A rapidly absorbed low-irritation oral electrolyte replacement solid formulation and a method of making the same

Abstract

A kind of fast absorption low irritation oral electrolyte solution solid preparation and preparation method thereof, according to weight fraction, including the following raw materials: sodium chloride 1.8~2.6 parts, potassium chloride 1.1~1.6 parts, potassium malate 0.9~1.3 parts;L-alanine 3.2~4.5 parts;Erythritol 12~18 parts, maltitol 6~10 parts;Hydrogenated palm oil 2.2~3.0 parts;Polydextrose 1.5~2.5 parts;Malic acid 0.4~0.8 parts;Anhydrous glucose 0.675~1.35 parts;Erythritol is made up to 100 parts;Sodium chloride, potassium chloride, potassium malate are mixed uniformly, melt hydrogenated palm oil is sprayed and coated, other raw materials are added and mixed to obtain the product.The advantages are: salt supplementing efficiency is good, gastrointestinal irritation can be avoided, whole formula is low in glycemic, suitable for special population such as diabetic patients, infants, the elderly.

Description

Technical Field

[0001] This invention belongs to the field of medical and functional electrolyte supplements, and relates to a rapidly absorbed, low-irritation oral electrolyte rehydration solid preparation and its preparation method. In particular, it relates to a rapidly rehydration, highly tolerable, rapidly absorbed, low-irritation oral electrolyte rehydration solid preparation and its preparation method suitable for diarrhea dehydration, heatstroke, exercise dehydration, and mild postoperative dehydration. Background Technology

[0002] Oral rehydration salts (ORS) are currently recognized globally as the first-line treatment for correcting dehydration and replenishing electrolytes. Since the World Health Organization promoted the basic formulas of ORS I, ORS II, and ORS III, these preparations have played an irreplaceable role in the treatment of diarrhea-induced dehydration, heatstroke, exercise-induced dehydration, and mild postoperative dehydration. The core absorption-promoting mechanism of these three generations of ORS lies in the sodium-dependent glucose transporter (SGLT-1) on the apical membrane of intestinal epithelial cells, which simultaneously transports sodium ions and glucose molecules. As glucose is actively absorbed, it carries sodium ions into the cells, and the resulting osmotic gradient drives the passive absorption of water from the intestinal lumen into the bloodstream.

[0003] The existing three generations of oral rehydration salts—ORSⅠ, ORSⅡ, and ORSⅢ—all utilize the single glucose SGLT-1 pathway as their absorption core, with osmotic pressure concentrated in the hypotonic range of 220–250 mOsm / kg. For example, ORSⅢ has a glucose concentration of 75 mmol / L and a total osmotic pressure of 245 mOsm / kg; its osmotic pressure is close to that of the intestinal epithelium in the hypotonic range, resulting in gentle absorption. However, due to the hypotonic osmotic pressure, the rate of rehydration for severe dehydration is slow, and the recovery time from dehydration is prolonged. Furthermore, ORSⅢ relies solely on the SGLT-1 channel for sodium ion absorption, resulting in a limited rehydration pathway. When diarrhea damages the small intestinal epithelium and SGLT-1 protein expression decreases, sodium and water absorption efficiency is significantly reduced. The inorganic salts (sodium chloride and potassium chloride) in ORSⅢ formulations exist as free ions after dissolution, directly irritating the gastric mucosa and causing adverse reactions such as nausea and vomiting. The rehydration mechanism depends on high-concentration glucose to drive sodium absorption, which can easily cause intestinal osmotic pressure imbalance, hypernatremia, abdominal distension, and blood sugar spikes. It is suitable for a limited population and is contraindicated for diabetic patients. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to provide a fast-absorbing, low-irritation oral electrolyte rehydration solid preparation and its preparation method, which has good salt replenishment efficiency, avoids gastrointestinal irritation and the risk of blood sugar spikes, and is suitable for a wide range of people.

[0005] The technical solution of this invention is: A rapidly absorbed, low-irritation oral electrolyte rehydration solid dosage form, characterized in that it comprises the following ingredients by weight: Electrolyte complex components: 1.8–2.6 parts sodium chloride, 1.1–1.6 parts potassium chloride, and 0.9–1.3 parts potassium malate; Amino acid synergistic absorption component: L-alanine 3.2–4.5 parts; Polyol matrix: 12-18 parts erythritol, 6-10 parts maltitol; Ion-isolated microcapsule wall material: 2.2–3.0 parts hydrogenated palm oil; Anti-caking stabilizer: 1.5–2.5 parts polydextrose; Acidity regulator: 0.4–0.8 parts malic acid; SGLT1 activator: 0.675–1.35 parts of anhydrous glucose; The remaining amount was made up to 100 parts with erythritol; This composition is free of sodium citrate, sodium bicarbonate, zinc, probiotics, and lactose. It utilizes an organic buffer system composed of malic acid and potassium malate to replace traditional inorganic buffer salts, preventing gas production and gastrointestinal irritation; lactose is omitted to avoid osmotic diarrhea; zinc ions are not added to prevent competition with sodium ions for transport and thus reduce absorption rate; probiotics are omitted to prevent bacterial degradation and consumption of glucose substrates, ensuring precise activation of the SGLT-1 transport channel and improving the stability of the powder during storage. Combined with a dry microencapsulation process, it achieves rapid, low-irritation rehydration.

