RU2419447C2 - Medicinal mixture, possessing hepatoprotective and anti-inflammatory activity - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine. Mixture consists of medicinal plants: inflorescences of pot marigold, peppermint leaves, Baikal skullcap root, black leaves and root of badan, shoots of shrubby cinquefoil, with the following component ratio, wt fr.: inflorescences of pot marigold 3; peppermint leaves 1; Baikal skullcap root 2; rhizome and black leaves of badan - 1+1; shoots of shrubby cinquefoil 2. Clinical treatment with claimed mixture has resulted in positive effect in case of alcoholic hepatitis in 150 patients.

EFFECT: creation of mixture for treatment and prevention of alcoholic hepatitis.

10 tbl

Description

The invention relates to medicine and relates to the creation of a collection with hepatoprotective and anti-inflammatory activities.

It is known that in the environment, consumed products there is a huge amount of hepatotoxic xenobiotics with which a person has been in contact throughout his life. In recent decades, the proportion of diseases of the gastroenterological pathology has increased and has a further tendency to spread, about half of which are liver diseases. Hepatoprotective agents for the pathogenetic therapy of acute and chronic diseases of the hepatobiliary system normalize the structure, metabolism, and function of the liver parenchyma.

It is known that chronic alcohol consumption is accompanied by damage to the liver (fatty infiltration, hepatitis), the small intestine (impaired peristalsis). The main biological effect of ethanol is associated with impaired tissue and cellular metabolism, suppression of the immune system, toxicity [Collier J.A. B., Lontmore J. M., Harvey J. G. Oxford Guide for Clinicians. M .: Medicine, 2000]. Chronic alcoholism is often accompanied by alcohol enteritis, the main manifestation of which is diarrhea [Shabanov PD Guide to addiction. St. Petersburg: Publishing House "Lan", 1999.- 352 p.]. The use of synthetic drugs (antibiotics, NSAIDs) does not always provide the desired effect, in some cases exacerbates the course of the disease. In this regard, the development and use of herbal medicines that are quite pronounced effectiveness and safety in the treatment and prevention of alcoholic damage to the liver and intestines seems to be relevant. The therapeutic effect is achieved due to a wide range of pharmacotherapeutic properties of medicinal plants: hepatoprotective, choleretic, anti-inflammatory, antimicrobial, astringent, immunomodulating, etc.

The proposed drug collection (conventional name "Calendula-6") has a pronounced hepatoprotective and anti-inflammatory activity, consists of the following medicinal plants, parts by weight:

Inflorescences of calendula officinalis 3.0 Peppermint leaves 1,0 The roots of Scutellaria baicalensis 2.0 Rhizomes of Badan 1,0 Leaves black frankincense 1,0 Shrubs 2.0

To prepare 1000 g of the proposed collection, take the inflorescences of calendula officinalis 306 g; peppermint leaves 102 g; the roots of Scutellaria baicalensis 204 g, rhizomes of frankincense 102 g., leaves of black incense thick-leaved 102 g, shoots of five-leaved shrub 204 g, mixed, crushed in a mill to a particle size of 1.0-2.0 mm, sieved through sieve No. 2 and weighed. Loss of raw materials during grinding is 2%.

The composition of the collection is made taking into account the contribution of individual plants to the hepatoprotective and anti-inflammatory effects of the collection. Biologically active substances (BAS) of each component make a certain contribution to the normalization of the function of the hepatobiliary system in alcoholic liver damage. Hepatoprotective and anti-inflammatory activities are shown by BAS (carotenoids, flavonoids, polysaccharides, triterpene glycosides, essential oils, amino acids, etc.) of calendula, peppermint, Scutellaria baicalensis [S.Ya. Sokolov, I.P. Zamotaev. Handbook of Medicinal Plants (Herbal Medicine). - M.: Medicine. 1990.428 s .; O.A. Konovalova, K.K. Rybalko. Biologically active substances of Calendula officinalis L. // grows. resources. 1990.V. 26. issue 3. S.448-463; E.D. Goldberg, A.M. Digay, V.I. Litvinenko, and others. Baikal skullcap. Phytochemistry and pharmacological properties. Tomsk 1994.222 s .; I.G. Nikolayev, V. B. Khobrakova, M. M. Aryaeva. Five-leaved shrub. Medicinal plants of Tibetan medicine. Series. - Ulan-Ude: Publishing House of the BSC SB RAS. - 2000.120 s.]. Anti-inflammatory, astringent, and antimicrobial properties are the main pharmacological properties of the preparations of the roots of incense containing phenolic compounds [Plant resources of the USSR: Flowering plants, their chemical composition, use; Hydrangeaceae-Haloragaceae families. - L .: Nauka, 1987. - S.8-10]. The extract of black leaves of badan shows adaptogenic, antistress, immunomodulatory, anti-inflammatory, antitoxic activity [P.B.Lubsandorzhieva. Badan is thick-leaved. Medicinal plants of Tibetan medicine. Series. - Ulan-Ude: Publishing House of the BSC SB RAS. - 2003. - 90 p.].

