CN1853651A - Medicinal composition containing cinnabar or/and realgar - Google Patents
Medicinal composition containing cinnabar or/and realgar Download PDFInfo
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- CN1853651A CN1853651A CN 200610200273 CN200610200273A CN1853651A CN 1853651 A CN1853651 A CN 1853651A CN 200610200273 CN200610200273 CN 200610200273 CN 200610200273 A CN200610200273 A CN 200610200273A CN 1853651 A CN1853651 A CN 1853651A
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Abstract
A composite medicine containing the cinnabar and/or realgar is disclosed. It features that said cinnabar and/or realgar has been treated by bacterial method for converting the water-insoluble components to the water-soluble ones, resulting in high curative effect and no or low poison.
Description
Technical field
The present invention relates to contain the pharmaceutical composition of Cinnabaris and/or Realgar, say it is in pharmaceutical composition, to have used the Cinnabaris and/or the Realgar of dissolving and having removed harmful heavy metal definitely, be prepared into the pharmaceutical composition that contains Cinnabaris and/or Realgar through microbial method.
Background technology
Cinnabaris (cinnabaris) has another name called cinnabar, cinnabar.Its chemical constituent is mainly cinnabar (HgS), 25 kinds of trace element such as in addition, Cinnabaris is still leaded, barium, magnesium, ferrum, zinc, manganese.The Cinnabaris sweet in the mouth is slightly cold, and it is relieving convulsion to clear away heart-fire, the detoxifcation of calming the nerves.Be used for palpitation and being susceptible to fright, insomnia and dreamful sleep, epilepsy is gone mad, infantile convulsion, blurring of vision, aphtha, sore throat, sore swollen toxin.Because Cinnabaris has curative effect preferably, the successive dynasties, the medicine scholar created many name sides, used the prescription of Cinnabaris constantly to increase, and was widely used.Often use clinically contain the Cinnabaris prescription, patent medicine has tens kinds, wherein has famous and precious Chinese patent medicines, particularly Cinnabaris such as cow-bezoar bolus for resurrection, Bezoar Sedative Pills, ZIXUEDAN, most valuable treasure DANJI Cinnabar Sedative Pill particularly general with using in the Chinese patent medicine children's." formulary of peaceful benevolent dispensary " records prescription 788 altogether, prescription 82 sides that Cinnabaris is arranged, " pediatrics " records prescription 2271 sides altogether, prescription 206 sides that Cinnabaris is arranged, 398 kinds in the 4th edition Chinese patent medicine that the Pharmacopoeia of the People's Republic of China records and preparation, wherein have Cinnabaris, Realgar side's medicine to account for 54 kinds, singly containing Cinnabaris is 47 kinds, and Cinnabaris class side medicine preparation is occupying critical role aspect China's medicine for treatment.
Realgar (Realgar) beginning is stated from Mawangdui book copied on silk " 52 Bingfang ", another name gold stone, orpiment, dark yellow, Realgar, red orpiment, waist Huang, realgar.Its main component is As
2S
2(or As
4S
4), contain various trace elements in addition.Realgar acrid in the mouth, warm in nature, poisonous.Return liver, large intestine channel, have the effect of removing dampness and eliminating phlegm, detoxifcation parasite killing, preventing the attack (or recurrence) of malaria.Be applicable to the carbuncle furuncle, snake bite and insect sting, abdominal pain due to worm stagnation, diseases such as malaria.In the prescription of famous Chinese patent medicine LIUSHEN WAN, cow-bezoar bolus for resurrection, most valuable treasure ball, zijin troche etc. Realgar is arranged all.
Cinnabaris and Realgar extensively are used as medicine, but because the two all contains the heavy metal class harmful components and the arsenic of excess, this is restricted them in the use, particularly since the eighties in last century, international community is to heavy metal strong reaction in the Chinese patent medicine of China's outlet, even they directly are considered as poisonous substance, and (HgS) is considered as hydrargyrum Cinnabaris, Realgar (As
2S
2) be considered as arsenic (As) or arsenicum (As
2O
3), formulated strict standard simultaneously, content of beary metal such as the hydrargyrum in the restriction Chinese patent medicine, arsenic.
