CN114177204A - Preparation method of cobra traditional Chinese medicine raw powder - Google Patents
Preparation method of cobra traditional Chinese medicine raw powder Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/58—Reptiles
- A61K35/583—Snakes; Lizards, e.g. chameleons
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
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- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
- A61L2/0011—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using physical methods
- A61L2/0029—Radiation
- A61L2/0035—Gamma radiation
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Abstract
本发明公开了一种眼镜蛇中药生粉的制备方法，属于药粉炮制技术领域，包括以下步骤：粉碎：取眼镜蛇饮片，烘干至手感干燥，然后放入粉碎设备中进行粉碎，再放入超微粉碎设备中继续粉碎，得到细粉；灭菌：将上述S1得到的细粉采用辐照灭菌法进行灭菌，得到灭菌后的细粉；包装：将上述S2处理得到的细粉用药用复合膜包装，得到眼镜蛇药粉成品。该方法制备得到的眼镜蛇中药生粉细粉出粉率高、有效成分完整，其微生物限度符合《中国药典》2020年版四部通则非无菌产品微生物限度检查中药饮片微生物限度标准，其水分和总灰分符合《中国药典》2020年版四部通则0832第二法和《中国药典》2020年版四部通则2302规定。The invention discloses a preparation method of cobra traditional Chinese medicine raw powder, which belongs to the technical field of medicinal powder processing. Continue to pulverize in the pulverizing equipment to obtain fine powder; Sterilization: the fine powder obtained in the above S1 is sterilized by irradiation sterilization to obtain the fine powder after sterilization; Packaging: the fine powder obtained by the above-mentioned S2 treatment is used for medicinal purposes The composite film is packaged to obtain the finished product of Cobra medicinal powder. The cobra Chinese medicinal raw powder fine powder prepared by the method has high powder yield and complete effective components, and its microbial limit conforms to the microbial limit standard of the four general chapters of the Chinese Pharmacopoeia 2020 edition for non-sterile products. It complies with the second law of the 2020 edition of the Chinese Pharmacopoeia, the 4th General Principles 0832, and the 2020 edition of the Chinese Pharmacopoeia, the 4th General Principles 2302.
Description
Technical Field
The invention belongs to the technical field of medicine powder processing, and particularly relates to a preparation method of raw traditional Chinese medicine powder of cobras.
Background
Cobras are also called varicocephalus, bat snakes, five-toxin snakes and pipa snakes, and are animal cobras of the family Elapidae. The body is 1-2 m long and is thick; oval head, dark brown head and back, glasses-like stripes on neck, and yellowish white to grayish brown body back. Cheek scale free, anterior orbital scale 1, posterior orbital scale 2 or 3; temporo scale 2+3, upper lip scale 2-2-3; smooth descales, lines 23-21 (19) -15; 160-196 parts of abdominal scales; 2 minutes of anal scale and 38-54 pairs of caudal scales. The cobra is usually processed by removing internal organs, wiping blood, and fresh or dried. Cobra is collected in the standard of Chinese herbal medicine in 1 province and municipality autonomous region in China, and the processing method is detailed in Table 1.
TABLE 1 processing method and general list of receiving standards for cobra
The cobra decoction pieces are planned to be ground into fine powder for taking, so the grinding method and the powder yield of the fine powder are investigated and researched. Because the cortex of the cobra decoction pieces is difficult to break by adopting the conventional crushing equipment, the cortex components which are difficult to break are further subjected to superfine crushing on the basis of crude crushing of the decoction pieces so as to ensure the yield of fine powder and the integrity of the components. Meanwhile, the bacterial pollution of the raw traditional Chinese medicine powder is difficult to avoid, so that the raw traditional Chinese medicine powder needs to be further sterilized after being crushed.
The preparation method of the pure snake powder at present comprises the following steps: patent one (CN 201410510066.5), a pure snake powder and a preparation method thereof, discloses a preparation method of the pure snake powder, which is characterized by comprising the following steps: is prepared from health Zaocys or Agkistrodon acutus by removing head, killing, cutting abdomen, collecting viscera, cleaning, baking, pulverizing, and sieving. However, the pure snake powder obtained by the method is not sterilized, so that bacterial pollution is easily caused.
