CN105770078B

CN105770078B - Pharmaceutical composition, preparation and application thereof

Info

Publication number: CN105770078B
Application number: CN201610144586.8A
Authority: CN
Inventors: 魏利夫; 李春艳; 耿华; 宋冬梅
Original assignee: Liaoning Taiyang Pharmaceutical Technology Development Co ltd
Current assignee: Liaoning Taiyang Pharmaceutical Technology Development Co ltd
Priority date: 2016-03-13
Filing date: 2016-03-13
Publication date: 2020-11-06
Anticipated expiration: 2036-03-13
Also published as: CN105770078A

Abstract

The invention belongs to the technical field of traditional Chinese medicines or health-care foods, and particularly relates to a pharmaceutical composition, a preparation and an application thereof, wherein the pharmaceutical composition is prepared into a pharmaceutical preparation, and the pharmaceutical preparation is prepared from the following raw materials: donkey-hide gelatin, ginseng, rose, sea buckthorn, roxburgh rose, mulberry and raspberry. Pharmacodynamic studies show that the composition has good effects of improving immunity, enriching blood, resisting fatigue and the like.

Description

Pharmaceutical composition, preparation and application thereof

Technical Field

The invention belongs to the technical field of traditional Chinese medicines or health-care food, and particularly relates to a pharmaceutical composition containing traditional Chinese medicines such as donkey-hide gelatin and ginseng, and a preparation and application thereof.

Background

Donkey-hide gelatin (Colla Corii Asini) is a gelatin block prepared by decocting and concentrating dried or fresh skin of Equus asinusL, an animal of Equidae, is a traditional and rare Chinese medicine in China, is called 'three treasures of traditional Chinese medicine' together with ginseng and pilose antler, and is called 'Sheng Xue Buxue Sheng' medicine. The Shennong Bencao Jing records that donkey-hide gelatin is prepared by decocting donkey hide. Donkey-hide gelatin is sweet in flavor and neutral in nature, and enters lung, liver and kidney meridians. Colla Corii Asini has effects of replenishing blood, nourishing yin, moistening dryness, and stopping bleeding. Li Shizhen is also recorded in Ben Cao gang mu in great detail: "treat hematemesis, epistaxis, bloody stranguria, hematuria, intestinal wind and dysentery, female blood pain and blood depletion, irregular menstruation, leukorrhagia, antenatal and postpartum diseases, all wind diseases of male and female, bone joint pain, edema of water and gas, consumptive disease and cough, dyspnea, lung withering and saliva and pus blood, carbuncle and toxic swelling, blood nourishing, wind dispelling and dryness moistening, phlegm reducing, lung heat clearing and urination promoting, intestine regulating, and holy medicine are also used. "

