CN109939135A - A kind of ketogenic parenteral nutrition solution and preparation method thereof - Google Patents

Abstract

The present invention relates to a kind of raw ketone parenteral nutrient solutions and preparation method thereof, including the following substance being dissolved in water for injection: amino acid, lipoid material, glucose, vitamin, minerals, emulsifier and sodium acetate；The mass fraction of each component are as follows: amino acid 1 .80~3.3g/100mL, 6.5~8.0g/100mL of lipoid material, 0.2~0.7g/100mL of glucose, vitamin 28.93mg/100mL, minerals 327.33mg/100ml, 1.32~1.49g/100mL of emulsifier, 2.34~4.29mmol/100mL of sodium acetate.Provided low sugar low amino acid nutrient solution prescription high in fat, for treating intractable epilepsy and other hereditary metabolic disorders such as glucose transporter deficiency disease, pyruvic dehydrogenase deficiency, Partial tumors etc. well, the blank of raw ketone parenteral nutrient solution technology has been filled up.

Description

A kind of ketogenic parenteral nutrition solution and preparation method thereof

technical field

The invention relates to a medical parenteral nutrition preparation, in particular to a ketogenic parenteral nutrition solution and a preparation method thereof.

Background technique

The ketogenic diet is a high-fat and low-carbohydrate diet, which was first proposed by Dr. Wilder of Mayo Clinic in 1921 and applied to the treatment of refractory epilepsy, and achieved good results (Chen Wenjie, Qin Jiong. Ketogenic diet therapy for children Research progress on the mechanism of refractory epilepsy[J]. Chinese Journal of Practical Pediatrics, 2017, 32(24): 1912-1914.). Since then, in other genetic metabolic diseases such as glucose carrier deficiency, pyruvate dehydrogenase deficiency, some tumors (Vidali S, Aminzadeh S, Lambert B, et al. Mitochondria: the ketogenic diet-ametabolism-based therapy. Int J Biochem Cell Biol. 2015; 63: 55-59.), etc., all achieved good results. However, no matter the above-mentioned patients, once they have gastrointestinal obstruction, intestinal fistula, active bleeding and other diseases, they have to fast (Jiao Guangyu, Li Zengning, Chen Wei. Clinical Nutrition [M]. Beijing: People's Health Publishing House) , 2017:106.), the ketogenic diet cannot continue. This situation often makes treatment difficult for clinicians: if normal glucose or amino acids are used for rehydration, the patient's ketone bodies will rapidly decrease, which may induce seizures such as epilepsy that were originally controlled. If the fat emulsion is used alone, it may lead to complications of parenteral nutrition such as nausea, vomiting, and cholestasis. Therefore, the development of scientific, safe and effective ketogenic parenteral nutrition formulas with reasonable proportions is of special significance for ketogenic patients.

All applications involving ketogenic formulations in the Chinese patent database are formulations supplemented by the gastrointestinal tract. To date, there are no patents on ketogenic formulations dedicated to parenteral nutrition (via intravenous infusion).

SUMMARY OF THE INVENTION

The technical problem to be solved by the present invention is to provide a ketogenic parenteral nutrient solution and a preparation method thereof. The high-fat, low-sugar, and low-amino acid nutrient solution formula provided by the present invention can be easily absorbed by the patient when the patient has to fast. Good treatment of refractory epilepsy and other genetic metabolic diseases such as glucose carrier deficiency, pyruvate dehydrogenase deficiency, some tumors, etc., fill the gap of ketogenic parenteral nutrition technology.

The technical solution of the present invention to solve the above-mentioned technical problems is as follows: a ketogenic parenteral nutrition solution, comprising the following substances dissolved in water for injection: amino acids, fatty substances, glucose, vitamins, minerals, emulsifiers and sodium acetate; The mass fraction of components is: amino acid 1.80～3.3g/100mL, fatty substance 6.5～8.0g/100mL, glucose 0.2～0.7g/100mL, vitamin 28.93mg/100mL, mineral 327.33mg/100ml, emulsifier 1.32～ 1.49g/100mL, sodium acetate 2.34～4.29mmol/100mL.

