CN116585417B - Traditional Chinese medicine compound composition for treating sepsis and preparation method and application thereof - Google Patents
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- 230000009466 transformation Effects 0.000 description 1
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Classifications
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Abstract
The invention belongs to the field of traditional Chinese medicines, and relates to a traditional Chinese medicine compound composition for treating sepsis, and a preparation method and application thereof. The traditional Chinese medicine compound composition comprises the following components in parts by weight: 25-35 parts of cornu bubali, 20-25 parts of radix rehmanniae, 10-15 parts of radix paeoniae rubra, 5-10 parts of cortex moutan, 2-6 parts of coptis chinensis, 5-10 parts of radix ophiopogonis, 2-5 parts of radix scrophulariae, 10-15 parts of rheum officinale and 5-10 parts of raw liquorice. The Chinese herbal compound composition can relieve the IL-6, TNF-alpha and other inflammatory mediator levels of sepsis model mice, relieve sepsis inflammatory storm, and improve prognosis. The traditional Chinese medicine compound composition can relieve liver cell degeneration, alveolar interstitial exudation and renal fibrosis of a sepsis model mouse, and protect organ functions and tissue multi-organ dysfunction syndrome.
Description
Technical Field
The invention belongs to the field of traditional Chinese medicines, and relates to a traditional Chinese medicine compound composition for treating sepsis, and a preparation method and application thereof.
Background
Sepsis is a life-threatening organ dysfunction caused by a deregulation of the body's response to infection. Recent global epidemiological surveys have shown that sepsis mortality rates of 26.7% -41.9%, up to 13.4 billion dollars/year of treatment cost, place a heavy burden on society and home. Cytokine storm (cytokine release syndrome, CRS) activates systemic inflammatory response inducing immune imbalance, a major cause of poor sepsis prognosis. Inhibiting early CRS, maintaining immune homeostasis, is an important therapeutic direction for sepsis. 2021 "rescue sepsis exercise: international guidelines for treatment "fail to provide effective strategies. Focusing the leading field of sepsis immune responses, the pathogenesis of CRS was explored deeply in a new perspective, driving the clinical transformation of sepsis immunotherapy, and being urgent.
The current primary technical means for alleviating the systemic inflammatory response of sepsis is Continuous Renal Replacement (CRRT) therapy. The main disadvantages of this method include: (1) Deep vein catheters are needed to be placed, and related complications have high incidence rate, such as catheter infection, deep vein thrombosis and the like; (2) CRRT-related complications are more, such as bleeding and thrombosis induced by improper anticoagulation, infection, disorder of water electrolyte and acid-base balance, severe anemia, shock, etc.; (3) invasive procedures increase patient pain; (4) the treatment cost is high.
The traditional Chinese medicine is used as one of common treatment methods for sepsis, and is matched with the conventional comprehensive treatment of sepsis such as liquid management, anti-infection, mechanical ventilation, nutrition support and the like, so that the traditional Chinese medicine not only can reduce the systemic inflammatory response of organisms, but also can regulate and control the coagulation state of organisms, enhance the immune function and improve prognosis. Therefore, the development of the traditional Chinese medicine compound composition for treating sepsis has important significance.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides the traditional Chinese medicine compound composition for treating sepsis, which can obviously reduce the systemic inflammatory response of sepsis, regulate and control the coagulation state, strengthen the immune function and improve the prognosis.
The invention also solves the technical problem of providing a preparation method of the traditional Chinese medicine compound composition.
Further, the technical problem to be solved by the invention is to provide the application of the traditional Chinese medicine compound composition in preparing medicines for treating sepsis.
In order to solve the technical problems, the invention adopts the following technical scheme:
the invention discloses a traditional Chinese medicine compound composition for treating sepsis, which comprises the following components in parts by weight:
25-35 parts of buffalo horn,
20-25 parts of radix rehmanniae,
10 to 15 parts of radix paeoniae rubra,
5 to 10 parts of cortex moutan,
2 to 6 parts of coptis chinensis,
5 to 10 parts of dwarf lilyturf tuber,
2-5 parts of radix scrophulariae,
10 to 15 parts of rhubarb,
5-10 parts of raw licorice.
