WO2022036800A1 - Compound amino acid enteric-coated capsule for dog, and preparation method therefor - Google Patents

Compound amino acid enteric-coated capsule for dog, and preparation method therefor Download PDF

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WO2022036800A1
WO2022036800A1 PCT/CN2020/116380 CN2020116380W WO2022036800A1 WO 2022036800 A1 WO2022036800 A1 WO 2022036800A1 CN 2020116380 W CN2020116380 W CN 2020116380W WO 2022036800 A1 WO2022036800 A1 WO 2022036800A1
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parts
amino acid
dogs
compound amino
enteric
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PCT/CN2020/116380
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French (fr)
Chinese (zh)
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裴有志
陈淑芳
李凤英
王成彬
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河北科星药业有限公司
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
    • A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4172—Imidazole-alkanecarboxylic acids, e.g. histidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/485—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin

Definitions

  • the invention belongs to the technical field of pharmaceutical preparations, and relates to a veterinary drug, in particular to a compound amino acid enteric-coated capsule for dogs and a preparation method thereof.
  • the supplementary fluids used to enhance the physical fitness of dogs are mainly glucose and sodium chloride injections.
  • the injections are mainly used to replenish water and energy, and to adjust the balance of electrolytes in the body, but they cannot improve the nutritional status of dogs and supplement the amino acids required by dogs. .
  • Amino acid is a general term for a class of organic compounds containing amino and carboxyl groups. It is the basic unit of biological functional macromolecular protein and the basic substance that constitutes the protein required for animal nutrition. However, if the amino acid drugs disintegrate in the stomach, the side effects of the dogs are greater, especially for the frail and sick dogs, it is easy to stimulate their stomachs and cause adverse reactions.
  • the absorption of amino acids through the mucosal cells of the small intestine is carried out by the active operating system, which transports neutral, acidic and basic amino acids respectively.
  • the purpose of the present invention is to provide a compound amino acid enteric-coated capsule for dogs, which can avoid irritation to the stomach of dogs while providing nutrition for dogs;
  • Another object of the present invention is to provide the above-mentioned preparation method of compound amino acid enteric-coated capsules for dogs.
  • the present invention is to realize the above-mentioned purpose, and the technical scheme adopted is as follows:
  • a compound amino acid enteric-coated capsule for dogs calculated in 250 parts by weight, the preparation raw materials comprising: 5-7 parts of lysine hydrochloride, 1-4 parts of methionine, 0.5-2 parts of tryptophan, 6-9 parts of amino acid, 2-5 parts of isoleucine, 1-4 parts of valine, 4-7 parts of phenylalanine, 3-6 parts of histidine hydrochloride, 4-7 parts of arginine hydrochloride , 2 to 5 parts of threonine, 2 to 5 parts of lubricant, and the balance of diluent;
  • Described lubricant is any one or two in magnesium stearate, talc mixed in any ratio;
  • the diluent is one or two of starch and microcrystalline cellulose mixed in any ratio.
  • the raw materials for its preparation include: 6.66 parts of lysine hydrochloride, 2.12 parts of methionine, 0.78 parts of tryptophan, 7.58 parts of leucine, 3.40 parts of isoleucine, valeric acid 2.72 parts of amino acid, 5.66 parts of phenylalanine, 4.92 parts of histidine hydrochloride, 5.78 parts of arginine hydrochloride, 3.94 parts of threonine, 4.00 parts of lubricant and 202.44 parts of thinner.
  • the invention also discloses a preparation method of the above-mentioned compound amino acid enteric-coated capsule for dogs, comprising the following steps performed in sequence:
  • step S1 when each raw material is sieved separately, lysine hydrochloride, methionine, tryptophan, leucine, isoleucine, valine, phenylalanine, hydrochloric acid Histidine, arginine hydrochloride and threonine were passed through a 100-mesh sieve respectively, and the diluent and lubricant were passed through an 80-mesh sieve respectively.
  • step S2 is performed in the following order of steps:
  • the solvent of the hypromellose solution with a mass concentration of 2% is an ethanol solution with a mass concentration of 50%.
  • the dry particles B are sized with a 20-mesh sieve.
  • Compound amino acid enteric-coated capsules for dogs provided by the present invention disintegrates and absorbs in the dog intestine, reduces the adverse reactions caused by the stimulation of the stomach due to the disintegration and absorption of the medicine in the stomach, and reduces the appetite of the medicine for the dog. It contains 10 kinds of amino acids, which supplement the demand for amino acids in dogs;
  • the compound amino acid enteric-coated capsules for dogs provided by the present invention reduce the adverse reactions caused by stimulating the stomach, reduce the adverse effects of drugs on the dog's appetite, and supplement the demand for amino acids in dogs.
  • the stability and good appearance of the active ingredients of the medicine are ensured, the shelf life of the medicine is prolonged, and the preparation method is simple to operate.
