CN110575532A - Nosiheptide soluble powder and preparation method thereof - Google Patents
Nosiheptide soluble powder and preparation method thereof Download PDFInfo
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- CN110575532A CN110575532A CN201810587592.XA CN201810587592A CN110575532A CN 110575532 A CN110575532 A CN 110575532A CN 201810587592 A CN201810587592 A CN 201810587592A CN 110575532 A CN110575532 A CN 110575532A
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- nosiheptide
- soluble powder
- cosolvent
- poloxamer
- carrier
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- FPTCMHOCGKKRGQ-WYOWUDGCSA-N Multhiomycin Natural products CC=C1NC(=O)[C@@H](NC(=O)c2csc(n2)c3cc(O)c(nc3c4csc(n4)[C@H]5CSC(=O)c6[nH]c7cccc(COC(=O)[C@@H](O)C[C@H](NC(=O)c8csc1n8)c9nc(cs9)C(=O)N5)c7c6C)c%10nc(cs%10)C(=O)N[C@@H](C)C(=O)N)[C@H](C)O FPTCMHOCGKKRGQ-WYOWUDGCSA-N 0.000 title claims abstract description 87
- 101800003864 Nosiheptide Proteins 0.000 title claims abstract description 87
- MQWDKYHFGBWGQZ-JQTJYXGUSA-N nosiheptide Chemical compound N([C@H](C(=O)N\C(C=1SC=C(N=1)C(=O)N[C@@H]1CC(O)C(=O)OCC=2C=CC=C3NC(=C(C3=2)C)C(=O)SC[C@H](NC(=O)C=2N=C1SC=2)C=1SC=C(N=1)C1=N2)=C/C)[C@@H](C)O)C(=O)C(N=3)=CSC=3C1=CC(=O)\C2=C1/NC(C(=O)NC(=C)C(N)=O)=CS1 MQWDKYHFGBWGQZ-JQTJYXGUSA-N 0.000 title claims abstract description 87
- 229950006423 nosiheptide Drugs 0.000 title claims abstract description 87
- 239000000843 powder Substances 0.000 title claims abstract description 56
- 238000002360 preparation method Methods 0.000 title abstract description 19
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims abstract description 30
- 239000006184 cosolvent Substances 0.000 claims abstract description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229920001983 poloxamer Polymers 0.000 claims abstract description 14
- 229960000502 poloxamer Drugs 0.000 claims abstract description 14
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 14
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims abstract description 14
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 14
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 13
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 13
- 229960003964 deoxycholic acid Drugs 0.000 claims abstract description 5
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 claims abstract description 5
- 229920000136 polysorbate Polymers 0.000 claims abstract description 5
- 229950008882 polysorbate Drugs 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims description 27
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims description 19
- 239000003381 stabilizer Substances 0.000 claims description 18
- 239000011259 mixed solution Substances 0.000 claims description 17
- 229920001993 poloxamer 188 Polymers 0.000 claims description 16
- 229940044519 poloxamer 188 Drugs 0.000 claims description 16
- 238000001694 spray drying Methods 0.000 claims description 11
- 239000000463 material Substances 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 239000004552 water soluble powder Substances 0.000 abstract 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 14
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 14
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 7
- 244000269722 Thea sinensis Species 0.000 description 7
- 229930003268 Vitamin C Natural products 0.000 description 7
- 229930003427 Vitamin E Natural products 0.000 description 7
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 7
- 150000008442 polyphenolic compounds Chemical class 0.000 description 7
- 235000013824 polyphenols Nutrition 0.000 description 7
- 235000019154 vitamin C Nutrition 0.000 description 7
- 239000011718 vitamin C Substances 0.000 description 7
- 235000019165 vitamin E Nutrition 0.000 description 7
- 229940046009 vitamin E Drugs 0.000 description 7
- 239000011709 vitamin E Substances 0.000 description 7
- 229920001651 Cyanoacrylate Polymers 0.000 description 6
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 6
- 235000019393 L-cystine Nutrition 0.000 description 6
- 239000004158 L-cystine Substances 0.000 description 6
- 229960003067 cystine Drugs 0.000 description 6
- JJJFUHOGVZWXNQ-UHFFFAOYSA-N enbucrilate Chemical compound CCCCOC(=O)C(=C)C#N JJJFUHOGVZWXNQ-UHFFFAOYSA-N 0.000 description 6
- 229950010048 enbucrilate Drugs 0.000 description 6
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 5
- 239000000243 solution Substances 0.000 description 4
- PWKSKIMOESPYIA-UHFFFAOYSA-N 2-acetamido-3-sulfanylpropanoic acid Chemical compound CC(=O)NC(CS)C(O)=O PWKSKIMOESPYIA-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 235000013616 tea Nutrition 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 239000004626 polylactic acid Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000003910 polypeptide antibiotic agent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000273 veterinary drug Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Communicable Diseases (AREA)
- Organic Chemistry (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Preparation (AREA)
Abstract
the invention provides nosiheptide soluble powder and a preparation method thereof, wherein the nosiheptide soluble powder comprises the following components: nosiheptide, carrier and cosolvent. The cosolvent is one or more of poloxamer, polyvinylpyrrolidone, polyethylene glycol, sodium deoxycholate and polysorbate. The cosolvent selected by the invention has excellent physiological inertia and excellent biocompatibility, so that the nosiheptide can be uniformly dissolved in water to form a clear and uniform solution, can be better absorbed and utilized, and improves the bioavailability; one or more selected carrier components ensure that the nosiheptide soluble powder has higher solubility at normal temperature, so that the solubility of the nosiheptide can reach 2% at normal temperature. The preparation method of the nosiheptide water-soluble powder provided by the invention has the advantages of conventional equipment and simple preparation process, and is suitable for industrial mass production.