Preferably, the traditional Chinese medicine compound composition comprises the following components in parts by weight:
30 parts of buffalo horn, and the like,
24 parts of radix rehmanniae recen,
12 parts of radix paeoniae rubra,
9 parts of cortex moutan,
4 parts of coptis chinensis,
6 parts of dwarf lilyturf tuber,
4 parts of radix scrophulariae, which are mixed together,
12 parts of rheum officinale,
6 parts of raw licorice.
In some embodiments, the formulation of the traditional Chinese medicine compound composition is an extract, a granule, a tablet, a capsule or a liquid preparation.
The traditional Chinese medicine compound composition is also within the protection scope of the invention.
The invention also discloses a preparation method of the traditional Chinese medicine compound composition, which comprises the steps of mixing cornu bubali with water, and firstly decocting with strong fire for 20-40 minutes to obtain cornu bubali liquid medicine; soaking radix rehmanniae, radix paeoniae rubra, cortex moutan, coptis chinensis, dwarf lilyturf tuber, figwort root and raw liquorice in water, adding cornu bubali liquid medicine after the soaking is finished, boiling for 10-20 minutes with strong fire, decocting for 30-50 minutes with slow fire, adding rheum officinale, decocting for 5-10 minutes with slow fire, and filtering after the decoction is finished to obtain liquid medicine A and filter residues; adding water into the filter residue, boiling for 10-20 minutes with strong fire, decocting for 15-25 minutes with slow fire, and filtering after the decoction is finished to obtain liquid medicine B; combining the liquid medicine A and the liquid medicine B, and concentrating to obtain concentrated solution.
In some embodiments, the buffalo horn is mixed with water in a mass to volume ratio of 1g:6 to 10mL, preferably 1g:8mL; the weight-volume ratio of the total weight of the dried rehmannia root, the red peony root, the cortex moutan, the coptis chinensis, the dwarf lilyturf tuber, the figwort root and the raw liquorice to the water is 1g:6 to 10mL, preferably 1g:8mL, soaking time is 40-80 minutes, preferably 60 minutes.
In some embodiments, the filter residue is added with water, and the mass volume ratio of the filter residue to the water is 1g: 4-8 mL, preferably 1g:6mL.
In some embodiments, the concentration is performed at 100-120 ℃ until the relative density of the concentrated solution is 2.10-2.18 g/mL; preferably, the concentration is at 110℃to a relative density of 2.14g/mL.
In some embodiments, pharmaceutically acceptable excipients are added to the concentrate during the preparation process.
The application of the traditional Chinese medicine compound composition in preparing the medicine for treating sepsis is also within the protection scope of the invention.
The traditional Chinese medicine compatibility principle of the traditional Chinese medicine compound composition provided by the invention is as follows:
sepsis is a life-threatening organ dysfunction caused by infection reaction disorder, and according to the pathological mechanisms of systemic inflammatory reaction, coagulation dysfunction, oxidative stress, immune disorder and the like in sepsis, by combining with the theory of traditional Chinese medicine symptoms, the traditional Chinese medicine symptoms of sepsis are summarized into heat toxin symptoms, blood stasis symptoms, viscera qi obstruction symptoms and acute deficiency symptoms, a treatment method of bacterial toxin simultaneous treatment is provided for the traditional Chinese medicine to treat sepsis, wherein the heat toxin symptoms are the initial stage of sepsis, pathogenic heat invasion, and vital qi beat, cross and do not solve, enter the lung to dryness, enter the heart to disturb the mind, enter the spleen to traumas, enter the liver to wind, enter the kidney to fire, internal vexation of five viscera, body fluid to large injury, qi and blood deficiency symptoms, and bone skin and skin of tendons are not dependent on, and form and endanger, so the early cut-off toxic heat symptoms are serious in preventing the sepsis from being transmitted and worsened, by the following: heat is retained in the interior, and is bitter with salty and cold nature, and with sweet and bitter nature, and with acid. The traditional Chinese medicine compound composition disclosed by the invention is added and modified by adding formulas such as buffalo horn rehmannia decoction, liquid increasing decoction, heart-purging decoction and the like, and takes the effects of clearing heat and detoxicating, cooling blood and benefiting yin as a fundamental treatment method, and the buffalo horn bitter, salty, sour and cold, and the effects of