WO2011113190A1

WO2011113190A1 - Pharmaceutical composition for treating aids and preparation method thereof

Info

Publication number: WO2011113190A1
Application number: PCT/CN2010/001968
Authority: WO
Inventors: 段荣书
Original assignee: 段颖哲
Priority date: 2010-03-17
Filing date: 2010-12-06
Publication date: 2011-09-22
Also published as: CN102188537B; CN102188537A

Abstract

A pharmaceutical composition for treating AIDS, preparation method, test method and use thereof, said pharmaceutical composition is prepared by the raw materials of Rhizoma Dioscoreae, Rhizoma Curculiginis, Fructus Lycii, Radix Rehmanniae, Radix rehmanniae Preparata preparatum, Herba Cistanches, Fructus Psoraleae, Radix Astragali, Fructus Corni, Herba Epimedii, Fructus Cnidii, Semen Myristicae, Cornu Cervi Pantotrichum etc.

Description

Pharmaceutical composition for treating AIDS and preparation method thereof

The invention relates to a traditional Chinese medicine composition, in particular to a traditional Chinese medicine composition for treating AIDS, belonging to the field of traditional Chinese medicine. Background technique

AIDS is a contagious disease that seriously threatens people's health. Its mortality rate is extremely high. At present, there is no effective vaccine prevention and no cure. It spreads widely and is popular, which not only causes huge economic losses, but also Seriously hindering social development has become a social issue of great concern to governments. As China's Ministry of Health, the State Planning Commission, the Ministry of Science and Technology, and the Ministry of Finance jointly formulated the "China Medium- and Long-Term Plan for Prevention and Control of AIDS" (1998-2010): "Prevention and control of AIDS is an urgent, complex and long-term arduous task. The task ", and believe that the current lack of effective AIDS, STD prevention and treatment experience and methods, most medical and health care institutions are still unable to provide standardized AIDS, STD treatment services." Proposed to accelerate the research on AIDS treatment drugs, strive to have a part The project reached the international advanced level in the same period, and some of the results were used for prevention and treatment. Therefore, exploring effective methods and drugs for the prevention and treatment of AIDS by Chinese medicine has important practical significance.

At present, there is no specific vaccine for the prevention and treatment of AIDS, and high-efficiency antiretroviral therapy (HAART) is currently the main method of AIDS treatment. Reasonable antiviral therapy has a certain effect on inhibiting HIV replication and improving patients' quality of life and survival. However, Western medicine antiviral treatment has the following problems: (1) It cannot completely eliminate HIV. Even if HIV is inhibited to an undetectable level in plasma for a long time, HIV is still replicating at a low level; (2) HIV resistance and drug resistance Adverse reactions: HAART can be up to 70% after 4 to 5 years of clinical application, and most patients have greater toxic side effects, resulting in decreased patient compliance, 25% of patients will stop HAART; (3) Limitations of indications: For HIV-infected patients with CD4+T cells >400/μ1 and plasma HIVRNA <30000, antiviral therapy is not advocated, while untreated patients have a >30% chance of developing AIDS within 3 years; (4) Expensive : Patients with HAART need about 800,000 yuan to 100,000 yuan per year. Currently, they can receive HAART patients at their own expense, with only 400 to 500 people per year. The vast majority of poor AIDS patients in China are in a state of no drug availability.

Because HAART treatment requires lifelong medication, for the purpose of shortening the medication time, the treatment is mostly initiated in the middle and late stages of infection. In fact, the immunodeficiency caused by HIV infection is a process of chronic progress of interaction between HIV virus and immune system. In the medium term, progressive destruction of immune tissues occurs. If the immune regulation can be treated in time to protect the infected person's immune system, it may delay the time of HAART treatment and play a good therapeutic role. Therefore, the search for safe and effective immune function, while anti-viral natural drugs have become an important research direction in the prevention and treatment of AIDS. Summary of the invention

SUMMARY OF THE INVENTION An object of the present invention is to provide a traditional Chinese medicine composition for treating AIDS, and to provide a preparation method of the traditional Chinese medicine composition and a method for detecting the active ingredient thereof. The object of the present invention is achieved by the following technical solutions.

plan 1 :

The traditional Chinese medicine composition for treating AIDS according to the present invention is prepared from the following raw materials by weight:

Deer antler 30~50 parts, Epimedium 120~160 parts, Astragalus 120~160. Parts, Cnidium 120~160 parts, Hawthorn

120~160 parts, Rehmannia glutinosa 240~330 parts.

The traditional Chinese medicine composition for treating AIDS according to the present invention is preferably made of the following raw materials by weight: 40 to 45 parts of velvet antler, 130 to 150 parts of Epimedium, 130 to 150 parts of Astragalus, 130 to 150 Cnidium 150 copies, Hawthorn

130~150 parts, Rehmannia glutinosa 260~300 parts.

The traditional Chinese medicine composition for treating AIDS according to the present invention is more preferably made of the following raw materials by weight: 42 parts of antler, 140 parts of Epimedium, 140 parts of Astragalus, 140 parts of Cnidium, 140 parts of Hawthorn, 280 parts of Rehmannia glutinosa.

Scenario 2:

30~50 parts of velvet antler, 120~160 parts of Epimedium, 120~160 parts of Astragalus, 120~160 parts of Cnidium, 120~160 parts of Hawthorn, 240~330 parts of Rehmannia glutinosa, 120~160 parts of C. chinensis, Nutmeg 120 ~160 servings, yam 120~160 servings.

130~150 parts, 260~300 parts of Rehmannia glutinosa, 130~150 parts of Curculigo, 130~150 parts of nutmeg, 130~150 parts of yam.

The traditional Chinese medicine composition for treating AIDS according to the present invention is more preferably made of the following raw materials by weight: 42 parts of antler, 140 parts of Epimedium, 140 parts of Astragalus, 140 parts of Cnidium, 140 parts of Hawthorn, 280 parts of Rehmannia glutinosa, 140 parts of Curculigo, 140 parts of nutmeg, 140 parts of yam.

Option 3:

30~50 parts of velvet antler, 120~160 parts of Epimedium, 120~160 parts of Astragalus, 120~160 parts of Cnidium, Hawthorn 120~160 parts, 240~330 parts of Rehmannia glutinosa, 120~160 parts of Curculigo, 120~160 parts of nutmeg, 120~160 parts of Chinese yam, 120~160 parts of medlar, 120~160 parts of Cistanche, 50~160 psyllium 85 copies.

130~150 parts of radix rehmannia 260~300 parts, curculigo 130~150 parts, nutmeg 130~150 parts, yam 130~150 parts, medlar 130~150 parts, Cistanche 130~150 parts, psoralen 65~75 Share.

The traditional Chinese medicine composition for treating AIDS according to the present invention is more preferably made of the following raw materials by weight: 42 parts of antler, 140 parts of Epimedium, 140 parts of Astragalus, 140 parts of Cnidium, 140 parts of Hawthorn, 280 parts of Rehmannia glutinosa, 140 parts of Curculigo, 1^ part of nutmeg, 140 parts of yam, 140 parts of medlar, 140 parts of Cistanche, and 70 parts of psoralen. The raw materials mentioned above are all Chinese herbal medicines or their processed products. The specific sources are:

Luhan: For the deer sika deer Cervus nippon Temminck or red deer Cervus elaphus Linnaeus stag The young horns of the ossified hairs.

Epimedium: Epimedium brevicornum Maxim., Epimedium sagittatum (Sieb. et Zucc.) Maxim. > Epimedium pubescens Maxim., Epimedium wushanense The dry ground part of TS Ying, or Epimedium koreanum Nakai.

Yellow: dried roots of Astragalus membranaceus (Fisch.) Bge. for the genus Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or membranaceus.

Cnidium: A dry mature fruit of the genus Cnidium monnieri (L.) Cuss.

Hawthorn: Dry ripe flesh of Cornus officinalis Sieb. et Zucc. Rehmannia glutinosa: A freshly processed or dried root of Rehmannia glutinosa Libosch., processed in accordance with the "wine stewing method" or "steaming method" in the Chinese medicine processing method.

Curculigo: The dried rhizome of the Amaryllidaceae Curculigo orchioides Gaertn.

Nutmeg: Dried kernels of the nutmeg Myristica fragrans Houtt., used after tanning. .

Yam: The dried roots of Dioscorea opposita Thunb.

Hazelnut: It is a dry ripe fruit of the Solanaceae plant Lycium barbarum L.

Cistanche: A dried, scaly fleshy stem of the Cistanche deserticola Y. C. Ma or Cistanche tubulosa (Schrenk) Wight.

Psoralen: A dry mature fruit of the leguminous psoralen Psoralea corylifolia L. The traditional Chinese medicine composition of each aspect of the present invention can be decoctioned by water after the traditional method, or can be processed according to the preparation, and suitable auxiliary materials are added to prepare various clinically required dosage forms, including tablets, granules and capsules. The agent, the pill, the oral liquid, the soft capsule, etc.; the auxiliary material includes a solvent, a disintegrant, a flavoring agent, a preservative, a coloring agent, a binder, a lubricant, and the like.

