351 results about "Bactericidal effect" patented technology

The invention belongs to the technical field of antibacterial peptides, and particularly relates to an antibacterial peptide Mh-GC21 as well as a precursor and application thereof. The amino acid sequence of the antibacterial peptide Mh-GC21 provided by the invention is as shown in SEQ ID NO.1, and two cysteines are oxidized to form a pair of intermolecular disulfide bonds; the C tail end of the antibacterial peptide Mh-GC21 is subjected to amidation modification. The antibacterial peptide Mh-GC21 provided by the invention is from microhyla microcarpa, has broad-spectrum antibacterial activity, has relatively good antibacterial and bactericidal effects on standard strains of acinetobacter baumannii, escherichia coli and staphylococcus aureus and clinically sourced drug-resistant strains, and can be used for targeted destruction of cell membranes of bacteria, removal of biological membranes and inhibition of formation of the biological membranes. Moreover, the antibacterial peptide Mh-GC21 has the advantages of good stability, no hemolytic activity and cytotoxicity, and difficulty in inducing strains to generate drug resistance.

The invention belongs to the technical field of antibacterial peptides, and particularly relates to an LL-37 derived antibacterial peptide and application thereof. According to the invention, 17-29aa of the LL-37 antibacterial peptide is used as a core fragment and is connected with an amino acid sequence shown as SEQ ID NO: 1 or SEQ ID NO: 2 through an amido bond, the antibacterial activity of the obtained antibacterial peptide is obviously higher than that of the LL-37 antibacterial peptide, and the antibacterial peptide shows an obvious bactericidal effect on clinical drug-resistant bacteria such as acinetobacter baumannii, pseudomonas aeruginosa, escherichia coli, staphylococcus aureus, klebsiella pneumoniae and the like; meanwhile, the cytotoxicity and hemolytic activity are weak, drug resistance is not prone to being generated, bacteria can be rapidly killed in vivo through multiple mechanisms, no obvious cytotoxicity exists, the bacterium load in tissue is remarkably reduced, and the lifetime of a bacterium-infected mouse is prolonged.

The invention discloses an application of NSC348884 in preparation of an antibacterial drug, the bacteria of the NSC348884 are gram-negative bacteria or drug-resistant gram-negative bacteria, and the gram-negative bacteria are acinetobacter baumannii, escherichia coli, pseudomonas aeruginosa or klebsiella pneumoniae; based on an antibacterial drug high-throughput screening technology, it is found from 1280 small molecule compounds that the benzimidazole compound NSC348884 has direct bacteriostasis and sterilization effects on gram-negative bacteria and drug-resistant gram-negative bacteria, and no drug resistance is generated after the benzimidazole compound NSC348884 is continuously applied for 14 days. Further research shows that NSC348884 can interfere with lipid synthesis of gram-negative bacterium cell membranes, inhibit formation of biological membranes and induce lipid metabolism disorder, so that bacteriostatic and bactericidal effects are achieved. In addition, the NSC348884 can also enhance the sensitivity of the drug-resistant bacteria to the imipenem and the polymyxin B.

The present invention relates to the technical field of phages. Provided are a KL2-type Acinetobacter baumannii phage and a screening method therefor, a phage composition and the use, and a drug. The KL2-type Acinetobacter baumannii phage is named AB_SZL2, and is deposited in the China Center for Type Culture Collection with the deposit number CCTCC NO: M20241522; or the KL2-type Acinetobacter baumannii phage is named AB_SZL3, and is deposited in the China Center for Type Culture Collection with the deposit number CCTCC NO: M20241523. The KL2-type Acinetobacter baumannii phage can accurately target KL2-type Acinetobacter baumannii, and has an efficient bactericidal effect, thereby reducing the harm of KL2-type Acinetobacter baumannii and effectively addressing the problem of the antibiotic resistance of KL2-type Acinetobacter baumannii.

