White oil for poultry vaccine injection as well as preparation method and application of white oil

Abstract

The invention relates to the field of vaccine oil, and relates to white oil for poultry vaccine injection as well as a preparation method and application thereof. The preparation method comprises the following steps: 1, taking atmospheric and vacuum distillate oil of intermediate base crude oil and / or paraffin base crude oil as raw material oil, and contacting the raw material oil with an extraction agent for extraction treatment to obtain low aromatic oil; 2, hydrotreating the low aromatic hydrocarbon oil by using a hydrotreating catalyst to obtain hydrotreated generated oil; 3, carrying out hydrodewaxing treatment on the hydrotreated generated oil by adopting a hydrodewaxing catalyst to obtain hydrodewaxed generated oil; 4, performing primary hydrofining on the hydrodewaxing generated oil by adopting a primary hydrofining catalyst to obtain primary hydrofining generated oil; 5, carrying out secondary hydrofining on the primary hydrofining generated oil by adopting a secondary hydrofining catalyst to obtain secondary hydrofining generated oil; and 6, carrying out precise fractionation on the secondary hydrofining generated oil to obtain the white oil for poultry vaccine injection. The white oil antibody has excellent titer and is especially suitable for preparing highly pathogenic virus vaccines.

Description

Technical Field

[0001] This invention relates to the field of vaccine oil technology, specifically to a white oil for poultry vaccine injection, its preparation method, and its application. Background Technology

[0002] White oil for poultry vaccines, also known as vaccine white oil, is a crucial substance in vaccine production. Its high purity, sterility, simple composition, and good biocompatibility make it essential for enhancing vaccine efficacy. It significantly strengthens the immune response by activating the immune system and boosting the immune response to antigens in the vaccine.

[0003] The main technical indicators for white oil used in poultry vaccine injections are absorption performance and antibody efficacy. Currently, white oil used in poultry vaccine injections still suffers from low antibody titers.

[0004] CN201511014680.3 discloses a white oil specifically for low-pour-point inactivated vaccine adjuvants. The white oil is composed of hydrocarbon compounds with 15-26 carbon atoms, with an alkanes content of 80-90% (w / w) and a n-alkanes content of 5-10% (w / w). This white oil for inactivated vaccine adjuvants can meet the requirements for use of low-pour-point inactivated vaccines at low temperatures. However, the antibody titer of this white oil for inactivated vaccine adjuvants still needs further improvement.

[0005] CN201711453972.6 discloses a method for preparing and applying a highly efficient, low-toxicity food-grade white oil for poultry vaccines, which involves adding C to the food-grade white oil. 16 -C 20 By thoroughly mixing n-alkane monomers, a highly efficient and low-toxicity food-grade white oil for poultry vaccines can be obtained. However, this method, which stimulates poultry to produce more antibodies and improves vaccine potency by adding chemically synthesized single-structure saturated hydrocarbons, is expensive and unsuitable for industrial production. Summary of the Invention

[0006] The purpose of this invention is to solve the problem that while the absorption performance of white oil used in poultry vaccines, especially white oil used in highly pathogenic virus vaccines, meets the requirements of the vaccine, the antibody titer is relatively poor. This invention provides a white oil for poultry vaccines, its preparation method, and its application.

[0007] To achieve the above objectives, a first aspect of the present invention provides a method for preparing white oil for poultry vaccine injection, wherein the method includes the following steps:

[0008] (1) Using atmospheric and vacuum distillate oil of intermediate base crude oil and / or paraffinic base crude oil as feed oil, the feed oil is contacted with an extractant for extraction treatment to obtain low aromatic oil;

[0009] (2) The low-aromatic oil is hydrogenated using a hydrogenation catalyst to obtain hydrogenated oil;

[0010] (3) The hydrotreated oil is subjected to hydrodewaxing treatment using a hydrodewaxing catalyst to obtain hydrodewaxing oil.

[0011] (4) The hydrodepressed oil is subjected to primary hydrorefining using a primary hydrorefining catalyst to obtain primary hydrorefined oil;

[0012] (5) The primary hydrorefining product oil is subjected to secondary hydrorefining using a secondary hydrorefining catalyst to obtain a secondary hydrorefining product oil;

[0013] (6) The oil produced by the secondary hydrorefining is subjected to precision fractionation to obtain white oil for poultry vaccine injection with a distillation range of 310-365℃.

[0014] A second aspect of the present invention provides a white oil for injecting poultry vaccines, wherein the carbon number distribution of the white oil for injecting poultry vaccines is 14-21;

[0015] Based on the total mass of the white oil, the white oil contains 70-85 wt% total alkanes, 15-30 wt% total cycloalkanes, and ≤0.01 wt% total aromatics.

[0016] Based on the total mass of the white oil, the content of the n-alkanes is 5-10 wt%, and the content of the monobranched isoalkanes is ≥35 wt%.

[0017] A third aspect of the present invention provides the application of the white oil for avian vaccine injection described in the second aspect of the present invention in a highly pathogenic virus vaccine.

[0018] The beneficial technical effects achieved by the present invention through the above technical solution are as follows:

[0019] 1) The preparation method of white oil for poultry vaccine injection provided in this invention involves sequentially extracting, hydrogenating, hydrodewaxing, first-stage hydrogenating, second-stage hydrogenating, and precision fractionation of the raw oil. This method can deeply remove sulfur, nitrogen, and oxygen compounds and aromatics from the raw oil. It can not only effectively control the carbon number distribution and the content of alkanes and cycloalkanes in the white oil, but also adjust the content of n-alkanes and monobranched isoalkanes in the white oil. As a result, it can obtain white oil for poultry vaccine injection that is basically free of aromatics, has absorption performance that meets the basic requirements for vaccine use, and has excellent or extremely excellent antibody titers. It is particularly suitable for use in highly pathogenic virus vaccines.

[0020] 2) The preparation method of the white oil for poultry vaccine injection provided in this invention produces a white oil for poultry vaccine injection that is odorless, tasteless, and free of aromatics. It has excellent color stability, light and heat stability, oxidation stability, and antioxidant stability. It can be stored for a long time, and its shelf life is not less than 1 year under the storage environment of food-grade white oil.

[0021] 3) The preparation method of white oil for poultry vaccine injection provided in this invention has a simple process, mild operating conditions, and low production cost, making it suitable for industrial promotion. Attached Figure Description

[0022] Figure 1-5 The graphs show the carbon number distribution test results of the white oil for poultry vaccine injection prepared in Examples 1-4 and Comparative Example 1, respectively. Detailed Implementation

[0023] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0024] A first aspect of the present invention provides a method for preparing white oil for poultry vaccine injection, wherein the method includes the following steps:

[0025] (1) Using atmospheric and vacuum distillate oil of intermediate base crude oil and / or paraffinic base crude oil as feed oil, the feed oil is contacted with an extractant for extraction treatment to obtain low aromatic oil;

[0026] (2) The low-aromatic oil is hydrogenated using a hydrogenation catalyst to obtain hydrogenated oil;

[0027] (3) The hydrotreated oil is subjected to hydrodewaxing treatment using a hydrodewaxing catalyst to obtain hydrodewaxing oil.

