CN115192736A - Coal-made light white oil nano-emulsion type low-density contrast agent and preparation method thereof - Google Patents
Coal-made light white oil nano-emulsion type low-density contrast agent and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a coal-made light white oil nano-emulsion type low-density contrast agent, which comprises the following components in percentage by weight: the oil phase is coal-made light white oil containing C13-C15 isoparaffin, and the mass percentage content of the isoparaffin in the coal-made light white oil is at least 99%. The invention also provides a preparation method of the nano-emulsion low-density contrast agent. The nano-emulsion low-density contrast agent has the filling capacity of the conventional constant-density and low-density contrast agent for gastrointestinal cavities, can effectively eliminate interference and artifacts on two-dimensional images of positive contrast agents such as barium agents and the like, obviously reduces the CT density value of the gastrointestinal cavity, ensures that the difference between the CT density values of the gastrointestinal cavity and the gastrointestinal wall meets the requirement of 3D reconstruction analysis, has good taste, food-grade raw materials, no bad smell and safety, can prevent moisture absorption in the gastrointestinal cavity, is easy to excrete, has no adverse reaction, and is very suitable for the gastrointestinal tract contrast examination of human bodies.
Description
Technical Field
The invention belongs to the field of X-ray contrast agents, and relates to a coal-made light white oil nano-emulsion low-density contrast agent and a preparation method thereof.
Background
The contrast medium is one of the most commonly used medicines in interventional radiology procedures, and is mainly used for displaying blood vessels and body cavities. There are three types of human gastrointestinal contrast agents currently used in hospitals: high density contrast agents, iso-density contrast agents and low density contrast agents.
High-density contrast agent: such as water-soluble iodine-containing contrast agent, iohexol diluent, barium sulfate suspension, etc. The CT value of the high-density contrast agent is as high as hundreds or even thousands of HUs, a great density difference is generated between the gastrointestinal tract filled with the high-density contrast agent and gastrointestinal wall soft tissue with the CT value of about +20 to +40HU, severe artifacts can be generated at the edge of an image, part of the gastrointestinal wall tissue can be shielded, the gastrointestinal wall is poorly displayed, and after the CT enhanced scan of the abdomen, the density difference is not formed between the filled contrast agent in the gastrointestinal tract and the enhanced lesion on the intestinal wall, so that the lesion cannot be clearly displayed. Also, some high density contrast agents (e.g., iodine) may produce allergic reactions in some patients.
Iso-density contrast agents: the water is the most common constant-density oral contrast agent in clinic, and has the advantages of low price, good taste, good tolerance of patients, easy acceptance and no obvious adverse reaction. However, since water passes through the small intestine quickly and is easily and rapidly absorbed by the small intestine, only a small part of water can reach the ileum and the tail end of the ileum, the small density difference between the water and the gastrointestinal wall tissue is difficult to clearly distinguish fine lesions on the gastrointestinal wall and the adjacent tissues, and in addition, the characteristics of poor adhesion, no viscosity, quick excretion and the like of the water easily generate poor filling in the stomach and intestine, thereby interfering the image quality and the diagnosis of the lesions. Therefore, the disease in the ileum region is easily missed when water is used as a contrast agent. Moreover, the intestinal canal is not uniformly dilated, the dilatation maintaining effect is poor, and partial intestinal canal dilatation is still poor even after medicines such as an enterokinesia inhibitor Shaw 33799 and the like are injected into the intestinal canal intravenously.
Low-density contrast agent: such as lipids, gases. The low-density contrast agent has a negative CT density value, and can reduce the CT density value in the intestinal cavity after entering the intestinal cavity, so that the CT scanning signals in the intestinal cavity and the intestinal wall CT scanning signals generate obvious contrast. Gas low-density contrast agents have not been widely used all the time because partial volume effect is easily formed to influence lesion observation, and in the scanning process, a patient needs to hold breath for 2-5 times, and if the breath holding is discontinuous, image misregistration may occur at the boundary part of the fractional scanning. For example, CN201880025040.8 discloses an oral negative contrast agent for abdominal CT, which is a fluid aqueous foam containing a continuous aqueous liquid phase of air bubbles, and has a CT density value in the range of-300 to-800 HU, and a CT value too low, which also produces certain artifacts, covers gastrointestinal lesion sites and is prone to missed diagnosis compared to gastrointestinal tissues (+ 20 to +40 HU).
Patent CN00122432.8 discloses a low-density gastrointestinal contrast agent and a production method thereof, disclosing a quick-dissolving and 'dry-powdered' low-density gastrointestinal contrast agent, but the contrast agent needs to be mixed by glycerol monooleate, propylene glycol alginate and sodium carboxymethylcellulose in proportion on site and then infused by water at 70-100 ℃, so that the time and inconvenience for field operation are caused, the problem of influence of human factors is also caused, and the requirement of quick diagnosis of digestive tract diseases is not facilitated.
Patent CN98107676.9 discloses a gastrointestinal negative contrast agent and its production method, disclosing a vegetable oil based composition for use as a negative contrast agent for clinical abdominal CT. The contrast agent is prepared with vegetable salad oil 9-18 wt%, tragacanth 0.1-0.9 wt%, gum arabic 1.5-6 wt% and distilled water as main components, and through mixing, grinding and homogenizing emulsification.
CN01135057.1, a spiral CT three-dimensional simulation endoscope contrast agent and a production method thereof, the particle size is 0.005-0.02 mm, the content of non-nano emulsion, liquid paraffin is 70-90%, the content of emulsifier is extremely low, the prepared contrast agent emulsion is easy to separate oil and water, the CT value is unstable, and the liquid paraffin is high, the taste of patients is extremely poor, even the contrast agent can not be orally taken for diagnosis.
The nano-emulsion is a novel drug carrier which is researched more enthusiastically in recent years, can encapsulate drugs in a whole body, transport the drugs to a target site through transdermal, oral or intravenous administration and the like, and then has an effect on pathological changes through a slow release effect. The nano-emulsion is a thermodynamic stable system in which emulsion droplets with the size of l 0-l 00nm are dissolved in a solution, and can form uniform transparent or slightly opalescent liquid. At present, no nano-emulsion low-density contrast agent suitable for human gastrointestinal tract contrast diagnosis is clinically reported.
Disclosure of Invention
The invention aims to provide a coal-made light white oil nano-emulsion type low-density contrast agent and a preparation method thereof according to the defects of the prior art.
According to an aspect of the present invention, there is provided a coal-made light white oil nanoemulsion type low density contrast agent, including: the oil phase is coal-made light white oil containing C13-C15 isoparaffin, and the mass percentage content of the isoparaffin in the coal-made light white oil is at least 99%.
Preferably, the coal-based light white oil is prepared by coal-based Fischer-Tropsch synthesis.