The current theories about the pharmacological action mechanism of donkey-hide gelatin mainly include: the theory of amino acid and trace element, and the theory of poly-anion group structure. The theory of amino acids and trace elements considers that the blood-enriching function of donkey-hide gelatin is caused by the fact that donkey-hide gelatin contains essential amino acids and trace elements, and the research result is approved by most scholars. The glycine in the donkey-hide gelatin promotes the synthesis of hemoglobin by regulating serum iron; arginine can increase the secretion of growth hormone and testosterone of organism and promote the synthesis of hemoglobin; threonine, histidine and lysine all have hematogenesis effect. The donkey-hide gelatin is rich in iron element and a large amount of animal protein, is an iron supplement which is easy to absorb, can increase the intake of the iron element in a body after being taken for a long time, recovers the physiological function of the iron element in the body, and effectively controls iron-deficiency anemia. Copper is an important component of several tens of enzymes and a constituent element of erythrocytes, promotes the utilization of iron and the hematopoietic process, and participates in the immune mechanism and the synthesis of elastin. The colla Corii Asini can supplement essential copper element, accelerate absorption and utilization of iron, and make absorbed iron and microelements such as manganese cooperate to produce hematogenesis effect. The theory of poly-anion-based structure considers that in the preparation process of donkey-hide gelatin, hydrophobic collagen completes the structural transformation of 'hydrophilic colloid' under the action of factors such as temperature, moisture, time and the like to form a unique poly-anion-based structure. The anion group can adjust the affinity of oxygen and hemoglobin; the negative ion group in factors such as Epidermal Growth Factor (EGF) may be critical for the angiogenic effect; during the immune, infection and inflammation processes, the formation of negative ion groups can cause resistance to the bacteria passing through cells, and a barrier is formed; in the hemostatic and anticoagulant processes, the activity of glycosaminoglycan (GAG) having negative ion groups is proportional to the length of its polymer and the number of negative ions of the bound polysaccharide, and thus the blood coagulation status can be adjusted. The two theories satisfactorily explain the action mechanisms of donkey-hide gelatin for enriching blood, supplementing calcium, enhancing immunity and the like. Regarding the hemostatic action mechanism of donkey-hide gelatin, the inventor thinks that it is related to the decrease of the permeability of the blood vessel wall and the increase of the number of platelets; it is also associated with collagen adhesion to the vessel wall to promote platelet aggregation; in recent years, the dermatan sulfate and proteoglycan thereof contained in the donkey-hide gelatin have a poly-anion group structure and various biological activities, are closely related to various effects of hemostasis, anti-thrombosis, anti-inflammation, anti-tumor, anti-infection, injury repair and the like, and are worthy of further intensive research. At present, the curative effect of donkey-hide gelatin is that what ingredients act on what parts of human body and are absorbed, distributed and excreted in what way, and the research on the action mechanism of donkey-hide gelatin is still in the research stage. It is believed that the clinical medical and health-care functions of donkey-hide gelatin, such as blood enriching, hemostasis, miscarriage prevention, aging resistance, shock resistance, tumor resistance, immunity enhancement, calcium absorption and storage, and the like, are cracked by means of modern high-tech means such as genetic engineering, molecular biology, cell biology and the like, and relevant effective components and action mechanisms of the donkey-hide gelatin are determined.

In summary, research and development of traditional Chinese medicines or health foods containing donkey-hide gelatin are necessary, so as to further promote the development of the modernization of donkey-hide gelatin traditional Chinese medicines.

Disclosure of Invention

Based on the reasons, the applicant invents a novel pharmaceutical composition through years of clinical research, based on the theory of traditional Chinese medicine and combined with modern medical research, and the composition comprises the following raw materials: donkey-hide gelatin, ginseng, rose, sea buckthorn, roxburgh rose, mulberry and raspberry. Pharmacodynamic studies show that the composition has good effects of improving immunity, enriching blood, resisting oxidation and the like.

The composition of the invention contains donkey-hide gelatin, which is sweet and mild. It enters lung, liver and kidney meridians. Tonify blood, nourish yin, moisten dryness. Is rich in collagen and amino acids. Is beneficial to hematopoiesis, blood vessel dilatation, beauty maintenance and face care and immunity enhancement. Ginseng is sweet, slightly bitter and warm. It enters spleen, lung, heart and kidney meridians. Tonify primordial qi, recover pulse to stop collapse, tonify spleen and lung, promote the production of body fluid and nourish blood, induce tranquilization and promote intelligence. Is rich in saponin, amino acids, and polysaccharide. Has obvious effects of enhancing immunity and resisting oxidation. Rose flower, sweet, slightly bitter and slightly cold. It enters lung and stomach meridians. Move qi and relieve depression, harmonize blood, alleviate pain. Is rich in volatile oil, eugenol, total flavonoids, and VC. Seabuckthorn fruit, sweet, slightly bitter and slightly cold. It enters lung and stomach meridians. Invigorate spleen to promote digestion, relieve cough and eliminate phlegm, activate blood and dissipate blood stasis. Is rich in flavonoids, triterpene steroids, vitamin A, B, C, E, and folic acid. Has obvious effects of enhancing immunity, resisting tumor, improving cardiac function and resisting aging. The roxburgh rose is a natural plant used as both medicine and food, is rich in VC, is a fruit used as both medicine and food for building body, preventing and treating diseases, and has the functions of regulating the immunity of the organism, delaying senility, resisting atherosclerosis, resisting tumors and the like. Mulberry fruit, sweet, sour and cold. It enters heart, liver and kidney meridians. Nourish yin and enrich blood, promote fluid production and moisten dryness. Is rich in rutin, VB1, VB2, VC and anthocyanin. Has good effects in enhancing immunity, promoting cell maturation, promoting hematopoiesis, lowering blood pressure, caring skin, and resisting oxidation. Rubi fructus is sweet, slightly bitter and slightly cold. It enters lung and stomach meridians. To tonify kidney, secure essence, reduce urination, nourish liver and improve vision. Is rich in polysaccharide, VC and organic acid. Has remarkable antibacterial and anti-aging effects.

