TWI698181B - Chewing gum containing multi-unit active carriers - Google Patents

Abstract

A chewing gum containing various multi-unit active carriers is provided. The chewing gum comprises a main body and an outer shell surrounding the main body. Plural active carriers are distributed in the main body, the shell, or both of the chewing gum. The active carriers are used to carry various active substances having bioactivity.

Description

Chewing gum containing multiple active carriers

The present invention relates to the structure of a chewing gum and its preparation method, in particular to the structure of a chewing gum containing active substances and its preparation method.

There are many benefits to chewing gum. Chewing gum regularly can increase saliva secretion, thereby better cleaning the mouth and teeth, reducing the formation of dental plaque, which is very beneficial to periodontal health. In addition, the jaw bone, masseter muscles and teeth can be fully exercised during repeated bite movements, which can avoid the deterioration of masticatory ability caused by aging or disease. In addition, because "chewing" gives the teeth and jaw cells the physical strength, the body's ability to absorb daily food is improved. In addition, because the action of chewing can drive the satiety center, it can prevent overeating and obesity.

Since chewing gum has many benefits, if some active substances can be added to chewing gum, it can make use of chewing gum at the same time. Chewing gum releases active substances, and then further absorbs these active substances through the mouth, which will allow the chewing gum to provide users with more physical and psychological benefits.

Therefore, one aspect of the present invention is to provide a chewing gum containing multiple units of active carriers. The chewing gum includes a chewing gum main body, a chewing gum shell, a plurality of active carriers and at least one active substance. The main material of the chewing gum is mainly edible rubber. The chewing gum shell covers the main body of the chewing gum, and the material of the chewing gum shell is mainly a flavoring agent. The active carriers are distributed in the chewing gum body, the chewing gum shell or a combination thereof. The active substance is distributed in the active carrier, and the active substance is a solid or liquid substance with biological activity.

According to an embodiment of the present invention, the active carriers include microparticles, microspheres, liposomes, sponge mitochondria, drop pills, or any combination of the above.

According to another embodiment of the present invention, at least a part of the active carriers has a coating.

According to another embodiment of the present invention, a polymer is further included in the coating of the active carriers, and the polymer forms mucus in the saliva.

According to another embodiment of the present invention, it further includes an absorption enhancer located in the chewing gum body, the chewing gum shell, the active carriers, or any combination thereof.

According to another embodiment of the present invention, it further includes an acid-base buffer located in the chewing gum body, the chewing gum shell, and the active carriers Or any combination of the above.

According to another embodiment of the present invention, it further includes a viscous substance in the active carrier.

According to still another embodiment of the present invention, wherein the active substance includes a central appetite suppressant.

The above-mentioned summary of the invention aims to provide a simplified summary of the present disclosure, so that readers have a basic understanding of the present disclosure. This summary is not a complete summary of the present disclosure, and its intention is not to point out important/key elements of the embodiments of the present invention or to define the scope of the present invention. After referring to the following embodiments, those skilled in the art to which the present invention belongs can easily understand the basic spirit and other purposes of the present invention, as well as the technical means and implementation aspects of the present invention.

100‧‧‧Chewing gum

102‧‧‧Chewing gum body

104‧‧‧Gum Shell

106‧‧‧Active carrier

In order to make the following and other objectives, features, advantages and embodiments of the present invention more comprehensible, the description of the attached drawings is as follows: Figure 1 is a chewing gum containing multiple active carriers according to an embodiment of the present invention Schematic diagram of the cross-sectional structure of the active carrier system for carrying various active substances.

As mentioned earlier, chewing gum has many benefits. If the active ingredients can be added to the chewing gum, they will be released during the chewing process The active substance is in the saliva and then acts locally on the oral cavity, or is further absorbed by the oral mucosa (including cheek mucosa, sublingual mucosa and oral vestibule). Absorption of active substances from the oral mucosa has the following advantages. For example, it can have an effect (Onset) within 5 minutes, and can use a smaller dosage to achieve the effective concentration in the blood and the highest blood concentration, without passing through the liver. The first metabolism of the small intestine and the small intestine enters the systemic circulation to produce pharmacological effects. It can be deactivated without the decomposition and digestion of gastric acid and gastrointestinal digestive enzymes, and can be transported and circulated directly through the superior vena cava system such as the jugular vein after absorption. To the heart, brain, lungs, skin and other tissues.

At present, the most common one is adding active ingredients that have a bactericidal or cooling sensation in the chewing gum, and there are also smoking cessation chewing gums added with nicotine. However, in the U.S. industry of guidance, there is no independent and clear definition of the oral disintegration powder dosage form or sublingual absorption dosage form that uses the delivery system to deliver drugs, which leads to the oral absorption of the chewing gum type. The dosage form cannot be widely promoted.