For oral solid dosage forms, the inventors provide a method of preparation comprising the steps of:

A. Take the above-mentioned raw materials, crush the velvet antler into fine powder, and set aside;

B. Distilling the nutmeg with water, collecting the volatile oil and encapsulating it with a sufficient amount of cyclodextrin, and the obtained clathrate is reserved; the distilled aqueous solution and the dregs are reserved for use;

C. Hawthorn, Curculigo, Cnidium, psoralen and 60%~90% ethanol are refluxed for 2~3 times, each time for 1~2 hours, combined with ethanol extract, ethanol is recovered, concentrated to 60° under reduced pressure. C, the relative density of 1. 25~1. 35 of the extract, extract and dregs spare;

D. Combine Rehmannia glutinosa, Epimedium, Astragalus, Cistanche, Gardenia, Yam and the slag obtained in steps B and C, add water to decoct 2~3 times, each time for 1~2 hours, combine water decoction and The extract of the extract in the step B, the relative density of 1. 25~1. 35, the standby;

E. Combine the extracts of steps C and D, vacuum dry, pulverize into dry paste powder, add velvet powder and beta-cyclodextrin inclusion compound of step B, and prepare the desired dosage form, including tablets, granules, Capsules, pills, soft capsules, etc.

Specifically, the inventors provide a method of preparing a tablet, the method comprising the steps of:

A. Take the raw material medicine, crush the velvet antler into fine powder, and set aside;

B. Distilling the nutmeg with 6 times the amount of water for 5 hours, collecting the volatile oil, and the obtained volatile oil is wrapped with 6 times the amount of betacyclodextrin, and the obtained clathrate is reserved; the distilled aqueous solution and the dregs are reserved for use;

C, the extract of hawthorn, curculigo, Cnidium, psoralen into a coarse powder, adding 80% ethanol reflux extraction 2 times, each time adding 5 to 6 times the amount, extracting 1. 5~2 hours, combined with ethanol extract, The ethanol is recovered, and the extract having a relative density of 1.30 is concentrated at 60 ° C under reduced pressure, and the extract and the dregs are reserved;

D. Decoction of Rehmannia glutinosa, Epimedium, Astragalus, Cistanche, Gardenia and Chinese yam twice, the first time with 10 times the amount of water for 2 hours, the second time with the steps B, C obtained dregs, 5的溶液, The high-temperature centrifugation, the centrifugation of the centrifugation solution is carried out by adding 8 times the amount of water to the boiling water for 1. 5 hours, and the aqueous solution obtained by the step B is concentrated to a concentration of 1. 05~1. , the extract having a relative density of about 1.30, which is further concentrated under reduced pressure to 60 Torr, is reserved;

E. Combine the extracts of steps C and D, vacuum dry, pulverize into dry paste powder, add antler powder, the beta-cyclodextrin inclusion compound of step B and the auxiliary materials required for preparation, and compress into tablets. The traditional Chinese medicine composition of the present invention contains various active ingredients, especially the content of icariin which affects the production The quality of the product. Therefore, in order to detect the content of each active ingredient in the traditional Chinese medicine composition, in particular, the content of icariin, the inventors have also provided a method for detecting an active ingredient, in addition to the conventional test items of pharmacy, The following qualitative identification and content determination methods are included.

Among them, the content determination method is:

Liquid chromatography conditions: using 18 垸垸 silicon germanium bonded silica as a filler; volume 28: 72 acetonitrile-water mixture as mobile phase; detection wavelength is 270nm _; theoretical plate number according to icariin peak should be calculated Not less than 1500;

Preparation of the reference solution: accurately weigh the icariin reference substance, add methanol to make a solution containing 0.1 mg per 1 ml, that is;

Preparation of the test solution: Take the traditional Chinese medicine composition 0. 3g~0. 5g, accurately weighed, placed in a conical flask, precision added 25ml of diluted ethanol, weighed, sonicated for 30 minutes, then weighed The weight of the lost weight is made up with dilute ethanol, shaken, filtered through a microporous membrane of 0. 45 μ πι, and the filtrate is taken, that is, obtained;

Assay: Accurately draw the reference solution and the test solution for each ΙΟ μ Ι , inject into the liquid chromatograph, measure and calculate the data.

The qualitative identification method includes the following items:

Α, take a small amount of traditional Chinese medicine composition, grind finely, and observe under the microscope, it can be seen that: the hair is broken and broken; the non-ossified bone tissue, nearly colorless, with most irregular block-like protrusions, with streaks visible in the gap;

• Β, take a small amount of traditional Chinese medicine composition, grind finely, add 30ml of ethanol, sonicate for 30 minutes, filter, and drain the filtrate on a water bath, add 1ml of methanol to dissolve the residue, as a test solution; take 5-hydroxyl Based on the furfural reference substance, add ethanol to make a solution containing 0.5 mg per lml, as a reference solution; according to the Chinese Pharmacopoeia thin layer chromatography test, take 5 μl of each of the above two solutions, respectively, on the same silica gel GF254 thin layer On the plate, a petroleum ether-ethyl acetate mixture with a volume ratio of 1:1 is used as a developing solvent, unrolled, taken out, dried, and placed under a UV light of 254 nm; in the chromatogram of the test product, corresponding to the chromatogram of the reference substance Position on the spot, showing the same color;

C. Take a small amount of traditional Chinese medicine composition, grind finely, add 30ml of ether, heat and reflux for 20 minutes, let cool, filter, the filtrate is evaporated, and the residue is added with 1ml of ethanol to dissolve, as the test solution; 5g, the same method to prepare the reference drug solution; according to the Chinese Pharmacopoeia thin-layer chromatography test, the above two solutions are taken 5 μ 1, each point on the same silica gel G thin-layer plate, the volume ratio is 20 : 5 : 8 : 0 2 of cyclohexanyl-dichloromethane-ethyl acetate-formic acid mixture as a developing solvent, unrolled, taken out, air-dried, sprayed with 10% sulfuric acid solution, and dried at 105 ° C until the spot color is clear; In the chromatogram, a spot of the same color is displayed at a position corresponding to the chromatogram of the reference drug;

D. Take a small amount of traditional Chinese medicine composition, grind finely, add 50ml of methanol, heat under reflux for 4 hours, filter, and evaporate the filtrate. Add 20 ml of water to the residue to dissolve, transfer to a separatory funnel, and saturate with water of 20ral, 15ral, 15ml respectively. The n-butanol is extracted once, and the n-butanol solution is combined, washed twice with ammonia test solution, 30 ml each time, and the ammonia test solution is discarded; n-butanol solution is saturated with n-butanol o

Wash the water 3 times, each time 30ml, discard the water; n-butanol solution is evaporated to dryness in a water bath, add 10ml of water to the residue to dissolve, let cool, pass D-101 macroporous adsorption resin column, wash with water 50ml Dissolve, discard the aqueous solution, elute with 30 ml of 40% ethanol, discard the eluate; elute with 50 ml of 70% ethanol, collect the eluate, evaporate to dryness, add 2 ml of methanol to the residue to dissolve. The test solution; another take astragaloside reference substance, add methanol to make lmg solution per lml, as a reference solution; according to the Chinese Pharmacopoeia thin layer chromatography test, draw the test solution Ιθμΐ, the reference solution 5μ1, respectively Point on the same silica gel G thin-layer plate, a mixture of dichloromethane-methanol-water in a volume ratio of 13:7:2 as a developing solvent, unroll, take out, dry, spray with 10% sulfuric acid ethanol solution, 105Ό Heating to the spot to clear the color; in the chromatogram of the test sample, in the position corresponding to the chromatogram of the reference substance, the spot of the same color is displayed under sunlight;

Ε, take the Cnidium medicinal herbs 0. 5g, add ether 30ml, heat reflux for 20 minutes, let cool, filter, the filtrate is evaporated, the residue is added with ethanol 1ml to dissolve, as a reference drug solution; according to Chinese Pharmacopoeia thin layer chromatography test 5 μl of each of the test solution and the Cnidium reference drug solution under C are dispensed on the same silica gel G thin layer plate, and the toluene-ethyl acetate mixture with a volume ratio of 30:1 is used as a developing solvent. , unfolding, taking out, drying, and setting it under 365nm ultraviolet light; in the chromatogram of the test sample, the spot of the same color is displayed at the position corresponding to the chromatogram of the reference drug;

