CN105582529A - Pharmaceutical composition for treating beriberi - Google Patents
Pharmaceutical composition for treating beriberi Download PDFInfo
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Abstract
The invention relates to a pharmaceutical composition for treating beriberi. The weight ratio of the active ingredient lysozyme to the active ingredient osthole is (1:10)-(10:1). Compared with ordinary western medicine preparations, the lysozyme preparation has the advantages that the preparing method is simple, compatibility of medicines is high, and the two active ingredients have their own functions and can also generate synergistic interaction so as to treat beriberi remarkably. Lysozyme and osthole both have natural sources and are safe, free of toxin and free of side effect. Due to the fact that no western medicine antibacterial agent is contained in the pharmaceutical composition, the pharmaceutical composition has no drug resistance.
Description
Technical field
The present invention relates to pharmaceutical field, be specifically related to a kind of medicine for the treatment of beriberi.
Background technology
Beriberi, medically claiming again " tinea pedis " to be commonly called as " athlete's foot ", is foot fungus infection. Show as between toe or volaPruitus, erythema, papule, decortication, or have bubble, seriously can be rotten to the corn, ooze out. As control not in time can involve itHis position, causes ringworm of the body, jock itch or " onychomycosis ". Medically conventionally beriberi is divided to three types: erosive type, vesicle,Keratinization type beriberi. Erosive type is apt to occur between the 3rd and the four, four and the 5th toe. From the beginning of moist between toe, dipping turn white orPlay phlysis, after dry furfur, peelling off scurf is rotten to the corn face moistening, flush, odd itching, easily scabies secondary infection. BlisterType is apt to occur in sufficient edge. From the beginning of being the full phlysis of wall thickness, the be fused into bleb having, blister liquid is transparent, around without redDizzy. Consciously very itch, after scratching often because scabies secondary infection causes erysipelas, angioleucitis etc. Keratinization type is apt to occur in heel. MainShow as skin thick thick and dry, angling furfur, scratch where it itches, easily chap. This type is without blister and suppuration, and the course of disease is slowSlowly do not heal for many years.
Can be divided into three types according to beriberi, methods for the treatment of is also because type is different. Angling drying type patient, medication should be with creme, pasteBe main; If bubble wastes the patient of rotten type, i.e. affected part infiltration, should first process more dryly by affected part, and then use powderAgent medicine is treated; Also have a class patient to belong to mixed type, the position having is dried, decortication, and rotten stream is wasted at some positionsWater, now just medication as the case may be. Except distinguishing type medication, patient also should pedicure journey medication under doctor's guidance.Often treat with antifungal drug, conventional product has Da Kening, Lan Meishu, Pevisone, PIKANGWANG and ZUGUANG SAN etc.
Clinical pharmacology research shows, medication nitrofurazone 0.5g, and boric acid 5g, benzoic acid 5g, salicylic acid 5g, tannic acid 5g, grindsLast treatment beriberi is 99.48% to the cure rate of 191 routine patient treatments. Use atropine 1.2g, nystatin 5*106U，Aspirin 1.5g, kuh-seng 5g, climbing groundsel 5g, talcum powder 5g. Each medicine is ground into powder above, mix, every day in noon,After foot bath in night is dried, get appropriate medicinal powder and be spread on affected part, treatment patient 154 examples, recovery from illness 98 examples, effective 42 examples, effective 14Example. 31 examples are cured 3 months state of an illness and are again recurred, through again treating recovery from illness, total effective rate 100% with medicine-feeding. Get benzoic acid,Salicylic acid, realgar mix, and cross 60 mesh sieves, and 750g vinegar put into by medicine one bag by every bag 30g, stirs evenly and treat that large portion is moltenSeparate. Affected part is saturating with Warm Wash, removes Lao Pi, dries, and more than immersing the interior 1h of above-mentioned liquid, dries. Through clinicalObserve checking permeability strong, effect is lasting, easy to use, evident in efficacy. With warm water foam washing biped, after drying, get 75%Cotton ball soaked in alcohol is embrocated affected part repeatedly, and 1 time every night, footwear are cleaned up simultaneously, after drying, get 75% cotton ball soaked in alcohol wiping footwearIn. This group all obtains effect through treating, and itch and fash disappear. Wherein 1 person's of being cured 22 example, 2 person's of being cured 9 examples. Follow up a case by regular visits toRecurrence in the shortest 3 months, recurrent cases continues and still can cure by this law.
