A saponin composition for treating insomnia

Abstract

This invention provides a saponin composition for treating insomnia, comprising jujube seed saponin A, ginsenoside Rb1, and gypenosides XLIX as active ingredients, and a pharmaceutically acceptable carrier; wherein the weight ratio of jujube seed saponin A to gypenosides XLIX is 1:2-6; and / or, the weight ratio of ginsenoside Rb1 to gypenosides XLIX is 1:2-8. Research results show that a composition of a certain proportion of jujube seed saponin A and gypenosides XLIX has a synergistic effect in upregulating the level of γ-aminobutyric acid in brain tissue; a composition of a certain proportion of gypenosides XLIX and ginsenoside Rb1 has a synergistic effect in upregulating the level of serotonin in brain tissue. Therefore, the saponin composition provided by this invention can effectively treat and / or prevent insomnia.

Description

Technical Field

[0001] This invention relates to the field of biomedicine, specifically to a saponin composition having therapeutic and / or preventive effects on insomnia, the saponin composition comprising jujube seed saponin A, gypenosides XLIX and ginsenoside Rb1. Background Technology

[0002] Insomnia is a common phenomenon in people's lives. With the fast pace of modern life, the incidence of sleep disorders is increasing year by year. The consensus on insomnia is that chronic insomnia occurs at least three times a week and lasts for at least three months. Currently, the global prevalence of insomnia is estimated to be between 10% and 40%. Short-term insomnia can make people look haggard and mentally exhausted. With increasing life pressure, the number of people suffering from insomnia is gradually increasing and trending towards younger ages. Insomnia can lead to various chronic diseases such as cardiovascular and cerebrovascular diseases, diabetes, mental disorders, and depression, and can also affect the recovery of some existing diseases. Therefore, good sleep is an important condition for maintaining good physical condition. Currently, the treatment of insomnia still relies on sleeping pills such as benzodiazepines. (BZD) derivatives and barbiturates are first-line drugs for treating insomnia. These drugs are effective, but have significant side effects, and long-term use can lead to dependence. Therefore, the development of naturally derived compositions with therapeutic effects on insomnia is receiving increasing attention.

[0003] Jujube seed saponin A can be extracted from the dried mature seeds of jujube (Ziziphus jujuba Mill. var. spinosa (Bunge), a plant in the Rhamnaceae family. Modern research suggests that jujube seed saponin A is the active ingredient of jujube seed and has strong sedative and hypnotic effects.

[0004] Gynostemma pentaphyllum saponin XLIX can be extracted from the stems and leaves of Gynostemma pentaphyllum, a plant in the Cucurbitaceae family. It belongs to the dammarane-type tetracyclic triterpenoid saponin and has been shown to have central nervous system depressant effects.

[0005] Ginsenoside Rb1 can be extracted from plants of the Araliaceae family such as ginseng, Panax notoginseng, and American ginseng. Studies have reported that it has a good effect on improving sleep.

[0006] Currently, most reports on compositions for improving sleep involve traditional Chinese medicines with sleep-improving functions. There are no reports on the effects and synergistic effects of combinations of monomeric substances from different types of plants in treating insomnia. Summary of the Invention

[0007] The purpose of this invention is to provide a saponin composition that has a synergistic effect in upregulating the level of γ-aminobutyric acid in brain tissue, a saponin composition that has a synergistic effect in upregulating the level of 5-hydroxytryptamine in brain tissue, and a saponin composition that has the effect of treating and / or preventing insomnia.

[0008] Through extensive experimental research, the inventors verified the sleep-improving function of various saponins in mice by combining two saponins. The results showed that the combination of a certain proportion of jujube seed saponin A and gypenosides XLIX had a synergistic effect in upregulating the level of γ-aminobutyric acid in brain tissue; and the combination of a certain proportion of gypenosides XLIX and ginsenoside Rb1 had a synergistic effect in upregulating the level of 5-hydroxytryptamine in brain tissue.

[0009] That is, the present invention includes:

[0010] 1. A saponin composition capable of upregulating γ-aminobutyric acid (GABA) levels in brain tissue, comprising jujuboside A and gypenosides XLIX as active ingredients, and a pharmaceutically acceptable carrier; wherein,

[0011] The weight ratio of jujube seed saponin A to gypenosides XLIX is 1:2 to 6.

