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CN117531000A - New use of Ginseng radix constitution consolidating oral liquid in preventing and treating sepsis - Google Patents

New use of Ginseng radix constitution consolidating oral liquid in preventing and treating sepsis Download PDF

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Publication number
CN117531000A
CN117531000A CN202210915155.2A CN202210915155A CN117531000A CN 117531000 A CN117531000 A CN 117531000A CN 202210915155 A CN202210915155 A CN 202210915155A CN 117531000 A CN117531000 A CN 117531000A
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oral liquid
sepsis
ginseng
mice
building
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李市荣
姚景春
王会萍
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Shandong New Time Pharmaceutical Co Ltd
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Shandong New Time Pharmaceutical Co Ltd
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    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/65Paeoniaceae (Peony family), e.g. Chinese peony
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    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/80Scrophulariaceae (Figwort family)
    • A61K36/804Rehmannia
    • AHUMAN NECESSITIES
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/884Alismataceae (Water-plantain family)
    • AHUMAN NECESSITIES
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/894Dioscoreaceae (Yam family)
    • A61K36/8945Dioscorea, e.g. yam, Chinese yam or water yam
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    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/896Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A61K36/8965Asparagus, e.g. garden asparagus or asparagus fern
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Abstract

The invention belongs to the field of medicines, and relates to a new application of ginseng body-building oral liquid, in particular to a new application of ginseng body-building oral liquid in preventing and treating sepsis. The research result of the prevention and treatment effect of the ginseng body-building oral liquid on sepsis model mice by singly using or combining vancomycin shows that: the ginseng body-building oral liquid can improve the general state of sepsis mice, increase the body mass, reduce the death rate of sepsis mice, restore the reduced white blood cell number and the increased neutrophil percentage to be normal, and reduce the increased levels of TNF-alpha, IL-1 beta and IL-6 of sepsis patients by singly using or combining vancomycin. Compared with the conventional antibiotics, the ginseng body-building oral liquid has the advantages of difficult generation of drug resistance and no toxic or side effect, and has important clinical significance for treating sepsis.

