Composition for treatment of asthma

Abstract

The present invention discloses a pharmaceutical preparation of Chinese herbal medicines which consists of Chinese herbal medicines for tonifying kidney and antiasthma, wherein the Chinese herbal medicines are Perilla Frutescens, Prunus Armeniaca, Glycyrrhiza Uralensis, Scutellaria Baicalensis, Coptis Chinesis, Tusilago Farfara, Stemona Sessilifolia, Fritllaria Cirrhosa, Pheretima Aspergillum, Psoralea Corylifolia, Codonopsis Pilosula, Hordeum Vulgara, Massa Fermentata Medicalis, Schisandra Chinensis, Gypsum. The preparation has been used in China for 20 years, and in Israel for more than 5 years. It has been used to treat thousands of patients suffering from asthma with an effective rate of 93%. The present preparation can relieve cough, expel phlegm, resist airway allergic inflammation reaction, improve pulmonary function, partial pressure of the oxygen in blood and increase CD2, CD4, CD4/CD8, reduce IgE in blood, and increase CAMP, reduce CGMP, stabilize mast cells, inhibit the release of histamine, which makes it capable of stopping the attack of asthma. As shown with an electron microscope, the preparation protects lung cells, increases lung cells of type 2, and recovers the lung's capacity. It can be applied to the hormone dependent patients for decreasing and ceasing the administration of hormone by adjusting hypothalamic-pituitary-adrenal axis. To further demonstrate the therapeutic effect, a clinical trial carried in the Tel-Hashomer Hospital of Israel proved the preparation can improve asthma significantly.

Description

FIELD OF THE INVENTION

[0001] This application is §371 of PCT/CN01/01522, filed Nov. 1, 2001. The present invention relates to a composition for the treatment of asthma. More particularly, the present invention relates to a composition for treating asthma made from Chinese herbal medicine.

BACKGROUND OF THE INVENTION

[0002] Several studies have indicated that the prevalence rate of asthma is increasing in many regions while the morbidity rate remains high. Despite progress in the research concerning pathogenesis mechanism and therapy for asthma, morbidity rate and even mortality rate of this disease in the advanced countries is increasing. At present, the preventive therapy for asthma is mainly based on systemic corticosteroids administrated by inhalation and oral route. But significant adverse effects were found with long-term use of hormone. Therefore patients often express interest in exploiting non-Western Medicine approaches to prevent and relieve the symptoms of asthma. In China, herbal therapy has been used for several centuries as therapy for asthma with significantly beneficial effects, since the composition of herbs is not standardized and is individualized for each patient by adding or reducing the components therein. The previous formulas were used to treat asthma only for one side, for example only for asthma attacks or for prevention.

CONTENT OF THE INVENTION

[0003] Based on long term research, the inventor finds the following prescriptions (PCCJ) are useful in the attack period and catabasis of asthma. The compositions are made of both medicines for anti-asthma attack and those for preventing asthma (combination of herbal medicines for tonifying kidney and those for eliminating pathogenic factors), and specially are made from a part or all of the following Chinese herbal medicine: Ma Huang (EPHEDRA SINICA), Xing Ren (PRUNUS ARMENIACA), Gan Cao (GLYCYRRHIZA URALENSIS), Huang Qin (SCUTELLARIA BAICALENSIS), Huang Lian (COPTIS CHINESIS), Huang Bai (PHELLODENDRON CHINENSE), Kuan Dong Hua (TUSILAGO FARFARA), Bai Bu (STEMONA SESSILIFOLIA), Chuan Bei Mu (or Bei Mu) (FRITLLARIA CIRRHOSA), Di Long (PHERETIMA ASPERGILLUM), BU Gu Zhi (PSORALEA CORYLIFOLIA), Dang Shen (CODONOPSIS PILOSULA), Shan Zha (CRATAEGRUS PINNATIFIDA), Mai Ya (HORDEUM VULGARA), Shen Qu (MASSA FERMENTATA MEDICALIS), Wu Wei Zi (SCHISANDRA CHINENSIS), Shi Gao (GYPSUM), Su Zi (FERILLA FRUTESCENS), Zi Wan (ASTER TATARICUS), Bai Shao (PAEONIA LACTIFLORA), Jin Yin Hua (LONICERA JAPONICA), Lian Qiao (FORSYTHIA SUSPENSA), Jing Jie (SCHIZONEPETA TENUIFOLIA), Huang Qi (ASTRAGALUS MEMBRANACEUS), Fang Feng (LEDEBOURIELLA DIVARICATA).

[0004] From the above list of Chinese herbal medicines, the following 7 specific prescriptions are preferable, in which Prescription 1 is the basic one (research formula) and Prescriptions 2 to 6 are adding or reducing ones.

