CN109364042B - Traditional Chinese medicine targeted tilmicosin micro-pill and preparation method thereof - Google Patents

Traditional Chinese medicine targeted tilmicosin micro-pill and preparation method thereof Download PDF

Info

Publication number
CN109364042B
CN109364042B CN201811418549.7A CN201811418549A CN109364042B CN 109364042 B CN109364042 B CN 109364042B CN 201811418549 A CN201811418549 A CN 201811418549A CN 109364042 B CN109364042 B CN 109364042B
Authority
CN
China
Prior art keywords
tilmicosin
coating
parts
pellet
traditional chinese
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201811418549.7A
Other languages
Chinese (zh)
Other versions
CN109364042A (en
Inventor
赵云英
付宝明
常靖
叶超
王玉
张苗
苏杰红
张志峰
满树建
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
HEBEI DEPOND ANIMAL HEALTH TECHNOLOGY CO LTD
Original Assignee
HEBEI DEPOND ANIMAL HEALTH TECHNOLOGY CO LTD
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by HEBEI DEPOND ANIMAL HEALTH TECHNOLOGY CO LTD filed Critical HEBEI DEPOND ANIMAL HEALTH TECHNOLOGY CO LTD
Priority to CN201811418549.7A priority Critical patent/CN109364042B/en
Publication of CN109364042A publication Critical patent/CN109364042A/en
Application granted granted Critical
Publication of CN109364042B publication Critical patent/CN109364042B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/34Campanulaceae (Bellflower family)
    • A61K36/346Platycodon
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005Wall or coating material
    • A61K9/5021Organic macromolecular compounds
    • A61K9/5036Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A61K9/5042Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Microbiology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Botany (AREA)
  • Mycology (AREA)
  • Medical Informatics (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Virology (AREA)
  • Inorganic Chemistry (AREA)
  • Pulmonology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to a traditional Chinese medicine targeted tilmicosin pellet and a preparation method thereof, wherein the traditional Chinese medicine targeted tilmicosin pellet comprises the following raw materials in parts by weight: 20 parts of tilmicosin; 5-10 parts of platycodon grandiflorum superfine powder; 1-8 parts of pubescent holly root superfine powder; disintegrating agent: 10-35 parts; adhesive: 5-10 parts; filling agent: 1-15 parts. The preparation method comprises the following steps: 1. respectively crushing platycodon grandiflorum and pubescent holly root, and sieving with a 350-mesh sieve to obtain superfine platycodon grandiflorum powder and superfine pubescent holly root powder; 2. dissolving rhizoma bletilla polysaccharide gum with water, and stirring to obtain rhizoma bletilla polysaccharide gum water solution; 3. stirring tilmicosin, radix Platycodi ultra-fine powder, radix Ilicis Pubescentis ultra-fine powder, disintegrating agent and filler for 10min, adding rhizoma Bletillae polysaccharide gum water solution, and stirring for 30min to obtain soft material; 4. the prepared soft material is granulated, shot-blasted, dried and coated to obtain the pellet. The invention can improve the effective concentration of tilmicosin in the lung and increase the absorption metabolic rate and the utilization rate of the medicament.

