CN112618665B - Furfuryl sterol-oryzanol combined medicinal preparation for improving immune response - Google Patents
Furfuryl sterol-oryzanol combined medicinal preparation for improving immune response Download PDFInfo
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Abstract
The application relates to the field of medicines, in particular to a furfuryl sterol-oryzanol combined medicine preparation for improving immune response, which comprises furfuryl sterol and oryzanol, wherein the mass ratio of the furfuryl sterol to the oryzanol is (2.0-1.1): 1. In the application, the combination of the furfuryl sterol and the oryzanol has the effects of improving the immune response of a human body, further improving the immunity of the human body and improving the treatment effect on diseases.
Description
Technical Field
The application relates to the field of medicines, in particular to a furfuryl sterol-oryzanol combined medicine preparation for improving immune response.
Background
Oryzanol is a natural mixture consisting of ferulic acid ester mainly comprising cycloartenyl and ferulic acid ester of sterol, and has obvious curative effect on vegetative nerve disorder, and also has effects of reducing blood lipid and cholesterol.
Oryzanol has natural effect of stimulating metabolism, and the applicant believes that oryzanol has potential as a medicine for improving human immunity and further treating various inflammation and infection symptoms. However, no similar research has been made in the prior art.
Disclosure of Invention
In order to fully exert the application of the oryzanol in improving the immunity of the human body, the application provides a furfuryl sterol-oryzanol combined preparation for improving the immune response.
The application provides a furfuryl sterol-oryzanol combined medicine preparation for improving immune response, which adopts the following technical scheme:
a furfuryl sterol-oryzanol combined medicinal preparation for improving immune response is characterized by comprising furfuryl sterol and oryzanol, wherein the mass ratio of the furfuryl sterol to the oryzanol is (2.0-1.1): 1.
In the technical scheme, the oryzanol and the furfuryl sterol are combined, and the furfuryl sterol contains hormone-like components, has the hormone action and can promote the effect of stimulating the immunity by the oryzanol, so that the oryzanol compound has the effect of treating various inflammations. Meanwhile, the furfuryl sterol is used as a natural plant component, has small side effect and mild effect, and can reduce the stimulation of the oryzanol to the stomach, so that the oryzanol can be fully absorbed by a human body. Through long-term practice, the applicant finds that the combination of the furfuryl sterol and the oryzanol in the proportion of (2.0-1.1) to 1 has the effects of improving the immunity of a human body and promoting the generation of immune response.
In addition, the oryzanol has a good anti-fatigue effect, and the furfuryl sterol can adjust the drug property of the oryzanol, so that the combination of the furfuryl sterol and the oryzanol can improve the energy and the anti-fatigue effect, and is also beneficial to improving the sleep quality of a user.
Preferably, the combined medicinal preparation for improving the immune response by the furfuryl sterol and the oryzanol comprises an outer coating layer containing the furfuryl sterol and an inner filling layer containing the oryzanol, wherein the outer coating layer is coated outside the inner filling layer.
The medicine is made into a structure comprising an outer wrapping layer containing the sitosterol and an inner filling layer containing the oryzanol, and the sitosterol has mild medicinal properties outside, so that compared with the method of respectively eating the sitosterol and the sitosterol or other eating modes, the method can relieve the stimulation effect of the oryzanol on intestines and stomach, and further ensure that the oryzanol can be better absorbed by a human body.
Preferably, the dry weight of the envelope consists of the following mass fractions:
8-15% of talcum powder;
acrylic resin: 15-30%;
furfuryl sterol: 5-8%;
cyclodextrin: 15-20%;
flavoring agent: 0 to 0.2 percent;
other auxiliary agents: 0-8%;
maltitol: and (4) the balance.
The outer coating contains talc and acrylic resin, and can reduce disintegration and release of the medicinal preparation in stomach, and further reduce irritation of oryzanol to stomach. The cyclodextrin is used for loading the furfuryl sterol, the cyclodextrin has strong loading capacity and stable performance, and the cyclodextrin has good biological adaptability and hydrophilicity, so that the furfuryl sterol can be better absorbed by a human body. The maltitol is used as a main carrier, has better dispersibility and inclusion property to the materials, has good processing property and has better affinity with cyclodextrin. The outer cladding layer obtained by the compatibility adjustment has good loading performance on the furfuryl sterol and coating performance on the oryzanol, and has good medication effect.