Description
Technical Field
the invention relates to a veterinary drug preparation and a preparation method thereof, in particular to nosiheptide soluble powder and a preparation method thereof.
Background
nosiheptide is a sulfur-containing polypeptide antibiotic, is an antibiotic special for animals, has high activity on gram-positive bacteria, and is particularly sensitive to staphylococcus, bacillus subtilis and clostridium welchii. The antibacterial spectrum for gram-negative bacteria is narrow, and compared with the same class of products, the nosiheptide also has very good antiviral effect. The action mechanism of the nosiheptide is mainly to inhibit the synthesis of bacterial protein by inhibiting ribosome, inhibit the growth of harmful bacteria in the intestines, greatly enhance the absorption function of the intestinal canal wall, promote the growth of animals, improve the utilization rate of feed and have wide clinical application.
At present, only two types of formulations, namely nosiheptide premix and granules, are available in the market, and the main problems of the products are that nosiheptide is difficult to be uniformly mixed due to low dosage when being mixed and used, and the non-soluble nosiheptide is difficult to dissolve and absorb in animals, so that the bioavailability is low. Along with the intensification and scale of livestock breeding, the soluble medicine is increasingly widely applied, and the advantages of convenience, timeliness, flexibility, high efficiency and the like of drinking water administration are gradually highlighted. The nosiheptide is hardly dissolved in water, and how to prepare the nosiheptide into soluble powder is a technical problem to be solved urgently.
Disclosure of Invention
In order to solve the technical problems, the invention aims to provide nosiheptide soluble powder and a preparation method thereof.
In one aspect of the invention, a preparation method of nosiheptide soluble powder is provided, each component of the nosiheptide soluble powder composition comprises an auxiliary material and nosiheptide, and the method comprises the following steps:
(1) Dissolving auxiliary materials including a carrier and a cosolvent into water to obtain a mixed solution;
(2) adding nosiheptide into the mixed solution, and dissolving;
(3) and (5) spray drying.
Preferably, the adjuvant further comprises a stabilizer.
Preferably, in the nosiheptide soluble powder composition, the mass ratio of the nosiheptide is 0.5% -5%.
In a preferred embodiment, the carrier may be one or a combination of several of hydroxypropyl-beta-cyclodextrin, polylactic-co-glycolic acid (PLGA), polylactic acid (PLA), polylactide-caprolactone (PACA), poly n-Butyl Cyanoacrylate (BCA), polyethylene glycol (PEG), and polyamide-amine (PAMAM).
In a preferred embodiment, in the nosiheptide soluble powder composition, the mass proportion of the carrier is 50% -90%, preferably 60% -80%.
In a preferred embodiment, the carrier comprises hydroxypropyl-beta-cyclodextrin and polyamide-amine, and preferably, in the nosiheptide soluble powder composition, the mass ratio of the hydroxypropyl-beta-cyclodextrin is 30% -45%, and the mass ratio of the polyamide-amine is 30% -45%.
Preferably, the mass ratio of the hydroxypropyl-beta-cyclodextrin to the polyamide-amine in the carrier is (05-2) to (0.8-1.5), preferably 1 (0.8-1.5), and more preferably 1 (1-1.2).
Preferably, the cosolvent can be one or more of poloxamer, polyvinylpyrrolidone (PVP), polyethylene glycol, sodium deoxycholate and polysorbate; more preferably, the co-solvent may be PVPK 30; more preferably, the co-solvent may be poloxamer 188.
