阅读说明：本技术 一种高品质药用白油及其制备工艺 (High-quality medicinal white oil and preparation process thereof ) 是由 罗智刚 于 2020-11-26 设计创作，主要内容包括：本发明涉及疫苗佐剂用油领域,尤其涉及一种高品质药用白油及其制备工艺。该高品质药用白油,由碳原子数为17～23的烃类化合物组成。该高品质药用白油的制备方法,首先,是加氢预精制,其目的是在高氢气压力和高温条件下,脱除原料油中的硫、氮、氧等杂原子,从而避免第二段贵金属催化剂中毒,同时还将原料油中的一部分芳烃加氢饱和；然后,将预精制生成油中的芳烃进行加氢饱和,制得医药级白油。本发明所提供的动物疫苗的佐剂类白油,具有禽类机体吸收较好且抗体效价高的特点。(The invention relates to the field of oil for vaccine adjuvants, in particular to high-quality medicinal white oil and a preparation process thereof. The high-quality medicinal white oil consists of hydrocarbon compounds with 17-23 carbon atoms. The preparation method of the high-quality medicinal white oil comprises the steps of firstly, carrying out hydrogenation pre-refining, and aiming at removing hetero atoms such as sulfur, nitrogen, oxygen and the like in the raw oil under the conditions of high hydrogen pressure and high temperature so as to avoid poisoning of a second-stage noble metal catalyst and simultaneously carry out hydrogenation saturation on a part of aromatic hydrocarbon in the raw oil; then, the aromatic hydrocarbon in the pre-refined oil is subjected to hydrogenation saturation to prepare the pharmaceutical white oil. The adjuvant white oil of the animal vaccine provided by the invention has the characteristics of good absorption of poultry organisms and high antibody titer.)

1. A high-quality medicinal white oil is characterized by consisting of hydrocarbon compounds with 17-23 carbon atoms.

2. The high quality medicinal white oil according to claim 1, wherein the hydrocarbon compounds comprise alkane compounds, monocyclic aromatic compounds and fused ring aromatic compounds.

3. The high-quality medicinal white oil according to claim 1, wherein the content ratio of the alkane compound, the monocyclic aromatic compound and the fused ring aromatic compound is (83-89): (3-9): (3-9).

4. The preparation method of the high-quality medicinal white oil is characterized by comprising the following steps of:

(1) mixing the hydrocracking tail oil with the lubricant base oil refined by the solvent and dewaxed by the solvent to prepare mixed fraction;

(2) removing impurities, namely feeding the mixed fraction into a one-stage reactor after passing through a heating furnace, then adding hydrogen into the one-stage reactor, and carrying out hydrogenation pre-refining under the conditions that the hydrogen partial pressure is 16.0-17.0 MPa, the temperature is 195-200 ℃ and a pre-refining catalyst exists to obtain a pre-refined product;

(3) Deep saturation, namely sequentially carrying out steam stripping and fractionation on a pre-refined product, and then sequentially carrying out hydrotreating, isomerization pour point depression and hydrofinishing on a hydrofinished product subjected to sulfur, nitrogen, oxygen and metal impurity removal under the conditions that the hydrogen partial pressure is 18.0-19.0 MPa, the temperature is 220-230 ℃ and a refining catalyst exists;

(4) and taking 300-350 ℃ fraction of the hydrofinished product to prepare the adjuvant white oil of the animal vaccine.

5. The preparation method of the high-quality medicinal white oil according to claim 4, wherein in the step (1), the mass ratio of the hydrocracking tail oil to the lubricant base oil subjected to solvent refining and solvent dewaxing is (10-30): (60-80).

6. The method according to claim 4, wherein in the step (2), the pre-refining catalyst is Pt-Rh and the carrier is SiO₂(ii) a The SiO₂Specific surface area of 285m²·g^-1Pore volume of 0.63 mL. g^-1。

7. The method for preparing high-quality medicinal white oil according to claim 6, wherein in the step (2), the volume space velocity of the one-stage reactor is 0.18-1.0 h^-1。

8. The method for preparing high-quality medicinal white oil according to claim 4, wherein in the step (3), the refined catalyst is Pt-Ni, and the carrier is C; the specific surface area of C is 345m ²·g^-1Pore volume of 0.65 mL. g^-1。

9. The method for preparing high-quality medicinal white oil according to claim 8, wherein in the step (3), the volume space velocity of the two-stage reactor is 0.18-0.5 h^-1。

10. Use of a high quality medicinal white oil, wherein the white oil prepared by the method of any one of claims 4 to 9 is used as an adjuvant for animal vaccines.

