Animal edible medicine-containing ball-shaped composition as well as preparation method and application thereof

Abstract

The invention discloses an edible medicine-containing ball-shaped composition for animals as well as a preparation method and application of the edible medicine-containing ball-shaped composition. A briquetting machine, a coating machine and a tablet press which are sold in the market are combined and applied to the pharmaceutical field and the animal health care product field; medicine or bioactive substances are firstly prepared into medicine balls, then the prepared medicine balls are embedded and pressed into blocks with embedding materials which animals like to eat, and therefore the oral blocky composition which can be accepted by the animals is prepared, and the problem that the animals (cats, dogs, pigs, cows, sheep, horses, deer, camels and the like) are difficult to feed medicine is solved.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of animal health, in particular to a kind of animal edible medicine-containing ball-shaped composition and its preparation method and application. BACKGROUND

[0002] Most drugs and biologically active substances often have such or that the smell of animals do not like, and poor palatability, cats, dogs and other animals will not take food voluntarily; This brings certain resistance to the popularization and application of oral dosage forms prepared from drugs or poorly palatable active substances in the field of animal health.

[0003] In order to solve the problem that animals, especially pet cats and dogs, refuse to eat most drugs, and do not like to eat many functional health products (such as Chinese herbal medicine extracts, etc.), people have carried out extensive research, but most of them have not achieved the expected effect. For example, our previous test results show that: (1) In the preparation of tablets, granules and other solid preparations, directly mix the taste masking agent and the active ingredient or drug with heavy odor (such as pyrantel with very heavy odor and bitter taste, and extremely bitter berberine) together and add evenly, even if the addition ratio of the two reaches 150:1, the voluntary feeding rate of pet dogs is less than 19%, and the voluntary feeding rate of pet cats is less than 12%; (2) The drug with bitter taste (such as pyrantel) is prepared into microcapsules by coating technology, and then the microcapsules and the taste masking / feeding inducing components are evenly mixed together to prepare tablets or granules. Even in the case of empty stomach, the voluntary swallowing rate of pet dogs is less than 32%, the voluntary feeding rate of pet cats is less than 21%, and the voluntary feeding and swallowing rate of rural guard dogs in the case of semi-starvation can only reach about 41%.

[0004] Patent CN107412185A discloses a soft capsule containing feeding inducing components for dogs and cats; patent CN111214657A proposes a soft capsule containing feeding inducing agents for dogs and cats; patent CN201610423983.9 proposes a drop pill preparation containing feeding inducing agents for dogs and cats; and patent CN107496368A proposes a pill containing anti-parasitic drugs and feeding inducing agents for dogs and cats. The core technical content disclosed in the above patent applications is basically the same, i.e. the structure of the drug-containing solid preparation (composition) can be divided into two layers, the inner layer and the outer layer, the inner layer contains drugs, and the outer layer contains taste masking and feeding inducing components; the inner layer is encapsulated by the outer layer, hoping to achieve that dogs and cats can eat without coercion. However, due to the feeding characteristics of dogs and cats, the above-mentioned preparations are easily bitten and broken when dogs and cats eat, which exposes the internal drugs and further affects the feeding of the drugs. SUMMARY

[0005] The present application proposes to prepare the medicine or active substance which is not willing to eat by animals into medicine ball, then coat or uncoat the medicine ball, and then embed the medicine ball with embedding material to prepare the animal acceptable oral block composition.

[0006] In order to achieve the above-mentioned purpose, the present application adopts the following technical scheme:

[0007] A preparation method of the animal edible medicine ball block composition, the medicine or biological active substance is prepared into medicine ball, then the medicine ball is coated or uncoated, and then the medicine ball is embedded with embedding material to prepare the medicine ball block composition.

[0008] Preferably, the medicine or biological active substance is mixed with excipient, and a tablet machine, a pill machine, a drop pill machine or a screw extruder is used to prepare the medicine ball.

[0009] Preferably, the block is prepared by using a block machine, and the operating pressure is 500-700 MPa.

[0010] Preferably, a medicine ball quantitative transfer device is used to fill the medicine ball into the block machine, and the medicine ball quantitative transfer device is sequentially provided with a ball pressing plate, a ball containing plate, a hole sealing plate and a positioning plate from top to bottom.

[0011] The ball containing plate is provided with a through ball containing hole corresponding to the membrane hole of the block machine, the ball containing plate is provided with a plug plate slot on the side facing the hole sealing plate, and the other side is provided with a medicine adding slot.

[0012] The ball pressing plate is provided with a cylinder corresponding to the ball containing hole on the side facing the ball containing plate, and the top of the cylinder is an inwardly recessed arc.

[0013] The hole sealing plate is a flat plate, and the hole sealing plate is inserted into the plug plate slot.

[0014] The positioning plate is provided with a positioning column corresponding to the membrane hole of the block machine on the side away from the hole sealing plate, and the positioning column is provided with a through positioning hole corresponding to the ball containing hole; and the cylinder can penetrate into the ball containing hole and the positioning hole.

[0015] Preferably, a medicine ball quantitative transfer device is used to fill the medicine ball into the block machine, and the medicine ball quantitative transfer device is sequentially provided with a ball containing plate and a hole sealing plate from top to bottom.

[0016] The ball containing plate is provided with a through ball containing hole corresponding to the membrane hole of the block machine, the ball containing plate is provided with a plug plate slot on the side facing the hole sealing plate, and the other side is provided with a medicine adding slot.

[0017] The hole sealing plate is a flat plate, and the hole sealing plate is inserted into the plug plate slot.

[0018] Preferably, the diameter of the medicine ball is 3-10 mm, preferably 3-8 mm, and the diameter of the medicine ball containing hole is 1-4 mm larger than the diameter of the medicine ball.

[0019] Preferably, the preparation method of the medicine ball-containing edible block composition for animals comprises the following steps:

[0020] S1, medicine ball preparation: mixing the medicine or bioactive substance with excipients, granulating or not, using a tablet press, pill making machine, drop pill machine or screw extruder to prepare the medicine ball, which is spherical or near spherical;

[0021] S2, filling the medicine ball into the quantitative dispenser: when each block composition contains one medicine ball, insert the hole sealing plate of the quantitative transfer device into the insertion plate slot to seal all the medicine ball containing holes, then pour the medicine ball into the medicine adding slot, and use the scraper to sweep the medicine ball into the medicine ball containing hole;

[0022] When each block composition contains multiple medicine balls, use the quantitative dispenser to perform multiple dispensing, place the medicine ball-loaded quantitative dispenser on the ball containing plate of the medicine ball quantitative transfer device, make the ball containing holes on the quantitative dispenser correspond one-to-one with the medicine ball containing holes on the medicine ball quantitative transfer device, then pull out the hole sealing plate of the quantitative dispenser from the insertion plate slot to make the medicine balls in the ball containing holes fall one-to-one into the medicine ball containing holes, and set the dispensing times according to the number of medicine balls contained in each block composition;

[0023] S3, preparation of embedding material embedding the medicine ball: uniformly mix the animal food, food attracting flavor enhancer, adhesive, preservative, add wetting agent, fully stir and soak, and mix uniformly to obtain the embedding material;

[0024] S4, filling the bottom layer embedding material into the die hole of the briquetting machine;

[0025] S5, transferring the medicine ball: place the medicine ball quantitative transfer device loaded with the medicine ball on the die of the briquetting machine, make the positioning column fall one-to-one into the die hole of the briquetting machine, pull out the hole sealing plate to make the medicine ball fall into the die hole of the briquetting machine, then use the cylinder of the ball pressing plate to press the medicine ball in each die hole through the medicine ball containing hole and the positioning hole, press part of the medicine ball into the bottom layer embedding material, and then remove the medicine ball quantitative transfer device;

[0026] S6, filling the upper layer embedding material and pressing;

[0027] S7, drying, coating or not coating the food attracting agent to obtain the block composition.

[0028] Preferably, the bottom layer embedding material accounts for 15%-75% of the total embedding material.

[0029] The beneficial effects of the present application are as follows:

[0030] 1. The present application combines the commercially available briquetting machine, coating machine and tablet press in the field of pharmaceutical and animal health products; it is to prepare the medicine or bioactive material into medicine ball, and then embed the prepared medicine ball with the embedding material which is liked by animals, so as to prepare the animal acceptable oral block composition, which solves the problem of animal feeding difficulty. The hardness of the block composition prepared by the present application is large, and it is not easy to be bitten when the dog and cat eat, so as to ensure that the internal medicine will not release its odor, and realize the effect of animal active eating, so as to solve the problem of animal (cat, dog, pig, cow, sheep, horse, deer, camel, etc.) feeding "medicine".

[0031] 2. In order to improve the preparation efficiency and drug content of the block composition, the medicine ball quantitative dispenser and quantitative transfer device are designed, which can realize continuous and efficient production.

[0032] The actual operation shows that the medicine ball filling process of more than 50 medicine ball quantitative transfer devices can be completed in about 8 minutes, that is, at least 6600 medicine balls can be filled into 6600 medicine ball containing holes (for example, 132 holes / set quantitative transfer device x 50 sets) in about 8 minutes; it can be seen that the process of filling medicine balls into the medicine ball containing hole will not become a limiting factor of production efficiency, which reflects the advancement and practicality of the technology of the present application.

[0033] Under normal circumstances, the medicine balls in the medicine ball quantitative transfer device are transferred one by one into the die hole of the briquetting machine, and the operation time is 5-10 seconds, therefore, the medicine ball transferring process will not become a limiting factor of production efficiency; and due to the application of the medicine ball quantitative transfer device, the same number (one or more than one) of medicine balls with the same drug content can be added into each die hole of the briquetting machine, which overcomes the defect that the weight difference between the block materials pressed by the commercially available briquetting machine at present is large (more than 10%), which cannot meet the application in the field of pharmaceutical. BRIEF DESCRIPTION OF DRAWINGS

[0034] Figure 1 : The photo of the medicine ball quantitative transfer device provided by the present application;

[0035] Figure 2 : The photo of the medicine ball quantitative transfer device provided by the present application;

[0036] Figure 3 : The photo of the assembled ball containing plate and hole sealing plate provided by the present application;

[0037] Figure 4 : The photo of the positioning plate provided by the present application. DETAILED DESCRIPTION

[0038] The technical solutions in the embodiments of the present application will be clearly and completely described below. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative work fall within the protection scope of the present application.

[0039] The present application proposes that an animal-unwilling-to-eat drug or active substance is first prepared into a drug ball, and then the drug ball is coated (or not coated), and then the drug ball is embedded (i.e. pressed into a block) with an animal-willing-to-eat embedding material to prepare an animal-acceptable oral block-shaped composition. The main equipment used for preparing the block-shaped composition includes a commercially available tablet press or a similar device (such as a dripping pill machine, a traditional Chinese medicine pill making machine), a coating machine (or a coating pot), a briquetting machine and a drug ball quantitative transfer device specially manufactured according to the size of the briquetting machine mold and the diameter of the drug ball.

