Iron fumarate biotin oral liquid and preparation method thereof

Abstract

This application discloses an iron-nicotinic acid-biotin oral solution and its preparation method, belonging to the field of pharmaceutical technology. The oral solution is composed of sodium ferrous citrate, nicotinamide, D-biotin, modified sea cucumber polypeptide iron chelate, hyaluronic acid, citric acid, sweetener, and flavoring. Using chitosan-encapsulated sea cucumber polypeptide iron chelate as the iron source significantly improves iron bioavailability and intestinal absorption efficiency, while reducing the gastrointestinal irritation of traditional iron supplements. By combining nicotinamide and D-biotin, synergistic supplementation of the three nutrients—iron, nicotinic acid, and biotin—is achieved, making it suitable for the prevention and adjunctive treatment of iron deficiency anemia and vitamin deficiencies. The preparation process includes dissolving, mixing, filtering, pH adjustment, and sterilization. The conditions are mild, the operation is simple, the resulting product has good stability, a pleasant taste, and high safety for long-term consumption.

Description

Technical Field

[0001] This application belongs to the field of pharmaceutical technology, specifically relating to an iron nicotinic acid biotin oral solution and its preparation method. Background Technology

[0002] Iron deficiency is a global problem. When iron is deficient, the amount of hemoglobin synthesized by red blood cells decreases, leading to smaller red blood cells, reduced oxygen-carrying capacity, and iron-deficiency anemia. Studies have shown a close relationship between iron and immunity; iron can enhance the body's immunity, increase the phagocytic function of neutrophils and phagocytes, and also strengthen the body's resistance to infection. According to foreign research literature, the impact of early childhood iron-deficiency anemia on brain development is irreversible, and behavioral changes in children are unrelated to the severity of anemia. Iron-deficiency anemia poses a significant threat to children's health, making its prevention and treatment particularly important.

[0003] Niacin, also known as vitamin PP or vitamin B3, is a collective term for nicotinic acid, nicotinamide, and derivatives with nicotinamide bioactivity. The primary physiological function of niacin is as a basic component of coenzymes, participating in cellular metabolic processes. The main form of niacin in the blood is nicotinamide. Early studies found that niacin deficiency pellagra can be accompanied by neurological symptoms such as depression, apathy, headache, fatigue, and memory loss. Recent studies have provided a deeper understanding of the neuroprotective effects of niacin, especially nicotinamide. Nicotinamide is a commonly used source of niacin supplementation, helping to maintain healthy skin and mucous membranes, is an essential component of energy metabolism, and also helps maintain a healthy nervous system. It plays a role in the prevention and treatment of oral and systemic diseases through multiple mechanisms of action, including inhibiting microbial growth, supplementing intracellular NAD+ levels, inhibiting the activity of key enzymes such as PARP, regulating cellular immune responses, and enhancing DNA repair capabilities. Niacin deficiency can cause skin erythema, burning and itching, and oozing, followed by the formation of herpes and bullae, then crusting, pigmentation, roughness, and scaling.

[0004] Biotin, also known as vitamin B7, participates in gluconeogenesis, the synthesis of fatty acids, and the metabolism of certain amino acids. It also promotes the synthesis of certain proteins through energy production and conversion; assists in cell health and regeneration; enhances the body's immune function; improves the health of sweat glands, nerve tissue, bone marrow, and male gonads; maintains normal skin and hair function; alleviates symptoms of eczema and dermatitis; relieves muscle pain; alleviates depression and insomnia; and promotes urea synthesis and excretion. It can be used as an adjunct treatment for arteriosclerosis, stroke, lipid metabolism disorders, hypertension, coronary heart disease, and circulatory disorders.

[0005] Currently, there is no oral liquid on the market that can simultaneously supplement iron, niacin, and biotin. Therefore, there is an urgent need for an oral liquid that can simultaneously supplement iron, niacin, and biotin, be directly and quickly absorbed and utilized by the human body, be less susceptible to interference from other ingredients or substances, and improve bioavailability. Summary of the Invention

[0006] In order to simultaneously supplement iron, niacin, and biotin, the purpose of this application is to provide an iron-niacin-biotin oral solution, which combines sodium ferrous citrate, niacinamide, D-biotin, modified sea cucumber polypeptide iron chelate, hyaluronic acid, citric acid, sweetener, and flavoring to provide a safe oral solution for simultaneously supplementing iron, niacin, and biotin, enhancing iron absorption, and improving bioavailability.

[0007] The purpose of this application is also to provide a method for preparing ferricyanoid biotin oral solution, which has mild conditions, simple process and can effectively prepare oral solution.