In addition, if the active substance is directly added to the chewing gum, the active substance is easily damaged by the high temperature and pressure of the chewing gum processing process, or may have physical and chemical interactions with other substances, and the active substance loses its activity. Moreover, if the active substance is in a liquid state, it cannot be added to the chewing gum, because it may change the physical state of the chewing gum during the manufacturing process, and the chewing gum cannot be formed.

Based on the above, a mouth containing multiple units of active carrier is provided Chewing gum, where the active carrier system is used to carry various active substances. One of the advantages of the above-mentioned chewing gum is that it can increase the absorption of active substances through the oral mucosa, instead of allowing the active substances to be dissolved in saliva and then swallowed into the gastrointestinal tract to be absorbed by the gastrointestinal tract. In the following description, the exemplary structure of the above-mentioned chewing gum containing multiple active carriers and its exemplary manufacturing method will be introduced. In order to easily understand the embodiments, many technical details will be provided below. Of course, not all embodiments need these technical details. At the same time, some well-known structures or elements will only be drawn in the drawings in a schematic manner to appropriately simplify the content of the drawings.

The structure of chewing gum containing multiple active carriers

Please refer to Figure 1. Figure 1 is a cross-sectional structure diagram of a chewing gum containing multiple active carriers according to an embodiment of the present invention. In Figure 1, the appearance of the chewing gum 100 can be any desired shape, such as a spherical shape, a square shape, or any other desired shape. The structure of the chewing gum 100 includes a chewing gum body 102, a chewing gum shell 104 surrounding the surface of the chewing gum body 102, and a multi-unit active carrier 106 for carrying various active substances. The above-mentioned active carrier 106 can be distributed in the chewing gum body 102, the chewing gum shell 104, or both.

The main material of the chewing gum body 102 is edible rubber. Of course, some food additives can be optionally added to obtain some additional effects. For example, it can be used as a flavoring agent for any available Sweeteners, sour agents, spices and taste stimulants. In addition, absorption enhancers can also be added to increase the oral absorption of the active substance. In addition, a weak acid-type acid-base buffer can also be added to keep the molecules of certain active substances in a molecular state or a free state without net charge (that is, neutral) to help them pass through It penetrates the oral mucosa and is absorbed through intracellular or intercellular routes.

The function of the chewing gum shell 104 described above is mainly to improve the taste of the chewing gum 100 and to improve the storage stability of the chewing gum 100. Therefore, the material of the chewing gum shell 104 is mainly flavoring agents, such as sweeteners, sour agents, flavors and taste stimulants. In addition, an absorption enhancer and a weak acid-type acid-base buffer can also be optionally added to the chewing gum shell 104.

The above-mentioned active carrier 106 contains active substances, which may include any available biologically active chemical substances (such as health foods, nutritional supplements) that are artificially synthesized or extracted from natural substances (microbial fermentation products, microbial transformation products, plant and animal tissues) Or drugs) or biological substances (such as enzymes, organelles or dead bacteria). Therefore, when chewing gum 100, the active carrier 106 can release a high concentration of active substance when it is close to the oral mucosa, thereby increasing the absorption of the active substance by the oral mucosa. In the chewing gum body 102, the addition amount of the active carrier 106 is at most 20 wt%. In the chewing gum shell 104, the addition amount of the active carrier 106 is at most 40 wt%.

The available size of the active carrier 106 is about 0.03~3,000 Micrometer, according to an embodiment, it can be 100 to 1,000 micrometers. Generally, when the diameter of the active carrier 106 is less than 150 microns, the tactile sensation of the mouth and tongue is difficult to detect. When the diameter of the active carrier 106 is less than 450 microns, it is difficult to be bitten by the teeth in a short time during chewing, so a longer chewing time can be used to increase the absorption rate of the oral delivery system, so that the active substance can be released slowly It is slowly absorbed, so it can maintain a stable concentration of active substances in the blood for a long time.

The above-mentioned active substances include central appetite suppressants, which can be, for example, African mango extract or bitter orange extract. The bitter orange extract can also improve metabolism.

In addition, the active carrier 106 may optionally include absorption enhancers, acid-base buffers, macromolecules that can form mucus in saliva, and viscous substances. Among them, macromolecules and viscous substances can increase the residence time of active substances in the oral cavity to increase the oral absorption rate of various active substances. For example, it can increase the high water solubility and high mucosal penetration rate, low water solubility but high mucosal penetration rate and high water solubility but belong to the first, second and third categories of the biopharmaceutical classification system (biopharmaceutical classification system I, II and III). Oral absorption rate of active substances with low mucosal penetration.

Active carrier form

The above-mentioned active carrier 106 can be any carrier that can withstand the temperature and pressure of the chewing gum manufacturing process and is sufficient to protect the active material, for example, it can be a pellet or sponge mitochondria that meets the above conditions. (spongellet), microsphere, dropping pill, liposome or any combination of the above.

