Traditional Chinese medicine composition for the treatment of pelvic inflammatory disease, its thermosensitive gel and drug delivery device

Abstract

This invention discloses a traditional Chinese medicine composition for the treatment of pelvic inflammatory disease, along with its thermosensitive gel and drug delivery device, belonging to the fields of traditional Chinese medicine and medical device technology. The traditional Chinese medicine composition is composed of Sichuan pepper, vinegar-processed corydalis, luffa cylindrica, cinnamon twig, angelica sinensis, red peony root, poria cocos, and earthworm in a specific ratio, with the core treatment principle of soothing the liver and regulating qi, promoting blood circulation and unblocking collaterals, targeting the syndrome of qi stagnation and blood stasis, and obstructed meridians. This composition can be formulated into a thermosensitive vaginal gel, using poloxamer as a matrix, exhibiting room temperature flow and body temperature solidification characteristics, which can prolong the local drug retention time. The accompanying drug delivery device has four interchangeable delivery heads: a single-point delivery head (No. 1) for deep targeted therapy, an umbrella-shaped delivery head for easy drug emptying, an array delivery head for uniform coverage of the vaginal wall, and a directional delivery head that can be adjusted at an angle to act on lesions on the lateral wall. This invention provides a more efficient and personalized solution for the treatment of chronic pelvic inflammatory disease.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine and medical device technology, specifically a traditional Chinese medicine composition for the treatment of pelvic inflammatory disease, its thermosensitive gel, and its drug delivery device. Background Technology

[0002] Pelvic inflammatory disease (PID) is a group of infectious diseases caused by pathogens infecting the female upper reproductive tract and surrounding tissues.

[0003] Traditional Chinese medicine (TCM) categorizes chronic pelvic inflammatory disease (PID) under the categories of "abdominal pain in women," "abdominal masses," and "leukorrhea." Currently, most clinically used and marketed TCM preparations follow the basic treatment principles of "clearing heat and promoting diuresis" or "tonifying qi and removing blood stasis." For example, formulas combining heat-clearing and detoxifying herbs (such as honeysuckle and dandelion) with blood-activating herbs (such as danshen and red peony) primarily target the "damp-heat stagnation" syndrome; while the approach of combining qi-tonifying herbs (such as astragalus) with blood-activating and stasis-removing herbs focuses on the "qi deficiency and blood stasis" syndrome. These approaches have achieved definite efficacy within their respective indications and constitute the current mainstream treatment. However, clinical observations have revealed that a considerable number of patients present with lower abdominal distending or stabbing pain, fixed in location or migratory, significantly aggravated by emotional fluctuations and before and after menstruation, often accompanied by poor menstrual flow, breast distension, a dark tongue or petechiae, and a wiry or hesitant pulse. The core pathogenesis of this syndrome lies in "stagnation of Qi, poor blood circulation, and obstruction of the meridians," that is, "Qi stagnation and blood stasis, and blocked meridians." Current mainstream Chinese medicine formulas are relatively weak in their medicinal properties for "soothing the liver and regulating Qi, clearing the meridians and relieving pain," resulting in insufficient targeted treatment for this specific syndrome type, and room for improvement in efficacy.

[0004] On the other hand, vaginal local administration is an important route of treatment for pelvic inflammatory disease, its value lying in its ability to directly target the lesion area and increase local drug concentration. However, existing vaginal dosage forms, such as suppositories and conventional gels, generally have inherent defects. After administration, it is difficult to precisely control the distribution of the drug, which often diffuses widely within the vagina, failing to effectively target deep critical lesions such as the cervical canal and fallopian tube openings, or localized inflammatory areas on the vaginal wall. Simultaneously, these dosage forms have a short retention time in the body, especially gels, which are easily lost due to changes in body position or flushing by bodily fluids, failing to achieve long-term sustained release of the drug, thus affecting treatment efficacy and increasing dosing frequency. A deeper problem is that the development of existing drug formulations and drug delivery devices is often separate. The market lacks dedicated formulations that can be deeply synergistically designed with advanced drug delivery devices that possess multi-modal and adjustable functions. This disconnect between "drug" and "device" makes it difficult to achieve personalized and precise clinical drug delivery even with more targeted drugs, failing to maximize the therapeutic potential of the drugs. Summary of the Invention

[0005] The purpose of this invention is to provide a traditional Chinese medicine composition for the treatment of pelvic inflammatory disease, as well as its thermosensitive gel and drug delivery device. The composition takes "soothing the liver and regulating qi, promoting blood circulation and unblocking collaterals, warming the meridians and relieving pain" as its core treatment principle. Its thermosensitive gel dosage form can undergo a phase change at body temperature, prolonging the residence time of the drug at the site of action and achieving sustained release. At the same time, the drug delivery device enables precise and long-term delivery of the drug to deep, diffuse or localized lesions.