[0040] The basic technical requirement for applying a commercially available briquetting machine to the field of animal pharmacy and the field of animal health products is to achieve the same standard of drug content or active ingredient content in each block-shaped composition, and to achieve the expected encapsulation effect and feeding effect by embedding the drug ball with the embedding material. The following five aspects are important factors to achieve the above technical objectives.

[0041] (1) Determine the block size of the block-shaped composition according to the diet of different animals, and determine the size of the drug ball according to the size of the block-shaped composition block;

[0042] (2) Select the mold of the briquetting machine according to the shape and size of the determined block-shaped composition;

[0043] (3) The self-made drug ball quantitative transfer device has a number of drug ball containing holes and hole distribution, which need to be determined according to the structure of the briquetting machine mold;

[0044] (4) The hole diameter of the drug ball containing hole is mainly determined according to the diameter of the drug ball.

[0045] (5) The drug ball quantitative transfer device is used with the briquetting machine, and its function is to quickly (in 6-11 seconds) transfer the hundreds of drug balls filled in the drug ball containing holes into each mold hole of the briquetting machine, and ensure that the number of drug balls filled in each mold hole is exactly the same.

[0046] Based on the above, the drug ball quantitative transfer device is manufactured according to the structure of the briquetting machine mold and the size of the drug ball, and it changes with the change of the mold size and the size of the drug ball.

[0047] The following figure description describes the Figure 1 is a photo of the drug ball quantitative transfer device. The basic components of the drug ball quantitative transfer device include (from top to bottom) a ball pressing plate, a ball containing plate, a hole sealing plate and a positioning plate, which will be described below.

[0048] Pressing ball plate: described in the description of the drawings Figure 2 is the photo of pressing ball plate. The main function of pressing ball plate is to press a part of medicine ball into the underlying embedding material. The width and length of pressing ball plate can be put into the ball containing plate plus medicine slot; the lower part of pressing ball plate has a cylinder, which is called pressing ball cylinder, and its specific diameter is 1mm-4mm smaller than the hole diameter of medicine ball containing hole; the head of pressing ball cylinder is inwardly concave arc; the column height is determined according to the sum of the thickness of ball containing plate, positioning plate and positioning cylinder; the number of pressing ball cylinder is the same as the number of mold hole of briquetting machine mold, and the distribution of cylinder is the same as the distribution of mold hole of briquetting machine mold (hole spacing).

[0049] Ball containing plate: described in the description of the drawings Figure 3 is the photo of ball containing plate and sealing hole plate after assembly. The lower part of ball containing plate has a plug-in slot, and the thickness of plug-in slot is slightly larger than the diameter of medicine ball; the depth of plug-in slot is 1.2-2mm, which is the place for the insertion of sealing hole plate; the plug-in slot has the same number of through holes as the number of mold holes of briquetting machine, which is called medicine ball containing hole, and the hole diameter is determined according to the size of medicine ball, and the hole diameter is 1mm to 5mm larger than the diameter of medicine ball; the medicine ball containing hole is a through hole; the distribution of medicine ball containing hole on the ball containing plate is consistent with the distribution of pressing ball cylinder of pressing ball plate, that is, the hole center corresponds to the center of the cylinder; the upper surface of ball containing plate is a medicine adding slot surrounded by four edges, and the height of edge is 20-50mm, which helps to quickly fill medicine ball into medicine ball containing hole.

[0050] Sealing hole plate: stainless steel plate, plate thickness 0.25-2mm; sealing hole plate is inserted into the plug-in slot under the ball containing plate, which can be easily pulled out and inserted from the plug-in slot; when filling medicine ball into medicine ball quantitative transfer device, sealing hole plate is inserted into plug-in slot, which seals all medicine ball containing holes; when transferring medicine ball in medicine ball quantitative transfer device to mold hole of briquetting machine, sealing hole plate needs to be pulled out from plug-in slot, and medicine ball will naturally fall into mold hole of briquetting machine.

[0051] Positioning plate: described in the description of the drawings Figure 4 is the photo of positioning plate. The function of positioning plate is to quickly correspond medicine ball containing hole with mold hole of briquetting machine. The lower part of positioning plate has the same number of square columns or cylinders as the number of mold holes of briquetting machine, which is called positioning column; the height of positioning column is 3-10mm; the positioning column under the positioning plate must correspond to the mold hole of briquetting machine one by one, that is, it can be inserted into the mold hole of briquetting machine one by one; the positioning plate / positioning column has a through positioning hole; the hole diameter of through positioning hole is 1mm-4mm larger than the diameter of medicine ball.

[0052] Ball containing plate and positioning plate are fixed (screwed) together by screws, and can also be bonded together by strong engineering glue, while sealing hole plate and pressing ball plate are movable during the operation of transferring medicine ball.

[0053] The pill quantitative transfer device is not limited to the above structure, and any device or instrument intended to quantitatively transfer the pills into the die hole of the briquetting machine is within the core concept and core technology of the present application. For example, the pill quantitative transfer device can also be composed of three plates, from top to bottom, the ball containing plate, the hole sealing plate and the positioning plate; the pill quantitative transfer device can also be composed of two plates, from top to bottom, the ball containing plate and the hole sealing plate, and the hole sealing plate is inserted into the insertion plate slot with a fixed hole sealing plate structure below the ball containing plate.

[0054] The structure of the pill quantitative transfer device will be further described below by taking the FTLD35-2-10 briquetting machine of Shangqiu Futong Machinery Equipment Co., Ltd. used in the present project as an example.

[0055] When purchasing the FTLD35-2-10 briquetting machine, three sets of molds were selected according to the needs, which are 30x30mm straight edge R3 round corner mold, 12x12mm straight edge R2.5 mold and 18x18mm straight edge R2.5 mold. The structure and use method of the pill quantitative transfer device will be further described below by taking the 18x18mm straight edge R2.5 mold as an example.

[0056] Main parameters of the 18x18mm straight edge R2.5 mold:

[0057] There are 132 square holes distributed on the mold, with a side length of 18mm. The mold is rectangular, with 11 holes in the horizontal direction, a side-to-side distance of 10.0mm, i.e. a center distance of 28.0mm; 12 holes in the vertical direction, a side-to-side distance of 12.0mm, i.e. a center distance of 30.0mm; the hole depth can be adjusted within the range of 100mm (moving the punch up and down in the mold hole).

[0058] The structure of the pill quantitative transfer device matched with the 18x18mm straight edge R2.5 mold is as follows:

[0059] The pill pressing plate is made of PVC plastic plate, with a thickness of 4mm, a width of 298mm and a length of 347mm. There are 132 cylinders distributed in the middle of the lower surface of the plate, with a height of 20-22mm, a diameter of 6-8mm and an inwardly concave arc-shaped head. There are 11 cylinders in the horizontal direction, with a distance (center distance) of 28.0mm; there are 12 cylinders in the vertical direction, with a distance (center distance) of 30.0mm.

[0060] Ball-containing plate: made of PVC transparent plate; plate width 298+20=318mm, plate length 347+20=367mm; the lower surface of the plate has a plate slot, the plate slot is 8mm-10mm thick; the plate slot is 1.5mm deep; the plate slot is 298mm wide and 367mm long; the three edges surrounding the plate slot are 10mm+1.5mm=11.5mm thick; the plate slot is distributed with 132 through holes for containing medicine balls, the hole diameter is 8mm-10mm, the hole depth is 8mm-10mm, the horizontal hole spacing (center distance) is 28.0mm; the vertical hole center distance is 30.0mm; the distribution of the 132 holes in the plate slot is consistent with the distribution of the 132 cylinders of the above-mentioned ball pressing plate, i.e. the 132 cylinders can one-to-one correspond to the through holes for containing medicine balls.

[0061] Hole sealing plate: stainless steel plate, plate thickness 0.7mm, plate width 296mm, plate length 367+100mm; has a handle upwardly turned 20-30mm (convenient for inserting into the plate slot and pulling out of the plate slot).

[0062] Positioning plate: plastic plate (PVC), plate thickness 3-5mm; plate length 367mm, plate width 318mm; the lower surface of the positioning plate has 132 square positioning columns; column height 4-7mm; column edge length 15-16mm; the square positioning column has a through positioning hole in the center, the hole diameter is 8mm-10mm, and the through hole depth is the thickness of the positioning plate + the height of the positioning column.

[0063] As can be seen from the above, the centers of the 132 cylinders of the ball pressing plate, the centers of the 132 through holes of the ball-containing plate, and the centers of the 132 square column holes of the positioning plate are one-to-one corresponding and overlapping, i.e. the 132 cylinders on the ball pressing plate can one-to-one correspond to the 132 through holes of the ball-containing plate and the 132 square column through holes of the positioning plate.

[0064] The ball-containing plate and the positioning plate described above are fixed (screwed) together.

[0065] If each block-shaped composition contains 2 or more medicine balls, 2 or more medicine balls need to be added to each mold hole of the ball pressing machine, and the number of medicine balls contained in each mold hole needs to be the same, which requires the assistance of a medicine ball quantitative dispenser. The medicine ball quantitative dispenser is composed of the above-mentioned ball-containing plate and hole sealing plate.

[0066] The following summarizes the ingredients or substances for preparing medicine balls and embedding materials.

[0067] The substances required for the preparation of the embedding material include animal meat and its processed derivatives, animal organ meat and its processed derivatives, aquatic products such as fish, shrimp, etc. and their processed derivatives, goat milk and its processed derivatives, cow milk and its processed derivatives, milk flavor and its derivatives, meat flavor and its derivatives, yeast and its processed derivatives, sodium chloride, sodium glutamate and its flavoring amino acids, 5'-nucleotides and its flavoring nucleotides, sucrose, sweeteners, grain flour and its processed products, grass powder and its extracts, natural plant powder and its processed products, Maillard reaction products, adhesives such as sodium polyacrylate, preservatives such as sodium diacetate, and the like, which can be used in combination of one or more.

[0068] The preferred substances for the preparation of the embedding material include butter, soybean oil, chicken oil, chicken powder, chicken liver powder, pork liver powder, chicken meat powder and its processed products, fish powder and its processed products, beef powder and its processed products, animal meat and sugar and amino acids Maillard reaction products, peptone, beer yeast powder, sodium chloride, monosodium glutamate, meat flavor (such as commercially available chicken essence), milk powder, yogurt, sucrose, condensed milk paste or powder, cooked rice powder, puffed rice powder and its probiotic fermented products, glutinous rice powder, cooked soybean powder and its probiotic fermented products, puffed soybean meal powder and its fermented products, puffed corn powder and its fermented products, puffed purple rice powder and its fermented products, puffed black bean powder and its fermented products, black sesame powder and its fermented products, grass powder, adhesives such as sodium polyacrylate, preservatives such as sodium diacetate, and the like, which can be used in combination of one or more.