clearing heart-fire, cooling blood and detoxifying are taken as monarch drugs; the dried rehmannia root is sweet, bitter and cold, is ministerial, and has the functions of clearing heat and cooling blood, assisting the monarch to clear heat in blood and restoring injured yin; radix paeoniae rubra and cortex moutan Xin Han are used for enabling heat to gather and dissipate, enhancing the blood cooling capacity, promoting blood circulation and preventing the disadvantage of blood stasis, radix scrophulariae and radix ophiopogonis are slightly added, radix rehmanniae is used for taking the sense of augmentation, assisting blood heat and recovering yin liquid, coptis is bitter and cold and clearing away heart fire, preventing heat from being transmitted back to pericardium, rheum officinale bitter and cold is used for enhancing the effect of clearing heat by distributing cornu bubali, radix paeoniae rubra and cortex moutan are used for enhancing the effect of promoting blood circulation, radix rehmanniae, radix scrophulariae and radix ophiopogonis are used for protecting yin liquid, flaming up, causing qi to be reversed, rheum officinale to be downwards and promoting qi to function, the six ingredients are used as adjuvants, liquorice is sweet and flat, and has effects of tonifying qi, purging fire and harmonizing medicines. The syndrome of excessive heat toxin in the initial stage of sepsis is completely fastened, the heat toxin in qi and blood is directly cleared, and the characteristics of excessive heat, blood movement, dryness and body fluid impairment and the like are considered, and the medicine has the functions of promoting blood circulation, increasing fluid Gu Yin, reinforcing the middle-jiao, dissipating the middle-jiao and relieving the pathogenic heat to strengthen qi.
The beneficial effects are that:
(1) The traditional Chinese medicine compound composition for relieving the systemic inflammatory response of sepsis adopts scientific proportion, and all the components can be mutually coordinated and promoted to play a role in synergy. Traditional Chinese medicine considers that when sepsis is caused, pathogenic qi is sudden and excessive, healthy qi is not deficient, healthy qi and pathogenic factors struggle, pathogenic heat is excessive, and the disease enters into the house to be combined with blood and blood heat, turbid yin liquid is decocted to form blood stasis, blood stasis and heat are combined with each other, dirty qi is fatigued, and 27538 is a danger for rapid life. In the traditional Chinese medicine treatment, when the Chinese medicine compound composition takes strengthening body resistance to eliminate pathogenic factors as a treatment rule, the Chinese medicine compound composition has the effects of clearing heat and detoxicating, tonifying qi and nourishing yin, and has the effect of relieving the systemic inflammatory response of sepsis, and animal experiments have definite efficacy, and after the Chinese medicine compound composition is prepared into a standardized Chinese medicine preparation, the standardized treatment of the Chinese medicine in the sepsis field can be promoted.
(2) The Chinese herbal compound composition can relieve the IL-6, TNF-alpha and other inflammatory mediator levels of sepsis model mice, relieve sepsis inflammatory storm, prevent immune imbalance and improve prognosis.
(3) The traditional Chinese medicine compound composition can relieve myocardial cell injury, alveolar interstitial exudation, hepatocyte degeneration, renal fibrosis and small intestine structural damage of a sepsis model mouse, protect organ functions and prevent the occurrence of multiple organ dysfunction syndrome.
Drawings
The foregoing and/or other advantages of the invention will become more apparent from the following detailed description of the invention when taken in conjunction with the accompanying drawings and detailed description.
FIG. 1 is a graph of the base peak ion flow chromatogram of a traditional Chinese medicine compound composition and the total ion flow chromatogram of a mixed reference solution; wherein, fig. 1 (a) is a basic peak ion flow chromatogram (BPC) of the traditional Chinese medicine compound composition in a negative ion mode, fig. 1 (B) is a basic peak ion flow chromatogram (BPC) of the traditional Chinese medicine compound composition in a positive ion mode, fig. 1 (C) is a total ion flow chromatogram (TIC) of the mixed reference substance solution in a negative ion mode, and fig. 1 (D) is a total ion flow chromatogram (TIC) of the mixed reference substance solution in a positive ion mode.
FIG. 2 shows LC-MS data of chemical components (No. 1-20) in the Chinese herbal medicine compound composition.
