Nutritional composition for assistant improvation of the conditions of patients with

Abstract

The invention discloses a nutritional composition for assisting in improving symptoms of a patient with propionemia and / or methylmalonemia. The invention provides a nutritional composition. The nutritional composition comprises plant fat powder and nucleotide components, wherein in the nutritional composition, in terms of weight, medium chain triglyceride (MCT) accounts for 20%-40% of the total fatty acids of the nutritional composition, and in addition, in terms of weight of the nutritional composition, the nutritional composition contains 0.01-0.15 part by weight of a nucleotide component. The nutritional composition can significantly reduce the generation of propionic acid and the accumulation of propionic acid abnormal metabolites, effectively controls the concentration of the propionic acid metabolite, and assists in improving the content of the propionic acid abnormal metabolites through the content of MCT and nucleotide, thereby improving the living quality of patients.

Description

Technical Field

[0001] This invention relates to a nutritional composition that helps improve symptoms in patients with propionic acidemia and / or methylmalonic acidemia, belonging to the food field. Background Technology

[0002] Propionic acidemia, also known as propionic aciduria, is caused by decreased or absent activity of propionyl-CoA carboxylase (PCC) in mitochondria. This leads to the accumulation of propionic acid and its byproducts in the body during the metabolism of branched-chain amino acids and odd-chain fatty acids, resulting in respiratory chain dysfunction and causing a series of biochemical abnormalities, nervous system damage, and other multi-system damage. It is an autosomal recessive genetic disorder. With the application of tandem mass spectrometry in newborn screening and clinical testing for inherited metabolic diseases, the prevalence has become clearer. Worldwide, it is estimated to be approximately 1 / 360,000 to 1 / 20,000, and in China, approximately 1 / 200,000. However, there are significant regional variations, ranging from 1 / 280,000 to 1 / 90,000. Propionic acidemia is a rare disease, but a common type of organic acidemia. Clinical manifestations are nonspecific and vary greatly from person to person. It can occur from infancy to adulthood, primarily leading to metabolic acidosis, hyperammonemia, encephalopathy, and cardiomyopathy, resulting in disability or death. Clinical identification is difficult, requiring analysis of urinary organic acids, blood acylcarnitine profiles, and genetic diagnosis. Early diagnosis and treatment with diet, medication, or liver transplantation can allow some patients to lead normal lives. Clinically, treatment primarily focuses on life support, including actively supplementing calories, promoting protein synthesis, inhibiting catabolism, and reducing the production of toxic metabolites such as propionic acid. Reference 1 used stable isotope technology to detect propionic acid levels in patients with propionic acidemia and methylmalonic acidemia. The results showed that although there are individual differences, approximately 50% of propionic acid comes from the metabolic breakdown of amino acids, 25% from the catabolism of odd-chain fatty acids, and the remainder from fermentation by intestinal flora.

[0003] The prior art provides some solutions, such as: Reference 2 attempts to provide a composition that can improve the propionic acid content in patients with propionic acidemia and methylmalonic acidemia. However, limiting the intake of methionine, threonine, valine and isoleucine does not solve the problem of propionic acid production in patients, and therefore there is still room for further improvement; while Reference 3 attempts to limit the propionic acid produced by the intestinal flora to alleviate symptoms.

[0004] It can be seen that although the methods proposed in the above literature have certain effects, they still have limitations.

[0005] References

[0006] References 1 LEONARD JV. Stable isotope studies in propionic and methylmalonic acidaemia[J]. European Journal of Pediatrics, 1997, 156: S67-S69.

[0007] Reference 2 CN107751997A

[0008] Reference 3 CN112805010A Summary of the Invention

[0009] The problem the invention aims to solve

[0010] Current nutritional compositions for patients with propionic acidemia, while regulating metabolic precursors by simply restricting the intake of specific amino acids (such as methionine and threonine), have not effectively blocked propionic acid produced by other metabolic pathways in the body; or they inhibit propionic acid from the gut microbiota, which has limited improvement on the accumulation of propionic acid produced by the body's own metabolism.

[0011] Therefore, there is an urgent need for a method that optimizes or synergistically improves propionic acid levels in patients with propionic acidemia by considering not only the ratio of amino acids but also the content of MCT and nucleotides in lipids. This method would be more suitable for the target population and would alleviate the discomfort symptoms caused by propionic acid, either directly or indirectly.

[0012] Solution for solving the problem

[0013] [1]. A nutritional composition comprising vegetable fat powder and nucleotide components;

[0014] In the nutritional composition, medium-chain triglycerides account for 20%-40% of the total fatty acids by weight.

[0015] Furthermore, based on the weight of the nutritional composition, the nutritional composition contains 0.01-0.15 parts by weight of nucleotide components.

[0016] [2]. The nutritional composition according to [1], wherein the nutritional composition contains 0.02-0.1 parts by weight of nucleotide components based on the weight of the nutritional composition.

[0017] [3]. The nutritional composition according to [1] or [2], wherein the nutritional composition contains 30-90 parts by weight of vegetable fat powder based on the weight of the nutritional composition.

[0018] [4]. The nutritional composition according to any one of [1]-[3], wherein the fat content of the vegetable fat powder is 30% to 60% by weight.

[0019] [5]. The nutritional composition according to any one of [1]-[4], wherein the nutritional composition further comprises amino acid components, docosahexaenoic acid oil powder, arachidonic acid oil powder, complex minerals and complex vitamins.