[0028] (4) The hydrodepressed oil is subjected to primary hydrorefining using a primary hydrorefining catalyst to obtain primary hydrorefined oil;

[0029] (5) The primary hydrorefining product oil is subjected to secondary hydrorefining using a secondary hydrorefining catalyst to obtain a secondary hydrorefining product oil;

[0030] (6) The oil produced by the secondary hydrorefining is subjected to precision fractionation to obtain white oil for poultry vaccine injection with a distillation range of 310℃-365℃.

[0031] In this invention, the inventors discovered through research that the content of n-alkanes and monobranched isoalkanes has a significant impact on the high antibody titer of white oil for poultry vaccine injection. By sequentially subjecting the raw oil to extraction, hydrogenation, hydrodewaxing, primary hydrogenation refining, secondary hydrogenation refining, and precision fractionation, not only can the carbon number distribution and the content of alkanes and cycloalkanes in the white oil for poultry vaccine injection be effectively controlled, but the content of n-alkanes and monobranched isoalkanes in the white oil can also be adjusted. This results in poultry vaccine white oil with excellent or even extremely excellent antibody titers (i.e., a maximum antibody titer index greater than or equal to 11.5, or even greater than or equal to 12.0, within 180 days of immunization), absorption performance meeting the basic requirements for vaccine use (i.e., a safety rating between B and A-), and excellent stability and antioxidant stability. The poultry vaccine white oil of this invention is particularly suitable for preparing vaccines against highly pathogenic viruses.

[0032] In step (1):

[0033] In a preferred embodiment of the present invention, the distillation range of the intermediate-based crude oil atmospheric and vacuum distillate is 280-420℃, preferably 320-380℃; the distillation range of the paraffinic crude oil atmospheric and vacuum distillate is 280-420℃, preferably 300-360℃. The terms "intermediate-based crude oil," "paraffinic crude oil," and "atmospheric and vacuum distillate" in this invention have well-known meanings and will not be elaborated upon further.

[0034] In a preferred embodiment of the present invention, the feedstock oil meets the requirements for feedstocks in a high-pressure hydrogenation process (approximately 10-25 MPa). Specifically, the feedstock oil has a total metal content of less than 2.0 μg / g, a heptane-insoluble content of less than 0.02 wt%, a salt content of less than 1.0 mg / L, a water content of less than 300 μg / g, an iron content of less than 1.5 μg / g, and a residual carbon content of less than 1 wt%. To ensure that the feedstock oil meets the requirements for feedstocks in the high-pressure hydrogenation process, it can be pre-purified by hydrogenation according to methods known in the art before extraction.

[0035] In a preferred embodiment of the present invention, the extractant is selected from one or more of furfural, N-methylpyrrolidone, phenol, dimethyl sulfoxide and sulfolane, preferably furfural.

[0036] In this invention, the main components of the feedstock oil are alkanes, cycloalkanes, aromatics, and polar compounds including gums and asphaltenes. Compared with hydrocracking to remove aromatics, extraction can separate most of the aromatics and polar compounds from the feedstock oil without causing the loss of alkanes, especially n-alkanes, thus helping to maintain the content of alkanes, n-alkanes, and monobranched isoalkanes in the prepared white oil for poultry vaccine injection.

[0037] In a preferred embodiment of the present invention, the operating conditions for the extraction process include: a mass ratio of extraction solvent to feed oil of 0.5-5:1, preferably 1-3:1; an extraction temperature of 40-120℃, preferably 60-100℃; and an extraction time of 5-40 min, preferably 10-20 min. Furthermore, in this invention, low-aromatic oil can be obtained by separation after extraction.

[0038] In a preferred embodiment of the present invention, the extraction process is centrifugal extraction, preferably multi-stage centrifugal extraction. The operating conditions for multi-stage centrifugal extraction include: 10-20 extraction stages, centrifugal speed of 2000-4000 rpm, feed oil temperature of 40-80℃, extraction temperature of 60-100℃, extraction solvent to feed oil mass ratio of 1-3:1, and contact time per stage of 10-20 min.

[0039] In step (2):

[0040] In a preferred embodiment of the present invention, the hydrotreating is used to remove impurities such as sulfur, nitrogen, oxygen, and metals from the low-aromatic oil, and to catalyze the saturated hydrogenation reaction of aromatics and the ring-opening reaction of cycloalkanes. The present invention does not impose any particular limitation on the catalyst used for hydrotreating; any hydrotreating catalyst capable of performing the above-mentioned functions can be used in the present invention. For example, based on the total mass of the hydrotreating catalyst, the hydrotreating catalyst comprises 55-80 wt%, preferably 60-70 wt%, of alumina, 20-40 wt%, preferably 25-35 wt%, of tungsten oxide and / or nickel oxide, and 0-5 wt%, preferably 2-4 wt%, of phosphorus pentoxide.

[0041] In a preferred embodiment of the present invention, the hydrogenation catalyst is first pre-sulfurized, and then subjected to hydrogenation treatment; wherein the operating conditions for the hydrogenation treatment include: a hydrogen partial pressure of 10-25 MPa, preferably 12-22 MPa, more preferably 20-22 MPa; a reaction temperature of 330-430°C, preferably 350-410°C, more preferably 350-370°C; and a volume hourly space velocity of 0.1-2 h⁻¹. -1 Preferably, it is 0.2-1.5h. -1Further preferably 0.8-1.2h -1 The hydrogen-to-oil volume ratio is 500-3500:1, preferably 1000-3000:1, and more preferably 1400-1600:1.

[0042] In this invention, unless otherwise specified, volume hourly space velocity refers to the mass ratio of oil feed rate to catalyst stock. Hydrogenation treatment of low-aromatic oil helps optimize the component content in white oil for poultry vaccine injection, further improving the oil stability and extending the shelf life of the white oil for poultry vaccine injection.

[0043] In step (3):

[0044] In a preferred embodiment of the present invention, hydrodewaxing is used to crack large-molecule n-alkanes in hydrotreated product oil into smaller-molecule n-alkanes. The present invention does not specifically limit the hydrodewaxing catalyst; any hydrodewaxing catalyst known in the art can be used in the present invention. For example, based on the total mass of the hydrodewaxing catalyst, the hydrodewaxing catalyst may include 92-99.5 wt%, preferably 95-98 wt%, of molecular sieve, 0.5-5.5 wt%, preferably 3-4 wt%, of nickel oxide, and 0-0.15 wt%, preferably 0.05-0.1 wt%, of copper oxide.

[0045] In a preferred embodiment of the present invention, the hydrodewaxing catalyst is first pre-sulfurized, and then subjected to hydrodewaxing treatment; wherein the operating conditions for hydrodewaxing include: a hydrogen partial pressure of 10-25 MPa, preferably 12-22 MPa, more preferably 20-22 MPa; a reaction temperature of 180-300°C, preferably 200-280°C, more preferably 200-220°C; and a volume hourly space velocity of 0.1-2.5 h⁻¹. -1 Preferably 0.3-2h -1 More preferably 0.3-0.6h -1 The hydrogen-to-oil volume ratio is 300-3500:1, preferably 500-3000:1, and more preferably 1500-2000:1.

[0046] In this invention, compared with isomerization dewaxing, hydrodewaxing treatment can retain the content of n-alkanes and monobranched isoalkanes in the product as much as possible. This not only helps to improve the antibody titer of white oil for poultry vaccine injection, but also reduces the freezing point of the white oil product, improves the low-temperature performance of the product, and increases the safe absorption performance of white oil for poultry vaccine injection.

