A solid phase preparation method for colloidal bismuth pectin

Abstract

The present invention discloses a solid phase preparation method of colloidal bismuth pectin, which uniformly mixes pectin, bismuth reagent and alkaline reagent to obtain a mixture, the mixture is placed in a stainless steel ball milling tank and stainless steel ball milling beads are added, and the mixture is put into a ball mill for ball milling, and then the ground material powder after ball milling is refined, that is, the ground material powder is added to deionized water, heated, stirred and washed, centrifuged, and the lower layer of precipitation is removed, and the pectin bismuth is obtained after vacuum drying under reduced pressure. The mechanochemically prepared bismuth pectin is characterized by FT-IR, XRD, TGA and XPS, and the aggregation phenomenon of bismuth pectin in an acidic environment is studied by SEM and rheology. The structural characteristics and gelling effect of the prepared bismuth pectin are consistent with those of commercially available bismuth pectin. Therefore, the method for preparing bismuth pectin by the method of the present invention can not only reduce the reaction steps, but also reduce the use of a large amount of solvents, save time, and reduce the three wastes. It is a green, friendly and industrialized process route.

Description

Technical Field

[0001] The invention relates to the technical field of drug preparation, in particular to a method for directly preparing colloidal bismuth pectin in a solid phase by applying a mechanochemical technique. Background Art

[0002] The pathogenesis of gastric ulcer is relatively complex, mainly due to the imbalance of the physiological environment in the stomach and the weakening or destruction of the defensive mucosal barrier. Studies have shown that Helicobacter pylori (Hp) in the stomach is closely related to gastric ulcer. Therefore, various treatment options have been proposed to eradicate Hp, among which proton pump inhibitors (PPI) combined with antibiotics are commonly used to treat Hp infection. However, due to the increase in antibiotic resistance, its effectiveness has decreased. But bismuth compounds can ignore the antibiotic resistance of Hp and improve the eradication efficiency. Therefore, it is recommended to use bismuth-containing treatment options to completely eradicate Hp, with a cure rate of up to 93.7%.

[0003] Bismuth pectin is an indeterminate complex composed of pectin and bismuth. The large number of carboxyl groups in pectin gives it a strong affinity for bismuth. Compared with traditional bismuth compounds, the biocompatibility and biodegradability of pectin make bismuth pectin safer. In addition, the gel properties of pectin may provide better protection for ulcers in the gastric environment, because pectin, as a ligand for bismuth ions, can not only enhance the colloidal properties of bismuth pectin, allowing it to form a sol with higher viscosity in acidic media, but also has a stronger affinity with the ulcer surface, forming a stronger protective film on the surface of the gastric mucosa to protect the gastrointestinal tract. Therefore, bismuth pectin is usually used in combination with other drugs in clinical practice to treat gastrointestinal diseases caused by Helicobacter pylori. It is one of the most commonly used drugs for the adjuvant treatment of gastric ulcers and has broad market prospects and application development value.

[0004] At present, the method for preparing bismuth pectin at home and abroad is mainly the solution method (such as CN105461823a, CN1088437a): This method can be summarized into the following steps. First, a large amount of strong alkali (usually sodium hydroxide and potassium hydroxide) and complexes such as sorbitol are used to dissolve bismuth salts such as bismuth nitrate to obtain a bismuth alkali solution, and then the bismuth alkali solution is added to the swollen pectin aqueous solution to react, and a large amount of ethanol is used for alcohol precipitation and repeated washing, drying and crushing to obtain colloidal bismuth pectin. As the most important production method of colloidal bismuth pectin, this method has more prominent problems. (1) Since various bismuth salts are water-insoluble compounds, a large amount of high-concentration strong alkali solution (usually up to 40% w / w or more) is required to form a soluble salt. The use of strong alkali will produce a large amount of alkaline waste liquid and bismuth-containing wastewater, and the environmental protection problem is prominent. (2) The preparation of bismuth base also requires the addition of complexing agents such as sorbitol to increase solubility. These substances will be adsorbed into the product and affect the purity of the colloidal bismuth pectin. It is reported that excessive oral administration of sorbitol can cause diarrhea and digestive disorders. Therefore, although sorbitol can be used appropriately as a food additive, its content needs to be controlled as much as possible. In addition, it will undergo the Maillard reaction under strong alkaline conditions, causing the product color to darken and the quality to deteriorate. (3) The separation and purification process of bismuth pectin requires the use of a large amount of ethanol, and the problems of product solvent residue and solvent contamination should not be ignored.