FIG. 3 shows LC-MS data of chemical components (No. 21-44) in the compound Chinese medicinal composition.
FIG. 4 shows LC-MS data of chemical components (No. 45-67) in the compound Chinese medicinal composition.
FIG. 5 shows LC-MS data of chemical components (No. 68-89) in the compound Chinese medicinal composition.
FIG. 6 shows LC-MS data of chemical components (No. 90-108) in the compound Chinese medicinal composition.
Fig. 7 shows the effect of the compound traditional Chinese medicine composition on the general state of mice.
Fig. 8 is the effect of the herbal compound composition on the weight of mice.
Fig. 9 shows the effect of the compound Chinese medicinal composition on the heart, lung, liver, kidney and small intestine of mice.
FIG. 10 shows the effect of a herbal compound composition on inflammatory factors in mice; wherein, # # P < 0.0001 compared to the blank; p < 0.001 and P < 0.0001 compared to model group.
FIG. 11 shows the effect of a herbal compound composition on mouse macrophages; wherein, # # P < 0.0001 compared to the blank; p < 0.01 compared to model group.
Detailed Description
The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials, unless otherwise specified, are commercially available.
The drug used in the modeling of the embodiment of the invention is lipopolysaccharide, abbreviated as LPS.
Example 1
A traditional Chinese medicine compound composition for treating sepsis comprises the following components in parts by weight: 30 parts of cornu bubali, 24 parts of radix rehmanniae, 12 parts of radix paeoniae rubra, 9 parts of cortex moutan, 4 parts of coptis chinensis, 6 parts of radix ophiopogonis, 4 parts of radix scrophulariae, 12 parts of rheum officinale and 6 parts of raw liquorice.
The preparation method comprises the following steps: mixing cornu Bubali with water (the mass volume ratio of cornu Bubali to water is 1g:8 mL), and decocting with strong fire for 30min to obtain cornu Bubali liquid medicine; soaking radix rehmanniae, radix Paeoniae Rubra, cortex moutan, coptidis rhizoma, radix Ophiopogonis, radix scrophulariae and Glycyrrhrizae radix in water (the total weight of radix rehmanniae, radix Paeoniae Rubra, cortex moutan, coptidis rhizoma, radix Ophiopogonis, radix scrophulariae and Glycyrrhrizae radix and water are 1g:8 mL) for 60 min, adding cornu Bubali liquid medicine after soaking, boiling with strong fire for 15 min, decocting with slow fire for 40 min, adding radix et rhizoma Rhei, decocting with slow fire for 5min, and filtering with 8 layers of gauze to obtain liquid medicine A and residue; adding water into the filter residue (the mass volume ratio of the filter residue to the water is 1g:6 mL), boiling with strong fire for 15 minutes, decocting with slow fire for 20 minutes, and filtering with 8 layers of gauze after the decoction is finished to obtain liquid medicine B; combining the liquid medicine A and the liquid medicine B, concentrating at 110 ℃ until the relative density of the concentrated solution is 2.14g/mL, and obtaining the concentrated solution, namely the liquid preparation of the Chinese herbal compound composition; preserving at 4 ℃ for standby.
Example 2: high resolution mass spectrum analysis of chemical components in traditional Chinese medicine compound composition
(1) Instrument for measuring and controlling the intensity of light
AB SCIEX Triple TOFTM 5600 mass spectrometer (AB Sciex Co., USA), LC-20A rapid liquid phase spectrometer (Shimadzu Co., japan), milli-Q ultra pure water machine (Millipore Co., USA), speed Vac centrifugal concentrator (Thermo Scientific Co., USA), ER-2000A rotary evaporator (Shanghai Asia Biochemical instruments).
(2) Reagent(s)
Acetonitrile, methanol (chromatographic purity, merck, germany), formic acid (chromatographic purity, ala Ding Shiji, inc.), ethanol (analytical purity, south-Beijing chemical agents, inc.), pure water (laboratory homemade).
