TW201703639A - 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 units of active carrier

The invention relates to a structure of a chewing gum and a preparation method thereof, in particular to a structure of a chewing gum containing an active substance and a preparation method thereof.

Chewing gum has many benefits. Chewing gum often increases saliva secretion, which in turn improves the mouth and teeth and reduces the formation of plaque, which is very beneficial for periodontal health. Moreover, when the occlusion action is repeated, the jaw bone, the masseter muscle and the teeth can be fully exercised to avoid deterioration of the chewing ability caused by aging or disease. In addition, the ability of the body to absorb daily food is enhanced by the physical strength of "chewing" to the teeth and the jaw cells. In addition, since the chewing action can drive the satiety center, it can prevent overeating and prevent obesity.

Since chewing gum has many advantages, if you can add some active substances to the chewing gum, let the chewing gum be used at the same time. Chewing gum releases the active substance, and further absorption of these active substances through the mouth will allow the chewing gum to provide more physiological and psychological benefits to the user.

Accordingly, one aspect of the invention is to provide a chewing gum comprising a plurality of active carriers. The chewing gum comprises a chewing gum body, a chewing gum shell, a plurality of active carriers, and at least one active substance. The material of the chewing gum body is mainly edible rubber. The chewing gum shell coats the chewing gum body, and the material of the chewing gum shell is primarily a flavoring agent. The active carriers are distributed within 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 biologically active solid or liquid substance.

According to an embodiment of the invention, the active carriers comprise microparticles, microspheres, liposomes, sponge granules, dropping pills or any combination thereof.

According to another embodiment of the invention, at least a portion of the active carriers have a coating.

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

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

According to another embodiment of the present invention, an acid-base buffer is further included in the chewing gum body, the chewing gum shell, and the active carrier. Or any combination of the above.

According to still another embodiment of the present invention, a viscous substance is further included in the active carrier.

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

The Summary of the Invention is intended to provide a simplified summary of the present disclosure in order to provide a basic understanding of the disclosure. This Summary is not an extensive overview of the disclosure, and is not intended to be an The basic spirit and other objects of the present invention, as well as the technical means and implementation aspects of the present invention, can be readily understood by those of ordinary skill in the art.

100‧‧‧ chewing gum

102‧‧‧ chewing gum body

104‧‧‧ Chewing gum shell

106‧‧‧Active carrier

The following and other objects, features, advantages and embodiments of the present invention will become more <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; Schematic cross-sectional structure in which the active carrier is used to carry a variety of different active substances.

As mentioned earlier, chewing gum has many benefits. If the active ingredient can be added to the chewing gum, it will be released during chewing. The active substance is in the oral cavity, and then locally acts on the oral cavity, or is further absorbed by the oral mucosa (including the buccal mucosa, the sublingual mucosa and the oral vestibule). Absorption of the active substance by the oral mucosa has the following advantages, for example, an onset can be produced within 5 minutes, and a small dose can be used to achieve an effective concentration in the blood and a maximum blood concentration, without passing through the liver. And the first metabolism of the small intestine enters the systemic circulation to produce pharmacological effects, which 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 tissues such as the heart, brain, lungs, and skin.

At present, the most common one is to add active ingredients with bactericidal or refreshing sensation to the chewing gum, in addition to smoking nicotine added to nicotine. However, in the US industry's industry of guidance, there is no independent and clear definition of an oral disintegration or sublingual absorption of a drug delivered by a delivery system, resulting in oral absorption of the chewing gum form. 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 destroyed by the high temperature and high pressure of the chewing gum processing process, or may interact with other substances to cause physical and chemical interaction, and the active substance is inactivated. 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 process, and the chewing gum cannot be formed.

According to the above, a mouth containing a multi-unit active carrier is provided Chewing gum, wherein the active carrier is used to carry a variety of different active substances. One of the benefits of the above chewing gum is that it can increase the absorption of the active substance through the oral mucosa, rather than allowing the active substance to dissolve in the saliva, and then swallowed into the gastrointestinal tract and absorbed by the gastrointestinal tract. In the following description, the above-described exemplary structure containing a multi-unit active carrier chewing gum and its exemplified manufacturing method will be described. In order to facilitate an understanding of the described embodiments, a number of technical details are provided below. Of course, not all embodiments require these technical details. In the meantime, some well-known structures or elements are only shown in the drawings in a schematic manner to appropriately simplify the drawing.