Description

New use of Ginseng radix constitution consolidating oral liquid in preventing and treating sepsis
Technical Field
The invention belongs to the field of medicines, and relates to a new application of ginseng body-building oral liquid, in particular to a new application of ginseng body-building oral liquid in preventing and treating sepsis.
Background
Sepsis is a common complication following severe trauma, severe infection, burns and major surgery, manifesting as systemic inflammatory response syndrome (systemic inflammatory response syndrome, SIRS), possibly further leading to multiple organ dysfunction syndrome and circulatory failure. Sepsis has the characteristics of high incidence, rapid development, high mortality rate, high treatment cost and the like. Sepsis pathogenesis is mainly in that infection causes massive release of inflammatory mediators, further activating various cells and multiple organ systems throughout the body, ultimately leading to serious consequences.
Sepsis has been identified in 2017 as a global health-first event, with its morbidity and mortality remaining high, severely threatening human life health. With the aging of population, the increase of newborns, the increase of antibiotic resistant strains, the increase of immunodeficiency patients, the increase of infection acquired in communities and hospitals and the like, the problem of sepsis needs to be solved.
The ginseng body-building oral liquid is an exclusive product of Lunan Sanpu pharmaceutical Co Ltd, and the approval document is 'national medicine standard character Z10940013', is prepared from ginseng, rehmannia root, poria cocos, tree peony bark, prepared rehmannia root, dogwood, chinese yam, rhizoma alismatis, radix asparagi and dwarf lilyturf tuber, and has the effects of nourishing yin, tonifying qi and building up body. Can be used for treating cough due to deficiency of yin and qi, palpitation, short breath, hectic fever, soreness of waist, tinnitus, spermatorrhea, night sweat, and dry stool. In the intensive research and secondary development process of the ginseng body-building oral liquid, the inventor creatively combines the antibiotics and the ginseng body-building oral liquid for treating the sepsis, proves that the combination of the antibiotics and the ginseng body-building oral liquid has a synergistic curative effect on the sepsis, can reduce the generation of side effects, and is suitable for popularization and use in clinic. The prior art has no report on the use of the ginseng body-building oral liquid for treating the sepsis, and has no report on the use of the ginseng body-building oral liquid and antibiotics in combination for treating the sepsis.
Disclosure of Invention
In order to solve the problem of sepsis caused by infection, the invention provides a pharmaceutical composition for treating sepsis. The technical scheme of the invention is as follows:
a pharmaceutical composition for treating sepsis consists of ginseng solid-base oral liquid and antibiotics.
In the intensive research and secondary development process of the ginseng body-building oral liquid, the inventor creatively combines the antibiotics and the ginseng body-building oral liquid for treating the sepsis, proves that the combination of the antibiotics and the ginseng body-building oral liquid has a synergistic curative effect on the sepsis, can reduce the generation of side effects, and is suitable for popularization and use in clinic.
The invention also provides a combined medicine for treating sepsis, which is a combined medicine consisting of the ginseng body-building oral liquid and antibiotics which are simultaneously administered.
Further, the ginseng body-strengthening oral liquid is prepared from ginseng, rehmannia root, prepared rehmannia root, dogwood, yam, moutan bark, alisma orientale, poria cocos, radix asparagi and dwarf lilyturf tuber.
Further, the antibiotic is selected from vancomycin.
Further, the volume-mass ratio of the ginseng body-building oral liquid to the antibiotics is as follows: mass (v: m) =2: 12.5-4:12.5 (l: g).
Further, the volume-mass ratio of the ginseng body-building oral liquid to the antibiotics is as follows: mass (v: m) =4: 12.5 (l: g).
The invention also provides application of the ginseng body-building oral liquid and antibiotics serving as active ingredients in preparing medicines for treating sepsis.
In the embodiment of the invention, the ginseng body-building oral liquid and vancomycin are given to sepsis model mice, the difference of various indexes of each group of mice is observed, and the prevention and treatment effects of the ginseng body-building oral liquid and the vancomycin on sepsis are examined, so that the following findings are obtained:
the ginseng body-building oral liquid and vancomycin can play a synergistic role in improving general conditions and inflammatory symptoms of sepsis patients, not only can obviously improve general conditions of sepsis mice and increase body mass and reduce mortality of the sepsis mice, but also can better improve pathological conditions compared with the ginseng body-building oral liquid or vancomycin which is singly used, can restore the reduced white blood cell number and the increased neutrophil percentage to be normal, reduces the increased levels of TNF-alpha, IL-1 beta and IL-6 of the sepsis patients, and has a synergistic therapeutic effect on sepsis.
The ginseng body-building oral liquid and vancomycin have the following advantages when being used for treating sepsis:
1. has remarkable effect
The ginseng body-building oral liquid and vancomycin have remarkable effects of improving general conditions and inflammatory symptoms of sepsis patients, are superior to the use of vancomycin alone, are also superior to the use of ginseng body-building oral liquid alone, and have very important significance on survival prognosis of sepsis patients when combined administration.
2. Mild action and no toxic side effect
The ginseng body-building oral liquid has the advantages of mild effect, comprehensive conditioning effect on human body, less possibility of drug resistance and no toxic or side effect compared with the conventional antibiotics and hormone medicines. The combined administration can reduce the dosage and the administration period of the conventional antibiotics, thereby reducing the side effects of the antibiotics.
The foregoing description is merely an overview of the technical aspects of the present invention, and is intended to be illustrative of the embodiments of the present invention in order to make it possible to clearly understand the technical means of the present invention and to implement the present invention in accordance with the contents of the specification.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
The following further illustrates the inventive content of the present invention by means of specific examples, but it should be understood that the inventive examples are not in any way limiting.
Example prevention and treatment effects of Ginseng radix Guben oral liquid and vancomycin on sepsis mice
1. Experimental method
1.1 Experimental grouping
Female Balb/c mice, total body mass (25+ -2) g, were randomly divided into normal control group, model group, vancomycin group, ginseng radix Guben oral liquid group, joint 1 group, joint 2 group, joint 3 group and joint 4 group.
1.2 modeling and packet administration
The mice of each group are fasted and water-forbidden for 12 hours before operation, after being anesthetized by adopting the ranazine and the sultai 50, the abdominal midline is cut for about 1cm, the cecum is free, the tail end ligation is carried out, and a 16-gauge needle is used for puncturing and extruding a little excrement at the 0.5cm position of the tail end of the cecum, and then the mice are sutured. Normal control mice were opened only without ligating the cecum.
