CN111388573A - Medicine containing doxycycline hydrochloride for treating metritis of animals and preparation method - Google Patents

Abstract

The invention belongs to the technical field of veterinary medicines, and discloses a medicine containing doxycycline hydrochloride for treating metritis of animals and a preparation method thereof, wherein the medicine containing doxycycline hydrochloride for treating metritis of animals comprises 3.2kg of doxycycline hydrochloride, 0.8kg of lactic acid TMP0, 2kg of houttuynia cordata extract, 0.8kg of Chinese angelica extract, 2kg of patrinia extract, 2kg of astragalus polysaccharide, 1.6kg of scutellaria baicalensis extract, 12kg of tartaric acid, 2.4kg of sodium dodecyl sulfate, 10kg of lactose, 16kg of corn starch, 4kg of absolute ethyl alcohol, 24.15kg of sodium bicarbonate mixture, 1.020kg of magnesium stearate mixture and 2.4kg of carboxymethyl starch sodium by mass. The traditional Chinese medicine composition provided by the invention has a good effect of treating the metritis of large animals such as pigs, cattle and donkeys, has a lasting effect, and does not rebound after being cured once. The prescription of the invention does not expand the bag, and the tablet does not stick to the punch.

Description

Medicine containing doxycycline hydrochloride for treating metritis of animals and preparation method

Technical Field

The invention belongs to the technical field of veterinary medicines, and particularly relates to a medicine containing doxycycline hydrochloride for treating metritis of animals and a preparation method thereof.

Background

At present, the metritis of cattle, pigs and other livestock such as donkey is mainly the inflammation of endometrium, so the endometritis is also called endometritis. Myometritis, serositis, may occur only in postpartum acute metritis, but rarely. Common endometritis of cattle, usually inflammation of uterine mucosa or suppurative inflammation, is one of the most common reproductive organ diseases after delivery and abortion. Metritis is a common disease of dairy cows after being infected with pathogenic bacteria secondarily or by mating infection when the birth is difficult, the uterus is prolapsed and the placenta is not descended, and in recent years, with the increase of the yield of the dairy cows, the cattle herd is enlarged, and the incidence rate of the metritis is up to 25 percent. Due to the influence of the inflammatory process, inflammatory products and bacterial toxins of uterine mucous membranes, on one hand, cattle have sexual cycle disorder, and on the other hand, the sexual cycle disorder directly harms the sperm motility and embryo implantation, so that breeding infertility is caused, and the cow infertility is one of the important reasons for cow infertility.

Infection by pathogenic microorganisms is a major cause of metritis. The pathogenesis is caused by poor delivery room sanitation or delivery on a stable bed polluted by excrement and urine, the vulva and the tail root of a parturient cow pollute the excrement without thorough cleaning and disinfection, the arms and instruments of a patient are not disinfected tightly when the parturient is in delivery or the placenta is stripped, the placenta is not putrefy and decomposed, lochia is stagnated, a delivery channel is damaged, and the disinfection is not tight when artificial insemination or vaginal examination is carried out, so that pathogenic bacteria invade into the uterus. The pathogenic bacteria causing the metritis are usually easily seen and mainly comprise streptococcus, escherichia coli, staphylococcus and the like. By bacteriological examination of cows with metritis, 75.56% of the three bacteria were isolated. The detection rate of streptococcus is 48.89%, that of colibacillus is 26.7%, that of staphylococcus is 13.3%, and that of proteus, corynebacterium and other bacteria is the next step.

Metritis is one of common diseases of dairy cows, serious people can be adhered to surrounding tissues, or factor cervical orifice is closed to cause secondary uterine apocenosis, so that oestrus cycle is disordered and sterility is frequently matched, and the conception rate and the dairy production of the dairy cows are directly influenced. For a long time, people commonly use common medicaments such as potassium permanganate, rivanol, iodine solution, terramycin, penicillin, erythromycin and the like to carry out traditional treatment, and the effect is not ideal. Metritis is a common reproductive organ disease of dairy cows, so that the reproductive capacity of the sick dairy cows is reduced, the milk yield is reduced, the farrowing interval is prolonged, and some dairy cows are forced to be eliminated due to repeated mating infertility, so that the dairy cow breeding industry suffers from huge economic loss, and the breeding and economic benefit of the dairy cows are seriously influenced. Although a great deal of manpower and material resources are put into various places for prevention and treatment, the morbidity is still increased or not reduced, especially the long-term use of a great deal of antibiotics and disinfectants leads to the enhancement of the drug resistance of pathogenic bacteria, and because the uterus volume recovery is influenced by a plurality of times of excessive washing, the satisfactory treatment effect is often not obtained clinically.

Through the above analysis, the problems and defects of the prior art are as follows: (1) the medicament containing doxycycline hydrochloride for treating animal metritis provided by the prior art has the advantages of poor treatment effect, short action duration and easy relapse in healing effect. In addition, the boiling tablet provided by the prior art is easy to expand and adhere.

The difficulty in solving the above problems and defects is: the single use of western medicine can not ensure the lasting curative effect, or the formula is unreasonable, or the administration mode is not right.

The significance of solving the problems and the defects is as follows: can be produced in batch, and has improved curative effect and product quality. Preventing recurrence.

Disclosure of Invention

In order to solve the problems in the prior art, the invention provides a medicament containing doxycycline hydrochloride for treating metritis of animals and a preparation method thereof.

The medicine containing doxycycline hydrochloride for treating metritis of animals comprises 2.4-4 kg of doxycycline hydrochloride, 0.6-1.0 kg of lactic acid TMP, 1.5-2.5 kg of houttuynia cordata extract, 0.6-1.0 kg of angelica sinensis extract, 1.5-2.5 kg of patrinia extract, 1.5-2.5 kg of astragalus polysaccharide, 1.2-2.0 kg of scutellaria baicalensis extract, 10-14 kg of tartaric acid, 1.2-2.4 kg of sodium dodecyl sulfate, 8-12 kg of lactose, 12-20 kg of corn starch, 4kg of absolute ethyl alcohol, 20-30 kg of sodium bicarbonate mixture, 0.8-1.2 kg of magnesium stearate mixture and 2.4kg of carboxymethyl starch sodium by mass.

Further, the medicine containing doxycycline hydrochloride for treating metritis of animals comprises 3.2kg of doxycycline hydrochloride, 0.8kg of lactic acid TMP0.8kg, 2kg of houttuynia cordata extract, 0.8kg of Chinese angelica extract, 2kg of patrinia extract, 2kg of astragalus polysaccharide, 1.6kg of scutellaria baicalensis extract, 12kg of tartaric acid, 2.4kg of sodium dodecyl sulfate, 10kg of lactose, 16kg of corn starch, 4kg of absolute ethyl alcohol, 24.15kg of sodium bicarbonate mixture, 1.020kg of magnesium stearate mixture and 2.4kg of carboxymethyl starch sodium by mass.

3.2kg of doxycycline hydrochloride, 0.8kg of lactic acid TMP0.8kg, 2kg of houttuynia cordata extract and 0.8kg of Chinese angelica extract, (some Chinese medicines for promoting blood circulation, removing blood stasis and clearing heat and toxic materials can achieve the same effect). Herba Patriniae extract 2kg, radix astragali polysaccharide 2kg, Scutellariae radix extract 1.6kg, tartaric acid 12kg, sodium dodecyl sulfate 2.4kg, lactose 10kg and corn starch 16kg, mixing for 30min, granulating with 60% ethanol of 14 mesh.

Further, the anhydrous ethanol is used for preparing 60% ethanol.

Further, the sodium bicarbonate mixture consists of 20kg of sodium bicarbonate, 2kg of motherwort herb extract, 2kg of ligusticum wallichii extract, 2kg of absolute ethyl alcohol and PVPK300.15kg (preparation of a binder); the above components except for the adhesive are mixed for 30min and independently granulated into 14 meshes.

Further, the K30 is dissolved in 75% ethanol, and the 75% ethanol is prepared from absolute ethanol;

the magnesium stearate mixture consists of 0.9kg of magnesium stearate and 120g of borneol, and the borneol and the magnesium stearate are crushed together, dried and then added externally.

The invention also aims to provide a preparation method of a medicament containing doxycycline hydrochloride for treating metritis of animals, which comprises the following steps:

step one, drying the granulated acid-base granules in an oven at the temperature of 60-65 ℃ for 3-5 h. Controlling the moisture of the granules to be 3-4%, and finishing the granules with 12 meshes;

and step two, adding the acid-base granules together with the additional auxiliary materials of magnesium stearate, borneol and carboxymethyl starch sodium, mixing for 30min by using a two-dimensional mixer, and tabletting after the semi-finished product is qualified.

Further, the prepared tablets were: 20 g/tablet.

The invention also provides a medicament for treating the metritis of the pigs, which is prepared from the medicament containing doxycycline hydrochloride for treating the metritis of animals.

The invention also provides a medicament for treating the metritis of the cattle, which is prepared from the medicament containing doxycycline hydrochloride for treating the metritis of the animals.

The invention also provides a medicament for treating metritis of animals, which is prepared from the medicament containing doxycycline hydrochloride.

By combining all the technical schemes, the invention has the advantages and positive effects that: the traditional Chinese medicine composition provided by the invention has a good effect of treating the metritis of large animals such as pigs, cattle and donkeys, has a lasting effect, and does not rebound after being cured once. The prescription of the invention does not expand the bag, and the tablet does not stick to the punch.

The effects and advantages obtained by combining experimental or experimental data with the prior art are:

10 cases of pigs in a farm of Zhengzhou city are selected, and the treatment results are compared by adopting the prescription and oxytetracycline tablets (0.05g) produced by commercial product Lizehongsheng pharmaceutical industry Limited.

Clinically, it can be divided into acute and chronic casesChronic endometritis。

(1)Acute endometritisObvious general symptoms, high body temperature of the sow, lassitude, anorexia or abominability, frequent liability, white mucus or foul red brown mucus flowing out of the vagina or foul red brown mucus flowing out of the vagina especially when the sow is just lying downPurulent nature Secretion materialThe secretion sticks to the root of the tail and smells bad. Sometimes the sow has abdominal pain symptoms. Acute diseaseMetritis of uterusIt is usually produced after parturition and abortion. (2) Chronic endometritis is mostly transformed from the untimely treatment of acute endometritis. The general symptoms of sick pigs are not obvious. The sick pig may periodically drain a small amount of turbid mucus from the vagina. Sows often delay oestrus or are in abnormal oestrus, and even if oestrus can be regularly developed, they are frequently infertile. And (3) curing: the symptoms are obviously improved or disappeared. The method has the following advantages: the symptoms are alleviated; and (4) invalidation: the symptoms did not improve significantly or did not improve.

Group of	Test examples	Number of cure	Is effective	Invalidation	Average days of administration
							Experimental group	10	8	2	0	2.5
Control group	10	6	2	2	4.8

Experimental groups: directly inserted into uterus of animals, 1 tablet at a time, 2 times a day.

Control group: directly inserted into uterus of animals, 16 tablets at a time, 2 times a day.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings needed to be used in the embodiments of the present application will be briefly described below, and it is obvious that the drawings described below are only some embodiments of the present application, and it is obvious for those skilled in the art that other drawings can be obtained from the drawings without creative efforts.

Figure 1 is a flow chart of a preparation method of a medicament containing doxycycline hyclate for treating metritis of an animal, which is provided by the embodiment of the invention.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

The medicament containing doxycycline hydrochloride for treating animal metritis provided by the prior art has the advantages of poor treatment effect, short action duration and easy relapse in healing effect. In addition, the medicine containing doxycycline hydrochloride for treating animal metritis provided by the prior art is easy to expand and stick.

Aiming at the problems in the prior art, the invention provides a medicament containing doxycycline hydrochloride for treating metritis of animals and a preparation method thereof, and the invention is described in detail with reference to the accompanying drawings.

The drug containing doxycycline hydrochloride for treating metritis of animals provided by the embodiment of the invention comprises 2.4-4 kg of doxycycline hydrochloride, 0.6-1.0 kg of lactic acid TMP, 1.5-2.5 kg of houttuynia cordata extract, 0.6-1.0 kg of angelica sinensis extract, 1.5-2.5 kg of herba patriniae extract, 1.5-2.5 kg of astragalus polysaccharide, 1.2-2.0 kg of scutellaria baicalensis extract, 10-14 kg of tartaric acid, 1.2-2.4 kg of sodium dodecyl sulfate, 8-12 kg of lactose, 12-20 kg of corn starch, 4kg of absolute ethyl alcohol, 20-30 kg of sodium bicarbonate mixture, 0.8-1.2 kg of magnesium stearate mixture and 2.4kg of carboxymethyl starch sodium by mass.

