary toxin in the serum can be used as an indicator of renal function. A urinary toxin: indoxyl sulfate is considered to be one of the main causes of the deterioration of chronic kidney disease. The process of producing phenolic phenol is that the bacteria in the intestine metabolize Tryptophan from food to Indole, and then metabolize it to the sulphate in the liver, and then excreted through the kidney. When kidney function declines, sulphuric acid phenol and other urinary toxins, such as creatinine and blood urea nitrogen, accumulate in the body, eventually causing kidney failure. Patients with kidney failure must undergo kidney transplantation or dialysis to maintain their lives. However, kidney transplantation is not easy; dialysis treatment is easy to be accompanied by complications such as vascular embolism. Therefore, if the cumulative amount of urinary toxin in the body can be reduced in the early stage of renal function decline, the rate of renal function decline can be slowed down, and the incidence of dialysis treatment can be reduced.

Excellent to reduce the urinary toxin adsorbent after oral administration into the intestine should have high adsorption capacity for urinary toxin precursors such as leaching, but has low adsorption force to intestinal enzyme proteins such as lipase, so selective The adsorption function of the adsorbent can reduce the accumulation of urinary toxins in the body without disturbing the normal function of the gastrointestinal tract. Conventional reduction of urinary toxin adsorbents for urinary toxins The precursor has poor adsorption and does not selectively adsorb the function. Therefore, the conventional adsorbent has a limited effect of slowing the decline of renal function and cannot avoid disturbing the normal function of the gastrointestinal tract.

The object of the present invention is to provide a urinary toxin adsorbent which can reduce the urinary toxin precursor in the gastrointestinal tract without affecting the enzyme protein in the intestinal tract, reducing the rate of accumulation of urinary toxin in the body, and slowing the decline of renal function. Rate, reducing the incidence of dialysis treatment.

For the above purposes, the present invention can reduce the in vivo uremic toxin adsorbent comprising: polyacrylonitrile activated carbon fiber having the following characteristics: (1) an average diameter of 5 to 30 μm , and (2) a BET specific surface area of 390 m ² Above /g, (3) total acid groups greater than 1.2 meq/g or total basic groups greater than 1 meq/g. The conventional adsorbent of the invention has high adsorption force to the uremic toxin precursor, and has low adsorption force to the intestinal enzyme protein, can effectively reduce the accumulation of urinary toxin in the body, and does not interfere with the gastrointestinal tract. Normal function, can be used as a therapeutic agent for kidney disease to slow down the rate of renal function decline, or as a preventive agent for kidney disease to reduce the incidence of dialysis treatment.

10‧‧‧Polyacrylonitrile activated carbon fiber

20‧‧‧ kidney skein

22‧‧‧Tubules

24‧‧‧denatured or regenerated tubular

Fig. 1 is an electron micrograph of a polyacrylonitrile activated carbon fiber contained in Example 1 of the present invention.

Fig. 2 is a graph showing in vitro test results of the adsorption rates of the introduced and lipolytic enzymes of Examples 1 to 5 of the present invention and Comparative Examples.

Figure 3 shows the changes in the concentration of sulphate-derived phenol in the serum of normal mice (WT), control mice (Nep), and experimental mice (Nep-ACF) in the in vivo test.

Figure 4 shows the changes in the concentration of urea nitrogen in the serum of normal mice (WT), control rats (Nep), and experimental mice (Nep-ACF) in the in vivo test.

Figure 5 shows the normal test (WT), control mouse (Nep), and experimental mouse (Nep-ACF) in the in vivo test. Changes in serum creatinine concentration.

Figure 6 is a micrograph of the kidneys of normal mice.

Figure 7 is a graph of the kidney staining of control mice.

Fig. 8 is a graph showing the staining of kidneys of the experimental mice fed Example 1.

The following examples are used to illustrate the technical features and effects of the present invention. The characteristics mentioned in the respective examples were measured by the following methods.

The average diameter and length are calculated using a scanning electron microscope (for example, S-4800 manufactured by Hitachi, Japan).

The BET specific surface area and the percentage of micropores (less than 2 nm in diameter) / mesopores (2-50 nm in diameter) / macropores (more than 50 nm in diameter) are based on a high resolution specific surface area analyzer (for example, ASAP2020 manufactured by Micromeritics, USA) for porous materials. Analysis.

