A traditional Chinese medicine compound suppository for treating diabetic nephropathy and a preparation method thereof

Abstract

The application belongs to the field of medicine, and particularly relates to a traditional Chinese medicine compound suppository for treating diabetic nephropathy and a preparation method thereof. The traditional Chinese medicine compound for treating diabetic nephropathy comprises the following components in parts by weight: 15-30 parts of verbena, 30-60 parts of astragalus, 10-20 parts of siler, 10-20 parts of notopterygium, 15-60 parts of caulis spathulatae, 15-60 parts of giant knotweed, 10-30 parts of yizhi, 15-30 parts of acer truncatum batal, 15-30 parts of pteridium aquilinum, and 3-10 parts of borneol. The compound liver portal suppository prepared from the traditional Chinese medicine compound can treat the root and the branch, can significantly improve kidney function, can improve various clinical indexes of patients with diabetic nephropathy, and has a significant treatment effect.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of medicine, and particularly relates to a traditional Chinese medicine compound suppository for treating diabetic nephropathy and a preparation method thereof. BACKGROUND

[0002] At present, the drugs for treating diabetic nephropathy in modern medicine are mainly oral drugs, injection drugs and external application drugs. The oral drugs are affected by many factors, including the stimulation to gastric mucosa, the influence of liver first-pass effect on the absorption rate of the drugs, and the inactivation due to the destruction of gastrointestinal pH or enzymes. When the drugs are orally administered, the intake of food also affects the absorption of the drugs, and the oral western medicine may cause drug eruptions. The above problems confuse doctors and patients. In addition to oral drugs, the use of injection drugs also has certain risks and clinical problems such as patient resistance. At present, the treatment of diabetic nephropathy in traditional Chinese medicine mainly uses traditional oral Chinese medicine or Chinese patent medicine, and in some hospitals, decoction rectal instillation is used for treatment. The oral Chinese medicine decoction or Chinese patent medicine has the problems of difficult taste and color correction, and needs to be absorbed by the gastrointestinal tract. There are also problems such as the stimulation to the gastrointestinal mucosa as described above. The rectal instillation has complex operation and is relatively resistant to patients.

[0003] Suppository is one of the ancient dosage forms, and is also called "plug medicine" and "sitting medicine" in traditional Chinese medicine. The records about the treatment of diseases by suppository can be traced back to "Shiji · Bian Que Canggong Biography" in the Eastern Han Dynasty, "Shanghan Lun" by Zhang Zhongjing in the Eastern Han Dynasty, "Zhujiaoyuji" by Ge Hong in the Jin Dynasty, and "Qianjin Fang" by Sun Simiao in the Tang Dynasty. Most traditional Chinese medicines are bitter and difficult to swallow, and some traditional Chinese medicines may cause nausea, vomiting and other phenomena after being taken, which brings discomfort to patients. Compared with traditional oral administration of traditional Chinese medicine and western medicine, suppository can avoid the influence of drug odor on patients through rectal administration. Suppository has good operability compared with traditional Chinese medicine decoction and western medicine injection, is simple to carry and use.

[0004] Diabetic nephropathy is a common chronic microvascular complication of diabetes. Its primary clinical manifestations include polydipsia, polyphagia, polyuria, and weight loss. While mild cases may present with no obvious symptoms, advanced stages often include cardiovascular and retinal pathology. In the early stages of diabetic nephropathy, increased glomerular filtration rate (GFR) and GFR (glomerular filtration fraction) lead to polyuria. Proteinuria is the primary clinical manifestation of diabetic nephropathy and can persist from the early stages until organic renal changes occur. Water intake is crucial in maintaining fluid balance in patients with diabetic nephropathy and is crucial in dietary care. Since oliguria or anuria may occur in the uremic stage of end-stage renal disease, excessive water intake can increase the burden on the kidneys and worsen the condition. Therefore, fluid intake should be carefully controlled for patients in this stage. Using suppositories to administer medication reduces the additional water intake associated with conventional oral medications, facilitating the controlled regulation of fluid intake in patients with late-stage diabetic nephropathy.

[0005] Based on the above reasons, the development of traditional Chinese medicine suppositories for diabetic nephropathy has positive therapeutic significance for the treatment of diabetic nephropathy. Summary of the Invention

[0006] The invention provides a traditional Chinese medicine compound rectal suppository for treating diabetic nephropathy and a preparation method thereof. The suppository can be administered through the rectum and is easy to carry and use.

[0007] The technical solution of the present invention is achieved as follows:

[0008] A traditional Chinese medicine compound for treating diabetic nephropathy comprises the following components in parts by weight: 15-30 parts of verbena, 30-60 parts of astragalus, 10-20 parts of siler, 10-20 parts of notopterygium wilfordii, 15-60 parts of millettia repens, 15-60 parts of knotweed, 10-30 parts of alpinia oxyphylla, 15-30 parts of scutellaria baicalensis, 15-30 parts of phragmites australis, and 3-10 parts of borneol.

