2 national essential drug ergot related national essential drug retail guidance price information
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Description of price category 479 62 ergotamine caffeine tablets ergotamine tartrate 1mg/ anhydrous caffeine 100mg*6 boxes (bottles) 15 chemical and biological products *△ Note:
1, and those marked with "*" in the remarks column in the table are representative products.
2. If "△" is marked in the remarks column for the specifications representing dosage forms in the table, the prices representing dosage forms and related specifications with a clear price difference are tentative prices.
Overview ergot, also known as ergot and rye black rice, is a sclerotium formed by ergot fungi parasitic in the ovaries of rye and other undergraduate plants. It tastes slightly bitter, flat and toxic. Six epimers have been proposed, among which ergonovine, ergotamine and ergotoxine are effective components. [ 1]?
4 ergot poisoning Large doses of ergotamine and ergotoxine can directly act on blood vessels, leading to blood flow stagnation, vascular embolism and necrosis.
4. 1 adverse reaction mechanism: large doses of ergotamine and ergotamine can directly act on blood vessels, causing them to contract, causing blood pressure to rise and heart rate to slow down; It can also damage capillary endothelium, leading to blood flow stagnation, vascular embolism and necrosis; It can also block the adrenaline response system and reverse the pressor effect of adrenaline. Ergodine has no such effect. [ 1]?
4.2 Clinical manifestations Early symptoms of acute poisoning are: obvious thirst, burning sensation in the upper abdomen, nausea, vomiting, diarrhea, and sometimes abdominal pain, headache, unconsciousness and coma. It is accompanied by epileptic spasm and collapse, followed by tension contraction. The attack caused the patient to lose consciousness, mental disorder, dysuria, hypothermia, elevated blood pressure and finally died of respiratory arrest. [ 1]?
4.3 What is the key point of ergot poisoning treatment [1]? ：
1. Detoxification: injection of apomorphine to induce vomiting, gastric lavage and catharsis.
2. Improve microcirculation: intramuscular injection of tolasulin 25mg, 4 ~ 6 times/d; Subcutaneous injection of papaverine hydrochloride 30 ~ 60 mg, 4 times a day.
3. intravenous drip of low molecular dextran 500ml,1~ 2/d.
4. Traditional Chinese medicine: fresh Pteris multifida 100g, juiced and taken with boiling water.
5 National Collection of Chinese Herbal Medicine: ergot 5. 1 Pinyin name màI Ji m?o.
5.2 ergot alias ergot, rye and black rice
5.3 The source is sclerotia formed by ergot. )Tul。 Ergotaceae ergot on the host plant. Harvest when the ears of wheat are yellow and ripe in summer and autumn. Dry in the shade or dry for later use.
5.4 Sexual taste is light and lukewarm. Toxic.
5.5 Function is mainly used to contract uterus and stop bleeding. Used for postpartum uterine bleeding (promoting uterine reset) and migraine.
5.6 Usage and Dosage Ergot is often made into fluid extract, injection and other applications. The usual dosage of fluid extract is 2 ~ 4 ml each time, 1 6 ~ 8 ml per day, 1 4 ml per day, 1 02 ml per day.
5.7 note (1) ergot microcephalus (Wallr. Tul, a fungus, is very similar to ergot. The main difference is that the head of the daughter produced by sclerotia is small, with a diameter less than 0.8 mm.
5.8 Excerpted from National Compilation of Chinese Herbal Medicine
6 Traditional Chinese Medicine: ergot 6. 1 from traditional Chinese medicine.
6.2 Pinyin name mà i ji m: o
6.3 English name Ergot
6.4 Ergot alias rye black rice, purple ergot.
6.5 Source of medicinal materials: sclerotia of ergot and ergot minor.
Latin animal and plant mineral name: ergot. )tul。 ; Ergot capitis. )Tul。
Harvest and storage: wheat is harvested when it is mature in summer and autumn, and dried in the shade. Should be kept intact, completely dry, sealed and stored in a dry, cool and dark place.