[0008] To achieve the above objectives, this application provides a ferricyanide biotin oral solution and its preparation method, which is implemented using the following technical solution: On one hand, this application provides an iron nicotinic acid biotin oral solution, which is composed of the following raw materials: 5-10g sodium ferrous citrate, 0.45-0.95g nicotinamide, 1.5-4.5mg D-biotin, 0.1-2g modified sea cucumber polypeptide iron chelate, 1-3mg hyaluronic acid, 2-7g citric acid, 0.1-1.0g sweetener, 0.1-0.5mL flavoring, and purified water to make up to 1L.

[0009] Preferably, the modified sea cucumber polypeptide iron chelate is a chitosan-encapsulated sea cucumber polypeptide iron chelate.

[0010] Preferably, the sweetener is any one of sucralose, steviol glycoside, mogroside-erythritol complex, wherein the mogroside-erythritol complex is obtained by mixing mogroside and erythritol in a weight ratio of 1:1.

[0011] This application provides an iron-nicotinic acid-biotin oral solution, which consists of chitosan-encapsulated sea cucumber polypeptide iron chelates. Chitosan acts as a carrier to protect the sea cucumber polypeptide iron chelates from degradation, while promoting their absorption in the intestine and improving the bioavailability of iron. The combination of nicotinamide and D-biotin simultaneously supplements iron, nicotinic acid, and biotin. Sea cucumber peptides are typically composed of 2 to 20 amino acids, have high bioavailability, and are more easily absorbed than the original protein. Sea cucumber peptides have antioxidant and anti-aging effects and improve the bioavailability of iron. Hyaluronic acid can protect against intestinal mucosal irritation.

[0012] On the other hand, this application provides a method for preparing ferricyanide biotin oral solution, the method comprising the following steps: (1) Add citric acid to purified water and mix to obtain a citric acid solution; (2) Take purified water into a mixing tank, heat to boiling, add sodium ferrous citrate and heat to boiling with saturated steam, add sweetener, stir, cool to 30-60℃, add nicotinamide solution and D-biotin solution prepared in advance, mix and stir to obtain oral liquid intermediate; (3) Add modified sea cucumber polypeptide iron chelate and hyaluronic acid to the oral liquid intermediate, mix and stir, filter through a titanium rod to a dispensing tank, add purified water and stir evenly, adjust the pH value to 2.5-6.5 with 20%-40% citric acid solution, add flavoring, stir evenly to obtain a medicine solution, filter the medicine solution through a filter element, titanium rod and pleated membrane, fill and seal to obtain the oral liquid semi-finished product; wherein, the temperature of the medicine solution is 20-40℃; (4) The oral liquid semi-finished product is sterilized, inspected by light, packaged and put into storage to obtain the finished iron nicotinic acid biotin oral liquid.

[0013] Preferably, the heating and boiling time in step (2) is 10 to 60 minutes.

[0014] Preferably, the pre-insulation temperature in step (2) is 25-45°C.

[0015] Preferably, the filter material in step (3) is a stainless steel metal filter element with a filtration accuracy of 5 to 30 µm; the titanium rod has a filtration accuracy of 1 to 20 µm and the pleated membrane has a filtration accuracy of 0.10 to 0.45 µm.

[0016] Preferably, the modified sea cucumber polypeptide iron chelate in step (3) is prepared by mixing sea cucumber polypeptide iron chelate powder with chitosan in a mass ratio of 1:2 to obtain the modified sea cucumber polypeptide iron chelate.

[0017] Preferably, the preparation method of the sea cucumber peptide iron chelate powder is as follows: sea cucumber peptide and ferrous chloride are mixed at a mass ratio of 4:1, purified water is added, the pH of the solution is adjusted to 6.0, the reaction is carried out for 40 min, and the reaction temperature is 60℃ to prepare the sea cucumber peptide iron chelate. The sea cucumber peptide iron chelate powder is obtained by centrifugation purification and freeze-drying.

[0018] Preferably, the sterilization in step (4) is moist heat sterilization, wherein the parameters are temperature 100-115℃, 20-50min.

[0019] The beneficial effects of the embodiments in this application are as follows: (1) For the first time, three key nutrients, iron (sodium ferrous citrate), niacin (nicotinamide) and biotin (D-biotin), are scientifically combined in a single formulation to achieve efficient synergistic supplementation. The core ingredient, "modified sea cucumber polypeptide iron chelate encapsulated in chitosan", uses chitosan as a carrier to protect the iron chelate from degradation in the gastrointestinal tract and promote its targeted absorption in the intestine, thereby significantly improving the bioavailability and absorption efficiency of iron.

