WO2020211088A1

WO2020211088A1 - Traditional chinese medicine composition and use thereof

Info

Publication number: WO2020211088A1
Application number: PCT/CN2019/083519
Authority: WO
Inventors: 吴以岭; 吴相君; 贾振华; 吴瑞
Original assignee: 石家庄以岭药业股份有限公司
Priority date: 2019-04-19
Filing date: 2019-04-19
Publication date: 2020-10-22

Abstract

A traditional Chinese medicine composition, prepared from the following traditional Chinese medicine crude drugs in part by weight: 200-300 parts of fructus forsythia, 60-100 parts of herba ephedrae, 40-60 parts of rheum, 200-300 parts of herba houttuyniae, 200-300 parts of flos lonicerae, 200-300 parts of radix isatidis, 60-100 parts of herba pogostemonis, 200-300 parts of rhizoma dryopteris crassirhizomae, 60-100 parts of rhodiola rosea L., 5-9 parts of menthol, 60-100 parts of semen armeniacae amarum, 60-100 parts of radix glycyrrhizae, and 200-300 parts of gypsum. The traditional Chinese medicine composition comprises the following components: 0.4-0.9 mg/g of ephedrine hydrochloride and pseudoephedrine hydrochloride, 2.2-4.3 mg/g of amygdalin, 0.25-0.75 mg/g of chrysophanol, 0.15-0.40 mg/g of rheum emodin, 2.4-5.4 mg/g of chlorogenic acid, 1.4-2.7 mg/g of neochlorogenic acid, 1.6-3.4 mg/g of cryptochlorogenic acid, 2.0-5.5 mg/g of isopsythioside A, 1.65-2.90 mg/g of 4,5-di-o-caffeoylquinic acid, 2.7-3.8 mg/g of quercitrin, 1.4-2.9 mg/g of glycyrrhizic acid, and 2.5-3.4 mg/g of phillyrin. The traditional Chinese medicine composition has the effect of treating cold and upper respiratory infection.

Description

Chinese medicine composition and its use

Technical field

This application relates to the field of medicine, in particular to a traditional Chinese medicine composition and its preparation method and application.

Background technique

Traditional Chinese medicine is the most important material means for preventing and curing diseases in Chinese medicine. Improving the therapeutic effect of Chinese medicine is the key to the therapeutic effect of Chinese medicine. Regarding the characteristics of multi-component and multi-target effects of traditional Chinese medicine, increasing the content of multiple iconic components of traditional Chinese medicine can improve the quality of traditional Chinese medicine.

Summary of the invention

In response to the above technical problems, one or more embodiments of the present application provide a Chinese medicine composition, which is made of the following mass parts of Chinese medicine raw materials: Forsythia (Fructus Forsythia) 200-300, Ephedrae (Herba Ephedrae) 60-100, Rheum (rheum) 40-60, Houttuyniae (Herba Houttuyniae) 200-300, Honeysuckle (Flos Lonicerae) 200-300, Radix Isatidis (Radix Isatidis) 200-300, Huoxiang (Herba Pogostemonis) 60-100, Mianmaguan Public (Rhizoma Dryopteris Crassirhizomae) 200-300, Rhodiola (Rhodiola rosea L.) 60-100, Menthol (menthol) 5-9, Bitter almond (Semen Armeniacae Amarum) 60-100, Licorice (Radix Glycyrrhizae) 60- 100. Gypsum (gypsum) 200-300;

The traditional Chinese medicine composition contains the following ingredients:

0.4-0.9mg/g ephedrine hydrochloride and pseudoephedrine hydrochloride, 2.2-4.3mg/g amygdalin, 0.25-0.75mg/g chrysophanol, 0.15-0.40mg/g emodin, 2.4-5.4mg/ g of chlorogenic acid, 1.4-2.7mg/g of neochlorogenic acid, 1.6-3.4mg/g of cryptochlorogenic acid, 2.0-5.5mg/g of isoforsythoside A, 1.65-2.90mg/g 4,5-Di-O-caffeoylquinic acid, quercetin at 2.7-3.8mg/g, glycyrrhizin at 1.4-2.9mg/g and forsythin at 2.5-3.4mg/g.

The application also provides the use of the traditional Chinese medicine composition in the preparation of medicines for the treatment of colds and upper respiratory tract infections.