Density is measured by true density method. The sample is placed in a confined space to evacuate, the water in the pore is removed, and then the helium is refilled. The backfill gas is calculated to determine the true volume and weight of the sample. True density.

The total acidity was determined by adding 1 g of sample to 50 ml of 0.05 N sodium hydroxide (NaOH), shaking at room temperature for 48 hours, filtering and titrating to neutral with 0.05 N hydrochloric acid (HCl) to calculate the amount of hydrochloric acid used for titration. The total acidic base (meq/g) per gram of sample can be calculated. The total basic basis is determined by adding 1 g of sample to 50 ml of 0.05 N hydrochloric acid, shaking at room temperature for 24 hours, filtering and titrating to neutral with 0.05 N sodium hydroxide, and calculating the amount of sodium hydroxide used for titration. Total base (meq/g) per gram of sample.

The in vitro adsorption test of the leaching and lipolytic enzymes was prepared by preliminarily preparing a solution for simulating the intestinal environment, which contained 100 ppm of sputum, 100 ppm of lipolytic enzyme and 5% of bile acid. Take the simulation 10 ml of the solution in the intestinal environment was added to a sample of 0.01 g, and the concentration of the lead and lipolytic enzyme remaining in the solution was measured after the action at 37 ° C for 3 hours. The adsorption rate is 100 - (residual concentration / original concentration) * 100.

Food safety was performed by feeding BALB/c mice at a daily dose of 5% for 30 days, and the survival rate, behavior, and color of excreta were observed.

The urinary toxin precursor biosorption test used three male Sprague-Dawley rats weighing 200-250 g, which were subdivided into normal mice (WT), control mice (Nep) and experimental mice (Nep-ACF). Normal rats were resected without nephrectomy and fed with normal feed. The control rats were surgically removed from 5/6 kidneys and fed with normal feed. The rats were surgically resected with 5/6 kidneys and fed with 5% of the adsorbent of the present invention. feed. After 10 weeks of feeding, serum concentrations of lead phenol, urea nitrogen and creatinine were measured weekly.

After the renal histopathological diagnosis was completed, the kidney tissue sections of the rats were prepared and stained with hematoxylin and eosin stain (H&E stain). The extent of damage in renal histopathological diagnosis was determined according to the method described in Shackelford et. al., Toxicologic Pathology, vol. 30, no. 1, pp 93-96, 2002, in a fixed range of renal tissue, with or without tubular degeneration. Or regeneration, and graded according to the degree of degeneration or regeneration or the number of occurrences, can be divided into: first level (very few, <1%), second level (slight, 1-25%), third level (middle Degree, 26-50%), fourth (moderately severe, 51-75%) and fifth (serious, 76-100%).

<Example 1>

The present embodiment provides an adsorbent capable of reducing urinary toxins in the body, the adsorbent is coated with a polyacrylonitrile activated carbon fiber in a capsule, and the polyacrylonitrile activated carbon fiber is made of polyacrylonitrile carbon fiber cloth (Panex ^® 30, Zoltek Companies, Inc.) was formed by oxidation in an aqueous carbon dioxide gas at 1000 ° C for 5 minutes and then ground. The polyacrylonitrile carbon fiber cloth was composed of 90% by weight of polyacrylonitrile plus 10% by weight of Rayon or a pitch pitch. The activated carbon fiber has an average diameter of 7.6 μm, a BET specific surface area of 964 m ² /g, a density of 2.13 g/m ³ , a micropore/mesopore/macroporous percentage of 22/78/0%, and a length of 23.2±6.9 μm. The total acidic group was 1.092 meq/g and the total basic group was 1.30 meq/g. Fig. 1 is the appearance of the activated carbon fiber of the present example.

Figure 2 shows the results of in vitro adsorption test, and Example 1 can adsorb 89.6% of uremia. The precursor is introduced and adsorbs 2.33% of lipolytic enzyme. The results of the food safety test showed that there was no abnormality in the survival rate and behavior of the mice. It was also observed that the color of the excreta was darker. It was inferred that the adsorbent was excreted through the gastrointestinal tract, so the adsorbent was safe to eat.

Figure 3 shows the results of the in vivo adsorption test of sulphuric acid, and the consumption of the adsorbent is only One week later, the concentration of sulphate-derived phenol in the test mouse (Nep-ACF) (1.55 ng/ml) was lower than that in the control mouse (Nep) (2.6 ng/ml). During the ten weeks of consumption, the concentration of sulphate in the experimental mice (Nep-ACF) was lower than that in the control rats (Nep), which proved that the consumption of the sorbent did reduce the sulfate in the rats with renal function decline. The cumulative amount of phenol.