[0020] (2) By using the above-mentioned chitosan encapsulation technology and organic iron source (sea cucumber peptide iron chelate), the gastrointestinal irritation common in traditional iron supplements is effectively reduced, and patients' medication compliance and tolerance are greatly improved.

[0021] (3) Long-term stability tests show that the product remains highly stable in color, odor, state and the contents of iron, nicotinamide and D-biotin. Test data show that it is safe and non-toxic for long-term use. Detailed Implementation

[0022] The technical solutions of this application will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments in this application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of this application.

[0023] In the following examples, sea cucumber peptide and ferrous chloride were purchased from Sinopharm Chemical Reagent Co., Ltd.; sodium ferrous citrate, nicotinamide, D-biotin and hyaluronic acid were purchased from Sinopharm Chemical Reagent Co., Ltd.; other raw materials and reagents not specifically mentioned were all commercially available.

[0024] Example 1 Preparation of ferricyanide biotin oral solution (1) Ingredients: 5g sodium ferrous citrate, 0.45g nicotinamide, 1.5mg D-biotin, 0.1g modified sea cucumber polypeptide iron chelate, 1mg hyaluronic acid, 2g citric acid, 0.1g sucralose, 0.1mL flavoring.

[0025] (2) Preparation method: 1) Preparation of modified sea cucumber peptide iron chelate powder: a. Preparation of sea cucumber peptide iron chelate powder: Sea cucumber peptide and ferrous chloride were mixed at a mass ratio of 4:1 and purified water was added to prepare a purified aqueous solution with a peptide mass fraction of 0.1%. The pH of the solution was adjusted to 6.0, and the mixture was reacted in a water bath at 60 ℃ for 40 min. After the reaction, 4 times the volume of anhydrous ethanol was added for ethanol precipitation for 2 h. The precipitate was then centrifuged at 5000 r / min for 15 min. The precipitate was freeze-dried to obtain sea cucumber peptide iron chelate powder. b. Dissolve 2% w / v chitosan in 0.1% acetic acid and adjust the pH to 5.5; c. Prepare a 0.5% w / v sodium tripolyphosphate (TPP) solution; d. Under magnetic stirring at 800 rpm, the TPP solution is added dropwise to the chitosan solution to form an ionic gel.

[0026] e. Add the sea cucumber peptide iron chelate powder to the system and continue stirring for 30 minutes to obtain the modified sea cucumber peptide iron chelate powder; f. Characterization of the modified sea cucumber peptide iron chelate powder: its particle size is 90-130 nm and its encapsulation efficiency is >85%.

[0027] 2) Preparation of D-Biotin solution: Add 1.5 mg of D-Biotin to 10 mL of preheated purified water at 25 °C and mix. Stir and keep warm in a 25 °C water bath (Note: D-Biotin needs to be fully dissolved at 25–45 °C).

[0028] 3) Preparation of nicotinamide solution: Add 0.45g of nicotinamide to 10mL of purified water preheated at 25℃ and mix. Stir and keep warm in a 25℃ water bath (it should be explained that nicotinamide needs to be fully dissolved at 25-45℃).

[0029] 4) Preparation of ferricyanide biotin oral solution: a. Take 5g of citric acid and add it to 10mL of purified water to obtain a citric acid solution; b. Take 400 mL of purified water into a mixing tank, heat to boiling, add 5 g of sodium ferrous citrate and heat to boiling for 10 min with saturated steam, add 0.1 g of sucralose, stir, cool to 30 °C, add nicotinamide solution and D-biotin solution kept at 25 °C, mix and stir to obtain oral liquid intermediate. c. Add 0.1g of modified sea cucumber polypeptide iron chelate and 1mg of hyaluronic acid to the oral liquid intermediate, mix and stir, filter through a titanium rod to a dispensing tank, add purified water and stir evenly, adjust the pH value to 2.5 with 40% citric acid solution, add 0.1mL of flavoring, stir evenly, and add purified water to 1L to obtain the drug solution. d. The liquid medicine is filtered through a stainless steel metal filter element with a filtration accuracy of 5µm, a titanium rod with a filtration accuracy of 1µm, and a pleated membrane with a filtration accuracy of 0.10µm. The mixture is then filled and sealed to obtain a semi-finished oral liquid product. The temperature of the liquid medicine is 20℃.

[0030] e. The semi-finished oral liquid is sterilized by moist heat at 100℃ for 20 minutes, inspected by light, packaged, and stored to obtain the finished iron nicotinic acid biotin oral liquid.

