WO2013174245A1 - Hederagenin derivative and preparation method and uses thereof - Google Patents

Description

Technical field

 The invention belongs to the technical field of medicine, and particularly relates to an ivy saponin derivative, a preparation method and application thereof.

Background technique

 Ivy saponin is a common aglycone in Chinese medicinal materials, mainly found in continuation, pre-existing, wood, honeysuckle and so on. Ivy saponin is a white powder with low polarity, slightly soluble in methanol and ethanol, and hardly soluble in water. It has been reported that Ivy saponin has the function of protein tyrosine phosphatase PTP1B inhibitor, which can form anti-diabetic drugs and health care products, and can provide for prevention, diagnosis, detection, protection, treatment and research of depression and its directly related diseases. A new source of medicine.

 However, since the ivy saponin is hardly soluble in water, the solubility in ethanol is not high. The research data show that the bioavailability of the product is also low, and the daily dosage is large. The present invention changes or enhances the biological activity by changing the structure.

 Chinese patent CN200810032325.2 discloses the use of an ivy saponin and a derivative thereof for preparing an antidepressant product, but the ivy saponin derivative thereof refers to an ivy saponin salt derivative (referred to as sodium) Salt or potassium salt) is prepared by dissolving ivy saponin in an ethanol solution, reacting with a corresponding alkali solution, and obtaining a salt upon recrystallization. The role in antidepressant was demonstrated by an in vitro activity test.

 At present, derivatives obtained by semi-synthesis of ivy saponin are not reported at present, and the salts of the derivatives thereof have not been reported yet. It is very important to improve the pharmacological properties, improve the biological activity, improve the absorption and metabolism, and improve the drug efficacy by preparing new derivatives of ivy saponins, changing physical and chemical properties and active centers.

Summary of the invention

 A primary object of the present invention is to provide an ivy saponin derivative.

 Another object of the present invention is to provide a process for the preparation of an ivy saponin derivative.

 The invention is achieved by the following technical solutions:

An Ivy saponin derivative having the following formula:

 among them:

Ri and R _{2 are the} same or different and are independently represented as -OR', R' is -COCH ₃ , -CO(CH ₂ ) _n CH ₃ , -S0 ₃ H, -CO(CH ₂ ) _n COOH, -ortho Sulfonic acid benzoyl, - sulfonic acid benzoyl, - p-sulfonic acid benzoyl, - p-toluenesulfonyl, - o-carboxybenzoyl, - meta-carboxybenzoyl, - p-carboxybenzoyl, - Maleic acid, -fumaryl, -methanesulfonyl or H, provided that the two are not simultaneously H, wherein _n = l-3 _;

Is 11, Na, K or NH ₃ ;

When R' in R ₂ contains a carboxyl group, the carboxyl group may further react with a base to form one or more salts.

Preferably, R' is -COCH ₃ or -CO(CH ₂ ) ₂ COOH.

 The preparation method of the ivy saponin derivative of the invention is obtained by using an ivy saponin as a raw material by an acylation reaction, an esterification reaction or a transesterification reaction, and the specific method is as follows:

Acylation reaction:

 Weigh the appropriate amount of ivy saponin, add 20~50 times the amount of solvent, 0.05~15 times the amount of catalyst, add the toluene solution containing the acid halide under stirring, react 50-7CTC for 5-10 hours, add water for 1-3 hours, The aqueous layer was separated, and the solvent was evaporated under reduced pressure. 10-25 times of 95% ethanol was added, stirred and dissolved, decolorized with activated carbon, filtered while hot, and the ethanol was recovered under reduced pressure, and washed with water to obtain an ivy saponin derivative.

Esterification reaction:

 Weigh the appropriate amount of acid anhydride or carboxylic acid, add 20~50 times solvent, 0.05~15 times the amount of catalyst, stir and heat, add 0.1~1 times the amount of ivy saponin, reflux reaction for 5~10h, distill off the solvent under reduced pressure, add 10-25 times the amount of 95% ethanol, stirred and dissolved, decolorized with activated carbon, filtered while hot, and the ethanol was recovered under reduced pressure, and washed with water to obtain an ivy saponin derivative.