The beneficial effects of the present invention are as follows: the present invention is mainly used for patients who have adopted ketogenic diet to control diseases (such as controlling epilepsy) and fasting when they have severe gastrointestinal dysfunction (such as intestinal obstruction, active bleeding, etc.). At the same time, the state of common parenteral nutrition formulas such as common high sugar and low fat cannot be used, and the present invention can effectively maintain the blood ketone level of fasting children, avoid disease outbreaks, and at the same time ensure total energy intake, which is the best time for ketogenic children during fasting. At the same time, the present invention is a high-fat, low-sugar and low-amino acid formula, which is different from ordinary parenteral nutrition solution high-sugar, low-fat and appropriate amino acid formula. The special needs of energy-supplying nutrients increase the proportion of fat emulsions in parenteral nutrition formula, reduce the proportion of amino acids and glucose, determine the needs of vitamins and minerals, are safe and effective in children, and can maintain the blood of patients after infusion. Ketones are in the ideal range and blood sugar is also in the normal range, do not induce seizures in patients (or induce hyperlactatemia in patients with abnormal glucose metabolism), and effectively meet the nutritional needs of patients taking the ketogenic diet during fasting; the fat of the formula These substances can prevent hyperlipidemia, liver damage, cholestasis, and minimize the adverse reactions of high-fat formulas; the _formula has enhanced doses of vitamin B2, niacin, and pantothenic acid, which can accelerate fat beta oxidation and further reduce fat overload. Possibly; the osmotic pressure of the parenteral nutrition formula is less than 600mOsm/L, which is within the range that the peripheral vein can tolerate (900mOsm/L), the patient feels less pain during infusion, and it is not easy to cause vasculitis; the glucose is medical Glucose in glucose solution, a small amount of glucose solution can balance fat metabolism without affecting ketone production, and at the same time reduce the probability of hypoglycemia; emulsifier makes fatty substances into an absorbable form; the role of minerals is to maintain normal physiological functions of the human body ; The role of amino acids guarantees children's demand for essential amino acids and avoids negative nitrogen balance; Sodium acetate is the mode of existence of anhydrous acetic acid in the final solution, and anhydrous acetic acid is to stabilize the pH of the ketogenic nutrient solution at an acceptable level for the human body within the range to ensure the safety of infusion.

On the basis of above-mentioned technical scheme, the present invention can also do following improvement:

Further, the ratio of the weight of the fat to the sum of the weight of the glucose and the amino acid is 2:1 to 4:1, and the number of the amino acids is 18 or 19.

The beneficial effect of the above-mentioned further scheme is that 19 kinds of amino acids are suitable for children under 3 years old, and 18 kinds of amino acids are suitable for people over 3 years old, which can meet the different needs of patients of different ages for amino acids.

Further, the 18 amino acids are isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, cystine, histidine , tyrosine, alanine, arginine, proline, serine, aspartic acid, glutamic acid and glycine; the mass ratio of various amino acids is isoleucine:leucine:lysine: Methionine: Phenylalanine: Threonine: Tryptophan: Valine: Cystine: Histidine: Tyrosine: Alanine: Arginine: Proline: Serine: Aspart Amino acid: glutamic acid: glycine = 33:56:23:13:19:17:8:31:1:19:9:21:49:27:15:13:20:15.

The beneficial effect of adopting the above-mentioned further scheme is to balance the amino acid pattern and improve the utilization rate of amino acids.

Further, the 19 amino acids are isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, cysteine, histidine acid, tyrosine, alanine, arginine, proline, serine, aspartic acid, glutamic acid, glycine and taurine; the mass ratio of various amino acids is isoleucine:leucine: Lysine: Methionine: Phenylalanine: Threonine: Tryptophan: Valine: Cysteine: Histidine: Tyrosine: Alanine: Arginine: Proline :serine:aspartic acid:glutamic acid:glycine:taurine=33:56:23:13:19:17:8:31:1:19:9:21:49:27:15:13: 20:15:1.

The beneficial effect of adopting the above-mentioned further scheme is to balance the amino acid pattern, improve the utilization rate of amino acids, and meet the amino acid requirements of children under 3 years old at the same time.