[0009] Furthermore, the Chinese medicine compound comprises the following components in parts by weight: 20 parts of verbena, 50 parts of astragalus, 15 parts of siler, 15 parts of notopterygium wilfordii, 40 parts of millettia reticulata, 40 parts of knotweed, 20 parts of alkyl oxyphylla, 20 parts of smilax glabra, 20 parts of phragmites australis, and 5 parts of borneol.

[0010] A method for preparing a traditional Chinese medicine compound for treating diabetic nephropathy comprises the following steps:

[0011] Take the formulated amounts of verbena, astragalus, siler, angelica dahurica, millettia reticulata, knotweed, alpinia oxyphylla, oxalis, and phoenix tail grass, crush them, add water to boil, filter, and concentrate the filtrate to obtain a medicinal concentrate. The weight ratio of the medicinal concentrate to the total weight of the added medicinal materials is 3:1, and then add the formulated amount of borneol to obtain a medicinal concentrate juice.

[0012] Furthermore, the medicinal materials are crushed and passed through an 80-mesh sieve; the amount of water added is 9 times the weight of the medicinal materials; and the filter used is an 800-mesh filter.

[0013] Application of the above-mentioned Chinese herbal compound in the preparation of a medicament for treating diabetic nephropathy.

[0014] Furthermore, the medicine is a suppository.

[0015] A traditional Chinese medicine compound anal suppository for treating diabetic nephropathy contains the traditional Chinese medicine compound.

[0016] Furthermore, the Chinese herbal compound rectal suppository comprises the following components: the above-mentioned concentrated drug juice, a suppository base and honey; the weight ratio of the concentrated drug juice to the honey is 1:1.5.

[0017] A method for preparing a traditional Chinese medicine compound anal suppository for treating diabetic nephropathy comprises the following steps:

[0018] (1) Take the formulated amount of pure honey, heat it on low heat until the honey foams, add the drug concentrate, stir constantly and continue heating until the drug honey drops into beads and becomes silky, thus obtaining the drug concentrate; place the suppository matrix in a water bath to melt it to form a colorless and transparent blank matrix solution, pour it into the suppository mold, and fill the mold gap until it does not overflow; after filling, let it stand at 20-25°C for 1-2 minutes, and turn the mold upside down to allow the uncondensed matrix in the center to flow out, forming a cavity;

[0019] (2) Fill the cavity with drug concentrate, then inject the blank matrix into the plug mold, seal the tail, wait for about 30 minutes, let the matrix cool, cut off the overflow part, and demold.

[0020] Furthermore, the suppository base is fatty acid glyceride, the water bath temperature is controlled at 50° C., and the specification of the suppository mold is a 1.5 g bullet-shaped suppository mold.

[0021] The application of the traditional Chinese medicine compound rectal suppository in preparing medicine for treating diabetic nephropathy.

[0022] Furthermore, in the application, the compound suppository is inserted 2-3 cm into the anus, 4 suppositories are taken per day, divided into 3 times, 1 suppository each in the morning and noon, and 2 suppositories in the evening.

[0023] Furthermore, in the application, the Chinese herbal compound rectal suppository is used together with valsartan.

[0024] Beneficial effects of the present invention:

[0025] The pathogenesis of diabetic nephropathy hinges on a deficiency of the body's vital energy and the retention of pathogenic factors, a situation characterized by underlying deficiency and superficial excess. In the early stages of diabetic nephropathy, kidney qi deficiency and blood stasis persist throughout the disease, acting as key factors in its development and progression.

[0026] Most patients with diabetic nephropathy suffer from irregular diet and overeating of sweet and greasy foods, which leads to dysfunction of the spleen and stomach, thus producing dampness and phlegm, accompanied by wind evil, which accumulates and turns into heat, hiding and dormant. Over time, the stagnant heat damages yin and consumes qi, and the blood turns into blood stasis; the blood stasis blocks the kidney, and the kidney's function of opening and closing is abnormal, resulting in the loss of essence and qi and the discharge, forming proteinuria; the blood stasis hinders the kidney's gasification, and the kidney's function of controlling water cannot be normally exerted, so edema occurs; body fluids and blood have the same origin, and after blood stasis, the body fluids do not flow smoothly and phlegm is produced. Phlegm diseases are related to blood, and blood diseases are related to phlegm. Phlegm and blood stasis are intertwined and penetrate each other, the collaterals are blocked, qi is damaged and yin is consumed, and both qi and yin deficiency lead to the occurrence of diabetic nephropathy.