To prove the validity of the proposed composition of the collection, the authors conducted a series of experiments, the data of which confirm its pronounced effectiveness in alcoholic liver damage in experimental animals. The use of the Calendula-6 collection under clinical conditions has shown its beneficial effect on the functional state of the liver in patients with chronic alcoholism.

The samples of the collection made from medicinal raw materials, the quality of which corresponds to the current articles of the Global Fund, XI ed. Quantitative determination of biologically active substances in the collection and broth (1:10) was carried out according to the methods of the Global Fund XI ed. [State Pharmacopoeia of the USSR: issue 1. General methods of analysis. Ministry of Health of the USSR. - 11th ed., Ext. - M.: Medicine. - 1987. - 337 p .; issue 2. General methods of analysis. Medicinal plant material. Ministry of Health of the USSR. - 11th ed., Ext. - M.: Medicine. - 1990. - 400 p.]. The analysis data to determine the quantitative content of biologically active substances in "Calendula-6" are shown in table 1.

Table 1
The quantitative content of biologically active substances in the collection "Calendula - 6" Name The content of biologically active substances Assembled "Calendula-6",% In the broth of the collection (1:10), mg / ml Flavonoids, in terms of luteolin 2.76 ± 0.01 0.91 ± 0.02 Tannins, in terms of tannin 7.53 ± 0.08 3.16 ± 0.75 Polysaccharides 4.99 ± 0.35 1.5 ± 0.02 Ascorbic acid 1.88 ± 0.06 0.22 ± 0.01

An example of a specific implementation.

Shredded and sifted through a sieve with a diameter of 0.5 mm inflorescences of calendula officinalis 3.0 g; peppermint leaves 1.0 g; Scutellaria baicalensis roots 2.0 g; rhizomes of frankincense 1.0 g; leaves black berry frangipani 1.0 g; shrubs of a five-leaved shrub 2.0 g are mixed, placed in a flask with a capacity of 300 ml, 100 ml of distilled water are added, the flask is combined with a reflux condenser and heated in a water bath, maintaining boiling for 30 minutes. After cooling for 10 min, the extraction is filtered through a paper filter, the obtained filtrate is used to determine pharmacological properties.

The study of hepatoprotective activity "Calendula-6." The studies were conducted on 375 outbred white rats of both sexes with an initial weight of 150-170 g. Statistical processing of the data was carried out using the Mann-Whitney U-test [Sergienko VI, Bondareva IB Mathematical statistics in clinical studies. - M., 2000.263 s.]. Alcoholic hepatitis in animals was caused by intragastric administration of a 40% aqueous solution of ethyl alcohol in a volume of 7 ml / kg of animal weight once a day for 21 days [I. Mansurova. Olimova S.O. The activity of microsomal ethanol-oxidizing system in alcohol intoxication // Experimental hepatology. Riga: Znatne, 1985. P.41]. The studied collection "Calendula-6" was introduced in the form of a decoction in an experimental therapeutic dose into the stomach of white rats in a volume of 1 ml / 100 g of animal weight 1 time per day for 21 days. The interval between the introduction of the broth "Calendula-6" and ethanol corresponded to 5-6 hours. To another group of white rats, a comparison drug was administered according to a similar scheme - a decoction of the collection intended for the treatment of hepatitis and chronic colitis (the conditional name for the collection of FHCC) and consisting of chamomile flowers 2 hours, calendula flowers - 2 hours, peppermint leaves 2 hours, herbs of violet tricolor 1 hour [Krylov A.I., Marchenko V.A. Guide to herbal medicine. St. Petersburg: Publishing House Peter, 2000. 416 p.]. Animals of the control group received distilled water in an appropriate volume.