Further, the fatty substance is medium chain triglyceride, olive oil, soybean oil and fish oil, and the mass ratio of each component of the fatty substance is medium chain triglyceride: olive oil: soybean oil: fish oil=7: 4:7:2; the emulsifier is egg yolk lecithin, glycerol, and sodium oleate, and the mass ratio of each component of the emulsifier is egg yolk lecithin:glycerol:sodium oleate=43:89:1.

The beneficial effect of adopting the above-mentioned further scheme is that medium-chain fat can be rapidly oxidized into the liver to generate ketone bodies for energy supply, olive oil can provide monounsaturated fatty acids, soybean oil can meet the needs of essential fatty acids, fish oil can regulate immune response and control inflammatory response, and more Mixing these oils in a reasonable proportion can greatly reduce the risk of hyperlipidemia, liver damage and cholestasis caused by this high-fat parenteral nutrition formula; the addition of three emulsifiers enables the oil substances to be effectively emulsified into a form that can be absorbed by the human body.

Further, the vitamins are a mixture of fat-soluble vitamins and water-soluble vitamins, the fat-soluble vitamins are vitamin A, vitamin D ₂ , vitamin E and vitamin K ₁ , and the water-soluble vitamins are vitamin B ₁ , vitamin B ₂ , Niacin, vitamin B ₆ , pantothenic acid, vitamin C, biotin, folic acid and vitamin B ₁₂ , the mass ratio of various vitamins is vitamin A: vitamin D ₂ : vitamin E: vitamin K ₁ : vitamin B ₁ : vitamin B ₂ : Niacin: vitamin B6: pantothenic acid: vitamin C: biotin: folic acid: vitamin B12 = 700: ₁₀ :7000: ₃₀₀ :3800:9000:100000:5000:38000:125000:75:500:6.3.

The beneficial effect of adopting the above-mentioned further scheme is that the doses of vitamin B2, niacin, and pantothenic acid are specially strengthened, which is beneficial to accelerate the β-oxidation of fat and avoid the adverse reactions related to the high-fat formula.

Further, the minerals are sodium, potassium, chlorine, zinc, copper, manganese, selenium, fluorine and iodine, and the mass ratio of each component of the minerals is sodium: potassium: chlorine: zinc: copper: manganese: selenium: Fluorine:Iodine=52000:88000:187000:250:20:1:2:57:1.

The beneficial effect of adopting the above-mentioned further scheme is to ensure that children have different daily requirements for different minerals and maintain normal physiological functions.

A preparation method of a ketogenic parenteral nutrition solution, comprising the following steps:

Step 1: Weigh the corresponding amount of amino acid and the corresponding amount of anhydrous acetic acid and water for injection to prepare an amino acid solution, weigh the corresponding amount of glucose and water for injection to prepare a glucose solution, weigh the corresponding amount of fatty substances, and weigh the corresponding amount of fatty substances. Emulsifier and corresponding amount of sodium hydroxide and water for injection are formulated into fat emulsion;

Step 2: Weigh the corresponding amount of minerals, add the amino acid solution in Step 1 to obtain the first mixed solution;

Step 3: Weigh the corresponding amount of vitamins, and add the fat-soluble vitamins in the vitamins to step 3.

The fat emulsion in step 1 obtains the second mixed solution; the water-soluble vitamins in the vitamins are

Add the glucose solution in step 1 to obtain the third mixed solution;

Step 4: Mix the first mixed solution in step 2 with the second mixed solution and the third mixed solution in step 3 to obtain the ketogenic parenteral nutrition solution.

The beneficial effect of adopting the above-mentioned further scheme is that through reasonable steps, each component can fully function.

Further, the mass concentration of amino acids in the amino acid solution is 6% or 10%, the mass concentration of the glucose solution is 10%, and the mass concentration of oil substances in the fat emulsion is 20%.

The beneficial effect of adopting the above-mentioned further scheme is to select the appropriate concentration and dosage to obtain the ketogenic parenteral nutrition solution of the desired concentration.

Further, it also includes a step of replenishing water. In the step 4, after mixing the first mixed solution, the second mixed solution and the third mixed solution, add water to a certain concentration.