Chinese medicine pharmacopeia regulation is concocted Cinnabaris and Realgar with elutriation, not only time-consuming, the effort, the power consumption, and produce pollution such as waste gas waste water, the more important thing is since Cinnabaris and Realgar all the utmost point be insoluble in water, adopt these class methods can not effectively remove heavy metal and arsenic in the medicine, cause the excess of Cinnabaris and Realgar to use, and can't quantitatively control the content of active ingredient in the medicine, thereby limited the use of Cinnabaris and Realgar, and the Chinese patent medicine that contains Cinnabaris or Realgar moves towards internationalization and secondary development.
Adopting chemical separation technology is the heavy metal composition that can remove fully in the relevant mineral medicine, but facts have proved that these methods are difficult to keep necessary effective ingredient in the mineral medicine, thereby loses the therapeutical effect of Chinese medicine; On the other hand, adopt the pure chemistry method to carry out the composition that drug treating also may not had medicine itself, even poisonous and hypertoxic composition is introduced in the medicine, for avoiding this phenomenon to take place, not only need the technological measure of being correlated with, cause the drug treating cost to improve, be difficult to that these are added composition and remove clean.
We disclose the bacterial treatment method of mineral Chinese medicines such as Cinnabaris and Realgar in patent of invention 2006102000675, provide a class to adopt Cinnabaris that bacterial treatment method concocts and/or the pharmaceutical composition of Realgar among the present invention, because Cinnabaris that Cinnabaris of concocting with bacterial treatment method and/or Realgar are equal on drug effect or are better than concocting with elutriation and/or the drug effect of Realgar, and Cinnabaris and/or Realgar all can be removed harmful heavy metal or arsenic, selected for use the pharmaceutical composition of the Cinnabaris concocted with bacterial treatment method and/or Realgar on curative effect, to make moderate progress or strengthen, and the use amount of Cinnabaris and/or Realgar reduces; The content of harmful heavy metal or arsenic reduces, and toxic and side effects reduces.
Summary of the invention
For the Chinese traditional patent formulation that contains Cinnabaris and/or Realgar that had gone on the market already, because the shortcoming of prior art, use amount is big, the content height of poisonous metal or arsenic, thereby abroad piped off, and can't enter the foreign market.Enforcement of the present invention is that the Cinnabaris among the former side of existing listing finished product Chinese medicine and/or Realgar are replaced to Cinnabaris and/or Realgar with disclosed technical finesse in the patent of invention 2006102000675, thereby make this class contain the pharmaceutical composition of concocting with the processing of antibacterial method good drug effect is arranged promptly, reached low toxicity or nontoxic medication requirement again.
Owing to adopt disclosed technical finesse Cinnabaris and Realgar in the patent of invention 2006102000675, realized effectively to control the standard of the content of the onset composition of Cinnabaris and Realgar and harmful heavy metal or arsenic, thereby can conveniently carry out Cinnabaris and/or Realgar and existing Chinese medicine is composite to the human body safe medication.Because after treatment Cinnabaris and/or Realgar become solvable state by insoluble state, and then can handle the Cinnabaris of the process of preparing Chinese medicine and/or the drug regimen of Realgar with containing the antibacterial method easily, by " standard that Chinese pharmacopoeia is 2000 editions is made various preparations: suppository, pill, granule, membrane, microcapsule, drop pill, aerosol, medicated wine, syrup, oral liquid, injection or injection powder injection, these medicines except keep original indication, drug effect more remarkable, also can be used for treating diseases such as coma due to high fever, apoplexy, antitumor.
The specific embodiment
Six specific embodiments of the present invention below are provided, but this is not intended that the invention be limited to these concrete embodiments, because the same domain technical staff can use the present invention used Cinnabaris and/or the Realgar of concocting with the antibacterial method to carry out prescription according to this professional general knowledge.
Embodiment one
Adopt the Realgar A of disclosed technical finesse in our patent of invention 2006102000675 and the Realgar B that elutriation is handled,, see Table 1 chmice acute toxicity test result.
