Rhodiola rosea composition as well as preparation method and application thereof

Abstract

The invention discloses a rhodiola rosea composition as well as a preparation method and application thereof, and belongs to the technical field of Tibetan medicines. The preparation method comprises the following steps: S01, mixing the milk, the rhodiola rosea polysaccharide and the gelatin according to a mass ratio of 10: 1: 2, heating and dissolving, adding the medicine core, and carrying out an ultrasonic reaction; a medicine-containing colloidal solution is obtained; s02, a sodium alginate solution with the mass concentration being 1-2% is prepared, the pH is adjusted to be 5-6, and the sodium alginate solution is obtained after ultrasonic dissolution; s03, adding the drug-containing colloidal solution into the sodium alginate solution according to the mass ratio of 1: (5-10), and performing high-speed homogenization to obtain an emulsion; and S04, dropwise adding the emulsion into a CaCl2 solution, stirring while dropwise adding, stirring for at least 1 hour after dropwise adding, filtering, washing, and drying to obtain the rhodiola rosea composition. The bilobalide injection has a remarkable effect of treating cerebral apoplexy, and the treatment effect of the bilobalide injection is slightly superior to that of a positive control drug bilobalide injection.

Description

TECHNICAL FIELD

[0001] The present application relates to a rhodiola composition and a preparation method and application thereof, and belongs to the technical field of Tibetan medicine. BACKGROUND

[0002] CN 120661556 A, an extract for preventing and treating ischemic stroke extracted from rhodiola rosea, discloses the following: dry rhodiola rosea raw materials are obtained, the raw materials are subjected to crushing treatment; an ethanol solution is used to extract the crushed raw materials to obtain an extract liquid; the extract liquid is subjected to concentration treatment to obtain a extract residue; the extract residue is dissolved in water and subjected to separation treatment to obtain a supernatant; the supernatant is subjected to pH adjustment; the supernatant after pH adjustment is subjected to adsorption purification treatment to obtain an eluate; and the eluate is subjected to concentration and drying treatment to obtain the extract. The problems of low extraction efficiency and low purity are solved. The surface area is increased by crushing the rhizome, 70% ethanol is used for reflux extraction twice, each for 2 hours, the dissolution efficiency of the target substance is improved. The extract residue is obtained by recovering ethanol under reduced pressure, dissolved in water and left to stand for 12-24 hours to remove insoluble substances, and the supernatant is obtained by centrifugation. Adjusting the pH to 5-6 is conducive to the adsorption of the target substance by the macroporous adsorption resin. Gradient elution is used, and the resin column is eluted with water, 30% ethanol and 70% ethanol in sequence to remove impurities and purify the target substance. Finally, the ethanol is recovered under reduced pressure and vacuum dried to obtain a high-purity extract with a rhodiolos content of not less than 5% and a total flavonoid content of not less than 10%. The extraction efficiency and purity of the effective components of rhodiola rosea are improved, and high-quality raw materials are provided for the prevention and treatment of ischemic stroke. The bioactivity database matching shows that the extract can inhibit IL-6 and TNF-α inflammatory factors, and the target point of ischemic stroke is consistent to 82%.

[0003] It can be seen from the above that the prior art only proves that the rhodiola extract has the effect of treating ischemic stroke by using bioactivity database matching, and the actual treatment effect is unknown. Moreover, the extract in the prior art does not contain rhodiola polysaccharide, and in the process of preparation, a sugar taste corrector needs to be added to alleviate the bitter taste of rhodiola, which undoubtedly increases the sugar metabolism burden of stroke rehabilitation patients. In addition, the function of rhodiola polysaccharide is not fully played in the prior art, the flavonoid compounds in the extract are not protected, and it is difficult to fully play its treatment effect. SUMMARY

[0004] In order to solve the above problems, the present application provides a rhodiola composition, which has a significant effect of treating stroke.

[0005] Meanwhile, the application provides a preparation method of the rhodiola rosea composition, in which rhodiolos, tyrosol, salidroside and rhodiola polysaccharide are compounded, the components in the specific proportion and the preparation method can make the effect of treating stroke of rhodiola rosea optimal, and the treatment effect is slightly better than that of ginkgo biloba injection as a positive control drug.

[0006] Meanwhile, the application provides an application of the rhodiola rosea composition in preparation of a drug for treating stroke.

[0007] To solve the above technical problems, the application adopts the technical scheme of: The rhodiola rosea composition comprises a medicine core of rhodiolos, tyrosol and salidroside in a mass ratio of 3:2:1, and the medicine core is embedded with a rhodiola polysaccharide shell outside.