Description

Traditional Chinese medicine targeted tilmicosin micro-pill and preparation method thereof
Technical Field
The invention belongs to the field of traditional Chinese veterinary medicines, and particularly relates to a traditional Chinese medicine targeted tilmicosin pellet and a preparation method thereof.
Background
Tilmicosin is a special antibiotic for livestock and poultry semi-synthesized by a hydrolysate of tylosin, and has an inhibiting effect on gram-positive bacteria, some gram-negative bacteria, mycoplasma, spirochetes and the like; has stronger antibacterial activity to actinobacillus pleuropneumoniae and pasteurella than tylosin, and is mainly used for preventing and treating livestock pneumonia (caused by infection of actinobacillus pleuropneumoniae, pasteurella, mycoplasma and the like), avian mycoplasmosis and mastitis of lactating animals. Tilmicosin belongs to macrolide antibiotics, and particularly has a 16-membered ring lactone structure, can be combined with a 50S subunit of a ribosome of bacteria, acts on a P site, inhibits the combination of transferase, thereby hindering the shift of mRNA, and preventing peptide bond from being shifted from an A site to a P site, thereby inhibiting the synthesis of protein and generating a bacteriostatic effect.
At present, tilmicosin has two administration routes, namely oral administration and subcutaneous injection, and the subcutaneous administration mode has complicated clinical application, large toxic and side effect and relatively less use; the main problems of the oral administration mode are that: 1) tilmicosin is bitter in taste and is easy to reduce the appetite of livestock and poultry, so that the feed intake of the livestock and poultry is greatly reduced, and 2) the effective medicine concentration reaching the lung lesion is low and unstable, so that the curative effect of the tilmicosin is influenced.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a traditional Chinese medicine targeted tilmicosin pellet and a preparation method thereof, which not only can cover the bitter taste of tilmicosin, but also can improve the effective concentration of the tilmicosin in the lung and increase the absorption metabolic rate and the utilization rate of the medicine.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
the first technical scheme is as follows:
a traditional Chinese medicine targeted tilmicosin pellet comprises the following raw materials in parts by weight:
Figure GDA0002930631060000011
further, the disintegrating agent is one or two of microcrystalline cellulose and sodium carboxymethyl cellulose.
Further, the disintegrant is microcrystalline cellulose.
Further, the adhesive is one or more of bletilla striata polysaccharide gum, dextrin and powdered sugar.
Further, the adhesive is bletilla striata polysaccharide gum.
Further, the filling agent is selected from one or two of astragalus polysaccharide and starch.
Further, the filler is selected from astragalus polysaccharide.
The second technical scheme is as follows:
a preparation method of a traditional Chinese medicine targeted tilmicosin pellet specifically comprises the following steps:
step 1, respectively crushing platycodon grandiflorum and pubescent holly root by using a jet mill, and sieving with a 350-mesh sieve to obtain superfine platycodon grandiflorum powder and superfine pubescent holly root powder for later use;
step 2, weighing the raw materials in parts by weight, and then mixing the raw materials in a mass ratio of the bletilla striata polysaccharide gum to the water of 2: 1, dissolving bletilla striata polysaccharide gum in water, and uniformly stirring to obtain a bletilla striata polysaccharide gum aqueous solution;
step 3, stirring tilmicosin, platycodon grandiflorum superfine powder, pubescent holly root superfine powder, microcrystalline cellulose and astragalus polysaccharide at the rotating speed of 60 revolutions per minute for 10 minutes, then adding the bletilla striata polysaccharide gum aqueous solution, and continuously stirring for 30 minutes to prepare a soft material;
and 4, granulating, shot blasting, drying and coating the prepared soft material to obtain the pellet.
Further, the step 4 specifically includes the following operations:
step 4-1, extruding and granulating the prepared soft material, and sieving with a 40-mesh sieve to obtain medicine granules;
step 4-2, performing shot blasting on the prepared medicine particles by using a shot blasting machine at the speed of 150 revolutions per minute until the pill cores are rounded, performing fluidized drying for 30 minutes, and naturally cooling to 45 ℃ to obtain the pill cores;
and 4-3, firstly dissolving the coating auxiliary materials by using a solvent to prepare a coating solution, then filling the cores into a multifunctional fluidized bed coating machine, and after the temperature of an air outlet is raised to 60 ℃, adding the cores and the coating auxiliary materials according to the mass ratio of the dry weight of the cores to the dry weight of the coating auxiliary materials of 8-15: 1, pumping the coating liquid into a spray gun through a peristaltic pump for spray coating (the frequency of the peristaltic pump is 70-80 times/min), and keeping the temperature of an air outlet at about 65 ℃ in the coating process; and after coating, continuously keeping the coating in a multifunctional fluidized bed coating machine for 15 minutes for drying.
Furthermore, the coating liquid comprises the following raw materials in parts by weight: 5-10 parts of coating auxiliary materials; solvent: 60 parts of absolute ethyl alcohol;
wherein the coating auxiliary material comprises 5-8 parts of hydroxypropyl methyl cellulose phthalate/polyacrylic resin; 1-3 parts of triethyl citrate; 1-2 parts of talcum powder.
Compared with the prior art, the invention has the beneficial effects that:
1. the invention adopts the radix platycodi as a targeting carrier, and the tilmicosin is introduced into the lung channel, so that the distribution of the tilmicosin in lung tissues is improved, the effective concentration of the tilmicosin in the lung is improved, and the bioavailability of the tilmicosin is improved; in addition, the platycodon grandiflorum can also effectively increase the solubility of the tilmicosin, so that the absorption utilization rate of the tilmicosin is increased.
2. According to the invention, the pubescent holly root has the effects of promoting blood circulation to remove blood stasis, and a large number of experiments prove that the pubescent holly root can cooperate with the platycodon root to promote the function of guiding the platycodon root to the channels, so that the effect of the platycodon root in improving the effective concentration of tilmicosin in the lung is obviously enhanced; the single use of the radix ilicis does not have the effect, the radix ilicis is probably related to the effect of promoting blood circulation and removing blood stasis of the pubescent holly root, changes the blood flow change of lung tissues and the whole body by promoting blood circulation and removing blood stasis, is more favorable for leading the platycodon root to the channels and increasing the concentration of tilmicosin entering the lung; thereby achieving the purpose of improving the effective concentration of the tilmicosin in the lung tissue and indirectly increasing the absorption metabolic rate and the utilization rate of the medicament. In addition, the platycodon grandiflorum and the pubescent holly root can also play a role in masking the taste, and the problem of entrance of tilmicosin is solved.
3. The platycodon grandiflorum and the pubescent holly root adopt superfine powder, the medicine granularity is smaller, the particle diameter of 350 meshes is 25 mu m, the cell diameter of plants is 10-100 mu m, and 350 meshes are selected, so that the medicine can achieve the effect of breaking the wall, and the medicine effect of the medicine can be better exerted.
4. The invention takes microcrystalline cellulose as a disintegrating agent, bletilla striata polysaccharide gum as an adhesive, astragalus polysaccharide as a filling agent and hydroxypropyl methyl cellulose phthalate, triethyl citrate, talcum powder and solvent absolute ethyl alcohol for coating, can realize the controlled release of the medicament, enables the medicament to be released and dissolved in intestinal tracts, and avoids medicament irritation and degradation caused by the release of the medicament in the stomach.
The platycodon grandiflorum and the pubescent holly root can improve the effective concentration of tilmicosin in the lung, meanwhile, the platycodon grandiflorum has the effects of relieving cough, reducing phlegm, ventilating the lung and relieving asthma, the pubescent holly root also has the effects of clearing heat and removing toxicity, the medicines are combined, the medicines have synergistic effect, the effects supplement each other, and the functions of treating the infection diseases of the lung of the pig (such as swine plague, asthma, blue ears and the like) are jointly realized.
Detailed Description
The present invention will be described in further detail with reference to examples.
Example 1
A traditional Chinese medicine targeted tilmicosin pellet comprises the following raw materials by weight:
Figure GDA0002930631060000031
the preparation method comprises the following steps:
and step 1, respectively crushing the platycodon grandiflorum and the pubescent holly root by using a jet mill, and sieving by using a 350-mesh sieve to obtain superfine platycodon grandiflorum powder and superfine pubescent holly root powder for later use.
Step 2, weighing the raw materials according to the weight ratio of the bletilla striata polysaccharide gum to the water of 2: 1, dissolving bletilla striata polysaccharide gum in water, and uniformly stirring to obtain a bletilla striata polysaccharide gum aqueous solution;
step 3, stirring tilmicosin, platycodon grandiflorum superfine powder, pubescent holly root superfine powder, microcrystalline cellulose and astragalus polysaccharide for 10 minutes at the rotating speed of 60 revolutions per minute by adopting a groove type mixer, then adding the bletilla striata polysaccharide gum aqueous solution, and continuously stirring for 30 minutes to prepare a soft material;
step 4, granulating, shot blasting, drying and coating the prepared soft material to obtain pellets;
step 4-1, extruding and granulating the prepared soft material, and sieving with a 40-mesh sieve to obtain medicine granules;
step 4-2, performing shot blasting on the prepared medicine particles by using a shot blasting machine at the speed of 150 revolutions per minute until the pill cores are rounded, performing fluidized drying for 30 minutes, and naturally cooling to 45 ℃ to obtain the pill cores;
step 4-3, dissolving coating auxiliary materials of hydroxypropyl methyl cellulose phthalate, triethyl citrate and talcum powder by using solvent absolute ethyl alcohol to prepare a coating solution, then loading the pellet core into a multifunctional fluidized bed coating machine, and after the temperature of an air outlet is raised to 60 ℃, adding the coating solution into the multifunctional fluidized bed coating machine according to the mass ratio of the dry weight of the pellet core to the dry weight of the coating auxiliary materials of 10: 1, pumping the coating liquid into a spray gun for spray coating through a peristaltic pump (the frequency of the peristaltic pump is 75 times/min), and keeping the temperature of an air outlet at about 65 ℃ in the coating process; and after coating, continuously keeping the coating in a multifunctional fluidized bed coating machine for 15 minutes for drying.
Example 2
A traditional Chinese medicine targeted tilmicosin pellet comprises the following raw materials by weight:
Figure GDA0002930631060000041
the preparation method comprises the following steps: the same as in example 1.
Example 3