Before and on the day of molding, vancomycin (12.5 mg/kg) was administered by tail intravenous injection, the ginseng-to-solid oral liquid group was administered by stomach infusion (4 ml/kg), the combined administration group was administered by stomach infusion with the same volume of physiological saline as that of the normal control group and the model group except for tail intravenous injection. The doses and modes of administration for each group were as follows:
vancomycin group: 12.5mg/kg of vancomycin is administered by intravenous injection;
ginseng radix is used for consolidating constitution: the ginseng body-building oral liquid is administrated by stomach irrigation with 4ml/kg;
combination 1 group: intravenous injection of vancomycin 12.5mg/kg and oral liquid 1ml/kg of the stomach-perfusing ginseng root-strengthening oral liquid;
in combination with group 2: intravenous injection of vancomycin 12.5mg/kg and 2ml/kg of oral liquid of the stomach-perfusing ginseng root;
combination of 3 groups: intravenous injection of vancomycin 12.5mg/kg and oral liquid of lavage ginseng for consolidating constitution 4ml/kg;
in combination with 4 groups: 12.5mg/kg of vancomycin and 6ml/kg of ginseng root-fixing oral liquid for stomach irrigation are injected intravenously.
2. Detection index
2.1 general Condition observations
The following indices were examined and recorded post-operatively: respiratory rate, mental state, behavioral activity, animal mass, and death.
2.2 Biochemical index detection
After molding for 48 hours, the mice were sampled via the orbit and placed into a tube with anticoagulant, mixed well, and the white blood cell count (white blood cell coun, WBC) and neutrophil percentage (neutrophil percentage, NE%) indicators were counted with a cytometer. After centrifugation of 1200g of the remaining blood, the upper plasma was taken and the IL-6, TNF-. Alpha.and IL-1β levels in the plasma were measured according to ELISA kit instructions.
3. Statistical treatment
All data were statistically processed using GraphPad Prism 5.0 toIndicating whether the overall data is different or not by single factor analysis of varianceIf the difference exists, the significance test is carried out by using a t test method, and the difference is statistically significant with p < 0.05.
4. Experimental results and discussion
4.1 changes in general signs, physical quality and mortality in mice
The quality of the normal control group mice is slightly reduced after molding, the quality of the 1 st d body is gradually recovered to 26.5g, the normal activity is achieved, the hair color is normal, and no death occurs; the mice in the model group showed a marked decrease in body mass in 1d after model building, showing listlessness, hair erection, shortness of breath, reduced activity, and difficulty in feeding water. There was a different reduction in mortality in each of the dosing groups compared to the model group. Compared with vancomycin and ginseng root-strengthening oral liquid for single use, mortality of mice in 1-4 groups after operation for 24 hours, 48 hours and 72 hours is obviously reduced, weight recovery trend is obvious, most activities are normal, hair color is normal, activities are reduced only individually, hair is vertical, and abnormal feeding and water intake occur. Mortality was lowest in the combination 3 groups, followed by the combination 2 groups. As the dose increased, mortality of mice in group 4 in combination increased slightly compared to group 3 in combination. The oral liquid for strengthening body resistance and the vancomycin are combined for use, so that the prognosis of sepsis can be improved, and the death rate can be reduced. The body mass change and death of each group of mice are shown in Table 1 and Table 2 respectively:
table 1 average body constitution change of mice in each group
Table 2 comparison of death status of mice in each group
4.2 expression level of inflammation index in mice of each group
The percentages of white blood cells and neutrophils for each group of mice are shown in Table 3. Compared with the normal control group, the white blood cell number of the mice in the model group is obviously reduced, the percentage of neutrophils is obviously increased, and the difference is statistically significant (p < 0.01); compared with the model group, the white blood cell number of each administration group of mice is obviously increased, the percentage of neutrophils is obviously reduced except the ginseng body-building oral liquid group, and the difference compared with the model group has statistical significance (p <0.05, p < 0.01); compared with vancomycin group and ginseng body-building oral liquid group, the combination 1-4 groups have obvious differences (p <0.05, p < 0.01) in increasing the white blood cell number of mice and reducing the percentage of neutrophils, and the combination 3 groups have optimal effect, and the combination 2 groups are the next.
The above results indicate that: the ginseng body-building oral liquid and vancomycin can obviously increase the white blood cell number of the sepsis mice, reduce the neutrophil percentage of the sepsis mice, and have synergistic prevention and treatment effects on the sepsis mice.
Table 3 percentage comparison of white blood cells and neutrophils from each group of mice
In comparison with the normal control group, # p<0.05, ## p<0.01;
in contrast to the set of models, $ p<0.05, $$ p<0.01;
in contrast to the vancomycin group, * p<0.05, ** p<0.01;
compared with the ginseng body-building oral liquid, p<0.05, %% p<0.01。
comparison of inflammatory factor levels in mice of each group as shown in Table 4, the serum levels of TNF- α, IL-1β and IL-6 were significantly increased in the model group compared to the normal control group, and the differences were statistically significant (p < 0.05); the levels of TNF-alpha, IL-1 beta and IL-6 were significantly reduced (p <0.05, p < 0.01) in the serum of vancomycin and mice from groups 1-4 compared to the model group, were statistically significant compared to the model group, and were most significant in the 3 groups.
Table 4 comparison of inflammatory factors in mice of each group
Group of TNF-α(ng/ml) IL-1β(ng/ml) IL-6(ng/ml)
Normal control group 10.01±3.5 29.42±5.51 6.65±2.82
Model group 139.69±29.68 ## 558.02±63.2 ## 51.73±1.88 ##
Vancomycin group 78.86±13.14 $ 407.56±56.9 $ 40.17±5.39 $$
Ginseng oral liquid group for strengthening body resistance 95.82±6.90 $ 464.69±78.3 46.11±4.25
Combination of group 1 77.98±15.26 $$ 441.26±37.85 $$ 40.76±5.02 $
Combination of 2 groups 64.47±8.65 $$*%% 348.68±36.31 $$*%% 33.63±4.89 $$*%%
Combination of 3 groups 59.58±9.88 $$**%% 320.31±65.21 $$*%% 27.06±12.61 $$*%%
Combination of 4 groups 71.22±6.77 $$%% 371.22±62.51 $$% 38.06±5.67 $$%
In comparison with the normal control group, # p<0.05, ## p<0.01;
in contrast to the set of models, $ p<0.05, $$ p<0.01;
in combination with vancomycinThe ratio of the two components is that, * p<0.05, ** p<0.01;
compared with the ginseng body-building oral liquid, p<0.05, %% p<0.01。
the experimental results show that: (1) The ginseng body-building oral liquid and vancomycin combined have obvious improvement effect on the recovery of the quality of the sepsis mice, and compared with the single-use ginseng body-building oral liquid and the single-use vancomycin, the ginseng body-building oral liquid and the single-use vancomycin can obviously reduce the death rate of the mice. (2) Compared with the single-use ginseng body-building oral liquid and the single-use vancomycin, the combination of the ginseng body-building oral liquid and the vancomycin can obviously reduce the serum inflammatory factor level of the sepsis mice, improve the inflammatory state of the sepsis mice, and have a synergistic effect on the sepsis when being used in combination.