[0031] Example 2 Preparation of ferricyanide biotin oral solution (1) Ingredients: 7g sodium ferrous citrate, 0.75g nicotinamide, 3mg D-biotin, 1g modified sea cucumber polypeptide iron chelate, 2mg hyaluronic acid, 4g citric acid, 0.3g steviol glycosides, 0.2mL flavoring.

[0032] (2) Preparation method: 1) Preparation of modified sea cucumber peptide iron chelate powder: Same as in Example 1.

[0033] 2) Preparation of D-Biotin solution: Add 3 mg of D-Biotin to 20 mL of purified water preheated at 35 °C and mix. Stir and keep warm in a 35 °C water bath (it should be explained that D-Biotin needs to be fully dissolved at 25–45 °C).

[0034] 3) Preparation of nicotinamide solution: Add 0.75g of nicotinamide to 20mL of purified water preheated at 35℃ and mix. Stir and keep warm in a 35℃ water bath (it should be explained that nicotinamide needs to be fully dissolved at 25-45℃).

[0035] 4) Preparation of ferricyanide biotin oral solution: a. Take 4g of citric acid and add it to 20mL of purified water to obtain a citric acid solution; b. Take 400 mL of purified water into a mixing tank, heat to boiling, add 7 g of sodium ferrous citrate and heat to boiling for 30 min with saturated steam, add 0.3 g of steviol glycoside, stir, cool to 30 °C, add nicotinamide solution and D-biotin solution kept at 35 °C, mix and stir to obtain oral liquid intermediate; c. Add 1g of modified sea cucumber polypeptide iron chelate and 2mg of hyaluronic acid to the oral liquid intermediate, mix and stir, filter through a titanium rod to a dispensing tank, add purified water and stir evenly, adjust the pH value to 4.5 with 20% citric acid solution, add 0.2mL of flavoring, stir evenly, and add purified water to 1L to obtain the drug solution. d. The liquid medicine is filtered through a stainless steel metal filter element with a filtration accuracy of 20µm, a titanium rod with a filtration accuracy of 10µm, and a pleated membrane with a filtration accuracy of 0.25µm. The mixture is then filled and sealed to obtain a semi-finished oral liquid product. The temperature of the liquid medicine is 30℃.

[0036] e. The semi-finished oral liquid is sterilized by moist heat at 100℃ for 30 minutes, inspected by light, packaged, and stored to obtain the finished ferricyanic acid biotin oral liquid.

[0037] Example 3 Preparation of ferricyanide biotin oral solution (1) Ingredients: 10g sodium ferrous citrate, 0.95g nicotinamide, 4.5mg D-biotin, 2g modified sea cucumber polypeptide iron chelate, 3mg hyaluronic acid, 7g citric acid, 1g mogroside erythritol complex (0.5g mogroside + 0.5g erythritol complex), 0.5mL flavoring.

[0038] (3) Preparation method: 1) Preparation of modified sea cucumber peptide iron chelate powder: Same as in Example 1.

[0039] 2) Preparation of D-Biotin solution: Add 4.5 mg of D-Biotin to 30 mL of purified water preheated at 45 °C, stir and keep warm in a 45 °C water bath (it should be explained that D-Biotin needs to be fully dissolved at 25-45 °C).

[0040] 3) Preparation of nicotinamide solution: Add 0.95g of nicotinamide to 30mL of purified water preheated at 45℃ and mix. Stir and keep warm in a 45℃ water bath (it should be explained that nicotinamide needs to be fully dissolved at 25-45℃).

[0041] 4) Preparation of ferricyanide biotin oral solution: a. Take 7g of citric acid and add it to 40mL of purified water to mix, and obtain a citric acid solution; b. Take 400 mL of purified water into a mixing tank, heat to boiling, add 10 g of sodium ferrous citrate and heat to boiling for 60 min with saturated steam, add 1 g of mogroside erythritol complex, stir, cool to 30 °C, add nicotinamide solution and D-biotin solution kept at 45 °C, mix and stir to obtain oral liquid intermediate. c. Add 2g of modified sea cucumber polypeptide iron chelate and 3mg of hyaluronic acid to the oral liquid intermediate, mix and stir, filter through a titanium rod to a dispensing tank, add purified water and stir evenly, adjust the pH value to 6.5 with 30% citric acid solution, add 0.5mL of flavoring, stir evenly, and add purified water to 1L to obtain the drug solution. d. The liquid medicine is filtered through a stainless steel metal filter element with a filtration accuracy of 30µm, a titanium rod with a filtration accuracy of 20µm, and a pleated membrane with a filtration accuracy of 0.45µm. The mixture is then filled and sealed to obtain a semi-finished oral liquid product. The temperature of the liquid medicine is 40℃.

