阅读说明：本技术 一种那西肽可溶性粉及其制备方法 (Nosiheptide soluble powder and preparation method thereof ) 是由 马承国 王磊 陆静 夏胜东 于 2018-06-08 设计创作，主要内容包括：本发明提供了一种那西肽可溶性粉及其制备方法,所述西肽可溶性粉,包括：那西肽、载体、助溶剂。所述助溶剂为泊洛沙姆、聚乙烯吡咯烷酮,聚乙二醇、脱氧胆酸钠、聚山梨酯中的一种或几种。本发明中所选用的助溶剂具有优良的生理惰性,又具有优良的生物相容性,使得那西肽可以均匀的溶解在水中,形成澄清均匀的溶液,能够更好被吸收利用,提高生物利用度；所选用的一种或几种载体组分,保证了常温下那西肽可溶性粉具有较大的溶解度,使那西肽在常温条件下的溶解度可达2％。本发明提供的那西肽水溶性粉的制备方法,设备常规,制备工艺简单,适于工业化大生产。(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.)

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.

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.