Traditional Chinese medicine compound aerosol inhalant with kidney tonifying effect as well as preparation method and application of traditional Chinese medicine compound aerosol inhalant

Abstract

The invention discloses a traditional Chinese medicine compound aerosol inhalant with a kidney tonifying effect and a preparation method and application thereof.The aerosol inhalant is prepared from ginseng, lucid ganoderma, folium cortex eucommiae, raspberry, fructus lycii, longan aril, rhizoma polygonati, zaocys dhumnade and exocarpium citri rubrum, all the raw materials are matched and cooperated, the exocarpium citri rubrum is used for guiding meridians and guiding ingredients to be directionally distributed towards the kidney meridians, the kidney is tonifying without damaging other viscera, and the effect of tonifying the kidney is achieved. Through combination of raw material compatibility innovation, preparation process optimization and atomization administration, the defects of a traditional kidney-tonifying preparation are overcome, and the kidney-yang deficiency syndromes including soreness and weakness of waist and knees, intolerance of cold and cold limbs, frequent urination at night and other symptoms can be rapidly improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine preparation, in particular to a traditional Chinese medicine compound inhalation agent with kidney-tonifying effect and a preparation method and application thereof. BACKGROUND

[0002] Kidney deficiency syndrome is a common disease in traditional Chinese medicine, mainly manifested as symptoms such as soreness and weakness of waist and knees, aversion to cold and cold limbs, frequent nocturia, etc. Traditional kidney-tonifying Chinese medicine mainly adopts oral preparations (such as pills, decoctions, and capsules), which are easily affected by microorganisms and temperature, resulting in poor stability, and also have problems such as low bioavailability, slow effect, and influence of liver first-pass effect, etc. Therefore, it is of great significance to develop a kidney-tonifying Chinese medicine preparation with good stability and high bioavailability. SUMMARY

[0003] The core purpose of the present application is to provide a traditional Chinese medicine compound inhalation agent with kidney-tonifying effect, which has rapid effect, high bioavailability and good stability. The combination of "raw material compatibility innovation + preparation process optimization + atomization administration mode" solves the defects of traditional kidney-tonifying preparations.

[0004] To achieve the above-mentioned purpose, the present application provides the following technical scheme:

[0005] In a first aspect, the present application provides a traditional Chinese medicine compound inhalation agent with kidney-tonifying effect, which comprises the following raw material components in the following proportions: 10-20g of ginseng, 8-15g of ganoderma lucidum, 5-12g of eucommia leaf, 6-10g of raspberry, 8-15g of medlar, 5-10g of longan meat, 10-18g of polygonatum, 3-8g of rhabdophis, and 4-9g of orange red.

[0006] Further, the traditional Chinese medicine compound inhalation agent with kidney-tonifying effect has the following preferred proportions: 15g of ginseng, 12g of ganoderma lucidum, 8g of eucommia leaf, 8g of raspberry, 12g of medlar, 7g of longan meat, 15g of polygonatum, 5g of rhabdophis, and 6g of orange red.

[0007] Further, the traditional Chinese medicine compound inhalation agent with kidney-tonifying effect has the following pharmacological effects of each raw material:

[0008] Ginseng: The main active ingredients of ginseng, such as ginsenosides, polysaccharides, and volatile oils, can promote the secretion of adrenal cortical hormone and cortisol, rapidly improve the symptoms of kidney yang deficiency such as aversion to cold and cold limbs, and improve the immune function caused by kidney yang deficiency.

[0009] Reishi mushroom: It replenishes lung qi. Its active ingredients, such as polysaccharides, triterpenoids, and amino acids, enter the bloodstream, inhibit inflammatory factors, reduce renal interstitial fibrosis, promote the secretion of IL-2 and IFN-γ, enhance the phagocytic function of macrophages, reduce transaminase, improve renal function indicators, and relieve symptoms such as "lower back and knee pain, fatigue and weakness".

[0010] Eucommia ulmoides leaves: strengthen bones and muscles to tonify the kidneys. The active ingredient Eucommia ulmoides flavonoids can inhibit osteoclast activity, improve "lower back and knee pain and osteoporosis" caused by kidney yang deficiency, inhibit the activity of angiotensin-converting enzyme, reduce renal vascular resistance, increase renal blood flow, and improve renal tissue blood supply.