Detailed description of the invention

One or more embodiments of the present application provide a traditional Chinese medicine composition, which is made of the following mass parts of traditional Chinese medicine raw materials: forsythia (Fructus Forsythia) 200-300, ephedra (Herba Ephedrae) 60-100, rhubarb (rheum) 40 -60, Herba Houttuyniae 200-300, Flos Lonicerae 200-300, Radix Isatidis 200-300, Herba Pogostemonis 60-100, Rhizoma Dryopteris Crassirhizomae ) 200-300, Rhodiola rosea L. 60-100, Menthol 5-9, Semen Armeniacae Amarum 60-100, Radix Glycyrrhizae 60-100, Gypsum )200-300;

In one or more embodiments of the present application, the traditional Chinese medicine composition contains the following ingredients: 0.4-0.9mg/g ephedrine hydrochloride and pseudoephedrine hydrochloride, 2.2-4.3mg/g amygdalin, 0.25- 0.75mg/g chrysophanol, 0.15-0.40mg/g emodin, 2.4-5.4mg/g chlorogenic acid, 1.4-2.7mg/g neochlorogenic acid, 1.6-3.4mg/g cryptochlorogen Acid, 2.0-5.5mg/g isoficrin A, 1.65-2.90mg/g 4,5-di-O-caffeoylquinic acid, 2.7-3.8mg/g quercetin, 1.4- 2.9mg/g glycyrrhizic acid and 2.5-3.4mg/g forsythin.

In one or more embodiments of the present application, the content of ephedrine hydrochloride and pseudoephedrine hydrochloride contained in the traditional Chinese medicine composition is 0.4 mg/g, 0.5 mg/g, 0.6 mg/g, 0.7 mg/g, 0.8 mg/g Or 0.9mg/g.

In one or more embodiments of the present application, the content of amygdalin contained in the traditional Chinese medicine composition is 2.2 mg/g, 2.5 mg/g, 3 mg/g, 3.5 mg/g, 4 mg/g or 4.3 mg/g .

In one or more embodiments of the present application, the content of chrysophanol contained in the traditional Chinese medicine composition is 0.25 mg/g, 0.3 mg/g, 0.4 mg/g, 0.5 mg/g, 0.6 mg/g, 0.7 mg/g g or 0.75mg/g.

In one or more embodiments of the present application, the content of emodin contained in the traditional Chinese medicine composition is 0.15 mg/g, 0.2 mg/g, 0.3 mg/g or 0.40 mg/g.

In one or more embodiments of the present application, the content of chlorogenic acid contained in the traditional Chinese medicine composition is 2.4 mg/g, 3 mg/g, 4 mg/g, 5 mg/g or 5.4 mg/g.

In one or more embodiments of the present application, the content of neochlorogenic acid contained in the traditional Chinese medicine composition is 1.4 mg/g, 1.6 mg/g, 1.8 mg/g, 2 mg/g, 2.5 mg/g, or 2.7 mg/g. g.

In one or more embodiments of the present application, the content of cryptochlorogenic acid contained in the traditional Chinese medicine composition is 1.6 mg/g, 2 mg/g, 2.5 mg/g, 3 mg/g or 3.4 mg/g.

In one or more embodiments of the present application, the content of isoficrin A contained in the traditional Chinese medicine composition is 2.0 mg/g, 2.5 mg/g, 4 mg/g, 4.5 mg/g, 5 mg/g or 5.5 mg/g.

In one or more embodiments of the present application, the content of di-O-caffeoylquinic acid contained in the traditional Chinese medicine composition is 0.65mg/g, 0.8mg/g, 1mg/g, 1.5mg/g, 1.7mg /g, 1.8mg/g or 1.90mg/g.

In one or more embodiments of the present application, the content of quercetin contained in the traditional Chinese medicine composition is 2.7 mg/g, 3 mg/g, 3.2 mg/g, 3.5 mg/g or 3.8 mg/g.

In one or more embodiments of the present application, the content of glycyrrhizic acid contained in the traditional Chinese medicine composition is 1.4 mg/g, 1.8 mg/g, 2 mg/g, 2.2 mg/g, 2.5 mg/g or 2.9 mg/g .

In one or more embodiments of the present application, the content of forsythin contained in the traditional Chinese medicine composition is 2.5 mg/g, 3 mg/g, 3.1 mg/g, 3.2 mg/g, 3.3 mg/g, or 3.4 mg/g. g.

In one or more embodiments of the present application, the traditional Chinese medicine composition contains the following ingredients: 4.0-5.4 mg/g chlorogenic acid, 2.0-2.7 mg/g neochlorogenic acid, 2.5-3.4 mg /g of cryptochlorogenic acid, 3.5-5.5mg/g of isoforsythoside A, 2.0-2.90mg/g of 4,5-di-O-caffeoylquinic acid, 3.0-3.8mg/g Quercetin and 2.5-2.9mg/g glycyrrhizic acid.

In one or more embodiments of the present application, wherein the ephedra is roasted ephedra, the bitter almond is fried bitter almond, and the ageratum is patchouli.