The invention provides an aeromonas hydrophila bacteriophage vBAhM7 and application thereof, and belongs to the technical field of microorganisms. According to the invention, aeromonas hydrophila is taken as host bacteria, a bacteriophage vBAhM7 is separated from sewage at a water inlet of a sewage treatment plant, and the titer can reach 109 PFU / mL; the tolerable temperature is 30-70 DEG C, and the high-temperature-resistant property is good; when the pH value is 3-12, the activity is relatively high, and the acid-base tolerance is good; the bacteriophage is not sensitive to chloroform, has no lipid coating on the shell, is stable in structure, and can resist the damage of organic solvents; the inhibition rate range on the host bacteria biofilm is 36.0%-68.6%, and good host bacteria biofilm inhibition capability is achieved; the in-vitro sterilization effect on host bacteria is good, and a relatively strong inhibition effect is achieved; the zebra fish can be protected; the antibacterial agent can be used for preventing and controlling aeromonas hydrophila in aquatic products, and the use of antibacterial agents in aquaculture is avoided or reduced.

The invention relates to the technical field of sewage treatment, in particular to a preparation method of a degradable bactericide for an oil field. According to the invention, a hydroxypropyl guanidine gum-polycaprolactone-ethylenediamine fragment copolymer is taken as a carrier, a methylisothiazolinone quaternary ammonium salt (Q-MIT) bactericide is loaded, and the degradable bactericide for the oil field is obtained by cooperating with a dodecyl ethyl sulfide (TC-SE) bactericide and combining with sodium polyaspartate. A carrier forms a hydrogen bond with a polar group on the surface of a biological membrane through a hydroxypropyl guanidine gum main chain to realize targeted anchoring, a polycaprolactone branched chain encapsulates Q-MIT through a hydrophobic effect, primary amino groups of ethylenediamine are introduced to form a pH sensitive Schiff base bond with Q-MIT, and the primary amino groups and adipic dihydrazide form a thermal response hydrazide bond to construct a dual dynamic covalent bond, so that controlled release of Q-MIT is realized, and the biomembrane is prepared. And moreover, the components of the whole system are connected through degradable chemical bonds, so that the environmental protection property and sustainability of oil field operation are guaranteed.

The invention relates to the technical field of protective films, and discloses a mobile phone protective film and a preparation method thereof. Modified graphene oxide is used as a filler, a modified waterborne polyurethane emulsion is used as a film forming substance, a flatting agent and a defoaming agent are used as auxiliary materials, a waterborne polyurethane coating is prepared, the surface of a PET base material is coated with the waterborne polyurethane coating, then drying is conducted, and the mobile phone protection film is obtained. A quaternary ammonium salt group and negative charges on a bacterial cell membrane generate electrostatic attraction, so that the original structure and function of the cell membrane are destroyed, and a bactericidal effect is achieved; silanol groups generated by hydrolysis of silane groups can react with hydroxyl groups and carboxyl groups on the surface of a PET base material, so that the interface bonding force between the coating and the base material is improved; nitrogen atoms in pyrrolidone groups form hydrogen bonds with hydroxyl groups and carboxyl groups on the surface of a base material, so that the bonding strength of the coating and the base material is further improved; the adamantyl group is grafted into the graphene oxide, so that the supporting effect of the graphene oxide on the waterborne polyurethane is enhanced, and the mechanical property of the mobile phone protective film is improved.

The invention provides a tobacco leaf nitrogen efficient sesame cake fertilizer and a preparation method thereof, and relates to the field of fertilizers. The nitrogen efficient sesame cake fertilizer for tobacco leaves comprises a solid material and water, the solid material comprises the following raw materials in percentage by mass: 60%-70% of sesame cake, 6%-8% of cottonseed cake, 12%-26% of rice husk and 8%-10% of polyaspartic acid, wherein the total mass of the raw materials is 100%. The nitrogen efficient sesame cake fertilizer for the tobacco leaves can effectively improve the quality of the tobacco leaves, improve the growth vigor of the tobacco leaves and improve the hacking degree of flue-cured tobacco leaves to a certain extent, and the cottonseed cake is added due to the fact that gossypol with a bactericidal effect is contained in the cottonseed cake, and the occurrence of soil diseases can be relieved or inhibited.