In recent years, there are some researches show that acupuncture and laser therapy can treat beriberi equally. Get Ipsilateral Zusanli, SANYINJIAO acupoint,Routine disinfection. Patient's dorsal position, with No. 28 2 cun of acupuncture needles, first acupuncture Sanyinjiao, pin sense is conducted downwards, and shank is upwards twitched2 times, and then acupuncture at Zusanli, pin sense for good, is thrusted straightly 1 cun-15 cun to foot conduction, let the acupuncture needle remain at a certain point 30min, interval 10minHandle the needle 1 time, every day 1 time, 5 statistics curative effects. Treat in 48 examples, recovery from illness 43 examples, account for 89.58%; Effective 5 examples, account for 10.42%,Total effective rate 100%. Adopt the multi-functional CO of DJZ-B type2Laser cure apparatus, power 30W-50W, adjustable continuously, suffer from footAfter disinfecting, use CO2Laser physical therapy camera lens is apart from surface of a wound 3cm-5cm, rotary irradiation, and the time is 15min-20min,Once a day, dry incrustation after 3d-5d, various transference cures and fully recovering.
At present, the medicine that is used for the treatment of on the market beriberi is mainly Western medicine antiseptic, and long-term use easily produces drug resistance. CauseThis, be necessary to research and develop a kind of medicine natural, that have no side effect, have no drug resistance of originating and replace antiseptic to use.
Lysozyme (lysozyme) claims again muramidase (muramidase) or N-acetylmuramide lycanohydrlase(N-acetylmuramideglycanohydrlase), be a kind of alkaline enzyme that can be hydrolyzed glutinous polysaccharide in pathogenic bacteria. Main logicalCross the β-Isosorbide-5-Nitrae glycosidic bond between-acetylmuramic acid and the NAG destroying in cell membrane, make cell membrane insolubleProperty glutinous polysaccharide resolve into solubility glycopeptide, cause cell wall rupture content to be overflowed and make bacterolysis. Lysozyme also can be withThe direct combination of electronegative virus protein, forms double salt with DNA, RNA, apoprotein, makes virally inactivated. CauseThis, that this enzyme has is antibacterial, anti-inflammatory, the effect such as antiviral. Lysozyme (also claiming lyase) is that a molecular weight is 14.4kDaEnzyme, it can by between-acetylmuramic acid in catalysis peptide glycan and 2-Acetamido-2-deoxy-D-glucose residue and chitodextrin inThe hydrolysis of the Isosorbide-5-Nitrae-β chain between N-acetyl-glucosamine residue, and destroy the cell membrane of bacterium. In human body, lysozyme is at cellJuice, as extensively existed in saliva, tears and some other body fluid; Also be present in the cytoplasmic granule in mitochondriaIn body. In addition, in egg white, also there is a large amount of lysozymes. Lysozyme is because of the cell that acts on object microorganism that can be single-mindedThe alkali hydrolysising protease of wall, is applied to the industries such as food, feed, medicine widely.
Lysozyme (lysozyme) is by the simple alkaline globulin of 18 kinds of 129 Amino acid profiles, and molecular weight is 14.4KDa.Chemical property is highly stable. In pH value is 1.2～11.3 scopes, when acute variation, its structure is almost constant. At acyclic acidicIn border, lysozyme is very strong to hot stability; In the time that pH value is 4～7,100 DEG C of processing 1min still can keep original enzyme activity;100 DEG C of heat treated 45min of ability in the time that pH value is 3; Under drying condition, lysozyme can be deposited in room temperature for a long time,Its sterling is white or micro-yellow. Yellow crystalline solid or amorphous powder, odorless, taste is sweet. Soluble in water, suffer alkali easyDestroy, be insoluble to acetone and ether. As medical supplies, lysozyme have good biocompatibility, non-stimulated to organizing,The advantages such as nontoxicity.
Lysozyme is extensively present in the egg white of poultry, birds and mammiferous tear, saliva, blood plasma, urine, milk, whiteIn cell and other body fluid and tissue (as liver, kidney) cell; From barley, fig, pawpaw and cabbage, radish etc.In plant, also can isolate lysozyme, wherein with content in egg white for the highest (approximately containing 0.3%). And human milk, tears, salivaLysozyme activity in liquid is far above (being about 3 times) in egg white or the activity of the lysozyme in other sources. In eggLysozyme is the Typical Representative of animal lysozyme, is research object important in lysozyme group, is also that understanding is the clearest at presentOne of lysozyme. In mammiferous milk, the lysozyme content in human milk is 3000 times of cow's milk. By sourcesDifference, lysozyme can be divided into egg white lysozyme, animal lysozyme, plant lysozyme, microorganisms lysozyme andThe lysozyme that bacteriophage produces; By function cells wall difference, lysozyme can be divided into bacteria cell wall lysozyme and trueBacterial cell wall lysozyme.