[0042] e. The semi-finished oral liquid is sterilized by moist heat at 100℃ for 30 minutes, inspected by light, packaged, and stored to obtain the finished ferricyanic acid biotin oral liquid.

[0043] Comparative Example 1 Preparation of iron-free nicotinic acid biotin oral solution (1) Ingredients: 0.45g nicotinamide, 1.5mg D-biotin, 1mg hyaluronic acid, 2g citric acid, 0.1g sucralose, 0.1mL flavoring.

[0044] (2) Preparation method: 1) Preparation of D-Biotin solution: Same as in Example 1.

[0045] 2) Preparation of nicotinamide solution: Same as in Example 1.

[0046] 3) Preparation of ferricyanide biotin oral solution: a. Take 5g of citric acid and add it to 10mL of purified water to obtain a citric acid solution; b. Take 400 mL of purified water into a mixing tank, heat to boiling, add 0.1 g of sucralose, stir, cool to 30 °C, add nicotinamide solution and D-biotin solution kept at 25 °C, mix and stir to obtain oral liquid intermediate; c. Add 1 mg of hyaluronic acid to the oral liquid intermediate, mix and stir, filter through a titanium rod to a mixing tank, add purified water and stir evenly, adjust the pH to 2.5 with 40% citric acid solution, add 0.1 mL of fragrance, stir evenly, and add purified water to 1 L to obtain the drug solution. d. The liquid medicine is filtered through a stainless steel metal filter element with a filtration accuracy of 5µm, a titanium rod with a filtration accuracy of 1µm, and a pleated membrane with a filtration accuracy of 0.10µm. The mixture is then filled and sealed to obtain a semi-finished oral liquid product. The temperature of the liquid medicine is 20℃.

[0047] e. The oral liquid semi-finished product is sterilized by moist heat at 100℃ for 20 minutes, inspected by light, packaged, and put into storage to obtain the finished oral liquid product.

[0048] Comparative Example 2 Preparation of iron nicotinic acid biotin oral solution (unmodified sea cucumber polypeptide iron chelate, hyaluronic acid) (1) Ingredients: 5g sodium ferrous citrate, 0.45g nicotinamide, 1.5mg D-biotin, 2g citric acid, 0.1g sucralose, 0.1mL flavoring.

[0049] (2) Preparation method: 1) Preparation of D-Biotin solution: Same as in Example 1.

[0050] 2) Preparation of nicotinamide solution: Same as in Example 1.

[0051] 3) Preparation of ferricyanide biotin oral solution: a. Take 5g of citric acid and add it to 10mL of purified water to obtain a citric acid solution; b. Take 400 mL of purified water into a mixing tank, heat to boiling, add 5 g of sodium ferrous citrate and heat to boiling for 10 min with saturated steam, add 0.1 g of sucralose, stir, cool to 30 °C, add nicotinamide solution and D-biotin solution kept at 25 °C, mix and stir to obtain oral liquid intermediate. c. Add purified water to the oral liquid intermediate and stir well. Adjust the pH to 2.5 with 40% citric acid solution, add 0.1 mL of flavoring, stir well, and add purified water to 1 L to obtain the drug solution. d. The liquid medicine is filtered through a stainless steel metal filter element with a filtration accuracy of 5µm, a titanium rod with a filtration accuracy of 1µm, and a pleated membrane with a filtration accuracy of 0.10µm. The mixture is then filled and sealed to obtain a semi-finished oral liquid product. The temperature of the liquid medicine is 20℃.

[0052] e. The oral liquid semi-finished product is sterilized by moist heat at 100℃ for 20 minutes, inspected by light, packaged, and put into storage to obtain the finished oral liquid product.

[0053] Comparative Example 3 Preparation of ferricyanide biotin oral solution (D-Biotin-free) (1) Ingredients: 5g sodium ferrous citrate, 0.45g nicotinamide, 0.1g modified sea cucumber polypeptide iron chelate, 1mg hyaluronic acid, 2g citric acid, 0.1g sucralose, 0.1mL flavoring.

[0054] (2) Preparation method: 1) Preparation of modified sea cucumber peptide iron chelate powder: Same as in Example 1.

[0055] 2) Preparation of nicotinamide solution: Same as in Example 1.