Preferably, the medicament containing doxycycline hydrochloride for treating metritis of animals consists of 3.2kg of doxycycline hydrochloride, 0.8kg of lactic acid TMP0.8kg, 2kg of houttuynia cordata extract, 0.8kg of angelica sinensis extract, 2kg of patrinia herb extract, 2kg of astragalus polysaccharide, 1.6kg of scutellaria baicalensis extract, 12kg of tartaric acid, 2.4kg of sodium dodecyl sulfate, 10kg of lactose, 16kg of corn starch, 4kg of absolute ethyl alcohol (prepared by 60% of ethanol), 24.15kg of sodium bicarbonate mixture, 1.020kg of magnesium stearate mixture and 2.4kg of carboxymethyl starch sodium by mass.

3.2kg of doxycycline hydrochloride, 0.8kg of lactic acid TMP0.8kg, 2kg of houttuynia cordata extract, 0.8kg of Chinese angelica extract, 2kg of patrinia herb extract, 2kg of astragalus polysaccharide, 1.6kg of scutellaria baicalensis extract, 12kg of tartaric acid, 2.4kg of sodium dodecyl sulfate, 10kg of lactose and 16kg of corn starch, mixing for 30min, and granulating with 60% ethanol of 14 meshes.

4000 tablets were prepared from the above total amount. The prepared tablet is as follows: 20 g/tablet.

Wherein, the medicine consists of 20kg of sodium bicarbonate, 2kg of motherwort extract, 2kg of ligusticum wallichii extract, 2kg of absolute ethyl alcohol and PVPK300.15kg.

The sodium bicarbonate mixture is composed of 20kg of sodium bicarbonate, 2kg of motherwort extract, 2kg of ligusticum wallichii extract, 2kg of absolute ethyl alcohol and PVPK300.15kg (for preparing a binder); the above components except for the adhesive are mixed for 30min and independently granulated into 14 meshes. PVPK30 was dissolved in 75% ethanol (prepared from 2kg of absolute ethanol).

The magnesium stearate mixture is composed of 0.9kg of magnesium stearate and 120g of borneol, and the borneol and the magnesium stearate are crushed together. Drying and adding.

In the invention, the hydrochloric acid polycyclocycline tablet-4000 tablets are as follows:

as shown in fig. 1, the preparation method of the medicament containing doxycycline hydrochloride for treating metritis of animals provided by the invention comprises the following steps:

s101, drying the granulated acid-base granules in an oven at the temperature of 60-65 ℃ for 3-5 h. Controlling the water content of the granules to be 3-4%, and finishing the granules with 12 meshes.

And S102, adding the acid-base granules together with the additional auxiliary materials of magnesium stearate, borneol and sodium carboxymethyl starch, mixing for 30min by using a two-dimensional mixer, and tabletting after the semi-finished product is qualified.

The invention is further described with reference to specific examples.

Example 1

The drug containing doxycycline hydrochloride for treating metritis of animals provided by the embodiment of the invention comprises 2.4kg of doxycycline hydrochloride, 0.6kg of lactic acid TMP0.6kg, 1.5kg of houttuynia cordata extract, 0.6kg of angelica sinensis extract, 1.5kg of herba patriniae extract, 1.5kg of astragalus polysaccharide, 1.2kg of scutellaria baicalensis extract, 10kg of tartaric acid, 1.2kg of sodium dodecyl sulfate, 8kg of lactose, 12kg of corn starch, 4kg of absolute ethyl alcohol, 22kg of sodium bicarbonate mixture, 0.8kg of magnesium stearate mixture and 2.4kg of carboxymethyl starch sodium by mass.

Example 2

The medicine containing doxycycline hydrochloride for treating metritis of animals provided by the embodiment of the invention comprises 4kg of doxycycline hydrochloride, 1.0kg of lactic acid TMP1, 2.5kg of houttuynia cordata extract, 1.0kg of angelica sinensis extract, 2.5kg of herba patriniae extract, 2.5kg of astragalus polysaccharide, 2.0kg of scutellaria baicalensis extract, 14kg of tartaric acid, 2.4kg of sodium dodecyl sulfate, 12kg of lactose, 20kg of corn starch, 4kg of absolute ethyl alcohol, 30kg of sodium bicarbonate mixture, 1.2kg of magnesium stearate mixture and 2.4kg of carboxymethyl starch sodium by mass.

Example 3

The medicine containing doxycycline hydrochloride for treating metritis of animals provided by the embodiment of the invention comprises 3kg of doxycycline hydrochloride, 0.8kg of lactic acid TMP0.8kg, 2kg of houttuynia cordata extract, 0.8kg of angelica sinensis extract, 2kg of patrinia extract, 2kg of astragalus polysaccharide, 1.5kg of scutellaria baicalensis extract, 13kg of tartaric acid, 2kg of sodium dodecyl sulfate, 10kg of lactose, 15kg of corn starch, 4kg of absolute ethyl alcohol, 25kg of sodium bicarbonate mixture, 1.0kg of magnesium stearate mixture and 2.4kg of carboxymethyl starch sodium by mass.

The invention is further described below in connection with pharmacological assays.

Chinese angelica:

[ pharmacological actions ]

The effect of (1) reducing platelet aggregation and antithrombotic effect of angelica on platelet aggregation is obvious inhibition effect of angelica on platelet aggregation, the angelica decoction is 100-500 mg/ml, ADP and collagen-induced rat platelet aggregation can be inhibited in vitro, after 20g (crude drug)/kg 5 min of the product is statically injected, the angelica decoction has obvious inhibition effect on ADP and collagen-induced rat platelet aggregation, 3H-5 HT labeled platelet experiment shows that 500mg/ml of the angelica decoction has obvious inhibition effect on thrombin-induced platelet aggregation, many experiments prove that ferulic acid can inhibit various inducers (such as arachidonic acid, epinephrine, ADP, platelet activating factor, calcium ion carrier A23187, collagen and thrombin and the like) from inducing platelet aggregation and release reaction of human, rabbit and rat, the prepared inducer can inhibit platelet aggregation IC50 of platelet aggregation caused by the prepared inducer between 0.036-5.0 mmol/L, the platelet aggregation inhibiting effect of angelica sinensis is obviously reduced by the inhibition effect of platelet aggregation of angelica, the platelet aggregation is obviously inhibited by the inhibition effect of platelet aggregation of the platelet aggregation of aspirin, platelet aggregation of angelica free aspirin and platelet aggregation of aspirin, the platelet-induced by the rat platelet-induced by the addition of aspirin, the antihypertensive enzyme, the platelet aggregation inhibitor of the antihypertensive enzyme, the.

(2) The Chinese angelica is the key Chinese medicine for enriching blood and invigorating blood circulation, and has high curative effect in clinical and experimental research. The Chinese angelica water extract can obviously promote the generation of hemoglobin and red blood cells when being orally taken by mice. The anti-anemia effect may be related to vitamin B12, nicotinic acid, leucovorin, biotin, folic acid, etc. Research shows that sodium ferulate has the effect of resisting the oxidation of gadolinium and H2O2 on erythrocytes, so that the membrane lipid peroxide Malondialdehyde (MDA) is reduced, and the hemolytic effect caused by OH and MDA can be obviously reduced. In the presence of sodium ferulate, lipid peroxide MDA of erythrocyte of sickle anemia patient is reduced with the increase of sodium ferulate concentration, sodium ferulate can obviously reduce complement hemolysis, and inhibit the combination of complement 3b (C3b) and erythrocyte membrane; has no influence on complement activation and erythrocyte degeneration. The angelicae sinensis polysaccharide has no obvious influence on the total number of erythrocytes, hemoglobin and femoral nucleated cells of normal mice, but can increase leukocytes and reticulocytes. Has remarkable promoting effect on the recovery of the number of red blood cells, hemoglobin, white blood cells and femoral nucleated cells of anemic mice. The injection of angelica polysaccharide in mice can prevent the decrease of peripheral blood leucocyte of mice caused by prednisolone (prednisolone). The angelica polysaccharide has obvious proliferation stimulating effect on mouse in-vivo detection, single line progenitor cells (GM-CFU-D) and megakaryocyte progenitor cells. The mouse is injected with 2 per mill of angelica polysaccharide (0.2 ml/mouse, 1 time per day, 6 times in total) subcutaneously, has obvious stimulation effect on the proliferation of multifunctional hematopoietic stem cells (CFU-S), can promote erythroid cell differentiation, and can stimulate the proliferation of early erythroid progenitor cells (BFU-E) and late erythroid progenitor cells (CFU-E). The mechanism of the method is probably related to the activation of macrophages and lymphocytes, so that the erythropoiesis regulation factors with higher activity are secreted, and the erythropoiesis is promoted. In vitro culture also demonstrated that angelicae sinensis polysaccharide significantly stimulated the proliferation of granulosa, unilineage progenitor cells (CFU-GM) in normal and myelosuppressive anemic mice. These effects may be associated with the promotion of the secretion of granulocyte, monogenic colony factor (GM-CSF) by the body.

2. The effect on heart is (1) in vitro perfusion experiment of toad heart, the decoction or the volatile oil contained in its root and leaf can obviously inhibit the contraction amplitude and frequency, the fresh leaf decoction is slightly excited when the dosage is small, and the dosage is increased, so that the heart beat is inhibited until it stops at diastole. The inhibition of the Chinese angelica on the frog heart in vitro can be relieved by adrenalin, and atropine can also be relieved. When 2.08g (crude drug)/Kg (crude drug) of 50% angelica decoction is administrated through abdominal veins, complete atrioventricular block mostly appears in the heart of a toad in vivo, the atrial contractility is obviously weakened, and then gradually recovers, the frequency is reduced, but the ventricular contractility is strengthened. 2g/Kg of angelica extract can increase and then reduce the heart rate of anesthetized and kidney-conscious hypertensive dogs, the conscious dogs are obvious, and in vitro auricle-free experiments show that the angelica extract solution can slightly reduce the myocardial contractility and obviously prolong the refractory period, and the effect can be resisted by calcium chloride and adrenalin.

(2) The angelica extract has the functions of obviously expanding the isolated guinea pig coronary artery and increasing the coronary blood flow on the influence of the coronary flow and the myocardial oxygen consumption. 2 minutes after 2g/kg of the product is statically injected into an anesthetized mouse, when the heart rate does not change obviously, the coronary resistance and the total peripheral resistance are reduced, the coronary blood flow is increased obviously, the myocardial oxygen consumption is reduced obviously, the cardiac output and the cardiac index are increased, the work done by the left ventricle and the myocardial efficiency are not changed obviously, and the level before administration is recovered 5-10 minutes after administration. The angelica and angelica monkshood injection has the functions of reducing oxygen consumption and oxygen consumption rate and enhancing the hypoxia tolerance of animals to acute hypoxia animals under reduced pressure or normal pressure. The radix Angelicae sinensis fluid extract can increase 86Rb uptake ability of mouse myocardium. The ferulic acid can antagonize acute myocardial ischemia caused by hypophysin and acute myocardial infarction of rabbit caused by ligation, reduce oxygen consumption of isolated myocardium of guinea pig, increase 86Rb uptake of myocardium of mouse and coronary blood flow of isolated rabbit and guinea pig, and reduce myocardial contraction amplitude without affecting heart rate. The angelica sinensis injection can obviously reduce the myocardial infarction range when the anesthesia dog blocks coronary artery, and can resist the myocardial ischemia of experimental rabbits.

