Traditional Chinese medicine compound for treating chronic kidney diseases

Abstract

The invention relates to the technical field of traditional Chinese medicine, and discloses a traditional Chinese medicine compound for treating chronic kidney disease, the traditional Chinese medicine compound is composed of 20-40 parts of raw rhubarb, 30-60 parts of calcined oyster, 20-40 parts of red sage root, 20-40 parts of dandelion, 15-30 parts of Chinese starjasmine stem, and 15-30 parts of serissa serissoide, the calcined oyster is prepared by calcining oyster shell and crushing the calcined oyster shell into 100-200 mesh fine powder, and the medicine is administered through rectal perfusion. The traditional Chinese medicine composition is taken twice a day, is reserved for 30-60 minutes each time, and can reduce serum creatinine and urea nitrogen levels, improve the glomerular filtration rate and protect the renal function. The raw rhubarb, the calcined oyster shell, the red sage root, the dandelion, the Chinese starjasmine stem and the serissa serissoide are scientifically matched to achieve a synergistic effect. The raw rhubarb has the effects of relaxing bowels and discharging turbidity, the calcined oyster adsorbs toxin, the salvia miltiorrhiza has the effects of promoting blood circulation and removing blood stasis, the dandelion has the effects of clearing away heat and toxic materials, the Chinese starjasmine stem has the effects of dispelling wind and dredging collaterals, and the serissa serissoide has the effects of promoting diuresis and descending turbidity, so that a multi-target treatment system of activating blood, detoxifying, discharging

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and specifically relates to a traditional Chinese medicine compound for treating chronic kidney disease. Background Art

[0002] Chronic kidney disease is a global public health problem. As the disease progresses, toxins accumulate in the patient's body. Traditional treatment methods such as hemodialysis are expensive and have complications. As a treatment method with Chinese medicine characteristics, traditional Chinese medicine enema therapy is vividly called "intestinal dialysis", which provides a new way for the treatment of chronic kidney disease. Based on traditional Chinese medicine theory, this therapy utilizes the absorption function of the colonic mucosa and the excretory function of the intestine. By perfusing traditional Chinese medicine liquid into the colon, the drug directly contacts the colonic mucosa, thereby playing the role of removing toxins from the body.

[0003] However, there are many problems with the traditional Chinese medicine enema prescriptions currently used in clinical practice, such as a single prescription and limited curative effect. The drug compositions of many enema prescriptions are relatively simple, often only focusing on one aspect of the effect, lacking comprehensive conditioning and synergistic effect. Due to the complex pathogenesis of chronic kidney disease, involving dysfunction of multiple systems and organs, it is difficult for a single-prescription enema prescription to comprehensively treat the patient's condition, thus limiting the exertion of its curative effect. Summary of the Invention

[0004] In view of the deficiencies of the prior art, the present invention provides a traditional Chinese medicine compound for treating chronic kidney disease, which solves the problems that the drug compositions of many enema prescriptions are relatively simple, often only focusing on one aspect of the effect, lacking comprehensive conditioning and synergistic effect.

[0005] To achieve the above objectives, the present invention is realized through the following technical solutions:

[0006] A traditional Chinese medicine compound for treating chronic kidney disease is composed of the following raw materials in parts by weight: 20 - 40 parts of Rheum officinale, 30 - 60 parts of Concha Ostreae, 20 - 40 parts of Salvia miltiorrhiza, 20 - 40 parts of Taraxacum mongolicum, 15 - 30 parts of Trachelospermum jasminoides, and 15 - 30 parts of Serissa japonica.

[0007] Preferably, it is composed of the following raw materials in parts by weight: 30 parts of Rheum officinale, 60 parts of Concha Ostreae, 30 parts of Salvia miltiorrhiza, 30 parts of Taraxacum mongolicum, 20 parts of Trachelospermum jasminoides, and 20 parts of Serissa japonica.

[0008] Preferably, the Concha Ostreae is the oyster shell calcined and pulverized into fine powder of 100 - 200 mesh.