[0006] To achieve the above objectives, the present invention provides the following technical solution: In a first aspect, the present invention provides a traditional Chinese medicine composition for the treatment of pelvic inflammatory disease, made from the following raw materials in parts by weight: 5-15 parts of Sichuan pepper, 10-20 parts of vinegar-processed corydalis rhizome, 10-20 parts of luffa fruit, 5-12 parts of cinnamon twig, 8-15 parts of angelica root, 8-15 parts of red peony root, 10-20 parts of poria cocos, and 5-10 parts of earthworm.

[0007] The raw materials are in the following weight proportions: 8-12 parts of Sichuan pepper, 12-18 parts of vinegar-processed corydalis rhizome, 12-18 parts of luffa fruit, 6-10 parts of cinnamon twig, 10-12 parts of angelica root, 10-12 parts of red peony root, 12-18 parts of poria cocos, and 6-9 parts of earthworm.

[0008] Secondly, the present invention provides a thermosensitive gel comprising an extract of the aforementioned traditional Chinese medicine composition and a thermosensitive gel matrix; the thermosensitive gel matrix is ​​a mixture of poloxamer 407 and poloxamer 188 in a weight ratio of (15-25):1. This gel is a flowable sol at room temperature (25°C) and rapidly transforms into a semi-solid gel at vaginal ambient temperatures (35-37°C), thereby adhering to mucosal tissue for an extended period and achieving sustained-release drug delivery.

[0009] Thirdly, the present invention provides a drug delivery device, comprising a transparent outer shell, a push rod, and a piston seat. The piston seat is slidably connected to the inner wall of the transparent outer shell, and the push rod is connected to one side of the outer wall of the piston seat. An expansion seat is connected to one side of the outer wall of the transparent outer shell, and a threaded groove is provided on the other side of the outer wall of the transparent outer shell. A threaded seat is threadedly connected to the threaded groove, and a positioning ring is fixedly connected to one side of the inner wall of the threaded seat. An auxiliary mechanism is provided on the other side of the outer wall of the threaded seat. The auxiliary mechanism is a drug delivery head, which is divided into a first base, a second base, a third base, and a fourth base. The first base, the third base, and the fourth base are all conical structures. The second base is an umbrella-shaped expansion structure. A first drug delivery hole is provided on the outer wall of the first base, a second drug delivery hole is provided on the outer wall of the third base, and a third drug delivery hole is provided on the outer wall of the fourth base. The expansion seat is used to increase the gel receiving area, and the threaded groove and threaded seat are used to flexibly switch the drug delivery head.

[0010] Preferably, the expansion seat has a trumpet-shaped opening structure, the positioning ring has an "O"-shaped structure, and the threaded seat has a symmetrically distributed "L"-shaped cross-section.

[0011] Preferably, the first drug delivery port is located at the center of one end of the first base, the second drug delivery port is distributed in a ring array on the outer wall of the third base, and the third drug delivery port is located on one side of the outer wall of the fourth base.

[0012] The outer wall of the threaded seat is base number one, and the gel will only reach the patient's lesion through the first administration port at the center of base number one. The outer wall of the threaded seat is base number two, which allows all the gel to be discharged from base number two, reducing gel residue. The outer wall of the threaded seat is base number three, and the gel will only reach the patient's lesion through the array of second administration ports, allowing the gel to be evenly dispersed for administration. The outer wall of the threaded seat is base number four, and the gel will only reach the patient's lesion through the third administration port. During this process, the patient can axially rotate the transparent shell to move base number four, thereby adjusting the gel administration position.