F, take a small amount of traditional Chinese medicine composition, grind finely, add water 35ml, heat and boil for 15 minutes, let cool, filter, the filtrate is extracted twice with ethyl acetate, 15ml each time, steamed on a water bath, residue added with acetic acid 1ml of the ester is dissolved, as a test solution; another filbert reference drug 0. 5g, the same method to prepare a reference drug solution; according to the Chinese Pharmacopoeia thin layer chromatography test, draw the test solution, the negative sample solution each 10 μ ΐ 2 μ 1 of the reference drug solution was spotted on the same silica gel G thin layer plate, and the mixture of ethyl acetate-dichloromethane-formic acid in a volume ratio of 3:2:1 was used as a developing solvent, unrolled, taken out, and dried. , under the 365nm UV lamp; in the chromatogram of the test sample, the fluorescent spot of the same color is displayed at the position corresponding to the chromatogram of the reference drug;

G. Take a small amount of traditional Chinese medicine composition, and grind it. Extract the volatile oil according to the volatile oil method specified in the 2005 Chinese Pharmacopoeia. Add 1 ml of petroleum ether with a boiling range of 30~60'C from the upper end of the scale tube of the volatile oil extractor, and distill for 5 hours. Take petroleum ether solution as the test solution; take 2g of reference material of the nutmeg, and prepare the reference drug solution by the same method; according to the Chinese Pharmacopoeia thin layer chromatography test, draw the test solution and the reference drug solution 10 μ 1, respectively The same silica gel G thin-layer plate, with a volume ratio of 1:1 petroleum ether-toluene as a developing agent, unrolled, taken out, air-dried, sprayed with anisaldehyde test solution, heated at 105 ° C until the spot color is clear; In the chromatogram of the test sample, spots of the same color are displayed in daylight at a position corresponding to the chromatogram of the reference drug. The traditional Chinese medicine composition of each group of the invention has the effects of tonifying the kidney and strengthening the yang, and correcting the poisoning effect, and can be used for treating AIDS and improving various complications. It has been experimentally proved that the traditional Chinese medicine composition of the first embodiment of the present invention can effectively inhibit HIV, protect the immune system of experimental animals, and have an aphrodisiac effect on experimental animals; the traditional Chinese medicine composition of the second embodiment can further improve the constitution and appetite of the model animals. Reducing discomfort such as diarrhea; Chinese medicine combination #1 of Option 3 can comprehensively improve the therapeutic effect, replenish spleen and kidney, lead qi stagnation, and improve the quality of life of model animals and patients. The following animal experiment of the Chinese medicine composition of the scheme 3 and _The effect of the _η clinical test effect is exemplified, and the efficacy of each group of the traditional Chinese medicine composition of the present invention (named: Aifuping tablet in the experiment) is illustrated.

Experimental Example 1 : Experimental study of avidin tablets in the treatment of monkey immunodeficiency virus (SIV) infected monkey model

(1) Experimental drugs: Rehmannia glutinosa 28kg, velvet antler 4. 2kg, hawthorn 14kg, Epimedium 14kg, Astragalus 14kg, Cnidium 14kg, Curculigo 14kg, Cistanche 14kg, Scorpion 14kg, Nutmeg 14kg, Yam 14kg, Bone Lipid 7. Okg, made into tablets.

(II) Experimental methods: The monkey model was infected with SIVmac251, and the effect of Aifuping tablets against monkey immunodeficiency virus (SIV) was evaluated in vivo. Select healthy male rhesus monkeys (weight 3. 5~6. 5Kg) 12, infect SIVmac251 by intravenous injection

(5 doses of 100% monkey infection) Treatment was started 71 days after 1 ml, and were randomly divided into SIV control group, low dose group and high dose group, with 4 test monkeys in each group. The low-dose group is equivalent to the human clinical therapeutic amount, ie, 0. 338g/Kg; the high-dose group is equivalent to three times the low-dose group, ie, 1.014g/Kg, once a day, continuous administration for 8 weeks. , without interruption in the middle, continue to observe for 8 weeks after stopping the drug. Each was formulated into an aqueous suspension of 100 ml, and administered according to the actual body weight of the monkey. The SIV control group was an untreated group, and the same amount of warm boiled water was administered for 8 weeks.

(3) Experimental results:

1. Effects of Aifuping tablets on symptoms and signs of monkey model of monkey immunodeficiency virus (SIV) infection: During the experiment, the general condition of monkeys after SIV infection was good, the spirit was good, and the appetite was general. The changes in lymph node size before and after treatment in each group belonged to the usual response after infection with SIV, and there was no significant difference between the groups. One monkey in the SIV control group died 80 days after infection. The autopsy was seen: submandibular, axillary and inguinal lymph nodes; subcapsular lymph node enlargement, texture became solid; left and right lobes swollen, gray-red, texture became solid; colonic mucosa congestion, edema, focal erosion. The appetite, the spirit, etc. of other animals generally have no significant difference in body weight changes.

2. The inhibitory effect of Aifuping tablets on monkey immunodeficiency virus (SIV)-infected monkey model virus: The fluctuation of viral load in SIV control group after SIV infection is within a certain range, which is consistent with the natural variation of SIV infection. After the treatment in the low-dose group, the viral load decreased significantly, especially at 8 weeks after stopping the drug, and decreased by 1. 52 log compared with that before the treatment. 1. 34 log o Avoplanin high-dose group except one In addition to the accidental death of monkeys, the viral load of other monkeys also decreased significantly. The treatment group did not show a virus rebound after stopping the drug. Therefore, it can be considered that the experimental results suggest that Avovir tablets have a significant inhibitory effect on the SIV-infected monkey model.

3. The protective effect of Aifuping tablets on the immune system of monkey immunodeficiency virus (SIV) infected monkey model: The monkey lymph node biopsy showed that the lymph node structure of the control group gradually deteriorated with the prolongation of the disease course, which is consistent with the SIV infection model. The pathological changes of the natural pathology; the high-dose group in the treatment group was examined for lymph node examination, and its structure was slightly worse, but it was significantly better than the control group; the tissue structure of the low-dose group did not deteriorate with the disease course, but stabilized. The direction of development. It is suggested that Avopine has a certain protective effect on the immune system, and the low dose group is better than the high dose group.

Experimental Example 2: Experimental study of Aifuping tablets for tonifying kidney and strengthening yang _Q

(1) Experimental drugs: Ibid.

(B) Experimental methods: Hydrocortisone was used to induce yang deficiency syndrome in mice. After administration (0. 338g/Kg) for 4 days, body weight, body temperature, 10 minutes of autonomic activity and low temperature swimming survival time were measured. Castration of male rats into an animal model of kidney deficiency, administration

(0. 338 g/Kg) After 28 days, the penile erection time of the rats was recorded after local electrical stimulation. On the 29th day, the rats in each group were sacrificed. The foreskin gland, seminal vesicle, prostate and levator ani muscle were removed, weighed, and the organ index was calculated.

(III) Experimental results: Aifuping tablets can inhibit the decline of body weight of yang deficiency mice, significantly increase body temperature, significantly increase the number of spontaneous activities, prolong the survival time of low temperature swimming, and significantly shorten the penile erection latency of ovariectomized rats. It is suggested that Aifuping tablets have obvious functions of tonifying kidney and strengthening yang.

Experimental Example 3: Experimental study on the effect of Aifuping Tablet on immune function recovery in immunosuppressed mice

(1) Experimental drug: 1 The drug of the invention, as above, is made into a dry powder. 2 positive drugs: 贞芪 Fuzheng granules (national medicine Zhunzi Z22022497) Jilin Tonghua Shenyuan Pharmaceutical Co., Ltd. production. Cyclosporin A: Produced by Swiss Novartis Pharmaceuticals.

(2) Experimental methods:

1. Experimental animal group: Adult oral Avo Fu Ping dry powder 5. 8 g, is 0. 08319 g dry powder · kg - ¹ body weight. The equivalent dose of the mouse is 0. 754 g dry powder, kg- ¹ body weight. The equivalent dose of the mouse drug is used as the low dose; the equivalent dose is twice the medium dose; the equivalent dose is 4 times the high dose. Another set of normal animals, model animals and positive drug controls. The adult dose of positive drug is 30g per day, which is 0.43g · kg" ¹ body weight. The amount of mice is twice the equivalent dose, that is, 8 g dry powder * kg - ¹ body weight. Animals are randomly divided into groups of 12 animals.

2. Establishment of an animal model of immunosuppression: Animals were injected intraperitoneally with cyclosporin A (except for the normal control group) and injected once every other day for a total of 3 injections. The next day after the third injection, the administration was started by intragastric administration, 0.5 ml each time, once a day. Continuous administration for 2 weeks. The normal group and the model animal group were simultaneously administered with distilled water.

3. Lymphocyte subsets detection: bleeding in the eyelids of mice, anticoagulation of heparin. 0. lml take anticoagulant and _{_{CD: i, CD 4, CD}} 8 , and CD ₁₉ monoclonal antibody to a fluorescent binding 4Ό incubated for 30 minutes followed by lymphocyte subsets by flow cytometry.