Preferably, the nanoemulsion is of the oil-in-water type.
Preferably, the nanoemulsion-type low-density contrast agent has a CT value of-50 HU to-150 HU, preferably-60 HU to-110 HU, more preferably-70 HU to-110 HU, and still more preferably-75 HU to-110 HU.
Preferably, the nano-emulsion type low-density contrast agent is prepared from the following raw material formula in percentage by mass: oil phase 30-35%, emulsifier 8-10%, auxiliary emulsion 6-8%, and water phase in balance.
Preferably, the emulsifier is selected from one or more of natural surfactants or synthetic surfactants.
Preferably, the synthetic surfactant is a nonionic surfactant, the nonionic surfactant is one or more of SUNSOFT182S, tween-80, span-80, SUNSOFT A-172E and SUNSOFT Q-14S, and more preferably, the nonionic surfactant is one or more of SUNSOFT182S, SUNSOFT A-172E and SUNSOFT Q-14S.
Preferably, the aqueous phase is purified water.
Preferably, the co-emulsion is absolute ethanol.
Preferably, the CT value of the nano-emulsion type low-density contrast agent is between-50 HU and-110 HU.
Preferably, the particle size of the oil phase in the contrast agent is nano-scale, and the particle size is less than 100nm.
According to another aspect of the present invention, the present invention further provides a preparation method of a coal-made light white oil nanoemulsion type low density contrast agent, comprising the steps of:
step S1, mixing an oil phase and an emulsifier, and adding a water phase to generate an emulsion white liquid;
s2, adding an auxiliary emulsion into the milky white liquid, and stirring to form primary emulsion;
and S3, homogenizing and emulsifying the primary emulsion in a high-pressure homogenizer to obtain the nano-emulsion.
Preferably, in the step S1, the method further comprises heating the emulsifier, wherein the heating temperature is determined according to the heating phase transition melting temperature of the emulsifier, and is preferably 70-80 ℃.
Preferably, in the step S2, when the milky white liquid gradually becomes translucent, the colostrum is continuously emulsified for at least 20min under heating.
Preferably, in the step S3, the colostrum is cooled and then the colostrum is subjected to high-pressure homogeneous emulsification.
Preferably, in the step S3, the homogenizing and emulsifying operation is: cooling the colostrum, preferably to 4 deg.C, setting the pressure of high-pressure homogenizer at 600-1000bar, and circulating at least 1-4 times for homogenizing.
Compared with the prior art, the invention has the following beneficial effects:
1) The nano-emulsion type low-density contrast agent is successfully prepared, the nano-emulsion has uniform, semitransparent and clear particle size, good fluidity and good stability, and does not generate the phenomena of layering flocculation and the like after being placed for 3 months; in the aspect of contrast imaging, the prepared nano-emulsion low-density contrast agent has the filling capacity of the conventional constant-density and low-density contrast agent for the intestinal cavity, shows various anatomical relationships of the gastrointestinal cavity and can show various characteristic lesions occurring on the mucosal surface of the gastrointestinal wall; the contrast agent has a proper CT low density value (-60 HU to-110 HU), so that on one hand, the interference and the artifact on a two-dimensional image of positive contrast agents such as barium agents and the like can be effectively eliminated, on the other hand, the CT density value of the intestinal cavity can be obviously reduced, and the difference between the CT density values of the intestinal cavity and the intestinal wall can meet the requirement of 3D reconstruction analysis; can prevent intestinal moisture absorption, and facilitate excretion; especially, when the oil phase based on isoparaffin is adopted, for example, the C13-C15 light white oil with high isomeric content with the mass percent of more than 99 percent is adopted, the appropriate viscosity and fluidity can be obtained, the rapid filling property is good, the wall-hanging property in the gastrointestinal tract after oral infusion is good, and in addition, the nano-emulsion has moderate particle size, is safe, non-toxic and good in stability and is not easy to be absorbed by human bodies.
2) The nano-emulsion type low-density contrast agent has the following taste aspects: compared with the bitter taste of barium, the invention has no bad smell because the raw materials are all food grade, and has no side effects of nausea, vomit, abdominal pain and the like when being taken or poured into the stomach and intestine, and the taste can be improved by adding a proper amount of flavoring agent.
3) The adverse reaction of the nano-emulsion low-density contrast agent is as follows: the main raw material liquid paraffin of the low-density contrast agent related in the invention is a lubricating cathartic, the C13-C15 liquid paraffin with high isomeric content with the mass percentage content of more than 99 percent has better stability, the nano-emulsion has moderate grain diameter, the nano-emulsion has moderate viscosity, better wall-hanging property in gastrointestinal tract and no strong diarrhea effect, and because the inertia is not absorbed by human body, the adverse reaction is only to discharge isotonic intestinal contents without influencing the metabolism balance of water and salt in the body, the product has less adverse reaction and is very suitable for the clinical application examination of human gastrointestinal tract radiography.
4) The nano-emulsion low-density contrast agent has a CT value of-60 HU to-110 HU, is close to the CT value of fat tissue outside the gastrointestinal wall, can form a developing effect that the brightness of the fat tissue inside and outside the gastrointestinal cavity is the same or similar to that of the fat tissue outside the gastrointestinal cavity, and the gastrointestinal cavity is darker inside and outside and the gastrointestinal wall is brighter during CT scanning diagnosis, is similar to the effect of a CT value density contrast map of 'eclipse around the sun', and the effect that the developing of the fat tissue inside and outside the gastrointestinal cavity is darker and the gastrointestinal wall is brighter is beneficial to clinical quick diagnosis, can greatly reduce the dependence on the professional skill of a diagnosis operator, and enables a common doctor or even non-imaging professionals to obtain the same diagnosis conclusion of doctors with rich experience, thereby being beneficial to the doctor to reading.
5) The water phase used by the nano-emulsion low-density contrast agent is pure water, so that the nano-emulsion low-density contrast agent is safe and easy to obtain, and the preparation method is simple. The nano-emulsion low-density contrast agent is convenient to use, and a patient can complete all diagnostic examinations of the stomach and the intestinal tract only by one gastrointestinal tract preparation, so that the influence of the preparation before diagnosis on the patient can be reduced, and the diagnosis efficiency is high.
Drawings
FIG. 1 illustrates the preparation steps of a nanoemulsion-type low-density contrast agent;
fig. 2 is an in vitro colon CT image of the nanoemulsion-type low density contrast agent prepared in embodiment 4 with air and water (in the figure, the contrast agent perfused from left to right is a nanoemulsion-type low density contrast agent, air and water in this order);
fig. 3 is a transverse axial CT image of the gavage intestine of the beagle dog prepared in embodiment 4 as a nano-emulsion type low-density contrast agent (a is stomach, b is intestine);
FIG. 4 is a cross-axis CT plan of a biger dog perfused with aqueous contrast medium and with a portion of the small intestine tissue (a is the stomach and b is the intestine).
