KR20210033433A - Drug suspension for companion animals and method for manufacturing the same - Google Patents

Abstract

The present invention relates to a suspension composition for companion animals and a method for manufacturing the same. More specifically, the present invention relates to a suspension for companion animals with improved palatability and excellent storage stability, comprising water-soluble drug particles having a coating layer formed with two types of shell layers on a core drug. The suspension has improved flavor preferred by companion animals, especially cats, without additives such as sweeteners and flavoring agents, and thus has improved storage stability by maintaining the coating layer for a long time even after the introduction of the coating layer to mask the bitter taste, thereby being able to be widely used as the suspension for companion animals.

Description

Pharmaceutical suspension for companion animals and method for manufacturing the same {Drug suspension for companion animals and method for manufacturing the same}

The present invention relates to a suspension composition for companion animals and a method for preparing the same, and specifically, a suspension for companion animals including water-soluble drug particles having a coating layer having two types of shell layers formed on a core drug, and having improved palatability and excellent storage stability It is about. This has improved the flavor that pets, especially cats, can prefer without additives such as sweeteners and flavoring agents, and it has improved storage stability as the coating layer can be maintained for a long time even after introducing the coating layer to mask bitter taste. Available.

Recently, domestic and foreign companion animal breeding has been increasing rapidly as income level has increased, aging and single-person households become nuclear families. In the US, 53.5% of households with dogs or cats, 12.7% of households with dogs and cats in 2015, and 10.5% of households with other Pets, 76.7% of all households have companion animals. Is appearing.

In Korea, as the number of elderly households and single-person households increases, the number of households for breeding companion animals is increasing significantly. In 2015, it is surveyed that 21.8% of all households in Korea have companion animals. However, despite the rapid increase in companion animal households, medicines for companion animals in Korea are not largely industrialized and are dependent on imported products.

In particular, in the case of companion animals, it is difficult to take drugs to animals due to the bitter taste of the oral medicine. In particular, when taking the medicine to a cat, the cat owner is often surprised by bubbles in the mouth. It is very difficult to take medicine to small animals. As a method of taking medicine to a companion animal, there is a method of injecting liquid medicine by connecting a long tube to a syringe, and there is a method of forcibly administering a pill using a pillgun, but recently, the companion animal has not used a compulsory method. There is an increasing need for technology that can take this voluntarily.

Accordingly, it is a situation in which a suspension technology that can be administered by mixing a pharmacological component or other medicines is being developed since it contains the taste or aroma components that the companion animal likes.

On the other hand, in order to take such an oral medicine to a companion animal, it is convenient to take it in the form of a suspension. In foreign countries, most drugs applied to companion animals are sold as suspensions. However, in the case of such a suspension, storage stability and the like are deteriorated due to the formation of sediments, etc., and thus there is a hassle to prepare again within a short period of time. In addition, in the domestic veterinary drug market, multinational pharmaceutical companies are actively developing their business, accounting for most of the top-ranked sales product lines in the market, and the high percentage of imported products that requires localization of veterinary drugs.

Under this background, the inventors of the present invention attempted to develop a suspension with improved palatability and enhanced storage stability so that companion animals can eat spontaneously.

Korean Patent Application Publication No. 2008-0043742 (published on May 19, 2008) Japanese Patent Application Publication No. 2008-523024 (published on Jul. 03, 2008)

The present invention was devised in consideration of the above points, and the inventor of the present invention is that when a flavoring agent containing fatty acids is introduced on the surface of the coating layer of an aqueous drug on which a coating layer for masking taste is formed, the masking taste is shielded to improve palatability. It was confirmed that the coating layer for masking bitter taste can be maintained for a long time even after the introduction of the flavoring agent, and storage stability can be improved, thus completing the present invention.

Accordingly, an object of the present invention is to provide a suspension composition for companion animals having improved palatability and excellent storage stability.

In addition, an object of the present invention is to provide a suspension for companion animals having a storage stability of at least 60 days at a temperature of 40°C.

In addition, an object of the present invention is to provide a method for preparing the suspension for companion animals.

In order to achieve the above object, the present invention is a suspension composition comprising a water-soluble drug, a flavoring agent, and a thickener, wherein the water-soluble drug is a drug particle coated with an aqueous coating solution containing sodium arginate and chitin to form a coating layer. , A flavoring agent containing a fatty acid on the surface of the coating layer provides a suspension composition for companion animals.

In addition, the present invention provides a suspension for companion animals comprising the above suspension composition and having a storage stability of at least 60 days at a temperature of 40° C. and 75% absolute humidity.

