CN1279107A - Medicine for treating AIDS and tumor and its preparing process - Google Patents
Medicine for treating AIDS and tumor and its preparing process Download PDFInfo
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Abstract
A medicine for treating AIDS and cancers is prepared from castor, phytolacca root, liquorice root and pine cone through extracing phytolaccatoxin, phytolaccapolyose, ricin, glycyrrhizic acid for injection and pineal acidic polyose and preparing them into injection and slow-releasing capsules. Its advantages include high killing power to HIV and cancer cells, high curative effect, and no toxic by-effect.
Description
The present invention relates to a kind of medicament for the treatment of acquired immune deficiency syndrome (AIDS) and tumor and preparation method thereof.
At present, treatment acquired immune deficiency syndrome (AIDS) and tumor are difficult problems that needs to be resolved hurrily medically, though there are a lot of physicians to do a lot of valuable must work for this reason,, also do not have the medicine of a kind of effectively treatment of AIDS and tumor.
Purpose of the present invention will solve this difficult medical problem exactly, provides a kind of remarkably productive, safe in utilization, and prescription is unique, the reparation technology section medicament of treatment acquired immune deficiency syndrome (AIDS) and tumor and preparation method thereof that learns.
For achieving the above object, the present invention is by the following technical solutions:
A kind of medicament for the treatment of acquired immune deficiency syndrome (AIDS) and tumor is characterized in that its prescription is made up of Semen Ricini, Radix Phytolaccae, Radix Glycyrrhizae, strobile.
A kind of medicaments preparation method for the treatment of acquired immune deficiency syndrome (AIDS) and tumor is characterized in that processing step is as follows:
(1), ricin extraction process: peel off the outer duricrust of Semen Ricini earlier, white core pestle is become pasty state, remove Oleum Ricini
(1) centrifugal after 3 times of amounts of adding below 12 ℃ ethanol soak 4 hours, get its precipitation, pinch moltenly with water, the aqueous solution lyophilization promptly gets semifinished product, semifinished product aqueous solution filtering insoluble matter, add an amount of ethanol, place a moment, the filtering precipitation, mother solution adds small amount of ethanol again to little apparent muddiness, put and separate out crystallization in the refrigerator, in case of necessity recrystallization again;
(2), ethanol precipitation classification: Semen Ricini is stuck with paste and adds 3 times of amount ethanol, has precipitation to separate out centrifugal removing; Add 1 times of amount ethanol in this mother solution again, this partly precipitated of centrifugal collection, but still impure, add 1 times of amount ethanol in this mother solution again, the protein of then separating out is purer, and precipitation is used water dissolution, and lyophilization gets product;
(3), injection lactobionic acid ricin is dry and cold freezes crystalline producing: require aforementioned lipidated protein to reach 99.9% when above, with water dissolution, method purification secondary with DEAE-cellulose chromatography promptly gets pure product crystallization, adds galactobionic acid Galactonic acid vacuum lyophilization promptly; The pure product ricin of gained, must 100% do not contain Semen Ricini because of and ricidine.;
(2), (1). the phytolaccatoxin extraction process:
Radix Phytolaccae thin slice extracting in water three times adds 8 times of amounts for the first time, boils filtration in 4 hours, second and third time adds 4 times of water gagings, boils 2 hours, and filtration, filtrate merge, concentrate the quintuple of ending medicine, get concentrated sulphuric acid and slowly be added in the concentrated solution, the limit edged stirs, concentrated solution 1000ml adds sulphuric acid 40g, after adding, boil to little and boiled 4 hours, put cold, pour in the equivalent cold water, stir evenly, placement is spent the night, abandoning supernatant, residual liquid is a sedimentation and filtration, precipitation wash with water to pH value be about 6, filter collection precipitation is drained, to dry below 60 ℃, the crude product phytolaccanine had both been got;
(2). the Radix Phytolaccae polysaccharide extracting process:
The Radix Phytolaccae sheet adds 5 times of amounts of 75% ethanol 0.5NNaoH, and reflux 2 hours is extracted three times with method; Merging filtrate is condensed into cream, adds 95% ethanol and is stirred to precipitation then, spends the night, and filters, and reclaims ethanol, continuous 2 times; Add 2 times of amounts of water, with DEAE cellulose chromatography purification, column chromatography purification is 2 times continuously, gets pure Radix Phytolaccae polysaccharide PEP-1;
(3), injection glycyrrhizic acid extraction process:
Radix Glycyrrhizae powder is concentrated into original volume 1/5 filtration with 12 times of amount 0.5% ammonia seepages, effusion, and filtrate adds concentrated sulphuric acid to PH3, filters the precipitation of separating out, and washes 3 times, and is dry below 60 ℃, gets thick glycyrrhizic acid
Pure product glycyrrhizic acid extracts: with the thick glycyrrhizic acid 400g of aforementioned gained, add 4 times of amount industrial alcohol, reflux three hours, filter, filtrate adds 2 times of amount alcohol refluxs 2 times, merges backflow and adds the 10g active carbon, reflux decolour cooling half an hour, filtration, the logical ammonia of filtrate is to PH7-7.5, till no solid is separated out; Filter collection precipitation, with the small amount of ethanol washing, drying at room temperature gets ammonium glycyrrhizinate 250g, continues 80% ethanol with 4 times of amounts, and heating for dissolving is also used activated carbon decolorizing, cold filtration, filtrate concentrates, and separates out white crystals, is pure glycyrrhizic acid.