[0008] The preparation method of the rhodiola rosea composition comprises the following steps: S01, milk, rhodiola polysaccharide and gelatin are mixed in a mass ratio of 10:1:2, and after being dissolved by heating at 70-80 DEG C, a medicine core is added, the addition amount of the medicine core is 0.5-1.5 times the mass of the rhodiola polysaccharide, and ultrasonic reaction is carried out at 200-300 W for at least 30 min; a medicine-containing colloidal solution is obtained; S02, a sodium alginate solution with a mass concentration of 1-2% is prepared by using deionized water, the pH value is adjusted to 5-6, and after ultrasonic dissolution, a sodium alginate solution is obtained; S03, the medicine-containing colloidal solution is added to the sodium alginate solution in a mass ratio of 1:(5-10), and after high-speed homogenization at least 10000 rpm for at least 30 s, an emulsion is obtained; S04, the emulsion is added dropwise into a CaCl2 solution with a mass concentration of 1-3%, the mass ratio of the emulsion to the CaCl2 solution is 1:(2-3), stirring is carried out while adding, the stirring speed is 800-1500 rpm, after the addition is completed, the stirring is continuously carried out for at least 1 h, after filtration, washing is carried out by using deionized water, and after drying, the rhodiola rosea composition is obtained.

[0009] Preferably, in the application, the rhodiolos, tyrosol, salidroside and rhodiola polysaccharide are all commercially available products. In the application, the rhodiolos, tyrosol, salidroside and rhodiola polysaccharide are all extracted from Rhodiola sacra.

[0010] Preferably, in S04, the drying is freeze-drying.

[0011] Preferably, in S04, the filtration process is centrifugation at least 10000 rpm for at least 5 min.

[0012] The application of the rhodiola rosea composition in preparation of a drug for treating stroke.

[0013] A drug for treating stroke, which comprises a rhodiola composition as an active ingredient and pharmaceutically acceptable excipients, and is prepared into a pharmaceutically acceptable dosage form.

[0014] Preferably, the excipients include any one or more of solvents, propellants, solubilizers, co-solvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, tonicity agents, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesion agents, integrating agents, penetration enhancers, pH regulators, buffers, plasticizers, surfactants, antifoaming agents, thickening agents, inclusion agents, humectants, absorbents, diluents, flocculants, deflocculants, filter aids, release retardants.

[0015] Preferably, the dosage form includes tablets, capsules and oral liquids.

[0016] The innovation and benefits of the present application are as follows: The rhodiola composition of the present application has a significant effect on treating stroke, and the treatment effect is slightly better than that of the positive control drug ginkgo biloba extract injection. The preparation method of the present application combines rhodiolos, tyrosol, salidroside and rhodiola polysaccharide, and the specific proportions of the components and the specific preparation method can optimize the effect of rhodiola on treating stroke, and fill the test blank for the synergistic treatment of rhodiola polysaccharide on stroke. DETAILED DESCRIPTION

[0017] The present application will be further described in detail below in combination with specific examples. The following examples are only used to illustrate the present application and not to limit the scope of the present application. Example 1

[0018] A rhodiola composition, which comprises a drug core of rhodiolos, tyrosol and salidroside in a mass ratio of 3:2:1, and a rhodiola polysaccharide shell embedded outside the drug core.

[0019] A preparation method of a rhodiola composition, comprising the following steps: S01, milk, rhodiola polysaccharide and gelatin are mixed in a mass ratio of 10:1:2, heated and dissolved at 75 DEG C, then a drug core is added, the addition amount of the drug core is 1 times the mass of the rhodiola polysaccharide, and ultrasonic reaction is carried out at 250 W for 30 min; a drug-containing colloidal solution is obtained; S02, a sodium alginate solution with a mass concentration of 1.5% is prepared by using deionized water, the pH value is adjusted to 5.7, and ultrasonic dissolution is carried out to obtain a sodium alginate solution; S03, the drug-containing colloidal solution is added to the sodium alginate solution in a mass ratio of 1:8, and after high-speed homogenization at 10000 rpm for 30 s, an emulsion is obtained; S04, the emulsion is dropped into a 2% CaCl2 solution drop by drop, the mass ratio of the emulsion to the CaCl2 solution is 1:2.5, stirring is performed while dropping, the stirring speed is 1000 rpm, after the dropping is completed, stirring is continuously performed for 1 h, after centrifugation at 10000 rpm for 5 min, washing is performed with deionized water, and after freeze-drying, the Rhodiola rosea composition is obtained.

[0020] The application of the Rhodiola rosea composition of the embodiment in the preparation of a drug for treating stroke.

