Composition formula of human umbilical cord blood-derived hematopoietic stem cells and application method thereof

Abstract

The invention relates to preparation engineering in the field of biotechnology, in particular to a composition formula of human umbilical cord blood-derived hematopoietic stem cells and an application method of the composition formula, and the human umbilical cord blood-derived hematopoietic stem cells are taken as a main material and are supplied to a human body in an oral manner to improve the gastrointestinal tract function. The composition comprises: 0-2 g per 45 ml of calcium carbonate; 0 to 20 mg of ferrous sulfate per 45 ml; 0.1 to 10 mg of zinc sulfate per 45 ml; and 0-3g of maltose is added to every 45ml. The application method is that the composition is orally taken, including direct oral taking, nasal feeding, gastric feeding and intestinal feeding. After the composition is orally taken, the gastrointestinal function is improved, the stomach pain is effectively relieved, and the gastric acid regurgitation frequency can be reduced to be close to zero.

Description

Technical Field

[0001] This invention relates to formulation engineering in the field of biotechnology, and in particular to a human-derived umbilical cord blood-derived formulation.

[0002] The composition and application method of hematopoietic stem cells, which are mainly derived from human umbilical cord blood, are administered orally to improve gastrointestinal function. Background Technology

[0003] The standards for stem cell sourcing, extraction, separation, purification, culture, storage, and transportation in this invention are as follows:

[0004] 1. International Standards:

[0005] FACT-NETCORD Standard: The gold standard for cord blood banks (CBB). Developed jointly by the Cell Therapy Certification Foundation and the International Cord Blood Bank Organization, it is used for cord blood collection, processing, testing, storage, distribution, and management.

[0006] AABB Standards: American Association of Blood Banks Standards.

[0007] Other national regulations: US FDA regulatory requirements (21 CFR Part 1271, etc.), EU ATMP (Advanced Therapeutic Products) Directive.

[0008] 2. Chinese Standards:

[0009] Technical Specifications for Umbilical Cord Blood Hematopoietic Stem Cell Banks

[0010] "Administrative Measures for Clinical Research on Stem Cells"

[0011] Regulations on the Management of Human Genetic Resources.

[0012] The Pharmacopoeia of the People's Republic of China.

[0013] Other regulations of local health commissions / health administration departments.

[0014] According to the above standards, the clinical application of cells is always via intravenous infusion or injection. Cells are not small molecules, nor are they true solutions; they possess biological activity. Direct entry into the user's circulatory and immune systems can trigger rejection reactions, affecting the effectiveness of the cells.

[0015] Hua Liu et al. pointed out [1] that, from an application perspective, conventional intravenous injection therapy based on live cells faces the risks of immune rejection and serious infection. Oral administration, on the other hand, is considered the preferred option due to its non-invasiveness, safety, convenience, and high patient compliance.

[0016] The authors further point out that the main reason for impaired cell viability is the susceptibility of cells to damage during isolation and transplantation. Furthermore, the lack of growth factors required for stem cell survival and function after injection, along with the abundance of damage-related molecular patterns such as reactive oxygen species (ROS) and inflammatory cytokines, collectively contributes to cell ineffectiveness. Meanwhile, stem cell-based therapies are mostly limited to local and intravenous injections. However, local inoculation is unsuitable for diffuse lesions such as multifocal ulcers in Crohn's disease, while the efficacy of systemic infusion is limited by low repositioning capacity. Moreover, due to the invasiveness of local and intravenous inoculation, the dosage and frequency of stem cell application are limited; therefore, developing oral stem cell-based therapies is crucial for advancing the treatment of gastrointestinal diseases. In the digestive tract, oral administration has a direct effect on the local mucosa, improving drug utilization in gastrointestinal cancers and inflammatory bowel disease. Furthermore, utilizing the intestinal immune microenvironment and gut microbiota, oral delivery strategies can provide alternative therapies for systemic immune diseases and microbiome-related diseases.

[0017] References:

[0018] [1] Hua Liu, Yanmiao Fan, Jie Zhong, et al., Advance in oral delivery of living material, Biomedical Technology, 3 (2023) 26–39 Summary of the Invention

[0019] The purpose of this invention is to overcome the deficiencies in the existing technology and provide a composition formulation and application method that is administered orally to the human body. After being absorbed through the digestive tract, it can reduce rejection reactions. Furthermore, after oral administration, this product directly contacts the gastrointestinal tract, clearly improving gastrointestinal function. Compared with intravenous infusion and injection, oral administration via cells reaches the gastrointestinal mucosa more directly.

[0020] The technical solutions of the present invention are as follows:

[0021] A compositional formulation of human umbilical cord blood-derived hematopoietic stem cells, said composition comprising:

[0022] Calcium carbonate, 0-2g per 45ml; ferrous sulfate, 0-20mg per 45ml; zinc sulfate, 0.1-10mg per 45ml; maltose, 0-3g per 45ml.

[0023] Furthermore, the calcium carbonate content is preferably 0.5~1.5g per 45ml.

[0024] Furthermore, the ferrous sulfate content is preferably 1-5 mg per 45 ml.

[0025] Furthermore, the zinc sulfate content is preferably 4-6 mg per 45 ml.

[0026] Furthermore, the maltose content is preferably 1-2g per 45ml.

[0027] A method for applying a composition formulation of human umbilical cord blood-derived hematopoietic stem cells, wherein the composition is administered orally to relieve stomach pain.

[0028] A method for applying a composition formulation of human umbilical cord blood-derived hematopoietic stem cells, wherein the composition is administered orally to reduce the frequency of acid reflux to near zero.