(4), the strobile acidic polysaccharose is purified:
(1), strobile cleans and to dry, and pulverizes coarse powder, 500g adds 0.5NNaoH solution 4000ml, soaks half an hour, decocts 1 hour, with 4 layers of filtered through gauze, the not good liquor of winning;
(2), medicinal residues are added 0.5NNaoH distilled water 3000ml, decocted 40 minutes, 4 layers of filtered through gauze, second not good liquor;
(3), medicinal residues add 0.5NNaoH distilled water solution 2000ml, decocted 40 minutes, 4 layers of filtered through gauze, liquid for the third time;
(4), the merging of aforementioned three times filtrate be condensed into syrupy shape, place, add 95% ethanol, with adding with being stirred to precipitation fully, placement is spent the night, and reclaims ethanol, and gained liquid is placed 4 hours after-filtration again, filtrate shortens cream into;
(5), extract is acidic polysaccharose, if make used for intravenous injection, again with water dissolution, with the DEAE cellulose chromatography secondarily purified both pure product;
(5), injection preparation process:
(1) the dry and cold crystalline substance that freezes of lactobionic acid ricin, refining every of the pure product of ricin contain 20mg and add the vacuum lyophilization of equivalent 0.1M galactose in addition promptly;
(2), the injection preparation of treatment acquired immune deficiency syndrome (AIDS) and tumor: every bottle contains Radix Phytolaccae acidic polysaccharose 500mg, strobile acidic polysaccharose 2000mg, glycyrrhizic acid 2500mg adds to 100ml with water for injection, sterilization both;
(6), slow releasing capsule is produced: the pure product people of ricin consumption 1ml/kg/ day, the pure product of phytolaccatoxin, 1mg/kg/ day, Radix Phytolaccae polysaccharide 10mg/kg/ day, the pure product of phytolaccotoxin albumen, 1mg/kg/ day, strobile acidic polysaccharose 40mg/kg/ day, Radix Glycyrrhizae albumen 50mg/kg/ day; Calculate to extract 6 kinds of compositions by people 50kg body weight, everyone is ricin 50mg/50kg/ day day by day, phytolaccatoxin 50mg/50kg/ day, Radix Phytolaccae polysaccharide 500mg/50kg/ day, phytolaccotoxin albumen 50mg/50kg/ day, strobile acidic polysaccharose 2000mg/50kg/ day, glycyrrhizic acid 2500mg/50kg/ day, add up to 5150mg altogether, divide 12 No. 1 capsule dresses, each capsule dress 429mg.
The medicaments preparation method of aforementioned therapies acquired immune deficiency syndrome (AIDS) and tumor, wherein the 2nd step can also be the salt classification sedimentation method in the ricin extraction process: former pastel adds the degree of saturation of ammonium sulfate to 40%, so the precipitation color is darker, centrifugal removing; Mother solution adds the degree of saturation of ammonium sulfate to 50%, collects this partly precipitated, but impure; Mother solution adds ammonium sulfate to 75% saturation again, and the gained protein precipitation is purer.
The medicaments preparation method of aforementioned therapies acquired immune deficiency syndrome (AIDS) and tumor, wherein the also available Radix Glycyrrhizae extractum of the extraction of thick glycyrrhizic acid extracts in the injection glycyrrhizic acid extraction process, and method is as follows:
Radix Glycyrrhizae extractum 3kg, heating for dissolving is chilled to room temperature in 36 premium on currency, cross the stirring limit and drip the 145ml concentrated sulphuric acid; Leave standstill a few hours after adding, filter collection precipitation, the water thorough washing in oven dry below 60 ℃, gets thick glycyrrhizic acid 1.2kg, and content is about 55%.
Effect of the present invention is as follows:
1, this medicine innovation reasonable recipe: by ricin, Radix Phytolaccae polysaccharide, strobile acidic polysaccharose, ammonium glycyrrhizinate, never see that from various literature searches ricin is used for the clinical report of controlling human cancer and acquired immune deficiency syndrome (AIDS), and clinical obvious effective rate, the effective percentage controlled is very high, and toxic and side effects is very little.
2, all extract drugs technology advanced persons of this side: the purity height, institute's toxic side effect is minimum, special ricin except that ethanol extracts repeatedly, and with twice grading purification dna purity of DEAE cellulose chromatography more than 99.9%.Again through 2 repeated examinations, 100% do not contain Semen Ricini because of and ricidine..Owing to combine with the carbohydrate receptor of cell surface with discharging the B marriage chain after 0.1M galactose obstruction ricin S-S chain cracking, to irrelevant cancerous cell unrestraint and lethal effect.
In addition: though phytolaccatoxin has very strong inhibition tumor promotion, hemolytic reaction is arranged, thus only make capsule oral, not as the injection input.But the phytolaccagenic acid polyoses extract has anti-tumor activity, makes the injection infusion.The acidic polysaccharose that extracts all extract repeatedly and with twice grading purification of DEAE cellulose (phosphate type) column chromatography, purity reaches more than 99.9%, so side effect is minimum through ethanol.
3, new Chinese medicine purification reasonable combination: lactobionic acid Semen Ricini fibroin dry freeze crystallization: lose activity because ricin is met heat, so extract at low temperature, dry freeze crystallization is pacified bottled, airtight cryopreservation.With discharging B chain and the combination of cell surface carbohydrate receptor after galactose obstruction ricin S-S chain cracking.To human normal cell line, unrestraint and lethal effect.Radix Phytolaccae acidic polysaccharose, strobile acidic polysaccharose, three kinds of polysaccharide extracts of ammonium glycyrrhizinate all have very powerful antitumor and anti-AIDS activity, anti-HIV-1 reverse transcription and translation.Three kinds of polysaccharides and do not have incompatibility, thus three kinds of polysaccharide with adorning a liquid bottle, efficacy stability has synergism.With the crystallization of lactobionic acid ricin dry freeze, behind water dissolution, shake up the back infusion in the adding Chinese mugwort tumor health injection before the injection.Medicine make glycyrrhizic acid can stop ricin thermal source and anaphylaxis, but antitumor and anti-HIV-1 virus function is stronger with advancing in the body like this.But before the crystallization of injection lactobionic acid ricin dry freeze, also need make skin test, positive person does not use.This simple treatment acquired immune deficiency syndrome (AIDS) and the injection of tumor also can be imported in the body.
4, strong inhibition killing tumor cell effect, controlling aspect the carcinoma, ricin, strobile acidic polysaccharose, ammonium glycyrrhizinate, Radix Phytolaccae acidic polysaccharose, the protein synthesis that very strong anti-tumor activity anticancer is all arranged, the ribonucleic acid elongation factor reduces, the DNA (deoxyribonucleic acid) inactivation suppresses and the killing tumor cells target cell.Have than strong selectivity lethal effect, particularly ricin when galactose exists 10
-9-10
-10M, immunotoxin (79:Ricin) can kill 99.9%Nalm-1 target cell.Kaposi there is strong lethal effect, but the human normal cell is not had obvious inhibition and lethal effect.
5, very strong anti-HIV effect: aspect treatment acquired immune deficiency syndrome (AIDS) (HIV-1): strobile acidic polysaccharose, ammonium glycyrrhizinate, Radix Phytolaccae acidic polysaccharose, ricin all have and very strong kill and wound and suppress HIV-1 and duplicate, breed.Particularly strobile extracts polysaccharide, PC
6Can suppress the proteic expression of HIV in the cem cell-1, PC
6Can suppress HIV-1 transcribing and translating in cem cell.PC
6Inducing HIV-1 inhibitive factor is a kind of new immunologic active material.Glycyrrhizic acid suppresses and kills and wounds the HIV cell, and 0.5mg/ml can make 98%HIV-1 propagation be suppressed.
