TW526065B - Fatty emulsions containing reducing sugar and method for sterilizing the same - Google Patents

Abstract

A fatty emulsion containing a reducing sugar, being an oil-in-water emulsion prepared by emulsifying a fat or oil with an emulsifying agent wherein the aqueous phase contains both a reducing sugar and a buffer consisting of an organic acid exhibiting an acid dissociation constant of 5.0 to 7.5 in water, a salt thereof and the pH is adjusted to 5.0 to 7.5; a fatty emulsion containing a reducing sugar, and a liquid medicine of fat or oil and that is sterilized after carbon dioxide is dissolved therein and then is held in a plastic injection container; the plastic injection container is packaged with a carbon dioxide absorbent in an oxygen-impermeable secondary container; and a process for the production of a method for sterilizing the same. This fatty emulsions which is stable, of high quality, and containing reducing sugar can suppress the formation of free fatty acids and in decomposition of the sugar that both lead to color variation, thus being high-quality stable ones little causing discoloration.

Description

526065 A7 B7 V. Description of the invention (1) Field of the invention The present invention relates to a fat-reducing milk containing reducing sugar for intravenous injection, such as an intravenous hyperalimentation, especially a high-quality stable fat milk, regardless of Whether it contains reducing sugars can reduce the formation of free fatty acids and inhibit the discoloration caused by the decomposition of reducing sugars during the heat sterilization process and its sterilization method. BACKGROUND OF THE INVENTION Many patients are unable to eat orally due to gastrointestinal surgery. The nutritional management of such patients is generally through a central vein intravenous hypertrophy (IVH). This IVH is very effective in maintaining the nutritional status of such patients and can promote recovery and treatment, so it is widely used in the field of surgical treatment. At the same time, IVH has strict requirements for program control, and there are some disadvantages such as the risk of infection and metabolic episodes such as hyperglycemia. Therefore, the current trend is to feed from the surrounding veins as much as possible. Even if intravenous overnutrition is disabled in these patients, their nutritional status before surgery and the degree of surgical infection are relatively mild, and the time when those patients are unable to eat by mouth will not Too long. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page)