[0009] Preferably, a preparation method of a traditional Chinese medicine compound enema for treating chronic kidney disease is used for the traditional Chinese medicine compound enema for treating chronic kidney disease, and the method includes the following steps:

[0010] S1. Decoct raw rhubarb, salvia miltiorrhiza, dandelion, trachelospermum jasminoides, and serissa japonica twice with water. For the first time, add 8 times the amount of water, bring to a boil, and then keep it simmering gently for 1 hour. For the second time, add 6 times the amount of water, bring to a boil, and then keep it simmering gently for 45 minutes. Combine the decoctions.

[0011] S2. Add the fine powder of calcined oyster to the above-mentioned decoction and stir evenly.

[0012] S3. Concentrate to obtain a medicinal liquid containing 1 - 2 grams of crude drug per milliliter, filter, sterilize, and package to obtain the product.

[0013] Preferably, in S3, it is concentrated to obtain a medicinal liquid containing 1.5 grams of crude drug per milliliter.

[0014] Preferably, the application of a traditional Chinese medicine compound enema in the treatment of chronic kidney disease drugs is for the above-mentioned traditional Chinese medicine compound enema for treating chronic kidney disease, and the chronic kidney disease is stage 3 - 4 chronic kidney disease, especially those with the syndrome type of damp-heat stasis obstruction.

[0015] Preferably, the drug is administered by rectal perfusion, 1 - 2 times a day, and each time it is retained for 30 - 60 minutes. The drug is absorbed through the rectal mucosa, avoiding the first-pass effect of the liver and improving the bioavailability.

[0016] Preferably, the drug can reduce the levels of serum creatinine and urea nitrogen, improve the glomerular filtration rate, and protect renal function.

[0017] Preferably, the drug can reduce the levels of inflammatory factors IL-1β and TNF-α and alleviate renal interstitial fibrosis.

[0018] Preferably, the clinical advantages of the drug include that compared with oral preparations, rectal administration can reduce the irritation to the gastrointestinal tract; compared with hemodialysis, it has the characteristics of simple operation, low cost, and high patient compliance; long-term use can delay the progression of chronic kidney disease and reduce the risk of end-stage renal disease.

[0019] The present invention provides a traditional Chinese medicine compound for treating chronic kidney disease, with the following beneficial effects:

[0020] 1. The present invention scientifically combines raw rhubarb, calcined oyster, salvia miltiorrhiza, dandelion, trachelospermum jasminoides, and serissa japonica to play a synergistic role. Raw rhubarb purges the bowels and discharges turbidity, calcined oyster adsorbs toxins, salvia miltiorrhiza promotes blood circulation and removes blood stasis, dandelion clears heat and detoxifies, trachelospermum jasminoides dispels wind and dredges collaterals, and serissa japonica promotes diuresis and reduces turbidity, forming a multi-target treatment system of "promoting blood circulation - detoxifying - discharging turbidity - adsorbing".

[0021] 2. The present invention adopts the method of directly adding fine powder of calcined oyster into the decoction liquid, which not only retains the adsorption effect of oyster, and thus can more effectively adsorb some impurities, harmful substances and components that may affect the efficacy of the medicine, thereby playing a role in purifying the decoction liquid and enhancing the overall efficacy, but also avoids the loss of active ingredients caused by traditional decoction, and further can ensure that the medicinal value of calcined oyster is maximally exerted, providing patients with higher-quality and more effective therapeutic drugs.

[0022] 3. By optimizing the concentration and retention time of the enema, the present invention ensures that the drug fully contacts the colonic mucosa, improves the bioavailability, and thus can effectively improve the bioavailability of the drug, enhance the therapeutic effect, and bring better therapeutic experience and hope for recovery to patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is a flow chart of a preparation method of a traditional Chinese medicine compound enema for treating chronic kidney disease according to the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0024] Next, the technical solutions of the present invention will be clearly and completely described in conjunction with the drawings of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts belong to the scope of protection of the present invention.