  • the invention belongs to the technical field of veterinary drugs, and is suitable for preparing compound amino acid enteric-coated capsules for dogs.
  • Embodiment 1 ⁇ 6 a kind of compound amino acid enteric-coated capsule for dogs
  • Embodiments 1 to 6 respectively provide a compound amino acid enteric-coated capsule for dogs, and the raw materials for making its active ingredients are shown in Table 1.
  • the lubricant is one or both of magnesium stearate and talc and can be mixed in any ratio
  • the diluent is one or both of starch and microcrystalline cellulose can be mixed in any ratio.
  • Examples 1 to 6 are only representative examples.
  • Embodiment 7 A kind of preparation method of compound amino acid enteric-coated capsules for dogs
  • This step is performed in the following order,
  • S12 pass lysine hydrochloride, methionine, tryptophan, leucine, isoleucine, valine, phenylalanine, histidine hydrochloride, arginine hydrochloride and threonine respectively 100 mesh sieve, pass the diluent and lubricant through 80 mesh sieve respectively;
  • This step is performed in the following order,
  • the solvent of the hypromellose solution is an ethanol solution with a mass concentration of 50%;
  • the dry granules B are sieved with a 20-mesh sieve, added with lubricant, mixed evenly, filled into enteric-coated capsule shells, and made into 1,000,000 granules to obtain compound amino acid enteric-coated capsules for dogs.
  • the enteric-coated capsule shell used in this example is a commercially available product.
  • test results of compound amino acid enteric-coated capsules for dogs prepared according to the formulas of Examples 1 to 6 all meet the requirements of product quality standards, and the amino acid content can meet the nutritional needs of dogs for amino acids.
  • the test results of disintegration time limit show that the enteric-coated capsules prepared according to the preparation method of Example 7 are not disintegrated and absorbed in the stomach, but disintegrated and absorbed in the intestines using the formulations of Examples 1-6.
  • the compound amino acid enteric-coated capsule for dogs of the invention is disintegrated and absorbed in the dog's intestine, thereby reducing the adverse reaction caused by stimulation to the dog's stomach, and reducing the adverse effect of the medicine on the dog's appetite.
  • a total of 180 Beagle dogs clinically diagnosed with protein deficiency were selected and randomly divided into 12 groups, namely control group 1-6 and experimental group 1-6.
  • the diseased dogs showed weight loss, rough and dull coat, weight loss, appetite Depressed and lethargic.
  • the formula of compound amino acid stomach-dissolving capsules for dogs is similar to that of Examples 1-6 one-to-one, and the preparation steps are similar to those of Example 7, and the difference is only in that :
  • the capsule shell used is replaced by the enteric-coated capsule shell to the stomach-coated capsule shell), 5 capsules/time/day, used for 7 days; test groups 1 to 6 sick dogs are respectively orally administered according to the method of Example 7, using Example 1
  • the body weight, food intake, adverse reactions, coat condition and mental state of the sick dogs were counted and recorded.
  • the specific usage, dosage and test results are summarized in Table 4 below.
  • the stomach-dissolving capsule shell in this embodiment is a commercially available product.

Abstract

The present application relates to the technical field of veterinary drugs, and specifically discloses a compound amino acid enteric-coated capsule for a dog. Based on 250 parts by weight, the raw materials for preparing the capsule comprise: 5-7 parts of lysine hydrochloride, 1-4 parts of methionine, 0.5-2 parts of tryptophan, 6-9 parts of leucine, 2-5 parts of isoleucine, 1-4 parts of valine, 4-7 parts of phenylalanine, 3-6 parts of histidine hydrochloride, 4-7 parts of arginine hydrochloride, 2-5 parts of threonine, 2-5 parts of a lubricant, and the remainder being a diluent. The compound amino acid enteric-coated capsule for a dog reduces adverse reactions caused by irritation to the stomach, reduces adverse effects of the drug on the appetite of dogs, supplements amino acids needed by the dogs' bodies, ensures the stability of active ingredients and good appearance of the drug, and prolongs the shelf life of the drug; moreover, the preparation method for the capsule is simple to operate, and is suitable for preparing the compound amino acid enteric-coated capsule for a dog.

Description

一种犬用复方氨基酸肠溶胶囊及其制备方法A kind of compound amino acid enteric-coated capsule for dogs and preparation method thereof 技术领域technical field
本发明属于医药制剂技术领域，涉及一种兽药，具体地说是一种犬用复方氨基酸肠溶胶囊及其制备方法。The invention belongs to the technical field of pharmaceutical preparations, and relates to a veterinary drug, in particular to a compound amino acid enteric-coated capsule for dogs and a preparation method thereof.