The above-mentioned particles are tiny spheres or spheres formed by combining powders or liquids of active substances and excipients. The size of the particles is usually less than 2.5 mm, and they are generally prepared by extrusion spheronization. In addition, the particles can also use the liquid stacking method or the powder stacking method to coat the core particles with multiple layers of materials with different functions, and even the outermost layer can be coated with a layer of coating to increase the active material carried by it. Stability, control the release of active substances contained in it or control its adsorption of foreign substances. The type of the above-mentioned coating can be sugar coating or film coating.

In the case of sugar coating, the main material of sugar coating can be monosaccharides, disaccharides or sugar alcohols, so it can not only improve the taste, but also increase the stability and hardness of the particles.

In terms of film coating, its types can be divided into, for example, time-controlled release type, pH-dependent type, moisture-proof type, elastic compression-resistant type, long-acting type and large intestine release type. The material of the film coating can be, for example, a polymer, or a fatty acid with 5-50 carbons or its esters. Therefore, in addition to increasing the stability of the particles, the film coating can also be controlled to disintegrate in a specific environment, allowing the particles to contact the external environment to release active substances.

For example, when the film coating is elastic and compressive (the material is usually elastic fiber or elastin), it can help active substances with less compressive resistance (such as active proteins and polysaccharides, etc.) to resist the effects of chewing gum. Understand the pressure while still maintaining its activity.

For example, when the film coating is of the moisture-proof type, it can also protect the active substances (such as carnitine, etc.) that are sensitive to moisture and lose their activity, so that they can maintain their activity during the chewing gum manufacturing process and during storage.

For example, when the film coating is of a pH-dependent type, such as an acid-insoluble type, it can protect pH-sensitive active substances so that they can maintain their activity during the chewing gum manufacturing process and during storage.

For example, when the film coating is a time-controlled release type, the release rate of the active substance can also be controlled. For example, a sustained-release dosage form can also reduce the bitter, astringent, fishy and other unpleasant tastes released by the active substance in a unit time. If it is an immediate-release dosage form, the sweet, sour, and scent of the active substance can be released quickly, so that it can compete with the active substance with unpleasant taste in the oral taste. Therefore, using this mechanism can solve most of the natural odors of herbal extracts, food additives and drugs in most active substances.

The above-mentioned sponge mitochondria is a porous linear drug carrier, and its preparation method is generally to mix the active substance and the highly water-soluble substance with an appropriate amount of water and extrude it, then freeze-drying, other available drying methods or Combine different drying methods to form sponge mitochondria with porous structure. Because the sponge mitochondria has a porous structure, it can form a composite structure with various particles, liposomes and microspheres.

The material of the porous matrix of sponge mitochondria is usually cellulose, starch, water-soluble substance or a combination thereof. The above-mentioned cellulose can be, for example, hydroxypropyl methyl cellulose cellulose; HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), microcrystalline cellulose (MCC), or any combination thereof. The aforementioned water-soluble substance may be, for example, an amino acid or sugar alcohol. Because the sponge mitochondria has a porous matrix, it can be used to absorb liquid or solid active substances, such as oily active substances (such as high-dose lutein and zeaxanthin) or fine powder from nanometer to submicron. In this way, the structure of the sponge mitochondria can protect the active substance in liquid or suspended state, so that it will not be lost during the squeezing action of the chewing gum manufacturing process, but can remain in the chewing gum. For the solid active material of fine powder, the structure of sponge mitochondria can maintain its activity after processing and during chewing. The aforementioned sponge mitochondria, like the microparticles, can also have various coatings with different functions to achieve the purpose of increasing the stability of the active substance, controlling the release of the active substance, and controlling the adsorption of foreign substances.

The aforementioned microsphere is a drug carrier that allows the drug to be dispersed in a polymer matrix, and its size is usually from nanometers to micrometers, for example, less than 800 microns. Common polymer matrix materials include starch, albumin, gelatin, chitosan (chitosan), polylactide (PLA), cyclic polylactide (CPL) and so on. The preparation method is usually to dissolve or disperse the active material in a polymer solution, and then use spray drying to form a microsphere solid.

The above-mentioned dripping pill is a mixture of drugs and excipients or After being dispersed into a liquid system, it is dropped into a difficult-to-solution body to form. Therefore, it is also a drug carrier for carrying suitable active substances.

The liposome mentioned above is a spherical vesicle structure which can be used to contain drugs. Liposomes can exist in the pores of sponge mitochondria in liquid form.

In summary, the use of the active carrier 106 to carry the active substance and then apply it to chewing gum has at least the following benefits. First, the release period of the active substance can be increased. For example, when the active substance is made into a powder, the release period is generally less than 5 minutes; if it is made into 1mm diameter particles, its release period is about 7.5~15 minutes; if it is made into 0.45mm diameter particles, its release period About 10-15 minutes.

Secondly, the active carrier 106 can increase the stability of the chemical structure of the active material with unstable chemical structure. For active materials with unstable chemical structure, whether they are active materials sensitive to oxygen, humidity, light, temperature, pressure or other factors, the various properties of the active carrier 106 can be modified in various ways to protect the Various active substances with different characteristics will not lose their activity during the production process and storage of the chewing gum, and will exert its complete effect when chewing the gum.