In addition, the present invention comprises the steps of: (a) preparing a second mixture by dividing and stirring the flavor mixture into the first mixture in which a water-soluble drug and a water-soluble solvent are mixed; (b) preparing a third mixture by stirring while dividing an aqueous thickener solution into the second mixture; (c) adding and mixing an additive to the third mixture; And (d) finally preparing a suspension by adding an aqueous solvent or water to the mixture prepared in step (c).

The suspension composition according to the present invention has improved flavor that can be preferred by small animals without additives such as sweeteners and flavoring agents, and the coating layer can be maintained for a long time even after introduction of the coating layer for bitterness turn, so that it is not only a bitter taste masking but also storage stability. It is excellent in terms of physical properties as well.

In addition, the suspension composition according to the present invention does not use thickeners such as carrageenan and silicon dioxide, which can cause gastrointestinal problems or colorectal cancer, and minimizes the use of additives, such as not adding bitter surfactants. Because it is excellent in terms of safety, it is particularly suitable as a drug suspension for companion animals.

In addition, the suspension composition according to the present invention may enable localization of veterinary drugs.

1 is a cross-sectional view of a core/shell drug particle according to the present invention.

Conventionally, when the bitter taste of a drug is masked, the stability of the suspension may be broken, and when the suspension is stabilized, the masking of the bitter taste becomes incomplete, so studies on a suspension that can mask the bitter taste while maintaining the stability of the suspension are being continued. The present invention is a technology that solves all of these problems, and it is intended to improve storage stability by adding a technology capable of masking bitter taste of an oral drug.

In the present invention, a suspension means a liquid system having solid particles substantially dispersed throughout. Suspensions contain both liquid carriers containing substantially completely dissolved pharmaceutical actives or emulsions, which refer to liquids suspended in syrup formulations.

Hereinafter, the present invention will be described so that those skilled in the art can easily implement the present invention.

The present invention relates to a suspension composition for companion animals comprising drug particles to which a flavoring agent is bound to the surface of a coating layer for masking bitter taste. Specifically, the suspension composition according to an embodiment of the present invention includes a water-soluble drug, a flavor mixture, and an aqueous thickener solution on which a coating layer for masking bitter taste is formed.

In the present invention, the water-soluble drug is a water-soluble drug on which a coating layer for masking bitter taste is formed, and has the form of a core/shell drug particle to which a flavoring agent is further attached to the surface of the coating layer (see FIG. 1).

The water-soluble drugs are non-steroidal anti-inflammatory drugs (NSAIDs), ibuprofen, naproxen, flurbiprofen, fenoprofen, fenbufen, ketoprofen, indoprofen, pyrpropene, carprofen, oxaprozine , Pranoprofen, miroprofen, thioxaprofen, suprofen, aluminoprofen, thiapropenic acid, fluprofen, indomethacin, sulindac, tolmethine, jomepirac, nabumeton, diclofenac, Penclofenac, Alclofenac, Bromfenac, Ibufenac, Aceclofenac, Asemetacin, Penthiazac, Clidanac, Etodolac, Oxprinac, Mefenamic Acid, Meclofenamic Acid, Flufenamic Acid, Niflumic Acid, Any one selected from the group consisting of tolfenamic acid, diflunisal, flufenisal, piroxicam, tenoxicam, rornoxicam, meloxicam, nimesulide, amoxicillin and pharmaceutically acceptable salts thereof I can. Preferably, the water-soluble drug is meloxicam or amoxicillin.

Meloxicam inhibits the synthesis of prostaglandin, an inflammatory factor, by inhibiting the activity of cyclooxygenase (COX), and is used in the treatment of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis in companion animals. .

The amoxicillin is a penicillin antibacterial agent, and is an antibiotic that effectively acts on a wide range of gram-positive and negative bacteria.

As shown in Fig. 1, the water-soluble drug in the present invention is a drug particle coated with an aqueous coating solution to form a coating layer. Specifically, a coating layer is formed on the water-soluble drug by an aqueous coating solution, which can block the exposure of the bitter taste of the water-soluble drug in the mouth of the companion animal. When such an aqueous coating solution is mixed with a water-soluble drug, it may coat the surface of the drug to form a core/shell type drug particle.

The aqueous coating solution for masking these bitter tastes is sodium alginate, alginic acid, polymethyl methacrylate (Eudragit L30D, Eudragit LS30D, Kollicoat MP (manufactured by BASF), etc.), which are the main components of seaweed extracts such as seaweed, wheat protein, soy protein, methyl cellulose. (MC), hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose [HPMC; pharma coat, aqua coat, etc.], gums, such as guar gum, locust It may be one or more selected from the group consisting of Locust bean gum, Xanthan gum, Gellan gum, and Arabic gum.

