CN107233342A - A kind of solid dispersions containing TMP and preparation method thereof - Google Patents

A kind of solid dispersions containing TMP and preparation method thereof Download PDF

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Publication number
CN107233342A
CN107233342A CN201710437623.9A CN201710437623A CN107233342A CN 107233342 A CN107233342 A CN 107233342A CN 201710437623 A CN201710437623 A CN 201710437623A CN 107233342 A CN107233342 A CN 107233342A
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tmp
parts
powder
solid dispersions
plant extracts
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魏海涛
方秋华
利光辉
刘初亮
刘铄佳
刘佳华
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Jieyang Embellish Casing Co Ltd
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Jieyang Embellish Casing Co Ltd
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    • A—HUMAN NECESSITIES
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    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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    • A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
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    • A61K31/736—Glucomannans or galactomannans, e.g. locust bean gum, guar gum
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    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/36—Blood coagulation or fibrinolysis factors
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
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    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
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    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds

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Abstract

Disclosed by the invention is a kind of solid dispersions containing TMP and preparation method thereof, belongs to veterinary drug technical field.It is characterized in that by following component proportion, TMP：100~300g；Water-solubility carrier：100~400g；Fibrinolytically active polypeptide：0.5‑5g；High polymer material：10‑30g；Plant extracts powder：5‑20g；Solid phase dispersion auxiliary material：100‑200g；DEXTROSE ANHYDROUS：Add to 1000g；Prepared using comminuting method.TMP solid dispersions prepared by the present invention, can be applied to prepare compound sulfonamide soluble powder, complete water-soluble, solution clear, and livestock and fowl drinking water administration gives full play to TMP and the synergistic function of sulfanilamide salt.

Description

A kind of solid dispersions containing TMP and preparation method thereof
Technical field
The present invention relates to veterinary drug technical field, it is specifically related to a kind of containing the solid dispersions of TMP and its preparation side Method.
Background technology
TMP (Trimethoprim), also known as trimethoprim, Trimethoprim, has a broad antifungal spectrum, to many Planting gram-positive bacteria and negative bacterium has antibacterial action, wherein more sensitive have hemolytic streptococcus, staphylococcus, large intestine bar Bacterium, proteus, Pasteurella and salmonella etc..TMP is alone to be also easy to produce drug resistance, share can strengthen sulfa drug and The curative effect of Multiple Classes of Antibiotics, is referred to as Trimethoprim., can be from two different links simultaneously when TMP is shared with sulfamido Block folic acid metabolism and play double blocking, antibacterial action strengthens several times to hundreds times when sharing, or even becomes bacteriostasis For bactericidal action.
Under large-scale cultivation background, drinking water administration is that a kind of the most frequently used approach is administered in Animal Populations.Drinking water administration letter Just it is, time saving and energy saving, can reduce or avoid livestock and poultry stress.Especially, often there is appetite useless exhausted, it is difficult to pass through in high fever livestock and poultry The oral administrations such as mixed feeding；The physiological requirement drunk yearningly, amount of drinking water increase, therefore drinking water administration, which typically occur, in high fever livestock and poultry to be turned into It is adapted to the optimization approach of high fever livestock and poultry medication.But, TMP is almost insoluble in water, it is impossible to pass through drink with sulfanilamide salt compound Water administering mode is used, and seriously constrains its application in breeding production.TMP has a lactate salt, but lactic acid first The pyridine of oxygen benzyl and sulfanilamide salt compound, occur that soda acid changes when being dissolved in water, separate out muddy, it is impossible to be administered by water way.
Conventional TMP product and and its lactic acid formulation, it is difficult to the water solubility problems shared with sulfanilamide salt are solved, in water In easily precipitate, easily block drinking-water system, cause drug waste, animal absorbs and bioavilability is very low, and easily causes medicine Residual, and the generation of antibody-resistant bacterium is induced, seriously constrain compound sulfonamide class medicine answering in livestock and poultry prevention and treatment With.
Fibrolase is that a kind of peptide activity being made up of 203 amino acid residues (specifically, is a kind of metal Protease), the enzyme is initially by southern copperhead (Southern Copperhead snake) venom purifies and separates； The U.S. Patent No. 4,610,879 (Markland etc.) that September in 1986 is authorized on the 9th；With Guan etc., Archives of Biochemistry and Biophysics, volume 289, the 2nd phase, the 197-207 pages (1991).This enzyme is shown directly FA and it is few or without hemorrhagic activity.It dissolve or the blood clot that is made up of fibrinogen or The blood clot being made up of whole blood.Also it has been determined that fibrolase amino acid sequence, is also related to its yeast recombinant production side Description and its of method treat the application of thrombotic disorders in vivo；Randolph etc., Protein Science, Cambridge University Press (1992), the 590-600 pages, and the European patent announced on July 12nd, 1989 Apply No. 0323722 (Valenzuela etc.).
