CN111053807A - Traditional Chinese medicine preparation for preventing and treating dog threatened abortion and preparation method thereof - Google Patents
Traditional Chinese medicine preparation for preventing and treating dog threatened abortion and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a traditional Chinese medicine preparation for preventing and treating dog threatened abortion, which is prepared from the following traditional Chinese medicine raw materials in parts by weight: 5-8 parts of fried scutellaria baicalensis, 5-10 parts of fried bighead atractylodes rhizome, 5-10 parts of astragalus membranaceus, 5-10 parts of eucommia ulmoides, 5-10 parts of codonopsis pilosula, 5-8 parts of angelica sinensis and 3-5 parts of liquorice. The invention also discloses a preparation method of the composition. The traditional Chinese medicine preparation can obviously improve the child production rate, has definite curative effect and controllable quality, and fills the blank of the traditional Chinese medicine market for miscarriage prevention and miscarriage prevention in China.
Description
Technical Field
The invention relates to a traditional Chinese medicine preparation for dogs, in particular to a traditional Chinese medicine preparation for preventing and treating dog threatened abortion and a preparation method thereof.
Background
Various adverse factors during pregnancy of dogs may cause fetal development disturbance, fetal death and maternal physiological dysfunction, thereby causing abortion and even endangering maternal life. Therefore, the diagnosis and prevention of abortion and the research and development of related miscarriage prevention and treatment products have important scientific significance for guaranteeing the normal reproductive function of the dogs. In the research field, hormone therapy and antibiotic therapy are mainly used at home and abroad at present, but the hormone therapy has the problem of great side effect, and the antibiotic therapy has the problem of inaccurate curative effect.
Disclosure of Invention
The invention aims to solve the technical problem of providing a traditional Chinese medicine preparation for preventing and treating dog threatened abortion, which has the advantages of high birth child rate, exact curative effect, small toxic and side effects and controllable quality.
The invention also provides a preparation method of the traditional Chinese medicine preparation for preventing and treating dog threatened abortion.
In order to solve the problems, the traditional Chinese medicine preparation for preventing and treating dog threatened abortion is characterized in that: the preparation is prepared from the following traditional Chinese medicine raw materials in parts by weight: 5-8 parts of fried scutellaria baicalensis, 5-10 parts of fried bighead atractylodes rhizome, 5-10 parts of astragalus membranaceus, 5-10 parts of eucommia ulmoides, 5-10 parts of codonopsis pilosula, 5-8 parts of angelica sinensis and 3-5 parts of liquorice.
The preparation method of the traditional Chinese medicine preparation for preventing and treating dog threatened abortion comprises the following steps:
⑴ are weighed according to the mixture ratio;
⑵ mixing radix Scutellariae preparata, rhizoma Atractylodis Macrocephalae preparata, radix astragali, cortex Eucommiae, radix Codonopsis, radix Angelicae sinensis, and radix Glycyrrhizae, decocting in water, centrifuging, and filtering to obtain Chinese medicinal liquid;
⑶ concentrating the Chinese medicinal liquid at 60 deg.C to obtain fluid extract with relative density of 1.13-1.15;
⑷ adding wetting agent and adhesive into the fluid extract, granulating, and spray drying to obtain Chinese medicinal granule with water content of 2-4%, wherein the mass ratio of the fluid extract to the wetting agent is 1: 0.05-0.1, and the mass ratio of the fluid extract to the adhesive is 1: 0.1-0.3;
⑸, adding a lubricant after the traditional Chinese medicine particles are qualified by sampling inspection, mixing and tabletting to obtain the tablet with the porosity of 2-10%, wherein the mass ratio of the traditional Chinese medicine particles to the lubricant is 1: 0.08-0.12.
The condition of water decoction in the step ⑵ is that the ratio of the raw materials to the liquid is 1: 8-12, the decocting times are 2 times, and each time is 20 min.
The centrifugal filtration in the step ⑵ is performed at a speed of 1000-2000 r/min for 5-10 min.