Detailed Description
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the embodiments will be briefly described below. It is obvious that the drawings in the following description are only some embodiments of the invention, and that for a person skilled in the art, other drawings can be derived from them without inventive effort.
The present invention is described in detail below with reference to the drawings and the specific embodiments, which are not repeated herein, but the embodiments of the present invention are not limited to the following embodiments.
Preparation method of nano-emulsion type low-density contrast agent
As shown in fig. 1, the preparation method comprises:
step S1, mixing an oil phase (liquid paraffin) and an emulsifier (surfactant), and adding purified water to obtain a milky white liquid;
s2, preparing primary emulsion, namely adding an auxiliary emulsion (absolute ethyl alcohol) into the milky white liquid, and stirring to form primary emulsion;
and S3, preparing the uniform nanoemulsion in a high-pressure homogenizer, and homogenizing and emulsifying the primary emulsion to obtain the nanoemulsion.
In the step S1, the oil phase and the solid emulsifier are mixed, heated and stirred until the emulsifier is almost completely melted, the temperature is kept at about 70-80 ℃, and the water phase with the same temperature is added into the mixed system at one time, so that the system turns into milk white.
And step S2, finally, adding the co-emulsion anhydrous ethanol into the mixed system, gradually changing the mixed system into a semitransparent state along with the prolonging of the stirring time, turning off heating, and continuing to emulsify for 20min to obtain the primary emulsion.
And in the step S3, cooling the primary emulsion to 4 ℃, setting the pressure of a high-pressure homogenizer to be 600-1000bar, and carrying out homogenization for multiple times in a circulating manner to obtain the uniform nano-emulsion. By "circulation" is meant that the homogenizer is such that the emulsion is poured into the homogenizer, forced through the slots and then out, such that one pass is called a cycle. At least 1 cycle, preferably 1 to 4 cycles.
In the present application, homogenization was carried out using an APV-2000 high-pressure homogenizer (Kyoho, yokogaku technologies Co., ltd., beijing).
According to research, the emulsifying temperature is 70-80 ℃, so that the oil phase liquid paraffin emulsion can be ensured to be formed into the small-particle-size nano emulsion at the temperature, namely the temperature range is the phase transition temperature point of the oil phase liquid paraffin emulsion, and the nano emulsion can be ensured to be formed.
Oil phase: the specific performance indexes of the purchased liquid paraffin (white oil) are shown in the following table 1.
TABLE 1 Performance indices of several oil phase liquid Paraffins (white oils)
Emulsifier
SUNSOFT182S, SUNSOFT A-172E and SUNSOFT Q-14S, wherein the emulsifiers are nonionic surfactants purchased from Japan Sun food and research company and belong to high-performance polyglycerol fatty acid ester surfactants, the SUNSOFT182S is polyglycerol-2 stearate, the SUNSOFT 172E is polyglycerol-2 dioleate and the SUNSOFT14S is polyglycerol-10 myristate.
Tween-80 and span-80 are purchased nonionic surfactants, and belong to sorbitan fatty acid ester surfactants.
Auxiliary emulsion: commercial absolute ethanol was purchased.
CT value detection
The CT values of the oil phase and the prepared contrast agent are measured by distinguishing the density difference in the tissue structure according to the difference of the linear absorption coefficient of various tissues to X-ray, converting the absorption coefficient of X-ray into CT value, and defining the CT value of fat as-80 HU to-120 HU. The abdomen conditions (KV 120, mAs200, screw pitch 0.99, rotation time 0.5s and scanning time 3.9 s) are selected by using a cross-radiography uCT760 machine, the die body is placed on a CT machine examining table, a base line is positioned at the head end of the die body, positioning scanning is firstly carried out, then examination is carried out according to an abdomen sequence, the range comprises the whole die body, after the scanning is finished, an image is analyzed by using a cross-radiography post-processing workstation, the image quality is excellent, no interference artifact exists, the density of the die body is uniform, and the CT value can be measured. The key of the CT value measurement technology lies in how to correctly select a Region of Interest (ROI), so that the ROI is placed at the central layer of a phantom CT image, and the approximate sectional area of the center of each layer of scanned image is taken to be about 160mm 2 The range is used as an interest area, the ROI has consistent size and proper area, so that an accurate phantom CT value is obtained and each time of data is recorded.
Intestinal tract in-vitro imaging experiment: and measuring the CT density value in the intestinal cavity after the isolated pig intestine is perfused. Filling fresh isolated pig colon with contrast medium, removing air, tying to fill the intestine section, tightening the other end with the same method, immersing pig intestine in edible oil for CT flat scanning, and recording the CT density value in the intestine cavity, wherein the volume of the filled contrast medium is approximately 200ml for keeping the expansion degree of the intestine cavity basically consistent.
Gastric beagle imaging experiment: and (4) measuring the stomach CT density value by intrabody gavage of the animal dog. The healthy beagle dogs start to eat special semi-fluid cans on the day before the examination, 50ml of 50% magnesium sulfate solution is orally taken for catharsis on the day of the experiment at 15 pm, and 250ml of 20% mannitol injection is orally taken for intestinal canal dilatation after half an hour. During the experiment, firstly, contrast agent air is injected into the experimental dog through a stomach tube, the muscle is injected with Shutai injection for anesthesia, the dog is placed into a special U-shaped groove for pet for fixation, spiral CT scanning imaging is immediately carried out, after the dog revives, the contrast agent warm water is injected through the stomach tube again for anesthesia, and scanning imaging is carried out by the same method. After one week, gastrointestinal tract preparation is performed by the same method, the dogs are 60min before examination, 150ml of contrast agent prepared by oral gavage is used, after anesthesia, spiral CT scanning imaging is performed, and CT values are recorded.
Measurement of particle size
The particle size distribution is one of important indexes for judging whether the prepared contrast agent is stable, an SZ-100V2 nanoparticle analyzer (Shanghai Junacho technology Co., ltd.) is adopted to measure the particle size of the prepared sample (the contrast agent), deionized water is used for diluting the sample by about 1000 times before measurement, the multiple scattering phenomenon in the sample is eliminated, and the measurement is carried out at room temperature.
Viscosity measurement
Dynamic viscosity of the prepared emulsion dynamic viscosity values were measured at 25 ℃ using a rotational viscometer.
Embodiment mode 1
The formula (mass percent) of the nano-emulsion type low-density contrast agent is as follows: the oil phase is coal-made light white oil (35%), emulsifier is SUNSOFT182s (10%), auxiliary emulsion is absolute ethyl alcohol (6%), and the rest is water phase is purified water.