6, our forceful drug effect, immune system there is very strong regulating action: cellular immunization and humoral immunization inhibitory action and immunological enhancement are arranged, both sides' regulating action, can induce r-interference element (interleukin II (IL-2) of IFN-r), interleukin-3 (IL-3), the a tumor necrosis factor (TNF-a), B-transforming factor (TBF-B1), HTV-1 inhibitive factor, natural killer cell (NK cell), these immunologic active materials are to regulating immunity, suppress carcinoma, suppressing HTV has remarkable effect.
7, antibiotic, antifungal, inhibition virus function: can suppress golden Portugal bacterium, streptococcus, fungus and virus function, especially carcinoma be merged antibacterial, virus, infection and HIV-1 and merge each bacterioid, fungus, sick plain the infection very strong inhibition lethal effect is arranged.HTV-1 pneumocystis carinii pneumonia has strong therapeutical effect.
8, our medicine has very strong solution toxic action, anti-allergic effects: can remove the toxin that various carcinoma produce, extracellular toxin that bacterial infection causes and interior plain toxin, HIV-1 pneumocystis carinii pneumonia have strong therapeutical effect.In addition: glycyrrhizic acid can be removed ricin to the human body toxic and side effects, and anti-allergic effects is arranged.
9, the innovation of administration of TCD: four kinds of capsules that medicine is formed, calculate dose day by day by the 50kg body weight, day once or part vic, owing to press cancerous cell and HTV growing multiplication cycle, so took medicine in 2-3 days 1 day, or venoclysis in 2-3 days a day, medication had both reduced toxic reaction like this, make 1-2 days intermissions normal cell recover active again, breed, secrete IFN-r, IL-2, NK, TNF-a etc., strengthened immunologic function again.
10, this medicine medicine source is wide, cheap, and the curative effect height, toxic and side effects is little, and is easy to utilize.
The invention will be further described below in conjunction with embodiment.
Embodiment one:
Get Semen Ricini, Radix Phytolaccae, Radix Glycyrrhizae, strobile ready and produce the medicament of treatment acquired immune deficiency syndrome (AIDS) and tumor by following processing step:
(1), ricin extraction process: peel off the outer duricrust of Semen Ricini earlier, white core pestle is become pasty state, remove Oleum Ricini
(1), centrifugal after 3 times of amounts of adding below 12 ℃ ethanol soak 4 hours, get its precipitation, pinch moltenly with water, the aqueous solution lyophilization promptly gets semifinished product, semifinished product aqueous solution filtering insoluble matter, add an amount of ethanol, place a moment, the filtering precipitation, mother solution adds small amount of ethanol again to little apparent muddiness, put and separate out crystallization in the refrigerator, in case of necessity recrystallization again;
(2), ethanol precipitation classification: Semen Ricini is stuck with paste and adds 3 times of amount ethanol, has precipitation to separate out centrifugal removing; Add 1 times of amount ethanol in this mother solution again, this partly precipitated of centrifugal collection, but still impure, add 1 times of amount ethanol in this mother solution again, the protein of then separating out is purer, and precipitation is used water dissolution, and lyophilization gets product;
(3), injection lactobionic acid ricin is dry and cold freezes crystalline producing: require aforementioned lipidated protein to reach 99.9% when above, with water dissolution, method purification secondary with DEAE-cellulose chromatography promptly gets pure product crystallization, adds the vacuum lyophilization of 0.1M galactobionic acid Galactonic acid promptly; The pure product ricin of gained, must 100% do not contain Semen Ricini because of and ricidine.;
(2), (1). the phytolaccatoxin extraction process:
Radix Phytolaccae thin slice extracting in water three times adds 8 times of amounts for the first time, boils filtration in 4 hours, second and third time adds 4 times of water gagings, boils 2 hours, and filtration, filtrate merge, concentrate the quintuple of ending medicine, get concentrated sulphuric acid and slowly be added in the concentrated solution, the limit edged stirs, concentrated solution 1000ml adds sulphuric acid 40g, after adding, boil to little and boiled 4 hours, put cold, pour in the equivalent cold water, stir evenly, placement is spent the night, abandoning supernatant, residual liquid is a sedimentation and filtration, precipitation wash with water to pH value be about 6, filter collection precipitation is drained, to dry below 60 ℃, the crude product phytolaccanine had both been got;
(2). the Radix Phytolaccae polysaccharide extracting process:
The Radix Phytolaccae sheet adds 5 times of amounts of 75% ethanol 0.5NNaoH, and reflux 2 hours is extracted three times with method; Merging filtrate is condensed into cream, adds 95% ethanol and is stirred to precipitation then, spends the night, and filters, and reclaims ethanol, continuous 2 times; Add 2 times of amounts of water, with DEAEN cellulose chromatography purification, column chromatography purification is 2 times continuously, gets pure Radix Phytolaccae polysaccharide PEP-1;
(3), injection glycyrrhizic acid extraction process:
Radix Glycyrrhizae powder is measured 0.5% ammonia seepages with 12 times, effusion is concentrated into original volume 1/5 and filters, filtrate adds concentrated sulphuric acid to PH3, the precipitation that filtration is separated out, wash 3 times, dry below 60 ℃, getting the pure product glycyrrhizic acid of thick glycyrrhizic acid extracts: with the thick glycyrrhizic acid 400g of aforementioned gained, add 4 times of amount industrial alcohol, reflux three hours, filter, filtrate adds 2 times of amount alcohol refluxs 2 times, merges backflow and adds the 10g active carbon, reflux decolour cooling half an hour, filtration, the logical ammonia of filtrate is to PH7-7.5, till no solid is separated out; Filter collection precipitation, with the small amount of ethanol washing, drying at room temperature gets ammonium glycyrrhizinate 250g, continues 80% ethanol with 4 times of amounts, and heating for dissolving is also used activated carbon decolorizing, cold filtration, filtrate concentrates, and separates out white crystals, is pure glycyrrhizic acid.