[0027] This product uses Alpinia oxyphylla and Astragalus membranaceus to warm the spleen and kidney, consolidate essence and reduce urination, replenish qi and raise yang, and restore the kidney's gasification function to treat the root cause; uses Millettia reticulata to promote blood circulation and remove blood stasis, and uses Polygonum cuspidatum and Verbena officinalis to eliminate dampness and purge turbidity, jointly targeting the pathogenesis of phlegm and blood stasis blocking the collaterals in diabetic nephropathy; uses Saposhnikovia divaricata, Notopterygium wilfordii, and Acer truncatum to dispel wind and relieve pain, jointly targeting the symptoms of diabetic nephropathy with kidney deficiency and wind; and uses Pteris parviflora to reduce swelling and detoxify, reduce inflammation and promote diuresis, and activate collaterals and relieve pain. Finally, it is combined with borneol to accelerate drug absorption, accelerate the entry of other drugs into the blood, increase the cool and comfortable feeling of the drugs during use, and relieve discomfort during use. The above-mentioned drugs in this product are used together to treat both the symptoms and the root cause. When used in combination with valsartan, it can significantly improve renal function and improve various clinical indicators of patients with diabetic nephropathy, and has a significant therapeutic effect on diabetic nephropathy.

[0028] Modern research indicates that Polygonum cuspidatum can improve renal function, reduce BUN and Scr levels in patients with diabetic nephropathy, and protect the kidneys from various diseases, including renal ischemia-reperfusion injury in the late stages of diabetic nephropathy. In addition to its heat-clearing, detoxifying, and blood stasis-relieving properties, Polygonum cuspidatum also has excellent laxative and heat-purging properties. It can accelerate intestinal peristalsis, increase bowel movements, promote toxin excretion, and reduce proteinuria, thereby improving symptoms and alleviating kidney damage. Pteris viridis, a Hainan specialty herb, clears heat, dampness, and toxins, while also promoting diuresis and protecting the kidneys, preventing and treating diabetic nephropathy. It can also reduce proteinuria, protect renal function, and inhibit or delay the progression of renal damage. Modern pharmacological experiments have also shown that Pteris viridis has excellent hypoglycemic properties. Niu Er Feng (Acer niger) dispels wind, relieves pain, clears heat, detoxifies, promotes blood circulation, removes blood stasis, and reduces swelling and pain. It primarily contains flavonoids such as rutin and quercetin, as well as several alkaloids. Among them, rutin is a widely distributed flavonoid compound that is slightly soluble in water but soluble in hot water and ethanol. It has anti-inflammatory, antiviral and aldose reductase inhibitory effects and is a good medicine for treating diabetes, hypertension, cardiovascular disease and many other diseases.

[0029] Furthermore, hollow suppositories made with the traditional Chinese medicine compound described herein have an outer shell made of a pure matrix, while the hollow core can be filled with drugs in various states, including solid, liquid, and suspended. Compared to conventional suppositories, hollow suppositories offer numerous advantages, including high dissolution, rapid drug release, high bioavailability, and excellent formulation stability. Rapid or sustained release can also be achieved by adding appropriate excipients to the drug in the hollow suppository's core or by formulating the drug into a solid dispersion. The hollow suppository preparation method employed in the present invention offers advantages over other suppositories, including rapid drug release, rapid onset of action, and high bioavailability. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0031] Figure 1 The HE staining results of rabbit kidneys in each group (X400). DETAILED DESCRIPTION

[0032] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making any creative efforts shall fall within the scope of protection of the present invention.

[0033] Example 1

[0034] A traditional Chinese medicine compound for treating diabetic nephropathy comprises the following components in parts by weight: 20 parts of verbena, 50 parts of astragalus, 15 parts of siler, 15 parts of notopterygium wilfordii, 40 parts of millettia repens, 40 parts of knotweed, 20 parts of alpinia oxyphylla, 20 parts of smilax china, 20 parts of phragmites australis, and 5 parts of borneol.

[0035] A method for preparing a traditional Chinese medicine compound for treating diabetic nephropathy comprises the following steps:

[0036] Take the formulated amount of verbena, astragalus, siler, angelica root, millettia reticulata, polygonum cuspidatum, alpinia oxyphylla, oxalis, and phoenix tail grass, ultrafinely grind them through an 80-mesh sieve, add 9 times the weight of the medicinal materials in water and boil them twice, filter through an 800-mesh filter, and concentrate the filtrate to obtain a medicinal concentrate, the weight of which is 3 times the weight of the medicinal materials; then add the formulated amount of borneol to obtain a medicinal liquid concentrate.

[0037] Example 2

[0038] A traditional Chinese medicine compound for treating diabetic nephropathy comprises the following components in parts by weight: 15 parts of verbena, 30 parts of astragalus, 10 parts of siler, 10 parts of notopterygium wilfordii, 15 parts of millettia repens, 15 parts of knotweed, 10 parts of alkyl oxyphylla, 15 parts of scutellaria baicalensis, 15 parts of phragmites australis, and 3 parts of borneol.

[0039] The preparation method is the same as that in Example 1.

[0040] Example 3

[0041] A traditional Chinese medicine compound for treating diabetic nephropathy comprises the following components in parts by weight: 30 parts of verbena, 60 parts of astragalus, 20 parts of siler, 20 parts of notopterygium wilfordii, 60 parts of millettia repens, 60 parts of knotweed, 30 parts of alpinia oxyphylla, 30 parts of scutellaria baicalensis, 30 parts of phragmites australis, and 10 parts of borneol.