[0011] Raspberry: It benefits the kidneys and strengthens essence, reduces urination and stops nocturnal emission, nourishes the liver and kidneys, strengthens essence and improves eyesight. The active ingredients ellagic acid and anthocyanins reach the renal tubular epithelial cells, inhibit oxidative stress response, protect the renal tubules from damage, and improve the symptoms of kidney yang deficiency such as "frequent urination at night and clear urine".

[0012] Goji berries: Nourish the liver and kidneys, benefit essence and improve eyesight. The active ingredient, goji berry polysaccharide, promotes liver glycogen synthesis, improves symptoms of kidney yang deficiency such as dizziness, tinnitus and vision loss, enhances glutathione peroxidase activity, synergistically eliminates free radicals in kidney tissue, delays kidney aging, regulates blood sugar, and improves diabetic nephropathy.

[0013] Longan pulp: It nourishes the heart and spleen, replenishes blood and calms the mind. Its main active ingredients include polygonatum polysaccharides, steroidal saponins, flavonoids, etc., which can promote the synthesis of hemoglobin, replenish the "essence and blood of the same origin" material basis required for the kidney to store essence, and improve the symptoms of kidney yang deficiency such as "insomnia, dreaminess and palpitations".

[0014] Polygonatum: It replenishes qi and nourishes yin, strengthens the spleen, moistens the lungs and benefits the kidneys. Its active ingredient, Polygonatum steroidal saponin, can improve insulin resistance, reduce "high blood sugar and fatigue" associated with kidney yang deficiency, inhibit the proliferation of renal fibroblasts, reduce renal interstitial fibrosis, and protect kidney function.

[0015] Black-tailed snake: dispels wind and unblocks meridians, calms the nerves and stops spasms. Its active ingredient, snake venom polypeptide (such as nerve growth factor NGF), promotes the proliferation of glial cells, improves "numbness of limbs and contracture of waist and knees" caused by kidney yang deficiency, enhances the content of immunoglobulin IgG, synergistically improves the body's anti-rheumatism ability, and assists in tonifying the kidney.

[0016] Orange peel: It regulates qi, relieves chest congestion, dries dampness and resolves phlegm. Its main active ingredients include volatile oil (limonene) and flavonoids (hesperidin), which inhibit inflammation and promote absorption.

[0017] Secondly, the present invention provides a traditional Chinese medicine compound nebulized inhaler with kidney-tonifying effects, its preparation method and application, comprising the following steps:

[0018] (1) Raw material processing: Weigh each component of medicinal materials, mix them in proportion, pulverize them, and pass them through an 80-mesh sieve;

[0019] (2) Water extraction: Add 8-10 times the amount of double-distilled water, reflux at 85-90℃ twice, 1.5 hours each time;

[0020] (3) Membrane filtration: The extract was subjected to coarse filtration through a 5μm ceramic membrane and then ultrafiltration through a 3000Da ultrafiltration membrane at an operating pressure of 0.2-0.3MPa.

[0021] (4) Reverse osmosis concentration: The operating temperature is 35-40℃, and the membrane flux is controlled at 15-20L / (m²). 2 •h), using spiral wound membrane modules to concentrate to 1 / 5 of the original volume;

[0022] (5) Alcohol precipitation: Add 2.5 times the volume of 95% food-grade ethanol and let stand at 4°C for 12-14 hours;

[0023] (6) Centrifugation to remove impurities: Centrifuge at 4000 r / min for 20 minutes and collect the supernatant;

[0024] (7) Secondary concentration: Vacuum concentration until the ethanol content is <5% (v / v);

[0025] (8) Freeze-drying: After pre-freezing at -45℃, the compound freeze-dried powder is dried at 10Pa for 24 hours. The water content of the freeze-dried powder is ≤3% (w / w).

[0026] (9) Formulation preparation: Dissolve the compound freeze-dried powder in atomizing water to obtain a compound Chinese medicine aqueous solution, add food-grade propylene glycol or glycerol at a volume ratio of 1:0.8:0.2 and mix well to prepare a compound Chinese medicine nebulized inhaler.

