Composition for relieving dysmenorrhea and anemia caused by cold coagulation and blood stasis as well as preparation method and application of composition

Abstract

The invention provides a composition for relieving cold coagulation and blood stasis dysmenorrhea and anemia and a preparation method and application thereof, and relates to the technical field of medicines, the composition comprises the following components in parts by weight: 1-2 parts of iron, 10.5-18.5 parts of magnesium and 0.4-1.0 part of zinc; iron is provided by hemin chloride, magnesium is provided by magnesium oxide, and zinc is provided by zinc oxide. After being absorbed by a proper amount of magnesium and zinc, blood vessel dilatation can be promoted, so that the blood flowing speed is increased, the blood pressure is reduced, iron absorption and utilization are further improved, iron is supplemented, and dysmenorrhea caused by unsmooth qi and blood circulation due to cold coagulation and blood stasis is relieved. The problems that a traditional iron supplementing agent is low in nutrient element intake, absorption and utilization rate and prone to causing diarrhea, vomiting and other gastrointestinal discomfort side effects are solved, and the technical problems that in the prior art, no medicine for treating dysmenorrhea and anemia caused by unsmooth qi and blood circulation due to cold coagulation and blood stasis exists, taking is inconvenient, and side effects exist are solved.

Description

Technical Field

[0001] The invention relates to the field of medical technology, and in particular to a composition for relieving dysmenorrhea and anemia caused by cold coagulation, blood stasis, and a preparation method and application thereof. Background Art

[0002] Cold blood stasis is a disease in traditional Chinese medicine, which refers to a state in which the blood becomes stagnant due to poor circulation of qi and blood due to cold factors, and accumulates in the meridians or tracheal tissues. This affects the overall balance of yin and yang, the circulation of qi and blood, and the function of internal organs. Especially in women, the invasion of cold evil causes qi and blood stagnation, poor circulation of qi and blood in the uterus, and uterine coldness causes abdominal pain during menstruation, and the clinical manifestation is qi and blood deficiency.

[0003] At present, drugs for treating dysmenorrhea are mainly for nourishing blood, activating blood circulation, activating meridians, warming meridians and dispelling cold, such as moxibustion and Chinese medicine conditioning. However, moxibustion requires burning to act on the body surface, which is inconvenient to use; Chinese medicine products have the problems of time-consuming decoction, bitter and difficult to drink, and restricted consumption temperature conditions. Iron supplements in Western medicine, such as ferrous sulfate, ferrous glucose, ferrous fumarate, etc., are all inorganic iron or plant iron. Their utilization rate in the body is low (absorption rate is generally 5%-8%), side effects are large (prone to nausea, bloating, digestive organ disorders, diarrhea, constipation and other symptoms), and they have a special metallic rust taste, which is difficult to consume for a long time.

[0004] In view of this, the present invention is proposed. Summary of the invention

[0005] One of the purposes of the present invention is to provide a composition for relieving dysmenorrhea and anemia caused by cold stagnation and blood stasis, so as to at least solve the technical problems in the prior art of lack of drugs for treating dysmenorrhea and anemia caused by poor circulation of qi and blood due to cold stagnation and blood stasis, which are inconvenient to take and have side effects.

[0006] The second object of the present invention is to provide a method for preparing a composition for relieving dysmenorrhea and anemia caused by cold stagnation and blood stasis.

[0007] The third object of the present invention is to provide the use of the above-mentioned composition or the combination prepared by the above-mentioned preparation method in the preparation of a drug for treating or alleviating dysmenorrhea and anemia caused by cold coagulation and blood stasis.

[0008] A fourth object of the present invention is to provide a medicine for treating or alleviating dysmenorrhea and anemia caused by cold coagulation and blood stasis.

[0009] In order to achieve the above-mentioned purpose of the present invention, the following technical solutions are particularly adopted:

[0010] In a first aspect, the present invention provides a composition for relieving dysmenorrhea and anemia caused by cold stagnation and blood stasis, comprising the following components in parts by weight: 1 to 2 parts of iron, 10.5 to 18.5 parts of magnesium, and 0.4 to 1.0 parts of zinc;

[0011] The iron is provided by hemin chloride, the magnesium is provided by magnesium oxide, and the zinc is provided by zinc oxide.

[0012] Further, the following components are included in parts by weight: 1.05 parts of iron, 16.75 parts of magnesium and 0.5 parts of zinc.