Of these, sodium alginate is water-soluble or water-dispersible, so it has the advantage that it can be coated simply by using water as a solvent, and there is no need to use an organic solvent that is harmful to the human body to dissolve it. It is very meaningful in that there is no fundamentally. In other words, it is a distinct advantage that most polymer materials that have been used as coating bases in the past have to use an organic solvent to dissolve them. In addition, it has the advantage of protecting the gastrointestinal tract.

Accordingly, in the present invention, it is preferable to use an aqueous coating solution containing one of sodium arginate or chitosan or a mixture thereof. This is because the coating layer does not collapse even in the mouth, and the bitter taste can be masked by not exposing the drug in the oral cavity. Specifically, the aqueous coating solution may include 0.1 to 5% by weight of sodium arginate or chitosan, or a mixture thereof, and the balance of the water-soluble solvent based on the total weight of the aqueous coating solution. Preferably, it is 0.5 to 1% by weight of sodium arginate or chitosan, or a mixture thereof, and the water-soluble solvent may be glycerol, but is not limited thereto.

In addition, it is preferable that the drug particles have an average particle diameter of 10 to 50 μm. More preferably, it is 10 to 40 µm. If the average particle diameter is less than 10 µm, the smaller the particle, the faster the drug can be initiated in the gastrointestinal tract, but the surface area is too small to form a coating layer, so storage stability is not improved. It is firmly deposited on the bottom of the container and must be strongly shaken and redispersed when taking it, and when taking it, it is desirable to fall within the above range because unpleasant sensation occurs due to the gritty touch, which may lead to a decrease in palatability.

In the present invention, the flavoring agent may be attached to the surface of the aqueous gotting layer, and the flavoring agent includes a fatty acid. As shown in Fig. 1, fatty acids are attached to the surface of the coating layer of the water-soluble drug to form another shell layer. In the present invention, the fatty acid can prevent the collapse of the coating layer, thereby improving the storage stability of the drug particles in the suspension, and the fatty acid itself contributes to the improvement of palatability by affecting the flavor of small animals. function).

Specifically, the fatty acid is oleic acid, palmitic acid, azelaic acid, pimelic acid, capric acid, myristic acid, Palmitoleic acid, linoleic acid, linolenic acid, stearic acid, valeric acid, arachidonic acid, lauric acid, n -Butyric acid (n-butyric acid), isobutyric acid (isobutyric acid), [alpha]-methyl butyric acid ([alpha]-methylbutyric acid), pivalic acid (pivalic acid), y-linoleic acid (y-linoleic acid), eicosafen Carbonic acid (eicosapentanoic acid), pentadecanoic acid (pentadecanonic acid), tridecanoic acid (tridecanoic acid), docosahexanoic acid (docosahexanoic acid), derivatives thereof, and any one selected from the group consisting of ester or methyl ester derivatives have. Preferably, it contains at least one selected from the group consisting of oleic acid, palmitic acid, azelaic acid, and pimelic acid. Preferably, the fatty acid in the present invention may be at least one selected from the group consisting of oleic acid, palmitic acid, azelaic acid, and pimelic acid, and more preferably It is at least one selected from the group consisting of oleic acid and palmitic acid.

As an example, the fatty acid of the present invention is 10 to 30% by weight of oleic acid based on the total weight of the flavor mixture; And 1 to 10% by weight of palmitic acid. In the case of a flavor mixture, an emulsifier may be included in order to increase the solubility of the fatty acid.

Feline members of the feline family cannot express functional T1R2 monomers, and the taste receptors of the main functional T1R family in cats are known to be T1R1/T1R3 of taste receptors, and the fatty acids exhibit the activity of taste receptors such as T1R1/T1R3. Can be strengthened or adjusted.

In addition, the flavor mixture is composed of 2-methyl-2-butenal (2-Methyl-2-butenal), 2-ethyl-furan (2-Ethyl-Furan), and pentadecane (Pentadecane) together with fatty acids. At least one additive selected from the group may further include 0.01 to 2% by weight based on the total weight of the flavor mixture. It is preferably 0.1 to 1% by weight. 2-Methyl-2-butenal (2-Methyl-2-butenal) can be used within the above range because it helps to lower anxiety, stress and aggression of small animals such as dogs or cats. 2-Ethyl-Furan (2-Ethyl-Furan), and pentadecane (Pentadecane) are also materials that can improve palatability.

In the present invention, it is preferable to incorporate a thickener from the viewpoint of controlling the viscosity of the suspension and improving the sedimentation stability of the drug particles, as well as further improving the stability of the drug particles over time. This thickener may serve as an emulsifier, which may act as a linker so that the fatty acid of the flavoring agent can be attached to the surface of the coating layer.