Structure containing multi-unit active carrier chewing gum

Please refer to FIG. 1. FIG. 1 is a schematic cross-sectional view showing a chewing gum containing a multi-unit active carrier according to an embodiment of the present invention. In Figure 1, the chewing gum 100 can be of any desired shape, such as a sphere, a cube, or any other desired shape. The structure of chewing gum 100 includes a chewing gum body 102, a chewing gum shell 104 enclosing the surface of the chewing gum body 102, and a multi-unit active carrier 106 for carrying various different active substances. The active carrier 106 described above can be distributed within the chewing gum body 102, the chewing gum shell 104, or both.

The main material of the above-mentioned chewing gum body 102 is edible rubber, and it is of course also possible to selectively add some food additives to obtain some additional effects. For example, it can be used as any flavoring agent. Sweeteners, sour agents, flavors and taste stimulants. In addition, an absorption enhancer may also be added to increase the amount of oral absorption of the active substance. In addition, a weak acid type acid-base buffer may be added to allow molecules of certain active substances to be in a molecular state or a free state without a net charge (ie, electrically neutral) to facilitate their wearing. Through the oral mucosa, it is absorbed via intracellular or intercellular pathways.

The above-described chewing gum shell 104 functions mainly to improve the taste of the chewing gum 100 and to improve the storage stability of the chewing gum 100. Accordingly, the material of the chewing gum shell 104 is primarily a flavoring agent such as a sweetener, a sour agent, a flavoring, and a taste stimulating agent. Further, an absorption enhancer and a weak acid type acid-base buffer may be optionally added to the chewing gum shell 104.

The above active carrier 106 contains an active substance, which may comprise any available biologically active chemical substance (such as health food, nutritional supplement) which is artificially synthesized or extracted from natural substances (microbial fermentation products, microbial conversion products, plant and animal tissues). Or drugs) or biological substances (such as enzymes, organelles or dead bacteria). Therefore, when the chewing gum 100 is chewed, the active carrier 106 can release a high concentration of the active substance in the case of being close to the oral mucosa, thereby increasing the absorption amount of the active substance by the oral mucosa. In the chewing gum body 102, the active carrier 106 is added in an amount of up to 20% by weight. In the chewing gum shell 104, the active carrier 106 is added in an amount of up to 40% by weight.

The available size of the active carrier 106 is approximately 0.03~3,000 Micron, according to one embodiment, may be from 100 to 1,000 microns. Generally, when the diameter of the active carrier 106 is less than 150 microns, the touch of the mouth and tongue is difficult to detect. When the diameter of the active carrier 106 is less than 450 micrometers, it is difficult to be bitten by a tooth in a short time when chewing, so that a longer chewing time can be used to increase the absorption rate of the oral delivery system, so that the active substance can be slowly released. It is slowly absorbed, so the stable concentration of the active substance in the blood can be maintained for a long period of time.

The above active substances include central type appetite suppressants, which may be, for example, African mango extract or bitter orange extract, wherein the bitter orange extract may also improve metabolism.

In addition, the active carrier 106 may optionally further comprise an absorption enhancer, an acid-base buffer, a macromolecule capable of forming a mucus in saliva, and a viscous substance. Among them, the polymer and the viscous substance can increase the residence time of the active substance 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 permeability, low water solubility but high mucosal penetration rate and high water solubility of the biopharmaceutical classification system I, II and III, respectively. Oral absorption rate of active substance with low mucosal penetration rate.

Active carrier form

The above 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, pellets or sponge granules which can meet the above conditions. (spongellet), microsphere, dropping pill, liposome, or any combination of the above.

The microparticles described above are microspheres or spheroids formed by combining a powder or a liquid of an active substance with excipients, usually having a size of less than 2.5 mm, and are generally prepared by extrusion spheronization. In addition, the microparticles may also use a liquid lamination method or a powder lamination method to coat a plurality of layers of different functions on the core microparticles, and even a coating layer may be further coated on the outermost layer to increase the active substance carried by the microparticles. Stability, control of the release of its active substances or control of its adsorption of foreign substances. The type of the above coating may be a sugar coating or a film coating.