[0005] In response to the above problems, Chinese patent CN202010214929.X reported an improved solution, which is to add bismuth nitrate to sorbitol aqueous solution to dissolve it, adjust the pH value of the solution to 7-8 with potassium hydroxide solution, stand and separate the precipitate, and wash it with water to obtain a paste-like bismuth base precipitate; add pectin slurry to the bismuth base precipitate, and then add potassium hydroxide solution to react with salt to prepare colloidal pectin bismuth, first add potassium hydroxide-ethanol solution and centrifuge to remove water, then add ethanol to stir and wash, centrifuge to remove the solution, and dry to obtain the colloidal pectin bismuth finished product. This invention patent uses bismuth base precipitate to react with pectin slurry, which solves the problem of excessive retention of co-solvent sorbitol as an added impurity in the colloidal pectin bismuth finished product. The prepared colloidal pectin bismuth finished product has a sorbitol content of less than 3.5% and a free bismuth content of less than 0.8%. Although the possible problems of sorbitol have been solved, the problems of ethanol use and strong alkali waste liquid are still prominent. Summary of the invention

[0006] In view of the above technical problems existing in the prior art, the purpose of the present invention is to provide a solid phase preparation method of bismuth pectin which is environmentally friendly, simple to operate, safe and reliable in production, has a short cycle, low cost, high product yield and good purity.

[0007] The design idea of ​​the present invention is to use mechanochemical reaction to realize green preparation of bismuth base and bismuth pectin under solid phase conditions, eliminate the use of solvent sorbitol and ethanol solvent, and reduce the generation of alkaline waste liquid. Under the action of mechanical force, bismuth salt directly reacts with strong base and pectin in solid phase to obtain bismuth pectin, and bismuth pectin can be obtained by washing with a small amount of water.

[0008] The technical solution adopted by the present invention is as follows:

[0009] A solid phase preparation method of colloidal bismuth pectin is carried out according to the following steps: pectin, a bismuth reagent and an alkali reagent are uniformly mixed to obtain a mixture, the mixture is placed in a stainless steel ball milling tank and stainless steel ball milling beads are added, the mixture is placed in a ball mill for ball milling, and then the ground powder after ball milling is refined, that is, the ground powder is added to deionized water, heated, stirred and washed, centrifuged, a lower layer of precipitation is taken, and the pectin bismuth is obtained after reduced pressure and vacuum drying.

[0010] Furthermore, the bismuth reagent is one of the following: bismuth hydroxide, bismuth nitrate, preferably bismuth nitrate; the alkaline reagent is one of the following: sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, preferably potassium hydroxide.

[0011] Furthermore, the mass ratio of the bismuth reagent to pectin is 10:1 to 1:10, and the mass ratio of the alkaline reagent to pectin is 10:1 to 1:10.

[0012] Furthermore, the mass ratio of the bismuth reagent to pectin is 1:1, and the mass ratio of the alkaline reagent to pectin is 4:1.

[0013] Furthermore, the ball mill is a vibrating ball mill, the diameter of the stainless steel ball milling beads is 15-30 mm, and the material-to-ball ratio of the ball mill is 1:5-30, preferably 1:10.

[0014] Furthermore, the ball milling frequency is 5 to 30 Hz, preferably 25 Hz; the ball milling time is 5 to 30 min, preferably 10 min.

[0015] Furthermore, in the process of refining the ground material powder, the amount of deionized water added is 6-20 g / g based on the total mass of the ground material, the stirring and washing temperature is 50-70° C., and the washing time is 5-20 min.

[0016] The present invention utilizes mechanochemical reaction, which can overcome important factors affecting the reaction such as the solubility of solid substances, and is conducive to solving the problems of excessive alkaline waste liquid, safety in the use of sorbitol, and pollution from a large amount of organic waste liquid in the current production of bismuth pectin. It realizes green preparation of bismuth pectin while avoiding purity reduction and oral safety problems caused by the use of sorbitol. It is a major breakthrough in the traditional preparation method of bismuth pectin and is of great significance.