The donkey-hide gelatin and the ginseng in the formula are combined to be monarch drug, so that the purposes of nourishing yin and enriching blood, moistening dryness and promoting the production of body fluid and supplementing vitality are achieved, and the purposes of enhancing immunity, resisting oxidation, delaying senility, maintaining beauty and keeping young are achieved. The rose and the sea buckthorn have good effects of resisting oxidation and delaying senescence, and are used together as ministerial drugs for assisting donkey-hide gelatin and ginseng to enhance the effect. Fructus Rosae Normalis, Mori fructus, and Rubi fructus can be added to achieve immunity enhancing and antioxidant effects. The ingredients are combined to play the effects of enhancing immunity, resisting oxidation, delaying senility and maintaining beauty and keeping young.

The invention is realized by the following technical scheme.

A pharmaceutical composition is prepared into a pharmaceutical preparation, wherein the pharmaceutical preparation is prepared from the following raw materials: donkey-hide gelatin, ginseng, rose, sea buckthorn, roxburgh rose, mulberry and raspberry.

The preferable pharmaceutical composition comprises 4-6 parts by weight of donkey-hide gelatin, 4-6 parts by weight of ginseng, 4-6 parts by weight of rose, 8-12 parts by weight of sea buckthorn, 8-12 parts by weight of roxburgh rose, 8-12 parts by weight of mulberry and 8-12 parts by weight of raspberry.

The preferable pharmaceutical composition comprises 5 parts by weight of donkey-hide gelatin, 5 parts by weight of ginseng, 5 parts by weight of rose, 10 parts by weight of sea buckthorn, 10 parts by weight of rosa roxburghii, 10 parts by weight of mulberry and 10 parts by weight of raspberry.

The pharmaceutical composition is characterized by being applied to preparation of a medicine or food for improving immunity.

The pharmaceutical composition is characterized by application of the pharmaceutical composition in preparation of blood enriching medicines or foods.

The pharmaceutical composition is characterized by being applied to the preparation of anti-fatigue drugs or foods.

The pharmaceutical composition comprises an oral preparation.

The pharmaceutical composition, wherein the pharmaceutical preparation comprises a wine.

The preparation method of the wine comprises the following steps:

soaking Ginseng radix, flos Rosae Rugosae, fructus Hippophae, fructus Rosae Normalis, Mori fructus, and Rubi fructus in dry red wine for 6-18 hr, and filtering; melting colla Corii Asini with purified water to obtain colla Corii Asini solution; and finally, adding the donkey-hide gelatin solution, the blueberry concentrated juice, the xylitol and the aspartame into the wine, uniformly stirring, filtering, filling, externally packaging, inspecting and warehousing.

Detailed Description

Pharmacodynamic experiment

Test example 1 Immunity-improving test

Test animals: BALB/C male mice, weight 18-20 g.

Test drugs:

test 1 group: 4g of donkey-hide gelatin, 4g of ginseng, 4g of rose, 8g of sea buckthorn, 8g of rosa roxburghii tratt, 8g of mulberry and 8g of raspberry.

Test 2 groups: 6g of donkey-hide gelatin, 6g of ginseng, 6g of rose, 12g of sea buckthorn, 12g of rosa roxburghii tratt, 12g of mulberry and 12g of raspberry.

Run 3 groups: 5g of donkey-hide gelatin, 5g of ginseng, 5g of rose, 10g of sea buckthorn, 10g of rosa roxburghii tratt, 10g of mulberry and 10g of raspberry.

Run 4 groups: 4.5g of donkey-hide gelatin, 5g of ginseng, 4.5g of rose, 8.5g of sea buckthorn, 10g of roxburgh rose, 10g of mulberry and 9g of raspberry.