(III) Experimental results: Compared with the model group, the CD ₃ ⁺ , CD T cell levels and CD ₄ ⁺ /CD ₈ + T cell ratios were significantly improved in the drug group. It is suggested that Aifuping tablets can promote the recovery of immune function.

Experimental Example 4: Toxicological study of Aifuping tablets

Because AIDS patients need to take medication for a long time, the safety of the drug itself is also crucial. The inventors conducted an animal acute poisoning test based on the guidelines of the Chinese medicine research guidelines.

(1) Acute toxicity test research data

The maximum concentration of Aifuping tablets was 2.46g crude drug/ml, and the mice were given 2 times/24h at the maximum concentration of maximum gavage volume (0.8 ml/20g). The cumulative dose was 197g/kg, which is equivalent to clinical adults. The dosage was 477 times (the clinical adult daily dose of 24.78g crude drug / 60 kg), the animal showed no obvious side effects, suggesting that the drug is safe and non-toxic in large doses. (2) Long-term toxicity test research data

With Aifuping tablets 24. 6g crude drug / kg · d, 12. 3g crude drug / kg · d, 6. 15g crude drug / kg · d three doses of continuous intragastric rats for 6 months, at this time, high, medium, The low dose is equivalent to 60.56, 29.78, 14.89 times of the 60kg adult weight. Results The administration period and the recovery observation period (one month) showed no significant difference in general condition, weight gain, main organ coefficient and macroscopic observation compared with the blank control group.

Hematological indicators: There was no significant difference in the majority of hematology indicators between the groups. The difference between the few doses of the different dose groups and the blank group was statistically significant, but it was basically within the normal range.

Blood biochemical indicators: There was no significant difference in the blood biochemical indicators of each group. A few different indicators also returned to normal after one month of restorative observation.

Microscopic histomorphological observation: rat heart, spleen, kidney, adrenal gland, brain, pituitary, trachea, thyroid, parathyroid gland, salivary gland, thymus, esophagus, large intestine, aorta, pancreas, ovary, uterus, testis, epididymis, There were no pathological changes in the prostate, bladder, breast, spinal cord, bone marrow (sternum, cervical vertebra), sciatic nerve, mesenteric lymph node and microscopic examination, while hepatocyte edema in a small part of the animal, interstitial inflammation in the lung, stomach and small intestine mucosa Inflammatory cell infiltration, after statistical treatment, there was no significant difference between the blank control group and the Aifuping tablets, indicating that Aifuping tablets had no obvious toxic effects.

Conclusion: Aifuping tablets are basically safe in the scope of clinical use.

Experimental Example 5: Clinical treatment of Aifuping tablets

From 1992 to 1993, the inventors used the traditional Chinese medicine compositions of the three sets of technical solutions of the present invention to treat AIDS in Kenya. A total of 239 patients were treated, all HIV-positive, with one or more opportunistic infections, 12 of whom had been treated with other anti-AIDS drugs, and 227 (94.9%) had no other treatment. Symptoms and signs have a higher incidence of fever, phlegm, diarrhea, itching, cough, loss of appetite, insomnia, loss of libido, and swollen lymph nodes. Take this medicine, 2~3 capsules/time, 2~3 times/day, take it after meals, and take it with boiled water. Even served 22 to 25 days, rest 6 to 7 days later. 83. 7% of the patients took the drug within 99 days, and only 14 patients (accounting for 5.9%) took more than 200 days. The total effective rate of treatment was 97.5%. Of the 14 patients who took the drug for more than 200 days, 3 patients had no viral load, accounting for 21. 4%. This result further demonstrates the therapeutic effect of the traditional Chinese medicine composition of the present invention on AIDS.

A number of experiments have shown that the traditional Chinese medicine compositions of the following groups of examples can achieve the effects of the above experimental examples to varying degrees, showing their therapeutic effects on AIDS and its complications, and the drug itself has no toxic side effects. DETAILED DESCRIPTION OF THE INVENTION - Example 1

Decoction 30g, Epimedium 120g, Astragalus 120g, Cnidium 120g, Hawthorn 120g, Rehmannia glutinosa 240g - boiled twice, add 10 times the amount of water each time. The decoction is taken orally and served on the same day for 6 months. Viral load is controlled to inhibit water _1Q level, the patient's self-inductive physical strength is significantly enhanced, and the quality of life is significantly improved.

Example 2:

500g of velvet antler, 1600g of Epimedium, 1600g of Astragalus, 1600g of Cnidium, 1600g of Hawthorn, and 3300g of Rehmannia glutinosa were boiled twice, and water was added 10 times each time. The decoction is sealed and packaged, kept at a constant temperature, and served in 10 days, for 5 months. The viral load was not detected, the patient's appetite was normal, the weight was normal, and the mental state was good.

Example 3:

Prescription: 50g of velvet antler, 160g of epimedium, 120g of astragalus, 160g of Cnidium, 120g of Hawthorn, 330g of Rehmannia glutinosa. Usage: Decoction the above raw materials together 2-3 times, add 8- 10 times of water each time, decoction orally, served at the time, for more than 3 months.

Effect: The prescription was applied to treat more than 30 cases of AIDS patients, with an effective rate of 92%.

Example 4:

Prescription: 40g of velvet, 130g of Epimedium, 130g of Astragalus, 130g of Cnidium, 130g of Hawthorn, 260g of Rehmannia glutinosa. Usage: Oral decoction.

Example 5

Prescription: Deer antler 45g, Epimedium 150g, Astragalus 150g, Cnidium 150g, Hawthorn 150g, Rehmannia glutinosa 300g. Usage: Oral decoction.

Example 6:

Prescription: Deer antler 45g, Epimedium 150g, Astragalus 150g, Cnidium 130g, Hawthorn 130g, Rehmannia 260g. Usage: Oral decoction.

Example 7

Prescription: antler 42g, epimedium 140g, astragalus 140g, Cnidium 140g, Hawthorn 140g, Rehmannia 280g. Usage: Oral decoction; or powdered antler, combined with water extract concentrate of other APIs, dried, crushed, and packed into capsules.

Effect: The side has been used to treat more than 70 cases of AIDS patients, with an effective rate of 96%.

Example 8

Prescription: antler 300g, epimedium 1200g, astragalus 1200g, Cnidium 1200g, Hawthorn 1200g, Rehmannia glutinosa 2400g, Curculigo 1200g, Nutmeg 1200g, Yam 1200g.

Process:

(1) taking the above-mentioned raw materials, crushing the velvet antler into fine powder, and waiting for it;

(2) heating the nutmeg with a sufficient amount of water to heat the steam, collecting the volatile oil produced and dissolving it with 70%, and storing it; the distilled aqueous solution and the dregs are set aside; _Χχ

(3) Add 2 times of 70% ethanol from Hawthorn, Curculigo, and Cnidium, and extract for 1 hour each time. Combine the ethanol extract, recover the ethanol, and concentrate to 60 ° C under reduced pressure. The relative density is 1.25~ 1.30 extract, extract and dregs for use;

(4) Combine rehmannia root, epimedium, astragalus, yam and the dregs obtained in step (2) (3), add enough water to cook twice, each time for 1 hour, combine water decoction and steps (2) The obtained aqueous solution is concentrated under reduced pressure to an extract having a relative density of 1.25 to 1.30 at 60 ° C, and used;

(5) Combine the extracts of steps (3) and (4), vacuum dry, pulverize into dry paste powder, add antler powder and appropriate amount of starch and dextrin, and granulate with the volatile oil ethanol solution in step (2). Dry and make granules.

Example 9

Prescription: 500g of velvet antler, 1600g of Epimedium, 1600g of Astragalus, 1600g of Cnidium, 1600g of Hawthorn, 3300g of Rehmannia glutinosa, 1600g of Curculigo, 1600g of nutmeg, 1600g of Chinese yam.

Process:

(1) Take the above-mentioned raw materials in proportion, and pulverize the velvet antler into fine powder for use;

(2) Distilling the nutmeg with 7 times the amount of water, collecting the volatile oil until no oil droplets are produced, adding the volatile oil to the 5-fold amount of betacyclodextrin, and drying the obtained clathrate; the aqueous solution and the drug after distillation The slag is reserved for use;

(3) The hawthorn, the curculigo, the cnidium and the 5 times amount of 90% ethanol were refluxed and extracted three times, each time for 2 hours, the ethanol extract was combined, the ethanol was recovered, and the relative density was 1.30~ when concentrated under reduced pressure to 60 °C. 1.35 extract, extract and dregs for use;

(4) Combine rehmannia root, epimedium, astragalus, yam and the dregs obtained in step (2) (3), add water to cook for 3 times, add 5 times of water each time, cook for 2 hours, combine with water to cook. The cooking liquid and the aqueous solution obtained in the step (2) are concentrated under reduced pressure to an extract having a relative density of 1.30 to 1.35 at 60 ° C, and used;

(5) Combining the extracts of steps (3) and (4), drying under reduced pressure, pulverizing into a dry paste powder, adding velvet powder and the beta-cyclodextrin inclusion compound of step (2), 1 time of starch , granulation, add a small amount of microcrystalline cellulose, mix and fill into capsules.