The beneficial effect of adopting the above-mentioned further solution is that the first mixed solution, the second mixed solution and the third mixed solution are mixed and then supplemented with water to obtain a ketogenic parenteral nutrition solution with a desired concentration.

Detailed ways

The principles and features of the present invention are described below, and the examples are only used to explain the present invention, but not to limit the scope of the present invention.

Example 1

This example is 4:1 ketogenic (the weight of fatty substances: the sum of the weight of glucose and amino acids is 4:1), which is suitable for children under 3 years old. The parameters of parenteral ketogenic nutrient solution are energy: 80.3kcal/100ml, osmotic pressure: 421mOsm/L, amino acid 1.8g/100mL, fatty substance 8.0g/100mL, glucose 0.2g/100mL, vitamin 28.93mg/100mL, mineral Substance 327.33mg/ml, emulsifier 1.49g/100mL, sodium acetate 2.34mmol/100mL.

Preparation method of ketogenic parenteral nutrition solution:

Step 1: Weigh corresponding amounts of amino acids and anhydrous acetic acid and water for injection to prepare amino acid solution, take corresponding amounts of glucose and water for injection to prepare glucose solution, weigh corresponding amounts of fatty substances, emulsifier and sodium hydroxide It is formulated into a fat emulsion with water for injection;

Step 2: Weigh the corresponding amount of minerals, add the amino acid solution in Step 1 to obtain the first mixed solution;

Step 3: Weigh the corresponding amount of vitamins, add the fat-soluble vitamins in the vitamins to the fat emulsion in step 1 to obtain a second mixed solution; add the water-soluble vitamins in the vitamins to the glucose solution in step 1, to obtain the third mixed solution;

Step 4: Mix the first mixed solution in step 2 with the second mixed solution and the third mixed solution in step 3, and supplement water for injection to obtain a ketogenic parenteral nutrition solution.

Example 2

This example is 3:1 ketogenic (the weight of fatty substances: the sum of the weight of glucose and amino acids is 3:1), which is suitable for children under 3 years old. The parameters of parenteral ketogenic nutrient solution are energy: 73.6kcal/100ml, osmotic pressure: 428mOsm/L, amino acid 1.98g/100mL, fatty substance 7.1g/100mL, glucose 0.35g/100mL, vitamin 28.93mg/100mL, mineral Substance 327.33mg/ml, emulsifier 1.32g/100mL, sodium acetate 2.57mmol/100mL.

The preparation method of ketogenic parenteral nutrition solution:

Step 1: Weigh corresponding amounts of amino acids and anhydrous acetic acid and water for injection to prepare amino acid solution, take corresponding amounts of glucose and water for injection to prepare glucose solution, weigh corresponding amounts of fatty substances, emulsifier and sodium hydroxide It is formulated into a fat emulsion with water for injection;

Step 2: Weigh the corresponding amount of minerals, add the amino acid solution in Step 1 to obtain the first mixed solution;

Step 3: Weigh the corresponding amount of vitamins, add the fat-soluble vitamins in the vitamins to the fat emulsion in step 1 to obtain a second mixed solution; add the water-soluble vitamins in the vitamins to the glucose solution in step 1, to obtain the third mixed solution;

Step 4: Mix the first mixed solution in step 2 with the second mixed solution and the third mixed solution in step 3, and supplement water for injection to obtain a ketogenic parenteral nutrition solution.

Example 3

This example is 2:1 type ketogenic (weight of fatty substances: the sum of the weight of glucose and amino acid is 2:1), suitable for people over 3 years old, and the parameter of parenteral ketogenic nutrient solution is energy: 79.6kcal/100ml, Osmotic pressure: 554mOsm/L, amino acids 3.3g/100mL, fatty substances 7.2g/100mL, glucose 0.3g/100mL, vitamins 28.93mg/100mL, minerals 327.33mg/ml, emulsifier 1.34g/100mL, sodium acetate 4.29 mmol/100mL.

