CN106943564A - Alleviate the amomum fruit volatile oil soft capsule that chemotherapy causes intestinal mucosal injury - Google Patents
Alleviate the amomum fruit volatile oil soft capsule that chemotherapy causes intestinal mucosal injury Download PDFInfo
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- CN106943564A CN106943564A CN201710224798.1A CN201710224798A CN106943564A CN 106943564 A CN106943564 A CN 106943564A CN 201710224798 A CN201710224798 A CN 201710224798A CN 106943564 A CN106943564 A CN 106943564A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
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- A61K9/4866—Organic macromolecular compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
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Abstract
The present invention relates to the amomum fruit volatile oil soft capsule for alleviating chemotherapy cause intestinal mucosal injury.The invention provides purposes of the amomum fruit volatile oil in the medicine for alleviating chemotherapy cause intestinal mucosal injury is prepared, additionally provide a kind of chemotherapy of alleviating and cause soft capsule of intestinal mucosal injury and preparation method thereof, the soft capsule is by active ingredient amomum fruit volatile oil, matrix and by gelatin：Glycerine：Water presses (1 1.5):(0.2‑0.8):The soft capsule shell composition that the ratio of (1 1.5) is made.The amomum fruit volatile oil of the present invention can improve body weight, the decline of appetite caused by the FU of chemotherapeutic 5, the generation of diarrhoea, 5 FU, which can be suppressed, causes the rise of inflammatory factor, reduce the expression of caspase-3, suppress LPS and enter blood, increase the expression of intestines tight junction protein, and then improve the damage by intestinal barrier in rats caused by 5 FU.The amomum fruit volatile oil of the present invention also can be by increasing beneficial bacteria of intestinal tract, and reducing the relative abundance of conditioned pathogen improves the imbalance of gut flora caused by 5 FU, maintains stablizing relatively for intestinal microecology.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, and in particular to alleviates the amomum fruit volatile oil soft capsule that chemotherapy causes intestinal mucosal injury
Agent.
Background technology
Chemotherapy plays an important roll in treating malignant tumor, still, and chemotherapeutics is right while tumour cell is killed
Normal cell also toxic effect.Investigation shows that tumor patient is after Chemotherapy is received, its intestinal barrier function heavy damage,
One side intestinal mucosa effective absorbing area is reduced, and causes absorption of nutrient ingredients obstacle and different degrees of bleeding, diarrhoea, pain
Deng；Flora displacement in the increase of another aspect Intestinal permeabiligy, enteric cavity, the reduction of patient's immunity, increase infection rate and the death rate.Cause
This, improving intestinal mucosal injury caused by chemotherapy and the adverse reaction of associated gastrointestinal road turns into urgent society need.
Fructus amomi (Amomi Fructus) is as one of China's " four great Nan medicines ", and have more than 1300 years medicinal and edible goes through
History.Fructus amomi is Zingiber Amomum herbaceos perennial, warm-natured, pungent, with dampness elimination appetizing, warming spleen and stopping diarrha, regulating the flow of vital energy antiabortive etc.
Effect is the common medicine of Chinese traditional treatment gastrointestinal disease.Modern pharmacological research shows that the principle active component in fructus amomi includes acetic acid
The volatile materials such as borneol acetate, camphor, limonene, borneol, with improvement stomach and intestine function, analgesic, antidiarrheal, point for promoting digestive juice
Secrete, the effect such as regulating intestinal canal flora.Fructus amomi passes through clinical practice all the year round and modern study as conventional medicinal and edible medicinal material
Show that the medicinal material has toxic and side effect small, the significant advantage of drug effect.
Treatment is caused that its therapeutic action of the medicine of intestinal mucosal injury is extremely limited by chemotherapy at present, and effect is also each variant.
Therefore, the highly desirable medicine for obtaining intestinal mucosal injury after a kind for the treatment of chemotherapy of excellent effect.