Technical Field

The invention relates to the field of oil for vaccine adjuvants, in particular to high-quality medicinal white oil and a preparation process thereof.

Background

The white oil is a special mineral oil product obtained by deeply refining and removing impurities such as sulfur, nitrogen, oxygen, aromatic hydrocarbon and the like. White oils are hydrocarbons, which are composed of two elements, carbon and hydrogen, and are generally composed of paraffins and naphthenes, except for extremely small amounts of impurities. The white oil is colorless, odorless, non-corrosive and chemically inert, and is widely applied to the fields of daily chemical industry, medicine production, food processing, instruments, electric power and the like. The composition structure can be further divided into paraffin-based white oil and naphthenic-based white oil; the paraffin-based white oil has high content of medium paraffin, and the naphthenic white oil has relatively high content of naphthenic hydrocarbon.

The most commonly used adjuvant for the inactivated vaccine for poultry at present is an oil emulsion adjuvant mainly comprising white oil, such as the commonly used inactivated vaccine for avian influenza oil emulsion, the inactivated vaccine for newcastle disease oil emulsion and the like at present. Oil emulsion adjuvants can produce high titer antibodies against a single or multiple antigens with a long immune cycle, and the mechanism of action can be roughly explained as follows: firstly, the specific antigen coated in the oil drop is slowly released, and can continuously stimulate an organism to generate specific immune response; secondly, the oil drops can induce local inflammatory reaction of an organism, so that the proliferation of immune cells is stimulated, and the humoral and cellular immune response is enhanced; thirdly, the specific antigen is coated in the oil drops, so that the specific antigen is prevented from being rapidly decomposed by enzyme in body fluid, the antigen decomposition speed is reduced, and the action time is prolonged; fourthly, the oil emulsion can transport the specific antigen at the injection site to the lymph nodes and spleen of the whole body through the lymphatic system to generate a new stimulus-induced antibody.

The biological activity of the oil emulsion adjuvant has close relation with the viscosity, the type of emulsion, the stability of the emulsifier and the like. Too high a viscosity of the oil emulsion adjuvant affects the structure of the emulsion droplet surfactant, resulting in a decrease in adjuvant activity. Meanwhile, the oil emulsion has too high viscosity and high pour point, which brings difficulty to injection and brings inconvenience to customers in northern winter, in addition, the white oil emulsion inactivated vaccine also has the phenomena of strong toxic and side reaction (allergy), red swelling and suppuration of injection parts and the like, so the problems can be solved if the pour point of the white oil can be reduced, however, the components of the white oil are improved if the pour point of the white oil is reduced, and the white oil belongs to a multi-component organic matter, so the immune promoting effect of the white oil is ensured not to be influenced in the process of technical improvement, and the problems of absorption effect, medicine residue and the like are also considered.

At present, white oil products for poultry vaccine injection in domestic markets are difficult to simultaneously take absorption effect and immune effect (antibody titer) into consideration, and specific reference can be made to the records in articles such as comparative research on preparation of newcastle disease and poultry vaccine immune effect by different white oil adjuvants published in journal of third party of Chinese veterinary medicine-animal medicine subcontract argument and literature, application evaluation of white oil in veterinary vaccines published in journal of petrochemical technology, and the like.

In patent application CN201611017099.1, food-grade white oil and a preparation method thereof are described, wherein the food-grade white oil is obtained by hydrofining naphthenic hydrogenation tail oil, specifically, a white oil hydrogenation technology that uses the grading of noble metal white oil hydrogenation catalysts with different acid strengths and controls the reaction temperature in a reactor by zoning is adopted, so that the catalyst white oil hydrogenation depth is greatly improved, and the capability of effectively removing aromatic hydrocarbons is greatly improved. However, the white oil product obtained by the preparation method has strong naphthenic property, the content of paraffin composed of distillate hydrocarbons is too low, and the content of cycloparaffin is relatively high, so the white oil product is poor in absorption when used for preparing poultry vaccines and is easy to generate inflammatory reaction.

Therefore, how to provide the white oil for poultry vaccine injection, which is better absorbed by poultry organisms and has high antibody titer, is still a problem to be solved at present.

Disclosure of Invention

Technical problem to be solved

Aiming at the defects of the prior art, the invention provides the high-quality medicinal white oil with better body absorption and high antibody titer and the preparation process thereof, and solves the technical problems mentioned in the background technology.

(II) technical scheme

In order to achieve the purpose, the invention is realized by the following technical scheme:

a high-quality medicinal white oil is composed of hydrocarbon compounds with 17-23 carbon atoms.