The invention discloses a copper-doped cerium oxide antifouling agent and a preparation method and application thereof.The antifouling agent takes cerium oxide as a main body material, copper is introduced for doping, Cu < 2 + > partially replaces Ce < 4 + > to enter crystal lattices, charge imbalance is caused, more oxygen vacancies are induced to be generated, meanwhile, reduction conversion from Ce < 4 + > to Ce < 3 + > is promoted, and formation of the oxygen vacancies is further stabilized. The oxygen vacancies obviously enhance the surface catalytic activity of the material, H2O2 and Br <-> in seawater can be efficiently catalyzed to generate hypobromous acid (HOBr) with a bactericidal effect, the function of natural halogenated peroxidase is simulated, and long-acting and environment-friendly biological antifouling is realized. The antifouling agent provided by the invention can be synthesized by adopting a hydrothermal method, is simple and convenient in process, is suitable for large-scale preparation, is suitable for various marine environment antifouling scenes such as hulls, marine engineering equipment and underwater sensors, and has a good application prospect.

The invention provides a compound as shown in a formula (I), a stereoisomer thereof, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a crystal form thereof, an isotope derivative thereof, a prodrug thereof and a metabolite thereof. The solvate or hydrate of the compound can be used for preparing a pharmaceutical composition for treating and / or preventing diseases related to mycobacterium tuberculosis and / or nontuberculous mycobacterium. The compound provided by the invention has an excellent bactericidal effect and strong specificity, has no cross resistance with the existing antituberculosis drugs, and provides a breakthrough direction for treatment of drug-resistant tuberculosis.

The invention discloses an antibacterial peptide PA targeting multi-drug-resistant gram-negative bacteria and application of the antibacterial peptide PA, and the amino acid sequence of the antibacterial peptide PA is shown as SEQ ID NO.1. The antibacterial peptide PA provided by the invention has a remarkable antibacterial effect of the multi-drug-resistant gram-negative bacteria, is quick in bactericidal effect, does not have hemolysis and cytotoxicity, does not cause renal toxicity after treatment, and can be used for preparing the antibacterial peptide PA for treating the multi-drug-resistant gram-negative bacteria. The biological safety is good, and the compound can be used for treating bacterial infection and can also be applied to other scenes needing sterilization or bacterial growth inhibition.

Provided are an antibacterial and deodorizing composition and a functional core prepared from the composition. The antibacterial and deodorizing composition comprises the following components in parts by mass: 10%-30% of a wormwood extract, 5%-30% of a grapefruit extract, 5%-20% of a haematococcus pluvialis extract, 5%-20% of citronellyl methylcrotonate, and the balance of a solvent. The antibacterial and deodorizing composition disclosed in the present invention not only exhibits broad-spectrum antibacterial and bactericidal effects on various microorganisms and thereby prevents symptoms such as allergy, inflammation, and erythema, but also can chelate substances such as amine, ammonia gas, and hydrogen sulfide in urine and demonstrate odor-masking effect, and thereby can effectively eliminate the odor of urine.

This invention discloses a quaternary ammonium salt / magnetic biochar composite material, its preparation method, and its application. Rice husk-based biochar is prepared using agricultural waste as raw material. Magnetic iron-based biochar is synthesized through an alkaline chemical co-precipitation method. Then, it is combined with quaternary ammonium salt compounds via ion exchange to form a quaternary ammonium salt / magnetic biochar composite material. The obtained composite material exhibits significant bactericidal effects and superior slow-release quaternary ammonium salt performance. Furthermore, the used quaternary ammonium salt / magnetic biochar composite material can be used to prepare a regenerated quaternary ammonium salt / magnetic biochar composite material, with better bactericidal effects than the initial use, achieving the recycling and reuse of the composite material. The preparation method of this invention uses widely available and inexpensive raw materials. The obtained composite material adsorbs free bacteria through high-density charge adsorption, avoiding the development of drug resistance and secondary environmental pollution. It can be applied to wastewater treatment, providing a new material and method for solving the problem of pathogenic bacteria pollution in water bodies.

The present application relates to the field of biotechnology, in particular to a carbapenem-resistant escherichia coli phage and application thereof.A new escherichia coli phage vB_EOP_Se009 is isolated and purified, and the phage has good sterilization effect on carbapenem-resistant escherichia coli.The phage has strong tolerance to temperature and pH, is high in specificity and stability, can effectively solve the problem that carbapenem-resistant escherichia coli is resistant to multiple antibiotics, and provides an experimental basis for developing a preparation for preventing or treating carbapenem-resistant escherichia coli infection in clinic, and has great clinical application potential.