[0020] [6]. The nutritional composition according to [5], wherein the amino acid component comprises at least one of cystine, histidine, leucine, lysine, phenylalanine, tryptophan, tyrosine, aspartic acid, serine, glutamine, proline, glycine, alanine, and arginine.

[0021] [7]. The nutritional composition according to any one of [1]-[6], wherein the nutritional composition further comprises maltodextrin.

[0022] [8]. Use of the nutritional composition according to any one of [1]-[7] in the preparation of products that help improve propionic acidemia and / or methylmalonic acidemia.

[0023] [9]. According to the application described in [8], wherein the aid to improve propionic acidemia and / or methylmalonic acidemia includes: the discomfort caused to an individual by propionic acid and / or propionic acid metabolites;

[0024] Preferably, the aid to improve propionic acidemia and / or methylmalonic acidemia includes reducing the production of propionic acid metabolites and / or lowering the propionic acid content in the individual.

[0025]

[10] . According to the application described in [9], the individual is an infant, child or adult.

[0026] The effects of the invention

[0027] The product of this invention can significantly reduce propionic acid production and the accumulation of abnormal propionic acid metabolites, effectively control the concentration of propionic acid metabolite, and improve the content of abnormal propionic acid metabolites by optimizing the content of MCT and nucleotides in lipids, thereby improving the quality of life of patients. Detailed Implementation

[0028] Various exemplary embodiments, features, and aspects of the present invention will be described in detail below. The term "exemplary" as used herein means "serving as an example, embodiment, or illustration." Any embodiment described herein as "exemplary" is not necessarily to be construed as superior to or better than other embodiments.

[0029] Furthermore, to better illustrate the present invention, numerous specific details are set forth in the following detailed embodiments. Those skilled in the art should understand that the present invention can be practiced without certain specific details. In other instances, methods, means, apparatus, and steps well known to those skilled in the art have not been described in detail in order to highlight the spirit of the present invention.

[0030] Unless otherwise stated, all units used in this specification are international standard units, and all numerical values ​​and ranges appearing in this invention should be understood to include systematic errors that are unavoidable in industrial production.

[0031] In this specification, the word "may" has two meanings: to perform a certain process and not to perform a certain process.

[0032] In this specification, references to "some specific / preferred embodiments," "other specific / preferred embodiments," "implementation," etc., refer to specific elements (e.g., features, structures, properties, and / or characteristics) related to that embodiment, which are included in at least one of the embodiments described herein and may or may not be present in other embodiments. Furthermore, it should be understood that these elements may be combined in any suitable manner in various embodiments.

[0033] In this specification, the range of values ​​referred to as "value A to value B" refers to the range including the endpoint values ​​A and B.

[0034] In this invention, the term "infant" is used to refer to the human group aged 0 to 6 months.

[0035] In this invention, the term "older infant" refers to the human group aged 6 to 12 months.

[0036] In this invention, the term "infant" is used to refer to the human group aged 12 to 36 months.

[0037] In this invention, the term "infant" refers to the human group under the age of 3.

[0038] In this invention, the terms "comprising," "having," "including," or "containing" can mean included or open-ended, and do not exclude additional, uncited components or method steps. At the same time, "comprising," "having," "including," or "containing" can also mean closed-ended, excluding additional, uncited components or method steps.

[0039] (Nutritional composition)

[0040] A nutritional composition comprising vegetable fat powder and nucleotide components; wherein, by weight, medium-chain triglycerides account for 20%-40% of the total fatty acids in the nutritional composition, and by weight, the nutritional composition contains 0.01-0.15 parts by weight of nucleotide components.

[0041] Nucleotide components

[0042] In some embodiments, the nutritional composition contains 0.01-0.15 parts by weight of nucleotide components.

[0043] In some preferred embodiments, the nutritional composition contains 0.02-0.1 parts by weight of nucleotide components, such as 0.02 parts by weight, 0.03 parts by weight, 0.04 parts by weight, 0.05 parts by weight, 0.06 parts by weight, 0.07 parts by weight, 0.08 parts by weight, 0.09 parts by weight, 0.1 parts by weight, etc.

[0044] In some more preferred embodiments, the nutritional composition contains 0.04-0.08 parts by weight of nucleotide components, such as 0.05 parts by weight, 0.06 parts by weight, 0.07 parts by weight, etc., based on the weight of the nutritional composition.

[0045] In some embodiments, the nucleotide component includes at least one of 5'-cytosine nucleotide (CMP), 5'-cytosine nucleotide (UMP), 5'-adenine nucleotide (AMP), 5'-guanine nucleotide (GMP), and 5'-hypoxanthine nucleotide (IMP).

[0046] In some embodiments, the nucleotide component may be provided by a compound containing the corresponding component. In some exemplary embodiments, the nucleotide component includes: 5'-cytidine monophosphate (5'-CMP), 5'-uridine monophosphate (5'-UMP), 5'-adenosine monophosphate (5'-AMP), disodium 5'-cytidine sulfate, disodium 5'-uridine sulfate, 5'-adenosine, disodium 5'-guanylate, and disodium 5'-inosine sulfate.

[0047] Nucleotide components can be commercially obtained by those skilled in the art, such as various commercially available compound nucleotides, such as nucleotides produced by Dalian Zhenao Biotechnology Co., Ltd., but not limited thereto.

[0048] medium-chain triglycerides

[0049] In some embodiments, the medium-chain triglycerides, by weight, account for 20% to 40% of the total fatty acids in the nutritional composition, for example, 20%, 25%, 30%, 35%, or 40%.

[0050] In some preferred embodiments, the medium-chain triglycerides account for 30-40% of the total fatty acids in the nutritional composition by weight.