Lysozyme can single-minded cracking object bacterium cell membrane. Its main attack peptide glycan, hydrolysis connects N-acetyl cell wallβ-Isosorbide-5-Nitrae glycosidic bond of acid and the 4th carbon atom of N-acetyl-glucosamine. Whole process is that first lysozyme is by two" ditch " between domain is attached on peptide glycan molecule; Its substrate forms the conformation of transition state in enzyme subsequently. According toPhillips mechanism, lysozyme is combined with glucohexaose. Then lysozyme is half chair by the 4th sugared distortion on glucohexaoseShape conformation. In this twisted state (energy is higher), glycosidic bond is easy to just rupture. Be positioned at antalzyme proteinThe side chain of the glutamic acid (Glu35) that sequence is 35 and the aspartic acid (Asp52) of 52 to the activity of lysozyme veryCrucial. Glu35, as the proton donor of glycosidic bond, shears the C-O key of substrate; And Asp52 participates in as nucleopilic reagentGenerate glycosyl enzyme intermediate. Subsequently, glycosyl enzyme intermediate and hydrone react, and hydrolysis generates product, and enzyme keepsConstant.
The extracting method of lysozyme comprises following several: 1, direct crystallization method: this method is simple to operate, and cost is low, but can notIn order to separate micro-lysozyme. 2, ion exchange chromatography: this method have easy, efficient, cost is low, and can be automaticChange the advantage circle of continued operation. 3, affinity chromatography: the multiple of affinity chromatography separation and purification is higher, quality is better, and canBe widely used in the lysozyme in various sources, for concentrated and refining micro-lysozyme. But due to affinity adsorbentMake more complicatedly, limited it in industrial extensive utilization. 4, ultrafiltration is combined with affinity chromatography: ultrafiltration and affine layerAnalysing in conjunction with extracting lysozyme, is the new method of developing in recent years. First remove most of foreign protein with ultrafiltration, retain bacteriolyzeEnzyme, now lysozyme is also thicker, then obtains purified product with affinity chromatography. 5, membrane chromatography technology: 80 years 20th century, there is affinity film chromatography technology in Dai Mo. This technology has film concurrently and separates and the affine feature separating. Separate with traditional film,Affinity chromatography is compared, and membrane chromatography technology not only has that purification is high, pressure drop is little, disengaging time is short, large biological molecule existsIn separation process, sex change probability is little, and allows the feature such as charging rate faster, and more easily realizes than post affinity chromatographyLarge-scale production. 6, ultrafiltration: compared with traditional biochemical isolation technics, the main advantage of hyperfiltration technique is the high yield of productOutput. Although but hyperfiltration technique is widely used in reverse osmosis and the process such as concentrated, conduct is in biological workThe very large a kind of protein stripping technique of potential in industry field, ultrafiltration is fully utilized not yet. 7, reverse micelle extracts: anti-glueGroup extraction is a kind of new extracting process that developed recently gets up, and it is to utilize in organic solvent, to add a small amount of surfactantThe method that the reverse micelle forming extracts, lives for some enzyme and reactive proteins etc. that can not with an organic solvent extract are biologicalProperty material has been opened up a kind of new isolation technics, has expanded the scope of application of organic solvent extraction. 8, bioseparation technology:Taking affinity as basic bioseparation technology (immobilized metal affinity chromatography, affinity precipitation, affinity filtration method), be alsoOne of lysozyme extracting method.
Lysozyme has multiple uniqueness and important pharmacological action.
The first, anti-inflammation. The cell membrane of bacterium is made up of murein, and murein is by 2-Acetamido-2-deoxy-D-glucose and N-Acetylmuramic acid is the polymer of composition alternately, on cell wall residue, can connect polypeptide, is called peptide glycan. Polysaccharide is with straight chain shapeFormula exists, and can interconnect by peptide chain part, thereby form three-dimensional structure between polysaccharide chain located adjacent one another. BacteriolyzeAct on the glycosidic bond between-acetylmuramic acid and the N-acetyl glucosamine ammonia of peptide glycan molecule, result makes enzyme specificityIt is loose that bacteria cell wall becomes, and loses the protective effect to cell, last cytolysis death; Lysozyme can directly be killedGram positive bacteria, in the presence of S-IgA complement, can also kill gram-negative bacteria: as large intestine dust Xi ShiBacterium. Lysozyme also can be combined with the various acidic materials that bring out inflammation, reduces bacterial endotoxin and discharges, thereby alleviate endogenous toxic materialElement mass formed by blood stasis occurs, and slows down inflammation generating process, and antibiosis is have to certain synergistic effect, improves the glutinous polysaccharide of periplastMetabolism, plays the effect of anti-inflammation, repair tissue. Through evidence, with a kind of cellulose copolymer by human lysozymeWith proteolytic enzyme coupling, can significantly improve lysozyme antibiotic ability, accelerating wound healing.