Run 5 groups: 5.5g of donkey-hide gelatin, 6g of ginseng, 5g of rose, 11g of sea buckthorn, 10.5g of roxburgh rose, 10.5g of mulberry and 12g of raspberry.

Preparation of test raw materials: extracting the above Chinese medicinal materials with 30% ethanol 10 times the weight of the raw materials for 3 times, each for 2 hr, mixing extractive solutions, concentrating, drying, adding into 1000ml deionized water, and making into suspension for test.

The test method comprises the following steps: 70 mice are taken and randomly divided into 7 groups, the mice are modeled to have low immunity, normal groups do not model, the model is successfully modeled, the administration is started, and the control group is administered with 0.2ml/20g of physiological saline. Administering 1-5 groups by intragastric administration, wherein the administration amount is 20ml/kg, continuously administering for 30 days, killing mice by cutting off blood after stopping administration for 24 hr, taking out spleen under aseptic condition, preparing spleen cell suspension with 1640 culture solution (containing 10% calf serum), adjusting the spleen cells of mice to 5 × 10⁶Cells/ml were added to a 96-well plate 100. mu.l per well in duplicate (i.e.one plus ConA and one without ConA). ConA 20. mu.l (concentration 1000. mu.g/ml), 1640 medium 80. mu.l, in a volume of from 200. mu.l per well, in 5% CO₂Culturing in 37 deg.C incubator for 72 hr, adding 3H-TdR3.7 × 10 per well 24 hr before terminating culture⁹(iucr). The cells were collected on a type 49 glass fiber filter paper using a cell harvester (TITERTEK CELL HARVESTER550), washed sequentially with distilled water, 5% triamineacetic acid, and absolute ethanol, the filter paper was dried in an incubator at 60 ℃, added to a cup containing 5ml of scintillation fluid, measured for radioactivity (cpm) by a liquid scintillation counter (BECKMEN LS 9800), and then the Stimulation Index (SI) was calculated, i.e., SI added to/not added to the ConA wells cpm.

Table 1 effect of different test drugs on splenic lymphocyte transformation in mice with low immunity.

Group of	SI
		Normal group	0.712±0.068**
Control group	0.133±0.041
		Test 1 group	2.348±0.123**
Test 2 groups	2.420±0.328**
		Test 3 groups	3.136±0.167***
Test 4 groups	2.378±0.209**
		Test 5 groups	2.442±0.194**

Note: p <0.01, P <0.001 compared to control.

Test example 2 anti-fatigue test of mouse

Test animals: kunming mouse, weight 18-20 g.

Test drugs:

The test method comprises the following steps: 60 mice were randomly divided into 6 groups, and the control group was given physiological saline 0.2ml/20 g. Administration 1-5 groups were administered by intragastric administration at an administration amount of 20ml/kg, and 1 hour after administration, the mice were quickly placed in a prepared swimming pool, and the time from the start of the mice entering the pool until they no longer swim was recorded. The results are shown in Table 2.

TABLE 2 anti-fatigue test results

Group of	Swimming time (min)
		Control group	2.3±0.7
Test 1 group	8.2±0.2**
		Test 2 groups	8.4±0.6**
Test 3 groups	11.1±0.4***
		Test 4 groups	8.6±0.8**
Test 5 groups	8.1±0.7**

Note: p <0.01, P <0.001 compared to control.

Test 3 blood enriching test

Test animals: SPF-grade kunming mice, females, body weight (20 ± 2) g.

Test drugs:

The test method comprises the following steps: SPF-grade kunming mice 70, randomly divided into 7 groups: blank control group, model group, test drug group, each group 10. And (3) intragastric administration, wherein the administration amount is 20ml/kg, and in addition to the normal group, other groups 1d bleed through the tail vein: the tail vein of the mouse was rubbed with 75% hot alcohol, the tail was trimmed at the distal end, and the amount of bleed was controlled at 0.25mL/10g in a graduated test tube containing physiological saline (37 ℃) while red blood-cell count (RBC) was measured. And after 24h of blood loss, blood is taken through orbital veins to measure RBC, and a series of traditional Chinese medicine blood deficiency symptoms such as pale skin, inappetence and the like appear in mice. The administration is started 2d after the model building, and the orbital veins of mice of 7d and 8d groups are continuously sampled with blood, and the RBC is detected.