[0021] The drug for treating stroke of the embodiment contains the Rhodiola rosea composition as an active ingredient and pharmaceutically acceptable excipients, and is prepared into a pharmaceutically acceptable dosage form.

[0022] Preferably, the excipients include any one or more of solvents, propellants, solubilizers, co-solvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavorings, preservatives, suspending agents, coating materials, fragrances, anti-adhesion agents, integrating agents, penetration enhancers, pH regulators, buffers, plasticizers, surfactants, antifoaming agents, thickening agents, inclusion agents, humectants, absorbents, diluents, flocculants, deflocculants, filtration aids, release retardants.

[0023] Preferably, the dosage form includes tablets, capsules and oral liquids.

[0024] The pharmacological test of the Rhodiola rosea composition of the embodiment in treating stroke is as follows: Animals: male C57BL / 6 mice (8-12 weeks old, weighing 22-28 g). Raising environment: temperature 22°C±3°C, humidity 60%±5%, 12 / 12h light / dark cycle. Before the experiment, the animals in each group were allowed to freely eat and drink, and all the animals were adapted to the environment for at least 3 days. All the animals were raised and experimented by the animal management committee of the Second Hospital of Hebei Medical University, and met the standards (license number: HMUSHC-130318).

[0025] Stroke model: a modified Longa thread embolism method was used to prepare a stroke model (i.e. a cerebral ischemia-reperfusion injury model, the thread embolism was slowly pulled out to restore perfusion after blood flow was blocked for 1-2 hours).

[0026] At 24h after the operation, the neurological deficits of the mice in each group were scored and determined, a modified Longa grading method was used for single-blind behavioral scoring, specifically: 0 points: no defects; 1 point: the mouse cannot stretch the contralateral forelimb; 2 points: the mouse flexes the contralateral forelimb; 3 points: the mouse slightly circles to the contralateral side; 4 points: the mouse seriously circles to the contralateral side; 5 points: the mouse falls to the contralateral side.

[0027] The drug was administered by gavage once a day for three consecutive days before ischemia-reperfusion.

[0028] Mouse grouping: Sham operation group (n=6): The mice in this group did not undergo cerebral ischemia-reperfusion injury operation; the drug was a polybutylene succinate solution containing 0.1% DMSO, and the dosage was 30 mg / kg.

[0029] Stroke group (n=6): The mice in this group underwent cerebral ischemia-reperfusion injury operation; the drug was a polybutylene succinate solution containing 0.1% DMSO, and the dosage was 30 mg / kg.

[0030] Positive drug control group (n=6): The mice in this group underwent cerebral ischemia-reperfusion injury operation; the drug was a 30 mg / kg ginkgo lactone injection.

[0031] Low-dose rhodiola composition intervention group (n=6): The mice in this group underwent cerebral ischemia-reperfusion injury operation; the drug was a 10 mg / kg rhodiola composition of the present embodiment.

[0032] Medium-dose rhodiola composition intervention group (n=6): The mice in this group underwent cerebral ischemia-reperfusion injury operation; the drug was a 20 mg / kg rhodiola composition of the present embodiment.

[0033] High-dose rhodiola composition intervention group (n=6): The mice in this group underwent cerebral ischemia-reperfusion injury operation; the drug was a 30 mg / kg rhodiola composition of the present embodiment.

[0034] Comparison experiment one group (n=6): The mice in this group underwent cerebral ischemia-reperfusion injury operation; the drug was a 20 mg / kg rhodiola composition, in which the core ingredient was rhodiolos, tyrosol, and salidroside in a mass ratio of 4:2:1, and the rest was the same as in the present embodiment 1.

[0035] Comparison experiment two group (n=6): The mice in this group underwent cerebral ischemia-reperfusion injury operation; the drug was a 20 mg / kg rhodiola composition, in which the core ingredient was rhodiolos, tyrosol, and salidroside in a mass ratio of 3:3:1, and the rest was the same as in the present embodiment 1.

[0036] Comparison experiment three group (n=6): The mice in this group underwent cerebral ischemia-reperfusion injury operation; the drug was a 20 mg / kg rhodiola composition, in which the core ingredient was rhodiolos, tyrosol, and salidroside in a mass ratio of 3:2:2, and the rest was the same as in the present embodiment 1.

[0037] Four comparative experimental groups (n=6): Mice in this group underwent cerebral ischemia-reperfusion injury surgery; they were administered 20 mg / kg of Rhodiola rosea composition, in which Rhodiola rosea polysaccharide was replaced with dextran, and the rest of the contents were the same as in Example 1.