Furthermore, the active carrier 106 can be used to carry active substances that are not suitable to be put together. For example, the active substances that will undergo a chemical reaction to destroy their activity after contact with each other can be carried separately by different active carriers 106, so that they will not come into contact with each other during the manufacturing process and during storage of the chewing gum, thereby maintaining their Original live Sex, until chewing gum does its full effect.

Additive material

The aforementioned flavoring agent can be any available sweetener, sour agent, flavor, taste stimulant or any combination thereof. The sweetener can be monosaccharides, disaccharides or sugar alcohols, such as isomalt, sorbitol, maltitol syrup, sweetness alcohol, aspartame, acesulfame potassium or any combination thereof. The sour agent can be, for example, citric acid, malic acid, lactic acid, gluconic acid, and the like. The flavors can be, for example, various natural fruit flavors, edible plant flavors, and edible artificial flavors. Taste stimulants include cooling agents and red-inducing agents. The cooling agent may be peppermint, and the red-inducing agent may be ginger powder or its oil extract, chili powder or its oil extract, cinnamon powder, peppermint oil, winter green oil And cinnamon oil.

The above-mentioned absorption enhancers generally include surfactants, fatty acids, alcohol, azone, chitosan, phospholipid liquid oily substances, red agents, piperine, etc. Several kinds. The aforementioned surfactants can be, for example, various available anionic surfactants (such as bile salts) and cationic surfactants, which can promote the penetration of water-soluble and fat-soluble substances into the mucosa. The above-mentioned fatty acids can be, for example, C ₈ -C ₂₀ saturated or unsaturated fatty acids, which can affect the intercellular space and increase the absorption rate of active substances. Alcohol, azone and chitosan can reduce the orderly arrangement of lipid molecules in mucosal cells, and help the penetration of active substances. Phospholipid liquid oily substances (such as lecithin) can increase the mucosal penetration rate of active substances with low water solubility but high permeability in the biopharmaceutical classification system II (biopharmaceutical classification system II). The red-inducing agent can be, for example, ginger powder or its oil extract, chili powder or its oil extract, cinnamon powder, peppermint oil, winter green oil and cinnamon oil, etc., which can increase the blood flow of the mucous membranes and promote the active substances absorb.

The above acid-base buffers can be divided into two types: weak acid type and weak base type. The weak acid type acid-base buffer can be, for example, citric acid, malic acid, tartaric acid, phosphoric acid, lactic acid, gluconic acid, glucuronic acid, vitamin C, acetic acid, or salicylic acid. In addition to controlling the pH of the oral cavity and improving the solubility of weak acid or weak base active substances, weak acid acid-base buffers can also reduce the sensitivity to odors (such as bitterness) and help certain The molecules of the active substance are in an electrically neutral free state, so that they can penetrate the oral mucosa and be absorbed. The weakly basic acid-base buffer includes bicarbonate, such as sodium bicarbonate or potassium bicarbonate. The weak base acid-base buffer can not only be used to control the acid-base value in the oral cavity, but also can stabilize some active substances. If it can produce gas, it can also increase the release rate of active substances. When chewing gum needs to add weak acid and weak base buffers at the same time, the weak acid and weak base types must exist in different positions of the chewing gum. The most common situation is that the weak acid exists in the main body of the chewing gum, the multi-unit active carrier, and the weak base exists in the active carrier.

The above-mentioned polymer that can form mucus in saliva is mainly used to form the coating of the active carrier 106, and its materials include methacrylic acid copolymer and methacrylic acid copolymer. Aminoalkyl methacrylate copolymer (aminoalkyl methacrylate copolymer), methacrylate copolymer (methacrylate copolymer), alkyl methacrylate copolymer (alkyl methacrylate copolymer), hydroxypropyl cellulose (hydroxylpropyl cellulose) cellulose, hydroxypropyl methylcellulose, or any combination thereof. The aforementioned methacrylic acid copolymer can be, for example, poly(methacrylic acid-co-ethyl acrylate) 1:1 [Poly(methacrylic acid-co-ethyl acrylate) 1:1], poly(methacrylic acid-co-ethyl acrylate) 1:1], poly(methacrylic acid-co-ethyl acrylate) 1:1 Methyl methacrylate) 1:1[Poly(methacylic acid-co-methyl methacrylate) 1:1], poly(methacylic acid-co-methyl methacrylate) 1:2[Poly(methacylic acid-co- methyl methacrylate) 1:2] or poly(methyl acrylate-co-methyl methacrylate-co-methacrylic acid) 7:3:1[Poly(methyl acrylate-co-methyl methacrylate-co-methacrylic acid)7 ：3:1]. The above-mentioned coating materials can pass through different processing and coating steps, thereby forming different film coating layers or shell layers.