[0051] In this specification, medium-chain triglycerides (MCTs) refer to triglycerides formed by the esterification of saturated fatty acids (i.e., medium-chain fatty acids (MCFAs)) with 6 to 12 carbon atoms and glycerol.

[0052] Plant fat powder

[0053] In some embodiments, the nutritional composition contains 30-90 parts by weight of vegetable fat powder.

[0054] In some embodiments, the nutritional composition contains 40-80 parts by weight of vegetable fat powder.

[0055] In some preferred embodiments, the nutritional composition contains 45-70 parts by weight of vegetable fat powder.

[0056] In some exemplary embodiments, the nutritional composition contains, by weight, 50-65 parts of vegetable fat powder, such as 50 parts, 51 parts, 53 parts, 55 parts, 58 parts, 60 parts, 62 parts, 65 parts, etc.

[0057] In some embodiments, the fat content of the vegetable fat powder is 30% to 60%, preferably 40% to 50%. In some exemplary embodiments, vegetable fat powder can be commercially available or prepared by conventional methods by those skilled in the art. Vegetable fat powder typically contains wall materials (e.g., maltodextrin, solid corn syrup), 1,3-dioleoyl-2-palmitoyl glycerol (OPO), vegetable oil, emulsifiers (e.g., mono- and diglycerides of fatty acids and citric acid fatty acid glycerides), and antioxidants (e.g., mixed tocopherol concentrate and sodium ascorbate palmitate). For example, vegetable fat powder can be purchased from Jiawei Green Biotechnology (Heilongjiang) Co., Ltd., but is not limited thereto.

[0058] For example, the specific components of the vegetable fat powder are as follows: the fat content is 40% to 50% by weight, maltodextrin and solid corn syrup provide carbohydrates as wall materials, accounting for 50% to 70% by weight, 0.5% to 5% by weight of mono- and diglycerides of fatty acids and citric acid fatty acid glycerides are added as emulsifiers, and 0.1% to 1% by weight of mixed tocopherol concentrate and sodium ascorbate palmitate are added as antioxidants.

[0059] Other ingredients

[0060] In some embodiments, the nutritional composition further includes amino acid components, docosahexaenoic acid (DHA) oil powder, arachidonic acid (RAA) oil powder, complex minerals, and complex vitamins.

[0061] (Amino acid composition)

[0062] In some embodiments, the amino acid component includes at least one selected from cystine, histidine, leucine, lysine, phenylalanine, tryptophan, tyrosine, aspartic acid, serine, glutamine, proline, glycine, alanine, and arginine.

[0063] In some preferred embodiments, the amino acid composition includes cysteine, histidine, leucine, lysine, phenylalanine, tryptophan, tyrosine, aspartic acid, serine, glutamine, proline, glycine, alanine, and arginine. In some embodiments, the nutritional composition does not contain methionine, threonine, valine, and isoleucine.

[0064] In some embodiments, the nutritional composition contains 10-50 parts by weight of amino acids.

[0065] In some preferred embodiments, the nutritional composition contains 10-30 parts by weight of amino acids.

[0066] In some exemplary embodiments, the nutritional composition contains 15-25 parts by weight of amino acids, such as 16, 17, 18, 19, 20, 21, 22, 23, etc.

[0067] In some specific embodiments, the amino acid composition comprises 3-6% by weight cystine, 2-6% by weight histidine, 7-15% by weight leucine, 5-12% by weight lysine, 3-9% by weight phenylalanine, 0.5-4.5% by weight tryptophan, 1.5-8% by weight tyrosine, 4.5-12.3% by weight aspartic acid, 3-9.5% by weight serine, 12.5-25.5% by weight glutamine, 7-14% by weight proline, 1-5% by weight glycine, 3.5-6.5% by weight alanine, and 2.5-7.5% by weight arginine.

[0068] (docosahexaenoic acid and arachidonic acid)

[0069] In some embodiments, the nutritional composition contains docosahexaenoic acid (DHA) and arachidonic acid (ARA).

[0070] In some exemplary embodiments, the docosahexaenoic acid (DHA) is provided by docosahexaenoic acid oil powder.

[0071] In some exemplary embodiments, arachidonic acid (ARA) is provided by arachidonic acid oil powder.

[0072] In some embodiments, the docosahexaenoic acid (DHA) of the present invention comprises 0.5-10 parts by weight of the nutritional composition of the present invention.

[0073] In some preferred embodiments, the docosahexaenoic acid (DHA) component of the present invention comprises 1-6 parts by weight of the nutritional composition.

[0074] In some exemplary embodiments, the docosahexaenoic acid (DHA) of the present invention comprises, by weight, 2-5 parts of the nutritional composition of the present invention, for example, 2 parts of weight, 3 parts of weight, 4 parts of weight, 5 parts of weight, etc.

[0075] In some exemplary embodiments, the docosahexaenoic acid (DHA) of the present invention comprises 1-2 parts by weight of the nutritional composition of the present invention.

[0076] In some embodiments, the arachidonic acid (ARA) of the present invention comprises 0.5-10 parts by weight of the nutritional composition.

[0077] In some preferred embodiments, the arachidonic acid (ARA) component of the present invention comprises 1-6 parts by weight of the nutritional composition.

[0078] In some exemplary embodiments, the arachidonic acid (ARA) of the present invention comprises 2-5 parts by weight, for example 2 parts by weight, 3 parts by weight, 4 parts by weight, 5 parts by weight, etc., in the nutritional composition.