Table 1. acute toxicity test in mice result
| Mineral drug | Various processing methods | LD50 (95% average fiducial limit) i.g. |
| Cinnabaris | Former powder | 2.98g/kg±0.37g/kg |
| Cinnabaris | Process and add water and fly | 10.16g/kg±0.59g/kg |
| Cinnabaris | The present invention | 40.28g/kg±2.50g/kg |
| Realgar | Former powder | 3.86g/kg±0.61g/kg |
| Realgar | Process and add water and fly | 12.58g/kg±0.32g/kg |
| Realgar | The present invention | 70.68g/kg±2.80g/kg |
Embodiment two
The Cinnabaris and the Cinnabaris of Realgar and prior art processing and the Calculus Bovis peace palace ball of Realgar that add disclosed technical finesse in the not commensurability employing patent of invention 2006102000675; the influence long-pending: 40 of SD rats to middle cerebral artery thromboembolism rat cerebral infarction; be divided into 4 groups; every group 10; by body weight ig administration 1.0ml/100g; matched group and model group give equal-volume water, successive administration 3 days.After administration in second day 1 hour, cause rat brain focal ischemia with the tri-chlorination iron processes, measure the cerebral infarct size of rat, the results are shown in Table 2.
Table 2
| Experimental group | Dosage g/kg | The animal number of elements | Infarct size % |
| Matched group | 0 | 10 | 0.02±0.05 |
| Model group | 0 | 10 | 4.73±2.80 |
| Former cow-bezoar bolus for resurrection | 0.75 | 10 | 3.10±2.10 |
| Cow-bezoar bolus for resurrection of the present invention | 0.75 | 10 | 2.39±1.30 |
Embodiment three
Add the Cinnabaris of disclosed technical finesse in the not commensurability employing patent of invention 2006102000675 and Realgar (every 100ml contain the mercurous total amount of handling with the antibacterial method be 0.005% Cinnabaris and to contain the arsenic total amount be 0.005% Realgar) QINGKAILING KOUFUYE, matched group and model group give equal-volume water, and gastric infusion is 3 days continuously.After administration in second day 1 hour, cause rat brain focal ischemia with the tri-chlorination iron processes, measure the cerebral infarct size of rat, the results are shown in Table 3.
Table 3.
| Experimental group | Dosage ml/100g | The animal number of elements | Infarct size % |
| Matched group | 5 | 0.02±0.03 | |
| Model group | 5 | 4.60±2.10 | |
| QINGKAILING KOUFUYE | 0.2* | 5 | 3.20±1.98 |
| Of the present invention group | 0.2* | 5 | 2.63±2.30 |
* be diluted to 1.5ml
Embodiment four
The cow-bezoar anti-toxic bolus sheet of the Realgar that the Realgar (every 100g contains with what the antibacterial method was handled and contains the Realgar that the arsenic total amount is 0.005% (e) and 0.01% (f)) that adds disclosed technical finesse in the not commensurability employing patent of invention 2006102000675 and prior art are handled causes the antipyretic influence that rat paw edema and dinitrophenol cause rat fever to Ovum Gallus domesticus album.
1, Ovum Gallus domesticus album is caused the influence of rat paw edema
40 of rats, body weight 200g-250g, male and female half and half, be divided into 4 groups at random, the ig administration once a day, continuous 4 days, cause the scorching preceding every Mus ig of elder generation water 5ml, press the following position of ankle joint, capillary tube measurement by magnification method survey rat left side foot volume, repeat administration is once injected fresh albumen 0.1ml under the ankle joint aponeurosis (aponeuroses) of the every Mus of a 30min left side after the administration and is caused inflammation then, then every 1 hour each sufficient volume in a Mus left side of replication, continuous 4h, the difference that causes volume before scorching back different time sufficient volume in a left side and the administration with each Mus the results are shown in Table 4 as the swelling degree.
Table 4.
| Experimental group | Dosage g/kg | Paw swelling ml | |||
| 1h | 2h | 3h | 4h | ||
| Matched group | 0 | 0.63±0.09 | 0.62±0.10 | 0.60±0.12 | 0.63±0.13 |
| Detoxicating tablet of cow-bezoar | 1.7 | 0.50±0.11 | 0.49±0.13 | 0.48±0.10 | 0.43±0.11 |
| Detoxicating tablet of cow-bezoar e | 1.7 | 0.40±0.08 | 0.44±0.09 | 0.46±0.12 | 0.42±0.11 |
| Detoxicating tablet of cow-bezoar f | 1.7 | 0.44±0.11 | 0.38±0.10 | 0.36±0.09 | 0.30±0.13 |
2, dinitrophenol causes the antipyretic influence of rat fever
50 of rats are divided into 4 groups at random, after the preceding normal anus temperature of survey administration, the dinitrophenol alcoholic solution 40mg/kg pyrogenicity of every Mus dorsal part subcutaneous injection 2%, ig administration behind the 30min, every 30min surveys the anus temperature once after the administration, METHOD FOR CONTINUOUS DETERMINATION 2h, the record anus temperature value that detects the results are shown in Table 5.
Table 5
| Experimental group | Dosage g/kg | Anus temperature ℃ | ||||
| 30min | 60min | 90min | 120min | 240min | ||
| The blank group | 0 | 37.2±0.55 | 37.4±0.61 | 37.1±0.51 | 37.8±0.82 | 37.5±0.88 |
| Positive controls | 0 | 38.6±0.37 | 39.1±0.45 | 39.9±0.81 | 40.2±0.91 | 41.1±0.78 |
| Detoxicating tablet of cow-bezoar | 1.7 | 38.2±0.71 | 37.9±0.74 | 37.6±0.83 | 38.0±0.52 | 37.6±0.67 |
| Detoxicating tablet of cow-bezoar e | 1.7 | 37.6±0.81 | 37.4±0.95 | 37.9±0.73 | 37.7±0.77 | 38.0±0.69 |
| Detoxicating tablet of cow-bezoar f | 1.7 | 37.8±0.91 | 38.1±0.99 | 37.3±0.99 | 37.9±0.85 | 37.5±0.84 |
Embodiment five
The Cinnabar Sedative Pill of the Cinnabaris that the Cinnabaris (it is 0.00596 Cinnabaris that every 100g contains the mercurous total amount of handling with the antibacterial method) that adds disclosed technical finesse in the not commensurability employing patent of invention 2006102000675 and prior art are handled is to the influence of domestic cat wake cycle.
10 of rats are divided into two groups, adopt eight road electroencephalographs, the following index of continuous 6 hour records of 10:00 to 16:00 every day: electromyogram, ocular movement electrograph, cerebral cortex electrograph and lateral geniculate body discharge, continuous record was averaged in 4 days.The result is divided into the cat sleep-waking cycle according to record: lucid interval (w), prolongation S sleep I phase (SWSI), S sleep II phase (SWS II) and paradoxical sleep (PS) the results are shown in Table 6 before and after the administration.