Figure 4 shows the urea nitrogen in vivo adsorption test results, only one week for the adsorbent Thereafter, the urea nitrogen concentration (36 mg/dl) in the test mouse (Nep-ACF) was lower than the urea nitrogen concentration (38 mg/dl) in the control mouse (Nep). After 10 weeks of consumption, the urea nitrogen concentration (30 mg/dl) in the experimental mice (Nep-ACF) was only 8 mg/dl higher than the urea nitrogen concentration (22 mg/dl) in normal mice (WT), but the control mice (Nep) The concentration of urea nitrogen in the body (56 mg/dl) is 34 mg/dl higher than that in normal mice (WT). In other words, the concentration of urea nitrogen in the experimental mice (Nep-ACF) is only the control mouse (Nep). The cumulative concentration of urea nitrogen in the body was 24% (8/34 = 0.24), which proved that the consumption of the adsorbent could actually reduce the accumulation of urea nitrogen in rats with renal function decline.

Figure 5 shows the results of creatinine in vivo adsorption test, eating the adsorbent only for one week Thereafter, the creatinine concentration (0.6 mg/dl) in the test mouse (Nep-ACF) was lower than the creatinine concentration (0.75 mg/dl) in the control mouse (Nep). After 10 weeks of consumption, the creatinine concentration (0.61 mg/dl) in the experimental mice (Nep-ACF) was only 0.25 mg/dl higher than the creatinine concentration (0.36 mg/dl) in normal mice (WT), but the control was The concentration of creatinine (0.86 mg/dl) in the mouse (Nep) was 0.5 mg/dl higher than that in the normal mouse (WT). In other words, the cumulative concentration of creatinine in the mouse (Nep-ACF) was only 50% (0.25/0.5 = 0.5) of the cumulative concentration of creatinine in the control mouse (Nep) demonstrated that consumption of the adsorbent did reduce the accumulation of creatinine in rats with impaired renal function.

Figures 6 to 8 show the results of the degree of damage to rat kidney tissue. Figure 6 shows The normal mouse (WT) is shown to have a normal kidney spheroid 20 and a renal tubule 22. Figure 7 shows that the control mouse (Nep) has a degenerated or regenerated tubular tube 24 with a third degree of damage. Figure 8 shows that the experimental mouse (Nep-ACF) has degenerated or regenerated renal tubules 24 with a second degree of damage. Comparison of Figures 6 to 8 demonstrates that after 10 weeks of consumption of the adsorbent, the degree of renal damage in rats with impaired renal function can be reduced.

Based on the above results, the adsorbent provided in the first embodiment has a urine toxin. Precursors have higher adsorption capacity, lower adsorption capacity to enzymes in the intestinal tract, food safety, lowering the concentration of urinary toxins in the body, and reducing the degree of kidney damage. Therefore, in the first embodiment, the rate of renal function decline can be slowed down and the incidence of dialysis treatment can be reduced without disturbing the normal operation of the gastrointestinal tract.

<Comparative example>

The comparative example uses a commercially available food grade activated bamboo charcoal powder as an adsorbent, and the properties of the active bamboo carbon powder are as follows: irregular granular shape, average particle diameter of 2.9±1.4 μm, BET specific surface area of 329 m ² /g, micro The percentage of holes/mesholes/macropores was 15.7/83.5/0.7%. Figure 2 shows the results of the in vitro adsorption test of the comparative example, which can adsorb 17.1% of the lead and 23.25% of the lipolytic enzyme, that is, the comparative example has a lower adsorption force on the uremic toxin precursor and has an enzyme in the intestinal tract. Higher adsorption capacity, therefore can not effectively reduce the accumulation of urinary toxins in the body, and will interfere with the normal function of the gastrointestinal tract.

Example 1 has a higher adsorption capacity for the uremic toxin precursor than the comparative example, but The intestinal enzyme protein has a low adsorption capacity. Therefore, the rate of slowing down the renal function can be achieved without disturbing the normal function of the intestine. Further experimental results show that, in addition to the first embodiment, the second to fifth examples listed below have similar effects.