Regardless, it not only supplies carbohydrates, amino acids, and electrolytes, but also provides fats that are essential for patient nutrition management. Especially when feeding via peripheral veins, fat emulsions must be used as part of the energy source to meet the calorie requirement, but prevent osmotic pressure from increasing as much as possible by injection. At the same time, the ideal dosage form such as the over-nutrition method is a pack of doses. 2 This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 526065 A7 B7. 5. Description of the invention (2) It includes all Ingredients in one package. However, it is known that sugars and amino acids undergo a Meillard reaction to cause browning, and that fatty milk and an electrolyte, especially multivalent cations, appear simultaneously, causing aggregation of emulsion particles. Therefore, these ingredients cannot be contained in the same package, and generally an attempt is made to provide a double-packed dosage form, including one reducing sugar and fat milk as one package, and the other package as amino acid and electrolyte. However, a reducing sugar aqueous solution such as glucose can decrease pH 値 due to sterilization, time after sterilization, and mixing with fat milk. The decrease in pH 値 will cause hydrolysis of fats and emulsifiers to produce free fatty acids. This free fatty acid is clearly associated with adverse reactions to fatty milk formulations such as fever and headache. Therefore, the presence of free fatty acids should be avoided as much as possible. The pH was reduced by sterilization and free fatty acids were fatal to the mixture. In order to overcome the above shortcomings, we researched in many aspects, but often got dissatisfied results. Therefore, try to add histidine (L-histidine) and / or tris (hydroxymethyl) aminomethane as a buffer solution containing reducing sugar fatty milk to avoid the increase of free fatty acid concentration (not reviewed in Japan Patent Publication No. H5-65220), but this method cannot completely avoid the generation of free fatty acids. Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page). To solve the above problem, phosphate was added to the reducing sugar-containing fat milk to a final concentration of 3 mM to 20 mM (Japan Unexamined Patent Publication No. H7-277989), but because the emulsion particles are particularly agglomerated after heat sterilization, 4 this method is not suitable as a stable product and provides a high-quality milk \: 齐 (j 〇, _ In addition, containing One of the disadvantages of reducing sugar fat milk is that it will be produced due to heat sterilization and long-term paper size applicable to Chinese National Standards (CNS) 84 (21 × 297 mm) 526065 A7 ___ B7 V. Description of the invention (3) Decomposition products make the emulsion have a light color. In order to eliminate this disadvantage, it is generally to maintain the fat milk at a low pH, but in fact, when given a high dose of fat milk, its pH is not suitable and the pH of the circulating blood is too different For this reason, the pH of reducing milk containing reducing sugars is traditionally controlled between 5 and 7.5 and is adjusted separately from the pH to add a coloring inhibitor such as dithioglycerol or dithiothreo Alcohol to avoid the combination of the above coloring and reducing sugars (for example, Japanese Unexamined Patent Publication No. Η 5-9 1 1 2). However, it is best not to and should avoid adding ingredients that are inappropriate for the excessive nutrition method such as color inhibition Moreover, one disadvantage of this injection is the smell of sulfur in the coloring inhibitor. Therefore, the industry is very much looking forward to the development of a non-coloring inhibitor and no discoloration problems caused by the decomposition of reducing sugars, as well as inhibiting the release Reduced sugar-containing fat milk produced by fatty acids. The object of the present invention is to develop and provide an improved stable sugar-containing fat-containing milk and an industry long-awaited production technology. The emulsion mimics the physiological pH and has no or inhibited reduction due to reduction. The problem of discoloration due to sugar decomposition, with the help of no coloring inhibitors, inhibits the production of free fatty acids and prevents the aggregation of emulsion particles of conventional fat milk defects. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the first Please fill in this page again for attention) In order to achieve the above-mentioned purpose, the inventor of this case first explored adding a wide range. It is found that the use of a certain organic acid or a salt thereof in a certain pH range can completely determine the increased stability of the reducing sugar-containing fat emulsion. In addition, the inventors of the present case have shown that before heat sterilization, a reducing sugar is contained. The PH 値 (pH 値 approximately 5.0-7.5) of Heyi Fat Milk Drug System was temporarily lowered due to dissolving carbon dioxide gas in it. Then, the paper size of the carbon dioxide gas is in accordance with Chinese National Standard (CNS) A4 (210X297 mm) Ministry of Economic Affairs Central Bureau of Standards Consumer Cooperation Du printed 526065 A7 B7 __ V. Description of the Invention (4) The experience is removed from the drug system, which can inhibit the decomposition of reducing sugars during heat sterilization and storage, and at the same time, even in the absence of coloring inhibitors In the presence, coloration can also be suppressed to obtain a satisfactory reducing sugar-containing fat emulsion. Furthermore, the inventors of the present case have discovered that the use of a carbon dioxide gas absorber after thermal sterilization can quickly remove carbon dioxide gas from the drug system, and the use of a carbon dioxide gas absorber can also prevent the adverse effects of oxygen on the drug system. Therefore, inhibiting the reduction of reducing sugars during thermal sterilization and storage can not only avoid discoloration of the emulsion, but also avoid the production of free fatty acids. The development of this case is based on the above findings. The invention discloses that the present invention provides a reducing sugar-containing fat emulsion, including an oil-in-water fat emulsion emulsified by a fat and an emulsifier, wherein a reducing sugar and at least one selected from the group consisting of an acid dissociation index in water ranging from 5.0- The organic acid buffer substance of 7.5 and its salts are present in the water phase at the same time, and the pH of the emulsion is adjusted between 5.0 and 7.5. Another object of the present invention is to provide a reducing sugar-containing fat milk, which comprises a reducing sugar and a fat medical liquid, carbon dioxide is dissolved therein and sterilized and packed in a plastic injection container (hereinafter referred to as a primary container) ... The plastic injection container is packaged with a carbon dioxide gas absorber in an outer container that is completely impermeable to oxygen (hereinafter referred to as a secondary container). Still another object of the present invention is to provide a method for sterilizing fat milk containing reducing sugar, which comprises sterilizing a medical liquid containing a reducing sugar and a fat and carbon dioxide in one of them. The present invention also provides a killing method using the sterilization method. The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before filling this page)

