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CN-116782890-B - Patch coated with capsaicin-containing silicone gel

CN116782890BCN 116782890 BCN116782890 BCN 116782890BCN-116782890-B

Abstract

The present invention relates to a patch coated with a capsaicin-containing silicone gel on a substrate, wherein the capsaicin is delivered to the skin in an amount of 0.01 to 0.145g/m 2 , preferably 0.02 to 0.13g/m 2 , more preferably 0.04 to 0.12g/m 2 skin area. The patch has excellent silicone gel adhesion strength in balance with comfort on skin. Furthermore, the invention relates to the use of capsaicin in a patch for balancing the adhesive strength of a silicone gel with the comfort on the skin, and to a method for producing a patch with a silicone gel containing capsaicin.

Inventors

  • ZHOU WENJUAN
  • WANG FAJIE

Assignees

  • 埃肯有机硅（上海）有限公司

Dates

Publication Date
20260505
Application Date
20211228
Priority Date
20201230

Claims (20)

  1. 1. A patch coated with a capsaicin-containing silicone gel on a substrate, wherein the capsaicin is delivered to the skin in an amount in the range of 0.04 to 0.145g/m 2 skin area; Wherein the method comprises the steps of The content of capsaicin in the silicone gel is 0.008 wt% to 0.1wt% based on the total weight of the silicone gel, and the delivery amount is calculated according to the following equation: capsaicin delivery amount (g/m 2 ) =capsaicin amount (%) Coating weight (g/m 2 )/100, and The penetration of the capsaicin-containing silicone gel is in the range of 140-250 mm/10.
  2. 2. The patch of claim 1, wherein the capsaicin is delivered on skin in an amount ranging from 0.04 to 0.13g/m 2 skin area.
  3. 3. The patch of claim 1, wherein the capsaicin is delivered on skin in an amount ranging from 0.04 to 0.12g/m 2 skin area.
  4. 4. The patch of claim 1, wherein the capsaicin is present as a dispersed phase in and in direct contact with and surrounded by the silicone gel matrix.
  5. 5. The patch of claim 1, wherein the capsaicin-containing silicone gel has a penetration in the range of 140-210 mm/10.
  6. 6. A patch according to any one of claims 1 to 5, wherein the capsaicin-coated silicone gel has a coating weight on the skin of from 100g/m 2 to 500g/m 2 .
  7. 7. A patch according to any one of claims 1 to 5, wherein the capsaicin-coated silicone gel has a coating weight on the skin of from 120g/m 2 to 400g/m 2 .
  8. 8. A patch according to any one of claims 1 to 5, wherein the capsaicin-coated silicone gel has a coating weight on skin of from 150g/m 2 to 220g/m 2 .
  9. 9. Patch according to any one of claims 1 to 5, characterized in that the content of capsaicin in the silicone gel is 0.01% to 0.09% by weight, based on the total weight of the silicone gel.
  10. 10. Patch according to any one of claims 1 to 5, characterized in that the content of capsaicin in the silicone gel is 0.02 to 0.08% by weight, based on the total weight of the silicone gel.
  11. 11. The patch according to any one of claims 1 to 5, wherein the silicone gel is formed by a hydrosilylation reaction from a precursor composition comprising, in addition to the capsaicin: 1) At least one organopolysiloxane B comprising: (i) At least two siloxy units of the formula (B1) (Y) a (Z) b SiO (4-(a+b))/2 (B1) Wherein the method comprises the steps of -Y represents a monovalent group containing 2 to 6 carbon atoms and having at least one alkenyl group; -Z represents a monovalent group containing 1 to 20 carbon atoms and not containing an alkenyl group; -a and b represent