Veterinary ephedra, apricot kernel, gypsum and licorice preparation and preparation method thereof

Abstract

The invention discloses a veterinary ephedra, apricot kernel, gypsum and licorice preparation and a preparation method thereof, and belongs to the technical field of veterinary drug preparation. The preparation method comprises the following steps: preheating the interior of a herbal medicine roaster to 70-90 DEG C, putting bitter apricot kernels into the herbal medicine roaster, and performing heat preservation and stir-frying for 5 + / -1 min; continuously heating to 120-160 DEG C, and frying for 30-40 minutes while keeping the temperature; after stir-frying, putting the hot bitter apricot kernels into an oil press for hot pressing to obtain bitter apricot kernel meal; carrying out crushing treatment and continuous flow cell disruption premixing on bitter almond meal, ephedra and liquorice to obtain homogeneous slurry; carrying out solid-liquid separation on the homogenized slurry to obtain a solid mixture and filtrate, and adding water into the filtrate, the solid mixture loaded into the gauze bag and gypsum for decoction; combining the decoctions, filtering, concentrating, and centrifuging to obtain a supernatant; and treating the supernate and an auxiliary agent to obtain the veterinary ephedra, apricot kernel, gypsum and licorice preparation. The invention provides a preparation method of an ephedra, apricot kernel, gypsum and licorice preparation. The content of amygdalin and hydrocyanic acid can be effectively controlled; the effective active ingredients in the ephedra, the bitter apricot kernel and the liquorice can be safely and efficiently extracted.

Description

Technical Field

[0001] The invention belongs to the technical field of veterinary drug preparation, and particularly relates to a veterinary Maxingshigan preparation and a preparation method thereof. Background Art

[0002] The Maxingshigan preparation is included in the second part of the 2020 edition of the "Chinese Veterinary Pharmacopoeia". The main ingredients are ephedra, bitter almonds, gypsum and licorice. Its main functions are clearing heat, promoting lung function and relieving asthma. It is mainly used to treat lung heat, cough and asthma; it is widely used in the prevention and treatment of respiratory diseases in poultry in clinical practice. Clinical poultry and other animals are often used after inflammatory cough diseases occur. At this time, the poultry has been wheezing and lung deficiency for a long time. The processed Maxingshigan has a good effect of clearing heat, promoting lung function and relieving asthma. Conventional Maxingshigan preparations are to directly grind ephedra, bitter almonds, gypsum and licorice into fine powder, sieve and mix to make powders or press into tablets to make tablets. It has defects such as poor drug absorption and large side effects. Therefore, the current Maxingshigan preparations are mainly liquid preparations and ointments.

[0003] Bitter almonds are one of the main ingredients of the Maxing Shigan preparation, which is mainly used to reduce qi, relieve cough and asthma, and moisten the intestines and relieve constipation. Its main active ingredient is amygdalin. Bitter almonds not only contain amygdalin, but also have enzymes that can decompose amygdalin, which can be activated under certain temperature and humidity. First, amygdalinase hydrolyzes amygdalin to produce cerasin, and then produces amygdalin nitrile under cerasinase, and finally decomposes into benzaldehyde and hydrocyanic acid. Excessive intake or raw consumption can cause hydrocyanic acid poisoning, inhibit cell respiration, and form "intracellular asphyxiation" tissue hypoxia. After oral administration, amygdalin can be decomposed into hydrocyanic acid and benzaldehyde in the body. Hydrocyanic acid can have a certain inhibitory effect on the respiratory center, making respiratory movements tend to be quiet and achieve the effect of antitussive and antiasthmatic. Therefore, if hydrocyanic acid is used in large quantities, it will lead to poisoning, and even respiratory paralysis and death; but at the same time, a small amount of hydrocyanic acid can play the main role of relieving cough and asthma. The main purpose of processing bitter almonds is to kill enzymes and preserve amygdalin. The amygdalin enzyme in processed bitter almonds is destroyed, and amygdalin slowly decomposes to produce an appropriate amount of hydrocyanic acid, which has the effect of relieving cough and relieving asthma. Therefore, how to process bitter almonds is an important factor in controlling the content of amygdalin and hydrocyanic acid in Ma Xing Shi Gan preparations.

[0004] In the preparation process of Ephedra sinica preparations, water extraction (such as decoction) is the safest process. Compared with alcohol extraction and petroleum ether degreasing + ethanol reflux extraction, it does not require the addition of alcohol, ether and other extractants, and thus will not produce organic solvent residues. However, the conventional water extraction method has a low extraction rate for the active ingredients in the medicinal raw materials ephedra, bitter almonds and licorice.

[0005] In view of this, there is an urgent need to provide a method for preparing an ephedra sinica preparation, which can effectively control the content of amygdalin and hydrocyanic acid; and can safely and efficiently extract the effective active ingredients of ephedra, bitter almonds and licorice. Summary of the invention

[0006] In view of the deficiencies and difficulties in the prior art, the present invention aims to provide a veterinary Maxingshigan preparation and a preparation method thereof to solve at least one technical problem in the background technology.

[0007] The present invention is achieved through the following technical solutions:

[0008] The first aspect of the present invention provides a method for preparing a veterinary Maxingshigan preparation, wherein the medicinal raw materials of the veterinary Maxingshigan preparation include: 200 to 400 parts by weight of bitter almonds; 200 to 400 parts by weight of ephedra; 200 to 400 parts by weight of liquorice; 1200 to 1800 parts by weight of gypsum;

[0009] The preparation method comprises the following steps:

[0010] Preheat the stir-frying machine to 70℃~90℃, put the bitter almonds in the stir-frying machine, and stir-fry for 5min±1min;

[0011] Continue heating to 120℃~160℃, keep warm and stir-fry for 30min~40min;

[0012] After frying, the hot bitter almonds are placed in an oil press for hot pressing to remove the oil and obtain bitter almond meal;

[0013] Bitter almond meal, ephedra and liquorice are pulverized and premixed with continuous flow cell disruption to obtain a homogenous slurry;

[0014] The crushed gypsum is packed in a gauze bag; the homogenized slurry is solid-liquid separated into a solid mixture and a filtrate, the solid mixture is packed in a gauze bag, and the filtrate, the solid mixture in the gauze bag and the gypsum are boiled with water, and the boiling is performed at least twice;

[0015] After combining the decoctions, filtering, concentrating and centrifuging to obtain a supernatant;

[0016] The supernatant is treated with an adjuvant to obtain the veterinary Maxingishagan preparation.