[0013] Furthermore, the zinc is provided by zinc oxide and zinc sulfate, and the mass ratio of zinc provided by zinc oxide to zinc provided by zinc sulfate is 1:0.8-1.

[0014] Furthermore, the Chinese medicine component comprises the following components in parts by weight: 15 to 20 parts of mulberry leaf extract, 24 to 32 parts of yam extract and 33 to 41 parts of wolfberry extract.

[0015] In a second aspect, the present invention provides a method for preparing the above-mentioned composition, comprising mixing hemin chloride particles, zinc and magnesium;

[0016] The particle size of the hemin chloride particles is ≤20 meshes.

[0017] Furthermore, the preparation method of the hemin chloride granules is wet granulation;

[0018] The wet granulation comprises mixing hemin chloride and water in a ratio of 4 to 6:1, granulating, and drying;

[0019] The drying temperature is 50-60°C;

[0020] The drying time is 5 to 7 hours.

[0021] Furthermore, the mixing of the hemin particles, zinc and magnesium comprises dissolving zinc in water and spraying the zinc-hemin particles, and after drying, dissolving magnesium in water and spraying the zinc-hemin particles, and drying to obtain magnesium-zinc-hemin particles;

[0022] The drying method is freeze drying.

[0023] Furthermore, when the composition also includes mulberry leaf extract, yam extract and wolfberry extract, the mixing of the hematin chloride particles, zinc and magnesium includes dissolving mulberry leaf extract and zinc in water and spraying them on the hematin chloride particles, and after freeze-drying, dissolving yam extract, wolfberry extract and magnesium in water and spraying them on the zinc-hematin chloride particles, and freeze-drying to obtain magnesium-zinc-hematin chloride particles.

[0024] In a third aspect, the present invention provides the use of the above-mentioned composition or the combination prepared by the above-mentioned preparation method in the preparation of a drug for treating or alleviating dysmenorrhea and anemia caused by cold coagulation and blood stasis.

[0025] In a fourth aspect, the present invention provides a drug for treating or alleviating dysmenorrhea and anemia caused by cold coagulation and blood stasis, comprising the above-mentioned composition or the combination prepared by the above-mentioned preparation method;

[0026] The dosage form of the drug is tablet, gel pill or oral solution.

[0027] The present invention provides a composition for relieving dysmenorrhea and anemia caused by cold stagnation and blood stasis, and ferric citrate is an iron supplement mainly used to treat iron deficiency anemia. Studies have found that ferric citrate is combined with magnesium and zinc in a ratio of 1 to 2 parts of iron, 10.5 to 18.5 parts of magnesium and 0.4 to 1.0 parts of zinc. After the appropriate amount of magnesium and zinc is absorbed, it can promote vasodilation, thereby increasing the blood flow rate, reducing blood pressure, and further improving iron absorption and utilization, so as to achieve iron supplementation and relieve dysmenorrhea caused by poor circulation of qi and blood due to cold stagnation and blood stasis. It avoids the problem of low absorption and utilization rate of large-scale intake of nutrients in traditional iron supplements, and is prone to side effects of gastrointestinal discomfort such as diarrhea and vomiting, and solves the technical problems of the lack of drugs for treating dysmenorrhea and anemia caused by poor circulation of qi and blood due to cold stagnation and blood stasis in the prior art, which are inconvenient to take and have side effects.

[0028] On the other hand, a preparation method of a composition for relieving dysmenorrhea and anemia caused by cold stagnation and blood stasis is provided. The hemin chloride is in the form of particles, which is convenient for mixing with zinc and magnesium. The particle size of the hemin chloride particles is limited to ≤20 meshes to avoid affecting the absorption and utilization of iron in the composition due to large particles. The composition prepared in this way can be used to prepare any dosage form of medicine for treating or relieving dysmenorrhea and anemia caused by cold stagnation and blood stasis. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0030] Figure 1 The hemoglobin concentration test results of different compositions provided in the experimental examples of the present invention acting on the animal model of cold coagulation, blood stasis, dysmenorrhea and anemia;

[0031] Figure 2 The red blood cell count results of different compositions provided in the experimental examples of the present invention acting on the animal model of cold coagulation, blood stasis, dysmenorrhea and anemia;

[0032] Figure 3 The hematocrit test results of different compositions provided in the experimental examples of the present invention acting on the animal model of cold coagulation, blood stasis, dysmenorrhea and anemia;