[0006] Furthermore, the glucose concentration of the rapidly absorbed, low-irritation oral electrolyte rehydration solution solid preparation after reconstitution is controlled at 15–30 mmol / L; the osmotic pressure is 265–280 mOsm / kg.

[0007] A method for preparing a rapidly absorbed, low-irritation oral electrolyte rehydration solid dosage form, the specific preparation steps of which are as follows: (1). Preprocessing All powder raw materials are passed through an 80-100 mesh sieve to remove agglomerated particles; (2). Ion microcapsule coating Sodium chloride, potassium chloride, and potassium malate were mixed evenly and then coated with molten hydrogenated palm oil to obtain acid-resistant ion-isolated microcapsules. (3). Premixed sugar alcohol system Erythritol, maltitol, polydextrose, and anhydrous glucose are mixed in equal increments. The equal increment mixing process means that the amount added in each subsequent batch is equal to the total mass of the current mixture. In other words, the total amount of material doubles after each addition, and the mixture is expanded step by step. The amount of polydextrose added in this invention is relatively small, while the amounts of maltitol and erythritol are larger. The pharmacological reasons are as follows: ① Polydextrose does not participate in the SGLT-1 transport channel activation process and has no active absorption-promoting effect; ② The combination of erythritol (zero calories, rapid absorption and excretion in the small intestine) and maltitol (slow and stable energy supply) will not raise blood sugar and can stably regulate the osmotic pressure of the rehydration solution, precisely matching trace amounts of glucose to stably maintain an SGLT-1 activation concentration of 15-30 mmol / L; ③ If polydextrose is used as the main filler, it will change the osmotic pressure environment of the system, interfere with the glucose-sodium ion cotransport efficiency, cause a decrease in the rehydration rate, and fail to achieve the technical effect of rapid electrolyte correction. The reasons for the stability of the powder production process are as follows: ① Polydextrose has strong hygroscopicity and high powder viscosity. If the ratio is too high, it is easy to absorb moisture, clump, and separate into layers, making it impossible to achieve the sugar alcohol incremental mixing process of this patent; ② Erythritol has extremely low hygroscopicity and is stable in a production environment with humidity ≤35%. It has good crystal flowability. When combined with maltitol, the powder is loose and uniform, which can perfectly adapt to the graded low-speed mixing process and solve the industry defects of uneven powder mixing and easy moisture absorption during storage; ③ The sugar alcohol powder particles are regular and will not break after being mixed with oil microcapsules, which can preserve the complete structure of the microcapsules for a long time.

[0008] (4). Total mixture The acid-resistant ion-isolated microcapsules obtained in step (2), the sugar alcohol system premix obtained in step (3), L-alanine, and malic acid were put into a three-dimensional mixer. Finally, the remaining amount of erythritol in the formula was added to make up the total mass to 100 parts. The mixture was mixed at low speed to obtain a uniform composite powder. (5) Aseptic dispensing The composite powder obtained in step (4) is directly packaged into oral powder, without granulation, tableting, effervescence, or preparation into oral liquid.

[0009] Furthermore, the specific operation sequence of the equal-quantity incremental mixing process described in step (3) is as follows: 1) Add all the polydextrose, anhydrous glucose, and an equal weight of erythritol and maltitol powder, and mix at a low speed of 15 r / min for 5 min. 2) Add the remaining erythritol and maltitol mixed powder equal to the total weight of the current mixed powder, and mix well; continue to double the amount until all the erythritol and maltitol mixed powder except for the replenished amount of erythritol has been added. Each time you mix, the low speed stirring speed is 15r / min and the stirring time is 5min.

[0010] Furthermore, in step (4), the mixing speed of the low-speed stirring is 15 r / min, and the mixing time is 5 to 15 min. The purpose of using low-speed mixing is to reduce the shear force during the stirring process, avoid the thermal degradation of active components and particle breakage, reduce the electrostatic agglomeration of powder and air entrainment, improve the uniformity of powder mixing, and ensure the quality of subsequent formulation.

[0011] Furthermore, in steps (1) to (5), the ambient humidity is ≤35%, and erythritol maintains crystal fluidity under the humidity conditions, working together with maltitol to achieve loose and uniform powder, avoiding moisture absorption and stratification.

[0012] The principle of electrolyte replenishment in this invention: (1) Dual pathway synergistic absorption activation: ① Glucose transporter SGLT-1 (sugar alcohol mediated); ② Sodium amino acid cotransport channel B 0 AT1 (SLC6A19). Significantly improves the absorption rate of sodium and potassium ions in the small intestine, enabling rapid salt replenishment within 30 minutes.

[0013] (2) Microcapsule acid-isolated sustained release: Electrolytes are encapsulated by oil wall material, and are not released in the stomach but released at a specific point in the small intestine, completely eliminating stomach irritation.