[0042] The preparation method is the same as that in Example 1.

[0043] Example 4

[0044] A traditional Chinese medicine compound rectal suppository for treating diabetic nephropathy comprises the drug concentrate prepared in any one of Examples 1 to 3, a suppository base, and honey; the weight ratio of the drug concentrate to the honey is 1:1.5.

[0045] The preparation method thereof comprises the following steps:

[0046] (1) Take the formulated amount of pure honey, heat it on low heat until the honey foams, add the drug concentrate, stir constantly and continue heating until the drug honey drops into beads and becomes silky, thus obtaining the drug concentrate; place the suppository matrix in a water bath to melt it to form a colorless and transparent blank matrix solution, pour it into the suppository mold, and fill the mold gap until it does not overflow; after filling, let it stand at 20-25°C for 1-2 minutes, and turn the mold upside down to allow the uncondensed matrix in the center to flow out, forming a cavity;

[0047] (2) Fill the cavity with drug concentrate, then inject the blank matrix into the plug mold, seal the tail, wait for about 30 minutes, let the matrix cool, cut off the overflow part, and demold.

[0048] In this embodiment, the suppository base is fatty acid glyceride, the water bath temperature is controlled at 50° C., and the specification of the suppository mold is a 1.5 g bullet-shaped suppository mold.

[0049] The Chinese medicine compound anal suppository prepared in this embodiment can be used directly to treat diabetic nephropathy. During treatment, the compound suppository is inserted into the anus 2-3 cm, 4 tablets per day, divided into 3 times, 1 tablet each in the morning and noon, and 2 tablets in the evening.

[0050] Comparison of the effects of different drug combinations on diabetic nephropathy

[0051] 1. Experimental Materials

[0052] (1) Experimental animals

[0053] Thirty-five male SPF Japanese large-eared white rabbits, weighing 2.4 ± 0.2 kg, were purchased from the Laboratory Animal Center of the Hainan Provincial Center for Disease Control and Prevention and housed there under conditions of suitable temperature and relative humidity. This animal study adhered to the guidelines of the World Medical Association's Declaration of Helsinki for the care and use of experimental animals. A total of 35 rabbits were used for all experiments.

[0054] Rearing environment: The animals were kept in cages in a clean animal room, in a standard environment with a 12-hour light cycle and no adverse stimulation except for the experiment.

[0055] Animal feed: Ordinary feed was purchased from the Experimental Animal Center of Shandong University of Traditional Chinese Medicine, and solid feed and bedding were purchased from the Lukang Experimental Animal Center.

[0056] (2) Modeling method

[0057] 1. Diabetes Model Construction

[0058] Thirty Japanese white rabbits weighing 2.4 ± 0.2 kg (Group A, untreated rabbits) were injected with 100 mg / kg of alloxan into the ear vein on an empty stomach. Blood glucose levels were monitored continuously for 24 hours to prevent hypoglycemia. After 72 hours, fasting blood glucose levels were measured. Animals with fasting blood glucose levels above 16.7 mmol / L were considered to have successfully established a diabetes model.

[0059] 2. Construction of diabetic nephropathy model

[0060] After the successful establishment of the diabetic nephropathy model, the rats were first fed a high-fat diet (1% cholesterol + 4% lard), fasting blood glucose was maintained at ≥16.7 mmol / L, urine volume was >150% of the original urine volume, and urine protein appeared for more than two consecutive weeks (24h urine protein qualitative: positive; quantitative: greater than 50% of the normal group), confirming that the diabetic nephropathy model was successful.

[0061] (3) Suppository preparation

[0062] 1. Bolt mold production

[0063] Melt the fatty acid glyceride in a 50°C water bath to form a colorless, transparent blank matrix solution. Pour the solution into a 1.5g bullet-shaped plug mold until the mold is completely filled without overflowing. About 1 minute after filling (room temperature 25°C), invert the mold to allow the unsolidified matrix in the center to flow out, forming a cavity.

[0064] 2. Filling concentrated medicine (contents) production

[0065] The Chinese medicine required for the experiment was prepared into a drug concentrate according to the method of Example 1; then, referring to the method of Example 4, honey was added to prepare the suppository contents. In this experiment, a total of 5 different suppository contents were prepared, and the drug composition ratios of each group were as follows:

[0066] (1) Composition of Suppository C:

[0067] Group C1: Verbena officinalis 20g, Astragalus 50g, Saposhnikovia divaricata 15g, Notopterygium wilfordii 15g, Millettia repens 40g, Polygonum cuspidatum 40g, Alpinia oxyphylla 20g, Acer palmatum 20g, Herba Pteris 20g, Borneolum bungeana 5g;

[0068] Group C2: Verbena officinalis 15g, Astragalus membranaceus 30g, Saposhnikovia divaricata 10g, Notopterygium wilfordii 10g, Millettia reticulata 15g, Polygonum cuspidatum 15g, Alpinia oxyphylla 10g, Acer palmatum 15g, Herba Pteris 15g, Borneolum bungeana 3g;

[0069] C3: Verbena 30g, Astragalus 60g, Saposhnikovia divaricata 20g, Notopterygium wilfordii 20g, Millettia reticulata 60g, Polygonum cuspidatum 60g, Alpinia oxyphylla 30g, Acer truncatum 30g, Herba Pteris multiflora 30g, and Borneol 10g.