The above-mentioned sticky substance may be, for example, gelatin, starch, polysaccharide, hydroxypropyl methylcellulose, protein, polypeptide, dead bacteria or any combination thereof. The above-mentioned starch may be corn starch, tapioca starch, yam starch or sweet potato starch, for example. The source of polysaccharides can be, for example, plant extracts, or fermentation by yeast or fungi. The aforementioned protein may be, for example, collagen or glycoprotein.

Preparation method of chewing gum containing multiple active carriers

The preparation method of chewing gum containing multiple units of active carrier is as follows.

First, the step of mixing and stirring is carried out, and the required raw materials (edible rubber, active carrier and other required additives) are uniformly mixed together by stirring. In this step, it is necessary to heat at 80~120℃ to reduce the viscosity of the edible rubber and increase the fluidity to facilitate the mixing and stirring.

Then, the mixed crude product is cut into an appropriate size, and then processed into a desired shape to form the chewing gum body 102 in Figure 1. Next, for example, using a spheronization step, a spherical mass is formed.

Finally, the surface of the chewing gum body 102 is coated with a mixture of hot icing sugar and the required additives to form the chewing gum shell 104 to complete the production of the chewing gum 100.

Example 1: Factors affecting the release time of active substances

In this embodiment, the multi-unit active carrier used is African mango compound particles, and the active substance is African mango extract. African mango is produced from wild mango (African mango, scientific name Irvingia gabonensis) in Cameroon, Africa. The mango seed extract can help regulate physiology, master key metabolic functions, adjust the body from the base, and achieve healthy beauty (US 7537790).

In the test, users were asked to chew (experimental group) or squeeze and muzzle (control group) to record the length of time the sweetness exists in the oral cavity, and also record the frequency of saliva swallowing.

Chewing gum is a round-shaped chewing gum commissioned by Uni-Confectionery. Its overall long diameter is 1.5cm, short diameter is 1.2cm, and the thickness of the chewing gum shell is 0.8mm. Each chewing gum has an average weight of 2.4 grams and contains 200 mg of African mango compound particles (containing 50% by weight of African mango extract), sweeteners (including isomalt, sorbitol, maltitol syrup, sweetness alcohol) , Aspartame, acesulfame potassium), chewing gum, fragrance, soy lecithin, acacia, palm wax, antioxidant (dibutylhydroxytoluene), food yellow pigment No. 4, antioxidant (butyl Hydroxymethoxybenzene). The chewing gum shell is a yellow sugar-coated shell with an average weight of 0.3 grams.

According to statistics, when an adult eats a normal meal, 10 Swallow 50 times in a minute appointment. Adults swallow saliva 37 times per hour when sitting still. When adults speak, they will swallow more frequently. Generally speaking, chewing will increase the secretion of saliva, and the higher the frequency of swallowing the saliva, the shorter the time the active substance can stay in the oral cavity, reducing the oral absorption rate of the active substance.

Comparing the control group (Experimental Examples 1-1 to 1-3) and the experimental group (Experimental Examples 1-4 to 1-6), it can be seen that because the experimental group has chewing action, the amount of saliva secretion will be greater, which can be The higher frequency of saliva swallowing proved it, and the result was that the sweetness of the experimental group was in the oral cavity for a shorter time than the control group. Regardless of whether it is the experimental group or the control group, the higher the frequency of swallowing saliva, the time that the sweetness exists in the oral cavity generally increases.

Example 2: Hunger index before and after eating chewing gum

In this embodiment, the multi-unit active carrier used is African mango compound microparticles or bitter orange compound microparticle chewing gum, and its active substances are African mango extract or bitter orange extract, respectively. The above-mentioned African mango extract is as described in Example 1, and will not be repeated here. The above-mentioned bitter orange extract is extracted from the peel of the immature bitter orange (Citrus aurantium L.), especially the green peel contains the most. The extracted active substances contain norepinephrine-like synephine, citric acid and hesperidine flavonoids. Biologists have found that bitter orange extract (especially furin is norepinephrine-like) is a kind of inhibitory Appetite and satiety, promotion of basal metabolic rate (the related metabolic mechanism includes accelerating energy consumption of body tissues) and adjustment of physiological functions (including the autonomic nervous system) and other functions, in order to achieve the goal of losing weight and maintaining health.

In the test, users were asked to chew (experimental group) or squeeze and muzzle (control group) to record the length of time the sweetness exists in the oral cavity, and also record the frequency of saliva swallowing.