The second, antiviral. Lysozyme under neutral body pendular ring border with a large amount of positive charges, can with the viral egg with negative electrical chargeWhite direct effect, the formation double salt that combines with DNA, RNA, desorption base albumen, makes virally inactivated. By herpesviral senseAfter adding lysozyme in the Hela cell culture fluid dying, there is the effect of the cell degeneration of inhibition. Lysozyme also can suppress adenovirus growth,Can be used for the viral illness treatment such as herpes zoster, mumps, chicken varicella, hepatitis and influenza.
The 3rd, strengthen immunity. Lysozyme participates in panimmunity reaction in body, the normal defence of body and non-specific exempting fromIn epidemic disease, there is important function. It can improve and strengthen macrophage phagocytic digestive function, reduces white that cytostatics causesLeukopenia, in conjunction with bacteria lipopolysaccharide, alleviates endotoxin effect, to reach the object that strengthens Abwehrkraft des Koepers. LysozymeItself has t cell epitope, can induce the reaction of 2 types (Th2) t helper cell. Oral lysozyme energy inducing mouse producesGeneral Th1 and Th2 immune response, strengthen immunologic function, and therefore, oral lysozyme has the control infection of the upper respiratory tractFunction with treatment dysentery. In addition, lysozyme also has the hematoblastic function of activation, can improve tissue local blood circulationObstacle, decomposes fester, strengthens local defense function, thereby embodies its hemostasis, detumescence and accelerate repairing of body injury tissueMultiple effect. It also can be used as a kind of host's resistance factor, and tissue local is shielded.
Scientific research personnel has accumulated a large amount of experiences of lysozyme application aspect clinical testing. For example, drug sensitive test is with compoundLysozyme, Fluconazole and 3 kinds of medicines of nystatin are trial drug, study their antibacterial to separated Candida albicansEffect, adopts NCCLSM27-A micro-dilution method to measure the MIC value of medicine. The antimycotic susceptibility test card of three kinds of medicinesBright: composite lysozyme, Fluconazole and nystatin are respectively for the minimal inhibitory concentration of separated Candida albicans2.03 μ g/ml, 3.19 μ g/ml and 6.03 μ g/ml; The sensitiveness of composite lysozyme is greater than to Fluconazole to Candida albicans and system is mouldRhzomorph; Clinical observation on the therapeutic effect research shows: the efficient of composite lysozyme treatment children's thrush is 97.5%, brightAobvious higher than contrast nystatin group; The treatment time average out to 6.46d of composite lysozyme group, is starkly lower than contrast nystatinThe 13.0d of group; Its result of study shows: Candida albicans is the highest to the sensitiveness of composite lysozyme, is greater than Fluconazole and systemMoldin. Composite lysozyme is used for the treatment of children's's thrush, short treating period, and cure rate is high. Composite lysozymeAntimycotic external drug sensitivity tests consistent with clinical efficacy, show that drug susceptibility and clinical efficacy exist certain correlation.Separately there are some researches show, children's acute nasosinusitis is under lysozyme auxiliary, and symptom rapidly disappears in 14d left and right, and schneiderian membrance is extensiveMultiple normal, and the children's acute nasosinusitis healing time of control group is obviously longer than seminar, shows that lysozyme has auxiliary efficientlyHelp antibacterial functions; Seminar and control group, all having significant difference aspect cure rate and obvious effective rate, prove lysozyme toolThere is remarkable quickening children's acute nasosinusitis recovery from illness speed, and not yet find bad reaction, have certain clinical application valencyValue. Because prevention and the treatment of lysozyme to diseases of the five sense organs has good curative effect, at present domestic have lysozyme lozenge to go on the market,Lysozyme has broad application prospects at treatment diseases of the five sense organs.
Osthole has another name called osthole (osthole), and its chemical name is osthole.Osthole is a kind of coumarin kind compound extracting from the fruit of Umbelliferae frutus cnidii platymiscium cnidium monnieri, is frutus cnidiiA kind of alkyl Coumarins active chemical of middle content the highest (approximately 1%), is colourless column crystallization, and molecular weight is244.29,82 DEG C-84 DEG C of fusing points. Osthole is mainly present in 14 platymisciums of Umbelliferae and 17 genus of RutaceaeIn plant, in composite family and pulse family minority plant, also there is distribution. Modern pharmacology experimental study shows, Osthole has anti-high bloodPressure, anti-arrhythmia, anti-ageing, antitumor, anti-osteoporosis disease, the effects such as anti-inflammatory and antiallergic action.