In the case of sugar coating, the main material of the sugar coating may be, for example, a monosaccharide, a disaccharide or a sugar alcohol, so that not only the taste can be improved, but also the stability and hardness of the microparticles can be increased.

In the case of a film coat, the types thereof can be, for example, a time-controlled release type, a pH-dependent type, a moisture-proof type, an elastic compression type, a long-acting type, and a large-intestine release type. The material of the film coat may be, for example, a polymer or a fatty acid having 5 to 50 carbons or an ester thereof. Therefore, in addition to increasing the stability of the particles, it is also possible to control the film coat to disintegrate under a specific environment, allowing the particles to contact the external environment and release the active material.

For example, when the film coat is elastic compression type (the material is usually elastic fiber or elastin), it can help the less compressive active substances (such as active protein and polysaccharide, etc.) to resist the formation of chewing gum. Understand the pressure while still maintaining its activity.

For example, when the film coat is of a moisture-proof type, it is also possible to protect an active substance (e.g., carnitine, etc.) which is sensitive to moisture and inactivated, so that its activity can be maintained during the manufacturing process and storage of the chewing gum.

For example, when the film coat is pH dependent, such as an acid insoluble type, the pH sensitive active substance can be protected to maintain its activity during the chewing gum manufacturing process and storage.

For example, when the film coat is of a time controlled release type, the release rate of the active material can also be controlled. For example, the sustained release dosage form can also reduce the unpleasant taste of bitterness, astringency, astringency and the like released by the active substance per unit time. In the case of an immediate release dosage form, the sweetness, sourness and a pleasant taste of the active substance can be released relatively quickly, competing with the active substance having an unpleasant taste to compete with the taste of the mouth. Therefore, the use of this machine can solve the natural odor of herbal extracts, food additives and drugs in most active substances.

The above sponge granule is a porous linear drug carrier, which is generally prepared by mixing an active substance with a water-soluble substance and an appropriate amount of water and extruding it, followed by lyophilization, other available drying methods or Different drying methods are combined to form sponge mitochondria having a porous structure. Since the sponge mitochondria have a porous structure, a composite structure can be formed with various fine particles, microlipids, and microspheres.

The material of the porous matrix of sponge mitochondria is typically cellulose, starch, water soluble materials or combinations thereof. The above cellulose may be, for example, hydroxypropyl methyl cellulose. Cellulose; HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), microcrystalline cellulose (MCC), or any combination thereof. The above water-soluble substance may be, for example, an amino acid or a sugar alcohol. Since the sponge granules have a porous matrix, they can be used to absorb active substances in a liquid or solid state, such as oily active substances (such as high doses of lutein and zeaxanthin) or nanometer to submicron fine powder. Thus, for liquid or suspended active materials, the structure of the sponge mitochondria can be protected so that it is not lost during the squeezing action of the chewing gum manufacturing process and can be retained in the chewing gum. For finely divided solid active materials, the structure of the sponge mitochondria maintains its activity during processing and chewing. The above sponge granules, like the microparticles, may also have various coatings of different functions in order to increase the stability of the active substance, control the release of the active substance, and control the adsorption of foreign substances.

The microspheres described above are pharmaceutical carriers which disperse the drug in a polymeric matrix and are typically of the order of nanometers to micrometers, for example less than 800 microns. Common polymer matrix materials include starch, albumin, gelatin, chitosan, polylactide (PLA), and cyclic polylactide (CPL). The preparation method is generally to dissolve or disperse the active substance in the polymer solution, and then form a microsphere solid by spray drying.

The above dropping pills are obtained by uniformly mixing the drug with the excipient or After being dispersed into a liquid system, it is then dropped into a difficult solution to form. Therefore, it is also a pharmaceutical carrier for carrying a suitable active substance.

The above-mentioned liposome is a spherical vesicle structure which can be used for containing a drug inside. The liposome can be present in the form of a liquid in the pores of the sponge granule.

As described above, the use of the active carrier 106 to carry the active substance and thus to the chewing gum has at least the following advantages. First, the release period of the active substance can be increased. For example, when the active material is used as a powder, the release period is generally less than 5 minutes; if the diameter is 1 mm, the release period is about 7.5 to 15 minutes; if the diameter is 0.45 mm, the release period is It is about 10~15 minutes.