1T / M \ Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 526065 A7 B7 V. Description of the invention (5) Bacterial milk containing reducing sugar. The fat milk containing the reducing sugar fat milk component of the present invention is not different from the fat milk conventionally used for intravenous feeding, that is, an oil-in-water fat emulsion prepared by emulsifying the fat component and an emulsifier. . The fat used in this emulsion can be any of the oils and fats traditionally used as a calorie source (energy source) for over-nutrition, etc., and thus includes various vegetable oils such as soybean oil, cottonseed oil, safflower oil, corn oil, coconut Oil, perilla oil, styrax oil, linseed oil, etc., fish oils such as sardine oil, cod oil, etc., are long-chain fatty acid triglycerides (LCT) of essential fatty acid sources, and are usually 8-10 carbon and have It is easy to absorb and burn, and it is not easy to aggregate. Typical medium chain fatty acid triglycerides (MCT) such as PanaceteTM (NOF Corporation) and ODOTM (Nisshin Oil Mills Ltd.) are typical examples. Furthermore, the fat includes a chemically defined triglyceride such as 2-linoleoyl-1,3-dioctanoylglycerol, 2-linoleoleic acid 1,3-didecyl Acid glycerol (2-linoleoyl-1, 3-didecanoylglycerol) and the like. These substances can be used alone or in combination. The final concentration of fat added to the product of this case is preferably about 1.5-20 w / v%, or the best result is 2-8 w / v%. The emulsifier can also be any commonly used emulsifier, such as phospholipids such as egg yolk lecithin, hydrogenated egg yolk lecithin, soybean lecithin, hydrogenated soybean lecithin, etc., and synthetic surface active agents (such as commercially available products Tween 80, HC Ο -6 0, P1 ur ο nic F 6 8 etc.). The proportion of emulsifier is not so important, but the preferred is 30-300 mg per gram of fat. Reducing sugar, which is another energy source in the reducing sugar-containing fat milk of the present invention, can be any sugar traditionally used for such injections. A better example is the Portuguese paper size applicable to the Chinese National Standard (CNS) A4 specification ( 210 × 297 mm)

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Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, 1T. 526065 A7 B7_ ______ 5. Description of the invention (6) Glucose, fructose and maltose. Those sugars can be used alone or in combination. The reducing sugar may be added during or after emulsification of the fat emulsion. The ratio of the reducing sugar is generally 5-50 w / v%, preferably in the range of 6-25 w / v ° / 〇. From a blood glucose standpoint, glucose is best used. If necessary, non-reducing sugars such as xylitol, sorbitol 'glycerol, etc. may be added to the ingredients of the present invention at an appropriate concentration. In the pharmaceutical composition of the present invention, it is very important to add at least one buffer substance selected from organic acids in water with an acid dissociation index ranging from 5.0 to 7.5 and salts thereof. The organic acids used may be selected from a wide range of aliphatic or aromatic Group carboxylic acids, sulfonic acids, phosphoric acids and the like are preferably carboxylic acids. Those organic acids may be monovalent or polyvalent, and some special words are mentioned. The organic acids include succinic acid, malonic acid, glutaric acid, maleic acid, malic acid and the like, and succinic acid is preferred. The term "acid dissociation index" as used herein means the acid dissociation constant (pKa) in water at room temperature. Taking a dicarboxylic acid as an example, it means the dissociation index of the second phase. In tricarboxylic acid, the The word means the dissociation index of the third phase. As for the above-mentioned organic acid salts, alkali metal salts such as sodium salt, potassium salt, and the like, and magnesium salts are typical examples. The content of the buffer substance depends on the amount of reducing sugar and fat, and in general, it is preferably in the range of 0.00 5 to 0.0 5 w / v% of the total component. When the buffer substance is a free acid, the pH of the reducing sugar-containing fat emulsion of the present invention is adjusted to between 5.0 and 7.5 with a base. Bases typically used for this purpose include hydroxides of alkali metals such as sodium hydroxide and potassium hydroxide. On the other hand, when an organic acid salt is used as the buffer substance, the pH of the emulsion is adjusted to the above-mentioned range with an acid or an alkali. The acids used may include, but are not limited to, hydrochloric acid, sulfuric acid, and acetic acid. The base is the same as the above. The maximum 7 ^ 's scale is applicable to China National Standard (CNS) A4 specifications (210X297 mm)