The functional state of the liver of animals was evaluated in the dynamics of the development of damage on days 7, 14 and 21 from the beginning of the experiment. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (ACT), alkaline phosphatase (ALP), cholesterol, β-lipoproteins, and bilirubin thymol samples in blood serum were determined according to generally accepted methods [Laboratory research methods in the clinic: Reference book / V. Menshikov, Delektorskaya L.N., Zolotnitskaya R.P. et al .: Ed. V.V. Menshikov. - M., 1987. - 368 p.]. The intensity of lipid peroxidation (LP) was evaluated by the content of malondialdehyde (MDA) in blood serum [Temirbulatov R.A. Seleznev E.I. A method of increasing the intensity of free radical oxidation of lipid-containing blood components and its diagnostic value // Laboratory. - 1981. - No. 4. - p.209-211] and in the homogenate of the liver [Steel I.D., Garishvili T.G. Method for determination of malondialdehyde using thiobarbituric acid // Modern Methods in Biochemistry.- M., Medicine, 1977.- p.66-68]. Serum catalase activity was determined by the method of G. A. Bobenko, M. N. Gaynatsky [Bobenko G. A., Gaynatsky M. N. Determination of catalase activity in red blood cells and serum. // Laboratory, 1976, No. 3]. The analysis data are shown in table 2.

Administration of ethyl alcohol per os to white rats causes an acceleration of lipid peroxidation processes in membranes on the 7th day of observation: the MDA content in the liver homogenate of white rats in the control increases by 43% and remains at a high level during all subsequent monitoring periods (Table 2). With the intensification of LPO processes, manifestations of the cytolysis syndrome are associated. So, on the 7th day of the experiment, against the background of the introduction of ethanol in the blood serum, the activity of membrane-bound enzymes (AcT and Alt) increases by 4.2 and 4.6 times compared with indicators in the intact group of animals. Along with this, the activity of alkaline phosphatase in the blood increases by 1.6 times, cholesterol by 22%, which indicates the development of cholestasis, which is due to impaired secretion and outflow of bile. The development of cytolysis, cholestasis and increased LPO processes are associated with a decrease in the rate of bile secretion, inhibition of synthesis and excretion of bilirubin, cholesterol and bile acids with bile. Thus, in animals treated with ethanol, the rate of bile secretion decreases by 7% for 7 days, the content of bile acids, bilirubin and cholesterol, respectively, by 36%, 33% and 22% compared with the control (table 3).

The course introduction of "Calendula-6" in an experimental therapeutic dose significantly reduced the toxic effect of ethanol. On the 7th day of the experiment, inhibition of LPO processes is observed: the MDA content in the liver homogenate of animals treated with Calendula-6 is significantly lower than in animals in the control. Along with this, a decrease in the levels of ALT, AcT activity is noted. The most pronounced pharmacotherapeutic effect of "Calendula-6" in the used dose has on the manifestations of cholestatic syndrome and the phenomena of dysproteinemia. In addition, a decrease in the content of cholesterol, alkaline phosphatase, and bilirubin was noted by 36%, 24%, and 26%, respectively, compared with the corresponding indices in the control (Table 2). In the subsequent follow-up periods (14-21 days), changes in biochemical parameters in the experiment indicate a favorable dynamics of the involution of signs of cholestasis in animals treated with Calendula-6 than when using the comparison drug FHC for ethanol hepatitis.

Thus, Calendula-6 in an experimental therapeutic dose has a beneficial effect on the functional state of the liver of animals in the early stages of development of ethanol hepatitis.

2. The study of anti-inflammatory activity "Calendula-6." The experiments were carried out on rats of both sexes of the Wistar strain weighing 160-170 g. The calendula-6 antiexudative activity was determined on a model of acute aseptic inflammation of the hind limb of rats using the phlogogenic agent formalin. Reproduction of acute aseptic inflammation of the limb was carried out according to the method of Yu.V. Strelnikov [Guide to the experimental (preclinical) study of new pharmacological substances. - M., 2005. 832 p.]. Decoctions “Calendula-6”, FGH (experimental group) and distilled water (control group) were administered intragastrically in a volume of 1 ml / 100 g of animal weight 3 hours before subplant implantation in rats in the right hind paw of 0.1 ml of 3% formalin solution, and then 5 and 18 hours after that. 24 hours after the introduction of formalin, the antiexudative effect of the phytobox was evaluated by the oncometric method. The data obtained are given in table.3