In one or more embodiments of the present application, wherein the traditional Chinese medicine composition is prepared by the following method:

Weigh the raw materials of Chinese medicine according to the above-mentioned mass ratio;

Extract Huoxiang with 8-10 weight-volume water for 2-4 hours to obtain Huoxiang volatile oil and Huoxiang cream;

Extract forsythia, ephedra, houttuynia cordata and rhubarb together with 50-90% ethanol at a weight-volume ratio of 6-10, and recover the ethanol to obtain the first clear ointment;

The honeysuckle, gypsum, Radix isatidis, Mianma Guanzhong, licorice and Rhodiola are boiled together with 7-11 weight-volume water, add bitter almonds, decoct for 1-4 hours, and combine the obtained extract with the Agastache Mix the clear ointment and concentrate the resulting mixture into a clear ointment, add 95% ethanol to the clear ointment until the ethanol concentration is 60-80%, leave it for 12-24 hours, filter through a ceramic membrane to obtain the filtrate, and recover the ethanol to obtain the second Clear cream

The second clearing paste is mixed with the first clearing paste, the mixture is concentrated under reduced pressure to obtain a paste with a relative density of 1.15 to 1.20, and the paste is vacuum belt dried and crushed to an appropriate particle size , To obtain a dry paste powder, and add menthol and the Huoxiang volatile oil to the dry paste powder to obtain the traditional Chinese medicine composition.

In one or more embodiments of the present application, wherein 85% ethanol is added to the dry paste powder to form granules, which are dried to obtain dry granules; the menthol and the Huoxiang volatile oil are added to the dry granules, After mixing, the capsules are filled to obtain the traditional Chinese medicine composition capsules.

In one or more embodiments of the present application, forsythia, ephedra, houttuynia cordata and rhubarb are extracted together with 6-10 weight-volume 70% ethanol for 1-2 times, each for 1-2 hours.

In one or more embodiments of the present application, honeysuckle, gypsum, Isatis indigotica, Mianma Guanzhong, licorice and Rhodiola rosea are boiled together with water at a weight-volume ratio of 7-11, bitter almonds are added, and decocted for 1-2 Seconds, for 1-2 hours each time, mix the obtained extract with the Huoxiang clear ointment and concentrate the resulting mixture into a clear ointment with a relative density of 1.10-1.15.

In one or more embodiments of the present application, 95% ethanol is added to the clear ointment until the ethanol concentration is 70%, and it is left at room temperature for 12-24 hours.

One or more embodiments of this application provide a method for preparing the traditional Chinese medicine composition of this application.

Weigh the raw materials of Chinese medicine according to the following mass ratios: Forsythia (Fructus Forsythia) 200-300, Ephedrae (Herba) 60-100, Rheum (rheum) 40-60, Houttuyniae (Herba Houttuyniae) 200-300, Honeysuckle (Flos Lonicerae) 200-300, Radix Isatidis 200-300, Huoxiang (Herba Pogostemonis) 60-100, Rhizoma Dryopteris Crassirhizomae 200-300, Rhodiola Rosea L.) 60 -100, menthol (menthol) 5-9, bitter almond (Semen Armeniacae Amarum) 60-100, licorice (Radix Glycyrrhizae) 60-100, gypsum (gypsum) 200-300;

The honeysuckle, gypsum, Radix isatidis, Mianma Guanzhong, licorice and Rhodiola are boiled together with 7-11 weight-volume water, add bitter almonds, decoct for 1-4 hours, and combine the obtained extract with the Agastache The clear paste is mixed and the resulting mixture is concentrated into a clear paste, 95% ethanol is added to the clear paste until the ethanol concentration is 60-80%, and it is left at room temperature for 12-24 hours. The filtrate is filtered through a ceramic membrane, and the ethanol is recovered to obtain the third Erqing cream

The second clearing paste is mixed with the first clearing paste, the mixture is concentrated under reduced pressure to obtain a paste with a relative density of 1.15 to 1.20, and the paste is vacuum-belt dried and crushed to obtain a dry paste powder , Adding menthol and the volatile oil of Huoxiang to the dry powder to obtain the traditional Chinese medicine composition.

One or more embodiments of the present application provide the use of the traditional Chinese medicine composition of the present application in the preparation of a medicine for the treatment of colds and upper respiratory tract infections.

In one or more embodiments of the present application, wherein the common cold is influenza and the upper respiratory tract infection is tonsil inflammation.

In one or more embodiments of the present application, the weight-to-volume ratio (Kg/L or g/mL) represents the volume (L or mL) of the solvent used for extraction corresponding to the weight (Kg or g) of the medicinal material.

The traditional Chinese medicine composition in one or more embodiments of the present application is used to treat a cold or upper respiratory tract infection.

The traditional Chinese medicine composition in one or more embodiments of the present application is used to treat influenza or tonsil inflammation.

In one or more embodiments of the present application, the second clear paste is obtained by filtering through a ceramic membrane. Generally, ceramic membrane filtration can be carried out by standing at room temperature. Using ceramic membrane filtration, the impurity removal effect is better, the extraction liquid filtration effect is better, and the content of active ingredients is increased. Using it to filter the original liquid has better filtering effect and better impurity removal effect.

In one or more embodiments of the present application, after mixing the second clearing cream and the first clearing cream, the paste is obtained by filtration under reduced pressure. Not limited to any theoretical limitation, the temperature in the vacuum filtration process is reduced, the time is shortened, and the active ingredient is less damaged.

In one or more embodiments of the present application, the vacuum belt drying temperature is low and the speed is high, so the effective ingredients can be protected well.

