An oral preparation for improving anemia after a gastrectomy operation and a preparation method thereof

Abstract

The present application provides an oral preparation for improving anemia after gastrectomy and a preparation method thereof, and relates to the technical field of biological medicine. The oral preparation comprises the following raw materials: vitamin B 12 , intrinsic factor, chickpea protein, collagen type III peptide, pH regulator, antioxidant and dispersing agent. The present application takes vitamin B 12 and intrinsic factor as active ingredients, significantly improves the utilization degree of vitamin B 12 through a specific ratio of the two, and the prepared reagent meets the requirements of not releasing in the stomach acid environment and then slowly releasing in the intestinal tract, has a significant effect on the anemia problem caused by vitamin B 12 deficiency after gastrectomy, and has high drug stability.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, specifically to an oral preparation for improving anemia after gastrectomy and its preparation method. Background Technology

[0002] Therapeutic resection is an effective treatment for localized gastric cancer. Postoperative anemia, including megaloblastic anemia and iron deficiency anemia, is common in patients after gastrectomy. Anemia can affect postoperative wound healing. It is frequently detected perioperatively and in the early postoperative period, but there are no standard treatments, such as iron supplementation regimens. Current literature largely focuses on nutritional support during the surgical period, with limited research on long-term nutritional therapy after gastrectomy. Severe iron deficiency anemia after gastrectomy may cause atrophy of the small intestinal villi and vitamin B1 deficiency. 12 It can correct megaloblastic anemia after gastrectomy, which can cause an imbalance in the CD4 / CD8 ratio and a decrease in the activity of natural killer cells.

[0003] Vitamin B 12 A deficiency will lead to megaloblastic anemia, a type of anemia caused by impaired deoxyribonucleic acid (DNA) synthesis, primarily due to a deficiency of vitamin B. 12 It may be caused by folic acid, or by acquired DNA synthesis disorders due to heredity or drugs. (From *Intermediate Medical Journal*, 1985, Issue 4, Vitamin B1) 12 Hu Xianya publicly disclosed the clinical application and evaluation of vitamin B. 12 It is used clinically as an "external factor" to combat pernicious anemia. "Life's Ark, the Nemesis of Pernicious Anemia, Wen Yue" discloses Vitamin B. 12 It is an organic compound with cobalt as its core element. With cobalt, vitamin B... 12 Only then can hematopoietic function be developed.

[0004] Intrinsic factor is closely related to pernicious anemia in adolescents. W.B. Castle (1927) proposed that the effective factor for treating pernicious anemia requires the combination of a certain component in food—extrinsic factor—and a necessary component in gastric juice—intrinsic factor—for absorption and red blood cell maturation. Extrinsic factor is vitamin B1. 12 Vitamin B 12 It is mainly obtained from animal-based foods, and its absorption and conversion involve a series of complex steps, including: Vitamin B... 12 It separates from food and forms a complex with R-protein in the stomach. This complex is then digested by pancreatic enzymes in the upper small intestine, releasing vitamin B1. 12 It is transferred to intrinsic factor, forming intrinsic factor-vitamin B. 12 The complex binds to ileal cell receptors, enters the cell via endocytosis, and binds to transcobalamin II. Transcobalamin II then transfers vitamin B...12 Delivered to the tissue. Intrinsic factor can be seen in vitamin B... 12 It plays an important role in the absorption process.

[0005] Intrinsic factor deficiency can cause vitamin B deficiency 12 Deficiency occurs after total gastrectomy, when all cells secreting intrinsic factor are lost. Without intervention, patients will inevitably develop vitamin B deficiency. 12 Megaloblastic anemia due to deficiency. Vitamin B deficiency may also occur in patients who have undergone partial gastrectomy. 12 Deficiency. Small intestinal bacterial imbalance can also cause megaloblastic anemia in patients after gastrectomy. In the early stages of megaloblastic anemia, symptoms may be solely due to folic acid or vitamin B deficiency. 12 Deficiency is not uncommon clinically. Intrinsic factor and vitamin B... 12 Combination is B 12 Essential factors for intestinal absorption.