Table 6
| Grouping | Handle | Sleep--the time phase (min) of-wake cycle | ||||
| W | SWSI | SWS II | PS | Total sleep time min | ||
| Cinnabar Sedative Pill | Before the administration | 261.4±4.1 | 37.6±6.5 | 45.3±7.8 | 18.4±4.9 | 101.3 |
| After the administration | 190.6±9.6 | 100.5±5.9 | 47.2±3.5 | 23.1±8.3 | 170.8 | |
| Anshen Wan of the present invention | Before the administration | 259.5±5.1 | 36.9±7.2 | 44.5±5.8 | 20.9±6.7 | 102.3 |
| After the administration | 187.9±6.1 | 106.7±8.5 | 45.9±4.9 | 19.0±5.4 | 171.6 | |
Embodiment six
1, the injection or the preparation of injection that contain Cinnabaris and/or Realgar:
Its preparation technology comprises the steps: that (1) get the Cinnabaris or the Realgar of recipe quantity respectively, and discloses Cinnabaris according to Chinese invention patent application 2006102000675, and the dissolving method of Realgar dissolves it, and centering metal (containing arsenic) content is controlled.The microorganism lysate for preparing Cinnabaris, Realgar carries out solid-liquid separation.(2) 5000 rev/mins after centrifugal 20 minutes, supernatant obtains containing the preparation liquid of Cinnabaris and/or Realgar key component with thalline and pyrogen material thereof in the microporous filter membrane filtering supernatant; (3) do not contain Cinnabaris with in the preparation liquid of variable concentrations and the prescription that makes by above-mentioned technology respectively, Realgar composition reserve liquid is pressed the mixed shown in the table one; (4) again behind filtering with microporous membrane, obtain containing Cinnabaris and/or Realgar spares; Contain Cinnabaris and/or the Realgar spares that (5) will make add in the injection reserve liquid of ready prepd Calculus Bovis peace palace (not containing Cinnabaris and/or Realgar) and are prepared into injection; (6) or lyophilization or spray drying promptly get powder ampoule agent for injection; (7) Calculus Bovis peace palace medicinal composition for injections is pressed following formulation:
First: a kind of Calculus Bovis peace palace medicinal composition for injections that contains Cinnabaris and/or Realgar is to form by following weight ratio: Calculus Bovis peace palace injection reserve liquid 0～99%+ Realgar component 1～100%.
Second: a kind of Calculus Bovis peace palace medicinal composition for injections that contains Cinnabaris and/or Realgar is to form by following weight ratio: Calculus Bovis peace palace injection reserve liquid 0～99%+ Cinnabaris component 1～100%
Third: a kind of Calculus Bovis peace palace medicinal composition for injections that contains Cinnabaris and/or Realgar is to form by following weight ratio: Calculus Bovis peace palace injection reserve liquid 1～99%+ Cinnabaris component 1～99%+ Realgar component 1～99%.
2, the antitumor action that contains the Calculus Bovis peace palace medicinal composition for injections of Cinnabaris and/or Realgar
1, materials and methods
(1) method shown in the embodiment one of pressing is pressed the various samples of table one preparation by clinical preceding new drug research key lab of Lanzhou University, all with 1mmol/L NaOH solution hydrotropy, transfers to desired concn with culture fluid.
(2) HL-60 cell line (people's acute promyelocytic leukemia cell is provided by preclinical medicine institute of Lanzhou University) is hatched in 37 ℃, 5%CO
2CO2 gas incubator in.With the RPMI RPMI-1640 that contains 10% calf serum (SIGMA company) cultivation of going down to posterity in per 2～3 days.
(3) respectively the medicinal liquid adding of different samples is covered with in the exponential phase cell of monolayer, act on after the different time with 0.25% trypsinization, collect the attached cell after each medicinal liquid effect, with PBS buffer washing 2 times, remove supernatant after centrifugal, splash into 70% cold ethanol fixed cell, 4 ℃ of preservations while vibrating.The PBS washing is 3 times before the last machine, add an amount of PBS liquid and contain the propidium iodide PI dye liquor mixing of RNA enzyme, after 45 order nylon wires filter, transfer cell concentration to 1 * 106/ml, with the variation of cells were tested by flow cytometry hypodiploid cell DNA content, measuring cell number is 10000.
(4) result of the test sees Table 7
Table 7
| The compatibility numbering | Time | The apoptotic cell ratio |
| The contrast reserve liquid | 6h | 0～0.86 |
| 24h | 0～0.98 | |
| First | 6h | 1.15～3.15 |
| 24h | 8.36～18.56 | |
| Second | 6h | 2.21～3.68 |
| 24h | 4.93～9.67 | |
| Third | 6h | 3.66～7.86 |
| 24h | 16.56～35.35 |
Claims (7)
1. the pharmaceutical composition that contains Cinnabaris and/or Realgar is characterized in that using in this pharmaceutical composition Cinnabaris and/or Realgar that bacterial treatment method has been removed harmful heavy metal or arsenic.
2. the described pharmaceutical composition of claim 1 is characterized in that this pharmaceutical composition can contain 1～100% Cinnabaris, perhaps contains 1～100% Realgar, perhaps contains 1～99% Cinnabaris and 1～99% Realgar simultaneously.
