CN106943564B - Fructus amomi volatile oil soft capsule for relieving intestinal mucosa injury caused by chemotherapy - Google Patents

Fructus amomi volatile oil soft capsule for relieving intestinal mucosa injury caused by chemotherapy Download PDF

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CN106943564B
CN106943564B CN201710224798.1A CN201710224798A CN106943564B CN 106943564 B CN106943564 B CN 106943564B CN 201710224798 A CN201710224798 A CN 201710224798A CN 106943564 B CN106943564 B CN 106943564B
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volatile oil
fructus amomi
soft capsule
intestinal mucosa
chemotherapy
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CN106943564A (en
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俞捷
顾雯
赵荣华
毛晓健
杨兴鑫
张婷
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Yunnan University of Traditional Chinese Medicine TCM
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
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    • A61K36/88—Liliopsida (monocotyledons)
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    • A61K36/9064—Amomum, e.g. round cardamom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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 or decoction

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Abstract

The invention relates to a fructus amomi volatile oil soft capsule for relieving intestinal mucosa injury caused by chemotherapy, and provides application of the fructus amomi volatile oil in preparing a medicament for relieving the intestinal mucosa injury caused by the chemotherapy, and also provides a soft capsule for relieving the intestinal mucosa injury caused by the chemotherapy and a preparation method thereof.