[0033] Figure 4 The results of hemoglobin concentration test on the animal model of dysmenorrhea due to cold stagnation, blood stasis and anemia 1 to 7 days after the last administration of different compositions provided in the experimental examples of the present invention. DETAILED DESCRIPTION

[0034] Unless otherwise defined herein, scientific and technical terms used in conjunction with the present invention shall have the meanings commonly understood by those of ordinary skill in the art. The meaning and scope of the terms should be clear, however, in the case of any potential ambiguity, the definitions provided herein take precedence over any dictionary or external definitions. In this application, unless otherwise stated, the use of "or" means "and / or". In addition, the use of the term "including" and other forms is non-limiting.

[0035] The methods and techniques of the present invention are generally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification unless otherwise indicated.

[0036] In one aspect, the present invention provides a composition for relieving dysmenorrhea and anemia caused by cold stagnation and blood stasis, comprising the following components in parts by weight: 1 to 2 parts of iron, 10.5 to 18.5 parts of magnesium and 0.4 to 1.0 parts of zinc;

[0037] The iron is provided by hemin chloride, the magnesium is provided by magnesium oxide, and the zinc is provided by zinc oxide.

[0038] Ferric Citrate is an iron supplement mainly used to treat iron deficiency anemia. It mainly contains iron and heme, and its structure is similar to the heme molecule in the human body, which is easily absorbed by the human body. Ferric Citrate is absorbed by the gastrointestinal mucosa in molecular form, which is mild and non-irritating. The absorption rate can reach 15%-25%, which can steadily increase hemoglobin and improve iron deficiency anemia. The inventors have found that the combination of ferric citrate with magnesium and zinc in the ratio of iron 1-2, magnesium 10.5-18.5 and zinc 0.4-1.0 can promote vasodilation after the absorption of appropriate amounts of magnesium and zinc, thereby increasing the blood flow rate, reducing blood pressure, and further improving iron absorption and utilization, so as to supplement iron and relieve dysmenorrhea caused by poor circulation of qi and blood due to cold stagnation and blood stasis. The invention avoids the problem that traditional iron supplements have a large intake of nutrients with low absorption rate and are prone to produce side effects of gastrointestinal discomfort such as diarrhea and vomiting. It solves the technical problem that the existing technology lacks drugs for treating dysmenorrhea and anemia caused by poor circulation of qi and blood due to cold stagnation and blood stasis, which are inconvenient to take and have side effects.

[0039] The weight proportion of the iron may be, but is not limited to, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9 or 2 parts, or any weight proportion between 1 and 2 parts;

[0040] The weight proportion of magnesium may be, but is not limited to, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18 or 18.5, or any weight proportion between 10.5 and 18.5.

[0041] The weight proportion of zinc may be, but is not limited to, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95 or 1.0, and may be any weight proportion between 0.4 and 1.0.

[0042] In some specific embodiments, the following components are included in weight: 1.05 parts of iron, 16.75 parts of magnesium and 0.5 parts of zinc, which further improves the effect of relieving cold-coagulated blood stasis, dysmenorrhea and anemia.

[0043] In some specific embodiments, the zinc is provided by zinc oxide and zinc sulfate, and the mass ratio of zinc provided by zinc oxide to zinc provided by zinc sulfate is 1:0.8-1.

[0044] By using zinc oxide and zinc sulfate in a ratio of 1:0.8-1, zinc is absorbed by the human body in two parts. One part of zinc oxide is absorbed in advance in the stomach, promoting vascular dilation, improving the body's poor blood flow, and promoting further absorption of iron and magnesium. The other part of zinc sulfate is absorbed in the intestines and cooperates with magnesium to further promote vascular expansion and iron absorption. This combination improves the absorption and utilization rate of zinc and the promoting effect of zinc and other components.

[0045] The ratio of zinc oxide to zinc sulfate may be, but is not limited to, 1:0.8, 1:0.82, 1:0.84, 1:0.86, 1:0.88, 1:0.9, 1:0.92, 1:0.94, 1:0.96, 1:0.98 or 1:1, or any ratio between 1:0.8 and 1.

[0046] In some specific embodiments, the Chinese medicine component is further comprised of the following components in parts by weight: 15-20 parts of mulberry leaf extract, 24-32 parts of yam extract and 33-41 parts of wolfberry extract.