	PRESCRIPTION 1
	% amount
Name (pinyin)	Latin Name (species)	(w/w)
MA HUANG	EPHEDRA SINICA	5.1%
XING REN	PRUNUS ARMENIACA	6.12%
GAN CAO	GLYCYRRHIZA URALENSIS	5.1%
HUANG QIN	SCUTELLARIA BAICALENSIS	6.12%
HUANG LIAN	COPTIS CHINESIS	6.12%
HUANG BAI	PHELLODENDRON CHINENSE	6.12%
KUANG DONG	TUSILAGO FARFARA	5.1%
HUA
BAI BU	STEMONA SESSILIFOLIA	5.1%
CHUAN BEI MU	FRITLLARIA CIRRHOSA	5.1%
DI LONG	PHERETIMA ASPERGILLUM	5.1%
BU GU ZHI	PSORALEA CORYLIFOLIA	5.1%
DANG SHEN	CODONOPSIS PILOSULA	6.12%
SHAN ZHA	CRATAEGRUS PINNATIFIDA	4.1%
MAI YA	HORDEUM VULGARA	2.04%
SHEN QU	MASSA FERMENTATA MEDICALIS	2.04%
WU WEI ZI	SCHISANDRA CHINENSIS	5.1%
SHI GAO	GYPSUM	15.31%
SU ZI	PERILLA FRUTESCENS	5.1%

[0005]

	PRESCRIPTION 2
	% amount
Name (pinyin)	Latin Name (species)	(w/w)
MA HUANG	EPHEDRA SINICA	5.1(1-10)%
XING REN	PRUNUS ARMENIACA	6.12(1-10)%
GAN CAO	GLYCYRRHIZA URALENSIS	5.1(1-10)%
HUANG QIN	SCUTELLARIA BAICALENSIS	6.12(1-10)%
HUANG LIAN	COPTIS CHINESIS	6.12(1-15)%
HUANG BAI	PHELLODENRON CHINENSE	6.12(1-15)%
KUANG DONG HUA	TUSILAGO FARFARA	5.1(1-10)%
BAI BU	STEMONA SESSILIFOLIA	5.1(1-10)%
CHUAN BEI MU	FRITLLARIA CIRRHOSA	5.1(1-10)%
DI LONG	PHERETIMA ASPERGILLUM	5.1(1-15)%
BU GU ZHI	PSORALEA CORYLIFOLIA	5.1(1-10)%
DANG SHEN	CODONOPSIS PILOSULA	6.12(1-10)%
SHAN ZHA	CRATAEGRUS PINNATIFIDA	4.1(1-8)%
MAI YA	HORDEUM VULGARA	2.04(1-6)%
SHEN QU	MASSA FERMENTATA MEDICALIS	2.04(1-6)%
WU WEI ZI	SCHISANDRA CHINENSIS	5.1(1-10)%
SHI GAO	GYPSUM	15.31(5-30)%
SU ZI	PERILLA FRUTESCENS	5.1(1-10)%

[0006]

	PRESCRIPTION 3
	% amount
Name (pinyin)	Latin Name (species)	(w/w)
MA HUANG	EPHEDRA SINICA	5.1(1-30)%
XING REN	PRUNUS ARMENIACA	6.12(1-30)%
GAN CAO	GLYCYRRHIZA URALENSIS	5.1(1-30)%
HUANG QIN	SCUTELLARIA BAICALENSIS	6.12(1-35)%
HUANG LIAN	COPTIS CHINESIS	6.12(1-35)%
HUANG BAI	PHELLODENRON CHINENSE	6.12(1-35)%
KUANG DONG HUA	TUSILAGO FARFARA	5.1(1-30)%
BAI BU	STEMONA SESSILIFOLIA	5.1(1-30)%
CHUAN BEI MU	FRITLLARIA CIRRHOSA	5.1(1-30)%
DI LONG	PHERETIMA ASPERGILLUM	5.1(1-35)%
BU GU ZHI	PSORALEA CORYLIFOLIA	5.1(1-30)%
DANG SHEN	CODONOPSIS PILOSULA	6.12(1-30)%
SHAN ZHA	CRATAEGRUS PINNATIFIDA	4.1(1-30)%
MAI YA	HORDEUM VULGARA	2.04(1-30)%
SHEN QU	MASSA FERMENTATA MEDICALIS	2.04(1-30)%
WU WEI ZI	SCHISANDRA CHINENSIS	5.1(1-30)%
SHI GAO	GYPSUM	15.31(5-50)%
SU ZI	PERILLA FRUTESCENS	5.1(1-30)%

[0007]

	PRESCRIPTION 4
	% amount
Name (pinyin)	Latin Name (species)	(w/w)
XING REN	PRUNUS ARMENIACA	6.12(1-30)%
GAN CAO	GLYCYRRHIZA URALENSIS	6(1-30)%
HUANG QIN	SCUTELLARIA BAICALENSIS	6.12(1-35)%
HUANG LIAN	COPTIS CHINESIS	6.12(1-35)%
ZI WAN	ASTER TATARICUS	5.1(1-30)%
BAI BU	STEMONA SESSILIFOLIA	5.1(1-30)%
BEI MU	FRITLLARIA CIRRHOSA	5.1(1-30)%
DI LONG	PHERETIMA ASPERGILLUM	5.1(1-35)%
BU GU ZHI	PSORALEA CORYLIFOLIA	5.1(1-30)%
DANG SHEN	CODONOPSIS PILOSULA	6.12(1-30)%
SHAN ZHA	CRATAEGRUS PINNATIFIDA	4.1(1-30)%
MAI YA	HORDEUM VULGARA	2.04(1-30)%
SHEN QU	MASSA FERMENTATA MEDICALIS	2.04(1-30)%
WU WEI ZI	SCHISANDRA CHINENSIS	5.1(1-30)%
SHI GAO	GYPSUM	15.31(1-50)%
SU ZI	PERILLA FRUTESCENS	5.1(1-30)%

[0008] In the prescription, BAI SHAO (PAEONIA LACTIFLORA) can be added in the amount of 4(1-30)%.

