CN105688197A - Beriberi treatment drug containing lysozyme - Google Patents

Abstract

The invention relates to pharmaceutical composition for treating beriberi. An active ingredient lysozyme and an active ingredient curcumin in the pharmaceutical composition are in a weight ratio being (1:10)-(10:1). Compared with a common Western medicine preparation, the lysozyme preparation adopts a simple preparation method, the compatibility of medicines is reasonable, the two active ingredients can produce synergistic interaction while respective functions are performed, and beriberi is treated remarkably. The lysozyme and the curcumin are naturally sourced, are safe and have no toxic and side effects; the pharmaceutical composition is free of an ingredient of a Western medicine antibacterial agent, so that the drug does not have drug resistance.

Description

The treatment beriberi of lysozyme

Technical field

The present invention relates to pharmaceutical field, be specifically related to a kind of medicine treating beriberi。

Background technology

Beriberi medically also known as " tinea pedis ", is commonly called as " tinea pedis ", is foot fungus infection。Show as between toe or vola skin pruritus, erythema, pimple, decortication, or have blister, seriously can be rotten to the corn, ooze out。As control can involve other positions not in time, cause tinea corporis, tinea cruris or " tinea unguium "。Medically generally beriberi is divided three types: erosive type, vesicle, keratinization type beriberi。Erosive type is apt to occur in the 3rd and the 4th, between the 4th and the 5th toe。From the beginning of between toe moist, dipping turns white or plays phlysis, after dry desquamation, peel off scurf be moisten, the rotten to the corn face of flushing, odd itch, easy secondary infection。Vesicle is apt to occur in sufficient edge。From the beginning of the phlysis full for wall thickness, the be fused into bulla having, bleb liquid is transparent, around without blush。Conscious very itch, after scratching, often cause erysipelas, lymphangitis etc. because of secondary infection。Keratinization type is apt to occur in heel。Main manifestations is that skin is slightly thick to be dried, and keratinization desquamation, scratches where it itches, and easily chaps。This type is without vesicle and suppuration, and the course of disease is slow, does not heal for many years。

Can being divided into three types according to beriberi, Therapeutic Method is also different because of type。Keratinization drying type patient, medication should based on cream, unguentum；If blister wastes the patient of rotten type, namely affected part infiltration, should first process more dry by affected part, then treat with medicine powder again；Also having a class patient to belong to mixed type, the position namely having dries, peels, and rotten flowing water is wasted at some positions, now just should medication as the case may be。Except distinguishing type medication, patient also should pedicure journey medication under the guidance of doctor。Often treating with antifungal drug, conventional product has daktarin, Lamisil, Pevisone, PIKANGWANG and ZUGUANG SAN etc.。

Clinical pharmacology research shows, medication nitrofural 0.5g, boric acid 5g, benzoic acid 5g, salicylic acid 5g, tannic acid 5g, treats beriberi after grinding into powder, and the cure rate to 191 example patient treatments is 99.48%。Use atropine 1.2g, nystatin 5*10⁶U, aspirin 1.5g, Radix Sophorae Flavescentis 5g, Herba Senecionis Scandentis 5g, Pulvis Talci 5g。Each medicine is ground into powder above, mix homogeneously, and every day, after noon, foot bath in night are dried, takes appropriate medicated powder and is spread on affected part, treat patient 154 example, 98 examples of fully recovering, effective 42 examples, effective 14 examples。31 examples are cured 3 months state of an illness and are again recurred, through again with medicine-feeding treatment recovery from illness, total effective rate 100%。Take benzoic acid, salicylic acid, Realgar mix homogeneously, cross 60 mesh sieves, often wrap 30g, medicine one bag is put into 750g vinegar, stirs evenly and treat that big portion dissolves。Affected part is saturating with Warm Wash, removes Lao Pi, dries, immerses more than 1h in above-mentioned medicinal liquid, dry。Verify that permeability is strong through clinical observation, persistent, easy to use, evident in efficacy。With warm water foam washing biped, take 75% cotton ball soaked in alcohol after drying and repeatedly embrocate affected part, 1 time every night, footwear are cleaned up simultaneously, after drying, take in 75% cotton ball soaked in alcohol wiping footwear。This group all obtains effect through treating, pruritus and Schultz-Charlton。Wherein 1 person of being cured 22 example, 2 person of being cured 9 examples。Following up a case by regular visits to recurrence in the shortest 3 months, recurrent cases continues and still can cure by this law。