Preparation method of ketogenic parenteral nutrition solution:

Step 1: Weigh corresponding amounts of amino acids and anhydrous acetic acid and water for injection to prepare amino acid solution, take corresponding amounts of glucose and water for injection to prepare glucose solution, weigh corresponding amounts of fatty substances, emulsifier and sodium hydroxide It is formulated into a fat emulsion with water for injection;

Step 2: Weigh the corresponding amount of minerals, add the amino acid solution in Step 1 to obtain the first mixed solution;

Step 3: Weigh the corresponding amount of vitamins, add the fat-soluble vitamins in the vitamins to the fat emulsion in step 1 to obtain a second mixed solution; add the water-soluble vitamins in the vitamins to the glucose solution in step 1, to obtain the third mixed solution;

Step 4: Mix the first mixed solution in step 2 with the second mixed solution and the third mixed solution in step 3, and supplement water for injection to obtain a ketogenic parenteral nutrition solution.

Example 4

This example is 2.5:1 type ketogenic (the weight of fatty substances: the sum of the weight of glucose and amino acid is 2.5:1), suitable for people over 3 years old, and the parameters of the parenteral ketogenic nutrient solution are energy: 68.9kcal/100ml, Osmotic pressure: 477mOsm/L, amino acids 1.9g/100mL, fatty substances 6.5g/100mL, glucose 0.7g/100mL, vitamins 28.93mg/100mL, minerals 327.33mg/ml, emulsifier 1.34g/100mL, sodium acetate 2.47 mmol/100mL.

The preparation method of ketogenic parenteral nutrition solution:

step 1:

Step 1: Weigh corresponding amounts of amino acids and anhydrous acetic acid and water for injection to prepare amino acid solution, take corresponding amounts of glucose and water for injection to prepare glucose solution, weigh corresponding amounts of fatty substances, emulsifier and sodium hydroxide It is formulated into a fat emulsion with water for injection;

Step 2: Weigh the corresponding amount of minerals, add the amino acid solution in Step 1 to obtain the first mixed solution;

Step 3: Weigh the corresponding amount of vitamins, add the fat-soluble vitamins in the vitamins to the fat emulsion in step 1 to obtain a second mixed solution; add the water-soluble vitamins in the vitamins to the glucose solution in step 1, to obtain the third mixed solution;

Step 4: Mix the first mixed solution in step 2 with the second mixed solution and the third mixed solution in step 3, and supplement water for injection to obtain a ketogenic parenteral nutrition solution.

Example 5

This example is 3.5:1 type ketogenic (the weight of fatty substances: the sum of the weight of glucose and amino acids is 3.5:1), suitable for people over 3 years old, and the parameters of the parenteral ketogenic nutrient solution are energy: 68.9kcal/100ml, Osmotic pressure: 436mOsm/L, amino acids 1.84g/100mL, fatty substances 7.91g/100mL, glucose 0.42g/100mL, vitamins 28.93mg/100mL, minerals 327.33mg/ml, emulsifier 1.48g/100mL, sodium acetate 2.39 mmol/100mL.

Preparation method of ketogenic parenteral nutrition solution:

Step 1: Weigh corresponding amounts of amino acids and anhydrous acetic acid and water for injection to prepare amino acid solution, take corresponding amounts of glucose and water for injection to prepare glucose solution, weigh corresponding amounts of fatty substances, emulsifier and sodium hydroxide It is formulated into a fat emulsion with water for injection;

Step 2: Weigh the corresponding amount of minerals, add the amino acid solution in Step 1 to obtain the first mixed solution;

Step 3: Weigh the corresponding amount of vitamins, add the fat-soluble vitamins in the vitamins to the fat emulsion in step 1 to obtain a second mixed solution; add the water-soluble vitamins in the vitamins to the glucose solution in step 1, to obtain the third mixed solution;

Step 4: Mix the first mixed solution in step 2 with the second mixed solution and the third mixed solution in step 3, and supplement water for injection to obtain a ketogenic parenteral nutrition solution.

It should be noted that the above-mentioned amino acid solution, glucose solution and fat emulsion can be purchased commercially, and can be directly used for preparation according to the required amount after purchase; or commercial customization: a solution of a specific concentration is customized to the manufacturer, and the manufacturer obtains it through the existing technology. Corresponding concentrations of amino acid solution, glucose solution and fat emulsion.