Osthole significantly strengthens the syngignoscism of subthreshold hypnotic dosage yellow Jackets to mouse, and this effect and dosage phaseClose. The medicine that reduces yellow Jackets metabolism in view of only affecting liver drug enzyme is invalid to this model, and this points out frutus cnidiiElement can play a role by suppressing central nervous system. The mouse writhing reaction that Osthole Dichlorodiphenyl Acetate causes is dosage phaseThe obvious inhibitory action of closing property, but the hot plate method induced pain mouse threshold of pain is affected without obvious, this may be OstholeCalmness but not due to analgesic activity. Although Osthole does not affect the autonomic activities of normal mouse, be dosage correlation groundResist the increase of low dose of caffeine sodium benzoate induced mice autonomic activities number of times, this prompting Osthole may be by suppressing brain skinLayer and performance sedation.
Frutus cnidii have the effect that promotes learning and memory of little mouse, can significantly improve mouse memory acquisition, consolidation and direction identification barrierHinder, but memory represents obstacle is not improved. Osthole can also significant prolongation mouse hypoxia endurance time, suppresses ratThe generation of MDA in liver, brain, the activity of reduction mouse whole blood, Cerebral cholinesterase, by dividing its mechanismAnalyse, think may with affect brain in cholinesterase activity and to delay the factors such as cell senescence relevant. Osthole AlCl3Cause urgencyProperty aging model memory deficits in mice have protective effect, its mechanism of action may be by strengthening glutathione peroxidase(GSH-PX) and erythrocuprein (SOD) activity remove the damage of oxygen radical to central nervous system nerve cellWound. In addition, Osthole can also promote the learning and memory function of experimental rats with deficiency of kidney-Yang, corrects smart ammonia element simultaneously and boostsThe metabolic disorder of element and growth hormone release inhibiting hormone.
Osthole can significantly improve rats with deficiency of kidney-Yang serum thyroid stimulating hormone and 3 kinds of thyroid hormone (T3, anti-T3And T4)Concentration, show that it can improve rats with deficiency of kidney-Yang adenohypophysis-thyroid axis function. Osthole can the hydrogenation of antagonism acetic acid canThe feedback inhibition of pine to adrenal cortex function, the concentration of raising plasma corticosterone, corticotropin, toolThere is the effect of protection and enhancing adenohypophysis-adrenal cortex s function. In addition, Osthole can antagonism propylthiouracil(PTU) suppressed thyroid tissue effect, stops T effectively3，rT3And T4Concentration declines, and obviously reduces mouse death rate,Promote body weight to increase, the appearance of prevention " kidney-yang deficiency " disease, can promote again due to PTU that first subtracts in " kidney-yang deficiency " Mice BodyThe raising of thyroid hormones level, has tonifying kidney and strengthening yang effect.
The Annexation that Osthole can strengthen mouse reticuloendothelial cell bites function, and significantly increase carbon particle clearance index and Annexation and bite index,Significantly increase spleen index, show that Osthole can strengthen nonspecific immunity of mice. Adopt hydrocortisone to cause littleMouse kidney-yang deficiency model, finds that Osthole can significantly improve peritoneal macrophage phagocytic percentage and Annexation bites index, serum is moltenSanguinin 50% haemolysis value, SPL3H-TdR mixes number, shows that Osthole can strengthen the immune merit of mice with kidney-yang deficiencyEnergy.
Osthole can suppress mouse passive cutaneous anaphylaxis strongly, and overall guinea pig tissues amine is panted and had protection to doWith, the isolated guinea pig ileum that slow reacting substance is caused shrinks and Schultz-Dzlc reaction is obvious antagonism and blocking-up is doneWith, and can suppress the de-particle of rat peritoneal mast cells, can also obviously suppress mouse delayed type hypersensitivity, DTH. These researchsResult shows, Osthole has anti-allergy action.
Osthole can obviously suppress acute and chronic inflammation, can alleviate little that auricular concha swelling that dimethylbenzene causes and acetic acid causeMouse abdominal cavity capillary permeability increases, and obviously suppresses the mouse granuloma that agar causes, on Carrageenan and excision bilateralThe rat paw edema that adrenal gland brings out all has obvious inhibitory action, but does not affect prostate in rat foot claw inflammation tissueElement (PEG) content, shows that its anti-inflammatory mechanisms is not by Pituitary Adrenal cortex system, also has nothing to do with the synthetic of PEG,May be to bring into play antiinflammatory action by strengthening non-specific immune function and/or antiallergic action.