Table 3
The influence of the decoction of the collection "Calendula-6" on the phase of exudation with "formalin" edema of the paws of rats №№ Experience Conditions The volume of displaced water, ml Percent inhibition of edema before formalin after administration of formalin one Control (H ₂ O) 0.64 ± 0.03 0.98 ± 0.05 - 2 Calendula 6 0.85 ± 0.06 1.02 ± 0.04 * 33% 3 FHK 0.76 ± 0.05 0.95 ± 0.07 * 28%

The broth collection "Calendula-6" has an antiexudative effect, reducing swelling of the paws of rats by 33% compared with rats in rats of the control group (table 3).

To study the effect of Calendula-6 on the phase of the inflammatory process alteration, experiments were carried out on rats of both sexes of the Wistar strain weighing 150-170 g. The inflammatory process was reproduced according to the method of Menkin [Guide to the experimental (preclinical) study of new pharmacological substances. - M., 2005. - 832 S.] by subcutaneous injection of 0.5 ml of a 9% solution of acetic acid in the back with a pre-trimmed coat. At the same time, rats were injected intraperitoneally with a solution of dextran in a dose of 300 mg / kg. The first intragastric administration of "Calendula-6" in a volume of 1 ml / 200 g was carried out 1 hour before the introduction of acetic acid, and then daily once a day for 29 days. Animals of the control group received water purified in a similar way in equivalent volumes. On the 9th, 20th, 29th day of the experiment, the area of necrotic tissue was estimated by the planimetric method. The data obtained are given in table.4.

Table 4
The effect of the complex phyto-drug "Calendula-6" on the phase of alteration of the inflammatory reaction №№ Experience Conditions The area of necrotic tissue, cm ² 9th day 20th day 29th day one Control (H ₂ O) 3.61 ± 0.38 2.42 ± 0.13 1.50 ± 0.11 2 Calendula 6 2.82 ± 0.20 1.95 ± 0.15 * 1.06 ± 0.11 * 3 FHK 2.21 ± 0.23 1.91 ± 0.16 0.94 ± 0.09 *

The course introduction of "Calendula-6" within 29 days reduces the degree of tissue damage when exposed to a phlogogenic agent and significantly reduces the area of the ulcer surface. So, after 9 and 20 days after the introduction of acetic acid, the alteration area decreased by 39 and 21%, respectively, compared with the indices in rats of the control group. A more pronounced anti-inflammatory effect of the test drug was observed on the 29th day, when the alteration area decreased by 37%, the comparison drug has a less pronounced anti-alterative effect (Table 4).

To study the effect of Calendula-6 on proliferative processes in the inflammatory process, experiments were carried out on rats of the Wistar strain of both sexes weighing 170-180 g. The inflammatory reaction was induced by the method of Trinus et al. [Guide to the experimental (preclinical) study of new pharmacological substances. - M., 2005. - 832 p.]. For this, sterile cotton balls weighing 15 mg were implanted under the skin of rats in the back region under aseptic conditions. Decoctions of the collections were administered intragastrically in a volume of 1 ml / 100 g once a day for 7 days. The animals of the control group were injected in equivolume amounts according to a similar scheme with purified water. After 7 days, granulomas were removed and weighed on an analytical balance in raw form (immediately after extraction) and after drying at a temperature of 70 ° C for 24 hours to constant weight. The proliferative reaction was evaluated by the difference between the mass of dry granulomas and the initial mass of a cotton ball, antiexudative activity - by the difference between the mass of wet and dry granulomas. The data obtained are given in table.5.

Table 5
The influence of the decoction of the collection "Calendula-6" on the proliferation phase of the inflammatory reaction Experience Conditions Control (H ₂ O) Calendula 6 FHK Wet balls mg 198 ± 4.2 150 ± 0.7 139.3 ± 8.3 Dry balls mg 32.1 ± 2.7 34.3 ± 1.2 25.3 ± 1.8 The difference from the initial mass, mg 17.1 19,4 10.3

The experimental data shown in Table 6 indicate that Calendula-6, compared with the collection of FHC, has a more beneficial effect on the formation of fibro-granulation tissue in the phase of chronic proliferative inflammation in rats.