(3) The 1% solution of radix Angelicae sinensis fluid extract for resisting arrhythmia has therapeutic effect on atrial fibrillation of anesthetized dog caused by acetylcholine and anesthetized cat or dog caused by current. Angelica sinensis removes 3g/kg of K ten total extract for intravenous injection, has certain resistance to arrhythmia caused by epinephrine after 10 days, can slow down heart rate, reduce serious arrhythmia such as ventricular and supraventricular tachycardia, replace occasional premature contraction, and has better recovery of electrocardiogram compared with that before administration, but has no resistance to ischemic electrocardiogram change caused by epinephrine and has certain effect on arrhythmia caused by hypophysis posterior lobe. Has no obvious effect on arrhythmia caused by aconitine or chloroform. In an in vitro guinea pig ventricular muscle experiment, the angelica alcohol extract and the angelica A injection (sodium ferulate injection) can resist the stropanthus divericatus and arrhythmia caused by ouabain poisoning and convert the stropanthus divericatus and ouabain poisoning into normal rhythm, but in the whole experiment, only the preventive application of the angelica alcohol extract has a remarkable effect on ventricular fibrillation caused by ouabain poisoning, and can delay the ventricular fibrillation and improve the fibrillation threshold. Intravenous injection of 10mg/kg sodium ferulate can antagonize chloroform and epinephrine induced cat, bird head alkali induced rat, ouabain induced guinea pig arrhythmia, and cardiac glycoside induced ventricular inorhythmia of ampullate guinea pig. Electrophysiology research proves that the angelica alcohol extract has the excellent effect similar to quinidine, and also obviously prolongs the plateau phase, and supposing that the antiarrhythmic effect of the angelica alcohol extract is the result of multiple effects of slowing down conduction, prolonging the effective refractory period, eliminating reentry, prolonging the plateau phase, inhibiting ectopic rhythm points, improving the threshold of fibrillation and the like. When sodium ferulate is perfused for 30 minutes, the Action Potential Amplitude (APA) and repolarization 20% time interval (APD20) have no obvious change, but the action potential time interval (APD90) and effective refractory period at the position of 90% of the repolarization are prolonged.

(4) The effect of 25% angelica decoction on blood vessel, blood pressure and organ blood flow is that when toad blood vessel perfusion is carried out, the effect of contracting blood vessel is achieved, when auricular blood vessel perfusion is avoided, blood vessel is dilated, when 2% angelica extract Rockwell fluid of Kten is removed, the auricular blood vessel in vitro is obviously prevented, the flow is obviously reduced, the contraction of aorta smooth muscle of isolated rabbit caused by potassium chloride cannot be resisted, when water extraction alcohol precipitation solution is 1-4 g (crude drug)/Kg intravenous injection is carried out, the arterial blood pressure of an anaesthetized dog is obviously reduced, at the moment, the resistance of coronary artery, cerebral artery and femoral artery is reduced, the blood flow is obviously increased, the effects of increasing peripheral blood flow and reducing vascular resistance are enhanced along with the increase of drug dosage, when water extraction alcohol precipitation injection of 10-40 mg (crude drug)/Kg is carried out on femoral artery injection, the blood flow of femoral artery is obviously increased, the blood pressure change is not obvious, the dilatation effect of angelica on peripheral blood vessel is not affected by propranolol or phentolamine, but atropine and the blood vessel dilatation effect of the antihypertensive drug injection is not related to the vasoconstriction of arteria sinensis receptor of rat, when the femoral artery injection is carried out, the blood pressure reduction, the blood vessel is not related to the blood pressure reduction, the blood vessel, the blood pressure of the rat, the hypertension of animals, the hypertension of the rat is not related to the rat, the hypertension of animals, the rat, the hypertension of the rat, the hypertension, the rat is not related to the hypertension, the hypertension of the rat, the.

3. Blood lipid lowering and arteriosclerosis affecting: 1.5g/kg of angelica powder has the function of reducing blood fat for rat and house immunity experiment hyperlipemia, and the function of reducing blood fat is not caused by the obstruction of the absorption of cholesterol. The food containing 5% of radix Angelicae sinensis powder, and the corresponding amount of radix Angelicae sinensis oil and other extracts has certain protective effect on diseased aorta of experimental arteriosclerosis rat. When 0.2% (W/W) ferulic acid is added into high-fat food and fed to rats for 4 weeks, the increase of serum cholesterol level can be obviously inhibited, but triglyceride and phospholipid levels are not affected.

The ferulic acid can compete with mevalonic acid-5-pyrophosphoric acid (substrate), and can inhibit the mevalonic acid-5-pyrophosphoric acid dehydrogenase of rat liver in a concentration-dependent manner, the enzyme activity is inhibited by 74% at the concentration of 2.5 mmol/L, which indicates that the ferulic acid has the effect of inhibiting liver from synthesizing cholesterol.

4. Antioxidant and scavenging free radical effects, the reaction process that dimethyl sulfoxide generates superoxide anion free radical (O2) under the alkaline aerobic condition is directly observed by using an electron paramagnetic resonance method, a model system for generating O2 & is added with angelica sinensis water decoction, the result (O2 & is 96%. angelica sinensis has a very significant activation effect on human blood superoxide dismutase (SOD) in vitro, various methods prove that ferulic acid is an antioxidant, hydroxyl on a benzene ring of ferulic acid molecules is an antioxidant active gene, can inhibit the generation of lipid peroxide of ultraviolet irradiation linoleic acid and human microsomes, inhibit oxidative deterioration caused by heating soybean oil, remarkably enhance the induction period effect of hydroxy-butyrate, histidine or aspartic acid for prolonging the oxidation of linoleic acid in the absence of antioxidant effect at an antioxidant concentration of the antioxidant effect, sodium ferulate has a protective effect on myocardial ischemia reperfusion injury of rats, can obviously reduce the activity of membrane Ca2+ -enzyme, reduce the content of free fatty acid and the ratio of phospholipid/cholesterol, improve the ratio of the mitochondrial membrane, inhibit the generation of myocardial ischemia reperfusion injury of rats, inhibit the generation of myocardial ischemia reperfusion injury of rat, and reduce the pathological reaction of myocardial membrane cholesterol, inhibit the cholesterol generation of cholesterol oxidase, inhibit the cholesterol production of rat plasma cholesterol, inhibit the cholesterol production of cholesterol, inhibit the.

5. The clinical application of the angelica sinensis blood enriching soup injection can improve the cellular immune function of a patient after brain tumor operation, the angelica sinensis blood enriching soup and single medicines thereof have obvious promotion effect on the T lymphocyte function of a mouse, 5 percent of angelica sinensis polysaccharide is subcutaneously administered according to 250mg/kg, 1 time per day for 7 consecutive days, the E-rosette formation rate and the acid α -naphthol acetic esterase staining positive rate of the mouse are obviously higher in an experimental group than in a control group, and the angelica sinensis polysaccharide can obviously improve the immune function of the mouse, however, the intramuscular injection of the angelica sinensis polysaccharide is reported, the angelica sinensis injection (0.05g of a syngen drug is equivalent to each 1ml, the main chemical component is butylphthalide), the intramuscular injection of the angelica sinensis polysaccharide is 0.25g/kg, the delayed hypersensitivity reaction caused by 8 days to a normal mouse is found without stimulation or inhibition, the addition of Kumazawa and the like by using a 3H-thymidine addition method is used for measuring the difference of the angelica sinensis polysaccharide on the T lymphocyte proliferation, and the difference of the lymphocyte proliferation of the splenocyte proliferation is probably related to the thymocyte proliferation condition that the thymic cell proliferation is not doped with thymidine.

(2) The experiment shows that 30-100 mu g/0.2ml of immune active polysaccharide of angelica sinensis stimulates 3H-TdR of cultured splenocytes of C57B L/6 mice and humans, and the experiment shows that the immune active polysaccharide (AIP) or lipopolysaccharide (L PS) is added or not added, and the hemolytic plaque method is used to determine the influence of plaque forming cell numbers (PFC) on T cell dependent antigens (SRBC) and T cell independent antigens (trinitrobasic TNP, TNP) in mice and mice, the AIP and 32 PS can obviously increase the numbers of anti-SRBC, PFC and anti-TNP, PFC, and anti-TNP, such as in a culture system, the removal of T cells or lymph cells, the influence of the anti-HBsAP forming cell numbers (PFC), the result shows that the effect of anti-SRBC, PFC, anti-TNF, and anti-TNF, the anti-HBP is obviously increased when the anti-HBP antibody is injected in abdominal cavity, the mouse, the anti-HBP antibody is injected in vitro, the mouse, the antibody is injected by 25mg/d, the antibody of ASDP, the antibody of the mouse, the antibody of ASDP, the antibody of anti-HBP, the mouse, the antibody of the mouse, the mouse spleen, the mouse, the antibody of anti-HBP, the mouse.

(3) Effect on the function of the monocyte phagocytic system the clearance of 131I plasma protein colloidal particles in mouse serum was used as an indicator of the phagocytic function of monocytes, and as a result, it was found that angelicae gigantis radix has the function of promoting phagocytosis. The 5% angelica polysaccharide is administrated subcutaneously to mice, can obviously enhance the phagocytosis function of mouse abdominal cavity macrophages (Mp) on Chicken Red Blood Cells (CRBC), and can also antagonize the inhibition effect of cyclophosphamide on the phagocytosis function of mouse abdominal cavity Mp. The angelica can obviously improve the Mp function of experimental animals and the clearance rate of reticuloendothelial system to the dye congo red in serum, and the ferulic acid also has similar effect. The angelica sinensis blood-enriching soup and the single medicine thereof have the function of promoting the Mp function of mice. The 50mg/kg celiac administration of Angelica sinensis polysaccharide can not only improve mononuclear phagocyte function of normal mouse, but also antagonize suppression state of mouse immunoreaction caused by prednisolone (prednisolone), and prevent leukocyte decrease caused by immunosuppressant in peripheral blood. The angelica sinensis extract ASDP and ASDE3, when administered in the abdominal cavity of a mouse, have obvious activation effect on the activity of the mouse abdominal cavity lysosome enzyme system, and the activities of acid phosphatase and N-acetylglucosamine are higher than those of a control group. The same in vivo test is used to research the effect on Mp cell membrane enzyme system in mouse abdominal cavity, and the result shows that ASDP/ASDE3 has immunoregulation effect on alkaline phosphatase and alkaline phosphodiesterase. The angelica has obvious enhancement effect on the non-specific phagocytic function of the damaged Mp of a diabetes model mouse, the optimal concentration of the angelica is 440 mug/gml, and the hyperglycemic state has no obvious interference on the effect of the angelica on the damaged M9.

(4) The induction effect on cell factors is 5% angelica injection (initial concentration is 12.50mg/ml, and the latter is 4 times decreased), the injection has obvious enhancement effect on the generation of interleukin 2(I L-2), the strongest effect is achieved at the concentration of 0.20mg/ml, PGE210-6 mol/L or PGE2 and angelica 0.78mg/ml are added singly, the generation of I L-2 is inhibited strongly, the inhibition degree of the two conditions is similar, in a culture system, if not adding mitogen concanavalin A (ConA), the angelica can not induce the generation of I634-2, therefore, the angelica only changes the responsiveness of rat T cells to COnA, can not antagonize the inhibition effect of PGE2 on I L-2, the induction effect of angelica on I L-2 can not be achieved through the route of 539E 2, but can be achieved through the direct activation effect on Th cells, the inhibition effect of the resting of angelica on I L-2, the IFN-activating protein I, the splenic acid activating protein I-9, the splenic acid activating protein I-3, the IFN-activating protein-3, the splenic acid activating protein-I-2, the IFN-activating protein-beta-.

6. Effects on allergy: 70mg/Kg and 140mg/Kg of ferulic acid are injected into the abdominal cavity to inhibit the allergic reaction of the same passive skin of the rat, the degranulation of the mast cells of the rat and the active and passive Arthus reaction; 140mg/kg inhibits reverse skin allergic reaction of rats and Forssman cutaneous vasculitis of guinea pigs; 1100mg/kg and 200mg/kg inhibit delayed type hypersensitivity of mice; the phagocytic function of the mouse mononuclear macrophages is improved by oral administration of 200mg/kg and 400 mg/kg. The ferulic acid is shown to have inhibition effect on A, II, III and IV type allergic reactions.

7. The effect on the fertility function (1) the effect on the uterus of various animals in vitro, in vivo uterus and chronic uterine fistula tests prove that the angelica has a bidirectional effect on the uterine muscles, the high boiling point (180-210 ℃) volatile oil of the angelica has an inhibitory effect on the uterus at a concentration of 1: 50, the effect is rapid and lasting, the uterine contraction is reduced, the uterus is relaxed, the contraction can be completely stopped at a concentration of ⒈, the uterine contraction is recovered after washing away the liquid medicine, and no obvious damage is caused to the uterus, the angelica volatile oil can resist the excitatory effect of adrenalin, pituitary phyllodulin or histamine on the uterus, the inhibitory effect still appears after atropine is sunburned, so the inhibition on the uterine muscles is 4 possibly direct effect, the water or alcohol soluble nonvolatile substances of the angelica have an excitatory effect on the H body, the uterine contraction is strengthened, the uterine contraction can occur when a large amount of medicines or multiple times of medicines are taken, the alcohol soluble substances have a stronger effect than the water soluble substance effect on the water soluble substance, the hydrostatic effect on the uterine contraction occurs, the weight of the volatile oil and the nonvolatile components of the angelica have an effect on the uterine contraction after injection, the uterine contraction is proved that the uterine contraction is obviously improved by the uterine glucose metabolism, the uterine contractility of the uterine glucose receptor is improved by rabbit, the intrauterine glucose metabolism is obviously, the intrauterine glucose metabolism is improved, the intrauterine fertility receptor is improved by the intestinal hypertrophy, the prostaglandin receptor is proved by the urinary tract is obviously, the urinary tract is improved by the urinary tract.

