Composition for reducing oral sweetness of artificially synthesized disaccharide and improving taste and application thereof

Abstract

The invention discloses a composition for reducing oral sweetness of artificially synthesized disaccharide and improving taste and application of the composition. The composition in the form of oral gel at least comprises the following components in percentage by mass: 30%-70% of lactulose, 0.05%-2% of a gel matrix material and the balance of water. The composition in the form of oral gel can be used for preparing lactulose oral gel. The lactulose oral gel which is fresh and smooth in taste, easy to swallow, free of adhesion to oral mucosa, free of stickiness and low in bleeding rate is obtained by researching the variety and dosage of the gel matrix material.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and specifically relates to a composition for reducing the oral sweetness of artificially synthesized disaccharides and improving the taste, and an application thereof. Background Art

[0002] Lactulose is a synthetic disaccharide, mainly used in the treatment of chronic or habitual constipation and hepatic encephalopathy. It is widely used in clinical practice because of its good laxative effect. At present, the reference preparation is the lactulose oral solution (Dumik) of Abbott Trading (Shanghai) Co., Ltd., with specifications of 15ml:10g and 200ml:133.4g.

[0003] Lactulose itself has a strong sweetness, and its concentration in oral solution is very high. Existing lactulose oral solution does not contain any excipients, and no taste masking technology is used. When taking lactulose oral solution, the lactulose molecules are fully exposed in the mouth, resulting in a strong sweetness and poor taste. After taking it, the oral mucosa is in an irritated state for a long time, and the taste buds are numb and astringent. The [Usage and Dosage] section of its instructions clearly states that "lactulose should be swallowed directly and should not stay in the mouth", which is due to the above-mentioned sweetness considerations. However, in general, it is not easy for patients to follow this precaution; the strong sweetness reduces the patient's medication experience, causing the patient to have poor compliance, and therefore it is difficult for the patient to follow the doctor's advice. There are also examples of taste disorders after long-term use of lactulose oral solution.

[0004] CN112601520A discloses a novel consumable gummy delivery system comprising lactulose and a preparation method thereof, wherein the composition comprises lactulose, a gelling agent, a sweetener, a buffer, a flavoring agent, a coloring agent, an anti-adherent and a preservative, wherein the gelling agent is gelatin, pectin, carrageenan or pectin and carrageenan. The preparation process comprises the steps of mixing, heating, dissolving, stirring, adjusting pH value, casting, cooling, drying, coating, etc. The prescription and the steps of the above method are all relatively complicated. And it claims that the compliance of the patient can be improved, but no detailed description is given for what effect may be achieved. In addition, for the elderly, the younger children and infants, the gummy dosage form has the situation of chewing difficulty, which is not conducive to taking. Summary of the invention

[0005] The present invention aims to provide a composition and its application for reducing the oral sweetness of artificially synthesized disaccharides and improving the taste in view of the deficiencies of the prior art. The composition provided by the present invention can be used to prepare lactulose oral gel. The lactulose oral gel prepared by the present invention is a soft jelly-like gel with a fixed shape. When used for oral administration, it has low sweetness, a refreshing and smooth taste, is easy to swallow, does not adhere to the oral mucosa, has no sticky feeling, and has a low water separation rate.

[0006] The purpose of the present invention is achieved through the following technical solutions:

[0007] The invention provides a composition in the form of an oral gel, which comprises the following components by mass percentage: 30% to 70% of lactulose, 0.05% to 2% of a gel matrix material, and the balance being water.

[0008] The lactulose-containing composition of the present invention is in the form of an oral gel. This gel-like medicine is similar to soft jelly, has a smooth mouthfeel, is soft and easy to swallow, but does not drip. For patients with chewing disorders, the gel can be easily squeezed out of the package, or scooped with a spoon, crushed in the mouth, and can be delivered into the pharyngeal cavity with only a small amount of force. For patients with swallowing disorders, the soft jelly gel can effectively and appropriately mobilize the activity and coordination of the lips, tongue and pharynx, which is conducive to swallowing.

[0009] A preferred embodiment of the present invention is that the oral gel composition comprises the following components by mass percentage: 40% to 60% lactulose, 0.35% to 1% gel matrix material, and the balance is water.

[0010] In the composition of the present invention, the water content is the residual amount of the sum of the mass percentages of lactulose, gel matrix materials and possible other additives, and is used to dissolve the components. Theoretically, the higher the water content, the thinner and softer the jelly-like gel.

[0011] In the composition of the present invention, the minimum amount of the gel matrix material is limited to the amount of the gel that forms a non-flowable gel after cooling and gelling. The higher the content of the gel matrix material, the harder the jelly-like gel. Therefore, the content of the gel matrix material selected in the present invention is 0.05% to 2%, preferably 0.35% to 1%.

[0012] Preferably, the gel matrix material is one or more of agar, locust bean gum, xanthan gum, carrageenan, pectin, gelatin or sodium alginate.