	PRESCRIPTION 5
	% amount
Name (pinyin)	Latin Name (species)	(w/w)
XING REN	PRUNUS ARMENIACA	6.12(1-30)%
GAN CAO	ASTER TATARICUS	6(1-30)%
HUANG QIN	SCUTELLARIA BAICALENSIS	6.12(1-35)%
HUANG LIAN	COPTIS CHINESIS	6.12(1-35)%
HUANG BAI	PHELLODENRON CHINENSE	6.12(1-35)%
KUANG DONG HUA	TUSILAGO FARFARA	5.1(1-30)%
BAI BU	STEMONA SESSILIFOLIA	5.1(1-30)%
BEI MU	FRITLLARIA CIRRHOSA	5.1(1-30)%
DI LONG	PHERETIMA ASPERGILLUM	5.1(1-35)%
BU GU ZHI	PSORALEA CORYLIFOLIA	5.1(1-30)%
DANG SHEN	CODONOPSIS PILOSULA	6.12(1-30)%
SHAN ZHA	CRATAEGRUS PINNATIFIDA	4.1(1-30)%
MAI YA	HORDEUM VULGARA	2.04(1-30)%
SHEN QU	MASSA FERMENTATA MEDICALIS	2.04(1-30)%
WU WEI ZI	SCHISANDRA CHINENSIS	5.1(1-30)%
SHI GAO	GYPSUM	15.31(1-50)%
SU ZI	PERILLA FRUTESCENS	5.1(1-30)%
BAI SHAO	PAEONIA LACTIFLORA	4(1-30)%

[0009]

	PRESCRIPTION 6
	% amount
Name (pinyin)	Latin Name (species)	(w/w)
XING REN	PRUNUS ARMENIACA	6.12(1-30)%
GAN CAO	ASTER TATARICUS	5.1(1-30)%
HUANG QIN	SCUTELLARIA BAICALENSIS	6.12(1-35)%
HUANG LIAN	COPTIS CHINESIS	6.12(1-35)%
BAI BU	STEMONA SESSILIFOLIA	5.1(1-30)%
CHUAN BEI MU	FRITLLARIA CIRRHOSA	5.1(1-30)%
DI LONG	PHERETIMA ASPERGILLUM	5.1(1-35)%
BU GU ZHI	PSORALEA CORYLIFOLIA	5.1(1-30)%
DANG SHEN	CODONOPSIS PILOSULA	6.12(1-30)%
SHAN ZHA	CRATAEGRUS PINNATIFIDA	4.1(1-30)%
MAI YA	HORDEUM VULGARA	2.04(1-30)%
SHEN QU	MASSA FERMENTATA MEDICALIS	2.04(1-30)%
WU WEI ZI	SCHISANDRA CHINENSIS	5.1(1-30)%
SHI GAO	GYPSUM	15.31(5-50)%
SU ZI	PERILLA FRUTESCENS	5.1(1-30)%
BAI SHAO	PAEONIA LACTIFLORA	4(1-30)%
JIN YIN HUA	LONICERA JAPONICA	5(1-30)%
LIAN QIAO	FORSYTHIA SUSPENSA	6(1-30)%
JING JIE	SCHIZONEPETA TENUIFOLIA	5(1-30)%

[0010]

	PRESCRIPTION 7
	% amount
Name (pinyin)	Latin Name (species)	(w/w)
XING REN	PRUNUS ARMENIACA	6.12(1-30)%
GAN CAO	ASTER TATARICUS	5.1(1-30)%
HUANG QIN	SCUTELLARIA BAICALENSIS	6.12(1-35)%
HUANG LIAN	COPTIS CHINESIS	6.12(1-35)%
BAI BU	STEMONA SESSILIFOLIA	5.1(1-30)%
CHUAN BEI MU	FRITLLARIA CIRRHOSA	5.1(1-30)%
DI LONG	PHERETIMA ASPERGILLUM	5.1(1-35)%
BU GU ZHI	PSORALEA CORYLIFOLIA	5.1(1-30)%
DANG SHEN	CODONOPSIS PILOSULA	6.12(1-30)%
SHAN ZHA	CRATAEGRUS PINNATIFIDA	4.1(1-30)%
MAI YA	HORDEUM VULGARA	2.04(1-30)%
SHEN QU	MASSA FERMENTATA MEDICALIS	2.04(1-30)%
WU WEL ZI	SCHISANDRA CHINENSIS	5.1(1-30)%
SHI GAO	GYPSUM	15.31(5-50)%
SU ZI	PERILLA FRUTESCENS	5.1(1-30)%
BAI SHAO	PAEONIA LACTIFLORA	4(1-30)%
HUANG QI	ASTRAGALUS MEMBRANACEUS	6(1-30)%
FANG FENG	LEDEBOURIELLA DIVARICATA	5(1-30)%
JIN YIN HUA	LONICERA JAPONICA	5(1-30)%
LIAN QIAO	FORSYTHIA SUSPENSA	6(1-30)%
JING JIE	SCHIZONEPETA TENUIFOLIA	5(1-30)%

[0011] In the prescription, JIN YIN HUA (LONICERA JAPONICA) LIAN QIAO (FORSYTHIA SUSPENSA)) JING JIE (SCHIZONEPETA TENUIFOLIA) can be removed.