In one or more embodiments of the present application, Fructus Forsythia is the dried fruit of Forsythia suspensa (Thunb.) Vahl, a plant of the family Oleaceae.

In one or more embodiments of this application, Ephedrae (Herba Ephedrae) is a dry grass stem of Ephedra sinica Stapf, Ephedra intermedia Schrenk et C.A. Mey. or Ephedra equiisetina Bge.

In one or more embodiments of this application, rheum (rheum) is the dried root of Rheum palmatum L., Rheum tanguticum Maxim. ex Balf. or medicinal Rheum officinale Baill. rhizome.

In one or more embodiments of the present application, Houttuyniae (Herba Houttuyniae) is the dry aerial part of Houttuynia cordata Thunb.

In one or more embodiments of the present application, Flos Lonicerae is Lonicera japonica Thunb., Lonicera hypoglauca Miq., Lonicera confusa DC. or Hairy style. The dry buds of Lonicera dasystyla Rehd. or the first blooming flowers.

In one or more embodiments of the present application, Radix Isatidis is the dry root of Isatis indigotica Fort., a cruciferous plant.

In one or more embodiments of this application, Herba Pogostemonis is Pogostemon cablin (Blanco) Benth. or Agastache rugosa (Fisch.et Mey.) O. Ktze.) The dry aerial part.

In one or more embodiments of the present application, Rhizoma Dryopteris Crassirhizomae is the dry rhizome and petiole residues of Dryopteris Crassirhizoma Nakai, a plant of the Dryopteris family.

In one or more embodiments of the present application, Rhodiola rosea is the dry aerial part of Rhodiola saera (Prain) Fu, a plant of the genus Rhodiola of the Crassulaceae family.

In one or more embodiments of the present application, menthol (menthol) is an aromatic oil obtained by distillation of fresh stems and leaves of Mentha haplocalyx Briq.

In one or more embodiments of this application, bitter almond (Semen Armeniacae Amarum) is a Rosaceae plant Prunus armeniaca L.var.ansu Maxim., Siberian apricot (Mountain apricot) Prunus sibirica L., The dried mature seeds of Prunus mandshurica (Maxim.) Koehne or Prunus armeniaca L..

In one or more embodiments of the present application, licorice (Radix Glycyrrhizae) is the dried root of the legume Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L. of the leguminous family.

In one or more embodiments of the present application, gypsum (gypsum) is a sulfate mineral anhydrite group gypsum, and the main component is hydrous calcium sulfate (CaSO ₄ ·2H ₂ O).

detailed description

Preparation Example 1

1. Weigh the selected Chinese medicinal materials according to the following weight ratios: Forsythia 200, Honeysuckle 300, Isatis root 200, Rhubarb 40, Patchouli 60, Mianma Guanzhong 300, Rhodiola 100, Menthol 9, Ephedra 60 , Bitter Almond 100, Houttuynia Cordata 200, Licorice 100, Gypsum 200;

2. Add 10 weight-volume water to the patchouli, extract the volatile oil by boiling, extract the volatile oil for 4 hours, collect the patchouli volatile oil, filter the extract to obtain a patchouli cream for later use, and discard the residue;

3. Extract forsythia, ephedra, houttuynia cordata and rhubarb with 90% ethanol at a ratio of 10 weight by volume for 2 times, the first time is 2 hours, the second time is 1.5 hours, the extract is filtered, the filtrates are combined, and the ethanol is recovered The first clear ointment is reserved;

4. Add 11 weight-volume water to honeysuckle, gypsum, Radix isatidis, Mianma Guanzhong, licorice and rhodiola, and boil until boiling, add bitter almonds, decoc 2 times, 1.5 hours for the first time, and 1 for the second time. After hours, the extract was filtered, and the filtrate was added to the patchouli clear ointment obtained in step 2, and concentrated into a clear ointment with a relative density of 1.15. 95% ethanol was added and stirred while adding until the alcohol concentration was 70%. After hours, the second clear ointment is obtained by filtering through a ceramic membrane and recovering ethanol from the filtrate until there is no alcohol flavor. The paste is vacuum belt-dried and crushed to obtain dry paste powder;

5. Add an appropriate amount of 85% ethanol to the dry paste powder to make granules, and dry them to obtain dry granules;

6. Dissolve the menthol and the patchouli volatile oil obtained in step 2 with an appropriate amount of ethanol and spray them into the dry particles obtained in step 5, mix them, and fill them into capsules to obtain capsules of traditional Chinese medicine composition.