[0079] In some exemplary embodiments, the arachidonic acid (ARA) of the present invention comprises 1-2 parts by weight of the nutritional composition of the present invention.

[0080] Docosahexaenoic acid (DHA) oil powder and arachidonic acid (RAA) oil powder are commercially available to those skilled in the art, such as those produced by JABY Biotech (Wuhan) Co., Ltd., but not limited to these.

[0081] (Composition of multivitamins)

[0082] In some embodiments, the nutritional composition also includes a multivitamin component.

[0083] In some specific embodiments, the multivitamin component in the nutritional composition includes vitamin A, vitamin D, vitamin E, vitamin K1, vitamin B1, vitamin B2, vitamin B6, and vitamin B1. 12 It contains at least one of the following: niacin, folic acid, pantothenic acid, vitamin C, biotin, and choline.

[0084] In some embodiments, the compound vitamin component of the present invention accounts for 0.1-1 parts by weight of the nutritional composition of the present invention.

[0085] In some preferred embodiments, the multivitamin component of the present invention comprises 0.2-0.8 parts by weight of the nutritional composition.

[0086] In some exemplary embodiments, the compound vitamin component of the present invention accounts for 0.3-0.6 parts by weight of the nutritional composition, for example, 0.3 parts by weight, 0.4 parts by weight, 0.5 parts by weight, 0.6 parts by weight, etc.

[0087] (Complex mineral components)

[0088] For the composite mineral components of the present invention, these composite mineral components are provided by compounds containing the corresponding elements.

[0089] Examples of compound mineral components include at least one of the following: sodium citrate, potassium chloride, copper sulfate, magnesium sulfate, ferric pyrophosphate, zinc sulfate, manganese sulfate, calcium citrate, calcium hydrogen phosphate, potassium iodate, and sodium selenite.

[0090] In some embodiments, the composite mineral components of the present invention include iron, magnesium, zinc, selenium, copper, manganese, calcium, phosphorus, sodium, potassium, chlorine, iodine, etc.

[0091] In some alternative embodiments, the nutritional composition may also contain at least one of other functional mineral elements, such as chromium, molybdenum, etc.

[0092] In some embodiments, the compound mineral component of the present invention comprises 1-10 parts by weight of the nutritional composition of the present invention.

[0093] In some preferred embodiments, the compound mineral component of the present invention accounts for 2-8 parts by weight of the nutritional composition of the present invention.

[0094] In some exemplary embodiments, the compound mineral component of the present invention accounts for 3-6 parts by weight of the nutritional composition, for example, 3 parts by weight, 4 parts by weight, 5 parts by weight, 6 parts by weight, etc.

[0095] The combination of the nutritional composition described in this invention with the above-mentioned ingredients helps to reduce the production of propionic acid metabolites.

[0096] These are commercially available to those skilled in the art, such as multivitamins and multiminerals produced by DSM-Firmay, but not limited to these.

[0097] (maltodextrin)

[0098] In some embodiments, the nutritional composition further comprises maltodextrin.

[0099] In some embodiments, the maltodextrin component of the present invention accounts for 2-25 parts by weight of the nutritional composition of the present invention.

[0100] In some preferred embodiments, the maltodextrin component of the present invention comprises 3-20 parts by weight of the nutritional composition.

[0101] In some exemplary embodiments, the maltodextrin component of the present invention accounts for 4-15 parts by weight of the nutritional composition, for example, 4 parts by weight, 5 parts by weight, 6 parts by weight, 8 parts by weight, 9 parts by weight, 10 parts by weight, 12 parts by weight, 15 parts by weight, etc.

[0102] The maltodextrin in the nutritional composition of the present invention, together with the glucose syrup and maltodextrin in the vegetable fat powder, serves as a source of carbohydrates.

[0103] In some exemplary embodiments, the nutrient comprising the composition includes any one of (1) to (7):

[0104] (1) 60 parts by weight of vegetable fat powder, 20 parts by weight of compound amino acids, 10 parts by weight of maltodextrin, 2.0 parts by weight of docosahexaenoic acid oil powder, 2.0 parts by weight of arachidonic acid oil powder, 5 parts by weight of compound minerals, 0.5 parts by weight of compound vitamins, and 0.06 parts by weight of compound nucleotides, of which MCT accounts for 20% of the total fatty acid content in the formula powder;

[0105] (2) 60 parts by weight of vegetable fat powder, 18 parts by weight of compound amino acids, 15 parts by weight of maltodextrin, 1.0 part by weight of docosahexaenoic acid oil powder, 1.0 part by weight of arachidonic acid oil powder, 3 parts by weight of compound minerals, 0.3 parts by weight of compound vitamins, and 0.1 parts by weight of compound nucleotides, of which MCT accounts for 20% of the total fatty acid content in the formula powder;

[0106] (3) 55 parts by weight of vegetable fat powder, 20 parts by weight of compound amino acids, 15 parts by weight of maltodextrin, 2.0 parts by weight of docosahexaenoic acid oil powder, 2.0 parts by weight of arachidonic acid oil powder, 4 parts by weight of compound minerals, 0.4 parts by weight of compound vitamins, and 0.1 parts by weight of compound nucleotides, of which MCT accounts for 30% of the total fatty acid content in the formula powder;

[0107] (4) 55 parts by weight of vegetable fat powder, 22 parts by weight of compound amino acids, 15 parts by weight of maltodextrin, 1.0 part by weight of docosahexaenoic acid oil powder, 1.0 part by weight of arachidonic acid oil powder, 5 parts by weight of compound minerals, 0.5 parts by weight of compound vitamins, and 0.05 parts by weight of compound nucleotides, of which MCT accounts for 40% of the total fatty acid content in the formula powder;