The thickener aqueous solution may contain 0.5 to 5% by weight of microcrystalline cellulose, 0.01 to 0.5% by weight of carboxymethyl cellulose, and 0.1 to 1% by weight of Xanthan gum with respect to the total weight of the thickener aqueous solution. I can.

When microcrystalline cellulose, carboxymethyl cellulose, and xanthan gum are less than the above lower limit, the homogeneity of the formulation decreases over time, or in severe cases, there is a limit that precipitation (e.g., caking) occurs, and when it exceeds the upper limit, it becomes homogeneous due to high viscosity. It becomes very difficult to achieve a redistribution, and to overcome this, there is a limit that increases the complexity of the process due to the use of unnecessarily stronger mechanical force, for example, a homogenizer, etc., so that it is used within the above range. It is good.

On the other hand, or by the conventional suspension product ^ORAL-ⓡ PLUS product into the carrageenan (Carrageenan) component that causes the stomach or large intestine cancer, the present invention was to minimize these problems by not using the carrageenan. In addition, the use of additives was minimized, such as not using surfactants, silicon dioxide, etc., which realize bitter taste.

In addition, in the present invention, the pH of the suspension composition is preferably 2 to 5, and the suspension of pH 2 to 5 can be adjusted using a pH adjuster (for example, a citric acid buffer). The pH of the suspension is particularly preferably 2 to 4.

When the suspension composition of the present invention is 100% by weight of the suspension composition for companion animals, 3 to 10% by weight of a water-soluble drug; 15 to 35% by weight of aqueous coating solution; 0.1 to 5% by weight of the flavor mixture; 30 to 70% by weight of aqueous thickener solution; And a residual amount of water or a water-soluble solvent.

In addition, the aqueous solvent may further include a water-soluble solvent, which is a water-soluble polyhydric alcohol, in the suspension composition. For example, glycerol, but not necessarily limited thereto. The blending amount of the water-soluble polyhydric alcohol is 5 to 30% by weight, preferably 10 to 25% by weight. If it is less than 5% by weight, dispersibility and redispersibility of the suspension will be poor, and if it is more than 30% by weight, it has high viscosity and poor dosage.

The water-soluble drug is 3 to 10% by weight based on the total composition of the suspension, which may be used according to the type of drug.

The flavor mixture is 0.1 to 5% by weight, preferably 0.3 to 4% by weight. If the flavoring agent is less than 0.1% by weight, it is difficult to improve palatability, and if it is more than 5% by weight, there is a limit that may hinder palatability.

The aqueous thickener solution is 30 to 70% by weight, preferably 50 to 65% by weight. If the thickener is less than 30% by weight, the homogeneity of the aqueous drug suspension decreases over time, or in severe cases, there is a limit that precipitation (e.g. caking) occurs, and if it exceeds 70% by weight, it becomes a high viscosity, resulting in homogeneous redistribution. It becomes very difficult to achieve this, and there is a limitation in that the complexity of the process is added as the use of unnecessarily stronger mechanical force, for example, a homogenizer, etc. is used to overcome this.

In the suspension composition of the present invention, other medicinal ingredients such as sodium copper chlorophyllline, azulene, allantoin, aluminum allantoinate, silicone oil, scofolia extract, cinnamon oil, clove oil, other herbal ingredients, atropine, scopolamine, Gastrointestinal medicines such as ethyl aminobenzoate, vitamins B1, B2, B6, vitamin C, vitamin A, vitamin D, vitamin E, calcium aspartate, calcium lactate, antipyretic analgesics, muscle relaxants, ginseng Convulsants, antihistamines, sympathetic stimulants, and the like can be blended within a range that does not impair the effects of the present invention.

In addition, substances commonly used in pharmaceutical technology, such as pharmaceutically acceptable sweeteners, pH adjusters, preservatives, flavoring agents, colorants, antifoaming agents, and antioxidants, may be blended.

Examples of the sweetener include lactose, sucrose, fructose, glucose, sorbitol, mannitol, erythritol, xylitol, trehalose, and stevia extract, but are not limited thereto. In this case, the sweetener may be used in an amount of 0.1 to 3% by weight based on the total weight of the suspension composition.

Examples of the pH adjuster include lactic acid, citric acid, malic acid, succinic acid, fumaric acid, tartaric acid, phosphoric acid, and salts thereof. In this case, the pH adjusting agent may be used in an amount of 1 to 3% by weight based on the total weight of the suspension composition.

Examples of the preservative include parabens such as methyl p-oxybenzoate, ethyl p-oxybenzoate, propyl p-oxybenzoate, and butyl p-oxybenzoate, and benzoic acid or salts thereof. At this time, the preservative may be used in an amount of 0.1 to 1% by weight based on the total weight of the suspension composition.