[0013] The invention uses gel matrix materials such as agar, locust bean gum, xanthan gum, carrageenan, pectin, gelatin, sodium alginate and the like as gelling agents, selects the type and amount of the gelling agent, and is expected to make lactulose into a soft jelly-like oral gel with moderate sweetness and good taste. The three-dimensional network structure formed by the gel matrix can bind lactulose molecules, reduce the spreading, diffusion and contact area of ​​lactulose molecules in the oral cavity, thereby alleviating the sweetness, reducing the stimulation of the sweetness on the taste buds and the influence on the taste habits.

[0014] The present invention adds lactulose to a gel matrix material to form a soft jelly-like gel, thereby suppressing the sweetness of lactulose. Although it seems that there are many kinds of gel matrix materials to choose from, the selection range of a gel matrix material for a soft jelly-like gel containing lactulose is limited in view of its appearance and taste masking effect, the compatibility of the gel material with lactulose, and the production feasibility. For example, the gel formed by using agar alone is brittle and rough; the gel formed by gellan gum is rich in juice, but it has a melt-in-the-mouth mouthfeel and poor water retention capacity, which is not conducive to reducing the sweetness of lactulose. Sodium alginate forms a gel by cross-linking reaction with calcium ions, but controlling the gelling time has always been a technical difficulty, which is not conducive to amplifying production control. In addition, the reducing sugars contained in the lactulose raw material medicine include galactose, lactose, fructose, etc., and gelatin and reducing sugars may undergo Maillard reaction at high temperature to produce browning. In addition, high methoxyl pectin can cause degradation of lactulose when the pH value is less than 3.5.

[0015] Jelly-like gels with different ingredients and proportions may seep water onto the surface of the gel over time, causing dehydration and shrinkage. When this phenomenon becomes obvious, the separated liquid diffuses into the mouth, pharynx, etc. when taking the medicine, allowing the patient to clearly feel the taste of the drug ingredients, which is a strong sweet taste in this product; the separated liquid may also enter the trachea and cause choking. If the type and amount of gel matrix material are not selected properly, a hard jelly with a harder texture and reduced compliance may be obtained, or a soft jelly-like gel with a fixed shape may not be formed, or the viscosity may be high during the production process, or it may be difficult to control the viscosity and difficult to carry out industrial production. Therefore, it is necessary to select the appropriate type and amount of gel matrix material.

[0016] Since the single use of gel matrix materials has some disadvantages in some aspects, for example, pure agar gel is quite brittle and has low fracture strength. When locust bean gum is added, its elasticity and fracture strength are greatly improved. The composite gel has high fracture strength and better mechanical properties. Xanthan gum and agar have similar double helix structures, and a small amount of xanthan gum molecules can form a three-dimensional network structure with agar molecules. Compared with pure agar gel, the composite gel has no tendency of syneresis or a reduced tendency of syneresis. Gelatin alone has poor elasticity, carrageenan has poor water retention, and sodium alginate may not be able to form a gel without adding calcium ions. When they are compounded in a certain proportion, the disadvantages of using them alone will be improved. For example, konjac glucomannan mixed with xanthan gum, carrageenan, etc. has a strong gel synergistic effect, which can maximize the advantages. Therefore, the research on the formula and properties of various composite gels is becoming more and more extensive.

[0017] Further preferably, the gel matrix material is a compound of agar and locust bean gum, or a compound of agar and xanthan gum, or a compound of agar, locust bean gum and xanthan gum. The use of the above compounded gel matrix material can obtain moderate sweetness and low water separation rate.

[0018] Furthermore, the mass percentage of the agar in the gel matrix material is 60% to 80%.

[0019] The present invention also provides an application of the above-mentioned oral gel composition in the preparation of lactulose oral gel.

[0020] The invention prepares the lactulose oral gel by encapsulating lactulose in a gel matrix material, thereby meeting the objectives of low sweetness, good taste and easy swallowing.

[0021] The present invention also provides a lactulose oral gel, which is prepared from the above-mentioned oral gel composition. The lactulose oral gel of the present invention is in the form of a soft jelly-like gel, has a sweet taste ranging from almost tasteless to moderately sweet (light sweetness), has a refreshing and smooth taste, is easy to swallow, does not adhere to the oral mucosa, and has no sticky feeling.

[0022] The lactulose oral gel prepared by the present invention is a soft jelly-like gel, which has a reduced sweetness when taken orally, a smooth mouthfeel and is easy to swallow. In the lactulose oral gel of the present invention, since lactulose is dissolved and wrapped in the three-dimensional network structure of the gel matrix, the gel enters the pharynx in the form of small lumps after simple chewing in the oral cavity, and the taste buds do not contact a large number of lactulose molecules, which can significantly reduce the sweetness. In addition, since the jelly-like gel does not adhere to the oral cavity, pharynx and other parts, it is not easy to feel the sweetness and the aftertaste of the sweetness. In addition, the soft jelly-like gel in the present invention has good water retention and low water separation rate. As time goes by, water slowly seeps out of the gel matrix, which is a normal phenomenon of the jelly-like gel, and the ideal water separation rate is 5% or less. Since lactulose is dissolved in the separated water, when the water separation rate is large, the oral cavity, pharynx and other parts are easy to feel a strong sweetness, which may lead to a reduction in taking compliance; there is also a risk of losing the separated water when taking, which may lead to a reduction in clinical efficacy.