As a further embodiment of the present invention, the hydrocarbon compounds include alkane compounds, monocyclic aromatic compounds and condensed ring aromatic compounds.

In a further embodiment of the present invention, the content ratio of the alkane compound, the monocyclic aromatic compound and the condensed ring aromatic compound is (83 to 89): (3-9): (3-9).

A preparation method of high-quality medicinal white oil comprises the following steps:

(1) mixing the hydrocracking tail oil with the lubricant base oil refined by the solvent and dewaxed by the solvent to prepare mixed fraction;

(2) removing impurities, namely feeding the mixed fraction into a one-stage reactor after passing through a heating furnace, then adding hydrogen into the one-stage reactor, and carrying out hydrogenation pre-refining under the conditions that the hydrogen partial pressure is 16.0-17.0 MPa, the temperature is 195-200 ℃ and a pre-refining catalyst exists to obtain a pre-refined product;

(3) Deep saturation, namely sequentially carrying out steam stripping and fractionation on a pre-refined product, and then sequentially carrying out hydrotreating, isomerization pour point depression and hydrofinishing on a hydrofinished product subjected to sulfur, nitrogen, oxygen and metal impurity removal under the conditions that the hydrogen partial pressure is 18.0-19.0 MPa, the temperature is 220-230 ℃ and a refining catalyst exists;

(4) and taking 300-350 ℃ fraction of the hydrofinished product to prepare the adjuvant white oil of the animal vaccine.

In a further scheme of the invention, in the step (1), the mass ratio of the hydrocracking tail oil to the lubricant base oil subjected to solvent refining and solvent dewaxing is (10-30): (60-80).

As a further scheme of the invention, in the step (2), the pre-refining catalyst is Pt-Rh, and the carrier is SiO₂；SiO₂Specific surface area of 285m²·g^-1Pore volume of 0.63 mL. g^-1。

As a further scheme of the invention, in the step (2), the volume space velocity of the one-stage reactor is 0.18-1.0 h^-1。

As a further scheme of the invention, in the step (3), the refined catalyst is Pt-Ni, and the carrier is C; c has a specific surface area of 345m²·g^-1Pore volume of 0.65 mL. g^-1。

As a further scheme of the invention, in the step (3), the volume space velocity of the two-stage reactor is 0.18-0.5 h ^-1。

The application of the high-quality medicinal white oil is to use the white oil prepared by the preparation method as an adjuvant of animal vaccines.

(III) advantageous effects

The invention provides high-quality medicinal white oil and a preparation process thereof, and the high-quality medicinal white oil has the following beneficial effects:

(1) the high-quality medicinal white oil is mainly prepared by two stages, wherein the first stage is hydrogenation pre-refining, and aims to remove hetero atoms such as sulfur, nitrogen, oxygen and the like in raw oil under the conditions of high hydrogen pressure and high temperature, so that poisoning of a second-stage noble metal catalyst is avoided, and meanwhile, part of aromatic hydrocarbon in the raw oil is subjected to hydrogenation saturation; after pre-refining, industrial white oil and intermediate products with low sulfur and nitrogen contents can be obtained; the second stage is mainly used for carrying out hydrogenation saturation on the aromatic hydrocarbon in the first stage generated oil to prepare medicinal white oil; and a steam stripping and fractionation are arranged between the first section and the second section, light oil products in reaction products are separated out, and heavy distillate oil with low sulfur and nitrogen content obtained after fractionation is used as feeding materials of the second section.

(2) The vaccine adjuvant white oil prepared by the invention has the advantages of good absorption and high antibody titer, so that the vaccine adjuvant white oil can be well used for preparing poultry vaccines and can replace the vaccine white oil in the current market.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments.

Example 1

A high-quality medicinal white oil is composed of hydrocarbon compounds with 17.5-19 carbon atoms; the hydrocarbon compounds comprise alkane compounds, monocyclic aromatic compounds and fused ring aromatic compounds; the content ratio of the alkane compound, the monocyclic aromatic compound and the fused ring aromatic compound is 84.6: 7.5: 7.5.

a preparation method of high-quality medicinal white oil comprises the following steps:

(1) mixing the hydrocracking tail oil with the lubricant base oil refined by the solvent and dewaxed by the solvent to prepare mixed fraction; the mass ratio of the hydrocracking tail oil to the lubricant base oil subjected to solvent refining and solvent dewaxing is 17: 75;

