A kind of parvaquin injection and preparation method thereof

Abstract

The invention belongs to the pharmaceutical field, and specifically relates to a parvaquin injection and a preparation method thereof. The parvaquin injection comprises the following components: a stabilizer, a solubilizer, an antioxidant and a preservative, and the solvent is used to dilute the solution to a fixed volume. By selecting a suitable stabilizer and a solubilizer, and a suitable antioxidant, oxidation of the drug solution during storage is prevented to obtain a clear and stable solution. The preparation method is simple, the process is easy to control, and the solution is suitable for large-scale production. The drug has good solubility and stable quality.

Description

Technical Field

[0001] The invention belongs to the pharmaceutical field, and in particular relates to a parvaquin injection and a preparation method thereof. Background Art

[0002] The chemical name of parvaquinone is 2-cyclohexyl-3-hydroxy-1,4-naphthoquinone. It is a new drug for the treatment of cattle pyrophagoides. Cattle pyrophagoides is a disease in which various pear-shaped parasites of the genus Theileriidae parasitize cattle red blood cells, macrophages and lymphocytes, causing anemia and lymphadenopathy in cattle. It is a seasonal epidemic, mostly acute, with high morbidity and mortality. Parvaquinone injection is a new drug. Currently, there is no relevant formula and preparation method for parvaquinone injection. Summary of the invention

[0003] In order to solve the problems existing in the above-mentioned prior art, the present invention provides a parvaquin injection, comprising the following components: parvaquin, a stabilizer, a solubilizer, an antioxidant and a preservative, which is diluted with a solvent to a fixed volume, and a clear and stable solution with stable quality is obtained by selecting a suitable stabilizer and a solubilizer.

[0004] The present invention also provides a method for preparing parvaquin injection. The specific technical scheme adopted by the present invention is that the preparation method is simple, the process is easy to control, and parvaquin injection with stable quality can be obtained.

[0005] The technical solution adopted by the present invention is: a parvaquin injection, which mainly comprises the following components in parts by weight: 0.5-35 parts of parvaquin, 1-75 parts of stabilizer, 0.01-20 parts of solubilizer, 0.0005-5 parts of antioxidant, 0.01-10 parts of preservative, and is diluted to a fixed volume with 1-90 parts of solvent.

[0006] Preferably, the parvaquinone is 0.5-30 parts; the stabilizer is 1-70 parts; the solubilizer is 0.1-10 parts; the antioxidant is 0.001-2 parts, the preservative is 0.1-5 parts, and the mixture is diluted to a fixed volume with 1-90 parts of solvent.

[0007] Preferably, the stabilizer is one or more of dimethylacetamide, N-methylpyrrolidone and dimethyl sulfoxide.

[0008] Preferably, the solubilizing agent is one or more of Tween 80 and Span 80.

[0009] Preferably, the antioxidant is one or more of butylated hydroxytoluene, butylated hydroxyanisole and propyl gallate.

[0010] Preferably, the preservative is one or more of benzyl alcohol, chlorobutanol and thimerosal.

[0011] Preferably, the solvent is one or more of polyethylene glycol 400, caprylic glyceryl, ethyl oleate, and isopropyl myristate.

[0012] A method for preparing parvaquin injection, which mainly comprises the following steps:

[0013] (A) Take 1-30 parts of stabilizer to dissolve the antioxidant;

[0014] (B) Add the remaining stabilizer and parvaquinone and stir thoroughly until dissolved;

[0015] (C) adding a solubilizing agent and a preservative in sequence and stirring evenly, adding a solvent to make up the volume, filtering, filling, and sterilizing at 100° C. with circulating steam for 30-45 minutes to obtain the parvaquinone injection.

[0016] The invention has the following beneficial effects: parvaquin is almost insoluble in water, and the invention selects suitable stabilizers and solubilizers to enable parvaquin to form a clear and stable solution, and selects suitable antioxidants to prevent the drug solution from being oxidized during storage; in addition, the parvaquin injection provided by the invention has a small amount of organic solvent used, good drug solubility, stable solution, simple preparation method, easy process control, is suitable for large-scale production, and has stable quality. DETAILED DESCRIPTION

[0017] The present invention will be further described below in conjunction with specific embodiments:

[0018] The invention discloses a parvaquin injection, which comprises the following components in parts by weight: 0.5-35 parts of parvaquin, 1-75 parts of a stabilizer, 0.01-20 parts of a solubilizer, 0.0005-5 parts of an antioxidant, 0.01-10 parts of a preservative, and is diluted to a fixed volume with 1-90 parts of a solvent. Example

[0019] (A) Take 5 parts of dimethylacetamide and dissolve 0.2 parts of butylated hydroxytoluene;

[0020] (B) Add the remaining dimethylacetamide and 3 parts of parvaquinone and stir thoroughly until dissolved;

[0021] (C) Add 0.8 parts of Tween 80 and 1 part of benzyl alcohol in sequence and stir evenly, add polyethylene glycol 400 to 100 ml, filter, seal, and sterilize at 100°C circulating steam for 30 minutes to obtain parvaquinone injection. Example

[0022] (A) Dissolve 0.1 part of butylated hydroxyanisole in 10 parts of dimethyl sulfoxide;

[0023] (B) Add the remaining dimethyl sulfoxide and 5 parts of parvaquinone and stir thoroughly until dissolved;

[0024] (C) Add 1 part of Tween 80 and 1 part of chlorobutanol in sequence and stir evenly, add caprylic acid glyceride to 100 ml, filter, seal, and sterilize at 100°C with circulating steam for 45 minutes to obtain parvaquinone injection. Example

[0025] (A) Take 8 parts of N-methylpyrrolidone and dissolve 0.2 parts of propyl gallate;

[0026] (B) Add the remaining N-methylpyrrolidone and 10 parts of parvaquinone, and stir thoroughly until dissolved;

[0027] (C) Add 1.5 parts of Span 80 and 2 parts of benzyl alcohol in sequence and stir evenly, add isopropyl myristate to 100 ml, filter, seal, and sterilize at 100°C with circulating steam for 45 minutes to obtain parvaquinone injection. Example

[0028] (A) Take 20 parts of dimethyl sulfoxide and dissolve 0.15 parts of propyl gallate;

[0029] (B) Add the remaining dimethyl sulfoxide and 15 parts of parvaquinone and stir thoroughly until dissolved;

[0030] (C) Add 1.1 parts of Tween 80 and 2 parts of chlorobutanol in sequence and stir evenly, add ethyl oleate to 100 ml, filter, seal, and sterilize at 100°C with circulating steam for 40 minutes to obtain parvaquinone injection. Example

[0031] (A) Take 10 parts of dimethylacetamide and dissolve 0.02 parts of butylated hydroxyanisole;

[0032] (B) Add the remaining dimethylacetamide and 20 g of parvaquinone and stir thoroughly until dissolved;

[0033] (C) Add 0.9 g of Span 80 and 1.5 g of chlorobutanol in sequence and stir evenly, add propylene glycol to 100 ml, filter, seal, and sterilize at 100°C with circulating steam for 35 minutes to obtain parvaquinone injection. Example

[0034] , add 70 parts of ethyl oleate, 0.02 parts of propyl gallate and 15 parts of parvaquinone and stir evenly;

[0035] , add 1 part of Tween 80 and 1.2 parts of chlorobutanol in sequence and stir evenly, add ethyl oleate to 100 ml, filter, seal, and sterilize at 100°C with circulating steam for 45 minutes to obtain parvaquinone injection. Example

[0036] (A) Dissolve 0.02 parts of butylated hydroxyanisole in 15 parts of dimethyl sulfoxide;

[0037] (B) Add the remaining dimethyl sulfoxide and 10 parts of parvaquinone and stir thoroughly until dissolved;