Printed by the Employees' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 526065 A7 B7 V. Description of the invention (7) The optimal pH range is between 5.5 and 6.5. Therefore, the obtained reduced sugar-containing fat milk of the present invention can be used as a final product. However, in fact, the emulsion is generally used together with other ingredients such as amino acids and electrolytes. The fat milk is preferably supplied in a double-packed dosage form. Therefore, the emulsion is installed in multiple compartments which are separated from each other to prevent the compartments from communicating with each other. The amino acid and electrolyte are contained in one compartment in the container, and the contents of the two compartments can be mixed by piercing or breaking the separator before use. Some examples of such multiple compartment containers are (1) a container containing a heat-sealable easily separable separator (Japanese Unexamined Patent Publication No. H2-4671, Japanese Unexamined New Publication No. H5-5 13 8), \ 2) A container provided with a spacer formed by clamping with a clip (Japanese Unexamined Patent Publication No. S63-309263), and (3) a container including a spacer using a communication element (Japanese Unexamined Patent Publication No. S63- 205 50). Among these, the first-mentioned container (1) is preferable because it is suitable for high production and easily communicates the compartments. '' The above container is preferably made of a breathable plastic material such as traditionally used for medical containers. Specific examples are polyethylene, polypropylene, polyvinyl chloride, crosslinked ethylene vinyl acetate copolymer, and ethylene a-olefin copolymerization. Materials, mixtures of these copolymers, and thin films of these polymers. The ingredients are filled into each compartment according to a conventional procedure and then sterilized. For example, each ingredient liquid is charged into the compartment in the presence of an inert gas such as carbon dioxide or nitrogen 'and sealed, and then heat sterilized together. Thermal sterilization methods include various known methods such as autoclaving, hot water sterilization, and hot shower sterilization. If necessary, heat sterilization can be stored in an inert gas such as nitrogen. 8 This paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm).

526065 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 V. Description of Invention (8) Fatty milk containing 3® raw sugar is first packed in a 'stage' container in the form of an injection solution, and then packed with an oxygen absorber in a secondary container which is completely impermeable to oxygen to avoid decomposition and oxidation of the injection solution as much as possible. Especially when using the above-mentioned first container (1), it is preferably packed in a secondary container with the separator folded, so that the separator does not break due to external pressure, and the compartments may communicate. Furthermore, if necessary, the above-mentioned packaging can be performed by an inert gas filling packaging method. The airtight packaging material suitable for secondary packaging may be any container known to have gas barrier properties, including but not limited to polyethylene, polyethyleneterephthalate (PET), polyethylene naphthalate (PEN), Ethylene, Ethylene; Ethyl alcohol copolymer (EVOH), polyvinylidene chloride (PVDC), nylon and polyester. The secondary container is preferably made of a material selected from the above materials. Cast or made of any thin film or sheet of the material, a thin layered film or sheet of the material, or a thin film or sheet of a vapor-deposited layer of silicon or aluminum. More preferably, it is made of a multilayer film. The absorber includes various known materials such as iron or iron compounds such as iron hydroxide, iron oxide, iron carbide, etc. as an activating ingredient. This typical commercially available product is "Ageless" (manufactured by Mitsubishi Gas Chemical), "Moduran" ( Nippon Kayaku) and "Secur" (Nippon Soda). When installed and sealed in the presence of carbon dioxide gas and then heat sterilized under nitrogen, release one or two oxygen The carbon gas absorber is more suitable in the second container to completely remove the residual carbon dioxide (in space and medical fluids 9 paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) (please read the back first) Please note that this page is to be filled out again.) Order 526065 Printed by the Consumer Standards Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 V. Invention Description (9)). The above carbon dioxide gas absorbers include commercially available products such as those of Wako Pure Chemical Industries. " Wakolime ", Mitsubishi Gas Chemical's product" Ageless E ", Aica Kogyo's product" Baralyme "o When the reducing sugar-containing fat emulsion of the present invention is administered, other ingredients such as vitamins and trace elements (minerals) can be added as appropriate. This vitamin Includes various vitamins, whether water-soluble or fat-soluble, such as retinol palmitate, thiamine hydrochloride, riboflavine, hydrochloride atLn polyol (pyridoxine hydrochloride) , Cyanocobalamine, ascobicacid, cholecalcif eroi), tocopherol acetate, nicotinamide, 15 pantothenate, folic acid, biotin, and phytonadione. The present invention further provides a reducing sugar-containing fat milk, which includes a reducing sugar and a fat medical liquid, carbon dioxide is dissolved therein and sterilized, and then packed in a plastic injection container, and then packaged with a carbon dioxide gas absorber in oxygen A completely impermeable secondary container, and a method for sterilizing the fat emulsion. . · Through the use of carbon dioxide gas sterilization program and the carbon dioxide gas absorber used with this case can provide a reducing sugar-containing fat milk at physiological pH, without the help of coloring inhibitors, can properly prevent its discoloration and Free fatty acids are formed. Furthermore, the use of an oxygen absorber has a positive effect on preventing discoloration of the injection solution and the production of free fatty acids. 10 This paper size applies Chinese National Standard (CNS) Α4 specification (210 × 297 mm) (Please read the precautions on the back before filling this page), -ιτ