[0017] Furthermore, the bitter almond meal, ephedra and liquorice are pulverized and premixed with continuous flow cell disruption to obtain a homogenous slurry, which specifically includes:

[0018] Pre-treat bitter almond meal with microwave at 60℃~80℃ for 4~6min, and then homogenize and crush to obtain bitter almond meal powder;

[0019] Freeze and crush ephedra to obtain ephedra powder;

[0020] Microwave drying of licorice at 60°C to 80°C for 5 to 10 minutes, and then homogenizing and crushing the licorice by mechanical crushing equipment to obtain licorice powder;

[0021] Mixing bitter almond meal powder, ephedra powder and liquorice powder, and dispersing the mixed powder in water by ultrasonication to form a mixed slurry;

[0022] The mixed slurry is processed by a low-temperature and high-pressure continuous flow cell disruptor to obtain a homogenous slurry.

[0023] Furthermore, the working parameters of the low-temperature and high-pressure continuous flow cell disruptor include: the temperature of the low-temperature circulating water bath is 1°C to 5°C, and the pressure of the ultra-high pressure is 50MPa to 150MPa.

[0024] Furthermore, the particle size range of the bitter almond meal powder is 0.2 mm to 0.5 mm; the particle size range of the ephedra powder is 0.1 mm to 0.3 mm; and the particle size range of the licorice powder is 0.2 mm to 0.5 mm.

[0025] Furthermore, the solid mixture is packed in a gauze bag, and the volume of the solid mixture is 1 / 3 to 1 / 2 of the volume of the gauze bag; the crushed gypsum is packed in a gauze bag, and the volume of the gypsum is 1 / 2 to 2 / 3 of the volume of the gauze bag.

[0026] Furthermore, during decoction, water is added in an amount of 5 to 10 times the weight of the raw medicinal materials, and the decoction temperature is 98°C ± 2°C.

[0027] Furthermore, the combined decoction is filtered, concentrated and centrifuged, specifically comprising: combining the decoction, filtering with 100-120 mesh, concentrating to 850-950 parts by weight, and controlling the relative density to be ≥1.06; and centrifuging at a speed of ≥5000r / min to obtain a supernatant.

[0028] Furthermore, the auxiliary agent is a preservative, and the preparation steps of the preservative are:

[0029] Add 0.25% to 0.35% benzoic acid, 0.15% to 0.25% ethyl p-hydroxybenzoate, 0.25% to 0.35% potassium sorbate, and 1.1% to 1.3% ethanol to water, stir evenly, and adjust the pH value to 3.5 to 5.5; control the relative density to be ≥1.05.

[0030] Furthermore, the supernatant is treated with an adjuvant to obtain the veterinary Maxingishen preparation, and the specific operation is as follows:

[0031] The preservative is added with water to a volume of 1000 to 1100 parts by weight to obtain a preservative liquid;

[0032] Slowly add the preservative liquid into the supernatant and continue stirring until it is evenly stirred, then fill and sterilize to obtain the Ma Xing Shi Gan preparation.

[0033] The second aspect of the present invention provides a veterinary Maxingshigan preparation obtained by the above-mentioned preparation method.

[0034] Compared with the prior art, the present invention has the following beneficial effects:

[0035] 1. The present invention provides a method for preparing a maxingshigan preparation, which can effectively control the content of amygdalin and hydrocyanic acid; and can safely and efficiently extract the effective active ingredients in ephedra, bitter almonds and licorice.

[0036] 2. The present invention uses a single-frying, pressing and de-oiling method in the preparation process of the raw medicinal material bitter almond, the purpose of which is to kill enzymes and preserve glycosides. The mass production operation in the GMP workshop is easy to perform. The fried bitter almonds are warm in nature, can remove minor toxins, and are often used to warm and dispel lung cold; at the same time, the inclusion of fatty oil is reduced, and the dissolution rate of the effective ingredients of the medicinal material is better, thereby improving the extraction rate of amygdalin, increasing the utilization of medicinal materials, saving resources, reducing production costs, and improving drug efficacy.

[0037] 3. In the present invention, in the process of preparing Maxing Shigan, a single frying and pressing deoiling method is used to make the oral liquid more clear, the drug stability is better, the precipitation and precipitation of the drug are reduced, the risk of water line blockage caused by farmers is guaranteed, and the efficacy of treating lung deficiency caused by long-term cough caused by cold wind in poultry is improved, thereby playing a good role in sterilization and anti-inflammatory, clearing lung heat, and relieving asthma, improving the sterilization and anti-inflammatory effect, reducing the use of antibiotics, and improving the quality of poultry meat and eggs.

[0038] 4. The present invention grinds the bitter almond meal, ephedra and liquorice and premixes them by continuous flow cell disruption before decoction, which not only retains the activity of the effective ingredients, but also promotes the precipitation of the medicinal ingredients during the subsequent decoction. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 The thin layer chromatograms are of the processed bitter almonds (right), raw bitter almonds (middle), and amygdalin standard (left) in step 1 of Example 1 of the present invention.

[0040] Figure 2 This is a chromatogram of bitter almonds after processing in step 1 of Example 1 of the present invention.

[0041] Figure 3 The chromatogram is of the Maxingshigan preparation prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0042] The present invention will be further described below in conjunction with the accompanying drawings.

