CN113244311B

CN113244311B - Pharmaceutical composition for treating cutaneous pruritus after hemodialysis and preparation method thereof

Info

Publication number: CN113244311B
Application number: CN202110571417.3A
Authority: CN
Inventors: 刘子洋; 段连香; 刘伟伟
Original assignee: Individual
Current assignee: Individual
Priority date: 2021-05-25
Filing date: 2021-05-25
Publication date: 2022-07-29
Anticipated expiration: 2041-05-25
Also published as: CN113244311A

Abstract

The invention aims to provide a pharmaceutical composition for treating pruritus cutanea after hemodialysis, which is mainly prepared from the following traditional Chinese medicine raw materials: herba schizonepetae, radix sileris, angelica, salvia miltiorrhiza, moutan bark, fructus kochiae, cortex dictamni, radix sophorae flavescentis, cacumen Tamaricis, raw white paeony root and red paeony root. The pharmaceutical composition can effectively treat and relieve pruritus cutanea appearing in uremia hemodialysis, has low cost and high applicability compared with hemoperfusion and hemodialysis combined treatment, and can be accepted by wide patients. Meanwhile, the pharmaceutical composition has quick response time for treating pruritus cutanea appearing in uremia hemodialysis, can have obvious treatment effect within two weeks, and relieves the pain of patients.

Description

Pharmaceutical composition for treating cutaneous pruritus after hemodialysis and preparation method thereof

Technical Field

The invention relates to the technical field of medicines for treating pruritus in uremia hemodialysis, in particular to a medicine composition for treating skin pruritus after hemodialysis and a preparation method thereof.

Background

Uremic pruritus is one of the most common complications of chronic renal failure maintenance hemodialysis patients. Patients who enter hemodialysis at the end of chronic renal failure gradually increase year by year, and skin itch appears after hemodialysis, with the incidence rate of about 67% -86%, and is more obvious during or after dialysis. The mechanism of occurrence is not completely elucidated, and it is possible that creatinine, urea nitrogen, uric acid, guanidine, phosphate, etc. are degraded from extrarenal routes such as intestinal tract and skin to irritate the skin due to renal failure and failure to discharge from urine, resulting in itching. Pruritus in dialysis patients the degree of pruritus is closely related to factors such as dialysis adequacy, dry skin, hyperhidrosis, pilosebaceous lesions, calcium and phosphorus metabolism disorder, hyperparathyroidism, neuropathy and the like.

At present, no specific treatment method exists, and most western medicines combine hemoperfusion with hemodialysis treatment, although the effect is clear, the cost is high, and common patients cannot bear the treatment method.

Disclosure of Invention

The invention aims to provide a pharmaceutical composition for treating cutaneous pruritus after hemodialysis, which can realize effective treatment on cutaneous pruritus and has low cost and can be borne by patients compared with the existing hemoperfusion and hemodialysis combined treatment.

The invention provides the following technical scheme:

a pharmaceutical composition for treating cutaneous pruritus after hemodialysis, which is mainly prepared from the following traditional Chinese medicine raw materials: herba schizonepetae, radix sileris, angelica, salvia miltiorrhiza, moutan bark, fructus kochiae, cortex dictamni, radix sophorae flavescentis, cacumen Tamaricis, raw white paeony root and red paeony root.

Preferably, the Chinese medicinal raw materials comprise the following components in percentage by mass: 24-36 g of schizonepeta, 26-35 g of divaricate saposhnikovia root, 13-18 g of Chinese angelica, 12-18 g of red-rooted salvia root, 8-12 g of tree peony bark, 24-33 g of belvedere fruit, 25-35 g of dittany bark, 12-17 g of lightyellow sophora root, 12-18 g of cacumen tamaricis, 13-17 g of raw white paeony root and 12-16 g of red paeony root.