[0006] However, due to the partial or complete loss of all cells secreting intrinsic factor after gastrectomy, there is currently little research on the treatment of vitamin B deficiency after gastrectomy. 12 Anemia caused by deficiency can be treated with vitamin B supplementation. 12 The document discusses using intrinsic factor to address this issue. This is because, on the one hand, it is necessary to solve the problem of intrinsic factor denaturation in the acidic environment of the stomach; on the other hand, relying solely on passive diffusion results in low absorption rates and insignificant efficacy. Furthermore, it is necessary to meet the conditions of maintaining integrity in the acidic environment of the stomach and achieving sustained intestinal release.

[0007] Therefore, it is necessary to develop a product based on vitamin B. 12 Developing pharmaceutical formulations with intrinsic factor as the active ingredient to meet the needs of preventing or treating megaloblastic anemia after gastrectomy is a pressing technical problem for researchers in this field. Furthermore, the stability of intrinsic factor needs to be addressed. Summary of the Invention

[0008] To address the aforementioned problems, this invention provides an oral preparation for improving anemia after gastrectomy and its preparation method. The preparation has high stability, remains intact in the acidic environment of the stomach (pH 1-3), and is released slowly into the intestine (pH 6-7), thus meeting the needs of a wide range of patients undergoing gastrectomy.

[0009] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0010] On one hand, the present invention provides an oral preparation for improving anemia after gastrectomy, comprising the following ingredients: vitamin B1 12 Intrinsic factor, chickpea protein, type III collagen peptides, pH adjusters, antioxidants, and dispersants.

[0011] Preferably, the vitamin B 12 The mass ratio of the intrinsic factor to the intrinsic factor is 1:1-2.

[0012] More preferably, the vitamin B 12 The mass ratio of the intrinsic factor to the intrinsic factor is 1:1.2-1.8.

[0013] More preferably, the vitamin B 12 The mass ratio of the intrinsic factor to the intrinsic factor is 1:1.5.

[0014] Preferably, the pH adjuster is selected from at least one of malic acid, ferulic acid, citric acid, tartaric acid, and fumaric acid.

[0015] More preferably, the pH adjuster is selected from at least one of malic acid and ferulic acid.

[0016] More preferably, the pH adjuster is malic acid and ferulic acid.

[0017] Preferably, the mass ratio of malic acid to ferulic acid is 4-6:2-4.

[0018] More preferably, the mass ratio of malic acid to ferulic acid is 5:3.

[0019] Preferably, the antioxidant is selected from at least one of grape seed extract, epigallocatechin gallate (EGCG), gallic acid, and vitamin E.

[0020] More preferably, the antioxidant is selected from at least one of grape seed extract and epigallocatechin gallate (EGCG).

[0021] More preferably, the antioxidant is grape seed extract and epigallocatechin gallate (EGCG).

[0022] Preferably, the mass ratio of grape seed extract to epigallocatechin gallate (EGCG) is 1-3:1.

[0023] More preferably, the mass ratio of the grape seed extract to epigallocatechin gallate (EGCG) is 2:1.

[0024] Preferably, the dispersant is selected from at least one of Morinda officinalis polysaccharide, mannitol, and ferulic acid.

[0025] More preferably, the dispersant is Morinda officinalis polysaccharide, mannitol, and ferulic acid.

[0026] Preferably, the mass ratio of Morinda officinalis polysaccharide, mannitol, and ferulic acid is 3-5:10-15:0.5-1.5.

[0027] More preferably, the mass ratio of Morinda officinalis polysaccharide, mannitol, and ferulic acid is 4:12:1.

[0028] Preferably, the product comprises, by weight, the following ingredients: 1-3 parts vitamin B1 12 2-6 parts intrinsic factor, 30-40 parts chickpea protein, 5-10 parts type III collagen peptides, 5-12 parts pH adjuster, 1-5 parts antioxidant and 12-20 parts dispersant.