Preparation Example 2

1. Weigh the selected Chinese medicinal materials according to the following weight ratios: Forsythia 300, Honeysuckle 200, Isatis root 300, Rhubarb 60, Patchouli 100, Mianma Guanzhong 200, Rhodiola 60, Menthol 5, Ephedra 100 , Bitter Almond 60, Houttuynia 300, Licorice 60, Gypsum 300;

2. Add 8 weight-volume water to the patchouli to extract the volatile oil, extract the volatile oil for 4 hours, collect the patchouli volatile oil, filter the extract to obtain a patchouli cream for later use, and discard the residue;

3. Extract forsythia, ephedra, houttuynia cordata and rhubarb with 6 weight-volume 60% ethanol for 2 times, the first time is 2 hours, the second time is 1.5 hours, the extract is filtered, the filtrates are combined, and the ethanol is recovered The first clear ointment is reserved;

4. Add 7 weight-volume water to honeysuckle, gypsum, Radix isatidis, Mianma Guanzhong, licorice and rhodiola, and boil until boiling, add bitter almonds, decoc 2 times, first 1.5 hours, second 1 After hours, filter the extract, add the filtrate to the patchouli cream obtained in step 2, and concentrate it into a cream with a relative density of 1.10. Add 95% ethanol and stir while adding until the alcohol concentration is 70%. Place at room temperature for 24 hours. After hours, the second clear ointment is obtained by filtering through a ceramic membrane and recovering ethanol from the filtrate until there is no alcohol smell. The second clearing ointment is combined with the first clearing ointment obtained in step 3, and concentrated under reduced pressure to a paste with a relative density of 1.15. The paste is vacuum belt-dried and crushed to obtain dry paste powder;

Preparation Example 3

1. Weigh the selected Chinese medicinal materials according to the following weight ratio: Forsythia 278, Honeysuckle 294, Isatis root 285, Rhubarb 55, Patchouli 95, Mianma Guanzhong 290, Rhodiola 87, Menthol 8.5, Ephedra 88 , Bitter Almond 80, Houttuynia Cordata 284, Licorice 95, Gypsum 277;

2. Add 9 weight-volume water to the patchouli to extract the volatile oil, extract the volatile oil for 4 hours, collect the patchouli volatile oil, filter the extract to obtain a patchouli cream for later use, and discard the residue;

3. Extract forsythia, ephedra, houttuynia cordata and rhubarb with 6 weight-volume 80% ethanol for 2 times, the first time is 2 hours, the second time is 1.5 hours, the extract is filtered, the filtrates are combined, and the ethanol is recovered The first clear ointment is reserved;

4. Add 10 weight-volume water to honeysuckle, gypsum, Radix isatidis, Mianma Guanzhong, licorice and Rhodiola and boil until boiling, add bitter almonds, decoc 2 times, first 1.5 hours, second 1 After hours, filter the extract, add the filtrate to the patchouli cream obtained in step 2, and concentrate it into a cream with a relative density of 1.10. Add 95% ethanol and stir while adding until the alcohol concentration is 70%. Place at room temperature for 24 hours. After hours, the second clear ointment is obtained by filtering through a ceramic membrane and recovering ethanol from the filtrate until there is no alcohol smell. The second clearing ointment is combined with the first clearing ointment obtained in step 3, and concentrated under reduced pressure to a paste with a relative density of 1.15. The paste is vacuum belt-dried and crushed to obtain dry paste powder;

Preparation Example 4

1. Weigh the selected Chinese herbal medicines according to the following weight ratios: Forsythia 255, Honeysuckle 255, Isatis root 255, Rhubarb 51, Patchouli 85, Mianma Guanzhong 255, Rhodiola 85, Menthol 7.5, Ephedra 85 , Bitter Almond 85, Houttuynia 255, Licorice 85, Gypsum 255;

Comparative Example 1

4. Add 11 weight-volume water to honeysuckle, gypsum, Radix isatidis, Mianma Guanzhong, licorice and rhodiola, and boil until boiling, add bitter almonds, decoc 2 times, 1.5 hours for the first time, and 1 for the second time. After hours, filter the extract, add the filtrate to the patchouli cream obtained in step 2, and concentrate it into a clear cream with a relative density of 1.15. Add 95% ethanol and stir while adding until the alcohol concentration is 70%. Place at room temperature for 24 hours. After hours, the second clear ointment is obtained by filtering through the plate and frame and recovering ethanol from the filtrate until there is no alcohol. Combine the second clear ointment with the first clear ointment obtained in step 3, and concentrate to a paste with a relative density of 1.20 under normal pressure. The paste is spray-dried at 45-48°C to obtain dry paste powder;

Comparative Example 2

4. Add 7 weight-volume water to honeysuckle, gypsum, Radix isatidis, Mianma Guanzhong, licorice and rhodiola, and boil until boiling, add bitter almonds, decoc 2 times, first 1.5 hours, second 1 After hours, filter the extract, add the filtrate to the patchouli cream obtained in step 2, and concentrate it into a cream with a relative density of 1.10. Add 95% ethanol and stir while adding until the alcohol concentration is 70%. Place at room temperature for 24 hours. After hours, filter through the plate and frame and recover the ethanol from the filtrate until there is no alcohol to obtain the second clear paste. Combine the second clear paste with the first clear paste obtained in step 3, and concentrate it to a paste with a relative density of 1.15 under normal pressure. The paste is spray-dried at 45-48°C to obtain dry paste powder;