In recent years, there are some researches show acupuncture and the equally possible treatment beriberi of laser therapy。Take Ipsilateral tsu san li, SANYINJIAO acupoint, routine disinfection。Patient lies supine position, with No. 28 2 cun of acupuncture needles, first acupuncture sp 6, pin sense is conducted downwards, shank is upwards twitched 2 times, then acupuncture at Zusanli again, and pin sense is preferred to foot conduction, thrusts straightly 1 cun-15 cun, let the acupuncture needle remain at a certain point, and 30min, interval 10min handle the needle 1 time, every day 1 time, 5 statistics curative effects。Treat in 48 examples, 43 examples of fully recovering, account for 89.58%；Effective 5 examples, account for 10.42%, total effective rate 100%。Adopt the multi-functional CO of DJZ-B type₂Laser therapy aparatus, power 30W-50W, continuously adjustabe, suffer from after foot channel crosses and disinfect, use CO₂Laser physical therapy camera lens is from wound surface 3cm-5cm, rotary irradiation, and the time is 15min-20min, once a day, dry incrustation after 3d-5d, various transference cures and fully recover。

At present, the medicine for treating beriberi is mainly Western medicine antibacterial on the market, and life-time service easily produces drug resistance。Therefore, it is necessary to research and develop a kind of medicine replacement antibacterial use natural, that have no side effect, have no drug resistance of originating。

Lysozyme (lysozyme) also known as muramidase (muramidase) or N-acetylmuramide lycanohydrlase (N-acetylmuramideglycanohydrlase), is a kind of alkaline enzyme that can be hydrolyzed in pathogenic bacterium mucopolysaccharide。Mainly through destroying the β-Isosorbide-5-Nitrae glycosidic bond between-acetylmuramic acid and the NAG in cell wall, make the insoluble mucopolysaccharide of cell wall resolve into solubility glycopeptide, cause that the effusion of cell wall rupture content makes bacterolysis。Lysozyme also can with electronegative virus protein directly in conjunction with, with DNA, RNA, apoprotein formed double salt, make virally inactivated。Therefore, this enzyme has the effects such as antibacterial, antiinflammatory, antiviral。Lysozyme (also referred to as lyase) is a molecular weight is the enzyme of 14.4kDa, it can pass through in catalysis Peptidoglycan between-acetylmuramic acid and 2-Acetamido-2-deoxy-D-glucose residue and in chitodextrin between N-acetyl-glucosamine residue 1, the hydrolysis of 4-β chain, and destroy the cell wall of antibacterial。In human body, lysozyme, at emiocytosis liquid, is widely present in saliva, tear and some other body fluid；Exist in the cytoplasmic granule body in mitochondrion。Additionally, Ovum Gallus domesticus album also has substantial amounts of lysozyme。Lysozyme, because of the alkali hydrolysising protease of the cell wall acting on purpose microorganism that can be single-minded, is applied to the industries such as food, feedstuff, 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。When pH value is acute variation in 1.2～11.3 scopes, its structure is almost constant。In sour environment, lysozyme is very strong to the stability of heat；When pH value is 4～7,100 DEG C of process 1min remain to keep original enzyme activity；When pH value is 3 resistant to 100 DEG C of heat treated 45min；In dry conditions, lysozyme can be deposited in room temperature for a long time, and its sterling is white or slightly yellow。The crystalline solid of yellow or amorphous powder, odorless, taste is sweet。Soluble in water, suffer alkali destructible, insoluble in acetone and ether。As medical supplies, lysozyme has good biocompatibility, to organizing the advantage such as non-stimulated, avirulence。

Lysozyme is widely present in poultry, the Ovum Gallus domesticus album of birds and mammiferous tear, saliva, blood plasma, urine, milk, leukocyte and other body fluid and tissue (such as liver, kidney) cell；Also lysozyme can be isolated, wherein with content in Ovum Gallus domesticus album for the highest (containing about 0.3%) from Fructus Hordei Vulgaris, Fructus Fici, Fructus Chaenomelis and the plant such as Brassica oleracea L.var.capitata L., Radix Raphani。And the lysozyme activity in human milk, tear, saliva is far above (being about 3 times) in Ovum Gallus domesticus album or the activity of the lysozyme in other sources。Lysozyme in Ovum Gallus domesticus album is the Typical Representative of animal lysozyme, is object of study important in lysozyme group, is also it is currently understood that the most clearly one of lysozyme。In mammiferous milk, the lysozyme content in lacto is 3000 times of Lac Bovis seu Bubali。By sources different, lysozyme can be divided into lysozyme that egg white lysozyme, animal lysozyme, plant lysozyme, microorganism produce and the lysozyme that bacteriophage produces；Different by function cells wall, lysozyme can be divided into bacteria cell wall lysozyme and fungal cell wall lysozyme。

Lysozyme can the cell wall of single-minded cracking purpose antibacterial。Its main attack Peptidoglycan, hydrolysis connects the β-Isosorbide-5-Nitrae glycosidic bond of-acetylmuramic acid and the 4th carbon atom of N-acetyl-glucosamine。Whole process is, first lysozyme is attached on Peptidoglycan molecule by " ditch " between two domain；Its substrate forms the conformation of transition state in enzyme subsequently。According to Phillips mechanism, lysozyme is combined with glucohexaose。Then the 4th sugar distortion on glucohexaose is half-chair conformation by lysozyme。In this twisted state (energy is higher), glycosidic bond is easy for rupturing。The side chain being positioned at the glutamic acid (Glu35) of antalzyme protein sequence 35 and the aspartic acid (Asp52) of 52 is very crucial to the activity of lysozyme。Glu35, as the proton donor of glycosidic bond, shears the C-O key of substrate；And Asp52 participates in generating glycosyl enzyme intermediate as nucleopilic reagent。Subsequently, glycosyl enzyme intermediate and hydrone react, and hydrolysis generates product, and enzyme remains unchanged。

The extracting method of lysozyme includes following several: 1, direct crystallization method: this method is simple to operate, and cost is low, but can not in order to separate the lysozyme of trace。2, ion exchange chromatography: this method have simplicity, efficiently, cost low, and can the advantage circle of automatization's continuous operation。3, affinity chromatograph: the multiple of affinity chromatography separation purification is higher, quality is better, and can be widely applied to the lysozyme in various source, for concentrating and the lysozyme of refining trace。But owing to the making of affinity adsorbent is more complicated, limit its extensive utilization industrially。4, ultrafiltration is combined with affinity chromatograph: ultrafiltration is combined extraction lysozyme with affinity chromatograph, is the new method developed in recent years。First removing major part foreign protein with ultrafiltration, retain lysozyme, now lysozyme is also relatively thick, then obtains purified product with affinity chromatography。5, membrane chromatography technology: late 1980s, occurs in that affinity film chromatography technology。This technology has membrance separation and the affine feature separated concurrently。Compared with traditional membrance separation, affinity chromatography; membrane chromatography technology not only has purification height, pressure drop is little, disengaging time is short, biomacromolecule degeneration probability in separation process is little; and allow the feature such as charging rate faster, and it is more easy to than post affinity chromatography and accomplishes scale production。6, ultrafiltration: compared with traditional bio-chemistry separation technology, hyperfiltration technique is a major advantage that the high yield output of product。Although but hyperfiltration technique is widely used in the process such as reverse osmosis and concentration, but as the very big a kind of protein stripping technique of potential in biological industry field, ultrafiltration is fully utilized not yet。7, reverse micelle extracts: reverse micelle extraction is a kind of new extracting process that developed recently gets up, it is the method utilizing the reverse micelle adding the formation of a small amount of surfactant in organic solvent to extract, open up a kind of new isolation technics for some bioactive substances such as the enzyme that can not use organic solvent extraction and reactive protein, expand the scope of application of organic solvent extraction。8, bioseparation technology: the bioseparation technology (immobilized metal affinity chromatography, affinity precipitation, affinity filtration method) based on affinity, is also one of lysozyme extracting method。