A traditional Chinese medicine targeted tilmicosin pellet comprises the following raw materials by weight:
Figure GDA0002930631060000051
the preparation method comprises the following steps: the same as in example 1.
Comparative example 1
A traditional Chinese medicine targeted tilmicosin pellet comprises the following raw materials by weight:
Figure GDA0002930631060000052
the preparation method comprises the following steps:
step 1, crushing platycodon grandiflorum by using an airflow crusher, and sieving the crushed platycodon grandiflorum by using a 350-mesh sieve to obtain superfine platycodon grandiflorum powder for later use;
step 2, weighing the raw materials according to the weight ratio of the bletilla striata polysaccharide gum to the water of 2: 1, dissolving bletilla striata polysaccharide gum in water, and uniformly stirring to obtain a bletilla striata polysaccharide gum aqueous solution;
step 3, stirring tilmicosin, platycodon grandiflorum superfine powder, microcrystalline cellulose and astragalus polysaccharide for 10 minutes at the rotating speed of 60 revolutions/min by adopting a groove type mixer, then adding the bletilla striata polysaccharide gum aqueous solution, and continuously stirring for 30 minutes to prepare a soft material;
step 4, granulating, shot blasting, drying and coating the prepared soft material to obtain pellets;
step 4-1, extruding and granulating the prepared soft material, and sieving with a 40-mesh sieve to obtain medicine granules;
step 4-2, performing shot blasting on the prepared medicine particles by using a shot blasting machine at the speed of 150 revolutions per minute until the pill cores are rounded, performing fluidized drying for 30 minutes, and naturally cooling to 45 ℃ to obtain the pill cores;
step 4-3, dissolving coating auxiliary materials of hydroxypropyl methyl cellulose phthalate, triethyl citrate and talcum powder by using solvent absolute ethyl alcohol to prepare a coating solution, then loading the pellet core into a multifunctional fluidized bed coating machine, and after the temperature of an air outlet is raised to 60 ℃, adding the coating solution into the multifunctional fluidized bed coating machine according to the mass ratio of the dry weight of the pellet core to the dry weight of the coating auxiliary materials of 10: 1, pumping the coating liquid into a spray gun for spray coating through a peristaltic pump (the frequency of the peristaltic pump is 75 times/min), and keeping the temperature of an air outlet at about 65 ℃ in the coating process; and after coating, continuously keeping the coating in a multifunctional fluidized bed coating machine for 15 minutes for drying.
Comparative example 2
A traditional Chinese medicine targeted tilmicosin pellet comprises the following raw materials by weight:
Figure GDA0002930631060000061
the preparation method comprises the following steps:
step 1, crushing the pubescent holly root by using a jet mill, and sieving by using a 350-mesh sieve to obtain pubescent holly root superfine powder for later use.
Step 2, weighing the raw materials in parts by weight, and then mixing the raw materials in a mass ratio of the bletilla striata polysaccharide gum to the water of 2: 1, dissolving bletilla striata polysaccharide gum in water, and uniformly stirring to obtain a bletilla striata polysaccharide gum aqueous solution;
step 3, stirring tilmicosin, the pubescent holly root superfine powder, the microcrystalline cellulose and the astragalus polysaccharide for 10 minutes at the rotating speed of 60 revolutions per minute by adopting a groove type mixer, then adding the bletilla polysaccharide gum aqueous solution, and continuously stirring for 30 minutes to prepare a soft material;
step 4, granulating, shot blasting, drying and coating the prepared soft material to obtain pellets;
step 4-1, extruding and granulating the prepared soft material, and sieving with a 40-mesh sieve to obtain medicine granules;
step 4-2, performing shot blasting on the prepared medicine particles by using a shot blasting machine at the speed of 150 revolutions per minute until the pill cores are rounded, performing fluidized drying for 30 minutes, and naturally cooling to 45 ℃ to obtain the pill cores;
step 4-3, dissolving coating auxiliary materials of hydroxypropyl methyl cellulose phthalate, triethyl citrate and talcum powder by using solvent absolute ethyl alcohol to prepare a coating solution, then loading the pellet core into a multifunctional fluidized bed coating machine, and after the temperature of an air outlet is raised to 60 ℃, adding the coating solution into the multifunctional fluidized bed coating machine according to the mass ratio of the dry weight of the pellet core to the dry weight of the coating auxiliary materials of 10: 1, pumping the coating liquid into a spray gun for spray coating through a peristaltic pump (the frequency of the peristaltic pump is 75 times/min), and keeping the temperature of an air outlet at about 65 ℃ in the coating process; and after coating, continuously keeping the coating in a multifunctional fluidized bed coating machine for 15 minutes for drying.
Comparative example 3
A traditional Chinese medicine targeted tilmicosin pellet comprises the following raw materials by weight:
Figure GDA0002930631060000071
the preparation method comprises the following steps:
step 1, crushing the white mulberry root-bark by using a pneumatic crusher, and sieving the crushed white mulberry root-bark by using a 350-mesh sieve to obtain white mulberry root-bark superfine powder for later use.
Step 2, weighing the raw materials according to the weight ratio of the bletilla striata polysaccharide gum to the water of 2: 1, dissolving bletilla striata polysaccharide gum in water, and uniformly stirring to obtain a bletilla striata polysaccharide gum aqueous solution;
step 3, stirring tilmicosin, the white mulberry root-bark superfine powder, the microcrystalline cellulose and the astragalus polysaccharide for 10 minutes at the rotating speed of 60 revolutions per minute by adopting a groove type mixer, then adding the bletilla polysaccharide gum aqueous solution, and continuously stirring for 30 minutes to prepare a soft material;
