WO2004108216A1 - The pharmaceutical use of total glucide of peony - Google Patents

Abstract

This invention discloses the use of total glucosides peony of producing a medicament which can treat or prevent from primary sicca syndrome, Behcet's disease, pulmonary interstitial fibrosis, fibromuscular pain syndrome, ankylosing spondylitis, liver fibrosis, systemic lupus erythematosus and so on.

Description

 Application of total glucosides of paeony in pharmacy

 The invention relates to the application of total glucosides of paeony, in particular to its application in the field of pharmaceuticals. Background technique

 Paeonia lactiflora is a commonly used traditional Chinese medicine. Traditional Chinese medicine believes that it has the functions of nourishing blood, nourishing qi, stopping numbness, and clearing collaterals. It has received extensive attention from the medical community. After years of research, scholars at home and abroad have extracted the medicinal component monomers of Paeonia lactiflora, mainly a group of glycosides, including paeoniflorin, hydroxypaeoniflorin, paeoniflorin, paeoniflorin, and benzoyl paeoniflorin. Collectively referred to as total glucosides of peony (TGP), in which paeoniflorin accounts for more than 85% of the total glycosides, it is the main active ingredient of peony.

 The main components of total paeony glycosides (TGP) are: paeoniflorin, hydroxy paeoniflorin, benzoyl paeoniflorin, paeonilactone and paeoniflorin;

 Appearance: light yellow-brown powder;

 Taste: slightly bitter and sour;

 : 10% solution pH 6. 2-6. 8;

Absorption: E _lcm 1% = 165-185;

Optically active ^{_{(powder): [a] D 20 -}} 13-14 (C = 5.2);

 Solubility: with hygroscopicity; soluble in water, ethanol and ethyl acetate; slightly soluble in ethanol and chloroform; clinical role: Only when the mixture is approved by the State Drug Administration for rheumatoid arthritis.

 Generally, the total glycosides of paeony (hereinafter referred to as TGP) are extracted from the stems of paeony, and the preparation method is as follows:

 Step 1: 200 ml of 95% ethanol was added to about 100 grams of peony, and the water bath was heated to reflux for 1 hour, cooled and filtered, and the solution was recovered. The residue was washed twice with 95% ethanol, the washing solution was mixed with the aforementioned alcohol solution, and the water bath was mixed with alcohol. Liquid to obtain about 15 ml of concentrated extract (may also be appropriately dried).

Step 2: Adjust the acid form to pH 5. 9-6. 2 with dilute lye, and extract the obtained concentrated alcohol extract three times with about 30 ml of ethyl acetate (all about 90 ml). The ester extract was concentrated in a water bath to a density of 1.5 g / ml to obtain 6.0 g of a creamy extract (yield: 4-8%). Drying in a drying box (pressure: 15 sides Hg, At a temperature of 95-10 (TC), about 3.0 grams of TGP powder was obtained.

 Paeonia lactiflora (dry) contains about 60-70% carbohydrates, 3-8% TGP and many other substances, including beta-sitosterol, aromatic carboxylic acids, tannins, volatile oils, etc. The above process can effectively extract most of the relatively pure TGP from natural raw materials.

About 10 g of solid matter was extracted from 100 g of white peony with alcohol (step 1) (10 g ± 1.0 g). Table 1: Preparation of TGP: Step 1

After neutralization (0.1 mol / L NaHC0 ₃ ) and ethyl acetate extraction, about 3.0 g of solid matter was obtained, that is, TGP product powder.

 TGP capsules are obtained by filling the TGP powder into capsules, each capsule is about 300mg (excluding any excipients or excipients).

Table 2: TGP preparation: contents after step 2

 The quality and weight of the TGP product obtained are described as:

 Name of block drug: Total glucosides of paeony (TGP)

 Main ingredients: Paeoniflorin, hydroxypaeoniflorin, benzoic acid paeoniflorin, peony lactone and paeoniflorin, other ingredients: hydrocarbons: 7-10% of total weight;

 Tannin: 5-7% of the total weight;

 Appearance: light yellow-brown powder;

 Flavor: slightly bitter and sour

 k .: 10% solution H6.2-6.8

Absorption: E _lcm 1% = 165-185

Optical rotation (powder): [a] _D ²⁰ -13-14 (C = 5.2)

 Solubility: With hygroscopicity; soluble in water, ethanol and ethyl acetate; slightly soluble in ethanol and chloroform. Materials and reagents needed for production:

1. Radic Paeoniae Alba: The crude medicinal material used in TGP products is derived from Luzhou, China. The implementation standard is: Chinese Pharmacopoeia Vol. 1 (1990 edition) P85. 2. The purity of chemical reagents used in the product is industrial grade:

 95% ethanol ethyl acetate sodium bisulfate

 3. The water used for production is pure water without pollution.

 The total glucosides of paeony can be made into decoctions, mixtures, syrups, flow extracts, extracts, decoctions, liquors, tinctures, powders, granules, pills, tablets, etc. Pharmacy, injection and other dosage forms described in pharmacy.

 At present, total glucosides of paeony have been used as a therapeutic agent for treating RA (rheumatoid arthritis). Summary of the Invention

 The purpose of the present invention is to provide a new use of total glucosides of paeony, that is, a new application in pharmaceuticals.

 In fact, the present invention relates to the use of total glucosides of paeony as a medicine for treating or preventing primary xerostomia.

 The invention relates to the application of total glucosides of paeony as a medicine for treating or preventing Behcet's disease.

 The invention relates to the application of total glucosides of paeony as a medicine for treating or preventing pulmonary interstitial fibrosis disease. The invention relates to the application of total glucosides of paeony as a medicine for treating or preventing fibromyalgia syndrome.

 The invention relates to the application of total glucosides of paeony as a medicine for treating or preventing ankylosing spondylitis. The invention relates to the application of total glucosides of paeony as a medicine for treating or preventing liver fibrosis disease.

 The invention relates to the application of total glucosides of paeony as a medicine for treating or preventing systemic lupus erythematosus disease. In the specific application of the present invention, a medicinal composition composed of components consisting of an effective amount of paeoniflorin, peony lactone, hydroxy paeoniflorin, benzoi paeoniflorin, and a pharmaceutically acceptable carrier is used.

 The pharmaceutical composition is composed of the components composed of the ingredients and a pharmaceutically acceptable carrier. For the purposes of the present invention "pharmaceutically acceptable carrier" means any standard pharmaceutical carrier. Examples of suitable carriers are well known to those skilled in the art, and may include (but are not limited to, the substances) any standard pharmaceutical carrier, such as a phosphate buffer and any wetting agent. Additional carriers may include additives for tablets, granules, capsules and the like, 'typically such carriers include excipients such as starch, milk, sugar, defined forms of clay, gelatin, stearic acid and Its salts (including magnesium stearate, calcium stearate), talc, vegetable fat or oil, gum, glycerin or other known excipients. Such carriers may also include aromatic and color additives or other ingredients, and compositions comprising the carrier may be formulated by known convenient methods.

In order to better understand the present invention, the clinical research report and results of total glucosides of paeony Demonstrate its new use in the pharmaceutical field.

 First, the application of total glucosides of paeony in the treatment of primary Sjogren's syndrome

 Primary Sjogren's syndrome (pSS) is a chronic systemic autoimmune disease that manifests as target organ damage caused by the infiltration of lymphocytes and plasma cells into the target organ. In addition to the lacrimal gland and salivary gland, it can also affect kidneys, lungs, liver, and other internal organs, as well as blood, joints, and skin. Interstitial fibrosis and autoimmune cirrhosis often occur in advanced stages. The incidence rate in China is 0.77%, which is the most common disease in chronic rheumatism.

 The main treatment methods for pSS include the use of immunosuppressive agents or glucocorticoids, and plasma exchange, but the former increases the incidence of tumors, hyperlipidemia, secondary diabetes, and osteoporosis in patients, and the latter is costly and Prone to secondary B-cell hyperfunction and aggravate the condition. There is currently no ideal treatment for pSS. Therefore, finding and discovering safe and effective treatments is far-reaching.

 This study compared the control group (single use of hormones) to observe the changes in symptoms, glandular secretion function, and serum immunological parameters of patients before and after treatment. The clinical efficacy of total glucosides of paeony in the treatment of Sjogren's syndrome was analyzed.

 (A), materials and methods

 1. Case selection ''

A total of 63 eligible subjects were included in this clinical study and all met the 1992 European diagnostic criteria (see 2). Including ⁷ males, ⁵⁶ females, aged 48-65 years old. The average age was 53.5 years, the course of disease was 11-34 months, and the average course was 15. August.

 2. Diagnostic criteria (1992 European Standard)

 (1) Have dry eyes or sandy eyes for more than 3 months, or use artificial tears more than 3 times a day. Any one of them is positive.

 (2) Have xerostomia for more than 3 months, or use water when taking dry food, or have persistent and persistent parotid enlargement. Any one of them is positive.

(3) Filter paper test <5mm / 5 minutes or corneal staining index> 4 was positive.

(4) The mononuclear cell infiltrates of the lower lip mucosa biopsy> 1 / 4mm ² were positive.

 (5) mti f salivary gland isotope scan, any one of saliva flow rate is positive.

(6) Serum anti-SSA and anti-SSB antibodies are positive.

Those who have at least 4 of the above 6 items and exclude another connective tissue disease, lymphoma, AIDS Disease, sarcoidosis, and graft-versus-host disease can be diagnosed as primary Sjogren's syndrome. A certain positive connective tissue disease has both (1) or (2) above, and the other two positives (3), (4), (5) are diagnosed as secondary Sjogren's syndrome.

 3. Inclusion criteria: Patients diagnosed with primary Sjogren's syndrome with reference to the diagnostic criteria will voluntarily make all necessary tests to help judge patients with curative effects.

 4. Exclusion criteria

 One of the following cases is an unqualified case and cannot be selected.

 (1) Pregnant or lactating women.

 (2) Patients with severe primary diseases such as cardiovascular, liver, hematopoietic system.

 (3) Those who do not meet the inclusion criteria, fail to take the drug as prescribed, and cannot judge the efficacy or incomplete data, which affect the efficacy or safety.

 5. Elimination criteria

 There were no adverse reactions during the medication, but the treatment was discontinued due to other unforeseen reasons. Those who had to stop medication due to severe adverse drug reactions. In this case, the patients should be excluded from the statistics at the end of the trial and the reasons should be analyzed.

 6. Research methods

 (1) Grouping

 They were randomly divided into treatment group of 33 people and control group of 30 people. There was no significant difference in gender composition, age, and duration of disease between the two groups (P> 0.05, Table 1). There was no significant difference in tear secretion and saliva flow rate between the two groups of patients (P> 0.05, Table 2). There was no significant difference in the positive rates of ANA, anti-SA, anti-SA, and RF, and the levels of IgG, IgA, and gamma globulin in the two groups of patients (P> 0.05, Table 3).

 Two groups of patients' gender composition, age, course of disease

 Tear secretion and saliva flow rate in the two groups of patients

Number of cases with tear secretion (abnormal rate) Saliva flow rate m / mg. 2min Treatment group 33 100% 917 ± 150 Control group 30 100% 907 ± 168 Table 3 Comparison of ANA, anti-SSA, anti-SSB, RF positive rates, and IgG, IgA, and protein levels in the two groups of patients

 (2) Method of medication

 The treatment group took the total glucosides of Paeonia lactiflora 3 times a day, 2 tablets (0.6g) each time, and treated for 6 months. The control group took prednisone 30 mg / d daily and gradually reduced the dose to 10 mg / d.