背景技术Background technique
现在越来越多的家庭选择驯养犬类宠物，但是有的犬体弱多病，一般情况下，常表现出食欲下降、采食量减少、身体虚弱等症状，出现上述症状后，犬体内的营养物质会随着时间的延长而大量流失，如果上述症状得不到及时改善，就会导致犬生长缓慢甚至死亡。Nowadays, more and more families choose to domesticate canine pets, but some dogs are weak and sickly. Under normal circumstances, they often show symptoms such as decreased appetite, reduced feed intake, and physical weakness. With the extension of time and a large amount of loss, if the above symptoms are not improved in time, it will lead to slow growth or even death of the dog.
目前用于增强犬体能的补充液主要为葡萄糖、氯化钠注射液，注射液主要起补充水分和能量，以及调节机体电解质的平衡作用，但无法改善犬体营养状况和补充犬体所需氨基酸。At present, the supplementary fluids used to enhance the physical fitness of dogs are mainly glucose and sodium chloride injections. The injections are mainly used to replenish water and energy, and to adjust the balance of electrolytes in the body, but they cannot improve the nutritional status of dogs and supplement the amino acids required by dogs. .
氨基酸是含有氨基和羧基的一类有机化合物的通称，是生物功能大分子蛋白质的基本组成单位，也是构成动物营养所需蛋白质的基本物质。而如果氨基酸类药物在胃内崩解，对犬的副作用较大，尤其对体弱多病的犬，容易对其胃部产生刺激，进而引发不良反应。Amino acid is a general term for a class of organic compounds containing amino and carboxyl groups. It is the basic unit of biological functional macromolecular protein and the basic substance that constitutes the protein required for animal nutrition. However, if the amino acid drugs disintegrate in the stomach, the side effects of the dogs are greater, especially for the frail and sick dogs, it is easy to stimulate their stomachs and cause adverse reactions.
氨基酸的吸收通过小肠黏膜细胞，是由主动运转***进行，分别转运中性、酸性和碱性氨基酸。The absorption of amino acids through the mucosal cells of the small intestine is carried out by the active operating system, which transports neutral, acidic and basic amino acids respectively.
因此，如果能够发明一种在胃内不崩解的氨基酸营养药物，减少对犬胃部刺激，将会极大地改变上述现状。Therefore, if we can invent an amino acid nutritional medicine that does not disintegrate in the stomach and reduce the irritation to the dog's stomach, it will greatly change the above status quo.
发明内容SUMMARY OF THE INVENTION
本发明的目的，是要提供一种犬用复方氨基酸肠溶胶囊，其在为犬提供营养的同时，能够避免对犬的胃部产生刺激；The purpose of the present invention is to provide a compound amino acid enteric-coated capsule for dogs, which can avoid irritation to the stomach of dogs while providing nutrition for dogs;
本发明的另外一个目的，是要提供上述一种犬用复方氨基酸肠溶胶囊的制备方法。Another object of the present invention is to provide the above-mentioned preparation method of compound amino acid enteric-coated capsules for dogs.
本发明为实现上述目的，所采用的技术方案如下：The present invention is to realize the above-mentioned purpose, and the technical scheme adopted is as follows:
一种犬用复方氨基酸肠溶胶囊，以250份重量份数计，其制备原料包括：盐酸赖氨酸5～7份、甲硫氨酸1～4份、色氨酸0.5～2份、亮氨酸6～9份、异亮氨酸2～5份、缬氨酸1～4份、苯丙氨酸4～7份、盐酸组氨酸3～6份、盐酸精氨酸 4～7份、苏氨酸2～5份、润滑剂2～5份、余量为稀释剂；A compound amino acid enteric-coated capsule for dogs, calculated in 250 parts by weight, the preparation raw materials comprising: 5-7 parts of lysine hydrochloride, 1-4 parts of methionine, 0.5-2 parts of tryptophan, 6-9 parts of amino acid, 2-5 parts of isoleucine, 1-4 parts of valine, 4-7 parts of phenylalanine, 3-6 parts of histidine hydrochloride, 4-7 parts of arginine hydrochloride , 2 to 5 parts of threonine, 2 to 5 parts of lubricant, and the balance of diluent;
所述润滑剂是硬脂酸镁、滑石粉中的任意一种或两种以任意比混合；Described lubricant is any one or two in magnesium stearate, talc mixed in any ratio;
所述稀释剂是淀粉、微晶纤维素中的一种或两种以任意比混合。The diluent is one or two of starch and microcrystalline cellulose mixed in any ratio.
作为限定，以250份重量份数计，其制备原料包括：盐酸赖氨酸6.66份、甲硫氨酸2.12份、色氨酸0.78份、亮氨酸7.58份、异亮氨酸3.40份、缬氨酸2.72份、苯丙氨酸5.66份、盐酸组氨酸4.92份、盐酸精氨酸5.78份、苏氨酸3.94份、润滑剂4.00份和稀释剂202.44份。As a limitation, based on 250 parts by weight, the raw materials for its preparation include: 6.66 parts of lysine hydrochloride, 2.12 parts of methionine, 0.78 parts of tryptophan, 7.58 parts of leucine, 3.40 parts of isoleucine, valeric acid 2.72 parts of amino acid, 5.66 parts of phenylalanine, 4.92 parts of histidine hydrochloride, 5.78 parts of arginine hydrochloride, 3.94 parts of threonine, 4.00 parts of lubricant and 202.44 parts of thinner.