Second, the active carrier 106 can increase the chemical structural stability of the active material having an unstable chemical structure. For an active substance which is unstable in chemical structure, whether it is an active substance sensitive to oxygen, moisture, light, temperature, pressure or other factors, various characteristics of the active carrier 106 can be modified in various ways to protect The active substances of various characteristics make them not lose their activity during the production process of the chewing gum and during storage, and exert their complete effects when chewing gum.

Again, the active carrier 106 can be used to carry active materials that are not suitable for placement together. For example, active substances that undergo a chemical reaction to destroy their activity after contact with each other can be carried by different active carriers 106, so that they can be kept out of contact with each other during the production of the chewing gum and during storage. Original life Sex, until the chewing gum is used to its full effect.

Additive material

The flavoring agents described above can be any useful sweetener, sour, flavor, taste stimulant or any combination thereof. Wherein the sweetener may be a monosaccharide, a disaccharide or a sugar alcohol, such as isomalt, sorbitol, maltitol syrup, sweet ol, aspartame, acesulfame potassium or any combination thereof. The sour agent may be, for example, citric acid, malic acid, lactic acid, gluconic acid or the like. The flavors can be, for example, various natural fruit flavors, edible plant flavors, and edible artificial flavors. The taste stimulating agent includes a cooling agent and a red-lighting agent, wherein the cooling agent is, for example, mint, and the red-lighting agent may be ginger powder or an oil extract thereof, paprika powder or an oil extract thereof, cinnamon powder, peppermint oil, winter green oil And cinnamon oil and so on.

The absorption enhancer is substantially composed of a surfactant, a fatty acid, an alcohol, an azone, a chitosan, a phospholipid liquid oily substance, a red-lighting agent, and a piperine. Several. The above surfactants can be, for example, various usable anionic surfactants (such as bile salts) and cationic surfactants, which promote the penetration of water-soluble and fat-soluble substances into the mucosa. The above fatty acid may be, for example, a C ₈ -C ₂₀ saturated or unsaturated fatty acid which affects the intercellular space and increases the absorption rate of the active substance. Alcohol, azone and chitosan can reduce the order of lipid molecules in mucosal cells and contribute to the penetration of active substances. Phospholipid liquid oils such as lecithin increase the mucosal penetration of low water soluble but highly penetrating actives of the biopharmaceutical classification system II. The red-lighting agent can be, for example, ginger powder or an oil extract thereof, paprika powder or an oil extract thereof, cinnamon powder, peppermint oil, winter green oil and cinnamon oil, etc., which can increase the blood flow of the mucosa and promote the active substance. absorb.

The above acid-base buffers can be classified into two types: weak acid type and weak base type. The weak acid type acid-base buffer may 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 increasing the solubility of weak acid or weak base actives, the weak acid acid-base buffer can also reduce the taste sensitivity to odors (such as bitterness) and assist certain The molecules of the active substance are in an electrically neutral free state so that they penetrate the oral mucosa and are absorbed. The weak base type acid-base buffer includes a hydrogencarbonate such as sodium hydrogencarbonate or potassium hydrogencarbonate. In addition to being used to control the pH value in the oral cavity, the weak base type acid-base buffer can also stabilize some active substances, and if it can produce gas, it can also increase the release rate of the active substance. When the chewing gum needs to be added with both weak acid and weak base buffers, the weak acid type and the weak base type must be present in different positions of the chewing gum. The most common case is the presence of a weak acid in the chewing gum body, a multi-unit active carrier, and a weak base present in the active carrier.

The above-mentioned polymer capable of forming a mucus in saliva is mainly used for forming a coating of the active carrier 106, and the material thereof includes a methacrylic acid copolymer and a methacrylic acid. Aminoalkyl methacrylate copolymer, methacrylate copolymer, alkyl methacrylate copolymer, hydroxypropyl cellulose Cellulose), hydroxypropyl methylcellulose or any combination thereof. The above copolymer of methacrylic acid may be, for example, poly(methacrylic acid-co-ethyl acrylate) 1:1 [poly(methacrylic acid-co-ethyl acrylate) 1:1], poly(methacrylic acid-co- Methyl methacrylate) 1:1 [Poly (methacylic acid-co-methyl methacrylate) 1:1], poly(methacrylic acid-co-methyl methacrylate) 1:2 [Poly (methacylic acid-co- Methyl methacrylate): 2:2] 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 coating materials can be passed through different processing coating steps to form different film coating layers or outer skin layers.