(4), the strobile acidic polysaccharose is purified:
(1), strobile cleans and to dry, and pulverizes coarse powder, 500g adds 0.5NNaoH solution 4000ml, soaks half an hour, decocts 1 hour, with 4 layers of filtered through gauze, the not good liquor of winning;
(2), medicinal residues are added 0.5NNaoH distilled water 3000ml, decocted 40 minutes, 4 layers of filtered through gauze, second not good liquor;
(3), medicinal residues add 0.5NNaoH distilled water solution 2000ml, decocted 40 minutes, 4 layers of filtered through gauze, liquid for the third time;
(4), the merging of aforementioned three times filtrate be condensed into syrupy shape, place, add 95% ethanol, with adding with being stirred to precipitation fully, placement is spent the night, and reclaims ethanol, and gained liquid is placed 4 hours after-filtration again, filtrate shortens cream into;
(5), extract is acidic polysaccharose, if make used for intravenous injection, again with water dissolution, with the DEAE cellulose chromatography secondarily purified both pure product;
(5), injection preparation process:
(1), the dry and cold crystalline substance that freezes of lactobionic acid ricin, refining every of the pure product of ricin contain 20mg and add the vacuum lyophilization of equivalent 0.1M galactose in addition promptly;
(2), the injection preparation of treatment acquired immune deficiency syndrome (AIDS) and tumor: every bottle contains Radix Phytolaccae acidic polysaccharose 500mg, strobile acidic polysaccharose 2000mg, glycyrrhizic acid 2500mg adds to 100ml with water for injection, sterilization both;
(3), freeze brilliant 20-60mg with aforementioned lactobionic acid ricin is dry and cold, add injection water 2-6ml, or amount adds in the injection of treatment acquired immune deficiency syndrome (AIDS) and tumor on demand;
(6), slow releasing capsule is produced: the pure product people of ricin consumption 1ml/kg/ day, the pure product of phytolaccatoxin, 1mg/kg/ day, Radix Phytolaccae polysaccharide 10mg/kg/ day, the pure product of phytolaccotoxin albumen, 1mg/kg/ day, strobile acidic polysaccharose 40mg/kg/ day, Radix Glycyrrhizae albumen 50mg/kg/ day; Calculate to extract 6 kinds of compositions by people 50kg body weight, everyone is ricin 50mg/50kg/ day day by day, phytolaccatoxin 50mg/50kg/ day, Radix Phytolaccae polysaccharide 500mg/50kg/ day, phytolaccotoxin albumen 50mg/50kg/ day, strobile acidic polysaccharose 2000mg/50kg/ day, glycyrrhizic acid 2500mg/50kg/ day, add up to 5150mg altogether, divide 12 No. 1 capsule dresses, each capsule dress 429mg.
Embodiment two:
Other step is identical, and difference place is:
The 2nd step is the salt classification sedimentation method in the aforementioned ricin extraction process: former pastel adds the degree of saturation of ammonium sulfate to 40%, so the precipitation color is darker, and centrifugal removing; Mother solution adds the degree of saturation of ammonium sulfate to 50%, collects this partly precipitated, but impure; Mother solution adds ammonium sulfate to 75% saturation again, and the gained protein precipitation is purer.
The extraction of thick glycyrrhizic acid is extracted with Radix Glycyrrhizae extractum in the aforementioned injection glycyrrhizic acid extraction process, and method is as follows:
Radix Glycyrrhizae extractum 3kg, heating for dissolving is chilled to room temperature in 36 premium on currency, cross the stirring limit and drip the 145ml concentrated sulphuric acid; Leave standstill a few hours after adding, filter collection precipitation, the water thorough washing in oven dry below 60 ℃, gets thick glycyrrhizic acid 1.2kg, and content is about 55%.
The treatment acquired immune deficiency syndrome (AIDS) of producing by previous embodiment and the medicament of tumor, its pharmacology, prison bed are used, plain side effect is as follows:
One, this prescription pharmacological action:
1, antitumor action: can suppress the synthetic of tumor, oncoprotein, it is synthetic to suppress the tumor target cell, there is earlier selecting property kill and wound to cancerous cell with using, to leukemia, cervical cancer U14, sarcoma S180, ehrlich carcinoma, ascites hepatocarcinoma, lung cancer cell line HIV-1 cause that kaposi's sarcoma (Kaposi) all has inhibition and lethal effect.
2, anti AIDS virus (HIV-1) effect: this medicine is to the propagation of HIV-1 and duplicated very strong inhibitory action, can suppress the expression of cem cell HIV-1, can suppress HIV-1 transcribing and translating in cem cell again, gene expression also has very strong inhibitory action to LTR guiding DNA at transcriptional level.
3, to the immune system effect:
(1) anti-allergic effects: glycyrrhizic acid can suppress that ricin causes allergic reaction and to the infringement of liver, spleen, the heart, kidney.
(2) immunity there is dual regulation.
(3) very strong immunosuppressive action is arranged.
(4) strengthen and induce lymphocyte branch interleukin-2 (IL-2) and the r-interference element (IFN-r) that oozes.Promote splenocyte DNA and protein synthesis and splenocyte to produce IFN-r.
(5) can induce the macrophage activating factor (MAF) (interleukin-3 (IL-3) of GM-CSF).B-transforming factor (TGF-B1), a-tumor necrosis factor (TNF-a).
Two, single pharmacological action:
(1) 1. Radix Phytolaccae influences immune system:
(1) stimulate the lymphocyte transformation effect: 1. Radix Phytolaccae mitosis proper energy promotes lymph T cell and B cell transformation, division, propagation.2. Radix Phytolaccae glycoprotein (PWM), T and B cell be in the presence of macrophage, and PHA and PWM are responded produces interferon (IFN).3. Radix Phytolaccae polysaccharide-1 or Radix Phytolaccae polysaccharide-2 (PEP-1) can transform propagation by induction of lymphocyte.
(2) inducement interferon effect: 1. Radix Phytolaccae has a branch source, and concanavalin A can induce leukocyte to produce interferon (IFN).2. Radix Phytolaccae glycoprotein (PWM), T and B cell can both react generation interference element (IFN) to PHA and PWM in the presence of macrophage.3. phytolaccatoxin (ES) is to splenocyte born of the same parents inducement interferon-r (IFN-r).4. Radix Phytolaccae polysaccharide I (PEP-I) can induce macrophage and produce interleukin I (IT-I).Splenocyte be can induce and interleukin II (IL-2), PEP-I or II stimulation splenocyte generation colony stimulating factor (CSF) (CSF is IL-3) produced.
(3) the liver spleen is organized mixed influence in the 3H thymidine body: phytolaccatoxin (SE) is a kind of biological activity material of activated oligonucleotide reductase, and PWM also can stimulate the vigor of B cell to born of the same parents' gland nucleoside.Thereby the metabolism of promotion DNA.Strengthen cellular immune function.