[0029] More preferably, the product comprises, by weight parts, the following ingredients: 1-2 parts vitamin B. 12 2-3 parts intrinsic factor, 32-38 parts chickpea protein, 6-9 parts type III collagen peptides, 5-10 parts pH adjuster, 1-4 parts antioxidant and 15-20 parts dispersant.

[0030] More preferably, by weight, it comprises the following ingredients: 2 parts vitamin B 12 3 parts intrinsic factor, 35 parts chickpea protein, 8 parts type III collagen peptides, 8 parts pH adjuster, 3 parts antioxidant and 17 parts dispersant.

[0031] Preferably, the raw materials further include acetate buffer and β-cyclodextrin.

[0032] More preferably, the mass of the β-cyclodextrin is equal to that of vitamin B1. 12 8-10 times.

[0033] Secondly, the present invention provides a method for preparing the above-mentioned oral formulation, comprising the following steps:

[0034] S1: Intrinsic factor is mixed with chickpea protein and type III collagen peptides and swollen in acetate buffer for 20-40 min to obtain a composite carrier;

[0035] S2: Vitamin B 12 After inclusion, it is mixed with the composite carrier to obtain mixture 1;

[0036] S3: Mixture 1, pH adjuster, antioxidant and dispersant are mixed and granulated.

[0037] Preferably, in step S1, the pH of the acetate buffer solution is 2.8-3.2.

[0038] More preferably, in step S1, the pH of the acetate buffer solution is 3.0.

[0039] Preferably, in step S1, the total mass of the intrinsic factor, chickpea protein, and type III collagen peptide is in a mass-to-volume ratio of 1g to 2-3mL of the acetate buffer.

[0040] Preferably, in step S1, the swelling time is 20-30 minutes and the temperature is 50-60°C. More preferably, in step S1, the swelling time is 30 minutes and the temperature is 55°C.

[0041] Preferably, in step S2, the inclusion complex consists of: vitamin B 12 Mix with 8-10 times the mass of β-cyclodextrin and mix at 35-40℃ for 1.5-2 hours to form microsphere inclusion complexes.

[0042] More preferably, in step S2, the inclusion complex consists of: Vitamin B1 12 Mixed with 10 times its mass of β-cyclodextrin, and mixed at 38°C for 2 hours, a microsphere inclusion complex was formed.

[0043] Preferably, in step S3, the mixing is carried out in the following order: mixture 1, pH adjuster, antioxidant, and dispersant.

[0044] Preferably, in step S3, the pH adjuster adjusts the pH to 1.5-2.5.

[0045] Compared with the prior art, the present invention has the following beneficial effects:

[0046] 1. This invention uses vitamin B 12 With intrinsic factor as the active ingredient, and through a specific ratio of the two, vitamin B2 can be significantly enhanced. 12 The availability of the reagents, prepared with specific raw materials, ensures their integrity in the gastric acid environment (pH=1-3) and slow release in the intestine (pH=6-7), specifically addressing the vitamin B deficiency following gastrectomy. 12 It has a significant effect on anemia caused by deficiency.

[0047] 2. The present invention significantly improves the stability of the prepared oral formulation by the synergistic effect of the active ingredients, pH adjuster, and antioxidant grape seed extract and epigallocatechin gallate (EGCG).

[0048] 3. This invention uses chickpea protein and type III collagen peptides as carriers to achieve the dual effects of nutrient absorption and mucosal repair, thereby further improving the efficacy of oral preparations.

[0049] 4. This invention uses a mixture of Morinda officinalis polysaccharide, mannitol, and ferulic acid as a dispersant to inhibit vitamin B12. 12 The aggregation of these substances further enhances the stability of the formulation. Detailed Implementation

[0050] To make the technical means, creative features, achieved objectives, and effects of this invention readily understandable, the invention is further illustrated below with specific embodiments. However, these embodiments are merely preferred embodiments and not all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments described herein without creative effort are all within the scope of protection of this invention. It is worth noting that the raw materials used in this invention are all common commercially available products, and their sources are not specifically limited. The technical and scientific terms used in the embodiments have the meanings commonly understood by those skilled in the art to which this invention pertains.