Transesterification reaction:

Weigh the appropriate amount of carboxylic acid ester, add 0.1~1 times the amount of ivy saponin, add 20~50 times the amount of solvent, 0.05 15 Double the amount of catalyst, stir and heat, reflux reaction for 5~10h, add 10% sodium carbonate solution, remove the water layer, remove the solvent in the organic layer under reduced pressure, add 10-25 times of 95% ethanol, stir to dissolve, decolorize with activated carbon The mixture is filtered while hot, the ethanol is recovered under reduced pressure, and washed with water to obtain an ivy saponin derivative.

 The solvent in the above preparation method is pyridine or toluene; the catalyst is pyridine or triethylamine in the acylation reaction, and concentrated sulfuric acid or p-toluenesulfonic acid in the esterification or transesterification reaction.

 The ivy saponin of the present invention can be extracted from a Chinese medicinal material by a known preparation method or directly obtained from the market.

 In the present invention, an ivy saponin derivative is obtained by using an ivy saponin as a raw material by an acylation reaction, an esterification reaction or a transesterification reaction, and the derivative can be further reacted with a base to obtain a salt thereof. The method has the advantages of high yield and purity of ivy saponin derivatives semi-synthesized from ivy saponins, which can reach more than 95%, simple preparation process, high conversion rate of raw materials, suitable for industrial production, and easy to popularize and apply.

 The salt of the ivy saponin derivative of the present invention may be a single salt, a double salt or a poly salt. It can be prepared by dissolving the ivy saponin derivative in 95% ethanol, adding 1-10% alkali solution at -10 to 30 ° C to adjust the pH to 9-11, and cooling the precipitated solid to obtain the ivy saponin. a salt of a meta-derivative. The salt of the ivy saponin derivative may be an ivy saponin derivative sodium salt, an ivy saponin derivative potassium salt or an ivy saponin derivative ammonium salt. Preferably, the salt of the ivy saponin derivative is a sodium salt of an ivy saponin derivative or a potassium salt of an ivy saponin derivative.

 The present invention also provides the use of an Ivy saponin derivative or a salt thereof for the preparation of an antidepressant. The pharmaceutically acceptable carrier is prepared by adding a pharmaceutically acceptable carrier to a pharmaceutically acceptable carrier by using a saponin derivative or a salt thereof as a main active ingredient, and adding a pharmaceutically acceptable carrier; Crystalline cellulose, hydroxypropylmethylcellulose, gelatin, starch, dextrin, magnesium stearate, lactose, glucose, talc, sodium chloride, phosphate buffered saline, glycerol, ethanol, etc.; the dosage form may be a tablet Agents, capsules, granules, oral liquids, injections, and the like. The dose of the medicament of the present invention may vary depending on the route of administration, the age and weight of the patient, the type and severity of the disease to be treated, and the daily dose may be preferably from 100 to 600 mg.

 The present invention further verifies the pharmacological activity of the ivy saponin derivative or a salt thereof, and the experiment shows that the activity of the ivy saponin derivative or its salt is higher than that of the aglycon and aglycone, and the pharmacological activity thereof has It is obviously improved, has obvious therapeutic effects on depression, has obvious pharmacological effects, and is stable in nature, and can be used for preparing antidepressant drugs.

detailed description The invention is further illustrated by the following specific embodiments. The following examples are specific embodiments of the present invention, but the embodiments of the present invention are not limited by the following examples, and any other embodiments without departing from the spirit and principle of the invention The changes, modifications, substitutions, combinations, and simplifications that are made below are equivalent substitutions and are included in the scope of the present invention.