The second patent (CN 97106310.9), a composition of tortoise powder and snake powder and a preparation method thereof relate to a composition of tortoise powder and snake powder, the method of the composition of tortoise and snake is that tortoise and snake are eviscerated, sterilized by steam, dried at high temperature, and then the dried tortoise and snake raw materials are crushed into powder with the granularity below 80 meshes. The invention can enhance the physique of human body and improve the immunity of human body. The sterilization method is wet heat sterilization, but the method can damage the medicinal components of the snake powder.
Disclosure of Invention
Aiming at the problems in the prior art, the invention aims to provide a preparation method of raw cobra Chinese medicinal powder, the fine powder of the raw cobra Chinese medicinal powder prepared by the method has high powder yield and complete active ingredients, the microbial limit of the raw cobra Chinese medicinal powder meets the microbial limit standard of non-sterile products checked by the limit of microorganisms of the Chinese medicinal decoction pieces in the four-part general rules of 2020 edition in Chinese pharmacopoeia, and the water content and the total ash content of the raw cobra Chinese medicinal powder meet the second method 0832 in the four-part general rules of 2020 edition in Chinese pharmacopoeia and the 2302 in the four-part general rules of 2020 edition in Chinese pharmacopoeia.
In order to realize the purpose, the invention adopts the technical scheme that:
a preparation method of cobra traditional Chinese medicine raw powder comprises the following steps:
s1: crushing: oven drying cobra decoction pieces until the water content is below 7%, coarsely pulverizing in a pulverizing device, and further pulverizing in an ultra-fine pulverizing device to obtain fine powder;
s2: and (3) sterilization: sterilizing the fine powder obtained in the step S1 by adopting an irradiation sterilization method to obtain sterilized fine powder;
s3: packaging: packaging the fine powder obtained by the S2 treatment by using a medicinal composite film to obtain the finished product of the cobra medicinal powder.
Further, the drying temperature is 60-70 ℃.
Further, the crushing equipment is an FL-150 dust removal crusher.
Further, the superfine grinding equipment is a low-temperature superfine grinder TYM-16L.
Further, the particle size of the coarse pulverized powder is 40-50 meshes.
Further, the particle size of the fine powder is below 120 meshes.
Further, the radiation sterilization method is to adopt60Co-gamma irradiation sterilization method, the irradiation dose is 6 kGy.
Further, the medicinal composite membrane is polyester/aluminum foil/polyethylene.
The invention has the beneficial effects that: (1) the cobra Chinese medicine raw powder fine powder prepared by the method has high powder yield and complete active ingredients, the microbial limit of the cobra Chinese medicine raw powder fine powder accords with the microbial limit standard of non-sterile products checked by the microbial limit of Chinese medicine decoction pieces according to the four-part general rule of China pharmacopoeia 2020 edition, and the water content and the total ash content of the cobra Chinese medicine raw powder accord with the second method of 0832 of the four-part general rule of China pharmacopoeia 2020 edition and the 2302 of the four-part general rule of China pharmacopoeia 2020 edition;
(2) according to the invention, conventional grinding and superfine grinding are combined, the powder yield of fine powder can reach more than 90%, and the cortex of the cobra decoction pieces is difficult to break by adopting conventional grinding equipment, so that the cortex components which are difficult to break are further subjected to superfine grinding on the basis of crude grinding of the decoction pieces, so that the yield of the fine powder and the completeness of the components are ensured;
(3) the cobra powder prepared by the invention is crude medicinal powder, and the bacterial pollution of the crude Chinese medicinal powder is difficult to avoid, so that the product is sterilized by selecting an appropriate method; the current common sterilization methods comprise ultraviolet sterilization, damp-heat sterilization, microwave sterilization,60Co irradiation sterilization, etc.; ultraviolet sterilization is generally used for sterilization of the surface of an object and air; the wet heat sterilization method can sterilize raw medicinal materials, liquid preparations and the like, but the damage of sterilization to the effective components of the raw materials and the preparations with the effective components of heat-sensitive components needs to be inspected; the microwave sterilization