[0025] Example 1

[0026] 1. Analysis of the dosage ratio of raw materials

[0027] (1) Rheum officinale (30 parts):

[0028] Dose-effect relationship: Verified by orthogonal experiments, it can be seen from the 30-part dose that:

[0029] · Serum creatinine (Scr) is reduced by 23 - 28% (only 15 - 18% is reduced by 25 parts, and although 30% is reduced by 35 parts, the diarrhea rate reaches 20%)

[0030] · The best purgative effect (Bristol stool classification is maintained at type 4 - 5)

[0031] Compatibility characteristics: When the ratio with calcined oyster is 6:1, it can not only play the role of removing turbidity, but also be adsorbed by oyster to reduce intestinal irritation.

[0032] (2) Calcined oyster (60 parts):

[0033] Verification of adsorption performance:

[0034] Dosage (parts) Urea nitrogen adsorption rate Heavy metal adsorption rate 40 52％ 68％ 60 78％ 85％ 80 79％ 86％

[0035] 60 portions were selected because of the best marginal benefit (the highest adsorption rate / cost ratio).

[0036] (3) Salvia miltiorrhiza (30 portions) - Taraxacum mongolicum (30 portions):

[0037] Synergistic anti - inflammation: TNF - α inhibition rate = 0.82×Salvia miltiorrhiza dose + 0.76×Taraxacum mongolicum dose - 0.15×(interaction term)

[0038] Among them, when the ratio is 30:30, the inhibition rate reaches 64.2% (58.7% for 40:20 and 61.3% for 20:40).

[0039] (4) Trachelospermum jasminoides (20 portions) - Serissa japonica (20 portions):

[0040] Optimization of dampness - eliminating and collaterals - dredging:

[0041] ·When the amount is 25 portions, the risk of electrolyte disorder increases (the probability of serum potassium < 3.5 mmol / L rises to 18%).

[0042] Example 2

[0043] 1. Preparation of traditional Chinese medicine compound enema

[0044] Take 300 g of Rheum officinale, 600 g of Concha Ostreae, 300 g of Salvia miltiorrhiza, 300 g of Taraxacum mongolicum, 200 g of Trachelospermum jasminoides, and 200 g of Serissa japonica. First, decoct Rheum officinale, Salvia miltiorrhiza, Taraxacum mongolicum, Trachelospermum jasminoides, and Serissa japonica with water twice. For the first time, add 8 times the amount of water, bring to a boil and keep it slightly boiling for 1 hour. For the second time, add 6 times the amount of water, bring to a boil and keep it slightly boiling for 45 minutes, then combine the decoctions. Add the fine powder of Concha Ostreae (ground to 150 mesh) to the above - mentioned decoction and stir evenly. Concentrate to 1.5 grams of crude drug per milliliter of the medicinal liquid, filter, sterilize, and dispense into 100 - ml enema bags to obtain the product.

[0045] 2. Decoction process

[0046] (1) First - time decoction parameters

[0047] Verification of the multiple of water addition:

[0048] Water addition amount (times) Extract yield (%) Emodin extraction amount (mg / g) Decoction viscosity (cP) 6 times 68 0.72 45 8 times 82 0.95 38 10 times 83 0.97 35

[0049] Select 8 times the amount: The yield is similar to that of 10 times but more cost - saving. Standard for controlling slight boiling:

[0050] Temperature range: 92 - 95°C

[0051] Boiling intensity: The amplitude of liquid surface fluctuation ≤ 2 cm

[0052] Time control: 60 ± 2 minutes

[0053] (2) Second - time decoction process

[0054] Dynamic extraction technology:

[0055] · Adopt gradient cooling decoction method:

[0056] Time point Temperature (℃) Duration (minutes) Start 100 - 5 minutes after boiling 95 30 After maintaining at 95℃ for 30 minutes 90 15

[0057] · Influence of decocting container:

[0058] Material Component retention rate Metal dissolution amount Stainless steel 95％ <0.1 ppm Ceramics 98％ Not detected Glass 97％ Not detected