Example 1 Preparation of Ivy Saponin-3,23-Disuccinate

Weigh 28 g of succinic anhydride into a three-necked flask, add 1000 ml of toluene, 300 ml of triethylamine, and heat with stirring. When the temperature is close to reflux, add 22 g of ivy saponin, reflux for 8 hours, and distill off the solvent under reduced pressure. Adding 450 ml of 95% ethanol, stirring and dissolving, decolorizing with activated carbon, filtering while hot, recovering ethanol under reduced pressure, and washing with water to obtain 31 g of ivy saponin-3,23-disuccinate.

Example 2 Preparation of Ivy Saponin-3,23-Disuccinate

Weigh 22 grams of ivy saponin into a three-necked flask, add 600 ml of pyridine, add 40 g of succinic acid in toluene solution with stirring, react at 60 ° C for 8 hours, add water for 2 hours, separate the water layer, reduce The solvent was distilled off, and 450 ml of 95% ethanol was added thereto, and the mixture was stirred and dissolved, decolorized with activated carbon, filtered while hot, and the ethanol was recovered under reduced pressure, and washed with water to obtain 32 g of ivy saponin-3,23-disuccinate.

Example 3 Preparation of Ivy Saponin-3,23-Disuccinate

Weigh 34 grams of succinic acid and 22 grams of ivy saponin into a three-necked flask, add 1000 ml of toluene, 12 ml of concentrated sulfuric acid, stir and heat. When the temperature is close to reflux, add, reflux for 8 hours, and distill off the solvent under reduced pressure. Adding 450 ml of 95% ethanol, stirring and dissolving, decolorizing with activated carbon, filtering while hot, recovering ethanol under reduced pressure, and washing with water to obtain 32 g of ivy saponin-3,23-disuccinate.

Example 4 Preparation of Ivy Saponin-3,23-Disuccinate

Weigh 40 g of dimethyl succinate, 22 g of ivy saponin, 2 g of p-toluenesulfonic acid into a three-necked flask, add 1000 ml of toluene, stir and heat, reflux for 12 hours, add 10% sodium carbonate solution 200 ml. After reacting for 30 minutes, the aqueous layer was separated, and the organic layer was evaporated to dryness under reduced pressure. <RTI ID=0.0>&&&&&&&&&&&&&&&&&&& 25-bis succinate 25 g. Example 5 Preparation of Ivy Saponin-3, 23-Acetate

Weigh 25 grams of acetic acid into a three-necked flask, add 1000 ml of toluene, 300 ml of triethylamine, add 22 g of ivy saponin, stir and heat, reflux for 5 hours, distill off the solvent under reduced pressure, add 95% ethanol 450 ML, stirred and dissolved, decolorized with activated carbon, filtered while hot, ethanol was recovered under reduced pressure, and washed with water to obtain 28 g of ivy saponin-3, 23-acetate. Example 6 Preparation of Usan Saponin-3, 23-Acetate

Weigh 3⁄4 of acetic acid 1 | 18 g, 22 g of ivy saponin into a three-necked flask, add 1000 ml of toluene, p-toluene. Heat under stirring, reflux for 12 hours, distill off the solvent under reduced pressure, add 450 ml of 95% ethanol. The mixture was stirred and dissolved, decolorized with activated carbon, filtered while hot, and the ethanol was recovered under reduced pressure, and washed with water to obtain 21 g of Ivy saponin-3, 23-acetate.

Example 7 Preparation of Ivy Saponin - Disodium Salt of 3,23-Disuccinate

Ivy saponin-3,23-disuccinate was prepared according to Example 1, and 10 g of ivy saponin-3,23-disuccinate was weighed and dissolved in 100 ml of absolute ethanol, and added at about 10 °C. Adjust the pH to about 11 with 3% sodium hydroxide solution, cool the precipitated solid, filter it, wash it with absolute ethanol, and dry it to get the disodium of ivy saponin-3,23-disuccinate.

Structure confirmation of saponin/[>3,23-diperate disodium salt

 The chemical structure is as follows:

ESI-MS (m/z): 738 [M ⁺ +Na] ⁺ ;

NMR NMR (400MH _Z , CDC1 ₃ ) δ: 0.99 ( s,6H ) , 1.04 (s,9H) , 1.30 (s,3H) , 1.38—1.61 (m,16H,CH ₂ ,CH), 1.80 (q, J=7.1 , 2H), 2.01—2.04 (m,4H,CH ₂ ), 2.43 (t,J=6.0 H), 2.53 (U:7.1 2H), 2.73 (t,J=7.1 2H), 2.83 (t , J=7.1 4H), 3.89 (t, J=7.0 H), 4.13 (s, 2H), 5.29 (t, J=6.2 H);

¹ C NMR (100MHz, CDCl ₃ ) δ: 33.8 (C-1), 24.1 (C-2), 75.3 (C-3), 40.7 (C-4), 53.4 (C-5), 1 8.3 (C -6). 33. KC-7), 39.9(C-8). 47.7(C-9), 37.6(C-10), 23.8(C-11), 122.4(C-12), ! 43.7(C - 13 ). 41 .4(C-14). 29.1 (C- 1 5). 46.6(C-17), 41.4(C-18), 46.6(C-19),

5

Replacement page (Article 26) 30.7(C-20), 34.2(C-21), 32.5(C-22), 66.0(C-23), 21.9(C-24), 15.9(C-25), 17.1(C-26), 25.9 (C-27), 184.4 (C-28), 26.9 (C-29, C-30), 171.8 (C-31, C-35), 31.0 (C-32, C-36), 34.4 (C- 33, C-37), 178.0 (C-34, C-38).

Example 8

According to the dosage of 1000 preparation units, 60 g of ivy saponin-3, 23-disuccinate, 80 g of microcrystalline cellulose, 40 g of starch, 15 g of sodium carboxymethyl starch, 5 g of microsilica gel, and 1000 capsules were prepared. Capsules, Specifications: Each tablet contains 60mg of the main drug, the theoretical weight of 200mg.

The above-mentioned raw and auxiliary materials are first passed through a 80 mesh sieve, and the ivy saponin derivative, microcrystalline cellulose starch, sodium carboxymethyl starch is uniformly mixed according to the prescription amount, and the mixture is uniformly mixed, and the soft material is made of 80% medicinal ethanol, and 24 mesh is used. The granules were sieved, dried at 60 ° C for 1 hour, sieved through 20 mesh, and added to the micro-silica gel, and filled into capsules to obtain 950 capsules of ivy saponin-3,23-disuccinate capsule.

Example 9

According to the dosage of 1000 preparation units, 180 g of ivy saponin-3,23-disuccinate, 120 g of hydroxypropylmethylcellulose, 50 g of microcrystalline cellulose, 6000 g of polyethylene glycol, 4 g of magnesium stearate , a total of 1000 tablets, specifications: Each tablet contains 300mg of the main drug, the theoretical weight of 360mg.

The above-mentioned raw and auxiliary materials are respectively passed through a 100-mesh sieve, and the main drug, hydroxypropylmethylcellulose, microcrystalline cellulose, and polyethylene glycol are weighed according to the prescription amount, and uniformly mixed, and the soft material is made of 95% medicinal ethanol. The mesh was granulated, dried at 60 ° C for 4 hours, sieved through 20 mesh, and added with magnesium stearate and compressed to obtain 912 tablets of ivy saponin-3,23-disuccinate sustained-release tablet. Example 10 Therapeutic effect of Ivy saponin derivatives on two depression model mice

1. Test materials

1.1 Experimental animals

Kunming mice (6 weeks old, weighing 20 ± 2g), male, provided by Guangdong Medical Laboratory Animal Center (license number: SCXK (Guangdong) 2003-2002, Guangdong Supervisory Certificate 2008A006). Animal feeding conditions: temperature (23 ° C ± 2 ° C). After the purchase, the experiment was carried out after 3 days of adaptive feeding.