[0012] Note: In each above-mentioned prescription, the figures shown in parenthesis represent that the percentage amount can vary within the range, for example, (1-30) in LIAN QIAO 6(1-30) % means that the percentage amount of LIAN QIAO can vary from 1 to 30.

[0013] These formulas can be formulated into various dosage forms, for example, the herbs can be ground into powder, mix homogeneously, and then encapsulated into capsules with 0.5 g per capsule. Also, the formulas can be formulated into infusion according to various conventional processes. All of these dosage forms can obtain beneficial effects.

[0014] These prescriptions are based on Ma Xing Shi Gan Tang (Decoction of Ephedra, Apricot, Gypsum and Licorice) and Huang Lian Jie Du Tang (Antidotal Decoction of coptis), and are formed by modification. Among the various components of the prescription, Ma Huang acts as a principle drug, and exerts the effect of facilitating the flow of Lung-Qi to relieve asthma, and its pungent flavor is good at dispelling exogenous factors. Shi Gao plays the role of an assistant drug with the effects of both clearing and purging Lung-heat to restrict the warm property of Ma Huang. Xing Ren, a drug with a bitter taste and warm property, is used as an adjuvant drug to reinforce Ma Huang and Shi Gao in facilitating the flow of the lung-qi to relieve asthma. Gan Cao is used as a guiding drug for replenishing Qi and regulating the middle-warmer, and coordinating the effect of various drugs in case the cold and heavy property of Shi Gao impairs the stomach. In the Huanglian Jiedu Tang, ingredient Huang Lian is used as principal drug, which plays a significant role of purging pathogenic fire in the heart and middle-energizer; Huang Qin acts as an assistant drug with the effect of clearing away heat in the lung and purging fire in the upper-energizer; Huang Bai is used as both an adjuvant and guiding drug, the former providing the effect of purging pathogenic fire in lower-energizer and the latter have the effect of removing pathogenic fire in the tri-energizer by inducing diuresis. In the prescriptions of the present invention, Su Zi relieves cough and asthma, descends Qi to remove phlegm, and moisten the intestines to loosen the bowels, which is used together with Xing Ren; Kuan Dong Hua moistens the lung and lowers Qi, resolves phlegm and relieves cough and assists Xing Ren and Bei Mu; Bai Bu and Bei Mu resolve phlegm to stop coughing; Di Long expels wind to relieve spasm, expand bronchus, clear away heat from the lung to relieve asthma, which is used with Ma Huang, Xing Ren and Shi Gao; Wu Wei Zi astringes the lung and nourishes the kidney; Dang Shen invigorates the spleen and replenishes the Qi and is useful for insufficiency of the lung-qi consumption; Bu Gu Zhi tonifys the kidney and strengthens the Yang, which is used with Dang Shen and Wu Wei Zi to astringe the lung-qi; Shan Zha, Mai ya, and Shen Qu strength the spleen and improve digestion in order to prevent the drugs from replenishing Qi and blood (Yi Qi Bu Xue Yao) from growing loathful Qi to block the spleen and stomach's function of transport and digestion. The various components in the prescriptions cooperate with each other so that the action of the whole formula is tonifying but not stagnant, and is purgation but not asthenia. So the formulas increase the organism's immunity function and dilate bronchi to stop asthma.

THE BENEFICIAL EFFECT OF THE INVENTION

[0015] The composition of the present invention can be formulated into capsule and infusion, in which Asthma-Relieving Infusion (Ping Chuan Chong Ji, hereinafter referred to as PCCJ), a dosage form of the above-mentioned prescriptions prepared according to various conventional technologies, has been used for more than 20 years in China and more than 5 years in Israel. The treatment of bronchial asthma can be divided into two stages: attack stage and remission stage. During the attack stage, the curative effect of PCCJ is not faster than those of western medicines, but it is better than western medicines in the remission stage. The principle lays in that the treatment of cough and dyspnea concerns not only lung, but also kidney function, and the symptoms of the lung are treated in the attack stage, while therapies for tonifying the kidney are applied in the remission stage. Based on the whole body, PCCJ pays more attention to elaborating the body's potential energy and strengthening the body's resistance to the disease, therefore it can be useful for treating allergic and non-allergic asthma. The morbidity rate of asthma has been getting higher year by year in the past ten years, which may be related to the misunderstanding of asthmatic pathogenesis and wrong therapy. In the past years, it is the classical pathologic theory that bronchospasm is the main pathologic change of asthma. The new concept of asthma's pathologic mechanism put forward by some universities is that airway allergic inflammation is the pathologic change of asthma, and it is found in airway lavage solution that there are more eosinocytes and macrophages than mast cells, which induce the attack of asthma more readily. Among inflammatory mediators, the bioactivity of platelet activating factor (PAF) is much stronger than those of interleukin, prostaglandin as well as histamine, whose pathogenic effect is 1000 times stronger than that of histamine, thus it is the eosinophilic chemotactic factor with stronger activity. The bronchodilator has been used as the first therapy of bronchus asthma for forty years. Studies have showed that the high sensitive state of bronchus is the main reason for the worsening of asthma because a long-term use of bronchodilator may conceal the development of inflammation to cause the patients' symptoms to worsen, which is the main reason why asthmatic mortality is increasing year by year. At present, adrenal cortical hormone is an effective anti-airway-inflammatory drug, and it can act on many aspects of asthma. But 80% patients respond well to adrenal cortical hormone, while 20% percent of patients do not, because of a decreased number of receptors for adrenal cortical hormone on the cell surface of the patient. Systemic therapy with hormones induces the inhibition of hypothalamic-pituitary-adrenal axis, which may cause the patient to be dependent on the hormone, and latent inflammation diffusion. For most patients, if the hormone is inhaled at a rate of more than 1600 μg per day for three months, their hypothalamic-pituitary-adrenal axis will be inhibited and even the function of adrenal cortical hormone. When they stop inhaling the hormone, asthma will easily recur. The inventor of the present invention made Ping Chuan Chong Ji from traditional Chinese medicines to treat asthma. The PCCJ can relieve or cease the attack of asthma, improve pulmonary function, regulate the immunological function, enhance T cells and decrease IgE, inhibit airway allergic reaction, relieve high sensitive state of airway and reduce side effects and administrating dose of hormone, and even finally, make patients cease the administration of hormones. The effective rate of PCCJ is clinically 93%. To further prove the clinical efficacy, the clinical trials were made in Tel-ashomer hospital of Israel, the results are showed as follows.