<Embodiment 2>

The adsorbent of this embodiment is coated with a polyacrylonitrile activated carbon fiber in a capsule which is oxidized by a polyacrylonitrile carbon fiber cloth (Panex ^® 30, Zoltek Companies, Inc.) in an aqueous carbon dioxide gas. It was formed at 900 ° C for 20 minutes and then ground. The properties were as follows: average diameter of 9.3 μm, BET specific surface area of 398 m ² /g, density of 1.749 g/m ³ , microporous / mesoporous / giant The percentage of pores was 18/82/0%, the length was 27.1±2.4 μm, the total acid group was 1.559 meq/g, and the total basic group was 0.9 meq/g. The results of the in vitro adsorption test are shown in Fig. 2. In the second embodiment, 75.3% of the induced filaments can be adsorbed, and 6.3% of the lipolytic enzyme is adsorbed, indicating that the second embodiment has a higher adsorption capacity for the uremic toxin precursor. Intestinal enzymes have a lower adsorption capacity.

<Example 3>

The adsorbent of this embodiment is coated with a polyacrylonitrile activated carbon fiber in a capsule which is oxidized by a polyacrylonitrile carbon fiber cloth (Panex ^® 30, Zoltek Companies, Inc.) in an aqueous carbon dioxide gas. It was formed at 900 ° C for 40 minutes and then ground. The properties were as follows: average diameter of 8.6 μm, BET specific surface area of 921 m ² /g, density of 2.043 g/m ³ , microporous / mesoporous / giant The percentage of pores was 21/79/0%, the length was 21.9±1.4 μm, the total acid group was 1.384 meq/g, and the total basic group was 1.26 meq/g. The results of the in vitro adsorption test are shown in Fig. 2. In the third embodiment, 84.7% of the induced filaments can be adsorbed, and 4.4% of the lipolytic enzyme is adsorbed, indicating that the third embodiment has a higher adsorption capacity for the uremic toxin precursor. Intestinal enzymes have a lower adsorption capacity.

<Embodiment 4>

The adsorbent of this embodiment is coated with a polyacrylonitrile activated carbon fiber in a capsule which is oxidized by a polyacrylonitrile carbon fiber cloth (Panex ^® 30, Zoltek Companies, Inc.) in an aqueous carbon dioxide gas. It was formed at 1000 ° C for 20 minutes and then ground. The properties were as follows: average diameter of 6 μm, BET specific surface area of 1244 m ² /g, density of 2.153 g/m ³ , microporous / mesoporous / macroporous The percentage is 18/82/0%, the length is 26.2±2.5 μm, the total acid group is 1.253 meq/g, and the total basic group is 1.685 meq/g. The results of the in vitro adsorption test are shown in Fig. 2. In the fourth embodiment, 84.3% of the induced filaments can be adsorbed, and 8.9% of the lipolytic enzyme is adsorbed, indicating that the fourth embodiment has a higher adsorption capacity for the uremic toxin precursor. Intestinal enzymes have a lower adsorption capacity.

<Embodiment 5>

The adsorbent of this embodiment is coated with a polyacrylonitrile activated carbon fiber in a capsule which is oxidized by a polyacrylonitrile carbon fiber cloth (Panex ^® 30, Zoltek Companies, Inc.) in an aqueous carbon dioxide gas. It was formed at 1000 ° C for 40 minutes and then ground. The properties were as follows: average diameter of 5.6 μm, BET specific surface area of 1494 m ² /g, density of 2.163 g/m ³ , microporous / mesoporous / giant The percentage of pores was 19/81/0%, the length was 22.7±4.5 μm, the total acid group was 1.7 meq/g, and the total basic group was 0.969 meq/g. The results of the in vitro adsorption test are shown in Fig. 2. In the fifth embodiment, 81.2% of the induced filaments can be adsorbed, and 24.5% of the lipolytic enzyme is adsorbed, indicating that the fifth embodiment has a higher adsorption capacity for the uremic toxin precursor. Intestinal enzymes have a lower adsorption capacity.

