Celestial Fairy
1、 Pharmacopoeia standard of tianxianzi       This product is the dried and mature seed of Hyoscyamus niger L. When the peel turns yellow in summer and autumn, the fruit is picked, exposed to the sun, seeded, peeled and dried.
      [properties] this product is in the shape of flat kidney or flat egg, with a diameter of about 1mm. The surface is brownish yellow or grayish yellow, with fine reticulation, and the slightly pointed end has a punctate hilum. The cut surface is gray white, oily, with endosperm and curved embryo. The air is weak and the taste is pungent.
      [identification] (1) the powder of this product is grayish brown. There are many fragments of epidermal cells outside the seed coat, with yellow brown granules attached to the surface, irregular polygonal or long polygonal on the surface, and the vertical circumferential wall is wavy and curved; The side view shows wavy protrusions. Endosperm cells are round like, with vague powder particles and fatty oil droplets.
      (2) Take 1g of this product powder, add 10ml of petroleum ether (30 ～ 60 ℃), sonicate for 15 minutes, discard the petroleum ether solution, and treat again as above. Volatilize the solvent from the drug residue, add 2ml of ethanol concentrated ammonia test solution (1:1) mixed solution to wet, add 20ml of chloroform, sonicate for 15 minutes, filter, evaporate the filtrate, add 0.5ml of absolute ethanol to dissolve the residue, and use it as the test solution. . According to the test of thin-layer chromatography (general rule 0502), suck 5 μ l each of the above two solutions, dot them on the same silica gel G thin-layer plate, use ethyl acetate methanol concentrated ammonia test solution (17:2:1) as the developing agent, develop, take out, dry, and spray bismuth potassium iodide test solution and sodium nitrite ethanol test solution in turn. In the chromatogram of the test sample, there are two brown spots on the corresponding position of the chromatogram of the control sample.
      ; Not more than 8.0% (general rule 2302).
      Acid insoluble ash   Not more than 3.0% (general rule 2302).
      [content determination] determine according to HPLC (general rule 0512).
      Chromatographic conditions and system suitability test   Octadecylsilane bonded silica gel was used as filler; The mobile phase was methanol acetonitrile 30mmol / L sodium acetate buffer (containing 0.02% triethylamine, 0.3% tetrahydrofuran, adjusting the pH value to 6.0 with glacial acetic acid) (10:5:85); The detection wavelength was 210nm. The number of theoretical plates should not be less than 4000 according to the peak of hyoscyamine.
      Preparation of reference solution   Take an appropriate amount of scopolamine hydrobromide reference substance and atropine sulfate reference substance, weigh accurately, add methanol to make a mixed solution containing 0.17mg of scopolamine hydrobromide and 0.15mg of atropine sulfate per 1ml to obtain (scopolamine weight = scopolamine hydrobromide weight × 0.7894; scopolamine weight = atropine sulfate weight × 0.8551).
      Preparation of test solution   Take about 2G of this product powder (passing through No. 3 screen), weigh it accurately, put it in Soxhlet extractor, add an appropriate amount of petroleum ether (30-60 ℃), heat it for refluxing for 2 hours, discard the petroleum ether solution, volatilize the solvent from the drug residue, add an appropriate amount of methanol, heat it for refluxing for 6 hours, recover the extract solution to dryness under reduced pressure, add 25ml of concentrated ammonia test solution (8 → 100) to dissolve the residue, transfer it to the separatory funnel, wash the container and residue with a small amount of chloroform, incorporate it into the separatory funnel, extract it five times with chloroform, 15ml each time, combine the chloroform solution, recover it to dryness under reduced pressure, add absolute ethanol to dissolve the residue, transfer it to a 10ml volumetric flask, add absolute ethanol to the scale, shake well, and get it.
      Assay   Precisely suck 5 μ l of the reference solution and 5 μ l of the test solution respectively, inject them into the liquid chromatograph, and determine.
      The total amount of scopolamine (C17H21NO4) and scopolamine (c17h23no3) in this product shall not be less than 0.080% according to the dry product.
      [nature, taste and meridian tropism] bitter, pungent and warm; It is highly toxic. Homing, stomach and liver channels.
      [functions and indications] it can relieve spasm and pain, relieve asthma and calm nerves. It is used for epigastric contracture, wheezing cough and madness.