Description

Fructus amomi volatile oil soft capsule for relieving intestinal mucosa injury caused by chemotherapy
Technical Field
The invention relates to the field of medicinal preparations, in particular to a fructus amomi volatile oil soft capsule for relieving intestinal mucosa injury caused by chemotherapy.
Background
Chemotherapy plays an important role in the treatment of malignant tumors, but chemotherapeutic drugs have a toxic effect on normal cells while killing tumor cells. Investigation shows that after receiving repeated chemotherapy, the intestinal barrier function of a tumor patient is seriously damaged, on one hand, the effective absorption area of intestinal mucosa is reduced, and nutrient substance malabsorption and bleeding, diarrhea, pain and the like with different degrees are caused; on the other hand, intestinal permeability is increased, flora in intestinal cavities is displaced, immunity of patients is reduced, and infection rate and death rate are increased. Therefore, the improvement of the intestinal mucosa damage caused by chemotherapy and the related gastrointestinal adverse reaction is an urgent social need.
Amomum villosum (Amomi fruits) is one of four southern medicines in China, and has the medicinal and edible history of more than 1300 years. Fructus amomi is a perennial herb of the genus cardamomum in the family zingiberaceae, has warm property and pungent taste, has the effects of resolving dampness, stimulating appetite, warming spleen, checking diarrhea, regulating qi, preventing miscarriage and the like, and is a common medicine for treating gastrointestinal diseases in traditional Chinese medicine. Modern pharmacological research shows that the main effective components in the fructus amomi comprise volatile substances such as borneol acetate, camphor, limonene, borneol and the like, and have the effects of improving gastrointestinal functions, relieving pain, stopping diarrhea, promoting secretion of digestive juice, regulating intestinal flora and the like. The long-term clinical practice and modern research of fructus amomi as a common medicinal and edible medicinal material show that the medicinal material has the advantages of small toxic and side effect and obvious medicinal effect.
The existing medicines for treating intestinal mucosa injury caused by chemotherapy have very limited treatment effects and different effects. Therefore, it is urgently desired to obtain a drug for treating intestinal mucosa injury after chemotherapy, which has an excellent effect.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a medicament for treating intestinal mucosa injury after chemotherapy, which has excellent effect. The inventor discovers that the fructus amomi volatile oil has excellent effect of relieving intestinal mucosa injury caused by chemotherapy through research, so the invention provides the following technical scheme for solving the technical problem:
the application of the fructus amomi volatile oil in preparing the medicine for relieving intestinal mucosa injury caused by chemotherapy and the application of the fructus amomi volatile oil in preparing the medicine for adjusting intestinal flora and maintaining the balance of the intestinal flora is common oral preparations in the field, and the medicine is preferably soft capsules.
The invention also provides a soft capsule for relieving intestinal mucosa injury caused by chemotherapy and a preparation method thereof, the soft capsule consists of an effective component, a matrix and a soft capsule shell, the effective component is the amomum fruit volatile oil, and the soft capsule shell is prepared from gelatin: glycerol: the water is prepared according to the proportion of (1-1.5) to (0.2-0.8) to (1-1.5). The matrix comprises one or more of soybean oil, beeswax, gelatin and lecithin.
The preparation method of the soft capsule for relieving intestinal mucosa injury caused by chemotherapy comprises the following steps: adding fructus Amomi volatile oil into matrix, stirring to disperse uniformly, grinding with colloid mill, and making into soft capsule.
The fructus amomi volatile oil used in the invention can be prepared by adopting fructus amomi volatile oil which is conventionally used in the field, or can be prepared by selecting Yunnan seed introduction fructus amomi (Amomun villosum L our), crushing, precisely weighing 100g, placing in a round bottom flask, adding 600ml of distilled water, soaking for half an hour, extracting for 8 hours by adopting a steam distillation method, collecting the volatile oil, drying with anhydrous sodium sulfate, and storing in a refrigerator at the temperature of-4 ℃.
The invention has the beneficial effects that:
the fructus amomi volatile oil can improve the weight and appetite reduction and diarrhea caused by chemotherapeutic drugs 5-FU, can inhibit the increase of inflammatory factors caused by 5-FU, reduce the expression of apoptosis protease, inhibit L PS from entering blood, increase the expression of intestinal tight junction protein, and further improve the damage of rat intestinal mucosa barrier caused by 5-FU.
Drawings
FIG. 1 shows the effect of the volatile oil of Amomum villosum on the body weight and food intake of rats in each group.
FIG. 2 shows a photograph of the rectum of each group of rats.
FIG. 3 shows small intestine physiological sections (× 10-fold) of rats in each group.
Figure 4 shows the rat small intestinal villus height/crypt depth (note: p <0.05, # p <0.01, # p <0.001 compared to the normal group, # p <0.05, # p <0.01, # p <0.001 compared to the model group).
FIG. 5 shows the effect of Amomum villosum essential oil on blood I L-6 and ROS in rats (Note: p <0.05, # p <0.01, # p <0.001 in the normal group, # p <0.05, # p <0.01, # p <0.001 in the model group).
FIG. 6 shows the effect of Amomum villosum essential oil on rat small intestine ROS, TNF- α, MPO, NF- κ B (Note: p <0.05, # p <0.01, # p <0.001 compared to normal group, # p <0.05, # p <0.01, # p <0.001 compared to model group).
FIG. 7 shows the effect of Amomum villosum essential oil on rat p38MAPK, caspase-3 (Note: p <0.05, # p <0.01, # p <0.001 in comparison to the normal group, # p <0.05, # p <0.01, # p <0.001 in comparison to the model group).
FIG. 8 shows the effect of Amomum villosum essential oil on rat enterotoxin L PS, Claudin ZO-1, occludin (Note: p <0.05, # p <0.01, # p <0.001 compared to the normal group, # p <0.05, # p <0.01, # p <0.001 compared to the model group).
Fig. 9 shows the relative abundance of gut microbes at the family and genus levels.
Detailed Description
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out according to conventional conditions or according to conditions recommended by the manufacturers. All percentages, ratios, proportions, or parts are by weight unless otherwise specified.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, any methods and materials similar or equivalent to those described herein can be used in the methods of the present invention. The preferred embodiments and materials described herein are intended to be exemplary only.
EXAMPLE 1 preparation of Amomum villosum volatile oil
Selecting Yunnan seed of fructus Amomi (Amomun villosum L our), pulverizing, precisely weighing 100g, placing in round bottom flask, adding distilled water 600ml, soaking for half an hour, extracting by steam distillation for 8 hr, collecting volatile oil, drying with anhydrous sodium sulfate, and storing in refrigerator at-4 deg.C.
Example 2 protective action of Amomum villosum volatile oil on 5-FU-induced intestinal mucosa injury of rat
Preparation and administration mode of intestinal mucosa injury model