[0013] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. The herbal composition of this invention uses Sichuan pepper and vinegar-processed corydalis as the principal ingredients to soothe the liver, regulate qi, invigorate blood, and relieve pain; and Liquidambar formosana and Cinnamomum cassia as the assistant ingredients to unblock the meridians and activate collaterals. It is supplemented with Angelica sinensis and Paeonia lactiflora to nourish and invigorate blood, Poria cocos to strengthen the spleen and eliminate dampness, and Pheretima aspergillum to unblock the meridians and guide the medicine. The whole formula closely addresses the pathogenesis of "qi stagnation and blood stasis, and obstruction of the meridians", which is significantly different from the mainstream treatment methods of clearing heat or invigorating qi and removing blood stasis, and provides a new and effective treatment option for clinical practice.

[0014] 2. Traditional Chinese medicine is made into a thermosensitive gel, which utilizes the property of phase transition triggered by body temperature. This solves the problem of short retention time and frequent administration required by traditional vaginal preparations, and significantly improves the bioavailability of drugs and treatment compliance.

[0015] 3. The provided drug delivery device is equipped with a variety of interchangeable drug tips, allowing clinicians to select the most suitable drug delivery mode based on the specific lesion type (deep punctate, diffuse, or localized lateral wall lesions) to achieve precise treatment.

[0016] 4. The combination of the traditional Chinese medicine composition, the thermosensitive gel dosage form, and the multimodal drug delivery device forms a complete solution of targeted drug-long-acting carrier-precise delivery, which is expected to significantly improve the clinical efficacy and quality of life of chronic pelvic inflammatory disease, especially the qi stagnation and blood stasis syndrome. Attached Figure Description

[0017] Figure 1 This is a three-dimensional structural diagram of the drug delivery device in the embodiment; Figure 2 This is a three-dimensional structural diagram of the transparent outer shell, piston seat, and push rod of the drug delivery device in the embodiment. Figure 3This is a top-view sectional view of the drug delivery device in the embodiment; Figure 4 This is a front view sectional three-dimensional structural diagram of the threaded seat and positioning ring of the drug delivery device in the embodiment; Figure 5 This is a three-dimensional structural diagram of the threaded seat and positioning ring of the drug delivery device in the embodiment; Figure 6 This is a three-dimensional cross-sectional view of the auxiliary mechanism of the drug delivery device in the embodiment.

[0018] In the diagram: 1. Transparent outer shell; 2. Piston seat; 3. Push rod; 4. Expansion seat; 5. Threaded groove; 6. Threaded seat; 7. Positioning ring; 8. Auxiliary mechanism; 801. Base No. 1; 802. Base No. 2; 803. Base No. 3; 804. Base No. 4; 805. Drug delivery port No. 1; 806. Drug delivery port No. 2; 807. Drug delivery port No. 3. Detailed Implementation

[0019] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0020] Example 1: Preparation of Traditional Chinese Medicine Composition Weigh the cleaned and selected medicinal materials: 100g of Sichuan pepper, 150g of vinegar-processed corydalis rhizome, 150g of luffa fruit, 80g of cinnamon twig, 120g of angelica root, 120g of red peony root, 150g of poria cocos, and 80g of earthworm. Mix the above eight medicinal materials, add 8 times the amount of purified water, and soak at room temperature for 60 minutes. First, bring to a boil over high heat, then reduce to a simmer and cook for 1.5 hours. Filter the liquid. Add 6 times the amount of water to the dregs again and cook for 1 hour. Filter the liquid again. Combine the two filtrates and filter through a 200-mesh filter cloth to obtain a clear extract. Concentrate the extract under reduced pressure at 65°C to a thick paste with a relative density of 1.25 (measured at 60°C). Add 95% ethanol to the thick paste while stirring until the final ethanol concentration reaches 70%. Refrigerate at 4°C and let stand for 24 hours to allow impurities to fully precipitate. The supernatant was collected and the ethanol was recovered under reduced pressure at 60°C until no alcohol odor remained, yielding an extract. The extract was transferred to a vacuum drying oven and dried at 60°C and -0.09 MPa until the moisture content was below 5%. The extract was then pulverized and passed through an 80-mesh sieve to obtain approximately 152g of a brownish-red, aromatic dry extract of the traditional Chinese medicine composition. The extract was sealed and stored in a cool, dry place for later use.