The content of the invention
The technical problems to be solved by the invention are to overcome the defect of prior art there is provided a kind for the treatment of of excellent effect
The medicine of intestinal mucosal injury after treatment.The present inventor has found that there is amomum fruit volatile oil excellent alleviation chemotherapy to cause intestines to glue by studying
The effect of membrane damage, thus the present invention provides following technical scheme to solve the technical problem：
Purposes of the amomum fruit volatile oil in the medicine for alleviating chemotherapy cause intestinal mucosal injury is prepared, amomum fruit volatile oil is preparing tune
The purposes in gut flora, the medicine for maintaining gut flora to balance is saved, the medicine is the common oral formulations in this area, preferably
For soft capsule.
It is described soft invention also provides a kind of soft capsule for alleviating chemotherapy cause intestinal mucosal injury and preparation method thereof
Capsule is made up of active ingredient, matrix and soft capsule shell, and the active ingredient is amomum fruit volatile oil, and the soft capsule shell is by bright
Glue：Glycerine：Water presses (1-1.5):(0.2-0.8):The ratio of (1-1.5) is made.The matrix include soybean oil, beeswax, gelatin,
One or more in lecithin.
The chemotherapy of alleviating causes the preparation method of soft capsule of intestinal mucosal injury to be：Amomum fruit volatile oil is added into matrix
In, stirring makes it be uniformly dispersed, and crosses colloid mill, is pressed into soft capsule, produces.
Amomum fruit volatile oil used in the present invention can use amomum fruit volatile oil commonly used in the art, can also pass through
It is prepared by following methods：Choose Yunnan and introduce a fine variety Fructus Amomi (Amomun villosum Lour), precision weighs 100g and put after crushing
In round-bottomed flask, plus distilled water 600ml, half an hour is soaked, using extraction by steam distillation 8h, volatile oil is collected, it is anhydrous
Sodium sulphate is stored in -4 DEG C of refrigerators after drying, and produces.
Beneficial effects of the present invention：
The amomum fruit volatile oil of the present invention can improve body weight, the decline of appetite caused by chemotherapeutic 5-FU, and the generation of diarrhoea can
Suppressing 5-FU causes the rise of inflammatory factor, reduces the expression of caspase-3, suppresses LPS and enters blood, increase intestines closely connect
The expression of albumen is connect, and then improves the damage by intestinal barrier in rats caused by 5-FU.In addition, the amomum fruit volatile oil of the present invention
Also can be by increasing beneficial bacteria of intestinal tract, reducing the relative abundance of conditioned pathogen improves the imbalance of gut flora caused by 5-FU,
Maintain stablizing relatively for intestinal microecology.
Brief description of the drawings
Fig. 1 shows amomum fruit volatile oil to each group rat body weight, the influence of appetite.
Fig. 2 shows each group Rat-rectum photo.
Fig. 3 shows each group rat small intestine pathological section (× 10 times).
Fig. 4 shows rat small intestine height of naps/Crypt depth (note：Compared with normal group, * p<0.05, * * p<0.01, * * *
p<0.001, compared with model group, #p<0.05, ##p<0.01, ###p<0.001).
Fig. 5 shows influence (note of the amomum fruit volatile oil to rat blood IL-6, ROS：Compared with normal group, * p<0.05, * * p
<0.01, * * * p<0.001, compared with model group, #p<0.05, ##p<0.01, ###p<0.001).
Fig. 6 shows that influence of the amomum fruit volatile oil to rat small intestine ROS, TNF-α, MPO, NF- κ B (is noted：With normal group phase
Than * p<0.05, * * p<0.01, * * * p<0.001, compared with model group, #p<0.05, ##p<0.01, ###p<0.001).
Fig. 7 shows influence (note of the amomum fruit volatile oil to rat p38MAPK, caspase-3：Compared with normal group, * p<
0.05, * * p<0.01, * * * p<0.001, compared with model group, #p<0.05, ##p<0.01, ###p<0.001).
Fig. 8 show amomum fruit volatile oil to rat enterogenous endotoxin LPS, tight junction protein ZO-1, occludin influence
(note：Compared with normal group, * p<0.05, * * p<0.01, * * * p<0.001, compared with model group, #p<0.05, ##p<
0.01, ###p<0.001).
Fig. 9 shows relative abundance of the enteric microorganism in section's level and category level.