[0069] The auxiliary materials (including coating ingredients) required for the preparation of the drug pellets include fillers, wetting agents, disintegrants, lubricants, and glidants; preferably cooked rice powder, glutinous rice powder, wheat flour, gelatin, agar, xanthan gum, lactose, sucrose, mannitol, sorbitol, starch, dextrin, cyclodextrin, microcrystalline cellulose, trehalose, sodium alginate, chitosan, sodium carboxymethyl cellulose, polyvinyl pyrrolidone, sodium polyacrylate, solid polyethylene glycol, poloxamer, sodium dodecyl sulfate (SDS), benzalkonium, Span 60, carnauba wax, hydrogenated castor oil, glycerol monostearate, paraffin, fatty acid glycerides, sodium carboxymethyl starch, cross-linked povidone, calcium carbonate, sodium bicarbonate, magnesium stearate, talc; drug pellet coating ingredients include cellulose esters (such as cellulose acetate), cellulose acetate phthalate and the like, cellulose ethers (such as ethyl cellulose, hydroxypropyl methyl cellulose, etc.), esters of cellulose ethers, acrylic homopolymers and copolymers (such as polyacrylic acid resins), ethylene polymers (such as povidone, etc.).

[0070] The drugs added for preparing the medicine balls include, but are not limited to, Chinese herbal medicines and extracts thereof, antibacterial drugs, antiviral drugs, antiparasitic drugs, anti-(inflammatory) drugs, drugs for preventing and treating digestive system diseases, drugs for preventing and treating respiratory system diseases, drugs for preventing and treating circulatory system diseases, drugs for preventing and treating urinary system diseases, drugs for preventing and treating nervous system diseases, drugs for preventing and treating nutritional and metabolic diseases, drugs for preventing and treating allergic diseases of animals, drugs for preventing and treating tumors or cancers, drugs for preventing and treating autoimmune diseases or disorders, and antibiotic complexes (i.e., microcapsules, microspheres, solid dispersions or drug-loaded particles containing antibiotics, etc.) that can pass through the rumen of ruminants.

[0071] The selected drugs include selamectin, levamisole and its hydrochloride, ivermectin, sarolaner, doramectin, moxidectin, milbemycin oxime, oxfendazole, fenbendazole, mebendazole, albendazole, oxibendazole, triclabendazole, thiabendazole, thiabenzole, thiabendizole, arecoline hydrobromide, dichlorophenyl dimethyl urea, butamoxifene hydrochloride, praziquantel, epraziquantel, niclosamide, nitroxynil, primaquine phosphate, amprolium, ribavirin, remdesivir, berberine hydrochloride, ampicillin, cefazolin sodium, sulfonamides, sulfadimoxine, sulfadiazine, trimethoprim, sulfisoxazole, sulfamethoxypyridazine, sulfamethoxazole, sulfamonomethoxine, sulfanomonodiazine, terramycin, enrofloxacin, marbofloxacin, lincomycin hydrochloride, neomycin sulfate, thiosulphamethoxazole, erythromycin, roxithromycin, florfenicol, tilmicosin, tylosin fumarate, spectinomycin, lincomycin, amoxicillin, acetaminophen, gitamycin, diazepam, metamizole, furosemide, aspirin, phenobarbital, ethyl piperazine carboxylate, piperazine citrate, hydrochlorothiazide, doxycycline hydrochloride, promethazine hydrochloride, chlorpromazine hydrochloride, clonidine hydrochloride, oxibendazole, aminophylline, betamethasone, nicotinamide, nicotinic acid, naproxen, atropine sulfate, dexamethasone, dexamethasone acetate, prednisone acetate, chlorpheniramine maleate, non-steroidal anti-inflammatory drugs, olaratumab or its veterinary acceptable salts; antibiotic-containing microcapsules, microspheres, solid dispersions that can pass through the rumen of ruminants, or rumen-passing drug-loaded particles composed of antibiotics and excipients that are not degraded in the rumen (antibiotic / excipient complex particles).

[0072] The added bioactive substances include, but are not limited to, natural plants and extracts thereof, medicinal and edible plants and extracts thereof, Chinese herbal medicines and extracts thereof, food and fruit and vegetable and extracts thereof, edible and medicinal fungi and extracts thereof, vitamins, trace elements, functional amino acids, lactic acid bacteria culture, yeast culture, probiotics, prebiotics, postbiotics, medicinal fungus culture of Chinese herbal medicine, biologically active polypeptides and small peptides, biologically active polysaccharides, oligosaccharides; organic small molecules beneficial to animal growth and development and health, such as ingredients with antioxidant and free radical scavenging functions; ingredients with anti-aging, immune-enhancing, cancer-preventing, brain-protecting, heart-protecting, cardio-cerebrovascular-protecting, liver and kidney-protecting, intestinal-protecting, muscle and bone-protecting, and life-extending functions; and nutrients or functional ingredients (such as rumen-passable essential oils) that can pass through the rumen of ruminants.

[0073] Preferably, the active ingredients (substances) added in the drug balls include: purple cone extract, marigold extract, rosemary extract, rose apple extract, grape skin extract, grape seed extract, giant knotweed extract, blueberry extract, tea extract, peptides derived from animals, plants and microorganisms, resveratrol, anthocyanins, astaxanthin, lutein, beta-nicotinamide mononucleotide, vitamin A, vitamin C, vitamin D3, vitamin E, vitamin K2, B vitamins, carnitine, coenzyme Q10, beta-carotene, alpha-lipoic acid, tea polyphenols, sasanqua extract, sasanqua saponin, taurine, glutamine, glutamine dipeptide, hyaluronic acid, glucosamine, chondroitin sulfate, chlorogenic acid, flavonoids, honeysuckle extract, yeast iron, yeast selenium, yeast zinc, yeast cell wall, fungal polysaccharide, spinach powder or extract thereof, active polysaccharides derived from plants or microorganisms, glutathione, inulin, fructooligosaccharide, lactosucrose, raspberry and extract thereof, mannooligosaccharide, chicory powder and extract thereof, cordyceps (fruiting body, mycelium and extract thereof), ganoderma and extract thereof, ganoderma spore powder, shiitake mushroom and extract thereof, hericium and extract thereof, notoginseng extract, notoginseng saponin, andrographis extract, andrographolide, dandelion extract, spilanthes extract, plantain extract, psyllium extract, milk thistle extract, chrysanthemum extract, licorice extract, eucommia and eucommia leaf extract, eucommia leaf microbial culture, radix isatidis extract, radix isatidis extract, radix ophiopogonis and extract thereof, medlar and extract thereof, radix astragali and extract thereof, poria cocos and extract thereof, radix scrophulariae extract, ginkgo biloba extract, thymol, carvacol, cinnamaldehyde, eugenol, soybean lecithin, curcumin, eicosapentaenoic acid EPA, docosahexaenoic acid DHA, arginine, conjugated linoleic acid CLA, whey protein, probiotics, prebiotics, postbiotics; rumen-passable amino acids, rumen-passable vitamins, rumen-passable trace elements, rumen-passable essential oils, rumen-passable organic acids, rumen-passable enzyme preparations, rumen-passable probiotics.

[0074] Example 1 Preparation of bulk composition of praziquantel pellets

[0075] This example uses FTLD 35-2-10 briquetting machine, using 18x18mm straight edge R2.5 mold.

[0076] S1, Preparation of praziquantel pellets:

[0077] a, Preparation of drug-loaded particles: 7 grams of poloxamer P188 was put into a 500ml beaker, melted in a 70°C water bath, 1.4 grams of polyvinylpyrrolidone K20 and 14 grams of praziquantel raw material were added, then 30ml of 98% ethanol was added, slowly stirred, after the material was completely dissolved, 15.12 grams of sodium dodecyl sulfate was added, mixed, then 18 grams of disintegrant was added, stirred and mixed, the beaker was removed from the water bath, continued to stir, when it was still in a softened state, the material was transferred to a laboratory small-scale rotary granulator, extruded and granulated (screen hole 2mm), and the ethanol was volatilized at room temperature; The dry particles were crushed by a pair of roller crushers with a gap of ≦1mm to obtain crushed particles. 1.1% magnesium stearate was added to the crushed particles and mixed evenly to obtain praziquantel particles (drug-loaded particles) for standby;

[0078] b, tabletting: the drug-loaded particles prepared in the above step were tabletted using a laboratory blue tablet press, a spherical punch was selected, the diameter was 7mm, the weight of the spherical tablet was controlled at 372mg-400mg, each tablet contained 93-105mg of praziquantel, the praziquantel spherical tablet obtained by pressing was called a pellet (diameter 7mm, height 6.6-7mm);

[0079] c, coating and dispensing: the pellets were coated with a coating pot; the coating liquid composition: acrylic resin IV 5.1%, hydroxypropyl methyl cellulose 3.0%, PEG60000.7%, talc 1.6%, titanium dioxide 2.4%, magnesium stearate 0.2%, ethanol 73.95%, purified water 13.05%; the temperature of the tablet core was controlled at 33-39°C; the spraying amount of the coating liquid during the coating process was controlled at the maximum amount that did not cause sticking, that is, the tablet core felt slightly wet after spraying the coating liquid, but did not stick; the rotation speed of the coating pot was controlled at 2-5 revolutions per minute, first slow then fast;

[0080] After coating, the pellet dispensing process was entered, 132 pellets were dispensed per bag using an automatic pellet counter, and were ready for use.