(2) The effect of inhibiting prostate weight gain is continuously injected subcutaneously for 5-10 days or orally taken with 2.5-6 Kg/piece or 25ng/Kg and 50mg/Kg of ferulic acid, and can antagonize the prostate weight gain effect of exogenous androgen on castrated male rats and normal male rats with endogenous androgen. By continuous subcutaneous injection of ferulic acid at 10mg/kg, 25mg/kg or 50mg/kg into male rats, it was found that dose-dependent inhibition of prostate weight gain and reduction of polyamine content in the prostate was possible due to the reduction of putrescine, spermidine and spermine in the polyamines and the decrease of the spermidine/spermine ratio, presumably due to the inhibition of ornithine decarboxylase. The prostate is a tissue with high polyamine content, and ferulic acid causes prostatic atrophy by inhibiting this enzyme, which selectively causes the decrease in the polyamine content of the prostate.

(3) Ferulic acid, which acts against gonadotropic hormone, inhibits the secretion of luteinizing hormone and prolactin from the pituitary gland, and also antagonizes gonadotropin-stimulating hormone release, thereby causing luteal lesions in females and a decrease in plasma progesterone levels, resulting in abortion, and a decrease in testosterone release in males.

8. Radiation damage resistance: the angelica has obvious effect of resisting radiation damage. When angelica is used for carrying out intraperitoneal injection on the rabbits with radiation injury, the chromosomal aberration rate of the rabbits is obviously reduced, the chromosomal aberration rate is completely recovered to be normal after 9 days of continuous injection, and the experimental result of the external use medicine is the same as the in vivo injection result. The angelica injection is administered to the abdominal cavity of the mouse after being irradiated by 60 Co-gamma rays for 30 consecutive days, and the ovary after being irradiated and damaged starts to enter the recovery period at the 15 th day after being irradiated, which is obviously earlier than that without the angelica. The female mice of the drug group were mated with male mice with reproductive capacity 30 days after irradiation, and still 80% could be bred. The angelica polysaccharide has a certain radiation protection effect on hematopoietic tissues of an irradiated mouse when the angelica polysaccharide is given prophylactically, can obviously promote the recovery of hematopoietic functions of bone marrow and spleen, prevent secondary atrophy of thymus, and also can improve the survival rate of the irradiated mouse for 30 days, has the radiation protection effect on hematopoietic cells of the irradiated mouse, can increase the formation of endogenous hematopoietic foci of the spleen of the irradiated mouse by injecting the angelica polysaccharide before irradiation, improve the bone marrow nucleated cell count of the irradiated mouse, has less influence on the radiation sensitivity of CFV-C and CFV-S, can prevent the effect after irradiation, and can obviously promote the recovery of CFV-S and CFV-C of the mouse, which is probably one of the principle of the radiation resistance.

9. The anti-tumor effect is that five kinds of polysaccharide of Minxian county angelica are screened for anti-tumor medicine in mice, and the result shows that the polysaccharide has certain inhibition effect on mouse transplantation tumors EC, Hep, S180, L ewis, B16 and the like, the tumor growth inhibition rate can reach 39%, the side effect is less, and the polysaccharide can be taken for a long time.

10. Anti-inflammatory analgesic and anti-injury effects: the angelica water decoction has obvious inhibition effect on acute and chronic inflammations caused by various inflammation causing agents, and the anti-inflammatory effect still exists after the adrenal glands on both sides are removed; and can reduce the release amount of PGE2 in rat inflammatory tissues and reduce the hemolytic activity of guinea pig complement alternative pathway, but can not antagonize the inflammatory action of limbs. The water extract of the product can reduce vascular permeability, and the mouse oral administration 185.9Mg (crude drug)/Kg has equivalent blood permeability ID50 to the oral administration of sodium acetylsalicylate 201.lmg/Kg, i.e. the effect is 1.1 times of the latter, and the sodium acetylsalicylate can inhibit the release of inflammation-causing substances such as 5-hydroxytryptamine (5-HT) in blood platelets, thereby generating anti-inflammatory effect. The water extract of angelica sinensis can inhibit passive skin allergy PCA reaction and leakage of pigment of rats when being taken orally. The ID50 of the product water extract and sodium acetylsalicylate for writhing reaction caused by injection of acetic acid into abdominal cavity is 65.9 mg/Kg and 114.3mg/Kg respectively, which indicates that the analgesic effect strength of the product is 1.7 times of that of sodium acetylsalicylate. Chinese angelica and Japanese angelica have obvious anti-injury function, and the angelica is orally taken or locally applied to rabbit acute edema caused by different reasons, and shows the anti-edema function.

11. Action on digestive system: angelica sinensis has certain effects of protecting liver cells and restoring certain functions of the liver. For rat acute liver injury caused by carbon tetrachloride, the inflammatory reaction can be obviously relieved, and serum transaminase is slightly reduced; for the induced liver cirrhosis, the collagen content of liver tissue can be reduced, and the degree of cirrhosis can be reduced. For rats with partial excision, angelica can increase the nuclear division phase index of liver tissue, so that the Chinese angelica has certain effect of promoting liver regeneration. The angelica has obvious protective effects on liver cell damage (the activity of 5' -nucleotidase and ATP enzyme is reduced) and liver cell mitochondria damage (the activity of succinate dehydrogenase is reduced) of acute liver injury of rats caused by D-galactosamine; improving histochemical changes of endoplasmic reticulum damage (increased glucose-6-phosphatase activity) of the liver cells; has antagonistic effect on reduction of glycogen content in monthly thousand. The water extract, volatile oil or sodium ferulate of radix Angelicae sinensis have effect in promoting bile secretion of rat, and increasing solid substance in bile and bile acid excretion. The gallbladder-normalizing action of Dang Gui is probably related to its general improvement and digestion-promoting action. Ferulic acid 400mg/kg and Ferulic acid 800mg/kg can inhibit castor oil induced diarrhea of mice without affecting senna leaf induced diarrhea of mice, and inhibit gastrointestinal propulsion of mice. The fluid extract of angelica and the leaves thereof has the effect of inhibiting the intestinal muscles of in vitro rabbits. The volatile oil has effect in inhibiting in vitro intestinal segment contraction caused by acetylcholine.

12. Other effects the angelica volatile oil component ligustilide has inhibiting effect on the central nervous system, can reduce the spontaneous activity of mice, shorten the sleep time of pentobarbital sodium and prolong the sleep duration; against the central excitatory action of ketamine; inhibit the irritability reaction induced by the electric stimulation and can obviously reduce the body temperature of the mouse. Ligustilide has effect in relaxing airway smooth muscle. The intraperitoneal injection of 0.14ml/kg in guinea pig can relieve the asthmatic reaction of histamine and acetylcholine. In guinea pig lung overflow experiments, intravenous injection of 0.08ml/kg of britannin can resist bronchoconstriction caused by histamine 2-10 mug/g. H-lactone not only has relaxation effect on isolated tracheal strips of guinea pigs, but also has obvious spasmolysis effect on bronchosmooth muscle spasm and contraction caused by acetylcholine, histamine and barium chloride. Angelica sinensis has diuretic effect, and its crude preparation has exciting effect on bladder smooth muscle. The angelica can improve the glomerular filtration function and the renal tubule reabsorption function after 60 minutes of home-use renal heat ischemia prevention, relieve renal damage, promote the recovery of renal tubule lesions and have certain protection effect on the kidney. When 5-6% of the angelica is fed to the white mice, the white mice have certain protection effect on testicular lesion caused by the lack of vitamin E. In addition, the angelica volatile oil has better effect on preventive administration or treatment after infection of mice infected by staphylococcus aureus, escherichia coli, shigella flexneri, pseudomonas aeruginosa and the like.

13. The toxicity of the angelica is low, L D50 of the mouse injected with angelica intravenously is 80-100 g/kg, 298mg/kg and 960 mg/kg of volatile oil subcutaneously and L D50 of intragastric administration are 298mg/kg and 960 mg/ground respectively, L D50 of the ligustilide intraperitoneal injection is 520mg/kg, L D50 of sodium ferulate intravenously and intragastric administration is 1.7g/kg and 3.6 g/kg. of the mouse injected with angelica intravenously, the mouse fed with the 5% angelica diet has no obvious influence on liver, kidney, electrocardiogram and hemogram for 14 days continuously, the animals grow well after 3 months and 5 months, and the capacity of oxidizing glutamic acid by the liver is obviously improved.

Ligusticum wallichii:

[ pharmacological actions ]

1. Effects on the cardiovascular and cerebrovascular System: (1) action on heart ligustrazine extracted from rhizoma Ligustici Chuanxiong has dose-dependent inhibitory effect on isolated guinea pig heart, but has little influence on heart rate. Before and during hypoxia, ligustrazine has effects of reducing myocardial contractility, decreasing diastolic function, and slowing down heart rate. Has cardiotonic effect on ligustrazine of whole animal. The ligustrazine intravenous drip for anesthetized dogs has the effects of increasing heart rate, strengthening myocardial contractility and the like, and the effects are strengthened along with the increase of dosage. Infusion of ligustrazine into conscious hypertensive dogs also causes an increase in heart rate. Ligustrazine 10mg/Kg, 20mg/Kg and 30mg/Kg for intravenous injection can remarkably accelerate heart rate of anesthesia dog, shorten Q-T interval of electrocardiogram, and reduce ST segment; 20mg/kg and 30mg/kg enable inversion of the T-wave or the appearance of a biphasic T-wave. However, experiments show that the ligusticum wallichii 5-20 mg/Kg has no remarkable effect on the cardiac function of the anesthetized thoracotomy cat, 40mg/Kg can inhibit myocardial contraction, but the cardiac output, the cardiac index and the stroke index are not reduced, and 80mg/Kg has a remarkable effect on the cardiac function. 320 mu g/kg of ligusticum wallichii has obvious inhibition effect on Ca2+ inflow in cultured myocardial cells of suckling mice. Observation of the varietal effect of isolated papillary muscle, recording of the transmembrane action potential of the sinoatrial node and observation of the varietal effect of Escherichia coli and body surface electrocardiogram show that ligustrazine has negative inotropic effect, negative frequency conversion and varietal effect, and is very similar to verapamil (verapamil) in characteristics, and it is presumed that ligustrazine may be a calcium ion antagonist.

(2) Effects on blood vessels and blood pressure ligustrazine can produce blood pressure lowering effects to different degrees when different administration routes (intravenous injection, intravenous drip or duodenal administration) are used for various animals (cats, rabbits and rats) and different doses are used for the ligustrazine, the effects of the ligustrazine on the contraction of thoracic aorta strips induced by norepinephrine, potassium chloride and calcium chloride are very similar to those of verapamil, the blood pressure lowering effects of the ligustrazine can be mainly caused by direct blood vessel expansion, the ligustrazine can expand pulmonary vessels of rats, inhibit the hypoxic pulmonary vasoconstriction reaction and right ventricular hypertrophy, the maximal rate of change of right ventricular pressure (± dp/dtmax) is not significantly influenced, the ligustrazine can also reduce acute hypoxic pulmonary hypertension and pulmonary vascular resistance of dogs, but has no influence on body circulation, isolated rat pulmonary artery loop experiments show that the ligustrazine can significantly reduce the responsiveness of pulmonary artery loop to epinephrine (NE), the pulmonary artery synthesis release of tetracycline (PGI2) is promoted, the pulmonary artery synthesis release of tetracycline (PGI) is in a dose-dependent relationship, the indomethacin (indomethacin) can significantly inhibit the smooth arterial vasoconstriction of the smooth arterial blood vessels of the rat, the rat's in vitro vasoconstriction of rat's, the rat's smooth vascular endothelial cells can significantly reduce the effects of rat's smooth arterial constriction of rat's smooth vascular constriction, the rat's smooth vascular endothelial cells, the rat's vascular endothelial cell activation has the effects of rat's (rat's vascular endothelial cell activation, the rat's vascular endothelial cell activation has the effects of rat's vascular endothelial cell activation, the rat's vascular endothelial cell activation has the rat's vascular endothelial.