[0043] A method for preparing a veterinary Maxingshigan preparation, the medicinal raw materials of the veterinary Maxingshigan preparation comprising: 200 to 400 parts by weight of bitter almonds; 200 to 400 parts by weight of ephedra; 200 to 400 parts by weight of liquorice; 1200 to 1800 parts by weight of gypsum; the component proportions of each medicinal raw material can be adjusted according to actual needs; the following embodiment adopts 300 parts by weight of bitter almonds; 300 parts by weight of ephedra; 300 parts by weight of liquorice; and 1500 parts by weight of gypsum; but is not limited to the listed values, and other values ​​not listed within the numerical range are also applicable.

[0044] The preparation method comprises the following steps S11 to S15:

[0045] S11. Stir-fry, press and remove oil from bitter almonds

[0046] Preheat the inside of the medicine frying machine to 70℃~90℃ for 15min~20min, put the bitter almonds in the medicine frying machine, keep warm and fry for 5min±1min; continue to heat to 120℃~160℃, keep warm and fry for 30min~40min; turn or rotate continuously during the frying process; after frying, place the hot bitter almonds in the oil press for hot pressing, with an oil yield of 36%±4%, and remove the oil to obtain bitter almond meal; collect the bitter almond meal for use, generally use it within one week, to prevent it from being placed for too long, getting damp, losing oil and turning yellow;

[0047] The invention selects complete and sun-dried bitter almonds, whose seed skin is thin and the inside is milky white, and adopts a method of preheating with a slow fire and stir-frying with a medium or high fire to reduce the content of hydrocyanic acid to about 11%. The hot pressing degreasing function is to remove the fatty oil therein, reduce the oil wrapping, increase the precipitation amount of amygdalin during subsequent decocting, enhance the hydrolysis effect of amygdalin, and thus improve the drug efficacy.

[0048] S12. Pretreatment of medicinal materials

[0049] A. Microwave + crushing pretreatment of bitter almonds: microwave pretreatment of bitter almond meal at 60°C to 80°C for 4 to 6 minutes, and then crushing it into bitter almond meal powder with a particle size range of 0.2 mm to 0.5 mm;

[0050] After frying and degreasing, bitter almonds are obtained into granular powdered bitter almond meal, the surface of which will be adhered to some oil; the effects of microwave treatment of bitter almond meal include: first, volatilizing and removing the residual fatty oil adhered to the surface of bitter almond meal, further reducing the wrapping of oil on the bitter almond meal; second, low-temperature microwave treatment can further inactivate the enzyme, making the amygdalin enzyme inactive; third, the mechanical and thermal effects of microwaves can promote the rapid precipitation of amygdalin from cells.

[0051] B. Frozen crushing of ephedra: first, place the ephedra at a temperature below -20°C for more than 30 minutes, and then grind the frozen ephedra into ephedra powder with a degree of D50 = 0.1mm to 0.3mm by a grinder or a pulverizer;

[0052] Ephedra is a herbaceous stem, the main active ingredient of which is ephedrine. Crushing it into powder during decoction is more conducive to the precipitation of ephedrine. However, ephedrine is volatile, and conventional mechanical crushing at room temperature will cause the loss of the effective ingredient ephedrine. The present invention adopts a method of first freezing and then crushing, which effectively retains ephedrine and reduces its volatilization loss.

[0053] C. Microwave + crushing pretreatment of licorice: firstly, the licorice is dried by microwave at 60°C to 80°C for 5min to 10min, and then crushed by mechanical crushing equipment to form licorice powder with a particle size range of 0.2mm to 0.5mm;

[0054] The main active ingredients in licorice are liquiritin and glycyrrhizic acid. Microwaving and then crushing make it easier and faster for liquiritin and glycyrrhizic acid to precipitate during subsequent decoction.

[0055] D. Gypsum: Gypsum is broken up into micron-sized gypsum powder by mechanical crushing or air flow crushing. The reason for crushing the gypsum is that it is conducive to the precipitation of calcium ions and reduces the decoction time.

[0056] E. Premixing bitter almond meal, ephedra and licorice: mixing bitter almond meal powder, ephedra powder and licorice powder, and ultrasonically dispersing the mixed powder in water to form a mixed slurry; treating the mixed slurry with a low-temperature and high-pressure continuous flow cell disruptor to obtain a homogenous slurry;

[0057] The present invention uses low-temperature and high-pressure continuous flow crushing to process a mixed slurry formed by bitter almond meal, ephedra and licorice. In a specific implementation, a low-temperature and high-pressure continuous flow crusher is used as a crushing device, and the mixed slurry is compressed into a homogenizing valve under a high pressure of 50MPa to 150MPa. Due to the compression, extremely high energy is accumulated, and then the mixed slurry is instantly changed from ultra-high pressure to normal pressure when passing through a flow-limiting gap under external force transmission. In this process, high-energy release is generated to cause cavitation explosion, shearing and collision, thereby causing cells of bitter almond meal, ephedra and licorice in the mixed slurry to be crushed, which is more conducive to the precipitation of effective ingredients during decoction; the crushing is carried out in a low-temperature circulating cooling water bath at 1°C to 5°C, which can maintain the activity of the original drug components.

[0058] S13, decoction of medicinal materials

[0059] The crushed gypsum is packed in a gauze bag; the homogenized slurry is solid-liquid separated into a solid mixture and a filtrate, the solid mixture is packed in a gauze bag, and water is added to the filtrate, the solid mixture in the gauze bag and the gypsum and decocted at 98°C±2°C; wherein water is added according to 5 to 10 times the weight of the medicinal material fed, and the decocting is performed at least twice. The decocting time for each time can be adjusted according to actual needs, generally less than 3 hours. In order to save costs and optimize time, 0.5 to 1.5 hours (preferably about 1 hour) is conventionally used, and the decocting is performed twice. The treatment of the medicinal material raw materials of the present invention allows the medicinal active components to be quickly precipitated during decocting, which can reduce a certain amount of decocting time;

[0060] In the specific implementation, the solid mixture is packed in a gauze bag of 100-200 mesh, and the volume of the solid mixture is 1 / 3-1 / 2 of the volume of the gauze bag; the crushed gypsum is packed in a gauze bag of 800-1000 mesh, and the volume of the gypsum is 1 / 2-2 / 3 of the volume of the gauze bag.