[0070] (2) Contents of suppository D: Verbena 20g, Alpinia oxyphylla 20g, Acer truncatum 20g, and Herba Pteris 20g.

[0071] (3) Contents of suppository E: Millettia reticulata 40g, Polygonum cuspidatum 40g, Borneolum Syntheticum 5g, Astragalus 50g, Notopterygium incisum 15g, Saposhnikovia divaricata 15g.

[0072] 3. Bolt mold pouring and sealing

[0073] According to experimental requirements, the five different suppositories were prepared. The cavity was filled with different drug concentrates, and then a colorless blank matrix was injected into the suppository mold. The tail was sealed by melting. After waiting for about 30 minutes, the matrix cooled, the excess was trimmed, and the suppository was demolded.

[0074] (IV) Model grouping

[0075] This experiment was divided into 7 groups: Group A (blank control group); Group B (model group); Group C (suppository C1, C2, and C3 intervention group); Group D (suppository D intervention group); and Group E (suppository E intervention group).

[0076] Group A used rabbits without modeling, and the other groups used rabbits with diabetic nephropathy model.

[0077] (V) Method of administration

[0078] 1. Group A: No medication was given, and the subjects drank water and ate normally;

[0079] 2. Group B: No drugs were given, and the subjects drank water and ate normally;

[0080] Groups C1-C3 were given suppositories C1, C2, and C3, respectively, for rectal insertion, four times daily, divided into three doses: one suppository each in the morning and afternoon, and two suppositories in the evening. They were also given valsartan 10 mg / kg / day.

[0081] 6. Group D: Administer suppository D for rectal insertion, 4 times a day, divided into 3 doses: 1 suppository each in the morning and afternoon, and 2 suppositories in the evening; concurrently receive valsartan 10 mg / (kg·d);

[0082] 7. Group E: Administer suppository E for rectal insertion, 4 times a day, divided into 3 doses: 1 suppository each in the morning and afternoon, and 2 suppositories in the evening; concurrently receive valsartan 10 mg / (kg·d);

[0083] Dosing duration: 8 weeks.

[0084] 3. Observation indicators and experimental results

[0085] After the drug administration was completed, the test indicators and results were as follows:

[0086] 1. Fasting blood glucose (FBG), U-mAlb, serum creatinine (Scr), and blood urea nitrogen (BUN) levels

[0087] Specific procedures: After collecting urine for 8 hours, the urine was weighed and blood was collected from the retroorbital venous capillary tube. After standing, the blood was centrifuged at 3500 rpm for 10 minutes, and serum was collected for later use. Following the kit instructions, fasting blood glucose (FBG), urine microalbumin (U-mAlb), serum creatinine (Scr), and blood urea nitrogen (BUN) levels were measured in each group. The results are shown in Table 1.

[0088] Table 1 Comparison of test indicators of animals in each group (n=5, )

[0089]

[0090]

[0091] Note: Compared with group A, *P<0.05; compared with group B, △ P<0.05; compared with group C (including C1, C2, and C3), # P<0.05.

[0092] The results in Table 1 show:

[0093] Compared with group A, the FBG, U-mAlb, SCr, and BUN of rabbits in group B were significantly increased (P<0.05), indicating that the model was successfully established.

[0094] Compared with Group B, FBG, U-mAlb, SCr, and BUN levels in Groups C1, C2, and C3 were significantly lower (P < 0.05), indicating that the suppositories in Groups C1, C2, and C3 all have a certain therapeutic effect on diabetic nephropathy. FBG, U-mAlb, SCr, and BUN levels in Groups D and E were lower than in Group B, but the differences were not statistically significant (P > 0.05), indicating that the efficacy of the separate formula groups D and E was not significant. There were no significant differences in any of the data between Groups C1, C2, and C3 (P > 0.05), indicating that the suppositories described in the three examples of the present invention are stable and that there are no significant differences between the examples. Compared with Group C (including Groups C1, C2, and C3), there were significant differences in the separate formula groups D and E (#P < 0.05), indicating that the efficacy of Group C was significantly improved.

[0095] 2. Kidney Tissue Pathological Staining

[0096] Specific operation: The left kidney of the rabbit was cut longitudinally, fixed in 10% paraformaldehyde, dehydrated, transparent, and embedded in paraffin before sectioning to a thickness of about 2 to 3 μm for HE staining. Figure 1 shown.