Chewing gum is a round-shaped chewing gum commissioned by Uni-Candy. Its overall long diameter is 1.5cm, short diameter is 1.2cm, and the thickness of the chewing gum shell is 0.8mm. Add about 10-15wt% of fine particles to each chewing gum, which are African mango compound fine particles or bitter orange compound fine particles. Among them, the addition amount of the African mango compound particles per chewing gum is 100mg, and the African mango compound particles contain 50wt% of African mango extract and add mango flavor (Experimental Examples 2-7 to 2-9). The added amount of bitter orange compound particles is 300 mg, and the bitter orange compound particles contain 6 wt% bitter orange extract and coffee flavor is added (Experimental Examples 2-10 to 2-12). In addition, sweeteners (including isomalt, sorbitol, maltitol syrup, sweetness, aspartame, acesulfame potassium), chewing gum, flavors, soy lecithin, arabic Gum, palm wax, antioxidant (dibutylhydroxytoluene), food yellow color No. 4, antioxidant (butylhydroxymethoxybenzene). The chewing gum shell is an orange sugar-coated shell.

In the following experimental examples, experimental examples 2-1 to 2-6 are control groups, and experimental examples 2-7 to 2-12 are experimental groups. The test method of hunger index is a 10-point questionnaire method. The index range from no hungry to very hungry is 1-10 points. The measurement index of the subject directly reflects the current hunger state. The results obtained are listed in Table 2 below.

From the results in Table 2, it can be seen that the control group without active substances (Experimental Examples 2-1 to 2-3), and when the user eats chewing gum by mouth (Experimental Examples 2-4 to 2-6) In the control group, the effect of reducing the hunger index is limited. On the contrary, when the users of the experimental group (Experimental Examples 2-7 to 2-12) eat chewing gum by chewing, the effect of reducing their hunger index is obvious.

Example 3: Comparison of the active substance release effects of different oral release dosage forms

In this example, several different oral release activities are tested The dosage form of the substance is compared with the length of the sustained release time of the active substance in the oral cavity. The active substance used here is vitamin C, so it is to test the length of time the sourness stays in the mouth. Before the test, rinse your mouth with drinking water to maintain sufficient and constant humidity and a relatively constant temperature in the oral cavity. The following describes the dosage forms tested in each experimental example, and the results are listed in Table 3.

In Experimental Example 3-2, the tested dosage form is a chewing gum containing a multi-unit active carrier of vitamin C. After peeling off the sugar coating, the chewing gum is mixed with a multi-unit active carrier containing 200mg of vitamin C particles (containing 115mg of vitamin C), which is made by extrusion spheronization, and extruded with a 1.0mm orifice plate, spheronized at 500rpm, and spheronized at 5wt. % Of curcumin staining.

In Experimental Example 3-2, the tested dosage form was a chewing gum containing vitamin C. After peeling off the sugar coating, the chewing gum is directly mixed with 200mg of vitamin C particles.

In Experimental Example 3-3, the tested dosage form was a sublingual absorption capsule containing vitamin C. The preparation method is to first poke 3 holes on the head and body of No. 3 capsule (gelatin material, produced by Dafeng Company) with a 24 gauge needle (outer diameter 0.67mm) before filling, totaling 6 holes. . Then, about 115 mg of lactose (purchased from Mingtai Company) and about 115 mg of vitamin C (purchased from Jude Company) were filled into the capsule. Because of the good fluidity and formability of the above-mentioned materials, they can be directly used to make Granules, and directly beat the tablets.

In Experimental Example 3-4, the tested dosage form was a sublingual tablet containing vitamin C. This sublingual tablet has a diameter of about 6mm, contains 115mg of lactose and about 115mg of vitamin C. The material is also a direct dosage form.

In Experimental Examples 3-5, the tested dosage form was a lozenge containing vitamin C. This lozenge contains 115mg lactose and 115mg vitamin C, and the material is also a direct dosage form.

In Experimental Examples 3-5, the tested dosage form is an oral disintegrating tablet containing vitamin C. This orally disintegrating tablet contains 100mg lactose, 100mg vitamin C and 30mg disintegrating powder (sodium starch glycolate), and the material is also a straight-on formulation.

^a Dissipate time with sublingual tactile sensory preparation

^b Dissipate time with sublingual tactile sensory preparation

^c about 2 seconds/time

From the results in Table 3, it can be seen that the sublingual absorption capsule (Experimental Example 3-3) can keep vitamin C under the tongue for the longest time. The design of sublingual absorption capsules allows vitamin C to be released through the capsule hole and contained in the sublingual cavity, so that saliva containing active ingredients is not easily swallowed into the gastrointestinal tract, so it has the highest sublingual absorption rate. When vitamin C is mixed directly with the chewing gum material (Experimental Example 3-2) or mixed with the chewing gum material in the form of an active carrier (Experimental Example 3-1), the retention time of the sour taste in the mouth can be as long as the sublingual absorption capsule (Experimental Example 3-3), and better than orally disintegrating tablets (Experimental Example 3-6).

The dissolution rate of sublingual tablets (Experimental Example 3-4), Buccal tablets (Experimental Example 3-5) and Oral Disintegration Tablets (Experimental Example 3-6) is fast, but vitamin C enters the intestines and stomach with saliva swallowing reflex action Therefore, most vitamin C is absorbed through the gastrointestinal tract rather than sublingually.