Osthole forms and bone absorption by reducing the bone of ovariectomized female rats, and is absorbed as master to suppress bone, increases bone amount,Can effectively prevent and treat the high conversion hysteria osteoporosis of ovariectomized in rats, prevent bone loss, maintain the balance of bone metabolism, butIts effect is lower than Nilestriol. Isolated experiment shows, Osthole energy stimulating osteoblast 3H-thymidine and 3H-dried meat ammoniaAcid incorporation, points out it to have the osteoblastic propagation of stimulation in rats and gelatine synthesis; At Gegenbaur's cell alkaline phosphataseWhen enzymatic activity is the highest, Osthole significantly increases the activity of Gegenbaur's cell alkaline phosphatase; Show that Osthole increases bone amountBasis be promote osteoblastic osteogenic action. In addition Osthole can be suppressed to osteocyte spontaneously or at inflammatory cellThe factor and LPS stimulate lower produce NO, IL-1 and IL-6, can suppress the mrna expression of IL-6 simultaneously, reduce NO, IL-1With the level of IL-6, part regulates osteoblastic function, has reduced the stimulation to the differentiation of osteoclast precursor Growth of CellsEffect, reduces the number of osteoclast and the bone resorption of broken bone, thereby reduces the loss of sclerotin.
Osthole has remarkable inhibitory action to oxytocin, KCl induction Isolated Rat Uterus smooth muscle contraction, to CaCl2TiredLong-pending amount effect curve is noncompetitive antagonism effect: Osthole can significantly suppress Ca in oxytocin induction dependent cells2+ShrinkReaction, to the outer Ca of dependent cells2+Contraction have no significant effect. The Osthole of 1 μ mol/L-50 μ mol/L is in vitro to rabbitThe Spontaneous Contraction amplitude of intestinal smooth muscle has obvious depression effect and is dosage compliance relation, and does not affect contraction frequency;The tetanic property of intestinal smooth muscle that the Osthole of 10 μ mol/L and 50 μ mol/L also can make exogenous Ach induce is shunk effectShould obviously weaken or eliminate; Prompting Osthole can alleviate be to a certain extent overexcited by parasympathetic nerve due to stomach and intestineThe spasm effect of smooth muscle, and main by affect that Cajal cell between duodenum longitudinal muscle and belt bone produces slowlyThe quantity that produces action potential on ripple (SW) basis is adjusted gastrointestinal dysfunction state. Above experimental result shows, snakeThe effect of the inhibition smooth muscle contraction of machine tool element, its mechanism and antagonism Ca2+Relevant, and main by suppressing smooth muscle cellVoltage-dependent Ca on film2+Passage and affect the interior Ca of born of the same parents2+Due to release.
Along with the development of modern pharmacology experiment research and technology, the pharmacological action of Osthole was constantly found in recent yearsWith deeply, also develop dissimilar novel formulation simultaneously, caused widely and paid close attention to, but really using Osthole asA kind of medicinal application is in clinical actually rare. Therefore deep clinical research, to making full use of Osthole, is opened up the traditional Chinese medical scienceNew advantage important in inhibiting in disease treatment.
At present, lysozyme and Osthole combination be there is not yet to report for the application that prevents and treats beriberi.
Summary of the invention
Technical problem to be solved by this invention is to provide one can effectively prevent and treat beriberi, have no side effect and drug resistance, and activityThe composition natural pharmaceutical composition of originating.
The present invention addresses the above problem adopted technical scheme, and a kind of pharmaceutical composition for the treatment of beriberi is provided, and wherein livesThe weight ratio of property composition lysozyme and Osthole is (1:10)～(10:1).
Preferably, in described pharmaceutical composition, the weight ratio of lysozyme and Osthole is (1:1)～(1:9).
Preferred, the weight ratio of lysozyme and Osthole is 1:4.
Preferably, described lysozyme extracts from egg.
Preferably, described pharmaceutical composition further comprises pharmaceutically acceptable auxiliary material.
Preferred, described pharmaceutically acceptable auxiliary material be selected from emulsifying agent, grease, chelating agent, hygroscopic agent, thickener,One or more in purified water;
Most preferred, described emulsifying agent is polysorbate60 or Tween 80, and grease is lanolin or vaseline, and chelating agent is second twoAmine tetraacethyl or disodium ethylene diamine tetraacetate, hygroscopic agent is talcum powder or zinc oxide, thickener be sodium carboxymethylcellulose orXanthans.
Preferably, the formulation of described pharmaceutical composition is ointment, lotion, aerosol, liniment etc.
Preferred, the formulation of described pharmaceutical composition is ointment.
The present invention also provides the application of a kind of aforementioned pharmaceutical compositions in the medicine of preparation treatment beriberi.