Example 10

Prescription: 300g of velvet antler, 1200g of epimedium, 1200g of Astragalus, 1200g of Cnidium, 1600g of Hawthorn, 3300g of Rehmannia glutinosa, 1600g of Curculigo, 1600g of nutmeg, 1200g of Chinese yam.

Process:

(1) Take the raw materials in proportion and pulverize the velvet antler into fine powder for use;

(2) The nutmeg, hawthorn, curculigo, and cnidium are pulverized into coarse powder, and refluxed with 80% ethanol for 2 times. The first time is added with 6 times for 2 hours, and the second time with 5 times for 1.5 hours. The ethanol extract is combined, the ethanol is recovered, and the extract having a relative density of 1.30 to 1.32 is concentrated to 6 CTC under reduced pressure, and the extract and the dregs are reserved; (3) Decoction of Rehmannia glutinosa, Epimedium, Astragalus and Chinese yam twice, the first time with 10 times the amount of water for 2 hours, the second time with the step (2) to obtain the dregs, add 8 times the amount Decoction for 1.5 hours, combined with water decoction, concentrated to 6CTC, the relative density of 1.05~1.10 clear paste, high-speed centrifugation, separate the centrate, continue to concentrate under reduced pressure to 6CTC, the relative density is about 1.30~1.32 Extract, spare;

(4) Combine the extracts of steps (2) and (3), vacuum dry, pulverize into dry paste powder, add antler powder, syrup, honey, etc., heat and mix to make a paste.

Example 11

Prescription: 400g of velvet antler, 1300g of epimedium, 1300g of Astragalus, 1300g of Cnidium, 1300g of Hawthorn, 2600g of Rehmannia glutinosa, 1300g of Curculigo, 1300g of nutmeg, 1300g of Chinese yam.

Process:

(2) Distilling the nutmeg with 8 times the amount of water for 6 hours, collecting the volatile oil, and wrapping it with 4 times the amount of cyclodextrin for 2 hours, and the obtained clathrate is dried and used; the distilled aqueous solution and the dregs are separately set. Standby

(3) Extracting hawthorn, curculigo, and Cnidium with 6 times 80% ethanol for 3 times, adding 8 times for the first time and extracting for 2 hours, extracting the second and third times with 5 times for 1 hour, combined with ethanol extraction. Liquid, recovered ethanol, concentrated under reduced pressure to 6CTC, the relative density of 1.26~1.28 extract, extract and dregs spare;

(4) Combine rehmannia root, epimedium, astragalus, yam and the dregs obtained in step (2) (3), add water for 3 times, and add 1 time 12 times water for 1.5 hours, 2, 3 Add 8 times the amount of water for 1 hour, combine the water decoction liquid and the aqueous solution obtained in step (2), and concentrate to a concentration of 1.26~1.28 of the extract at 60 减压 under reduced pressure, and set aside;

(5) Combining the extracts of steps (3) and (4), vacuum drying, pulverizing into dry paste powder, adding antler powder and the beta-cyclodextrin inclusion compound of step (2), appropriate amount of dextrin and crystallites Cellulose, mixed, pressed into tablets.

Example 12:

Prescription: antler 450g, epimedium 1500g, astragalus 1500g, Cnidium 1500g, Hawthorn 1500g, Rehmannia glutinosa 3000g, Curculigo 1500g, Nutmeg 1500g, Yam 1500g.

Process:

(2) Adding 5 times of water to the nutmeg for 4 hours, collecting the volatile oil, and wrapping it with 6 times the amount of cyclodextrin for 4 hours, and the obtained clathrate is reserved; the distilled aqueous solution and the dregs are reserved;

(3) Adding hawthorn, curculigo, and Cnidium to 8 times 70% ethanol for 2 times, each time for 1.5 hours, combining ethanol extract, recovering ethanol, and concentrating under reduced pressure to 60 ° C, the relative density is 1.30~ 1.32 extract, extract and dregs for use; (4) Decoction of Rehmannia glutinosa, Epimedium, Astragalus, and Yam twice, firstly add 10 times the amount of water for 1.5 hours, and the second time the dregs and the residue of step (2) (3) After the combination, add 6 times the amount of water to decoct for 1 hour, combine the water decoction liquid and the aqueous solution obtained in the step (2), and concentrate to a concentration of 1.30 to 1.32 at 6 CTC under reduced pressure, and set aside;

(5) Combining the extracts of steps (3) and (4), vacuum drying, pulverizing into a dry paste powder, adding velvet powder and the beta-cyclodextrin inclusion compound of step (2), 2 times the amount of starch, Add water to make soft materials and make pellets.

Example 13

Prescription: antler 450g, epimedium 1500g, astragalus 1500g, Cnidium 1500g, Hawthorn 1300g, Rehmannia glutinosa 2600g, Curculigo 1300g, nutmeg 1300g, Yam 1300g.

Process:

(2) Distilling the nutmeg with 4 times the amount of water, collecting the volatile oil until no oil droplets are produced, collecting the volatile oil, and waiting for use; - the distilled aqueous solution and the dregs are reserved for use;

(3) Extracting hawthorn, curculigo, and Cnidium with 5 times 90% ethanol for 3 times, extracting each time for 2 hours, combining ethanol extract, recovering ethanol, and concentrating to 60 Ό under reduced pressure at a relative density of 1.30~1.35. Extract, extract and dregs for use;

(5) Combine the extracts of steps (3) and (4), dry under reduced pressure, pulverize into dry paste powder, add 2.2 times vegetable oil and 0.1 times beeswax, heat and mix, then add antler powder and volatile oil, mix well Press into a soft capsule.

Example 14

Prescription: velvet 420g, epimedium 1400g, Astragalus 1400g, Cnidium 1400g, Hawthorn 1400g, Rehmannia glutinosa 2800g, Curculigo 1400g, Nutmeg 1400g, Yam 1400g.

Usage: Decoction the above raw material potion 2 times, add 8-10 times of water each time. The decoction is sealed and packaged, kept at a constant temperature, and served in 10 days, for 5 months.

Example 15

Prescription: 3kg of velvet antler, 12kg of Epimedium, 12kg of Astragalus, 12kg of Cnidium, 12kg of Hawthorn, 12kg of Radix Rehmanniae, 24kg of Rehmannia glutinosa, 12kg of Curculigo, 12kg of nutmeg, 12kg of yam, 12kg of medlar, 12kg of Cistanche, and 5.5kg of psoralen.

Usage: Decoction the above raw materials for 2 - 3 times, add 8-10 times each time. The decoction is sealed and packaged, and it is kept at a constant temperature. It is served in 10 days and used for 3 months.

Example 16: , ,

14

Prescription: 5kg of velvet antler, 16kg of Epimedium, 16kg of Astragalus, 16kg of Cnidium, 16kg of Hawthorn, 33kg of Rehmannia glutinosa, 16kg of C. chinensis, 16kg of nutmeg, 16kg of yam, 16kg of medlar, 16kg of Cistanche, and 8. 5kg of psoralen.

Process:

(2) heating and distilling the nutmeg with a sufficient amount of water, collecting the volatile oil produced and encapsulating it with a sufficient amount of beta-cyclodextrin, and drying the obtained clathrate; the aqueous solution and the dregs after distillation are separately set aside;

(3) Add 2 times of 60% ethanol of Hawthorn, Curculigo, Cnidium, and psoralen, extract 1 hour each time, combine ethanol extract, recover ethanol, and concentrate to 60Ό under reduced pressure. 1. 25~1. 30 extracts, extracts and dregs for use;

(4) Combine Rehmannia glutinosa, Epimedium, Astragalus, Cistanche, Gardenia, Yam and the dregs obtained in step (2) (3), add enough water to cook twice, each time for 1 hour, combined with water The immersion of the extract, and the relative density of the granules of 1. 25~1. 30, spare;

(5) Combining the extracts of steps (3) and (4), vacuum drying, pulverizing into a dry paste powder, adding velvet powder and the beta-cyclodextrin inclusion compound of step (2), and an appropriate amount of starch and paste. Fine, 60% ethanol dry pressed pellets, dried, made into granules.

Example 17

Prescription: 3kg of velvet antler, 12kg of Epimedium, 12kg of Astragalus, 12kg of Cnidium, 16kg of Hawthorn, 33kg of Rehmannia glutinosa, 16kg of C. chinensis, 16kg of nutmeg, 16kg of yam, 12kg of medlar, 12kg of Cistanche, and 5kg of psoralen.