Example 4: The effect of different dosage forms on the absorption rate of active substances and the time of maintaining effective concentration in blood

In this example, several different oral dosage forms for releasing active substances were tested to compare the absorption rate of the active substances and the length of time the effective concentration in the blood was maintained. The active substance used here is Vitamin B2, so the color of urine can tell how long vitamin B stays in the body.

The preparation method of the multi-unit active carrier of vitamin B2 is as follows. First dissolve vitamin B2 and sucralose in glycerides at 60-70°C. The weight ratio of vitamin B2, sucralose and glycerides is 0.50:0.05:0.45, and the total weight is 500g. After evenly mixing, let the mixture cool quickly to form a thin yellow lump. The obtained yellow flakes are crushed by a pulverizer and passed through a No. 40 sieve to obtain yellow fine powder (containing vitamin B2 yellow fine powder mixed with 50% glycine). After the obtained yellow thin block is crushed by a pulverizer, it is sieved with a No. 40 mesh to obtain a yellow fine powder (the content of vitamin B2 is 50 wt%). Then, the yellow fine powder and glycine are mixed, and the weight ratio of the yellow fine powder and glycine is 3:7. Then use a single-screw extruder (Chongqing Yingge, E50, orifice plate 0.6mm) and add 10wt% distilled water of the total weight of the raw materials, then extrude, place it in a moisture-proof box and dry it in the shade for about 48 hours to form vitamin B2 (15wt%) ) Active carrier (in the form of sponge mitochondria). Then, lactose and 0.5wt% sucralose were added to prepare an active carrier containing vitamin B2 (10.8wt%).

In Experimental Example 4-1, the dosage form used was a chewing gum containing vitamin B2 particles, but the shell was peeled off. The content of vitamin B2 particles is 20wt%, which contains 10.8wt% of vitamin B2.

In Experimental Example 4-2, the dosage form used was a sublingual tablet. The above 230 mg vitamin B2 microparticles (with 25 mg of vitamin B2) were directly injected into a tablet to form a sublingual tablet with a diameter of 7 mm.

In Experimental Example 4-3, the dosage form used is sublingual absorption Type capsule. The preparation method is to first poke 3 holes on the head and body of the No. 3 capsule (gelatin material, produced by Dafeng Company) with a 24 gauge needle (outer diameter 0.67mm), totaling 6 holes. The capsule is then filled with approximately 230 mg of vitamin B2 multi-unit active carrier, which contains 25 mg of vitamin B2.

In Experimental Example 4-4, the dosage form used was a lozenge. Here, 230 mg of vitamin B2 microparticles (with 25 mg of vitamin B2) and 70 mg of lactose are used to make a lozenge with a diameter of 11 mm.

In Experimental Example 4-5, the dosage form used was an orally disintegrating tablet. Here, 230 mg of vitamin B2 microparticles (with 25 mg of vitamin B2), 30 mg of sodium starch glycolate (disintegrating powder) and 40 mg of lactose were made into tablets with a diameter of 10 mm.

The test method is to let the same person drink 300 mL of drinking water at 9 am on five different days, and then take the various oral dosage forms of Vitamin B2 in Experimental Examples 3-1 to 3-5. Then, the urine color was tested at different time points (09:00, 09:15, 09:30, 10:30, 13:00 and 15:00). Urine is compared by the color rendering method. For standard products of the color rendering method, see Table 4. The standard product E is urine at 09:00 when vitamin B2 is not taken, and the standard product A~D are made by adding different amounts of vitamin B2 to the standard product E. Please see Table 5 for the test results.

Generally speaking, if the active substance is absorbed by the oral cavity, it enters the blood circulation faster, because it saves the time to be absorbed in the stomach and intestines. Because the oral absorption method allows the active substance to enter the blood circulation faster, it also allows the active substance to reach the kidney faster, and can Exhaust excess active substances through the kidneys. Relatively speaking, if the oral absorption rate is low, the active substance has to wait until the stomach and intestines to begin to be absorbed and enter the blood circulation, so it also slows to reach the kidneys.

It can be seen from Table 5 that the fastest urine to turn yellow is the sublingual tablet of Experimental Example 4-2. The urine starts to turn yellow 15 minutes after consumption. Then there is the sublingual absorption type capsule containing vitamin B2 active microparticles of Experimental Example 4-3. The urine only starts to turn yellow 15-30 minutes after consumption. Finally, the oral lozenges of Experimental Example 4-4 and the oral disintegrating tablets of Experimental Example 4-5. It takes 90 minutes after eating before the urine begins to turn yellow.

The rate of yellowing of the urine of the chewing gum containing vitamin B2 active microparticles in Experimental Example 4-1 was similar to that of the sublingual absorption capsule containing vitamin B2 active microparticles in Experimental Example 4-3. This result shows that the oral absorption rate of the active substance of the chewing gum containing active particles is at least similar to that of the sublingual absorption type capsules containing active particles.