[0023] In addition to the gel matrix material, the lactulose oral gel of the present invention may also contain other auxiliary materials as additives for the oral gel, such as pH regulators, flavoring agents, preservatives, etc. Adding the above additives to the composition in conventional amounts in the art does not affect the properties and sweetness of the product.

[0024] Based on the gel matrix material described above, a pH adjuster can be added to give the lactulose oral gel a sour taste and a sweet and sour taste, thereby improving the palatability of the oral gel and making it easier to take. However, due to changes in pH, some pH adjusters may cause lactulose to decompose.

[0025] Furthermore, the pH adjuster is citric acid, anhydrous citric acid, sodium citrate, calcium citrate, sodium dihydrogen citrate, glucose-δ lactone, succinic acid, acetic acid, tartaric acid, potassium tartrate, sodium tartrate, calcium hydroxide, sodium calcium hydroxide, sodium bicarbonate, lactic acid, calcium lactate, anhydrous sodium monohydrogen phosphate, dl-malic acid, hydrated sodium hydrogen phosphate, dipotassium phosphate, etc.

[0026] Furthermore, the pH regulator is citric acid or anhydrous citric acid. Citric acid also has the function of regulating the pH of the product and acting as a stabilizer, and is often used in combination with sodium citrate.

[0027] In addition to the gel matrix material and pH adjuster described above, flavoring agents commonly used in the food and pharmaceutical fields may be added to season and enhance the flavor.

[0028] Furthermore, the flavoring agent is a water-soluble flavor, strawberry flavor, cherry flavor, orange flavor, pineapple flavor, apple flavor, mint flavor, lemon flavor, chocolate flavor, etc. and a combination thereof.

[0029] In addition to the gel matrix material, pH adjuster and flavoring agent described above, preservatives commonly used in the food and pharmaceutical fields may be added to prevent the lactulose oral gel from spoiling.

[0030] Furthermore, the preservative is benzoic acid, sodium benzoate, sorbic acid, potassium sorbate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, etc.

[0031] The prescription composition and dosage of lactulose oral gel are optimized to make it have a more beautiful appearance, suitable gel strength, refreshing taste, smooth and easy to swallow, no adhesion to the oral mucosa, no sticky feeling, and low water precipitation rate. The lactulose oral gel of the present invention is suitable for all people, especially for the elderly, infants and children.

[0032] The present invention also provides a method for preparing the lactulose oral gel, comprising the following steps:

[0033] (1) adding part or all of the gel matrix material into water, heating at 90°C to 100°C for at least 0.5 h to allow the gel matrix material to fully swell to form a gel matrix solution, and keeping the solution at 50°C to 70°C for later use;

[0034] (2) adding lactulose to the gel matrix solution obtained in step (1) and stirring thoroughly to dissolve;

[0035] (3) adding one or more of a pH adjuster, a flavoring agent or a preservative to the gel matrix solution containing lactulose obtained in step (2), and stirring thoroughly to dissolve;

[0036] (4) Remove bubbles under heat preservation condition;

[0037] (5) filling and cooling to obtain the lactulose oral gel;

[0038] In terms of mass percentage, the lactulose oral gel contains 30% to 70% lactulose, 0.05% to 2% gel matrix material, 0 to 1% of the total mass of pH regulator, flavoring agent and preservative, and the balance is water.

[0039] Preferably, the total weight of the pH adjuster and preservative is 0.10% to 0.80%.

[0040] In step (1), different types or amounts of gel matrix materials can be added at different temperatures. Some compositions containing gel matrix materials need to be partially added with lactulose in this step to avoid possible salting out.

[0041] Beneficial effects:

[0042] (1) The present invention provides a lactulose soft jelly-like oral gel with a weak sweetness, good taste and wide applicability.

[0043] (2) The present invention uses 0.35 wt% to 1 wt% of agar, xanthan gum and / or locust bean gum as gel matrix materials, which are swollen in water under certain process conditions to dissolve lactulose in the gel matrix to form a soft jelly-like gel, thereby reducing the sweetness of lactulose when taken orally.

[0044] (3) The present invention studies the type and amount of gel matrix material to obtain a lactulose oral gel that has a refreshing and smooth taste, is easy to swallow, does not adhere to the oral mucosa, has no sticky feeling, and has a low water separation rate.

[0045] (4) The present invention adds a pH regulator to make the lactulose oral gel have a lighter sour-sweet taste, thereby improving palatability and enhancing patient compliance. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1 This is a physical picture of the appearance of the lactulose oral gel prepared in Example 4 of the present invention.

[0047] Figure 2This is the result of amplitude scanning of the lactulose oral gel prepared in Example 4 using a TA HR10 rotational rheometer in the present invention. DETAILED DESCRIPTION

[0048] The technical solution of the present invention is described in detail below through specific embodiments, but the protection scope of the present invention is not limited to the embodiments.