[0061] S14, combining the decoctions, filtering through 100-120 mesh, concentrating to 850-950 parts by weight, controlling the relative density to be ≥1.06; and centrifuging at a speed of ≥5000 r / min to obtain a supernatant.

[0062] S15, treating the supernatant with an adjuvant to obtain a veterinary Maxingishan preparation;

[0063] The adjuvant can be any adjuvant allowed in the art, and can be adjusted according to the needs of different dosage forms, such as liquid dosage forms or solid dosage forms. The present invention takes oral liquid as an example, and the adjuvant adopts a preservative, and the preparation steps of the preservative are: add 0.25% to 0.35% benzoic acid, 0.15% to 0.25% ethyl p-hydroxybenzoate, 0.25% to 0.35% potassium sorbate, and 1.1% to 1.3% ethanol to water, stir evenly, and adjust the pH value to 3.5 to 5.5; control the relative density ≥ 1.05; the component ratio of the preservative can be adjusted according to actual needs; the following embodiment adopts 0.3% benzoic acid, 0.2% ethyl p-hydroxybenzoate, 0.3% potassium sorbate, and 1.2% ethanol; but it is not limited to the listed values, and other values ​​not listed in the numerical range are also applicable.

[0064] The specific operation is as follows: add water to the preservative to make the volume to 1000 to 1100 parts by weight to obtain a preservative solution; slowly add the preservative solution to the supernatant and continue stirring until the mixture is uniform, then fill and sterilize to obtain the oral liquid preparation of Maxingshigan. The preservative solution and the supernatant can also be mixed and then centrifuged and spray dried to obtain a dry extract powder or granular preparation.

[0065] In specific implementation, the Maxingshigan preparation prepared by the present invention can be used as a basic preparation, and other functional agents, such as corrosion inhibitors, carriers, and sweeteners, are added to prepare the Maxingshigan preparation with a sustained-release effect and a more suitable taste.

[0066] Example 1

[0067] A method for preparing a veterinary Maxingshigan preparation comprises the following steps:

[0068] Step 1: Prepare bitter almonds

[0069] Weigh 300g of whole and dried bitter almonds, preheat the inside of the medicine frying machine to about 70℃ for about 15min, place the bitter almonds in the medicine frying machine, and fry at 70℃~90℃ for about 5min; continue to heat to 120℃~130℃, and fry at this temperature for about 40min; during the frying process, turn or rotate the bitter almonds continuously, listen to the popping sound, and make the surface yellow to brownish yellow, slightly with burnt spots, and the cross section burnt yellow; when the aroma is emitted, take them out at once; after the frying is completed, place the hot bitter almonds in the oil press while they are still hot, and remove the oil to obtain bitter almond meal;

[0070] Step 2: Pretreatment of medicinal materials

[0071] Pre-treat bitter almond meal with microwave at 70°C for about 5 minutes, and then grind it into bitter almond meal powder with a particle size range of 0.2mm-0.5mm; first keep 300g of ephedra at -35°C for 40 minutes, and then grind the frozen ephedra into ephedra powder with a particle size range of 0.1mm-0.3mm by a grinder or a pulverizer; dry 300g of licorice at 70°C for about 8 minutes, and then homogenize and crush it by mechanical crushing equipment to form licorice powder with a particle size range of 0.2mm-0.5mm; and break up 1500g of gypsum by air flow crushing to form micron-level (1μm-10μm) gypsum powder;

[0072] Bitter almond meal powder, ephedra powder and licorice powder are mixed, and the mixed powder is ultrasonically dispersed in water of twice its weight to form a mixed slurry; the mixed slurry is treated with a low-temperature high-pressure continuous flow cell disruptor to obtain a homogenous slurry; the low-temperature high-pressure continuous flow disruptor is used as a disrupting device, and the mixed slurry is compressed into a homogenizing valve under a high pressure of 50MPa, and extremely high energy is accumulated due to compression. Then, the mixed slurry is instantly changed from ultra-high pressure to normal pressure when passing through a flow-limiting gap under external force transmission. In this process, high energy release is generated to cause cavitation explosion, shearing and collision, thereby causing the bitter almond meal, ephedra and licorice cells in the mixed slurry to be broken to form a homogenous slurry;

[0073] Step 3: Decoction

[0074] The gypsum powder is packed into 800-mesh gauze bags, with each bag filled with 1 / 2 of the volume; the homogeneous slurry prepared in step 2 is separated into a solid mixture and a filtrate by solid-liquid separation, and the solid mixture is packed into 200-mesh gauze bags, with each bag filled with 1 / 2 of the volume; water is added to the filtrate, the solid mixture packed in the gauze bag and the gypsum at 98°C±2°C and boiled; water is added according to 8 times the weight of the medicinal materials fed, and the decoction is performed twice, and the decoction time each time is 1 hour.

[0075] Step 4: Combine the decoctions, filter through 100-120 mesh, concentrate to about 900 g, and control the relative density to be ≥1.06; centrifuge at a speed of ≥5000 r / min to obtain a supernatant.

[0076] Step 5. Add 0.3% benzoic acid, 0.2% ethyl p-hydroxybenzoate, 0.3% potassium sorbate, and 1.2% ethanol (concentration ≥ 95%) into water, stir evenly, and adjust the pH value to 4.5; control the relative density to be ≥ 1.05; add water to the preservative to make the volume to 1050g to obtain a preservative solution; slowly add the preservative solution to the supernatant and continue stirring until it is evenly stirred, then fill and sterilize to obtain the Ma Xing Shi Gan preparation.

[0077] Example 2

[0078] This Example 2 prepares a veterinary Maxingshigan preparation based on Example 1. The only difference between this Example 2 and Example 1 is the frying temperature in step 1. The other steps and reaction conditions are the same as those in Example 1.