The application discloses an antibacterial peptide RV15 and application thereof, and belongs to the technical field of biology. The amino acid sequence of the antibacterial peptide RV15 is shown as SEQ ID NO. 1. The antibacterial peptide RV15 provided by the application has broad-spectrum antibacterial activity, has a significant bacteriostatic effect on gram-positive bacteria and gram-negative bacteria, and has a long bactericidal duration. The hemolytic activity is very low, and the biological safety is good. The antibacterial peptide RV15 can be used for treating bacterial infection, and can also be applied to other scenes requiring bactericidal action or bacterial growth inhibition. The antibacterial peptide RV15 provided by the application has a short sequence, a small molecular weight and low chemical synthesis difficulty, and can save the production cost on a large scale.

The application belongs to the technical field of antibacterial peptides, and particularly relates to an antibacterial peptide Mp-GC21, a precursor thereof and application. The amino acid sequence of the antibacterial peptide Mp-GC21 is shown as SEQ ID NO:1, wherein the C terminal is subjected to amidation modification, and two cysteines are connected through a disulfide bond; and the amino acid sequence of the precursor is shown as SEQ ID NO:3. The antibacterial peptide Mp-GC21 is separated from the flower frog, has broad-spectrum antibacterial activity, and has good bacteriostatic and bactericidal effects on standard strains and clinically derived drug-resistant strains of Acinetobacter baumannii, Escherichia coli and Staphylococcus aureus, and can target to destroy the cell membrane of bacteria, remove the biofilm and inhibit the formation of the biofilm. Moreover, the antibacterial peptide Mp-GC21 has good stability, does not have hemolytic activity, cytotoxicity and in-vivo toxicity, and is not easy to induce drug resistance of strains.

The application relates to the fields of biological medicine and aquaculture, and discloses a zebrafish IFNf interferon truncated protein and application thereof in antibiosis. The zebrafish interferon derivative peptide AMP-Z2 can specifically inhibit fungi. The interferon derivative peptide provided by the application is a host natural peptide, has small molecular weight, is simple to synthesize, has significant bactericidal effects on various bacteria and fungi, and can be used for preparing broad-spectrum antibacterial agents or antibacterial drugs.

The utility model discloses an ozone on-line mixed disinfection system, which belongs to the technical field of disinfection systems, aims to solve the problems that the concentration of ozone in an ozone tank is inconvenient to control, the ozone is easy to waste when the concentration is too high, and the sterilization effect on water cannot be ensured when the concentration is too low, and comprises a mounting tank, an ozone bin, a multi-stage disinfection bin and a liquid and gas discharging bin are sequentially arranged in the mounting tank from top to bottom, a liquid inlet pipe is mounted on the side face of the mounting tank, water needing to be disinfected is added into the multi-stage disinfection bin, and the ozone bin can introduce ozone into all bins in the multi-stage disinfection bin. Therefore, the pressure in the ozone bin can be controlled, so that a corresponding amount of ozone is introduced into each bin in the multi-stage disinfection bin, and the disinfection operation is carried out, so that the disinfection effect is ensured, and meanwhile, the situation of ozone waste is avoided.

The invention belongs to the technical field of traditional Chinese medicines, and relates to a method for improving the sensitivity of streptococcus mutans to a glycyrrhiza uralensis extract. According to the method, the glycyrrhiza uralensis extract and hydrogen ions jointly act on streptococcus mutans in an acid environment. Research finds that the inhibitory activity of part of the effective components of the glycyrrhiza uralensis extract on streptococcus mutans in an acid environment is remarkably enhanced. The glycyrrhiza uralensis extract and hydrogen ions have a synergistic effect, and the acidic environment can improve the sensitivity of the isostreptococcus to the glycyrrhiza uralensis extract and enhance the bactericidal effect.

Provided is a novel compound having an excellent antibacterial or bactericidal effect.　This copolymer includes a structural unit represented by formula (1) and a structural unit represented by formula (2). [In formula (1), R1 represents an (un)substituted C1-C20 alkanediyl group and R2 represents -N+R3R4R5Y- or -NR6R7 (wherein R3, R4, R5, R6, and R7 each independently represent a hydrogen atom or an (un)substituted C1-C20 hydrocarbon group and Y- represents a counter anion).] [In formula (2), R8 represents a hydrogen atom or an (un)substituted C1-C20 hydrocarbon group.]