And (3) test results: see table 3.

TABLE 3 Effect on RBC in blood-deficient mice

Note: p <0.01 compared to model group.

Preparation examples

Example 1

The preparation is prepared from the following raw materials of 40g of donkey-hide gelatin, 40g of ginseng, 40g of rose, 80g of sea buckthorn, 80g of roxburgh rose, 80g of mulberry and 80g of raspberry.

Extracting raw materials with 30% ethanol 8 times the weight of the raw materials for 3 times, each time for 2 hr, mixing extractive solutions, filtering, concentrating the filtrate, drying, adding adjuvants, and making into tablet 100.

Or soaking Ginseng radix, flos Rosae Rugosae, fructus Hippophae, fructus Rosae Normalis, Mori fructus, and Rubi fructus in 6000ml dry red wine for 10 hr, and filtering; melting colla Corii Asini with purified water to obtain colla Corii Asini solution; and finally, adding donkey-hide gelatin solution, 200ml of blueberry concentrated juice, 320g of xylitol and 0.95g of aspartame into the wine, uniformly stirring, filtering, adding water for injection to 10000ml, and filling into 750ml wine bottles.

Example 2

The preparation is prepared from the following raw materials of 60g of donkey-hide gelatin, 60g of ginseng, 60g of rose, 120g of sea buckthorn, 120g of roxburgh rose, 120g of mulberry and 120g of raspberry.

Example 3

The preparation is prepared from the following raw materials of 50g of donkey-hide gelatin, 50g of ginseng, 50g of rose, 100g of sea buckthorn, 100g of roxburgh rose, 100g of mulberry and 100g of raspberry.

Extracting raw materials with 30% ethanol 8 times the weight of the raw materials for 3 times, each for 2 hr, mixing extractive solutions, filtering, concentrating the filtrate, drying, adding adjuvants, and making into capsule of 100 granules.

Example 4

The preparation is prepared from the following raw materials of 45g of donkey-hide gelatin, 50g of ginseng, 45g of rose, 85g of sea buckthorn, 100g of roxburgh rose, 100g of mulberry and 90g of raspberry.

Example 5

The preparation is prepared from the following raw materials of 55g of donkey-hide gelatin, 60g of ginseng, 50g of rose, 110g of sea buckthorn, 105g of roxburgh rose, 105g of mulberry and 120g of raspberry.

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.

Claims

1. The pharmaceutical composition is characterized in that the pharmaceutical composition is prepared into a pharmaceutical preparation, wherein the pharmaceutical preparation is prepared from the following raw materials: colla Corii Asini, Ginseng radix, flos Rosae Rugosae, fructus Hippophae, fructus Rosae Normalis, Mori fructus, and Rubi fructus;

wherein the donkey-hide gelatin is 4-6 parts by weight, the ginseng is 4-6 parts by weight, the rose is 4-6 parts by weight, the sea buckthorn is 8-12 parts by weight, the rosa roxburghii is 8-12 parts by weight, the mulberry is 8-12 parts by weight, and the raspberry is 8-12 parts by weight.

2. The pharmaceutical composition according to claim 1, wherein the donkey-hide gelatin is 5 parts by weight, the ginseng is 5 parts by weight, the rose is 5 parts by weight, the sea buckthorn is 10 parts by weight, the rosa roxburghii is 10 parts by weight, the mulberry is 10 parts by weight, and the raspberry is 10 parts by weight.

3. A pharmaceutical composition according to claim 1 or 2, wherein the pharmaceutical composition is used for preparing a medicament or food for enhancing immunity.

4. A pharmaceutical composition according to claim 1 or 2, wherein the pharmaceutical composition is for use in the preparation of a hematinic drug or food.

5. A pharmaceutical composition according to claim 1 or 2, characterized by the use of a pharmaceutical composition for the preparation of an antifatigue medicament or a food product.

6. A pharmaceutical composition according to claim 1, wherein the pharmaceutical formulation comprises an oral formulation.

7. A pharmaceutical composition according to claim 1, wherein the pharmaceutical formulation comprises a wine.

8. A pharmaceutical composition according to claim 7, wherein the preparation of the wine is: