Mongolian butter intestine moistening and bowel relaxing patch and preparation process thereof

Abstract

The invention relates to the technical field of medicine, and particularly discloses a Mongolian butter intestine moistening and bowel relaxing patch and a preparation technology thereof.The patch is prepared from, by weight, 10-20 parts of rheum officinale and myrobalan extracts, 5-10 parts of dietary alkali, 2-5 parts of Mongolian butter, 1-3 parts of sodium polyacrylate NP-700, 4-6 parts of glycerinum, 1-3 parts of a transdermal enhancer and 50-80 parts of 50% ethyl alcohol. The Mongolian butter plaster is compatible with multiple medicinal materials, all the medicinal materials have a synergistic effect, the effects of moistening dryness, lubricating intestines, enhancing transportation and transformation capabilities of the spleen and the stomach, increasing absorption of influencing substances and improving vigor and immunity of a human body are achieved, and the Mongolian butter plaster is prepared from edible butter, dietary alkali and natural plant extracts, is safe and free of irritation and is suitable for being used by the human body for a long time. The traditional Chinese medicine composition avoids liver first-pass effect drug stimulation caused by oral administration, is noninvasive in administration, improves the compliance of patients, is convenient to use, can be independently taken by the patients, and is particularly suitable for infants, old people, patients not suitable for oral administration and the like.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines, and in particular relates to a Mongolian butter laxative patch and a preparation process thereof. Background Art

[0002] Butter, called "Xi Ri Tao Su" in Mongolian, is made from milk and is produced by naturally grazing yellow cattle. It has a unique and pure taste. It is not only rich in nutrients, but also has multiple functions and effects. Research reports show that: ① Mongolian butter is rich in linoleic acid, an important -6 polyunsaturated fatty acid. Linoleic acid has anti-inflammatory effects and can help regulate blood lipids and blood sugar levels to prevent cardiovascular diseases and diabetes. ② The fat in Mongolian butter helps lubricate the gastrointestinal tract and promote food digestion and absorption. At the same time, the milky white cinnamic acid lipids in butter also have a bactericidal effect, which is beneficial to the health of the digestive system. ③ Nutrients such as vitamins A, D and E in Mongolian butter can enhance the function of the human immune system, improve resistance, and prevent infection and disease. Vitamins A and E in Mongolian butter help maintain the health and smoothness of the skin. It can be used as a moisturizer to help repair the skin and relieve problems such as dryness and itching. ④ In particular, Mongolian butter has unique physical properties. It is a light yellow solid at room temperature and has a unique frankincense aroma after being heated and melted. The melting point of butter is 35 degrees Celsius. After the butter-blended medicine is applied, it melts at body temperature and is easy for the active ingredients of the medicine to be absorbed through the skin. However, there are no research reports on related compound products at home and abroad.

[0003] Mongolian medicine Gexi Guna-3 Decoction is also known as Zhumuza-3 Decoction and Dahuang Sanwei Decoction. This recipe originated from the classic work "Four Medical Classics" and was included in the "Inner Mongolia Mongolian Patent Medicine Standards" in 1984. It is a decoction made of three herbs: rhubarb, terminalia chebula, and alkaline noodles. It is a classic Mongolian medicine preparation commonly used in clinical practice to treat descending Heyi dysfunction, abdominal distension, constipation, and amenorrhea. At present, it is clinically used for the prevention and treatment of postoperative gastrointestinal dysfunction during the perioperative period, and has achieved good results. However, traditional Mongolian medicine decoctions have the disadvantages of bitter taste, large quantity, inconvenient decoction, and difficulty in storage and carrying. At the same time, it not only affects the patient's compliance, but also cannot be used for patients who are not suitable for oral administration. Summary of the invention

[0004] The purpose of the present invention is to provide a Mongolian butter laxative patch and a preparation process thereof, so as to solve the problems raised in the above-mentioned background technology.

[0005] To achieve the above object, the present invention provides the following technical solutions:

[0006] A Mongolian butter laxative patch:

[0007] The invention comprises the following raw materials in parts by weight: 10-20 parts of rhubarb and terminalia chebula extracts, 5-10 parts of edible alkali, 2-5 parts of Mongolian butter, 1-3 parts of sodium polyacrylate NP-700, 4-6 parts of glycerol, 1-3 parts of transdermal enhancer, and 50-80 parts of 50% ethanol.

[0008] A preparation process of Mongolian butter laxative patch comprises the following steps:

[0009] S1. Select high-quality raw materials of rhubarb and terminalia chebula, remove impurities and moldy raw materials, and crush the raw materials of rhubarb and terminalia chebula through a 30-mesh sieve;

[0010] Place the sieved powder in a round-bottom flask and add 50% ethanol. The amount of ethanol should be enough to cover the medicinal material by 2-3 cm.

[0011] Extract with 50% ethanol by heating and refluxing for 3 times, 2 hours each time, filter, combine the filtrate, evaporate and recover the ethanol by rotary evaporator, concentrate in vacuum rotary concentrator to a clear paste with relative density of 1.15-1.25g / ml, seal and store for later use;

[0012] S2. Take out 30g of clear paste and add 10g of edible alkali, use a stirring device, stir continuously at a speed of 300-500r / min for 1-2 minutes, stir to dissolve, and set aside;

[0013] S3. Mix Mongolian butter and 10g glycerol in a mass ratio of 1:2, heat at 40-50°C and mix well, add 1g sodium polyacrylate NP-700 and stir while heating, then add the prepared drug ointment and 1ml of skin penetrant azone in sequence, continue stirring for 30-45 minutes to form a drug-containing gel solution;

[0014] S4. Evenly apply the drug-containing glue solution on the anti-adhesive layer with a coating thickness of 1-2 mm, and then place it to dry at room temperature for 48 hours. After cross-linking and curing, cover it with the backing layer to obtain the Mongolian butter patch.

[0015] Compared with the prior art, the present invention has the following beneficial effects:

[0016] The Mongolian butter plaster of the present invention is compatible with multiple medicinal materials. The main drug is rhubarb, which has excellent dilution, softness and laxative effect; it is matched with terminalia chebula to play the role of detoxification and regulating the essence, and then assisted by alkaline noodles for digestion and laxative, to synergistically assist intestinal transportation and transformation. Assisted by Mongolian butter, it has multiple functions such as moisturizing and lubricating the intestines, strengthening the stomach and body, adding heat, prolonging life, and nourishing the skin. It not only fully assists the main drug to achieve the goal of moisturizing the intestines and relieving constipation, but also promotes the smooth discharge of toxins from the body, and allows the various drugs to form a close force, further improve the spleen and stomach transportation and transformation ability, and optimize the absorption efficiency of nutrients. And edible butter, edible alkali and natural plant extracts are used, the ingredients are natural and mild, safe and non-irritating, and suitable for long-term use by the human body.

[0017] The present application avoids the first-pass liver effect drug irritation to the gastrointestinal tract that occurs during oral administration, and the administration is non-invasive, improves patient compliance, is easy to use, and patients can take the medicine independently and interrupt the administration at any time. It can also be used for unresponsive, unconscious comatose patients, and is especially suitable for infants, the elderly, and patients who are not suitable for oral administration, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 A schematic diagram of the process of the present invention;

[0019] Figure 2 Schematic diagram of the feces texture in the experimental series of the present invention compared with the control group;

[0020] Figure 3 This is a mapping diagram of the metabolite database of the Mongolian butter patch of the present invention. DETAILED DESCRIPTION

[0021] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0022] Embodiment 1:

[0023] A Mongolian butter laxative patch,

[0024] The invention comprises the following raw materials in parts by weight: 15 parts of rhubarb and terminalia chebula extracts, 8 parts of edible alkali, 3 parts of Mongolian butter, 2 parts of sodium polyacrylate NP-700, 5 parts of glycerol, 2 parts of a transdermal enhancer (azone is selected) and 65 parts of 50% ethanol.

[0025] Preparation process:

[0026] S1. Extraction of medicinal materials to make clear paste:

[0027] Carefully select high-quality raw rhubarb and terminalia chebula, carefully remove impurities and moldy parts, use a universal grinder to grind the raw rhubarb and terminalia chebula, and pass through a 30-mesh sieve.

[0028] Transfer the sieved powder to a round-bottom flask of appropriate size, slowly add 50% ethanol, so that the ethanol liquid level is about 2.5 cm above the medicinal material. Connect the heating reflux device, turn on the heating, adjust the temperature to a suitable state, keep the ethanol at a slight boiling point, and perform heating reflux extraction three times, each time precisely controlled to 2 hours.

[0029] After the extraction is completed, filter with filter paper while it is hot and collect the filtrate into a clean container; repeat the filtration operation twice and combine the three filtrates. Place the combined filtrate in a rotary evaporator, set the parameters, and recover the ethanol; then transfer the remaining liquid to a vacuum rotary concentrator and concentrate it under vacuum. Continuously monitor the relative density until it is concentrated to a clear paste with a relative density of 1.20g / ml, and seal it and store it in a cool, dry place for later use.

[0030] S2. Mix the clear paste with edible alkali:

[0031] Accurately weigh 30 g of the prepared paste, place it in a clean stainless steel stirring container, and then add 10 g of edible alkali.

[0032] Turn on the stirring equipment, adjust the speed to 400r / min, and continue stirring for 1.5 minutes until the edible alkali is completely dissolved in the clear paste to obtain a uniform mixed liquid for use.

[0033] S3. Mixing the matrix and the drug to prepare the drug-containing gel solution:

[0034] According to the mass ratio of 1:2, weigh 3 parts of Mongolian butter and 10g of glycerin, put them into a container with heating and stirring functions, and gradually heat them to 45°C. During the heating process, start the stirring paddle and stir at a speed of 300r / min to mix the two evenly.

[0035] After the Mongolian butter and glycerin are evenly mixed, add 2 parts of sodium polyacrylate NP-700 into the system, maintain the stirring speed, and continue stirring for 18 minutes.

[0036] Then slowly add the prepared drug ointment. After the addition is completed, add 2 parts (1 ml) of azone as a skin penetrant, and continue stirring for 35 minutes to finally form a drug-containing gel with a uniform texture.

[0037] S4. Patch molding:

[0038] Spread the anti-sticking layer material evenly on the workbench of the coating machine, adjust the coating head, evenly apply the drug-containing glue liquid on the anti-sticking layer, and strictly control the coating thickness to 1.5 mm.

[0039] After coating, place the anti-sticking layer with the drug-containing glue in a well-ventilated and room temperature stable environment, let it dry for 48 hours, and wait for the glue to completely cross-link and cure.

[0040] Finally, select a suitable backing layer material, carefully cover it on the solidified medicine patch layer, and use a pressing device to gently press it to ensure a tight fit without bubbles or wrinkles, and the Mongolian butter patch is successfully produced.

[0041] Experimental Example 1:

[0042] The efficacy of Mongolian butter patch in treating constipation confirmed by the measurement of fecal water content

[0043] Experimental method: Figure 1 As shown,

[0044] Forty SD rats, half male and half female, were selected and acclimatized under constant temperature and humidity conditions for 7 days.

[0045] The rats were randomly divided into normal control group (A), model group (B), experimental group (C), positive control group (D), and original drug group (E).

[0046] Except for the normal control group, the other groups of animals were gavaged with "loperamide hydrochloride capsules" to establish chronic constipation models; after successful modeling, the rats in the normal control group and the model group were gavaged with equal volumes of normal saline, and the rats in the positive control group were given commercially available Biantong capsules at a rate of 1.2 g / 200 g per gavage, once a day; the rats in the original drug group were given Mongolian medicine Gexiguna-3 soup at a rate of 1.04 g / kg per gavage, once a day; the experimental group applied the prepared Mongolian butter patch on the abdomen of the rats for 12 hours each time, and the drug was administered for 3 consecutive days; the feces characteristics, texture, and feces water content of the rats were observed, and statistical SPS19.0 analysis was performed to investigate the intestinal moisturizing and laxative efficacy of the Mongolian butter patch.

[0047] Fecal moisture content: A certain amount of fresh feces was collected before modeling, after modeling and after drug administration, weighed and placed in a 60°C oven for drying until the feces weight no longer changed. The dry weight of the feces was then weighed to calculate the fecal moisture content of the rats. The calculation formula is as follows: Fecal moisture content (%) = (wet weight - dry weight) / dry weight × 100%.

[0048] 1. Comparison of fecal properties, texture and water content among rats in each group

[0049] (1) The feces of rats in each group after drug administration were compared. Compared with the control group, the feces of the model group were smaller in particles and harder in texture. When the rats were killed and dissected, it was also found that the feces remaining in the colon of the model group were harder and drier than those in the control group. The feces of the Mongolian butter patch group and the original drug Gexigun-3 decoction group were close to that of the normal control group. Figure 1 .

[0050] A. Normal control group B. Model group C. Mongolian butter patch group D. Positive control group E. Original drug Gexiguna-3 decoction group

[0051] (2) The fecal water content of rats in each group was compared before and after the experiment. Compared with the blank control group, the fecal water content of rats in each modeling group was significantly reduced after modeling (P < 0.01); compared with the model group, the fecal water content of rats in the plaster group was significantly increased (P < 0.05), and there was no statistically significant difference between the plaster group and the positive control group (P > 0.05). The results showed that Mongolian butter patch can effectively increase the fecal water content of rats and improve the constipation of rats.

[0052] The results are shown in Table 1.

[0053] Table 1 Water content of feces of rats in each group before and after the experiment (n=8, )

[0054]

[0055] Note: *Compared with the blank group, P<0.01; ▲Compared with the model group, P<0.01.

[0056] Conclusion: The Mongolian Butter Patch has significant efficacy and has no significant difference from the original drug Gexigun-3 Decoction.

[0057] Experimental Example 2:

[0058] The following is the comparative data between the Mongolian Butter Transdermal Patch treatment group and the existing control group in this application:

[0059] General information of patients in the two groups

[0060] Forty patients with advanced colorectal cancer who were hospitalized in the Affiliated Hospital of Inner Mongolia University for Nationalities from June 2019 to November 2024 were selected as the research subjects. The diagnostic criteria were based on the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) eighth edition of the colorectal cancer TNM staging system in the "Chinese Colorectal Cancer Diagnosis and Treatment Guidelines 2017 Edition" to select patients with stage II and III. All patients underwent laparoscopic radical resection of colorectal cancer under general anesthesia and were randomly divided into a control group of 20 cases and a treatment group of 30 cases according to the order of hospitalization. There were 16 males and 14 females in the control group; the average age was 65.37±12.79 years old, and the average operation time was 201.3±68.65 (S); there were 13 males and 17 females in the treatment group; the average age was 67.53±10.11 years old, and the average operation time was 190.57±50.97 (S). There was no significant difference in gender, age, operation time, etc. between the two groups of patients (P>0.05).

[0061] Efficacy evaluation

[0062] Comparison of postoperative bowel sound recovery time, first anal flatus time and first anal defecation time between the two groups of patients

[0063] The time for bowel sound recovery in the Mongolian Butter Patch treatment group was significantly shorter than that in the blank control group, and statistical analysis showed that the difference was significant (p < 0.05); the effect of Mongolian Butter Patch on the time of first anal flatus after radical resection of colorectal cancer, the anal flatus time in the Mongolian Butter Patch group was compared with the blank control group, and statistical analysis showed that the difference was significant (p < 0.01); the time for first anal defecation in the Mongolian Butter Transdermal Patch treatment group was significantly shorter than that in the blank control group, and statistical analysis showed that the difference was significant (p < 0.05).

[0064] Table 2 Comparison of postoperative bowel sound recovery time, first anal flatus time and first anal defecation time between the two groups of patients (h, )

[0065]

[0066]

[0067] Note: t test between groups, intestinal motility recovery time after treatment between groups *P<0.05, ▲P<0.01.

[0068] Effect of Guyouyou Plaster on the levels of vasoactive intestinal peptide and procalcitonin in patients after radical surgery for colorectal cancer:

[0069] There was no significant difference in the vasoactive intestinal peptide content before treatment in the Mongolian butter patch treatment group compared with the blank control group. There was a significant difference in the vasoactive intestinal peptide content before and after treatment in the Mongolian butter patch treatment group compared with that before treatment (P < 0.01). There was a significant difference in the vasoactive intestinal peptide content after treatment in the Mongolian butter patch treatment group compared with the blank control group (P < 0.05). The results are shown in Table 3.