 (3) Main observation indicators

 ① Subjective symptoms of the patient, such as dry mouth and dry eyes.

 ② Functional indicators, such as: tear secretion and saliva flow rate.

 ③ serum blood indicators, such as: IgG, IgA, gamma globulin, ESR.

 ④No J¾ indicators, such as: ALT, AST, blood cell counting package ^ working cells, white blood cells, platelets. (4) Criteria for determining efficacy

 ① Significant effect: Dry eyes and dry mouth disappeared, joint swelling disappeared, erythrocyte sedimentation decreased to normal range, and albumin globulin ratio was normal.

 ②Effective: Dry eyes and dry mouth are relieved, joint swelling and pain «, erythrocyte sedimentation globulin value decreases. ③ Ineffective: Those who have not improved or deteriorated in clinical and laboratory tests.

 7. Statistical processing

The measurement data are tested and the count data are tested by X ^{2. All} statistics are completed by SPSS 10. 0 statistical software.

 (B) Results

 1.The clinical efficacy is shown in Table 4:

Table ⁴ illustrates the overall efficiency of the treatment was ^92%, no significant difference compared with the control group, indicating TGP on pSS with confirmed efficacy. 2. Glandular secretion changes are shown in Table 5:

 Table 5 shows that the patients' tear and saliva secretion after 3 months of treatment were significantly improved compared to before treatment. Compared with the control group at 3 months and 6 months of treatment, the above two indicators have no significant difference, indicating that the total glucosides of paeony and the low-dose hormone therapy are equivalent.

 3. See Table 6 for serum immunological indicators:

 Table 6 shows that after 6 months of treatment, the levels of IgG, IgA, and gamma globulin in the patients decreased significantly, and the ESR, which reflects the disease activity, was significantly lower than before treatment. This shows that the total glucosides of paeony can effectively reduce the level of autoantibodies and inhibit the autoimmune response of pSS.

 4. Observation of liver adverse reactions, see Table 7.

 Table 7 Comparison of liver function before and after treatment in patients in the treatment group

 Table 7 shows that after 6 months of treatment, the patient did not have liver damage, but the levels of AST and ALT decreased compared to before treatment, indicating that the total glucosides of paeony not only have no toxic side effects on the liver, but also have a protective effect on the liver.

 5. Observation of adverse blood reactions, see Table 8:

-Group RBC (x 10 ¹² ) Platelet (x lO ⁹ )

 3 months 4.8 ± 1 · 2 4.3 ± 1.1 218 ± 78 treatment group

 6 months 4.6 ± 0 · 8 3.8 ± 1.2 233 ± 87

3 months 3.9 ± 0.7 3.5 ± 1.5 243 ± 112 control group

6 months 3.2 ± 0.5 3.2 ± 0.8 231 ± 102 Table 8 shows that there was no significant decrease in RBC, WBC, and platelets in patients treated for 3 months and 6 months, indicating that the total glucosides of paeony had no significant hematological side effects. In contrast, some patients in the control group experienced a decrease in WBC.

 6. Other adverse reactions: Some patients have diarrhea, but they are milder and can be tolerated.

 (C) Discussion and conclusion

 After research, it was found that the application of the total glucosides of paeonia lactiflora (paeony glucosides) to patients with primary Sjogren's syndrome (3 times a day, 0.6 g each time) can significantly improve the tear of patients with primary Sjogren's syndrome And saliva secretion, reduce the levels of IgG, IgA and gamma globulin in the patient's blood and inhibit disease activity. The effective rate at 3 months was 78% ii5ij, and the effective rate at 6 months was ¾ ^ j 92%. And can improve the liver function of patients.

The main pathological changes of Sjogren's syndrome are a large number of abnormally increased immunoglobulins in the blood, humoral immune abnormalities, and hyperglobulinemia increase blood viscosity, leading to circulatory disorders and damage to multiple system organs. According to the pharmacological studies of total glucosides of paeony, total paeony can inhibit the proliferation of B cells and reduce the secretion of autoantibodies. Moreover, it can reduce the levels of inflammatory cytokines TNFou IL-2, inflammatory mediators PGE ₂ , LTB ₄ , and oxygen free radicals. These pharmacological effects allow total glucosides of paeony to inhibit abnormally hyperhumoral immunity in patients with Sjogren's syndrome, reduce the attack of autoantibodies on normal tissues and damage to the body by autoimmune inflammation, thereby treating patients with primary Sjogren's syndrome effect.

 The above-mentioned research shows that the total aroma of Paeonia lactiflora has a definitive effect on primary dryness syndrome. At the same time, in terms of the safety of the drug, total glucosides of paeony have no toxic and side effects in the blood and liver, and also have a protective effect on liver function damage caused by pSS itself. Application of total glucosides of paeony in the treatment of Behcet's disease

Bechet, s disease is a chronic vascular inflammatory disease involving multiple organs. It is mainly manifested as recurrent oral, external genital ulcers and iritis. It can be accompanied by arthritis, vasculitis and nervous system. Damage, a small number of patients can also appear interstitial pneumonia, peritonitis, myocarditis and digestive system complications, the disease is most commonly distributed in the eastern Mediterranean and Far East countries, the highest incidence in Turkey is 3. 7%, China is about 4 / 100,000 . The etiology of Behcet's disease is diverse and related to heredity, infection, immune process and endothelial dysfunction; the pathogenesis is not clear, and it is related to immune abnormalities, hyperneutrophil dysfunction, and secondary vascular endothelial cell damage and function Disorders are related. Systemic treatment should be used when the disease has severe skin and mucosal damage and systemic damage. However, there is no unified standard scheme so far. Therapeutic drugs include corticosteroids, azathioprine, cyclosporine A, sulfasalazine, etc., but these medicine There are many side effects of the substance, and it is usually unable to be applied for a long time. Moreover, the patient is highly heterogeneous and has various clinical manifestations. The above treatments often fail to achieve the desired effect.

 The patients were treated with oral paeony total glucoside preparations for 6 months, and then treated with glucocorticoids. The changes in symptoms, signs, and immunological indicators before and after treatment were observed separately. The aim was to analyze the clinical efficacy of total glucosides of paeony in the treatment of Behcet's disease.

 (A), materials and methods

 Data selection

 A total of 50 qualified subjects in this clinical study, all meeting the 1989 international standards, including 23 males and 27 females, with an average age of 35 years, with a course of June to 24 months, with an average course of 12 ± 6.1 months.

2. Diagnostic criteria ⁽¹⁹⁸⁹ international standard)

 (1) Repeated oral ulcers.

 (2) Repeated genital ulcers.

 (3) Ocular lesions: anterior and / or posterior uveitis.

 (4) Skin lesions: Nodular erythema-like lesions, pseudopiliotitis, acne-like rash.

 (5) Acupuncture test was positive.

 Anyone who has "recurrent oral ulcer" as described in (1) above and is accompanied by any two or more of the latter four items can be diagnosed as the disease.

 3. Inclusion criteria

 Patients diagnosed with Behcet's disease by referring to the diagnostic criteria and voluntarily conducting all necessary examinations are helpful for patients who have judged the curative effect.

 4. Exclusion criteria

 One of the following cases is an unqualified case and cannot be selected.

 (1) Pregnant or lactating women.

 (2) Patients with severe primary diseases such as cardiovascular, liver, hematopoietic system.

 (3) Those who do not meet the inclusion criteria, fail to take the drug as prescribed, and cannot judge the efficacy or incomplete data, which affect the efficacy or safety.

 5. Elimination criteria

Patients who have no adverse reactions during medication, but who have discontinued treatment due to other unforeseen reasons; Those who must stop medication due to serious adverse drug reactions, in which case the disease should be excluded when statistics are completed at the end of the trial Example, and analyze its cause.

 6. Research methods

 (1) Grouping

They were randomly divided into 25 treatment groups and 25 control groups. Two groups of patients gender, age, duration no significant difference (P> 0.0 ^5, Table 1). There were no significant differences in white blood cell count, ESR, and C-reactive protein between the two groups of patients (P> 0.05, Table 2). There was no significant difference in serum IgG, IgA, IgM, and circulating complex levels between the two groups of patients (P> Q.05, Table 3).

 Table 1 Gender composition, age, and course of disease of the two groups of patients

WBC count, ESR, C-reactive protein

 Comparison of serum IgG, IgA, IgM, and circulating complex levels between the two groups of patients

 (2) Method of medication

 In the treatment group, the total glucosides of paeony glycosides were treated 3 times a day, 2 tablets (0.6g) each time, and treated for 6 months. The control group took prednisone 30 mg / d daily and gradually reduced the dose to 10 mg / d.

 (3) Main observation indicators

 ① Symptoms and signs, such as ulcer healing.

 ②Laboratory indicators, such as: IgG, IgA, IgM, ESR, CRP, circulating immune complex, WBC

③ indicators of adverse reactions, such as: ALT, AST, infection rate, incidence of hypertension, blood sugar.

 (4) Efficacy criteria

① Significant effect: Symptoms and signs disappeared, and within a year, there was light recovery, and laboratory tests were normal. ②Effective: Symptoms and signs improved, relapse time prolonged, and laboratory tests were normal.

③ Invalid: No improvement in symptoms and signs, and most of the actual-risk tests are abnormal.

 7. Statistical processing

The measurement data are tested and the count data are tested by X ^{2. All} statistics are completed by SPSS 10. 0 statistical software.

 (B) Results

 1. The clinical efficacy is shown in Table 4.

Table 4 Comparison of clinical efficacy between the two groups

 Table 4 shows that the total treatment efficiency is 84%, and there is no significant difference compared with the control group, indicating that the total glucosides of paeony have an exact effect on Behcet's disease.

2.The change of disease activity before and after treatment is shown in Table 5:

 Table 5 The white blood cell count, erythrocyte sedimentation rate, and C-reactive protein were significantly reduced after treatment, p <0.05.

3. Changes in serum IgG, I _g A, I _g M, and circulating complexes before and after treatment are shown in Table 6:

 Table 6 shows that the serum IgG and IgA of the patients were significantly reduced after treatment, p <0.05.

4. Observation of adverse reactions, see Table 7:

Table 7 shows that after 6 months of treatment, the patient did not appear liver damage, but the levels of AST and ALT were lower than before treatment, indicating that it can have no toxic side effects on the liver and may have a protective effect on the liver. Moreover, the incidence of hypertension, infection rate, and incidence of hyperglycemia were lower than those in the control group, and the differences were significant, p <0.05. 5. Other adverse reactions: Some patients have diarrhea, but they are milder and can be tolerated.

 (Three), conclusion

According to the pharmacological studies of the total glucosides of paeony and the clinical studies mentioned above, 'the total glucosides of paeony can inhibit the proliferation of B cells and reduce the secretion of autoantibodies. And can reduce blood _{TNFcu IL-2, 2, LTB} 4, and the level of oxygen radicals inflammatory mediators PGE inflammatory cytokines. These pharmacological effects allow total glucosides of paeony to inhibit abnormally hyperhumoral immunity in patients with Behcet's disease, reduce the attack of autoantibodies on normal tissues, and damage to the body from autoimmune inflammation, thereby playing a role in treating Behcet's disease.