[0027] Beneficial effects of the present invention

[0028] This invention, through a three-pronged design of "innovative raw material formulation + optimized preparation process + nebulized drug delivery," precisely addresses the problems of traditional kidney-tonifying preparations, such as "slow onset of action, low bioavailability, and poor stability." Its core beneficial effects include: synergistic compatibility of raw materials, targeted and safe delivery; tangerine peel acting as a guiding herb directing the components to the kidney meridian, achieving "tonifying the kidney without harming other organs"; and synergistic enhancement of efficacy through the combination of principal, assistant, and adjuvant herbs, rapidly relieving core symptoms of kidney yang deficiency such as aversion to cold, fatigue, and frequent urination. No decoction is required; nebulized drug delivery allows direct absorption through the respiratory tract, completely avoiding the first-pass effect of the gastrointestinal tract. Optimized processing improves the dissolution rate of active ingredients, solving the problem of "easily degradable components" in nebulized traditional Chinese medicine. It retains the advantages of "holistic conditioning" in traditional Chinese medicine while overcoming the defects of traditional preparations, providing a "highly effective, safe, and convenient" new treatment for kidney yang deficiency. Detailed Implementation

[0029] The present invention will be further described in detail below with reference to the embodiments. The embodiments are only intended to provide a clearer understanding of the technical features, objectives and effects of the present invention, and are not intended to limit the present invention.

[0030] Example 1

[0031] A traditional Chinese medicine compound nebulized inhaler with kidney-tonifying effects contains the following ingredients: 10g ginseng, 8g Ganoderma lucidum, 5g Eucommia ulmoides leaves, 6g raspberry, 8g wolfberry, 5g longan pulp, 10g Polygonatum sibiricum, 3g Zaocys dhumnades, and 4g Citrus reticulata peel.

[0032] A traditional Chinese medicine compound nebulized inhaler with kidney-tonifying effects, its preparation method, and its application are disclosed. The preparation steps are as follows: Weighed medicinal materials are mixed, pulverized, and passed through an 80-mesh sieve. Eight times the volume of double-distilled water is added, and the mixture is refluxed twice at 85-90℃ for 1.5 hours each time. Under an operating pressure of 0.2-0.3 MPa, the mixture is coarsely filtered through a 5μm ceramic membrane and treated with a 3000Da ultrafiltration membrane at an operating temperature of 35-40℃. The mixture is then concentrated to 1 / 5 of its original volume by reverse osmosis. 2.5 times the volume of 95% food-grade ethanol is added for alcohol precipitation. After standing at 4℃ for 12 hours, the supernatant is collected by centrifugation and concentrated again under vacuum until the ethanol content is <5% (v / v). After pre-freezing at -45℃, the mixture is dried at 10 Pa for 24 hours to obtain a compound lyophilized powder. The compound lyophilized powder is dissolved in nebulized water to obtain a traditional Chinese medicine compound aqueous solution. Food-grade propylene glycol or glycerol is added at a volume ratio of 1:0.8:0.2 and mixed well to prepare the traditional Chinese medicine compound nebulized inhaler.

[0033] Example 2

[0034] A traditional Chinese medicine compound nebulized inhaler with kidney-tonifying effects contains the following ingredients: ginseng 15g, Ganoderma lucidum 12g, Eucommia ulmoides leaf 8g, raspberry 8g, wolfberry 12g, longan pulp 7g, Polygonatum sibiricum 15g, Zaocys dhumnades 5g, and tangerine peel 6g.

[0035] The preparation method is described in Example 1.

[0036] Example 3

[0037] A traditional Chinese medicine compound nebulized inhaler with kidney-tonifying effects contains the following ingredients: ginseng 20g, Ganoderma lucidum 15g, Eucommia ulmoides leaf 12g, raspberry 10g, wolfberry 15g, longan pulp 10g, Polygonatum sibiricum 18g, Zaocys dhumnades 8g, and tangerine peel 9g.

[0038] The preparation method is described in Example 1.

[0039] Comparative Example 1 (lacking orange peel and raspberry)

[0040] A traditional Chinese medicine compound nebulized inhaler with kidney-tonifying effects contains the following ingredients: 15g ginseng, 12g Ganoderma lucidum, 8g Eucommia ulmoides leaves, 12g wolfberry, 7g longan pulp, 15g Polygonatum sibiricum, and 5g Zaocys dhumnades.