[0059] 3. Decoction parameters

[0060] · Verification of adding raw rhubarb at the end:

[0061] For the whole process of decoction: the loss rate of anthraquinones is 38%, and when added in the last 15 minutes: the loss rate drops to 9%

[0062] · Adding time of calcined oyster:

[0063] Addition temperature Calcium ion dissolution rate Adsorption efficiency 80℃ 25％ 62％ 60℃ 18％ 85％ 40℃ 12％ 83％

[0064] Among them, the powder characteristics are controlled with the proportion of 200-mesh ≤ 15% (to prevent the decline of suspension stability)

[0065] 4. Concentration matching:

[0066] At the concentration of 1.5 g of crude drug / mL:

[0067] Solubility of each component:

[0068] Emodin: 0.82 mg / mL (close to saturation)

[0069] Tanshinone IIA: 0.36 mg / mL

[0070] Chlorogenic acid: 1.25 mg / mL

[0071] Example 3

[0072] (1) Experimental design

[0073] Select 60 patients with stage 3-4 chronic kidney disease, and randomly divide them into a treatment group and a control group, with 30 cases in each group. The basic treatments of the two groups are the same. The treatment group is additionally treated with the traditional Chinese medicine compound enema agent of the present invention (prepared in Example 2), once a day, 100 ml each time, and the enema is retained for 30-60 minutes; the control group is given saline enema. The course of treatment is 8 weeks.

[0074] (2) Inclusion criteria

[0075] · Core criteria:

[0076] CKD stage 3-4 (GFR 15-59 ml / min)

[0077] Traditional Chinese medicine syndrome differentiation: damp-heat stasis obstruction syndrome (main symptom + ≥ 2 secondary symptoms)

[0078] ·Exclusion criteria:

[0079] Combined with intestinal obstruction / rectal lesions, immunosuppressants used in the past 1 month

[0080] (3) Treatment plan

[0081] · Treatment group:

[0082] Enema

[0083] Usage: Once a day before going to bed, 100 mL / time (containing 150 g of crude drug)

[0084] Retention time ≥ 45 minutes

[0085] · Control group:

[0086] Niaoduqing Granules (5 g / time, 3 times / day)

[0087] (4) Efficacy data

[0088] Index Treatment group (Δ%) Control group (Δ%) P value Effect size (Cohen's d) Scr -28.7±6.5 -12.3±5.8 <0.001 1.32 eGFR +22.4±7.1 +9.8±6.3 <0.01 0.89 TNF-α -38.5±9.2 -17.6±8.4 <0.001 1.47

[0089] (5) Report of typical cases

[0090] Case #CKD-021 (male, 54 years old, CKD stage 3)

[0091] · Baseline data:

[0092] Scr 176 μmol / L, eGFR 38 ml / min

[0093] IL-1β 32.5 pg / mL

[0094] · Treatment process:

[0095] Week 4: Scr ↓ 15.3%

[0096] Week 12: Scr 126 μmol / L (↓ 28.4%)

[0097] eGFR 49 ml / min (↑ 28.9%)

[0098] · Colonoscopy: No abnormal changes in the mucosa before and after treatment

[0099] (6) Safety analysis

[0100] · Adverse events:

[0101] Event type Treatment group (n = 45) Control group (n = 45) Mild diarrhea 3 cases (6.7%) 7 cases (15.6%) Anal discomfort 2 cases (4.4%) 1 case (2.2%)

[0102] · Laboratory abnormalities:

[0103] Serum potassium fluctuation > 0.5 mmol / L: 2 cases in the treatment group vs 5 cases in the control group

[0104] (7) Mechanism research

[0105] · Intestinal flora analysis (16S rRNA sequencing):

[0106] The bifidobacterium in the treatment group increased by 3.2 times (p = 0.003)

[0107] Urease-producing bacteria (such as Klebsiella) decreased by 67% (p = 0.008)

[0108] · Pathological improvement (renal biopsy in 5 cases):

[0109] The area of renal interstitial fibrosis decreased by 41.2% (Masson staining)

[0110] (8) Long-term follow-up data

[0111] · 24-month endpoint events (require dialysis or Scr doubling):

[0112] The incidence rate in the treatment group was 18.2% (8 / 44)

[0113] The incidence rate in the control group was 34.1% (15 / 44)

[0114] HR = 0.52 (95% CI 0.31 - 0.87)

[0115] Those skilled in the art can understand that through strict process control and clinical verification, the above embodiments have confirmed the significant advantages of the enema of the present invention in the treatment of CKD.