[0079] Step 1 of Example 2 is as follows: weigh 300 g of whole and dry bitter almonds, preheat the inside of the roasting machine to about 70°C for about 15 minutes, place the bitter almonds in the roasting machine, and roast at 70°C-90°C for about 5 minutes; continue heating to 135°C-145°C, and roast for about 40 minutes; during the roasting process, turn or rotate the almonds continuously to hear the popping sound, so that the surface is yellow to brownish yellow with slight burnt spots and the cross section is burnt yellow; when the aroma is emitted, take them out at once; after the roasting is completed, place the hot bitter almonds in an oil press while they are still hot to remove the oil to obtain bitter almond meal.

[0080] Example 3

[0081] This Example 3 prepares a veterinary Maxingshigan preparation based on Example 1. The only difference between this Example 3 and Example 1 is the frying temperature in step 1. The other steps and reaction conditions are the same as those in Example 1.

[0082] Step 1 of Example 3 is as follows: weigh 300 g of whole and dry bitter almonds, preheat the inside of the roasting machine to about 70°C for about 15 minutes, place the bitter almonds in the roasting machine, and stir-fry at 70°C-90°C for about 5 minutes; continue heating to 150°C-160°C, and stir-fry for about 40 minutes; during the frying process, turn or rotate the almonds continuously to hear the popping sound, so that the surface is yellow to brownish yellow with slight burnt spots and the cross section is burnt yellow; when the aroma is emitted, take them out at once; after the frying is completed, place the hot bitter almonds in an oil press while they are still hot to remove the oil to obtain bitter almond meal.

[0083] Example 4

[0084] This Example 4 prepares a veterinary Maxingshigan preparation based on Example 1. The only difference between this Example 4 and Example 1 is the temperature during microwave treatment of bitter almond meal and licorice in step 2. The other steps and reaction conditions are the same as those in Example 1.

[0085] In step 2 of this embodiment 4, the bitter almond meal and liquorice are specifically processed as follows:

[0086] The bitter almond meal was pretreated with microwave at 60°C for about 5 minutes, and then crushed into bitter almond meal powder with a particle size range of 0.2mm-0.5mm; 300g of licorice was dried at 60°C for about 8 minutes in microwave, and then homogenized and crushed by mechanical crushing equipment to form licorice powder with a particle size range of 0.2mm-0.5mm.

[0087] Example 5

[0088] This Example 5 prepares a veterinary Maxingshigan preparation based on Example 1. The only difference between this Example 5 and Example 1 is the temperature during microwave treatment of bitter almond meal and licorice in step 2. The other steps and reaction conditions are the same as those in Example 1.

[0089] In step 2 of this embodiment 5, the bitter almond meal and liquorice are specifically processed as follows:

[0090] The bitter almond meal was pretreated with microwaves at 80° C. for about 5 minutes, and then crushed into bitter almond meal powder with a particle size range of 0.2 mm to 0.5 mm; 300 g of licorice was dried at 80° C. for about 8 minutes, and then homogenized and crushed by a mechanical crushing equipment to form licorice powder with a particle size range of 0.2 mm to 0.5 mm.

[0091] Example 6

[0092] This Example 6 prepares the veterinary Maxigol preparation based on Example 1. The only difference between this Example 6 and Example 1 is the pressure of the low-temperature and high-pressure continuous flow cell disruptor in step 2. The other steps and reaction conditions are the same as those in Example 1.

[0093] In this embodiment, the high pressure of the low-temperature high-pressure continuous flow cell disruptor is set to 100 MPa during premixing.

[0094] Example 7

[0095] This Example 7 prepares the veterinary Maxigol preparation based on Example 1. The only difference between this Example 7 and Example 1 is the pressure of the low-temperature and high-pressure continuous flow cell disruptor in step 2. The other steps and reaction conditions are the same as those in Example 1.

[0096] In this embodiment, the high pressure during premixing of the low temperature and high pressure continuous flow cell disruptor is set to 150 MPa.

[0097] Comparative Example 1

[0098] This comparative study was conducted to investigate the effects of different methods of processing bitter almonds on the contents of amygdalin and hydrocyanic acid.

[0099] Sample 1: raw bitter almonds;

[0100] Sample 2: stir-fry bitter almonds over low heat; the specific steps are: preheat the stir-frying machine to 70°C for 15 minutes, place the bitter almonds in the stir-frying machine, and stir-fry over low heat at 70°C to 90°C for about 45 minutes;

[0101] Sample 3: Stir-fry bitter almonds on medium-high heat; preheat the stir-fry machine to 120℃~130℃ for 15 minutes, place the bitter almonds in the stir-fry machine, and stir-fry at this temperature for about 45 minutes;

[0102] Sample 4: Pre-fry over low heat + fry over medium-high heat; weigh 300g of whole and dry bitter almonds, preheat the inside of the frying machine to about 70℃ for 15min, place the bitter almonds in the frying machine, and fry at 70℃~90℃ for about 5min; continue heating to 120℃~130℃, and fry at this temperature for about 40min;

[0103] Sample 5: bitter almond meal obtained after treatment in step 1 of Example 1;

[0104] Sample 6: bitter almond meal obtained after the treatment in step 1 of Example 2;

[0105] Sample 7: Bitter almond meal obtained after treatment in step 1 of Example 3.

[0106] Samples 1 to 7 were ground into powders, and the contents of hydrocyanic acid and amygdalin therein were determined. The specific results are shown in Table 1.