step 4, granulating, shot blasting, drying and coating the prepared soft material to obtain pellets;
step 4-1, extruding and granulating the prepared soft material, and sieving with a 40-mesh sieve to obtain medicine granules;
step 4-2, performing shot blasting on the prepared medicine particles by using a shot blasting machine at the speed of 150 revolutions per minute until the pill cores are rounded, performing fluidized drying for 30 minutes, and naturally cooling to 45 ℃ to obtain the pill cores;
step 4-3, dissolving coating auxiliary materials of hydroxypropyl methyl cellulose phthalate, triethyl citrate and talcum powder by using solvent absolute ethyl alcohol to prepare a coating solution, then loading the pellet core into a multifunctional fluidized bed coating machine, and after the temperature of an air outlet is raised to 60 ℃, adding the coating solution into the multifunctional fluidized bed coating machine according to the mass ratio of the dry weight of the pellet core to the dry weight of the coating auxiliary materials of 10: 1, pumping the coating liquid into a spray gun for spray coating through a peristaltic pump (the frequency of the peristaltic pump is 75 times/min), and keeping the temperature of an air outlet at about 65 ℃ in the coating process; and after coating, continuously keeping the coating in a multifunctional fluidized bed coating machine for 15 minutes for drying.
Comparative example 4
A traditional Chinese medicine targeted tilmicosin pellet comprises the following raw materials by weight:
Figure GDA0002930631060000081
the preparation method comprises the following steps:
step 1, weighing the raw materials according to the weight ratio of the bletilla striata polysaccharide gum to the water of 2: 1, dissolving bletilla striata polysaccharide gum in water, and uniformly stirring to obtain a bletilla striata polysaccharide gum aqueous solution;
step 2, stirring tilmicosin, microcrystalline cellulose and astragalus polysaccharide for 10 minutes at the rotating speed of 60 revolutions per minute by adopting a groove type mixer, then adding the bletilla striata polysaccharide gum aqueous solution, and continuously stirring for 30 minutes to prepare a soft material;
step 3, granulating, shot blasting, drying and coating the prepared soft material to obtain pellets;
step 3-1, extruding and granulating the prepared soft material, and sieving with a 40-mesh sieve to obtain medicine granules;
step 3-2, performing shot blasting on the prepared medicine particles by using a shot blasting machine at the speed of 150 revolutions per minute until the pill cores are rounded, performing fluidized drying for 30 minutes, and naturally cooling to 45 ℃ to obtain the pill cores;
3-3, dissolving coating auxiliary materials of hydroxypropyl methyl cellulose phthalate, triethyl citrate and talcum powder by using solvent absolute ethyl alcohol to prepare a coating solution, then loading the pellet core into a multifunctional fluidized bed coating machine, and after the temperature of an air outlet is raised to 60 ℃, adding the coating solution into the multifunctional fluidized bed coating machine according to the mass ratio of the dry weight of the pellet core to the dry weight of the coating auxiliary materials of 10: 1, pumping the coating liquid into a spray gun for spray coating through a peristaltic pump (the frequency of the peristaltic pump is 75 times/min), and keeping the temperature of an air outlet at about 65 ℃ in the coating process; and after coating, continuously keeping the coating in a multifunctional fluidized bed coating machine for 15 minutes for drying.
Effect example 1: time curve of lung
Firstly, sampling:
the healthy pigs are divided into 5 groups at random, wherein the groups are respectively a test group, a comparison two group, a comparison three group and a comparison four group, and tilmicosin is respectively expressed according to the weight per kilogram: feeding tilmicosin at a dosage of 40mg/kg (feed additive dosage is 400mg/kg) with a dosage (each test group and a control group are fed with the dosage converted according to the actual content of the tilmicosin), slaughtering at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 and 96h after feeding, aseptically taking lung tissues, washing the lung tissues with normal saline, cutting the lung tissues into small pieces, homogenizing by a high-speed homogenizer at 12000rpm, freezing and storing at the temperature of-20 ℃, and measuring the content of the tilmicosin, wherein the curve data of the drug administration is shown in table 1.
Two, grouping situation
One set of experiments was: the pellets prepared in example 1 were used for administration;
comparing one group: the pellets prepared in comparative example 1 were used for administration;
two groups are compared: the pellets prepared in comparative example 2 were used for administration;
three groups were compared: the pellets prepared in comparative example 3 were used for administration;
four groups were compared: the pellets prepared in comparative example 4 were used for administration;
thirdly, a tilmicosin determination method: adopting an HPLC method; the method comprises the following specific steps:
1. sample pretreatment:
weighing 5.0g of lung tissue, placing the lung tissue in a 50ml polypropylene centrifugal tube, adding 8ml of acetonitrile, whirling and uniformly mixing, shaking at a medium speed for 30min, centrifuging at 3000rpm for 10min, taking supernatant liquid to place in a 100ml centrifugal tube, respectively adding 5ml of potassium dihydrogen phosphate buffer solution and 8ml of acetonitrile into tissue clots, stirring to disperse the tissue clots, whirling and uniformly mixing, shaking at a medium speed for 30min, centrifuging at 3000rpm for 10min, combining the two supernatants in a 100ml centrifugal tube, adding 40ml of water, centrifuging at 3000rpml for 10min, taking supernatant liquid to place in a proper amount of container, adding 10ml of water, uniformly mixing, and passing through an SPE column.