In the prior art, the process of preparing amino acids into amino acid solutions includes weighing corresponding amounts of amino acids, anhydrous acetic acid and water for injection to prepare amino acid solutions through steps such as stirring, filtration, freezing, and drying; the process of preparing glucose into glucose solutions. Including weighing the corresponding amount of glucose, adding water for injection, stirring to prepare a glucose solution; weighing the corresponding amount of fatty substances and emulsifiers to prepare oil phase and water phase, then stirring and mixing, adding sodium hydroxide, adding water for injection, Steps such as homogenization are formulated into a fat emulsion.

In the preparation method of the above-mentioned ketogenic parenteral nutrition solution, in step 3, the fat-soluble vitamins in the vitamins are added to the fat emulsion in step 1 to obtain a second mixed solution; the water-soluble vitamins in the vitamins are added in step 1 in the glucose solution to obtain the third mixed solution. If the vitamins in claim 1 are only fat-soluble vitamins, then step 3 only includes adding the fat-soluble vitamins in the vitamins to the fat emulsion in step 1 to obtain a second mixed solution, and then adding the first mixed solution and the second mixed solution. It is mixed with glucose solution (replenish water if necessary) to obtain ketogenic parenteral nutrition solution. If the vitamins in claim 1 are only water-soluble vitamins, then step 3 only includes adding the water-soluble vitamins in the vitamins to the glucose solution in step 1 to obtain a third mixed solution, and then adding the first mixed solution, the fat emulsion and the first mixed solution. The three mixed solutions are mixed, (replenish water if necessary) to obtain a ketogenic parenteral nutrition solution.

The anhydrous acetic acid of the corresponding amount and the sodium hydroxide of the corresponding amount refer to the acetic acid and the sodium hydroxide having the same mole number as the sodium acetate in the required nutrient solution; the mixing of the first mixed solution and the second mixed solution in step 4, The acetic acid and sodium hydroxide are reacted to form sodium acetate in the nutrient solution.

The amino acid of the amino acid solution is preferably formulated at a mass concentration of 6% or 10%, the glucose solution is preferably formulated at a mass concentration of 10%, and the oil in the fat emulsion is preferably formulated at a mass concentration of 20%. When there are 19 kinds of amino acids, the preferred preparation mass concentration of the amino acid solution is 6%; when there are 18 kinds of amino acids, the preferred preparation mass concentration of the amino acid solution is 10%.

In the present invention, each substance is weighed according to the required weight, and weighing instruments with different precisions are used for weighing. For substances that need to be weighed to the tenth place, choose an electronic balance that is accurate to 0.1g. For substances that need to be weighed to the percentile, choose an electronic balance that is accurate to 0.01g. 0.001g electronic balance.

The present invention formulates the time, speed and monitoring index of use: the continuous use time of the nutrient solution of the present invention is required not to exceed 2 weeks; the infusion time is determined according to the amount of fat, and the infusion time (hour) of a certain amount of fat is not shorter than the specified amount of fat. The weight of fatty substances to be infused/0.15/body weight (wherein the mass of fatty substances is in g, and the body weight is in kg). It is necessary to review liver and kidney function, electrolytes, blood lipids, blood sugar, blood ketone levels, etc. every week to decide whether to continue use.

The present invention establishes the indications and contraindications for use. Indications: refractory epilepsy, glucose carrier deficiency, pyruvate dehydrogenase deficiency, etc. Contraindications: all diseases related to fat utilization disorders, acute phase of amino acid metabolism diseases, severe liver and kidney function damage, etc., chronic metabolic acidosis, hyperlipidemia, hypertension or diseases that cannot be used after evaluation by clinicians, etc.

When the ratio of the weight of the fatty substance to the sum of the weight of the glucose and the amino acid is 2:1 to 4:1, the ketogenic effect is better.

In clinical practice, 4:1 type, 3:1 type and 2:1 type of ketosis are the most widely used, which can be selected according to the patient's situation, or other ketogenic ratios can be selected according to the patient's situation.