[0051] Intrinsic factor: Recombinant human intrinsic factor, sequence shown below, synthesized by WuXi AppTec Co., Ltd.

[0052] LFGQVLKDIVEKISMKIKDNGIIGDIYSTGLAMQALSVTPEPSKKEWNCKKTTDMILNEIKQGKFHNPMSIAQILPSLKGKTYLDVPQVTCSPDHEVQPTLPSNPGPG PTSASNITVIYTINNQLRGVELLFNETINVSVKSGSVLLVVLEEAQRKNPMFKFETTMTSWGLVVSSINNIAENVNHKTYWQFLSGVTPLNEGVADYIPFNHEHITAN.

[0053] Morinda officinalis polysaccharide: purchased from Xi'an Yuze Biotechnology Co., Ltd.

[0054] Type III collagen peptides: purchased from Jiangsu Caiwei Biotechnology Co., Ltd.

[0055] Chickpea protein: purchased from Tsinghua Biotechnology (Shanxi) Co., Ltd.

[0056] Grape seed extract: purchased from Xi'an Changhong Biotechnology Co., Ltd.

[0057] The oral formulation prepared in this invention contains vitamin B. 12 The dosage is 500 μg / tablet, and the intrinsic factor dosage is 20 mg / tablet. It is recommended to take one tablet once a day with a meal.

[0058] Example 1

[0059] An oral preparation for improving anemia after gastrectomy:

[0060] Includes the following ingredients: 2 servings of Vitamin B 12 3 parts intrinsic factor, 35 parts chickpea protein, 8 parts type III collagen peptide, 8 parts pH adjuster, 3 parts antioxidant, 17 parts dispersant, 20 parts β-cyclodextrin and 130 mL acetate buffer.

[0061] The pH adjuster consists of 5 parts malic acid and 3 parts ferulic acid; the antioxidant consists of 2 parts grape seed extract and 1 part EGCG; and the dispersant consists of 4 parts Morinda officinalis polysaccharide, 12 parts mannitol and 1 part ferulic acid.

[0062] The preparation method is as follows:

[0063] S1: Intrinsic factor was mixed with chickpea protein and type III collagen peptides and swollen in acetate buffer at pH 3.0 at 55°C for 30 min to obtain a composite carrier;

[0064] S2: Vitamin B 12 Mixed with β-cyclodextrin, the mixture was mixed at 38°C for 2 hours to form a microsphere inclusion complex, which was then mixed with the composite carrier obtained in step S1 to obtain mixture 1;

[0065] S3: Mixture 1, pH adjuster (adjust pH to 2.0), antioxidant and dispersant are added in sequence, mixed, granulated and tableted.

[0066] Example 2

[0067] An oral preparation for improving anemia after gastrectomy:

[0068] Includes the following ingredients: 4 servings of Vitamin B 12 4 parts intrinsic factor, 30 parts chickpea protein, 10 parts type III collagen peptide, 5 parts pH adjuster, 5 parts antioxidant, 12 parts dispersant, 32 parts β-cyclodextrin and 90 mL acetate buffer.

[0069] The pH adjuster consists of 3.125 parts citric acid and 1.875 parts ferulic acid; the antioxidant consists of 2.5 parts grape seed extract and 2.5 parts EGCG; and the dispersant consists of 2.7 parts Morinda officinalis polysaccharide, 8.9 parts mannitol and 0.4 parts ferulic acid.

[0070] The preparation method is as follows:

[0071] S1: Intrinsic factor was mixed with chickpea protein and type III collagen peptides and swollen in acetate buffer at pH 2.8 at 50°C for 40 min to obtain a composite carrier;

[0072] S2: Vitamin B 12 Mixed with β-cyclodextrin, the mixture was mixed at 35°C for 2 hours to form a microsphere inclusion complex, which was then mixed with the composite carrier obtained in step S1 to obtain mixture 1;

[0073] S3: Mixture 1, pH adjuster (adjust pH to 1.5), antioxidant and dispersant are added in sequence, mixed, granulated and tableted.

[0074] Example 3

[0075] An oral preparation for improving anemia after gastrectomy:

[0076] Includes the following ingredients: 3 servings of Vitamin B 12 6 parts intrinsic factor, 40 parts chickpea protein, 5 parts type III collagen peptide, 12 parts pH adjuster, 1 part antioxidant, 20 parts dispersant, 27 parts β-cyclodextrin and 125 mL acetate buffer.

[0077] The pH adjuster consists of 9 parts malic acid and 3 parts ferulic acid; the antioxidant consists of 0.75 parts grape seed extract and 0.25 parts EGCG; and the dispersant consists of 4.7 parts Morinda officinalis polysaccharide, 14.0 parts mannitol and 1.3 parts ferulic acid.

[0078] The preparation method is as follows:

[0079] S1: Intrinsic factor was mixed with chickpea protein and type III collagen peptides and swollen in acetate buffer at pH 3.2 at 60°C for 20 min to obtain a composite carrier;

[0080] S2: Vitamin B 12 Mixed with β-cyclodextrin, the mixture was mixed at 40°C for 1.5 h to form a microsphere inclusion complex, which was then mixed with the composite carrier obtained in step S1 to obtain mixture 1;

[0081] S3: Mixture 1, pH adjuster (adjust pH to 2.5), antioxidant and dispersant are added in sequence, mixed, granulated and tableted.

[0082] Comparative Example 1

[0083] An oral formulation for improving anemia after gastrectomy, compared with Example 1, differs only in the amount of raw materials:

[0084] Includes the following ingredients: 5 servings of Vitamin B 12 7.5 parts intrinsic factor, 25 parts chickpea protein, 12 parts type III collagen peptide, 4 parts pH adjuster, 12.5 parts antioxidant, 10 parts dispersant, 50 parts β-cyclodextrin and 102 mL acetate buffer.

[0085] The pH adjuster consists of 2.5 parts malic acid and 1.5 parts ferulic acid; the antioxidant consists of 8.3 parts grape seed extract and 4.2 parts EGCG; and the dispersant consists of 2.35 parts Morinda officinalis polysaccharide, 7.06 parts mannitol and 0.59 parts ferulic acid.

[0086] The rest is the same as in Example 1.

[0087] Comparative Example 2

[0088] An oral formulation for improving anemia after gastrectomy, compared with Example 1, uses soy protein instead of chickpea protein and gallic acid instead of EGCG.

[0089] Includes the following ingredients: 2 servings of Vitamin B 12 3 parts intrinsic factor, 35 parts soy protein, 8 parts type III collagen peptides, 8 parts pH adjuster, 3 parts antioxidant, 17 parts dispersant, 20 parts β-cyclodextrin and 130 mL acetate buffer.

[0090] The pH adjuster consists of 5 parts malic acid and 3 parts ferulic acid; the antioxidant consists of 2 parts grape seed extract and 1 part gallic acid; and the dispersant consists of 4 parts Morinda officinalis polysaccharide, 12 parts mannitol and 1 part ferulic acid.

[0091] The preparation method is as follows:

[0092] S1: Intrinsic factor was mixed with soy protein and type III collagen peptides and swollen in acetate buffer at pH 3.0 at 55°C for 30 min to obtain a composite carrier;

[0093] S2: Vitamin B 12 Mixed with β-cyclodextrin, the mixture was mixed at 38°C for 2 hours to form a microsphere inclusion complex, which was then mixed with the composite carrier obtained in step S1 to obtain mixture 1;

[0094] S3: Mixture 1, pH adjuster (adjust pH to 2.0), antioxidant and dispersant are added in sequence, mixed, granulated and tableted.

[0095] Comparative Example 3

[0096] An oral preparation for improving anemia after gastrectomy.

[0097] Includes the following ingredients: 2 servings of Vitamin B 12 3 parts intrinsic factor, 43 parts type III collagen peptides, 8 parts pH adjuster, 3 parts antioxidant, 17 parts dispersant, 20 parts β-cyclodextrin and 130 mL acetate buffer.

[0098] The pH adjuster consists of 5 parts malic acid and 3 parts ferulic acid; the antioxidant consists of 2 parts grape seed extract and 1 part EGCG; and the dispersant is mannitol.

[0099] The preparation method is as follows:

[0100] S1: Intrinsic factor and type III collagen peptides were mixed and swollen in acetate buffer at pH 3.0 at 55°C for 30 min to obtain a composite carrier;

[0101] S2: Vitamin B 12Mixed with β-cyclodextrin, the mixture was mixed at 38°C for 2 hours to form a microsphere inclusion complex, which was then mixed with the composite carrier obtained in step S1 to obtain mixture 1;

[0102] S3: Mixture 1, pH adjuster (adjust pH to 2.0), antioxidant and dispersant are added in sequence, mixed, granulated and tableted.

[0103] Test Example 1

[0104] Vitamin B1 was determined using the paddle method (50 rpm) as defined in the Chinese Pharmacopoeia, simulating gastric juice (pH=1.2) and intestinal juice (pH=6.8) environments. 12 Release rate.

[0105] 1. Preparation of dissolution medium:

[0106] (1) Simulated gastric juice (pH=1-2): Take 16.4 mL of dilute hydrochloric acid (equivalent to 3.84 mL of hydrochloric acid), add water to 800 mL, add 10 g of pepsin, and make up to 1000 mL.

[0107] (2) Simulated intestinal fluid (pH=6-7): Dissolve 6.8 g of potassium dihydrogen phosphate in 500 mL of water, adjust the pH to 6.8 with 0.1 mol / L NaOH, add 10 g of pancreatic enzyme and bring the volume to 1000 mL.

[0108] 2. Instruments and parameters:

[0109] Dissolution apparatus: ZRS-8G intelligent dissolution tester (paddle method, 50 rpm).

[0110] Temperature control: 37℃±0.5℃ constant temperature water bath.

[0111] Sampling points: 5, 10, 15, 30, 45 minutes (6 samples at each time point).

[0112] 3. Testing

[0113] Determined by high performance liquid chromatography (Appendix VD, Part II, Chinese Pharmacopoeia 2005).

[0114] Instrument: Agilent 1100 high performance liquid chromatograph;

[0115] Column: Kromasil C18150 × 4.6 mm, 5 μm;

[0116] Chromatographic conditions and system suitability tests were conducted using octadecylsilane-bonded silica gel as the packing material.

[0117] The mobile phase was methanol-acetonitrile-triethylamine phosphate buffer (pH=7.0, 25:85:400); the detection wavelength was 267 nm; the theoretical plate number, calculated based on the methylcobalamin peak, should be no less than 2000.

[0118] Vitamin B 12 The release rate results are shown in Table 1.

[0119] Table 1. Vitamin B 12 Release rate

[0120]

[0121] As can be seen from the data in Table 1, compared with the comparative example, the oral formulation prepared in the embodiments of the present invention better meets the requirements of maintaining integrity in the gastric acid environment (pH=1-3) and sustained release in the intestine (pH=6-7).

[0122] Test Example 2

[0123] Examples 1-3 and Comparative Examples 1-3 of the present invention were subjected to accelerated testing at 40°C and 75% relative humidity for 6 months to detect impurity content and vitamin B. 12 The degradation rate is shown in Table 2.

[0124] Table 2. Stability Test Results

[0125]

[0126] As shown in Table 2, the oral formulation prepared in the embodiments of the present invention has significantly improved stability compared with the comparative example.

