Description

translated from Chinese

取硝呋酚酰肼20kg碾碎过900目筛得细粉，与IOkg腐植酸钠350目细粉混合均匀，用
干式制粒机直接压制成颗粒，颗粒的粒度为85〜100目，把所制得的硝呋酚酰肼颗粒
与粒度为85〜100目的玉米芯粉70kg投入到300立升的三维混合搅拌机中，搅拌混合
均匀，测得变异系数< 5%后停止搅拌，即得到成品硝呋酚酰肼预混剂。

A method for preparing ranitidine phenolic hydrazide premixes

FIELD

[0001] The present invention relates to the technical field of veterinary premixes,
particularly relates to a method for preparing ranitidine phenolic hydrazide premixes.

Background technique

[0002] ranitidine sprinkle hydrazide (Nifuroxazide), also known as ranitidine gliclazide, in

human medicine as antitumor nitrofurans, for the treatment of colitis, and
diarrhea. Ranitidine phenolic hydrazides broad antibacterial spectrum, a high antibacterial
activity, low inhibitory concentration, and sulfonamides, quinolones, and no cross-
resistance to other antibiotics, antibacterial activity which is hardly affected by other
organic matter, stable effect. Since the product can effectively prevent poultry E. coli,
Salmonella, Pasteurella, anatipestifer, aerogenes, Proteus, Staphylococcus aureus and
Bacillus necrotic intestinal or urinary tract disease caused, can prevent diarrhea and
promote animal feed, the EC is the only legal new high specific animal feed additive. China
in recent years are also veterinary drugs and feed additives manufacturing enterprises to
develop applications in major veterinary clinic for the prevention and treatment of
coccidiosis in chickens, white blood cells caused by protozoa of the white crown disease
and cecal hepatitis and other diseases, for bacteria, vibrio in aquatic animals and intestinal
and systemic fungal disease, susceptibility effect in water is much higher than other
antimicrobial agents. In the feed additives industry, mainly for pigs, chickens and aquatic
animal feed additive force the mouth, it can be effective in preventing diarrhea, promoting
animal feed.

[0003] hydrazide ranitidine phenol, 4-hydroxy _2'_ its chemical name is (5-nitro-furan-
methylene) - phenyl hydrazide, or bright yellow as a yellow powder, is generally insoluble
in water or sparingly soluble water, mostly domestic content of> 98.5% of the drug
substance and content of 20% active ingredient supply market, due to the low water
solubility of the product, resulting in poor dispersion, low bioavailability, affecting the full
efficacy of.
[0004] The humic acid (HA) is in the animal and plant residues action of microorganisms,
the first decomposed into a relatively simple organic compound A and then by
condensation to form amorphous polymer compound. Modern research has found that more
functional groups containing a carboxyl group, a carbonyl group, quinone group, phenol
group HA molecules, which determine the activity of the gene having humic properties
weakly acidic, hydrophilic, complexation and adsorption and the like. In addition, the HA
determines contains amino acids, vitamins, enzymes and trace elements, and have strong
antibacterial, antiviral, anti-inflammatory, hemostatic, improve microcirculation, anti-
tumor, in vivo regulation of the immune and endocrine function.

Sodium [0005] The sodium salt of humic acid is a humic acid, is extracted from weathered
coal a polymer organic weak acid salts of weak, black colloid. It is a commercially
available product or dark brown shiny dark gray particulate or powder. Its chemical
structure is a complex structure of benzene carbon, hydrogen, oxygen, nitrogen, sulfur and
other elements consisting of quinones, pyrrole, pyrazole instigate, furanyl, semiquinone
groups, an alcoholic hydroxyl group, hydroxyquinone, enol group, sulfonamide group,
amino and hydroxyl functional groups, and therefore there is a strong chelating power
network together and, at the same time there is a strong ion exchange and
adsorption. According to the literature, sodium humate rich in vitamins, antibiotics,
alkaloids, and physiologically active substances to the phenolic, quinone active groups can
promote the activity of digestive enzymes, stimulate digestion animals, additives for animal
husbandry, weight gain can improve animal performance. There results show that the
healthy growth of pigs fed with sodium humate, T lymphocytes and B lymphocytes have
activity was affected. T lymphocytes, B lymphocytes are the main animal
immunocompetent cells, which may lead to enhanced activity of the body's cellular and
humoral immune elevated levels, so as to promote ( "China Feed Products and
Technologies Almanac" improve immunity 2008--2009 year 321-322P).