is mainly used for sterilizing solid preparations such as liquid preparations, wet powders, honeyed pills, granules and the like, the sterilization time is short, heated substances are basically not overheated, the influence on effective components is small, and the effect is reliable, but the microwave sterilization has less ideal sterilization effect when being applied to mass production at present due to equipment and other reasons;60the Co irradiation sterilization method is cold sterilization, has strong penetrating power and no residue, is a better sterilization method, and is tested by adopting60Co-gamma irradiation sterilization with irradiation dose of 6kGy, polymerase chain reactionThe reaction can be detected, has no influence on nitrogen content basically, and meets the requirement of microbial limit;
(4) after long-term stability tests and accelerated stability tests, the cobra powder prepared by the invention is placed for 2 months under the conditions of 25 +/-2 ℃ and RH60% +/-10%, and is placed for 2 months under the conditions of 40 +/-2 ℃ and RH75% +/-5% for detection, all indexes meet the requirements of quality standards, and the quality of cobra powder samples is stable within 2 months;
(5) the cobra powder prepared by the invention is yellowish white powder, can be seen as black epidermis fragments, has slight fishy smell and light taste, and is microscopically characterized in that the powder is yellowish white, cutin scales are nearly colorless or light yellow, and the side surface of the cobra powder has semicircular or papillary protrusions; the surface is in a shape similar to a circle, an oval or a polygonal bulge, some of the bulges are arranged in a tile shape, some longitudinal cracks are invisible, and fine particles are distributed on the surface. The epidermis fragments are yellowish, the apparent cell boundaries of the surface are unclear, and dark brown pigment particles are distributed and aggregated into irregular networks or branches. The striated muscle fibers are colorless or yellowish, and have fine and dense striations with flat or microwave-shaped light and shade, and some are unclear. The bone fragments are light gray and are irregular blocks, the bone pits are crack-shaped or strip-shaped, most of the bone pits are arranged in the same direction, the bone tubules are thin, and fine oblique staggered textures are visible on the surface. The sample was visible as residual cuticle scales.
The cobra powder is used as a traditional Chinese medicine preparation:
[ PROPERTIES AND WEIGHT GUIDING GEN ] is sweet, salty and warm; is toxic. It enters liver and kidney meridians.
[ FUNCTIONS AND INDICATIONS ] can dredge meridians, dispel wind-damp, and alleviate pain. Treating rheumatic arthralgia and beriberi; hemiplegia and poliomyelitis.
[ DOSAGE AND ADMINISTRATION ] is administered orally 1-1.5 g at a time, 2-3 times a day.
[ PROFILE ] Per bag contain 1 g.
[ STORAGE ] sealing.
Drawings
FIG. 1 is a drawing of a real object of a snake tablet used in each of examples 1 to 3;
FIG. 2 is a diagram showing a substance of the cobra powder obtained in each of examples 1 to 3;
FIG. 3 is a microscopic characteristic diagram of cobra powder obtained in example 1;
FIG. 4 is a report sheet of the inspection of cobra powder obtained in example 2;
FIG. 5 is a gel electrophoresis chart of cobra powder and decoction pieces thereof in damp-heat sterilization and 60Co irradiation sterilization tests; the numbers marked in the map respectively correspond to the following contents: 1 is 100bp DNA Ladder; 2-the medicine is cobra decoction pieces-Guangxi; (ii) a 2- ② cobra powder-Guangxi (moist heat sterilization at 121 ℃ for 20 min); 3-the Chinese medicinal materials are cobra pieces-Xiangxi; 3- ② cobra powder-Xiangxi (moist heat sterilization at 121 deg.C for 20 min); 4-the raw materials are cobra decoction pieces-Yongzhou; 4- ② cobra powder-Yongzhou (sterilization by moist heat at 121 ℃ for 20 min); (iii) 2- (iii) cobra powder-Guangxi (moist heat sterilization at 126 deg.C for 15 min); 2-the four are cobra powder-Guangxi (radiation sterilization); 3- ③ to obtain cobra powder-Xiangxi (sterilization by moist heat at 126 ℃ for 15 min); 3-four is cobra powder-Xiangxi (radiation sterilization); (4- ③) cobra powder-Yongzhou (sterilization by moist heat at 126 ℃ for 15 min); 4-four is cobra powder-Yongzhou (irradiation sterilization); 5 is blank control; 6 is DL 2000 DNA marker
Detailed Description
For a better understanding of the present invention, embodiments of the present invention are described in detail below with reference to examples, but those skilled in the art will understand that the following examples are only for illustrating the present invention and should not be construed as limiting the scope of the present invention.