526065 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs V. Invention Description (10 With the help of carbon dioxide gas, in addition to the above-mentioned medical liquid sterilization procedures, carbon dioxide must be dissolved in order to reduce its pH and sterilization in advance, Other operating conditions such as sterilization time and temperature can be similar to those used in traditional sterilization techniques. Preferably it is 102-121. (: Sterilization at temperature for 20-60 minutes. The effect of carbon monoxide gas dissolving in medical liquids is enriched by carbon dioxide Pleum in a preparation tank containing a medical liquid until the liquid reaches the desired pH 値, and then give a mixed gas (such as nitrogen-carbon dioxide gas air-carbon dioxide gas) with a partial pressure of carbon dioxide gas or Under proper pressure or atmospheric pressure, only carbon dioxide gas is passed to maintain the above pH 値, and then the medical liquid is filled into a primary container including a plastic injection container such as a blood transfusion bag, an injection bottle, etc., and a similar mixed gas or carbon dioxide is used. The gas is removed from the gas, and then the primary container is sterilized by high-pressure steam, hot water, or The hot water shower sterilization method is used to complete the sterilization. As long as the reducing sugar can be decomposed due to the sterilization process, the above pH value is not very important, but generally it is preferably in the range of pH 4-6.5. In the sterilization method of the present invention In the medical solution, the carbon dioxide gas will be gradually released during and after the sterilization process, so that the pH of the sterilized injection solution will eventually return to the pH near the sterilization. Therefore, the benefits of the pharmaceutical ingredients of the present invention It can avoid the danger of decomposition caused by the acidification of the liquid to form free fat and fatty acid. Therefore, the plastic injection bag containing the injection solution in this case is preferably made of a breathable plastic material traditionally used for medical containers and tubes. This container material Specific examples of the above have been mentioned in the previous article. When the plastic injection container containing the medical liquid is packaged in a secondary container with a gas barrier property, the above-mentioned complete release of carbon dioxide gas will become quite difficult. The pH of the liquid continues to tend to fall in the acidic range exceeding 11. The paper size applies the Chinese National Standard (CNS) Α4 size (210X 297 mm) (please read first Note to fill out the back of this page)

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Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 526065 A7 B7___ 5. The extended time of the invention description (11), so that reducing sugars form 5-hydroxymethyl-2-furfural (5-HMF ) And increase the risk of forming free fatty acids. In the present invention, in order to positively inhibit the formation of 5-HMF and free fatty acids, the plastic injection container containing the sterilized medical liquid is packaged together with a carbon dioxide gas absorber and an oxygen absorber in a fully air-impermeable secondary container. With this procedure, the pH of the medical liquid can be returned to the pH before the carbon dioxide gas is dissolved in a short time. As a result, the pH of the liquid can be controlled not only within the physiological pH range (about 5.0-7.5), but also Avoid the danger of 5-HMF formation and free fatty acids due to the excessive acidity of the liquid. -When the reducing sugar-containing fat milk and an oxygen absorber are packed together in the secondary container, the adverse effects caused by oxygen entering the secondary container can be avoided, so the production of free fatty acids can be more positively suppressed and avoided. Decomposition of this reducing sugar. The above-mentioned fully airtight secondary container can be any container known to have gas barrier properties and container raw materials, including but not limited to polyethylene, polyethylene terephthalate (PET), and polyethylene dicarboxylic acid. (Polyethylene naphthalate, PEN), ethylene vinyl alcohol copolymer (EVOH), polyvinylidene chloride (PVDC), nylon and polyester. The secondary container is preferably a cast material selected from any of the above materials, any thin film or sheet of the material, a thin layered film or sheet of the material 'or a thin film or sheet made of a vapor-deposited layer of silicon or aluminum. More preferably, it is made of a multilayer film. As used in this specification and the scope of the patent application, the term "fully airtight" is an additional reference to the oxygen permeability rate, which generally does not exceed about 1012. This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297). %)