[0017] Compared with the prior art, the present invention has the following beneficial effects:

[0018] (1) No sorbitol needs to be added during the preparation process, and no ethanol needs to be used for impurity removal. There is no organic waste liquid and solvent residue, which is environmentally friendly.

[0019] (2) Under the action of mechanochemistry, a solid phase reaction between bismuth salt, pectin and alkaline reagent is achieved to directly prepare colloidal bismuth pectin, shorten the preparation process and improve the preparation efficiency.

[0020] (3) Compared with the traditional extraction process, the amount of alkaline waste liquid and bismuth-containing wastewater generated is greatly reduced, the process is greener and the cost is lower.

[0021] (4) Compared with the bismuth pectin prepared by the traditional process, the bismuth pectin prepared by the process of the present invention can be better dissociated at the pH of gastric acid, and the released bismuth ion gel has a better stomach protection effect and has better stability at pH values ​​of 2.2 and 1.5, that is, it can effectively protect the gastrointestinal mucosa.

[0022] In summary, the present invention has the advantages of being environmentally friendly, simple in process, low in harmful substance usage, short in production cycle, and simple in operation. The physical properties and rheological characteristics of the prepared colloidal pectin bismuth are superior to those of commercially available products. The present invention is a better method for preparing pectin bismuth with industrial promotion prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 The XRD diagrams of the bismuth gum prepared in Examples 1-12 and commercially available bismuth gum are compared;

[0024] Figure 2 1 is the XRD diagram of bismuth pectin prepared under different ball milling times and ball milling frequencies of the present invention;

[0025] Figure 3A FI-IR spectra of bismuth pectin prepared in Examples 1, 6 and 11 of the present invention, bismuth pectin available on the market and pectin;

[0026] Figure 3B The DTG curves of the products of Example 1, Example 6, and Example 11 of the present invention, the pectin raw material, and the commercially available bismuth pectin;

[0027] Figure 3C The products of Example 1, Example 6, and Example 11 of the present invention, and C of commercially available bismuth gum 1s XPS images;

[0028] Figure 3D The products of Example 1, Example 6, and Example 11 of the present invention, and commercially available bismuth gum 1s XPS images;

[0029] Figure 4 The results are a comparison of the swelling changes of bismuth pectin acid in acidic solutions of the bismuth pectin products of Examples 1, 11, and 6 of the present invention and commercially available bismuth pectin under the same concentration (w / v) conditions;

[0030] Figure 5A This is a graph of the rheological properties of bismuth pectin prepared in Example 11 of the present invention.

[0031] Figure 5B This is the rheological properties diagram of commercially available bismuth pectin. DETAILED DESCRIPTION

[0032] The technical solution of the present invention is described below with specific implementations, but the protection scope of the present invention is not limited thereto. The pectin used in the examples is commercially available pectin derived from citrus.

[0033] Example 1: Physical mixture preparation

[0034] Pectin, bismuth nitrate and potassium hydroxide were respectively ball-milled at 25 Hz for 30 minutes in a ball mill, and 0.50 g of the ball-milled pectin, 0.50 g of the ball-milled bismuth nitrate and 0.30 g of the ball-milled potassium hydroxide were respectively taken, mixed evenly and ground evenly in a mortar as a control physical mixture.

[0035] Embodiment 2:

[0036] Weigh 0.50 g of pectin into a 50 mL stainless steel ball mill, add 0.50 g of bismuth hydroxide, 0.25 g of potassium hydroxide, and then add stainless steel ball mill beads with a diameter of 20 mm (the total mass of the stainless steel ball mill beads is 12.5 g, that is, the material ball milling is 1:10), mix well, put the ball mill into a vibrating ball mill at 25 Hz for 30 minutes, put the powder after the ball milling into a beaker, add 12.5 g of water, heat and stir at 60 ° C for 10 minutes, then use a centrifuge to centrifuge for 5 minutes at 8000 rpm, remove the supernatant, obtain the precipitate, and then freeze-dry to obtain the product.