Gallic acid (lot number: 18032703), coptisine hydrochloride (lot number: 20021903), epiberberine (lot number: 19081404), palmatine (lot number: 18022602) and jateorhizine hydrochloride (lot number: 19083006) were purchased from duprifid biotechnology limited; harpagoside (lot number: RFS-H02101908013), harpagoside (lot number: RFS-H02001911019) berberine (lot number: RFS-X04501904009) and chrysophanol (lot number: RFS-D01711811012) were purchased from Chengdoreminispide Biotechnology Co., ltd; protocatechuic acid (lot number: RFS-Y03111812016) was purchased from Chengdoremifos Biotechnology Co., ltd; ellagic acid (lot number: PS0845-0020 MG) was purchased from Chengdu Poisson Biotech Co., ltd; glycyrrhizin (111610-201005) and ammonium glycyrrhizate (lot number: 110731-202021) are all purchased from Chinese food and drug administration institute; all the reference substances are of a grade for content measurement, and the purity is more than 98%.
(3) High performance liquid chromatography conditions:
chromatographic column: thermo AcclaimTM RSLC 120C18 column (3.0 mm. Times.100 mm,2.2 μm);
column temperature: 40 ℃;
mobile phase a:0.1% formic acid water (v/v);
mobile phase B: acetonitrile;
flow rate: 0.3mL/min;
sample injection amount: 3 μL;
gradient elution procedure: 0-3 min,10% mobile phase B; 3-20 min, 10-25% of mobile phase B; 20-30 min, 25-40% mobile phase B; 30-41 min, 40-60% of mobile phase B; 41-55 min, 60-85% of mobile phase B; 55-58 min, 85-95% mobile phase B; 58.1-63 min, 95-100% of mobile phase B; and stopping for 63.1 min.
(4) Mass spectrometry conditions:
electrospray ion source (ESI);
ion source Temperature (TEM) 550 ℃;
curtain air (CUR) 40psi;
atomizing gas (GS 1) 55psi;
auxiliary heating gas (GS 2) 55psi;
ion source spray voltage (IS) 5500V/-5500V;
collision voltage (CE) 40V/-40V;
the declustering voltage (DP) is 100V/-100V;
the scanning range is between 50 and 1500 m/z.
(5) Preparation of a mixed control solution: taking 10-20 mg of 13 reference substances in the reagent (2) respectively, dissolving the reference substances with methanol by ultrasonic waves (40 ℃ C., 60Hz, 5 min) respectively, and then fixing the volume into a 25mL volumetric flask, and uniformly mixing to prepare stock solutions of the reference substances. And precisely transferring each reference substance solution into a volumetric flask with 1-50 mL, adding methanol to dilute to a scale, and uniformly mixing by ultrasound (at 40 ℃ and 60Hz for 5 min) to prepare a mixed reference substance solution with the concentration of each reference substance of 8-16 mug/mL, wherein the mixed reference substance solution is used for liquid chromatography-mass spectrometry analysis of the subsequent mixed reference substance solution.
(6) And (3) data processing: firstly, referring to relevant literature data at home and abroad, attributing chemical component information contained in the traditional Chinese medicine compound composition according to medicinal materials, and establishing a compound library; information on chemical formula or molecular weight etc. was then imported into Peakview SoftwareTM (AB Sciex) software for data analysis. And comparing and referencing fragment information provided by the secondary mass spectrum with information reported by a reference substance, a compound database and related documents, and further confirming chemical components and structures of the compounds in the traditional Chinese medicine compound composition. The data derived in Peakview was mapped using Origin Pro 8.0.
Example 3: sepsis mice rearing and modeling
(1) Sepsis mice feeding conditions: 41 male C57 mice are purchased from An Nuokang biological company, the body mass is 18-20 g, the mice are fed into the common environment of animal houses in hospitals in Jiangsu province, the temperature is 20-25 ℃, the relative humidity is 55-65%, artificial illumination and dark time are 12h alternately, free feeding and drinking are realized, 1 padding is replaced every three days, and the mice are suitable for starting experiments after 3 days of feeding.
(2) Modeling and administration of animals: the 41C 57 mice were randomly divided into a blank group, a model group, a buffalo horn and rehmannia decoction group, a high-dose group and a low-dose group of the traditional Chinese medicine compound composition, wherein 8 mice of the blank group, the buffalo horn and rehmannia decoction group, the high-dose group and the low-dose group of the traditional Chinese medicine compound composition are respectively, and 9 mice of the model group are respectively.