[0047] Mulberry leaves: rich in selenium, often used to clear away heat, detoxify and lower blood sugar.

[0048] Wolfberry: In addition to being rich in trace elements such as iron and zinc, it also contains a certain amount of selenium, which is often used to nourish the liver and kidneys, improve eyesight and nourish the body.

[0049] Yam: Contains a certain amount of selenium, which has the effects of nourishing the spleen and lungs, nourishing blood and calming the mind.

[0050] By adding wolfberry extract to supplement the trace elements of iron and zinc from biological sources, and adding mulberry leaf extract and yam extract to supplement the trace element selenium, the inner wall of blood vessels is protected from damage, which helps to maintain the health and elasticity of blood vessels, indirectly promotes blood circulation, and improves the effect of relieving cold blood stasis, dysmenorrhea and anemia.

[0051] According to another aspect of the present invention, there is also provided a method for preparing the above-mentioned composition, characterized in that it comprises mixing hemin chloride particles, zinc and magnesium;

[0052] The particle size of the hemin chloride particles is ≤20 meshes.

[0053] The hemin chloride is convenient to mix with zinc and magnesium in the form of granules, and the particle size of the hemin chloride granules is limited to ≤20 meshes to avoid affecting the absorption and utilization of iron in the composition due to large particles. The composition prepared in this way can be used to prepare any dosage form of medicine for treating or relieving dysmenorrhea and anemia caused by cold coagulation and blood stasis.

[0054] In some specific embodiments, the preparation method of the hemin granules is wet granulation.

[0055] Specifically, a high-speed mixing wet granulation process can be used, wherein a batch amount of hemin chloride is weighed and added to a wet granulator, and high-speed stirring and high-speed shearing are started while adding purified water, and granulation is performed after adding purified water. Hemin chloride and water are stirred and mixed in a ratio of 4 to 6:1, and then granulated and dried; the drying temperature is 50 to 60° C.; and the drying time is 5 to 7 hours.

[0056] In some specific embodiments, the mixing of the hemin particles, zinc and magnesium comprises dissolving zinc in water and spraying the zinc-hemin particles, and after drying, dissolving magnesium in water and spraying the zinc-hemin particles, and drying to obtain magnesium-zinc-hemin particles;

[0057] The drying method is freeze drying.

[0058] Zinc and magnesium are compounded with hemin chloride particles in sequence to make granules, so that the hemin chloride particles, zinc and magnesium are evenly mixed. Since it is a composite particle, the digestion and absorption rate of each component is kept stable. Zinc is on the outermost side, which helps zinc oxide to be released and absorbed in the stomach, thereby improving the effect of the composition.

[0059] In some specific embodiments, when the composition further includes mulberry leaf extract, yam extract and wolfberry extract, the mixing of the hematin particles, zinc and magnesium includes dissolving mulberry leaf extract and zinc in water and spraying them on the hematin particles, and after freeze-drying, dissolving yam extract, wolfberry extract and magnesium in water and spraying them on the zinc-hematin particles, and freeze-drying to obtain magnesium-zinc-hematin particles.

[0060] By mixing mulberry leaf extract with zinc, yam extract and wolfberry extract with magnesium and then spraying them on the hematin particles, the medicinal effects of mulberry leaf extract, yam extract and wolfberry extract can be fully exerted, and the effect of treating or alleviating dysmenorrhea and anemia caused by cold stagnation and blood stasis can be improved.

[0061] According to another aspect of the present invention, there is also provided the use of the above-mentioned composition or the combination prepared by the above-mentioned preparation method in the preparation of a drug for treating or alleviating dysmenorrhea and anemia caused by cold coagulation and blood stasis.

[0062] According to another aspect of the present invention, there is also provided a medicine for treating or alleviating dysmenorrhea and anemia caused by cold coagulation and blood stasis, comprising the above composition or the combination prepared by the above preparation method.

[0063] Wherein, the dosage form of the drug is tablets, gel pills or oral liquid.

[0064] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0065] Mulberry leaf extract was purchased from Xi’an Dongchi Biotechnology Co., Ltd., catalog number DC20113011;

[0066] Chinese yam extract was purchased from Xi’an Dongchi Biotechnology Co., Ltd., catalog number DC20112403;

[0067] Lycium barbarum extract was purchased from Xi'an Dongchi Biotechnology Co., Ltd., product number DC20120115.

[0068] Example 1

[0069] A composition for relieving dysmenorrhea and anemia caused by cold stagnation, blood stasis and the like, comprises the following components in parts by weight: 1.05 parts of iron, 16.75 parts of magnesium and 0.5 parts of zinc, wherein the raw material of iron is hemin chloride, the raw material of magnesium is magnesium oxide and the raw material of zinc is zinc oxide.

[0070] Example 2

[0071] A composition for relieving dysmenorrhea and anemia caused by cold stagnation, blood stasis and the like, comprises the following components in parts by weight: 1 part of iron, 18.5 parts of magnesium and 1.0 part of zinc, wherein the raw material of iron is hemin chloride, the raw material of magnesium is magnesium oxide and the raw material of zinc is zinc oxide.

[0072] Example 3

[0073] A composition for relieving dysmenorrhea and anemia caused by cold stagnation, blood stasis and the like, comprises the following components in parts by weight: 2 parts of iron, 10.5 parts of magnesium and 0.4 parts of zinc, wherein the raw material of iron is hemin chloride, the raw material of magnesium is magnesium oxide and the raw material of zinc is zinc oxide.

[0074] Example 4

[0075] A composition for relieving dysmenorrhea and anemia caused by cold stagnation, blood stasis, and the composition comprises the following components in parts by weight: 1.05 parts of iron, 16.75 parts of magnesium, and 0.5 parts of zinc, wherein the iron raw material is hemin chloride, the magnesium raw material is magnesium oxide, and the zinc raw materials are zinc oxide and zinc sulfate, and the ratio of zinc oxide to zinc sulfate is 1:1.

[0076] Example 5

[0077] The difference from Example 4 is that the zinc raw materials are zinc oxide and zinc sulfate, and the ratio of zinc oxide to zinc sulfate is 1:0.8.

[0078] Example 6

[0079] A composition for relieving dysmenorrhea and anemia caused by cold stagnation, blood stasis, and the like, comprising the following components in parts by weight: a Chinese medicinal component consisting of 1.05 parts of iron, 16.75 parts of magnesium, 0.5 parts of zinc, 17 parts of mulberry leaf extract, 29 parts of yam extract, and 37 parts of wolfberry extract, wherein the iron raw material is hemin chloride, the magnesium raw material is magnesium oxide, and the zinc raw material is zinc oxide.

[0080] Example 7

[0081] A composition for relieving dysmenorrhea and anemia caused by cold stagnation, blood stasis, and the like, comprising the following components in parts by weight: a Chinese medicinal component consisting of 1.05 parts of iron, 16.75 parts of magnesium, 0.5 parts of zinc, 15 parts of mulberry leaf extract, 32 parts of yam extract, and 33 parts of wolfberry extract, wherein the iron raw material is hemin chloride, the magnesium raw material is magnesium oxide, and the zinc raw material is zinc oxide.

[0082] Example 8

[0083] A composition for relieving dysmenorrhea and anemia caused by cold stagnation, blood stasis, and the like, comprising the following components in parts by weight: a Chinese medicinal component consisting of 1.05 parts of iron, 16.75 parts of magnesium, 0.5 parts of zinc, 20 parts of mulberry leaf extract, 24 parts of yam extract, and 41 parts of wolfberry extract, wherein the iron raw material is hemin chloride, the magnesium raw material is magnesium oxide, and the zinc raw material is zinc oxide.

[0084] Comparative Example 1

[0085] The difference from Example 1 is that the iron raw material is ferrous sulfate.

[0086] Comparative Example 2

[0087] The same as in Example 1, the magnesium raw material is magnesium citrate.

[0088] Comparative Example 3

[0089] The same as in Example 1, the zinc raw material is zinc gluconate.

[0090] Comparative Example 4

[0091] The difference from Example 1 is that the amount of magnesium is 10 parts by weight.

[0092] Comparative Example 5

[0093] The difference from Example 1 is that the amount of magnesium is 19 parts by weight.

[0094] Comparative Example 6

[0095] The difference from Example 1 is that the amount of zinc is 0.3 parts by weight.

[0096] Comparative Example 7

[0097] The difference from Example 1 is that the amount of zinc is 1.1 parts by weight.

[0098] Examples 9 to 13

[0099] A method for preparing a composition for relieving dysmenorrhea and anemia caused by cold stagnation, blood stasis, and the compositions of Examples 1 to 5 are prepared respectively according to the following methods:

[0100] 1) Preparation of hemin granules

[0101] Prepare the raw materials and auxiliary materials in advance and clean the equipment.