[0081] S2, filling pellets:

[0082] Put the sealing plate of the medicine ball quantitative transfer device into the plug-in slot, cover all the 132 medicine ball containing holes, then pour a bag of medicine balls into the medicine ball quantitative transfer device, use the scraper to sweep the medicine balls into the medicine ball containing holes (hole diameter 10 mm, hole depth 10 mm), fill one medicine ball in each hole, after filling the medicine balls, put on the ball pressing plate, get the medicine ball quantitative transfer device loaded with 132 medicine balls, for convenience of description, it is called the medicine ball loaded transfer device, ready for use;

[0083] S3, preparation of embedding material embedding medicine balls:

[0084] a, mix 720 grams of puffed rice powder, 180 grams of self-made chicken meat floss (de-oiled, granular), 100 grams of sucrose, and 120 grams of egg white, granulate with a screw extruder, then treat at 160-180°C for 20-25 minutes (baking and flavoring), crush, and pass through a 30-mesh sieve to obtain a puffed rice powder / meat floss mixture;

[0085] b, take 493 grams of the puffed rice powder / meat floss mixture, 8 grams of xanthan gum, and an appropriate amount of sodium polyacrylate, mix uniformly, then add glycerol and 70 grams of water, stir to soak, add 450 grams of puffed rice powder, 50 grams of beer yeast, 3 grams of sodium chloride, 7 grams of potassium sorbate, and 2 grams of sodium diacetate, mix uniformly to obtain the embedding material, ready for use;

[0086] S4, fill the bottom layer of embedding material into the die hole of the briquetting machine:

[0087] Transfer the embedding material described in step S3 above to the filler hopper of the briquetting machine; start the briquetting machine and fill the embedding material equivalent to 38% of the weight of the block-shaped composition into the die hole of the briquetting machine; after adding the bottom layer of embedding material, lower the punch of the briquetting machine to leave space for adding medicine balls and the upper layer of embedding material, then stop the machine;

[0088] S5, transfer medicine balls:

[0089] In the stopped state, place the medicine ball loaded transfer device obtained in step S2 above on the die of the briquetting machine, pay attention to align it, that is, the 132 square columns (positioning columns, side length 16 mm) with holes (hole diameter 10 mm) on the medicine ball loaded transfer device should all be placed into the 132 die holes (square holes, side length 18 mm) of the briquetting machine; after placing the medicine ball loaded transfer device, pull out the hole sealing plate in the plug-in slot, so that the 132 medicine balls in the medicine ball loaded transfer device fall one by one through the 132 square columns with round holes on the positioning plate and onto the upper layer of embedding material in the 132 die holes of the briquetting machine; then press down the ball pressing plate (cylindrical height 22 mm), slightly press, and then remove the ball pressing plate / medicine ball quantitative transfer device;

[0090] S6, fill the upper layer of embedding material and press:

[0091] Start the briquetting machine to fill the upper layer of embedding material into the briquetting machine mold hole which has been filled with the medicine ball. After the filling is completed, start the extrusion program and begin briquetting. After the upper pressure plate of the briquetting machine is moved to closely contact the surface of the mold and stops moving, the punch in the mold hole moves upward to extrude the material and control the pressure at about 6 tons. After the extrusion is completed, the upper pressure plate is raised and the lower punch is advanced upward to push the formed product out of the mold hole of the briquetting machine to obtain the intermediate product 1.

[0092] S7, drying and oiling of the intermediate product 1:

[0093] Drying the intermediate product 1 at room temperature to obtain the intermediate product 2.

[0094] Coating the surface of the intermediate product 2 with a mixture of butter and soybean oil to obtain the block-shaped composition containing the praziquantel medicine balls.

[0095] From the above preparation process, it can be seen that the accurate range of the praziquantel content in the block-shaped composition is determined by the control of the medicine ball preparation link due to the use of the medicine ball quantitative transfer device, and does not depend on the accuracy of the briquetting of the briquetting machine (the uniformity of the block weight). In other words, the uniformity of the medicine ball weight is controlled by the tablet machine, and then the content of the medicine is controlled within the allowable error range. The main function of the briquetting machine is to complete the process of embedding the medicine balls in the embedding material which is preferred by dogs and cats. The medicine ball quantitative transfer device is used to complete the process of quantitatively and quickly filling the medicine balls into the mold hole of the briquetting machine.

[0096] Preparation of the block-shaped composition containing praziquantel gelatin drop pills in Example 2

[0097] In this example, the FTLD35-2-10 briquetting machine is used, the 18x18mm straight edge R2.5 mold is used, and the medicine ball quantitative transfer device is the same as in Example 1.

[0098] S1, preparation of medicine balls

[0099] Praziquantel / glycerin gelatin medicine balls are prepared by using a drop pill machine.

[0100] Preparation of praziquantel / glycerin gelatin suspension:

[0101] The gelatin is soaked for 3 hours according to the ratio of 1 part of gelatin, 0.45 parts of glycerin and 1.3 parts of water, and then heated to 75-85°C to completely melt the gelatin to obtain a hot glue solution. 179 grams of the hot glue solution is taken, 25 grams of praziquantel fine powder (passed through a 200 mesh sieve) is added, and the mixture is stirred thoroughly to obtain a praziquantel / glycerin gelatin suspension which is kept at 55-65°C for standby use.

[0102] Preparation of praziquantel / glycerin gelatin drop pills (i.e. medicine balls):

[0103] The drop pill machine is a two-drop-head drop pill machine for laboratory use; the distance between the drop pill outlet and the condensate liquid surface is adjusted to 30 mm; the outlet temperature is controlled at 35-45℃; the temperature of the praziquantel / glycerol gelatin suspension is controlled at 55-65℃; the condensate is dimethyl silicone oil with a viscosity of 100 s, and its temperature is controlled at 13-17℃; the drop tube diameter is 6 mm; the drop speed is 70 drops per minute per drop head; the surface of the obtained drop pill is wiped with a rough paper to remove the dimethyl silicone oil; the drop pill moisture content is reduced to 24%-26% at 20-30℃ with air blowing; the prepared drop pill (drug ball) has a diameter of about 7 mm, a weight of about 204 mg, and praziquantel 25 mg per drop pill.

[0104] Sub-packing: The briquetting machine die hole is 132, so each bag is accurately packed with 132 drug balls (drop pills), and the particle counting and packing process is completed by an automatic tablet counter.

[0105] S2-S6 are carried out according to the method of Example 1 to obtain intermediate product 1;

[0106] S7, drying and oiling:

[0107] Intermediate product 1 is dried at 55℃ to obtain intermediate product 2.

[0108] The surface of intermediate product 2 is coated with a mixture of butter / soybean oil to obtain a bulk composition containing praziquantel drug balls (drop pills).

[0109] Example 3 Preparation of bulk composition containing drug balls for dogs and cats

[0110] S1, preparation of drug balls

[0111] The chemical drugs contained in the drug balls and their contents in the drug balls are shown in Table 1; the drug balls have a diameter of 6 mm; the drug balls are compressed by a blue tablet press; when the content of the drug components in the drug balls is less than 20 mg, the weight of the drug balls is controlled at 145 mg; when the content of the drug components in the drug balls is 20-25 mg, the weight of the drug balls is controlled at 180 mg; the main excipients for preparing the drug balls include PEG-6000, poloxamer 188, lactose or sucrose, microcrystalline cellulose, and expanded rice powder.

[0112] Table 1 Drug components and contents in drug balls

[0113] Pill 1: Marbofloxacin 5 mg 10. Ivermectin 0.25 mg Pill 2: Enrofloxacin 5 mg Pill 11: Levamisole hydrochloride 25 mg Pill 3: Doxycycline hydrochloride 10 mg Pill 12: Selamectin 0.3 mg Pill 4: Chlorpheniramine maleate 4 mg Pill 13: Furosemide 20 mg Pill 5: Gitamycin 5 mg Pill 14: Promethazine hydrochloride 12.5 mg Pill 6: Ivermectin 0.25 mg Pill 15: Betamethasone 0.5 mg Pill 7: Fenbendazole 25 mg Pill 14: Dexamethasone acetate 0.75 mg Pill 8: Albendazole 25 mg Pill 15: Prednisone acetate 5 mg Pill 9: Oxfendazole 25 mg Pill 16: Sulfadimethoxine 25 mg

[0114] The drugs listed in Table 1 are described in the relevant content of the First Volume of the Veterinary Pharmacopoeia of the People's Republic of China 2020.

[0115] Preparation steps

[0116] a. Preparation of drug-loaded particles: Poloxamer P188 was placed in a container, PEG6000 was added, and it was melted in a 70°C water bath. The drug was then added, followed by the addition of an appropriate amount of 98% ethanol. The mixture was slowly stirred until the material was completely dissolved or uniformly dispersed. Lactose or sucrose was then added, and the mixture was stirred until it was uniform. The container was removed from the water bath, and stirring was continued until the ethanol evaporated completely. The solidified material was then crushed using a pair of rollers with a gap of ≤1 mm to obtain crushed particles. Magnesium stearate was added to the crushed particles at a concentration of 1.1%, and the mixture was thoroughly mixed to obtain drug-loaded particles, which were ready for use.

[0117] b. Tablet compression: The drug-loaded particles prepared in the previous step were compressed into tablets using a blue tablet press. A spherical punch was selected, with a diameter of 6 mm. The weight of each tablet was controlled to be between 145 mg and 180 mg. The drug content of each tablet is shown in Table 1.

[0118] c. Coating and packaging: The same method as in Example 1 was used.

[0119] The method of Example 1 was followed for S2-S6 to obtain Intermediate 1.

[0120] S7. Drying and oiling of Intermediate 1:

[0121] The Intermediate 1 obtained in step S6 was dried at 60°C to obtain Intermediate 2.

[0122] A mixture of yellow oil / soybean oil was applied to the surface of Intermediate 2 to obtain a block-shaped composition for pets containing the drugs listed in Table 1.

[0123] Example 4: Preparation of a block-shaped composition containing drug balls for pigs, cattle, and sheep

[0124] S1. Preparation of drug balls

[0125] The drug content and concentration in the drug balls are shown in Table 2. The drug balls were prepared in two sizes: 6 mm and 8 mm in diameter. The drug balls were compressed using a blue tablet press. When the drug content in the drug balls was less than 25 mg, the weight of the drug balls was controlled to be 145 mg. When the drug content in the drug balls was greater than 25 mg, the weight of the drug balls was controlled to be between 268 mg and 400 mg. The main excipients used to prepare the drug balls included PEG-6000, poloxamer 188, lactose or sucrose, microcrystalline cellulose, and expanded rice flour.

[0126] Table 2: Drug components and their concentrations in the drug balls

[0127] Pill 1, Terramycin 50 mg Pill 10, Phenobarbital 15 mg Pill 2, Marbofloxacin 20 mg Pill 11, Ketoprofen 100 mg Pill 3, Doxycycline hydrochloride 100 mg Pill 12, Oxibendazole 50 mg Pill 4, Lincomycin hydrochloride 25 mg Pill 13, Naproxen 100 mg Pill 5, Gitamycin 100 mg Pill 14, Betamethasone 0.5 mg Pill 6, Ivermectin 7.5 mg Pill 15, Dexamethasone acetate 0.75 mg Pill 7, Fenbendazole 100 mg Pill 16, Prednisone acetate 5 mg Pill 8, Berberine hydrochloride 100 mg Pill 17, Ethylated 50 mg Pill 9, Sulfadimethoxine 25 mg Pill 18, Aminophylline 50 mg

[0128] The drugs listed in Table 2 are included in the "Veterinary Pharmacopoeia of the People's Republic of China" 2020 Part I.

[0129] Preparation steps

[0130] a. Preparation of drug-loaded particles: Poloxamer P188 was put into a container, PEG6000 was added, and the mixture was melted in a water bath at 70°C. Then the drug was added, followed by the addition of an appropriate amount of 98% ethanol. The mixture was slowly stirred until the drug was dissolved or dispersed uniformly. Then lactose or sucrose was added, followed by the addition of puffed rice powder and microcrystalline cellulose. The container was removed from the water bath, and the stirring was continued until the ethanol was completely volatilized. The dried solidified material was crushed by a roll crusher to obtain crushed material. Then 1.1% magnesium stearate was added to the crushed material and mixed uniformly to obtain drug-loaded particles, which were ready for use.