Wherein, the blank group is filled with normal saline; model group intraperitoneal injection of LPS (15 mL kg) -1 ) Pouring normal saline into stomach after 0.5 h; LPS (15 mL kg) -1 ) After 0.5h, the decoction of cornu Bubali and rehmanniae is prepared by decocting to obtain decoction, diluting with purified water, and concentrating to give decoction with concentration of 5g.kg -1 ) The method comprises the steps of carrying out a first treatment on the surface of the High-dose group and low-dose group of traditional Chinese medicine compound composition intraperitoneal injection of LPS (15 mL-kg) -1 ) After 0.5h, the liquid preparation of the gastric lavage Chinese herbal compound composition (prepared in example 1, diluted with purified water, the high dose group concentration of the Chinese herbal compound composition is 10g.kg) -1 The concentration of the low-dose group of the traditional Chinese medicine compound composition is 5 g.kg -1 Converted from clinical dose); the gastric lavage volumes are all 10 mL/kg -1 Then the stomach is irrigated once every 12 hours, and the stomach is irrigated continuously for 60 hours.
Example 4: mouse observation index
(1) General state observation and physical quality and mortality measurement: during the molding and administration period, the weight and death of the mice are monitored in the whole course, the weight is weighed every 12 hours, and a curve is recorded and drawn.
(2) Pathological observations of mice heart, lung, liver, kidney, small intestine: after the experiment, the eyeballs of the mice were bled, and the hearts, lungs, livers, kidneys and small intestines of the mice were taken and fixed in formaldehyde fixation solution. Conventional fixation, paraffin embedding, sectioning, and staining with hematoxylin-eosin (HE) were used. Histopathological assessment is performed by a qualified pathologist.
(3) ELISA method for determining the content of IL-6 and TNF-alpha in mouse serum: the content of IL-6 and TNF-alpha in the serum of the mice is measured by ELISA method according to the instruction of the kit.
(4) Flow cytometry detection of effects on mouse macrophages: 3 mice were taken from each group, and the peritoneal macrophages were stained with FACS solution, stained with F4/80+, CD163+, CD206+ antibodies, and checked on the machine under sterile conditions.
Example 5: experimental results
(1) Analysis of compound Chinese medicine composition material spectrum
Under the condition of UPLC-Q-TOF/MS in the above example 2, 108 chemical components are identified in total, wherein the chemical components comprise 28 saponins, 16 alkaloids, 9 organic acids, 8 iridoid glycosides, 10 anthraquinones, 11 flavonoids, 9 isoflavones, 1 flavonoid, 1 phenethyl alcohol glycoside, 1 limonin, 1 phenylpropionic acid, 4 phenols, 1 glycosides, 1 coumarin, 1 saccharide and 6 other components. Of these, 13 compounds (labeled compounds in fig. 2 to 6 were confirmed by reference) were further confirmed by comparison with the retention time and cleavage fragments of the mixed reference solution, and the remaining compounds were confirmed by investigation of the references in combination with mass spectrometry fragmentation patterns of the respective compounds.
The basic peak ion flow chromatogram of the Chinese medicinal compound composition and the total ion flow chromatogram of the mixed reference substance solution are shown in figure 1; wherein, fig. 1 (a) is a basic peak ion flow chromatogram (BPC) of the traditional Chinese medicine compound composition in a negative ion mode, fig. 1 (B) is a basic peak ion flow chromatogram (BPC) of the traditional Chinese medicine compound composition in a positive ion mode, fig. 1 (C) is a total ion flow chromatogram (TIC) of the mixed reference substance solution in a negative ion mode, and fig. 1 (D) is a total ion flow chromatogram (TIC) of the mixed reference substance solution in a positive ion mode.
Fig. 2 to 6 show LC-MS data of chemical components (No. 1 to 108) in the compound Chinese herbal composition.
(2) The Chinese medicinal compound composition can improve sepsis state of mice
(i) The experimental results show that the mortality of each group of mice is 0.
(ii) As can be seen from fig. 7, the mice in the blank group had smooth hair and good mental status; after the mice of the model group are injected with LPS in the abdominal cavity, the mice have the phenomena of hair frying, loose stool, happiness, listlessness and the like; after the mice are subjected to the gastric lavage of the liquid preparation of the traditional Chinese medicine compound composition for a period of time, the general state of the mice is recovered to different degrees, and the high-dose group is superior to the buffalo horn rehmannia decoction group and the low-dose group.