 The above study used Paeonia lactiflora papillae (Paeba glucosides) in the treatment of Behcet's disease, and found that it can effectively control the disease activity, P ^ patients' blood sedimentation, immunoglobulin levels, and promote ulcer healing, the efficacy is comparable to glucocorticoids However, it can reduce the amount of hormones, and reduce the incidence of elevated blood sugar, hypertension and peptic ulcers. It is an ideal drug choice for Behcet maintenance therapy. Application of total glucosides of paeony in the treatment of pulmonary interstitial fibrosis

 Pulmonary interstitial fibrosis includes idiopathic pulmonary interstitial fibrosis and secondary pulmonary interstitial fibrosis. Its pathological feature is fibrous hyperplasia of the interstitial lung, which reduces lung compliance and causes respiratory dysfunction. The pathogenesis of idiopathic pulmonary interstitial fibrosis is unknown and may be related to immunity. Studies have found that immune complexes can be detected in alveolar lavage fluid from patients with idiopathic pulmonary interstitial fibrosis, and the immune complexes are injected into healthy lung It can also induce pulmonary fibrosis. Secondary pulmonary interstitial fibrosis can be secondary to a variety of obstructive pulmonary diseases and autoimmune diseases, especially Sjogren's syndrome, with pulmonary interstitial fibrosis occurring in 60-70% of patients at advanced stages.

 At present, adrenocortical hormone is still the first choice for the treatment of pulmonary interstitial fibrosis. However, hormone therapy only has a certain effect on the stage of alveolitis, and it cannot completely control the development of the disease. Treatment is often terminated due to long-term use of intolerable side effects.

 The patients were treated with oral paeony total glucoside preparations for 6 months, and then treated with glucocorticoids. Observe the clinical symptoms and changes in lung function before and after treatment in the two groups of patients. The aim is to analyze the clinical efficacy of total glucosides of paeony in the treatment of pulmonary interstitial fibrosis.

 (A), materials and methods

 Case selection

Forty patients with primary Sjogren's syndrome secondary to pulmonary interstitial fibrosis were selected. X-rays confirmed the presence of pulmonary interstitial fibrosis. Pulmonary function tests showed varying degrees of pulmonary dysfunction, including 5 males and 35 females. Cases, aged 36-64 years, with an average of 45.4 years, with a course of 6-120 months, with an average of 28.2 months. 2. Diagnostic criteria ⁽¹⁹⁹² European standard)

 (1) Have a sense of astringency in the eyes for more than 3 months, or a silicon-child feeling, or use artificial tears more than 3 times a day. Any one of them is positive.

 (2) Xerostomia for more than 3 months, or with water when taking dry food, or repeated parotid enlargement. Any one of them is positive.

 (3) The filter paper test <5 wakes / 5 minutes or corneal staining index> 4 is positive.

(4) The mononuclear cell infiltrates of the lower lip mucosa biopsy> 1 / 4mm ² were positive.

 (5) Cheek shadow, salivary gland isotope scan, any one of salivary flow rate is positive.

 (6) Positive anti-SSA and anti-SSB antibodies.

Those with at least 4 of the above 6 items and excluding another connective tissue disease, lymphoma, AIDS, sarcoidosis, and graft-versus-host disease can be diagnosed as primary Sjogren's syndrome. A certain positive connective tissue disease has both (1) or ( ² ) above, and the other two positives (3), (4), (5) are diagnosed as secondary xerostomia.

 3. Inclusion criteria

 (1) Meet the diagnostic criteria for primary xerostomia syndrome.

 (2) X-ray confirmed the presence of pulmonary interstitial fibrosis.

 (3) Stop using other anti-rheumatic drugs such as non-steroidal anti-inflammatory drugs, corticosteroids, immunosuppressive drugs and disease-modifying drugs for at least 2 months.

 (4) Those who are willing to receive 24 weeks of treatment and inspection.

 4. Exclusion criteria

 (1) Pregnant or lactating women.

 (2) Patients with severe cardiovascular, liver, kidney and system diseases and mental illness.

 5. Elimination criteria

 There were no adverse reactions during the medication, but the treatment was discontinued due to other unforeseen reasons. Those who had to stop medication due to severe adverse drug reactions. In this case, the patients should be excluded from the statistics at the end of the trial and the reasons should be analyzed.

 6. Research method

 (1) Grouping

Randomly divided into treatment group of 20 people, control group of 20 people. Two groups of patients' gender composition, age, course of disease No significant difference (P> 0.05, Table 1). There was no significant difference in lung function between the two groups (P> 0.05, Table 2). Table 1 Gender composition, age, and duration of disease in the two groups

 (2) Method of medication

 In the treatment group, the total glucosides of paeony was administered orally 3 times a day, 600 mg each time.

Group control group was given prednisone per day, 30mg / d, the gradual reduction of 10 mg / d _c the two groups of patients during treatment with non-steroidal anti-inflammatory drug plus pain significantly after 6 months of treatment evaluated.

(3) Efficacy criteria

 Healed: clinical symptoms ^! Husband and wife are disappearing, lung function and lung HRCT'l ~ E are constant, and their activities are the same as normal people. Improvement: Forced vital capacity (FVC) total lung (TLC) increased by 10%, and diffuse (DLC0) increased> 20%. Stable: clinical symptoms, stable signs, lung function FVC, TLC increase <10%, decrease <15%, DLC0 change range (rise or decrease) <20%, pulmonary HRCT showed alveolar inflammation absorption or no change, fibrosis No change.

 Deterioration: The standard is FVC, which decreases by> 15%, and DLC0 decreases by> 20%.

 (4) Observation indicators

 a. Pulmonary function, including: forced vital capacity (FVC), total lung volume (TLC), unit alveolar gas diffusion volume (DLC0).

 b. Liver and kidney function, blood routine.

 7. Statistical processing

The measurement data is t, and the count data is X ² inspection. All statistics are completed by SPSS 10.0 statistical software. (B) Results

1. The clinical efficacy is shown in Table 3:

 Table 3 shows that the total treatment efficiency is 70%, and the cure rate of the total glucoside glycoside treatment group is significantly higher than that of the control group (p <0.01). There is no significant difference between the improvement rate and the stability rate of the control group; there is no case in the treatment group. Worsened, compared with three cases of malignancy in the control group4.

 2. Changes in lung function before and after treatment are shown in Table 4:

 Table 4 shows that FVC and TLC showed slight improvement but no significant difference after treatment in the treatment group. The unit alveolar gas diffusion volume was significantly improved compared with that before treatment (p <0.05). There was no significant change in the above three indicators in the control group.

 3. The incidence of adverse reactions in the two groups of patients before and after treatment%

table 5

 Table 5 shows that the incidence of adverse reactions in the gastrointestinal tract, liver function, and blood system of the total glucoside glycoside treatment group was significantly lower than that of the control group (p <0.05).

 4. Other adverse reactions: Some patients have diarrhea, which is milder and can be tolerated.

 (Three), conclusion

In this study, the total glucosides of paeony were used to treat 40 patients with primary pulmonary interstitial fibrosis secondary to Sjogren's syndrome. It was found that it can effectively control disease activity and improve lung function. The effect is better than prednisone, and the side effects are significantly less than Hormones are an ideal drug for treating pulmonary interstitial fibrosis. Application of total glucosides of paeony in the treatment of fibromyalgia syndrome

 Fibromyal syndrome (FMS) is one of the most common rheumatic diseases. FMS accounts for approximately 12.5% of rheumatology clinics, with an incidence rate of 3.4% in females and 0.5% in males, and the age of onset is 30-60 years. Its characteristic symptom is diffuse soft tissue pain. At present, the cause of FMS is unknown, and research has found that it is related to immune disorder, abnormal neurotransmitter secretion, and sleep disorders. FMS patients had elevated serum IL-2 levels, increased CD4 + lymphocytes, and increased CD4 + / CD8 + ratios. It may also be related to the abnormal secretion of neurotransmitters. The serotonin content in the cerebral fluid of patients with FMS is significantly reduced, the content of substance P is increased, and the level of free tryptophan in the serum is reduced; At 24 hours, serum free glucocorticoid levels were reduced, pituitary released ACTH, and the adrenal ACTH response was decreased.

 At present, there are no specific drugs for the treatment of FMS, and sedatives and non-steroidal anti-inflammatory drugs are often used to control symptoms. These drugs do not fundamentally solve the patient's problems, and long-term use can cause dependence and side effects in the gastrointestinal tract.

 The patients were treated with oral total glucoside preparation of paeony for 6 months and compared with amitriptyline treatment. The changes in symptoms, signs, and immunological indicators before and after treatment were observed separately. The aim was to analyze the clinical efficacy of total glucosides of paeony in the treatment of fibromyalgia.

 (A), materials and methods

 Case selection

 A total of 50 eligible subjects in this study, all meeting the following diagnostic criteria, 4 males and 46 females, aged 19-56 years, mean 30. 4 years old, duration of disease 3-60 months, average 12. 2 months There was no significant difference between the two groups of patients in age, gender, course of disease, and disease activity.

 Diagnostic criteria

 (1) A history of diffuse pain throughout the body, including the left and right scapular and pelvic girdles of the body, the upper and lower parts of the waist, and the central axis bones (neck push or front chest or lower back), with a history of at least 3 months.

(2) Among the 18 tenderness points in the whole body, at least 11 or more thumb pressures of 4 kg / cm ² tenderness (+), the 9 pairs (18) tenderness points are: occipital bone, lower neck, trapezius Part, superior psoas muscle part, second rib part, humerus epicondyle part, hip, trochanter part, knee part.

 3. Inclusion criteria

① Meet the diagnostic criteria. ② has active lesions.

 ③ Stop using other anti-rheumatic drugs such as non-steroidal anti-inflammatory drugs, corticosteroids, immunosuppressants and disease-modifying drugs for at least 2 months.

 ④ Those who are willing to receive treatment and review for 24 weeks.

 4. Exclusion criteria

 ① Pregnant or lactating women.

 ② Inactive patients.

 ③ Patients with severe cardiovascular, liver, kidney and hematopoietic diseases and mental illness.

 5. Elimination criteria

 There were no adverse reactions during the medication, but the treatment was discontinued due to other unforeseen reasons. Those who had to stop medication due to severe adverse drug reactions. In this case, the patients should be excluded from the statistics at the end of the trial and the reasons should be analyzed.

 6. Research methods

 (1) Grouping

 They were randomly divided into 25 treatment groups and 25 control groups. There was no significant difference between the two groups of patients in terms of gender composition, age, and course score (P> 0.05, Table 1).

 Table 1 Gender composition, age, and course of disease of the two groups of patients

 (2) Method of medication

 The treatment group was taken orally with the total glucosides of paeonia lactiflora, 600 mg 3 times a day.

 The control group, amitriptyline, was taken orally before bedtime, and severe pain was added to nonsteroidal anti-inflammatory drugs.

 The efficacy was evaluated after 6 months of treatment.

 (3) Efficacy criteria

 Significant effect: The patient's self-assessment and doctor's evaluation significantly improved the condition, significantly improved sleep, and no significant pain.

Effective: Patient's self-assessment and doctor's evaluation of improved condition, improved sleep and pain. Ineffective: The patient's own assessment and doctor's evaluation showed no improvement or no significant improvement.