[0012] 2. The saponin composition according to claim 1, wherein,

[0013] The weight ratio of jujube seed saponin A to gypenosides XLIX is 1:3 to 5.

[0014] 3. The saponin composition according to claim 1, wherein,

[0015] The jujube seed saponin A and gypenosides XLIX are the only active ingredients that can upregulate the level of γ-aminobutyric acid in brain tissue.

[0016] 4. A saponin composition capable of upregulating serotonin levels in brain tissue, comprising ginsenoside Rb1 and gypenosides XLIX as active ingredients, and a pharmaceutically acceptable carrier; wherein,

[0017] The weight ratio of ginsenoside Rb1 to gypenosides XLIX is 1:2 to 8.

[0018] 5. The saponin composition according to claim 4, wherein,

[0019] The weight ratio of ginsenoside Rb1 to gypenosides XLIX is 1:3 to 5.

[0020] 6. The saponin composition according to claim 4, wherein,

[0021] The ginsenoside Rb1 and gypenosides XLIX are the only active ingredients that can upregulate 5-hydroxytryptamine levels in brain tissue.

[0022] 7. A saponin composition for treating and / or preventing insomnia, comprising jujube seed saponin A, ginsenoside Rb1, and gypenosides XLIX as active ingredients, and a pharmaceutically acceptable carrier; wherein,

[0023] The weight ratio of jujube seed saponin A to gypenosides XLIX is 1:2-6; and / or,

[0024] The weight ratio of ginsenoside Rb1 to gypenosides XLIX is 1:2 to 8.

[0025] 8. The saponin composition according to item 7, wherein,

[0026] The weight ratio of jujube seed saponin A to gypenosides XLIX is 1:3-5; and / or,

[0027] The weight ratio of ginsenoside Rb1 to gypenosides XLIX is 1:3 to 5.

[0028] 9. The saponin composition according to item 7, wherein the jujube seed saponin A and gypenosides XLIX are the only active ingredients that can upregulate the level of γ-aminobutyric acid in brain tissue; and / or the ginsenoside Rb1 and gypenosides XLIX are the only active ingredients that can upregulate the level of 5-hydroxytryptamine in brain tissue.

[0029] 10. Use of a saponin composition comprising jujube seed saponin A, ginsenoside Rb1, and gypenosides XLIX in the preparation of a medicament for treating and / or preventing insomnia; wherein, in the saponin composition,

[0030] The weight ratio of jujube seed saponin A to gypenosides XLIX is 1:2 to 6, preferably 1:3 to 5; and / or,

[0031] The weight ratio of ginsenoside Rb1 to gypenosides XLIX is 1:2 to 8, preferably 1:3 to 5.

[0032] 11. A method for treating and / or preventing insomnia, comprising the step of administering the saponin composition of any one of items 1 to 9 to a subject.

[0033] The saponin compositions of the present invention can be, for example, oral dosage forms or injections. The oral dosage forms can be, for example, hard capsules, soft capsules, controlled-release capsules, sugar-coated tablets, powders, granules, drop pills, water-honey pills, syrups, or oral liquids; the injections can be solutions, suspensions, emulsions, or lyophilized powders. The saponin compositions of the present invention may contain excipients or other pharmaceutically acceptable carriers. The excipients can be, for example, one or more of sodium hyaluronate, sodium alginate, chitosan, or collagen.

[0034] Detailed Implementation of the Invention

[0035] The present invention will now be described in detail with reference to specific embodiments. Unless otherwise specified, the scientific terms used in this specification have the meanings commonly understood by those skilled in the art; in case of conflict, the definitions in this specification shall prevail.

[0036] Firstly, in one aspect, the present invention provides a saponin composition (saponin composition 1) that can upregulate the level of γ-aminobutyric acid in brain tissue, comprising jujuboside A and gypenosides XLIX as active ingredients, and a pharmaceutically acceptable carrier; wherein the weight ratio of jujuboside A to gypenosides XLIX is 1:2 to 6.

[0037] In this specification, jujube seed saponin A refers to the compound described in chemical formula 1 below.

[0038]

Chemical Formula 1

[0039]

[0040] The above-mentioned jujube seed saponin A is a known compound and can be prepared using methods known in this technical field. For example, jujube seed saponin A can be prepared by separating and purifying total jujube seed saponins from jujube seed extract.