[0107] The content of amygdalin was determined by high performance liquid chromatography. Specifically, octadecylsilane bonded silica gel was used as a filler; acetonitrile-0.1% phosphoric acid solution (8:92) was used as a mobile phase; the detection wavelength was 207nm, and the number of theoretical plates calculated based on the amygdalin peak should be no less than 7000; an appropriate amount of amygdalin reference substance was taken, accurately weighed, and methanol was added to make a 40μg / mL solution to obtain an amygdalin reference substance solution, which was injected into a liquid chromatograph to measure and draw a standard curve; approximately 0.25g of powder (passed through a No. 2 sieve) of each sample 1 to sample 7 was taken, accurately weighed, and placed in a stoppered conical flask , accurately add 25mL of methanol, seal, weigh, ultrasonically treat (power 250W, frequency 50kHz) for 30 minutes, let cool, weigh again, make up the lost weight with methanol, shake well, filter, accurately measure 5ml of the filtrate, put it in a 50ml volumetric flask, add 50% methanol to dilute to the scale, shake well, filter, take the filtrate to obtain the sample solution to be tested; accurately aspirate 10μL~20μL of the sample solution to be tested, inject it into liquid chromatograph, measure, and calculate the concentration of amygdalin according to the linear relationship corresponding to the standard curve.

[0108] Determination of hydrocyanic acid content by ion chromatography. Specifically including: using Thermo Fisher AS11 analytical column (4mm×250mm) and AG11 protective column (4mm×50mm), the mobile phase is 0.05mol / L NaOH solution; the flow rate is 0.8mL / min, the column temperature is 30℃±5℃, the detector is a pulsed amperometric detector, the working electrode is a silver electrode, the reference electrode is Ag / AgCl, the detection potential is a three-potential, and the injection volume is 25μL; take an appropriate amount of cyanide component analysis standard solution in water, accurately weigh it, add 2% NaOH to make a series of reference solutions of 0.01μg / mL to 20μg / mL, that is, the reference solution is obtained, the reference solution is injected into the chromatograph, and the standard curve is measured and drawn; take about 10g of sample 1 to sample 7 powder (passed through No. 2 sieve) respectively, accurately weigh it, add water and place it in a 1000mL distillation bottle, add water to make the sample completely immersed, and then add 5mL 10% tartaric acid solution, the distillation flask is externally connected to a steam generator and a condenser, the distillate generated by heating is introduced into a volumetric flask (with 30 mL of a built-in 0.2% NaOH solution as an absorption liquid) through the condenser, and the distillation is stopped when the distillate volume is about 250 mL, water is added to make up the volume, and the sample solution to be tested is obtained; the sample solution to be tested is accurately aspirated respectively, and the sample is injected according to the chromatographic conditions, and the concentration of hydrocyanic acid is calculated according to the linear relationship corresponding to the standard curve.

[0109] Table 1

[0110] Hydrocyanic acid content / % Amygdalin content / % Sample 1 0.1401 4.353 Sample 2 0.1237 3.216 Sample 3 0.1039 3.639 Sample 4 0.0689 4.066 Sample 5 0.0165 4.008 Sample 6 0.0153 3.956 Sample 7 0.0148 3.918

[0111] Hydrocyanic acid / amygdalin content = C 测 *V / M, where C 测(mg / mL) refers to the measured concentration of hydrocyanic acid / amygdalin, V (mL) refers to the volume of the hydrocyanic acid / amygdalin sample solution to be tested, and M (mg) refers to the mass of raw bitter almonds.

[0112] From the data in Table 1, it can be seen that the content of amygdalin in the raw bitter almonds of Sample 1 is the highest, and the content of amygdalin is lost to varying degrees after processing; similarly, the content of hydrocyanic acid is also the highest, indicating that the enzyme in the bitter almonds is not destroyed, and the enzyme is activated after the bitter almonds are heated, thereby decomposing amygdalin and producing a large amount of hydrocyanic acid.

[0113] Sample 2 and Sample 3 were prepared with low heat and medium-high heat respectively for bitter almonds. As can be seen from the data in Table 1, the glycoside preservation effect was poor and the effect of enzyme destruction was limited, resulting in a significant decrease in the content of amygdalin and only a slight decrease in hydrocyanic acid. However, the effect of Sample 3 was greater than that of Sample 2.

[0114] Sample 4 uses the method of pre-frying bitter almonds on low heat first and then frying them on medium-high heat. From the data in Table 1, it can be seen that its glycoside-preserving and enzyme-removing effects are higher than those of the single frying method, especially the content of hydrocyanic acid is reduced by more than 50%.

[0115] Sample 5 is the bitter almond meal obtained in Example 1 of the present invention. It is subjected to hot pressing and de-oiling treatment on the basis of Sample 4. As can be seen from the data in Table 1, the content of amygdalin is not much different from that of Sample 4, with a decrease of less than 0.06%, while the content of hydrocyanic acid is significantly reduced; the reason is that: the fatty oil of bitter almonds contains almost no amygdalin, so the loss of amygdalin after de-oiling treatment is almost negligible; however, bitter almond oil promotes the enzymatic hydrolysis of amygdalin, so the content of hydrocyanic acid is further reduced after de-oiling treatment.

[0116] Sample 6 and Sample 7 are the bitter almond meal prepared in Example 2 and Example 3 respectively. The frying temperature was increased over medium to high heat during the processing. It can be seen from the data in Table 1 that as the frying temperature increased, the content of hydrocyanic acid decreased to a certain extent, but the content of amygdalin also decreased, but basically more than 90% of the glycosides were retained.

[0117] Amygdalin was identified by thin layer chromatography. The thin layer chromatograms of the processed bitter almonds (right), raw bitter almonds (middle), and standard amygdalin (left) in step 1 of Example 1 of the present invention are as follows: Figure 1 As shown, the chromatograms of the bitter almond and the maxingshigan preparation after processing in step 1 of Example 1 of the present invention are respectively as shown in Figure 2 and Figure 3 As shown by Figures 1 to 3 It can be seen that the single-frying and oil-removing processed bitter almonds of the present invention have excellent glycoside preservation effect and high extraction rate.

[0118] Comparative Example 2

[0119] Compared with Example 1, in Comparative Example 2, the operation of continuous flow cell disruption premixing in step 2 is deleted in the pretreatment of medicinal material raw materials, and the other steps and reaction conditions are consistent with those of Example 1.