6.6 Original form: 1. The sclerotium of ergot is long and cylindrical, with horns at both ends, hard, (1030)mm×(27)mm, smooth, with longitudinal grooves, purple-black outside, lavender or grayish white inside, and each sclerotium produces 2030 daughter seats, and the petiole is curved and dark brown. The base is nearly spherical, with a diameter of 12mm and reddish brown. The capsule is completely buried in the substrate, and its orifice slightly protrudes from the surface of the substrate, with a diameter of (200250) μ m× (150175) μ m. Ascomycetes are long and cylindrical. (100 125)μm×(45) μ m, containing 8 ascospores. Ascomycetes are colorless filamentous, (5070) μ m×1μ m.
2. ergot microcephalus is very similar to ergot, the main difference is that the sclerotium is black and angular, and the head of the daughter is small and the diameter is less than 0.8 mm.
6.7 Ecological environment of habitat distribution: 1. Parasitic in the ovary of gramineous plants such as wheat.
2. Born in Euphorbia and other Gramineae plants.
Resource distribution: 1. Distributed in Northeast China, North China, Xinjiang, Jiangsu, Zhejiang, Sichuan and other places.
2. Distributed in northeast China and Inner Mongolia.
6.8 cultivation 1. Biological characteristics: ergot is a parasitic fungus, and the parasitic plants are Gramineae, Cyperaceae, Dianthus and Juncaceae. Sclerotinia sclerotiorum grows in warm and humid summer, and the suitable temperature for mycelium growth is 2426℃.
2. Cultivation techniques: ergot mainly obtains ergot (sclerotia) by inoculation on host plants, or obtains similar sclerotia and its effective components by fermentation and culture of mycelium. Ergot can also be obtained by inoculation culture, but it is labor-consuming and has low yield, so at present, industrialized submerged culture and fermentation technology are mostly used.
2. Isolation of1.strain: The pure strain of ergot was isolated from the natural collected wild sclerotia. At present, the excellent strain for fermentation culture is ergot Ce33 isolated from Euphorbia bicolor.
2.2. Technological process: strain → test tube slant spore culture → seed culture → fermentation culture → filtration, and ergonovine separation and extraction.
2.3. Culture method: The spore culture medium is sucrose 10%, aspartic acid 0. 1%, magnesium sulfate 0.03%, KH2PO40. 1%, agar 2%, distilled water, pH6.06.2, making an inclined plane, and inoculating strains, 2426.
The seed medium was 6% sucrose, 1% glutamic acid, 0.03% mgso4.7h2o, 40. 1% kh2po4 and tap water, and the pH was adjusted to 5.2. Add 100ml culture medium into a 500ml conical flask, inoculate slant strains, and culture on a rotary shaker at 2426℃ for 72 hours. The fermentation medium is sucrose 10%, glutamic acid 1.2%, mgso4.7h2o 0.03%, KH2PO40. 1%, soybean oil 0.5% and tap water, and the pH is adjusted to 7.5. 75L fermentation medium in 500L conical bottle, inoculation amount 5%, rotation at 2426℃ for 9 days.
3. Determination method: The ergot total alkaloids were extracted with sodium carbonate and chloroform. Ergodine was extracted and separated by ion exchange resin method.
6.9 Characterization (1) The sclerotium of ergot is spindle-shaped, straight or slightly arched, with three blunt edges, 14cm long and 27mm wide. The skin is grayish purple to deep purple with fine transverse cracks and longitudinal grooves. It is hard and brittle, easy to break, flat in cross section and slightly obtuse triangle. Its edge is a thin layer of deep purple tissue, and its interior is light brown and white to red, and sometimes a star-shaped dark line can be seen in the center. The gas is weak, and the taste is slightly sweet first, then spicy.
(2) The sclerotium of ergot capitatum is black and angular, about 6mm long and 0.7mm in diameter. I'm almost like ergot. It is best to be dry, large and uniform, with purple-brown color and white section.