Process:

(2) Distilling the nutmeg with 4 times the amount of water, collecting the volatile oil until no oil droplets are produced, adding the volatile oil to the 5-fold amount of betacyclodextrin, and drying the obtained clathrate; the aqueous solution and the drug after distillation The slag is reserved for use;

(3) Extracting hawthorn, curculigo, Cnidium, and psoralen with 5 times 90% ethanol for 3 times, extracting each time for 2 hours, combining ethanol extract, recovering ethanol, and concentrating to 60 减压 under reduced pressure. 1. 30~1. 35 extracts, extracts and dregs for use;

(4) Combine Rehmannia glutinosa, Epimedium, Astragalus, Cistanche, Gardenia, Yam and the dregs obtained in step (2) (3), add water for 3 times, add 5 times of water each time, and cook 2 times. The extract of the extract is used in an amount of 1. 30~1. 35 of the extract;

Effect: The side was used to treat more than 80 cases of AIDS patients, with an effective rate of 96.2%.

Example 18 The prescription: antler 4kg, epimedium 13kg, astragalus 13kg, Cnidium 13kg, hawthorn 13kg, rehmannia root 26kg, curculigo 13kg, nutmeg 13kg, yam 13kg, medlar 13kg, Cistanche 13kg, psoralen 6. 5kg.

Process -

(1) Take the raw materials in proportion, and pulverize the velvet antler into fine powder for use;

(3) Extract Hawthorn, Curculigo, Cnidium, and psoralen with 6 times 80% ethanol for 3 times, add 8 times for the first time for 2 hours, and add 2 times for the second and third times for 5 hours. , the extracts of the extracts, the extracts and the dregs of the extracts;

(4) Combine Rehmannia glutinosa, Epimedium, Astragalus, Cistanche, Gardenia, Yam and the dregs obtained in step (2) (3), add water for 3 times, and add 12 times the amount of water for the first time. 5的浸浸。 The immersed in the second and third times, the second and third times, the amount of water was decocted for 1 hour, the water was added to the water and the aqueous solution was condensed to a concentration of 1.26~1. Paste

(5) Combining the extracts of steps (3) and (4), vacuum drying, pulverizing into dry paste powder, adding antler powder and the beta-cyclodextrin inclusion compound of step (2), appropriate amount of dextrin and crystallite Cellulose, mixed, pressed into tablets.

Example 19

Prescription: antler 4. 5kg, epimedium 15kg, astragalus 15kg, Cnidium 15kg, hawthorn 15kg, rehmannia root 30kg, curculigo 15kg, nutmeg 15kg, yam 15kg, hazelnut 15kg, Cistanche 15kg, psoralen 7. 5g .

Process:

(1) Take the raw materials in proportion and pulverize the velvet antler into fine powder for use.

(2) Distilling the nutmeg with 5 times the amount of water for 4 hours, collecting the volatile oil, and wrapping it with 6 times the amount of cyclodextrin for 4 hours, and the obtained clathrate is reserved; the distilled aqueous solution and the dregs are reserved for use;

(3) Two times of extracting hawthorn, curculigo, Cnidium, and psoralen with 8 times 70% ethanol, extracting each time for 1.5 hours, combining ethanol extract, recovering ethanol, and concentrating to 60 ° under reduced pressure. C, the relative density of 1. 30~1. 32 of the extract, extract and dregs spare;

(4) Decoction of Rehmannia glutinosa, Epimedium, Astragalus, Cistanche, Gardenia, and Yam twice, the first time adding 10 times the amount of water to cook for 1. 5 hours, the second time the dregs and steps (2 5〜1. The relative density of the aqueous solution is 1. 30~1. The relative density of the aqueous solution is 1. 30~1. 32 extracts, spare;

(5) Combining the extracts of steps (3) and (4), vacuum drying, pulverizing into a dry paste powder, adding velvet powder and the beta-cyclodextrin inclusion compound of step (2), 2 times the amount of starch, Add water to make soft materials and make pellets. Lo

Example 20

Prescription: antler 4.5kg, epimedium 15kg, astragalus 13kg, Cnidium 13kg, hawthorn 15kg, rehmannia root 30kg, curculigo 15kg, nutmeg 15kg, yam 13kg, medlar 13kg, Cistanche 13kg, psoralen 6.5kg.

Process:

(2) Distilling the nutmeg with 6 times the amount of water for 5 hours, collecting the volatile oil, and the obtained volatile oil is wrapped with 6 times the amount of betacyclodextrin, and the obtained clathrate is reserved; the distilled aqueous solution and the dregs are reserved;

(3) The hawthorn, curculigo, cnidium, and psoralen are pulverized into coarse powder, and extracted with 80% ethanol under reflux for 2 times, the first time is added with 6 times for 2 hours, and the second time is added with 5 times for 1.5 hours. The ethanol extract is combined, the ethanol is recovered, and the extract is concentrated to a concentration of 1.30 to 1.32 at 60 ° C under reduced pressure, and the extract and the dregs are reserved;

(4) Decoction of Rehmannia glutinosa, Epimedium, Astragalus, Cistanche, Radix and Chinese yam twice, first time with 10 times water for 2 hours, second time with step (2) (3) Dilute the dregs, add 8 times the amount of water to decoct for 1.5 hours, combine the decoction liquid and the aqueous solution obtained in step (2), concentrate under reduced pressure to a clear density of 1.05~1.10 at 60C, centrifuge at high speed, and separate the centrifugation solution. And continue to concentrate under reduced pressure to 60 Ό when the relative density is about 1.30~1.32 of the extract, spare;

(5) Combining the extracts of steps (3) and (4), vacuum drying, pulverizing into dry paste powder, adding antler powder, the beta-cyclodextrin inclusion compound of step (2), syrup, honey, etc., heating Mix and make a paste.

Example 21 - Prescription: antler 4.2g, epimedium 14kg, astragalus 14kg, Cnidium 14kg, hawthorn 14kg, rehmannia root 28kg, curculigo 14kg, nutmeg 14kg, yam 14kg, wolfberry 14kg, Cistanche 14kg, psoralen 7kg.

Process:

(2) Distilling the nutmeg with 6 times the amount of water for 5 hours, collecting the volatile oil, and extracting the volatile oil with 4 times the amount of betacyclodextrin for 4 hours under TC conditions, and the resulting clathrate is used; after distillation The aqueous solution and the dregs are reserved for use;

(3) pulverize hawthorn, curculigo, cnidium and psoralen into coarse powder, add 2 times with 80% ethanol, add 6 times each time, extract for 1.5 hours, combine ethanol extract, recover ethanol, decompress The extract has a relative density of 1.28~ 1.30 when concentrated to 60 ° C, and the extract and the dregs are reserved;

(4) Decoction of Rehmannia glutinosa, Epimedium, Astragalus, Cistanche, Radix and Chinese yam twice, the first time with 12 times the amount of water for 1.5 hours, the second time and step (2) (3) Dilute the dregs, add 8 times the amount of water for 1 hour, combine the decoction liquid and the aqueous solution obtained in step (2), concentrate under reduced pressure to a clear density of 1.05~1.10 at 60 ° C, centrifuge at high speed, and separate. Centrifugal liquid, continue to concentrate under reduced pressure to 60 ° C, the relative density of about 1.28 ~ 1.30 of the extract, spare;

(5) Combine the extracts of steps (3) and (4), vacuum dry, pulverize into a thousand paste powder, add antler powder, microcrystalline fiber _Γη维素 and lactose amount, mix, granulate, dry, whole, add the _beta- cyclodextrin inclusion compound and a small amount of magnesium stearate in step (2), mix and compress to form tablets.

Effect: The side has been used to treat more than 200 cases of AIDS patients, with a total effective rate of 97%.

Example 22: Quality inspection of the tablets obtained in Example 21

[Qualitative identification]

(1) Take the product and study it carefully, and observe under the microscope: the hair is broken; the boneless tissue is not ossified, it is nearly colorless, and there are many irregular block-like protrusions, and streaks are faintly visible.

(2) Take 8 pieces of this product, remove the film coat, grind finely, add 30 ml of ethanol, sonicate for 30 minutes, filter, and evaporate the filtrate on a water bath. Add 1 ml of methanol to the residue to dissolve it, and use it as a test solution. 5重量的溶液。 As a reference solution, a solution of 5-hydroxymethylfurfural was added, and ethanol was added to make a solution containing 0.5 mg per 1 ml. According to the thin layer chromatography (Chinese Pharmacopoeia 2005 edition, an appendix IB) test, draw 5 μl of each of the above two solutions, respectively, on the same silica gel GF ₂₅₄ thin layer plate, with petroleum ether (60 ~ 90 ° C) - Ethyl acetate (1:1) is a spreading agent, unrolled, taken out, air-dried, and placed under a UV lamp (254 dishes). In the chromatogram of the test sample, spots of the same color are displayed at positions corresponding to the chromatogram of the reference substance.