(3) Influence on coronary flow rhizoma Ligustici Chuanxiong and ligustrazine have significant effect in increasing coronary flow for heart of the free rat or guinea pig.

(4) The effects of ligustrazine intraperitoneal injection and ligusticum wallichii core intragastric administration on myocardial ischemia and reperfusion injury can prolong the survival time of mice in a low-pressure anoxic environment and resist acute myocardial ischemia and anoxia of rabbits caused by pituitrin. The ligustrazine injection 2ml/kg can increase endogenous superoxide dismutase (SOD) activity of organism, reduce Malondialdehyde (MDA) level, and prevent and treat hemorrhagic shock reperfusion injury of rabbit. Ligustrazine also has preventive and protective effects on isolated rat myocardial ischemia and reperfusion injury model. But can increase myocardial oxygen consumption for the ligustrazine, can sharply enlarge the infarction range and aggravate the degree of myocardial ischemia in the acute coronary occlusion period of the dog, and has no obvious beneficial effect on the hemodynamics.

(5) Chuanxiongzine 4mg/Kg can expand cerebral blood vessel by intravenous injection, reduce vascular resistance and increase cerebral blood flow obviously for treating atherosclerosis, cerebral vascular dynamic parameter diseases such as average blood flow, average blood flow rate decrease and peripheral resistance increase of cerebral blood vessel, and cerebral vascular function protection, etc. Chuanxiongzine has obvious effect of preventing and treating cerebral pia mater microcirculation disturbance caused by high molecular weight anhydroglucose, and for ischemia reperfusion injury model of sand and earth mice, it has the effect of inhibiting oxygen free radical from damaging brain tissue, reducing neuron and capillary endothelial cell damage, and improving nerve sign, etc. in addition, Chuanxiongzine has the effect of promoting recovery of ischemic brain injury of dogs, antagonizing secondary peripheral blood pressure and pulmonary blood vessel pressure increase after ischemia, and may be a better protective agent for resisting cerebral ischemia/reperfusion injury, and the injection can obviously improve thrombocyte of Qiangkephalin plasma and cerebrospinal fluid of rabbits after cerebral ischemia, and strong morphine peptide A1-13-like immunocompetent substance (ir-Dy 1-13) content change, reduce damage and nervous system damage, and inhibit TXyloglobulin function of ischemia platelet (TG) and increase TX5934) and platelet protection (TG) of platelet, thus, it has obvious effect of protecting cerebral ischemia-GCA, and improving cerebral ischemia.

(6) The effects on microcirculation such as rhizoma Ligustici Chuanxiong and ligustrazine can relieve the spasm of the cheek pouch, vein and capillary vessel of golden hamster caused by norepinephrine, accelerate the slowed blood flow, and increase the reduced blood flow. The rhizoma ligustici wallichii has obvious effect of delaying the occurrence of microcirculation disturbance such as the stopping or slowing of arteriolar blood flow, the contraction of pipe diameter and the like caused by epinephrine and has the effect of expanding arterioles. The ligustrazine 40mg/Kg is injected for intravenous injection to increase mesenteric microcirculation blood flow and open number of capillary, and the injection of 10% Chuanxiong injection 10ml/Kg and intramuscular injection of 20% Chuanxiong injection 1ml/Kg can improve acute and chronic bulbar conjunctiva and pia mater microcirculation disturbance of rabbit caused by injection of 10% high molecular dextran.

2. Influence on blood system rhizoma Ligustici Chuanxiong and rhizoma Ligustici Chuanxiong howls have remarkable inhibitory effect on platelet aggregation of rabbit induced by ADP, collagen and thrombin in vitro, and can rapidly depolymerize aggregated platelets. Meanwhile, the preparation method can also inhibit the generation of platelet malondialdehyde, and has no inhibition effect on exogenous arachidonic acid-induced platelet aggregation. The ligustrazine can enhance the inhibition effect of the rabbit arterial environment-friendly warm liquid on the arachidonic acid-induced platelet aggregation. Ligustrazine can inhibit platelet activation and arterial thrombosis in extracorporeal circulation, and also can significantly inhibit platelet aggregation and release of allergic asthma guinea pig dlk. The composition has a strong inhibiting effect on platelet aggregation and TxA2 synthesis of septicemic rabbits and ligusticum wallichii, and also has a strong inhibiting effect on aggregation of neutrophils in the lung. The mechanism of ligustrazine for inhibiting platelet aggregation is probably related to the effects of inhibiting the release of intracellular Ca2+, influencing the balance between TxA2/PGI2, replacing Ca2+ on platelet membranes, increasing negative charges of the membranes, inhibiting platelet aggregation, inhibiting phosphorylation of phosphatidylinositol-Phosphate Intermediate Phosphate (PIP) kinase and 20K protein in platelets and the like. Chuan Xiong indole and Chuan Xiong injection can respectively increase cAMP level of mouse plasma and rabbit platelet suspension. Ligustrazine inhibits thrombin-induced aggregation between mononuclear cells and platelets, and is in a dose-effect relationship. The ligusticum wallichii injection can obviously reduce the adhesion of white blood cells on the vein wall of a scalded rabbit, delay and reduce the aggregation of erythrocytes in microcirculation, reduce the adhesion rate and aggregation reaction of platelets, prevent the viscosity of whole blood from rising, and obviously improve the rheological property of scalded blood. Ligustrazine has effects of improving rabbit erythrocyte deformation and reducing whole blood viscosity. After the patient with cardiovascular and cerebrovascular diseases takes ligustrazine, the rheological property of blood can be obviously improved, the viscosity of blood is reduced, the surface charges of erythrocytes and blood platelets are increased, the aggregative property is reduced, the content of fibrinogen is reduced, etc. Ligustrazine has urokinase-like effect, and can directly activate plasminogen without fibrinolytic enzyme activity. In addition to inhibiting platelet aggregation, the ligusticum wallichii can also inhibit in-vitro thrombus formed by the Chandler method, prolong the thrombus formation time, shorten the thrombus length and reduce the wet weight of the thrombus, but has no change on the dry weight. In addition, ligustrazine has inhibitory effect on thrombosis formed in rat artificial arteriovenous shunt, and has no inhibitory effect on thrombosis caused by thrombin in auricle-free vein. The rhizoma chuanxiong eosin has the effect of improving the activity of erythrocyte SOD on aged mice and pulmonary edema rats.

3. The ligusticum wallichii triazine action on the urinary system can obviously increase the renal-free blood flow volume, the action of the ligusticum wallichii triazine is dependent on the medicament dosage, and the ligusticum wallichii triazine derivative has obvious diuretic effect. Ligustrazine has certain prevention and treatment effects on rabbit Masugi nephritis, experimental membranous nephritis and rat orthotopic nephritis, and the mechanism of ligustrazine is related to factors such as platelet aggregation resistance, improvement of blood rheological property, influence on prostaglandin metabolism, improvement of oxidation resistance of organisms and the like. Has good protective effect on acute nephrotoxicity caused by the cyclosporin A and chuanxiong rhizome or chuanxiong rhizome crash. Ligusticum wallichii can prevent acute renal failure of rabbits caused by glycerol, the effect may be related to functions of Ligusticum wallichii for increasing renal blood flow, enhancing synthesis of prostaglandin in renal medulla, correcting PGI2/TxA2 imbalance and protecting renal tubules from reabsorbing sodium, and the active ingredients playing the role may be in volatile oil. In addition, the rhizoma ligustici wallichii can inhibit the entry of Ca2+ to rat renal proximal tubule epithelial ischemic cells, so that the plasma membrane and mitochondrial injury is relieved, and the rhizoma ligustici wallichii has a protective effect on ischemia.

4. The ligusticum wallichii can improve the T lymphocyte transformation function of mice with low cellular immune function caused by normal mice and lymphocyte serum (A L S), can adjust the function of the suppressor T cells (Ts) which are abnormally increased by the mice A L S to a normal level, and can also improve the activity of the mouse interleukin-3 (I L-3) which is abnormally increased by the mice A L S.

5. The ligustrazine has a certain inhibiting effect on the contraction of isolated trachea strips of guinea pigs caused by leukotriene C4, D4, histamine, prostaglandin F2 α and the like under the action of a respiratory system, is a non-competitive antagonist, but cannot resist the contraction of trachea caused by acetylcholine, the ligustrazine has an obvious inhibiting effect on elastase in vitro, has a prevention and treatment effect on an elastase emphysema model of guinea pigs, and the intravenous injection of 120mg/kg of the ligustrazine can prevent and protect rat experimental pulmonary edema caused by epinephrine, obviously improves the survival rate, improves the pathological change and also has a better prevention effect on oleic acid type respiratory distress syndrome.

6. After sodium taurocholate is used for inducing Acute Hemorrhagic Necrotizing Pancreatitis (AHNP) of rats, the ligusticum wallichii can increase relative pancreatic blood flow and perfusion amount, alleviate pathological morphological injury of pancreas, stabilize TxA2/PGI2 at a normal level, reduce the content of serum lipid peroxide, inhibit elastase, improve the survival rate of animals, and effectively prevent pancreatitis.

In the canine acute hemorrhagic necrotizing pancreatitis model prepared by injecting the bile of a dog by pancreatic duct pressurization, the ligustrazine can reduce the blood viscosity, the range of blood amylase and pancreatic necrosis and prevent the development of lesions, and the ligustrazine can also effectively prevent (or reduce the toxicity of rat islet β caused by cyclosporine by reducing the ratio of thromboxane B2 to 6-keto-prostaglandin F1 α.

7. The ligustrazine with the anti-tumor and anti-radiation effects can obviously inhibit the artificial lung metastasis of B16-F10 melanoma under the condition of daily dosage of 20mg/kg and 18 days of administration. The ligustrazine can enhance the activity of natural killer cells (NK) of spleen of normal and tumor-bearing mice and antagonize the inhibition of cyclophosphamide on the NK activity. 1 time of administration of the ligusticum wallichii has certain anti-metastasis effect on lung metastasis of hepatoma cells of mice, but the effect is not constant. Ligustrazine can enhance cytotoxic effect of anticancer drug adriamycin, and partially correct drug resistance of cancer cells. Ligustrazine can inhibit growth and proliferation of fiber cells, and reduce proliferation of fiber tissue caused by radiation. The ligusticum wallichii and the ligusticum wallichii probably reduce the surface activity of tumor cells, so that the ligusticum wallichii and the ligusticum wallichii are not easy to adhere to each other and agglomerate, are easy to be singly killed in blood flow, change the high blood coagulation state of a cancer patient, inhibit the metastasis of the cancer cells, improve the sensitivity of tumors to radiation, reduce radiation injury and have higher clinical application value.

8. Other methanol and hexane extracts of ligusticum wallichii can improve or partially improve the memory acquisition disorder caused by scopoletin carbon, but has no obvious effect on the memory consolidation disorder caused by sodium nitrite and the memory reproduction disorder caused by 40% ethanol, the water extract and the alcohol extract of ligusticum wallichii have obvious inhibition effect on the acetic acid writhing reaction of mice, the water extract of ligusticum wallichii can obviously improve the contraction amplitude of isolated uteri of rats, but has no obvious effect on the contraction frequency, the alcohol extract can increase the contraction amplitude, the frequency is reduced, the content of prostaglandin E2(PGE2) in ovaries can be reduced, in pseudopregnant rats, the ligusticum wallichii can reduce the content of progesterone in blood, inhibit the specific binding capacity of an ovary hCG/L H receptor and improve the specific binding capacity of a uterine progesterone receptor, and the ligustrazine can also prevent and treat the renal toxicity of gentamycin.

Scutellaria baicalensis:

[ pharmacological actions ]

1. Antibacterial, antiviral, antifungal: the decoction has inhibitory effect on various cocci, bacilli, drug-resistant Staphylococcus aureus, influenza virus, and dermatophytes.

2. And (3) clearing heat: the decoction and baicalin have antipyretic effect on experimental fever rabbit.

3. The functions of reducing blood pressure and promoting urination: baicalin is injected into anesthetized dogs, and has obvious blood pressure lowering and diuretic effects.

4. Anti-inflammatory and anti-allergic: animal experiment of baicalin and baicalein can inhibit exudation of allergic inflammation, reduce capillary permeability, and has antihistaminic and acetylcholine resisting effects

Motherwort:

[ pharmacological actions ]

1. Effects on uterus: herba Leonuri decoction, ethanol extract and leonurine have exciting effect on isolated uterus of rabbit, cat, etc.