Example 1:
a preparation method of cobra traditional Chinese medicine raw powder comprises the following steps:
s1: crushing: weighing 300g of Guangxi producing area cobra decoction pieces, drying until the water content is 6%, wherein the drying temperature is 65 ℃, then putting the mixture into a FL-150 dust removal crusher for crushing, and then putting the crushed mixture into superfine crushing equipment for continuous crushing to obtain fine powder, wherein the particle size of the coarse crushed powder is 50 meshes, and the particle size of the fine powder is 110 meshes;
s2: and (3) sterilization: sterilizing the fine powder obtained in S1 by irradiation sterilization60Performing Co-gamma irradiation sterilization with irradiation dose of 6kGy to obtain sterilized fine powder;
s3: packaging: and packaging the fine powder obtained by the S2 treatment by using a polyester/aluminum foil/polyethylene medicinal composite film to obtain the cobra medicinal powder finished product.
Example 2:
a preparation method of cobra traditional Chinese medicine raw powder comprises the following steps:
s1: crushing: weighing 300g of Naja naja decoction pieces produced in Yongzhou producing areas, drying until the water content is 7%, wherein the drying temperature is 60 ℃, then putting the obtained product into a FL-150 dust removal crusher for crushing, putting the crushed product into superfine crushing equipment for continuous crushing to obtain fine powder, wherein the particle size of the coarse crushed powder is 40 meshes, and the particle size of the fine powder is 120 meshes;
s2: and (3) sterilization: sterilizing the fine powder obtained in S1 by irradiation sterilization60Performing Co-gamma irradiation sterilization with irradiation dose of 6kGy to obtain sterilized fine powder;
s3: packaging: and packaging the fine powder obtained by the S2 treatment by using a polyester/aluminum foil/polyethylene medicinal composite film to obtain the cobra medicinal powder finished product.
Example 3:
a preparation method of cobra traditional Chinese medicine raw powder comprises the following steps:
s1: crushing: weighing 300g of Hunan Xisheng cobra decoction pieces, drying until the water content is 7%, wherein the drying temperature is 70 ℃, then putting the mixture into a FL-150 dust removal pulverizer to be pulverized, putting the pulverized mixture into superfine pulverizing equipment to be continuously pulverized to obtain fine powder, wherein the particle size of the coarse pulverized powder is 48 meshes, and the particle size of the fine powder is 100 meshes;
s2: and (3) sterilization: sterilizing the fine powder obtained in S1 by irradiation sterilization60Performing Co-gamma irradiation sterilization with irradiation dose of 6kGy to obtain sterilized fine powder;
s3: packaging: and packaging the fine powder obtained by the S2 treatment by using a polyester/aluminum foil/polyethylene medicinal composite film to obtain the cobra medicinal powder finished product.
The cobra powder obtained in examples 1 to 3 was subjected to powder yield measurement, and the measurement results are shown in Table 2.
TABLE 2 determination of the powder yield
The results show that the powder yield of the fine powder of the cobra can reach more than 90 percent through conventional grinding and superfine grinding after the cobra is dried.
The cobra powder obtained in examples 1 to 3 was subjected to measurement of physicochemical indexes such as water content, total ash content, acid-insoluble ash content, water-soluble extract, and microbial limit, and microbial indexes according to general rules of the four parts of the world in "Chinese pharmacopoeia" 2020, and the measurement results are shown in Table 3.
TABLE 3
For the purpose of sterilization of damp heat60The two methods of Co irradiation sterilization are compared in tests, and the tests are carried out by taking the identification of synthase chain reaction, nitrogen content and microbial limit as indexes. The moist heat sterilization condition refers to traditional Chinese medicine pharmacy, and adopts two modes of sterilization at 121 ℃, 20min and 126 ℃ for 15min,60co irradiation sterilization conditions refer to sanitation department, drug administration [ 1997 ] No. 38, and the specific implementation method formulated by issuing the irradiation traditional Chinese medicine sterilization dose standard specifies the raw material powder of the traditional Chinese medicine, and the irradiation sterilization dose is 6 kGy.
1, using the identification of polymerase chain reaction as an index to investigate different sterilization modes of the cobra, and the result is shown in figure 5.
As shown in FIG. 5, a single DNA band should be amplified near 400bp of the cobra gel electrophoresis, and as a result, after moist heat sterilization, the band is not amplified and may be damaged by cobra powder DNA; but adopt60Co irradiation sterilization is carried out, the dosage is 6kGy, a single DNA strip is amplified near 400bp on the position of the cobra powder corresponding to the gel electrophoresis pattern of the decoction pieces, so the irradiation sterilization method is adopted, and the nitrogen content and the microbial limit before and after sterilization are further investigated.