(3) Take 8 pieces of this product, remove the film coat, grind finely, add ether 30ral, heat and reflux for 20 minutes, let cool, filter, the filtrate is evaporated, and the residue is added with ethanol lml to dissolve, as the test solution. Take the Hawthorn medicinal material 0. 5g, the same method to prepare the reference drug solution. According to the thin-layer chromatography (Chinese Pharmacopoeia 2005 edition, an appendix VI B) test, take 5 μl of each of the above two solutions, respectively, on the same silica gel G thin-layer plate, with cyclohexyl-dichloromethane-acetic acid Ethyl ester-formic acid (20:5:8:0.2) was used as a developing solvent, unrolled, taken out, air-dried, sprayed with 10% sulfuric acid solution, and dried at 105 Torr until the spots were clear. In the chromatogram of the test sample, spots of the same color are displayed at positions corresponding to the chromatogram of the reference drug.

(4) Take 14 pieces of this product, remove the film coat, grind finely, add 50ml of methanol, heat under reflux for 4 hours, filter, and evaporate the filtrate, add 20 ml of water to the residue to dissolve, transfer to the separatory funnel, and saturate with water. The butanol was extracted three times (20 ml, 15 ml, 15 ml), and the n-butanol solution was combined and washed twice with an ammonia test solution, 30 ml each time, and the ammonia test solution was discarded. The n-butanol solution was washed three times with saturated water of n-butanol, 30 ml each time, and the water was discarded. The n-butanol solution was evaporated to dryness on a water bath, and the residue was added with water 10 ml of warming to dissolve, and allowed to cool. The D-101 macroporous adsorption resin column (inner diameter: 1.5 cm, length 12 cm) was eluted with 50 ml of water, and water was discarded. The solution was eluted with 30 ml of 40% ethanol and the eluent was discarded. After eluting with 50 ml of 70% ethanol, the eluate was collected, evaporated to dryness, and the residue was dissolved in methanol (2 ml) to dissolve. Another reference substance of astragaloside IV was added, and methanol was added to make a solution containing 1 mg per lml as a reference solution. According to the thin-layer chromatography (Chinese Pharmacopoeia 2005 edition, an appendix VI B) test, draw the test solution Ιθμΐ, the reference solution 5μ1, respectively, on the same silica gel G thin-layer plate, with methylene chloride-methanol-water The lower layer solution of (13: 7: 2) is a developing solvent, unrolled, taken out, air-dried, sprayed with 10% sulfuric acid in ethanol, and heated at 105 ° C until the spots are clear. In the chromatogram of the test sample, spots of the same color are displayed in daylight at a position corresponding to the chromatogram of the reference substance.

(5) Take the Cnidium chinensis reference material 0. 5g, add ether 30ml, heat reflux for 20 minutes, let cool, filter, the filtrate is dried, _{1 Q} residue was added with 1 ml of ethanol to dissolve, and used as a reference drug solution. According to the thin-layer chromatography (Chinese Pharmacopoeia 2005 edition, an appendix VIB) test, the 5 μ 1 of the test solution and the Cnidium reference drug solution under the identification (3) are respectively placed on the same silica gel G thin layer plate. , using toluene-ethyl acetate (30:1) as a developing solvent, unrolling, taking out, drying, and viewing under ultraviolet light (365 nm). In the chromatogram of the test sample, spots of the same color are displayed at positions corresponding to the chromatogram of the reference drug.

(6) Take 8 pieces of this product, remove the film coat, grind finely, add 35ml of water, boil for 15 minutes, let cool, filter, and extract the filtrate twice with ethyl acetate, 15ml each time, steam on the water bath. The residue was added with 1 ml of ethyl acetate to dissolve, and used as a test solution. Another scorpion reference drug 0. 5g, the same method to prepare a reference drug solution. According to the thin layer chromatography (Chinese Pharmacopoeia 2005 edition of an Appendix VI B) test, draw the test solution, the negative sample solution 10 μl, the reference drug solution 2 μ 1, respectively, on the same silica gel G thin-layer plate, Ethyl acetate-dichloromethane-formic acid (3:2:1) was used as a developing solvent, developed, taken out, dried, and placed under UV light (365 nm). In the chromatogram of the test sample, fluorescent spots of the same color are displayed at positions corresponding to the chromatogram of the reference drug.

(7) Take 20 pieces of this product, remove the film coat, and grind the fine oil. According to the volatile oil determination method (Chinese Pharmacopoeia 2005 edition, an appendix KD), extract the volatile oil, and add petroleum ether (30~60 °C) from the upper end of the volatile oil extractor scale tube. Lml, distilled for 5 hours, and the petroleum ether solution was taken as the test solution. Another 2 g of the reference material of the nutmeg was prepared, and the reference medicine solution was prepared by the same method. According to the thin-layer chromatography (Chinese Pharmacopoeia 2005 edition, an appendix VI B) test, draw the test solution and the reference drug solution 10 μ 1, respectively, on the same silica gel G thin-layer plate, with petroleum ether (60~90°) C) - Toluene (1: 1) is a developing agent, spread, removed, dried, sprayed with anisaldehyde test solution, heated at 105 ° C until the spots are clear. In the chromatogram of the test sample, spots of the same color are displayed in daylight at a position corresponding to the chromatogram of the reference drug.

[Content determination]

Chromatographic conditions and system suitability test: octadecyl silicon germanium bonded silica as a filler; acetonitrile-water (28: 72) as mobile phase; detection wavelength is 270 dishes. The number of theoretical plates should be no less than 1500 according to the peak of icariin.

Preparation of the reference solution: Accurately weigh the appropriate amount of icariin reference substance, add methanol to make a solution containing 0.1 mg per lml, that is.

Preparation of the test solution: Take 20 pieces of this product, remove the film coat, grind finely, take about 0. 5g, accurately weighed, set in a conical flask, precision added 25ml of dilute ethanol, weighed, sonicated (power: 240W, frequency: 45kHz) 30 minutes, weigh the weight, make up the lost weight with dilute ethanol, shake well, filter with microporous membrane (0. 45 μ πι), take the filtrate, get .

Assay: Accurately draw 10 μl of each of the reference solution and the test solution into the liquid chromatograph and measure. Results: The product at each containing Epimedium icariin (C _M .0 ₁₅₎ not less than 0. 50mg.

Claims

Rights request

A traditional Chinese medicine composition for treating AIDS, characterized in that the active ingredient of the traditional Chinese medicine composition is made of the following raw materials by weight:

Deer antler 30~50 parts, Epimedium 120~160 parts, Astragalus 120~160 parts, Cnidium 120~160 parts, Hawthorn 120~160 parts, Rehmannia glutinosa 240~330 parts.

2. The traditional Chinese medicine composition according to claim 1, wherein the composition of each of the raw materials is:

40~45 parts of velvet antler, 130~150 parts of Epimedium, 130~150 parts of Astragalus, 130~150 parts of Cnidium, 130~150 parts of Hawthorn, 260~300 parts of Rehmannia glutinosa.

3. The traditional Chinese medicine composition according to claim 2, wherein the composition of each of the raw materials is:

42 velvet antler, 140 epimedium, 140 radix, 140 cnidium, 140 hawthorn, and 280 rehmannia.

4. A traditional Chinese medicine composition for treating AIDS, characterized in that the active ingredient of the traditional Chinese medicine composition is made of the following raw materials by weight:

30~50 parts of velvet antler, 120~160 parts of Epimedium, 120~160 parts of Astragalus, 120~160 parts of Cnidium, 120~160 parts of Hawthorn, 240~330 parts of Rehmannia glutinosa, 120~160 parts of C. chinensis, Nutmeg 120 ~160 servings, 120 to 160 copies of yam.

The traditional Chinese medicine composition according to claim 4, wherein the composition of each of the raw materials is - 40 to 45 parts of velvet, 130 to 150 parts of Epimedium, 130 to 150 parts of Astragalus, 130 to 150 parts of Cnidium, Hawthorn 130~150 parts, Rehmannia 260~300 parts, Curculigo 130~150 parts, Nutmeg 130~150 parts, Yam 130~150 parts. '

6. The traditional Chinese medicine composition according to claim 5, wherein the composition of each of the raw materials is:

42 velvet antler, 140 epimedium, 140 radix, 140 cnidium, 140 hawthorn, 280 rehmannia, 140 condiment, 140 nutmeg, and 140 yam.

7. A traditional Chinese medicine composition for treating AIDS, characterized in that the active ingredient of the traditional Chinese medicine composition is made of the following raw materials by weight:

30~50 parts of velvet antler, 120~160 parts of Epimedium, 120~160 parts of Astragalus, 120~160 parts of Cnidium, 120~160 parts of Hawthorn, 240~330 parts of Rehmannia glutinosa, 120~160 parts of C. chinensis, Nutmeg 120 ~160 parts, 120~160 parts of yam, 120~160 parts of medlar, 120~160 parts of Cistanche, and 55~85 parts of psoralen.

