CN114569590A - Medical application of sodium new houttuyfonate - Google Patents
Medical application of sodium new houttuyfonate Download PDFInfo
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- CN114569590A CN114569590A CN202210384916.6A CN202210384916A CN114569590A CN 114569590 A CN114569590 A CN 114569590A CN 202210384916 A CN202210384916 A CN 202210384916A CN 114569590 A CN114569590 A CN 114569590A
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- sodium
- new houttuyfonate
- sodium new
- colon cancer
- snh
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- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
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- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
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- QJQRNDGUWQVAEV-AAFSJPGBSA-M sodium bisulfite adduct Chemical compound [Na+].[O-]S(=O)(=O)C([C@H]1N(C(C2=C3)=O)C=C(C1)/C=C/C(=O)N(C)C)NC2=CC1=C3OCO1 QJQRNDGUWQVAEV-AAFSJPGBSA-M 0.000 description 1
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- HPPWMWCITPGPKK-UHFFFAOYSA-M sodium;1-hydroxy-3-oxododecane-1-sulfonate Chemical compound [Na+].CCCCCCCCCC(=O)CC(O)S([O-])(=O)=O HPPWMWCITPGPKK-UHFFFAOYSA-M 0.000 description 1
- UAJTZZNRJCKXJN-UHFFFAOYSA-M sodium;2-dodecoxy-2-oxoethanesulfonate Chemical compound [Na+].CCCCCCCCCCCCOC(=O)CS([O-])(=O)=O UAJTZZNRJCKXJN-UHFFFAOYSA-M 0.000 description 1
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Images
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the field of pharmacy, in particular to a pharmaceutical application of sodium new houttuyfonate. The new houttuynin sodium can be used for preparing medicines for inhibiting Fusobacterium nucleatum.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to a new application of sodium new houttuyfonate.
Background
With the development of omics technology, the occurrence and development processes of various diseases are closely related to the infection of fusobacterium nucleatum. Fusobacterium nucleatum (Fn) is the highest-content Fusobacterium in the oral cavity of human beings, and often causes various opportunistic infections. Clinical studies show that fusobacterium nucleatum not only causes oral diseases, but also plays an important role in diseases such as poor pregnancy outcome and tumors. A large amount of fusobacterium nucleatum is separated from clinical specimens of various diseases such as colon cancer, osteomyelitis, pericarditis, brain abscess and the like. The current studies indicate that fusobacterium nucleatum adhesion proteins FadA and Fap2 can induce and promote the occurrence and development of inflammatory bowel disease and colon cancer. The method mainly shows that high abundance fusobacterium nucleatum is related to poor prognosis of patients; ② the recurrence of cancer may be partly due to the ability of F.nucleatum to promote resistance of colon cancer tissues to chemotherapy.
Colon cancer (CRC) is the second leading cause of cancer-related death worldwide, and its prevalence is escalating in individuals under the age of 50, particularly. CRC is a heterogeneous disease of the intestinal epithelium and is characterized by accumulation of mutations and dysregulation of the immune response. There is increasing evidence that up to 90% of the risk of disease is due to environmental factors such as diet, consistent with recent literature reports of CRC-related "carcinogenic flora". However, unlike the well-known causal role of H.pylori in gastric cancer, no specific microorganism has been identified to date that triggers CRC. Therefore, it is necessary to decipher the specific pathogenic flora or metabolites driving CRC and characterize its underlying mechanisms.
Houttuynia cordata is fresh whole plant or dried aerial parts of Houttuynia cordata of Saururaceae, Houttuynia cordiata Thunb, and is recorded in miscellaneous records of famous physicians. The houttuynin is derived from volatile oil of herba Houttuyniae, and is unstable and easily degradable. The sodium bisulfite addition compound sodium new houttuyfonate is commonly used clinically at present. The Sodium New Houttuyfonate (SNH) has obvious antibacterial effect and obvious inhibition effect on staphylococcus aureus, escherichia coli, sporothrix and the like. Is an antibacterial and anti-inflammatory medicament clinically.
Disclosure of Invention
The invention aims to provide a new application of sodium new houttuyfonate.
Specifically, the invention provides an application of sodium new houttuyfonate in preparing a medicament for inhibiting fusobacterium nucleatum.
In a preferred embodiment, the sodium new houttuyfonate is used as the only active ingredient for preparing the medicament for inhibiting the fusobacterium nucleatum.
In another preferred embodiment, the drug for inhibiting fusobacterium nucleatum can be used for treating colon cancer.
The details of various aspects of the invention are set forth in subsequent sections. The features, objects, and advantages of the invention will be apparent from the description and from the claims.
Drawings
FIG. 1: the MIC method measures the inhibitory effect of SNH on Fn.
FIGS. 2a to 2c show the effect of SNH on colon cancer and normal cell growth by the CCK-8 method.
