TRADITIONAL CHINESE MEDICINE COMPOSITION FOR TREATING INTERSTITIAL PULMONARY FIBROSIS AND METHOD FOR MAKING SAME

Abstract

Disclosed herein is a traditional Chinese medicine composition for treating interstitial pulmonary fibrosis, which is prepared from 10-20 parts by weight of Radix salviae miltiorrhiza, 4-8 parts by weight of peach kernel, 2-4 parts by weight of hirudo, 5-15 parts by weight of Radix paeoniae rubra, 5-15 parts by weight of Radix ophiopogonis, 5-15 parts by weight of Chebulae fructus immaturus and 2-4 parts by weight of Oroxylum indicum (Linn.) Kurz. The invention also provides a method of preparing the composition.

Claims

1. A composition for treating interstitial pulmonary fibrosis, wherein the composition is prepared from 10-20 parts by weight of Radix salviae miltiorrhiza, 4-8 parts by weight of peach kernel, 2-4 parts by weight of hirudo, 5-15 parts by weight of Radix paeoniae rubra, 5-15 parts by weight of Radix ophiopogonis, 5-15 parts by weight of Chebulae fructus immaturus and 2-4 parts by weight of Oroxylum indicum (Linn.) Kurz.

2. The composition of claim 1, wherein the composition is prepared from 15 parts by weight of Radix salviae miltiorrhiza, 6 parts by weight of peach kernel, 3 parts by weight of hirudo, 10 parts by weight of Radix paeoniae rubra, 10 parts by weight of Radix ophiopogonis, 10 parts by weight of Chebulae fructus immaturus and 3 parts by weight of Oroxylum indicum (Linn.) Kurz.

3. A method of preparing the composition of claim 1, comprising: mixing Radix salviae miltiorrhiza, peach kernel, hirudo, Radix paeoniae rubra, Radix ophiopogonis, Chebulae fructus immaturus and Oroxylum indicum (Linn.) Kurz in a mass ratio of 10-20: 4-8: 2-4: 5-15: 5-15: 5-15: 2-4; extracting the reaction mixture by decoction with water in a mass ratio of 1:10 for 2 h to collect a first extract; extracting the reaction mixture again by decoction with water in a mass ratio of 1:8 for 2 h to collect a second extract; combining the first extract with the second extract; filtering the combined extract; concentrating the filtrate under vacuum to produce a paste with a relative density of 1.15 at 60 C.; drying the paste under vacuum followed by pulverization to produce dried powder; and mixing the dried powder with dextrin and stevioside uniformly followed by granulation and drying to produce the composition.

4. A method of treating interstitial pulmonary fibrosis in a patient in need thereof, comprising: administering an effective amount of the composition of claim 1 to the patient.

Description

DETAILED DESCRIPTION OF EMBODIMENTS

[0016] The invention will be further described in detail below with reference to the embodiments, and these embodiments are not intended to limit the invention. Any modifications, changes and replacements made without departing from the spirit of the invention should fall within the scope of the invention.

Example 1

[0017] Radix salviae miltiorrhiza, peach kernel, hirudo, Radix paeoniae rubra, Radix ophiopogonis, Chebulae fructus immaturus and Oroxylum indicum (Linn.) Kurz were mixed in a mass ratio of 15:6:3:10:10:10:3 and extracted with water by decoction in a mass ratio 1:10 for 2 h to collect a first extract. Then the reaction mixture was extracted again with water by decoction in a mass ratio of 1:8 for 2 h to collect a second extract. The first extract and the second extract were combined and filtered. The filtrate was concentrated under vacuum to produce a paste with a relative density of 1.15 at 60 C. The paste was dried under vacuum, pulverized, mixed with dextrin and stevioside uniformly, granulated and dried to produce a medicine composition for treating interstitial pulmonary fibrosis.

Example 2

[0018] Radix salviae miltiorrhiza, peach kernel, hirudo, Radix paeoniae rubra, Radix ophiopogonis, Chebulae fructus immaturus and Oroxylum indicum (Linn.) Kurz were mixed in a mass ratio of 10:8:2:15:5:15:2 and extracted with water by decoction in a mass ratio 1:10 for 2 h to collect a first extract. Then the reaction mixture was extracted again with water by decoction in a mass ratio of 1:8 for 2 h to collect a second extract. The first extract and the second extract were combined and filtered. The filtrate was concentrated under vacuum to produce a paste with a relative density of 1.15 at 60 C. The paste was dried under vacuum, pulverized, mixed with dextrin and stevioside uniformly, granulated and dried to produce a medicine composition for treating interstitial pulmonary fibrosis.

Example 3

[0019] Radix salviae miltiorrhiza, peach kernel, hirudo, Radix paeoniae rubra, Radix ophiopogonis, Chebulae fructus immaturus and Oroxylum indicum (Linn.) Kurz were mixed in a mass ratio of 20:4:4:5:15:5:4 and extracted with water by decoction in a mass ratio 1:10 for 2 h to collect a first extract. Then the reaction mixture was extracted again with water by decoction in a mass ratio of 1:8 for 2 h to collect a second extract. The first extract and the second extract were combined and filtered. The filtrate was concentrated under vacuum to produce a paste with a relative density of 1.15 at 60 C. The paste was dried under vacuum, pulverized, mixed with dextrin and stevioside uniformly, granulated and dried to produce a medicine composition for treating interstitial pulmonary fibrosis.

Example 4

Clinical Experiment

[0020] 40 cases suffering from acutely-exacerbated interstitial pulmonary fibrosis were selected for clinical observation in 2016-2018. All patients were routinely treated with glucocorticoid and an inhaled bronchodilator, and patients in the treatment group were further treated with the composition prepared in Example 1 (Feixian Formula). After treated for 3 weeks, the patients were evaluated through the traditional Chinese medicine symptom complex score, where the score standards were shown in Table 1 and the results were shown in Table 2. It can be seen from Table 2 that the symptom complex scores of the treatment group were all higher than those of the control group. Moreover, the patients treated with the Feixian Formula were clinically observed to be correspondingly improved in the objective indexes (as shown in Table 3).

[0021] The clinical test was performed as follows.

1. Diagnostic Criteria

1.1 Western Medicine Diagnostic Criteria

[0022] Interstitial pulmonary fibrosis was derived from various etiological factors, including primary interstitial pulmonary fibrosis and secondary interstitial pulmonary fibrosis. The chest HRCT showed the change of the interstitial pulmonary fibrosis, and Veclro rale can be diagnosed by lung auscultation. Moreover, the acropachy was present or absent. The pulmonary function test showed the restricted ventilation function disturbance.

[0023] The appropriate patients were required to involve the clinical manifestations of aggravated cough, chest tightness and asthma.

1.2 Traditional Chinese Medicine Syndrome Diagnostic Criteria

[0024] The syndrome of yin deficiency and blood stasis was mainly characterized by: repeated cough predominated by dry cough; afternoon tidal fever; dysphoria with feverish sensation in chest; mouth and throat dryness; local tingling; cough with shortness of breath and chest tightness; red tongue with dark purple air or tongue spots; thready and uneven pulse or thready and rapid pulse.

2. Selection Criteria

2.1 Inclusion Criteria

[0025] (1) 18-75 years old;

[0026] (2) Meeting the Western medicine diagnostic criteria for interstitial pulmonary fibrosis and being in the acute exacerbation stage;

[0027] (3) Meeting the traditional Chinese medicine syndrome diagnostic criteria for yin deficiency and blood stasis; and

[0028] (4) Being informed; voluntarily agreeing to receive the treatment; and signing an informed consent form.

[0029] Any one complying the above 4 criteria can be included in the cases.

2.2 Exclusion Criteria

[0030] (1) Under 18 or over 75; pregnant or lactating women; and allergic to this medicine;

[0031] (2) Suffering from severe primary diseases such as diabetes, liver, kidney, brain and hematopoietic diseases, or mental illness; and

[0032] (3) Failing to meet the inclusion criteria; failing to take the medicine as prescribed; failing to determine the efficacy or safety.

2.3 Case Exclusion and Dropping-Out and Trial Suspension

[0033] Doctors participating in clinical trials should carefully record the reasons for the exclusion, dropping-out and suspension, the relationship with the trial and the evaluation at the time of suspension. The withdrawal depending on the organizer was defined as exclusion, while the withdrawal depending on the subject was defined as dropping-out. The specific regulations were described as follows:

[0034] (1) Subjects with poor compliance; failing to take the drug as prescribed; or involving an efficacy failing to be determined or incomplete data to affect the judgment of efficacy and safety, should be excluded.

[0035] (2) Subjects involving serious adverse event; involving complications or special physiological changes; or unsuitable for the subsequent test, should be excluded.

[0036] (3) Subjects involving insignificant therapeutic effect; failing to participate in the subsequent clinical trial for some reasons such as adverse event or fear; or withdrawing without any reason, are deemed to be dropped out.

[0037] (4) In the case that during the trial, serious safety problem occurs or the drug is observed to be not good enough in efficacy or to be ineffective, the trial may be suspended.

3. Case Source and Grouping

[0038] 40 cases were selected from outpatient and inpatients in the Traditional and Western Medicine Hospital in Jiangsu, and randomly and averagely divided into two groups, i.e., the treatment group and the control group.

4. Trial

4.1 Drug Administration

[0039] The treatment group and the control group were both routinely treated with western medicines including glucocorticoids, expectorants and inhaled bronchodilators. Moreover, the treatment group was further treated with the Fuxian Formula prepared in Example 1.

4.2 Observation

[0040] The medication was observed for 1 month, and the follow-up was performed once respectively before and after the observation. Moreover, the follow-up was also performed once respectively on the 3.sup.rd, 7.sup.th and 14.sup.th day of the course, and the conditions were recorded on the TCM symptom score table. Except for those suffering from serious adverse reactions, the follow-up was generally not performed any more after the observation period. Those suffering from serious adverse reactions or involving obvious abnormal values in the safety examination should be followed up or re-examined for the abnormal items.

4.3 Indexes and Recording Method

(1) Safety Observation

[0041] The observation for the safety was performed once respectively at the beginning and end of the course.

[0042] 1-1 General physical examination items: body temperature, breathing, pulse and blood pressure;

[0043] 1-2 Routine tests for blood, urine and stool;

[0044] 1-3 ECG, liver function (ALT), renal function (BUN, Cr).

(2) Therapeutic Effect Observation

[0045] 2-1 TCM syndromes and scores: TCM symptoms (including cough, asthma, shortness of breath, cyanosis); physical signs (tongue and pulse); calculation of the scores before and after treatment; changes of the total syndrome score.

[0046] 2-2 Effect on the objective indexes

[0047] Examination for the lung function FVC and DLCO was performed respectively before and after the treatment.

4.4 Clinical Efficacy Evaluation Index

[0048] The standard of TCM syndrome efficacy is evaluated according to the guidelines for clinical research of new Chinese medicines and actual conditions.

TABLE-US-00001 TABLE 1 TCM Syndrome Scoring Standards for Pulmonary Interstitial Fibrosis Symp- Items toms Score 0 2 4 6 Cough No Slight cough Moderate cough, Frequently without affecting coughing during coughing, the daily life the day or night, intolerable tolerable Cyanosis No Occurring after Occurring after Occurring strenuous activ- the activity and any time ities disappearing after a rest Asthma or No Occurring Occurring during Occurring shortness occasionally after most daily activ- any time of breath strenuous activ- ities, but absent ities without during a rest affecting life Frequency No 1-5 times one 5-10 times one More than of cough day, each within day, each for 10 times 2 min 2-5 min one day, each for more than 5 min Fatigue No Slight metal Metal fatigue Extreme fatigue metal

4.5 Evaluation Method

[0049] Yin deficiency and blood stasis syndrome caused by interstitial pulmonary fibrosis was evaluated and scored according to the following formula:

(Symptom score before treatmentSymptom score after treatment)Symptom score before treatment100%.

[0050] (1) Clinical control: clinical symptoms and signs disappeared or basically disappeared, and syndrome score were decreased by 95% or more;

[0051] (2) Significant effect: clinical symptoms and signs were improved significantly, and syndrome scores were reduced by 70%-95%;

[0052] (3) General effect: clinical symptoms and signs were improved, and syndrome scores were decreased by 30%-70%;

[0053] (4) Free of effect: clinical symptoms and signs were not improved significantly, or even worsened, and the syndrome scores were decreased by 0%-30%.

4.6 Data Processing and Statistical Analysis

[0054] The data processing and statistical analysis were performed using SPSS 19.0, and the results were represented by meanSD. The comparison between the two groups was made by t test, and the comparison between the group before and after the treatment was performed using paired t test. P<0.05 indicated that the difference was of statistical significance.

5. Results

5.1 Safety Index

[0055] The blood, urine, stool routine test, electrocardiogram, liver function (ALT), and renal function (BUN, Cr) indexes of the treatment group before and after the observation all did not show clinical abnormalities, demonstrating that the invention had excellent safety.

5.2 Therapeutic Indexes

[0056] It can be seen from Table 2 that the treatment group was superior to the control group both in the scores of the symptoms and signs. As shown in Table 3, the patients who treated with the Feixian Formula were clinically observed to be accordingly improved in the lung function indexes such as FVC and DLCO.

TABLE-US-00002 TABLE 2 Comparison of clinical efficacies for the two groups before and after the treatment Total Significant General Free of effective effect effect effect cases and Group n (cases)/(%) (cases)/(%) (cases)/(%) rates (%) Treatment 20 12 (60.00) 8 (40.00) 0 (0) 20 (100.00) group Control 20 10 (50.00) 8 (40.00) 2 (10.00) 18 (90.00) group

[0057] It can be seen from Table 2 that the treatments respectively for the two groups had significant clinical efficacy, and the therapeutic effect on the treatment group was better than that of the control group.

TABLE-US-00003 TABLE 3 Comparison of lung function indexes between two groups before and after treatment DLCO (mL .Math. Group PVC (L) mmHg.sup.1 .Math. min.sup.1) Treatment group Before 1.58 0.23 45.1 10.6 (n = 20) After 1.86 0.43 59.2 11.4 Control group Before 1.61 0.21 44.2 10.2 (n = 20) After 1.77 0.23 52.2 13.1 Notes: the comparisons were performed using t test at P < 0.05.

[0058] It is apparent that the above embodiments are merely illustrative of the invention, and are not intended to limit the invention. Various modifications, variations and replacements made by those skilled in the art without departing from the spirit of the invention should fall within the scope of the invention.