[0070] Table 3 Comparison of postoperative vasoactive intestinal peptide (VIP) and procalcitonin levels between the two groups of patients

[0071]

[0072] Note: The data of the two groups were tested by t-test, comparison of vasoactive intestinal peptide content before and after treatment with Mongolian butter patch (*P<0.01); t-test between groups, comparison between Mongolian butter patch treatment and blank control group (▲P<0.05); comparison of vasoactive intestinal peptide and procalcitonin content between groups before treatment (p>0.05); comparison between groups after treatment (*p<0.01) and comparison of Mongolian butter transdermal patch treatment group before and after treatment (*p<0.01).

[0073] Experimental Example 3 Analysis of blood components of Mongolian Butter Patch

[0074] Three healthy subjects who voluntarily signed the informed consent form were selected and Mongolian butter plaster (3×3 cm) was applied to Shenjue and Qihai points, with the patch changed every 12 hours for 24 hours. 5 mL of venous blood was collected and centrifuged to obtain serum. Metabolomics analysis based on LC-MS showed that among the 7 substances before entering the blood, the effective components of butter (linseed oleic acid, 11,14-eicosadienoic acid, and linoleic acid) were significantly higher than those of the 7 substances before entering the blood. Figure 2 .

[0075] This result shows that Mongolian butter has good transdermal properties and the effective ingredients enter the blood quickly. Adding Mongolian butter in this application can greatly increase the transdermal effect of the drug, improve the bioavailability of the drug, and enhance the efficacy. In addition, adding edible alkali and rhubarb and terminalia chebula extracts in this application can play a role in excipients for the plaster.

[0076] in Figure 2 This is a mapping diagram of the metabolite database of the Mongolian butter patch of the present invention.

[0077] It will be appreciated that in the development of any actual implementation, as in any engineering or design project, numerous implementation-specific decisions may be made. Such a development effort may be complex and time-consuming, but will be a routine task of design, fabrication, and production for those of ordinary skill having the benefit of this disclosure without undue experimentation.

[0078] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the claims of the present invention.

Claims

1. A Mongolian butter laxative patch, characterized in that: The invention comprises the following raw materials in parts by weight: 10-20 parts of rhubarb and terminalia chebula extracts, 5-10 parts of edible alkali, 2-5 parts of Mongolian butter, 1-3 parts of sodium polyacrylate NP-700, 4-6 parts of glycerol, 1-3 parts of a transdermal enhancer and 50-80 parts of 50% ethanol.

2. The preparation process of a Mongolian butter laxative patch according to claim 1, characterized in that: The following steps are involved: S1. Select high-quality raw materials of rhubarb and terminalia chebula, remove impurities and moldy raw materials, and crush the raw materials of rhubarb and terminalia chebula through a 30-mesh sieve; Place the sieved powder in a round-bottom flask and add 50% ethanol. The amount of ethanol should be enough to cover the medicinal material by 2-3 cm. Extract with 50% ethanol by heating and refluxing for 3 times, 2 hours each time, filter, combine the filtrate, evaporate and recover the ethanol by rotary evaporator, concentrate in vacuum rotary concentrator to a clear paste with relative density of 1.15-1.25g / ml, seal and store for later use; S2. Take out 30g of clear paste and add 10g of edible alkali, use a stirring device, stir continuously at a speed of 300-500r / min for 1-2 minutes, stir to dissolve, and set aside; S3. Mix Mongolian butter and 10g glycerol in a mass ratio of 1:2, heat at 40-50°C and mix well, add 1g sodium polyacrylate NP-700 and stir while heating, then add the prepared drug ointment and 1ml of skin penetrant azone in sequence, continue stirring for 30-45 minutes to form a drug-containing gel solution; S4. Evenly apply the drug-containing glue solution on the anti-adhesive layer with a coating thickness of 1-2 mm, and then place it to dry at room temperature for 48 hours. After cross-linking and curing, cover it with the backing layer to obtain the Mongolian butter patch.

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