[0120] The specific steps 2 and 3 of this comparative example 2 are as follows:

[0121] Step 2: Pretreatment of medicinal materials

[0122] Pre-treat bitter almond meal with microwave at 70°C for about 5 minutes, and then grind it into bitter almond meal powder with a particle size range of 0.2mm-0.5mm; first keep 300g of ephedra at -35°C for 40 minutes, and then grind the frozen ephedra into ephedra powder with a particle size range of 0.1mm-0.3mm by a grinder or a pulverizer; dry 300g of licorice at 70°C for about 8 minutes, and then homogenize and crush it by mechanical crushing equipment to form licorice powder with a particle size range of 0.2mm-0.5mm; and break up 1500g of gypsum by air flow crushing to form micron-level (1μm-10μm) gypsum powder;

[0123] Step 3: Decoction

[0124] Wrap the gypsum powder in 800-mesh gauze bags, with each bag filled with 1 / 2 of the volume; wrap the ephedra powder, bitter almond meal, and licorice powder obtained in step 2 in 200-mesh gauze bags, with each bag filled with 1 / 2 of the volume, add water at 98°C±2°C and boil; add water 8 times the weight of the raw materials, boil twice, and each boiling time is 1 hour.

[0125] Comparative Example 3

[0126] Compared with Example 1, in the pretreatment of the medicinal raw materials, conventional steps were used for crushing bitter almond meal, ephedra, and licorice, and the other steps and reaction conditions were consistent with those of Example 1.

[0127] Step 2 of this comparative example 3 is specifically as follows:

[0128] The ephedra, licorice and the bitter almond meal prepared in step 1 are ground into ephedra powder, licorice powder and bitter almond meal powder with corresponding particle size ranges by a grinder or a pulverizer; the bitter almond meal powder, the ephedra powder and the licorice powder are mixed, and the mixed powder is ultrasonically dispersed in 2 times the weight of water to form a mixed slurry; the mixed slurry is treated with a low-temperature and high-pressure continuous flow cell disruptor to obtain a homogeneous slurry.

[0129] Comparative Example 4

[0130] Compared with Example 1, in Comparative Example 4, the raw bitter almond medicinal material is used without processing in Step 2, that is, Step 1 is deleted, and the other steps and reaction conditions are the same as those in Example 1.

[0131] Comparative Example 5

[0132] Compared with Example 1, the bitter almond medicinal material in step 2 of this comparative example 5 adopts sample 2 in comparative example 1, i.e., bitter almonds cooked over low heat, and the other steps and reaction conditions are the same as those in Example 1.

[0133] Comparative Example 6

[0134] Compared with Example 1, the bitter almond medicinal material in step 2 of this comparative example 6 adopts sample 3 in comparative example 1, that is, bitter almonds processed only with medium to high heat, and the other steps and reaction conditions are the same as those in Example 1.

[0135] Comparative Example 7

[0136] Compared with Example 1, the bitter almond medicinal material in step 2 of this comparative example 7 adopts sample 4 in comparative example 1, that is, bitter almonds that are pre-fried over low heat + fried over medium-high heat and not hot-pressed, and the other steps and reaction conditions are the same as those in Example 1.

[0137] Comparative Example 8

[0138] In this comparative example, conventional decoction was used to prepare the Maxingshigan preparation. Specifically, 300 g of ephedra, 1500 g of gypsum, 300 g of bitter almonds, and 300 g of licorice were crushed into particles and directly added. The particles were decocted twice, each time for 1 hour. The decoctions were combined, allowed to stand, filtered, and centrifuged to obtain the supernatant. The same auxiliary agents as in Example 1 were added to obtain the Maxingshigan preparation.

[0139] The contents of the active ingredients of the Maxingshigan preparations prepared in Examples 1 to 7 and Comparative Examples 2 to 8 were measured by liquid chromatography, compared with the contents in the medicinal raw materials, and the extraction rates of the active ingredients were calculated. The results are shown in Table 2.

[0140] Table 2

[0141] Amygdalin extraction rate / % Ephedrine extraction rate / % Glycyrrhizic acid extraction rate / % Example 1 79.51 71.86 73.65 Example 2 80.29 71.82 73.62 Example 3 80.01 71.86 73.64 Example 4 78.53 71.85 72.87 Example 5 80.33 71.85 74.69 Example 6 81.19 73.54 75.22 Example 7 81.91 74.11 76.07 Comparative Example 2 72.04 61.49 66.98 Comparative Example 3 71.66 60.36 68.42 Comparative Example 4 58.81 71.83 73.62 Comparative Example 5 62.65 71.85 73.64 Comparative Example 6 64.67 71.86 73.65 Comparative Example 7 67.55 71.84 73.64 Comparative Example 8 21.55 18.24 34.15

[0142] From the comparison of Examples 1 to 7 in Table 2, it can be seen that the bitter almond processing method and the medicinal material pretreatment method of the present invention can greatly increase the medicinal ingredients in bitter almond, ephedra and licorice.

[0143] From the comparison of Example 1 to Example 3 in Table 2, it can be seen that as the frying temperature of bitter almonds increases, the extraction rate of amygdalin increases, but when the temperature increases to a certain value, the increase in the extraction rate is not obvious.

[0144] From the comparison of Example 1, Example 4 to Example 5 in Table 2, it can be seen that with the increase of the microwave treatment temperature of bitter almonds and licorice, the extraction rates of amygdalin and glycyrrhizic acid increase. In order to avoid the precipitation of other impurities in bitter almonds and licorice, the temperature is controlled at 60°C to 80°C.

[0145] From the comparison of Example 1 and Example 6 to Example 7 in Table 2, it can be seen that with the increase of high pressure during low-temperature and high-pressure continuous flow crushing, the extraction rates of amygdalin, glycyrrhizic acid and ephedrine increase. However, if the pressure is continuously increased, it will lead to excessive cell crushing and aggravate the precipitation of impurities, so the pressure is set to 50MPa~150MPa.

[0146] From the comparison between Example 1 and Comparative Example 2 in Table 2, it can be seen that when the medicinal raw materials are not subjected to low-temperature and high-pressure continuous flow crushing and premixing, the extraction rates of amygdalin, glycyrrhizic acid and ephedrine are all reduced.