[0056] 3) Preparation of ferricyanide biotin oral solution: a. Take 5g of citric acid and add it to 10mL of purified water to obtain a citric acid solution; b. Take 400 mL of purified water into a mixing tank, heat to boiling, add 5 g of sodium ferrous citrate and heat to boiling for 10 min with saturated steam, add 0.1 g of sucralose, stir, cool to 30 °C, add nicotinamide solution kept at 25 °C, mix and stir to obtain oral liquid intermediate; c. Add 0.1g of modified sea cucumber polypeptide iron chelate and 1mg of hyaluronic acid to the oral liquid intermediate, mix and stir, filter through a titanium rod to a dispensing tank, add purified water and stir evenly, adjust the pH value to 2.5 with 40% citric acid solution, add 0.1mL of flavoring, stir evenly, and add purified water to 1L to obtain the drug solution. d. The liquid medicine is filtered through a stainless steel metal filter element with a filtration accuracy of 5µm, a titanium rod with a filtration accuracy of 1µm, and a pleated membrane with a filtration accuracy of 0.10µm. The mixture is then filled and sealed to obtain a semi-finished oral liquid product. The temperature of the liquid medicine is 20℃.

[0057] e. The oral liquid semi-finished product is sterilized by moist heat at 100℃ for 20 minutes, inspected by light, packaged, and put into storage to obtain the finished oral liquid product.

[0058] Comparative Example 4 Preparation of ferricyanide biotin oral solution (nicotinamide-free) (1) Ingredients: 5g sodium ferrous citrate, 1.5mg D-biotin, 0.1g modified sea cucumber polypeptide iron chelate, 1mg hyaluronic acid, 2g citric acid, 0.1g sucralose, 0.1mL flavoring.

[0059] (2) Preparation method: 1) Preparation of modified sea cucumber peptide iron chelate powder: Same as in Example 1.

[0060] 2) Preparation of D-Biotin solution: Same as in Example 1.

[0061] 3) Preparation of ferricyanide biotin oral solution: a. Take 5g of citric acid and add it to 10mL of purified water to obtain a citric acid solution; b. Take 400 mL of purified water into a mixing tank, heat to boiling, add 5 g of sodium ferrous citrate and heat to boiling for 10 min with saturated steam, add 0.1 g of sucralose, stir, cool to 30 °C, add D-biotin solution kept at 25 °C, mix and stir to obtain oral liquid intermediate. c. Add 0.1g of modified sea cucumber polypeptide iron chelate and 1mg of hyaluronic acid to the oral liquid intermediate, mix and stir, filter through a titanium rod to a dispensing tank, add purified water and stir evenly, adjust the pH value to 2.5 with 40% citric acid solution, add 0.1mL of flavoring, stir evenly, and add purified water to 1L to obtain the drug solution. d. The liquid medicine is filtered through a stainless steel metal filter element with a filtration accuracy of 5µm, a titanium rod with a filtration accuracy of 1µm, and a pleated membrane with a filtration accuracy of 0.10µm. The mixture is then filled and sealed to obtain a semi-finished oral liquid product. The temperature of the liquid medicine is 20℃.

[0062] e. The oral liquid semi-finished product is sterilized by moist heat at 100℃ for 20 minutes, inspected by light, packaged, and put into storage to obtain the finished oral liquid product.

[0063] Test case (1) Test materials: Take the test samples of Examples 1-3 and Comparative Examples 1-4.

[0064] (2) Test methods and data: The samples from Examples 1-3 were placed at room temperature and subjected to strong light irradiation. The samples were placed under an illuminance of (4500±500) lx. The color, taste, odor, state and pH value of the oral liquid were examined on the same day (October), January, February and March. The results were compared with those in October, as shown in Table 1. The iron, nicotinamide and D-biotin content of the samples from Examples 1-3 and Comparative Examples 1-4 were tested, and the results are shown in Table 2.

[0065] Table 1 Stability Test

[0066] Table 2. Content of iron, nicotinamide, and D-biotin

[0067] (3) Experimental results: According to Table 1 and Table 2, the color, taste, odor, state and pH value of the oral liquids of Examples 1-3 are relatively stable. The iron, nicotinamide and D-biotin contents of Examples 1-3 are higher than those of the comparative examples.

[0068] Experimental Example 2 Iron absorption test (1) Experimental materials: oral liquids of Example 1 and Comparative Example 2; iron deficiency anemia rat model, provided by Jiangsu Hanjiang Biotechnology Co., Ltd.

[0069] (2) Grouping: The rat model was randomly divided into 3 groups: Model control group (given an equal volume of purified water); Comparative Group 2 (administered Comparative Group 2 oral solution); Example 1 group (administered with the oral solution of Example 1); Normal control group (no modeling).