This invention discloses the application of ferrous ions in the preparation of products for treating bacterial infections, belonging to the field of pharmaceutical technology. Antibacterial activity tests of ferrous ions against Staphylococcus aureus showed strong bactericidal effects, with a survival rate of less than 0.001% against Staphylococcus aureus and less than 0.01% against methicillin-resistant Staphylococcus aureus (MRSA). The use of ferrous ion-containing hydrogels in the treatment of keratitis and skin wound infections significantly reduced the risk of MRSA infection in the lungs and effectively prevented the proliferation and spread of microorganisms in the body, revealing that drugs containing ferrous compounds can be used to treat Staphylococcus aureus infections, including MRSA.

The invention relates to a veterinary hoof disease prevention and treatment composition as well as a preparation method and application thereof, and aims to solve the technical problems that existing commercial hoof bath lotion is limited in sterilization effect and relatively strong in local irritation, and a safe and efficient treatment medicament for treating cow hoof warts is lacked and the like. The invention provides a veterinary composition which comprises the following active ingredients: a glycyrrhizic acid compound, didecyl methyl ammonium bromide and polyhexamethylene guanidine salt, and the three components are combined, so that the composition has an antibacterial effect and an effect of promoting skin tissue repair at the same time. A series of tests prove that the traditional Chinese medicine composition can effectively inhibit animal pathogenic bacteria, prevent and / or treat animal limb and foot diseases and promote healing and repairing of ulcer injury. The medicament disclosed by the invention is suitable for preventing and treating limb and hoof diseases in a large-scale pasture, has the characteristics of high sterilization efficiency, good safety and effective treatment, and can improve the animal hoof health management level.

This invention relates to the field of oral care products technology, specifically to an artificial enzyme with antibacterial properties, its preparation method, and its application. This technical solution employs a chemical reduction method, where a palladium source reacts in an environment containing surfactants and reducing agents to obtain palladium nanozymes. The obtained palladium nanozymes exhibit uniform morphology, controllable particle size, good dispersibility in water, and good biocompatibility; they have no significant toxic side effects on human gingival fibroblasts, possess highly efficient catalase activity, and demonstrate strong antibacterial and bactericidal effects against oral pathogens, significantly reducing bacterial drug resistance; they can inhibit acid production by oral bacteria, preventing tooth decay; and they retain their original catalytic activity even after multiple cycles of use. Applying the palladium nanozymes of this solution to the manufacture of oral care products can solve the technical problems of unsatisfactory safety and easy development of drug resistance in existing oral care products using antibacterial and anti-caries methods, showing promising application prospects.

The invention relates to a bimetallic alloy nano-enzyme for treating multi-drug-resistant bacterial infection as well as a preparation method and application thereof, and belongs to the field of biomedical nano-materials. The problems that in the prior art, the catalytic activity of metal and metal-based nano enzyme is limited, the bactericidal effect is poor due to poor targeting performance, the bactericidal effect in vivo (especially deep drug-resistant bacteria) is poor, and biocompatibility is poor are solved. The invention relates to a bimetallic alloy nano-enzyme for treating multidrug-resistant bacterial infection, which is mainly composed of two metal elements of Pt and Ru, and the atomic ratio of Pt / Ru is 90 / 10-70 / 30. The bimetallic alloy nano-enzyme disclosed by the invention has efficient biological catalytic activity, has a very good treatment effect on deep drug-resistant bacterial infection under ultrasonic activation, shows remarkable antibacterial, anti-biofilm and anti-inflammatory multiple effects, and is good in biocompatibility.

The invention relates to the technical field of bactericides for crops, in particular to a bacillus cereus-containing bactericidal composition and application thereof in prevention and control of camellia oleifera anthracnose. The active ingredients of the bactericidal composition comprise bacillus cereus WR-12 and diflumetofen sulfanilamide. According to the bactericidal composition, the synergistic bactericidal effect is enhanced by compounding a biological fungicide and a chemical fungicide, the development of drug resistance of pathogenic bacteria is delayed, the negative influence of chemical pesticides on the environment is reduced, green and efficient prevention and control of camellia oleifera anthracnose are achieved, and sustainable development of the camellia oleifera industry is promoted.