[0041] In this specification, Gynostemma pentaphyllum saponin XLIX refers to the compound described in Chemical Formula 2 below.

[0042] [Chemical Formula 2]

[0043]

[0044] The above-mentioned Gynostemma pentaphyllum saponin XLIX is a known compound and can be prepared using methods known in this technical field. For example, Gynostemma pentaphyllum saponin XLIX can be prepared by separating and purifying total Gynostemma pentaphyllum saponins from Gynostemma pentaphyllum extract.

[0045] Furthermore, in one aspect, the present invention also provides a saponin composition (saponin composition 2) that can upregulate the level of 5-hydroxytryptamine in brain tissue, comprising ginsenoside Rb1 and gypenosides XLIX as active ingredients, and a pharmaceutically acceptable carrier; wherein the weight ratio of ginsenoside Rb1 to gypenosides XLIX is 1:2 to 8.

[0046] In this specification, ginsenoside Rb1 refers to the compound described in chemical formula 3 below.

[0047]

Chemical Formula 3

[0048]

[0049] The aforementioned ginsenoside Rb1 is a known compound and can be prepared using methods known in this technical field. For example, ginsenoside Rb1 can be prepared by separating and purifying total saponins from Panax notoginseng, American ginseng, or ginseng extracts.

[0050] Furthermore, in one aspect, the present invention also provides a saponin composition for treating and / or preventing insomnia, comprising jujuboside A, ginsenoside Rb1, and gypenosides XLIX as active ingredients, and a pharmaceutically acceptable carrier; wherein the weight ratio of jujuboside A to gypenosides XLIX is 1:2 to 6; and / or, the weight ratio of ginsenoside Rb1 to gypenosides XLIX is 1:2 to 8.

[0051] The saponin compositions 1-3 may contain other ingredients for treating and / or preventing insomnia, or they may not contain other ingredients for treating and / or preventing insomnia (i.e., using jujube seed saponin A, gypenosides XLIX, and ginsenoside Rb1 as the sole active ingredients for treating and / or preventing insomnia). When the saponin compositions 1-3 contain other ingredients for treating and / or preventing insomnia, from the perspective of better exerting synergistic effects, the content of the three saponins—jujube seed saponin A, gypenosides XLIX, and ginsenoside Rb1—is preferably 50 parts by weight or more, more preferably 60 parts by weight or more, more preferably 70 parts by weight or more, more preferably 80 parts by weight or more, more preferably 90 parts by weight or more, more preferably 95 parts by weight or more, more preferably 99 parts by weight or more, and more preferably 100 parts by weight (i.e., the saponin compositions 1-3 contain only these three ingredients for treating and / or preventing insomnia), with 100 parts by weight representing all the ingredients for treating and / or preventing insomnia contained in the pharmaceutical composition. The purity of jujube seed saponin A, gypenosides XLIX, and ginsenoside Rb1 in the saponin compositions 1-3 can be above 98%, 98%, and 98%, respectively.

[0052] The contents of jujube seed saponin A, gypenosides XLIX and ginsenoside Rb1 can all be determined by HPLC.

[0053] The saponin compositions 1-3 may contain pharmaceutically acceptable carriers, such as excipients. There are no particular limitations on the excipients used in the saponin compositions 1-3; for example, excipients commonly used in pharmaceuticals or health products in this technical field can be used. Specifically, the excipients may be, for example, starch, dextrin, lactose, mannitol, sodium hydroxypropyl methylcellulose, xanthan gum, protein sugar, etc.

[0054] There are no particular limitations on the dosage form of the saponin compositions 1-3, for example, they can be oral or injectable dosage forms. The oral dosage form can be a liquid or a solid dosage form. The oral dosage form can be, for example, hard capsules, soft capsules, controlled-release capsules, tablets, sugar-coated tablets, powders, granules, drop pills, water-honey pills, syrups, or oral liquids; the injectable dosage form can be, for example, a solution, suspension, emulsion, or lyophilized powder. The administration route of the saponin compositions 1-3 can be, for example, oral, intravenous drip, or injection.

[0055] When preparing oral solid dosage forms, excipients, as well as binders, disintegrants, lubricants, colorants, flavoring agents, etc., as needed, can be added to the active pharmaceutical ingredient, and then tablets, coated tablets, granules, fine granules, powders, capsules, etc. can be prepared according to conventional methods.

[0056] Excipients such as lactose, corn starch, white sugar, glucose, sorbitol, crystalline cellulose, and silicon dioxide can be used; binders such as polyvinyl alcohol, ethyl cellulose, methyl cellulose, gum arabic, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose can be used; lubricants such as magnesium stearate, talc, and silicon dioxide can be used; colorants permitted for addition to pharmaceuticals can be used; and flavoring agents such as cocoa powder, menthol, aromatic acids, peppermint oil, borneol, and cinnamon powder can be used. Of course, sugar coating, gelatin coating, and other necessary coatings can also be applied to the above-mentioned tablets and granules.

[0057] When preparing injectable formulations, pH adjusters, buffers, suspending agents, solubilizers, stabilizers, isotonic agents, preservatives, etc., can be added to the active pharmaceutical ingredient as needed, and then the formulation can be prepared for intravenous, subcutaneous, or intramuscular injection using conventional methods. Alternatively, a freeze-dried product can be prepared using conventional methods, depending on the requirements.

[0058] Examples of suspending agents include methylcellulose, Tween 80, hydroxyethylcellulose, gum arabic, tragacanth powder, sodium carboxymethyl cellulose, and polyoxyethylene sorbitol monolaurate.

[0059] Examples of solubilizers include polyethylene oxide hydrogenated castor oil, Tween 80, nicotinamide, polyoxyethylene sorbitol monolaurate, polyethylene glycol, and castor oil fatty acid ethyl ester.

[0060] In addition, examples of stabilizers include sodium sulfite and sodium metabisulfite; examples of preservatives include methylparaben, ethylparaben, sorbic acid, phenol, cresol, and chlorocresol.

[0061] Applying the saponin compositions 1 to 3 to a subject can treat and / or prevent insomnia. The subject can be a mammal, such as a human, rat, rabbit, sheep, pig, cow, cat, dog, monkey, etc., preferably a human.

[0062] The saponin compositions 1-3 can be administered orally or non-orally. The dosage varies depending on the severity of symptoms, patient age, sex, weight, sensitivity differences, method of administration, timing of administration, interval of administration, nature of the pharmaceutical preparation, and type of active ingredient, and there are no special restrictions. However, the usual dosage for adults (60 kg) is 1 μg to 30,000 mg daily, preferably 10 μg to 3,000 mg, more preferably 100 μg to 2,000 mg, more preferably 1 mg to 1,000 mg, more preferably 10 mg to 500 mg, and more preferably 100 mg to 300 mg (based on the total amount of jujube seed saponin A, gypenosides XLIX, and ginsenoside Rb1). The above dosage can usually be divided into 1 to 3 administrations per day. Example

[0063] The embodiments given below are provided to facilitate understanding of the present invention and are not intended to limit the scope of the claims in any way.

[0064] Example 1: Effects of jujuboside A, gypenosides XLIX, and a combination of jujuboside A / gypenosides XLIX on GABA levels in mouse brain tissue.

[0065] Compositions were prepared by mixing jujube seed saponin A and gypenosides XLIX in weight ratios of 1:1, 1:3, 1:5, and 1:7, and were designated as composition 1, composition 2, composition 3, and composition 4, respectively. Separate administration groups of jujube seed saponin A and gypenosides XLIX were also set up as controls.

[0066] Animal source: 180 male Kunming mice, weighing 18-22g, provided by the Animal Center of Xi'an Jiaotong University, observed for 3 days before the experiment.

[0067] Animal grouping: There were 10 experimental groups, namely, jujube seed saponin A group, gypenosides XLIX group 1, gypenosides XLIX group 2, gypenosides XLIX group 3, gypenosides XLIX group 4, combination groups 1-4, and blank control group. Each group contained 10 mice. The control group was given an equal volume of blank solution. Each mouse was gavaged with 0.2 ml / 10 g once a day for 30 consecutive days.

[0068] Instruments and reagents: Gamma-aminobutyric acid (GABA) reagent kit (Nanjing Jiancheng Biotechnology Co., Ltd.); Microplate reader (BioTek Epoch).

