Use of a pharmaceutical composition in cheilitis

Abstract

A pharmaceutical composition for the treatment of lip mucosal deformities, comprising triamcinolone acetonide and collagenase, is disclosed. This mixed pharmaceutical formulation is used to correct lip deformities caused by lip mucosal hyperplasia or improper surgery, and can replace surgery for fine-tuning of lip deformities. The mixed pharmaceutical components include: injectable collagenase, triamcinolone acetonide injection solution, and lidocaine hydrochloride injection solution. A 2 ml mixture is prepared by dissolving lyophilized injectable collagenase powder in 2 ml of lidocaine injection solution, followed by the addition of 0.5 ml of triamcinolone acetonide injection solution, resulting in a 2.5 ml collagenase-triamcinolone acetonide-lidocaine mixture. Injection of this mixture into the hyperplastic lip mucosa caused by trauma or improper surgery can dissolve the atrophied lip mucosa, thereby correcting the lip mucosal deformity.

Description

Technical Field

[0001] This invention relates to a novel use of a known substance, and more particularly to a composition which, as an active ingredient, has the effect of dissolving atrophic lip mucosa, thereby correcting lip mucosal deformities caused by trauma or improper surgery. Background Technology

[0002] Acquired vermilion lip deformity is caused by trauma or surgery, resulting in hyperplasia, morphological abnormalities, and asymmetry of the vermilion lip mucosa and / or submucosa. It is occasionally accompanied by functional abnormalities such as speech and salivary control. Distinguished from congenital lip deformities (such as cleft lip and facial cleft), it is a common facial deformity in plastic surgery, and early intervention strategies are relatively mature. For example, early redness-reducing laser combined with triamcinolone acetonide monotherapy or combined injections often achieves good treatment results. However, for mature lip hyperplasia deformities, especially those in the dry lip area, there is still a lack of ideal treatment options clinically. Although existing triamcinolone acetonide combination therapies (such as those combined with 5-fluorouracil, botulinum toxin, or pulsed dye laser) have improved efficacy to some extent, these methods are mostly aimed at early lip hyperplasia deformities with vigorous vascular proliferation and active inflammation. For example, 5-FU focuses on inhibiting early fibroblast proliferation; botulinum toxin mainly promotes recovery by reducing tension and inhibiting TGF-β1 expression; and laser targets excessive microvascular proliferation. The above methods are often ineffective for late-stage lip hyperplasia malformations (stable-stage malformations) whose main pathological feature is highly cross-linked collagen.

[0003] For mature lip hyperplasia, especially mucosal hyperplasia in the vermilion border, if the hyperplasia is located in the moist lip area, it can be excised through a relatively concealed incision. However, for deformities in the dry lip area, current clinical interventions are limited, and surgical excision of the hyperplasia is the only option. This often leaves secondary lip scarring and deformities in the dry lip area. Summary of the Invention

[0004] One object of the present invention is to provide the use of a pharmaceutical composition in the preparation of a medicament for the treatment of lip mucosal deformity correction.

[0005] Another object of the present invention is to provide the use of a pharmaceutical composition in the preparation of a medical device for the treatment of lip mucosal deformity correction.

[0006] Clinically, triamcinolone acetonide (TAC) has some efficacy in treating atrophic subcutaneous tissue, but its effect on degrading old collagen composed of highly cross-linked fibers already formed in the tissue is relatively weak. Collagenase, by specifically degrading deposited abnormal collagen fibers, has been widely used in the release treatment of intervertebral disc herniation and contracture scars. Based on these theoretical foundations, we have combined triamcinolone acetonide with collagenase in clinical practice and found that when the two are mixed and injected at a ratio of 1:4, the treatment effect on lip mucosal hyperplasia is significant, avoiding the risk of secondary surgical intervention and filling a gap in this field.

[0007] The collagenase used in this invention belongs to the metalloproteinase class and can specifically hydrolyze type I and type III collagen. By degrading old collagen fibers, it directly loosens tissue contractures, thereby improving the hardness and smoothness of lip mucosal deformities. While TAC inhibits new collagen synthesis, its more crucial role is to reduce the level of collagenase inhibitors (such as α2-macroglobulin and α1-antitrypsin) in the tissue, thereby indirectly enhancing the biological activity of both endogenous and exogenous collagenases. The combined use of these two agents, through a complementary mechanism of "inhibiting synthesis + promoting degradation," significantly improves the therapeutic efficacy for lip mucosal deformities.

[0008] The pharmaceutical composition of the present invention comprises triamcinolone acetonide and collagenase, which are used as active ingredients in the preparation of a medicament for treating lip mucosal deformities.

[0009] The compounds of this invention are further mixed with the excipient lidocaine hydrochloride to prepare a drug (formulation) for treating lip mucosal deformities. For example, triamcinolone acetonide injection and lidocaine injection are mixed at a volume ratio of 1:4.

[0010] Dissolve 600 units of collagenase powder for injection thoroughly in 2 mL of 20 mg / mL lidocaine injection solution, and then mix with 0.5 mL of 40 mg / mL triamcinolone injection solution to form a preparation with a triamcinolone to collagenase solution volume ratio of 1:4.