[0049] Example 1 Preparation of lactulose oral gel

[0050] (1) Add 48.9 g of water to a liquid preparation tank, add 0.3 g of agar and 0.15 g of xanthan gum as gel matrix materials while stirring, heat at 90° C. for 1 hour to allow the solution to swell fully to form a gel matrix solution, and keep the solution at 60° C. for later use;

[0051] (2) Add 50 g of lactulose powder to the gel matrix solution and stir to dissolve; then add 0.3 g of citric acid, 0.25 g of sodium citrate, and 0.1 g of potassium sorbate and stir to dissolve;

[0052] (3) Ultrasonic bubble removal under heat preservation condition;

[0053] (4) Filling and cooling to obtain lactulose oral gel.

[0054] Under natural light, the appearance of the lactulose oral gel prepared in Example was visually evaluated as a slightly yellowish, transparent, soft jelly-like gel with a fixed shape.

[0055] Example 2 Preparation of lactulose oral gel

[0056] (1) Add 48.8 g of water to a liquid preparation tank, add 0.4 g of agar and 0.15 g of xanthan gum as gel matrix materials while stirring, heat at 100° C. for 0.5 hour to fully swell the solution to form a gel matrix solution, and keep the solution at 70° C. for later use;

[0057] (2) Add 50 g of lactulose powder to the gel matrix solution and stir to dissolve; then add 0.3 g of citric acid, 0.25 g of sodium citrate, and 0.1 g of potassium sorbate and stir to dissolve;

[0058] (3) Ultrasonic bubble removal under heat preservation condition;

[0059] (4) Filling and cooling to obtain lactulose oral gel.

[0060] Under natural light, the appearance of the lactulose oral gel prepared in Example was visually evaluated as a slightly yellowish, transparent, soft jelly-like gel with a fixed shape.

[0061] Example 3 Preparation of lactulose oral gel

[0062] (1) Add 58.92 g of water to a liquid preparation tank, add 0.38 g of agar and 0.1 g of xanthan gum as gel matrix materials while stirring, heat at 100° C. for 0.5 hour to fully swell the gel matrix solution, and keep at 70° C. for later use;

[0063] (2) Add 40 g of lactulose powder to the gel matrix solution and stir to dissolve; then add 0.25 g of citric acid, 0.25 g of sodium citrate, and 0.1 g of potassium sorbate and stir to dissolve;

[0064] (3) Ultrasonic bubble removal under heat preservation condition;

[0065] (4) Filling and cooling to obtain lactulose oral gel.

[0066] Under natural light, the appearance of the lactulose oral gel prepared in Example was visually evaluated as a slightly yellowish, transparent, soft jelly-like gel with a fixed shape.

[0067] Example 4 Preparation of Lactulose Oral Gel

[0068] (1) Add 49.02 g of water to a liquid preparation tank, add 0.38 g of agar and 0.1 g of xanthan gum as gel matrix materials while stirring, heat at 100° C. for 0.5 hour to fully swell the solution to form a gel matrix solution, and keep the solution at 70° C. for later use;

[0069] (2) Add 50 g of lactulose powder to the gel matrix solution and stir to dissolve; then add 0.2 g of citric acid, 0.2 g of sodium citrate, and 0.1 g of potassium sorbate and stir to dissolve;

[0070] (3) Ultrasonic bubble removal under heat preservation condition;

[0071] (4) Filling and cooling to obtain lactulose oral gel.

[0072] Under natural light, the appearance of the lactulose oral gel prepared in Example was visually evaluated as a slightly yellowish, transparent, soft jelly-like gel with a fixed shape. Figure 1 .

[0073] Example 5 Preparation of Lactulose Oral Gel

[0074] (1) Add 38.92 g of water to a liquid preparation tank, add 0.38 g of gel matrix material agar and 0.1 g of xanthan gum while stirring, heat at 90° C. for 0.5 hour to fully swell the solution to form a gel matrix solution, and keep at 50° C. for later use;

[0075] (2) Add 60 g of lactulose powder to the gel matrix solution and stir to dissolve; then add 0.25 g of citric acid, 0.25 g of sodium citrate, and 0.1 g of potassium sorbate and stir to dissolve;

[0076] (3) Ultrasonic bubble removal under heat preservation condition;

[0077] (4) Filling and cooling to obtain lactulose oral gel.

[0078] Under natural light, the appearance of the lactulose oral gel prepared in Example was visually evaluated as a slightly yellowish, transparent, soft jelly-like gel with a fixed shape.

[0079] Example 6 Preparation of Lactulose Oral Gel

[0080] (1) Add 48.9 g of water to a liquid preparation tank, add 0.35 g of gel matrix material agar and 0.1 g of xanthan gum while stirring, heat at 90° C. for 0.5 hour to fully swell and form a gel matrix solution, and keep warm at 50° C. for later use;

[0081] (2) Add 50 g of lactulose powder to the gel matrix solution and stir to dissolve; then add 0.3 g of citric acid, 0.25 g of sodium citrate, and 0.1 g of potassium sorbate and stir to dissolve;

[0082] (3) Ultrasonic bubble removal under heat preservation condition;

[0083] (4) Filling and cooling to obtain lactulose oral gel.