2. Effect on cardiovascular system: the motherwort herb can obviously increase the coronary flow and quite obviously slow down the heart rate of an isolated guinea pig heart by using isoproterenol to cause a myocardial ischemia model. The motherwort preparation for intravenous injection has the functions of obviously increasing coronary flow, reducing coronary resistance, slowing down heart rate and reducing output and left ventricle work of anesthetized dogs.

3. Platelet aggregation resistance and thrombosis resistance: in vitro experiments prove that the motherwort and the extract thereof have the function of antagonizing platelet aggregation of normal animals induced by ADP. In vivo experiments also prove that the motherwort can obviously reduce the total number of platelets in peripheral circulation and the platelets and aggregates thereof in alveolar wall capillary vessels. The motherwort herb has obvious dissolving effect on the red thrombus in the lung circulation of the rabbit.

In addition, herba Leonuri has the effect of enhancing cellular immunity.

Houttuynia cordata:

1. improving immunity

The houttuynia cordata can enhance the phagocytic capacity of WBC and improve serum properdin, and when the houttuynia cordata is used for treating chronic tracheitis, the synthesized houttuynin can obviously improve the phagocytic capacity of WBC of a patient on staphylococcus albus and obviously improve the serum properdin. The rabbit is injected intramuscularly with 8mg of houttuynine sodium bisulfite every day. After continuous administration for 3 days, properdin in serum is obviously increased, and the houttuynia cordata improves the immunity of the organism, and has important significance for treating infectious diseases.

2. Antibacterial effect

The houttuynia cordata is extracted into yellow oily matter, has inhibition effect on various microorganisms (especially yeast and mould), and has obvious inhibition effect on hemolytic streptococcus, staphylococcus aureus, influenza bacillus, catacoccus and pneumococcus. It also has effect on Escherichia coli, Bacillus dysenteriae, and Bacillus typhi, and the synthetic decanoyl acetaldehyde sodium bisulfite adduct is called synthetic houttuynin. The synthesized lauroyl acetaldehyde sodium bisulfite addition compound is called as new-color fishy grass element, and has obvious inhibiting effect on various bacteria in vitro and in vivo experiments: the MIC for staphylococcus aureus and penicillin-resistant bacteria is 62.5-80mcg/ml, and for influenza bacillus is 1.25 mg/ml. The concentration of the strain of Mycobacterium tuberculosis H37RY on the Pribeiz liquid medium was 16 mcg/ml. 25mcg/ml on modified Sutong semi-solid medium, and 12.5mcg/ml of houttuynia cordata potassium salt.

3. Antiviral action

Human embryonic kidney primary single-layer epithelial cell tissue culture is carried out, and the houttuynia cordata decoction (l: 10) has an inhibiting effect on influenza Asian A Jingke 68-1 strain and can delay the growth of the orphan virus ECHO 11. Zhuyu reports: extracting with ethanol to obtain several non-volatile oil fractions. The houttuynin III has preventive protection effect on influenza virus infected mice, has no obvious effect on EMC and HSV II, and has stronger antiviral effect on the synthesized houttuynin derivative. The houttuynia cordata extract (4g crude drug/ml) has obvious prevention and protection effects on mice infected by the influenza virus. But has no obvious protective effect on the infection of encephalomyocarditis virus and herpes virus II. And proves that the houttuynia cordata anti-influenza virus component is not in the volatile oil part but in the non-volatile matter.

4. Diuretic effect

The herba Houttuyniae extract can perfuse Bufo siccus kidney or frog web, dilate capillary vessel, increase blood flow and urine secretion, and promote urination. The action may be caused by organic matters, potassium only has the additional effect of increasing diuresis, and when the potassium is directly used, the activity of leptospira can be weakened, death and lysis can be realized, and the onset period of guinea pigs artificially infected with leptospira can also be delayed.

5. Radiation protection

Herba houttuyniae is the only Chinese medicinal material which can be durably regenerated at the explosion point of atomic bomb. The houttuynia cordata has the effects of resisting radiation and enhancing the immunity of the organism, has no toxic or side effect, and is not only suitable for flight personnel, but also suitable for personnel who are often close to a radiation source, such as X-ray machines and computer operators, and people who often watch television. The computer family must eat radiation-proof food.

6. Combined action with TMP

When the compound is matched with TMP, the P of the 0.75mg/ml houttuynia cordata group and the P of the 0.75mg/ml houttuynia cordata-7.5 mg/ml TMP group are compared (t is 5.6) to be less than 0.001, and the difference is very obvious. The P of the 0.75mg/ml houttuynine sodium bisulfite-7.5 mg/ml TMP compatible group is less than 0.01 compared with the 7.5mg/ml TMP group (t is 2.78), and the difference is obvious. The antibacterial effect of the combination of the two is better than that of the single use, and the two have synergistic action. 0.1ml/ml of houttuynia cordata volatile oil has no bacteriostatic action, and the P of a 0.1ml/ml houttuynia cordata volatile oil-7.5 mg/ml TMP compatible group and a 7.5mg/ml TMP group (t is 4.2) is less than 0.001, so that the houttuynia cordata volatile oil has a very remarkable antagonistic action, which indicates that the houttuynia cordata volatile oil can reduce the bacteriostatic action of the TMP.

7. Pathogenic microorganism action

The houttuynia cordata ethyl ether extract has obvious inhibition effect on the tubercle bacillus in vitro, and the oily matter extracted from the houttuynia cordata has inhibition effect on various microorganisms (particularly mould and yeast) and has obvious inhibition effect on the hemolytic streptococcus, staphylococcus aureus, influenza bacillus, catacoccus catarrhalis and pneumococcus; it also has inhibitory action on colibacillus, dysentery bacillus and typhoid bacillus, but it is also reported that the antibacterial action of houttuynia decoction is not very obvious.

The sodium bisulfite addition product of decanoyl acetaldehyde artificially synthesized in China is called synthetic houttuynin, has obvious bacteriostatic action on various gram positive and negative bacteria in vitro, is sensitive to staphylococcus aureus and penicillin-resistant strains thereof, streptococcus pneumoniae, streptococcus A and influenza bacillus, has less toxicity to staphylococcus, pseudomonas aeruginosa and dysentery bacillus, and can obviously prolong the survival time of the houttuynin for tubercle bacillus infection of mice The trichophyton imbricatum, microsporidia gypseum, microsporidia ferrugineum, scyllo tinea and the like also have obvious inhibiting effect.

The houttuynia cordata decoction has strong inhibiting effect on leptospira in test tube, and can weaken, die and crack leptospira under direct action, and delay the onset period of guinea pigs infected with leptospira artificially.

Human embryonic kidney primary single-layer epithelial cell tissue culture is adopted, and the heartleaf houttuynia herb decoction (1:10) has an inhibiting effect on influenza Asian A Jingke 68-1 strain and can delay the growth of an orphan virus (ECHO 11). The experiment proves that: the houttuynia cordata extract has obvious prevention and protection effects on mice infected by influenza virus, and has obvious effects on both gastric lavage and nasal drip administration; but has no obvious protective effect on the infection of encephalomyocarditis virus and herpes virus type II.

8. Action on the immune System

The houttuynia cordata decoction can obviously promote the ability of human peripheral blood leukocytes to phagocytose staphylococcus aureus in vitro, and the synthesized houttuynine sodium bisulfite can improve the phagocytic function of the leukocytes of patients with chronic tracheitis and improve the serum properdin level of rabbits and patients.

9. Anti-tumor effect

The inhibitory effect of new houttuynin on ehrlich ascites carcinoma may be related to the increase of cAMP levels in cancer cells experiments show that: when different doses of the new houttuynin are injected into the abdominal cavity of the mouse at different time, the total number of cancer cells, the division index of the cancer cells and the abdominal water volume are all obviously reduced, and the cAMP level in the cancer cells is increased.

10. Anti-inflammatory action

The houttuynia cordata decoction has a remarkable anti-inflammatory effect on the formaldehyde-induced foot swelling of rats and can also remarkably inhibit the thermal denaturation of human gamma-globulin in the presence of Cu + +; houttuynin can obviously inhibit mouse ear swelling and skin capillary permeability increase caused by croton oil and xylene, and also has obvious inhibition effect on dye exudation of abdominal cavity capillary caused by HCA.

11. Other effects

The houttuyniA cordatA oil can obviously antagonize the effect of slow reaction substances (SRS-A) on isolated guineA pig ileum, can obviously inhibit the allergic contraction of the isolated guineA pig ileum, antagonizes the contraction of histamine and acetylcholine on the guineA pig ileum, and has obvious protective effect on the guineA pig allergic asthmA.

The houttuynia cordata water solution is injected subcutaneously to have mild sedative and anti-convulsion effects, can inhibit spontaneous movement of mice, prolong the sleep time of the cyclohexarbital sodium, and resist convulsion caused by strychnine; the heartleaf houttuynia herb decoction can be used for intravenous injection of 20-40 mg/kg to dogs to reduce the blood pressure by 40-50 mmHg (5.32-6.65 kPa), and can inhibit isolated toad hearts; the intraperitoneal injection has the functions of relieving cough of mice caused by ammonia water spray, but does not have the functions of eliminating phlegm and relieving asthma.

12. Toxicity

The toxicity of the houttuynia cordata is very low, L D50 injected subcutaneously into mice is 1.6 +/-0.081 g/kg, 1.5mg of houttuynine sodium bisulfite (which is about 200 times of the injection dose of a human body) is injected intravenously into the mice with the body weight of 17-20g, no death phenomenon is observed after 1 week, 90% of body weight is increased after dissection, no pathological changes occur after dissection, 38-47mg/kg of intravenous drip of dogs cannot cause death, the death can be caused when the injection dose is increased to 61-64mg/kg, severe hemorrhage and thrombus can be seen in dissected lungs, 80-160mg/kg of dogs are injected subcutaneously, 1mo is continuously injected, a large amount of salivation can be seen, vomiting often occurs in early stage, appetite, hemogram, liver and kidney functions and the like are not obviously affected, the stomach is perfused into dogs, 80-160mg/kg of dogs every day, 1 month is continuously observed, a large amount of salivation can be seen, vomiting often occurs in early stage, the southern China, the mouse is provided with the evaluation objective mouse body weight of the method of the injection of the mouse, the mouse is divided into a mouse, a mouse phagocytosis test result that the injection of the mouse is injected immunotoxicity test, a mouse is injected with an immunotoxicity test result that the mouse is equivalent to a mouse, a mouse injection vaccine, a mouse is injected with a mouse, a mouse is injected immunotoxicity test result that the mouse is equivalent to a mouse, a mouse is injected with a mouse phagocytosis test result that the mouse is equivalent to a mouse, a mouse is equivalent to a mouse phagocytosis test result that the mouse phagocytosis test result of a mouse is equivalent to a mouse phagocytosis test result of a mouse, a mouse phagocytosis test result of a mouse is equivalent to a mouse, a mouse.

Herba Patriniae: herba Patriniae has antibacterial and antiviral effects. Herba Patriniae has effects of protecting liver and promoting bile flow. Herba Patriniae has tranquilizing effect, and its effective component is saponin. Herba Patriniae has anti-tumor effect.

Borneol:

is easy to penetrate blood brain barrier. Borneol easily penetrates the blood brain barrier. Research shows that borneol can relax the intercellular locking small band of blood brain barrier obviously to speed the intercellular transfer of matter.

Promoting drug absorption.

① the product is effective in promoting transdermal absorption of topical corticoids and diclofenac sodium.

② can promote the penetration of medicine through cornea, and improve the bioavailability of medicine for eye.

③ it can promote the penetration of medicine through nasal mucosa, increase the absorption rate of medicine into brain, and increase the absorption amount of medicine in brain tissue, and is a quick-acting way for treating ischemic cerebrovascular insufficiency in acute stage.

Can be used for treating ischemia and injury of circulatory system. Borneolum Syntheticum is beneficial for preventing and treating coronary spasm, and can relieve myocardial injury caused by ischemia. The experiment shows that: the borneol has similar effect to that of a storax pill for coronary heart disease on an anaesthetized dog with acute myocardial infarction, and can increase blood flow of coronary sinus, slow down heart rate and reduce myocardial oxygen consumption. Has bidirectional regulating and protecting effects on central nervous system. One is the bi-directional regulation of the center. Borneol has two-way regulation effect on central nerve excitability, and has the functions of tranquilizing and allaying excitement and restoring consciousness. The second is the protection effect on the central nervous system. The borneol has protective effect on the brain, is beneficial to the recovery of encephaledema, protects the subsequent injury caused by cerebral ischemia and improves the damaged and awakening capability. In addition, borneol also has the function of promoting the division of glial cells. Antibacterial, antiinflammatory, and analgesic effects. The natural borneol can obviously inhibit the increase of the permeability of capillary vessels in the abdominal cavity of a mouse caused by acetic acid and has an anti-inflammatory effect; can obviously prolong the pain response time and the pain response of the mouse caused by thermal stimulation, and has the function of analgesia; the in vitro direct antiviral test shows that the compound has the function of inhibiting influenza virus.