[0006] Modern poultry pharmaceutically describes humic acid having a hemostatic, anti-
inflammatory, sedative, analgesic, astringent, anti-allergy, to rot myogenic, adjust the
gastrointestinal function and so, can be used in oral acute gastroenteritis, diarrhea,
dysentery, gastrointestinal ulcers, the efficacy of horses, mules really indigestion, enteritis
of calves is also a valuable adjunct to therapy. Its palatability, prevention and treatment of
specific and nonspecific dysentery and diarrhea have good results. Humic acid sodium is a
development value of the feed additive (Yan Jiye · Animal Drug Handbook, Golden Shield
Press, November 2007 3rd revised edition, 543P).

[0007] The object of the present invention is by ranitidine phenolic hydrazides crushed to
800~1000 mesh powder, and further having improved immunity of livestock and poultry, to
rot myogenic, gastrointestinal function adjustment function Complex of sodium humate
premix of a new product, object of ranitidine by finely pulverized phenol hydrazide, drug
dispersion performance can be increased while better enables the uniform distribution of
the feed, poultry and aquatic animal to improve drug absorption and utilization, improve
bioavailability, improve the effect of the drug used. Retrieved, yet related projects such as
reports and patent applications.

SUMMARY
[0008] The object of the present invention is less than for the prior art products, there is
provided a method for preparing ranitidine phenolic hydrazide premixes, improve product
results.

[0009] The object of the present invention is to be implemented by the following scheme.

[0010] A method for preparing ranitidine phenolic hydrazides premix comprises the
following process steps:

(1) First ranitidine phenolic hydrazides crushed through 800~1000 mesh sieve, 350 mesh
powder and decay values sodium mixed, compressed with a dry granulator directly into
particles, a particle size of 85~100 mesh the weight ratio of the mixture of phenol hydrazide
ranitidine sodium humate powder is I: 0 5~I;.

(2) The phenol obtained ranitidine hydrazide and sodium humate composite particles with a
particle size of 85~100 object of the carrier material into the mixer and the amount of the
phenolic hydrazide of ranitidine it should ranitidine in phenolic hydrazide content premix is
5~20% by weight, uniformly stirred to obtain the finished product after ranitidine phenolic
hydrazide premixes.

[0011] The dry granulator using dry granulation commonly used machines, tableting in a
pelletizer, cutting, discharge, sieving process.

Vector [0012] The carrier may be an organic and / or inorganic carrier, the carrier is
organic beans Bo flour, wheat bran, rice bran, starch, corn flour or corn cobs; inorganic
carrier is calcium carbonate, shell powder, or zeolite powder.

[0013] beneficial effects

I, the product of the present invention a phenolic hydrazides ranitidine after pulverization,
dispersion area is large, widely distributed, poultry and fish can be increased absorption and
utilization of drugs, improve bioavailability, improve the effect of the drug used.

[0014] 2, sodium humate product of the invention has a good adsorption, and with
ranitidine phenolic hydrazide dry granulator directly compressed into a dense,
homogeneous granules, good fluidity, facilitates distributed during use mix well.

[0015] 3, ranitidine phenolic hydrazide premix prepared fine spherical particles of the
present invention, the flowability and improving the dispersibility, and therefore, it is
mixed with the feed is also improved, so that it can obtain a uniform the mixture, which
will help the process of livestock and poultry feed their dose of balance.

[0016] 4, the product of the present invention, since with addition of sodium humate, not
only improve the immunity of livestock and poultry, more conducive suffering from acute
gastroenteritis, diarrhea, dysentery, peptic ulcer livestock and aquatic animal treatment,
help adjust gastrointestinal function.
[0017] 5. The method of preparing products of the invention is simple, reliable process,
stable performance, ranitidine phenolic hydrazide prepared by the process of the present
invention is fully in line with premixes "China Veterinary Pharmacopoeia" and "veterinary
quality standard" requirements. Suitable for industrial production.