integers, a being 1, 2 or 3, b being 0, 1 or 2, and (a+b) being 1, 2 or 3; (ii) And optionally further siloxy units of the formula (B2) (Z) c SiO (4-c)/2 (B2) Wherein the method comprises the steps of Z has the same meaning as described in formula (B1), and -C represents an integer of 0,1, 2 or 3; 2) At least one organopolysiloxane CE comprising: Two siloxy end units of the formula (CE-1), identical or different (H) p (R 1 ) q SiO 1/2 (CE-1) Wherein the method comprises the steps of -The symbol R 1 corresponds to C 1 to C 8 alkyl or C 6 to C 10 aryl; -and the symbol H represents a hydrogen atom, wherein p=0 or 1, q=2 or 3 and (p+q) =3; -at least one siloxy group of formula (CE-2): (H) n (R 2 ) m SiO 2/2 (CE-2) Wherein the group R 2 corresponds to a C 1 to C 8 alkyl group or a C 6 to C 10 aryl group, the symbol H represents a hydrogen atom and wherein n=0 or 1, m=1 or 2 and (n+m) =2, and Provided that the organopolysiloxane CE contains two hydrogen atoms per polymer, each hydrogen atom being bonded to a different silicon atom; 3) At least one organopolysiloxane XL comprising: -at least three siloxy units of formula (XL-1): (H) (L) e SiO (3-e)/2 (XL-1) Wherein the symbol H represents a hydrogen atom, the symbol L represents an alkyl group having 1 to 8 carbon atoms (inclusive) or a C 6 to C 10 aryl group, and the symbol e is equal to 0, 1 or 2, and -Optionally further siloxy units of formula (XL-2): (L) g SiO (4-g)/2 (XL-2) Wherein the symbol L represents an alkyl group having from 1 to 8 carbon atoms (inclusive) or a C 6 to C 10 aryl group, and the symbol g is equal to 0,1, 2 or 3, and Provided that organopolysiloxane XL contains 1.0 to 15.0% by weight of Si-H functional groups per polymer, 4) An effective amount of at least one hydrosilylation catalyst E, 5) At least one hydrosilylation reaction inhibitor D, Wherein the molar ratio RHAlk = tH/tAlk < 1.0 or ≡3, wherein tH = mole number of hydrogen atoms directly bonded to silicon atoms of the organopolysiloxane contained in the precursor composition, and tAlk = mole number of alkenyl groups directly bonded to silicon atoms of the organopolysiloxane contained in the precursor composition.
  12. 12. The patch according to claim 11, characterized in that the organopolysiloxane CE contains per polymer two siloxy units of formula (CE-1) where p=1 and at least one siloxy unit of formula (CE-2) where n=0.
  13. 13. The patch of claim 11 wherein organopolysiloxane XL contains 1.5 to 15.0 wt% Si-H functionality/polymer.
  14. 14. The patch of claim 11 wherein organopolysiloxane XL contains 1.5 to 12.5 wt% Si-H functionality/polymer.
  15. 15. The patch of claim 11, wherein the molar ratio RHAlk = tH/tAlk is from 0.4 to 0.9.
  16. 16. The patch of claim 11, wherein the molar ratio RHAlk = tH/tAlk is from 0.5 to 0.85.
  17. 17. The patch of claim 11, wherein the molar ratio RHAlk = tH/tAlk is 3 to 24.
  18. 18. The patch of claim 11, wherein the molar ratio RHAlk = tH/tAlk is 3.5 to 20.
  19. 19. Patch according to claim 11, characterized in that the precursor composition contains a further organopolysiloxane B' comprising only one vinyl or alkenyl group at one end or one terminal siloxy unit in an amount of 1-40% based on the total weight of the precursor composition.
  20. 20. Patch according to claim 11, characterized in that the precursor composition contains a further organopolysiloxane B' comprising only one vinyl or alkenyl group at one end or one terminal siloxy unit in an amount of 1.5-30% based on the total weight of the precursor composition.