Has antifertility effect. Borneol can cause the abortion of mice with middle and late pregnancy, the pregnancy termination rates are respectively 100% and 91%, but the effect on early pregnancy is not obvious. Promoting wound healing. Borneol can increase granulation tissue structure and epidermal cell regeneration, repair skin accessory organs and has stronger wound healing effect.

Astragalus polysaccharide:

1. action on the immune System

1.1 to notSpecific immune functionThe Astragalus Polysaccharide (APS) can obviously enhance the nonspecific immunity function and the humoral immunity function, so thatWhite mouseThe percentage and index of sheep red blood cells phagocytized are obviously enhanced, the formation of serum hemolysin is promoted, the hemolytic function and the obvious carbon profile effect of plaque forming cells are improved, and the weight of the spleen is obviously increased. Further separation of Astragalus polysaccharides to give 3 monomeric polysaccharides 123, and experiments conducted separately, showed that polysaccharide 1 increased spleen weight and cell number, but inhibitedSpleen cellImmune response to sheep red blood cells. 2 is similar to 1 but weaker, polysaccharide 3 has no effect. The astragalosides can promote lymph node B cell proliferation and differentiationPlasma cellsAntibody formation. The astragalus can promote the formation of immune specific rosettes of mouse lymphocytes to sheep blood cells. Astragalus polysaccharides can significantly enhance phagocytic luminous intensity of macrophage and inhibitPGE2But further promotes the release of TNF.Cyclooxygenase enzymeSuppression ofIbuprofenThe release of PGE2 and TNF is obviously inhibited, and the phagocytic function is not obviously influenced. Thus, can suggest an immunostimulant andcyclooxygenase inhibitorsThe composition is expected to become a new scheme for treating the wound infection by medicaments.

1.2 action on humoral immunity

Radix astragali has obvious effect of promoting the antibody generation function of normal organism. The astragalus root can enhance the humoral immunitySingle core macro Phagocytic cellPhagocytic activity ofSomatic cell,Natural killer cellRelease of immunologically active substances, inductionInterferon,InterleukinsEtc. exhibit various physiological activities. One of the antiviral principles of the traditional Chinese medicine composition is that the capacity of inducing interferon by leukocytes of a patient is improved, and IgE3 is obviously increased after a normal person takes the astragalus whole plant extract tablet. Radix astragali can promote phagocytic function of macrophageB cellAnd inhibits total complement activity. Inducing interleukin production, promoting formation of immunospecific rosettes of mouse lymphocyte on sheep blood cells, and inducing immunosuppressive agentHypoimmunityHas obvious protective effect and bidirectional effectImmunomodulator. Astragalus polysaccharides are substances with strong immunocompetence in Astragalus and can enhance the phagocytic function of phagocyte, and are derived from the weight of spleen and thymus, hemolysin,hemagglutinin (HA)And the total number of splenocytes and the plaque forming cells are determined, the astragalus polysaccharide and the hedysarum polysaccharide can be used for treating the cyclophosphamide or the prednisoloneImmunosuppressive effectHas complete and partial antagonistic effect.

1.3 action on cellular immunity Astragalus can promote the immune function of somatic cells.

Its effect on enhancing the immune function of human blood lymphocytes may be due in part to a reduction in the activity of suppressor T cells. Astragalus polysaccharides can be used for regulating content and promotingPhosphatidylinositolMetabolism and thus increased post-traumatic activationLymphoid tissue CellThe gene transcription expression of I L-2 mRNA and I L-2 RmRNA is one of the mechanisms of astragalus polysaccharide to correct cellular immune hypofunction after woundT cellsAnd the regulation of the cytokines secreted by them may be related to their regulationSubclass IgGIs relevant to the generation of (2).

1.4 Effect on Natural killer cells

Radix astragali can protectTarget cellResist T cell activity, but not to the extent that it promotes T cell activity. It has effects in increasing NK cell activity by inducing lymphopoiesisThe cells produce type II interferon mediators. Therefore, NK cells are considered to be precursor cells of T cells, and the influence of astragalus on the NK cells is consistent with the activation effect of astragalus on the T cells.

1.5 Effect on induced Interferon

Astragalus has obvious stimulation effect on interferon system, including self-induction, promotion of induction and activity play 3 aspects, astragalus has certain antitumor effect, astragalus polysaccharide (5mg/kg) is similar to the antitumor effect of I L-2/L AK, and has obvious enhancement effect on the antitumor effect of I L-2/L AK.

2. Influence on the metabolism of the body

2.1 Effect on cellular metabolism

By observing human fetal kidney cells, human fetal lungDiploid cellAnd mouse kidney cells in the form of cells containing astragalus rootNutrient solutionThe astragalus root can enhance the physiological metabolism of cells during the growth. After the water decoction of the mouse and the normal person take the astragalus dry extract tablet, the CAMP content of the blood plasma is obviously improved. Mouse SCAstragalus root injectionThe total number of the white blood cells and the number of the multinuclear white blood cells can be obviously increased. Radix astragali can also promote various diseasesProduction of blood cellsDevelopment and maturation process, and promoting hematopoietic function of bone marrow. For in vitro culture of hepatocyte and radix astragali, RNA can be promotedProtein synthesisIt is suggested that it can prolong cell life, enhance cell metabolism and delay aging.

2.2 Effect on nucleic acid metabolism

The degree of inhibition of the activity of free RN-ase by Astragalus Polysaccharides (APS) was that kidney < liver < lung < spleen, which was explained by the relative rate of increase of the equilibrium response, the effect of APS was significant in low RI tissues. The astragalus root has the function of inhibiting the RNA metabolism of human lung diploid cells, and the astragalus root decoction can obviously promote the synthesis of bone marrow hematopoietic cell DNA and accelerate the process of karyocyte division. The astragaloside can obviously increase the DNA content of the regenerated liver, and the astragaloside has no obvious influence on the metabolism of the DNA.

2.3 Effect on the Effect of internal Cyclic nucleotides

The astragalus decoction can obviously increase the content of internal cyclic nucleotides (cAMP and Cgmp) in the plasma and tissues of mice, and the influence of the astragalus decoction on each organ is different; administration paircAMP elevation, cGMP decline; the liver is the opposite; but increased in the spleen. Further experiments showed that the effect of Astragalus on cAMP is due to its inhibitionCyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE).

2.4 Effect on protein and other metabolism

The astragalus root decoction is continuously infused into the stomach of a mouse for 10 days, and H-supplement can be obviously increasedLeucineThe rate of incorporation of serum and liver proteins, but no influence on the content of proteins, namely, astragalus can promote the serum and protein turnover of mice, and the polysaccharide in the astragalus is considered to be an effective component for promoting the protein turnover. The astragaloside 100g/kg has similar effect when administered by intragastric administration. The astragalus has a tendency of increasing the blood sugar level of the animals with insulin hypoglycemia, but the increase range is small.

3. Action on the cardiovascular System

3.1 action on the Heart

Astragalus root waterThe decoction has no obvious effect on isolated frog heart, and the alcohol extract can enhance the isolated frog or toad heart contraction, obviously enlarge the amplitude, and inhibit the in case of large dose. Therefore, the astragaloside can realize the cardiotonic effect through NA and K-ATP enzyme. Astragalus has been reported to be capable of stimulating human myocardial cellsLactate dehydrogenaseAndsuccinate dehydrogenaseThe content is increased in different ways. The above suggests that Astragalus has calcium antagonistic action, can reduce the myocardial CA inflow caused by viral infection, possibly reduce the secondary CA injury of infected cells, and inhibit the replication of viral RNA in cells, showing that it is in the treatment of chronic hepatitis B virusViral myocarditisThe application value in clinical treatment. However, a single dose of astragalus membranaceus had no prophylactic effect on CVB3 myocarditis. Astragaloside has positive inotropic effect on cardiac muscle, andcardiac glycosidesThe quasi drugs are similar. Experiments prove that the total saponins of astragalus can obviously improve the heart contractility of the myocardial infarction dog, enhance the coronary flow and have the protection effect on the heart function. Research shows that the function of astragalus root in resisting oxygen free radical may be one of cardiac action mechanisms. The astragaloside IV injection is non-Digitalis purpurea (L.) MerrEffective inotropic drugs of the class.

3.2 Effect on blood vessels and blood pressure

Radix astragali has effects of dilating blood vessel and coronary artery.Therefore, it is considered that the hypotensive effect is a result of directly dilating peripheral blood vessels, and is independent of the heart andhistamineRelease or adrenergic receptor action is also irrelevant. The influence of the astragalus root on the blood pressure is the same as that of the central neuropeptide,renin-angiotensin-aldosterone system,CarnosineThe system of releasease-carnosine, hydroxyproline, etc. The hypotensive component of Astragalus has been considered to be an alkaline substance, but it was later discoveredAstragalus genusThe plant root contains aminobutyric acid, and the content of the aminobutyric acid is almost completely parallel to the strength of the antihypertensive effect, so the aminobutyric acid is considered as the antihypertensive active ingredient. In terms of vascular effects, aminobutyric acid does not fully represent astragalus. Radix astragali can promote the growth of radix astragali in different degreesVascular endothelial cellsMigration and proliferation are beneficial to promoting the angiogenesis process.Astragalus membranaceus (Fisch.) bgeSaponins such as astragaloside IIIIIIV, formononetin, calycosin, etcIsoflavonesCompounds, to hatchingDeformability of erythrocytesHas obvious improvement effect, which is probably the improvement of the astragalus membranaceusBlood circulation Rheology of liquidAn important mechanism of the index, an important link of the action of astragalus to the membrane of human erythrocyte, may beProtecting peopleThe red cell membrane is protected from free radical attack.

4. Effect on stress response

4.1Anti-fatigueFunction of

250mg/kg and 500mg/kg of astragalus polysaccharide are injected into the abdominal cavity of a normal mouseHydrocortisoneThe swimming time of the 'yang deficiency' mouse at normal temperature is obviously prolonged, and the weight of the adrenal gland of the mouse in a stress state is increased. Radix astragaliExtract liquidFor rats in swimming stress statePlasma cortisolThe content, the weight of the adrenal gland and the content of lipid vacuoles in adrenal cortex cells are all obviously improved. Two sidesCarotid arteryCaused by ligationCerebral hypoxiaAll have obvious antagonistic action, and can obviously prolong the survival time of mice.

4.2 Low-temperature and high-temperature resistance

250mg/kg and 500mg/kg of astragalus polysaccharide are injected in the abdominal cavity, so that the low-temperature resistant effect of a normal mouse, a hungry mouse and a mouse treated by hydrocortisone can be obviously enhanced, and the survival time is obviously prolonged; but has no obvious high temperature resistance. 5.4.3Radiation-resistant Shooting deviceActing on radix astragaliTotal FlavonoidsHas certain protective effect on the immune system damage caused by the radiation. The action mechanism of the composition may have antioxidant and free radical scavenging effects with radix astragali total flavone, so that immunocyte can be preventedLipid peroxidationWhile astragalus total flavonoids may also have the functions of changing the energy metabolism of immune cells and promoting the division of lymphocytes.

5. Has antiaging effect and can be taken for a long time

Radix astragali has certain significance in preventing senile arteriosclerosis and improving aging lung function. In vitro culture of human embryo lung diploidFibroblast cellThe cultured cells with 0.2% radix astragali extractive solution survive to 52 generations, and the cells of the group are agedOrganelleThe change is basically the same as the aging transformation ratio law of the control group cells, but the change degree is light, the change rate is relatively slow, particularly the change of the drug group cellsGolgi complexParticularly developed, although cells have senesced, they are not as senescing. Researches prove that the astragalus has good effect of prolonging life, and the astragalus is taken as an anti-aging and life-prolonging medicament, and is worthy of high importance and development.

6. Action on urinary system

Intravenous injection of radix astragali injection for treating rat diseasesNephropathy with minimal pathological changesOf modelsSerum albuminThe content of the organic acid is obviously increased,serum CholesterolObviously reduce and increase the blood transportation of glomerular capillary filamentsEdema of scrotumHas obvious effect of alleviating ascites, and the diet and mental state of the animals in the administration group are better than those in the control group; the astragalus can obviously reduce the amount of protein in urine; pathological observation also proves that the pathological changes of the astragalus group are reduced, and the repression effect on nephritis is probably related to the enhancement of metabolism and improvement of the whole body nutrition state of the astragalus. Astragalus root can relieve kidney diseases of mice with spontaneous lupus through immunoregulation.