Wherein: panels a, b, c show the effect of SNH on colon cancer HCT116, colon cancer HT29 and colon epithelial cell growth, respectively.
FIG. 3a to FIG. 3d show the inhibitory effect of SNH on the proliferation of colon cancer cells by Fusobacterium nucleatum.
Wherein: FIG. a is the total effect of SNH on Colon cancer cell proliferation by Fusobacterium nucleatum; and (b), c and d are respectively shown in different time periods of 24h, 48h and 72h for detecting the inhibitory effect of SNH on the colon cancer cell proliferation of fusobacterium nucleatum.
FIGS. 4 a-4 c SNH significantly inhibited the growth of colon cancer tumors in Fn-infected nude mice.
Wherein: FIG. a shows the sizes of colon cancer tumors in nude mice in a control group, an SNH administration group and a positive control group; panel b is colon cancer tumor weight in each group of nude mice; panel c is colon cancer tumor volume in groups of nude mice.
FIG. 5 demonstrates enrichment of Fn in colon cancer tumor tissue in nude mice by RT-PCR in this model.
Detailed Description
The chemical name of Sodium New Houttuyfonate (SNH) of the invention is: sodium bisulfite adduct of lauroyl acetaldehyde, molecular formula C14H27NaO5S, relative molecular weight 330.41, and structural formula:
the Sodium New Houttuyfonate (SNH) of the present invention can be purchased commercially. The purity of the product meets the pharmaceutical standard. The purity of Sodium New Houttuyfonate (SNH) is best > 98%.
Take the case of preparing the Sodium New Houttuyfonate (SNH) into a medicament. The Sodium New Houttuyfonate (SNH) of the present invention may be used alone or in the form of a pharmaceutical composition. The pharmaceutical composition comprises the Sodium New Houttuyfonate (SNH) as a main active ingredient and a pharmaceutically acceptable carrier. Generally, the pharmaceutical composition of the present invention should contain 0.1 to 99.9% by weight of the active natural ingredient Sodium New Houttuyfonate (SNH) of the present invention. The pharmaceutically acceptable carrier does not destroy the pharmaceutical activity of the Sodium New Houttuyfonate (SNH) of the invention; meanwhile, the effective dosage of the composition can play a role of the drug carrier without toxic and harmful effects on human bodies.
Such pharmaceutically acceptable carriers include, but are not limited to: lecithin, aluminum stearate, alumina, ion exchange materials, self-emulsifying drug delivery systems, tweens or other surfactants, serum proteins, buffer substances such as phosphates, glycine, sorbic acid, water, salts, electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, magnesium silicate, mixtures of saturated fatty acid partial glycerides, and the like.
Other conventional pharmaceutical adjuvants such as binder (such as microcrystalline cellulose), filler (such as starch, glucose, anhydrous lactose and lactose beads), disintegrant (such as crosslinked PVP, crosslinked sodium carboxymethyl starch, crosslinked sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose), absorption enhancer, adsorbent carrier, flavoring agent, sweetener, excipient, diluent, and wetting agent.
The Sodium New Houttuyfonate (SNH) and pharmaceutical compositions thereof of the present invention may be prepared according to conventional methods in the art and administered by the gastrointestinal route. The oral preparation comprises capsules, tablets, oral liquid, granules, pills and the like. Therefore, the route of administration of the Sodium New Houttuyfonate (SNH) and the pharmaceutical composition thereof of the present invention should be selected from oral delivery routes.
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.
The features mentioned above with reference to the invention, or the features mentioned with reference to the embodiments, can be combined arbitrarily. All the features disclosed in this specification may be combined in any combination, and each feature disclosed in this specification may be replaced by alternative features serving the same, equivalent or similar purpose. Thus, unless expressly stated otherwise, the features disclosed are merely generic examples of equivalent or similar features.
Antibacterial activity detection after experiment of sodium new houttuyfonate acting on Fn
The experimental method comprises the following steps: and detecting the minimum inhibitory concentration of the traditional Chinese medicine monomer to the fusobacterium nucleatum according to a micro-double dilution method. Adjusting the concentration of the bacterial liquid to 10 by using a Mach turbidimetry method8CFU/mL, adding traditional Chinese medicine monomer sodium new houttuyfonate into the test group, adding liquid culture medium without traditional Chinese medicine monomer sodium new houttuyfonate into the blank control group, adding 0.1% DMSO into the solvent group as blank control, fully mixing each group with 3 repeat holes in a volume of 1:1 with the prepared Fusobacterium nucleatum liquid, and culturing in an incubator at 37 ℃. Determining OD600 value by using a full-wavelength microplate reader to determine MIC value of the traditional Chinese medicine monomer. The experiment was repeated 3 times.