[0131] b. Tabletting and packaging of drug balls: The drug-loaded particles prepared in the above step were tabletted by using a blue tablet press. Arc-shaped punches were selected, and the drug content in the drug balls was shown in Table 2. Then the drug balls were packaged, with 132 drug balls in each bag, which were ready for use.

[0132] S2. Filling of drug balls:

[0133] 8mm diameter drug balls were selected to have a drug ball containing hole with a diameter of 10mm and a depth of 10mm. 6mm diameter drug balls were selected to have a drug ball containing hole with a diameter of 8mm and a depth of 8mm. The filling of drug balls was carried out according to the method of Example 1.

[0134] S3. Preparation of embedding material for embedding drug balls:

[0135] a. 400g puffed rice powder, 200g fried soybean powder, 400g fried corn powder, and 100g sucrose were mixed and roasted at 160°C for 20 minutes to obtain a mixture with a strong rice flavor.

[0136] b. 450g of the above mixture, 10g of xanthan gum, 90g of glycerol and water were mixed uniformly, and then fully stirred and soaked. Then 500g of the above mixture and 9g of sodium diacetate were added and stirred uniformly to obtain embedding material suitable for pigs, cattle, and sheep to take actively, which was ready for use.

[0137] S4-S6 were carried out according to the method of Example 1 to obtain intermediate product 1.

[0138] S7. Drying:

[0139] Intermediate product 1 was dried at room temperature or 55-60°C to obtain a block-shaped composition containing drugs, which was edible for pigs, cattle, and sheep.

[0140] Example 5 Preparation of a block-shaped composition containing plant extracts

[0141] S1. Preparation of drug balls

[0142] Plant extracts can be used as functional ingredients for the preparation of health snacks for pets such as dogs and cats. However, most plant extracts have bitter taste and pets will not eat them without treatment. The present invention provides a method for preparing small medicine balls from plant extracts, coating the medicine balls, and embedding the coated medicine balls in a pet-acceptable embedding material to prepare pet-acceptable oral block compositions.

[0143] This example illustrates the preparation of 24 medicine balls (Table 3 below) from 23 plant extracts and cordyceps sinensis, and the preparation of 24 block compositions containing different active ingredients by embedding the medicine balls in an embedding material. The medicine balls described in this example have a diameter of 8 mm and a weight of 380-450 mg. The main excipients used for the preparation of the medicine balls include PEG-6000, lactose or sucrose, microcrystalline cellulose, β-cyclodextrin, starch, puffed rice powder, magnesium stearate, etc. The medicine balls are prepared by using a blue tablet press. The active ingredient content of the 24 medicine balls is shown in Table 3.

[0144] Table 3 Active ingredient content of medicine balls

[0145] Pill 1, Panax notoginseng saponins 50 mg Pill 13, Anemarrhena asphodeloides extract 25 mg Pill 2, Astragalus membranaceus extract 200 mg Pill 14, Eucommia ulmoides extract 50 mg Pill 3, Isatis indigotica root extract 100 mg Pill 15, Fructus lycii extract 50 mg Pill 4, Cordyceps sinensis mycelium 150 mg Pill 16, Herba epimedii extract 25 mg Pill 5, Scutellaria baicalensis extract 50 mg Pill 17, Fructus corni extract 100 mg Pill 6, Yucca schidigera extract 50 mg, chrysanthemum powder 100 mg Pill 18, Radix codonopsis extract 150 mg Pill 7, Lonicera japonica extract 100 mg Pill 19, Schisandra chinensis extract 100 mg Pill 8, Plantago asiatica extract 100 mg Pill 20, Ligustri lucidi fructus extract 200 mg Pill 9, Asparagus racemosus extract 50 mg Pill 21, Echinacea purpurea extract 100 mg Pill 10, Cichorium intybus extract 100 mg Pill 22, Rosmarinus officinalis extract 50 mg Pill 11, Taraxacum mongolicum extract 100 mg Pill 23, Origanum vulgare volatile oil 20 mg Pill 12, Poria cocos extract 100 mg Pill 24, Rhizoma coptidis extract 50 mg

[0146] S1, Preparation of medicine balls

[0147] (1) Preparation of drug-loaded particles containing rosemary extract and oregano oil: PEG6000 is melted in a 70°C water bath, rosemary extract or oregano oil is added, and the mixture is stirred until uniform. Hot corn cob powder is then added, and the mixture is stirred until uniform. After cooling and solidification, mannitol and microcrystalline cellulose are added, and the mixture is stirred until uniform. 1.1% magnesium stearate is added, and the mixture is stirred until uniform to obtain drug-loaded particles for use.

[0148] (2) Preparation of drug-loaded particles containing ligustrum lucidum extract and echinacea extract: The extract is concentrated under reduced pressure to a thick paste. Mannitol, sucrose, and microcrystalline cellulose are added, and the mixture is stirred until uniform. The mixture is granulated, dried, and sieved through a 20-mesh screen. 1.1% magnesium stearate is added, and the mixture is stirred until uniform to obtain drug-loaded particles for use.

[0149] (3) Preparation of drug-loaded particles of other active ingredients described in Table 3: PEG6000 is placed in a container and melted in a 70°C water bath. The drug is added, followed by an appropriate amount of 98% ethanol. The mixture is slowly stirred until the drug is uniformly dispersed. β-cyclodextrin is then added, and the mixture is stirred until uniform. Microcrystalline cellulose and mannitol are added, and the mixture is stirred until uniform. The container is removed from the water bath, and the mixture is continuously stirred until the ethanol is completely volatilized. The solidified material is crushed through a gap of 0.7-1 mm using a pair of roller crushers to obtain crushed material. 1.1% magnesium stearate is added to the crushed material, and the mixture is stirred until uniform to obtain drug-loaded particles for use.

[0150] (4) Tablet compression: The drug-loaded particles prepared in the above step are compressed into tablets using a blue tablet press. A spherical punch is selected, and the diameter is 6 mm. The weight of each spherical tablet is controlled at 180 mg. The drug content of each tablet is shown in Table 3.

[0151] (5) Coating, dispensing: same as Example 1.

[0152] S2-S6 were carried out according to the method of Example 1 to obtain intermediate product 1;

[0153] S7, drying, oiling:

[0154] Intermediate product 1 was dried at room temperature, and then a mixture of butter and soybean oil was coated on the surface of intermediate product 1 to obtain a block composition edible for dogs and cats containing natural plant extracts.

[0155] Example 6 Preparation of a block composition containing refined plant extracts and nutrients

[0156] S1, preparation of drug pellets

[0157] Fourteen drug pellets containing different active ingredients are shown in Table 4; the main excipients for preparing the drug pellets include β-cyclodextrin, lactose, poloxamer 188, and microcrystalline cellulose; the diameter of the drug pellets is 8 mm, and the weight of the drug pellets is 280-400 mg; the drug pellets were compressed using a blue tablet press.

[0158] Table 4 Active ingredient content in drug pellets

[0159]

[0160]

[0161] Drug pellet preparation steps

[0162] a, granulation: poloxamer P188 was put into a container and melted in a water bath at 70°C, then the drug was added, followed by the addition of an appropriate amount of 98% ethanol, slow stirring, and then the addition of β-cyclodextrin after the material was basically dissolved or uniformly dispersed, followed by the addition of lactose powder, stirring and mixing, removing the container from the water bath, and continuing to stir and dry at room temperature to volatilize the ethanol; the solidified material after volatilization of the ethanol was crushed using a roll crusher to obtain crushed material, 1.1% magnesium stearate was added to the crushed material and mixed uniformly to obtain drug-loaded granules for use;

[0163] b, tabletting: the drug-loaded granules prepared in the previous step were tabletted using a blue tablet press, a spherical punch was selected, the diameter was 6 mm or 8 mm, the weight of the spherical tablets was controlled to be 180 mg-360 mg, and fourteen drug pellets containing different active ingredients were listed in Table 4;

[0164] c, coating, dispensing: same as Example 1;

[0165] S2-S6 were carried out according to the method of Example 1 to obtain intermediate product 1;

[0166] S7, drying, oiling:

[0167] The intermediate product 1 is dried at room temperature or 55-60°C, then a butter / soybean oil mixture is coated on the surface of the intermediate product 1 to obtain a dog and cat edible block composition containing refined plant extracts

[0168] Example 7 Block composition containing vitamin and other nutrient ingredients

[0169] S1, Preparation of drug pellets

[0170] The active ingredient content of the drug pellets is shown in Table 5; the main excipients for preparing the drug pellets include β-cyclodextrin, lactose, poloxamer P188 (hereinafter referred to as P188); the diameter of the drug pellets is 6 mm, and the weight of the drug pellets is 180 mg; and the drug pellets are compressed by using a blue tablet press.

[0171] Table 5 Content of each nutrient component in the drug pellets and the amount of raw materials

[0172]

[0173]

[0174] Preparation steps

[0175] a, Granulation: P188 is put into a container and melted in a water bath at 70°C, the active ingredient is added, and slowly stirred until uniformly dispersed, then lactose and β-cyclodextrin are added and stirred until uniformly mixed, the container is removed from the water bath, and stirring is continued until completely solidified; the solidified granules are crushed by a pair of roller crushers to obtain crushed material, 0.8% magnesium stearate is added to the crushed material and mixed to obtain drug-loaded granules, which are ready for use;

[0176] b, Tablet compression: the drug-loaded granules prepared in the above step are compressed by using a blue tablet press, a spherical die is selected, the diameter is 6 mm, and the weight of the spherical tablets is controlled at 180 mg, the content of each nutrient in the drug pellets is shown in Table 5;

[0177] c, Coating and packaging: the same as in Example 1;

[0178] S2-S6 are carried out according to the method of Example 1 to obtain intermediate product 1;

[0179] S7, Drying and oil coating

[0180] The intermediate product 1 is dried at 60°C, then a butter / soybean oil mixture is coated on the surface of the intermediate product 1 to obtain a dog and cat edible block composition containing vitamins and other nutrient ingredients.

[0181] Example 8 Preparation of a block composition containing praziquantel pills

[0182] This example describes the preparation of pills (i.e. boluses) containing praziquantel using a Chinese medicine pill-making machine. The pills are then coated, and the coated pills are then embedded in edible material for dogs and cats, thereby obtaining a block composition of praziquantel boluses with good taste masking. The preparation points are briefly described below.