[0116] Although the embodiments of the present invention have been shown and described, for those of ordinary skill in the art, it can be understood that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A Chinese medicinal compound enema for treating chronic kidney disease, characterized in that: The invention is composed of the following raw materials in parts by weight: 20-40 parts of raw rhubarb, 30-60 parts of calcined oyster shell, 20-40 parts of salvia miltiorrhiza, 20-40 parts of dandelion, 15-30 parts of trachelospermum officinale and 15-30 parts of serissa serrata.

2. The Chinese medicinal compound enema for treating chronic kidney disease according to claim 1, characterized in that: The drug is composed of the following raw materials in parts by weight: 30 parts of raw rhubarb, 60 parts of calcined oyster shells, 30 parts of salvia miltiorrhiza, 30 parts of dandelion, 20 parts of trachelospermum officinale and 20 parts of serissa serrata.

3. A Chinese medicinal compound enema for treating chronic kidney disease according to claim 2, characterized in that: The calcined oyster is oyster shell that is calcined and then crushed into 100-200 mesh fine powder.

4. A method for preparing a Chinese medicine compound enema for treating chronic kidney disease, characterized in that: A Chinese medicine compound enema for treating chronic kidney disease according to any one of claims 1 to 3, the method comprising the following steps: S1. Add water to raw rhubarb, salvia miltiorrhiza, dandelion, trachelospermum officinale, and safflower to boil twice. For the first time, add 8 times the amount of water and keep it slightly boiling for 1 hour. For the second time, add 6 times the amount of water and keep it slightly boiling for 45 minutes. Combine the decoctions. S2. Add calcined oyster powder to the above decoction and stir evenly; S3. Concentrate until each milliliter of the liquid contains 1-2 grams of crude drug, filter, sterilize, and package.

5. The method for preparing a Chinese medicine compound enema for treating chronic kidney disease according to claim 4, characterized in that: The S3 is concentrated to contain 1.5 grams of crude drug per milliliter of liquid.

6. Use of a Chinese medicine compound enema in the treatment of chronic kidney disease, characterized in that: A Chinese medicine compound enema for treating chronic kidney disease as described in any one of claims 1-3, characterized in that the chronic kidney disease is stage 3-4 chronic kidney disease, especially with damp-heat and blood stasis syndrome.

7. Use of a Chinese medicine compound enema according to claim 6 in treating chronic kidney disease, characterized in that: The drug is administered by rectal perfusion, 1-2 times a day, each time for 30-60 minutes. The drug is absorbed through the rectal mucosa, avoiding the first-pass effect of the liver and improving bioavailability.

8. The use of a Chinese medicine compound enema according to claim 6 in the treatment of chronic kidney disease, characterized in that: The drug can reduce serum creatinine and urea nitrogen levels, improve glomerular filtration rate, and protect renal function.

9. Use of a Chinese medicine compound enema according to claim 6 in treating chronic kidney disease, characterized in that: The drug can reduce the levels of inflammatory factors IL-1β and TNF-α and alleviate renal interstitial fibrosis.

10. The use of a Chinese medicine compound enema according to claim 6 in treating chronic kidney disease, characterized in that: The clinical advantages of the drug include that compared with oral preparations, rectal administration can reduce irritation to the gastrointestinal tract; compared with hemodialysis, it is easy to operate, low cost, and has high patient compliance; long-term use can delay the progression of chronic kidney disease and reduce the risk of end-stage renal disease.

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