Embodiment
With reference to specific embodiment, the present invention is expanded on further.It should be understood that these embodiments are merely to illustrate the present invention
Rather than limitation the scope of the present invention.The experimental method of unreceipted actual conditions in the following example, generally according to conventional strip
Part or according to the condition proposed by manufacturer.Unless otherwise indicated, otherwise all percentage, ratio, ratio or number is pressed
Weight meter.
Unless otherwise defined, all specialties used in text known to scientific words and one skilled in the art with anticipating
Justice is identical.In addition, any method similar or impartial to described content and material all can be applied in the inventive method.Wen Zhong
Described preferable implementation only presents a demonstration with material to be used.
The preparation of the amomum fruit volatile oil of embodiment 1
Choose Yunnan and introduce a fine variety Fructus Amomi (Amomun villosum Lour), precision weighs 100g and is placed in round bottom after crushing
In flask, plus distilled water 600ml, half an hour is soaked, using extraction by steam distillation 8h, volatile oil, anhydrous sodium sulfate is collected
- 4 DEG C of refrigerators are stored in after drying.
The protective effect that the amomum fruit volatile oil of embodiment 2 is damaged to Intestinal Mucosa caused by 5-FU
(1) preparation of intestinal mucosal injury model and administering mode
Experiment with SD rats 48, set up separately normal group (CON), model group (MOD), positive drug Infantile diarrhea group (CBL,
450mg/kg), amomum fruit volatile oil low dose group (VOA.L, 8mg/kg), amomum fruit volatile oil middle dose group (VOA.M, 16mg/kg),
Amomum fruit volatile oil high dose group (VOA.H, 32mg/kg).In addition to normal group, remaining totally 5 days each group rat chemotherapy time, press daily
Dosage 35mg/kg abdominal cavities injection 5-FU (5-FU).The 4h before chemotherapy, each group gives medicine empty stomach gavage, normal group
With totally 12 days model group gavage isometric physiological saline time.Rat body weight, appetite, observation rat diarrhoea feelings are recorded during experiment
Condition experimental animal was put to death in the 12nd day.
At the end of experiment, intraocular corner of the eyes venous blood collection, 10000r.min-1,4 DEG C of centrifugation 15min take serum, detection IL-6,
ROS contents.
After experiment terminates, after chloraldurate solution anesthetized rat, using disposal vacuum venous blood collection pipe, hepatic portal is taken
Venous blood, 2000r.min-1 centrifugation 10min, takes upper plasma, gut derived exndotoxin (LPS) content is detected using TAL.Take
Away from nearby small intestine 1cm is fixed after 24h in 10% formalin solution at pylorus 10cm, pathological section detection is done.Clip rectum
Part, takes pictures, for observing rat diarrhoea situation.Take part small intestine, PBS washes away intestines Dissolve things inside, shred and weigh 2g crush it is small
Intestines, are put in glass homogenate tube plus 2mlPBS is homogenized manually.4 DEG C of homogenate, centrifuges 10min, takes supernatant under the conditions of 4000r.min-1
Liquid, after being cracked through multigelation twice, inflammatory factor (ROS, NF- κ B, TNF-α), GAP-associated protein GAP enzyme in detection small intestine cells
(MPO, p38MAPK, capase-3) and tight junction protein (ZO-1, occludin) expression.
(2) amomum fruit volatile oil is to rat body weight, appetite, the influence suffered from diarrhoea
As shown in Figure 1, amomum fruit volatile oil can effectively reverse rat body weight, the reduction of appetite caused by 5-FU, and to volatilize
Oily high dose group fruit is the most notable.Meanwhile, shown by Fig. 2 rectum photos, after 5-FU is given, serious abdomen occur in model group rats
Rush down, and normal group and each treatment group can be observed substantially to be molded excrement, point out amomum fruit volatile oil to prevent rat caused by 5-FU
The generation of diarrhoea.
(3) influence of the amomum fruit volatile oil to Intestinal Mucosa changes in histopathology
As shown in figure 3, compared with normal group, giving the obvious atrophy of model group small intestine in rats after 5-FU, part fine hair
Come off, shorten, epithelial cell denaturation, necrosis, crypts increase, and each treatment group can substantially reverse the disease that small intestine occurs upon administration
Become.Equally, it can be shown by crypts ratio, what the rat small intestine fine hair that each treatment group can substantially resist 5-FU inductions was reduced shows
As (Fig. 4), and certain dose relationship is presented in amomum fruit volatile oil group.