The time point when the color of urine changes from yellow to colorless is the latest time point of oral tablet in Experimental Example 4-4. The chewing gum containing vitamin B2 active particles in Experimental Example 4-1 is the same as Experimental Example 4-4. The time point of Zhikou lozenges is similar, all 320 minutes after consumption. Show that both have a certain gastrointestinal absorption ratio.

It can be seen from the above disclosure that the active carrier in the chewing gum containing multiple units of active carrier can be used to carry various active substances, which can increase the release period of the active substance and increase the absorption of the active substance through the oral mucosa. Secondly, the active carrier can protect the active substances with different characteristics, so that they can be used in the production process of chewing gum. It will not lose its activity during neutralization and storage. The active carrier can also be used to carry active substances that are not suitable for putting together, while maintaining their original activity.

Although the present invention has been disclosed in the above embodiments, it is not intended to limit the present invention. Anyone familiar with the art can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the protection of the present invention The scope shall be subject to the definition of the attached patent scope.

100‧‧‧Chewing gum

102‧‧‧Chewing gum body

104‧‧‧Gum Shell

106‧‧‧Active carrier

Claims (20)

A chewing gum containing multiple units of active carriers, the chewing gum comprising: a chewing gum body, the material of which is mainly edible rubber; a chewing gum shell, which covers the chewing gum body, and the material of the chewing gum shell is mainly a flavoring agent; and a plurality of porous sponge mitochondria , Distributed in the chewing gum body, the chewing gum shell, or a combination thereof, the porous sponge mitochondria material includes a single amino acid; at least one non-medical active substance is distributed in the porous sponge mitochondria, wherein The active substance is a solid or liquid substance with biological activity; wherein the preparation of the porous sponge mitochondria includes the following steps: after mixing the at least one non-medical active substance with the single amino acid, then adding about 10wt% The water is extruded by a wet granulation method to obtain the porous sponge mitochondria with a particle size of about 0.6 mm. The chewing gum according to claim 1, wherein the material of the porous sponge mitochondria further includes cellulose or starch. The chewing gum according to claim 1, wherein at least a part of the porous sponge mitochondria has a coating. The chewing gum as described in claim 3, further including one The macromolecule is located in the coating of the porous sponge mitochondria, and the macromolecule forms mucus in the saliva to increase the time for the active substance to stay in the oral cavity. The chewing gum according to claim 4, wherein the polymer comprises a copolymer of methacrylic acid, a copolymer of aminoalkyl methacrylate, a copolymer of methacrylate, and a copolymer of alkyl methacrylate Cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, or any combination thereof. The chewing gum according to claim 1, further comprising an absorption enhancer located in the chewing gum body, the chewing gum shell, the porous sponge mitochondria, or any combination of the foregoing. The chewing gum according to claim 6, wherein the absorption enhancer comprises a surfactant, fatty acid, alcohol, azone, chitosan, phospholipid liquid oily substance, red agent and piperine or any combination thereof. The chewing gum according to claim 7, wherein the fatty acid comprises C ₈ -C ₂₀ saturated or unsaturated fatty acid. The chewing gum according to claim 7, wherein the phospholipid liquid oily substance comprises lecithin. The chewing gum according to claim 7, wherein the surfactant includes an anionic surfactant or a cationic surfactant. The chewing gum according to claim 7, wherein the red-inducing agent comprises ginger powder or its oil extract, chili powder or oil extract, cinnamon powder, peppermint oil, winter green oil or cinnamon oil. The chewing gum according to claim 1, further comprising an acid-base buffer in the chewing gum body, the chewing gum shell, the porous sponge mitochondria, or any combination of the above. The chewing gum according to claim 12, wherein the acid-base buffer in the chewing gum body, the chewing gum shell, or any combination thereof includes a weak acid buffer, and the weak acid buffer includes citric acid, malic acid, tartaric acid, and phosphoric acid , Lactic acid, gluconic acid, glucuronic acid, vitamin C, acetic acid or salicylic acid. The chewing gum according to claim 12, wherein the acid-base buffer in the porous sponge mitochondria comprises a weak base buffer, and the weak base buffer comprises bicarbonate. The chewing gum according to claim 1, further comprising a sticky substance located in the mitochondria of the porous sponge. The chewing gum according to claim 15, wherein the viscous substance includes gelatin, starch, polysaccharide, hydroxypropyl methylcellulose, protein, polypeptide, dead bacteria or any combination thereof. The chewing gum according to claim 1, wherein the active substance for non-medical use includes a central appetite suppressant to suppress the appetite of the user. The chewing gum according to claim 17, wherein the central appetite suppressant comprises African mango extract or bitter orange extract. The chewing gum according to claim 1, wherein the active substance for non-medical use includes a metabolism improving agent. The chewing gum according to claim 19, wherein the metabolism improving agent comprises bitter orange extract.

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