The spray drying condition in the step ⑷ is that the inlet temperature of a spray drying chamber is 180-220 ℃, the drying temperature is 60-80 ℃, and the drying time is 5 s.
The wetting agent in the step ⑷ is absolute ethyl alcohol.
The binder in step ⑷ is dextrin.
The lubricant in step ⑸ is magnesium stearate.
The scutellaria baicalensis in the formula has the effects of clearing heat and drying dampness, purging fire and detoxifying, stopping bleeding and preventing miscarriage, and is a monarch drug; the bighead atractylodes rhizome has the effects of strengthening spleen and tonifying qi, eliminating dampness and promoting diuresis, arresting sweating and preventing miscarriage and is a ministerial drug; the astragalus has the effects of tonifying qi, strengthening exterior, inducing diuresis, removing edema, expelling toxin, expelling pus, promoting granulation and the like, and is used as a ministerial drug; the eucommia bark has the functions of tonifying liver and kidney, strengthening bones and muscles and preventing miscarriage, is a traditional miscarriage prevention medicament and is a ministerial medicament; the codonopsis pilosula has the effects of strengthening spleen, tonifying lung, nourishing blood and promoting the production of body fluid, has good effect on threatened abortion caused by deficiency of qi and blood, and is an adjuvant drug; the angelica has the functions of enriching and activating blood, regulating menstruation and relieving pain, and relaxing bowel, has good effect on threatened abortion caused by imbalance of qi and blood, and is used as a guiding drug; licorice root, radix Glycyrrhizae has the effects of tonifying the spleen, replenishing qi, and harmonizing the spleen and stomach, and is used as a guiding drug.
The functional indications are as follows: has effects of invigorating qi, invigorating spleen, nourishing blood, preventing miscarriage, and improving fetal irritability, and can be used for preventing and treating threatened abortion of dog in early gestation.
The usage and dosage are as follows: taking tablets as an example, the oral administration is carried out 3 to 5 tablets at a time and 1 time a day.
Compared with the prior art, the invention has the following advantages:
1. the invention fully utilizes the abundant plant medicine resources and the traditional fetus protection prescription in China, and overcomes the defects of great toxic and side effects, common curative effect and the like of hormone therapy and antibiotic therapy.
2. Pharmacodynamic experiments:
[ acute toxicity test ]
The safety of the traditional Chinese medicine preparation is investigated by researching the acute toxic effect of the traditional Chinese medicine preparation on mice. The pre-test can not obtain the death dose of the mice caused by one-time gavage of the traditional Chinese medicine preparation solution, so that LD can not be measured50. In the official test, the mice were observed for toxicity and death by oral drenching of the solution of the present invention using the method of measuring the maximum tolerance per day (see Table 1). As a result, the mice survived after 7 days of the experiment, the weight and the mental state of the mice were compared with those of the control group, no significant difference exists, and no pathological changes exist in the main organs after the mice are dissected. The results show that the oral administration of the traditional Chinese medicine preparation of the invention by mice is safe.
TABLE 1 Pre-test treatment method and test results
[ Long-term toxicity test ]
80 Wistar-line rats are randomly divided into 4 groups, each group comprises 20 rats, and the female and male rats are respectively a high-dose group, a medium-dose group and a low-dose group of the traditional Chinese medicine solution and a blank control group. The rats are administrated with 12g/kg, 6g/kg and 3g/kg of the traditional Chinese medicine preparation solution (the administration dosage is about equal to 37.62g/kg, 18.81g/kg and 9.41g/kg of body weight of the raw medicinal material) in the high, medium and low dose groups, and the administration is carried out once a day for 30 days continuously; the blank control group was infused with equal doses of normal saline. During the experiment, the rats in each group were observed for mental, behavioral, food intake, stool and death. Weight changes were weighed before dosing, every 10 days during dosing, and 15 days after drug withdrawal. On each of the 30 th and 45 th days of the test period, 10 rats were sacrificed and hematology, blood biochemistry, and organ index measurements were performed. As shown in tables 2, 3 and 4, the test results showed that no significant drug-induced toxicity was observed in the test group compared to the control group. The results show that the solution of the traditional Chinese medicine preparation is nontoxic when being taken at a larger dose for a longer period of time, and the traditional Chinese medicine preparation is safe in actual use.