Lysozyme has multiple uniqueness and important pharmacological action。

First, anti-inflammation。The cell wall of antibacterial is made up of murein, the polymer that murein is alternately made up of 2-Acetamido-2-deoxy-D-glucose and-acetylmuramic acid, on cell wall residue can connecting peptides, be called Peptidoglycan。Polysaccharide exists with linear form, can be connected with each other by peptide chain part, thus forming three dimensional structure between polysaccharide chain located adjacent one another。Lysozyme acts on the glycosidic bond between the-acetylmuramic acid of Peptidoglycan molecule and N-acetyl glucosamine ammonia in specific manner, and result makes bacteria cell wall become loose, loses the protective effect to cell, and last cytolysis is dead；Lysozyme can directly kill gram positive bacteria, in the presence of S-IgA complement, moreover it is possible to kills gram-negative bacteria: such as colon bacillus。Lysozyme also can be combined with the various acidic materials bringing out inflammation, reduces bacterial endotoxin release, occurs thus alleviating endotoxemia, slow down inflammation generating process, and antibiosis is have certain potentiation, improve the mucopolysaccharide metabolism of periplast, play the effect of anti-inflammation, repair tissue。Tests prove that, with a kind of cellulose copolymer by human lysozyme and proteolytic enzyme coupling, be remarkably improved lysozyme antibiotic ability, accelerating wound healing。

Second, antiviral。Lysozyme with a large amount of positive charges, directly can act on the virus protein with negative charge under neutral fluid environment, and combine formation double salt with DNA, RNA, desorption base albumen, makes virally inactivated。Suppression cytopathy effect is had after adding lysozyme in by the Hela cell culture fluid of herpesvirus infection。Lysozyme also can suppress adenovirus to grow, and can be used for the viral illness treatments such as herpes zoster, parotitis, chicken chickenpox, hepatitis and influenza。

3rd, enhancing immunity。Lysozyme participates in panimmunity reaction in body, has important function in body normal defense and nonspecific immunity。It can improve and strengthen macrophage phagocytic digestive function, reduces the leukopenia that cytostatics causes, in conjunction with bacteria lipopolysaccharide, alleviates endotoxin effect, to reach the purpose of enhancing body resistance。Lysozyme itself has t cell epitope, and 2 types (Th2) t helper cell can be induced to react。Oral lysozyme energy inducing mouse produces general Th1 and Th2 immunoreation, strengthens immunologic function, and therefore, oral lysozyme has the function controlling upper respiratory tract infection and treatment dysentery。Additionally, lysozyme also has the hematoblastic function of activation, tissue local disturbance of blood circulation can be improved, decompose pus, strengthen local defense function, thus embodying its hemostasis, detumescence and accelerating the repair of body injury tissue。It is alternatively arranged as a kind of host's resistance factor, and tissue local is shielded。

Scientific research personnel have accumulated a large amount of experiences of lysozyme application in clinical trial。Such as, drug sensitive test, with composite lysozyme, fluconazol and 3 kinds of medicines of nystatin for trial drug, studies the fungistatic effect of they Candida albicans to separating, and adopts NCCLSM27-A micro-dilution method to measure the MIC value of medicine。The Fungus antifungal susceptibility of three kinds of medicines shows: composite lysozyme, fluconazol and nystatin are for minimal inhibitory concentration respectively 2.03 μ g/ml, the 3.19 μ g/ml and 6.03 μ g/ml of separated Candida albicans；Candida albicans to the sensitivity of composite lysozyme more than fluconazol and nystatin；Clinical observation on the therapeutic effect research shows: the effective percentage of composite lysozyme treatment children's's oral candidiasis is 97.5%, hence it is evident that higher than comparison nystatin group；The treatment time average out to 6.46d of composite lysozyme group, hence it is evident that lower than the 13.0d of comparison nystatin group；Its result of study shows: Candida albicans is the highest to the sensitivity of composite lysozyme, more than fluconazol and nystatin。Composite lysozyme is used for treating children's's thrush, short treating period, and cure rate is high。The external drug sensitivity tests of antifungal of composite lysozyme is consistent with clinical efficacy, it was shown that drug susceptibility and clinical efficacy exist certain dependency。Separately there are some researches show, children's acute sinusitis is under the auxiliary of lysozyme, and symptom rapidly disappears at about 14d, and nasal mucosa recovers normal, and the children's acute sinusitis healing time of matched group is considerably longer than seminar, and display lysozyme has assists antibacterial functions efficiently；Seminar and matched group are respectively provided with significant difference in cure rate with obvious effective rate, it was demonstrated that lysozyme has and dramatically speeds up children's acute sinusitis recovery from illness speed, and not yet finds untoward reaction, has certain clinic popularization and application values。Owing to prevention and the treatment of diseases of the five sense organs are had good curative effect by lysozyme, domestic at present have lysozyme buccal tablet to list, and lysozyme has broad application prospects at treatment diseases of the five sense organs。