Passing the extract through SPE column, activating with 10ml methanol and balancing SPE column with 10ml purification, adjusting vacuum pump pressure to make flow rate not too fast when sample passes SPE column, keeping flow rate stable, washing with 25% acetonitrile-pure water-pure acetonitrile washing method with flow rate of 1 drop/second, drying SPE column for at least 5min after acetonitrile flows out from SPE column, eluting with 2.5ml eluent in graduated tube, evaporating to dryness with rotary evaporator, diluting mobile phase to constant volume to 1ml, vortexing for 30s, standing for 15min, filtering with 0.22 micron pinhole type filter membrane, taking 20 microliter to HPLC analysis.
2. Chromatographic conditions are as follows:
a chromatographic column: c18 chromatographic column 150 x 4.6mm 5 μm
Mobile phase: acetonitrile: tetrahydrofuran: dibutylamine phosphate buffer: water 130:55:25:790
Flow rate: 0.7ml/min
Column temperature: 30 deg.C
TABLE 1
Figure GDA0002930631060000101
The results show that: compared with four groups, one group, two groups and three groups, the drug concentration of tilmicosin in lung tissues is obviously lower than that of one group, so that the ilex pubescens can be proved to be capable of cooperating with the platycodon grandiflorum to promote the meridian tropism of the platycodon grandiflorum as an introduction agent, and the effect of the platycodon grandiflorum on improving the effective concentration of the tilmicosin in the lung is obviously enhanced. In addition, the control group reached a peak in blood at 2 hours, which may be due to altered blood flow, but the overall effect was still inferior to that of the control and test groups.
Effect example 2: release Profile
The operational procedures described in appendix 160 in the veterinary pharmacopoeia of 2015 edition were used to determine the drug dissolution and release rates, and the pellets prepared in example 1 were subjected to disintegration tests, the release curve data of which are shown in table 2;
TABLE 2
Figure GDA0002930631060000102
As can be seen from the table, the prepared enteric-coated pellets can realize local release and reach the quality standard of enteric-coated preparations.
Effect example 3: clinical trial effect analysis
The clinical naturally-occurring pig herd, 116 fattening pigs, part of the body temperature is raised, cough and asthma occur, and foam-like liquid flows out of the mouth and the nose; dyspnea into a dog sitting posture; inflammatory swelling of the neck and throat; c, performing autopsy: the subcutaneous, thoracic and pericardial cavities are filled with fluid; bleeding and swelling of liver, lung, lymph nodes; the section of lung is marbled; the swine plague is diagnosed, the 104 surviving pigs are randomly divided into 4 groups, the groups are respectively treated by administration, the dosage is 400mg of tilmicosin per kilogram of feed additive, the whole group of the feed is administered by mixing, the treatment result is recorded, the treatment result is shown in the following table 3 and table 4, and during administration, each test group and each comparison group are administered by converting the actual content of the tilmicosin.
Grouping condition: see table below;
one set of experiments was: the pellets prepared in example 1 were used for administration;
comparing one group: the pellets prepared in comparative example 1 were used for administration;
two groups are compared: the pellets prepared in comparative example 4 were used for administration;
conventional drug groups: tilmicosin powder.
TABLE 3
Grouping Total number of heads Number of clinical symptoms Assume healthy head count
Test group 26 heads 15 heads 11 heads
Compare a group 26 heads 13 heads 13 heads
Comparison of two groups 26 heads 13 heads 13 heads
Conventional drug group 26 heads 12 heads 14 heads
TABLE 4
Grouping Effective in prevention (head) High efficiency Number of heads cured Cure rate Time to cure
Test A set 11 heads 100% 15 heads 100% 3 days
Compare a group 13 heads 100% 12 heads 92.3% 4 days
Comparison of two groups 12 heads 92.3% 11 heads 84.6% 5 days
Conventional drug group 11 heads 91.7% 11 heads 78.6% 7 days
The experimental results show that the experimental group has optimal effect, the treatment effective rate, the cure rate and the time required for curing are all superior to the comparison group lacking the pubescent holly root and the common pellet group lacking the platycodon grandiflorum and the pubescent holly root, and the experimental group can prove that the platycodon grandiflorum, the pubescent holly root and the tilmicosin can take effect synergistically, so that the treatment effect is obviously improved, the treatment time is greatly shortened, and the experimental group can be possibly related to the effect that the pubescent holly root and the platycodon grandiflorum can cooperate to promote the radix platycodonis to have the effect of guiding drugs to the channels. Compared with the conventional medicine group, the two groups have better treatment effective rate, which is probably related to the following factors, after coating, 1) the feed intake is improved, the factors that some pigs do not take feed due to the addition of tilmicosin are reduced, 2) the medicine irritation and degradation phenomena caused by the release of the tilmicosin in the stomach are reduced, and the clinical effect is higher than that of the common coated pellet.
The embodiments described above are only preferred embodiments of the invention and are not exhaustive of the possible implementations of the invention. Any obvious modifications to the above would be obvious to those of ordinary skill in the art, but would not bring the invention so modified beyond the spirit and scope of the present invention.