Thus, the data of the studies show that the test collection "Calendula-6" has a more pronounced anti-inflammatory effect compared with the comparison drug.

3. The study of the influence of "Calendula-6" on the condition of patients with chronic alcoholism (clinical observations).

Shredded and sifted through a sieve with a diameter of 2.0 mm inflorescences of calendula officinalis 3.0 g; peppermint leaves 1.0 g; Scutellaria baicalensis roots 2.0 g; rhizomes of frankincense 1.0 g; leaves black berry frangipani 1.0 g; Shrubs of a five-leaved shrub 2.0 g mixed. Calendula-6 decoction for clinical trials was prepared in the form of tea: 1 teaspoon of the mixture was placed in an infundira apparatus, 100 ml of boiled water was added, heated in a water bath, maintaining boiling for 30 minutes. After cooling for 10 minutes, the extract is filtered through gauze or a piece of cotton, and the resulting filtrate is used for clinical studies.

A clinical study of the effectiveness of this herbal remedy was conducted in 2001-2003 on the basis of the Republican Narcological Dispensary in Ulan-Ude. We examined 150 patients with alcoholism among men aged 21 to 47 years, 54 men who consumed ethanol sporadically (Table 6). Patients according to the duration of the disease were divided into 2 groups: 1 group - the duration of the disease up to 5 years; Group 2 - the duration of the disease from 6 to 11 years or more. In turn, patients who were divided into 2 groups according to the duration of the disease were divided into another 2 subgroups: in addition to the same detoxification treatment, they took Calendula-6 (subgroup A) and the second subgroup of patients who did not take Calendula-6 "(Subgroup B). All patients were diagnosed with II advanced stage of alcoholism, the duration of drinking bout 14-20 days. According to the medical history, almost all patients showed signs of alcoholic liver damage during a clinical examination: a sharp decrease in appetite, nausea, vomiting, tongue overlay, pain and heaviness in the right hypochondrium, hepatomegaly, yellowness of the skin, icteric sclera, the presence of bile pigments in the urine .

Table 6
Clinical characteristics of patients Distribution of patients by parameters The number of patients, abs. (%) 1. Age, years 21-30 19 (12.7) 31-39 52 (34.7) 40-49 79 (52.6) 2. The duration of the disease, years Up to 5 42 (28.0) 6 to 11 31 (20.7) More than 11 23 (15.3) Alcohol drinkers occasionally 54 (36.0)

All patients received the same type of detoxification treatment; no other agents affecting the hepatobiliary system were prescribed. Patients took "calendula-6" 100 ml in the form of tea 3 times a day for 7 days. To determine the functional state of the liver, the activity of certain biochemical parameters of blood serum in patients was determined. To assess the significance of differences between the mean values of the sample, the nonparametric Wilkinson test (Mann-Whitney) was used [K. Lakin Krylov Yu.F. Biotransformation of drugs: general issues. M .: Medicine. 1981. 342 p.]. In addition to biochemical parameters, information on the course of treatment with Calendula-6 was recorded in a special clinical observation map. A scoring of each sign was carried out: 0 - absence, 1 - weak severity, 2 - medium, 3 - strong severity. Survey data are shown in tables 7 and 8.

Table 7
The effect of "calendula-6" on the clinical signs of hepatotoxicity in patients with chronic alcoholism lasting up to 5 years Clinical signs Before treatment The effectiveness of treatment in points * 3rd day of treatment 5th day of treatment 7th day of treatment subgroup subgroup subgroup BUT B BUT B BUT B Pain and heaviness in the right hypochondrium 3.0 2.5 2.5 1,5 1.8 0 1,0 Liver enlargement 2,3 2.2 2.2 2.0 2.0 1.8 2.0 Yellowness of the skin 2.0 1.8 2.0 1,6 1.8 1,2 1,6 Icterus sclera 2,4 2.2 2,4 1.8 2.0 1.2 1.8 The presence of bile pigments in the urine 2,8 2.2 2,4 1,5 1,5 0 1,0 Note: subgroup A - patients who received detoxification therapy + "calendula-6"; subgroup B - patients who received the same type of detoxification therapy. * - assessment of the severity of symptoms in points: 0 - absent; 1 - poorly expressed; 2 - moderately expressed; 3 - strongly expressed

When analyzing the results of evaluating the effectiveness of Calendula-6, its ability to affect pain and heaviness in the right hypochondrium was primarily determined. As a result of the examination, in most cases, already from the 3rd day, a noticeable effect of Calendula-6 on the severity and pain in the right hypochondrium was noted. By the 7th day, pain was completely absent (Table 8). From the 3rd day, a tendency toward a decrease in other clinical signs was also clearly observed.