This invention discloses a method for preparing and applying a photothermal nanoreagent targeting bacteria. This invention utilizes Ti3C2T... x Using MXene as a matrix, a photothermal nanoreagent MXene@PDA@Peptide (MPP) was constructed by sequentially modifying the surface of Ti3C2Tx MXene with polydopamine and grafting it with the peptide CAEKA, which has the function of recognizing bacteria. Under the recognition of the peptide CAEKA, the photothermal Ti3C2Tx MXene was targeted. x MXene nanosheets are guided to the surface of bacterial cells, achieving effective sterilization at a relatively low overall temperature of around 50°C (or achieving more efficient sterilization at the same overall temperature level, exhibiting superior sterilization performance compared to pure Ti3C2Tx MXene). This makes them particularly suitable for the preparation of therapeutic drugs for subcutaneous abscesses caused by methicillin-resistant Staphylococcus aureus (MRSA) infection.

The present application relates to the technical field of deodorant, and disclose a kind of biological deodorant for pasture and preparation method thereof, the present application is by adding cortex moutan extract, alkyl dimethyl benzyl ammonium chloride, modified chitosan, imidazole modified triazine base compound, lemon essential oil into stirrer, stir, after obtaining biological deodorant for pasture.The imidazole group, quaternary ammonium salt group, sulfonate sodium group triazine group in imidazole modified triazine base compound and modified chitosan all have good bactericidal effect.The triazine group in it can effectively kill bacteria, fungi and other microorganisms in animal manure, feed residue and other organic matters, thereby preventing the spread of odor;The imidazole group in it can inhibit the growth and reproduction of pathogenic bacteria, reduce the occurrence and spread of disease, and play a role in killing bacteria;The quaternary ammonium salt can effectively inhibit the growth and reproduction of microorganisms, can reduce the foul-smelling gas generated by the decomposition of organic matter by microorganism, thereby achieving the effect of deodorization.

The present invention belongs to the technical field of pesticides, and specifically relates to a pyridine amide compound and the use thereof. The compound is as represented by formula I, wherein W1 is O or S; R1 is hydrogen, alkyl, alkenyl, alkynyl, etc.; R3, R4 and R5 are each independently hydrogen, halogen, alkyl, etc.; and X1, X2, X3, X 4, X5, Y1, Y2, X3 and Y4 are each independently hydrogen, halogen, alkyl, etc. The compound has a good bactericidal effect.

The invention discloses a chemotactic response type self-assembly antibacterial peptide and a preparation method and application thereof, the antibacterial peptide comprises: (a) a targeting module, the amino acid sequence of which is selected from KPRSVS or a variant thereof, GPLVPRG or a variant thereof, and GPLGVRG or a variant thereof; (b) a self-assembly module which is composed of hydrophobic residues and hydrophilic residues which are alternately arranged and forms beta-folding driving nanofibers; (c) an inflammation response module which is selected from a histidine enrichment region, an ROS sensitive group or an MMP protease cleavage site and is used for responding to an inflammation microenvironment and enhancing target site enrichment; (d) a stability enhancing module comprising at least one of D-type amino acid modification, N-terminal PEG4 connection or cyclization structures. The antibacterial peptide disclosed by the invention has chemotactic effect on an inflammatory microenvironment, can accurately identify gram-negative bacteria, is triggered in the inflammatory environment, and plays an accurate bactericidal effect on various pathogenic bacteria.

The invention relates to the technical field of biological medicine, in particular to a composition for blocking formation of phage treatment tolerance and application of the composition. The composition comprises a folium ilicis purpurea ethyl acetate extraction active component and a clostridium perfringens specific bacteriophage, the folium ilicis purpurea ethyl acetate extraction active component is prepared from the following components in percentage by mass: 8 to 15 percent of protocatechuic acid and 5 to 10 percent of ethyl gallate, and the mass ratio of the protocatechuic acid to the ethyl gallate is (1.5 to 1) to (2.5 to 1); the clostridium perfringens specific bacteriophage is a virulent bacteriophage capable of specifically cracking a clostridium perfringens NetB toxin positive strain. According to the invention, the shallow thought that the existing compounding technology only pursues synergistic sterilization is subverted, and a deep synergistic mode of bacteriophage splitting attack and folium ilicis purpurea component disintegration bacterial defense program is proposed and verified for the first time. And the formation of tolerance is fundamentally blocked, so that a more thorough and more lasting treatment effect is realized, and the comprehensive production performance of animals is accidentally and greatly improved on the basis of the treatment effect.