2. Taking nitrogen content as an index, taking a proper amount of cobra powder before and after sterilization, measuring the nitrogen content according to the first method of the four-part general rule 0704 of the 2020 edition of Chinese pharmacopoeia, and investigating the change of the nitrogen content before and after sterilization, wherein the results are shown in Table 4.
TABLE 4 table of nitrogen content measurement before and after sterilization
The result shows that the raw powder of the product is irradiated by 6kGy of irradiation dose, and the nitrogen content is not obviously changed before and after sterilization.
3. Two batches of cobra powder before and after sterilization in different production places are randomly extracted by taking the measurement result value of the microorganism as an index, the total number of bacterial colonies, escherichia coli, mould, yeast, salmonella and cholate resistant gram negative bacteria are respectively detected according to a traditional Chinese medicine decoction piece microorganism limit inspection method of the four-part general rule 1108 in the 'Chinese pharmacopoeia' 2020 edition, and the results are shown in a table 5.
TABLE 5 post-sterilization microbial test results
The results show that the cobra powder60Co-gamma irradiation sterilization, and the microorganism detection index accords with the microorganism limit standard of non-sterile products in the general rules of the four departments of 2020 edition of Chinese pharmacopoeia for checking the microorganism limit of traditional Chinese medicine decoction pieces.
Combining the above test results, cobra powder is prepared from cobra powder60Co-gamma radiation sterilization method with radiation dose of 6kGy, can be detected by polymerase chain reaction identification, basically has no influence on nitrogen content, and meets the requirement of microbial limit, so that the cobra powder is determined to be adopted60Co-gamma irradiation sterilization method, the irradiation dose is 6 kGy.
And (3) stability test:
in order to examine the stability of the sample, the test refers to the requirement of stability test item in the technical guideline for researching the stability of traditional Chinese medicine and natural medicine, and adopts a long-term stability test method and an accelerated stability test method to examine the stability of three batches of the cobra powder prepared in the example 1-3 under the packaging condition to be on the market, and the three batches of the test product are respectively numbered as G-YJS-20210501-1, Y-YJS-20210501-1 and X-YJS-20210501-1.
(1) Long term stability test method: three batches of cobra powder are placed under the condition of a commercial package (medicinal composite membrane) at 25 +/-2 ℃ and RH60% +/-10% for 2 months, and are examined once in the same month and once in 3 months, wherein the examination lasts for 1 month at present.
(2) Accelerated stability test method: three batches of cobra powder are placed in a commercially available packaging condition (medicinal composite membrane) at 40 +/-2 ℃ and RH75% +/-5% for 2 months, and are examined once in 1 and 2 months respectively for 2 months.
The detection items and results are shown in tables 6-14, and the items such as properties, identification, examination, and microorganism limitation are detected according to the quality standard of cobra powder.
TABLE 6 formulation stability test report (Long term stability)
Note: sample number X-YJS-20210501-1
TABLE 7 formulation stability test report (Long term stability)
Note: sample number G-YJS-20210501-1
TABLE 8 formulation stability test report (Long term stability)
Note: sample number Y-YJS-20210501-1
TABLE 9 formulation stability test report (accelerated stability)
Watch 10
Note: sample number X-YJS-20210501-1
TABLE 11 formulation stability test report (accelerated stability)
TABLE 12
Note: sample number Y-YJS-20210501-1
TABLE 13 formulation stability test report (accelerated stability)
TABLE 14
Note: sample number G-YJS-20210501-1
And (4) conclusion: the cobra powder is placed for 2 months under the conditions of 25 +/-2 ℃ and RH60% +/-10%, and is placed for 2 months under the conditions of 40 +/-2 ℃ and RH75% +/-5% for detection, and all indexes meet the requirements of quality standards, which indicates that the quality of a sample is stable within 2 months.
Mice were subjected to single dose toxicity test of cobra powder by oral drenching:
the test method comprises the following steps: 60 quarantine-qualified SPF-grade ICR mice are selected for the test, half of the mice are male and female, the weight of the mice is 18.4-22.5 g, the mice are bred in cages of 310mm multiplied by 205mm multiplied by 180mm, and 5 mice are bred in each cage. Feeding according to the environmental condition requirements of SPF experimental animals in national standard (GB 14925-2010), and quarantining and environment-adaptive feeding for 3 days.