Effect description

Patient Application Example 1

The child Zhang Moumou, male, in November, suffered from infantile spasms (the onset of ketogenic milk treatment started in August), and was admitted to the hospital because of "abdominal pain, abdominal distension, and vomiting for 1 day". Fluid level; the doctor considered the main diagnosis as 1. Complete intestinal obstruction 2. Infantile spasms; after treatment, the condition was stable and short-term parenteral nutrition support was needed. At this time, the nutritionist intervened to formulate a nutritional plan: the child weighed 8kg, and the current space for parenteral nutrition was 330ml. Children usually use 4:1 ketogenic milk for treatment, so the above 4:1 ketogenic parenteral nutrition formula (under 3 years old) is used to start parenteral nutrition infusion with a total of 330ml to ensure nutritional intake, and the infusion rate is 15ml /h, supply and demand infusion for 22 hours. The infusion continued for a total of 5 days, and the blood ketones and blood glucose were monitored every day. After 5 days of treatment, the intestinal obstruction was gradually relieved, and the ketogenic milk was increased and the ketogenic parenteral nutrition solution was reduced. After 2 weeks, the patient was discharged from the hospital and continued to be fed with ketogenic milk. The clinical nutrition clinic was followed up.

Patient application example 2

The child Wang Moumou, female, 4 years old, 2, with refractory epilepsy (started ketogenic diet treatment at the age of 3), was admitted to the hospital because of "upper abdominal pain for 10 hours, accompanied by nausea and vomiting"; blood amylase was checked at 1066U. /L, lipase 4213U/L. Blood routine showed: WBC15.77×109/L, N0.733. Upper abdominal CT results showed acute pancreatitis. The main diagnosis is 1. acute pancreatitis 2. refractory epilepsy; after the vital signs are stable after treatment, short-term parenteral nutrition support is needed, please consult the nutrition department: the child weighs 15kg, and the current parenteral nutrition solution space is 520ml. The child has usually used a 2:1 homemade meal for three meals, self-measured blood ketones 2.7-4.5 mmol/L, blood sugar 3.6-5.2 mmol/L, and the condition is under stable control. Although severe pancreatitis can also be fed with high-sugar and low-fat short peptide enteral formula by nasojejunal tube, the child is a patient with refractory epilepsy treated with long-term ketogenic diet, and this method may lead to epilepsy. attack. Therefore, fasting was continued in the short term, and the above-mentioned 2:1 ketogenic parenteral nutrition formula (over 3 years old) was used to start parenteral nutrition infusion (liquid 520ml), the infusion rate was 38ml/h, and the supply and demand infusion was 13.6 hours. The continuous infusion time was 13 days, and the blood ketone and blood sugar were monitored every day. At the end of the first week, the levels of transaminase, bilirubin and blood triglyceride were not significantly higher than those at the time of admission. Before discharge, the nutritionist should consult again: Considering that the child has low seizure frequency and stable disease control, but long-term ketogenic diet may be one of the predisposing factors for pancreatitis, it is recommended to gradually reduce the proportion of ketogenic diet and gradually restore normal diet.

The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included in the protection of the present invention. within the range.

Claims (10)

