# US 2014/0193530 A1 · Pharmaceutical composition containing honeysuckle extract and antibiotics, pharmaceutical kit, and use of honeysuckle extract for preparation of drug > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0193530 A1 - Document ID: US20140193530A1 - Status: Published application - Kind: A1 - Application number: 14/238,448 - Filed: 2011-08-12 - Published: 2014-07-10 - Earliest claimed: 2011-08-12 - Assignees: Hankang Biochemical & Pharmaceutical Co., Ltd - Inventors: Tiejun Zhang; Jiangong Shi; Hong Meng; Fengnian Han; Xuwei Ma; Zhulan Li - Web page: https://patentgrep.com/patent/US20140193530A1 ## CPC - A61K 31/7048: having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin} - A61K 31/428: condensed with carbocyclic rings - A61K 31/7042: Compounds having saccharide radicals and heterocyclic rings - A61K 36/355: Lonicera (honeysuckle) - A61P 11/00: Drugs for disorders of the respiratory system - A61P 31/04: Antibacterial agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07H 17/04: Heterocyclic radicals containing only oxygen as ring hetero atoms - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13) - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract Provided is a pharmaceutical composition useful for prevention and/or treatment of diseases caused by bacteria, wherein the pharmaceutical composition comprising a honeysuckle extract containing iridoid compounds and an antibiotic. Also provided is a pharmaceutical kit comprising the honeysuckle extract containing the iridoid compounds and the antibiotics which are separately placed. The honeysuckle extract is used in combination with the antibiotics, the responsiveness of multi-drug resistant bacteria to antibiotics is improved, a clinical application prospect is presented, especially the current status of the refractory bacterial infection diseases caused by the pathogenic bacteria resistant to the antibiotics can be improved. Also provided is a use of the pharmaceutical composition and pharmaceutical kit in the preparation of drugs for prevention and/or treatment a diseases caused by bacteria. In addition, also provided is a use of the honeysuckle extract in the preparation of drugs for reversing bacterial resistance. ## Claims ### Claim at position 1 1-20. (canceled) ### Claim 21 A pharmaceutical composition for preventing and/or treating a disease caused by a bacterium, comprising a honeysuckle extract containing iridoid compounds and an antibiotic; wherein the honeysuckle extract contains secologanic acid represented by the following structural formula (1): wherein in formula (1), X1 and X2 each independently represent O, and R represents H. ### Claim 22 (depends on 21) The pharmaceutical composition according to claim 21, wherein preventing and/or treating a disease caused by a bacterium is achieved by reversing resistance of bacteria. ### Claim 23 (depends on 21) The pharmaceutical composition according to claim 21, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier and/or excipient. ### Claim 24 A pharmaceutical kit for preventing and/or treating a disease caused by a bacterium, comprising a honeysuckle extract containing iridoid compounds and an antibiotic which are placed separately; wherein the honeysuckle extract contains secologanic acid represented by the following structural formula (1): wherein, X1 and X2 each independently represent O, and R represents H. ### Claim 25 (depends on 21) The pharmaceutical composition according to claim 21, wherein the honeysuckle extract contains 50 wt % or more of secologanic acid represented by formula (1); preferably, the honeysuckle extract contains 70 wt % or more of secologanic acid; more preferably, the honeysuckle extract contains 80 wt % or more of secologanic acid; most preferably, the honeysuckle extract contains 90 wt % or more of secologanic acid. ### Claim 26 (depends on 21) The pharmaceutical composition according to claim 21, wherein the honeysuckle extract is prepared by a method comprising the following steps: (1) pulverizing honeysuckle of plants, its original plant of lonicera japonica or other congeneric plants, and then performing extraction with water and/or C1-C6 alkyl alcohol aqueous solution containing not more than 95% alcohol by volume to obtain an extract; (2) concentrating the extract obtained in step (1) under normal or reduced pressure to obtain an extractum, or performing spray-drying on the extract obtained in step (1) to obtain power, and dissolving the extractum or power with water, then carrying out precipitation or settlement with C1-C6 alkyl alcohol aqueous solution containing not more than 95% alcohol by volume to obtain a precipitate or a dissolving liquid concentrate; (3) isolating and purifying the precipitate or dissolving liquid concentrate obtained in step (2) by chromatography, and collecting eluent containing iridoid compounds, wherein the chromatography is selected from one or more of macroporous adsorption resin column chromatography, normal phase silica gel chromatography and reversed phase silica gel chromatography; preferably, the honeysuckle extract is prepared by a method comprising the following steps: (1) pulverizing honeysuckle herbs and then