TABLE 2 hematological indexes of each group of 30 days after administration and 15 days after withdrawal of the Chinese medicinal preparation of the present invention: ()
TABLE 3 blood biochemical indicators of each group of 30 days after administration and 15 days after withdrawal of the Chinese medicinal preparation of the present invention: ()
TABLE 4 Effect of the inventive Chinese medicinal preparation on the coefficients of major organs: ()
[ fetus protection test ]
Animal grouping and administration
The rats are bred in a separated adaptive manner for more than one week, selectively matured rats are bred in cages at 1:1 after 19 o 'clock in the night, the fertilization condition of the rats is observed before 7 o' clock in the next morning, and female rats with vaginal embolus are recorded as the 0 th day of pregnancy. Pregnant rats were randomly divided into a (normal pregnancy group), B (traditional Chinese medicine low dose group), C (traditional Chinese medicine medium dose group), D (traditional Chinese medicine high dose group), E (progesterone group), and F (threatened abortion model group), 10 rats were in each group, and there was no significant difference in body weight between the groups. On day 7 of pregnancy, B, C, D, E, F groups were gavaged with mifepristone 8.3mg/kg and misoprostol 100g/kg, respectively, to create a model of threatened abortion. Placing a small cotton ball in the vagina of a female mouse, and detecting that BLD (occult blood) in the cotton ball shows positive by occult blood, namely that the modeling is successful.
A first group: 10 rats were administered with physiological saline continuously on the first day of pregnancy at the same dose as the administration group;
second group: 10 rats were drenched with compound Chinese medicine continuously from the first day of pregnancy, 3g/kg/d, and on the 7 th day, 8.3mg/kg mifepristone and 100g/kg misoprostol were drenched;
third group: 10 rats were drenched with compound Chinese medicine continuously from the first day of pregnancy, 6g/kg/d, and on the 7 th day, 8.3mg/kg mifepristone and 100g/kg misoprostol;
and a fourth group: 10 rats were drenched with compound Chinese medicine continuously from the first day of pregnancy at 12g/kg/d, and on the 7 th day, with mifepristone 8.3mg/kg and misoprostol 100 g/kg;
and a fifth group: 10 rats were drenched continuously with equivalent dose of progesterone 2mg/kg/d from the first day of gestation and on day 7 with mifepristone 8.3mg/kg and misoprostol 100 g/kg;
a sixth group: 10 rats were administered with physiological saline continuously on the first day of pregnancy at the same dose as the administration group; on day 7, the stomach was gavaged with mifepristone 8.3mg/kg and misoprostol 100 g/kg.
Results of the fetus protection experiment
⑴ Effect of the Chinese medicinal preparation of the invention on the fetus-protecting rate of rats:
TABLE 5 pregnant rat body weight and survival rate
Note: is marked by difference (p<0.05) is extremely different (p<0.01) (same as in the following figure). The survival rate is the ratio of the number of the group born fetuses to the total number of the born fetuses.
As shown in table 5, the statistical results show that the weight change of the rats after model building in the normal pregnancy group is significantly higher than that in the threatened abortion group, (p <0.01), and the weight change of the rats in each other dose group is significantly lower than that in the normal pregnancy group (p < 0.05); the average number of the live fetuses of the model group is 1.37, which is obviously lower than that of other groups (P <0.05), after the high-dose traditional Chinese medicine is infused, the average number of the live fetuses is improved to 8.87, the difference with the average number of the live fetuses of the normal pregnancy group is not significant (P >0.05), and the average number of the live fetuses of the model group is obviously higher than that of other groups (P < 0.05).