Detailed ways

[0018] The following embodiments in conjunction with embodiments of the present

invention will be described in further detail, but they are not limitative of the present
invention. [0019] Example I

Take 5kg ranitidine phenolic hydrazides crushed through 800 mesh sieve to obtain powder,
and sodium humate 2. 5kg mixed powder 350 mesh, with a dry direct compression
granulator into granules, a particle size of 85~100 mesh , prepared in the phenol ranitidine
granules with a particle size of hydrazide 85~100 object bean powder 92. 5kg Bo into three
300-liter mixer, the mixing evenly, measured coefficient of variation <5% after the stirring
was stopped , i.e., to obtain a phenolic hydrazide finished ranitidine premixes.

[0020] Example 2

Take 5kg ranitidine phenolic hydrazides crushed through 800 mesh sieve to obtain powder,
and 350 mesh powder 3kg sodium humate mixed, compressed with a dry granulator
directly into particles, a particle size of 85~100 mesh, the the resulting phenolic hydrazide
ranitidine particles and a particle size of 85~100 bran 92kg object into 300 liters of a three-
dimensional mixer, the mixing evenly, measured coefficient of variation <4% after stirring
was stopped, to obtain finished nitro furosemide phenolic hydrazide premixes.

[0021] Example 3

Take 5kg ranitidine phenolic hydrazides crushed through 900 mesh sieve to obtain powder,
and sodium humate 3. 5kg mixed powder 350 mesh, with a dry direct compression
granulator into granules, a particle size of 85~100 mesh , prepared in the phenol ranitidine
granules with a particle size of hydrazide 85~100 object 91. 5kg of rice bran into three 300-
liter mixer, the mixing evenly, measured coefficient of variation <5% after stirring was
stopped, i.e., ranitidine be finished phenolic hydrazide premixes.

[0022] Example 4

Take 5kg ranitidine phenolic hydrazides crushed through 900 mesh sieve to obtain powder,
and 350 mesh powder 4kg sodium humate mixed, compressed with a dry granulator
directly into particles, a particle size of 85~100 mesh, the the resulting phenolic hydrazide
ranitidine particles and a particle size of 85~100 object 91kg starch into 300 liters of a
three-dimensional mixer, uniformly stirred and mixed, measured coefficient of variation
<4% after stirring was stopped, to obtain the finished product ranitidine phenolic hydrazide
premixes.
[0023] Example 5

Take 5kg ranitidine phenolic hydrazides crushed through 900 mesh sieve to obtain powder,
and sodium humate 4. 5kg mixed powder 350 mesh, with a dry direct compression
granulator into granules, a particle size of 85~100 mesh , prepared in the phenol ranitidine
granules with a particle size of hydrazide 85~100 object 90. 5kg corn flour into 300 liters of
a three-dimensional mixer, the mixing evenly, measured coefficient of variation <3% after
stirring was stopped, i.e., obtain a finished ranitidine phenolic hydrazide premixes.

[0024] Example 6

Take 5kg ranitidine phenolic hydrazides crushed through 800 mesh sieve to obtain powder,
and sodium humate 5kg 350 mesh powder mixed, compressed with a dry granulator
directly into particles, a particle size of 85~100 mesh, the the resulting phenolic hydrazide
ranitidine particles and a particle size of 85~100 90kg object corncob into 300 liters of a
three-dimensional mixer, the mixing evenly, measured coefficient of variation <5% after
stirring was stopped, to obtain the finished product ranitidine phenolic hydrazide premixes.

[0025] Example 7

Take ranitidine phenolic hydrazides IOkg crushed powder obtained through the 1000-mesh
sieve, and 350 mesh powder 5kg sodium humate mixed, compressed with a dry granulator
directly into particles, a particle size of 85~100 mesh, the the resulting phenolic hydrazide
ranitidine particles and the calcium carbonate particle size of 85~100 object of 85kg into
300 liters of a three-dimensional mixer, the mixing evenly, measured coefficient of
variation <3% after stirring was stopped, to obtain finished nitro furosemide phenolic
hydrazide premixes.

