CN108714146A - A kind of ferulic acid pharmaceutical composition and its new application - Google Patents
A kind of ferulic acid pharmaceutical composition and its new application Download PDFInfo
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Abstract
The present invention discloses a kind of composition of prevention radioactivity damage of intestines, and the composition contains the ferulic acid according to the 10-90mg/kg conversions of experiment mice dosage；The composition can be prepared into clinically-acceptable dosage form；Composition of the present invention has the function of that prevention radioactivity damage of intestines, the prevention radioactivity damage of intestines refer to improving capillary injury of blood vessel in intestinal villi, promotes intestinal crypts stem cells hyperplasia, differentiation, mucomembranous epithelial cell is promoted to regenerate；The prevention radioactivity damage of intestines refers to by influencing Thbd-aPC signal paths, improving by the cell state and function according to mouse hemopoietic system；The prevention radioactivity damage of intestines refers to adjusting inflammatory factor HMGB1.
Description
Technical field
The invention belongs to pharmaceutical fields, and in particular to a kind of ferulic acid pharmaceutical composition and its new application.
Background technology
Enteron aisle is extremely sensitive to radiating, and is the most important target organ of radiation injury except hemopoietic system.It is either medical
It irradiates or is surprisingly shone, may lead to radioactivity damage of intestines.Radioactivity damage of intestines is both clinical tumor patient's radiotherapy
In most important side effect and exposure dose limiting factor, and be the one of the major reasons of acute radiation sickness death.80%
The malignant tumor patient for receiving abdomen pelvic cavity fractionated radiation treatments occur Nausea and vomiting, abdominal distension, mucous bloody stool etc. after radiotherapy no
With the radioactivity damage of intestines common sympton of degree；After nuclear explosion, nuclear accident, often it also is difficult to escape by luck by the enteron aisle of photograph person, such as day
, there are the diseases such as serious abdominal pain, diarrhea, mucous bloody stool in 68% victim of this explosion of atomic bomb and 21% survivor
Shape.Therefore, the in-depth of radioactivity damage of intestines pathogenesis and effective protective agents is studied to clinical remission radiotherapy side effect,
Radiotherapy process is promoted, and improves nuclear accident Medical Emergency life-saving technology and has highly important meaning.
Mucous membrane of small intestine metabolic turnover is fast, very sensitive to ionising radiation, is quickly damaged after being illuminated.Brain type, intestines
Type and bone marrow form acute radiation sickness may occur in which the necrosis of mucous membrane of small intestine.It is clinically mainly shown as based on intestinal inflammation
Loss of appetite, nausea and vomiting, abdominal pain diarrhea, mucous bloody stool etc., severe patient is likely to occur entembole, intestinal obstruction；Meanwhile it radiating
Property damage of intestines be often accompanied by the Multi-system injuries such as hematopoiesis, immune, multisystem failure is often died of by photograph person.But it still lacks both at home and abroad
Weary effective radioactivity damage of intestines protective agents.
Invention content
Present invention aims at a kind of composition containing ferulic acid of offer and its in the drug of prevention radioactivity damage of intestines
In application；Purpose of the present invention is to what is be achieved through the following technical solutions：
A kind of composition of prevention radioactivity damage of intestines, the composition contain ferulic acid；The content of the composition ferulic acid
It is converted with metering within 10-90mg/kg/ days according to experiment mice dosage；It is preferred that according to experiment mice dosage 10,30,60,
It is converted with metering within 90mg/kg/ days；The composition can be prepared into clinically-acceptable dosage form；
Application of the composition of the present invention in the drug of prevention radioactivity damage of intestines；The prevention radioactivity intestines damage
Wound refers to preventative before radiation treatment awarding ferulic acid 4-6 times；Radiation treatment starts therapeutic to award ferulic acid 3- for 24 hours afterwards
5 times；The prevention radioactivity damage of intestines refers to improving capillary injury of blood vessel in intestinal villi, the stem cells hyperplasia of promotion intestinal crypts,
Differentiation promotes mucomembranous epithelial cell regeneration；The prevention radioactivity damage of intestines refers to by influencing Thbd-aPC signal paths, changing
Kind cell state and function by according to mouse hemopoietic system；The prevention radioactivity damage of intestines refers to adjusting inflammatory factor HMGB1.
It is of the present invention to refer to according to experiment mice dosage conversions：Dosage=mouse dose (mg/kg) × K of peoplePeople/KMouse
×(WMouse/WPeople)1/3=0.086 × mouse dose (mg/kg)；Wherein K is the constant of each species, and W is weight, KPeople=10.6, KMouse
=9.1, mouse weight WMouseIn terms of 0.02kg, human body weight WPeopleIn terms of 50kg.
Experimental example 1：With 5.5Gy60ICR mouse peripheral bloods determine ferulic acid to prescription as changing after Co gamma-rays irradiates 7 days
Case
Peripheral hemogram is body by changing after ionising radiation the most quickly and significant index, and samples convenient, is easy to
Detection.Early-stage study is found：7 days after irradiation, mouse peripheral blood leukocyte count minimizes, and platelet count also significantly reduces.Institute
With, this research with 7 days mouse peripheral bloods after irradiating as variation is main observation index, determine ferulic acid (Ferulic acid,
FA) the dosage regimen of radiation resistance.By Fig. 2 .B and Fig. 3 .B as it can be seen that 7 days mouse peripheral blood leukocyte counts drastically drop after irradiation
It is low, by (6~18) × 10 of normal control mice9/ L is reduced to 0.8 × 109/ L or less.
According to " dosage regimen is 1. (see Fig. 2 .A) " continuous gavage 8 days.The 7th day after irradiation, tail vein blood detects each group
Mouse peripheral blood as.Although the peripheral white blood cell of ferulic acid 90mg/kg intervention group mouse increases, individual difference is larger；
The comparison of the peripheral white blood cell mesh and number of platelets and irradiation control group of each dosage ferulic acid intervention group mouse, difference are equal
Not statistically significant (P>0.05).(see Fig. 2 .B and C) simultaneously, continuous observation is found, 10~16 days after irradiation, irradiation control
There is death, irradiation model group death ICR mouse 4 in group and low, middle and high dose groups mouse.This prompt, 5.5Gy can be to ICR
Mouse causes serious radiation injury；And 1. the ferulic acid dosage regimen based on treatment is difficult to improve mouse peripheral blood leucocyte
Number and platelet count, can not effectively play radiation resistance.
According to " dosage regimen is 2. (see Fig. 3 .A) ", as shown in Fig. 2-2.B and C, 90mg/ is given once daily in continuous gavage 7 days
The 5.5Gy of kg ferulic acids is significantly increased by according to mouse, leukocyte count and platelet count compared with 5.5Gy irradiation models group, difference tool
Statistically significant (P<0.01).This prompt, prevention+treatment are more advantageous to ferulic acid and promote peripheral white blood cells and platelet count
Increase, to play radiation resistance.
The peripheral hemogram result of comprehensive two kinds of dosage regimens, it is seen that (pre-irradiation is preventative to be awarded using " dosage regimen is 2. "
Ferulic acid 4 times, interval is for 24 hours；1h irradiates after last prevention administration；Irradiation start for 24 hours it is therapeutic award ferulic acid 3 times, be spaced
For 24 hours), it is more advantageous to and improves 5.5Gy by ICR mouse peripheral bloods leukocyte count and platelet count is shone, peripheral hemogram is promoted to restore, from
And more fully play the radiation resistance of ferulic acid.So the later stage investigates ferulic acid and is repaiied to intestinal mucosa injury caused by radiation
When the influence of multiple, hematopoietic function damage and inflammatory reaction, continuous 7 days dosage regimens of this prevention+treatment are mainly used.
Experimental example 2:Ferulic acid is to 5.5Gy60The influence that ICR mouse small intestines are damaged after Co gamma-rays irradiates 7 days
2.1 mouse small intestine pathological changes
As shown in figure 4, (note：# is compared with Normal group, P<0.05, q=5.645；* compared with irradiation model group, P<
0.05；* * are compared with irradiation model group, P<0.001, q=3.037,7.105), 5.5Gy60Co gamma-rays singles full-body exposure 7
After it, the small intestine structure of irradiation model group mouse is imperfect, and intestinal villus shortens, the visible villus fragment to fall off in enteric cavity；
The latent layer thin vessels dilatation and congestion of villus；Body of gland is misaligned, gland epithelial cells hyperplasia while with a large amount of teratocyte shapes
At body of gland endolymph cell hyperplasia；Muscle layer is detached with submucosa.10,30,90mg/kg ferulic acid intervention groups by according to mouse
Small intestine, intervene dosage increase with ferulic acid and gradually restore to normal condition.Compared with irradiation control group, 10mg/kg Ah
Visible villus length increases in the mouse small intestine pathological section of Wei's acid intervention group, density improves, gland epithelial cells hyperplasia, simultaneously
There is regenerated villus；But the mucous epithelium of still visible villus upper end falls off, muscle layer is detached with submucosa and office
The deformity of portion visible lymphocyte aggregation and gland epithelial cells.Increase with the intervention dosage of ferulic acid, 30,90mg/kg Ah
Wei's acid intervention group mouse enteral villus length and form are gradually restored to normal condition, at the same pathological section can in it can be seen that small
Intestinal epithelial cell and glandular epithelial hyperplasia, muscle layer are no longer detached with submucosa.This prompt, ferulic acid may have prevention
The effect of radioactivity damage of intestines.
Vascular endothelial cell density and sequential change in 2.2 mouse small intestine villus
In the intestinal villi of normal mouse, vascular endothelial cell is predominantly located at axis, and continuity is preferable.CD31 is intravascular
The specific expressed albumen of chrotoplast uses Immunohistochemical Method to mark the vascular endothelial cell in intestinal villi, observation with CD31
The density and continuity of vascular endothelial cell in villus, the inflammatory reaction contributed to caused by analyzing radiation are damaged with vascular endothelial cell
The relationship of wound.
As shown in figure 5,5.5Gy607 days after Co gamma-rays single full-body exposures, compared with Normal group, irradiation model group
Mouse villus shortens or largely falls off, and visible fragmentary existing vascular endothelial cell, minute quantity connect into line in remaining villus
Property, this shows that the blood vessel structure in intestinal villi destroys under effects of ionizing radiation completely, and intestinal villus is for blood circulatory disorder
There is obstacle, villus blood supply insufficiency.It is therefore contemplated that the inflammatory reaction of radioactivity damage of intestines is mainly since blood vessel endothelium is thin
The ischemic inflammatory reaction that born of the same parents destroy, enteron aisle blood vessel is induced for blood circulatory disorder.Meanwhile enteron aisle blood supply deficiency can also cause intestines
Crypt Stem Cells dysfunction, proliferation, differentiation slow down, and then lead to intestinal epithelial cell failure.It is daily give 10mg/kg Ah
Wei's acid prevents 4 days and treats 3 days mouse, and not only villus length and quantity increase, but also vascular endothelial cell density in villus
It obviously increases, and continuity enhances.With ferulic acid intervene dosage increase, give 30mg/kg and 90mg/kg ferulic acids prevent and
The mouse for the treatment of, not only fluff structures are relatively more complete, and villus length increases, and vascular endothelial cell density obviously increases, even
Continuous property significantly increases.This prompt can effectively prevent 5.5Gy with the ferulic acid of 30mg/kg or more60Co gamma-rays single whole bodies shine
Capillary injury of blood vessel in the intestinal villi of mouse is penetrated, to promote intestinal crypts stem cells hyperplasia, differentiation, promotes mucomembranous epithelial cell
Regeneration.
Experimental example 3:Ferulic acid is to 5.5Gy60HMGB1 distributions in ICR mouse small intestine villus after Co gamma-rays irradiates 7 days
It influences
Radioactivity damage of intestines is mainly shown as acute and chronic radiation enteritis.It is primarily present in view of HMGB1 in normal cell
In nucleus, and transpositions of the HMGB1 into cytoplasm and extracellular fluid and inflammation are closely related, to the three-dimensional of ferulic acid and HMGB
Structure carries out computer molecule fitting.The results are shown in Figure 6, and ferulic acid can be combined directly with HMGB1, and binding site with
Binding site of the HMGB1 positive inhibitors on the albumen is consistent.Therefore speculate that ferulic acid may have and inhibit HMGB1 dystopys
Effect.Adjusting of the ferulic acid to HMGB1 in radioactivity damage of intestines mouse small intestine mucomembranous cell is further verified with immunofluorescence technique
Effect.As shown in fig. 7, under normal condition, HMGB1 is primarily present in the nucleus of small intestinal epithelial cells.When mouse by
To 5.5Gy60After Co gamma-radiation single full-body exposures, the endonuclear HMGB1 protein contents of small intestinal epithelial cells are a large amount of
It reduces, almost disappears, and also have no that the fluorescence level of HMGB1 albumen increases in cytoplasm, this prompt 7 days mouse small intestines after by photograph
HMGB1 in mucomembranous epithelial cell core may be secreted into extracellular fluid, play corresponding biological function.With irradiation model group
Compare, the ferulic acid intervention group mouse of various concentration, the fluorescence intensity of HMGB1 gradually rises in small intestinal epithelial cells；
There is a small amount of HMGB1 in the only part mucomembranous epithelial cell of 10mg/kg ferulic acid intervention group mouse small intestines；30mg/kg asafoetides
The mouse small intestine mucomembranous epithelial cell core HMGB1 contents of sour intervention group increase compared with 10mg/kg ferulic acid intervention group mouse, and mucous membrane
HMGB1 fluorescence intensities and density increase in epithelial cell；90mg/kg ferulic acids then can further improve in mouse small intestine on mucous membrane
The content of HMGB1 in chrotoplast core.The ionising radiation of this result preliminary identification can induce in enterocyte HMGB1 by nucleus
The interior guess to cell exocrine provides experimental basis for effects of the HMGB1 in radioactivity damage of intestines；Meanwhile by ferulic acid
After intervention in intestinal epithelial cell HMGB1 luciferase expressions observed result as it can be seen that ferulic acid can pass through increase intestinal villi
HMGB1 in nucleus alleviates radioactivity damage of intestines.This may be to promote since ferulic acid inhibits the proinflammatory effect of extracellular HMGB1
Nucleus is returned into HMGB1, to inhibit inflammation, promote cell repair, plays radioactivity damage of intestines preventive and therapeutic effect.
Experimental example 4:Ferulic acid is to 5.5Gy60The influence of ICR mice serum cell factors after Co gamma-rays irradiates 7 days
As shown in fig. 7,5.5Gy607 days after Co gamma-rays single full-body exposures, compared with Normal group, mouse peripheral blood
The content of middle HMGB1 significantly increases, the statistically significant (P of difference<0.01).After ferulic acid is intervened, it is seen that increase with dosage is intervened
Add, HMGB1 contents reduce in mice serum；HMGB1 in 30mg/kg and 90mg/kg ferulic acid intervention group mice serums is opposite
Content is substantially reduced, compared with irradiation model group, the statistically significant (P of difference<0.01)；The especially ferulic acid of 90mg/kg can
The level of Normal group mouse will be reduced to by the relative amount according to HMGB1 in mouse peripheral blood.408 interventions of positive drug
Afterwards, although HMGB1 relative amount decreases, but compared with irradiation model group, has no significant difference.(note：## with it is normal
Control group compares, P<0.01, q=4.561；* compared with 5.5Gy irradiation model groups, P<0.05, q=3.123；* and 5.5Gy
Irradiation model group compares, P<0.01, q=3.644；* * are compared with 5.5Gy irradiation model groups, P<0.001, q=6.122)
As shown in figure 8,5.5Gy irradiation after 7 days, compared with irradiation control group, in mice serum IL-6 relative amounts with Ah
Wei's acid intervenes dosage and increases and reduce, and the IL-6 relative amounts of ferulic acid 90mg/kg intervention group mouse reduce significantly (P<
0.01).This prompt, radiation may induce point of IL-6 while inducing HMGB1 relative amounts to increase by its proinflammatory effect
It secretes.And after HMGB1 contents reduce in serum, the relative amount of IL-6 is remarkably decreased, and difference has statistical significance (P<
0.01).(note：## is compared with Normal group, P<0.01, q=4.298；* is compared with 5.5Gy irradiation model groups, P<0.01,
Q=3.616,3.940)
Complex chart 7 and Fig. 8's as a result, in conjunction with example 3 as a result, initial guess ferulic acid may by inhibit HMGB1 by thin
Karyon is secreted into serum, to alleviate the inflammatory reaction of radiation-actuate, reduces point of other inflammatory factors such as IL-6 in serum
The amount of secreting.
Embodiment 5：Ferulic acid is to 5.5Gy60The influence of ICR mouse bone marrow cells hematopoiesis functions after Co gamma-rays irradiates 7 days
5.1 ferulic acids are to 5.5Gy60The influence of ICR mouse bone marrow cells proliferation of hematopoietic progenitors abilities after Co gamma-rays irradiates 7 days
As shown in table 1, after by 5.5Gy full-body exposures, mouse bone marrow cells proliferation of hematopoietic progenitors ability drastically reduces, irradiation
The CFU-E and BFU-E of the red system of model group, the CFU-GM of grain system are below the 20% of Normal group.Positive drug control group and
The ferulic acid intervention group and irradiation model group comparing difference of 10mg/kg, 30mg/kg, 90mg/kg are not statistically significant, but still
It can be seen that ferulic acid has the trend for improving 5.5Gy full-body exposure mouse bone marrow cells proliferation of hematopoietic progenitors abilities.Wherein, 90mg/
CFU-E, BFU-E and CFU-GM hematopoietic progenitor population number of kg ferulic acid intervention groups are close with positive drug control group, with
Irradiation control group compares, and 3 kinds of hematopoietic progenitor population numbers improve 1 times or more.
1. ferulic acid of table is to 5.5Gy60The influence of 7 days mouse bone marrow cells proliferation of hematopoietic progenitors abilities after the irradiation of Co gamma-rays
Note：Compared with Normal group,###P<0.001.Compared with irradiation model group,*P<0.05。
5.2 ferulic acids are to 5.5Gy60ICR mouse bone marrow polychromatic erythrocytes micronucleus cell rates after Co gamma-rays irradiates 7 days
It influences
Micronucleus cell rate increase is the important behaviour of marrow radiation injury, has apparent agent
Amount-effect relation, can be as the important indicator of evaluation radiation insult.Therefore, this research counts 1000 bones in mouse breastbone
The quantity of micronucleus cell in marrow polychromatic erythrocyte, calculates Micronucleus cell rate, and preliminary assessment marrow is thin
Cellular damage degree.The results are shown in Table 2,7 days after 5.5Gy single full-body exposures, polychromatic erythrocyte in mouse bone marrow of sternum
Micronucleus cell rate about increases 8.5 times, this shows 5.5Gy's60Co gamma-rays can cause bone marrow cells in mice to be damaged.Ferulic acid can drop
Low Micronucleus cell rate, although failing that it is made to be reduced to normal level, 90mg/kg ferulic acid intervention groups
The Micronucleus cell rate of mouse is about reduced to the half of 5.5Gy irradiation model group mouse, and difference has system
Meter learns meaning (P< 0.001).So thinking, ferulic acid has the ability for alleviating bone marrow cell damage.
2. ferulic acid of table is to 5.5Gy60The micronucleus cell rate of 7 days mouse bone marrow polychromatic erythrocytes after the irradiation of Co gamma-rays
It influences
Note：Compared with Normal group,###P<0.05.Compared with irradiation model group, * P<0.05, * * * P<0.001.
5.3 ferulic acids are to 5.5Gy60The influence of ICR bone marrow cells in mice apoptosis is as shown in Figure 9 after Co gamma-rays irradiates 7 days：
(note：## is compared with Normal group, P<0.01；* compared with 5.5Gy irradiation model groups) compared with Normal group, 5.5Gy
7 days after irradiation, the cell proportion of early apoptosis and late apoptic (i.e. in two quadrants in right side) significantly increases in ICR mouse bone marrow cells
Add, difference has statistical significance (P<0.05), this prompts 5.5Gy's60Co gamma-rays can induce bone marrow cells in mice apoptosis,
So that mouse bone marrow cells hematopoiesis function reduces, effectively it can not be proliferated and break up, eventually leading to peripheral white blood cells, blood platelet etc. has
Shape constituent reduction.After the ferulic acid of various concentration is intervened, it is seen that apoptotic cell ratio is reduced in mouse bone marrow cells.With irradiation model group
Compare, the ferulic acid of 10mg/kg can effectively reduce the ratio of viable apoptotic cell, the ferulic acid of 30mg/kg and 90mg/kg
Viable apoptotic cell and non-viable apoptotic cell ratio can be reduced (P simultaneously<0.05), the especially ferulic acid intervention of 90 mg/kg
Afterwards, by the ratio according to early and late apoptotic cell in ICR mouse bone marrow cells restores extremely with to normal control mice early stage and
Non-viable apoptotic cell ratio is close.Therefore, it is considered that：Ferulic acid can be promoted by reducing Apoptosis in Marrow Cells by according to mouse bone marrow cells
Hematopoiesis function reparation, to promote peripheral hemogram to increase.5.4 ferulic acids are to 5.5Gy60ICR mouse after Co gamma-rays irradiates 7 days
The influence of Bone Marrow Cell Cycle
As shown in Figure 10：(note：# is compared with Normal group, P<0.05；* compared with 5.5Gy irradiation model groups, P<
0.05；* is compared with 5.5Gy irradiation model groups, P<0.01) 7 days after 5.5Gy irradiations, mould is irradiated in the comparison with Normal group
The cell proportion of G2/M phases significantly increases in type group mouse bone marrow cells, and difference has statistical significance (P<0.05).Result, it is believed that
5.5Gy60Co gamma-rays can induce the bone marrow cells in mice G2/M phases and block.The bone marrow cells in mice G2/M phases, which block, may be
The major reason of the reduction of 5.5Gy irradiation model group mouse bone marrow cells hematopoiesis functions, peripheral blood visible component reduction.Ferulic acid can have
Effect is reduced by according to the cell proportion blocked in the G2/M phases in bone marrow cells in mice；It is dry that ferulic acid 90mg/kg is especially given once daily
The mouse organized in advance, the cell proportion in the G2/M phases is substantially less than irradiation model group (P in marrow<0.05), and with it is normal right
According to the not statistically significant (P of group comparing difference>0.05).
5.5 ferulic acids are to 5.5Gy60ICR mouse bone marrow cells Thbd protein expressions and serum aPC contain after Co gamma-rays irradiates 7 days
The influence of amount
As shown in Figure 10, after single full-body exposure 5.5Gy irradiates 7 days, Thbd albumen in the bone marrow cell of ICR mouse
Relative expression quantity is down to extremely low.The study find that with the raising of ferulic acid intervention dosage, the table of Thbd albumen in mouse bone marrow cells
It is also increased up to amount.Geiger in 2012 etc. points out that Thbd albumen can effectively protect Hematopoietic Stem/ancestral is thin in Nature medicine
Born of the same parents are from radiation injury.This prompt, ferulic acid is possibly through in the expression quantity protection marrow for improving radioresistance albumen Thbd
Hematopoietic stem/progenitor, the apoptosis of cell and the G2/M phases in marrow of reducing block, to improve the proliferative capacity of myeloid progenitor,
Promote hematopoietic function recovery, improves the content of the tangible cell of peripheral blood.Although existing radioresistance traditional Chinese medicine monomer 408 can carry
High peripheral hemogram improves animal survival rate, but mainly plays radiation resistance by anti-oxidant rather than raising Thbd expression quantity, therefore
And Thbd expression quantity has no raising in positive drug control group mouse bone marrow cells.Meanwhile the endogenous inhibitor of Thbd or HMGB1,
Ferulic acid can reduce the inflammatory factor HMGB1 in serum by improving Thbd protein expression levels.
As shown in figure 12, (note：# is compared with Normal group, P<0.05, q=3.083；* with 5.5Gy irradiation models group ratio
Compared with P<0.05, q=3.075；* * are compared with 5.5Gy irradiation model groups, P<0.001, q=4.697) 7 days after 5.5Gy irradiations,
APC contents significantly reduce (P compared with Normal group in irradiation model group ICR mice serums<0.05).This may be since irradiation makes
The Thbd albumen obtained on cell membrane falls off, and active Thbd albumen is reduced so that and internal PROTEIN C can not be activated, into
And it can not be converted into the active aPC of radioresistance.And compared with irradiation model group, after ferulic acid is intervened, the aPC phases in serum
Dosage raising is intervened with ferulic acid to content and is increased.
To sum up, ferulic acid can promote PROTEIN C to be converted into aPC, and then right by improving Thbd expressing quantities
5.5Gy60The bone marrow cell of Co gamma-rays single full-body exposure mouse plays protective action, and it is extensive to effectively facilitate mouse hemopoietic function
It is multiple.Meanwhile the activation of Thbd-aPC signal paths, the content of inflammatory factor in peripheral blood can be also effectively reduced, to inhibit scorching
Disease is reacted.
Ferulic acid can be improved by according to villus length in mouse small intestine, its form is promoted gradually to restore to normal condition, and
Effectively capillary injury of blood vessel promotes mucomembranous epithelial cell to promote intestinal crypts stem cells hyperplasia, differentiation in prevention intestinal villi
Regeneration；Mechanism of action by preventing ferulic acid radiation enteritis is probed into, the results showed that adjusting inflammatory factor HMGB1 is
Important factor in order；Meanwhile ferulic acid can be improved by influencing Thbd-aPC signal paths by according to the thin of mouse hemopoietic system
Born of the same parents' state and function, and then play radiation resistance from multisystem.
Description of the drawings：
The structural formula of Fig. 1 ferulic acids
1. Fig. 2 ferulic acids are administered by scheme to 5.5Gy60The influence of ICR mouse peripheral blood elephants after Co gamma-rays irradiates 7 days
(A. dosage regimens；B. mouse peripheral blood leukocyte count；C. mouse peripheral blood platelet count)
2. Fig. 3 ferulic acids are administered by scheme to 5.5Gy60The influence of ICR mouse peripheral blood elephants after Co gamma-rays irradiates 7 days
(A. dosage regimens；B. mouse peripheral blood leukocyte count；C. mouse peripheral blood platelet count；Compared with irradiation model group, * * P<
0.01)
Fig. 4 ferulic acids are to 5.5Gy60The influence of 7 days mouse small intestine pathology damages after the irradiation of Co gamma-rays
Fig. 5 ferulic acids are to 5.5Gy60Influence (the CD31 of 7 days ICR mouse small intestine vascular endothelial cells after the irradiation of Co gamma-rays
Label, 100 ×)
The molecule fitted figure of Fig. 6 .1 ferulic acids and HMGB1
Fig. 6 .2 ferulic acids are to 5.5Gy60HMGB1 expression and distribution in 7 days ICR mouse small intestine villus after the irradiation of Co gamma-rays
Influence
Fig. 7 ferulic acids are to 5.5Gy60After the irradiation of Co gamma-rays in 7 days mice serums HMGB1 contents influence
Fig. 8 ferulic acids are to 5.5Gy60After the irradiation of Co gamma-rays in 7 days mice serums IL-6 contents influence
Fig. 9 ferulic acids are to 5.5Gy60The influence of bone marrow cells in mice apoptosis after Co gamma-rays irradiates 7 days
Figure 10 ferulic acids are to 5.5Gy60The influence in 7 days bone marrow cells in mice periods after the irradiation of Co gamma-rays
Figure 11 ferulic acids are to 5.5Gy60The influence of 7 days mouse bone marrow cells Thbd protein expressions after the irradiation of Co gamma-rays
Figure 12 ferulic acids are to 5.5Gy60The influence of 7 days ICR mouse peripheral blood aPC contents after the irradiation of Co gamma-rays
Embodiment 1
A kind of capsule of prevention radioactivity damage of intestines, which contains measures according to experiment mice dosage 10mg/kg/ days
The ferulic acid converted, it is preventative before radiation treatment to award ferulic acid 5 days for preventing radioactivity damage of intestines；Radioactivity
Treatment starts therapeutic to award ferulic acid 4 days for 24 hours afterwards.
Embodiment 2
A kind of tablet of prevention radioactivity damage of intestines, which contains measures according to experiment mice dosage 30mg/kg/ days
The ferulic acid converted, it is preventative before radiation treatment to award ferulic acid 4 days for preventing radioactivity damage of intestines；Radioactivity
Treatment starts therapeutic to award ferulic acid day for 24 hours afterwards.
Embodiment 3
A kind of granule of prevention radioactivity damage of intestines, the granule contain according to experiment mice dosage 60mg/kg/ days
It is preventative before radiation treatment to award ferulic acid 6 days for preventing radioactivity damage of intestines with the ferulic acid converted of metering；
Radiation treatment starts therapeutic to award ferulic acid day for 24 hours afterwards.
Embodiment 4
A kind of microemulsion formulation of prevention radioactivity damage of intestines, the microemulsion formulation contain according to 90 mg/ of experiment mice dosage
Kg/ days with the ferulic acid converted of metering, it is preventative before radiation treatment to award ferulic acid for preventing radioactivity damage of intestines
4 days；Radiation treatment starts therapeutic to award ferulic acid 3 days for 24 hours afterwards.
Claims (10)
1. a kind of composition of prevention radioactivity damage of intestines, it is characterised in that the composition contains ferulic acid.
2. composition as described in claim 1, it is characterised in that the composition contains according to experiment mice dosage 10-90mg/
The kg/ days ferulic acids converted with metering.
3. composition as described in claim 1, it is characterised in that the composition contains according to experiment mice dosage 30mg/kg/
The ferulic acid that daily metering is converted.
4. composition as described in claim 1, it is characterised in that the composition contains according to experiment mice dosage 60mg/kg/
The ferulic acid that daily metering is converted.
5. composition according to any one of claims 1 to 5, it is characterised in that the composition is prepared into clinically-acceptable dosage form.
6. application of the composition according to any one of claims 1 to 5 in the drug of prevention radioactivity damage of intestines.
7. application as claimed in claim 6, it is characterised in that the prevention radioactivity damage of intestines refer to before radiation treatment in advance
Anti- property awards ferulic acid 4-6 days；Radiation treatment starts therapeutic to award ferulic acid 3-5 days for 24 hours afterwards.
8. application as claimed in claim 6, it is characterised in that the prevention radioactivity damage of intestines refers to improving in intestinal villi
Capillary damages, and promotes intestinal crypts stem cells hyperplasia, differentiation, promotes mucomembranous epithelial cell regeneration.
9. application as claimed in claim 6, it is characterised in that the prevention radioactivity damage of intestines refers to by influencing Thbd-
APC signal paths improve by the cell state and function according to mouse hemopoietic system.
10. application as claimed in claim 6, it is characterised in that the prevention radioactivity damage of intestines refers to adjusting inflammatory factor
HMGB1。
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112691098A (en) * | 2021-02-20 | 2021-04-23 | 首都医科大学附属北京中医医院 | Application of ferulic acid in preparation of medicine for treating sepsis intestinal mucosa barrier function damage |
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2018
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112691098A (en) * | 2021-02-20 | 2021-04-23 | 首都医科大学附属北京中医医院 | Application of ferulic acid in preparation of medicine for treating sepsis intestinal mucosa barrier function damage |
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