[0127] Test Example 3

[0128] Animal experiments on malnutrition-induced anemia:

[0129] (1) Experimental animals: 35 small pet dogs (breeds selected from Poodle, Chihuahua, Corgi and Shiba Inu), aged 12-18 months.

[0130] (2) Symptoms: Progressive emaciation and malnutrition occur. The body becomes weak and feeble, the abdomen curls up, the coat becomes rough, the visible mucous membranes become pale, and in the later stages, the body becomes extremely weak, swaying, and has difficulty standing up, until it becomes unable to stand up and the whole body fails.

[0131] (3) Grouping: The experimental animals were randomly divided into 7 groups, namely blank control group, Example 1-Example 3 group, and Comparative Example 1-Comparative Example 3 group, with 5 animals in each group.

[0132] (4) Criteria for evaluating therapeutic efficacy:

[0133] Apparent characteristics:

[0134] ① Ineffective: Pale oral and gingival mucosa, rough and dull coat, depressed mood, and loss of appetite;

[0135] ②Effective: Pink oral cavity and gum mucosa, smooth and shiny coat, good mental state, and normal appetite.

[0136] Functional indicators:

[0137] ① Ineffective: Low hemoglobin level (Hb, g / L), canine hemoglobin concentration <120;

[0138] ② Effective: Hemoglobin levels (Hb, g / L) are normal, and canine hemoglobin concentration is above 120. Between 180 and 180.

[0139] (5) Administration of medication:

[0140] Examples 1-3 and Comparative Examples 1-3 were each fed their prepared oral formulations at a dose of 1 g / kg, twice daily for 7 consecutive days.

[0141] The blank control group was fed physiological saline at a dose of 1 g / kg twice a day for 7 consecutive days.

[0142] (6) The results are shown in Table 3 below.

[0143] Table 3. Results

[0144]

[0145] As can be seen from the data in Table 3, the oral formulation prepared in the embodiments of the present invention has significantly improved efficacy compared with the comparative example.

[0146] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. An oral preparation for improving anemia after a gastrectomy operation, characterized by, According to the mass fraction, the following raw materials are included: 2-3 parts of vitamin B 12 , 3-6 parts of intrinsic factor, 30-40 parts of chickpea protein, 5-10 parts of type III collagen peptide, 5-12 parts of pH regulator, 1-5 parts of antioxidant, 12-20 parts of dispersing agent, 20-32 parts of β-cyclodextrin and 90-130 mL of acetic acid buffer; the mass ratio of the vitamin B 12 and intrinsic factor is 1:(1-2); the pH regulator is malic acid and ferulic acid with a mass ratio of (5-9):3; the antioxidant is grape seed extract and epigallocatechin gallate with a mass ratio of (0.75-2.5):(0.25-2.5); the dispersing agent is radix morindae officinalis polysaccharide, mannitol and ferulic acid with a mass ratio of (2.7-4.7):(8.9-14):(0.4-1.3). The amino acid sequence of the internal factor is shown as SEQ ID NO:

1.

2. The method for preparing the oral preparation according to claim 1, characterized in that, The following steps are included: S1: mixing the internal factor with chickpea protein and type III collagen peptide, swelling in acetic acid buffer for 20-40 min to obtain a composite carrier; S2: Vitamin B 12 After the inclusion, the complex carrier is mixed to obtain a mixture 1. S3: mixing mixture 1, a pH regulator, an antioxidant, and a dispersant to granulate; In step S2, the inclusion is as follows: vitamin B 12 Mix with 8-10 times mass of β-cyclodextrin, mix at 35-40°C for 1.5-2h to form microsphere inclusion compound.

3. The preparation method of claim 2, characterized in that, In step S1, the pH of the acetic acid buffer is 2.8-3.2; the swelling time is 20-30 min, and the temperature is 50-60°C; In step S3, the mixing is sequentially added in the following order: mixture 1, a pH regulator, an antioxidant, and a dispersant.

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