[0183] (1) This example uses the FTLD35-2-10 briquetting machine of Shangqiu Futong Machinery Equipment Co., Ltd., with a 18x18mm straight edge R2.5 mold;

[0184] (2) This experiment uses three types of bolus quantitative transfer devices, and the diameters of the bolus containing holes of the three types of bolus quantitative transfer devices are 6mm, 7mm and 8mm, respectively, and the diameters of the 132 cylinders of the corresponding ball pressing plate are 4.5mm, 5.5mm and 6.5mm, respectively; the structure of the other parts of the bolus quantitative transfer device is the same as that of the bolus quantitative transfer device described in Example 1;

[0185] (3) Three different hole diameters of the quantitative transfer device are suitable for three types of bolus, which are: 4mm diameter bolus containing 10mg of praziquantel; 5mm diameter bolus containing 20mg of praziquantel; 6mm diameter bolus containing 30mg of praziquantel;

[0186] (4) The main excipients used to prepare the above three types of bolus with different diameters and different praziquantel contents are: rice powder, starch, and a mixture of sticky rice powder, with the addition of an appropriate amount of binder (xanthan gum and sodium polyacrylate); wetting agent: water, glycerol, 95% ethanol;

[0187] (5) The pill preparation uses the HK-92Z full-automatic pill-making machine of Guangzhou Xulong Machinery Equipment Co., Ltd.;

[0188] (6) The three types of bolus are all coated, and the composition of the coating liquid and the main operation steps are the same as described in Example 1;

[0189] The other operation processes related to Example 1 are the same, and therefore will not be described in detail.

[0190] Through the above process, a block composition of praziquantel pills (boluses) can be prepared, with specifications of: praziquantel 10mg per block composition; praziquantel 20mg per block composition; praziquantel 30mg per block composition.

[0191] Example 9 Block composition of probiotic bolus for dogs and cats

[0192] The probiotic bacteria are mixed with excipients (such as trehalose, lactose, skim milk powder, microcrystalline cellulose, mannitol, etc.), and a blue tablet press (ball) machine is used to press the mixture into spherical tablets, which are called bacterial balls. Then, the bacterial balls are coated at 33-36°C. Embedding materials are prepared according to the tastes preferred by different animals. The bacterial balls are embedded using a briquetting machine and a drug ball quantitative transfer device, i.e., the bacterial balls are pressed into block-shaped compositions that are preferred by animals. The compositions have the following prominent features: (1) the survival rate of lactic acid bacteria during storage is significantly improved (increased by more than 65%), the storage period is significantly prolonged (up to 2.5 years), and the gastric acid resistance and bile resistance of the lactic acid bacteria product are improved; (2) the active feeding rate of animals is improved; and (3) feeding is convenient.

[0193] In this embodiment, an FTLD35-2-10 briquetting machine from Shangqiu Futong Machinery Equipment Co., Ltd. is used, and a 18x18 mm straight edge R2.5 mold is used.

[0194] The drug ball quantitative transfer device is made according to the mold of the briquetting machine. The preparation steps are as follows:

[0195] S1, preparation of bacterial balls

[0196] a, tablet pressing: 100 g of mixed probiotic powder (containing 500 billion CFU / g of animal bifidobacterium, lactobacillus acidophilus, lactobacillus casei, bacillus subtilis) (lyophilized granules) is added to a mixture of inulin, fructooligosaccharide, lactose (granular type), trehalose, mannitol, and microcrystalline cellulose 300 g, mixed uniformly, and dry-pressed (using a blue tablet press) to select a spherical die with a diameter of 8 mm, and the weight of the spherical tablets is controlled to be 390-420 mg, each tablet containing 487-525 billion CFU of probiotic bacteria. The pressed spherical tablets containing probiotic bacteria are called bacterial balls (diameter 8 mm, height 6.8-7.6 mm).

[0197] b, coating: the same as in Example 1;

[0198] S2-S6 are performed according to the method of Example 1 to obtain intermediate product 1.

[0199] S7, drying and oiling of intermediate product 1

[0200] Drying at room temperature for 8 hours gives intermediate product 2.

[0201] A mixture of yellow oil / soybean oil is applied to the surface of intermediate product 2 to obtain a block-shaped composition containing probiotic bacterial balls.

[0202] Example 10: block-shaped composition containing probiotic bacterial balls

[0203] The preparation process and operation of this example are the same as those of Example 1 except that the composition of the bolus is different from that of the above-mentioned examples. Therefore, the following mainly introduces the preparation of the over-rumen bolus, coating of the bolus and preparation of the embedding material, and the other preparation processes are not described.

[0204] 1. Preparation of bolus containing over-rumen vitamin

[0205] The boluses containing different vitamins are numbered respectively, and the specific components are shown in Table 6.

[0206] Table 6 Components of bolus 1 to bolus 7

[0207]

[0208] Preparation process of bolus 1: According to the weight ratio, commercially available over-rumen vitamin A microcapsules 200 parts (VA 60,000 units / g), lactose (granular type) 200 parts, and magnesium stearate 4.5 parts are uniformly mixed, and then tableted by using a tablet press with a pressure of about 4.5 tons, a nearly spherical punch, and a diameter of 8 mm, and the weight of the bolus is 410 mg.

[0209] Preparation process of bolus 2: Wax pellets are first prepared by using a spray condensation method, then an anti-adhesion agent is added, and the mixture is uniformly mixed and then pressed into a ball. Hydrogenated castor oil 50 parts and monoglyceride 160 parts are put into a melting tank and melted at about 85°C, then silica 80 parts is added and uniformly mixed, and then the material temperature is reduced to 65-68°C, commercially available VA 100 parts (500,000 IU / g) is added, uniformly mixed, and maintained at 65°C, sprayed through a high-pressure nozzle, the diameter of the wax pellets is controlled to be 0.6-1.1 mm, the temperature of the material receiving chamber (tank) is maintained at 15-21°C, and VA-containing wax pellets are obtained; 390 parts of the wax pellets and magnesium stearate 4.5 parts are uniformly mixed, and then tableted by using a tablet press with a pressure of about 4.5 tons, a nearly spherical punch, and a diameter of 8 mm, and the weight of the bolus is controlled to be about 390 mg, and over-rumen bolus containing VA 50,000 units per pellet is obtained.

[0210] Preparation process of bolus 3: Wax pellets are first prepared by using a spray condensation method, then an anti-adhesion agent is added, and the mixture is uniformly mixed and then pressed into a ball. Nicotinic acid is first dissolved in an appropriate amount of ethanol, silica is added, uniformly mixed, and dried under reduced pressure to remove ethanol, and drug-loaded granules are obtained for standby use; hydrogenated castor oil and monoglyceride are put into a melting tank and melted at about 85°C, then the material temperature is reduced to 65-68°C, the drug-loaded granules are added, uniformly mixed, and maintained at 65°C, sprayed through a high-pressure nozzle, the diameter of the wax pellets is controlled to be 0.6-1.1 mm, the temperature of the material receiving chamber (tank) is maintained at 15-21°C, and VA-containing wax pellets are obtained; 400 parts of the wax pellets and magnesium stearate 4.5 parts are uniformly mixed, and then tableted by using a tablet press with a pressure of about 4.5 tons, a nearly spherical punch, and a diameter of 8 mm, and the weight of the bolus is controlled to be about 390-420 mg, and over-rumen bolus containing nicotinic acid 150 mg per pellet is obtained.

[0211] Process of preparing drug pellet 4: by weight, commercially available over the rumen vitamin E wax pill (50%) 300 parts, microcrystalline cellulose 100 parts, magnesium stearate 4.5 parts, mix evenly, tablet under the pressure of about 4.5 tons, near spherical punch, diameter 8 mm, drug ball weight about 387 mg.

[0212] Process of preparing drug pellet 5: using rotary pressure granulator, then add anti-sticking agent, mix evenly and then press the ball. First, dissolve nicotinic acid with appropriate amount of ethanol, add silica, mix evenly, dry under reduced pressure, remove ethanol, get drug-loaded granules, ready for use; Put monoglyceride into the melting tank, melt at about 85°C, then reduce the material temperature to 65-68°C, add drug-loaded granules, mix evenly, continue to cool the material to 45°C, select 0.7 mm sieve plate, use rotary pressure granulator to extrude granulation, extruded granules are solidified below 15°C, obtain drug-loaded granules containing nicotinic acid; Take 380 parts of drug-loaded granules and magnesium stearate 4.5 parts, mix evenly, tablet under the pressure of about 4.5 tons, die punch near spherical, diameter 8 mm, control the weight of drug ball about 390 mg, get nicotinic acid 200 mg / 390 mg of rumen-passable drug ball.

[0213] Process of preparing drug pellet 6: first mix vitamin, PVP and microcrystalline cellulose evenly, add appropriate amount of ethanol to wet, dry, get the mixture; Mix the mixture with monoglyceride microspheres (diameter 0.3-0.5 mm) and magnesium stearate (1.5% of total weight), mix evenly, tablet under the pressure of about 6 tons, die punch near spherical, diameter 8 mm, control the weight of drug ball about 390 mg, get drug ball containing VA60000 IU, VE100 mg, VD330000, nicotinic acid 100 mg, biotin 0.5 mg / 390 mg.

[0214] 2, drug ball coating

[0215] Coating equipment is coating pan, use acid-soluble coating material to coat the above vitamin-containing drug ball (drug ball 7 is soft capsule, directly coated). Coating liquid composition and process control: acrylic resin IV 7.2%, hydroxypropyl methyl cellulose 1.0%, PEG60000.7%, talc 1.6%, magnesium stearate 0.2%, ethanol 74%, purified water 13%; The temperature of the tablet core is controlled at 33-39°C; The coating process controls the spraying amount of the coating liquid to the maximum amount that does not cause sticking, that is, the tablet core feels wet after spraying the coating liquid, but does not stick; The rotation speed of the coating pan is controlled at 2-5 revolutions per minute, first slow and then fast, the coating weight gain is controlled at 12%-16%.

[0216] The acrylic resin IV is not soluble at pH 5 or above, and is soluble at pH 3. The rumen pH fluctuates between 5.4 and 7.5, and is usually above 6.2. The test shows that the coating layer of the above-mentioned medicine ball is completely dissolved in about 17 minutes in a pH 3.8 buffer solution, and the surface of the medicine ball swells in a pH 6.2 buffer solution without dissolution and film peeling.

[0217] 3. Embedding material

[0218] The coated medicine ball is embedded in food that is preferred by ruminants to form a block-shaped composition. The preferred embedding material is prepared by mixing puffed rice powder, puffed corn powder, alfalfa powder, and xanthan gum, and the wetting agent is a mixture of ethanol, glycerol, and water.

[0219] Example 11: Block-shaped composition containing a post-ruminal antibacterial drug

[0220] 1. Preparation of medicine ball containing a post-ruminal antibacterial drug

[0221] The medicine balls containing different antibacterial drugs are numbered, and the specific ingredients are shown in Table 7.