Curcumin (curcumin) is the polyphenols that a kind of relative molecular mass extracted from zingiberaceous plant CurcumalongaL. is little, it is generally recognized that it is the most effective composition in Rhizoma Curcumae Longae, containing 2%～8% in most of Rhizoma Curcumae Longae preparations。The research history of Rhizoma Curcumae Longae is long, and Ayurvedic medicine is thought by modern medicine term, and turmeric powder can treat gallbladder illness, anorexia, rhinitis, cough, diabetes, liver illness, rheumatism and sinusitis。China's traditional medicine is thought, the treatment of the relevant disease such as Rhizoma Curcumae Longae can be used for suffering from abdominal pain, jaundice。Substantial amounts of research in recent years proves, curcumin has antioxidation, antiinflammatory, anticancer, scavenging free radicals, antimicrobial and to many-sided pharmacological action such as cardiovascular system, digestive system。Curcumin toxicity is low, untoward reaction is little, medicine source is wide, inexpensive, taking convenience, therefore has wide using value and development prospect clinically。

In active chronic inflammation, curcumin can play good protective action in vivo。When inflammation occurs, curcumin can suppress to produce the activity of reactive oxygen species enzyme, such as lipoxidase (LOX), Cycloxygenase (COX), xanthine dehydrogenase and nitric oxide synthase type (iNOS)。Curcumin can suppress the generation of the nitrogen oxides of lipopolysaccharide in macrophage (LPS) and interferon (INF)-γ induction, the expression of the c-jun gene in the activity of protein kinase and fibroblast。Curcumin can suppress the expression of scytitis and relevant c-Fos, c-Jun gene and the formation of hydrogen peroxide。Anti-inflammatory property in view of curcumin, it is possible to for treating the various disease caused because of inflammation, its Therapy study in autoimmune disease is interesting in recent years。Curcumin is by regulating various inflammatory cytokine, as IL-1 β, IL-6, IL-12, TNF-α, IFN-γ and NF-κ B etc. improve the symptom of the diseases such as rheumatic arthritis, inflammatory bowel disease, type 1 diabetes, myocarditis, whole body system lupus erythematosus。

Most research in nearly 20 years proves that curcumin has multiple action target spot in the process suppressing the transfer of tumor cell, hypertrophy and infiltration, further illustrates its therapeutical effect to tumor。Curcumin can suppress some tumor cell lines to include the growth of cell strain of drug resistance；The expression of the cyclin D1 of multiple secretion can be suppressed。Cyclin D1 includes cell cycle protein dependent kinase Cdk4 and Cdk6, can limit the growth of cell at cell cycle。Curcumin can also carry out the apoptosis of inducing tumor cell by activating caspase-8, thus causing that Bid cracks, successive stimulus mitochondrion release cells pigment C, activates caspase-9 and caspase-3, activates the apoptosis of Poly ADP-ribose polymerase and inducing tumor cell further。Curcumin can also suppress the activation of some oncogenic transcription factor, such as NF-κ B, AP-1, signal transducer and activated transcription albumen (STAT3, STAT5), and can regulate the expression of Egr-1, PPAR-γ, β catenin and Nrf-2。Simultaneously, curcumin can regulate the expression of the propagation of tumor cell, intrusion, transfer, angiogenesis and the anti-chemotherapy factor, reduces the expression of Bc1-2, Bc1XL, cyclooxygenase 2, Matrix Metalloproteinase-9, tumor necrosis factor, cyclin D1 and adhesion molecule。Substantial amounts of zoopery proves that kinds of tumors is had effective chemopreventive activity by curcumin。Prove that curcumin can effectively prevent and treat cancer from front and clinical research external, internal, clinical。