[0047] In step (4):

[0048] In a preferred embodiment of the present invention, the primary hydrorefining is used to eliminate unsaturated bonds and non-hydrocarbon compounds in the hydrodewaxing product. Hydrorefining catalysts known in the art can be used in this invention. For example, based on the total mass of the primary hydrorefining catalyst, the primary hydrorefining catalyst comprises 85-97 wt%, preferably 87-95 wt%, of alumina; 3-15 wt%, preferably 6.5-9.5 wt%, of molybdenum oxide; and 0.2-2.5 wt%, preferably 0.8-1.5 wt%, of nickel oxide.

[0049] In a preferred embodiment of the present invention, the primary hydrorefining catalyst is first pre-sulfurized, and then subjected to a primary hydrorefining treatment; wherein the operating conditions for the primary hydrorefining include: a hydrogen partial pressure of 10-25 MPa, preferably 12-22 MPa, more preferably 20-22 MPa; a reaction temperature of 160-320°C, preferably 180-300°C, more preferably 280-300°C; and a volume hourly space velocity of 0.5-3.5 h⁻¹. -1 Preferably 1-3h -1 More preferably 1.5-2.5h -1 The hydrogen-to-oil volume ratio is 300-3500:1, preferably 500-3000:1, and more preferably 2000-2500:1.

[0050] In this invention, the hydrorefining of the dewaxing oil can further eliminate unsaturated bonds in the dewaxing oil, which helps to extend the storage time of white oil for poultry vaccine injection.

[0051] In a preferred embodiment of the present invention, the pre-sulfurization of the hydrotreating catalyst, the hydrodewaxing catalyst, and the primary hydrorefining catalyst is not particularly limited, and methods known in the art can be used for pre-sulfurization. The pre-sulfurization operations of the hydrotreating catalyst, the hydrodewaxing catalyst, and the primary hydrorefining catalyst can be the same or different. For example, using 95-97 wt% kerosene and 3-5 wt% dimethyl disulfide as the sulfiding oil, at a hydrogen partial pressure of 6-7 MPa and a volume hourly space velocity of 0.5-1.5 h⁻¹. -1 Under the condition of a hydrogen-to-oil volume ratio of 500-700:1, the temperature is first raised to 200-250℃ at a heating rate of 5-10℃ / h, and pre-sulfurized for 4-8h. Then the temperature is raised to 290-320℃ and pre-sulfurized for another 4-8h.

[0052] In step (5):

[0053] In a preferred embodiment of the present invention, the secondary hydrorefining is used for deep hydrorefining to deeply saturate the unsaturated hydrocarbons in the primary hydrorefining product oil and further remove trace amounts of non-hydrocarbon compounds. Deep hydrorefining catalysts known in the art can be used in this invention. For example, based on the total mass of the secondary hydrorefining catalyst, the secondary hydrorefining catalyst comprises 94-99.5 wt%, preferably 97.5-99 wt%, of alumina, 0.5-2.5 wt%, preferably 1-2 wt%, of platinum oxide and / or palladium oxide, and 0-0.5 wt%, preferably 0.1-0.2 wt%, of molybdenum oxide.

[0054] In a preferred embodiment of the present invention, the operating conditions for the secondary hydrogenation purification include: a hydrogen partial pressure of 10-25 MPa, preferably 12-22 MPa, more preferably 20-22 MPa; a reaction temperature of 160-320°C, preferably 180-300°C, more preferably 180-220°C; and a volume hourly space velocity of 0.1-2.5 h⁻¹. -1 Preferably 0.3-2h -1 More preferably 0.3-0.8h -1 The hydrogen-to-oil volume ratio is 300-3500:1, preferably 500-3000:1, and more preferably 1500-2000:1.

[0055] In this invention, the oil produced by primary hydrorefining undergoes secondary hydrorefining, which removes trace amounts of sulfur and nitrogen from the primary hydrorefining oil and further reduces the content of unstable functional groups such as unsaturated hydrocarbons, hydroxyl groups, aldehyde groups, and ketone groups in the primary hydrorefining oil. This improves the oxidative stability and photothermal stability of the white oil for poultry vaccine injection, ensuring that the prepared white oil for poultry vaccine injection has a shelf life of not less than one year under food-grade white oil storage conditions without the addition of antioxidants or stabilizers.

[0056] In step (6):

[0057] In a preferred embodiment of the present invention, the distillation range of the white oil for poultry vaccine injection is 320-345°C.

[0058] This invention does not impose specific limitations on the exact operating conditions of precision fractionation, as long as the distillate oil with a distillation range of 310-365℃, preferably 320-345℃, can be separated from the oil produced by secondary hydrorefining. In this invention, the distillate oil with a distillation range of 310-365℃ corresponds to the fraction with 14-21 carbon atoms, and the distillate oil with a distillation range of 320-345℃ corresponds to the fraction with 15-19 carbon atoms. By precisely controlling the carbon number of the white oil for poultry vaccine injection, higher antibody levels can be stimulated in poultry, enabling the white oil for poultry vaccine injection to meet the absorption performance requirements of poultry vaccine oil used for highly pathogenic virus vaccines while also exhibiting higher antibody potency.

[0059] A second aspect of the present invention provides a white oil for injecting poultry vaccines, wherein the carbon number distribution of the white oil for injecting poultry vaccines is 14-21, preferably 15-19;

[0060] Based on the total mass of the white oil, the white oil contains 70-85 wt% total alkanes, preferably 74-76 wt%; 15-30 wt% total cycloalkanes, preferably 24-26 wt%; and ≤0.01 wt% total aromatics, preferably ≤0.0005 wt%.

[0061] Based on the total mass of the white oil, the content of the n-alkanes is 5-10 wt%, preferably 6-7 wt%; the content of the monobranched isoalkanes is ≥35 wt%, preferably 35-43 wt%, and more preferably 36-38 wt%.

[0062] In this invention, the inventors discovered through research that, after adjusting the carbon number distribution, alkanes and cycloalkanes content of the white oil, further adjusting the content of n-alkanes and monobranched isoalkanes in the white oil can enable the white oil for poultry vaccine injection to meet the basic requirements for absorption performance of white oil used in highly pathogenic virus vaccines, while also having a higher and better antibody titer.

[0063] In addition, the white oil for poultry vaccine injection prepared in this invention also has excellent color stability, light and heat stability, oxidation stability and antioxidant stability, and can be stored for a long time. Under the storage environment of food-grade white oil, the shelf life of the white oil for poultry vaccine injection is not less than 1 year.

[0064] In a preferred embodiment of the present invention, the kinematic viscosity (40°C) of the white oil for poultry vaccine injection is 4.4-5.1 mm. 2 / s, density d 20 800-815 kg / m 3The heavy metal content is less than 10 μg / g, the lead content is less than 1 μg / g, the arsenic content is less than 1 μg / g, easily carbonized substances pass, solid paraffin passes, the acidity is neutral, the total aromatic hydrocarbon content in the hydrocarbon composition (ASTM D2786, 3239) is 0, the ultraviolet absorbance (260nm-350nm) is less than 0.01, and the pour point is -26℃ to -18℃.

[0065] In a preferred embodiment of the invention, C is calculated based on the total mass of the white oil. 14 Content not more than 2wt%, C 15 The content is not greater than 5 wt%. In this invention, C is controlled... 14 and C 15 The content of [specific ingredient] helps to further improve the safety performance of white oil for poultry vaccine injection.