Preferably, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 30g of schizonepeta, 30g of divaricate saposhnikovia root, 15g of Chinese angelica, 15g of salvia miltiorrhiza, 10g of tree peony bark, 30g of belvedere fruit, 30g of cortex dictamni, 15g of lightyellow sophora root, 15g of Chinese tamarisk, 15g of raw white paeony root and 15g of red paeony root.

Based on a large amount of experience and theoretical analysis, the inventor of the application believes that the pathogenesis of uremia pruritus is that uremia patients are mainly caused by blood deficiency and wind generation, and damp toxin is stagnated in the striae of skin, so that uremia skin pruritus is caused from the traditional Chinese medicine. Therefore, the inventor obtains the pharmaceutical composition of the application through a large number of screening and combination aiming at the condition that the skin is not nourished, and taking the treatment principles of clearing heat and removing toxicity and dispelling wind and arresting itching as the treatment principles.

The compatibility of the pharmaceutical composition of the present application designed based on the above pathogenesis is as follows:

herba Schizonepetae and radix Saposhnikoviae are used as principal drugs in the formula. Schizonepeta tenuifolia is fragrant and fragrant, has a light smell, warm nature but no dryness, and acts as a dispersing agent, especially dispersing wind-cold in upper energizer but also in blood system, and can disperse stagnated heat in blood system. Fang Feng has a strong smell, warm and moist property, and good at moving upward to treat wind pathogen of upper energizer, but also can move qi system, so it is good at dispelling wind of whole body and can clear damp. Both herbs are pungent in flavor and warm in property and relieving exterior syndrome, and they are indicated for wind-cold all the time, because they are combined with each other as a pair of herbs and reinforce each other and go upward to disperse wind-cold, enhance the action of dispelling wind-dampness, and have mild sweating. It is not only the wind-heat in exterior, but also can be combined with the pungent-cool exterior-releasing herbs to play the role of "window-opening heat dissipation". Radix Saposhnikoviae is a "humectant of wind-evil medicine", although herba Schizonepetae is warm and mild, the two herbs are compatible, and it also has the action of dispelling wind and relieving itching;

The Chinese angelica and the salvia miltiorrhiza are used as ministerial drugs in the formula for replenishing blood, removing blood stasis, relieving pain and cooling blood. Patients with blood stasis become weak after long-term illness, and the pruritus is aggravated by wind-movement due to blood deficiency, and angelica and salvia are ministerial in enriching and activating blood to help relieve itching;

the prescription takes belvedere fruit, dittany bark, lightyellow sophora root and Chinese tamarisk as adjuvant drugs. The broom cypress fruit, the cortex dictamni, the radix sophorae flavescentis and the cacumen tamaricis have the effects of clearing heat and drying dampness, dispelling wind and removing toxicity, and relieving itching as an assistant, and a monarch drug is assisted to assist in relieving itching;

the prescription uses tree peony bark, raw white peony root and red peony root as guide herbs. The moutan bark has the effects of clearing heat and cooling blood, the raw white paeony root and the red paeony root are used together, the raw white paeony root and the red paeony root are scattered and collected together, and the raw white paeony root and the red paeony root are discharged and supplemented together to play the roles of clearing heat and cooling blood, removing blood stasis and relieving itching and relieving pain.

Preferably, the pharmaceutical composition is prepared into paste, film and cataplasm by adding or omitting pharmaceutically acceptable auxiliary materials.

The method for preparing the pharmaceutical composition for treating the pruritus cutanea after hemodialysis comprises the following steps:

(1) mixing the Chinese medicinal materials, and pulverizing into fine powder;

(2) heating and liquefying solid vaseline in water bath, adding the fine powder obtained in the step (1), keeping, and then filtering and keeping filtrate;

(3) putting the filtrate in a water bath, adding glycerol, sodium thiosulfate and triamcinolone acetonide, and uniformly stirring to obtain the pharmaceutical composition.

As a preferable mode of the method of the present invention, the particle size of the fine powder in the step (1) is not less than 60 mesh.

As the optimization of the method, the addition amount of the solid vaseline is 2-3 mL/g of the traditional Chinese medicine raw materials.