[0108] (5) 55 parts by weight of vegetable fat powder, 22 parts by weight of compound amino acids, 15 parts by weight of maltodextrin, 1.0 part by weight of docosahexaenoic acid oil powder, 1.0 part by weight of arachidonic acid oil powder, 5 parts by weight of compound minerals, 0.5 parts by weight of compound vitamins, and 0.1 parts by weight of compound nucleotides, of which MCT accounts for 40% of the total fatty acid content in the formula powder;

[0109] (6) 55 parts by weight of vegetable fat powder, 22 parts by weight of compound amino acids, 15 parts by weight of maltodextrin, 1.0 part by weight of docosahexaenoic acid oil powder, 1.0 part by weight of arachidonic acid oil powder, 5 parts by weight of compound minerals, 0.3 parts by weight of compound vitamins, and 0.02 parts by weight of compound nucleotides, of which MCT accounts for 40% of the total fatty acid content in the formula powder;

[0110] (7) 60 parts by weight of vegetable fat powder, 20 parts by weight of compound amino acids, 10 parts by weight of maltodextrin, 1.5 parts by weight of docosahexaenoic acid oil powder, 1.5 parts by weight of arachidonic acid oil powder, 5 parts by weight of compound minerals, 0.5 parts by weight of compound vitamins, and 0.03 parts by weight of compound nucleotides, of which MCT accounts for 20% of the total fatty acid content in the formula powder.

[0111] In some preferred embodiments, the nutrient comprising the composition includes any one of the following:

[0112] (1) 60 parts by weight of vegetable fat powder, 20 parts by weight of compound amino acids, 10 parts by weight of maltodextrin, 2.0 parts by weight of docosahexaenoic acid oil powder, 2.0 parts by weight of arachidonic acid oil powder, 5 parts by weight of compound minerals, 0.5 parts by weight of compound vitamins, and 0.06 parts by weight of compound nucleotides, of which MCT accounts for 20% of the total fatty acid content in the formula powder;

[0113] (3) 55 parts by weight of vegetable fat powder, 20 parts by weight of compound amino acids, 15 parts by weight of maltodextrin, 2.0 parts by weight of docosahexaenoic acid oil powder, 2.0 parts by weight of arachidonic acid oil powder, 4 parts by weight of compound minerals, 0.4 parts by weight of compound vitamins, and 0.1 parts by weight of compound nucleotides, of which MCT accounts for 30% of the total fatty acid content in the formula powder;

[0114] (4) 55 parts by weight of vegetable fat powder, 22 parts by weight of compound amino acids, 15 parts by weight of maltodextrin, 1.0 part by weight of docosahexaenoic acid oil powder, 1.0 part by weight of arachidonic acid oil powder, 5 parts by weight of compound minerals, 0.5 parts by weight of compound vitamins, and 0.05 parts by weight of compound nucleotides, of which MCT accounts for 40% of the total fatty acid content in the formula powder;

[0115] (5) 55 parts by weight of vegetable fat powder, 22 parts by weight of compound amino acids, 15 parts by weight of maltodextrin, 1.0 part by weight of docosahexaenoic acid oil powder, 1.0 part by weight of arachidonic acid oil powder, 5 parts by weight of compound minerals, 0.5 parts by weight of compound vitamins, and 0.1 parts by weight of compound nucleotides, of which MCT accounts for 40% of the total fatty acid content in the formula powder.

[0116] In some preferred embodiments, the nutritional composition includes: 55 parts by weight of vegetable fat powder, 22 parts by weight of compound amino acids, 15 parts by weight of maltodextrin, 1.0 part by weight of docosahexaenoic acid (DHA) oil powder, 1.0 part by weight of arachidonic acid (RAA) oil powder, 5 parts by weight of compound minerals, 0.5 parts by weight of compound vitamins, and 0.05 parts by weight of compound nucleotides, wherein MCT accounts for 40% of the total fatty acid content in the formula powder.

[0117] (use)

[0118] The present invention also provides the use of the above-described nutritional composition in the preparation of products that help improve propionic acidemia and / or methylmalonic acidemia.

[0119] In some implementations, the aid to improve propionic acidemia and / or methylmalonic acidemia includes: the discomfort caused to an individual by propionic acid and / or propionic acid metabolites.

[0120] In some preferred embodiments, the aid to improve propionic acidemia and / or methylmalonic acidemia includes reducing the production of propionic acid metabolites and / or lowering the propionic acid content in the individual.

[0121] In some implementations, the individual is an infant, a child, or an adult.

[0122] In some implementations, the individual suffers from propionic acidemia and / or methylmalonic acidemia.

[0123] It is understood that the specific amounts of each ingredient in the nutritional compositions of this invention, such as infant formula or children's formula, should be adjusted and determined to meet the requirements of the formula product indicators. In the infant formula or children's formula of this invention, product performance indicators not detailed or listed shall be implemented in accordance with the provisions of national standards and relevant standards and regulations for infant formula or children's formula.

[0124] The infant formula or children's formula of this invention uses commercially available ingredients, and the selection of each ingredient should meet relevant standards. Furthermore, the compound nutrients can also be formulated in-house. The term "compound" is used in this invention for ease of description and does not imply that the components in the compound must be mixed together before application. All ingredients should be added and used in accordance with relevant regulations.