⑵ Effect of the Chinese medicinal preparation of the invention on rat serum PPAP-A:
as shown in fig. 1, the statistical results show that the content of PAPP in the blank group is significantly different (p <0.05) compared with the traditional Chinese medicine high dose group, and the content of PAPP in the traditional Chinese medicine high dose group is significantly higher than that in the western medicine group (p <0.05), and is significantly higher than that in the group with threatened abortion (p < 0.01).
⑶ Effect of the Chinese medicinal preparation of the invention on rat serum PGF2 α:
as shown in fig. 2, the statistical results show that the content of PGF2 α in the blank group is significantly different (p <0.01) compared with the content of PGF2 α in the traditional Chinese medicine low dose group, and is also the same as the content of PGF2 α in the traditional Chinese medicine medium dose group (p <0.01), and at the same time, the content of PGF2 α in the traditional Chinese medicine low dose group is significantly different (p <0.01) from the group of threatened abortion, and the relationship of this significant difference is also shown between the traditional Chinese medicine high dose group and the western medicine group (p <0.01), while the content of PGF2 α in the traditional Chinese medicine low dose group is significantly higher than the traditional Chinese medicine medium dose.
⑷ Effect of the Chinese medicinal preparation of the invention on rat uterine tissue:
as shown in figure 3, the model group with 200 times of under-lens observation has obvious bleeding phenomenon on the uterine mucosa epithelium, the model group with 400 times of under-lens observation has the neutrophil in the inherent layer of the uterine mucosa and the embryo blood vessel, and the proportion of the neutrophil in the model group is obviously higher than that in other groups. Compared with the model group, the progesterone group has obviously reduced bleeding amount, but a large amount of white blood cells still exist; compared with the model group, the traditional Chinese medicine has the advantages that the amount of bleeding and the number of neutrophils are obviously reduced. The result shows that the abortion medicine can cause inflammatory reaction of different degrees of the uterus and embryo of a rat, so that the neutrophilic granulocytes of local tissues are increased, and the bleeding of local mucous membrane can be seen in the uterine cavity; the traditional Chinese medicine preparation can obviously reduce the amount of bleeding and neutrophils and reduce the uterine inflammatory reaction.
In conclusion, after the Wistar rat with the threatened abortion model is infused with the traditional Chinese medicine preparation, the level of the pregnancy protein in the serum of the rat can be increased, and the level of PGF2 α can be reduced.
The experimental results of different groups of Wistar rats with threatened abortion models are analyzed and compared, the difference has statistical significance, and the traditional Chinese medicine preparation has the function of preventing miscarriage of the Wistar rats with threatened abortion modeled by mifepristone and misoprostol.
3. The traditional Chinese medicine preparation can obviously improve the child production rate, has definite curative effect and controllable quality, and fills the blank of the traditional Chinese medicine market for miscarriage prevention and miscarriage prevention in China.
Drawings
The following describes embodiments of the present invention in further detail with reference to the accompanying drawings.
FIG. 1 is a graph showing the effect of the present invention on rat serum PAPP.
FIG. 2 is a graph showing the effect of the inventive pharmaceutical formulation on rat serum PGF2 α.
FIG. 3 is a section of rat uterus (embryo) of the present invention. Wherein: the uterus mucosa epithelium (H.E.200 x) in the group of normal pregnancy, the uterus mucosa epithelium (H.E.200 x) in the group of model B, the uterus mucosa epithelium (H.E.200 x) in the group of model C, the embryo blood vessel (H.E.400 x) in the group of normal pregnancy, the embryo blood vessel (H.E.400 x) in the group of model E, the embryo blood vessel (H.E.400 x) in the group of traditional Chinese medicine F, the uterus mucosa lamina propria (H.E.400 x) in the group of normal pregnancy, the uterus mucosa lamina propria (H.E.400 x) in the group of model H, the uterus mucosa lamina propria (H.E.400 x) in the group of traditional Chinese medicine I, and the uterus mucosa lamina propria (H.E.400 x) in the group of model J.