[0102] The high-speed mixing wet granulation process was adopted. The batch amount of hemin chloride was weighed and added to the wet granulator. The purified water was added and high-speed stirring and high-speed shearing were started. After adding purified water in a ratio of 5:1, the hemin chloride and water were granulated for 40±10s, and the granulation effect was observed to make granules under 20 mesh. The prepared granules were placed in a 55°C oven and dried for 6 hours, and the material was turned over every 2 hours. The vibrating screen was sieved with a 20-mesh national standard screen, and the dry granules were sieved through a 20-mesh screen to obtain the sieve.

[0103] 2) The zinc raw material, the magnesium raw material and the hemin chloride particles are uniformly mixed to obtain a composition for later use.

[0104] Comparative Examples 8 to 14

[0105] Different from Example 9, the compositions of Comparative Examples 1 to 7 were prepared.

[0106] Embodiment 14

[0107] The difference from Example 9 is that in step 2), magnesium is dissolved in water and sprayed on the hemin particles, and after freeze-drying, zinc is dissolved in water and sprayed on the hemin particles, and freeze-dried to obtain a composition for later use.

[0108] Embodiments 15 to 17

[0109] A method for preparing a composition for relieving dysmenorrhea and anemia caused by cold coagulation, blood stasis, and the compositions of Examples 7 to 9 are prepared respectively according to the following methods:

[0110] 1) Preparation of hemin granules

[0111] Prepare the raw materials and auxiliary materials in advance and clean the equipment.

[0112] The high-speed mixing wet granulation process was adopted. The batch amount of hemin chloride was weighed and added to the wet granulator. The purified water was added and high-speed stirring and high-speed shearing were started. After adding purified water in a ratio of 5:1, the hemin chloride and water were granulated for 40±10s, and the granulation effect was observed to make granules under 20 mesh. The prepared granules were placed in a 55°C oven and dried for 6 hours, and the material was turned over every 2 hours. The vibrating screen was sieved with a 20-mesh national standard screen, and the dry granules were sieved through a 20-mesh screen to obtain the sieve.

[0113] 2) dissolving mulberry leaf extract and zinc in water and spraying them on the hemin particles, freeze-drying them, dissolving yam extract, wolfberry extract and magnesium in water and spraying them on the hemin particles, freeze-drying them to obtain a composition.

[0114] Embodiment 18

[0115] The difference from Example 15 is that in step 2), the mulberry leaf extract, the yam extract, the wolfberry extract, the raw material magnesium, the raw material zinc and the hemin chloride particles are uniformly mixed to obtain a composition.

[0116] Effect of experimental example composition on dysmenorrhea caused by cold stagnation and blood stasis

[0117] 1. Experimental animals: SPF mature female SD rats, 7 weeks old, unmated, and adaptively raised for 7 days. During the animal breeding process, the animals were given 12-h circadian rhythm lighting, controlled temperature at 23±2℃, humidity at 40%-60%, and free access to water and food.

[0118] For experimental grouping, the experimental rats were randomly divided into 17 experimental groups, and a control group and a normal group were set up, with 8 rats in each group.

[0119] Construction of a rat model of dysmenorrhea caused by cold stagnation, blood stasis and anemia: except for the normal group, rats in other groups were gavaged with estradiol valerate 3 mg / kg daily. One hour after gavage, rats in other groups, except for the normal group, were immersed in 0-1℃ ice water once a day for 10 min each time for 14 consecutive days. At the same time, except for the normal group which was fed with normal feed, rats in other groups were fed with low-iron feed with an iron content of 7.96μg / g. After an ice bath for 1 hour, the rats were bled from the tail every other day, with a bloodletting volume of 1.5-2ml / rat, for 5 consecutive times.

[0120] The symptoms of rats were used as indicators of successful modeling of cold stagnation and blood stasis syndrome: rats shivered, curled up, liked to gather together, were drowsy, had dull eyes, slow reaction, weak breathing, decreased body temperature, slowed heartbeat, arched back and erect hair, dull hair color, dark purple nails, dark red ears, black lips, dark purple tongue, thickened and enlarged sublingual veins, dark lower abdomen and perianal area, clear urine, and soft and unformed stools; rats' twisting reaction was used as an indicator of successful PD modeling: the abdomen contracted and concave, the trunk and hind limbs extended, and the buttocks and one side of the limbs rotated inward. The hemoglobin content dropped to 86.94g / L, which was an indicator of successful modeling of anemia. The modeling success rate according to the above indicators was 100%.