Description

Patch coated with capsaicin-containing silicone gel Technical Field The present invention relates to a patch coated with a capsaicin-containing silicone gel and a method for preparing the same. Background Many people suffer from neuropathic pain and it has a destructive impact on quality of life. The causes of neuropathic pain are highly diverse, including reactivation of latent viruses, direct trauma to nerves, diabetes, and HIV infection and treatment. Capsaicin, derivatives and analogs thereof (or the so-called "capsaicinoids (capsaicinoids)") have long been found to be useful in pain relief. Capsaicin (a stimulatory component in capsicum) activates vanilloid receptor (TRPV 1) expressed in nociceptive sensory nerve fibers of the skin, resulting in a severe burning sensation, followed by prolonged function of these nociceptors. For example, US5762963 provides methods and compositions for oral delivery of temporarily increased concentrations of capsaicin or capsaicin-like agents. Wherein the provided composition comprises one or more capsaicin dispersed in a solid carrier material such as lollipop. Although oral capsaicin formulations provide pain relief, there is often unavoidable burning and nausea associated with oral administration of capsaicin or capsaicin-like agents. Furthermore, the oral delivery or oral delivery of capsaicin or capsaicin-like is limited and inconvenient. Various other forms of capsaicin delivery have been developed. One of the most commonly used capsaicin-loaded systems is a self-adhesive matrix based on silicone PSA or rubber or silicone gel. In CN 105687125A, it is disclosed that capsaicin can be added directly to a polydimethylsiloxane-based mixture, which can be applied directly to the skin. In view of patient compliance and convenience, a therapeutic patch coated with a capsaicin-loaded silicone gel is suitable. WO 2005102403 and WO 2008057155 provide silicone gels for adhering transdermal drug delivery devices comprising hydroxy-functional silicone resins to improve adhesion strength. However, when capsaicin is used in patches based primarily on PSA, silicone gel or natural rubber adhesive systems (typically solvent type), the adhesive strength is typically so great that the patient's skin or the object to be adhered may be damaged and cause pain to the patient when removed. In addition they often exhibit cold flow at skin temperatures, which results in a very uncomfortable patient body. There is therefore a continuing need for improvements in PSA, silicone gel or natural rubber, especially silicone gel which addresses the above-mentioned drawbacks in patch applications. Summary of The Invention The inventors of the present application have surprisingly found that the dynamic process of transdermal administration of capsaicin from a patch onto the skin, as measured by the amount of capsaicin delivered, will affect the adhesive strength of the silicone gel and the comfort on the skin. Thus, the above task can be solved by controlling the delivery amount of capsaicin on the skin. More specifically, if the amount of capsaicin delivered in a patch can be controlled in the range of 0.01 to 0.145g/m 2 skin area, a balance between moderate adhesive strength and comfort on the skin will be achieved. The term "delivered amount" as used throughout this application refers to the amount of a pharmaceutically active substance (e.g., capsaicin as used herein) that is transdermally administered from a patch into the skin. The delivery amount may be defined as the amount of active added per unit area of skin contacted with the patch. For example, the capsaicin delivery amount may be calculated according to the following equation: Capsaicin delivery amount (g/m 2) =capsaicin amount (%) coating weight (g/m 2)/100. The present invention therefore relates to a patch coated with a capsaicin-containing silicone gel on a substrate, wherein the capsaicin is delivered to the skin in an amount in the range of 0.01 to 0.145g/m 2. In an advantageous embodiment, the capsaicin-coated silicone gel has a coat weight on the skin of 100g/m 2 to 500g/m 2, such as 120 to 400g/m 2 or 150 to 220g/m 2. In another aspect, the invention relates to the use of capsaicin in a patch for balancing the adhesive strength of silicone gel with the comfort on the skin. In another aspect, the invention relates to a method of preparing a patch having a capsaicin-containing silicone gel. Detailed Description As described above, the present invention relates to a patch coated with a capsaicin-containing silicone gel on a substrate. The term "patch" as used herein is a medical device capable of delivering a drug or active substance by transdermal means and generally refers to a piece of material, particularly an external patch or transdermal patch, which is commonly used in medicine to cover a wound on the skin of a human or animal or to repair a defect on the skin. They are generally prepared by coating, spreading or distributin