In the embodiment, the coal-based light white oil is the domestic coal-based 95 in the table 1, and the light white oil is prepared by coal-based Fischer-Tropsch synthesis, wherein the kinematic viscosity at 40 ℃ is 2.19mm 2 And/s, the carbon number distribution is C13-C15 alkane, wherein the content of isoparaffin in the alkane is 99.09%, and the CT value of the oil phase stock solution is-255 HU.
The preparation process comprises the following steps:
preparing colostrum: according to the formula of the embodiment, the light white oil made from coal and the solid granular emulsifier are mixed, heated and stirred until the emulsifier is almost completely melted, the temperature is kept at about 70-80 ℃, distilled water with the same temperature is added into the mixed system at one time, the mixed system is stirred until the mixed system becomes milk white, absolute ethyl alcohol is added into the mixed system, the system gradually becomes semitransparent along with the prolonging of the stirring time, the heating is closed, and the emulsification is continued for at least 20min, so that the primary emulsion is obtained.
Preparing a uniform nano-emulsion: and (3) placing the primary emulsion in a refrigerator for rapidly cooling, cooling to 4 ℃, setting the pressure of a high-pressure homogenizer to be 1000bar, and circulating for 3 times for homogenizing to obtain the uniform nano emulsion with the particle size of less than 100nm. The primary emulsion is cooled to 4 ℃, the main purpose is to facilitate the early proceeding of the next homogenization process, and the homogenization is carried out after the temperature reduction, so that the damage to the homogenizer, which is possibly caused by the homogenization operation at high temperature, can be avoided, and the homogenization equipment can be protected by homogenizing the primary emulsion at low temperature.
Through detection, the prepared product has uniform particle size, narrow distribution, 79.1nm of average particle size, 0.088 of polydispersity index PDI, 894mpa.s of dynamic viscosity of the nanoemulsion at 25 ℃, uniform, semitransparent and clear particle size of the nanoemulsion, good fluidity and good stability, does not generate the phenomena of layered flocculation and the like after being placed for 3 months, and the prepared contrast agent meets the requirements of the dosage form of the nanoemulsion.
Through detection, the nano-emulsion low-density contrast agent of the embodiment is measured to be-91.1HU through the intestinal tract in-vitro contrast experiment CT value, the CT value is very close to the CT value of human fat, but the contrast with the CT value of the gastrointestinal wall tissue is large, and the gastrointestinal wall structure can be displayed very clearly.
Embodiment mode 2
The formula (mass percent) of the nano-emulsion type low-density contrast agent is as follows: the oil phase is coal-made light white oil (35%), emulsifier is SUNSOFT A-172E (10%), auxiliary emulsion is absolute ethyl alcohol (6%), and the rest is water phase is purified water.
Compared with embodiment 1, the coal-based light white oil and the method for preparing the contrast agent in the present embodiment are the same as those in embodiment 1, except that the emulsifier is selected from the group consisting of SUNSOFT a-172E in the contrast agent formulation.
Through detection, the prepared product has uniform granularity, narrow distribution, the average grain diameter is 83.6nm, the polydispersity index PDI is 0.083, the dynamic viscosity of the nano-emulsion at 25 ℃ is 890mpa.s, the nano-emulsion has uniform, semitransparent and clear grain diameter, good fluidity and good stability, and the phenomenon of layered flocculation and the like does not occur after the nano-emulsion is placed for 3 months, which indicates that the prepared contrast agent meets the requirements of the nano-emulsion dosage form.
Through detection, the nano-emulsion low-density contrast agent of the embodiment is measured to be-93.3 HU through the CT value of an intestinal tract in-vitro contrast experiment, the CT value is very close to the CT value of human fat, but the contrast with the CT value of gastrointestinal wall tissues is large, and the gastrointestinal wall structure can be very clearly shown.
Embodiment 3
The formula (mass percent) of the nano-emulsion type low-density contrast agent is as follows: the oil phase is coal-made light white oil (35%), emulsifier is SUNSOFT Q-14S (10%), auxiliary emulsion is absolute ethyl alcohol (6%), and the rest is water phase is purified water.
Compared with embodiment 1, the coal-based light white oil and the preparation method of the contrast agent are the same as embodiment 1, except that the emulsifier is SUNSOFT Q-14S in the formula of the contrast agent.
Through detection, the prepared product has uniform granularity, narrow distribution, the average grain diameter of 83.8nm, the polydispersity index PDI of 0.081, the dynamic viscosity of the nanoemulsion at 25 ℃ of 888mpa.s, the grain diameter of the nanoemulsion is uniform, semitransparent, clear, good in fluidity and good in stability, and the phenomenon of layered flocculation and the like does not occur after the nanoemulsion is placed for 3 months, so that the prepared contrast agent meets the requirements of a nanoemulsion dosage form.
Through detection, the nano-emulsion low-density contrast agent of the embodiment is measured to be-90.5HU through the CT value of an intestinal in-vitro contrast experiment, the CT value is very close to the CT value of human fat, but the contrast with the CT value of gastrointestinal wall tissues is large, and the gastrointestinal wall structure can be displayed very clearly.
Embodiment 4
The formula (mass percent) of the nano-emulsion type low-density contrast agent is as follows: the oil phase is coal-made light white oil (35%), and the emulsifier is SUNSOFT A-172E and SUNSOFT Q-14S according to the weight ratio of 1:1 percent (10%), the auxiliary emulsion is absolute ethyl alcohol (6%), and the rest is water phase which is purified water.
Compared with the embodiment 1, the coal-made light white oil and the preparation method of the contrast agent are the same as the embodiment 1 except that the emulsifier in the contrast agent formula is selected from two surfactants of SUNSOFT A-172E and SUNSOFT Q-14S, and the emulsifier is compounded according to the optimal HLB value of the oil phase of 10.5.
Through detection, the prepared product has uniform particle size, narrow distribution, 50.6nm of average particle size, 0.081 polydispersity index PDI, 883mpa.s of dynamic viscosity of the nano-emulsion at 25 ℃, uniform, semitransparent and clear particle size, good fluidity and good stability, and does not generate the phenomena of layered flocculation and the like after being placed for 3 months, which indicates that the prepared contrast agent meets the requirements of the nano-emulsion dosage form.
Through detection, the nano-emulsion low-density contrast agent of the embodiment is measured to be-108HU through the CT value of an intestinal tract in-vitro contrast experiment, the CT value is very close to the CT value of human fat, but the contrast with the CT value of gastrointestinal wall tissues is large, and the gastrointestinal wall structure can be very clearly shown.