[0069] Experimental Methods: After 30 days of continuous gavage, animals were fasted but allowed free access to water for 1 day. The following morning, after weighing, animals were euthanized by cervical dislocation, decapitated on ice, and the brain was removed. The hypothalamus tissue was isolated, rinsed with pre-cooled physiological saline, dried with filter paper, and weighed. Nine times the volume of physiological saline was added at a body weight (g) to volume (mL) ratio of 1:9, and the tissue was homogenized using a glass homogenizer under ice-water bath conditions. Centrifugation was performed at 2500 rpm for 10 minutes at a radius of 13.5 cm. The supernatant was collected for analysis. Detection and analysis were performed according to the GABA reagent kit's operating procedures.

[0070] The drug combination index CI of the jujube seed saponin A / gynostemma pentaphyllum saponin XLIX combination was calculated as (AxB) / AB (Romanelli S, Perego P, Pratesi G, Carenini N, Tortoreto M, Zunino F. In vitro and in vivo interaction between cisplatin and topotecan in ovarian carcinoma systems.[J]. Cancer chemotherapy and pharmacology, 1998, 41(5):385-390), where T is the GABA content in the control group and C is the GABA content in each experimental group. For example, A and B are the C / T values ​​of jujube seed saponin A and different doses of gynostemma pentaphyllum saponin XLIX administered alone, and AB is the C / T value of jujube seed saponin A and gynostemma pentaphyllum saponin XLIX used in combination. When CI < 1, the two saponin combinations have a synergistic effect.

[0071] The statistical results are shown in Table 1 below:

[0072] Table 1. Effects of various saponin compositions on GABA content in mouse brain tissue (n = 10, x ± s)

[0073]

[0074] Note: The dosages of compositions 1-4 are the combined dosages of jujube seed saponin A group and gypenosides XLIX group 1-4.

[0075] As shown in Table 1, compared with the individual effects of jujube seed saponin A and the corresponding dose of gypenosides XLIX, the drug combination index (CI) values ​​of compositions 2 and 3 were all less than 1. However, the drug combination index (CI) values ​​of compositions 1 and 4 were greater than 1. This indicates that jujube seed saponin A and gypenosides XLIX can synergistically upregulate GABA levels in mouse brain tissue within a certain ratio range, thereby improving sleep. However, outside the scope of this invention, there is no synergistic effect. GABA is an inhibitory neurotransmitter that mainly exerts its sedative-hypnotic effect through its specific binding to GABA receptors (GABAA).

[0076] Example 2: Effects of ginsenoside Rb1, gypenosides XLIX, and a combination of ginsenoside Rb1 and gypenosides XLIX on 5-HT levels in mouse brain tissue.

[0077] Compositions were prepared by mixing ginsenoside Rb1 and gypenosides XLIX in weight ratios of 1:1, 1:3, 1:5, and 1:10, and were named Composition 1, Composition 2, Composition 3, and Composition 4, respectively. Separate administration groups of jujube seed saponin A and gypenosides XLIX were set as controls.

[0078] Animal source: 180 male Kunming mice, weighing 18-22g, provided by the Animal Center of Xi'an Jiaotong University, observed for 3 days before the experiment.

[0079] Animal grouping: There were 10 experimental groups in total, namely ginsenoside Rb1 group, gypenosides XLIX group 1, gypenosides XLIX group 2, gypenosides XLIX group 3, gypenosides XLIX group 4, combination groups 1-4, and blank control group. Each group contained 10 mice. The control group was given an equal volume of blank solution. Each mouse was given 0.2 ml / 10 g by gavage once a day for 30 consecutive days.

[0080] Instruments and reagents: 5-hydroxytryptamine (5-HT) kit (Nanjing Jiancheng Biotechnology Co., Ltd.); microplate reader (BioTek Epoch).

[0081] Methods: After 30 days of continuous gavage, animals were fasted but allowed free access to water for 1 day. The following morning, after weighing, animals were euthanized by cervical dislocation, decapitated on ice, and the brain was extracted. Hypothalamic tissue was isolated, rinsed with pre-cooled physiological saline, dried with filter paper, and weighed. Nine times the volume of physiological saline was added at a body weight (g) to volume (mL) ratio of 1:9, and the tissue was homogenized using a glass homogenizer under ice-water bath conditions. Centrifugation was performed at 2500 rpm for 10 minutes (13.5 cm radius), and the supernatant was collected for analysis. Detection and analysis were performed according to the 5-HT reagent kit procedure.