The above-mentioned viscous substance may be, for example, gelatin, starch, polysaccharide, hydroxypropylmethylcellulose, protein, polypeptide, dead bacteria or any combination thereof. The above starch may be, for example, corn starch, tapioca starch, yam starch or sweet potato starch. The source of the polysaccharide may be, for example, a plant extract or a yeast or fungal fermentation. The above protein may be, for example, collagen or glycoprotein.

Preparation method of multi-unit active carrier chewing gum

The preparation method of the multi-unit active carrier chewing gum is as follows.

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

Next, the mixed product after the mixing is cut to an appropriate size and then processed into a desired shape to form the chewing gum body 102 in Fig. 1. Next, a spherical block is formed, for example, by a step of spheronization.

Finally, a mixture of hot sugar coating and the desired additive is applied to the surface of the chewing gum body 102 to form a chewing gum shell 104 to complete the manufacture 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 an African mango compound microparticle, and the active substance is an African mango extract. African mangoes are produced from the African mango (African mango, scientific name Irvingia gabonensis) in Cameroon, Africa. The extract of mango seeds helps regulate physiology, master key metabolic functions, and adjust the constitution from the base to achieve a healthy and beautiful effect (US 7537790).

In the test, the user was allowed to record the length of time in which the sweetness was present in the mouth by chewing (experimental group) or squashing (control group), and simultaneously recording the frequency of swallowing water.

The chewing gum is a unified candy-made round chewing gum, which has a long diameter of 1.5 cm, a short diameter of 1.2 cm, and a chewing gum shell thickness of 0.8 mm. Each chewing gum has an average weight of 2.4 grams and contains 200 mg of African mango compound granules (containing 50% by weight of African mango extract), sweeteners (including isomalt, sorbitol, maltitol syrup, and mellow alcohol). , aspartame, acesulfame lactone potassium, gum, perfume, soy lecithin, gum arabic, palm wax, antioxidant (dibutylhydroxytoluene), edible 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, an adult during a normal meal, 10 Minute appointments are swallowed 50 times. Adults swallow saliva 37 times an hour while sitting still. When adults speak, the frequency of swallowing will increase. In general, chewing increases the amount of saliva produced, and the higher the frequency of swallowing, the shorter the active substance can remain in the mouth, reducing the oral absorption rate of the active substance.

Comparing the control group (experimental examples 1-1 to 1-3) with the experimental group (experimental examples 1-4 to 1-6), it is known that since the experimental group has a chewing action, the amount of saliva secretion is large, which may be The higher the frequency of swallowing water is evidenced by the fact that the sweetness of the experimental group was present in the oral cavity for a shorter period of time than the control group. Moreover, the higher the frequency of swallowing water, the higher the frequency of the presence of sweetness in the oral cavity, the more the time of the oral administration.

Example 2: Hunger index before and after chewing gum consumption

In this embodiment, the multi-unit active carrier used is African Mango compound microparticles or bitter orange compound microparticle chewing gum, and the active substances thereof are African mango extract or bitter orange extract, respectively. The above-mentioned African mango extract, as described in the first embodiment, will not be described again. The bitter orange extract described above is extracted from the immature bitter orange (Citrus aurantium L.), especially the cyan peel. The extracted active substance contains synephrine, citric acid and hesperidine flavonoids. Biologists have found that bitter orange extract (especially furin is a norepinephrine) is a combination of inhibition Appetite and satiety, promote basal metabolic rate (the associated metabolic mechanisms include accelerating the consumption of energy by body tissues) and adjust physiological functions (including autonomic nervous system) to achieve weight loss and maintain healthy goals.

In the test, the user was allowed to record the length of time in which the sweetness was present in the mouth by chewing (experimental group) or squashing (control group), and simultaneously recording the frequency of swallowing water.