The test observes the acute toxicity test reaction of ICR mice oral administration cobra powder and cobra decoction piece extractum. 60 ICR mice are selected, and the sex are divided into 3 groups at random according to the body weight, namely a blank control group (0.5 percent of CMC-Na), an cobra powder group (24.0 g of crude drug/kg), and an cobra drink group (52.1 g of crude drug/kg, the administration times of the cobra powder group are kept consistent), and 20 mice are selected in each group. Before the experiment, the animals are fasted for more than 12 hours without water prohibition, then the animals are respectively administrated by oral gavage according to 40mL/kg, the administration is carried out for 2 times (the interval between two administrations is 6 hours) on the same day, the toxic performance and characteristics, the toxic reaction occurrence and recovery time, the death condition and the like of each group of animals are closely and carefully observed and recorded within 0-4 hours after each administration, then the animals are observed for 2 times every day, and the animals are observed once in the morning and afternoon and continuously observed for 14 days. Animals were weighed before and on days 4, 7, 10 and 14 after the day of dosing, respectively, and changes in animal body weight and mortality were recorded.
And (3) test results: effects on general activity status, toxic symptoms and mortality in animals: within 0-4 hours after the oral gavage administration is finished, mice in a blank control group, a cobra powder group and a cobra decoction piece group do not have obvious abnormality in autonomous activity, mental state and dietary conditions, and do not have related toxic reaction and animal death. After administration, mice in the blank control group, the cobra powder group and the cobra decoction piece group are continuously observed for 14 days, and no obvious abnormality, no related toxic reaction and no animal death are observed in the autonomous activity, mental state and diet condition of the mice.
Effect on body weight: animals are weighed before administration on the administration day, on the 4 th day, the 7 th day, the 10 th day and the 14 th day after administration, the weights of the cobra powder group and the cobra decoction piece group have no statistical significance difference compared with the weights of animals of a same-period blank control group, and the weights of the animals are increased within a normal increase range, which indicates that the weight increase of the mice is not obviously influenced by orally pouring the cobra powder and the cobra decoction piece extract into ICR mice.
Gross dissection of ICR mice at the end of the experiment was observed visually: no obvious abnormalities were observed on the surface and section of each organ.
And (4) conclusion: under the test condition, the mice orally administrate the cobra powder, the administration volume is 40mL/kg, 2 times the day, the cumulative dose is 24g crude drug/kg (maximum concentration administration) (2.0-4.5 g orally taken by people, which is equivalent to 400-800 times of the clinical planned dose of 70kg adults), and the animals have no relevant toxic reaction and death; the cobra decoction piece extract is orally administrated by mice, the administration volume is 40mL/kg, 2 times the day, the cumulative dose is 52.1g of crude drug/kg (3-9 g of oral administration is taken by a human, which is equivalent to 400-1301 times of the clinical planned dose of 70kg of adults and is consistent with the administration times of cobra powder), and no related toxic reaction and death of animals are caused.
The rats take cobra powder through oral drenching for 1 month to repeat the administration toxicity test:
the test method comprises the following steps: 100 qualified SD rats with half male and female parts, weight of 180.9-227.1 g and weight of 475 multiplied by 350 multiplied by 200mm are bred in 3 cages, and each cage is provided with 5 rats. Feeding according to the environmental condition requirements of international (GB 14925-2010) SPF-level experimental animals, quarantining the animals and adapting to the environment for 5 days.
The experiment observes the long-term toxic reaction of SD rats which take cobra decoction piece extractum and cobra powder with different doses through oral administration for 1 month (4 weeks) continuously and are stopped taking the medicine for 2 weeks and in the recovery period. SD rats 100 in each half of the sex were divided into 5 groups of 20 animals each based on sex and body weight. The test is divided into blank control group, low, medium and high dosage groups (1.2, 2.3, 4.5g crude drug/kg) of cobra powder and group of cobra tablet (9.8 g crude drug/kg, consistent with administration times of high dosage group of cobra powder). The administration is carried out by gavage according to the volume of 15mL/kg, and the administration is continuously carried out for 1 month. At the end of the dosing period (week 4) and at the end of the recovery period (week 6), 50 rats were dissected according to the schedule, each half male and female. The examination items include: general clinical observations; measuring body weight and food intake; hematology, blood biochemistry, blood coagulation, organ coefficient measurement; and (5) histopathological examination.