1. a ketogenic parenteral nutrition solution, is characterized in that, comprises the following material dissolved in water for injection: amino acid, fatty substance, glucose, vitamin, mineral, emulsifier and sodium acetate; The mass fraction of each component is: amino acid 1.80～3.3g/100mL, fatty substance 6.5～8.0g/100mL, glucose 0.2～0.7g/100mL, vitamin 28.93mg/100mL, mineral 327.33mg/100mL, emulsifier 1.32 ~1.49g/100mL, sodium acetate 2.34~4.29mmol/100mL. 2 . The ketogenic parenteral nutrition solution according to claim 1 , wherein the ratio of the weight of the fatty substance to the sum of the weight of the glucose and the amino acid is 2:1 to 4:1, 2 . The amino acids are 18 or 19. 3. a kind of ketogenic parenteral nutrition solution according to claim 2, is characterized in that, described 18 kinds of amino acids are isoleucine, leucine, lysine, methionine, phenylalanine, Threonine, tryptophan, valine, cystine, histidine, tyrosine, alanine, arginine, proline, serine, aspartic acid, glutamic acid, and glycine; each The mass ratio of the amino acids is isoleucine:leucine:lysine:methionine:phenylalanine:threonine:tryptophan:valine:cystine:histidine:tyrosine Amino acid: Alanine: Arginine: Proline: Serine: Aspartic acid: Glutamic acid: Glycine = 33:56:23:13:19:17:8:31:1:19:9: 21:49:27:15:13:20:15. 4. a kind of ketogenic parenteral nutrition solution according to claim 2, is characterized in that, described 19 kinds of amino acids are isoleucine, leucine, lysine, methionine, phenylalanine, Threonine, tryptophan, valine, cysteine, histidine, tyrosine, alanine, arginine, proline, serine, aspartic acid, glutamic acid, glycine and bovine Sulfonic acid; the mass ratio of various amino acids is isoleucine:leucine:lysine:methionine:phenylalanine:threonine:tryptophan:valine:cysteine: Histidine:tyrosine:alanine:arginine:proline:serine:aspartic acid:glutamic acid:glycine:taurine=33:56:23:13:19:17:8 :31:1:19:9:21:49:27:15:13:20:15:1. 5. a kind of ketogenic parenteral nutrition solution according to claim 1, is characterized in that, described fatty substance is medium-chain triglyceride, olive oil, soybean oil and fish oil, and each component of described fatty substance is The mass ratio is medium chain triglyceride: olive oil: soybean oil: fish oil = 7:4:7:2; the emulsifier is egg yolk lecithin, glycerol, and sodium oleate, and the mass ratio of each component of the emulsifier is For egg lecithin: glycerol: sodium oleate = 43:89:1. 6. A ketogenic parenteral nutrition solution according to claim 1, wherein the vitamin is a mixture of a fat-soluble vitamin and a water-soluble vitamin, and the fat-soluble vitamin is vitamin A, vitamin D ₂ , vitamin E and vitamin K ₁ , the water-soluble vitamins are vitamin B ₁ , vitamin B ₂ , niacin, vitamin B ₆ , pantothenic acid, vitamin C, biotin, folic acid and vitamin B ₁₂ , and the mass ratio of various vitamins is vitamin A: Vitamin D ₂ : Vitamin E: Vitamin K ₁ : Vitamin B ₁ : Vitamin B ₂ : Niacin: Vitamin B ₆ : Pantothenic acid: Vitamin C: Biotin: Folic acid: Vitamin B ₁₂ =700:10:7000:300:3800: 9000:100000:5000:38000:125000:75:500:6.3. 7. a kind of ketogenic parenteral nutrition solution according to claim 1, is characterized in that, described mineral is sodium, potassium, chlorine, zinc, copper, manganese, selenium, fluorine and iodine, and each group of described mineral The mass ratio of the points is sodium:potassium:chlorine:zinc:copper:manganese:selenium:fluorine:iodine=52000:88000:187000:250:20:1:2:57:1. 8. a preparation method of the ketogenic parenteral nutrition solution described in any one of claims 1-7, is characterized in that, comprises the steps: Step 1: take by weighing the corresponding amount of amino acid and corresponding amount of anhydrous acetic acid and water for injection to prepare amino acid solution, take by weighing corresponding amount of glucose and water for injection to prepare glucose solution, take by weighing corresponding amount of fatty substances, corresponding amount of Emulsifier and corresponding amount of sodium hydroxide and water for injection are formulated into fat emulsion; Step 2: Weigh the corresponding amount of minerals, add the amino acid solution in Step 1 to obtain the first mixed solution; Step 3: Weigh the corresponding amount of vitamins, add the fat-soluble vitamins in the vitamins to the fat emulsion in step 1 to obtain a second mixed solution; add the water-soluble vitamins in the vitamins to the glucose solution in step 1, to obtain the third mixed solution; Step 4: Mix the first mixed solution in step 2 with the second mixed solution and the third mixed solution in step 3 to obtain the ketogenic parenteral nutrition solution. 9. The preparation method of the ketogenic parenteral nutrition solution according to claim 8, wherein the amino acid mass concentration in the amino acid solution is 6% or 10%, and the glucose solution concentration mass concentration is 10%, The mass concentration of oil substances in the fat emulsion is 20%. 10. the preparation method of ketogenic parenteral nutrition solution according to claim 9, is characterized in that, also comprises the step of replenishing moisture, in described step 4, the first mixed solution, the second mixed solution and the third mixed solution are After mixing, add water for injection to a certain concentration.