(2) removing impurities, passing the mixed fraction through a heating furnace, feeding into a one-stage reactor, adding hydrogen into the one-stage reactor, and maintaining hydrogen partial pressure at 16.3MPa, temperature at 199 deg.C and volume space velocity at 0.25h^-1And in the presence of a pre-refining catalyst, carrying out hydrogenation pre-refining to obtain a pre-refined product; the pre-refining catalyst is Pt-Rh supported The body is SiO₂；SiO₂Specific surface area of 285m²·g^-1Pore volume of 0.63 mL. g^-1；

(3) Deep saturation, steam stripping and fractionation are carried out on the pre-refined product, and then the hydrogen partial pressure is 18.3MPa, the temperature is 222 ℃, and the volume space velocity is 0.45h^-1And in the presence of a refining catalyst, sequentially carrying out hydrotreating, isomerization pour point depression and hydrogenation supplementary refining on the hydrogenation pre-refining product from which sulfur, nitrogen, oxygen and metal impurities are removed; the refined catalyst is Pt-Ni, and the carrier is C; c has a specific surface area of 345m²·g^-1Pore volume of 0.65 mL. g^-1；

(4) And (3) taking 315 ℃ fractions of the hydrofinished and refined product to prepare the adjuvant white oil of the animal vaccine.

Example 2

A high-quality medicinal white oil is composed of hydrocarbon compounds with 18-20 carbon atoms; the hydrocarbon compounds comprise alkane compounds, monocyclic aromatic compounds and fused ring aromatic compounds; the content ratio of the alkane compound, the monocyclic aromatic compound and the fused ring aromatic compound is 86.6: 7: 6.

a preparation method of high-quality medicinal white oil comprises the following steps:

(1) mixing the hydrocracking tail oil with the lubricant base oil refined by the solvent and dewaxed by the solvent to prepare mixed fraction; the mass ratio of the hydrocracking tail oil to the lubricant base oil subjected to solvent refining and solvent dewaxing is 22: 78, a nitrogen source;

(2) Removing impurities, passing the mixed fraction through a heating furnace, feeding into a one-stage reactor, adding hydrogen into the one-stage reactor, and maintaining the hydrogen partial pressure at 16.5MPa, the temperature at 198 deg.C, and the volume space velocity at 0.5h^-1And in the presence of a pre-refining catalyst, carrying out hydrogenation pre-refining to obtain a pre-refined product; the pre-refined catalyst is Pt-Rh, and the carrier is SiO₂；SiO₂Specific surface area of 285m²·g^-1Pore volume of 0.63 mL. g^-1；

(3) Deep saturation, steam stripping and separating the pre-refined productDistilling, and distilling at hydrogen partial pressure of 18.5MPa, temperature of 225 deg.C, and volume space velocity of 0.35h^-1And in the presence of a refining catalyst, sequentially carrying out hydrotreating, isomerization pour point depression and hydrogenation supplementary refining on the hydrogenation pre-refining product from which sulfur, nitrogen, oxygen and metal impurities are removed; the refined catalyst is Pt-Ni, and the carrier is C; c has a specific surface area of 345m²·g^-1Pore volume of 0.65 mL. g^-1；

(4) And taking 325 ℃ fraction of the hydrofinished product to prepare the adjuvant white oil of the animal vaccine.

Example 3

A high-quality medicinal white oil is composed of hydrocarbon compounds with 19-22 carbon atoms; the hydrocarbon compounds comprise alkane compounds, monocyclic aromatic compounds and fused ring aromatic compounds; the content ratio of the alkane compound, the monocyclic aromatic compound and the fused ring aromatic compound is 88.6: 5: 6.

A preparation method of high-quality medicinal white oil comprises the following steps:

(1) mixing the hydrocracking tail oil with the lubricant base oil refined by the solvent and dewaxed by the solvent to prepare mixed fraction; the mass ratio of the hydrocracking tail oil to the lubricant base oil which is subjected to solvent refining and solvent dewaxing is 25: 70;

(2) removing impurities, passing the mixed fraction through a heating furnace, feeding into a one-stage reactor, adding hydrogen into the one-stage reactor, and maintaining the hydrogen partial pressure at 16.8MPa, temperature at 196 deg.C and volume space velocity at 0.75h^-1And in the presence of a pre-refining catalyst, carrying out hydrogenation pre-refining to obtain a pre-refined product; the pre-refined catalyst is Pt-Rh, and the carrier is SiO₂；SiO₂Specific surface area of 285m²·g^-1Pore volume of 0.63 mL. g^-1；

(3) Deep saturation, stripping and fractionating the pre-refined product, and performing continuous distillation at hydrogen partial pressure of 18.8MPa, temperature of 228 deg.C and volume space velocity of 0.25h^-1And in the presence of a refining catalyst, sequentially carrying out hydrotreating and isomerization reduction on the hydrogenation pre-refining product from which sulfur, nitrogen, oxygen and metal impurities are removedCondensing and hydrorefining; the refined catalyst is Pt-Ni, and the carrier is C; c has a specific surface area of 345m ²·g^-1Pore volume of 0.65 mL. g^-1；

(4) Taking 340 ℃ fraction of the hydrofinished product to prepare the adjuvant white oil of the animal vaccine.