The chewing gum is a unified chewing gum preparation, which has a total length of 1.5 cm, a short diameter of 1.2 cm, and a chewing gum shell thickness of 0.8 mm. About 10 to 15% by weight of microparticles are added to each chewing gum, which are African mango compound particles or bitter orange compound particles. The African mango compound microparticles of each chewing gum were added in an amount of 100 mg, and the African mango compound microparticles contained 50% by weight of African mango extract and added mango flavors (Experiments 2-7 to 2-9). The bitter orange compound microparticles were added in an amount of 300 mg, and the bitter orange compound microparticles contained 6 wt% of bitter orange extract, and coffee flavor was added (Experimental Examples 2-10 to 2-12). In addition, sweeteners (including isomalt, sorbitol, maltitol syrup, menthol, aspartame, acesulfame potassium), gum, spices, soy lecithin, arabic Gum, palm wax, antioxidant (dibutylhydroxytoluene), edible yellow pigment No. 4, antioxidant (butylhydroxymethoxybenzene). The chewing gum shell is an orange icing shell.

In the following experimental examples, Experimental Examples 2-1 to 2-6 were a control group, and Experimental Examples 2-7 to 2-12 were experimental groups. The test method for the hunger index is the 10-component scale questionnaire. The index range from 1 to 10 is never hungry to very hungry. The subject's measurement index directly reflects the current state of hunger. The results obtained are listed in Table 2 below.

From the results of Table 2, it can be seen that the control group without the active substance (Experimental Examples 2-1 to 2-3) and the user's oral administration of the chewing gum (Experimental Examples 2-4 to 2-6) In the control group, the effect of reducing the hunger index was limited. On the contrary, when the user of the experimental group (Experimental Examples 2-7 to 2-12) used the chewing method to consume the chewing gum, the effect of reducing the hunger index was remarkable.

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

In this example, several different oral release activities were tested The dosage form of the substance compares the length of time the active substance is released in the oral cavity. The active substance used herein is vitamin C, so it is a test of the length of time that the sour taste stays in the oral cavity. Rinse the drinking water before testing to maintain sufficient and constant humidity and a constant temperature in the mouth. The dosage forms tested in the respective experimental examples are described below, and the results obtained are shown in Table 3.

In Experimental Example 3-2, the dosage form tested was a chewing gum containing a multi-unit active carrier of vitamin C. After peeling off the sugar-coated shell, the chewing gum was mixed with a multi-unit active carrier containing 200 mg of vitamin C microparticles (containing 115 mg of vitamin C), which was prepared by extrusion spheronization, extruded with a 1.0 mm stencil, rounded at 500 rpm, and served at 5 wt. % curcumin staining.

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

In Experimental Example 3-3, the dosage form tested was a sublingual absorption capsule containing vitamin C. The preparation method is that before filling, the head and the body of the No. 3 capsule (gelatin material, produced by Dafeng Company) are punctuated with three holes each of the 24th needle (outer diameter 0.67mm), and there are 6 holes. . Further, about 115 mg of lactose (purchased from Mingtai Co., Ltd.) and about 115 mg of vitamin C (purchased from Jude Company) were placed in the capsule. Each of the above materials can be directly used for making it because of its good fluidity and formability. Granules and directly ingots.

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

In Experimental Example 3-5, the dosage form tested was an ingot containing vitamin C. This lozenge contains 115 mg of lactose and 115 mg of vitamin C. The material is also a straight-through dosage form.

In Experimental Example 3-5, the dosage form tested was an orally disintegrating tablet containing vitamin C. The mouth-breaking tablet contains 100 mg of lactose, 100 mg of vitamin C and 30 mg of disintegrating agent (sodium starch glycolate), and the material is also a straight-through dosage form.

^a sublingual tactile sensation dissipating time

^b dissipating time with sublingual tactile sensation

^c about 2 seconds / time

From the results of Table 3, it was found that the sublingual absorption capsule (Experimental Example 3-3) allowed vitamin C to stay under the tongue for the longest time. The sublingual absorption capsule is designed to release vitamin C through the capsule cavity and to be contained in the sublingual compartment, so that the saliva containing the active ingredient is not easily swallowed into the gastrointestinal tract, so it has the highest sublingual absorption ratio. When vitamin C is directly mixed 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 acidity residence time in the mouth can be combined with the sublingual absorption capsule. (Experimental Example 3-3) was better than the mouth-breaking ingot (Experimental Example 3-6).