As can be seen from FIG. 3, the low-density contrast agent prepared by the present application can fill the intestinal lumen after being perfused into the intestinal lumen, and a CT value contrast graph with dark external adipose tissue and bright gastrointestinal wall in the intestinal lumen is obtained through CT scanning, the CT value contrast graph is similar to a eclipse structure, and since the gastrointestinal lumen tissue of a human body or an animal has a CT value of +20HU to +40HU and the fat CT value of the human body or the animal is about-100 HU, the low-density contrast agent prepared by the present embodiment is used for contrast diagnosis, the CT value of the contrast agent is moderate and is similar to the fat CT value of the human body or the animal, and therefore, the obtained CT value density contrast graph can display the effects of dark external adipose tissue and bright gastrointestinal wall in the intestinal lumen, so the gastrointestinal wall structure can be very clearly presented, and the accurate diagnosis of gastrointestinal tract lesions can be very facilitated.
Embodiment 5
The formula (mass percent) of the nano-emulsion type low-density contrast agent is as follows: the oil phase is coal light white oil (20-25%), emulsifier is SUNSOFT182s (5-30%), emulsion aid is absolute ethyl alcohol (6-8%), and the rest is water phase is purified water.
In the present embodiment, the coal-based light white oil is prepared by coal-based fischer-tropsch synthesis, and is the same as in embodiment 1.
The preparation process comprises the following steps:
preparing primary emulsion: according to the formula of the embodiment, the light white oil made from coal and the emulsifier are mixed and then placed on a heatable magnetic stirrer, the temperature is kept at about 70-80 ℃ while heating and stirring, distilled water with the same temperature is added into the mixed system at one time, the visible system is milk white, finally, absolute ethyl alcohol is added into the mixed system, the system is gradually changed into semitransparent along with the prolonging of stirring time, heating is turned off, and emulsification is continued for 30min, so that the colostrum is obtained.
Preparing a uniform nano-emulsion: cooling the primary emulsion to 4 deg.C, setting pressure of high-pressure homogenizer at 600bar, and circulating for 3 times for homogenizing to obtain uniform nanoemulsion with particle size less than 100nm.
Homogenizing, emulsifying, ultra-cleaning, filtering, sterilizing, and packaging.
The nano emulsion is detected, the prepared product has uniform granularity, narrow distribution, average grain diameter of 60.2nm, polydispersity index PDI of 0.083-0.088, uniform, semitransparent and clear grain diameter of the nano emulsion at 25 ℃, good fluidity, good stability and no layering, and the prepared contrast agent meets the requirements of nano emulsion dosage forms.
Through detection, the CT value of the nano-emulsion type low-density contrast agent of the embodiment is measured to be-46 HU to-59 HU through an intestinal tract in-vitro contrast experiment, the CT value of the low-density contrast agent is relatively close to that of human fat, but the contrast with the CT value of gastrointestinal wall tissues is large, and the clear structure of the gastrointestinal wall can also be presented.
Embodiment 6
The formula (mass percent) of the nano-emulsion type low-density contrast agent is as follows: the oil phase is coal-made light white oil (30%), and the emulsifier is SUNSOFT A-172E and SUNSOFT Q-14S according to the weight ratio of 1:1 percent (10%), the auxiliary emulsion is absolute ethyl alcohol (6%), and the rest is water phase which is purified water.
The oil phase, the emulsifier and the method for preparing the contrast medium in this embodiment are the same as those in embodiment 4, except that the ratio of the oil phase, i.e., the coal-derived light white oil, in the contrast medium formulation is adjusted to 30% different from that in embodiment 4.
Through detection, the prepared product has uniform particle size, narrow distribution, 42.6nm of average particle size, 0.083 of polydispersity index PDI, 208.9mpa.s of dynamic viscosity of the nanoemulsion at 25 ℃, uniform, semitransparent and clear particle size of the nanoemulsion, good fluidity, good stability and no layering, and the prepared contrast agent meets the requirements of a nanoemulsion formulation.
Through detection, the nano-emulsion low-density contrast agent of the embodiment is measured to be-92.99HU through the CT value of an intestinal tract in-vitro contrast experiment, the CT value is very close to the CT value of human fat, but the contrast with the CT value of gastrointestinal wall tissues is large, and the gastrointestinal wall structure can be very clearly shown.
Embodiment 7
The formula (mass percent) of the nano-emulsion type low-density contrast agent is as follows: oil phase (30%) of light white oil prepared from coal, and emulsifier (SUNSOFT A-172E and SUNSOFT Q-14S according to the ratio of 1:1 percent (10%), the auxiliary emulsion is absolute ethyl alcohol (6%), and the rest is water phase which is purified water.
Compared with the embodiment 6, the coal-based light white oil in the embodiment is the domestic coal-based 80 in the table 1, and the light white oil is prepared by coal-based Fischer-Tropsch synthesis, wherein the kinematic viscosity at 40 ℃ is 1.52mm 2 And/s, the carbon number distribution is C12-C13 alkane, wherein the content of isoparaffin in the alkane is 99.13%, and the CT value of the oil phase stock solution is-287 HU.
The preparation process comprises the following steps:
preparing colostrum: according to the formula of the embodiment, the light white oil made from coal and the emulsifier are mixed and then placed on a magnetic stirrer which can be heated, the temperature is kept to be about 70-80 ℃ while heating and stirring, distilled water with the same temperature is added into the mixed system at one time, the visible system becomes milk white, finally, absolute ethyl alcohol is added into the mixed system, the system gradually becomes semitransparent along with the prolonging of the stirring time, the heating is closed, and the emulsification is continued for at least 20min, so that the primary emulsion is obtained.
Preparation of uniform nanoemulsion: cooling the primary emulsion to 4 deg.C, setting pressure of high-pressure homogenizer at 1000bar, and homogenizing for 3 times to obtain uniform nanoemulsion with particle size less than 100nm.
Homogenizing, emulsifying, ultra-cleaning, filtering, sterilizing, and packaging.
Through detection, the prepared product has uniform particle size, narrow distribution, 46.1nm of average particle size, 0.088 of polydispersity index PDI, 838.5mpa.s of dynamic viscosity of the nanoemulsion at 25 ℃, uniform, semitransparent and clear particle size of the nanoemulsion, good fluidity, good stability and no layering, and the prepared contrast agent meets the requirements of the dosage form of the nanoemulsion.
Through detection, the nano-emulsion low-density contrast agent of the embodiment is measured to be-89.74HU through the CT value of an intestinal tract in-vitro contrast experiment, the CT value is very close to the CT value of human fat, but the contrast with the CT value of gastrointestinal wall tissues is large, and the gastrointestinal wall structure can be displayed very clearly.
Compared with embodiment 6, the nanoemulsion prepared by the embodiment has similar CT value and particle size, but has higher dynamic viscosity.