8. The traditional Chinese medicine composition according to claim 7, wherein the composition of each of the drug substances is:

40~45 parts of velvet antler, 130~150 parts of Epimedium, 130~150 parts of Astragalus, 130~150 parts of Cnidium, 130~150 parts of Hawthorn, 260~300 parts of Rehmannia glutinosa, 130~150 parts of C. chinensis, Nutmeg 130 ~150 parts, 130~150 parts of yam, 130~150 parts of medlar, 130~150 parts of Cistanche, and 65~75 parts of psoralen.

9. The traditional Chinese medicine composition according to claim 8, wherein the ratio of each raw material medicine is:

42 antler, 140 yam, 140 radix, 140 cnidium, 140 hawthorn, 280 rehmannia, 140 cichlids, 140 nutmeg, 140 yam, 140 hazelnuts, meat scent 140 parts, 70 parts of psoralen.

The method of preparing a traditional Chinese medicine composition according to any one of claims 7 to 9, characterized in that the method comprises the following process steps:

C. Hawthorn, Curculigo, Cnidium, psoralen and 60%~90% ethanol are refluxed for 2~3 times, each time for 1~2 hours, combined with ethanol extract, ethanol is recovered, and concentrated under reduced pressure to 60 Ό. The extract having a density of 1. 25~1. 35, the extract and the dregs are reserved;

E. Combine the extracts of steps C and D, vacuum dry, pulverize into dry paste powder, add velvet powder and the beta-cyclodextrin inclusion compound of step B to prepare the desired dosage form.

11. The method of preparing a traditional Chinese medicine composition according to claim 10, characterized in that the method comprises the following process steps:

D. Decoction of Rehmannia glutinosa, Epimedium, Astragalus, Cistanche, Gardenia and Chinese yam twice, the first time with 10 times the amount of water for 2 hours, the second time with the steps B, C obtained dregs, 5的清膏, high-speed centrifugation, fractionation, with a water-repellent solution, and a solution of the aqueous solution of the step B, and concentrated to a concentration of 1. 05~1. The extract is further concentrated under reduced pressure to 60 ° C, and the relative density is about 1.30.

E. Combine the extracts of steps C and D, vacuum dry, pulverize into dry paste powder, add antler powder, the beta-cyclodextrin inclusion compound of step B and the auxiliary materials required for preparation, and compress into tablets.

The method for detecting an active ingredient of a traditional Chinese medicine composition according to any one of claims 7 to 9, which comprises qualitative identification and content determination, wherein the content determination method is: Liquid chromatography conditions: octadecylsilicone bonded silica gel as a filler; acetonitrile-water mixture with a volume ratio of 28:72 as mobile phase; detection wavelength of 270 dishes; theoretical plate number according to icariin peak The calculation should be no less than 1500;

Assay: Accurately draw 10 μl of each of the reference solution and the test solution into the liquid chromatograph, measure and calculate the data.

The method for detecting an active ingredient of a traditional Chinese medicine composition according to claim 12, wherein the qualitative identification method comprises the following contents:

Β, take a small amount of traditional Chinese medicine composition, grind finely, add 30ml of ethanol, sonicate for 30 minutes, filter, leave the filtrate on the K bath and evaporate dry, add 1ml of methanol to dissolve the residue, as a test solution; take 5-hydroxyl Based on the furfural reference substance, add ethanol to make a solution containing 0.5 mg per lml, as a reference solution; according to the Chinese Pharmacopoeia thin layer chromatography test, take 5 μl of each of the above two solutions, respectively, on the same silica gel GF254 thin layer On the plate, a petroleum ether-ethyl acetate mixture with a volume ratio of 1:1 is used as a developing solvent, unrolled, taken out, dried, and placed under a UV light of 254 nm; in the chromatogram of the test product, corresponding to the chromatogram of the reference substance On the position, the spots of the same color;

C. Take a small amount of traditional Chinese medicine composition, grind finely, add 30ml of ether, heat and reflux for 20 minutes, let cool, filter, the filtrate is evaporated, and the residue is added with 1ml of ethanol to dissolve, as the test solution; 5g, the same method to prepare the reference drug solution; according to the Chinese Pharmacopoeia thin-layer chromatography test, the above two solutions are taken 5 μ 1, each point on the same silica gel G thin-layer plate, the volume ratio is 20 : 5 : 8 : 0 2 cyclohexane-dichloroformamidine-ethyl acetate-formic acid mixture is used as a developing solvent, unrolled, taken out, air-dried, sprayed with 10% sulfuric acid solution, and dried at 105 ° C until the spot color is clear; In the chromatogram of the product, a spot of the same color is displayed at a position corresponding to the chromatogram of the reference drug;

D. Take a small amount of traditional Chinese medicine composition, grind finely, add 50ml of methanol, heat under reflux for 4 hours, filter, and evaporate the filtrate. Add 20 ml of water to the residue to dissolve. Transfer to a separatory funnel and saturate with 20 ml, 15 ml, 15 ml of water respectively. The n-butanol was extracted once, and the n-butanol solution was combined, washed twice with ammonia test solution, 30 ml each time, and the ammonia test solution was discarded; n-butanol solution was washed 3 times with water saturated with n-butanol, 30 ml each time. , discard the water solution; n-butanol solution is evaporated to dryness in a water bath, the residue is added with water lOral warm to dissolve, let cool, pass the D-101 macroporous adsorption resin column, elute with 50ml of water, discard the water, and then use 30 ml of 40% ethanol was eluted, and the eluate was discarded. After elution with 50 ml of 70% ethanol, the eluate was collected, evaporated to dryness, and the residue was dissolved in methanol (2 ml) to dissolve. For the test solution; take the astragaloside reference substance, add methanol to make lrag solution per lml, as a reference solution; according to the Chinese Pharmacopoeia thin layer chromatography test, draw the test solution Ιθμΐ, the reference solution 5μ1, Place on the same silica gel G thin-layer plate, and use a mixture of dichloromethane-methanol-water in a volume ratio of 13:7:2 as a developing solvent, unroll, take out, dry, and spray with 10% sulfuric acid ethanol solution. , heating at 105 ° C until the spots are clear; in the chromatogram of the test sample, the spots of the same color are displayed in the sunlight at the position corresponding to the chromatogram of the reference substance;

Ε, take the Cnidium medicinal material 0. 5g, add ether 30ml, heat reflux for 20 minutes, let cool, filter, the filtrate is evaporated, the residue is added with ethanol 1ml to dissolve, as a reference drug solution; according to Chinese Pharmacopoeia thin layer chromatography test 5 μl of each of the test solution and the Cnidium reference drug solution under C are dispensed on the same silica gel G thin layer plate, and the toluene-ethyl acetate mixture with a volume ratio of 30:1 is used as a developing solvent. , unfold, remove, dry, and set under the 365mn ultraviolet light; in the chromatogram of the test sample, the spot of the same color is displayed at the position corresponding to the chromatogram of the reference drug;

F, take a small amount of traditional Chinese medicine composition, grind finely, add water 35ml, heat and boil for 15 minutes, let cool, filter, the filtrate is extracted twice with ethyl acetate, 15ml each time, steamed on a water bath, residue added with acetic acid The ester lml is dissolved, as a test solution; another scorpion reference drug 0. 5g, the same method to prepare a reference drug solution; according to the Chinese Pharmacopoeia thin layer chromatography test, the test solution, the negative sample solution each 10 μ 1 2 μ 1 of the reference drug solution was spotted on the same silica gel G thin layer plate, and the mixture of ethyl acetate-dichloromethane-formic acid in a volume ratio of 3:2:1 was used as a developing solvent, unrolled, taken out, and dried. , set the 365 dish under the UV lamp; in the chromatogram of the test sample, the fluorescent spot of the same color is displayed at the position corresponding to the chromatogram of the reference drug;

G. Take a small amount of traditional Chinese medicine composition, and grind it. Extract the volatile oil according to the volatile oil method specified in the 2005 Chinese Pharmacopoeia. Add 1 ml of petroleum ether with a boiling range of 30~60 °C from the upper end of the scale tube of the volatile oil extractor, and distill for 5 hours. Take petroleum ether liquid as the test solution; take 2g of reference material of the nutmeg, and prepare the reference medicine solution by the same method; according to the Chinese Pharmacopoeia thin layer chromatography test, draw the test solution and the reference drug solution 10 μ 1 , respectively On the same silica gel G thin-layer plate, with a volume ratio of 1:1 petroleum ether-toluene as a developing agent, spread, take out, dry, spray with anisaldehyde test solution, and heat at 105 ° C until the spots are clear; In the chromatogram of the test sample, spots of the same color are displayed in daylight at a position corresponding to the chromatogram of the reference drug.

14. Use of a traditional Chinese medicine composition according to any one of claims 1 to 9 for the preparation of a medicament for the treatment of AIDS.

15. Use of a traditional Chinese medicine composition according to any one of claims 1 to 9 for the preparation of a medicament for warming kidney yang.