 (4) Observation indicators

 a. Clinical indicators: Morning stiffness, sleep, pain and tenderness.

 b. Laboratory inspection index: IL-2.

 c liver and kidney function, blood routine.

 7. Statistical processing

The measurement data is tested by ί, the count data is tested by X ² and all statistics are completed by SPSS 10. 0 statistical software.

 (B) Results

1.The clinical efficacy is shown in Table 2:

 Table 2 shows that the total treatment efficiency is 88%, the significant efficiency is significantly higher than the control group (p <0.05), and the ineffective rate is significantly lower than the control group (p <0.05).

2.The changes of symptoms before and after treatment are shown in Table 3:

 Table 3 shows that the pain improvement rate, morning stiffness improvement, and sleep improvement rate of the total glucoside glycoside treatment group were significantly higher than those of the control group (ρ <0.05).

 3. See Table 4 for the changes of patients' signs before and after treatment.

 Table 4 Changes in tenderness points of the two groups of patients before and after treatment

 Table 4 shows that the average tenderness point of the treatment group after treatment was significantly lower than that of the control group (ρ <0.05), and the ability of Paeonia lactiflora to relieve pain was better than traditional treatment.

4. The changes of serum IL-2 in the two groups of patients before and after treatment are shown in Table 5. Table 5 Changes in serum IL-2 concentration in the two groups of patients before and after treatment

 Table 5 shows that the serum IL-2 concentration in the treatment group was significantly lower than that in the control group after treatment (p <Q. 05).

 5. The incidence of adverse reactions in the two groups of patients before and after treatment is shown in Table 6.

Table 6 The incidence of adverse reactions in the two groups before and after treatment

 Table 6 shows that the incidence of adverse reactions in the gastrointestinal tract, liver function, and blood system of the total glucoside glycoside treatment group was significantly lower than that of the control group (ρ <0.05).

 6. Other adverse reactions: Some patients have diarrhea, which is milder and can be tolerated.

 (Three), conclusion

 According to the pharmacological studies of total glucosides of paeony and the above studies, total paeony can reduce the level of IL-2 and regulate the differentiation of T cells; it can also regulate the function of hypothalamus-pituitary-adrenergic axis; it can also prolong slow wave sleep Phases, improve sleep status; and have anti-inflammatory and analgesic effects. Thereby, the autoimmune response of fibromyalgia syndrome can be suppressed in multiple links, and the symptoms such as endocrine and fatigue can be adjusted.

 This study used total glucosides of paeony to treat fibromyalgia syndrome, and found that it can effectively inhibit autoimmune response, reduce pain and improve sleep. The efficacy is 88%, which is significantly higher than traditional treatment based on amitriptyline, and the side effects Significantly lower than the control group. It shows that the total glucosides of paeony is an ideal medicine for the treatment of fibromyalgia syndrome. V. Application of Paeonia lactiflora in the treatment of ankylosing spondylitis

Ankyloys ing spondyl itis (AS) is a progressive autoimmune disease of unknown cause. The lack of a specific treatment at present is one of the problems that the medical community is concerned about. Its characteristics are Axial joint chronic inflammation, as the disease progresses, may be accompanied by damage to organs such as lungs, heart, kidneys, etc. If not treated in time, it will cause multiple joints and dysfunction, and the incidence of AS is China is about 0.2% -0.

 The basic lesion of AS is apexitis, which occurs at most in the sacral joints, intervertebral discs, thrust ligaments, and Achilles tendon. The initial stage is mainly infiltration of lymphocytes and plasma cells, with a few mononuclear cells, and then bone Destruction and new bone formation, eventually resulting in fibrosis and ossification of the sacroiliac joint bone fusion and spinal nodules. At present, the main drugs for the treatment of AS are mainly non-steroidal anti-inflammatory drugs, disease-modifying drugs (such as sulfasalazine), glucocorticoids, and immunosuppressants. These drugs can control the condition of some patients, but larger doses and long-term use of these drugs often lead to more serious side effects, making treatment difficult to continue.

 The patients were treated with oral total glucoside preparation of paeony for 6 months, and the treatment was compared with salazodine. To observe the changes in symptoms, physical symptoms and serum immunological parameters before and after treatment, and to analyze the clinical efficacy of total glucosides of paeony in the treatment of ankylosing spondylitis.

 (A), materials and methods

 Case selection

 A total of 48 eligible subjects in this study, all meeting the diagnostic criteria revised by the American Rheumatological Association in 1984, 44 males and 4 females, aged 14-41 years old, average 20. 4 years old, duration of 6-120 months, On average 18.2 months, there was no significant difference in age, gender, course of disease, and disease activity between the two groups of patients.

 2. Diagnostic criteria (New York ^ Daddy Standard)

 ① The course of lower back pain is at least 3 months. The pain improves with the activity, but the rest does not decrease.

 ② Lumbar push has limited movement in the forward, backward, and lateral flexion directions.

 ③ Thoracic activity is less than the normal value of the same age and gender.

 ④ X-ray examination: Ankylosing spondylitis can be diagnosed by bilateral iliac arthritis II-IV changes or III-IV changes, and adding any one of the above 1-3 respectively.

 3. Inclusion criteria

 ① Meet the diagnostic criteria.

 ②Age 12-45 years old.

 ③ has active lesions.

 ④ Stop using other anti-rheumatic drugs such as non-steroidal anti-inflammatory drugs, corticosteroids, immunosuppressive agents and disease-modifying drugs for at least 1 month.

⑤ Those who are willing to receive treatment and inspection for 24 weeks. 4. Exclusion criteria

 ① Those who are younger than 12 years old or older than 45 years old, pregnant or lactating women.

 ② Inactive patients.

 ③ Patients with severe cardiovascular, liver, kidney and hematopoietic diseases and mental illness.

 5. Elimination criteria

 There were no adverse reactions during the medication, but the treatment was discontinued due to other unforeseen reasons. Those who had to stop medication due to severe adverse drug reactions. In this case, the patients should be excluded from the statistics at the end of the trial and the reasons should be analyzed.

 6. Research methods

 (1) Grouping

They were randomly divided into 24 groups in the treatment group and 24 in the control group. Two groups of patients gender, age, duration score was no significant difference (P> 0. 0 ^5, Table 1). There was no significant difference in disease activity between the two groups (P> 0.05, Table 2, Table 3).

 Two groups of patients' gender composition, age, course of disease

 Staging of patients in the second group

 Disease activity of two groups of patients (X soil SD)

 (2) Method of medication

The total glucosides of paeony in the treatment group were taken orally, 600 mg 3 times a day. 5g。 Oral sulfasalazine in the control group, 0.5 g 3 times a day.

 Non-steroidal anti-inflammatory drugs were added to the two groups of patients during treatment, and the treatment effect was evaluated after 6 months of treatment.

 (3) Efficacy criteria

 Complete remission: The patient's self-assessment and doctor's evaluation significantly improved the condition, no joint pain and limited movement, laboratory tests were all normal, the overall improvement rate of clinical observation indicators reached more than 80%, and overall function improved.

 Significant progress: The patient's self-assessment and doctor's evaluation of the disease have improved, and the overall improvement rate of clinical indicators is> 60%, and the overall function has improved Π level.

 Progress: The patient's self-assessment and doctor's evaluation of the disease have improved, and the overall improvement rate of clinical indicators is between 30% -00%, and the functional improvement is Grade I. Effectiveness = (completely obvious progress + progress) / total χΐοο ° /. .

 Ineffective: The patient's self-assessment and doctor's evaluation did not improve or the improvement was not obvious, and the clinical index improvement rate was <30%.

 (4) Observation indicators

 a. Clinical indicators: morning stiffness, sacroiliac joint tenderness, ground distance, breast expansion, peripheral joint swelling number, peripheral joint tenderness score and swelling score.

 b. Laboratory indicators: ESR platelets, immunoglobulins, CRP.

 c. Liver and kidney function, blood routine.

 7. Statistical processing

The measurement data are tested and the count data are tested by X ^{2. All} statistics are completed by SPSS 10. 0 statistical software.

 (B) Results

1. The clinical efficacy is shown in Table 4:

Table 4 shows that the total treatment efficiency is ⁹⁰ %, and there is no significant difference compared with the control group, indicating that the total glucosides of paeony have a confirmed effect on AS.

2. The changes of disease activity before and after treatment are shown in Table 5. Disease activity

 Table 5 shows significant improvement after treatment. Morning stiffness, joint swelling, ESR, and CRP were significantly different from those before treatment (<0.01 or p <0.05).

 3. The changes of liver and kidney function in the treatment group and control group before and after treatment are shown in Table 6:

 Table 6 shows that liver function of the paeony total glycoside group was significantly improved after treatment (* p <0.05), and renal function was not decreased. In the control group, AST was significantly higher than before treatment (#p <0. 05).

 4. Changes in blood routine of the treatment group and control group before and after treatment are shown in Table 7:

 Table 7 shows that the Hb, WBC, and platelets of patients in the total glucoside group for 6 months were not significantly lower than before treatment. In the control group, WBC and platelet counts decreased significantly, * p <0.05.

 5. Other adverse reactions: Some patients have diarrhea, which is milder and can be tolerated.

 (Three), conclusion

According to the pharmacological studies of the total glucosides of paeony and the above-mentioned studies, the total glucosides of paeony can inhibit the proliferation of B cells and reduce the secretion of autoantibodies. And can reduce blood inflammatory cytokines TNFa, IL- 1, IL- 2, the inflammatory mediators PGE _2, LTB _4, and the level of oxygen radicals. These pharmacological effects allow total glucosides of paeony to inhibit abnormally hyperhumoral immunity in AS patients, reduce the attack of normal tissues by autoantibodies, and damage to the body by autoimmune inflammation.

The above studies used total glucosides of paeony to treat ankylosing spondylitis, and found that it can effectively control the disease activity, reduce the patient's serum sediment, C-reactive protein, reduce pain and improve joint function. Azathiopyridine is equivalent, but the side effects on the liver and blood system are significantly less than that of sulfasalazine, which proves to be a new drug option for treating ankylosing spondylitis.

 Application of total glucosides of paeony in the treatment of liver fibrosis

 Hepatic fibrosis is an important change in chronic hepatitis B. It is a pathological process from the development of chronic hepatitis to cirrhosis. The development of liver fibrosis is closely related to the progress and prognosis of liver disease. Terminating the disease in the stage of liver fibrosis is the prevention and treatment of The key link in the irreversible development, but there is currently no ideal treatment.

 In this study, the total glucosides of paeony were added on the basis of the original liver-protecting drugs, and compared with the treatment with liver-protecting drugs alone. Observe the clinical symptoms, symptoms, physical symptoms, and changes in hyaluronic acid (HA), mucin (LN), and pre-III collagen (PC III) before and after treatment in the two groups of patients; Clinical efficacy of pulmonary interstitial fibrosis.

 (A), materials and methods

 Case selection

 According to the 1995 Chinese Academy of Infectious Diseases and Parasitic Diseases 'diagnostic criteria for' i hepatitis B (CHB), there were 100 patients, including 65 males and 35 females, with an average of 34.6 ± 16.4 years old. 2. 3 ± 1.9 years.

 2. Diagnostic criteria Chronic hepatitis B (CHB) diagnostic criteria revised in 1995 according to the Chinese Academy of Infectious and Parasitic Diseases.

 3. Inclusion criteria Patients diagnosed with chronic hepatitis B with reference to the diagnostic criteria will voluntarily conduct all necessary examinations, which is helpful for patients who have judged the curative effect.

 4. Exclusion criteria

 One of the following cases is an unqualified case and cannot be selected.

 (1) Pregnant or lactating women.

( ² ) Patients with severe primary diseases such as cardiovascular, liver, hematopoietic system.

 (3) Those who do not meet the inclusion criteria, fail to take the drug as prescribed, and cannot judge the efficacy or incomplete data, which affect the efficacy or safety.

 5. Elimination criteria

There were no adverse reactions during the medication, but the treatment was discontinued due to other unforeseen reasons. Those who had to stop medication due to serious adverse drug reactions. In this case, cases should be excluded when statistics are made at the end of the trial and the reasons should be analyzed. 6. Research methods

 (1) Grouping

 They were randomly divided into 50 test groups and 50 control groups. There were no significant differences in gender composition, age, and duration of disease between the two groups (P> 0.05, Table 1). There was no significant difference in liver function between the two groups (P> 0.05, Table 2). Hepatic fibrosis-related indicators of the two groups of patients were not significantly different from hyaluronic acid (ΗΑ), mucin (LN), and pre-III collagen (PC III) (P> G.05, Table 3).

 Table 1 Gender composition, age, and course of disease of the two groups of patients

Liver function in the first two groups of patients

Table 3 Comparison of the levels of hyaluronic acid (HA), mucin (LN), and pre-type III collagen (PC III) in the two groups of patients before treatment (g / ml) ''

 (2) Method of medication

 Both groups were treated with general liver-protective treatments, such as maggot aspartate and gantelor. The treatment group was treated with baijiongxiangxiangjiao 3 times a day, 2 tablets (0.6g) each time, for 3 months.

 (3) The main idea

 ① liver function indicators, such as: alanine aminotransferase, total bilirubin, albumin, globulin.

② liver fibrosis indicators, such as: hyaluronic acid (HA), mucin (LN), pre-type III (PCIII) 7. Statistical processing

The t-test was used for the measurement data, and the X ² test was used for the count data. All the statistics were completed by SPSS 10. 0 statistical software.

 (B) Results

 1. The liver function changes of the two groups of patients after treatment are shown in Table 4:

 Table 4 shows that the liver function indexes of the patients in the experimental group and the control group were significantly improved compared with those before the treatment after 3 months of treatment. There was no significant difference between the two groups compared with the above four indicators.

 2. The changes of hyaluronic acid (HA), mucin (LN), and pre-III blood type (PC III) in the two groups of patients after treatment are shown in Table 5.

 Table 5 Unit ^ g / ml)

 Table 5 shows that the liver fibrosis index of the patients in the experimental group after 3 months of treatment was significantly improved compared with that before treatment. And better than the control group using only general liver protection treatment, the two groups have significant differences compared to the above three indicators.

 3. Adverse reactions: Some patients have diarrhea, but they are mild and can be tolerated.

 (C) Discussion and conclusion.

Inflammatory necrosis of liver cells during hepatitis is the initiating factor for liver fibrosis. The pharmacological studies TGP glycoside, TGP glucosides can reduce blood inflammatory cytokines _{TNFa, IL-2, 2,} LTB 4, the level of oxygen radicals and inflammatory mediators PGE. These pharmacological effects allow total glucosides of paeony to inhibit inflammation and thus restore liver function and prevent the formation of liver fibrosis.

This study found that the application of total glucosides of paeony in the treatment of liver fibrosis in chronic hepatitis B can significantly improve liver function and inhibit the progress of liver fibrosis without serious adverse reactions. 7. Application of total glucosides of paeony in the treatment of systemic erythema erythematosus

 Systemic lupus erythematosus (SLE) is an autoimmune disease that invades the connective tissues of the whole body. The incidence rate in China is 70 / 100,000. The etiology of SLE is unknown, and it is generally considered to be multifactorial. It is related to genetics, sex hormones, and environmental factors, and is characterized by multi-tubular and multi-system involvement. Most patients have a slow disease course, but they can also start suddenly or become worse. Adrenocortical hormone and immunosuppressive agents are mainly used in the treatment of SLE. Some patients can temporarily control the condition, but large doses and long-term use of these drugs often lead to more serious side effects and often make it difficult to continue treatment.

 In this study, patients were treated with oral total glucoside preparations and treated with glucocorticoid alone. Observe the changes in symptoms, signs, and serum immunological parameters before and after treatment to determine the therapeutic effect and adverse reactions on systemic lupus erythematosus. To analyze the clinical efficacy and safety of total glucosides of paeony in the treatment of SLE.

 (A), materials and methods

 Case selection

 A total of 100 eligible subjects met the diagnostic criteria revised by the American College of Rheumatology in 1982. There were 9 males and 91 females, aged 14-61 years, with an average of 25.4 years, and a course of 3-240 months with an average of 36. month. There were no significant differences in age, gender, disease duration, and disease activity (SLEDAI score) between the two groups.

2. diagnostic criteria (American College of Rheumatology ¹⁹⁸² revised)

 (1) Butterfly erythema.

 (2) Discoid erythema.

 (3) Light sensitive.

 (4) Oral ulcer.

 (5) Arthritis, and 2 or more joints.

 (6) Serositis, including meningitis or pericarditis.

 (7) Renal disease, proteinuria,> 0.5g per day, cast.

 (8) The nervous system is abnormal.

 (9) Hematological abnormalities: hemolysis, increased reticulocytes, decreased blood cells, decreased lymphocytes, and thrombocytopenia.

(10) immunological abnormalities, positive for LE cells, positive for anti-dsDNA antibodies, negative for anti-Sm, The syphilis serum test was false positive.

 (11) Positive anti-nuclear target.

 SLE can be diagnosed if there are more than 4 positive results.

 3. Inclusion criteria

 Patients diagnosed with systemic lupus erythematosus with reference to the diagnostic criteria, and voluntarily make all necessary tests, are helpful for patients who are judged of the efficacy.

 4. Exclusion criteria

 One of the following cases is an unqualified case and cannot be selected.

 (1) Pregnant or lactating women.

 (2) Patients with severe primary diseases such as cardiovascular, liver, hematopoietic system.

 (3) Those who do not meet the inclusion criteria, fail to take the drug as prescribed, and are unable to judge the curative effect or lack of appetite, etc., which affect the curative effect or safety.

 5. Elimination criteria

 There were no adverse reactions during the medication, but the treatment was discontinued due to other unforeseen reasons. Those who had to stop medication due to severe adverse drug reactions. In this case, the patients should be excluded when the statistics are completed at the end of the trial, and the reasons should be analyzed.

 6. Research method

 (1) Grouping

 Randomly divided into treatment group of 50 people, control group of 50 people. There was no significant difference in gender composition, age, and duration of disease between the two groups (P> 0.05, Table 1). There was no significant difference in SLEDAI scores between the two groups of patients (P> 0.05, Table 2).

 Table 1 Gender composition, age, and course of disease of the two groups of patients

 Two groups of patients SLEDAI evaluation

 SLEDAI

<9 9-19> 20 treatment group 8% 70% 22% control group 10% 66% 24% (2) Method of medication

Those in the treatment group who did not use hormones before treatment received oral administration of total paeoniflorin capsules 3 times a day, 600mg each time _; those who were taking hormones at the time of treatment, continued to take the original doses, while giving total paeoniflorin Nang plastic, use the same before and after taking three weeks decreasing hormone, a daily dose of 30mg or more, weekly reduction 5mg, ^<3 00mg decremented by ⁵ mg per week.

 In the control group, prednisone was orally administered at 30 to 60 mg per day. After the effect was significantly reduced, the dose was reduced. The decreasing method was the same as that in the treatment group, and the last 10 to 15 mg was maintained.

 During the treatment of the two groups, calcium and vitamins were added, and the curative effect was evaluated after 6 months of treatment. (3) Efficacy evaluation standard (1993 SLE Efficacy Standard)

 ① Clinical recovery: After 3 to 4 months of treatment, the main symptoms disappeared, and then the test indicators fully met the remission conditions. Continuous medication could maintain remission, and the test indicators were completely normal.

 ② Significant: The main symptoms improved within 3 to 4 months of treatment, and most of the comorbidities disappeared. The test indicators basically met the remission conditions, and the condition of continuous medication was stable.

 ③ Effective: The main symptoms and comorbidities have improved within 3 to 4 months of treatment, and some of the test indicators meet the remission conditions.

 ④ Ineffective: treatment for more than 6 months, although the main symptoms and comorbidities have improved and unstable, and occasionally treatment indicators.

 Mitigation conditions:

 ① Anti-nuclear standard NA) titer decreased significantly (<1: 40).

 ② ANA fluorescence pattern changed from peripheral type to homogeneous type or speckle type or disappeared.

 ③ ds-DNA antibody was negative to low titer (<20%).

 ④ Lupus cells are negative.

 ⑤ Complement C3 rose back to normal.

 (4) Observation indicators

① SLEDAI score, that is, the most representative 24 or more symptoms or manifestations of SLE activity are assigned to the corresponding scores; including: A: epilepsy, psychotic symptoms, organic brain syndrome, visual impairment, cerebral nerve damage, Headaches, cerebrovascular accidents, vasculitis manifestations, 8 points for each of the above; B: arthritis, myositis, cast urine, hematuria, proteinuria, pyuria, all 4 points above; C: rash, hair loss, mucosa Ulcers, pleurisy, pericarditis, hypocomplementemia, and anti-double-stranded DNA titers were all 2 points. The total score is the SLEDAI of the crying patient, ranging from 0 to 105 points. It is generally considered that the total score is <9 points for inactive periods,> 9 points, <20 points for active periods, and> ²⁰ points for significant active periods.

 ② Conventional and biochemical indicators

 Including 24h urine protein, Bun, Cr.

 ③ immune index serum

 Including ANA, DS-DNA, lgG, C3, ESR.

 ④ Observation indicators of adverse reactions

 RBC WBC platelets, AST, ALT.

7. Statistical processing The measurement data is tested and the counting data is X ² test. All statistics are applied. SPSS 10. 0 statistical software is used to complete.

 (B) Results

1. The clinical efficacy is shown in Table 3:

 Table 3 shows that the total treatment efficiency is 90%, and there is no significant difference compared with the control group, which indicates that the total glycosides of paeony paeony has a curative effect on SLE.

 1. See Table 4 for changes in disease activity before and after treatment.

 Changes in SLEDAI score before and after treatment

 Table 4 shows that the SLEMI score has improved significantly after treatment, and the three segments have very significant differences compared to before treatment (** p <0.01).

 3. The changes in ^ function before and after treatment are shown in Table 5:

Table 5 shows a significant improvement in renal function after treatment. 4. Table 6 shows the changes of immunological parameters before and after treatment.

 Table 6 ESR, ANA, Ds-DNA, IgG, C3 before and after treatment

 Table 6 shows that the serum erythrocyte sedimentation rate, ANA, IgG, and C3 of the patients before and after treatment were significantly improved compared with those before treatment. * P <0.05

 5. For adverse reaction observations, see Table 7:

 Table 7 shows that after 6 months of treatment, the patient did not appear liver damage, but the levels of AST and ALT were lower than before treatment, indicating that it has no toxic side effects on the liver, but also has a protective effect on the liver. In addition, Hb and WBC were not significantly lower than before treatment, and the number of platelets increased. * p <0. 05.

 6. Other adverse reactions: Some patients have diarrhea, which can be tolerated if mild.

 Third, the conclusion

According to pharmacological studies of total glucosides of paeony, total paeony can inhibit the proliferation of B cells and reduce the secretion of autoantibodies. And can reduce blood _{TNFo IL-2, 2, LTB} 4, and the level of oxygen radicals inflammatory mediators PGE inflammatory cytokines. These pharmacological effects allow the total glucosides of paeony to inhibit abnormally hyperhumoral immunity in SLE patients, reduce the attack of normal tissues by autoantibodies, and damage to the body by autoimmune inflammation.

 In this study, the total glucosides of paeony were used to treat SLE, and it was found that it can effectively control disease activity, reduce disease and immune globulin levels, and its efficacy is equivalent to glucocorticoids, but it can reduce the amount of hormones and reduce the occurrence of side effects of hormones. An effective way to treat systemic lupus erythematosus. BRIEF DESCRIPTION OF THE DRAWINGS

 Figure 1 shows the high-pressure liquid phase analysis of total glucosides of paeony.

FIG. 2 is a high-pressure liquid phase analysis spectrum when analyzing changes in cattle. FIG. 3 is a high pressure liquid phase analysis chart of total glucosides of paeony after further purification.

Among them, in Figure 1, the column: 0DS 4. 6 200mra, wavelength: UV- 260nm, mobile phase: CH ₃ 0H- H ₂ 0: 30-100 gradient, flow rate: lml / min; in Figure 2, mobile phase: 10 -40% (acetonitrile: 0.1% phosphoric acid water) (0-15min), 40% (acetonitrile: 0.1% phosphoric acid water) (15-40min), flow rate: lml / min, wavelength: 230 legs, Column: 0DS 4. 6 25 Oram (5u); In Figure 3, flow rate: 1. Oml / min, mobile phase: acetonitrile: phosphoric acid water (0.1%) = 17%-40% (20min) ~ 40% ( 25min)-17 (30min) ~ 17% (35min), color column: HiQs il C18 (4.6 x 150 x 150), detection wavelength: 230 ships, paeoniflorin retention time is 8.3 minutes. detailed description

 The present invention is further illustrated by the following examples, but is not limited thereto.

 Example 1

 Take the qualified white peony, prepare it according to the method described above, add an appropriate amount of 90% ethanol, heat to extract, and concentrate; the concentrated solution is extracted with a mixed solution of n-butanol and ethyl acetate, concentrated, dried, and pulverized, and passed through a 100-mesh sieve. Install No. 3 capsules to obtain the total glycoside capsule of Paeonia lactiflora.

Wu, female, 60 years old, retired civilian. Mainly due to "dry mouth and dry eyes with systemic polyarthralgia, recurrence with fever more than half a month", physical examination: bulbar conjunctiva and oral mucosa dry, multiple oral ulcers, right index finger metacarpophalangeal joint and right foot toe redness and pain, tenderness, floating Test (+). Blood routine showed: HB 8. 5g, white blood cells 6.7 * 10 ⁹ / L, platelets were normal, 'urine routine showed: protein ++, normal routine, ESR 10 ⁵ crypto / h, CRP 5.82, electrolyte, biochemical no abnormalities, an Ig, no abnormalities of complement, serum globulin, HLA-B27 (-), AKA (-), recessive RF (-), P- ANCA ( -), ACL- I g M (- ), APF, DNP, ENA, AHA, PCNA, ds wake, ANA (-), ECG is normal, no abnormalities on the chest radiograph were diagnosed in March 2002: 1. Sjogren's syndrome, 2. Osteoarthritis. Giving paeony total glycosides orally (3 times a day, 0.6 g each time, 6 months of treatment) and vitalin treatment, one month later, the symptoms of dry mouth and dry eyes improved, oral ulcers healed, and joint pain symptoms eased, Futalin was discontinued, and the total glucosides of paeonia lactiflora were maintained for six months. The condition was stable, and the tests were normal and cured.

 Example 2

Preparation of capsules is the same as in Example 1; Chen, female, 40 years old, Han, married, Beijing nationality, bank employee. The patient developed intermittent dry mouth and dry eyes 8 years ago ^ ¾. 7 months ago there was no cause of fever, Body temperature up to 39 ° C. No cold, chills, hot irregularities, dry eyes. When eating dry and hard food, you need to take water, hair loss, no photosensitivity, mouth ulcers, sore throat, dry cough, pain in both knees, left elbow, left wrist, and shoulder joints, non-walking, about half an hour in the morning. Examination: The whole body was dry and no rash or subcutaneous nodules were seen. Schober test (+). Laboratory tests: ANA (+), anti-SSA (+), anti-SSB (+) diagnosed as Sjogren's syndrome. Treat the white bitch with total bitter gum, 0.6 g / time, 3 times / day. After taking the medicine for 1 month, her temperature returned to normal and her joint pain eased. She continued treatment. At 4 months, the symptoms of dry mouth and dry eyes improved, and the ESR was 18 faces / h. The immunoglobulin decreased by 4%, and the clinical relief was achieved.

 Example 3

 The capsules were prepared as in Example 1; Yuan Π, female, 51 years old, Han nationality, married, Beijing nationality, worker. The patient had no obvious inducement for dry mouth 4 years ago, drinking more water, and the symptoms of dry mouth gradually worsened, no eye discomfort, 3 years ago, he began to feel itching and pain after sun exposure on both forearms, and most of them were scattered in bright red millet grains. No loss of appetite, no fever, no joint swelling and pain, no diagnosis and treatment. 1 year ago, he had faint pain in the right liver area, nausea, and no vomiting. On examination, the oral mucosa was dry and the liver area was lightly buckled. ALT 434 U / L, AST 440 U / L, TBIL 33. 8 umol / L, DBIL 16. 7 umol / L, ALP 197 U / L, GGT 182 U / L. Hepatitis B, C, D, D, and E markers were negative, ESR was accelerated, IgM was increased, and liver protection therapy was relieved. Diagnosis: 1 Sjogren's syndrome, 2. Immune liver damage. Treated with peony total glycoside capsules, 0.6 g / time, 3 times / day. After taking the medicine for 3 months, the pain in the liver area disappeared and the liver function returned to normal. Continue treatment, dry mouth and dry eye symptoms improved after 6 months, immunoglobulin decreased to normal, clinical relief.

 Example 4

 The capsules were prepared as in Example 1; Jia, female, 47 years old, Han, married, teacher, Hebei nationality. Patients had no incentive for more than 10 years to show that their hands turned white and purple after encountering cold water. 9 years ago, they had conscious dry eyes and dry mouth. They became worse 6 years ago, and they need to drink water when eating dry food. After treatment with Chinese medicine for 1 year, it improved. Since then, the patient still has the above symptoms, which is lighter than before, without parotid enlargement, but the dental caries has increased in recent years. On examination, the mucosa of the cavity was dry, there were more dental caries, no oral ulcers, Raynaud's phenomenon in both hands, Schober test (+). Laboratory tests: Anti-SSA (+) and anti-SSB (+) were diagnosed as Sjogren's syndrome. Treated with peony total glycosides capsules, 0.6 g / time, 3 times / day. After 6 months of taking the medicine, the symptoms of dry mouth and dry eyes improved, and the clinical relief was achieved.

 Example 5

The preparation of total glucosides of Paeonia lactiflora is the same as in Example 1; Wu, female, 73 years old. Oral mucosal ulcers started in May 1990, with recurrent episodes, followed by sore throat, hoarseness, sputum and sometimes bloodshot, with redness in both eyes, He had been seen in a hospital and was diagnosed as "membranous pharyngitis", "ulcerative moss osteomyelitis", "stomatitis", "oral ulcer", etc. He had been treated with various antibiotics and vitamins. Obvious effect,

Ulcers appeared in the limbs at the beginning of 1993. Six months later, the upper abdomen was uncomfortable with ascites, edema in both lower limbs, and external ulcers. Behcet's disease was diagnosed in June 1996, and the total glycosides of paeonia lactiflora were given 0.6 g / time. Three times, the ulcers healed after 2 months, and the symptoms disappeared. The total glucosides of paeony were taken alone for maintenance treatment, and there was no recurrence during one year's follow-up. '

 Example 6

 Preparation of capsules is the same as in Example 1; Li, female, 37 years old. Oral ulcers started 10 years ago with recurrent episodes of redness in both eyes. 6 months ago, the above symptoms recurred and external ulcers appeared. Behcet's disease was diagnosed. Paeonia lactiflora glycosides were administered 0.6 / times, 3 times a day. After 2 months, the ulcers healed and the eye symptoms disappeared. Take alone Paeonia lactiflora and paeoniflorin were maintained for treatment, and there was no recurrence during a follow-up of one year.

 Example 7

Preparation of capsules is the same as in Example 1; Sun, male, 46 years old, cadre. Multiple oral ulcers and joint pains occurred half a year ago, including swelling and pain in the hands, the interphalangeal joints of both feet, and the wrists. Examination revealed multiple oral ulcers, three proximal interphalangeal joints, right, second, third, and fifth proximal interphalangeal joints with swollen swelling and tenderness, tenderness and swelling on the left knee joint, and floater test (-). Sternoclavicular and mandibular joint tenderness. Check ESR 60mm / h, CRP 5. 57mg / dl ₀ diagnosed as Behcet's disease. Give Paeonia lactiflora total glycosides 0.6, 3 times a day. After 1 month, the patient's oral ulcers healed. The patient's condition is now better, and the pain in each joint is reduced than before. ESR 25 / h, CRP 3. 12mg / dl Remission.

 Example 8

 The capsules were prepared in the same manner as in Example 1; patient Pang, female, 21 years old, unmarried, Han nationality, Beijing nationality, student. One and a half years had multiple oral ulcers, iridocyclitis, and intermittent low fever, pain in joints such as knees and ankles, no obvious swelling, and no vulvar ulcers. ANA 1: 320 negative, dsDNA negative, anti-histone antibody negative, HLA-B27 negative, X is normal. Behcet's disease was diagnosed, and the total glucosides of paeony were taken 0.6 / times, 3 times a day. After 4 months, the patient's oral ulcers healed and the iris ciliary body inflammation was cured. The total glucosides of paeony were taken alone for maintenance treatment and followed up for one year. No recurrence.

 Example 9

Preparation of capsules is the same as in Example 1; Lee, female, 62 years old. Mainly due to "dry mouth and dry eyes with polyarthritis of the whole body for more than 6 years, with breathing effort for 1 year", physical examination: dry bulbar conjunctiva and oral mucosa, more Mouth ulcers, swelling and pain in the metacarpophalangeal joints of the right index finger and right toe, tenderness, and floater test (+). Blood routine showed: HB 8. 5g, white blood cells 6, ⁷ * 10 ⁹ / L, normal platelets, normal urine and stool, ESR 105 crypto / h, CRP 5.82, no abnormalities in electrolytes, biochemistry, Ig, complement Abnormal, elevated serum globulin, negative autoantibodies, normal ECG, chest radiograph showing double lung cord-like high-density shadow, lung function showed TLC 3. 2L, FVC 2.1 1L, DLCO 14ml / min. MmHg in 2002 The diagnosis in March was: 1. Sjogren's syndrome secondary to pulmonary interstitial fibrosis. She was given orally (3 times a day, 0.6g each time, 6 months of treatment) and Futalin. After one month, her mouth and dry eyes were cured, heralgia and arthralgia were healed. Remission, withholding of Voltarin, Paeonia lactiflora peptone maintenance treatment. Dyspnea improved after two months. Six months later, the lung and lung function showed TLC 3. 8L, FVC 2. 7L, DLC0 25ml / min. MmHg, the condition was stable, all tests were normal, and healed.

 Example 10

Preparation of capsules is the same as in Example 1; Wu, female, 70 years old, retired civilian. Fifteen years ago, he had dry mouth and eyes and polyarthritis all over his body. Diagnosis of Sjogren's syndrome, rheumatoid arthritis. Taking methotrexate and anti-inflammatory drugs and other treatments relieved joint swelling and pain, and improved symptoms of dry mouth and eyes. After that, there were still recurrent attacks. In the past year, he has had difficulty breathing and his symptoms of dry mouth and eyes have worsened. Physical examination: Dry mouth and eye mucous membranes, clear lungs and clear breathing, no pleural friction sounds and wet and dry rales. Right index finger metacarpophalangeal joint and right foot forefinger redness, swelling, pain, tenderness, floating palate test (+). Laboratory tests: Blood routine shows: HB 8. 5g, white blood cells 6.7 * 10 ⁹ / L, normal platelets, urine routine shows: protein ++, normal routine, ESR 105 bands / h, CRP 5.82, electrolyte, biochemical No abnormalities were seen, Ig, complements were normal, serum globulin was elevated, HLA-B27 (-), AKA (-), recessive RF (-), P-ANCA (-), ACL-IgM (-) , APF, DNP, ENA, AHA, PCNA, dsDNA, ANA (-), ECG was normal, chest radiograph showed high-density shadows of both lungs, and lung function showed decreased compliance. The diagnosis was: 1. Sjogren's syndrome and interstitial fibrosis, 2. Rheumatoid arthritis. The total glucosides of paeonia lactiflora were orally administered (3 times a day, 0.6 g each time) and other drugs such as butalin.

 Joint swelling and pain were relieved after 3 months. After taking the total glucosides of paeonia lactiflora, the lung function TLC, FVC, DLC0 and other indicators improved after 6 months. The condition improved, followed by medication.

 Example 11

Preparation of capsules is the same as in Example 1; Jia, female, 52 years old. Dry mouth and dry eyes with systemic polyarticular pain for more than 7 years, with breathing effort for 1 and a half years. Examination: dry bulbar conjunctiva and oral mucosa, multiple oral ulcerations, multiple dental caries. Swelling and tenderness of multiple metacarpophalangeal joints, tenderness (+), swelling of the knee joint, and floater test (+). ESR 95mm / h, CRP6.2, serum globulin increased, all autoantibodies were negative, ECG was normal, chest radiograph showed double-stranded high-density shadow, lung function showed TLC 3. OL, FVC 2. 2 L, DLCO llml / min. mraHg _{0 is} diagnosed as: 1. Sjogren's syndrome secondary to pulmonary interstitial fibrosis. Oral administration of total glucosides of Paeonia lactiflora (3 times a day, 0.6 g each time, 6 months of treatment) and Futalin treatment. After 3 months, the symptoms of dry mouth and mugengan improved, oral ulcers healed, and joint pain symptoms Remission, withholding of Voltarin, paeonia glycosides and capsules maintenance treatment.

Breathing improved after 6 months. Re-examination of lung function showed TLC 3. 9L, FVC 2. 9 L, DLC0 27ml / min in. MmHg, and the disease was better.

 Example 12

 The capsules were prepared as in Example 1; Guan, female, 61 years old, Han, married, Beijing nationality, worker. The patient developed dry mouth 7 years ago, drinking more water, and the symptoms of dry mouth gradually worsened, without eye discomfort. He began to have trouble breathing 1 year ago, no fever, no joint swelling and pain, and no parotid enlargement. many. On examination, the oral mucosa was dry, there were more caries, no oral ulcers, Raynaud's phenomenon in both hands, and Schober test (+). Assays: anti-SSA (+), anti-SSB (+). The chest radiograph showed ^^ cord-like high-density shadows. Pulmonary function showed reduced vital capacity and decreased lung compliance. Diagnosis of Sjogren's syndrome and pulmonary interstitial fibrosis. Treated with peony total glycoside capsules, 0.6 g / time, 3 times / day. After 6 months of taking the medicine, the symptoms of dry mouth and dry eyes improved, and the lung function returned to normal after review, and the clinical relief was achieved.

 Example 13

 The capsules were prepared in the same manner as in Example 1; Yang, female, 30 years old, first diagnosed in October 2001. Complaint: Pain in the whole body for more than 5 years, aggravated for 10 days, neck, lumbosacral, joint muscle pain in the extremities, soreness or soreness, with anxiety, dreaming, mental fatigue, fatigue, weakness, pain related to emotional changes, The steroidal anti-inflammatory drugs Fenbide and Vitalin did not improve. Examination of the joints of the extremities without swelling, suboccipital muscle, upper edge of trapezius, upper part of sacral gland, upper medial arm, humerus distal upper ankle, upper gluteal quadrant, posterior trochanter, internal knee tenderness The blood routine, AS0, RF, and ANA were normal, and the total glucosides of Paeonia lactiflora were given 600 mg 3 times a day. After four weeks, the pain was relieved, and anxiety, dysfunction, and fatigue were improved. There was no recurrence after 6 months of follow-up.

 Example 14

Preparation of capsules is the same as in Example 1; Liu, female, 46 years old, farmer. He suffered from soreness, discomfort, anxiety, dreaming, mental fatigue, fatigue for 1 year, and no fever rash. Examination: no redness and swelling in the joints of the limbs', the upper edge of the trapezius muscle, the start of the superior ganglia muscle, the upper medial side of the arm diaphragm, the upper outer side of the humerus ^ ¾ the upper buttock quadrant, The tenderness of the thumb behind the great trochanter, ESR 31mm / h, CRP 2. 43, blood routine, AKA, APF, AS0, RF, ANA were normal. Diagnosis of fibromyalgia syndrome. Give Paeonia lactiflora capsules 600 mg three times a day. After 2 months, the pain was relieved and fatigue was improved. There was no recurrence after 6 months of follow-up.

 Example 15

 Preparation of capsules is the same as in Example 1; Zhao, female, 34 years old. Whole body pain was worsened for more than 3 years. Neck, lumbosacral, limb muscle pain, soreness or soreness, accompanied by fatigue and weakness. Pain was related to emotional changes. It has not been improved with Fenbide and indomethacin treatment. Examination of the joints of the extremities showed no redness and swelling, suboccipital muscles, start of the superior ganglia, upper medial arm brachii muscles, distal humerus outer and upper ankle, upper gluteal quadrant, thumb tenderness, blood routine, AS0, RF, ANA were normal. Diagnosis of fibromyalgia syndrome. Give Paeonia lactiflora capsules 600 mg three times a day. After 1 month, the pain was relieved and fatigue was improved. The above symptoms resolved completely after 3 months, and there was no recurrence after 6 months of follow-up.

 Example 16

 Preparation of capsules is the same as in Example 1; Xie, female, 38 years old, unemployed. The main cause was "repeated systemic pain for 3 years, recurrence and exacerbation for 2 weeks". He came to the clinic in March 2002. Physical Examination: Swelling and tenderness of joints throughout the body, tenderness in the lower neck, trapezius, humerus, palate, hips, trochanter, and knees. No erythema, oral ulcers. There were no abnormalities in ESR, CRP, IgG, IgA, and complement, and no abnormalities in muscle enzymes and liver function. AKA (-), HLA-DR4 (-), RF (-), recessive RF (-), P-ANCA (- ), ACL-IgM (-), APF, ID, ENA, AHA, PCNA, dsDNA, and ANA were all negative. Fibromyalgia syndrome was diagnosed. Paeonia lactiflorin capsules were given 3 times a day, 600 mg each time, and pain was relieved after 6 weeks. Continue to take the medicine without any recurrence for 6 months.

 Example 17

Preparation of capsules is the same as in Example 1; patient Zhang, male, 20 years old, student. Two years ago, there was stiffness in the lumbar bone, 22 pairs of hip pain, and progressive worsening. When admitted to the hospital, squatting and bending was restricted. Morning stiffness> 30ηύη, night pain worsened. Turn over and get out of bed, it is difficult to squat to urinate, and occasionally low pad. Examination of the waist straight: Schober test (+), bilateral sagittal joint tenderness, "4" test (+), left hip flexion is limited in flexion, sacroiliac X-ray shows bundled damage, Erythrocyte sedimentation 43mm / n, rheumatoid factor (-), admission diagnosis of ankylosing spondylitis, paeoniflorin total glycosides capsules 0.6g / times, 3 times a day, orally, plus futalin, 4 weeks after treatment, Pain in the lumbosacral region of the patient was significantly relieved, nonsteroidal anti-inflammatory drugs were discontinued, and the total glucosides of paeony were continuously taken. On the 8th week, walking and gait returned to normal. ESR drops to Normal 10mm / h, squatting and bending were basically normal. At the 12th week of treatment, X-ray of the joints showed no active lesions and no adverse reactions during the treatment.

 Example 18

 Preparation of capsules is the same as in Example 1; Yao, male, 15 years old, student. He was admitted to the hospital in April 2002 mainly because of "fever, more than one week of swelling and pain." Physical examinations: Tenderness in the palate, swelling in the left elbow, tenderness, swelling in the left ankle, swelling, tenderness in the right knee, and floating palate test (+). ESR 92 band / h, CRP 7. 90, IgG increased, globulin increased, HLA- B27 (+). Shuangyao joint arthroplasty showed approximately normal, CT results showed changes in sacroiliitis, and the diagnosis was: serum-negative spinal arthritis, Rett syndrome. She was treated with 600 mg of total glucosides of paeony (unit t. I. D.) And treated with vitaline. After 3 months of treatment, the joint pain was relieved, and the ESR and CRP were reviewed. The condition improved.

 Example 19

 Preparation of capsules is the same as in Example 1; Wang, male, 19 years old, Han, unmarried, Beijing nationality, student. The patient was induced by lumbosacral pain 1 year ago, apparent at night, pain in both wrists, ankles, and knees 6 months ago, without obvious swelling and restricted movement, with mild fever, body temperature of 38 ° C, physical examination : The lumbosacral tenderness is obvious, the lumbar pushing activity is acceptable, and the "4" test is positive. Assay: ESR 85 / h, CRP6. 90, IgG increase, increase protein, HLA-B27 (+), ANA (-), anti-RNP antibody (-), anti-Sm antibody (-). The double sacroiliac joint radiograph showed bilateral arthritis changes in the skeletal scale and was diagnosed as ankylosing spondylitis. She was treated with 600mg of total glucosides of paeonia lactiflora, t.i.d., and vitalin after 5 months of joint pain relief. The ESR and CRP were re-examined. Shuangtuoteng joint film showed that sacroiliac arthritis was alleviated, and her condition improved. She continued to take medication.

 Example 20

Preparation of capsules is the same as in Example 1; Wu, female, 21 years old, Han, unmarried, student. The patient had no inducements for facial reddish-red erythema, pain in both knee joints and individual finger joints before 9 and a half years ago. He was examined for blood: PLT 35,000 / L, urinary protein (++++), and diagnosed as "systemic lupus erythematosus." ,,, Prednisone 60mg QD and cyclophosphamide static point treatment, urine protein turned negative, symptoms subsided. 1 year ago, the above symptoms relapsed after steroid hormone medicine was stopped for half a year, urine protein (++++), and Symptoms such as alopecia and oral ulcers appeared. She was treated with tripterygium glycosides and her menopause was not relieved. She was treated with prednisone 60 mg QD and cyclophosphamide, and then reduced to prednisone 20 mg once every other day. However, urine protein (++) was given to Paeonia lactiflora capsules, 0.6 g / time, 3 times / day. After 6 months of continuous taking, urine protein turned negative, erythema and joint pain symptoms disappeared, and complement increased. Clinical remission. Example 21

 Preparation of capsules is the same as in Example 1; Sun, female, 50 years old, Han, married, cadre. One year ago, there was no obvious cause of pain in both ankles, no swelling, red rash on the whole body after light exposure, fatigue, general pain, and low fever. Symptoms worsened in the afternoon. Physical examination: Diffuse swelling of the soft tissue of the silent hand and wrist joint with tenderness, no joint deformities, tenderness of the knee, no swelling. Auxiliary tests: rheumatoid factor positive, antinuclear antibody positive, anti-double-strand DNA positive. Diagnosis of systemic lupus erythematosus. I took the total glucosides of paeonia lactiflora, capsules, 0.6 g / time, 3 times / day. After taking it for 3 consecutive months, the low fever disappeared, and the joint pain disappeared. After 6 months, the anti-double-stranded DNA turned negative, and there was no recurrence of joint pain, and the clinical relief was achieved.

 Example 11

 Preparation of capsules is the same as in Example 1; Hou, male, 16 years old, student. Patient 10 months ago after sun exposure? On the other eyelid, bilateral crotch, and nasal bridge there were flaky erythema, and the patient was consciously weak, without any symptoms such as fever and joint pain. Later, facial erythema appeared repeatedly, the symptoms were basically the same as before, and red papules on the fingertips of both hands appeared, with mild tenderness. Fever occurred 4 months ago, up to 39.6 ° C, accompanied by redness and swelling around the left ear, fatigue after severe exercise, swelling of the lymph nodes in the neck, and muscle aches throughout the body, accompanied by low fever of about 37.5 ° C, followed by Swelling of the right parotid gland. Physical examination: bilateral submandibular, anterior neck, axillary, and groin can reach several superficial lymph nodes the size of soybean, with mild tenderness. A small amount of purulent discharge was seen in the bilateral parotid duct openings. ESR85 leg / h, ANA (+) 1: 640s RF283U / L anti-ulRNP antibody (+) anti-Sm antibody (+), diagnosed as systemic lupus erythematosus. She was treated with total glucosides of paeony, 0.6 g / time, 3 times / day, and after taking the medicine for more than 20 days, the right parotid gland swelling and body temperature decreased. After 2 months, the erythema on the back disappeared, ESR16mm / h, clinical remission.

 Example 23

The capsules were prepared in the same manner as in Example 1; Meng, female, 49 years old, Han, unmarried. The patient had no cause for swelling, pain, morning stiffness, low fever, and facial rash before 5 months. The patient's joint pain was migratory, and the joints of the fingers, wrists, elbows, shoulders, ankles, and knees were affected. Except for the joints of the hands, the rest of the joints were not significantly red and swollen and had limited movement. The interphalangeal joints and wrist joints Swelling is obvious, morning stiffness is greater than 1 hour. With mild fever, body temperature was 38 ° C. The facial rash was dark red, not higher than the skin surface, no dandruff on the surface, and dermatitis did not worsen after sun exposure. Blood test routine: WBC 3500 / mm ³ , GR 47%, LY 46 ° / o, Hb 109g / L, PLT 118 * 109 / L, ANA (+), DNA-Farr29. 0%, DNA-IF (+) , Anti-RNP antibody (-), anti-Sm antibody (-), diagnosed as systemic lupus erythematosus. Treatment of total glucosides of paeony, 0.6 g / After three or three times a day, the joint pain was significantly relieved, morning stiffness was reduced, swelling and pain in the proximal knuckles of both hands were reduced, and the fever and rash subsided. The treatment continued for 5 months without recurrence of symptoms and clinical relief.

 Example 24

The main steps of preparing the paeony glucoside tablets are the same as those in Example 1, and the paeony glycoside powder is sieved through a 100-mesh sieve, an appropriate amount of auxiliary materials is added to form granules, and then pressed into tablets, and then can be made. Wu, female, 60 years old, retired civilian. Mainly due to "dry mouth and dry eyes with systemic polyarthralgia, recurrence with fever for more than half a month", each examination: bulbar conjunctiva and oral mucosa dry, multiple oral ulcers, right index finger metacarpophalangeal foot food address swelling and pain, tenderness, floating ， ¾¾ 佥(+). Blood routine shows: HB 8. 5g, white blood cells 6.7 * 10 ⁹ / L, blood is small ^ L often, urine routine shows: protein ++, then often, ESR 105mm / h, CRP 5.82, electrolytes, biochemical See abnormalities, Ig, no abnormalities, elevated serum globulin, HLA-B27 (-), AKA (-), recessive RF (-), P-ANCA (-), ACL-IgM (-), APF, DNP, ENA, AHA, PCNA, dsDNA, ANA (-), ECG were normal, and no abnormalities were found on the chest radiograph. They were diagnosed in March 2002 as: 1. Sjogren's syndrome; 2. Osteoarthritis. Oral administration of total glucosides of paeony (3 times a day, 0.6g each time, 6 months of treatment) and Futalin treatment, one month later, symptoms of dry mouth and dry eyes improved, oral ulcers healed, arthralgia symptoms », discontinued Futalin and total glucosides of paeony were maintained for six months. The condition was stable, and the tests were normal and cured.

 Example 25

 Preparation of capsules is the same as in Example 1; Zhang, male, 56 years old, worker. He suffered from hepatitis B 5 years ago, and his transaminase decreased after taking Chinese medicine. His symptoms and signs were reduced. After repeated relapses due to fatigue, the symptoms persisted. In the past six months, anorexia and jaundice have appeared. Transaminases have been checked more than normal several times. B-ultrasound showed hepatic lobular hyperplasia, showing the early manifestations of liver cirrhosis. Laboratory tests: ALT634U / ml, AST576U / ml, TB233 | omol / ml, A35g / L, G34g / L, HA233 g / ml, LN143 g / ml, PCIII145 g / ml, diagnosed as chronic persistent hepatitis with liver fibrosis . Oral administration of total glucosides of Paeonia lactiflora (3 times a day, 0.6 g each time), and general liver-protective treatments such as maggot aspartate and Gan Taile. After 6 months, the symptoms of appetite and jaundice improved. Review ALT234U / ml, AST201U / ml, TB89μπο1 / πι1, A42g / L, G31g / L, HA119 g / ml, LN89 g / ml, PCin i02 g / ml, liver function And liver fibrosis indicators improved. Clinical relief, follow-up medication follow-up.

 Example 26

Preparation of capsules is the same as in Example 1; Wang, male, 38 years old, company employee. He suffered from hepatitis B 3 years ago, and his symptoms improved after treatment. However, liver function tests were abnormal several times and no systemic treatment was performed. Nearly 9 Over the past month, the symptoms of anorexia and jaundice have recurred, and hepatic pain has appeared. A B-ultrasound showed hepatic lobular hyperplasia, which was an early manifestation of cirrhosis. Chemical risk inspection: ALT534U / ml, AST511U / ml, TB202 ^ ol / ml, A32g / L, G38g / L, HA245 g / ml, LN122 g / ml, PCIII137 g / ml, diagnosed as chronic persistent hepatitis with liver fiber Into. Oral administration of total glucosides of paeonia lactiflora (3 times a day, 0.6g each time), and general liver-protecting treatments such as aspartate magnesium asparagus, Gan Taile and so on. 6 month appetite, jaundice and liver pain symptoms improved, review ALT184U / ml, AST191U / ml, TB67 ^ ol / ml, A39g / L, G32g / L, HA8 g / ml, LN76 g / ml, PCIII99 g / ml, liver function and liver fibrosis index improved. Clinical relief, follow-up medication follow-up.

 Example 27

 Preparation of capsules is the same as in Example 1; Song, female, 34, accountant. Intermittent fever, multi-joint pain, and semi-red rash pointer occurred 6 years ago. At that time, white blood cells were detected, ANA (+) was detected in hemoglobin, SLE was diagnosed, and the prednisone 30 mg (unit qd) was given. The condition improved after treatment. .Reduced to 5mg q. D. Half a year ago, he developed worsening fatigue, weight gain, eye puffiness, hoarseness, and lethargy. Test ANA 1:80. m- MA (+), blood routine WBC3.7THSD / CU HGB9.5 GRAMS / DL ESR76 hidden / h, IgA9.76g / L, IgG20g / L, T3 <33Ug / dl, T4 <2Ug / dl, TSH> 324U / ml, FT3, FT4 were all less than 2Pmol / L. B-ultrasound right lobe hemangiomas were diagnosed as dry eye by Mugen, and there were no abnormalities in electrocardiogram and chest radiograph. Examination: T: 36.6 ° C, BP95 / 65mmHg, P64 times / min, hoarseness, swollen face, and pale conjunctival negative. Combined with his history of functional uterine bleeding, diagnosis: systemic lupus erythematosus, hypothyroidism, functional uterine bleeding, dry eye M positive, oral administration of total glucosides of paeony 600 mg / time, three times a day, excellent Melody 50Vgq.d and Lixuesheng, Inosine, Funad, and Syndari will be treated symptomatically. Fever ceased after one month, joint pain was relieved, rash subsided. After 6 months of treatment, the condition was stable and completely relieved.

Claims

Rights request

1. Application of total glucosides of paeony in the preparation of medicines for treating or preventing primary Sjogren's syndrome.

 2. Application of total glucosides of paeony in the preparation of medicines for treating or preventing Behcet's disease.

 3. Application of total glucosides of paeony in the preparation of medicines for treating or preventing pulmonary interstitial fibrosis disease.

 4. Application of total glucosides of paeony in preparing medicine for treating or preventing fibromyalgia syndrome.

 5. Application of total glucosides of paeony in the preparation of medicines for treating or preventing ankylosing spondylitis.

 6. Application of total glucosides of paeony in the preparation of medicines for treating or preventing liver fibrosis diseases.

 7. Application of total glucosides of paeony in the preparation of medicine for treating or preventing systemic lupus erythematosus disease.

8. The use according to claim 1, 2, 3, 4, 5, 6, or 7, characterized in that an effective amount of paeoniflorin, peony lactone, hydroxypaeoniflorin, and benzoyl paeoniflorin is used in specific applications. The pharmaceutical composition is composed of the components composed of other ingredients and a pharmaceutically acceptable carrier.

 9. The application according to claim 8, characterized in that the composition composed of the components and the pharmaceutically acceptable carrier is a pharmaceutical composition, and the pharmaceutically acceptable carrier refers to any standard pharmaceutically acceptable carrier.

 10. The application according to claim 8, characterized in that it can include additives for tablets, granules, capsules and the like; it can also include fragrance and color additives or other ingredients, and the composition containing the carrier can be Convenient method formulations are known.