[0121] 2. Medication intervention

[0122] The drug dosage was 0.12 g / kg per day. The compositions prepared in Examples 9 to 18 and Comparative Examples 8 to 14 were prepared into solutions with physiological saline. The administration by gavage began on the second day of modeling. The experimental group was gavaged with the compositions prepared in Examples 9 to 18 and Comparative Examples 8 to 14, and the normal group and the model group were given the same amount of distilled water. The administration was continued for 10 days.

[0123] 3. Index determination

[0124] 1) Determination of writhing reaction: 1 hour after the last administration, oxytocin 14 IU / kg was injected intraperitoneally into the other groups except the normal group. The recognized writhing reaction (i.e., abdominal contraction and concavity, trunk and hind limb extension, hip and one side limb internal rotation) was used as an indicator to observe the writhing reaction time and the number of writhing times within 30 minutes.

[0125] 2) Blood index detection: After the last administration and the writhing reaction test, blood was collected from the tail vein to detect the hemoglobin (HGB) concentration, red blood cell (RBC) count and hematocrit (HCT). For Example 9 and Examples 15 to 17, blood was collected from the tail vein to detect the hemoglobin (HGB) concentration, red blood cell (RBC) count and hematocrit (HCT) change values ​​1d, 3d, 5d and 7d after the last administration.

[0126] 4. Results

[0127] 1) The statistical results of the twisting reaction are shown in Table 1.

[0128] Table 1 The writhing reaction results of different compositions on the animal model of cold stagnation, blood stasis, dysmenorrhea and anemia

[0129] Group Twist reaction time / min Number of body twists within 30 minutes Normal group 19.67 2.50 Control group 5.50 19.67 Example 9 17.83 5.00 Example 10 17.17 4.00 Embodiment 11 17.00 6.00 Example 12 18.17 3.17 Embodiment 13 18.83 3.83 Embodiment 14 18.50 5.17 Embodiment 15 17.50 3.00 Example 16 17.67 3.17 Embodiment 17 18.33 2.50 Embodiment 18 17.33 3.50 Comparative Example 8 11.50 11.00 Comparative Example 9 12.17 9.00 Comparative Example 10 13.83 9.83 Comparative Example 11 14.83 8.17 Comparative Example 12 14.33 9.17 Comparative Example 13 14.67 7.83 Comparative Example 14 14.00 10.50

[0130] Compared with the control group, the latent time of Examples 9 to 10 was increased and the number of twisting times was reduced, indicating that the composition prepared from the corresponding raw materials of 1 to 2 parts by weight of iron, 10.5 to 18.5 parts by weight of magnesium and 0.4 to 1.0 parts by weight of zinc has the effect of relieving dysmenorrhea caused by cold stagnation and blood stasis.

[0131] Compared with Example 9, the incubation times of Comparative Examples 8 to 10 are all shorter than that of Example 9, and the number of twisting times is increased, indicating that not all combinations of iron, magnesium and zinc from any source can achieve the effect of relieving dysmenorrhea caused by cold stagnation and blood stasis; the increase in the number of twisting times of Comparative Examples 11 to 14 indicates that excessive reduction or increase in the amount of magnesium or zinc used leads to a weakened effect of relieving dysmenorrhea caused by cold stagnation and blood stasis.

[0132] Compared with Example 9, the number of twisting times in Example 12 and Example 13 is further reduced, indicating that the combination of zinc oxide and zinc sulfate as zinc raw materials can improve the effect of relieving cold, blood stasis and dysmenorrhea.

[0133] Compared with Example 9, the latent time of Example 14 increased, indicating that the preparation method of Example 14 can improve the effect of the composition in relieving dysmenorrhea caused by cold stagnation and blood stasis. The latent time of Examples 15 to 17 did not change significantly, but the number of twistings was significantly lower than that of Examples 9 to 13, indicating that the addition of mulberry leaf extract, yam extract and wolfberry extract has a promoting effect on relieving dysmenorrhea caused by cold stagnation and blood stasis.

[0134] Compared with Example 15, the latent time of Example 18 is shorter and the number of twisting times is increased, indicating that the preparation method of directly mixing mulberry leaf extract, yam extract and wolfberry extract with magnesium, iron and zinc raw materials is not conducive to the effect of the composition in relieving dysmenorrhea caused by cold stagnation and blood stasis.