Microscopic identification of ergot cross section: slightly triangular, the outer layer is a series of closely arranged dark purple hyphal cells, the cell wall and its contents are blood red when exposed to acid and blue purple when exposed to alkali (wheat red pigment reaction), and the inner part is composed of colorless hyphal cells with different thickness (called pseudoparenchyma), with a diameter of 3 12μm, a thick wall and strong refraction, and the cells in the central part are loose and have gaps, and the cell wall is composed of chitin. Does not contain starch granules and calcium oxalate crystals.
Quality mark This product contains total alkaloids, calculated by ergotoxine, not less than 0.2%; Water-soluble alkaloids, calculated by ergonovine, shall not be less than 0.03%.
6. 10 contains alkaloids, which can be divided into three categories. The first category is ergotoxine alkaloids, which are amide derivatives of ergotic acid, mainly including ergonovine, ergonovine, ergobutine, ergobutine and ergotinine. Ergodine, ergovaline, α ergocryptine, β ergocryptine, ergocornine, o 12' methyl α ergocryptine (O 12). O 12' methyl ergocorning (o 12' methyl ergocorning), ergobine (ergotine), ergotamine, ergonovine, ergostin, etc. The second category is the corresponding ergotoxoid alkaloids, which are amide derivatives of isoergotic acid, mainly including ergotoxine, ergotoxine, ergobutine, ergonin, ergotoxine, ergopeptide and ergoprenyl. α ergometrine, β ergometrine, ergometrine, o 12' methyl α ergometrine, O 12' methyl ergometrine (O65438+o 12' methyl ergometrine), ergometrine (ergometrine), ergotamine (ergotamine). The third category is clavulanic alkaloids, including agroclavine, 6,7,7 7secoagroclavine, elymoclavine, secaclavine, isosetoclavine, penniclavine and ribavirin.
In addition, ergosterol, ergothionine, and saikang acid) A, B, C, D, ergotic acid, 4,55 dimethyl caprylic acid, ergot pigments (AD, BD, CD, DD, AC, BC, CC), clavulabine, ergot lutein, sugars, fatty oils, etc.
6. Pharmacological effects of 11ergot1. Effect of stimulating uterus: ergot has the effect of stimulating uterine muscles, similar to the preparation of posterior pituitary gland, which directly acts on uterine muscles, but the effect is strong and lasting. More sensitive to pregnant uterus; A small amount of application in labor and postpartum has obvious effect, and even produces tension contractions. The fluid extract made from several wild ergot bacteria in China can promote the contraction of rabbit uterus in vitro and in vivo, and increase the uterine tension. The experiment of rabbit uterus in vitro shows that its effect on postpartum and pregnant uterus is stronger than that on non-pregnant uterus. Ergot contains many effective components, among which ergonovine has the strongest effect on uterus, followed by ergotamine. Among 13 1 ergot strains isolated from 12 host plants in China, 17 strain can produce ergot toxin on wheat medium, among which strain 3 is the best, which not only produces strong alkali, but also mainly produces ergot toxin. 2. Effect on cardiovascular system: ergotamine can contract peripheral vascular smooth muscle in vitro. In the whole animal, due to vasoconstriction, blood pressure rises and compensatory bradycardia occurs. Ergot poison has less influence on the heart than on blood vessels, but it can enhance the contractility of the heart when the heart rhythm slows down to a certain extent. Taking ergotamine in large quantities will damage vascular endothelial cells (the principle is unknown), leading to gangrene. Italian breeders (1.5 ml/kg) were injected with ergot fluid extract (23 times/day), and the cockscomb was cyanotic for a long time, and the cockscomb was gangrenous, which could establish conditioned reflex. Ergotamine has the strongest effect on blood vessels, followed by ergotoxine, which hardly affects blood pressure and damages vascular endothelial cells. Ergotamine can contract blood vessels and reduce the amplitude of arterial pulsation, which may be related to the treatment of migraine.