[0097] After 8 weeks of treatment, the kidney tissues of rabbits in each group were stained with HE and the pathological changes were observed under light microscope as follows ( Figure 1 ):

[0098] The morphology of glomeruli, mesangium, renal capsule and renal tubules in the normal group (group A) were basically normal.

[0099] In the model group (Group B), rabbits showed nodular glomerulosclerosis and some atrophy, with enlarged renal capsules, increased mesangial matrix, thickened and widened mesangium, and nodular hyperplasia, partial dilatation of renal tubules, and vacuolar degeneration of renal tubular epithelial cells, indicating successful modeling.

[0100] Compared with the model group (Group B), the above pathological changes in renal tissue of each treatment group were alleviated to varying degrees; the changes were most obvious in Groups C1, C2, and C3, with only focal glomerular mesangial matrix hyperplasia and segmental hyperplasia in some glomeruli. There was no significant difference among Groups C1, C2, and C3. Figure 1 The middle image is of Group C1. Groups D and E showed more pronounced glomerular mesangial nodular hyperplasia than Group C, but milder than Group B. This suggests that renal tissue lesions in Groups D and E also improved to some extent, but the effect was less pronounced than in Group C.

[0101] In summary, the results of this experimental study demonstrate that this formula has the effects of lowering blood sugar, reducing urinary microprotein leakage, and improving renal pathology. Its effects are not only significantly higher than those in the model group B, but also significantly higher than those in the separated formula groups D and E. This indicates that the rational combination of this formula and valsartan significantly enhances its effects in lowering blood sugar, reducing urinary microprotein leakage, and improving renal pathology.

[0102] Clinical efficacy experiment of the Chinese medicine compound suppository of the present invention

[0103] (1) General Information

[0104] From January 2019 to December 2020, patients who met the diagnostic criteria for diabetic nephropathy were selected. Western medicine diagnostic criteria were consistent with the diagnostic criteria for diabetes in the "Guidelines for the Prevention and Treatment of Diabetes in China," and Traditional Chinese Medicine diagnostic criteria were consistent with the relevant diagnostic criteria for early diabetic nephropathy in the "Routine Diagnosis and Treatment of Internal Medicine Diseases in Traditional Chinese Medicine." The 60 patients included in this study were admitted to the First Affiliated Hospital of Hainan Medical University between February 2019 and February 2020. All met the diagnostic criteria for diabetic nephropathy, had good medication compliance, and were able to persist in treatment. The study was approved by the Ethics Committee of Hainan Medical University, and the patients and their families signed informed consent.

[0105] The experimental group included 36 males and 24 females, aged 45 to 73 years (mean, 56.71 ± 5.38) years, with a disease duration of 3 to 18 years (mean, 6.87 ± 1.28) years. The patients were randomly divided into two groups of 30 patients each using the block randomization principle. The control group included 16 males and 14 females, aged 45 to 72 years (mean, 56.65 ± 5.35) years, with a disease duration of 3 to 18 years (mean, 6.83 ± 1.25) years. The experimental group included 20 males and 10 females, aged 45 to 73 years (mean, 56.77 ± 5.41) years, with a disease duration of 3 to 18 years (mean, 6.91 ± 1.31) years. General data, including age and disease duration, were clinically comparable between the two groups (P > 0.05).

[0106] (2) Treatment methods:

[0107] 1. Basic treatment

[0108] (1) Lifestyle intervention: diabetic diet (calorie control, balanced nutrition, low-fat and low-salt, high-quality protein diet), moderate physical activity, and diabetes education.

[0109] (2) Hypoglycemic: Oral hypoglycemic drugs are used to control blood sugar. When the control is poor, insulin is added and the dosage of insulin is adjusted according to the blood sugar level to stabilize blood sugar.

[0110] (3) Antihypertensive and lipid-lowering treatments: Choose treatments that do not interfere with this experiment.

[0111] 2. Control group: In addition to baseline treatment, patients received valsartan capsules (80 mg once daily). Take with warm water. Specification: 80 mg / tablet. Approval number: National Medicine Standard H20040217. Manufacturer: Beijing Novartis Pharmaceuticals Co., Ltd.

[0112] 3. Treatment Group: Compound Suppository Group: Patients in the experimental group received the compound suppository prepared in Example 1 in addition to the control group. Rectal administration was performed by inserting the suppository 2-3 cm into the anus with the index finger while wearing a disposable fingertip. Four suppositories were administered daily, divided into three doses: one in the morning and one at noon, and two in the evening. Valsartan capsules (80 mg) were also administered once daily. The suppositories were taken with warm water. Specifications: 80 mg / tablet. Approval Number: National Medicine Standard H20040217. Manufacturer: Beijing Novartis Pharmaceutical Co., Ltd.

[0113] Treatment course: Both groups of patients received treatment for 8 weeks.

[0114] (3) Testing indicators

[0115] 1. General vital signs testing: blood pressure, heart rate, body temperature, and pulse.