[0014] This invention constructs the SGLT-1 glucose-sodium cotransport pathway, with L-alanine cascading to mediate intestinal epithelial B-cell pathways. 0 Type B neutral amino acid transport system (B 0 This novel dual-pathway absorption system utilizes SGLT1 and its downstream basal amino acid transport system. The two transport pathways are independent and do not overlap in their mechanisms of action: The first pathway involves SGLT1-mediated glucose-sodium ion co-absorption; only the minimum effective dose of anhydrous glucose is added, with the glucose concentration controlled at 15-30 mmol / L after reconstitution, specifically activating the SGLT-1 transporter protein in the small intestinal epithelium, where one glucose molecule co-transports two Na⁺ ions. Erythritol, maltitol, and polydextrose are sugar alcohols and cannot activate SGLT1; trace amounts of glucose remaining in the raw materials are merely production impurities and do not reach the effective concentration; only anhydrous glucose is added as the active ingredient in this pathway. The second pathway involves L-alanine progressively mediating the absorption of basal amino acids in the intestinal epithelium. 0 Type B neutral amino acid transport system (B 0 AT1) and its downstream basal-side amino acid transport system are absorbed in synergistic ways; L-alanine in the formula can specifically activate L-alanine to mediate the stepwise absorption of intestinal epithelial B-cells. 0 Type B neutral amino acid transport system (B 0AT1 and its downstream basal-side amino acid transport system. It independently carries sodium ions into intestinal epithelial cells; this process is independent of glucose and not limited by SGLT-1 activity. Two absorption pathways operate in parallel. In cases of diarrhea, if SGLT-1 in the upper small intestine is impaired, L-alanine gradually mediates the absorption of sodium ions into intestinal epithelial basal-side amino acids. 0 Type B neutral amino acid transport system (B 0 AT1 and its downstream basal-side amino acid transport system channels can still efficiently absorb sodium ions; when SGLT-1 activity in the lower intestinal tract is sufficient, both pathways function simultaneously, resulting in a faster fluid resuscitation rate than the traditional ORSⅢ single pathway. Its beneficial effects are: (1) This invention mediates the intestinal epithelial B-cell pathway stepwise through SGLT-1 and L-alanine. 0 Type B neutral amino acid transport system (B 0 AT1 and its downstream basal-side amino acid transport system. Dual-channel parallel absorption allows normal serum ion levels to be reached within 25–30 minutes, increasing salt replenishment rate by over 50%.

[0015] (2) This invention constructs a stepwise mediated intestinal epithelial B-cell reaction between SGLT-1 and L-alanine. 0 Type B neutral amino acid transport system (B 0 AT1) and its downstream basal-side amino acid transport system. A dual-channel synergistic absorption mechanism allows sodium ions to rapidly bind with glucose or L-alanine after entering the gastrointestinal tract, forming molecular complexes. This reduces the prolonged attachment of free ions to the gastric wall surface, significantly decreasing direct ion stimulation of the gastric mucosa. Simultaneously, the formulation's osmotic pressure is controlled at 265–280 mOsm / kg, close to the osmotic pressure of human blood plasma, preventing discomfort caused by excessively high osmotic pressure. Hydrogenated palm oil forms a thin protective film on the gastric mucosa, further isolating the stomach wall from the stimulation of small amounts of uncomplexed ions, significantly reducing gastric stress response and improving tolerance in infants and individuals with sensitive gastrointestinal tracts.

[0016] - (3) The anhydrous glucose concentration of this invention is controlled at 15-30 mmol / L, which is only 20%-40% of the glucose concentration of third-generation oral rehydration salts (ORS-III). The glucose concentration of traditional ORS-III is about 75 mmol / L. High concentrations of glucose can easily cause high intestinal osmotic pressure and significant blood sugar rise. This formula uses only a low dose of glucose to precisely activate the SGLT-1 transporter, achieving rapid sodium replenishment while significantly reducing osmotic pressure and blood sugar load. Combined with the low blood sugar characteristics of erythritol (which hardly enters the blood circulation, hardly raises blood sugar, and does not stimulate insulin secretion), maltitol (which is slowly digested and absorbed, has a much lower glycemic index than glucose, and has small blood sugar fluctuations), and polydextrose (a water-soluble dietary fiber that is basically not absorbed by the small intestine, ferments slowly only in the colon, and has minimal impact on blood sugar), the overall blood sugar load is extremely low. The sugar alcohol compound system significantly reduces the amount of glucose used, overcoming the defects of conventional ORS-III, which has a high glucose content and cannot be taken by diabetic patients. It can be safely taken by people with impaired glucose tolerance, mild hyperglycemia, and diabetic patients during diarrhea and dehydration.

[0017] (4) Potassium malate combined with malic acid stabilizes the intestinal pH, further improves the intestinal environment, and enhances the activity of dual-pathway transport proteins; hydrogenated palm oil has a protective effect on the intestinal mucosa.