本发明还公开了上述一种犬用复方氨基酸肠溶胶囊的一种制备方法，包括依次进行的以下步骤：The invention also discloses a preparation method of the above-mentioned compound amino acid enteric-coated capsule for dogs, comprising the following steps performed in sequence:
S1、称取各原料，然后将各原料分别过筛，再将盐酸赖氨酸、甲硫氨酸、色氨酸、亮氨酸、异亮氨酸、缬氨酸、苯丙氨酸、盐酸组氨酸、盐酸精氨酸、苏氨酸和稀释剂混合均匀，得物料A；S1, weigh each raw material, then sieve each raw material respectively, then lysine hydrochloride, methionine, tryptophan, leucine, isoleucine, valine, phenylalanine, hydrochloric acid Histidine, arginine hydrochloride, threonine and diluent are evenly mixed to obtain material A;
S2、将物料A通过湿法制粒，然后烘干，制得干颗粒B；S2, wet granulation of material A, and then drying to obtain dry granules B;
S3、将干颗粒B整粒，然后加入润滑剂混合均匀，灌装入肠溶胶囊壳中，即得所述一种犬用复方氨基酸肠溶胶囊。S3, granulate the dry granule B, then add a lubricant to mix evenly, and fill it into an enteric-coated capsule shell to obtain the compound amino acid enteric-coated capsule for dogs.
作为限定，所述步骤S1中将各原料分别过筛时，将盐酸赖氨酸、甲硫氨酸、色氨酸、亮氨酸、异亮氨酸、缬氨酸、苯丙氨酸、盐酸组氨酸、盐酸精氨酸、苏氨酸分别过100目筛，将稀释剂、润滑剂分别过80目筛。As a limitation, in the step S1, when each raw material is sieved separately, lysine hydrochloride, methionine, tryptophan, leucine, isoleucine, valine, phenylalanine, hydrochloric acid Histidine, arginine hydrochloride and threonine were passed through a 100-mesh sieve respectively, and the diluent and lubricant were passed through an 80-mesh sieve respectively.
作为第二种限定，所述步骤S2按照以下步骤顺序进行：As a second limitation, the step S2 is performed in the following order of steps:
S21、将物料A用质量浓度为2％的羟丙甲纤维素溶液湿法制粒，过24目筛制得湿颗粒A1；S21, wet granulation of material A with a 2% hypromellose solution, sieving through a 24-mesh sieve to obtain wet granules A1;
S22、将湿颗粒A1在115℃条件下烘干，制得干颗粒B；S22, drying the wet particles A1 at 115°C to obtain dry particles B;
所述质量浓度为2％的羟丙甲纤维素溶液的溶剂是质量浓度为50％的乙醇溶液。The solvent of the hypromellose solution with a mass concentration of 2% is an ethanol solution with a mass concentration of 50%.
作为第三种限定，所述步骤S3中，将干颗粒B以20目筛整粒。As a third limitation, in the step S3, the dry particles B are sized with a 20-mesh sieve.
本发明由于采用了上述的技术方案，其与现有技术相比，所取得的技术进步在于：Because the present invention adopts the above-mentioned technical scheme, compared with the prior art, the technical progress achieved is:
(1)本发明提供的犬用复方氨基酸肠溶胶囊，在犬肠内崩解吸收，减少因药物在胃部崩解吸收对胃部产生刺激而引发的不良反应，降低了药物对犬食欲产生的不良影响，而且含有的10种氨基酸，补充了犬体内对氨基酸的需求；(1) Compound amino acid enteric-coated capsules for dogs provided by the present invention disintegrates and absorbs in the dog intestine, reduces the adverse reactions caused by the stimulation of the stomach due to the disintegration and absorption of the medicine in the stomach, and reduces the appetite of the medicine for the dog. It contains 10 kinds of amino acids, which supplement the demand for amino acids in dogs;
(2)本发明提供的犬用复方氨基酸肠溶胶囊，产品稳定性好；(2) Compound amino acid enteric-coated capsules for dogs provided by the present invention have good product stability;
(3)本发明提供的犬用复方氨基酸肠溶胶囊的制备方法，操作简单，适用于大规模生产。(3) The preparation method of compound amino acid enteric-coated capsules for dogs provided by the present invention is simple to operate and suitable for large-scale production.