In a preferred embodiment, in the nosiheptide soluble powder composition, the cosolvent accounts for 10-40% by mass, and is more preferably 12-35% by mass.
In a preferred embodiment, the co-solvent comprises: poloxamer 188 and PVPK 30; more preferably, in the nosiheptide soluble powder composition, the mass ratio of the poloxamer 188 is 12% -20%, and the mass ratio of the PVPK30 is 12% -20%.
Preferably, the mass ratio of the poloxamer 188 to the PVPK30 is (05-2): (0.8-1.5), preferably 1: (0.8-1.5), more preferably 1: (1-1.2).
Preferably, the stabilizer can be one or more of vitamin C, vitamin E, L-cystine, L-cysteine, and tea polyphenol.
Preferably, in the nosiheptide soluble powder composition, the mass proportion of the stabilizer is not higher than 5%, and more preferably 0.5% -2%.
In a preferred embodiment, the viscosity of the mixed solution is 10-1000mm2S, preferably 20 to 500mm2/s。
preferably, after weighing each component of the auxiliary materials, the components can be respectively dissolved in water and then mixed, or the components can be mixed first and then dissolved in water.
In a preferred embodiment, the spray drying condition is that the inlet air temperature is 120-160 ℃; more preferably the inlet air temperature is 130-.
in a preferred embodiment, the spray drying conditions are an outlet air temperature of 40 ℃ to 90 ℃; more preferably, the temperature of the air outlet is 50-65 ℃.
in a preferred embodiment, the feed rate of the spray drying step is 5-50ml/min, more preferably 10-20 ml/min.
In another aspect of the present invention, there is provided a nosiheptide soluble powder comprising: nosiheptide, carrier and cosolvent.
Preferably, in the nosiheptide soluble powder composition, the mass ratio of the nosiheptide is 0.5% -5%.
In a preferred embodiment, the carrier may be one or a combination of hydroxypropyl- β -cyclodextrin, poly (lactic-co-glycolic acid) (PLGA), poly (lactic acid) (PLA), poly (lactide-co-glycolide) (PACA), poly (n-Butyl Cyanoacrylate) (BCA), polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polyamide-amine (PAMAM).
In a preferred embodiment, in the nosiheptide soluble powder composition, the mass proportion of the carrier is 50% -90%, preferably 60% -80%.
In a preferred embodiment, the carrier comprises hydroxypropyl-beta-cyclodextrin and polyamide-amine, and preferably, in the nosiheptide soluble powder composition, the mass ratio of the hydroxypropyl-beta-cyclodextrin is 30% -45%, and the mass ratio of the polyamide-amine is 30% -45%.
preferably, the mass ratio of the hydroxypropyl-beta-cyclodextrin to the polyamide-amine in the carrier is (05-2) to (0.8-1.5), preferably 1 (0.8-1.5), and more preferably 1 (1-1.2).
preferably, the cosolvent can be one or more of poloxamer, polyvinylpyrrolidone (PVP), polyethylene glycol, sodium deoxycholate and polysorbate; more preferably, the PVP may be PVPK 30; more preferably, the poloxamer may be poloxamer 188.
in a preferred embodiment, the cosolvent is 10-40% by mass, more preferably 12-35% by mass, of the nosiheptide soluble powder composition.
In a preferred embodiment, the co-solvent comprises: poloxamer 188 and PVPK 30; more preferably, in the nosiheptide soluble powder composition, the mass ratio of the poloxamer 188 is 12% -20%, and the mass ratio of the PVPK30 is 12% -20%.
Preferably, in the nosiheptide soluble powder composition, the mass ratio of the poloxamer 188 to the PVPK30 is (05-2) to (0.8-1.5), preferably 1 (0.8-1.5), and more preferably 1 (1-1.2).
In a preferred embodiment, the nosiheptide soluble powder composition further comprises a stabilizer.
Preferably, the stabilizer can be one or more of vitamin C, vitamin E, L-cystine, L-cysteine, and tea polyphenol.
Preferably, in the nosiheptide soluble powder composition, the mass proportion of the stabilizer is not higher than 5%, and more preferably 0.5% -2%.
In a preferred embodiment, the nosiheptide soluble powder composition comprises, by mass, 0.5% -2.0% of nosiheptide, 35% -45% of hydroxypropyl-beta-cyclodextrin, 18812% -20% of poloxamer, 3012% -20% of PVPK, 35% -45% of polyamide-amine and 0.5% -2% of a stabilizer.
in the above context of the present invention, a range of values may be given as one or more fixed values or ranges of values selected from the range.
The nosiheptide soluble powder and the preparation method thereof provided by the invention have the following beneficial effects:
(1) the cosolvent adopted by the invention has excellent physiological inertia and excellent biocompatibility, so that the nosiheptide can be uniformly dissolved in water to form a clear and uniform solution, can be better absorbed and utilized, and improves the bioavailability.
(2) The invention contains one or more carrier components, and ensures that the nosiheptide soluble powder has higher solubility at normal temperature.
(3) Under the condition of containing the stabilizer, the stability of the nosiheptide soluble powder is improved, the product is easier to store, and the production, circulation and use of the product are more convenient.
(4) The preparation method of the nosiheptide soluble powder provided by the invention has the advantages of conventional equipment and simple preparation process, and is suitable for industrial mass production.
Detailed Description
the nosiheptide soluble powder provided by the invention comprises a carrier, a cosolvent and/or a stabilizer, wherein the carrier can be one or a combination of several of hydroxypropyl-beta-cyclodextrin, polylactic acid-glycolic acid copolymer (PLGA), polylactic acid (PLA), polylactide-caprolactone (PACA), poly (n-Butyl Cyanoacrylate) (BCA),. polyvinylpyrrolidone (PVP), polyethylene glycol (PEG) and polyamide-amine (PAMAM). The cosolvent can be one or more of poloxamer, polyvinylpyrrolidone (PVP), polyethylene glycol, sodium deoxycholate and polysorbate. The stabilizer can be one or more of vitamin C, vitamin E, L-cystine, L-cysteine, and tea polyphenols.
Example 1
The carrier is hydroxypropyl-beta-cyclodextrin and polyamide-amine, the cosolvent is poloxamer 188 and PVPK30, and the stabilizer is vitamin E.
The preparation method of the nosiheptide soluble powder comprises the following steps:
(1) Taking 34.5 parts of hydroxypropyl-beta-cyclodextrin, 18815.0 parts of poloxamer and 3015.0 parts of PVPK, weighing 34.5 parts of polyamide-amine and 1.0 part of vitamin E, and dissolving in water to obtain a mixed solution.
(2) Adding 0.5 part of nosiheptide into the mixed solution, and dissolving;
(3) And (5) spray drying.
The nosiheptide soluble powder obtained in the example has a solubility of 2.2% in water at normal temperature.
Example 2
The carrier is hydroxypropyl-beta-cyclodextrin, the cosolvent is poloxamer 188 and PVPK30, and the stabilizer is vitamin E and L-cystine.
The preparation method of the nosiheptide soluble powder comprises the following steps:
(1) Taking 69 parts of hydroxypropyl-beta-cyclodextrin, 18810.0 parts of poloxamer, 3020.0 parts of PVPK and 1.0 part of vitamin E, and dissolving the mixture in water to obtain a mixed solution.
(2) Adding 1.0 part of nosiheptide into the mixed solution, and dissolving;
(3) And (5) spray drying.
The nosiheptide soluble powder obtained in the example has a solubility of 2% in water at room temperature.
Example 3
The carrier is hydroxypropyl-beta-cyclodextrin and polyamide-amine, the cosolvent is poloxamer 188 and PVPK30, and the stabilizer is vitamin C and L-cystine.
The preparation method of the nosiheptide soluble powder comprises the following steps:
(1) Taking 40 parts of hydroxypropyl-beta-cyclodextrin, 28 parts of polyamide-amine, 18817 parts of poloxamer, 3013 parts of PVPK, 1.0 part of vitamin C and 1.0 part of L-cystine, and dissolving the solution in water to obtain a mixed solution.
(2) Adding 1.5 parts of nosiheptide into the mixed solution, and dissolving;
(3) And (5) spray drying.
the nosiheptide soluble powder obtained in the example has a solubility of 2.1% in water at normal temperature.
Example 4
The carrier is polylactic acid-glycolic acid copolymer and polyamide-amine, the cosolvent is poloxamer 188 and PVPK30, and the stabilizer is tea polyphenol.
The preparation method of the nosiheptide soluble powder comprises the following steps:
Step 1
(1) Taking 20 parts of polylactic acid-glycolic acid copolymer, 49 parts of polyamide-amine, 18815 parts of poloxamer, 3015 parts of PVPK and 1.0 part of tea polyphenol, and dissolving the mixture in water to obtain a mixed solution.
(2) adding 2.0 parts of nosiheptide into the mixed solution, and dissolving;
(3) And (5) spray drying. The nosiheptide soluble powder obtained in the example has a solubility of 2% in water at room temperature.