Comparative Example 3

4. Add 10 weight-volume water to honeysuckle, gypsum, Radix isatidis, Mianma Guanzhong, licorice and Rhodiola and boil until boiling, add bitter almonds, decoc 2 times, first 1.5 hours, second 1 After hours, filter the extract, add the filtrate to the patchouli cream obtained in step 2, and concentrate it into a cream with a relative density of 1.10. Add 95% ethanol and stir while adding until the alcohol concentration is 70%. Place at room temperature for 24 hours. After hours, filter through the plate and frame and recover the ethanol from the filtrate until there is no alcohol to obtain the second clear paste. Combine the second clear paste with the first clear paste obtained in step 3, and concentrate it to a paste with a relative density of 1.15 under normal pressure. The paste is spray-dried at 45-48°C to obtain dry paste powder;

Comparative Example 4

Assay Examples

Chromatographic conditions

Waters Acquity UPLC HSS T3 (column length is 100mm, inner diameter is 2.1mm, particle size is 1.8μm) chromatographic column, using methanol-acetonitrile-0.1% phosphoric acid as mobile phase, gradient elution is performed as follows, detection wavelength is 239nm, The flow rate is 0.3ml/min.

Mobile phase gradient elution

Preparation of reference solution

Take an appropriate amount of ephedrine hydrochloride and pseudoephedrine hydrochloride reference substance, accurately weigh it, add methanol-water (containing 0.092% phosphoric acid, 0.04% triethylamine and 0.02% di-n-butylamine) 10:90 to make 30μg ephedrine hydrochloride per 1mL And 8μg pseudoephedrine hydrochloride mixed solution, that is.

Take an appropriate amount of amygdalin reference substance, accurately weigh it, and add the mobile phase (methanol-acetonitrile-0.1% phosphoric acid) to make a solution containing 161.85 μg per 1 mL, and get it.

Take an appropriate amount of chrysophanol and emodin reference substance, accurately weigh it, and add methanol to make a mixed reference substance solution containing 64μg chrysophanol and 29μg emodin per 1mL, and get it.

Take neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isoforsythoside A, 4,5-di-O-caffeoylquinic acid, quercetin, ammonium glycyrrhizinate reference substance (glycyrrhizic acid weight = licorice Ammonium acid weight/1.0207, calculate the amount of glycyrrhizic acid based on this) appropriate amount, accurately weighed, and add 50% methanol to make 30.86μg neochlorogenic acid, 77.55μg chlorogenic acid, 33.66μg cryptochlorogenic acid, 95.52μg per 1mL A mixed solution of isforsythoside A, 29.75μg 4,5-di-O-caffeoylquinic acid, 22.67μg quercetin and 42.92μg ammonium glycyrrhizinate, namely (glycyrrhizic acid weight = ammonium glycyrrhizinate weight / 1.0207 ).

Take an appropriate amount of forsythin reference substance, accurately weigh it, add 50% methanol to make a reference substance solution containing 6 μg per 1 mL, and get it.

Preparation of test solution

Take an appropriate amount of the contents of the traditional Chinese medicine composition capsules prepared in the above Preparation Example 1-4 and Comparative Example 1-4, grind it into fine pieces, take 0.25g, accurately weigh it, place it in a stoppered conical flask, and accurately add 50% methanol 25mL, weigh it, ultrasonic treatment (power 500W, frequency 40kHz) for 30 minutes, let it cool, then weigh it, use 50% methanol to make up the lost weight, shake well, filter, and take the additional filtrate to get it.

Assay

Precisely draw 2μL each of each reference solution and test solution, and inject it into a high-performance liquid chromatograph for determination. Calculate the ephedrine hydrochloride, pseudoephedrine hydrochloride, amygdalin, chrysophanol, emodin, chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, isoforsythiaside A, 4,5-di-O- in each sample The contents of caffeoylquinic acid, quercetin, glycyrrhizin and forsythin are shown in the following tables.

Table 1 Total content of ephedrine hydrochloride and pseudoephedrine hydrochloride

Table 2 Amygdalin content

Table 3 The content of chrysophanol and emodin

Table 4 Chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, isoforsythoside A, quercetin, 4,5-di-O-caffeoyl

Table 5 Forsythin content

It can be seen from Table 1 to Table 5 that the ephedrine hydrochloride, pseudoephedrine hydrochloride, amygdalin, chrysophanol, emodin, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, and isoforsythiae in preparation examples 1-4 The contents of glycoside A, 4,5-di-O-caffeoylquinic acid, quercetin, glycyrrhizin, and forsythin were all increased compared to Comparative Examples 1-4.

Active Example

In order to compare the clinical efficacy of the Chinese medicinal composition of the comparative example and the Chinese medicinal composition of this application in anti-flu, treating colds, and treating tonsillitis, the methods of Comparative Example 1 and Preparation Example 1 were used to obtain sample A and sample B, respectively. Perform the following clinical trials.