Further experimental results show that the adsorbent contains polyacrylonitrile activated carbon fibers having the following characteristics: (1) an average diameter of 5-30 μm, (2) a BET specific surface area of 390 m ² /g or more, and (3) a total acidic group of more than 1.2. The meq/g or total basic base is greater than 1 meq/g, that is, the high adsorption capacity to the uremic toxin precursor, and the low adsorption capacity to the intestinal enzyme protein, so that it can interfere with the normal operation of the gastrointestinal tract. Slows the rate of progression of renal function and reduces the incidence of dialysis treatment. Among them, when the average diameter of the activated carbon fiber is 5 to 10 μm , the adsorbent has an excellent effect of reducing urinary toxin in the body. When the average length of the activated carbon fibers is 20 μm or more, the adsorbent has an excellent effect of lowering urinary toxins in the body. When the BET specific surface area of the activated carbon fiber is 900 to 1500 m ² /g, the adsorbent has an excellent effect of lowering urinary toxin in the body. When the total acidic group of the activated carbon fiber is more than 1.2 to 1.7 meq/g or the total basic group is more than 1 to 1.7 meq/g, the adsorbent has an excellent effect of reducing urinary toxin in the body. When the total acidic group of the activated carbon fiber is 1.253~1.7 meq/g or the total basic group is 1.26~1.685 meq/g, the adsorbent has better effect of reducing urinary toxin in the body.

Further experiments have found that the adsorbent provided by the present invention comprises polyacrylonitrile activated carbon fiber which can be oxidized by Zoltek Companies, Inc., polyacrylonitrile carbon fiber cloth (Panex ^® 30,) in an aqueous carbon dioxide gas at 700. It can be formed by grinding at ~1000 °C for 1~60 minutes, or by other brands (with or without barium or asphalt) of polyacrylonitrile carbon fiber under the same conditions.

After further experiments, it was found that the surface of the polyacrylonitrile activated carbon fiber was attached. The active particles of silver, gold, aluminum, lead, zinc, copper or titanium dioxide will enhance the ability of the adsorbent of the present invention to reduce intestinal bacteria, thereby reducing the concentration of sulphate-derived phenol in rat serum. Among them, the effect of the active particles is preferably from 1 nm to 500 μm.

The above is only the description of the different preferred embodiments of the present invention, and is not intended to limit the present invention. The scope of the implementation of the Ming Dynasty, the simple changes made without the spirit of this creation, should still fall within the scope of the invention intended to be protected.

10‧‧‧Polyacrylonitrile activated carbon fiber

Claims (10)

An adsorbent capable of reducing urinary toxins in the body, comprising: polyacrylonitrile activated carbon fiber having the following characteristics: (1) an average diameter of 5 to 30 μm ; (2) a BET specific surface area of 390 m ² /g or more; The total acidic group is greater than 1.2 meq/g or the total basic group is greater than 1 meq/g. According to claim 1, the adsorbent for reducing urinary toxin in the body, wherein the polyacrylonitrile activated carbon fiber has a total acid group of more than 1.2 meq/g to 1.7 meq/g or a total basic group of more than 1 meq/g to 1.7 meq/ g. According to claim 1, the adsorbent for reducing urinary toxin in the body, wherein the polyacrylonitrile activated carbon fiber has a total acid group of 1.253 meq/g to 1.7 meq/g or a total basic group of 1.26 meq/g to 1.685 meq/g. . The adsorbent for reducing urinary toxins in the body according to claim 1, wherein the polyacrylonitrile activated carbon fibers have an average length of 20 μm or more. The adsorbent for reducing urinary toxin in the body according to claim 1, wherein the polyacrylonitrile activated carbon fiber is formed by oxidizing polyacrylonitrile carbon fiber in an aqueous carbon dioxide gas at 700 to 1000 ° C for 1 to 60 minutes. According to claim 1, the adsorbent for reducing urinary toxin in the body, wherein the polyacrylonitrile activated carbon fiber is formed by oxidation of a polyacrylonitrile carbon fiber cloth in an aqueous carbon dioxide gas at 700 to 1000 ° C for 1 to 60 minutes. The polyacrylonitrile carbon fiber is composed of 90% by weight of polyacrylonitrile plus 10% by weight of Rayon or petroleum pitch. According to claim 1, the adsorbent for reducing urinary toxin in the body, wherein the polyacrylonitrile activated carbon fiber has an average diameter of 5 to 10 μm . The adsorbent for reducing urinary toxin in the body according to claim 1, wherein the polyacrylonitrile activated carbon fiber has a BET specific surface area of from 900 to 1,500 m ² /g. The adsorbent for reducing urotoxin in the body according to claim 1 further comprises a plurality of active particles attached to the surface of the polyacrylonitrile activated carbon fiber, wherein the active particles are composed of silver, gold, aluminum, lead, zinc, copper or titanium dioxide. The adsorbent for reducing urinary toxins in the body according to claim 9, wherein the active particles have a particle diameter of from 1 nm to 500 μm .