[0018] (5) The polyol system has good moisture-proof and anti-caking properties. Combined with the exclusive low-speed mixing process, it solves the problems of large density difference between inorganic salt crystals and fluffy sugar alcohol powder, particle breakage during high-speed mixing, glucose degradation due to heat, and poor powder mixing uniformity. The shelf life at room temperature can reach more than 24 months. There is no risk of impurity increase or raw material degradation during long-term storage.

[0019] In summary, this invention utilizes a dual substrate of polyols and amino acids, employing dual transport channels, tolerating moderately high osmotic pressure, and significantly improving ion transport efficiency for rapid correction of dehydration. The oil microcapsules encapsulate electrolytes, preventing release into the stomach and avoiding hyperosmolar irritation such as nausea and vomiting. The invention provides a dedicated range of 265–280 mOsm / kg for rapid salt replenishment and gastrointestinal safety, while the microcapsule structure counteracts hyperosmolar stimulation. With a glucose concentration of 15–30 mmol / L (a 60%–80% reduction) and an osmotic pressure of 265–280 mOsm / kg (close to physiological human osmotic pressure), the fully formulated low-glycemic index formula is suitable for diabetic patients, infants, the elderly, and other special populations. It is applicable to various dehydration scenarios, including diarrhea-induced dehydration, heatstroke, exercise-induced dehydration, and mild postoperative dehydration. Attached Figure Description

[0020] Figure 1 This is a line graph comparing the serum sodium and potassium ion absorption rates of different formulations of the present invention (Examples 1-3 and Comparative Examples). Detailed Implementation

[0021] All embodiments of this invention follow the core principle: sugar alcohol components cannot activate the small intestinal SGLT-1 transporter protein, and the trace amounts of free glucose in the raw materials are impurities and do not reach the effective concentration. The replenishment channel is stably opened by adding a limited dose of anhydrous glucose (15-30 mmol / L for reconstitution); the remaining amount is made up to 100 parts by weight with erythritol. The preparation process adopts an equal-volume incremental low-speed mixing process to ensure uniform powder mixing, no particle breakage, and no material stratification.

[0022] Example 1: Mild and low-irritant formula for infants and young children (low sodium, low acid, ultra-low glycemic index, and rapid absorption advantages) Formula for a rapidly absorbed, low-irritation oral electrolyte rehydration solution (parts by weight, total 100 parts) 1.8 parts sodium chloride, 1.1 parts potassium chloride, 0.9 parts potassium malate, 3.2 parts L-alanine, 18 parts erythritol, 6 parts maltitol, 2.2 parts hydrogenated palm oil, 1.5 parts polydextrose, 0.4 parts malic acid, 0.7 parts anhydrous glucose; the remaining erythritol is added to make up to 100 parts.

[0023] Take 100 portions of the above-mentioned rapidly absorbed, low-irritation oral electrolyte rehydration solution composition and dissolve it in 250 mL of warm water. After rehydration, the glucose concentration is 15 mmol / L (SGLT-1 minimum effective activation concentration), and the osmotic pressure of the solution is 265 mOsm / kg.

[0024] In this formula, 100 parts by weight corresponds to the actual production specification of 12.5 g (net content of a single bag of finished product). That is, each small bag of oral powder weighs 12.5 grams. All 12.5 grams of powder is poured into 250 mL of warm water and mixed. After mixing, all indicators of the solution (glucose concentration, osmotic pressure, electrolyte concentration) strictly match the design values.

[0025] Conversion logic: 1 serving = 0.125g, the whole formula contains 100 servings, and the total weight is 12.5g / bag.

[0026] The specific preparation steps are as follows: 1. Raw material pretreatment All powdered auxiliary materials are sieved through an 80-100 mesh sieve to remove lumps, coarse particles, and mechanical impurities, ensuring uniform initial powder particle size. The relative humidity of the production environment is controlled to ≤35%, and the entire process is carried out in a low-humidity, closed environment to prevent sugar alcohols and electrolytes from absorbing moisture and agglomerating, thus providing the basic material conditions for subsequent precise classification and mixing.

[0027] 2. Preparation of acid-resistant microcapsule coating of ionic components Three ionic electrolyte raw materials, sodium chloride, potassium chloride, and potassium malate, were prepared in the prescribed amounts and mixed into powder to obtain a composite electrolyte powder. A molten hydrogenated palm oil spray coating process was used to completely encapsulate the composite electrolyte powder with the prescribed amount of hydrogenated palm oil as the wall material to prepare acid-resistant ion-isolated microcapsules.

[0028] This process can physically isolate electrolyte ions from organic acids and acidic environments within the system, effectively preventing ion precipitation, acid-base reactions, and component failure during storage. At the same time, it enables targeted release and gentle absorption into the intestines after preparation, significantly reducing oral and gastrointestinal irritation in infants and young children, thus aligning with the original design intent of low-acid and low-irritation formulas.