1 clinical data

1.1 Diagnostic criteria

Refer to the "Guiding Principles for Clinical Research of New Chinese Medicines · Guidelines for Clinical Research of New Chinese Medicines for the Treatment of Colds"; the Ministry of Health "Influenza Diagnosis and Treatment Guidelines" (the Ministry of Health's Influenza Diagnosis and Treatment Guidelines Compilation Expert Group, 2011 edition, Community Medicine Journal, 2011, 9(5): 66-74) established the diagnostic criteria for influenza; the national planning textbook "Otorhinolaryngology and Neck Surgery" (Tian Yongquan, People Health Publishing House, 7th Edition, 2009) and "Guidelines for the Diagnosis and Treatment of Common Diseases in Traditional Chinese Medicine Otorhinolaryngology" (Chinese Society of Traditional Chinese Medicine, China Traditional Chinese Medicine Publishing House, 2012).

1.2 General information

Taking cold, influenza and tonsillitis patients in the outpatient clinic of Yiling Hospital of Hebei Province as the research object, they were randomly divided into sample A group and sample B group with 84 cases each by using the digital table method.

Sample group A: 54 males and 30 females; aged 15-63 years old, with an average age of 37 years.

Sample group B: 52 males and 32 females; age 13-64 years old, average age 38 years old.

The gender, age, physical condition and medical history of the two groups were statistically processed, and the differences were not significant (P>0.05) and were comparable.

2 treatment methods

The two groups of patients were given corresponding care and the doctor ordered to drink more water. Patients in the sample group A were given sample A; patients in the sample B group were given sample B; both groups were treated for 7 consecutive days. The scores of TCM syndromes, the time of medicine to relieve fever and the disappearance time of pus spots were recorded and compared before and after treatment. .

3 Observation indicators and efficacy standards

3.1 Curative effect observation index

3.1.1 TCM syndrome points

Observe the patient’s symptoms before treatment and 7 days after treatment (fever, nasal congestion, runny nose, nausea or chills, sore throat, etc.), referring to the classification and quantification of common symptoms in the "Guiding Principles for Clinical Research on New Chinese Medicines" (2000) Table, the proposed symptom score, 0 points for asymptomatic, 1 point for mild symptoms, 2 points for moderate symptoms, and 3 points for severe symptoms. See Appendix 6 for details.

Table 6 TCM Syndrome Score Sheet

3.1.2 Action time of drugs to relieve fever

Record the onset time, antipyretic time and healing time of the drug. The onset time is the time required for the body temperature to decrease by 0.5°C after taking the medicine. Antipyretic time is the time required for body temperature to drop to 37°C after taking the medicine. The recovery time is the time required for the clinical symptoms to disappear completely after taking the medicine.

3.1.3 Time of pus disappearance

Observe and compare the disappearance time of pus spots in the two groups.

3.2 Efficacy evaluation criteria

Refer to the "Diagnosis and Efficacy Standards for Diseases and Symptoms of Traditional Chinese Medicine" (National Administration of Traditional Chinese Medicine·Diagnosis and Efficacy Standards for Diseases of Traditional Chinese Medicine, Beijing: China Medical Science and Technology Press, 2012.11) and "Guiding Principles for Clinical Research of New Chinese Medicines" (Zhonghua Ministry of Health of the People's Republic of China. Guidelines for Clinical Research of New Chinese Medicines (First Series), Beijing: China Medical Science and Technology Press, 1993.11).

Healed: symptoms disappear, body temperature is normal, main symptom score is reduced by ≥95%; markedly effective: symptoms are significantly improved, body temperature is normal, 70%≤main symptom score reduction is less than 95%; effective: symptoms are slightly improved, body temperature is below 38°C, 30%≤ The main symptom score decreased by <70%; invalid: the symptoms were not significantly improved or worsened, the main symptom score decreased by <30%. Total effective rate=(number of cured cases+number of markedly effective cases+number of effective cases)/n×100%.

3.3 Treatment results

3.3.1 Comparison of symptom scores before and after treatment between the two groups

Table 7

In terms of symptom score improvement before and after treatment, the sample B group has more clinical advantages than the sample A group, and the difference is statistically significant (P<0.05).

3.3.2 Comparison of the time for the two groups of drugs to relieve fever

Table 8

In terms of onset time of drug action, there was no statistically significant difference between sample B group and sample A group (P>0.05).

3.3.3 The disappearance time of pus spots in the two groups

Table 9

The disappearance of pus spots in sample B group was shorter than that in sample A, and the difference was statistically significant (P<0.05).

3.3.4 Comparison of clinical efficacy between the two groups of patients (number of cases)

Table 10

The total effective rate of sample B group was significantly better than that of sample A group, and the difference was statistically significant (P<0.05).

3.3.5 Safety evaluation

In this clinical observation, the patients in the sample A group and the sample B group did not have serious adverse reactions and allergic symptoms; before and after treatment, the patients' general physical examination, blood and urine routine, and liver and kidney functions were all within the normal range.