[0021] Example 2: Preparation of Thermosensitive Gel Take 5.0g of the dry extract powder obtained in Example 1 (based on crude drug weight), 18.0g of poloxamer 407, 1.0g of poloxamer 188, 5.0g of glycerin, and 0.5g of azone, and add purified water to 100.0g. First, dissolve the poloxamer in purified water cooled in an ice bath to swell, then mix the other ingredients evenly, adjust the pH to 4.5-5.5, fill, and sterilize to obtain the final gel. This gel is a free-flowing sol at room temperature (25°C), facilitating transfer from syringes or filling tubes. When the temperature rises to approximately 34-35°C (close to vaginal temperature), a reversible phase transition occurs within 30-60 seconds, transforming it into a semi-solid gel that can adhere to the mucosal surface, achieving sustained drug release.

[0022] Example 3 Drug delivery device Please see Figures 1-6 The device includes a transparent outer shell 1, a push rod 2, and a piston seat 3. The piston seat 2 is slidably connected to the inner wall of the transparent outer shell 1, and the push rod 3 is connected to one side of the outer wall of the piston seat 2. An expansion seat 4 is connected to one side of the outer wall of the transparent outer shell 1, and a threaded groove 5 is provided on the other side of the outer wall of the transparent outer shell 1. A threaded seat 6 is threadedly connected to the threaded groove 5, and a positioning ring 7 is fixedly connected to one side of the inner wall of the threaded seat 6. An auxiliary mechanism 8 is provided on the other side of the outer wall of the threaded seat 6. The auxiliary mechanism 8 is a drug delivery head, which is divided into a first base 801, a second base 802, a third base 803, and a fourth base 804. The first base 801, the third base 803, and the fourth base 804 are all conical structures, and the second base 802 is an umbrella-shaped expansion structure. A first drug delivery hole 805 is provided on the outer wall of the first base 801, a second drug delivery hole 806 is provided on the outer wall of the third base 803, and a third drug delivery hole 807 is provided on the outer wall of the fourth base 804.

[0023] The expansion seat 4 is used to increase the gel receiving area, and the threaded groove 5 and threaded seat 6 are used to flexibly switch the drug delivery head.

[0024] The expansion seat 4 has a trumpet-shaped opening structure, the positioning ring 7 has an "O"-shaped structure, and the threaded seat 6 has a symmetrically distributed "L"-shaped structure. The first drug delivery hole 805 is located at the center of one end of the first base 801, the second drug delivery hole 806 is distributed in a ring array on the outer wall of the third base 803, and the third drug delivery hole 807 is located on one side of the outer wall of the fourth base 804.

[0025] The application method is as follows: Before use, the operator should clean their hands and check that the pre-filled drug delivery unit containing the temperature-sensitive gel from Example 2 is intact and that the push rod 2 slides smoothly. During drug delivery, the patient should lie supine with legs flexed and abducted, and relax their pelvic floor muscles.

[0026] Scenario 1: Drug administration to deep single-point lesions (such as cervicitis) The drug delivery device with base 801 is selected. The operator holds the end of the plunger 2 and slowly and gently inserts the conical base 801 at the front of the device into the vagina to a depth of approximately 6-8 cm, ensuring the tip of the base is close to the external os of the cervix. Then, the plunger 2 is pushed slowly and at a uniform speed. Under the pressure of the piston seat 3, the thermosensitive gel in a sol state inside the transparent shell 1 is precisely ejected in a linear pattern from the drug delivery port 805, directly acting on the target point at the external os of the cervix or deep within the cervical canal. After administration, the gel rapidly transforms into a semi-solid state under body temperature, adhering to the lesion site and achieving a long-lasting effect.

[0027] Scenario 2: Drug administration for diffuse vaginal wall inflammation Select the drug delivery device equipped with base 803. After inserting the device into the vagina at an appropriate depth, push the plunger 2. Under pressure, the sol-gel uniformly seeps out from multiple drug delivery holes 806 arranged in a ring on the surface of base 803, which can widely and evenly cover the entire vaginal wall mucosa surface, making it particularly suitable for treating diffuse inflammation. After the gel phase transition, it can form a protective film of the drug on the entire vaginal wall.

[0028] Scenario 3: Targeted drug delivery for localized lesions on the vaginal wall (such as cysts or inflammation in the lateral fornix). Select the drug delivery device equipped with base 4 (804). Depending on whether the lesion is located on the left or right vaginal wall / fornix, the operator can adjust the orientation of drug delivery port 3 (807) on the side of base 4 (804) by axially rotating the transparent outer shell 1 before or after device insertion, aligning it with the lesion. Pushing the push rod 2 causes the gel to be directionally ejected from drug delivery port 3 (807), directly acting on the target point on the lateral wall. This method achieves precise, non-axial drug delivery.