[0029] 3. Low-humidity, incrementally increasing premixing treatment of sugar alcohol systems This formulation system is characterized by low polydextrose content and extremely high proportions of erythritol and maltitol, making it highly susceptible to defects such as segregation of light components, moisture absorption and stratification, and uneven mixing. Therefore, a strict incremental doubling mixing process is adopted, with the ambient humidity ≤35% throughout the process, low-speed mixing, and prevention of shear damage. The specific operating steps are as follows: (1) First feeding and mixing: Premix: Erythritol (18 parts erythritol and 6 parts maltitol in this example) without the final replenishment amount is mixed evenly to obtain a mixed powder of erythritol and maltitol; Feeding: Add the total amount of polydextrose and anhydrous glucose according to the formula, and add erythritol and maltitol mixed powder equal to the total weight of the two materials mentioned above. Mix at a low speed of 15 r / min for 5 min. (2) Second volume expansion mixing: Add the remaining sugar alcohol mixed powder with the same total mass as the current system, and continue to mix at a low speed of 15 r / min for 5 min; (3) The material system is gradually expanded by adding the material in a cyclical manner. Each time, the mixture is slow-speed mixed at 15r / min for 5min until all the erythritol (excluding the final amount of erythritol) and all the maltitol in the formula are added and mixed to obtain a highly uniform, non-layered, and non-hygroscopic sugar alcohol composite premixed powder.

[0030] The entire process employs a low-speed, gentle mixing method at 15 r / min to avoid issues such as sugar alcohol particle breakage, powder electrostatic agglomeration, and thermal degradation of anhydrous glucose caused by high-speed shearing, thus ensuring the integrity of the low-glycemic index sugar alcohol structure and the stability of its physicochemical properties.

[0031] 4. Low-speed, low-shear overall mixing The prepared acid-resistant ion-isolating microcapsules, sugar alcohol premixed powder, L-alanine and malic acid were put into a three-dimensional mixer. Finally, the remaining amount of erythritol was added to make up the total mass to 100 parts. The mixing speed was set to 15 r / min, and the mixture was mixed at low shear and low speed for 10 to 15 min (15 min is used as an example in this embodiment) to obtain the final uniform composite functional powder.

[0032] The 15r / min low-speed mixing process can significantly reduce the stirring shear force, effectively prevent the active components of amino acids, organic acids, and sugars from being degraded by heat, and at the same time prevent microcapsule membrane damage and particle breakage, reduce powder electrostatic agglomeration and air entrainment, greatly improve the macroscopic and microscopic mixing uniformity of all components of the powder, and ensure the uniformity and stability of the finished powder.

[0033] 5. Aseptic and sealed direct packaging (unique process without granulation) This process involves no granulation, tableting, effervescence, or preparation of oral liquids. The mixed composite powder is directly packaged into oral powders in a low-humidity, clean, and sterile environment. The finished product structure consists of: acid-resistant ion-isolated microcapsules + sugar alcohol composite premixed matrix + functional active ingredients + the remainder is supplemented with erythritol for stabilization. The product is then sealed, protected from light and moisture, and the finished product is prepared.

[0034] This embodiment addresses the delicate digestive systems, low tolerance, and susceptibility to acidity and high ion stimulation in infants and young children. It employs an electrolyte-resistant microcapsule isolation technology, a low-moisture sugar alcohol gradient premixing technology, low-shear low-speed total mixing, and a granulation-free direct dispensing dry process to prepare oral solid dosage forms. The entire process avoids granulation, tableting, effervescence, and the preparation of oral liquids, thus circumventing existing dosage form patent barriers. Ion coating ensures electrolyte acid resistance and stability, preventing direct contact and reaction with organic acids. Gradient sugar alcohol mixing completely solves the problems of moisture absorption, stratification, and segregation in oligodextrose and high-sugar alcohol systems. The final product is a low-irritant rehydration powder with uniform composition, extremely high stability, excellent dissolving properties, and high tolerance in infants and young children.

[0035] Features of the formulation in this embodiment: This embodiment features a low-irritant formula specifically designed for infants and young children, using the lowest electrolyte, lowest acidity, and lowest glucose dosage within the formula range. The extremely low glucose content completely avoids issues such as blood sugar fluctuations and excessively high intestinal osmotic pressure in infants and young children. The weakly acidic system is gentle and does not irritate the gastrointestinal tract, reducing adverse reactions such as vomiting and bloating. The polyols provide a sweet, non-bitter taste, significantly improving medication compliance in infants and young children. It is suitable for mild diarrhea and routine dehydration rehydration in infants and young children, and is also safe for infants with glucose tolerance disorders. Through the combined effect of the two pathways, the intestinal absorption efficiency of infants and young children is improved compared to traditional ORSⅢ, and the onset time of rehydration is significantly shortened. The extremely low glucose content does not cause a rebound in intestinal osmotic pressure, preventing secondary water leakage, resulting in faster recovery from dehydration and a shorter duration of diarrhea. It is tailored to the delicate intestinal characteristics, weak absorption, and susceptibility to vomiting in infants and young children, achieving unexpected technical effects of gentle, zero-irritation, and rapid rehydration.

[0036] Example 2: A universally applicable balanced formula (optimal rapid absorption, preferred median formula) Formula for a rapidly absorbed, low-irritation oral electrolyte rehydration solution (parts by weight, total 100 parts) Sodium chloride 2.2 parts, potassium chloride 1.35 parts, potassium malate 1.1 parts, L-alanine 3.8 parts, erythritol 15 parts, maltitol 8 parts, hydrogenated palm oil 2.6 parts, polydextrose 2.0 parts, malic acid 0.6 parts, anhydrous glucose 0.9 parts; the remaining erythritol is added to make up to 100 parts.

[0037] Key parameters: Take 100 portions of the rapidly absorbed, low-irritation oral electrolyte rehydration solution and dissolve them in 250 mL of warm water. After rehydration, the glucose concentration is 20 mmol / L (the optimal activation concentration of SGLT-1), and the osmotic pressure of the solution is 272 mOsm / kg.

[0038] In this formula, 100 parts by weight corresponds to the actual production specification of 12.5 g (net content of a single bag of finished product). That is, each small bag of oral powder weighs 12.5 grams. All 12.5 grams of powder is poured into 250 mL of warm water and mixed. After mixing, all indicators of the solution (glucose concentration, osmotic pressure, electrolyte concentration) strictly match the design values.

[0039] Conversion logic: 1 serving = 0.125g, the whole formula contains 100 servings, and the total weight is 12.5g / bag.

[0040] The specific preparation steps are the same as in Example 1.

[0041] Key parameters: Dissolve 100 portions of the composition in 250 mL of warm water. After reconstitution, the glucose concentration is 20 mmol / L (the optimal activation concentration of SGLT-1), and the osmotic pressure of the solution is 272 mOsm / kg.

[0042] Formula characteristics: In this embodiment, the glucose concentration is 20 mmol / L, which is the optimal saturation activation concentration for SGLT-1. It is also combined with a median L-alanine content of 3.8 parts to maximize the activation of L-alanine's stepwise mediation of intestinal epithelial B-cell activation. 0 Type B neutral amino acid transport system (B 0 AT1) and its downstream basal-side amino acid transport system. The transport system achieves optimal balance through synergistic efficiency of the two pathways.

[0043] The specific effects of the rapid absorption technology in this embodiment are as follows: 1. 20 mmol / L glucose is just enough to completely saturate the SGLT-1 transporter, with no glucose waste, no osmotic pressure burden, and the absorption channels fully open; 2. Amino acid channels independently transport sodium ions, independent of glucose and not limited by sugar concentration, with both channels operating at full capacity simultaneously; 3. An osmotic pressure of 272 mOsm / kg is the optimal osmotic pressure range for intestinal absorption, where water molecules permeate across the membrane at the fastest rate. Compared to ORSⅢ: It eliminates intestinal osmotic resistance caused by high sugar; adds a completely new independent sodium absorption pathway; the overall fluid absorption rate is better than ORSⅢ, and the dehydration correction time is shortened by about 25%. It is the fastest and most stable balanced formula for recovery from daily diarrhea and exercise-induced dehydration.

[0044] This embodiment represents the optimal balanced formulation, with a balanced electrolyte ratio and stable rehydration efficiency. Trace amounts of glucose precisely activate the sodium-glucose cotransport pathway, achieving a rehydration rate comparable to ORSⅢ. The sugar alcohol compound system reduces glycemic load by more than 80%, catering to the general needs of children, adults, the elderly, and diabetic patients. It has moderate acidity and excellent taste, without the bitterness of traditional rehydration salts, making it suitable for most routine scenarios such as daily diarrhea, mild heatstroke, and exercise dehydration. This is the patented optimal industrial formulation.

[0045] Example 3: Adult high-intensity dehydration formula (high electrolytes, rapid fluid replacement, shortest recovery period) Formula for a rapidly absorbed, low-irritation oral electrolyte rehydration solution (parts by weight, total 100 parts) Sodium chloride 2.6 parts, potassium chloride 1.6 parts, potassium malate 1.3 parts, L-alanine 4.5 parts, erythritol 12 parts, maltitol 10 parts, hydrogenated palm oil 3.0 parts, polydextrose 2.5 parts, malic acid 0.8 parts, anhydrous glucose 1.35 parts; the remaining erythritol is added to make up to 100 parts.

[0046] Key parameters: Dissolve 100 portions of the rapidly absorbed, low-irritation oral electrolyte rehydration solution in 250 mL of warm water. After rehydration, the glucose concentration is 30 mmol / L (SGLT-1 maximum safe activation concentration), and the osmotic pressure of the solution is 280 mOsm / kg.

[0047] In this formula, 100 parts by weight corresponds to the actual production specification of 12.5 g (net content of a single bag of finished product). That is, each small bag of oral powder weighs 12.5 grams. All 12.5 grams of powder is poured into 250 mL of warm water and mixed. After mixing, all indicators of the solution (glucose concentration, osmotic pressure, electrolyte concentration) strictly match the design values.

[0048] Conversion logic: 1 serving = 0.125g, the whole formula contains 100 servings, and the total weight is 12.5g / bag.