Example 5
The carrier is selected from polyethylene glycol and polyamide-amine, the cosolvent is selected from poloxamer 188 and PVPK30, and the stabilizer is selected from tea polyphenol.
The preparation method of the nosiheptide soluble powder comprises the following steps:
(1) Taking 25 parts of polyethylene glycol, 44 parts of polyamide-amine, 18820 parts of poloxamer, 3010 parts of PVPK and 1.0 part of tea polyphenol, and dissolving the mixture in water to obtain a mixed solution.
(2) Adding 2.0 parts of nosiheptide into the mixed solution, and dissolving;
(3) And (5) spray drying. The nosiheptide soluble powder obtained in the example has a solubility of 2.1% in water at normal temperature.
Example 6
The carrier is hydroxypropyl-beta-cyclodextrin and polyamide-amine, the cosolvent is poloxamer 188 and PVPK30, and the stabilizer is vitamin C.
the preparation method of the nosiheptide soluble powder comprises the following steps:
(1) taking 40 parts of hydroxypropyl-beta-cyclodextrin, 28 parts of polyamide-amine, 18815 parts of poloxamer, 3015 parts of PVPK and 2 parts of vitamin C, and dissolving the solution in water to obtain a mixed solution.
(2) Adding 2.0 parts of nosiheptide into the mixed solution, and dissolving;
(3) And (5) spray drying. The nosiheptide soluble powder obtained in the example has a solubility of 1.9% in water at normal temperature.
The nosiheptide soluble powder obtained by the invention is tested and evaluated in appearance by adopting the following method:
Weighing a certain amount of nosiheptide soluble powder, putting 100ml of water into a 500ml beaker, putting the product obtained in the six embodiments at room temperature, putting the product into a water bath shaking table, shaking for 30min, observing the dissolution condition, and testing the solubility.
The test results were as follows:
TABLE 1 evaluation and examination results of the solubility and appearance of the solution of nosiheptide obtained in examples 1 to 6
As can be seen from Table 1, the nosiheptide soluble powder has good water-soluble effect, the solubility of the nosiheptide in water can reach more than 2 percent, and the requirement of drinking water administration can be met.
The embodiments of the present invention have been described in detail, but the embodiments are merely examples, and the present invention is not limited to the embodiments described above. Any equivalent modifications and substitutions to those skilled in the art are also within the scope of the present invention. Accordingly, equivalent changes and modifications made without departing from the spirit and scope of the present invention should be covered by the present invention.
Claims (10)
1. A nosiheptide soluble powder, which is a composition comprising: nosiheptide, carrier and cosolvent.
2. The nosiheptide soluble powder as claimed in claim 1, characterized in that the nosiheptide is present in the composition in a mass proportion of 0.5% to 5%.
3. The nosiheptide soluble powder as claimed in claim 1, characterized in that the mass proportion of the cosolvent in the composition is 10% -40%.
4. The nosiheptide soluble powder as claimed in claim 1, characterized in that the cosolvent is one or more selected from poloxamer, polyvinylpyrrolidone (PVP), polyethylene glycol, sodium deoxycholate and polysorbate.
5. A nosiheptide soluble powder as claimed in claim 1 or 4, characterised in that the cosolvent comprises poloxamer 188 and PVPK 30.
6. The nosiheptide soluble powder as claimed in claim 5, characterized in that the mass ratio of the poloxamer 188 to the PVPK30 is (05-2) to (0.8-1.5).
7. The nosiheptide soluble powder as claimed in claim 1, characterised in that the carrier is present in the composition in a proportion by mass of 50% to 90%.
8. A nosiheptide soluble powder as claimed in claim 1, characterised in that the composition comprises a stabilising agent.
9. the nosiheptide soluble powder as claimed in claim 8, characterized in that the composition comprises, by mass, 0.5% -2.0% of nosiheptide, 35% -45% of hydroxypropyl-beta-cyclodextrin, 18812% -20% of poloxamer, 3012% -20% of PVPK, 35% -45% of polyamide-amine and 0.5% -2% of stabilizer.
10. A method of preparing the nosiheptide soluble powder of claim 1, wherein the components of the composition comprise, excipients, and nosiheptide, the method comprising:
(1) Dissolving auxiliary materials including a carrier and a cosolvent into water to obtain a mixed solution;
(2) adding nosiheptide into the mixed solution, and dissolving;
(3) and (5) spray drying.
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| CN112353774A (en) * | 2020-11-17 | 2021-02-12 | 浙江汇能生物股份有限公司 | Nascitide flavor chewable tablet, preparation method thereof and application thereof to clostridium welchii disease of dog |
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