As for flavoring, orange, grapefruit, apple, lemon, lime, tangerine, citron, wenju mandarin, summer tangerine, grape, strawberry, pineapple, banana, peach, melon, watermelon, cucumber, celery, pear, apple coat, karant , Plum, mango, mangosteen, cuava, roseberry, blueberry and other fruit aromas, green tea, black tea, cocoa, chocolate, coffee, amondo, maple, vanilla, whiskey, brandy, rum, wine, liqueur, cocktail , Mint, and the like, and these may be used alone or as a mixed scent. At this time, the fragrance may be used in an amount of 0.1 to 1% by weight based on the total weight of the suspension composition.

As the antifoaming agent, Simethicone, Wacker, Rhodia, a silicone material from Dow Corning, an acetylene material, such as an acetylene material from Air Products, etc. can be used. In this case, the antifoaming agent may be used in an amount of 0.01 to 1% by weight based on the total weight of the suspension composition.

Examples of antioxidants include tocopherol, derivatives of tocopherol, derivatives of tocopherol, alpha tocopherol, tocopheryl acetate, tocopheryl succinate, ascorbic acid, derivatives of ascorbic acid, tetrahexyldecyl ascorbate, butylated hydroxyl toluene (BHT), Butylated hydroxyanisole and the like can be used. In this case, the antioxidant may be used in an amount of 0.01 to 1% by weight based on the total weight of the suspension composition.

As such, the suspension containing the suspension composition according to the present invention has storage stability for at least 60 days at a temperature of 40° C., and palatability is improved by masking bitterness and improving flavor, so that it can be provided as a suspension for companion animals.

In addition, the present invention provides a method for preparing a suspension that can conveniently and easily prepare a suspension having excellent properties as described above. In order to implement the drug particles in which the flavoring agent is bound to the surface of the coating layer for masking bitter taste according to the present invention, a mixing method of an aqueous coating solution, a thickener, and a flavoring agent is important.

Specifically, a method for preparing a suspension according to another embodiment of the present invention includes the steps of: (a) preparing a second mixture by dividing and stirring the flavor mixture into a first mixture in which a water-soluble drug and a water-soluble solvent are mixed; (b) preparing a third mixture by stirring while dividing an aqueous thickener solution into the second mixture; (c) adding and mixing an additive to the third mixture; And (d) adding an aqueous solvent or water to the mixture prepared in step (c) to finally prepare a suspension. Splitting, administering multiple times, and mixing helps to ensure even distribution of the drug and the stability of the suspension.

At this time, in the present invention, 3 to 10% by weight of the water-soluble drug, 0.1 to 5% by weight of the flavor mixture, and 30 to 70% by weight of the thickener aqueous solution may be used based on the total weight of the suspension composition. The water-soluble solvent may be used when preparing the first mixture and also when preparing an aqueous coating solution for ease of mixing. A detailed description of the composition used in each step is duplicated with the above description, so the description thereof will be omitted.

Specifically, step (a) is a step of preparing a second mixture by dividing the first mixture in which a water-soluble drug is mixed in a water-soluble solvent and a flavor mixture to be added while stirring.

Next, the step (b) is a step of preparing a third mixture by dividing and stirring the aqueous thickener solution to the second mixture, and mixing while adding a third mixture little by little to the second mixture to improve dispersibility. desirable.

Specifically, it can be seen as the most important step in the method of preparing a suspension because it is very advantageous in improving dispersibility and forming a coating layer by mixing by stirring while dividing into 5 to 15 times.

At this time, the water-soluble drug is in the form of finely pulverized particles, and the average particle diameter of the drug particles in the suspension is 10 to 50 µm or less, particularly preferably 10 to 40 µm. If the average particle diameter is less than 10 µm, the smaller the particle, the faster the drug can be initiated in the gastrointestinal tract, but the surface area is too small to form a coating layer, so storage stability is not improved. It is firmly deposited on the bottom of the container and must be strongly shaken and redispersed when taking it, and when taking it, it is desirable to fall within the above range because unpleasant sensation occurs due to the gritty touch, which may lead to a decrease in palatability.

The step (c) is a step of mixing an additive in the third mixture, and the additive may be a pH adjuster, an antifoaming agent, an antioxidant, and a preservative, but is not limited thereto.

Finally, in step (d), the remaining amount of water-soluble solvent or water may be added to the mixture prepared in step (c) to prepare a suspension, which is a homogeneous mixture.

The suspension composition according to the present invention thus prepared has improved flavor that can be favored by small animals, especially felines, without additives such as sweeteners and flavoring agents, and can maintain a coating layer for masking bitter taste for a long time, so that it is possible to shield the bitter taste as well as store it. As the stability is also improved, it can be widely used as a drug suspension for companion animals.