[0038] The fifth group of comparative experiments (n=6) involved mice undergoing cerebral ischemia-reperfusion injury surgery and were administered 20 mg / kg of a Rhodiola rosea composition, which consisted of rhodioloside, tyrosol, rhodioloside and rhodiola polysaccharide in a mass ratio of 3:2:1:6, and was administered directly.

[0039] After being administered the drugs according to the above grouping, mice underwent cerebral ischemia-reperfusion injury surgery. The extent of neurological dysfunction in each group was observed and scored. The specific results are shown in Table 1 below.

[0040] Table 1

[0041] As shown in Table 1, the medium-dose Rhodiola rosea composition in this embodiment is slightly more effective than Ginkgo biloba extract injection in treating stroke.

[0042] Example 2

[0043] The only difference between this embodiment and Embodiment 1 is that: A method for preparing a Rhodiola rosea composition includes the following steps: S01, mix milk, Rhodiola rosea polysaccharide and gelatin in a mass ratio of 10:1:2, heat to 70℃ to dissolve, add drug core, the amount of drug core added is 0.5 times the mass of Rhodiola rosea polysaccharide, sonicate at 200W for 60 min; obtain drug-containing colloidal solution; SO2, prepare a sodium alginate solution with a mass concentration of 1.0% using deionized water, adjust the pH to 5.0, and dissolve it by sonication to obtain the sodium alginate solution; S03, the drug-containing colloidal solution was added to the sodium alginate solution at a mass ratio of 1:5, and after high-speed homogenization at 12000 rpm for 45 seconds, an emulsion was obtained; S04, the emulsion was added dropwise to a 1% CaCl2 solution at a mass ratio of 1:2, while stirring at 800 rpm. After the addition was complete, stirring was continued for 2 hours. After centrifugation at 12000 rpm for 10 minutes, the emulsion was washed with deionized water and freeze-dried to obtain the Rhodiola rosea composition.

[0044] Example 3

[0045] The only difference between this embodiment and Embodiment 1 is that: A method for preparing a Rhodiola rosea composition includes the following steps: S01, milk, rhodiola polysaccharide and gelatin are mixed according to the mass ratio of 10:1:2, heated and dissolved at 80 DEG C, then the drug core is added, the addition amount of the drug core is 1.5 times of the mass of rhodiola polysaccharide, and ultrasonic reaction is carried out at 300W for 45min; a drug-containing colloidal solution is obtained; S02, a sodium alginate solution with a mass concentration of 2.0% is prepared by using deionized water, the pH is adjusted to 6.0, and ultrasonic dissolution is carried out to obtain a sodium alginate solution; S03, the drug-containing colloidal solution is added to the sodium alginate solution according to the mass ratio of 1:10, and after high-speed homogenization at 10000rpm for 30s, an emulsion is obtained; S04, the emulsion is added dropwise into a CaCl2 solution with a mass concentration of 3%, and the mass ratio of the emulsion to the CaCl2 solution is 1:3, stirring is carried out at the same time, the stirring speed is 1500rpm, after the addition is completed, stirring is continued for 1h, centrifugation is carried out at 10000rpm for 6min, then deionized water is used for washing, and after freeze-drying, a rhodiola composition is obtained.

[0046] Example 4

[0047] The difference between this embodiment and example 1 is only that: A preparation method of a rhodiola composition comprises the following steps: S01, milk, rhodiola polysaccharide and gelatin are mixed according to the mass ratio of 10:1:2, heated and dissolved at 75 DEG C, then the drug core is added, the addition amount of the drug core is 1.2 times of the mass of rhodiola polysaccharide, and ultrasonic reaction is carried out at 300W for 60min; a drug-containing colloidal solution is obtained; S02, a sodium alginate solution with a mass concentration of 2.0% is prepared by using deionized water, the pH is adjusted to 5.5, and ultrasonic dissolution is carried out to obtain a sodium alginate solution; S03, the drug-containing colloidal solution is added to the sodium alginate solution according to the mass ratio of 1:6, and after high-speed homogenization at 15000rpm for 30s, an emulsion is obtained; S04, the emulsion is added dropwise into a CaCl2 solution with a mass concentration of 3%, and the mass ratio of the emulsion to the CaCl2 solution is 1:2, stirring is carried out at the same time, the stirring speed is 1500rpm, after the addition is completed, stirring is continued for 1h, centrifugation is carried out at 15000rpm for 8min, then deionized water is used for washing, and after freeze-drying, a rhodiola composition is obtained.

