Symbiotic, sweetened low-osmolarity oral rehydration salt (ORS) containing zinc and L-glutamine.

Abstract

The utility model is a low-osmolarity rehydration composition designed in powder form for oral administration. The composition includes sodium chloride, potassium chloride, trisodium citrate, glucose, zinc gluconate, L-glutamine, Lactobacillus rhamnosus GG, inulin, stevia, and natural flavor, and is stabilized with maltodextrin as a carrier. When dissolved in 200 mL of drinking water, it provides an osmolality of approximately 240–245 mOsm / L. The product is suitable for use in cases of diarrhea and dehydration and exhibits a symbiotic effect.

Description

SYMBIOTIC, SWEETENED LOW-CAKE CONTAINING ZINC AND L-GLUTAMINE. ORAL REHYDRATION SALT WITH OSMOLARITY (ORS) Technical Area The utility model is for oral rehydration salt (ORS) formulations, particularly in acute diarrhea. This relates to the use of low osmolarity ORS solutions. WHO (World Health Organization) Since 2004, low osmolarity ORS mixture has been used instead of standard ORS mixture. It recommends its use in the treatment of all types of diarrhea in all age groups. Our useful model. symbiotic oral rehydration saline solution conforming to the latest recommended standards (prebiotic + probiotic), with well-known supplemental ingredients such as amino acids, zinc, and sweeteners. It is related to a new, enriched composition. State of the Art Diarrhea is a major health problem worldwide, particularly in low- and middle-income countries. Diarrhea is a cause of morbidity and mortality. It causes fluid and electrolyte loss from the body in patients of all age groups. By causing losses, it disrupts the body's biochemical balance and can lead to kidney failure, heart failure, and other health problems. This can lead to cognitive impairment, confusion, and even shock and death. Globally, approximately 1.7 to 2 billion cases of diarrhea are reported each year. This number... It is mostly concentrated in children under 5 years of age (WHO – Global Health Estimates, 2023). As of 2022, approximately 500,000 people worldwide die each year due to diarrhea. It is losing [number] lives. Approximately 446,000 of these deaths occur among children under the age of 5. (UNICEF & WHO – Child Health Epidemiology Reference Group (CHERG), 2023). This The vast majority of deaths are due to lack of clean water, sanitation, hygiene, and timely oral rehydration. Diarrhea can be prevented with oral respiration (ORS) treatment. According to the WHO, when ORS use reaches 100% accessibility, diarrhea will be prevented. Child mortality related to ORS can be reduced by up to 93%. (Munos MK et al. (2010), Effect of ORS on diarrhea mortality BMC Public Health) To treat diarrhea and the fluid and electrolyte losses it causes, the World Health Organization (WHO) classic (standard) oral rehydration solution (ORS) from the 1980s to 2003 The use of formulated salts has been recommended. In this classic formula, one liter contains: Sodium chloride (NaCl) 3.5 g, sodium bicarbonate (or sodium citrate) 2.5 g (or 2.9 g sodium citrate), Potassium chloride (KCl) at a dose of 1.5 g and glucose (anhydrant) at 20.0 g, with an osmolarity of... It is approximately 311 mOsm / L. However, studies conducted in 2002 and 2003 have shown this to be higher. Osmolarity can increase stool volume in some patients, especially children, and osmotic 1 Since it was seen that it could create a burden, the WHO developed a new low-osmolarity formulation in 2003. They have accepted it and started making recommendations. WHO Low Osmolarity ORS Formulation (Per 1 Liter of Water): Component Quantity (grams) Purpose Sodium chloride (NaCl) 2.6 g compensates for the loss of sodium and chloride. Trisodium citrate dihydrate 2.9 g provides a base in place of bicarbonate, corrects acidosis. Potassium chloride (KCl) 1.5 g provides potassium and chloride. Glucose (anhydrous) 13.5 g increases sodium absorption and provides energy. Total 20.5 g The electrolyte values ​​in this formulation are: Electrolyte Concentration (mmol / L) Sodium (Na⁺) 75 mmol / L Chloride (Cl⁻) 65 mmol / L Potassium (K⁺) 20 mmol / L Citrate 10 mmol / L Glucose 75 mmol / L Total osmolarity ~245 mOsm / L This new low-osmolarity ORS formula, when dissolved in one liter of water, produces approximately 245 mOsm / L. By providing osmolarity, it establishes the optimal water absorption balance. Current ORS preparations on the market effectively treat dehydration. However, it has limited capabilities in areas such as shortening the duration of diarrhea or accelerating intestinal recovery. It has an effect. For example, even with low osmolarity, the standard ORS formula may contain diarrhea-related substances. It does not contain components that repair mucosal damage or provide probiotic microflora support. In the known state of the technique, zinc supplementation is used in addition to ORS in the treatment of diarrhea. It is recommended because the duration and severity of zinc supplementation are particularly important in childhood diarrhea. It has been scientifically shown to reduce [the effects of zinc]. In practice, zinc is usually taken in separate tablets or syrups. It is supplied in this form. In addition, it is available in ready-made powder formulations containing a combination of ors + zinc. It is in use. Similarly, the use of probiotics (especially species such as Lactobacillus rhamnosus GG) Benefits of shortening diarrhea duration and regulating intestinal flora in acute gastroenteritis. It is known that probiotics are also generally considered separate products from ORS. Although it is offered elsewhere, it is also found in combined products containing orthodontic acid and probiotics. Some on the market 2 Although some ORS products contain prebiotic fiber (e.g., inulin) or sweeteners / flavorings, these are also... It has limited content and is usually focused on a single benefit (e.g., taste improvement only). (for purposes). The amino acid L-glutamine plays a role in the regeneration of the intestinal epithelium and in the intestinal It is known to strengthen the barrier; however, this amino acid is not present in existing ORS powders. He won't take it. To date, in the known state of the technology, all these components – zinc, symbiotic (prebiotic) + probiotic), L-glutamine and sweetener combined, and also compliant with WHO low-fat formula. There is no ORS composition that meets the osmolarity standard. Our utility model is a structured system with specific ratios, aiming for enhanced clinical impact. composition, the specific ratio of the components, target osmolarity, dissolution volume, With its harmonious component ratios and child-friendly aromatic structure, the new product has a technical impact. It is a combination of food supplements. This deficiency, which is not currently in use, allows users to... Treatment of diarrhea requires the use of multiple supplements, which affects the effectiveness of the treatment. and can negatively affect patient compliance and lead to higher treatment costs. is happening. As a result, our new composition provides not only hydration but also... A multicomponent, low-osmolarity agent targeting gastrointestinal and immune functions. It is a solution. The utility model offers a single sachet for the treatment of dehydration caused by diarrhea. It helps with fluid and electrolyte replacement, as well as nutritional and microbial support. This eliminates the need to use multiple products, thus reducing usage. Ease of use and increased efficiency are achieved. The Purpose of a Utility Model The aim of this useful model is to treat and rehydrate diarrhea in a single formulation. The aim is to increase both effectiveness and practicality by combining them. The topic of the utility model has been strengthened. The ORS formulation provides fluid-electrolyte balance to standard low-osmolarity ORS. While maintaining its functionality, it aims to provide the following advantages thanks to the added components: • Shortening the duration of diarrhea: Zinc and Lactobacillus rhamnosus GG added to the formulation. Probiotics reduce infection and inflammation in the gut, thereby decreasing the duration and severity of diarrhea. It helps to reduce it. 3 • Repair of intestinal mucosa: The amino acid L-glutamine is the main component of small intestinal enterocytes. It is a source of energy and promotes faster regeneration of the intestinal wall damaged by diarrhea. supports. • Supporting the balance of beneficial microbiota: Lactobacillus rhamnosus GG, pathogenic. By replacing microorganisms, it promotes the re-establishment of a healthy gut flora. Inulin prebiotic, on the other hand, helps this probiotic to adhere and multiply in the intestine. It provides a symbiotic effect by offering support. • Improved taste and patient compliance: Natural sweetener derived from the stevia plant. And natural fruit flavors (orange, lemon, etc.) enhance the taste of the prepared solution. This makes child patients, in particular, more willing to consume ORS. This, in turn, increases the success of the treatment. It is critical for implementation. Detailed Description of the Utility Model The formulation of the utility model is in addition to the WHO (World Health Organization) low osmolarity ORS basic composition. It is formulated by integrating specific supplementary substances. Below, 200 ml The components and quantities contained in a sachet composition prepared to dissolve in water. listed. • Sodium chloride (NaCl): 350 mg– (Source of sodium and chloride ions; essential for rehydration) electrolyte.) 20. Potassium chloride (KCl): 300 mg – (Source of potassium and chloride ions; rehydration and electrolyte) (for balance.) • Trisodium citrate dihydrate: 580 mg– (Citric acid salt; helps correct metabolic acidosis) It provides a base source and additional sodium. In the WHO formulation, it replaces sodium bicarbonate. (It is used.) 25• Anhydrous Glucose: 2700 mg – (Pure glucose without monohydrate; sodium absorption) (A carbohydrate source that facilitates and provides energy.) • Zinc gluconate: 35 mg – (Provides 5 mg of elemental zinc. Zinc is essential for epithelium) Zinc is a critical trace element for cell regeneration and immune function. It is also used in the treatment of diarrhea. (This support has a shortening effect on the duration of diarrhea, especially in children.) 30• L-Glutamine: 250 mg – (L-glutamine amino acid in free form. Intestinal mucosa) It has been added for repair and nourishment. By supporting cell regeneration, it helps with diarrhea. (It accelerates the healing of intestinal damage.) • Lactobacillus rhamnosus GG: ≥1× 10⁹ CFU – (Live probiotic bacteria culture, at least 1 There will be billions of colony-forming units. This bacteria settles in the gastrointestinal system. 4 It reduces the duration of diarrhea by competing with pathogens and exhibiting anti-inflammatory effects. GG This strain is clinically proven to have probiotic efficacy and safety. It is lyophilized in the formula. (It is available in freeze-dried powder form.) • Inulin: 400 mg – (A plant-derived fructo-oligosaccharide prebiotic dietary fiber. In the intestine) It is not digested but fermented by beneficial bacteria such as Lactobacillus; thus It supports the multiplication and persistence of probiotic bacteria. It also retains water in the intestines, reducing stool volume. (It can help regulate the consistency.) • Stevia extract: 15 mg – (Contains steviol glycosides derived from the Stevia Rebaudiana plant.) It is a natural, calorie-free sweetener. This amount provides a noticeable sweetness in the solution by neutralizing glucose. It masks the slightly salty taste, but its contribution to osmolarity is negligible. (Does not disrupt the low osmolarity balance of the formulation.) • Fruit flavor: 50 mg – (Food-grade orange essence, for example. The solution has a pleasant citrus aroma) And it makes it taste good. (It especially makes it easier for children to drink ORS willingly.) • Maltodextrin (bulking agent and carrier) in sufficient quantity (approximately 120 mg) 15• Our utility model's osmolarity calculations (for 200 mL): This technical calculation was prepared according to the low osmolarity ORS criterion. The total osmotic charge created when our composition is dissolved in 200 mL of water. This shows that, according to the World Health Organization (WHO) criteria, the low osmolarity limit is 250. The reading is mOsm / L, which means a maximum osmotic load of 50 mOsm for 200 mL. Below A calculation table based on the osmotic contributions of the formula components is presented. Component mg ​​Molecular weight mmol Particle size 200 mL (g / mol) mOsm Sodium 350 58.44 5.989 2 11.98 chloride (NaCl) Potassium 300 74.55 4.024 2 8.05 chloride (KCl) Trisodium 580 294.1 1.972 4 7.89 citrate dihydrate Anhidrosis 2700 180.16 14.987 1 14.99 glucose Zinc 35 455.68 0.077 2 0.15 gluconate L-glutamine 250 146.14 1.711 1 1.71 Inulin 400 5000.0 0.08 1 0.08 Stevia 15 805.0 0.019 1 0.02 Fruit 50 500.0 0.1 1 0.1 aroma Probiotic + 320 5000.0 0.064 1 0.06 carrier maltodextrin Total osmotic load (for 200 mL of solution): approximately 45.03 mOsm This value conforms to the WHO low osmolality criterion (≤50 mOsm / 200 mL). When prepared with 200 mL of solution, this sachet containing the composition will hold approximately 240–245 ml. It has an osmolarity of mOsm / L. It is compliant with the WHO's low osmolarity ORS standard. Although the WHO comparison in terms of technical compliance was made on a 1-liter basis, this product in practice It is dosed according to 200 mL of solution and is commercially available in single-use sachets. It is presented. Furthermore, the formulation that is the subject of the utility model is designed to dissolve in 200 mL of drinking water. It can also be prepared in effervescent tablet form. This preparation uses citric acid and sodium bicarbonate. Food-compatible additives such as those mentioned can be used. The effervescent form has the same ratio and content. It offers the advantages of resolution and portability. All formulation variants containing these components that provide low osmolarity when dissolved, Regardless of the dissolution volume, it is included within the scope of the utility model. Areas of Application The subject of the utility model is ORS supplementation, primarily for acute gastroenteritis (diarrhea). It has been developed for use in cases of dehydration, especially in children under 5 years of age. Improving rehydration therapy is key in infectious diarrheas such as those seen with rotavirus. The goal is to support oral fluid intake in the treatment of diarrhea while also addressing the underlying condition. 6 It aims to shorten the duration and reduce complications. It also treats severe diarrhea, such as in cholera. It can also be used in cases of illnesses, traveler's diarrhea, and food poisoning. Similarly, in adults, this formulation is used for sporadic acute diarrhea or severe diarrhea. In cases of fluid loss due to sweating (e.g., athletes or heatstroke), oral medication is recommended. It can be used for rehydration purposes. In the form of medical nutritional support, it helps maintain intestinal integrity. It is important to be under the supervision of a doctor even in chronic conditions such as short bowel syndrome. It has the potential for implementation. The utility model involves prescription drugs in pharmacies or healthcare facilities. or it may be offered as an over-the-counter dietary supplement. Thanks to its flavor-enhancing ingredients. It is particularly suitable for use in pediatric patients and is included in home diarrhea treatment programs. It can be prepared. The contents of one sachet, usually 200 ml, can be boiled according to the instructions on the package. It is added to chilled water, stirred until completely dissolved, and given to the patient in small sips. It is given to drink. After each watery stool and at regular intervals according to signs of thirst. The solution is continued to be used. Industrial Applicability: The utility model can be easily produced in existing food and pharmaceutical industry facilities. It has the characteristics to be applicable to industry. Raw material components required for production. (glucose, salts, amino acids, probiotic cultures, etc.) are commercially available and standard. They are subject to quality control. Mixers and dosing devices used for preparing powder mixtures. Packaging machines are commonly found in facilities that produce food supplements. The formulation's production process does not require any special or new equipment; therefore They can be integrated into existing production lines. Disposable sachet packaging for food and pharmaceuticals. It is manufactured and used from moisture and light barrier foil material, which is a standard in its sector. Industrial-scale packaging of the product is possible. The product is not only in chassis form. It can also be produced as effervescent tablets by following the necessary process. Both forms comply with GMP (Good Manufacturing Practice) standards. (Applications) can be put into mass production in accordance with the conditions. As a result, the utility model, It is technologically feasible and commercially viable, and its applicability to industry is... It is available. 7