[0084] Under natural light, the appearance of the lactulose oral gel prepared in Example was visually evaluated as a slightly yellowish, transparent, soft jelly-like gel with a fixed shape.

[0085] Example 7 Preparation of Lactulose Oral Gel

[0086] (1) Add 48.8 g of water to a liquid preparation tank, add 0.35 g of gel matrix material agar and 0.2 g of xanthan gum while stirring, heat at 90° C. for 0.5 hour to fully swell and form a gel matrix solution, and keep warm at 50° C. for later use;

[0087] (2) Add 50 g of lactulose powder to the gel matrix solution and stir to dissolve; then add 0.3 g of citric acid, 0.25 g of sodium citrate, and 0.1 g of potassium sorbate and stir to dissolve;

[0088] (3) Ultrasonic bubble removal under heat preservation condition;

[0089] (4) Filling and cooling to obtain lactulose oral gel.

[0090] Under natural light, the appearance of the lactulose oral gel prepared in Example was visually evaluated as a slightly yellowish, transparent, soft jelly-like gel with a fixed shape.

[0091] Example 8 Preparation of Lactulose Oral Gel

[0092] (1) Add 49.4 g of water to a liquid preparation tank, add 0.35 g of gel matrix material agar and 0.15 g of xanthan gum while stirring, heat at 95° C. for 0.5 hour to fully swell the solution to form a gel matrix solution, and keep the solution at 50° C. for later use;

[0093] (2) adding 50 g of lactulose powder to the gel matrix solution and stirring to dissolve; then adding 0.1 g of potassium sorbate and stirring to dissolve;

[0094] (3) Ultrasonic bubble removal under heat preservation condition;

[0095] (4) Filling and cooling to obtain lactulose oral gel.

[0096] Under natural light, the appearance of the lactulose oral gel prepared in Example was visually evaluated as a slightly yellowish, transparent, soft jelly-like gel with a fixed shape.

[0097] Example 9 Preparation of Lactulose Oral Gel

[0098] (1) Add 49.2 g of water to a liquid preparation tank, add 0.35 g of agar and 0.15 g of xanthan gum as gel matrix materials while stirring, heat at 90° C. for 0.5 hour to fully swell the solution to form a gel matrix solution, and keep the solution at 50° C. for later use;

[0099] (2) Add 50 g of lactulose powder to the gel matrix solution and stir to dissolve; then add 0.1 g of citric acid, 0.1 g of sodium citrate, and 0.1 g of potassium sorbate and stir to dissolve;

[0100] (3) Ultrasonic bubble removal under heat preservation condition;

[0101] (4) Filling and cooling to obtain lactulose oral gel.

[0102] Under natural light, the appearance of the lactulose oral gel prepared in Example was visually evaluated as a slightly yellowish, transparent, soft jelly-like gel with a fixed shape.

[0103] Example 10 Preparation of lactulose oral gel

[0104] (1) Add 48.86 g of water to a liquid preparation tank, add 0.38 g of gel matrix material agar and 0.11 g of locust bean gum while stirring, heat at 90° C. for 0.5 hour to fully swell and form a gel matrix solution, and keep warm at 60° C. for later use;

[0105] (2) Add 50 g of lactulose powder to the gel matrix solution and stir to dissolve; then add 0.3 g of citric acid, 0.25 g of sodium citrate, and 0.1 g of potassium sorbate and stir to dissolve;

[0106] (3) Ultrasonic bubble removal under heat preservation condition;

[0107] (4) Filling and cooling to obtain lactulose oral gel.

[0108] Under natural light, the appearance of the lactulose oral gel prepared in Example was visually evaluated as a slightly yellowish, transparent, soft jelly-like gel with a fixed shape.

[0109] Example 11 Preparation of Lactulose Oral Gel

[0110] (1) Add 49.02 g of water to a liquid preparation tank, add 0.38 g of gel matrix material agar, 0.05 g of xanthan gum, and 0.05 g of locust bean gum while stirring, heat at 90° C. for 0.5 hour to fully swell and form a gel matrix solution, and keep warm at 60° C. for later use;

[0111] (2) Add 50 g of lactulose powder to the gel matrix solution and stir to dissolve; then add 0.2 g of citric acid, 0.2 g of sodium citrate, and 0.1 g of potassium sorbate and stir to dissolve;

[0112] (3) Ultrasonic bubble removal under heat preservation condition;

[0113] (4) Filling and cooling to obtain lactulose oral gel.

[0114] Under natural light, the appearance of the lactulose oral gel prepared in Example was visually evaluated as a slightly yellowish, transparent, soft jelly-like gel with a fixed shape.