Claims (7)

1. A traditional Chinese medicine targeted tilmicosin pellet is characterized by comprising the following raw materials in parts by weight:
Figure FDA0002945297260000011
2. the traditional Chinese medicine targeted tilmicosin pellet as claimed in claim 1, wherein the disintegrant is one or both of microcrystalline cellulose and sodium carboxymethylcellulose.
3. The traditional Chinese medicine targeted tilmicosin pellet as claimed in claim 1, wherein the adhesive is one or more of bletilla polysaccharide gum, dextrin and powdered sugar.
4. The traditional Chinese medicine targeted tilmicosin pellet as claimed in claim 1, wherein the filler is one or two selected from astragalus polysaccharides and starch.
5. The preparation method of the traditional Chinese medicine targeted tilmicosin pellet according to claim 1, which is characterized by comprising the following steps:
step 1, respectively crushing platycodon grandiflorum and pubescent holly root by using a jet mill, and sieving with a 350-mesh sieve to obtain superfine platycodon grandiflorum powder and superfine pubescent holly root powder for later use;
step 2, weighing the raw materials in parts by weight, and then mixing the raw materials in a mass ratio of the adhesive to water of 2: 1, dissolving the adhesive by using water, and uniformly stirring to obtain an adhesive aqueous solution;
step 3, stirring tilmicosin, platycodon grandiflorum superfine powder, pubescent holly root superfine powder, disintegrating agent and filler at the rotating speed of 60 revolutions per minute for 10 minutes, then adding the adhesive aqueous solution, and continuously stirring for 30 minutes to prepare a soft material;
step 4, granulating, shot blasting, drying and coating the prepared soft material to obtain pellets;
the adhesive is bletilla striata polysaccharide gum;
the disintegrating agent adopts microcrystalline cellulose;
the filler is astragalus polysaccharide.
6. The method for preparing a traditional Chinese medicine targeted tilmicosin pellet as claimed in claim 5, wherein the step 4 specifically comprises the following operations:
step 4-1, extruding and granulating the prepared soft material, and sieving with a 40-mesh sieve to obtain medicine granules;
step 4-2, performing shot blasting on the prepared medicine particles by using a shot blasting machine at the speed of 150 revolutions per minute until the pill cores are rounded, performing fluidized drying for 30 minutes, and naturally cooling to 45 ℃ to obtain the pill cores;
and 4-3, firstly dissolving the coating auxiliary materials by using a solvent to prepare a coating solution, then filling the cores into a multifunctional fluidized bed coating machine, and after the temperature of an air outlet is raised to 60 ℃, adding the cores and the coating auxiliary materials according to the mass ratio of the dry weight of the cores to the dry weight of the coating auxiliary materials of 8-15: 1, pumping the coating liquid into a spray gun through a peristaltic pump for spray coating, and keeping the temperature of an air outlet at 65 ℃ in the coating process; and after coating, continuously keeping the coating in a multifunctional fluidized bed coating machine for 15 minutes for drying.
7. The preparation method of the traditional Chinese medicine targeted tilmicosin pellet as claimed in claim 6, wherein the coating solution comprises the following raw materials in parts by weight: 5-10 parts of coating auxiliary materials; solvent: 60 parts of absolute ethyl alcohol;
wherein the coating auxiliary material comprises 3-8 parts of hydroxypropyl methyl cellulose phthalate or polyacrylic resin; 1-3 parts of triethyl citrate; 1-2 parts of talcum powder.
CN201811418549.7A 2018-11-26 2018-11-26 Traditional Chinese medicine targeted tilmicosin micro-pill and preparation method thereof Active CN109364042B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201811418549.7A CN109364042B (en) 2018-11-26 2018-11-26 Traditional Chinese medicine targeted tilmicosin micro-pill and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201811418549.7A CN109364042B (en) 2018-11-26 2018-11-26 Traditional Chinese medicine targeted tilmicosin micro-pill and preparation method thereof