[0147] From the comparison of Example 1 and Comparative Example 3 in Table 2, it can be seen that when the medicinal raw materials are crushed by conventional means, the extraction rates of amygdalin, glycyrrhizic acid and ephedrine all decrease, among which the decrease in ephedrine is the most obvious.

[0148] From the comparison of Example 1 and Comparative Examples 4 to 7 in Table 2, it can be seen that when the bitter almonds are not processed or conventionally fried, the amygdalin extraction rate is significantly lower than that of Example 1 of the present invention. Among them, although the amygdalin content of the bitter almonds in Comparative Example 7 is not much different from that in Example 1, during decoction, the oil will promote the enzymatic hydrolysis of amygdalin, resulting in a decrease in its content.

[0149] Comparative Example 8 adopts conventional decoction method to prepare the Maxingshigan preparation. It can be seen from the data in Table 2 that the extraction rate of effective active ingredients in the medicinal materials is very low.

[0150] The above only expresses the preferred embodiments of the present invention, and the description is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that for ordinary technicians in this field, several modifications, improvements and substitutions can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be based on the attached claims.

Claims

1. A method for preparing a veterinary Maxingshigan preparation, characterized in that: The medicinal raw materials of the veterinary Maxingshigan preparation include: 200 to 400 parts by weight of bitter almonds; 200 to 400 parts by weight of ephedra; 200 to 400 parts by weight of liquorice; 1200 to 1800 parts by weight of gypsum; The preparation method comprises the following steps: Preheat the stir-frying machine to 70℃~90℃, put the bitter almonds in the stir-frying machine, and stir-fry for 5min±1min; Continue heating to 120℃~160℃, keep warm and stir-fry for 30min~40min; After frying, the hot bitter almonds are placed in an oil press for hot pressing to remove the oil and obtain bitter almond meal; Bitter almond meal, ephedra and liquorice are pulverized and premixed with continuous flow cell disruption to obtain a homogenous slurry; The crushed gypsum is packed in a gauze bag; the homogenized slurry is solid-liquid separated into a solid mixture and a filtrate, the solid mixture is packed in a gauze bag, and water is added to the filtrate, the solid mixture in the gauze bag and the gypsum for decoction at least twice; After combining the decoctions, filtering, concentrating and centrifuging to obtain a supernatant; The supernatant is treated with an adjuvant to obtain the veterinary Maxingishagan preparation.

2. The method for preparing the veterinary Maxingshigan preparation according to claim 1, characterized in that: The bitter almond meal, ephedra and liquorice are pulverized and premixed with continuous flow cell disruption to obtain a homogenous slurry, and the specific operation is as follows: Pre-treat bitter almond meal with microwave at 60℃~80℃ for 4min~6min, and then homogenize and crush to obtain bitter almond meal powder; Freeze and crush ephedra to obtain ephedra powder; Microwave drying of licorice at 60°C to 80°C for 5 to 10 minutes, and then homogenizing and crushing the licorice by mechanical crushing equipment to obtain licorice powder; Mixing bitter almond meal powder, ephedra powder and liquorice powder, and dispersing the mixed powder in water by ultrasonication to form a mixed slurry; The mixed slurry is processed by a low-temperature and high-pressure continuous flow cell disruptor to obtain a homogenous slurry.

3. The method for preparing the veterinary Maxingshigan preparation according to claim 2, characterized in that: The working parameters of the low-temperature and high-pressure continuous flow cell disruptor include: the temperature of the low-temperature circulating water bath is 1° C. to 5° C., and the pressure of the ultrahigh pressure is 50 MPa to 150 MPa.

4. The method for preparing the veterinary Maxingshigan preparation according to claim 2, characterized in that: The particle size range of the bitter almond meal powder is 0.2 mm to 0.5 mm; the particle size range of the ephedra powder is 0.1 mm to 0.3 mm; and the particle size range of the liquorice powder is 0.2 mm to 0.5 mm.

5. The method for preparing the veterinary Maxingshigan preparation according to claim 1, characterized in that: The solid mixture is packed in a gauze bag, and the volume of the solid mixture is 1 / 3 to 1 / 2 of the volume of the gauze bag; the crushed gypsum is packed in a gauze bag, and the volume of the gypsum is 1 / 2 to 2 / 3 of the volume of the gauze bag.

6. The method for preparing the veterinary Maxingshigan preparation according to claim 1, characterized in that: When decocting, add water according to 5 to 10 times the weight of the raw medicinal materials, and the decoction temperature is 98℃±2℃.

7. The method for preparing the veterinary Maxingshigan preparation according to claim 1, characterized in that: The combined decoction is filtered, concentrated and centrifuged, specifically comprising: combining the decoction, filtering with 100-120 mesh, concentrating to 850-950 parts by weight, and controlling the relative density to be ≥1.06; and centrifuging at a speed of ≥5000r / min to obtain a supernatant.

8. The method for preparing the veterinary Maxingshigan preparation according to claim 1, characterized in that: The auxiliary agent is a preservative, and the preparation steps of the preservative are: Add 0.25% to 0.35% benzoic acid, 0.15% to 0.25% ethyl p-hydroxybenzoate, 0.25% to 0.35% potassium sorbate, and 1.1% to 1.3% ethanol to water, stir evenly, and adjust the pH value to 3.5 to 5.5; control the relative density to be ≥1.

05.

9. The method for preparing the veterinary Maxingshigan preparation according to claim 8, characterized in that: The supernatant is treated with an adjuvant to obtain the veterinary Maxingishen preparation, and the specific operation is as follows: The preservative is added with water to a volume of 1000 to 1100 parts by weight to obtain a preservative liquid; Slowly add the preservative liquid into the supernatant and continue stirring until it is evenly stirred, then fill and sterilize to obtain the Ma Xing Shi Gan preparation.

10. A veterinary Maxingshigan preparation prepared by the preparation method according to any one of claims 1 to 9.

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