[0115] Comparative Example 1

[0116] (1) Add 49.1 g of water to a liquid preparation tank, add 0.1 g of gel matrix material agar and 0.15 g of xanthan gum while stirring, heat at 90° C. for 0.5 hour to fully swell and form a gel matrix solution, and keep warm at 60° C. for later use;

[0117] (2) Add 50 g of lactulose powder to the gel matrix solution and stir to dissolve; then add 0.3 g of citric acid, 0.25 g of sodium citrate, and 0.1 g of potassium sorbate and stir to dissolve;

[0118] (3) Ultrasonic bubble removal under heat preservation condition.

[0119] (4) Filling and cooling.

[0120] Under natural light, the appearance of the lactulose oral gel prepared in Comparative Example 1 was visually evaluated as follows: the gel was slightly yellow and had no fixed shape and was easily dissolved in water.

[0121] Comparative Example 2

[0122] (1) Add 49 g of water to a liquid preparation tank, add 0.2 g of agar and 0.15 g of xanthan gum as gel matrix materials while stirring, heat at 90° C. for 0.5 hour to fully swell the solution to form a gel matrix solution, and keep the solution at 60° C. for later use;

[0123] (2) Add 50 g of lactulose powder to the gel matrix solution and stir to dissolve; then add 0.3 g of citric acid, 0.25 g of sodium citrate, and 0.1 g of potassium sorbate and stir to dissolve;

[0124] (3) Ultrasonic bubble removal under heat preservation condition.

[0125] (4) Filling and cooling.

[0126] Under natural light, the appearance of the lactulose oral gel prepared in Comparative Example 2 was visually evaluated as follows: a slightly yellowish, transparent, soft jelly-like gel with a fixed shape and a soft texture.

[0127] Comparative Example 3

[0128] (1) Add 49 g of water to a liquid preparation tank, add 0.35 g of agar, a gel matrix material, while stirring, heat at 90° C. for 0.5 hour to allow it to swell fully to form a gel matrix solution, and keep it at 60° C. for later use;

[0129] (2) Add 50 g of lactulose powder to the gel matrix solution and stir to dissolve; then add 0.3 g of citric acid, 0.25 g of sodium citrate, and 0.1 g of potassium sorbate and stir to dissolve;

[0130] (3) Ultrasonic bubble removal under heat preservation condition.

[0131] (4) Filling and cooling.

[0132] Under natural light, the appearance of the lactulose oral gel prepared in Comparative Example 3 was visually evaluated as follows: a slightly yellowish, transparent, jelly-like gel with a fixed shape and a hard and brittle texture.

[0133] Comparative Example 4

[0134] (1) Add 48.7 g of water to a liquid preparation tank, add 0.1 g of agar and 0.6 g of carrageenan as gel matrix materials while stirring, heat at 90° C. for 0.5 hour to allow the solution to swell fully to form a gel matrix solution, and keep the solution at 60° C. for later use;

[0135] (2) Add 50 g of lactulose powder to the gel matrix solution and stir to dissolve; then add 0.25 g of citric acid, 0.25 g of sodium citrate, and 0.1 g of potassium sorbate and stir to dissolve;

[0136] (3) Ultrasonic bubble removal under heat preservation condition.

[0137] (4) Filling and cooling.

[0138] Under natural light, the appearance of the lactulose oral gel prepared in Comparative Example 4 was visually evaluated as follows: a slightly yellowish, transparent, soft jelly-like gel with a fixed shape and a chewy texture.

[0139] Comparative Example 5

[0140] (1) Add 47.65 g of water to a liquid preparation tank, add 1.25 g of carrageenan and 0.5 g of pectin as gel matrix materials while stirring, heat at 100° C. for 0.5 hour to allow the solution to swell fully to form a gel matrix solution, and keep the solution at 60° C. for later use;

[0141] (2) Add 50 g of lactulose powder to the gel matrix solution and stir to dissolve; then add 0.25 g of citric acid, 0.25 g of sodium citrate, and 0.1 g of potassium sorbate and stir to dissolve;

[0142] (3) Ultrasonic bubble removal under heat preservation condition.

[0143] (4) Filling and cooling.

[0144] Under natural light, the appearance of the lactulose oral gel prepared in Comparative Example 5 was visually evaluated as follows: a slightly yellowish, transparent, soft jelly-like gel with a fixed shape and a soft texture.

[0145] Comparative Example 6

[0146] (1) Add 46.15 g of water to a liquid preparation tank, add 0.25 g of xanthan gum and 3 g of gelatin as gel matrix materials while stirring, and heat at 60° C. for 0.5 hour to allow the mixture to swell fully to form a gel matrix solution;

[0147] (2) Add 50 g of lactulose powder to the gel matrix solution and stir to dissolve; then add 0.25 g of citric acid, 0.25 g of sodium citrate, and 0.1 g of potassium sorbate and stir to dissolve;

[0148] (3) Ultrasonic bubble removal under heat preservation condition.

[0149] (4) Filling and cooling.

[0150] Under natural light, the appearance of the lactulose oral gel prepared in Comparative Example 6 was visually evaluated: the gel was yellow, transparent, and had a fixed shape. It was viscous, had a certain fluidity, and was easily deformed.