Publications (2)

Publication Number Publication Date
CN109364042A CN109364042A (en) 2019-02-22
CN109364042B true CN109364042B (en) 2021-04-02

Family

ID=65377084

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201811418549.7A Active CN109364042B (en) 2018-11-26 2018-11-26 Traditional Chinese medicine targeted tilmicosin micro-pill and preparation method thereof

Country Status (1)

Country Link
CN (1) CN109364042B (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103006892A (en) * 2012-12-28 2013-04-03 北京大北农动物保健科技有限责任公司 Medicine composition for preventing and treating porcine viral diseases, and premix and batch with composition
CN104784123A (en) * 2015-03-19 2015-07-22 湖南九鼎科技(集团)有限公司兽药分公司 Process for preparing tilmicosin enteric-coated pellet by centrifuge method
WO2015138042A2 (en) * 2014-03-14 2015-09-17 Bovicor Pharmatech Inc. Nitric oxide treatment of bovine respiratory disease complex and other respiratory conditions
CN105125524A (en) * 2015-10-20 2015-12-09 中牧南京动物药业有限公司 Tilmicosin enteric-coated pellets and preparation method thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103006892A (en) * 2012-12-28 2013-04-03 北京大北农动物保健科技有限责任公司 Medicine composition for preventing and treating porcine viral diseases, and premix and batch with composition
WO2015138042A2 (en) * 2014-03-14 2015-09-17 Bovicor Pharmatech Inc. Nitric oxide treatment of bovine respiratory disease complex and other respiratory conditions
CN104784123A (en) * 2015-03-19 2015-07-22 湖南九鼎科技(集团)有限公司兽药分公司 Process for preparing tilmicosin enteric-coated pellet by centrifuge method
CN105125524A (en) * 2015-10-20 2015-12-09 中牧南京动物药业有限公司 Tilmicosin enteric-coated pellets and preparation method thereof

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
中草药在促进西药吸收和提高血药浓度方面的作用;胡金山等;《药学进展》;20081231;第32卷(第5期);第207-211页 *
中药桔梗对替米考星在肺脏中药物浓度的影响;边涛等;《畜牧兽医学报》;20131231;第44卷(第6期);第983页左栏第3段 *
桔梗对替米考星在肺脏中药物浓度的影响;边涛;《中国优秀硕士学位论文全文数据库 农业科技辑》;20140315(第3期);第20页第4.4.2节、第21页第4.5节 *

Also Published As

Publication number Publication date
CN109364042A (en) 2019-02-22

Similar Documents

Publication Publication Date Title
CN101690717B (en) Valnemulin for livestock and saline premix and preparation method thereof
CN102188422B (en) Compound florfenicol injection and preparation method and application thereof
CN110075082B (en) Enrofloxacin quick-release pellet and preparation method thereof
CN109364042B (en) Traditional Chinese medicine targeted tilmicosin micro-pill and preparation method thereof
CN104257794B (en) Chinese medicine composition of a kind of spleen reinforcing removing food stagnancy and preparation method thereof
CN103622919A (en) Tilmicosin phosphate enteric granules and preparation method thereof
CN107375247B (en) Tilmicosin film-controlled enteric sustained-release preparation and preparation method thereof
CN111407728B (en) Tilmicosin enteric solid dispersion and preparation method and application thereof
CN116139257A (en) Traditional Chinese medicine formula for treating postpartum hypogalactia of sow and preparation method thereof
CN104586875A (en) Preparation method for compound tilmicosin enteric-coated granules
CN103705715B (en) Preparation method of powder for clearing lung-heat micropill for animals and products thereof
CN108969648B (en) Pharmaceutical composition and application method thereof
CN103083396A (en) Formula and preparation method of traditional Chinese medicine granule for prevention and treatment of cow subclinical mastitis
CN111603448A (en) Compound doxycycline hydrochloride soluble powder and preparation method thereof
CN106362159A (en) Molecular skeleton type tilmicosin sustained release preparation and preparation method thereof
CN116531426B (en) Sulfur-containing protamine pharmaceutical composition for preventing and treating leucopenia caused by chemotherapy and preparation method thereof
CN110279796A (en) A kind of Chinese veterinary medicinal composition and preparation method thereof for preventing and treating porcine mycoplasmal pneumonia
WO2021103240A1 (en) Soluble granule for improving pig immunity and method for preparation thereof
CN103656037A (en) Traditional Chinese medicine composition with effects of regulating vital energy and relaxing bowel for livestock and preparation method thereof
CN101543526A (en) Kudzu root total aglycone sustained-release pellet as well as preparation method and application thereof
CN102379945B (en) Veterinary compound Chinese-western drug composition for defervescing and diminishing inflammation
CN106880686B (en) Traditional Chinese medicine premix for preventing and treating piglet diarrhea and preparation method thereof
CN108771726B (en) Traditional Chinese medicine compound for preventing and treating livestock and poultry diarrhea and preparation process thereof
CN113546155A (en) Chinese and western medicine compound preparation containing tulathromycin and preparation method thereof
CN107137665B (en) Traditional Chinese medicine composition for preventing and treating myocardial fibrosis and application thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
EE01 Entry into force of recordation of patent licensing contract

Application publication date: 20190222

Assignee: Beijing Leguan Pet Products Co.,Ltd.

Assignor: HEBEI DEPOND ANIMAL HEALTH TECHNOLOGY CO.,LTD.

Contract record no.: X2023980036556

Denomination of invention: A Chinese medicine targeted Tilmicosin pellets and its preparation method

Granted publication date: 20210402

License type: Common License

Record date: 20230613

EE01 Entry into force of recordation of patent licensing contract