Embodiment 8
The formula (mass percent) of the nano-emulsion type low-density contrast agent is as follows: the oil phase is coal-made light white oil (30%), and the emulsifier is SUNSOFT A-172E and SUNSOFT Q-14S according to the weight ratio of 1:1 percent (10%), the auxiliary emulsion is absolute ethyl alcohol (6%), and the rest is water phase which is purified water.
Compared with the embodiment 6, the coal-made light white oil in the embodiment is the domestic coal-based 60 in the table 1, and the light white oil is prepared by coal-based Fischer-Tropsch synthesis, wherein the kinematic viscosity at 40 ℃ is 1.21mm 2 And/s, the carbon number distribution is C11-C12 alkane, wherein the content of isoparaffin in the alkane is 99.17%, and the CT value of the oil phase stock solution is-299 HU. The preparation method is the same as in embodiment 6.
Through detection, the prepared product has uniform particle size, narrow distribution, 61nm of average particle size, 0.089 of polydispersity index PDI, 2357.2mpa.s of dynamic viscosity of the nanoemulsion at 25 ℃, uniform, semitransparent and clear particle size, good stability and no layering, and the prepared contrast agent meets the requirements of a nanoemulsion formulation.
Through detection, the nano-emulsion type low-density contrast agent of the embodiment is measured to be-92.23 HU through the CT value of an intestinal in-vitro contrast experiment, compared with embodiments 6 and 7, although the nano-emulsion prepared by the embodiment has a better CT value and meets the use requirement of the low-density contrast agent, the CT value is very close to the CT value of human fat, but has a large contrast with the CT value of gastrointestinal wall tissues, and the gastrointestinal wall structure can be very clearly presented. However, the nanoemulsion prepared by this embodiment has a larger particle size and a greatly increased dynamic viscosity, i.e., the nanoemulsion type low-density contrast agent has a reduced fluidity, compared to embodiments 6 and 7.
Embodiment 9
The formula (mass percent) of the low-density contrast agent is as follows: oil phase i.e. liquid paraffin (35%), emulsifier two as suspoft a-172E and suspoft Q-14S according to 1:1 percent (10%), the auxiliary emulsion is absolute ethyl alcohol (6%), and the rest is water phase which is purified water.
In this embodiment the liquid paraffin is a white oil prepared from an indian petroleum refinery imported from table 1, wherein the kinematic viscosity at 40 ℃ is 26.36mm 2 (s), the main carbon number distribution composition is C7 aromatics: 0.35% (v/v), C8 aromatic hydrocarbon: 0.32% (v/v), C9 aromatic hydrocarbon: 0.25% (v/v), 91.41% (v/v) of C12-C23 normal paraffin, 7.67% (v/v) of C12 or above isoalkane, and CT value of oil phase stock solution is-170 HU.
The preparation process comprises the following steps: according to the formula of the embodiment, liquid paraffin and solid granular emulsifier are mixed and heated while stirring until the emulsifier is almost completely melted, the temperature is kept at about 70-80 ℃, distilled water with the same temperature is added into the mixed system at one time, the system becomes milky white, finally absolute ethyl alcohol is added into the mixed system, the system is gradually still opaque milky white as the stirring time is prolonged, heating is stopped, and emulsification is continued for at least 20min, so that the colostrum is obtained. Cooling the primary emulsion to 4 deg.C, setting pressure of high-pressure homogenizer at 1000bar, and homogenizing for 3 times to obtain opaque milky low-density contrast agent emulsion.
The contrast agent emulsion is detected to be a non-nano emulsion, the average grain diameter of the contrast agent emulsion is 432.3nm, the polydispersity index PDI is 0.128, the grain diameter uniformity is poor, the dynamic viscosity of the contrast agent emulsion at 25 ℃ is 115.8mpa.s, the contrast agent emulsion is opaque and milky white, the fluidity is good, the standing emulsion is easy to delaminate, and the stability is poor. The low-density contrast agent prepared by the embodiment has a CT value of-64 HU when the addition amount of liquid paraffin is 35% through an intestinal tract in-vitro contrast experiment, and has a remarkable difference compared with the CT values of-108 HU to-92.99 HU in the embodiments 4 and 7.
Since the liquid paraffin used in the present embodiment has a C12-C23 normal paraffin content of 91% or more, the kinematic viscosity at 40 ℃ is 26.36mm 2 The CT value of the stock solution is much higher than that of the light white oil in embodiments 1 to 12, and therefore, in order to obtain a low-density contrast medium having a value in the range close to the CT value of human fat during the preparation process, it is necessary to add an oil phase having a high compounding ratio, for example, at 35% of the addition amount, the CT value of the low-density contrast medium is-64 HU in an in vitro intestinal contrast experiment, and the oil phase is not easily dispersed in the water phase, and although the viscosity of the system is not increased much (the dynamic viscosity after preparation is 115.8mpa.s), it is impossible to prepare a nano-emulsion type low-density contrast medium, and the wall-hanging effect of the low-density contrast medium after administration is general, and the contrast effect is general.
Considering factors such as the contrast effect of the contrast agent, the preparation process, and the economic problem caused by the oil phase with high proportion, the oil-phase liquid paraffin of the embodiment cannot obtain the nano-emulsion type low-density contrast agent, and the obtained low-density contrast agent has poor stability and poor wall-hanging property, so the liquid paraffin oil phase containing the C12-C23 normal paraffin with high content is not a good alternative.
Embodiment 10
The formula (mass percent) of the low-density contrast agent is as follows: the oil phase, i.e. liquid paraffin (35%), emulsifiers SUNSOFT A-172E and SUNSOFT Q-14S are mixed in a ratio of 1:1 percent (10%), the auxiliary emulsion is absolute ethyl alcohol (6%), and the rest is water phase which is purified water.
In the present embodiment, the liquid paraffin is a petroleum refining product produced in domestic in table 1Preparing white oil with kinematic viscosity of 26.14mm at 40 deg.C 2 (s), the main carbon number distribution composition is C8 aromatics: 0.91% (v/v), C9 aromatic hydrocarbons: 1.83% (v/v), C12-C2375.45% (v/v), C12-C23 isoparaffin 21.81% (v/v), and CT value of oil phase stock solution is-162 HU.
The preparation process comprises the following steps: according to the formula of the embodiment, liquid paraffin and solid granular emulsifier are mixed and heated while stirring until the emulsifier is almost completely melted, the temperature is kept at about 70-80 ℃, distilled water with the same temperature is added into the mixed system at one time, the system becomes milky white, finally absolute ethyl alcohol is added into the mixed system, the system is gradually still opaque milky white as the stirring time is prolonged, heating is stopped, and emulsification is continued for at least 20min, so that the colostrum is obtained. Cooling the primary emulsion to 4 deg.C, setting the pressure of high-pressure homogenizer at 1000bar, and circulating for 3 times for homogenizing to obtain opaque milky-white low-density contrast agent emulsion.