The sublingual ingot (Experimental Example 3-4), the mouth-containing ingot (Experimental Example 3-5) and the Oral Disintegration (Experimental Example 3-6) have a fast dissolving speed, but the vitamin C enters the stomach with the saliva swallowing reflex action. Therefore, most vitamin C is absorbed through the gastrointestinal tract rather than under the tongue.

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

In this embodiment, several different oral release actives are tested, comparing the rate of absorption of the active substance with the length of time during which the effective concentration in the blood is maintained. The active substance used here is a dimension He lives B2, so the color of urine can be known by the color of urine.

The preparation method of the multi-unit active carrier of vitamin B2 is as follows. Vitamin B2 and sucralose were first dissolved in a glyceride at 60-70 ° C. The weight ratio of vitamin B2, sucralose to glyceride was 0.50:0.05:0.45, and the total weight was 500 g. After homogeneous mixing, the mixture was allowed to cool rapidly to form a thin yellow mass. The obtained yellow thin piece was pulverized by a pulverizer and passed through a No. 40 sieve to obtain a yellow fine powder (containing vitamin B2 yellow fine powder mixed with glycine 50%). The obtained yellow thin piece was pulverized by a pulverizer, and sieved through a No. 40 sieve to obtain a yellow fine powder (the content of vitamin B2 was 50% by weight). Next, the yellow fine powder and the glycine acid were mixed, and the weight ratio of the yellow fine powder to the glycine was 3:7. Then, using a single-screw extruder (Chongqing Yingge, E50, orifice plate 0.6mm) and then adding 10wt% of distilled water to the total weight of the raw material, and then extruding it in a moisture-proof box for about 48 hours, forming a vitamin B-containing (15wt%). Active carrier (in the form of sponge granules). Next, lactose and 0.5% by weight of sucralose were added to prepare an active carrier containing vitamin B2 (10.8% by weight).

In Experimental Example 4-1, the dosage form used was a chewing gum containing vitamin B2 particles, but the outer shell was peeled off. The content of the vitamin B2 microparticles was 20% by weight, which contained 10.8% by weight of vitamin B2.

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

In Experimental Example 4-3, the dosage form used was sublingual absorption. Capsules. The preparation method is as follows: in the head and the body of the No. 3 capsule (gelatin material, produced by Dafeng Company), three holes are punched out by a 24 gauge needle (outer diameter 0.67 mm), and there are 6 holes. The capsule was then filled with about 230 mg of a vitamin B2 multi-unit active carrier containing 25 mg of vitamin B2.

In Experimental Example 4-4, the dosage form used was a mouth-containing ingot. Here, 230 mg of vitamin B2 microparticles (having 25 mg of vitamin B2) and 70 mg of lactose were tableted into an ingot containing 11 mm in diameter.

In Experimental Example 4-5, the dosage form used was an orally disintegrating ingot. Here, 230 mg of vitamin B2 microparticles (having 25 mg of vitamin B2), 30 mg of sodium starch glycolate (disintegrating agent), and 40 mg of lactose were tableted into an orally disintegrated ingot having a diameter of 10 mm.

The test method is to let the same person drink 300mL of drinking water at 9:00 in the next five days, and then take the vitamin B2 of various oral dosage forms of Experimental Examples 3-1 to 3-5. Next, the urine color was tested at different time points (09:00, 09:15, 09:30, 10:30, 13:00, and 15:00). The urine is compared by the color method, and the standard of the color method is shown in Table 4. The standard E is 09:00 urine when no vitamin B2 is taken, and the standard A~D is standard E and then added with different amounts of vitamin B2. The test results are shown in Table 5.

In general, if the active substance is absorbed by the oral cavity, the rate of entry into the blood circulation is faster because it is saved to the gastrointestinal tract for absorption. 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 Excess active substance is excreted through the kidneys. Relatively speaking, if the oral absorption rate is small, the active substance needs to wait until it reaches the gastrointestinal tract before it can be absorbed and enters the blood circulation, so it also reaches the kidney slowly.

As can be seen from Table 5, the fastest yellowing of urine is the sublingual ingot of Experimental Example 4-2, and the urine begins to turn yellow 15 minutes after consumption. Then, in the sublingual absorption capsule containing the vitamin B2 active microparticles of Experimental Example 4-3, the urine began to yellowish 15-30 minutes after the consumption. Finally, the mouth of the experimental example 4-4 and the mouth of the experimental example 4-5 were inoculated, and it took 90 minutes after the consumption, and the urine began to turn yellow.