3. the described pharmaceutical composition of claim 2 is characterized in that this pharmaceutical composition can be suppository, pill, granule, membrane, microcapsule, drop pill, aerosol, medicated wine, syrup, oral liquid.
4. the medicinal composition for injections that contains Cinnabaris and/or Realgar according to claim 1 is characterized in that the prescription of this pharmaceutical composition is as follows:
Numbering Cinnabaris (weight ratio) Realgar (weight ratio) Reserve liquid (weight ratio)
First 0 1-100％ 0-99％
Second 1-100％ 0 0-99％
Third 1-99％ 1-99％ 1-99％
5. the medicinal composition for injections that contains Cinnabaris and/or Realgar according to claim 4 is characterized in that each composition of this pharmaceutical composition prepares as follows:
Cinnabaris: according to disclosed Cinnabaris extract extracting method in the Chinese invention patent application 2006102000675 it is dissolved, carry out solid-liquid separation, obtain the Cinnabaris reserve liquid.
Realgar: according to disclosed Realgar extract extracting method in the Chinese invention patent application 2006102000675 it is dissolved, carry out solid-liquid separation, obtain the Realgar reserve liquid.
Compound product, patent medicine injection reserve liquid: by " Chinese pharmacopoeia is extracted the extracting solution that makes separately.
6. according to claim 4 and the 5 described medicinal composition for injections that contain Cinnabaris and/or Realgar, it is characterized in that this pharmaceutical composition contains compound product, patent medicine injection reserve liquid 0～99% and contains Cinnabaris 1～100%, perhaps contain Realgar 1～100%, perhaps contain Cinnabaris 1～99% and Realgar 1～99%.
7. according to the described medicinal composition for injections that contains Cinnabaris and/or Realgar of claim 4 to 6, it is characterized in that this pharmaceutical composition also can use in antineoplaston, also can be applicable to other treatment of diseases.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610200273 CN1853651A (en) | 2005-03-28 | 2006-03-27 | Medicinal composition containing cinnabar or/and realgar |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200510063962 | 2005-03-28 | ||
| CN200510063962.2 | 2005-03-28 | ||
| CN 200610200273 CN1853651A (en) | 2005-03-28 | 2006-03-27 | Medicinal composition containing cinnabar or/and realgar |
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| Publication Number | Publication Date |
|---|---|
| CN1853651A true CN1853651A (en) | 2006-11-01 |
Family
ID=37194305
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610200273 Pending CN1853651A (en) | 2005-03-28 | 2006-03-27 | Medicinal composition containing cinnabar or/and realgar |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101002800A (en) * | 2007-01-10 | 2007-07-25 | 兰州大学 | Medicine composition containing extract of cinnabar, and application thereof |
| CN101912415A (en) * | 2010-08-03 | 2010-12-15 | 北京同仁堂（亳州）饮片有限责任公司 | Method for processing cinnabar powder Chinese medicinal tablets |
| CN111760029A (en) * | 2019-04-02 | 2020-10-13 | 赵新 | Composition of medicinal prescription for treating tumor |
-
2006
- 2006-03-27 CN CN 200610200273 patent/CN1853651A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101002800A (en) * | 2007-01-10 | 2007-07-25 | 兰州大学 | Medicine composition containing extract of cinnabar, and application thereof |
| CN101002800B (en) * | 2007-01-10 | 2013-06-26 | 兰州大学 | Medicine composition containing extract of cinnabar, and application thereof |
| CN101912415A (en) * | 2010-08-03 | 2010-12-15 | 北京同仁堂（亳州）饮片有限责任公司 | Method for processing cinnabar powder Chinese medicinal tablets |
| CN101912415B (en) * | 2010-08-03 | 2013-06-26 | 北京同仁堂（亳州）饮片有限责任公司 | Method for processing cinnabar powder Chinese medicinal tablets |
| CN111760029A (en) * | 2019-04-02 | 2020-10-13 | 赵新 | Composition of medicinal prescription for treating tumor |
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Open date: 20061101 |