[0016] A. Method

[0017] Subject: Outpatients suffered from asthma attack. The asthma was classified as the type of lung-heat with deficiency in organ and excess in superficiality in traditional Chinese medicine. The standards of diagnosis and judgment in the condition of the patient are in accordance with “Principle of Clinical Study of New Drugs (Chinese drug)”.

[0018] After a two-week run-in period of treatment with a placebo, 28 patients were divided into two groups randomly. A double-blind and placebo-controlled study was conducted to evaluate the clinical efficacy of PCCJ in terms of symptom scores, morning and evening PF, and changes of immunoregulatory function. There were 15 patients in test group, 12 females and 3 males, with an average age of 43 (19-68) years old and the average duration of disease of 20.5 years, including 1 patient with mild asthma, 13 patients with moderate asthma and 1 patient with serious asthma. Among the patients of the test group, there were 4 patients with endogenous asthma, 4 patients with exogenous asthma and 7 patients with mixed type of asthma. There were 13 patients in the control group, 7 females and 6 males, with the average age of 46(18-68) years and the average duration of disease of 18.5 years, including 3 patients with mild asthma, 9 patients with moderate asthma and 1 patient with serious asthma. Among the patients of the test group, there were 4 patients with endogenous asthma, 4 patients with exogenous asthma and 5 patients with mixed type of asthma.

[0019] B. Trial Design

[0020] This trial was conducted using two groups of patients in a double-blind, randomized, parallel-grouped manner. It was carried out in Tel-Hashomer hospital of Israel. All patients agreed to conduct the trial by witnessed oral and written form.

[0021] The trial includes a 2 week run-in period (period 1), a 4 week controlled period (period 2), a 4 week titration period (period 3) and a 4 week open period (period 4). There were 6 scheduled visits to the clinic: at the start of run-in period, at the start of the treatment, 2 weeks after the treatment, and then 4, 6, 8, and 10 weeks after the treatment.

[0022] All patients entering the run-in phase received a placebo at a dose of 5 capsules per time, 3 times daily, and if necessary, administrated additionally western medicine. At the end of the run-in period, the patients were randomly assigned to receive either of the following treatments, administrating PCCJ or the placebo (5 capsules for each agent, 3 times daily) for a period of two months.

[0023] The whole trial was designed to divide into stages A, B, C, D. A: 2 week run-in period, all patients took placebo together with conventional western medicine; B: 4 week treatment period, the patients took PCCJ or the placebo together with conventional western medicine; C: 4 week treatment period, the patients did their best to reduce the dosage of conventional western medicine; D: the patients in the control group were given PCCJ for one month.

[0024] C. Diary-Card Data

[0025] Patients filled in a daily diary during the run-in and treatment periods, recording the better value of peak expiratory flow before administration in the morning and evening detected with a standard pneumatometer; Symptoms of asthma during the night or the daytime (based on scoring with 5 scales with 0 indicating no symptom and more than 3 representing severe symptom); the times of awakening due to asthma; the times and dosage of inhaling hormones and bronchodilator (including those at night and those during daytime); and the dosage of the western medicines given by oral route.

[0026] D. Clinic Visits

[0027] At each of the scheduled clinic visits, a questionnaire included emotional status and asthma symptoms, including coughing, phlegm, and dyspnea, some clinical measures, including rale of lung, the heart rates (HR) and blood pressure (BP); adverse effects; withdrawals from the trial, or reducing and stopping the administration of western medicines. Diary cards were reviewed, and lung functions (FVC, FEV1, and FEV1%) were measured with the lung function instrument. In addition, IgE, cholesterol, and blood count were detected too.