[0222] Table 7: Ingredients of medicine ball 1 to medicine ball 5

[0223] Pill No. Active ingredient content Pill 1 Doxycycline 100 mg; monoglyceride 200 mg; pill weight 310 mg Pill 2 Enrofloxacin 50 mg; pill weight 300 mg Pill 3 Terramycin 100 mg; pill weight 400 mg Pill 4 Containing Rhizoma coptidis extract 200 mg Pill 5 Containing commercially available 15% terramycin microcapsules 250 mg

[0224] Preparation process of medicine ball 1: spray condensation method is used to prepare wax pellets first, then add antiblocking agent, mix evenly and press into balls.(1) Put monoglyceride into the melting tank, melt at about 75°C, then reduce the material temperature to 65-68°C, add doxycycline (purity above 95%) and mix evenly, keep the material temperature at 65°C, spray through high-pressure nozzle, control the diameter of wax pellets at 0.6-1.1mm, and the material receiving room (tank) temperature is kept at 15-21°C, to obtain wax pellets containing doxycycline;(2) Take 305 parts of wax pellets and 4.5 parts of magnesium stearate, mix evenly, use ordinary tablet press at a pressure of about 4.5 tons, the die punch is nearly spherical, the diameter is 8mm, control the weight of the medicine ball to be about 310mg, obtain medicine ball containing 100mg post-ruminal doxycycline per pill.

[0225] Drug pellet 2 preparation process: microcapsules were prepared by using fluidized bed granulator and coating machine, and then the microcapsules were pressed into drug pellets. Drug-containing pellet core preparation: (1) blank pellet core was sucrose pellet core (0.7-0.9 mm), enrofloxacin was dispersed in 2% PVP binder, the blank pellet core was preheated to 40°C, and the drug was added in the fluidized bed by using the optimized process parameters, and the unqualified drug-containing pellet core was removed through 24 mesh sieve, and the drug loading of the pellet core was determined to be 69%; (2) fluidized bed coating: the coating liquid for coating the drug-containing pellet core was 7.2% acrylic resin IV in 85% ethanol solution, the air blowing frequency (HZ) was 20-25, the coating temperature (°C) was 28-33, the coating liquid flow rate (ml.min) was 0.8-1.3, and the atomization pressure (kg / cm2) was 0.1-0.2; under the above conditions, the microcapsules containing enrofloxacin 53.6% were prepared; (3) 1 part of the microcapsules was mixed with about 2 parts of monoglyceride microspheres and magnesium stearate (1% of the total amount), and directly compressed into spherical tablets, the spherical tablets had a diameter of 7 mm and a weight of about 300 mg, and contained enrofloxacin 51-53 mg / tablet; (4) the spherical tablets were coated with a coating pot using 7.2% acrylic resin IV as the coating liquid (the coating parameters are described in detail in the other examples above), and the coating weight gain was 13-16%, thereby obtaining the drug pellets containing the rumen bypass enrofloxacin (50 mg / tablet).

[0226] Drug pellet 3 preparation process: micro-pellet cores were prepared by using an extruder and a rounding machine, and then the micro-pellets were coated by using 7.2% acrylic resin IV as the coating liquid by bottom spraying in a fluidized bed, thereby obtaining the micro-pellets containing aureomycin; the micro-pellets were mixed with monoglyceride microspheres and magnesium stearate, and then compressed into spherical tablets; the spherical tablets were coated with 7.2% acrylic resin IV as the coating liquid, thereby obtaining the drug pellets containing the rumen bypass aureomycin. Main process parameters and operation process: (1) aureomycin, microcrystalline cellulose and polyethylene glycol 6000 were weighed according to the optimal prescription ratio, mixed uniformly, heated to 70°C, added with appropriate amount of ethanol, mixed uniformly, and then put into a screw extruder, and extruded into a strip (extruder screen plate aperture 0.7 mm, extrusion speed 28-32 HZ); the extruded strip was placed in a rounding machine, the temperature was controlled at 36-45°C, and the rounding speed and rounding time were adjusted (rounding speed 43-48 HZ, rounding time 5-8 min), so that the rounding was complete, the micro-pellets were taken out and dried under reduced pressure for 5-6 hours at 25-33°C, and then sieved, thereby obtaining 20-40 mesh micro-pellet cores; (2) 7.2% acrylic resin IV was used as the coating liquid to perform bottom spraying in a fluidized bed, and the main parameters of the coating process were as follows: air inlet pressure 0.2-0.26 bar, air inlet temperature 34-39°C, and coating weight gain 12%-15%, thereby obtaining the rumen bypass aureomycin micro-pellets; (3) the micro-pellets were mixed with monoglyceride microspheres and magnesium stearate, and then compressed into spherical tablets; (4) the spherical tablets were coated with a coating pot using 7.2% acrylic resin IV as the coating liquid (the coating parameters are described in detail in the other examples above), thereby obtaining the drug pellets containing the rumen bypass aureomycin.

[0227] Preparation of drug pellet 4: The drug was granulated by using a rotary pressure granulator, then anti-sticking agent was added, and the mixture was uniformly compressed into pellets. First, 10 parts of the extract of Coptis chinensis was mixed with 4 parts of polyethylene glycol 6000, and heated at 70°C. When the temperature of the material reached 65°C, the heating was continued for 5-8 minutes. Then, an appropriate amount of ethanol was added, and the material was cooled to 45°C. The material was extruded and granulated by using a rotary pressure granulator with a screen plate of 0.6-0.7 mm. The extruded granules were solidified at a temperature below 15°C, and dried to remove the ethanol completely. Thus, drug-loaded granules containing the extract of Coptis chinensis were obtained. Then, 380 parts of the drug-loaded granules and 4.5 parts of magnesium stearate were mixed, and the mixture was compressed into tablets by using a tablet press. The tablets were punched into nearly spherical shape with a diameter of 8 mm and a weight of about 390 mg. The tablets were compressed under a pressure of about 4.5 tons. Thus, spherical tablets containing the extract of Coptis chinensis were obtained. The spherical tablets were coated with a coating liquid containing 7.2% of acrylic resin IV by using a coating kettle. The weight of the coating was increased by 13-15%. Thus, drug pellets containing the extract of Coptis chinensis which can pass through the rumen were obtained.

[0228] Preparation of drug pellet 5: commercially available 15% aureomycin microcapsules were mixed with monoglyceride microspheres (0.3-0.5 mm in diameter) and magnesium stearate (1.5% of the total weight). The mixture was compressed into tablets by using a tablet press. The tablets were punched into nearly spherical shape with a diameter of 8 mm and a weight of about 350 mg. The tablets were compressed under a pressure of about 6 tons. Thus, spherical tablets containing 37.5% of aureomycin were obtained. The spherical tablets were coated with a coating liquid containing 7.2% of acrylic resin IV by using a coating kettle. Thus, drug pellets containing aureomycin which can pass through the rumen were obtained.

[0229] 2. Embedding material

[0230] The coated drug pellets were embedded in food which is preferred by ruminants to form a block-shaped composition. The preferred embedding material was prepared by mixing puffed rice powder, puffed corn powder, alfalfa powder and xanthan gum. The wetting agent was a mixture of ethanol, glycerol and water.

[0231] This example is different from the above-described examples in the composition of the drug pellets. The preparation process and operation of this example were the same as those of example 1. Therefore, the preparation process is not repeated.

[0232] Test of the feeding stimulating effect of the block-shaped composition described in example 1

[0233] I. Test of the feeding stimulating effect of the block-shaped composition described in example 1

[0234] The block composition containing praziquantel pellets described in Example 1 was used as the test product, and the baiting effect test was conducted on 75 rural guard dogs in different places (Xinjiang, Inner Mongolia, etc.) at different times. The dogs were fasted overnight and then fed with the block composition containing praziquantel pellets described in Example 1, one piece per dog. Of the 75 dogs, 68 voluntarily ate the composition in the first feeding, and none of them vomited the composition. Four dogs ate the composition in the second feeding, and three dogs vomited the composition after eating it. The voluntary eating rate of the test product was 90.67% according to the calculation.

[0235] The baiting effect test of the commercially available related product (praziquantel chewable tablets) was conducted on the 75 dogs using the same method 19-31 days before the test product was fed. The results showed that the voluntary eating rate was 48.6%.

[0236] II. Baiting effect test of the block composition containing praziquantel pellets described in Example 2

[0237] The block composition containing praziquantel pellets described in Example 2 was used as the test product, and the baiting effect test was conducted on 47 dogs (mainly rural guard dogs) in Xinjiang, Inner Mongolia, etc. at different times. The dogs were fasted overnight and then fed with the block composition containing praziquantel pellets, one piece per dog. None of the 47 dogs refused to eat in the first feeding, and 44 of them ate the composition in the second feeding 36 days later, with an eating rate of 93.62%. Therefore, it is a promising new animal preparation in the field of animal health to first make gelatin pellets of the drug and then embed them in edible embedding material to form a block composition.

[0238] III. Eating effect test of the block composition described in Example 3

[0239] The five block compositions containing drug pellets in Table 1 of Example 3 (see Table 1-1 below) were used as the test products, and the eating effect test was conducted on pet dogs and cats. The test was conducted in five pet hospitals in Beijing and Hubei, with one test product tested in each pet hospital. The test product was placed in the food bowl in the cage, and the eating behavior was observed. The test results are summarized in Table 1-1 below.

[0240] Using the same test method, the dogs and cats participating in the test were first fed with commercially available tablets containing the same drug ingredients before the test product was fed. The test results showed that none of the dogs and cats ate the commercially available tablets (see Table 1-2 below).

[0241] Table 1-1 Eating effect test of five block compositions on dogs and cats

[0242]

[0243] Table 1-2 Dog and cat feeding effect test of five kinds of control tablets

[0244]

[0245] Four, the feeding effect test of the block composition described in Example 4

[0246] Five kinds of commercially available tablets (see Table 2-1 below) were used as control products, and five kinds of ball-containing block compositions described in Example 4 were used as test products (see Table 2-1 below). Active feeding effect tests were carried out on pigs (empty sows), beef cattle, and sheep in different places in Hebei and Hubei.

[0247] Table 2-15 kinds of test products (ball-containing block compositions) and 5 kinds of control products (commercially available tablets)

[0248]

[0249] The test results showed that: (1) 23 empty sows (fed with marbofloxacin tablets, doxycycline hydrochloride tablets, and berberine hydrochloride tablets), 27 beef cattle (fed with oxibendazole tablets and naproxen tablets), and 30 sheep (fed with oxibendazole tablets) did not have active feeding behavior on the above-mentioned commercially available control tablets; (2) the animals fed with control products were fed with test products (same active ingredients) in the same feeding manner, and the results showed that the feeding rate reached 80%-92% (80% for sows, 92% for cattle, and 84% for sheep).