4 Conclusion

Observation shows that the sample B obtained by the preparation method of Preparation Example 1 has a definite anti-flu, cold, and tonsillitis curative effect. Compared with the sample A obtained in Comparative Example 1, the clinical treatment effect is better, and no adverse reactions occur.

Claims

Chinese medicine composition, which is made of Chinese medicine raw materials of the following parts by mass: Forsythia 200-300, Ephedra 60-100, Rhubarb 40-60, Houttuynia 200-300, Honeysuckle 200-300, Radix Isatidis 200-300, Huoxiang 60-100, Mianma Guanzhong 200-300, Rhodiola 60-100, Menthol 5-9, Bitter Almond 60-100, Licorice 60-100, Gypsum 200-300;

The traditional Chinese medicine composition contains the following ingredients:

0.4-0.9mg/g ephedrine hydrochloride and pseudoephedrine hydrochloride, 2.2-4.3mg/g amygdalin, 0.25-0.75mg/g chrysophanol, 0.15-0.40mg/g emodin, 2.4-5.4mg/ g of chlorogenic acid, 1.4-2.7mg/g of neochlorogenic acid, 1.6-3.4mg/g of cryptochlorogenic acid, 2.0-5.5mg/g of isoforsythoside A, 1.65-2.90mg/g 4,5-Di-O-caffeoylquinic acid, quercetin at 2.7-3.8mg/g, glycyrrhizin at 1.4-2.9mg/g and forsythin at 2.5-3.4mg/g.
The traditional Chinese medicine composition according to claim 1, wherein the traditional Chinese medicine composition contains the following ingredients: 4.0-5.4 mg/g chlorogenic acid, 2.0-2.7 mg/g neochlorogenic acid, 2.5-3.4 mg/g g of cryptochlorogenic acid, 3.5-5.5mg/g of isoforsythoside A, 2.0-2.90mg/g of 4,5-di-O-caffeoylquinic acid, 3.0-3.8mg/g of quercetin Cortin and 2.5-2.9mg/g glycyrrhizic acid.
The traditional Chinese medicine composition according to claim 1 or 2, wherein the ephedra ephedra is roasted ephedra, the bitter almond is fried bitter almond, and the huoxiang is patchouli.
The traditional Chinese medicine composition according to claim 1, wherein the traditional Chinese medicine composition is prepared by the following method:

Weigh the raw materials of Chinese medicine according to the above-mentioned mass ratio;

Extract Huoxiang with 8-10 weight-volume water for 2-4 hours to obtain Huoxiang volatile oil and Huoxiang cream;

Extract forsythia, ephedra, houttuynia cordata and rhubarb together with 50-90% ethanol at a weight-volume ratio of 6-10, and recover the ethanol to obtain the first clear ointment;

The honeysuckle, gypsum, Radix isatidis, Mianma Guanzhong, licorice and Rhodiola are boiled together with 7-11 weight-volume water, add bitter almonds, decoct for 1-4 hours, and combine the obtained extract with the Agastache Mix the clear ointment and concentrate the resulting mixture into a clear ointment, add 95% ethanol to the clear ointment until the ethanol concentration is 60-80%, leave it for 12-24 hours, filter through a ceramic membrane to obtain the filtrate, and recover the ethanol to obtain the second Clear cream

The second clearing paste is mixed with the first clearing paste, the mixture is concentrated under reduced pressure to obtain a paste with a relative density of 1.15 to 1.20, and the paste is vacuum-belt dried and crushed to obtain a dry paste powder , Adding menthol and the volatile oil of Huoxiang to the dry powder to obtain the traditional Chinese medicine composition.
The traditional Chinese medicine composition according to claim 4, wherein 85% ethanol is added to the dry ointment powder to form granules, which are dried to obtain dry granules; the menthol and the Huoxiang volatile oil are added to the dry granules and mixed Then, it is filled into capsules to obtain traditional Chinese medicine composition capsules.
The traditional Chinese medicine composition according to claim 4, wherein the forsythia, ephedra, houttuynia cordata and rhubarb are extracted together with 6-10 weight-volume 70% ethanol for 1-2 times, each for 1-2 hours.
The traditional Chinese medicine composition according to claim 4, wherein the honeysuckle, gypsum, Radix isatidis, Mianma Guanzhong, licorice and Rhodiola are boiled together with water at a weight-volume ratio of 7-11, bitter almonds are added, and decocted for 1-2 Seconds, for 1-2 hours each time, mix the obtained extract with the Huoxiang clear ointment and concentrate the resulting mixture into a clear ointment with a relative density of 1.10-1.15.
The traditional Chinese medicine composition according to claim 4, wherein 95% ethanol is added to the clear ointment until the ethanol concentration is 70%, and it is left for 12-24 hours.
Use of the Chinese medicinal composition of any one of claims 1-8 in the preparation of a medicine for the treatment of colds and upper respiratory tract infections.
The use according to claim 9, wherein the common cold is influenza, and the upper respiratory tract infection is tonsil inflammation.