Preferably, the other auxiliary agents comprise the following components in percentage by mass based on the dry weight of the outer cladding:
glycerol: 0.6-2%;
dextrin: 3-5.5%;
white wax: 0.1 to 0.5 percent.
In the technical scheme, the glycerol and the dextrin are added to further improve the compatibility of a system and the uniformity of a processing process, so that the furfuryl sterol and the cyclodextrin have better dispersing performance in the outer cladding, and the white wax is added to help improve the forming performance and the overall strength of the outer cladding.
Preferably, the inner filling layer is composed of the following components in percentage by mass:
gelatin: 26-35%;
oryzanol: 1-6%;
carob bean gum: 12-18%;
water: and (4) the balance.
The gelatin and the carob bean gum are used as carriers, so that the compatibility of the oryzanol can be improved, the high-temperature resistance effect of the oryzanol is improved, the structural damage of the oryzanol caused in the processing process is reduced, and the effect of enhancing the immune response of the furfuryl sterol-oryzanol combined preparation is improved.
Preferably, the furfuryl sterol-oryzanol combined preparation is prepared by the following steps:
preparing an inner filling layer: adding gelatin, oryzanol and carob gum into water, and stirring to obtain uniform colloidal system; preparing a furfuryl sterol-cyclodextrin system: adding furfuryl sterol and cyclodextrin into water, stirring, and vacuum evaporating at a temperature of not higher than 60 deg.C to dryness;
preparing an outer coating layer: mixing the other components except cyclodextrin and furfuryl sterol in the outer cladding layer, heating for melting, adding a furfuryl sterol-cyclodextrin system, uniformly stirring, injecting into a mold, cooling to solidify, and respectively preparing a receiving main body and a cover plate, wherein the receiving main body is provided with a receiving cavity for receiving the inner filling layer;
coating the outer cladding layer and the inner filling layer: and injecting the inner filling layer into the containing cavity, covering the cover plate on the bearing main body, sealing the containing cavity, heating to melt and connect the cover plate and the bearing main body on the connected surface, and cooling to obtain the combined furfuryl sterol-oryzanol preparation.
According to the technical scheme, the two parts of the outer cladding layer are prepared in a melt injection molding mode, then the inner filling layer is injected into the outer cladding layer, and the inner filling layer and the outer cladding layer are combined, so that heating of the oryzanol can be reduced as much as possible, and the administration effect of the oryzanol is improved. The furfuryl sterol is loaded on the cyclodextrin firstly, and the cyclodextrin can play a role in stabilizing and protecting the furfuryl sterol, so that the furfuryl sterol is not easy to damage in the heating process.
Preferably, in the preparation process of the outer coating, the maltitol is heated to be molten, the acrylic resin is added, the talcum powder and other auxiliary agents are added after the mixture is stirred uniformly, the mixture is continuously stirred to be uniform, then the furfuryl sterol-cyclodextrin system and the flavoring agent are added, the mixture is continuously stirred to be uniform, and then the system is injected into a mold.
In the technical scheme, after the maltitol is melted, the acrylic resin is added firstly, a high molecular system in the acrylic resin can form a certain framework structure in the melted state of the maltitol, and then the talcum powder and other additives are added, so that the talcum powder and other additives are more uniformly distributed in the system. And finally, adding the furfuryl sterol-cyclodextrin system to reduce the heating time of the furfuryl sterol-cyclodextrin system, wherein the cyclodextrin and the maltitol have better compatibility, so that the furfuryl sterol-cyclodextrin system can be well dispersed in the molten state of the maltitol, and can be uniformly dispersed only by short stirring time after being added and quickly enters into a cooling process. The process can improve the retention degree of the effective components in the finally prepared furfuryl sterol-cyclodextrin combined medicinal preparation, reduce the damage of the furfuryl sterol and further improve the effect of the medicament.
Preferably, in the preparation process of the outer cladding, the cooling rate of the molten outer cladding in the mold is 1-1.5 ℃/min, the temperature is reduced to 35-40 ℃, then the temperature is further reduced to 20-25 ℃ by a cold air blowing mode, and the temperature of the cold air is lower than 20 ℃.
Through adopting above-mentioned scheme, make the outer cladding of molten state slowly cool down earlier, rethread cold wind further cools off after 35 ~ 40 ℃, can reduce the phenomenon emergence of outer cladding fracture in the mould, further improve the amount of preserving of oryzanol in the medicine, and then improve the effect of medicine.
Preferably, in the preparation process of the inner filling layer, water is heated to 33-36 ℃, gelatin is added, after stirring for 3-4 min, oryzanol and carob gum are added, stirring is continued for 1-2 min, and then heat preservation and storage are carried out.
According to the technical scheme, gelatin and water are mixed to form a glue component, and then the oryzanol and the carob bean gum are added, wherein the carob bean gum has better biocompatibility and bioactivity, can form a uniform and stable system after being mixed with the gelatin, has better coating and protecting effects on the oryzanol, has higher viscosity, can enable an inner filling layer to form a better colloidal state, is not easy to seep out from an outer coating layer, and further reduces the stimulation of the furfursterol-oryzanol combined medicine preparation to the stomach.
Preferably, in the preparation process of the furfuryl sterol-cyclodextrin system, ultrasonic waves are applied to an aqueous solution containing the furfuryl sterol and the cyclodextrin, and stirring is carried out simultaneously for 2-3 hours.
The cyclodextrin can be better loaded with the furfuryl sterol by ultrasonic assistance, the loading capacity of the furfuryl sterol is improved, and the waste of the medicament in the processing process is reduced.
In summary, the present application has the following beneficial effects:
1. in the application, the purposes of improving the human body immune response and enhancing the human body immunity are realized by combined administration of the furfuryl sterol and the oryzanol.
2. In the application, the outer cladding layer containing the furfuryl sterol and the inner filling layer structure containing the oryzanol are arranged, so that the stimulation of the oryzanol to the stomach can be reduced, the oryzanol and the furfuryl sterol are promoted to be better absorbed by a human body, and the effect of improving the immune response is realized.
3. In the application, the furfuryl sterol is loaded through the cyclodextrin, and the oryzanol is protected by a gelatin system in further setting, so that the oryzanol and the furfuryl sterol are better coated and protected, and the administration effect and the mildness of the furfuryl sterol-oryzanol combined administration preparation are further improved.
Drawings
FIG. 1 is a graph showing the results of experiments in experiment 1 in examples 1 to 5 and comparative examples 1 to 2 of the present application.
Detailed Description
The present application will be described in further detail with reference to examples.
Example 1
A furfuryl sterol-oryzanol combined preparation for improving immune response comprises a furfuryl sterol tablet and a oryzanol tablet, wherein the furfuryl sterol tablet and the oryzanol tablet are both prepared by the following method:
preparing a system of dextrin, mannitol, microcrystalline cellulose, sodium carboxymethylcellulose, sucrose and acrylic resin according to a ratio of 50:15:80:20:60:100, adding the furfuryl alcohol or oryzanol accounting for 1% of the total mass of the materials, mixing and granulating through a high-efficiency granulator, and performing drying, granulating and tabletting to obtain the furfuryl alcohol tablet and the oryzanol tablet respectively. Wherein the acrylic resin is Eudragit E.
The ratio of the amount of furfuryl sterol contained in the furfuryl sterol tablet to the amount of oryzanol contained in the oryzanol tablet is 1.6: 1.
Examples 2 to 4
A combination of furfuryl sterol and oryzanol for enhancing immune response, which is different from example 1 in that the ratio of the amount of furfuryl sterol contained in a furfuryl sterol tablet to the amount of oryzanol contained in a oryzanol tablet is 1.1:1, 1.4:1, 2.0:1, respectively.
Examples 5 to 17
A combined pharmaceutical preparation of furfuryl sterol and oryzanol for improving immune response comprises an outer coating layer containing furfuryl sterol and an inner filling layer containing oryzanol, wherein the specific components of the outer coating layer of furfuryl sterol and the inner filling layer of oryzanol are respectively shown in Table 1.
Table 1, composition tables of examples 5 to 17
In examples 5 to 17, the acrylic resin was Eudragit E, the cyclodextrin was β -cyclodextrin, the flavoring agent was stevioside, and the combined preparation of furfuryl sterol and oryzanol was prepared by the following steps:
preparing an inner filling layer: adding gelatin, oryzanol and carob gum into water, heating to 36 deg.C, stirring for 5min, and standing.
Preparing an outer coating layer: mixing and heating all materials in the outer cladding layer to be molten, stirring for 5min, then injecting into a mold, naturally cooling to 25 ℃ in the mold, respectively manufacturing a bearing main body and a cover plate through different molds, and arranging a containing cavity for containing the inner filling layer on the bearing main body.
Coating the outer cladding layer and the inner filling layer: and injecting the inner filling layer into the containing cavity, covering the cover plate on the bearing main body, sealing the containing cavity, heating to melt and connect the cover plate and the bearing main body, and cooling to obtain the combined furfuryl sterol-oryzanol preparation.
Wherein the mass ratio of the furfuryl sterol contained in the outer cladding layer to the oryzanol in the inner filling layer is 1.6: 1.
Example 18
A combined pharmaceutical preparation of furfuryl sterol and oryzanol for improving immune response is different from that in example 5 in that the inner filling layer is oryzanol powder, the preparation process of the inner filling layer is omitted, and the oryzanol powder is directly added into the accommodating cavity as the inner filling layer in the coating process of the outer coating layer and the inner filling layer.
Example 19
A combination preparation of furfuryl sterol and oryzanol for improving immune response, which is different from example 18 in that the preparation method thereof is as follows:
preparing an inner filling layer: adding gelatin, oryzanol and carob gum into water, heating to 36 deg.C, stirring for 5min, and standing.
Preparing a furfuryl sterol-cyclodextrin system: adding furfuryl sterol and cyclodextrin into water, stirring for 2 hr, and vacuum drying at 55 deg.C to obtain powder.
Preparing an outer coating layer: mixing and heating the furfuryl sterol-cyclodextrin system preparation and other materials in the outer coating layer to be molten, stirring for 5min, then injecting into a mold, naturally cooling to 25 ℃ in the mold, respectively preparing a receiving main body and a cover plate through different molds, wherein the receiving main body is provided with a receiving cavity for receiving the inner filling layer.
Coating the outer cladding layer and the inner filling layer: and injecting the inner filling layer into the containing cavity, covering the cover plate on the bearing main body, sealing the containing cavity, heating to melt and connect the cover plate and the bearing main body, and cooling to obtain the combined furfuryl sterol-oryzanol preparation.
Example 20
A combination preparation of furfuryl alcohol-oryzanol for improving immune response, which is different from example 19 in that ultrasonic waves are applied to an aqueous solution of furfuryl alcohol and cyclodextrin while stirring in the step of preparing the furfuryl alcohol-cyclodextrin system.
Example 21
A combination preparation of furfuryl alcohol-oryzanol for improving immune response, which is different from example 20 in that the stirring time is 3 hours during the preparation of the furfuryl alcohol-cyclodextrin system.
Example 22
A combined medicinal preparation of furfuryl sterol and oryzanol for improving immunoreaction is different from embodiment 20 in that during the preparation process of an outer coating, maltitol is heated to be molten, acrylic resin is added, stirring is carried out for 3min, talcum powder and other auxiliary agents are added, stirring is continued for 2min, a furfuryl sterol-cyclodextrin system and a flavoring agent are added, stirring is carried out for 20s, the system is injected into a mold, the temperature is naturally reduced to 25 ℃ in the mold, a bearing main body and a cover plate are respectively prepared through different molds, and a containing cavity for containing an inner filling layer is formed in the bearing main body.
Example 23
A combined medicinal preparation of furfuryl sterol and oryzanol for improving immunoreaction is different from embodiment 20 in that during the preparation process of an outer coating, maltitol is heated to be molten, acrylic resin and talcum powder are added and stirred for 3min, a furfuryl sterol-cyclodextrin system and other auxiliaries are added and stirred for 2min, a flavoring agent is added and stirred for 20s, the system is injected into a mold, the temperature is naturally reduced to 25 ℃ in the mold, a bearing main body and a cover plate are respectively prepared through different molds, and a containing cavity for containing an inner filling layer is formed in the bearing main body.
Example 24
A furfuryl sterol-oryzanol combined pharmaceutical preparation for improving immune response, which is different from embodiment 22 in that in the preparation process of an outer coating, a mixed system of molten maltitol and other substances is injected into a mold, the mold is placed in a constant-temperature water bath environment, the temperature reduction speed of the mold temperature is controlled to be 1-1.5 ℃/min, the mold temperature is controlled to be 35 ℃, then the mold temperature is further reduced to 20 ℃ by means of cold air blowing, and the temperature of cold air is 15 ℃.
Example 25
A furfuryl sterol-oryzanol combined pharmaceutical preparation for improving immune response, which is different from embodiment 22 in that in the preparation process of an outer coating, a mixed system of molten maltitol and other substances is injected into a mold, the mold is placed in a constant-temperature water bath environment, the temperature reduction speed of the mold temperature is controlled to be 1-1.5 ℃/min, the mold temperature is controlled to be 40 ℃, then the mold temperature is further reduced to 25 ℃ by a cold air blowing mode, and the temperature of the cold air is 18 ℃.
Example 26
A furfuryl sterol-oryzanol combination preparation for improving immune response, which is different from example 24 in that, in the preparation of the inner filling layer, water is first heated to 33 ℃, then gelatin, oryzanol and carob are added to the water, stirred for 5min, and then preserved with heat.
Example 27
A combination preparation of furfuryl alcohol-oryzanol for improving immune response, which is different from example 24 in that water is heated to 33 c first and then gelatin is added in the preparation of the inner filling layer. Stirring for 3min, adding oryzanol and carob bean, stirring for 2min, and storing under constant temperature.
Example 28
A combination preparation of furfuryl alcohol-oryzanol for improving immune response, which is different from example 24 in that water is heated to 36 ℃ first, and then gelatin is added in the preparation of the inner filling layer. Stirring for 4min, adding oryzanol and carob gum, stirring for 1min, and storing under heat preservation.
Example 29
A combination preparation of furfuryl alcohol-oryzanol for improving immune response, which is different from example 24 in that water is heated to 36 ℃ first, and then gelatin is added in the preparation of the inner filling layer. Stirring for 4min, adding oryzanol and carob gum, stirring for 1min, cooling to 20 deg.C, and storing.
Examples 30 to 34
A combination preparation of furfuryl sterol and oryzanol for improving immune response, which is different from example 5 in that the mass ratio of the furfuryl sterol in the outer covering layer to the oryzanol in the inner filling layer is 2.0:1, 1.8:1, 1.4:1 and 1.1:1, respectively.
For the above examples, comparative examples were set as follows, and compared with the above examples.
Comparative example 1
A pharmaceutical preparation which differs from example 1 in that in the furfuryl alcohol tablet, an equal amount of sucrose is used instead of furfuryl alcohol.
Comparative example 2
A pharmaceutical preparation differing from example 1 in that oryzanol is replaced with an equal amount of sucrose in oryzanol tablets.
Comparative example 3
A pharmaceutical preparation which differs from example 5 in that, in the outer coating layer, an equal amount of maltitol is used instead of furfuryl sterol.
Comparative example 4
A pharmaceutical preparation which differs from example 5 in that, in the inner filling layer, oryzanol is replaced by an equal amount of gelatin.
Comparative example 5
A pharmaceutical preparation which is different from example 1 in that the mass ratio of furfuryl sterol to oryzanol is 0.8: 1.
Comparative example 6
A pharmaceutical preparation which is different from example 1 in that the mass ratio of furfuryl sterol to oryzanol is 2.5: 1.
For the above examples and comparative examples, the following experiments were set up and aligned.
Experiment 2, drug disintegration experiment: the pharmaceutical preparations of examples 1 to 29 were immersed in a hydrochloric acid solution having a pH of 1.5 for 2 hours, and then sampled to measure the release amounts of furfuryl sterol and oryzanol by liquid chromatography. Subsequently, the above-mentioned pharmaceutical preparation was taken out from hydrochloric acid and immersed in a phosphate buffer solution having a pH of 6.8, taken out after 60min, and the release rates of furfuryl sterol and oryzanol were measured by liquid chromatography. The release rate is the ratio of the total amount of the furfuryl alcohol or oryzanol dissolved in the solution to the total amount of the furfuryl alcohol and the oryzanol.
Experiment 3, human immunity experiment: the volunteers aged 25-30 years and infected with the viral influenza are selected to take the pharmaceutical preparations in examples 1, 5, 12, 17, 18, 26-34 and 3-4 and placebo tablets prepared from starch respectively, the total taking amount of the furfuryl sterol and the oryzanol of each volunteer is 50mg/(kg d), the pharmaceutical preparations are taken after three meals, 5 volunteers are selected for each pharmaceutical preparation and placebo, blood test and recheck are carried out every day, and the recovery date is recorded. The experiment was stopped when the following occurred:
1. the volunteers had deteriorated disease;
2. severe stomach discomfort in volunteers;
3. the volunteers did not recover after 10 days.
Experiment 4, human body fatigue resistance experiment: selecting volunteers of 30-50 years of age, respectively taking the pharmaceutical preparations of examples 1, 5, 12, 17, 18, 29-34 and 3-4 and placebo tablets prepared from starch, wherein the total daily consumption of furfuryl sterol and oryzanol of each volunteer is 50mg/(kg d), and after taking the tablets continuously for one week, please evaluate the self-fatigue state of the volunteers, and selecting 10 volunteers from each group of examples according to four gears of no obvious change, slight increase of energy, obvious increase of energy and excessive excitation to influence sleep.
The results of experiments 1, examples 1 to 5 and comparative examples 1 to 2 are shown in FIG. 1.
As can be seen from the experimental results in fig. 1, in example 1, the combination of oryzanol and sitosterol, with the mass ratio of the sitosterol to the sitosterol being limited to 2.0 to 1.1:1, effectively enhances the immune response in mice and has the efficacy of enhancing immunity. The principle of the method is that the oryzanol has a certain function of improving immunity, and the furfuryl sterol has a certain hormone function, so that lymphocytes in a body can be further improved on the basis of the existing immune response, and a certain stimulation function is generated, so that the existing immune response in the body is enhanced. In addition, although the furfuryl sterol can play a role of hormone, the furfuryl sterol has mild property, so that side effects are small, and the furfuryl sterol are matched for use, so that the good effect of enhancing the immunity is achieved. The effects of improving immunity were not evident in comparative examples 1 to 2 and comparative examples 5 to 6.
Further, the experimental results of experiment 2 are shown in table 2.
TABLE 2 and Experimental results comparison Table of experiment 2
From the above experimental data, compared with the combined preparation in examples 1 to 4, the administration in the modes of the outer cladding layer and the inner filling layer as in examples 5 to 29 can reduce the release of oryzanol in the stomach environment, thereby reducing the stimulation of the oryzanol on the stomach and improving the mildness of the medicine. In examples 5 to 17, the components of the over cladding layer and the inner filling layer were adjusted, and in the over cladding layer, the acrylic resin and maltitol could improve the overall viscosity and fluidity of the over cladding layer, thereby improving the strength of the over cladding layer and reducing the release of oryzanol. And a small amount of furfuryl sterol is released in the outer coating layer to play a role in warming the stomach and reducing gastrointestinal reactions.
Further, experiment 3 was conducted, and the experimental results are shown in table 3.
TABLE 3 and EXPERIMENT 3 EXPERIMENT RESULT COMPARATIVE TABLE
According to the experimental data, the proportion in the application is selected for administration, so that the rehabilitation time of the viral cold patient can be shortened by improving the autoimmune reaction of the patient, and the effect of rehabilitation as soon as possible is achieved. Compared with the method that the oryzanol and the furfuryl sterol are respectively prepared into the granule for administration, the furfuryl sterol-oryzanol combined preparation is prepared in the modes of the outer coating layer and the inner filling layer, on one hand, the stimulation of the oryzanol on the stomach can be effectively reduced, meanwhile, the loss of the effective components of the oryzanol and the furfuryl sterol in the processing process can be reduced, and the effect of promoting the immunity of the preparation on a human body is improved.
In the preparation process of the inner filling layer, the gelatin and the carob bean gum have the combined action, so that the oryzanol can be well loaded and coated, the absorption of the oryzanol by intestinal tracts is promoted, and the effect of the oryzanol in the aspect of promoting the immune response is further improved. By adjusting the adding sequence and adopting an ultrasonic mode to assist dispersion, the loss of the oryzanol in the preparation process of the medicament is reduced, and the effect of the prepared oryzanol-furfuryl sterol combination medicament on improving the immune response is further improved.
Further, experiment 4 was conducted, and the experimental results are shown in table 5.
TABLE 5 and EXPERIMENT 4 EXPERIMENT RESULT TABLE
According to the experimental data, compared with a blank group and a placebo group, the application adopts a mode of combined administration of oryzanol and furfuryl sterol, so that the energy of the volunteers can be effectively improved, and the fatigue resistance effect is achieved. Compared with the embodiment 1, the embodiment 5 has the advantages that the oryzanol inner filling layer is coated by the furfuryl sterol outer coating layer, so that the stimulation effect of the oryzanol on a human body can be reduced, the drug property is milder, and the volunteers cannot be affected by too much excitement to sleep while the anti-fatigue effect is achieved.
Examples 26 and 28 further adjusted the process to obtain better effect, in comparative example 3 and comparative example 4, furfuryl sterol and oryzanol are respectively lacked, in comparative example 3, because furfuryl sterol is lacked, oryzanol has strong irritation to human body, thus easily causing people to be excited and affecting mental state, the concrete condition is related to the actual condition of volunteers, and in comparative example 4, oryzanol is lacked, thus the anti-fatigue effect cannot be realized.
In conclusion, in the application, the furfuryl sterol and the oryzanol are combined, so that the effect of stimulating the immune response by the oryzanol is improved by the furfuryl sterol, the effects of enhancing the immunity of a human body, improving the disease healing speed and resisting fatigue are realized, and the application prospect is good.
The specific embodiments are only for explaining the present application and are not limiting to the present application, and those skilled in the art can make modifications to the embodiments without inventive contribution as required after reading the present specification, but all the embodiments are protected by patent law within the scope of the claims of the present application.
Claims (2)
1. A furfuryl sterol-oryzanol combined medicinal preparation for improving immune response is characterized by comprising furfuryl sterol and oryzanol, wherein the mass ratio of the furfuryl sterol to the oryzanol is (2.0-1.1): 1;
the combined medicine preparation for improving the immune response by the furfuryl sterol and the oryzanol comprises an outer cladding layer containing the furfuryl sterol and an inner filling layer containing the oryzanol, wherein the outer cladding layer is coated outside the inner filling layer;
the dry weight of the outer coating consists of the following substances in mass fraction:
8-15% of talcum powder;
acrylic resin: 15-30%;
furfuryl sterol: 5-8%;
cyclodextrin: 15-20%;
flavoring agent: 0 to 0.2 percent;
other auxiliary agents: 0 to 8 percent;
maltitol: the balance;
the other auxiliary agents comprise the following components in percentage by mass based on the dry weight of the outer cladding:
glycerol: 0.6-2%;
dextrin: 3-5.5%;
white wax: 0.1-0.5%;
the inner filling layer is composed of the following components in percentage by mass:
gelatin: 26-35%;
oryzanol: 1-6%;
carob bean gum: 12-18%;
water: the balance;
the combined preparation of the furfuryl sterol and the oryzanol for improving the immune response is prepared by the following steps:
preparing an inner filling layer: adding gelatin, oryzanol and carob gum into water, and stirring to obtain uniform colloidal system;
preparing a furfuryl sterol-cyclodextrin system: adding furfuryl sterol and cyclodextrin into water, stirring, and vacuum evaporating at a temperature of not higher than 60 deg.C to dryness;
preparing an outer coating: mixing the other components except cyclodextrin and furfuryl sterol in the outer cladding layer, heating for melting, adding a furfuryl sterol-cyclodextrin system, uniformly stirring, injecting into a mold, cooling to solidify, and respectively preparing a receiving main body and a cover plate, wherein the receiving main body is provided with a receiving cavity for receiving the inner filling layer;
coating the outer cladding layer and the inner filling layer: injecting the inner filling layer into the containing cavity, covering the cover plate on the bearing main body, sealing the containing cavity, heating to melt and connect the cover plate and the bearing main body, and cooling to obtain the combined furfuryl sterol-oryzanol preparation;
during the preparation process of the outer coating, firstly heating maltitol to be molten, adding acrylic resin, stirring uniformly, then adding talcum powder and other auxiliaries, continuously stirring uniformly, then adding a furfuryl sterol-cyclodextrin system and a flavoring agent, continuously stirring uniformly, and then injecting the system into a mold;
in the preparation process of the outer cladding, the cooling rate of the molten outer cladding in a mold is 1-1.5 ℃/min, after the temperature is reduced to 35-40 ℃, the temperature is further reduced to 20-25 ℃ in a cold air blowing mode, and the temperature of cold air is lower than 20 ℃;
in the preparation process of the inner filling layer, water is heated to 33-36 ℃, gelatin is added, after stirring for 3-4 min, oryzanol and carob gum are added, stirring is continued for 1-2 min, and then heat preservation and storage are carried out.
2. The combination preparation of furfuryl alcohol-oryzanol for enhancing immune response as claimed in claim 1, wherein: in the preparation process of the furfuryl sterol-cyclodextrin system, ultrasonic waves are applied to an aqueous solution containing the furfuryl sterol and cyclodextrin, and stirring is carried out simultaneously for 2-3 hours.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69213804D1 (en) * | 1991-03-28 | 1996-10-24 | Rooperol Na Nv | Compositions of phytosterols with phytosterolins as immunomodulators |
| DE69916522D1 (en) * | 1998-02-19 | 2004-05-27 | Mcneil Ppc Inc | Process for the preparation of water-dispersible sterol formulations |
| CN101991127A (en) * | 2009-08-10 | 2011-03-30 | 中国科学院过程工程研究所 | Powdery mixture containing phytosterol and oryzanol and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2419114B2 (en) * | 2009-05-01 | 2019-02-27 | UAS Laboratories LLC | Bacterial compositions for prophylaxis and treatment of degenerative disease |
| CN101744788B (en) * | 2010-01-24 | 2013-12-11 | 山东新时代药业有限公司 | Omeprazole enteric coated tablet and preparation method thereof |
| CN106491552A (en) * | 2016-11-28 | 2017-03-15 | 杭州华东医药集团新五丰药业有限公司 | Bran sterol coated tablet and the drug combination of bran sterol coated tablet and oryzanol tabletses |
| CN110623899A (en) * | 2019-11-04 | 2019-12-31 | 伊粒米(杭州)化妆品有限公司 | Rice-derived skin care composition and preparation method thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69213804D1 (en) * | 1991-03-28 | 1996-10-24 | Rooperol Na Nv | Compositions of phytosterols with phytosterolins as immunomodulators |
| DE69916522D1 (en) * | 1998-02-19 | 2004-05-27 | Mcneil Ppc Inc | Process for the preparation of water-dispersible sterol formulations |
| CN101991127A (en) * | 2009-08-10 | 2011-03-30 | 中国科学院过程工程研究所 | Powdery mixture containing phytosterol and oryzanol and preparation method thereof |
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