2, antitumor action:
(1) phytolaccatoxin induces r-interferon (IFN-r) interleukin-2 and lymphotoxin (IT).Contain these lymphokine goods, to human lung carcinoma cell line (SPC-3).Human T lymphocyte's leukemia cell line (Jurkat and Moit-4 cells), human cervical carcinoma cell strain (Hela cell), human hepatoma cell strain (SMMC-7721) etc. all has cytotoxicity.To human normal cell line (WISH) free of toxic effects.
(2) phytolaccatoxin suffering (EH) and lipopolysaccharide (IPS) can secreting tumor necrosis factor (TNF) be a kind of cytokines of killing tumor cell.
(3) Radix Phytolaccae polysaccharide (PEP-1) activating macrophage (M φ) and startup production of TNF induced are its antitumor actions, inhibitory rate 51.7%.Suppress tumor growth by strengthening the T cell function.
3, antiinflammatory, antibiotic, antiviral:
(1) 1. pokeweed antiviral protein (PAP) can significantly improve and strengthen the IgG effect.2. phytolaccatoxin has obvious inhibitory action to multiple active chronic inflammation, and can reduce capillary permeability.3. it is similar to hydrocortisone that Radix Phytolaccae extracts triterpenic acid antiinflammation intensity.4. Saponin E and jaligonic acid have tangible antiinflammatory action.
(2) antivirus action: contained antiviral protein of Radix Phytolaccae (PAP) and glycoprotein (PWM) have stronger antiviral activity to HIV (human immunodeficiency virus), poliomyelitis III type virus, anti-tabacco mosaic poison.
4, Radix Phytolaccae has analgesic, analgesia, myorelaxant effects.
5, Radix Phytolaccae pharmacokinetic: 4 days lumbar injection Radix Phytolaccaes of mice polysaccharide I, the peak time that induces tumor necrosis factor (TNF) is the 8th day behind the biphasic injection, the hot inductive TNF of phytolaccatoxin secretes in time Yan Chang and increases gradually, reaches the peak in about 24 hours.
6, phytolaccotoxin side effect:
The acid steroid saponin that pokeroot extracts, mouse peritoneal injection LD50 is 65mg/kg.In continuous 3 weeks of decoct mouse stomach 5g/kg every day, the weight of animals and state do not have significant change, and behind the sacrifice of animal, year does not obviously change for the heart, liver, lung, kidney.
(2) the contained ricin of Semen Ricini (Ricin):
(1), antitumor action: but the protein synthesis of the various cancerous cell of ricin strong inhibition, it is synthetic that moderate strength suppresses DNA, and slight to the synthetic inhibitory action of RNA, but the ribosomal protein synthesis of strong inhibition eukaryote.Have when connecting into immunotoxin ricin-737 ricin and connect into the external 0.1M lactose of immunotoxin ricin-737 (ricin-737) and exist by disulfide bond by disulfide bond at reactive Mab-737 ricin of B cell class 1a antigen-specific, this antibody element (IT) shows optionally brute force to the Burkitt lymphomas cell line Rajj cell that contains B cell antigen and kills and wounds, and does not contain the no lethal effect of target antigen.Immunotoxin 1h just can suppress target cell propagation, and prolongation in time kills and wounds more remarkable.The tumor target cell is shown selective killing effect, to target cell protein synthesis suppression ratio 71%.Ricin is to the mice ehrlich carcinoma, ascites hepatocarcinoma, and cervical cancer U14, meat slip S180, and transplanted tumors such as leukemia all have certain therapeutical effect; In inoculation back 1,3b lumbar injection 7.5mg/kg can suppress Emhorn abdominal cavity water growth of cancer cells fully; Chamber, 1 abdominal cavity injection 25mg/kg, can make cancerous cell minimizing nearly all cancerous cell form change after 90%, 96 hour after 48 hours: nucleus expands, and cavity appears in core, and mitosis stops, and endochylema secretly dyes, and occurs irregular cavity etc. on every side.
Ricin has two peptide chains, is made up of S-S chain, and a cracking process is arranged before having an effect, and discharges the A chain after the cracking---and effect chain, B chain are marriage chain; A chain or whole toxalbumin molecule enter endochylema by plasma membrane, have an effect with nucleoprotein 60-S subunit, suppressing aminoacyl t-RNA combines with ribosomal acyl, the elongation factor of nucleic acid is reduced, the nucleic acid inactivation, Profilin matter is synthetic, causes cell death, and the B chain can combine with the carbohydrate of cell surface; After the B chain seals the cell binding site of its B chain with the 0.1M galactose, has the strong target cell killing activity of high special.
Immunotoxin (IT) is a comparatively ideal class tumor targeted therapy medicine: Semen Ricini fibroin and amycin are coupled to and have made up first on the antihuman bladder cancer monoclonal antibody molecule and have the antineoplastic guide medicine of two bullets, in the presence of the 0.1mol/L galactose, irrelevant cancerous cell there is not lethal effect, stronger 10 times to killing and wounding of human bladder cancer BIU-87 and E-J cell than McSb-Ricin with using, stronger 30,000 times than McAb-Abuiamycin.Has the strong killing tumor cells target cell of high special activity.
(2), to Immune Function: humoral immunization and cellular immunization are had very strong inhibitory action.
(3), sensitization: ricin has severe allergic reaction, its incidence rate 85.11%.
(4), toxic and side effects: the contained Semen Ricini of Semen Ricini both can make the adult dead because of (ricin) 7mg or ricidine. (ticinine) 0.16g.These two kinds of composition heating were both destroyed.But through column chromatography repeatedly purification obtain pure product ricin more than 99.9%, do not have this toxic ingredient.
Acute subacute toxicity effect:
Ricin is 6-12mg to 1 quiet notes LD50 of mice, but the LD50 report to mice is different, the more above-mentioned LD50 of most reports is big, be due to the sample purity difference, ricin various kinds, product through DEAE cellulose grading purification, LK50 to the once malicious arteries and veins injection of rat is 50-150mg/kg, other report ricin to mice once the LD50 of quiet notes be 47.97mg/kg, to rabbit once the MTK of quiet notes be 3.2mg/kg, continuous once a day 16 times MTD is 1.6mg/kg to the quiet notes of rabbit.
Ricin has severe toxicity to mice, and is also influential to hereditary material.
(3) the contained glycyrrhizic acid of Radix Glycyrrhizae (glycyrrhizin) glycyrrhizin, licoflavone.
1, immune system is influenced:
(1) antianaphylaxis effect: complex that Radix Glycyrrhizae is extracted (LX) contains protein, nucleic acid, polysaccharide, glycyrrhizic acid anti-allergic effects preferably, and the mouse allelgic shock is also had protective effect, to anaphylactic shock and dead suppression ratio more than 95%.Glycyrrhizic acid 25～50mg/kg can significantly suppress anaphylaxis, can stop sensitive media to discharge.
(2) non-specific immunity is influenced: 1. glycyrrhizin can strengthen the reticuloendothelial system activity, makes total white blood cells increase neutrophil, and the mononuclear cell increase is more obvious, and the effect of the macrophage phagocytic of stimulation is arranged.2. reticuloendothelial system and natural killer cell activity there is remarkable enhancing.
(3) influence of antagonist generation: 1. glycyrrhizic acid can make antibody significantly increase, and 30mg/kg can make antibody produce significantly enhancing.2. antagonist produces inhibitory action, and it is that T is cell-mediated that Radix Glycyrrhizae suppresses 1gE synthetic, and relevant with the CD8+ cell.3. the Radix Glycyrrhizae antagonist produces two-way function: i.e. reaction to normal source of disease has potentiation, and the anaphylaxis of abnormality then is inhibitory action.
(4) complement is influenced: the glycyrrhizic acid intramuscular injection all can suppress 50% haemolysis to CP50 and AP50, can suppress complementary reaction, and the related inflammation process is alleviated and be static.
(5) to the generation and the inducement interferon effect of interleukin-2: glycyrrhizic acid 100ug/ml obviously promotes activatory splenocyte DNA of concanavalin A, Con A (ConA) and proteinic biosynthesis, the synthetic peak of DNA 48 hours.(IL-2) produces obvious potentiation to interleukin II, and glycyrrhizic acid can strengthen ConA induction of lymphocyte secretion IL-2.And (IFN-r), it is main can improving splenocyte generation IFN-r can to strengthen ConA induction of lymphocyte secretion r-interferon.
(6) to prostaglandin: prostate is have dual regulation.
(7) natural killer cell (NK) activity there is remarkable potentiation, immunity of organism is had important regulating action.
2. the effect of anti AIDS virus (HIV)
(1) glycyrrhizin 0.5mg/ml suppresses more than 98% the propagation of HIV, and 50% plaque forms inhibiting value 0.125mg/ml, but can not suppress the reverse transcription of HIV, is to play a role by recovering the T cell.
(2) glycyrrhizin presses down HIV proliferation inhibition rate 78.81%, can destroy the HIV cell.
(3) glycyrrhizic acid 0.5mg/ml can make 98%HIV propagation be suppressed, and 0.125mg/ml solution can make 50%HIV propagation be suppressed.
(4) the anti-HIV effect of licoflavone class: fabulous anti-HIV effect is arranged, and 3 kinds of flavone compositions are arranged in the Radix Glycyrrhizae, and effect is 25 times of glycyrrhizin to the HIV inhibition of proliferation.
(5) Angelica Polysaccharide has anti-vesicular stomatitis virus, adenovirus, vaccinia virus, herpes simplex virus.
3. antibacterial action: glycyrrhizic acid and subacid all have inhibitory action to golden Portugal bacterium, tubercule bacillus, escherichia coli, ameba, infusorian, and 6.25-12.5ug/ml is bacteria growing inhibiting fully.
4. antitumor, antitumaous effect:
(1) glycyrrhizic acid is to rat ascites hepatocarcinoma and ehrlich carcinoma, and yoshida sarcoma all has inhibitory action.
(2) enoxolone has inhibitory action to myeloma, ascites hepatocarcinoma, leukemia.
(3) glycyrrhizin have hepatocarcinoma due to the obvious inhibition flavacin, yoshida sarcoma, ascites hepatocarcinoma, ehrlich carcinoma.
(4) glycyrrhizin all has inhibitory action to mouse ascites fluid hepatocarcinoma, ehrlich carcinoma.
5. antitumor action mechanism: glycyrrhizin have and strengthens nitric oxide generation effect in the mouse macrophage, this effect has obvious effect to suppressing tumor proliferation, glycyrrhizin causes macrophage, and (LPS) stimulates the generation nitric oxide with lipopolysaccharide, and suppresses tumor proliferation.
6. Radix Glycyrrhizae complex (LX) all has protection and Detoxication to the heart, liver, kidney, endocrine gland; various toxin and drug-induced arrhythmia have protective effect; cardiac contractile force is strengthened, lesions of liver and kidney due to various medicines and the toxin is had protective effect, anti-injury effect.
(4) the contained active acidic polysaccharose class of Pinus tabuliformis fruit.
1. to immune influence:
The extract of Parvifiorb Sieb et Zucc has the panimmunity activity, polysaccharose substance can activate that mice is huge to bite the drizzle born of the same parents, the hot water extract can improve the FC receptor active, acidic polysaccharose energy significant stimulation mice, the red born of the same parents DNA's of isolated rat spleen is synthetic, and the dialogue cell DNA synthesizes also certain stimulation.Acidic polysaccharose has immunologic enhancement.
2. anti-AIDS-virus effect:
The extract PC6 of Pinus Parvitora Sieb et Zucc receives through experiment in vitro, can suppress duplicating of HIV, cem cell to the HIV-1 that infects, PC6 all can suppress duplicating of HIV-1 according to dosage, virus breeding is suppressed, the 3mg/ml Cmin suppresses effect and reaches 80%, HIV in the U937 human lymphocyte-1 is also shown the obvious suppression effect, PC6 can suppress the proteic expression of HIV-1, but HIV-1 albumen for post-transcriptional level does not have obvious influence, PC6 can suppress the proteic expression of HIV-1, but HIV-1 albumen that participates in post-transcriptional level does not have obvious influence, PC6 can suppress HIV-1 transcribing and translating in cem cell, and gene expression also has inhibitory action to LTR guiding DNA at transcriptional level.Other has report: PC6 can produce a kind of solable matter to the pepsin sensitivity by inducing T cell (CEM), this material is that PC6 produces the reason that inhibition HIV-1 duplicates effect, (GM-CSF), (TGF-B1) (TNF-a) antagonism HIV-1 all has synergism to cytokine-3 (IL-3) B-transforming factor with a tumor necrosis factor for this PC6 inductive HIV-1 inhibitive factor and known granular leukocyte macrophage activity factor.Inductive this anti-HIV-1 material of PC6 may be a kind of new immunologic active material.