performing extraction with 50% (v/v) ethanol aqueous solution to obtain an extracted liquid; (2) concentrating the extracted liquid obtained in step (1) under reduced pressure to obtain an extractum, dissolving the extractum with water, filtering, and concentrating the solution to dryness, and performing dissolution by adding 95% (v/v) ethanol aqueous solution, and adding distilled water to make the solution contain 75% (v/v) ethanol, filtering after standing, and recovering ethanol from the filtrate to obtain a fluid extractum; (3) dissolving the fluid extractum obtained in step (2) by adding water and filtering to obtain a filtrate, and making the filtrate pass through a styrene macroporous adsorption resin chromatographic column, and then eluting the column sequentially with water and 20% (v/v) ethanol aqueous solution, and recovering ethanol in the eluent of 20% (v/v) ethanol aqueous solution; more preferably, the method further comprises the step of purifying the eluent containing iridoid compounds obtained in step (3) by gel chromatography; most preferably, the method further comprises the step of purifying the eluent containing iridoid compounds obtained in step (3) by Sephadex LH-20 gel chromatographic column and collecting the eluent of water. ### Claim 27 (depends on 21) The pharmaceutical composition according to claim 21, wherein the antibiotic is selected from one or more of the group consisting of ampicillin, penam sulfone, piperacillin, tazobactam, amoxicillin, clavulanic acid, cefazolin, cefuroxime, ceftriaxone, cefuroxime sodium, sulperazon, left-handed oxygen fluorine, cefotaxime, ceftazidime, imipenem, cefepime, cefoxitin, gentamicin, amikacin, ciprofloxacin, chloramphenicol, trimethoprim-sulfamethoxazole, tetracycline, nitrofurantoin, aztreonam, ciprofloxacin, norfloxacin, ampicillin, sulbactam, ticarcillin, clavulanic acid, tobramycin, tazocin, imipenem, minocycline, meropenem, penicillin, oxacillin, erythromycin, vancomycin, rifampin and clindamycin; preferably, the antibiotic is ampicillin and/or erythromycin. ### Claim 28 (depends on 21) A use of the pharmaceutical composition according to claim 21 in the preparation of drugs for preventing and/or treating a disease caused by a bacterium. ### Claim 29 (depends on 28) The use according to claim 28, wherein the bacterium is an antibiotic-resistant bacterium, preferably multiple antibiotic-resistant bacterium. ### Claim 30 (depends on 29) The use according to claim 29, wherein the bacterium is a multiple antibiotic-resistant gram-negative bacterium; preferably, the multiple antibiotic-resistant gram-negative bacterium is selected from one or more of the group consisting of Escherichia coli, Pseudomona aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Proteus bacillus, enterobacteriaceae, Haemophilus influenzae, pneumobacillus and catarrhalis; more preferably, the multiple antibiotic-resistant gram-negative bacterium is Escherichia coli, Pseudomona aeruginosa and/or Klebsiella pneumoniae. ### Claim 31 (depends on 29) The use according to claim 29, wherein the bacterium is a multiple antibiotic-resistant gram-positive bacterium; preferably, the multiple antibiotic-resistant gram-positive bacterium is selected from one or more of the group consisting of Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Group A Streptococcus pyogenes, Streptococcus pneumoniae, Bacillus subtilis and Staphylococcus epidermidis; further preferably, the multiple antibiotic-resistant gram-positive bacterium is methicillin-resistant Staphylococcus aureus and/or Staphylococcus aureus. ### Claim 32 (depends on 28) The use according to claim 28, wherein the disease caused by a bacterium is an infectious disease caused by a bacterium, especially one or more of infectious diseases caused by antibiotic-resistant bacteria, such as digestive system infection; blood system infection; respiratory system infection; urinary tract infection; central nervous system infection; bone and joint infection; ear, mastoid and/or sinus infection; and skin and soft tissue infection; preferably, the disease caused by a bacterium is respiratory system infection caused by the antibiotic-resistant bacterium. ### Claim 33 (depends on 32) The use according to claim 32, wherein the disease caused by a bacterium is respiratory system infection caused by a multiple antibiotic-resistant gram-negative bacterium; further preferably, the disease caused by a bacterium is infectious pneumonia caused by a multiple antibiotic-resistant gram-negative bacterium; more preferably, the disease caused by a bacterium is nosocomial infectious pneumonia caused by a multiple antibiotic-resistant gram-negative bacterium; more preferably, the disease caused by a bacterium is nosocomial infectious pneumonia caused by a multiple antibiotic-resistant Klebsiella pneumoniae. ### Claim 34 (depends on 32) The use according to claim 32, wherein the disease caused by a bacterium is respiratory system infection caused by a multiple antibiotic-resistant gram-positive bacterium; preferably, the disease caused by a bacterium is pneumonia caused by a multiple antibiotic-resistant gram-positive bacteria; further preferably, the disease caused by a bacterium