Claims

1. Instructions: 200 mL to drink, used for rehydration and supporting bowel health. A low-osmolarity oral rehydration solution prepared in powder form to be dissolved in water. Its composition and characteristic is; - 350 mg sodium chloride (NaCl), - 300 mg potassium chloride (KCl), - 580 mg trisodium citrate dihydrate, - 2700 mg anhydrous glucose, - 35 mg zinc gluconate (an amount that will provide approximately 5 mg of elemental zinc), - 250 mg L-glutamine, - Lactobacillus rhamnosus GG in amounts ≥1×10⁹ CFU, - 400 mg inulin (prebiotic), - 15 mg stevia, - 50 mg natural fruit flavor It contains maltodextrin and is supported by it as a carrier.

2. The oral rehydration composition specified in Claim 1 is characterized by its ability to maintain probiotic viability. It contains Lactobacillus rhamnosus GG in lyophilized (freeze-dried) form for preservation purposes.

3. The oral rehydration composition specified in Claim 1, characterized by its consistency in 200 mL of water. When dissolved, it has a total osmolarity of approximately 240–245 mOsm / L.

4. The oral rehydration composition specified in Claim 1 is characterized by its symbiotic properties. by showing that it contains both probiotics (Lactobacillus rhamnosus GG) and prebiotics (inulin) It includes.

5. The oral rehydration composition specified in Claim 1 is characterized by 250 mg L-glutamine. It includes.

6. The oral rehydration composition specified in Claim 1 is used for acute diarrhea in children and adults. It is characterized by its suitability for use as a supportive treatment for dehydration.

7. The oral rehydration composition specified in Claim 1, with effervescent carrier components. Formulated with citric acid and sodium bicarbonate, which have an effect, in effervescent tablets. It is characterized by the fact that it can be prepared in this form. 8