(iii) As can be seen from fig. 8, the initial body weight of the mice in the blank group was 19.14±0.90, and the body weight after 60 hours was 19.63±1.00, which showed an overall trend of increasing; the initial weight of the mice in the model group is 19.10+/-0.99, and the weight of the mice after 60 hours is 15.34+/-1.75, so that the mice generally have a descending trend; the initial weight of the buffalo horn and rehmannia decoction group mice is 19.10+/-0.86, and the weight of the mice after 60 hours is 15.31 +/-0.87, so that the mice generally have a descending trend; the initial weight of the low-dose group of the traditional Chinese medicine compound composition is 19.13+/-1.00, and the weight after 60 hours is 15.68+/-0.95, and the total weight of the traditional Chinese medicine compound composition is in a descending trend; the initial weight of the high-dose group of the traditional Chinese medicine compound composition is 19.13+/-0.91, the weight after 60 hours is 16.15+/-1.28, the traditional Chinese medicine compound composition firstly has a descending trend, and the traditional Chinese medicine compound composition starts to rise slightly after 48 hours. The buffalo horn and rehmannia decoction is a common prescription for treating sepsis in traditional Chinese medicine, and compared with the buffalo horn and rehmannia decoction, the traditional Chinese medicine compound composition has no obvious difference in mortality rate, but can improve the survival state of mice.
(3) The Chinese medicinal compound composition has effect in protecting viscera
As can be seen from fig. 9, the myocardial fibers of the mice in the model group were arranged in a disordered but discontinuous manner as compared with the blank group; pulmonary interstitial congestion, alveolar edema, hemorrhage, and massive pink inflammatory exudation seen in pulmonary interstitial and alveolar spaces; the liver cells have vacuolation degeneration, cytoplasms shrink, and partial liver lobule normal structure is destroyed; large areas of kidney fibrosis and inflammatory tissue infiltration are visible in the kidneys, the cell shape is absent, and the tubular shape is not obvious; inflammatory cell infiltration exists in intestinal tissues, the pathological structure is seriously damaged, and the hierarchy is unclear.
As can be seen from fig. 9, the mice in the buffalo horn-rehmannia decoction group and the low-dose group of the Chinese herbal compound composition had different degrees of improvement in their respective organs as compared with the model group. Compared with the model group, the myocardial fibers of mice in the high-dose group of the traditional Chinese medicine compound composition are basically orderly and consistent; less alveolar effusion and no obvious abnormality of pulmonary interstitial; the liver cell is basically normal in morphology and the liver lobule is complete in structure; the glomerulus and tubular shape gradually recover; the intestinal tissue structure is basically complete.
(4) The Chinese medicinal composition can relieve inflammatory reaction
As can be seen from fig. 10, the serum IL-6 level of mice in the model group was significantly increased, P < 0.0001, and the difference was statistically significant, compared with the blank group; compared with the model group, the serum IL-6 level of the buffalo horn and rehmannia decoction group and the traditional Chinese medicine compound composition of the low dose and the high dose group is obviously reduced, P is less than 0.0001, and the difference has statistical significance.
As can be seen from fig. 10, the serum TNF- α level of mice in the model group was significantly increased, P < 0.0001, and the difference was statistically significant, compared to the blank group; compared with a model group, the serum TNF-alpha level of the buffalo horn and rehmannia root decoction group, the traditional Chinese medicine compound composition low dose and the high dose group is obviously reduced, wherein the P of the buffalo horn and rehmannia root decoction group and the traditional Chinese medicine compound composition low dose group is less than 0.001, the P of the traditional Chinese medicine compound composition high dose group is less than 0.0001, and the difference has statistical significance.