Having bibliographical information, 10 μm of ol curcumins can cause active oxygen in rat peritoneal macrophages to reduce, and the curcumin of similar concentration also can produce similar effect in erythrocyte。More it should be noted that and studies have found that curcumin has the effect removing peroxide。The antioxidation of curcumin is closely related with the chemical constitution of its uniqueness: curcumin is made up of two methylated phenol of neighbour and a beta-diketon, wherein phenolic hydroxyl group can be caught or scavenging free radicals, this ability seems under the existence of methoxyl group and becomes apparent from, therefore, curcumin is considered as a kind of natural antioxidant。SOD and GSH-Px is the internal two kinds of antioxidases being widely present, and belongs to enzymatic Free-radical ring opening polymerization。The impact that the microglia induction type iNOS that lipopolysaccharide is activated by research curcumin expresses, result shows that 20 μm of ol/L curcumins can be effectively improved the activity of cell SOD and GSH-Px, has the ability of scavenging activated oxygen, lipid peroxide。

Compared with other pharmacological action, curcumin antimicrobial effect report is less。Research finds that curcumin can suppress HIV (human immunodeficiency virus) long terminal repeat activity, it is suppressed that the relevant enzyme of virus replication and cytokine is had impact。HIV-1 and HIV-2 is all had inhibitory action by curcumin。The external effect to influenza A H1N1 hypotype, H3N2 subtype virus of curcumin is observed by Madin-Darby canine kidney(cell line) (MDCK)。Test result indicate that, curcumin has resisiting influenza virus to be replicated and direct virus-killing action, mechanism of action is likely to suppress influenza virus envelopes function, impact virus to the absorption of sensitive cells and to penetrate closely related with it, can not only direct inactivation of viruses, to being adsorbed in cell surface and entering intracellular virus and also have inhibitory action。But its interior resisting virus effect is still needed and is further characterized by。

At present, the combination of lysozyme and curcumin is used for preventing and treating the application of beriberi, and there is not been reported。

Summary of the invention

The technical problem to be solved is to provide one can effectively prevent and treat beriberi, has no side effect and drug resistance, the pharmaceutical composition that active component source is natural。

This invention address that the problems referred to above be employed technical scheme comprise that, it is provided that a kind of pharmaceutical composition treating beriberi, wherein the weight ratio of active component lysozyme and curcumin is (1:10)～(10:1)。

Preferably, in described pharmaceutical composition, the weight ratio of lysozyme and curcumin is (1:1)～(1:9)。

It is furthermore preferred that the weight ratio of lysozyme and curcumin is 1:4。

Preferably, described lysozyme extracts from Ovum Gallus domesticus album。

Preferably, described pharmaceutical composition farther includes pharmaceutically acceptable adjuvant。

It is furthermore preferred that described pharmaceutically acceptable adjuvant is selected from one or more in emulsifying agent, oils and fats, chelating agen, hygroscopic agent, thickening agent, purified water；

Most preferred, described emulsifying agent is polysorbate60 or Tween 80, and oils and fats is lanoline or vaseline, and chelating agen is ethylenediaminetetraacetic acid or disodiumedetate, and hygroscopic agent is Pulvis Talci or zinc oxide, and thickening agent is sodium carboxymethyl cellulose or xanthan gum。

Preferably, the dosage form of described pharmaceutical composition is ointment, lotion, aerosol, liniment etc.。

It is furthermore preferred that the dosage form of described pharmaceutical composition is ointment。

The present invention also provides for the application in the medicine of preparation treatment beriberi of a kind of aforementioned pharmaceutical compositions。

The invention have the advantages that:

It is surprising that through repeated tests, present inventors have unexpectedly found that and use the preventing and treating for beriberi to have the effect of Synergistic with curcumin combination lysozyme, coordinate other active component results of use more preferably。Compared with Western medicine preparation, the lysozyme formulation preparation method of the present invention is simple, and compatibility is reasonable, and two kinds of active component, while playing respective effect, can produce again synergistic function, significantly treat beriberi。Lysozyme and curcumin source are natural, and safety non-toxic has no side effect；Due in pharmaceutical composition without Western medicine antibacterial 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。The experimental technique used in following embodiment if no special instructions, is conventional method。The lysozyme used in embodiment and test example is the lysozyme extracting from Ovum Gallus domesticus album。

Embodiment 1, the preparation ointment containing curcumin

Weighing the curcumin of 10 weight portions, the sodium carboxymethyl cellulose of 50 weight portions, the zinc oxide of 10 weight portions and the disodiumedetate of 1 weight portion to be scattered in the purified water of 500 weight portions, stir to obtain aqueous phase；Weighing the vaseline of 50 weight portions again, the Tween 80 of 10 weight portions, in another container, obtains oil phase after mixing；Mixing after aqueous phase and oil phase being heated respectively, homogenize 10min, makes the ointment A1 containing curcumin after cooling。

Embodiment 2, prepare the ointment of lysozyme

Weighing the lysozyme of 10 weight portions, the sodium carboxymethyl cellulose of 50 weight portions, the zinc oxide of 10 weight portions and the disodiumedetate of 1 weight portion to be scattered in the purified water of 500 weight portions, stir to obtain aqueous phase；Weighing the vaseline of 50 weight portions again, the Tween 80 of 10 weight portions, in another container, obtains oil phase after mixing；Mixing after aqueous phase and oil phase being heated respectively, homogenize 10min, makes the ointment A2 containing lysozyme after cooling。

Embodiment 3, prepare lysozyme and the ointment of curcumin (1:1)

Weighing the lysozyme of 5 weight portions, the curcumin of 5 weight portions, the sodium carboxymethyl cellulose of 50 weight portions, the zinc oxide of 10 weight portions and the disodiumedetate of 1 weight portion to be scattered in the purified water of 500 weight portions, stir to obtain aqueous phase；Weighing the vaseline of 50 weight portions again, the Tween 80 of 10 weight portions, in another container, obtains oil phase after mixing；Mixing after aqueous phase and oil phase being heated respectively, homogenize 10min, makes the ointment A3 containing lysozyme and curcumin (weight ratio is 1:1) after cooling。

Embodiment 4, prepare lysozyme and the ointment of curcumin (1:4)

Weighing the lysozyme of 2 weight portions, the curcumin of 8 weight portions, the sodium carboxymethyl cellulose of 50 weight portions, the zinc oxide of 10 weight portions and the disodiumedetate of 1 weight portion to be scattered in the purified water of 500 weight portions, stir to obtain aqueous phase；Weighing the vaseline of 50 weight portions again, the Tween 80 of 10 weight portions, in another container, obtains oil phase after mixing；Mixing after aqueous phase and oil phase being heated respectively, homogenize 10min, makes the ointment A4 containing lysozyme and curcumin (weight ratio is 1:4) after cooling。

Embodiment 5, prepare lysozyme and the ointment of curcumin (1:9)

Weighing the lysozyme of 1 weight portion, the curcumin of 9 weight portions, the sodium carboxymethyl cellulose of 50 weight portions, the zinc oxide of 10 weight portions and the disodiumedetate of 1 weight portion to be scattered in the purified water of 500 weight portions, stir to obtain aqueous phase；Weighing the vaseline of 50 weight portions again, the Tween 80 of 10 weight portions, in another container, obtains oil phase after mixing；Mixing after aqueous phase and oil phase being heated respectively, homogenize 10min, makes the ointment A5 containing lysozyme and curcumin (weight ratio is 1:9) after cooling。

Test example 1, containing lysozyme/curcumin ointment antifungal application

After trichophyton gypseum and acrothesium floccosum are gone down to posterity, take 0.2ml after diluting with sterile saline and be uniformly seeded on Sharpe plating medium, negative control group (milk whitening hand cream), positive controls (miconazole) and trial drug group (embodiment 3-5 ointment) equivalent are put on flat board, at a distance of 30mm between each medicine；Flat board is put in 28 DEG C of calorstats and cultivate；After covering with fungus around negative control, starting to measure inhibition zone diameter, judge the fungistatic effect of each trial drug when positive control occurs antibacterial ring, concrete antibacterial result is in Table 1。