Hereinafter, examples will be described in detail to aid understanding of the present invention. However, the following examples are merely illustrative of the contents of the present invention, and the scope of the present invention is not limited to the following examples. The embodiments of the present invention are provided to more completely describe the present invention to those of ordinary skill in the art.

Example 1

The composition of the suspension of the present invention is shown in Table 1, and a suspension was prepared using the composition of Table 1 below. Specifically, a first mixture was prepared by mixing a water-soluble drug with a water-soluble solvent, and a second mixture was prepared by adding a flavor mixture thereto. At this time, the second mixture was gradually stirred and mixed while being divided into the first mixture 10 times. Next, a third mixture was prepared by dividing and stirring an aqueous thickener solution into the mixture 10 times. Next, a pH adjuster, an antifoam, an antioxidant, and a preservative were added as additives, mixed, and finally water was added to prepare 300 ml of a suspension.

division ingredient Example 1 (A)
First mixture Water soluble drugs Amoxicillin 12 ml (10 g)
Water-based coating solution ¹⁾
Alginate/Glycerol ¹⁾ 78ml Sum 90ml (B)
Second mixture Flavor Mixture ²⁾ Oleic acid 1.6ml Palmitic acid 0.5ml Polysorbate 20 (emulsifier) 6ml water q.s. Sum 10ml (C)
Third mixture Aqueous thickener solution Microcrystalline Cellulose (MCC) 2.4g Carboxymethyl Cellulose (CMC) 0.3g Xanthan 0.3g water q.s. Sum 190ml (D)
additive Ph modulator Citric Acid 5.4ml Antifoam Simethicone 0.03g Antioxidant Butylated HydroxyToluene (BHT) 0.03g Preservative (preservative) Sodium Benzoate 0.3g (E) water q.s. Total sum 300ml 1) The aqueous solvent glycerol (Glycerol) solution contains 0.5% by weight of alginate (or chitosan) based on the total weight of the aqueous coating solution.

Comparative Example 1: General suspension containing only uncoated drug particles

A suspension was prepared using the same composition as in Table 1, but the aqueous coating solution and flavoring agent were not used. At this time, 300 ml of a suspension was prepared by adding water as much as the unused amount of the aqueous coating solution and flavoring agent.

Comparative Example 2: Suspension containing uncoated drug particles and flavoring agent

A suspension was prepared using the same composition as in Table 1, but an aqueous coating solution was not used. At this time, 300 ml of a suspension was prepared by adding water as much as the unused amount of the aqueous coating solution.

Comparative Example 3: Suspension containing only water-based coated drug particles

A suspension was prepared using the same composition as in Table 1, but no flavoring agent was used. At this time, 300 ml of a suspension was prepared by adding water as much as the unused amount of the flavoring agent.

Experimental Example 1: Storage stability confirmation experiment

The suspensions of Example 1 and Comparative Examples 1 to 2 were put in a brown polyethylene (PE) prescription container and subjected to a harsh test method (40° C. and 75% absolute humidity), which is a method notified by the Ministry of Food and Drug Safety, with a humidity of 75% for 120 days, It was stored at 25°C and 40°C, and the change in the active ingredient content of the drug was measured by HPLC (High Performance Liquid Chromatography).

In addition, the color change was observed with the naked eye and scored (0: white (no change), 1: pale yellow, 2: medium yellow, 3: dark yellow). Odors were also scored and evaluated (0: none (odorless), 1: light chemical odor, 2: medium chemical odor, 3: strong chemical odor, 4: very severe chemical odor). Whether sedimentation or layer separation was generated was evaluated by visual observation (0: none, 1: light layer separation, 2: distinct layer separation)

Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Time
(Days) 25℃ 40℃ 25℃ 40℃ 25℃ 40℃ 25℃ 40℃ 0 100 ¹⁾ 100 ¹⁾ 100 ²⁾ 100 ²⁾ 100 ³⁾ 100 ³⁾ 100 ⁴⁾ 100 ⁴⁾ 7 99.3 99.1 98.3 97.9 97.1 98.3 101.2 99.2 14 99.1 100.2 92.9 93.1 93.8 94.2 98.9 99.1 30 97.6 98.6 84.6 83.1 87.3 89.1 98.3 98.4 60 98.7 96.4 77.8 76.7 80.7 81.3 98.6) 97.6 120 96.9 95.1 72.2 72.3 79.3 77.1 95.9 96.8 color 0 0 2 2 One One 0 0 smell 0 0 2 3 0 0 0 0 Whether sedimentation or delamination is generated 0 0 2 2 One One 0 0 1) At the time of initial measurement, the active ingredient is 24.92mg/ml, which is expressed as 100% and the amount of change over time is measured.
2) At the time of initial measurement, the active ingredient was 25.72mg/ml, which was 100% and the amount of change over time was measured and indicated.
3) At the time of initial measurement, the active ingredient is 24.88mg/ml, which is expressed as 100% and the amount of change over time is measured.
4) At the time of initial measurement, the active ingredient is 26.12mg/ml, which is expressed as 100% and the amount of change over time is measured.