7. Liver protection effect

Radix astragali has effects of protecting liver and preventing reduction of hepatic glycogen. Two astragalosides ASI and SK can resistD-galactoseAmines andacetaminophenCaused byLiver damageAstragaloside is an effective component of astragalus root for resisting hepatotoxic injury, and the mechanism of astragaloside is not only biological oxidation resistance but also combined with that of astragalus rootRegulation of metabolismNode (C)It is related. In addition, the research suggests that astragalus root has a certain effect on preventing hepatic fibrosis.

8. Action on the central nervous system

The mice are injected with astragalus root subcutaneously to maintain the sedative effect for hours. The mice drink 30% of astragalus root water decoction for 15 days, which has the function of strengthening the learning and memory of the mice, and the experiments show that the astragalus root is beneficial to the storage of the information of the brains of the mice

9. Action on smooth muscle

5 percent and 10 percent of astragalus decoction can obviously increase the tension of intestinal canals of in-vivo rabbits, slow the peristalsis and increase the amplitude; has inhibitory effect on isolated intestinal canal and uterus of rabbit. The astragalosides can reduce tension of guinea pig isolated ileum.

10. Hormone-like action

The astragalus lactone and the astragaloside in the astragalus extract have no obvious influence on the weight of rats and mice, the weight of levator ani muscles or kidneys and the like, and the situation shows that the astragalus lactone and the astragaloside have no obvious influence on the weight of rats and mice, and the weight of levator ani muscles or kidneysAssimilation of hormonesOr male hormone-like effects.

11. Antibacterial and antiviral effects

Astragalus polysaccharides pairTubercle bacillusThe infection has obvious antagonistic effect; other components such as amino acids, alkaloids, and flavones have been found to have significant resistance to follicular formationStomatitis (stomatitis)The role of the virus. Animal and cell transmission experiments show that the astragalus injection is used in the body of mouseEpidemic hemorrhagic feverAnd the infection process of virus (EHFV) has certain blocking effect. The astragalus root is used for treating dysentery bacillus, anthrax bacillus, alpha-blood-activating streptococcus,Streptococcus sanguisDiphtheria, pseudodiphtheria, diphtheria, diphth,Diplococcus pneumoniae、Golden yellow grape Staphylococcus aureus、Lemon colorStaphylococcus, Staphylococcus albus and Bacillus subtilis, etc. have antibacterial effects.

12. Anti-tumor effect

Animal experiments show that the astragalus polysaccharide has similar antitumor effect to I L-2/L AK and obvious enhancement effect on the antitumor effect of I L-2/L AKL AK cellsLethality against target cells. The two are combined to carry out dynamic cellular immune functionCan observe and indicate that the astragalus polysaccharide and the astragalus polysaccharide have the functions of resisting the reduction of the activity of NK cells in the spleen of a mouse and the generation capacity of I L-2, and indicate that the anti-tumor function of the astragalus polysaccharide is related to the function of enhancing the immunologic function of an organism, can improve the immunologic function reduction caused by the tumor of the organism, promote the activation of the immune cells to release endogenous factors, prevent peroxidation to further kill and inhibit tumor cells, and is used for treating tumorMarek's disease of chicken。

13. Effects on wound infection

The pharmacological experiment of astragalus polysaccharide on experimental mouse wounds shows that the astragalus polysaccharide can obviously enhance the phagocytic luminous intensity of macrophages, inhibit the release of PCE2 and further promote the release of TNF, and the immune activator astragalus polysaccharide and the cyclooxygenase inhibitor ibuprofen are combined together, so that the phagocytic luminous intensity of macrophages is enhanced, the secretion of PGE2 and TNF I L-1 is obviously inhibited, therefore, the combination of the immune activator and the cyclooxygenase inhibitor is expected to become a new scheme for the drug treatment of wound infection.

14. Protective action

Zhang YanThe results of the experiments show that astragalus polysaccharide has obvious protective effect on experimental liver injury and can obviously resist the mice caused by carbon tetrachloride and paracetamolSerum glutamic-pyruvic transaminaseAnd the protective effect on the pathological tissue change of the mice caused by the two drugs is obvious.

15. Regulating effect on blood sugar

APs have a bidirectional regulatory role. It can obviously reduce the blood sugar of a mouse with glucose load, can also obviously resist the blood sugar rising reaction of the mouse caused by epinephrine, and can also obviously resist the experimental hypoglycemia of the mouse caused by phenformin. But it has no significant effect on insulin hypoglycemia.

16. Antiviral effect of astragalus polysaccharide

Astragalus polysaccharides is a kind ofInterferon inducerIts antiviral principle: stimulating the functions of macrophage and T cell, increasing the number of E ring forming cells, inducing cytokine, promoting interleukin induction, and making animal produce endogenous interferon, so as to achieve the goal of resisting virus.

17. Antibacterial effect of Astragalus polysaccharides

The mechanism of action of the antibacterial agent is multifaceted, on the one hand, the direct killing and detoxifying action of the agent on bacteria and toxic products thereof. On the other hand, the other hand is more important by moving the machine bodyImmune defenseHas the functions of strengthening body resistance, eliminating pathogenic factors, inhibiting bacteria and killing bacteria. For Shigella shigella, Bacillus anthracis, type a, type b lysogenStreptococcus pneumoniaDiplococcus, staphylococcus aureus, escherichia coli and salmonella all have antibacterial effects.

18. Intestinal tract health-care function

The astragalus polysaccharides can increase the number of lactobacillus and bifidobacterium in the chicken intestinal tract, remarkably reduce the number of escherichia coli, effectively promote the proliferation of beneficial microorganisms in the intestinal tract and treat the intestinal tractHarmful bacteriaHas inhibitory effect. The metabolite is short chain fatty acid, and can reduce intestinal pH value. The low pH value can stimulate the intestinal peristalsis on one hand, thereby reducing the number of pathogenic bacteria, and the acidic environment is favorable for the other handLactic acid bacteriaAnd Bifidobacterium and the likeBeneficial bacteriumThe beneficial bacteria can generate metabolites with antibacterial activity such as hydrogen peroxide, organic acid and the like in the proliferation process, and can inhibit the survival of pathogenic harmful bacteria and exogenous pathogenic bacteria.

The present invention is further described below in conjunction with the experimental results.

10 cases of pigs in a farm of Zhengzhou city are selected, and the treatment results are compared by adopting the prescription and oxytetracycline tablets (0.05g) produced by commercial product Lizehongsheng pharmaceutical industry Limited.

Clinically, it can be divided into acute and chronic casesChronic endometritis。

(1)Acute endometritisObvious general symptoms, high body temperature of the sow, lassitude, anorexia or abominability, frequent liability, white mucus or foul red brown mucus flowing out of the vagina or foul red brown mucus flowing out of the vagina especially when the sow is just lying downPurulent nature Secretion materialThe secretion sticks to the root of the tail and smells bad. Sometimes the sow has abdominal pain symptoms. Acute diseaseMetritis of uterusIt is usually produced after parturition and abortion. (2) Chronic endometritis is mostly transformed from the untimely treatment of acute endometritis. The general symptoms of sick pigs are not obvious.The sick pig may periodically drain a small amount of turbid mucus from the vagina. Sows often delay oestrus or are in abnormal oestrus, and even if oestrus can be regularly developed, they are frequently infertile. And (3) curing: the symptoms are obviously improved or disappeared. The method has the following advantages: the symptoms are alleviated; and (4) invalidation: the symptoms did not improve significantly or did not improve.

Experimental groups: directly inserted into uterus of animals, 1 tablet at a time, 2 times a day.

Control group: directly inserted into uterus of animals, 16 tablets at a time, 2 times a day.

The experimental results are as follows:

accelerated stability investigation is carried out according to the requirement of the appendix of the first edition of the pharmacopoeia of the people's republic of China 2015, the initial detection result and the stage detection result are recorded, and the test results are shown in the table.

The above description is only for the purpose of illustrating the present invention and the appended claims are not to be construed as limiting the scope of the invention, which is intended to cover all modifications, equivalents and improvements that are within the spirit and scope of the invention as defined by the appended claims.

Claims (10)

1. The drug for treating animal metritis containing doxycycline hydrochloride is characterized by comprising 2.4-4 kg of doxycycline hydrochloride, 0.6-1.0 kg of lactic acid TMP, 1.5-2.5 kg of houttuynia cordata extract, 0.6-1.0 kg of Chinese angelica extract, 1.5-2.5 kg of patrinia herb extract, 1.5-2.5 kg of astragalus polysaccharide, 1.2-2.0 kg of scutellaria baicalensis extract, 10-14 kg of tartaric acid, 1.2-2.4 kg of sodium dodecyl sulfate, 8-12 kg of lactose, 12-20 kg of corn starch, 4kg of absolute ethyl alcohol, 22-0 kg of sodium bicarbonate mixture, 0.8-1.2 kg of magnesium stearate mixture and 2.4kg of carboxymethyl starch sodium by mass.

2. The drug containing doxycycline hyclate for treating metritis of an animal according to claim 1, wherein the drug containing doxycycline hyclate for treating metritis of an animal consists of 3.2kg of doxycycline hyclate, 0.8kg of lactic acid TMP0.8kg, 2kg of houttuynia cordata extract, 0.8kg of angelica sinensis extract, 2kg of patrinia scabiosaefolia link extract, 2kg of astragalus polysaccharide, 1.6kg of scutellaria baicalensis extract, 12kg of tartaric acid, 2.4kg of sodium lauryl sulfate, 10kg of lactose, 16kg of corn starch, 4kg of absolute ethyl alcohol, 24.15kg of sodium bicarbonate mixture, 1.020kg of magnesium stearate mixture and 2.4kg of carboxymethyl starch sodium;

3.2kg of doxycycline hydrochloride, 0.8kg of lactic acid TMP0.8kg, 2kg of houttuynia cordata extract, 0.8kg of Chinese angelica extract, 2kg of patrinia herb extract, 2kg of astragalus polysaccharide, 1.6kg of scutellaria baicalensis extract, 12kg of tartaric acid, 2.4kg of sodium dodecyl sulfate, 10kg of lactose and 16kg of corn starch, mixing for 30min, and granulating with 60% ethanol of 14 meshes.

3. The doxycycline hyclate-containing medicament for treating metritis in an animal according to claim 2, wherein the anhydrous ethanol is used in a reactor for preparing 60% ethanol.

4. The doxycycline hyclate-containing medicament for treating metritis in an animal according to claim 2, wherein the mixture of sodium bicarbonate consists of 20kg of sodium bicarbonate, 2kg of motherwort herb extract, 2kg of ligusticum wallichii extract, 2kg of absolute ethanol and PVPK300.15kg for preparing a binder; the above components except PVPK30 for preparing adhesive are mixed for 30min and separately granulated into granules of 14 meshes.

5. The doxycycline hyclate-containing medicament for treating metritis in an animal according to claim 4, wherein the K30 is dissolved in 75% ethanol, and the 75% ethanol is prepared from absolute ethanol;

the magnesium stearate mixture consists of 0.9kg of magnesium stearate and 120g of borneol, and the borneol and the magnesium stearate are crushed together, dried and then added externally.

6. A method for preparing the medicament containing doxycycline hydrochloride for treating metritis of an animal according to any one of claims 1 to 5, wherein the method for preparing the medicament containing doxycycline hydrochloride for treating metritis of an animal comprises the following steps:

step one, drying the granulated acid-base granules in an oven at the temperature of 60-65 ℃ for 3-5 h; controlling the moisture of the granules to be 3-4%, and finishing the granules with 12 meshes;

and step two, adding the acid-base granules together with the additional auxiliary materials of magnesium stearate, borneol and carboxymethyl starch sodium, mixing for 30min by using a two-dimensional mixer, and tabletting after the semi-finished product is qualified.

7. The method of claim 6, wherein the compressed tablet is prepared by: 20 g/tablet.

8. A medicament for treating metritis in a pig prepared by the medicament containing doxycycline hydrochloride for treating metritis in an animal according to claims 1 to 6.

9. A medicament for treating metritis in a cow prepared by the medicament containing doxycycline hydrochloride for treating metritis in an animal according to claims 1-6.

10. A medicament containing doxycycline hydrochloride for treating metritis of an animal prepared according to claims 1-6.

Images