[0125] It should be noted that, in infant formula of the present invention, the specific dosage of each ingredient should be adjusted and determined to meet the product index requirements of the formula. For the nutritional composition of the present invention used in infant formula, product performance indicators not detailed or listed should be implemented in accordance with the provisions of GB 25596-2025 Special Medical Purpose Infant Formula and GB 14880-2012 Standard for the Use of Food Fortifiers, as well as relevant standards and regulations.

[0126] (Preparation method)

[0127] The present invention also provides a method for preparing the above-mentioned nutritional composition.

[0128] In some specific embodiments, docosahexaenoic acid oil powder, arachidonic acid oil powder, compound vitamins, and compound nucleotides are premixed, and then the premixed material is mixed with the remaining materials mentioned above.

[0129] Reference examples, comparative examples, and embodiments

[0130] The embodiments of the present invention will be described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are for illustrative purposes only and should not be considered as limiting the scope of the invention. Unless otherwise specified in the examples, conventional conditions or conditions recommended by the manufacturer are followed. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0131] 1. Raw materials used in the reference examples, comparative examples, or embodiments:

[0132] Vegetable fat powder: Produced by Jiawei Green Biotechnology (Heilongjiang) Co., Ltd., model VPGE series. Besides the wall material, the powder contains OPO and other vegetable oils, emulsifiers, antioxidants, and may or may not contain MCT. The specific composition of the vegetable fat powder is as follows: by weight, the fat content is 40%~50% (of which MCT accounts for 0~55% of the total fatty acid content, and OPO accounts for 15%~30% of the total fatty acid content); maltodextrin and solid corn syrup provide carbohydrates as wall materials, accounting for 50%~7%; 0.5%~5% of mono- and diglycerides of fatty acids and citric acid fatty acid glycerides are added as emulsifiers; and 0.1%~1% of mixed tocopherol concentrate and sodium ascorbate palmitate are added as antioxidants.

[0133] Complex amino acids: In accordance with regulations, guidelines, and consensus requirements (excluding isoleucine, valine, threonine, and methionine), the composition of other amino acids, especially essential amino acids, meets the requirements for high-quality protein composition, with specific proportions as follows:

[0134]

[0135] Complex Minerals: DSM-Finmi Nutrition (Shanghai) Co., Ltd.;

[0136] Multivitamins: DSM-Finni Nutrition (Shanghai) Co., Ltd.;

[0137] Complex nucleotides: Dalian Zhenao Biotechnology Co., Ltd., Model I;

[0138] Docosahexaenoic acid (DHA) oil powder: Jiabiyou Biotechnology (Wuhan) Co., Ltd., model M3;

[0139] Arachidonic acid oil powder: Jiabiyou Biotechnology (Wuhan) Co., Ltd., model M3;

[0140] Maltodextrin: Baolingbao Biotechnology Co., Ltd., model MD20.

[0141] 2. Specific component ratios of the compositions (formula powder) in the reference examples, comparative examples, or embodiments:

[0142] Example 1: 65 parts by weight of vegetable fat powder, 18 parts by weight of compound amino acids, 5 parts by weight of maltodextrin, 2.0 parts by weight of docosahexaenoic acid oil powder, 2.0 parts by weight of arachidonic acid oil powder, 5 parts by weight of compound minerals, 0.5 parts by weight of compound vitamins, and 0 parts by weight of compound nucleotides; MCT accounts for 0% of the total fatty acid content in the formula powder.

[0143] Comparative Example 1: 60 parts by weight of vegetable fat powder, 20 parts by weight of compound amino acids, 10 parts by weight of maltodextrin, 1.0 part by weight of docosahexaenoic acid oil powder, 1.0 part by weight of arachidonic acid oil powder, 4 parts by weight of compound minerals, 0.4 parts by weight of compound vitamins, and 0.01 parts by weight of compound nucleotides; MCT accounted for 5% of the total fatty acid content in the formula powder.

[0144] Comparative Example 2: 65 parts by weight of vegetable fat powder, 18 parts by weight of compound amino acids, 6 parts by weight of maltodextrin, 2.0 parts by weight of docosahexaenoic acid oil powder, 2.0 parts by weight of arachidonic acid oil powder, 5 parts by weight of compound minerals, 0.5 parts by weight of compound vitamins, and 0.1 parts by weight of compound nucleotides; MCT accounted for 10% of the total fatty acid content in the formula powder.

[0145] Comparative Example 3: 58 parts by weight of vegetable fat powder, 30 parts by weight of compound amino acids, 2 parts by weight of maltodextrin, 1.5 parts by weight of docosahexaenoic acid oil powder, 1.5 parts by weight of arachidonic acid oil powder, 4 parts by weight of compound minerals, 0.4 parts by weight of compound vitamins, and 0.1 parts by weight of compound nucleotides; MCT accounted for 15% of the total fatty acid content in the formula powder.

[0146] Comparative Example 4: 60 parts by weight of vegetable fat powder, 20 parts by weight of compound amino acids, 10 parts by weight of maltodextrin, 1.0 part by weight of docosahexaenoic acid oil powder, 1.0 part by weight of arachidonic acid oil powder, 5 parts by weight of compound minerals, 0.5 parts by weight of compound vitamins, and 0 parts by weight of compound nucleotides; MCT accounted for 20% of the total fatty acid content in the formula powder.

[0147] Comparative Example 5: 60 parts by weight of vegetable fat powder, 20 parts by weight of compound amino acids, 10 parts by weight of maltodextrin, 1.0 part by weight of docosahexaenoic acid oil powder, 1.0 part by weight of arachidonic acid oil powder, 5 parts by weight of compound minerals, 0.5 parts by weight of compound vitamins, and 0 parts by weight of compound nucleotides; MCT accounted for 40% of the total fatty acid content in the formula powder.