3. antitumor action:
The acidic polysaccharose that extracts among the Parvifiora Sied et Zucc has antitumor action, can rely on sarcoma and the ascites cells growth that ground suppresses to implant mice according to dosage, significantly prolong the normal mice time-to-live, antitumor size acid intensity is relevant, the acidic polysaccharose of NaoH extract, anti-tumor activity is the strongest, the most obvious inhibition sarcoma cell growth, even cause tumour regression and necrosis.The contained lignin thing of Pinus tabuliformis has inhibitory action to the activity of hyperplasia enzyme system in the mouse breast cancer, 175mg/0.1Mi \ 0.9% saline, I, V, the close phonetic deoxynucleoside acid enzyme of thymus, the close noisy deoxynucleoside kinases of thymus etc. in the ill SHV mouse tumor cell is had remarkable reduction active function.Prevent that simultaneously tumor from festering, prevent the outgrowth growth of breast nodule, growth again.Essence have necessarily does the cancer activity.
4. loose extract heavy dose is used animal sleep and anesthesia.Fruit is oral systemic allergic report.
(5) in sum: 1, antitumaous effect: Radix Phytolaccae polysaccharide saponin: ricin; Glycyrrhizic acid, Saponin, flavone, polysaccharide; The contained active polysaccharide of strobile, acidic polysaccharose all have synergism anticancer, anti-tumor activity, behind the cell binding site of the B chain that discharges after strobile acid polysaccharide and the cracking of glycyrrhizic acid sealing ricin, have the strong target cell lethal effect of high special.2, anti AIDS virus (HIV-1) effect: the extraction composition anti-HIV-1 of four medicines has synergism.3, immunoregulation effect (two-ways regulation, inhibitory reaction, immunological enhancement) is arranged.4, Radix Glycyrrhizae has Detoxication: Radix Glycyrrhizae extraction complex LX can remove ricin strong allergy such as cardiovascular, respiratory system, skin is returned reaction; Radix Glycyrrhizae is extracted the protective effect that LX can protect the heart, liver, kidney vascular tissue, regulate arrhythmia and respiratory system; can remove the inhibition of ricin to leukocyte, lymphocyte, respiratory function; and can reduce the cell oxygen consumption, increase the Cellular respiration function.Glycyrrhizic acid prevents the damage of ricin to hepatocellular destruction and small intestinal.Glycyrrhizic acid can be protected cerebral tissue; hemorrhagic necrosis and degeneration take place in adrenal gland, hypophysis, thymus, testis, ovary, pancreas and lymphoid tissue etc.; can also protect reticuloendothelial system, neuroganglion, thoracic wall from nervus peripheralis nuclei dyeing chromaticness destroy, and very strong guarantor's kidney and anti-injury function are arranged.
Claims (4)
1, a kind of medicament for the treatment of acquired immune deficiency syndrome (AIDS) and tumor is characterized in that its prescription is made up of Semen Ricini, Radix Phytolaccae, Radix Glycyrrhizae, strobile.
2, a kind of medicaments preparation method for the treatment of acquired immune deficiency syndrome (AIDS) and tumor is characterized in that processing step is as follows:
(1), ricin extraction process: peel off the outer duricrust of Semen Ricini earlier, white core pestle is become pasty state, remove Oleum Ricini
(1), centrifugal after 3 times of amounts of adding below 12 ℃ ethanol soak 4 hours, get its precipitation, pinch moltenly with water, the aqueous solution lyophilization promptly gets semifinished product, semifinished product aqueous solution filtering insoluble matter, add an amount of ethanol, place a moment, the filtering precipitation, mother solution adds small amount of ethanol again to little apparent muddiness, put and separate out crystallization in the refrigerator, in case of necessity recrystallization again;
(2), ethanol precipitation classification: Semen Ricini is stuck with paste and adds 3 times of amount ethanol, has precipitation to separate out centrifugal removing; Add 1 times of amount ethanol in this mother solution again, this partly precipitated of centrifugal collection, but still impure, add 1 times of amount ethanol in this mother solution again, the protein of then separating out is purer, and precipitation is used water dissolution, and lyophilization gets product;
(3), injection lactobionic acid ricin is dry and cold freezes crystalline producing: require aforementioned lipidated protein to reach 99.9% when above, with water dissolution, method purification secondary with DEAE-cellulose chromatography promptly gets pure product crystallization, adds the vacuum lyophilization of 0.1M galactobionic acid Galactonic acid promptly; The pure product ricin of gained, must 100% do not contain Semen Ricini because of and ricidine.;
(2), (1). the phytolaccatoxin extraction process:
Radix Phytolaccae thin slice extracting in water three times adds 8 times of amounts for the first time, boils filtration in 4 hours, second and third time adds 4 times of water gagings, boils 2 hours, and filtration, filtrate merge, concentrate the quintuple of ending medicine, get concentrated sulphuric acid and slowly be added in the concentrated solution, the limit edged stirs, concentrated solution 1000ml adds sulphuric acid 40g, after adding, boil to little and boiled 4 hours, put cold, pour in the equivalent cold water, stir evenly, placement is spent the night, abandoning supernatant, residual liquid is a sedimentation and filtration, precipitation wash with water to pH value be about 6, filter collection precipitation is drained, to dry below 60 ℃, the crude product phytolaccanine had both been got;
(2). the Radix Phytolaccae polysaccharide extracting process:
The Radix Phytolaccae sheet adds 5 times of amounts of 75% ethanol 0.5NNaoH, and reflux 2 hours is extracted three times with method; Merging filtrate is condensed into cream, adds 95% ethanol and is stirred to precipitation then, spends the night, and filters, and reclaims ethanol, continuous 2 times; Add 2 times of amounts of water, with DEAE cellulose chromatography purification, column chromatography purification is 2 times continuously, gets pure Radix Phytolaccae polysaccharide PEP-1;
(3), injection glycyrrhizic acid extraction process:
Radix Glycyrrhizae powder is concentrated into original volume 1/5 filtration with 12 times of amount 0.5% ammonia seepages, effusion, and filtrate adds concentrated sulphuric acid to PH3, filters the precipitation of separating out, and washes 3 times, and is dry below 60 ℃, gets thick glycyrrhizic acid
Pure product glycyrrhizic acid extracts: with the thick glycyrrhizic acid 400g of aforementioned gained, add 4 times of amount industrial alcohol, reflux three hours, filter, filtrate adds 2 times of amount alcohol refluxs 2 times, merges backflow and adds the 10g active carbon, reflux decolour cooling half an hour, filtration, the logical ammonia of filtrate is to PH7-7.5, till no solid is separated out; Filter collection precipitation, with the small amount of ethanol washing, drying at room temperature gets ammonium glycyrrhizinate 250g, continues 80% ethanol with 4 times of amounts, and heating for dissolving is also used activated carbon decolorizing, cold filtration, filtrate concentrates, and separates out white crystals, is pure glycyrrhizic acid.