Claims (10)

1. A pharmaceutical composition for treating sepsis is characterized by comprising ginseng solid oral liquid and antibiotics.
2. The use according to claim 1, wherein the volume-to-mass ratio of the ginseng solid oral liquid to the antibiotics is: mass = 2:12.5-4:12.5.
3. the use according to claim 2, wherein the volume-to-mass ratio of the ginseng solid oral liquid to the antibiotics is: mass=4: 12.5.
4. a pharmaceutical composition according to any one of claims 1 to 3, wherein the antibiotic is selected from vancomycin.
5. The combined medicine for treating sepsis is characterized in that the combined medicine is a combined medicine of ginseng body-building oral liquid and antibiotics which are simultaneously administered.
6. The combination according to claim 5, wherein the volume-to-mass ratio of the ginseng solid oral liquid to the antibiotic is: mass = 2:12.5-4:12.5.
7. the combination according to claim 6, wherein the volume-to-mass ratio of the ginseng solid oral liquid to the antibiotic is: mass=4: 12.5.
8. the combination according to any one of claims 5 to 7, wherein the antibiotic is selected from vancomycin.
9. The ginseng body-building oral liquid and antibiotics are simultaneously used as active ingredients and are used for preparing medicines for treating sepsis.
10. The use according to claim 9, wherein the volume to mass ratio of the ginseng solid oral liquid to the antibiotics is: mass = 2:12.5-4:12.5.
CN202210915155.2A 2022-08-01 2022-08-01 New use of Ginseng radix constitution consolidating oral liquid in preventing and treating sepsis Pending CN117531000A (en)

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