As a preference of the process of the present invention, the retention time after the addition of the fine powder in step (2) is not less than 120 min.

Preferably, the volume ratio of the added amount of the glycerol to the vaseline is 1: 9-12; the dosage ratio of the sodium thiosulfate to the vaseline is 0.55-0.7 mol: 1L; the dosage ratio of triamcinolone acetonide to vaseline is 80-90 mg: 1L.

Preferably, the dosage ratio of the sodium thiosulfate to the vaseline is 0.6mol: 1L; the dosage ratio of triamcinolone acetonide to vaseline is 80mg: 1L.

In the end stage of hemodialysis and peritoneal dialysis of uremia patients, calcification defense often occurs, which is manifested by skin calcification and pruritus, and pain and ischemic skin necrosis are seen in the later stage. The sodium thiosulfate can inhibit vascular calcification by chelating calcium deposited in soft tissues, up-regulating calcification inhibitory factors and the like, and has the effects of relaxing capillary vessels and improving vascular endothelium so as to relieve calcification defense. Meanwhile, patients with chronic renal insufficiency are often accompanied by hypoadrenocortical function, and the secretion of adrenocortical hormone is absolutely insufficient, which affects the basic function of skin. Triamcinolone acetonide can be used for relieving pruritus caused by hypofunction of skin. The traditional Chinese medicine raw materials in the pharmaceutical composition are extracted from vaseline to obtain effective components, and then the effective components are compounded with glycerol, sodium thiosulfate and triamcinolone acetonide for use, so that the pharmaceutical composition has a remarkable effect of treating uremic pruritus cutanea.

The invention has the following beneficial effects:

the pharmaceutical composition can effectively treat and relieve pruritus cutanea appearing in uremia hemodialysis, has low cost and high applicability compared with hemoperfusion and hemodialysis combined treatment, and can be accepted by wide patients. Meanwhile, the pharmaceutical composition has quick response time for treating pruritus cutanea appearing in uremia hemodialysis, can have obvious treatment effect within two weeks, and relieves the pain of patients.

Drawings

Fig. 1(a, b, c) are photographs of the pruritus area before and after the treatment of patient I.

FIG. 2(a, b, c, d, e, f) is a photograph of the itching area before and after the treatment of patient II.

Fig. 3(a, b, c) are photographs of the itching area before and after treatment of patient III.

Fig. 4(a, b) are photographs of the itching area before and after the IV treatment of the patient.

Fig. 5(a, b, c) are photographs of the itching area before and after treatment of patient V.

Detailed Description

The following further describes the embodiments of the present invention.

The starting materials used in the present invention are commercially available or commonly used in the art, unless otherwise specified, and the methods in the following examples are conventional in the art, unless otherwise specified.

Example 1

A pharmaceutical composition for treating cutaneous pruritus after hemodialysis is prepared from the following traditional Chinese medicine raw materials in mass: 30g of schizonepeta, 30g of divaricate saposhnikovia root, 15g of Chinese angelica, 15g of salvia miltiorrhiza, 10g of tree peony bark, 30g of belvedere fruit, 30g of cortex dictamni, 15g of lightyellow sophora root, 15g of Chinese tamarisk, 15g of raw white paeony root and 15g of red paeony root.

The preparation process comprises the following steps:

(1) weighing the traditional Chinese medicine raw materials, mixing, crushing into fine powder, and sieving with a 100-mesh sieve;

(2) heating and liquefying solid medical white vaseline in 80 deg.C water bath to obtain 500mL liquid vaseline, adding the fine powder sieved in step (1), stirring, maintaining for 120min, filtering, and retaining the filtrate;

(3) and (3) putting the filtrate into a water bath at 80 ℃, sequentially adding 50mL of medical glycerol, 0.3mol of sodium thiosulfate and 40mg of triamcinolone acetonide, and uniformly stirring to obtain the pharmaceutical composition.