[0029] A method for applying a composition formulation of human umbilical cord blood-derived hematopoietic stem cells, wherein the composition is administered orally to improve colonic metabolic function and form stool.

[0030] A method for applying a composition formulation of human umbilical cord blood-derived hematopoietic stem cells, wherein the composition is administered orally to adjust the body mass index (BMI) and correct underweight conditions to normal.

[0031] The above application methods include oral administration, nasal feeding, gastric feeding, and enteral feeding.

[0032] The beneficial technical effects of this invention are as follows:

[0033] 1. Gastrointestinal function improved after oral administration of this composition.

[0034] 2. Oral application of this composition can effectively relieve stomach pain.

[0035] 3. Using this product can reduce the frequency of acid reflux to near zero.

[0036] 4. This product can improve the metabolic function of the large intestine and make the stool form.

[0037] 5. Using this product can adjust a person's body mass index (BMI) from underweight to a normal level. Attached Figure Description

[0038] Figure 1 This diagram illustrates the trend of body mass index (BMI) changes after taking this product, showing how BMI adjusts from slightly underweight to normal. The horizontal axis represents age, the vertical axis represents body mass index, and the shaded area represents the normal BMI value. Detailed Implementation

[0039] The implementation standards of this invention are as follows:

[0040] 1. International Standards:

[0041] FACT-NETCORD Standard: The gold standard for cord blood banks (CBB). Developed jointly by the Cell Therapy Certification Foundation and the International Cord Blood Bank Organization, it is used for cord blood collection, processing, testing, storage, distribution, and management.

[0042] AABB Standards: American Association of Blood Banks Standards.

[0043] Other national regulations: US FDA regulatory requirements (21 CFR Part 1271, etc.), EU ATMP (Advanced Therapeutic Products) Directive.

[0044] 2. Chinese Standards:

[0045] Technical Specifications for Umbilical Cord Blood Hematopoietic Stem Cell Banks

[0046] "Administrative Measures for Clinical Research on Stem Cells"

[0047] Regulations on the Management of Human Genetic Resources.

[0048] The Pharmacopoeia of the People's Republic of China.

[0049] Other regulations of local health commissions / health administration departments.

[0050] Based on the above standards, 10 billion hematopoietic stem cells were extracted, separated, purified, cultured, and proliferated from human umbilical cord blood and dispersed in a 45ml aqueous solution containing 0.5g calcium carbonate, 3mg ferrous sulfate, 5mg zinc sulfate, and 1g maltose.

[0051] This is a single-dose oral application, and transient reactions such as hiccups, fatigue, and drowsiness may occur. Within two weeks, acid reflux and stomach pain will subside, bowel function will improve, stools will become formed, stomach pain will gradually disappear after initial relief, cold hands and feet and lower abdominal coldness will be relieved, and there will be no recurrence in winter. BMI will adjust from slightly underweight to normal. Figure 1 As shown in Table 1, according to the "Guidelines for the Prevention and Control of Overweight and Obesity in Chinese Adults," the BMI reference standards are as follows:

[0052] Body fatness Underweight normal weight overweight obesity BMI value (kg / m²) <18.5 18.5-23.9 24.0-27.0 ≥28

[0053] Table 1. Relationship between obesity level and BMI

[0054] To demonstrate the safety of the formulation of the present invention, the summary report of the "Single-dose toxicity test of the live biological agent administered by gavage to SD rats" and the "Safety Assessment Report" of the composition of the present invention are provided as evidence, see the accompanying "Other Supporting Documents".

Claims

1. A compositional formulation of hematopoietic stem cells derived from human umbilical cord blood, characterized in that, The composition comprises: calcium carbonate, 0-2g per 45ml; ferrous sulfate, 0-20mg per 45ml; zinc sulfate, 0.1-10mg per 45ml; and maltose, 0-3g per 45ml.

2. The compositional formulation of human umbilical cord blood-derived hematopoietic stem cells according to claim 1, characterized in that: The calcium carbonate content is 0.5~1.5g per 45ml.

3. The compositional formulation of human umbilical cord blood-derived hematopoietic stem cells according to claim 1, characterized in that: The ferrous sulfate content is 1~5mg per 45ml.

4. The compositional formulation of human umbilical cord blood-derived hematopoietic stem cells according to claim 1, characterized in that: The zinc sulfate content is 4-6 mg per 45 ml.

5. The compositional formulation of human umbilical cord blood-derived hematopoietic stem cells according to claim 1, characterized in that: The maltose content is 1-2g per 45ml.

6. The method of applying the composition formulation of human umbilical cord blood-derived hematopoietic stem cells according to claim 1, characterized in that: The composition is administered orally to relieve stomach pain.

7. The method of applying the composition formulation of human umbilical cord blood-derived hematopoietic stem cells according to claim 1, characterized in that: When the composition is administered orally, it reduces the frequency of acid reflux to near zero.

8. The method of applying the composition formulation of human umbilical cord blood-derived hematopoietic stem cells according to claim 1, characterized in that: The composition is administered orally to improve colonic metabolic function and form stool.

9. The method of applying the composition formulation of human umbilical cord blood-derived hematopoietic stem cells according to claim 1, characterized in that: The composition is administered orally to adjust the body mass index (BMI) and correct underweight conditions to normal.

10. The application method according to any one of claims 6-9, characterized in that: The oral administration methods include direct oral administration, nasal feeding, gastric feeding, and enteral feeding.

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