[0250] Therefore, by first preparing the drug into a drug ball and then embedding it in food that pigs, cattle, and sheep love to eat (i.e., into a block composition), the problem of feeding pigs, cattle, and sheep with medicine can be solved, which is particularly suitable (convenient) for pigs (such as pregnant sows), cattle, and sheep in a limited feeding environment, and the dosage is accurate, and the stress reaction caused by conventional drug administration is overcome.

[0251] Five, the feeding effect test of the block composition described in Example 5

[0252] The notoginseng total saponins, cat grass extract, and coptis extract described in Table 3 of Example 5 are very bitter active ingredients. Tablets prepared by conventional methods are not eaten by dogs and cats, and even if meat floss and other substances are added, the feeding rate is below 35% (see Table 3-2 below). If they are first prepared into drug balls, then coated, and then embedded in embedding materials that dogs and cats like to eat, the block composition prepared from the coated drug balls has a dog feeding rate of 91.01% and a cat feeding rate of 82.44% (average of the feeding rates of the 7 test products, see Table 3-1 for specific data, and the data in the table come from 7 pet hospitals).

[0253] The control product of this test was prepared by mixing rice powder, pork floss (15%), sucrose and microcrystalline cellulose as auxiliary materials, and then pressing into tablets by using conventional tabletting technology. Before feeding the block composition, the control product with the same active ingredients as the test product was fed first. The results are shown in Table 3-2.

[0254] Table 3-1 Feeding rate of the block composition of Example 6

[0255]

[0256]

[0257] Table 3-2 Feeding rate of the control product

[0258]

[0259] Six, feeding effect test of the block composition of Example 6

[0260] The three block compositions of Example 6 (Table 4-1 below) were used as test products, and the test results showed that the feeding rate of dogs was 83%-100%, and the feeding rate of cats was 78.26%-100%. The tablets prepared by conventional methods were not liked by dogs and cats, and even if pork floss and other substances were added, the feeding rate was below 50%.

[0261] Table 4-1 Feeding rate of the three block compositions of Example 6

[0262]

[0263] Seven, feeding effect test of the block composition of Example 7

[0264] Test product: the block composition containing vitamins, trace elements and other ingredients described in Example 7;

[0265] Control product: the active ingredients and content are the same as the test product, and the block is prepared by conventional method, i.e. mixing the active ingredients containing vitamins, trace elements and other ingredients described in Example 7 with the embedding material described in Example 7, and then pressing into 18mm x 18mm x 15-16mm blocks by using a briquetting machine;

[0266] The test cats were all pet cats (most of them were American Shorthair) raised at home. The feeding effect test results are shown in Table 5-1 below. The data in Table 5-1 were from cat farms, homes and pet hospitals.

[0267] Table 5-1 Feeding rate of the block composition and control product of Example 7

[0268]

[0269]

[0270] 8. Test on the edibility of the block composition described in Example 8

[0271] The test samples were the three sizes of block compositions described in Example 8;

[0272] The reference standard is praziquantel tablets containing an appetite stimulant, prepared by conventional methods. The preparation process is as follows: praziquantel is dissolved in 95% ethanol, then β-cyclodextrin and sucrose are added, stirred and mixed, dried, and then mixed with the encapsulating material described in Example 1 above. The mixture is then pressed into blocks using a briquetting machine and dried to obtain the reference standard.

[0273] The above three test products and three control products were used to conduct a feeding effect test in six locations (villages) in Xinjiang, with each household having 1-5 dogs. The test method involved placing the test products and control products in two separate food bowls and observing the feeding behavior of the same dog. The results showed that in all six locations, the dogs initially ate the test products, a few then ate the control products, and the majority refused to eat the control products. Specific data are shown in Table 6-1.

[0274] Table 6-1 Test of canine feeding effects on test and control products

[0275]

[0276] IX. Effect Test of the 10mg praziquantel / block composition described in Example 8

[0277] Using the block composition with a praziquantel content of 10 mg described in Example 8 as the test product, the ingestion rate of pet dogs and pet cats was tested. The test results are shown in Table 6-2; the data in Table 6-2 is a summary of the test data from three pet hospitals.

[0278] Thirteen cats were fed the control product described in Experiment 8 above, and none of the cats ate it; 26 pet dogs were fed the control product described in Experiment 8 above, and the consumption rate was 19.6% (not listed in Table 6-2).

[0279] Table 6-2 Efficacy Test of 10mg Praziquantel Block Combination

[0280]

[0281]

[0282] 10. Test on the appetite-inducing effect of the block composition described in Example 11

[0283] Using the three block compositions containing rumen-treated medicated balls described in Example 11 as test products (see Table 7-1 below), active feeding effects on beef cattle and sheep were tested in different locations in Inner Mongolia.

[0284] Table 7-13 test products

[0285]

[0286] The experimental results show that the feeding rate of 21 sheep and 18 beef cattle on the above-mentioned test products (block-shaped compositions) is 95.4% (the average feeding rate of 3 test products) and 88.8% (the average feeding rate of 3 test products), respectively. This experimental result shows that using a tablet press to first prepare the antibacterial drug into a "drug ball" that can pass through the rumen, and then embedding the "drug ball" in food that cattle and sheep love to eat, i.e. using a "block press" to press into a "block-shaped composition" containing a rumen-passing drug ball, can achieve the goal of cattle and sheep taking the initiative to eat, and solve the problem of cattle and sheep feeding medicine. This is especially suitable for confined feeding of cattle and sheep, and the dosage is accurate, and there is no problem of feeding stress reaction (this is very important).

[0287] The various embodiments in the specification are described in a progressive manner, and each embodiment focuses on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to each other.

[0288] The above description of the disclosed embodiments enables a person skilled in the art to implement or use the present application. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present application. Therefore, the present application will not be limited to these embodiments shown herein, but will conform to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A process for the preparation of an animal edible medicated pellet composition, characterized in that: The medicine or bioactive substance is first made into medicine balls, which are then coated or uncoated, and then embedded in the embedding material to make the medicine ball-containing block composition.

2. A process for the preparation of a medicated ball composition edible to animals as claimed in claim 1, wherein: The medicine or bioactive substance is mixed with excipients, and a tablet machine, a pill machine, a drop pill machine or a screw extruder is used to make the medicine balls.

3. A process for the preparation of a medicated ball composition edible to animals as claimed in claim 1, wherein: The block is made using a briquetting machine, and the operating pressure is 500-700 MPa.

4. A process for the preparation of a medicated ball composition edible to animals as claimed in claim 3, wherein: The medicine ball quantitative transfer device is used to fill the medicine balls into the briquetting machine, and the medicine ball quantitative transfer device is sequentially provided with a ball pressing plate, a ball containing plate, a hole sealing plate and a positioning plate from top to bottom. The ball containing plate is provided with a through medicine ball containing hole corresponding to the film hole of the briquetting machine, and the ball containing plate is provided with a plug-in slot on one side facing the hole sealing plate and a medicine adding slot on the other side. The ball pressing plate is provided with a cylinder corresponding to the medicine ball containing hole on the side facing the ball containing plate, and the top of the cylinder is inwardly recessed. The hole sealing plate is a flat plate, and the hole sealing plate is plug-in installed in the plug-in slot. The positioning plate is provided with a positioning column corresponding to the film hole of the briquetting machine on the side away from the hole sealing plate, and the positioning column is provided with a through positioning hole corresponding to the medicine ball containing hole.

5. A process for the preparation of a medicated ball composition edible to animals as claimed in claim 4, wherein: The medicine ball quantitative transfer device is used to fill the medicine balls into the briquetting machine, and the medicine ball quantitative transfer device is sequentially provided with a ball pressing plate, a ball containing plate, a hole sealing plate and a positioning plate from top to bottom. The ball containing plate is provided with a through medicine ball containing hole corresponding to the film hole of the briquetting machine, and the ball containing plate is provided with a plug-in slot on one side facing the hole sealing plate and a medicine adding slot on the other side. The hole sealing plate is a flat plate, and the hole sealing plate is plug-in installed in the plug-in slot.

6. A process for the preparation of a medicated ball composition edible to animals as claimed in claim 5 wherein: The diameter of the medicine ball is 3-8 mm, and the diameter of the medicine ball containing hole is 1-4 mm larger than the diameter of the medicine ball.

7. A process for the preparation of a medicated ball composition edible to animals as claimed in claim 6 wherein: Specifically, the following steps are included: S1, medicine ball preparation: mixing the medicine or bioactive substance with excipients, granulating or not granulating, and using a tablet machine, a pill machine, a drop pill machine or a screw extruder to make medicine balls, wherein the medicine balls are spherical or nearly spherical; S2, filling medicine balls into the quantitative dispenser: when each block composition contains one medicine ball, the hole sealing plate of the quantitative transfer device is inserted into the plug-in slot to seal all the medicine ball containing holes, and then the medicine balls are poured into the medicine adding slot, and the medicine balls are swept into the medicine ball containing holes by the scraper; When each block composition contains multiple medicine balls, multiple dispensing is performed using the quantitative dispenser, the quantitative dispenser loaded with medicine balls is placed on the ball containing plate of the medicine ball quantitative transfer device, the ball containing holes on the quantitative dispenser correspond one-to-one to the medicine ball containing holes on the medicine ball quantitative transfer device, and then the hole sealing plate of the quantitative dispenser is pulled out of the plug-in slot, so that the medicine balls in the ball containing holes fall into the medicine ball containing holes one-to-one, and the dispensing times are set according to the number of medicine balls contained in each block composition; S3, preparation of embedding material for embedding medicine balls: uniformly mixing animal food, food attractant and flavor enhancer, adhesive, preservative, adding wetting agent, thoroughly stirring, soaking, mixing and uniformly mixing to obtain the embedding material; S4, filling the bottom layer embedding material into the briquetting machine mold hole; S5, transferring the medicine balls: the medicine ball quantifying transferer with medicine balls is placed on the die of the briquetting machine, and the positioning columns are dropped into the die holes of the briquetting machine one by one; the hole sealing plate is pulled out, the medicine balls are dropped into the die holes of the briquetting machine, and then the cylinder of the ball pressing plate is used to press the medicine balls in each film hole through the medicine ball containing hole and the positioning hole, so that part of the medicine balls are pressed into the bottom embedding material, and then the medicine ball quantifying transferer is removed; S6, filling the upper embedding material and pressing; S7, drying, coating or not coating the attractant, to obtain the blocky composition.

8. A process for the preparation of a medicated ball composition edible to animals as claimed in claim 7, wherein: The bottom embedding material accounts for 15% to 75% of the total embedding material.

9. The animal edible medicine ball containing blocky composition prepared by the preparation method according to any one of claims 1 to 8.

10. The use of the animal edible medicine ball containing blocky composition according to claim 9 in the preparation of veterinary drugs.

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