[0148] Comparative Example 6: 58 parts by weight of vegetable fat powder, 22 parts by weight of compound amino acids, 10 parts by weight of maltodextrin, 1.5 parts by weight of docosahexaenoic acid oil powder, 1.5 parts by weight of arachidonic acid oil powder, 4 parts by weight of compound minerals, 0.5 parts by weight of compound vitamins, and 0.1 parts by weight of compound nucleotides; MCT accounted for 50% of the total fatty acid content in the formula powder.

[0149] Example 1: 60 parts by weight of vegetable fat powder, 20 parts by weight of compound amino acids, 10 parts by weight of maltodextrin, 2.0 parts by weight of docosahexaenoic acid oil powder, 2.0 parts by weight of arachidonic acid oil powder, 5 parts by weight of compound minerals, 0.5 parts by weight of compound vitamins, and 0.06 parts by weight of compound nucleotides; MCT accounts for 20% of the total fatty acid content in the formula powder.

[0150] Example 2: 60 parts by weight of vegetable fat powder, 18 parts by weight of compound amino acids, 15 parts by weight of maltodextrin, 1.0 part by weight of docosahexaenoic acid oil powder, 1.0 part by weight of arachidonic acid oil powder, 3 parts by weight of compound minerals, 0.3 parts by weight of compound vitamins, and 0.1 parts by weight of compound nucleotides; MCT accounts for 20% of the total fatty acid content in the formula powder.

[0151] Example 3: 55 parts by weight of vegetable fat powder, 20 parts by weight of compound amino acids, 15 parts by weight of maltodextrin, 2.0 parts by weight of docosahexaenoic acid oil powder, 2.0 parts by weight of arachidonic acid oil powder, 4 parts by weight of compound minerals, 0.4 parts by weight of compound vitamins, and 0.1 parts by weight of compound nucleotides; MCT accounts for 30% of the total fatty acid content in the formula powder.

[0152] Example 4: 55 parts by weight of vegetable fat powder, 22 parts by weight of compound amino acids, 15 parts by weight of maltodextrin, 1.0 part by weight of docosahexaenoic acid oil powder, 1.0 part by weight of arachidonic acid oil powder, 5 parts by weight of compound minerals, 0.5 parts by weight of compound vitamins, and 0.05 parts by weight of compound nucleotides; MCT accounts for 40% of the total fatty acid content in the formula powder.

[0153] Example 5: 55 parts by weight of vegetable fat powder, 22 parts by weight of compound amino acids, 15 parts by weight of maltodextrin, 1.0 part by weight of docosahexaenoic acid oil powder, 1.0 part by weight of arachidonic acid oil powder, 5 parts by weight of compound minerals, 0.5 parts by weight of compound vitamins, and 0.1 parts by weight of compound nucleotides; MCT accounts for 40% of the total fatty acid content in the formula powder.

[0154] Example 6: 55 parts by weight of vegetable fat powder, 22 parts by weight of compound amino acids, 15 parts by weight of maltodextrin, 1.0 part by weight of docosahexaenoic acid oil powder, 1.0 part by weight of arachidonic acid oil powder, 5 parts by weight of compound minerals, 0.3 parts by weight of compound vitamins, and 0.02 parts by weight of compound nucleotides; MCT accounts for 40% of the total fatty acid content in the formula powder.

[0155] Example 7: 60 parts by weight of vegetable fat powder, 20 parts by weight of compound amino acids, 10 parts by weight of maltodextrin, 1.5 parts by weight of docosahexaenoic acid oil powder, 1.5 parts by weight of arachidonic acid oil powder, 5 parts by weight of compound minerals, 0.5 parts by weight of compound vitamins, and 0.03 parts by weight of compound nucleotides; MCT accounts for 20% of the total fatty acid content in the formula powder.

[0156] The MCT percentage mentioned above is calculated by dividing the theoretical feed amount by the total fatty acids. The total fatty acids and individual fatty acids are tested according to the national standard method GB 5009.168.

[0157] Table 1. Formulations of Reference Examples, Comparative Examples, and Sample Examples

[0158]

[0159] 3. Production process of the composition (formula powder) in the reference examples, comparative examples, or embodiments:

[0160] Docosahexaenoic acid (DHA) oil powder, arachidonic acid (RAA) oil powder, compound vitamins, and compound nucleotides are premixed for 10 minutes at 15 rpm using a small bin mixer. The premixed materials are then mixed with the remaining materials using a large bin mixer at 25 rpm for 20 minutes. The mixture is then bottled to form the final product.

[0161] Test case

[0162] An in vitro fermentation test was conducted on the formula powder obtained from the above experiment:

[0163] The fermentation model was adjusted based on Sergio's research (Reference: PÉREZ-BURILLO S, MOLINO S, NAVAJAS-PORRAS B, et al. An in vitro batch fermentation protocol for studying the contribution of food to gut microbiota composition and functionality[J].Nature Protocols, 2021, 16(7): 3186-3209.). Fecal samples from patients with propionic acidemia (derived from 0-3 year old children with propionic acidemia, 3 males and 3 females, mixed and stored under anaerobic conditions) were diluted and inoculated (at a 10% volume ratio) onto in vitro fermentation broth medium. The medium was then placed in an anaerobic incubator (80% N2, 10% CO2, 10% H2), with the inoculated medium kept under slow shaking (5 rpm). After 24 hours, the fermentation broth was centrifuged at 10000 rpm at low temperature (0-4℃) for 10 min, and the supernatant was collected. The propionic acid content was determined by gas chromatography. Experimental data are expressed as mean ± standard deviation (mean ± SD). Each experiment was independently repeated at least three times. SPSS 16.0 software was used for statistical analysis of the experimental data, employing one-way ANOVA (Duncan's multiple range test). The results are shown in Table 2 below.