[0116] 2. Efficacy indicators

[0117] Fasting blood glucose (FPG), glycosylated hemoglobin (bAlc), blood lipids (TG, TC, HDL-C, LDL-C), renal function (BUN, Scr), and 24h urine protein.

[0118] 3. Efficacy evaluation criteria

[0119] Refer to the "Diagnosis, Syndrome Differentiation and Therapeutic Efficacy Evaluation Criteria for Diabetic Nephropathy (Trial Scheme)"

[0120] Markedly effective: Urinary microalbumin excretion rate or urine protein quantitative reduction ≥ 50%, or normal.

[0121] Effective: Urinary microalbumin excretion rate or urine protein quantity is reduced by ≥30%, but less than 50%.

[0122] Invalid: Those who do not meet the above validity standards.

[0123] (4) Statistical methods

[0124] All data were analyzed using SPSS 17.0 software and expressed as mean ± standard deviation. Continuous data were analyzed using the t-test (independent t-test for comparisons between groups and paired t-test for comparisons within groups), enumeration data using the chi-square test, and ordinal data using the rank-sum test. P values ​​greater than 0.05 were considered statistically insignificant, P values ​​less than 0.05 were considered statistically significant, and P values ​​less than 0.01 were considered statistically significant.

[0125] (V) Results

[0126] 1. Comparison of clinical efficacy between the two groups of patients after treatment

[0127] Table 2 Comparison of clinical efficacy between the two groups of patients after treatment

[0128]

[0129] Note: Compared with the control group, *P<0.05

[0130] As can be seen from Table 2, the number of effective patients and the effective rate in the treatment group were significantly different from those in the control group, indicating that the suppository of the present invention combined with valsartan has a significant effect on diabetic nephropathy, and the effect is significantly higher than that of valsartan capsules.

[0131] 2. Comparison of FPG between the two groups before and after treatment

[0132] Table 3 Comparison of FPG (mmol / L) between the two groups before and after treatment

[0133]

[0134] Note: Compared with the treatment group before treatment: *P<0.05; compared with the control group after treatment: ▲ P<0.05.

[0135] As can be seen from Table 3, after using the suppository of the present invention, the patient's FPG significantly decreased, and there was also a significant difference compared to the control group after treatment. The suppository of the present invention can significantly reduce the patient's FPG, and there is a significant difference compared to the control group after treatment and the treatment group before treatment. This shows that the suppository of the present invention is used in combination with valsartan, and its therapeutic effect is significant, and is significantly higher than the valsartan capsule of the control group.

[0136] 3. Comparison of HbAlc between the two groups before and after treatment

[0137] Table 4 Comparison of HbA1c (%) before and after treatment

[0138]

[0139] Note: Compared with before treatment: *P<0.05; compared with the control group after treatment: ▲ P<0.05.

[0140] As can be seen in Table 4, the combined use of the suppositories of the present invention and valsartan significantly reduced patients' HbA1c levels, with significant differences also observed compared to the control group. This indicates that the suppositories of the present invention can significantly reduce patients' HbA1c levels, with significant differences observed both after treatment in the control group and before treatment in the treatment group. Therefore, the combined use of the suppositories of the present invention and valsartan is highly effective, significantly exceeding that of valsartan capsules alone.

[0141] 4. Changes in blood lipids in the two groups of patients before and after treatment

[0142] Table 5 Comparison of blood lipids (mmol / L) before and after treatment

[0143]

[0144] Note: Compared with before treatment: *P<0.05; compared with the control group after treatment: ▲ P<0.05.

[0145] As can be seen from Table 5, after using the suppository of the present invention, the TG and TC in the blood lipids of the patients were significantly reduced, and there was also a significant difference compared with the control group after treatment.

[0146] After using the suppository of the present invention, the HDL-C in the patients' blood lipids increased significantly, while the LDL-C decreased significantly, and there was a significant difference compared with the control group.

[0147] The above data show that the suppositories of the present invention can significantly reduce patients' TG, TC, and LDL-C, and increase patients' HDL-C, with significant differences compared to both the control group after treatment and the treatment group before treatment. Therefore, the suppositories of the present invention, when used in combination with valsartan, have a significant therapeutic effect, and the therapeutic effect is significantly higher than that of valsartan capsules.

[0148] 5. Changes of BU and Scr in the two groups of patients before and after treatment

[0149] Table 6 Comparison of BUN (mmol / L) and Scr (umol / L) before and after treatment

[0150]

[0151]

[0152] Note: Compared with before treatment: *P<0.05; compared with the control group after treatment: ▲ P<0.05.

[0153] As can be seen from Table 6, after using the suppository of the present invention, the patient's BUN and Scr levels were significantly reduced, and there was also a significant difference compared to the control group after treatment. This shows that the suppository of the present invention, when used in combination with valsartan, not only can significantly reduce the patient's BUN and Scr levels, but also has a significantly higher therapeutic effect than the control group. That is, the suppository of the present invention, when used in combination with valsartan capsules, has a significant therapeutic effect, and is significantly higher than valsartan capsules.

