CN101032482A - Compound preparation resisting coxsackie virus and herpesvirus - Google Patents
Compound preparation resisting coxsackie virus and herpesvirus Download PDFInfo
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- CN101032482A CN101032482A CN 200610125582 CN200610125582A CN101032482A CN 101032482 A CN101032482 A CN 101032482A CN 200610125582 CN200610125582 CN 200610125582 CN 200610125582 A CN200610125582 A CN 200610125582A CN 101032482 A CN101032482 A CN 101032482A
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- herpesvirus
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- emodin
- coxsackie virus
- curcumin
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Abstract
The present invention is one kind of compound preparation for antagonizing Coxsackie virus and herpes virus. The compound preparation includes emodin, total matrine and total curcumin in certain weight proportion as well as supplementary materials. The compound preparation has high effects of suppressing and killing Coxsackie virus and herpes virus.
Description
Technical field
The invention belongs to field of traditional Chinese medicine pharmacy, be specifically related to the compound preparation of a kind of resisting coxsackie virus and herpesvirus.This compound preparation is made up of a certain proportion of emodin, Radix Sophorae Flavescentis total alkaloids and Rhizoma Curcumae Longae total pigment.
Background technology
The intestinal poison that Coxsackie virus (Coxsackie virus) belongs to Picornaviridae belongs to, in the crowd, infect very general, with multiple human diseases very confidential relation is arranged, as viral myocarditis, chronic pancreatitis, chronic fatigue syndrome, chronic nephritis, arrhythmia, type i diabetes etc.According to statistics, the annual myocarditis prevalence in the whole world is 5～8/100,000, and 25%～50% acute pericarditis patient, 36%～65% acute myocarditis patient have in the recent period or the CVB of recurrence infects.Because lack effective medicine, many patients are developed into chronic DCM (dilated cardiomyopathy), die from heart failure at last.
The human simple herpesvirus is divided into amphitypy, i.e. herpes simplex virus I-type (HSV-I) and herpes simplex virus I I type (HSV-II).The HSV-I type mainly causes the infection of skin, mucosa (oral mucosa) and organ (brain) beyond the genitals.The HSV-II type mainly causes the genital area mucocutaneous infections.Genital herpes is the disease that spreads through sex intercourse that is mainly caused by HSV-II, and herpesvirus is present in the transudate, seminal fluid, prostate juice, cervix uteri, vaginal secretion of skin and mucosal injury, mainly infects by sexual intercourse, causes primary genitalia herpes.After primary genitalia herpes disappears, remaining virus is hidden in the hiding in sacral ganglia along the neuraxon for a long time through peripheral nerve, when Abwehrkraft des Koepers reduce or some motivating factor as generate heat, suffer from cold, effects such as infection, menstruation, gastrointestinal dysfunction, wound time, can make the activated viral of hiding in the body and recur.Primary disease sickness rate height can infect neonate by Placenta Hominis and birth canal, cause miscarriage and neonatal death, and is also relevant with the generation of cervical cancer, endangers greatlyyer, do not have specific short again, is subject to people's attention.Therefore, genital herpes has been classified as one of 8 kinds of sexually transmitted disease (STD)s of keypoint control by Ministry of Public Health.
Emodin (emodin) chemistry is called 1,3, and 8-trihydroxy-6 tectoquinone, molecular weight are 270.23.The emodin effect is very extensive: combine with effect organ's muscle protein and show cholinergic effect, suppress moisture to be transported to cell from enteric cavity, make moisture retention at enteric cavity, thereby stimulate large intestine and be beneficial to defecation; Serum hyaluronic acid and laminin are significantly reduced, and the liver tissue fibrosis degree is obviously improved, and hepatocyte injury alleviates; Pancreas kallikrein, trypsin etc. be can suppress, the regeneration and the reparation of pancreatic tissue participated in; Can suppress the inductive vasoconstriction reaction of histamine; Can suppress the inductive Cavia porcellus thoracic aortic ring of phyenlephrinium vasoconstriction reaction; Vascular smooth muscle cell proliferation also there is inhibitory action; The activity of stronger competitive inhibition renal medulla Na+-K+-ATP enzyme is arranged, thereby play diuresis; Can promote the apoptosis of people's squamous cell lung carcinoma cell and people's lung non-small cell cancerous cell, human mouth squamous cell carcinoma and salivary gland tumor cell are had stronger cytotoxicity; Can suppress the excretory TNF-a of rat abdominal cavity macrophage that lipopolysaccharide stimulates; Can inflammation-inhibiting in the reaction NO a large amount of synthetic and discharge; Have significant antibacterial action, all effective to staphylococcus aureus, escherichia coli, dysentery bacterium, streptococcus, streptococcus pneumoniae, helicobacter pylori etc.; Also has antiviral preferably effect.
Curcumin (curcumin) is a kind of natural and organic ingredients that extracts from rhizomes such as Zingiberaceae curcuma Rhizoma Curcumae Longae, Rhizoma Curcumae, Radix Curcumae, has multiple pharmacological effect such as antitumor, antiinflammatory, antibiotic, antioxidation.Curcumin is all inhibited to generation, propagation, the transfer of the cancerous cell of kinds of tumors such as colon cancer, gastric cancer, hepatocarcinoma, breast carcinoma, carcinoma of prostate, skin carcinoma, leukemia etc., inducing apoptosis of tumour cell; Can stop the mispairing reparation of rectum oncocyte DNA, can hinder the invasion and attack of tumorigenesis factor, reach its anti-tumor effect by activity and the raising glutathione invertase that suppresses cytochrome P 450 enzymes; Can to acute, subacute, chronic inflammatory disease inhibitory action be arranged all by infiltration, inhibition lipid peroxidation, the active inflammatory reaction that suppresses colon cell of reduction serine that reduces neutrophilic granulocyte; Phenolic hydroxyl group in the curcumin molecule makes it have stronger antioxidation, can suppress peroxidization, the cholesterol reducing of lipid, and important organs such as mouse brain, the heart, liver,kidney,spleen are all had very significantly antioxidation; Curcumin also has immunosuppressive action; Curcumin has the experimental hyperlipidemia rat and falls in blood plasma and the aorta effect that total gallbladder returns pure and mild triglyceride, can promote the metabolism of lipoprotein (a) and reaches blood fat reducing, fat-reducing, antiatherogenic effect; Curcumin has external resisting gram-positive bacteria activity and Salmonella toxicity, even has the activity of certain anti-HIV; Curcumin does not have significantly acute and secular toxic action, even multidrug resistance that can regulate tumor cell, alleviates cytotoxicity.
Matrine (kushenin) is the chemical compound that a class contains matridinde 15 these structures of ketone group, mainly extracts from radix sophorae and Herba Sophorae alopecuroidis, and wherein oxymatrine concentration is more than 98%.Have effects such as antiinflammatory, immunosuppressant, anti-arrhythmia, antiviral and parasiticide.Clinical research result in recent years shows that the topmost pharmacological action of matrine is an anti-hepatitis B virus and to the protective effect of liver.Matrine has stronger inhibitory action to duplicating of hepatitis B virus, and system has dual regulation to premunition, blocks hepatocellular aberrant apoptosis, suppresses the synthetic and significant effect of anti hepatic fibrosis of collagen in the liver.
Summary of the invention
Emodin, premenstruum, research had been found that the activity with stronger resisting coxsackie virus, but also had bigger cytotoxicity, both relevant for cancer cell specific induction of apoptosis, antineoplastic report, suspicious carcinogenesis was arranged again.We select curcumin, matrine and emodin compatibility according to the theory of Chinese medicine compound compatibility attenuation synergistic.Curcumin, matrine all have certain antiviral activity, and the cytotoxicity of matrine is very little simultaneously, and curcumin has the protection cell, lowers Cytotoxic effect, and the two all has antitumor action.The such combination drug of experiment confirm has antivirus action preferably, has also reduced the cytotoxicity and the consumption of emodin simultaneously.
The present invention is achieved through the following technical solutions:
The extracorporeal antivirus effect experiment
1, experiment material
Emodin, curcumin, matrine are provided by this laboratory respectively; The Hep-2 cell is preserved by Wuhan University virus; CVB
3(Nancy strain), HSV-I, HSV-II are preserved by Wuhan University virus.
2, method:
2.1 the toxicity test of medicine pair cell:
Get 96 well culture plates that grow into monolayer Hep-2 cell, discard culture fluid, add the medicine culture fluid of different compositions, variable concentrations, 37 ℃ of 5% CO
2Cultivate 72h, per 12 hours observation of cell forms, and compare with normal cell, mtt assay detects cytoactive.The result shows: the toxicity maximum of emodin pair cell, and matrine pair cell toxicity minimum, after emodin and matrine, curcumin carried out compatibility, cytotoxicity obviously reduced.Its best proportioning is emodin extract 5～50, alkaloid of sophora flavescens ait 5～50, Rhizoma Curcumae Longae total pigment 0～50.
2.2 medicine extracorporeal antivirus effect experiment
According to the replicative cycle of virus, design three medicine antivirus action approach, divide three processed group, according to the result of drug cell toxicity test, determine that with best proportioning 5 medicine final concentrations experimentize between minimal effective concentration and half toxic concentration simultaneously.
1. medicine antiviral absorption group adds the medicine culture fluid of different compositions and concentration in the intact monolayer Hep-2 Tissue Culture Plate of growth, 37 ℃, after 5%CO2 is hatched 1.5h, discard the pastille culture fluid, add viral liquid again, 37 ℃, after 5%CO2 is hatched 1.5h, discard viral liquid, add ordinary cells again and keep liquid continuation cultivation.Through the observation of 72h, typical viral pathological changes, i.e. CPE symptom all appear in each porocyte: the cell growth is disorderly, the cell state distortion, and granule increases, and refractivity increases, and death at last comes off.Illustrate that the breeding of virus in the Hep-2 cell do not suppressed, each organizes medicine does not all have the antiviral adsorption.
2. directly effect group of medicine is formed difference and after the medicine culture fluid of concentration and viral liquid hatches 1.5h with 37 ℃ of volume mixing, add again in the intact monolayer Hep-2 Tissue Culture Plate of growth, 37 ℃, after 5%CO2 is hatched 1.5h, discard pastille and contain virus-culturing fluid, add ordinary cells again and keep liquid continuation cultivation.The result shows that each drug component all has the effect of certain inhibition infection cell pathological changes, and promptly each component all has and directly kills CVB
3Or the effectiveness of HSV virus.
3. medicine antiviral biosynthesis group adds viral liquid in the intact monolayer Hep-2 Tissue Culture Plate of growth, and 37 ℃, after 5%CO2 is hatched 1.5h, discard viral liquid, the medicine of composition of adding difference again and concentration is kept liquid and is continued to cultivate.The result shows that each component all has the effect of certain inhibition infection cell pathological changes, promptly all has the virus of inhibition biosynthetic effectiveness in cell.
Though find out that from above result emodin has certain CVB that directly kills
3, HSV virus and suppress CVB
3, HSV virus is in intracellular biosynthetic effectiveness, but its cytotoxicity is bigger.Though the curcumin cytotoxicity is smaller than emodin, its antiviral efficacy is but not as emodin.The cytotoxicity of matrine is very little, has certain antiviral ability.Through after the compatibility, the cytotoxicity of emodin obviously lowers, and it directly kills CVB
3, HSV virus and suppress CVB
3, the synthetic effect of HSV viral organism also strengthened.
3, anti-CVB in the body
3The virus experiment
3.1 experiment material
According to the extracorporeal antivirus effect experiment, choose the best proportioning of antiviral efficacy and carry out the interior resisting virus experiment; 4 the week age male mice, body weight (18 ± 2) g purchases the Experimental Animal Center in Hubei Province
3.2 experimental technique
1. medicine is to the acute toxicity testing of mice
50 male mices are divided into 5 groups at random, and 10 every group, different pharmaceutical concentration is irritated stomach, 72 hours death condition of record mice, and calculating its LD50 is 850mg/kg.
2. the foundation of animal model
4 age in week 30 of male mices, after the injection site sterilization, lumbar injection CVB
3Virus liquid 0.1ml observes morbidity and the death condition of mice every day, and notes down.Symptoms such as mice appearance activity in 2～4 days reduces, tiredly contract, lose weight, cyanosis begin occurrence law death after 6 days, illustrate that modeling successfully.
3. interior resisting virus experiment
At random 100 mices are divided into 5 groups, every group 20, set up Drug therapy high dose group, middle dosage group, low dose group, positive drug matched group and normal saline matched group respectively, 24h begin treatment behind viral infection sets up the intact animal to contrast 10 simultaneously in addition.Each treats treated animal in CVB
3Put to death 5 after infecting 10d, get blood system from serum behind the excision eyeball, and internal organs such as the animal heart, liver,spleen,kidney are got by the sterile working.Each is organized the mice internal organs and observes down through 10% formaldehyde fixed, paraffin embedding, serial section, HE dyeing, mirror, and record focus number.According to a conventional method, be inoculated in the Hep-2 cell after the aseptic homogenate of mice internal organs, measure virus titer.
Table 1 CVB
3The virus infected mice survival rate relatively
| Group | The treatment number of animals | Survival rate % |
| Dosage group Drug therapy low dose group positive drug matched group normal saline matched group normal control group in the Drug therapy high dose group Drug therapy | 20 20 20 20 20 10 | 70 60 45 5 5 100 |
Table 2 Drug therapy CVB
3Virus titer in the virus infected mice tissue (logTCLD50/0.1ml) relatively
| Group | The heart | Liver | Spleen | Lung | Kidney |
| Dosage group Drug therapy low dose group positive drug matched group normal saline matched group in the Drug therapy high dose group Drug therapy | 22 32 33 54 55 | 22 32 33 54 55 | 22 32 33 44 44 | 22 32 33 44 55 | 22 32 33 44 44 |
This drug regimen of above presentation of results can significantly alleviate the mouse invasion symptom, prolongs its existence natural law, reduces mortality rate; Suppress virus multiplication in the internal organs such as mouse core, liver, spleen, lung, kidney, make infectious virus titre decline, particularly alleviating in these internal organs the myocardial cell pathology damage.This medicine that the present invention determines really is resisting coxsackie virus optimal drug prescription.
4, anti-HSV virus experiment in the body
4.1 experiment material
According to the extracorporeal antivirus effect experiment, choose the best proportioning of antiviral efficacy and carry out the interior resisting virus experiment; The white hair of Dunkin-Harthey Cavia porcellus, body weight 300 ~ 350g, female, purchase Experimental Animal Center in Hubei Province.
4.2 experimental technique
1. animal virus inoculation method
Pentobarbital sodium is anaesthetized Cavia porcellus, back depilation, cleaning, sterile working.At the center of baring skin injecting virus liquid 0.02ml.After the anesthesia, animal is kept in 30 ℃ of environment 2 hours.Observe the skin infection situation.
2. interior resisting virus experiment
At random 20 Cavia porcelluss are divided into 2 groups, 10 every group, be medication therapy groups and matched group, in virus inoculation 24h begin treatment, add the 0.03ml medicine on each self-corresponding dermatotome with micro sample adding appliance, be applied in infection site, till pharmaceutical drying.Smear every day 2 times.Stayed dermatological specimens to do virus titer detected in the 3rd, 5,6,7 day.
Virus titer (logTCLD50/0.1ml) relatively in the table 3 Drug therapy HSV viral infection guinea pig skin
| Group | 3 days | 5 days | 6 days | 7 days |
| Dosage group Drug therapy low dose group positive drug matched group normal saline matched group in the Drug therapy high dose group Drug therapy | 2 3 4 2 4 | 1 2 3 1 6 | 1 2 3 0 6 | 1 1 2 0 6 |
This drug regimen of above presentation of results can significantly alleviate the disease symptom of guinea pig skin, and skin infection sexually transmitted disease (STD) poison titre is descended.This medicine that the present invention determines really is the optimal drug prescription of anti-herpesvirus.
Embodiment 1
1, prescription is selected the pharmaceutical composition and the additives of following consumption for use, the preparation tablet
Emodin 110g
Curcumin 25g
Matrine 95g
Starch 320g
Lactose 25g
Magnesium stearate 5g
2, preparation
Get emodin, curcumin, matrine, starch, lactose mix homogeneously, cross 80 mesh sieves, with 95% ethanol wet granulation, oven dry, granulate adds magnesium stearate, mixing, tabletting, coating, promptly.
Embodiment 2
1, prescription is selected the pharmaceutical composition and the additives of following consumption for use, the preparation dispersible tablet
Emodin 50g
Curcumin 15g
Matrine 35g
Polyethylene glycol 6000 900g
Starch 50g
Magnesium stearate 5g
2, preparation
Get emodin, curcumin, matrine, polyethylene glycol 6000,, get it filled the thing heating for dissolving in an amount of dehydrated alcohol the PEG6000 heating and melting, join again in the carrier under the molten condition and constantly stir, make mix homogeneously, and fling to solvent, pour into rapidly then on the corrosion resistant plate of pre-cooling in 80 ℃ of stirrings, be coated with straticulation, cooling curing under-20 ℃ of conditions, finished product is stored in a few days in the exsiccator, porphyrize, cross 60 mesh sieves, add starch, lactose again, PVP wet granulation, oven dry, granulate, add magnesium stearate, mixing, tabletting, coating, promptly.
Embodiment 3
1, prescription is selected the pharmaceutical composition and the additives of following consumption for use, the preparation ointment
Emodin 45g
Curcumin 10g
Matrine 40g
Glyceryl stearate 80g
Stearic acid 120g
Vaseline 150g
Glycerol 150g
Distilled water 500ml
2, preparation
Get glyceryl stearate, stearic acid, vaseline heating and melting and become liquid phase, glycerol, distilled water are heated to 90 ℃ and are water.Slowly pour water into oil phase, the limit edged stirs, and gets emulsion-type substrate.Emodin, curcumin, matrine are added in the above-mentioned substrate, stir, promptly.
Embodiment 4
1, prescription is selected the pharmaceutical composition and the additives of following consumption for use, the preparation capsule
Emodin 110g
Curcumin 55g
Matrine 100g
Sodium carboxymethyl cellulose 25g
Dextrin 35g
Magnesium stearate 5g
2, preparation
Get emodin, curcumin, matrine, sodium carboxymethyl cellulose, dextrin, magnesium stearate mix homogeneously, cross 80 mesh sieves, dry granulation, granulate, fill is in capsule, promptly.
Embodiment 4
2, prescription is selected the pharmaceutical composition and the additives of following consumption for use, the preparation suspensoid
Emodin 6g
Curcumin 2g
Matrine 5g
Sodium carboxymethyl cellulose 0.2g
Celluloasun Microcrystallisatum 1.0g
Sodium benzoate 0.2g
Distilled water adds to 100ml
2, preparation
Get sodium benzoate and be dissolved in the distilled water, make rubber cement, emodin, curcumin, matrine are added with Celluloasun Microcrystallisatum, sodium carboxymethyl cellulose, mix homogeneously, promptly.
Above example is only for the present invention is further illustrated, and scope of the present invention is not subjected to the limitation that given an actual example.
Claims (5)
1, the compound preparation of a kind of resisting coxsackie virus and herpesvirus, it is characterized in that compound preparation be by emodin, Radix Sophorae Flavescentis biology total alkali, Rhizoma Curcumae Longae total pigment in the formulated medicament of following ratio: emodin 5～50, Radix Sophorae Flavescentis total alkaloids 5～50, Rhizoma Curcumae Longae total pigment 0～50.
2, the compound preparation of resisting coxsackie virus according to claim 1 and herpesvirus is characterized in that it is made up of with one or more Radix Sophorae Flavescentis alkaloid and one or more curcumin prescription emodin or the extract that contains emodin.Radix Sophorae Flavescentis alkaloid comprises matrine, oxymatrine, sophocarpine; The Rhizoma Curcumae Longae total pigment comprises curcumin, demethoxycurcumin and removes the dimethoxy curcumin.
3, the compound preparation of resisting coxsackie virus according to claim 1 and herpesvirus, be equipped with different adjuvants, make the dosage form of corresponding for oral administration or external with different route of administration, be used for the treatment of multiple viral diseases such as myocarditis that Coxsackie virus, herpesvirus cause, herpes zoster.
4, the compound preparation of resisting coxsackie virus according to claim 1 and herpesvirus is characterized in that described dosage form is a said dosage form on any pharmaceutics.
5, the compound preparation of resisting coxsackie virus according to claim 1 and herpesvirus is characterized in that it can being the various dosage forms that are mixed and made into the above adjuvant of any pharmaceutics.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610125582 CN101032482A (en) | 2006-12-26 | 2006-12-26 | Compound preparation resisting coxsackie virus and herpesvirus |
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|---|---|---|---|
| CN 200610125582 CN101032482A (en) | 2006-12-26 | 2006-12-26 | Compound preparation resisting coxsackie virus and herpesvirus |
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| CN101032482A true CN101032482A (en) | 2007-09-12 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102462674A (en) * | 2010-11-04 | 2012-05-23 | 刘丽宏 | Application of curcumin and curcumin derivatives in preparation of drug and/or health care product for treating and preventing diseases related to human cytomegalovirus infection |
| CN102920382A (en) * | 2012-11-22 | 2013-02-13 | 桂林明焕生物科技有限公司 | Cleaner towel capable of preventing hand-foot-mouth disease and preparation method of cleaner towel |
| CN103127471A (en) * | 2013-03-22 | 2013-06-05 | 牛德兴 | Traditional Chinese medicine for treating recurrent genital herpes |
| CN104288146A (en) * | 2014-10-28 | 2015-01-21 | 江滟 | Application of oxymatrine in preparing drugs treating Coxsackie virus infectious diseases |
-
2006
- 2006-12-26 CN CN 200610125582 patent/CN101032482A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102462674A (en) * | 2010-11-04 | 2012-05-23 | 刘丽宏 | Application of curcumin and curcumin derivatives in preparation of drug and/or health care product for treating and preventing diseases related to human cytomegalovirus infection |
| CN102462674B (en) * | 2010-11-04 | 2014-04-02 | 刘丽宏 | Application of curcumin and curcumin derivatives in preparation of drug and/or health care product for treating and preventing diseases related to human cytomegalovirus infection |
| CN102920382A (en) * | 2012-11-22 | 2013-02-13 | 桂林明焕生物科技有限公司 | Cleaner towel capable of preventing hand-foot-mouth disease and preparation method of cleaner towel |
| CN103127471A (en) * | 2013-03-22 | 2013-06-05 | 牛德兴 | Traditional Chinese medicine for treating recurrent genital herpes |
| CN103127471B (en) * | 2013-03-22 | 2014-03-26 | 牛德兴 | Traditional Chinese medicine for treating recurrent genital herpes |
| CN104288146A (en) * | 2014-10-28 | 2015-01-21 | 江滟 | Application of oxymatrine in preparing drugs treating Coxsackie virus infectious diseases |
| CN104288146B (en) * | 2014-10-28 | 2017-08-01 | 江滟 | Oxymatrine is preparing the application for the treatment of Coxsackie virus infection disease medicine |
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Open date: 20070912 |