[0029] Scenario 4: Efficient Drug Delivery and Reduced Residue The drug delivery device is equipped with a second base 802. The second base 802 is made of medical-grade flexible silicone and is shaped like a closed umbrella. When pressure is applied by pushing the push rod 2, the gel overcomes the resistance of the base valve, causing it to expand and deform outwards. The gel is then fully discharged from the gap formed after expansion. This design minimizes the amount of drug remaining in the dead space of the device, ensuring accurate drug dosage and improving utilization.

[0030] After the medication is administered, the threaded seat 6 can be rotated in the opposite direction to separate it from the transparent outer shell 1, making it convenient to clean or replace different medication heads for the next use.

[0031] By flexibly switching between the four types of delivery heads, the drug delivery device provided by this invention can perfectly adapt to the physicochemical properties of the thermosensitive gel prepared in Example 2, and realize diversified and personalized local treatment of pelvic inflammatory disease from "precise targeting" to "broad coverage" and then to "targeted intervention".

[0032] The above description is merely a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. The substitutions may be replacements of some structures, devices, or method steps, or they may be complete technical solutions. Equivalent substitutions or modifications made to the technical solutions and inventive concepts of the present invention should all be covered within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition for the treatment of pelvic inflammatory disease, characterized in that, Made from the following parts by weight of active pharmaceutical ingredient: 5-15 parts of Sichuan pepper, 10-20 parts of vinegar-processed corydalis rhizome, 10-20 parts of luffa fruit, 5-12 parts of cinnamon twig, 8-15 parts of angelica root, 8-15 parts of red peony root, 10-20 parts of poria cocos, and 5-10 parts of earthworm.

2. The traditional Chinese medicine composition for treating pelvic inflammatory disease according to claim 1, characterized in that, The raw materials are in the following weight proportions: 8-12 parts of Sichuan pepper, 12-18 parts of vinegar-processed corydalis rhizome, 12-18 parts of luffa fruit, 6-10 parts of cinnamon twig, 10-12 parts of angelica root, 10-12 parts of red peony root, 12-18 parts of poria cocos, and 6-9 parts of earthworm.

3. A temperature-sensitive gel, characterized in that, The product comprises the traditional Chinese medicine composition of claim 1 and a thermosensitive gel matrix; the thermosensitive gel matrix is ​​a mixture of poloxamer 407 and poloxamer 188 in a weight ratio of (15-25):

1.

4. A drug delivery device, comprising a transparent outer shell (1), a push rod (2), and a piston seat (3), wherein the piston seat (2) is slidably connected to the inner wall of the transparent outer shell (1), and the push rod (3) is connected to one side of the outer wall of the piston seat (2), characterized in that: An expansion seat (4) is connected to one side of the outer wall of the transparent shell (1), and a threaded groove (5) is provided on the other side of the outer wall of the transparent shell (1). A threaded seat (6) is threadedly connected to the threaded groove (5), and a positioning ring (7) is fixedly connected to one side of the inner wall of the threaded seat (6). An auxiliary mechanism (8) is provided on the other side of the outer wall of the threaded seat (6). The auxiliary mechanism (8) is a drug delivery head, which is divided into a first base (801), a second base (802), and a third base. (803) and base number four (804), base number one (801), base number three (803) and base number four (804) are all conical structures, base number two (802) is an umbrella-shaped expansion structure, base number one (805) is opened on the outer wall of base number one (801), base number three (806) is opened on the outer wall of base number three (804), and base number four (807) is opened on the outer wall of base number four (804). The expansion seat (4) is used to expand the gel receiving area, and the threaded groove (5) and threaded seat (6) are used to flexibly switch the drug delivery head.

5. The drug delivery device according to claim 4, characterized in that: The expansion seat (4) has a trumpet-shaped opening structure, the positioning ring (7) has an "O" shaped structure, and the threaded seat (6) has a symmetrically distributed "L" shaped cross-section.

6. The drug delivery device according to claim 5, characterized in that: The first administration port (805) is located at the center of one end of the first base (801), the second administration port (806) is arranged in a ring array on the outer wall of the third base (803), and the third administration port (807) is located on one side of the outer wall of the fourth base (804).

Images