The present invention has actively useful effect:
Surprisingly, through repeated tests, it is right that the present invention surprisingly finds lysozyme and Osthole to be used in combinationThere is the effect of Synergistic in the control of beriberi, coordinate other active component results of use better. Compared with Western medicine preparation,Lysozyme formulation preparation method of the present invention is simple, and compatibility is reasonable, two kinds of active components in bringing into play separately effect,Can produce again synergistic function, significantly treat beriberi. Lysozyme and Osthole source are natural, and safety non-toxic, without secondaryEffect; Due in pharmaceutical composition without Western medicine antiseptic composition, therefore medicine has no drug resistance.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is further described, but embodiments of the present invention are not limited to this. FollowingThe experimental technique using in embodiment if no special instructions, is conventional method. What in embodiment and test example, use is moltenBacterium enzyme is the lysozyme extracting in egg.
Embodiment 1, preparation contain the ointment of Osthole
Weigh the Osthole of 10 weight portions, the sodium carboxymethylcellulose of 50 weight portions, the zinc oxide and 1 of 10 weight portionsThe disodium ethylene diamine tetraacetate of weight portion is scattered in the purified water of 500 weight portions, and water stirs to obtain; Weigh again 50The vaseline of weight portion, the Tween 80 of 10 weight portions, in another container, obtains oil phase after mixing; By water and oil phase differenceAfter heating, mix, the 10min that homogenizes, makes the ointment A1 that contains Osthole after cooling.
Embodiment 2, prepare the ointment of lysozyme
Weigh the lysozyme of 10 weight portions, the sodium carboxymethylcellulose of 50 weight portions, zinc oxide and 1 weight of 10 weight portionsThe disodium ethylene diamine tetraacetate of amount part is scattered in the purified water of 500 weight portions, and water stirs to obtain; Weigh again 50 weightsThe vaseline of amount part, the Tween 80 of 10 weight portions, in another container, obtains oil phase after mixing; Water and oil phase are added respectivelyAfter heat, mix, the 10min that homogenizes, makes the ointment A2 that contains lysozyme after cooling.
Embodiment 3, prepare the ointment of lysozyme and Osthole (1:1)
Weigh lysozyme, the Osthole of 5 weight portions, the sodium carboxymethylcellulose of 50 weight portions, 10 weights of 5 weight portionsThe zinc oxide of amount part and the disodium ethylene diamine tetraacetate of 1 weight portion are scattered in the purified water of 500 weight portions, stirObtain water; Weigh the vaseline of 50 weight portions, the Tween 80 of 10 weight portions, in another container, obtains oil phase after mixing again;Water and oil phase are heated respectively to rear mixing, and the 10min that homogenizes, makes after cooling and contains lysozyme and Osthole (weightAmount is than for 1:1) ointment A3.
Embodiment 4, prepare the ointment of lysozyme and Osthole (1:4)
Weigh lysozyme, the Osthole of 8 weight portions, the sodium carboxymethylcellulose of 50 weight portions, 10 weights of 2 weight portionsThe zinc oxide of amount part and the disodium ethylene diamine tetraacetate of 1 weight portion are scattered in the purified water of 500 weight portions, stirObtain water; Weigh the vaseline of 50 weight portions, the Tween 80 of 10 weight portions, in another container, obtains oil phase after mixing again;Water and oil phase are heated respectively to rear mixing, and the 10min that homogenizes, makes after cooling and contains lysozyme and Osthole (weightAmount is than for 1:4) ointment A4.
Embodiment 5, prepare the ointment of lysozyme and Osthole (1:9)
Weigh lysozyme, the Osthole of 9 weight portions, the sodium carboxymethylcellulose of 50 weight portions, 10 weights of 1 weight portionThe zinc oxide of amount part and the disodium ethylene diamine tetraacetate of 1 weight portion are scattered in the purified water of 500 weight portions, stirObtain water; Weigh the vaseline of 50 weight portions, the Tween 80 of 10 weight portions, in another container, obtains oil phase after mixing again;Water and oil phase are heated respectively to rear mixing, and the 10min that homogenizes, makes after cooling and contains lysozyme and Osthole (weightAmount is than for 1:9) ointment A5.
Test example 1, the antimycotic application of the ointment that contains lysozyme/Osthole
After Candida albicans and Trichophyton rubrum are gone down to posterity, be evenly seeded in Sharpe with getting 0.2ml after sterile saline dilutionOn plating medium, by negative control group (milk whitening hand cream), positive controls (miconazole) and trial drugGroup (embodiment 3-5 ointment) equivalent is put on flat board, between each medicine at a distance of 30mm; Flat board is put in 28 DEG C of insulating boxsCultivate; Around cover with after fungi until negative control, start to measure inhibition zone diameter, when positive control has occurred antibacterialWhen ring, judge the fungistatic effect of each trial drug, concrete antibacterially the results are shown in Table 1.