Fibrinolytically active polypeptide has potential industrial use, uses it for the solid dispersions containing TMP In can improve the overall water solubility of dispersant, be new trial in the disclosure.Although Fibrinolytically active polypeptide for Promote the water-soluble principle of TMP also unintelligible, inventors believe that stomach Fibrinolytically active polypeptide is strong for beasts Health plays a role, and can play certain synergy, and not shadow to the compounding of TMP and other compositions The function that the composition has in itself is rung, the principle is illustrated by more testing.
In order to preferably promote application of the TMP in breeding production, the association of TMP and sulfanilamide salt is given full play to Same synergistic effect, the present invention improves the water solubility of TMP by the preparation process of solid dispersions, finds suitable component Compatibility and appropriate each component ratio, research and produce the simple TMP solid dispersions of technique urgently to be resolved hurrily as this area Technical problem.
The content of the invention
It is an object of the invention to the defect and technical deficiency for overcoming existing TMP product, there is provided a kind of methoxy benzyl Pyridine solid dispersions, hydrophily is extremely strong, and especially water-soluble effect is good under alkaline environment, can pass through drinking-water side with sulfanilamide salt compound Formula is administered, and aqueous solution clarification is not precipitated, and does not block drinking-water system.
Another technical problem to be solved by the present invention is that find suitable component compatibility and appropriate each component ratio there is provided The preparation method of the TMP solid dispersions, simple and easy to apply, cost is relatively low.
It is a still further object of the present invention to provide the TMP solid dispersions answering in compound sulfonamide soluble powder With giving full play to TMP and the synergistic function of sulfanilamide salt.
The technical scheme is that：A kind of solid dispersions containing TMP, by following component proportion：
The sequence amino acid sequence of the Fibrinolytically active polypeptide is as shown in SEQ ID NO.1 in sequence table；
The high polymer material be polyacrylic resin Eudragit L100, polyacrylic resin Eudragit S100, Polycarboxylate by etc. weight than mixing；
The plant extracts powder is by apple powder, astragalus polyose, aloe acetylated mannosan, sesamol, white black false hellebore Alcohol is constituted, by weight component meter, wherein, 5-10 parts of apple powder, 1-1.3 parts of astragalus polyose, aloe acetylated mannosan 0.1- 0.2 part, 0.05-0.1 parts of sesamol, 0.01-0.1 parts of resveratrol.Apple powder, which has, promotes intestinal health, improves the work of taste There is the effect of strengthen immunity volume with, astragalus polyose, aloe acetylated mannosan have enhancing immunocompetence, anti-curing cancers, Healing wounds, anti-disease and radioresistance etc. are acted on, the preferable antioxidation of sesamol part bag postal, and there is resveratrol anti-inflammatory to resist Bacterium lipid-loweringing strengthens immunization.
Further, in such scheme, described water-solubility carrier, including sodium carboxymethylcellulose, dodecyl sulphur Sour sodium, preferably sodium dodecyl sulfate, they can single application, also can use in conjunction.
Further, in such scheme, the solid phase dispersion auxiliary material component meter by weight is comprised the following ingredients：It is many 16-30 parts of permeability superfine silica gel powder, 5-15 parts of alginic acid, 10-20 parts of propylene glycol alginate, 11-15 parts of Explotab, crosslinking carboxylic 5-50 parts of sodium carboxymethylcellulose pyce, 1.8-10 parts of PVP K30,1-2 parts of lauryl sodium sulfate, 0.02-0.2 parts of leucine.
Further, in such scheme, the powder size of the plant extracts powder is 10-100um.
Present invention simultaneously provides the preparation method of the solid dispersions containing TMP, step is as follows：
1) TMP, water soluble carrier material, Fibrinolytically active polypeptide, high score are weighed by the component proportion Sub- material, plant extracts powder, solid phase dispersion auxiliary material, it is standby；
2) by the TMP, water soluble carrier material, high polymer material, plant extracts powder, solid phase dispersion auxiliary material Respectively 10-100um is fully crushed to pulverizer；
3) TMP after crushing and water soluble carrier material powder are all mixed at 60-70 DEG C, and insulation is stirred 10-30min is mixed, mixer rotating speed is 400-800r/min；50-55 DEG C is cooled to, high polymer material, plant after addition crushing Extract powder, solid phase dispersion auxiliary material, insulated and stirred 10-30min, mixer rotating speed is 800-1000r/min；It is cooled to often Temperature, adds Fibrinolytically active polypeptide, and remainder complements to 1000g with DEXTROSE ANHYDROUS, after being sufficiently mixed, 200- 300r/min dispersed with stirring 10-15 minutes, then ball milling, are produced.
Present invention also offers the application of the TMP solid dispersions, by the solid containing TMP point Granular media is applied to prepare compound sulfonamide soluble powder, and solution clear, livestock and fowl drinking water administration gives full play to TMP and sulphur The synergistic function of amine salt.
Compared with prior art, beneficial effects of the present invention be embodied in it is following some：
(1) present invention searches out suitable carrier component compatibility and appropriate each component ratio, successfully prepares one kind TMP solid dispersions, water-soluble effect is good, and each component is nontoxic cheap and easy to get, and preparation method is simple and easy to apply, cost compared with It is low, it is adapted to industrialization production；
(2) TMP solid dispersions, hydrophily is extremely strong, and especially water-soluble effect is good under alkaline environment, can be with sulphur Amine salt compound is administered by water way, and aqueous solution clarification is not precipitated, and does not block drinking-water system, and drug availability is high；
(3) TMP solid dispersions, can be applied to prepare compound sulfonamide soluble powder, it is to avoid use lactic acid methoxy With the acid-base reaction produced by sulfanilamide salt during benzyl pyridine；
(4) TMP solid dispersions are with sulfanilamide salt compound in use, completely water-soluble, and dosage is more accurate, fills TMP and the synergistic function of sulfanilamide salt are waved in distribution.
Embodiment
The present invention is further described with reference to specific embodiment.
Embodiment 1：TMP solid dispersions are prepared, by following component proportion：
Wherein, the sequence amino acid sequence of Fibrinolytically active polypeptide is as shown in SEQ ID NO.1 in sequence table；
The plant extracts powder is by apple powder, astragalus polyose, aloe acetylated mannosan, sesamol, white black false hellebore Alcohol is constituted, and the powder size of plant extracts powder is 10um.Component meter by weight, wherein, 5 parts of apple powder, 1 part of astragalus polyose, 0.1 part of aloe acetylated mannosan, 0.05 part of sesamol, 0.01 part of resveratrol.Apple powder, which has, promotes intestinal health, changes The effect of kind taste, astragalus polyose has an effect of strengthen immunity volume, aloe acetylated mannosan have enhancing immunocompetence, Anti- curing cancers, healing wounds, anti-disease and radioresistance etc. are acted on, the preferable antioxidation of sesamol part bag postal, resveratrol Strengthen immunization with anti-inflammatory, antibacterial lipid-loweringing.
Wherein, water-solubility carrier is sodium carboxymethylcellulose.Solid phase dispersion auxiliary material component meter by weight is by following component Composition：16 parts of porous superfine silica gel powder, 5 parts of alginic acid, 10 parts of propylene glycol alginate, 11 parts of Explotab, cross-linked carboxymethyl 5 parts of sodium cellulosate, 1.8 parts of PVP K30,1 part of lauryl sodium sulfate, 0.02 part of leucine.
Preparation method is as follows：
1) TMP, water soluble carrier material, Fibrinolytically active polypeptide, high score are weighed by the component proportion Sub- material, plant extracts powder, solid phase dispersion auxiliary material, it is standby；
2) by the TMP, water soluble carrier material, high polymer material, plant extracts powder, solid phase dispersion auxiliary material Respectively 10um is fully crushed to pulverizer；
3) TMP after crushing and water soluble carrier material powder are all mixed at 60 DEG C, and insulated and stirred 10min, mixer rotating speed is 400r/min；It is cooled to 50 DEG C, it is the high polymer material that adds after crushing, plant extracts powder, solid Mutually disperse auxiliary material, insulated and stirred 10min, mixer rotating speed is 800r/min；Normal temperature is cooled to, fibrinolysis is added Active peptides, remainder complements to 1000g with DEXTROSE ANHYDROUS, after being sufficiently mixed, 200r/min dispersed with stirring 10 minutes, then Ball milling, is produced.
Embodiment 2：
TMP solid dispersions are prepared, by following component proportion：
Wherein, the sequence amino acid sequence of Fibrinolytically active polypeptide is as shown in SEQ ID NO.1 in sequence table；
The plant extracts powder is by apple powder, astragalus polyose, aloe acetylated mannosan, sesamol, white black false hellebore Alcohol is constituted, and the powder size of plant extracts powder is 55um.Component meter by weight, wherein, 7.5 parts of apple powder, astragalus polyose 1.15 parts, 0.15 part of aloe acetylated mannosan, 0.075 part of sesamol, 0.05 part of resveratrol.Apple powder, which has, promotes intestines Road health, improves the effect of taste, and astragalus polyose has the effect of strengthen immunity volume, and aloe acetylated mannosan has enhancing Immunocompetence, anti-curing cancers, healing wounds, anti-disease and radioresistance etc. are acted on, the preferable antioxidation of sesamol part bag postal, There is resveratrol anti-inflammatory, antibacterial lipid-loweringing to strengthen immunization.
Wherein, water-solubility carrier is lauryl sodium sulfate.Solid phase dispersion auxiliary material component meter by weight is by following component Composition：23 parts of porous superfine silica gel powder, 10 parts of alginic acid, 15 parts of propylene glycol alginate, 13 parts of Explotab, cross-linked carboxymethyl 27.5 parts of sodium cellulosate, 5.9 parts of PVP K30,1.5 parts of lauryl sodium sulfate, 0.11 part of leucine.
Preparation method is as follows：
1) TMP, water soluble carrier material, Fibrinolytically active polypeptide, high score are weighed by the component proportion Sub- material, plant extracts powder, solid phase dispersion auxiliary material, it is standby；
2) by the TMP, water soluble carrier material, high polymer material, plant extracts powder, solid phase dispersion auxiliary material Respectively 55um is fully crushed to pulverizer；
3) TMP after crushing and water soluble carrier material powder are all mixed at 65 DEG C, and insulated and stirred 20min, mixer rotating speed is 600r/min；Be cooled to 52.5 DEG C, the high polymer material that adds after crushing, plant extracts powder, Solid phase dispersion auxiliary material, insulated and stirred 20min, mixer rotating speed is 900r/min；Normal temperature is cooled to, plasmin is added Active peptides are solved, remainder complements to 1000g with DEXTROSE ANHYDROUS, after being sufficiently mixed, 12.5 points of 250r/min dispersed with stirring Clock, then ball milling, are produced.
Embodiment 3：
TMP solid dispersions are prepared, by following component proportion：
Wherein, the sequence amino acid sequence of Fibrinolytically active polypeptide is as shown in SEQ ID NO.1 in sequence table；
The plant extracts powder is by apple powder, astragalus polyose, aloe acetylated mannosan, sesamol, white black false hellebore Alcohol is constituted, and the powder size of plant extracts powder is 100um.Component meter by weight, wherein, 10 parts of apple powder, astragalus polyose 1.3 Part, 0.2 part of aloe acetylated mannosan, 0.1 part of sesamol, 0.1 part of resveratrol.Apple powder, which has, promotes intestinal health, Improve the effect of taste, astragalus polyose has the effect of strengthen immunity volume, and aloe acetylated mannosan has enhancing immunity energy Power, anti-curing cancers, healing wounds, anti-disease and radioresistance etc. are acted on, the preferable antioxidation of sesamol part bag postal, white black false hellebore There is alcohol anti-inflammatory, antibacterial lipid-loweringing to strengthen immunization.
Wherein, water-solubility carrier is by 1 by sodium carboxymethylcellulose and lauryl sodium sulfate:2 weight is than mixing group Into.Solid phase dispersion auxiliary material component meter by weight is comprised the following ingredients：30 parts of porous superfine silica gel powder, 15 parts of alginic acid, algae Sour 20 parts of propylene diester, 15 parts of Explotab, 50 parts of Ac-Di-Sol, 10 parts of PVP K30, dodecyl sulphur Sour 2 parts of sodium, 0.2 part of leucine.
Preparation method is as follows：
1) TMP, water soluble carrier material, Fibrinolytically active polypeptide, high score are weighed by the component proportion Sub- material, plant extracts powder, solid phase dispersion auxiliary material, it is standby；
2) by the TMP, water soluble carrier material, high polymer material, plant extracts powder, solid phase dispersion auxiliary material Respectively 100um is fully crushed to pulverizer；
3) TMP after crushing and water soluble carrier material powder are all mixed at 70 DEG C, and insulated and stirred 30min, mixer rotating speed is 800r/min；It is cooled to 55 DEG C, it is the high polymer material that adds after crushing, plant extracts powder, solid Mutually disperse auxiliary material, insulated and stirred 30min, mixer rotating speed is 1000r/min；Normal temperature is cooled to, plasmin is added Active peptides are solved, remainder complements to 1000g with DEXTROSE ANHYDROUS, after being sufficiently mixed, 300r/min dispersed with stirring 15 minutes, Ball milling, is produced again.
Embodiment 4：TMP solid dispersions prepared by embodiment 1 are applied to prepare compound sulfonamide soluble powder, Formula is as follows：
Prinzone (Squibb)： 100g；
TMP solid dispersions： 66.7g；
DEXTROSE ANHYDROUS： 833.3g.
Preparation method is：Weigh Prinzone (Squibb) by the component proportion, it is 30% TMP solid dispersions, anhydrous Glucose, is uniformly mixed, and crosses 100 mesh sieves and produces.Solution clear, livestock and fowl drinking water administration, gives full play to TMP With the synergistic function of sulfanilamide salt.
Embodiment 5：:TMP solid dispersions prepared by embodiment 2 are applied to prepare compound sulfonamide soluble powder, Formula is as follows：
Prinzone (Squibb)： 200g；
TMP solid dispersions： 133.3g；
DEXTROSE ANHYDROUS： 666.7g.
Preparation method is：Prinzone (Squibb), TMP solid dispersions, anhydrous grape are weighed by the component proportion Sugar, is uniformly mixed, and crosses 100 mesh sieves and produces.Solution clear, livestock and fowl drinking water administration, gives full play to TMP and sulphur The synergistic function of amine salt.
Embodiment 6：TMP solid dispersions prepared by embodiment 3 are applied to prepare compound sulfonamide soluble powder, Formula is as follows：
Prinzone (Squibb)： 150g；
TMP solid dispersions： 166.7g；
DEXTROSE ANHYDROUS： 683.3g.
Preparation method is：Prinzone (Squibb), TMP solid dispersions, anhydrous grape are weighed by the component proportion Sugar, is uniformly mixed, and crosses 100 mesh sieves and produces.Solution clear, livestock and fowl drinking water administration, gives full play to TMP and sulphur The synergistic function of amine salt.
Finally it should be noted that above example be the present invention relatively preferred embodiment, be not intended to limit this The scope of invention, the scope of the present invention is determined with core content according to claims.
Sequence table
<110>Jieyang City's profit reaches casing Co., Ltd
<120>A kind of solid dispersions containing TMP and preparation method thereof
<141> 2017.02.18
<160> 198
<210> 1
<211> 201
<212> PRT
<213>Artificial sequence
<220>
<223>The description of artificial sequence：NAT(AgkistrodonContourtrix fibrolase analog)
<400>1
Ser Phe Pro Gln Arg Tyr Val Gln Leu Val Ile Val Ala Asp His Arg
1 5 10 15
Met Asn Thr Lys Tyr Asn Gly Asp Ser Asp Lys Ile Arg Gln Trp Val
20 25 30
His Gln Ile Val Asn Thr Ile Asn Glu Ile Tyr Arg Pro Leu Asn Ile
35 40 45
Gln Phe Thr Leu Val Gly Leu Glu Ile Trp Ser Asn Gln Asp Leu Ile
50 55 60
Thr Val Thr Ser Val Ser His Asp Thr Leu Ala Ser Phe Gly Asn Trp
65 70 75 80
Arg Glu Thr Asp Leu Leu Arg Arg Gln Arg His Asp Asn Ala Gln Leu
85 90 95
Leu Thr Ala Ile Asp Phe Asp Gly Asp Thr Val Gly Leu Ala Tyr Val
100 105 110
Gly Gly Met Cys Gln Leu Lys His Ser Thr Gly Val Ile Gln Asp His
115 120 125
Ser Ala Ile Asn Leu Leu Val Ala Leu Thr Met Ala His Glu Leu Gly
130 135 140
His Asn Leu Gly Met Asn His Asp Gly Asn Gln Cys His Cys Gly Ala
145 150 155 160
Asn Ser Cys Val Met Ala Ala Met Leu Ser Asp Gln Pro Ser Lys Leu
165 170 175
Phe Ser Asp Cys Ser Lys Lys Asp Tyr Gln Thr Phe Leu Thr Val Asn
180 185 190
Asn Pro Gln Cys Ile Leu Asn Lys Pro
195 200

Claims (6)

1. a kind of solid dispersions containing TMP, it is characterised in that by following component proportion：
The sequence amino acid sequence of the Fibrinolytically active polypeptide is as shown in SEQ ID NO.1 in sequence table；
The high polymer material is polyacrylic resin Eudragit L100, polyacrylic resin Eudragit S100, poly- carboxylic Acid esters by etc. weight than mixing；
The plant extracts powder is by apple powder, astragalus polyose, aloe acetylated mannosan, sesamol, resveratrol group Into, component meter by weight, wherein, 5-10 parts of apple powder, 1-1.3 parts of astragalus polyose, aloe acetylated mannosan 0.1-0.2 Part, 0.05-0.1 parts of sesamol, 0.01-0.1 parts of resveratrol.
2. a kind of solid dispersions containing TMP according to claim 1, it is characterised in that described water-soluble load Body, including sodium carboxymethylcellulose, lauryl sodium sulfate, preferably sodium dodecyl sulfate, they can single application, can also join Close application.
3. a kind of solid dispersions containing TMP according to claim 1, it is characterised in that the solid phase dispersion is auxiliary Material component meter by weight is comprised the following ingredients：16-30 parts of porous superfine silica gel powder, 5-15 parts of alginic acid, propylene glycol alginate 10-20 parts, 11-15 parts of Explotab, 5-50 parts of Ac-Di-Sol, 1.8-10 parts of PVP K30, dodecane 1-2 parts of base sodium sulphate, 0.02-0.2 parts of leucine.
4. a kind of solid dispersions as claimed in claim 1 containing TMP, it is characterised in that the plant extracts powder Powder size be 10-100um.
5. a kind of solid dispersions containing TMP as described in claim 1-4, it is characterised in that preparation method is as follows：
1) TMP, water soluble carrier material, Fibrinolytically active polypeptide, macromolecule material are weighed by the component proportion Material, plant extracts powder, solid phase dispersion auxiliary material, it is standby；
2) TMP, water soluble carrier material, high polymer material, plant extracts powder, solid phase dispersion auxiliary material are distinguished 10-100um is fully crushed to pulverizer；
3) TMP after crushing and water soluble carrier material powder are all mixed at 60-70 DEG C, and insulated and stirred 10- 30min, mixer rotating speed is 400-800r/min；50-55 DEG C is cooled to, high polymer material, plant extract after addition crushing Thing powder, solid phase dispersion auxiliary material, insulated and stirred 10-30min, mixer rotating speed is 800-1000r/min；Normal temperature is cooled to, then Fibrinolytically active polypeptide is added, remainder complements to 1000g with DEXTROSE ANHYDROUS, after being sufficiently mixed, 200-300r/ Min dispersed with stirring 10-15 minutes, then ball milling, are produced.
6. the solid dispersions containing TMP described in a kind of claim 1, it is characterised in that applied to preparing compound sulfonamide Soluble powder, solution clear, livestock and fowl drinking water administration gives full play to TMP and the synergistic function of sulfanilamide salt.
CN201710437623.9A 2017-06-12 2017-06-12 A kind of solid dispersions containing TMP and preparation method thereof Pending CN107233342A (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1674928A (en) * 2002-06-21 2005-09-28 安姆根有限公司 Method for treatment of indwelling catheter occlusion using fibrinolytic metalloproteinases
CN103830184A (en) * 2014-02-18 2014-06-04 北京大学 Solid dispersion system of febuxostat and preparation method of solid dispersion system, and pharmaceutical applications
CN104095928A (en) * 2014-07-28 2014-10-15 山东省动物疫病预防与控制中心 Medicine for treating proteus mirabilis type digestive tract disease
CN106265527A (en) * 2016-11-08 2017-01-04 江西派尼生物药业有限公司 A kind of water soluble trimethoprim compositions and complex composition thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1674928A (en) * 2002-06-21 2005-09-28 安姆根有限公司 Method for treatment of indwelling catheter occlusion using fibrinolytic metalloproteinases
CN103830184A (en) * 2014-02-18 2014-06-04 北京大学 Solid dispersion system of febuxostat and preparation method of solid dispersion system, and pharmaceutical applications
CN104095928A (en) * 2014-07-28 2014-10-15 山东省动物疫病预防与控制中心 Medicine for treating proteus mirabilis type digestive tract disease
CN106265527A (en) * 2016-11-08 2017-01-04 江西派尼生物药业有限公司 A kind of water soluble trimethoprim compositions and complex composition thereof

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