[0041] A traditional Chinese medicine compound nebulized inhaler with kidney-tonifying effects, its preparation method, and its application are disclosed. The preparation steps are as follows:

[0042] The weighed medicinal materials were mixed, pulverized, and passed through an 80-mesh sieve. Eight times the volume of double-distilled water was added, and the mixture was refluxed at room temperature for 1.5 hours for extraction. The mixture was then coarsely filtered through a 5μm ceramic membrane, treated with a 3000Da ultrafiltration membrane, and concentrated to 1 / 5 of its original volume by reverse osmosis at room temperature. Two times the volume of 95% food-grade ethanol was added for alcohol precipitation. After standing for 6 hours, the supernatant was collected by centrifugation and concentrated again under vacuum until the ethanol content was <5% (v / v). After pre-freezing at -45℃, the mixture was dried at 10Pa for 24 hours to obtain a compound lyophilized powder. The compound lyophilized powder was dissolved in nebulizer-specific water to obtain a traditional Chinese medicine compound aqueous solution. Food-grade propylene glycol or glycerol was added at a volume ratio of 1:0.8:0.2 and mixed well to prepare a traditional Chinese medicine compound nebulized inhalant.

[0043] Comparative Example 2 (lacking ginseng and eucommia leaves, and with insufficient quantities of other herbs)

[0044] A traditional Chinese medicine compound nebulized inhaler with kidney-tonifying effects contains the following ingredients: 3g Ganoderma lucidum, 9g raspberry, 10g wolfberry, 1g longan pulp, 5g Polygonatum sibiricum, 3g Zaocys dhumnades, and 6g tangerine peel.

[0045] The preparation method is described in Comparative Example 1.

[0046] Test

[0047] Subjects: Ten people aged 30-60 who felt cold in their hands and feet, frequently got up more than three times at night for urination, and felt tired and weak were recruited and divided into 5 groups of 2 people each.

[0048] Experimental Description: The following traditional Chinese medicine compound nebulizers were prepared using the formulation and preparation method of Example 1, Example 2, Example 3, Comparative Example 1, Comparative Example 2, and Comparative Example 3: Inhalation Nebulizer A1, Inhalation Nebulizer A2, Inhalation Nebulizer A2, Inhalation Nebulizer B1, and Inhalation Nebulizer B2. The five groups of inhalation nebulizers were: Group 1: Inhalation Nebulizer A1, Group 2: Inhalation Nebulizer A2, Group 3: Inhalation Nebulizer A3, Group 4: Inhalation Nebulizer B1, and Group 5: Inhalation Nebulizer B2.

[0049] Nebulization method: Nebulize twice a day, and continuously monitor the improvement of symptoms for 1 month.

[0050] Group 1, consisting of 2 people, inhaled the nebulizer A1 from Example 1:

[0051] On the 7th day after inhaling the nebulizer, fatigue was reduced, and it was not easy to feel weak after daily activities. On the 12th day, the fear of cold was eliminated, the frequency of urination at night decreased, and there were no dark circles under the eyes. On the 21st day, there was no need to get up at night to urinate. The patient felt energetic in the morning, and there was no obvious drowsiness or sleepiness in the afternoon. The symptoms of lower back and knee pain were relieved, and the cold pain was reduced. The flexibility of bending over and squatting was improved, and there was no "worsening of lower back pain after sitting or standing for a long time".

[0052] Group 2 (2 people) inhaled the nebulizer A2 of Example 2:

[0053] On the 6th day after inhaling the nebulizer, fatigue was reduced, and it was not easy to feel weak after daily activities. On the 12th day, the fear of cold was eliminated, the frequency of urination at night decreased, and there were no dark circles under the eyes. On the 19th day, there was no need to get up at night to urinate. The patient felt energetic in the morning, and there was no obvious drowsiness or sleepiness in the afternoon. The symptoms of soreness and cold pain in the lower back and knees were relieved, and the flexibility of bending over and squatting was improved. There was no "worsening of lower back pain after sitting or standing for a long time".

[0054] Group 3, consisting of 2 people, inhaled the nebulizer A3 from Example 3:

[0055] On the 6th day after inhaling the nebulizer, fatigue was reduced, and it was not easy to feel weak after daily activities. On the 10th day, the fear of cold was eliminated, the frequency of urination at night decreased, and there were no dark circles under the eyes. On the 15th day, there was no need to get up at night to urinate. The patient felt energetic in the morning, and there was no obvious drowsiness or sleepiness in the afternoon. The symptoms of lower back and knee pain were relieved, and the cold pain was reduced. The flexibility of bending over and squatting was improved, and there was no "worsening of lower back pain after sitting or standing for a long time".