48 experimental SD rats are respectively provided with a normal group (CON), a model group (MOD), a positive drug gold bifidobacterium group (CB L, 450mg/kg), a fructus amomi volatile oil low dose group (VOA. L, 8mg/kg), a fructus amomi volatile oil medium dose group (VOA.M, 16mg/kg), and a fructus amomi volatile oil high dose group (VOA.H, 32mg/kg), except the normal group, the chemotherapy time of other groups of rats is 5 days, 35mg/kg of intraperitoneal injection of 5 fluorouracil (5-FU) is carried out every day, 4 hours before chemotherapy, treatment drugs are given to each group for fasting lavage, the equal volume of physiological saline for lavage of the stomach of the normal group and the model group is 12 days, the weight and the food intake of the rats are recorded during the experiment, and the experimental animal death of the rat diarrhea condition is observed on the 12 th day.
At the end of the experiment, blood is collected from the canthus veins in the eyes, centrifuged at 10000r.min-1 at 4 ℃ for 15min, and blood serum is taken to detect the I L-6 and ROS content.
After the experiment is finished, anesthetizing a rat by chloral hydrate solution, using a disposable vacuum venous blood collection tube, collecting hepatic portal vein blood, centrifuging for 10min at 2000r.min < -1 >, collecting upper layer plasma, detecting the content of enterogenic endotoxin (L PS) by using a limulus reagent, fixing the small intestine 1cm close to 10cm away from the pylorus in 10% formalin solution for 24h, carrying out pathological section detection, cutting a rectum part, photographing for observing the diarrhea condition of the rat, collecting part of the small intestine, washing off intestinal lysate by PBS, cutting and weighing 2g of crushed small intestine, adding 2ml of PBS into a glass homogenizing tube for manual homogenization, centrifuging for 10min at 4 ℃ under 4000r.min < -1 >, collecting supernatant, and detecting the expression of inflammatory factors (ROS, NF-kappa B, TNF- α), related proteases (MPO, p38MAPK, pascae-3) and zon (ZO-1, ocludin) in the small intestine cells after twice repeated freeze thawing and cracking.
(II) the influence of the fructus Amomi volatile oil on the weight, appetite and diarrhea of rats
As shown in figure 1, the fructus amomi volatile oil can effectively reverse the reduction of the body weight and the food intake of rats caused by 5-FU, and the effect is most remarkable when the volatile oil is used in a high-dose mode. Meanwhile, as shown in the proctogram of FIG. 2, after 5-FU was administered, severe diarrhea occurred in rats in the model group, while significantly formed feces were observed in the normal group and each treatment group, suggesting that the fructus Amomi volatile oil can prevent the occurrence of diarrhea in rats caused by 5-FU.
(III) Effect of Amomum villosum volatile oil on histopathological changes of rat intestinal mucosa
As shown in FIG. 3, the small intestine mucosa of the rats in the model group was significantly atrophic, part of villi was exfoliated and shortened, epithelial cells were denatured and necrotic, and crypts were increased after the administration of 5-FU, compared to the normal group, and the lesions in the small intestine were significantly reversed in each treatment group after the administration. Similarly, it can be shown by the crypt ratio that each treatment group can obviously resist the phenomenon of the rat small intestine villus reduction induced by 5-FU (figure 4), and the amomum fruit volatile oil component presents a certain dosage relation.
(IV) Effect of Amomum villosum volatile oil on rat blood inflammatory factor
As shown in figure 5, the fructus amomi volatile oil can obviously reduce the concentration of proinflammatory factors I L-6 and ROS in blood, and has obvious effect at high dose.
(V) Effect of fructus Amomi volatile oil on rat Small intestine inflammatory factor
As shown in figure 6, the fructus amomi volatile oil can obviously reduce the concentration of NF-kB in small intestine and the concentrations of proinflammatory factors ROS and TNF- α (p is less than 0.001), and in addition, the content of MPO in small intestine tissues is detected, VOA can obviously inhibit the increase of MPO content in rats caused by 5-FU, and the effect is most obvious in medium dosage.
(VI) Effect of Amomum villosum essential oil on p38MAPK and caspase-3 expression
As shown in figure 7, the fructus amomi volatile oil can obviously inhibit the expression of p38MAPK and caspase-3 in small intestine, and the effect is most obvious when the volatile oil is used in high dosage. Therefore, the fructus amomi volatile oil can inhibit the generation of apoptosis of rat cells with intestinal mucosa injury induced by 5-FU.
Influence of (seven) fructus amomi volatile oil on intestinal mucosa barrier function
After 5-FU is given, the content of L PS in the model group is obviously increased, while the amomum villosum volatile oil inhibits the increase of L PS to a certain extent, meanwhile, after 5-FU is given, the expression of ZO-1 and occludin in the intestinal tract of a rat in the model group is obviously reduced, and the amomum villosum volatile oil can obviously reverse the change and has an obvious effect by using high dose of volatile oil, so that the amomum villosum volatile oil can inhibit L PS caused by 5-FU from entering blood, increase the expression of the occludin, and further improve the damage of the intestinal mucosa barrier caused by 5-FU (figure 8).
(Ba) regulation of intestinal flora by fructus Amomi volatile oil
The fructus amomi volatile oil can increase the relative abundance of probiotics, such as lactobacillus, bifidobacterium and the like, and reduce the relative abundance of conditional pathogenic bacteria, such as escherichia coli, helicobacter pylori and the like. Therefore, the fructus amomi volatile oil can improve the imbalance of rat intestinal flora caused by 5-FU, increase the diversity of intestinal microorganisms and maintain the steady state of the intestinal microorganisms.
In conclusion, the fructus amomi volatile oil can improve the weight and food intake reduction and diarrhea caused by chemotherapeutic drugs 5-FU, can inhibit the increase of inflammatory factors caused by 5-FU, can reduce the expression of apoptosis protease, can inhibit L PS from entering blood, can increase the expression of intestinal tight junction protein, and further can improve the damage of rat intestinal mucosa barrier caused by 5-FU.
EXAMPLE 3 preparation of Soft capsules
Adding fructus Amomi volatile oil into 1.5 times of soybean oil matrix, stirring to disperse uniformly, grinding with colloid mill, and making into soft capsule with gelatin as shell: glycerol: the water is prepared according to the proportion of 1:0.5: 1.
EXAMPLE 4 preparation of Soft capsules
Adding fructus Amomi volatile oil into matrix composed of 1.2 times of soybean oil and 0.3 times of lecithin, stirring to disperse uniformly, grinding with colloid mill, and making into soft capsule with gelatin: glycerol: the water is prepared according to the proportion of 1:0.3: 1.2.
EXAMPLE 5 preparation of Soft capsules
Adding fructus Amomi volatile oil into 1.5 times of gelatin matrix, stirring to disperse uniformly, grinding with colloid mill, and making into soft capsule with gelatin as shell: glycerol: the water is prepared according to the proportion of 1.5:0.5: 1.
The foregoing is merely a preferred embodiment of the invention and is not intended to limit the scope of the invention, which is defined by the claims appended hereto, and any other technical entity or method that is encompassed by the claims as broadly defined herein, or equivalent variations thereof, is contemplated as being encompassed by the claims.