As can be seen from fig. 11, the average macrophage content in abdominal cavity of mice in the blank group was 78.53%; compared with a blank group, the macrophage content of the mice in the model group is reduced, and the average content is 1.5 percent (P is less than 0.0001); compared with a model group, the macrophage contents of mice in the buffalo horn and rehmannia decoction group and the traditional Chinese medicine compound composition group are increased to different degrees, wherein the average macrophage content of the abdominal cavity of the mice in the buffalo horn and rehmannia decoction group is 10.77 percent (P is more than 0.05, the difference has no statistical significance), the average macrophage content of the abdominal cavity of the mice in the low-dose group is 5.13 percent (P is more than 0.05, the difference has no statistical significance), and the average macrophage content of the abdominal cavity of the mice in the high-dose group is 22.43 percent (P is less than 0.01).
The invention provides a traditional Chinese medicine compound composition for treating sepsis, a preparation method and an application thought and a method thereof, and particularly the method and the way for realizing the technical scheme are numerous, the above is only a preferred embodiment of the invention, and it should be pointed out that a plurality of improvements and modifications can be made to those skilled in the art without departing from the principle of the invention, and the improvements and modifications are also regarded as the protection scope of the invention. The components not explicitly described in this embodiment can be implemented by using the prior art.
Claims (9)
1. A traditional Chinese medicine compound composition for treating sepsis is characterized by being prepared from the following components in parts by weight:
25-35 parts of buffalo horn,
20-25 parts of radix rehmanniae,
10-15 parts of red paeony root medicine,
5-10 parts of cortex moutan,
2-6 parts of coptis chinensis,
5-10 parts of dwarf lilyturf tuber,
2-5 parts of radix scrophulariae,
10-15 parts of rheum officinale,
5-10 parts of raw licorice.
2. The traditional Chinese medicine compound composition according to claim 1, which is characterized by being prepared from the following components in parts by weight:
30 parts of buffalo horn, and the like,
24 parts of radix rehmanniae recen,
12 parts of radix paeoniae rubra,
9 parts of cortex moutan,
4 parts of coptis chinensis,
6 parts of dwarf lilyturf tuber,
4 parts of radix scrophulariae, which are mixed together,
12 parts of rheum officinale,
6 parts of raw licorice.
3. The compound Chinese medicinal composition according to claim 1, wherein the compound Chinese medicinal composition is in the form of an extract, a granule, a tablet, a capsule or a liquid preparation.
4. The method for preparing the traditional Chinese medicine compound composition according to claim 1 or 2, which is characterized in that buffalo horn and water are mixed, and decocted with strong fire for 20-40 minutes to obtain buffalo horn liquid medicine; soaking radix rehmanniae, radix paeoniae rubra, cortex moutan, coptis chinensis, radix ophiopogonis, radix scrophulariae and radix glycyrrhizae in water, adding cornu bubali liquid medicine after soaking, boiling with strong fire for 10-20 minutes, decocting with slow fire for 30-50 minutes, adding rheum officinale, decocting with slow fire for 5-10 minutes, and filtering after decoction is finished to obtain liquid medicine A and filter residues; adding water into the filter residue, boiling for 10-20 minutes with strong fire, decocting with slow fire for 15-25 minutes, and filtering after the decoction is finished to obtain a liquid medicine B; combining the liquid medicine A and the liquid medicine B, and concentrating to obtain concentrated solution.
5. The preparation method of claim 4, wherein the buffalo horn and water are mixed, and the mass-volume ratio of buffalo horn to water is 1g: 6-10 mL; the weight-volume ratio of the total weight of the dried rehmannia root, the red peony root, the cortex moutan, the coptis chinensis, the dwarf lilyturf tuber, the figwort root and the raw liquorice to the water is 1g: 6-10 mL, and the soaking time is 40-80 minutes.
6. The method of claim 4, wherein the filter residue is added with water, and the mass-to-volume ratio of the filter residue to the water is 1g: 4-8 mL.
7. The method according to claim 4, wherein the concentration is performed at 100-120 ℃ until the relative density of the concentrated solution is 2.10-2.18 g/mL.
8. The method according to claim 4, wherein pharmaceutically acceptable excipients are added to the concentrate during the preparation process.
9. Use of a compound Chinese medicinal composition according to claim 1 or 3 in the preparation of a medicament for the treatment of sepsis.
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| 脓毒症中医证候特征及演变规律与导师用药经验的研究;常地;中国优秀硕士学位论文全文数据库 医药卫生科技辑(第7期);E056-834正文第57-60页 * |
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