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

When the color of urine changed from yellow to colorless, the time point of the ingot containing the experimental example 4-4 was the latest, and the chewing gum containing the vitamin B2 active microparticles of Experimental Example 4-1 was compared with Experimental Example 4-4. The time of the mouth containing the ingot is almost the same, which is 320 minutes after eating. Both show a certain rate of gastrointestinal absorption.

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, and can increase the release period of the active substance to increase the absorption of the active substance through the oral mucosa. Secondly, the active carrier can protect the active substance with various characteristics and make it in the process of making the chewing gum. No loss of activity during storage 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, and the present invention can be modified and modified without departing from the spirit and scope of the present invention. The scope is subject to the definition of the scope of the patent application attached.

100‧‧‧ chewing gum

102‧‧‧ chewing gum body

104‧‧‧ Chewing gum shell

106‧‧‧Active carrier

Claims (20)

A chewing gum comprising a plurality of active carriers, the chewing gum comprising: a chewing gum body, the material of which is mainly edible rubber; a chewing gum shell covering the chewing gum body; the chewing gum shell material is mainly a flavoring agent; and the plurality of active carriers are distributed in The chewing gum body, the chewing gum shell or a combination thereof; at least one active substance distributed in the active carrier, wherein the active substance is a biologically active solid or liquid substance, and the active carrier can withstand the temperature and pressure of the chewing gum manufacturing process It is sufficient to protect the active substance. The chewing gum of claim 1, wherein the active carriers comprise microparticles, microspheres, liposomes, sponge granules, dropping pills or any combination thereof. The chewing gum of claim 1, wherein at least a portion of the active carriers have a coating. The chewing gum of claim 3, further comprising a polymer in the coating of the active carrier, the polymer forming a mucus in the saliva to increase the time during which the active substance is retained 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 an alkyl alkyl methacrylate. , hydroxypropylcellulose, hydroxypropylmethylcellulose or any combination thereof. The chewing gum of claim 1 further comprising an absorption enhancer located in the chewing gum body, the chewing gum shell, the active carriers, or any combination thereof. The chewing gum according to claim 6, wherein the absorption enhancer comprises a surfactant, a fatty acid, an alcohol, an azone, a chitosan, a phospholipid liquid oily substance, a red-lighting agent, and a piperine or any combination thereof. The chewing gum of claim 7, wherein the fatty acid comprises a C ₈ -C ₂₀ saturated or unsaturated fatty acid. The chewing gum of claim 7, wherein the phospholipid liquid oily substance comprises lecithin. The chewing gum of claim 7, wherein the surfactant comprises an anionic surfactant or a cationic surfactant. The chewing gum of claim 7, wherein the red-lighting agent comprises ginger powder or an oil extract thereof, paprika and or oil extract, cinnamon powder, peppermint oil, wintergreen oil or cinnamon oil. The chewing gum of claim 1 further comprising an acid-base buffer in the chewing gum body, the chewing gum shell, the active carriers, or any combination thereof. The chewing gum of claim 12, wherein the acid-base buffer in the chewing gum body, the chewing gum shell or any combination thereof comprises a weak acid buffer comprising citric acid, malic acid, tartaric acid, phosphoric acid , lactic acid, gluconic acid, glucuronic acid, vitamin C, acetic acid or salicylic acid. The chewing gum of claim 12, wherein the acid-base buffer in the active carriers comprises a weak base buffer comprising bicarbonate. The chewing gum of claim 1 further comprising a viscous material in the active carrier. The chewing gum of claim 15, wherein the viscous substance comprises gelatin, starch, polysaccharide, hydroxypropyl methylcellulose, protein, polypeptide, dead bacteria or any combination thereof. The chewing gum of claim 1, wherein the active substance comprises a central appetite suppressant to suppress appetite of the user. The chewing gum of claim 17, wherein the central appetite suppressant comprises an African mango extract or a bitter orange extract. The chewing gum of claim 1, wherein the active substance comprises a metabolic improving agent. The chewing gum of claim 19, wherein the metabolism improving agent comprises a bitter orange extract.