Comparative example 1

A high-quality medicinal white oil is composed of hydrocarbon compounds with 18-20 carbon atoms; the hydrocarbon compounds comprise alkane compounds, monocyclic aromatic compounds and fused ring aromatic compounds; the content ratio of the alkane compound, the monocyclic aromatic compound and the fused ring aromatic compound is 86.6: 7: 6.

a preparation method of high-quality medicinal white oil comprises the following steps:

(1) mixing the hydrocracking tail oil with the lubricant base oil refined by the solvent and dewaxed by the solvent to prepare mixed fraction; the mass ratio of the hydrocracking tail oil to the lubricant base oil subjected to solvent refining and solvent dewaxing is 22: 78.

comparative example 2

A high-quality medicinal white oil is composed of hydrocarbon compounds with 17.5-19 carbon atoms; the hydrocarbon compounds comprise alkane compounds, monocyclic aromatic compounds and fused ring aromatic compounds; the content ratio of the alkane compound, the monocyclic aromatic compound and the fused ring aromatic compound is 84.6: 7.5: 7.5.

a preparation method of high-quality medicinal white oil comprises the following steps:

(1) Mixing the hydrocracking tail oil with the lubricant base oil refined by the solvent and dewaxed by the solvent to prepare mixed fraction; the mass ratio of the hydrocracking tail oil to the lubricant base oil subjected to solvent refining and solvent dewaxing is 17: 75;

(2) removing impurities, passing the mixed fraction through a heating furnace, then entering a one-stage reactor, then adding hydrogen into the one-stage reactor, and keeping the hydrogen partial pressure at 16.3MPa, the temperature at 199 ℃ and the volume space velocity at 0.25h^-1Under the condition of (1), carrying out hydrogenation pre-refining to obtain a pre-refined product;

(3) deep saturation, steam stripping and fractionation are carried out on the pre-refined product, then the hydrogen partial pressure is 18.3MPa, the temperature is 222 ℃ and the volume space velocity is 0.45h^-1Under the condition (2), sequentially carrying out hydrotreating, isomerization pour point depressing and hydrogenation supplementary refining on the hydrogenation pre-refining product from which sulfur, nitrogen, oxygen and metal impurities are removed;

(4) and (3) taking 315 ℃ fractions of the hydrofinished and refined product to prepare the adjuvant white oil of the animal vaccine.

TABLE 1 physicochemical indices of the raw oils

TABLE 2 physicochemical indices of white oil

The white oils prepared in the above example 2, comparative example 1 and comparative example 2 were compared with the white oils of the same type of imported vaccines on the market, and prepared into animal avian influenza vaccine adjuvants, respectively, and 7-day-old chickens were injected into the thigh by intramuscular injection, 1mL per one injection, and the changes in spirit and feed intake were observed, and thereafter observed after 24, 48, 72 and 120 hours of injection, respectively.

As a result, the vaccine residual amounts in 7 days and 14 days after the injection of the white oil prepared in example 2 were lower than those of the white oil prepared in comparative example 1, comparative example 2 and the reference oil, which indicates that the white oil prepared by the preparation method provided by the present invention is well absorbed by the animal body.

After the white oil prepared by the method is prepared into water-in-oil emulsion and mixed with antigen, the white oil is stable and not easy to delaminate, is easy to inject at a lower temperature, and does not have allergy symptoms.

The high-quality medicinal white oil is mainly prepared by two stages, wherein the first stage is hydrogenation pre-refining, and aims to remove hetero atoms such as sulfur, nitrogen, oxygen and the like in raw oil under the conditions of high hydrogen pressure and high temperature, so that poisoning of a second-stage noble metal catalyst is avoided, and meanwhile, part of aromatic hydrocarbon in the raw oil is subjected to hydrogenation saturation; after pre-refining, industrial white oil and intermediate products with low sulfur and nitrogen contents can be obtained; the second stage is mainly used for carrying out hydrogenation saturation on the aromatic hydrocarbon in the first stage generated oil to prepare medicinal white oil; and a steam stripping and fractionation are arranged between the first section and the second section, light oil products in reaction products are separated out, and heavy distillate oil with low sulfur and nitrogen content obtained after fractionation is used as feeding materials of the second section.

The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.