Detailed Description
Embodiment 1 a Chinese medicinal preparation for preventing and treating canine threatened abortion, which is prepared from the following Chinese medicinal raw materials in parts by weight (kg): 5 parts of fried scutellaria baicalensis, 5 parts of fried bighead atractylodes rhizome, 5 parts of astragalus mongholicus, 5 parts of eucommia ulmoides, 5 parts of codonopsis pilosula, 5 parts of angelica sinensis and 3 parts of liquorice.
The preparation method comprises the following steps:
⑴ are weighed according to the mixture ratio;
⑵ mixing parched radix Scutellariae, parched rhizoma Atractylodis Macrocephalae, radix astragali, cortex Eucommiae, radix Codonopsis, radix Angelicae sinensis, and radix Glycyrrhizae, decocting in water at a ratio of 1: 8 for 20min for 2 times, mixing decoctions, centrifuging at 1000r/min for 5min, and filtering to obtain Chinese medicinal liquid;
⑶ concentrating the Chinese medicinal liquid at 60 deg.C to obtain fluid extract with relative density of 1.13-1.15;
⑷ adding 0.05kg wetting agent and 0.1kg adhesive into the fluid extract according to 1kg, granulating, and spray drying at the inlet temperature of 180-220 deg.C and drying temperature of 60-80 deg.C for 5s to obtain Chinese medicinal granule with water content of 2-4%;
⑸ the traditional Chinese medicine particles are qualified by sampling inspection, 0.08kg of lubricant is added into 1kg of traditional Chinese medicine particles, and tablets with porosity of 2-10% are obtained after mixing and tabletting.
Embodiment 2 a Chinese medicinal preparation for preventing and treating canine threatened abortion, which is prepared from the following Chinese medicinal raw materials in parts by weight (kg): 6 parts of fried scutellaria baicalensis, 8 parts of fried bighead atractylodes rhizome, 8 parts of astragalus mongholicus, 6 parts of eucommia ulmoides, 8 parts of codonopsis pilosula, 6 parts of angelica sinensis and 4 parts of liquorice.
The preparation method comprises the following steps:
⑴ are weighed according to the mixture ratio;
⑵ mixing parched radix Scutellariae, parched rhizoma Atractylodis Macrocephalae, radix astragali, cortex Eucommiae, radix Codonopsis, radix Angelicae sinensis, and radix Glycyrrhizae, decocting in water at a ratio of 1: 10 for 20min for 2 times, mixing decoctions, centrifuging at 1500r/min for 8min, and filtering to obtain Chinese medicinal liquid;
⑶ concentrating the Chinese medicinal liquid at 60 deg.C to obtain fluid extract with relative density of 1.13-1.15;
⑷ adding 0.08kg wetting agent and 0.2kg adhesive into 1kg of the clear paste, granulating, and spray drying for 5s at the inlet temperature of a spray drying chamber of 180-220 ℃ and the drying temperature of 60-80 ℃ to obtain traditional Chinese medicine granules with the water content of 2-4%;
⑸ the traditional Chinese medicine particles are qualified by sampling inspection, 0.1kg of lubricant is added into 1kg of traditional Chinese medicine particles, and tablets with porosity of 2-10% are obtained after mixing and tabletting.
Embodiment 3 a Chinese medicinal preparation for preventing and treating canine threatened abortion, which is prepared from the following Chinese medicinal raw materials in parts by weight (kg): 8 parts of fried scutellaria baicalensis, 10 parts of fried bighead atractylodes rhizome, 10 parts of astragalus membranaceus, 10 parts of eucommia ulmoides, 10 parts of codonopsis pilosula, 8 parts of angelica sinensis and 5 parts of liquorice.