      [usage and dosage] 0.06 ～ 0.6g.
      [note] it is forbidden for patients with heart disease, tachycardia, glaucoma and pregnant women.
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2、 Chemical constituents of tianxianzi
1. hyoscyam seed containsHyoscyamine（hyoscyamine)0.02%-0.17%，Scopolamine; It also contains fat, up to 25%. The fatty acid group became:Myristic acid（myristic aicd)0.3%，palmitic acid（palmitic acid)6.5%， Stearic acid 1.6%, oleic acid 35.2%, linoleic acid 56.4%[3].
2. tianxianzi seeds contain 0.04% tianxianzi amine,Scopolamine0.01%[1]。

3、 Pharmacological effects of tianxianzi
1. effect on the circulatory system: 1.1. effect on the heart: scopolamine can relieve the inhibition of the vagus nerve on the heart, making sympathetic nerve dominant, so it can speed up the heart rate. Atropine has a similar effect and is stronger. Intravenous injection of atropine 2-3mg/kg or scopolamine 4mg/kg to rabbits and dogs can antagonize the arrhythmia induced by epinephrine or norepinephrine, but cannot antagonize the acceleration of heart rhythm caused by epinephrine or norepinephrine.
1.2. effects on blood vessels and hemodynamics: isolated rabbit vascular perfusion showed that scopolamine could antagonize the contraction induced by epinephrine, but it was weaker than atropine. At the same time, it could also antagonize the decrease of blood pressure caused by acetylcholine and improve microcirculation.
2. effects on central nerves: 2.1. effects on behavior: scopolamine injected into the lateral ventricle of rabbits can cause eye closure, lateral recumbency, righting reflex disappearance, activity reduction and other phenomena. Combined with hibernation mixture or pentobarbital can reduce the activity of animals, showing the synergistic effect with central inhibitors. However, it has been reported that a small dose of scopolamine can increase the spontaneous activity of mice, and can resist the decrease of activity caused by blood balance, showing the central excitatory effect. Therefore, the effect of scopolamine on the central nervous system is bidirectional.
2.2. effect on animal EEG: the awake cat was intraperitoneally injected with scopolamine hydrobromide 0.05-0.1mg/kg, and the EEG changed from low amplitude fast wave to irregular high amplitude slow wave, and the animal was quiet. When the dose was increased to 0.25-5mg/kg, the EEG showed highly synchronized and irregular high amplitude slow waves, at which time the animals showed excitement and mania. Scopolamine also has similar EEG responses to dogs, rabbits, rats and other animals, and can block the wake-up response caused by a variety of physiological stimuli.
2.3. effects on conditioned reflex: scopolamine can block avoidant conditioned reflex and secondary conditioned reflex in rats to varying degrees, and the blocking rate is parallel to the dose, while atropine has a weak effect.
2.4. effect on pain perception: the pain test of potassium ion penetration method in rabbits showed that the pain threshold increased by 49% 30 minutes after the intraperitoneal injection of scopolamine 4mg/kg. After intravenous injection of scopolamine at the same dose, the pain threshold increased by 37% 20 minutes after administration. However, the pain threshold increased by 53% 20 minutes after lateral brain injection of 5mg / mouse, 147% when combined with dolantin (60mg/kg intraperitoneal injection), and 93% when used alone, suggesting a synergistic effect of the two drugs. The hot plate test in mice showed that scopolamine 1.25mg/kg intraperitoneal injection increased the pain threshold by 62% 15 minutes after administration, and the pain threshold increased by 126% 15 minutes after administration when combined with small dose of cold Ding (10mg/kg intraperitoneal injection), while the pain threshold increased by only 23% when measured with small dose of cold Ding, which was consistent with the experimental results in rabbits. In addition, after injecting 20mg norepinephrine into the lateral ventricle of rabbits, the pain threshold decreased by 46% at 10 minutes, and the analgesic effect of pethidine was attenuated. Scopolamine Combined with norepinephrine can antagonize the anti analgesic effect of the latter. Therefore, it is presumed that the analgesic effect of scopolamine and the enhancement of the analgesic effect of meperidine may be related to its anti norepinephrine effect.
3. effects on glands and smooth muscle: atropine can inhibit the secretion of glands, and has a significant relaxation effect on smooth muscle under hyperactivity or spasticity.
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