Claims (1)

1. Use of fructus Amomi volatile oil soft capsule in preparing medicine for improving intestinal flora imbalance and intestinal mucosa barrier damage caused by 5-FU;
the preparation method of the fructus amomi volatile oil comprises the following steps: selecting Yunnan seed, introducing fructus Amomi, pulverizing, precisely weighing 100g, placing in round bottom flask, adding distilled water 600ml, soaking for half an hour, extracting by steam distillation for 8 hr, collecting volatile oil, drying with anhydrous sodium sulfate, and storing in refrigerator at-4 deg.C;
the preparation method of the soft capsule comprises the following steps: adding fructus Amomi volatile oil into 1.5 times of gelatin matrix, stirring to disperse uniformly, grinding with colloid mill, and making into soft capsule with gelatin as shell: glycerol: the water is prepared according to the proportion of 1.5:0.5: 1.
CN201710224798.1A 2017-04-07 2017-04-07 Fructus amomi volatile oil soft capsule for relieving intestinal mucosa injury caused by chemotherapy Expired - Fee Related CN106943564B (en)

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Citations (2)

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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
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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
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赵锦."海南砂仁挥发油对实验性溃疡性结肠炎的作用及其安全性评价".《中国优秀硕士论文电子期刊网》.2009,第10-11、17、34-37页. *

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