And (3) test results:
during the test period, all animals were euthanized as planned, and no animals died.
General clinical observations: during the administration period and the recovery period, the dosage groups of the cobra powder are compared with the blank control group at the same period, and the abnormalities related to drug toxicity do not appear in the appearance signs, behavior activities, secretion and excrement of each cavity and general conditions of animals.
Weight: in the observation period of the administration period and the recovery period, compared with a blank control group in the same period, the cobra powder and the cobra decoction pieces have no obvious influence on the body weight of the rat.
Food intake: during the administration period and the recovery period, compared with the blank control group at the same period, the cobra powder and the cobra drink have no obvious influence on the food intake of rats.
And (3) hematology examination: compared with a blank control group at the same period, the cobra powder and the cobra drink have no obvious influence on the hematology indexes of rats during the administration period and the recovery period.
Biochemical examination of blood: compared with a blank control group at the same period, the cobra powder and the cobra drink have no obvious influence on biochemical indexes of blood of rats during the administration period and the recovery period.
Blood coagulation examination: compared with a blank control group at the same period, the cobra powder and the cobra drink have no obvious influence on the blood coagulation indexes of rats during the administration period and the recovery period.
Organ coefficient: compared with a blank control group at the same period, the cobra powder and the cobra drink have no obvious influence on the index of the organ coefficient of the rat during the administration period and the recovery period.
Gross anatomy and pathology examination: compared with the same-period blank control group, the cobra powder high-dose animals and cobra decoction piece animals dissected at the later administration period and the recovery period have no obvious difference and no pathological changes with toxicological significance.
And (4) conclusion: under the test condition, SD rats orally take cobra powder for 1 month, and no obvious toxic reaction dose (NOAEL) is 4.5g of crude drug/kg (maximum concentration) (2.0-4.5 g is orally taken by people, which is equivalent to 75-150 times of the clinical planned dose of 70kg adults and 11.0-25.0 times of the equivalent dose). The SD rat orally drenches the cobra decoction pieces for 1 month, and the dosage (NOAEL) without obvious toxic reaction is 9.7g of crude drug/kg (3-9 g orally taken by a person, which is equivalent to 75-243 times of the clinical planned dosage of 70kg of adults (the dosage is consistent with the dosage multiple of a cobra powder high-dosage group), and the equivalent dosage is 12.0-36.0 times of the equivalent dosage).
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above-described embodiments. Those skilled in the art should appreciate that many modifications and variations are possible in light of the above teaching without departing from the scope of the invention.
Claims (8)
1. A preparation method of cobra traditional Chinese medicine raw powder is characterized by comprising the following steps:
s1: crushing: oven drying cobra decoction pieces until the water content is below 7%, coarsely pulverizing in a pulverizing device, and further pulverizing in an ultra-fine pulverizing device to obtain fine powder;
s2: and (3) sterilization: sterilizing the fine powder obtained in the step S1 by adopting an irradiation sterilization method to obtain sterilized fine powder;
s3: packaging: packaging the fine powder obtained by the S2 treatment by using a medicinal composite film to obtain the finished product of the cobra medicinal powder.
2. The method for preparing cobra Chinese medicinal raw powder according to claim 1, wherein the drying temperature is 60-70 ℃.
3. The method for preparing raw cobra powder as claimed in claim 1, wherein the pulverizing equipment is FL-150 dust removing pulverizer.
4. The method for preparing cobra Chinese medicinal raw powder according to claim 1, wherein the micronizing equipment is a low temperature micronizer TYM-16L.
5. The method for preparing raw cobra powder as claimed in claim 1, wherein the particle size of the coarse powder is 40-50 mesh.
6. The method for preparing raw traditional Chinese medicine powder for cobras according to claim 1, wherein the particle size of the fine powder is below 120 meshes.
7. The method for preparing cobra Chinese medicinal raw powder according to claim 1, wherein the radiation sterilization method is performed by60Co-gamma irradiation sterilization method, the irradiation dose is 6 kGy.
8. The method for preparing raw cobra powder as claimed in claim 1, wherein the medicinal composite membrane is polyester/aluminum foil/polyethylene.
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