[0049] The specific preparation steps are the same as in Example 1.

[0050] Key parameters: Dissolve 100 portions of the composition in 250 mL of warm water. After reconstitution, the glucose concentration is 30 mmol / L (SGLT-1 maximum safe activation concentration), and the osmotic pressure of the solution is 280 mOsm / kg. This embodiment is a high-electrolyte rapid recovery formula specifically designed for adults in high-intensity exercise, high-temperature work, and severe dehydration scenarios. It employs acid-resistant ion microcapsule isolation technology, low-moisture sugar alcohol incremental premixing technology, low-shear low-speed homogenization mixing, and a dry, direct-packaging process without granulation to prepare the oral powder. This process avoids granulation, tableting, effervescence, and the preparation of oral liquids, effectively circumventing existing patent barriers for rehydration formulations. Addressing the characteristics of this patented formula—low polydextrose content, high sugar alcohol content, and high electrolyte loading—a progressively incremental mixing process completely solves the problems of powder moisture absorption, stratification, and segregation. Simultaneously, oil microcapsule encapsulation mildens and stabilizes the high-salt system, eliminating gastrointestinal irritation while providing high electrolyte replenishment, achieving rapid rehydration and the shortest possible physical recovery period.

[0051] Formula characteristics: Advantages of rapidly absorbing core data: 1.30 mmol / L glucose completely saturates the SGLT-1 channel, and the sodium-glucose cotransport rate reaches the maximum value of this system; 2. High L-alanine content maximizes the activation of L-alanine-mediated intestinal epithelial B-cell pathways. 0 Type B neutral amino acid transport system (B 0 AT1 and its downstream basal amino acid transport system are independent of glucose, unaffected by intestinal damage, and can independently and rapidly absorb sodium and water. 3. Electrolyte ratio upper limit design to match the amount of ion loss in severe dehydration; 4. With an osmotic pressure of 280 mOsm / kg, it falls within the critical range for rapid absorption in the human intestinal tract, exhibiting the strongest osmotic driving force.

[0052] Final Implementation: In cases of moderate to severe dehydration, the fluid replenishment in this embodiment is significantly faster than that of ORSⅢ, and the dehydration correction cycle is shortened by more than 30%, thus addressing the technical shortcomings of existing ORSⅢ, such as slow onset of action, long recovery time, and insufficient fluid replenishment efficiency in cases of severe dehydration.

[0053] This embodiment is suitable for adults experiencing moderate to severe dehydration due to severe diarrhea, working in high-temperature environments, engaging in high-intensity exercise, or frequent vomiting. It uses an upper limit electrolyte ratio to quickly replenish lost sodium and potassium ions and correct electrolyte imbalances. It moderately increases the amount of glucose to maximize the activation of SGLT-1 transport efficiency and shorten the dehydration recovery time. Combined with high-content polydextrose and maltitol, it slows down intestinal osmotic pressure fluctuations, reduces persistent diarrhea, and strictly controls glucose concentration, resulting in no significant glycemic pressure. Adults with impaired glucose tolerance can safely take it for a short period.

[0054] Comparative example (existing ORSⅢ standard formulation) The conventional glucose-sodium citrate system was used, with an osmotic pressure of 240 mOsm / kg.

[0055] Comparative results: The electrolyte recovery time of the present invention is significantly shortened (as shown in Table 1), and gastrointestinal adverse reactions are reduced by more than 70%.

[0056] Table 1. Comparison of serum sodium and potassium ion absorption rates for different formulations of this invention. I. B 0 Other substrates available for AT1 (SLC6A19) B 0 AT1 is a broad-spectrum sodium-dependent transporter of neutral amino acids. In addition to L-alanine, it can also transport neutral amino acids such as leucine, isoleucine, valine, phenylalanine, methionine, and glutamine.

[0057] II. The core advantage of this formula is that it uses only L-alanine. 1. No channel competition with SGLT-1, enabling dual-channel coordinated transfer (most critical) Branched-chain amino acids such as leucine and valine partially interfere with the expression and transport efficiency of SGLT-1 transporter on the surface of intestinal epithelial cell membranes, resulting in competitive inhibition of the two pathways. L-alanine, however, does not compete for the binding site of SGLT-1; anhydrous glucose activates SGLT-1, and L-alanine activates B... 0 The two AT1 pathways operate independently, synchronously and in the same direction, driving sodium ion absorption without mutual antagonism. This is a core advantage that other amino acids cannot achieve.

[0058] Controllable osmotic pressure, suitable for low-osmotic formulation design Amino acids such as leucine and phenylalanine have low solubility, and adding the same amount will significantly increase the osmotic pressure of the system, making it impossible to achieve the low osmotic pressure (265-272 mOsm / kg) of this invention. L-alanine has excellent water solubility, and under the dosage range (3.2-4.5 parts), it has a very small contribution to the overall osmotic pressure. It can be used in combination with erythritol and maltitol to build a low glycemic index and low osmotic pressure system, which meets the safety requirements for use by infants and the general population.