(4) influence of the amomum fruit volatile oil to rat blood inflammatory factor
As shown in Figure 5, amomum fruit volatile oil can significantly reduce the concentration of proinflammatory factor IL-6, ROS in blood, and with high dose
Effect is more notable.
(5) influence of the amomum fruit volatile oil to rat small intestine inflammatory factor
As shown in Figure 6, amomum fruit volatile oil can significantly reduce small intestine NF- κ B concentration and proinflammatory factor ROS, TNF-α it is dense
Spend (p<0.001), we have detected MPO contents in small intestine in addition, and VOA can significantly inhibit rat MPO caused by 5-FU
The rise of content, and it is the most obvious with middle dosage effect.As can be seen here, amomum fruit volatile oil can significantly inhibit small intestine caused by 5-FU
The rise of inflammatory factor.
(6) influence that amomum fruit volatile oil is expressed p38MAPK and caspase-3
As shown in Figure 7, amomum fruit volatile oil can significantly inhibit the expression of p38MAPK and caspase-3 in small intestine, and to volatilize
Oily high dose effect is the most notable.As can be seen here, amomum fruit volatile oil can suppress 5-FU induction intestinal mucosal injury rat cell wither
The generation died.
(7) influence of the amomum fruit volatile oil to gut barrier function
Give after 5-FU, model group LPS contents are significantly raised, and amomum fruit volatile oil inhibits LPS liter to a certain extent
Height, at the same time, after 5-FU is given, under model group rats intestinal tight connection albumen ZO-1, occludin expression are obvious
Drop, and amomum fruit volatile oil can significantly reverse this change, and it is more obvious with volatile oil high dose effect.Thus, fructus amomi volatilizees
LPS enters blood caused by oil can suppress 5-FU, increases the expression of tight junction protein, and then improve intestinal mucosal barrier caused by 5-FU
Impaired (Fig. 8).
(8) regulation of the amomum fruit volatile oil to gut flora
Amomum fruit volatile oil can increase the relative abundances such as probiotic lactic acid bacillus, Bifidobacterium, and reduce Escherichia coli, pylorus
The relative abundance of the conditioned pathogens such as helicobacter.Amomum fruit volatile oil can improve by Bacteria from Gl Tract of Rats caused by 5-FU as can be seen here
Imbalance, increase intestine microbial diversity simultaneously maintains its stable state.
In summary, amomum fruit volatile oil can improve body weight, the decline of appetite caused by chemotherapeutic 5-FU, the generation of diarrhoea,
5-FU, which can be suppressed, causes the rise of inflammatory factor, reduces the expression of caspase-3, suppresses LPS and enters blood, increase intestines are close
The expression of albumen is connected, and then improves the damage by intestinal barrier in rats caused by 5-FU.In addition, amomum fruit volatile oil can also lead to
Cross increase beneficial bacteria of intestinal tract to subtract, the relative abundance of few conditioned pathogen improves the imbalance of gut flora caused by 5-FU, maintains intestines
Road Tiny ecosystem relatively stablize.
The preparation of the soft capsule of embodiment 3
Amomum fruit volatile oil is taken, in the soybean oil matrix for adding 1.5 times of amounts, stirring makes it be uniformly dispersed, cross colloid mill, compacting
Into soft capsule, produce, soft capsule shell uses gelatin：Glycerine：Water presses 1:0.5:1 ratio is prepared from.
The preparation of the soft capsule of embodiment 4
Amomum fruit volatile oil is taken, is added in the matrix being made up of the soybean oil and 0.3 times of lecithin measured of 1.2 times of amounts, stirring
It is uniformly dispersed, cross colloid mill, be pressed into soft capsule, produce, soft capsule shell uses gelatin：Glycerine：Water presses 1:0.3:1.2
Ratio is prepared from.