[0048] Example 5

[0049] The difference between this embodiment and example 1 is only that: A preparation method of a rhodiola composition comprises the following steps: S01, milk, rhodiola polysaccharide and gelatin are mixed according to the mass ratio of 10:1:2, heated and dissolved at 70°C, then the drug core is added, the addition amount of the drug core is 0.8 times of the mass of rhodiola polysaccharide, and ultrasonic reaction is carried out at 200W for 30min; a drug-containing colloidal solution is obtained; S02, a sodium alginate solution with a mass concentration of 1.0% is prepared with deionized water, the pH is adjusted to 5.7, and the sodium alginate solution is obtained after ultrasonic dissolution; S03, the drug-containing colloidal solution is added to the sodium alginate solution according to the mass ratio of 1:7, and an emulsion is obtained after high-speed homogenization at 10000rpm for 30s; S04, the emulsion is added dropwise into a CaCl2 solution with a mass concentration of 2%, the mass ratio of the emulsion to the CaCl2 solution is 1:3, stirring is carried out while dropping, the stirring speed is 1000rpm, after the dropping is completed, the stirring is continued for 3h, then centrifugation is carried out at 10000rpm for 10min, then washing is carried out with deionized water, and then freeze-drying is carried out, and thus a rhodiola composition is obtained.

[0050] It should be understood that in order to simplify the present disclosure and to help understand one or more of the various inventive aspects, various features of the present application have sometimes been grouped together in a single embodiment or described in a description thereof. However, the method of this disclosure should not be interpreted to reflect an intention that the claimed application requires more features than are explicitly recited in each claim. Rather, the inventive aspects are defined solely by the claims, as reflected in the claims section. Thus, the claims at the end of the detailed description are hereby expressly incorporated into this detailed description by this specific incorporation by reference, wherein each claim is independently a separate embodiment of the application.

[0051] Although the present application has been described in terms of limited embodiments, those skilled in the art will appreciate that other embodiments are possible, within the scope of the application described herein, as the skilled person will appreciate from the above description. Furthermore, it should be noted that the language used in the specification has been chosen primarily for readability and instructional purposes and can not have been selected to convey an exclusive or exhaustive meaning. Therefore, many modifications and variations of the present application are possible in light of the above teachings without departing from the scope and spirit of the appended claims. The disclosure of the application is illustrative only and not limiting of the scope of the application, which is defined by the claims.

[0052] The above only describes the preferred embodiments of the present application, and it should be pointed out that those skilled in the art can make several improvements and refinements without departing from the principles of the present application, and these improvements and refinements should also be considered as the protection scope of the present application.

Claims

1. A Rhodiola rosea composition, characterized in that, The core consists of rhodioloside, tyrosol, and rhodioloside in a mass ratio of 3:2:1, and is encapsulated with a rhodiola polysaccharide shell.

2. The method for preparing a Rhodiola rosea composition according to claim 1, characterized in that, Includes the following steps: S01, mix milk, Rhodiola rosea polysaccharide and gelatin in a mass ratio of 10:1:2, heat to 70~80℃ to dissolve, add drug core, the amount of drug core added is 0.5~1.5 times the mass of Rhodiola rosea polysaccharide, sonicate at 200~300W for at least 30 minutes; to obtain drug-containing colloidal solution; SO2 is prepared by using deionized water to prepare a sodium alginate solution with a mass concentration of 1-2%, adjusting the pH to 5-6, and then dissolving it by ultrasonication to obtain the sodium alginate solution. S03, add the drug-containing colloidal solution to the sodium alginate solution at a mass ratio of 1: (5~10), and homogenize at high speed at at least 10000 rpm for at least 30 seconds to obtain an emulsion; S04, the emulsion is added dropwise to a CaCl2 solution with a mass concentration of 1~3%, and the mass ratio of the emulsion to the CaCl2 solution is 1:(2~3). The mixture is stirred while adding the emulsion, and the stirring speed is 800~1500 rpm. After the addition is complete, the mixture is stirred for at least 1 hour. After filtration, the mixture is washed with deionized water and dried to obtain the Rhodiola rosea composition.

3. The preparation method according to claim 2, characterized in that, In S04, drying is freeze drying.

4. The preparation method according to claim 2, characterized in that, In S04, the filtration process is as follows: centrifugation at at least 10,000 rpm for at least 5 minutes.

5. The use of the Rhodiola rosea composition according to claim 1 in the preparation of a drug for treating stroke.

6. A drug for treating stroke, characterized in that, Using the Rhodiola rosea composition of claim 1 as the active ingredient, and further containing pharmaceutically acceptable excipients, a pharmaceutically acceptable dosage form is prepared.

7. A drug for treating stroke according to claim 5, characterized in that, Dosage forms include tablets, capsules, and oral solutions.

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