[0151] Comparative Example 7

[0152] (1) Add 46.15 g of water to a liquid preparation tank, add 0.25 g of locust bean gum, 2 g of gelatin, and 1 g of sodium alginate as gel matrix materials while stirring, and heat at 60° C. for 0.5 hour to allow the mixture to swell fully to form a gel matrix solution;

[0153] (2) Add 50 g of lactulose powder to the gel matrix solution and stir to dissolve; then add 0.25 g of citric acid, 0.25 g of sodium citrate, and 0.1 g of potassium sorbate and stir to dissolve;

[0154] (3) Ultrasonic bubble removal under heat preservation condition.

[0155] (4) Filling and cooling.

[0156] Under natural light, the appearance of the lactulose oral gel prepared in Comparative Example 7 was visually evaluated as follows: a yellow, transparent solid with a fixed shape, and a hard and relatively sticky texture.

[0157] Example 12 Taste Evaluation

[0158] Evaluation method of the mouthfeel of lactulose oral gel: adult oral tasting method

[0159] Ask different subjects to taste the samples according to the taste evaluation steps in Table 1, and evaluate the sweetness and taste of each batch of gel according to the evaluation criteria in Table 2. The number of subjects is ≥ 6, and the average of the subjects' sweetness and taste evaluation is calculated. The higher the score, the closer it is to the ideal setting.

[0160] Table 1. Taste evaluation steps of lactulose oral gel

[0161] Serial number step 1 Rinse mouth with drinking water 2 Take an appropriate amount of sample, chew it in your mouth, and stay for about 3 seconds to taste the flavor 3 Conduct a preliminary assessment of the samples, and do not record the taste evaluation level. 4 Repeat step 2 5 Make final assessment of the samples and record 6 After 2 minutes, record the aftertaste rating and describe the taste

[0162] Table 2 Corresponding standards for taste evaluation grades

[0163]

[0164]

[0165] Taste description: The lactulose oral gels prepared in Examples 1 to 11 have relatively low sweetness, with only a light sweet taste; they have a refreshing and smooth taste, are easy to swallow, do not adhere to the oral mucosa, and have no sticky feeling.

[0166] The taste scores are shown in Table 3:

[0167] Table 3 Mean sweetness ratings of Examples 1 to 11

[0168] Example Sweetness 1 3.0 2 3.7 3 3.8 4 3.2 5 3.2 6 3.7 7 3.0 8 3.0 9 3.1 10 3.5 11 3.6

[0169] It can be seen from the scoring results that the sweetness scores of Examples 1 to 11 are all 3.0 and above.

[0170] The sweetness and taste of each batch of gel prepared from the marketed product Dumic and Comparative Examples 1 to 7 were evaluated using the above method. The results are shown in Table 4.

[0171] Table 4 Mean sweetness score and taste record of comparative examples

[0172]

[0173]

[0174] The gel matrix of Comparative Examples 1 and 2 is a combination of agar + xanthan gum. Compared with the combination of agar + xanthan gum in the embodiment, the mass percentage of agar in the gel matrix material is only 40% and 57%, and the amount of the gel matrix material is low, the gel formation is not good, resulting in an unsatisfactory taste masking effect on lactulose. Therefore, when compounded with xanthan gum or locust bean gum, the agar content is preferably between 60% and 80%.

[0175] The gel matrix of Comparative Example 3 is only agar, which has a good taste masking effect and a light sweet taste after molding. However, the gel of agar alone has a brittle taste and has a hard feel compared with the combination of agar + xanthan gum, agar + locust bean gum, agar + xanthan gum and locust bean gum in the examples.

[0176] The gel matrix of Comparative Example 4 is carrageenan + agar, which has a good taste masking effect and a chewy texture after molding. However, after being placed for about 10 days, a large amount of water is separated out, and a strong sweet taste appears.

[0177] The gel matrices of Comparative Examples 5 to 7 do not contain agar, and the obtained gels all have a sticky feel after being formed.

[0178] The taste masking effect of Comparative Examples 5 and 6 was poor, and there was a distinct strong sweet taste.

[0179] The taste masking effect of Comparative Example 7 is good, and the gel has no obvious taste, but the mouth or throat is sticky when chewing and swallowing.

[0180] Example 13 Water Separation Rate

[0181] Determination method of water separation rate:

[0182] Take two pieces of filter paper, place them on a scale, and peel them. Take a pack of gel, cut open one side of the package, pour all the gel on the filter paper (make the gel lie flat), weigh the filter paper and gel together (W1, which is the weight of the gel), let it stand for about 3 minutes, gently scrape off the gel with a medicine spoon, and weigh again (W2, which is the weight of the precipitated water).

[0183] The water separation rate was calculated according to the following formula (unit: g):

[0184] Water separation rate = W2 / W1×100%

[0185] The water separation rate results of the gels prepared in the examples and comparative examples and Dumik are shown in Table 5.

[0186] Table 5 Water separation rate results

[0187]

[0188]

[0189] It can be seen from the experimental results that the water separation rates of Examples 1 to 11 are all relatively low. Among the comparative examples, except for Comparative Examples 2 and 5, the water separation rates of the other comparative examples (1, 3, 4) are all relatively high.