[0059] Low metabolic load in the body, no risk of ammonia accumulation - Valine and leucine are prone to producing ammonia metabolites during metabolism. Dehydration reduces the body's metabolic capacity and can easily cause discomfort. L-alanine participates in the glucose-alanine cycle, has a gentle metabolic pathway, and can be directly converted into a small amount of energy without raising blood ammonia levels. It is safe for the elderly and infants. At the same time, it does not cause blood sugar fluctuations, perfectly matching the "ultra-low glycemic index" design purpose of the formula.

[0060] It exhibits strong compatibility and stability, and its powder processing technology enables microencapsulation. Most other neutral amino acids have poor chemical stability and are prone to oxidation and discoloration during processing and storage. They also react with malic acid in the formula in an acid-base reaction. L-alanine, however, has stable physicochemical properties and can be combined with inorganic salts to form acid-resistant microcapsules using hydrogenated palm oil. These microcapsules do not release in the stomach but instead activate B vitamins upon reaching the small intestine. 0 AT1 transport makes it difficult for other amino acids to complete the encapsulation process, and they are prone to premature dissolution and inactivation in the stomach.

[0061] This invention discloses a low-glycemic index compound oral rehydration solution suitable for all population groups. It achieves synergistic absorption of sodium and sugar by activating the SGLT-1 channel with a trace amount of glucose and replaces most of the glucose with a polyol system, thus taking into account both high-efficiency rehydration and low-glycemic index. The overall osmotic pressure of the formula after reconstitution is controlled at 265-280 mOsm / kg, which is superior to existing ORS formulas and is suitable for the general population as well as special populations such as diabetics and infants.

Claims

1. A rapidly absorbed, low-irritation oral electrolyte rehydration solid dosage form, characterized in that: The ingredients are included in parts by weight as follows: Electrolyte complex components: 1.8–2.6 parts sodium chloride, 1.1–1.6 parts potassium chloride, and 0.9–1.3 parts potassium malate; Amino acid synergistic absorption component: L-alanine 3.2–4.5 parts; Polyol matrix: 12-18 parts erythritol, 6-10 parts maltitol; Ion-isolated microcapsule wall material: 2.2–3.0 parts hydrogenated palm oil; Anti-caking stabilizer: 1.5–2.5 parts polydextrose; Acidity regulator: 0.4–0.8 parts malic acid; SGLT1 activator: 0.675–1.35 parts of anhydrous glucose; The remaining amount was made up to 100 parts with erythritol.

2. The rapidly absorbed, low-irritation oral electrolyte rehydration solid preparation according to claim 1, characterized in that: The glucose concentration of the oral electrolyte rehydration solution solid preparation, which is rapidly absorbed after reconstitution and has low irritation, is controlled at 15–30 mmol / L; the osmotic pressure is 265–280 mOsm / kg.

3. A method for preparing a rapidly absorbed, low-irritation oral electrolyte rehydration solid dosage form as described in claim 1, characterized in that: The specific preparation steps are as follows: (1). Preprocessing All powder raw materials are passed through an 80-100 mesh sieve to remove agglomerated particles; (2). Ion microcapsule coating Sodium chloride, potassium chloride, and potassium malate were mixed evenly and then coated with molten hydrogenated palm oil to obtain acid-resistant ion-isolated microcapsules. (3). Premixed sugar alcohol system Erythritol, maltitol, polydextrose, and anhydrous glucose were added and mixed in equal amounts in sequence. (4). Total mixture The acid-resistant ion-isolated microcapsules obtained in step (2), the sugar alcohol system premix obtained in step (3), L-alanine, and malic acid were put into a three-dimensional mixer. Finally, the remaining amount of erythritol in the formula was added to make up the total mass to 100 parts. The mixture was mixed at low speed to obtain a uniform composite powder. (5) Aseptic dispensing The composite powder obtained in step (4) is directly packaged into oral powder.

4. The method for preparing a rapidly absorbed, low-irritation oral electrolyte rehydration solid dosage form according to claim 3, characterized in that: The specific operation sequence of the equal-quantity incremental mixing process in step (3) is as follows: 1) Add all the polydextrose, anhydrous glucose, and an equal weight of erythritol and maltitol powder, and mix at a low speed of 15 r / min for 5 min. 2) Add the remaining erythritol and maltitol mixed powder equal to the total weight of the current mixed powder, and mix well; continue to double the amount until all the erythritol and maltitol mixed powder except for the replenished amount of erythritol has been added. Each time you mix, the low speed stirring speed is 15r / min and the stirring time is 5min.

5. The preparation method of the rapidly absorbed, low-irritation oral electrolyte rehydration solid dosage form according to claim 3, characterized in that: In step (4), the mixing speed of the low-speed stirring is 15 r / min, and the mixing time is 5 to 15 min.

6. The method for preparing a rapidly absorbed, low-irritation oral electrolyte rehydration solid dosage form according to claim 3, characterized in that: In steps (1) to (5), the ambient humidity is ≤35%, and erythritol maintains its crystal flowability under the humidity conditions.

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