[0154] 6. Comparison of 24h urine protein (mg / 24h) between the two groups of patients before and after treatment

[0155] Table 7 24h urine protein (mg / 24h) of the two groups of patients before and after treatment

[0156]

[0157] Note: Compared with before treatment: *P<0.05; compared with the control group after treatment: ▲ P<0.05.

[0158] As can be seen from Table 7, after using suppository of the present invention, patient's 24h urine protein significantly reduces. Compared with control group after treatment, there is also significant difference. Therefore, suppository of the present invention shares with valsartan, can significantly reduce patient's 24h urine protein, and also all has significant difference with control group after treatment. Explain that suppository of the present invention shares with valsartan, not only can significantly reduce patient's 24h urine protein, and action effect is significantly higher than using valsartan capsule alone.

[0159] Based on the above experimental results, the suppository of the present invention, when used in combination with valsartan, has a significant therapeutic effect on diabetic nephropathy, can improve multiple examination indicators of patients, and has a very significant therapeutic effect on diabetic nephropathy. The therapeutic effect is significantly higher than that of valsartan capsules used alone, and the clinical therapeutic effect is very outstanding.

[0160] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A Chinese medicinal compound rectal suppository for treating diabetic nephropathy, characterized in that: The invention is prepared from the following raw materials in parts by weight: 15-30 parts of verbena, 30-60 parts of astragalus, 10-20 parts of siler, 10-20 parts of notopterygium wilfordii, 15-60 parts of millettia repens, 15-60 parts of knotweed, 10-30 parts of alpinia oxyphylla, 15-30 parts of scutellaria baicalensis, 15-30 parts of phragmites australis and 3-10 parts of borneol.

2. The Chinese medicinal compound anal suppository for treating diabetic nephropathy according to claim 1, characterized in that: The invention is prepared from the following raw materials in parts by weight: 20 parts of verbena, 50 parts of astragalus, 15 parts of siler, 15 parts of notopterygium wilfordii, 40 parts of millettia repens, 40 parts of knotweed, 20 parts of alkyl oxyphylla, 20 parts of scutellaria baicalensis, 20 parts of phragmites australis and 5 parts of borneol.

3. The method for preparing a Chinese medicinal compound anal suppository for treating diabetic nephropathy according to claim 1, characterized in that: The following steps are involved: (1) Take the formulated amount of pure honey and heat it on low heat until the honey foams. Add the concentrated drug juice and continue to stir and heat until the honey drops into beads or threads to obtain the concentrated drug juice. Place the suppository matrix in a water bath to melt it to form a colorless and transparent blank matrix solution. Pour it into the suppository mold and fill the mold gap until it does not overflow. After filling, let it stand at 20-25℃ for 1-2 minutes. Turn the mold upside down to allow the uncondensed matrix in the center to flow out, forming a cavity. (2) Fill the cavity with drug concentrate, then inject the blank matrix into the plug mold, seal the tail, wait for 30 minutes, let the matrix cool, cut off the overflow part, and demold; The preparation method of the medicinal concentrated juice comprises the following steps: taking a formulated amount of verbena, astragalus, siler, notopterygium wilfordii, millettia reticulata, polygonum cuspidatum, alpinia oxyphylla, oxalis chinensis, and phoenix tail grass, crushing the powder, boiling the powder with water, filtering and concentrating the powder to obtain a medicinal concentrated solution, and then adding a formulated amount of borneol to obtain the medicinal concentrated juice; the weight ratio of the total weight of the added medicinal materials to the medicinal concentrated solution is 1:

3.

4. The method for preparing a Chinese medicinal compound anal suppository for treating diabetic nephropathy according to claim 3, characterized in that: The weight ratio of the drug concentrate to the honey is 1:1.

5.

5. The method for preparing a Chinese medicinal compound anal suppository for treating diabetic nephropathy according to claim 3, characterized in that: Crush and pass through an 80-mesh sieve; add 9 times the weight of the medicinal material in water, decoct for 25-30 minutes, and decoct twice; use an 800-mesh filter.

6. The method for preparing a Chinese medicinal compound anal suppository for treating diabetic nephropathy according to claim 3, wherein: The suppository base is fatty acid glyceride, and the water bath temperature is controlled at 50°C; the specification of the suppository mold is a 1.5 g bullet-shaped suppository mold.

7. Use of the Chinese medicinal compound rectal suppository according to claim 1 in preparing a medicine for treating diabetic nephropathy.

8. The use according to claim 7, characterized in that: The traditional Chinese medicine compound rectal suppository is used in combination with valsartan capsules.

9. The use according to claim 8, characterized in that Insert the compound suppository 2-3 cm into the anus, 4 suppositories a day, divided into 3 times, 1 each in the morning and noon, and 2 in the evening.

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