As a result, in the case of Example 1 prepared according to the present invention, it was confirmed that the stability of the suspension was maintained under severe conditions. However, in the case of a suspension containing uncoated drug particles that are not water-based, the active ingredient concentration of the drug decreases, and the color changes from white to yellow, from odor to chemical odor, and sediment formation. There was a problem.

Therefore, it was confirmed that the stability of the drug can be improved when the water-soluble drug particles according to the present invention are coated with an aqueous coating solution.

Experimental Example 2: Preference Confirmation Experiment

<Experimental Example 2-1> Confirmation of palatability

In order to evaluate the palatability, the consumption preference of cats was investigated. Specifically, 28 cats were randomly grouped into 112 cats that did not show any health abnormalities in a physical examination, general blood test, and radiographic examination by a veterinarian. After ingesting a wet feed mixed with a drug mixed with amoxicillin powder, palatability was evaluated by checking the palatability and stress-related response after ingestion.

1) Reaction time: The time it took for a cat to lick it for ingestion was measured after showing interest in the drug at the administration device.

2) Ear posture confirmation: Based on a previously known method (Applied Animal Behavior Science 173 (2015) 68-75), the shape and posture of the cat's ears were observed and evaluated (1: relaxed/warning ears (straight) , Facing forward), 2: Erect ears but facing sideways, 3: Ears facing down, 4: Ears are flat on the head, 5: Ears are moderately flat and the top of the ear rotates forward).

3) Confirmation of pupil dilation: The cat's pupil was observed and evaluated (1: relaxed eye (no pupil dilation), 2: slightly dilated pupil, 3: slightly dilated pupil, 4: Very dilated pupil, 5: narrow slit pupil).

Classification (Sample) Reaction time Ear posture Pupil dilation One Drugs (tablets) - 2.6±(0.8)
(2.0-4.0) 2.7±(0.9)
(2.0-4.0) 2 Drug + water - 2.1±(0.5)
(1.0-3.0) 2.4±(0.4)
(2.0-4.0) 3 Example 1 Average 2.9 seconds 1.7±(0.6)
(1.0-3.0) 1.6±(0.4)
(2.0-4.0) 4 Drug + Wet Feed 2.3 seconds on average 1.2±(0.3)
(1.0-2.0) 1.1±(0.3)
(2.0-4.0) * Mean(S.D.) and range of physiologic parameter from 112 cats

division Stress-related reaction ³⁾ (Unit: number of animals) Drooling throw up Eye disease ¹⁾ Respiratory abnormalities ²⁾ Blood sugar level ³⁾
(Blood Glucose) mg/dl One Drugs (tablets) 5 3 3 2 104.8±(17.8)
(86.3-147.4) 2 Drug + water 3 3 4 3 106.3±(13.7)
(88.2-130.6) 3 Example 1 One 0 0 0 93.4±(11.8)
(82.0-112.0) 4 water 0 0 0 0 95.8±(13,8)
(82.1-121.4) * Mean(SD) and range of physiologic parameter from 112 cats
1) Eye diseases include all diseases that occur in the eye, including the eyelid and conjunctivitis.
2) Respiratory abnormalities include all respiratory diseases including cough and runny nose.
3) In case of stress, there are symptoms of drooling, vomiting, eye disease, respiratory abnormalities, and even the blood sugar level rises compared to normal.

From the results of Tables 3 and 4, it was confirmed that in the case of the suspension formulation according to the present invention, preference for ingestion can be improved compared to other formulations.

<Experimental Example 2-2>

It was confirmed in the same manner as in Experimental Example 2-1, but palatability was evaluated for Example 1 and Comparative Examples 1 to 3.