The experimental results are as follows: the minimum bactericidal concentration is the minimum concentration required to kill bacteria. The assay was performed by passage to agar plates without drug using the broth dilution minimum inhibitory concentration assay. And (3) after culturing for 18-24h at 37 ℃, observing the growth condition of bacteria, wherein the aseptic growth is the minimum bactericidal concentration of the tested medicine. As shown in fig. 1, MIC of sodium new houttuyfonate was measured by a 2-fold serial dilution method. The results show that: the sodium new houttuyfonate has strong antibacterial activity, and the MIC of the sodium new houttuyfonate is 200 mu M.
Experimental detection of proliferation toxicity of sodium bishouttuyfonate on colon cancer cells and colon epithelial cells
The experimental method comprises the following steps: HCT-116, HT29 and 460 cells were observed and when the cell density reached 90%, the cells were digested with 0.25% pancreatin. The digested cells were cell counted and seeded into 96-well plates with 5000 HCT-116 cells per well. After the cells adhere to the wall, adding culture media of sodium new houttuyfonate with different concentrations into a 96-well plate, and setting 6 repeated groups in each group. Cell viability was measured at 24h, 48h, 72h respectively, medium was removed before measurement and 10. mu.L of CCK-8 test solution was added to each well. Setting a blank hole (only adding the detection solution), incubating for 1-2h at 37 ℃, detecting the absorbance of 450nm by using a microplate reader, and repeating the experiment for 3 times.
The experimental results are as follows: as shown in FIGS. 2a to 2c, the CCK8 experiment shows that after SNH intervention, SNH has little influence on cell activity at an effective dose (200. mu.M) with antibacterial activity, and most colon cancer cells and colon epithelial cells can grow normally.
Experiment detection of inhibition effect of sodium trineohouttuyfonate on Fn-infected colon cancer cells
The experimental method comprises the following steps: for cell proliferation assays, resuspension of HCT-116 cells was performed at 1X 10 per well4Inoculate in 24-well plates and add 2mL of complete medium. Cells were incubated with multiples of Fn infection and given different concentrations of the drug, metronidazole treated cells were used as positive controls. Cell counts were performed using a Counstar cytometer at 24 hours, 48 hours, and 72 hours. Each experiment was repeated 3 times.
The experimental results are as follows: as shown in fig. 3a to fig. 3d, cell counting experiments show that fusobacterium nucleatum can significantly promote proliferation of colon cancer cells, the proliferation level of the cells is significantly reduced after the sodium new houttuyfonate is used for pretreatment, and the longer the time is, the stronger the inhibition effect of the sodium new houttuyfonate is.
After experiment of colon cancer model mice infected by Fn under action of sodium houttuyfonate, tumor growth condition detection
The experimental method comprises the following steps: nude mice were purchased from Shanghai Slek animal experiment center, and the experiment was started after 1 week of normal adaptive feeding; reviving human colon cancer cell HCT-116, subculturing to the third generation, digesting the cell with trypsin, centrifuging, collecting, washing twice with PBS, and suspending to obtain single cell suspension. The preparation was injected subcutaneously into nude mice with a micro-syringe. Visible to the naked eye after day 6 of inoculationThe tumor nodules of (a) and (b) were measured using a vernier caliper with the formula v being 0.5x (axb)2) Tumor volume was calculated. Tumors were measured every 3 days. 0.9% NaC1 and Fn were injected in a laminar flow super clean bench at multiple points around the tumor with sterile microsyringes, starting on day 9 of inoculation, in a total volume of 100. mu.L per tumor every 3 days; and a sterile microinjector was used to inject 0.9% NaCl into the abdominal cavity, the total volume of the injection being 100. mu.L per nude mouse. The total injection is carried out for 6 times, the tumor weight is measured by an electronic analytical balance on the 2 nd day after the last injection, and a digital single-lens reflective view-finding camera is used for taking a picture. The tumor tissue was stored in a freezer at-80 ℃.
The experimental results are as follows: as shown in fig. 4a to fig. 4c and fig. 5, the fusobacterium nucleatum can obviously promote the growth of the tumor of the colon cancer mouse, when the sodium new houttuyfonate acts on the Fn-infected colon cancer model mouse, the growth of the tumor cell in the mouse is obviously inhibited, and after the tumor is taken out, the tumor is obviously reduced compared with the model group, which indicates that the growth of the tumor is inhibited.
Various aspects of the invention are set forth above. It should be understood, however, that equivalent changes and modifications may be made thereto by those skilled in the art without departing from the spirit of the invention, and such changes and modifications are intended to fall within the scope of the appended claims of this application.
Claims (3)
1. Application of sodium new houttuyfonate in preparing medicine for inhibiting Fusobacterium nucleatum is provided.
2. Use according to claim 1, characterized in that the sodium new houttuyfonate is used as the sole active ingredient in the preparation of a medicament for inhibiting fusobacterium nucleatum.
3. Use according to claim 1, characterized in that the said medicament inhibiting fusobacterium nucleatum is useful for the treatment of colon cancer.
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