[0028] Episode-Free Days

[0029] An episode-free day was a day of optimally controlled asthma. That is to say, it is not necessary to inhale any hormone and bronchodilator, the score of asthma symptom was 0, peak expiratory flow appeared in morning was up to 80 percent and there is no adverse event.

[0030] E. Treatment

[0031] In the test group, the patients took Ping Chuan Chong Ji orally. PCCJ is not only a symptom-treating drug but also a cause-treating drug, containing EPHEDRA SINICA, PERILLA FRUTESCENS, PRUNUS ARMENIACA, CODONOPSIS PILOSULA etc. 5 capsules each time, 3 times daily. One course of treatment consists of 2 months. The patients in the control group took placebo, 5 capsules each time, 3 times daily. One course of treatment consists of two months. The patients with serious asthma were given additionally hormone.

[0032] F. Statistical Analysis

[0033] The date analysis followed a factorial design, and pairwise comparisons were made by t test and ANOVA.

[0034] G. Results

[0035] 28 patients were randomly divided into two groups. The differences of symptoms, pulmonary function, PF and so on in base-line data between the groups were minor and insignificant. There were 15 and 13 patients in the treatment group and the control group, respectively. In the control group, 2 patients were given additional hormone because of worsening asthma. However, in the treatment group, no patient was given additional hormone, and the dosage of hormone was reduced. Some of them even completely stopped the administration of hormone without recurrence found by following up for half year after the trial.

[0036] H. The Judgment Standard of Curative Effects

[0037] Clinically controlled: the asthmatic's symptoms and wheeze vanish or become less than a mild degree; markedly effective: the asthmatic's symptoms and wheeze are improved significantly (+++−−+); effective: the asthmatic's symptoms and wheeze are improved slightly (+++−−++−−+); ineffective: the asthmatic's symptoms and wheeze are not improved or even exacerbated.

[0038] I. The Clinical Curative Effects

[0039] In the test group (PCCJ group), 3 cases (20%) were clinically controlled, 5 cases (33%) were markedly effective; 6 cases (40%) were effective and 1 case (7%) was ineffective. In control group, 6 cases (46%) were effective and 7 cases (54%) were ineffective. The total effective rate was 93% in the test group and 46% in the control group. A significant difference was founded between the two groups (P<0.05).

[0040] Symptom

[0041] 1. Cough, Phlegm, Shortness of Breath, and Wheeze

[0042] At the end of the run-in period, the patients received 5 capsules, 3 times per day. As a result, the scores of the clinical symptom in PCCJ group were significantly decreased, while no improvement was found in control group (table 1).

TABLE 1
The changes of cough, phlegm, shortness of breath, and
wheeze's scores (mean ±SE)
	Period 1	Period 2	Period 3
	(run-in)	(controlled)	(titration)
Groups	N	Symptoms	(score)	(score)	(score)
PCCJ	15	cough	1.600 ± 0.235	0.333 ± 0.126*	0.200 ± 0.145*
	15	phlegm	1.533 ± 0.236	0.400 ± 0.131*	0.200 ± 0.107*
	15	short of breath	2.200 ± 0.175	0.733 ± 0.248*	0.53 ± 0.256*
	15	wheeze	1.467 ± 0.274	0.333 ± 0.187*	0.267 ± 0.206*
control	13	cough	1.154 ± 0.249	1.385 ± 0.385	1.462 ± 0.386
	13	phlegm	1.250 ± 0.231	1.154 ± 0.274	1.231 ± 0.303
	13	short of breath	2.143 ± 0.340	1.714 ± 0.286	2.143 ± 0.340
	13	wheeze	0.846 ± 0.249	1.000 ± 0.3	0.923 ± 0.288
Notes:
*p < 0.0001, compared with period 1 (run-in period).

[0043] 2. Day and Night

[0044] Compared to those in the control group, the symptoms during the day and night were controlled very significantly in the PCCJ group (table 2).

TABLE 2
The changes of the symptoms' score of day and night (mean ±SE)
	period 1	period 2	period 3
	(run-in)	(controlled)	(titration)
Groups	N	symptoms	(score)	(score)	(score)
PCCJ	15	day	3.133 ± 0.350	0.600 ± 0.190*	0.400 ± 0.214*
	15	night	1.933 ± 0.483	0.333 ± 0.187*	0.133 ± 0.091*
control	13	day	2.846 ± 0.355	2.615 ± 0.401	2.923 ± 0.431
	13	night	1.769 ± 0.455	1.462 ± 0.447	2.154 ± 0.478
Notes:
*p < 0.0001, compared with period 1 (run-in period).

[0045] 3. Lung Function

[0046] FVC was increased significantly in PCCJ group during the treatment, while no improvement was found in the control group. The mean FEV1 of the base line was 51.8%, however, two weeks after administration and one month after administration, it was increased up to 64.133% and 65.867%, respectively. But the control group had no improvement (table 3).

TABLE 3
The changes of FVC (L%) and FEV1 (L/S %) (mean ±SE)
	lung	period 1	period 2	period 3
Groups	N	function	(run-in)	(controlled)	(titration)
PCCJ	15	FVC	64.867 ± 4.412	79.600 ± 3.169**	79.800 ± 3.468**
	15	FEV1	51.800 ± 5.170	64.133 ± 4.634*	65.867 ± 4.895*
Control	13	FVC	75.154 ± 6.214	76.385 ± 6.447	74.467 ± 5.760
	13	FEV1	63.231 ± 7.322	64.000 ± 7.476	61.615 ± 6.479
Notes:
*p < 0.0015;
**p < 0.0003, compared with period 1 (run-in period).