[0037] Embodiment 3:

[0038] Weigh 0.50 g of pectin into a 50 mL stainless steel ball mill, add 0.50 g of bismuth nitrate, 0.25 g of potassium hydroxide, and then add stainless steel ball mill beads with a diameter of 20 mm (the material ball milling ratio is 1:10). After mixing evenly, put the ball mill into a vibrating ball mill at 25 Hz for 30 minutes. After the ball milling, put the powder into a beaker, add 12.5 g of water, heat and stir at 60°C for 10 minutes, then use a centrifuge at 8000 rpm for 5 minutes, remove the supernatant, obtain the precipitate, and then freeze-dry to obtain the product.

[0039] Embodiment 4:

[0040] Weigh 0.50 g of pectin into a 50 mL stainless steel ball mill, add 0.50 g of bismuth nitrate, 0.25 g of sodium hydroxide, and then add stainless steel ball mill beads with a diameter of 20 mm (the material ball milling ratio is 1:10). After mixing evenly, put the ball mill into a vibrating ball mill at 25 Hz for 30 minutes. After the ball milling, put the powder into a beaker, add 12.5 g of water, heat and stir at 60°C for 10 minutes, then use a centrifuge at 8000 rpm for 5 minutes, remove the supernatant, obtain the precipitate, and then freeze-dry to obtain the product.

[0041] Embodiment 5:

[0042] Weigh 0.50 g of pectin into a 50 mL stainless steel ball mill, add 0.50 g of bismuth nitrate, 0.25 g of sodium carbonate, and then add stainless steel ball mill beads with a diameter of 20 mm (the material ball milling ratio is 1:10). After mixing evenly, put the ball mill into a vibrating ball mill at 25 Hz for 30 minutes. After the ball milling, put the powder into a beaker, add 12.5 g of water, heat and stir at 60 ° C for 10 minutes, and then use a centrifuge to centrifuge for 5 minutes at 8000 rpm, remove the supernatant, obtain the precipitate, and then freeze-dry to obtain the product.

[0043] Embodiment 6:

[0044] Weigh 0.50g of pectin into a 50mL stainless steel ball mill, add 0.50g of bismuth nitrate, 0.25g of calcium carbonate, and then add stainless steel ball mill beads with a diameter of 20mm (the material ball milling ratio is 1:10), mix well, put the ball mill into a vibrating ball mill at 25Hz for 30 minutes, after the ball milling, put the powder into a beaker, add 12.5g of water, heat and stir at 60℃ for 10min, then use a centrifuge to centrifuge for 5min, remove the supernatant, obtain the precipitate, and then freeze-dry to obtain the product.

[0045] Embodiment 7:

[0046] Weigh 0.50 g of pectin into a 50 mL stainless steel ball mill, add 0.50 g of bismuth nitrate, 0.25 g of potassium carbonate, and then add stainless steel ball mill beads with a diameter of 20 mm (the material ball milling ratio is 1:10). After mixing evenly, put the ball mill into a vibrating ball mill at 25 Hz for 30 minutes. After the ball milling, put the powder into a beaker, add 12.5 g of water, heat and stir at 60 ° C for 10 minutes, and then use a centrifuge to centrifuge for 5 minutes at 8000 rpm, remove the supernatant, obtain the precipitate, and then freeze-dry to obtain the product.

[0047] Embodiment 8:

[0048] Weigh 0.50 g of pectin into a 50 mL stainless steel ball mill, add 0.50 g of bismuth nitrate, 0.10 g of potassium hydroxide, and then add stainless steel ball mill beads with a diameter of 20 mm (the material ball milling ratio is 1:10). After mixing evenly, put the ball mill into a vibrating ball mill at 25 Hz for 30 minutes. After the ball milling, put the powder into a beaker, add 12.5 g of water, heat and stir at 60°C for 10 minutes, then use a centrifuge at 8000 rpm for 5 minutes, remove the supernatant, obtain the precipitate, and then freeze-dry to obtain the product.

[0049] Embodiment 9:

[0050] Weigh 0.50 g of pectin into a 50 mL stainless steel ball mill, add 0.50 g of bismuth nitrate, 0.15 g of potassium hydroxide, and then add stainless steel ball mill beads with a diameter of 20 mm (the material ball milling ratio is 1:10). After mixing evenly, put the ball mill into a vibrating ball mill at 25 Hz for 30 minutes. After the ball milling, put the powder into a beaker, add 12.5 g of water, heat and stir at 60°C for 10 minutes, then use a centrifuge at 8000 rpm for 5 minutes, remove the supernatant, obtain the precipitate, and then freeze-dry to obtain the product.

[0051] Embodiment 10:

[0052] Weigh 0.50 g of pectin into a 50 mL stainless steel ball mill, add 0.50 g of bismuth nitrate, 0.20 g of potassium hydroxide, and then add stainless steel ball mill beads with a diameter of 20 mm (the material ball milling ratio is 1:10). After mixing evenly, put the ball mill into a vibrating ball mill at 25 Hz for 30 minutes. After the ball milling, put the powder into a beaker, add 12.5 g of water, heat and stir at 60°C for 10 minutes, then use a centrifuge at 8000 rpm for 5 minutes, remove the supernatant, obtain the precipitate, and then freeze-dry to obtain the product.

[0053] Embodiment 11:

[0054] Weigh 0.50 g of pectin into a 50 mL stainless steel ball mill, add 0.50 g of bismuth nitrate, 0.30 g of potassium hydroxide, and then add stainless steel ball mill beads with a diameter of 20 mm (the material ball milling ratio is 1:10). After mixing evenly, put the ball mill into a vibrating ball mill at 25 Hz for 30 minutes. After the ball milling, put the powder into a beaker, add 12.5 g of water, heat and stir at 60 ° C for 10 minutes, and then use a centrifuge to centrifuge for 5 minutes at 8000 rpm, remove the supernatant, obtain the precipitate, and then freeze-dry to obtain the product.

[0055] Embodiment 12:

[0056] Weigh 0.50 g of pectin into a 50 mL stainless steel ball mill, add 0.50 g of bismuth nitrate, 0.35 g of potassium hydroxide, and then add stainless steel ball mill beads with a diameter of 20 mm (the material ball milling ratio is 1:10). After mixing evenly, put the ball mill into a vibrating ball mill at 25 Hz for 30 minutes. After the ball milling, put the powder into a beaker, add 12.5 g of water, heat and stir at 60°C for 10 minutes, then use a centrifuge at 8000 rpm for 5 minutes, remove the supernatant, obtain the precipitate, and then freeze-dry to obtain the product.

[0057] The XRD diagram comparison results of the bismuth gum prepared in Examples 1-12 and the commercially available bismuth gum are shown in Figure 1 .

[0058] Determination method of bismuth content and free bismuth content in pectin

[0059] The method for determining the content of bismuth in the embodiment of the present invention is as follows: accurately weigh an appropriate amount of the sample to be tested (equivalent to approximately 75 mg of bismuth), add 5 ml of nitric acid solution (2 mol / L) and heat to dissolve, then add 150 ml of water and 2 drops of dimethyl phenol orange indicator solution, and titrate with disodium ethylenediaminetetraacetic acid titration solution (0.05 mol / l) until the solution turns yellow. Record the volume (ml) of disodium ethylenediaminetetraacetic acid titration solution consumed, and each 1 ml of disodium ethylenediaminetetraacetic acid titration solution (0.05 mol / l) is equivalent to 10.45 mg of bismuth. The bismuth content of the sample to be tested is calculated based on the consumption of disodium ethylenediaminetetraacetic acid, and each sample is measured 3 times to obtain the bismuth content of the product of each embodiment.

[0060] The method for determining the content of free bismuth in the embodiment is as follows: take about 1.0 g of the product, accurately weigh it, place it in a 250 mL conical flask, add pH 1.2 100mL of hydrochloric acid solution was shaken and stirred at room temperature for 2h. The supernatant was taken and filtered through a 0.8μm water filter. 10mL of the filtrate was accurately measured and placed in a suitable evaporating dish. It was evaporated to dryness in a water bath. 5mL of nitric acid was added to digest it. It was concentrated and evaporated to dryness. It was allowed to cool to room temperature. 2% nitric acid solution was added to transfer the residue to a 20mL volumetric flask, and the volume was adjusted to the mark. Shake well to prepare the test solution (Note: There are differences between samples from different sources and batches. The concentration was adjusted within the linear range according to the free bismuth content of the sample); a blank solution was prepared in the same way; 1.0mL, 1.5mL, 2.0mL, 2.5mL and 3.0mL of bismuth single element standard solution (1000μg / mL) were accurately measured and placed in 100mL volumetric flasks respectively. The solution was diluted to the mark with 2% nitric acid solution and shake well to prepare a series of standard solutions. Take the standard solution and the test solution, and measure at a wavelength of 223.1 nm according to the atomic absorption spectrophotometry method (General Rule 0406 Method 1) of the 2020 edition of the Chinese Pharmacopoeia, draw a standard curve, calculate the regression equation, and calculate the free bismuth content (the result is in bismuth) according to the regression equation. Repeat the measurement 3 times for each sample. The contents of pectin bismuth and free bismuth in each example are shown in Table 1 below.

[0061] Table 1: Contents of bismuth pectin and free bismuth in various examples

[0062] Example Total pectin bismuth content wt% Free bismuth content ppm 1 19.33 2568.93 2 20.90 660.84 3 18.20 125.21 4 15.24 325.20 5 13.33 1725.63 6 7.41 2678.27 7 15.24 784.22 8 20.92 825.38 9 20.24 472.72 10 19.40 125.80 11 18.11 117.25 12 17.44 676.11 Commercially available bismuth pectin 16.25 110.26

[0063] The results show that the bismuth content of the pectin bismuth prepared in Example 11 is close to that of the commercially available products, which preliminarily indicates that the pectin bismuth is well formed.

[0064] Example 13: Identification of Bismuth Pectin

[0065] The crystal structure of bismuth pectin was determined by X-ray diffractometer (XRD), and the formation of bismuth pectin was confirmed by comparison with commercially available bismuth pectin samples. Method: Using German Bruker D2 phase X-ray diffractometer under the conditions of acceleration voltage of 30 kV, current of 10 mA, and scanning range of 3-60° (2θ), the XRD comparison results of bismuth pectin products prepared in Examples 1-12 are shown in Figure 1 The XRD experiment shows that the pectin bismuth prepared in Example 11 using pectin, potassium hydroxide and bismuth nitrate as raw materials is basically consistent with the XRD peak shape of commercially available pectin bismuth, while the other examples all have free bismuth nitrate absorption peaks. The results show that the pectin bismuth prepared in Example 11 is closest to the commercially available pectin bismuth.

[0066] Embodiment 14:

[0067] The effect of ball milling frequency on the formation of bismuth pectin is as follows: 0.50 g of pectin is weighed into a 50 mL stainless steel ball mill, 0.50 g of bismuth nitrate, 0.30 g of potassium hydroxide, and then a stainless steel ball milling bead with a diameter of 20 mm (the material ball milling ratio is 1:10) is added. After mixing evenly, the ball mill is placed in a vibrating ball mill and ball milled for 30 min at 10 Hz, 15 Hz, 20 Hz, 25 Hz, and 30 Hz. After the ball milling, the powder is placed in a beaker, 12.5 g of water is added, heated and stirred at 60 ° C for 10 min, and then centrifuged at 8000 rpm for 5 min, the supernatant is removed, a precipitate is obtained, and then freeze-dried to obtain a product, and XRD is used to identify whether the product is bismuth pectin.

[0068] The XRD comparison results of the pectin bismuth products prepared at different ball milling frequencies in Example 14 of the present invention are shown in Figure 2 As shown in the figure, the crystal structure of bismuth pectin is most stable at 25 Hz, and its characteristic diffraction peak is most obvious. Therefore, 25 Hz is selected as the optimal ball milling intensity, at which time the semi-crystalline structure of bismuth pectin is more stable.

[0069] Embodiment 15:

[0070] Effect of ball milling time on the formation of bismuth pectin: specifically, 0.50 g of pectin was weighed into a 50 mL stainless steel ball mill, 0.50 g of bismuth nitrate, 0.30 g of potassium hydroxide, and then a stainless steel ball milling bead with a diameter of 20 mm (the material ball milling ratio is 1:10) was added, and after mixing evenly, the ball mill was placed in a vibrating ball mill and ball milled at 25 Hz for 5 min, 10 min, 15 min, 30 min, 45 min, and 60 min. After the ball milling, the powder was placed in a beaker, water was added, heated and stirred at 60 ° C for 10 min, and then centrifuged at 8000 rpm for 5 min, the supernatant was removed, a precipitate was obtained, and then freeze-dried to obtain a product, and XRD was used to identify whether the product was bismuth pectin.

[0071] The XRD comparison results of the pectin bismuth products prepared at different ball milling times in Example 15 of the present invention are shown in Figure 2 As shown in the figure, with the increase of ball milling time, the height of the pectin bismuth diffraction peak also increases. However, when the ball milling time is greater than 30 minutes, a prominent small diffraction peak appears in the XRD diagram of the pectin bismuth. This may be because as the ball milling time increases, the mechanical energy also increases, which destroys the structure of the pectin bismuth. Therefore, the optimal ball milling time is selected as 30 minutes.

[0072] Example 16: Preparation and Characterization of Bismuth Pectin

[0073] Characterization of the characteristic groups of bismuth pectin by Fourier transform infrared spectroscopy (FI-IR): 0.25 mg of dried sample was mixed with 250 mg of potassium bromide, pressed into a thin sheet, and then placed in the sample chamber. A Fourier spectrophotometer was used at 4000-400 cm -1 The measurement was performed within the range, with each spectrum scanned 32 times and a resolution of 4 cm -1 The FI-IR spectra of the product of Example 1, the product of Example 11, the product of Example 6, the pectin raw material and the commercially available bismuth pectin are as follows: Figure 3A As shown, the infrared spectrum of the product of Example 11 is 2941 cm -1 The characteristic absorption peak signal at 1749cm -1 The characteristic absorption peak at 1416cm -1 A new characteristic absorption peak and an absorption peak at 1646 cm -1 To 1604cm -1 The blue shift may be due to the stretching vibration of the carbonyl anion. The infrared spectrum of the product of Example 11 is at 571 cm -1 A new characteristic peak appears at , which may correspond to the symmetric stretching vibration of the Bi-O bond. The IR spectrum is close to that of commercially available bismuth pectin.

[0074] Characterization of thermal stability of bismuth pectin by thermogravimetric analysis: The thermal stability was measured using a TGA STA449F3 instrument. About 5 mg of the sample was placed in an uncovered alumina crucible and measured under the conditions of a nitrogen flow rate of 20 mL / min, a heating range of 30 to 600°C, and a heating rate of 10°C / min. The DTG curves of the products of Examples 1, 6, and 11 of the present invention, the pectin raw material, and the commercially available bismuth pectin are shown in FIG. Figure 3B As shown in the figure, it can be obtained that the bound water endothermic peak in the DTG curve of Example 11 moves from 73.1°C to 58.6°C, while the decomposition endothermic peak of pectin moves from 251.1°C to 241.1°C, which is significantly different from that of Example 6 and Example 1 (physical mixture), but is basically consistent with the commercially available bismuth pectin, indicating the formation of bismuth pectin.

[0075] X-ray photoelectron spectroscopy (XPS) was used to characterize the binding of bismuth ions: Al-Kα radiation was used as the excitation source, and the X-ray photoelectron spectrum was measured on the ESCA. 1s The peak (284.6 eV) is used to calibrate all binding energies. 1s XPS pictures Figure 3C , and O 1s XPS pictures Figure 3D As can be seen from the figure, both the product of Example 11 and the commercially available bismuth pectin can be 1sA new peak was observed in the XPS graph at 533.30 eV, corresponding to Bi-O, and due to Bi 3+ With COO - Complexation, resulting in C 1s and O 1s The binding energy of O=CO in the XPS spectrum shifts to high energy, indicating the O=CO-Bi structure corresponding to bismuth pectin, and the formation of bismuth pectin. The above characterization experiments all show that this method successfully uses mechanochemistry to prepare bismuth pectin.

[0076] Example 18: Aggregation and rheological properties of pectin bismuth acid solution

[0077] 0.05 g of bismuth pectin powder was placed in a 20 mL sample bottle and dispersed with 10 mL of pure water. The pH value of the solution was adjusted to 6.8, 4.6, 3.1, 2.2, 1.5 and 0.8 with 0.1 mol / L hydrochloric acid. After storage at 25°C for 12 hours, the state of the bismuth pectin suspension was observed. The product of Example 6 and the physical mixture were used as the control group. Figure 4 As shown, Figure 4 The products of Example 1, Example 11, Example 6 and commercially available bismuth pectin aggregated in an acidic solution at the same concentration (w / v). As can be seen from the figure above, Example 1 and Example 6 precipitated at the bottom of the bottle and were easily dissolved under low pH (1.5) conditions because pectin in the above system failed to coordinate with bismuth ions and Bi 3+ It is easily hydrolyzed in aqueous solution (pKa=1.51) to form insoluble bismuth hydroxide rather than colloid. For Example 11 and commercially available bismuth pectin, the precipitation of the two is highly similar in aqueous solution with pH values ​​of 6.8 and 4.6. After the bismuth pectin solution is further restored to pH value 6.8, both can form stable precipitation forms.

[0078] In order to further study the effect of pH on the flow behavior of bismuth pectin, a Mars40 rheometer was used to record the viscosity of bismuth pectin when the flow rate was increased. The shear rate range was 0.01-1000r / s, and the temperature during the measurement was maintained at 25°C. The steady-state flow behavior of bismuth pectin suspensions under different pH conditions was studied to evaluate the interaction between bismuth pectin particles. The rheological properties of bismuth pectin prepared in Example 11 of the present invention and commercially available bismuth pectin are shown in Figures 1 and 2. Figure 5A and Figure 5B As shown, according to Figure 5A and Figure 5B We found that Example 11 and the suspension of bismuth pectin were similar to Newtonian fluids and exhibited high shear rates, which were consistent with the characteristics of commercially available bismuth pectin, indicating that Example 11 can achieve the same gelation effect as commercially available bismuth pectin.

[0079] The contents described in this specification are merely an enumeration of implementation forms of the inventive concept, and the protection scope of the present invention should not be regarded as being limited to the specific forms described in the embodiments.

Claims

1. A solid phase preparation method for colloidal bismuth pectin, characterized in that: Pectin, bismuth reagent and alkali reagent are mixed uniformly to obtain a mixture, the mixture is placed in a stainless steel ball milling jar and stainless steel ball milling beads are added, and the mixture is placed in a ball mill for ball milling. Then, the ground powder after ball milling is refined, that is, the ground powder is added to deionized water, heated, stirred, washed, centrifuged, the lower precipitate is taken, and the pectin bismuth is obtained after reduced pressure and vacuum drying.

2. A solid phase preparation method for colloidal bismuth pectin as claimed in claim 1, characterized in that: The bismuth reagent is one of the following: bismuth hydroxide, bismuth nitrate; the alkaline reagent is one of the following: sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate.

3. A solid phase preparation method for colloidal bismuth pectin as claimed in claim 2, characterized in that: The bismuth reagent is bismuth nitrate; and the alkaline reagent is potassium hydroxide.

4. A solid phase preparation method for colloidal bismuth pectin as claimed in claim 2, characterized in that: The mass ratio of the bismuth reagent to pectin is 10:1-1:10, and the mass ratio of the alkaline reagent to pectin is 10:1-1:

10.

5. A solid phase preparation method for colloidal bismuth pectin as claimed in claim 4, characterized in that: The mass ratio of the bismuth reagent to pectin is 1:1, and the mass ratio of the alkaline reagent to pectin is 4:

1.

6. A solid phase preparation method for colloidal bismuth pectin as claimed in claim 1, characterized in that: The ball mill is a vibrating ball mill, the diameter of the stainless steel ball mill is 15-30mm, and the material-to-ball ratio of the ball mill is 1:5~30.

7. A solid phase preparation method for colloidal bismuth pectin as claimed in claim 6, characterized in that: The material-ball ratio of ball mill is 1:

10.

8. A solid phase preparation method for colloidal bismuth pectin as claimed in claim 1, characterized in that: The ball milling frequency is 5~30Hz, and the ball milling time is 5~30 min.

9. A solid phase preparation method for colloidal bismuth pectin as claimed in claim 8, characterized in that: The ball milling frequency was 25 Hz and the ball milling time was 10 min.

10. The solid phase preparation method of colloidal bismuth pectin according to claim 1, characterized in that: During the refining of the ground material powder, the amount of deionized water added is 6-20 g / g based on the total mass of the ground material, the stirring and washing temperature is 50-70° C., and the washing time is 5-20 min.

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