Table 8
The effect of "Calendula-6" on the clinical signs of hepatotoxicity in patients with chronic alcoholism lasting from 6 to 11 years or more Days of treatment Clinical signs Pain and heaviness in the right hypochondrium Liver enlargement Yellowness of the skin Icterus sclera The presence of bile pigments in the urine The effectiveness of therapy in points * Before treatment 3.0 2,8 2.6 2,8 3.0 3rd day subgroup A 2,8 2,8 2.6 2,4 2.2 subgroup B 2,8 2,8 2.6 2.6 2,8 5th day subgroup A 2,4 2.6 2,4 2.2 1.8 subgroup B 2,4 2.6 2.2 2,4 2,8 7th day subgroup A 1,2 2,4 1.8 1,6 1,2 subgroup B 1,5 2.6 2.0 2.0 1.8 Note: subgroup A - patients who received detoxification therapy + "calendula-6"; subgroup B - patients who received the same type of detoxification therapy. * - assessment of the severity of symptoms in points: 0 - absent; 1 - poorly expressed; 2 - moderately expressed; 3 - strongly expressed.

The effect of "Calendula-6" on clinical signs in patients with a disease duration of up to 10 years or more also had a positive trend, although clinical symptoms persist longer than in patients of group I (Table 7). Table 9 shows the data of biochemical analyzes of patients during treatment with "calendula-6."

The dynamics of changes in blood biochemical parameters was characterized in the following: the activity of ACT enzymes in blood serum decreased by 41-43% during treatment with Calendula-6 phyto-collection, and AlT by 45-59% (Table 9). In patients of group B who did not take the studied herbal remedy, respectively, AcT decreased by 32-36%, ALT by 38-50%. We also clearly observed a decrease in cholesterol, alkaline phosphatase, and β-lipoproteins by 1.5 times, and the bilirubin content by 4 times. Indicators of total protein and thymol test approached those of patients in the control group (occasionally consumed) (Table 9).

Thus, the use of the Calendula-6 phyto collection for the prevention and treatment of alcoholic liver damage in patients with chronic alcoholism under clinical conditions made it possible to correct the main symptoms of liver damage and normalize its functional state.

It is known that alcohol intoxication of the body is accompanied by a pronounced activation of free radical oxidation of lipids in the biological membranes of liver cells [C. Loguerco, A. Federico. Oxidative stress in viral and alcoholic hepatitis.// Free Rad. Biol. and Med. 2003. 34. No 1. P.3-10]. In order to study the intensity of lipid peroxidation processes in blood serum, the content of secondary products of lipid peroxidation — malondialdehyde — MDA — was determined. Also, to evaluate the state of the antioxidant defense of the body in serum, the activity of catalase was determined. The research results are presented in table 10.

In the study of lipid peroxidation in the blood serum of patients receiving "Calendula-6", a decrease in the content of MDA by 23-24% was found, while in patients of subgroup B by 17-20%. An increase in catalase activity was also observed in patients of subgroup A by 27-35%, in patients of subgroup B by 10-29%, which indicates activation of the endogenous antioxidant system (Table 10).

Thus, taking into account the experimental and clinical study of “Calendula-6,” its pronounced anti-inflammatory and hepatoprotective effect was established in cases of liver damage by alcohol.

Claims (1)

A medicinal collection possessing hepatoprotective and anti-inflammatory activities based on plant materials of inflorescences of calendula officinalis, peppermint leaves, characterized in that it also contains roots of Scutellaria baicalensis, black leaves and rhizomes of frangipani, shoots of shrubs with five leaves in weight per weight:
Inflorescences of calendula officinalis 3.0 Peppermint leaves 1,0 The roots of Scutellaria baicalensis 2.0 Rhizomes of Badan 1,0 Leaves black frankincense 1,0 Shrubbery Five-Shoots 2.0