[0047] 4. Peak Expiratory Flow Rates

[0048] The peak expiratory flow rate was increased from 25 liters per minute before administration to 33.6 liters per minute in PCCJ group (P<0.0001), and no improvement was found in the Control group (table 4).

TABLE 4
The changes of Peak Expiratory Flow Rates (mean ±SE)
	period 1	period 2	period 3
	lung	(run-in)	(controlled)	(titration)
groups	N	function	(M)	(M)	(M)
PCCJ	15	PF	250 ± 14.768	330.667 ± 19.085*	336 ± 18.434*
Control	13	PF	299.231 ± 35.018	290 ± 30.530	294.615 ± 30.668
Notes:
*p < 0.0001, Compared with period 1 (run-in period).

[0049] 5. The Change of IgE

[0050] IgE was lowered only in PCCJ group rather than the control group (table 5).

TABLE 5
The change of IgE (mean ±SE)
	period 1	period 2
	(run-in)	(controlled)
groups	N	IgE	(IU/ML)	(IU/ML)
PCCJ	14	IgE	193.931 ± 41.4	120.380 ± 24.93*
Placebo	10	IgE	286.706 ± 68.142	304.229 ± 71.699
Notes:
*p < 0.067, compared with period 1 (run-in period).

[0051] 6. Cholesterol

[0052] PCCJ was able to reduce the level of cholesterol in the blood, while the level of cholesterol in control was not changed significantly (table 6).

TABLE 6
The change of the level of cholesterol in blood (mean ±SE)
	period 1	period 2
	(run-in)	(controlled)
groups	N	cholesterol	(mg %)	(mg %)
PCCJ	15	cholesterol	226.067 ± 10.882	211.067 ± 9.737*
Control	11	cholesterol	205.455 ± 13.003	207.091 ± 15.589
Note:
*p < 0.0073, compared with period 1 (run-in period).

[0053] 7. The PCCJ Significantly Reduced the Attack of Asthma

TABLE 7
The changes of asthma's attack (mean ±SE)
	period 1	period 2	period 3
	(run-in)	(controlled)	(titration)
Groups	N	(score)	(score)	(score)
PCCJ	15	2.4 ± 0.335	0.4 ± 0.190*	0.333 ± 0.159*
Control	13	2.308 ± 0.398	2.154 ± 0.436	2.308 ± 0.365
Note:
*P < 0.0001, compared with period 1 (run-in period).

[0054] 8. PCCJ Reduced the Administrating Dosage of Ventolin (Salbutamol)

TABLE 8
The change of the dosage of Ventolin (mean ±SE)
	period 1	period 2	period 3
	(run-in)	(controlled)	(titration)
	puff	puff	puff
groups	N	(100 μg)	(100 μg)	(100 μg)
PCCJ	15	3.667 ± 0.583	1.267 ± 0.396*	0.667 ± 0.252*
Control	12	3.417 ± 0.811	3.167 ± 0.878	3.333 ± 0.762
Note:
*p < 0.0001, compared with period 1 (run-in period).

[0055] 9. The PCCJ Reduced the Dosage of Flixotide

TABLE 9
The change of the dosage of Flixotide (Mean ±SE)
	Period 1	Period 2	Period 3
	(run-in)	(controlled)	(titration)
Groups	N	(μg)	(μg)	(μg)
PCCJ	7	714.286 ± 101.015	178.571 ± 89.879*	250 ± 77.152*
Control	11	318.182 ± 71.060	363.636 ± 91.476	386.364 ± 91.476
Note:
*p < 0.0038, compared with period 1 (run-in period).

[0056] 10. PCCJ Reduced the Dosage of Budicort (table 10).

TABLE 10
The change of the dosage of Budicort (mean ±SE)
	Period 1	Period 2	Period 3
	(run-in)	(controlled)	(titration)
Groups	N	(mg)	(mg)	(mg)
PCCJ	11	0.455 ± 0.61	0.218 ± 0.078*	0.127 ± 0.041*
Control	11	0.218 ± 0.063	0.2 ± 0.060	0.273 ± 0.078
Note:
*p < 0.0001, compared with period 1 (run-in period).

[0057] 11. PCCJ Reduced the Dosage of Serevant (table 11).

TABLE 11
The changes of the dosage of Serevant (mean ±SE)
	Period 1	Period 2	Period 3
	(run-in)	(controlled)	(titration)
Groups	N	(μg)	(μg)	(μg)
PCCJ	9	23.000 ± 3.391	16.000 ± 3.279*	15 ± 1.5*
Control	10	15.3 ± 4.253	15.3 ± 4.253	14.4 ± 4.285
Note:
*p < 0.0661, compared with period 1 (run-in period).

[0058] 12. PCCJ was Able to Regulate the T Cell Subgroup.