The emulsion is detected to be a non-nano emulsion, the average grain diameter of the contrast agent emulsion is 521.4nm, the polydispersity index PDI is 0.132, the grain diameter uniformity is poor, the dynamic viscosity of the contrast agent emulsion at 25 ℃ is 35.7mpa.s, the contrast agent emulsion is opaque and milky, the fluidity is good, the emulsion is easy to delaminate after standing, and the stability is poor. The low-density contrast agent prepared by the embodiment has a CT value of-58 HU when the addition amount of liquid paraffin is 35% through an intestinal tract in-vitro contrast experiment, and has a remarkable difference compared with the CT values of-108 HU to-92.99 HU in the embodiments 4 and 7.
Since the content of C12-C23 normal paraffin in the liquid paraffin used in the present embodiment is 78% or more, the kinematic viscosity of the liquid paraffin at 40 ℃ is 26.14mm 2 The light white oil is a heavy white oil, which is much larger than the light white oil of embodiments 1 to 12, and therefore, in order to obtain a low-density contrast agent having a value in the range close to the CT value of human fat during the preparation process, it is necessary to add an oil phase having a high compounding ratio, for example, a CT value of-58 HU is obtained by an in vitro intestinal contrast experiment when the low-density contrast agent is added at 35%, and the oil phase is not easily dispersed into the water phase, although the viscosity of the system is not increased much during the preparation process (the preparation process is not increased much) (the light white oil is a heavy white oil)A post-kinetic viscosity of 35.7mpa.s), it was not only impossible to prepare a nano-emulsion type low-density contrast medium, but also the kinetic viscosity of 35.7mpa.s was significantly low after preparation, and therefore, the wall-hanging effect of the low-density contrast medium after gastric lavage and administration was poor and the contrast effect was also poor.
Considering factors such as the contrast effect of the contrast agent, the preparation process, and the economic problem caused by the high-proportion oil phase, the oil-phase liquid paraffin of the embodiment cannot obtain the nano-emulsion type low-density contrast agent, and the obtained low-density contrast agent has poor stability and poor wall-hanging property, so that the domestic liquid paraffin oil phase containing the C12-C23 normal paraffin with higher content is not a good alternative.
Comparative embodiment 1
A gastrointestinal negative contrast agent is prepared according to the method disclosed in patent CN98107676.9, and in the embodiment, the kinematic viscosity of 40 deg.C vegetable salad oil is 31.4mm 2 Has a density of 0.91-0.94kg/L and contains C17 unsaturated fatty glyceride as main ingredient.
According to the contrast agent formula disclosed in patent CN 98107676.9: 9 to 18 percent of plant salad oil, 0.1 to 0.9 percent of tragacanth, 1.5 to 6 percent of gum arabic and the balance of distilled water are mixed, stirred, ground and homogenized and emulsified to obtain the gastrointestinal negative contrast agent, and the detection shows that the obtained opaque white emulsion has the particle size of 0.005 to 0.02mm, namely the particle size is more than 5000nm, and is not a nano-emulsion negative contrast agent, the taste of the contrast agent is poor, and the CT value of an intestinal tract in vitro contrast experiment is-38 HU, the contrast agent cannot provide enough negative density value, cannot obtain the range close to the CT value (-100 HU) of the fat of a human body or an animal, cannot achieve the technical effect of 'daily diet', namely CT scanning images show the contrast effect of dark fat tissue outside in the gastrointestinal cavity and bright gastrointestinal wall, and is easy to cause missed diagnosis.
Contrast results with air and water
The nanoemulsion type low-density contrast agent prepared in embodiment 4 of the present application is selected to perform contrast evaluation of gastrointestinal contrast effect with air and water contrast agents.
In vitro colonography comparisons:
fig. 2 shows the effect of nanoemulsion-type low density contrast agent, water and air on intestinal wall on 2D CT images after perfusion of the intestinal lumen under the scanning parameters of tube voltage (120 keV) and tube current (200 mAs). As can be seen from fig. 2, the intestinal wall of the isolated pig intestine perfused with the nano-emulsion type low density contrast agent is clearly shown; after the water is poured, the contrast between the intestinal wall and the contrast agent in the intestines is too low, so that the intestinal wall cannot be clearly displayed; after air is infused, the density difference formed by the air and the intestinal wall is too large, a remarkable partial volume effect appears, and a part of the intestinal wall is covered, so that the shape of the intestinal wall is displayed incompletely, therefore, the display capability of the nano-emulsion type low-density contrast agent on the isolated intestinal wall is remarkably superior to that of the air and the water. The result shows that the home-made nano-emulsion type low-density contrast agent can obviously improve the imaging effect of the intestinal wall on 2D CT images under different scanning conditions.
Bigeye gastric lavage contrast:
fig. 3 is a transverse axial CT image of the gavage intestine of the beagle dog prepared in embodiment 4 as a nano-emulsion type low-density contrast agent. As can be seen from fig. 3, the nanoemulsion type low-density contrast medium can completely present the form of the plica of the gastric mucosa, and simultaneously has good filling to the small intestine section, uniform density in the intestinal cavity, and low-density images similar to the external fat tissue in the gastrointestinal cavity, so that the form, structure and pathological change image characteristics of the gastric mucosa and the intestinal wall can be visually and clearly highlighted in a CT image, and the early detection rate and diagnosis accuracy of the digestive tract diseases are improved. The nano-emulsion type low-density contrast agent has certain viscosity, so that the possibility that the nano-emulsion type low-density contrast agent passes through or is absorbed quickly at a small intestine part is avoided, and the intestinal cavity is fully expanded; the CT value in the cavity measured by the image is about-108 HU, which is not much different from the external adipose tissue, thereby highlighting the display of the fine structure of the gastrointestinal wall; the contrast agent has certain viscosity, good fluidity, light blue semi-transparent appearance and no dehydration catharsis effect, increases the tolerance of patients, effectively increases the compliance of patients, and is more suitable for being used as a contrast agent for gastrointestinal tract examination.
Fig. 4 is a cross-axis CT plan view of biglet gastric lavage tissue filled with aqueous contrast medium and a part of small intestine tissue, and it can be found from fig. 4 that when the contrast medium is infused into the gastrointestinal tract of the test subject at the same time, the gastrointestinal tract filling is poor due to low viscosity and strong fluidity of water, and the plan view only can identify the approximate contour of the gastrointestinal tract, especially can not display a clear stomach "tooth convex" shaped mucosa, can not distinguish the mucosa in the intestinal cavity, and the intestinal wall and the adjacent organ structures are poor. Therefore, in order to enhance the CT image to display the gastrointestinal mucosa and intestinal wall structures, a blood vessel enhancement contrast agent is clinically needed, so that on one hand, the economic cost is increased, and the cost comprises the cost of liver and kidney function examination, the cost of contrast agent materials, the cost of matched equipment and the like; on the other hand, because part of people have allergy problems to the iodine-containing contrast agents, the safety cost of the checked personnel is increased. Therefore, the nano-emulsion low-density contrast agent prepared by the method has the advantages of safety, low cost, good effect, convenience in use and the like.