[0070] (3) Experimental methods: The drug was administered by gavage once a day for 4 consecutive weeks. The model control group was given an equal volume of purified water. Hematological indicators: Hemoglobin (Hb), red blood cell count (RBC), and hematocrit (HCT) were detected before administration (week 0), 2 weeks after administration, and 4 weeks after administration. Iron metabolism indicators: At the end of the experiment, blood was collected to separate serum and the serum iron (SI) and serum ferritin (SF) levels were detected.

[0071] (4) Experimental results: 1) In Example 1, Hb, RBC, and HCT levels at 2 weeks, 4 weeks, and 2 weeks after drug withdrawal were significantly higher than in Comparative Example 2. Two weeks after drug withdrawal: the average Hb level was 132 g / L, close to the normal control group's 141 g / L; the average RBC level was 6.32 × 10⁻⁶. 12 / L, close to the normal control group of 6.52×10 12 / L; the average HCT was 38%, close to the normal control group's 40%, while the average Hb in the two comparative groups was 96 g / L; the average RBC was 4.15 × 10 12 / L; the average HCT was 28%, which was significantly lower than that of the normal control group; therefore, the iron absorption efficiency of Example 1 was significantly better than that of Comparative Example 2, in which the model group had the following characteristics: average Hb was 67 g / L; average RBC was 3.26 × 10¹² / L; and average HCT was 20%.

[0072] 2) SI detection results: The average value of SI in Example 1 group was 1.5 mg / L, which is close to the normal control group's 1.7 mg / L; the average value of SF detection results was 92 ng / mL, which is close to the normal control group's 126 ng / mL; the average value of SI in Comparative Example 2 group was 0.8 mg / L; the average value of SF detection results was 76 ng / mL; SI, SF content and iron absorption rate were also significantly higher than those in Comparative Example 2 group, proving that modified sea cucumber polypeptide iron chelate can significantly improve the intestinal absorption efficiency of iron. Among them, the model group had: SI: 0.6 mg / L; SF: 33 ng / mL.

[0073] 3) Gastrointestinal tolerance: The incidence of diarrhea and constipation in the Example 1 group was significantly lower than that in the Comparative Example 2 group, proving that chitosan encapsulation technology and hyaluronic acid can reduce the gastrointestinal irritation of iron supplements.

[0074] Experimental Example 3 Long-term toxicity test (1) Experimental animals: SPF-grade SD (Sprague-Dawley) rats, provided by Jiangsu Hanjiang Biotechnology Co., Ltd., half male and half female; age and weight: 6 weeks old, female weight 180-220g, male weight 220-260g; housing environment: temperature 20-26℃, relative humidity 40%-70%, 12h light and dark alternation, free access to food and water.

[0075] (2) Experimental grouping and administration: Rats were randomly divided into 4 groups, with 20 rats in each group (10 males and 10 females): Blank control group: given an equal volume of purified water; Low-dose group: Administered an oral solution equivalent to 5 times the recommended human dose; Medium-dose group: Administered an oral solution equivalent to 20 times the recommended human dose; High-dose group: Administered an oral solution equivalent to 50 times the recommended human dose; Administration method: Oral gavage, once daily, for 6 consecutive months.

[0076] (3) Detection indicators: 1) General clinical observation: The appearance, behavior, activity, secretions, excrement and mortality of the animals were observed daily. Their weight was measured and food intake was recorded weekly. Their behavior was no different from that of the blank control group, and their feeding and excretion were normal. 2) Hematological examination: Blood samples were collected from the orbital venous plexus at 3 months, 6 months after drug administration, and during the recovery period (4 weeks after drug withdrawal). Red blood cell count, hemoglobin, and platelet count were consistent with the control group. The average values ​​for each indicator were: Red blood cell count during the recovery period: 8.1 × 10⁶ / µL; Hemoglobin: 13.5 g / dL; Platelet count: 7.3 × 10⁶ / µL. 5 / µL.

[0077] 3) Histopathological examination: After the experiment, all animals were euthanized and underwent systematic autopsies. Each organ was carefully observed for any abnormalities. The heart, liver, spleen, lungs, kidneys, adrenal glands, brain, testes / ovaries, stomach, intestines, and lymph nodes were paraffin-embedded, sectioned, and stained with hematoxylin and eosin (HE). Under a light microscope, no morphological changes were observed, and no damage was found. (3) Experimental results: When taken for a long period of time at a dose far exceeding the recommended human dosage, the oral liquid of this application did not produce obvious toxic reactions in rats. All physiological and biochemical indicators remained within the normal range, and there was no pathological damage to the major organs, proving the safety of long-term consumption.