综上所述，本发明提供的犬用复方氨基酸肠溶胶囊，减少了对胃部产生刺激而引发的不良反应，降低了药物对犬食欲产生的不良影响，补充了犬体内对氨基酸的需求，保证了药物有效成分的稳定和良好的外观，延长了药物的保质期，而且其制备方法操作简单。To sum up, the compound amino acid enteric-coated capsules for dogs provided by the present invention reduce the adverse reactions caused by stimulating the stomach, reduce the adverse effects of drugs on the dog's appetite, and supplement the demand for amino acids in dogs. The stability and good appearance of the active ingredients of the medicine are ensured, the shelf life of the medicine is prolonged, and the preparation method is simple to operate.
本发明属于兽药技术领域，适用于制备犬用复方氨基酸肠溶胶囊。The invention belongs to the technical field of veterinary drugs, and is suitable for preparing compound amino acid enteric-coated capsules for dogs.
具体实施方式detailed description
以下对本发明的优选实施例进行说明。应当理解，此处所描述的优选实施例仅用于说明和解释本发明，并不用于限定本发明。Preferred embodiments of the present invention will be described below. It should be understood that the preferred embodiments described herein are only used to illustrate and explain the present invention, but not to limit the present invention.
实施例1～6一种犬用复方氨基酸肠溶胶囊Embodiment 1～6 a kind of compound amino acid enteric-coated capsule for dogs
实施例1～6分别提供了一种犬用复方氨基酸肠溶胶囊，制成其有效成分的原料如表1所示。Embodiments 1 to 6 respectively provide a compound amino acid enteric-coated capsule for dogs, and the raw materials for making its active ingredients are shown in Table 1.
表1实施例1～6犬用复方氨基酸肠溶胶囊的原料The raw materials of compound amino acid enteric-coated capsules for dogs in Table 1 Examples 1-6
Figure PCTCN2020116380-appb-000001
Figure PCTCN2020116380-appb-000001
实际操作中，润滑剂为硬脂酸镁、滑石粉中的一种或两种以任意比混合皆可，稀释剂为淀粉、微晶纤维素中的一种或两种以任意比混合皆可，实施例1～6只是给出了具有代表性的例子。In actual operation, the lubricant is one or both of magnesium stearate and talc and can be mixed in any ratio, and the diluent is one or both of starch and microcrystalline cellulose can be mixed in any ratio. , Examples 1 to 6 are only representative examples.
实施例7一种犬用复方氨基酸肠溶胶囊的制备方法Embodiment 7 A kind of preparation method of compound amino acid enteric-coated capsules for dogs
本实施例用于制备实施例1～6，制备方法按照以下步骤顺序进行：This example is used to prepare Examples 1 to 6, and the preparation method is carried out in the following order of steps:
S1、混料S1. Mixing
本步骤按照以下步骤顺序进行，This step is performed in the following order,
S11、按照实施例1～6中所示的各原料重量分别称取各原料；S11, weigh each raw material according to the weight of each raw material shown in Examples 1-6;
S12、将盐酸赖氨酸、甲硫氨酸、色氨酸、亮氨酸、异亮氨酸、缬氨酸、苯丙氨 酸、盐酸组氨酸、盐酸精氨酸、苏氨酸分别过100目筛，将稀释剂、润滑剂分别过80目筛；S12, pass lysine hydrochloride, methionine, tryptophan, leucine, isoleucine, valine, phenylalanine, histidine hydrochloride, arginine hydrochloride and threonine respectively 100 mesh sieve, pass the diluent and lubricant through 80 mesh sieve respectively;
S13、将盐酸赖氨酸、甲硫氨酸、色氨酸、亮氨酸、异亮氨酸、缬氨酸、苯丙氨酸、盐酸组氨酸、盐酸精氨酸、苏氨酸和稀释剂混合均匀，得物料A；S13, dilute lysine hydrochloride, methionine, tryptophan, leucine, isoleucine, valine, phenylalanine, histidine hydrochloride, arginine hydrochloride, threonine and dilute The agent is mixed evenly to obtain material A;
S2、制粒S2, granulation
本步骤按照以下步骤顺序进行，This step is performed in the following order,
S21、将物料A用质量浓度为2％的羟丙甲纤维素溶液湿法制粒，过24目筛制得湿颗粒A1；S21, wet granulation of material A with a 2% hypromellose solution, sieving through a 24-mesh sieve to obtain wet granules A1;
其中，羟丙甲纤维素溶液的溶剂是质量浓度为50％的乙醇溶液；Wherein, the solvent of the hypromellose solution is an ethanol solution with a mass concentration of 50%;
S22、将湿颗粒A1在115℃条件下烘干，制得干颗粒B；S22, drying the wet particles A1 at 115°C to obtain dry particles B;
S3、灌装S3. Filling
将干颗粒B以20目筛整粒，加入润滑剂，混合均匀，灌装入肠溶胶囊壳中，制成1000000粒，即得犬用复方氨基酸肠溶胶囊。The dry granules B are sieved with a 20-mesh sieve, added with lubricant, mixed evenly, filled into enteric-coated capsule shells, and made into 1,000,000 granules to obtain compound amino acid enteric-coated capsules for dogs.