Example 2

A pharmaceutical composition for treating cutaneous pruritus after hemodialysis is prepared from the following traditional Chinese medicines in parts by mass: 24g of schizonepeta, 26g of divaricate saposhnikovia root, 13g of Chinese angelica, 12g of salvia miltiorrhiza, 8g of tree peony bark, 24g of belvedere fruit, 25g of cortex dictamni, 12g of lightyellow sophora root, 12g of cacumen tamaricis, 13g of raw white paeony root and 12g of red paeony root.

The preparation process comprises the following steps:

(1) weighing the traditional Chinese medicine raw materials, mixing, crushing into fine powder, and sieving with a 80-mesh sieve;

(2) Heating and liquefying solid medical white vaseline in 80 deg.C water bath to obtain 540mL liquid vaseline, adding the fine powder sieved in step (1), stirring, maintaining for 150min, filtering, and retaining the filtrate;

(3) putting the filtrate into a water bath at the temperature of 80 ℃, adding 60mL of glycerol, 0.30mol of sodium thiosulfate and 45mg of triamcinolone acetonide, and uniformly stirring to obtain the pharmaceutical composition.

Example 3

A pharmaceutical composition for treating cutaneous pruritus after hemodialysis is prepared from the following traditional Chinese medicines in parts by mass: 36g of herba schizonepetae, 35g of divaricate saposhnikovia root, 18g of Chinese angelica, 18g of salvia miltiorrhiza, 12g of moutan bark, 33g of fructus kochiae, 35g of cortex dictamni, 17g of radix sophorae flavescentis, 18g of cacumen tamaricis, 17g of raw white paeony root and 16g of red paeony root.

The preparation process comprises the following steps:

(1) weighing the traditional Chinese medicine raw materials, mixing, crushing into fine powder, and sieving with a 150-mesh sieve;

(2) heating and liquefying solid medical white vaseline in 80 deg.C water bath to obtain 510mL liquid vaseline, adding the fine powder sieved in step (1), stirring, maintaining for 150min, filtering, and retaining the filtrate;

(3) putting the filtrate into a water bath at 80 ℃, adding 43mL of glycerol, 0.35mol of sodium thiosulfate and 45mg of triamcinolone acetonide, and uniformly stirring to obtain the pharmaceutical composition.

1. Evaluation of Effect of application of the pharmaceutical composition of the present invention

1.1 clinical data: the total number of patients (the source of the cases is the seventh national hospital in overseas city), all included the following criteria:

(1) The skin itch symptom exists according with the uremia diagnosis standard;

(2) pruritus discomfort is more than or equal to 3 days/2 weeks and occurs frequently, which affects the life of patients;

(3) the pruritus lasts for more than 6 months;

(4) the age is more than or equal to 18 years old;

(5) clear recognition, no obvious obstruction, no serious diseases of blood system or immune system, etc.

And excluding those meeting any of the following conditions:

(1) patients with other skin diseases are combined;

(2) pregnant and lactating women;

(3) patients with drug allergy or patients who can not take the drug according to the requirement, and patients with incomplete follow-up data statistics;

(4) patients allergic to the traditional Chinese medicine;

(5) participate in new drug clinical trials not on the market in China, and cases that have not been revealed yet.

The patients who received the above were divided into a control group (26 cases) and a drug group (24 cases), and there was no statistical difference in the sex, age, dialysis time, physical condition and degree of skin itching between the two groups of cases.

1.2 methods of treatment

(1) Both groups maintained dialysis frequency of 3 times per week for 4 hours each, and received essentially the same normal diet;

(2) the control group adopts combined hemoperfusion treatment during hemodialysis;

(3) the drug group is coated with the ointment of the pharmaceutical composition prepared in example 1 at the itching site of the patient for 2 times a day for a fixed time (9: 00 am, 9:00 pm), and the dosage is just enough to uniformly cover the itching site, and the rest of the time is that the affected part with pruritus is uniformly coated;

(4) The treatment time is from 12 months in 2020 to 1 month in 2021 for two months, and the degree of improvement of symptoms at the itching site of the patients in the drug group is observed before the first dose every day, recorded, and scored according to the score table of SCORAD.