526065 A7 B7 V. Description of the invention (12) ml / m2 / day and preferably not more than about 1 ml / m2 / day. The carbon dioxide gas absorber can be any known carbon dioxide gas absorber, including commercially available products such as "E200", "E400", and "E500" (all manufactured by Mitsubishi Gas Chemical), and there is no particular limitation on the use of such absorbers Mode. In the case of fine powders, the required amount of the powder can be packed in air-permeable pouches; in the case of beads, rods, and other shapes, it can be packed in such bags or used directly. For 700 ml of liquid in a plastic injection container, the amount of carbon dioxide gas absorber should be sufficient to absorb at least 500 ml of carbon dioxide gas. The above-mentioned oxygen absorber can be directly or first packed in a breathable pouch depending on the use mode, and packed with the rubber-coated injection container (primary container), and then packed with a carbon dioxide gas absorber in a secondary container. As for the 700 ml of liquid in the primary container, the amount of oxygen absorber should be sufficient to absorb at least 200 ml of oxygen. The above-mentioned carbon dioxide gas absorber and oxygen absorber need not be installed separately, as long as they are sealed in the space between the primary and secondary containers and separated from the primary container. For example, the two absorbers can be mixed and packed in a bag. Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) The reducing sugar-containing fat milk of the present invention can be obtained in the above manner, and the fat milk can be used in the same way as traditional injection products, such as opening The contents of the secondary packaging are used alone in the primary packaging, or mixed with other substances such as prepared amino acids, and the injection solution or mixture is given to the patient by intravenous injection to complete the desired nutrition supply. Brief description of the drawing 13 This paper size applies to the Chinese National Standard (CNS) A4 specification (210X 297 mm) 526065 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (14) Fat milk and oxygen absorber respectively Sealed with a carbon dioxide gas absorber in an airtight outer bag. After removing the internal air with nitrogen, store the bag at 60 ° C, 75% humidity. After completion and seven and fourteen days after completion, the content of free fatty acids was measured. To quantify the above free fatty acid content, each test sample extracted with n-heptane can be titrated with a 0.011 N aqueous sodium hydroxide solution. Titration with thymol blue as an indicator under a stream of nitrogen, the end point of the titration when it changes from red to blue. The results are shown in Fig. 1. (1) in this case represents the fat milk containing reducing sugar in this case, and (2) represents the comparative fat milk. As can be seen from Figure 1, compared with the comparative fat milk, the fat milk in this case can significantly inhibit the production of free fatty acids. Example 2 Distilled water for injection was added to purified soybean oil, purified egg yolk lecithin, glucose, and organic acid (succinic acid) according to the following formula, and mixed with a TK homomixer, and the mixture was placed at 75 ° C Rough emulsification was performed for 30 minutes, and then a Manton-Gaulin homogenizer (400 kg / cni 2, 10 times) was used to provide an emulsion. The emulsion was adjusted to 10 liters, and the pH was adjusted to 6.0 with a 1N sodium hydroxide solution. .. Formula Purified Soybean Oil Purified Egg Yolk Lecithin (12% in Soybean Oil) Glucose 1 Succinic acid 44.4 g / 1 5.33 g / 1 1 14.3 g / 1 0.2 g / ί (Please read the Please fill in this page again for your attention}-order 15 paper size applicable to China National Standard (CNS) A4 specification (210X297 mm)

526065 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 ______B7 _______ V. Description of the Invention (15) Sodium hydroxide (pH control agent) qs Distilled water for injection qs The space above the emulsion preparation tank is pressurized with carbon dioxide gas to make the pH of the emulsion Is 5.2, and then supply a mixed gas with a partial pressure of carbon dioxide (C02: N2 = 45: 5 5) to fill the tank for ventilation, which helps the above pH 値 balance. The emulsion is packed in an injection bag under these conditions. And the same mixed gas as mentioned above is used for filling and ventilating, and sterilizing in a sterilization kettle at 100 ° C for 40 minutes to provide the reducing sugar-containing fat emulsion of this case in an injection dose. Test Example 2 The reducing sugar fat milk prepared in Example 2 was stored at 60 ° C and 75% humidity for 14 days, and the degree of discoloration was observed. 'In this observation, the appearance of the sample can be generally seen. At the same time, the aqueous layer obtained by ultrafiltration centrifugation (Kub ota 〇de 1 KR -1 8 0 A) of the injection sample was measured at 450 with Shimadzu UV-160. Transmittance in nm (T%). At the same time, the pH 値 and free fatty acid (FFA) content of the sample (meq / 1) and the amount of 5-hydroxymethyl-2-furfural (5-HMF) which is a representative decomposition product of reducing sugar (ppm) ) Can be measured by titration and liquid chromatography. For the sake of reference, the same test was performed on the control group sample prepared in Example 2 but omitting the dissolution of carbon dioxide, that is, the preparation tank and the bag were fully vented and completely filled with nitrogen. The test results of each injection after preparation and storage for seven days and fourteen days are shown in Table 1 below. ’16 This paper size applies to China National Standard (CNS) A4 (210X297 mm)

526065 A7 B7 V. Description of the invention (16 samples) ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 5-HMF 0.3 1 1.55 3.93 Appearance is slightly discolored and discolored T% 98.7 96.7 94.3 Control group sample pH 5.52 5.28 5.12 n_i 11 ----: nn _J .......... 1 ^ .1 ϋ (Please (Read the precautions on the back before filling this page) FFA 0.55 1.27 2: 4 5 5-HMF 0.29 3.11 8.04 It can be clearly inferred from the high light transmittance in Table 1 above that the reducing sugar-containing fat milk in this case can significantly inhibit 5 -The formation of HMF and other decomposition products of glucose, so it has a satisfactory quality of a relatively low degree of coloring. It can also be deduced that the formation of sour glucose decomposition products can be minimized. Therefore, although the pH of the fat milk in this case will be affected by Remove the dissolved carbon dioxide and return to the pimple before sterilization, but it can prevent the emulsion from falling into the acidic range over time, and also avoid the formation of free fatty acids during storage. Example 3 Distilled water for injection Add the purified soybean oil, purified egg yolk lecithin, glucose, and organic acid (succinic acid) according to the following formula and mix them with a TK homomixer. The mixture is placed at 75 ° C for 30 minutes to be crude. Emulsion, the crude emulsion was passed through a Manton-Gaiilin, and the paper size was 17 and the paper size was in accordance with China National Standard (CNS) A4 (210X297 mm).

Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs

Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 526065 A7 B7 V. Description of the Invention (18) The results are shown in Table 2. The pH value before injection and the carbon dioxide content in the bag were not as shown in Table 2. Table 2 also shows comparative product I in the same way as above but excluding “E500” (only “AgelessZH200” is packaged with the injection bag), and the air in the preparation tank is removed during sterilization and the injection bag has only nitrogen (no carbon dioxide is used) ) And the results of Comparative Product II excluding "E500" but "Ageless ZH200". Table 2 Samples before sterilization 4 days after 7 days and 18 days after 18 days ) 45.0 27.5 7.47 7.19 5.86 Comparative product II pH 5.20 5.59-5.58 5.58 C02 component (%) 45.0 0.16 0.02 0.02 As can be seen from Table 2, in the injection product in this case, the carbon dioxide gas was almost completely removed after ten days and the pH of the injection solution The tritium rise is close to the original tritium, thus inhibiting the formation of free fatty acids. 19 This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) ^ ------ Order ----- (Please read the precautions on the back before filling this page)

Claims (1)

526065 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs A8 B8 C8 D8 6. Scope of patent application (a) Carbon dioxide gas is dissolved in the fat emulsion composition; and ⑼ When the carbon dioxide gas is dissolved therein, it is subjected to a high-temperature sterilization method Bactericidal; wherein, the reducing sugar-containing fat milk composition includes: (1)-oil-in-water fat milk, which contains _ fat L5_2G w / v% and-emulsifier 3 mg / g; (2) at least Contains-reducing sugar 5_5Gw / v%, which is selected from-one of glucose, one fructose and one maltose; and ^ (3)-succinic acid, 'wherein the impurity and the succinyl series are included in the The water phase towel of Lin milk, the pH of the fat milk is adjusted between pH 5.0 and pH 7.5. 10. The sterilization method according to item 9 of the scope of the patent application, wherein the pH of the fat emulsion composition after the carbon dioxide is dissolved therein is pH 4 to 6.5. It is proposed to apply the sterilization method described in item 9 or ίο, wherein the fat emulsion composition is dissolved before and after sterilization with monooxy carbon? The value of 11 ranges from pH 5 to 75. 12. A method for double-packing a fat milk composition product containing reducing sugar, the method comprising: (1) packaging the fat-containing milk composition containing reducing sugar in a multi-compartment breathable and flexible na injection container; / Sterilize the container containing the miscellaneous fat emulsion composition obtained by (a); and (ii) sterilize the container and the oxygen absorber obtained in step g, and further-step on an air-impermeable exterior In a container; wherein, the fat milk composition containing reducing sugar comprises: ⑴ an oil-in-water fat milk, which contains-fat L5-20 w / v% and an emulsifier 3-30 mg / g ; (2) It contains at least one reducing sugar 5-50w / v%, which is selected from one of _glucose, one fructose and one maltose; and one (3)-No. acid, this paper size applies Chinese National Standard (CNS) A4 size (21〇χ 297 mm) (Please read the precautions on the back before filling this page) 526065, the scope of the application for patent Where the reducing sugar and the succinate series are included in the ㈣ ρΗ value adjusted between ρΗ5._ρΗ75. The preparation method of the fat-containing packaging device-double packaging method of the fat milk composition product containing reducing sugar, the method comprises the following steps: packing material, sugar, and glutinate; The container and the carbon dioxide absorber are in an external container; "." In the milk, the fat milk composition containing reducing sugar comprises: ⑴ an oil-in-water fat milk which contains-fat L5 / v% and -milk-300 mg / g; (2) to = containing-reducing sugar 5_5Gw / v%, which is selected from one of -glucose, -fructose and maltose; and (1 (3)-amber The acid, sugar and sugar are contained in the heterogeneous water, and the pH of the milk is adjusted between pH 5.0 and pH 7.5. The method according to item 13 of line 14 ′ = 2, in which a human-oxygen absorption_ plastic injection trough and the carbon dioxide gas absorber can be additionally packed in the secondary container. 15.—A fat emulsion medical liquid product containing reducing sugar, comprising: (mf peak-containing prefecture __ threat material, silk sugar sugar gift composition, containing: 〇)-oil-in-water fat emulsion, which Contains—Fat 15.2 () w / V% and 30-300 mg / g; (2) Contain at least one 5-5 50 w / v%, which is selected from one of glucose, fructose and maltose And (3) succinic acid, in which the silky_glassy_flour is contained in the water phase towel of the trace milk, and the paper size of the fat milk applies the CNS A4 specification (21Q x 297) )-526065 Printed by A8, B8, C8, D8, Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 6. The scope of the patent application is adjusted between pH 5.0 and pH 7.5. (b) — Multi-compartment breathable and flexible plastic injection container for packaging the medical fluid and a carbon dioxide gas dissolved in the medical fluid; (c) A carbon dioxide gas absorber for absorbing sterilized The carbon dioxide gas dissolved in the medical liquid; and (d)-a secondary container that is impermeable to oxygen, and is used to package the items in (a) to (c). 16. The fat emulsion medical liquid product according to item 15 of the scope of the patent application, the items in (b) must be sterilized before being packaged in the secondary container with the carbon dioxide gas absorber. · This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) (Please read the precautions on the back before filling this page)