division Reaction time Ear posture Pupil dilation One Example 1 Average 2.9 seconds 1.7±(0.6)
(1.0-3.0) 1.6±(0.4)
(2.0-4.0) 2 Comparative Example 1 - 3.6±(0.6)
(2.0-4.0) 3.4±(0.4)
(2.0-4.0) 3 Comparative Example 2 Average 4.7 seconds 2.4±(0.6)
(1.0-3.0) 2.4±(0.5)
(1.0-3.0) 4 Comparative Example 3 3.9 seconds on average 1.8±(0.5)
(1.0-3.0) 1.7±(0.4)
(1.0-3.0) * Mean(S.D.) and range of physiologic parameter from 112 cats

division Stress-related reaction ³⁾ (Unit: number of animals) Drooling throw up Eye disease ¹⁾ Respiratory abnormalities ²⁾ Blood Glucose mg/dl One Example 1 2 One One 0 94.4±(9.8)
(79.0-112.0) 2 Comparative Example 1 11 4 4 3 105.8±(17.8)
(86.3-132.6) 3 Comparative Example 2 8 3 3 2 102.3±(13.7)
(85.2-130.6) 4 Comparative Example 3 4 One 2 2 96.1±(8.8)
(82.1-117.4) * Mean(SD) and range of physiologic parameter from 112 cats
1) Eye diseases include all diseases that occur in the eye, including the eyelid and conjunctivitis.
2) Respiratory abnormalities include all respiratory diseases including cough and runny nose.
3) In case of stress, there are symptoms of drooling, vomiting, eye disease, respiratory abnormalities, and even the blood sugar level rises compared to normal.

As a result of Tables 5 and 6, in the case of Example 1 prepared according to the present invention, it was confirmed that the cat had the least rejection. When a flavoring agent was used in the suspension, it was again confirmed that the cat's preference was high.

As the specific parts of the present invention have been described in detail above, it will be apparent to those of ordinary skill in the art that these specific techniques are only preferred embodiments, and the scope of the present invention is not limited thereby. will be. Accordingly, it will be said that the substantial scope of the present invention is defined by the appended claims and their equivalents.

Claims (10)

In a suspension composition comprising a water-soluble drug, a flavor mixture, and an aqueous thickener solution,
The water-soluble drug is a drug particle coated with an aqueous coating solution containing one of sodium arginate or chitosan or a mixture thereof to form a coating layer,
A suspension composition for companion animals, characterized in that a flavoring agent containing a fatty acid is attached to the surface of the coating layer.
The method of claim 1,
The aqueous coating solution is characterized in that it comprises 0.1 to 5% by weight of one of sodium arginate or chitosan or a mixture thereof based on the total weight of the aqueous coating solution, suspension composition for companion animals.
The method of claim 1,
The fatty acid is oleic acid, palmitic acid, azelaic acid, pimelic acid, capric acid, myristic acid. , Palmitoleic acid, linoleic acid, linolenic acid, stearic acid, valeric acid, arachidonic acid, lauric acid, n-butyric acid, isobutyric acid, [alpha]-methylbutyric acid, pivalic acid, y-linoleic acid, Eiko Sapentanoic acid (eicosapentanoic acid), pentadecanoic acid (pentadecanonic acid), tridecanoic acid (tridecanoic acid), docosahexanoic acid (docosahexanoic acid), derivatives thereof, and any one selected from the group consisting of ester or methyl ester derivatives Characterized in that, a suspension composition for companion animals.
The method of claim 1,
The flavor mixture is based on the total weight of the flavor mixture
10 to 30% by weight of oleic acid; And
1 to 10% by weight of palmitic acid;
Characterized in that it comprises a, suspension composition for companion animals.
The method of claim 4,
The flavor mixture was used as 2-Methyl-2-butenal, 2-Ethyl-Furan, and Pentadecane based on the total weight of the flavor mixture. A suspension composition for companion animals, characterized in that it further comprises 0.01 to 2% by weight of one or more additives selected from the group consisting of.
The method of claim 1,
The drug particles are characterized in that the average particle diameter of 10 to 50 ㎛, suspension composition for companion animals.
The method of claim 1,
The thickener aqueous solution comprises 0.5 to 5% by weight of microcrystalline cellulose, 0.01 to 0.5% by weight of carboxymethyl cellulose, and 0.1 to 1% by weight of Xanthan gum with respect to the total weight of the thickener aqueous solution. Characterized in that, a suspension composition for companion animals.
The method of claim 1,
The composition is based on the total weight of the suspension composition,
3 to 10% by weight of a water-soluble drug;
15 to 35% by weight of aqueous coating solution;
0.1 to 5% by weight of the flavor mixture;
30 to 70% by weight of aqueous thickener solution; And
Residual amount of water or water-soluble solvent;
Characterized in that it comprises a, suspension composition for companion animals.
The method of claim 1,
The suspension composition is characterized in that the pH is 2 to 5, suspension composition for companion animals.
(a) preparing a second mixture by dividing the flavor mixture into the first mixture in which a water-soluble drug and a water-soluble solvent are mixed, while stirring;
(b) preparing a third mixture by stirring while dividing an aqueous thickener solution into the second mixture;
(c) adding and mixing an additive to the third mixture; And
(d) finally preparing a suspension by adding an aqueous solvent or water to the mixture prepared in step (c).

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