1.3 criteria for improvement of treatment were as follows:

and (3) curing: the scab of the skin fades away, the rash disappears and the pruritus does not appear any more; (score 0);

the effect is shown: the pruritus and the rash are obviously relieved; (score reduction > 50% before use);

the method has the following advantages: improvement of pruritus and rash symptoms; (score decrease < 50% before use);

and (4) invalidation: the itching and rash symptoms were not visibly changed. (no significant change in score).

The score for SCORAD (score of full 24) is tabulated as follows:

TABLE 1 SCORAD Scoring ____________/SCORAD (scanning Atomic Dermatitis index)

Scoring was performed both before and during treatment and at the time of time expiration.

1.4 statistics of the treatment effect of the two groups are shown in Table 2.

TABLE 2 two groups of statistical Effect

As can be seen from the above table, the pharmaceutical composition of the present invention has the following effects in treating uremia pruritus cutanea compared with the blood perfusion: the cure rate is lower than that of blood perfusion, but the curative ratio for treating the skin pruritus is kept effective, wherein the effective rate reaches 66.7 percent and is obviously higher than that of a control group. Two patients cured at the same time have no relapse before 2021, 5 months and 10 days, and the control group has 2 relapses.

2. Examples of the effects of the use of the pharmaceutical composition of the present invention in the above-mentioned drug groups

Patient I: shiji, male, age 58, met the criteria above, itching was on the back (as shown in FIG. 1a, 2020.12.7 shots), score 13 SCORAD before treatment, severe itching all over the body, scattered erythema, and scratch with dry skin. After the following treatment, the symptoms are obviously improved in two weeks, 9 scores of SCORAD show that the pruritus symptom is relieved, the erythema is removed, the scratch is reduced, and the skin is dry (as shown in figure 1b, 2020.12.21 is shot), and after the further treatment, the improvement is continued, 3 scores of SCORAD show that the skin is occasionally pruritus, no erythema and scratch exists, and the skin is slightly dry. (2020.12.25 shots as shown in FIG. 1 c), the result was significant.

Patient II: sunzhi, male, age 50, met the above criteria, had itching sites on both legs and legs (2020.12.5 shots as shown in FIG. 2 a) and on the back of the hand (2020.12.5 shots as shown in FIG. 2 b), score of SCORAD 21 points before treatment, severe itching and erythema on the rash sites, numerous scratches, subcutaneous edema and exudation on the ulcerated sites, and dry skin around the rash. After follow-up treatment, improvement occurred over 10 days (as shown in fig. 2c and 2d, 2020.12.15 shots), score 13 points for SCORAD, relief of pruritus symptoms, reduction of erythema area, reduction of scratch marks, scabbing at the ulcerated areas, pigmentation, reduction of edema, reduction of exudation, and significant relief at the dry skin areas before. After further treatment continued to improve (as shown in fig. 2e, 2f, 2020.12.21 shots), score 4 score for SCORAD, no obvious itching symptoms, no scratch marks, hyperpigmentation, dry skin, and significant effect was observed.

Patient III: xi Yi, an old woman, age 65, met the above criteria, the itching area was the scalp (as shown in fig. 3a, 2020.12.8), score 8 score for SCORAD before treatment, severe itching of the head skin, scattered rash, visible scratch, improvement after follow-up treatment in 20 days (as shown in fig. 3b, 2020.12.28 photograph), score 7 score for SCORAD, itching symptoms were relieved, rash was reduced, and a small amount of scratch was observed. After further treatment continued to improve (as shown in figure 3c, 2021.1.8 shots), score 1 score for SCORAD, occasional itching of the head skin, no rash and scratch, and significant results.