[0026] Example 8

Take ranitidine phenolic hydrazides IOkg crushed through 1000 mesh sieve to obtain
powder, and sodium humate IOkg 350 mesh powder mixed, compressed with a dry
granulator directly into particles, a particle size of 85~100 mesh, the the resulting phenolic
hydrazide ranitidine particles and a particle size of 85~100 object of the zeolite powder 300
liters 80kg into a three-dimensional mixer, the mixing evenly, measured coefficient of
variation <5% after stirring was stopped, to obtain finished nitro furosemide phenolic
hydrazide premixes.

[0027] Example 9

Take 15kg ranitidine phenolic hydrazides crushed through 800 mesh sieve to obtain
powder, and sodium humate 7. 5kg mixed powder 350 mesh, with a dry direct compression
granulator into granules, a particle size of 85~100 mesh , prepared in the phenol ranitidine
granules with a particle size of hydrazide 85~100 object corncob 77. 5kg into three 300-
liter mixer, the mixing evenly, measured coefficient of variation <5% after the stirring was
stopped , i.e., to obtain a phenolic hydrazide finished ranitidine premixes.
[0028] Example 10

Take 15kg ranitidine phenolic hydrazides crushed through 1000 mesh sieve to obtain
powder, and 15kg sodium humate 350 mesh powder mixed, compressed with a dry
granulator directly into particles, a particle size of 85~100 mesh, the the resulting phenolic
hydrazide ranitidine particles and the calcium carbonate particle size of 85~100 object of
70kg into 300 liters of a three-dimensional mixer, the mixing evenly, measured coefficient
of variation <3% after stirring was stopped, to obtain finished nitro furosemide phenolic
hydrazide premixes.

[0029] Example 11

Take 20kg ranitidine phenolic hydrazides crushed through 900 mesh sieve to obtain
powder, and sodium humate IOkg 350 mesh powder mixed with a dry direct compression
granulator into granules, a particle size of 85~100 mesh, the the resulting phenolic
hydrazide ranitidine particles and a particle size of 85~100 70kg object corncob into 300
liters of a three-dimensional mixer, the mixing evenly, measured coefficient of variation
<5% after stirring was stopped, to obtain the finished product ranitidine phenolic hydrazide
premixes.

[0030] Example 12

Take 20kg ranitidine phenolic hydrazides crushed through 800 mesh sieve to obtain
powder, and 20kg sodium humate 350 mesh powder mixed with a dry direct compression
granulator into granules, a particle size of 85~100 mesh, the the resulting phenolic
hydrazide ranitidine particles and a particle size of 85~100 60kg object corncob into 300
liters of a three-dimensional mixer, the mixing evenly, measured coefficient of variation
<5% after stirring was stopped, to obtain the finished product ranitidine phenolic hydrazide
premixes.

1. A method for preparing ranitidine phenolic hydrazide premixes, characterized in that it

comprises the following process steps: (1) a phenolic hydrazides ranitidine first crushed
through 800~1000 mesh sieve, and 350 sodium values rot mesh powder mixed with a dry
direct compression granulator into granules, a particle size of 85~100 mesh, ranitidine
mixture ratio by weight of phenol acid hydrazide and sodium humate powder is I:. 0 5~I;
(2) the phenol obtained ranitidine hydrazide and sodium humate composite particles with a
particle size of 85~100 object of the carrier material into the mixer and the amount of the
phenolic hydrazide of ranitidine it should ranitidine in phenolic hydrazide content premix is
5~20% by weight, after stirring uniformly finished in the phenolic hydrazide ranitidine
premixes.
The method for preparing ranitidine phenolic hydrazide premix according to claim I,
wherein said carrier is an organic carrier or an inorganic carrier; wherein the carrier is an
organic beans Bo flour, wheat bran, rice bran, starch, corn flour or corn cobs; wherein the
inorganic carrier is calcium carbonate, shell powder, or zeolite powder.