[0056] Group 4, consisting of 2 individuals, inhaled nebulizer B1 from Comparative Example 1:

[0057] On the 8th day after inhaling the nebulizer, fatigue was reduced and it was not easy to feel weak after daily activities. On the 15th day, the feeling of cold and aversion to cold was relieved. On the 30th day, fatigue was relieved, but symptoms such as lower back and knee pain, frequent urination and urgency were not relieved.

[0058] Group 5 (2 people) inhaled nebulizer B2 from Comparative Example 2:

[0059] On the 10th day after inhaling the nebulizer, the frequency of urination at night decreased. On the 30th day, the fatigue was relieved, but the symptoms such as lower back and knee pain, frequent urination and urgency did not improve further.

[0060] Based on the above experimental tests, it is clear that the nebulizer, made strictly according to the formula and preparation method, can quickly relieve the core symptoms of kidney yang deficiency such as aversion to cold, fatigue, and frequent urination.

[0061] The embodiments of the present invention are merely specific descriptions of the technical solutions and are not intended to limit the technical solutions. Any substitutions or modifications made by those skilled in the art without changing the essential content of the present invention shall fall within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine compound nebulized inhaler with kidney-tonifying effects, characterized in that, It is composed of the following ingredients by weight: ginseng 10-20g, Ganoderma lucidum 8-15g, Eucommia ulmoides leaves 5-12g, raspberry 6-10g, wolfberry 8-15g, longan pulp 5-10g, Polygonatum sibiricum 10-18g, Zaocys dhumnades 3-8g, and tangerine peel 4-9g.

2. The traditional Chinese medicine compound nebulized inhaler according to claim 1, characterized in that, The preferred ratio is: Ginseng 15g, Ganoderma lucidum 12g, Eucommia ulmoides leaf 8g, raspberry 8g, wolfberry 12g, longan pulp 7g, Polygonatum sibiricum 15g, Zaocys dhumnades 5g, tangerine peel 6g.

3. The traditional Chinese medicine compound nebulized inhaler according to claim 1 or 2, characterized in that, The preparation method includes the following steps: (1) Raw material processing: Weigh each component of medicinal materials, mix them according to the proportion, pulverize them, and pass them through an 80-mesh sieve; (2) Water extraction: Add 8-10 times the amount of double-distilled water, reflux at 85-90℃ twice, 1.5 hours each time; (3) Membrane filtration: The extract was sequentially subjected to coarse filtration through a 5μm membrane and ultrafiltration through a 3000Da membrane; (4) Reverse osmosis concentration: Concentrate to 1 / 5 of the original volume using spiral wound membrane modules; (5) Alcohol precipitation: Add 2.5 times the volume of 95% food-grade ethanol and let stand at 4°C for 12-14 hours; (6) Centrifugation to remove impurities: Centrifuge at 4000 r / min for 20 minutes and collect the supernatant; (7) Secondary concentration: Vacuum concentration until the ethanol content is <5% (v / v); (8) Freeze-drying: After pre-freezing at -45℃, the compound freeze-dried powder was obtained by drying at 10Pa for 24 hours; (9) Formulation preparation: Dissolve the compound freeze-dried powder in atomizing water to obtain a compound Chinese medicine aqueous solution, add food-grade propylene glycol or glycerol at a volume ratio of 1:0.8:0.2 and mix well to prepare a compound Chinese medicine nebulized inhaler.

4. The preparation method according to claim 3, characterized in that... In step (3), a ceramic membrane is used for coarse filtration, and the operating pressure is 0.2-0.3 MPa.

5. The preparation method according to claim 3, characterized in that... Step (4) The operating temperature for reverse osmosis concentration is 35-40℃, and the membrane flux is controlled at 15-20L / (m²). 2 ·h).

6. The preparation method according to claim 3, characterized in that... In step (8), the water content of the lyophilized powder is ≤3% (w / w), and the conductivity of the solution is controlled to be <50μS / cm during reconstitution.

7. The preparation method according to claim 3, characterized in that... After preparation in step (9), the solution is filtered through a 0.22μm microporous membrane terminal.

8. The application of the traditional Chinese medicine compound nebulized inhaler according to claim 1 or 2 in the preparation of kidney-tonifying drugs, characterized in that... Administered via nebulized inhalation, 1-2 times daily, with each nebulization dose being 3-5 mL.

9. The application according to claim 8, characterized in that... The drug is used to improve symptoms of kidney yang deficiency, including soreness and weakness of the lower back and knees, aversion to cold and cold limbs, and frequent urination at night.