[0190] In general, all aspects of Examples 1 to 11 performed well, while Comparative Examples 1 to 7 always had one or more indicators that failed to meet the standards, among which the sweetness of Comparative Examples 1, 2, 5, and 6 was relatively strong and did not have a taste masking effect. Although the appearance and sweetness scores of Comparative Examples 3 and 4 were both excellent, the gel had poor water retention, and there was a risk of losing the separated water when taking it, which may lead to a reduction in clinical efficacy.

[0191] In summary, preferably, agar and locust bean gum are compounded, or agar and xanthan gum are compounded, or agar, locust bean gum and xanthan gum are compounded, the mass percentage of agar in the gel matrix material is 60% to 80%, and the amount of the gel matrix material is preferably 0.35% to 1%.

[0192] Example 14 Gel Strength

[0193] The gel prepared in Example 4 was subjected to amplitude scanning using a TA HR10 rotational rheometer.

[0194] The specific setting parameters are as follows:

[0195] Use 25mm parallel plate, Oscillation Amplitude mode:

[0196] Temperature: 25℃

[0197] Equilibration time: 180.0s Waiting temperature: On

[0198] Angular frequency: 10.0rad / s

[0199] Stress: 1.0e-7MPa to 1.0e-3MPa

[0200] Sampling points per order of magnitude: 10

[0201] Results Figure 2 .

[0202] It can be seen from the figure that the gel prepared in Example 4 shows brittle fracture, and the characteristic peak of the loss modulus G" curve indicates that micro cracks are formed before the material structure decomposes, and the intersection point of G"=G' and the G" maximum value converge at the same point. In region 1, before the maximum value of the curve is reached, only micro cracks appear, and here G'>G" (solid state) is still present. In region 2, the region exceeds the maximum value, and micro cracks develop throughout the sample, reaching the intersection point of G"=G'; thereafter, G">G' (fluid state).

[0203] The storage modulus G' curve drops sharply at γ = 20% (i.e., the limit of the linear viscoelastic zone), and the sample transitions from a static state to a flowing state more rapidly, indicating that brittle fracture characteristics have occurred. This means that under the action of shear, it will break into larger pieces rather than break into small pieces, which will not cause the oral cavity to come into contact with more lactulose molecules. Beyond the linear viscoelastic zone, the G' function curve continues to drop (rather than a cliff-like drop), and the sample transitions from a static state to a flowing state more gently, indicating that the superlattice structure is gradually decomposing and the gel has a smooth characteristic.

[0204] As described above, although the present invention has been shown and described with reference to specific preferred embodiments, it should not be construed as limiting the present invention itself. Various changes in form and details may be made without departing from the spirit and scope of the present invention as defined in the appended claims.

Claims

1. A composition in the form of an oral gel, characterized in that Calculated by mass percentage, it at least comprises the following components: 30% to 70% lactulose, 0.05% to 2% gel matrix material, and the balance is water.

2. The composition in the form of an oral gel according to claim 1, characterized in that Calculated by mass percentage, it at least comprises the following components: 40% to 60% lactulose, 0.35% to 1% gel matrix material, and the balance being water.

3. The composition in the form of an oral gel according to claim 1, characterized in that The gel matrix material is one or more of agar, locust bean gum, xanthan gum, carrageenan, pectin, gelatin or sodium alginate.

4. The composition in the form of an oral gel according to claim 3, characterized in that The gel matrix material is a compound of agar and locust bean gum, or a compound of agar and xanthan gum, or a compound of agar, locust bean gum and xanthan gum.

5. The composition in the form of an oral gel according to claim 4, characterized in that The mass percentage of the agar in the gel matrix material is 60% to 80%.

6. Use of the oral gel composition according to any one of claims 1 to 5 in the preparation of lactulose oral gel.

7. A lactulose oral gel, characterized in that: The oral gel composition is prepared from the oral gel composition according to any one of claims 1 to 5.

8. A method for preparing the lactulose oral gel according to claim 7, characterized in that: The following steps are involved: (1) adding part or all of the gel matrix material into water, heating at 90°C to 100°C for at least 0.5 h to allow the gel matrix material to fully swell to form a gel matrix solution, and keeping the solution at 50°C to 70°C for later use; (2) adding lactulose to the gel matrix solution obtained in step (1) and stirring thoroughly to dissolve; (3) adding one or more of a pH adjuster, a flavoring agent or a preservative to the gel matrix solution containing lactulose obtained in step (2), and stirring thoroughly to dissolve; (4) Remove bubbles under heat preservation condition; (5) filling and cooling to obtain the lactulose oral gel; In terms of mass percentage, the lactulose oral gel comprises 30% to 70% lactulose, 0.05% to 2% gel matrix material, 0 to 1% of the total mass of pH regulator, flavoring agent and preservative, and the balance is water.

9. The preparation method according to claim 8, characterized in that: The total weight of the pH regulator and preservative is 0.10% to 0.80%.

10. The lactulose oral gel according to claim 7, characterized in that: The lactulose oral gel is used for the elderly, adults, children and infants.

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