1.2 Drugs and reagents

Test drug: Ivy saponin derivative (HEDS), produced by Guangzhou Boji Pharmaceutical Biotechnology Co., Ltd., batch number: 20100413; Ivy saponin (HED), produced by Guangzhou Boji Pharmaceutical Biotechnology Co., Ltd. Provided, batch number: 20101031; Ivy saponin sodium (HEDN), produced by Guangzhou Boji Pharmaceutical Biotechnology Co., Ltd., batch number: 20100901. Western medicine reference drug: amitriptyline hydrochloride (Source: Changzhou Si Yao Pharmaceutical Co., Ltd., Specification: 25mg/tablet, batch number:

201004083).

Traditional Chinese medicine reference drug: Shugan Jieyu Capsule (Source: Chengdu Kanghong Pharmaceutical Group Co., Ltd.; Batch No.: 100602; Specification: 0.36g/grain)

Modeling drugs: Reserpine injection (Source: Guangdong Bangmin Pharmaceutical Factory Co., Ltd., specifications lmg * lml-l, batch number 090717

1.3 Experimental instruments

Electronic thermometer (batch number: 00196505 manufacturer: Beijing Infant Technology Development Center); multi-functional mouse autonomic instrument, mouse swimming device (homemade); stopwatch, balance, gavage needle, opaque water tank.

Reserpine mouse model

2.1 Experimental grouping and administration

The mice were randomly divided into 8 groups according to body weight, and 10 rats in each group were administered according to the following methods. The administration volume was 0.2 ml/10 g. After the last administration for 1 h, each mouse was intraperitoneally injected with reserpine 2.5 mg. /kg.

Normal group: Normal feeding, no medication.

Model group: Distilled water was given by gavage once a day for 7 days.

Western medicine control group: Pre-formed amitriptyline hydrochloride solution was administered by gavage, and administered at a dose of 10 mg/kg once a day for 7 days.

Chinese patent medicine control group: A pre-formulated Chinese medicine solution was administered by gavage, and was administered at a dose of 296 mg/kg once a day for 7 days.

 HEDS high-dose group: HEDS solution was administered by gavage at a dose of 60 mg/kg once daily for 7 days. Low dose group of HEDS: HEDS solution was administered by gavage at a dose of 30 mg/kg once daily for 7 days. HEDN group: HEDN solution was administered by gavage at a dose of 60 mg/kg once daily for 7 days.

HED group: HED solution was administered by gavage at a dose of 60 mg/kg once daily for 7 days.

2.2 Indicator determination and detection methods

 2.2.1 Detection of rectal temperature After intraperitoneal injection of reserpine and immediately after 4 hours, the electronic thermometer probe was inserted into the anus of the mouse, and the depth was measured by the thermometer probe completely entering the anus, maintained for at least 10 s, and the anus temperature of each group was recorded. The differences in anal temperature changes between the drug-administered group and the control group are shown in Table 1.

2.2.2 Inability to observe the intraperitoneal injection of reserpine for 1 h, the mice were placed in a circle of 7.5 cm in diameter for 15 s, and the circle-out rate of each group of mice was calculated. The results are shown in Table 1. 2.2.3 Observation of drooping eyelids After intraperitoneal injection of reserpine for 1 h, the number of animals with more than half of the eyelids closed in each group was observed. The results are shown in Table 1.

 2.2.4 The decrease of anal temperature in mice was expressed as mean ± standard deviation (± s)). The measurement data were analyzed by one-way analysis of variance for completely randomized design. Statistical software SPSS13.0 was used for statistical analysis. P < 0.05 was considered statistically significant.

 2.3 Results

 It can be seen from Table 1 that the difference in the anal temperature of the mice in each administration group was statistically different from that in the model group, and the difference between the western medicine control group and the high dose HEDS group was very significant.

 Table 1 Observation of mouse indicators in each group ( ± s, n=10)

 Note: Compared with the model group, * Ρ < 0.05, ** Ρ < 0.01.

 3, forced swimming stress depression model

 3.1 Experimental grouping and administration

 The mice were randomly divided into 8 groups according to body weight, and 10 rats in each group were administered according to the following methods, and the administration volume was 0.4 ml/10 g. Normal group: Normal feeding, no medication was given.

 Model group: Distilled water was given by gavage once a day for 14 days.

 Western medicine control group: Pre-formed amitriptyline hydrochloride solution was administered by gavage, administered at a dose of 10 mg/kg once a day for 14 days.

 Chinese patent medicine control group: The pre-formulated Chinese medicine solution was administered by gavage, and was administered at a dose of 296 mg/kg once a day for 14 days.

 HEDS high-dose group: HEDS solution was administered by gavage at a dose of 60 mg/kg once daily for 14 days.

 Low dose group of HEDS: HEDS solution was administered by gavage at a dose of 30 mg/kg once daily for 14 days.

HEDN group: HEDN solution was administered by gavage at a dose of 60 mg/kg once daily for 14 days. Hi-D fR: HED solution was administered by gavage at a dose of 60 mg/kg once daily for 14 days.

3.2 Indicator determination and detection methods

3.2.1 Θ Activity test Each group was placed on the autonomous activity meter after the last administration for 1 hour, and the spontaneous activity of the mice within 10 minutes was measured immediately. The results are shown in Table 2 _;

 3.2.2 Small forced swimming In addition to the normal group, each group was placed in an opaque glass jar with a height of 20 cm, h Vv. 10 cm, water depth of 10 cm and water temperature of about 20 ° C after the last administration for 1 h. : 00-10: 00 time period strong side swimming 5mm, forced swimming for 14d. The normal group of mice were not treated except for the necessary squirrel cage cleaning. On the ld, 7d, and 14d, the swimming time of each group was observed (the mice were swimming for 6 min, and the immobility time was 4 min after the accumulation). The test results are shown in Table 3.

3.3 Data Statistics and Processing

The data of each group were expressed by the mean soil standard deviation (soil s). The measurement data were analyzed by one-way ANOVA with completely random design. Statistical software SPSS13.0 was used for statistical analysis. P < 0.05 was considered statistically significant.

 3.4 Experimental results

As shown in Shan 2 and Table 3, there was no statistically significant difference between the statistical indicators of each group and the normal group.

 Small Π Π Activity (soil s, η=10)

 Res.T Mov.S Mov.F. Total distance

 Group average speed

 (s). (s). (s) (mm) Normal group 432.00 士 67.24 133.22±42.50 34.68±26.26 12957.15±4720.42 21.60±7.87 Model group 392.30±48.61 160.54±30.87 47.14±20.57 15700.4±3499.26 26.17±5.83

 429.08±71.47 135.28±49.52 35.58±22.76 13385.54±5039.27 22.31±8.40 Chinese medicine group 441.74±64.62 122.36±44.78 35.86±21.04 12612.81±4222.15 21.02±7.04

HEDS high 453.42 soil 44.53 116.80±32.19 29.72±13.61 11709.89±3112.78 19.52±5.19

IIHDS low 438.32±47.37 126.6 ± 35.98 35±13.46 12765.97±2936.36 21.28±4.90 iii:i) ι 439.5士 62.77 122.90±42.75 37.56±23.80 12917.77±4314.98 21.53±7.19

\\i ^: .D 'ί\\. 446.64士57.32 123.56±48.87 36.56±22.33 12637.81±4253.27 21.48±8.02 Note: Compared with the normal group, there was no statistically significant difference between the groups, suggesting that HEDS has no excitatory effect on the central nervous system. .

Table 3 Forced swimming mice immobility time (S ± s, n = 10) units (seconds)

9

Replacement page (Article 26) Group IS: Swimming time

 ^, Day 1 Day 7 Day 14 End Group 150.3±37.42 143.7±38.21* 113.5±2.69*

 Group] 24.7 soil 27.24 178.7±26.24 173.3 ±23.85

 Medium 131.8±25.25 169.6±30.63 144.4±41.73

 123.9±29.14 154.4±37.95 135.6±28.68*

 I38.4±22.20 160.4±21.61 135.3±35.67*

 .os! : Lf'jiii ll. Π4.8±35.69 154.5 ±32.26 138.7±25,43*

 HEDN group 134.4 soil 32.79 158.4±37.67 141.4±34.42*

 HED group 128.3±26.55 161.3±32.45 148.6±46.75

Note: Compared with the model group, *P<0.05c

Analysis of results:

 Reserpine is a vesicle reuptake inhibitor that leaves the transmitter outside the vesicle and is easily degraded by monoamine oxidase, thereby depleting catecholamines (norepinephrine, adrenaline, dopamine, and 5-HT), causing behavior And physiological changes. In this experiment, high and low doses of HEDS significantly reduced the degree of ptosis in the model mice, suggesting that t]1] may be associated with agonistic alpha-adrenergic effects. Both high and low doses of HEDS can reduce the body drop of reserpine, suggesting that the drug can also act through stimulating β-adrenergic dysmenorrhea.

 The absolute swimming experiment is based on the pathogenesis theory of environmental factors, using the classic mouse depression model established by desperate behavior, for the preliminary evaluation of the efficacy of antidepressants. Our experimental results show that high and low dose HEDS can significantly reduce the duration of desperate motion in mice forced swimming, suggesting that HEDS has a better therapeutic effect.

 Treatment of two mouse depression models showed that HEDS showed a stronger antidepressant effect than HEDN and HED at the same dose, especially with respect to HED.

10

 Replacement page (Article 26)

Claims

 Claim 1. An Ivy saponin derivative having the following formula:

among them: Ri and R _{2 are the} same or different, and are independently represented as -OR', and R' is -COCH ₃ , -CO(CH ₂ ) _n CH ₃ , -S0 ₃ H, -CO(CH ₂ ) _n COOH, - o-sulfonic acid benzoyl, - m-sulfonic acid benzoyl, - p-sulfonic acid benzoyl, - p-toluenesulfonyl, - o-carboxybenzoyl, - m-carboxybenzene Formyl, -p-carboxybenzoyl, -maleyl, -fumaryl, -methanesulfonyl or H, provided that the two are not simultaneously H, wherein _n = l-3 _; Is 11, Na, K or NH ₃ . The ivy saponin derivative according to claim 1, wherein the R' is -COCH ₃ or -CO(CH ₂ ) ₂ COOH.  The method for preparing an ivy saponin derivative according to claim 1, which is characterized in that the saponin element is The raw material is obtained by an acylation reaction, an esterification reaction or a transesterification reaction, and the specific method is: weighing an appropriate amount of acid halide, acid anhydride, carboxylic acid or carboxylate, adding 20 to 50 times of solvent, 0.05 to 15 times of catalyst, Stir and heat, add 0.1~1 times the amount of Ivy saponin, reflux reaction for 5~10h, distill off the solvent under reduced pressure, add 10-25 times the amount of 95% ethanol, stir to dissolve, decolorize with activated carbon, filter by hot, recover by vacuum Ethanol, washed with water to obtain an ivy saponin derivative.  The method for producing an ivy saponin derivative according to claim 3, wherein the solvent is pyridine or toluene. The method for producing an ivy saponin derivative according to claim 3, wherein The catalyst is pyridine, triethylamine, concentrated sulfuric acid or p-toluenesulfonic acid.  6. Use of an ivy saponin derivative or a salt thereof for the preparation of an antidepressant.  The use of the ivy saponin derivative or a salt thereof according to claim 6, wherein the salt of the ivy saponin derivative is a single salt, a double salt or a multi-salt .  The use of an ivy saponin derivative or a salt thereof according to claim 6, wherein the salt of the ivy saponin derivative is a sodium salt of an ivy saponin derivative An ivy saponin derivative potassium salt or an ivy saponin derivative ammonium salt.  The use of the Ivy saponin derivative or a salt thereof according to claim 8, in the preparation of an antidepressant, wherein the salt of the ivy saponin derivative is a sodium salt of an ivy saponin derivative Or the potassium salt of the ivy saponin derivative.