[0038] (C) Add 0.8 parts of chlorobutanol and stir evenly, add caprylic acid glyceride to 100 ml, filter, seal, and sterilize at 100°C with circulating steam for 45 minutes. Initially, a clear solution is obtained, but floccules are precipitated during the storage process. Example

[0039] (A) Add 35 parts of dimethyl sulfoxide and 10 parts of parvaquinone and stir thoroughly until dissolved;

[0040] (B) Add 0.8 parts of Tween 80 and 0.02 parts of chlorobutanol in turn and stir evenly, add caprylic acid glyceride to 100 ml, filter, seal, and sterilize at 100°C with circulating steam for 45 minutes. Initially, a clear solution is obtained, but the color of the solution deepens during storage.

[0041] In the above examples, examples 1-5 all obtained clear parvaquin injections, but no stabilizer was added in example 6, so the obtained drug solution was suspended, not clear, and did not meet the requirements; no solubilizer was added in example 7, and although a clear parvaquin injection was initially obtained, floccules precipitated during the storage process, which did not meet the requirements; no antioxidant was added in example 8, and although a clear parvaquin injection was initially obtained, the color of the drug solution darkened during the storage process, which did not meet the requirements.

[0042] Test Example 1

[0043] Four batches of clear parvaquin injection were prepared according to Example 2, and stability tests were performed, including influencing factor tests (high temperature, light), accelerated tests (temperature 40±2°C, RH75±5%) for 6 months, and long-term tests (25±2°C, RH60±10%) for 24 months. The test conditions, observation time and inspection items are shown in Table 1. The test results are shown in Tables 2-4:

[0044] Table 1 Contents and investigation items of stability test of parvaquin injection

[0045]

[0046] Table 2 Test results of influencing factors

[0047]

[0048] Table 3 Accelerated test results

[0049]

[0050] Table 4 Long-term test results

[0051]

[0052] As can be seen from Table 2, the various test indicators of the parvaquinone injection prepared in the present invention meet the requirements under the conditions of high temperature of 60° C. and strong light, indicating that the product has good stability under the conditions of high temperature and strong light.

[0053] As can be seen from Tables 3 and 4, the physical and chemical properties of the parvaquinone injection prepared by the present invention are basically stable under accelerated and long-term test conditions, and all test indicators meet the established standards and do not show obvious adverse trends, indicating that the quality of this product is stable and can meet the requirements of long-term storage.

[0054] The parvaquinone injection prepared by the preparation method of the invention has low organic solvent usage, good drug solubility, and good solution stability and can be stored for a long time.

Claims

1. A parvaquin injection, characterized in that: The composition comprises the following components by weight: 0.5-30 parts of parvaquinone, 1-70 parts of stabilizer, 0.1-10 parts of solubilizer, 0.001-2 parts of antioxidant, 0.1-5 parts of preservative, and is diluted to a fixed volume with 1-90 parts of solvent; The stabilizer is one or more of dimethylacetamide, N-methylpyrrolidone and dimethyl sulfoxide; The solubilizing agent is one or two of Tween 80 and Span 80; The antioxidant is one or more of butylated hydroxytoluene, butylated hydroxyanisole and propyl gallate; The solvent is one or more of polyethylene glycol 400, caprylic glyceryl, ethyl oleate, and isopropyl myristate.

2. The parvaquinone injection according to claim 1, characterized in that: The preservative is one or more of benzyl alcohol, chlorobutanol and thimerosal.

3. The method for preparing a parvaquin injection according to claim 1, characterized in that: The following steps are involved: (A), taking 1-30 parts of stabilizer to dissolve the antioxidant; (B), adding the remaining stabilizer and parvaquinone, stirring thoroughly until dissolved; (C) adding a solubilizing agent and a preservative in sequence and stirring evenly, adding a solvent to make up the volume, filtering, filling, and sterilizing at 100° C. with circulating steam for 30-45 minutes to obtain the parvaquinone injection.

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