Contrast effect analysis
As is clear from the data detection results of the above embodiments 1 to 10 and comparative embodiment 1:
1. for oil phase liquid paraffin, as the carbon number distribution increases, the specific gravity of the oil phase increases, the viscosity of the stock solution increases, the CT value of the stock solution increases (reference CT value = 0), a gastrointestinal tract low density contrast agent (-150 HU to-80 HU) meeting the requirements is prepared, the content of the oil phase needs to be increased, the adjustable space is small during preparation, on one hand, the production cost increases, on the other hand, the preparation process is difficult because the amount of white oil added in the oil phase is large, the viscosity of a mixed system in the preparation process is large, the preparation operation is difficult, even the nano emulsion type low density contrast agent cannot be prepared, and even if the prepared non-nano emulsion type low density contrast agent is prepared, the performance is unstable and the nano emulsion type low density contrast agent is easy to layer (for example, embodiments 9 and 10).
2. The oil phase liquid paraffin has high carbon number, large kinematic viscosity value and poor flowing property, and can form a nano-emulsion effect in the emulsion taking the water phase as a main body, thereby being influenced and not easy to prepare. It is stated that the viscosity of the oil phase liquid paraffin cannot be too great.
3. The oil phase liquid paraffin has high content of isoparaffin, good molecule ductility, weak intermolecular force and easy dispersion, so the oil phase liquid paraffin has good fluidity and good wall-hanging property, is beneficial to forming the nano-emulsion and has high stability; the isoparaffin content is high, the fluidity is good, the kinematic viscosity is reduced, and the CT value of the oil phase stock solution is low; high content of isoalkane, high stability, high safety and low toxicity. In addition, the carbon number distribution of the oil phase liquid paraffin is concentrated and the carbon number is moderate (such as C13-C15), the viscosity of the oil phase liquid paraffin can be reduced, so that better fluidity can be obtained, the oil phase liquid paraffin is easy to disperse in the process of preparing the nano emulsion, especially when the content of isoparaffin is higher (such as the content of isoparaffin is more than 99%), the viscosity of the oil phase liquid paraffin is lower, the safety is high, all evaluation indexes of the prepared nano emulsion meet the quality requirement of the nano emulsion, and the expected contrast effect is achieved when the nano emulsion is used as a contrast agent.
4. The coal-based Fischer-Tropsch synthetic white oil has high isomerization content and is very suitable for preparing the nano-emulsion low-density contrast agent. Compared with other coal-based Fischer-Tropsch synthesized light white oil with carbon number distribution of C11-C12 alkane, C12-C13 alkane and other coal-based Fischer-Tropsch synthesized light white oil, the prepared nanoemulsion has moderate particle size and viscosity, the CT value meets the range from-60 HU to-110 HU, the mobility is good, the wall-hanging property in the gastrointestinal tract is good, the contrast effect is good, and the good industrial application prospect is displayed.
5. Since the liquid paraffin having a high n-alkane content in the oil phase has stronger intermolecular force than that of isoparaffin molecules, the liquid paraffin having a high n-alkane content under the same conditions has a high kinematic viscosity, and thus, it is difficult to emulsify and disperse paraffin molecules in the water phase, and it is difficult to produce a nano-emulsion type low-density contrast agent (for example, embodiments 9 and 10).
6. In comparative embodiment 1, the vegetable salad oil is mainly composed of C17 unsaturated fatty acid glyceride, and because of its high viscosity and high density, the CT value of the prepared contrast agent is far from the target value, i.e. the range close to the CT value of the fat of human or animal, and the nano-emulsion type contrast agent cannot be prepared, and the formula using vegetable salad oil as the oil phase cannot obtain the nano-emulsion gastrointestinal negative contrast agent similar to the one in embodiment 1.
The above description is only an embodiment of the present invention, and is not intended to limit the present invention, and it is obvious to those skilled in the art that various modifications and variations can be made in the present invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A coal-made light white oil nanoemulsion type low-density contrast agent is characterized by comprising the following components in parts by weight: the oil phase is coal-made light white oil containing C13-C15 isoparaffin, and the mass percentage content of the isoparaffin in the coal-made light white oil is at least 99%.
2. The coal-based light white oil nanoemulsion low-density contrast agent as claimed in claim 1, wherein the nanoemulsion low-density contrast agent is prepared from the following raw materials in percentage by mass: oil phase 30-35%, emulsifier 8-10%, auxiliary emulsion 6-8%, and water phase in balance.
3. The coal-based light white oil nanoemulsion low-density contrast agent according to claim 1, wherein the coal-based light white oil is prepared by coal-based fischer-tropsch synthesis.
4. The coal-based light white oil nanoemulsion low-density contrast agent as claimed in claim 1, wherein the nanoemulsion low-density contrast agent has a CT value of-50 HU to-150 HU.
5. The coal-based light white oil nanoemulsion low-density contrast agent as claimed in claim 1, wherein the emulsifier is selected from one or more of natural surfactants or synthetic surfactants.
6. The coal-based light white oil nanoemulsion low-density contrast agent as claimed in claim 1, wherein the aqueous phase is purified water and the auxiliary emulsion is absolute ethyl alcohol.
7. The coal-based light white oil nanoemulsion low-density contrast agent as claimed in any one of claims 1-6, wherein the particle size of the oil phase in the contrast agent is less than 100nm, and the nanoemulsion is of the oil-in-water type.
8. A preparation method for producing the coal-made light white oil nanoemulsion type low-density contrast agent according to any one of claims 1 to 7, comprising the following steps:
step S1, mixing an oil phase and an emulsifier, and adding a water phase to generate an emulsion white liquid;
s2, adding an auxiliary emulsion into the milky white liquid, and stirring to form primary emulsion;
and S3, homogenizing and emulsifying the primary emulsion in a high-pressure homogenizer to obtain the nano-emulsion.
9. The method according to claim 8, wherein the step S1 further comprises heating the emulsifier at a temperature of 70-80 ℃.
10. The method according to claim 8 or 9, wherein in the step S3, the homogeneous emulsification operation is: cooling the primary emulsion to 4 deg.C, setting the pressure of high-pressure homogenizer at 600-1000bar, and homogenizing for at least 1-4 times.
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