The preparation method comprises the following steps:
⑴ are weighed according to the mixture ratio;
⑵ mixing parched radix Scutellariae, parched rhizoma Atractylodis Macrocephalae, radix astragali, cortex Eucommiae, radix Codonopsis, radix Angelicae sinensis, and radix Glycyrrhizae, decocting in water at a ratio of 1: 10 for 20min for 2 times, mixing decoctions, centrifuging at 2000r/min for 10min, and filtering to obtain Chinese medicinal liquid;
⑶ concentrating the Chinese medicinal liquid at 60 deg.C to obtain fluid extract with relative density of 1.13-1.15;
⑷ adding 0.1kg wetting agent and 0.3kg adhesive into the fluid extract according to 1kg, granulating, and spray drying at the inlet temperature of 180-220 deg.C and drying temperature of 60-80 deg.C for 5s to obtain Chinese medicinal granule with water content of 2-4%;
⑸ the traditional Chinese medicine particles are qualified by sampling inspection, 0.12kg of lubricant is added into 1kg of traditional Chinese medicine particles, and tablets with porosity of 2-10% are obtained after mixing and tabletting.
In the above examples 1 to 3, the wetting agent is absolute ethyl alcohol. The binder is dextrin. The lubricant is magnesium stearate.
Claims (8)
1. A traditional Chinese medicine preparation for preventing and treating dog threatened abortion is characterized in that: the preparation is prepared from the following traditional Chinese medicine raw materials in parts by weight: 5-8 parts of fried scutellaria baicalensis, 5-10 parts of fried bighead atractylodes rhizome, 5-10 parts of astragalus membranaceus, 5-10 parts of eucommia ulmoides, 5-10 parts of codonopsis pilosula, 5-8 parts of angelica sinensis and 3-5 parts of liquorice.
2. The preparation method of the traditional Chinese medicine preparation for preventing and treating canine threatened abortion, which is disclosed by the claim 1, comprises the following steps:
⑴ are weighed according to the mixture ratio;
⑵ mixing radix Scutellariae preparata, rhizoma Atractylodis Macrocephalae preparata, radix astragali, cortex Eucommiae, radix Codonopsis, radix Angelicae sinensis, and radix Glycyrrhizae, decocting in water, centrifuging, and filtering to obtain Chinese medicinal liquid;
⑶ concentrating the Chinese medicinal liquid at 60 deg.C to obtain fluid extract with relative density of 1.13-1.15;
⑷ adding wetting agent and adhesive into the fluid extract, granulating, and spray drying to obtain Chinese medicinal granule with water content of 2-4%, wherein the mass ratio of the fluid extract to the wetting agent is 1: 0.05-0.1, and the mass ratio of the fluid extract to the adhesive is 1: 0.1-0.3;
⑸, adding a lubricant after the traditional Chinese medicine particles are qualified by sampling inspection, mixing and tabletting to obtain the tablet with the porosity of 2-10%, wherein the mass ratio of the traditional Chinese medicine particles to the lubricant is 1: 0.08-0.12.
3. The method for preparing a Chinese medicinal preparation for preventing and treating canine threatened abortion of claim 2, wherein the water decoction in the step ⑵ is performed at a ratio of 1: 8-12, and the number of times of decoction is 2, each time for 20 min.
4. The method for preparing a Chinese medicinal preparation for preventing and treating canine threatened abortion of claim 2, wherein the centrifugation in the step ⑵ is performed at a rate of 1000-2000 r/min for 5-10 min.
5. The method of claim 2, wherein the spray drying of step ⑷ is carried out at a spray drying chamber inlet temperature of 180-220 ℃, a drying temperature of 60-80 ℃, and a drying time of 5 s.
6. The method of claim 2, wherein the wetting agent used in step ⑷ is absolute ethanol.
7. The method of claim 2, wherein the binder of step ⑷ is dextrin.
8. The method for preparing a Chinese medicinal preparation for preventing and treating canine threatened abortion of claim 2, wherein the lubricant in step ⑸ is magnesium stearate.
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