[0066] In a preferred embodiment of the present invention, the white oil for poultry vaccine injection is prepared using the preparation method described in the first aspect of the present invention.

[0067] A third aspect of the present invention provides the application of the white oil for avian vaccine injection described in the second aspect of the present invention in a highly pathogenic virus vaccine.

[0068] The highly pathogenic virus in this invention can be a highly pathogenic avian influenza virus, such as H5N1 or H7N9, which can cause serious disease and high mortality after infecting poultry.

[0069] The present invention will be described in detail below through embodiments.

[0070] Feedstock A: Atmospheric and vacuum distillate of paraffin-based crude oil with a boiling range of 280-420℃. Feedstock B: Atmospheric and vacuum distillate of intermediate-based crude oil with a boiling range of 320-380℃. Feedstock A and Feedstock B have been pretreated to meet the feedstock requirements of the high-pressure hydrotreating process: total metal content less than 2.0 μg / g, n-heptane insoluble content less than 0.02 wt%, salt content less than 1.0 mg / L, water content less than 300 μg / g, iron content less than 1.5 μg / g, and residual carbon less than 1 wt%. The properties of Feedstock A and Feedstock B are shown in Table 1.

[0071] Table 1

[0072]

[0073]

[0074] The composition and performance parameters of the hydrotreating catalyst, the hydrodewaxing catalyst, the primary hydrorefining catalyst, and the secondary hydrorefining catalyst are shown in Table 2.

[0075] Table 2

[0076]

[0077] Example 1

[0078] (1) Raw material oil A and sulfolane were simultaneously added to a multi-stage annular gap centrifuge for extraction to obtain low aromatic oil; wherein, the number of extraction stages was 20, the centrifugation speed was 4000 rpm, the feed temperature of raw material oil A was 80℃, the extraction temperature was 100℃, the mass ratio of sulfolane to raw material oil A was 1:1, and the contact time of each stage was 10 min;

[0079] (2) Using 96.7 wt% kerosene and 3.3 wt% dimethyl disulfide as sulfiding oil, at a hydrogen partial pressure of 7.0 MPa and a volume hourly space velocity of 1.0 h⁻¹, the mixture was subjected to a hydrogen hourly space velocity of 1.0 h⁻¹. -1 The hydrotreating catalyst was pre-sulfurized at a hydrogen-to-oil volume ratio of 600:1. The temperature was first increased to 230°C at a rate of 10°C / h for 6 hours of pre-sulfurization, followed by increasing the temperature to 320°C and continuing pre-sulfurization for another 6 hours. Then, the aforementioned low-aromatic oil was introduced for hydrotreating to obtain the hydrotreated product oil. The hydrotreating operating conditions included a hydrogen partial pressure of 14.0 MPa, a reaction temperature of 380°C, and a volume hourly space velocity (VHSV) of 0.6 h⁻¹. -1 The hydrogen-to-oil volume ratio is 1000:1;

[0080] (3) Using 96.7 wt% kerosene and 3.3 wt% dimethyl disulfide as sulfiding oil, at a hydrogen partial pressure of 6.0 MPa and a volume hourly space velocity of 1.0 h⁻¹, the mixture was subjected to a hydrogen flow rate of 1 h⁻¹. -1 The hydrodewaxing catalyst was pre-sulfurized at a hydrogen-to-oil volume ratio of 600:1. The temperature was first increased to 230°C at a rate of 5°C / h and pre-sulfurized for 6 hours. Then, the temperature was increased to 290°C and pre-sulfurized for another 6 hours. The resulting hydrodewaxing oil was then introduced for hydrodewaxing treatment to obtain the hydrodewaxing product oil. The operating conditions for hydrodewaxing included a hydrogen partial pressure of 14.0 MPa, a reaction temperature of 280°C, and a volume hourly space velocity (VHSV) of 1.0 h⁻¹. -1 The hydrogen-to-oil volume ratio is 3000:1;

[0081] (4) Using 96.7 wt% kerosene and 3.3 wt% dimethyl disulfide as sulfiding oil, at a hydrogen partial pressure of 6.0 MPa and a volume hourly space velocity of 1.0 h⁻¹, the mixture was subjected to a hydrogen flow rate of 1 h⁻¹. -1The primary hydrorefining catalyst was pre-sulfurized under a hydrogen-to-oil volume ratio of 600:1. The temperature was first increased to 230°C at a rate of 5°C / h for 6 hours of pre-sulfurization, followed by increasing the temperature to 290°C and continuing pre-sulfurization for another 6 hours. Then, the aforementioned hydrodewaxing product was introduced for primary hydrorefining to obtain the primary hydrorefined product oil. The operating conditions for primary hydrorefining included a hydrogen partial pressure of 14.0 MPa, a reaction temperature of 300°C, and a volume hourly space velocity (VHSV) of 1.5 h⁻¹. -1 The hydrogen-to-oil volume ratio is 3000:1;

[0082] (5) The above-mentioned primary hydrorefining product oil is subjected to secondary hydrorefining using a secondary hydrorefining catalyst to obtain a secondary hydrorefined product oil; wherein the operating conditions for secondary hydrorefining include: hydrogen partial pressure of 14.0 MPa, reaction temperature of 180℃, and volume hourly space velocity of 2.0 h⁻¹. -1 The hydrogen-to-oil volume ratio is 3000:1;

[0083] (6) The above-mentioned secondary hydrogenation refining oil is subjected to precision fractionation to obtain white oil for poultry vaccine injection with a distillation range of 320-345℃.

[0084] Example 2

[0085] (1) Raw material oil A and phenol were simultaneously added to a multi-stage annular gap centrifuge for extraction to obtain low aromatic oil; wherein, the number of extraction stages was 15, the centrifugation speed was 2000 rpm, the feed temperature of raw material oil A was 60℃, the extraction temperature was 80℃, the mass ratio of phenol to raw material oil A was 1.5:1, and the contact time of each stage was 20 min.

[0086] (2) Using 96.7 wt% kerosene and 3.3 wt% dimethyl disulfide as sulfiding oil, at a hydrogen partial pressure of 7.0 MPa and a volume hourly space velocity of 1.0 h⁻¹, the mixture was subjected to a hydrogen hourly space velocity of 1.0 h⁻¹. -1 The hydrotreating catalyst was pre-sulfurized under a hydrogen-to-oil volume ratio of 600:1. The temperature was first increased to 230°C at a rate of 10°C / h for 6 hours of pre-sulfurization, followed by increasing the temperature to 320°C and continuing pre-sulfurization for another 6 hours. Then, the aforementioned low-aromatic oil was introduced for hydrotreating to obtain the hydrotreated product oil. The hydrotreating operating conditions included a hydrogen partial pressure of 18.0 MPa, a reaction temperature of 350°C, and a volume hourly space velocity (VHSV) of 0.2 h⁻¹. -1 The hydrogen-to-oil volume ratio is 2000:1;

[0087] (3) Using 96.7 wt% kerosene and 3.3 wt% dimethyl disulfide as sulfiding oil, at a hydrogen partial pressure of 6.0 MPa and a volume hourly space velocity of 1.0 h⁻¹, the mixture was subjected to a hydrogen flow rate of 1 h⁻¹. -1The hydrodewaxing catalyst was pre-sulfurized at a hydrogen-to-oil volume ratio of 600:1. The temperature was first increased to 230°C at a rate of 5°C / h and pre-sulfurized for 6 hours. Then, the temperature was increased to 290°C and pre-sulfurized for another 6 hours. The resulting hydrodewaxing oil was then introduced into the hydrotreated oil for hydrodewaxing treatment, yielding the hydrodewaxing product oil. The operating conditions for hydrodewaxing included a hydrogen partial pressure of 18.0 MPa, a reaction temperature of 240°C, and a volume hourly space velocity (VHSV) of 0.3 h⁻¹. -1 The hydrogen-to-oil volume ratio is 500:1;

[0088] (4) Using 96.7 wt% kerosene and 3.3 wt% dimethyl disulfide as sulfiding oil, at a hydrogen partial pressure of 6.0 MPa and a volume hourly space velocity of 1.0 h⁻¹, the mixture was subjected to a hydrogen flow rate of 1 h⁻¹. -1 The primary hydrorefining catalyst was pre-sulfurized under a hydrogen-to-oil volume ratio of 600:1. The temperature was first increased to 230°C at a rate of 5°C / h and pre-sulfurized for 6 hours. Then, the temperature was increased to 290°C and pre-sulfurized for another 6 hours. The resulting hydrorefining product was then introduced into the pre-hydrorefined oil to obtain the primary hydrorefined product oil. The operating conditions for primary hydrorefining included a hydrogen partial pressure of 18.0 MPa, a reaction temperature of 250°C, and a volume hourly space velocity (VHSV) of 1.0 h⁻¹. -1 The hydrogen-to-oil volume ratio is 500:1;

[0089] (5) The above-mentioned primary hydrorefining product oil is subjected to secondary hydrorefining using a secondary hydrorefining catalyst to obtain a secondary hydrorefined product oil; wherein the operating conditions for secondary hydrorefining include: hydrogen partial pressure of 18.0 MPa, reaction temperature of 240℃, and volume hourly space velocity of 1.0 h⁻¹. -1 The hydrogen-to-oil volume ratio is 1800:1;

[0090] (6) The above-mentioned secondary hydrogenation refining oil is subjected to precision fractionation to obtain white oil for poultry vaccine injection with a distillation range of 320-345℃.

[0091] Example 3

[0092] (1) Raw material oil B and dimethyl sulfoxide were simultaneously added to a multi-stage annular gap centrifuge for extraction to obtain low aromatic oil; wherein, the number of extraction stages was 10, the centrifugation speed was 2500 rpm, the feed temperature of raw material oil B was 80℃, the extraction temperature was 100℃, the mass ratio of dimethyl sulfoxide to raw material oil B was 3:1, and the contact time of each stage was 15 min;

[0093] (2) Using 96.7 wt% kerosene and 3.3 wt% dimethyl disulfide as sulfiding oil, at a hydrogen partial pressure of 7.0 MPa and a volume hourly space velocity of 1.0 h⁻¹, the mixture was subjected to a hydrogen hourly space velocity of 1.0 h⁻¹. -1The hydrotreating catalyst was pre-sulfurized at a hydrogen-to-oil volume ratio of 600:1. The temperature was first increased to 230°C at a rate of 10°C / h for 6 hours of pre-sulfurization, followed by increasing the temperature to 320°C and continuing pre-sulfurization for another 6 hours. Then, the aforementioned low-aromatic oil was introduced for hydrotreating to obtain the hydrotreated product oil. The operating conditions for hydrotreating included a hydrogen partial pressure of 12.0 MPa, a reaction temperature of 410°C, and a volume hourly space velocity (VHSV) of 1.5 h⁻¹. -1 The hydrogen-to-oil volume ratio is 3000:1;

[0094] (3) Using 96.7 wt% kerosene and 3.3 wt% dimethyl disulfide as sulfiding oil, at a hydrogen partial pressure of 6.0 MPa and a volume hourly space velocity of 1.0 h⁻¹, the mixture was subjected to a hydrogen flow rate of 1 h⁻¹. -1 The hydrodewaxing catalyst was pre-sulfurized at a hydrogen-to-oil volume ratio of 600:1. The temperature was first increased to 230°C at a rate of 5°C / h and pre-sulfurized for 6 hours. Then, the temperature was increased to 290°C and pre-sulfurized for another 6 hours. The resulting hydrodewaxing oil was then introduced for hydrodewaxing treatment to obtain the hydrodewaxing product oil. The operating conditions for hydrodewaxing included a hydrogen partial pressure of 12.0 MPa, a reaction temperature of 280°C, and a volume hourly space velocity (VHSV) of 2.0 h⁻¹. -1 The hydrogen-to-oil volume ratio is 1500:1;

[0095] (4) Using 96.7 wt% kerosene and 3.3 wt% dimethyl disulfide as sulfiding oil, at a hydrogen partial pressure of 6.0 MPa and a volume hourly space velocity of 1.0 h⁻¹, the mixture was subjected to a hydrogen flow rate of 1 h⁻¹. -1 The primary hydrorefining catalyst was pre-sulfurized under a hydrogen-to-oil volume ratio of 600:1. The temperature was first increased to 230°C at a rate of 5°C / h and pre-sulfurized for 6 hours. Then, the temperature was increased to 290°C and pre-sulfurized for another 6 hours. The resulting hydrorefining product was then introduced into the pre-hydrorefined oil to obtain the primary hydrorefined product oil. The operating conditions for primary hydrorefining included a hydrogen partial pressure of 12.0 MPa, a reaction temperature of 180°C, and a volume hourly space velocity (VHSV) of 3.0 h⁻¹. -1 The hydrogen-to-oil volume ratio is 1500:1;

[0096] (5) The primary hydrorefining product oil is subjected to secondary hydrorefining using a secondary hydrorefining catalyst to obtain a secondary hydrorefined product oil; wherein the operating conditions for secondary hydrorefining include: hydrogen partial pressure of 12.0 MPa, reaction temperature of 300 °C, and volume hourly space velocity of 1.5 h⁻¹. -1 The hydrogen-to-oil volume ratio is 500:1;

[0097] (6) The above-mentioned secondary hydrogenation refining oil is subjected to precision fractionation to obtain white oil for poultry vaccine injection with a distillation range of 320-345℃.

[0098] Example 4

[0099] (1) Raw material oil B and furfural were simultaneously added to a multi-stage annular gap centrifuge for extraction treatment. After the two phases were separated, low aromatic oil was obtained. The extraction stage was 18 stages, the centrifugation speed was 3000 rpm, the feed temperature of raw material oil B was 40℃, and the extraction temperature was 60℃. The mass ratio of furfural to raw material oil B was 2.5:1, and the contact time of each stage was 20 min.

[0100] (2) Using 96.7 wt% kerosene and 3.3 wt% dimethyl disulfide as sulfiding oil, at a hydrogen partial pressure of 7.0 MPa and a volume hourly space velocity of 1.0 h⁻¹, the mixture was subjected to a hydrogen hourly space velocity of 1.0 h⁻¹. -1 The hydrotreating catalyst was pre-sulfurized at a hydrogen-to-oil volume ratio of 600:1. The temperature was first increased to 230°C at a rate of 10°C / h for 6 hours of pre-sulfurization, followed by increasing the temperature to 320°C and continuing pre-sulfurization for another 6 hours. Then, the aforementioned low-aromatic oil was introduced for hydrotreating to obtain the hydrotreated product oil. The operating conditions for hydrotreating included a hydrogen partial pressure of 22.0 MPa, a reaction temperature of 350°C, and a volume hourly space velocity (VHSV) of 0.8 h⁻¹. -1 The hydrogen-to-oil volume ratio is 1500:1;

[0101] (3) Using 96.7 wt% kerosene and 3.3 wt% dimethyl disulfide as sulfiding oil, at a hydrogen partial pressure of 6.0 MPa and a volume hourly space velocity of 1.0 h⁻¹, the mixture was subjected to a hydrogen flow rate of 1 h⁻¹. -1 The hydrodewaxing catalyst was pre-sulfurized at a hydrogen-to-oil volume ratio of 600:1. The temperature was first increased to 230°C at a rate of 5°C / h and pre-sulfurized for 6 hours. Then, the temperature was increased to 290°C and pre-sulfurized for another 6 hours. The resulting hydrodewaxing oil was then introduced for hydrodewaxing treatment to obtain the hydrodewaxing product oil. The operating conditions for hydrodewaxing included a hydrogen partial pressure of 22.0 MPa, a reaction temperature of 200°C, and a volume hourly space velocity (VHSV) of 0.3 h⁻¹. -1 The hydrogen-to-oil volume ratio is 2000:1;

[0102] (4) Using 96.7 wt% kerosene and 3.3 wt% dimethyl disulfide as sulfiding oil, at a hydrogen partial pressure of 6.0 MPa and a volume hourly space velocity of 1.0 h⁻¹, the mixture was subjected to a hydrogen flow rate of 1 h⁻¹. -1 The primary hydrorefining catalyst was pre-sulfurized under a hydrogen-to-oil volume ratio of 600:1. The temperature was first increased to 230°C at a rate of 5°C / h for 6 hours of pre-sulfurization, followed by increasing the temperature to 290°C and continuing pre-sulfurization for another 6 hours. Then, the aforementioned hydrodewaxing product oil was introduced for primary hydrorefining to obtain the primary hydrorefined product oil. The operating conditions for primary hydrorefining included a hydrogen partial pressure of 22.0 MPa, a reaction temperature of 300°C, and a volume hourly space velocity (VHSV) of 2.0 h⁻¹. -1 The hydrogen-to-oil volume ratio is 2000:1;

[0103] (5) The primary hydrorefining product oil is subjected to secondary hydrorefining using a secondary hydrorefining catalyst to obtain a secondary hydrorefined product oil; wherein the operating conditions for secondary hydrorefining include: hydrogen partial pressure of 22.0 MPa, reaction temperature of 180 °C, and volume hourly space velocity of 0.3 h⁻¹. -1 The hydrogen-to-oil volume ratio is 1500:1;

[0104] (6) The above-mentioned secondary hydrogenation refining oil is subjected to precision fractionation to obtain white oil for poultry vaccine injection with a distillation range of 320-345℃.

[0105] Comparative Example 1

[0106] Similar to Example 2, except that steps (1) and (3) are different.

[0107] (1) Using 96.7 wt% kerosene and 3.3 wt% dimethyl disulfide as sulfiding oil, commercially available hydrocracking catalyst FC52 was pre-sulfurized under the conditions of hydrogen partial pressure of 7.0 MPa, volume hourly space velocity of 1.0 h-1, and hydrogen-to-oil volume ratio of 600:1. The temperature was first raised to 230 °C at a heating rate of 10 °C / h and pre-sulfurized for 6 h. Then the temperature was raised to 320 °C and pre-sulfurized for another 6 h. Then feedstock A was introduced for hydrocracking reaction to obtain hydrocracking product oil. The operating conditions for hydrocracking included: hydrogen partial pressure of 18.0 MPa, reaction temperature of 400 °C, volume hourly space velocity of 0.3 h-1, and hydrogen-to-oil volume ratio of 2000:1.

[0108] (2) Using 96.7 wt% kerosene and 3.3 wt% dimethyl disulfide as sulfiding oil, the hydrotreating catalyst was pre-sulfurized under the conditions of a hydrogen partial pressure of 7.0 MPa, a volume hourly space velocity (VHSV) of 1.0 h⁻¹, and a hydrogen-to-oil volume ratio of 600:1. The temperature was first increased to 230 °C at a rate of 10 °C / h for 6 h of pre-sulfurization, followed by increasing the temperature to 320 °C and continuing pre-sulfurization for another 6 h. Then, the above-mentioned hydrocracking product oil was introduced for hydrotreating to obtain the hydrotreated product oil. The operating conditions for hydrotreating included a hydrogen partial pressure of 18.0 MPa, a reaction temperature of 350 °C, and a VHSV of 0.2 h⁻¹. -1 The hydrogen-to-oil volume ratio is 2000:1;

[0109] (3) The above-mentioned hydrotreated oil was subjected to isomerization dewaxing using commercially available isomerization dewaxing catalyst FIW-12 to obtain isomerization dewaxing product oil; wherein, the isomerization dewaxing operation conditions include: hydrogen partial pressure of 18.0 MPa, reaction temperature of 340℃, volume hourly space velocity of 0.3 h-1, and hydrogen-to-oil volume ratio of 500:1.

[0110] (4) Using 96.7 wt% kerosene and 3.3 wt% dimethyl disulfide as sulfiding oil, at a hydrogen partial pressure of 6.0 MPa and a volume hourly space velocity of 1.0 h⁻¹, the mixture was subjected to a hydrogen flow rate of 1 h⁻¹.-1 The primary hydrorefining catalyst was pre-sulfurized under a hydrogen-to-oil volume ratio of 600:1. The temperature was first increased to 230°C at a rate of 5°C / h and pre-sulfurized for 6 hours. Then, the temperature was increased to 290°C and pre-sulfurized for another 6 hours. The resulting hydrorefining product was then introduced into the pre-hydrorefined oil to obtain the primary hydrorefined product oil. The operating conditions for primary hydrorefining included a hydrogen partial pressure of 18.0 MPa, a reaction temperature of 250°C, and a volume hourly space velocity (VHSV) of 1.0 h⁻¹. -1 The hydrogen-to-oil volume ratio is 500:1;

[0111] (5) The above-mentioned primary hydrorefining product oil is subjected to secondary hydrorefining using a secondary hydrorefining catalyst to obtain a secondary hydrorefined product oil; wherein the operating conditions for secondary hydrorefining include: hydrogen partial pressure of 18.0 MPa, reaction temperature of 240℃, and volume hourly space velocity of 1.0 h⁻¹. -1 The hydrogen-to-oil volume ratio is 1800:1;

[0112] (6) The above-mentioned secondary hydrogenation refining oil is subjected to precision fractionation to obtain white oil for poultry vaccine injection with a distillation range of 320-385℃.

[0113] Test Example 1

[0114] The carbon number distribution of the white oil for avian vaccine injection prepared in Examples 1-4 and Comparative Example 1 was characterized using the simulated distillation method NBSH / T 0558. The results are as follows: Figure 1-5 As shown.

[0115] Among them, by Figure 1-5 It can be seen that the carbon number of the white oil for poultry vaccine injection prepared in Examples 1-4 is between 15 and 19. 15 The content is not greater than 5 wt%. The white oil for avian vaccine injection prepared in Comparative Example 1 has a carbon number between 15 and 26. 15 Content not exceeding 5 wt%.

[0116] Test Example 2

[0117] The properties of the white oil for avian vaccine injection prepared in Examples 1-4 and Comparative Example 1 were analyzed, and the results are shown in Table 3. Kinematic viscosity (40°C) was tested using ASTM D445, and density d... 20 The tests were conducted according to SH / T0604, the tests for easily carbonized materials were conducted according to ASTM D11079, the tests for UV absorbance were conducted according to ASTM D11081, and the tests for pour point were conducted according to ASTM D97.

[0118] Table 3

[0119]

[0120]

[0121] Note: "ASTM D2786" represents the American Society for Testing and Materials standard ASTM D2786-91 (1996) "Determination of hydrocarbons in saturated hydrocarbon fractions of gas oils (mass spectrometry)"; "ASTM D3239" represents ASTM D3239-91 "Standard test method for the analysis of aromatic types of oil and gas aromatic fractions by high ionization voltage mass spectrometry". Methods for testing n-alkanes and monobranched isoalkanes: GC-FI TOF MS was used to distinguish alkanes with the same number of carbon atoms into polysubstituted isoalkanes, monobranched isoalkanes (i.e., monosubstituted isoalkanes), and n-alkanes with different degrees of isomerism. The content of n-alkanes and monobranched isoalkanes was measured in Jiang Jingjie, Liu Yingrong, Liu Zelong, and Tian Songbai, "Research Report on Chemical Analysis (FENXI HUAXUE); March 2016, Vol. 44, No. 3, pp. 416-422".

[0122] The test results of Test Example 1 and Test Example 2 show that the white oil for poultry vaccine injection obtained by the preparation methods of Examples 1-4 of this invention has a specific distillation range, a carbon number distribution between 15 and 19, and a kinematic viscosity (40°C) of 4.4-5.1 mm. 2 / s, density d 20 800-815 kg / m 3 The heavy metal content is less than 10 μg / g, the lead content is less than 1 μg / g, the arsenic content is less than 1 μg / g, the ultraviolet absorbance (260nm-350nm) is less than 0.1, easily carbonized substances pass through, solid paraffin passes through, the acidity is neutral, the total aromatic hydrocarbon content is 0, the total alkanes content is between 70-85 wt%, the total cycloalkanes content is between 15-30 wt%, the n-alkanes content is between 5-10 wt%, the monobranched isoalkanes are ≥35%, and the shelf life is not less than 1 year under the storage conditions of food-grade white oil.

[0123] Test Example 3

[0124] The white oil for avian vaccine injection prepared in Examples 1-4 and Comparative Example 1 were used to prepare highly pathogenic H7N9 avian influenza oil emulsion inactivated vaccines, and immunization tests were conducted on chickens. Blood samples were collected from all chickens before grouping, and avian influenza hemagglutination inhibition (HI) antibody tests were performed for immunization experiments.

[0125] Absorption performance test:

[0126] One hundred and eighty eligible 28-day-old SPF chickens were randomly divided into six groups of 30 each. All six groups were vaccinated with the aforementioned avian influenza oil-emulsion inactivated vaccine, with each chicken receiving a subcutaneous injection of 0.5 mL in the neck. At 30, 45, 60, 75, and 90 days post-vaccination, five chickens from each group were culled for vaccine residue absorption testing. The results are shown in Table 4.

[0127] Table 4

[0128]

[0129] Note: (-), (+), and (++) represent drug residue test results. (-) indicates no drug residue and no inflammatory reaction; (+) indicates trace drug residue, consisting of a small number of pinhead-sized, milky-white granules, and an inflammatory reaction; (++) indicates a larger amount of drug residue, consisting of millet-grain-sized milky-white granules and 1-2 granulomas the size of mung beans, and an inflammatory reaction.

[0130] Safety Rating: Five chickens culled 90 days after vaccination underwent a drug residue absorption test. If all five chickens had negative drug residue test results, the safety rating was A. If the results were a mix of negative and positive, the safety rating was A- if more negative results were positive than positive, B if more positive results were positive, and C if at least one chicken had positive (++) drug residue test results. The safety rating for vaccine white oil is divided into A, A-, B, and C, with the safety level decreasing progressively. A safety rating of A indicates excellent absorption performance, A- indicates good absorption performance, B indicates acceptable absorption performance, and C indicates unacceptable absorption performance. For white oil used in highly pathogenic virus vaccines, the basic requirement for absorption performance is between B and A-.

[0131] As shown in Table 4, after 90 days, in Examples 1-2, three chickens showed no inflammatory reaction, good absorption, and no residue. Two chickens showed a confirmed inflammatory reaction. Upon dissection of the chickens with inflammatory reactions, a small amount of pinhead-shaped, milky-white particles were observed in the muscle tissue at the injection site. The safety rating was A-. In Examples 3-4, one chicken showed no inflammatory reaction, good absorption, and no residue. Four chickens showed a confirmed inflammatory reaction. Upon dissection of the chickens with inflammatory reactions, a small amount of pinhead-shaped, milky-white particles were observed in the muscle tissue at the injection site. The safety rating was B. In Comparative Example 1, all five chickens showed no inflammatory reaction, good absorption, and no residue. The safety rating was A. Therefore, the white oil for poultry vaccine injection in Examples 1-4 and Comparative Example 1 meets the basic requirements for absorption performance of white oil for highly pathogenic virus vaccines.

[0132] Antibody titer performance test:

[0133] Seventy-two eligible 28-day-old SPF chickens were randomly divided into six groups of 12 each. Five groups were treated with the five avian influenza oil emulsion inactivated vaccines mentioned above, while the remaining group served as a control group and received saline injections. The injection site and dosage were in accordance with the instructions for use of the commercial vaccines, i.e., 0.5 mL was injected subcutaneously into the neck of each chicken.

[0134] At 24, 48, 72, and 120 hours after injection, there were no significant changes in body temperature, feed intake, or mental state in all 28-day-old SPF chickens before and after injection.

[0135] Blood samples were collected from each group at 7, 14, 21, and 30 days post-immunization, and thereafter every two weeks. Ten birds were randomly selected each time to collect blood samples to detect avian influenza serum antibody levels. The results are shown in Table 4. Among these, antibody levels were higher than the minimum antibody titer for immunization protection (≥2). 4 When the animal produces effective immune protection, the serum is isolated and stored at -20°C.

[0136] Table 5

[0137]

[0138]

[0139] In this invention, the antibody titer of the avian influenza oil emulsion inactivated vaccine is positively correlated with the maximum antibody titer index. Within 180 days of immunization, the higher the maximum antibody titer index (regardless of the time of occurrence, generally appearing in the middle of the testing period, for example, day 60), the better the antibody titer of the avian influenza oil emulsion inactivated vaccine.

[0140] Within 180 days of immunization, a maximum antibody titer index of 12.0 or higher indicates extremely high antibody titer in the avian influenza oil-emulsion inactivated vaccine; a maximum antibody titer index below 12.0 but above 11.5 indicates excellent antibody titer; a maximum antibody titer index below 11.5 but above 11.0 indicates good antibody titer; a maximum antibody titer index below 11.0 but above 10.0 indicates average antibody titer; and a maximum antibody titer index below 10.0 indicates poor antibody titer. For highly pathogenic virus vaccines, a higher antibody titer is better.

[0141] As shown in Table 5, the avian influenza oil emulsion inactivated vaccine prepared using the white oil for avian vaccine injection in Examples 1-3 of this invention has excellent antibody titers, and the avian influenza oil emulsion inactivated vaccine prepared using the white oil for avian vaccine injection in Example 4 of this invention has extremely excellent antibody titers. However, the avian influenza oil emulsion inactivated vaccine prepared using the white oil for avian vaccine injection in Comparative Example 1 has only average antibody titers, which is significantly worse.

[0142] As can be seen from Tables 4 and 5, although the absorption performance of the white oil for poultry vaccine injection prepared in Examples 1-4 and Comparative Example 1 can meet the basic requirements for absorption performance of white oil used in highly pathogenic virus vaccines, the antibody titer of the white oil for poultry vaccine injection prepared in Examples 1-4 is much better than that of the white oil for poultry vaccine injection prepared in Comparative Example 1, and it is especially suitable for preparing highly pathogenic virus vaccines.

[0143] Among them, chickens injected with the avian influenza oil emulsion inactivated vaccine prepared using the white oil for avian vaccine injection obtained in Example 4 had an antibody titer of 2 mmol / L 7 days after immunization. 4.0 The antibody titer first reached its lowest level, and after 60 days of immunization, the serum antibody level for avian influenza reached its highest level, with an antibody titer of 2. 12.0 Even 180 days after immunization, the antibody titer remained at 2. 6.0 Above these values, the antibody titer is optimal. Combined with the absorption performance data in Table 4, it can be seen that the white oil for poultry vaccine injection prepared in Example 4 exhibits the best overall performance.

[0144] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A method for preparing white oil for poultry vaccine injection, characterized in that, The method includes the following steps: (1) Using atmospheric and vacuum distillate oil of intermediate base crude oil and / or paraffinic base crude oil as feed oil, the feed oil is contacted with an extractant for extraction treatment to obtain low aromatic oil; (2) The low-aromatic oil is hydrogenated using a hydrogenation catalyst to obtain hydrogenated oil; (3) The hydrotreated oil is subjected to hydrodewaxing treatment using a hydrodewaxing catalyst to obtain hydrodewaxing oil. (4) The hydrodepressed oil is subjected to primary hydrorefining using a primary hydrorefining catalyst to obtain primary hydrorefined oil; (5) The primary hydrorefining product oil is subjected to secondary hydrorefining using a secondary hydrorefining catalyst to obtain a secondary hydrorefining product oil; (6) The oil produced by the secondary hydrorefining is subjected to precision fractionation to obtain white oil for poultry vaccine injection with a distillation range of 310-365℃.

2. The preparation method according to claim 1, wherein, The distillation range of the intermediate-base crude oil's atmospheric and vacuum distillate is 280-420℃, and the distillation range of the paraffin-based crude oil's atmospheric and vacuum distillate is 280-420℃.

3. The preparation method according to claim 1, wherein, The extractant is selected from one or more of furfural, N-methylpyrrolidone, phenol, dimethyl sulfoxide, and sulfolane.

4. The preparation method according to claim 1, wherein, The extraction process conditions include: a mass ratio of extraction solvent to raw oil of 0.5-5:1, an extraction temperature of 40-120℃, and an extraction time of 5-40 min.

5. The preparation method according to claim 1, wherein, The extraction process is a multi-stage centrifugal extraction; The operating conditions for the multi-stage centrifugal extraction include: 10-20 extraction stages, centrifugal speed of 2000-4000 rpm, feed temperature of raw oil of 40-80℃, extraction temperature of 60-100℃, mass ratio of extraction solvent to raw oil of 1-3:1, and contact time of each stage of 10-20 min.

6. The preparation method according to claim 1, wherein, The hydrotreating catalyst comprises 55-80 wt% alumina, 20-40 wt% tungsten oxide and / or nickel oxide, and 0-5 wt% phosphorus pentoxide.

7. The preparation method according to claim 1, wherein, The operating conditions for the hydrotreating include: first pre-sulfurizing the hydrotreating catalyst, and then performing the hydrotreating. The operating conditions for the hydrogenation treatment include: a hydrogen partial pressure of 10-25 MPa, a reaction temperature of 330-430 °C, and a volume hourly space velocity of 0.1-2 h⁻¹. -1 The hydrogen-to-oil volume ratio is 500-3500:

1.

8. The preparation method according to claim 1, wherein, The hydrogen dewaxing catalyst comprises 92-99.5 wt% molecular sieve, 0.5-5.5 wt% nickel oxide, and 0-0.15 wt% copper oxide.

9. The preparation method according to claim 1, wherein, The operating conditions for hydrodewaxing include: first pre-sulfurizing the hydrodewaxing catalyst, and then performing hydrodewaxing treatment; The operating conditions for hydrogen decondensation include: a hydrogen partial pressure of 10-25 MPa, a reaction temperature of 180-300 °C, and a volume hourly space velocity of 0.1-2.5 h⁻¹. -1 The hydrogen-to-oil volume ratio is 300-3500:

1.

10. The preparation method according to claim 1, wherein, The primary hydrorefining catalyst comprises 85-97 wt% alumina; 3-15 wt% molybdenum oxide; and 0.2-2.5 wt% nickel oxide.

11. The preparation method according to claim 1, wherein, The primary hydrorefining catalyst is first pre-sulfurized, and then subjected to a primary hydrorefining process. The operating conditions for the primary hydrogenation purification include: a hydrogen partial pressure of 10-25 MPa, a reaction temperature of 160-320 °C, and a volume hourly space velocity of 0.5-3.5 h⁻¹. -1 The hydrogen-to-oil volume ratio is 300-3500:

1.

12. The preparation method according to claim 1, wherein, The secondary hydrorefining catalyst comprises 94-99.5 wt% alumina, 0.5-2.5 wt% platinum oxide and / or palladium oxide, and 0-0.5 wt% molybdenum oxide.

13. The preparation method according to claim 1, wherein, The operating conditions for the secondary hydrogenation purification include: a hydrogen partial pressure of 10-25 MPa, a reaction temperature of 160-320 °C, and a volume hourly space velocity of 0.1-2.5 h⁻¹. -1 The hydrogen-to-oil volume ratio is 300-3500:

1.

14. The preparation method according to claim 1, wherein, The distillation range of the white oil used for poultry vaccine injection is 320-345℃.

15. A white oil for injecting poultry vaccines, characterized in that, The carbon number distribution of the white oil used for poultry vaccine injection is 14-21; Based on the total mass of the white oil, the white oil contains 70-85 wt% total alkanes, 15-30 wt% total cycloalkanes, and ≤0.01 wt% total aromatics. Based on the total mass of the white oil, the content of the n-alkanes is 5-10 wt%, and the content of the monobranched isoalkanes is ≥35 wt%.

16. The white oil for poultry vaccine injection according to claim 15, wherein, The kinematic viscosity (40℃) of the white oil used for poultry vaccine injection is 4.4-5.1 mm. 2 / s, density d 20 800-815 kg / m 3 The heavy metal content is less than 10 μg / g, the lead content is less than 1 μg / g, the arsenic content is less than 1 μg / g, easy carbides pass, solid paraffin passes, the acidity is neutral, the ultraviolet absorbance (260nm-350nm) is less than 0.01, and the pour point is -26℃ to -18℃.

17. The use of the white oil for avian vaccine injection as described in claims 15 and / or 16 in highly pathogenic virus vaccines.

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