[0078] In summary, the iron niacin biotin oral solution and its preparation method provided in this application, through the rational combination of active ingredients such as sodium ferrous citrate, nicotinamide, D-biotin, and modified sea cucumber polypeptide iron chelate, simultaneously supplements iron, nicotinamide, and D-biotin, making it suitable for the prevention and adjunctive treatment of iron niacin biotin deficiency. The examples and comparative data show that the product of this application exhibits excellent stability, content retention, and sensory quality, high safety for long-term consumption, and high bioavailability.

[0079] Although embodiments of this application have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of this application. All equivalent changes and improvements made within the scope of this application shall still fall within the patent coverage of this application.

Claims

1. A ferricyanide biotin oral solution, characterized in that, The oral liquid is composed of the following ingredients: 5-10g sodium ferrous citrate, 0.45-0.95g nicotinamide, 1.5-4.5mg D-biotin, 0.1-2g modified sea cucumber polypeptide iron chelate, 1-3mg hyaluronic acid, 2-7g citric acid, 0.1-1.0g sweetener, 0.1-0.5mL flavoring, and purified water to a final volume of 1L.

2. The ferricyanide biotin oral solution as described in claim 1, characterized in that, The modified sea cucumber polypeptide iron chelate is a chitosan-encapsulated sea cucumber polypeptide iron chelate.

3. The ferricyanide biotin oral solution as described in claim 1, characterized in that, The sweetener is any one of sucralose, steviol glycoside, mogroside erythritol complex, wherein the mogroside erythritol complex is obtained by mixing mogroside and erythritol in a weight ratio of 1:

1.

4. A method for preparing an oral solution of ferricyanide biotin, characterized in that, The method includes the following steps: (1) Add citric acid to purified water and mix to obtain a citric acid solution; (2) Take purified water into a mixing tank, heat to boiling, add sodium ferrous citrate and heat to boiling with saturated steam, add sweetener, stir, cool to 30-60℃, add nicotinamide solution and D-biotin solution prepared in advance, mix and stir to obtain oral liquid intermediate; (3) Add modified sea cucumber polypeptide iron chelate and hyaluronic acid to the oral liquid intermediate, mix and stir, filter through a titanium rod to a dispensing tank, add purified water and stir evenly, adjust the pH value to 2.5-6.5 with 20%-40% citric acid solution, add flavoring, stir evenly to obtain a medicine solution, filter the medicine solution through a filter element, titanium rod and pleated membrane, fill and seal to obtain the oral liquid semi-finished product; wherein, the temperature of the medicine solution is 20-40℃; (4) The oral liquid semi-finished product is sterilized, inspected by light, packaged and put into storage to obtain the finished iron nicotinic acid biotin oral liquid.

5. The preparation method of the ferricyanide biotin oral solution as described in claim 4, characterized in that, The heating and boiling time in step (2) is 10 to 60 minutes.

6. The preparation method of the ferricyanide biotin oral solution as described in claim 4, characterized in that, The pre-insulation temperature mentioned in step (2) is 25-45℃.

7. The preparation method of the ferricyanide biotin oral solution as described in claim 4, characterized in that, The filter material in step (3) is a stainless steel metal filter element with a filtration accuracy of 5 to 30 µm; the titanium rod has a filtration accuracy of 1 to 20 µm and the pleated membrane has a filtration accuracy of 0.10 to 0.45 µm.

8. The preparation method of the ferricyanide biotin oral solution as described in claim 4, characterized in that, The modified sea cucumber polypeptide iron chelate described in step (3) is prepared by mixing sea cucumber polypeptide iron chelate powder with chitosan at a mass ratio of 1:2 to obtain the modified sea cucumber polypeptide iron chelate.

9. The method for preparing a ferricyanide biotin oral solution as described in claim 8, characterized in that, The preparation method of the sea cucumber peptide iron chelate powder is as follows: sea cucumber peptide and ferrous chloride are mixed at a mass ratio of 4:1, purified water is added, the pH of the solution is adjusted to 6.0, the reaction is carried out for 40 min, and the reaction temperature is 60℃ to prepare sea cucumber peptide iron chelate. After centrifugation purification and freeze drying, sea cucumber peptide iron chelate powder is obtained.

10. The preparation method of the ferricyanide biotin oral solution as described in claim 4, characterized in that, The sterilization described in step (4) is moist heat sterilization, wherein the parameters are temperature 100-115℃, 20-50min.

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