The ointment inhibition zone diameter (mm) of table 1 lysozyme and curcumin

	Trichophyton gypseum	Acrothesium floccosum
			Negative control group (milk whitening hand cream)	0	0
Positive controls (miconazole)	26	27
			A3 (lysozyme and curcumin weight ratio are 1:1)	28	28
A4 (lysozyme and curcumin weight ratio are 1:4)	30	29
			A5 (lysozyme and curcumin weight ratio are 1:9)	27	29

Above-mentioned result of the test shows, common skin pathomycete is had an inhibitory action by the ointment of lysozyme and curcumin, and fungistatic effect and miconazole suitable。

The application in treatment beriberi of test example 2, ointment containing lysozyme/curcumin

Decortication type, vesicle and ulceration-type beriberi patient 150 (men and women half and half) are randomly divided into 5 groups, and each test group takes 30 patients。Often cleaning affected part before group patient administration, repaste the embodiment 1-5 ointment using identical weight, every day 1 time, each group is all used in conjunction 14 days。According to following Standard Judgement curative effect after drug withdrawal: cure ulceration skin healing, vesicle disappears, and recovers normal skin；Effective gargalesthesia disappears, and decortication alleviates；The invalid state of an illness is unchanged。Adding up in each group and cure, effectively and the quantity of refractory patient, concrete result of the test is in Table 2。

Table 2 lysozyme/curcumin ointment treatment beriberi patient's result

	Cure (example)	Effectively (example)	Invalid (example)
				A1 (curcumin)	10	14	6
A2 (lysozyme)	11	12	7
				A3 (lysozyme and curcumin weight ratio are 1:1)	18	9	3
A4 (lysozyme and curcumin weight ratio are 1:4)	25	5	0
				A5 (lysozyme and curcumin weight ratio are 1:9)	20	8	2

Above-mentioned result of the test shows, after using the pharmaceutical composition of the present invention of various proportioning, the beriberi of patient is clearly better, it was demonstrated that the pharmaceutical composition of the present invention effect in preventing and treating beriberi is notable。Particularly when active component total amount remains unchanged, the pharmaceutical composition (A3-A5) using lysozyme of the present invention and curcumin is relatively used alone the pharmaceutical composition (A1 and A2) of lysozyme or curcumin, the cure rate of beriberi significantly improves, proving that the combination of lysozyme and curcumin uses and create synergy, what decrease active component makes consumption。Wherein lysozyme and curcumin weight ratio are that the pharmaceutical composition effect of 1:4 is the most prominent, create and are difficult to intended excellent effect。

Claims (8)

1. the pharmaceutical composition treating beriberi, it is characterised in that wherein the weight ratio of active component lysozyme and curcumin is (1:10)～(10:1)。

2. pharmaceutical composition according to claim 1, it is characterised in that the weight ratio of lysozyme and curcumin is (1:1)～(1:9)。

3. pharmaceutical composition according to claim 2, it is characterised in that the weight ratio of lysozyme and curcumin is 1:4。

4. pharmaceutical composition according to claim 1, it is characterised in that described pharmaceutical composition farther includes pharmaceutically acceptable adjuvant。

5. pharmaceutical composition according to claim 4, it is characterised in that described pharmaceutically acceptable adjuvant is selected from one or more in emulsifying agent, oils and fats, chelating agen, hygroscopic agent, thickening agent, purified water。

6. pharmaceutical composition according to claim 5, it is characterized in that, described emulsifying agent is polysorbate60 or Tween 80, oils and fats is lanoline or vaseline, chelating agen is ethylenediaminetetraacetic acid or disodiumedetate, hygroscopic agent is Pulvis Talci or zinc oxide, and thickening agent is sodium carboxymethyl cellulose or xanthan gum。

7. pharmaceutical composition according to claim 1, it is characterised in that the dosage form of described pharmaceutical composition is ointment, lotion, aerosol, liniment etc., it is preferred to ointment。

8. the application in the medicine of preparation treatment beriberi of the pharmaceutical composition described in any one of claim 1-7。