本实施例采用的肠溶胶囊壳为市售产品。The enteric-coated capsule shell used in this example is a commercially available product.
实施例8犬用复方氨基酸肠溶胶囊的质量检测Example 8 Quality detection of compound amino acid enteric-coated capsules for dogs
参照产品质量标准规定的方法对采用实施例1～6的配方，按照实施例7提供的制备方法制成的犬用复方氨基酸肠溶胶囊的质量进行检验，检测结果如表2所示。With reference to the method specified in the product quality standard, the quality of compound amino acid enteric-coated capsules for dogs prepared by the formulations of Examples 1 to 6 and the preparation method provided in Example 7 was tested. The test results are shown in Table 2.
表2实施例1～6的犬用复方氨基酸肠溶胶囊质量检测结果The quality test result of compound amino acid enteric-coated capsules for dogs of table 2 embodiment 1～6
Figure PCTCN2020116380-appb-000002
Figure PCTCN2020116380-appb-000002
由上表可知，按照实施例1～6的配方制备的犬用复方氨基酸肠溶胶囊各项检测结果均符合产品质量标准规定，氨基酸含量能够满足犬对氨基酸的营养需求。崩解时限检测结果表明，采用实施例1～6的配方，按照实施例7的制备方法制得的肠溶胶囊均不在胃部崩解吸收，而在肠内崩解吸收，由此可见，本发明的犬用复方氨基酸肠溶胶囊，在犬肠内崩解吸收，减少了对犬胃部产生刺激而引发的不良反应，降低了药物对犬食欲产生的不良影响。As can be seen from the above table, the test results of compound amino acid enteric-coated capsules for dogs prepared according to the formulas of Examples 1 to 6 all meet the requirements of product quality standards, and the amino acid content can meet the nutritional needs of dogs for amino acids. The test results of disintegration time limit show that the enteric-coated capsules prepared according to the preparation method of Example 7 are not disintegrated and absorbed in the stomach, but disintegrated and absorbed in the intestines using the formulations of Examples 1-6. The compound amino acid enteric-coated capsule for dogs of the invention is disintegrated and absorbed in the dog's intestine, thereby reducing the adverse reaction caused by stimulation to the dog's stomach, and reducing the adverse effect of the medicine on the dog's appetite.
实施例9犬用复方氨基酸肠溶胶囊的稳定性测试Example 9 Stability test of compound amino acid enteric-coated capsules for dogs
对采用实施例1～6的配方，按照实施例7提供的制备方法制成的犬用复方氨基酸肠溶胶囊进行稳定性考察，具体实施方案如下：The compound amino acid enteric-coated capsules for dogs prepared according to the preparation method provided in Example 7 using the formulations of Examples 1 to 6 were investigated for stability. The specific embodiments are as follows:
将上述犬用复方氨基酸肠溶胶囊，在温度40℃±2℃、相对湿度75％±5％的条件下放置6个月，按产品质量标准进行检验，检验结果如下表3所示。The above-mentioned compound amino acid enteric-coated capsules for dogs were placed for 6 months under the conditions of a temperature of 40 ° C ± 2 ° C and a relative humidity of 75% ± 5%, and tested according to the product quality standards. The test results are shown in Table 3 below.
表3实施例1～6的犬用复方氨基酸肠溶胶囊稳定性测试结果The stability test result of compound amino acid enteric-coated capsules for dogs of table 3 embodiment 1～6
Figure PCTCN2020116380-appb-000003
Figure PCTCN2020116380-appb-000003
由上表可知，经6个月的加速试验，采用实施例1～6提供的配方，按照实施例7提供的制备方法制备的犬用复方氨基酸肠溶胶囊各项检测数据无显著变化，表明上述犬用复方氨基酸肠溶胶囊产品稳定性良好。As can be seen from the above table, after 6 months of accelerated testing, using the formulas provided in Examples 1 to 6, the compound amino acid enteric-coated capsules for dogs prepared according to the preparation method provided in Example 7 have no significant changes in the detection data, indicating that the above Compound amino acid enteric-coated capsules for dogs have good stability.
实施例9犬用复方氨基酸肠溶胶囊有效性试验Example 9 Effectiveness test of compound amino acid enteric-coated capsules for dogs
选取经临床诊断为蛋白质缺乏症的比格犬180只，随机分成12组，分别为对照组1～6和试验组1～6，病犬表现为消瘦、被毛粗硬无光泽、体重减轻、食欲不振及精神萎靡。A total of 180 Beagle dogs clinically diagnosed with protein deficiency were selected and randomly divided into 12 groups, namely control group 1-6 and experimental group 1-6. The diseased dogs showed weight loss, rough and dull coat, weight loss, appetite Depressed and lethargic.