[0164] Table 2 Propionic acid content in the supernatant of fermentation broth

[0165]

[0166] Note: # indicates a comparison with the blank control group, p < 0.05.

[0167] Animal experiments were conducted on the formula powder obtained from the above experiments:

[0168] Seventy newborn 6-day-old Wistar rats were selected. The rats were randomly divided into 14 groups. From day 5 to day 28 after birth, the rats were subcutaneously injected twice a day (8 hours apart) with propionic acid solution (propionic acid dissolved in physiological saline, and the pH was adjusted to 7.2 with 5 mmol / L NaOH). The dose of propionic acid solution injected into rats was 8 μL / g body weight (approximately 8 mg / g); the injection concentration was based on the study by Brusque (reference: Brusque AM, Mello CF, Buchanan DN, et al. Effect of chemically induced propionic acidemia on neurobehavioral development of rats[J]. Pharmacology Biochemistry & Behavior, 1999, 64(3):529-34.): 0.72 μmol / g (approximately 53 μg / g) was administered from day 6 to 12 after birth; 1.68 μmol / g (approximately 124 μg / g) was administered from day 13 to 19 after birth; and 1.92 μmol / g (approximately 142 μg / g) was administered from day 20 to 28 after birth. The control group was injected with the same dose of physiological saline at 8 μL / g body weight (approximately 8 mg / g). Two weeks after birth, the young rats were weaned and randomly divided into 14 groups and caged separately. The blank control group was initially administered physiological saline by gavage, while the comparative and example groups were initially administered a formulated powder (concentration 1‰, diluted with purified water) by gavage at a dose of 1 mL / 100g rat body weight each time. Rats' body weight was monitored during the experiment, and no decrease was observed. After the experiment, fecal samples were collected on day 28, and propionic acid content was determined using gas chromatography.

[0169] Experimental data are expressed as mean ± standard deviation (mean ± SD). SPSS 16.0 software was used to perform statistical analysis on the experimental data, and one-way ANOVA (Duncan's multiple range test) was used. The specific results are shown in Table 3 below.

[0170] Table 3 Propionic acid content in rat feces

[0171]

[0172] Note: # indicates a comparison with the blank control group, p < 0.05.

[0173] The product contains a certain amount of MCT and nucleotides. The comparison results of the examples and comparative examples show that, compared with the blank control group, although MCT can significantly reduce the propionic acid content, the appropriate combination of nucleotides and MCT has a synergistic effect.

[0174] The final product can be used to alleviate the discomfort experienced by patients with propionic acidemia. This product not only features a specially formulated blend of amino acids tailored to the target population, but also utilizes lipids and nucleotides to synergistically reduce propionic acid levels in the body.

[0175] It should be noted that although the technical solution of the present invention has been described with specific examples, those skilled in the art will understand that the present invention should not be limited thereto.

[0176] The various embodiments of the present invention have been described above. These descriptions are exemplary and not exhaustive, nor are they limited to the disclosed embodiments. Many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the described embodiments. The terminology used herein is chosen to best explain the principles, practical application, or technical improvements to the embodiments in the market, or to enable others skilled in the art to understand the embodiments disclosed herein.

Claims

1. A nutritional composition, characterized in that, The nutritional composition contains plant fat powder and nucleotide components; In the nutritional composition, medium-chain triglycerides (MCTs) account for 20%-40% of the total fatty acids in the composition by weight. Furthermore, based on the weight of the nutritional composition, the nutritional composition contains 0.01-0.15 parts by weight of nucleotide components.

2. The nutritional composition according to claim 1, characterized in that, The nutritional composition contains 0.02-0.1 parts by weight of nucleotides.

3. The nutritional composition according to claim 1 or 2, characterized in that, The nutritional composition contains 30-90 parts by weight of vegetable fat powder, based on the weight of the nutritional composition.

4. The nutritional composition according to any one of claims 1-3, characterized in that, The fat content of the plant fat powder is 30% to 60% by weight.

5. The nutritional composition according to any one of claims 1-4, characterized in that, The nutritional composition also includes amino acids, docosahexaenoic acid (DHA) oil powder, arachidonic acid (RAA) oil powder, complex minerals, and complex vitamins.

6. The nutritional composition according to claim 5, characterized in that, The amino acid composition includes at least one of cystine, histidine, leucine, lysine, phenylalanine, tryptophan, tyrosine, aspartic acid, serine, glutamine, proline, glycine, alanine, and arginine.

7. The nutritional composition according to any one of claims 1-6, characterized in that, The nutritional composition also contains maltodextrin.

8. The use of the nutritional composition according to any one of claims 1-7 in the preparation of products that help improve propionic acidemia and / or methylmalonic acidemia.

9. The application according to claim 8, characterized in that, The aids to improve propionic acidemia and / or methylmalonic acidemia include: the discomfort caused to an individual by propionic acid and / or propionic acid metabolites; Preferably, the aid to improve propionic acidemia and / or methylmalonic acidemia includes reducing the production of propionic acid metabolites and / or lowering the propionic acid content in the individual.

10. The application according to claim 9, characterized in that, The individuals referred to are infants, children, or adults.

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