3. Effect on nervous system: A large amount of ergotamine or ergotoxine can block α adrenergic receptors and reverse the pressor effect of adrenaline. They can't stop the release of sympathetic mediators. The experimental results of guinea pig's isolated inferior vas deferens showed that ergonovine and norepinephrine had similar effects. The authors suggest that ergonovine may be a directly acting sympathomimetic drug, which acts on the same receptor as catecholamine. A small amount of ergot excites the medulla oblongata (vagus bradycardia, increased breathing, convulsions, etc.). ), and a large number of ergot died of cerebral palsy. Ergotamine can enhance the sedative and hypnotic effects of barbiturates, morphine and methadone. Parasitic on rye and grass. Leymus chinensis, Elymus sibiricus, wild ergot such as Elymus dahuricus. And agropyron cristatum. All of them have obvious effects of enhancing uterine contraction, among which the ergot fluid extract of Euphorbia humifusa, Elymus nutans and Thinopyrum repens has a slightly stronger effect.
6. Acute symptoms of12 poisoning are vomiting, diarrhea, weak pulse and coma. Chronic poisoning is seen in overdose, liver disease and peripheral vascular disease, and the symptoms are necrosis and convulsion.
6. Physical and chemical identification of 1 3 ergot (1) Take about 0. 1g powder, add 2ml of ether and1drop of dilute sulfuric acid, shake well, separate the ether solution, add a few drops of saturated sodium bicarbonate solution, shake well, and let stand. The lower aqueous solution is red or purple blue. (Check ergot red pigment) (2) Take a little powder, add sodium bicarbonate solution and chloroform * * * and shake well, separate chloroform solution, add a little p-dimethylaminobenzaldehyde test solution, shake well, and let stand until the reagent layer is blue. (Detection of ergot alkaloids) (3) Determination of ergot, ergotoxine, ergotamine and ergotamine; Degreasing ergot powder with petroleum ether (30 ~ 60℃), drying, accurately weighing 1g, placing in a 50ml brown flask with a stopper, and adding chloroform, methanol and ammonium hydroxide (90: 9: 65438+). Dissolve the residue with 0.25ml methanol, put 0. 1ml on alumina (weakly alkaline, 200 mesh, activity grade II-III) thin-layer plate, saturate 10min with benzene chloroform absolute ethanol (7: 3: 0.5), then unfold, observe the fluorescence under ultraviolet lamp, draw out the color band of alkaloids, and use suction collection. Add 4ml of 0.1.5mol/l sulfuric acid solution and reagent (0. 1.25 g of p-dimethylaminobenzaldehyde, add 65ml of nitrogen-free sulfuric acid and 35ml of distilled water to dissolve, and then add 0.05ml of 9% ferric chloride solution to mix well), shake well, and let stand for 30min.
6. 14 is bitter; Xin; Ping; Poisonous
6. 15 meridian-entering the liver; Kidney meridian
6. 16 function is mainly used for uterine contraction and hemostasis; Pain relief. Major uterine bleeding; migraine
6. 17 Administration and dosage of ergot orally: make into fluid extract, 0.5 ~ 2ml each time, 3 ~ 4 times a day; Large dose 1 time 4ml, daily12 ml; ; Or made into tablet and injection.
6. 18 Note 1. Pharmacology of traditional Chinese medicine: it can only be used in the squeezing period during childbirth, and should be avoided during laparotomy. It is forbidden when pregnant women, labor and placenta are not completely discharged. Use with caution in patients with liver disease and peripheral vascular disease. This product is toxic and often causes thirst, vomiting, diarrhea, cold limbs, pale face, impaired vision and hearing, and even hallucinations and convulsions in severe cases, leading to coma and death.
2. China medicinal fungi in Liu Bo: it is forbidden when the placenta is not discharged.
6. 19 Various expositions 1. Traditional Chinese medicine: it is a uterine contraction drug. It is effective for uterine bleeding, postpartum soft bleeding, uterine insufficiency, regression, etc.
2. Chinese herbal medicine treatment manual at high altitude: treating migraine.
6.20 Excerpted from Chinese Materia Medica
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