The preparation of the soft capsule of embodiment 5
Amomum fruit volatile oil is taken, in the gelatin substrate for adding 1.5 times of amounts, stirring makes it be uniformly dispersed, and crosses colloid mill, is pressed into
Soft capsule, is produced, and soft capsule shell uses gelatin：Glycerine：Water presses 1.5:0.5:1 ratio is prepared from.
Presently preferred embodiments of the present invention is the foregoing is only, the substantial technological content model of the present invention is not limited to
Enclose, substantial technological content of the invention is broadly to be defined in the right of application, any technology that other people complete
Entity or method, if identical with defined in the right of application, also or a kind of equivalent change, will
It is considered as being covered by among the right.
Claims (9)
1. purposes of the amomum fruit volatile oil in the medicine for alleviating chemotherapy cause intestinal mucosal injury is prepared.
2. purposes of the amomum fruit volatile oil in preparing regulating intestinal canal flora, maintaining the medicine of gut flora balance.
3. purposes according to claim 1 or 2, it is characterised in that the medicine is oral formulations.
4. purposes according to claim 3, it is characterised in that the medicine is soft capsule.
5. the purposes according to claim any one of 1-4, it is characterised in that the preparation method of the amomum fruit volatile oil is：
Choose Yunnan and introduce a fine variety Fructus Amomi (Amomun villosum Lour), precision weighs 100g and is placed in round-bottomed flask after crushing,
Plus distilled water 600ml, half an hour is soaked, using extraction by steam distillation 8h, collects and protected after volatile oil, anhydrous sodium sulfate drying
- 4 DEG C of refrigerators are stored in, are produced.
6. a kind of alleviate the soft capsule that chemotherapy causes intestinal mucosal injury, it is characterised in that it is by active ingredient, matrix and soft capsule
Shell is constituted, and the active ingredient is amomum fruit volatile oil, and the soft capsule shell is by gelatin：Glycerine：Water presses (1-1.5):(0.2-
0.8):The ratio of (1-1.5) is made.
7. soft capsule according to claim 6, it is characterised in that the preparation method of the amomum fruit volatile oil is：Choose
Fructus Amomi (Amomun villosum Lour) is introduced a fine variety in Yunnan, and precision weighs 100g and is placed in round-bottomed flask after crushing, plus is steamed
Distilled water 600ml, soaks half an hour, using extraction by steam distillation 8h, collects and preserved after volatile oil, anhydrous sodium sulfate drying
In -4 DEG C of refrigerators, produce.
8. soft capsule according to claim 6, it is characterised in that the matrix includes soybean oil, beeswax, gelatin, ovum
One or more in phosphatide.
9. the preparation method of soft capsule according to claim 6, it is characterised in that its preparation process is：Fructus amomi is waved
Hair oil is added in matrix, and stirring makes it be uniformly dispersed, and is crossed colloid mill, is pressed into soft capsule, produces.
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| CN201710224798.1A CN106943564B (en) | 2017-04-07 | 2017-04-07 | Fructus amomi volatile oil soft capsule for relieving intestinal mucosa injury caused by chemotherapy |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113318085A (en) * | 2021-06-07 | 2021-08-31 | 云南中医药大学 | Fructus amomi tablet for improving vomiting of pregnancy reaction and preparation method thereof |
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| CN101439083A (en) * | 2007-11-19 | 2009-05-27 | 北京亚东生物制药有限公司 | Chinese medicine soft capsules for clearing wind heat and clearing nasal passage, as well as preparation method and quality control method |
| CN105169203A (en) * | 2015-09-25 | 2015-12-23 | 云南中医学院 | Fructus amomi extract and application thereof |
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2017
- 2017-04-07 CN CN201710224798.1A patent/CN106943564B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101439083A (en) * | 2007-11-19 | 2009-05-27 | 北京亚东生物制药有限公司 | Chinese medicine soft capsules for clearing wind heat and clearing nasal passage, as well as preparation method and quality control method |
| CN105169203A (en) * | 2015-09-25 | 2015-12-23 | 云南中医学院 | Fructus amomi extract and application thereof |
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| CN113318085A (en) * | 2021-06-07 | 2021-08-31 | 云南中医药大学 | Fructus amomi tablet for improving vomiting of pregnancy reaction and preparation method thereof |
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