The ointment inhibition zone diameter (mm) of table 1 lysozyme and Osthole
| Candida albicans | Trichophyton rubrum | |
| Negative control group (milk whitening hand cream) | 0 | 0 |
| Positive controls (miconazole) | 28 | 26 |
| A3 (lysozyme and Osthole weight ratio are 1:1) | 27 | 27 |
| A4 (lysozyme and Osthole weight ratio are 1:4) | 30 | 28 |
| A5 (lysozyme and Osthole weight ratio are 1:9) | 28 | 27 |
Above-mentioned result of the test shows, the ointment of lysozyme and Osthole has and suppresses to do common skin pathomyceteWith, and fungistatic effect is suitable with miconazole.
Test example 2, the ointment application in beriberi in treatment that contains lysozyme/Osthole
Decortication type, vesicle and ulceration-type beriberi patient 150 (men and women half and half) are divided into 5 groups at random, and each test group is got30 patients. Before every group of patient's dispenser, clean affected part, then be coated with the embodiment 1-5 ointment by identical weight, every day 1 time, eachGroup is all used in conjunction 14 days. After drug withdrawal according to following Standard Judgement curative effect: cure---ulceration skin healing, blister disappear, extensiveMultiple normal skin; Effectively---gargalesthesia disappears, and decortication alleviates; Invalid---the state of an illness is unchanged. Add up in each group cure,Effective and invalid patient's quantity, concrete result of the test is in table 2.
Table 2 lysozyme/Osthole ointment treatment beriberi patient result
| Cure (example) | Effectively (example) | Invalid (example) | |
| A1 (Osthole) | 16 | 9 | 5 |
| A2 (lysozyme) | 10 | 12 | 8 |
| A3 (lysozyme and Osthole weight ratio are 1:1) | 21 | 7 | 2 |
| A4 (lysozyme and Osthole weight ratio are 1:4) | 26 | 4 | 0 |
| A5 (lysozyme and Osthole weight ratio are 1:9) | 19 | 8 | 3 |
Above-mentioned result of the test shows, uses patient's beriberi after the pharmaceutical composition of the present invention of various proportionings to be clearly better, and confirmsPharmaceutical composition of the present invention is to prevent and treat effect aspect beriberi remarkable. Situation about particularly remaining unchanged in active component total amountUnder, use the pharmaceutical composition (A3-A5) of lysozyme of the present invention and Osthole to use more separately lysozyme or snakeThe pharmaceutical composition (A1 and A2) of machine tool element, the cure rate of beriberi obviously improves, and proves the group of lysozyme and OstholeClose use and produced synergy, reduced the use amount of active component. Wherein lysozyme and Osthole weight ratio are 1:4Pharmaceutical composition effect the most outstanding, produced be difficult to expection excellent effect.
Claims (8)
1. a pharmaceutical composition for the treatment of beriberi, is characterized in that, wherein the weight of active component lysozyme and OstholeAmount is than being (1:10)～(10:1).
2. pharmaceutical composition according to claim 1, is characterized in that, the weight ratio of lysozyme and Osthole is(1:1)～(1:9)。
3. pharmaceutical composition according to claim 2, is characterized in that, the weight ratio of lysozyme and Osthole is1:4。
4. pharmaceutical composition according to claim 1, is characterized in that, described pharmaceutical composition further comprisesPharmaceutically acceptable auxiliary material.
5. pharmaceutical composition according to claim 4, is characterized in that, described pharmaceutically acceptable auxiliary material is selected fromOne or more in emulsifying agent, grease, chelating agent, hygroscopic agent, thickener, purified water.
6. pharmaceutical composition according to claim 5, is characterized in that, described emulsifying agent is polysorbate60 or Tween 80,Grease is lanolin or vaseline, and chelating agent is ethylenediamine tetra-acetic acid or disodium ethylene diamine tetraacetate, and hygroscopic agent is talcum powderOr zinc oxide, thickener is sodium carboxymethylcellulose or xanthans.
7. pharmaceutical composition according to claim 1, is characterized in that, the formulation of described pharmaceutical composition is ointmentAgent, lotion, aerosol, liniment etc., be preferably ointment.
8. the application of the pharmaceutical composition described in claim 1-7 any one in the medicine of preparation treatment beriberi.
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| CN108743927A (en) * | 2018-08-28 | 2018-11-06 | 湖北煜韩环境科技有限公司 | A kind of pulvis and preparation method thereof except foot odour |
| CN109464439A (en) * | 2019-01-10 | 2019-03-15 | 吉林大学 | Osthole is preparing the application in MCR-1 enzyme inhibitor |
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