[0135] 2) Blood test results such as Figure 1 to Figure 4 shown.

[0136] Depend on Figure 1 to Figure 3 It can be seen that the blood indexes of Examples 9 to 18 are all higher than those of the comparative examples, among which the HGB content of Examples 12 to 14 is higher than that of Example 9, indicating that the combination of zinc oxide and zinc sulfate as the raw material zinc and the preparation method of spraying the magnesium raw material and the zinc raw material on the hematin chloride particles can improve the effect of the composition in improving anemia. The HGB and RBC of Examples 15 to 17 are not significantly different from those of Example 9. Figure 4It can be seen that compared with Example 9, the blood indicators of Examples 15 to 17 exceeded those of Example 9 1 day after the last administration, indicating that the composition with added mulberry leaf extract, yam extract and wolfberry extract can accelerate the recovery of anemia.

[0137] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A composition for relieving dysmenorrhea and anemia caused by cold stagnation and blood stasis, characterized in that: The invention comprises the following components in parts by weight: 1 to 2 parts of iron, 10.5 to 18.5 parts of magnesium and 0.4 to 1.0 parts of zinc; The iron is provided by hemin chloride, the magnesium is provided by magnesium oxide, and the zinc is provided by zinc oxide.

2. The composition according to claim 1, characterized in that The composition comprises the following components in parts by weight: 1.05 parts of iron, 16.75 parts of magnesium and 0.5 parts of zinc.

3. The composition according to claim 1, characterized in that The zinc is provided by zinc oxide and zinc sulfate, and the mass ratio of zinc provided by zinc oxide to zinc provided by zinc sulfate is 1:0.8-1.

4. The composition according to any one of claims 1 to 3, characterized in that The invention also comprises the following components in parts by weight: a traditional Chinese medicine component consisting of 15 to 20 parts of mulberry leaf extract, 24 to 32 parts of yam extract and 33 to 41 parts of wolfberry extract.

5. The method for preparing the composition according to any one of claims 1 to 4, characterized in that: The method comprises mixing hemin granules, zinc and magnesium to obtain a composition; The particle size of the hemin chloride particles is ≤20 meshes.

6. The preparation method according to claim 5, characterized in that: The preparation method of the hemin granules is wet granulation; The wet granulation comprises mixing hemin chloride and water in a ratio of 4 to 6:1, granulating, and drying; The drying temperature is 50-60°C; The drying time is 5 to 7 hours.

7. The preparation method according to claim 5, characterized in that: The method of mixing hemin particles, zinc and magnesium comprises dissolving zinc in water and spraying the zinc on the hemin particles, drying the zinc, dissolving magnesium in water and spraying the magnesium on the hemin particles, and drying the magnesium to obtain a composition. or, Dissolving magnesium in water and spraying it onto the hemin particles, and after drying, dissolving zinc in water and spraying it onto the hemin particles, and drying to obtain a composition; The drying method is freeze drying.

8. The preparation method according to claim 7, characterized in that: When the composition further comprises mulberry leaf extract, yam extract and wolfberry extract, the mixing of the hemin granules, zinc and magnesium comprises dissolving the mulberry leaf extract and zinc in water and spraying the dissolved mulberry leaf extract and zinc on the hemin granules, freeze-drying the dissolved yam extract, wolfberry extract and magnesium in water and spraying the dissolved yam extract and wolfberry extract on the hemin granules, freeze-drying the dissolved yam extract and magnesium to obtain the composition; or The yam extract, wolfberry extract and magnesium are dissolved in water and sprayed on the hemin granules. After freeze-drying, the mulberry leaf extract and zinc are dissolved in water and sprayed on the hemin granules. The composition is freeze-dried to obtain the composition.

9. Use of the composition according to any one of claims 1 to 4 or the combination prepared by the preparation method according to any one of claims 5 to 8 in the preparation of a medicament for treating or alleviating dysmenorrhea and anemia caused by cold coagulation and blood stasis.

10. A drug for treating or alleviating dysmenorrhea and anemia caused by cold stagnation and blood stasis, characterized in that: A composition comprising the composition of any one of claims 1 to 4 or a combination prepared by the preparation method of any one of claims 5 to 8; The dosage form of the drug is tablet, gel pill or oral solution.

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