其中对照组1～6病犬口服犬用复方氨基酸胃溶胶囊(犬用复方氨基酸胃溶胶囊的配方分别与实施例1～6一一对应相似、制备步骤与实施例7相似，不同之处仅在于：所用胶囊壳由肠溶胶囊壳更换为胃溶胶囊壳)，5粒/次/日，连用7日；试验组1～6病犬分别一一对应口服按照实施例7的方法，采用实施例1～6的配方制备的犬用复方氨基酸肠溶胶囊，5粒/次/日，连用7日。统计并记录病犬的体重、进食量、不良反应、被毛状况及精神状态，具体用法用量及试验结果汇总如下表4所示。Wherein the control group 1-6 sick dogs orally take compound amino acid stomach-dissolving capsules for dogs (the formula of compound amino acid stomach-dissolving capsules for dogs is similar to that of Examples 1-6 one-to-one, and the preparation steps are similar to those of Example 7, and the difference is only in that : The capsule shell used is replaced by the enteric-coated capsule shell to the stomach-coated capsule shell), 5 capsules/time/day, used for 7 days; test groups 1 to 6 sick dogs are respectively orally administered according to the method of Example 7, using Example 1 Compound amino acid enteric-coated capsules for dogs prepared with the formula of ~6, 5 capsules/time/day, for 7 consecutive days. The body weight, food intake, adverse reactions, coat condition and mental state of the sick dogs were counted and recorded. The specific usage, dosage and test results are summarized in Table 4 below.
表4犬用复方氨基酸肠溶胶囊有效性试验Table 4 Effectiveness test of compound amino acid enteric-coated capsules for dogs
Figure PCTCN2020116380-appb-000004
Figure PCTCN2020116380-appb-000004
本实施例中的胃溶胶囊壳为市售产品。The stomach-dissolving capsule shell in this embodiment is a commercially available product.
由上表可知，经过7日的治疗观察，对照组1～6病犬进食量均有增加，体重均有增长，被毛状况及精神状态未见改善，均有犬出现呕吐反应，而试验组1～8的病犬进食量均有增加，体重均有增长，进食量增加和体重增长幅度均优 于对照组，被毛及精神状态也均有改善，未见呕吐反应。试验结果表明，本发明提供的一种犬用复方氨基酸肠溶胶囊能够补充犬体对氨基酸的需求，降低药物对患犬食欲产生的不良影响。It can be seen from the above table that after 7 days of treatment and observation, the food intake of the control group 1 to 6 patients increased, the body weight increased, the coat condition and mental state did not improve, and all dogs had vomiting reaction, while the experimental group 1. The sick dogs of ~8 all increased their food intake and body weight. The increase in food intake and body weight were better than those of the control group. The coat and mental state were also improved, and no vomiting was found. The test results show that the compound amino acid enteric-coated capsule for dogs provided by the present invention can supplement the requirement of the dog's body for amino acids and reduce the adverse effect of the drug on the appetite of the dog.

Claims (7)

  1. 一种犬用复方氨基酸肠溶胶囊，其特征在于，以250份重量份数计，其制备原料包括：盐酸赖氨酸5～7份、甲硫氨酸1～4份、色氨酸0.5～2份、亮氨酸6～9份、异亮氨酸2～5份、缬氨酸1～4份、苯丙氨酸4～7份、盐酸组氨酸3～6份、盐酸精氨酸4～7份、苏氨酸2～5份、润滑剂2～5份、余量为稀释剂；A compound amino acid enteric-coated capsule for dogs, characterized in that, based on 250 parts by weight, the preparation raw materials include: 5-7 parts of lysine hydrochloride, 1-4 parts of methionine, and 0.5-4 parts of tryptophan. 2 parts, 6-9 parts leucine, 2-5 parts isoleucine, 1-4 parts valine, 4-7 parts phenylalanine, 3-6 parts histidine hydrochloride, arginine hydrochloride 4 to 7 parts, 2 to 5 parts of threonine, 2 to 5 parts of lubricant, and the balance is diluent;
    所述润滑剂是硬脂酸镁、滑石粉中的任意一种或两种以任意比混合；Described lubricant is any one or two in magnesium stearate, talc mixed in any ratio;
    所述稀释剂是淀粉、微晶纤维素中的一种或两种以任意比混合。The diluent is one or two of starch and microcrystalline cellulose mixed in any ratio.