TABLE 12
The changes of T Cell Subgroup before and after Treatment (mean ±SD)
	CD2	CD4	CD8
Groups		N	(%)	(%)	(%)	CD4/CD8
healthy		10	83 ± 6.9	58.8 ± 6.3	25.9 ± 2.6	2.2 ± 0.25
person
PCCJ	before treatment	25	56.4 ± 11.6Δ	32.1 ± 11Δ	40.6 ± 14.1Δ	0.9 ± 0.4Δ
	after treatment	25	65.3 ± 14*	47.5 ± 12.5*	27.5 ± 5*	1.8 ± 0.34**
Control	before treatment	8	50.3 ± 6.4Δ	37 ± 8.5Δ	36.1 ± 10.1Δ	1.2 ± 0.6Δ
	after treatment	8	48 ± 6.3	36 ± 11.4	32.6 ± 15.1	1.3 ± 0.65
Note:
compared with healthy personΔ, P < 0.01; compared with before treatment,
*P < 0.05;
**p < 0.01.

[0059] The results showed that before treatment, the percents of CD2 and CD4 in two groups were lower than those of the healthy people, the percents of CD8 were higher than those of the healthy people and the ratios of CD4/CD8 were lower than those of the healthy people. This suggested that during acute asthma attack, the patients had the disorder of T cell subgroups. After treatment, CD2, CD4 and the ratio of CD4/CD8 were increase significantly, while CD8 was lowered. However, no significant change was found in the control group.

[0060] Discussion

[0061] The observations proved that the PCCJ was able to relax the smooth muscle of bronchus, which was useful to treat the acute attack of asthma and exert the function of anti-airway allergic inflammation to cease the attack of asthma. At the same time, the Chinese herbal medicines tonifying kidney also prevented the asthma's attack. T lymphocyte subgroups play an important regulative role in hormonal immunity. In recent years, it is was found that T cell regulated the formation of IgE, and when lymphocytes were cultured, TH clone prompted B cell to secret more IgE. Some patients belong to the IgE-dependent type, who has a higher level of IgE in blood serum, and IgE results in the releasing of mediator after mast cells have been cross-linked, which brings about bronchospasm or acute attack. In the meantime, it was also found that patients of asthma have a decreased TH in the peripheral blood and an increased TH in the lung tissue, and it lasted for a long time. This suggested that TH migrated to lung and played an important role in the production of type 1 allergic reaction. PCCJ was able to regulate T cell subgroups and prevented the attack of asthma, and increased CAMP in plasma, protected and increased lung cells type 2, and recovered the lung function to the normal level. Moreover, it was also able to reduce the dosage or even stop the administration of hormone. The animal experiment showed that PCCJ had no side effects even if it was took with 214 times dosage as high as the normal for 1 week and 80 times dosage for 3 months. So long tern use of the drug of the present invention can treat the asthma efficiently and safely.

THE SPECIFIC MODE FOR CARRYING OUT THE INVENTION

[0062] The Chinese herbal medicines used in each prescription are available commercially in China. The various medicinal herbs were weighed according to the herbs employed and their percentage showed in the prescription, and then ground to powder, which encapsulated into capsule, 0.5 g per capsule.

Claims

1. A composition for treatment of asthma, being made from a part or all of the following Chinese herbal medicines: Ma Huang (EPHEDRA SINICA), Xing Ren (PRUNUS ARMENIACA), Gan Cao (GLYCYRRHIZA URALENSIS LICORICE), Huang Qin (SCUTELLARIA BAICALENSIS), Huang Lian (COPTIS CHINESIS), Huang Bai (PHELLODENDRON CHINENSE), Kuang Dong Hua (TUSILAGO FARFARA), Bai Bu (STEMONA SESSILIFOLIA), Chuan Bei MU or Bei MU (FRITLLARIA CIRRHOSA), Di Long (PHERETIMA ASPERGILLUM), Bu Gu Zhi (PSORALEA CORYLIFOLIA), Dang Shen (CODONOPSIS PILOSULA), Shan Zha (CRATAEGRUS PINNATIFIDA), Ma Ya (HORDEUM VULGARA), Shen Qu (MASSA FERMENTATA MEDICALIS), Wu Wei Zi (SCHISANDRA CHINENSIS), Shi Gao (GYPSUM), Su Zi (PERILLA FRUTESCENS), Zi Wan (ASTER TATARICUS), Bai Shao (PAEONIA LACTIFLORA), Jin Yin Hua (LONICERA JAPONICA), Lian Qiao (FORSYTHIA SUSPENSA), Jing Jie (SCHIZONEPETA TENUIFOLIA), Huang Qi (ASTRAGALUS MEMBRANACEUS), Fang Feng (LEDEBOURIELLA DIVARICATA).

2. A composition for treatment of asthma according to claim 1, being made from the following Chinese herbal medicine:

3. A composition for treatment of asthma according to claim 1, being made from the following Chinese herbal medicine:

4. A composition for treatment of asthma according to claim 1, being made from the following Chinese herbal medicine:

5. A composition for treatment of asthma according to claim 1, being made from the following Chinese herbal medicine:

6. A composition for treatment of asthma according to claim 1, being made from the following Chinese herbal medicine:

7. A composition for treatment of asthma according to claim 1, being made from the following Chinese herbal medicine:

8. A composition for treatment of asthma according to claim 1, being made from the following Chinese herbal medicine:

9. A composition for treatment of asthma according to any one of claims 1-8, being a pharmaceutically acceptable dosage form.