is pneumonia caused by methicillin-resistant Staphylococcus aureus. ### Claim 35 A use of a honeysuckle extract containing iridoid compounds in the preparation of drugs for reverting resistance of bacteria. ### Claim 36 (depends on 35) The use according to claim 35, wherein the honeysuckle extract contains secologanic acid represented by the following structural formula (1): wherein, X1 and X2 each independently represent O, and R represents H. ### Claim 37 (depends on 35) The use according to claim 35, wherein the honeysuckle extract contains 50 wt % or more of secologanic acid represented by formula (1); preferably, the honeysuckle extract contains 70 wt % or more of secologanic acid; more preferably, the honeysuckle extract contains 80 wt % or more of secologanic acid; most preferably, the honeysuckle extract contains 90 wt % or more of secologanic acid. ### Claim 38 (depends on 35) The use according to claim 35, wherein the honeysuckle extract is prepared by a method comprising the following steps: (1) pulverizing honeysuckle of plants, its original plant of lonicera japonica or other congeneric plants, and then performing extraction with water and/or C1-C6 alkyl alcohol aqueous solution containing not more than 95% alcohol by volume to obtain an extract; (2) concentrating the extract obtained in step (1) under normal or reduced pressure to obtain an extractum, or performing spray-drying on the extract obtained in step (1) to obtain power, and dissolving the extractum or power with water, then carrying out precipitation or settlement with C1-C6 alkyl alcohol aqueous solution containing not more than 95% alcohol by volume to obtain a precipitate or a dissolving liquid concentrate; (3) isolating and purifying the precipitate or dissolving liquid concentrate obtained in step (2) by chromatography, and collecting eluent containing iridoid compounds, wherein the chromatography is selected from one or more of macroporous adsorption resin column chromatography, normal phase silica gel chromatography and reversed phase silica gel chromatography; preferably, the honeysuckle extract is prepared by a method comprising the following steps: (1) pulverizing honeysuckle herbs with 50% (v/v) ethanol aqueous solution to obtain an extracted liquid; (2) concentrating the extracted liquid obtained in step (1) under reduced pressure to obtain an extractum, dissolving the extractum with water, filtering, and concentrating the solution to dryness, and performing dissolution by adding 95% (v/v) ethanol aqueous solution, and adding distilled water to make the solution contain 75% (v/v) ethanol, filtering after standing, and recovering ethanol from the filtrate to obtain a fluid extractum; (3) dissolving the fluid extractum obtained in step (2) by adding water and filtering to obtain a filtrate, and making the filtrate pass through a styrene macroporous adsorption resin chromatographic column, and then eluting the column sequentially with water and 20% (v/v) ethanol aqueous solution, and recovering ethanol in the eluent of 20% (v/v) ethanol aqueous solution; more preferably, the method further comprises the step of purifying the eluent containing iridoid compounds obtained in step (3) by gel chromatography; most preferably, the method further comprises the step of purifying the eluent containing iridoid compounds obtained in step (3) by Sephadex LH-20 gel chromatographic column and collecting the eluent of water. ### Claim 39 (depends on 35) The use according to claim 35, wherein the resistance of bacteria is resistance of bacteria to antibiotics; preferably, the resistance of bacteria is resistance of bacteria to multiple antibiotics; further preferably, the antibiotic is selected from one or more of the group consisting of ampicillin, penam sulfone, piperacillin, tazobactam, amoxicillin, clavulanic acid, cefazolin, cefuroxime, ceftriaxone, cefuroxime sodium, sulperazon, left-handed oxygen fluorine, cefotaxime, ceftazidime, imipenem, cefepime, cefoxitin, gentamicin, amikacin, ciprofloxacin, chloramphenicol, trimethoprim-sulfamethoxazole, tetracycline, nitrofurantoin, aztreonam, ciprofloxacin, norfloxacin, ampicillin, sulbactam, ticarcillin, clavulanic acid, tobramycin, tazocin, imipenem, minocycline, meropenem, penicillin, oxacillin, erythromycin, vancomycin, rifampin and clindamycin; preferably, the antibiotic is ampicillin and/or erythromycin. ### Claim 40 (depends on 35) The use according to claim 35, wherein the drug further contains an antibiotic; preferably, the drug is selected from one or more of the group consisting of ampicillin, penam sulfone, piperacillin, tazobactam, amoxicillin, clavulanic acid, cefazolin, cefuroxime, ceftriaxone, cefuroxime sodium, sulperazon, left-handed oxygen fluorine, cefotaxime, ceftazidime, imipenem, cefepime, cefoxitin, gentamicin, amikacin, ciprofloxacin, chloramphenicol, trimethoprim-sulfamethoxazole, tetracycline, nitrofurantoin, aztreonam, ciprofloxacin, norfloxacin, ampicillin, sulbactam, ticarcillin, clavulanic acid, tobramycin, tazocin, imipenem, minocycline, meropenem, penicillin, oxacillin, erythromycin, vancomycin, rifampin and clindamycin; more preferably, the antibiotic is ampicillin and/or erythromycin.