[0011] Drug-containing medical devices combining drugs and medical devices are already quite common, such as dressings containing triamcinolone acetonide and collagenase. In this invention, triamcinolone acetonide and collagenase are also loaded or coated as active ingredients onto a scaffold material for the manufacture of medical devices treating lip mucosal deformities. Common scaffold materials include PLA, PLGA, PGA, GelMA, silicone, and metals. They can also be mixed with biocompatible biodegradable materials to form microneedles and microneedle arrays, or loaded into metal microneedles to create microneedle chips. When the microneedles pierce the skin, they release triamcinolone acetonide and collagenase. Attached Figure Description

[0012] Figure 1 A schematic diagram illustrating the pharmaceutical composition of the present invention;

[0013] Figure 2 Photographs showing changes in lip mucosal deformity in a patient before and after administration of the pharmaceutical composition of the present invention;

[0014] Figure 3 Photographs showing changes in lip mucosal deformity before and after administration of the pharmaceutical composition of the present invention to another patient;

[0015] Figure 4 Photographs showing changes in lip mucosal deformity before and after administration of the pharmaceutical composition of the present invention to another patient;

[0016] Figure 5 Photographs showing changes in lip mucosal deformity before and after administration of the pharmaceutical composition of the present invention to another patient. Detailed Implementation

[0017] The technical solution of the present invention will be described in detail below with reference to the accompanying drawings. The embodiments of the present invention are only used to illustrate the technical solution of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solution of the invention without departing from the spirit and scope of the technical solution of the present invention, and all such modifications and substitutions should be covered within the scope of the claims of the present invention.

[0018] Patients meeting the inclusion criteria (those with deformities following old lip trauma or postoperative asymmetry of the lip) were treated. 600 units of injectable collagenase powder (Shanghai JOY Biopharm. Co., Ltd, China) were thoroughly dissolved in 2 mL of 20 mg / mL lidocaine injection solution (Tiansheng Pharmaceutical Group Co., Ltd, China), followed by the addition of 0.5 mL of triamcinolone acetonide injection solution (Kunming Jida Pharmaceutical Co., Ltd, China), and mixed thoroughly to achieve a triamcinolone acetonide to collagenase solution volume ratio of 1:4. The mixture was transferred to a 1 mL fine syringe and connected to a 30G needle. Before injection, the needle was bent so that the needle tip formed an angle of approximately 110° with the longitudinal axis of the syringe, with the bevel of the needle tip facing upwards. The needle was inserted close to the plane of the skin and the deformed mucosa, penetrating the superficial layer of the deformed mucosa, avoiding excessive needle depth which could lead to submucosal tissue atrophy. The injection dosage is determined based on the size of the mucosal malformation. Generally, the medication should be injected thoroughly until it covers the entire protruding area and the surface turns white. Repeat the injection every 4 weeks until the malformed mucosa is flush with the surrounding mucosa and no longer protrudes, or until two consecutive injections show no significant improvement. Follow-up should be conducted every 4 weeks after injection for clinical evaluation and photographic documentation. (Injection diagram) Figure 1 As shown.

[0019] Case 1: A 45-year-old woman, who had undergone upper lip M-shaped lip and lower lip petal lip augmentation in Japan four years prior, felt that her upper lip philtrum and lower lip lateral philtrum were too prominent and requested surgical removal. After one treatment with the drug of this invention via tissue injection, the upper lip philtrum and lower lip lateral philtrum significantly decreased in size, and the patient expressed great satisfaction. (See also...) Figure 2 )

[0020] Case 2: A 25-year-old woman presented with dry lip mucosal hyperplasia and deformity after trauma. After five sessions of tissue injection therapy, her lip deformity significantly improved, and the patient was very satisfied. (See also...) Figure 3 )

[0021] Case 3: A 29-year-old male, three months after undergoing upper and lower lip thinning surgery, felt his upper lip's philtrum was too pointed. After one injection of the drug of this invention into the tissue, his upper lip's philtrum flattened within a month, and the patient expressed great satisfaction. (See also...) Figure 4 )

[0022] Case 4: A 42-year-old woman, three years after undergoing upper lip deformity correction surgery, complained of asymmetry and localized protrusion of the mucosa at the caruncle of her upper lip and requested minimally invasive treatment. One month after receiving a single tissue injection of the drug of this invention, the protrusion of the upper lip caruncle mucosa significantly improved, and the patient expressed great satisfaction. (See also...) Figure 5 )

Claims

1. The use of a pharmaceutical composition in the preparation of a treatment for lip mucosal deformities, characterized in that... Including triamcinolone and collagenase.

2. The application according to claim 1, characterized in that... It also includes lidocaine.

3. The application according to claim 1, characterized in that... The collagenase is dissolved in lidocaine injection solution and then mixed with triamcinolone injection solution.

4. The application according to claim 3, characterized in that... The collagenase was added at 600 units.

5. The application according to claim 3, characterized in that... The lidocaine injection solution is 2 mL, 20 mg / mL.

6. The application according to claim 3, characterized in that... The triamcinolone acetonide injection solution is 0.5 mL, 40 mg / mL.

7. A pharmaceutical composition, characterized in that... It includes triamcinolone acetonide injection, lidocaine injection, and collagenase, wherein the collagenase is added at 600 units.

8. The pharmaceutical composition according to claim 7, characterized in that... The triamcinolone acetonide injection solution was 0.5 mL.

9. The application according to claim 1, characterized in that... The lidocaine injection solution is 2 mL.

10. A medical device, characterized in that... Includes the pharmaceutical composition of claim 7.

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