[0082] The drug combination index CI of the ginsenoside Rb1 / Gynostemma pentaphyllum saponin XLIX combination was calculated as (A x B) / AB, where T is the 5-HT content of the control group and C is the 5-HT content of each experimental group. For example, A and B are the C / T values ​​of ginsenoside Rb1 and different doses of Gynostemma pentaphyllum saponin XLIX administered alone, and AB is the C / T value of ginsenoside Rb1 and different doses of Gynostemma pentaphyllum saponin XLIX administered in combination. When CI < 1, the two saponin combinations have a synergistic effect.

[0083] The statistical results are shown in Table 2 below:

[0084] Table 2. Effects of various saponin compositions on 5-HT content in mouse brain tissue (n=10, x±s)

[0085]

[0086] Note: The dosages of compositions 1-4 are the combined dosages of ginsenoside Rb1 group and gypenosides XLIX group 1-4, respectively.

[0087] As shown in Table 2, compared with ginsenoside Rb1 and the corresponding dose of gypenosides XLIX acting alone, the drug combination index (CI) values ​​of compositions 2 and 3 were all less than 1. However, the drug combination index (CI) values ​​of compositions 1 and 4 were greater than 1, indicating that ginsenoside Rb1 and gypenosides XLIX can synergistically upregulate 5-HT levels in mouse brain tissue within a certain ratio range. However, outside the scope of this invention, there is no synergistic effect. 5-HT is an important monoamine neurotransmitter involved in sleep regulation; a decrease in 5-HT levels in the brain can lead to insomnia.

[0088] In summary, the combination of jujube seed saponin A and gypenosides XLIX in this invention primarily achieves its therapeutic effect on insomnia or improves sleep by upregulating GABA levels in mouse brain tissue. The combination of gypenosides XLIX and ginsenoside Rb1 primarily exerts its therapeutic effect on insomnia or improves sleep by upregulating 5-HT levels in mouse brain tissue. Therefore, the combined use of these three saponins in this invention achieves a superior therapeutic effect on insomnia. Furthermore, in all animal experiments involved in this invention, all groups of animals moved freely, and no abnormal weight, food intake, or food consumption were observed. There were no statistically significant differences compared to the control group, indicating that the combination of jujube seed saponin A, gypenosides XLIX, and ginsenoside Rb1 is safe for in vivo treatment in mice.

[0089] It should be noted that, provided it is feasible and does not significantly deviate from the spirit of the invention, any technical feature or combination of technical features described as a component of a certain technical solution in this specification can also be applied to other technical solutions; furthermore, provided it is feasible and does not significantly deviate from the spirit of the invention, the technical features described as components of different technical solutions can also be combined in any way to constitute other technical solutions. The invention also includes technical solutions obtained through combinations under the above circumstances, and these technical solutions are equivalent to those described in this specification.

[0090] The present invention has been described above through specific embodiments and examples. However, those skilled in the art should understand that these are not intended to limit the scope of the present invention, which should be determined by the claims.

[0091] Industrial applicability

[0092] This invention provides a saponin composition containing jujube seed saponin A, gypenosides XLIX and ginsenoside Rb1, which has a synergistic effect and has a therapeutic effect on insomnia.

Claims

1. A saponin composition for treating and / or preventing insomnia, comprising jujuboside A, ginsenoside Rb1, and gypenosides XLIX as active ingredients, and a pharmaceutically acceptable carrier; wherein, The weight ratio of jujube seed saponin A to gypenosides XLIX is 1:3-5; and, The weight ratio of ginsenoside Rb1 to gypenosides XLIX is 1:3 to 5.

2. The saponin composition according to claim 1, wherein, The jujube seed saponin A and gypenosides XLIX are the only active ingredients that can upregulate the level of γ-aminobutyric acid in brain tissue; and / or the ginsenoside Rb1 and gypenosides XLIX are the only active ingredients that can upregulate the level of 5-hydroxytryptamine in brain tissue.

3. The use of a saponin composition comprising jujube seed saponin A, ginsenoside Rb1, and gypenosides XLIX in the preparation of a medicament for treating and / or preventing insomnia; wherein, In the saponin composition The weight ratio of jujube seed saponin A to gypenosides XLIX is 1:3-5; and, The weight ratio of ginsenoside Rb1 to gypenosides XLIX is 1:3 to 5.

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