(4), the strobile acidic polysaccharose is purified:
(1), strobile cleans and to dry, and pulverizes coarse powder, 500g adds 0.5NNaoH solution 4000ml, soaks half an hour, decocts 1 hour, with 4 layers of filtered through gauze, the not good liquor of winning;
(2), medicinal residues are added 0.5NNaoH distilled water 3000ml, decocted 40 minutes, 4 layers of filtered through gauze, second not good liquor;
(3), medicinal residues add 0.5NNaoH distilled water solution 2000ml, decocted 40 minutes, 4 layers of filtered through gauze, liquid for the third time;
(4), the merging of aforementioned three times filtrate be condensed into syrupy shape, place, add 95% ethanol, with adding with being stirred to precipitation fully, placement is spent the night, and reclaims ethanol, and gained liquid is placed 4 hours after-filtration again, filtrate shortens cream into;
(5), extract is acidic polysaccharose, if make used for intravenous injection, again with water dissolution, with the DEAE cellulose chromatography secondarily purified both pure product;
(5), injection preparation process:
(1), the dry and cold crystalline substance that freezes of lactobionic acid ricin, refining every of the pure product of ricin contain 20mg and add the vacuum lyophilization of equivalent 0.1M galactose in addition promptly;
(2), the injection preparation of treatment acquired immune deficiency syndrome (AIDS) and tumor: every bottle contains Radix Phytolaccae acidic polysaccharose 500mg, strobile acidic polysaccharose 2000mg, glycyrrhizic acid 2500mg adds to 100ml with water for injection, sterilization promptly;
(3), freeze brilliant 20-60mg with aforementioned lactobionic acid ricin is dry and cold, add injection water 2-6ml, or amount adds in the injection of treatment acquired immune deficiency syndrome (AIDS) and tumor on demand;
(6), slow releasing capsule is produced: the pure product people of ricin consumption 1ml/kg/ day, the pure product of phytolaccatoxin, 1mg/kg/ day, Radix Phytolaccae polysaccharide 10mg/kg/ day, the pure product of phytolaccotoxin albumen, 1mg/kg/ day, strobile acidic polysaccharose 40mg/kg/ day, Radix Glycyrrhizae albumen 50mg/kg/ day; Calculate to extract 6 kinds of compositions by people 50kg body weight, everyone is ricin 50mg/50kg/ day day by day, phytolaccatoxin 50mg/50kg/ day, Radix Phytolaccae polysaccharide 500mg/50kg/ day, phytolaccotoxin albumen 50mg/50kg/ day, strobile acidic polysaccharose 2000mg/50kg/ day, glycyrrhizic acid 2500mg/50kg/ day, add up to 5150mg altogether, divide 12 No. 1 capsule dresses, each capsule dress 429mg.
3, the medicaments preparation method of treatment acquired immune deficiency syndrome (AIDS) as claimed in claim 2 and tumor, it is characterized in that the 2nd step can also be the salt classification sedimentation method in the described ricin extraction process: former pastel adds the degree of saturation of ammonium sulfate to 40%, so the precipitation color is darker, centrifugal removing; Mother solution adds the degree of saturation of ammonium sulfate to 50%, collects this partly precipitated, but impure; Mother solution adds ammonium sulfate to 75% saturation again, and the gained protein precipitation is purer.
4, the medicaments preparation method of treatment acquired immune deficiency syndrome (AIDS) as claimed in claim 2 and tumor, the also available Radix Glycyrrhizae extractum of extraction that it is characterized in that thick glycyrrhizic acid in the described injection glycyrrhizic acid extraction process extracts, method is as follows: Radix Glycyrrhizae extractum 3kg, heating for dissolving is in 36 premium on currency, be chilled to room temperature, cross the stirring limit and drip the 145ml concentrated sulphuric acid; Leave standstill a few hours after adding, filter collection precipitation, the water thorough washing in oven dry below 60 ℃, gets thick glycyrrhizic acid 1.2kg, and content is about 55%.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US6866875B2 (en) * | 2001-09-26 | 2005-03-15 | Tampa Bay Research Institute | Pine cone extracts and uses thereof |
| US7838046B2 (en) | 2001-09-26 | 2010-11-23 | Tampa Bay Research Institute | Plant extracts and uses thereof |
| CN104288156A (en) * | 2014-09-22 | 2015-01-21 | 新乡医学院 | Pharmaceutical composition for treating stomach cancer and application thereof |
| CN104353058A (en) * | 2014-10-14 | 2015-02-18 | 海南森瑞谱生命科学药业股份有限公司 | PAP (pokeweed antiviral protein) freeze-dried powder compounding agent and preparation method of thereof |
| CN107629140A (en) * | 2017-11-13 | 2018-01-26 | 李辉 | A kind of method of ionic liquid double-aqueous phase system extraction Goods-Flow Plan |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1174062A (en) * | 1997-07-18 | 1998-02-25 | 迟经惠 | Medicine ointment for esophagus cancer |
| CN1233725A (en) * | 1998-04-29 | 1999-11-03 | 家电宝实业有限公司 | Lamp with temp. control automatic protection circuit |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6866875B2 (en) * | 2001-09-26 | 2005-03-15 | Tampa Bay Research Institute | Pine cone extracts and uses thereof |
| US7338676B2 (en) | 2001-09-26 | 2008-03-04 | Tampa Bay Research Institute | Pine cone extracts and uses thereof |
| US7371417B2 (en) | 2001-09-26 | 2008-05-13 | Tampa Bay Research Institute | Pine cone extracts and uses thereof |
| US7838052B2 (en) | 2001-09-26 | 2010-11-23 | Tampa Bay Research Institute | Pine cone extracts and uses thereof |
| US7838046B2 (en) | 2001-09-26 | 2010-11-23 | Tampa Bay Research Institute | Plant extracts and uses thereof |
| CN104288156A (en) * | 2014-09-22 | 2015-01-21 | 新乡医学院 | Pharmaceutical composition for treating stomach cancer and application thereof |
| CN104288156B (en) * | 2014-09-22 | 2017-01-18 | 新乡医学院 | Pharmaceutical composition for treating stomach cancer and application thereof |
| CN104353058A (en) * | 2014-10-14 | 2015-02-18 | 海南森瑞谱生命科学药业股份有限公司 | PAP (pokeweed antiviral protein) freeze-dried powder compounding agent and preparation method of thereof |
| CN107629140A (en) * | 2017-11-13 | 2018-01-26 | 李辉 | A kind of method of ionic liquid double-aqueous phase system extraction Goods-Flow Plan |
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| CN1102066C (en) | 2003-02-26 |
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