Patient IV: chen is a male, age 65, and meets the above criteria, the itching part is the chest and neck lower part (as shown in figure 4a, photographed by 2020.12.08), SCORAD score is 14 points before treatment, severe itching of the skin of the affected part is accompanied by erythema, pimple, loose scratch mark, dry skin around the body, healing appears after follow-up treatment for 8 days, SCORAD score is 0 point, no itching symptom is caused, erythema and pimple subside, pigmentation of the skin of the affected part (as shown in figure 4b, photographed by 2020.12.16) is resulted in healing.

Patient V: when a male is aged 56, the male meets the above standard, the itching part is the back (as shown in figure 5a, 2020.12.07 shooting), the score of SCORAD 21 points before treatment is followed, and after tracking treatment, the skin on the back is severely itchy, scattered in erythema and pimples, part of the skin is scabbed, a large number of scratches are formed, and the skin is dry. A reduction in skin dryness occurred over 8 days (as shown in figure 5b, 2020.12.15 shots), score 16 for SCORAD, relief of itching symptoms, earlier reduction in macula, fewer scratches, and earlier improvement in skin dryness. Further treatment continued to be reduced in minutes (2021.1.23 shots, as shown in figure 5 c), score of 11 SCORAD, mild itching of the skin, further reduction in macula, no obvious scratch, and efficacy.

Claims

1. The external pharmaceutical composition for treating the pruritus cutanea after hemodialysis is prepared from the following traditional Chinese medicine raw materials: 24-36 g of schizonepeta, 26-35 g of divaricate saposhnikovia root, 13-18 g of Chinese angelica, 12-18 g of salvia miltiorrhiza, 8-12 g of tree peony bark, 24-33 g of fructus kochiae, 25-35 g of cortex dictamni, 12-17 g of radix sophorae flavescentis, 12-18 g of cacumen tamaricis, 13-17 g of raw white paeony root and 12-16 g of red paeony root;

the method comprises the following steps:

(1) mixing the Chinese medicinal materials, and pulverizing into fine powder;

(3) putting the filtrate in a water bath, adding glycerol, sodium thiosulfate and triamcinolone acetonide, and uniformly stirring to obtain a pharmaceutical composition;

the adding amount of the solid vaseline is 2-3 mL/g of the traditional Chinese medicine raw material;

the dosage ratio of the sodium thiosulfate to the vaseline is 0.55-0.7 mol: 1L;

the dosage ratio of triamcinolone acetonide to vaseline is 80-90 mg: 1L.

2. The external pharmaceutical composition for treating cutaneous pruritus after hemodialysis according to claim 1, wherein the pharmaceutical composition comprises the following raw materials in parts by weight: 30g of schizonepeta, 30g of divaricate saposhnikovia root, 15g of Chinese angelica, 15g of salvia miltiorrhiza, 10g of tree peony bark, 30g of belvedere fruit, 30g of cortex dictamni, 15g of lightyellow sophora root, 15g of Chinese tamarisk, 15g of raw white paeony root and 15g of red paeony root.

3. The external pharmaceutical composition for treating cutaneous pruritus after hemodialysis according to claim 1, wherein the pharmaceutical composition is prepared into paste, membrane and paste by adding pharmaceutically acceptable auxiliary materials.

4. The external pharmaceutical composition for treating cutaneous pruritus after hemodialysis according to claim 1, wherein the particle size of the fine powder in the step (1) is not less than 60 meshes.

5. The topical pharmaceutical composition for treating pruritus cutanea after hemodialysis of claim 1, wherein the retention time after the addition of the fine powder in step (2) is not less than 120 min.

6. The external pharmaceutical composition for treating cutaneous pruritus after hemodialysis according to claim 1, wherein the volume ratio of the added amount of the glycerol to the vaseline is 1: 9-12.

7. The topical pharmaceutical composition for treating cutaneous pruritus after hemodialysis according to claim 1, wherein the amount ratio of sodium thiosulfate to vaseline is 0.6mol: 1L.

8. The topical pharmaceutical composition for treating cutaneous pruritus after hemodialysis according to claim 1, wherein the dosage ratio of triamcinolone acetonide to vaseline is 80mg: 1L.