  2. 根据权利要求1所述的一种犬用复方氨基酸肠溶胶囊，其特征在于，以250份重量份数计，其制备原料包括：盐酸赖氨酸6.66份、甲硫氨酸2.12份、色氨酸0.78份、亮氨酸7.58份、异亮氨酸3.40份、缬氨酸2.72份、苯丙氨酸5.66份、盐酸组氨酸4.92份、盐酸精氨酸5.78份、苏氨酸3.94份、润滑剂4.00份和稀释剂202.44份。A kind of compound amino acid enteric-coated capsule for dogs according to claim 1, is characterized in that, in 250 parts by weight, its preparation raw material comprises: 6.66 parts of lysine hydrochloride, 2.12 parts of methionine, tryptophan 0.78 parts of acid, 7.58 parts of leucine, 3.40 parts of isoleucine, 2.72 parts of valine, 5.66 parts of phenylalanine, 4.92 parts of histidine hydrochloride, 5.78 parts of arginine hydrochloride, 3.94 parts of threonine, 4.00 parts of lubricant and 202.44 parts of thinner.
  3. 根据权利要求1或2所述的一种犬用复方氨基酸肠溶胶囊一种制备方法，其特征在于，包括依次进行的以下步骤：A kind of preparation method of compound amino acid enteric-coated capsules for dogs according to claim 1 and 2, is characterized in that, comprises the following steps that carry out successively:
    S1、称取各原料，然后将各原料分别过筛，再将盐酸赖氨酸、甲硫氨酸、色氨酸、亮氨酸、异亮氨酸、缬氨酸、苯丙氨酸、盐酸组氨酸、盐酸精氨酸、苏氨酸和稀释剂混合均匀，得物料A；S1, weigh each raw material, then sieve each raw material respectively, then lysine hydrochloride, methionine, tryptophan, leucine, isoleucine, valine, phenylalanine, hydrochloric acid Histidine, arginine hydrochloride, threonine and diluent are evenly mixed to obtain material A;
    S2、将物料A通过湿法制粒，然后烘干，制得干颗粒B；S2, wet granulation of material A, and then drying to obtain dry granules B;
    S3、将干颗粒B整粒，然后加入润滑剂混合均匀，灌装入肠溶胶囊壳中，即得所述一种犬用复方氨基酸肠溶胶囊。S3, granulate the dry granule B, then add a lubricant to mix evenly, and fill it into an enteric-coated capsule shell to obtain the compound amino acid enteric-coated capsule for dogs.
  4. 根据权利要求3所述的一种犬用复方氨基酸肠溶胶囊的制备方法，其特征在于，所述步骤S1中将各原料分别过筛时，将盐酸赖氨酸、甲硫氨酸、色氨酸、亮氨酸、异亮氨酸、缬氨酸、苯丙氨酸、盐酸组氨酸、盐酸精氨酸、苏氨酸分别过100目筛，将稀释剂、润滑剂分别过80目筛。A kind of preparation method of compound amino acid enteric-coated capsules for dogs according to claim 3, is characterized in that, when each raw material is sieved respectively in described step S1, lysine hydrochloride, methionine, tryptophan Acid, leucine, isoleucine, valine, phenylalanine, histidine hydrochloride, arginine hydrochloride, and threonine were passed through a 100-mesh sieve respectively, and the diluent and lubricant were passed through an 80-mesh sieve respectively .
  5. 根据权利要求3或4所述的一种犬用复方氨基酸肠溶胶囊的制备方法，其特征在于，所述步骤S2按照以下步骤顺序进行：A kind of preparation method of compound amino acid enteric-coated capsules for dogs according to claim 3 or 4, is characterized in that, described step S2 is carried out according to the following step sequence:
    S21、将物料A用质量浓度为2％的羟丙甲纤维素溶液湿法制粒，过24目筛制得湿颗粒A1；S21, wet granulation of material A with a 2% hypromellose solution, sieving through a 24-mesh sieve to obtain wet granules A1;
    S22、将湿颗粒A1在115℃条件下烘干，制得干颗粒B；S22, drying the wet particles A1 at 115°C to obtain dry particles B;
    所述质量浓度为2％的羟丙甲纤维素溶液的溶剂是质量浓度为50％的乙醇溶液。The solvent of the hypromellose solution with a mass concentration of 2% is an ethanol solution with a mass concentration of 50%.
  6. 根据权利要求3或4所述的一种犬用复方氨基酸肠溶胶囊的制备方法，其特征在于，所述步骤S3中，将干颗粒B以20目筛整粒。The method for preparing a compound amino acid enteric-coated capsule for dogs according to claim 3 or 4, wherein in the step S3, the dry particles B are sized with a 20-mesh sieve.
  7. 根据权利要求5所述的一种犬用复方氨基酸肠溶胶囊的制备方法，其特征在于，所述步骤S3中，将干颗粒B以20目筛整粒。The method for preparing a compound amino acid enteric-coated capsule for dogs according to claim 5, wherein in the step S3, the dry particles B are sized with a 20-mesh sieve.
PCT/CN2020/116380 2020-08-18 2020-09-21 Compound amino acid enteric-coated capsule for dog, and preparation method therefor WO2022036800A1 (en)

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